Royal College of Ophthalmologists Annual Congress 2019, Glasgow - First presented and discussed on Monday 20 May 2019, with a further presentation of results during Retina Subspecialty Day on Thursday 23 May 2019.
Among patients with macular oedema secondary to central retinal vein occlusion treated with intravitreal anti-VEGF therapy through 100 weeks, EMA-licensed medications aflibercept (Eylea, Bayer) and ranibizumab (Lucentis, Novartis) were equally effective in substantially improving and maintaining vision, while compounded bevacizumab (Avastin, Roche) failed to meet predefined criteria for non-inferiority to either aflibercept or ranibizumab with respect to visual acuity outcomes.
Chief investigator of the LEAVO study Mr Philip Hykin, Moorfields Eye Hospital, London, presented the primary and secondary outcomes at 100 weeks from the LEAVO study, a multicentre phase III double-masked randomised controlled non-inferiority trial comparing bevacizumab, aflibercept and ranibizumab for macular oedema secondary to central retinal vein occlusion (CRVO) (n=463).
The primary endpoint was change in best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score from baseline to 100 weeks in the study eye of all patients.
Study design and clinical outcomes were described as robust. A linear mixed effects model was used for statistical analysis and both the intention to treat (ITT, all randomised) and per protocol (PP, eligible and sufficiently treated) populations needed to show non-inferiority (no worse) for this to be concluded. The predefined non-inferiority margin was -5 letters.
Study follow-up through the duration of the study in both the ITT and PP populations was good: 87.9% in the ITT analysis and 86.4% in the PP analysis completed the 100-week visit.
For the management of macular oedema due to CRVO, ranibizumab, aflibercept and bevacizumab provided substantial and sustained improvement in visual acuity throughout the study, said Mr Hykin.
With respect to non-inferiority for visual acuity improvement after 100 weeks of treatment, bevacizumab was not non-inferior to ranibizumab at 100 weeks, aflibercept was non-inferior to ranibizumab but not superior, and bevacizumab was not non-inferior to aflibercept at weeks 52 and 100. A summary of the main clinical outcomes is shown in Table 1.
At least 8-weekly follow-up and prompt treatment in the second year maintained first year visual acuity gains and significantly fewer injections were required with aflibercept compared with ranibizumab and bevacizumab through 100 weeks. No new safety concerns were identified and the number of adverse events was generally low across study arms. There was one case of endophthalmitis in the bevacizumab group.
For routine treatment of macular oedema due to CRVO, clinical effectiveness data from the LEAVO study do not support bevacizumab as being interchangeable with aflibercept and ranibizumab for this indication, concluded Mr Hykin.
Professor Tunde Peto, Head of NetwORC UK Reading Centre, Belfast, summarised the main imaging outcomes from the LEAVO study:
- Colour fundus photography grading correlated well with clinical diagnosis at baseline. Half of all study patients still had persistent intraretinal haemorrhage in 4 quadrants at week 100.
- On OCT, fewer patients in the bevacizumab arm were observed to have no oedema compared with the ranibizumab and aflibercept arms at week 100.
- No differences in worsening of capillary non-perfusion were identified between treatment arms on fundus fluorescein angiography.
Considerations informing clinical practice
Professor Sobha Sivaprasad, Moorfields Eye Hospital, London, highlighted several considerations informing treatment practice for CRVO-related macular oedema from both the LEAVO study and SCORE2.
Six monthly loading injections from baseline are required to provide maximal early improvement in visual acuity and at least bimonthly monitoring and timely injections are subsequently required to sustain the early visual gains.
Extension of treatment intervals beyond 8 weeks is likely to lead to loss of vision, cautioned Prof. Sivaprasad.
Table 1. Outcomes from the LEAVO study*
Abbreviations: BCVA, best corrected visual acuity; CST, central subfield thickness; OCT, optical coherence tomography; SD, standard deviation; SE, standard error.
*Completed the 100-week visit: ITT analysis 407/463 (87.9%), PP analysis 400/463 (86.4%); unadjusted mean BCVA at baseline, week 52 and week 100.