latanoprost and Iris-Diseases

Topics: Administration, Topical; Aged; Amides; Bimatoprost; Cloprostenol; Cysts; Dinoprost; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Iris Diseases; Latanoprost; Pigment Epithelium of Eye; Prostaglandins F, Synthetic; Recurrence; Retreatment

The new glaucoma drugs latanoprost, isopropyl unoprostone, travoprost, and bimatoprost cause increased pigmentation of the iris in some patients. The purpose of the present article is to survey the available preclinical and clinical data on prostaglandin-induced iris pigmentation and to assess the phenomenon from a clinical perspective. Most of the data have been obtained with latanoprost, and it appears that there is a predisposition to latanoprost-induced iris pigmentation in individuals with hazel or heterochromic eye color. As latanoprost and travoprost are selective agonists for the prostaglandin F(2alpha) receptor, it is likely that the phenomenon is mediated by this receptor. Several studies indicate that latanoprost stimulates melanogenesis in iridial melanocytes, and transcription of the tyrosinase gene is upregulated. The safety aspects of latanoprost-induced iris pigmentation have been addressed in histopathologic studies, and no evidence of harmful consequences of the side effect has been found. Although a final assessment of the clinical significance of prostaglandin-induced iris pigmentation currently is impossible to make, it appears that the only clear-cut disadvantage is a potential heterochromia between the eyes in unilaterally treated patients because the heterochromia is likely to be permanent, or very slowly reversible.

Topics: Amides; Animals; Antihypertensive Agents; Bimatoprost; Cloprostenol; Dinoprost; Eye Color; Gene Expression Regulation; Humans; Iris; Iris Diseases; Latanoprost; Lipids; Melanocytes; Monophenol Monooxygenase; Pigmentation Disorders; Prostaglandins F, Synthetic; Receptors, Prostaglandin; Travoprost; Up-Regulation

Latanoprost therapy can lead to iris darkening in susceptible individuals, particularly those with hazel eyes. Concerns have been raised about whether latanoprost, and for that matter other prostanoids, may have a harmful effect on the iris. In addition, it is unknown whether latanoprost causes increased pigmentation of the outflow pathways that might eventually lead to blockage and a type of pigmentary glaucoma. The present study summarizes findings from the authors' own laboratories on the effects of latanoprost as seen by light and electron microscopy of the iris and outflow tissues and reviews the as yet limited, relevant literature. The findings support the proposal that latanoprost-induced eye color change is likely to be due to an increased amount of melanin within iris stromal melanocytes rather than any increase in melanocyte numbers, although many aspects of the darkening process remain obscure. No marked pathological changes were found in the latanoprost-treated iris; however, the numbers of specimens examined by us to date are still small (40 specimens in all) and those with latanoprost-induced darkening are even fewer (18). In the authors' experience, pigmentation of the outflow system in latanoprost-treated eyes was no greater than in eyes with primary open-angle glaucoma without prostanoid treatment, but there have been only limited numbers of trabeculectomy specimens examined. Concerns about latanoprost producing meshwork hyperpigmentation and pigmentary glaucoma are discussed.

Topics: Antihypertensive Agents; Eye Color; Glaucoma; Humans; Intraocular Pressure; Iris; Iris Diseases; Latanoprost; Melanins; Melanocytes; Pigmentation Disorders; Prostaglandins F, Synthetic; Trabecular Meshwork

To evaluate the comparative efficacy and tolerance of latanoprost versus timolol through a meta-analysis of randomised controlled trials (RCTs).. Systematic retrieval of RCTs of latanoprost versus timolol to allow pooling of results from head to head comparison studies. Quality of trials was assessed based on randomisation, masking, and withdrawal. Sensitivity analyses were used to estimate the effects of quality of study on outcomes. The data sources were Medline, Embase, Scientific Citation Index, Merck Glaucoma, and Pharmacia and Upjohn ophthalmology databases. There were 1256 patients with open angle glaucoma or ocular hypertension reported in 11 trials of latanoprost versus timolol. The main outcome measures were (i) percentage intraocular pressure (IOP) reduction for efficacy; (ii) relative risk, risk difference, and number needed to harm for side effects such as hyperaemia, conjunctivitis, increased pigmentation, hypotension, and bradycardia expressed as dichotomous outcomes; and (iii) reduction in systemic blood pressure and heart rate as side effects.. Both 0.005% latanoprost once daily and 0.5% timolol twice daily reduced IOP. The percentage reductions in IOP from baseline (mean (SE)) produced by latanoprost and timolol were 30.2 (2.3) and 26.9 (3.4) at 3 months. The difference in IOP reduction between the two treatments were 5.0 (95% confidence intervals 2.8, 7.3). However, latanoprost caused iris pigmentation in more patients than timolol (relative risk = 8.01, 95% confidence intervals 1.87, 34.30). The 2 year risk with latanoprost reached 18% (51/277). Hyperaemia was also more often observed with latanoprost (relative risk =2.20, 95% confidence intervals 1.33, 3.64). Timolol caused a significant reduction in heart rate of 4 beats/minute (95% confidence interval 2, 6).. This meta-analysis suggests that latanoprost is more effective than timolol in lowering IOP. However, it often causes iris pigmentation. While current evidence suggests that this pigmentation is benign, careful lifetime evaluation of patients is still justified.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Confidence Intervals; Cross-Over Studies; Double-Blind Method; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Iris Diseases; Latanoprost; Male; Middle Aged; Ocular Hypertension; Pigmentation Disorders; Prostaglandins F, Synthetic; Randomized Controlled Trials as Topic; Risk Factors; Single-Blind Method; Timolol; Treatment Outcome

