Alden Mead

Additive intraocular pressure lowering effect of various medications with latanoprost.

PURPOSE To determine the additive intraocular pressure reduction of various topical glaucoma agents used adjunctively with latanoprost. DESIGN Retrospective interventional case series. METHODS Retrospective evaluation of 73 eyes of 73 patients with glaucoma and inadequate intraocular pressure control on latanoprost alone. Each patient received adjunctive treatment with an additional glaucoma agent (dorzolamide, brimonidine, timolol, or other beta-blockers) for 1 year. RESULTS When added to latanoprost, dorzolamide lowered intraocular pressure an additional 3.9 mm Hg (19.7%, P <.001); beta-blockers further reduced intraocular pressure by 2.0 mm Hg (12.3%, P <.001), and brimonidine further reduced intraocular pressure by 2.0 mm Hg (9.3%, P =.0011). Dorzolamide dosed twice or three times daily was as effective as adjunctive therapy with latanoprost (P =.92). CONCLUSION Adjunctive therapy with dorzolamide provided a statistically significant intraocular pressure reduction at 1 year in eyes that were inadequately controlled with latanoprost alone.

A major pathway for the regulation of intraocular pressure

There has been a suspicion on the part of many clinicians and research scientists that intraocular pressure can be regulated by neural and/or humoral influences upon the rate of aqueous humor formation. It has been difficult, if not impossible, to separate specific influences of the central nervous system upon intraocular pressure from vascular induced or other secondary alterations. The past two decades have witnessed a great deal of study of the role of the adrenergic nervous system upon the regulation of intraocular pressure. From the investigations it is possible to formulate an integrated concept that can place years of work and speculation on a firm molecular foundation. The secretory tissue of the eye, the ciliary processes, contain an enzyme receptor complex, comprised by receptor complex, comprised by receptor bound membrane proteins, the catalytic moiety of the enzyme, a guanyl nucleotide regulatory protein (or N protein) and other features. The enzyme can be activated by well known neurohumoral or humoral agents that consist of catecholamines, glycoprotein hormones produced by the hypothalmic pituitary axis, and other related compounds, including placental gonadotropin. These compounds cause the ciliary epithelia to produce cyclic AMP at an accelerated rate. Cyclic AMP, as a second messenger, causes, either directly or indirectly, a decrease in the rate of aqueous humor formation that may be modulated by cofactors. Clinical syndromes fit the experimental data so that an integrated explanation can be given for the reduced intraocular pressure witnessed under certain central nervous system and adrenergic influences. The molecular biology of this concept provides important leads for future investigations that bear directly both upon the regulation of intraocular pressure and upon glaucoma.

Aqueous flow in human eyes is reduced by forskolin, a potent adenylate cyclase activator.

Forskolin, which lowers intraocular pressure in rabbits, monkeys, and human subjects, was tested for its effect on the rate of aqueous humor flow and on outflow facility. Topical sodium fluorescein was used to measure the rate of aqueous humor flow in forskolin or placebo treated eyes. Tonography was used to determine outflow facility before forskolin administration and at 3 hr after administration of the drug. In eight human subjects who showed reduction of intraocular pressure in response to a single drop of forskolin, flow was reduced by an average of 34%, compared to the contralateral eye during the same period of time. No significant change in outflow facility occurred. The action of forskolin in reducing intraocular pressure was the direct result of a reduction in net aqueous flow.

Ocular blood flow in phakic and aphakic monkey eyes

Alterations in regional ocular blood flow produced by topical epinephrine were studied in phakic and aphakic eyes of Macaca arctoides using the radioactive microsphere technique. Three isotopes were used to make sequential blood flow measurements just prior to topical epinephrine administration, 1 hr later and 3 hr later. Significant reductions of flow were found in the iris, ciliary body, and optic nerve head of both phakic and aphakic groups. Choroidal and posterior optic nerve flow decreased significantly in aphakic eyes only. Decreases in flow were flow decreased significantly in aphakic eyes only. Decreases in flow were maximal at 3 hr. Significant changes in retinal flow were not detected. The implications of these findings regarding epinephrine-induced aphakic cystoid macular edema and the suitability of epinephrine or its derivatives in the treatment of glaucoma are discussed.