A JOURNAL REVIEW ON

TREATMENT OF MACULAR EDEMA

Why is MACULA so prone for
edema?
 The structure of the thick fibre layer of Henle
which can absorb large quantities of fluid;
 the avascularity of the central area for the
absence of capillaries which limit absorption ;
 the higher susceptibility of the macula to both
hypoxic and oxidative stress due to thinness of
fovea.
What is macular edema?

 A common cause of visual diminision in a wide variety

of ocular conditions.
 It is a non specific pathologic response to the
disruption to the normal permeability barrier that
protects the retina.
 Macular edema is defined as retinal thickening from
accumulation of fluid within 1 Disc diameter of the
macula.
 It may be focal, diffuse or cystic and is characterized by
extracellular accumulation of fluid, specifically in
Henle’s layer and the inner nuclear layer of retina.
CAUSES OF MACULAR EDEMA
 Retinal vascular disease: diabetic retinopathy, retinal vein occlusion,
hypertensive retinopathy
 Inflammatory disorders: intraocular surgery, uveitic syndromes, laser
procedures
 Choroidal vascular disease: choroidal neovascularization
 Tractional maculopathies: epiretinal membrane, vitreomacular traction
syndromes
 Drug reactions: epinephrine, prostaglandin analogs, nicotinic acid, timolol,
tamoxifen, glitazones
 Inherited retinal dystrophies: retinitis pigmentosa
 Retinal detachment: exudative, rhegmatogenous
 Intraocular tumors: choroidal melanoma
 Optic nerve head abnormalities: diabetic/ hypertensive papillopathy,
neuroretinitis, optic nerve pits/colobomas
 Trauma (blunt/penetrating injuries)
 Idiopathic 
Molecular and cellular alterations leading to
macular edema

 The breakdown of the blood-retinal barrier seems to be

the most important mechanism in explaining the
extravasation of fluid although similar changes to the
retinal blood flow may play a role.
 In general, an increase in passive permeability through
the endothelium can occur via three general
mechanisms:
1. dysfunction of the intercellular junctions
2. increased transcellular transport
3. increased endothelial cell destruction
 DIAGNOSIS
 Direct Ophthalmoscopy
 Indirect Ophthalmoscopy
 Biomicroscopic slit-lamp examination
 Fluorescein angiography

 Hiedelberg Retina Angiograph 2

  Vitreous fluorometry
 Optical coherence tomography (OCT) &
Retinal thickness analysis (RTA)

OCT showing sponge like

diabetic macular edema

OCT showing cystoid

diabetic macular edema
Folia Med (Plovdiv). 2010 Jan-Mar;52(1):40-8.

Optical coherence tomography for the detection of early

macular edema in diabetic patients with retinopathy.
Koleva-Georgieva DN, Sivkova NP.
AIM: To compare the retinal thickness measurements with spectral-domain optical coherence tomography
(OCT) in healthy subjects with those of type 2 diabetes patients with or without diabetic retinopathy (DR) and
with no clinical evidence of diabetic macular edema (DME).
PATIENTS AND METHODS: The present prospective study included 29 diabetic patients (57 eyes) with no DR
(group 1), 32 diabetic patients (63 eyes) with DR (group 2) and 25 healthy volunteers (39 eyes, control group).
Eyes showing macular edema on slit-lamp biomicroscopy or leakage on fluorescein angiography were not
included in the study. The mean retinal thickness at the central fixation point (CFP) and the 9 ETDRS macular
regions were compared in subgroups of healthy volunteers by age, sex and right or left eye. These mean retinal
thickness values were also compared in the control group, group 1 and group 2.Early DME was diagnosed with
OCT if it exceeded the mean thickness +2.SD (standard deviation) in healthy subjects.
RESULTS: Mean retinal thickness at the CFP and fovea in healthy eyes was 176 +/- 16.8 microm and 198.3 +/-
21.4 microm, respectively. It was significantly greater in men than in women (p < 0.05), decreased with age and
showed no statistically significant difference between right and left eyes. Differences in retinal thickness were
found to be significant for the CFP and all ETDRS regions (controls vs. group 1 and controls vs. group 2) and for
the CFP, fovea, superior inner, temporal inner and nasal inner ETDRS regions (group 1 vs. group 2, group 2
having greater thickness). Early DME was diagnosed at retinal thickness exceeding 209.6 microm at the CFP
and 241.1 microm at the fovea in 13 eyes of diabetic patients from group 2. Twelve eyes with early DME had
mild non-proliferative DR and one--moderate non-proliferative DR.
CONCLUSION: In the present study, mean retinal thickness was greater in diabetic patients (with
and without DR) than in healthy subjects. Patients with DR had thicker retinas than patients
without DR. Spectral-domain OCT seemed to be useful for the detection of early DME in patients
with retinopathy and no clinical evidence of macular edema. Patients with early DME should have
a closer follow-up.
Invest Ophthalmol Vis Sci. 2010 Mar 31. [Epub ahead of print]

Detection of Cystoid Macular Edema with Three-Dimensional Optical

Coherence Tomography versus Fluorescein Angiography.
 Ouyang Y, Keane PA, Sadda SR, Walsh AC.
 Purpose: To compare the sensitivity and reproducibility of three-dimensional optical coherence
tomography (3D-OCT) and fluorescein angiography (FA) for the detection of cystoid macular
edema (CME).
 Methods: Data from all patients who underwent digital FA (Topcon 50IX, Topcon Corp.) and
512x128 horizontal raster 3D-OCT scans (3D-OCT-1000, Topcon Corp.) on the same day in a
retina subspecialty clinic were retrospectively collected. Images were reviewed independently
by four reading center graders and adjudicated as a group to render a single result for each eye
and each imaging modality. Kappa statistics were used to determine the level of agreement
between graders for each modality. The sensitivity of each imaging modality for CME detection
was calculated using the presence of CME on either modality as the ground truth; subgroup
analysis was performed according to disease diagnosis and lens status.
 Results: 413 eyes of 207 patients were included in the analysis. Inter-grader agreement was
higher for 3D-OCT than for FA both before (kappaOCT = 0.61, kappaFA = 0.43) and after
adjudication (kappaOCT = 0.74, kappaFA = 0.58).The sensitivity for detection of definite CME
was higher for 3D-OCT (95%, 144/151 cases) than for FA (44%, 67/151 cases). Definite FA (+) 3D-
OCT (-) CME was seen in 1 eye (0.2%) while definite FA (-) 3D-OCT (+) CME was seen in 40 eyes
(10%). No significant associations between CME detection and lens exam or disease diagnosis
were observed.
 Conclusions: In this study, 3D-OCT was more sensitive and had better
intergrader agreement than FA for the detection of CME.
DIABETIC MACULAR EDEMA
1. Prevention and systemic control

