Heterogeneity in disease activity, frequency of treatments, and visual outcomes among patients with retinal vein occlusion: relationship between injection need and vision with as-needed ranibizumab

Abstract

Background/aims: We characterised the relationships between monitoring frequency, ranibizumab injection need and vision in patients receiving as-needed (pro re nata; PRN) ranibizumab for macular oedema due to branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) in this post-hoc analysis of SHORE and HORIZON.

Methods: Patients aged 18 years and older with macular oedema due to BRVO/CRVO were included in this analysis. Injection frequency and best-corrected visual acuity (BCVA) were evaluated by PRN injection frequency in the PRN dosing phase (months (M) 7-15) of SHORE and through 12 months of HORIZON. Prespecified PRN re-treatment criteria for each trial were based on protocol-prespecified BCVA and optical coherence tomography outcomes.

Results: After the initial 7 monthly ranibizumab injections, patients in SHORE gained a mean of 18.3 letters from baseline. Patients randomised to PRN, on average, maintained these gains. However, some patients experienced additional mean gains, whereas others suffered losses (range 4.0 (95% CI 0.7 to 7.3) to -4.6 (95% CI -11.8 to 2.6) letters in patients who received 0 and 6-7 PRN injections, respectively). In BRAVO and CRUISE (lead-in trials), patients experienced mean gains from baseline to M6 (monthly dosing) of 19.3 and 15.0 letters, respectively, with gains maintained with PRN from M6 to M12. However, mean BCVA changes from baseline to M12 varied in HORIZON (range -0.4 (95% CI -2.5 to 1.6) to -3.6 (95% CI -6.2 to -1.0) letters in patients who received zero and six injections, respectively, during the preceding PRN phase of BRAVO and CRUISE).

Conclusion: The BRVO/CRVO population is heterogenous with a varied response to ranibizumab treatment.

Keywords: Angiogenesis; Clinical Trial; Macula; Retina; Treatment Medical.

Figure 1

Treatment periods in the BRAVO and CRUISE phase III trials, the HORIZON OLE and the SHORE phase IV trial. BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion; HRVO, hemiretinal vein occlusion; OLE, open-label extension; PRN, as-needed (pro re nata); q4w, every 4 weeks; q12w, every 12 weeks.

Figure 2

(A) Number of ranibizumab injections required during the PRN phase of SHORE, and mean (95% CI) BCVA change (B) from baseline and (C) from randomisation over 15 months, stratified by PRN injection frequency. Observed data from patients randomised to PRN ranibizumab at (A) M7 or M8 of SHORE (n=69), and (B, C) those with evaluable BCVA data at M15 (n=65). Error bars represent 95% CIs. BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; M, month; PRN, as-needed (pro re nata).

Figure 3

(A) Mean (95% CI) BCVA change from baseline to month 6 and end of BRAVO/CRUISE and (B) mean PRN injection frequencies and (C) BCVA outcomes over 12 months in HORIZON, stratified by PRN injection frequency during BRAVO/CRUISE (pooled retinal vein occlusion cohort). Observed data from patients who completed BRAVO/CRUISE (all treatment arms pooled) and had sufficient follow-up at each HORIZON time point. Error bars represent 95% CIs. BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; PRN, as-needed (pro re nata).

Figure 4

(A) Mean (95% CI) BCVA change from baseline to month 6 and end of BRAVO and (B) mean PRN injection frequencies and (C) BCVA outcomes over 12 months in HORIZON, stratified by PRN injection frequency during BRAVO (branch retinal vein occlusion cohort). Observed data from patients who completed BRAVO (all treatment arms pooled) and had sufficient follow-up at each HORIZON time point. Error bars represent 95% CIs. BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; PRN, as-needed (pro re nata).

Figure 5

(A) Mean (95% CI) BCVA change from baseline to month 6 and end of CRUISE and (B) mean PRN injection frequencies and (C) BCVA outcomes over 12 months in HORIZON, stratified by PRN injection frequency during CRUISE (central retinal vein occlusion cohort). Observed data from patients who completed CRUISE (all treatment arms pooled) and had sufficient follow-up at each HORIZON time point. Error bars represent 95% CIs. BCVA, best-corrected visual acuity; ETDRS, Early Treatment Diabetic Retinopathy Study; PRN, as-needed (pro re nata).