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S. D. Grozdanic, H. Kecova, M. M. Harper, W. Nilaweera, M. Kuehn, R. H. Kardon; Cholinergic Drug Induced Reversal of Early Functional Deficits in Glaucoma. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2784.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize early functional, structural and molecular changes in a canine model of hereditary primary glaucoma and response to an indirect cholinergic agent (demecarium bromide-DB) that may have neuroprotective effects.
Intraocular pressure (IOP) was evaluated with tonometry. The function of the retina was evaluated using electroretinography (scotopic, photopic, multifocal and pattern ERG). Thickness of the nerve fiber layer was evaluated using optical coherence tomography (OCT). Topical DB 0.3% was applied once daily for 3 months.
Gradual increase in IOP was observed with an increase in age: 8m = 14 mmHg (median value), 15m = 15.5 mmHg, 18 m = 17.5 mmHg, 20 m = 24 mmHg, and 30 months = 36 mmHg. OCT analysis in glaucomatous dogs showed significant thickening of the nerve fiber layer (NFL) in superior and nasal quadrants (p=0.005 and p=0.03 respectively, Student’s t-test) in dogs with early glaucoma (IOP<20 mmHg). ISCEV and multifocal ERG did not reveal significant retinal deficits, however pattern ERG analysis showed significantly reduced amplitudes in glaucomatous dogs (gla = 3.5+0.4 µV; ctrl = 6.2+0.3 µV; p=0.0004, Student’s t-test) in early stages of glaucoma. There was a significant correlation between IOP and pERG deficits (r2=0.87, p<0.0001). Posterior bowing of lamina cribrosa (without NFL loss) was the earliest structural change in early glaucoma eyes. Topical demecarium bromide did not have significant effect on IOP (p>0.5, Paired t-test), however pERG amplitudes significantly improved in treated dogs (before = 3.6+0.3 µV; post = 4+0.4 µV; p=0.004, Paired t-test).
The early changes in glaucomatous canine eyes are characterized by structural (NFL thickening) and dysfunctional retinal ganglion cell changes (pERG deficits), most likely due to gradual increase in intraocular pressure and structural changes at the lamina cribrosa region. Functional optic nerve deficits were significantly reversed with the use of this topical cholinergic drug, independent of its effect on intraocular pressure.
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