CME after cataract surgery

The latest on what surgeons can do to crush cystoid macular edema.

Cystoid macular edema (CME) remains one of the most important causes of postoperative vision loss after cataract surgery1 and can result in visual impairment in up to 14% of eyes.2 Annual total ophthalmic claims can go up to 41% higher in Medicare patients with CME.3 This article offers a review of the latest evidence on preventing and treating it.


What it is

First described in 1953 by S. Rodman Irvine, MD, and J. Donald M. Gass, MD,4 CME is precipitated by the release of prostaglandins and other inflammatory mediators after cataract surgery, resulting in an increase in perifoveal capillary permeability, blood-retinal barrier disruption and subsequent fluid accumulation and cystoid changes in the retina.5 CME begins with inner nuclear layer (INL) cystic changes and progresses to involve combined INL and outer plexiform layer (OPL) with subsequent subretinal fluid accumulation.

The INL is the most frequently involved layer, and isolated INL cystoid changes can be present within the first 3 postoperative months with no visual significance,6 even in the fellow, phakic eye.7,8

CME has been classified as clinical (observed in slit lamp examination in patients with measurable decline in distance corrected visual acuity), angiographic (leakage detected on fluorescein angiography) and as presence of intraretinal fluid with or without subretinal fluid on OCT.9

CME risk and rates

Due to the diverse classification and the different studied patient populations with different risk factors, the reported CME incidence rate varies substantially between studies.1,3,9-18 After modern small-incision cataract surgery in healthy individuals, CME has been reported as high as 19% using fluorescein angiography criteria, but as low as 0.82% using visual acuity and OCT findings.1,9,10 Comparatively, certain groups are at higher risk of developing CME (Table), particularly uveitis patients,1,11 diabetic patients with or without retinopathy,3,12 eyes with capsule rupture during surgery with or without vitreous loss, patients with pseudoexfoliation,13 who frequently require pupillary expansion devices intraoperatively,14 patients with pre-existing epiretinal membrane,15 history of retinal vein occlusion, especially those who experienced macular edema after occlusion16 and retinal detachment repair.1

Table: High-risk CME groups11,12,14-19
Uveitis 2.8
Diabetes with retinopathy 6.2
Diabetes without retinopathy 1.8
Posterior capsule rupture 2.6
Use of pupillary expansion device 5.4
Pre-existing epiretinal membrane 5.6
History of vein occlusion 4.4
History of RD repair 3.9

Interestingly, postoperative use of topical prostaglandin analogues and beta blockers for management of glaucoma has also been associated with an increased risk of CME. Therefore, IOP management with these agents should be pondered with this increased risk.

Considering that the etiology of CME stems from increased levels of intraocular prostaglandins, it may be assumed that femtosecond laser-assisted cataract surgery, known to increase the level of prostaglandins in the anterior chamber,20 poses a higher risk for postoperative CME. The literature in this regard is still inconclusive, with conflicting results in various peer-reviewed publications. Some studies show a decrease in the rate of postoperative CME,21 while others show no significant difference between FLACS and manual cataract surgery22 or an increased risk for CME when femtosecond laser is part of the surgical procedure.23,24

Nevertheless, it is worth considering this potential outcome, especially in patients at higher-risk for CME.


Less CME, but increasingly crucial to treat

CME after uncomplicated cataract surgery in low-risk patients tends to resolve spontaneously,5,25,26 and no evidence suggests that perioperative anti-inflammatory treatment affects incidence or long-term visual outcomes. Additionally, advances in cataract surgery, such as more efficient phacodynamics and reduced time of surgery, and the insertion of a posterior chamber IOL have dramatically reduced the risk of postoperative CME.

However, perioperative control of inflammation may hasten the speed of visual recovery in the first several weeks postoperatively, and this becomes relevant in the days of refractive cataract surgery. Since the early stages of cataract surgery, the mainstay of perioperative anti-inflammatory treatment has been topical steroids, with no difference in the preventive efficacy of prednisolone vs. dexamethasone.27

The role of NSAIDs

In the 1980s, NSAIDs began to be considered as an adjuvant — or even replacement — of postoperative treatment with topical steroids for routine cataract surgical cases. Initial studies evaluated indomethacin or ketorolac in addition to corticosteroid treatment25,26,28 and showed a significant reduction of angiographic leakage in the initial postoperative period (as early as 10 weeks),26 but no significant difference in angiographic findings or visual acuity beyond 3 months.

