Intravitreal Ranibizumab Therapy for Diabetic Macular Edema in Routine Practice: Two-Year Real-Life Data from a Non-interventional, Multicenter Study in Germany

IntroductionThe prospective, non-interventional OCEAN study examined the use of intravitreal ranibizumab injections for the treatment of diabetic macular oedema (DME) in a real-world setting in Germany.MethodsAdults with DME receiving 1ranibizumab (0.5mg) injections were recruited by 250ophthalmologists. Best-corrected visual acuity (VA) testing, imaging and treatments were performed according to the investigators' routine practice and documented over 24months.ResultsThe full analysis set included 1226 participants. Mean baseline VA was 60.6 [95% CI: 59.7; 61.5] Early Treatment Diabetic Retinopathy Study letters. VA improved by 15letters in 21.5% and 23.5% of the participants at 12months and 24months, respectively. They received a mean number of 4.42 [95% CI: 4.30; 4.54] injections in the first year and 5.52 [95% CI: 5.32; 5.73] injections over 24months, which was markedly lower than in clinical trials. Only 33.4% of the participants received an upload with four initial monthly injections as recommended by the German ophthalmologic societies. Time-to-event analyses that account for missing data inherent to a non-interventional study design demonstrated that participants receiving 7injections in the first year had a faster response, but the duration of the response was shorter compared to the subgroups receiving 1-3 and 4-6injections. Serious adverse events were reported for 143/1250 (11.4%) participants in the safety population.ConclusionUnder-treatment is a major problem of DME anti- vascular endothelial growth factor therapy under real life conditions. Despite fewer injections given compared to randomised controlled trials with a consequently reduced overall mean visual gain, a profound functional improvement (15letters) was achieved over 2years in 23.5% of eyes with DME.Trial Registration NumberNCT02194803, ClinicalTrials.gov.FundingNovartis Pharma GmbH, Nuremberg, Germany

GA lesion growth rates for each individual in the combined study.

<p>The measured area of GA was square-root transformed. From the transformed area the growth rate was calculated per year in [mm/year]. Growth rates from each individual were then obtained by calculating the mean of all growth rates of the individual. If both eyes were affected, the mean of both eyes were calculated resulting in a single growth variable per individual. These individual growth rates were further transformed by the natural logarithm (ln) and were stratified either by (A) the genotype at ARMS2_rs10490924 or (B) the genotype at C3_rs2230199 or (C) the presence or absence of bilateral GA.</p

Multivariate linear regression analysis of factors significantly correlated to GA growth.

<p>^a P value of linear regression model vs. null model</p><p>^b combined effect sizes were estimated from random effects model (meta-analysis).</p><p>Multivariate linear regression analysis of factors significantly correlated to GA growth.</p

Summary characteristics of participating study populations.

<p>FAF = fundus autofluorescence.</p><p>Summary characteristics of participating study populations.</p

Forestplot representations of univariate linear regression models.

<p>Univariate linear regression models were fitted for variables ARMS2_rs10490924, C3_rs2230199 and bilateral GA for each study separately. Slope and standard errors obtained from the models of each study were combined by performing a meta-analysis assuming a random effects model. The combined estimates for slope and 95% confidence intervals (CI) were computed from the random effects model. In all analyses, no evidence was found for heterogeneity (P_{heterogeneity} > 0.05).</p