A) Right eye fundus of a 44-year-old type 2 diabetic male with dyslipidemia and increased 24 hours
albuminuria at presentation. OCT line scan shows increased retinal thickness, B) After six weeks of control
i.e. anti-lipid lowering drugs (ATORVASTATIN) and angiotensin receptor blockers (Losartan) for proteinuria,
even before laser photocoagulation, fundus picture and OCT shows decrease in macular edema.
Ophthalmology. 2010 Apr;117(4):766-72. Epub 2010 Jan 4.
Influence of serum lipids on clinically significant versus
nonclinically significant macular edema.
 Raman R, Rani PK, Kulothungan V, Rachepalle SR, Kumaramanickavel G, Sharma T.
 PURPOSE: To estimate the prevalence of diabetic macular edema, both clinically significant macular
edema (CSME) and nonclinically significant macular edema (non-CSME), and report the associations of
dyslipidemia on them.
 DESIGN: A population-based cross-sectional study in India.
 PARTICIPANTS: After all exclusions, 1414 subjects with diabetes underwent an examination.
 METHODS: The CSME was defined according to the Early Treatment Diabetic Retinopathy Study (ETDRS)
guidelines; stereo digital fundus pairs were studied. The dyslipidemia cases were classified according to
the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III).
 MAIN OUTCOME MEASURES: Prevalence of CSME and non-CSME and association of serum lipids with
them.
 RESULTS: The prevalence was 31.76% (95% confidence interval [CI], 26.04-37.47) for overall diabetic
macular edema, 25.49% (95% Ci, 20.14-30.84) for non-CSME, and 6.27% (95% Ci, 3.29-9.24) for CSME.
Univariate analysis identified macroalbuminuria and microalbuminuria, poor glycemic control, high total
serum cholesterol, high serum low-density lipoprotein (LDL) cholesterol, and high serum non-high-
density lipoprotein (HDL) cholesterol related to non-CSME and CSME (trend chi-square test, P<0.05).
Logistic regression analysis (after adjusting variables such as age, gender, body mass index, duration,
smoking, hypertension, glycosylated hemoglobin, macroalbuminuria and microalbuminuria, and insulin
use) revealed high serum LDL cholesterol (odds ratio [OR], 2.72], high serum non-HDL cholesterol (OR,
1.99), and high cholesterol ratio (OR, 3.08) related to non-CSME, and poor glycemic control (OR, 8.06),
microalbuminuria (OR, 14.23), and high serum total cholesterol (OR, 9.09) related to CSME.
 One third of the subjects had diabetic macular edema, and 6% of them
CONCLUSIONS:

showed evidence of CSME necessitating laser photocoagulation. 

Ophthalmology. 2009 Mar;116(3):497-503. Epub 2009 Jan 22.
The Wisconsin Epidemiologic Study of Diabetic Retinopathy XXIII: the twenty-
five-year incidence of macular edema in persons with type 1 diabetes.
 Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BE.
 OBJECTIVE: To examine the 25-year cumulative incidence of macular edema (ME) and its relation to various
risk factors.
 DESIGN: Population-based study.
 PARTICIPANTS: A total of 955 insulin-taking persons living in an 11-county area in southern Wisconsin with
type 1 diabetes diagnosed before age 30 years who participated in baseline examinations (1980-1982) and at
least 1 of 4 follow-up (4-, 10-, 14-, and 25-year) examinations (n=891) or died before the first follow-up
examination (n=64).
 METHODS: Stereoscopic color fundus photographs were graded using the modified Airlie House
classification and the Early Treatment Diabetic Retinopathy Study retinopathy severity scheme. Competing
risk of death was included in statistical models.
 MAIN OUTCOME MEASURES: Incidence of ME and clinically significant ME (CSME).
 RESULTS: The 25-year cumulative incidence was 29% for ME and 17% for CSME. Annualized incidences of ME
were 2.3%, 2.1%, 2.3%, and 0.9% in the first, second, third, and fourth follow-up periods of the study,
respectively. In univariate analyses, the incidence of ME was associated with male sex, more severe diabetic
retinopathy, higher glycosylated hemoglobin, proteinuria, higher systolic and diastolic blood pressure, and
more pack-years of smoking. Multivariate analyses showed that the incidence of ME was related to higher
baseline glycosylated hemoglobin (hazard ratio [HR] per 1% 1.17; 95% confidence interval [CI], 1.10-1.25;
P<0.001) and higher systolic blood pressure (HR per 10 mmHg 1.15; 95% CI, 1.04-1.26; P=0.004) and
marginally to proteinuria (HR 1.43; 95% CI, 0.99-2.08; P=0.06).
 CONCLUSIONS: These data show that relatively high 25-year cumulative rates of
incidence of ME were related to glycemia and blood pressure. The lower risk of
incident ME in the last period of the study may reflect recent improvement in care.
2. Laser photocoagulation
1. FOCAL LASER
2. GRID LASER
Bratisl Lek Listy. 2009;110(7):419-22.
The effect of photocoagulation on visual acuity in diabetic patients
suffering from diabetic macular edema and diabetic retinopathy.
 Ilavska M.
 The aim of the study was to evaluate the effect of photocoagulation and range of
treatment on visual acuity (VA) in patients with diabetic macular edema.
 MATERIAL AND METHOD: 56 patients with type II diabetes mellitus--109 eyes were
divided into four groups depending on the type of treatment. The evidence of macular
edema based on biomicroscopic evaluation or fluorescein angiography was the criterion of
the need to start with photocoagulation. VA was evaluated every 6 months up to 3 years
after the treatment.
 RESULTS: In the first group, 54 eyes were treated by focal photocoagulation. VA was
stabilized in 45 (83.3%), improved in 3 (5.6%), and in 6 (11.1%) eyes became worse. In the
second group, 7 eyes were treated by grid photocoagulation. VA was stabilized in 6 (85.7%)
eyes, and 1 (14.3%) eye got worse. In the third group, 29 eyes were treated with
combination of the direct treatment in macular region with panretinal photocoagulation
(PRP). In the latter group, VA was stabilized in 22 (75.9%) eyes, improved in 3(10.3%), and
in 4 (13.8%) eyes it got worse. In the fourth group, 19 eyes were treated with a
combination of grid photocoagulation and PRP. VA was stabilized in 16 (84.2%), improved
in 2 (10.5%) eyes, and got worse in 1 (5.3%) eye.
 CONCLUSION: Results of this study affirm the benefit of photocoagulation
for keeping the visual acuity. Reasonable range and correct timing of
treatment are indispensable.
Retina. 2009 Nov-Dec;29(10):1436-43.
The course of response to focal/grid photocoagulation for diabetic
macular edema.
 Diabetic Retinopathy Clinical Research Network.
 PURPOSE: The purpose of this study was to determine whether eyes with center-involved diabetic
macular edema, treated with focal/grid photocoagulation, in which there is a reduction in central
subfield thickness (CST) measured with optical coherence tomography after 16 weeks, will
continue to improve if retreatment is deferred.
 METHODS: This is a prospective, multicenter, observational, single-group focal/grid
photocoagulation study of 122 eyes with center-involved diabetic macular edema (optical
coherence tomography CST > or =250 microm). At the 16-week visit and continuing every 8
weeks, eyes were assessed for retreatment and additional laser treatment was deferred if the
visual acuity letter score improved > or =5 letters or optical coherence tomography CST decreased
> or =10% compared with the visit 16 weeks prior.
 RESULTS: Of the 115 eyes that completed the 16-week visit, 54 (47%) had a decrease in CST by >
or =10% compared with baseline. Of these, 26 (48%) had a CST > or =250 microm at 16 weeks and
were evaluable at 32 weeks. Eleven (42%; 95% confidence interval, 23-63%) of the 26 eyes had a
further decrease in CST > or =10% from 16 weeks to 32 weeks without further treatment.
 CONCLUSION: Sixteen weeks after focal/grid laser for diabetic
macular edema in eyes with a definite reduction, but not
resolution, of central edema, 23% to 63% likely will continue to
improve without additional treatment.
Am J Ophthalmol. 2010 Jan;149(1):133-9. Epub 2009 Oct 28.
Subthreshold micropulse diode laser photocoagulation for diabetic macular
edema in Japanese patients.
 Ohkoshi K, Yamaguchi T.
 PURPOSE: To assess the efficacy and safety of subthreshold micropulse diode laser photocoagulation for
diabetic macular edema (ME).
 DESIGN: Prospective, nonrandomized interventional case series.
 METHODS: SETTING: Institutional. PATIENTS: Thirty-six consecutive diabetic patients (43 eyes) with
clinically significant ME and a central macular thickness (CMT) <600 microm by optical coherence
tomography.
 OBSERVATION PROCEDURES: Subthreshold micropulse diode laser photocoagulation was done with a
15% duty cycle (0.2 to 0.3 sec; 200 microm) at 50% to 90% of the burn threshold energy. The treated area
was monitored on color images for 12 months.
 MAIN OUTCOME MEASURES: CMT, best-corrected visual acuity (BCVA), and total macular volume at 3
months.
 RESULTS: After 3 months, there was a significant reduction of CMT (P = .05, paired t test), but the changes
of BCVA and macular volume were not significant. The preoperative CMT, BCVA (logarithm of the minimal
angle of resolution; logMAR), and macular volume were 341.8 +/- 119.0 microm, 0.12 +/- 0.20, and 8.763 +/-
1.605 mm(3) respectively, vs 300.7 +/- 124.1 microm, 0.12 +/- 0.21, and 8.636 +/- 1.408 mm(3) at 3 months.
CMT decreased significantly from 1 month (P = .015, Friedman test). Visual acuity was improved or
maintained within 0.2 logMAR for 12 months in 94.7% of the patients. No obvious laser scars were detected
in any patient.
 CONCLUSIONS: In patients with moderate diabetic ME, subthreshold micropulse
diode laser photocoagulation controls ME and maintains visual acuity with minimal
retinal damage. These findings confirm the efficacy of this method for Japanese
patients.
 3. Vitrectomy
 Indications of vitrectomy in DME includes
1. Diffuse macular edema with taut posterior hyaloid
membrane (TPHM)
2. Recalcitrant diffuse macular edema without TPHM

