Purpose
To compare the effect of experimental glaucoma (EG) and optic nerve transection (ONT) on optic nerve head (ONH) basal blood flow (BF) differentiating BF changes induced by chronic elevated IOP from non-IOP associated optic neuronal degeneration.
Methods
In adult NHPs, unilateral ONT (n=5) and chronic IOP elevation (n=15) were induced surgically and by trabecular meshwork laser, respectively.. The contralateral eye served as control (CTL). Baseline (BL) ONH BF measurements at IOP 10 mmHg (excluding large vessels) was measured by Laser Speckle Flowgraphy (n=3-5 times). RNFLT was measured by SDOCT at BL and bi-weekly post-laser or ONT. ONH BF measurements for both eyes were split in groups based on RNFLT loss (percentage vs. BL): 1) BL, 2) <10%, 3) 10% to 20%, 4) 20% to 30%, 5) 30% to 40%, and 6) > 40%. A repeated measure ANOVA and post hoc Fisher’s LSD test assessed ONH BF change (EG vs CTL, and ONT vs CTL).
Results
ONT eyes developed a linear decrease in BF that correlated strongly with RNFLT loss (R2 = 0.9), and achieved significance once RNFLT loss was >10% (Fisher’s LSD).EG eye bf increased significantly compared to BL (p=0.03 *) while RNFLT loss was <10%.As RNFLT decreased further (10-30%), BF returned to being statistically indistinguishable from BL in the EG eyes and was significant different only after RNFLT loss was > 30%. There was no significant BF change in the CTL eyes at any post treatment time point (Fig.1). There was a significant interaction between stage of RNFLT and treatment in both EG (p<0.0001) and ONT (p=0.001) groups.
Conclusions
Both ONT and EG models cause RNFLT loss. However, EG chronic IOP elevation produces an early increase in BF through 10% RNFLT loss that is not present in ONT. This indicates the mechanisms underlying early ONH BF change in EG may be different than ONT. It suggests an early autoregulation dysfunction in EG and may reflect primary insults that precede and/or directly contribute to early RGC axon loss. The eventual decrease in ONH BF in EG could be contributed by neural degeneration, as evidenced in the ONT model. The mechanisms of early BF autoregulation in EG are understudy.