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BINOCULAR VISION & STRABISMUS QUARTERLY (ISSN 1088-6281), the "loftiest scientific journal in the world"is published at an altitude of 9100 feet above sea level, in the shadow of the Continental Divide, in SummitCounty, Colorado, by BINOCULUS PUBLISHING, PO Box 3727, 740 Piney Acres Circle, Dillon CO 80435-3727USA; Tel and FAX 970-262-0753. A Medical Scientific E-Periodical. Webmaster: Justin Patnode, Webez.netInternet Services, Dillon, Colorado. Official publication date January 1, 2007.

COPYRIGHT 2007. All rights reserved. No part of this publication may be reproduced or transmitted in any formor by any means, electronic or mechanical, including xerographic copy, photocopy, recording, or an informationstorage and retrieval system, without permission in writing from the publisher.

EDITORIAL OFFICE / MANUSCRIPTS: Please send to the Editor, Binocular Vision & Strabismus Quarterly, PO Box3727, 740 Piney Acres Circle, Dillon CO 80435-3727 USA. Please see and use "Instructions for Authors",pages 10-11. Letters to the Editor are considered "for publication" unless otherwise indicated and may beedited and condensed as space dictates.

ADVERTISING: Please direct inquiries to BINOCULUS PUBLISHING, PO Box 3727, 740 Piney Acres Circle, Dillon CO 80435-3727 USA. Tel & FAX 970-262-0753. Media kit andrates on request.

SUBSCRIPTIONS: Per four issue annual volume only: Individual: $68 a year for a three year subscription ($ 204=3x68),$78 a year for a two year subscription ($ 156 =2x78), $84 for a one year subscription. Institutions and Libraries: $94 a year for a three year subscription ($ 282 =3x94), $110 a year for a two yearsubscription ($ 220 =2x110), $120 for a one year subscription.........Single issues and back copies $28. Pleasesend orders with check or money order payable in US $ funds to Binoculus Publishing, PO Box 3727, 740Piney Acres Circle, Dillon CO 80435-3727 USA. Visa, Mastercard and American Express charges gladlyaccepted, especially for International orders. Bound Volumes also available to subscribers. To subscribe ororder, Call/Fax 970-262-0753.

Disclaimer: The ideas/opinions expressed in Binocular Vision & Strabismus Quarterly do not necessarily reflectthose of the publisher or editorial staff. BV&Sq makes every effort to maintain accuracy; however, cannotguarantee accuracy of contents or claims of advertisers. The reader should consult the maker ormanufacturer's instructions before using any product appearing in BV&Sq.

The designation of individual issues is by the quarter, not the season, because seasons are never the same,but opposite, in the Northern and Southern hemispheres. The seasons are however designated on the coverwith the Northern season on the top and, inverted below, the current season in the Southern hemisphere.

Bin ocula r Vis ion & S trab ism us Qu arte rly© EDITORIAL BOARD First Quarter of 2007, Vo lume 22 (No.1): PAGE 2

Leonard AptRobert W. ArnoldE.S. Avetisov, RussiaJohn D. BakerP. Vital Berard, FranceFrank Billson, AustraliaMichael C. BrodskyJorge A. Caldeira, BrazilAlberto O. Ciancia, ArgentinaKenneth J. CiuffredaDavid K. CoatsJeffrey CooperJan-T H.N. de Faber, NetherlandsJay M. EnochCaleb GonzalezMichael H. Graf, GermanyDavid GuytonEugene M. HelvestonRichard W. HertleCreig S. HoytDavid G. HunterEdouard Khawam, LebanonLionel Kowal, Australia

Stephen P. Kraft, CanadaKrystyna Krzystkowa, PolandJoseph Lang, SwitzerlandMalcolm L. MazowHenry S. MetzJoel MillerJames L. Mims IIIScott E. OlitskyGian Paolo Paliaga, ItalyEvelyn A. PaysseZane F. PollardJulio Prieto-Diaz, ArgentinaEdward L. RaabMichael X. RepkaJames D. ReynoldsDavid L. Romero-Apis, MexicoAlan B. ScottKurt SimonsAnnette Spielmann, FranceDavid R. Stager, Sr.Martin J. Steinbach, CanadaDavid S.I. Taylor, EnglandGuillermo Velez, ColombiaBruce C. Wick

M. Edward Wilson, Jr.Kenneth W. Wright

EMERITUS

Shinobu Awaya, Japan

Henderson Almeida, Brazil

Bruno Bagolini, Italy

Albert W. Biglan

William N. Clarke, Canada

John S. Crawford†

Robert A. Crone,

Netherlands

Eugene R. Folk†

David A. Hiles

David Hubel

Bela Julesz

Herbert Kaufmann, Germany

Philip Knapp†

Burton J. Kushner

Pinhas Nemet, Israel

J.V. Plenty, United Kingdom

Robert D. Reinecke

William E. Scott

R. Lawrence Tychsen

INDEX TO ADVERTISERS, VOLUME 22, NUMBER 1, 2007

Fresnel Prism and Lens Co. Page 1 (front cover)Burton J. Kushner's Grand Rounds Collection Pages 4-5

Gunter K. von Noorden's History of Strabismology Pages 4-5

Eugene M. Helveston's Surgical Management of Strabismus Pages 4-5

British, Irish and American Orthoptic Journals Page 13

“... the belief that one’s view of reality is the only reality is the most dangerous of all delusions ...”-Watzlawick, 1976

EDITOR ISSN 1088-6281 First Quarter of 2007Paul E. Romano, M.D., M.S.O TABLE OF CONTENTS Volume 22, Number 1

MEDLINE Abbr. Binocul Vis Strabismus Q NLM ID: 9607281

6 The History of “Binocular Vision and Strabismus Quarterly©”10 Advice and Information for Authors11 Brian D. Stidham, M.D., Memorial Lectureship12 2007 Meeting Calendar14 People and Places; News and Announcements

15 EDITORIAL: Here We Go, Charging Full Throttle and Headlong Into the Internet.“Binocular Vision and Strabismus Quarterly© ”Stops the Presses! All But Totally and Re-Establishes Its Old Website at

BINOCULARVISION.NET for Continuing E-Publication of this Now E-Periodical

Paul E. Romano, M.D., M.S. Ophthalmology

*** ORIGINAL SCIENTIFIC ARTICLES ***

17 Relative Scotomata in the “Normal” Eye of Functionally Amblyopic Patients. A Scanning Laser Ophthalmoscope (SLO) Microperimetric Study

David A. Johnson, M.D., Ph.D.

49 Long Term Vision Outcomes of Conventional Treatment of Strabismic and Anisometropic Functional Amblyopia

Pam Garoufalis, BOrth(Hons), Zoran Georgievski, BAppScOrth(Hons) and Konstandina Koklanis, Ph.D.

*** MEETING REPORT ***

57 Strabology Report of the 2nd Pediatric Ophthalmology and Strabismus Day:An Extravaganza in Las Vegas, November 2006Meeting Organized and Directed by Kenneth Wright, M.D.

Meeting Reported by Sonal Farzavandi, FRCS

BINOCULAR VISION & STRABISMUS QUARTERLY©The First and Original International Scientific Periodical devoted to

Strabismus and AmblyopiaCited Online in MEDLINE and EMBASE; Cited in INDEX MEDICUS and INDEX BINOCULUS

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(all subscriptions, USA and International) for3 years 2007-2009 @ $ 68/yr = $204 O2 years 2007-2008 @ $ 78/yr = $156 O1 year 2007 @ $ 84/yr = $ 84 O

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von Noorden: History Strabismology O $ 179 O $ 159Helveston: Surg Mgmt Strabismus, ed 5 O $ 179 O $ 139Kushner: Collection BV Grand Rounds O $ 149 O $ 89

Subscriber Savings (total for all 3) ($120)

Please enter my LIBRARY/INSTITUTIONAL electronic subscription

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LIBRARY and INSTITUTIONAL NOT BV&SQ YES BV&SQBOOKS: Please send _____ copy(s) of subscriber subscriber

von Noorden: History Strabismology O $ 289 O $ 229Helveston: Surg Mgmt Strabismus, ed 5 O $ 289 O $ 229Kushner: Collection BV Grand Rounds O $ 289 O $ 189

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Binocular Vision & A H istory of Bin ocular Vis ion Qu arte rly First Quarter of 2007Stra bism us Qu arte rly© Vo lum e 22 (No .1):An eye medical scientif ic e-periodi ical Pa ges 6-9

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A History of this scientific periodical, Binocular Vision & Strabismus Quarterly.A Celebration of Our 20th Anniversary

The year was 1984. Parks’sub-specialty ofpediatric ophthalmology, which had absorbed thepreviously free standing, but much less marketablesubspecialty of ocular motility/strabology, in theUnited States, for sure, was growing rapidly. Thiswas the era before managed care intruded. It wasthe very last of the good years to be a physicianand/or an academician.

Our sole suspecialty periodical was the Journalof Pediatric Ophthalmology and Strabismus which hadbeen founded as the Journal of Pediatric Ophthal-mology (only) by Editor Samuel V. Abraham in1964 (the very first year your Editor started hisophthalmology training!). With the advent of theAmerican Association for Pediatric Ophthalmology(and [later] strabismus) in the early '70's it was nowfully owned by its New Jersey publisher, Slack.With the requirement of submission of all papersfrom the annual AAPOS meetings, the waitingtime in 1984 for publication of an article in theJPOS was two and a half years! Even though thejournal was subsidized by the AAPOS, Slackwould not enlarge the journal enough or even at allto handle this demand, in spite of significant profitsfrom the journal. No solution to this dilemma wasapparent from Slack, or elsewhere.

At that time your founding editor (FE) wasrunning the Pediatric Ophthalmology and Strabis-mus Service at the University of Florida in Gaines-ville. Another member of the faculty there, FrankPollack, who ran the Cornea Service, had recentlystarted a new journal entitled "Cornea" with thehelp of the American, New York, arm of theFrench publisher, Masson. At a departmental party at his home, he proudlyshowed us his new computer and office for runninghis journal. Realizing that our subspecialty couldcertainly use some help with regard to publishingthat backlog of 2 ½ years for the JPOS, we men-tioned our problem to Pollack. He said he wouldtalk to Pierre LaHaye, at Masson in New York,who was in charge of the eye journals. Pierre said they were very interested in anothereye subspecial ty journal . We agreed onundertaking the job of assembling an EditorialBoard and soliciting articles as the first Editor. Itdidn't take long to put together an outstanding,large, inter-national Editorial Board. AlbertoCiancia and Joseph Lang were especially helpful.Everyone agreed it was a good idea. Only my oldmentors refused an invitation to join the Ed Board!(I guess taking a job working for a former studentis not a high priority!) They still thought it was agood idea. Excellent scientific articles werequickly volun-teered by many Ed Board members.We started putting the first issue together with thehelp of Alvin Fayman who was to be ourproduction manager at Masson.

Only one person in our professional communityobjected to BVQ, because he thought we werealready publishing enough articles about strabis-mus and he didn't want to read any more. He wroteto our entire professional community in an effort tostop our efforts, but no one seconded his singularsentiments.

We titled the journal "Binocular Vision" be-cause BV is what the study and treatment ofstrabismus is really all about. “BV” is also the firstterm of the title of our mentor von Noorden'sesteemed textbook "Bible", so it had to be OK. "BV", we intended, would compliment and fit inwith the "JPOS", both literally and figuratively. Itwould not sound like a direct competitive threat -which too many of our associates were all tooready to assume anyway! To be sure, we further staked out our strabologyarea by adding as a subtitle "eye movements,strabismus, and amblyopia". We called it a "quarterly", because that was ourintended publication schedule for starting, andbecause we think the name of a periodical, when ittakes a common term for a title, needs to haveanother word in the title so the periodical is notconfused with, and does not have to be additionallyseparated from, the clinical item; (i.e., when yourefer to periodicals like Ophthalmology or Retina orCornea, don't you often find yourself adding, "thejournal" so your listener knows that you arereferring to a periodical and not to a piece ofanatomy or a science? But "journal" is only Frenchfor "daily", so we called it "Quarterly" which ittruly is).

In early 1985 as the first issue was about to goto press, in April, Masson suddenly decided to closeits American branch and sell all of its scientificperiodicals, "lock, stock and barrel", to RavenPress in New York. (We suddenly felt like aprofessional athlete getting "traded" without choiceor input.) The President/owner of Raven Press, Dr.Alan Edelson, PhD, invited us to journey to theirNew York offices to discuss the future of BVQ withhim. On arrival, Edelson first told us that TomFrance, then President of the AAPOS, had justvisited him only the day before seeking a publisher toreplace Slack, who would not permit the neededexpansion of the JPOS. Edelson suggested that France and the AAPOSand we could and should combine the twopublications into one Raven publication. Tom and I presented this idea to both of ourEditorial Boards. But our board members weremost enthusiastic about having a separate journaldevoted specifically to strabismus and binocularvision and only by remaining separate could we doso. Nor did sharing their journal with us go over

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very well with Tom France, the JPOS Editorialstaff, or the AAPOS. That left Dr. Edelson and Raven with just us,BVQ. Edelson said that BVQ did not justify hisefforts financially. Since BVQ had not even printedits first issue yet, Edelson felt no obligation to me,BVQ, or its Editorial Board members. Therefore, hesaid, that he would not publish BVQ but ratherwould simply abandon/cancel BVQ and just let usdie, evaporate or whatever. Neither I nor our Editorial Board liked that atall. After further discussions Dr. Edelson agreed to"give" the ownership and rights to BVQ to your FE.He said we could try to publish it ourselves, on ourown. We had to contractually agree to do it all byourselves and not seek or use the assistance of, orsell BVQ to, any (other) publishing house for atleast five years. So we became owner and publisher as well asthe Editor.

The first major hurdle was to get the OK of ourboss, the University of Florida OphthalmologyProfessor and Chairman who was himself!, withhis wife, a medical publisher (Triad Publishing,Gaine-sville). Fortunately, our non competecontract with Raven would not allow him torequire that BVQ be published by his company,Triad.

We found a local printer in town, Ewing Press,who printed the football programs for the Uni-versity of Florida football program, (Go Gator!s)and with the help of a free lance local typesetter weset about publishing the journal. Your FE did theold cut and paste wax layout routine.[Can you re-member that?!] The first issue was actuallycompleted, printed and mailed out near the end of1985. Volume 1 was initially called "1985"because we still had high hopes of somehowmaking that year our first full year of publication.However, that was not to be and the first full yearof the journal was actually 1986, denoted Vol. 1,"1985-1986".

Within that first year we were also to have thefirst of many recurring changes with printers.Ewing Press was bought out by another localprinter, Marsh, and we had to break in another setof layout, typesetters and press operators. Volume 2 was then calendar year 1987. In 1988(Volume 3), half way through it our printer, Mr.Marsh, passed away and the firm closed down. Wethen went to our third local Gainesville printer inthree years, Storter.

In early 1989, after leaving UF, and thanks tocomputers we took over in house production ofBVQ. Fortunately, "desktop publishing" on compu-ters had just reached the point where one did nothave to be a computer engineer-whiz to do it. So we plunged in full time, purchasing a 286-12! desktop (for about $1800!) and an HP LaserPrinter (for another $1400!), which, believe it or

not, has just been retired after 14 years of servicealthough it has required repair from time to time.Unbelievably? that printer also had about 100,000road miles on it as we trucked it back and forthbetween Florida and Colorado every 3 months forfive years (until we moved here in 1995). Wecertainly have seen a number of computers (?12+)come and go, and almost as many copy and faxmachines as well during this same 14 year period.But we still use our original word processingsoftware WordPerfect 5.0 because that is all weneeded then and now. Your FE, because of his ancient artistic bent,(alternate careers at one point were architectureand industrial or automotive design) continued asthe layout man and became also the typesetterwhile his "better half" became chief typist as wellas both the managing editor and the businessmanager, which included doing just about every-thing else except the printing. She is in fact really"the publisher." We learned a lot and fast. In those days, it tooktwo months of our time, truly full time, both of us,to turn out each issue. That gave us a few weeks tobreath and catch up on other things in betweenissues. (We have gotten a lot quicker at it, but itstill takes the better part of a month.) At the end of 1989, Storter decided theysuddenly needed a lot more of our money just toprint the journal since we were no longer payingthem for layout and typesetting. So we searched foranother printer which we finally found down inKissimmee, (near Orlando), Cody Publications,who was at that time all periodicals. They weregreat, printing 50 or 60 commercial publications

Also that Spring, on recommendation, wetraveled to Washington DC to personally talk to thepeople at the National Library of Medicine aboutgetting into Index Medicus. It was already longerthat we thought it should have been but we weresoon to find our expectations not rapidly fulfilled.Nor did our visit to NIH seem to help at all, in spiteof our attempt to play Washington politics. Maybe, we thought, a more impressive titlewould help, so we became Binocular Vision & EyeMuscle Surgery thinking that "surgery" in the titlemight be a key to entry to the NLM as we couldclaim to be the only journal devoted to strabismusSURGERY.

Just a year later, in 1991, Mr. Cody retired andclosed his printing business. One of his salesmen,a Mr. Willis, opened his own company and tried toservice Cody's customers. However, as good as hewas as a salesman, he was not a good printer'sagent and after a couple of difficult issues, weagain sought printing elsewhere. This time we found it in the F.M.A., the FloridaMedical Association. We turned to their printer inJacksonville, Centurion Press. They did a nice jobon the monthly Florida Medical Journal and they dida nice job for us. But, once again, after just a fewgood years the Florida Medical Society, which had

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created Centurion Press to print their journal,closed it, and turned the printing of its journal overto a major foreign source. [early out-sourcing!]Some employees at Centurion, who had been mosthelpful to us, found themselves new printing jobsand us too a new, and our current, printer,Economy Printing, Jacksonville. We have beenwith them ever since even though we are nowretired to Colorado. Fed Ex and UPS and faxesmake it easy.

In 1995, following the introduction of aEuropean journal entitled simply Strabismus twoyears earlier, we felt our colleagues could hardlyaccuse us of threatening them anymore andreplaced the "Surgery" in our title to become whatwe still are today, Binocular Vision and Strabismus

Quarterly. We also finally officiallyretired from Florida and clinicalpractice, to the Rocky Mountains.

The last major chapter in ourhistory to date, was our admission,finally, after 14 years, to Medlineand Index Medicus in the middle of1998. This was followed almostimmediately by admission to Ex-cerpta Medica and EM Base. Thiswas at least largely the result of thegood offices of BV&SQ EditorialBoard members Larry Tychsen andDavid Guyton. [For the most complete index,however, of what has appeared inBVQ over the past 17 years, in-cluding the dozen before we madethe NLM grade we still composeand publish our own Index Binoc-ulus. We shall continue to do sobecause the NLM is only interestedin indexing scientific articles, andonly according to the relativelygeneral (for us) MESH keywords.A great deal of the material in BVQsuch as meeting reports, book re-views, news, and editorial followuptype material is therefore not NLMindexed. Index Binoculus also indexesscientific articles with more de-tailed and specific terms thanMESH, facilitating your retrieval ofinformation.]

Last year in the first issue of2002, we updated and wrote here: "Now in 2002, we enter yetanother phase. A combination of events hascontributed: 1. This "mom and pop" operation,successful for 17 years, is finding itharder and harder to keep up withthe latest advances in the use ofcomputers, (no thanks to Bill [the

fraud] Gates) and the new on line services providedby large publishers.2. There have been in the last two years, severalexciting medical problems for your editor, whichhave left him fortunately unimpaired but whichhave made him realize that he's not going to bearound forever, and it is time to look for apermanent home for BV&SQ, while I am still able todo so.3. The journal has enjoyed cooperative efforts ofco-promotion with Swets & Zeitlinger, the Dutchpublisher of Strabismus. Now they are interested inmerging the two journals in the near future. Keep being a subscriber, but keep tuned forfuture events!

(Continued on next page)

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Update 2003: Well, it (2002) was an excitingyear but it didn't turn out quite as we had intendedor hoped. We have described some of thosehappenings in detail already in these pages [SeeBV&SQ 17(2):76 and 17(4):278] 1. Long time Charter Editorial Board memberand [former] friend Carlos Souza-Dias, as outgoingPrexy of the ISA, cleverly blocked our wellplanned proposal for a combined BV&SQ andStrabisnus to become the permanent ISA journalbecause he thought $49 a year (fantastic price Inegotiated with S&Z) for one merged journalwhich combined two journals currently costing$84 + $126 = $210 per year -that this was a NOTa reasonable price for ISA members, who werealready being taxed about $75 per person per yearto pay for fellowships for non ISA members! 2. John Martin, the new head of Publisher Swetsand Zeitlinger had so much trouble managingHuibert Simonsz, the Editor of his S&Z"Strabismus" Journal, that he changed his mind andupped (insisted upon) his requirement for personaltotal 100% Editorial control of the merged journal,in spite of the fact that nowhere in the scientificpublishing world is this done by anyone. No M.D.was happy with that. 3. The S&Z Board, in spite of the fact that theywould more than double or triple their profit bybuying BV&SQ, reneged totally on previouslydiscussed offers for BV&SQ. They limited theirfinal offer initially to only one sixth and thenfinally to only one third of what they had offered inpreliminary discussions. I had been warned ofDutch businessmen but this was the biggest fraudthat this publisher has ever been subjected to byanyone. [P.S. except Bill Gates, of course]

Some unintended consequences of these eventswere enumerated in last issue's lead editorial. Chiefamong these is Editor Burt Kushner, after 17 yearsand 68 cases of his superb strabismus "GrandRounds", deciding to move on to other majorprojects since he too has not yet found the fountainof youth, and after almost two decades wishes tomove on to other projects. We plan to publish in abook, all 68 of these articles. Fortunately your Editor in Chief's repairedmitral valve is doing OK, and his ventriculartachycardia has not returned, and his retinas remainattached, so we can continue on for the present aswe were. Thanks to a peculiar accommodation ofone of our variable annuity investments, when I dofinally kick the bucket, there will be enough breadavailable to set up a foundation to support anindependent BV&SQ permanently. In the meantime we are refreshing the EditorialBoard with some new and younger faces, whomwe hope will help to see that the foundation doesits job, forever.

-PEROriginally published in BV&SQ 2000; 15(1):6-7.Revised and updated 2003; 18(1):4-6

Update BV&SQ 2005; 20(1): 4-6

Since the last printing of this history two yearsago, with the help of Marcia Youngdahl, owner ofour local print shop, we did get that book of BurtKushner's 68 editions of his Grand Roundspublished last year .We were all quite happy withthe way it turned out. We did the best we could tocopy the gorgeous cover style of Jean PaulWayenborgh's History of Ophthalmology, but in arich red rather than his royal blue.

Everything else continues unchanged in thelives of your FE and his publisher-orthoptist-wife.She put out Burt's book virtually single handed lastyear. [P.S. But who would have thought that Slackwould continue publishing the JPOS, or that somany AAPOS members would be so willing tohelp them do so considering how poorly theytreated the AAPOS and its membership for allthose years? Who would have thought we couldhave not just one but FOUR scientific periodicalsservicing our subspecialty — and surviving?]

Amazingly this is our twentieth volume and ourtwentieth year of publication. We plan to celebratethe completion of our twentieth year during theannual AAPOS meeting about this time next year,which will be held just five miles from our homeand offices, up the road at the Keystone ski resort.

