The Bestof Retina AAO 2008

A S U P P L E M E N T T O E Y E N E T M A G A Z I N EEyeNet

S E L E C T I O N S

The Best of CATARACT SURGERY

The Best of PRACTICEMANAGEMENT

The Best of REFRACTIVE SURGERY

The Best ofThe Best of RETINARETINA

4 s u p p l e m e n t

EyeNetRETINA SUBSPECIALTY DAY

ATLANTA 2008

S E L E C T I O N S

Charles Bonnet Syndrome: When Visual Loss Conjures MischiefHallucinations may be a problem of the visual system and not of cognitive function.

5

Dry AMD: Hope Is in the PipelineWet AMD has garnered more attention, but that may soonchange.

9

clinical update

13feature

Community Eye M.D.s Tackle the Intravitreal InjectionMany patients may come to rely on their primary ophthalmolo-gist for their AMD therapy.

Diagnosing and Treating HistoplasmosisA thorough look at managing this fungal infection.11

ophthalmic pearls

Prompt and Aggressive Treatment Might Have Preserved This Mechanic’s VisionThis condition could challenge your medical skills.

19morning rounds

Dear Retina Subspecialty Day Attendee, Retinal medicine is in full flower these

days, with new insights into the origins ofmacular degeneration, a deeper under-standing of genetic retinal dystrophiesand fantastic new imaging technologiesthat capture associated pathologies inreal time.

“Vistas and Viewpoints” is the aptlynamed Retina Subspecialty Day at theAtlanta Meeting, and there is an equally

apt method for preparing to get the mostout of your sessions: Spend some timebrowsing through EyeNet Selections, themost relevant stories from one of themost relevant years in your field.

L e t t e r F r o m t h e E d i t o r

Richard P. Mills, MD, MPHChief Medical Editor

EyeNet Magazine/EyeNet Selections

ON THE COVER: RPE alterations, loss of choroidal melanocytes and a resultant sunset-glow fundus, choroidalDalen-Fuchs–like nodules, and subretinal fibrosis bilaterally. Emmett T. Cunningham Jr., MD, PhD, MPH

e y e n e t s e l e c t i o n s 5

Walter J. Burghardt, SJ,can’t see more than handmotion with one eye orcount fingers at three feetwith the other. Yet the 93-

year-old Jesuit scholar and theologian“sees” a country garden. Sometimes heeven sees joggers, rows and rows ofthem, running through the greenery.

Fr. Burghardt, who lives in Philadel-phia, has Charles Bonnet syndrome(CBS), a disorder of visual hallucina-tions that occurs in cognitively normalpersons with severe bilateral visual lossor deafferentation of the visual cortex.In his case, the visual loss is due to neo-vascular macular degeneration, thoughany visual impairment can trigger thehallucinatory visions. The more severethe impairment, the greater the chanceof having the visual aberrations, whichcan last seconds, minutes or hours.

“The hallucinations are often gen-uinely formed and quite vivid,” said EricEggenberger, DO, professor of neurolo-gy and ophthalmology at Michigan StateUniversity. “The patients can tell youminute details about the scenes they’reseeing. It’s almost like a running movie.”

The etiology and the prevalence ofCBS are both ill-defined.

How common? In a review of the lit-erature, Barry W. Rovner, MD, a geri-atric psychiatrist who conducts researchon depression and AMD, found theprevalence of CBS patients attendingophthalmology clinics ranges from 0.4

percent to 14 percent.1

Gary C. Brown, MD, director of theretina service at Wills Eye Institute inPhiladelphia and professor of ophthal-mology at Jefferson Medical College,and Melissa M. Brown, MD, adjunctassistant professor of ophthalmology atthe University of Pennsylvania, wrote apaper not yet in print on CBS with Fr.Burghardt. They report that 59 percentof 100 patients they looked at with neo-vascular AMD saw photopsias in thecentral visual field—whirly colored orwhite lights. Another 12 percent hadformed visual hallucinations, which inFr. Burghardt’s case took the form ofscenery and joggers. Others have reportedseeing flowers, insects, buildings, facesand branching structures.

Etiology UnknownCharles Bonnet, the Swiss naturalistand philosopher who first described the eponymous condition in 1760 afterobserving it in his 87-year-old mentallyalert grandfather, writes that “all of thisappears to have a seat in that part of thebrain involved with sight.”2

A failure to communicate. One cur-rent theory holds that CBS is most oftenrelated to direct damage to the visualsystem. A contrasting theory is that theimages represent release phenomenadue to deafferentation of the visualassociation areas of the cerebral cortex.1

It’s the same idea as phantom limb syn-drome, explained Dr. Rovner, who isprofessor of psychiatry and neurologyat Jefferson Medical College in Philadel-phia. “Why would you feel something

in your leg, when you have no leg?”Yetsome people do. When, for example, thenerve cells that once went to the footand that continue to be represented inthe brain become active, they can leadto the perception that one’s foot is tin-gling.“If you don’t have the normalinput from those nerve cells, then thosenerve cells are free to go off on theirown direction,” Dr. Rovner explained.

Something similar happens with CBShallucinations, Dr. Rovner said. Some-times, when the pathway between theeye and the occipital cortex is interrupt-ed, “those cells or their connections cango haywire, do things on their own,without regard to real stimuli.”

“You’re Not Going Crazy”While seeing things that aren’t theremight sound distressing, most patientsreport their visions in a nonemotionalway.“They’re not distressed,” Dr. Eggen-

Charles Bonnet Syndrome:When Visual Loss Conjures Mischief

R E T I N A

Clinical Updatetools and t echn iques

by miriam karmel, contributing writer

A patient of Dr. Golnik was tormentedby bumblebee hallucinations.

S t u n g b y V i s i o n s

This article originally appeared in the February

2008 issue of EyeNet Magazine.

6 s u p p l e m e n t

berger said. “Patients describe it morein the realm of a nuisance or a distrac-tion, rather than something that’s dri-ving them crazy.”

Still, the experts agree that it’s impor-tant to reassure patients that they aren’t“crazy,” that they don’t have a psychi-atric disorder, but, rather, a recognizedcondition with a name. And since thereis no consistently effective treatment or generally agreed upon treatment forCBS, reassurance is often the best—andperhaps the only—thing a physician cando for patients who are seeing things.

“The first thing I tell patients is, ‘Thisdoes not mean you’re going nuts. This is a well-known phenomenon.’ It’s yourbrain making up vision because youcan’t see anymore,’” said Karl C. Golnik,MD, professor of neuro-ophthalmologyand neurosurgery at the University ofCincinnati and the Cincinnati Eye Insti-tute. After this reassurance, said Dr.Golnik, some patients confess that theywere afraid to mention the hallucina-tions, that they thought they were goingmad, even that they feared their childrenwould put them in a nursing home.

Take the initiative. Because fear can prevent patients from mentioningthe hallucinations, experts say doctorsshould initiate the conversation. “Iwould prefer for physicians, when theyhave people with severe bilateral visualloss, to educate them that this canoccur,” said Dr. Melissa Brown.

