Pseudophakic cystoid macular edema (CME) is one of the causes of decreased vision after complicated or uneventful cataract surgery.1 CME usually resolves spontaneously in approximately 90% of eyes, and only a small subset of patients suffer from permanent visual morbidity.2,3 However, phacoemulsification has significantly reduced the incidence of pseudophakic CME after uneventful surgeries.4,5
Considering the large number of patients undergoing phacoemulsification, this small percentage of patients represent a population large enough to search appropriate treatment strategies.2 Various treatment modalities including topical, systemic, periocular, and intraocular steroids; topical nonsteroidal antiinflammatory drugs; and systemic carbonic anhydrase inhibitors have been used with different success rates to treat pseudophakic CME.2,3
The exact etiology of pseudophakic CME remains unknown, but intraocular inflammation appears to play a key role in its development.6,7 Vascular endothelial growth factor (VEGF) has been shown to be associated with breakdown of the blood–retinal barrier and increased vascular permeability, thereby contributing to the development of macular edema.6,7
Ranibizumab is a recombinant humanized monoclonal murine antigen-binding fragment (Fab) antibody that binds to all isoforms of VEGF and has been used extensively for the treatment of wet age-related macular degeneration, diabetic macular edema, retinal vein occlusion, and myopic choroidal neovascularization.8 Its off-label intraocular injection has been widely used for treatment of different ocular diseases associated with neovascularization and increased vascular permeability.9 In this article, the effects of prophylactic use of ranibizumab injection after complicated phacoemulsification cases with posterior capsular rent (PCR) was analyzed.
Seven consecutive cases of PCR during phacoemulsification were enrolled in this study. Written consent was taken preoperatively, and preoperative consent regarding potential use of ranibizumab in case of cataract surgery complications was taken routinely from all cases. A meticulous preoperative evaluation was performed before scheduling phacoemulsification. Surgeries were performed under topical anesthesia. A 2.2 mm corneal incision was made. After continuous curvilinear capsulorrhexis and hydroprocedures, phacoemulsification was performed by direct chop technique in 6 cases and divide and conquer technique in 1 case.
In 3 cases, PCR resulted during cortical removal, where there was no posterior vitreous phase disturbance, and posterior chamber in-the-bag AcrySof IQ monofocal IOLs (Alcon) were implanted. After closure of the surgical wound with hydration, 0.05 mL of ranibizumab (REJUMAB) was injected intravitreally through pars plana route. In the remaining 4 cases, PCR occurred during phacoemusification chopping, and there was vitreous loss. Anterior vitrectomy was performed, and a 3-piece posterior chamber ciliary sulcus-fixated AcrySof IOL was implanted. Intravitreal ranibizumab was injected through pars plana route after ophthalmic viscosurgical device aspiration and wound hydration. In 1 case with vitreous loss, there was evidence of CME on optical coherence tomography (OCT), and a second dose of ranibizumab was injected after 1 month. Topical steroid and antibiotic eyedrops were prescribed for 2 weeks, and topical nonsteroidal antiinflammatory drug eyedrops were prescribed for 2 months postoperatively. Postoperative visual acuity was checked at each follow-up day, and OCT was performed postoperatively at 1 week and at monthly interval to check for central macular thickness. Intraocular pressure (IOP) was measured on each follow-up with noncontact tonometer (NT 350, NIDEK Co., Ltd.).
Of the 7 patients, 4 were women and 3 men. The mean age of the patients was 76 years, ranging from 56 to 82 years (Table 1). Cataract grading as per Lens Opacities Classification System III10 was NS2 in 2 cases, NS3 in 1 case, NS4 in 3 cases, and P5 in 1 case. First postoperative uncorrected visual acuity was 20/40 in 3 cases, 20/80 in 3 cases, and 20/120 in 1 case. There was no significant anterior chamber reaction.
The corrected distance visual acuity (CDVA) was checked at 2 weeks postoperatively, and it was 20/20 in 6 cases and 20/30 in 1 case. All 6 cases maintained CDVA throughout the follow-up period. CDVA of the seventh case deteriorated to 20/40 at 1 month, and his OCT report showed CME, and a second dose of injection was given. That patient achieved 20/30 CDVA after 2 weeks of second injection and thus, maintained the same throughout the follow-up period of 9 months. The mean preoperative IOP was 15 mm Hg (11 to 18 mm Hg) and mean first postoperative IOP was 13 mm Hg (10 to 16 mm Hg). OCT on first postoperative week was not significant in all the cases. However, in 4 cases, preoperative OCT was available, and there was no significant difference with postoperative OCT at 1 week. The mean thickness of central macula was 225 μm (195 to 315 μm) at 1 month postoperative period. In 1 case, second injection was given at 1 month postoperatively (Figure 1). The patient had vitreous loss during phacoemulsification, and anterior vitrectomy was performed and sulcus-fixated IOL implanted.
