Secondary Logo

Journal Logo

Pseudophakic cystoid macular edema

Yonekawa, Yoshihiro; Kim, Ivana K.

Current Opinion in Ophthalmology: January 2012 - Volume 23 - Issue 1 - p 26–32
doi: 10.1097/ICU.0b013e32834cd5f8
CATARACT SURGERY AND LENS IMPLANTATION: Edited by Natalie Afshari
Free

Purpose of review Pseudophakic cystoid macular edema (PCME) is a common cause of visual impairment after cataract surgery. This article systematically reviews and discusses the epidemiology, risk factors, diagnosis, and treatment of PCME, with a focus on advances in the past 1–2 years.

Recent findings The incidence of PCME has declined with the advent of modern surgical techniques. Optical coherence tomography (OCT) has become an important adjunct to biomicroscopy and fluorescein angiography. PCME prophylaxis with topical nonsteroidal anti-inflammatory drugs remains unproven because long-term visual outcomes and comparative effectiveness studies are lacking. Chronic, refractory CME remains a therapeutic challenge, but investigational therapies with potential include corticosteroid intravitreal injections and implants, and intravitreal anti-vascular endothelial growth factor treatments. Few studies have assessed surgical options.

Summary There is currently a lack of well designed randomized clinical trials to guide the treatment of PCME.

Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA

Correspondence to Ivana K. Kim, MD, Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, MA 02114, USA. Tel: +1 617 573 3367; fax: +1 617 573 3678; e-mail: ivana_kim@meei.harvard.edu

Back to Top | Article Outline

INTRODUCTION

Pseudophakic cystoid macular edema (PCME), also known as Irvine–Gass syndrome, is the most common cause of unexpected visual loss after cataract surgery [1]. The advent of phacoemulsification and small incision cataract surgery has reduced the incidence of PCME, but the sheer volume of cataract surgery still makes PCME a prevalent morbidity. Substantial advances in the treatment and prophylaxis of PCME have not been made during the past two decades [2▪▪], but encouraging investigational treatments are emerging.

Back to Top | Article Outline

DEFINITION, INCIDENCE, AND COST

PCME is defined as angiographic (seen on fluorescein angiography) or clinical (associated with decreased visual acuity), and acute (within 6 months) or chronic (over 6 months). Optical coherence tomography (OCT) definitions have also been proposed [3].

The incidence of angiographic PCME is as high as 60% after intracapsular cataract extraction, compared with 15–30% after extracapsular extraction [1]. PCME after modern phacoemulsification as detected on OCT has ranged from 4 [4] to 11% [5], but as high as 41% [2▪▪]. The incidence of clinical PCME is much lower, and ranges from 0.1 to 2.35% [6,7▪]. Up to 80% of these symptomatic patients will experience spontaneous improvement by 3–12 months [2▪▪].

A cost-analysis study of 139 759 medicare beneficiaries who underwent cataract surgery found that total ophthalmic payments were 47% (US$1092) higher for those who developed PCME (P < 0.0001) [8].

Back to Top | Article Outline

PATHOPHYSIOLOGY

PCME pathogenesis is likely multifactorial, but inflammation caused by surgical manipulation appears to be the major cause. Inflammatory mediators break down the blood–aqueous and blood–retinal barriers, leading to increased vascular permeability [9▪]. Transudate accumulates in the outer plexiform and inner nuclear layers of the retina and microcysts coalesce into cysts [1]. Lamellar holes and subretinal fluid accumulation may also occur.

Box 1

Box 1

Back to Top | Article Outline

RISK FACTORS

Surgical complications that predispose eyes to PCME include vitreous loss, vitreous traction at incision sites, vitrectomy for retained lens fragments, iris trauma, posterior capsule rupture, intraocular lens (IOL) dislocation, early postoperative capsulotomy, and the use of iris-fixated or anterior chamber IOLs [1,10].

Eyes with diabetic maculopathy have a higher risk of developing PCME [8,11]. It may be difficult to distinguish PCME from progression of diabetic macular edema (DME). Cataract surgery was historically thought to worsen diabetic retinopathy, but recent studies may not support this theory [12,13]. Postoperative macular edema usually develops in those with a prior history of DME [14], which, if exists at the time of surgery, is unlikely to resolve spontaneously [15]. DME or severe diabetic retinopathy should therefore be adequately treated before undergoing cataract surgery.

