Lessons on Proliferative Diabetic Retinopathy from the Diabetic Retinopathy Clinical Research Network

Educational Objectives

The goal of this lecture is to improve diagnosis and treatment of diabetic retinopathy. After hearing and assimilating this program, the clinician will be better able to:

1. Describe safety outcomes in the Protocol S study conducted by the Diabetic Retinopathy Clinical Research Network.

Summary

Proliferative diabetic retinopathy (PDR): panretinal photocoagulation (PRP) standard of care for treatment of PDR; in DRS study, PRP reduced 2-yr risk for severe vision loss by 60%; in ETDRS, risk for visual loss 1% when both eyes considered; eyes at highest risk include those with preretinal hemorrhage and severe neovascularization (NV) or new vessels on disc; limitations of PRP include ≈18% rate of diabetic macular edema (DME), loss of night and side vision, loss of accommodation, and low risk for angle closure or choroidal effusion; dramatic improvements seen in retinopathy scores after 2 yr of monthly treatment with ranibizumab; 2-step improvement in severity seen in eyes treated with ­anti–vascular endothelial growth factor (anti-VEGF) vs sham treatment

Protocol F: small study sought to determine whether DME developed in unaffected eyes after PRP, and to examine effect of delivering PRP in 1 vs 4 sittings; number of sittings not randomized; for patients treated in 4 sittings, burns performed 4 wk apart; majority of patients had milder disease (some did not have PDR); 1-sitting group required additional PRP; final central subfield thickness and visual acuity (VA) similar between groups

Protocol S: same proportion of patients in each group had DME; study designed to show whether ranibizumab noninferior to PRP (based on 5-letter difference in VA) in patients with PDR; secondary outcomes level of vision throughout study, peripheral vision, presence of DME, and need for vitrectomy; during year 1, PRP group seen every 16 wk, but ranibizumab group treated every 4 wk; during year 2, visit schedule could be extended in ranibizumab group

Methodology: initially, 4 to 6 injections of ranibizumab given, depending on presence of NV; beginning at 6 mo, drug given if eye improved, but withheld if eye stable; injections resumed if NV worsened; PRP given in 1 to 3 sittings within 8-wk period; additional ranibizumab allowed if NV increasing; study included 200 patients per arm, 20% of whom had DME at baseline

Results: patients in Protocol S had more severe disease than those in Protocol F; almost half of PRP group needed additional PRP during study (median time to complete therapy 7 mo); in ranibizumab group, during first year, ≈7 treatments required in patients without DME (9 treatments required in those with DME); at 2 yr, mean VA slightly better in ranibizumab group; ranibizumab group achieved better VA sooner; peripheral vision worse in PRP group, but this finding associated with only minor differences in quality of life; half of patients had 2-step improvement in PDR

Vitrectomy: only positive benefit in ranibizumab group fewer vitrectomies; similar numbers of patients in each group had vitreous hemorrhage and retinal detachment

Management of PDR: good results observed with PRP and anti-VEGF treatment; indirect PRP also may be effective; recommendations — management depends on whether patient has DME; for patients with DME who can attend multiple visits, PRP may be deferred until DME treated and used only if NV returns; in patients without DME, speaker favors PRP; advantages of PRP — may be completed in 1 or 2 visits; effect long lasting; PRP less costly than ranibizumab, and risk for infection low; ranibizumab associated with better VA outcomes, fewer vitrectomies, and decreased risk of developing DME

Protocol J: demonstrated increased risk for vitreous hemorrhage in patients treated with laser instead of ranibizumab; rates of vitrectomy and retinal detachment same in both groups; these findings consistent at 14 and 56 wk

Protocol N: compared ranibizumab with saline in patients with vitreous hemorrhage; no increase in frequency of retinal detachment observed in ranibizumab group

Selecting treatment for PDR: treatment that produces regression of NV may lead to progressive traction; traction may occur more quickly in patients treated with anti-VEGF therapies, but also possible after PRP; patients with severe NV should be monitored closely

Readings

Bhavsar AR et al: Evaluation of results 1 year following short-term use of ranibizumab for vitreous hemorrhage due to proliferative diabetic retinopathy. JAMA Ophthalmol 2014 Jul;132(7):889-90; Diabetic Retinopathy Clinical Research Network: Observational study of the development of diabetic macular edema following panretinal (scatter) photocoagulation given in 1 or 4 sittings. Arch Ophthalmol 2009 Feb;127(2):132-40; Diabetic Retinopathy Clinical Research Network: Randomized trial evaluating short-term effects of intravitreal ranibizumab or triamcinolone acetonide on macular edema after focal/grid laser for diabetic macular edema in eyes also receiving panretinal photocoagulation. Retina 2011 Jun;31(6):1009-27; Early Treatment Diabetic Retinopathy Study Research Group: Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Ophthalmology 1991 May;98(5 Suppl):766-85; No authors listed: Photocoagulation treatment of proliferative diabetic retinopathy: the second report of diabetic retinopathy study findings. Ophthalmology 1978 Jan;85(1):82-106; Writing Committee for the Diabetic Retinopathy Clinical Research Network, et al: Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized clinical trial. JAMA 2015 Nov 24;314(20):2137-46.

Disclosures

For this program, the following has been disclosed: Dr. Wenick reported nothing relevant to disclose. The planning committee reported nothing to disclose. 

Acknowledgements

Dr. Wenick was recorded at What’s New in Diabetic Retinopathy and Venous Occlusive Disease, presented by the Wilmer Eye Institute at Johns Hopkins University School of Medicine and the Department of Ophthalmology and held November 4, 2016, in Baltimore, MD. For information about upcoming CME courses presented by the Wilmer Eye Institute, visit www.wilmer.jhu.edu. The Audio Digest Foundation thanks the speakers and the Wilmer Eye Institute at Johns Hopkins University School of Medicine and the Department of Ophthalmology for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

OP551103

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.