Effect of initial management with aflibercept vs laser photocoagulation vs observation on vision loss among patients with diabetic macular oedema: a randomised clinical trial.
Baker CW, Glassman AR, Beaulieu WT et al
JAMA. 2019; 321(10): 1880-1894
Design: This was a randomised clinical trial conducted at 91 US and Canadian sites with 702 adults with type 1 or 2 diabetes. Patients had one study eye with centre-involving diabetic macular oedema and visual acuity of 20/25 or better. Eyes were randomly assigned to receive 2.0mg of intravitreal aflibercept, focal/grid laser or observation. Aflibercept could be used as rescue therapy if visual acuity decreased from baseline during subsequent visits.
Results: At two years, the percentage of eyes with at least a five letter VA decrease was 16% in the aflibercept group, 17% in the laser group and 19% in the observation group - this was not statistically significant. One quarter of the laser group required ‘rescue’ aflibercept in the two-year period as did 34% of the observation group.
Authors concluded that observation without treatment was a reasonable strategy for centre-involving diabetic macular oedema unless visual acuity worsened.
Comment: These results give reassurance that patients with reasonable vision and centre-involving macular oedema can be safely monitored, rather than initiating active treatment, and can still maintain similar visual outcomes. From a health economics perspective, this means reduced costs, although it is important to note that close monitoring is still required, with visits at least every 16 weeks. Recent post-hoc analysis of the study groups has shown that eyes were more likely to require ‘rescue’ injections if they had greater baseline central subfield thickness, more severe diabetic retinopathy, and recent treatment in the non-study eye (JAMA Ophthalmology, online Feb 20, 2020).
Hawk and Harrier: Phase III, multicentre, randomised, double-masked trials of brolucizumab for neovascular age-related macular degeneration.
Dugel PU, Koh A, Ogura Y et al
Ophthalmology 2020; 127: 72-84
Design: A total of 1817 patients with untreated active choroidal neovascularisation, due to AMD in the study eye, were randomised to intravitreal brolucizumab 3mg or 6mg or aflibercept 2mg. After loading with three monthly injections, brolucizumab-treated eyes received an injection every 12 weeks and were interval adjusted to eight weekly if disease activity was present. Aflibercept treated eyes received eight weekly dosing.
Results: At week 48, each brolucizumab arm demonstrated non-inferiority to aflibercept in visual function and > 50% of brolucizumab-treated eyes were maintained on q 12 weekly dosing interval. Anatomical outcomes favoured brolucizumab over aflibercept, with greater central subfield thickness reductions from baseline. Adverse event rates in the study were similar in all the groups.
Comment: This study shows the efficacy of brolucizumab in treating neovascular AMD, with potential for more durability and therefore less treatment burden for patients and health services. The drug received FDA approval for use in October 2019. However, while this study showed no increase in adverse events compared to aflibercept, there have been subsequent concerns raised about safety, with the American Society of Retinal Specialists alerting members to 14 cases of retinal vasculitis after brolucizumab injections. Novartis have launched an external evaluation, but this has slowed the uptake in Australia, where it is now registered, and the US. It is not currently available in New Zealand.
24-month outcomes of inflammatory choroidal neovascularisation treated with intravitreal anti-vascular endothelial growth factors: a comparison between two treatment regimens.
Invernizzi A, Pichi F, Symes R et al
Br J Ophthalmol 2019 Nov 19. Doi: 10.1136/bjophthalmol-2019-315257 (Epub ahead of print)
Design: This study looked at 82 eyes with inflammatory choroidal neovascular membranes. It compared outcomes of those treated with a loading phase of three monthly injections, then as required, and those ‘treated as needed’ (PRN) from the beginning.
Results: Inflammatory choroidal neovascular membranes showed good response to anti-VEGF, with sustained improvements in visual acuity. The loading phase did not confer any advantage with outcomes. However, the group that received loading doses received significantly more injections (4.5 vs 2.5). The recurrence rate was similar in both groups. Authors concluded PRN treatment from the beginning was as effective.
Comment: There has been no established treatment regimen for eyes with inflammatory choroidal neovascularisation and data from macular degeneration studies cannot be extrapolated to this group. Like myopic choroidal neovascularisation, inflammatory CNV often require fewer injections to stabilise the vision and macular structure. This study helps reinforce that careful monitoring of these patients and treating only when there is clinical evidence of CNV activity is a reasonable approach. Recurrences can occur at any stage and patient education about self-monitoring vision is an important part of management.
Dr Jo Sims is a consultant ophthalmologist with subspecialist training in medical retina and uveitis. She practices at Greenlane Clinical Centre, where she set up the combined uveitis-immunology clinic, and consults at Eyes and Eyelids in Remuera, Auckland.