Multimodal analysis of macular toxicity following intra-arterial (IAC) and/or intravitreal (IVC) melphalan in retinoblastoma (Rb): evidence for infra-clinical changes by optic coherence tomography (OCT) and adaptive optics (AO)

Abstract

Purpose : Melphalan chemotherapy is widely used as first line or salvage therapy for Rb with greatly improved ocular survival. To date retinal toxicity of Melphalan has been only evaluated by full field electroretinogram (ERG). Macular integrity is however the most sensitive predictor of visual prognosis. This prompted us to investigate macular structure and function by multimodal analysis following IAC and/or IVC Melphalan injections in unilateral Rb

Methods : We retrospectively reviewed all consecutive patients with unilateral group D Rb treated by IAC and/or IVC with no primary macular involvement (tumor or exudative detachment) and having reached at least 5 years of age. Patients with secondary macular detachment or vitreo-macular traction were excluded. Treated eyes were compared with fellow healthy eyes in terms of best-corrected visual acuity (VA) after amblyopia treatment, macular automated perimetry, multifocal ERG, HRA-OCT and AO. Stereopsis was evaluated on the Lang test

Results : Five patients were included with a mean cumulative melphalan dose of 12.75mg and 215µg per eye injected by IAC and IVC respectively. Mean age at last test was 7.6 years (range 5.3-13.4). Mean VA was 0.86 (range 0.7–1.0), 1.0 for all fellow eyes. 80% had stereopsis. Treated eyes had higher values of mean deviation on macular visual field examination (6.5+/-3.5dB vs 1.6+/-0.6dB; p=0.04). Multifocal ERG analysis showed no difference between the two eyes in terms of kernel 1, 2 and 3 indexes. OCT showed higher central foveal thickness in treated eyes compared to fellow eyes (180.2+/-21.7µm vs 144.2+/-13.9µm; p=0.043) and no difference in the sub-foveal and peripapillarychoroidal thickness. Quantitative AO analysis revealed that treated eyes had comparable number of cones in superior, temporal and inferior macular areas, but significantly less in the nasal macular area (14417+/-7484 cones/mm²vs 23645+/-6048 cones/mm²; p=0.043)

Conclusions : IAC and/or IVC melphalan resulted in discrete macular toxic changes consisting of an increased non-edematous foveal thickness and a significant decrease in cones nasally to the fovea. These modifications remained mostly infraclinical and compatible with a near normal visual acuity despite the presence of treated amblyopia

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.