A 60-year-old diabetic with 20/400 vision with PRP and grid laser scars in the left eye (A), OCT shows
taut posterior hyaloid with increased retinal thickness (B). Patient underwent Pars plana Vitrectomy
(PPV) with TPHM removal. Four weeks after surgery OCT shows normal foveal contour (C).
Ophthalmology. 2010 Mar 16. [Epub ahead of print]
Vitrectomy Outcomes in Eyes with Diabetic Macular Edema and Vitreomacular
Traction.
 Diabetic Retinopathy Clinical Research Network( ⁎) Writing Committee on behalf of the DRCR.net .
 PURPOSE: To evaluate vitrectomy for diabetic macular edema (DME) in eyes with at least moderate vision loss and
vitreomacular traction.
 DESIGN: Prospective cohort study. PARTICIPANTS: The primary cohort included 87 eyes with DME and
vitreomacular traction based on investigator's evaluation, visual acuity 20/63-20/400, optical coherence
tomography (OCT) central subfield >300 microns and no concomitant cataract extraction at the time of vitrectomy.
METHODS: Surgery was performed according to the investigator's usual routine. Follow-up visits were performed
after 3 months, 6 months (primary end point), and 1 year.
 MAIN OUTCOME MEASURES: Visual acuity, OCT retinal thickening, and operative complications.
 RESULTS: At baseline, median visual acuity in the 87 eyes was 20/100 and median OCT thickness was 491 microns.
During vitrectomy, additional procedures included epiretinal membrane peeling in 61%, internal limiting membrane
peeling in 54%, panretinal photocoagulation in 40%, and injection of corticosteroids at the close of the procedure in
64%. At 6 months, median OCT central subfield thickness decreased by 160 microns, with 43% having central
subfield thickness <250 microns and 68% having at least a 50% reduction in thickening. Visual acuity improved by
>/=10 letters in 38% (95% confidence interval, 28%-49%) and deteriorated by >/=10 letters in 22% (95% confidence
interval, 13%-31%). Postoperative complications through 6 months included vitreous hemorrhage (5 eyes), elevated
intraocular pressure requiring treatment (7 eyes), retinal detachment (3 eyes), and endophthalmitis (1 eye). Few
changes in results were noted between 6 months and 1 year.
 CONCLUSIONS: After vitrectomy performed for DME and vitreomacular traction, retinal thickening
was reduced in most eyes. Between 28% and 49% of eyes with characteristics similar to those
included in this study are likely to have improvement of visual acuity, whereas between 13% and
31% are likely to have worsening. The operative complication rate is low and similar to what has
been reported for this procedure. These data provide estimates of surgical outcomes and serve as a
reference for future studies that might consider vitrectomy for DME in eyes with at least moderate
vision loss and vitreomacular traction.
4. STEROIDS – IVTA (Triamcinolone acetonide )
 Ophthalmology. 2009 May;116(5):902-11; quiz 912-3.
Intravitreal triamcinolone acetonide injection for treatment of
refractory diabetic macular edema: a systematic review.
 Yilmaz T, Weaver CD, Gallagher MJ, Cordero-Coma M, Cervantes-Castaneda RA, Lavaque AJ, Larson RJ.
 OBJECTIVE: To compare intravitreal triamcinolone acetonide (IVTA) injection versus no treatment or
sub-Tenon triamcinolone acetonide (STTA) injection in improving visual acuity (VA) of patients with
refractory diabetic macular edema (DME; unresponsive to focal laser therapy).
 CLINICAL RELEVANCE: Diabetic macular edema is the leading cause of visual loss in diabetic
retinopathy. Laser therapy has been the standard of care for patients with persistent or progressive
disease. More recently, it has been suggested that IVTA injection may improve VA.
 METHODS AND LITERATURE REVIEWED: The following databases were searched: Medline (1950-
September Week 2 2008), The Cochrane Library (Issue 3, 2008), and the TRIP Database (up to
September 1, 2008), using no language or other limits. Randomized controlled trials were included that
consisted of patients with refractory DME, those comparing IVTA injection with no treatment or STTA
injection, those reporting VA outcomes, and those having a minimum follow-up of 3 months.
 RESULTS: In the 4 randomized clinical trials comparing IVTA injection with placebo or no treatment,
IVTA injection demonstrated greater improvement in VA at 3 months, but the benefit was no longer
significant at 6 months. Those who received IVTA injection had significantly higher IOP at 3 months and
at 6 months. In the 2 randomized clinical trials comparing IVTA injection with STTA injection, IVTA
injection demonstrated greater improvement in VA at 3 months, but not at 6 months. Intravitreal
triamcinolone acetonide injection demonstrated no difference in IOP at 3 months or at 6 months.