This introductory overview considers the advantages of a class of local hormones-the prostaglandins (PGs)-for the management of intraocular pressure (IOP) in glaucoma, over agonists and antagonists of neurotransmitters that dominated this field in the 20th century. PGs and PG analogues, in particular esterified prodrug forms of PGF2 alpha, are effective ocular hypotensive agents, but cause some conjunctival hyperemia and corneal sensory irritation at higher concentrations. Based on structure-activity studies, a 17-phenyl PGF2 alpha prodrug, latanoprost (PhXA41), was found to have a greatly improved therapeutic index, without compromising the ocular hypotensive potency of PGF2 alpha prodrugs. The IOP lowering mechanism of such PGF2 alpha s, increased uveoscleral outflow, can be expected to have great physiologic advantages, especially with respect to normal tension glaucoma, over most currently used ocular hypotensive drugs. The introduction of this new approach has already led to a new insight into the control and clinical significance of this outflow route. Similarly, the newly discovered ocular side effect, PG-induced increase in iridial pigmentation, can be expected to provide insight into the oculo-protective role of iridial melanocytes and into the punative association between a decline in the ocular melanin system and the vulnerability of the eye to some age-related diseases.

Topics: Animals; Eye Color; Glaucoma; Humans; Intraocular Pressure; Iris Diseases; Latanoprost; Melanosis; Prostaglandins F, Synthetic

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.

Topics: Cell Count; Cell Division; Eye Color; Humans; Iris; Iris Diseases; Latanoprost; Melanins; Pigment Epithelium of Eye; Pigmentation Disorders; Prostaglandins F, Synthetic

To compare incidence of iridial pigmentation prospectively induced by long term treatment with latanoprost and isopropyl unoprostone (hereafter, unoprostone) in Japanese patients with glaucoma.. Patients with glaucoma treated with prostaglandin (PG) related ophthalmic solutions were sequentially enrolled. Patients treated for more than 30 months with PG related ophthalmic solutions were subjected to analysis. The entry criteria were no history of intraocular surgery, laser iridotomy, and/or laser trabeculoplasty within 12 months before and after the enrolment; and no history of uveitis; no changes in antiglaucoma drugs within 6 months before and after the enrolment. Photographs of the irides were taken under the same conditions and three glaucoma specialists evaluated the iridial pigmentation with masking of patient information. The correlation of iridial pigmentation with the background factors and the reduction of intraocular pressure (IOP) before and after the treatment were investigated.. 48 eyes in 48 patients satisfied the enrolment criteria (25 eyes in the latanoprost group, 23 eyes in the unoprostone group). At the end of the follow up period, iridial pigmentation was present in 15 patients (60.0%) in the latanoprost group and seven patients (30.4%) in the unoprostone group. The correlation between development of iridial pigmentation and age, sex, concurrent use of other ophthalmic solutions, and IOP reduction was not significant.. The incidence of iridial pigmentation induced by latanoprost or unoprostone is high in the case of long term treatment. Iridial pigmentation did not affect PG related ophthalmic solution induced IOP reduction.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Dinoprost; Eye Color; Female; Follow-Up Studies; Glaucoma; Humans; Iris Diseases; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Pigmentation Disorders; Prospective Studies; Prostaglandins F, Synthetic; Risk Factors

To investigate the incidence of iridial pigmentation induced by latanoprost ophthalmic solution in Japanese glaucoma patients by a prospective and observer-masked study.. Sixty-nine eyes of 69 glaucoma patients were included. Patients who had undergone intraocular surgery, laser trabeculoplasty, and laser iridotomy within 12 months before enrollment, and patients with history of uveitis and any changes in antiglaucoma drugs within 6 months before enrollment were excluded. Iridial photographs were taken by one examiner under the same conditions at 1, 3, and 6 months after the initiation of latanoprost treatment. Three glaucoma specialists, masked of patient information, independently assessed the iridial pigmentation. Cases with iridial pigmentation diagnosed by three specialists were categorized as showing a definite increase in iridial pigmentation.. A definite increase in iridial pigmentation occurred in 3.5%, 9.7%, and 35.0% of eyes within 1, 3, and 6 months of treatment, respectively. Age, gender, or concomitantly used eyedrops did not significantly influence the incidence of iridial pigmentation within 6 months of instillation. A reduction of intraocular pressure by latanoprost did not differ significantly between patients with and without iridial pigmentation.. The incidence of iridial pigmentation by latanoprost ophthalmic solution in Japanese patients was higher than previously reported values in pigmented races.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Eye Color; Female; Glaucoma; Humans; Incidence; Intraocular Pressure; Iris; Iris Diseases; Japan; Latanoprost; Male; Melanosis; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins F, Synthetic

