The Role of Checkpoint Inhibitors in Paraneoplastic Acute Exudative Polymorphous Vitelliform Maculopathy: Report of Two Cases

Kemels, Dieter; Berge, Josianne C. ten; Jacob, Julie A.; Schauwvlieghe, Pieter-Paul

doi:10.1097/icb.0000000000001040

Cited by 8 publications

(7 citation statements)

References 15 publications

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“…When nivolumab was reinitiated the patient simultaneously underwent a surgical resection of the primary tumor. This combination was accompanied by a significant reduction of the subretinal fluid [8]. Compared to our case, their shorter immune checkpoint inhibitor free period could partly explain why little improvement was seen.…”

Section: Discussioncontrasting

confidence: 49%

“…Miyamoto et al reported a case describing multiple bilateral serous retinal detachments and outer segment thickening without inflammation in a patient treated with the PD-1 immune checkpoint inhibitor nivolumab [3]. Kemels et al hypothesized that nivolumab indirectly provoked paraneoplastic AEPVM [8]. Harpal et al presented a case of a patient with AEPVM during vemurafenib and pembrolizumab treatment for metastatic melanoma.…”

Section: Discussionmentioning

confidence: 99%

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Acute exudative polymorphous vitelliform maculopathy during pembrolizumab treatment for metastatic melanoma: a case report

et al. 2021

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Background The use of immunomodulating therapy to treat various cancers has been on the rise and these immune checkpoint inhibitors are known to cause ocular side effects. In this article a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) is reported which developed during a first line treatment with pembrolizumab. Case presentation A 54-year-old woman was referred because of blurry vision in both eyes with a yellow spot in the central visual field of the left eye. These symptoms started after four treatments with pembrolizumab (a monoclonal antibody against the programmed cell death receptor-1) for a metastatic recurrent vaginal mucosal melanoma. Her best corrected visual acuity was 10/10 in both eyes with a correction of + 2.00 bilaterally. There were no inflammatory findings in the anterior segment or the vitreous. Fundoscopy revealed an attenuation of the foveal reflex with subtle yellow-white subretinal macular deposits (vitelliform lesions) in both eyes. Fluorescein angiography did not show staining or leakage in the mid-phase, neither a late staining. Spectral-domain optical coherence tomography of the macula illustrated bilateral neurosensory retinal detachment with a thick, highly reflective band at the outer photoreceptor segment. En face structural OCT at the level of the photoreceptors showed focal areas of increased signal corresponding to hyperreflective vitelliform material. The treatment with pembrolizumab was ceased immediately. During the following visits we slowly saw an improvement of the neurosensory retinal detachment. After almost four months a total resolution of the subretinal fluid was visualized in both eyes without the use of additional treatment, though the vitelliform deposits persisted. Conclusions The development of AEPVM in melanoma patients could be triggered by treatment with Pembrolizumab. Pembrolizumab has the potential to disturb indirectly the retinal pigment epithelium homeostasis with accumulation of lipofuscin deposits and subretinal fluid, both signs of AEPVM.

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Section: Discussioncontrasting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Acute exudative polymorphous vitelliform maculopathy during pembrolizumab treatment for metastatic melanoma: a case report

et al. 2021

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“…The exact underlying pathophysiology is not yet fully understood, but molecular mimicry is the globally accepted mechanism. Presumably, the increased antitumor response induced by ICI leads to an increased cross-reaction of antibodies against non-tumor antigens; namely against the Retinal Pigment Epithelium (RPE) in pAEPVM, against bipolar cells in MAR, and against photoreceptors in CAR [15,22,23,[29][30][31][32].…”

Section: Discussionmentioning

confidence: 99%

“…The search strategy yielded nine cases of pAEPVM related to ICI (ipilimumab n=4, nivolumab n=3, pembrolizumab n=2) [21][22][23][24][25][26][27][28]. The mean age was 62.8 years (range 46 -78).…”

Section: Paepvmmentioning

confidence: 99%

Relation between ocular paraneoplastic syndromes and Immune Checkpoint Inhibitors (ICI): review of literature

