Advanced Vitreoretinal Techniques and Technology

EyeWorld reports from the 2010 Asia Pacific Vitreo-Retina Society Meeting in SingaporeSupplement to EyeWorld Asia-Pacific

MIVS with the CONSTELLATION® Vision System

Converting to MIVSMicro-incision vitreoretinal surgery(MIVS) has obvious advantages: greatercomfort for the patient, a more cosmeti-cally appealing result, faster surgery re-quiring no sutures, and a smallersclerotomy that is easier to close.

A few years ago, Sjakon Tahija,M.D., director, Klinik Mata Nusantara,Jakarta, Indonesia, began using the ACCURUS® Surgical System (Alcon, FortWorth, Texas/Hünenberg, Switzerland)for MIVS. With the previous 25-gaugesystem, he found the fluid flow was “notthat good.” For instance, he struggledwith cases of proliferative diabeticretinopathy (PDR), saying it was “achore” getting through thick fibroticmembranes.

At that time he settled on the 23-gauge system to meet his clinical needs.

With the CONSTELLATION® VisionSystem and the new 25+ gauge vitrec-tomy probes, the enhancements havecompletely changed his preference. Hewas amazed by how the change in de-sign and port location has improved thesystem’s fluid dynamics, and he beganusing the system for most cases. Lookingat 45 eyes operated on with the oldersystem around June 2008 and the CONSTELLATION® recently in June2010, he found results of better visualacuity in 41 eyes.

His satisfaction with the ACCURUS®Surgical System might lead one to won-der why he would bother to convert toanother machine. Yet, in the last fewmonths, Dr. Tahija has been using the CONSTELLATION® Vision System.

The CONSTELLATION® cuts at5,000 cpm (the ACCURUS® is optimizedat 2,500 cpm with any gauge probe),and the new system provides even betterfluidics and promises a constant IOP,maintained within a range of +/–2 mmHg. Additionally, the system is capableof injecting silicone oil and is integratedwith an OZil® torsional handpiece(Alcon).

In the end, it is the machine’s per-formance in the clinic that matters, and for Dr. Tahija, it did not disappoint.

Phaco procedures with the CONSTELLA-TION®, he said, while not having OZil®as with INFINITI® (Alcon), are “goodenough,” even allowing him to dealwith hard cataracts—albeit with a littlemore patience and higher parameters.

With the CONSTELLATION®, saidDr. Tahija, “I can deal with anythingthat comes through the door.”

Moreover, Dr. Tahija finds the ULTRAVIT® vitrectomy probe “fantas-tic.” The 25+ vitrectomy probe “actuallyworks just as well or even better thanthe 23-gauge probe,” he said, removingfibrosis next to blood vessels with gentleease.

In one case of proliferative diabeticretinopathy, Dr. Tahija was able to im-prove the patient’s vision from handmovement to 0.2.

The system also features duty cyclecontrol, which allows the surgeon toshift between core and shave vitrectomy.Dr. Tahija recommended adjusting thevacuum and holding cut rate constant.Thanks to the system’s excellent fluidics,helped in part by the high cut rate, theIOP remains constant “no matter whatthe vacuum”—even at rates highenough to aspirate silicone oil.

Enhanced visualization in MIVSWhile the CONSTELLATION® repre-sents a “new revolution,” allowing su-tureless surgery with a 25-gauge probe,minimizing the risk of wound leak and

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“ Be thorough with eachstep of any procedure andoptimize visualization withproper illumination and the use of dyes whenevernecessary”Doric Wong, M.B.B.S.

On November 18,2010, a panel ofvitreoretinal ex-

perts gathered to-gether at the MarinaBay Sands Expo &Convention Centre in Singapore for an in-depth discussion ofAdvanced VitreoretinalTechniques and Technology (AVTT). The meet-ing brought into focus technology that has“come into fruition” since the last AVTT held inHong Kong in 2008, said moderator Ong SzeGuan, M.B.B.S., F.A.M.S., Singapore NationalEye Centre (SNEC).

The panel comprised a group of “earlyadopters,” a “constellation of stars,” said Dr.Ong, who are among the first to integrate newtechniques and technology into their practice.There is a need, he said, to “push this facet ofvitreoretinal surgery” and bring it to “a higherlevel of discussion.” The members of the panelshared their personal experiences with an audi-ence of vitreoretinal specialists from all overthe Asia-Pacific region, adding some useful tipsfor making the most of the exciting new toolsat their disposal.