Intravitreal triamcinolone acetonide injection is effective in
CONCLUSIONS:

improving VA in patients with refractory DME in the short-term, but

the benefits do not seem to persist in the long-term.
Ophthalmologica. 2010 Feb 17;224(4):258-264. [Epub ahead of print]
Comparison of Intravitreal Bevacizumab versus Triamcinolone for the
Treatment of Diffuse Diabetic Macular Edema.

 Kreutzer TC, Al Saeidi R, Kook D, Wolf A, Ulbig MW, Neubauer AS, Haritoglou C.

 Background: Our purpose was to compare the effect of triamcinolone and bevacizumab (Avastin) on the
retinal thickness and functional outcome in patients with diabetic macular edema.
 Methods and Materials: A collective of 32 patients, who had been treated by a single 4.0-mg intravitreal
triamcinolone injection (group 1), was matched to 32 patients ('matched pairs'), who had received 3
injections of 1.25 mg of bevacizumab within 3 months in 4-week intervals (group 2). The outcome
variables were changes in best corrected visual acuity (VA) and central retinal thickness 3 months after
therapy.
 Results: Both groups did not differ regarding preoperative VA and central retinal thickness measured by
optical coherence tomography. The baseline mean VA was 0.72 +/- 0.39 logMAR in group 1 and 0.73 +/-
0.39 logMAR in group 2 (p = 0.709). The mean central retinal thickness measured by optical coherence
tomography was 548 +/- 185 mum in group 1 and 507 +/- 192 mum in group 2. While the patients in
group 1 experienced a slight increase in VA of on average 0.7 lines following a single triamcinolone
injection to a mean of 0.64 +/- 0.40 logMAR (p = 0.066) after 3 months, the patients in group 2 showed
almost no effect on VA with an average increase of 0.2 lines to a mean VA of 0.72 +/- 0.30 logMAR (p =
0.948) following 3 intravitreal injections of bevacizumab. Comparing the effect on VA between both
groups no statistically significant difference (p = 0.115) was noted. Concerning decrease in central retinal
thickness both therapies were highly effective (p < 0.001 each), again, without statistically significant
difference between the groups (p < 0.128).
 Conclusion: Our data suggest that a single triamcinolone injection may be as effective
as a 3 times repeated intravitreal administration of bevacizumab for the treatment of
diabetic macular edema. Further prospective trials should be performed. 
 5.Anti-VEGF Therapies

 Three drugs are currently in use.

