Glaucoma Examination in the Amish of Holmes County, Ohio

Abstract

Purpose : Despite extensive efforts to understand the genetics of glaucoma, we still do not have the full genetic profile of any of the major types – primary open-angle glaucoma, primary angle closure glaucoma, pigmentary glaucoma, or exfoliation glaucoma. Our goal was to determine if glaucoma is present in the Amish in Holmes County, Ohio, a unique population that provides a truly unmatched opportunity to study complex diseases on a more homogeneous genetic and environmental background.

Methods : Accessing an existing research infrastructure with a 17 year history of complex disease studies, we reviewed extensive medical history questionnaires of 1,677 Amish. We reviewed ophtlamic examination records from a subset of 263. We also examined the familial structure of these indiviudals. We are currently enrolling individuals to be examined by a glaucoma specialist who will characterize the subtype of glaucoma within the Amish of Holmes County, Ohio.

Results : Self-report of prior glaucoma diagnosis was present for 144 Amish. Ophthalmic records from a subset of 263 indicated that 35 have glaucoma, 20 of whom overlap with those who self-reported glaucoma. The 35 individuals with ophthalmologist-recorded glaucoma belong to 21 sibships. Familial clustering of glaucoma is notable, as 20 of the affected individuals belong to six nuclear families ranging in size from 10-129 members.

Conclusions : We determined that heritable glaucoma is likely present in the Amish of Holmes County, Ohio. Improved, consistent phenotyping and comprehensive genetic studies are keys to understanding the complex interplay between glaucoma risk factors in order to identify disease earlier in the trajectory and identify therapeutic targets beyond the current treatments. Accessing a large Amish family to understand the genetics of heritable adult-onset glaucoma has not previously been reported, and offers the opportunity to localize novel loci as well as to, in the future, better understand the contribution of known loci. The Amish are ideal for genetic studies due to a population bottleneck created upon their immigration to the United States, resulting in a more homogeneous genetic background. Amish individuals also experience less diverse environmental exposures and thus, their non-genetic risk for glaucoma is more likely to be shared as well. Characterizing glaucoma in this group offers the potential for a great deal of insight into this high-impact complex disease.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.