Dr. Eggenberger agrees. While it’snot necessary to discuss CBS with everypatient, he advised raising the issue withany patient whose visual acuity is 20/100or 20/200 in both or the best seeing eye.“I couch it in benign terms,” he said,usually by saying, “It is possible thatpeople develop visions when their visionis bad.” Then, rather than the accusato-ry inquiry, “Are you seeing things?” heprefers, “Are your eyes playing tricks onyou?”

Dr. Rovner uses similar phrasing,such as, “Do you ever see anything thatother people don’t see?”

Dr. Gary Brown reassures patientsthat the hallucinations will go away withtime. “Sometimes it can take weeks tomonths. But they do go away.” (See“Mind Over Mirage.”)

Is It CBS or Something Else?Dr. Eggenberger said a diagnosis of CBSrequires ruling out widespread dementiaor some other condition that more glob-ally affects cognition.

To make a diagnosis of CBS, headvises looking for the following:● A normal cognitive exam.● Absence of psychosis.● Normal attention level.● Sufficient visual loss—20/100 or20/200 in both or the best-seeing eye.

Dr. Golnik said that if any of the fol-lowing are observed, it’s probably notCBS:● The patient had poor vision foryears, but only recently had hallucina-tions. CBS typically occurs around thetime of vision loss.● The patient has good vision in eithereye. A diagnosis of CBS requires poorvision in both eyes.● Ophthalmologists think about the

eyes, but the hallucinations may be asignal of something else going on in thebrain. If a patient complains of systemicsymptoms such as numbness, tingling,weakness on one side of the body or anew peripheral visual field defect, con-sider stroke.● If the patient is not aware that it’s ahallucination and really believes his orher eyes, then that’s a red flag.

Treatment OptionsSome patients are extremely botheredby the hallucinations. In that event, med-ication may be an option. (See “Banish-ing Bumblebees.”)

Referral to a low vision specialist is another option. Because the halluci-nations tend to resolve when visionimproves, the patient might benefitfrom instruction in improved lightingor the use of optical devices.

Dr. Melissa Brown aims for preserv-

R e t i n a

Everywhere I look, I’m seeing bumblebees,” a patient told Dr. Golnik. She’dlost vision in both eyes from giant cell arteritis and now “saw” bumblebees.“What am I going to do?” she asked.

While most patients are satisfied with an explanation that their hallucinationsare the result of visual impairment and not a sign of dementia, others want morethan reassurance. “Some patients are extremely tormented by the hallucinations,”said Dr. Rovner. Those patients might benefit from medication, although there areno drugs specifically approved for treating CBS. “We don’t know how to treat itbecause there are no clinical trials,” said Dr. Rovner. “We’re left to an empiricalapproach to treatment.”

Attempts to treat thus far. Since they’re dealing with hallucinations, doctors haveprescribed antipsychotic drugs that ordinarily treat schizophrenia, Dr. Rovner said.Antiseizure agents have also been tried, as well as donepezil, a cholinesteraseinhibitor used for Alzheimer’s disease, and neuroleptic medications, such ashaloperidol or olanzapine.

“It’s all anecdotal,” said Dr. Golnik, who has had mixed results treating CBS withmedication. “It’s not the case that you take medicine X and you will be better.”

As a neuro-ophthalmologist, Dr. Eggenberger feels comfortable prescribing neu-roleptics, a potent class of medications with significant side effects. But he advisedagainst a general ophthalmologist medicating for CBS. He said most of his patientsopt out of pharmacotherapy, preferring to live with the hallucinations than the sideeffects of the drugs.

Dr. Rovner was more emphatic about caution with treatment. “The psychiatristshould be the prescribing physician for antipsychotic medications.”

In the case of the woman who saw bumblebees, Dr. Golnik prescribed trim-ipramine, after she called and told him, “This is driving me crazy. Stop it!”

Trimipramine, a tricyclic antidepressant he had used with success on a differentpatient, helped decrease her symptoms, Dr. Golnik said. “She had a diminution inthe number and what she called ‘intensity’ of the bees.”

Ban i sh ing Bumb lebees


ing quality of life and mental outlook in these patients.“Even if our patientscan’t see well, if we can just let themknow that what they’re seeing is anexpected phenomenon and not a psychiatric event, then they accept it and their quality of life is greatlyenhanced.”

1 Rovner, B. W. Curr Opin Ophthalmol 2006;

6:275–277.

2 Hedges, T. R. Surv Ophthalmol 2007;1:

111–114.

Fr. Burghardt passed away shortly after this

story appeared. We are grateful for his will-

ingness to share his experience with the

ophthalmic community.

Forgoing medication for his hallucina-tions, Fr. Burghardt, who coauthoreda paper on CBS with Drs. Gary andMelissa Brown, took matters into hisown hands, or rather, his own mind.“Several months after my first experi-ence of scenery, I was mulling over aremark made, I believe, by my primaryophthalmologist, Dr. Gary Brown: In hallucinations the brain is givingdirections to the eyes,” writes Fr.Burghardt.

Then he had an inspiration. “I satstraight up: This brain is my brain! . . .I began talking to my brain. Directly,as if person to person, even at timesas friend to friend. Softly, quietly, nodemands. Rather along these lines: ‘I notice your preference for red andwhite. Would you favor me with asmall change? I like blue; it’s thecolor dominating my living room.’ Notmuch later blue began to appear. Withonly rare reminders on my part, bluegradually displaced more and more ofthe red.”

Fr. Burghardt has not been able to eliminate the hallucinations com-pletely, but he is pleased that he cangain some power over them. “Theadventure with color, its unexpectedresults, gave me a certain measure ofconfidence. My brain is aware (at leastsometimes) of what I am thinking,saying, doing.”

M i n d O v e r M i r a g e


The anti-VEGF agents beva-cizumab (Avastin) and ranibiz-umab (Lucentis) have trans-formed the treatment ofneovascular macular degen-

eration. Finally, there is a treatment thatstops the leakage, dries the retina and inmany cases restores normal anatomy.

Still, some patients lose vision. PhilipJ. Rosenfeld, MD, PhD, the doctor whopioneered the use of the Avastin in theeye, wanted to know why. After analyzingdata from the MARINA and ANCHORtrials, he found there was no differencein terms of CNV leakage between thosewho lost and those who gained threelines of vision.

“We expected patients who lostvision to have a greater amount of leak-age from their CNV over time, but thatjust wasn’t the case,” said Dr. Rosenfeld,who is professor of ophthalmology atBascom Palmer Eye Institute. “Itappeared as though we successfullyconverted the wet AMD back to dryAMD. My hypothesis is that patients losevision because their underlying dry mac-ular degeneration continues to progress.”

Dr. Rosenfeld noted that interestremains high in developing new treat-ments for wet AMD, with a focus oncombining therapeutic agents, similar tothe paradigm for cancer chemotherapy.Unlike cancer, in which cells are geneti-cally unstable and are always trying tofind new ways to proliferate, AMD is agenetically stable disease, he explained.

“We don’t expect these drugs to becomeineffective over time because of muta-tions within the macula.”