Contact informationOng: +65-6322-8346,Ong_Sze_Guan@snec.com.sg

ModeratorOng Sze Guan, M.B.B.S., F.A.M.S.Singapore

PanelSjakon Tahija, M.D.Jakarta, Indonesia

I Van Ho, M.B.B.S., M.P.H., Ph.D.Sydney, Australia

Peter Kaiser, M.D.Cleveland, Ohio

Manish Nagpal, M.B.B.S., M.S.Ahmedibad, India

Doric Wong, M.B.B.S., M.Med(Ophth)Singapore

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hypotony, I Van Ho, M.B.B.S., M.P.H.,Ph.D., vitreoretinal surgeon, RetinalUnit, and director, Vitreoretinal Fellow-ship, Sydney Eye Hospital, said that “vi-sualization is the key” to optimal MIVS.

Vitreoretinal surgery, he said, pres-ents several challenges in terms of visu-alizing the surgical field: the confinedspace of the globe, the anatomical inac-cessibility of some structures, and thetransparency of tissues in the eye.

Advancements in lens technologyhave expanded the surgeon’s view fromabout 20 to 60 degrees of visual freedomwithin the eye to a view of the wholeretina using wide-angle lenses. Adju-vants consisting mainly of agents suchas indocyanine green (ICG) and triph-enylmethane dyes allow surgeons to vi-sualize otherwise transparent tissue.Meanwhile, pharmaceutical agents suchas steroids and, in particular, the anti-VEGF agent bevacizumab (Avastin,Genentech, South San Francisco,Calif.)—the “holy water” of retina sur-geons, by the administration of which,said Dr. Ho, “almost all your sins can beforgiven”—can be used to decrease hem-orrhage and clear the surgical field.

None of which, of course, would beany use to the surgeon without properillumination. Without light, said Dr. Ho,you can’t do a thing.

To this end, the CONSTELLATION®includes an advanced Xenon Illumina-tor. The Xenon Illuminator produceswhite light that provides bright illumi-nation that appears almost natural, al-lowing clear tissue resolution andseparation independent of the surgicalmicroscope. In Dr. Ho’s experience, theillumination provided by the Xenon Il-luminator is so good that it allows himto operate more efficiently, reducing sur-gical time and the risk of complications.

In addition, the Xenon light spec-trum cuts off at 440 nanometers, filter-ing out all the blue light. Retinalsurgery, said Dr. Ho, puts the patient’sretina at risk for acute phototoxicityfrom exposure to blue light, adding tothe time pressure on the surgeon. TheXenon Illuminator’s spectrum allows thesurgeon to operate longer when neces-sary without increasing the risk of reti-nal damage.

These characteristics make theXenon Illuminator the safest lightsource currently available, said Dr. Ho.

The last point brings up a furtherconcern for surgeons operating on pa-

tients with maculas already damaged bydisease. Blue light, said Dr. Ho, can alsocause phototoxicity with long-term ex-posure. To this end, Dr. Ho prefers usinga blue-blocking IOL for patients whoalso require cataract surgery.

“I use the Alcon Natural yellow lensbecause I want to reduce the chronic ex-posure to blue light to an already sickretina,” he said.

Transitioning to MIVSSurgeons who want to make the transi-tion to MIVS need to pay close attentionto wound construction; the small caliberof the incision alone isn’t enough to pre-vent wound leak and hypotony.

How you start the surgery, saidPeter Kaiser, M.D., Cole Eye Institute,department of ophthalmology, Cleve-land Clinic, is therefore “vitally impor-tant,” determining as it does the finalwound architecture.

Dr. Kaiser shared three maneuversthat optimize sclerotomy wound con-struction at the start of MIVS: (1) dis-place the conjunctiva; (2) flatten thesclera before inserting the trocar blade;and (3) insert the blade at an angle.

Examining the mechanics of woundconstruction, each of these maneuversmakes sense. The first allows the con-junctiva to act as a kind of natural tam-ponade as it slides back into place overthe wound after surgery is completed,while the second and third create a tun-nel with a long chord length that col-lapses into itself after the instrumentsare withdrawn at the end of surgery.