Uveitis predisposes eyes to premature cataract formation, and cataract extraction in these patients carries a higher risk for complications. However, modern surgical techniques allows for IOL placement in well selected cases. A retrospective series of 108 eyes with various causes of uveitis demonstrated a 21% incidence of clinical PCME, with 74% achieving final visual acuity of 20/40 or better [16]. In a prospective cohort of 41 eyes with uveitis and 52 without uveitis, Belair et al.[4] demonstrated that the incidence of PCME on OCT at 3 months postoperatively was 8 and 0%, respectively (P = 0.08). Eyes treated perioperatively with oral corticosteroids had a sevenfold risk reduction (relative risk, 0.14; P = 0.05) . Uveitis should thus be tightly controlled preoperatively.

Henderson et al. [6] showed that retinal vein occlusion (RVO), epiretinal membrane, and prostaglandin analogs were also risk factors for PCME in a retrospective series of 1659 cataract surgeries. Miyake et al.[17] suggested in several studies that PCME may be induced by benzalkonium chloride, a preservative found in many glaucoma medications. One randomized clinical trial (RCT) of 80 patients demonstrated that glaucoma patients treated with prostaglandin analogs were more likely to develop angiographic PCME compared with patients randomized to placebo (P = 0.03) [18]. A case series of three eyes with pseudoexfoliation also described resolution of CME after discontinuation of latanoprost [19]. However, a retrospective comparative study of 1253 eyes showed that perioperative glaucoma medication was not associated with clinical PCME (P > 0.05) [20]. The results may have differed if angiographic PCME were the endpoint.

Back to Top | Article Outline

DIAGNOSIS

The incidence of clinical PCME peaks at approximately 4–6 weeks postoperatively. Most patients with clinical PCME will present with blurry vision, and biomicroscopy will show retinal thickening and loss of the foveal depression. Findings are best observed using a fundus contact lens, and red-free light may allow better visualization of cystic changes.

Fluorescein angiography findings include retinal telangiectasis, capillary dilatation, and leakage from perifoveal capillaries in the early frames developing into the classic ‘petalloid’ pattern in late frames. Optic nerve staining may also be seen and aids to distinguish pseudophakic PCME from other causes of CME.

OCT has become widely adopted and allows convenient monitoring of disease activity. PCME is characterized by loss of the foveal depression, retinal thickening, and cystic hyporeflective lesions. OCT also allows the detection of vitreoretinal traction and lamellar holes. However, despite OCT's superior sensitivity and convenience, fluorescein angiography remains the gold standard because it can rule out other causes of CME.

The differential diagnosis of PCME is broad and includes macular edema due to diabetes, RVO, uveitis, radiation retinopathy, hypertensive retinopathy, retinal degenerations, and choroidal tumors. Preoperative screening of such patients for macular edema may be warranted, because subclinical macular edema may worsen after cataract extraction and can negatively affect postoperative outcomes. Additionally, as the patients undergoing cataract surgery comprise an age group in which there is a high prevalence of age-related macular degeneration (AMD), care should be taken not to misdiagnose neovascular AMD as PCME.

Back to Top | Article Outline

TREATMENT

There is currently no standardized treatment or prophylactic protocol for PCME, because well designed large RCTs with long-term follow-up are lacking (Table 1) [2▪▪]. Topical NSAIDs and topical corticosteroids are nevertheless first-line modalities.

Table 1

Table 1

Back to Top | Article Outline

NSAIDs

Topical NSAIDs have become the mainstay of perioperative PCME prophylaxis. Ketorolac 0.4% (Acular; Allergan, Irvine, California, USA), diclofenac 0.1% (Voltaren; Bausch & Lomb, Tampa, Florida, USA), bromfenac 0.09% (Xibrom/Bromday; Ista Pharmaceuticals, Irvine, California, USA), and the relatively new nepafenac 0.1% (Nevanac; Alcon, Fort Worth, Texas, USA) are US Food and Drug Administration (FDA) approved for postoperative inflammation (not for PCME). Nepafenac is a prodrug that is converted into its active product amfenac by intraocular hydrolases. Both bromfenac and nepafenac have been detected in the rabbit retina after topical administration, but it is unclear whether this translates into superior clinical efficacy [21,22].

