High-performance liquid chromatographic assay for antiinflammatory agents diclofenac and flurbiprofen in ocular fluids.

An HPLC assay for diclofenac (DC) and flurbiprofen (FP) in a 100-microliters sample of aqueous humour is presented. After acetonitrile extraction, the residue is analyzed using a reversed-phase octyl column and ultraviolet detection. The method is simple and reproducible. Excellent selectivity and resolution are achieved using an acetic acid-acetonitrile-triethylamine mobile phase. The lower limit of detection, defined as the amount of drug required to produce a peak twice the threshold, was ca. 0.3 ng DC on column and ca. 0.4 ng on column FP. The utility of the method is demonstrated by determining drug levels in aqueous humour of normal rabbits and of patients undergoing cataract surgery. The assay should be applicable to other antiinflammatory agents.

Intraocular diclofenac and flurbiprofen concentrations in human aqueous humor following topical application.

Flurbiprofen Na and diclofenac Na, two ocular antiinflammatory agents, were investigated to determine the aqueous humor concentrations in the human eye following topical application. One hundred sixty-five patients undergoing cataract surgery received a single drop of either diclofenac Na or flurbiprofen Na at selected times prior to the surgical procedure. Aqueous humor samples were aspirated at the beginning of surgery and a sensitive high-performance liquid chromatographic assay was used to determine the concentration of the antiinflammatory agent in the ocular fluid. Samples were obtained between 10 min and 24 hrs after a single instillation of the drug onto the cornea. The highest average concentration of diclofenac was 82 ng/ml at 2.4 hrs after instillation; concentrations remained above 20 ng/ml for over 4 hrs. Thereafter, between 3 and 16 ng/ml diclofenac could be assayed through 24 hrs. The highest average concentration of flurbiprofen, 60 ng/ml, was found at 2.0 hrs. The last detectable flurbiprofen concentration was measured at 7.25 hrs after instillation.

Pupillary capture of a posterior chamber lens following convulsive seizures.

Total pupillary capture of the optic of a posterior chamber intraocular lens (PC-IOL) occurred over 1 year after implantation, following severe, convulsive seizures. We suggest that the generalized seizures and associated extraocular muscle contractures created significantly elevated vitreous pressure, which caused anterior displacement of the IOL. To our knowledge, this is the first reported case of late pupillary capture of a PC-IOL following severe, convulsive seizures.

Effect of nasolacrimal occlusion on timolol concentrations in the aqueous humor of the human eye.

We studied the effect of manual nasolacrimal occlusion on the concentration of timolol in the aqueous humor of eyes of patients undergoing cataract extraction. Aqueous humor samples were obtained at various times after timolol maleate instillation from patients with or without 5 min of nasolacrimal occlusion; aliquots were assayed by HPLC. In patients receiving occlusion treatment, average timolol concentrations were statistically greater than those in control patients both between 15 and 90 min after instillation and also at 180 min. Pharmacokinetic analysis indicated that occlusion increased the concentration of timolol in the aqueous humor 1.7 times. In both groups, timolol concentrations were highest approximately 1 h after instillation. The decline in aqueous humor timolol concentrations occurred at similar rates in both groups.

Determination of trifluorothymidine in the eye using high-performance liquid chromatography.

A high-performance liquid chromatographic assay for trifluorothymidine in biological matrices of the eye is presented. Sample pretreatment was based on liquid-liquid extraction with ethyl acetate. Following evaporation, the residue was analyzed using a reversed-phase octadecylsilane column with ultraviolet detection. The lower limit of detection is ca. 50 ng/ml (ca. 3 ng on column). The method is simple, reproducible and selective. Concentrations of trifluorothymidine in the aqueous humour, vitreous humour and cornea of normal rabbits after a 50-microliters topical dose of 1% trifluorothymidine are reported.

The cornea and disorders of lipid metabolism.

