ANTERIOR SEGMENT ISCHEMIA WITH RUBEOSIS IRIDIS AFTER A CIRCULAR BUCKLING OPERATION TREATED SUCCESSFULLY WITH AN INTRAVITREAL BEVACIZUMAB INJECTION: A CASE REPORT AND REVIEW OF THE LITERATURE

JANSSENS K, ZEYEN T, VAN CALSTER J

ABSTRACT ly detection of rubeosis iridis. This report demon- strates the rapid resolution of rubeosis iridis on Purpose: To report a case of anterior segment ischemia fluorescein angiography after a second intravitreal in- (ASI) with rubeosis iridis after circular buckling sur- jection of bevacizumab. How long this regression will gery in a highly-myopic patient which was success- persist is unknown and repeated injections of fully treated with a second intravitreal bevacizumab bevacizumab may be necessary if rubeosis re- injection. appears. Methods: Case report and review of the literature. KEYWORDS Discussion: ASI is a rare but potentially serious com- plication of posterior segment surgery. Finally it leads Anterior segment ischemia (ASI); rubeosis iridis; to neovascular as a result of rubeosis iri- neovascular glaucoma (NVG); circular buckling dis. An encircling band can compromise anterior seg- surgery; intravitreal bevacizumab (IVB); iris ment circulation in different ways: by manipulation fluorescein angiography. or disinsertion of the recti muscles, by occlusion of the vortex veins through compression or by changes in the blood supply of iris and . This pa- tient developed rubeosis iridis secondary to ASI. There was a remarkable regression of rubeosis iridis one month after a second intravitreal bevacizumab in- jection. Other case reports of bevacizumab use in neovascular glaucoma have shown clinical improve- ments of these patients, with control and reduction of the process. Conclusion: We describe a highly-myopic patient who developed ASI with rubeosis iridis after a cir- cular buckling operation. Slit-lamp examination and gonioscopy can show very little rubeosis iridis and can be misleading. Iris fluorescein angiography is the most sensitive technique for evaluation of iris vessel abnormalities and is of considerable value in the ear-

zzzzzz Submitted: July 04, 2011 Accepted: Aug 08, 2011

Bull. Soc. belge Ophtalmol., 319, 5-9, 2012. 5 INTRODUCTION We describe a highly-myopic patient who developed rubeosis iridis and NVG after a circular Anterior segment ischemia (ASI) is a rare but buckling operation and surgery. This potentially serious complication of posterior case demonstrates a remarkable and rapid re- segment surgery. Finally it leads to neovascu- gression of rubeosis iridis after a second intra- lar glaucoma (NVG) as a result of rubeosis iri- vitreal bevacizumab injection, confirmed by an dis. The studies of Tanaka et al. (1) and Tawara iris fluorescein angiography. et al. (2) concluded that ASI, even without retinal ischemia, can cause neovascularization of the CASE HISTORY iris in rabbits. Tanaka et al. also reported that ASI causes an elevated aqueous vascular en- This 57-year-old myopic woman had a retinal dothelial growth factor (VEGF) in accordance detachment of the left in 1997. She un- with the ischemic severity (1). derwent a vitrectomy with encircling band, sil- icone oil tamponnade and endolaser photoco- ASI after posterior segment surgery is not usu- agulation in the left eye. The silicone oil (tam- ally found in young, healthy patients (3-6). Pre- ponnade) was removed 5 months later but she disposing factors are detachment of the recti developed a secondary glaucoma in 1998 due muscles, arterial and venous compression by to residual oil emulsification. The IOP was un- the explant or encircling band and the use of der control with topical therapy. In 1998 she diathermy (7). Underlying systemic conditions underwent surgery of the left eye with such as generalized atherosclerosis, dysthy- a postoperative visual acuity of 20/100. In 2003 roid ophthalmopathy and hematologic disor- a bilateral recession (4.5 mm) of the external ders including anemia, increased hypercoagu- rectus muscle was performed for a decompen- lability or sickle cell disease/trait can increase sated . In 2009 the IOP was not any the risk for ASI (8). more under control medically and a Baerveldt Inhibiting the process by block- tube was implanted in the anterior chamber of ing VEGF is a promising strategy for the treat- the left eye. Six months later there was a good ment of anterior segment neovascularization IOP control, but rubeosis iridis was observed and NVG (9). Bevacizumab is a full-length hu- at gonioscopy. Fundus fluorescein angiography manized monoclonal antibody against vascu- was performed and did not reveal retinal is- lar endothelial growth factor type A. Case re- chemia. A carotid echography was done, but ports of bevacizumab use in NVG or anterior showed no significant stenosis. segment neovascularization have shown clini- cal improvements of these patients, with in- In December 2009 she presented at our clinic traocular pressure (IOP) control (10-13) and re- with a red and painful left eye. On examina- duction of the neovascularization process (14- tion the visual acuity was counting fingers and 15). the IOP was 45 mmHg. Slit-lamp biomicros- copy showed a , rubeosis iridis and a well- formed anterior chamber. In- direct fundoscopy was not possible, but echography showed no retinal detach- ment. The diagnosis of neovascular glaucoma was set and she was treated with oral and topical IOP lower- ing drugs. One day later the IOP was reduced to Fig. 1: Iris fluorescein angiography showed pathologic vessels in all quadrants of 12 mmHg. Transscleral re- the iris showing leakage within seconds. Biomicroscopy showed very little rubeosis tinal cryocoagulation of the iridis. The angiographic picture was taken after 28 seconds. 4 retinal quadrants was per-

