S.J. McKinnon

Latanoprost and brimonidine: therapeutic and physiologic assessment before and after oral nonsteroidal anti-inflammatory therapy.

PURPOSE To assess, before and during oral nonsteroidal anti-inflammatory drug coadministration, latanoprosts and brimonidines hypotensive action in eyes at risk of glaucomatous progression, assessing the effect of each drug on ocular perfusion and visual function. METHODS Twenty consenting adults with open-angle glaucoma or ocular hypertension underwent a double-masked, bilateral, randomized prospective study. Treatment started with either latanoprost 0.005% in the morning and placebo in the evening, or brimonidine 0.2% twice daily in one eye; after 1 week starting the other in the fellow eye. After another week, oral indomethacin 25 mg four times a day, commenced for 2 more weeks. Intraocular pressure, ocular circulation, and visual function were monitored pretreatment, after unilateral monotherapy (day 7), bilateral ocular therapy (day 14), and coadministered oral indomethacin (day 28). Intrasubject differences (interocular and intraocular relative to baseline) were determined by two-tailed paired t test. RESULTS A loss of the significance of intraocular pressure reduction with brimonidine was noted after oral indomethacin coadministration (-14%; P =.004 for brimonidine alone versus -11%; P =.3 with indomethacin). Significant intraocular pressure reduction with latanoprost persisted despite indomethacin (-25%; P <.0001 for latanoprost alone versus -30%; P <.0001 with indomethacin). Pulsatile ocular blood flow increased 40% with latanoprost, but was unchanged with brimonidine (interdrug difference, P =.004). Midperipheral retinal microcirculation increased 23% (P =.03) with latanoprost. Humphrey perimetry and contrast sensitivity remained consistently at or above baseline with both latanoprost and brimonidine. Indomethacin had no significant effect on ocular perfusion or visual function measures. CONCLUSIONS Circulatory and hydrodynamic findings differed substantially for the two drugs. The loss of significance of intraocular pressure reduction with brimonidine during indomethacin treatment may be clinically important.

Alpha-fodrin is cleaved by caspase-3 in a chronic ocular hypertensive (COH) rat model of glaucoma

PURPOSE alpha-Fodrin is a neuronal cytoskeletal protein and a known caspase-3 target. We sought to determine whether caspase-3 cleaves alpha-fodrin in COH rat retinas and whether this process is reduced by adeno-associated virus (AAV)-induced retinal ganglion cell expression of baculovirus inhibitory repeat-containing 4 (BIRC4), a potent caspase-3 inhibitor. METHODS Ocular hypertension was induced unilaterally in five rat eyes by limbal injection of hypertonic saline. In a similar experiment, ocular hypertension was induced in four eyes pre-treated with an intravitreal injection of AAV-BIRC4 to assess alpha-fodrin cleavage. Western immunoblotting was performed on all retinas. RESULTS Caspase-3 cleavage of alpha-fodrin yields a specific 120kDa protein fragment. COH retina immunoblots indicated significantly more caspase-3 cleavage of alpha-fodrin than controls (P < 0.01, paired t-test). Inhibition of retinal caspase-3 activity with BIRC4 reduced caspase-3-mediated alpha-fodrin cleavage compared to controls. CONCLUSIONS This confirms our previous finding of caspase-3 cleavage of alpha-fodrin in COH retinas and parallels pathology seen in Alzheimers disease, in which neurons undergo chronic caspase activation, slow build-up of cleavage products, and delayed apoptosis. If caspase activation in glaucoma leads to protracted rather than rapid retinal ganglion cell apoptosis, a much longer therapeutic window exists for apoptosis inhibition with caspase inhibitors such as BIRC4.

Echographic Diagnosis of Scleral Fold in Hypotony

PURPOSE To report the echographic appearance of a scleral fold in hypotony. METHOD We performed ultrasonography on a patient who, after trabeculectomy with mitomycin C, had an intraocular pressure of 1 mm Hg, an opaque cataract, and suspected hypotonous maculopathy in the left eye. RESULTS An area of dome-shaped eyewall thickening was noted near the tendon of the lateral rectus muscle in primary gaze. This thickening increased substantially in lateral gaze, mimicking a foreign body or a tumor. CONCLUSION Recognizing this abnormality is important to avoid erroneous diagnosis of an intraocular foreign body or a tumor in hypotonous eyes.