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The Best of RETINA
R E T I N A S U B S P E C I A LT Y D AY
AT L A N TA 2 0 0 8
5 Charles Bonnet Syndrome: When Visual Loss
Hallucinations may be a problem of the visual system and not
of cognitive function.
9 Dry AMD: Hope Is in the Pipeline
Wet AMD has garnered more attention, but that may soon
11 Diagnosing and Treating Histoplasmosis
A thorough look at managing this fungal infection.
Community Eye M.D.s Tackle the Intravitreal Injection
13 Many patients may come to rely on their primary ophthalmolo-
gist for their AMD therapy.
19 Prompt and Aggressive Treatment Might Have
Preserved This Mechanic’s Vision
This condition could challenge your medical skills.
Letter From the Editor
Dear Retina Subspecialty Day Attendee, apt method for preparing to get the most
Retinal medicine is in full flower these out of your sessions: Spend some time
days, with new insights into the origins of browsing through EyeNet Selections, the
macular degeneration, a deeper under- most relevant stories from one of the
standing of genetic retinal dystrophies most relevant years in your field.
and fantastic new imaging technologies
that capture associated pathologies in
“Vistas and Viewpoints” is the aptly Richard P. Mills, MD, MPH
named Retina Subspecialty Day at the Chief Medical Editor
Atlanta Meeting, and there is an equally EyeNet Magazine/EyeNet Selections
ON THE COVER: RPE alterations, loss of choroidal melanocytes and a resultant sunset-glow fundus, choroidal
Dalen-Fuchs–like nodules, and subretinal fibrosis bilaterally. Emmett T. Cunningham Jr., MD, PhD, MPH
4 s u p p l e m e n t
tools and techniques
Charles Bonnet Syndrome:
When Visual Loss Conjures Mischief
by miriam karmel, contributing writer
percent to 14 percent.1
alter J. Burghardt, SJ,
can’t see more than hand Gary C. Brown, MD, director of the Stung by Visions
motion with one eye or retina service at Wills Eye Institute in
count fingers at three feet Philadelphia and professor of ophthal-
with the other. Yet the 93- mology at Jefferson Medical College,
year-old Jesuit scholar and theologian and Melissa M. Brown, MD, adjunct
“sees” a country garden. Sometimes he assistant professor of ophthalmology at
even sees joggers, rows and rows of the University of Pennsylvania, wrote a
them, running through the greenery. paper not yet in print on CBS with Fr.
Fr. Burghardt, who lives in Philadel- Burghardt. They report that 59 percent
phia, has Charles Bonnet syndrome of 100 patients they looked at with neo-
(CBS), a disorder of visual hallucina- vascular AMD saw photopsias in the
tions that occurs in cognitively normal central visual field—whirly colored or
persons with severe bilateral visual loss white lights. Another 12 percent had
or deafferentation of the visual cortex. formed visual hallucinations, which in A patient of Dr. Golnik was tormented
In his case, the visual loss is due to neo- Fr. Burghardt’s case took the form of by bumblebee hallucinations.
vascular macular degeneration, though scenery and joggers. Others have reported
any visual impairment can trigger the seeing flowers, insects, buildings, faces in your leg, when you have no leg?” Yet
hallucinatory visions. The more severe and branching structures. some people do. When, for example, the
the impairment, the greater the chance nerve cells that once went to the foot
of having the visual aberrations, which Etiology Unknown and that continue to be represented in
can last seconds, minutes or hours. Charles Bonnet, the Swiss naturalist the brain become active, they can lead
“The hallucinations are often gen- and philosopher who first described to the perception that one’s foot is tin-
uinely formed and quite vivid,” said Eric the eponymous condition in 1760 after gling.“If you don’t have the normal
Eggenberger, DO, professor of neurolo- observing it in his 87-year-old mentally input from those nerve cells, then those
gy and ophthalmology at Michigan State alert grandfather, writes that “all of this nerve cells are free to go off on their
University. “The patients can tell you appears to have a seat in that part of the own direction,” Dr. Rovner explained.
minute details about the scenes they’re brain involved with sight.”2 Something similar happens with CBS
seeing. It’s almost like a running movie.” A failure to communicate. One cur- hallucinations, Dr. Rovner said. Some-
The etiology and the prevalence of rent theory holds that CBS is most often times, when the pathway between the
CBS are both ill-defined. related to direct damage to the visual eye and the occipital cortex is interrupt-
How common? In a review of the lit- system. A contrasting theory is that the ed, “those cells or their connections can
erature, Barry W. Rovner, MD, a geri- images represent release phenomena go haywire, do things on their own,
atric psychiatrist who conducts research due to deafferentation of the visual without regard to real stimuli.”
on depression and AMD, found the association areas of the cerebral cortex.1
prevalence of CBS patients attending It’s the same idea as phantom limb syn- “You’r e Not Going Crazy”
ophthalmology clinics ranges from 0.4 drome, explained Dr. Rovner, who is While seeing things that aren’t there
professor of psychiatry and neurology might sound distressing, most patients
This article originally appeared in the February at Jefferson Medical College in Philadel- report their visions in a nonemotional
2008 issue of EyeNet Magazine. phia. “Why would you feel something way. “They’re not distressed,” Dr. Eggen-
e y e n e t s e l e c t i o n s 5
berger said. “Patients describe it more
in the realm of a nuisance or a distrac- Banishing Bumblebees
tion, rather than something that’s dri-
ving them crazy.” verywhere I look, I’m seeing bumblebees,” a patient told Dr. Golnik. She’d
Still, the experts agree that it’s impor- lost vision in both eyes from giant cell arteritis and now “saw” bumblebees.
tant to reassure patients that they aren’t “What am I going to do?” she asked.
“crazy,” that they don’t have a psychi- While most patients are satisfied with an explanation that their hallucinations
atric disorder, but, rather, a recognized are the result of visual impairment and not a sign of dementia, others want more
condition with a name. And since there than reassurance. “Some patients are extremely tormented by the hallucinations,”
is no consistently effective treatment said Dr. Rovner. Those patients might benefit from medication, although there are
or generally agreed upon treatment for no drugs specifically approved for treating CBS. “We don’t know how to treat it
CBS, reassurance is often the best—and because there are no clinical trials,” said Dr. Rovner. “We’re left to an empirical
perhaps the only—thing a physician can approach to treatment.”
do for patients who are seeing things. Attempts to treat thus far. Since they’re dealing with hallucinations, doctors have
“The first thing I tell patients is, ‘This prescribed antipsychotic drugs that ordinarily treat schizophrenia, Dr. Rovner said.
does not mean you’re going nuts. This Antiseizure agents have also been tried, as well as donepezil, a cholinesterase
is a well-known phenomenon.’ It’s your inhibitor used for Alzheimer’s disease, and neuroleptic medications, such as
brain making up vision because you haloperidol or olanzapine.
