Retinopathy caused by FGFR Inhibitors self limiting and reversible, finds JAMA study

Specific fibroblast growth factor receptor (FGFR) inhibitors are one of the most recent FDA-approved therapies for the treatment of FGFR-driven cancer. FGFR is involved in the activation of the mitogen activated protein kinase (MAPK) pathway and plays a role in the maintenance, survival, and repair of the RPE. As expected, several studies have reported ocular toxicity as an adverse effect during treatment, including serous retinopathy.

A retrospective study by Jasmine H. Francis, MD and team revealed that FGFR inhibitors resulted in sub retinal fluid foci similar to other drugs that inhibit the MAPK pathway. They found in the series FGFR inhibitors did not cause irreversible loss of vision; the retinopathy was self-limited and did not require medical intervention.

The findings of the study are published in JAMA Opthamalogy.

The objective of the study was to describe the clinical and morphologic characteristics of serious retinal disturbances associated with FGFR inhibitors.

The study was a retrospective case series, 146 patients receiving FGFR inhibitors as cancer treatment at a single tertiary referral center were included. This study included 40 eyes of 20 patients with retinopathy by optical coherence tomography (OCT). OCTs were obtained on the remaining patients and the results were judged normal. Patients were recruited from March 2012 to January 2021. Characteristics of treatment-emergent choroidal and retinal OCT abnormalities as compared with baseline OCT, associated with visual acuity at presentation and at fluid resolution.

The results of the study were

• A total of 20 of 146 patients (13.7%) exhibited FGFR inhibitor–associated retinopathy. Of these 20 patients, 11 (55%) were female.

• The median time from medication start to initial subretinal fluid detection was 21 (5-125; 32) days. The median baseline log MAR best-corrected visual acuity (BCVA) was 0 (0-0.1)

• At fluid accumulation, 11 eyes had decreased vision, subgroup baseline BCVA was 0 (0-0.1); and the median (IQR) BCVA change from baseline to accumulation was −0.1 (−0.2 to −0.1).

• For 26 eyes (65%) with follow-up, the subretinal fluid resolved without medical intervention or drug interruption in all except 1 patient.

• At fluid resolution, the median (IQR) BCVA was 0.1 (0-0.1), and the change in median (IQR) BCVA from baseline to fluid resolution was 0 (−0.03 to 0).

Francis, and team concluded that "FGFR inhibitors result in subretinal fluid foci similar to other drugs that inhibit the MAPK pathway. In this series, FGFR inhibitors did not cause irreversible loss of vision; the retinopathy was self-limited and did not require medical intervention."

Reference:

Francis JH, Harding JJ, Schram AM, et al. Clinical and Morphologic Characteristics of Fibroblast Growth Factor Receptor Inhibitor–Associated Retinopathy. JAMA Ophthalmol. 2021;139(10):1126–1130. doi:10.1001/jamaophthalmol.2021.3331