-PER

Update 2007 BV&SQ 22(1)

That 2006 AAPOS meeting next door wasmost successful but our 9500 foot altitude was notwell tolerated by too many participants (see Dr.Mims III’s report published in our pages in the Q2summer issue page 102) so a repeat is not likely.There are, however, many good ski resortsavailable in the more comfortable 8000 or so footrange like our neighbor Vail.

At that meeting I found out that our recentmyopia collaborator-contributor Michael Chiangwas limiting his periodical subscriptions to thoseavailable on the internet. That did start us thinkingabout what you see culminating, thanks to a host offactors, including many advantages, in this firstissue for 2007 conversion to an electronic internetversion (see Editorial in this issue on followingpages 15-16).

-PER

BINOCULAR VISION & Strabismus Quarterly: INSTRUCTIONS FOR AUTHORS

SUBMISSION OF MANUSCRIPTS (TYPESCRIPTS)

Electronic Submission: Send one copy of your Letter oftransmittal, copyright transfer, and permissions for publicationsof photos (see below for details of these), and one copy of yourpaper/manuscript, using a word processing program forMicrosoft/ Office typed in a loose typewriter typeface, anddouble-spaced. Include all Tables and Figures (graphs, linedrawings, and photos) preferably as part of the manuscriptrather than as attachments. to: [email protected]

Standard Hardcopy Submission: Send four (4) copies, typedin a loose typewriter typeface, and double-spaced withxerographic copies of all figures (graphs, line drawings, andphotos). Also send two (2) originals of all computergenerated/printed figures and glossy photo prints of and figureby EITHER US Post Office or a delivery service TO:EDITOR, BINOCULAR VISION

740 PINEY ACRES CIRCLE PO BOX 3727DILLON CO 80435-3727 USA

Please also send a CD or 3.5" diskette copy of your manuscriptmade on an IBM or IBM compatible PC using Word Perfect 10or Microsoft word processing program.EITHER WAY- Send acovering letter of transmittal with name, address, telephoneand FAX numbers, email address of corresponding author,i.e.,the author to whom letters of receipt and acceptance, galleyproofs and reprint request forms are to be sent.Note: To comply with the Copyright Act of 1976, include also thefollowing COPYRIGHT TRANSFER STATEMENT, signed byeach and all authors: "The undersigned author(s) transfers allcopyright ownership of the manuscript entitled (title of article)to Binocular Vision & Strabismus Quarterly/BinoculusPublishing in the event the work is published. The author(s)warrants that the article is original, is not under considerationby another journal, and has not been previously published".

References: If "PERSONAL COMMUNICATIONS", majoramounts of text or any Figures from any previously publishedpaper are included in your paper, include also reprintpermissions from prior author and publisher if printed. (see"Sources, Credits, and Permits", below).All manuscripts, including solicited material, is subject toeditorial review and revision. Only manuscripts in English areconsidered. All Manuscripts submitted become the property ofthe Journal and may not be published elsewhere withoutwritten permission from both this Editor and Publisher. There are no publication or "page" charges to authors except forillustrations or printed length in excess of 12 pages. But nocharges are levied without consent of the corresponding author.

TEXT STYLE AND CONTENTPage Headers Each and every page, including xerographicfigure copies, Legends for Figures, Tables and References,should be arabic numbered consecutively with an abbreviatedtitle but NO authors' names at the page top. The Title page ispage 1, ABSTRACT is page 2.Title Page: Declarative titles are acceptable and encouraged.(Pretend you are writing a newspaper headline.)Précis: Include a one sentence précis (35 words or less)summarizing the main outcome/finding of the study.List in this order: All author(s)full names AND ALL DEGREESas desired when published, academic and institutionalaffiliations, sources of support, and other acknowledgements.Restate for publication the corresponding author's name,address, telephone and FAX numbers, with e-mail address.ABSTRACT: :Do not restate the title as the title will alwaysappear with the abstract. On a separate page (2) provide anabstract-summary of about 200 words, clearly and conciselystating in paragraphs titled respectively the Background andPurpose (or Problem), Methods of study, the major Results,and principal Conclusions. CONSERVATIVE statements as toIMPORTANCE, recommendations, and applications may beappropriate. The abstract should be factual, specific andsufficiently complete to provide the reader a quick andcomprehensive view of the content of the paper. [Avoidgeneralizations (i.e. "are discussed") OR "baiting" the reader byholding back or out on your results or conclusions.] TEXT CONTENT: Manuscript material should be organizedinto the following parts in this order: ABSTRACT;

INTRODUCTION (BACKGROUND AND PURPOSE ORPROBLEM); MATERIALS, SUBJECTS AND METHODS;RESULTS*; DISCUSSION OF RESULTS; CONCLUSIONS (&recommendations) REFERENCES; TABLES; LEGENDS FORFIGURES; FIGURES. In the "Discussion of Results", do not introduce new referencematerial. Instead, we expect you to integrate YOUR NEWRESULTS into the current body of knowledge. Specifically: yourresults should be compared to results obtained by prior workers:Confirmations and agreements should be pointed out. Butdiscordances also require enumeration, discussion, andexplanation. Unique or unexpected results demandinterpretation. The statistical significance* of results must beconsidered and their application should also be entertained.

REFERENCES: Order these numerically in sequence as theyappear in the text. Indicate a reference number in the text witha full sized Arabic numeral enclosed in parentheses, i.e. (1). Onthe separate Reference page they should be numberedconsecutively and typed double-spaced. Author's names andJournal titles should be abbreviated, without periods, as in IndexMedicus. For journals punctuate in the following order:Author'(s) last name Initials ["et al" acceptable for more than3]:[colon] Article title with sub-title, if any.[period] IM Journalabbreviation [Bolded] year; volume number in Arabic numerals:inclusive pages. Example:

1. Jones AB, Jones CD, Jones EF, et al: Results ofLaser Surgery for Strabismus. J Outst Surg l999;2:301-304.

For book references: author, title, volume (if more than one)edition number (if other than the first), publisher, city and year.If the reference is a chapter in a book, the order changes asfollows: the author of the chapter, title of the chapter, "in" booktitle, volume, edition, editors, publisher, city, year, inclusivepages of the chapter. Authors are responsible for accuracy.

TABLES: Always "portrait" (< 7" W), NOT "landscape"configuration which requires undesirable sideways position..FIGURES: PHOTOS, GRAPHICS, DRAWINGS Electronic submission, email or on CD is usually acceptable.Standard Hard copy methods: Photo materials for halftones(photographs, photomicrographs, electron micrographs,roentgenograms) should be submitted cropped and unmounted.On the back of each print, affix a pretyped label with the figurenumber, an arrow and/or "top" indicating the top edge, and thelast name of the first author. Line drawings, charts, anddiagrams should be professionally prepared. For computergenerated graphics, please submit originals, rather thanphotographic prints. Typewritten labels and lettering are notacceptable in graphics. Insure that lettering is large enough tobe legible if and when reduced for publication. Legends for Figures: typed double-spaced in consecutiveorder on a separate page following References. Start each withfirst author's name in parentheses. Indicate scale whenappropriate. State clearly the point which the Figure isillustrating. Use arrows on photos liberally to identify and pointout structures. [Assume the reader is not an expert like you arebut rather an ignorant student.]

SOURCES, CREDITS, PERMITSQuotations must be accurate and give full credit to the source.Brief properly credited quotes do not require permission of theoriginal author or publisher ("fair use"). For large amounts of textor any figures previously published permission to quote andreproduce must be obtained by the submitting author: originalcopies of the letters from the original author and publishergranting permission to reproduce the work must accompanyyour manuscript. Photo permits: if the subject can berecognized, i.e., any picture which contains more than just eyesand an unidentifiable bridge of the nose, written permission topublish the picture must be obtained from any subject over age8 years old (and the parents if a minor under age 18) andsubmitted with it.* Statistical Analysis of Results Mandatory. But give "exact"probability values (i.e., p = .06). Do not use relative p values(i.e.,p >< .05). The term "statistically significant", definedtraditionally as a p #.05, is a totally arbitrary and unscientificterm and should not be used (J Lab Clin Med 1988. 111:501).But do consider whether a result may be "clinically/medicallysignificant". rev 22:1()005 PER

Binocular Vision & People and Places, News and Announcements Second Quarter of 2007

Stra bism us Qu arte rly© Volume 22 (No.1): page 11

D. BRIAN STIDHAM MEMORIAL LECTURESHIP

LECTURE to be published annually in Binocular Vision and Strabismus Quarterly

Donations Solicited to Fund LectureshipTo the Editor: The Pediatric Ophthalmology community lost a great doctor last October 6, 2005, with thedeath by murder of D. Brian Stidham. I am attempting to create an endowed lectureship to remember Brian in our communityand within pediatric ophthalmology, and wonder if I could ask you to consider helping in thisregard. I know that your journal concentrates on strabismus and binocular vision, but couldI interest you in publishing the "Stidham Lecture in Pediatric Ophthalmology and Strabismus"that will hopefully be given on a yearly basis? I would work with the presenter to makecertain that a manuscript would be produced that would be of acceptable quality. Having atarget journal for the presentation would be a great carrot to draw top speakers to Tucson ona yearly basis to give such a talk. We have raised $14,000 towards a target of $50,000 endowment that would ensure that thelecture would be perpetuated. I am committed to continue fundraising until the goal is met.If Binocular Vision and Strabismus Quarterly would serve as the publisher of the named lecture,I feel certain we will be able to both attract top speakers and donors to remember Brian in theyears ahead, and to provide a great lectureship in pediatric ophthalmology and strabismus toour professional community which would enjoy greater readership and distribution.

Joseph M. Miller, M.D., MPHHead, Ophthalmology and Vision Science

University of Arizona, Tucson, ArizonaIn reply: We are honored to be asked and will most definitely be pleased to publish this lecture eachyear. We would encourage our readership to donate to this fund: Checks should be madepayable to The University of Arizona Foundation with memo of "Stidham Endowment" and sentto Dr. Miller at U AZ, Ophthalmology, 655 N. Alvernon Way, Ste 108, Tucson AZ 85711. - PER

ADVICE for authors submitting papers to Binocular Vision & Strabismus Quarterly©

1. READ & FOLLOW INSTRUCTIONS FOR AUTHORS! In addition:2. READ & FOLLOW INSTRUCTIONS FOR AUTHORS! In addition:

Reviewing the literature: A proper review of the literature starts with areview of current and appropriate textbooks, especially the latest edition(currently the Sixth of von Noorden’s Binocular Vision and Ocular Motilityby Mosby, and Duane’s loose-leaf text Clinical Ophthalmology.Anticipating a future requirement, it will only be to your credit now tospecifically state what was included in your literature search, i.e., thetopics or subjects and the sites searched. For any article submitted herethat should include at a minimum, Index Medicus (Medline) from 1966 tothe present, Index Bnoculus Primus, 1985 to the present, and theInternet for the American Orthoptic Journal.

Aceptable TERMINOLOGY not acceptableAHP Abnormal Head Posture face turn head turn chin up/down head up/down Head tiltretroequatorial myopexy Fadenoperationretroequatorial myopexy posterior fixation

suturesuspension-recession hang back, hang

looseBielschowsky Head Tilt Test three step teststrabolog-y, ist Strabismolog’y, istexact p values “ S t at is t ic al ly

significant”

Re: “lost to followup” - Avoid this at all costs; First it raises the possibilitythat the patient had a (=) bad result or was otherwise so unhappy withtheir care that they never came back - or went elsewhere or wentnowhere out of fear or dissatiscation. If they are “lost followup” you just

cannot refute the possiblity that one those very unhapy thingsppened!Second it is inexcusable - medico-legally. Third: It reflects poorly on youas both a health care professional and as a scientist and Fourth: underthe worse of circumstances suggests or indicates that you maydiscriminate against those of lower socio-economic status (researchfindings).

WRITING STYLE IS IMPORTANT TOO:(from Investor’s Business Daily Nov. 26, 1997 by Morey Stettner)“Make Dry Data Come Alive in Your Reports ... tips on making yourtechnical writing come alive:1. Remember that less is more. ... simplify your language and pruneextra words. Eliminate jargon, and keep your sentences and paragraphsshort. ‘If you write in little bites, you break down lots of information for thereaders so that it’s easier to absorb,’ said Carolyn Mulford, president ofThe Writing Coach. ...2. White in the active voice. ... For example, write ‘When you review thedata, you will note these trends’. Avoid saying ‘These trends were notedupon a review of the data.’ Another example: Write ‘We will examine’, not,‘This has been examined’. ...3. Insert ‘talking subheads’. ... unbroken text can intimidate any reader,... organize your writing in sections with each carrying an easy tounderstand subhead ... a talking subhead ... alerts the reader of whatyou’re about to discuss ... for instance, instead of heading a section with‘Cost of Scanners’ try ‘Rising Cost of the Next Generation of Scanners’.... subheads should average 7 workds.4. Run a test. ... ask someone in your audience group to read it.

TABLES: Don’t forget the crowding phenomenon. It works in Tables too.We prefer spaces to lines to separate the items in a Table. You can alsoget more material within whatever size limits you may have, using spacesinstead of lines, especially vertical lines. Horizontal lines are less of a sin.

-PER

2007 Pertinent Meeting CalendarDATE PLACE NAME OF MEETING SPONSOR CONTACT

April 11-15(Wednesday- Sunday)

SeattleWashingtonUSA

AAPOS Amer Assn for Pediatric Ophthalmol and Strabismus

Maria Schweers, COTel: 515-964-7835 FAX: [email protected]

May 6-10(Sunday- Thursday)

Ft LauderdaleFloridaUSA

ARVO The Association for Research in Vision and Ophthalmology

Joanne AngleTel: 240-221-2900 Fax: 240-221-0370www.arvo.org

May 17-19(Thursday- Saturday)

CincinnatiOhioUSA

AACOMidwestRegional

Amer Association Certified Orthoptists

Laurie Hahn-Parrott, CO, COT3333 Burnet Ave. Pav 4-510Cincinnati OH 45229-3039Tel: 513-636-8168 FAX: [email protected]

May 20-23(Sunday- Wednesday)

MykonosGREECE

ESA European Strabismological Association

Aktina-City Congress SA26 Filellinon St.Athens Greece GR 105 58Fax: [email protected]

June 20-23 (Wednesday- Saturday)

MontrealQuebecCANADA

CanadianOrthoptic Society

Canadian Orthoptic Society

[email protected] Quan, TCOS [email protected]

July 13-15 (Friday- Sunday)

PhiladelphiaPennsylvaniaUSA

AACOEasternRegional

Amer Association Certified Orthoptists

Alexandra Brock, [email protected]

November 10 (Saturday)

New OrleansLousianaUSA

Pre AAO3rd PediatricOphthalmology Day

Wright FoundationAlcon Laboratories

Gabby: [email protected]: [email protected]

November 10-13(Saturday- Tuesday)

New OrleansLouisianaUSA

AAO/AACO American Academy of Ophthalmology &American Association Certified Orthoptists

AAO: FAX: [email protected]: Ron Biernacki, [email protected]

Future AAPOS Meetings: 2008 Washington, D.C. April 2-6, 2008

Future AAO/AACO Meetings: 2008 Atlanta, Georgia November 8-11, 20082009 San Francisco, California October 24-27, 20092010 Chicago, Illinois October 16-19, 20102011 Orlando, Florida November 5-8, 2011

Future ARVO Meetings: 2008 Fort Lauderdale, Florida April 27-May 2, 20082009 Fort Lauderdale, Florida May 3-7, 2009

World Ophthalmology Congress

The name World Ophthalmology Congress was approved last year and will replace the former and traditional "International Congress ofOphthalmology". Therefore the 2006 World Ophthalmology Congress corresponds to the 30th edition of the ICO.

Future Meeting Dates: 2008 - China, Hong-Kong June 28-July 2, 2008 www.woc2008hongkong.org2010 - Berlin, Germany June 6-10, 2010 www.woc2010.de2012 - Chicago, USA, November 10-13. 2012 (combined meeting with AAO)

XI International Orthoptic Congress

The XI International Orthoptic Congress will be held in Antwerp, Belgium, in May 2008. Startmaking plans now to attend.

Gill Roper-Hall has been selected to give the Burian Lecture. For more information, visit: www.ioacongress2008.org

Binocular Vision & People and Places, News and Announcements First Quarter of 2007

Stra bism us Qu arte rly© Vo lum e 22 (No .1):

An eye medical scientif ic e-periodical page 14

MEETING REPORT !!!

The Proceedings of the Ocular Motor Tonus Symposium in 2006sponsored by Smith-Kettlewell EyeResearch Institute can be accessed onthe Smith-Kettlewell website:https://www.ski.org.

William Anninger, M.D. Appointed

The Children's Hospital of Philadel-phia is pleased to announce the appointmentof William Anninger, MD, as attendingphysician, Division of Ophthalmology. Dr.Anninger has been educated at the Universityof Michigan, Dartmouth Medical School,interning at Cambridge City Hospital ofHarvard University, completing his oph-thalmology residency at the William HavenerEye Institute, at Ohio State University. Hecompleted his pediatric ophthalmology fel-lowship at the Children's Hospital inPhiladelphia. He can be reached at the maincampus at 215-590-2791.

RESEARCH OPPORTUNITIES

Research Funds Available The Blind Childrens Center (BCC) isagain pleased to announce the availability offunding to support research to gain betterunderstanding of visual impairment inchildren from birth to 5 years of age. Oneyear grants of up to $15,000 will be awarded.For questions and application forms, contactMidge Horton, Executive Director, BlindChildrens Center, 4120 Marathon St, LosAngeles CA 90029. Tel: 323-664-2153 ext.326.

The Contact Lens Association of Oph-thalmologists has announced the availabilityof 3 grants, of up to $10,000 each, to beawarded to provide support for researchspecifically concerned with issues directlyrelated to contact lens science and/or ocularanterior segment science. Grant applicationsmay be obtained by visiting the CLAO HomePage at www.clao.org or by calling the officeat 877-501-3937.

Study RecruitmentPhotorefractive Keratectomy (PRK) forAmetropia in Children Evelyn A. Paysse, MD of the BaylorCollege of Medicine, Texas Children'sHospital, and colleagues are recruiting

patients to participate in a funded study forchildren with bilateral ametropic amblyopiawho have been non-compliant withtraditional treatment. The study involvesusing PRK to fully or partially neutralize therefractive error and thereafter following thechildren for a one year period. They willalso be collaborating with the developmentalpediatric physicians to determine if changesin visual outcome affected the developmentof children with amblyopia. If you havechildren in your practice between the ages of2-7 years old with a bilateral high myopicametropia of at least 7 D, bilateral highhyperopic ametropia of at least 4 D, orbilateral high astigmatic ametropia of at last3.5 D, who are non-compliant with tradi-tional treatment options, please considerenrolling them in this study. Contact Dr.Paysse at 832-822-3237 or her research co-ordinator, Maria Castanes at 832-822-3257.

Practice Opportunities

Fresno, California: Large MD/OD practice.State of the art facility and satellite office.Affiliated with Children's Hospital ofCentral California. $10,000 signing bonus,bonus plan, benefit and relocation package.Fax resume to the human resourcedepartment at 559-256-8504 or contact ScottBridgman, CEO at 559-256-8500. Visit theirwebsite at eyeqvc.com

Albuquerque, New Mexico: Children's EyeCare of New Mexico. Two hospital affil-liations. Major contributor/participant forPEDIG studies. A division of GoldblumFamily Eye Care Center. Contact: ToddGoldblum, MD, 303 Mulberry NE, Suite D,Albuquerque NM 87106. Fax: 505-842-0650. email: [email protected]

Public Safety Hazards

from Academy Express February 8, 2007. IsA Complete Ban of Cell Phones inOphthalmology Departments Necessary?British researchers placed cell phones incontact with 23 electronic ophthalmicdevices, as well as at distance of 3 m, 1 mand 30 cm away. No device showed anyinterruption or cessation of function.

Binocular Vision & Here We Go, Charg ing Fu ll Thro tt le and Head long In to the In te rne t. BV&SQ First Quarter of 2007Stra bism us Qu arte rly© Stops the Presses! All But Totally, and Re-Establishes Its Old Website at Vo lum e 22 (No .1):A n eye medical scienti fic e-periodical BINOCULA RVISION.NET for Continuing E-Publication of this Now E-Periodical Pages 15-16

Page 15

EDITORIAL: Here We Go, Charging Full Throttle and Headlong into the Internet.Binocular Vision and Strabismus Quarterly Stops the Presses! All But Totally, and Re-establishes Its Old Website atBINOCULARVISION.NET for Continuing E-Publication of this Now E-Periodical

It has been a monstrous amount ofwork over the past four or five months, abouta thousand hours of my time, primarilybecause we have had to finally give up ouraddiction to old WordPerfect 5.0 wordprocessing and learn Gates’(biggest crook inworld history) Hated Word since WP 5.0 isnot convertible to Word. In fact, WP 5.0 isn’treally convertible directly even to Word-Perfect 10 or anything beyond Word-Perfect5.5. WordPerfect 10.0 will at least accept andpartially convert our 5.0 files to 10. And WP10 does still have its original great ”RevealCodes” feature which is vastly superior to theminimal code information provided by Bill inHated Word.

Since yours truly does most of thelayout work, it was he who had to learn allthis new stuff. It has taken me reading,working, help-begging, and the infinite trialand error trial and error at the keyboard thatis so unavoidable, somewhere about twentyweeks of 50-60 hours work each to learnenough about Hated Word and WordPerfect10, to process and finish the manuscripts forthis first issue of our twenty-second year.

BV&SQ will be available for all sub-scribers at Binocularvision.net by the timeyou read this. In fact, you may have alreadybeen notified by e-mail with a link directly tothat website, and may have already read thisissue. We have tried to maintain the tradi-

tional appearance of the old yellow printedBV&SQ with which you are all familiar.

We have adopted a somewhat largertype font because there is some unpredictableloss of resolution when you put the typesetpages through the process of becoming pdf’s(“portable document files or format”) whichis de rigeur for the internet so that everybodycan read them (with the help of the freeAdobe reader software, of course). But wehave no idea exactly what equipment eachsubscriber has to view each issue onthe web,so for starters, better too big than too small.

As a subscriber, there is nothing morefor you to do than going to the website,signing in and viewing the pages of eachissue. The subscription rates are unchanged.If you also paid extra for airmail, that will berefunded to you. Instead of receiving a hardcopy of BV&SQ by post, you will get an emailnotifying you that the next issue is availableon our website and the email will contain ahot link to the website, so that all you willhave to do when you get there is sign in, thenselect whatever parts of that issue you want toread and/or download and make hard copiesat no fee. There will be no time limits on youruse of any material on the website. We willarchive, on the website, all issues from nowon and as a subscriber you will havepermanent 24/7/52 access to all issues fromhere on. And in the future we plan to also

Binocular Vision & Here We Go, Charg ing Fu ll Thro tt le and Head long In to the In te rne t. BV&SQ First Quarter of 2007Stra bism us Qu arte rly© Stops the Presses! All But Totally, and Re-Establishes Its Old Website at Vo lum e 22 (No .1):A n eye medical scienti fic e-periodical BINOCULA RVISION.NET for Continuing E-Publication of this Now E-Periodical Pages 15-16

Page 16

archive on the website all previous 84 issuessince 1985.

