Increased Iris Pigmentation Research Articles

α-Methyl-p-Tyrosine Inhibits Latanoprost-Induced Melanogenesis In Vitro

The PGF2α derivative, latanoprost, is a recent anti-glaucoma drug that has been reported to induce a discrete incidence of increased iris pigmentation in men. The present experiments were made in order to study whether this phenomenon could be influenced by the tyrosinase inhibitor, α-methyl-p-tyrosine. Melanin content, melanin production and tyrosinase activity of cultured uveal melanocytes derived from irides of brown or brown-blue color were measured after adding latanoprost at different molar concentration with or without α-methyl-p-tyrosine (10−5m). It was shown that latanoprost stimulated melanin content, melanin production and tyrosinase activity in a molar range between 10−7and 10−5min uveal melanocytes derived from irides of both brown and brown-blue color. The effect seemed to be more pronounced in melanocytes derived from irides of brown-blue color. The adding of α-methyl-p-tyrosine completely prevented latanoprost-induced stimulation of melanin production in uveal melanocytes derived from irides of both colors. These results suggest that latanoprost-induced stimulation of melanin production, follows the metabolic pathway involving tyrosinase activity and may be relevant for the therapeutic application of latanoprost in glaucoma in order to reduce its side-effect resulting in increased iris pigmentation.

Prostaglandin analogues in the treatment of glaucoma.

Prostaglandin (PG) analogues are a new class of ocular hypotensive drugs that have been developed for the treatment of open angle glaucoma. Two of these drugs, latanoprost and unoprostone, are presently commercially available. Latanoprost was introduced in 1996 in the US and Europe. Presently it enjoys the most widespread use and is the most well documented drug of this group. It reduces the intraocular pressure (IOP) by a mechanism of action different from other drugs; namely by increasing the uveoscleral outflow. The aqueous inflow is not affected. The optimal dose regimen is one drop of 50 microg/ml once daily, which reduces the IOP by approximately 30% in patients with glaucoma. A more pronounced ocular hypotensive effect is demonstrated when latanoprost is combined with other glaucoma therapies, including beta-blockers, adrenergic and cholinergic agonists or carbonic anhydrase inhibitors. Latanoprost is well tolerated. The drug reaches a plasma concentration below that needed for stimulation of the FP-receptor, which may explain its favourable systemic tolerability profile. The major ocular adverse effect is increased iris pigmentation, which is due to increased synthesis of melanin in the melanocytes of the iris stroma. It is most frequently seen in green-brown eyes and it is probably permanent. A low frequency of cystoid macular oedema has also been reported, predominantly in predisposed eyes. Unoprostone was launched in Japan in 1994, but there is little experience with this drug outside the Japanese market and the documentation is more limited. Its main mechanism of action is on outflow, but this is not yet fully elucidated. The recommended dosage regimen is 1 drop of 1.2 mg/ml twice daily. No comparative studies in humans between the 2 drugs have yet been published.

Latanoprost in the treatment of glaucoma and ocular hypertension.

Latanoprost (Xalatan) is a prostaglandin F(2alpha) analog prodrug which is activated when hydrolyzed in the cornea and plasma. Latanoprost reduces the intraocular pressure (IOP) by increasing uveoscleral outflow. Other locally applied medications reduce IOP either by increasing the outflow of fluid through the trabecular drainage system or by reducing the production of fluid in the eye. Latanoprost, which is used topically in the eye at the low dose of 0.005% once daily, has been shown in phase III studies carried out in Scandinavia, the U.K. and the U.S. to be capable of lowering the IOP in patients with open-angle glaucoma and ocular hypertension by 35%. This low IOP is maintained over at least a 2-year period. Latanaprost is as effective, or possible slightly more effective than timolol in its pressure reducing effects. Additional pressure reduction can be achieved by adding latanoprost to existing glaucoma medications. Because latanoprost is rapidly metabolized outside the eye, systemic side effects do not occur. Increased iris pigmentation occurs in at least 10% of hazel (but not blue or dark-eyed patients). So far no ocular problem has occurred because of the increased production of pigment which is not released from the iris. Isolated cases of cystoid macular edema have occurred, so that anyone complaining of reduction of vision while using the drug should be fully investigated.