can’t see anymore,’” said Karl C. Golnik, “It’s all anecdotal,” said Dr. Golnik, who has had mixed results treating CBS with
MD, professor of neuro-ophthalmology medication. “It’s not the case that you take medicine X and you will be better.”
and neurosurgery at the University of As a neuro-ophthalmologist, Dr. Eggenberger feels comfortable prescribing neu-
Cincinnati and the Cincinnati Eye Insti- roleptics, a potent class of medications with significant side effects. But he advised
tute. After this reassurance, said Dr. against a general ophthalmologist medicating for CBS. He said most of his patients
Golnik, some patients confess that they opt out of pharmacotherapy, preferring to live with the hallucinations than the side
were afraid to mention the hallucina- effects of the drugs.
tions, that they thought they were going Dr. Rovner was more emphatic about caution with treatment. “The psychiatrist
mad, even that they feared their children should be the prescribing physician for antipsychotic medications.”
would put them in a nursing home. In the case of the woman who saw bumblebees, Dr. Golnik prescribed trim-
Take the initiative. Because fear ipramine, after she called and told him, “This is driving me crazy. Stop it!”
can prevent patients from mentioning Trimipramine, a tricyclic antidepressant he had used with success on a different
the hallucinations, experts say doctors patient, helped decrease her symptoms, Dr. Golnik said. “She had a diminution in
should initiate the conversation. “I the number and what she called ‘intensity’ of the bees.”
would prefer for physicians, when they
have people with severe bilateral visual Is It CBS or Something Else? eyes, but the hallucinations may be a
loss, to educate them that this can Dr. Eggenberger said a diagnosis of CBS signal of something else going on in the
occur,” said Dr. Melissa Brown. requires ruling out widespread dementia brain. If a patient complains of systemic
Dr. Eggenberger agrees. While it’s or some other condition that more glob- symptoms such as numbness, tingling,
not necessary to discuss CBS with every ally affects cognition. weakness on one side of the body or a
patient, he advised raising the issue with To make a diagnosis of CBS, he new peripheral visual field defect, con-
any patient whose visual acuity is 20/100 advises looking for the following: sider stroke.
or 20/200 in both or the best seeing eye. ● A normal cognitive exam. ● If the patient is not aware that it’s a
“I couch it in benign terms,” he said, ● Absence of psychosis. hallucination and really believes his or
usually by saying, “It is possible that ● Normal attention level. her eyes, then that’s a red flag.
people develop visions when their vision ● Sufficient visual loss—20/100 or
is bad.” Then, rather than the accusato- 20/200 in both or the best-seeing eye. Tr eatment Options
ry inquiry, “Are you seeing things?” he Dr. Golnik said that if any of the fol- Some patients are extremely bothered
prefers, “Are your eyes playing tricks on lowing are observed, it’s probably not by the hallucinations. In that event, med-
you?” CBS: ication may be an option. (See “Banish-
Dr. Rovner uses similar phrasing, ● The patient had poor vision for ing Bumblebees.”)
such as, “Do you ever see anything that years, but only recently had hallucina- Referral to a low vision specialist
other people don’t see?” tions. CBS typically occurs around the is another option. Because the halluci-
Dr. Gary Brown reassures patients time of vision loss. nations tend to resolve when vision
that the hallucinations will go away with ● The patient has good vision in either improves, the patient might benefit
time. “Sometimes it can take weeks to eye. A diagnosis of CBS requires poor from instruction in improved lighting
months. But they do go away.” (See vision in both eyes. or the use of optical devices.
“Mind Over Mirage.”) ● Ophthalmologists think about the Dr. Melissa Brown aims for preserv-
6 s u p p l e m e n t
ing quality of life and mental outlook
in these patients. “Even if our patients
can’t see well, if we can just let them
know that what they’re seeing is an
expected phenomenon and not a
psychiatric event, then they accept
it and their quality of life is greatly
1 Rovner, B. W. Curr Opin Ophthalmol 2006;
2 Hedges, T. R. Surv Ophthalmol 2007;1:
Mind Over Mirage
Forgoing medication for his hallucina-
tions, Fr. Burghardt, who coauthored
a paper on CBS with Drs. Gary and
Melissa Brown, took matters into his
own hands, or rather, his own mind.
“Several months after my first experi-
ence of scenery, I was mulling over a
remark made, I believe, by my primary
ophthalmologist, Dr. Gary Brown:
In hallucinations the brain is giving
directions to the eyes,” writes Fr.
Then he had an inspiration. “I sat
straight up: This brain is my brain! . . .
I began talking to my brain. Directly,
as if person to person, even at times
as friend to friend. Softly, quietly, no
demands. Rather along these lines:
‘I notice your preference for red and
white. Would you favor me with a
small change? I like blue; it’s the
color dominating my living room.’ Not
much later blue began to appear. With
only rare reminders on my part, blue
gradually displaced more and more of
Fr. Burghardt has not been able
to eliminate the hallucinations com-
pletely, but he is pleased that he can
gain some power over them. “The
adventure with color, its unexpected
results, gave me a certain measure of
confidence. My brain is aware (at least
sometimes) of what I am thinking,
Fr. Burghardt passed away shortly after this
story appeared. We are grateful for his will-
ingness to share his experience with the
e y e n e t s e l e c t i o n s 7
tools and techniques
Hope Is in the Pipeline
by miriam karmel, contributing writer
he anti-VEGF agents beva-
cizumab (Avastin) and ranibiz-
Continent of Atrophy
umab (Lucentis) have trans- 1 2
formed the treatment of
neovascular macular degen-
eration. Finally, there is a treatment that
stops the leakage, dries the retina and in
many cases restores normal anatomy.
Still, some patients lose vision. Philip
J. Rosenfeld, MD, PhD, the doctor who
pioneered the use of the Avastin in the
eye, wanted to know why. After analyzing
data from the MARINA and ANCHOR
trials, he found there was no difference Macular perimetry with a scanning laser ophthalmoscope shows a dense ring sco-
in terms of CNV leakage between those toma (DS) surrounding central fixation (in red) which is interrupted by a second
who lost and those who gained three tiny scotoma (1). The patient switches to the eccentric fixation point (in red) for
lines of vision. targets too large to visualize in the small central area. The resulting vision of a
“We expected patients who lost printed page is simulated at right (2).
vision to have a greater amount of leak-
age from their CNV over time, but that “We don’t expect these drugs to become loss is associated with drusen or geo-
just wasn’t the case,” said Dr. Rosenfeld, ineffective over time because of muta- graphic atrophy, can have just as many
who is professor of ophthalmology at tions within the macula.” problems as patients with CNV, she
Bascom Palmer Eye Institute. “It said. Dr. Mogk is director of the Visual
appeared as though we successfully Dr y Needs Work Rehabilitation and Research Center of
converted the wet AMD back to dry Now the attention turns to dry AMD, the Henry Ford Health System in Detroit.