Dr y Needs WorkNow the attention turns to dry AMD,which ranges from patients with goodvision and drusen to patients with geo-graphic atrophy and visual acuities aspoor as 20/200. Dr. Rosenfeld explainedthat dry AMD, just like any neurodegen-erative disease, represents a challengingsituation. In that regard, “NeovascularAMD was the low-hanging fruit. Nowwe’ve got a very difficult problem inattacking the dry AMD,” he said.

People with dry AMD will welcomethis shift in attention. “Over and overthey’re told, ‘You’re lucky you have dryAMD,’” said Lylas G. Mogk, MD. Yetpatients with dry AMD, whose vision

loss is associated with drusen or geo-graphic atrophy, can have just as manyproblems as patients with CNV, shesaid. Dr. Mogk is director of the VisualRehabilitation and Research Center ofthe Henry Ford Health System in Detroit.In an analysis of 467 patient charts from1999 to 2003—before the anti-VEGFtreatments were in use—Dr. Mogkfound that patients with dry AMD suf-fered as much as those with CNV in mostmeasures, including reading, depression,contrast sensitivity loss and the need forrehabilitation training. “They’re tryingto figure out why they’re lucky,” she said.

The neglected thief of vision. Janet S. Sunness, MD, medical director of theRehabilitation Services for Low Visionand Blindness at the Greater BaltimoreMedical Center, agreed that there’snothing lucky about having advanced

Dry AMD:Hope Is in the Pipeline

R E T I N A

Clinical Updatetools and t echn iques

by miriam karmel, contributing writer

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Macular perimetry with a scanning laser ophthalmoscope shows a dense ring sco-toma (DS) surrounding central fixation (in red) which is interrupted by a secondtiny scotoma (1). The patient switches to the eccentric fixation point (in red) fortargets too large to visualize in the small central area. The resulting vision of aprinted page is simulated at right (2).

C o n t i n e n t o f A t r o p h y1 2

This article originally appeared in the April


1 0 s u p p l e m e n t

dry AMD. She noted that about 40 per-cent of eyes with geographic atrophy,which presents as loss of retinal pig-ment epithelium and photoreceptors,have visual acuity worse than 20/200.1

What’s more, the prevalence of geo-graphic atrophy is far greater in the veryold than wet AMD. Geographic atrophyaffects 22 percent of those older than90, while CNV affects 7 percent.2 Andmost patients have bilateral disease.“Geographic atrophy is the neglectedthief of vision,” Dr. Sunness said.

Why is it neglected? Geographicatrophy is more gradual than CNV, Dr.Sunness explained.“Geographic atrophyis a more orderly process. It progresses in a more predictable way.” And as thedisease progresses, blind spots developaround the center, coalescing into ahorseshoe and then a ring of atrophy.“It’s as though there’s a continent ofatrophy sitting in a sea of retina,” saidDr. Sunness. Throughout much of theprogression, the foveal center is spared,so the patient often maintains goodvisual acuity. Finally, the center is lost.

Blind, no, but impaired, yes. Func-tional problems can occur at any pointalong the dry AMD continuum, and yetthe perception exists, even among someretina specialists, that people with dryAMD don’t lose vision, said Dr. Mogk.She attributes this assumption to a 1984report stating that 10 percent of wetAMD accounts for 90 percent of legalblindness.3 But legal blindness is a gov-ernment construct, established to definethe point at which to compensate peoplewho are unable to support themselves,she explained. “Legal blindness is not anindex of function,” Dr. Mogk said, add-ing that the functional deficit beginslong before 20/200. “You can have sig-nificant vision loss without a definableblind spot,” she said, adding that manypeople with dry AMD and drusen havelost contrast sensitivity, which dramati-cally affects function. “With respect toacuity, by 20/50 you’re having difficulty,and at 20/70 you’re definitely in trouble.”

Geographic atrophy can be similarlyconfounding. Before the loss of fovealvision, patients may exhibit good single-letter visual acuity when tested on thechart, yet have difficulty reading or rec-

ognizing faces. Drs. Mogk and Sunnessboth have patients who can read news-print but not headlines, because a largeparacentral scotoma surrounds thespared foveal center that isn’t largeenough to contain the whole word. Thepatient can’t read the 20/400 letter onthe chart but can read the 20/50. Forsuch patients, simple magnification isoften ineffective.

Treatment Is ElusiveThere is not yet an established medicaltreatment to offer dry AMD patients.(See “Investigational Therapies for DryAMD.”) But these patients can be offeredhope. “Don’t say nothing can be done,”said Dr. Mogk.“Don’t tell patients they’ll

be blind. Tell them they will always haveusable vision and that there’s help outthere to use it optimally. Offer hope and encouragement, but don’t tell thesepatients that they’re lucky.”

1 Sunness, J. S. Mol Vis 1999;5:25.

2 Hirvela, H. et al. Ophthalmology 1996;106:

1768–1779.

3 Ferris, F. L. et al. Arch Ophthalmol 1984;

102:1640–1642.

Dr. Mogk has no related financial interests.

Dr. Rosenfeld is an investigator in clinical

trials funded by the NEI, Potentia Pharma-

ceuticals and Othera. Dr. Sunness has been

a consultant for Sytera (now merged with

Sirion), Neurotech and Othera.

R e t i n a

Attempts to fight dry AMD are under way. Here are some current investigations:

AREDS2. This NEI trial builds upon results from the earlier Age Related Eye DiseaseStudy, which found that high-dose antioxidant vitamins and minerals reduced therisk of progression to advanced AMD by 25 percent, and reduced the risk of mod-erate vision loss by 19 percent. AREDS2 will refine the findings by adding luteinand zeaxanthin to the formulation.

Ciliary neurotrophic factor (CNTF). Neurotech has developed an encapsulated celltechnology in which cells are engineered to produce CNTF, a naturally occurringsubstance that in animal models protected against further degeneration.

Complement inhibitors. Support for a paradigm that links aberrant complement acti-vation with AMD was revealed in studies associating AMD with three genes, includ-ing factor H. Collectively, the three gene variations account for nearly 75 percentof all AMD cases in European and North American populations.1 The unansweredquestion is whether inhibiting complement so late in the disease process will alterdisease progression or vision loss.

Glatiramer acetate. This drug, marketed as Copaxone, is an immunomodulatoryagent approved to treat relapsing-remitting multiple sclerosis. It may also work inthe eye. An ongoing study will test whether Copaxone arrests the progression aswell as the conversion of dry to wet AMD.

Fenretinide. This agent halts accumulation of lipofuscin and toxic vitamin Ametabolites. A two-year, phase 2 dose-ranging trial by Sirion is under way.

POT-4. Potentia Pharmaceuticals announced a phase 1 clinical trial in March 2007to test this complement inhibitor. POT-4 is designed to shut down the complementactivation system that could lead to local inflammation, tissue damage and upreg-ulation of angiogenic factors such as vascular endothelial growth factor.

OT-551. This agent, developed by Othera, may protect RPE cells and photorecep-tors from oxidative damage and block angiogenesis stimulated by VEGF and othergrowth factors. Othera is now conducting a randomized, double-masked, dose-ranging phase 2 trial. The NEI is also testing OT-551 in a pilot study of three-times-a-day dosing to halt progression of geographic atrophy.