Now for those who need or want, inaddition, an old fashioned hard copy of theissues, we hope to “hand-make” some ofthese because we would like to provide allcontributors with at least one “original” hardcopy from which they can make original-likecopies for their fans, chairman, bosses, andpromotion committees. But since we will notbe printing hundreds of copies using theprinting press, such copies will be expensive,for us,and for you. We are estimating about$47 per issue hard copy (which is coin-cidentally for now the same that it will costnon- subscribers to purchase on the websitejust the right to read and download a wholeissue for one week. Therefore, nonsubscriberswill have to pay $188 per year to viewBV&SQ one issue at a time for a week a time.As a subscriber, you are paying a maximumof only $84 per year (and as little as $64 ayear for 3 year subscribers) for the sameright. In addition to paying $104 to $124 lessper year, you will have permanent anytimeaccess to every issue.

In This Issue

This is sort of an amblyopia issue inthat the two major original scientific researcharticles are on amblyopia, and similarlyconsider aspects of the final results of ourconventional current treatment.

Johnson DA. Relative scotomata in the“normal” eye of functionally amblyopicpatients. A Scanning Laser Ophthalmo-scope (SLO) microperimetric study.Binocul Vis Strabismus Q 2007; 22:17-48

This is huge and outstanding piece ofwork and Dr. Dr. (I do love that continentaldoubling way of recognizing PhD’s) Johnsonsent us an abridged version of his originalAOS paper. One might have expected hisremarkable discovery if you were as familiarwith the amblyopia literature as he is. And heshares that knowledge with us in theextensive review of the amblyopia literature

within his Discussion. It is a superb review.Unilateral amblyopia is a disease of a bilat-erally represented part of the brain and so istruly always really a bilateral disease!

Garoufalis P, Georgievski Z, Koklanis K.Long-term vision outcomes of conventionaltreatment of strabismic and anisometropicfunctional amblyopia. Binocul Vis Strabis-mus Q 2007; 22:49-56

These orthoptist researchers were asdismayed as the rest of us when pennypinchers in Britain tried to destroy ourintentions to find and treat amblyopia inchildren (see their reference 1) asunworthwhile. But they did something aboutit. They did some research which well refutesthose obsessive-compulsive “evidence-basedmedicine” Brits. They were ready to destroyour efforts as medical professionals, doctors,and orthoptists and technicians totally justbecause there were insufficient perfect ran-domized controlled outcome studies. They arereally NUTS! And that goes for all you“authorities”, editors and such out there whoshare that obsession. That’s not rationalscience or medicine.

Farzavandi S. Strabology report of[Wright’s] 2nd pediatric ophthalmologyand strabismus day; “An extravaganza inLas Vegas, USA”. Binocul Vis Strabismus Q2007; 22:57-63.

We must commend Dr. Ken Wright forhis enthusiastic creation of these manystrabology /pediatric ophthalmology meet-ings. They do recreate a happier time formost of us, a time when there were fewer ofus to attend our meetings, and it was easier tocontact older original friends from trainingtimes, always somehow reassuring. A three-peat is scheduled for the 2007 NOLA AAO

Both because of the length of Dr. Dr.Johnson’s major and important thesis, and tosimplify creation of our first e-issue, there isno section on abstracts, no Hyde Park Editor’ssoapbox-blog. But rest assured, the secondissue this year will see those features restored.And you will see it soon -PER.

Binocular Vision & Re lative S coto m ata in th e "N orm al" E ye of Fu nction ally Am blyopic Pa tients First Quarter of 2007Stra bism us Qu arte rly© A Scanning Laser Ophthalmoscope (SLO) Microperimetric Study Vo lum e 22 (No .1):A medical scientif ic e-periodical D. A. Johnson, MD, PhD Pages 17-48

Page 17

ABSTRACT: Purpose: To evaluate amblyopic patients with scanning laserophthalmoscope (SLO) microperimetry to determine whether SLO assessmentand data might provide useful information in our understanding of amblyopiaand determine its utility in the evaluation of amblyopic patients. Methods: In this retrospective, selected for SLO testing case series, clinicaldata of forty-six patients with amblyopia were reviewed after completion oftreatment for anisometropic or strabismic amblyopia. Ten ophthalmologicallyage-matched normal patients served as controls. All patients were tested withthe SLO, specifically evaluating for the presence of macular scotomata. SLOfindings were assessed within each group and between groups. Results: A macular scotoma was found in the amblyopic eye of 25 of 26anisometropic amblyopic patients and all 20 strabismic amblyopia patients.Twenty of the 26 patients with anisometropic amblyopia also had a relativescotoma in the non-amblyopic “normal” contralateral eye. All 20 patients withstrabismic amblyopia also had a non-amblyopic “normal” contralateral eyescotoma. None of the normal control patients had a scotoma in either eye.Several ocular and binocular clinical features were correlated to these scotomafindings within and between groups. Conclusion: The SLO proved useful for the assessment of some features ofamblyopia. A scotoma was identified not only in the amblyopic eye of all butone amblyopic patient, as expected, but also in almost all of the fellow non-amblyopic, presumed "normal" contralateral eyes, and in spite of treat-mentnormalization of visual acuity and stereoacuity in several cases. Thus, theocular and binocular pathological effects of unilateral functional ambly-opiaare not limited to the amblyopic eye but may also be seen, to a subclinicaldegree, by SLO microperimetry in the supposedly normal contralateral eye aswell as in the apparently successfully treated previously amblyopic eye.

65 Original Scientific Article

Relative Scotomata in the "Normal" Eye ofFunctionally Amblyopic Patients. A Scanning Laser Ophthalmoscope (SLO)Microperimetric Study

DAVID A. JOHNSON, M.D., Ph.D.from Eye Associates of Wilmington, Wilmington, North Carolina

Received for consideration October 27,2006; accepted for publication November 9, 2006.This work is an abridgement of a thesis submitted, and accepted, in partial fulfillment of

requirements for membership to the American Ophthalmological Society, May 2006.The author has no financial interest in any product mentioned in this study.

Acknowledgements: The author would like to thank Dr. Bruce Kater for technical assistance with the SLOand Steven Lewallen for assistance with computer measurements of the scotoma area.----Correspondence/compl.reprint requests to: Eye Associates of Wilmington, 1729 New Hanover MedicalPark Dr. Wilmington NC 28403. Fax: 910-763-4608. email: [email protected]

Binocular Vision & Re lative S coto m ata in th e "N orm al" E ye of Fu nction ally Am blyopic Pa tients First Quarter of 2007Stra bism us Qu arte rly© A Scanning Laser Ophthalmoscope (SLO) Microperimetric Study Vo lum e 22 (No .1):A medical scientif ic e-periodical D. A. Johnson, MD, PhD Pages 17-48

Page 18

INTRODUCTION

Amblyopia is a common cause ofvisual loss, despite increasing under-standing of its causes and mechanisms. Itis defined (1) as a "unilateral or bilateraldecrease of visual acuity caused by formvision deprivation and/or abnormal bin-ocular interaction for which no organiccauses can be detected by the physicalexamination of the eye and which,... is re-versible by therap[y]". Amblyopia is esti-mated to affect 1-4% of children (2,3) andapproximately 2.9% of adults (4). Its path-ophysiology stems from early abnormalbinocular interactions (usually from stra-bismus) or form vision deprivation in oneeye (from uncorrected anisometropia) or,less commonly, both eyes (uncorrectedhigh hyperopia). Not infrequently, multiplefactors are involved in the same patient.

Numerous approaches have beenemployed in the clinical and researchstudy of amblyopia. Visual acuity meas-urement in the clinical setting usually isby age-appropriate subjective testing,methods such as Snellen charts, Allencards, Tumbling E game, etc. Pre-verbalchildren require forced choice preferentiallooking tests (Teller cards), determinationof fixation preference when strabismic, orinduced tropia testing when eyes aregrossly aligned. Evaluation may includemeasurement of contrast sensitivity andsubjective tests of binocular cooperation,such as Worth 4 Dot Test and stereo-acuity. More recently, research methodshave employed newer techniques, such asfunctional magnetic resonance imaging(fMRI) (5) or positron emission tomogra-phy (PET scanning) (6) in the investigationof the cortical neuro-physiologic mecha-nisms underlying amblyopia. Histologicalevaluation of visual neuronal pathways invisually deprived animals and humanshas been studied as well (7-11).

The advent of the scanning laserophthalmoscope (SLO) has brought ano-ther tool into the armamentarium of theeye clinician. The SLO has been used toadvance the evaluation of the optic discsin glaucoma, by providing greatly enlarg-ed, quantitative, three-dimensional imag-ing and analysis of the disc surface (12,13). Other advantages of the SLO include

micro-perimetry, where it has been usedto enhance evaluation of point of fixationand fixation stability in conditions such asmacular dystrophies (14), idiopathic mac-ular holes (15), age-related macular de-generation (16,17), and pre- and postop-erative visual function after retinal sur-gery (18). Another area in which the SLOhas been particularly valuable is in lowvision rehabilitation, where micro-perim-etry aids not only in the localization of apatient's preferred retinal locus of fixation,but also as a device to assist rehabilita-tion of low vision patients in fixationstability and vision optimization (19-21).

The purpose of this study was touse the SLO as a microperimetry device toassess macular stimulation threshold,and the presence and patterns of sco-tomata in the eyes of post-treatmentamblyopic and normal control patients.Further analysis was used to find dis-tinctions between different etiologies ofamblyopia and to seek identifiable charac-teristics of patients that correlate withtheir clinical response, or lack thereof.

SUBJECTS and METHODS

Patients:Forty-six patients with previously

treated amblyopia were selected from theirprior treatment records and studied bySLO exam. Patients included those withstrabismic or anisometropic amblyopia.Ten ophthalmologically normal patientsserved as controls. Human studies com-mittee and institutional review boardapproval was obtained and informedconsent granted by each subject'sparents. HIPAA regulations were enforced.

Amblyopia was defined as meetingone of these three criterions: 1. in pre-verbal children, a strong fixationpreference for one eye over the other ifstrabismic or by induced tropia testing(vertical prism) if child was orthotropic. 2. an interocular visual acuity differenceof $2 lines using projected pictures in age-appropriate children on a B-VAT visionmeasuring instrument (Mentor O & O,Norwell MA) at 20 feet testing distance; or 3. an interocular difference of $2 logMARlines at distance visual acuity testing withthe B-VAT, using either Snellen letters or

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HOTV letters with surround bars at a 20foot (6M) testing distance.

Children who were pre-verbal at theonset of treatment were included in thisstudy only if followup was sufficiently longthat a final visual acuity could be deter-mined by criteria number 3 above.

To divide the amblyopic patientsinto two manageable groups for compari-son and analysis, strabismic amblyopiawas defined as that occurring in strabis-mus of at least ten prism diopters,withoutanisometropia. If a strabismus was lessthan ten prism diopters and there wasclinically significant anisometropia, thesepatients were placed in the group ofanisometropic amblyopia. Most of thesepatients were in fact orthotropic. Clinicallysignificant anisometropia was defined asan interocular spherical refractive errordifference of 1.0 diopter or greater or anastigmatic difference of 1.50 diopters orgreater. For purposes of data reporting,the refractive error difference between eyeswas regularly expressed as the sphericalequivalent.

Details of prior treatment of ambly-opia: in all cases, a patient was not diag-nosed as having amblyopia, nor wastreatment started, unless the defineddifference in interocular visual acuitypersisted after at least 4 weeks of spec-tacle correction of refractive errors, whenappropriate. Need for spectacles was basedupon cycloplegic retinoscopy and, whenage-appropriate, a cycloplegic refraction.

All patients included in the studyalso needed to be free of confoundingcoexisting ocular and binocular disordersthat might be responsible for decreasedvisual acuity or coexisting medicalproblems that might limit reliability ofvisual acuity measurements and anytesting measures.

The normal control patients selec-ted, in the same age range as theamblyopic patients, were required todemonstrate 20/20 best corrected visualacuity in each eye, normal binocularalignment, 40 seconds of arc stereoacuityand normal ocular movements andanatomy.

Amblyopia was treated conven-tionally either by occlusion (by adhesivepatching) or atropine (1% eye drops)penalization of the normal contralateraleye. Atropine penalization was institutedonly in patients whose visual acuity inthe amblyopic eye was 20/100 or better.

Some patients began amblyopiatreatment while still pre-verbal and,therefore, in them, initial acuity wasassessed by fixation preference if stra-bismic, or if not, by induced tropiatesting, if orthotropic. However, interimand final visual acuity was measured inall patients at 20 feet (6 M) using age-appropriate testing, including projectedpictures, HOTV optotypes (with surroundbars) or Snellen letters. All stimuli werepresented on a calibrated B-VAT. AllSnellen visual acuities were converted toLogMAR format for proper statisticalanalysis (22).

Patients were excluded if they hadundergone amblyopia therapy prior toinitial evaluation by the author. Patientswere included only after having com-pleted a course of amblyopia therapy bythe author and were felt to have reachedeither (1) equal visual acuity in the twoeyes or (2) a less than equal but improvedand stable acuity in the amblyopic eyewhich had remained stable after ambly-opia treatment had been discontinued forat least 3 months

Because performance of the SLOtesting involves considerable coopera-tion, patients were excluded from thestudy if they could not cooperate andfollow instructions while maintainingsteady fixation on a target at the slit lampbiomicroscope, which simulates thesubject-patient cooperation necessary toperform the SLO measurements.

Ophthalmologic measurements ob-tained included visual acuity, binocularalignment, stereopsis at near using theTitmus stereoacuity test, the 4 diopterbase-out prism test, Worth 4 Dot test, slitlamp examination, dilated funduscopicexamination and cycloplegic refraction.Amblyopia data obtained included bestcorrected visual acuity in both eyes atbeginning of treatment and end of

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treatment, age at onset of treatment,method of amblyopia treatment, treat-ment duration, need for re-treatment, ageat SLO testing and all follow-up time fromthe onset of treatment to last follow-up.

Microperimetry:Microperimetry was performed with

a scanning laser ophthalmoscope (Rod-enstock Instruments GmbH, Model 101,Ottobrun-Riemerling, Germany). This SLOis a Class 1 Laser appliance and complieswith laser protection regulations DIN- VDE0837 and IEC 825. This lowest laserclassification is achieved because the laserbeam is always constantly scanning theretina and never remains static on thesame spot. Safety shutdown security is inplace for failure of the scanning mech-anism or limits on the duration of exami-nation.

SLO microperimetry is similar toconventional perimetry in that it is apsychophysical test. That is, a stimulus ispresented at a point remote from fixationand the patient is to respond if thestimulus is appreciated or recognized.Except for the normal control patients, allstudy subject-patients tested had clin-ically-defined amblyopia. All test pointswere applied in the macular region. Thetesting strategy is described below. Thescanning laser ophthalmoscopic micro-perimetry was performed by a low visionspecialist who was masked to patientdiagnosis.

Definitions:The microperimetric stimulus Thres-

hold was defined as the least intensestimulus which elicited a reliable rec-ognition response. The threshold for agiven eye may or may not be in the fovealarea. During testing, threshold wasdefined as the stimulus level at which thepatient recognized approximately 50% ofthe presented stimuli. Testing was begunat a level determined empirically to be thatrecognized by most patients. Thatintensity was reduced until the patientcould no longer recognize a stimulus andthen the stimulus intensity was increaseduntil approximately 50% of deliveredstimuli were recognized. The location ofgreatest sensitivity and the threshold levelin any given eye may be quite different in

any individual eye from that point in thefellow eye. This point may be centered onthe fovea. The point of greatest retinalsensitivity in an eye with a relativescotoma may be more distant from thefovea than the most sensitive point in thefellow presumed normal eye. It followsthat the entire macular area of an eyemay have a higher threshold than that ofthe fellow eye and within itself contain anabsolute or relative scotoma.

An absolute scotoma was definedas a group of contiguous points in themacular area where the brightest ofstimuli failed to elicit a recognitionresponse. This corresponded to stimuli at0 dB which was the brightest stimulusdeliverable.

A relative scotoma was defined astested points in a definable contiguousarea in the macula where a brighter stim-ulus was required to elicit recognitionthan the intensity required for recognitionin areas bordering it on all sides. That is,points outside the scotomatous area moredistal to the fovea were more sensitive(required a less bright stimulus) thanwere points closer to the fovea.

Relative scotomata differ in "den-sity"; i.e., the level of stimulus intensity(dB) required for recognition. In mostpatients with a relative scotoma, thesensitivity to recognition was uniformthroughout the scotomatous region and asecond relative scotoma was notidentified. However, there were patientswho demonstrated both an absolutescotoma and a surrounding relativescotoma. In those few patients, thescotoma area was considered to be thatencompassed by the relative scotomaincluding the absolute scotoma.

Testing:In SLO microperimetry, the retina

is viewed at all times during the testingby way of an infrared laser (780 nm), at abackground intensity of 10 candela/m2

which is barely perceptible by the pa-tient.

The examiner monitors the pa-tient's macula as a gray-scale image inreal time on a computer monitor. (see Figure 1, next page, below, or right).

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Figure 1 (Johnson DA): Scanning laser ophthalmoscope testing. In a dimly lit room, thepatient's chin and forehead are positioned to allow the subject to view the SLO screen(left). The examiner views the macula, in real time, to monitor fixation, deliver stimuliand map scotomata on a computer monitor (right).

First, the patient is instructed tofixate on an illuminated cross 1.0 degreein size presented in the center of the field.The fixation cross is also visible asprojected on the retina to the examiner onthe computer monitor. Per the instruction,it is assumed that the localization of thefixation cross represents the patient'spreferred retinal locus of normal fixation.The examiner can also visualize whetherthis locus coincides with the anatomicfoveal area as it should.

Now, a reference point on the retina(for example, the intersection of twoprominent blood vessels) is chosen and setto allow compensation for unintended orundesired patient eye movements. Iffixation locus slips or changes, accuratecentration of the macular image can be

maintained and the eccentric stimulustest point accurately registered (23).Thus, the examiner can assess, by directand continuous real-time observation, thepatient's stability and locus of central orbest fixation. As a result, a stimulus wasnot presented unless the patient wasfixating properly. Hence, the concept of"fixation loss", as is used as a measure ofreliability in automated perimetry, doesnot apply in SLO microperimetry in thatNO stimuli were presented if the patientwas not properly centrally or maximallyfixating.

The stimulus was presenteddirectly on the retina by a Helium-Neon(HeNe) laser (545 nm). A stimulus with adiameter of 10 minutes of arc (=50 umdiameter) was used. The stimulus could

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Figure 2 see next page (Johnson DA): SLO images of a control patient. The patientwas instructed to fixate on an illuminated central cross. A reference marker (red cross)was marked at a prominent vessel crossing to allow all test points to be recorded inprecise register on the image. After determining threshold sensitivity, the macula wasscanned for scotomatous area. Scanning of the right eye (top) was started at 19 dB(yellow). When no scotoma was identified more peripherally, stimulus intensity waslowered to determine threshold and testing for scotomatous areas repeated. Basedupon the threshold determined for the right eye, scanning of the left eye (bottom) wasstarted at lower stimulus intensity (dark green). Stimulus intensity is greater at lowernumerical values (red) and lessens in intensity as numerical values increase (brown,yellow, green, blue). Each colored bar represents a 5 dB range but stimuli could bechanged in 1.0 dB steps.

be regulated and graded in intensity andwas presented for 100 ms, thus gen-erating a static, rather than kinetic,perimetry assessment. The instrument'sstimulus intensity range is from abrightest possible intensity of 0 dB to thedimmest stimulus of 40 dB (a rangeequivalent relatively to 10 to the 40th

power) and is adjustable in steps of 1 dB(10X difference for each dB; a 2 dBdifference =100X). Patients were allowed2.0 seconds to respond to each stimulus.When the stimulus was recognized, thepatient pressed a toggle switch to registertheir perception.

When a positive response was made,or 2.0 seconds had transpired, the retinalimage was frozen and the stimulus datapoint was registered on the macular imagein the precise location where it wasdelivered. The previously designated ana-tomical reference point then allowed eachstimulus to be marked on the overlay inits exact location relative to other stimuli.

On the SLO images, the perimetrystimuli presented are shown on the retinalimage in true relative size and are color-coded for relative intensity. Stimuli arealso, in addition, icon shape-coded torepresent whether the stimulus wasdetected or not detected mapping thescotoma. Filled circles represent posi-tively-recognized test points, open trianglea missed (unrecognized) test point.

Initial testing was begun with a 19dB stimulus, which was an intensityempirically determined to be detectable bymost subjects. The right eye was always

tested first. The stimulus was firstpresented in close proximity to thefixation cross. Several points in this areawere tested to determine whether thepatient responded positively or failed torespond. If the patient failed to respond,the test area was expanded centrifugallyto determine if there was any maculararea in which the stimulus was detected.That is, testing addressed whether thepatient responded to a 19 dB stimulus ina macular area more distal from thecentral macula (or fovea). If no areas ofgreater sensitivity were identified, thestimulus intensity was increased and theabove strategy repeated.

If positive responses were noted inan area not at the point of fixation, thestimulus intensity was reduced to de-termine threshold at that location (seedefinition above). This, point then,represented a scotoma border. Numerouspoints were then tested in and out of thispresumed scotoma, to define its bordersand size. This process was continueduntil the scotoma could be mapped andoutlined as accurately as possible, muchlike scotoma mapping is performed withGoldmann kinetic perimetry.

If a definable scotomatous regioncould be so identified, the stimulusintensity was increased within thescotoma borders until recognition, todetermine the "depth" of the scotoma.That is, the intensity of a stimulusnecessary to evoke a response within thescotoma was determined. This stimulusintensity was then used to "re-map" thescotoma borders. Although uncommon, it

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was possible that a relative scotoma ofgreater "depth" might lie within a relativescotoma of lesser "depth" or an absolutescotoma might lie within a relativescotoma.

If there was a positive response to a19 dB stimulus centrally, several pointswere tested more distally to determine ifthis level of sensitivity was uniformthroughout the macula. Then stimulusintensity was decreased and the lo-calization method described above wasrepeated. Such testing, as the stimulusintensity was reduced, might reveal arelative scotoma, but one requiring alesser intense stimulus to discover andmap than those that might be uncoveredwith the original 19 dB stimulus. This wasdone until the subject failed to recognizeany stimuli presented. The stimulusintensity was then gradually increaseduntil an approximately 50% positiveresponse rate was reached. This was thendetermined to be the subject's threshold,as defined above. This method was used toexamine each quadrant unless scotomamapping had already encompassed eachquadrant.

Using the above strategy, the num-ber of points necessary to thoroughly testa patient varied widely among patients,depending on the presence or absence of ascotoma, its borders and depth. Forexample, a subject in which a scotomawas not found could be tested forthreshold and the macula scanned forsensitivity in a much shorter time than apatient with a complex scotoma shape andsize. Measurements in each patienttypically took 5-10 minutes per eye

Retesting of missed points wasperformed to determine reliability. Ifretesting confirmed the initial finding, theexamination continued. If not, furthertesting at that point was performed foraccuracy in terms of scotoma size andstimulus intensity required for re-cognition. Because the test points areapplied while viewing a real-time image ofthe macula, precision of retest points wasvery high.

However, such a high magnificationview demonstrated that "steady" fixation

does not mean "motionless" fixation whenviewed at the microscopic level. Usinganatomical landmarks, reapplication of astimulus was typically very precise andwithin the range of no more than one-halfstimulus width (one half of the standardstimulus diameter.)

