Treatment Order with Panretinal Photocoagulation Influences PDR Outcomes

Ehsan Rahimy, MD

Credit: Stanford University

Initial therapy with panretinal photocoagulation (PRP), followed by anti-vascular endothelial growth factor (VEGF) injections, was linked to an increased need for pars plana vitrectomy (PPV) in patients with proliferative diabetic retinopathy (PDR) compared with anti-VEGF therapy first.¹

This retrospective cohort study, collecting data from January 2003 to January 2024, revealed the PRP-first treatment order also led to a greater risk of vitreous hemorrhage and tractional retinal detachment (TDR), compared with an anti-VEGF-first cohort.

“In this study, administration of PRP first was associated with an increased risk of undergoing PPV, as well as developing vitreous hemorrhage and TDR, compared with anti-VEGF injection first in a large, heterogeneous, real-world database of matched patients with PDR,” wrote the investigative team, led by Ehsan Rahimy, MD, Horngren Family Vitreoretinal Center, Byers Eye Institute, Department of Ophthalmology, Stanford University School of Medicine.

Combination anti-VEGF and PRP therapy is commonly used for PDR treatment among ophthalmologists in real-world settings despite not being studied in randomized clinical trials.² Observational studies have searched for optimal timing and treatment order with anti-VEGF and PRP, but there are limited data on how these choices affect PDR outcomes.³

Thus, a consensus has not been made on the order of treatment with the combination of PRP and anti-VEGF injections for PDR, with or without diabetic macular edema (DME).

In this study, Rahimy and colleagues evaluated the outcomes of patients with PDR treated with PRP and subsequent anti-VEGF therapy, with matched patients treated with anti-VEGF therapy and subsequent PRP.¹ Data were collected in the TriNetX aggregated electronic health records network during the study period, with the analysis occurring in January 2024.

Patients with new PDR diagnoses were stratified by therapy with PRP and subsequent anti-VEGF injection (Cohort 1) or anti-VEGF injection and subsequent PRP (Cohort 2). The primary outcome was the need for PPV, defined by Current Procedural Terminology (CPT) codes 67040 or 67113), and secondary outcomes included the incidence of vitreous hemorrhage or TRD.

Before propensity score matching (PSM), controlling for baseline demographic characteristics and medical comorbidities, 2167 patients with PDR were included in Cohort 1 and 1549 were included in Cohort 2. After PSM, 1377 patients were assessed in each cohort – 641 (46.6%) and 663 (48.1%) in each cohort were female, respectively, and the mean age was 63.0 years.

Upon analysis, treatment in Cohort 1 was linked to increased rates of PPV at 5 years compared with patients treated with anti-VEGF injection and subsequent PRP (relative risk [RR], 1.88; 95% CI, 1.55–2.27; risk difference, 8.93%; 95% CI, 6.31–11.55; P <.001). Similar rates were identified at 6 months, 1 year, and 3 years, according to Rahimy and colleagues.

Furthermore, treatment with PRP and subsequent anti-VEGF injection, in Cohort 1, was correlated with increased vitreous hemorrhage (RR, 1.40; 95% CI, 1.09–1.80; RD, 6.47%; 95% CI, 1.66–11.29; P <.001) and TRD (RR, 1.85; 95% CI, 1.35–2.53; RD, 4.31%; 95% CI, 2.10–6.52; P <.001) at 5 years.

Again, Rahimy and colleagues identified similar findings at 6 months, 1 year, and 3 years, compared with those treated with anti-VEGF injection and subsequent PRP in Cohort 2. The team indicated a related analysis using the same database showed similar results as these findings.⁴

“Related analysis evaluating cohorts of patients with PDR treated with PRP monotherapy vs anti-VEGF monotherapy using the same real-world database suggests a similar direction of results,” they wrote.¹ “...Further studies are needed to determine the optimal order, if any, for treatment of patients presenting with PDR.”

References

1. _{Alsoudi AF, Wai KM, Koo E, Parikh R, Mruthyunjaya P, Rahimy E. Initial Therapy of Panretinal Photocoagulation vs Anti-VEGF Injection for Proliferative Diabetic Retinopathy. JAMA Ophthalmol. Published online August 29, 2024. doi:10.1001/jamaophthalmol.2024.3283}
2. _{Writing Committee for the Diabetic Retinopathy Clinical Research Network. Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. JAMA. 2015;314(20):2137–2146. doi:10.1001/jama.2015.15217}
3. _{Zhang, W., Zhao, G., Fan, W. et al. Panretinal photocoagulation after or prior to intravitreal conbercept injection for diabetic macular edema: a retrospective study. BMC Ophthalmol 21, 160 (2021). https://doi.org/10.1186/s12886-021-01920-8}
4. _{Alsoudi AF, Wai KM, Koo E, Parikh R, Mruthyunjaya P, Rahimy E. Progression to Pars Plana Vitrectomy in Patients With Proliferative Diabetic Retinopathy. JAMA Ophthalmol. 2024;142(7):662–668. doi:10.1001/jamaophthalmol.2024.1844}