Melanoma‐associated retinopathy

Elsheikh, Somaia; Gurney, Sam; Burdon, Michael

doi:10.1111/ced.14095

Cited by 20 publications

(21 citation statements)

References 32 publications

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“…One patient with pre-existing glaucoma experienced ocular IrAE as the only IrAE, occurring after her first dose of pembrolizumab, and this led to treatment discontinuation. Four patients were diagnosed with anterior uveitis, one had intermediate uveitis, one had melanoma-associated retinopathy (MAR) 19,20 and one had suspected ocular ischaemic syndrome. 21 All patients had bilateral eye involvement.…”

Section: Resultsmentioning

confidence: 99%

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

et al. 2021

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Ocular immune-related adverse events (IrAEs) associated with use of checkpoint inhibitors (CPIs) in cancer therapeutics are relatively rare, occurring in approximately 1% of treated patients. Recognition and early intervention are essential because the degree of tissue damage may be disproportionate to the symptoms, and lack of appropriate treatment risks permanent loss of vision. International guidelines on managing ocular IrAEs provide limited advice only. Importantly, local interventions can be effective and may avoid the need for systemic corticosteroids, thereby permitting the continuation of CPIs. We present a single institution case series of eight affected patients managed by our multidisciplinary team. Consistent with previously published series and case reports, we identified anterior uveitis as the most common ocular IrAE associated with CPIs requiring intervention. Based on our experience, as well as published guidance, we generated a simple algorithm to assist clinicians efficiently manage patients developing ocular symptoms during treatment with CPIs. In addition, we make recommendations for optimising treatment of uveitis and address implications for ongoing CPI therapy.

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Section: Resultsmentioning

confidence: 99%

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

et al. 2021

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“…Of interest, Keltner et al suggested that the presence of MAR was associated with prolonged survival in 62 melanoma patients [ 8 ]. This has been hypothesized to be mediated by antibodies directed at specific epitopes located on melanoma cancer cell which leads to effective antitumor immunity [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Normalization of electroretinogram and symptom resolution of melanoma-associated retinopathy with negative autoantibodies after treatment with programmed death-1 (PD-1) inhibitors for metastatic melanoma

Khaddour

Khanna

Ansstas

et al. 2021

Cancer Immunol Immunother

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Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome that involves the production of autoantibodies which can cross-react with retinal epitopes leading to visual symptoms. Autoantibodies can target intracellular proteins, and only a few are directed against membrane proteins. This discrepancy in autoantibody–protein target can translate into different immune responses (T-cell mediated vs B-cell mediated). Historically, treatment of MAR has focused on surgical reduction or immunosuppressive medication, mainly glucocorticoids. However, tumor resection is not relevant in metastatic melanoma in which MAR is mostly encountered. Moreover, the use of glucocorticoids can reduce the efficacy of immunotherapy. We report the first case to our knowledge with subjective resolution of visual symptoms and objective evidence of normalization of electroretinogram of MAR with undetectable autoantibodies after administration of programmed death-1 (PD-1) inhibitor (pembrolizumab) without the use of surgical reduction or systemic immunosuppression. This case highlights the potential improvement and resolution of negative autoantibody MAR with the use of PD-1 inhibitors and emphasizes the importance of multidisciplinary approach and team discussion to avoid interventions that can decrease immunotherapy-mediated anti-tumor effect.

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“…Autoimmune retinopathies (AIR) are rare but devastating autoimmune diseases in humans, characterized by the sudden onset of severe visual deficits (or complete blindness), extinguished retinal electrical activity, relatively normal fundus appearance, and presence of serum retinal autoantibodies 9‐11 . AIRs can develop as a form of paraneoplastic syndrome (ie, CAR: cancer‐associated retinopathy; MAR: melanoma‐associated retinopathy), or in the absence of cancer (nonparaneoplastic autoimmune retinopathies: npAIR) 12‐15 . Patients suffering from npAIR can share features of CAR and MAR; however, it is believed that this retinal disease does not develop as a direct result of a cancer 13 …”

Section: Introductionmentioning

confidence: 99%

“…While there is an extensive body of literature describing the functional and morphological properties of CAR and MAR in humans, 14,27,29‐31 a description of CAR is lacking in the veterinary ophthalmology literature. A single review manuscript describes the features of possible immune‐mediated retinitis (IMR)—CAR in canine patients 2 .…”

Section: Introductionmentioning

confidence: 99%

Presumed cancer‐associated retinopathy (CAR) mimicking Sudden Acquired Retinal Degeneration Syndrome (SARDS) in canines

Grozdanić

Lazic

Kecova

et al. 2020

Veterinary Ophthalmology

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Objective To describe functional and structural features of presumed cancer‐associated retinopathy (CAR) mimicking sudden acquired retinal degeneration syndrome (SARDS) in dogs and describe treatment outcomes. Animals Subjects were 17 dogs from 8 eight US states and Canada diagnosed with SARDS or immune‐mediated retinitis (IMR) by 12 ophthalmologists. Nine eyes from seven deceased patients were used for microarray (MA), histology, or immunohistochemical (IHC) analysis. Procedures Dogs underwent complete ophthalmic examination, including retinal photography, optical coherence tomography (OCT), chromatic pupil light reflex testing (cPLR), and electroretinography (ERG), in addition to complete systemic examination. Histology, microarray, and IHC analysis were performed in CAR retinas to evaluate histological and molecular changes in retinal tissue. Results None of the patients evaluated satisfied previously established criteria for diagnosis of SARDS (flat ERG+ no red – good blue PLR), and all were diagnosed with IMR. All patients were diagnosed with a cancer: meningioma (24%), sarcoma (18%), pituitary tumor (12%), and squamous cell carcinoma (12%), other (34%). Median survival time was 6 months from diagnosis (range 1‐36 months). Most frequent systemic abnormalities were as follows: proteinuria (78%); elevated liver enzymes (47%); and metabolic changes (PU/PD, polyphagia – 24%). Immunosuppressive therapy resulted in the reversal of blindness in 44% of treated patients, with 61% of all treated patients recovering and/or maintaining vision. Median time for preservation of vision was 5 months (range 1‐35 months). Conclusions Observed changes are highly suggestive of immune‐mediated damage in IMR‐CAR eyes. A relatively high percentage of patients with CAR responded positively to immunosuppressive therapy.

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Melanoma‐associated retinopathy

Cited by 20 publications

References 32 publications

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

Normalization of electroretinogram and symptom resolution of melanoma-associated retinopathy with negative autoantibodies after treatment with programmed death-1 (PD-1) inhibitors for metastatic melanoma

Presumed cancer‐associated retinopathy (CAR) mimicking Sudden Acquired Retinal Degeneration Syndrome (SARDS) in canines

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