 Bevacizumab (Avastin) was approved by the FDA for intravenous use in
cancer patients. This drug has been used off-label as an intravitreal
injection, first for AMD, and subsequently for a variety of other ocular
diseases including macular edema.
Dose : 1.25 mg, 2.5 mg / 0.05 ml
 Ranibizumab (Lucentis) is FDA-approved for intravitreal injection in
patients with AMD, and has been used off-label for other ocular
diseases including diabetic macular edema.
Dose : 0.3 mg, 0.5 mg
 Pegaptanib (Macugen) was FDA-approved for intravitreal injection in
patients with AMD before the advent of ranibizumab and bevacizumab.
Dose : 0.3 mg, 1 mg, and 3mg
Ophthalmology. 2009 Aug;116(8):1488-97, 1497.e1. Epub 2009 Jul 9.
Primary intravitreal bevacizumab for diffuse diabetic macular edema: the
Pan-American Collaborative Retina Study Group at 24 months.
 Arevalo JF, Sanchez JG, Wu L, Maia M, Alezzandrini AA, Brito M, Bonafonte S, Lujan S, Diaz-Llopis M, Restrepo N, 
Rodríguez FJ, Udaondo-Mirete P; Pan-American Collaborative Retina Study Group.
 PURPOSE: To report the 24-month anatomic and Early Treatment Diabetic Retinopathy Study (ETDRS) best-
corrected visual acuity (BCVA) response after primary intravitreal bevacizumab (Avastin; Genentech, Inc., San
Francisco, CA; 1.25 or 2.5 mg) in patients with diffuse diabetic macular edema (DDME). In addition, a comparison of
the 2 different doses of intravitreal bevacizumab (IVB) used is presented.
 DESIGN: Retrospective, multicenter, interventional, comparative case series.
 PARTICIPANTS: The clinical records of 115 consecutive patients (139 eyes) with DDME at 11 centers from 8
countries were reviewed. METHODS: Patients were treated with at least 1 intravitreal injection of 1.25 or 2.5 mg of
bevacizumab. All patients were followed up for 24 months. Patients underwent ETDRS BCVA testing,
ophthalmoscopic examination, optical coherence tomography (OCT), and fluorescein angiography (FA) at the
baseline, 1-, 3-, 6-, 12-, and 24-month visits.
 MAIN OUTCOME MEASURES: Changes in BCVA and OCT results.
 RESULTS: The mean age of the patients was 59.4+/-11.1 years. The mean number of IVB injections per eye was 5.8
(range, 1-15 injections). In the 1.25-mg group at 1 month, BCVA improved from 20/150 (0.88 logarithm of the
minimum angle of resolution [logMAR] units) to 20/107, 0.76 logMAR units (P<0.0001). The mean BCVA at 24
months was 20/75 (0.57 logMAR units; P<0.0001). Similar BCVA changes were observed in the 2.5-mg group: at 1
month, BCVA improved from 20/168 (0.92 logMAR units) to 20/118 (0.78 logMAR units; P = 0.02). The mean BCVA
at 24 months was 20/114 (0.76 logMAR units; P<0.0001). In the 1.25-mg group, the mean central macular thickness
(CMT) decreased from 466.5+/-145.2 microm at baseline to 332.2+/-129.6 micromat 1 month and 286.6+/-81.5
microm at 24 months (P<0.0001). Similar results were obtained in the 2.5-mg group.
 CONCLUSIONS: Primary IVB at doses of 1.25 to 2.5 mg seem to provide
stability or improvement in BCVA, OCT, and FA in DDME at 24 months. The
results show no evident difference between IVB at doses of 1.25 or 2.5 mg.
6.Sustained-release
corticosteroid delivery devices
 Retisert (fluocinolone acetonide) is an
intraocular implant that delivers 0. 59 mg of
fluocinolone acetonide to the posterior segment
up to 3 years.
 Posurdex (dexamethasone) is another sustained
delivery intraocular implant that has been found
to improve visual acuity in eyes with persistent
macular edema at a dose of 700 mcg compared
with observation through 6 months.
 Ophthalmology. 2010 Mar 2. [Epub ahead of print]
Sustained Ocular Delivery of Fluocinolone Acetonide by an
Intravitreal Insert.
 Campochiaro PA, Hafiz G, Shah SM, Bloom S, Brown DM, Busquets M, Ciulla T, Feiner L, Sabates N, Billman
K, Kapik B, Green K, Kane F; Famous Study Group(⁎).
 PURPOSE: To compare Iluvien intravitreal inserts that release 0.2 or 0.5 mug/day of fluocinolone acetonide
(FA) in patients with diabetic macular edema (DME).
 DESIGN: Prospective, randomized, interventional, multicenter clinical trial.
 PARTICIPANTS: We included 37 patients with DME.
 METHODS: Subjects with persistent DME despite >/=1 focal/grid laser therapy were randomized 1:1 to
receive an intravitreal insertion of a 0.2- or a 0.5-mug/day insert.
 MAIN OUTCOME MEASURES: The primary end point was aqueous levels of FA throughout the study with an
important secondary outcome of the change from baseline in best-corrected visual acuity (BCVA) at month
12.
 RESULTS: The mean aqueous level of FA peaked at 3.8 ng/ml at 1 week and 1 month after administration of a
0.5-mug/day insert and was 3.4 and 2.7 ng/ml 1 week and 1 month after administration of a 0.2-mug/day
insert. For both inserts, FA levels decreased slowly thereafter and were approximately 1.5 ng/ml for each at
month 12. The mean change from baseline in BCVA was 7.5, 6.9, and 5.7 letters at months 3, 6, and 12,
respectively, after administration of a 0.5 mug/day-insert and was 5.1, 2.7, and 1.3 letters at months 3, 6, and
12, respectively, after administration of a 0.2-mug/day insert. There was a mild increase in mean intraocular
pressure after administration of 0.5-mug/day inserts, but not after administration of 0.2-mug/day inserts.
 CONCLUSIONS: The FA intravitreal inserts provide excellent sustained intraocular release
of FA for >/=1 year. Although the number of patients in this trial was small, the data
suggest that the inserts provide reduction of edema and improvement in BCVA in patients
with DME with mild effects on intraocular pressure over the span of 1 year. 
7.OTHER GROWTH FACTOR MODULATORS

 Activated protein kinase C has been associated with

increased levels of VEGF and is also implicated in
increased retinal vascular permeability.
 PKC412 is an oral kinase inhibitor that was found to
reduce foveal thickening by 66. 7 mcm at doses of 100-
150 mg/d compared with placebo with a small but
significant improvement in visual acuity at 3 months.
 Ruboxistaurin, a selective oral protein kinase C beta
inhibitor administered at doses of 4, 16, or 32 mg/d
over 18 months, was also found to reduce retinal
vascular leakage compared with placebo in patients
with severe diabetic macular edema.
8. Miscellaneous therapies

 Other potential targets in the treatment of macular

edema include pigment epithelium-derived factor
and interferon alpha-2a.
 Pigment epithelium-derived factor may interfere with
VEGF-induced vascular permeability and has been
found to occur in lower concentrations in the vitreous
of eyes with DME.
 Supplemental oxygen has also been found to reduce
excess foveolar thickness by 42% and improve visual
acuity by at least 2 lines in a small study of patients
with chronic ME.
Macular edema in Vascular occlusions
 Macular grid laser treatment has been the mainstay of treatment of CME due to
BRVO since the publication of the Branch Vein Occlusion Study (BVOS) in 1984.
 The BVOS demonstrated a clear benefit of grid laser treatment for eyes with
vision of 20/40 or less secondary to macular edema from perfused BRVO.
 Unfortunately, the Central Vein Occlusion Study (CVOS) showed no benefit of
macular grid laser treatment on CME due to CRVO.
 Additionally, not all BRVO eyes are good candidates for laser because it cannot
be applied in eyes with dense intraretinal hemorrhage, and eyes with severe
macular ischemia may actually do better without treatment.
 Accordingly, investigators have looked at other approaches to treat CME due to
BRVO and CRVO, including
 laser-induced chorioretinal anastamosis,
 radial optic neurotomy,
 arteriovenous sheathotomy, and
 therapy with intravitreal steroids or
 anti-vascular endothelial growth factor (VEGF) agents
 Vitrectomy.
Graefes Arch Clin Exp Ophthalmol. 2008 Dec;246(12):1671-6. Epub 2008 Aug 16.
Combined intravitreal triamcinolone injection and laser
photocoagulation in eyes with persistent macular edema after
branch retinal vein occlusion.
 Riese J, Loukopoulos V, Meier C, Timmermann M, Gerding H.
 BACKGROUND: To determine the efficacy of combined intravitreal triamcinolone (TA) injection and laser
photocoagulation in persistent macular edema after branch retinal vein occlusion (BRVO).
 METHODS: Follow-up analysis of a case series of 24 patients with macular edema after BRVO (15 of 24 non-
ischaemic, 9 of 24 ischaemic). Patients received an intravitreal injection of 4 mg TA followed by laser
photocoagulation within the previously edematous area, applied in one or two sessions. Standardized clinical
examinations included best corrected visual acuity testing, anterior and posterior segment biomicroscopy,
intraocular pressure, and optical coherence tomography (OCT). Fluorescein angiography was performed before
treatment and 3 and 6 months later.
 RESULTS: Median visual acuity improved significantly from 0.58 logMAR (95%-confidence interval (KI): 0.54-
0.75, decimal 0.27) at baseline to 0.41 logMAR (KI: 0.37-0.64, decimal 0.39) at 1 month (p = 0.001), 0.33 logMAR
(KI: 0.32-0.62, decimal 0.47) at 3 months (p = 0.002), and 0.41 logMAR (KI: 0.33-0.67, decimal 0.39) at 6 months
(p = 0.016). A gain of one or more logarithmic lines was evaluated in 16/24 eyes (67 %) and a gain of 3 lines or
more in 8/24 eyes (33 %) at 6 months. Three eyes had lost more than 1 line during the follow-up period. Median
change of visual acuity at 6 months was +2.0 lines (KI: 0.2-2.4). Median central foveal thickness (OCT-CFT) was
423 microm (KI: 378-456, n = 24) at baseline and decreased to 270 microm (KI: 249-311, n = 24) at 1 month (p <
0.0001), 265 microm (KI: 254-344, n = 24) at 3 months (p < 0.0001), and 266 microm (KI: 259-365, n = 18) at 6
months (p = 0.001).
 CONCLUSIONS: Macular edema after BRVO can effectively be treated by a
combination of intravitreal TA injection and subsequent laser photocoagulation.
During a 6-month follow-up this combination treatment resulted in a significant
reduction of central foveal thickness and improvement of visual acuity.
 Retina. 2008 Mar;28(3):465-72.
Efficacy of intravitreal triamcinolone for the treatment of macular edema
secondary to branch retinal vein occlusion in eyes with or without grid
laser photocoagulation.
 Cakir M, Dogan M, Bayraktar Z, Bayraktar S, Acar N, Altan T, Kapran Z, Yilmaz OF.

