Early Pointwise Sensitivity Fluctuation Predicts Glaucoma Progression

AimTo assess the relationship between pointwise visual field (VF) sensitivity fluctuation and localised glaucoma progression. MethodsRetrospective observational analysis of prospective cohort data from 399 participants (641 eyes) in the African Descent and Glaucoma Evaluation Study (ADAGES). Glaucoma, glaucoma suspect, and control participants underwent annual examinations including VF testing. VF fluctuation was evaluated using the pointwise standard deviation (SD) of total deviation (TD) residuals during the early 30-month period. Pointwise progression was defined independently at each location as a confirmed sensitivity loss >7 dB. The primary outcome was the association between early fluctuation and subsequent pointwise progression. We additionally evaluated whether the early pointwise rate of change (slope) strengthened this association. ResultsOf 33,332 VF points, 5.8% showed progression over 12.2 {+/-} 3.1 years. Progression occurred more frequently in glaucoma (15.6%) than in suspects (1.6%) or controls (0.4%) (p<0.0001). In glaucomatous eyes, progressive points demonstrated greater early fluctuation (median 1.75 dB; IQR 1.52-2.00) than non-progressive points (1.14 dB; IQR 0.97-1.34; p<0.0001) and faster early slopes (-0.65 vs 0.08 dB/year; p<0.0001). In multivariable mixed-effects models, higher early fluctuation ({beta} = 0.40 {+/-} 0.02; p<0.0001) and faster early slopes ({beta} = - 0.40 {+/-} 0.02; p<0.0001), but not baseline TD (p=0.92), were associated with progression. Conclusions: Greater early pointwise VF fluctuation independently predicted future localised progression. The slope analysis mirrored these findings, indicating that early functional variability reflects underlying local instability. These results support early pointwise fluctuation as a predictor of glaucoma progression and a potential endpoint for clinical trials.