Ophthalmic timolol in a hydrogel vehicle leads to minor inter-individual variation in timolol concentration in aqueous humor.

Ophthalmic timolol has been used for decades in the treatment of glaucoma and ocular hypertension, traditionally in aqueous 0.5% eye drops. Recently a timolol 0.1% hydrogel has been developed to improve systemic safety. The aim of the present study was to compare aqueous humor timolol concentrations after administration of 0.1% hydrogel and aqueous 0.5% timolol in patients scheduled for a cataract operation. The concentration in the aqueous humor was 210+/-175 ng/ml (mean+/-S.D.) 2h after administration of timolol 0.1% hydrogel and 538+/-304 ng/ml after aqueous 0.5% timolol. In the aqueous 0.5% timolol group more patients had unnecessarily high concentrations of timolol in the aqueous humor. beta(1)-receptors and beta(2)-receptors were practically 100% occupied after administration of both products. The hydrogel proved to be an excellent formulation in giving smaller inter-individual variation in penetration of timolol into the aqueous humor. Only a weak correlation was seen between corneal thickness and the aqueous humor concentration of timolol in the aqeuous 0.5% timolol group. In conclusion, in contrast to the conventional aqueous 0.5% timolol, 0.1% timolol hydrogel caused only slight inter-individual variation in timolol concentration in the aqueous humor.

Aqueous humour flow after a single oral dose of isosorbide-5-mononitrate in healthy volunteers.

PURPOSE: To investigate whether a nitric oxide donor given as a single oral dose is able to modify aqueous humour flow in healthy volunteers. METHODS: Ten healthy volunteers participated in a randomized, double-masked and placebo-controlled cross-over study. Aqueous humour flow was assessed by fluorophotometry after intake of isosorbide-5-mononitrate (ISMN), 10 mg. Topical timolol maleate, which is known to reduce aqueous humour flow, was used as a positive control. Intraocular pressure (IOP) was measured by applanation tonometry and blood pressure was registered. RESULTS: The basal rate of aqueous humour flow did not change significantly after a single oral dose of ISMN. The aqueous humour flow in the timolol-treated eye was reduced as compared to the contralateral control eye (p = 0.002). Mean IOP 6 hours after placebo and ISMN intake did not differ significantly. Timolol lowered IOP by 4 mmHg (p < 0.001). ISMN did not lower systolic blood pressure, but diastolic blood pressure was reduced by 4 mmHg (p = 0.048). CONCLUSION: A single oral dose of 10 mg ISMN had no significant effect on aqueous humour flow in healthy volunteers.

Corneally displaced malignant conjunctival melanomas.

PURPOSE: To characterize and classify malignant conjunctival melanomas with exclusively corneal invasive growth. DESIGN: Population-based, nationwide retrospective cross-sectional study. PARTICIPANTS: Patients with primary malignant conjunctival melanoma diagnosed between 1967 and 2000 in Finland. METHODS: On the basis of all available clinical and histopathologic data of tumors diagnosed during the study period, malignant conjunctival melanomas that first demonstrated invasive growth on the cornea without evidence of conjunctival tumors other than primary acquired melanosis were identified, their prevalence calculated, and their characteristics reviewed. On the basis of these cases and literature data, a classification for "corneal melanoma" was developed. MAIN OUTCOME MEASURES: Frequency and type of corneal involvement, recurrence, and survival. RESULTS: Patients with exclusively corneal invasive tumor accounted for 5% (95% confidence interval, 1-12) of 85 consecutive primary conjunctival melanomas. Two were separated from the limbus by clear cornea (type I), and two paralleled but did not invade the limbal conjunctiva (type II). Two were associated with clear evidence of primary acquired melanosis. None of the tumors recurred after local excision, and no metastases were observed during a median follow-up of 2 years 5 months (range, 1 year 8 months-7 years 10 months). CONCLUSIONS: Primary malignant conjunctival melanomas can grow on the cornea without conjunctival involvement other than acquired melanosis. They are easily removed and do not cause lymphatic metastases. The term "corneally displaced malignant conjunctival melanoma" would best describe their supposed conjunctival origin and actual corneal location.

Biochemical markers of the L-arginine-nitric oxide pathway in the aqueous humour in glaucoma patients.

