Macular changes on optical coherence tomography angiography following belzutifan therapy in patients with Von-Hippel Lindau disease

Abstract

Purpose : Von-Hippel Lindau disease (VHL) is a rare genetic disease resulting in multi-system tumors including retinal hemangioblastomas (RH). Belzutifan is an oral FDA approved hypoxia-inducible factor-2α inhibitor for VHL lesions involving the kidneys and central nervous system. Studies have shown that RH can regress with belzutifan. This study analyzed the macular microvasculature changes associated with belzutifan on optical coherence tomography angiography (OCTA) in VHL patients.

Methods : This retrospective study included VHL patients with and without RH treated with belzutifan at the National Eye Institute. Patients with OCTA (Cirrus, Zeiss) performed before and after belzutifan initiation were included. Superficial (SCP) and deep capillary plexus (DCP, with projection artifacts removed) images of 3x3 and 6x6 mm scans were extracted and retinal microvascular parameters were analyzed using a validated customized automated software. The primary outcomes were change following belzutifan initiation in vessel skeleton density (VSD), vessel area density (VAD), and vessel diameter index (VDI) in a 3 mm diameter circle centered on the fovea excluding the central 1 mm diameter circle. The effect of active RH on these parameters was analyzed. Mixed models repeated measures regressions with adjustments for baseline values, age, and duration of follow-up were performed.

Results : Twenty-three eyes of 12 patients (mean age 47.5±8.2 years, 86.4% male) were included. Eight (34.8%) eyes had active RH at baseline. Mean follow-up duration was 19.6±17.8 months. Table 1 shows baseline values and changes in VSD, VAD, and VDI after belzutifan initiation. In the 3×3 mm scan, VSD increased by 0.69%/yr (P<0.0001) in the SCP and decreased by 0.14%/yr (P>0.05) in the DCP. VAD increased by 1.5%/yr (P<0.001) in the SCP, while VDI decreased by 0.54 µm/yr (P<0.01) in the SCP and increased by 0.13 µm/yr (P>0.05) in the DCP. Presence of baseline RH activity did not statistically significantly affect baseline VSD, VAD, and VDI nor change in those OCTA parameters after belzutifan initiation.

Conclusions : Treatment with belzutifan may not be associated with clinically significant changes in the macular microvasculature of patients with VHL disease, despite its effect on RH regression. The effect of belzutifan on the macular microvasculature was not influenced by the presence of active RH.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Table 1