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Prostaglandins: a new approach to glaucoma management with a new, intriguing side effect.

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.

Animals↗

Sun exposure and melanocytic naevi in young Australian children.

Queensland, Australia, has the highest rates of melanoma in the world and Queensland children have the greatest numbers of melanocytic naevi, the strongest risk factor for melanoma. Although both melanoma and naevi are broadly related to sun exposure in childhood, the relation to individual exposure early in life is difficult to study retrospectively in adults. We surveyed 506 children aged 1-6 years who had been born in Townsville, North Queensland. Sun exposure was assessed by questionnaire and melanocytic naevi were counted using a standard international protocol. Very high counts (upper quarter) of melanocytic naevi were significantly associated with sun exposure of more than 4 hours per day (adjusted relative risk ratio 3.29; 95% Cl 1.12-9.69), and with a history of sunburn (1.89; 1.11-3.21). Melanocytic naevus counts increased with age, light skin reflectance, and freckling. With exposure to intense ultraviolet light in Townsville, children develop melanocytic naevi early in life and in large numbers. We found that both acute and chronic exposure to sun are associated with their development.

Child↗

Randomized, double-masked, placebo-controlled comparison of the efficacy of emedastine difumarate 0.05% ophthalmic solution and ketotifen fumarate 0.025% ophthalmic solution in the human conjunctival allergen challenge model.

BACKGROUND: Emedastine difumarate 0.05% ophthalmic solution and ketotifen fumarate 0.025% ophthalmic solution are 2 topical antiallergic agents available in the United States and other countries. Emedastine is indicated for the temporary relief of the signs and symptoms of allergic conjunctivitis. Ketotifen is indicated for the temporary relief of ocular itching caused by allergic conjunctivitis. OBJECTIVE: The purpose of this study was to compare the efficacy of these agents in the temporary relief of ocular itching due to allergic conjunctivitis. The 2 agents were compared with each other and with placebo (artificial tears) using the conjunctival allergen challenge (CAC) model. METHODS: This was a single-center, randomized, double-masked, placebo-controlled study. At visit 1, CAC was performed on eligible subjects to identify the dose required to elicit a positive allergic reaction. Subjects returned after 7 days for visit 2 to confirm the allergen dose. On day 14 (+/-3) of the study, enrolled subjects were randomized to 1 of 3 treatment groups: emedastine in I eye and placebo in the other, ketotifen in 1 eye and placebo in the other, or emedastine in 1 eye and ketotifen in the other. In 25 subjects, bilateral CAC was performed 5 minutes after study medication instillation. In a second group of 20 subjects, CAC was performed 15 minutes after medication instillation. Itching was graded according to a standardized 5-point scale (0 = none to 4 = severe itching) at 3, 5, and 10 minutes postchallenge. Differences in efficacy scores between treatments and versus placebo were compared using 2-sample t tests of equal variance. RESULTS: A total of 45 patients (mean age, 41.2 years) received treatment: 16 received emedastine in 1 eye and ketotifen in the other; 14 received emedastine in 1 eye and placebo in the other; and 15 received ketotifen in 1 eye and placebo in the other. Both emedastine and ketotifen significantly inhibited itching (P < 0.05) compared with placebo at all time points after the 5- and 15-minute CAC. Mean raw scores for the active treatments were not statistically different. The mean itching efficacy scores were also not statistically different between active treatments. No adverse events were reported in this study. CONCLUSION: The results of this study suggest that emedastine and ketotifen are not significantly different with respect to anti-itching efficacy in the CAC model of acute allergic conjunctivitis.

Allergens↗

A randomized, double-blind, placebo-controlled comparison of emedastine 0.05% ophthalmic solution with loratadine 10 mg and their combination in the human conjunctival allergen challenge model.

BACKGROUND: When selecting treatment for allergic conjunctivitis, a primary concern is whether to choose local or systemic therapy. OBJECTIVE: This study compared the efficacy of topical emedastine 0.05% ophthalmic solution with that of oral loratadine 10 mg and their combination in the conjunctival allergen challenge model of allergic conjunctivitis. METHODS: This was a single-center, randomized, double-masked, placebo-controlled, parallel-group study. At visit 1, eligible subjects underwent conjunctival allergen challenge to identify the dose required to elicit a positive allergic reaction. After 7 days, subjects returned for visit 2, at which the allergen dose was confirmed. At visit 3, which took place 2 weeks later, subjects were randomized to receive either emedastine plus placebo capsules, loratadine plus placebo eyedrops, or both emedastine and loratadine. One hour after receiving study drug, subjects were challenged with allergen in both eyes. Allergic signs and symptoms were graded using standardized 5-point scales. The primary efficacy variables were itching and conjunctival hyperemia. Secondary efficacy variables were ciliary and episcleral hyperemia, chemosis, lid swelling, and tearing. Itching was graded subjectively at 3, 5, and 10 minutes after challenge. All other variables were assessed at 5, 10, and 20 minutes after challenge. RESULTS: Eighty subjects (mean age, 43.68 years) were randomized to receive study treatment. Forty subjects (20 men, 20 women) received emedastine plus placebo capsules, 20 (7 men, 13 women) received loratadine plus placebo eyedrops, and 20 (12 men, 8 women) received both active treatments. In the between-group efficacy comparison at visit 3, the difference in itching and hyperemia scores between emedastine and loratadine was statistically significant at all time points (all, P < 0.05). Efficacy scores for the combination of emedastine and loratadine were significantly better than those for loratadine alone at 2 of 3 time points for itching and all time points for hyperemia (P < 0.05). The combination was significantly better than emedastine alone at I of 3 time points for itching and 6 of 9 time points for hyperemia (P < 0.05). CONCLUSION: In this study, emedastine was more efficacious than loratadine for reducing the itching and redness associated with allergic conjunctivitis in the human conjunctival allergen challenge model.

