Fig. 2.

Response to belzutifan in a patient with a high disease burden of RHs. Color fundus photographs of the right eye (a) and left eye (b) show multiple RHs in both eyes (dexamethasone implant visible in the vitreous cavity of the right eye) at presentation to our clinic (having previously been treated elsewhere). Late-frame fluorescein angiograms showed multiple active tumors (right eye (c) and left eye (d)). The patient underwent treatment with intravitreal anti-VEGF, intravitreal steroids, focal laser, and cryotherapy for both eyes as well as external beam radiation and pars plana vitrectomy for repair of traction retinal detachment in the right eye prior to initiation of systemic belzutifan. At this point, color fundus photographs (right eye (e) and left eye (f)) showed improvement in the tumors in both eyes. However, late-frame fluorescein angiograms showed peripheral leakage in ischemic areas of a previously treated tumor in the right eye and several small, active angiomas (red arrows) along with an early optic disc angioma (green arrow) in the left eye (right eye (g) and left eye (h)). Belzutifan was started at a dose of 80 mg PO daily with initial regression of the tumors in the left eye, followed by recurrence during a dose hold due to side effects. Two weeks after resuming the drug at a dose of 40 mg three times weekly, the right eye was stable without new tumors (i, k) and the small tumors (red arrows) and early optic disc angioma (green arrow) in the left eye had regressed both clinically and angiographically (j, l).