Angiogenesis 2019 Session VI: The Latest on Retinal Vascular Diseases, MacTel, and Uveitis

Kenneth Fan, MD
Ophthalmology Resident
Bascom Palmer Eye Institute

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

This was the final session of the 2019 Angiogenesis meeting. Thank you for joining us for the RETINA Roundup meeting coverage. The editors thank the Bascom Palmer residents and fellows for their efforts and superb work in covering all of the talks. A special thanks to Nemo Patel for organizing this series of articles. Without further ado:

Quan Dong Nguyen – Inflammation in retinal vascular disease: role of IL-6 in AMD and DME

Dr. Nguyen started the session by discussing the role of interleukin-6 (IL-6) in neovascular AMD, diabetic macular edema, and non-infectious uveitis. The discussion included a review of the HARBOR and READ-3 trials, which evaluated the association between IL-6, anti-VEGF treatment, and visual acuity in neovascular AMD and DME, respectively. IL-6 levels were found to be associated inversely with visual acuity and to be unaffected by anti-VEGF therapy.

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Michael Ip – Long-term physical stability, sterility, and anti-VEGF bioactivity of repackaged bevacizumab in 2 mL glass vials: SCORE 2

Dr. Ip then presented results from the SCORE 2 study that demonstrated that bevacizumab retained its sterility, stability, and bioactivity when stored in small glass vials for 21 months. These results are particularly useful for research study planning as it provides a more cost effective and efficient way of storing bevacizumab than in plastic syringes with shorter shelf lives.

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Darius Moshfeghi – Anti-VEGF therapy in ROP

Next, Dr. Moshfeghi reviewed the use of anti-VEGF therapy in retinopathy of prematurity (ROP), reminding us that reactivation is the rule and that fluorescein angiography is necessary in follow up to demonstrate vascular maturation. Dr. Moshfeghi then provided an overview of the highly anticipated RAINBOW trial, which evaluated outcomes at 24 weeks in ROP treated with 40% ranibizumab, 20% ranibizumab, and laser photocoagulation.

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Toshinori Murata – ZIPANGU: A comparison of anti-VEGF therapy with or without OCTA guided focal/grid laser macular edema secondary to BRVO

Dr. Murata from Japan then discussed the inability to use bevacizumab in Japan and the effects of this limitation on alternative treatment options. The talk focused on the use of OCTA-guided laser therapy to areas of capillary non-perfusion in BRVO to better eliminate VEGF drive, with the aim of reducing the anti-VEGF treatment burden, which is more costly in Japan. Preliminary results from the study in 19 of 56 patients showed no significant difference between anti-VEGF monotherapy and combination laser and anti-VEGF, but the injection burden was decreased by one injection in the combination group.

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Giovanni Straurenghi – Macular Pigment: an important technique to detect Mueller cells diseases

The conversation then shifted to the role of fundus autofluorescence imaging in the measurement of macular pigment. Dr. Straurenghi demonstrated that macular pigment levels may be an indirect sign of Mueller cell impairment, as the Mueller cells of cones are involved in the transport of macular pigment.

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Martin Friedlander – Is MacTel a serine-opathy

Dr. Friedlander then delivered a sweeping talk that indicated that systemic metabolism of serine may be involved in the pathogenesis of MacTel. The discussion demonstrated that dysfunction in the serine metabolism pathway leads to elevated levels of deoxysphingolipids, which likely play a role in eliciting the changes seen in MacTel. Interestingly, in a family of Hereditary Sensory and Autonomic Neuropathy, 13 of 14 patients examined demonstrated either MacTel or MacTel signatures, indicating the disease process may be a manifestation of systemic dysfunction.

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Glenn Jaffe – A deep learning approach to quantify ellipsoid zone loss in MacTel2 and other macular diseases

Dr. Jaffe’s discussion focused on DOCTAD, a deep-learning algorithm capable of measuring ellipsoid zone loss in MacTel2 and other macular diseases. When compared to manual segmentation in 99 eyes undergoing treatment with ciliary neurotrophic factor (CNTF), both methods demonstrated comparable outcomes, with the DOCTAD software allowing for more efficient analysis. This algorithm has the potential to be applied to other retinal disease such as AMD and Stargardt disease.

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Tom Albini – Suprachoroidal delivery of steroids in uveitis

Dr. Albini delivered a review of PEACHTREE, a phase III clinical trial, which is the first to examine suprachoroidal drug delivery for uveitic macular edema. The study evaluated the efficacy of CLS-TA in uveitic macular edema, with a primary endpoint of visual acuity improvement of three or more lines at 24 weeks. 46.9% of CLS-TA patients met the endpoint while only 15.6% of control patients did.

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Sunil Srivastava – EYS606: Non-viral gene therapy for the treatment of non infectious uveitis

The discussion then shifted to EYS606, the first non-viral gene therapy for the treatment of noninfectious uveitis. The review included a discussion of the EyeCET system for the delivery of plasmids into the ciliary muscle. The plasmid induces the expression of protein 6, a TNF alpha inhibitor. Phase II studies are currently in planning, with hopes to enroll in the United States at the end of the current year.

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Byron Lam – Treatments and clinical trials in inherited retinal degenerations

Dr. Lam gave an overview of the treatments and trials ongoing in inherited retinal degenerations. This discussion included the first ocular gene therapy with RPE65, a sequential bilateral subretinal AAV2 gene therapy, which was FDA approved in 2017. Up-and-coming therapies include Nightstar, in Phase III, for the treatment of choroideremia.

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Carel Hoyng – Clinical trials in Stargardt disease

Lastly, Dr. Hoyng reminded us that there are no current therapies available for the treatment of Stargardt disease, which is the most commonly inherited retinal dystrophy. He then reviewed the three categories of current investigation: stem cell therapy, gene therapy, and pharmacological therapies. He indicated that a limitation of gene therapy in this disease is the large size of ABCA4, which makes delivery problematic as the gene does not fit in an AV virus. Lastly, RNA antisense nucleotides are also being considered and are likely to begin clinical trials in the next 1-1.5 years.