 PURPOSE: To evaluate the efficacy of primary and secondary (following grid laser photocoagulation) intravitreal
triamcinolone acetonide (IVTA) injection for the treatment of macular edema associated with branch retinal vein occlusion
(BRVO).
 METHODS: Eyes with macular edema secondary to BRVO and best-corrected visual acuity (BCVA) worse than 20/40 were
included. Eyes eligible for Branch Retinal Vein Occlusion Study (BVOS) guidelines received grid laser treatment first. Those
that were not improved at least two lines following grid laser or that did not meet those guidelines received 4 mg IVTA
injection. The efficacy of IVTA treatment was assessed by analyzing the change in BCVA and reduction in central macular
thickness (CMT) measured by optical coherence tomography. Intraocular pressure (IOP) spikes and other complications were
recorded.
 RESULTS: The data from 37 eyes were included; in 12 of them IVTA injection was given after grid laser while 25 of them
received IVTA as a primary treatment. Mean follow-up was 9.6 +/- 4.5 months. BCVA was 0.06 +/- 0.30 and 0.17 +/- 0.50 in the
primary and secondary IVTA injection groups, respectively. In the primary injection group, there was a statistically significant
gain in BCVA throughout the follow-up (P < 0.05), while a small increase in BCVA was noted only at the third month visit in the
secondary IVTA injection group (P = 0.04). Average CMT were 434.8 +/- 122.1microm and 389.0 +/- 171.9 microm before IVTA
injection in the two groups, respectively. In the primary IVTA injection group, CMT decreased at 1 month following IVTA
injection and remained statistically significant until the sixth month visit (P < 0.05). In the secondary IVTA injection group, a
slight reduction in CMT was noted only in the first month visit (P = 0.02). Pre-IVTA BCVA was found to be the single
statistically significant predictor of BCVA gain following IVTA injection. In 8 patients (21.6%), the IOP increased above 25
mmHg postoperatively, and was successfully managed by medical treatment. Endophthalmitis did not develop in any of the
patients.
 CONCLUSION: IVTA injection produced a significant reduction of macular edema in eyes with BRVO
either with or without prior grid laser treatment. Reduction of CMT increased the BCVA in most
of the eyes receiving IVTA primarily, while only a slight improvement of BCVA was found in eyes
with prior grid laser. The IVTA effect was transient. Larger studies are necessary to find the best
approach (either grid laser or IVTA) to patients with macular edema associated with BRVO.
Am J Ophthalmol. 2010 Jan;149(1):147-54. Epub 2009 Oct 28.
Pegaptanib sodium for macular edema secondary to branch retinal
vein occlusion.
 Wroblewski JJ, Wells JA 3rd, Gonzales CR.
 PURPOSE: To assess the efficacy and safety of intravitreous pegaptanib sodium (Macugen; EyeTech
Pharmaceuticals/Pfizer Inc, New York, New York, USA) for macular edema secondary to branch
retinal vein occlusion (BRVO).
 DESIGN: Prospective, randomized, dose-finding study.
 METHODS: Twenty subjects from three clinical practices in the United States with BRVO of more
than 1 month's and fewer than 6 months' duration; best-corrected visual acuity (BCVA) 70 to 25 Early
Treatment Diabetic Retinopathy Study letters inclusive (approximately 20/40 to 20/320 Snellen); and
central foveal thickness of 250 microm or more were included. Subjects were randomized 3:1 to
intravitreous injections of pegaptanib 0.3 or 1 mg at baseline and at weeks 6 and 12 with subsequent
injections at 6-week intervals at investigator discretion until week 48. Principal efficacy outcomes
were change from baseline to week 54 in BCVA, center point thickness, central subfield thickness,
and macular volume as measured by optical coherence tomography.
 RESULTS: Fifteen subjects received pegaptanib 0.3 mg and 5 received pegaptanib 1 mg. Eighteen
subjects completed the 54-week follow-up. Results were similar in both the 0.3- and 1-mg groups.
Overall improvements from baseline to week 54 occurred in mean BCVA (+14 +/- 13 letters), center
point thickness (-205 +/- 195 mum), central subfield thickness (-201 +/- 153 mum), and macular
volume (-2.2 +/- 1.6 mm(3)). The response was rapid after the first injection, with a mean BCVA
improvement of 11 +/- 7 letters at 1 week from the baseline of 56 +/- 12 letters (approximately 20/80
Snellen). One retinal detachment and no cases of endophthalmitis or traumatic cataract were seen.
 CONCLUSIONS: Intravitreous pegaptanib offers a promising alternative
as a treatment for macular edema secondary to BRVO . 
Retina. 2009 Oct;29(9):1242-8.
Intravitreal injection of bevacizumab for macular edema secondary to branch
retinal vein occlusion:results after 12 months and multiple regression
analysis.
 Kondo M, Kondo N, Ito Y, Kachi S, Kikuchi M, Yasuma TR, Ota I, Kensaku M, Terasaki H.
 PURPOSE: To evaluate the 12-month follow-up results of intravitreal bevacizumab therapy
for macular edema secondary to branch retinal vein occlusion and to identify the
pretreatment factors that were associated with an improvement of the final visual outcome.
 METHODS: Fifty eyes of 50 patients with macular edema secondary to branch retinal vein
occlusion received an injection of 1.25 mg/0.05 mL bevacizumab. Additional injections were
done when recurrence of macular edema occurred or the treatment was not effective. The
best-corrected visual acuity and foveal thickness were measured. Stepwise multiple
regression analyses were also performed.
 RESULTS: The mean logarithm of the minimum angle of resolution visual acuity improved
significantly from 0.53 to 0.26, and the mean foveal thickness decreased significantly from
523 to 305 microm during the 12-month follow-up period. The mean number of injections
was 2.0 (range, 1-4). Stepwise multiple regression analyses showed that younger patients
had both better visual acuity at 12 months and greater improvement of visual acuity during
12 months. In addition, better pretreatment visual acuity was associated with better visual
acuity at 12 months but with less improvement of the visual acuity.
 CONCLUSION: Intravitreal bevacizumab therapy can be a long-term
effective treatment for macular edema secondary to branch retinal
vein occlusion.
Eur J Ophthalmol 2009; 19: 1056 - 1063
Pars plana vitrectomy with ILM peeling for macular edema secondary
to retinal vein occlusion
 Marzena Raszewska-Steglinska, Piotr Gozdek, Slawomir Cisiecki, Zofia Michalewska, Janusz
Michalewski, Jerzy Nawrocki
 Purpose. To evaluate anatomic and functional results in patients with macular edema in retinal vein
