ABOUT THE RETINA
COVER FOCUS
PROPHYLACTIC TREATMENTS
AGAINST CME AFTER
CATARACT SURGERY
An ESCRS multicenter study aims to provide evidence for the best approach.
BY RUDY M.M.A. NUIJTS, MD, PhD; ROB W.P. SIMONS, BSc; LAURA H.P. WIELDERS, MD;
FRANK J.H.M. van den BIGGELAAR, PhD; BJORN WINKENS, PhD; AND JAN S.A.G. SCHOUTEN, MD, PhD
Cystoid macular edema (CME) is a common complication
that can affect visual acuity after cataract surgery. Studies
using OCT or fluorescein angiography have found it to
occur in up to 23% of nondiabetic patients after uncom-
plicated cataract surgery. Fortunately, CME does not mani-
fest itself to a clinically significant degree in most of those
patients, and it is usually reversible. Clinically significant
CME occurs in 0% to 6% of nondiabetic patients and is
reported in up to 56% of diabetic patients.1-7
The pathophysiology of CME after cataract surgery is not
well understood, although it is believed to be the result of
an inflammatory process initiated by surgical manipulation.
Subsequently, vasodilatation, increased vascular perme-
ability, and blood-retina barrier disruption occur through
downstream mediators including vascular endothelial
growth factor (VEGF), various cytokines, and prostaglan-
dins (Figure 1). As a result, fluid leaks into the retina and
CME develops.8-10
PREVENTING CME
Various therapies have been investigated to prevent the
development of CME after cataract surgery. Most important
among these are antiinflammatory drugs, such as NSAIDs
and corticosteroids, and drugs that directly target mediators
in the above-mentioned pathophysiologic pathway, such as
the anti-VEGF drugs bevacizumab and ranibizumab.
Postoperative treatment with topical NSAIDs, cortico-
steroids, or a combination, is typically used in patients
undergoing cataract surgery. A recent systematic review
by Kessel et al11 compared the efficacy of topical NSAIDs
versus corticosteroids in nondiabetic patients at 1 month
postoperatively. They found that CME occurred in 25.3% of
patients receiving only a topical corticosteroid and in 3.8%
of patients receiving only a topical NSAID (risk ratio [RR]
5.35). High-potency corticosteroids (eg, betamethasone
and dexamethasone) were more effective than less potent
ones (eg, fluorometholone), but they were nonetheless not
as effective as NSAIDs (RR, 4.77 and 5.84 for high- and low-
potency, respectively). It should be noted that this meta-
analysis included six randomized controlled trials (RCTs)—
four from the same Japanese research group and two from
other Asian groups.
No previous studies have compared the efficacy of topi-
cal NSAIDs to topical corticosteroids in diabetic patients.
One study, however, found that CME occurred 30 days
postoperatively in only 2.4% of diabetic patients treated
with a combination treatment of topical NSAIDs and corti-
costeroids and in 8.7% treated with only a corticosteroid.12
It is currently unknown whether topical corticosteroids
have an additive effect to topical NSAIDs in preventing
CME after cataract surgery in nondiabetic or diabetic
patients. Only one study compared an NSAID with combi-
nation treatment, but no patient in either group developed
CME.13
Due to the limited amount of evidence, it is unknown
which NSAID is most effective in preventing CME after
cataract surgery. Only small studies have compared the use
of different NSAIDs after cataract surgery, and in most of
these studies topical corticosteroids were also used in all
patients.
AT A GLANCE
• Eighteen European study centers are participating in
PREMED, an international multicenter study that
aims to provide conclusive evidence for prevention
of CME after cataract surgery in both diabetic and
nondiabetic patients.
• The primary endpoint is the change in central
subfield mean macular thickness on OCT at 6 weeks
postoperative.
MAY 2015 | CATARACT & REFRACTIVE SURGERY TODAY EUROPE  51
COVER FOCUS
It has been recommended to start prophylactic application of
NSAIDs up to 3 days preoperatively, based on a study by Yavas et
al.14 Their study found that CME occurred in 15% of patients who
started using an NSAID postoperatively, but no CME occurred in
a group of patients who started the NSAID 3 days preoperatively.
Figure 1. Pathogenesis of cystoid macular edema after cataract surgery.
COX: cyclooxygenase; PG: prostaglandin; VEGF: vascular endothelial growth factor
Figure 2. Design of the ESCRS PREMED study.
