Bilateral corneal perforation in Ipilimumab/Nivolumab - associated peripheral ulcerative keratitis

Aschauer, Julia; Donner, René; Lammer, Jan; Schmidinger, Gerald

doi:10.1016/j.ajoc.2022.101686

Cited by 5 publications

(5 citation statements)

References 18 publications

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“…The majority of case reports support nivolumab continuation throughout ocular treatment because there is resolution, or at least improvement, despite its use 3 5–7 10. Refractory chronic corneal graft rejection and corneal perforation were the reasons that motivated discontinuation in three of those cases 8 9 11.…”

Section: Discussionmentioning

confidence: 99%

“…To the best of our knowledge, there are seven case reports of nivolumab-associated corneal irAEs in the literature to date (table 1). The majority describe corneal ulcerations,5–9 but some refer to keratitis,8–10 which was responsive to corticosteroid therapy and ciclosporin A. A case of chronic corneal graft rejection refractory to steroids was found 11…”

Section: Discussionmentioning

confidence: 99%

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Nivolumab-associated immune-related filamentary keratitis

Madeira,

Fernandes,

Filipe

2024

BMJ Case Rep

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A woman in her late 50s presented to the ophthalmology clinic having bilateral eye pain and discharge for the last month. Her medical history was significant for lung adenocarcinoma, for which she was being treated with nivolumab. Filamentary keratitis was evident at the slit-lamp examination. Regardless of ophthalmic reasons, nivolumab was suspended. Prednisolone ointment was started, with a complete remission. We present a case of steroid-responsive filamentary keratitis triggered by nivolumab. We aim to highlight the importance of prompt ophthalmology referral and the use of therapies targeting ocular surface inflammation in immune checkpoint inhibition therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nivolumab-associated immune-related filamentary keratitis

Madeira,

Fernandes,

Filipe

2024

BMJ Case Rep

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“…LAG-3, a type I transmembrane protein structurally akin to CD4, is accumulating evidence suggesting its pivotal role as an inhibitory coreceptor in autoimmunity, tumor immunity, and anti-infection immunity [ 2 ]. The case report underscores the potential severity of ocular irAEs associated with a novel combined ICI used for advanced systemic malignancies [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

“…While the precise pathophysiological mechanism remains unclear, stromal keratolysis is hypothesized to be initiated through an aberrant T-cell response triggering antibody production and deposition of immune complexes. This, in turn, leads to heightened chemotaxis of inflammatory cells, culminating in the destruction of proteoglycans and type I–IV collagen fibrils [ 3 , 5 , 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…While this heightened lymphocyte activation can be effective against cancer, it can also give rise to immune-related adverse events (irAEs), including anterior uveitis (1%) and keratoconjunctivitis sicca (1–24%), within other ocular and neuro-ophthalmological complications [ 1 ]. Recently, cases have emerged reporting ulcerative keratitis and keratolytic processes associated with these novel immunotherapies [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Bilateral Paracentral Corneal Melting and Left-Eye Perforation under Tobemstomig Novel Treatment

González de los Mártires,

Guerrero Pérez,

Gangoitia Gorrotxategi

et al. 2024

Case Rep Ophthalmol

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Introduction: We present a rare occurrence of bilateral corneal melting and a left-eye corneal perforation in an oncologic patient undergoing a new biological therapy. Case Presentation: A 63-year-old male with a two-day history of a painful left red eye and bilateral visual impairment was enrolled in a multicenter phase-II study comparing tobemstomig/RO7247669, a PD1-LAG3 bispecific antibody, with nivolumab. Clinical examination revealed a bilateral central corneal thinning, and corneal OCT imaging indicated a significant stromal thinning of 124 μm in the right eye and a central corneal perforation of 286 μm in the left eye. Subsequently, the patient underwent surgical intervention involving an autologous partial scleral patch with a Gundersen conjunctival flap in the left eye, alongside a comprehensive topical and systemic treatment regimen. Due to this immune-related adverse event, the patient was excluded from the clinical trial subsequently later revealing he had been on the bispecific treatment. Conclusion: While immune checkpoint inhibitors hold promise in oncology, they can lead to ocular surface issues, including dry-eye keratitis and, in severe cases, anterior segment thinning culminating in corneal perforation. Timely withdrawal of immunotherapy, coupled with multi-level treatment involving anti-inflammatory and corneal healing approaches, is crucial. In cases of corneal perforation, surgical intervention such as cyanoacrylate application or tectonic surgery becomes imperative.

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