Recent prophylaxis trials have compared topical corticosteroid monotherapy with combination therapy with NSAIDs. In a masked multicenter RCT, Wittpenn et al.[23] showed that at week 4, clinical/OCT CME developed in five of 278 patients who received perioperative prednisolone, and in none of 268 who also received ketorolac (P = 0.032). Yavas et al.[24] in an unmasked RCT with 189 patients, reported angiographic PCME in 0% who received preoperative and postoperative topical indomethacin, 15% of those who received indomethacin only postoperatively, and 33% of controls (P < 0.001). Another unmasked RCT of 98 patients demonstrated that ketorolac prophylaxis resulted in lower total macular volume compared with controls at 1 month after surgery (P = 0.009), with 46.1% (P = 0.030) macular swelling reduction [25]. A retrospective comparative review of 450 patients found that no patients who received nepafenac prophylaxis developed clinical PCME, compared with five in the control group (P = 0.0354) [26].

Several comparative effectiveness trials between NSAID and corticosteroid prophylaxis have been conducted recently. Results of one double-masked RCT of 50 patients demonstrated that patients in the fluorometholone arm were more likely to develop angiographic PCME compared with the diclofenac arm (P = 0.08 at 2 weeks, P = 0.001 at 5 weeks) [27]. Asano et al.[28] also reported that the incidence of angiographic PCME 5 weeks postoperatively was 18.8% in those treated with diclofenac, compared with 58.0% of the betamethasone group (P < 0.001) in a double-masked multicenter RCT involving 142 patients. Another open-label trial with 62 diabetic patients suggested that prophylaxis with bromfenac was superior to betamethasone and fluorometholone [29▪].

Based on such data, off-label PCME prophylaxis has become widely adopted [2▪▪,30▪▪]. However, the longest follow-up in the aforementioned studies is 3 months, and no study has provided follow-up beyond 1 year [30▪▪]. It is therefore uncertain whether PCME prophylaxis prevents chronic/late onset PCME, and if there are long-term visual benefits. Nevertheless, eyes at high risk for complications, such as those with histories of uveitis, DME, or surgical complications, may benefit from prophylaxis [4,15].

There is very little evidence regarding optimal treatment of acute PCME. A small RCT in 2000 reported by Heier et al. [31] compared the efficacies of topical ketorolac, prednisolone, and the combination of the two in 28 patients who developed PCME within 21–90 days after cataract surgery. The combination therapy resulted in superior visual acuity outcomes compared with monotherapy of either agent alone.

Studies have investigated NSAIDs as treatment for chronic PCME, but there are no recent RCTs. Flach et al.[32] reported in 1991 a multicenter RCT involving 120 patients with chronic aphakic or CME which revealed that patients treated with ketorolac achieved better visual acuity than placebo after 30 (P = 0.04), 60 (P = 0.02), and 90 days (P = 0.01). A recent series of 11 patients with chronic PCME who did not tolerate topical steroids showed that nepafenac improved visual acuity (P < 0.0001) and decreased retinal thickness (P < 0.0001) [33].

Intravitreal treatments are now frequently used for various vitreoretinal disorders, but intravitreal NSAIDs have not been investigated until recently. Soheilian et al.[34▪] reported the first study of intravitreal diclofenac 500 μg/0.1 ml to treat macular edema of various causes in 10 eyes and showed that visual acuity improved in seven eyes at 8 weeks (P = 0.019), including one eye with PCME, but there were no significant improvements in central macular thickness (CMT). No toxic effects were noted; further studies may be warranted.

Back to Top | Article Outline

Corticosteroids

Topical corticosteroids are commonly used in prophylaxis and treatment of PCME, but the evidence is surprisingly limited. The true efficacy of steroids appears to be confounded by concomitant use of NSAIDs in most studies [2▪▪], although NSAIDs and corticosteroids may work synergistically, at least in the short-term [1].

Sub-Tenon's and retrobulbar corticosteroids have been shown to be effective for PCME refractory to topical treatments (Fig. 1) [7▪]. However, studies in DME have indicated that intravitreal corticosteroids may be more efficacious than periocular modalities [35]. Intravitreal triamcinolone has been well studied in DME and RVO, but data supporting its use in PCME are still limited [9▪]. In an RCT of 41 eyes with moderate nonproliferative diabetic retinopathy, Ahmadabadi et al.[36▪] showed that clinical macular edema developed in four eyes after routine phacoemulsification, compared with no case in eyes that received intraoperative intravitreal triamcinolone (P = 0.059). Visual acuity was better in the treatment group at 1 month (P = 0.045), but not sustained at 6 months. The disadvantages of intravitreal delivery include the risk of endophthalmitis and the need for multiple injections.

