Angiogenesis, Exudation and Degeneration 2022: Spotlighting major advances in retinal diagnostics and therapies

Many of the recent advances in retina have focused on getting to the root of the causes of visual degeneration in the major retinal diseases at the cellular level.

The Angiogenesis, Exudation, and Degeneration 2022 virtual conference sponsored by the Bascom Palmer Eye Institute, Miami, Florida, United States, was at the forefront of this movement.

Presenters at the conference, a two-day event spanning 11 and 12 February, provided new evidence about detecting geography atrophy and wet and dry age-related macular degeneration (AMD) early and predicting disease progression. Investigators are also focused on finding cures for inherited retinal diseases.

Here are just a few of the groundbreaking technologies discussed at the conference.

Disease detection/progression using optical coherence tomography

OCT is an important tool for detecting AMD, and both its limitations and benefits were evaluated in disease diagnosis, patient management, and progression. One example was the application of deep learning models for detecting AMD specific features and predicting progression to late-stage AMD. Dr Emily Chew reported that deep learning used to evaluate OCT images is highly accurate for predicting progression tothe late disease stage in either neovascular disease or geographic atrophy (GA).

Swept-source OCT angiography (OCTA), Dr Seung-Young Yu reported, is valuable for staging diabetic retinopathy based on an optimal combination of nonperfusion areas seen on OCTA and the macular ganglion cell/inner plexiform layer thickness, which she described as a novel strategy.

Current and new therapies

Researchers reviewed the results achieved with the currently available anti-vascular endothelial growth factor (VEGF) therapies, those that are in the pipeline, and those that have been approved recently.

A sampling of these included an emerging therapy for nonexudative AMD, as reported by Dr David Boyer. This drug, Xiflam (InflammX Therapeutics), works by inhibiting connexin43, thus stopping the initiation of the inflammatory cascade in its tracks in AMD and diabetic retinopathy.

A second treatment, an investigational subretinal implant, the California Project to Cure Blindness Retinal Pigment Epithelium (CPCB-RPE1, Regenerative Patch Technologies), to treat advanced dry AMD, was associated with some increases in vision, as reported by Dr Amir Kashani.

Dr Glenn Jaffe reported the results with avacincaptad pegol (Zimura, Iveric Bio) in the GATHER1 trial that indicated that the 2-mg dose of the drug slowed growth of GA lesions secondary to AMD in the central area that included the fovea, and in each quadrant surrounding the central area.

GA, also studied in the DERBY and OAKS Phase 3 trials, was shown to respond to pegcetacoplan (Empaveli, Apellis Pharmaceuticals) administered monthly and every other month in the OAKS study and the drug was more efficacious in patients with baseline extrafoveal lesions. In the DERBY trial, the drug did not meet its primary endpoint, according to Dr David Lally.

The Phase 2 part A results of the KALAHARI Study found that THR-149 (Oxurion), a plasma kallikrein inhibitor, was safe and well tolerated when up to 3 injections were administered to patients with diabetic macular oedema (DMO), according to Dr Arshad M. Khanani.

The Phase 3 KESTREL and KITE studies evaluated brolucizumab for treating DMO. The results showed that the drug was comparable to results achieved with aflibercept (Eylea, Regeneron) with fewer injections needed with the 6-mg dose along with robust anatomic improvements, Dr Carl Regillo reported.

Recent approvals

The approval of the Port Delivery System (PDS) with ranibizumab (Susvimo, Roche/Genentech), caused excitement this year with its demonstrated positive results. Dr David Eichenbaum reported that device maintains the visual and anatomic outcomes over 3 years of treatment and beyond, and patients with neovascular AMD expressed a strong preference for implantation of the device over monthly anti-VEGF injections.

Another exciting advance was the approval of faricimab (Vabysmo, Genentech), reported by Dr Charles Wykoff. This treatment has the potential to have a three-pronged effect: inhibition of the disease processes of wet AMD and DMO, improvement of visual acuity (VA), and reduction of the patient treatment burden.

Dr Thomas Ciulla reported on the first drug approved for drug delivery into the suprachoroidal space. Xipere (triamcinolone acetonide injectable suspension 40 mg/ml, Clearside) was approved to treat macular oedema, the first therapy for macular oedema associated with uveitis.

Gene therapy

Netherlands investigators led by Dr Carel Hoyng have gotten to the root cause of Stargardt disease with the development of an RNA therapy that can stop the progression of the disease. Antisense oligonucleotides, a new area of drug development, prevent the gradual decline in vision that characterizes Stargardt disease by binding to the targeted RNA. These synthetic RNA molecules work to restore the proteins that are affected by the disease.

Another drug for Stargardt disease is tinlarebant (LBS-008, Belite Bio), a retinal binding protein 4 antagonist, was reported by Dr Quan Dong Nguyen to be safe and well-toleratved in adolescent patients with Stargardt disease. In addition, patients for whom VA data were available had improvements ranging from 5 to 10 letters in at least one eye. The improvements were associated with reduced autofluorescence.