brief reports fev_.2001pdf

Brief Reports

BILATERAL PREPAPILLARY LOOPS WITHUNILATERAL BRANCH RETINAL ARTERYOCCLUSION FOLLOWING THROMBUS ATTHE LOOP APEX

KAMIAR MIRESKANDARI, FRCSED, FRCOPHTH,CHRISTOPHER BENTLEY, FRCOPHTH,WAGIH A. ACLIMANDOS, FRCS, FRCOPHTH

From the Department of Ophthalmology, King’s Col-lege Hospital, London, England.

Liebrich first described a prepapillary arterial loopin 1871. This is a congenital vascular anomaly thoughtto originate from a main branch of the central retinalartery.1,2 These loops are usually unilateral and morecommon than venous loops. Most are asymptomaticbut rare cases of retinal artery obstruction have beenseen, most commonly affecting the inferior retina. Wereport a case of unilateral branch artery occlusion in apatient with bilateral loops demonstrating a thrombusat its apex with a follow-up period of 18 months.

Case Report

A 24-year-old African man presented with sudden loss of visionin his right eye while reading in bed. Shortly after, the inferior fieldof vision started to return and became normal but the superiorvisual field loss remained. There were no other symptoms orrelevant medical or ocular history. On examination the visualacuity was 6/6 in both eyes. There was a mild relative afferentpupillary defect and a marked superior altitudinal field defect in theright eye. Examination of the right fundus revealed a twistedprepapillary loop (PPL) and a pale and edematous inferior retina(Figure 1A). The left eye showed a similar but smaller loop.Laboratory tests including hemoglobin electrophoresis were nor-mal. The fluorescein angiogram confirmed the inferior hemisphericarterial occlusion and the PPL did not fill at any stage (Figure 1B).The vascular pattern at the disk was unusual with more than onecilioretinal artery present.

Three months later, the PPL was empty of blood and a smallthrombus could be seen at the apex of the loop (Figure 2A). Theinferior retinal arteries were attenuated and the pallor had resolved.Eighteen months later, the blood supply to the inferior retina hadimproved. The fluorescein angiogram demonstrated slow filling ofthe inferior retinal arteries possibly via cilioretinal collaterals (Fig-ure 2B) whereas the PPL remained occluded and gliosed.

Discussion

There has been some debate over the origin of PPL,principally concerning whether they are derived fromthe hyaloid or retinal arterial system. Mann1 suggestedthat the loops originate at about the 100 mm embry-onic stage at the time when retinal vascularizationbegins. It is postulated that the retinal artery firstextends forward within Bergmeister’s papilla (glialtissue anterior to the optic nerve) instead of turning 90degrees to grow radially onto the retina. When theBergmeister’s papilla atrophies, the vessel loop is leftprotruding into the vitreous cavity. Two anatomicstudies have supported the view of retinal arterialconnection.2,3 There have been 10 cases of retinalarterial occlusion associated with unilateral loops butnone with bilateral loops or where the thrombus wasdemonstrated.4–7

Although generally considered to be benign, PPLare associated with arterial occlusions, amaurosis fu-gax, vitreous hemorrhage, and hyphema. As mostloops are asymptomatic and therefore remain eitherunseen or merely documented as a chance finding, thetrue incidence of these rare complications remainsunknown. In this case as with most others reported,there was an abnormal peripapillary vascular patternwith unusual cilioretinal circulation. Furthermore, theinferior retinal arteries were those affected, the patientwas young, and there were no associated systemicfindings.

The mechanisms of occlusion of the PPL are notclear. Some authors have postulated a mechanicaleffect secondary to the spiral makeup of the loopleading to increased turbulence or torsion especially inassociation with posterior vitreous detachment. Thesize of the loop is thought to be important as well as

Presented at the Royal Society of Medicine; London; October 6,1999.

The authors have no proprietary interests.Reprint requests: Kamiar Mireskandari, FRCSEd, FRCOphth,

Flat 2, 109 Sutherland Avenue, Maida Vale, London W9 2QH,England.

RETINA,™ The Journal of Retinal and Vitreous Diseases,encourages authors to submitBrief Reports describing unusual findings, newtechniques, and new instruments. Material submitted for consideration in this section of the journal is done so with the assumption that thedata provided do not duplicate previously published material and that the material has not been submitted for consideration elsewhere. Eachauthor must sign a disclosure to this effect (see Instructions to Authors for complete wording of transfer letter). Brief Reports submitted forthis section of the journal may be subjected to the standard review process that is applied to other material submitted toRETINA . BriefReports should follow the requirements listed in the Instructions to Authors, with the following caveats: Brief Reports should not exceed 4pages in length; no more than 5 references should be cited; and each Brief Report should include no more than 4 figures.

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any focal narrowing that may trap chance emboli.Careful observation and monitoring of patients withthis rare complication might reveal more specific pre-disposing factors.

References1. Mann I. Developmental Abnormalities of the Eye, 2nd Ed.

Philadelphia: JB Lippincott, 1957;133–136.2. Goldstein I, Wexler D. The preretinal artery. An anatomical

study. Arch Ophthalmol 1929;11:324–334.3. Shakin EP, Shields JA, Augsburger JJ, Brown GC. Clinico-

pathological correlation of a pre-papillary vascular loop. Retina1988;8:55–58.

4. Harcourt R, Locket N. Occlusion of a pre-retinal arterial loop.Br J Ophthalmol 1967;51:562–565.

5. Khoda N, Nakan Ishi Y. A case of pre-papillary arterial loopswith retinal artery obstruction. Jpn J Clin Ophthalmol 1977;31:744–745.

6. Brown GC, Margaral LE, Augsburger JJ, Shields JA. Pre-retinalarterial loops and retinal arterial occlusion. Am J Ophthalmol1979;87:646–651.

7. Limaye SR, Tang RA, Pilkerton AR. Cilio-retinal circulationand branch arterial occlusion associated with pre-retinal arterialloops. Am J Ophthalmol 1980;89:834–839.

Fig. 2. A, Magnified view ofempty loop with thrombus atthe apex.B, Angiogram 18months later shows delayedperfusion inferiorly.

Fig. 1. A, Right inferiorhemispheric retinal artery oc-clusion and prepapillary loop.B, Acute fluorescein angio-gram shows arterial nonperfu-sion and empty prepapillaryloop.

67BRIEF REPORTS

PURTSCHER’S RETINOPATHYSECONDARY TO AIRBAG INJURY

GAURAV K. SHAH, MD,*ROBERT PENNE, MD,†M. GILBERT GRAND, MD*

From *Barnes Retina Institute and the Department ofOphthalmology and Visual Sciences, Washington Uni-versity School of Medicine, St. Louis, Missouri; and†Wills Eye Hospital, Philadelphia, Pennsylvania.

Airbags have become a popular means of reducinginjury and death in motor vehicle accidents. A recentNational Highway and Traffic Safety Administrationstudy estimated that airbags had saved the lives ofapproximately 3500 Americans as of September1998.1 Airbags cushion occupants from the rigid com-ponents in a vehicle and need to be fully inflatedbefore an occupant moves forward to provide the mostadequate protection. Unbelted passengers move for-ward further than belted passengers, which increasesthe risk of striking an expanding bag that is propelledout from its storage compartment at typically morethan 100 miles per hour. Theoretically, unrestrainedpassengers may strike the airbag not only with theirhead but also with their thoracic region due to theabsence of a shoulder harness.

Airbags have been known to cause a multitude ofocular injuries, including corneal abrasions, alkaliburns, traumatic cataracts, retinal and vitreous hemor-rhages, retinal tear and detachment, macular holes, andchoroidal ruptures.2,3 We present a case of Purtscher’sretinopathy following deployment of an airbag.

Case Report

A 33-year-old man presented with decreased vision in both eyesafter being involved in a motor vehicle accident. He was anunrestrained driver involved in an accident that occurred at lessthan 20 miles per hour. Although he was not wearing a seat belt, hiscar was equipped with an airbag, which inflated at the time of theaccident. His visual acuity was 20/30 in the right eye and countfingers in the left eye. He had a 31 afferent pupillary defect in theleft eye. Intraocular pressures were within normal limits. Theanterior segment examination was remarkable for 11 cell and flarein the left eye; the right eye was quiet. The posterior segmentexamination of both eyes revealed multiple areas of yellow–whitepatches at the inner retina level along with superficial intraretinalhemorrhages (Figure 1, A and B). The peripapillary changes weremore pronounced in the left compared to the right eye. The left eyealso revealed several blot hemorrhages in the posterior pole. Afluorescein angiogram showed early blockage of the choroidal

fluorescence in the area of the yellow–white patches, whereas thelate frames revealed hyperfluorescence (Figure 2, A and B). Alongwith loss of vision, the patient had periorbital ecchymoses, but nofractures or systemic injuries. No chest contusion or trauma weresuspected owing to lack of subjective chest pain or radiologicevidence of fractures of ribs or sternum. Given the constellation ofclinical findings, he was diagnosed with Purtscher’s retinopathywith a component of traumatic optic neuropathy.

The patient’s follow-up after the injury was sporadic, but hisvision did not improve in the left eye and remained at count fingers3 months after the injury. The right eye stayed at 20/30.

Discussion

Purtscher’s retinopathy was first described byPurtscher in 1912, with findings of white retinalpatches and superficial retinal hemorrhages in patientswith head trauma. Since the original description, otherconditions associated with Purtscher’s have been re-ported, including acute pancreatitis; fat, air, or amni-otic embolization; lymphoproliferative disorders;chest compression; bone marrow transplantation; andmost recently pancreatic adenocarcinoma.4 We areunaware of any previous report of Purtscher’s retinop-athy resulting from airbag injuries.

Either direct blunt trauma to the face or a compres-sive effect in the thoracic region may have led to thedevelopment of a Purtscher-type retinopathy in ourpatient. The pathophysiology of Purtscher-like reti-nopathy is uncertain. An increase in thoracic pressuremay lead to a reflux in the venous system. Subsequentendothelial damage can cause incompetence of themicrovascular system, resulting in occlusion and isch-emia. Complement derived C5a has also been associ-ated with the initiation of intravascular aggregation insome of the conditions associated with Purtscher-likeretinopathy.5 In clinicopathologic studies, occludedretinal arterioles and choroidal vessels along withdamage to the photoreceptors have been described.

In our patient, the facial contusion may have led tothe Purtscher’s and the traumatic optic neuropathy.The tractional forces at the time of injury may havedisrupted the posterior ciliary arteries, causing a sec-ondary ischemic optic neuropathy from the trauma.There may also have been contusion necrosis, com-pression, axonal disruption, and ischemia, all account-ing for the traumatic optic neuropathy associated withthe airbag injury. The same mechanism responsiblefor traumatic optic neuropathy also leads to aPurtscher-type response, with retinal edema and hem-orrhage in the posterior pole. In this case there mayhave been a combined mechanism for the Purtscher’s,with both direct trauma to the face and a compressiveeffect in the thoracic region. Owing to lack of injury tothe thoracic region, direct facial trauma may be the

Reprint requests: Gaurav K. Shah, MD, Barnes Retina Institute,One Barnes Hospital Plaza, Suite 17413, St. Louis, MO 63110;e-mail: [email protected]

68 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES ● 2001 ● VOLUME 21 ● NUMBER 1

most likely cause for both the Purtscher’s and theoptic neuropathy.

This report describes a case of Purtscher-like reti-nopathy in association with an airbag-related injury inan unrestrained passenger. The mechanism, althoughunknown, is most likely due to a compressive-typeinjury. Despite this injury, our patient most likelyavoided serious head injury due to the protective ef-fects of the airbag. It is conceivable that by using hisseat belt he may have been able to avoid his retinalinjuries. Purtscher’s retinopathy should be added tothe list of complications from airbag-related injuries.The future development of more sophisticated airbagscan only enhance the safety features of the system anddecrease the risk of secondary injuries due to theairbags themselves.

References1. Insurance Institute for Highway Safety. Airbags [online].

Available at: http://www.highwaysafety.org/airbags/airbag.htm.Accessed March 20, 1999.

2. Kuhn F, Morris R, Witherspoon CD. Eye injuries and theairbag. Curr Opin Ophthalmol 1995;111:38–44.

3. Stein JD, Jaeger EA, Jeffers JB. Airbags and ocular injuries.Trans Am Ophthalmol Soc 1999;97:59–82.

4. Tabandeh H, Rosenfeld PJ, Alexandrakis G, et al. Purtscher-

like retinopathy associated with pancreatic adenocarcinoma.Am J Ophthalmol 1999;128:650–655.

5. Snady JL, Morse PH. Retinopathy associated with acute pan-creatitis. Am J Ophthalmol 1985;100:246–251.

SURGICAL REMOVAL OF A LASER-INDUCED CHOROIDAL NEOVASCULARMEMBRANE

ANDRÉS KYCHENTHAL, MD,*ALEJANDRO SIEBERT, MD,*PAOLA DORTA, MD,*BILL AYLWARD, MD†

From *Clínica Alemana, Santiago, Chile; and †Moor-fields Eye Hospital, London, United Kingdom.

