Analysis weighs benefits of anti-VEGF therapy in proliferative diabetic retinopathy

May 06, 2009

Off-label treatment with intravitreal bevacizumab (Avastin, Genentech) resulted in regression of retinal neovascularization in patients with proliferative diabetic retinopathy (PDR) in a retrospective analysis performed by the Pan-American Collaborative Retina Study Group (PACORES). The benefits of bevacizumab therapy, however, decreased from the 6-month follow-up to 24 months, a development being studied further, said J. Fernando Arevalo, MD, FACS, director of ophthalmology at the Clinica Oftalmologica Centro Caracas in Caracas, Venezuela.

Fort Lauderdale, FL-Off-label treatment with intravitreal bevacizumab (Avastin, Genentech) resulted in regression of retinal neovascularization in patients with proliferative diabetic retinopathy (PDR) in a retrospective analysis performed by the Pan-American Collaborative Retina Study Group (PACORES). The benefits of bevacizumab therapy, however, decreased from the 6-month follow-up to 24 months, a development being studied further, said J. Fernando Arevalo, MD, FACS, director of ophthalmology at the Clinica Oftalmologica Centro Caracas in Caracas, Venezuela.

Investigators reviewed the records of 39 patients (43 eyes) with high-risk PDR who were treated with at least one injection of 1.25 mg (51%) or 2.5 mg (49%) intravitreal bevacizumab. Twenty-eight percent of the patients were insulin-dependent diabetics. In addition, 72% had undergone pan-retinal photocoagulation (PRP) at least 6 months before injection of bevacizumab.

The mean baseline best-corrected visual acuity (BCVA) was 0.94 LogMAR; at 24 months, the mean BCVA was 0.67 LogMAR, a difference that was statistically significant. By subgroups, 81% of eyes remained stable, while 5 eyes (11%) improved two or more ETDRS lines of BCVA. In addition, Dr. Arevalo reported a statistically significant improvement in central macular thickness measured by optical coherence tomography.

At 6 months, 60% of eyes had a total regression of retinal neovascularization and 34% had a partial regression. However, 24-month results indicated that only 39% of patients had a total regression while 35% had partial regression and 25% had no regression.

The mean number of intravitreal injections per eye was 4 with a mean interval of 14 weeks.

Since there was no significant difference in results between the two dosage groups, Dr. Arevalo suggested that the lower dose would be preferable. He also commented on the tendency toward a decrease in the response to intravitreal bevacizumab over time.

“With 60% of eyes in our cohort at 24 months requiring additional PRP or vitrectomy, we raised the question of tachyphylaxis with intravitreal bevacizumab in these cases. We are performing analysis for that study currently,’ Dr. Arevalo said.

He also described a related retrospective study on the development or progression of tractional retinal detachment (TRD) following preoperative intravitreal bevacizumab in severe PDR cases. Investigators identified 25 eyes (25 patients) that had developed TRD or experienced progression from a series of 698 eyes that had received bevacizumab injections. All patients had a PRP at least 2 months before the injections, and all eyes had PDR that was refractory to PRP. In addition, all patients had uncontrolled diabetes.

Seventy-three percent of patients received an injection of 1.25 mg of bevacizumab and 25% had received the 2.5 mg dose. According to Dr. Arevalo, 25 eyes of the 698 who had received treatment developed or had progression of TRD, an incidence of 3.2%. The mean time from injection to TRD was 11 days. Investigators found a 3% rate of TRD in patients who had received the 1.25 mg dose of bevacizumab compared with an 8.3% rate among those who received the higher dose.

Among patients who developed TRD, the mean baseline BCVA was 0.8 LogMAR; this dropped to 2.2 after development of TRD then improved following vitrectomy to 0.9 LogMAR. All differences were statistically significant.

Visual acuity improved significantly in all patients who underwent vitrectomy, but when investigators compared baseline BCVA with that after vitrectomy, they found that 50% of eyes improved, 25% remained stable, and 25% lost two or more lines of BCVA.Dr. Arevalo hypothesized that the development or progression of TRD was the result of rapid neovascular involution with accelerated fibrosis and posterior hyaloid contraction as a response to decreased levels of vascular endothelial growth factor. He suggested that in cases of high risk to progression to TDR that might involve the central macular region, the time to surgery should be anticipated.

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