Volume 6, Number 9
Monday, March 6, 2006



In this issue: (click heading to view article)
Enhanced Glaucoma Staging System for Classifying Functional Damage
Evaluation of Plasma Homocysteine and Risk of AMD
Mucin Characteristics of HCLE Cells That Exclude Rose Bengal Anionic Dye
Markers of Inflammation, Vascular Endothelial Dysfunction and Age-Related Cataract
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Enhanced Glaucoma Staging System for Classifying Functional Damage

This Italian study introduces a new method, derived from the Glaucoma Staging System (GSS), for classifying glaucomatous visual field defects. Investigators considered four sample groups composed respectively of 471 (Sample 1), 128 (Sample 2), 185 (Sample 3) and 131 (Sample 4) patients with either ocular hypertension or chronic glaucoma. The new method of classification, which the authors call GSS 2, uses the mean deviation (MD) and corrected pattern standard deviation/constant linear velocity (CPSD/CLV) or pattern standard deviation/linear velocity (PSD/LV) perimetric indices to classify visual field defect in six stages and three types (generalized, localized and mixed). The formulas were determined using Sample 1; a new borderline stage was created on the basis of Sample 2; the relationship between the PSD/LV and CPSD/CLV values was studied on Sample 3 to verify the possibility of using the uncorrected indices instead of the CPSD/CLV; and the relationship with other classification methods was studied on Sample 4.

The GSS 2 showed a strong level of association with the AGIS and the Hodapp-Parrish-Anderson methods in staging defect severity. Results also showed a good correlation with a classification based on the Bebie curve. The authors conclude that the new classification method correctly classified both damage severity and perimetric defect type in the sample studied, using either the corrected or uncorrected visual field indices. They stress that it is a quick and easy method and its formulas can be introduced in any software.

SOURCE: Brusini P, Filacorda S. Enhanced Glaucoma Staging System (GSS 2) for classifying functional damage in glaucoma. J Glaucoma 2006;15(1):40-46.
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Evaluation of Plasma Homocysteine and Risk of AMD

Homocysteine may be a modifiable risk factor for age-related macular degeneration (AMD), according to a cross-sectional case-control study by the Devers Eye Institute and the Massachusetts Eye and Ear Infirmary.

Investigators measured fasting plasma homocysteine levels at two centers in 934 individuals who were participating in an ancillary study of the Age-Related Eye Disease Study (AREDS). A total of 547 cases and 387 control subjects were determined by fundus photography. Researchers conducted conditional logistic regression analyses to assess the association of homocysteine with AMD.

Median values of homocysteine were higher among advanced AMD cases (9.51 mmol/l) compared with those who had no AMD (8.81 mmol/l). Values of greater than 12 mmol/l vs. 12 mmol/l or less were also associated with an increased risk of AMD when controlled for other covariates. The authors believe that the results are consistent with a possible small, independent association between higher homocysteine levels and AMD.

SOURCE: Seddon JM, Gensler G, Klein ML, Milton RC. Evaluation of plasma homocysteine and risk of age-related macular degeneration. Am J Ophthalmol 2006;141(1):201-3.
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Mucin Characteristics of HCLE Cells That Exclude Rose Bengal Anionic Dye

It has been proposed that mucins have a protective role, preventing rose bengal staining of normal ocular surface epithelial cells. The current study by Boston’s Schepens Eye Research Institute and Harvard Medical School evaluates rose bengal staining in a human corneal-limbal epithelial (HCLE) cell line known to produce and glycosylate membrane-associated mucins.

Researchers grew HCLE cells to confluence in serum-free medium and switched to DMEM/F12 with 10 percent serum to promote differentiation. They performed immunolocalization of the membrane-associated mucins MUC1 and MUC16 and the T-antigen carbohydrate epitope with the monoclonal antibodies HMFG-2 and OC125 and jacalin lectin, respectively. To assess dye uptake, they incubated cultures for five minutes with 0.1% rose bengal and then photographed them. To determine whether exclusion of negatively charged rose bengal requires a negative charge at the cell surface, cells were incubated with fluoresceinated cationized ferritin. The effect of hyperosmotic stress on rose bengal staining in vitro was evaluated by increasing the ion concentration (Ca(+2) and Mg(+2)) in the rose bengal uptake assay.

