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Long-term Visual Outcomes of Intravitreal Bevacizumabin Inflammatory Ocular Neovascularization

AHMAD M. MANSOUR, J. FERNANDO AREVALO, FOCKE ZIEMSSEN, ABLA MEHIO-SIBAI,FRIEDERIKE MACKENSEN, ALFREDO ADAN, WAI-MAN CHAN, THOMAS NESS, ALAY S. BANKER,

DAVID DODWELL, THI HA CHAU TRAN, CHRISTINE FARDEAU, PHUC LEHOANG,PADMAMALINI MAHENDRADAS, MARIA BERROCAL, ZUHEIR TABBARAH, NICHOLAS HRISOMALOS,

FRANK HRISOMALOS, KHALIL AL-SALEM, AND RAINER GUTHOFF

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PURPOSE: To assess the long-term role of bevacizumabAvastin; Genentech Inc, South San Francisco, Califor-ia, USA) in inflammatory ocular neovascularization.DESIGN: Retrospective multicenter consecutive case

eries of inflammatory ocular neovascularization.METHODS: SETTINGS: Multicenter institutional and pri-

ate practices. STUDY POPULATION: Patients with inflam-atory ocular neovascularization in one or both eyes ofarying etiologies who failed standard therapy. INTERVEN-ION: Intravitreal injection of bevacizumab. MAIN OUT-OME MEASURES: Improvement of best-corrected visualcuity (BCVA) expressed as logarithm of minimal anglef resolution (logMAR), and decrease in central fovealhickness as measured by optical coherence tomographyt 6, 12, 18, and 24 months of follow-up.RESULTS: Mean logMAR BCVA (central foveal thick-

ess) following intravitreal bevacizumab was as follows:aseline, 0.65 (6/27 or 20/90) (338 �m; 99 eyes of 96atients); 6 months, 0.42 (6/16 or 20/53) (239 �m; 2.0njections; 81 eyes); 12 months, 0.39 (6/15 or 20/49)241 �m; 2.3 injections; 95 eyes); 18 months, 0.406/15 or 20/50) (261 �m; 3.0 injections; 46 eyes); and4 months, 0.34 (6/13 or 20/44) (265 �m; 3.6 injec-ions; 27 eyes). Paired comparisons revealed significant

ccepted for publication Mar 16, 2009.From the Departments of Ophthalmology (A.M.M., K.A.-S.), Epide-iology and Population Health (A.M.-S.), and Internal Medicine (Z.T.),merican University of Beirut, Beirut, Lebanon; Rafic Hariri Universityospital (A.M.M., Z.T.), Beirut, Lebanon; Clinica Oftalmologica Centroaracas (F.A.), University of Los Andes, Caracas, Venezuela; Depart-ent of Ophthalmology (F.Z.), University of Tuebingen, Tuebingen,ermany; Interdisciplinary Uveitis Center (F.M.), University of Heidel-

erg, Heidelberg, Germany; Department of Ophthalmology (A.A.),ospital Clinic de Barcelona, Universidad de Barcelona, Barcelona,pain; Department of Ophthalmology (W.-M.C.), Chinese University ofong Kong, Hong Kong Sanatorium & Hospital, Happy Valley, Hongong; University Eye Hospital (T.N.), Freiburg, Germany; Banker’setina Clinic and Laser Center (A.S.B.), Ahmedabad, Gujarat, India;pringfield Eye Clinic (D.D.), Springfield, Illinois; Department of Oph-halmology (T.H.C.T., C.F., P.L.), Groupe Hospitalier Pitié Salpêtrière,aris, France; Departments of Uveitis and Retina (P.M.), Narayanaethralaya, Bangalore, India; Department of Ophthalmology (M.B.),niversity of Puerto Rico, San Juan, Puerto Rico; Department ofphthalmology (N.H., F.H.), Indiana University, Indianapolis, Indiana;

nd Department of Ophthalmology (R.G.), University of Wuerzburg,uerzburg, Germany.Inquiries to Ahmad M. Mansour, Department of Ophthalmology,

american University of Beirut, PO 113-6044, Beirut, Lebanon; e-mail:

r.ahmad@cyberia.net.lb

© 2009 BY ELSEVIER INC. A10

isual improvement at 6 months of 2.4 lines (P � .000),t 12 months of 2.5 lines (P � .000), at 18 months of.5 lines (P � .001), and at 24 months of 2.2 lines (P �013). Paired comparisons revealed significant centraloveal flattening at 6 months of 78 �m (P � .000), at 12onths of 85 �m (P � .000), at 18 months of 90 �m