At the end of 3 months, the mean central macular thickness was 210 μm (190 μm to 265 μm) (Figure 2). There was no reduction of postoperative visual acuity in any case until the mean follow-up period of 9 months.
Pseudophakic CME is the most common cause for suboptimal visual outcome after cataract extraction procedures and represents today the most common cause of unexpected visual loss after uneventful cataract surgery.11 Risk factors of the development of CME after cataract extraction included several intraoperative complications such as posterior capsular rupture, vitreous loss, and vitreous incarceration into the incision site and anterior chamber.1 Vitreous loss, vitreous to the wound, iris incarceration in the wound, posterior capsule rupture, and Nd:YAG capsulotomy have all been reported to predispose to CME.1
Miltiadis et al. (1998) studied the effect of different factors on CME development after IOL implantation.11 He reported a 13% incidence of CME after extracapsular cataract extraction with intact posterior capsule, whereas, if the capsule was ruptured, the rate increased to 27%. Moreover, vitreous in the anterior chamber resulted in the appearance of CME in 33% of cases.
VEGF causes breakdown of the blood–retinal barrier and increased vascular permeability, contributing to the development of macular edema. Anti-VEGF12 with intravitreal bevacizumab has been shown to be effective in refractory pseudophakic CME. However, prophylactic use of the same is not reported in the literature. Biosimilar ranibizumab is a safe and cheaper alternative of biologic molecule. This case report shows safety and effectiveness of biosimilar molecule in prophylactic use for CME. However, further studies are necessary to prove its usefulness as prophylaxis.
WHAT WAS KNOWN
- Cystoid macular edema (CME) usually resolves spontaneously, and currently, no standardized protocol exists for the prophylaxis and management of pseudophakic CME because of lack of prospective randomized clinical trials. Therapeutic interventions are based on the proposed pathogenesis of edema, mainly inflammation and vitreous traction.
WHAT THIS PAPER ADDS
- Considering the prevalence of CME after complicated cataract surgeries, prophylactic use of ranibizumab during primary procedure can be an alternative treatment modality.
1. Flach AJ. The incidence, pathogenesis and treatment of cystoid macular edema following cataract surgery. Trans Am Ophthalmol Soc 1998;96:557–634
2. Benitah NR, Arroyo JG. Pseudophakic cystoid macular edema. Int Ophthalmol Clin 2010;50:139–153
3. Jacobson DR, Dellaporta A. Natural history of cystoid macular edema after cataract extraction. Am J Ophthalmol 1974;77:445–447
4. Henderson BA, Kim JY, Ament CS, Ferruflno-Ponce ZK, Grabowska A, Cremer SL. Clinical pseudophakic cystoid macular edema: risk factors for development and duration after treatment. J Cataract Refract Surg 2007;33:1550–1558
5. Loewenstein A, Zur D. Postsurgical cystoid macular edema. Dev Ophthalmol 2010;47:148–159
6. Miyake K, Ibaraki N. Prostaglandins and cystoid macular edema. Surv Ophthalmol 2002;47:S203–S218
7. Tolentino MJ, McLeod DS, Taomoto M, Otsuji T, Adamis AP, Lutty GA. Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate. Am J Ophthalmol 2002;133:373–385
8. Sharma S; RE-ENACT 2 Study Investigators Group2-23, Khan MA, Chaturvedi A. Multicenter, retrospective study (RE-ENACT 2) on the use of Razumab™ (world's first biosimilar ranibizumab) in wet AMD, DME, RVO and Myopic CNV. J Clin Exp Ophthalmol 2019;10:1–6
9. Khalil GF, Mohammad MP, Medhi M, Masih H, Nasrollah S. Intravitral bevacizumab for pseudophakic cystoid macular edema; a systematic review. J Ophthaimic Vis Res 2012;7:235–239
10. Chylack LT Jr, Wolfe JK, Singer DM, Leske MC, Bullimore MA, Bailey IL, Friend J, McCarthy D, Wu SY. The lens opacities classification system III. The Longitudinal Study of Cataract Study Group. Arch Ophthalmol 1993;111:831–836
11. Miltiadis KT, Chrysanthi T, Vasilios D, Aleksandra K, Ioannis P. Cataract Surgery. Edited by Zaidi FH. Cataractv Surgery. Edited by Zaidi FH. London, England: Intech Open. 2013. chapter 22, page 324
12. Barone A, Russo V, Prascina F, Delle Noci N. Short-term safety and efficacy of intravitreal bevacizumab for pseudophakic cystoid macular edema. Retina 2009;29:33–37