AMD. My hypothesis is that patients lose which ranges from patients with good In an analysis of 467 patient charts from
vision because their underlying dry mac- vision and drusen to patients with geo- 1999 to 2003—before the anti-VEGF
ular degeneration continues to progress.” graphic atrophy and visual acuities as treatments were in use—Dr. Mogk
Dr. Rosenfeld noted that interest poor as 20/200. Dr. Rosenfeld explained found that patients with dry AMD suf-
remains high in developing new treat- that dry AMD, just like any neurodegen- fered as much as those with CNV in most
ments for wet AMD, with a focus on erative disease, represents a challenging measures, including reading, depression,
combining therapeutic agents, similar to situation. In that regard, “Neovascular contrast sensitivity loss and the need for
the paradigm for cancer chemotherapy. AMD was the low-hanging fruit. Now rehabilitation training. “They’re trying
Unlike cancer, in which cells are geneti- we’ve got a very difficult problem in to figure out why they’re lucky,” she said.
LY L A S G . M O G K , M D
cally unstable and are always trying to attacking the dry AMD,” he said. The neglected thief of vision. Janet
find new ways to proliferate, AMD is a People with dry AMD will welcome S. Sunness, MD, medical director of the
genetically stable disease, he explained. this shift in attention. “Over and over Rehabilitation Services for Low Vision
they’re told, ‘You’re lucky you have dry and Blindness at the Greater Baltimore
This article originally appeared in the April AMD,’” said Lylas G. Mogk, MD. Yet Medical Center, agreed that there’s
2008 issue of EyeNet Magazine. patients with dry AMD, whose vision nothing lucky about having advanced
e y e n e t s e l e c t i o n s 9
dry AMD. She noted that about 40 per-
cent of eyes with geographic atrophy, Investigational Therapies for Dry AMD
which presents as loss of retinal pig-
ment epithelium and photoreceptors, Attempts to fight dry AMD are under way. Here are some current investigations:
have visual acuity worse than 20/200.1 AREDS2. This NEI trial builds upon results from the earlier Age Related Eye Disease
What’s more, the prevalence of geo- Study, which found that high-dose antioxidant vitamins and minerals reduced the
graphic atrophy is far greater in the very risk of progression to advanced AMD by 25 percent, and reduced the risk of mod-
old than wet AMD. Geographic atrophy erate vision loss by 19 percent. AREDS2 will refine the findings by adding lutein
affects 22 percent of those older than and zeaxanthin to the formulation.
90, while CNV affects 7 percent.2 And Ciliary neurotrophic factor (CNTF). Neurotech has developed an encapsulated cell
most patients have bilateral disease. technology in which cells are engineered to produce CNTF, a naturally occurring
“Geographic atrophy is the neglected substance that in animal models protected against further degeneration.
thief of vision,” Dr. Sunness said.
Complement inhibitors. Support for a paradigm that links aberrant complement acti-
Why is it neglected? Geographic
vation with AMD was revealed in studies associating AMD with three genes, includ-
atrophy is more gradual than CNV, Dr.
ing factor H. Collectively, the three gene variations account for nearly 75 percent
Sunness explained. “Geographic atrophy
of all AMD cases in European and North American populations.1 The unanswered
is a more orderly process. It progresses
question is whether inhibiting complement so late in the disease process will alter
in a more predictable way.” And as the
disease progression or vision loss.
disease progresses, blind spots develop
around the center, coalescing into a Glatiramer acetate. This drug, marketed as Copaxone, is an immunomodulatory
horseshoe and then a ring of atrophy. agent approved to treat relapsing-remitting multiple sclerosis. It may also work in
“It’s as though there’s a continent of the eye. An ongoing study will test whether Copaxone arrests the progression as
atrophy sitting in a sea of retina,” said well as the conversion of dry to wet AMD.
Dr. Sunness. Throughout much of the Fenretinide. This agent halts accumulation of lipofuscin and toxic vitamin A
progression, the foveal center is spared, metabolites. A two-year, phase 2 dose-ranging trial by Sirion is under way.
so the patient often maintains good POT-4. Potentia Pharmaceuticals announced a phase 1 clinical trial in March 2007
visual acuity. Finally, the center is lost. to test this complement inhibitor. POT-4 is designed to shut down the complement
Blind, no, but impaired, yes. Func- activation system that could lead to local inflammation, tissue damage and upreg-
tional problems can occur at any point ulation of angiogenic factors such as vascular endothelial growth factor.
along the dry AMD continuum, and yet
OT-551. This agent, developed by Othera, may protect RPE cells and photorecep-
the perception exists, even among some
tors from oxidative damage and block angiogenesis stimulated by VEGF and other
retina specialists, that people with dry
growth factors. Othera is now conducting a randomized, double-masked, dose-
AMD don’t lose vision, said Dr. Mogk.
ranging phase 2 trial. The NEI is also testing OT-551 in a pilot study of three-times-
She attributes this assumption to a 1984
a-day dosing to halt progression of geographic atrophy.
report stating that 10 percent of wet
AMD accounts for 90 percent of legal 1 Gold, B. et al. Nat Gene 2006;38(4):458–462.
blindness.3 But legal blindness is a gov-
ernment construct, established to define
the point at which to compensate people ognizing faces. Drs. Mogk and Sunness be blind. Tell them they will always have
who are unable to support themselves, both have patients who can read news- usable vision and that there’s help out
she explained. “Legal blindness is not an print but not headlines, because a large there to use it optimally. Offer hope
index of function,” Dr. Mogk said, add- paracentral scotoma surrounds the and encouragement, but don’t tell these
ing that the functional deficit begins spared foveal center that isn’t large patients that they’re lucky.”
long before 20/200. “You can have sig- enough to contain the whole word. The
nificant vision loss without a definable patient can’t read the 20/400 letter on 1 Sunness, J. S. Mol Vis 1999;5:25.
blind spot,” she said, adding that many the chart but can read the 20/50. For 2 Hirvela, H. et al. Ophthalmology 1996;106:
people with dry AMD and drusen have such patients, simple magnification is 1768–1779.
lost contrast sensitivity, which dramati- often ineffective. 3 Ferris, F. L. et al. Arch Ophthalmol 1984;
cally affects function. “With respect to 102:1640–1642.
acuity, by 20/50 you’re having difficulty, Tr eatment Is Elusive
and at 20/70 you’re definitely in trouble.” There is not yet an established medical Dr. Mogk has no related financial interests.
Geographic atrophy can be similarly treatment to offer dry AMD patients. Dr. Rosenfeld is an investigator in clinical
confounding. Before the loss of foveal (See “Investigational Therapies for Dry trials funded by the NEI, Potentia Pharma-
vision, patients may exhibit good single- AMD.”) But these patients can be offered ceuticals and Othera. Dr. Sunness has been
letter visual acuity when tested on the hope. “Don’t say nothing can be done,” a consultant for Sytera (now merged with
chart, yet have difficulty reading or rec- said Dr. Mogk.“Don’t tell patients they’ll Sirion), Neurotech and Othera.