Latanoprost treatment for glaucoma: effects of treating for 1 year and of switching from timolol

PURPOSETo determine the efficacy and safety of latanoprost treatment for 1 year in glaucoma patients, and to evaluate the effects of switching from timolol to latanoprost therapy.METHODSLatanoprost 0.005% was topically applied once daily without masking for 6 months in 223 patients with elevated intraocular pressure after previous treatment with latanoprost once daily or 0.5% timolol twice daily for 6 months in a multicenter, randomized, double-masked, parallel group study.RESULTSCompared with baseline values before treatment, a significant (P < .0001) diurnal reduction in intraocular pressure of 6 to 8 mm Hg was maintained with minimal fluctuation for the duration of treatment. When treatment was switched from timolol to latanoprost, intraocular pressure was reduced by 1.5 ± 0.3 mm Hg (mean ± SEM; 8% change in intraocular pressure; 31% of the intraocular pressure reduction produced by timolol; P < .001) compared with the change in intraocular pressure in patients remaining on latanoprost therapy. Of the patients initially enrolled, 95% successfully completed treatment. There was a slight overall increase in conjunctival hyperemia in patients who switched from timolol to latanoprost, but no change in those who continued latanoprost. The timolol-induced reduction of resting heart rate returned to baseline levels after switching to latanoprost. Of the 247 patients treated with latanoprost during the masked and/or open-label studies, 12 (5%) demonstrated a definite (n = 4) or possible (n = 8) increase in iris pigmentation.CONCLUSIONSLatanoprost is a well-tolerated ocular hypotensive agent that appears to be more effective than timolol in reducing intraocular pressure. The increase in iris pigmentation appears to be harmless but requires further investigation.

Latanoprost: Two years' experience of its use in the United Kingdom

The aim of the study was to assess the efficacy and safety of latanoprost in the long-term treatment of glaucoma. The study was designed as a randomized, 6-month double-masked parallel group, multicenter study comparing latanoprost with timolol followed by an 18-month open-label, multicenter study in which all patients were treated with latanoprost. In total, 277 patients were treated with latanoprost for up to 24 months. For the first 6 months of treatment, latanoprost (0.005%) administered once daily was compared with timolol (0.5%) administered twice daily. Patients then received latanoprost (once daily) for an 18-month follow-up period regardless of their initial treatment. Intraocular pressure (IOP) was measured over the 24-month treatment period, and any ocular-systemic symptoms or adverse events were evaluated. Latanoprost significantly reduced (P < 0.001) IOP by approximately 8 mmHg from pretreatment values, and this reduction was maintained over the 24-month treatment period with no sign of upward drift. Latanoprost is apparently free of any systemic side effect. The most significant ocular side effect with latanoprost was an increase in iris pigmentation, which occurred in 51 patients. Latanoprost, administered once daily, is effective and well tolerated for the long-term treatment of patients with open-angle glaucoma or ocular hypertension.

A double masked comparison of the intraocular pressure reducing effect of latanoprost 0.005% and 0.001% administered once daily in open angle glaucoma and ocular hypertension

AIMTo compare the intraocular pressure (IOP) reducing effect of latanoprost 0.005% and 0.001%.METHODSTwenty four patients with glaucoma or ocular hypertension were randomised into two groups. Twelve patients (group 1) were...