occlusion (RVO), treated with pars plana vitrectomy (PPV) and internal limiting membrane (ILM)
peeling, depending on the timing of surgery.
 Methods. A total of 35 consecutive patients underwent PPV with ILM peeling. Visual acuity, fluorescein
angiography, and optical coherence tomography/spectral optical coherence tomography were
performed preoperatively and 6–12 months postoperatively.
 Results. Anatomic improvement was achieved in 29 patients (82.9%). In 6 patients, there was no
improvement. Central macular thickness decreased in 17 patients (48.6%) with central retinal vein
occlusion (CRVO) and in 12 patients (34.3%) with branch retinal vein occlusion (BRVO) (p<0.05). A total
of 68% of eyes showed improvement in visual acuity (p<0.05). Visual acuity improved in 14 patients
(mean 3.7 Snellen lines) with CRVO and in 10 patients ( mean 3.7 Snellen lines) with BRVO. The t test
shows no statistically significant difference in visual acuity improvement between ischemic and
nonischemic CRVO (p>0.05) or between ischemic and nonischemic BRVO (p>0.05). Better results were
observed in patients treated within 1 month of the onset of symptoms than in patients treated after
more than 1 month. The difference is statistically significant (t test, p=0.0016). 
 Conclusions. PPV with ILM peeling may improve anatomic and functional prognosis in
patients with macular edema secondary to RVO. Vitrectomy with ILM peeling seems to
be beneficial for macular edema secondary to RVO in patients treated within 1 month
from the onset of symptoms. PPV with ILM peeling in ischemic RVO and nonischemic
RVO improves visual acuity.
Korean J Ophthalmol. 2006 Dec;20(4):210-4.
Arteriovenous sheathotomy for persistent macular edema
in branch retinal vein occlusion.
 Sohn JH, Song SJ.
 PURPOSE: To evaluate the efficacy of arteriovenous (AV) sheathotomy with internal
limiting membrane peeling for persistent or recurrent macular edema after intravitreal
triamcinolone injection and/or laser photocoagulation in branch retinal vein occlusion.
 METHODS: Twenty-two eyes with branch retinal vein occlusion (BRVO) with recurrent
macular edema underwent vitrectomy with AV sheathotomy and internal limiting
membrane peeling. All eyes had previous intravitreal triamcinolone injection and/or
laser photocoagulation for macular edema. The best corrected visual acuity (BCVA),
fluorescein angiography and optical coherence tomography (OCT) before and after
surgery were compared.
 ESULTS: The mean preoperative BCVA (log MAR) were 0.79 +/- 0.29 and postoperative
BCVA (log MAR) at 3 months was 0.57 +/- 0.33. And improvement of visual acuity > or =
2 lines was observed in 10 eyes (45%). The mean preoperative fovea thickness
measured by OCT was 595.22 +/- 76.83 microm (510-737 microm) and postoperative
fovea thickness was 217.60 +/- 47.33 microm (164-285 microm).
 CONCLUSIONS: Vitrectomy with AV sheathotomy can be one
treatment option for the patients with recurrent macular
edema in BRVO.
Cystoid Macular Edema
Non-steroidal Anti-
inflammatory Drugs (NSAIDs)
 CME develops, in part, because of a prostaglandin-induced breach
of the blood-retinal barrier and, subsequently, secondary retinal
edema.
 Topical NSAIDs inhibit the production of prostaglandins by affecting
the cyclooxygenase enzyme.
 NSAIDs also target other inflammatory mediators that are
responsible for edema formation and have been investigated in the
prophylaxis and therapy of postsurgical cystoid macular edema.
 Numerous studies have determined that NSAIDs are effective in the
treatment of pseudophakic CME, including Ketorolac
tromethamine 0.5%, Diclofenac sodium 0.1%, Nepafenac 0.1% and
Bromfenac 0.09%.
Retina. 2010 Feb;30(2):260-6.
NSAIDs in combination therapy for the treatment of chronic pseudophakic
cystoid macular edema.
 Warren KA, Bahrani H, Fox JE.
 PURPOSE: The purpose of this study was to evaluate the addition of topical nonsteroidal
antiinflammatory drugs (NSAIDs) to intravitreal corticosteroid and antivascular endothelial growth
factor injections for the treatment of chronic cystoid macular edema.
 METHODS: Thirty-nine patients with chronic pseudophakic cystoid macular edema completed a
single-center, randomized, investigator-masked study. All patients were treated with an intravitreal
triamcinolone and bevacizumab injection at study entry; the bevacizumab injection was repeated at 1
month. To evaluate the effect of adding an NSAID, patients were randomized to treatment with 1 of 4
topical NSAIDs (diclofenac 0.1%, ketorolac 0.4%, nepafenac 0.1%, and bromfenac 0.09%) or placebo
for 16 weeks.
 RESULTS: At Weeks 12 and 16, both the nepafenac and bromfenac groups showed a significant
reduction in retinal thickness compared with that in placebo (nepafenac, P = 0.0048, bromfenac, P =
0.0113). A difference, however, between these 2 NSAID groups was observed in that only the
nepafenac group was able to maintain the demonstrated retinal thickness decrease at Weeks 12 and
16. The nepafenac group also experienced a significant improvement in visual acuity at Weeks 12 (P =
0.0084) and 16 (P = 0.0233). The addition of NSAIDs did not produce an increase in mean intraocular
pressure over the course of therapy.
 CONCLUSION: Although NSAID therapy seems to potentiate the improvements
produced by corticosteroids and antivascular endothelial growth factor therapy for
chronic pseudophakic cystoid macular edema, only nepafenac- and bromfenac-
treated eyes showed reduced retinal thickness at 12 weeks and 16 weeks.
Furthermore, nepafenac produced a sustained improvement in visual acuity.
CARBONIC ANHYDRASE INHIBITORS
 The rationale of carbonic anhydrase inhibitors as a therapeutic
agent in the treatment of macular edema is to improve the
ability of retinal pigment epithelial cells to pump fluid out of
the retina.
 Carbonic anhydrase inhibitors may alter the polarity of the
ionic transport systems in the retinal pigment epithelium
through the inhibition of carbonic anhydrase and γ-glutamyl
transferase. As a result there is increased fluid transport across
the retinal pigment epithelium from the sub-retinal space to
the choroid with reduction of the edema.
 Acetazolamide (Diamox) has been found to be particularly
beneficial in patients in the treatment of uveitic CME,
pseudophakic CME and in macular edema due to retinitis
pigmentosa.
 Dose is 500 mg/day, which should be continued for at least 1
month to see an effect.
Eur J Ophthalmol. 2008 Nov-Dec;18(6):1011-3.
Pseudophakic macular edema and oral acetazolamide: an optical coherence
tomography measurable, dose-related response.