1 Gold, B. et al. Nat Gene 2006;38(4):458–462.

I n v e s t i g a t i o n a l T h e r a p i e s f o r D r y A M D

e y e n e t s e l e c t i o n s 1 1

Classically described as endemicto a geographic belt thatincludes the Ohio River Valleyand the Mississippi River Val-ley, Histoplasma capsulatum,

a dimorphic mold, can affect the eye inmultiple ways. Ocular histoplasmosissyndrome (OHS) refers to a spectrumof disease extending from granuloma-tous fundus lesions to the developmentof choroidal neovascularization (CNV)and resultant disciform scarring. CNVresulting from OHS can cause severevision loss in a relatively young demo-graphic—usually during the third orfourth decade of life.

The route of inoculation with H. cap-sulatum is typically respiratory, andpatients may develop characteristicchorioretinal scars during a self-limitedsystemic infection, which is verified afterthe fact by positive skin antigen testing.That said, the antigen-disease relation-ship is still not clearly defined, with somepatients showing worsening of theirocular disease after a positive antigentest result. It has been postulated thatthe fraction of patients with OHS whogo on to develop macular findings maybe genetically predisposed. Certainhuman leukocyte antigens, such as HLA-B7 and HLA-DRw2, are more commonin patients with peripapillary CNV orsubmacular hemorrhage.1

DiagnosisOHS is a clinical diagnosis (see table,

next page) with a classic triad ofpunched-out peripheral choroidalscars, peripapillary pigmented degener-ation, and macular CNV or disciformscarring. The differential diagnosisincludes multifocal choroiditis, sar-coidosis, cryptococcosis, tuberculosis,coccidioidomycosis, pathologic myopia,punctate inner choroidopathy and age-related macular degeneration. Theabsence of vitritis in OHS helps to dis-tinguish it from other mycotic etiolo-gies. Age, absence of drusen and historydifferentiate it from macular degenera-tion. Refraction, absence of peripapillaryscleral show and absence of lacquercracks distinguish it from pathologic

myopia. Peripapillary pigmentationand/or atrophy is often found in indi-viduals without any visual complaints.The chorioretinal scars seen in OHS areoval-shaped,“punched out” lesions oftenseen near the posterior pole. Occasion-ally a linear streak of pigmented lesionsalso is seen near the equator.1 Whileasymptomatic characteristic chorio-retinal scarring may be seen on routineexamination, presentation with sub-retinal hemorrhage, retinal pigmentepithelium detachment, subretinal fluidor disciform scarring may confirm amore debilitating form of ocular histo-plasmosis. The presence of active CNVcan be confirmed with a combination

by srinivas s. iyengar, md, and david s. dyer, mdedited by ingrid u. scott, md, mph, and sharon fekrat, md

Ophthalmic Pearls

Diagnosing and TreatingHistoplasmosis

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RETINA

BEFORE AND AFTER: (1) Fluorescein angiogram and (2) OCT of an eye with visualacuity of 20/400 with leakage and subretinal hemorrhage. (3) FA and (4) OCTof the same eye one month after a single injection of ranibizumab; visual acuityis 20/30 and leakage has resolved.

1 3

2 4

This article originally appeared in the March



of optical coherence tomography andfluorescein angiography that revealssigns of early leakage, as well as by eval-uation by a retina specialist.

TreatmentMost patients with chorioretinal find-ings of OHS are asymptomatic and donot require any treatment. In those whodevelop associated CNV, prognosis andtreatment options depend on the loca-tion of the membrane—peripapillary,extrafoveal, juxtafoveal or subfoveal.

Peripapillary. Peripapillary pigment-ed degeneration, one of the characteris-tic fundus findings in histoplasmosis,may be the site of new CNV. Photo-dynamic therapy, while having benefitfor subfoveal lesions, carries the risk ofoptic nerve damage when used to treatperipapillary CNV. Thermal laser maybe a useful option but is associated witha risk of optic nerve damage from heattransfer. Intravitreal corticosteroids havebeen shown to be effective with theselesions but are associated with risk ofcataract and secondary glaucoma. Theuse of anti-VEGF drugs may be success-ful in treating peripapillary lesions, butsuch usage is not FDA-approved.

Extrafoveal. The Macular Photoco-agulation Study (MPS) Group estab-lished a treatment algorithm usingargon laser photocoagulation for extra-foveal membranes (greater than 200 µm

from the foveal center) associated withOHS after it showed that untreated eyeshad three to six times the risk of severevision loss than treated eyes. The MPSalso reported a 26 percent recurrencerate over five years in the treated mem-branes.2 For extrafoveal lesions, intra-vitreal injections of anti-VEGF drugsare another accepted option, but theycarry the discomfort of repeat injectionsand the risk of endophthalmitis.

Juxtafoveal. For juxtafoveal lesions,where the lesion edge is less than 200 µmfrom the foveal center, the MPS showedthat those treated with krypton laserwere less likely to develop severe visionloss (≥6 lines) when compared withobservation alone (11 vs. 30 percent).3

Many retina specialists believe thatthermal laser can be used to completelytreat lesions without infringing on thefoveal avascular zone; for lesions closerto the foveal avascular zone, PDT orpharmacotherapy may be preferred.Photodynamic therapy with verteporfinfor juxtafoveal lesions avoids the risk ofan expanding scar or scotoma associatedwith thermal laser and has been shownto result in visual improvement in 30percent of eyes and stabilization in 52percent of eyes.4 Intravitreal injectionof corticosteroid or anti-VEGF medica-tions are additional options, with manypatients opting for bevacizumab.

Subfoveal. With its potential to causegreater vision loss, laser treatment isavoided for subfoveal lesions. Physicalexcision of these membranes did notshow a statistically significant improve-ment in visual outcome in the Submac-ular Surgery Trial.5 As such, more favor-able options for subfoveal lesions causedby OHS that have been used includephotodynamic therapy and intravitrealcorticosteroid injections. Intravitrealbevacizumab, pegaptanib and ranibiz-umab are newer options that are cur-rently being used.

It is important to recognize that thesedrugs, when applied to histoplasmosis,are often not covered under insuranceplans. While it is not yet clear whetherthe benefits of ranibizumab therapy forneovascular AMD as described in theclinical trials extend to other causes ofCNV, multiple investigators at the 2007

ARVO annual meeting reported bene-fits of ranibizumab or bevacizumabinjections for OHS.

Watch for endophthalmitis. It isreassuring that most cases of OHS occurin healthy asymptomatic individualswho require only continued monitoringand use of an Amsler grid for signs of CNV. However, it is important toremember that H. capsulatum can alsocause an endogenous endophthalmitis.This is more often noted to occur inimmunocompromised patients, partic-ularly those with HIV infection.6 Poste-rior segment findings include multiple,white, creamy foci and a retinochoroidi-tis. Diagnosis is made based on thepresence of active pulmonary or dis-seminated histoplasmosis and positivecultures from sputum, the anteriorchamber or the vitreous cavity. Thetreatment options for these patientsinclude either systemic liposomalamphotericin B or itraconazole.6

ConclusionHistoplasmosis, while usually benign,can cause severe vision loss in patientsof any age and can demonstrate anaggressive course in the immunocom-promised population. The exact mecha-nism and/or role of H. capsulatum instimulating an immunologic responseand resultant chorioretinal scarringremains unclear at this time.

