Clinical Course of Paraneoplastic Retinopathy With Anti-Trpm1 Autoantibody in Japanese Cohort

Abstract

Purpose: To report the clinical course of eyes with paraneoplastic retinopathy caused by an autoantibody against transient receptor potential cation channel, subfamily M, member 1 (TRPM1). Methods: Ten paraneoplastic retinopathy patients with retinal ON-bipolar cell dysfunction, including six melanoma-associated retinopathy, from eight institutions in Japan were evaluated for the presence of an anti-TRPM1 antibody. The results of ophthalmic examinations and the presence of anti-TRPM1 antibody were analyzed. Results: Five patients were positive for the anti-TRPM1 antibody. These patients had similar clinical findings in both eyes at the time of diagnosis; relatively preserved best-corrected visual acuity, absence of fundus and optical coherence tomography abnormalities, and specific abnormalities of the electroretinography (ERG); and negative-type ERGs with bright stimulus flashes. One patient whose retinal ON-bipolar cells remained dysfunctional for the entire testing period, although the anti-TRPM1 antibody had disappeared. On the other hand, the ERGs recovered in 2 cases within 2 years after the onset. One case progressed to additional impairment of the photoreceptors with deterioration of ERGs. One case died and the clinical course was unavailable. Conclusion: Paraneoplastic retinopathy patients with retinal ON-bipolar cell dysfunction possess autoantibodies against TRPM1 at the onset of the disease process; however, the clinical course of these eyes can be different.

Identification and characterization of novel TRPM1 autoantibodies from serum of patients with melanoma-associated retinopathy

“…Similarly, on the monkey ERG, the serum suppressed the photopic b-wave, but the effect on the a-wave was similar to the one obtained with a non-MAR serum [48]. The variable sensitivity in the three sera to detect TRPM1 herein could have also different consequences of the clinical course of the patients ERGs, as some patients recovered after diagnosis and some others deteriorated as previously described [45]. However, a follow-up of the patients studied herein is not available.…”

“…However, no skin phenotype has been documented in TRPM1-related cCSNB [21][22][23]. Recently, autoantibodies against TRPM1 were identified in patients with MAR, as well as in a few patients with other neoplasms [10,11,[35][36][37][38][39][40][41][42][43][44][45][46]. Despite the fact that anti-TRPM1 autoantibodies have been mostly reported in cases of metastatic melanoma, other groups have also reported patients with carcinoma.…”

“…Whether these anti-TRPM1 antibodies cause other phenotypes such as thinning of the choroid [41] or retinal degeneration is a matter of debate [46,49]. In addition, the ocular phenotype is variable depending on the persistence or not of anti-TRPM1 autoantibodies [44,45]. Indeed, Ueno and colleagues reported clearance of autoantibodies following treatment in a patient with paraneoplastic retinopathy and ON-bipolar cell dysfunction whose ERG responses did not recover while other patients with MAR or CAR regained normal ERG responses after clearance of anti-TRPM1 antibodies [45] or following rituximab treatment [44], respectively.…”

“…In addition, the ocular phenotype is variable depending on the persistence or not of anti-TRPM1 autoantibodies [44,45]. Indeed, Ueno and colleagues reported clearance of autoantibodies following treatment in a patient with paraneoplastic retinopathy and ON-bipolar cell dysfunction whose ERG responses did not recover while other patients with MAR or CAR regained normal ERG responses after clearance of anti-TRPM1 antibodies [45] or following rituximab treatment [44], respectively. An interesting hypothesis to explain the occurrence of paraneoplastic retinopathy has been proposed in a case with a primary photoreceptor paraneoplastic retinopathy (referenced there as a case of CAR).…”

TRPM1 Autoantibodies in Melanoma Patients Without Self-Reported Visual Symptoms

“…Several groups have identified TRPM1 as the antigen targeted by MAR autoantibodies 4–8. Although TRPM1 autoantibodies are primarily associated with cutaneous melanoma, they also have been detected in patients with ovarian cancer9,10 and small cell lung cancer 5,11,12…”