Adult↗

Argon laser iridotomy in the treatment of patients with primary angle-closure or pupillary block glaucoma: a clinicopathologic study.

A "pulsed" argon laser was successful in 48 of 64 (75%) attempted laser iridotomies. Scanning and transmission electron microscopy performed on specimens taken at varying intervals following laser treatment revealed progressive scarring of iris tissue. The complications appear minimal at this time, but longer follow-up is required before it can be stated that laser and surgical peripheral iridectomies are comparable. However, the laser's simplicity and ease of administration appear to warrant its continued use at this time.

Argon↗

Q-switched neodymium:YAG laser iridotomy.

Twenty phakic eyes of 19 patients underwent Q-switched neodymium:YAG laser iridotomies for angle-closure glaucoma. Eleven eyes were previous argon laser failures. Penetration was achieved in each case with several shots in one session. Complications were minor and transient.

Eye Color↗

Foveal photocoagulation from laser iridotomy.

Acute and permanent loss of vision has resulted from foveal photocoagulation during argon laser iridotomy. This complication can occur when the laser beam passes through the iridotomy nearly parallel to the visual axis. This is most likely to happen during enlargement of the iridotomy. A retinal burn of the macular region through a peripheral iridotomy was produced experimentally, and the mechanism of this complication is explained.

Animals↗

Acute primary ischemic iris atrophy.

Five patients are described with acute primary ischemic iris atrophy with almost complete loss of the normal radial vessels of the iris and fine microneovascularization. The atrophy of the iris was marked with a thin atrophic stroma, widely dilated pupil, and extensive loss of pigment from the posterior surface of the iris. The condition is of unknown etiology but occlusion of the greater vascular circle of the iris is possible. Iris angiography showed an almost total loss of the radial vessels of the iris with some patchy microneovascularization. In recent cases, the onset was acute and all patients had a raised intraocular pressure (IOP) except one who had already undergone a drainage operation. There was an accompanying low-grade uveitis or cyclitis in the chronic stage in all cases. The condition was unilateral and the posterior segment of the eye was normal so that good visual function was possible if the accompanying cataract and glaucoma were appropriately managed.

Acute Disease↗

Risk analysis in the development of pterygia.

PURPOSE: No detailed analysis of risk factors in the development of pterygia has been previously performed. In this report, the authors identify and quantify these risk factors. METHODS: In a case-control study, 278 patients treated in a Brisbane hospital for primary pterygium between 1973 and 1978 were compared with a similar number of people without pterygium who were matched for age, race, and sex, using information from a standard questionnaire completed during a personal interview. RESULTS: Risk of pterygium was increased among patients who, in their third decade of life, worked outdoors in an environment with high surface reflectance of ultraviolet light compared with those who worked indoors. The elevation of risk was raised several hundred-fold among those subjects who worked mainly on sand compared with those who worked indoors when results were adjusted for associated risk factors. When risk was measured among subjects who worked in an environment that was mainly concrete, risk was increased almost 20-fold. Those subjects who spent their first 5 years of life at latitudes less than 30 degrees had almost 40 times the risk of pterygium than those living at latitudes greater than 40 degrees; spending the majority of times outdoors in these earliest years was associated with a 20-fold increase in risk of developing pterygium. There was a strong protective element in the wearing of regular glasses, sunglasses, or a hat. CONCLUSIONS: There is a strong suggestion of a causal relationship between ultraviolet light exposure and the development of pterygia during the early years of life and the cumulative exposure over the next 2 to 3 decades in occupations in which there is a high component of reflected ultraviolet light.

Adolescent↗

Breakdown of the blood-aqueous barrier after argon laser panretinal photocoagulation for proliferative diabetic retinopathy.