FIGURE 1

FIGURE 1

Sustained drug delivery systems (DDSs) have been developed to reduce the frequency of treatments. Ozurdex (Allergan) is an injectable, biodegradable intravitreal dexamethasone implant [37]. It is has been approved by FDA for macular edema secondary to RVO and noninfectious posterior uveitis [38]. A phase II trial subgroup analysis showed that eight of 27 (30%) patients with refractory CME showed at least a 10-letter improvement [39]. Another phase II study is currently enrolling patients to investigate Ozurdex in treating combined CME and DME after cataract surgery [40].

Other intravitreal corticosteroid implants that may eventually have a role in treatment of CME include Retisert (Bausch & Lomb, Rochester, New York, USA), a surgically implanted fluocinolone implant that has been approved by FDA for noninfectious posterior uveitis, with encouraging data from phase III DME studies [41], Iluvien (Alimera Sciences, Alpharetta, Georgia, USA), an injectable fluocinolone implant with preliminary data for DME [42], IBI-20089, a sustained release preparation of triamcinolone acetonide (Icon Bioscience, Sunnyvale, California, USA), with phase I data for CME secondary to RVO [43].

Back to Top | Article Outline

Anti-vascular endothelial growth factor treatments

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis and has been targeted successfully in neovascular diseases, but it is also implicated in the inflammation and capillary permeability that causes CME. Bevacizumab (Avastin, Genentech, South San Francisco, California, USA) is a full-length humanized monoclonal antibody that inhibits VEGF-A. Arevalo et al.[44] reported on a series of 28 eyes with chronic PCME treated with intravitreal bevacizumab as a monotherapy. Mean visual acuity improved from 20/160 to 20/63 (P < 0.0001) and mean CMT decreased (P < 0.0001), but eight patients required a second injection and four patients a third.

The treatment of refractory PCME is a challenge. One group reported that intravitreal bevacizumab did not improve visual acuity in 16 eyes with PCME refractory to various treatments [45]. However, a subsequently published series of 36 eyes with chronic PCME refractory to previous topical, periocular, systemic, and intravitreal treatments reported that an average of 2.7 bevacizumab injections resulted in improved visual acuity (P < 0.0001) and CMT (P < 0.0001) at 12 months [46]. Another group also reported promising visual and anatomic outcomes in a series of 10 patients with refractory PCME [47]. Triple therapy with intravitreal triamcinolone, intravitreal bevacizumab, and topical NSAIDs has been shown to be effective as well [48▪]. The above studies are encouraging, but all are uncontrolled.

Back to Top | Article Outline

Vitrectomy

Pars plana vitrectomy is considered when PCME is complicated by vitreoretinal traction, and/or if the PCME is unresponsive to medical treatment for more than 1 year and less than 2 years [7▪]. Even in the absence of vitreous traction, vitrectomy may reduce the concentration of inflammatory mediators and growth factors. In a 1985 RCT of 68 eyes with chronic aphakic CME, Fung [49] found that vitrectomized eyes had better visual outcomes compared with controls (P < 0.01). However, the use of corticosteroids in the treatment group may have confounded the results, which may not necessarily apply to PCME. Preliminary data from a RCT that enrolled 41 eyes with chronic PCME, randomized to posterior hyaloid removal or internal limiting membrane (ILM) peeling, found that there was no added benefit in performing ILM peeling [50]. Further studies are clearly needed to better define the role of vitrectomy in PCME.

Back to Top | Article Outline

Other treatments

Oral carbonic anhydrase inhibitors (CAIs) may be considered in refractory PCME. Encouraging results have been reported in small series and case reports, but their use is often limited by a severe side-effect profile [9▪]. Topical CAIs have not yet been investigated in PCME.

Recent small pilot studies have also examined subcutaneous interferon alpha (IFN-a; Imgenex, San Diego, California, USA) [51] and intravitreal infliximab (Remicade, Centocor Ortho Biotech, Horsham, Pennsylvania, USA) with mixed results [52,53].