To compare the efficacy and side effects and the effect on aqueous humor dynamics of 0.005% latanoprost applied topically once daily with 0.5% timolol given twice daily for 12 months to patients with pigmentary glaucoma.. Prospective, randomized, double-masked, clinical study.. Thirty-six patients affected with bilateral pigmentary glaucoma controlled with no more than a single hypotensive medication were enrolled in the study.. The sample population was randomly divided into 2 age- and gender-matched groups each of 18 patients. Group 1 received 0.005% latanoprost eyedrops once daily and the vehicle (placebo) once daily; group 2 was assigned to timolol 0.5% eyedrops twice daily.. Diurnal curves of intraocular pressure (IOP) were performed on the baseline day and after 0.5, 3, 6, and 12 months of treatment. The IOP measurements were performed at 8:00 AM, 12:00 noon, 4:00 PM, and 8:00 PM. Outflow facility ("C") was measured on the baseline day and on the last day of the study with a Schiotz electronic tonometer. A two-tailed Student's t test for paired or unpaired data was used for statistical evaluation of differences between treatment and baseline values or between the latanoprost and timolol group. Diurnal IOP measurements were compared hour by hour. Mean values of the two eyes IOP and "C" were used for analysis.. Compared with baseline measurements, both latanoprost and timolol caused a significant (P < 0.001) reduction of IOP at each hour of diurnal curve throughout the duration of therapy. Reduction of IOP was 6.0 +/- 4.5 and 5.9 +/- 4.6 with latanoprost and 4.8 +/- 3.0 and 4.6 +/- 3.1 with timolol after 6 and 12 months, respectively. Comparison of mean diurnal measurements with latanoprost and timolol showed a statistical significant (P < 0.001) difference at 3, 6, and 12 months. Mean "C" was found to be significantly enhanced (+30%) only in the latanoprost-treated group compared with the baseline (P = 0.017). Mean conjunctival hyperemia was graded at 0.3 in latanoprost-treated eyes and 0.2 in timolol-treated eyes. A remarkable change in iris color was observed in both eyes of 1 of the 18 patients treated with latanoprost and none of the 18 patients who received timolol. Darkening of the peripheral iris stroma was suspected in two patients treated with latanoprost. In the timolol group, heart rate was significantly reduced from 72 +/- 9 at baseline to 67 +/- 10 beats per minute at 12 months.. Although further studies may need to confirm these data on a larger sample and to evaluate the side effect of increased iris pigmentation on long-term follow-up, in patients with pigmentary glaucoma, 0.005% latanoprost taken once daily was well tolerated and more effective in reducing IOP than 0.5% timolol taken twice daily.

Topics: Administration, Topical; Adult; Aqueous Humor; Double-Blind Method; Drug Administration Schedule; Female; Glaucoma, Open-Angle; Heart Rate; Humans; Intraocular Pressure; Iris Diseases; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Pigmentation Disorders; Prospective Studies; Prostaglandins F, Synthetic; Timolol

Topics: Aged; Cataract Extraction; Eye Color; Female; Humans; Intraocular Pressure; Iris; Iris Diseases; Latanoprost; Ocular Hypertension; Ophthalmic Solutions; Pigmentation Disorders; Prostaglandins F, Synthetic

Latanoprost, a phenyl-substituted analogue of prostaglandin F2 alpha administered as eye drops, induces increased melanogenesis in the iridial melanocytes of monkeys. Similar effects were seen in 12, 23 and 11% of patients in the USA, United Kingdom (UK) and Scandinavia, respectively, during one year of treatment. The highest incidence of induced pigmentation was seen in green-brown, yellow-brown and blue/grey-brown eyes, in that order. The relatively high proportion of patients with green-brown eyes in the UK explains the larger number of affected patients in this country. Typically, a concentric increase of the iris pigmentation appeared after six months (range: 3-17) and was judged to be noticeable by the patient in about 2/3 of the cases. After cessation of latanoprost, no change of the induced pigmentation has been seen in patients followed for two years, and there have been no signs of dispersion of pigment into the anterior chamber. Irides, homogeneously blue, grey, green or brown, were seldom affected. Naevi or freckles on iris, conjunctiva, or eye lids were not affected. It is intriguing that many patients with mixed eye color, particularly the blue-brown eyes, have not developed increased pigmentation even during two years of treatment. This could be due to a relatively slow melanogenesis or to refractory melanocytes in these individuals.

Topics: Adrenergic beta-Antagonists; Double-Blind Method; Europe; Eye Color; Glaucoma; Humans; Incidence; Intraocular Pressure; Iris; Iris Diseases; Latanoprost; Melanins; Melanosis; Ophthalmic Solutions; Prostaglandins F, Synthetic; Time Factors; Timolol; United States

