Melanoma-associated retinopathy with presentation of transient multiple hyper-autofluorescent dots

Melanoma-associated retinopathy (MAR) is a rare paraneoplastic syndrome occurring in patients with cutaneous melanoma. Moreover, MAR may herald a possibility of metastasis.¹ MAR is difficult to diagnose due to non-specific findings of fundus exam. Diagnosis depends on history of melanoma, symptoms of night blindness, visual field (VF) loss and electronegative b-wave on Electroretinogram (ERG).² Due to rarity of MAR, therapeutic regimen adopting cytoreduction of melanoma and immunosuppressive therapy was mostly based on reports in case series.³ Recently, there's emerging evidence on the efficacy of intravitreal dexamethasone implant on MAR.⁴

We report a case of a 47-year-old woman with a history of skin melanoma presented with sudden onset right eye vision loss and altitudinal VF deficit. No particular findings were noted in her fundus. She denied headache, joint pain, or scalp tenderness. Brain imaging was negative for inflammatory and compressive lesions. Hence, ischemic optic neuropathy (ION) was excluded. Fundus autofluorescence (FAF) of right eye showed multiple hyper-autofluorescent dots with corresponding ellipsoid zone (EZ) disruption on optical coherence tomography (OCT) (Figure 1A), which was consistent with Multiple Evanescent White Dot Syndrome (MEWDS). Meanwhile, hematologist found left axillary lymph node melanoma metastasis with BRAF V600E mutation, thus, she was prescribed with dabrafenib and trametinib. Similar clinical course occurred in the left eye 2 months later (Figure 1B). Given her recent history of melanoma recurrence and rapid course of vision loss (best corrected visual acuity [BCVA] was 2/20 in the right eye and 6/20 in the left eye) and progressive worsening of VF in both eyes, MAR with coexistent of MEWDS was suspected (Figure 1C). ERG revealed characteristic electronegative b wave (Figure 1D). After confirming MAR diagnosis, she received intravitreal dexamethasone injection and made substantial recovery in VF and ERG 1 month after first injection. Unfortunately, her symptoms recurred 3 months later, thus repeated injection of dexamethasone implant was done at 3-month interval. After 2 years of follow up, she received eight injections of dexamethasone implant in each eye and final BCVA was 20/20 in the right eye and 18/20 in the left eye. There was substantial VF recovery (Figure 1E) and ERG study showed reversal of negative b-wave in both eyes (Figure 1F). OCT showed no EZ disruption and no hyper-autofluorescent dots in both eyes (Figure 1G).

FIGURE 1. (A) Fundus autofluorescence (FAF) of right eye showed multiple hyper-autofluorescent dots along with corresponding ellipsoid zone (EZ) disruption on optical coherence tomography (OCT). (B) FAF and OCT of left eye during acute disease episode. (C) Severe visual field (VF) loss of both eyes despite steroid and target therapy. (D) Electroretinogram (ERG) of both eyes revealed electronegative b-wave (red arrow) which was typical of MAR. (E) After bilateral intravitreal injection of dexamethasone implant, both eyes showed nearly complete recovery of VF. (F) Normal ERG of both eyes was observed after dexamethasone injection. (G) Both eyes showed total recovery of EZ disruption and no more hyper-autofluorescent lesions after dexamethasone injection. MAR, melanoma-associated retinopathy; OD, right eye; OS, left eye.

To our best knowledge, this is the first case demonstrating MAR with coexistence of MEWDS in acute phase. Since both MEWDS and MAR are autoimmune related retinopathy, the autoantibodies of MAR may affect the bipolar cells, which is the target of MAR, and in the meantime, compromise the RPE and outer retinal layers, which results in the fundus findings simulating MEWDS. The fundus finding of MEWDS in our patient, ran a similar clinical course as in other patients, which vanished away within a week. In our case, cytoreduction with target therapy controlled the metastasis but did not have efficacy on MAR. In contrast, intravitreal dexamethasone implant allows complete recovery of vision, VF defect and bipolar cell dysfunction, and repeated injection seemed necessary for preventing recurrent disease. In summary, MEWDS may occur concomitantly with MAR. Intravitreal dexamethasone sustained release implant showed good therapeutic efficacy which may completely reverse the clinical course of MAR.

CONFLICT OF INTEREST STATEMENT

All authors declare no conflict of interest.