Lachlan S. W. Knight, Jonathan B. Ruddle, Deepa A. Taranath, Ivan Goldberg, James E. Smith, Glen Gole8, Mark Y. Chiang9, Faren Willett, Guy D'Mellow, James Breen, Ayub Qassim, Sean Mullany, James E. Elder, Andrea L. Vincent, Sandra E. Staffieri, Lisa S. Kearns, David A. Mackey,, Susie Luu, Owen M. Siggs, Emmanuelle Souzeau,Jamie E. Craig

Purpose: To report the relative frequencies of childhood and early-onset glaucoma subtypes and their genetic findings in a large single cohort.

Methods: Referrals of individuals with childhood glaucoma (diagnosed 0 to <18 years) and early-onset glaucoma (diagnosed 18 to <40 years) recruited to the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG) over a 14-year period (2007-2021) were respectively reviewed. Glaucoma subtypes were deter- mined using the Childhood Glaucoma Research Network classifications. DNA extracted from blood or saliva samples underwent sequencing of genes associated with glaucoma. Results: Three hundred individuals with childhood glaucoma and 392 individuals with early-onset glaucoma were referred to the ANZRAG. Primary glaucomas were most prevalent in either cohort (childhood: 226/300, 75.3%; early-onset: 288/392, 73.5%). Genetic testing in pro-bands resulted in a diagnostic yield of 26.4% (137/518) and reclassification of glaucoma subtype in 9.5% of pro- bands (13/137). The highest molecular diagnostic rate was achieved in probands with glaucoma associated with non-acquired ocular anomalies (57.1%). Pathogenic variants in 20 genes were found. Biallelic variants inCYP1B1 (n = 32; 6.2%) and heterozygous variants inMYOC (n = 25; 4.8%) and FOXC1 (n = 21; 4.1%) were most commonly reported amongst pro-bands. Biallelic CYP1B1 variants were more commonly reported in females (61.5% vs 38.5%; p = 0.03). Conclusion: We report on the largest cohort of individuals with childhood and early-onset glaucoma from Australasia using the Childhood Glaucoma Research Network classification. Primary glaucomas were most prevalent. Genetic diagnoses ascertained in 26.4% of pro- bands supported clinical diagnoses and genetic counsel- ling. International collaborative efforts to characterise genetic associations in rare phenotypes will improve genetic diagnostic rates and management of these glaucomas.