Henry Marshall1, Nicholas Andrew2, Emmanuelle Souzeau1, Bronwyn Ridge1, Jude Fitzgerald1, Mona Awadalla1, Anna Galanopoulos2, Kathryn Burdon3,4, Paul Healey5, Ashish Agar6, Stuart Graham7, Alex Hewitt4, John Landers1, Robert Casson2, Jamie Craig1

Purpose: To investigate whether clinical or struc- tural parameters influence whether an individual demonstrates earliest glaucomatous structural pro- gression on peripapillary retinal nerve fibre layer (pRNFL) or macular ganglion cell-inner plexiform layer (mGCIPL). Design: Prospective longitudinal cohort study. Participants: 271 eyes from 207 individuals with definite glaucomatous progression on optical coher- ence tomography (OCT)-Guided Progression Analy- sis TM(GPA) software were drawn from a total of 1271 eyes from 686 individuals categorized as glau- coma suspect or early manifest glaucoma undergo- ing glaucoma surveillance.
Methods: Individuals demonstrating earliest longi- tudinal progression on mGCIPL GPA event analysis were compared to individuals demonstrating earli- est longitudinal progression on pRNFL GPA event analysis.
Outcome Measures: Correlation of OCT event change analysis with Intra-ocular Pressure (IOP) and baseline thickness of the pRNFL and mGCIPL. Results: Eyes demonstrating earliest longitudinal progression on mGCIPL had significantly maximum-recorded pre-treatment IOP (P < 0.001), mean IOP (P < 0.001) and minimum IOP (P = 0.004). The time interval between progression on pRNFL and progression on mGCIPL increased by 1.06 years for every 5mmHg increase in IOP. Eyes demonstrating earliest longitudinal progres- sion on mGCIPL had a significantly lower baseline average pRNFL thickness (P < 0.001). The ability to predict pRNFL or mGCIPL first progression was optimized by combining baseline average pRNFL thickness with maximum-recorded pre-treatment IOP (AUC: 0.771; 95%CI: 0.684-0.857). Individuals with a maximum-recorded pre-treatment IOP ≥22.0 mmHg and baseline thickness ≥80.5um were 3.6 times more likely to progress on pRNFL-first than mGCIPL-first (PPV 78.9%). Conclusion: maximum-recorded pre-treatment IOP and baseline average pRNFL thickness influence whether an individual demonstrates structural pro- gression first on mGCIPL or pRNFL.