PURPOSE: To study the role of the L-arginine-nitric oxide (NO) pathway in aqueous humour dynamics by measuring nitrate, nitrite and cyclic (cGMP) levels in guanosine 3',5'-monophosphate the aqueous humour of glaucomatous and nonglaucomatous cataract patients. METHODS: The study involved 38 glaucoma patients undergoing unilateral cataract surgery in the glaucomatous eye and 38 cataract control patients matched for sex, age, smoking habits and organic nitrate medication. All subjects underwent ophthalmic examination, and blood pressure was measured preoperatively. Nitrite, nitrate and cGMP levels were measured in aqueous humour and serum. RESULTS: The NOx (nitrite + nitrate), nitrite and cGMP concentrations in the aqueous humour were slightly higher in the glaucoma patients than in the control patients, but the differences did not reach statistical significance. The levels of cGMP in serum were higher in the glaucoma patients (P = 0.053). The subgroup of glaucoma patients with pseudoexfoliation had lower NOx and nitrite values in the aqueous humour (P = 0.046 and P = 0.345, respectively) than the matched controls, while cGMP levels were higher (P = 0.043). Levels of NOx and nitrite in the aqueous humour were higher in patients using oral nitroglycerin (P = 0.062 and P = 0.042, respectively) than in patients without this medication. Blood pressure was higher in the glaucoma patients, with a mean of 165/89 mmHg as compared to 153/81 mmHg in the controls (P-values 0.071/0.008). CONCLUSIONS: No differences in NO metabolites were found between glaucoma and control patients. However, any real changes may have been disguised by optimal medication of glaucoma. Low NOx and high cGMP levels in the aqueous humour of pseudoexfoliation patients warrant further evaluation in a larger study.

Implantable contact lens for high myopia.

PURPOSE: To evaluate the efficacy, safety, and biocompatibility of a collagen polymer implantable contact lens (ICL) (Staar Collamer) as a posterior chamber phakic intraocular lens (IOL) to correct high myopia. SETTING: Departments of Ophthalmology, Helsinki University Central Hospital, Helsinki, and Tampere University Hospital, Tampere, Finland. METHODS: A Staar Collamer posterior chamber phakic IOL was implanted in 38 eyes of 22 patients with a mean age of 39 years (range 24 to 54 years). The mean preoperative myopia was -15.10 diopters (D) (range -7.75 to -29.00 D). Surgical implantation was performed through a 3.0 mm clear corneal sutureless incision using paraocular anesthesia. The patients were followed clinically up to 3 years. The mean follow-up was 13.6 months (range 6 to 24 months) for refractive data and 22.3 months (range 6 to 35 months) for complications. The possible inflammatory response to the ICL was measured using a laser flare meter in 12 eyes. RESULTS: Postoperatively, all eyes had a significant increase in uncorrected visual acuity, allowing all but 3 patients (5 eyes) to manage most activities without spectacles. The mean spherical equivalent refraction at the last examination was -2.00 D +/- 2.48 (SD) (range +0.13 to -13.00 D), within +/-1.00 D of the targeted refraction in 31 eyes (81.6%) and within +/-0.50 D in 27 eyes (71.1%). In eyes in which the preoperative myopia was less than -18.00 D (n = 28), the achieved refraction was within +/-1.00 D of the intended refraction in 27 eyes (96.4%) and within +/-0.50 D in 24 eyes (85.7%). The refraction remained stable with a statistically insignificant change (P >.05) at each interval during the follow-up. The best corrected visual acuity (BCVA) improved by 1 or more lines in 23 of 32 eyes (71.9%) at 1 year. Two eyes (6.3%) lost 1 line of BCVA. Laser flare photometry showed normal aqueous flare values (11.71 +/- 6.61 photon counts/ms) in the 12 eyes measured at least 6 months after ICL implantation. Pupillary block glaucoma requiring surgical intervention occurred in 3 patients (7.9%). One patient (2.6%) developed cataract 1.5 years after ICL implantation; both ICLs were removed, and the refractive errors were corrected by lensectomy and implantation of low-power posterior chamber IOLs. One patient (2.6%) showed progression of dry macular degeneration at 17 months. CONCLUSION: At 1 year, ICL implantation had good visual and refractive results with excellent biocompatibility. Long-term follow-up is required to confirm that significant complications do not occur in most patients over time.