The mapping of scotomata thres-holds, size and depth, could be done withstimulus variations of 1.0 dB. However,the final SLO instrument printout onlypresents color-coded data points over aspan of 5.0 dB; two "same" color pointson the printout could be up to 5.0 dBdifferent in intensity. Hence, scotomaboundaries were mapped and recorded asto stimulus intensity as the SLO wasbeing performed, and not strictly fromprinted data, so as to allow as accurate amapping as possible (see legend, to Figure2 on prior pages)

The retinal images, with scotomatamapped, were digitally scanned andconverted to bit-map form. The area wasmeasured using AutoDesk ArchitecturalDesktop 3.3 software (Autodesk, Inc., SanRafael, CA). Data were expressed as arc-min2 based on a projected calibrationimage from the SLO.

Statistical Methods: Data is presented as mean ± standarddeviation. Data analysis was performedusing Minitab Release 14 statisticalsoftware (Minitab, Inc, State College, PA).Comparisons between eyes of individualpatients and comparisons in the same eyepre- and post-treatment were made usingthe paired t-test. Comparisons betweengroups were analyzed with the twosample t-test. Correlations betweenvariables were assessed with the Pearsoncorrelation coefficient test.

Statistical interpretations of thesestatistical test results were based on theconventional traditional definition of"statistical significance" being equal to aprobability value (for the probability ofrejecting the null hypothesis) equal orless than 0.05 (indicating the probabilityof the result not being due only to chanceof less than 0.05 or one in 20), an entirelyempirical value. If this probability is lessthan 0.05 or 20;1, say for example only

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0.06 or about 17:1, then that comparisonof different items is said to be NOT"statistically significant" and is then, byconvention and tradition, discarded asbeing NOT different from chance alone -rather, it could be due to chance aloneand is therefore considered not due tosome real-world factor or cause (beinginvestigated). Statistical Significance sodefined is here-after indicated by quota-tion marks as in "Statistical Significance"or "Statistically Significant(ly)"

RESULTS

Demographics:A total of 56 patients were included

in this study (Table 1). Ten were normalcontrol patients, 46 were "experimental"subjects. These 46 patients comprised twogroups, based upon diagnosis of ambly-opia etiology type: anisometropic ambly-opia (n=26) and strabismic amblyopia(n=20) (see Table 1, below). Twenty-five

were male; thirty-one were female. Agesat time of SLO testing ranged from 66 to146 months with a mean of 104.1 ±20.2months.

Normal Control Subjects:Ten patients (7 male, 3 female)

served as normal control patients whounderwent SLO testing (Table 1). Each ofthese subject-patients had normal:bilateral best corrected visual acuity,binocular alignment, binocularity, ster-eopsis, and normal anatomy. None hadany prior ophthalmologic interventionother than spectacle wear for physiologicmyopia in three patients. All were healthywith no confounding medical problemsthat might affect performance of theclinical or SLO examination.

The mean age of the normal controlgroup at time of SLO testing was 110.0±25.1 months, which was not"statistically significantly" different from

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the 26 anisometropic amblyopia patientstested (p=0.51, two sample t-test) or the20 strabismic amblyopia patients (p= 0.35,two sample t-test).

Using the SLO, threshold was de-termined and the central macular areastudied for scotomatous regions. Thres-hold sensitivity at the SLO was 26.0 ±3.9dB, with a range of 18-31 dB. No sco-tomatous areas were found in either eye ofany of the 10 control patients. The SLOimages of a normal control patient areseen in Figure 2.

Anisometropic Amblyopia Patients Twenty-six patients (9 male, 17 female)with anisometropic amblyopia were treat-ed for amblyopia and tested with the SLO(see prior Table I). Of these 26, fully 20were in fact orthotropic. The remaining 6had small angle strabismic deviations, allunder 10 prism diopters but also clinicallysignificant anisometropia.The mean age atwhich amblyopia was diagnosed andtreatment begun was 66.5 ±22.2 months,with a range of 24.0-113.0 months.Followup averaged 47.8 ±26.4 months(range 8-98 months). Mean age at SLOtesting was 104.0 ±19.1 months with arange of 66-142 months. The right eye wasthe amblyopic eye in 10 patients and theleft eye was in 16 patients. The meandifference in the refractive error betweenthe amblyopic eye and the fellow eye,expressed as sphericalequivalent, was 2.68±1.76 diopters.

The mean visualacuity at the start oftreatment in the ambly-opic eye was LogMAR0.65 ±0.27 (approximateSnellen equivalent,20/90, (see Table II,next page) and, in thefellow, non-amblyopiceye, was LogMAR 0.10±0.12 (Snellen equiv-alent, 20/25). The meanacuity in the amblyopiceye after treatment wasLogMAR 0.30 ±0.23(Snellen equivalent,20/40), reflecting animprovement of 3.51

±2.29 logMAR lines, on average (range 0.9lines; p=0.000, paired t-test, see Table II).Acuity in the non-amblyopic eye post-treatment was LogMAR 0.02 ±0.04(Snellen equivalent, 20/21), with achange of 0.84 ±1.35 lines from pre-treatment (range 0.0-4.77 lines). This wasalso a "statistically significant" improve-ment (p= 0.002, paired t-test), althoughthe average improvement in visual acuitywas less than one LogMAR line.

The mean pre-treatment acuitydifference between the amblyopic eye andthe fellow eye was 5.53 ±2.41 LogMARlines (range 2.0-11.0 lines) whichimproved to a mean post-treatmentinterocular visual acuity difference of2.86 ±2.26 lines (range 0.0-9.0 lines, seeTable II). This improvement/change/difference is "statistically significantly"different (p=.000, paired t-test), reflectingan average improvement of interocularvisual acuity difference of 2.71 ±2.06LogMAR lines.

Eighteen of these 26 patients hadmeasurable stereopsis. Six of thesepatients had a stereoacuity of 50 secondsof arc or better.

Threshold sensitivity averaged 17.8±3.9 dB (range 9-24 dB) in the amblyopiceye and 22.5 ±2.8 dB (range 17-27 dB) inthe non-amblyopic eye of these aniso-metropic patients (see Table II, andFigure 3, below). (Recall that a lower

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Figure 3, prior page (Johnson DA): Boxplots of SLO threshold sensitivity in non-amblyopic (left) and amblyopic (right) eyes of patients with anisometropic amblyopia.The shaded box represents the middle 50% of observations with the horizontal line in theshaded area indicating the median data value. The lines extending vertically from thebox extend to indicate the range: lowest and highest values among the data.

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Figure 6 (Johnson DA): Boxplot of the SLO scotomaareas of the non-amblyopic (left) and amblyopic(right) eyes of anisometropic patients. The shadedbox represents the middle 50% of observations withthe line in the shaded area indicating the median datavalue. The lines extending from the box indicate therange: lowest and highest values of the data.

Figure 4, next page: (Johnson DA): SLO images of a patient with anisometropic amblyopia. Testing was started in the normal right eye (top) with a 19 dB stimulus (yellow). Once threshold

was obtained (see Methods), the macula was tested for presence of a scotoma. If a scotoma wasidentified, its borders were determined. Missed points (open triangles) surrounded by recognized points(filled circles) localized scotoma borders.

In the amblyopic left eye (bottom), a larger scotoma was identified and mapped at a brighterstimulus intensity than that needed in the right eye. Stimulus intensity could be varied in 1.0 dB steps buta single color code encompassed a 5.0 dB range. Hence, two points of the same color on the final print-out could vary up to 5.0 dB. Scotoma borders are delimited as the test progresses. This patient had 20/20visual acuity in the right, non-amblyopic eye before and after treatment. The left, amblyopic eye had apre-treatment visual acuity of 20/60 and improved, with treatment to 20/20. This patient demonstrated40 seconds of arc stereoacuity after treatment.

value corresponds to a light stimulus ofgreater intensity.) Threshold for the non-amblyopic eye was "statistically signif-icantly" different from the normal controlpatients (p=0.002, two sample t-test).Threshold sensitivity in the amblyopic eyeswas "very" ( specifically defined as p=0.001or less) "statistically significantly" differ-ent from the matched non-amblyopic eye(p=0.000, paired t-test) and from normalcontrol threshold levels (p=.000, twosample t-test). However, a correlationbetween the threshold in the amblyopic eyeand that in the non-amblyopic eyedid not reach a "statisticallysignificant" level (p=0.94, Pearsoncorrelation). That is, eyes withreduced sensitivity in theamblyopic eye did not all have acommensurately reduced sensi-tivity in the non-amblyopic eye,with a probability better than0.05.

In 25 of 26 anisometrop-ically amblyopic patients, ascotoma was measured in theamblyopic eye. The mean scotomaarea was 162.5 ±178.7 arc-min2

with a range of 0.0-512.5 arc-min2

(see prior Table II). Twenty of these 26 aniso-

metropically amblyopic patientshad a relative scotoma in thefellow, non-amblyopic eye. Theother 6 patients did not show ascotoma in the fellow eye. Themean scotoma size, including thesix patients not showing ascotoma, was 42.2 ±46.2 arc-min2

(range 0-150.2 arc-min2). Averagescotoma size, excluding the sixpatients who did not have ascotoma, was 54.8 ±45.5 arc-min2

(range 4.95-150.2 arc-min2). The SLOimages of two patients with anisometropicambly-opia with scotomata areasdelineated are shown in Figures 4 & 5.on the following two pages.

In this group, the area of thescotoma in the anisometropically ambly-opic eye was, on average, 3.9 times largerthan the scotoma, if any, in the fellow eye(p=.001, paired t-test, see Figure 6,below). Of only those patients with a

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Figure 5, prior page (Johnson DA): SLO images of a patient with anisometropicamblyopia. The non-amblyopic right eye (top) had a pre-treatment visual acuity of 20/30which, by treatment end for the contralateral amblyopic eye, had spontaneouly improvedto 20/20. The amblyopic left eye (bottom) visual acuity improved from 20/60 to 20/20 withtreatment. This patient demonstrated 40 seconds of arc stereopsis at the end of treatment.

scotoma in the fellow eye (20/26), thescotoma in the amblyopic eye was, onaverage, 3.7 times larger than the scotomain the fellow eye (p=.002). This includes fivepatients where the scotoma in the normalfellow eye measured LARGER than that inthe amblyopic eye, but was mapped at alower stimulus intensity than thatnecessary to evoke a response in theamblyopic eye (i.e., the stimulus to elicit aresponse in the presumed normal felloweye was much dimmer than that necessaryin the amblyopic eye). There was a correla-tion between the scotoma size in the am-blyopic eye and that in its fellow eye(p=.048, Pearson correlation, just mar-ginally "statistically significant"). That is,patients with larger sized scotomata in theamblyopic eye had, on average, a largersized scotoma in the fellow eye.

One patient did not have an ident-ifiable scotoma in either the amblyopic orthe non-amblyopic fellow eye. There wereno distinct clinical features of this patientthat differed patently from the group as awhole. Visual acuity was 20/20 in thenormal non-amblyopic eye and in theamblyopic eye visual acuity improved from20/40 to 20/20.with treatment. Stereo-acuity was 50 seconds of arc (i.e., "nor-mal") at the end of treatment.

Data was therefore analyzed todetermine if any features of the SLOscotoma findings correlated with ambly-opia patient clinical treatment outcomes.There was a correlation between ambly-opic eye scotoma area and the interocularvisual acuity difference before treatment(p=.034) and also after treatment (p=.000,Pearson correlation). This correlation alsoexisted in the non-amblyopic eye before(p=.048) and after treatment (p=.003,Pearson correlation). That is, scotomataareas in the amblyopic and non-amblyopiceyes were larger in patients with greaterinterocular visual acuity differences before

treatment and after treatment.

There were "statistically significant"correlations between the scotoma size inthe presumed normal non-amblyopic eyeand the visual acuity of the amblyopiceye. Scotoma size in the presumednormal non-amblyopic eye was larger inthose patients whose amblyopic eyevisual acuity was poorer both beforetreatment (p=.035) and after treatment(p=.003, Pearson correlation).

As a group, patients with largeramblyopic eye scotomata had a poorerLogMAR amblyopic eye visual acuity atthe start (p=.034) and at the end ofamblyopia treatment (p=.001, Pearsoncorrelation). Such a correlation did notexist in the normal non-amblyopic eyewhere scotoma size was not "statisticallysignificantly" correlated with pre-treat-ment (p=.490) or post-treatment visualacuity (p=.285) of the amblyopic eye.

To further evaluate whether SLOfindings correlated with amblyopic clin-ical features, two subgroups of patientswere assessed. One subgroup comprisedthe 7 patients who had the best finalvisual acuity in the amblyopic eye and theother subgroup comprised the 7 patientswho showed the poorest final amblyopiceye visual acuity. (Seven patients werechosen because 5 patients had the "thirdpoorest" final visual acuity in theamblyopic eye.)

In the two subgroups of patientswith anisometropic amblyopia, those whoshowed the poorest final visual acuity inthe amblyopic eye (LogMAR 0.57 ±0.17lines, n=7; Snellen equivalent 20/74) had"statistically significantly" larger macularscotomata in both the amblyopic andnon-amblyopic eye than those found inthe patients whose amblyopic eye finalvisual acuity was among the best (0.03

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±0.05, n=7; Snellen equivalent 20/21).Scotoma areas in the amblyopic eyemeasured 325.0 ±192.4 arc-min2 in thepoorer outcome patients versus 60.0 ±67.1arc-min2 in the better outcome patients(p=.011). Similarly, scotoma area in thenon-amblyopic eye of the poorer outcomepatients (68.2 ±57.8 arc-min2) was greaterthan that measured in the normal non-amblyopic eye of patients with betteroutcomes (12.56 ±11.86arc-min2, p=.047).

No such relationship existed be-tween SLO thresholds and clinical out-comes in the two "experimental" sub-groups. Threshold in the amblyopic eye ofthe better outcome patients (17.4 ±2.8 dB)was not "statistically significantly" differ-ent from that found in patients with pooreramblyopic eye final visual acuity (17.0 ±5.5dB, p=.859). Threshold was also not"statistically significantly" different betweenthe presumed normal non-amblyopic eye ofthe better outcome group (22.0 ±1.8 dB)versus the poorer outcome patients (23.6±3.0 dB, p=.266).

Data was similarly analyzed for thesubgroups of amblyopic patients whoshowed the greatest number of lines ofvisual acuity improvement in the amblyopiceye (6.85 ±1.42 LogMAR lines, n=5) versusthe subgroup with the fewest lines ofimprovements (0.16 ±0.29 LogMAR lines,n=5). There did not appear to be anyfeatures of the SLO data that correlatedwith visual acuity outcome in terms ofnumber of LogMAR lines improved.Between these two subgroups, there wasno "statistically significant" difference inthreshold in the amblyopic eye (p=.952) ornon-amblyopic eye (p=.363). Nor was thereany "statistically significant" differencebetween amblyopic patients who improvedthe greatest or fewest number of lines ofvisual acuity in terms of the scotoma size ofthe amblyopic eye (p=.847) or presumednormal non-amblyopic eye (p=.754).

As a group, scotoma area in theamblyopic or non-amblyopic eye was notcorrelated with level of stereoacuity.Patients who had high (i.e., normal) levelsof stereopsis (a stereoacuity of 50 secondsof arc or better) were compared to thosewho showed no measurable stereopsis. Sixpatients had excellent stereopsis (a

stereoacuity in 5 of them of 40 seconds ofarc; the sixth, of 50 seconds of arc). Eightanisometropic patients had no meas-urable stereopsis. Scotomata in both theamblyopic and non-amblyopic eyes werelarger in these 8 who had no stereopsis.The scotoma area in those with goodstereopsis averaged only 37.4 ±33.4 arc-min2 in the amblyopic eye and 10.9 ±12.1arc-min2 in the presumed normal non-amblyopic eye whereas the scotoma areasin the amblyopic and non-amblyopic eyesof patients with no stereopsis were muchbigger in area, averaging 209 ±207 arc-min2 (p=.055) and 58.2 ±60.5 arc-min2

(p=.68), respectively. Remarkably, thishuge difference was only marginally(p=0.055) "statistically significantly" dif-ferent due to the large standard dev-iations noted.

Patient age was not a factor in thisstudy in terms of either response toamblyopia treatment or performance onSLO testing. There was no correlationbetween age and pre- or post-treatmentvisual acuity, number of LogMAR linesimproved or interocular visual acuitydifference. This was true of both theamblyopic and the non-amblyopic eye.Similarly, there was no correlationbetween age and SLO results (thresholdor scotoma area) in either the amblyopicor the non-amblyopic eye.

In summary, for these anisome-tropic amblyopia patients, there was:- 1. an inverse correlation between the sizeof the amblyopic eye scotoma and thequality of amblyopic eye visual acuityboth prior to initiation of amblyopiatreatment and at the end of treatment. 2. a positive correlation between scotomasize and number of lines differencebetween the amblyopic eye and thepresumed normal fellow eye both at thestart and end of treatment. Patients withlarger amblyopic eye scotomata areas hadcommensurately larger scotomata in thefellow, non-amblyopic eye. Those patientswhose amblyopic eye had better finalvisual acuities had smaller macularscotomata in both the amblyopic andpresumed normal non-amblyopic eyesthan did those patients whose finalamblyopic eye visual acuity was poorer.

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Figure 7 (Johnson DA): Boxplot of SLO threshold sensitivity in non-amblyopic (left) and amblyopic (right) eyes of patients with strabismicamblyopia. The shaded box represents the middle 50% of observationswith the horizontal line in the shaded area indicating the median datavalue. The lines extending vertically from the box extend to indicate therange: lowest and highest values of the data.

Strabismic Amblyopia PatientsTwenty (9 male, 11 female) were

treated clinically and evaluated with theSLO (see Table I, prior pages ). The meanage of amblyopia diagnosis and treatmentwas 62.7 ±29.6 months (range 15.0-129.0months). Followup averaged 49.4 ±25.1months (range 12.0-91.0 months). Meanage at SLO testing was 101.3 ±19.3 months(range 71.0-142.0 months). The right eyewas the amblyopic eye in 8 patients; theleft eye in 12 patients.

Seven of these 20 patients had anaccommodative esotropia type of stra-bismus, which was well controlled withspectacle correction and surgery wasunnecessary. The other 13 of these 20patients had either a non-accommodativedeviation or a mixed accommodative andnon-accommodative deviation for whichsurgery had been performed. In this lattergroup, only 1 patient was exotropic. Theothers were all esotropic. The preoperativedeviation averaged 31.1 ±9.5 prism diopters(range 20.0-45.0 prism diopters). Allpatients in this group had a deviation of 10prism diopters or less on alternate prismcover testing at final followup.

For this group, the pre-treatment visual acuity in theamblyopic eye was LogMAR 0.48±0.15 (Snellen equivalentapproximately 20/60) with arange of LogMAR 0.18 - 0.70 (seeTable II) and pre-treatment felloweye visual acuity was LogMAR0.10 ±0.08 (Snellen equivalentapproximately 20/25), with arange of 0.0-0.3 LogMAR. Aftertreatment, the visual acuity in theamblyopic eye had improved, onaverage, 2.35 ±1.8 LogMAR lines(range 0.00-6.00 lines; p=.000),yielding a post-treatment visualacuity of LogMAR 0.25 ±0.13(range 0.10-0.48; approximatemean Snellen equivalent 20/36;see also Table II). Normalfellow eye acuity post-treatment was LogMAR 0.06±0.05 (range 0.0-0.1; Snellenequivalent 20/23), reflecting achange of 0.50 ±0.70 LogMARlines (range 0.0-2.0 LogMARlines; p= .009).

There was a "statistically signifi-cant" difference between the interoculardifference in visual acuity before and aftertreatment. Prior to amblyopia therapy,the mean interocular difference was 3.81±1.47 LogMAR lines. After therapy, thisdifference was 1.97 ±1.23 LogMAR lines(p=.000, paired t-test), reflecting anaverage improvement of interocular visualacuity difference of 1.85 ±1.74 lines(range 0.0-6 lines; Table II).

Stereopsis was measurable in 10patients, but all but two were poorer than100" of arc. One achieved a normal 40" ofarc stereopsis after strabismus surgery.The other had 100 secs of arc stereopsis.

Threshold sensitivity averaged 17.3±5.8 dB (range 0-24 dB) in the amblyopiceye and 21.6 ±3.3 dB (range 15-27 dB) inthe non-amblyopic eye (Table II). Thresh-old sensitivity was reduced compared tocontrol patients in both the amblyopic eye(p=.000, two sample t-test) and the non-amblyopic eye (p=.000, two sample t test).There was a "statistically significant" dif-ference in threshold sensitivities betweenthe amblyopic and non-amblyopic eyes ofthe same patient (p=.008, paired t-test,see Figure 7,below). Also there was a

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Figure 8 (Johnson DA): Strabismic amblyopia: Scatterplot of the amblyopic eye and non-amblyopic eye thresholds. A best fit regression line is shown (p=.022, Pearson correlation).

Figure 10 (Johnson DA): Boxplot of the SLO scotoma areas of the normal non-amblyopic eye(left) and amblyopic (right) eyes of strabismic amblyopia subject-patients. The shaded boxrepresents the middle 50% of observations with the horizontal line in the shaded areaindicating the median data value. The lines extending vertically from the box extend toindicate the range: the lowest and highest values of the data.

"statistically significant"correlation between thetwo eyes, in that a lowerthreshold level in theamblyopic eye correlatedwith a lower thresholdlevel in the non-amblyopiceye (p=.022, Pearson cor-relation; see Figure 8,above).

In all 20 patients, ascotoma was found in theamblyopic eye, averaging157.4 ±171.6 arc-min2

with a range of 23.3-699.6arc-min2 (Table II). All 20strabismic patients were

also found to have ascotoma in the felloweye, averaging 70.3±77.0 arc-min2 (range9.75-274.9 arc-min2).The SLO images of apatient with strabis-mic amblyopia areshown in Figure 9,next page.

For this group,the area of the sco-toma in the amblyopiceye was 2.23 timeslarger than that in thefellow eye (p=.038,paired t-test; see Fig-ure 10, below). How-ever, in 3 patients, thescotoma in the normalfellow eye was actually

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Figure 9 (Johnson DA): SLO images of a patient with strabismic amblyopia. After determiningthreshold, scotomata were delineated in the right, non-amblyopic eye (top) and left, amblyopiceye (bottom). This patient's visual acuity in the non-amblyopic eye was 20/25. The amblyopiceye visual acuity was 20/60 and did not improve with conventional amblyopia treatment. Thepatient demonstrated no stereopsis before or after amblyopia treatment.

Binocular Vision & Re lative S coto m ata in th e "N orm al" E ye of Fu nction ally Am blyopic Pa tients First Quarter of 2007Stra bism us Qu arte rly© A Scanning Laser Ophthalmoscope (SLO) Microperimetric Study Vo lum e 22 (No .1):A medical scientif ic e-periodical D. A. Johnson, MD, PhD Pages 17-48

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larger than that in the amblyopic eye. But,ineach case, the amblyopic eye required agreater stimulus intensity to evoke aresponse than did the normal eye. Therewas not a correlation in this group betweenscotoma size in the amblyopic and non-amblyopic eyes (p= .426, Pearson correla-tion).

