Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration

Max J. Hyman; Dimitra Skondra; Nitika Aggarwal; John Moir; Nick Boucher; Brian S. McKay; Mathew W. MacCumber; Jeremy A. Lavine

doi:10.1016/j.oret.2023.04.014

Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration

Max J. Hyman, Dimitra Skondra, Nitika Aggarwal, John Moir, Nick Boucher, Brian S. McKay, Mathew W. MacCumber, Jeremy A. Lavine^*

^*Corresponding author for this work

Ophthalmology

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Objective: To determine whether levodopa (L-DOPA) is associated with a reduced likelihood of developing neovascular age-related macular degeneration (AMD). Design: Three studies were performed: retrospective analyses in the Vestrum Health Retina Database (#1–2) and case-control analysis in the Merative MarketScan Research Databases (#3). Participants: Eyes with neovascular AMD and 2 years of follow-up (#1). Eyes with non-neovascular AMD and 1 to 5 years of follow-up (#2). Patients aged ≥ 55 years with newly diagnosed neovascular AMD matched to controls without neovascular AMD (#3). Methods: Eyes were divided into 2 groups (#1–2): exposed to L-DOPA before or on the date of neovascular (#1) or nonneovascular (#2) AMD diagnosis, and eyes not exposed to L-DOPA. We extracted AMD risk factors, number of intravitreal injections (#1), and conversion rate to neovascular AMD (#2). We calculated the percentage of newly diagnosed neovascular AMD cases and matched controls exposed to any L-DOPA and determined the cumulative 2-year dose in grams by tertiles (< 100 mg, approximately 100–300 mg, and approximately > 300 mg per day, #3). Main Outcome Measures: Number of intravitreal injections (#1) and detection of new-onset neovascular AMD (#2–3) after adjusting for AMD risk factors. Results: In the Vestrum database, eyes with neovascular AMD that were exposed to L-DOPA underwent 1 fewer intravitreal injection over 2 years (N = 84 088 control vs. 530 L-DOPA eyes, P = 0.006). In eyes with nonneovascular AMD (N = 42 081–203 155 control vs. 314–1525 L-DOPA eyes), L-DOPA exposure was associated with a reduced risk of conversion to neovascular AMD by 21% at year 2 (P = 0.029), 35% at years 3 to 4 (P < 0.001), and 28% at year 5 (P = 0.024). In the MarketScan databases (N = 86 900 per group), cumulative 2-year doses of L-DOPA between approximately 100 to 300 mg per day and approximately > 300 mg were associated with decreased odds of developing neovascular AMD by 15% (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.75–0.97) and 23% (OR, 0.77; 95% CI, 0.67–0.87), respectively. Conclusions: Levodopa use was associated with reduced detection of new-onset neovascular AMD. A prospective, randomized clinical trial should be considered to investigate whether low-dose L-DOPA reduces neovascular AMD conversion. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Original language	English (US)
Pages (from-to)	745-752
Number of pages	8
Journal	Ophthalmology Retina
Volume	7
Issue number	9
DOIs	https://doi.org/10.1016/j.oret.2023.04.014
State	Published - Sep 2023

Funding

M.W.M.: Grants – Apellis Pharmaceuticals, Inc, Alimera Sciences, Inc, RegenxBio; Consultant – Regeneron, Genentech, Novartis, Bausch & Lomb, Cardinal Health, Alimera Sciences, Inc; Honoraria – Spark Therapeutics, Inc; Executive Committee – DRCR Retina Network, Illinois Society for Prevention of Blindness; Medical Leadership Board – Retina Consultants of America; Stocks – Covalent Medical.Supported by NIH grants K08 EY030923 and R01 EY034486, and the Research to Prevent Blindness Sybil B. Harrington Career Development Award for Macular Degeneration (J.A.L.). Supported by the UChicago Institute of Translational Medicine and a Bucksbaum Grant (D.S.). Supported by an Unrestricted Departmental Grant from Research to Prevent Blindness. The sponsor or funding organization had no role in the design or conduct of this research

Keywords

Age-related macular degeneration
Levodopa
Neovascular age-related macular degeneration
Parkinson's disease

ASJC Scopus subject areas

Ophthalmology

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10.1016/j.oret.2023.04.014

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@article{b91ae208a4f5476fbdf0f0cd58fc2ca4,

