Dose-Dependent and Reversible Serous Retinal Detachments in Fibroblast Growth Factor Receptor Inhibitor-Associated Retinopathy

Abstract

We report two cases of fibroblast growth factor receptor (FGFR) inhibitor-associated retinopathy, including the first case of Debio 1347 associated retinopathy manifesting with bilateral serous retinal detachments along the superotemporal arcades and a case of erdafitinib associated retinopathy manifesting with classic foveal serous retinal detachments. Both cases demonstrate a clear dose-dependent and reversible class effect likely secondary to downstream effects of FGFR inhibition on the MEK pathway, resulting in retinal pigment epithelial cell dysfunction, and may also involve additional mechanisms of cellular injury through inhibition of the PI3K/AKT/mTOR pathway. FGFR inhibitor-associated retinopathy appears to manifest differently among patients. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:xx–xx.]

Erdafitinib-induced bilateral multifocal serous retinal detachments and severe dry eye related unilateral peripheral ulcerative keratitis in a patient with metastatic urothelial carcinoma

“…The similarity between FGFR inhibitor associated retinopathy and mitogen-activated protein kinase inhibitor (MEK inhibitor) associated retinopathy was underscored. Both share comparable findings and certain ocular problems, notably bilateral, serous elevations typically involving the fovea, and fluid accumulation between the RPE and the interdigitation zone [ 5 ] . Although these are typically temporary and usually do not require therapy discontinuation, it is essential to consider the possibility of severe sight-threatening ocular symptomatology in patients with carcinomas being related to a paraneoplastic syndrome [ 16 ] .…”

“…The clinical presentation of erdafitinib-induced retinopathy has been previously identified as CSC or pseudo-CSC due to its clinical appearance on OCT sections [ 3 , 16 ] . Despite the presence of subretinal fluid and neurosensory retinal detachment; comprehensive examinations using fluorescein angiography (FA) and indocyanine green angiography (ICGA) have revealed no leakage or RPE alterations [ 5 , 7 , 9 ] . These findings suggest that erdafitinib-related retinopathy may exhibit unique characteristics.…”

“…Since then, several systemic adverse effects have been reported in association with erdafitinib such as hyponatraemia, stomatitis, asthenia, hyperphosphataemia, nail disorders, skin disorders and diarrhoea [ 2 ] . Ocular adverse effects such as dry eye [ 3 ] , conjunctivitis [ 3 ] , corneal thinning and ulceration [ 4 ] , acute-onset white cataract [ 4 ] , serous neurosensory retinal detachment [ 5 ] and subretinal pseudo-vitelliform accumulation [ 6 ] have also been reported.…”