The efficacy of these maneuvers isborne out by Dr. Kaiser’s experience, butthe evidence supporting their use is notjust anecdotal. Dynamic wound studieshave shown that wounds created with adirect rather than an angled approachgape regardless of ocular pressure. Inparticular, a study by Rizzo, et al. hasshown that the blade should be insertedas obliquely as possible to create an opti-mal, self-sealing wound.

In addition to preventing woundleak and hypotony, optimal wound con-struction using these maneuvers pre-vents the potential ingress of bacteria, asdemonstrated in laboratory tests usingIndia ink (India ink particles are aboutthe size of bacteria) and informal retro-spective analyses of post-vitrectomy en-dophthalmitis rates (the rates appear tobe higher in cases that used a straight/di-rect approach to wound construction).

At the end of surgery, Dr. Kaiser of-fered the following tips: (1) cannulasshould be removed with solid instru-ments inserted into them to prevent vit-reous wick; (2) don’t hesitate to throw astitch when you need to; and (3) pres-sure on the inner lip closes the internallip of the wound.

Closure, he said, is not about speed.The surgeon needs to patiently examinethe incisions and do what is needed toensure that they do not leak and lead tohypotony or, worse, endophthalmitis.

Availability of small-gauge instrumentationThe other paradigm that has shifted theability to use MIVS for most cases is theavailability of small-gauge instrumenta-tion and tools to address more difficultpathologies. Originally, there was a verylimited armamentarium of forceps andscissors to use in 23G and 25G.

Today, the GRIESHABER® Single-Use DSP line (Alcon) offers a wide vari-ety of tools for both fine and heavymembrane pathologies ranging fromILM forceps to MAXGrip forceps withgreater grasping force for heavy tissues.There are also ancillary instruments likescissors, soft tips, backflushes, picks, andspatulas available when they are neces-sary.

Surgeons now have all the toolsthey need to do most if not all cases insmall gauge, according to Dr. Kaiser.Keeping these tips and tools in mind,transitioning to MIVS is, more than any-thing else, really about “just doing it,”Dr. Kaiser said.

Ultra high-speed cutting and port optimizationThe industry has been trying to developfaster cutters for years, said Manish Nagpal, M.B.B.S., M.S., vitreoretinal con-sultant, Retina Foundation, Ahmedabad,India. “The faster you cut, the safer it isbecause the tissue traction is going to bemuch less,” he said.

Older cutters used a spring-based de-sign that would “limit in some form thespeed of the cutting,” said Dr. Nagpal.The CONSTELLATION® Vision System,which Dr. Nagpal has been using forabout a year now, has overcome muchof this problem.

High-speed videos show that, compared with other cutters, the CONSTELLATION’s® cutter port opensfaster, effectively increasing the “opentime” of the port even when the cutters

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Advanced Vitreoretinal Techniques and Technology

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EyeWorld reports from the 2010 Asia Pacific Vitreo-Retina Society Meeting in Singapore

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are operating at the same cut rate. Thisincreased duty cycle enhances the flowthrough the port, maintaining good flu-idics, taking in more tissue with each cutcycle, even when working at high speed.With the older ACCURUS® Surgical Sys-tem, Dr. Nagpal and his colleagues hadto reduce the cut rate to well below max-imum to cut through the same amountof tissue.

In addition, the design of the cutteris so fine that the cutter port’s blade isalmost flush with the shaft; this allowsthe surgeon to cut tissue even when itlies almost flat on the retinal surface. Dr.Nagpal and colleagues have thus beenable to reduce the number of instru-ments—needles, scissors, and othersmall-gauge probes—they need to em-ploy during surgery.

The cutter is so efficient and the flu-idics so excellent that Dr. Nagpal hasbeen able to use it even with multipleinterfaces, when the eye contains sili-cone oil and/or air in addition to fluid.

In one case with a large subretinalneovascular membrane, Dr. Nagpal wasable to use the cutter to “eat up” a largecalcific plaque hidden beneath themembrane.

The biggest advantage of having ahigh cut rate (up to 5,000 cpm) com-bined with efficient fluidics and small,25+ instrumentation, said Dr. Nagpal, isthe safety. In cases with a lot of mobiletissue such as with hemorrhage or withvitreous attached to the retina, “you canalmost control the movement,” he said.

