To the Editor:

We read with interest the review “Paraneoplastic ocular syndrome: a pandora’s box of underlying malignancies” by Sarkar et al. [1], proving an overview of paraneoplastic ocular syndromes, including melanoma-associated retinopathy (MAR) [1]. It was highlighted that, although systemic immunotherapy is considered the first-line treatment for MAR, the use of immune checkpoint inhibitors can lead to immune-related adverse events, including MAR [1, 2]. We describe two cases of MAR presented after starting systemic immunotherapy.

Case 1, a 60-year woman, presented with bilateral cloudy vision during maintenance monthly nivolumab monotherapy, started after 4 cycles of ipilimumab/nivolumab, 6 months earlier. Her best-corrected visual acuity (BCVA) was 6/9 and 6/7.5 in the right and left eye, respectively, and ophthalmic examination showed bilateral anterior and intermediate uveitis. Fluorescein angiography showed minimal vasculitis and visual field (VF) test a bilateral generalized constriction, worse in the left eye.

Case 2, a 66-year man, reported positive visual symptoms and blurriness few weeks after the first cycle of ipilimumab/nivolumab. BCVA was 6/12 in both eyes. Ophthalmic examination, macular and disc OCT were unremarkable, whereas the VF showed non-specific defects in the right eye and a generalized constriction in the left eye.

In both patients, electro-diagnostic tests were indicative of MAR, showing electronegative waveform on full-field ERG and markedly attenuated ON b- and normal OFF d- wave components in both eyes (Fig. 1). Retinal autoantibodies were not investigated, as per patients’ preference; however, the evidence supporting any MAR-specific antigen is still controversial [1]. Patient 1 reported persistent significant positive visual phenomena, despite the resolution of intraocular inflammation with topical therapy and intravenous steroids performed for concomitant systemic conditions, whereas patient 2 was started on a course of oral steroids with subsequent bilateral improvement of BCVA to 6/6, stable clinical findings but persistent positive visual phenomena. Indeed, local/systemic steroids can be considered a therapeutic option in MAR [3].

Fig. 1: Electroretinogram of case 1.
figure 1

A markedly attenuated ON b- and normal OFF d- wave components in both eyes; B combined rod cone (DA3.0) and responses to high flash (DA 10.0) demonstrate a normal a-wave amplitude but severely reduced b-wave resulting in electronegative waveform on full-field ERG.

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The onset of MAR after starting immunotherapy is uncommon, as demonstrated by only 17 cases previously described [3]. However, due to the variety of symptoms and potential subclinical findings, the incidence could be underestimated [1, 4]. We strongly advice a prompt ophthalmology referral in patients with any visual symptom while on systemic immunotherapy.