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Edward Ryan Collantes, Baojian Fan, Manuel Jr. Delfin, Janey Wiggs; A prospective study of the natural history of MYOC-associated juvenile open-angle glaucoma. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1254.
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© ARVO (1962-2015); The Authors (2016-present)
Juvenile open angle glaucoma (JOAG),a primary open angle glaucoma developing before age 35,can lead to irreversible blindness if not detected and treated early.Myocilin (MYOC) mutations are known to cause JOAG.We have identified a Filipino family with JOAG due to a novel MYOC stop-loss mutation,c.1515A>G (p*505Wext*42).Examining this family over time has allowed for determining the natural history of disease related to this mutation,including important information about the onset of intraocular pressure (IOP) elevation,timing of treatment and therapeutic outcomes.
Fifty-seven members of a 4-generation family with a high prevalence of JOAG were recruited and examined.DNA samples were obtained and the MYOC gene sequenced.Segregation analysis was done and clinically unaffected mutation carriers were examined over the course of 43 months.The clinical exam included visual acuity,slit-lamp,tonometry,gonioscopy & fundus exam.
Of the 57 family members,26 were carriers of the stop loss mutation.The youngest mutation carrier was 1,the oldest was 64 years.13 mutation carriers were affected by JOAG (average age:28 years +/- 9;range:16-49) and were treated with a combination of medications and surgery.Despite treatment,11 of these mutation carriers had no light perception in at least one eye.Four mutation carriers were newly diagnosed with JOAG as part of the family ascertainment.Of the 25 mutation carriers,8 subjects did not have clinical evidence of glaucoma at the time the family was ascertained.The age range was 1 to 15 years old.They were regularly examined every 12 months for the first 2 years and then every 4 months.During this period,one subject from the unaffected mutation carriers developed high IOP at age 14.The average IOP was within the normal range for the remaining 7 subjects (12.7-17.6 mmHg).There was no significant change in the visual acuity and cup to disc ratio.
This is the first stop-loss MYOC mutation that has been described.In this family,this mutation appears to exhibit variable age of onset with 100% penetrance by age 49.The variable age of onset could suggest that other factors can modify disease development.Regular follow-up visits of mutation carriers who do not have glaucoma allows us to gather insights into the natural history of MYOC-associated JOAG.This information will be of critical importance as gene-based therapies become available in the future.
This is a 2020 ARVO Annual Meeting abstract.
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