Choroidal neovascular membranes (CNVM) can besecondary to numerous causes that allow neovascularingrowth from the choroid through a defect in Bruch’s

Reprint requests: Andrés Kychenthal, MD, Clínica Alemana deSantiago, Vitacura 5951, Santiago, Chile; e-mail: [email protected]

Fig. 2. A, Early phase of thefluorescein angiogram of theleft eye reveals blockage ofthe choroidal circulation sec-ondary to yellow–white patchesin the peripapillary region.B,Late frame of the fluoresceinangiogram reveals peripapil-lary hyperfluorescence withstaining of the optic nerve.

Fig. 1. A, Color photographof the right eye shows super-ficial intraretinal hemorrhagesalong with yellow–whitepatches in the peripapillaryregion.B, Extensive peripap-illary yellow–white patchesare noted around the opticnerve. Note multiple retinalhemorrhages in the posteriorpole of the left eye.

69BRIEF REPORTS

membrane. Iatrogenic CNVM after laser photocoagu-lation for different conditions have been reported.1

The development of an iatrogenic CNVM after laserphotocoagulation in diabetic patients represents anuncommon but serious complication.2,3 We present acase of subfoveal iatrogenic CNVM treated by surgi-cal removal with a good visual outcome.

Case Report

In April 1997, a 34-year-old woman with a 20-year history ofinsulin-dependent diabetes presented with blurred vision in botheyes for 2 days. Visual acuity was 20/30 in both eyes. Clinicallysignificant macular edema was present in the right eye. Clinicallysignificant macular edema and new vessels located at the disk andalong the superior arcade were present in the left eye. Four dayslater the patient underwent laser photocoagulation in both eyes.Focal laser of the right eye was performed with a 532-nm laser(Ophthalas 532, Alcon, Fort Worth, TX), 11 applications to theposterior pole (100mm spot size, 0.1 second duration, 70 to 100mW power).

One month after photocoagulation vision in the right eye was20/100. Two months later vision dropped to 20/200 and fundusexamination showed a CNVM with foveal involvement. Fivemonths after laser treatment vision was 20/400 and fluoresceinangiography showed a CNVM with a “classic” angiographic pat-tern. In April 1999, 2 years after focal laser to the right eye, visionwas still 20/400 with significant distortion. Fundus examinationrevealed clinical and angiographic signs of an active CNVM in-volving the fovea (Figure 1).

In May 1999, the patient underwent pars plana vitrectomy andremoval of the CNVM. At the first month follow-up vision im-proved to 20/80. Five months after surgery vision was 20/70 and noevidence of recurrence was noted during the follow-up period(Figure 2).

Discussion

Surgical removal of subfoveal CNVM is now welldescribed. The difference in visual outcome after sur-gery for subfoveal CNVM in different clinical condi-tions was explained by Gass.4 With the fundus appear-ance and the histologic pattern, Gass suggested twodistinct types of choroidal neovascular growth. InType 1 CNVM, such as in age-related macular degen-eration, diffuse changes in Bruch’s membrane areassociated with multiple ingrowth sites and theCNVM develops beneath the retinal pigment epithe-lium (RPE). In Type 2 CNVM, such as seen in mul-tifocal choroiditis and presumed ocular histoplasmosissyndrome, there tends to be a single ingrowth site thatproliferates anterior to the RPE in the subsensoryretinal space. When Type 2 membranes are removed,preservation of native RPE could lead to good visualfunction. We report a case of a surgically treatediatrogenic subfoveal CNVM secondary to laser pho-

Fig. 1. A, Preoperative colorfundus photograph shows la-ser photocoagulation scarsand the subfoveal laser-in-duced choroidal neovascularmembrane. B, Preoperativefluorescein angiogram showsfluorescein leakage from thesubfoveal choroidal neovas-cular membrane.

Fig. 2. A, Color funduspho-tograph 3 months after surgicalremoval shows no clinical singsof the choroidal neovascularmembranes. Some pigmentaryatrophy in the macular areais present.B, Postoperative fluo-rescein angiogram shows com-plete excision of the choroidalneovascular membrane.


tocoagulation in a diabetic patient with macularedema.

Current surgical techniques allow CNVM removalwith visual stabilization or improvement in a numberof clinical conditions. Our patient improved in Snellenvisual acuity from 20/400 to 20/80. This patient alsoobserved a great decrease in distortion. These goodresults could be explained by the localized action oflaser, which is more compatible with the formation ofa Type 2 CNVM and thus preservation of native RPEafter surgery.

Timing of the surgical removal of CNVM is un-clear. In this case we report good visual functionobtained after pars plana vitrectomy and CNVM re-moval for a iatrogenic laser-induced CNVM in a di-abetic patient, 2 years after the CNVM developed.

References1. Ching JC, Urban LL, Nelson NC, Fratkin JD. Surgical removal

of iatrogenic choroidal neovascular membranes. Ophthalmol-ogy 1998;105:1606–1611.

2. Chandra SR, Bresnick GH, Davis MD. Choroidovitreal neo-vascular ingrowth after photocoagulation for proliferative di-abetic retinopathy. Arch Ophthalmol 1980;98:1593–1599.

3. Wallow I, Johns K, Barry P, et al. Chorioretinal and chorio-vitreal neovascularization after photocoagulation for prolifer-ative diabetic retinopathy. A clinicopathologic correlation.Ophthalmology 1985;92:523–532.

4. Gass JD. Biomicroscopic and histopathologic considerationsregarding the feasibility of surgical excision of subfoveal neo-vascular membranes. Am J Ophthalmol 1994;118:285–298.

VISUAL RECOVERY FROM MACULARPHOTOTOXIC INJURY FOLLOWINGCATARACT SURGERY

MICHAEL S. LEE, MD,STEPHEN E. ORLIN, MD,ALEXANDER J. BRUCKER, MD

From the Scheie Eye Institute, Department of Oph-thalmology, University of Pennsylvania School ofMedicine, Philadelphia.

McDonald and Irvine first described retinal phototox-icity from an operating microscope in 1983 followinguncomplicated cataract extraction with posterior

chamber intraocular lens implantation.1 Since then,these lesions have been described in cases with ante-rior chamber lens placement and in cases without anylens placement.2,3 Of the reported cases of phototox-icity following cataract extraction, almost all had ex-trafoveal lesions with mild to moderate loss of visualacuity (VA) followed by spontaneous recovery withina few months postoperatively.

We describe a patient who had profound visual losssecondary to macular phototoxicity following cataractextraction. Visual improvement did not occur until 8months postoperatively.

Case Report

A 63-year-old man was struck in the left eye by a golf ball andwas treated medically for a traumatic hyphema and uncontrolledintraocular pressure (IOP). Three months later he was referred formanagement of progressive shallowing of the anterior chamber, atraumatic cataract, and glaucoma.

Examination revealed VA of 20/20 in the right eye and 20/70 inthe left, improving with pinhole to 20/40. The results of anteriorsegment and funduscopic examination of the right eye were nor-mal. The left pupil was 9 mm and minimally reactive with multiplesphincter tears. There was no afferent pupillary defect. Slit-lampexamination showed a traumatic cataract with mild phacodonesisand a shallow anterior chamber. With compression gonioscopy,anterior trabecular meshwork was visible inferiorly with scatteredperipheral anterior synechiae. The IOP was marginally controlledat 28 mmHg on latanoprost 0.005%, dorzolamide 2%/timolol0.5%, and brimonidine 0.2%. Fundus examination showed pigmentcells in the vitreous, but healthy disk, macula, and vessels. B-scanultrasonography confirmed the forward displacement of the normalthickness crystalline lens.

Because of the progressive forward displacement of the lens andmarginal IOP control, it was decided to remove the traumaticcataract via an anterior approach. The patient was taken to theoperating room for planned phacoemulsification using the ZeissOPMI (West Germany) operating microscope. During the capsu-lorhexis, the lens was noted to spin freely and the case wasconverted to an intracapsular procedure. An anterior vitrectomywas performed. An attempt to sew in a posterior chamber intraoc-ular lens was aborted because of poor centration within the dilated,traumatized pupil.

On the first postoperative day, the patient noted a central sco-toma with best-corrected vision of hand motions (HM). There wasmild corneal edema and a moderate amount of inflammation in theanterior chamber. The IOP was normal, and there was no afferentpupil defect. Dilated fundus examination revealed a 4–disk diam-eter elliptical area of retinal whitening in the macula involving thefovea. The lesion was highly suggestive of a macular phototoxicityburn (Figures 1 and 2).

Best-corrected VA improved to 20/400 at 10 weeks and re-mained at that level until 6 1/2 months, where it improved to20/200 with an aphakic contact lens. At 8 months follow up, thevision had improved to 20/40 with manifest refraction and 20/25with an aphakic contact lens. The macular whitening graduallyresolved, leaving retinal pigment epithelial changes with areas ofatrophy and hyperplasia (Figure 3).

The authors have no proprietary interest in the outcome of thisreport.

Reprint requests: Alexander J. Brucker, MD, Scheie Eye Insti-tute, 51 North 39th Street, Philadelphia, PA 19104; e-mail:[email protected]

71BRIEF REPORTS

Discussion

Retinal phototoxicity following anterior segmentsurgery does not involve the fovea in most cases. Twomechanisms for foveal sparing have been proposed. Ithas been postulated that there is a protective effect ofhigher levels of xanthophyll pigment in the fovea,which absorbs the blue light most responsible forphototoxic injury. Additionally, light from operatingmicroscopes is not coaxial with the visual axis in mostcases of cataract surgery, thus avoiding the fovea.1–5

However, we found four cases of phototoxicityinvolving the fovea following cataract extraction de-scribed in the literature. Reported VA in these patientsranged from 20/100 to 20/200 postoperatively withvisual recovery to better than 20/30 in three over thecourse of 3 months; the fourth patient remained at20/200.2,4,5

Postel et al4 reported four cases of foveal phototox-icity after vitreoretinal surgery. The macula was sub-jected to intense light from endoilluminators withoutthe protective effect of the phakic lens for longerperiods of time. These patients’ VA ranged from 20/400 to HM postoperatively. Two of these patientsexperienced only minimal improvement and two hadworsening of their VA.

Initial postoperative VA in cases of macular pho-totoxicity involving the fovea has been reported to beonly moderately affected following cataract surgery(20/100–20/200). Good recovery occurred within afew months in all cases. Foveal injury after vitrec-tomy, however, is typically more profound with pooroutcome. As in the current case, despite profoundvisual loss (HM), excellent visual recovery can occuras late as 8 months postoperatively, which may beuseful in patient counseling.

Fig. 2. Early (A) and late (B)frames of the fluorescein an-giogram of the lesion de-picted in Figure 1.

Fig. 1. Appearance of the phototoxic lesion 1 week postoperatively.Blurred fundus appearance is secondary to corneal edema. Visualacuity is hand movements.

Fig. 3. Lesion from Figures 1 and 2, 8 months postoperatively. Visualacuity is 20/25 with aphakic contact lens.


References1. McDonald HR, Irvine AR. Light-induced maculopathy from

the operating microscope in extracapsular cataract extractionand intraocular lens implantation. Ophthalmology 1983;90:945–951.

2. Boldrey EE, Ho BT, Griffith RD. Retinal burns occurring atcataract extraction. Ophthalmology 1984;91:1297–1302.

3. Lindquist TD, Grutzmacher RD, Gofman JD. Light-inducedmaculopathy: potential for recovery. Arch Ophthalmol 1986;104:1641–1647.

4. Postel EA, Pulido JS, Byrnes GA, et al. Long-term follow-upof iatrogenic phototoxicity. Arch Ophthalmol 1998;116:753–757.

5. Ross WH. Light-induced maculopathy. Am J Ophthalmol1984;98:488–498.

SECTOR RETINITIS PIGMENTOSA WITHBITEMPORAL VISUAL FIELD DEFECTSAND MACULAR HOLE

DAVID A. SAPERSTEIN, MD

From Emory Eye Center, Emory University School ofMedicine, Atlanta, Georgia.

This case report describes a patient who presentedwith sector retinitis pigmentosa with bitemporal visualfield defects complicated by a macular hole.

Case Report

A 63-year-old woman sought a second opinion concerning grad-ual decreased central vision in the left eye diagnosed as cystoidmacular edema (CME). She has a history of retinitis pigmentosa(RP). She reported that her mother had very poor vision as a resultof RP. Her only other visual complaint was nyctalopia. In 1985 herGoldmann visual fields (GVF) were full (using V4e–I4e targets). InAugust 1997, she noted decreased vision. At that time she was seenby another physician and her visual acuity (VA) was 20/20 in theright eye and 20/80 in the left. Dilated fundus examination revealedRP-like changes and an abnormality in the macula of the left eyethat was diagnosed as CME. Goldmann visual field examinationrevealed bitemporal scotomata.

This unexpected visual field finding closely resembled that pro-duced by a central chiasmal lesion. Magnetic resonance imaging ofthe brain revealed no pathology. The CME was thought to berelated to RP and the patient was treated with oral acetazolamide,retroseptal steroids, and topical 1% prednisolone acetate drops.Over several months her VA dropped to 20/200 in the left eye.

