Search

The ocular effects in rabbits of topically applied labetalol hydrochloride, a new alpha- and beta-adrenergic receptor blocking agent, were studied. A dose-related reduction in intraocular pressure (IOP) followed treatment with 0.01% to 1% solutions. Labetalol at a 1% concentration had no effect on pupil diameter. The same dose blocked an increase in IOP after water loading but did not significantly alter the coefficient of aqueous outflow facility. Mydriasis induced by phenylephrine hydrochloride was competitively inhibited.

With the use of an automatic titrator for calcium and a microcolorimetric assay for protein, diurnal variations in tear calcium and total protein values were studied in nine subjects during a ten-day period. Tear calcium and total protein concentrations were found to be individualized functions that were dependent on the sampling time and sampling day. Prolonged eye closure resulted in an approximate twofold increase in both tear calcium and total protein concentrations. The concentrations of both species remained relatively constant during the day between 8 AM and 5 PM, exhibiting few substantive variations. Diurnal changes in tear calcium and protein values closely paralleled one another. It was found that the tear concentrations of these two species could be related with a simple linear function, which suggests that calcium binding and transport by tear protein may be occurring.

We have obtained comparative data for the intraocular absorption of topically administered clindamycin hydrochloride hydrate and clindamycin phosphate, made feasible with a new gas chromatographic method of analysis. Results indicated that clindamycin phosphate underwent hydrolysis in the eye, liberating the biologically active clindamycin. However, topical clindamycin hydrochloride produced higher levels (two to six times more) of the antibiotic than those achievable with the phosphates ester in the uvea, aqueous humor, and cornea, presumably due to clindamycin hydrochloride's higher lipid solubility. Based on this data, clindamycin hydrochloride appears to be the preferred form of the antibiotic for topical ocular applications.

Following the suggestion that prostaglandins are involved in corneal neovascularization, two inhibitors of prostaglandin formation, prednisolone acetate and flurbiprofen sodium, have been evaluated in two experimental models of corneal neovascularization. The fatty acid cyclooxygenase inhibitor, flurbiprofen, at concentrations of 0.01% and 0.1%, significantly decreased the rate of vessel growth compared with vehicle controls in both silver nitrate cauterization and anterior chamber alloxan models of corneal neovascularization. Prednisolone, at a concentration of 1%, was used as a positive control. It did inhibit neovascularization in the latter model, but was ineffective in the former. It is concluded that 0.1% flurbiprofen is equipotent to 1% prednisolone as an inhibitor of corneal neovascularization. The mechanism is unknown but is likely to be via inhibition of prostaglandin formation and/or inhibition of leukocytic infiltration.

Prazosin hydrochloride, an oral antihypertensive, is reported to inhibit phosphodiesterase and block postsynaptic alpha-adrenergic receptors, intraocular pressure (IOP) in rabbits was reduced in a dose-related manner following topical ocular application of concentrations of 0.0001% to 0.1%. The ocular hypotensive response lasted six to eight hours with a maximum effect at approximately two hours. The IOP of unilaterally sympathectomized rabbits treated in both eyes with prazosin decreased more in the normal eyes than in the sympathectomized eyes. Treatment of only the unsympathectomized eyes of these rabbits elicited a similar response. Normal rabbits elicited a similar response. Normal rabbits treated in only one eye also showed a slight response in the contralateral eye. Preliminary experiments did not support the hypothesis that these effects were due to a decrease of systemic blood pressure. No substantial ocular toxicity or pupillary changes were observed.

Tear film breakup time (BUT) was measured in 25 normal subjects on 8 different occasions over a period of one month. Reproducibility of the BUT test and factors involved in interpretation of tear film breakup were studied. It was found that of 50 eyes, the average BUT ranged from five to 100 seconds, and that there were noticeable variations (P less than or equal to .05) in an individual eye from one patient visit to the next. The BUT is not a closely reproducible phenomenon in an individual eye.

Rosoxacin, a new synthetic antimicrobial agent, has a wide spectrum of activity that may prove beneficial in the treatment of ocular infections. To determine the penetration of rosoxacin into ocular tissues and serum of the rabbit after topical, subconjunctival, and intravenous (IV) administration, rosoxacin levels were measured using a microbiological assay after enzymatic digestion of the ocular tissues. Quantities of rosoxacin that should prove to be of therapeutic value were detectable in the anterior segment of the eye after topical or subconjunctival administration. Subconjunctival administration also resulted in high levels in the retina and choroid area and in the optic nerve. Low levels were detected in the retina and choroid 15 minutes following IV injection; however, no detectable levels were found in the ocular tissues after this period.