To compare the intraocular pressure (IOP)-reducing effect and side effects of 0.005% latanoprost administered once daily with 0.5% timolol administered twice daily in patients with open-angle glaucoma or ocular hypertension.. This was a randomized, double-masked study with two parallel groups and a treatment period of 6 months. The primary objective of the study is to compare the IOP-reducing effect of lantanoprost with that of timolol at the end of the 6-month treatment period. A total of 294 patients were included: 149 were in the latanoprost group and 145 were in timolol group. Latanoprost was administered in the evening.. Diurnal IOP (9:00 am, 1:00 pm, 5:00 pm) was reduced from 25.2 to 16.7 mmHg (33.7%) with lantanoprost and from 25.4 to 17.1 mmHg (32.7%) with timolol as determined at the end of the 6-month treatment period. No upward drift in IOP occurred with either drug during the treatment period. Latanoprost caused a somewhat more conjunctival hyperemia than timolol and more corneal punctuate epithelial erosions. However, both drugs were generally well tolerated. The most significant side effect of latanoprost was increased pigmentation of the iris which was observed in 15 patients (10.1%). Timolol caused more systemic side effects than latanoprost.. Latanoprost 0.005% administered once daily in the evening reduced IOP at least as well as timolol 0.5% administered twice daily. Latanoprost was generally well tolerated systemically and in the eye. However, the drug has an unusual side effect of increasing the pigmentation of the iris, particularly in individuals with green-brown or blue-brown eyes.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Double-Blind Method; Drug Administration Schedule; Female; Glaucoma, Open-Angle; Hemodynamics; Humans; Intraocular Pressure; Iris Diseases; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Pigmentation Disorders; Prostaglandins F, Synthetic; Timolol; Visual Acuity

Latanoprost, a new prostaglandin analogue, was compared with timolol for ocular hypotensive efficacy and side effects.. In a multicenter, randomized, double-masked, parallel group study, 268 patients with ocular hypertension or early primary open-angle glaucoma received either 0.005% latanoprost once daily or 0.5% timolol twice daily for 6 months. All except ten patients from each group successfully completed the study.. Intraocular pressure (IOP) was significantly (P<0.001) reduced and maintained by both medications without evidence of a long-term drift over 6 months. Comparing 6-month with baseline diurnal IOP values, the IOP reduction (mean +/- standard deviation) achieved with latanoprost (-6.7 +/- 3.4 mmHg) was significantly (P<0.001) greater than that produced with timolol (4.9 +/- 2.9 mmHg). Four patients treated with timolol and none treated with latanoprost were withdrawn from the study because of inadequate IOP control. Pulse rate was significantly reduced with timolol, but not with latanoprost. Slightly more conjunctival hyperemia appeared in latanoprost-treated compared with timolol-treated eyes. Fewer subjective side effects occurred in latanoprost-treated eyes. Both eyes of a patient with a characteristic, concentric iris heterochromia (darker centrally) at baseline showed a definite, photographically documented increase in pigmentation during latanoprost treatment, making the irides uniformly darker. Three additional patients treated with latanoprost were suspects for this color change. Otherwise, no significant difference between treatment groups occurred visual acuity, slit-lamp examination, blood pressure, and laboratory values.. Latanoprost has the potential for becoming a new first-line treatment for glaucoma.

Topics: Adrenergic beta-Antagonists; Adult; Aged; Aged, 80 and over; Conjunctiva; Double-Blind Method; Drug Administration Schedule; Female; Glaucoma, Open-Angle; Hemodynamics; Humans; Hyperemia; Intraocular Pressure; Iris Diseases; Latanoprost; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Pigmentation Disorders; Prostaglandins F, Synthetic; Timolol; United States

A 25-year-old man presented with decreased vision in both eyes, approximately 4 years following bilateral bright ocular cosmetic iris implantation. On examination, he was found to have bilateral elevated intraocular pressures, anterior chamber cells and flare, chronic peripheral anterior synechiae and significantly reduced endothelial cell counts. Ultrasound biomicroscopy demonstrated compression of the peripheral iris, resulting in synechial angle closure in both eyes. Surgical removal of the implants was performed without additional complication. On removal, bilateral iris atrophy was evident with non-reacting pupils and permanent mydriasis. Optical coherence tomography angiography showed a reduction in iris vasculature density that is more pronounced in the area of the iris atrophic defects. This case suggests that cosmetic iris implants may compress iris vasculature, resulting in decreased iris perfusion resulting in atrophic mydriasis and iris defects. This is a potential novel mechanism for complications in eyes with cosmetic iris implants.

Topics: Acetaminophen; Acetazolamide; Administration, Intravenous; Adult; Analgesics, Non-Narcotic; Carbonic Anhydrase Inhibitors; Humans; Intraocular Pressure; Iris; Iris Diseases; Latanoprost; Male; Mydriasis; Ophthalmic Solutions; Prostheses and Implants; Tomography, Optical Coherence

A 74 year-old woman present with blurry vision of 12 hour duration in her right eye, and with no other symptoms. Biomicroscopic examination revealed a 3 mm hyphaema in her right eye and multiple nodular structures in the pupillary margin of both eyes.. Iris tufts are vascular anomalies unrelated to ischaemia that must be included in the differential diagnosis of spontaneous hyphaema.

Topics: Administration, Topical; Aged; Brimonidine Tartrate; Cyclopentolate; Dexamethasone; Diabetes Mellitus, Type 2; Female; Glaucoma, Open-Angle; Hamartoma; Humans; Hyphema; Iris Diseases; Latanoprost; Microscopy, Acoustic; Ophthalmic Solutions; Prostaglandins F, Synthetic; Quinoxalines; Vision Disorders

The only proven therapy for glaucoma is intraocular pressure (IOP) reduction, which can be accomplished by different means. Each should be properly discussed with patients in order to best preserve visual function and quality of life. We report a case of unilateral pseudoexfoliative glaucoma, treated for years with triple topical IOP-lowering drugs. The patient presented with advanced optic neuropathy and important ocular side effects secondary to the treatment. Having discussed his options and prognosis, laser trabeculoplasty was performed while maintaining the remaining therapy considering the advanced stage of glaucoma. His IOP was effectively reduced and no progression was noted after 1-year follow-up. Although medical therapy is the mainstream in glaucoma management, its side effects should not be ignored, especially in unilateral cases. Surgery might have been a better solution, but we chose to perform laser trabeculoplasty, an effective and safer alternative, considering the unlikely but serious risk of the "wipe-out phenomenon" in this case.