Back to Top | Article Outline

CONCLUSION

There remains a lack of well designed RCTs to evaluate the medical and surgical treatment of PCME. We would benefit from the following: a better understanding of disease pathogenesis to offer more targeted approaches, reports on long-term outcomes of PCME prophylaxis, comparative effectiveness studies between the different NSAIDs, standardization of the definition of PCME across future studies, and larger studies to investigate intravitreal treatments for refractory PCME. As the volume of cataract surgeries will continue to increase to accommodate the aging population, a better understanding of PCME will be essential.

Back to Top | Article Outline

Acknowledgements

None.

Back to Top | Article Outline

Conflicts of interest

I.K.K. has received research support from Genentech, Inc. and has served as a consultant for Genentech and Novartis.

The authors do not report any conflicts of interest.

Back to Top | Article Outline

REFERENCES AND RECOMMENDED READING

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest

Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 75).

Back to Top | Article Outline

References

1. Flach AJ. The incidence, pathogenesis and treatment of cystoid macular edema following cataract surgery. Trans Am Ophthalmol Soc 1998; 96:557–634.
Shelsta HN, Jampol LM. Pharmacologic therapy of pseudophakic cystoid macular edema: 2010 update. Retina 2011; 31:4–12.

This review discusses the evolution (or lack of) of PCME treatment since the 1980s.

3. Kim SJ, Belair ML, Bressler NM, et al. A method of reporting macular edema after cataract surgery using optical coherence tomography. Retina 2008; 28:870–876.
4. Belair ML, Kim SJ, Thorne JE, et al. Incidence of cystoid macular edema after cataract surgery in patients with and without uveitis using optical coherence tomography. Am J Ophthalmol 2009; 148:128–135.
5. Perente I, Utine CA, Ozturker C, et al. Evaluation of macular changes after uncomplicated phacoemulsification surgery by optical coherence tomography. Curr Eye Res 2007; 32:241–247.
6. Henderson BA, Kim JY, Ament CS, et al. Clinical pseudophakic cystoid macular edema. Risk factors for development and duration after treatment. J Cataract Refract Surg 2007; 33:1550–1558.
Loewenstein A, Zur D. Postsurgical cystoid macular edema. Dev Ophthalmol 2010; 47:148–159.

This paper is a comprehensive review of PCME.

8. Schmier JK, Halpern MT, Covert DW, Matthews GP. Evaluation of costs for cystoid macular edema among patients after cataract surgery. Retina 2007; 27:621–628.
Benitah NR, Arroyo JG. Pseudophakic cystoid macular edema. Int Ophthalmol Clin 2010; 50:139–153.

This review provides detailed discussions of various PCME studies.

