dapiprazole and Hyperemia

Dapiprazole HCL is currently available in the United States for reversal of diagnostic mydriasis. The recommended dosage for this indication is 2 drops followed 5 minutes later by 2 drops. We studied the dose-response profile and tolerance of three different treatment regimens: 1 drop alone, 1 drop followed by 1 additional drop 5 minutes later, and 2 drops followed by 2 additional drops 5 minutes later. Sixty normal male and female volunteers between 18 and 40 years of age were recruited for a double-masked, placebo-controlled, crossover study in which each eye of each subject was dilated with 2.5% phenylephrine. After one hour, one eye was treated with 0.5% dapiprazole, and the contralateral eye was treated with placebo. Each subject was treated with each of the three dapiprazole regimens in three different study sessions separated by at least 5 days (drug half-life in the eye is 5 hours). Analysis of AUC demonstrated no significant difference (P = 0.620) between the 1 drop regimen and the 2 + 2 regimen. A single drop of dapiprazole has a clinical effect equivalent to the 2 + 2 drop regimen in eyes dilated with 2.5% phenylephrine, which should improve the cost-effectiveness of this mydriolytic agent.

Topics: Accommodation, Ocular; Adolescent; Adrenergic alpha-Antagonists; Adult; Area Under Curve; Conjunctival Diseases; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Hyperemia; Male; Mydriatics; Ophthalmic Solutions; Phenylephrine; Piperazines; Pupil; Triazoles

We evaluated the clinical usefulness of dapiprazole in reversing the effects of tropicamide 1.0%. Our study was random, masked with placebo, and used one eye of each subject as a control. Thirty subjects were given dapiprazole as directed by the manufacturer 30 min after being dilated by one drop each of proparacaine 0.5%, tropicamide 1.0%, and then 5 min later another drop of tropicamide 1.0%. Pupil diameter, amplitude of accommodation, conjunctival injection, and intraocular pressure were evaluated. Each of these variables was measured: (1) before instillation of the diagnostic agents; (2) before the instillation of dapiprazole; and (3) at 30, 60, 120, and 180 min after the final instillation of dapiprazole. The average pupillary recovery time for dapiprazole-treated eyes was significantly less than for nontreated eyes. Accommodation also showed faster recovery. Comfortable reading ability returned after approximately 43 min with dapiprazole vs. 66 min without dapiprazole. All of our subjects exhibited conjunctival hyperemia after the administration of dapiprazole. This persisted throughout the 180 min observation period after its administration.

Topics: Accommodation, Ocular; Adrenergic alpha-Antagonists; Adult; Conjunctiva; Double-Blind Method; Humans; Hyperemia; Intraocular Pressure; Ophthalmic Solutions; Piperazines; Pupil; Triazoles; Tropicamide

A study was performed to evaluate the clinical usefulness of dapiprazole in a private clinical setting. This study was unmasked, but used one eye of each subject as a control. Thirty consecutive subjects were given dapiprazole as directed by the manufacturer. The administration of dapiprazole followed bilateral dilation for routine fundus examination. Subjects were dilated using one drop each of proparacaine 0.5%, tropicamide 1.0%, and phenylephrine 2.5%. Pupil diameter, amplitude of accommodation, and conjunctival injection were evaluated. Each of these three variables was measured (1) before instillation of the diagnostic agents, (2) before the instillation of diapiprazole, and (3) at 30, 60, 120, and 180 min after the final instillation of dapiprazole. The average pupillary recovery time for dapiprazole-treated eyes was similar to previously published data. Accommodation also showed significant recovery, with comfortable reading ability returning after approximately 30 min. The design of our study did not permit us to determine what portion of accommodation recovery was attributable to alpha ciliary muscle effect and what portion resulted from the increased depth of field that was due to the pupillary constriction. All of our subjects exhibited conjunctival hyperemia after the administration of dapiprazole. This side effect persisted through the entire 180-min observation period that followed dapiprazole administration.

Topics: Accommodation, Ocular; Adrenergic alpha-Antagonists; Adult; Ciliary Body; Conjunctiva; Humans; Hyperemia; Ophthalmic Solutions; Phenylephrine; Piperazines; Pupil; Triazoles; Tropicamide

Evaluation of ocular hyperemia has been an important assessment in research studies of effects of contact lenses, medications, and pollutants on the eye. Hyperemia has been difficult to quantitate objectively. The purpose of this study was to validate a computer based image analysis system to quantitate hyperemia automatically and objectively in pixelated images of the external eye using two measures, the percent of the red color, RR, and the fraction of pixels which are blood vessels, VA. Validation was against an established photographic reference scale of ocular hyperemia and against the clinical pharmacologic effects of 0.5% dapiprazole hydrochloride, known to increase hyperemia, and 2.5% phenylephrine hydrochloride, known to decrease hyperemia. Color transparencies from the reference scale were converted to digital images. Temporal and nasal regions of the external eye were imaged directly to magnetic disk before and after pharmacologic intervention. Custom software automatically excluded unwanted regions, and quantitative image analysis produced RR and VA. RR and VA were each correlated with the reference scale. For each region and for each pharmacologic intervention, the mean RR and the mean VA, respectively, were compared at time zero and at a mean elapsed time of 713 +/- 47 s. RR and VA consistently increased as the hyperemia in the reference scale increased. Pearson correlation coefficients were 0.98 and 0.99, respectively, (p < 0.01). At 713 +/- 47 s after each pharmacologic intervention, RR and VA increased and decreased as expected (p < 0.001). Thus, this study successfully validated the methodology against expert clinical judgment and was able to measure automatically and objectively clinical changes in ocular hyperemia.

Topics: Adult; Algorithms; Evaluation Studies as Topic; Eye; Female; Humans; Hyperemia; Image Processing, Computer-Assisted; Male; Phenylephrine; Piperazines; Reference Values; Triazoles