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.

Disappearance of Kayser-Fleischer rings after liver transplantation.

Kayser-Fleischer rings were observed in a 14-year-old boy with progressive liver disease. Laboratory data supported a diagnosis of hepatolenticular degeneration (Wilson's disease). Therapy with chelating agents was initiated, but discontinued because of side reactions. Successful liver homotransplantation was performed. The Kayser-Fleischer rings gradually faded and had completely disappeared by six years postoperatively.

Conjunctival flora in patients receiving immunosuppressive drugs.

The bacterial, fungal, and viral flora of the conjunctiva were compared in patients receiving immunosuppressive drugs and in a control group of patients seen for routine eye examinations. The lysozyme concentration of the patients' tears was also measured. No significant difference was found in the number of positive cultures nor in tear lysozyme content in the two groups. A positive correlation was noted between increasing doses of prednisone and the number of bacterial organisms found in the patients' conjunctiva.

Effectiveness of generic acetazolamide.

Comparisons were made between the ocular hypotensive effects and blood levels achieved with the single-dose administration of either generic acetazolamide or brand-name acetazolamide (Diamox). The relative cost of the two products was surveyed. The effect of food on the absorption of acetazolamide was also evaluated. The generic and brand-name acetazolamide were equivalent in their effects on intraocular pressure. Comparable blood levels of acetazolamide were obtained with the two products. The cost of generic acetazolamide was 37% less than brand-name acetazolamide, when available. Food intake did not appear to influence the absorption of acetazolamide.

Ophthalmic ointments.

The use of ointments as an ocular drug vehicle adds an important dimension to topical therapy. Ointments are well tolerated, fairly safe, and provide an excellent means for enhanced ocular contact time. In the case of certain antibiotics, this improved contact time yields increased ocular drug levels. However, experimental data indicate that corticosteroid ointments do not penetrate into the eye as well as do suspension preparations. This may relate to the binding of the drug to the ointment base and also to the particular steroid compound. Like other ophthalmic preparations, ointments may become contaminated. Ophthalmic ointments should not be instilled into eyes with open wounds. Instillation of ointments into postoperative eyes where wound closure is secure appears to be safe and effective.

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.

Aspergillosis of the orbit with immunosuppressive therapy.

A case report of aspergillosis of the orbit in a 27-year-old renal transplant patient receiving immunosuppressive therapy is presented. The predominant clinical features were slowly progressive, painful exophthalmos and fever of undetermined origin. Orbital biopsy established the diagnosis. The histopathologic characteristics of the infectious process changed from the time of biopsy to the time of autopsy, reflecting the patient's changing immunologic status.

The effect of general anesthetic agents on intraocular pressure.

General anesthetics may have diverse effects on intraocular pressure, possibly leading to serious complications such as vitreous loss and iris prolapse. Clinical and research findings on the effects of depolarizing and nondepolarizing agents are discussed, and methods of avoiding or counteracting adverse reactions are summarized.

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.

Occlusion of the central retinal artery after retrobulbar corticosteroid injection.

Occlusion of the central retinal artery with loss of all vision occurred in a 38-year-old white woman given a retrobulbar injection of betamethasone acetate and betamethasone disodium phosphate (Celestone Soluspan) for the treatment of a retrobulbar neuritis. Ophthalmoscopy revealed embolic, whitish material within several of the small retinal arterioles and capillaries. This, together with the absence of any signs of retrobulbar hemorrhage, suggested that the corticosteroid material was accidentally injected into a branch of the central retinal artery and subsequently passed into the main vessel.

Effect of local anesthetics on intraocular penetration of subconjunctival antibiotics.

The combination of the subconjunctival injection of lidocaine HCl or procaine HCl with the subconjunctival injection of penicillin G, methicillin, cephaloridine, or gentamicin did not influence their intraocular penetration or subsequent antibiotic activity in aqueous humor of experimental animals.

Nontraumatic rupture of the globe secondary to orbital cellulitis.

A 53-year-old woman had a spontaneous nontraumatic rupture of the globe secondary to severely increased orbital pressure from an orbital cellulitis. To our knowledge this is the first such case reported.