title = "Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration",

abstract = "Objective: To determine whether levodopa (L-DOPA) is associated with a reduced likelihood of developing neovascular age-related macular degeneration (AMD). Design: Three studies were performed: retrospective analyses in the Vestrum Health Retina Database (#1–2) and case-control analysis in the Merative MarketScan Research Databases (#3). Participants: Eyes with neovascular AMD and 2 years of follow-up (#1). Eyes with non-neovascular AMD and 1 to 5 years of follow-up (#2). Patients aged ≥ 55 years with newly diagnosed neovascular AMD matched to controls without neovascular AMD (#3). Methods: Eyes were divided into 2 groups (#1–2): exposed to L-DOPA before or on the date of neovascular (#1) or nonneovascular (#2) AMD diagnosis, and eyes not exposed to L-DOPA. We extracted AMD risk factors, number of intravitreal injections (#1), and conversion rate to neovascular AMD (#2). We calculated the percentage of newly diagnosed neovascular AMD cases and matched controls exposed to any L-DOPA and determined the cumulative 2-year dose in grams by tertiles (< 100 mg, approximately 100–300 mg, and approximately > 300 mg per day, #3). Main Outcome Measures: Number of intravitreal injections (#1) and detection of new-onset neovascular AMD (#2–3) after adjusting for AMD risk factors. Results: In the Vestrum database, eyes with neovascular AMD that were exposed to L-DOPA underwent 1 fewer intravitreal injection over 2 years (N = 84 088 control vs. 530 L-DOPA eyes, P = 0.006). In eyes with nonneovascular AMD (N = 42 081–203 155 control vs. 314–1525 L-DOPA eyes), L-DOPA exposure was associated with a reduced risk of conversion to neovascular AMD by 21% at year 2 (P = 0.029), 35% at years 3 to 4 (P < 0.001), and 28% at year 5 (P = 0.024). In the MarketScan databases (N = 86 900 per group), cumulative 2-year doses of L-DOPA between approximately 100 to 300 mg per day and approximately > 300 mg were associated with decreased odds of developing neovascular AMD by 15% (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.75–0.97) and 23% (OR, 0.77; 95% CI, 0.67–0.87), respectively. Conclusions: Levodopa use was associated with reduced detection of new-onset neovascular AMD. A prospective, randomized clinical trial should be considered to investigate whether low-dose L-DOPA reduces neovascular AMD conversion. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.",

keywords = "Age-related macular degeneration, Levodopa, Neovascular age-related macular degeneration, Parkinson's disease",

author = "Hyman, {Max J.} and Dimitra Skondra and Nitika Aggarwal and John Moir and Nick Boucher and McKay, {Brian S.} and MacCumber, {Mathew W.} and Lavine, {Jeremy A.}",

note = "Funding Information: M.W.M.: Grants – Apellis Pharmaceuticals, Inc, Alimera Sciences, Inc, RegenxBio; Consultant – Regeneron, Genentech, Novartis, Bausch & Lomb, Cardinal Health, Alimera Sciences, Inc; Honoraria – Spark Therapeutics, Inc; Executive Committee – DRCR Retina Network, Illinois Society for Prevention of Blindness; Medical Leadership Board – Retina Consultants of America; Stocks – Covalent Medical.Supported by NIH grants K08 EY030923 and R01 EY034486, and the Research to Prevent Blindness Sybil B. Harrington Career Development Award for Macular Degeneration (J.A.L.). Supported by the UChicago Institute of Translational Medicine and a Bucksbaum Grant (D.S.). Supported by an Unrestricted Departmental Grant from Research to Prevent Blindness. The sponsor or funding organization had no role in the design or conduct of this research Publisher Copyright: {\textcopyright} 2023 American Academy of Ophthalmology",

year = "2023",

month = sep,

doi = "10.1016/j.oret.2023.04.014",

language = "English (US)",

volume = "7",

pages = "745--752",

journal = "Ophthalmology Retina",

issn = "2468-7219",

publisher = "Elsevier Inc.",

number = "9",

}

TY - JOUR

T1 - Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration

AU - Hyman, Max J.

AU - Skondra, Dimitra

AU - Aggarwal, Nitika

AU - Moir, John

AU - Boucher, Nick

AU - McKay, Brian S.

AU - MacCumber, Mathew W.

AU - Lavine, Jeremy A.

N1 - Funding Information: M.W.M.: Grants – Apellis Pharmaceuticals, Inc, Alimera Sciences, Inc, RegenxBio; Consultant – Regeneron, Genentech, Novartis, Bausch & Lomb, Cardinal Health, Alimera Sciences, Inc; Honoraria – Spark Therapeutics, Inc; Executive Committee – DRCR Retina Network, Illinois Society for Prevention of Blindness; Medical Leadership Board – Retina Consultants of America; Stocks – Covalent Medical.Supported by NIH grants K08 EY030923 and R01 EY034486, and the Research to Prevent Blindness Sybil B. Harrington Career Development Award for Macular Degeneration (J.A.L.). Supported by the UChicago Institute of Translational Medicine and a Bucksbaum Grant (D.S.). Supported by an Unrestricted Departmental Grant from Research to Prevent Blindness. The sponsor or funding organization had no role in the design or conduct of this research Publisher Copyright: © 2023 American Academy of Ophthalmology