10 s u p p l e m e n t
Diagnosing and Treating
by srinivas s. iyengar, md, and david s. dyer, md
edited by ingrid u. scott, md, mph, and sharon fekrat, md
lassically described as endemic 1 3
to a geographic belt that
includes the Ohio River Valley
and the Mississippi River Val-
ley, Histoplasma capsulatum,
a dimorphic mold, can affect the eye in
multiple ways. Ocular histoplasmosis
syndrome (OHS) refers to a spectrum
of disease extending from granuloma-
tous fundus lesions to the development
of choroidal neovascularization (CNV)
and resultant disciform scarring. CNV 2 4
resulting from OHS can cause severe
vision loss in a relatively young demo-
graphic—usually during the third or
fourth decade of life.
The route of inoculation with H. cap-
sulatum is typically respiratory, and
patients may develop characteristic BEFORE AND AFTER: (1) Fluorescein angiogram and (2) OCT of an eye with visual
chorioretinal scars during a self-limited acuity of 20/400 with leakage and subretinal hemorrhage. (3) FA and (4) OCT
systemic infection, which is verified after of the same eye one month after a single injection of ranibizumab; visual acuity
the fact by positive skin antigen testing. is 20/30 and leakage has resolved.
That said, the antigen-disease relation-
ship is still not clearly defined, with some next page) with a classic triad of myopia. Peripapillary pigmentation
patients showing worsening of their punched-out peripheral choroidal and/or atrophy is often found in indi-
ocular disease after a positive antigen scars, peripapillary pigmented degener- viduals without any visual complaints.
test result. It has been postulated that ation, and macular CNV or disciform The chorioretinal scars seen in OHS are
the fraction of patients with OHS who scarring. The differential diagnosis oval-shaped,“punched out” lesions often
go on to develop macular findings may includes multifocal choroiditis, sar- seen near the posterior pole. Occasion-
be genetically predisposed. Certain coidosis, cryptococcosis, tuberculosis, ally a linear streak of pigmented lesions
human leukocyte antigens, such as HLA- coccidioidomycosis, pathologic myopia, also is seen near the equator.1 While
B7 and HLA-DRw2, are more common punctate inner choroidopathy and age- asymptomatic characteristic chorio-
in patients with peripapillary CNV or related macular degeneration. The retinal scarring may be seen on routine
submacular hemorrhage.1 absence of vitritis in OHS helps to dis- examination, presentation with sub-
D AV I D S . D Y E R , M D
tinguish it from other mycotic etiolo- retinal hemorrhage, retinal pigment
Diagnosis gies. Age, absence of drusen and history epithelium detachment, subretinal fluid
OHS is a clinical diagnosis (see table, differentiate it from macular degenera- or disciform scarring may confirm a
tion. Refraction, absence of peripapillary more debilitating form of ocular histo-
This article originally appeared in the March scleral show and absence of lacquer plasmosis. The presence of active CNV
2008 issue of EyeNet Magazine. cracks distinguish it from pathologic can be confirmed with a combination
e y e n e t s e l e c t i o n s 11
from the foveal center) associated with ARVO annual meeting reported bene-
Characteristics of Ocular OHS after it showed that untreated eyes fits of ranibizumab or bevacizumab
Histoplasmosis Syndrome had three to six times the risk of severe injections for OHS.
Resident of histoplasmosis belt of the
vision loss than treated eyes. The MPS Watch for endophthalmitis. It is
also reported a 26 percent recurrence reassuring that most cases of OHS occur
rate over five years in the treated mem- in healthy asymptomatic individuals
Caucasian; 20 to 50 years of age
branes.2 For extrafoveal lesions, intra- who require only continued monitoring
Classic Triad: vitreal injections of anti-VEGF drugs and use of an Amsler grid for signs
● Multiple choroidal spots (“histo” are another accepted option, but they of CNV. However, it is important to
spots) carry the discomfort of repeat injections remember that H. capsulatum can also
● Peripapillary changes and the risk of endophthalmitis. cause an endogenous endophthalmitis.
● CNV or disciform scar Juxtafoveal. For juxtafoveal lesions, This is more often noted to occur in
No vitreous inflammatory disease where the lesion edge is less than 200 µm immunocompromised patients, partic-
HLA-B7 positivity (macular disease)
from the foveal center, the MPS showed ularly those with HIV infection.6 Poste-
that those treated with krypton laser rior segment findings include multiple,
SOURCE: Nussenblatt, R. B. “Ocular Histo- were less likely to develop severe vision white, creamy foci and a retinochoroidi-
plasmosis,” in Uveitis: Fundamentals and loss (≥ 6 lines) when compared with tis. Diagnosis is made based on the
Clinical Practice, ed. R. B. Nussenblatt and observation alone (11 vs. 30 percent).3 presence of active pulmonary or dis-
S. M. Whitcup (Philadelphia: Mosby, 2004), Many retina specialists believe that seminated histoplasmosis and positive
235–242. thermal laser can be used to completely cultures from sputum, the anterior
treat lesions without infringing on the chamber or the vitreous cavity. The
of optical coherence tomography and foveal avascular zone; for lesions closer treatment options for these patients
fluorescein angiography that reveals to the foveal avascular zone, PDT or include either systemic liposomal
signs of early leakage, as well as by eval- pharmacotherapy may be preferred. amphotericin B or itraconazole.6
uation by a retina specialist. Photodynamic therapy with verteporfin
for juxtafoveal lesions avoids the risk of Conclusion
Tr eatment an expanding scar or scotoma associated Histoplasmosis, while usually benign,
Most patients with chorioretinal find- with thermal laser and has been shown can cause severe vision loss in patients
ings of OHS are asymptomatic and do to result in visual improvement in 30 of any age and can demonstrate an
not require any treatment. In those who percent of eyes and stabilization in 52 aggressive course in the immunocom-
develop associated CNV, prognosis and percent of eyes.4 Intravitreal injection promised population. The exact mecha-
treatment options depend on the loca- of corticosteroid or anti-VEGF medica- nism and/or role of H. capsulatum in
tion of the membrane—peripapillary, tions are additional options, with many stimulating an immunologic response
extrafoveal, juxtafoveal or subfoveal. patients opting for bevacizumab. and resultant chorioretinal scarring
Peripapillary. Peripapillary pigment- Subfoveal. With its potential to cause remains unclear at this time.
