This year’s Angiogenesis, Exudation, and Degeneration—hosted by Bascom Palmer Eye Institute—was another virtual marvel with two days of exceptional education. The robust lineup included everything from the histopathology of dry AMD to the latest therapies in the pipeline for inherited retinal diseases. Here, we share highlights from the meeting.

IMAGING IN EARLY AMD

With a therapy on the horizon for dry AMD, significant work is underway to find better ways to identify early signs of atrophy. K. Bailey Freund, MD, walked attendees through several OCT and OCT angiography (OCTA) images to illustrate how histologic analysis of clinically well-documented eyes can inform current and future treatment regimens for AMD. He emphasized that failure to consider the basal laminar layer in OCT interpretation may lead to diagnostic misunderstandings. He also said that not all double-layer signs harbor macular neovascularization (MNV)—some basal laminar deposits show no signs of MNV, a finding that changes the course of therapy considerably.

Program Director Philip J. Rosenfeld, MD, PhD, discussed the power of en face OCT imaging, which has helped researchers to identify when presumed incomplete retinal pigment epithelial (RPE) and outer retinal atrophy (iRORA) is actually complete RPE and outer retinal atrophy (cRORA). AMD is a 3D disease, he said, and dense raster OCT B-scans are crucial for identifying progression to cRORA in any dimension. Horizontal B-scans just aren’t going to be enough to properly diagnose and follow wet AMD, iRORA, cRORA, and nascent geographic atrophy (GA), he emphasized.

CLINICAL IMPLICATIONS

If a therapy for dry AMD is approved, what, exactly, are clinicians going to do with it? The first day’s panel discussion tackled the tough topic with the help of a few case examples from Dr. Rosenfeld. Pravin U. Dugel, MD, noted that any potential therapy for dry AMD just might be the ultimate in personalized medicine. Because the therapies in the pipeline stave off progression rather than halt active disease, clinicians will have to look carefully at each patient’s case to determine if therapy is beneficial. If the patient has a VA of 20/20, the lesion is small, and they seem unlikely to adhere to monthly injections, it might not be worth the treatment burden, Dr. Dugel said. Conversely, if the lesion affects vision, certainly consider treating that patient, even if the lesion is small.

Robyn Guymer, MBBS, PhD, added that having an approved therapy will increase the already dire need for the identification of biomarkers that could help predict which patients are more likely to progress.

Not only that, but knowing when to stop therapy is going to be a challenge, according to Karl G. Csaky, MD, PhD. Peter K. Kaiser, MD, agreed, adding that the data show that progression curves begin to return to their normal trajectory in eyes with GA that discontinue treatment, suggesting the need for long-term, perhaps indefinite, injections.

Nancy M. Holekamp, MD, hopes that the newly approved longer-duration treatments for wet AMD will open space in her clinic for the potential onslaught of dry AMD patients in need of injections. Though she didn’t need it before, an injection clinic might be a necessary addition to her practice if a therapy for GA is approved, she said.

Of course, patient motivation will always be a factor, especially with long-term treatment regimens. While clinical trial patients are highly motivated to continue therapy, real-world outcomes will likely differ considerably, said Jeffrey S. Heier, MD. The key will be finding ways to keep patients motivated to continue treatment. His comment brought the conversation full-circle, with several panelists further expounding on the need for more research into imaging tools to help show the risk of progression—a significant motivator for patients.

AMD PIPELINE

Day two opened with a quick look at wet AMD therapies under investigation, including 1-year data for EyePoint Pharmaceutical’s DAVIO trial investigating EYP-1901 (vorolanib). Treatment with the bioerodible insert led to a 75% reduction in treatment burden at 8 months, meaning 40% of treated patients can go 8 months without supplemental injections, according to Jay S. Duker, MD. This tyrosine kinase inhibitor may be a valuable adjunct therapy with standard-of-care, he added.

Several other therapies continue to work their way through the pipeline, including UBX1325 (Unity Biotechnology), GB-102 (Graybug), OTX-TKI (Ocular Therapeutix), OPT-302 (Opthea Ltd), CLS-AX (Clearside Biomedical), and 4D-150 (4D Molecular Therapeutics). Allen C. Ho, MD, announced new data for RGX-314 (Regenxbio), including safety and efficacy data out to 3 years for cohort 3. The phase 1/2a program is complete, showing stable and improved anatomy, improvements in visual acuity, and up to an 80% reduction in treatment burden at 2 years. RGX-314 is moving into pivotal trials, according to Dr. Ho.

