Dr. Ron’s Research Review – August 24, 2011

This week’s research review focuses on glaucoma and HRT, cortisol and melatonin.

Studies performed on women taken hormone replacement therapy showed significant decreases in intraocular pressure and significant increases in tear break-up time and Schirmer test scores, which were due to estrogen. (Ozcura and Aydin 2007)

One of the most significant complications of steroid (cortisone) use is corticosteroid-induced glaucoma, which is characterized by an increase in intraocular pressure. Five percent of the population are high steroid responders and develop an intraocular pressure (IOP) elevation of more than 15 mm Hg above baseline. (Razeghinejad and Katz 2011)

Melatonin may be a novel neuroprotectant that may be useful for the treatment of glaucoma. Melatonin protects ocular tissues by effectively scavenging free radicals and excessive amounts of NO generated in glaucoma. (Belforte, Moreno et al. 2010) (Rosenstein, Pandi-Perumal et al. 2010)

Dr. Ron


Articles

Topical estrogen drops may be a new alternative in the treatment of glaucoma

            (Ozcura and Aydin 2007) Download

Steroid-Induced Iatrogenic Glaucoma

            (Razeghinejad and Katz 2011) Download

Steroids in susceptible individuals can cause a clinical condition similar to primary open-angle glaucoma. Five percent of the population are high steroid responders and develop an intraocular pressure (IOP) elevation of more than 15 mm Hg above baseline. IOP elevation may occur as early as 1 day to as late as 12 weeks after intravitreal triamcinolone in 20-65% of patients. On average, 75% of eyes with steroid implants require IOP-lowering therapy at some point within 3 years of follow-up. The exact mechanism of steroid-induced glaucoma is not totally understood, but decreased trabecular meshwork outflow is regarded as the main cause of IOP elevation. High-risk patients who receive steroids should be monitored closely and if they develop elevated IOP, steroids with lower potency or steroid-sparing agents should be used. The IOP usually returns to normal within 2-4 weeks after stopping the steroid. About 1-5% of patients do not respond to medical therapy and need surgery. Trabeculectomy, trabeculotomy, shunt surgery, and cyclodestructive procedures are among the methods employed. Removal of residual sub-Tenon or intravitreal steroids may help hasten the resolution of the steroid response. Early results with anecortave acetate, an analog of cortisol acetate with antiangiogenic activity, in controlling IOP have been promising.

Melatonin: a novel neuroprotectant for the treatment of glaucoma

            (Belforte, Moreno et al. 2010) Download

Glaucoma is a leading cause of blindness. Although ocular hypertension is the most important risk factor, several concomitant factors such as elevation of glutamate and decrease in gamma-aminobutyric acid (GABA) levels, disorganized NO metabolism, and oxidative damage could significantly contribute to the neurodegeneration. The aim of this report was to analyze the effect of melatonin on retinal glutamate clearance, GABA concentrations, NO synthesis, and retinal redox status, as well as on functional and histological alterations provoked by chronic ocular hypertension induced by intracameral injections of hyaluronic acid (HA) in the rat eye. In normal retinas, melatonin increased glutamate uptake, glutamine synthase activity, GABA turnover rate, glutamic acid decarboxylase activity, superoxide dismutase activity, and reduced glutathione (GSH) levels, whereas it decreased NOS activity, L-arginine uptake, and lipid peroxidation. To assess the effect of melatonin on glaucomatous neuropathy, weekly injections of HA were performed in the eye anterior chamber. A pellet of melatonin was implanted subcutaneously 24 hr before the first injection or after six weekly injections of HA. Melatonin, which did not affect intraocular pressure (IOP), prevented and reversed the effect of ocular hypertension on retinal function (assessed by electroretinography) and diminished the vulnerability of retinal ganglion cells to the deleterious effects of ocular hypertension. These results indicate that melatonin could be a promissory resource in the management of glaucoma.

Melatonin as a therapeutic tool in ophthalmology: implications for glaucoma and uveitis

            (Rosenstein, Pandi-Perumal et al. 2010) Download

Several lines of evidence support the view that increased free radical generation and altered nitric oxide (NO) metabolism play a role in the pathogenesis of highly prevalent ocular diseases, such as glaucoma and uveitis. Data are discussed indicating that melatonin, being an efficient antioxidant that displays antinitridergic properties, has a promising role in the treatment of these ocular dysfunctions. Melatonin synthesis occurs in the eye of most species, and melatonin receptors are localized in different ocular structures. In view of the fact that melatonin lacks significant adverse collateral effects even at high doses, the application of melatonin could potentially protect ocular tissues by effectively scavenging free radicals and excessive amounts of NO generated in the glaucomatous or uveitic eye.


References

Belforte, N. A., M. C. Moreno, et al. (2010). "Melatonin: a novel neuroprotectant for the treatment of glaucoma." J Pineal Res 48(4): 353-64.

Ozcura, F. and S. Aydin (2007). "Topical estrogen drops may be a new alternative in the treatment of glaucoma." Med Hypotheses 69(2): 456.

Razeghinejad, M. R. and L. J. Katz (2011). "Steroid-Induced Iatrogenic Glaucoma." Ophthalmic Res 47(2): 66-80.

Rosenstein, R. E., S. R. Pandi-Perumal, et al. (2010). "Melatonin as a therapeutic tool in ophthalmology: implications for glaucoma and uveitis." J Pineal Res 49(1): 1-13.