ed degeneration, one of the characteris- greater vision loss, laser treatment is
tic fundus findings in histoplasmosis, avoided for subfoveal lesions. Physical 1 Hawkins, B. S. et al. “Ocular Histoplasmo-
may be the site of new CNV. Photo- excision of these membranes did not sis,” in Retina, ed. S. J. Ryan et al. (Philadel-
dynamic therapy, while having benefit show a statistically significant improve- phia: Mosby, 2006), 1749–1762.
for subfoveal lesions, carries the risk of ment in visual outcome in the Submac- 2 Hawkins, B. S. et al. Arch Ophthalmol 1991;
optic nerve damage when used to treat ular Surgery Trial.5 As such, more favor- 109(8):1109 –1114.
peripapillary CNV. Thermal laser may able options for subfoveal lesions caused 3 Schachat, A. P. et al. Arch Ophthalmol 1994;
be a useful option but is associated with by OHS that have been used include 112(4):500–509.
a risk of optic nerve damage from heat photodynamic therapy and intravitreal 4 Shah, G. K. et al. Retina 2005;25(1):26–32.
transfer. Intravitreal corticosteroids have corticosteroid injections. Intravitreal 5 Hawkins, B. S. et al. Arch Ophthalmol
been shown to be effective with these bevacizumab, pegaptanib and ranibiz- 2004;122(11):1616–1628.
lesions but are associated with risk of umab are newer options that are cur- 6 Moorthy, R. “Histoplasmosis,” in Ophthal-
cataract and secondary glaucoma. The rently being used. mology, ed. M. Yanoff et al. (St. Louis: Mosby,
use of anti-VEGF drugs may be success- It is important to recognize that these 2004), xxii and 1652.
ful in treating peripapillary lesions, but drugs, when applied to histoplasmosis,
such usage is not FDA-approved. are often not covered under insurance Dr. Iyengar is a staff ophthalmologist for
Extrafoveal. The Macular Photoco- plans. While it is not yet clear whether Orbis International, and Dr. Dyer is an
agulation Study (MPS) Group estab- the benefits of ranibizumab therapy for associate clinical professor of ophthalmolo-
lished a treatment algorithm using neovascular AMD as described in the gy there as well as a retina specialist at
argon laser photocoagulation for extra- clinical trials extend to other causes of Retina Associates in Kansas City, Kan.
foveal membranes (greater than 200 µm CNV, multiple investigators at the 2007 Neither has related financial interests.
12 s u p p l e m e n t
Community Eye M.D.s Tackle
The Intravitreal Injection
The intravitreal injection, once
considered a subspecialty skill, is
becoming more common in the daily
BY MIRIAM KARMEL, CONTRIBUTING WRITER work of comprehensive Eye M.D.s.
ames M. Coombs, MD, is a community oph- bevacizumab and ranibizumab (Lucentis), few people
J thalmologist in Twin Falls, Idaho, a city that
serves the needs of people in the state’s rural
southern region. He and his partner at the
Fitzhugh Vision Clinic offer everything from cataract
and refractive surgery to glaucoma care and even minor
questioned the primacy of retina specialists in adminis-
tering intravitreal (IVT) injections. The complexity of
earlier treatments dictated that they be managed by
retina experts, according to Thomas A. Oetting, MD.
“But it’s beginning to get into a simpler treatment pro-
oculoplastics. tocol.” Dr. Oetting is an associate professor of ophthal-
They also administer intravitreal bevacizumab mology at the University of Iowa in Iowa City.
(Avastin) injections to patients with neovascular age- In fact, IVT injections are becoming common in
related macular degeneration. some clinics. “Injections of bevacizumab, ranibizumab
Whether a general ophthalmologist should be inject- and triamcinolone are more common than all retina
ing drugs into the back of the eye is a matter of opinion laser treatments combined in our vitreoretinal clinics at
—and some controversy. Prior to the availability of the University of Iowa,” said James C. Folk, MD. “That
is a huge shift from three years ago.” Dr. Folk is a profes-
This article originally appeared in the March 2008 issue of sor of ophthalmology, also at the University of Iowa.
e y e n e t s e l e c t i o n s 13
A New Scope of Practice Debate Technique, yes, but use judgment, too. Administering the
This mini-revolution in care has fomented a rather prickly injection isn’t the primary objection of retina specialists.
debate over scope of practice between specialists and general- “Injection, per se, is not the issue for me,” said Dr. Folk, who
ists. Some retina specialists adamantly oppose the practice, has developed a resident training protocol for IVT injections.
arguing that IVT injections should be performed only by a “The issue for me is deciding when you need to do an injection
fellowship-trained vitreoretinal surgeon. Others more will- and when you do not.”
ingly accept the practice, albeit with caveats. All of them raise Peter K. Kaiser, MD, agrees. “The intravitreal injection is
the specter of endophthalmitis, questioning whether the gen- absolutely something a general ophthalmologist can do.” Dr.
eralist has the skills to cope with it and other injection-induced Kaiser is director of the OCT Reading Center at the Cole Eye
complications. Institute of the Cleveland Clinic. The question, he said, is
But many ophthalmologists, like Dr. Coombs—and Dr. “knowing when to do it and when not to do it. That’s where
Oetting, who was his mentor at the University of Iowa—con- it becomes harder. You really have to know retina pretty well
tend that the general ophthalmologist can readily acquire the to know when to deliver this or not, especially when talking
requisite skills and training to diagnose, evaluate and follow a about off-label drugs, like Avastin or triamcinolone.”
patient with wet AMD, and even manage the complications. Julia A. Haller, MD, ophthalmologist-in-chief at the Wills
In areas where subspecialists are scarce, it may even be neces- Eye Hospital in Philadelphia and president of the American
sary for the comprehensive ophthalmologist to assume this Society of Retina Specialists, also agrees that comprehensive
responsibility. In fact, as the population ages and the AMD ophthalmologists are qualified to do IVT injections.“The issue
incidence increases, some general ophthalmologists are won- is: Do they want to manage the kind of complicated vitreo-
dering whether the time-consuming evaluation and injection retinal pathology that these injections are designed to treat?”
protocol will overwhelm the practices of vitreoretinal sur- While Dr. Coombs and his partner refer out retina surgical
geons, even in areas where no scarcity of subspecialists exists. cases, he is comfortable treating the majority of his AMD
Great expectations of eye residents. As director of the resi- patients without referral. “Most of the AMD cases I see are
dency program at the University of Iowa, Dr. Oetting gave a fairly straightforward,” he said. He stays current with the lit-
lot of thought to this question: What is the scope of practice erature, consults with friends in the retina community and
that is expected of a general ophthalmologist? “Is managing colleagues in Salt Lake City. He plans to buy an OCT for the
folks with macular degeneration in today’s world something office, but in the meantime follows patients with repeat fluo-
we should encourage our residents to become proficient in?” rescein angiograms. He said he’s comfortable with fluorescein
He regards the treatment of AMD with IVT injections as “one interpretation, which was drilled into him during his residency.