6 gest that the anterior cili- ary arterial system supplies 70% to 80% of the anteri- or segment blood supply (16). Just posterior to the muscle insertions, the an- terior ciliary arteries devi- ate from the muscle belly and penetrate the to anastomose with the long posterior ciliary arteries. The Fig. 2: These pictures were taken one month after a second IVB injection. Iris fluo- venous drainage of the an- rescein angiography revealed only regular radial iris vessels and minimal leakage in terior segment takes place the superotemporal quadrant. Biomicroscopy showed no rubeosis iridis. The an- through the 4-6 vortex giographic picture was taken after 37 seconds. veins. Damage to the vortex veins, the anterior ciliary ar- formed three days later and an intravitreal be- teries and the long posterior ciliary arteries are vacizumab (IVB) injection was also given. On the most important factors in the development examination two months later the visual acu- of ASI. There are various ways in which the vas- ity was 25/100 and the IOP 14 mmHg. Slit- cularization can be endangered. lamp biomicroscopy showed very little rubeo- sis iridis (Figure 1, right). Iris fluorescein an- After strabismus surgery, the incidence of an- giography at that time revealed pathologic ves- terior segment ischemia is approximately 1 case sels in all quadrants of the iris showing leak- per 13,000 procedures (8). It is sometimes age within seconds (Figure 1, left). One month necessary to detach one or more of the recti after a second IVB injection, only regular radi- muscles and this will cause the anterior ciliary al iris vessels and minimal leakage in the su- arteries to drop out. The vertical recti muscles perotemporal quadrant were seen (Figure 2, are most dangerous in this connection because left). there are no compensating long posterior cili- ary arteries there. Patients who have under- DISCUSSION gone two-muscle vertical rectus manipulation, operations involving three or more extraocular We present a patient with anterior segment is- muscles or strabismus surgery following encir- chemia (ASI) after a circular buckling opera- cling buckling surgery are more likely to expe- tion and strabismus surgery. The anterior seg- rience significant anterior segment ischemia. ment is vascularized by the long posterior cil- iary arteries and short anterior ciliary arteries. An encircling band or explant can compromise Two long posterior ciliary arteries arise from the anterior segment circulation in various ways ophthalmic artery and course toward the ante- (8). First by manipulation or disinsertion of the rior segment within the sclera along the hori- recti muscles. In the past, scleral buckle appli- zontal meridians. The vessels supply approxi- cation often included disinsertion of one or more mately 30% of the blood flow to the anterior recti muscles. Even with contemporary surgi- segment (8). The anterior ciliary arteries, which cal techniques, ischemia can also arise from oc- arise from the muscular branches of the oph- clusion of the vortex veins through compres- thalmic artery, lie within the recti muscles. There sion. Finally, scleral buckling can cause chang- are two anterior ciliary arteries per muscle, the es in the arterial circulation. In an experimen- sole exception being the lateral rectus, which tal model using albino rabbits, an encircling carries only one. The one anterior ciliary artery band decreased perfusion of the iris and cili- to the lateral muscle is also unique in that it ary body (17). often arises from the lacrimal artery. These ar- teries supply the remainder of the arterial flow Panretinal photocoagulation (PRP) can cause to the anterior segment. Primate studies sug- closure of the choriocapillaris (18). The long

