Gamma Knife Radiosurgery for Uveal Melanoma: A Retrospective Review of Clinical Complications in a Tertiary Referral Center

Abstract

Introduction: Gamma knife radiosurgery (GKR) has shown promising results in the treatment of intraocular uveal melanoma (UM) in terms of local tumor control. However, GKR is not free from potentially sight-threatening side effects, including cataract, dry eye disease, vitreous hemorrhage, radiation retinopathy (RR), radiation maculopathy (RM), optic neuropathy, and neovascular glaucoma. The aim of this paper is to report our 20-year experience in UM management with GKR focusing on the rate of clinical treatment-induced complications.

Methods: Single-center, retrospective, observational study, including all patients with UM treated at the Ocular Oncology and Uveitis Service, in the Department of Ophthalmology of the San Raffaele Scientific Institute, Milan from September 1993 to September 2018. Clinical charts comprised complete ophthalmological examination with measurement of best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure measurement, gonioscopy, and indirect ophthalmoscopy at each visit. B-scan ultrasound (Aviso S, 10 MHz probe; Paris, France), optical coherence tomography (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany), retinography, and fundus fluorescein angiography (standard or ultra-widefield [UWF; California, Optos, Dunfermline, Scotland, UK]) were performed aiding in the diagnosis of complications.

Results: Overall, 194 patients (100 males, 51.6%) were reviewed. The median age at the time of the treatment was 65 years (range 27-89) and all participants were Caucasian. In 185 eyes (95.4%), the tumor was primarily located at the choroid. The median follow-up was 57.6 months; radiation-induced complications were found in 145 eyes (74.7%). Radiation-induced cataract and RR were the most frequent events, with a relative incidence of 41.2 and 34.5%, respectively, followed by neovascular glaucoma (27.3%), optic neuropathy (18.6%), RM (11.4%), vitreous hemorrhage (14.4%), phthisis bulbi (7.7%), hyphema (0.5%), and corneal melting (0.5%). The shorter onset of side effects involved the optic nerve (median 14.9 months) and the macula (median 13.7 months).

Conclusion: Despite modern and advanced strategies introduced to limit GKR side effects, cataract and RR still represent a serious limitation of this treatment. Incidence of RR was higher in our cohort compared to other reports, probably due to increased diagnosis rate permitted by UWF retinal imaging.

Keywords: Choroidal melanoma; Gamma knife radiosurgery; Radiation retinopathy; Ultra-widefield imaging.

Fig. 1

Spectrum of anterior segment complications of gamma knife radiosurgery. a–c Cataract, recognizable as a whitish hue of the lens behind the iris. d Neovascular glaucoma, defined as the presence of abnormal blood vessel along the pupillary border. e Corneal pannus, with complete loss of corneal transparency. f Blood in the anterior chamber and in the vitreous cavity.

Fig. 2

Spectrum of posterior segment complications of gamma knife radiosurgery. a Fundus photography of the posterior pole, revealing exudates around the optic nerve head and cotton-wool spots. b Fluorescein angiography showing temporal capillary nonperfusion. c Fundus photography showing hemorrhages in the superior retina, an indirect sign of branch retinal vein occlusion. In the periphery, laser treatment is noticeable. d, e Radiation maculopathy, with extensive exudation involving the macula (yellow halo around the pigmented lesion) and leakage of fluorescein. f, g Optical coherence tomography revealing retinal thinning, atrophy of the external retinal layers, and intraretinal edema and exudates.