In January 1998, the patient was examined in our clinic. Her VAwas 20/20 in the right eye and 20/200 in the left eye. Intraocularpressures were 13 mmHg in the right eye and 11 mmHg in the left.The external examination was unremarkable. The anterior segmentshowed mild nuclear sclerotic cataracts. The vitreous was clear inboth eyes. The cup-to-disk ratio was 0.4 in both eyes. Funduscopyrevealed that arteries nasal to the foveae in both fundi were atten-uated. There were typical “bone spicule” like pigmented lesionsnasal to the foveae in both eyes (Figure 1, A and B). There were nopigment abnormalities temporal to the foveae in either eye. Therewas a normal foveal depression in the right eye. In the left eye therewas no sign of CME; rather, there was a stage II macular hole witha surrounding cuff of subretinal fluid (Figure 1C). A positiveWatzke–Allen sign was present. Repeat GVF examinations re-vealed field defects suggestive of bitemporal defects that obey thevertical midline and are consistent with the fundus findings (Figure2). Fluorescein angiography revealed no active CME; however,there was a retinal pigment epithelial window defect in the leftfoveal region (Figure 1D). Electroretinogram responses to scotopicand photopic stimuli were attenuated 40 to 60% in amplitude andthe implicit times were within the normal range. Single strandedconformational polymorphism DNA testing revealed no defects inthe rhodopsin or peripherin genes.

Typical vitrectomy/fluid–gas exchange (10% C3F8 gas) tech-nique with stripping of the internal limiting membrane, without theuse of adjuvants,1 was performed to treat the macular hole. Thepatient maintained face-down positioning for 1 week. The hole wasnoted to be closed (Figure 1E). Her VA after 3 months improvedto 20/30 and has remained at that level for 18 months.

Discussion

This case illustrates three important issues. First,sector RP usually presents in the nasal quadrant of thefundus.2 Sector RP nasal to the foveae resulting inbitemporal visual field defects is rare.3 In this case theGVF findings led the referring physician to obtainmagnetic resonance imaging to look for a centralchiasmal lesion. Second, macular holes in patientswith RP respond to standard surgical correction. Thishole may be a result of previous CME, but more likelyrepresents an idiopathic macular hole misdiagnosed asCME. Finally, this case illustrates that patients withRP are susceptible to non-RP–related eye disease andshows the importance of these patients receiving rou-tine eye examinations to rule out problems that mightbe masked by the RP.

Funded in part by NEI K1100347, P30EY06360 (a NIH Depart-ment Core Grant), The Foundation Fighting Blindness Wayne T.Robertson Young Investigator Award, and Research to PreventBlindness.

The author has no proprietary interest.Reprint requests: David A. Saperstein, MD, Department of Oph-

thalmology, Box 356485, The University of Washington, Seattle,WA 98195; e-mail: [email protected]

73BRIEF REPORTS

References1. Olsen TW, Sternberg P Jr, Capone A Jr, et al. Macular hole

surgery using thrombin-activated fibrinogen and selective re-moval of the internal limiting membrane. Retina 1998;18:322–329.

2. Krill AE, Archer D, Martin D. Sector retinitis pigmentosa.Am J Ophthalmol 1970;69:977–987.

3. Abraham FA. Sector retinitis pigmentosa. Electrophysiologi-cal and pyschophysiological study of the visual system. DocOphthalmol 1975;39:13–28.

Fig. 1. A, B, Digital composite photographs of right and left fundi, respectively. Note that the pigment spicules are only present nasal to the foveaein each eye. These findings are consistent with the Goldmann visual field examinations in Figure 2.C, Red-free photograph of the left fovea. Notethe macular hole (arrows) and the surrounding subretinal fluid (fat arrows).D, Late fluorescein angiogram of the left macula. There is an area in thefovea of hyperfluorescence at the level of the retinal pigment epithelium (RPE). This area most likely represents an RPE window defect due to themacular hole.E, Postoperative fundus photograph of the left eye 3 months after surgery. The macular hole is closed with resolution of subretinal fluid.

Fig. 2. Goldmann visual field of both the right (A) and left (B) eyes. The temporal field defects obey the vertical midline and are consistent withthe pigmentary changes in the fundus in Figure 1, A and B.


BILATERAL OCULAR ISCHEMICSYNDROME IN TAKAYASU DISEASE

MARTIN WORRALL, MD,*NEAL ATEBARA, MD,†TRAVIS MEREDITH, MD,‡ERIC S. MANN, MD, PHD§

From the *Baylor College of Medicine, Department ofOphthalmology, Houston, Texas; †Retina Associatesof Hawaii, Honolulu; and ‡Barnes Retina Institute and§Department of Ophthalmology, Saint Louis UniversityHealth Sciences Center, St. Louis, Missouri.

Takayasu or “pulseless” disease is a rare, idiopathic,chronic granulomatous large-vessel vasculitis involv-ing the aorta and its primary branches. Clinical man-ifestations relate to the anatomic site of vascular ob-struction and may be life threatening. Takayasudisease occurs predominantly in young Japanesewomen, but also rarely in black patients.1

Ocular manifestations occur as a consequence ofattenuation or obliteration of the carotids with ocularischemia. The retinal vascular changes progress fromgeneralized vasodilation and microaneurysmal forma-tion to arteriovenous shunts, vaso-obliteration, andproliferative retinopathy.2 Irreversible visual loss alsooccurs from anterior ischemic optic neuropathy3 andneovascular glaucoma.4 We report a case of bilateralocular ischemic syndrome in an black patient withTakayasu disease.

Case Report

A 49-year-old black woman was referred for loss of vision withocular pain in the left eye for 1 week. Fever, weight loss, malaise,and amaurosis fugax in the right eye occurred 12 years earlier. Thepatient appeared cachectic with absent carotid, brachial, and radial

pulse. Visual acuity measured 20/20 in the right eye and 20/50 inthe left with no relative afferent pupillary defect. Anterior segmentexamination was unremarkable. Posterior pole findings showedcotton-wool spots, venous dilation, and beading with moderatearterial narrowing (Figure 1A) in both eyes. Multiple intraretinalhemorrhages, microaneurysms, and telangiectasis extended to themidperiphery. Fluorescein angiography showed delayed arterialfilling and arteriovenous transit time with retinal vascular stainingparticularly the arterioles (Figure 1B) in both eyes. Panretinalphotocoagulation was not performed because there was no neovas-cularization of the iris, optic disk, or retina. Cardiac, carotid, andvascular evaluation was recommended.

Six days later the patient awoke with confusion, aphasia, andright-sided weakness. A cranial MRI revealed an acute left tem-poroparietal stroke. Carotid Doppler and thoracic angiogram dem-onstrated total occlusion of the left common carotid artery and rightand left subclavian arteries with near complete occlusion of theright common carotid artery, consistent with Takayasu disease.

She was lost to follow-up but returned 3 years later with visualacuity 3/200 in the right eye and light perception in the left withnormal intraocular pressures. The left cornea revealed 360° ofvascular ingrowth with no view of the fundus and complete angleclosure. The right eye showed 11 anterior chamber cell and flare,rubeosis iridis with 270° of angle closure, and progressive cataract.There was optic nerve pallor with collateral vessels on the disk andarteriovenous shunts within the macula. Arterial pulsations on thedisk were easily elicited with minimal pressure on the globe.Fluorescein angiography (Figure 2) revealed peripheral capillarynonperfusion. Panretinal photocoagulation and cataract extractionwithout intraocular lens placement was performed with regressionof rubeosis iridis. Visual acuity remains 20/320 in the right eyethrough 12 months of postoperative follow-up.

Discussion

The American College of Rheumatology criteria forTakayasu disease require three of the following sixfeatures of the disease: 1) onset at age 40 years oryounger, 2) claudication of the extremities, 3) de-creased pulsation in one or both brachial arteries, 4)systolic blood pressure difference of greater than 10mmHg between arms, 5) audible bruit over the aortaor at least one subclavian artery, and 6) arteriographicnarrowing or occlusion of the aorta, its primary

Reprint requests: Eric S. Mann, MD, PhD, Saint Louis Univer-sity Eye Institute, 1755 S. Grand Boulevard, St. Louis, MO 63104;e-mail: [email protected]

Fig. 1. A, Fundus photographof the left eye shows dilated,beaded retinal veins, cotton-wool spots, and microaneu-rysms.B, Fluorescein angio-gram of the left eye showsmicroaneurysms and late ret-inal vascular staining, primar-ily arterioles.

75BRIEF REPORTS

branches, or large vessels of the proximal upper orlower extremities. Our patient demonstrated all sixfeatures with ocular findings in both eyes consistentwith ocular ischemic syndrome. Systemic evaluationfailed to reveal any other known etiology.

Takayasu arteritis should be considered in the caseof retinal arteriovenous shunts2 or ocular ischemicsyndrome, particularly when accompanied by symp-toms of claudication, coldness, or weakness of theextremities, even in young, non-Asian patients. Al-though systemic steroids and immunosuppressiveagents may be used early in the disease, once retinal oranterior segment neovascularization occurs, panretinalphotocoagulation, cryoablation, or glaucoma surgicalprocedures are often necessary but may not halt dis-ease progression. This case shows the ocular manifes-tations of Takayasu disease and the important role ofthe ophthalmologist in disclosing a life-threateningsystemic vascular disease.

References1. Human GP. Takayasu’s arteritis—case report of an African

female. S Afr Med J 1967;41:445–447.2. Tanaka T, Shimizu K. Retinal arteriovenous shunts in Taka-

yasu’s arteritis. Ophthalmology 1987;94:1380–1388.3. Schmidt MH. Bilateral anterior ischemic optic neuropathy as a

presentation of Takayasu’s disease. J Neuro-ophthalmol 1997;17:156–161.

4. Karwatowski WSS, Jampol LM, Mani H, Weinreb RN. Neo-vascular glaucoma in Takayasu’s disease: a case report. Retina1995;15:353–354.

EPIPAPILLARY ADENOMA OF RETINALPIGMENT EPITHELIUM

JERRY A. SHIELDS, MD,*TOUFIC MELKI, MD,‡CAROL L. SHIELDS, MD,*RALPH C. EAGLE, JR, MD,†ARUN D. SINGH, MD*

From the *Oncology Service and the †Department ofPathology, Wills Eye Hospital, Thomas Jefferson Uni-versity, Philadelphia, Pennsylvania; and the ‡Depart-ment of Ophthalmology, Georgetown University,Washington, DC.

Adenoma of retinal pigmented epithelium (RPE) is arare tumor that can simulate choroidal melanoma.1

Features that help differentiate RPE adenoma frommelanoma have been elucidated.2 Most RPE adeno-mas are located in peripheral retina and it is extremelyrare for an adenoma of the RPE to arise posteriorlyand grow to obscure the optic disk. We report aclinicopathologic correlation of a juxtapapillary RPEadenoma that enlarged and covered the optic disk,suggesting malignant transformation of a melanocy-toma into a malignant melanoma.

Case Report

In 1976, an asymptomatic 22-year-old man was found to have a“nevus” on the margin of his left optic disk. He was examined overthe next 23 years by several ophthalmologists, each of whomassured him that the lesion was benign and stable.

In August 1999, he experienced sudden visual loss in the left eye.His visual acuity was 6/6 in the right and 6/7.5 in the left eye. A deeplypigmented mass, much larger than noted previously, obscured the leftoptic disk. It measured 6.53 5.5 mm in diameter and 4.5 mm inthickness, confirmed with ultrasonography. Yellow circinate intrareti-nal exudation and subretinal fluid were present on the inferior andnasal borders of the lesion (Figure 1). Pigmented cells emanated fromthe mass to infiltrate the vitreous inferiorly. There was a tractionalretinal hole between the equator and ora serrata superonasally. Fluo-rescein angiography showed the mass to be relatively hypofluorescentin the early angiograms and to have slight overlying leakage of dye inthe late angiograms. There was intense late staining of the surroundingsubretinal fluid and exudation (Figure 2). A- and B-scan ultrasonog-raphy revealed the mass to have medium internal reflectivity. Wecould not obtain prior photographs but the patient recalled that thelesion was described as “small and benign.”

Supported by the Eye Tumor Research Foundation, Philadelphia,PA, the Award of Merit in Retina Research, Houston, TX (Dr. J.Shields), the Macula Foundation, New York, NY (Dr. C. Shields), andthe Noel T. Sara L. Simmonds Endowment for Ophthalmic Pathology,Wills Eye Hospital, Philadelphia, PA (Dr. Eagle).

Presented at the annual Wills Eye Hospital Retina Conference;Philadelphia, PA; November 12, 1999 (Dr. Melki).

Reprint requests: Jerry A. Shields, MD, Director, OncologyService, Wills Eye Hospital, 900 Walnut Street, Philadelphia, PA19107.

Fig. 2. Fluorescein angiogram of the right eye (3 years after previousfluorescein angiogram; Figures 1) shows collaterals on the optic diskand retinal arteriovenous shunts at arteriovenous crossings (arrows)with vaso-obliteration of peripheral neighboring capillaries.


Our differential diagnosis included 1) melanoma arising fromoptic disk melanocytoma, 2) necrotic melanocytoma, and 3) RPEadenoma. The patient was informed of the diagnostic possibilitiesand was offered observation, needle biopsy, or enucleation. Heelected to undergo enucleation because of concern aboutmalignancy.

Gross and microscopic examination disclosed an intensely pig-mented tumor that measured 53 5 3 4 mm and appeared to arisefrom and cover the optic disk (Figure 3). Microscopically, it wascomposed of cords and tubules of RPE cells (Figure 4), separatedby periodic acid-Schiff–positive basement membrane. The tumorwas continuous with the RPE and focally invaded the choroid,sensory retina, and vitreous. There was localized juxtapapillaryretinal detachment with lipoproteinaceous intraretinal exudation.The diagnosis was adenoma of the RPE, presumably arising adja-cent to the optic disk.

