JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICSVolume 23, Number 5, 2007© Mary Ann Liebert, Inc.DOI: 10.1089/jop.2007.0036

Role of Intravitreal Bevacizumab in Neovascular Glaucoma

MOATAZ E. GHEITH,1 GHADA A. SIAM,1 DANIELA S. MONTEIRO DE BARROS,1SUNIR J. GARG,2 and MARLENE R. MOSTER1

ABSTRACT

We report on the effect of intravitreal bevacizumab (IVB) for the treatment of neovascularglaucoma (NVG). A retrospective chart review of 6 consecutive cases of NVG was performed.The follow-up period was 3–19 months (average, 9.7 months). All patients received 1.25 mg(0.05 cc) of IVB followed by panretinal photocoagulation (PRP) approximately 1 week later.In all cases, there was a complete regression of iris and anterior chamber angle neovascular-ization. However, 2 eyes showed a recurrence of neovascularization; in 1 case, it recurred af-ter 3 months, and in the second, after 5 months. These patients received another IVB injec-tion followed by additional PRP, which resulted in the resolution of the recurrentneovascularization. Glaucoma was controlled with topical eye drops alone in patients whohad iris and angle neovascularization without peripheral anterior synechiae (PAS). However,patients with PAS at the time of presentation needed subsequent glaucoma surgery. Our studysuggests that IVB may be a valuable addition in the treatment of NVG by hastening the res-olution of anterior segment neovascularization, improving the results of glaucoma surgeries,and appears to give long-term control when used in combination with PRP.

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INTRODUCTION

ISCHEMIC RETINOPATHIES can cause new vesselgrowth on the iris surface and in the anterior

chamber angle that can lead to neovascular glau-coma (NVG). Dysregulation of vascular endothe-lial growth factor (VEGF), a mitogen specific forvascular endothelial cells, has been implicated in several ocular diseases, including diabeticretinopathy and exudative age-related maculardegeneration (AMD).1,2 Bevacizumab, a recombi-nant anti-VEGF, is approved by the Food andDrug Administration for the treatment of colo-rectal and lung cancer.3 Recently, several reports

regarding the efficacy of off-label use of intravit-real bevacizumab (IVB) for the treatment of neo-vascular AMD, macular edema,4–6 and neovas-cular glaucoma have been published.7–9 Whileencouraging, these early reports have been lim-ited by a relatively short follow-up. We sought toevaluate the longer term results from the use ofIVB for the treatment of NVG.

METHODS

We retrospectively reviewed the charts of 6consecutive patients with NVG who presented to

From 1The Glaucoma Service Department and 2The Retina Service of Wills Eye Institute, Thomas Jefferson Uni-versity, Philadelphia, PA.

The authors have no financial interest related to the material presented in this paper.

our institution. After reviewing the off-label na-ture and possible complications of this drug, allpatients gave written, informed consent. All pa-tients received 1.25 mg (0.05 cc) of IVB as an ini-tial treatment of NVG. Panretinal photocoagula-tion (PRP) was started approximately 1 weekafter the IVB injection. If the intraocular pressure(IOP) could not be controlled despite maximaltolerable medical treatment, a trabeculectomywith mitomycin C or shunt operation was per-formed. Details of the 6 cases are below, and aresummarized in Table 1.

CASE REPORTS

Case 1

A 53-year-old man with a 12-year history of di-abetes and an 8-year history of open-angle glau-coma (with a mean IOP of 15 mmHg with treat-ment) complained of decreased vision and severepain in his right eye. An examination of his righteye revealed a visual acuity of 20/400 and an IOPof 51 mmHg. Anterior segment examination andgonioscopy revealed corneal edema, and neovas-

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TABLE 1. SUMMARY OF CASES

Case 1 Case 2 Case 3 Case 4 Case 5 Case 6

Age 53 83 50 63 63 82Gender Male Female Male Male Male FemaleDiabetes � � � � � �Vein occlusion � � � � � �Preexisting Glaucoma � � � � � �Mean IOP Pre-NVG 15 17 14 20 17 18

(mmHg)

At presentationVision 20/400 CF CF 20/60 CF HMIOP (mmHg) 51 44 38 36 36 37Neovascularization of iris � � � � � �Neovascularization of angle � � � � � �PAS at the angle � � � � � �Other ocular pathologies Cilioretinal artery � � � � �

occlusionPrevious ocular surgeries � Cataract � Vitrectomy Cataract �

extraction extraction1 week after IVB

Vision 20/400 CF CF 20/40 CF HMIOP 20 32 16 20 30 27Neovascularization of iris � � � � � �

and anglePAS at angle � � � � � �

Other proceduresPost-IVB

PRP � � � � � �Trabeculectomy � � � � � �Shunt � � � � � �Vitrectomy � � � � � �Cataract extraction � � � � � �

Duration between initial IVB 1 month 5 months 2 months 3 monthsand surgery

At end of follow-up:Vision 20/400 HM CF 20/40 HM CFIOP (mmHg) 16–20 17 18 16–19 18 11Neovascularization of iris � � � � � �

and angleSecond IVB injection � � � � � �Follow-up period 19 months 10 months 12 months 9 months 5 months 3 months

