Session Title: Vascular Diseases I
Session Date/Time: Friday 27/09/2013 | 08:00-10:00
Paper Time: 09:52
Venue: Hall C (Level 1)
First Author: P.Schlottmann ARGENTINA
Co Author(s): D. Chen J. Ehrlich
Diabetic retinopathy (DR) is the leading cause of new blindness in working-aged adults in industrialized countries. The Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale was developed to describe the progression of DR in a series of discrete steps. Progression (worsening) of ≥2 and ≥3 steps is associated with an increased long-term risk of vision loss. Secondary and exploratory analyses were conducted to analyze the effect of intravitreal ranibizumab on DR severity through 36 months in patients with diabetic macular edema (DME) enrolled in the RIDE and RISE clinical trials, and to identify prognostic factors for DR progression.
Retina specialty clinics in the USA and Latin America (65 principal investigators in each study)
Adults (≥18 years of age) with DME, best corrected visual acuity ranging from 20/40 to 20/320 (Snellen equivalent), and central subfield thickness of ≥275 μm (on time-domain optical coherence tomography) were eligible to enroll. Eligible participants were randomized 1:1:1 to receive monthly 0.3 mg ranibizumab, monthly 0.5 mg ranibizumab, or monthly sham injections. Participants in the sham injection group were eligible for crossover to 0.5 mg ranibizumab during the third year. All participants were eligible for macular laser beginning at month 3, and panretinal photocoagulation (PRP) was available as needed. Clinical examinations were performed monthly, with fundus photographs (taken at baseline and pre-specified intervals) graded by a central reading center. Analysis outcomes included ≥2 or ≥3-step change on the ETDRS DR severity scale, and a composite outcome evaluating clinical progression based on fundoscopic changes and clinically-important events (e.g. occurrence of vitreous hemorrhage, need for vitrectomy or PRP, neovascularization with adverse events, or progression from nonproliferative to proliferative DR). Time to first DR progression was analyzed by Kaplan-Meier methods to calculate cumulative probabilities by treatment group. Cox regression identified baseline characteristics significantly associated with DR progression in single covariate analysis, which were subsequently included in multiple covariate analysis.
Data from 759 participants was analyzed. At month 36 a greater proportion of eyes in the ranibizumab arms had a ≥2- or ≥3-step DR regression (improvement) on the ETDRS severity scale compared to eyes in the sham/0.5 mg crossover group. A ≥3-step improvement was achieved at 36 months by 3.3%, 15.0% and 13.2% of the sham/0.5 mg crossover, 0.3 mg and 0.5 mg ranibizumab treated eyes, respectively. Through 36 months 33.9% of eyes originally randomized to sham developed proliferative DR (PDR) as measured by the composite outcome, compared to 12.8% and 15.1 % of 0.3 mg and 0.5 mg ranibizumab-treated eyes respectively. Through 24 months DR progression in ranibizumab treated eyes was significantly related to presence of baseline macular capillary loss (p=0.005), but not to other baseline characteristics including DR severity, visual acuity, central subfield thickness, retinal volume, renal disease, or glycemic control. In the sham-treated group more severe baseline DR (p<0.0001) and presence of subretinal fluid (p=0.04) were associated with DR worsening. In the total cohort, ranibizumab treatment was the most significant factor in reducing risk for DR progression (p<0.0001 both doses). Analysis of the 36 month data is underway and will be reported.
This analysis of patients with DME who participated in the RISE and RIDE phase III trials demonstrates that ranibizumab reduces DR severity in many patients, and can slow the clinical progression of DR. These data underscore the need for early screening and appropriate intervention in DME patients, who without treatment are at high risk of developing PDR. Future management of patients with DME may be informed by further evaluation of baseline characteristics as prognostic factors’ of anatomic outcomes associated with anti-VEGF therapy.