Clinical and Morphologic Characteristics of Extracellular Signal-Regulated Kinase Inhibitor-Associated Retinopathy
Open accessAbstract
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.
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These clinical manifestations were observed in patients under ERK inhibitor treatment for metastatic cancer, and not any ocular disease.
“these clinical manifestations were observed in patients under ERK inhibitor treatment for metastatic cancer, and not any ocular disease.”
From MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges (2023) · cites this paper as [224]
Very similar clinical manifestations, but with an increased occurrence of concomitant intraretinal fluid, have also been observed in patients receiving ERK inhibitors, effects that also did not cause irreversible loss of vision or serious eye damage and that did not require medical intervention.
“Very similar clinical manifestations, but with an increased occurrence of concomitant intraretinal fluid, have also been observed in patients receiving ERK inhibitors, effects that also did not cause irreversible loss of vision or serious eye damage and that did not require medical intervention [ 224 ]”
From MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges (2023) · cites this paper as [224]
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Dummer, R., Schadendorf, D., Ascierto, P. A., Arance, A. M., Dutriaux, C., Giacomo, A. M. D., Rutkowski, P. L., Vecchio, M. D., Gutzmer, R., Mandalà, M., et al. (2017) · The Lancet Oncology · doi:10.1016/s1470-2045(17)30180-8 · Cited by 501 · see citing works
Sullivan, R. J., Infante, J. R., Jankú, F., Wong, D. J. L., Sosman, J. A., Keedy, V. L., Patel, M. R., Shapiro, G. I., Mier, J. W., Tolcher, A. W., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-1119 · Cited by 437 · see citing works
Self-citationMEK and the inhibitors: from bench to bedside
Akinleye, A., Furqan, M., Mukhi, N., Ravella, P., & Liu, D. (2013) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-6-27 · Cited by 291 · see citing works
Clinical and Morphologic Characteristics of MEK Inhibitor–Associated Retinopathy
Francis, J. H., Habib, L. A., Abramson, D. H., Yannuzzi, L. A., Heinemann, M., Gounder, M. M., Grisham, R. N., Postow, M. A., Shoushtari, A. N., Chi, P., et al. (2017) · Ophthalmology · doi:10.1016/j.ophtha.2017.05.038 · Cited by 141 · see citing works
Self-citationTransient MEK inhibitor-associated retinopathy in metastatic melanoma
Urner-Bloch, U., Urner, M., Stieger, P., Galliker, N., Winterton, N., Zubel, A., Parseval, L. M., Dummer, R., & Goldinger, S. M. (2014) · Annals of Oncology · doi:10.1093/annonc/mdu169 · Cited by 134 · see citing works
McCannel, T. A., Chmielowski, B., Finn, R. S., Goldman, J., Ribas, A., Wainberg, Z. A., & McCannel, C. A. (2014) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2014.976 · Cited by 90 · see citing works
MEK inhibitors: a new class of chemotherapeutic agents with ocular toxicity
Duncan, K. E., Chang, L. Y., & Patronas, M. (2015) · Eye · doi:10.1038/eye.2015.82 · Cited by 87 · see citing works
Subretinal Fluid Associated with MEK Inhibitor Use in the Treatment of Systemic Cancer
Weber, M. L., Liang, M. C., Flaherty, K. T., & Heier, J. S. (2016) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2016.0090 · Cited by 86 · see citing works
MEK inhibitor-associated retinopathy (MEKAR) in metastatic melanoma: Long-term ophthalmic effects
Urner-Bloch, U., Urner, M., Jaberg-Bentele, N., Frauchiger, A. L., Dummer, R., & Goldinger, S. M. (2016) · European Journal of Cancer · doi:10.1016/j.ejca.2016.06.018 · Cited by 82 · see citing works
Fouladi, M., Stewart, C. F., Blaney, S. M., Onar‐Thomas, A., Schaiquevich, P. S., Packer, R. J., Goldman, S., Geyer, J. R., Gajjar, A. J., Kun, L. E., et al. (2013) · Journal of Neuro-Oncology · doi:10.1007/s11060-013-1166-7 · Cited by 67 · see citing works
Schoenberger, S. D., & Kim, S. J. (2013) · Case Reports in Ophthalmological Medicine · doi:10.1155/2013/673796 · Cited by 46 · see citing works
Idiopathic Acute Exudative Polymorphous Vitelliform Maculopathy
BARBAZETTO, I. A., Dansingani, K. K., Dolz‐Marco, R., et al. (2017) · Ophthalmology · doi:10.1016/j.ophtha.2017.07.020 · Cited by 46 · see citing works
Niro, A., Strippoli, S., Alessio, G., Sborgia, L., Recchimurzo, N., & Guida, M. (2015) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2015.07.035 · Cited by 45 · see citing works
van Dijk, E. V., Duits, D. E. M., Versluis, M., Luyten, G., Bergen, A., Kapiteijn, E., de Lange, M., Boon, C., & van der Velden, P. (2016) · Medicine · doi:10.1097/md.0000000000003457 · Cited by 36 · see citing works
Sulochana, S. P., Jairam, R. K., Chandrasekhar, D. V., Vinod, A. B., Hiremath, R. A., Raj, A., Zainuddin, M., Bhamidipati, R. K., & Mullangi, R. (2018) · European Journal of Drug Metabolism and Pharmacokinetics · doi:10.1007/s13318-018-0465-y · Cited by 9 · see citing works
Turner, M., Rossfeld, K. K., Salama, A., Tyler, D., & Beasley, G. (2017) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2017.1299710 · Cited by 7 · see citing works
A Case of Extracellular Signal-Regulated Kinase Inhibitor–Associated Retinopathy
Sioufi, K., Das, S., & Say, E. A. T. (2020) · JAMA Ophthalmology · doi:10.1001/jamaophthalmol.2020.2716 · Cited by 6 · see citing works
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MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges
Moustardas, P., Aberdam, D., & Lagali, N. (2023) · Cells · doi:10.3390/cells12040617 · Cited by 63 · see citing works
“KO-947 [224] ERK Multifocal subretinal fluid”
Background
- 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.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Francis, Jasmine H.
- ORCID
- Venue
- Ophthalmology Retina
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 5
- Issue
- 12
- Pages
- 1187-1195
- ISSN
- 2468-6530 (ISSN-L)
- PMC
- PMC10977084
- OpenAlex
- W3171576736
- Cited by
- 15
- References
- 17
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 1
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Ophthalmology Retina (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Boehringer Ingelheim
- Mirati Therapeutics
- Research to Prevent Blindness
- Jiangsu Hengrui Medicine (US62/514, US62/685,057)
- Bristol-Myers Squibb
- Daiichi-Sankyo
- Eli Lilly and Company
- Exelixis
- National Cancer Institute (P30 CA008748)
- Bayer Fund
- GlaxoSmithKline
- Novartis
- Janssen Pharmaceuticals
- National Institutes of Health
- Pfizer
- AstraZeneca
- Topics
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
- Keywords
- serous retinal detachment, intraretinal edema, central serous chorioretinopathy, choroidal thickness, visual acuity, drug-induced retinal toxicity, metastatic cancer, outer nuclear layer
- MeSH terms
- Adult, Aged, Female, Fluorescein Angiography, Follow-Up Studies, Fundus Oculi, Humans, Male, Middle Aged, Neoplasms, Prognosis, Retrospective Studies, Visual Acuity, Tomography, Optical Coherence, Protein Kinase Inhibitors, Extracellular Signal-Regulated MAP Kinases, Retinal Pigment Epithelium, Young Adult, Central Serous Chorioretinopathy
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