P � .003), and at 24 months of 77 �m (P � .022).hree eyes developed submacular fibrosis and 1 eye

ubmacular hemorrhage.CONCLUSION: Intravitreal bevacizumab led in the

ong-term to significant mean visual improvement of >2.2ines and significant foveal flattening in a wide variety ofnflammatory ocular diseases without major complications.Am J Ophthalmol 2009;148:310–316. © 2009 bylsevier Inc. All rights reserved.)

HOROIDAL NEOVASCULARIZATION (CNV) AND NEO-

vascularization of the disc or elsewhere (NVD/E) inthe retina can be an occasionally late sequela of

nflammatory chorioretinal diseases,1 and rarely an earlyanifestation.2 Our group has previously reported the

-month results of intravitreal bevacizumab (Avastin;enentech Inc, South San Francisco, California, USA) in

nflammatory ocular neovascularization in 84 eyes. Intra-itreal bevacizumab led to short-term significant visualmprovement and regression of inflammatory ocular neo-ascularization in a wide variety of inflammatory oculariseases.3

The long-term safety profile of bevacizumab, and visualrognosis in inflammatory ocular neovascularization, maye jeopardized by submacular fibrosis,4,5 cystoid maculardema (CME),6–8 or spread of chorioretinal atrophy. Thebjective of this report is to assess the long-term safety andfficacy of intravitreal bevacizumab in a retrospectiveollaborative case series study of inflammatory oculareovascularization.

METHODS

ONSECUTIVE CASES OF INFLAMMATORY OCULAR NEO-

ascularization resistant to corticosteroid with or without

ntimicrobial therapy and/or immunosuppression treated

LL RIGHTS RESERVED. 0002-9394/09/$36.00doi:10.1016/j.ajo.2009.03.023

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ith intravitreal bevacizumab and followed for more thanmonths were included in the present analysis. The casesere contributed by members of the American Society ofetina Specialists and the American Uveitis Society asetailed elsewhere.3 Intravitreal bevacizumab was injectedsing a 30-gauge needle in a sterile manner after topicalnesthesia and povidone instillation in the lower cul-de-ac. Bevacizumab aliquots were prepared in the hospitalharmacies of the corresponding institution.A standardized spreadsheet was used to collect the

linical data. Cases with prior CME, diabetes mellitus, orge-related macular degeneration were excluded. Most ofhe patients had initially been treated in a stepwise fashionith high-doses of oral corticosteroid, with or without

ntraocular or sub-Tenon corticosteroid or immunosup-ressive therapy (as monitored by a rheumatologist). Allatients signed an informed consent after detailed infor-ation about the limited experience, potential side effects,

nd the off-label usage of the drug.Best-corrected visual acuity (BCVA) was assessed using either

arly Treatment Diabetic Retinopathy Study (ETDRS) ornellen charts (half-and-half) and listed as logarithm ofinimal angle of resolution (logMAR) equivalents. Re-

reatment was done when there was recurrent activityvaluated by funduscopy, fluorescein angiography (leakage,rowth of CNV), or optical coherence tomography exam-nation. Differences between final and initial BCVA orentral foveal thickness (CFT) were tested using pairedtudent t test. For small sample size comparisons, nonpara-etric tests were used. Further associations were performed

sing one-way analysis of variance (ANOVA) or �2 testor continuous and categorical variables, respectively. Allnalysis was conducted using SPSS 13.0 statistical packageSPSS Inc, Chicago, Illinois, USA), and a P value lesshan .05 was considered significant.