Later publications also showed less postoperative angiographic CME in eyes treated with diclofenac (18.8%) vs. eyes treated with betamethasone (58%) at 5 weeks but no significant differences in visual acuity between groups at 8 weeks.29 Even studies comparing 1 to 3 days preoperative treatment with ketorolac to only postoperative treatment have shown significantly better visual outcomes at 2 weeks compared with control eyes, but this difference did not persist by 3 months.30

There is a lack of level I evidence supporting long-term benefits of NSAID therapy in preventing vision loss attributed to CME.31 This is likely due to the selective blockage of cyclooxygenase enzyme by NSAIDS, which inhibits the synthesis of pro-inflammatory prostaglandins,5,32 compared to the inhibition of prostaglandins and leukotrienes by corticosteroids. Corticosteroids also downregulate other inflammation-mediated processes, providing broader anti-inflammatory properties compared to NSAIDs.

It therefore remains to be determined if a synergistic effect occurs when both anti-inflammatory drugs are combined, or if dual treatment is simply redundant.

Hence, topical NSAIDs, though approved by the FDA for “treatment of pain and inflammation associated with cataract surgery,” are yet to be approved for the prevention or treatment of CME or for treatment durations longer than 14 days.31 NSAIDs are currently used off-label by many ophthalmic surgeons in the United States as prophylaxis and treatment of CME, especially in high-risk patients.

More recently, newer NSAID formulations with better intraocular penetrations, such as bromfenac and nepafenac, have been compared to topical steroids alone and to other NSAIDs.33-35 Nepafenac has been equivalent to diclofenac33 and ketorolac34 with no significant differences in final visual acuity at 4 weeks. Bromfenac 0.09% alone has shown CME development in as low as 0.44% of cases, compared to the combination of prednisolone 1% and generic (2.2%) or name-brand ketorolac 0.45% (0.9%),10 as well as to dexamethasone alone.35

The potential prophylactic benefit of perioperative treatment with topical NSAIDs appears to exist in high-risk patients. Patients with pseudoexfoliation syndrome19 and diabetes,36 who are treated with topical bromfenac 0.09% or nepafenac 1% combined with a topical steroid, experience lower rates of postoperative CME. Preoperative treatment in diabetic patients, however, may not offer added benefits compared to postoperative treatment only.37

Steroids and delivery methods

Newer approaches for perioperative prophylaxis of intraocular inflammation include:

  • Preoperative oral corticosteroids in high-risk patients11
  • Intracameral dexamethasone drug deposits38-41
  • Intracameral administration of triamcinolone acetonide42,43
  • Transzonular intravitreal administration of compound antibiotic and anti-inflammatory drugs (caution is advised given the risk of iatrogenic zonular instability)
  • Fluocinolone acetonide intravitreal implant44
  • Perioperative subconjunctival triamcinolone.45,46

Interestingly, none of these steroid delivery methods have yet been found to increase the risk of postoperative IOP spike compared to topical steroids.40,47,48 New drug delivery methods are also being studied, such as intracanalicular dexamethasone deposits49 and using the IOL as a drug delivery device.50-52


Our options

Though no strong evidence from randomized controlled trials shows superior outcomes compared to observation in uncomplicated eyes, the combination of topical NSAID and topical steroid for at least 6 weeks has been the main off-label approach for treatment of visually significant CME. However, other treatment modalities have been proposed and shown results that are promising but still comparable to topical treatments in the majority of cases: intravitreal dexamethasone implants,53 especially in diabetic patients54 and patients with vitrectomized eyes,55 intravitreal anti-VEGF drugs,56,57 sub-tenon’s corticosteroids58 and oral acetazolamide,59 which shows beneficial in patients with known steroid-induced elevation in IOP.

Because CME is also known to resolve spontaneously, we need further large population randomized controlled studies with longer follow up to assess the true benefit of all these therapeutic approaches.


CME arises from changes in the INL and OPL of the retina resulting from the increase in the level of intraocular inflammation after even uncomplicated cataract surgery. In certain groups, the incidence is much higher and can lead to significant vision loss. We have limited evidence on best strategies for prophylaxis, but the most effective approach to date appears to be treating prophylactically only those at higher risk for developing CME after cataract surgery.