Disorders of lipid metabolism, either hyperlipidemia or hypolipidemia, are associated with the formation of corneal opacities. Corneal arcus, the most commonly encountered peripheral corneal opacity, is frequently associated with abnormal serum lipid levels, but may occur without any predisposing factors. Reports also have linked corneal arcus with alcoholism, diabetes mellitus and atherosclerotic heart disease. Unilateral arcus is a rare entity that is associated with carotid artery disease or ocular hypotony. Diffuse corneal opacities associated with hypolipidemic disorders such as LCAT deficiency, fish eye disease and Tangier disease, may be the initial manifestation of these disorders and puts the ophthalmologist in a position to make an early diagnosis. Corneal arcus, along with a central corneal opacity, is seen in Schnyder's crystalline stromal distrophy. The association of the disorder with a dyslipidemia remains controversial. A review of lipid metabolism, corneal arcus and several disorders of lipid metabolism that affect the cornea are presented.

Aqueous humor pilocarpine and timolol levels after instillation of the single drug or in combination.

Aqueous humor levels of pilocarpine and timolol in rabbits after administration of either 2% pilocarpine or 0.5% timolol in single-drug solutions were compared with the concentrations found after instillation of a fixed combination of 0.5% timolol and 2% pilocarpine drops. Time intervals considered were 15 min, 30 min, 1 hr, 4 hr, and 8 hr after application. Drug concentrations were analyzed in individual aqueous samples by high-performance liquid chromatography. No statistically significant differences in either pilocarpine or timolol concentrations in aqueous humor were found at any time tested between the single-drug preparations and the combination.

Unilateral pseudo-synophthalmos.

A 4 1/2-year-old girl had an unusual congenital defect of her left eye which we have elected to call a unilateral pseudo-synophthalmos. We have found no other such case reported. We review the case history and findings, discuss the embryology, and explore the possible embryologic explanations for such an anomaly.

Influence of ophthalmic ointments on the penetration of pilocarpine drops.

To evaluate the influence of prior administered ointments upon the intraocular penetration of drops, we applied either a combination antibiotic ointment, a combination antibiotic-steroid ointment, or a lubricant ointment at different time periods before instillation of 2% pilocarpine drops into rabbit eyes. The level of pilocarpine measured in aqueous humor at one hour was compared to the level achieved in eyes without ointment application. No change was found in pilocarpine levels following application of the lubricant ointment. Pilocarpine concentrations were significantly lower (38%-48%) in animals receiving the antibiotic ointment at 5 or 15 minutes before pilocarpine drops. Pilocarpine levels also were decreased significantly when the steroid-antibiotic ointment was applied 15, 30 or 60 minutes before the drops. To verify these effects at other time periods, ointments were applied 15 minutes before pilocarpine drops and aqueous humor samples aspirated at 30 minutes or two hours. A 22% decrease in aqueous humor pilocarpine was found at 30 minutes with both the antibiotic and steroid-antibiotic combination; no effect was observed at two hours. To determine the influence of each drug component within the ointment on the penetration of pilocarpine, solutions of dexamethasone, neomycin, bacitracin and polymyxin B were mixed individually with pilocarpine drops and applied into the animal eyes. Bacitracin and polymyxin B significantly reduced one-hour pilocarpine levels in aqueous humor; however, no significant effect was observed with either neomycin or dexamethasone.

Prolonged aqueous humor levels of subconjunctival antibiotics after treatment with acetazolamide and/or timolol.

Many ophthalmologists routinely administer subconjunctival antibiotics at the end of cataract surgery for prophylaxis against bacterial endophthalmitis. Additionally they use acetazolamide and/or timolol to control intraocular pressure in the first 24-hour postoperative period. An animal study was undertaken to learn whether treatment with the aqueous humor suppressants, acetazolamide, and timolol prolongs the concentrations of antibiotics in the aqueous humor after subconjunctival administration of the antibiotic. Treatment with acetazolamide significantly increased concentrations of piperacillin; it had less consistent effects on tobramycin levels. Timolol treatment did not produce increased piperacillin concentrations at six hours; however, concentrations at 12 and 24 hours were significantly higher than in the controls. Timolol treatment increased tobramycin concentrations only at six hours. The combined use of timolol and acetazolamide produced significantly higher concentrations of piperacillin, but not of tobramycin.

Ophthalmic complications with disseminated intravascular coagulation.

