Exploratory analysis of the effect of intravitreal ranibizumab or triamcinolone on worsening of diabetic retinopathy in a randomized clinical trial

Abstract

Importance: The standard care for proliferative diabetic retinopathy (PDR) usually is panretinal photocoagulation, an inherently destructive treatment that can cause iatrogenic vision loss. Therefore, evaluating the effects of therapies for diabetic macular edema on development or worsening of PDR might lead to new therapies for PDR.

Objective: To evaluate the effects of intravitreal ranibizumab or triamcinolone acetonide, administered to treat diabetic macular edema, on worsening of diabetic retinopathy.

Design: Exploratory analysis was performed on worsening of retinopathy, defined as 1 or more of the following: (1) worsening from no PDR to PDR, (2) worsening of 2 or more severity levels on reading center assessment of fundus photographs in eyes without PDR at baseline, (3) having panretinal photocoagulation, (4) experiencing vitreous hemorrhage, or (5) undergoing vitrectomy for the treatment of PDR.

Setting: Community- and university-based ophthalmology practices.

Participants: Individuals with central-involved diabetic macular edema causing visual acuity impairment.

Interventions: Eyes were assigned randomly to sham with prompt focal/grid laser, 0.5 mg of intravitreal ranibizumab with prompt or deferred (≥24 weeks) laser, or 4 mg of intravitreal triamcinolone acetonide with prompt laser.

Main outcomes and measures: Three-year cumulative probabilities for retinopathy worsening.

Results: For eyes without PDR at baseline, the 3-year cumulative probabilities for retinopathy worsening (P value comparison with sham with prompt laser) were 23% using sham with prompt laser, 18% with ranibizumab with prompt laser (P = .25), 7% with ranibizumab with deferred laser (P = .001), and 37% with triamcinolone with prompt laser (P = .10). For eyes with PDR at baseline, the 3-year cumulative probabilities for retinopathy worsening were 40%, 21% (P = .05), 18% (P = .02), and 12% (P < .001), respectively. CONCLUSIONS AND RELEVANCE Intravitreal ranibizumab appears to be associated with a reduced risk of diabetic retinopathy worsening in eyes with or without PDR. Intravitreal triamcinolone also appears to be associated with a reduced risk of PDR worsening. These findings suggest that use of these drugs to prevent worsening of diabetic retinopathy may be feasible. Given the exploratory nature of these analyses, the risk of endophthalmitis following intravitreal injections, and the fact that intravitreal triamcinolone can cause cataract or glaucoma, use of these treatments to reduce the rates of worsening of retinopathy, with or without PDR, does not seem warranted at this time.

Figure 1

Cumulative probability of worsening of retinopathy among eyes without proliferative diabetic retinopathy at baseline by treatment group using life-table method. P value for comparison with sham+laser for ranibizumab+prompt laser, ranibizumab+deferred laser, and triamcinolone+prompt laser is 0.04, 0.04 and 0.04 at 1 year; 0.01, 0.005, and 0.64 at 2 years, and 0.25, 0.001, and 0.10 at 3 years. Each visit week includes visits that are ±14 days, except the 52, 68, 84, 120, 136-week visits that are ±8 weeks, and the 104, 156-week visits that are ±16 weeks.

Figure 2

Cumulative probability of worsening of retinopathy among eyes with proliferative diabetic retinopathy at baseline by treatment group using life-table method. P value for comparison with sham+laser for ranibizumab+prompt laser, ranibizumab+deferred laser, and triamcinolone+prompt laser throughout the 3 years of follow up is 0.05, 0.02, and <0.001 respectively. Each visit week includes visits that are ±14 days, except the 52, 68, 84, 120, 136-week visits that are ±8 weeks, and the 104, 156-week visits that are ±16 weeks.

Figure 3

Cumulative probability of worsening of retinopathy among study participants with two study eyes without proliferative diabetic retinopathy at baseline in both eyes by treatment group using life-table method.