52  CATARACT & REFRACTIVE SURGERY TODAY EUROPE | MAY 2015
Because diabetic patients have a significantly increased
risk of developing CME after cataract surgery, additional
prophylactic treatments have been studied in this popula-
tion. Typically they involve intravitreal injection of a corti-
costeroid or anti-VEGF drug at the end of cataract surgery.
Ahmadabadi et al compared a combination
of topical and intravitreal corticosteroids
to topical corticosteroids alone and found
that the combination treatment was more
effective in preventing CME at 1 month
postoperatively, albeit the difference was not
statistically significant (incidence: 0% vs 19%,
P=.059).15 Similarly, Udaondo et al compared
a combination of intravitreal anti-VEGF agent
and topical corticosteroid to topical corti-
costeroid alone and found a nonsignificant
effect in favor of the combination treatment,
with incidences of CME of 3.7% and 25.92%
with and without anti-VEGF therapy, respec-
tively.16 The nonsignificant findings in these
studies are likely related to the small number
of patients included.
In diabetic patients with diabetic macular
edema preoperatively, it has been shown that
intravitreal bevacizumab at the end of cataract
surgery led to a significant reduction in retinal
thickness and macular volume increase on
OCT.17-21
ESCRS PREMED STUDY
The literature provides no firm evidence, in
the form of well-designed RCTs, for the most
appropriate prophylactic treatment against
CME after cataract surgery. For this reason,
 COVER FOCUS
23% According to studies using OCT or fluorescein angiography, the percentage of nondiabetic
patients who developed CME after uncomplicated cataract surgery

the European Society of Cataract and Refractive Surgeons 15. 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(6):917-922.
(ESCRS) PREvention of Macular EDema after cataract sur- 16. Udaondo P, Garcia-Pous M, Garcia-Delpech S, et al. Prophylaxis of macular edema with intravitreal ranibizumab in
gery (PREMED) study was initiated. patients with diabetic retinopathy after cataract surgery: a pilot study. J Ophthalmol. 2011;2011:159436.
The ESCRS PREMED study is an initiative of the 17. Takamura Y, Kubo E, Akagi Y. Analysis of the effect of intravitreal bevacizumab injection on diabetic macular edema
after cataract surgery. Ophthalmology. 2009;116(6):1151-1157.
University Eye Clinic Maastricht UMC, in the Netherlands, 18. Chen CH, Liu YC, Wu PC. The combination of intravitreal bevacizumab and phacoemulsification surgery in patients with
under the supervision of Rudy M.M.A. Nuijts, MD, PhD. cataract and coexisting diabetic macular edema. J Ocul Pharmacol Ther. 2009;25(1):83-89.
Eighteen European study centers are participating in this 19. Akinci A, Batman C, Ozkilic E, Altinsoy A. Phacoemulsification with intravitreal bevacizumab injection in diabetic
patients with macular edema and cataract. Retina. 2009;29(10):1432-1435.
international multicenter study that aims to provide con- 20. Lanzagorta-Aresti A, Palacios-Pozo E, Menezo Rozalen JL, Navea-Tejerina A. Prevention of vision loss after cataract
clusive evidence for prevention of CME after cataract sur- surgery in diabetic macular edema with intravitreal bevacizumab: a pilot study. Retina. 2009;29(4):530-535.
gery in both diabetic and nondiabetic patients. 21. Cheema RA, Al-Mubarak MM, Amin YM, Cheema MA. Role of combined cataract surgery and intravitreal bevacizumab
injection in preventing progression of diabetic retinopathy: prospective randomized study. J Cataract Refract Surg.
Nondiabetic patients will be treated postoperatively 2009;35(1):18-25.
with topical bromfenac twice daily, dexamethasone four
times daily, or a combination of both eye drops (Figure 2).