10. Cohen SM, Davis A, Cukrowski C. Cystoid macular edema after pars plana vitrectomy for retained lens fragments. J Cataract Refract Surg 2006; 32:1521–1526.
11. Hayashi K, Igarashi C, Hirata A, Hayashi H. Changes in diabetic macular oedema after phacoemulsification surgery. Eye (Lond) 2009; 23:389–396.
12. Rashid S, Young LH. Progression of diabetic retinopathy and maculopathy after phacoemulsification surgery. Int Ophthalmol Clin 2010; 50:155–166.
13. Shah AS, Chen SH. Cataract surgery and diabetes. Curr Opin Ophthalmol 2010; 21:4–9.
14. Jiramongkolchai K, Lalezary M, Kim SJ. Influence of previous vitrectomy on incidence of macular oedema after cataract surgery in diabetic eyes. Br J Ophthalmol 2011; 95:524–529.
15. Horozoglu F, Yanyali A, Aytug B, et al. Macular thickness changes after phacoemulsification in previously vitrectomized eyes for diabetic macular edema. Retina 2011; 31:1095–1100.
16. Ram J, Gupta A, Kumar S, et al. Phacoemulsification with intraocular lens implantation in patients with uveitis. J Cataract Refract Surg 2010; 36:1283–1288.
17. Miyake K, Ibaraki N, Goto Y, et al. ESCRS Binkhorst lecture 2002: pseudophakic preservative maculopathy. J Cataract Refract Surg 2003; 29:1800–1810.
18. Arcieri ES, Santana A, Rocha FN, et al. Blood-aqueous barrier changes after the use of prostaglandin analogues in patients with pseudophakia and aphakia: a 6-month randomized trial. Arch Ophthalmol 2005; 123:186–192.
19. Panteleontidis V, Detorakis ET, Pallikaris IG, Tsilimbaris MK. Latanoprost-dependent cystoid macular edema following uncomplicated cataract surgery in pseudoexfoliative eyes. Ophthalmic Surg Lasers Imaging 2010; 41:1–5.
20. Law SK, Kim E, Yu F, Caprioli J. Clinical cystoid macular edema after cataract surgery in glaucoma patients. J Glaucoma 2010; 19:100–104.
21. Gamache DA, Graff G, Brady MT, et al. Nepafenac, a unique nonsteroidal prodrug with potential utility in the treatment of trauma-induced ocular inflammation. I: Assessment of anti-inflammatory efficacy. Inflammation 2000; 24:357–370.
22. Baklayan GA, Patterson HM, Song CK, et al. 24-h evaluation of the ocular distribution of (14)C-labeled bromfenac following topical instillation into the eyes of New Zealand White rabbits. J Ocul Pharmacol Ther 2008; 24:392–398.
23. Wittpenn JR, Silverstein S, Heier J, et al. A randomized, masked comparison of topical ketorolac 0.4% plus steroid vs steroid alone in low-risk cataract surgery patients. Am J Ophthalmol 2008; 146:554–560.
24. Yavas GF, Ozturk F, Kusbeci T. Preoperative topical indomethacin to prevent pseudophakic cystoid macular edema. J Cataract Refract Surg 2007; 33:804–807.
25. Almeida DR, Johnson D, Hollands H, et al. Effect of prophylactic nonsteroidal antiinflammatory drugs on cystoid macular edema assessed using optical coherence tomography quantification of total macular volume after cataract surgery. J Cataract Refract Surg 2008; 34:64–69.
26. Wolf EJ, Braunstein A, Shih C, Braunstein RE. Incidence of visually significant pseudophakic macular edema after uneventful phacoemulsification in patients treated with nepafenac. J Cataract Refract Surg 2007; 33:1546–1549.
27. Miyake K, Nishimura K, Harino S, et al. The effect of topical diclofenac on choroidal blood flow in early postoperative pseudoaphakias with regard to cystoid macular edema formation. Invest Ophthalmol Vis Sci 2007; 48:5647–5652.
28. Asano S, Miyake K, Ota I, et al. Reducing angiographic cystoid macular edema and blood-aqueous barrier disruption after small-incision phacoemulsification and foldable intraocular lens implantation: multicenter prospective randomized comparison of topical diclofenac 0.1% and betamethasone 0.1%. J Cataract Refract Surg 2008; 34:57–63.
Endo N, Kato S, Haruyama K, et al. Efficacy of bromfenac sodium ophthalmic solution in preventing cystoid macular oedema after cataract surgery in patients with diabetes. Acta Ophthalmol 2010; 88:896–900.

This is the first prospective head-to-head comparative effectiveness study comparing topical bromfenac to topical corticosteroids in PCME prophylaxis.

Kim SJ, Flach AJ, Jampol LM. Nonsteroidal anti-inflammatory drugs in ophthalmology. Surv Ophthalmol 2010; 55:108–133.

At the time of writing, this is the most recent major review of ophthalmic NSAID use.

31. Heier JS, Topping TM, Baumann W, et al. Ketorolac versus prednisolone versus combination therapy in the treatment of acute pseudophakic cystoid macular edema. Ophthalmology 2000; 107:2034–2038.discussion 2039.
32. Flach AJ, Jampol LM, Weinberg D, et al. Improvement in visual acuity in chronic aphakic and pseudophakic cystoid macular edema after treatment with topical 0.5% ketorolac tromethamine. Am J Ophthalmol 1991; 112:514–519.
33. Warren KA, Fox JE. Topical nepafenac as an alternate treatment for cystoid macular edema in steroid responsive patients. Retina 2008; 28:1427–1434.
Soheilian M, Karimi S, Ramezani A, Peyman GA. Pilot study of intravitreal injection of diclofenac for treatment of macular edema of various etiologies. Retina 2010; 30:509–515.

This paper describes the first study to examine an intravitreal NSAID in human eyes.