RESULTS

INETY-NINE CONSECUTIVE EYES OF 96 PATIENTS, 33 MALE

nd 63 female (78 White, 9 Asian, 8 Hispanic, and 1lack) with a mean age of 39 years, were examined ataseline and followed up between 6 months and 24 monthsTables 1 and 2). The right eye was involved in 55 subjectsnd the left in 44 subjects (3 patients having bilateralisease). Uveitis was active in 26 eyes at the time of oculareovascularization. Forty-one patients (44 eyes) were tak-

ng oral, periocular, or intraocular corticosteroids or othermmunosuppressive agents. Thirty-three eyes received 0.1l (2.5 mg) of intravitreal bevacizumab and 66 eyes

eceived 0.05 ml (1.25 mg). The diagnosis was punctatenner choroidopathy (23), multifocal choroiditis withanuveitis (19), ocular histoplasmosis (13), idiopathic12), serpiginous choroiditis (9), Vogt-Koyanagi-Haradaisease (6), ocular toxoplasmosis (5), Eales disease (4),

sarcoidosis (2), sympathetic ophthalmia (2), tuberculosis

INFLAMMATORY OCULAR NEOVASCULARIZATIONOL. 148, NO. 2 311

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2), acute placoid pigment epitheliopathy (1), and bird-hot choroiditis (1).

Mean size of CNV was 1.3 disc diameters [DD] (range,.25 to 5). CNV was uniformly classic in type, subfoveal in9 eyes, juxtafoveal in 38 eyes, and peripapillary in 6 eyes,ith ocular new vessels of disc or elsewhere in 6 eyes. CNV

esponse following injection of bevacizumab was completeegression in size in 49 eyes, partial regression in size in 25yes, and no regression in size in 15 eyes (7 had absence ofeakage and 8 persistence of leakage). There was extensiveapillary nonperfusion in eyes with NVD/E (6 had NVD/End 4 CNV could not be graded because fluorescein wasot done after injection of Avastin).A total of 81 eyes had the 6-month follow-up data

ecorded. Mean BCVA of these 81 eyes improved fromaseline 0.67 (6/28 or 20/94) (standard deviation [SD],.46) to 0.43 (6/16 or 20/54) (SD, 0.41) (P � .001), a gainf 2.4 lines. BCVA improved 1 to 3 lines in 27 eyes33.3%), 4 to 6 lines in 14 eyes (17.3%), and more than 6ines in 12 eyes (14.8%). Function was unchanged in 14yes (17.3%) and worsened in 14 eyes (17.3%) (0 to 3 linesn 10 eyes, 4 lines or more in 4 eyes). Paired comparisonsevealed significant central foveal flattening at 6 months of8 �m (P � .001) after a mean of 2.0 injections.

Ninety-five eyes completed the 12-month follow-up.ean BCVA in these 95 eyes improved from baseline 0.65

6/27 or 20/90) (SD, 0.43) to 0.40 (6/15 or 20/50) (SD,.37) (P � .001), a gain of 2.5 lines. BCVA improved 1 tolines in 36 eyes (37.9%), 4 to 6 lines in 18 eyes (18.9%),

nd more than 6 lines in 15 eyes (15.8%). Function wasnchanged in 12 eyes (12.6%). BCVA worsened in 14 eyes14.7%) (0 to 3 lines in 6 eyes, 4 lines or more in 8 eyes).aired comparisons revealed significant central foveal flat-

TABLE 2. Visual Outcome (Expressed as Logarithm of MinimFoveal Thickness (Expressed in �m) After Intravitreal Beva

Intervals

Variables Baseline 6-

Number of eyes 99 81

Number of intravitreal bevacizumab injection,

mean � SD (range)

0 2.0 �

BCVA, mean � SD 0.65 � 0.44 0.43 �

Lines of visual improvement from baseline N/A 2

Difference in BCVA from baseline by paired

comparison, mean � SD

N/A 0.24 �

P valuea N/A

Central foveal thickness, mean � SD 338 � 87 257 �

Difference in central foveal thickness from

baseline by paired comparison,

mean � SD

N/A 78 �

P valuea N/A

BCVA � best-corrected visual acuity; SD � standard deviation.aUsing paired Wilcoxon nonparametric test and paired compariso