There is a weak association between angiographic and OCT evidence of CME and visual acuity and strong evidence suggesting that CME after cataract surgery in low-risk patients resolves spontaneously. Therefore, subclinical CME diagnosed by OCT or angiography in low-risk cases may be observed and only treated should it become visually significant.

Conversely, in high-risk patients (who are more prone to recalcitrant edema and decline in vision), medical treatment can be initially considered followed by intravitreal anti-inflammatory, or anti-VEGF injections if there is no response. OM


  1. Chu CJ, Johnston RL, Buscombe C, et al. Risk factors and incidence of macular edema after cataract surgery: A database study of 81984 eyes. Ophthalmology. 2016;123:316-323.
  2. 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.
  3. 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.
  4. Irvine SR. A newly defined vitreous syndrome following cataract surgery. Am J Ophthalmol. 1953;36:599-619.
  5. Miyake K, Ibaraki N. Prostaglandins and cystoid macular edema. Surv Ophthalmol. 2002;47 Suppl 1:S203-218.
  6. Sigler EJ, Randolph JC, Kiernan DF. Longitudinal analysis of the structural pattern of pseudophakic cystoid macular edema using multimodal imaging. Graefes Arch Clin Exp Ophthalmol. 2016;254:43-51.
  7. Pannullo NA, Chu RL, Sigler EJ. Inner nuclear layer cystic changes in phakic fellow eyes of patients with acute pseudophakic cystoid macular edema. Ophthalmic Surg Lasers Imaging Retina. 2019;50:522-524.
  8. Yonekawa Y, Kim IK. Pseudophakic cystoid macular edema. Curr Opin Ophthalmol. 2012;23:26-32.
  9. Kim SJ, Bressler NM. Optical coherence tomography and cataract surgery. Curr Opin Ophthalmol. 2009;20:46-51.
  10. Walter KA, Lee RY, Chen K, Komanski C. Incidence of cystoid macular edema following routine cataract surgery using NSAIDs alone or with corticosteroids. Arq Bras Oftalmol. 2020;83:55-61.
  11. Bélair 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 e2.
  12. Kim SJ, Equi R, Bressler NM. Analysis of macular edema after cataract surgery in patients with diabetes using optical coherence tomography. Ophthalmology. 2007;114:881-889.
  13. Ilveskoski L, Taipale C, Holmström EJ, Tuuminen R. Macular edema after cataract surgery in eyes with and without pseudoexfoliation syndrome. Eur J Ophthalmol. 2019;29:504-509.
  14. Taipale C, Holmström EJ, Ilveskoski L, Tuuminen R. Incidence of pseudophakic cystoid macular edema in eyes with and without pupil expansion device. Acta Ophthalmol. 2019;97:688-694.
  15. Schaub F, Adler W, Enders P, et al. Preexisting epiretinal membrane is associated with pseudophakic cystoid macular edema. Graefes Arch Clin Exp Ophthalmol. 2018;256:909-917.
  16. Cho HJ, Hwang HJ, Kim HS, et al. Macular edema after cataract surgery in eyes with preoperative retinal vein occlusion. Retina. 2018;38:1180-1186.
  17. Wendel C, Zakrzewski H, Carleton B, Etminan M, Mikelberg FS. Association of postoperative topical prostaglandin analog or beta-blocker use and incidence of pseudophakic cystoid macular edema. J Glaucoma. 2018;27:402-406.
  18. Walkden A, Porter LF, Morarji J, Kelly SP, Sioras E. Pseudophakic cystoid macular edema and spectral-domain optical coherence tomography-detectable central macular thickness changes with perioperative prostaglandin analogs. J Cataract Refract Surg. 2017;43:1027-1030.
  19. Ilveskoski L, Taipale C, Tuuminen R. Anti-inflammatory medication of cataract surgery in pseudoexfoliation syndrome – NSAID is needed. Curr Eye Res. 2019. DOI: 10.1080/02713683.2019.1701686.
  20. Schultz T, Joachim SC, Stellbogen M, Dick HB. Prostaglandin release during femtosecond laser-assisted cataract surgery: main inducer. J Refract Surg. 2015;31:78-81.