Casselman

Jacob

Schauwvlieghe

2023

J Ophthal Inflamm Infect

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Purpose To describe different ocular paraneoplastic syndromes in patients treated with Immune Checkpoint Inhibitors (ICI), its relation with different types of ICI and different types of tumors, and its implications for treatment. Methods A comprehensive review of the literature was performed. Results Patients treated with ICI can present with different ocular paraneoplastic syndromes, such as Carcinoma Associated Retinopathy (CAR), Melanoma Associated Retinopathy (MAR) and paraneoplastic Acute Exudative Polymorphous Vitelliform Maculopathy (pAEPVM). In literature, the different types of paraneoplastic retinopathy are mostly related to different types of primary tumors, with MAR and pAEPVM seen in melanoma, and CAR in carcinoma. Visual prognosis is limited in MAR and CAR. Conclusion Paraneoplastic disorders result from an antitumor immune response against a shared autoantigen between the tumor and ocular tissue. ICI enhance the antitumor immune response, which can lead to increased cross-reaction against ocular structures and unmasking of a predisposed paraneoplastic syndrome. Different types of primary tumors are related to different cross-reactive antibodies. Therefore, the different types of paraneoplastic syndromes are related to different types of primary tumors and are probably unrelated to the type of ICI. ICI-related paraneoplastic syndromes often lead to an ethical dilemma. Continuation of ICI treatment can lead to irreversible visual loss in MAR and CAR. In these cases overall survival must be weighed against quality of life. In pAEPVM however, the vitelliform lesions can disappear with tumor control, which may involve continuation of ICI.

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“…16 6 reports were excluded because visual symptoms or ocular findings were reported prior to the initiation of immunotherapy. 6 17-21 14 patients from 13 reports were included in the review [22][23][24][25][26][27][28][29][30][31][32][33][34]…”

Section: Casementioning

confidence: 99%

Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review

et al. 2022

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ObjectiveTo demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma.Methods and analysisRetrospective chart review on patients with advanced cutaneous melanoma who developed AIR after initiating immunotherapy. Complete ophthalmic examination and relevant ancillary testing were performed on each patient. The presence of AIR-associated anti-retinal antibodies was confirmed by western blot and/or immunohistochemical staining. Ophthalmic and systemic outcomes after treatment for AIR were followed over time. A systematic review of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsCase 1 developed photopsia and nyctalopia with electroretinographic findings characteristic for melanoma-associated retinopathy 1 week after initiating ipilimumab/nivolumab immunotherapy. Case 2 experienced new severe bilateral visual field loss associated with anti-retinal and anti-optic nerve antibodies while on maintenance nivolumab immunotherapy. Case 3 developed decreased visual acuity due to acute exudative polymorphous vitelliform maculopathy within 2 weeks of initiating ipilimumab/nivolumab immunotherapy. All patients had concurrent extraocular immune-related adverse events in addition to the presence of anti-retinal antibodies on serological testing. 14 published cases of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma were identified and reviewed.ConclusionsImmune checkpoint inhibition can trigger the development of AIR with varied clinical manifestations in patients with advanced cutaneous melanoma. This study highlights the need for close monitoring in cutaneous melanoma patients receiving immunotherapy who develop new visual symptoms with or without funduscopic changes, as well as the potential role for screening of patients prior to initiating immunotherapy.

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The Role of Checkpoint Inhibitors in Paraneoplastic Acute Exudative Polymorphous Vitelliform Maculopathy: Report of Two Cases

Abstract: We hypothesize that nivolumab, an immune checkpoint inhibitor, can provoke paraneoplastic acute exudative polymorphous vitelliform maculopathy by means of a tumoral immune reaction with cross-reaction against the retinal pigment epithelium.

Cited by 8 publications

References 15 publications

Acute exudative polymorphous vitelliform maculopathy during pembrolizumab treatment for metastatic melanoma: a case report

Acute exudative polymorphous vitelliform maculopathy during pembrolizumab treatment for metastatic melanoma: a case report

Relation between ocular paraneoplastic syndromes and Immune Checkpoint Inhibitors (ICI): review of literature

Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review

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