Topics: Antihypertensive Agents; Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Exfoliation Syndrome; Glaucoma, Open-Angle; Humans; Hypertrichosis; Intraocular Pressure; Iris Diseases; Latanoprost; Male; Middle Aged; Pigmentation Disorders; Prostaglandins F, Synthetic; Sulfonamides; Thiazines; Timolol; Trabeculectomy

Topics: Administration, Topical; Aged; Cysts; Female; Glaucoma; Humans; Iris Diseases; Latanoprost; Optic Disk; Prostaglandins F, Synthetic; Ultrasonography

Topics: Antihypertensive Agents; Eye Color; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Iridectomy; Iris; Iris Diseases; Latanoprost; Melanins; Melanocytes; Pigmentation Disorders; Prostaglandins F, Synthetic

To study the histopathological features of latanoprost-treated irides with or without darkening, compared with non-latanoprost-treated irides.. Iridectomy specimens and patient history forms were independently examined by 3 ophthalmic pathologists in a masked fashion. Specimens were evaluated for premalignant changes and for differences in level of pigmentation and degrees of cellularity, inflammation, and vascular abnormalities.. The specimens consisted of 22 latanoprost-treated darkened irides, 35 latanoprost-treated irides without darkening, and 35 non-latanoprost-treated irides. There was a statistically significant decrease in the number of nuclear invaginations and prominent nucleoli in latanoprost-treated darkened irides compared with the other 2 groups (P = .004 and P = .005, respectively). The average thickness and pigmentation of the anterior border layer was greater in the latanoprost-treated darkened irides than in the other 2 groups (P = .03 and P = .02, respectively). The latanoprost-treated darkened irides had increased pigmentation of the stroma (P < .001), stromal fibroblasts (P < .001), melanocytes (P = .005), vascular endothelium (P = .02), and adventitia (P < .001) relative to the other 2 groups.. There is no histopathological evidence of premalignant changes in latanoprost-treated darkened irides. The latanoprost-induced iris color changes are due to a thickening of the anterior border layer and an increased amount of melanin in the anterior border layer and within the stromal melanocytes.

Topics: Antihypertensive Agents; Endothelium, Vascular; Fibroblasts; Glaucoma; Humans; Iridectomy; Iris; Iris Diseases; Latanoprost; Melanins; Melanocytes; Melanosis; Prostaglandins F, Synthetic

To investigate the morphological and melanin granule changes in irides after variable-term exposure to latanoprost, where the latanoprost-induced iris darkening (LIID) side effect has been identified and photographically recorded.. Experimental study.. Fifteen LIID cases and 15 untreated controls.. Iridectomy specimens from LIID cases were collected from patients undergoing trabeculectomy, whereas before surgery they had been on topical latanoprost and there was clear evidence of iris color change from the treating ophthalmologist, which was recorded photographically. A control series of peripheral iridectomies were obtained from blue, heterogeneous, and brown irides. All the specimens were visualized by light and electron microscopy. Masked assessment was made of stromal cell number, cell atypia, anterior border thickness, presence of free stromal melanin, melanin proximity to blood vessels, and change in stromal melanocyte melanin granule numbers and size. For the melanin granule analysis, electron micrographs were subjected to detailed image analysis to quantify the number of melanin granules, size of the granules, and overall percentage filling of the iris stromal melanocytes with melanin.. Iris morphology and melanin granule changes.. There was no evident difference in stromal cellularity or anterior border thickness. Atypia, free stromal melanin, and melanin adjacent to blood vessel lumina were identified, but there was no difference between LIIDs and controls. Within stromal melanocytes, we found no change in the total number of melanin granules of the LIID cases, as compared with the brown and heterogeneously colored normals. However, melanin granules in the anterior border melanocytes of the LIID eyes were significantly larger than those in the controls. A trend towards bigger melanin granules was apparent in the deep stroma, but this difference did not reach significance.. In the LIID cases that we examined, the darkening side effect does not seem to be associated with either proliferative or generative iris changes, nor with increases in number of granules. Instead, it appears to be due to small increases in the size of mature melanin granules, particularly in the anterior border region.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Eye Color; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Iridectomy; Iris; Iris Diseases; Latanoprost; Male; Melanins; Melanocytes; Middle Aged; Pigmentation Disorders; Prostaglandins F, Synthetic

The aim of this study was to provide numerical evidence that latanoprost induced iris darkening (LIID) can be caused by changes to the melanin granule size distribution in the anterior segment of the iris. Iridectomies from two patients were used, where both had undergone unilateral treatment with latanoprost and had exhibited LIID. The untreated eye provided the comparative control. Micrographs from the iris samples were analysed to determine the number and size of the mature melanin granules. Monte Carlo (MC) simulation of light propagation in the iris was performed to examine the changes in reflectance and absorption with varying particle size and density. The reflected intensity of light was obtained as a function of wavelength. CIE colour theory was employed in order to estimate a perceived colour from the reflectance data. MC simulations showed that the reflectance was reduced for the LIID irises compared to the control irises for both subjects and for all wavelengths of light. The MC simulated colours were in good agreement with the in vivo photography of the eye colour. Hence, we have demonstrated that increases in melanin granule size causes iris darkening, and can explain LIID.