Although there was not a "statis-tically significant" correlation between thevisual acuity in each amblyopic eye at thestart of amblyopia treatment and the acuityin that eye after treatment (p=.535, Pearsoncorrelation), there was a correlation be-tween the visual acuity of the amblyopic eyebefore treatment and the number of lines ofacuity improved by therapy (p=.003, Pear-son correlation). This is not surprising inthat it might be expected that those eyeswith poorer initial visual acuity will show agreater improvement, in terms of lines ofacuity improved, than those eyes with betterpre-treatment acuity. Also, there was acorrelation between the difference in thenumber of LogMAR lines between theamblyopic and fellow eyes and the numberof LogMAR lines improvement in theamblyopic eye with treatment (p=.006,Pearson correlation). That is, the greater thepre-treatment interocular acuity difference,the greater the improvement in LogMARlines of visual acuity.

In the amblyopic eye, threshold leveland scotoma size were not linearly related(p=.720, Pearson correlation). However,there was a correlation between thresholdsensitivity and scotoma area in the non-amblyopic eye. Patients who required amore intense stimulus for thresholddetection were found to have larger sco-toma areas (p=.008).

Analysis was done to determine if SLOfindings correlated with the clinical findingsof patients with strabismic amblyopia. Therewas a “statistically significant”correlationbetween the size of the amblyopic eyescotoma and the LogMAR line differencebetween the eyes at the start of treatment(p=.002, Pearson correlation) but not aftertreatment (p=.129, Pearson correlation).There were no correlations between scotomaarea in the non-amblyopic eye and anyvisual acuity features of the amblyopic eye,including amblyopic eye pre-treatmentvisual acuity (p=.809), post-treatment visualacuity (p=.660) or lines of acuity improved

(p=.915, Pearson correlation).

The subgroup of the 5 patients withthe best final visual acuity in the amblyopiceye (LogMAR 0.10 ±0.0, Snellen equivalent20/25) was compared to the 5 patientswhose amblyopic eye showed the poorestfinal visual acuity (LogMAR 0.41 ±0.07,Snellen equivalent 20/51). There was no"statistically sig-nificant" difference betweenthe groups in threshold sensitivity of theamblyopic eye (p=.50, 2 sample t-test) or thenon-amblyopic eye (p=.085, 2 sample t-test).

There was a greater difference inthreshold sensitivity between the ambly-opicand non-amblyopic eyes of patients withpoorer final amblyopic eye acuity (p=.004,paired t-test) as opposed to that differencein patients with better final acuity (p=.178,paired t-test). That is, patients whose finalvisual acuity in the amblyopic eye waspoorest after treatment had a greaterdifference in threshold sensitivity betweenthe amblyopic and non-amblyopic eyes. Nofeatures of SLO scotoma size were found tocorrelate with final visual acuity outcome ineither the amblyopic or non-amblyopic eyefor either the best or worst final acuitysubgroup. Nor were any of these SLOfindings correlated with stereopsis.

When the patients were subdividedinto those 5 patients whose amblyopicvisual acuity increased the greatest numberof lines (4.84 ±1.08 LogMAR lines) and thosewho had the fewest number of linesimprovement (0.4 ±0.55 LogMAR lines), nocorrelations were found among SLO results.

Otherwise, there were no "statisti-cally significant" correlations between thescotoma size in either the amblyopic eye orthe fellow eye, in each of the following:amblyopic eye acuity at start or end oftreatment, fellow eye acuity at start or endof treatment, treatment duration, number ofLogMAR lines improved with treatment,difference in acuity between the eyes at theend of treatment, age at which treatmentwas begun or ended or age at which theSLO was performed.

Patient age did not appear to be animportant factor in the response to ambly-opia treatment. There was no correlationbetween age and pre- and post-treatmentvisual acuity, number of LogMAR lines

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acuity improved or interocular visual acuity.Age also did not appear to be a factor inSLO performance. No correlation was foundbetween patient age and threshold in theamblyopic (p=.532) or non-amblyopic (p=.088) eye. Nor was age correlated to scotomaarea in the amblyopic (p=.291) or non-amblyopic (p=.605) eyes.

Comparison of Anisometropic to Strabismic Amblyopia Groups

The findings of those patients withanisometropic amblyopia were comparedand contrasted to those of strabismicamblyopia patients. Although the aniso-metropic patients were, on average, slightlyolder than the strabismic patients whendiagnosis was made and treatment begun(66.5 months and 62.7 months, respec-tively), there were no "statistically sig-nificant" differences between the two groupsin terms of age at start of treatment (p=.63,two sample t-test) or age at which treatmentended (p=.72, two sample t-test, Table II).The strabismic group had a longer averagefollowup than the anisometropic group (49.4months and 47.8 months, respectively), butthis also was not "statistically significantly"different (p=.84, two sample test). Treatmentduration was not "statistically significantly"different between the two groups (p=.98).Nor was there a "statistically significant"difference between the two groups in termsof age at which the SLO was performed(p=.64, two sample test).

More patients in the anisometropicgroup had some degree of stereopsis (69.2%)than in the strabismic group (50%).However, only three strabismic patientsreached a stereoacuity of 100 seconds of arcor better, while 6 of the anisometropicpatients achieved 50 seconds of arc orbetter, 5 achieving a normal 40 seconds ofarc.

There was no "statistically signifi-cant" difference between the groups interms of the non-amblyopic eye visualacuity at the start of treatment (p=.95) andnumber of lines improved in the non-amblyopic eye (p=.28, two sample t-test).However, because the anisometropic groupshowed slightly greater improve-ment fromtreatment start to final followup, thedifference between the groups reached"statistical significance" in terms of finalvisual acuity in the non-amblyopic eye(p=.006). Two qualifi-cations are important.

First, the actual clinical difference in finalvisual acuities is quite small (anisometropic,LogMAR 0.015; strabismic, LogMAR 0.055;Snellen equivalents, 20/21 vs. 20/23 re-spectively). Second, in some patients, theinitial pretreatment acuity was recordedusing a projected pictures test. Not onlymight this acuity testing method be lessprecise than letter recognition, thesepatients were considerably younger at theentry point. Thus, the apparent "statis-tically significant" difference most likely haslittle or no clinical relevance or im-portance.

In terms of the visual acuity in theamblyopic eye, there was a "statisticallysignificant" difference between the twogroups at the start of treatment (p=.009),but not at final followup (p=.314, twosample t-test), although the mean acuity ofthe amblyopic eyes in the aniso-metropicgroup was poorer than the strabismic groupat each time point in the study.

There was a "statistically significant"difference between the two groups in termsof the number of LogMAR lines differencebetween the amblyopic and fellow eyes atthe start of treatment (p=.005), and also atthe end of followup (p=.095), with theanisometropic patients having a greaterpretreatment LogMAR line visual acuitydifference between the eyes (5.53 ±2.41logMAR lines vs. 3.81 ±1.47 LogMAR lines,respectively). On average, the amblyopiceyes in the anisometropia group showed agreater LogMAR line improvement thanthose in the strabismic group (3.51 lines vs.2.35 lines, p=.06, two sample t-test).

Thus, although patients with aniso-metropic amblyopia had a poorer visualacuity level in the amblyopic eye pre-treatment and a greater interocular visualacuity difference between the amblyopic andthe non-amblyopic eye, these eyes showed asignificantly greater improvement withtreatment such that amblyopic eye visualacuities of an-isometropic and strabismicpatients were not "statistically significantly"different post-treatment.

There was no "statistically signifi-cant" difference between the two groups forSLO threshold in the amblyopic eye (p=0.74)or the fellow, non-amblyopic eye (p=0.31). Itis of note that in both aniso-metropic andstrabismic amblyopia pa-tients, threshold

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stimulus intensity for recognition in boththe amblyopic and non-amblyopic eyes wasat greater light intensities than in thenormal control patients.

There was no "statistically signifi-cant" difference between mean scotoma areain the non-amblyopic eye in aniso-metropicpatients compared to strabismic patients(42.2 vs. 70.3 arc-min2, p=0.16, two samplet-test), although the normal fellow eyescotoma in strabismic patients tended to belarger. Nor was there a "statistically sig-nificant" difference between amblyopic eyescotoma areas in anisometropic patients(mean 162.5 arc-min2) versus strabismicpatients (mean 157.4 arc-min2; p=.92).There was a "statistically significant" dif-ference between the two groups in terms ofscotoma size related to stereopsis. Whenanisometropic patients were sub-dividedbased on stereopsis, those patients withbetter stereopsis had smaller macularscotomata in both the amblyopic and non-amblyopic eye than did those with nostereopsis. No such correlation existedamong strabismic ambly-opia patients.

In summary, among all featuresanalyzed, the two experimental groups were"statistically significantly" different in onlyseveral areas: stereopsis (better in theanisometropic group), visual acuity in theamblyopic eye pre-treatment (poorer in theanisometropic group), post-treatment visu-al acuity in the non-amblyopic eye, andLogMAR lines different at start (greaterdifference in the anisometropic group) butnot at final followup.

END of RESULTS SECTION

SUMMARY-DISCUSSION

In this study, a selected collection of46 patients that had been treated foranisometropic or strabismic amblyopia wasevaluated with the Scanning Laser Ophthal-moscope after reaching optimal visual acui-ty in the amblyopic eye. Forty-five of the 46patients who were tested with the SLOshowed a macular scotoma in the amblyopiceye. Forty of the 46 were also found to havea relative scotoma in the contralateralfellow, presumed "normal" eye. In contrast,no scotoma was identified in either eye ofany of the 10 normal control patients.

Scanning Laser Ophthalmoscopy (SLO)Developed in the late 1970s-1980s,

SLO has shown increased clinical utility inthe last 10-15 years. Its use has beenshown to be of benefit in optic nerveanalysis (12,13), retinal assessment ofmacular lesions (14,15), assessment ofretinal foci that underlie metamorphopsia(16-18), and microperimetry (19-21), as wasits use in this study.

The SLO uses a weak laser beam toscan the retina, generating a raster (scan-ning) image of the retina that can be viewedon a monitor. Simultaneously, a secondHeNe laser (545 nM) can project a stimulusof variable size, intensity and durationdirectly onto the retina. It is directed by theexaminer, guided by a real-time view of theretina, including reference points set tocontrol for eye or patient movement (23).Pupillary dilatation is not required formacular viewing on the SLO.

As a microperimetry tool, the SLO hasbeen most extensively used in low visionevaluation of patients with macular lesions,especially age-related macular degeneration(19-21). Affected patients may develop fovealscotomata, resulting in the development ofan extra-foveal preferred retinal locus (PRL)of fixation. The SLO allows the examiner todeter-mine that portion of the retina thepatient is using for fixation. If it is foundthat another retinal area provides greatersensitivity, the patient may be "trained" tore-fixate with this more sensitive retinallocus.

In this study, the SLO was used toassess for the presence, size and depth ofscotomata in patients with amblyopia ofvarious types and contrast these findingswith a control group. This data, along withdata acquired by typical ophthalmologicexamination assessment, was assessedoverall and within groups based onamblyopia etiology, to evaluate whether anyfactors were associated with either am-blyopia type or treatment outcome.

SLO Evaluation of AmblyopiaAmblyopia was defined using gen-

erally accepted current criteria; that is, inpreverbal children, a strong fixation pref-rence for one eye over the other, or, inverbal children, the demonstration, usingage-appropriate testing metgods, a two line

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or greater visual acuity difference betweenthe eyes. Patients were therapeuticallyaddressed utilizing standard conventionalcurrent treatment modalities, includingocclusion and/or atropine penalization. Eyemuscle surgery was performed in thosepatients with a non-accommodative stra-bismic deviation. Appropriate spectaclecorrection was instituted in patients withanisometropia or accommodative esotropia.

Regarding All Amblyopia Patients:Forty of the 46 patients evaluated

showed an improvement in visual acuity inthe amblyopic eye in response to currentlyconventional amblyopia treatment. In theother 6 patients (13%), the visual acuity didnot change from entry level undertreatment. No amblyopic eyes showed adecrease in visual acuity during thetreatment period.

As might be expected, a scotomatousdefect was found in the amblyopic eye ofalmost all patients. Only one anisoetropicpatient did not have a detectable scotomain the amblyopic eye. While true physi-ologic mechanisms may underlie thevariation in scotoma sizes, several factorsare believed to account for the wide range ofscotoma dimensional values obtained.Primary among these is the fact that this isa psychophysical test being performed inchildren. While our subject-children wereselected based on their perceived ability tomaintain steady fixation at the scanninglaser ophthalmoscope, any such test inchildren is subject to their ability to followinstructions, to focus mentally and con-centrate, and maintain visual fixation onthe target. Overall, the patients were felt tohave performed the SLO very well. Mappingof the scotoma on the SLO also lacks someprecision similar to that of Goldmannkinetic perimetry, in that this is a "best-fit"approach based upon patient response andthe SLO operator-examiner's interactivemapping of responses

However, compared to other similarpsychophysical tests, SLO microperimetry isextremely precise in terms of stimulusdelivery location and centration of data onthe final image. This accrues from themacula being viewed in real time whiletesting, so that a stimulus is not deliveredunless the patient is seen to be fixatingproperly in real time. Thus, there is no

measure of perimetric "fixation loss" be-cause a stimulus is not delivered if visualfixation is not central.

This study’s major new finding isthat a heretofore, completely unkown andeven unhypothesized, relative scotoma wasdiscovered to be present in the fellow andpresumed totally "normal" contralateral eyeof 40 of 46 (87% of) treated functionallyamblyopic patients.

In the group as a whole, the scotomasize was, on average, more than 2.5 timesgreater in area in the amblyopic eye than inthe normal fellow eye. In 8 of these patientsthe normal fellow eye scotoma measured alarger area than that in the amblyopic eye.However, in these eight cases and in allcases, the threshold for the testing stimulusin the amblyopic eye was higher, i.e., ofgreater intensity than that required in thefellow normal eye. While this confounds thedata somewhat, it was necessary to increasethe stimulus threshold intensity for ac-curate measurement; this would onlyunderestimate the mean difference betweenthe two eyes.

Anisometropic Amblyopia PatientsAll but 3 of the 26 patients with

anisometropic amblyopia had improvementin visual acuity in the amblyopic eye aftertreatment, averaging an increase of 3.51LogMAR lines improvement. Although theremay have been small variations inamblyopia treatment strategies employedamong this group of patients, the level ofimprovement compares favorably to otherprior studies of amblyopia treatment (24,25). In the 2002 Pediatric Eye DiseaseInvestigator Group (PEDIG) study com-paring atropine penalization to occlusion ofthe normal fellow eye (25), visual acuityimproved 3.16 LogMAR lines in theocclusion group and 2.84 LogMAR lines inthe atropine group. These results arecomparable to the overall improvement of3.51 LogMAR lines in this study. It shouldbe noted that our current study had abroader initial amblyopic eye visual acuityinclusion criteria than the PEDIG studywhich limited inclusion to amblyopic eyevisual acuity to no poorer than 20/100.Fifteen of the 26 anisometropic patients inthis study achieved a final Snellen visualacuity of 20/40 or better in the amblyopiceye; only 5 of the 15, however, (19% of the

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whole group) could read to the Snellen20/20 level. One of these five 20/20patients had no scotoma in either theamblyopic or non-amblyopic eye. Three ofthese five 20/20 patients had no scotoma inthe normal non-amblyopic fellow eye andtheir amblyopic eye scotomata were"statistically significantly" smaller thanthose of the anisometropic group as awhole. These five 20/20 patients wereamong the six anisometropic patients withthe best final stereopsis (40 secs of arc in 5patients, 50 secs of arc in the other).Assessing all other measured clinicalfeatures of these 5 patients failed to revealany "statistically significant" differencesfrom the anisometropic amblyopia group.

While all but one of the 26 patientswith anisometropic amblyopia had a sco-tomatous defect in the amblyopic eye, 20 ofthe 26 were found to have a scotoma in thefellow, presumably normal, eye, despite anaverage normal visual acuity in the non-amblyopic eye of LogMAR 0.015 (Snellenequivalent 20/20.7). This included 3 pa-tients who had stereopsis of 40 seconds ofarc or better.

The amblyopic eye scotoma was, onaverage, almost four times greater in areathan that in the fellow presumed normaleye. There was a direct correlation betweenthe scotoma size of the amblyopic eye andthat of the fellow eye; a larger scotoma inthe amblyopic eye was predictive of a largerscotoma in the normal fellow eye. Sco-tomata areas in the amblyopic and non-amblyopic eyes were also larger in patientswho had greater interocular visual acuitydifferences before and after treatment.Further, anisometropic pa-tients who hadpoorer visual acuity outcomes in theamblyopic eye had larger amblyopic andnon-amblyopic eye scotomata than thosepatients who had better visual acuityoutcomes. There did not appear to be anycorrelation between scotoma size (either inthe amblyopic or fellow eye) and age attreatment start, followup, treatment dur-ation, LogMAR lines of acuity improvementin the amblyopic eye, age at SLO testing orrefractive error difference between theamblyopic and fellow eyes.

Strabismic Amblyopia PatientsAll but 3 of the 20 strabismic

amblyopia patients had improvement in

amblyopic eye visual acuity with treatment,averaging an increase of 2.35 LogMAR lines.The improvement in amblyopic eye acuity inthis study also compares favorably to that ofother amblyopia treatment studies (24,25).Although none of the patients in this groupachieved final amblyopic eye acuity ofSnellen 20/20, 14 of the 20 patients read20/40 or better at final followup.

All of the patients in the strabismicamblyopia group had a measurable sco-toma in the amblyopic eye. A scotoma wasalso measurable in all 20 of the fellow, non-amblyopic eyes. The amblyopic eye scotomawas, on average, more than twice as large inarea as that in the presumed normal felloweye. Unlike that of the anisometropicamblyopia group, there was no linearcorrelation between the size of the scotomain the amblyopic eye and the scotoma in thenormal fellow eye. There was, however, acorrelation between the number of LogMARlines difference between the amblyopic andfellow eyes prior to treatment and the areaof the amblyopic eye scotoma, but not at theend of treatment. That is, the larger thedifference between the amblyopic eye andthe fellow eye prior to treatment, the largerthe size of the amblyopic eye scotoma. Nocorrelation was found between either theamblyopic or fellow eye scotoma size andamblyopic eye acuity at start or end oftreatment, interocular difference in acuity atthe end of treatment, number of LogMARlines improvement in visual acuity, age atentry or age at which the SLO wasperformed, or treatment duration.

Comparison of Anisometropic to Strabis-mic Amblyopia Patients

One question of interest in this studywas whether amblyopia treatment and out-come features or SLO characteristics weredifferent between patients with aniso-metropic amblyopia as opposed to thosewith strabismic amblyopia.

There were no “statistically signifi-cant” demographic differences between thetwo groups. Pre- and post-treatment visualacuities also were not "statistically sig-nificantly" different between the groups, ineither the amblyopic eye or the normalfellow eye.

More anisometropic patients hadmeasurable stereopsis at final followup and

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the quality of stereopsis was superior to thestrabismic patients. Only 3 strabismicpatients had stereopsis that reached 100seconds of arc, while 12/26 anisometropicpatients had stereopsis of 100 seconds ofarc or better. Five anisometropic amblyopiapatients had 40 seconds of arc and betterstereopsis correlated with smaller sco-tomata in the amblyopic and non-amblyopiceyes. This difference may stem from one ofthe fundamental differences in the under-lying cause of the amblyopia. In thosepatients with anisometropia, the image,although degraded in the amblyopic eye,remains in binocular alignment with, andtherefore potentially fusible with, the felloweye, whereas in the strabismic patients, thevisual axes are misaligned and, regardlessof binocular surgical alignment, establish-ment of fusion and stereopsis may bereduced or impossible.

There was a greater pre-treatmentinterocular visual acuity difference in theanisometropic patients than in the stra-bismic patients, and the former group didnot show a "statistically significantly" great-er LogMAR line improvement with treatmentthan the latter group. However, the findingthat the anisometropic patients had betterstereoacuity than the strabismic patientsfurther supports the idea that potentiallyfusible, binocularly aligned eyes, despiterelatively greater degraded image clarity inthe amblyopic eye, have the higher potentialfor superior stereopsis, as was seen in theanisometropic patients.

Threshold levels for stimulus rec-ognition were almost identical in theamblyopic and non-amblyopic eyes of the 2groups. In terms of scotomata sizemeasured in either the amblyopic eye or thefellow eye, there were no "statistically sig-nificantly" differences between the groups.However, the interocular difference betweenamblyopic and fellow eye scotoma size wasgreater in the anisometropic patients thanin the strabismic patients. One mightpostulate that this may stem from a greaterinterocular visual acuity difference in theanisometropic patients and this was, in fact,the case, both prior to treatment and atfinal followup. Thus, although the potentialfor better stereopsis may be greater inpatients with a binocularly fusible, althoughdegraded, image in the poorer seeing eye,the data suggest that such a situation may

not result from, or result in, a smallerinterocular scotoma area difference.

Scotoma Features in the Amblyopic andNon-Amblyopic Eyes

A relative scotoma in an amblyopiceye is not unexpected. Electrophysiologicalexamination of amblyopic patients showsfindings indicative of a scotoma in theamblyopic eye. Fioretto & colleagues (26)evaluated 8 patients with dense amblyopicin one eye using pattern electroretinogram(PERG), pattern visual evoked potential(VEP) and event-related potentials (ERP), inassociation with computerized perimetry, toassess scotoma presence and features.PERG traces from the amblyopic eyes wereirregular in morphology and of reducedamplitude relative to both the non-amblyopic eye and normal control patients.This finding suggests some inherent defectin amblyopic eyes at the level of the retina,specifically, the ganglion cell and amacrinecell layers. However, their study alsoshowed similar response profiles when thenon-amblyopic eye was blurred with filtersto the acuity of the amblyopic eye. Thus,they concluded, if there is a functionaldefect at the level of the retina, it is likelyminor in that simple form degradationproduced similar results.

VEP assessment of the amblyopiceyes found significant reductions in amp-litude and latency relative to the controls.Such a test cannot differentiate a trueconduction pathway deficit (which seemsunlikely) from a more significant deficit atthe level of the lateral geniculate nucleus(LGN), as has been previously demonstratedto be one of the underlying abnormalities inamblyopia. The abnormal ERP findingssuggest a higher level component to thedeficit in amblyopia. Thus, the fundamentaldefect in amblyopia may be multifactorial,but predominantly localizable to abnormalbinocular interactions at the level of thelateral geniculate and ultimately reflected byabnormal binocular interactions at the levelof the visual cortex. As a result, one mightpredict a scotomatous defect on psycho-physical testing. Such was the case in thisstudy, as a scotoma could be mapped in theamblyopic eye of 45 of the 46 patients.

The threshold for stimulus recog-nition was higher in the amblyopic than thenon-amblyopic eye in this study. Similar

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findings were noted by Fioretto & colleagues(26) using automated perimetry. They foundreduced sensitivity particularly in thecentral field. They attributed some of this topoor fixation. It should be noted that thepatients in the Fioretto study, althougholder (aged 11-46 years) had denseramblyopia (approximately 20/100-20/250)than most of the patients in this study.

What was not anticipated on the basisof prior studies and knowledge was thepresence in these amblyopic patients of ascotoma in the fellow, presumably "normal"eye. This was present in 40 of the 46patients in this study. In the 6 patients whodid not demonstrate a normal non-amblyopic eye scotoma, there were noapparent clinical features which dis-tinguished them from other patients in thecohort other than that they had among thebetter stereoacuities and smaller amblyopiceye scotomata of patients tested. However,other patients, who did have non-amblyopiceye scotomata showed similar clinicalcharacteristics.