of those border areas between what is expected of a general Finally, Dr. Coombs refers difficult AMD cases, such as the
ophthalmologist and what is expected of a retina specialist.” monocular patient with an unusual presentation.“I felt I wanted
Dr. Oetting noted that general ophthalmologists perform a retina opinion before commencing,” he said, adding that the
focal laser treatment and panretinal photocoagulation with- specialist gave the injection in that case.
out any objections.“Nobody argues that our residents shouldn’t
do those procedures, even though focal laser, like intravitreal The Case for Specialists
injections, requires facility with OCT and angiography.” He Dr. Haller is sympathetic to the needs of rural communities.
said it is ironic that while most academic centers are filled “I can see how in an underserved area, comprehensive oph-
with subspecialists, resident ophthalmologists are expected thalmologists might want to deal with it. And they should.”
to graduate with a broad set of skills. “We’ve been trying to But, she added, the comprehensive ophthalmologist should
figure out what do our residents need to know to be a good consider referral in areas well-served by retina specialists.
general ophthalmologist? Should IVT be in that bag of tricks?” “People up on the latest approaches are the specialists because
He has decided it should. “IVT injections are something that’s all they do. We’re completely focused on the latest word
that some general ophthalmologists will need to be doing.” on treating retinal diseases. Particularly in a time like the pres-
ent, when there is a lot of fluidity concerning optimal man-
Patients Who Don’t Live Near Specialists agement strategies, most people would be best served by those
There are no retina specialists in Twin Falls, Idaho, but there who have thought the most about it.”
are a large number of AMD patients in Dr. Coombs’ practice. Dr. Kaiser agrees that general ophthalmologists can pro-
Knowing that if he didn’t treat them, they’d have to drive two vide an invaluable service in rural areas. His concern is with
hours to Boise or three hours to Salt Lake City, he and his the generalist who minimizes the complexity of these cases.
partner started to give the injections. Specifically, he said, there is an attitude among some general
As a resident, Dr. Coombs did a few IVT injections, but ophthalmologists that they can give patients the injection,
anti-VEGF therapy wasn’t yet mainstream when he graduated and if it doesn’t work out, they can send the patient to a reti-
in 2006. So he learned the technique by observing his partner na specialist. Some community eye care providers are even
and by viewing a video. He estimates that last year he gave treating patients with bevacizumab or ranibizumab without
about 70 injections, all without adverse outcomes. “The more a fluorescein angiogram, Dr. Kaiser said. “It’s happening.” He
injections I’ve done, the more comfortable I feel doing them.” knows because he’s received some of those patients, including
14 s u p p l e m e n t
IVT Injection Pearls
hile the debate continues as to whether intravitreal
injections should be performed only by vitreoretinal
surgeons, Dr. Folk predicts that comprehensive
ophthalmologists will almost certainly see patients who will
need an IVT injection, or who already have had one or more
injections. “It’s a very common procedure,” he said. What
follows is advice from Drs. Folk, Kaiser and Haller on how
to give IVT injections, beginning with the cardinal rules for
Superotemporal, subconjunctival injection of lidocaine, 2 percent.
Dr. Folk’s advice:
● Use a lid specu-
lum and anes-
thetize the eye
● Use povidone
iodine on the con-
junctiva at the
● Don’t let the
Sterile instruments needed for intravitreal needle (30-
injection. gauge) come into
contact with any- Speculum inserted after injection of anesthetic.
thing—including the eyelashes—prior to injection.
● Inject 3 mm posterior to the limbus in pseudophakic
eyes, 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 the
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 treatment
is failing. Calipers mark 3 mm from limbus in a pseudophakic eye.
● Be sure of the diagnosis before injecting.
JAMES C. FOLK, MD, BRICE CRITSER, CRA
● 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/or
referring the potential complications of the injection,
including retinal tear, retinal detachment, endophthalmitis
and vitreous hemorrhage.
● At the very least have somebody readily available for
Dr. Folk, who has developed a resident training protocol for
intravitreal injections, demonstrates important aspects of
the procedure, from the administration of lidocaine, upper
right, to the treatment injection, lower right. A Q-tip is used to cover the injection site while needle is removed.
e y e n e t s e l e c t i o n s 15
one who had been misdiagnosed with AMD and injected injection is important because that’s the “next real decision
unnecessarily. point”—the time when treatment intervals may be adjusted
First chance is best chance. Dr. Kaiser also had a patient according to need, he explained.
who’d been treated with bevacizumab at two-month intervals Dr. Folk suspects the number of comprehensive ophthal-
(contrary to the four-to-six week intervals many doctors are mologists giving IVT injections will vary by region. In Iowa,
following). The referring ophthalmologist in that case didn’t where distances to a retina surgeon can be great, about 10
have any imaging devices and was treating on the basis of a percent of general ophthalmologists are giving IVT injections,
clinical and vision exam. The delay in getting proper treat- though that number is likely to increase. “AMD is so common
ment could have cost the patient some vision, Dr. Kaiser said. and retina doctors are becoming almost overwhelmed with
“We only have so much time with these patients to do well.” the number of patients who need this,” he said. At the same
Because CNV, for example, can be misdiagnosed, “the deci- time, he knows there will be ophthalmologists who choose
sion making to begin treatment to go down this anti-VEGF not to give injections.
road needs to be done by a retina specialist,” said Sharon Fekrat, AMD numbers on the rise. Steve L. Gerber, MD, however,
MD, associate professor of ophthalmology at Duke University wants to treat AMD patients. “I’d like to learn because the
in Durham, N.C. The specialist also needs to decide at what number of patients needing injections and the number of
intervals to continue treatment, and when to stop it, she added. injections needed are increasing along with the longevity of
However, Dr. Fekrat can appreciate the value of collaboration our patient populations,” said Dr. Gerber, who is a compre-
between the specialist and general ophthalmologists “in select hensive ophthalmologist in private practice in South Bend,
situations,” specifically where travel for care may be a hardship Ind. About 15 percent of his patients have AMD, and 10 per-
on the patient. cent of those have the neovascular form.
Dr. Gerber said that treating those patients is more feasible
The Case for Comanagement because of OCT, which his office has. “OCT has allowed for a
Dr. Folk offered a comanagement scenario, especially for much less invasive method of following these eyes over time.”
patients who live a distance from the nearest specialist. The And since he already gives anterior chamber injections and
retina expert could see the patient initially, make the diagno- has a glaucoma fellowship, he said, “It’s not much of a leap to
sis and give the first injection. Then the comprehensive oph- treat these patients.”
thalmologist can give the next two injections. After the third In the meantime, Dr. Gerber refers all of his patients to
injection, the patient would return to the specialist for evalu- the two “very excellent retina specialists,” in town. So far, his
ation, Dr. Folk said. Returning to the specialist after the third patients are able to get appointments. But since the specialists
SO FAR: Low Incidence of Adverse Medical or Legal Events
number of retina experts interviewed for this article gories of adverse events. One of the three reports was due
mentioned the risk of serious adverse events from to endophthalmitis, one was from a patient unhappy with
IVT injection and even the potential for lawsuits. results and a third was for an injection into the wrong eye.