In fact, reducing the cut rate to3,000 actually increases the visible tur-bulence. The CONSTELLATION® Vision

System, said Dr. Nagpal, operates on acompletely different dynamic rangethan previous cutters, such that it is nolonger necessary to adjust the cut rateduring surgery. Leaving the cut rate at aconstant 5,000 cpm, the surgeon needonly adjust the vacuum rate for mostpurposes during vitrectomy.

Challenging casesAdvances in instrumentation tell onlypart of the story; in the end, you stillhave to know what to do with them.

Doric Wong, M.B.B.S., M.Med(Ophth), is senior consultant and headof the Vitreo-Retina Service, SingaporeNational Eye Centre, where vitreoretinalspecialists routinely perform cataractsurgery. In a series of videos, he demon-strated his own techniques in a varietyof cases.

For standard phaco-vitrectomies, Dr.Wong likes to begin with a superior scle-ral incision, which he finds “universallyself-sealing.” He performs a de novophaco first, without inserting the vitrec-tomy cannulas. After completing thephaco part of the procedure, the eye is“quite stable” with the superior scleralincision.

Proceeding with the vitrectomy, Dr.Wong likes to come in through the infe-rior temporal quadrant so that his can-nulas and tubes don’t dangle at awkwardangles while he’s operating.

For the sclerotomy, he inserts theblade at 5 degrees, angling it to 30 de-grees to ensure a self-sealing incision. Heuses dyes to visualize any membranesthat may be present on the retinal sur-face.

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Beyond standard cases, Dr. Wongrecommends that surgeons deal with is-sues and develop their own techniqueson a case-to-case basis. “There are manyways to skin a cat,” he said. For instance,in dealing with a dropped IOL, he hasdeveloped his own technique for pickingup the IOL. After clearing out the vitre-ous and mobilizing the dislocated IOL,he turns up the vacuum without the cut-ter. Using the vitrectomy probe at thesesettings, he floats the IOL up to the levelof the pupil, at which point he can useforceps or a needle to take the IOL out ofthe eye.

In the end, he said, surgeons mustknow what they are capable of achiev-ing. They must know the limitationsand abilities of their equipment, and itdefinitely helps to “keep up with the lat-est toys.”

Dr. Wong recommended being thor-ough with each step of any procedureand optimizing visualization withproper illumination and the use of dyeswhenever necessary.

Finally, he said, “Time is not onyour side,” so surgeons need to be effi-cient. “Don’t panic, but think quicklyon your feet,” he said.

Contact informationHo: +612-941-3333, ivanho1973@hotmail.comKaiser: +216-444-6702, pkkaiser@aol.comNagpal: +079-228655371,drmanishnagpal@yahoo.comTahija: +62-21-5261415, sgtahija@austindo.co.idWong: +65-6322-8804,Doric_Wong@snec.com.sg

“Visualization is key” in optimizing MIVSSource: I Van Ho, M.B.B.S., M.P.H., Ph.D.

Using MIVS, even difficult cases such as this patient with primary PVR can achieveoptimal outcomes Source: Doric Wong, M.B.B.S., M.Med(Ophth)

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This supplement was produced by EyeWorld under an educational grant from Alcon.

Copyright 2011 ASCRS Ophthalmic Corporation. All rights reserved. The views expressed here do not necessarily reflect those of the editor, editorial board, or the publisher, and in no way imply endorsement by EyeWorld, APACRS or ASCRS.

positive results so far in clinical trials.Unfortunately, those same trials

show that to benefit from these drugs,patients need to receive injections everymonth for the rest of their lives. Re-searchers have thus been looking forother ways to attack VEGF.

One drug currently in studies isVEGF Trap (Regeneron Pharmaceuticals,Tarrytown, N.Y.), a fusion protein thatcombines a human Fc fragment withtwo different domains from two VEGFreceptors—receptor 1 and receptor 2. Byworking on these two receptors, VEGFTrap blocks both VEGF and placentalgrowth factor (PlGF), another angiogenicfactor. Studies have shown that VEGFTrap is at least as effective asranibizumab and bevacizumab, but alonger half-life allows it to achieve thesame results with fewer injections.