1 Hawkins, B. S. et al. “Ocular Histoplasmo-

sis,” in Retina, ed. S. J. Ryan et al. (Philadel-

phia: Mosby, 2006), 1749–1762.

2 Hawkins, B. S. et al. Arch Ophthalmol 1991;

109(8):1109 –1114.

3 Schachat, A. P. et al. Arch Ophthalmol 1994;

112(4):500–509.

4 Shah, G. K. et al. Retina 2005;25(1):26–32.

5 Hawkins, B. S. et al. Arch Ophthalmol

2004;122(11):1616–1628.

6 Moorthy, R. “Histoplasmosis,” in Ophthal-

mology, ed. M. Yanoff et al. (St. Louis: Mosby,

2004), xxii and 1652.

Dr. Iyengar is a staff ophthalmologist for

Orbis International, and Dr. Dyer is an

associate clinical professor of ophthalmolo-

gy there as well as a retina specialist at

Retina Associates in Kansas City, Kan.

Neither has related financial interests.

O p h t h a l m i c P e a r l s

Resident of histoplasmosis belt of theUnited States

Caucasian; 20 to 50 years of age

Classic Triad:● Multiple choroidal spots (“histo”

spots)● Peripapillary changes● CNV or disciform scar

No vitreous inflammatory disease

HLA-B7 positivity (macular disease)

SOURCE: Nussenblatt, R. B. “Ocular Histo-plasmosis,” in Uveitis: Fundamentals andClinical Practice, ed. R. B. Nussenblatt andS. M. Whitcup (Philadelphia: Mosby, 2004),235–242.

Characteristics of OcularHistoplasmosis Syndrome

BY MIRIAM KARMEL, CONTRIBUTING WRITER

The intravitreal injection, once considered a subspecialty skill, isbecoming more common in the dailywork of comprehensive Eye M.D.s.

ames M. Coombs, MD, is a community oph-thalmologist in Twin Falls, Idaho, a city thatserves the needs of people in the state’s ruralsouthern region. He and his partner at the

Fitzhugh Vision Clinic offer everything from cataractand refractive surgery to glaucoma care and even minoroculoplastics.

They also administer intravitreal bevacizumab(Avastin) injections to patients with neovascular age-related macular degeneration.

Whether a general ophthalmologist should be inject-ing drugs into the back of the eye is a matter of opinion—and some controversy. Prior to the availability of

bevacizumab and ranibizumab (Lucentis), few peoplequestioned the primacy of retina specialists in adminis-tering intravitreal (IVT) injections. The complexity ofearlier treatments dictated that they be managed byretina experts, according to Thomas A. Oetting, MD.“But it’s beginning to get into a simpler treatment pro-tocol.” Dr. Oetting is an associate professor of ophthal-mology at the University of Iowa in Iowa City.

In fact, IVT injections are becoming common insome clinics.“Injections of bevacizumab, ranibizumaband triamcinolone are more common than all retinalaser treatments combined in our vitreoretinal clinics atthe University of Iowa,” said James C. Folk, MD. “Thatis a huge shift from three years ago.” Dr. Folk is a profes-sor of ophthalmology, also at the University of Iowa.

J

The Intravitreal Injection The Intravitreal Injection Community Eye M.D.s TackleCommunity Eye M.D.s Tackle


This article originally appeared in the March 2008 issue ofEyeNet Magazine.


A New Scope of Practice DebateThis mini-revolution in care has fomented a rather pricklydebate over scope of practice between specialists and general-ists. Some retina specialists adamantly oppose the practice,arguing that IVT injections should be performed only by afellowship-trained vitreoretinal surgeon. Others more will-ingly accept the practice, albeit with caveats. All of them raisethe specter of endophthalmitis, questioning whether the gen-eralist has the skills to cope with it and other injection-inducedcomplications.

But many ophthalmologists, like Dr. Coombs—and Dr.Oetting, who was his mentor at the University of Iowa—con-tend that the general ophthalmologist can readily acquire therequisite skills and training to diagnose, evaluate and follow apatient with wet AMD, and even manage the complications.In areas where subspecialists are scarce, it may even be neces-sary for the comprehensive ophthalmologist to assume thisresponsibility. In fact, as the population ages and the AMDincidence increases, some general ophthalmologists are won-dering whether the time-consuming evaluation and injectionprotocol will overwhelm the practices of vitreoretinal sur-geons, even in areas where no scarcity of subspecialists exists.

Great expectations of eye residents. As director of the resi-dency program at the University of Iowa, Dr. Oetting gave alot of thought to this question: What is the scope of practicethat is expected of a general ophthalmologist? “Is managingfolks with macular degeneration in today’s world somethingwe should encourage our residents to become proficient in?”He regards the treatment of AMD with IVT injections as “oneof those border areas between what is expected of a generalophthalmologist and what is expected of a retina specialist.”

Dr. Oetting noted that general ophthalmologists performfocal laser treatment and panretinal photocoagulation with-out any objections.“Nobody argues that our residents shouldn’tdo those procedures, even though focal laser, like intravitrealinjections, requires facility with OCT and angiography.” Hesaid it is ironic that while most academic centers are filledwith subspecialists, resident ophthalmologists are expected to graduate with a broad set of skills. “We’ve been trying tofigure out what do our residents need to know to be a goodgeneral ophthalmologist? Should IVT be in that bag of tricks?”

He has decided it should. “IVT injections are somethingthat some general ophthalmologists will need to be doing.”

Patients Who Don’t Live Near SpecialistsThere are no retina specialists in Twin Falls, Idaho, but thereare a large number of AMD patients in Dr. Coombs’ practice.Knowing that if he didn’t treat them, they’d have to drive twohours to Boise or three hours to Salt Lake City, he and hispartner started to give the injections.

As a resident, Dr. Coombs did a few IVT injections, butanti-VEGF therapy wasn’t yet mainstream when he graduatedin 2006. So he learned the technique by observing his partnerand by viewing a video. He estimates that last year he gaveabout 70 injections, all without adverse outcomes. “The moreinjections I’ve done, the more comfortable I feel doing them.”

Technique, yes, but use judgment, too. Administering theinjection isn’t the primary objection of retina specialists.“Injection, per se, is not the issue for me,” said Dr. Folk, whohas developed a resident training protocol for IVT injections.“The issue for me is deciding when you need to do an injectionand when you do not.”

Peter K. Kaiser, MD, agrees. “The intravitreal injection isabsolutely something a general ophthalmologist can do.” Dr.Kaiser is director of the OCT Reading Center at the Cole EyeInstitute of the Cleveland Clinic. The question, he said, is“knowing when to do it and when not to do it. That’s where it becomes harder. You really have to know retina pretty wellto know when to deliver this or not, especially when talkingabout off-label drugs, like Avastin or triamcinolone.”

