5-Fluorouracil or Heparin fail to prevent proliferative vitreoretinopathy in patients with RRD
GERMANY: A recent report in journal, Ophthalmology found that intravitreal 5-Fluorouracil (5-FU) and heparin did not seem to lower the occurrence of proliferative vitreoretinopathy (PVR) in eyes with primary rhegmatogenous retinal detachment (RRD).
The key factor in postoperative failure and retinal redetachment following primary rhegmatogenous retinal detachment is proliferative vitreoretinopathy. With the exception of surgical intervention in the incidence of a retinal redetachment, there is currently no standard therapy available to prevent or treat PVR. In high-risk eyes, 5-fluorouracil (5-FU) and low-molecular weight heparin (LMWH) have shown promising results in prior studies.
This study's goal was to evaluate the incidence of PVR in high-risk individuals with primary RRD to that of patients who received a placebo and adjuvant intravitreal therapy with 5-FU and LMWH.
A randomised, double-blind, controlled, multicenter, interventional trial was carried out to achieve this goal. Included were patients with RRD who were thought to be at high risk for PVR. By using laser flare photometry to quantify aqueous flares without being invasive, the risk of PVR was evaluated. During a routine pars plana vitrectomy, patients were randomly assigned in 1:1 ratio to receive either verum (200 mg/ml 5-FU and 5 IU/ml dalteparin) or a placebo (balanced salt solution). A total of 325 individuals were assigned among 13 German trial sites (verum, 163; placebo, 162). The primary end point was the appearance of PVR grade CP 1 or higher within 12 weeks of surgery (full-thickness retinal folds or subretinal strands in clock hours positioned posterior to equator). Fundus photos were evaluated by an end point committee for grading. Redetachment rate and best-corrected visual acuity were secondary end objectives. Utilizing the O'Brien and Fleming boundaries, a group sequential design with a single interim analysis was used. Using a Mantel-Haenszel test stratified by surgeon, the incidence of proliferative vitreoretinopathy grade CP was compared.
Key findings of the study:
- The average laser flare in the research eyes was 31 ± 26 pc/ms.
- There was no discernible difference in PVR rate.
- Verum 28% vs. placebo 23% (counting non-assessable cases as failures); odds ratio [OR], 1.25; 95% confidence interval [CI], 0.76-2.08; P = 0.77; were the results of the primary analysis in the modified intention-to-treat population.
- Those in the group who followed the protocol were as follows: 12% vs. 12%; OR, 1.05; 95% CI, 0.47-2.34; P = 0.47
- No secondary endpoint revealed a meaningful distinction between treatment groups.
- No significant safety hazards were found to exist during the study period.
The researchers concluded, "Overall, we could not show a difference in incidence of PVR between therapy with intraoperative intravitreal 5-FU and LMWH and placebo treatment."
Reference
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
