DiscussionThe indications for initiating

treatment and the modalities for

monitoring dis-ease activity arenot well estab-lished for patientswith BSR. Further,it is not clearwhether treatmentalters the long-term prognosisfor patients withthis chronic dis-ease. Physiciansin the OcularInflammatory

Disease Center of the Jules SteinInstitute are currently conducting astudy in collaboration with physi-

cians in France, following 75patients with BSR. Also, a study isbeing organized with physiciansfrom the Wilmer Eye Institute atJohns Hopkins University, as wellas from France and the Netherlands.This clinical research may helpophthalmologists better manageBSR patients in the future.

RECENT PUBLICATION Levinson RD, Gonzales CR. Birdshotretinochoroidopathy: Immunopathogenesis,evaluation and treatment. Ophthalmol Clinics NAm 2002;15:347–50

4 JSEI Clinical Update January 2004

CASE REPORT: BIRDSHOT RETINOCHOROIDOPATHY (continued from page 3)

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Figure 2: Visual fields (left eye shown on the left)

Save the Date:The annual JSEI Research and Alumni Day, Post ARVO Seminar, and Postgraduate Seminar and Jules Stein Lecture are now combined. The newly organized event, called the Jules Stein Eye Institute Clinical and Research Seminar will be held atthe Jules Stein Eye Institute on May 21–22, 2004. This year marks the first seminar, featuring the Thirty-fifthJules Stein Lecture, the Second Thomas H. Pettit Lecture, and the Second Bradley R. Straatsma Lecture.

Jules Stein LecturerRobert N. Weinreb, M.D., Shiley Eye Center at the University of California, San Diego

Thomas H. Pettit LecturerJames P. Dunn, Jr., M.D., Wilmer Eye Institute at The Johns Hopkins School of Medicine

Bradley R. Straatsma LecturerPaul S. Bernstein, M.D., Ph.D., Moran Eye Center at the University of Utah

2004

Thanks to technologic progress,managing retinopathy of prematu-

rity (ROP) can be a game of one-ups-manship, according to Christine R.Gonzales, M.D., Assistant Professor ofOphthalmology in the Retina Divisionat the Jules Stein Eye Institute. “Asmedical advances enable neonatolo-gists to keep smaller babies alive aswell as to treat systemic comorbiditiesof prematurity more adequately, often-times ROP may be the only illness withlong-term implications. Fortunately,newer surgical interventions and datahave refined techniques and providedpredictors for the success of varioustreatments for ROP,” Dr. Gonzales says.

Good CatchTo preclude visual disability from

this leading cause of blindness in chil-dren, screening is recommended forbabies weighing less than 1500 grams orwho are less than 28 weeks gestational

age (performed when they are between4 to 6 weeks of chronologic age or 31 to33 weeks postconception), criteria set bythe American Association of Pediatrics,the American Association of PediatricOphthalmology and Strabismus, and theAmerican Academy of Ophthalmology.At the Institute, children falling outsidethose parameters but with other factorsknown to increase the risk of ROP—such as long-term oxygen care or ane-mia—also are screened. Dr. Gonzalessays wide-field digital imaging anddetailed retina drawings are part of itsmultifaceted approach. “The digitalimaging allows us to follow the children,document and compare findingsbetween examinations, and evaluateresponse to treatment. It’s also useful foreducating families about the implicationsof ROP and getting them involved incare,” Dr. Gonzales notes.

Zone DefenseDigital imaging has furthermore

given retina specialists insights into thenatural history of ROP, including thedifferences between posterior (zone 1)disease and more anterior disease. AsDr. Gonzales explains, “The traditionalunderstanding of ROP is that there’s avisible ridge of tissue between the avascular and the vascular retina mark-ing the margin for laser treatment.However, in very posterior disease thatridge is much less visible, and neovas-cularization occurs not along an elevat-ed ridge, but is rather flat and extendsover a greater distance. We know nowthat untreated avascular regions withinthe retina provide a stimulus for vascu-lar endothelial growth factor (VEGF),which can drive neovascularization and

Photograph of the left fundusfrom a child born at 24 weeks

gestational age, weighing 970 grams demonstrating

Threshold ROP. Intraretinal hemorrhages, severe plus

disease, and neovascularizationare seen along the ridge.