Topical treatment starts 2 days preoperatively, as suggested Rudy M.M.A. Nuijts, MD, PhD
by Yavas et al.14 Diabetic patients—who have a higher risk
n University Eye Clinic Maastricht, Maastricht University Medical
Center, Maastricht, Netherlands
of developing CME after cataract surgery—will receive n Atrium Medical Center Parkstad, Heerlen, Netherlands
both bromfenac and dexamethasone eye drops. Further, n Member, CRST Europe Editorial Board
these patients will be randomized to a control group n rudy.nuijts@mumc.nl
receiving no additional treatments, or to a subconjunctival n Financial disclosure: None

injection of triamcinolone acetonide, an intravitreal injec-

tion of bevacizumab, or both. Jan S.A.G. Schouten, MD, PhD
The primary endpoint is the change in central subfield n University Eye Clinic, Maastricht University Medical Center,
mean macular thickness on OCT at 6 weeks postoperative. Maastricht, Netherlands
n Atrium Medical Center Parkstad, Heerlen, Netherlands
Recruitment for this study started in July 2013, and final n Financial disclosure: None
results are expected in 2016.  n
Rob W.P. Simons, BSc
1. Eriksson U, Alm A, Bjärnhall G, et al. Macular edema and visual outcome following cataract surgery in patients with
diabetic retinopathy and controls. Graefes Arch Clin Exp Ophthalmol. 2011;249(3):349-359.
n University Eye Clinic Maastricht, Maastricht University Medical
2. Katsimpris JM, Petropoulos IK, Zoukas G, et al. Central foveal thickness before and after cataract surgery in normal and in Center, Maastricht, Netherlands
diabetic patients without retinopathy. Klin Monbl Augenheilkd. 2012;229(4):331-337. n rob.simons@mumc.nl
3. Mentes J, Erakgun T, Afrashi F, Kerci G. Incidence of cystoid macular edema after uncomplicated phacoemulsification. n Financial disclosure: None
Ophthalmologica. 2003;217(6):408-412.
4. Rossetti L, Chaudhuri J, Dickersin K. Medical prophylaxis and treatment of cystoid macular edema after cataract surgery.
The results of a meta-analysis. Ophthalmology. 1998;105(3):397-405.
Frank J.H.M. van den Biggelaar, PhD
5. Krepler K, Biowski R, Schrey S, et al. Cataract surgery in patients with diabetic retinopathy: visual outcome, progression of
n University Eye Clinic, Maastricht University Medical Center,
diabetic retinopathy, and incidence of diabetic macular oedema. Graefes Arch Clin Exp Ophthalmol. 2002;240(9):735-738. Maastricht, Netherlands
6. Dowler JG, Sehmi KS, Hykin PG, Hamilton AM. The natural history of macular edema after cataract surgery in diabetes. n Financial disclosure: None
Ophthalmology. 1999;106(4):663-668.
7. Diabetic Retinopathy Clinical Research Network Authors/Writing Committee. Macular edema after cataract surgery in
Laura H.P. Wielders, MD, PhD student
eyes without preoperative central-involved diabetic macular edema. JAMA Ophthalmol. 2013;131(7):870-879.
8. Lobo C. Pseudophakic cystoid macular edema. Ophthalmologica. 2012;227(2):61-67.
n University Eye Clinic, Maastricht University Medical Center,
9. Colin J. The role of NSAIDs in the management of postoperative ophthalmic inflammation. Drugs. 2007;67(9):1291-1308. Maastricht, Netherlands.
10. Yonekawa Y, Kim IK. Pseudophakic cystoid macular edema. Curr Opin Ophthalmol. 2012;23(1):26-32. n laura.wielders@mumc.nl
11. Kessel L, Tendal B, Jørgensen KJ, et al. Post-cataract prevention of inflammation and macular edema by steroid and n Financial disclosure: None
nonsteroidal anti-inflammatory eye drops: a systematic review. Ophthalmology. 2014;121(10):1915-1924.
12. Singh R, Alpern L, Jaffe GJ, et al. Evaluation of nepafenac in prevention of macular edema following cataract surgery in
patients with diabetic retinopathy. Clin Ophthalmol. 2012;6:1259-1269.
Bjorn Winkens, PhD
13. Miyanaga M, Miyai T, Nejima R, et al. Effect of bromfenac ophthalmic solution on ocular inflammation following n Department of Methodology and Statistics, Maastricht
cataract surgery. Acta Ophthalmol. 2009;87(3):300-305. University, Maastricht, Netherlands
14. Yavas GF, Ozturk F, Kusbeci T. Preoperative topical indomethacin to prevent pseudophakic cystoid macular edema. J n Financial disclosure: None
Cataract Refract Surg. 2007;33(5):804-807.

MAY 2015 | CATARACT & REFRACTIVE SURGERY TODAY EUROPE  53