Discussion

The features that help differentiate adenoma of theRPE from choroidal melanoma have been elucidated.2

RPE adenoma usually occurs in the peripheral retinaand rarely arises in a juxtapapillary location.3–5To ourknowledge, however, RPE adenoma has not been pre-

viously documented to grow entirely over and obscurethe optic disk. Such a finding is more consistent withan optic nerve melanocytoma or juxtapapillary mela-noma. In retrospect, the circinate exudation is moresuggestive of adenoma of the RPE2 but is rare withmelanocytoma or choroidal melanoma. However, inour case, a melanoma could not be absolutely ex-cluded based on clinical findings.

In summary, this case demonstrates that adenomaof the RPE can occur on the optic disk and producevitreous seeding, suggesting malignant transformationof a melanocytoma. Although these pigmented lesionscan be quite similar, the presence of exudative reti-nopathy should suggest adenoma of the RPE, ratherthan melanocytoma or melanoma.

.

References1. Shields JA, Shields CL. Tumors of the retinal pigment epithe-

lium. In: Shields JA, Shields CL. Atlas of Intraocular Tumors.Philadelphia: Lippincott Williams & Wilkins, 1999:288–292.

2. Shields JA, Shields CL, Gunduz K, Eagle RC Jr. Neoplasms of

Fig. 1. Fundus photograph shows deeply pigmented epipapillary masswith surrounding circinate exudation.

Fig. 2. Fluorescein angiog-raphy. A, Full venous phaseshows hypofluorescence ofthe mass.B, Late angiogramshows minimal leakage ofdye into the center of themass and more intense stain-ing around the mass corre-sponding to the exudation andsubretinal fluid.

Fig. 3. Elevated, solid, pigmented mass lying directly over the opticdisk (hematoxylin-eosin, original magnification3 10).

77BRIEF REPORTS

the retinal pigment epithelium. The 1998 Albert Ruedemann Sr.Memorial Lecture. Part 2. Arch Ophthalmol 1999;117:601–608.

3. Shields JA, Eagle RC Jr, Shields CL, De Potter P. Pigmentedadenoma of the optic nerve head simulating a melanocytoma.Ophthalmology 1992;99:1705–1708.

4. Loose IA, Jampol LM, O’Grady R. Pigmented adenoma mim-icking a juxtapapillary melanoma. Arch Ophthalmol 1999;117:120–122.

5. Shields JA, Eagle RC Jr, Barr CC, Shields CL, Jones DE.Adenocarcinoma of the retinal pigment epithelium arisingfrom a juxtapapillary histoplasmosis scar. Arch Ophthalmol1994;112:650–653.

OPTICAL COHERENCE TOMOGRAPHYAND ELECTROPHYSIOLOGY IN X-LINKEDJUVENILE RETINOSCHISIS ASSOCIATEDWITH A NOVEL MUTATION IN THEXLRS1 GENE

PAULO E. STANGA, MD,*N.H. VICTOR CHONG, FRCOPHTH,*ANNE C. RECK, FRCOPHTH,*ALISON J. HARDCASTLE, PHD,†GRAHAM E. HOLDER, PHD‡

From the *Department of Clinical Ophthalmology,Moorfields Eye Hospital and Institute of Ophthalmol-ogy; the †Department of Molecular Genetics, Institu-teof Ophthalmology; and ‡Department of Electro-physiology, Moorfields Eye Hospital, London, UnitedKingdom.

We describe optical coherence tomography (OCT)and electrophysiology findings in X-linked juvenileretinoschisis (XLRS) associated with a novel mutationin the XLRS1gene.

A 39-year-old man had been diagnosed with mac-ular dystrophy in early childhood. There was no fam-ily history. Right visual acuity had been 20/120 fromchildhood, and left acuity dropped from 20/40 to 20/200 over 20 years. The fundal appearance is shown inFigure 1, A and B.

Optical coherence tomography single line bilaminarscans of the posterior pole region were performedusing the OCT 2000 scanner (Zeiss Humphrey Instru-ments, San Leandro, CA). Electroretinogram (ERG),pattern ERG (PERG), and ON–OFF responses wererecorded using standardized methods (International So-ciety for Clinical Electrophysiology of Vision [ISCEV]).

Sequence analysis of theXLRS1gene was carriedout to obtain genetic confirmation of the disease. Allsix exon fragments of theXLRS1gene were amplifiedwith intronic primers.1 Polymerase chain reaction wascarried out in 25-mL reactions in the presence of 0.5 UTaq polymerase (Biotaq; Bioline, London, UK); 200mmol/L each of dATP, dCTP, dGTP, and dTTP; 200pmol of each primer; and 13 KCl reaction buffer(Bioline) including 1.5 mmol/L MgCl2. Polymerasechain reaction conditions were as described by Saueret al.1 Amplification products were purified with cen-tricon concentrators (Amicon Limited, Gloucester-shire, UK) following manufacturer’s instructions. Thepurified DNA sample (5mL) was cycle sequenced inboth directions (with primers used for amplification)using ABI prism Ready Reaction dye terminationcycle sequencing kit (FS kit, Perkin Elmer AppliedBiosystems, Warrington, UK) following manufactur-er’s instructions. Reactions were then electrophoresedon an ABI 373A sequencer.

Electrophysiology (Figure 2) showed marked gen-eralized postreceptor dysfunction with macular in-volvement, compatible with XLRS. Note the absentrod ERG, the electronegative maximal ERG, the am-plitude and implicit time changes in photopic andflicker ERG, and the marked PERG reduction, thelatter indicating the macular dysfunction. The reduc-tion in both ON- b-wave and OFF- d-wave, withsparing of the ON- a-wave, suggested involvement ofboth depolarizing and hyperpolarizing photopic path-ways. Optical coherence tomography demonstrates acleavage plane in neural retina (Figure 3).

Direct sequencing of theXLRS1gene revealed a splicedonor mutation in intron 1 (521 2 t3 c) (Figure 4).This t-to-c substitution at the splice donor site of intron 1disrupts a nucleotide that is 100% conserved and ispredicted to result in a lack of protein product.

None of the authors has a proprietary interest.P.E. Stanga is supported by the Lady Anne Allerton Fund,

London, UK.Reprint requests: G.E. Holder, PhD, Department of Electrophys-

iology, Moorfields Eye Hospital, 162 City Road, London EC1V2PD, UK; e-mail: [email protected]

Fig. 4. Bleached section shows cords of epithelial cells, consistentwith adenoma of the retinal pigment epithelium (bleached sections,hematoxylin-eosin, original magnification3 200).


Discussion

X-linked juvenile retinoschisis is a recessively in-herited vitreoretinal degeneration characterized bymacular pathology and intraretinal splitting of theretina that may be associated with alterations in theXLRS1gene.2 The characteristic foveal cystic changesin XLRSmay disappear in adulthood with the devel-opment of nonspecific atrophic lesions. Only 50%have peripheral schitic changes.3 Histopathologically,the splitting occurs in the nerve fiber layer, and mayreflect Müller cell abnormality.4 The cleavage planelocation may be determined by OCT,5 enabling invivo imaging of schisis even when it is not evident onbiomicroscopy. Typical electrophysiology confirmsgeneralized postreceptor retinal dysfunction.

This brief report illustrates the combined value ofOCT and electrophysiology in suspected retinoschisis,and describes a novel mutation.

References1. Sauer CG, Gehrig A, Warneke-Wittstock R, et al. Positional

cloning of the gene associated with X-linked juvenile retino-schisis. Nat Genet 1997;17:164–170.

2. The Retinoschisis Consortium. Functional implications of thespectrum of mutations found in 234 cases with X-linked ju-venile retinoschisis (XLRS). Hum Mol Genet 1998;7:1185–1192.

3. Gass JDM. Stereoscopic Atlas of Macular Diseases, 3rd ed. StLouis: CV Mosby, 1987;1:292.

4. Manschot WA. Pathology of hereditary juvenile retinoschisis.Arch Ophthalmol 1972;88:131.

5. Rutledge BK, Puliafito CA, Duker JS, et al. Optical coherence

Fig. 1. A, Color fundus pho-tograph of the right eye showsnonspecific foveal changes(solid black line indicates theoptical coherence tomogra-phy scan plane in Figure 4).B, Color fundus photographof the left eye shows classicperipheral schitic changes.

Fig. 2. Electrophysiologic findings in the patient show an electronegative electroretinogram with a bright white flash, typical of X-linkedretinoschisis. See text for further details.

79BRIEF REPORTS

tomography of macular lesions associated with optic nerve-head pits. Ophthalmology 1996;103:1047–1053.

DIABETIC PAPILLOPATHY WITHMACULAR STAR MIMICKINGCLINICALLY SIGNIFICANT DIABETICMACULAR EDEMA

YOLANDA FRIEDRICH, MD,MICHAEL FEINER, MD,HAYTHUM GAWI, MD,ZVI FRIEDMAN, MD

From The Annette and Aron Rozin Department ofOphthalmology, Bnai–Zion Medical Center, Facultyof Medicine, Haifa, Israel.

Optic disk edema occurring in young people with typeI diabetes mellitus (DM) has been described by sev-eral investigators.1-3 The usual presentation is tran-sient unilateral or bilateral optic disk swelling associ-ated with minimal or no permanent visual deficit.Similar cases have been reported later in older pa-tients, most of them with type II DM. Regillo et al4

described 19 patients (27 eyes) with disk edema,13 ofwhom had type II DM. Of the 27 eyes, 19 had diabeticmacular edema (DME), 6 of which required lasertreatment. In two eyes the macular edema seemed tobe an extension of the disk edema. We present threecases—one bilateral, two unilateral (four eyes)—ofdiabetic optic disk swelling and marked decrease ofvisual acuity associated with macular edema present-ing as macular star, originating from the disk capil-laries, mimicking clinically significant DME(CSDME).

Materials and Methods

Three patients with DM, background diabetic reti-nopathy (BDR), and optic disk swelling—one bilat-eral, two unilateral—were seen in whom the diskswelling was associated with contiguous macularedema and a macular star. Detailed clinical informa-tion was obtained on each patient including completeeye examination, fluorescein angiography, and Gold-mann perimetry. Systemic evaluation, blood tests, andbrain computerized tomography (CT) scan were per-formed to rule out other causes of disk swelling.

Reprint requests: Zvi Friedman, MD, The Annette & Aron RozinDepartment of Ophthalmology, Bnai–Zion Medical Center, Fac-ulty of Medicine, The Technion, 47, Golomb St., Haifa 31048,Israel.

Fig. 3. A, Single line optical coherence tomography (OCT) scan of theright eye, which demonstrates a cleavage plane in the neural retina notevident on biomicroscopy.B, Higher magnification OCT of the lefteye, which demonstrates a cleavage plane in the neural retina withbridging retinal elements.

Fig. 4. Electropherogram depicts patient mutation at position (5212 t3 c) in intron 1 of theXLRS1gene.


Results

Four eyes (three patients, all with type II DM)presented with diabetic papillopathy associated withcontiguous macular edema during the years 1996 to1998. Age ranged between 65 and 67 years.

In all eyes there was moderate BDR, swelling of theoptic nerve head, flame shaped hemorrhages, andmacular edema with hard exudates mimickingCSDME. The main distinguishing feature fromCSDME was the star configuration of these exudatesrather than a circinate pattern (Figure 1A).

All affected eyes had severe visual loss with visualacuity at presentation ranging from 1/60 to 5/60.There was a relative afferent pupillary defect (RAPD)in the two unilateral cases. Goldmann perimetry re-vealed cecocentral scotoma.

Fluorescein angiography (Figure 1, B and C) con-firmed the presence of BDR and demonstrated mod-erate to marked late staining extending from the disk.There was no or only mild dye leakage from perifo-veal capillaries. Neither capillary nonperfusion norproliferative diabetic retinopathy was detected in anyof the eyes. In all patients, blood pressure measure-ment, brain CT scan, chest X rays, purified proteinderivative skin test, blood sedimentation rate, angio-tensin converting enzyme, and blood serology re-vealed no abnormal finding. There was no history ofrecent tightening of the glycemic state by intensiveinsulin treatment. Because diabetic papillopathy wasthe assumed diagnosis no treatment was applied. Inthree of the eyes the disk edema and flame shapedhemorrhages as well as the macular edema and mac-ular star resolved spontaneously after 1 to 8 monthsand visual acuity improved, ranging from 6/6 to 6/12with disappearance of the RAPD and central sco-tomata. The remaining patient was lost to follow-up.A year later three eyes (two patients) developed

CSDME and underwent modified grid laser photo-coagulation.

Discussion

A syndrome of idiopathic transient optic diskedema with minimal or no clinical evidence of per-manent visual loss in young, insulin-dependent dia-betic patients was described in 1971 by Lubow andMakley.1 Since then, a similar clinical picture hasbeen described in patients with type II DM.4,5

To our knowledge, no reference to a macular starconfiguration of hard exudates was made in thesecases, although Regillo et al4 noted macular edemaextending from the disk in a few patients. The inci-dence of diabetic papillopathy is difficult to estimate.Barr et al3 reported a frequency of 0.4% among alldiabetic patients seen by an ophthalmologist.

