Angiogenesis, Exudation, and Degeneration, hosted by Bascom Palmer Eye Institute, is always packed with the latest research findings, clinical pearls, and imaging advances. This year, experts honed in on geographic atrophy (GA), diabetes, and imaging, among other topics. Here is a summary of key presentations from the 2023 virtual edition.

ADVANCES IN GA

Mengxi Shen, MD, a postdoctoral researcher at Bascom Palmer Eye Institute, explained what low luminescence visual acuity deficit (LLVAD) measures are (ie, normal luminescence letter score – low luminescence letter score) and how they correlate with central choriocapillaris perfusion. The COMPARE study began with the hypothesis that LLVAD scores would predict GA growth rate and, likely, foveal involvement over 2 years. The researchers evaluated the relationship between the central choriocapillaris flow deficits and BCVA measures in normal eyes and those with GA. The results confirmed the hypothesis, showing that increased LLVAD scores correlated with patients’ GA growth rate and that growth rate correlated with central choriocapillaris perfusion deficits. The team noted that this was the first study to confirm a correlation between choriocapillaris perfusion deficits and changes in foveal visual function. The ongoing IMPACT and SWAGGER studies continue to investigate the link between choriocapillaris flow deficit and photoreceptor loss.

The holy grail of GA therapy is reversing vision loss, which may be possible with future therapies, according to Baruch D. Kuppermann, MD, PhD. He discussed two drugs that target mitochondrial stabilization—risuteganib (Allegro Ophthalmics) and elamipretide (Stealth Biotherapeutics)—that have shown threshold OCT characteristics that may be able to predict BCVA changes with treatment. At week 28 in the phase 2 trial of risuteganib for intermediate dry AMD, 48% of study patients experienced at least an 8-letter gain in BCVA from baseline compared with 7.1% of patients in the sham arm. Predictors of treatment response included enhanced ellipsoid zone (EZ) integrity on OCT, greater outer retinal thickness on OCT, and decreased GA, Dr. Kuppermann noted. As for subcutaneous elamipretide, the phase 1 ReCLAIM study found that by the 24-week visit, low-luminescence visual acuity had improved by more than 5 letters in 53.3% of patients and more than 15 letters in 6.7% of patients. Dr. Kupperman concluded that future studies should establish thresholds, such as minimum EZ-retinal pigment epithelium (RPE) thickness, to help enroll patients who are potential responders to therapy.

Because the new and investigational GA therapies slow progression by up to 27% in clinical trials that enrolled American and European populations, Gemmy Cheung, MBBS, FRCOphth, FAMS, MCI, wondered if those results would apply to an Asian population. Research conducted by the Asia-Pacific Ocular Imaging Society Work Group suggests they may not. After studying 71 Asian patients and 73 non-Asian patients, the researchers found that GA patients who are Asian tend to have smaller lesion areas, fewer foci, and less bilateral disease. Not only that, but their GA growth rate is slower: 0.7 mm2/year versus 2.0 mm2/year, Dr. Cheung said.

OCT has become the standard imaging modality to track the progression of GA, and David Sarraf, MD, discussed the new OCT imaging parameters for detecting early, intermediate, and late AMD: incomplete RPE and outer retinal atrophy (iRORA) and complete RPE and outer retinal atrophy (cRORA).

Using these novel OCT markers, a team of researchers set out to better understand the natural conversion rate from iRORA to cRORA. They identified 42 patients (50 eyes) with imaging and at least 2 years of follow up, and they found 87 lesions that fit the OCT criteria for iRORA at baseline. The results showed that 27.5% of iRORA lesions converted to cRORA at 12 months, and 93.1% converted by the 24-month endpoint.

The team then looked at ongoing trials for GA therapies and found that the conversion rates were varied—anywhere between 30% and 60% at 12 months—depending on the study. Not only that, but the median time to conversion varied from 7 to 14 months. Although the new OCT definitions of iRORA and cRORA are a good start, Dr. Sarraf concluded that more precise parameters are needed to better identify and track early and late iRORA.

UPDATES ON HOME OCT

Daniel F. Martin, MD, presented on the Diabetic Retinopathy Clinical Research Retina Network’s Protocol AK, an observational feasibility study involving 14 patients with active choroidal neovascularization in at least one eye treated with anti-VEGF injections. The patients are conducting daily home OCT scans for 6 months and are receiving standard care for their wet AMD. In-office OCT scans are shared with the reading center to compare with the same-day home OCT scans.