ening at 12 months of 85 �m (P � .001) after a mean of (

AMERICAN JOURNAL OF12

.3 injections. Visual improvement did not correlate withize or location of CNV, presence of active uveitis, intakef immunosuppressive therapy, or disease category. Visualmprovement correlated with the angiographic regressionattern. Mean visual improvement was 3 lines in the groupith complete regression (0.029 logMAR improvement), 3

ines in the group with partial regression (0.304 logMARmprovement), and no improvement in the no-regressionroup (0.010 logMAR improvement) (P � .037). Theumber of injections at 1 year increased significantly with

ncreasing age (P � .043) and with the no-regressionattern (P � .001), but did not relate to the dosage (2.5g vs 1.25 mg bevacizumab).Forty-six eyes had 18-month follow-up. Mean BCVA in

hese 46 eyes improved from baseline 0.62 (6/25 or 20/84)SD, 0.44) to 0.37 (6/14 or 20/47) (SD, 0.41) (P � .001),gain of 2.5 lines. BCVA improved 1 to 3 lines in 12 eyes

26.1%), 4 to 6 lines in 9 eyes (19.6%), and more than 6ines in 8 eyes (17.4%). Function was unchanged in 10yes (21.7%). BCVA worsened in 7 eyes (15.2%) (0 to 3ines in 2 eyes, more than 3 lines in 5 eyes). Using pairedample t test, the mean CFT decreased by 112.7 �m fromaseline (P � .043) after a mean of 3.0 injections. Pairedomparisons revealed significant central foveal flatteningt 18 months of 90 �m (P � .003) after a mean of 3.0njections.

So far, 27 eyes reached 24 months of follow-up. MeanCVA improved from baseline 0.54 (6/22 or 20/70) (SD,.38) to 0.32 (6/13 or 20/42) (SD, 0.32) at 2 years (P �017), a gain of 2.2 lines. BCVA at 2 years improved 1 to

lines in 5 eyes (18.5%), 4 to 6 lines in 4 eyes (14.8%),nd more than 6 lines in 7 eyes (25.9%). Function wasnchanged in 6 eyes (22.2%). BCVA worsened in 5 eyes

gle of Resolution Best-Corrected Visual Acuity) and Centralab for Inflammatory Ocular Neovascularization at Various

e Study

12-Month 18-Month 24-Month

95 46 27

to 5) 2.3 � 1.8 (1 to 12) 3.0 � 2.6 (1 to 14) 3.6 � 4.2 (1 to 21)

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aired comparisons revealed significant central foveal flat-ening at 24 months by 77 �m (P � .022) after a mean of.6 injections.There were no dropouts in the present study: shorter

ollow-ups corresponded to more recently recruited sub-ects. The present therapeutic modality’s being very recentade the follow-up period relatively short. The longest

ollow-ups were in 4 patients: 1) 3 years follow-up in aatient with peripapillary CNV related to toxoplasmosis,ith BCVA improving from 6/10 (20/32) to 6/6 (20/20)fter 3 injections of bevacizumab; 2) 2.5 years follow-up inpatient with subfoveal CNV related to punctate inner

horoidopathy, with BCVA improving from 6/60 (20/200)o 6/7 (20/22) after a single bevacizumab injection; 3) 2.5ears follow-up in subfoveal CNV related to ocular his-oplasmosis, with BCVA from 6/7 (20/22) to 6/7 (20/22)fter a single injection of bevacizumab; 4) 2.5 yearsollow-up in peripapillary CNV related to Vogt-Koyanagi-arada, with BCVA improving from 6/60 (20/200) to 6/7

20/22) after 10 injections.No injection-related complications such as cataract,

etinal detachment, endophthalmitis, or exacerbation ofveitis were reported. Five eyes had possible bevacizumab-elated complications. One patient with idiopathic uveitisnd subfoveal CNV had mild ocular hypertension afterntravitreal bevacizumab. Another patient had macularemorrhage immediately after intravitreal injection ofevacizumab for juxtafoveal CNV from punctate innerhoroidopathy. Four eyes had submacular fibrosis (presentn 1 before the injection and in 3 after the injection). Oneatient with long-standing peripapillary CNV related toogt-Koyanagi-Harada developed submacular fibrosis that

ncreased following intravitreal injections. Three eyes withubfoveal CNV (2 from sympathetic ophthalmia and 1rom Vogt-Koyanagi-Harada) developed subretinal fibrosisnd all had no regression of CNV after intravitrealnjections.

