Clinical and morphologic characteristics of extracellular signal-regulated kinase inhibitor-associated retinopathy Journal Article


Authors: Francis, J. H.; Canestraro, J.; Haggag-Lindgren, D.; Harding, J. J.; Diamond, E. L.; Drilon, A.; Li, B. T.; Iyer, G.; Schram, A. M.; Abramson, D. H.
Article Title: Clinical and morphologic characteristics of extracellular signal-regulated kinase inhibitor-associated retinopathy
Abstract: Purpose: To investigate clinical and morphologic characteristics of serous retinal disturbances in patients taking extracellular signal-regulated kinase (ERK) inhibitors. Design: Single-center retrospective study of prospectively collected data. Participants: Of 61 patients receiving ERK inhibitors for treatment of metastatic cancer, this study included 40 eyes of 20 patients with evidence of retinopathy confirmed by OCT. Methods: Clinical examination, fundus photography, and OCT were used to evaluate ERK inhibitor retinopathy. The morphologic features, distribution, and location of fluid foci were evaluated serially. Visual acuity (VA) and choroidal thickness measurements were compared at baseline, fluid accumulation, and resolution. Main Outcome Measures: Characteristics of treatment-emergent choroid and retinal OCT abnormalities as compared with baseline OCT findings and the impact of toxicity on VA. Results: Of 20 patients with retinopathy, most showed fluid foci that were bilateral (100%), multifocal in each eye (75%), and with at least 1 focus involving the fovea (95%). All subretinal fluid foci occurred between the interdigitation zone and an intact retinal pigment epithelium. No statistical difference was found in choroidal thickness at fluid accumulation and resolution compared with baseline. Forty-five percent of eyes showed evidence of concomitant intraretinal edema localized to the outer nuclear layer. At the time of fluid accumulation, 57.5% eyes showed a decline in VA (mainly by 1–2 lines from baseline). For all eyes with follow-up, the subretinal fluid and intraretinal edema were reversible and resolved without medical intervention, and best-corrected VA at fluid resolution was not statistically different from baseline. Concomitant intraretinal fluid was not associated with worsening of VA. No patient discontinued or decreased drug dose because of retinopathy. Conclusions: This study showed that ERK inhibitors may cause subretinal fluid foci with unique clinical and morphologic characteristics. The observed foci were similar to mitogen-activated protein kinase kinase (MEK) inhibitor–associated retinopathy and distinct from central serous chorioretinopathy. However, unlike with MEK inhibitors, an increased occurrence of concomitant intraretinal fluid without significant additive visual impact seems to occur with ERK inhibitors. In this series, ERK inhibitors did not cause irreversible loss of vision or serious eye damage; retinopathy was self-limited and did not require medical intervention. © 2021 American Academy of Ophthalmology
Keywords: adolescent; adult; aged; major clinical study; hypertension; follow up; cancer diagnosis; colorectal cancer; melanoma; metastasis; multiple cycle treatment; mitogen activated protein kinase inhibitor; retrospective study; prostate cancer; diabetes mellitus; retinopathy; retina; intraocular pressure; hydrocortisone; gastroesophageal reflux; blindness; sildenafil; eye toxicity; ophthalmology; optical coherence tomography; eye photography; visual acuity; subretinal fluid; mek inhibitor; autofluorescence; eye fundus; chorioretinopathy; human; male; female; article; retinal pigment epithelium; best corrected visual acuity; choroidal thickness; central serous chorioretinopathy; ulixertinib; erk inhibitor; retina edema
Journal Title: Ophthalmology Retina
Volume: 5
Issue: 12
ISSN: 2468-6530
Publisher: Elsevier Inc.  
Date Published: 2021-12-01
Start Page: 1187
End Page: 1195
Language: English
DOI: 10.1016/j.oret.2021.06.001
PUBMED: 34102344
PROVIDER: scopus
PMCID: PMC10977084
DOI/URL:
Notes: Article -- Export Date: 3 January 2022 -- Source: Scopus
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MSK Authors
  1. Jasmine Helen Francis
    256 Francis
  2. James Joseph Harding
    250 Harding
  3. David H Abramson
    389 Abramson
  4. Gopakumar Vasudeva Iyer
    342 Iyer
  5. Alexander Edward Drilon
    632 Drilon
  6. Alison Michele Schram
    122 Schram
  7. Eli Louis Diamond
    202 Diamond
  8. Bob Tingkan Li
    278 Li
  9. Dianna May Haggag
    3 Haggag