Tear calcium levels were measured in 27 normal subjects. An instrumental technique that required only 5- to 10-microL tear samples was used for this purpose. A mean of 2.11 +/- 49 (SD) mg/dl of calcium with a range of 1.05 to 3.49 mg/dl was determined for 67 tear samples from 27 subjects. This is in excellent agreement with more elaborate and previous methods. Various factors involved in tear calcium levels were also studied. Tear calcium levels were not significantly affected by the normal walking-hour wear of either hard or soft contact lenses among 22 women aged 19 to 35 years. Tear calcium day-to-day and diurnal variations were found for five of five subjects in a three-day study. Further studies of these variable phenomena are indicated.

Two double-blind, random-assignment clinical trials demonstrated the effectiveness of topical oxymetazoline hydrochloride in reducing histamine-induced hyperemia. Oxymetazoline hydrochloride at an optimum strength of 0.025% produced a marked and prolonged reduction of hyperemia, with the onset of effect occurring within one to five minutes of instillation. Safety indicators, including BP, heart rate, intraocular pressure, pupil size, and visual acuity, did not change significantly from baseline values. Oxymetazoline was absorbed slowly into the eye: only 0.006% of the original drug concentration was found in the aqueous humors of rabbits 30 minutes after instillation; the balance remained primarily in external ocular tissues. Metabolic studies in rabbits indicated that excreted amounts of unmetabolized radioactive oxymetazoline in urine following drug administration were similar (23%) for the ocular and nasal routes of application. The proportions of oxymetazoline metabolite to unchanged oxymetazoline were constant for all administration routes tested.

To our knowledge, this is the first report of a topically applied, specific adenylate cyclase activator that reduces intraocular pressure. Forskolin, a novel adenylate cyclase activator, is reported to increase cyclic adenosine monophosphate (AMP) in intact cells. Cyclic AMP levels are increased with various antiglaucoma agents. Intraocular pressure in rabbits was significantly reduced with two concentrations of forskolin, 0.1% and 0.05%. Ocular hypertension was noted with 0.05% and 0.2%. No change in IOP was noted with 0.01% forskolin. The IOP lowering with 0.1% and 0.05% forskolin lasted approximately six hours. Mild, transient conjunctival chemosis was noted in the doses that decreased IOP. The contralateral control eye showed decreases in IOP, but the differences between control and tested eyes were significant by the Student's paired t test.

A new automatic objective refractor was used on healthy adults. In the absence of cycloplegic drugs, spherocylindrical objective refractions performed with the instrument provided 20/20 acuity 96% as often as with standard subjective techniques. No instrument-induced accommodations effects were seen. One hundred percent of instrument spherical findings were repeatable within 0.50 diopters; all cylindrical findings were repeatable within 0.37 D. This result represents a higher level of repeatability than that reported for standard subjective refraction under clinical conditions. In the absence of cycloplegic drugs, the correlation coefficient between the instrument's findings and standard subjective spherical findings was .97 v .98 between two practitioners' subjective refractions. The average difference between cylindrical findings of the instrument and those of an experienced practitioner was 0.04 D larger than the average difference seen between two practitioners using subjective techniques.

Ocular penetration of lincomycin hydrochloride in albino rabbits was determined by bioassay. On topical application, the frequency of multiple instillation of drops played an important role in producing therapeutic levels in the anterior chambers. Therapeutic levels were attained in the cornea, aqueous humor, and iris-ciliary body, with peak values occurring at 30 to 45 minutes. Varying the pH of the dosing solution did not change ocular absorption and distribution substantially. Removal of corneal epithelium, however, greatly enhanced absorption. Relative to clindamycin, lincomycin hydrochloride had longer onset of peak values and lower overall concentration in ocular tissues. Intravitreous injection of lincomycin hydrochloride produced therapeutic and steady levels of antibiotic in anterior chambers. Injection produced a concentration in aqueous humor twice that achievable topically. The major route of elimination from the posterior chamber was through retina-choroid.