  21. Nithianandan H, Jegatheeswaran V, Dalal V, et al. Refractive laser-assisted cataract surgery versus conventional manual surgery: Comparing efficacy and safety in 3144 eyes. Am J Ophthalmol. 2019;206:32-39.
  22. Conrad-Hengerer I, Hengerer FH, Al Juburi M, Schultz T, Dick HB. Femtosecond laser-induced macular changes and anterior segment inflammation in cataract surgery. J Refract Surg. 2014;30:222-226.
  23. Wang J, Su F, Wang Y, Chen Y, Chen Q, Li F. Intra and post-operative complications observed with femtosecond laser-assisted cataract surgery versus conventional phacoemulsification surgery: a systematic review and meta-analysis. BMC Ophthalmol. 2019;19:177.
  24. Ewe SY, Oakley CL, Abell RG, Allen PL, Vote BJ. Cystoid macular edema after femtosecond laser-assisted versus phacoemulsification cataract surgery. J Cataract Refract Surg. 2015;41:2373-2378.
  25. Flach AJ, Stegman RC, Graham J, Kruger LP. Prophylaxis of aphakic cystoid macular edema without corticosteroids. A paired-comparison, placebo-controlled double-masked study. Ophthalmology. 1990;97:1253-1258.
  26. Yannuzzi LA, Landau AN, Turtz AI. Incidence of aphakic cystoid macular edema with the use of topical indomethacin. Ophthalmology. 1981;88:947-954.
  27. Baartman BJ, Gans R, Goshe J. Prednisolone versus dexamethasone for prevention of pseudophakic cystoid macular edema. Can J Ophthalmol. 2018;53:131-134.
  28. Miyake K, Sakamura S, Miura H. Long-term follow-up study on prevention of aphakic cystoid macular oedema by topical indomethacin. Br J Ophthalmol. 1980;64:324-328.
  29. 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.
  30. Donnenfeld ED, Perry HD, Wittpenn JR, et al. Preoperative ketorolac tromethamine 0.4% in phacoemulsification outcomes: pharmacokinetic-response curve. J Cataract Refract Surg. 2006;32:1474-1482.
  31. Kim SJ, Schoenberger SD, Thorne JE, et al. Topical nonsteroidal anti-inflammatory drugs and cataract surgery: A report by the American Academy of Ophthalmology. Ophthalmology. 2015;122:2159-2168.
  32. Flach AJ. Topical nonsteroidal antiinflammatory drugs in ophthalmology. Int Ophthalmol Clin. 2002;42:1-11.
  33. Ylinen P, Taipale C, Lindholm JM, et al. Postoperative management in cataract surgery: nepafenac and preservative-free diclofenac compared. Acta Ophthalmol. 2018;96:853-859.
  34. Almeida DR, Khan Z, Xing L, et al. Prophylactic nepafenac and ketorolac versus placebo in preventing postoperative macular edema after uneventful phacoemulsification. J Cataract Refract Surg. 2012;38:1537-1543.
  35. Coassin M, De Maria M, Mastrofilippo V, et al. Anterior chamber inflammation after cataract surgery: A randomized clinical trial comparing bromfenac 0.09% to dexamethasone 0.1. Adv Ther. 2019;36:2712-2722.
  36. McCafferty S, Harris A, Kew C, et al. Pseudophakic cystoid macular edema prevention and risk factors; prospective study with adjunctive once daily topical nepafenac 0.3% versus placebo. BMC Ophthalmol. 2017;17:16.
  37. Danni R, Viljanen A, Aaronson A, Tuuminen R. Preoperative anti-inflammatory treatment of diabetic patients does not improve recovery from cataract surgery when postoperatively treated with a combination of prednisolone acetate and nepafenac. Acta Ophthalmol. 2019;97:589-595.
  38. Grzybowski A, Brockmann T, Kanclerz P, Pleyer U. Dexamethasone intraocular suspension: A long-acting therapeutic for treating inflammation associated with cataract surgery. J Ocul Pharmacol Ther. 2019;35:525-534.
  39. Donnenfeld E, Holland E. Dexamethasone intracameral drug-delivery suspension for inflammation associated with cataract surgery: A randomized, placebo-controlled, Phase III trial. Ophthalmology. 2018;125:799-806.
  40. Donnenfeld ED, Solomon KD, Matossian C. Safety of IBI-10090 for inflammation associated with cataract surgery: Phase 3 multicenter study. J Cataract Refract Surg. 2018;44:1236-1246.
