Michael Motolko

Comparison of allergy rates in glaucoma patients receiving brimonidine 0.2% monotherapy versus fixed-combination brimonidine 0.2%–timolol 0.5% therapy

ABSTRACT Objective: To evaluate the incidence of ocular allergy in glaucoma patients prospectively treated with 0.2% brimonidine–0.5% timolol fixed combination (Combigan*) compared with the incidence of ocular allergy in patients treated with 0.2% brimonidine (Alphagan‡) monotherapy. † Combigan and ‡Alphagan are registered trade names of Allergan Inc, Irvine, CA, USA Study design and methods: This was a comparative, non-randomized, single-site, interventional study involving patients with primary open-angle glaucoma or exfoliation syndrome who had not previously used brimonidine in any formulation and had no history of ocular allergy. In one study arm, 102 patients were prospectively treated with twice-daily 0.2% brimonidine–0.5% timolol fixed combination. In the other study arm, medical charts at the same center were reviewed to identify a control group of 102 patients who had been treated with twice-daily 0.2% brimonidine monotherapy. Follow-up was at 1, 3, 6, 9, 12, 15, and 18 months of treatment. Main outcome measure: Ocular allergy defined as the presence of follicles and redness severe enough to warrant discontinuation of the medication. Results: The incidence of ocular allergy over 18 months of treatment was 8.8% (9/102) in the fixed-combination group compared with 17.6% (18/102) in the brimonidine group ( p = 0.097). Kaplan–Meier survival analysis suggested that ocular allergy may be reduced or delayed in patients treated with the brimonidine–timolol fixed combination ( p = 0.066). Conclusions: The brimonidine–timolol fixed combination was associated with a 50% lower incidence in ocular allergy compared with 0.2% brimonidine monotherapy. This difference between treatments was not statistically significant ( p = 0.097) but is likely to be clinically important. Additional studies are needed to evaluate the incidence of ocular allergy associated with brimonidine–timolol fixed combination treatment.

Contrast sensitivity in asymmetric glaucoma

We measured central contrast sensitivity in both eyes of 27 patients with asymmetric glaucomatous visual field loss or optic disc cupping. In 15 patients contrast sensitivity was less in the eye that by perimetry or ophthalmoscopy was the more severely damaged. In 10 patients contrast sensitivity was the same in the two eyes. In two patients, it was impaired more in the eye with the normal visual field. However, the latter two patients had ophthalmoscopic evidence of optic nerve damage (disc hemorrhage or large cup) in the eye with the lower contrast sensitivity, even though the visual field was normal. Asymmetry of contrast sensitivity was not found in normal control subjects.These results suggest that glaucoma does alter central vision, even when visual acuity remains normal and visual field defects are far from fixation. Contrast sensitivity may be impaired by a different mechanism than that which leads to visual dield loss. Although the two types of visual dysfunction often occur together, some patients may have more severe impairment of central vision (as measured by contrast sensitivity testing) in one eye and more severe loss of peripheral vision (as measured by perimetry) in the other eye.

Effect of Healon and Viscoat on outflow facility in human cadaver eyes

PURPOSE To compare the acute effects of Healon (sodium hyaluronate) and Viscoat (sodium chondroitin sulfate-sodium hyaluronate) on outflow facility in human cadaver eyes and determine which viscoelastic agent is least likely to cause an intraocular pressure (IOP) spike after cataract surgery. SETTING The Glaucoma Research Lab, University of Toronto, Ontario, Canada. METHODS In this prospective paired study, 15 pairs of human cadaver eyes were used. Following the construction of a 3.0 mm scleral tunnel, 0.25 cc of Healon was injected into the anterior chamber of 1 eye and 0.25 cc of Viscoat was injected into the contralateral eye. The viscoelastic agents were removed from both eyes in a standardized fashion and the scleral tunnels closed. The eyes were then perfused at a constant IOP of 8.0 mm Hg, corresponding to 16.0 mm Hg in vivo. Outflow facility (microL/minute [min]/mm Hg) was recorded every 15 minutes for 24 hours using standard methods. RESULTS Outflow facility in the Viscoat-treated eyes decreased appreciably for the first 3 hours, then recovered somewhat after 12 hours; facility in the Healon-treated eyes showed less of an overall decrease. Over the 24 hour perfusion period, mean outflow facility was 0.037 microL/min/mm Hg +/- 0.015 (SD) in the Viscoat-treated eyes and 0.060 +/- 0.012 microL/min/mm Hg in the Healon-treated eyes. Healon reduced outflow facility significantly less than Viscoat between 3.25 and 10.50 hours postoperatively (P < .05, 2-tailed t test). CONCLUSIONS Healon reduced outflow facility less than Viscoat between 3.25 and 10.50 hours postoperatively.

TGF-β induces phosphorylation of phosphatase and tensin homolog: implications for fibrosis of the trabecular meshwork tissue in glaucoma

Fundamental cell signaling mechanisms that regulate dynamic remodeling of the extracellular matrix (ECM) in mechanically loaded tissues are not yet clearly understood. Trabecular meshwork (TM) tissue in the eye is under constant mechanical stress and continuous remodeling of ECM is crucial to maintain normal aqueous humor drainage and intraocular pressure (IOP). However, excessive ECM remodeling can cause fibrosis of the TM as in primary open-angle glaucoma (POAG) patients, and is characterized by increased resistance to aqueous humor drainage, elevated IOP, optic nerve degeneration and blindness. Increased levels of active transforming growth factor-β2 (TGF-β2) in the aqueous humor is the main cause of fibrosis of TM in POAG patients. Herein, we report a novel finding that, in TM cells, TGF-β-induced increase in collagen expression is associated with phosphorylation of phosphatase and tensin homolog (PTEN) at residues Ser380/Thr382/383. Exogenous overexpression of a mutated form of PTEN with enhanced phosphatase activity prevented the TGF-β-induced collagen expression by TM cells. We propose that rapid alteration of PTEN activity through changes in its phosphorylation status could uniquely regulate the continuous remodeling of ECM in the normal TM. Modulating PTEN activity may have high therapeutic potential to alleviating the fibrosis of TM in POAG patients.