Subgroup analysis was also performed. Analysis of theultifocal choroiditis group revealed significant improve-ent in visual acuity (VA) at 6 months (P � .009), at 12onths (P � .05), and at 18 months (P � .012), with

ignificant decrease in foveal thickness throughout (P �014 at 6 months, P � .009 at 12 months, and P � .034 at8 months). Analysis of the ocular histoplasmosis groupevealed significant visual improvement at 12 months (P �046). Analysis of the punctate inner choroidopathy groupevealed significant visual improvement at 6 months (P �03) and at 12 months (P � .002), with significantecrease in CFT throughout (P � .012 at 6 months, P �043 at 12 months). Analysis of the idiopathic groupevealed significant visual improvement at 6 months (P �024) and at 12 months (P � .045). Analysis of theoxoplasmosis group revealed significant visual improve-ent at 12 months (P � .043). Analysis of the serpiginous

horoiditis group revealed borderline significance in visual

mprovement at 12 months (P � .058). Analysis of the w

INFLAMMATORY OCULAR NOL. 148, NO. 2

ubfoveal group revealed significant visual improvement atmonths (P � .001), 12 months (P � .001), and 18onths (P � .045). Significant decrease in CFT was

resent at 6 months (P � .002) and 12 months (P � .003).nalysis of the juxtafoveal group revealed significant

isual improvement at 6 months (P � .026), 12 monthsP � .006), and 18 months (P � .017). Significantecrease in CFT was present at 6 months (P � .002), 12onths (P � .003), and 18 months (P � .028).The angiographic regression pattern after intravitreal

evacizumab correlated with presence of active uveitis (P �003) (complete regression occurred in 26.9% of eyes withctive uveitis vs 63.2% of eyes with inactive uveitis), andith size of the CNV (P � .05): mean size of CNV was.10 DD in eyes with complete regression, 1.34 DD in eyesith partial regression, and 1.76 DD in eyes with no

egression. The angiographic regression pattern correlatedignificantly with the primary disease: no regression wasound in 31.6% of eyes with multifocal choroiditis vs 4.3%f eyes with punctate inner choroidopathy and none ofyes with ocular histoplasmosis (P � .027). Completeegression correlated with younger age. The angiographicegression pattern did not correlate with location of CNVr intake of immunosuppressive therapy.Four eyes with NVD/E from Eales disease and 2 eyes

ith idiopathic inflammatory NVD/E had complete regres-ion in 3 eyes and partial regression in 3 eyes withtabilization of the retinopathy and vision in all 6 eyesollowing intravitreal bevacizumab throughout the follow-p: 6 months (6 eyes; single injection in 5 eyes and 2njections in 1 eye), 12 months (6 eyes; single injection ineyes and 2 injections in 1 eye), 18 months (5 eyes; single

njection each), and 24 months (2 eyes; single injectionach).

DISCUSSION

NFLAMMATORY OCULAR NEOVASCULARIZATION AFFECTS

elatively young patients and can lead to severe visual loss.he natural history of subfoveal CNV in ocular histoplas-osis,9 punctate inner choroidopathy,10 multifocal cho-

oiditis with panuveitis, Vogt-Koyanagi-Harada disease,11

nd other inflammatory chorioretinal disorders has beenery guarded. In a natural history study of subfoveal CNVn 74 patients with ocular histoplasmosis, final visualesults of 6/30 (20/100) or worse were found in 77% of theatients followed at 36 months.9

Long-term results of photodynamic therapy in inflamma-ory ocular neovascularization have been published.12–16

arodi and associates14 found stabilization of vision at 1 yearnd 2 years after photodynamic therapy for juxtafovealNV in 7 patients with multifocal choroiditis. Nowilati

nd associates15 found stabilization of vision in 6 patients

ith Vogt-Koyanagi-Harada followed for a mean of 23

EOVASCULARIZATION 313

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onths. At the 24-month examination, median improve-ent from baseline in VA of the 22 patients evaluated was

.2 lines for subfoveal CNV after photodynamic therapy inatients with ocular histoplasmosis.12