 Ismail RA, Sallam A, Zambarakji HJ.

 PURPOSE: Although uncommon after phacoemulsification surgery, cystoid macular edema
(CME) is an important cause of postoperative reduction of vision after cataract surgery. To
demonstrate an optical coherence tomography (OCT) measurable, dose-related response to
orally administered acetazolamide in a patient presenting with pseudophakic CME.
 METHODS: A 76-year-old woman with reduced vision in right eye due to cataract had
uneventful phacoemulsification. Surgery was complicated by early onset endophthalmitis
that was treated with intravitreal antibiotics with good visual recovery. At 6 months follow-
up, she presented with further reduction of vision (0.5 LogMAR) due to CME and a central
foveal thickness (CFT) of 587 microm.
 RESULTS: Acetazolamide treatment was started in combination with topical ketorolac. At a
daily dose of 500 mg, CFT and visual acuity were 262 microm and 0.34 LogMAR,
respectively. Dose reduction of acetazolamide to 250 mg/day was associated with
worsening of the CFT to 335 microm. CFT was subsequently measured at 230 microm on
increasing the acetazolamide dose to 500 mg/day and measured 353 microm when
acetazolamide dose was halved. CFT was 478 microm when acetazolamide was ceased.
 CONCLUSIONS. In this report, the authors have shown a dose-related response of
pseudophakic CME to oral acetazolamide. This would suggest that the clinical response
to oral acetazolamide may be titrated to the extent of CME and monitored by OCT.
J Ocul Pharmacol Ther. 2010 Apr;26(2):199-206.
Intravitreal bevacizumab versus triamcinolone acetonide for refractory
uveitic cystoid macular edema: a randomized pilot study.

 Soheilian M, Rabbanikhah Z, Ramezani A, Kiavash V, Yaseri M, Peyman GA.

 PURPOSE: To compare intravitreal bevacizumab (IVB) versus intravitreal triamcinolone
acetonide (IVT) for treatment of refractory uveitic cystoid macular edema (CME).
 METHODS: In this randomized clinical trial, 31 eyes with uveitic CME were allocated into
the IVB group-eyes that received 1-3 injections of 1.25 mg bevacizumab (15 eyes) and the
IVT group-eyes that received 1-3 injections of 2 mg triamcinolone (16 eyes). Primary
outcome measure was change in best-corrected visual acuity (VA) at 36 weeks.
 RESULTS: Visual acuity improvement compared with baseline values was meaningful in
the IVB group at 12, 24, and 36 weeks (-0.35 + or - 0.45 logMAR [P = 0.016]) and in the IVT
group at 24 and 36 weeks (-0.32 + or - 0.32 logMAR [P = 0.001]). A significant central
macular thickness (CMT) reduction was observed only in the IVT group at week 36 (74.6 +
or - 108.0 microm [P = 0.049]). Between-group analysis disclosed no significant
difference in any outcome measure. By statistically removing the factor of cataract, the
IVT group had more improvement in VA (P = 0.007).
 CONCLUSIONS: IVB was as effective as IVT in refractory uveitic
CME regarding VA improvement up to 36 weeks. Irrespective of
triamcinolone-induced cataract, a more beneficial effect of IVT
may be attainable.
Asian J Ophthalmol,Volume 148, Issue 2, Pages 303-309.e2 (August 2009)
Ranibizumab for Refractory Uveitis-related Macular Edema

 Nisha R. Acharyaab, Kevin C. Honga, Salena M. Leea

 Purpose To evaluate the effect of intravitreal ranibizumab injections (Lucentis; Genentech Inc,
South San Francisco, California, USA) on refractory cystoid macular edema (CME) in patients with
controlled uveitis who have failed oral and regional corticosteroid treatment, the mainstays of
current medical therapy.
 Design Prospective, noncomparative, interventional case series.
 Methods Seven consecutive patients with controlled uveitis and refractory CME who had failed
corticosteroid treatment were studied. One eligible patient chose not to participate and another
did not complete follow-up for nonmedical reasons. Intravitreal ranibizumab injections (0.5 mg)
were given monthly for 3 months, followed by reinjection as needed. The primary outcome was
the mean change in best spectacle-corrected visual acuity (VA) from baseline to 3 months, and
the secondary objective was the mean change in central retinal thickness (CRT) on ocular
coherence tomography. Six-month outcomes were also assessed.
 Results At 3 months, the mean increase in acuity for the 6 patients who completed follow-up was
13 letters (2.5 lines), and the mean decrease in CRT was 357 μm. Both VA and CRT improved
significantly between baseline and 3 months (P = .03 for each). Although most patients required
reinjection, this benefit was maintained at 6 months. There were no significant ocular or systemic
adverse effects.
 Conclusions Intravitreal ranibizumab led to an increase in VA and
regression of uveitis-associated CME in patients refractory to or intolerant
of standard corticosteroid therapy. Further studies of this promising
treatment are warranted.
Stepwise Approach for Treating
CME (IRVINE GASS SYNDROME)
 Step 1 Wait and watch
Topical NSAIDs
 Step 2 Topical Corticosteroids
 Step 3 Sub-tenon steroid injection
 Step 4 Oral Acetazolamide (Diamox)
Oral Corticosteroid
 Step 5 Laser Nd-YAG vitreolysis
Vitrectomy
 Conclusion
 Macular edema is a condition of enormous medical and
socioeconomic importance because of its high prevalence and
occurrence in a large number of pathologic conditions.
 It is the endpoint of a variety of pathophysiologic processes that can
be effectively managed by recognizing and addressing the
pathogenic factors that are operative in a given clinical setting.
 So far, there are no clear guidelines for the treatment of subclinical
cystoid macular edema and every practitioner has their own
strategy using a variety of pharmacologic agents, as well as vitreous
surgery when needed.
 Although treatment options continue to expand with the
development of new drugs and surgical procedures, long-term
efficacy and safety of most new approaches have yet to be
established in controlled clinical trials.
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