The cytoplasm and nucleus of confluent HCLE cells cultured in media without serum stained with rose bengal. Culture of HCLE cells in medium containing serum resulted in the formation of islands of stratified cells that excluded rose bengal. Apical cells of the stratified islands produced MUC16 and the T-antigen carbohydrate epitope on their apical surfaces. Colocalization experiments demonstrated that fluoresceinated cationized ferritin did not bind to these stratified cells, indicating that rose bengal is excluded from cells that lack negative charges. Increasing the amounts of divalent cations in the media reduced the cellular area protected against rose bengal uptake.

The results indicate that stratification and differentiation of corneal epithelial cells--measured by the capacity to produce the membrane-associated mucin MUC16 and the mucin-associated T-antigen carbohydrate on their apical surfaces--provide protection against rose bengal penetrance in vitro. They suggest a role for membrane-associated mucins and their oligosaccharides in the protection of ocular surface epithelia.

SOURCE: Argueso P, Tisdale A, Spurr-Michaud S, et al. Mucin characteristics of human corneal-limbal epithelial cells that exclude the rose bengal anionic dye. Invest Ophthalmol Vis Sci 2006;47(1):113-9.
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Markers of Inflammation, Vascular Endothelial Dysfunction and Age-Related Cataract

Two serum markers of systemic inflammation and vascular endothelial dysfunction were associated with nuclear cataract in a study by the University of Wisconsin.

The study population was a random population-based sample of 396 people aged 50 and older in Beaver Dam, WI. Investigators performed cross-sectional univariable and multivariable analyses of data and used standardized protocols for blood collection, measurement of markers, administration of a questionnaire and grading of lens photographs to determine cataract.

Interleukin-6 and intracellular adhesion molecule-1 were associated significantly with prevalent nuclear cataract (odds ratio for each quartile, 1.45 and 2.17, respectively). Many of the associations of markers with cataract types were not linear. The authors concluded that no significant associations exist between the markers and cortical or posterior subcapsular cataract.

SOURCE: Klein BE, Klein R, Lee KE, et al. Markers of inflammation, vascular endothelial dysfunction, and age-related cataract. Am J Ophthalmol 2006;141(1):116-22.
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BRIEFLY
  • MACUGEN INJECTIONS SHOW NO ADDITIONAL SAFETY CONCERNS OVER TWO YEARS. OSI Pharmaceuticals and Pfizer recently announced that Macugen, the companies’ treatment for neovascular age-related macular degeneration (wet AMD) did not increase the risk of cardiovascular problems over two years of use, according to study data. Macugen"s systemic safety profile, established in the first year of the study, was maintained over two years of treatment with no evidence of an association with hypertension, excessive bleeding or blood clots. Preliminary data suggests that the safety of Macugen is also maintained over a third year of treatment.
  • ACCUTOME INTRODUCES NEW LIMBAL RELAXING INCISION KIT. Accutome, Inc., has introduced the new Rubenstein Limbal Relaxing Incision Kit, consisting of the Rubenstein LRI pre-set diamond knife, the new Accutome LRI marker, a Fine/Thorton fixation ring, sterilization tray and marking pens. The Rubenstein LRI diamond knife is designed with a winged footplate for better control, better visualization and reduced epi drag. The high-quality natural diamond is fully retractable. The kit’s LRI marker is available in 6-mm and 8-mm chord lengths (Gills) or 40, 60 or 80 degrees (Nichamin). The company is featuring a pre-ASCRS sale. For more information, go to www.accutome.com.
  • ALCON RECEIVES POSITIVE OPINION FROM CHMP FOR DUOTRAV SOLUTION. The Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion on the initial marketing authorization for DuoTrav solution (travoprost 0.004%/timolol 0.5%). One daily drop of DuoTrav solution lowers intraocular pressure (IOP), a primary risk factor for glaucoma, by combining a beta-blocker (timolol) to decrease the production of aqueous humor with a prostaglandin analogue (travoprost) to increase the outflow of aqueous humor. The combination increases convenience for patients currently taking more than one glaucoma medication. CHMP approval sets the stage for marketing authorization of DuoTrav solution in the European Union to decrease IOP in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to topical beta-blockers or prostaglandin analogues. The marketing authorization is expected to be finalized in the second quarter of 2006. DuoTrav is approved in Australia and is under review in other countries.


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