Intravitreal injections of vascular endothelial growthactor (VEGF) inhibitors represent the first specific treat-ent approach actually influencing the pathogenic path-ay of CNV17–22 and NVD/E23–27 formation. Shimadand associates28 described 14 patients with multifocalhoroiditis with panuveitis (8 eyes) or punctate innerhoroidopathy (6 eyes) who underwent surgical excision ofNV. All 14 excised CNVs expressed VEGF by immuno-istochemistry. Chan and associates17 used bevacizumab toreat 4 patients with punctate inner choroidopathy andNV. At the 6-month follow-up, median VA improved

rom 6/19.5 (20/65) to 6/9.6 (20/32). In another study,chadlu and associates19 treated 28 eyes with CNV sec-ndary to ocular histoplasmosis. Baseline mean BCVA was.65 (20/88) and improved to a final mean BCVA of 0.4320/54) (2.2 lines improvement) over a mean follow-up ofmonths with an average of 1.8 intravitreal injections.Adán and associates20 described 9 patients with various

nflammatory CNV treated with bevacizumab injections.NV resolved in all affected eyes with BCVA improving

n 88.8% of eyes over a mean follow-up of 7.1 monthsrange, 6 to 10 months), and after a mean of 1.3 injections.edian acuity improved from 6/30 (20/100) to 6/12

20/40) (statistically not significant), while foveal thick-ess decreased significantly by 140 �m. Tran and associ-tes29 described 10 patients with uveitis and CNV followedor a mean of 7.5 months. CNV was subfoveal in 8 cases anduxtafoveal in 2 cases. After a mean number of injectionsf 2.5, logMAR BCVA improved significantly from 0.6220/55) to 0.45 (20/40) at 1 month, then remained stableuring the follow-up. Mean central macular thickness wasignificantly reduced from baseline 326 �m to 267 �m atast visit. Leakage from inflammatory CNV was stopped in

eyes and decreased in 7 eyes.Chang and associates30 described 12 patients with mul-

ifocal choroiditis and CNV that had visual improvementno further details could be retrieved in this combinederies). Fine and associates31 described 5 patients withultifocal choroiditis and CNV followed for 6 months thatad visual improvement in 4 patients and visual worsening

n 1 patient after the development of a retinal pigmentpithelial tear.

Küçükerdönmez and associates23 described a patientith broad retinal neovascularization from Eales disease

hat did not regress after adequate photocoagulation. Oneeek after bevacizumab injection, fluorescein angiographyemonstrated dramatic regression of retinal neovascular-zation. After 12 months, BCVA was improved and no

igns of recurrence were observed. Kumar and Sinha24 n

onduct of study (A.M.M.); statistical analysis (A.M.S.); collection of data (

AMERICAN JOURNAL OF14

reated with a single injection 1 patient with Eales diseaseith resolution of NVD/E over 4 months of follow-up. The

imilar sustained and complete response to therapy in Ealesisease we saw in our series (1 injection caused regressionf NVD/E for 6 months in 1 eye, 18 months in 1 eye, and4 months in 2 eyes) may be explained by the massiveEGF expression in Eales disease and other vasculiti-es,25–27 and the stabilizing effect of panretinal photoco-gulation performed in these eyes.

In the present study, visual improvement correlatedignificantly with the angiographic regression pattern afterntravitreal bevacizumab. Eyes with either complete orartial regression pattern had a mean improvement of 3ines. There was no visual improvement in eyes thatemonstrated absence of anatomic regression. The angio-raphic regression pattern after intravitreal bevacizumaborrelated positively with presence of active uveitis, size ofhe CNV, and the primary disease. No anatomic regressionas found in 31.6% of eyes with multifocal choroiditis vs.3% of eyes with punctate inner choroidopathy and nonef eyes with ocular histoplasmosis. Final acuity may beeopardized by submacular fibrosis, which was detected in 2yes with sympathetic ophthalmia and 2 eyes with Vogt-oyanagi-Harada. Aggressive inflammatory CNV, like

hose in Vogt-Koyanagi-Harada and sympathetic ophthal-ia, require close observation, systemic immunomodula-

ion, and frequent intravitreal bevacizumab injections.his is in contrast to other forms of inflammatory CNVnd NVD/E that had prompt regression and required aingle or a few injections over the 2-year follow-up. Alsoe found significant visual improvement and significantentral foveal flattening after intravitreal bevacizumab inubgroup analyses of punctate inner choroidopathy, mul-ifocal choroiditis with panuveitis, ocular histoplasmosis,ubfoveal CNV group, and juxtafoveal CNV group. This isdditional evidence for the efficacy of bevacizumab.