In the clinical context of DM, disk swelling, de-creased visual acuity, normal systemic blood pressure,the absence of symptoms of increased intracranialpressure, and a normal brain CT scan, an intrinsicoptic nerve head vasculopathy (diabetic papillopathy)should be considered. Visual field defect, which inearly papilledema presents as an enlarged blind spot,manifests as a central scotoma, arcuate scotoma, orsector scotoma in diabetic papillopathy3—patternssimilar to those found in our series.

Anterior ischemic optic neuropathy (AION) is themost common cause of optic disk edema in subjectsover the age of 55 and is believed to be the result ofocclusion of branches of the short posterior ciliaryarteries supplying the optic nerve head.6 Twenty per-cent of patients with AION, especially below the ageof 64, also have DM.7 Visual loss in patients withAION is usually sudden and frequently permanent,and disk pallor usually results after the swelling re-solves. In the current series, three of the four eyes

Fig. 1. Left eye of Case 1, 2 days after presentation.A, Fundus photograph shows disk edema with multiple flame shaped hemorrhages and macularedema with star configuration of hard exudates.B, Fluorescein angiography, arteriovenous phase. Multiple flame shaped hemorrhages maskbackground fluorescence. Scattered leaking capillaries due to background diabetic retinopathy. Capillary bed is intact.C, Fluorescein angiography,late phase. Dye leakage extends from disk.

81BRIEF REPORTS

regained vision of 6/6 to 6/12 within 1 to 8 months;the remaining eye was lost to follow-up. The recoveryof final visual acuity in two of our patients is incontrast to the optic atrophy and permanent visual lossusually seen in patients with AION.

Macular star formation of hard exudates indicatesmarked permeability of the disk capillaries. To ourknowledge it has never been seen in AION.

Gass8 suggested that the star-shaped pattern of hardexudates is due to leakage from prelaminar disk cap-illaries. Fluid spreads from the disk through the outerplexiform layer of the retina and accumulates in Hen-le’s layer. The unique anatomy of this layer accountsfor the formation of the radially oriented macular starfollowing the absorption of the edematous fluid andthe precipitation of lipoproteins. It is common in neu-roretinitis and malignant hypertension,9 which werenot present in our cases. We describe four eyes ofthree patients with type II DM who developed diskedema associated with macular edema and a star for-mation of hard exudates. According to the EarlyTreatment Diabetic Retinopathy Study,10 the presenceof hard exudates within 500mm from the center of thefovea associated with retinal thickening (CSDME) isan indication for laser treatment; however, in caseswhere such exudates assume a star configuration ratherthan a circinate pattern and are associated with diskedema, fluorescein angiography determines the origin ofthese exudates to be from the disk and not from theperifoveal capillaries, obviating the need for laser treat-ment. Repeat blood pressure measurement is importantto exclude malignant hypertension as the causative fac-tor. These exudates often disappear without treatment assoon as the disk edema subsides, leading to recovery ofvisual acuity. Further follow-up is needed to detect CS-DME that can develop later, as happened in two of ourpatients and required laser treatment.

References1. Lubow M, Makley TA. Pseudopapilledema of juvenile dia-

betes mellitus. Arch Ophthalmol 1971;85:417–422.2. Pavan PR, Aiello LM, Wafai MZ, Briones JC, Sebestyen JB,

Bradbury MJ. Optic disc edema in juvenile-onset diabetes.Arch Ophthalmol 1980;98:2193–2195.

3. Barr CC, Glaser JS, Blankenship G. Acute disc swelling injuvenile diabetes. Clinical profile and natural history of 12cases. Arch Ophthalmol 1980;98:2185–2192.

4. Regillo CD, Brown GC, Savino PJ, Byrnes GA, Benson WE,Tasman WS. Diabetic papillopathy. Patient characteristicsand fundus findings. Arch Ophthalmol 1995;113:889–895.

5. Barrett K. Disc swelling in an adult diabetic patient. SurvOphthalmol 1990;35:158–163.

6. Miller NR. Anterior ischemic optic neuropathy: diagnosisand management. Bull NY Acad Med 1980;56:643–654.

7. Repka MX, Savino PJ, Schatz NJ, Sergott RC. Clinicalprofile and long term implication of anterior ischemic opticneuropathy. Am J Ophthalmol 1983;96:478–483.

8. Gass JDM. Disease of the optic nerve that may simulatemacular disease. Trans Am Acad Ophthalmol Otolaryngol1977;83:763–770.

9. Tso MOM, Jampol LM. Pathophysiology of hypertensiveretinopathy. Ophthalmology 1982;89:1132–1145.

10. The Early Treatment of Diabetic Retinopathy Study ResearchGroup. Photocoagulation for diabetic macular edema. ArchOphthalmol 1985;103:1796–1806.

SURGICAL MANAGEMENT OF COMBINEDTRACTION AND RHEGMATOGENOUSRETINAL DETACHMENT ASSOCIATEDWITH PERSISTENT FETAL VASCULATURE

JOHN O. MASON III, MD

From the University of Alabama at BirminghamSchool of Medicine.

Persistent hyperplastic primary vitreous (PHPV), acongenital anomaly in which the embryonic hyaloidvasculature fails to regress normally, was first de-scribed by Reese in 1955.1 Goldberg, in 1997, re-named PHPV persistent fetal vasculature (PFV).2 Persis-tent fetal vasculature has been separated into anterior,posterior, and combined anterior/posterior, depending onwhich ocular structures are involved. This report de-scribes an infant who underwent a scleral buckle proce-dure for combination traction and rhegmatogenous reti-nal detachment (RD) secondary to PFV.

Case Report

A 3-month-old, full-term girl was noted to have right facial andlid capillary hemangiomas. The referring ophthalmologist discov-ered a retinal abnormality and referred the patient for furtherevaluation. On examination, the patient had right facial and lidcapillary hemangiomas. The anterior segment examination re-vealed a posterior polar lenticular density with a small retrolentalmembrane. The nasal ciliary processes were elongated (Figure 1).The vitreous was clear and the optic nerve was normal. A thinvitreous stalk was present from the posterior lens to the optic nerve.The retina was totally detached and traction folds were noted in thefar nasal periphery. The left eye was normal.

Examination under anesthesia of the right eye revealed theelongated nasal ciliary processes with taut vitreous bands extend-ing from the ciliary processes to the nasal retina near the oraserrata. The retina appeared to attach at the pars plicata and a smallstretch retinal break was noted between retinal folds and tautvitreous bands nasally approximately 2 mm from the anteriorretinal edge.

As the posterior polar cataract and the vitreous stalk were mildand the vitreous was relatively clear, vitrectomy and lensectomy

Supported by Research to Prevent Blindness departmental grant.Reprint requests: John O. Mason, III, MD, Assistant Professor of

Ophthalmology and Vitreoretinal Surgery, University of Alabamaat Birmingham School of Medicine, 700 South 18th Street, Suite505, Birmingham, AL 35233; e-mail: [email protected]


surgery was not performed. Instead, an encircling scleral buckleprocedure using a wide band nasally was performed without com-plication and the retina was attached on postoperative day 1.Amblyopia therapy was initiated. Nine months postoperatively, theencircling band was segmented. One year postoperatively, theretina remains attached and the patient fixes and follows.

Discussion

Multiple surgical procedures have been advocatedfor management of PFV. Most earlier papers reporteddismal results for surgical management of posteriorPFV.1,3 Recently, improved vitrectomy techniqueshave improved the surgical success rates for posteriorPFV or combined anterior/posterior PFV.4,5

This case differs from most cases of PFV by virtueof having a combined traction and rhegmatogenousRD without any posterior fundus vitreoretinal adhe-sions being present. It appears as though the elonga-tion of the nasal ciliary processes (causing tractionalfolds of the nasal retina) and abnormal vitreoretinalattachments (taut bands) in the nasal periphery causeda stretch hole to develop, leading to a combined trac-tion and rhegmatogenous RD. Pruett and Schepenshave suggested that congenital vitreoretinal adhesionsmay cause rhegmatogenous RD.6

This case also differs by its surgical management.The majority of posterior segment PFV is managedvia vitrectomy. This is primarily due to the prevalenceof either posterior pole vitreoretinal membranes orstalk, dense cataract, or RD. Dass and Trese5 de-scribed surgical management of 27 cases of PFV and

used a scleral buckle procedure on only two cases.One case failed and the other case preoperatively hada traction RD and did not have a total RD or arhegmatogenous component.

Persistent fetal vasculature has a spectrum of pre-sentation anteriorly and posteriorly. Elongation of theciliary processes in combination with an abnormalvitreoretinal adhesion (taut bands) can lead not only totraction RD, but also to rhegmatogenous RD. Patientsshould be carefully examined for a retinal break.When a rhegmatogenous component is present in ad-dition to vitreous traction, the rhegmatogenous com-ponent may be the primary cause of the detachment.In this type of scenario, a scleral buckle procedurealone can result in a surgical success by closing theretinal break and limiting the tractional forces on theretina in the far periphery.

References1. Reese AB. Persistent hyperplastic primary vitreous. Am J

Ophthalmol 1955;40:317–331.2. Goldberg MF. Persistent fetal vasculature (PFV): an integrated

interpretation of signs and symptoms associated with persis-tent hyperplastic primary vitreous (PHPV). Am J Ophthalmol1997;124:587.

3. Pollard ZF. Results of treatment of persistent hyperplasticprimary vitreous. Ophthalmic Surg 1991;22:48–52.

4. Mittra RA, Huynh LT, Ruttum MS, et al. Visual outcomesfollowing lensectomy and vitrectomy for combined anteriorand posterior persistent hyperplastic primary vitreous. ArchOphthalmol 1998;116:1190–1194.

5. Dass DA, Trese MT. Surgical results of persistent hyperplasticprimary vitreous. Ophthalmology 1999;106:280–284.

6. Pruett RC, Schepens CL. Posterior hyperplastic primary vitre-ous. Am J Ophthalmol 1970;69:534–543.

CENTRAL RETINAL VEIN OCCLUSIONASSOCIATED WITH PRIMARYPULMONARY HYPERTENSION

A. BHAN, FRCOPHTH,I.G. RENNIE, FRCOPHTH,T.W. HIGENBOTTAM, FRCP

From Royal Hallamshire Hospital, Sheffield, UnitedKingdom.

Primary pulmonary hypertension (PPH) is an un-usual condition that has rarely been associated withocular abnormalities.

Reprint requests: A. Bhan, FRCOphth, Department of Ophthal-mology, Queens Medical Centre, Nottingham, NG7 2UH, UK;e-mail: [email protected]

Fig. 1. External photograph of the right eye shows lid capillary hem-angiomas, very elongated nasal ciliary processes, posterior iris syn-echiae, and a posterior polar lens opacity; a light reflex is present nasalto the lens opacity.

83BRIEF REPORTS

Case Report

A 37-year-old woman presented to us with blurred vision in herleft eye. She had developed this symptom 12 months previously.The onset was sudden and the resolution gradual. Following res-olution she experienced fluctuation of vision in that eye. Hermedical history included right-sided refractive amblyopia andPPH. The latter had been present for over 18 months before thispresentation, and her mean pulmonary arterial pressure was foundto be 48 mmHg. The patient had undergone tests to exclude causesof secondary pulmonary hypertension including liver functiontests, autoantibodies, human immunodeficiency virus–1 screening,electrocardiography, chest x-ray, pulmonary function tests, and aventilation-perfusion scan. At the time of presentation, she wastaking isosorbide mononitrate, diuretics, and warfarin. She was nottaking oral contraceptives and there was no family history of note.

Examination revealed her vision to be 6/60 in the right eye and6/18 in the left, with best spectacle correction. Anterior segment

examination revealed marked episcleral vessel dilation in botheyes, normal and symmetric intraocular pressures, and no relativeafferent pupillary defect (Figure 1). Fundal examination revealedsigns in keeping with a left-sided central retinal vein occlusion:unilateral disk swelling, venous tortuosity, blot retinal hemor-rhages, and macular edema (Figure 2). Her clotting factors, includ-ing protein C, protein S, factor V Leiden, and anticardiolipinantibodies, were normal.

Discussion

Pulmonary hypertension is defined as a mean pul-monary arterial pressure of more than 25 mmHg atrest or more than 30 mmHg during exercise. Primarypulmonary hypertension is a rare condition, with an

Fig. 2. Red-free fundus pho-tographs of the left eye showa central retinal vein occlu-sion (A), with the normalright eye shown for compari-son (B). Fluorescein angiog-raphy of the left eye showsearly phase masking by thehemorrhages of the centralretinal vein occlusion (C) andthe late phase shows dilationand tortuosity with staining ofthe venous walls and peripap-illary leakage (D).

Fig. 1. Red-free anterior segment photographs of both eyes demonstrate episcleral injection.


incidence of 1 to 2 cases per million per year and aprevalence of 1300 per million. Its etiology is un-known although 10% of cases are familial and it has apredilection for young to middle-aged females. Cur-rent theories on pathogenesis focus on abnormalitiesin the interaction between endothelial and smoothmuscle cells. Clinical features include those resultingfrom hypoxia and cor pulmonale. Typically, patientsinitially develop dyspnea, which they attribute to be-ing unfit. This worsens and they may develop chestpain from right heart ischemia and syncopal episodesbefore signs of right heart failure.