7 posterior ciliary arteries are larger choroidal ves- IVB for six patients with rubeosis iridis and re- sels and usually remain patent after PRP,how- fractory NVG (10). This treatment resulted in ever, an additional insult, such as intraopera- marked regression of anterior segment neovas- tive hypotension, may precipitate ASI. Rela- cularization and relief of symptoms in the first tively low systemic blood pressure combined 2 days. The study of Sugimoto et al. conclud- with increased intraocular pressure during scler- ed that a single IVB to with rubeotic glau- al depression, may facilitate closure of the long coma reduced the neovascularization in the hu- posterior ciliary arteries in patients treated with man iris surface, but could not eliminate com- the indirect laser ophthalmoscope. PRP may be pletely neovascularization in iris stroma (20). more likely to cause ASI if orbital pressure is This finding implies that the prevention of hy- high, because it may cause compression of the phema and fibrin formation based on slit-lamp vortex veins. examination can’t be predicted, even if neovas- cularization in iris surface seems to be elimi- There are also underlying systemic medical con- nated by a single dose of IVB (20). ditions that can predispose a patient to ASI. With the use of iris fluorescein angiography, Older age, generalized atherosclerosis, blood Grisanti et al. studied the effects of IVB on dyscrasias, hematologic disorders that increase neovascularization of the iris (21). They pre- serum viscosity, dysthyroid ophthalmopathy, sented a case series of six eyes in three pa- carotid artery disease and carotid cavernous si- tients who had NVG and rubeosis iridis due to nus fistula can place patients at risk for ASI (8). central retinal vein occlusion or proliferative di- The clinical presentation of ASI is diverse, can abetic and received 1.0 mg of IVB. be subtle and difficult to detect. Patients usu- They noted a decrease in iris fluorescein leak- ally present with mild pain and reduced visual age as early as 1 day after injection. Of the six acuity beginning 1 or 2 days after posterior seg- eyes, there was no regression at 1-month fol- ment- or strabismus surgery. Early signs in- low-up. The role of bevacizumab and length of clude a poorly reactive , episcleral vessel therapeutic benefit was explored by Gheith et dilatation, conjunctival chemosis, corneal oede- al (22). They presented a case series of six pa- ma, mild iritis, a fibrinoïd reaction, , tients with an average of 9.7 months of follow- rubeosis iridis and neovascularization of the an- up. Each patient received IVB followed by PRP terior chamber angle. Late findings include pos- one week later. All patients had a complete re- terior synechiae and iris atrophy, chronic iri- gression of iris and angle neovascularization. docyclitis, keratopathy, anterior cortical cata- However two patients had recurrence of rube- ract, hypotony and finally phthisis. osis iridis after 3 and 5 months, respectively. Our patient developed rubeosis iridis and NVG They received another injection of bevacizum- secondary to ASI. There was no retinal is- ab that eradicated the recurrent neovascular- chemia, nor did the carotid echography showed ization. The pharmacokinetics of bevacizumab a carotid artery stenosis. The history of encir- was further investigated by Bakri et al. They cling band- and strabismus surgery were con- found that the vitreous half-life of 1.25 mg IVB tributing factors. As only one horizontal mus- is 4.32 days in a rabbit eye (23). cle, the lateral rectus, was recessed with 4.5 mm in both the eyes, we conclude that the cir- CONCLUSION cular buckling procedure was the major cause of the ASI. We describe a highly-myopic patient who de- Our patient had remarkable regression of rube- veloped ASI with rubeosis iridis and NVG after osis iridis on iris fluorescein angiography one a circular buckling operation and strabismus month after the second IVB injection. Avery re- surgery. Slit-lamp examination and goniosco- ported a single case of rapid resolution of iris py can show very little rubeosis iridis and can and retinal neovascularization with the admin- be misleading. Iris fluorescein angiography is istration of IVB (19). Davidorf et al. reported the most sensitive technique for the evaluation similar results in a single patient with regressed of iris vessel abnormalities and is of consider- rubeosis iridis after a single injection of beva- able value in the early detection of rubeosis iri- cizumab (15). Iliev et al. described the use of dis. Our patient had remarkable regression of