Topics: Antihypertensive Agents; Computer Simulation; Dose-Response Relationship, Drug; Eye Color; Humans; Iris; Iris Diseases; Latanoprost; Melanins; Models, Biological; Monte Carlo Method; Pigmentation Disorders; Prostaglandins F, Synthetic

The purpose of the present study was to investigate the incidence and severity of iridial pigmentation under latanoprost topical use on brown eyes in Taiwan.. Retrospective review study was conducted from April 1999 to October 2001 in the Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan, for glaucoma clinic monthly follow-up patients; 140 open-angle glaucoma patients on 0.005% latanoprost were enrolled. Analyses of iridial pigmentation incidence, grading, patient age distribution, side effect, and time course were performed. Boys-Smith pigment gradation lens was used as standard for semiquantitative iris pigmentation grading.. Before 0.005% latanoprost use, 90% of the patients enrolled were noted with iridial pigmentation grade I, and 10% were with grade I-II, but not reaching grade II scale standard. A total of 60 patients on 0.005% latanoprost developed increased pigmentation of the iris during the follow-up period. An increase of iris pigmentation was noted after an average of 7.27 months use of latanoprost (range 1-19 months, SD 2.65 months). For iridial pigmentation grading, 57.1, 30.7, 10.0, and 2.1% of our patients were noted to have grade I, II, III, and IV respectively. Most patients with latanoprost-induced iris hyperpigmentation were with grade II iridial pigmentation. There were 15 patients (10.7%) (10 female and five male) with hypertrichosis in the study group who were not compatible with the iridial pigmentation status. Among these patients, female patients had higher incidence of hypertrichosis than males, but this did not bother them. Only four patients (2.8%) were with conjunctiva chemosis and three patients (2.1%) with lid margin hyperpigmentation.. Contrary to the belief that latanoprost rarely caused iris hyperpigmentation in yellow-brown eyes, our study showed that 42.8% iris hyperpigmentation did occur, especially after continual use for around 7 months. Higher hyperpigmentation incidence were noted in male than in female patients. This might be due to stronger adrenergic incidence in male than in female patients. Although hypertrichosis and increasing eyelid pigmentation together with iridial pigmentation represented a potentially permanent cosmetic side effect, they are very rare and occurred in no more than 3% in our patients. It is a good way to take Boys-Smith pigment gradation lens for iridial pigmentation grading and for long-term continual evaluation. The doctors should exert great care in differentiating drug-induced iris pigmentation and iris nevi from early stage uveal melanoma.

Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Antihypertensive Agents; Child; Female; Glaucoma, Open-Angle; Humans; Hyperpigmentation; Hypertrichosis; Iris Diseases; Latanoprost; Male; Middle Aged; Prostaglandins F, Synthetic; Retrospective Studies; Severity of Illness Index

This study aimed to determine whether the longterm use of latanoprost is associated with an increase in trabecular pigmentation, especially in subjects in whom iris pigmentation has increased.. We enrolled 50 subjects for whom treatment was to start for ocular hypertension, primary open-angle glaucoma or normal tension glaucoma. All subjects received latanoprost 0.005% daily. Trabecular pigmentation was documented using gonioscopic photography of the inferior quadrant at baseline, every 3 months for the first year and every 6 months for the second and third years. Three glaucoma specialists evaluated the series of gonioscopic photographs for each eye of each subject in a masked fashion. The intraocular pressure (IOP) was also recorded at each visit.. A total of 41 subjects (79 eyes) completed 3 years of follow-up, and none showed any increase in the grade of trabecular pigmentation, including 10 subjects (20 eyes) in whom the iridial pigment increased.. Although latanoprost increased iridial pigmentation in some subjects, we found no evidence of an increase in trabecular pigmentation over the 3 years of follow-up.

Topics: Antihypertensive Agents; Glaucoma, Open-Angle; Gonioscopy; Humans; Hyperpigmentation; Intraocular Pressure; Iris Diseases; Latanoprost; Middle Aged; Ocular Hypertension; Photography; Prostaglandins F, Synthetic; Trabecular Meshwork

To study the histologic aspects of irises subjected to extended latanoprost treatment.. Prospective, observer-masked study.. Iris biopsies of eyes treated with latanoprost were analyzed (all had a photographically documented increase in iris pigmentation) plus control eyes (untreated with prostanoids) using optical microscopy. PATIENT OR STUDY POPULATION: There were 14 study eyes treated with latanoprost and 8 untreated control eyes.. The morphologic characteristics of the irises.. The irises treated with latanoprost had an increased number of melanocytes with nuclear inclusions, granules of melanin in the vascular walls and the melanocytes and free granules in the stroma compared with control eyes (P = .001, P = .01, P = .004, P = .01, respectively, by the chi(2) test).. Chronic therapy with latanoprost appears to induce more changes in the iris than a simple increase in the melanin content of the melanocytes.