The mainstay in the current treatment of severePPH is chronic intravenous infusion of prostacyclin,which improves survival and quality of life.1 Earlierstages of the disease can be treated with warfarinanticoagulation. Some patients are given vasodilators.Such treatments have been shown to enhance survival.Right ventricular dysfunction is thought to be revers-ible if normal pulmonary artery pressures are restored.Heart–lung transplantation is now undertaken for pa-tients in whom medical treatments are unsuccessful.The prognosis for untreated PPH is poor—mean sur-vival rates are 2 to 3 years from diagnosis.

Primary pulmonary hypertension is infrequently as-sociated with ocular abnormalities. Single case reportsof patients with bilateral uveal effusions2 and exuda-tive retinal detachment3 have been reported, as well asone case of a central retinal vein occlusion in conjunc-tion with purpura and livedo reticularis.4 Eisen-menger’s syndrome (secondary pulmonary hyperten-sion) has been associated with chronic ocularischemia.5 We hypothesize that right-sided heart fail-ure and raised venous pressure contribute to this con-dition. To our knowledge, this is the second report ofthis association.

References1. Higenbottam T, Stenmark K, Simmoneau G. Treatments for

severe pulmonary hypertension. Lancet 1999;353:338–340.2. Akduman L, Del Priore LV, Kaplan HJ, Meredith T. Uveal

effusion syndrome associated with primary pulmonary hyper-tension and vomiting. Am J Ophthalmol 1996;121:578–580.

3. Gislason I, Jonasson F, Stefansson E. Exudative retinal de-tachment in familial pulmonary hypertension. Acta Ophthal-mol 1991;69:805–809.

4. Berliner S, Shoenfeld Y, Dean H, et al. Primary pulmonaryhypertension: a facet of a diffuse angiopathic process? Respi-ration 1982;43:76–79.

5. Harino S, Motokura M, Nishikawa N, et al. Chronic ocularischaemia associated with the Eisenmenger’s syndrome. Am JOphthalmol 1994;117:302–307.

NEOVASCULARIZATION ASSOCIATEDWITH CYTOMEGALOVIRUS RETINITIS

GEMINI J. BOGIE, MD,SUMIT K. NANDA, MD

From the Department of Ophthalmology, Dean A.McGee Eye Institute, University of Oklahoma Collegeof Medicine, Oklahoma City.

Cytomegalovirus (CMV) retinitis is the most commoncause of blindness in patients with acquired immuno-deficiency syndrome (AIDS). Retinal vascular inflam-mation and attenuation are components of the retini-tis.1 We report two cases of neovascularizationoccurring in patients with human immunodeficiencyvirus (HIV) and CMV retinitis without other causes ofretinal ischemia. A case of neovascularization associ-ated with both CMV retinitis and cryptococcal cho-roiditis was reported in 1996.2 A case of optic diskneovascularization after branch retinal vein occlusionand branch retinal artery occlusion in association withHIV and CMV retinitis was also reported in 1996.3

Optic disk neovascularization was reported in a pa-tient with inactive CMV retinitis without capillarynonperfusion and with immune recovery vitritis.4

Case 1

A 43-year-old man with AIDS was diagnosed with CMV reti-nitis when he experienced bilateral blurred vision and floaters. Hismedical history included HIV positivity for 6 years, oral candidi-asis,Pneumocystis cariniipneumonia, AIDS-related anemia, anddisseminated CMV infection. He had previously been treated withintravenous (IV) ganciclovir with a neutropenic response. Currentmedications included zidovudine, IV foscarnet, and trimethoprim-sulfamethoxazole.

His visual acuity (VA) was 20/80 in the right eye and 20/40 inthe left eye. Anterior segment examinations were normal. Vitreouscell was present in both eyes. Fundus findings included scatteredintraretinal infiltrates and retinal hemorrhages, as well as vascularattenuation (Figure 1A). At that time, therapy for CMV infectionwas changed from IV foscarnet to IV ganciclovir.

One year after initial diagnosis of CMV retinitis, VA was handmotion in the right eye and 20/60 in the left eye. His CD4 count atthat time was 10. His medical regimen included zidovudine, lami-vudine, and maintenance IV ganciclovir. On the right, he had aprominent afferent pupillary defect and very hazy vitreous. Retinalpigmentary changes were present bilaterally without activeretinitis.

Four months later the patient returned with no light perception inthe right eye and 20/70 VA in the left eye. His CD4 count hadincreased to 184. He wasreceiving both ganciclovir and foscarnet IV.Examination findings included hazy vitreous on the right with opticnerve pallor and retinal pigmentary changes. Cellophane maculopathy,cystoid macular edema, retinal pigmentary changes, and neovascular-

Reprint requests: Gemini J. Bogie, MD, 608 Stanton L. YoungBlvd., Oklahoma City, OK 73104.

85BRIEF REPORTS

ization along the inferotemporal arcade (Figure 1B) were present inthe left eye. Fluorescein angiography of the left eye confirmed focalareas of nonperfusion inferiorly, with early hyperfluorescence andprogressive leakage consistent with neovascularization (Figure 1, Cand D). The patient was subsequently lost to follow-up.

Case 2

A 50-year-old man was diagnosed with CMV retinitis when heexperienced blurred vision, floaters, redness, and photophobia ofthe right eye. His medical history included HIV positivity for 12years and treated syphilis with a currently negative rapid plasmareagin status. His CD4 count was approximately 200. His medica-tions included indinavir, lamivudine, dapsone, and stavudine.

His VA was 20/250 in the right eye and 20/20 in the left eye.Intraocular pressure (IOP) was 31 on the right and 18 on the left.Significant anterior and posterior cell was present in the right eyeonly. Right fundus findings included frosted branch angiitis alongthe major vascular arcades and white intraretinal infiltrates withretinal hemorrhages inferiorly (Figure 2A). The left fundus was

normal. The patient’s elevated IOP and uveitis were treated withtopical medications.

After induction therapy with IV ganciclovir, he continued tohave IOP elevation, but resolving uveitis and retinitis. Retinalarterioles had sclerosed. A moderate amount of neovascularizationof the iris was present with involvement of the trabecular mesh-work inferiorly (Figure 2B). Panretinal photocoagulation was per-formed after fluorescein angiography, which revealed delayed ve-nous filling, diffuse capillary nonperfusion, and no earlyhyperfluorescence or late leakage (Figure 2C). YAG cyclophotoa-blation was performed for continued elevated IOP despite maximaltopical and oral medication. These therapies were successful inlowering the IOP and causing regression of the irisneovascularization.

Approximately 5 months after diagnosis of rubeotic glaucoma,neovascularization of the disk was noted. Panretinal photocoagu-lation was repeated, with regression of the neovascularizationwithin 3 weeks. The patient was eventually tapered off of thetopical steroid, and his secondary cataract was extracted, resultingin a best-corrected VA of 20/80.

Fig. 1. Case 1.A, Hazy vitreous, scattered retinal infiltrates, hemorrhages, cotton wool spots, andvascular attenuation at the time of diagnosis of cytomegalovirus (CMV) retinitis.B, Retinalpigmentary changes and vascular attenuation located inferotemporally, with a tuft of neovasculaturealong the inferotemporal arcade approximately 14 months after diagnosis of CMV retinitis.C,Fluorescein angiogram shows focal areas of capillary nonperfusion with early hyperfluorescencealong the inferotemporal arcade.D, Fluorescein angiogram shows progressive leakage alonginferotemporal arcade in area corresponding to tuft of neovascularization seen clinically.

Fig. 2. Case 2.A, Hazy vitreous, frosted branch angiitis along major vascular arcades, and intraretinal infiltrates and hemorrhages located inferiorlyat the time of diagnosis of cytomegalovirus (CMV) retinitis.B, Neovascularization of the iris approximately 1 month after diagnosis of CMV retinitis.C, Diffuse capillary nonperfusion in areas of regressing retinitis approximately 1 month after diagnosis of CMV retinitis.


Nine months after cataract extraction, the patient returned withprofoundly reduced VA due to dense vitreous hemorrhage andrecurrent rubeosis. He underwent pars plana vitrectomy with pos-terior membranectomy and endolaser. The postoperative coursewas complicated by hypotony, nonclearing vitreous hemorrhage,and posterior tractional retinal detachment by ultrasound examina-tion. He underwent repeat vitrectomy with membranectomy andendolaser. His VA increased to his baseline of 20/80, and he iscurrently stable with an attached retina.

Discussion

These cases show the development of retinal non-perfusion and neovascularization in two patients withCMV retinitis, HIV infection, and diminished immunestatus. It is presumed that the CMV retinitis caused theretinal nonperfusion and neovascularization becauseevidence of other possible causes was not found inprevious laboratory studies and physical examina-tions. The retinitis resolved with anti-CMV therapy,providing additional evidence that CMV was the caus-ative agent. Optic nerve head neovascularization hasbeen reported in a patient with inactive CMV retinitisand immune recovery vitritis, without evidence ofcapillary nonperfusion on angiography.4 Our Case 1did have a rise in CD4 count after combination anti-retroviral therapy, but also had evidence of capillarynonperfusion. The immune recovery may have con-tributed to, but may not have been the sole cause of,the development of neovascularization. In Case 2, wecannot rule out the possibility of syphilitic chorioreti-nitis, which has been shown to cause vascularcompromise.5

As in our cases, as the CMV retinitis resolves,atrophy of the retinal vasculature develops. This com-monly occurs as a result of progressive occlusion frommononuclear cellular infiltrates,1 and likely led toischemia and subsequent neovascularization of the irisand retina in these two cases. Atrophic retinal vesselshave been documented in prior cases of CMV retinitiswith both fluorescein angiography and direct his-topathologic examination.6

It is possible that the obliterative effect on arteriolesby CMV infection is potentiated by background HIVmicroangiopathy. Neovascularization has not been re-ported to result solely from the microvascular abnormal-ities seen in background HIV retinopathy.6 Central andbranch retinal vein occlusion have been reported in pa-tients with AIDS and no other known risk factors forvenous occlusive disease.7 The etiology of these vaso-occlusive changes in patients with HIV is unclear.

These cases demonstrate that neovascularizationand the complications associated with neovasculariza-tion are possible in the setting of CMV retinitis andHIV infection. Practitioners should be on guard forthis finding.

References1. Hugh HL, Scott AA, Apple DJ. Cytomegalovirus retinitis.

Surv Ophthalmol 1989;34:193–203.2. Saran BR, Pomilla PV. Retinal vascular nonperfusion and

retinal neovascularization as a consequence of cytomegalovi-rus retinitis and cryptococcal choroiditis. Retina 1996;16:510–512.

3. Conway MD, Tong P, Olk RJ. Branch retinal artery occlusioncombined with branch retinal vein occlusion and optic diskneovascularization associated with HIV and CMV retinitis. IntOphthalmol 1996;19:249–252.

4. Sanislo SR, Lowder CY, Kaiser PK. Optic nerve head neo-vascularization in a patient with inactive cytomegalovirus ret-initis and immune recovery. Am J Ophthalmol 1998;126:318–320.

5. Regan CD, Foster CS. Retinal vascular diseases: clinical pre-sentation and diagnosis. Int Ophthalmol Clin 1986;26:25–53.

6. Newsome DA. Microvascular aspects of acquired immunedeficiency syndrome retinopathy. Am J Ophthalmol 1984;98:590–601.

7. Friedman SM, Margo CE. Bilateral central retinal vein occlu-sions in a patient with acquired immunodeficiency syndrome.Arch Ophthalmol 1995;113:1184–1188.

RETINAL AND CHOROIDAL VASCULARCHANGES IN HETEROZYGOUS FABRYDISEASE

MARCOS A. DANTAS, MD,ROBERTO A. FONSECA, MD,TATSUSHI KAGA, MD,LAWRENCE A. YANNUZZI, MD,RICHARD F. SPAIDE, MD

From the LuEsther T. Mertz Retina Research Center,Manhattan Eye, Ear, and Throat Hospital, and Vitreous-Retina-Macula Consultants of New York, New York.

Fabry disease (angiokeratoma corporis diffusum uni-versale) is an X-linked lysosomal storage disease re-sulting in defective activity of the enzyme lysosomalhydrolasea-galactosidase A.1 This defect leads to aprogressive accumulation of the glycosphingolipid tri-hexosylceramide, especially in the liver, heart, spleen,kidney, cornea, plasma, polymorphonuclear cells, vas-cular endothelial cells, and smooth muscle cells.1,2

The a-galactosidase A locus has been mapped toXq21.33. The diagnosis of the condition can be con-firmed by the finding of decreased levels ofa-galac-tosidase A in the plasma or in polymorphonuclearleukocytes.2

The authors have no proprietary interest in any aspect of thisarticle.

Reprint requests: Richard F Spaide, MD, 519 East 72nd Street,Suite 203, New York, NY 10021.

87BRIEF REPORTS

Patients with typical Fabry disease usually presentwith severe manifestations such as painful acropares-thesia, neurologic abnormalities, cardiovascular dis-ease, heavy proteinuria, and characteristic cutaneousangiokeratomas.1,2 They demonstrate progressive im-pairment of the kidneys, heart, and central nervoussystem, and usually die by the fifth decade of life.2

The ocular findings include whorl-like corneal opacities(cornea verticillata), dilated aneurysmal conjunctivalvessels (corkscrew-like appearance), retinal vessel tortu-osity, granular anterior capsular or subcapsular lensdeposits, posterior capsular cataracts, anterior ischemicoptic neuropathy, and optic disk, retinal, and periorbitaledema.1 The retinal involvement includes dilated veins,but arterial and venous occlusions have also beenobserved.2,3

We describe a female carrier with Fabry disease witha history of central retinal venous occlusion (CRVO) inone eye and unsuspected retinal microvascular and cho-roidal vascular abnormalities in the fellow eye.