Fewer injections were needed in inflammatory CNVompared to eyes with age-related CNV because of: 1)nflammatory CNV being classic; 2) inflammatory CNVeing small in size; 3) angiostatic effect of periocular orystemic corticosteroids in inflammatory CNV; and 4)ounger age of subjects with inflammatory CNV and aenerally healthy retinal pigment epithelium. Intravitrealevacizumab injections maintained VA and foveal flatten-ng throughout the 2-year period in the present study witho signs of tachyphylaxis. The earlier findings based onmall case series and followed for a short period as well ashe findings in this large case series of inflammatory CNVor NVD/E) with follow-up of 2 years suggest that anti-EGF treatment may be superior to previous therapies, with

n improvement of more than 2 lines in BCVA and signifi-ant foveal flattening in a wide variety of inflammatory ocular

eovascularization with no major complications.

HE AUTHORS INDICATE NO FINANCIAL SUPPORT OR FINANCIAL CONFLICT OF INTEREST. INVOLVED IN DESIGN AND

all authors); management, analysis, and interpretation of the data (all

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uthors); and preparation, review, and approval of the manuscript (all authors). We obtained Institutional Review Board approval of the research fromhe following: the American University of Beirut, Beirut, Lebanon; University of Puerto Rico, San Juan, Puerto Rico; the Arevalo-Coutinho Foundationor Research in Ophthalmology, San Bernardino, Caracas, Venezuela; Instituto de Cirugia Ocular, San Jose, Costa Rica; Universidade Federal de Sãoaulo, Instituto da Visão, São Paulo, Brazil; Asociación para Evitar la Ceguera en México, Mexico City, Mexico; Fundacion Oftalmologica Nacional,niversidad del Rosario, Bogota, Colombia; Fundacion Conde Valenciana, Mexico City, Mexico; Clínica Ricardo Palma, Lima, Peru; Hospitalniversitario Austral, Buenos Aires, Argentina; Universidade Federal de Goiás, Goiânia, Brazil; Hospital de Olhos de Araraquara, and the Universidade

e São Paulo, São Paulo, Brazil; Fundacion Oftalmologica Los Andes, Santiago de Chile, Chile; Universidad de Buenos Aires, Buenos Aires, Argentina;niversity of Tuebingen, Tuebingen, Germany; Hospital Clinic de Barcelona, Universidad de Barcelona, Barcelona; Narayana Nethralaya, Bangalore,

ndia; Groupe Hospitalier Pitié Salpêtrière, Paris, France; and the University of Heidelberg, Heidelberg, Germany. The study was registered in theational Clinical Trials (NCT 00645697).The authors acknowledge the contribution of cases by the Pan-American Collaborative Retina Study Group.

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Biosketch

r J. Fernando Arevalo is a Professor and Chairman of the Clinica Oftalmologica Centro Caracas in Venezuela. He is aember of the Pan-American Association of Ophthalmology Educational Committee. Dr Arevalo has more than 100

ublications and dozens of chapters written in the field of retinal diseases. He received innumerable awards from variousnternational societies.

INFLAMMATORY OCULAR NEOVASCULARIZATIONOL. 148, NO. 2 316.e1

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Biosketch

r Ahmad M. Mansour is a Professor at the American University of Beirut and Chairman of the Eye Department at Raficariri Eye Hospital, Beirut, Lebanon. He is a fellow of the American Academy of Ophthalmology. Dr Mansour has more

han 100 publications and dozens of chapters written in the field of retinal diseases and ophthalmic pathology. He is theecipient of several local and international awards.

AMERICAN JOURNAL OF OPHTHALMOLOGY16.e2 AUGUST 2009