NEW THERAPIES

The pipeline is fun, but attendees were eager to hear about the two new therapies heading to the clinics now. The conference boasted several sessions on the port delivery system (PDS) with ranibizumab (Susvimo, Genentech/Roche). Charles C. Wykoff, MD, PhD, presented new 96-week data from the Archway trial, noting that 95% of patients did not require supplemental treatment prior to PDS refill/exchanges. Patients maintained visual acuity over the study period, but researchers noted a 3-fold higher rate of endophthalmitis compared with monthly injections, Dr. Wykoff said.

David A. Eichenbaum, MD, shared 3+ year safety and efficacy data for the PDS, which mirrored the data presented by Dr. Wykoff. Dr. Eichenbaum reviewed the ocular adverse events in more depth, noting that most complications crop up in the first year—with the exception of conjunctival erosion. “Clinicians really have to watch the conjunctiva in these patients,” he warned, considering the Portal Extension Study reported several cases of conjunctival erosion in year 4. Dr. Eichenbaum did note that all patients with late-onset ocular adverse events received the PDS early in the trials, suggesting that the surgical modifications made later in the trials may reduce the risk of complications.

The PDS sessions wrapped up with a patient-level analysis by Peter A. Campochiaro, MD. Approximately 90% of patients had no exudation after PDS implantation, and even for the 10% who did, the need for a supplemental injection was triggered by reduced vision without an increase in exudation. “Were those injections even necessary?” Dr. Campochiaro questioned. “Perhaps not.”

The discussion that followed raised a number of questions from the panel and audience, particularly concerning the increased risk of endophthalmitis and how clinicians can balance that with the benefits. While Dr. Campochiaro said the PDS is a reliable treatment option for the vast majority of AMD patients, other presenters, including Dr. Wykoff, felt clinicians will have to be careful with patient selection, at least until more real-world data is available.

Three other sessions were dedicated to faricimab (Vabysmo, Genentech/Roche) for AMD and the new 2-year data from the Tenaya and Lucerne trials. In the pooled analysis of the two studies, more than 78% of patients treated with faricimab were able to achieve dosing every 12 weeks—45% maintained a 16-week dosing regimen, according to Dr. Guymer. This, coupled with comparable vision and anatomical outcomes with monthly aflibercept (Eylea, Regeneron) injections, is the backbone of the FDA approval. When asked how clinicians should introduce the new therapy, panelist Dr. Heier said he would handle it the same way he handled the approval of aflibercept: Start with patients who have historically been unable to extend treatment and go from there.

OCTA FOR DIABETIC RETINOPATHY

The hot topic in diabetic retinopathy (DR) was OCTA, and four speakers had something to add to the conversation. Harry W. Flynn Jr, MD, kicked it off with an overview, noting that OCTA can help clinicians differentiate a slew of clinical signs, such as laser-induced choroidal neovascularization, foveal neovascularization in DR, diabetic neovascularization at the disc (NVD), diabetic neovascularization elsewhere (NVE), diabetic NVD/NVE, diabetic NVD/NVE after full scatter panretinal photocoagulation, and NVE in vitreous hemorrhage.

Seung-Young Yu, MD, explained that “mid-peripheral microvascular nonperfusion demonstrates a higher sensitivity for determining a five-grade DR compared with that obtained from the posterior macula;” thus, a combination of both 12 x 12 mm2 and 3 x 3 mm2 capillary nonperfusion area from swept-source OCTA and macular ganglion cell layer and inner plexiform layer thickness on OCT could be a novel strategy for staging DR.

Ramin Tadayoni, MD, PhD, also went to bat for OCTA, arguing that capillary nonperfusion on OCTA might be a viable substitute for color photographs when classifying DR. Still, he warned that OCTA isn’t as good at catching pathology in the periphery compared with ultra-widefield imaging, and it can miss up to 17% of proliferative DR.

Finally, Jonathan F. Russell, MD, PhD, shared a potential DR grading system using widefield swept-source OCTA that encompasses clinical findings not included in the current grading system. These findings include imaging of the entire posterior pole, the choroid, and any tractional retinal detachment; the ability to differentiate intraretinal microvascular abnormalities from neovascularization and detect diabetic macular edema; and the ability to differentiate between active and quiescent neovascularization.

FINAL THOUGHTS

This meeting, now in its third year as a virtual experience, is redefining what it means to host a successful online conference. Timely lectures from leaders in the field—many of whom tune in from their international clinics—are coupled with lively discussions and active participation from the attendee chat. The data shared and the discussions of proper implementation of new therapies will have a lasting effect on attendees.