Author: Carla Santalla Castro (Spain)
Co-authors: Lucía Bascarán Oteyza, Antonio Sampedro López, Isabel Santos Rodríguez-Vigil, Cándida Viña Escalar, Álvaro Fernández-Vega Sanz, Juan Jesús Barbón García
Purpose
To report a case series of two patients who presented with retinal toxicity secondary to treatment with anti PD-1 (nivolumab) and anti PDL-1 (durvalumab) antibodies. One patient showed a bilateral diffuse uveal melanocytic proliferation (BDUMP) and the second a Vogt-Koyanagi-Harada-like syndrome (VKH). Both drugs are immunotherapeutic agents known as immune checkpoint inhibitors, which have been increasingly considered as new targets for cancer therapies.
Setting/Venue
Department of Ophthalmology, San Agustin University Hospital, Avilés, Spain.
Methods
We describe two clinical cases in which the diagnosis of retinal toxicity is based on a detailed anamnesis and complete ophthalmological assessment. Both cases present a known history of confirmed clear cell carcinoma of the kidney and the onset of symptoms occurs shortly after initiating therapy with immunomodulatory antibodies. Ancillary multimodal imaging (OCT, wide-field retinography, fluorescein angiography, and autofluorescence) and good clinical and anatomical response to oral corticosteroid therapy also support the diagnosis.
Results
Case 1.A male presented with a 4-month history of bilateral visual loss. He had multiple subretinal orange lesions with melanocytic tumors in both eyes, hypoautofluorescent and hiperfluorescent on fluorescein angiography(FA). There were macular serous detachments with intraretinal fluid in the left eye(LE), areas of retinal pigment epithelium(RPE) atrophy and sub-RPE hiperreflective deposits on optical coherence tomography(OCT). He had started treatment with durvalumab for renal carcinoma 7-months prior. Due to the good tumoral response, it was suspected BDUMP could be an inmune-related adverse event (IRAE) and steroids were started. To date, there has been partial response to treatment. Case 2.A woman with known renal carcinoma presented with bilateral ocular pain and vision loss. On examination, retrocorneal precipitates, tyndall, posterior synechiae and bilateral papilledema were found. Four months prior, she had been started on nivolumab. Lumbar puncture was unremarkable and her eye disease was considered an IRAE. Nivolumab was withdrawn and the condition responded to steroids. Two months later, she experienced further visual loss and headache. Funduscopy revealed diffuse subretinal lesions and raised whitish nodules. OCT showed retinal serous detachments and FA a delay of the choroidal filling with diffuse pooling. With a VKH-like syndrome diagnosis, steroids were restarted with full recovery.
Conlusions
Since the ocular symptoms in both of our patients begin months after starting inmunotheray, and the molecular basis of the checkpoint inhibitors may imbalance inmunologic tolerance inducing a inmune hyperreactivity, our hypothesis is that the ocular findings in our patients, very similar to those found in BDUMP and VKH syndrome, could be secondary to the non-specific inmuno activation these new inmunotherapies induce. We ruled out a paraneoplastic syndrome that would entail a bad control of his basal cancerous process or an autoinmune sistemic disease that would cause other organ manifestations. It is important to consider drug toxicity within the differential diagnosis in patients who present with visual complaints and who are known to have neoplastic processes undergoing treatment with inmunotherapy. This is especially true when the ocular symptoms are less aggressive than what it would be expected in paraneoplastic síndromes and when the tumoral response to treatment is favorable.
Financial Disclosure
None
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