One might also expect there to besome correlation between amblyopic eyescotoma size and visual function and/orinterocular interactions. For anisometropicpatients, scotoma sizes were larger in theamblyopic eyes with poorer acuity and whenthere was a larger interocular visual acuitydifference. Both of these correlations held atpre-treatment and final followup. Such acorrelation did not exist in the non-amblyopic eye, perhaps because of therelatively small range of pre- and post-treatment visual acuities. In strabismicamblyopia patients, there were no cor-relations, in the amblyopic or non-am-blyopic eye, between scotoma size and pre-or post-treatment visual acuity or numberof lines of improvement. There was a directcorrelation between scotoma areas in theamblyopic and the non-amblyopic eyes ofanisometropic patients but not amongstrabismic amblyopia patients. Stereopsis,as an indicator of interocular interaction,was significantly different between the twogroups with better stereopsis among an-isometropic patients. Further, anisome-tropic patients with better stereopsis hadsmaller amblyopic and non-amblyopic eyescotomata, suggesting that scotoma sizewas smaller when binocular interactionswere greater. Thus, despite form degrad-

ation because of refractive differences, thereare greater interocular relationships inanisometropic patients than in strabismicpatients with image disparity.

VISUAL PATHWAY Features in Amblyopia

The consensus of experimental worklocalizes the defects in amblyopia to thelevel of the lateral geniculate nucleus andits projection to the striate cortex, par-ticularly, layer IV. That is, there is areduction of binocularly driven corticalneurons and neurons driven by theamblyopic eye. Wiesel & Hubel (7), using acat model, and von Noorden & colleagues(9,27), using a primate model, foundshrinkage of the lateral geniculate nucleusthat receives input from the amblyopic eyein experimentally induced amblyopia.Further works of Wiesel, Hubel & Lam (28)and others (29,30) have shown that thevisual pathway representations in thestriate cortex are segregated into columnarclusters of cells in alternating stripes. Eachcolumn is preferentially driven by one or theother eye in an alternating fashion, hencethe term, ocular dominance columns. Theseearly re-searchers found that monocular lidclosure results in shrinkage of the oculardom-inance columns from the affected eye,reflecting loss of geniculo-cortical neuronalconnections.

Such a process is believed to underliethe mechanism of amblyopia, as we know itin humans. Hence, the geniculocorticateprojections from the affected eye fail to"compete" effectively for neuronal con-nections in the striate cortex. As a result,neuronal units that, in normal development,would receive binocular input (and, hence,result in proper visual acuity developmentand binocularity), fail to develop properly,and binocularity is impaired. Such an effectwas found in a human with anisometropicamblyopia by von Noorden, Crawford &Levacy (10).

As is well known clinically and hassubsequently been proven experimentally,reversal of the deficit of the affected eyealone is insufficient to restore good acuityand binocularity. However, penalization ofthe unaffected normal eye, if undertakenduring the so-called "critical period of earlyvisual development" can result inimprovement of visual function in the

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previously affected eye and restore a morenormal anatomical and physiologicalcharacter to the ocular dominance columnorganization (31,32).

Interestingly, damage to one eye afterthe critical period results in loss of corticalmetabolic activity in columns driven by thateye (as would be expected), but no shrink-age in the corresponding ocular dominancecolumn. Horton & co-workers (33) andHendrickson & colleagues (34), using cyto-chrome oxidase (CO) histochemical tech-niques as a marker of patterns of metabolicactivity, found that, in normal monkeys,levels of CO activity are homogeneousthroughout layer IVc in the striate cortex,corresponding to equal ocular input to eachcolumn. However, after removal of one eye,they found a pattern of alternating dark andpale similarly sized columns, representingthe normal and the affected eye.

Subsequently, Horton and Hedley-Whyte (35) noted similar findings in post-mortem examinations of humans. Inpatients with a history of a loss of one eye,even if that loss occurred as much as 20years or more before death, but after thecritical period of early visual development,there was a mosaic of alternating dark andlight CO-labeled columns. In 1993, Horton& Stryker (11) reported another caseevaluating ocular dominance column ap-pearance in humans. A 53 year old male,with documented anisometropic amblyopiafirst diagnosed at approximately 5 years ofage had an amblyopic eye visual acuity of20/400 (refractive difference between theeyes was approximately 6 diopters). Hesubsequently became blind in his non-amblyopic eye from a metastatic lesioncompressing the optic nerve. Post-mortemhistochemical analysis showed that theocular dominance columns of the two eyeswere essentially the same size. Cytochromeoxidase staining (indicative of metabolicactivity) was absent in the columns cor-responding to the previously normal, butsubsequently blinded eye, and present butreduced in width and not occupying the fullwidth of the column in the amblyopic eye.These findings suggest that, once es-tablished, ocular dominance columns maypersist anatomically, if not functionally,even in the absence of retinal input.

Horton, Hocking and Kiorpes (33)

studied a single monkey with naturallyoccurring anisometropia and a behavior-allyassessed visual acuity approximately 20/60in the amblyopic eye. Using autoradio-graphic techniques, there was preservationof clusters of cortical cells arranged incolumns corresponding to each eye.Although these columns were not shrunken,assessment of the same columns forcytochrome oxidase (CO) activity (and,hence, commensurate physiologic activity),revealed a pattern of dark central bands ofpositive stain separated by a pale gap ofcells. Superimposition of the CO imagesonto the autoradiographs showed the darkbands to occupy the center of the oculardominance columns and the paler bands torepresent a transitional zone, which mostlikely represents the electrophysiologicallyless active binocular cell zones.

Kiorpes & associates (36) measuredcortical neuronal responses in monkeys thathad been experimentally rendered eitherstrabismic or anisometropic. In all animals,cortical binocularity was reduced. As hadpreviously been shown by Wiesel &colleagues (28), as well as others (30),columnar clusters of cells were identifiedthat were strongly dominated by one or theother eye. However, they also encounteredtransition zones between the columns whereneuronal units were difficult to drivevisually, suggesting that these cellularregions represent binocular neuronal units,which, in normal monkeys contain the moststrongly driven binocular cells, but, in theirstudy, were absent.

While binocularly driven units werealmost absent in the strabismic monkeys,the authors also found significantly fewbinocularly driven cortical neurons in theanisometropic animals. Quantitatively, therewas not a “statistically significant” differ-ence in proportion of binocularly drivenneuronal units between the anisometropicand strabismic animals. However, dif-ferences in cortical neuronal unit responsetended to follow a continuum related toseverity of behaviorally measured depth ofamblyopia. Although the reduction ofcortical binocularly excited units wasslightly greater in the strabismic animals,the overall physiological changes in cellularresponse were more directly correlated tothe severity of the amblyopia rather thanthe etiology of the visual loss.

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Although some of the above resultsmay suggest that there had been shrinkagein the size of the ocular dominance columnsin response to the experimental alterations,a number of studies indicate that someforms of amblyopia might not result inshrinkage of the ocular dominance col-umns (11,33).

These results are not in fundamentaldisagreement with the pioneering studies ofHubel & Wiesel and others that foundshrinkage of ocular dominance columns inexperimental amblyopia. In those earlyexperiments, visual deprivation was total,achieved by suturing one eyelid closed orenucleation. Hence, there is a significantdifference between total deprivational visualdeficits and amblyopia secondary to eitherform degradation or spatial dislocation.

Other approaches that have beenused to assess functional abnormalities inamblyopia include high resolution magneticresonance imaging (MRI), blood-oxygen-level-dependent functional magnetic reso-nance imaging ( BOLD fMRI), positronemission tomography (PET), and brainsingle positron emission tomography(SPECT). Kabasakal & co-workers (37)tested ten patients, aged 8-14 years, withknown amblyopia (not specified as eitherstrabismic or anisometropic) using SPECTscans. While visually stimulating one or theother eye, patients were injected with aTechnitium-labeled marker and imaged 20-30 minutes later. In all cases, they foundgreater occipital cortex activity ac-cumulation when the normal eye wasstimulated, as compared to the amblyopiceye. Demer & co-workers (6), using PETimaging, found that cortical blood flow andglucose metabolism were reduced in theprimary visual cortex when monocularstimulation was applied to the amblyopiceye relative to stimulation of the non-amblyopic eye in strabismic amblyopia.Comparing the above two studies, PETscanning has better spatial resolution thanSPECT scanning, although the clinicalutility may not be practical or cost-effectivein either case.

Evaluating normal and amblyopic eyeresponses to different contrast sensitivitystimuli, Goodyear & colleagues (38), usingBOLD fMRI,[proper name of this procedure,NOT just an overlooked font change = Blood

Oxygenation Level Dependent-Ed] found aconsistently reduced level of stimulus-evoked response in areas of visual cortexwhen the amblyopic eye was stimulated asopposed to the response to the fellow eyestimulation.

In an effort to improve the resolutionof neuroimaging methods, Goodyear & co-workers (39) used high-resolution fMRI toevaluate visual cortex response in humanamblyopia. They found that, in adultpatients with a history of early onsetamblyopia, greater responses were found inareas cor-responding to the unaffected eyeversus the amblyopic eye. On the contrary,in two adult patients with later onsetamblyopia, a shift in ocular dominancecolumns was not noted, further supportingthe studies above, which suggest that,outside of the critical period of early visualdevelopment, ocular dominance columnsare relatively static anatomically, despitereduced response to amblyopia eye stimu-lation. Choi & co-workers (5) found similarresults of reduced activity in response toamblyopic eye stimulation, using fMRI inamblyopic patients ranging from 5-23 yearsof age.

DIFFERENCES Between Anisometropic and Strabismic AmblyopiaVISUAL PATHWAYS

A number of studies have foundfeatures of visual system structure andfunction that differ based upon the etiologyof the amblyopia (11,33,36). It follows thatbecause anisometropia generates aninterocular discrepancy in form vision andstrabismus generates a discrepancy inspatial localization, different processingpathways may be affected or preserved.Further, studies that have induced visualloss by deprivation (e.g., lid closure, cornealscarring (21,32)) may identify totally dif-ferent alterations in visual function.

In this study, there were somecontrasts between anisometropic ambly-opia and strabismic amblyopia such asstereopsis, pre-treatment visual acuity inthe amblyopic eye, final visual acuity in thenon-amblyopic eye and interocular LogMARline visual acuity difference at the start, butnot the end of treatment. However, for themost part, there were no “statisticallysignificant” differences between the groups,especially in terms of presence and size of

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SLO-mapped scotomata.

Although not found or demonstratedin the current study, amblyopic scotomatamay also be qualitatively different inanisometropic amblyopia as opposed tothose scotomata in strabismic amblyopia.Abrahamsson & Sjostrand (40), usingcontrast sensitivity measurements, foundthat, although all amblyopic patients haddeficits in the contrast sensitivity function,the strabismic amblyopia patients had agreater visual acuity loss in relation tocontrast sensitivity deficits than did theanisometropic amblyopia patients.

Histological findings in the lateralgeniculate nucleus also differ betweenstrabismic and anisometropic amblyopia inhuman and monkey. That is, both mon-ocular and binocular cell regions wereshrunken in the LGN in aniso-metropicamblyopia, whereas binocularly innervatedcellular regions were exclus-ively affected instrabismic amblyopia (10,41).

Functional magnetic resonance im-aging findings showed a difference amongpatients with anisometropic amblyopia(interocular refractive error difference of 3.0diopters or more) compared to those withstrabismic amblyopia (deviation 15Î ormore)(5). Assessing calcarine activation inresponse to checkerboard stimuli ofdifferent sizes and different temporalfrequencies, Choi & colleagues (5) foundthat calcarine activation was moresuppressed in anisometropic-induced am-blyopic eyes at higher spatial frequencywhile responses were more suppressed atlower spatial frequencies in strabismicamblyopia patients. These findings suggestthat there may be fundamental differencesin the spatial-temporal characteristicsbetween anisometropic and strabismicamblyopia by the time the ocularinformation reaches the calcarine fissure.

Amblyopic Scotoma in the "Normal" EyeFinding a relative scotoma in the non-

amblyopic eye in 20 of 26 patients withanisometropic amblyopia and all 20 of thestrabismic amblyopia patients was un-expected. Many studies of amblyopiaroutinely refer to the non-amblyopic eye as"normal", "sound", or "unaffected". However,the advent of tools to assess visual functionbeyond clinical visual acuity has previously

found some abnormalities in the fellow eyeof amblyopic patients.

Furthermore, in some patients, thesescotomata were present in one or both eyesAFTER what appears in all standard regardsto have been 100% successful treatment ofthe amblyopia including normal visualacuity in both eyes and normal binocularcooperation as evidenced by a normalstereoacuity of 40 seconds of arc. So wemay think we are in these best cases fully“curing” these children of their affliction.But the SLO tells us that that in mostpatients that is not true. Yes, in some caseswhich were clinically “cured”there were noscotomata in the normal non amblyopic eyeafter successful completion of treatment.But for the majority, it appears rather thatthere residual abnormalities in the uppervisual pathways, which limit visual functionprobably permanently, albeit so mildly thatthe impediment is undetectable by con-ventional clinical testing of standard visualparameters.

Paralleling, perhaps predicting, theSLO findings in this study, Rogers & col-leagues (42,43), while measuring contrastsensitivity in amblyopic children, found thatthe contrast sensitivity function (CSF) wasreduced in the amblyopic eye even thoughthat eye had achieved, with treatment, avisual acuity of 20/20. Their findings ofdiminished CSF in the fellow presumed"normal" eye of amblyopic patients aftersuccessful treatment of a contralateralamblyopia were not seen in their normalcontrol patients. The decreased CSF wasnot induced by amblyopia treatment withocclusion. In fact, as the amblyopic eyevisual acuity improved with treatment, theCSF in the non-amblyopic eye improvedalso. Thus, in both untreated and "suc-cessfully" treated unilateral functionalamblyopia, the non-amblyopic eye is stillnot entirely normal.

In a followup study investigating thisfinding, Leguire and colleagues (43) foundthat there was a correlation between CSFfrequency response and binocularity. Theyfound greater (better) binocularity whenthere were smaller differences in CSFbetween the eyes and lesser (poorer)binocularity when interocular CSF differ-ences were greater. Thus, these factors mayall inter-relate in terms of necessary criteria

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for binocularity such that normal binocularalignment promotes lesser interocular CSFdiscrepancy and, hence, greater binocularinteraction. This is supported by the greaterdegrees of binocularity noted in theanisometropic patients in this, our study,also. Because so many visual corticalneuronal units are driven binocularly, it isreasonable to assume that the non-amblyopic eye might be affected by theamblyopic eye, as was proposed by Leguire(43). Disruption of binocularity by abnormalinput from one eye would alter the functionof binocularly driven cortical cells andthereby alter the measurable function of thefellow eye.

Other studies have also foundabnormalities in the "normal" fellow eye ofunilaterally amblyopic patients. SeeRentschler & Hilz (44) who reported thatorientation sensitivity was abnormal innot only the amblyopic eye, but also inthe non-amblyopic presumed normalfellow eye of strabismic patients.

The current study provides furtherevidence that the "normal" eye may not betruly normal in amblyopia. Leguire & col-leagues (43) also followed CSF sensitivitybefore, during and upon completion ofocclusion therapy.

This current study assessed all pa-tients retrospectively and by SLO only atmost recent followup after completion ofamblyopia treatment. Thus, it is not knownfrom our study whether there were changesin scotoma size in either eye during eitheramblyopia treatment. This then wouldindeed be the next research step in theinvestigation of SLO scotomata in ambly-opia.

Other Study LimitationsWhile helpful in exploring the nature

of amblyopia of different etiologies, some ofthe clinical approaches mentioned above,including that of this study using the SLO,suffer from technical limitations, par-ticularly in data precision and resolution.Foremost among these is the age range ofthe patients of greatest interest. While someaspects of visual function in amblyopia canbe assessed in more mature children andadults, important information would begained by using "adult" techniques toanalyze visual functional abnormalities of

the early, developing visual system. Also,some of the tests were psychophysical innature and, thus, will have some limitationof accuracy, especially in children. Psycho-physical studies do not lend themselves toprecise localization of the defect responsiblefor features of amblyopia in that the stim-ulus response represents the summated re-sponses of the entire visual system, in-cluding higher order cognitive functions.

There are other limitations in thisstudy, especially in the use of the SLO toevaluate features of amblyopia. The currentstudy was retrospective, with data analysisat the end of followup after amblyopiatreatment was felt to be clinically stable. Asa result, while entry criteria were relativelyuniform, amblyopia treatment approachesand specifics varied considerably amongpatients, as it does in any normal clinicpractice, being readily adapted to eachindividual child and/or family. Further-more, as in any study of amblyopia, sincetreatment is carried out primarily by theparents and at home, treatment compliancecannot be really accurately assessed. Whileeach child in this group of patients was feltto have good treatment compliance, thiscould not be quantified. Indicative of lessthan perfect compliance is the fact that anumber of patients had a change intreatment modality (occlusion to atropine orvice versa), and this was usually basedupon issues of comfort and compliance.

The depth of the amblyopia was, insome patients, an underestimate. That is,there were four patients in whom the initialdiagnosis of amblyopia was made while thechild was still preverbal. Treatment wasinitiated and numerical visual acuity dataonly registered when the child becameverbally cooperative later. Hence, a smallnumber of patients may have had initialamblyopic eye visual acuity poorer thanwhat was ultimately quantitatively testedand recorded.

Another limitation is that the patientselection process was not random. Whilethere were certain criteria for inclusion inthe data analysis, patients were chosen toperform the SLO only if the child's per-formance at the slit lamp biomicroscopesuggested that the child was sufficientlycooperative to perform the SLO test. Thisobviously eliminated younger patients.

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Furthermore, further selection bias couldresult if there were a correlation between achild's performance in our clinical settingand overall child and family compliancewith treatment recom-mendations.

However, many aspects of the SLOtesting, by virtue of the testing procedureitself, are very precise. Because micro-perimetry is performed while monitoring alive image of the macula, stimulus locationwas extremely accurate. Also, rather thanrelying on a computerized paradigm toassess fixation reliability, as is done inautomated perimetry, the real-time moni-toring of the macula assured that stimuliwere not delivered unless fixation was ontarget.

Finally, the SLO data collection issimilar to that obtained with the Goldmannperimeter. That is, the examiner performingthe testing must identify levels of sensitivityand actively engineer a map of the sco-tomatous area based upon a finite numberof testing points. The legitimacy of the datagenerated in this study was facilitated bythe fact that the SLO was performed by anindividual skilled in the testing and maskedto all clinical information about the patientsexcept name and age. By far, the mostaccurate data were generated by thecomputer-assisted measurement of thescotoma area, once it was plotted by theperimetrist. Such great precisional comp-utational capability far exceeded theprecision of the human scotoma mappingprocedure.

REFERENCES

1. von Noorden GK. Binocular Vision and Ocular Motility.Mosby, St Louis 1990; 208. 2. National Eye Institute Office of Biometry andEpidemiology. Report on the National Eye Institute's VisualAcuity Impairment Survey Pilot Study. Department of Healthand Human Services, Washington DC; 1984. 3. Simons K . Preschool vision screening: Rationale,methodology and outcome. Surv Ophthalmol 1996; 41:3-30. 4. Attebo K, Mitchell P, Cumming R, Smith W, Jolly N,Sparkes R. Prevalence and causes of amblyopia in an adultpopulation. Ophthalmology 1998; 105:154-159. 5. Choi MY , Lee K-ML, Hwang J-M et al. Comparisonbetween anisometropic and strabismic amblyopia usingfunctional magnetic resonance imaging. Br J Ophthalmol2001; 85:1052-1056. 6. Demer JL, von Noorden GK, Volkow ND, Gould KL.Imaging of cerebral blood flow and metabo lism in amblyopiaby positron emission tomography. Am J Ophthalmol 1988;105:337-347. 7. Wiesel TN, Hubel DH. Effects of visual deprivation onmorphology and physiology of cells in the cat's lateral

geniculate body. J Neurophysiol 1963; 26:978-993. 8. Wiesel TN, Hubel DH. Single-cell responses in striate cortexof kittens deprived of vision in one eye. J Neurophysiol 1963;26:1003-1017. 9. von Noorden GK, Middleditch PR. Histology of the monkeylateral geniculate nucleus after unilateral lid closure andexperimental strabismus: Further observations. InvestOphthalmol 1975; 14:674-683.10. von Noorden GK, Crawford MLJ, Levacy RA. The lateralgeniculate nucleus in human anisometropic amblyopia. InvestOphthalmol Vis Sci 1983; 24:788-790.11. Horton JC, Stryker MP. Amblyopia induced byanisometropia without shrinkage of ocular dominance columnsin human striate cortex. Proc Natl Acad Sci USA 1993;90:5494-5498.12. Anton A, Yamagishi N, Zangwell L, Sample PA, WeinrebRN. Mapping structural to functional damage in glaucoma withstandard automated perimetry and confocal scanning laserophthalmoscopy. Am J Ophthalmol 1998; 125:436-446.13. Ahn B-S, Kee C. Ability of a confocal scanning laserophthalmoscope (TopSS) to detect early glaucomatous visualfield defect. Br J Ophthalmol 2000; 84:852-855.14. Mori F, Ishiko S, Kitaya N et al. Scotoma and fixationpatterns using scanning laser ophthalmoscope microperimetryin patients with macular dystrophy. Am J Ophthalmol 2001;132:897-902.15. Haritoglou C, Ehrt O , Gass CA, Kristin N, Kampik A.Paracentral scotomata: A new finding after vitrectomy foridiopathic macular hole. Br J Ophthalmol 2001; 85:231-133.16. Sunness JS, Bressler NM, Maguire MG. Scanning laserophthalmoscopic analysis of the pattern of visual loss in age-related geographic atrophy of the macula. Am J Ophthalmol1995; 119:143-151.17. Fujii GY, De Juan E, Humayun MS, Sunness JS, Chang TS,Rossi JV. Characteristics of visual loss by scanning laserophthalmoscope microperimetry in eyes with subfovealchoroidal neovascularization secondary to age-related maculardegeneration. Am J Ophthalmol 2003; 136:1067-1078.18. Sabates NR, Crane WG, Sabates FN, Schuchard RA,Fletcher DC. Scanning laser ophthalmoscope macular perimetryin the evaluation of submacular surgery. Retina 1996; 16:296-304.19. Fletcher DC, Schuchard RA. Preferred retinal locirelationship to macular scotomas in a low vision population.Ophthalmology 1997; 104:632-638.20. Schuchard RA, Naseer S , de Castro K. Characteristics ofAMD patients with low vision receiving visual rehabilitation.J Rehabil Res Dev 1999; 36:294-302.21. Fletcher DC, Schuchard RA, W atson G. Relative locationsof macular scotomas near the PRL: Effect of low visionreading. J Rehabil Res Dev 1999; 36:356-364.22. Holladay JT , Prager TC. Mean visual acuity. Am JOphthalmol 1991; 111:372-374.23. Sunness JS, Schuchard RA, Shen N, Rubin GS, Dagnelie G,Haselwood DM. Landmark-driven fundus perimetry using thescanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci1995; 36:1863-1874.24. Simons K, Gotzler KD, Vitale S. Penalization versus part-time occlusion and binocular outcome in treatment ofstrabismic amblyopia. Ophthalmology 1997; 104:2156-2160.25. Pediatric Eye Disease Investigator Group. A randomizedtrial of atropine vs patching for treatment of moderateamblyopia in children. Arch Ophthalmol 2002; 120:268-278.26. Fioretto M, Gandolfo E, Burtolo C et al. Evaluation ofamblyopic scotoma by electrophysiological examinations andcomputerized perimetry. Eur J Ophthalmol 1996; 6:201-207.27. von Noorden GK. Histological studies of the visual systemin monkeys with experimental amblyopia. Invest Ophthalmol1973; 12:727-738.28. Wiesel TN, Hubel DH, Lam DNK. Autoradiographic

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demonstration of ocular dominance columns in the monkeystriate cortex by means of transneuronal transport. Brain Res1974; 79:273-279.29. LeVay S, Hubel DH, Wiesel TN. The pattern of oculardominance columns in macaque visual cortex revealed by areduced silver stain. J Comp Neurol 1975; 159:559-576.30. LeV ay S, Connolly M, Houde J, Van Essen DC. Thecomplete pattern of ocular dominance stripes in the striatecortex and visual field of the macaque monkey. J Neurosci1985; 5:486-501.31. Hubel DH, Wiesel TN. The period of susceptibility to thephysiological effects of unilateral eyelid closure in kittens. JPhysiol (Lond) 1970; 206:419-436.32. Hubel DH , Wiesel TN, LeVay S. Plasticity of oculardominance columns in the monkey striate cortex. Philos TransR Soc Lond B Biol Sci 1977; 278:377-409.33. Horton JC, Hocking DR, Kiorpes L. Pattern of oculardominance columns and cytochrome oxidase activity in amacaque monkey with naturally occurring anisometropicamblyopia. Vis Neurosci 1997; 14:681-689.34. Hendrickson AE, Hunt SP, Wu J-Y. Immunocytochemicallocalization of glutamic acid decarboxylase in monkey striatecortex. Nature 1981; 292:605-607.35. Horton JC, Hedley-Whyte ET. Mapping of cytochromeoxidase patches and ocular dominance columns in human visualcortex. Philos Trans R Sco Lond B Biol Sci 1984; 304:255-272.36. Kiorpes L, Kiper DC, O'Keefe LP, Cavanaugh JR, MovshonJA. Neuronal correlates of amblyopia in the visual cortex ofMacaque monkeys with experimental strabismus andanisometropia. J Neurosci 1998; 18:6411-6424.37. Kabasakal L, Devranoglu K, Arslan O et al. Brain SPECTevaluation of the visual cortex in amblyopia. J Nucl M ed 1995;36:1170-1174.38. Goodyear BG, Nicolle DA, Humphrey GK, Menon RS.BOLDfMRI response of early visual areas to perceived contrastin human amblyopia. J Neurophysiol 2000; 84:1907-1913.39. Goodyear BG, Nicolle DA, Menon RS. High resolutionfMRI of ocular dominance columns within the visual cortex ofhuman amblyopes. Strabismus 2002; 10:129-136.40. Abrahamsson M , Sjostrand J . Contrast sensitivity and acuityrelationship in strabismic and anisometropic amblyopia. Br JOphthalmol 1988; 72:44-49.41. von Noorden GK, Crawford MLJ. Form deprivation withoutlight deprivation produces the visual deprivation syndrome inMacaca mulatta . Brain Res 1977; 129:37-44.42. Rogers GL, Bremer DL, Leguire LE. The contrastsensitivity function and childhood amblyopia. Am JOphthalmol 1987; 104:64-68.43. Leguire LE, Rogers GL, Bremer DL. Amblyopia: Thenormal eye is not normal. J Pediatr Ophthalmol Strabismus1990; 27:32-38.44. Rentschler I, Hilz R. Abnormal orientation selectivity inboth eyes of strabismic amblyopes. Exp Brain Res 1979;37:187-191.