Meanwhile, in China, KanghongBiotechnology (Chengdu, Sichuan) hasbeen developing a drug similar to VEGFTrap. KH902 also consists of domainsfrom receptors 1 and 2 fused to a humanFc fragment, but includes only one do-main from receptor 2. Early studies havebeen promising: compared with VEGFTrap, KH902 has been shown to havebetter binding activity and a better abil-ity to prevent endothelial cell prolifera-tion. Compared with bevacizumab, oneongoing study has already resulted in a10-letter difference in visual improve-ment between the two drugs just threemonths into the study. Unfortunately,said Dr. Kaiser, the company appears tohave no immediate plans of taking thedrug out of China.

Upstream/downstreamAn alternative approach that researchersare currently exploring is upstreamblockade—blocking the pathway beforeVEGF is produced. There are many possi-ble targets, but all the different pathwaysappear to go through one area: themammalian target of rapamycin(mTOR), which activates HIF-1α. HIF-1α,in turn, activates around 60 differentgenes, downregulating anti-angiogenicfactors while upregulating angiogens.Two mTOR blockers, both rapamycinanalogs, are currently under investiga-tion.

Developments in surgical tech-niques and instrumentation asexemplified by the CONSTELLA-TION® Vision System (Alcon,

Fort Worth, Texas/Hünenberg, Switzer-land) represent only one facet of thefield of vitreoretina. Parallel develop-ments in medical retina have been atleast as exciting and have certainly beenmore diverse, presenting a dizzying arrayof potential medical approaches to thetreatment of conditions such as maculardegeneration, diabetic retinopathy, andvein occlusion.

Over the last few years, Peter Kaiser,M.D., Cole Eye Institute, department ofophthalmology, Cleveland Clinic, hasbeen actively involved in many clinicaltrials examining the potential of just afew of these approaches and has madehimself familiar with the different path-ways currently being explored aroundthe world.

The anti-VEGF “key”The “key” that specialists have exploredis the different ways to block vascularendothelial growth factor (VEGF). Untilrecently, anti-VEGF agents such as pe-gaptanib (Macugen, Pfizer, New York,N.Y.), ranibizumab (Lucentis, Genen-tech, South San Francisco, Calif.), andbevacizumab (Avastin, Genentech) werethought to control angiogenesis. Theseagents have now been found to blockleakage without really affecting angio-genesis.

VEGF has several isoforms; pegap-tanib is an aptamer for only one iso-form—VEGF-165. Ranibizumab andbevacizumab, on the other hand, actnear the binding site of VEGF so thatthey block all isoforms, leading to the

RNA interference, on the otherhand, currently being explored by Pfizer,offers potential blockade even furtherupstream, on the pathway above mTOR.By working so far upstream, the drugcurrently being investigated decreasesangiogens and increases anti-angiogenicfactors. Phase I test results were excel-lent, and the drug is currently in Phase IItrials.

Going back downstream on theVEGF pathway, companies are develop-ing agents that block integrins and in-hibit tyrosine kinase, while otherpathways and targets such as bioactivelipids, nicotinic acetylcholine receptors,and platelet-derived growth factor(PDGF) are also being explored.

At the moment, anti-PDGF is themost exciting for Dr. Kaiser. No otherdrug has so far shown the ability tocause regression of neovascularization instudies; even patients who lost visionwere shown to have neovascular regres-sion on fluorescein angiography withanti-PDGF. The drug is currently inPhase II testing.

Finally, complement inhibition pro-vides the potential to treat macular de-generation. The complement cascade isparticularly implicated in the develop-ment of dry macular degeneration, andmost drugs working in this pathway—and there are many potential targets forcomplement inhibition—are in Phase Itests specifically for dry macular degen-eration. Only one drug is in Phase II test-ing for wet macular degeneration. POT-4(Alcon) acts on C3 and can potentiallytreat both dry and wet macular degener-ation.

Medical retina tomorrowIn the future, Dr. Kaiser expects medicalretina specialists to be much like oncolo-gists, selecting drugs to combine for thetreatment of specific cases. While theremay be an overwhelming array of poten-tial treatments currently being investi-gated, in all probability, only about 10%of the agents under study will actuallymake it to the clinic, highlighting theimportance of ongoing research and theexhaustive exploration of all the possibleavenues for treatment.

Contact informationKaiser: +216-444-6702, pkkaiser@aol.com

EyeWorld reports from the 2010 Asia Pacific Vitreo-Retina Society Meeting in Singapore4

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Medical retina: From today to tomorrow

“ Only about 10% of the agents under study will actually make it to theclinic, highlighting the importance of ongoing research” Peter Kaiser, M.D.

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