Treatment as Required versus Regular Monthly Treatment in the Management of Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Abstract

Background: To investigate whether treatment as required 'pro re nata' (PRN) versus regular monthly treatment regimens lead to differences in outcomes in neovascular age-related macular degeneration (nAMD). Regular monthly administration of vascular endothelial growth factor (VEGF) inhibitors is an established gold standard treatment, but this approach is costly. Replacement of monthly by PRN treatment can only be justified if there is no difference in patient relevant outcomes.

Methods: Systematic review and meta-analysis. The intervention was PRN treatment and the comparator was monthly treatment with VEGF-inhibitors. Four bibliographic databases were searched for randomised controlled trials comparing both treatment regimens directly (head-to-head studies). The last literature search was conducted in December 2014. Risk of bias assessment was performed after the Cochrane Handbook for Systematic Reviews of Interventions.

Findings: We included 3 head-to-head studies (6 reports) involving more than 2000 patients. After 2 years, the weighted mean difference in best corrected visual acuity (BCVA) was 1.9 (95% CI 0.5 to 3.3) ETDRS letters in favour of monthly treatment. Systemic adverse events were higher in PRN treated patients, but these differences were not statistically significant. After 2 years, the total number of intravitreal injections required by the patients in the PRN arms were 8.4 (95% CI 7.9 to 8.9) fewer than those having monthly treatment. The studies were considered to have a moderate risk of bias.

Conclusions: PRN treatment resulted in minor but statistically significant decrease in mean BCVA which may not be clinically meaningful. There is a small increase in risk of systemic adverse events for PRN treated patients. Overall, the results indicate that an individualized treatment approach with anti-VEGF using visual acuity and OCT-guided re-treatment criteria may be appropriate for most patients with nAMD.

Fig 1. Flow diagram outlining the screening and selection process of articles.

Fig 2. Risk of bias assessment.

Fig 3. Mean change in best corrected visual acuity (BCVA) from baseline in ETDRS letters.

Fig 4. Mean decrease in central foveal thickness (CFT) from baseline in μm.

Fig 5. Mean difference in the number of anti-VEGF injections.

Fig 6. All cause mortality.

Fig 7. All (more than one) serious systemic adverse event.

Fig 8. Arterial thromboembolic events.