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ABSTRACT: Purpose: To investigate the long-term vision outcomes of amblyopiatreatment in “successfully”, compared with “unsuccessfully”, treated patients. Methods: Forty-two participants (n=42, mean age 14.8 years, range 10-25years) were enrolled in the study. Individuals with strabismic or mixed (strabismicand anisometropic) amblyopia were examined at a mean of 6.6 years (range 1-18years) after cessation of amblyopia treatment. Participants were classified as being“successfully” treated (Group 1) if visual acuity of 6/7.5 or better was achieved atcessation of treatment, or “unsuccessfully” treated (Group 2) if visual acuity of 6/9or less was achieved at cessation of treatment. Visual acuity was analyzed bycalculating an interocular score or difference in visual acuity between theamblyopic and non amblyopic normal (control) eye. Results: A deterioration of visual acuity occurred in 62% or the participants inboth Groups 1 and 2. The mean deterioration of visual acuity over time for eithergroup was less than one LogMAR chart line and was not "statistically significant"by convention (F [1,39] = 3.361, p=0.074). The outcomes achieved at cessation oftreatment did not "statistically significantly" affect the mean deterioration thatoccurred over time (F [1,49] = 0.031, p=0.860). Conclusion: Visual acuity was relatively stable over a mean followup periodof 6.6 years. The treatment outcome and the success of amblyopia treatment werefound to be irrelevant to long term stability of visual acuity. These findings suggestthat amblyopia treatment mostly results in a lasting improvement in visual acuity,and that both unsuccessfully and successfully treated individuals maintain theirvisual acuity improvement achieved during treatment.

Original Scientific Article

Long-Term Vision Outcomes of Conventional Treatment of Strabismic and AnisometropicFunctional Amblyopia

PAM GAROUFALIS, BOrth(Hons)1,ZORAN GEORGIEVSKI, BAppSc(Orth)Hons1,2 and KONSTANDINA KOKLANIS, PhD1,3

from 1Department of Clinical Vision Sciences, La Trobe University, 2Northern Hospital and 3Royal Children's Hospital, Melbourne, Australia

Received for consideration August 5, 2006; accepted for publication November 7, 2006.

Correspondence/complimentary reprint requests to Zoran Georgievski, BAppSc(Orth)Hons, Dept ClinicalVision Sciences, La Trobe University, Victoria 3086, Australia. Fax: 61-3-9479-5784. email: [email protected]

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INTRODUCTION

Amblyopia affects between 1-4% of thepopulation and is the most common form of visionimpairment in children (1,2). In 1997, theeffectiveness of amblyopia treatment in Great Britainwas questioned by a report published by the NationalHealth Service Center for Reviews andDissemination (UK) (3). Specifically, and in fact, thisreport revealed primarily a lack of quality studies onthe long-term effectiveness of amblyopia treatment.On the basis of this and other findings, the authorsconcluded that pre-school vision screening should beceased.

Reports of deterioration in vision ofsuccessfully treated amblyopes vary widely in theliterature. Studies indicate that between 17% and76% of successfully treated amblyopes showregression in visual acuity at long-term followup (4-12). One of the earliest studies (5) reported that themajority of amblyopes lost approximately half of thevision improvement achieved during treatment, while17% regressed to original pre-treatment levels. Morerecent studies have reported less deterioration, butvariability amongst the results continues to exist. Forinstance, while Ohlsson et al (10) found that visualacuity regressed in only 17% of amblyopic eyes at anaverage followup period of 10.4 years, Rutstein &Corliss (13) and the Pediatric Eye DiseaseInvestigator Group (PEDIG) (14) recently reportedsomewhat higher rates. The PEDIG found that 24%of strabismic and anisometropic amblyopes with a 1year followup regress, while Rutstein & Corlissfound regression in 35% of a similar amblyopicpopulation with a mean followup of 8.2 years. Thedifferences in the literature are possibly due to factorssuch as the inclusion or exclusion of amblyopeswhose monitoring ended prior to 9 years of age,different followup periods, inconsistent definitions ofamblyopia and a lack of controls for visual acuitymeasurements.

There has also been a lack of controls for thevariables: (the) effects of practice and maturation.The need to control for maturation effects inlongitudinal studies was highlighted by Levartovskyet al (7) who reported that while visual acuitydeteriorated in 53% of amblyopic eyes, it alsoactually improved in 36% of amblyopic eyes afterocclusion treatment had ceased. They suggested thatthis was due to the older age of the patients and theirimproved cooperation with the visual acuity test atlong-term followup. In order to reduce these effectsof maturation associated with longitudinal studies,visual acuity ratios that incorporate the non-amblyopic eye as a control for this factor should beused (4). However, only one study (4) has utilizedthis concept of interocular difference wheninvestigating the regression of visual acuity inamblyopic patients. All other studies to date have

analyzed vision outcomes for the amblyopic and non-amblyopic eyes separately.

To date, studies have also neglected toinvestigate the long-term stability of visual acuity inunsuccessfully treated patients. Studies on the naturalhistory of untreated patients with amblyopia havereported that deterioration of visual acuity does occurover time (15,16). On this basis, Ohlsson andcolleagues (10) suggest that theoretically successfultreatment of amblyopia could result in a"normalization" of the development of the amblyopiceye. If this is the case, unsuccessfully treated patientsmay show greater regression of vision thansuccessfully treated amblyopes.

The aim of this study was to investigate thelong- term vision outcomes of occlusion treatment inpatients with successfully and unsuccessfully treatedamblyopia. To do this, we compared the meaninterocular visual acuity score achieved at cessationof treatment with that obtained at a long-termfollowup visit.

SUBJECTS and METHODS

Forty-two (n=42) individuals were includedin this study. Participants were divided into twogroups, successfully treated and unsuccessfully treatedamblyopia. Group 1 comprised the successfullytreated amblyopes. This outcome ("success") wasdefined as a visual acuity of 6/7.5 (20/25) or better atthe cessation of treatment. Group 2 comprised theunsuccessfully treated amblyopes. This includedthose for whom this result may have been due to alack of compliance with treatment. This outcome wasdefined as a best corrected visual acuity of 6/9(20/30) or less at the cessation of treatment.

These participants were recruited from aprivate pediatric ophthalmology clinic. Patients wereinvited to participate if they had documentedevidence of strabismic and/or anisometropicamblyopia, had undertaken amblyopia treatment andhad been monitored until at least 9 years of age. Allparticipants had ceased amblyopia (or any"maintenance") treatment at least 12 months prior toinclusion and final visual acuity examination.Individuals with ocular disease or manifestnystagmus were excluded from this study. In total, 90patients satisfied the inclusion criteria and wereinvited to participate in this study, 42 of whichresponded positively and constitute our study groups.

For the purposes of this study, amblyopia wasdefined as an interocular difference in visual acuity ofat least 2 lines on the visual acuity eye chart, with theamblyopic eye having a recorded level of visualacuity of 6/12 (20/40) or less. Strabismus was definedas any manifest binocular deviation andanisometropia as an interocular difference in

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refraction of at least 1 diopter spherical equivalentbetween the two eyes.

All participants were examined by a singleexaminer at what was termed the [study final]followup visit. The examiner was blind to thepreviously documented visual acuity measurementfor each participant. At this followup visit, eachparticipant's best corrected visual acuity wasmeasured using a 3 meter Bailey-Lovie letter chartand a 6 meter Snellen chart, with chart illuminationmaintained at 150cd/m2. The right eye was alwaystested first, so that consequently the amblyopic eyewould be randomly assessed in the order ofexamination. The participant was asked to read eachline in reverse order with the left eye in order tocounteract practice effects. The examiner encouragedthe participant to read as far down the chart aspossible and the visual acuity was taken as thesmallest line read with correct identification of 50%+1 of the characters, as reported in the literature (17).Visual acuity was recorded as the reciprocal of thelogMAR (log to base 10 of the minimum angle ofresolution for the given optotype), and included creditfor every letter read correctly,to allow finerdifferentiation between acuity scores and to facilitatestatistical analysis (18). The interocular score wasthen calculated by subtracting the visual acuity scoreof the amblyopic eye from the non-amblyopic eye.This interocular score was calculated for two pointsin time, at cessation of amblyopia treatment and atthis [study final] followup visit. The type of visionchart used for scoring and analysis was kept constantover time. For example, if the chart used at thecessation of treatment was a Snellen chart, the samechart was used to measure visual acuity at the long-term followup visit. A two-way mixed analysis of co-variance (ANCOVA) was used for these statisticalevaluations. The mean period since cessation oftreatment was chosen as the co-variant so as to reduceany variability introduced by the time of the followupperiod. The results were considered "statisticallysignificant" (by convention) when the p (probability)value was #0.05.

To detect the presence of strabismus, a [single]cover test was performed for near and distance usingan accommodative target. Information regarding theparticipant's age and visual acuity at commencementof amblyopia treatment, age and visual acuity atcessation of amblyopia treatment were obtained frommedical records. The Student t-test and a chi-squarewere used to analyze the data. Results wereconsidered "statistically significant" (by convention)when the p (probability) value was #0.05.

RESULTS

Forty-two participants (n=42; 26 females, 16males) with a mean age of 14.8 years (range 10-25years) were examined. Twenty-six participants wereconsidered to be successfully treated (Group 1) and16 were considered unsuccessfully treated (Group 2).

Fifty percent of the participants in Group 1 and75% of those in Group 2 had strabismic amblyopia.The remaining 50% of participants in Group 1 and25% in Group 2 had mixed (strabismic andanisometropic) amblyopia, and none hadanisometropic amblyopia alone (that is, without atleast microtropia). There was no "statisticallysignificant" difference in the type of amblyopiabetween the two groups (x2(1) = 1.637, p=0.201[Yates' correction]).

Table 1 below shows the mean age of theparticipants, period of followup since cessation andduration of treatment. The participants inUnsuccessful Group 2 were "statisticallysignificantly" older (t[21.5] = -3.194, p=0.004) andhad "statistically significantly" longer periods (andlater times and ages) of followup than those inSuccessful Group 1 (t[24.4] = -2.853, p=0.009). Theoverall mean followup for all participants was 6.6years. There was not a "statistically significant"difference for mean duration of treatment between thetwo groups (t[40] = 0.599, p=0.553).

At long-term [final study] followup, 62% ofparticipants in Group 1 and 62% of participants in

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Group 2 demonstrated deterioration in their ambly-opic eye visual acuity since cessation of treatment(see Figure 1, above^). In Successful Group 1, 23%showed no change in visual acuity and the remaining15% had an apparent improvement in visual acuity ofthe amblyopic eye at the time of the [final study]followup visit. In unsuccessful Group 2, 19% had nochange in visual acuity and the remaining 19% hadimprovement.

Group 1: Successfully Treated Amblyopia

In this group, at cessation of occlusion treatment,the mean logMAR visual acuity scores for theamblyopic and non-amblyopic eyes were 1.04 (6/75+ 2 letters) and 1.19 (6/4.8 -0.5 letter), respectively.At long-term followup, the mean logMAR visualacuity scores for the amblyopic and non-amblyopiceyes were 1.02 (6/7.5 + 1 letter) and 1.22 (6/48 + 1

letter), respectively. When comparing the mean VAscores over time, there appears to have been minimalchange; the amblyopic eye declined by 1 letter andthe non-amblyopic eye improved by 1.5 letters.

The mean interocular score at cessation oftreatment was 0.12 (1.2 lines), while at the long-term[study final] followup visit it was 0.20 (2 lines) (SeeTable 2, below). The interocular score indicates apost-treatment decline in visual acuity at the [studyfinal] followup visit of approximately 0.08 (0.8 lines,representing 4 letters).

Group 2: Unsuccessfully Treated Amblyopia

In Group 2, at cessation of occlusiontreatment, the mean logMAR visual acuity scores forthe amblyopic and non-amblyopic eyes were 0.72(6/15 +2 letters) and 1.09 (6/6 -0.5 letters),respectively. At long-term [study final] followup, themean logMAR visual acuity scores for the amblyopic

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and non-amblyopic eyes were 0.68 (6/15 -l letter) and1.12 (6/6 +1 letter) respectively. Again, as for Group1, when comparing the post-treatment mean visualacuity scores over time, there appears to have beenminimal change; the amblyopic eye visual acuitydeclined by 3 letters and the non-amblyopic eyeimproved by 1.5 letters.

The mean interocular score at cessation oftreatment was 0.37 (3.7 lines). The mean interocularscore at the long-term followup visit was 0.45 (4.5lines) (See Table 3, above). The [study final]interocular score for the amblyopic eye indicates a

decline in visual acuity at the followup visit ofapproximately 0.08 (0.8 lines, again representing 4letters).

Comparison of Groups 1 & 2

Overall, unsuccessful Group 2 showed a largermean interocular score (difference) than SuccessfulGroup 1 at both cessation of amblyopia treatment andat the long-term [study final] followup visit (seeFigure 2, below). Both groups achieved an increase inthe interocular score over time; this approached, butfailed to reach, "statistical significance" for either

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group (F[1,39] = 3.361, p=0.074). There was no"statistically significant" difference in the interocularscore over time between the two groups (F[1.39] =0.031, p=0.860).

DISCUSSION

Sixty-two percent of participants in both Groups1 and 2 demonstrated a decline in visual acuity of theamblyopic eye at the [study final] followup visit. Thisconcurs with earlier published studies, which havereported that more than half of successfully treatedamblyopes will show visual deterioration in theamblyopic eye after cessation of treatment (5,7,9).The amount of visual deterioration over time was, inthis study, less than one line on the logMAR chart.These findings are similar to those reported by Chinget al (4) and Rutstein & Corliss (13), but are less thanthose reported by other earlier studies (9,12). It isnoteworthy, however, that these other earlier studiesincluded participants that had ceased monitoringvision prior to 9 years of age, and children whosemonitoring ends before this age have been reported toshow a greater deterioration of vision in theamblyopic eye(7).

A visual acuity deterioration of less than one linewas neither "statistically significant" nor, in ourestimation, clinically significant. The small changesin vision in the amblyopic eye observed over time,which included both improvement and deterioration,is most likely due to variable inter-examinerreliability, which has been reported to vary from 0.10(19) to 0.24 (20) logMAR units. Visual acuitymeasurements at the cessation of occlusion treatmentand at the [study final] followup visit were made bydifferent examiners. The observed greater tendencyfor the interocular score to increase over time couldbe due to as simple a matter as the examiner in thepast not trying to "push" the participants beyond the6/6 line. [Sadly, this is an all too common clinicalpractice anyway. But now that the corneal andrefractive surgeons are providing their patientsregularly better than 6/6 and 20/20, these visions will nolonger be "good enough" and it will become routine touse the 20/15 = 6/4.5 and 20/10 =6/3 lines on our eyecharts -Ed] This possibility and explanation is furthersupported by the fact that the non-amblyopic eye inboth groups showed a mean improvement in visualacuity over time. On closer inspection of the results,13 out of the 42 cases were recorded to have a levelof visual acuity of 6/6 in the non-amblyopic eye atcessation of treatment. This often improved to betterthan 6/6 at the followup visit. This is an inherentlimitation of the retrospective nature of such a studyas this is. However, similar testing conditions andidentical vision charts were used at both visits tominimize this problem of variability as much aspossible.

We also found that both the proportion of patients

showing deterioration in amblyopic eye visual acuityand the level of deterioration was similar for thesuccessfully and unsuccessfully treated patients. Incontrast, Simons & Preslan (16) reported thatuntreated or non-compliant patients weresignificantly more likely to have poorer visionoutcomes than those whose amblyopia was treated.Similarly, Haase & Wenzel (15) reported thatuntreated adults show significantly lower levels ofvisual acuity as compared to untreated children. Theysuggested that this is indicative of spontaneousworsening of amblyopia during adolescence.However, both these studies did not specificallycompare successful and unsuccessful amblyopiatreatment outcomes. Simons & Preslan (16)compared treated and untreated amblyopia, and non-compliant to compliant patients at various visualacuity levels, while Haase & Wenzel (15) onlyassessed untreated patients. Given that our findingsdiffer from these two studies, it is possible that thestability of vision in non-compliant or untreatedpatients (which we did not attempt to consider in thisstudy) is different to that of unsuccessfully treatedpatients. However, this is difficult to concludedefinitively by comparison, as some of the patients inour unsuccessfully treated group may have had pooroutcomes due to non-compliance rather than resistantamblyopia. Furthermore, the untreated patients inSimons & Preslan's study were under the age of 9years and only had a followup period of one year,while the cross-sectional nature of Haase & Wenzel'sstudy meant that variables other than amblyopia mayhave contributed to their findings.

Although neither statistically nor clinicallysignificant, we did find that the UNsuccessfullytreated group had a slightly greater level ofdeterioration than the Successfully treated group. Theunsuccessfully treated group had longer followupperiods that may have contributed to these findings.However, it should be reiterated that the differencewas not "statistically significant" Interestingly, theunsuccessfully treated group also had an overrepresentation of strabismic amblyopia (as opposedto mixed type). This is in contrast to the literature(21) but may be explained by the fact that mixedamblyopia may have been proportionally greater atthe commencement of treatment. Some studies havereported that anisometropia decreases with age(22,23). The participants in the unsuccessfully treatedgroup were also significantly older at the followupvisit than the successfully treated group, and thediagnosis of strabismic amblyopia may not havealways been the same diagnosis due to anisometropiadecreasing over time. That is, there may otherwisehave been more cases of mixed amblyopia. Previousstudies have also shown that patients with mixedamblyopia are more likely to show visualdeterioration over time than pure strabismic oranisometropic amblyopes (6,24).

In our study, approximately 23% of the amblyopes

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in Group 1 and 19% in Group 2 had an apparentimprovement in visual acuity. This improvement rateis lower than those reported by Leiba et al (8) (being50%), Levartovsky et al (7) (36%) and Ohlsson et al(10) (33%), but greater than the 15% improvementreported by Rutstein & Corliss (13). Levartrovsky (7)suggested that improvements in visual acuity weremost likely due to practice effects, rather than furthertherapeutic intervention, given that at long-termfollowup visits participants were older and better ableto cooperate with visual acuity testing. Theinterocular score was utilized in this study to controlfor these practice effects. However, this score willonly control for practice effects if the improvement invisual acuity is equal between the two eyes. Thisapparent improvement in visual acuity may also bepartly due to inter-examiner bias. Visual acuity scoresat cessation of treatment and at the long-termfollowup visit were determined by differentexaminers. The method employed to assess visualacuity in the past may have been different to themethod applied at the followup visit. A closerelationship has been found between visual acuityobtained and the testing criteria applied to assessvision (25); we attempted to reduce this source ofvariability by using the same type of vision chart andtesting distance as previously documented.

It is also possible that participants who were olderat the followup visit were more cooperative and moremotivated during the examination. In addition, thepossibility of an ongoing process of maturation of thevisual system cannot be excluded. The developmentof visual acuity has been suggested to peak in themid-twenties (19) and this improvement mayrepresent the continuation of this process.Furthermore, other studies have also reportedimprovements of visual acuity in the amblyopic eyeafter loss of the good eye in adults (26,27). Thissuggests that maturation of the visual system may bea gradual process that is not complete at the samestage in all individuals.

Overall, the utilization of the interocular score,instead of analyzing the amblyopic eye alone,allowed a more meaningful interpretation of visualacuity over time. Ching et al (4), who also reportedvisual acuity as a difference between the two eyes,found a much lower incidence of deterioration,approximately 22%. This lower rate may be due tothe their shorter followup period, which was only upuntil 12 to 13 years of age, and longer monitoringperiod, up until 10 years of age. However, their studyreported a level of deterioration of less than oneSnellen line, similar to the findings of our study.

CONCLUSION

Our study results show that visual acuity isessentially stable over a mean followup period of 6.6years and that amblyopia treatment results in a lastingimprovement in visual acuity, regardless of whethertreatment was deemed to be successful. Our findingsalso suggest that the long-term stability ofunsuccessfully treated amblyopia is similar to that ofsuccessfully treated amblyopia. Amblyopia treatmentshould therefore be encouraged as even short-termtreatment measures and results make a tangible long-term difference in adult populations.