Topics: Aged; Antihypertensive Agents; Biopsy; Exfoliation Syndrome; Eye Color; Female; Glaucoma, Open-Angle; Humans; Inclusion Bodies; Iris; Iris Diseases; Latanoprost; Male; Melanins; Melanocytes; Melanosis; Middle Aged; Prospective Studies; Prostaglandins F, Synthetic

Topics: Aged; Antihypertensive Agents; Cysts; Female; Glaucoma, Angle-Closure; Humans; Intraocular Pressure; Iris Diseases; Latanoprost; Photography; Pigment Epithelium of Eye; Prostaglandins F, Synthetic

To report an ocular side effect of topical latanoprost therapy.. Single interventional case report.. A 73-year-old woman on latanoprost for primary open-angle glaucoma developed an iris cyst simulating an iris melanoma.. The lesion disappeared over 8 weeks when latanoprost was stopped.. In managing patients with iris-pigmented lesions, the list of medications should be reviewed. If the patient takes latanoprost, a trial off latanoprost is warranted.

Topics: Aged; Antihypertensive Agents; Cysts; Diagnosis, Differential; Female; Glaucoma, Open-Angle; Humans; Iris Diseases; Iris Neoplasms; Latanoprost; Melanoma; Prostaglandins F, Synthetic

Topics: Antihypertensive Agents; Cysts; Diagnosis, Differential; Glaucoma, Open-Angle; Humans; Iris Diseases; Iris Neoplasms; Latanoprost; Melanoma; Prostaglandins F, Synthetic

This microscopic study was undertaken to compare the melanocytes of peripheral iridectomy specimens from two eyes that had latanoprost-induced iris darkening (LIID) with iridectomies taken from the fellow untreated eyes.. The two patients in this study were the ones who underwent LIID in the latanoprost treated eye from a series of 17 patients requiring bilateral trabeculectomy. The first trabeculectomy procedure provided a control peripheral iridectomy for each patient, whereas the second eye was treated with once daily 50 microg ml(-1) latanoprost drops for 6 months. The four peripheral iridectomy specimens from the two LIID patients were subjected to quantitative morphometric analysis by light microscopy of iris cellularity, and electron microscopy of iris melanocyte immature melanosomes and mature melanin granules.. There was no significant difference in stromal cellularity between the LIIDs and their respective controls nor were there significant differences in the numbers of immature melanosomes or melanin granules in the melanocytes. However, there was a significant increase in the diameter of melanin granules that was more pronounced in the anterior border layer than the deeper stroma. With the anterior border melanocytes, the increase in melanin granule size was associated with significant increases in granule area and the percentage of cell cytoplasm occupied by melanin (granularity).. The only morphological change identified in two peripheral iridectomies that had LIID when compared to untreated fellow eye specimens was a modest increase in the size of stromal melanocyte melanin granules that was more pronounced in the cells of the anterior border region.

Topics: Antihypertensive Agents; Exfoliation Syndrome; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Iridectomy; Iris; Iris Diseases; Latanoprost; Melanins; Melanocytes; Melanosomes; Microscopy, Electron; Pigmentation Disorders; Prostaglandins F, Synthetic; Stromal Cells; Trabeculectomy

To report on new software that was specially designed to evaluate color.. Software development and observational case report. Each pixel on a computer screen is composed of three colors: red, green, and blue (RGB). Our software analyzes the intensity of each RGB component in a specific area chosen by the user. To test our software, we evaluated the color level of the irises of a subject, which became darker as a side effect of Xalatan (latanoprost; Pharmacia Corporation, Peapack, New Jersey) eyedrops.. We successfully expressed the level of the color of the iris by number.. This software measures the color of a lesion and thereby provides an objective evaluation of color. The software we developed is downloadable, without cost, from http://www.isao.com.

Topics: Antihypertensive Agents; Eye Color; Humans; Iris; Iris Diseases; Latanoprost; Pigmentation Disorders; Prostaglandins F, Synthetic; Software Design

To report the histopathologic and immunohistochemical findings from the iridectomy specimen of a patient with acquired unilateral iris heterochromia due to latanoprost.. A 45-year-old woman with open-angle glaucoma and unilateral iris heterochromia was evaluated for uncontrolled intraocular pressure increase. Subsequently, the patient underwent trabeculectomy with mitomycin C and an iridectomy specimen was obtained for analysis.. The histopathologic analysis of the iridectomy specimen did not reveal any nuclear atypia, nuclear crowding, or mitotic figures. Immunohistochemical studies showed that the iris melanocytes were negative for HMB45 and S-100, and weakly positive for Melan A.. Latanoprost-associated iris color change may exhibit a diffuse, uniform, dark velvet-brown appearance, thereby simulating diffuse iris melanoma. Histopathologic and immunohistochemical analysis confirmed the benign characteristics of the affected iris melanocytes.