The color of the human eye: A review of morphologic correlates and of some conditions that affect iridial pigmentation

Iris color can be affected by a variety of ocular disorders. It is suspected that iris color may not remain constant throughout life. These observations have drawn attention to the morphologic correlates of iris color and its regulation. Differences in the iris color of normal eyes are the result of variable amounts of melanin pigment granules within a constant number of melanocytes in the superficial stroma of the iris. These melanocytes seem to reach their genetically determined amount of melanin in early childhood, and their melanin content usually remains constant in adulthood. Diseases such as Horner's syndrome and Fuchs' heterochromic iridocyclitis affect iris color, resulting in a decrease of iris pigmentation. Evidence suggests that melanin content of some melanocytes is subject to adrenergic regulation even past childhood. Application of the prostaglandin analogue latanoprost, on the other hand, leads to an increase in iris pigmentation in some patients. Studies with cultured dermal and uveal melanocytes, as well as with uveal melanoma cells, however, show no increase in cell proliferation when treated with latanoprost in vitro. The mechanisms by which latanoprost affects regulation of iris pigmentation requires further investigation.

Latanoprost, a Prostaglandin Analog, for Glaucoma Therapy: Efficacy and Safety after 1 Year of Treatment in 198 Patients

To determine efficacy and safety of latanoprost, a prostaglandin analog for glaucoma, during 1 year of treatment. After baseline measurements, 0.005% latanoprost was topically applied once daily for 12 months in patients from Scandinavia, the United Kingdom, and the United States who had elevated intraocular pressure (IOP). Diagnoses included ocular hypertension, chronic open-angle glaucoma, exfoliation syndrome, and pigment dispersion syndrome. Treatment was masked for the first 6 months and open-label during the second 6 months. Of the 272 patients initially enrolled, withdrawals were due to inadequate IOP control (1%), increased iris pigmentation (5%), other ocular problems (3%), systemic medical problems (3%), and nonmedical reasons (14%). Latanoprost significantly (P < 0.0001) reduced diumal IOP from 25.3 +/- 3.0 mmHg (mean +/- standard deviation) at baseline to 17.4 +/- 2.7 mmHg (32% reduction) at 12 months in the 198 patients who completed 1 year of treatment. The IOP reduction was maintained at a consistent level throughout the 12 months without evidence of drift, and was not affected by sex, age, race, or eye color. Overall, latanoprost caused a possible or definite increase in iris pigmentation in 12% of the 272 patients, all of whom had multicolored irides at baseline. One half of these patients with increased pigmentation withdrew before completing 1 year of therapy. Visual field, optic disc cupping, visual acuity, refractive error, conjunctival hyperemia, aqueous flare, anterior chamber cellular response, lens examination, blood pressure, heart rate, blood tests, and urinalysis were not appreciably altered. Latanoprost safely and effectively reduces IOP for 1 year in patients of diverse nationalities, providing further evidence for its usefulness in chronic glaucoma therapy.

Latanoprost. A review of its pharmacological properties, clinical efficacy and tolerability in the management of primary open-angle glaucoma and ocular hypertension.

Latanoprost is an ester prodrug analogue of prostaglandin F2 alpha which effectively reduces intraocular pressure (IOP) by increasing uveoscleral outflow rather than altering conventional trabeculo-canalicular) aqueous outflow. The IOP-lowering effect of latanoprost lasts for 20 to 24 hours after a single dose, which allows a single daily dosage regimen. Data from 4 randomised double-masked multicentre studies indicate that a once daily dose of topical latanoprost 0.005% is as effective as timolol 0.5% twice daily in the treatment of patients with primary open-angle glaucoma or ocular hypertension. A number of studies also demonstrate that latanoprost enhances IOP-lowering effects when applied in combination with other antiglaucoma agents. Latanoprost is well tolerated with no, or barely detectable, conjunctival hyperaemia, and, unlike timolol, is not associated with systemic adverse effects. However, 3 to 10% of patients treated with latanoprost 0.005% have shown increased iris pigmentation after 3 to 4.5 months' treatment. In summary, the available data show that latanoprost is a potent IOP-lowering agent with a number of positive features including a single daily dosage regimen, a novel mechanism of action that enhances the IOP-lowering effect of contemporary agents, and a lack of systemic adverse effects. These properties suitably poise latanoprost for a prominent position in the management of patients with primary open-angle glaucoma and ocular hypertension.