Combination Therapy for Diabetic Retinopathy Reduces DME Risk

A recent retrospective analysis examining the effects of combining anti-vascular endothelial growth factor (anti-VEGF) treatments with panretinal photocoagulation (PRP) has indicated a reduced risk of diabetic macular edema (DME).1

PRP has become a mainstay in the treatment of retinal ischemic disease, particularly proliferative diabetic retinopathy (PDR). Despite its effectiveness, there have been concerns regarding the adverse effects of PRP treatment. The most common side effects include choroidal effusions, exudative retinal detachments, visual field deficits, night vision defects, and macular edema.2

Anti-VEGF also exhibits positive effects on treating PDR and reducing leakage in DME. Anti-VEGF therapies have also been proposed as a treatment for PDR; compared to those receiving PRP alone, anti-VEGF monotherapy recipients had lower rates of DME and less visual field loss.1

“This design emphasizes the potential for varying treatment responses but does not reflect real-world scenarios where patients might receive diverse treatment modalities and continue clinical follow-up regardless of complications,” wrote Hsuan-Chieh Lin, MD, National Taiwan University, and colleagues. “Therefore, it is important to evaluate the efficacy of combining anti-VEGF agents and PRP alone for patients with PDR on the risk of DME or vitreous hemorrhage (VH) and relevant clinical ocular outcomes using real-world data, which may provide valuable evidence for managing patients with PDR in clinical practice.”1

The team collected data from patients treated with PRP alone or in combination with intravitreal anti-VEGF at the National Taiwan University Hospital or its Hsin-Chu Branch between 2019-2021. Inclusion criteria were patients with type 1 or 2 diabetes, age ≥20 years, treatment-naïve PDR confirmed by color fundus photography and fluorescein angiography, a best-corrected visual acuity (BCVA) ≥20/400, and a follow-up period of ≥12 months.1

A total of 95 eyes from 69 patients were collected, with 37 eyes from 25 patients in the PRP/anti-VEGF combination group and 58 eyes from 44 patients in the PRP group. Mean age was 54.4 years (range: 27-76 years) and neither group showed significant differences at baseline between age, sex, laterality, best-corrected visual acuity (BCVA), central retinal thickness (CRT), or PDR severity.1

The PRP group received retinal photocoagulation, the completion of which was defined as 1200-1600 scattered laser burns. These were applied in three sessions between months 0 and 2, with each session 2 weeks apart. The combined group received ranibizumab at months 0, 1, and 2, along with complete PRP treatment.1

In the PRP group, 20 eyes developed the first DME between 3 and 52 weeks after initial PRP treatment, while 3 developed DME between 22 and 36 weeks in the combined group. Combination treatment substantially reduced DME risk (cumulative incidence, 8.1% vs 31% at 12 months; P = .004). In the PRP group, 20 eyes exhibited first VH between 6 and 140 weeks after initial PRP treatment, and 10 eyes exhibited it between 17 and 136 weeks in the combined cohort. There was no significant difference in risk between the two groups (cumulative incidence, 19% vs 19.2% at 12 months; P = .8).1

Univariate analysis displayed a significant reduction in risk after initial combination treatment (cause-specific hazard ratio [csHR], 0.211; 95% CI, .060-.743, P = .015). In multivariate analysis, combined treatment lowered the DME-specific risk by almost 80% compared with PRP treatment (csHR, 0.211; 95% CI, .064-.700, P = .011).1

Multivariate analysis also indicated VH hazard decreased with age (csHR, 0.966; 95% CI, .933-.999, P = .045). The combined group exhibited superior BCVA at month 3 and 12; additionally, the combination group was less likely to need additional treatment within 1 year (adjusted OR, 0.254; 95% CI, .088-.739, P = .011).1

Lin and colleagues indicated that these results demonstrated the superiority of combination therapy in reducing the risk of DME. However, it was also noted that patients with poorly controlled blood glucose levels or a thicker baseline CRT have a higher risk of DME development.1

“Approximately one-fifth of patients may experience VH within one year despite complete PRP or combined treatment,” Lin and colleagues wrote. “Therefore, regular follow-ups are essential to maintain treatment efficacy in patients with PDR.”1

References

1. Lin H-C, Huang Y-C, Hsieh Y-T, Chang S-H. Treatment effects of panretinal photocoagulation or combined anti-vascular endothelial growth factor therapy for proliferative diabetic retinopathy on the risks of diabetic macular edema and vitreous hemorrhage. Ophthalmologica. Published online April 18, 2025:1-20. doi:10.1159/000545941

2. Reddy SV, Husain D. Panretinal photocoagulation: A review of complications. Seminars in Ophthalmology. 2017;33(1):83-88. doi:10.1080/08820538.2017.1353820