Few medical complications. The potential hazards of IVT “Incidents,” said Paul Weber, JD, vice president of
injections generally, including endophthalmitis, retinal OMIC’s risk management legal department, “are reported
detachment and intraocular hemorrhage, can be vision- on a precautionary basis by insureds. They don’t rise to
threatening, but at least one study found that the risk of the level of claims.” Mr. Weber found almost no active
serious adverse events is low.1 That study, by Rama D. reports for other injectable retinal drugs. There was one
Jager, MD, and colleagues, searched the literature via active case report related to triamcinolone and none for
PubMed from 1996 to 2004 to identify studies evaluating ranibizumab.
the safety of IVT injection. Data from 14,866 IVT injections In fact, there have been so few reports involving IVT
in 4,382 eyes turned up 38 cases of endophthalmitis, injections that OMIC hasn’t considered which specialty
including pseudo-endophthalmitis (0.3 percent prevalence had the incident. So for now, at least, OMIC doesn’t
per injection). The search found that retinal detachment restrict coverage of its insured comprehensive ophthalmol-
was uncommon after IVT injection, with an overall preva- ogists who give IVT injections, Mr. Weber said. “Although
lence of 0.9 percent per injection. we have had general discussions at OMIC about the issue,
And few legal worries, as well. The risk of a lawsuit also there is no reason to be concerned about general ophthal-
appears to be low. At least for now, there is little evidence mologists doing it, unless and until it’s brought to our
that IVT injections have resulted in legal disputes. A attention by a number of claims. At this point, it hasn’t
search of the Ophthalmic Mutual Insurance Company’s come up as an item to take action upon, in either the
(OMIC) active files revealed three “incident reports” related claims or underwriting departments.”
to bevacizumab injections out of a total of more than 800
active claims, lawsuits and incident reports for all cate- 1 Retina 2004;24(5):676–698.
16 s u p p l e m e n t
cover a wide territory in northern Indiana and southern Mich-
igan, he fears they could get overwhelmed, as the indications
for these injections grow. Dr. Gerber also wants simply to better
serve his patients. “From a patient service standpoint, it would
be good not to have to send them elsewhere,” he said.
A “Loved One” Rule of Thumb
So who should be treating AMD with IVT injections? For Dr.
Folk, the answer comes down to the “loved one” rule. “If one
of my siblings needed an injection, I’d probably want a retina
doctor to do it,” he said. “But if she had to drive 50 miles every
time, and had a good comprehensive ophthalmologist to do
it, I’d be okay with that, too.”
Dr. Coombs, whose patients have to drive much farther
than 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 a
commitment to stay current on the evolving data emerging
from these treatments, as retina specialists do.”
Special thanks to Dr. Folk and ophthalmic photographer Brice Critser
for images they shared for this story.
MEET THE EXPERTS
JAMES M. COOMBS, MD Private practitioner, Twin Falls, Idaho.
SHARON FEKRAT, MD Associate professor of ophthalmology, Duke
University, Durham, N.C.
JAMES C. FOLK, MD Professor of ophthalmology, University of
Iowa, Iowa City.
STEVE L. GERBER, MD Private practitioner, South Bend, Ind.
JULIA A. HALLER, MD Ophthalmologist-in-chief, Wills Eye Hospi-
PETER K. KAISER, MD Director, OCT Reading Center, Cole Eye
Institute, 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.
e y e n e t s e l e c t i o n s 17
Prompt and Aggressive Treatment
Might Have Preserved This Mechanic’s Vision
by nikolas j. s. london, md, and emmett t. cunningham jr., md, phd, mph
edited by thomas a. oetting, md
optic disc swelling, a nonspecific diag-
ergio Batista* was a hard-working mechanic with a wife and a newborn
nosis of granulomatous uveitis was
daughter. One afternoon in the spring of 1995, he noticed some difficul-
given, and Mr. Batista was started on
ty reading the print on the label of an alternator he was about to install. hourly topical corticosteroids and a
He tried blinking a few times, but this really didn’t help. Already several cycloplegic/mydriatic agent. Over the
cars behind schedule, this was the last thing he needed to worry about, month following presentation, Mr.
Batista’s symptoms progressed and he
so he didn’t—he pushed on and finished his work. Unfortunately, things only got
was admitted to the hospital for evalua-
worse over the next few days. His vision seemed to be getting blurrier, and his eyes tion of two weeks of blindness, dizzi-
became red and painful. He knew it was time to see a doctor. ness, leg weakness and nausea.
Initial Diagnosis and lysozyme, all of which were unre- Diagnosis Reconsider ed
Mr. Batista had no significant medical vealing. Once in the hospital, Mr. Batista’s med-
history and had never seen an eye doctor Despite the presence of moderate ical records were reviewed carefully and
before. He described his symptoms as vitritis, serous retinal detachment and he was noted to still have bilateral serous
“about a week of blurriness” that had
recently been accompanied by “a little W h a t ’s Yo u r D i a g n o s i s ?
pain” and “redness.” He acknowledged
mild photophobia but denied any other 1
visual or systemic symptoms.
On initial examination, Mr. Batista
seemed 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 responses
were normal bilaterally. His slit-lamp
examination revealed 3+ bilateral ante-
rior inflammation with large, granulo-
matous keratic precipitates. There were
no iris abnormalities. Dilated ophthal-
moscopic examination revealed moder-
ate vitritis, serous retinal detachments,
and optic disc edema and hyperemia in
each eye. Initial workup included a CXR,
RPR, MHA-TP, ANA, ESR, PPD, ACE
AT THE SLIT LAMP. This photo, taken 10 years after he first reported blurry vision,
This article originally appeared in the April
shows Koeppe nodules at the iris margin and Busacca nodules on the iris surface.
2008 issue of EyeNet Magazine.
e y e n e t s e l e c t i o n s 19
FUNDUS FINDINGS. Photos of the right (2A) and left (2B) eyes show RPE alterations, loss of choroidal melanocytes and a
resultant sunset-glow fundus, choroidal Dalen-Fuchs–like nodules, and subretinal fibrosis bilaterally.
retinal detachments. At this point, the We Get a Look We make a management decision.
diagnosis of Vogt-Koyanagi-Harada Shortly after his cataract surgery, Mr. Clinically, our patient had a 10-year his-
(VKH) syndrome was made. After ini- Batista presented to our clinic. At this tory of recurrent VKH syndrome com-
tial treatment with intravenous methyl- visit he was in the midst of another plicated by glaucoma, cataract forma-
prednisolone, Mr. Batista’s vision and recurrence while on systemic cyclosporin tion and subretinal fibrosis when he
systemic symptoms improved rapidly. A and topical corticosteroids. presented to us with active anterior seg-
He was discharged after several days, What we saw. Examination revealed ment inflammation. As per prior reports,
and he continued to improve on high- that he had a BCVA of 20/40 on the Mr. Batista denied any history of polio-
dose oral prednisone. right and 20/400 on the left. sis, vitiligo or alopecia.
