Angiogenesis 2019 Session V: Imaging & Diabetic Retinopathy

Kenneth Fan, MD
Ophthalmology Resident
Bascom Palmer Eye Institute

Hasenin Al-Khersan, MD
Ophthalmology Resident
Bascom Palmer Eye Institute

Session V of the Angiogenesis meeting focused on macular neovascularization, diabetes, and anti-VEGF therapy. The session opened with a stimulating presentation by Stephan Michels MD who presented new developments in robot-operated intravitreal injections. Interest in this innovation piqued audible interest from the audience. This automated injection robot device would be physician-operated, also providing patient eye-tracking, remote operation, as well as sterile and comfortable technologies.

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Pravin Dugel MD presented the next lecture on post-hoc analyses of the HAWK and HARRIER studies looking at brolucizumab versus aflibercept for neovascular AMD. Promising data demonstrated that anatomical improvement with brolucizumab may be superior to aflibercept based on OCT endpoints. Furthermore, brolucizumab treated patients had more consecutive visits of fluid-free retinal anatomy after achieving fluid-free status.

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Departing from the typical presentations of the day, Andrew Moshfeghi MD MBA spoke on the social cost burden of blindness from AMD and diabetes in the U.S. healthcare system. Blindness from these two eye diseases alone is responsible for a staggering $21 billion US dollars, with AMD responsible for $16 billion and diabetic retinopathy for $5 billion. Further analyses showed that the majority cost share comes from indirect costs, such as the cost of caregivers for blind patients affected by AMD and diabetic retinopathy.

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Next, Yu Seung-Young MD presented an analysis of anatomic markers, such as macular GCIPL thickness, that may be valuable in early detection of vascular damage in diabetic retinopathy. Furthermore, mGCIPL may also be useful in predicting progression of diabetic retinopathy indicating the importance of neuroprotective therapies in delaying progression.

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Brandon Lujan MD also shed some light on the importance of anatomical markers in tracking ischemic retina. By looking at OCT, OCT angiography, and microperimetry together, his group was able to detect outer retinal loss that parallels symptoms such as visual scotomas. Additionally, ellipsoid zone loss in particular can be seen that correlates with vascular loss from retinal ischemic damage.

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Next, one of the conference co-directors, Harry Flynn Jr. MD, presented beautiful images and data emphasizing the importance of utilizing vitreoretinal interface slabs on OCT angiography to detect neovascularization of the retina in diabetic retinopathy. Furthermore, he emphasized that VRI slabs on OCTA can demonstrate subclinical neovascularization of the disc after PRP as well as choroidal neovascularization after heavy laser treatment.

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Jonathan Russell MD, a third year resident at Bascom Palmer Eye Institute, was the sole trainee to give a presentation. His excellent work paralleled the prior discussion and showed that widefield OCT angiography may be clinically comparable to ultra-widefield FA in detecting neovascularization in diabetic retinopathy. Using widefield OCTA montages, which takes 3-5 minutes in the chair and no fluorescein injection for the patient, 98-99% of neovascularization could be detected, suggesting a possible replacement for FA in diabetic retinopathy.

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Switching gears to DME, Justis Ehlers MD brought us through the VISTA DME study, investigating the viability of tracking anatomical changes of the retina in predicting visual acuity. Traditionally, central retinal thickness has not correlated with visual acuity; however, in the VISTA study, the amount of retinal fluid (retinal fluid index) as well as the ellipsoid zone exhibited good correlation with BCVA at multiple time points.

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Next, Charles Wykoff MD reported new data from the Phase 3, 1-year results of the PANORAMA study demonstrating 2-step visual acuity improvement in patients with moderate-severe NPDR and severe NPDR (without DME) treated with aflibercept. The study also showed 3-step improvement for patients as well as prevention of vision threatening complications. Though the evidence appeared to support use of aflibercept in some NPDR eyes for reducing progression and improved quality of life, he also presented data that 55% of sham eyes did not develop PDR or DME and that the study results have not yet translated into better functional outcomes.

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In a unique OCT angiography study, Ramin Tadayoni MD PhD investigated capillary non-perfusion before and after anti-VEGF therapy. His study proposed that areas of non-perfusion persisted in eyes after anti-VEGF therapy, where 29% of patients with perfusion on FA demonstrated non-perfusion on OCTA. Furthermore, though there was persistent non-perfusion after anti-VEGF treatment, clinical examination showed reduction of microaneurysms and hemorrhages, thereby affecting possibly falsely affecting ETDRS clinical staging.

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Two congruent presentations were given to wrap up the fifth session of the day. The first was given by Peter Kaiser MD who taught the audience about the implications of Tie2 receptor pathways in diabetic retinopathy and its interactions with the Tie1 receptor as well as Ang1 and Ang2 angiopoietin endothelial growth factors. He reiterated that there are several methods by which the Tie2 receptor can be targeted in treating diabetic retinopathy, and discussed the few promising clinical trials that are underway.

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Peter Campochiaro MD then reported the results of the BOULEVARD trial showing increased anatomic success and 2-step visual acuity improvement of faricimab, a new simultaneous VEGF-A and Ang2 inhibitor. Additionally, the potential of anti-Ang2 drugs was further illustrated by showing significant reduction of neovascularization when administered alongside aflibercept as compared to aflibercept alone. This talk concluded the fifth session of the Angiogenesis conference.

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