Melatonin Levels in Patients With Primary Open-angle Glaucoma With High or Low Intraocular Pressure.

PURPOSE: To evaluate circulatory melatonin levels by assessing nocturnal urinary excretion of 6-sulfatoxymelatonin (aMT6s) in patients with primary open-angle glaucoma (POAG) and to compare the high-tension group and the low-tension group. METHODS: This study included 80 eyes of 41 POAG patients and 87 eyes of 44 control subjects. POAG group was further classified into high-tension group and low-tension group according to the pretreatment intraocular pressure (IOP). The first urine in the morning was collected and aMT6s were measured using a commercial ELISA kit. Urinary aMT6s levels were expressed as ng aMT6s/mg creatinine. Differences in melatonin levels among the control and POAG subgroups were evaluated by generalized estimating equation adjusting age, sex, sleep duration, and intereye correlation. RESULTS: Urinary aMT6s/creatinine ratio did not differ between POAG and control group (P=0.097). The difference in the aMT6s/creatinine ratio between the 3 groups-high-tension group with baseline IOP≥21 mm Hg (19.74±3.12 ng/mg), low-tension glaucoma group with baseline IOP<21 mm Hg (26.71±3.47 ng/mg), and control group (30.35±3.05 ng/mg)-was statistically significant (P=0.046). Post hoc analysis revealed that the difference between the control and high-tension glaucoma groups was significant (P=0.014), whereas the difference between the control and low-tension glaucoma groups was not (P=0.436). CONCLUSIONS: This study found low melatonin levels in high-tension glaucoma compared with the control.

Ocular absorption, blood levels, and excretion of dorzolamide, a topically active carbonic anhydrase inhibitor.

Dorzolamide is a powerful inhibitor of carbonic anhydrase (CA) II that penetrates the sclera and cornea to reach the ciliary process and lowers formation of HCO3 and aqueous humor. The usual dose applied to the eye in treatment of glaucoma is 1 drop (30 microL of 2% solution) every 8 hr to each eye, or a total daily dose of 4 mg. On this regime, the red cells accumulated drug over a period of 8 days, reaching a value of 20-25 microM, which corresponds to the concentration of CA II in human red cells. This drug concentration persisted throughout the 18 months of application. The plasma concentration was 0.034 microM, or 1/700 that of the red cells. This plasma concentration corresponds to that calculated from the dilution of administered drug into body water. The data are well fitted into the equilibrium expression for KI of dorzolamide against CA II at 37 degrees C, as 8 x 10(-9) M. The red cells also contain a small amount (5 microM) of the N-des-ethyl metabolite, probably reflecting its modest binding to CA I. In the initial 8-day drug period, virtually none appeared in the urine since CA II sites were being filled. At steady state, renal excretion was 1.3 mg/day and the renal clearance 90 ml/min. These excretion numbers include the small (20%) amount of the des-ethyl metabolite of dorzolamide. The relation of these data to lowering of intraocular pressure is clear. By the systemic route, an inhibitor such as acetazolamide is effective when free drug concentration in plasma is 2.5 microM. In the case of topical drugs, as shown here, the plasma concentration is some 100 x lower, but the concentration in ciliary process is 2-10 microM, comparable to that following systemic drugs (1). In conclusion, the concentration in plasma (reflecting free drug) of dorzolamide is about 1/200 of that needed for systemic effects as seen following acetazolamide or methazolamide. Thus, there is a clear pharmacological basis for the lack of any physiological effects of ocular dorzolamide, except on the eye itself.