  41. Gupta G, Ram J, Gupta V, et al. Efficacy of intravitreal dexamethasone implant in patients of uveitis undergoing cataract surgery. Ocul Immunol Inflamm. 2019;27:1330-1338.
  42. Wang B, Dong N, Xu B, Liu J, Xiao L. Efficacy and safety of intracameral triamcinolone acetonide to control postoperative inflammation after phacotrabeculectomy. J Cataract Refract Surg. 2013;39:1691-1697.
  43. Karalezli A, Borazan M, Akova YA. Intracameral triamcinolone acetonide to control postoperative inflammation following cataract surgery with phacoemulsification. Acta Ophthalmol. 2008;86:183-187.
  44. Sen HN, Abreu FM, Louis TA, et al. Cataract surgery outcomes in uveitis: The multicenter uveitis steroid treatment trial. Ophthalmology. 2016;123:183-190.
  45. Lindholm JM, Taipale C, Ylinen P, Tuuminen R. Perioperative subconjunctival triamcinolone acetonide injection for prevention of inflammation and macular oedema after cataract surgery. Acta Ophthalmol. 2020;98:36-42.
  46. Wielders LHP, Schouten J, Winkens B, et al. Randomized controlled European multicenter trial on the prevention of cystoid macular edema after cataract surgery in diabetics: ESCRS PREMED Study Report 2. J Cataract Refract Surg. 2018;44:836-847.
  47. Karalezli A, Borazan M, Kucukerdonmez C, Akman A, Akova YA. Effect of intracameral triamcinolone acetonide on postoperative intraocular pressure after cataract surgery. Eye (Lond). 2010;24:619-623.
  48. Shorstein NH, Liu L, Waxman MD, Herrinton LJ. Comparative effectiveness of three prophylactic strategies to prevent clinical macular edema after phacoemulsification surgery. Ophthalmology. 2015;122:2450-2456.
  49. Tyson SL, Bafna S, Gira JP, et al. Multicenter randomized phase 3 study of a sustained-release intracanalicular dexamethasone insert for treatment of ocular inflammation and pain after cataract surgery. J Cataract Refract Surg. 2019;45:204-212.
  50. Filipe HP, Bozukova D, Pimenta A, et al. Moxifloxacin-loaded acrylic intraocular lenses: In vitro and in vivo performance. J Cataract Refract Surg. 2019;45:1808-1817.
  51. Ongkasin K, Masmoudi Y, Wertheimer CM, et al. Supercritical fluid technology for the development of innovative ophthalmic medical devices: Drug loaded intraocular lenses to mitigate posterior capsule opacification. Eur J Pharm Biopharm. 2020;149:248-256.
  52. Pimenta AFR, Serro AP, Colaco R, Chauhan A. Drug delivery to the eye anterior chamber by intraocular lenses: An in vivo concentration estimation model. Eur J Pharm Biopharm. 2018;133:63-69.
  53. Guclu H, Pelitli Gurlu V. Comparison of topical nepafenac 0.1% with intravitreal dexamethasone implant for the treatment of Irvine-Gass syndrome. Int J Ophthalmol. 2019;12:258-267.
  54. Khurana RN, Palmer JD, Porco TC, Wieland MR. Dexamethasone intravitreal implant for pseudophakic cystoid macular edema in patients with diabetes. Ophthalmic Surg Lasers Imaging Retina. 2015;46:56-61.
  55. Özdemir HB, Hasanreisoglu M, Yüksel M, et al. Effectiveness of intravitreal dexamethasone implant treatment for diabetic macular edema in vitrectomized eyes. Turk J Ophthalmol. 2019;49:323-327.
  56. Mitropoulos PG, Chatziralli IP, Peponis VG, Drakos E, Parikakis EA. Intravitreal Ranibizumab for the Treatment of Irvine-Gass Syndrome. Ocul Immunol Inflamm. 2015;23:225-231.
  57. 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.
  58. Erden B, Çakir A, Aslan AC, Bölükbasi S, Elçioglu MN. The efficacy of posterior subtenon triamcinolone acetonide injection in treatment of Irvine-Gass syndrome. Ocul Immunol Inflamm. 2019;27:1235-1241.
  59. Pepple KL, Nguyen MH, Pakzad-Vaezi K, et al. Response of inflammatory cystoid macular edema to treatment using oral acetazolamide. Retina. 2019;39:948-955.

About the Author