Jules Stein Eye InstituteU C L A

(continued on page 2)

January 2004Volume 13, Number 1

Winning Against Retinopathy of Prematurity

ClinicalUpdate

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contribute to disease progression.” Because treatment must com-

pletely ablate the avascular retina,to avoid skip areas in the peripheryDr. Gonzales prefers using conflu-ent laser treatment, shown by somestudies to be superior to the non-confluent laser. Ongoing Instituteresearch to identify specific isotypesof VEGF involved in ROP patho-physiology could further refinetreatments for ROP.

Timing is EverythingWhatever the disease status,

Dr. Gonzales says speedy assess-ment and targeted treatment can-not be overemphasized to ensurethe best visual outcome. Besidesearly detection and referral, time-ly follow-up tailored to the sever-ity and rate of progression of dis-ease for each child are critical.Weekly follow-up is usually suffi-cient, but failure to respond totreatment as expected or rapidlyprogressing disease may signalmore frequent or aggressive fol-low-up. “Findings of moderate tosevere ‘plus disease’ (dilation andtortuosity of retinal vessels)implies likely progression tothreshold disease, so we mayeven perform laser treatment inthe prethreshold stage and notwait until threshold disease isreached,” Dr. Gonzales says.

Calling the PlayTreatment choices for ROP

have advanced along with infor-mation and technical develop-ments. Dr. Gonzales reports, “Wecan now recognize certain predic-tors of scleral buckling failure tohelp identify which patients maynot be ideal candidates for buck-ling. Additionally, high speed vit-reous cutters and wide angleviewing have improved our abili-ties to perform lens-sparing vitrec-tomy procedures.” Whereas initialtreatment for early retinal detach-ment was once scleral buckling,and failing that, vitrectomysurgery, children with stage 4Aretinal detachment have betteranatomic outcomes when treatedwith lens-sparing vitrectomy ini-tially rather than as last resort orsecondary to scleral buckle fail-ures. “If children are referred earlywith stage 4A detachments, we’reoften able to reattach the retina in90% or more of cases using lens-sparing vitrectomy. These childrendo not have the induced myopiaand the anisometropia that scleralbuckling can produce,” Dr.Gonzales says. “While cataract is apotential complication of vitrecto-my occurring in about 10-15% ofchildren, children treated withlens-sparing vitrectomy maintainthe natural shape of the eye,

which translates into better visualacuity outcomes.”

In the KeyTo track outcomes, the Institute

prospectively follows all childrenscreened in its Registry ofRetinopathy of Prematurity Patients,a database that includes digitalimages and clinical drawings.Additionally, for patients with diffi-cult management issues outsidehospital, digital imaging and state-of-the-art telecommunications sys-tems enable an exchange of databetween remote sites and either Dr.Gonzales or Dr. Steven Schwartz,Chief of the Retina Division, to con-firm or clarify ROP staging andmanagement possibilities. “Institutepilot studies comparing digital fun-dus images and indirect ophthal-moscopy findings demonstrated a95 to 97% positive predictive valuefor detecting pre-threshold orthreshold disease, plus disease, andretinal detachments,” she says.

The Institute is now participat-ing in the multicenter Photo-ROPtrial, hoping to validate the effec-tiveness of telemedicine for remoteassessment of ROP. Wielding thelatest data and technology to fightROP gives Dr. Gonzales and hercolleagues great satisfaction. Shesays, “Anything we can do to sup-port early diagnosis and augmenttreatment strategies will help pre-vent unnecessary blindness.”

REFERENCES:Shaikh S, Capone A., Jr, Schwartz SD, GonzalesC., Trese MT. Inadvertent Skip Areas inTreatment of Zone 1 Retinopathy of Prematurity;Photo Essay. Retina 2003; 23(1): 128-131.