Case Report

A 66-year-old white woman was an enzymatically documentedFabry disease carrier with a history of mild episodes of pain anddiscomfort in the limbs (acroparesthesia) during childhood. Hermedical history was negative for systemic arterial hypertension,

diabetes mellitus, systemic lupus erythematosus, past radiationtreatment, or other diseases. Recent cardiac and renal evaluationswere normal. She was asymptomatic in the right eye and had ahistory of a CRVO in the left eye 8 years previously, treated withpanretinal photocoagulation.

Her visual acuity was 20/25 in the right eye and 20/800 in theleft eye. She was myopic, with21.0 diopter in the right eye and21.25 diopters in the left eye. Intraocular pressure was 13 mmHgin the right eye and 12 mmHg in the left. Slit-lamp examinationrevealed characteristic bilateral whorl-like corneal deposits. Tortu-osity (corkscrew-like) was seen in the conjunctival vessels in botheyes. Lens opacities were not seen. Fundus examination of the righteye revealed telangiectatic vessels, occasional microaneurysms,and edema at the temporal macula. The left eye showed panretinalphotocoagulation scars and evidence of old vitreous hemorrhageswith resolving devitalized blood in the inferior vitreous. Fluores-cein fundus angiography (FA) showed areas of nonperfusion, cap-illary telangiectasias, and occasional microaneurysms in the righteye (Figure 1A) and findings of a past central vein occlusion in theleft eye. Later in the course of the angiographic evaluation, therewas diffuse leakage evident in the temporal macula of the right eye(Figure 1, B and C). An indocyanine green angiogram (ICG) wasperformed, and the choroid had a moth-eaten appearance withareas of nonperfusion, gaps in the continuity of the vessels, andlooping of choroidal vessels (Figure 1D).

Discussion

We describe a 66-year-old female carrier withFabry disease who had a CRVO in one eye and

Fig. 1. Right eye.A, Fluorescein angiography shows areas of capillary nonperfusion (large darkarrow), capillary telangiectasias (small dark arrow), and microaneurysms (white arrow).B, Earlyphase fluorescein angiography shows leakage of dye in the temporal macula.C, Late phasefluorescein angiogram shows diffuse leakage of dye in the temporal macula.D, Indocyanine greenangiography shows a moth-eaten appearance with areas of choroidal nonperfusion (large darkarrow), gaps in the continuity of vessels (small dark arrow), and looping of choroidal vessels(white arrow).


unsuspected vascular abnormalities in the fellow eye:regions of capillary nonperfusion and telangiectasias,a few microaneurysms, and leakage of dye during FA,all signs of microvascular damage. During ICG, therewas a moth-eaten appearance and suggestion of cho-roidal vascular perfusion abnormalities.

Males with Fabry disease are at risk for vascularocclusion because they are hemizygous gene carriers.3

Of interest is that females, although they carry anormal X-chromosome, are also at risk for vascularocclusion, especially in the kidneys, central nervoussystem, heart, and extremities.2,3 The reason lies inthe Lyon hypothesis: there is an inactivation of one ofthe X chromosomes in each cell of the female hetero-zygote.3 Inactivation of the normal X chromosomewould leave the cell with only the production ofabnormala-galactosidase with the eventual expres-sion of the gene.3

Studies have been conducted to try to establish themolecular basis of the alterations that are responsiblefor the higher incidence of thrombotic events in pa-tients with Fabry disease.4,5 The concentrations ofsoluble intercellular adhesion molecule–1, vascularcell adhesion molecule–1, P-selectin, plasminogen ac-tivator inhibitor, and platelet aggregation were signif-icantly higher, and thrombomodulin was significantlylower, in Fabry patients.4,5 Expression of the integrinCD11b on monocytes was also significantly higher.4

All of these changes are consistent with a prothrom-botic state and are indicative of endothelial cell leukocyteand platelet activation in these patients. Accumulation ofglycosphingolipids in the vascular endothelial cellsalso may reduce the luminal diameter of the vessels,which may predispose to vascular occlusions as well.4

Although most patients with CRVO have no recog-nizable cause for developing venous thrombosis, theexistence of a prothrombotic state in Fabry disease,and the absence of established CRVO risk factors inour patient (her age was 58 years when the event oc-curred), suggest the possibility that Fabry disease may beimplicated in the occlusive event in her left eye.6

Whereas most reports on retinal changes in Fabrydisease highlight the involvement of the larger vascu-lature, we show a case of retinal microvascular andchoroidal vascular changes in an otherwise healthywoman with Fabry disease. The lack of choroidal andretinal pigment epithelial pigmentary changes, such asseen in Elschnig spots, may be due to the small size ofthe affected vessels, as well as compensatory remod-eling of the surrounding vessels in the choroid. Wecould not attribute the choroidal changes to any otherspecific condition, such as past radiation therapy, andbelieve they may be related to Fabry disease.

Ruling out other diseases that could be responsible

for some of the clinical findings in this patient sug-gests that Fabry disease may affect the choroidal vas-culature and the retinal microcirculation, in addition tothe damage to the larger vessels described else-where.1–3 These findings might occur in carriers whomay present signs and symptoms usually expected tobe found in hemizygotes. Further investigation ofother patients with Fabry disease is needed to inves-tigate the prevalence of microvascular disease. How-ever, it is possible that Fabry disease may be consid-ered in the differential diagnosis of diseases causingboth large and small vessel disease in the fundus.

References1. Sher NA, Letson RD, Desnick RJ. The ocular manifestations

in Fabry’s disease. Arch Ophthalmol 1979;97:671–676.2. Oto S, Kart H, Kadayifçilar S, et al. Retinal vein occlusion in

a woman with heterozygous Fabry’s disease. Eur J Ophthalmol1998;8:265–267.

3. Utsumi K, Yamamoto N, Kase R, et al. High incidence ofthrombosis in Fabry’s disease. Intern Med 1997;36:327–329.

4. Degraba T, Azhar S, Dignat-George F, et al. Profile of endo-thelial and leukocyte activation in Fabry patients. Ann Neurol2000;47:229–233.

5. Igarashi T, Sakuraba H, Suzuki Y. Activation of platelet func-tion in Fabry’s disease. Am J Hematol 1986;22:63–67.

6. The Central Retinal Vein Occlusion Study Group. Naturalhistory and clinical management of central retinal vein occlu-sion. Arch Ophthalmol 1997;115:486–491.

A CASE OF ALPORT’S SYNDROME ANDRETINAL DEGENERATION

EKATERINI TSILOU, MD,BENJAMIN I. RUBIN, MD,RAFAEL C. CARUSO, MD,MURIEL KAISER–KUPFER, MD

From the Ophthalmic Genetics and Visual FunctionBranch, National Eye Institute, National Institutes ofHealth, Bethesda, Maryland.

Alport’s syndrome is the prototype of basementmembrane disease characterized by a structural defectof the noncollagenous portion of type IV collagen.Eighty-five percent of patients show X-linked inheri-tance but autosomal recessive and dominant formsalso have been described. The X-linked and autosomal

The authors have no proprietary interests.Reprint requests: Ekaterini Tsilou, MD, Ophthalmic Genetics

and Visual Function Branch, National Eye Institute, National In-stitutes of Health, 10 Center Drive, MSC-1860, Building 10, Room10N226, Bethesda, MD 20892; e-mail: [email protected]

89BRIEF REPORTS

recessive forms have in common renal, audiologic,and ophthalmologic manifestations. Fleck and dotretinopathy, anterior lenticonus, and posterior polymor-phous-like dystrophy of the cornea are the most commoneye manifestations. Several other ocular manifestationshave been described but not seen uniformly. Ocularabnormalities have not clearly been described in the rareautosomal dominant form.

The purpose of this report is to present a patientwith Alport’s syndrome and evidence of moderatelysevere retinal degeneration.

Case Report

A 35-year-old man with Alport’s syndrome was initially seen inour eye clinic in April 1997. Family history included a sister whohad died at age 33 years from renal failure secondary to Alport’ssyndrome. Ophthalmic history revealed an amblyopic left eye sincechildhood and anterior lenticonus diagnosed at the age of 26 years,followed by bilateral cataract extraction. On examination, best-corrected visual acuity was 20/25 in the right eye, 20/50 in the lefteye. Slit-lamp biomicroscopy revealed multiple endothelial cornealopacities. Ophthalmoscopy revealed yellow punctate lesions in theretinal pigment epithelium (RPE) level of both eyes that spared themacula. Pigment accumulation was seen in both retinas inferiorlyto the vascular arcades. Decreased foveal reflex was noted in bothmaculae as well as patchy hypopigmentation of the RPE in theinferior portion of the right macula (Figure 1). The patient under-went a kidney transplant in July 1997. On follow-up examinationapproximately 2 years later, the ocular examination was un-

changed. Fluorescein angiography (FA) demonstrated bilateralmultiple RPE window defects. Electroretinography (ERG) re-vealed a moderately severe reduction of rod responses (their am-plitude was 20% and 22% of the median normal value in the rightand left eye, respectively) and cone responses (35% and 31% of themedian normal amplitude in the right and lefteye, respectively)(Figure 2). Both a-wave and b-wave amplitudes were reduced to asimilar degree, suggesting that the ERG abnormalities were due toa compromise of photoreceptor function. Electro-oculography(EOG) showed a decline in light peak amplitude with a similardegree of severity as that seen in the ERG (32% and 38% of themedian normal amplitude in the right and left eye, respectively). Inconsequence, the Arden ratio was reduced (1.49 and 1.45 in theright and left eye, respectively).

Discussion

Electroretinography and EOG in Alport’s syndromehave not been studied extensively, with most of thereported cases being normal. In 1974, Hochgesand etal1 reported three patients with Alport’s syndromewith normal ERG and abnormal EOG. This led to theassumption that the origin of the retinopathy was inthe pigment epithelium. In 1980, Perrin et al2 reportedone patient with an abnormal ERG and EOG andnormal FA without any further information. In 1980,Zylbermann et al3 reported two siblings with Alport’ssyndrome having pigment epithelial changes, de-creased ERG, and normal EOG. In 1988, Gelisken et

Fig. 1. The posterior poles ofthe right fundus (A, B) andthe left fundus (C, D) showevidence of punctate retinalpigment epithelial changes(arrows). A depigmented le-sion below the macula (A)and an area of pigment accu-mulation below the inferiorarcade (B) are evident in theright eye.


al4 reported one patient with Alport’s syndrome, saltand pepperlike retinopathy, diminished scotopic ERG,and an elevated threshold on dark adaptation, raisingthe question of a possible associated retinal degener-ation. The EOG was normal. Setala et al5 reported amother and a son with macular degeneration and de-creased ERG.

To our knowledge, our case is the first reporting thedetails of an abnormal ERG and EOG. In addition, anabnormal FA demonstrated window defects in theRPE. In the remainder of the cited cases it was eitherthe ERG or the EOG that was abnormal and the otherparameter was either normal or not reported. Perrin etal2 briefly mentioned that one of their patients hadabnormal ERG and EOG without giving any furtherinformation or reaching any conclusions.

Our patient showed equally diminished cone androd responses as well as EOG changes, pointing to aretinal degeneration with generalized involvement ofthe photoreceptors. The photoreceptor degeneration

could be primary, but is more likely secondary to RPEdegeneration as suggested by the FA.

Alport’s syndrome is caused by a structural defectof collagen type IV that only manifests itself in thekidney, ear, and eye. Although the pathogenesis ofAlport’s retinopathy remains speculative, collagentype IV is a constituent of all basement membranes,including Bruch’s membrane, the basement mem-brane of the RPE.

Long-term follow-up of our patient and other similarcases will be required to further investigate the etiologyand natural history of this retinal degeneration.

References1. Hochgesand P, Steinbach PO, Straub E. Augenveranderungen

bei Alport-Syndrome. Klin Monatsbl Augenheilkd 1974;165:447–452.

2. Perrin D, Jungers P, Grunfeld JP, et al. Perimacular changes inAlport’s syndrome. Clin Nephrol 1980;13:163–167.

3. Zylbermann R, Silverstone BZ, Brandes E, Drukker A. Retinal

Fig. 2. Rod responses (A), maximal responses (B), cone responses (C), and flicker electroretinogram (D) of our patient compared with a normal control.

91BRIEF REPORTS

lesions in Alport’s syndrome. J Pediatr Ophthalmol Strabismus1980;17:255–260.

4. Gelisken O, Hendrikse F, Schroder C, Berden JHM. Retinalabnormalities in Alport’s syndrome. Acta Ophthalmol 1988;66:713–717.

5. Setala K, Ruusuvaara P. Alport syndrome with hereditarymacular degeneration. Acta Ophthalmol 1989;67:409–414.

Correspondence

Early Versus Late Removal of RetainedIntraocular Foreign Bodies

Dear Editor:We appreciated the article on early versus late re-

moval of retained intraocular foreign bodies (IOFB),1

especially concerning the suggested timing for surgi-cal management of retained IOFB. Early removal bypars plana vitrectomy (PPV) reduces the risks of endoph-thalmitis and proliferative vitreoretinopathy (PVR)whereas late removal, despite the risk of endoph-thalmitis and PVR, offers a clean operating field be-cause of the developing posterior vitreous detachmentand reabsorption of hemorrhages. Consequently, Jo-nas and Budde suggest operating as soon as possible.

