The Bascom Palmer Angiogenesis meeting took place on Feb. 8, covering disease pathogenesis and emerging treatment options for various retinal conditions. The presentations highlighted how some of the newest imaging modalities are helping us understand the natural course of disease and new mechanisms of action being evaluated as alternatives to our current treatments. Below is just a mere highlight of many excellent presentations at the meeting.
The identification and importance of reticular pseudodrusen
Reticular pseudodrusen identification is becoming important as studies are now showing that those with reticular pseudodrusen have a higher rate of age-related macular degeneration progression especially to geographic atrophy and significant functional changes including poor dark adaption. Identification of reticular pseudodrusen occurs in both OCT looking for subretinal deposits and by red-free color imaging.
Choriocapillaris flow and the growth rate of geographic atrophy
There was significant discussion around the measurement of choriocapillaris flow given the algorithm imbedded in most OCT devices can have some artifactual errors if various pixel sizes are used. Nonetheless, a good correlation between choriocapillaris flow voids and the location of geographic atrophy has been shown. However, the expansion of GA was not correlated to areas of poorer flow around the original lesions.
Another complement inhibitor demonstrates similar efficacy and safety signals for the treatment of geographic atrophy
Zimura (avacincaptad pegol, Iveric), when tested in 2 mg and 4 mg vs. sham for the treatment of GA, demonstrated a 27% reduction in GA growth over 12 months. The interesting safety signal (similar to C3 convertase inhibition from Apellis) was again a conversion of patients to exudation or an occurrence of neovascular AMD, seen in 9% in the Zimura-dosed patient arms vs. 2% in the sham-treated patients. Thus, the question of whether complement induces exudation vs. conversion to neovascular AMD remains to be determined in larger clinical studies.
Is gene therapy almost here for both non-neovascular and neovascular AMD?
Data from Adverum, Hemera and Regenxbio all demonstrated that intravitreal delivery of the viral vector does result in some amount of intraocular inflammation that appears to be well tolerated. However, the approach of subretinal delivery does not appear to cause significant inflammation. And in patients with neovascular AMD, few patients in all of these studies demonstrated the need for ongoing injections.
Are topical drops an option for diabetic macular edema?
Data from Oculis, utilizing a nanoparticle delivery platform with dexamethasone given topically three times a day, demonstrated an improvement in visual acuity in patients with DME alongside a reduction in retinal thickness at 12 weeks following treatment. The improvements were most pronounced in those with 20/50 or worse vision. Safety endpoints demonstrated approximately 20% of patients had an IOP rise. Additional studies are pending.
Inhibiting beyond the VEGF-A pathway for AMD
Data from the phase 2 Opthea trial demonstrated a superior improvement in both visual acuity and anatomy with its VEGF-C/D inhibitor when combined with ranibizumab over monthly ranibizumab alone. Most impressive was a reduction in choroidal neovascularization lesion size and all fluid subtypes with the addition of VEGF-C/D inhibition. Future phase 3 studies are being planned, and data from a phase 2 DME study utilizing aflibercept in combination with VEGF-C/D inhibition are awaiting readout.
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Disclosure: Singh reports he is a consultant to Zeiss, Novartis, Regeneron, Genentech and Alcon and receives grant support from Apellis and Graybug.