Original Paper


Received: August 25, 2013 Accepted: February 23, 2014 Published online: August 27, 2014

Ophthalmologica 2014;232:136–143 DOI: 10.1159/000360909

Effect of Macular Ischemia on Intravitreal Ranibizumab Treatment for Diabetic Macular Edema Maria Douvali a Irini P. Chatziralli c Panagiotis G. Theodossiadis a Klio I. Chatzistefanou b Emmanouella Giannakaki a Alexandros A. Rouvas a  







2nd Department of Ophthalmology, Attikon Hospital, and b 1st Department of Ophthalmology, G. Gennimatas Hospital, University of Athens, Medical School of Athens, Athens, and c 2nd Department of Ophthalmology, Ophthalmiatreion Athinon Eye Hospital, Athens, Greece  



Abstract Purpose: To evaluate the impact of macular ischemia on the functional and anatomical outcome after intravitreal injections of ranibizumab for the treatment of diabetic macular edema (DME). Procedures: Participants were 49 patients with diabetes mellitus, divided into two groups based on the presence of ischemia on fluorescein angiography: (i) nonischemic group (n = 32) and (ii) ischemic group (n = 17). All patients were treated with intravitreal ranibizumab and were followed up for 6 months. The main outcome measures were changes in visual acuity (VA) and central foveal thickness (CFT). Results: There was a statistically significant improvement in VA and CFT between baseline and the end of the follow-up in the nonischemic group, while in the ischemic group there was no significant difference in VA but CFT differed significantly at the 6-month follow-up. Conclusions: Macular ischemia may have a negative impact on functional outcomes 6 months after intravitreal ranibizumab treatment in patients with DME but has no effect on anatomical outcomes. © 2014 S. Karger AG, Basel

© 2014 S. Karger AG, Basel 0030–3755/14/2323–0136$39.50/0 E-Mail [email protected] www.karger.com/oph


Diabetic macular edema (DME) is a significant cause of visual impairment in patients with diabetic retinopathy [1–3]. Its prevalence varies from 0 to 3% in patients with a recent diagnosis of diabetes and to 28% in patients with diabetes for more than 20 years [1–3]. Laser photocoagulation, either focal or grid, has been considered as the gold standard for the treatment of DME [4, 5]. The Early Treatment Diabetic Retinopathy Study (ETDRS) reported visual improvement or stabilization of vision over time in patients with clinically significant DME treated with laser in comparison with untreated patients [4, 5]. However, only 3% of eyes experienced significant visual acuity (VA) improvement of 3 or more ETDRS lines, consistent with recent studies as well [4–8]. Vascular endothelial growth factor (VEGF) has been found to play an important role in the pathogenesis of DME, as it has been associated with increased vascular permeability and breakdown of the blood-retina barrier, resulting in leakage of fluid and retinal thickening [6, 9–11]. There have been several studies showing improvement in VA as well as reduction in macular edema in patients treated with intravitreal anti-VEGF agents, especially bevacizumab, against DME [12–22]. Recent studies Alexandros A. Rouvas, MD, PhD 2nd Department of Ophthalmology, Attikon University Hospital 1, Rimini street, Haidari GR–12462 Athens (Greece) E-Mail alexander.rouvas @ gmail.com

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Key Words Ranibizumab · Diabetic macular edema · Treatment · Ischemia

Materials and Methods

most foveolar surfaces. Foveal thickness was measured manually in all scans using the caliper tool built into the OCT software by the same examiner, who was masked to the clinical, angiographic and functional status of the patients. Additionally, all patients underwent fluorescein angiography (FA) using Spectralis (Heidelberg Engineering, Heidelberg, Germany) at baseline and at the end of the follow-up. Baseline FA was assessed by 2 independent masked examiners, who grouped the patients into 2 categories: patients without ischemia (group 1, n = 32) and patients with ischemia (group 2, n = 17). Interobserver κ-statistical analysis was applied to the FA grouping. Macular ischemia was defined as (i) foveal avascular zone (FAZ) more than 1,000 μm and/or (ii) broken perifoveal capillary rings at the borders of the FAZ with distinct areas of capillary nonperfusion within 1 disk diameter of the foveal center in the transit phase of FA. The ischemic group also underwent FA every 3 months thereafter to evaluate the progression of macular ischemia. All patients received 0.05 ml intravitreal ranibizumab (Lucentis®, Novartis) at baseline and on a monthly basis for the next 2 months (for a total of 3 injections). As of month 3, injections were done according to pro re nata protocol to achieve stability. Specifically, retreatment was performed, if there was recurrence in macular edema, with CFT >250 μm (but improved from baseline >10%) and if VA presented an improvement of at least 0.1 logMAR (logarithm of the minimum angle of resolution) compared to baseline. All injections were performed under local anesthesia (0.5% proparacaine) and under standard sterile conditions. Topical antibiotics were administered to all patients 4 times a day for 5 days after the injection. Of note, laser was not used if retreatment was needed, so as to have similar groups, as well as not to induce more ischemia after laser treatment in the ischemic group. The main outcome measures were changes in VA and CFT measured by OCT. All variables were tested for normal distribution with the Kolmogorov-Smirnov test. For comparison of nominal variables between the two groups, the Student t test for independent samples or the Mann-Whitney-Wilcoxon test (MWW for brevity) was used as appropriate. Accordingly, for categorical variables, the χ2 test or Fisher’s exact test was performed. A p value of

Effect of macular ischemia on intravitreal ranibizumab treatment for diabetic macular edema.

To evaluate the impact of macular ischemia on the functional and anatomical outcome after intravitreal injections of ranibizumab for the treatment of ...
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