Massive lid oedema, ecchymosis, proptosis with a total restriction of extraocular movement, markedly raised intraocular pressure, and occlusion of the central retinal artery developed acutely in the right eye of a 26-year-old woman with a past history of disseminated intravascular coagulation. She had been admitted to hospital for symptoms of abdominal pain and bleeding from multiple sites a few hours earlier. Five days previously she had some proptosis of the other eye and had been treated with antibiotics for suspected orbital cellulitis at another hospital. The oedema and proptosis resolved on high-dose intravenous corticosteroid therapy. Despite attempts to relieve the orbital oedema and raised intraocular pressure with a lateral canthotomy and antiglaucoma medications, the patient lost all perception of light in the right eye and has subsequently developed an optic nerve atrophy.

Comparative intraocular levels of pilocarpine achieved with drops and repository preparations.

The concentrations of pilocarpine in aqueous humor and iris-ciliary body of rabbits following topical treatment with repository preparations or conventional drop therapy were measured using high performance liquid chromatography (HPLC). Higher concentrations of pilocarpine occurred both in aqueous humor and iris-ciliary body following topical administration of the 4% gel product than with 4% drops. At 1 hour after administration, 2% drops produced a higher concentration of pilocarpine in the aqueous humor than occurred with the 1.86% pilocarpine emulsion product; however, isopilocarpine present in the emulsion product entered the aqueous humor in equal amounts with the pilocarpine. At 4 hours, equal concentrations of pilocarpine were present in aqueous humor and iris-ciliary body samples with both the 2% drop and 1.86% emulsion therapy. Pilocarpine concentrations were maintained within the aqueous humor of the eye for longer durations with both the gel and emulsion repository preparations than with comparable drop therapy.

Treatment of chalazia with corticosteroid injections.

Of 34 chalazia injected with triamcinolone acetate, 29 resolved after one or two injections. Larger lesions frequently required a second injection. During a six-month follow-up period, there were five recurrences; all occurred in lesions originally measuring larger than 36 sq mm. The response to intralesional corticosteroid injection was similar in all age groups and in lesions of short and long duration. Intralesional injection of triamcinolone acetate offers an acceptable alternative or adjunct to incision and curettage in the management of chalazia.

Pilocarpine concentrations in aqueous humor following single drop application. I. Effect of soft contact lenses.

Following single drop instillation of pilocarpine, drug levels in individual aqueous humor samples of rabbits were determined by high-performance liquid chromatography and correlated with changes in pupillary diameter and intraocular pressure (IOP). Application of higher concentrations of pilocarpine resulted in higher drug levels but these differences were neither statistically significant nor consistently proportional to the strength applied. Maximum miosis occurred between 30 and 60 minutes and the maximum fall in IOP occurred between 1 and 2 hours. The influence of contact lenses with varying water content and thickness upon intraocular penetration of pilocarpine was studied. Contact lenses did not affect 30-minute concentrations of pilocarpine in aqueous humor. Although two-hour levels were significantly lower with contact lenses, miosis and IOP at these time periods were comparable with and without lenses. Neither water content nor thickness appreciably influenced miosis and IOP.

High-performance liquid chromatographic assay for pilocarpine in aqueous humor.

A high-performance liquid chromatographic assay for pilocarpine has been developed for the determination of pilocarpine in aqueous humor. A structurally similar internal standard is used, and pilocarpine is separated from isopilocarpine under the chromatographic conditions used. A 100-microliter sample is mixed with an aliquot of internal standard at pH 8.3 and extracted with methylene chloride. The extract is evaporated to dryness and the alkaloids are quaternized with p-nitrobenzyl bromide. Following the quaternization, the sample is evaporated to dryness, washed and diluted with a mobile phase--triethylamine mixture and analyzed by high-performance liquid chromatography using a reversed-phase octadecylsilane column with detection at a wavelength of 254 nm. This is a highly sensitive, reproducible and selective assay for measuring pilocarpine at physiological levels in individual aqueous humor samples.

Outpatient sedation for ocular examination.

Outpatient sedation of infants, uncooperative children and, rarely, adults provides an opportunity to perform certain ophthalmologic diagnostic procedures such as tonometry, ophthalmoscopy and various electrophysiological studies (e.g., electroretinography and visual evoked response testing) without the expense and usage of an operating room. Many drugs have been recommended and used; all have limitations. The advantages and disadvantages of the more commonly used agents are reviewed. The known effects of these drugs on ocular function are presented.