35. Takata C, Messias A, Folgosa MS, et al. Intravitreal injection versus subtenon infusion of triamcinolone acetonide during cataract surgery in patients with refractory diabetic macular edema. Retina 2010; 30:562–569.
Ahmadabadi HF, Mohammadi M, Beheshtnejad H, Mirshahi A. Effect of intravitreal triamcinolone acetonide injection on central macular thickness in diabetic patients having phacoemulsification. J Cataract Refract Surg 2010; 36:917–922.

This is the first RCT evaluating intravitreal triamcinolone for PCME.

37. London NJ, Chiang A, Haller JA. The dexamethasone drug delivery system: indications and evidence. Adv Ther 2011; 28:351–366.
38. United States Food and Drug Administration. Label and approval history. http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/index.cfm. [Accessed 6 June 2010]
39. Williams GA, Haller JA, Kuppermann BD, et al. Dexamethasone posterior-segment drug delivery system in the treatment of macular edema resulting from uveitis or Irvine-Gass syndrome. Am J Ophthalmol 2009; 147:1048–1054.
40. United States National Institutes of Health. Ozurdex for combined pseudophakic cystoid macular edema and diabetic macular edema after cataract surgery. http://clinicaltrials.gov/ct2/show/NCT01284478. [Accessed 5 June 2011]
41. Campochiaro PA, Brown DM, Pearson A, et al. Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology 2011; 118:626–635.
42. Antoszyk AN. Efficacy and safety of Iluvien (fluocinolone acetonide [FAc] intravitreal insert) for the treatment of diabetic macular edema. Invest Ophthalmol Vis Sci 2011; 52:E-Abstract 6645.
43. Lim JI, Fung AE, Wieland M, et al. Sustained-release intravitreal liquid drug delivery using triamcinolone acetonide for cystoid macular edema in retinal vein occlusion. Ophthalmology 2011; 118:1416–1422.
44. Arevalo JF, Garcia-Amaris RA, Roca JA, et al. Primary intravitreal bevacizumab for the management of pseudophakic cystoid macular edema: pilot study of the Pan-American Collaborative Retina Study Group. J Cataract Refract Surg 2007; 33:2098–2105.
45. Spitzer MS, Ziemssen F, Yoeruek E, et al. Efficacy of intravitreal bevacizumab in treating postoperative pseudophakic cystoid macular edema. J Cataract Refract Surg 2008; 34:70–75.
46. Arevalo JF, Maia M, Garcia-Amaris RA, et al. Intravitreal bevacizumab for refractory pseudophakic cystoid macular edema: the Pan-American Collaborative Retina Study Group results. Ophthalmology 2009; 116:1481–1487.
47. 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.
Warren KA, Bahrani H, Fox JE. NSAIDs in combination therapy for the treatment of chronic pseudophakic cystoid macular edema. Retina 2010; 30:260–266.

This paper describes the first study to examine triple therapy with intravitreal triamcinolone, intravitreal bevacizumab, and a topical NSAID.

49. Fung WE. Vitrectomy for chronic aphakic cystoid macular edema. Results of a national, collaborative, prospective, randomized investigation. Ophthalmology 1985; 92:1102–1111.
50. Agarwal A, Lamba M. The role of internal limiting membrane peeling in the surgical management of chronic pseudophakic cystoid macular edema [abstract]. In: American Academy of Ophthalmology Annual Meeting; 16–19 October 2010; Chicago, IL; poster 247.
51. Deuter CM, Gelisken F, Stubiger N, et al. Successful treatment of chronic pseudophakic macular edema (Irvine-Gass syndrome) with interferon alpha: a report of three cases. Ocul Immunol Inflamm 2011; 19:216–218.
52. Arevalo JF, Wu L, Hernandez-Bogantes E. Intravitreal TNF inhibitors in the treatment of refractory pseudophakic cystoid macular edema: a pilot study from the pan american collaborative retina study group [abstract]. In: American Academy of Ophthalmology Annual Meeting; 16–19 October; Chicago, IL; poster 247.
53. Giganti M, Beer PM, Lemanski N, et al. Adverse events after intravitreal infliximab (Remicade). Retina 2010; 30:71–80.
Keywords:

anti-vascular endothelial growth factor; corticosteroids; Irvine–Gass syndrome; nonsteroidal anti-inflammatory drugs; pseudophakic cystoid macular edema

© 2012 Lippincott Williams & Wilkins, Inc.