IOP, intraocular pressure; NVG, neovascular glaucoma; PAS, peripheral anterior synechiae; PRP, panretinal pho-tocoagulation; IVB, intravitreal bevacizumab; CF, counting fingers; HM, hand movement.

cularization of the iris (NVI) and of the angle(NVA). A fundus examination showed a centralretinal vein occlusion (CRVO), superior cilioreti-nal branch artery occlusion, and cystoid macularedema (CME). He was given an IVB injection.One (1) week later, the vision remained 20/400in the right eye. Complete regression of rubeosiswas seen, the IOP had decreased to 20 mmHg,and there was marked reduction in the CME. PRPof the right eye was performed. Through 19months of follow-up, his vision remained stableat 20/400, his IOP with topical treatment rangedfrom 16 to 20 mmHg, and there was no recur-rence of neovascularization.

Case 2

An 83-year-old woman presented with a 3-week history of eye pain and loss of vision in herright eye. Her history was remarkable for a 15-year history of diabetes and hypertension, a 13-year history of open-angle glaucoma (with amean IOP of 17 mmHg with treatment), andbilateral cataract extraction with posterior cham-ber intraocular lens (PC-IOL) implantation 12years ago. At presentation, her visual acuity wascounting fingers (CF) in her right eye, with anIOP of 44 mmHg. Anterior segment examinationand gonioscopy revealed mild corneal edema andflorid neovascularization of both the iris and theanterior chamber angle. A fundus examinationshowed a CRVO with neovascularization of thedisc (NVD). The patient received an intravitrealinjection of bevacizumab and was treated withIOP-lowering medications. One (1) week later,the cornea was clear, her vision remained CF, theIOP had decreased to 32 mmHg, and there was acomplete regression of the iris and angle neovas-cularization. PRP was performed in the right eye.Repeated gonioscopy revealed a closed anglewith peripheral anterior synechiae (PAS). HerIOP was 30 mmHg despite maximal tolerable top-ical therapy, so 1 month later, she underwent anuneventful placement of an Ahmed valve shunt(New World Medical, Inc., Rancho Cucamonga,CA). One (1) month postoperatively, the visionwas stable at hand movement, IOP was 16mmHg, and there was no anterior segment neo-vascularization. At the 2-month follow-up, therewas recurrent rubeosis and the IOP had increasedto 28 mmHg, so a second injection of IVB wasperformed, followed by an additional PRP, whichcaused a complete regression of the NVI/NVA

and resulted in a decrease in IOP to 17 mmHg.Her most recent follow-up 7 months after the ini-tial bevacizumab injection revealed stable handmotion vision, an IOP in the high teens, and awell-functioning valve shunt with no recurrentneovascularization.

Case 3

A 50-year-old man with a 14-year history of di-abetes presented with pain and photophobia inright eye. Examination of his right eye revealedvisual acuity of counting fingers and an IOP of38 mmHg. Anterior segment examination and go-nioscopy revealed both NVI and NVA. Fundusexamination revealed a CRVO in the right eyeand severe nonproliferative diabetic retinopathyin the left eye. IVB was injected into the right eye.One (1) week later, the vision remained countingfingers, but the anterior segment neovasculariza-tion had disappeared, and the IOP had decreasedto 16 mmHg. PRP was performed in the right eye.The condition remained stable for 5 months, andthen the patient returned with decreased visionin the right eye. An examination revealed a re-currence of iris neovascularization and vitreoushemorrhage. Another bevacizumab injection wasperformed, followed 2 weeks later by a pars-plana vitrectomy with fill-in PRP. One (1) weekpostoperatively, the NVI/NVA had regressed,the vision was counting fingers, and IOP was 18mmHg with topical medications. Follow-up 6months later showed a stability of the condition.

Case 4

A 63-year-old man with a history significant fordiabetes, had a 3-year history of open-angle glau-coma (with a mean IOP of 20 mmHg with treat-ment), and a more recent history of vitrectomyfor vitreous hemorrhage (caused by a flat retinaltear) in the left eye 3 months prior to returningto our clinic with decreased vision in the left eye.On examination, the vision in the left eye was20/60 and the IOP was 36 mmHg with topicaltreatment. Both NVI and NVA were present. Thepatient received an IVB injection. One (1) weeklater, the vision was 20/40 and IOP was 20 mmHgwith topical treatment, and the NVI/NVA haddisappeared. The patient received PRP. At the 9-month follow-up, the vision remained stable at20/40, the IOP ranged from 16 to 19 mmHg ontopical glaucoma medications, and there was norecurrent anterior segment neovascularization.