Dr. Martin also described Protocol AO, a multicenter randomized clinical trial of 600 eyes with macular neovascularization; the researchers are comparing the standard treat-and-extend protocol with home OCT-guided treatment (all study eyes are treated with faricimab [Vabysmo, Genentech/Roche] injection). The goal of Protocol AO is to determine if home OCT leads to better visual outcomes and/or fewer injections over 2 years compared with the standard treat-and-extend regimen, along with gaining insight into the retinal fluid dynamics of treatment.

Anat Loewenstein, MD, discussed a study designed to identify characteristics of reactivation-treatment response episodes with home OCT, evaluate the effect of timely treatment, and elucidate the benefits of home OCT on patient care. Based on high variability in reactivation and treatment response, patients may see benefits from the personalized treatment approaches that home OCT can make possible, she said. The results showed that time to treatment after reactivation significantly affected treatment efficacy.

Nancy M. Holekamp, MD, presented on the first longitudinal study of home OCT, which involved 15 patients (29 eyes). She noted that home OCT was able to capture the heterogeneity of reactivation and treatment responses between patients, suggesting the potential benefits of personalized treatment. Also of note were the key real-world operational findings: 98% of the images captured by home OCT were of sufficient quality for artificial intelligence grading, and > 97% of patients reported a positive experience using the home OCT device. In addition, patients did not require extra support from the clinicians to perform the OCT scans at home.

DIABETIC EYE DISEASE: IMAGING AND TREATMENT

Advances in highspeed swept-source OCT angiography allow physicians to quantify retinal blood flow in capillaries with variable interscan time analysis technology, according to James G. Fujimoto, PhD. He used this imaging modality to compare examples of healthy physiology with images from patients with diabetic retinopathy (DR), which demonstrated the tool’s ability to identify markers for blood flow speed.

Toshinori Murata, MD, PhD, gave a talk on the role of drainage veins, shown on OCT angiography, in the resolution of fluid in the setting of diabetic macular edema (DME). According to the results of a phase 4 study conducted in Japan, leaking microaneurysms in the capillaries that form the foveal avascular zone led to an increased number of anti-VEGF injections required to maintain fluid resolution; therefore, the presence of a drainage vein may be important in predicting which patients may require less frequent injections for DME.

As for investigational therapies, Peter K. Kaiser, MD, presented data from the ZETA-1 phase 2b trial evaluating the safety and efficacy of APX3330 (Ocuphire), a novel oral drug candidate for DR. APX3330 targets the reduction-oxidation effector factor-1 pathway to reduce angiogenesis and inflammation. The results of the study showed that this drug demonstrated good safety and tolerability. In addition, none of the patients treated with APX3330 experienced binocular worsening of DRSS greater than 3 steps compared with 16% of untreated patients (P = .04); according to the FDA, this may be an approvable endpoint for prevention of worsening DR.

Results of the BEHOLD phase 2 trial of UBX1325 (Unity Biotechnology), a novel senolytic agent for DME, were presented by Robert Bhisitkul, MD, PhD. This drug candidate, administered by intravitreal injection, is thought to work by selectively triggering the death of senescent cells that accumulate in areas of disease activity. In the study, patients treated with a single injection gained an average of 6.2 letters at 24 weeks (P = .0084). In addition, treatment with UBX1325 combined with as-needed anti-VEFG injection led to significantly greater visual gains compared with anti-VEGF rescue alone (P = .0068). The drug was found to have a favorable safety profile with no cases of ocular inflammation.

David S. Boyer, MD, presented new 48-week data from the PHOTON trial on the safety and efficacy of 8 mg aflibercept (Regeneron) for the treatment of DME. In the study, two high-dose aflibercept groups, one dosed every 12 weeks and the other every 16 weeks, were compared with 2 mg aflibercept (Eylea, Regeneron) every 8 weeks. Both investigative arms met their primary endpoint of noninferiority in change in BCVA, gaining comparable ETDRS letters to the 2-mg group (+9.2 letters, +8.8 letters, and +7.9 letters for the 8-, 12-, and 16-week groups, respectively). In addition, 93% of patients in the 8-mg arms maintained dosing intervals of at least 12 weeks through week 48.