Glycerol and hyperosmolar nonketotic coma.

Hyperosmolar nonketotic coma occurred in a 29-year-old diabetic man with chronic renal failure after the repeated use of oral glycerol for treatment of acute neovascular glaucoma. Treatment with intravenous hypotonic saline, albumin, and packed red blood cells together with insulin and bicarbonate was successful in overcoming the coma.

Plasma complement and histamine changes after intravenous administration of sodium fluorescein.

Venous blood samples were obtained from 85 patients before and at three, ten, and 30 minutes after intravenous administration of sodium fluorescein. Whole complement hemolytic activity and plasma histamine were measured. The patients were observed for side effects. Clinical adverse reactions occurred in 18 (21%) of the patients. Changes in complement hemolytic activity occurred in all patients, but probably were the result of binding of fluorescein to complement proteins, or on the membrane of sensitized red blood cells used in the assay. Plasma histamine was increased within the first few minutes after infusion of fluorescein and persisted up to ten minutes. Increased histamine was found in 66% of patients with adverse reactions and in only 15% of patients with no reactions. Histamine may be an important mediator of adverse reactions to fluorescein.

Corneal distribution of subconjunctival antibiotics.

Radioactive carbon-labeled penicillin G, chloramphenicol, or gentamicin were injected subconjunctivally into rabbit eyes. The distribution of antibiotics throughout the cornea was determined in relation to the injection site; aqueous humor levels were also measured. For chloramphenicol, the highest drug concentrations in the cornea were adjacent to the injection site; levels decreased as the distance from the injection site increased. For penicillin G and gentamicin, highest corneal levels were adjacent to the injection site. Levels were lowest in the central cornea but increased in the peripheral cornea, 180 degrees opposite the injection site. For all antibiotics, therapeutic levels were reached throughout the cornea irrespective of the injection site. Corneal values for all drugs were consistently higher than aqueous humor values. These results suggest that in the treatment of corneal ulcers the choice of subconjunctival injection site is not important.

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.

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 acetazolamide in biological fluids by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) assay for acetazolamide is presented. A 100-microliter sample is mixed with an aliquot of the internal standard solution and the mixture, buffered at pH 4.5, is extracted with ethyl acetate. The extract is evaporated to dryness and the residue is analyzed by HPLC, using a reverse-phase octadecylsilane column. The wavelength of the detection is 254 nm. The coefficient of variation (CV) in the within-day analysis of replicate 10-microgram/ml acetazolamide samples in human blood plasma was 6.5%, while the between-day CV was 7.1%. The procedures was developed for the 1-25 microgram/ml acetazolamide concentration range. The internal standard used is similar in chemical structure to acetazolamide and can be readily prepared in one step from a commercially available precursor. In addition to blood serum or plasma, the assay can also use aqueous and vitreous humor samples. Theophylline and acetaminophen interfere in the assay. The technique was used to determine the concentration of acetazolamide in the blood serum of human volunteers after an oral dose of the drug, and in the aqueous and vitreous humors of rabbits after an intravenous dose of acetazolamide.

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.

Inactivation of aminoglycoside-penicillin combinations after subconjunctival injection.

A study was undertaken to determine the extent of inactivation of gentamicin, tobramycin, ticarcillin and carbenicillin when given subconjunctivally in amino-glycoside-penicillin combinations. Rabbits were injected with such a combination in either the same or opposite subconjunctival sites. The aqueous humor was aspirated and bioassayed for antibiotic activity at 1 and 4 hours after injection. The influence of the aqueous humour upon antibiotic inactivation was studied by in vitro experiments. Ticarcillin penetrated into the aqueous humour better than carbenicillin. Some chemical inactivation of all the antibiotics given in combination occurred. There was less inactivation of the aminoglycosides at 4 hours when the antibiotics had been injected at opposite poles. The inactivation occurred primarily within the aqueous humour but to a lesser extent in the subconjunctival space. The degree of inactivation is likely of little clinical significance with the doses usually used.