In a double-blind phase 3 trial, a combination therapy intravitreally applied during pars plana vitrectomy for rhegmatogenous retinal detachment (RRD) did not affect the rate of proliferative vitreoretinopathy (PVR) any differently than a placebo, according to a report published in Ophthalmology. Investigators reviewed the use of 200 mg/ml 5-fluorouracil (5-FU) and 5 IU/ml of a low molecular weight heparin (dalteparin) in conjunction with PPV.
The interventional Prophylactic Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy in High-risk Patients with Retinal Detachment trial (PRIVENT, Clinicaltrials.gov ID: NCT02834559) considered 325 patients who underwent PPV for primary RRD at 13 clinical centers in Germany from October 2016 to March 2020. The researchers assessed patients’ PVR risk using laser flare photometry.
All participants presented laser flare of at least 15.0 photon counts per millisecond. The combined 5-FU and dalteparin was delivered intravitreally during surgery to 163 patients, while another 162 individuals were given a balanced salt solution placebo. Final follow-ups occurred 12 weeks after surgery. Participants’ mean age was 65±10 years, 65% were pseudophakic, and 68% had detachment affecting the macula.
An interim included 280 patients, 215 of whom exhibited no PVR-grade (retinal folds or subretinal strands in clock hours) posterior to the equator (CP). Of the remainder, 13 in each cohort displayed a PVR grade of CP1 or higher, and 39 were considered “not assessable,” 23 who received the drug combination, and 16 received the placebo. Sensitivity analysis demonstrated comparable PVR rate between groups (P =.54).
In the final analysis, the case and control sets showed similar “PVR rate (primary analysis, modified intention-to-treat: Verum: 28% vs Placebo: 23% (including not assessable cases as failure); Odds ratio (OR) 1.25 (95% confidence interval (CI) 0.76 to 2.08), P =.77; per-protocol: 12% vs 12%, OR 1.05 (0.47 to 2.33), P =.47).” There were also no significant differences between groups in secondary endpoints: re-surgeries, PVR grade CA, and BCVA, and no safety concerns arose. Mean laser flare was 31±26 pc/ms, which may represent normal inflammation caused by retinal detachment. The success rate was 83% to 87%, in line with published data in routine RRD surgeries.
Researchers speculate the similar PVR rates were mainly due to laser flare photometry’s insufficiency at selecting high-risk individuals. Prior studies have suggested factors such as aphakia, ocular trauma, and concurrent uveitis may predict risk, but their prognostic benefit is still unknown.
Multiple centers with various flare-measuring instrument models was a limitation of this study, as were non-assessable cases from missing final visit fundus images.
““Failure and PVR rates were comparable between both arms. One could conclude that elevated laser flare values as obtained in our cohort, did not select the high-risk patients,” the researchers report.
The unexpected finding that laser flare photometry may not accurately detect high risk for PVR can be considered a key outcome of this trial.
Schaub F, Schiller P, Hoerster R, et al. Intravitreal 5-fluorouracil and heparin to prevent proliferative vitreoretinopathy: results from a randomized clinical trial. Ophthalmol. Published online June 6, 2022. doi: 10.1016/j.ophtha.2022.05.024