Julia A. Haller, MD, ophthalmologist-in-chief at the WillsEye Hospital in Philadelphia and president of the AmericanSociety of Retina Specialists, also agrees that comprehensiveophthalmologists are qualified to do IVT injections.“The issueis: Do they want to manage the kind of complicated vitreo-retinal pathology that these injections are designed to treat?”

While Dr. Coombs and his partner refer out retina surgicalcases, he is comfortable treating the majority of his AMDpatients without referral. “Most of the AMD cases I see arefairly straightforward,” he said. He stays current with the lit-erature, consults with friends in the retina community andcolleagues in Salt Lake City. He plans to buy an OCT for theoffice, but in the meantime follows patients with repeat fluo-rescein angiograms. He said he’s comfortable with fluoresceininterpretation, which was drilled into him during his residency.

Finally, Dr. Coombs refers difficult AMD cases, such as themonocular patient with an unusual presentation.“I felt I wanteda retina opinion before commencing,” he said, adding that thespecialist gave the injection in that case.

The Case for SpecialistsDr. Haller is sympathetic to the needs of rural communities.“I can see how in an underserved area, comprehensive oph-thalmologists might want to deal with it. And they should.”But, she added, the comprehensive ophthalmologist shouldconsider referral in areas well-served by retina specialists.“People up on the latest approaches are the specialists becausethat’s all they do. We’re completely focused on the latest wordon treating retinal diseases. Particularly in a time like the pres-ent, when there is a lot of fluidity concerning optimal man-agement strategies, most people would be best served by thosewho have thought the most about it.”

Dr. Kaiser agrees that general ophthalmologists can pro-vide an invaluable service in rural areas. His concern is withthe generalist who minimizes the complexity of these cases.Specifically, he said, there is an attitude among some generalophthalmologists that they can give patients the injection,and if it doesn’t work out, they can send the patient to a reti-na specialist. Some community eye care providers are eventreating patients with bevacizumab or ranibizumab without a fluorescein angiogram, Dr. Kaiser said. “It’s happening.” Heknows because he’s received some of those patients, including

IVT Injection Pearlshile the debate continues as to whether intravitrealinjections should be performed only by vitreoretinalsurgeons, Dr. Folk predicts that comprehensive

ophthalmologists will almost certainly see patients who willneed an IVT injection, or who already have had one or moreinjections. “It’s a very common procedure,” he said. Whatfollows is advice from Drs. Folk, Kaiser and Haller on how to give IVT injections, beginning with the cardinal rules forsterile technique:

Dr. Folk’s advice:● Use a lid specu-lum and anes-thetize the eyewith subconjuncti-val lidocaine.● Use povidoneiodine on the con-junctiva at theinjection site.● Don’t let theneedle (30-gauge) come intocontact with any-

thing—including the eyelashes—prior to injection.● Inject 3 mm posterior to the limbus in pseudophakiceyes, and 3.5 mm from the limbus in phakic eyes.● Direct the needle toward the optic nerve.● Insert the needle halfway and then inject.● Place a sterile Q-tip over the injection site before with-drawing the needle to prevent backflow of the drug or thevitreous.

Dr. Kaiser’s advice:● Set realistic expectations. Be sure the patient under-stands that the regimen involves multiple treatments.Explain that a repeat injection does not mean the treatmentis failing.● Be sure of the diagnosis before injecting.● Refer any patient who isn’t doing as well as you’d like.

Dr. Haller’s advice:● Be sure you are comfortable identifying, managing and/orreferring the potential complications of the injection,including retinal tear, retinal detachment, endophthalmitisand vitreous hemorrhage.● At the very least have somebody readily available forreferral.

Dr. Folk, who has developed a resident training protocol forintravitreal injections, demonstrates important aspects ofthe procedure, from the administration of lidocaine, upperright, to the treatment injection, lower right.J

AM

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. F

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K, M

D, B

RIC

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R, C

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Superotemporal, subconjunctival injection of lidocaine, 2 percent.

Speculum inserted after injection of anesthetic.

Calipers mark 3 mm from limbus in a pseudophakic eye.

A Q-tip is used to cover the injection site while needle is removed.

Sterile instruments needed for intravitrealinjection.

W



one who had been misdiagnosed with AMD and injectedunnecessarily.

First chance is best chance. Dr. Kaiser also had a patientwho’d been treated with bevacizumab at two-month intervals(contrary to the four-to-six week intervals many doctors arefollowing). The referring ophthalmologist in that case didn’thave any imaging devices and was treating on the basis of aclinical and vision exam. The delay in getting proper treat-ment could have cost the patient some vision, Dr. Kaiser said.“We only have so much time with these patients to do well.”

Because CNV, for example, can be misdiagnosed,“the deci-sion making to begin treatment to go down this anti-VEGFroad needs to be done by a retina specialist,” said Sharon Fekrat,MD, associate professor of ophthalmology at Duke Universityin Durham, N.C. The specialist also needs to decide at whatintervals to continue treatment, and when to stop it, she added.However, Dr. Fekrat can appreciate the value of collaborationbetween the specialist and general ophthalmologists “in selectsituations,” specifically where travel for care may be a hardshipon the patient.

The Case for ComanagementDr. Folk offered a comanagement scenario, especially forpatients who live a distance from the nearest specialist. Theretina expert could see the patient initially, make the diagno-sis and give the first injection. Then the comprehensive oph-thalmologist can give the next two injections. After the thirdinjection, the patient would return to the specialist for evalu-ation, Dr. Folk said. Returning to the specialist after the third

injection is important because that’s the “next real decisionpoint”—the time when treatment intervals may be adjustedaccording to need, he explained.

Dr. Folk suspects the number of comprehensive ophthal-mologists giving IVT injections will vary by region. In Iowa,where distances to a retina surgeon can be great, about 10percent of general ophthalmologists are giving IVT injections,though that number is likely to increase. “AMD is so commonand retina doctors are becoming almost overwhelmed withthe number of patients who need this,” he said. At the sametime, he knows there will be ophthalmologists who choosenot to give injections.

AMD numbers on the rise. Steve L. Gerber, MD, however,wants to treat AMD patients. “I’d like to learn because thenumber of patients needing injections and the number ofinjections needed are increasing along with the longevity ofour patient populations,” said Dr. Gerber, who is a compre-hensive ophthalmologist in private practice in South Bend,Ind. About 15 percent of his patients have AMD, and 10 per-cent of those have the neovascular form.

Dr. Gerber said that treating those patients is more feasiblebecause of OCT, which his office has. “OCT has allowed for amuch less invasive method of following these eyes over time.”And since he already gives anterior chamber injections andhas a glaucoma fellowship, he said, “It’s not much of a leap totreat these patients.”

In the meantime, Dr. Gerber refers all of his patients to the two “very excellent retina specialists,” in town. So far, hispatients are able to get appointments. But since the specialists

number of retina experts interviewed for this articlementioned the risk of serious adverse events fromIVT injection and even the potential for lawsuits.

