Neoplasia and intraocular inflammation: From masquerade syndromes to immunotherapy-induced uveitis

Touhami, Sara; Audo, Isabelle; Terrada, C.; Gaudric, Alain; Lehoang, P.; Touitou, Valérie; Bodaghi, Bahram

doi:10.1016/j.preteyeres.2019.05.002

Cited by 39 publications

(38 citation statements)

References 384 publications

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“…Interestingly those also revealed a MAR-like ON-bipolar cell dysfunction on ERG and anti-TRPM1 autoantibodies documented by western blot and immunofluorescence on monkey retina tissue [10,44]. Consequently, as patients with carcinoma can present an ON-bipolar cell dysfunction, a better classification of these two types of paraneoplastic syndromes would be paraneoplastic with photoreceptor defect (usually addressed as CAR) and paraneoplastic with ON-bipolar defect (usually addressed as MAR) [47]. Intravitreal injection of sera from patients with MAR into monkey and mouse eyes managed by the Agence Nationale de la Recherche within the Investissements d'Avenir program (ANR-11-IDEX-0004-0) JV:Ministère de l'Enseignement Supérieur et de la Recherche.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Melanoma-associated retinopathy (MAR) is a rare paraneoplastic retinal disorder usually occurring in the context of metastatic melanoma. Patients present with night blindness, photopsias and a constriction of the visual field. MAR is an auto-immune disorder characterized by the production of autoantibodies targeting retinal proteins, especially autoantibodies reacting to the cation channel TRPM1 produced in melanocytes and ON-bipolar cells. TRPM1 has at least three different isoforms which vary in the N-terminal region of the protein. In this study, we report the case of three new MAR patients presenting different anti-TRPM1 autoantibodies reacting to the three isoforms of TRPM1 with variable binding affinity. Two sera recognized all isoforms of TRPM1, while one recognized only the two longest isoforms upon immunolocalization studies on overexpressing cells. Similarly, the former two sera reacted with all TRPM1 isoforms on western blot, but an immunoprecipitation enrichment step was necessary to detect all isoforms with the latter serum. In contrast, all sera labelled ON-bipolar cells on Tprm1 +/+ but not on Trpm1-/mouse retina as shown by coimmunolocalization. This confirms that the MAR sera specifically detect TRPM1. Most likely, the anti-TRPM1 autoantibodies of different patients vary in affinity and concentration. In addition, the binding of autoantibodies to TRPM1 may be conformation-dependent, with epitopes being inaccessible in some constructs (truncated polypeptides versus full-length TRPM1) or applications (western blotting versus immunohistochemistry).

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Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…A biopsy of the subretinal material may also be considered (but can be associated with visual morbidity) given the theoretical potential of the eye to serve as a protected reservoir for myeloma cells 15 as is known to occur in cases of intraocular lymphoma. 12 Vitreous opacities seen in this case are not typical of LCDD, and this raised suspicion for intraocular lymphoma.…”

Section: Discussionmentioning

confidence: 70%

“…Intraocular lymphoma may present with a retinal appearance similar to multiple myeloma, but it often is associated with more vitreous inflammation, the presence of yellow subretinal deposits on examination and vitreous hyperreflective foci, subretinal and sub-RPE hyperreflective deposits, and vertical hyperreflective lesions seen on OCT. [12][13][14] These features may be helpful when attempting to differentiate multiple myeloma from other neoplastic causes, but if the systemic workup is inconclusive, a diagnostic vitreous biopsy should be considered. A biopsy of the subretinal material may also be considered (but can be associated with visual morbidity) given the theoretical potential of the eye to serve as a protected reservoir for myeloma cells 15 as is known to occur in cases of intraocular lymphoma.…”

Section: Discussionmentioning

confidence: 99%

Multiple Myeloma Presenting as Recalcitrant Macular Edema

Wisely

Zhang

Grewal

2019

Journal of VitreoRetinal Diseases

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Purpose: This article presents an unusual case of ocular involvement of multiple myeloma masquerading as macular edema associated with diabetic retinopathy. Methods: A report of a single case. Results: The presence of concomitant type 2 diabetes and scattered retinal hemorrhages presented a diagnostic challenge. Large globular vitreous opacities and significant weight loss were suggestive of a neoplastic process. We demonstrate multimodal imaging findings that can be associated with plasma cell dyscrasias and also describe the purported mechanism by which plasma cell dyscrasias cause macular edema and exudative retinal detachments. Conclusion: Although multiple myeloma and related plasma cell dyscrasias are rare causes of ocular disease, they should be considered in the differential diagnosis of recalcitrant macular edema, and there should be a low threshold for systemic evaluation.

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“…Over the coming 5 to 10 years, therapeutic advances may be expected in two main areas: drugs and modes of delivery. As reviewed recently by Touhami et al, a number of new biologic agents—such as the programmed cell death protein‐1 blocker, nivolumab, and bruton tyrosine kinase inhibitor, ibrutinib—show promise for management of PCNSL, and might become candidates for intraocular injection. In parallel, experimental studies in the rabbit seek to reduce the number of injections with a biodegradable intraocular drug delivery device, or to avoid intraocular injections entirely by iontophoresis .…”

Section: Resultsmentioning

confidence: 99%

Intraocular chemotherapy for vitreoretinal lymphoma: A review

Kvopka

Lake

Smith

2019

Clinical Exper Ophthalmology

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Vitreoretinal lymphomas are rare ocular cancers, and the subset of primary central nervous system lymphomas that are based in the posterior eye. These tumours are challenging to treat, and today management generally involves a multispecialty team coordinating a treatment protocol that may include intraocular chemotherapy, ocular irradiation, systemic chemotherapy and/or autologous stem cell transplantation. The ophthalmologist has specific responsibility for the intraocular chemotherapy, which is delivered to the eye by intravitreal injection. The most commonly injected drugs are methotrexate—an anti‐metabolite—and rituximab—an anti‐human B cell monoclonal antibody. A range of intraocular chemotherapy treatment schedules have been described in the medical literature, although to date there have been no randomized clinical trials of these schedules. In this article, we review the development and current status of intraocular chemotherapy for vitreoretinal lymphoma.

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Neoplasia and intraocular inflammation: From masquerade syndromes to immunotherapy-induced uveitis

Cited by 39 publications

References 384 publications

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

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

Multiple Myeloma Presenting as Recalcitrant Macular Edema

Intraocular chemotherapy for vitreoretinal lymphoma: A review

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