RJ Casson

Background:
We have previously shown thatelevated vitreal glucose levels provide robustneuroprotec-tion against acute and chronic experimental retinalischemia, and against experimental glaucoma. Recentdata indicate that the protective effect is mediatedby glycolytic energy production and reducing agentsupply via the pentose phosphate pathway. In thisearly translational study, we aimed to test the hypoth-esis that elevated vitreal glucose levels could tempo-rarily improve psychophysical parameters of visualfunction in primary open-angle glaucoma (POAG)patients.

Methods:
n a preliminary study on non-diabeticpatients scheduled for vitrectomy, we showed thatintensive topical application of glucose (50% glucose 5minutely for 1 hour) significantly elevated the vitreousglucose concentration in pseudophakic but not phakic individuals.

We then conducted a double-blind, randomizedcrossover study on 28 pseudophakic eyes of 15 patientswith POAG. The main outcome measure was changefrom baseline in contrast sensitivity (CS) at 12 cycles/degree as measured with the CSV-1000. CS at 3, 6, and18 cycles/degree, and the logarithm of the minimumangle of resolution (logMAR) visual acuity (VA) weresecondary outcomes.

Topical saline was used as a control, with a washoutinterval of 2–3 weeks. Participants randomly receivedeither glucose/saline or saline/glucose. We applied thesame glucose-dosing regimen as per the preliminarystudy, measuring CS, logMAR VA, refraction, intraocu-lar pressure (IOP), and central corneal thickness (CCT)at baseline and 15–30 minutes after drops. The effectof treatment was modeled by linear regression usinga generalized estimating equation approach to para-meter estimation.

Results:
There were no adverse effects. Saline hadnegligible effect on visual function. The mean changefrom baseline after glucose treatment on the CS at 12cycles /degree was 0.25 log units (95% C.I 0.09 -.42)greater than saline (P = 0.003). CS was also signi-ficantly enhanced compared to controls at 3, 6, and18 cycles/degree (P = < 0.000; P = 0.006; P = 0.042,respectively). The mean change in logMAR VA was2 letters (95% C.I. 0.7 -3.3) greater after glucose(P = 0.002). The glucose treatment had no significanteffect on refraction, IOP, or CCT.

Conclusions: Intensive topical glucose reached thevitreous in pseudopkakes, and improved the mean CSand visual acuity in a group of pseudophakic patientswith POAG, suggesting possible temporary neuro-recovery at the level of the retina.