Spencer Barrett, MD
Bascom Palmer Eye Institute, Miami, FL
Novel Findings from High Res OCT Talk (Dr. Freund)
Dr. K. Bailey Freund presented a talk on “Novel Findings from Innovative High-Res and Wide-Field OCT Devices”. The background for this talk demonstrated correlation of in-vivo OCT findings in Age Related Macular Degeneration (AMD) with post-mortem histology to validate current imaging technology and showed longitudinal single patient imaging findings as AMD evolves over time. It was noted that retromode near-infrared (NIR) imaging may currently be the most sensitive technique for fully detecting the extent of sub-RPE deposits. The current most widely accepted understanding for the development of large soft drusen, is that small drusen will eventually grow over time, change composition, and merge with neighboring drusen to form the late-stage phenotype seen in AMD. Dr. Freund however, proposed an alternative mechanism for the development of large soft drusen. Considering that, other than AMD, pachy-choroid disease is one of the few pathologies that frequently manifests pigmented epithelial detachments, these patients may hold clues to the pathogenesis of RPE/Bruch’s membrane interface pathology. Dr. Freund speculates that in eyes with AMD, basilar laminar depositions and small drusen can eventually merge, and along with the RPE, separate from the inner collagenous layer of Bruch’s membrane as a continuous thickened layer. This may then allow for an accumulation of lipoprotein rich lipid pools in the sub-RPE space, resembling the clinical finding of soft drusen. This mechanism may be shared with patients who present with typical pachy-choroid disease findings on OCT as well. Dr. Freund showed multiple longitudinal and cross-sectional cases that lend credibility to this potential pathogenesis in vivo with high-resolution OCT. Careful scrutiny of in vivo clinical imaging, particularly over extended follow-up intervals and using more refined retinal techniques may inform efforts to fill gaps in knowledge of the understanding of AMD progression.
SubQ MGB Injections Phase 2 Study (Dr. Singer)
Dr. Michael Singer presented a discussion on “Subcutaneous Migaldendranib (MGB) for the Treatment of Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: 9 Month Results of Chronic Dose Phase 2 Study”. Subcutaneous (subQ) migaldrendrinib is a novel, first-in-class drug in clinical development for the potential at-home treatment of wet AMD and DME. This drug, MBG, is a VEGF receptor tyrosine kinase inhibitor covalently linked to a hydroxyl dendrimer (nanomedicine), that targets inflammation without systemic side effects. This medication is ideal for chronic bilateral disease as it has the potential to treat both eyes with a single subQ administration. Its subQ administration also provides an excellent ocular safety profile. Its lack of systemic side effects is secondary to its specificity and rapid clearance. It binds to and is uptaken by RPE cells, macrophages, and microglia in choroidal neovascular lesions, and is retained by these cells for 30 days despite being renally cleared in 2 days. This study involved 27 patients (16 wet AMD/11 DME) and evaluated the safety and tolerability of subQ MGB as its primary measures. Patients included in the study had to have been treated with intravitreal injections for at least twelve weeks, demonstrated a reduction in fluid and then re-accumulated this fluid after cessation of treatment before enrollment in the study. Ultimately, the phase 2 chronic dose clinical study interim results (at 24 weeks) demonstrated that this treatment was safe and well tolerated. The most common side effect was local injection site reactions, which were typically transient and mild. There were no treatment-related systemic serious adverse events. There was a greater than 69% reduction in the need for supplemental anti-VEGF IVT in wet AMD and DME subjects. The study also demonstrated maintenance of Mean Central Subfield Thickness (CST) and Best Corrected Visual Acuity (BCVA) in wet AMD subjects, as well as maintenance of CST with modest increases in BCVA in DME subjects. Finally, there was a similar efficacy manifested in the “fellow eyes” to those being monitored in the study. Full end-study results will be presented at an upcoming conference.
