Panretinal photocoagulation (PRP) has been a mainstay for the treatment of proliferative diabetic retinopathy (PDR). Unfortunately, PRP can cause impaired contrast sensitivity, scotopic vision and visual field impairment. Furthermore, a small proportion of patients can develop severe complications from PRP, including tractional retinal detachment, diabetic vitreous hemorrhage, and neovascular glaucoma. Therefore, alternative treatments with less collateral visual impairment are actively being investigated. Given previous diabetic macular edema studies that have shown the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) in reducing severity of diabetic retinopathy, anti-VEGF has been of interest as an alternative treatment for PDR. While several studies have compared combined PRP + anti-VEGF versus PRP alone, only limited number of studies have investigated anti-VEGF monotherapy versus PRP for PDR. In this issue, Yates and colleagues present a systematic review and meta-analysis of the current literature comparing anti-VEGF monotherapy to PRP in managing PDR.
- Yates W.B.
- Mammo Z.
- Simunovic M.P.
Intravitreal anti-vascular endothelial growth factor versus panretinal LASER photocoagulation for proliferative diabetic retinopathy: a systematic review and meta-analysis.
Yates and colleagues performed a systematic review and analysis of literature found in Ovid MEDLINE, Ovid MEDLINE In-Process, CENTRAL (Cochrane Eyes and Vision Group Trials Register) and ClinicalTrials.gov. Their inclusion criteria were all randomized controlled trials investigating anti-VEGF monotherapy (either aflibercept 2 mg, ranibizumab 0.5 mg, or bevacizumab 1.25 mg) versus complete PRP monotherapy (as defined by the Diabetic Retinopathy Study) in patients ≥18 years of age with PDR from either type I or type II diabetes. Primary outcome was mean change in best-corrected visual acuity (BCVA). Secondary outcomes were the proportion of patients developing severe (<6/60) or moderate (6/24-6/60) vision loss, rates of vitrectomy or vitreous hemorrhage, center-involving macular edema (CI-DME), and reduced visual field indices.
Five studies of varying quality met the inclusion criteria (n = 632). Regarding the primary outcome (mean change in BCVA), the anti-VEGF intervention arm had a mean difference of 0.08 logMAR or 4 Early Treatment Diabetic Retinopathy Study (ETDRS) letters gained (p = 0.02) when compared with PRP at 12 months. Regarding the secondary outcomes, first, anti-VEGF led to lower likelihood of moderate vision loss when compared to PRP: risk difference (RD) 0.12. Second, there was no difference between anti-VEGF and PRP for severe vision loss (RD 0.03). Third, Anti-VEGF resulted in lower rates of vitrectomy (RD 0.10) and vitreous hemorrhage (RD 0.10) than PRP. Fourth, anti-VEGF resulted in a lower incidence of CI-DME than PRP at 12 months (RD 0.09). Last, for visual field loss, while the results could not be pooled owing to differences in testing modalities between the studies, each individual study showed: aflibercept lead to superior Esterman visual field, and ranibizumab lead to better Humphrey visual field when compared to PRP.
This meta-analysis demonstrates that anti-VEGF monotherapy may be superior to PRP in terms of the outcome measures: mean change in BCVA, visual field loss, as well as the proportions of patients with moderate vision loss, vitrectomy and vitreous hemorrhage. While these results may be in favor of anti-VEGF over PRP, Yates and his colleagues stress that it is important to keep in mind that the maintenance of treatment effect by anti-VEGF requires ongoing assessment and intervention, as the angiogenic drive continues if intravitreal anti-VEGF injections are ceased. Patients with PDR are at a high risk for blindness, which may affect up to 25% of those lost to follow-up over a 4-year period. On the other hand, the effects of PDR are presumed to be permanent. Hence, the use of anti-VEGF monotherapy without concurrent PRP should be carefully considered with the patient's likelihood of adherence to therapy and follow up. Something else to be mindful of is the modest treatment effect of anti-VEGF over PRP; although the difference is considered statistically significant, the benefit of anti-VEGF over PRP is only 4 ETDRS letter-gain at 12 months. Furthermore, examination of the treatment effect (in terms of BCVA) over the duration of the studies demonstrates that the benefit of anti-VEGF over PRP occurs in the early stage of PDR but is not sustained in the long term.
The key take-home point from this study is that while anti-VEGF may provide some benefits over PRP in PDR, clinicians should take a judicious approach to treatment selection as: 1) anti-VEGF monotherapy has higher risk of adverse visual outcome than PRP when patients are lost to follow up, and 2) the benefit of anti-VEGF over PRP may decrease in the long-term. While many retinal specialists use combination therapy of anti-VEGF and PRP, there is limited literature examining the efficacy of combination therapy. Yates and colleagues have contributed valuable information about some of the factors that need to be taken into consideration for choice of treatment.