8 rubeosis iridis on iris angiography one month (13) Chilov MN, Grigg JR, Playfair TJ − Bevacizu- after a second IVB injection. How long this re- mab (Avastin) for the treatment of neovascu- gression will persist is unknown and repeated lar glaucoma. Clin Experiment Ophthalmol injections of bevacizumab may be necessary if 2007; 35:494-496. rubeosis iridis reappears. (14) Batioglu F, Astam N, Ozmert E − Rapid im- provement of retinal and iris neovasculariza- tion after a single intravitreal bevacizumab in- REFERENCES jection in a patient with central retinal vein oc- clusion and neovascular glaucoma. Int Opht- (1) Tanaka T,Matsuo T,Ohtsuki H − Aqueous vascu- halmol 2008; 28:59-61. lar endothelial growth factor increases in anterior (15) Davidorf FH, Mouser JG, Derick RJ − Rapid im- segment ischemia in rabbits. Jpn J Ophthal- provement of rubeosis iridis from a single be- mol 1998; 42:85-89. vacizumab (Avastin) injection. 2006; (2) Tawara A, Kubota T, Hata Y, et al. − Neovas- 26:354-356. cularization in the anterior segment of the rab- (16) Wilcox LM, Keough EM, Connolly RJ, Hotte CE bit eye by experimental anterior ischemia. − The contribution of blood flow by the ante- Graefes Arch Clin Exp Ophthalmol 2002; rior ciliary arteries to the anterior segment in 240:144-153. the primate eye. Exp Eye Res 1980; 30:167- (3) Boniuk M, Zimmerman LE − Necrosis of the 174. iris, ciliary body and retina following scleral (17) Diddie KR, Ernest T − Uveal blood flow after buckling operations with circling polyethylene 360 degree constriction in the rabbit. Arch tubes. Trans Am Acad Ophthalmol Otolaryn- Ophthalmol 1980; 98:729-730. gol 1961; 65:671-693. (18) Wilson DJ, Green WR − Argon laser panretinal − (4) Freeman HM, Hawkins WR, Schepens CL photocoagulation for : scan- Anterior segment necrosis. An experimental ning electron microscopy of human choroidal study. Arch Ophthalmol 1966; 75:644-650. vascular casts. Arch Ophthalmol 1987; (5) Ryan SJ, Goldberg MF. Anterior segment ische- 105:239-242. mia following scleral buckling in sickle cell he- (19) Avery RL − Regression of retinal and iris neo- moglobinopathy. Am J Ophthalmol 1971; vascularization after intravitreal bevacizumab 72:35-50 (Avastin) treatment. Retina 2006; 26:352- − (6) Girard LJ, Beltranena F Early and late com- 354. plications of extensive muscle surgery. Arch (20) Sugimoto Y, Mochizuki H, Okumichi H, et al. Ophthalmol 1960; 64:576-584. − Effect of intravitreal bevacizumab on iris ves- − (7) Ansem RP, Bastiaensen LA Glaucoma follo- sels in neovascular glaucoma. Graefes Arch wing operations. Doc Opht- Clin Exp Ophthalmol 2010; 248:1601-1609. halmol 1987; 67:19-24. − − (21) Grisanti S, Biester S, Peters S, et al. Bartz- (8) Bronner G, Zarbin MA, Bhagat N Anterior Schmidt KU, for the Tuebingen Bevacizumab ischemia after posterior segment surgery. Opht- Study Group. Intracameral bevacizumab for iris halmol Clin North Am 2004; 17:539-43 rubeosis. Am J Ophthalmol 2006; 142:158- − (9) Bhisitkul RB Vascular endothelial growth fac- 160. tor biology: clinical implications for ocular trea- (22) Gheith ME, Siam GA, de Barros DS, et al. − tments. Br J Ophthalmol 2006; 90:1542- Role of intravitreal bevacizumab in neovascu- 1547 lar glaucoma. J Ocul Pharmacol Ther 2007; (10) Iliev ME, Domig D, Wolf-Schnurrbursch U, Wolf − 23:487-491. S, Sarra GM Intravitreal bevacizumab (Avas- − tin) in the treatment of neovascular glauco- (23) Bakri SJ, Snyder MR, Reid JM, et al. Phar- ma. Am J Ophthalmol 2006; 142:1054- ma cokinetics of intravitreal bevacizumab (Avas- 1056. tin). 2007; 114:855-859. (11) Kelkar AS, Kelkar SB, Kelkar JA, Nagpal M, Pa- til SP − The use of intravitreal bevacizumab in neovascular glaucoma: a case report. Bull Soc Belge Ophthalmol 2007; 303:43-45. zzzzzz − (12) Kahook MY, Schuman JS, Noecker RJ Intra- Adress for Correspondence: vitreal bevacizumab in a patient with neovas- K. JANSSENS cular glaucoma. Ophthalmic Surg Lasers Ima- UZ Leuven ging 2006; 37:144-146. email: janssens−[email protected]

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