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Case 5

A 63-year-old man presented with decreased vi-sion in the right eye. He had a medical history ofdiabetes, renal disease, and hypertension as wellas an ocular history of bilateral open angle glau-coma (with mean IOP with treatment of 17 mmHgin the right eye and 14 mmHg in the left eye) andbilateral cataract extraction with PC-IOL. At pre-sentation, the visual acuity in the right eye was CFand the IOP was 36 mmHg. Anterior segment ex-amination and gonioscopy revealed NVI, NVA,and PAS. A fundus examination revealed prolif-erative diabetic retinopathy (PDR). IVB was in-jected into the right eye. One (1) week later, norubeosis or angle neovascularization was presentand the IOP was 30 mmHg. PRP was performedto the right eye. Two (2) months later, a subscleraltrabeculectomy with mitomycin C was done for apersistently elevated IOP despite maximal tolera-ble medical therapy. Postoperatively, the visionwas hand motion with an IOP of 18 mmHg. Five(5) months after the initial bevacizumab injection,the IOP was well controlled without topical drops,and there was no recurrent neovascularization.

Case 6

An 82-year-old woman with a history signifi-cant of diabetes, hypertension, and narrow angleglaucoma in the right eye (with mean IOP of 19mmHg with treatment) presented with decreasedvision and pain in her right eye. Her visual acu-ity was hand motion with an IOP of 37 mmHg.Anterior segment examination and gonioscopyrevealed a 3� cataract, NVI and NVA with PAS,and a patent Nd:YAG peripheral iridotomy. Herfundus examination showed a CRVO. An IVB in-jection was performed followed by PRP. One (1)week later, her vision was hand motions, the IOPwas 27 mmHg, and the NVI and NVA had re-gressed completely. The PAS persisted. Despitemaximal tolerable medical treatment, the IOP re-mained in the high twenties, so 3 months later,the patient underwent a cataract extraction withPC-IOL and trabeculectomy with mitomycin C.Postoperatively, her vision was CF and the IOPwas 11 mmHg. There was no recurrence ofNVI/NVA during the 3 month follow-up period.

DISCUSSION

The traditional treatment of neovascular glau-coma includes panretinal laser photocoagulation,

ocular antihypertensive medications, glaucomadrainage surgeries, and cyclodestructive proce-dures. However, neovascular glaucoma can be arefractory glaucoma that may not be controlledby any of these means.10 A pharmacologic treat-ment for neovascularization may be an alterna-tive or adjunctive treatment for ischemic oculardisorders, including neovascular glaucoma.11 Inour cases, we used a combination of IVB and PRP.In all of these cases, there was a complete re-gression of iris and anterior chamber angle neo-vascularization. Our results were similar to pre-vious reports.7–9,12 Recurrence of INV after anIVB injection was previously reported.13,14 Two(2) of our cases showed a recurrence of anteriorsegment neovascularization, after 3 months in 1case and after 5 months in the second case. Bothof these patients had ischemic central vein occlu-sions and both had received extensive PRP in theaffected eye. These patients received another in-travitreal bevacizumab injection, followed by ad-ditional PRP, which resulted in a resolution of therecurrent neovascularization. It is possible thatthese patients had inadequate initial PRP, and theneovascularization recurred when the effect ofthe bevacizumab wore off. The initial PRP wasperformed with care taken to apply laser spotsapproximately three quarters of a burn widthapart, starting at the vascular arcades, and takenout to the ora serrata. In cases of rubeosis in whichbevacizumab is not used, regression of anteriorsegment neovascularization is the main indicatorthat adequate PRP has been performed. In theseeyes, that indicator disappears before the PRPwas initiated; thus, the amount of PRP may havebeen underestimated. The follow-up period inour study ranged from 3 to 19 months (average,9.7), which is considerably longer than the previ-ous studies.

We did not detect inflammation in our patientsfollowing the injection of bevacizumab. Pieram-ici and colleagues reported anterior uveitis afteran intravitreal injection of bevacizumab15; how-ever, in their report, the inflammation occurredafter the 4th injection. In our cases, 2 or less in-jections were needed to achieve neovascular re-gression.

Trabeculectomy alone and Ahmed shunt oper-ations for neovascular glaucoma have low suc-cess rates, probably due to excessive intra-or post-operative inflammation and bleeding caused byneovessels.16,17 Jonas and colleagues reported awell-functioning bleb after a filtering glaucoma

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operation combined with IVB.18 In our study,glaucoma was controlled with topical eye dropsalone in patients who had iris and angle neovas-cularization without PAS. However, patients thathad neovascularization of the angle with PAS atthe time of presentation needed subsequentsurgery to control glaucoma (e.g., trabeculec-tomy, shunt, or vitrectomy). In those patients,good control of IOP was maintained through themost recent follow-up. Furthermore, intra- orpostoperative complications commonly seen inneovascular glaucoma surgeries, such as bleed-ing and inflammation, did not occur.16,17,19,20

CONCLUSIONS

Our study suggests that IVB may be a valuableaddition in the treatment of neovascular glau-coma by hastening the resolution of anterior seg-ment neovascularization, improving the resultsof glaucoma surgeries, and it appears to givelong-term control when used in combination withPRP. However, continued vigilance is needed tomonitor patients for recurrent anterior segmentneovascularization. If this occurs, the eyes mayrespond well to an additional IVB injection fol-lowed by fill-in PRP.

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Received: April 2, 2007Accepted: June 19, 2007

Reprint Requests: Moataz E. Gheith840 Walnut Street, Suite 1110

Philadelphia, PA 19107

E-mail: mgheith@hotmail.com

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