REFERENCES

1. Preslan MW, Novak A. Baltimore vision screening project. Ophthalmology 1996; 103:105-109.

2. Williamson THA, Dutton GN. Assessment of an inner city visual screening programme for preschoolchildren. Br J Ophthalmol 1995; 79:1068-1073.

3. Snowden SK, Stewart-Brown SL. Preschool vision screening: Results of a systematic review. ReportNo. 9. York. NHS Centre for Reviews and Dissemination, University of York, 1997.

4. Ching FC, Parks MM, Friendly DS. Practical management of amblyopia. J Pediatr OphthalmolStrabismus 1986; 23:12-16.

5. Gregerson E, Rindziunski OT. Conventional occlusion in the treatment of squint amblyopia. A 10year followup. Acta Ophthalmol (Copenh) 1965; 43:462-474.

6. Levartovsky S, Gottesman N, Shimshoni M, Oliver M. Factors affecting long-term results ofsuccessfully treated amblyopia: Initial visual acuity and type of amblyopia. Br J Ophthalmol 1995;79:225-228.

7. Levartovsky S, Oliver M, Gottesman N, Shimshoni M. Factors affecting long-term results ofsuccessfully treated amblyopia: Age at beginning of treatment and age at cessation ofmonitoring. J Pediatr Ophthalmol Strabismus 1992; 29:219-223.

Binocular Vision & Long-Te rm Vis ion Ou tcom es of C onventiona l Tre atm en t of S trab ism ic & An isom etropic F unctiona l Am blyopia First Quarter of 2007Stra bism us Qu arte rly© P. Garoufal is, BOrth(Orth)Hons, Z. Georgievski BAppSc(Orth)Hons and K. Koklanis, PhD Volume 22 (No.1): 49-56

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8. Leiba H, Shimshoni M, Oliver M, Gottesman N, Levartovsky S. Long-term followup of occlusiontherapy in amblyopia. Ophthalmology 2001; 108:1552-1555.

9. Malik SRK, Virdi PS, Goel BK. Followup results of occlusion and pleoptic treatment. ActaOphthalmol (Copenh) 1975; 53:620- 625.

10. Ohlsson JL, Baumann M, Sjostrand JB, Abrahamsson M. Long-term visual outcome in amblyopiatreatment. Br J Ophthalmol 2002; 86:1148-1151

11. Scott WE, Dickey CF. Stability of visual acuity in amblyopic patients after visual maturity. Graefe'sArch Clin Exp Ophthalmology 1988; 226:1254-157.

12. Sparrow JC, Flynn JT. Amblyopia: A long-term followup. J Pediatr Ophthalmol 1977; 14:333-336.

13. Rutstein R, Corliss D. Long-term changes in visual acuity and refractive error in amblyopes. OptomVis Sci 2004; 81:510-515.

14. Group PEDIG. Risk of amblyopia recurrence after cessation of treatment. J AAPOS 2004; 8:420-428.

15. Haase W, Wenzel F. The natural course of untreated functional amblyopia: Does it progress betweenchildhood and adulthood? Binocul Vis Strabismus Q 1997; 12:17-24.

16. Simons K, Preslan M. Natural history of amblyopia untreated owing to lack of compliance. Br JOphthalmol 1999; 83:582-587.

17. Ferris FL, Kassoff A, Bresnick GH. New visual acuity charts for clinical research. Am J Ophthalmol1982; 94:91-92.

18. Kitchen J, Bailey I. Task complexity and visual acuity in senile macular degeneration. Aust J Optom1981; 64:235-242.

19. Frisen L, Frisen M. How good is normal visual acuity? A study of letter acuity thresholds as afunction of age. Graefe's Arch Clin Exp Ophthalmol 1981; 215:149-157.

20. Rosser DA, Laidlaw DA, Murdoch IE. The development of a "reduced logMAR" visual acuity chartfor use in routine clinical practice. Br J Ophthalmol 2001; 85:432-436.

21. Flynn JT, Schiffman J, Feuer W, Corona A. The therapy of amblyopia: An analysis of the resultsof amblyopia therapy utilizing the pooled data of published studies. Trans Am OphthalmolSoc 1998; 96:431-453.

22. Almeder LM, Peck LB, Howland HC. Prevalence of anisometropia in volunteer laboratory andschool screening populations. Invest Ophthalmol Vis Sci 1990; 31:2448-2455.

23. Gwiazda J. Refractive errors, amblyopia and development of the visual system in children. CurrentOpinion Ophthalmol 1991; 2:696-701.

24. Beardsell R, Clarke S, Hill M. Outcome of occlusion treatment for amblyopia., J Pediatr OphthalmolStrabismus 1999; 36:19- 24.

25. Vanden Bosch ME, Wall M. Visual acuity scored by the letter-by-letter or probit methods has lowerretest variability than the line assignment method. Eye 1997; 11:411-417.

26. Vereecken EP, Brabant P. Prognosis for vision in amblyopia after the loss of the good eye. ArchOphthalmol 1984; 102:220- 224.

27. Mallah MKE, Chakravarthy U, Hart PM. Amblyopia: Is visual loss permanent? Br J Ophthalmol2000; 84:952-956.

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A PREANNOUNCEMENT:

Binocular Vision & Strabology Report of the 2nd Pediatric Ophthalmology and Strabismus Day First Quarter of 2007Stra bism us Qu arte rly© An Extravaganza in Las Vegas, USA, Di rected by K. W r ight, MD Volume 22 (No.1):57-63

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Strabology Report: 2nd Pediatric Ophthalmology and Strabismus DayAn Extravaganza in Las Vegas, USA, November 10, 2006

Immediately Preceding the American Academy of Ophthalmology Annual Meeting

Meeting Reported by: Sonal Farzavandi, FRCS

Meeting Director: Kenneth Wright, M.D.

Organizing Committee: Sonal Farzavandi, FRCS, David Granet, M.D.,

Malcolm Ing, M.D., Elias Traboulsi, M.D., and

Miho Sato, M.D.

The charm and vibrancy of the funfilled casino city - Las Vegas - attracted 175ped i a t r i c oph th a l m o l o g i st s f ro m 30countries to attend the pre-AAO PediatricOphthalmology and Strabismus Day. Thisone day meeting, the second of its kind, washosted by the Wright Foundation forPediatric Ophthalmology and Strabismusand Alcon Laboratories Inc.

The meeting began with a breakfastsymposium on "Pediatric Cataract SurgeryTechniques". Following this, there were 3scientific sessions with free papers onstrabismus and 2 strabismus round tableswith exc i t ing case presentations anddiscussion. The pediatric ophthalmologyfree paper session was held in the afternoonand focused on ocu lar tumors, ROP,pediatric cataracts and IOL. There were 2round table sessions: "Ocular Tumors" and"Challenging Cases in Pediatric Ophththal-mology"

This report will review only thestrabismus papers presented at this meeting.

Scientific Session 1Richard Gardner, MD et al, from

Moorfields Eye Hospital, England, pre-sented a retrospective review of 58 patientswho were on long term botulinum toxininjections for strabismus. (Long termdefined as having more than 25 injections.)Exotropia was the most common deviationand the lateral rectus muscle was the mostfrequently injected muscle. He concludedthat botulinum toxin injections can be usefulon a long term basis in patients who havehad multiple previous strabismus surgeries,have poor binocular potential or who areunfit for surgery. The angle of deviationwas noted to decrease with time and the

interval between injections increased withtime. No serious adverse effects werereported with long term use.

An interesting discussion followedwith questions on mean time betweeninjections, and if the muscle looked anydifferent during surgery following long terminjections. Dr. Gardner stated that the meantime between injections was 6 months overthe whole group. The reason for decrease inthe angle and increase in the time intervalbetween injections was attributed to the factthat, over time, the fibers that dropped outwere mainly the singly innervated fibers.They are important in saccadic inductionand power. [Spencer RF, McNeer KW.Botulinum toxin paralysis of adult monkeyextraocular muscle. Structural alterations inorbital, singly innervated muscle fibers.Arch Ophthalmol 1987; 105:1703-1711].Intraoperatively, the muscle looked nodifferent when compared with other patientswho have had multiple surgeries.

Dr. M. Salah, from Saudi Arabia,studied the effect of adding inferior rectusrecession to inferior oblique recession forcorrection of esotropia and large V patternin cases with congenital bilateral superioroblique palsy presenting with a small anglee s o t r o p i a i n p r i m a r y p o s i t i o n . H ecommented that adding bilateral inferiorrectus recession will correct the bilateralfallen eyes, the large V pattern and thesmall angle esotropia in primary position.

Notable in this session was the paperby Irene Ludwig, MD, from the USA, ontrauma causing avulsion-type flap tear ofthe extraocular m uscles in 35 cases.

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Etiology included blunt trauma and post-retinal detachment repair. The key todiagnosis is the history, wherein the patientsoften have symptoms which are far worsethan the degree of head trauma. Clinically,it can mimic a pseudo-muscle palsy (tethercreated by torn flap) or pseudo-entrapment.The direction taken by the flap duringhealing determined the resultant strabismuspattern. Intraoperatively, one would see athin and narrow appearance of the attachedmuscle, lack of capsule or muscle encasedin orbital fat. Recognizing the tear andfinding the flap is not easy at first. Earlyrepair is advised using braided polyestersuture. Worst results were in cases withorbital fracture repair prior to presentation,those with prior attempts at strabismusrepair and those with delayed surgery. Bestresults were obtained with simultaneousfracture and strabismus repair or earlystrabismus repair alone.

Strabismus Round Table - AMary O'Hara, MD, from the USA,

presented a rare case of superior obliquepalsy in a dysgerminoma survivor. Asixteen year old female with bilateraloophorec tomy done for ovarian dys -germinoma presented 4 months postchemotherapy with frontal headache andvertical diplopia. MRI scan was normal.Clinically there was papilledema and a leftsuperior oblique palsy. She was diagnosedto have idiopathic intracranial hypertension.Normalization of the intracranial pressureresulted in resolution of the superior obliquepalsy.

This was followed by a magic showby David Granet, MD of the USA. Thismagic video show even outshined thefamous magic shows by his name sake,David Copperfield. He showed a video ofBrown's Syndrome "fixed" by exaggeratedforced ductions and no surgery. DavidGuyton, MD was right there to see hisforced duction test being used as a cure forBrown's Syndrome. Magic exemplified!This was followed by a video of "magician'sforcep", where the contralateral eye moveswhen the ipsilateral eye is ducted undergeneral anesthesia. This was first reportedby Tamura in 1986 [Tamura O, Mitsui Y.The magician's forceps phenomenon in

exotropia under general anaesthesia. Br JOphthalmol 1986; 70:549-552].

The audience was just aboutrecovered from the entertaining magic showwhen they were challenged by yet anothervery intriguing case presentation by KenWright, MD. This was a 4 year old childwho had undergone a superior obliquetendon expander procedure for Brown'sSyndrome elsewhere, and developed anovercorrection and consecutive head tilt. Dr.Wright was consulted. He stated that if thereis an overcorrection after superior obliquetendon expander, with inferior obliqueoveraction, inferior oblique recession withpartial anteriorization is the procedure ofchoice. In this case, because of the largehead tilt, and minimal inferior obliqueoveraction, Dr. Wright used an ipsilateralHarada Ito procedure. This worked well asit addressed the extorsion that was drivingthe head tilt.

David Guyton, MD concluded thissession with a case of unusual hyper-deviation in thyroid ophthalmopathy. Ayoung female with thyro id myopathypresented with vertical diplopia due to aright hypertropia with right inferior obliqueoveraction and right extorsion. Forcedduction testing showed a normal left inferiorrectus (not tight) and a tight right inferioroblique. No enlarged extraocular muscleswere seen on scans. She had a right inferioroblique recession; however, 2 weeks laterthe symptoms returned and forced ductionsshowed again diffuse tightness of the rightinferior oblique. This was corrected with aright inferior oblique denervation andextirpation.

Ken Wright, MD shared with theaudience a similar case he had seen manyyears ago, where he biopsied the inferioroblique and it turned out to be fibrotic. Heconcurred with Guyton's findings that themuscle does not necessarily have to beenlarged; it can be contracted due tofibrosis.

Scientific Session 2

Binocular Vision & Strabology Report of the 2nd Pediatric Ophthalmology and Strabismus Day First Quarter of 2007Stra bism us Qu arte rly© An Extravaganza in Las Vegas, USA, Di rected by K. W r ight, MD Volume 22 (No.1):57-63

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Malcolm Ing, MD, surfing championfrom Hawaii, USA, presented a retro-spective series of 41 patients and aprospective series of 44 patients withcongenital esotropia wherein the esotropiadeviation showed a progressive increaseand thus required an increase in the surgicaldosage when compared to the plan made amonth or two prior to surgery [Ing MR.Progressive increase in the angle ofdeviation in congenital esotropia. Trans AmOphthalmol Soc 1994; 90:117-125; IngMR, Norcia A, Stager D et al. A pro-spective study of alternating occlusionbefore surgical alignment for infantileesotropia: One year postoperative motorresults. J AAPOS 2006; 10:49-53]. Dr. Ingstated that the late Dr. Marshall Parks, 3months before his demise, had commentedthat this study showed that the medialrectus muscles get progressively tighterwith time and this gives us motor reasons tojustify early surgery. This was in line withDr. Wright's prediction several years agofor the need of early surgery for infantileesotropia [Wright KW, Edelman PM,McVey JH, Terry A, Lin M. High grades tereo acui ty a f te r ea r ly su rge ry fo rcongenital esotropia. Arch Ophthalmol1994;l 112:913-919].

Joseph Demer, MD, PhD, from LosAngeles, USA, gave a passionate talk ontechniques in pulley surgery. His talk wasillustrated with excellent MRI imagesshowing the three types of pulley pathologythat cause incomitant strabism us: (a)Heterotopy where pulleys are misplaced;e.g., inferior heterotopy of the lateral rectus(LR) pulley is associated with a V pattern,alternating hypertropia when bilateral.While early cases were operated by superiortransposition of the LR insertion andposterior fixation to the sclera of thesuperior border of the LR tendon, a moreeffective operation may be imbrication ortucking of the ligament that joins the LRand superior rectus pulleys. (b) Instability,the gaze related shift of orbital pulleys;similar approaches as described above wereadvised for LR pulley instability. (c)Infer ior rectus (IR) pulley hindrancetypically arises from inferior orbital traumaor lower eyelid surgery. Hindrance to IRpulley may be treated by surgical release

via transconjunctival inferior orbitotomy,depot steroid injection and inferior tractionsuturing.

James L. Mims III, MD, from Texas,USA, presented a very interesting studytitled "The exoshift under anesthesia at thefirst and second surgeries reveals thatfus ion reduces medial rectus hyper-innervation in infantile esotropia". Thestudy addressed the question: Is medialrec tus (MR) hyper innerva tion amonginfantile esotropes reduced to normal aftersuccessful surgery to align the eyes? Mimsand Aaron M. Miller, MBA, MD tabulatedmeasurements of the angle under anesthesiamade from 1988 to 1998 using a sterileprism bar and the surgeon's fiberopticheadlight. The difference between thepreop' strabismus angle in the awake patientand the angle u nder anes thesia, the"exoshift under anesthesia", appears toparallel the level of innervation of themedial rectus muscles. From a large seriesof such measurements, Mims & Millerconcluded that the MR hyperinnervationamong 17 infantile esotropes was down-modulated by 2/3 after successful hori-zontal alignment, with normal indicated bya series of 21 patients undergoing surgeryfor superior oblique palsy, with someresidual hyperinnervation to compensate forlateral rectus contracture. Among 27patients with residual or recurrent esotropiaaveraging half the original angle pre-operatively, previous MR recessions did notresult in any reduction in the initial MRhyperinnervation of infantile esotropia .Also, they found that the small residualhyperinnervation required to compensatefor contracture of the antagonist LR tomaintain orthotropia reverted to normal in16 consecutive exotropes.

Miho Sato, MD, from Japan, spokeon Class III and Class IV tendon anomaliesof congenital superior oblique (SO) palsy.She highlighted that imaging studies wereessential for detecting severe tendonanomaly and Class III and Class IV weredifficult to distinguish without explorationof Tenon's capsule.

Irene Ludwig, MD commented thatshe had moved to doing SO advancement

Binocular Vision & Strabology Report of the 2nd Pediatric Ophthalmology and Strabismus Day First Quarter of 2007Stra bism us Qu arte rly© An Extravaganza in Las Vegas, USA, Di rected by K. W r ight, MD Volume 22 (No.1):57-63

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instead of tucks not too long ago. She said"I looked at the tendon in almost everycase. I think it's even more common thanyou think - the more minor anomalousinsertions are very common and I see a lotof it in V-pattern esotropia in kids,especially an arrow pattern. So I think youare right but I think these tendon anomaliesare more common than you think."

Dr. Wright shared his views on 2patients who had traumatic avulsion of theSO tendon and presented with SO palsy.Guess what kind of strabismus they had?Almost no vertical deviation in the primaryposition. They had significant extorsionworse in downgaze and to the opposite side.The vertical deviations were almost notnoticeable. If by removing the SO tendon,in an otherwise normal patient, one getsonly a small vertical deviation, how do youexplain the large vertical deviations seenwith congenital superior oblique palsy,based solely on the SO anomaly? It isobviously more than the weak superioroblique and the larger vertical must be dueto inferio r obliqu e ove raction an d/orsecondary superior rectus contracture. Dr.Wright emphasized that it's just not a palsy.

Scientific Session 3David Guyton, MD gave a succinct

p r e s e n t a t io n o n " I n v e r t e d B r o w n 'sSyndrome" due to a tight or inelasticinferior oblique muscle. Twelve patientspresented with at least 8 prism diopters ofhypertropia in gaze down and in, withsuper ior obliqu e und eract io n wi thoutipsilateral inferior oblique o veract ion.Forced ductions showed that 9 out of 12patients had tight inferior oblique. Nonehad a lax superior oblique tendon onexaggerated forced ductions. Etiology: 3had surgery for Brown's Syndrome, 4 hadorbital floor fracture repair and 5 had onlyapparent superior oblique paresis. Four ofthe 12 underwent contralateral inferiorrectus recession and postoperatively all 4h a d r ecurren ce of supe r ior ob l iq u eoveraction over an average followup of 11months. Eight of the 12 had inferior obliqueweakening and had good results. Inferioroblique weakening yields better results thancontralateral inferior rectus muscle reces-sion, even though there is no significant

inferior oblique muscle overaction preop-eratively.

Ken Wright, MD presented a paperon the use of a novel grooved hook forrectus recession under topical anesthesiaand for inferior oblique surgery. Thegrooved hook facilitates exposure of rectusmuscles and in ferior o blique muscleallowing safe suturing of the muscledirectly over the hook for recession surgery.The groove in the hook guides the needlepass, protecting the underlying sclera fromi n a d v e r te n t n e e d l e p u n c t u r e, w h i l eproviding consistent suture placement withrespect to the scleral insertion. It is alsouseful for suturing inferior oblique musclesas it protects the sclera in the area of themacula. Over 200 muscles were operatedupon using this hook. The grooved hook isespecially helpful for suturing of tightrectus muscles and for topical anesthesiastrabismus surgery wherein the patient willexperience pain when the muscle is liftedoff the sclera using standard strabismushooks (Figures A-D, next page). (Dr.Wright has a US patent and a financialagreement with Titan Surgical Company.)He stated that though he has a financialinterest in the hook, he can still not quit hisday job!

Dr. Wright's talk also had videos ofsurgery showing the use of the Wright hookfor inferior oblique surgery. This has beenrecently published by Springer in the 3rdedition of the "Color Atlas of StrabismusSurgery, Strategies and Techniques" byKenneth Wright. This comes with a DVDof 15 strabismus surgical procedures.

Following this talk, Mike Brodsky,MD from Arkansas, USA, presented apaper co-authored with Dr. Wright on threechildren with infantile esotropia and headoscillations where surgical treatment of theinfantile esotropia produced simultaneousresolution of the head shaking/nodding. A

Binocular Vision & Strabology Report of the 2nd Pediatric Ophthalmology and Strabismus Day First Quarter of 2007Stra bism us Qu arte rly© An Extravaganza in Las Vegas, USA, Di rected by K. W r ight, MD Volume 22 (No.1):57-63

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video was shown of Dr. Wright's patientwith the head nodding preoperatively andits resolution postoperatively. Dr. Wrightwas using a pen as a fixation target to elicitthe eye movements. A timely commentfrom Ed Wilson, MD who asked if thefixation target used by Dr. Wright was alsospecial and called "Wright's pen" and hewas right; it was indeed a "Wright Founda-tion pen". The audience roared w ithlaughter.

Strabismus Round Table - BTony Murray, MD, from South

Africa, shared with us a rare case oftraumatic strabismus. A young man wasstabbed in the forehead resulting in alaceration involving the right upper lid. Theincision went through conjunctiva andTenon's capsule, but spared the globe andthe sinuses. The patien t had lim itedadduction in the right eye. CT scan showedthat he had a slipped medial rectus muscle.It turned out that, although the anterior partof the muscle sheath and tendon was cut,the posterior part of the sheath was in tact,and the intermuscular membrane wasspared. It was therefore relatively easy tofind the slipped muscle and reattach this tothe original insertion. The patient regainedfull motility. However, as he had anunsightly notch on the upper eyelid margin,he returned two weeks later for furtherrevision, at which time he had sustained afurther canalicular laceration on the otherside!

Ken Wright, MD and Malcolm Ing,MD each presented a case of overcorrectionfollowing inferior oblique recession andcontralateral inferior rectus (IR) recessionfor congenital superior oblique palsy. Ing'scase was caused by a stretched scar inferiorrectus with the IR slipping back. Wright'scase was an over-anteriorized IO with theIO found anterior to the IR insertion.Clinically, the slipped IR has a greaterh y p e r i n do w ng a z e a n d t h e o v er-anteriorized IO causes a greater hyper inupgaze associated with limited elevation oft h e e y e w i th t h e i n f e r io r o b l i q ueanteriorization. Wright noted that it isimportant to avoid anteriorizing the IOanterior to the inferior rectus insertion andto keep the posterior fibers of the IO severalmillimeters posterior to the anterior fibers

thus avoiding the "J" deformity [Guemes A,Wright KW. Effect of graded anterior trans-position of the inferior oblique muscle onversions and vertical deviation in primaryposition. J AAPOS 1998; 201-206].

An entire day of intense academicexchange concluded with a wine reception.

The Third Pediatric Ophthalmologyand Strabismus Day, again hosted by theWright Foundation and Alcon LaboratoriesInc., will be held on November 10, 2007 inNew Orleans, USA, at the Ochsner In-stitute, immediately preceding the nextannual American Academ y of Ophth-almolgy meeting. For inquiries, pleasecontact: Gabby at [email protected] or Sonal at [email protected]

The papers and discussion at thismeeting were audiotaped and are availablefrom Audio-Digest Foundation. Contact:Ms. Marilyn Lowry, Conference Coordi-natorAudio-Digest Foundation1577 E Chevy Chase DriveGlendale, CA 91206Fax: [email protected]

DISCLAIMER: While the reporter hasendeavored to be as accurate as possible inreporting the presentations at this meeting, thereader is strongly advised to confirm anyinformation in this report, for sure, before actingupon it or applying it to patients!