Insights on preventing TRD in PDR patients after Avastin, vitrectomy

Reviewed by J. Fernando Arevalo, MD

Study results provide new information about the risk and strategies for preventing tractional retinal detachment (TRD) development or progression in eyes with severe proliferative diabetic retinopathy (PDR) receiving intravitreal bevacizumab (Avastin, Genentech) prior to vitrectomy.

Conducted as a larger follow-on to a previously published, retrospective study that included 211 intravitreal bevacizumab injections [Arevalo JF, et al. Br J Ophthalmol. 2008;92(2):213-216], the current retrospective, multicenter study reviewed 698 cases and found TRD developed or progressed in 25 eyes (25 patients, 3.2%).

Advanced proliferative diabetic retinopathy. A) Color photograph. B) Fluorescein angiogram demonstrating neovascularization (NVD and NVE). C-D) Three weeks after intravitreal bevacizumab (1.25 mg), the patient developed tractional retinal detachment temporal to the foveal with areas of lack of perfusion (D). Note that the areas of hyperfluorescence corresponding to NVE and NVE had regressed (D). (Images courtesy of J. Fernando Arevalo, MD)

All 25 patients had PDR refractory to panretinal photocoagulation (PRP) and uncontrolled diabetes mellitus associated with an elevated HBA1c. Although the average time to onset or progression of TRD was 13 days (range 3 to 31), it occurred within 5 days after the bevacizumab injection in 82% of the 25 eyes.

Twenty-five percent of eyes had a ≥2-line loss from their baseline best corrected visual acuity (BCVA) after vitrectomy, reported J. Fernando Arevalo, MD, the Edmund F. and Virginia B. Ball Professor of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore. He is also chairman, Department of Ophthalmology, Johns Hopkins Bayview Medical Center.

“Adjuvant use of bevacizumab in eyes undergoing vitrectomy for PDR has many advantages,” Dr. Arevalo explained. “By reducing the risk of intraoperative bleeding, it may facilitate the removal of fibrovascular membranes and provide better visibility that reduces the likelihood of creating an iatrogenic retinal break. In addition, chances of postoperative complications, such as rebleeding or fibrinoid syndrome, may be reduced.”

TRD may occur

Dr. Arevalo pointed out that TRD may also occur or progress after intravitreal bevacizumab in these cases, particularly in patients whose diabetes is uncontrolled and when there is a long interval between intravitreal bevacizumab injection and vitrectomy.

“Therefore, we recommend that surgeons should plan for timely vitrectomy in eyes at risk, within four days after the intravitreal injection, and particularly when progression of existing TRD might involve the central macular region,” he added.

In the earlier report on TRD following intravitreal bevacizumab in eyes with severe PDR, Dr. Arevalo, with colleagues in the Pan-American Collaborative Retina Study (PACORES) Group and investigators from centers in the United States, reported TRD developed or progressed in 11 eyes (patients) out of the 211 injections (5.2%).

The present study was conducted by members of the PACORES Group. The 25 patients who had development or worsening of TRD had a mean age of 39.5 years and just over half were men.

Lower dose prudent

All had undergone PRP at least 2 months before the bevacizumab injection. Eighteen of the 25 patients had type 1 diabetes mellitus. Mean HbA1c for the group was 9.2%.

The intravitreal dose of bevacizumab was 1.25 mg in all cases.

“It has been reported that diabetic eyes may be very sensitive to intravitreal bevacizumab [Avery R, et al. Ophthalmology. 2006;113(10):1695.e1-15],” Dr. Arevalo said. “Use of a lower dose may be prudent in eyes with pre-existing significant traction.”

TRD onset or progression led to significant worsening of mean BCVA with a drop from LogMAR 0.8 (20/120) at baseline to 2.2 (count fingers). Final mean BCVA after vitrectomy was LogMAR 0.9 (20/160).

“Twenty eyes underwent vitrectomy, and all 20 gained 2 or more lines of BCVA after the surgery compared with BCVA after development or worsening of TRD,” Dr. Arevalo said. “Compared with their baseline before intravitreal bevacizumab, however, only 10 eyes (50%) had improved BCVA, whereas BCVA was stable in 5 (25%) eyes, and 5 (25%) lost 2 or more lines of vision.”

Causal link

Both the temporal association and biologic plausibility support a cause-and-effect relationship between intravitreal bevacizumab and the development or progression of TRD, Dr. Arevalo said.

“The short average time between the injection and the TRD event in our series suggests a cause-and-effect relationship,” Dr. Arevalo explained. “Although TRD development or progression could have happened by natural history, rapid involution of neovascularization in response to decreased VEGF levels following bevacizumab injection may accelerate fibrosis and posterior hyaloidal contraction.”

J. Fernando Arevalo, MD

E: arevalojf@jhmi.edu

This article is based on a presentation given by Dr. Arevalo at the 2017 Retina World Congress.  He has no relevant financial interests to disclose.