We found fault with their article because they didnot focus their analysis on a single type of IOFB. Infact, nonmetallic IOFB are associated with a higherrisk of endophthalmitis. Moreover, nonmetallic IOFBwere found only in the group that underwent deferredPPV (two patients). Authors found a higher risk ofendophthalmitis in patients with deferred PPV (P ,0.05, chi square test) but did not consider this anom-alous distribution of IOFB. Ozdamar et al2 show thatsilicone oil can reduce the risk of endophthalmitis, butno patient with this complication underwent siliconeoil tamponade. The better visual outcomes found inthe early removal group did not consider the centralcorneal laceration found especially in the deferredremoval group. Lens cataract, although well distrib-uted in the groups, had to be considered based on thepresence of nuclear fragments in the posterior camber.Those fragments could influence the higher incidenceof PVR found in the deferred removal group.

Following the study of Jonas and Budde, we studiedthe correct timing for removal of retained IOFB. FromJanuary 1996 to December 1998, we treated 273 pa-tients with retained IOFB in our department. Retro-spectively, we selected 29 patients (29 eyes) withscleral open-globe injuries due to metallic and mag-netic IOFB embedded on the retina. In the first group(17 eyes), IOFB were removed within 24 hours (mean

7 hours [SD 1.41]); in 5 eyes, IOFB were found withinthe temporal vascular branches (central IOFB). In thesecond group, composed of 12 eyes (4 with centralIOFB), IOFB were removed after 24 hours (mean 5.75days [SD 5.68]). There was no significative differencebetween the study groups. All eyes underwent three-way PPV and were endotamponaded with silicone oil.We considered anatomic and functional findings atadmission and at 1 week; 1, 2, and 6 months; and 1and 2 years postoperation. We considered the numberof surgical procedures. All patients had retinal reat-tachment. Visual acuity did not vary significantly be-tween the groups during the follow-up (unpairedt-test,P .. 0.05).3 The number of operations was notsignificantly distributed in the groups. Because ofretinal side impact, visual function was seriously com-promised.4 Proliferative vitreoretinopathy was well-controlled with silicone oil and PPV. We found nofunctional or anatomic differences among the groups,showing that early removal has the same prognosticresults as deferred surgery.

Tommaso Micelli Ferrari, MDNicola Cardascia, MD

Ilaria Di Gesu, MDNatalia Catella, MD

Nicola Recchimurzo, MDFrancesco Boscia, MD

Department of Ophthalmology andOtorhinolaryngology

University of BariBari, Italy

Reply

Dear Editor:We appreciate the letter of Dr. Ferrari and col-

leagues, in which they describe their clinical experi-ence with the timing of PPV to remove retained IOFB.We agree that the composition of the foreign body isone of the main risk factors for the development ofposttraumatic infectious endophthalmitis. In ourstudy,1 the IOFB was magnetic in all patients in theearly intervention group and in 17 of the 19 patients(89.5%) in the late intervention group. This differencewas not statistically significant. Frequencies of post-operative infectious endophthalmitis and PVR weresignificantly (P , 0.05) higher in the late interventiongroup than in the early intervention group.

In view of the limitations of the study pointed byDr. Ferrari and colleagues, we continued the investi-gation. In a larger scaled follow-up study,5 the resultsconcerning the risk factors for the development ofpostoperative infectious endophthalmitis were con-


firmed. A total of 130 patients presenting consecu-tively with penetrating ocular injuries due to lacera-tions by foreign bodies were operated on by one oftwo surgeons between 1989 and 1997. Follow-up timewas an average of 20.846 20.76 months. All foreignbodies were located posterior to the lens. Occurrenceof posttraumatic infectious endophthalmitis, develop-ing in seven patients, was significantly (P 5 0.026)associated with removal of the foreign body later than24 hours after the accident and with the type of foreignbody (P , 0.01). Size of the foreign body (P 5 0.37),preoperative visual acuity (P 5 0.62), presence oftraumatic cataract (P 5 0.75) or a retinal lesion by theforeign body (P 5 0.16), age (P 5 0.39), and gender(P 5 0.46) did not show a statistically significantinfluence on the occurrence of endophthalmitis. Sta-tistically significant risk factors for the developmentof PVR, occurring in 27 patients (27/99 [27.6%] pa-tients with a minimal follow-up of 3 months), weresize of the foreign body (P , 0.001), preoperativevisual acuity (P 5 0.02), presence of a retinal lesion(P 5 0.002), and traumatic cataract (P 5 0.03). Thetime between foreign body removal and the accidentwas marginally associated with the development ofPVR (P 5 0.07). It was concluded that prognosis inopen-globe injuries with intraocular or retrobulbar for-eign bodies depends on the size and type of the foreignbody, presence and location of retinal lacerations,additional involvement of other intraocular structures,preoperative visual acuity, and timing of surgery.

In conclusion, the larger-scaled follow-up studyinvolving 130 patients confirms the previous study’sfinding that, in special clinical situations, early re-moval of a foreign body can be beneficial in terms ofreducing the risk of postoperative infectious endoph-thalmitis. The question remains whether early versuslate removal of IOFB also reduces the risk of PVR.

Jost B. JonasDepartment of OphthalmologyFriedrich-Alexander-University

Erlangen, Germany

References1. Jonas JB, Budde WM. Early versus late removal of retained

intraocular foreign bodies. Retina 1999;19:193–197.2. Ozdamar A, Aras C, Ozturk R, Akin E, Karacorlu M, Ercikan C.

In vitro antimicrobial activity of silicone oil against endoph-thalmitis-causing agents. Retina 1999;19:122–126.

3. Pavlovic S, Schmidt KG, Tomic Z, Dzinic M. Management ofintraocular foreign bodies impacting or embedded in the retina.Aust NZJ Ophthalmol 1998;26:241–246.

4. Chiquet C, Zech JC, Denis P, Adeleine P, Trepsat C. Intraocularforeign bodies. Factors influencing final visual outcome. ActaOphthalmol Scand 1999;77:321–325.

5. Jonas JB, Knorr HLJ, Budde WM. Prognostic factors in ocularinjuries due to intraocular or retrobulbar foreign bodies. Oph-thalmology 2000;107:823–828.

Fungal Endophthalmitis After a SingleIntravenous Administration of Presumably

Contaminated Dextrose Infusion Fluid

Dear Editor:We read “Fungal Endophthalmitis After a Single

Intravenous Administration of Presumably Contami-nated Dextrose Infusion Fluid,” by Gupta and cowork-ers, with interrest and concern.1 It is alarming that 11of 72 factory-sealed bottles of 5% dextrose availableto physicians in pharmacies in similar settings showedgrowth of fungus. We have also encountered threepatients who had endogenous endophthalmitis follow-ing a history of intravenous (IV) infusions in a seriesof 14 patients with endogenous endophthalmitis (un-published study). We have observed that such con-tamination occurs if the infusion bottle has a minorcrack during transport. Such cracks may not be visibleand may not leak. Thus, they can be overlooked by thepractitioner during administration of IV infusion.Close inspection can identify such cracks in the bottle.Such cracks can lead to the loss of vacuum maintainedin the bottle allowing the entry of organisms.

Due to the threat of contaminated IV infusion, wehave adopted three simple precautionary measures.

1) Each infusion bottle should be shaken and thenviewed against a pencil of light—e.g., a tablelamp—to look for suspended impurities. We haveseen such particles that subsequently microbiologi-cally tested positive for fungus. This test appears to berelatively simple, but can detect gross contaminationwith fungus.

2) We give a firm thud on the bottom of the glassbottle containing IV infusion fluid with the palm of thehand. In an intact bottle in which vacuum has beenmaintained, a dull thump sound is heard. Such soundis absent in bottles that have lost vacuum due toinvisible cracks.

3) While introducing the needle into the bottle as anair vent, a gurgling sound is heard as air bubbles rushinside the bottle of infusion fluid where vacuum ismaintained. Cracks or leaks can lead to the loss ofvacuum and such sound will be absent. This indicatesthat vacuum is lost and may indicate possible entry oforganism. Such bottles should be discarded.

We also believe that glass bottles, which are com-

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monly used for IV infusion, even though of medicalgrade quality, have more risk of developing cracks.Plastic bottles for infusion can have a much lesser riskof development of such cracks or leaks leading tocontamination and should be preferred.

Such simple precautionary measures can greatlyreduce the risk of infusion-related fungal infectionsincluding endogenous fungal endophthalmitis as re-ported by Gupta and coworkers in rural settings ofdeveloping countries.1

Jyotirmay Biswas, MDMedical and Research Vision Foundation

Chennai, India

Reference1. Gupta A, Gupta V, Dogra MR, et al. Fungal endophthalmitis

after a single intravenous administration of presumably contam-inated dextrose infusion fluid. Retina 2000;20:262–268.

Occurrence of Retinoblastoma and UvealMelanoma in the Same Patient

Dear Editor:We read with interest the article from Wills Eye

Hospital in which the authors reported a patient whounderwent enucleation of her right eye for retinoblas-toma in childhood and then was diagnosed at the ageof 47 years with uveal melanoma in her left eye.1 Theauthors stated that “The probability of occurrence ofunilateral retinoblastoma and then uveal melanoma inthe remaining eye is estimated to be 1 in 165 billion.”

We submit an alternative approach to the likelihoodof such an event. Our goal is to estimate the proba-bility that a single person in America has experiencedboth retinoblastoma and uveal melanoma. To simplifyour computation, we will ignore the impact of bilateraldisease and of mortality from ocular tumors.

First, the prevalence of retinoblastoma is approxi-mately 1 in 15,000 live births. Second, and of greatercomplexity, is the prevalence of uveal melanoma. Thelifetime prevalence of this disease is approximately 1in 2500. Thus, if all living Americans were 76 yearsold (the average life expectancy at birth), approxi-mately 1 in 2500 would have had uveal melanoma. Tosimplify, we will assume that the lifetimes of Ameri-cans are linearly distributed between age 0 and 76years, and that over this range of years the prevalenceincreases linearly from a minimum value of 0 to a

maximum value of 1 in 2500. These approximationssuggest that the “average” prevalence of uveal mela-noma among all living Americans is half of the rate atage 76; i.e., 1 in 5000. Given the additional assump-tion that the prevalence of each tumor is independent,the likelihood that a random American has had bothretinoblastoma and uveal melanoma is:

~1/15,000! 3 ~1/5000! 5 1.333 1028

5 0.0000000133

Conversely, the likelihood that a random Americanhasnot suffered these tumors is 12 0.000000013350.9999999867. To determine the likelihood thatnoliving American has had these tumors, we raise thisfraction to the appropriate power (the approximatecurrent population of the United States):

~0.9999999867!1263,000,0005 0.03026

Thus, these calculations suggest that there is onlyapproximately a 3% chance that no single livingAmerican has had both retinoblastoma and uveal mel-anoma. Even if our assumptions have introduced a10-fold error, there is still greater than a 50% chancethat both retinoblastoma and uveal melanoma haveoccurred in at least one American. Furthermore, suchan American would almost certainly end up eventuallyat the Oncology Service of Wills Eye Hospital.

We conclude that the occurrence of a single Amer-ican with both retinoblastoma and uveal melanomadoes not imply a biologic association between thesetumors.

John GamelProfessor of Ophthalmology

University of LouisvilleLouisville, Kentucky

Reply

Dear Editor:We are grateful to Dr. Gamel for his interest and

response to our article.1 Dr. Gamel has used differentmethodology, prevalence estimates, and assumptionsin calculating the odds of retinoblastoma and uvealmelanoma occurring in the same patient. Fortunately,he arrived at a similar conclusion that the occurrenceof retinoblastoma and uveal melanoma in the same


patient is a rare event with no suggestion for biologicassociation between these tumors.

Arun D. Singh, MDCarol L. Shields, MDJerry A. Shields, MD

Oncology ServiceWills Eye Hospital

Thomas Jefferson UniversityPhiladelphia, Pennsylvania

Paul Sternberg, Jr., MDEmory University Eye Center

Atlanta, Georgia

Reference1. Singh AD, Shields CL, Shields JA, Sternberg Jr P. Occurrence

of retinoblastoma and uveal melanoma in the same patient.Retina 2000;20:305–306.

Errata

Coats’ Response in Leber’s CongenitalAmaurosis

Bhagat, Caputo, Pignato, and Zarbin reported a caseof Coats’ response in Leber’s congenital amaurosis(Retina1999;19:356–359). Although the authors andreviewers believed that this was an original observa-tion, a similar case has been reported by J. Donald M.Gass inStereoscopic Atlas of Macular Diseases,4thEdition. St. Louis: Mosby, 1997:362–363.

Multiple Recurrences of Exudative RetinalDetachment in a Patient with

Vogt–Koyanagi–Harada Disease

In the article “Multiple Recurrences of ExudativeRetinal Detachment in a Patient with Vogt–Koyanagi–Harada Disease” (Retina2000;20:672–674), the cor-responding author’s name was misspelled. The correctspelling is Debra A. Goldstein.

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