BACKGROUND: Breakdown of the blood-aqueous barrier (BAB) after panretinal photocoagulation (PRP) was measured with a laser flare photometer over a study period of 8 weeks. METHODS: Twenty-five eyes of 25 patients who had no previous photocoagulation and required such treatment for proliferative diabetic retinopathy (PDR) were included in the trial. They received 2000 burns (0.1-second exposure, 200 mu m spot) via a panfunduscope and 500 burns (0.1-second exposure, 500-mu m spot) with a Goldmann lens. Power levels were adjusted to produce a mild blanching of the retina. Only an argon green laser (514 nm) was used. Laser photometry was performed on both eyes at 3, 24, 48, 72, 96, and 168 hours and 8 weeks after laser treatment. RESULTS: Including all of the eyes treated, there was a significant increase in flare value of 3, 24, and 48 hours compared with baseline (Student's t test) but not at 72, 96, and 168 hours or at 8 weeks. Peak values occurred at 24 hours. When blue and brown irides were analyzed separately, there was a significant increase in flare for blue irides compared with baseline levels at 3 and 24 hours, whereas for brown irides the increased flare was sustained at 3, 24, 48, 72, and 96 hours (Student's paired t test). In addition, when the increase in flare value from baseline was compared between blue and brown irides (pooled Student's test), there was a sustained increase at 24, 48, 72, and 96 hours for brown irides compared with blue. Clinically significant uveitis, posterior synechiae, or peripheral anterior synechiae did not develop in any of the patients. CONCLUSIONS: Breakdown of the BAB may occur after PRP, particularly in more heavily pigmented irides. The time course of this suggests that the phenomenon is related directly to laser effects in the anterior segment, although other factors may contribute.

Anterior Eye Segment↗

Latanoprost. Two years' experience of its use in the United Kingdom. Latanoprost Study Group.

OBJECTIVE: The aim of the study was to assess the efficacy and safety of latanoprost in the long-term treatment of glaucoma. DESIGN: 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. PARTICIPANTS: In total, 277 patients were treated with latanoprost for up to 24 months. INTERVENTION: 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. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) was measured over the 24-month treatment period, and any ocular-systemic symptoms or adverse events were evaluated. RESULTS: 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. CONCLUSIONS: Latanoprost, administered once daily, is effective and well tolerated for the long-term treatment of patients with open-angle glaucoma or ocular hypertension.

Adrenergic beta-Antagonists↗

Corneal haze among blue eyes and brown eyes after photorefractive keratectomy.

BACKGROUND: To compare the incidence and severity of corneal haze after photorefractive keratectomy (PRK) among white patients with blue eyes and Saudi patients with brown eyes. DESIGN: Retrospective, nonrandomized, comparative trial. PARTICIPANTS: A total of 150 patients (71 females and 79 males) were included in this study. Two hundred sixty-six eyes of 150 patients were subjected to PRK. One hundred blue eyes of 50 white patients and 166 brown eyes of 100 Saudi patients were included in this study. METHODS: Two hundred sixty-six eyes of 150 patients were subjected to PRK with the Chiron Technolas Keracor 117C for the correction of myopia and astigmatism. MAIN OUTCOME MEASURES: All patients had complete ophthalmologic examinations, visual acuity testing, intraocular pressure, pachymetry, corneal haze assessment (0-4+), and computerized corneal topography. RESULTS: There were 266 eyes of 150 patients with 100 blue irides and 166 brown irides. The spherical equivalent was -0.50 diopter (D) to -8.75 D. The mean postoperative spherical equivalent at 6 months was -0.063 D (standard deviation [SD], +/-0.595) in blue eyes compared to -0.28 D (SD, +/-0.683) in brown eyes (P = 0.006). Ninety-five (95%) of 100 of the blue eyes achieved +/- 1 D of attempted correction compared to 148 (89.2%) of the 166 brown eyes. All patients with blue eyes had a visual acuity of 20/30 or better compared to 153 (92.2%) of the 166 brown eyes (P = 0.009). Forty-eight (18.04%) eyes had minimal to mild haze, 3 (1.12%) eyes had moderate haze, and 2 (0.75%) eyes had severe haze. The incidence of corneal haze among brown eyes was 48 (28.9%) of 166 eyes compared to 5 (5%) of 100 in blue eyes (P < 0.001). The difference remained significant after adjustment for age and gender with a P value of 0.0283. The relative risk for developing haze in brown eyes was found to be 7.72. CONCLUSION: The incidence of corneal haze after PRK was significantly higher among Saudi patients with brown irides than among white patients with blue irides. This suggests that racial factors may play a role in the development of corneal haze.

Adolescent↗

[Glaucoma in the melanoderm patient].

Much less marginal in France than believed, glaucoma in the melanoderm patient comes early in life, with a more aggressive progression leading to blindness twice as often as in the Caucasian patient. Generally open-angle glaucoma, it may be related to anatomical ocular characteristics of the Black population. Its management is not very different from that of glaucoma in the Caucasian patient.

Adult↗

Associations between prostate cancer susceptibility and parameters of exposure to ultraviolet radiation.

Low sunlight exposure confers increased prostate cancer risk. In a study conducted in northern England, we investigated how combinations of exposure measures affect this risk. Recursive partitioning was used to identify combinations of exposure parameters that distinguished 453 prostate cancers from 312 benign hypertrophy patients. Sunbathing score most significantly defined cancer patients; 78.7% men with low scores (</=3.0) and 40.2% men with high scores (>8.0) had cancer. These subgroups were stratified by childhood sunburning, holidays in a hot climate and skin type such that subgroups with a 13.0-fold increased risk of cancer were identified.

Adenocarcinoma↗