A Case of Vogt-Koyanagi-Harada Disease-Like Uveitis Induced by Nivolumab and Ipilimumab Combination Therapy

Abstract

Nivolumab and ipilimumab are widely used immune checkpoint inhibitors (ICPIs) for the treatment of metastatic melanoma. ICPIs cause an array of side effects called immune-related adverse events (IRAEs) due to activation of an immune response. ICPI-uveitis can cause irreversible vision loss if untreated. There are few reports of recurrent Vogt-Koyanagi-Harada (VKH) disease-like uveitis induced by nivolumab and ipilimumab. We report a case of VKH disease-like uveitis recurrence after resuming ICPIs. A 73-year-old man with advanced melanoma was referred to our clinic with visual loss 25 days after starting nivolumab/ipilimumab. His corrected visual acuity was 0.5 in the right eye and 0.02 in the left eye. Enhanced-depth imaging optical coherence tomography (EDI-OCT) showed marked choroid thickening. The patient was diagnosed with VKH disease-like uveitis due to IRAEs. Subtenon injection of triamcinolone acetonide was performed, and nivolumab/ipilimumab was suspended, but serous retinal detachment (SRD) markedly worsened and choroidal detachment appeared. With 2 courses of steroid pulse therapy and oral steroids, SRD disappeared, and corrected visual acuity recovered in both eyes. Five months after the first injection, exacerbation of melanoma was observed, and nivolumab and oral steroids were restarted. Six weeks later, an increase in choroidal thickness was observed with EDI-OCT and diagnosed as a recurrence of VKH disease-like uveitis. Monitoring for the recurrence of VKH disease-like uveitis during the administration of ICPIs, even after uveitis is treated, is essential. Assessment of choroidal thickness with EDI-OCT may be useful for detecting early signs of VKH disease-like uveitis.

Outcome of Nivolumab-Induced Vogt–Koyanagi–Harada Disease-Like Uveitis in a Patient Managed without Intravenous Methylprednisolone Therapy

“…Genetic phenotype and viral infection are involved in the pathogenesis of the disease [7], and several cases of VKH disease-like uveitis after the initiation of ICI, which is often used in cancer treatment in recent years, have been reported. There are 15 cases of nivolumab-induced VKH disease-like uveitis, including ours [8][9][10][11][12][13][14][15][16][17][18][19][20] (Tables 1 and 2). Ophthalmic irAE are diverse, and the most common of which is uveitis (15.1%) [2].…”

“…Nivolumab treatment was discontinued in almost all cases since 2018, after the abovementioned guideline was published. In one case, the patient presented with choroidal thickening and anterior segment inflammation after restarting nivolumab treatment [ 9 ]. Hence, caution must be observed when continuing or resuming nivolumab.…”

Tuberculosis Reactivation Demonstrated By Choroiditis And Inflammatory Choroidal Neovascular Membrane In A Patient Treated With Immune Checkpoint Inhibitors For Malignant Mucosal Melanoma

“…In addition to uveitis, potential ophthalmic IRAEs reported include orbital in ammation/ocular myositis [3,5,6], peripheral ulcerative keratitis [3], retinal vasculitis [7], melanoma associated retinopathy (MAR) like retinopathy [8], Vogt-Koyanagi Harada like posterior uveitis [9,10], cranial neuropathies [6, 11], optic neuritis [6] and ocular myasthenia [6,12]. Nivolumab is associated with the highest rate of ocular IRAEs overall whilst ipilimumab has the strongest association with uveitis [12].…”

Tuberculosis reactivation demonstrated by choroiditis and inflammatory choroidal neovascular membrane in a patient treated with immune checkpoint inhibitors for malignant mucosal melanoma

“…In addition to uveitis, potential ophthalmic IRAEs reported include orbital inflammation/ocular myositis [ 3 , 6 , 7 ], peripheral ulcerative keratitis [ 3 ], retinal vasculitis [ 8 ], melanoma associated retinopathy (MAR) like retinopathy [ 9 ], Vogt-Koyanagi Harada like posterior uveitis [ 10 , 11 ], cranial neuropathies [ 7 , 12 ], optic neuritis [ 7 ] and ocular myasthenia [ 7 , 13 ]. Nivolumab is associated with the highest rate of ocular IRAEs overall whilst ipilimumab has the strongest association with uveitis [ 13 ].…”