Topics: Antihypertensive Agents; Diagnosis, Differential; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Iris; Iris Diseases; Latanoprost; Melanosis; Middle Aged; Mitomycin; Prostaglandins F, Synthetic; Trabeculectomy

To determine the effect on iris color of discontinuing latanoprost (LP) treatment in a patient with pronounced iris color darkening, and to assess the possible role of sympathetic innervation.. In a patient demonstrating pronounced iris color darkening in both eyes after treatment with LP for 6 months, magnified iris color photographs were taken at 3- to 6-month intervals for 5 years after discontinuation of LP treatment. Pupillary testing for sympathetic insufficiency was performed with cocaine 10% or hydroxyamphetamine 1%.. The iris color did not appreciably change after discontinuing LP. The cocaine-induced increase in pupillary diameter was considerably greater for the control subject than for the patient who demonstrated the LP-induced color change.. Latanoprost-induced iris color darkening does not appreciably change for several years after discontinuing treatment. Some eyes that show LP-induced darkening may have relative ocular sympathetic insufficiency.

Topics: Antihypertensive Agents; Autonomic Nervous System Diseases; Cocaine; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Iris; Iris Diseases; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Pigmentation Disorders; Prostaglandins F, Synthetic; Pupil; Sympathetic Nervous System

Latanoprost, the active principle of Xalatan eye drops, is a prostaglandin F2alpha analogue in widespread use for the treatment of glaucoma. During chronic treatment with the drug, an increased pigmentation of the iris was observed in both primates and man. To gain an insight into the nature of this effect, we analyzed the stroma of the irides of cynomolgus monkeys subjected to 25-38 weeks of treatment. A highly sensitive procedure, based on chemical degradation by alkaline hydrogen peroxide oxidation, or hydriodic acid hydrolysis, was developed, which allowed eumelanin and pheomelanin analysis of a single iris at a time. Untreated monkey irides were found to be essentially pheomelanic, providing further support to the recently reported occurrence of these pigments in human irides. In the Latanoprost-treated eyes, the amount of eumelanin increased from three to sevenfold, while the variation of pheomelanin did not exceed 25%. The increase in eumelanin/pheomelanin ratio in the treated eyes, as compared with the contralateral control eyes, varied from three to fivefold, and the change was statistically significant (P < 0.01; t-test). Based on the results of parallel studies, showing that Latanoprost does not induce proliferation of iridial melanocytes, and that the other pigmented layers of the iris which do not contain melanocytes are not affected by the drug, it can be concluded that the observed effect is a result of a direct interaction with the melanogenic mechanism. This probably involves activation of tyrosinase, as suggested, to account for the stimulation of melanin synthesis by related compounds, including natural prostaglandins.

Topics: Administration, Topical; Animals; Antihypertensive Agents; Female; Hyperpigmentation; Iris; Iris Diseases; Latanoprost; Macaca fascicularis; Melanins; Melanocytes; Monophenol Monooxygenase; Ophthalmic Solutions; Prostaglandins F, Synthetic

To report an adverse side effect associated with topical latanoprost usage.. Case report. A 76-year-old woman with primary open-angle glaucoma developed an iris cyst 5 weeks after beginning treatment with latanoprost. Clinical examinations and slit-lamp photographs were performed.. Latanoprost was discontinued. Periodic examinations disclosed that the iris cyst gradually diminished and finally disappeared within 3 weeks.. The formation of an iris cyst is a possible complication of topical latanoprost therapy.

Topics: Administration, Topical; Aged; Cysts; Female; Glaucoma, Open-Angle; Humans; Iris Diseases; Latanoprost; Ophthalmic Solutions; Prostaglandins F, Synthetic; Visual Acuity

Topics: Aged; Eye Color; Female; Humans; Intraocular Pressure; Iris; Iris Diseases; Latanoprost; Ocular Hypertension; Pigmentation Disorders; Prostaglandins F, Synthetic

Topics: Eye Color; Glaucoma; Humans; Infant; Intraocular Pressure; Iris Diseases; Latanoprost; Male; Ophthalmic Solutions; Pigmentation Disorders; Prostaglandins F, Synthetic; Sturge-Weber Syndrome

Latanoprost, a new ocular hypotensive prostaglandin F2 alpha analogue prodrug, was found to induce increased pigmentation of monkey irides in chronic toxicity studies. This prompted us to investigate the effect of naturally occurring prostaglandins on the monkey iris to determine whether this pigmentary effect is unique for latanoprost or whether it is a class effect of prostaglandins. PGF2 alpha-isopropyl ester (IE), PGE2-IE and latanoprost were applied topically to cynomolgus monkey eyes for 18-44 weeks. One eye of each animal was treated, while the other served as control. In addition, latanoprost was applied to sympathectomized monkey eyes. PGF2 alpha-IE, PGE2-IE, as well as latanoprost, induced increased pigmentation in the monkey eye. The first signs of this effect were seen after about two months of treatment. Latanoprost also induced increased pigmentation in sympathectomized eyes. It is concluded that both naturally occurring prostaglandins and their synthetic analogues can induce increased iridial pigmentation in cynomolgus monkeys, and that the effect does not require the presence of sympathetic nerves.

Topics: Administration, Topical; Animals; Dinoprost; Dinoprostone; Eye Color; Iris; Iris Diseases; Latanoprost; Macaca fascicularis; Melanosis; Ophthalmic Solutions; Pigment Epithelium of Eye; Prostaglandins; Prostaglandins F, Synthetic; Sympathectomy