His IOPs were 16 mmHg on the right We restarted Mr. Batista on 40 mg
A Per sistent Disease Cour se and 15 mmHg on the left. prednisone with a slow taper, while
Over the next 10 years, Mr. Batista expe- Gonioscopy revealed open angles for continuing his cyclosporin A, and he
rienced frequent recurrences of ocular 360 degrees with scattered peripheral responded well with resolution of his
inflammation with waxing and waning anterior synechiae and pigment bilater- anterior segment inflammation.
subretinal fluid. For eight years these ally. A shallow bleb was present superi- On his most recent visit, his BCVA was
recurrences were treated with topical orly. There was moderate anterior 20/30 on the right and 20/200 on the left.
and systemic corticosteroids. Although chamber cell with trace flare, scattered
each episode resolved, his overall visual iris nodules (Fig. 1) and broad posterior Discussion
function gradually declined. In addition, synechiae bilaterally. A well-centered It is a multisystem disorder. VKH syn-
he exhibited clear signs of corticosteroid posterior chamber IOL was present on drome is characterized by bilateral
toxicity, including mood swings, weight the left, whereas examination on the granulomatous panuveitis associated
gain and ocular hypertension. right showed moderate nuclear sclerotic with serous retinal detachments, optic
In late 2003, he was started on sys- and posterior subcapsular cataract. disc edema, neurologic abnormalities
temic methotrexate, and he has been on The ophthalmoscope revealed rare and skin pigmentary changes.
various corticosteroid-sparing immuno- vitreous cell, a cup-to-disc ratio of 0.3, Systemic manifestations may include
suppressive agents ever since. These extensive alterations of retinal pigment tinnitus, vitiligo, alopecia, headache and
agents have decreased the frequency of epithelium, widespread loss of choroidal meningismus. VKH syndrome is
his recurrences but have not eliminated melanocytes producing a sunset-glow thought to be produced by a T cell–
them altogether, nor have they prevented fundus, and scattered choroidal Dalen- mediated autoimmune process directed
complications. Fuchs–like nodules bilaterally. Several against melanocyte antigens.
His corticosteroid-induced ocular areas of subretinal fibrosis were noted Its incidence varies. The syndrome
hypertension required a trabeculectomy (Figs. 2A and 2B), including a large area has a higher prevalence in Asians, Lati-
on his left eye in 2004, and he developed of subfoveal fibrosis on the left. nos and American Indians, and is
bilateral posterior subcapsular cataracts Fluorescein angiography showed no slightly more common in women than
and underwent a left cataract extraction evidence of active posterior segment in men. VKH syndrome may occur at
with IOL implantation in 2005. inflammation. any age but is particularly common in
20 s u p p l e m e n t
the fourth to sixth decades of life. seeing eye by 67 percent and reduces the
It has four phases. Classically, VKH risk of choroidal neovascularization or
syndrome is described as having four subretinal fibrosis by 82 percent.1 Simi-
phases: prodromal, acute uveitic, conva- larly, the use of immunosuppressive
lescent and chronic recurrent. Classic drug therapy has been associated with
findings in the chronic recurrent phase a 67 percent risk reduction for vision
include RPE alterations, widespread loss loss to 20/50 or worse and a 92 percent
of choroidal melanocytes producing a risk reduction for vision loss to 20/200
sunset-glow fundus and choroidal or worse in better-seeing eyes.1
Dalen-Fuchs-like nodules which were
all present in our patient as well as cuta- Mr. Batista’s Progr ess
neous vitiligo, poliosis and alopecia. Our patient had a disease course that
Complications may imperil vision. was particularly difficult to control. The
The chronic recurrent phase of VKH number and severity of the complica-
syndrome is often accompanied by tions in this case was probably due to a
vision-threatening complications, number of factors, including the patient’s
including cataract, glaucoma, choroidal ethnicity, the severity of the inflamma-
neovascular membranes, subretinal tion at presentation, and the initial delay
fibrosis, epiretinal membrane forma- in use of systemic corticosteroids and
tion and macular atrophy.1 These com- corticosteroid-sparing immunosup-
plications are common, with at least pressive agents.
one occurring in 42 percent of eyes.
Cataract is the most common compli- * Patient’s name is fictitious.
cation, occurring in 30 to 42 percent of
eyes,2, 3 followed by glaucoma in 18 to 1 Bykhovskaya, I. et al. Am J Ophthalmol
45 percent of eyes,2, 3 choroidal neovas- 2005;140:674–678.
cular membrane formation in 5 to 11 2 Ohno, S. et al. Jpn J Ophthalmol 1988;
percent of eyes,3 and subretinal fibrosis 32:334–343.
in 5 to 8 percent of eyes. 3 Rubsamen, P. E. et al. Arch Ophthalmol
Certain findings on initial presenta- 1991;109:6.
tion, such as poor visual acuity (less 4 Damico, F. M. et al. Semin Ophthalmol
than 20/200), the presence of severe 2005;20:183–190.
anterior chamber inflammation with 5 Moorthy, R. S. et al. Surv Ophthalmol 1995;
or without posterior synechiae,2 and 39:265–292.
Latino ethnicity, may portend an in- 6 Ohno, S. et al. Am J Ophthalmol 1977;83:
creased risk of future complications, 735–740.
including more frequent recurrences
and poor long-term visual outcome. Dr. London is a second-year resident at
The importance of prompt, aggres- California Pacific Medical Center in San
sive therapy for VKH syndrome. Cur- Francisco. Dr. Cunningham is currently
rent guidelines urge prompt initiation director of the uveitis service at CPMC and
of high-dose systemic corticosteroid an adjunct clinical professor of ophthalmol-
therapy (1 to 1.5 mg/kg/day) concur- ogy at Stanford University.
rent with a corticosteroid-sparing
immunosuppressive agent, with the This submission was supported in part by
goal of tapering patients off cortico- The San Francisco Retina Foundation and
steroids within two to three months.4 The Pacific Vision Foundation.
Rapid and aggressive treatment is
important to minimize disease dura-
tion, lessen the risk of progression into
a chronic recurrent form of disease, and
reduce the incidence of systemic and Go to www.eyenetmagazine.org for the
ocular complications.2, 3, 5, 6 online version of this Morning Rounds,
Treatment with systemic corticoste- which has additional references for
roids reduces the risk of loss of visual the condition’s complications.
acuity to 20/200 or worse in the better
e y e n e t s e l e c t i o n s 21