Gonzales CR, Straatsma BR. Advances inRetinopathy of Prematurity. Screening,Diagnosis and Treatment. Brazilian Journal ofOphthalmology

2 JSEI Clinical Update January 2004

WINNING AGAINST RETINOPATHY OF PREMATURITY (continued from page 1)

Photograph of the left fundusof the same child, two weeksafter peripheral laser ablationfor Threshold ROP. Note complete regression of theridge, neovascularization, and plus disease.

TreatmentFluorescein angiography

showed mild staining of the largeretinal veins in the left eye, withoutmacular edema. Similarly, ocularcoherence tomography showed nomacular edema. A Humphrey visualfield was obtained (Fig. 2). Theright eye had foci of decreased sen-sitivity with a mean deviation of–2.61 dB and pattern standarddeviation of 3.93 dB. The left eyehad a dense inferior arcuate sco-toma, a mean deviation of –6.38dB, and pattern standard deviationof 7.43 dB. Color vision testingwith the D15 showed a color con-fusion score of 28 in the right eye

and 54 in the left eye, which aremoderately abnormal values.

The overall picture was consis-tent with birdshot retinochoroidopa-thy (BSR). The patient was found tohave the HLA-A29 genotype, whichis consistent with this diagnosis. TheHLA-A29 gene is present in 96% ormore of patients with BSR. Relativerisk is estimated to be as high as224, but it is not specific to the dis-ease, as about 7% of the Caucasianpopulation have this genotype.Therefore, BSR is still a clinical diag-nosis, even in patients who have theHLA-A29 gene. Other infectious,inflammatory and neoplastic (includ-ing lymphoma) causes of multifocal

choroiditis must also be considered,but the clinical picture in this patientwas very typical and an extensiveworkup was not needed. Since sar-coidosis is the disease that mostcommonly mimics BSR, a chest x-ray, angiotensin converting enzymelevel, and FTA-ABS were obtained,which were normal.

Decreased visual acuity sec-ondary to significant vitritis or cystoidmacular edema is a common indica-tion for therapy in BSR. But evenwith good Snellen visual acuity, mostpatients have great difficulty withvisual tasks and quality of life. Thispatient is a good example. She feltthat she could not function in termsof reading and driving. The evidenceof abnormalities on visual field andcolor vision tests was consistent withher having deficits at either the pho-toreceptor or ganglion cell level.These problems were not reflected inher Snellen visual acuity. Anothermodality that has been used to helpmake these decisions and monitorfunction is electrophysiologic testing,in particular electroretinography.

The patient was started on oralprednisone, 1 mg/kg/day, resultingin a significant decrease in her visu-al symptoms. The prednisone wastapered over a period of severalmonths, at which time cyclosporinewas started. While cyclosporine hasbeen one of the standard immuno-suppressive agents used in this dis-ease, it is not clear that it in anyway alters long-term prognosis.Antimetabolites, such as methotrex-ate or mycophenolate, have beenused as well. Since patients withBSR are often over 60, manynephrologists are hesitant to usecyclosporine on a long-term basis.

A 52-year-oldwoman presentedto her ophthalmolo-gist with a historyof visual distur-bances that shedescribed as floatersand “vibratingvision” in both eyes,over a period ofseveral months.Symptoms wereworse in the left eye.The ophthalmologistfound a posterior vitreous detachment in the left eye with no retinal tears. Treatment wasnot recommended. The symptoms persisted, and two months later theophthalmologist recognized mild vitritis and some hypopigmentedchoroidal lesions in both eyes. The patient was referred to the Jules SteinEye Institute for further evaluation.

On presentation, the patient was found to have best corrected visualacuity of 20/20 in the right eye and 20/25 in the left eye. There weretrace anterior chamber inflammatory cells and 1+ vitreous cells, as wellas haze without snowballs or snowbanking, in both eyes. There was novascular sheathing, and no cystoid macular edema. There were hypopig-mented choroidal lesions in the posterior segment of both eyes (Fig. 1).

Case Report: Birdshot Retinochoroidopathy

33January 2004 JSEI Clinical Update

(continued on page 4)

Figure 1: Hypopigmented birdshot lesions

The following case report was submitted by Ralph D. Levinson, MD, Assistant Professor of Ophthalmology, in theComprehensive Ophthalmology Division of the UCLA Jules Stein Eye Institute.