Few medical complications. The potential hazards of IVTinjections generally, including endophthalmitis, retinaldetachment and intraocular hemorrhage, can be vision-threatening, but at least one study found that the risk ofserious adverse events is low.1 That study, by Rama D.Jager, MD, and colleagues, searched the literature viaPubMed from 1996 to 2004 to identify studies evaluatingthe safety of IVT injection. Data from 14,866 IVT injectionsin 4,382 eyes turned up 38 cases of endophthalmitis,including pseudo-endophthalmitis (0.3 percent prevalenceper injection). The search found that retinal detachmentwas uncommon after IVT injection, with an overall preva-lence of 0.9 percent per injection.

And few legal worries, as well. The risk of a lawsuit alsoappears to be low. At least for now, there is little evidencethat IVT injections have resulted in legal disputes. Asearch of the Ophthalmic Mutual Insurance Company’s(OMIC) active files revealed three “incident reports” relatedto bevacizumab injections out of a total of more than 800active claims, lawsuits and incident reports for all cate-

gories of adverse events. One of the three reports was dueto endophthalmitis, one was from a patient unhappy withresults and a third was for an injection into the wrong eye.

“Incidents,” said Paul Weber, JD, vice president ofOMIC’s risk management legal department, “are reportedon a precautionary basis by insureds. They don’t rise to the level of claims.” Mr. Weber found almost no activereports for other injectable retinal drugs. There was oneactive case report related to triamcinolone and none forranibizumab.

In fact, there have been so few reports involving IVTinjections that OMIC hasn’t considered which specialtyhad the incident. So for now, at least, OMIC doesn’trestrict coverage of its insured comprehensive ophthalmol-ogists who give IVT injections, Mr. Weber said. “Althoughwe have had general discussions at OMIC about the issue,there is no reason to be concerned about general ophthal-mologists doing it, unless and until it’s brought to ourattention by a number of claims. At this point, it hasn’tcome up as an item to take action upon, in either theclaims or underwriting departments.”

1 Retina 2004;24(5):676–698.

SO FAR: Low Incidence of Adverse Medical or Legal Events

A


cover a wide territory in northern Indiana and southern Mich-igan, he fears they could get overwhelmed, as the indicationsfor these injections grow. Dr. Gerber also wants simply to betterserve his patients.“From a patient service standpoint, it wouldbe good not to have to send them elsewhere,” he said.

A “Loved One” Rule of ThumbSo who should be treating AMD with IVT injections? For Dr.Folk, the answer comes down to the “loved one” rule. “If oneof my siblings needed an injection, I’d probably want a retinadoctor to do it,” he said.“But if she had to drive 50 miles everytime, and had a good comprehensive ophthalmologist to doit, I’d be okay with that, too.”

Dr. Coombs, whose patients have to drive much fartherthan 50 miles to see a retina specialist, said, “This is some-thing that can be treated safely and effectively by comprehen-sive ophthalmologists.” But, he added,“One needs to make acommitment to stay current on the evolving data emergingfrom these treatments, as retina specialists do.”

Special thanks to Dr. Folk and ophthalmic photographer Brice Critser

for images they shared for this story.

JAMES M. COOMBS, MD Private practitioner, Twin Falls, Idaho.

SHARON FEKRAT, MD Associate professor of ophthalmology, DukeUniversity, Durham, N.C.

JAMES C. FOLK, MD Professor of ophthalmology, University ofIowa, Iowa City.

STEVE L. GERBER, MD Private practitioner, South Bend, Ind.

JULIA A. HALLER, MD Ophthalmologist-in-chief, Wills Eye Hospi-tal, Philadelphia.

PETER K. KAISER, MD Director, OCT Reading Center, Cole EyeInstitute, Cleveland Clinic.

THOMAS A. OETTING, MD Associate professor of ophthalmology,University of Iowa, Iowa City.

PAUL WEBER, JD Vice president, risk management legal depart-ment, Ophthalmic Mutual Insurance Company, San Francisco.

None of the interviewees report related financial interests.

M E E T T H E E X P E R T S


Prompt and Aggressive Treatment Might Have Preserved This Mechanic’s Vision

Morning Rounds

by nikolas j. s. london, md, and emmett t. cunningham jr., md, phd, mphedited by thomas a. oetting, md

Initial Diagnosis Mr. Batista had no significant medicalhistory and had never seen an eye doctorbefore. He described his symptoms as“about a week of blurriness” that hadrecently been accompanied by “a littlepain” and “redness.” He acknowledgedmild photophobia but denied any othervisual or systemic symptoms.

On initial examination, Mr. Batistaseemed alert and oriented. His best-corrected visual acuity was 20/40 on the right and 20/30 on the left. His intra-ocular pressure and pupillary responseswere normal bilaterally. His slit-lampexamination revealed 3+ bilateral ante-rior inflammation with large, granulo-matous keratic precipitates. There wereno iris abnormalities. Dilated ophthal-moscopic examination revealed moder-ate vitritis, serous retinal detachments,and optic disc edema and hyperemia ineach eye. Initial workup included a CXR,RPR, MHA-TP, ANA, ESR, PPD, ACE

and lysozyme, all of which were unre-vealing.

Despite the presence of moderatevitritis, serous retinal detachment and

optic disc swelling, a nonspecific diag-nosis of granulomatous uveitis wasgiven, and Mr. Batista was started onhourly topical corticosteroids and acycloplegic/mydriatic agent. Over themonth following presentation, Mr.Batista’s symptoms progressed and hewas admitted to the hospital for evalua-tion of two weeks of blindness, dizzi-ness, leg weakness and nausea.

Diagnosis ReconsideredOnce in the hospital, Mr. Batista’s med-ical records were reviewed carefully andhe was noted to still have bilateral serous

Sergio Batista* was a hard-working mechanic with a wife and a newborn

daughter. One afternoon in the spring of 1995, he noticed some difficul-

ty reading the print on the label of an alternator he was about to install.

He tried blinking a few times, but this really didn’t help. Already several

cars behind schedule, this was the last thing he needed to worry about,

so he didn’t—he pushed on and finished his work. Unfortunately, things only got

worse over the next few days. His vision seemed to be getting blurrier, and his eyes

became red and painful. He knew it was time to see a doctor.

AT THE SLIT LAMP. This photo, taken 10 years after he first reported blurry vision,shows Koeppe nodules at the iris margin and Busacca nodules on the iris surface.

W h a t ’ s Y o u r D i a g n o s i s ?1

This article originally appeared in the April



retinal detachments. At this point, thediagnosis of Vogt-Koyanagi-Harada(VKH) syndrome was made. After ini-tial treatment with intravenous methyl-prednisolone, Mr. Batista’s vision andsystemic symptoms improved rapidly.He was discharged after several days,and he continued to improve on high-dose oral prednisone.

A Persistent Disease CourseOver the next 10 years, Mr. Batista expe-rienced frequent recurrences of ocularinflammation with waxing and waningsubretinal fluid. For eight years theserecurrences were treated with topicaland systemic corticosteroids. Althougheach episode resolved, his overall visualfunction gradually declined. In addition,he exhibited clear signs of corticosteroidtoxicity, including mood swings, weightgain and ocular hypertension.

