Characterizing and quantifying the temporal relationship between structural and functional change in glaucoma

PURPOSE: To characterize and quantify the temporal relationship between structural and functional change in glaucoma. METHODS: 120 eyes of 120 patients with ocular hypertension or primary open-angle glaucoma were selected from the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study. Patients had 11 visits, separated by at least 3 months over 5 to 10 years. Each visit had rim area (RA) and mean sensitivity (MS) measurements taken within a 30-day period. The structure-function (SF) relationship was summarized using conventional and modified cross-correlation functions (CCFs), which identified the strongest absolute and positive correlation, respectively. Patients were categorized in one of the following three groups: RA and MS evolved simultaneously (lag = 0), RA preceded MS (lag<0), and MS preceded RA (lag>0). Lagging regression analysis was used to examine the variations of the SF relationship within groups. RESULTS: The number of participants, mean visit lag, and mean correlation (standard deviation) were, for the conventional and modified CCFs, respectively: lag = 0 [16, 0, 0.53 (0.10) and 16, 0, 0.46 (0.11)]; lag<0 [50, −2.94, 0.51 (0.11) and 55, −3.45, 0.44 (0.12)], and lag>0 [54, 3.35, 0.53 (0.13) and 49, 3.78, 0.45 (0.12)]. A significant difference of the visit lag relation within groups was identified using lagging regression analysis (p<0.0001). CONCLUSIONS: The strongest relationship between structure and function was obtained at different visit lags in different patients. This finding also suggests that the SF relationship should be addressed at the subject level when using both measurements jointly to model glaucoma progression.