PY - 2023/9

Y1 - 2023/9

N2 - Objective: To determine whether levodopa (L-DOPA) is associated with a reduced likelihood of developing neovascular age-related macular degeneration (AMD). Design: Three studies were performed: retrospective analyses in the Vestrum Health Retina Database (#1–2) and case-control analysis in the Merative MarketScan Research Databases (#3). Participants: Eyes with neovascular AMD and 2 years of follow-up (#1). Eyes with non-neovascular AMD and 1 to 5 years of follow-up (#2). Patients aged ≥ 55 years with newly diagnosed neovascular AMD matched to controls without neovascular AMD (#3). Methods: Eyes were divided into 2 groups (#1–2): exposed to L-DOPA before or on the date of neovascular (#1) or nonneovascular (#2) AMD diagnosis, and eyes not exposed to L-DOPA. We extracted AMD risk factors, number of intravitreal injections (#1), and conversion rate to neovascular AMD (#2). We calculated the percentage of newly diagnosed neovascular AMD cases and matched controls exposed to any L-DOPA and determined the cumulative 2-year dose in grams by tertiles (< 100 mg, approximately 100–300 mg, and approximately > 300 mg per day, #3). Main Outcome Measures: Number of intravitreal injections (#1) and detection of new-onset neovascular AMD (#2–3) after adjusting for AMD risk factors. Results: In the Vestrum database, eyes with neovascular AMD that were exposed to L-DOPA underwent 1 fewer intravitreal injection over 2 years (N = 84 088 control vs. 530 L-DOPA eyes, P = 0.006). In eyes with nonneovascular AMD (N = 42 081–203 155 control vs. 314–1525 L-DOPA eyes), L-DOPA exposure was associated with a reduced risk of conversion to neovascular AMD by 21% at year 2 (P = 0.029), 35% at years 3 to 4 (P < 0.001), and 28% at year 5 (P = 0.024). In the MarketScan databases (N = 86 900 per group), cumulative 2-year doses of L-DOPA between approximately 100 to 300 mg per day and approximately > 300 mg were associated with decreased odds of developing neovascular AMD by 15% (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.75–0.97) and 23% (OR, 0.77; 95% CI, 0.67–0.87), respectively. Conclusions: Levodopa use was associated with reduced detection of new-onset neovascular AMD. A prospective, randomized clinical trial should be considered to investigate whether low-dose L-DOPA reduces neovascular AMD conversion. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

AB - Objective: To determine whether levodopa (L-DOPA) is associated with a reduced likelihood of developing neovascular age-related macular degeneration (AMD). Design: Three studies were performed: retrospective analyses in the Vestrum Health Retina Database (#1–2) and case-control analysis in the Merative MarketScan Research Databases (#3). Participants: Eyes with neovascular AMD and 2 years of follow-up (#1). Eyes with non-neovascular AMD and 1 to 5 years of follow-up (#2). Patients aged ≥ 55 years with newly diagnosed neovascular AMD matched to controls without neovascular AMD (#3). Methods: Eyes were divided into 2 groups (#1–2): exposed to L-DOPA before or on the date of neovascular (#1) or nonneovascular (#2) AMD diagnosis, and eyes not exposed to L-DOPA. We extracted AMD risk factors, number of intravitreal injections (#1), and conversion rate to neovascular AMD (#2). We calculated the percentage of newly diagnosed neovascular AMD cases and matched controls exposed to any L-DOPA and determined the cumulative 2-year dose in grams by tertiles (< 100 mg, approximately 100–300 mg, and approximately > 300 mg per day, #3). Main Outcome Measures: Number of intravitreal injections (#1) and detection of new-onset neovascular AMD (#2–3) after adjusting for AMD risk factors. Results: In the Vestrum database, eyes with neovascular AMD that were exposed to L-DOPA underwent 1 fewer intravitreal injection over 2 years (N = 84 088 control vs. 530 L-DOPA eyes, P = 0.006). In eyes with nonneovascular AMD (N = 42 081–203 155 control vs. 314–1525 L-DOPA eyes), L-DOPA exposure was associated with a reduced risk of conversion to neovascular AMD by 21% at year 2 (P = 0.029), 35% at years 3 to 4 (P < 0.001), and 28% at year 5 (P = 0.024). In the MarketScan databases (N = 86 900 per group), cumulative 2-year doses of L-DOPA between approximately 100 to 300 mg per day and approximately > 300 mg were associated with decreased odds of developing neovascular AMD by 15% (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.75–0.97) and 23% (OR, 0.77; 95% CI, 0.67–0.87), respectively. Conclusions: Levodopa use was associated with reduced detection of new-onset neovascular AMD. A prospective, randomized clinical trial should be considered to investigate whether low-dose L-DOPA reduces neovascular AMD conversion. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

KW - Age-related macular degeneration

KW - Levodopa

KW - Neovascular age-related macular degeneration

KW - Parkinson's disease

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Levodopa Is Associated with Reduced Development of Neovascular Age-Related Macular Degeneration

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