TY - JOUR
T1 - Risk Factors and Disease Course for Blood-Brain Barrier Disruption-Associated Maculopathy
AU - Simonett, Joseph M.
AU - Skalet, Alison H.
AU - Lujan, Brandon J.
AU - Neuwelt, Edward A.
AU - Ambady, Prakash
AU - Lin, Phoebe
N1 - Funding Information:
Funding/Support: This study was supported by core grant P30 EY010572 from the National Institutes of Health and by unrestricted departmental funding from Research to Prevent Blindness. Dr Lin was supported by National Eye Institute grant K08 EY022948, a Collins Medical Trust Grant, and a Research to Prevent Blindness Career Development Award and was the recipient of an Alcon Research Institute Young Investigator Award, an Oregon Health & Science University Physician-Scientist Award, and a Thome Foundation Award.
Funding Information:
reported serving on the Castle Biosciences Advisory Board outside the submitted work. Dr Lujan reported receiving research funding from Genentech/Roche and personal fees from Regeneron, Novartis, RegenxBio, Lineage, RIBOMIC, Genentech, Southern Desert Retinal Consultants, and Translational Imaging Innovations Inc outside the submitted work. Dr Lin reported receiving an Alcon Young Investigator Award, financial support from Mallinckrodt’s advertising board, and serving on Clearside’s advertising board outside the submitted work. No other disclosures were reported.
Publisher Copyright:
© 2021 American Medical Association. All rights reserved.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Importance: Blood-brain barrier disruption (BBBD) is a systemic therapy for malignant central nervous system (CNS) tumors that has been linked to poorly understood pigmentary maculopathy. Objectives: To examine the rate of and risk factors for the development of BBBD-associated maculopathy and to assess whether there can be visually significant progression after completion of systemic therapy. Design, Setting, and Participants: In this retrospective case series, data from February 1, 2006, through December 31, 2019, were collected from patients treated with osmotic BBBD at a single tertiary referral center who had subsequent ophthalmic evaluation. Exposures: Treatment with BBBD therapy for any malignant CNS tumor. Main Outcomes and Measures: Rate and potential risk factors for developing BBBD-associated maculopathy and changes in visual acuity and retinal imaging characteristics after completion of BBBD therapy. Results: Of 283 patients treated with BBBD and chemotherapy for a CNS malignant neoplasm, 68 (mean [SD] age, 46.0 [17.9] years; 25 [38.5%] female) had an ophthalmic examination after starting systemic therapy. After excluding 3 patients because of bilateral media opacities, pigmentary maculopathy was present in 32 of 65 patients (49.2%) treated with BBBD. The number of BBBD treatment sessions, but not age, CNS malignant cancer type, or systemic chemotherapy agent, was associated with maculopathy development (odds ratio, 1.30; 95% CI, 1.12-1.50; P =.001). After completion of BBBD therapy, progressive enlargement of geographic atrophy occurred in 5 eyes of 3 patients, and choroidal neovascularization developed in 1 eye. Conclusions and Relevance: In this case series, an association was found between BBBD-related maculopathy and the number of BBBD treatment sessions, suggesting a dose-dependent effect. In some cases, maculopathy progression, including enlargement of geographic atrophy, occurred years after completion of systemic therapy. These findings may have important implications for patient education and ophthalmic monitoring.
AB - Importance: Blood-brain barrier disruption (BBBD) is a systemic therapy for malignant central nervous system (CNS) tumors that has been linked to poorly understood pigmentary maculopathy. Objectives: To examine the rate of and risk factors for the development of BBBD-associated maculopathy and to assess whether there can be visually significant progression after completion of systemic therapy. Design, Setting, and Participants: In this retrospective case series, data from February 1, 2006, through December 31, 2019, were collected from patients treated with osmotic BBBD at a single tertiary referral center who had subsequent ophthalmic evaluation. Exposures: Treatment with BBBD therapy for any malignant CNS tumor. Main Outcomes and Measures: Rate and potential risk factors for developing BBBD-associated maculopathy and changes in visual acuity and retinal imaging characteristics after completion of BBBD therapy. Results: Of 283 patients treated with BBBD and chemotherapy for a CNS malignant neoplasm, 68 (mean [SD] age, 46.0 [17.9] years; 25 [38.5%] female) had an ophthalmic examination after starting systemic therapy. After excluding 3 patients because of bilateral media opacities, pigmentary maculopathy was present in 32 of 65 patients (49.2%) treated with BBBD. The number of BBBD treatment sessions, but not age, CNS malignant cancer type, or systemic chemotherapy agent, was associated with maculopathy development (odds ratio, 1.30; 95% CI, 1.12-1.50; P =.001). After completion of BBBD therapy, progressive enlargement of geographic atrophy occurred in 5 eyes of 3 patients, and choroidal neovascularization developed in 1 eye. Conclusions and Relevance: In this case series, an association was found between BBBD-related maculopathy and the number of BBBD treatment sessions, suggesting a dose-dependent effect. In some cases, maculopathy progression, including enlargement of geographic atrophy, occurred years after completion of systemic therapy. These findings may have important implications for patient education and ophthalmic monitoring.
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U2 - 10.1001/jamaophthalmol.2020.5329
DO - 10.1001/jamaophthalmol.2020.5329
M3 - Article
C2 - 33270081
AN - SCOPUS:85097374654
VL - 139
SP - 143
EP - 149
JO - JAMA Ophthalmology
JF - JAMA Ophthalmology
SN - 2168-6165
IS - 2
ER -