June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Heritable Risk and Protective Genetic Components of Glaucoma Medication Nonadherence
Author Affiliations & Notes
  • Julie Barr
    Neuroscience, University at Buffalo, Buffalo, New York, United States
  • Michael Feehan
    Ophthalmology, University at Buffalo, Buffalo, New York, United States
  • Casey Tak
    University of Utah, Salt Lake City, Utah, United States
  • Leah Owen
    Ophthalmology and Visual Sciences, The University of Utah School of Medicine, Salt Lake City, Utah, United States
    Population Health Sciences, The University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Patrice Marie Hicks
    Ophthalmology, University of Michigan, Ann Arbor, Michigan, United States
  • Elizabeth D. Au
    Ophthalmology, University at Buffalo, Buffalo, New York, United States
  • Michael H Farkas
    Ophthalmology, University at Buffalo, Buffalo, New York, United States
    Neuroscience, University at Buffalo, Buffalo, New York, United States
  • Asher Weiner
    Ophthalmology, University at Buffalo, Buffalo, New York, United States
  • Andrew L. Reynolds
    Ophthalmology, University at Buffalo, Buffalo, New York, United States
  • Sandra Sieminski
    Ophthalmology, University at Buffalo, Buffalo, New York, United States
  • Richard Sherva
    Medicine (Biomedical Genetics), Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, United States
  • Mark M Munger
    University of Utah, Salt Lake City, Utah, United States
  • Murray H Brilliant
    Center for Human Genetics, Marshfield Clinic Health System, Marshfield, Wisconsin, United States
  • Margaret M DeAngelis
    Ophthalmology, University at Buffalo, Buffalo, New York, United States
    Ophthalmology and Visual Sciences, The University of Utah School of Medicine, Salt Lake City, Utah, United States
  • Footnotes
    Commercial Relationships   Julie Barr None; Michael Feehan None; Casey Tak None; Leah Owen None; Patrice Hicks None; Elizabeth Au None; Michael Farkas None; Asher Weiner None; Andrew Reynolds None; Sandra Sieminski None; Richard Sherva None; Mark Munger None; Murray Brilliant None; Margaret DeAngelis None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 413. doi:
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      Julie Barr, Michael Feehan, Casey Tak, Leah Owen, Patrice Marie Hicks, Elizabeth D. Au, Michael H Farkas, Asher Weiner, Andrew L. Reynolds, Sandra Sieminski, Richard Sherva, Mark M Munger, Murray H Brilliant, Margaret M DeAngelis; Heritable Risk and Protective Genetic Components of Glaucoma Medication Nonadherence. Invest. Ophthalmol. Vis. Sci. 2023;64(8):413.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Glaucoma (Gla) is the leading cause of irreversible blindness, affecting 76 million globally, and is characterized by irreversible damage to the optic nerve and retina. Pharmacotherapy manages intraocular pressure (IOP) and slow disease progression. However, adherence to Gla medications remains problematic, with only 24-59% of patients taking their medication as prescribed. Despite substantial investment in research, clinical effort and patient education protocols, nonadherence (NAd) remains high. Therefore, we aimed to determine if there is a substantive genetic component behind patients’ NAd to their Gla medication regimens.

Methods : We assessed glaucoma medication nonadherence (GMN) with prescription refill data from the Marshfield Clinic’s pharmacy dispensing database. Two standard measures were calculated: the medication possession ratio (MPR) and proportion of days covered (PDC). NAd on each metric is defined as less than 80% medication coverage over 12 months. Genome-wide level genotyping and exome sequencing was performed on 279 patients. Genome-wide complex trait analysis (GCTA) estimated the phenotypic and genotypic components of heritability of GMN through the identified SNPs from the 2.5 Illumina Chip. Exome sequencing was performed to identify significant SNPs (p-value<10-5). Ingenuity pathway analysis was utilized to derive biological meaning from any significant genes in aggregate.

Results : Over 12 months, 58.4% (MPR80) and 66.3% (PDC80) of patients were found to be NAd. GCTA demonstrated that 57% (MPR80) and 48% (PDC80) of GMN could be attributed to a genetic component. Following Bonferroni correction, the following genes were significantly associated with MPR80 NAd: GAN, SNRPE, LOC105373399, AC008271.1, WDR75, RGS1, RP11-600K15.1, and SNRPN (P<10-3); and the following with PDC80 NAd: ZMAT4, LDB2, MTUS2, SPXM2, ZNF165, TTC28, OR2W4P, OR2W2P, AL022393.7, AC096559.1, AC008271.1, and PITPNB (P<10-3). IPA analysis demonstrated that several significant pathways between both measures overlapped: opioid signaling, circadian rhythm signaling, and synaptogenesis signaling. CREB signaling in neurons was shown to have protective associations: over 50% of genes in this pathway were identified as protective against NAd.

Conclusions : Our results provide evidence for a substantial heritable genetic component to GMN (47-58%). Our findings suggest both risk and protective pathways underlying GMN.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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