Elsevier

Ophthalmology

Volume 122, Issue 7, July 2015, Pages 1395-1401
Ophthalmology

Original article
Predictors of Functional and Anatomic Outcomes in Patients with Diabetic Macular Edema Treated with Ranibizumab

Presented in part at: Association for Research in Vision and Ophthalmology Annual Meeting, May 2014, Orlando, Florida.
https://doi.org/10.1016/j.ophtha.2015.02.036Get rights and content
Under a Creative Commons license
open access

Objective

To investigate baseline predictors of month 24 best-corrected visual acuity (BCVA) and central foveal thickness (CFT) in patients with diabetic macular edema (DME) treated monthly with ranibizumab or sham.

Design

Post hoc analysis of DME patients in 2 identical phase 3 studies.

Participants

Patients randomized to ranibizumab (n = 502) or sham (n = 257).

Methods

Multivariate regression on predictors with P < 0.20 in univariate logistic regression using backward selection to retain predictors with P < 0.05.

Main Outcome Measures

Patient characteristics correlating with month 24 BCVA in Early Treatment Diabetic Retinopathy Study letter score ≥70 (20/40) or ≤50 (20/100), gain or loss from baseline BCVA of ≥15, or CFT ≤250 μm.

Results

Baseline predictors of BCVA ≥20/40 in ranibizumab-treated patients were good BCVA, submacular fluid, no cardiovascular disease, no scatter photocoagulation, and male gender, whereas in sham-treated patients, they were mild increase in CFT, presence of hard exudates in center subfield, and absence of renal disease. Predictors of improvement in BCVA letter score ≥15 in ranibizumab-treated patients were poor BCVA, submacular fluid, young age, and short diabetes duration, and those in sham-treated patients were poor BCVA, young age, and mild increase in CFT. Predictors of resolution of edema (CFT ≤250 μm) in ranibizumab-treated patients were mild foveal thickening and prominent subfoveal fluid, and those in sham-treated patients were poor BCVA, mild foveal thickening, and statin usage. Month 24 BCVA ≤20/100 was predicted by poor baseline BCVA in ranibizumab-treated patients, and by poor baseline BCVA, large intraretinal cystoid spaces, renal disease, and absence of hypercholesterolemia in sham-treated patients. Loss of BCVA ≥15 letters was predicted in sham-treated patients by submacular fluid, intraretinal cystoid spaces, and renal disease.

Conclusions

Patients with DME and submacular fluid, intraretinal cysts, severe thickening, or renal disease respond poorly when untreated and respond well to ranibizumab treatment. Elimination of submacular fluid, intraretinal cysts, and severe thickening are important goals of DME treatment, and in patients with renal disease, treatment should be very aggressive, with a goal of eliminating all macular fluid.

Abbreviations and Acronyms

BCVA
best-corrected visual acuity
CFT
central foveal thickness
CST
central subfield thickness
DME
diabetic macular edema
ETDRS
Early Treatment Diabetic Retinopathy Study
OCT
optical coherence tomography
OR
odds ratio
PRP
panretinal photocoagulation
VEGF
vascular endothelial growth factor

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Supplemental material is available at www.aaojournal.org.

Financial Disclosure(s): The author(s) have made the following disclosure(s): N.L.: Employee – Genentech, Inc, (South San Francisco, CA).

P.A.C.: Consultant (institutional remuneration) – Genentech, Inc, (South San Francisco, CA); Regeneron Pharmaceuticals, Inc., (Tarrytown, NY) Aerpio (Cincinnati, OH); Consultant (personal remuneration) – Abbvie; Advanced Cell Technology (DSMC); Aerpio; Allergan (Irvine, CA); Alimera (Atlanta, GA); Applied Genetic Technologies Corporation (Gainesville, FL); Eleven (Cambridge, MA); Genentech, Inc, (South San Francisco, CA); Kala (Cambridge, MA); Regeneron Pharmaceuticals, Inc; Financial support – Genentech, Inc, (South San Francisco, CA); Regeneron Pharmaceuticals, Inc; Aerpio; Allergan; Genzyme (Cambridge, MA); Molecular Partners (Zurich, Switzerland); Oxford BioMedica (Oxford, UK); Roche (Basil, Switzerland); Equity owner – Graybug (Baltimore, MD).

Supported in part by an Association for Research in Vision and Ophthalmology (ARVO) National Eye Institute Travel Grant for presentation at ARVO 2014 (R.S.); the George S. and Dolores Doré Eccles Professorship of Ophthalmology and Neuroscience, Baltimore, MD. (P.A.C.). Genentech, Inc., participated in the design and conduct of the study and in data collection, management, analysis, and interpretation. Assistance in preparation of the figures was provided by Grace H. Lee, PharmD, and Michael P. Bennett, PhD, of Envision Scientific Solutions (Southport, CT), and funded by Genentech, Inc., (South San Francisco, CA).

Author Contributions:

Conception and design: Sophie, Lu, Campochiaro

Analysis and interpretation: Sophie, Lu, Campochiaro

Data collection: Sophie, Lu, Campochiaro

Obtained funding: Sophie, Lu, Campochiaro

Overall responsibility: Sophie, Lu, Campochiaro