In late 2003, he was started on sys-temic methotrexate, and he has been onvarious corticosteroid-sparing immuno-suppressive agents ever since. Theseagents have decreased the frequency ofhis recurrences but have not eliminatedthem altogether, nor have they preventedcomplications.

His corticosteroid-induced ocularhypertension required a trabeculectomyon his left eye in 2004, and he developedbilateral posterior subcapsular cataractsand underwent a left cataract extractionwith IOL implantation in 2005.

We Get a LookShortly after his cataract surgery, Mr.Batista presented to our clinic. At thisvisit he was in the midst of anotherrecurrence while on systemic cyclosporinA and topical corticosteroids.

What we saw. Examination revealedthat he had a BCVA of 20/40 on theright and 20/400 on the left.

His IOPs were 16 mmHg on the rightand 15 mmHg on the left.

Gonioscopy revealed open angles for360 degrees with scattered peripheralanterior synechiae and pigment bilater-ally. A shallow bleb was present superi-orly. There was moderate anteriorchamber cell with trace flare, scatterediris nodules (Fig. 1) and broad posteriorsynechiae bilaterally. A well-centeredposterior chamber IOL was present onthe left, whereas examination on theright showed moderate nuclear scleroticand posterior subcapsular cataract.

The ophthalmoscope revealed rarevitreous cell, a cup-to-disc ratio of 0.3,extensive alterations of retinal pigmentepithelium, widespread loss of choroidalmelanocytes producing a sunset-glowfundus, and scattered choroidal Dalen-Fuchs–like nodules bilaterally. Severalareas of subretinal fibrosis were noted(Figs. 2A and 2B), including a large areaof subfoveal fibrosis on the left.

Fluorescein angiography showed noevidence of active posterior segmentinflammation.

We make a management decision.Clinically, our patient had a 10-year his-tory of recurrent VKH syndrome com-plicated by glaucoma, cataract forma-tion and subretinal fibrosis when hepresented to us with active anterior seg-ment inflammation. As per prior reports,Mr. Batista denied any history of polio-sis, vitiligo or alopecia.

We restarted Mr. Batista on 40 mgprednisone with a slow taper, whilecontinuing his cyclosporin A, and heresponded well with resolution of hisanterior segment inflammation.

On his most recent visit, his BCVA was20/30 on the right and 20/200 on the left.

DiscussionIt is a multisystem disorder. VKH syn-drome is characterized by bilateralgranulomatous panuveitis associatedwith serous retinal detachments, opticdisc edema, neurologic abnormalitiesand skin pigmentary changes.

Systemic manifestations may includetinnitus, vitiligo, alopecia, headache andmeningismus. VKH syndrome isthought to be produced by a T cell–mediated autoimmune process directedagainst melanocyte antigens.

Its incidence varies. The syndrome has a higher prevalence in Asians, Lati-nos and American Indians, and isslightly more common in women thanin men. VKH syndrome may occur atany age but is particularly common in

M o r n i n g R o u n d s

FUNDUS FINDINGS. Photos of the right (2A) and left (2B) eyes show RPE alterations, loss of choroidal melanocytes and aresultant sunset-glow fundus, choroidal Dalen-Fuchs–like nodules, and subretinal fibrosis bilaterally.

2A 2B


the fourth to sixth decades of life.It has four phases. Classically, VKH

syndrome is described as having fourphases: prodromal, acute uveitic, conva-lescent and chronic recurrent. Classicfindings in the chronic recurrent phaseinclude RPE alterations, widespread lossof choroidal melanocytes producing asunset-glow fundus and choroidalDalen-Fuchs-like nodules which wereall present in our patient as well as cuta-neous vitiligo, poliosis and alopecia.

Complications may imperil vision.The chronic recurrent phase of VKHsyndrome is often accompanied byvision-threatening complications,including cataract, glaucoma, choroidalneovascular membranes, subretinalfibrosis, epiretinal membrane forma-tion and macular atrophy.1 These com-plications are common, with at leastone occurring in 42 percent of eyes.Cataract is the most common compli-cation, occurring in 30 to 42 percent ofeyes,2, 3 followed by glaucoma in 18 to45 percent of eyes,2, 3 choroidal neovas-cular membrane formation in 5 to 11percent of eyes,3 and subretinal fibrosisin 5 to 8 percent of eyes.

Certain findings on initial presenta-tion, such as poor visual acuity (lessthan 20/200), the presence of severeanterior chamber inflammation with or without posterior synechiae,2 andLatino ethnicity, may portend an in-creased risk of future complications,including more frequent recurrencesand poor long-term visual outcome.

The importance of prompt, aggres-sive therapy for VKH syndrome. Cur-rent guidelines urge prompt initiationof high-dose systemic corticosteroidtherapy (1 to 1.5 mg/kg/day) concur-rent with a corticosteroid-sparingimmunosuppressive agent, with thegoal of tapering patients off cortico-steroids within two to three months.4

Rapid and aggressive treatment isimportant to minimize disease dura-tion, lessen the risk of progression intoa chronic recurrent form of disease, andreduce the incidence of systemic andocular complications.2, 3, 5, 6

Treatment with systemic corticoste-roids reduces the risk of loss of visualacuity to 20/200 or worse in the better

seeing eye by 67 percent and reduces therisk of choroidal neovascularization orsubretinal fibrosis by 82 percent.1 Simi-larly, the use of immunosuppressivedrug therapy has been associated with a 67 percent risk reduction for visionloss to 20/50 or worse and a 92 percentrisk reduction for vision loss to 20/200or worse in better-seeing eyes.1

Mr. Batista’s Progress Our patient had a disease course thatwas particularly difficult to control. Thenumber and severity of the complica-tions in this case was probably due to anumber of factors, including the patient’sethnicity, the severity of the inflamma-tion at presentation, and the initial delayin use of systemic corticosteroids andcorticosteroid-sparing immunosup-pressive agents.

* Patient’s name is fictitious.

1 Bykhovskaya, I. et al. Am J Ophthalmol

2005;140:674–678.

2 Ohno, S. et al. Jpn J Ophthalmol 1988;

32:334–343.

3 Rubsamen, P. E. et al. Arch Ophthalmol

1991;109:6.

4 Damico, F. M. et al. Semin Ophthalmol

2005;20:183–190.

5 Moorthy, R. S. et al. Surv Ophthalmol 1995;

39:265–292.

6 Ohno, S. et al. Am J Ophthalmol 1977;83:

735–740.

Dr. London is a second-year resident at

California Pacific Medical Center in San

Francisco. Dr. Cunningham is currently

director of the uveitis service at CPMC and

an adjunct clinical professor of ophthalmol-

ogy at Stanford University.

This submission was supported in part by

The San Francisco Retina Foundation and

The Pacific Vision Foundation.

Go to www.eyenetmagazine.org for theonline version of this Morning Rounds,which has additional references forthe condition’s complications.

F u r t h e r R e a d i n g

The Bestof Retina AAO 2008

Health & Medicine

Transcript of The Bestof Retina AAO 2008