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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.

Administration, Topical↗

Short-term oxidative status of lens and aqueous humor after excimer laser photorefractive keratectomy.

PURPOSE: Oxidation in the anterior ocular segment is associated with cataractogenesis and possible complications to corneal endothelium. We investigated whether oxidation occurred in the rabbit anterior ocular segment shortly after excimer laser photorefractive keratectomy (PRK). METHODS: Rabbits were treated unilaterally with PRK, the other eye serving as a control. Aqueous humor sampled shortly after treatment was assayed spectrophotometrically for hydrogen peroxide using ferrous oxidation in xylenol in the presence (group 1; n=10), or absence of oxygen (group 2; n=8). Oxidized glutathione and malondialdehyde levels were measured in lenses by spectrophotometry and HPLC. RESULTS: Hydrogen peroxide concentration of aqueous humor was not different between treated (77 +/- 36 microM) and control eyes (88 +/- 34 microM) in the oxygen group or the nonoxygenated group (treated eyes: 6.7 +/- 5.4 microM and control eyes: 5.5 +/- 4.7 microM). Peroxide levels did not correspond to endogenous H2O2 but presumably reflected action on ascorbic acid. There was no difference in the percent of oxidized glutathione between experimental and control eyes. Malondialdehyde could not be detected in the lens of treated or control eyes, despite good sensitivity in recovery assays. CONCLUSION: Based on these assays, there is no evidence that PRK oxidizes the aqueous humor or the lens of treated rabbits within 10 minutes of treatment.

Animals↗

Isolation of a vesicular virus belonging to the family rhabdoviridae from the aqueous humor of a patient with bilateral corneal endotheliitis.

PURPOSE: To report bilateral corneal endotheliitis caused by a vesicular virus (family Rhabdoviridae). METHODS: Case report of a 49-year-old man with a complaint of sudden onset of decreased vision in both eyes had diffuse corneal stromal edema with extensive folds in Descemet's membrane and was diagnosed as having bilateral viral endotheliitis. Virologic investigations were performed using aqueous humor from the right eye. RESULTS: An ether- and chloroform-sensitive cytopathic agent was isolated in Vero and BHK-21 cell lines from the aqueous humor. It was identified as a vesicular virus belonging to the family Rhabdoviridae by electron microscopy. Neutralizing antibody was demonstrated at a titer greater than 1 in 4,096 dilutions in the convalescent serum. Neurologic complications included loss of hearing and postinfectious polyradiculopathy affecting both lower limbs. Best-corrected visual acuity was 20/120 OD and 20/20 OS. Six months later, he developed glaucoma in the right eye. Trabeculectomy with intraoperative application of 5-fluorouracil was performed. CONCLUSION: This is the first report of bilateral endotheliitis caused by a vesicular virus and confirmed by virus isolation from the aqueous humor of the affected eye.

Aqueous Humor↗

Ciliary ganglion stimulation. II. Neurogenic, intraocular pathway for excitatory effects on aqueous humor production and outflow.

Data obtained suggest that preganglionic stimulation of the ciliary ganglion produces an increase of aqueous humor formation and of facility of outflow "C" through the following neurogenic pathway: (1) the preganglionic fibers synapse in the ciliary ganglion as evidenced by depression of the response with nicotine applied topically to the ganglion. (2) The impulse proceeds to the equivalent of an intraocular interneuron which can be blocked by low concentrations of atropine and has been previously identified as being an E-2 receptor site. (3) From the interneuron, activity is ultimately exerted without further synapse on alpha-adrenergic receptors through the release of norepinephrine from the neuronal terminals. The adrenergic mechanism of action is supported by the inhibition of the responses by phenoxybenzamine, bretylium, and guanethidine. Constriction of efferent ciliary process blood vessels by neuron-released norepinephrine seems to be the end effect responsible for the increased production of aqueous humor. The site of the end response to increase "C" is unclear.

Acetylcholine↗

Anterior chamber to frontal sinus shunt for the diversion of aqueous humor: a pilot study in four normal dogs.

Silicone tubing was used to divert aqueous humor from the anterior chamber of the right eye to the rostral compartment of the right frontal sinus in four clinically normal mixed-breed dogs. Biomicroscopic examination, and pneumoapplanation tonometry and tonography, completed for up to 18 weeks postoperatively, confirmed gonioimplant function in all four cases. The dogs were euthanized at 6, 8, 16 and 18 weeks postoperatively. Gonioimplant patency was further confirmed by postmortem examination of the globes, implants and frontal sinuses. Gross and light microscopic examinations revealed iridal attachments to the implant (n = 4), mild anterior uveitis (n = 3), anterior subcapsular cataracts (n = 4), and focal corneal (n = 3) and scleral (n = 3) scarring in the operated globes. Light microscopic examination of frontal sinus specimens revealed mild lymphocytic proliferation and fibrosis immediately adjacent to the implant entrance site. There were no bacteria detected on aerobic or anaerobic cultures of the frontal sinuses or light microscopic examination of the globes or frontal sinuses. Results indicate that the frontal sinus shunting of aqueous humor is a safe and effective means of extraorbital aqueous diversion with potential applicability in the management of glaucoma.

Journal Article↗

[Determination and significance of catecholamines in aqueous humor, plasma and 24 hour urine of patients with acute angle-closure glaucoma].

OBJECTIVE: To study the functional state of ocular and systemic sympathetic nervous system and the effects of its related neurohumoral factor, catecholamines (CA), on intraocular pressure (IOP) in patients with acute angle-closure glaucoma (AACG). METHODS: The levels of CA in the aqueous humor, plasma and the total amount of CA in 24 hour urine of cases with AACG during attack stage were determined with fluorometry, and the results were compared to that of patients with senile cataract and normal adults. RESULTS: The CA levels within aqueous humor and plasma and in 24 hour urine of the patients with AACG during attack stage were elevated obviously as compared with that of the control subjects (P < 0.001), and positively correlated with the level of IOP. CONCLUSION: During attack stage of AACG, the ocular sympathetic nervous system is highly excited and a large amount of CA is released into the aqueous humor, in the meantime the systemic sympathetic nervous system is also excited and CA is released into the blood circulation, which may play a certain role in the regulation of IOP. Possibly, CA is an important supplemental factor within the attack stage of AACG.

Acute Disease↗

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.

Animals↗

Interleukin 4, IgG and oligoclonal IgG in aqueous humor of cataract patients.

We measured interleukin 4, total IgG, IgG-albumin relative concentration ratio, and oligoclonal IgG in aqueous humors of patients with uncomplicated senile cataracts and cataracts complicated by previous uveitis of unknown etiology. The values of all mentioned parameters are significantly elevated in aqueous humors of patients with complicated cataracts. The possible implications of our findings are briefly discussed.

Aged↗

Influence of rectus eye muscles tenotomy on the aqueous humor composition in rabbits.

INTRODUCTION: Anterior segment ischaemia manifesting in aqueous malformation may follow tenotomy of the extraocular muscles. MATERIAL AND METHODS: Tenotomy of 2 or 4 rectus eye muscles was performed on the right eyes of 23 adult rabbits. The aqueous humor was withdrawn from the anterior chamber of both eyes in 7 rabbits on the 11th, on the 22nd in 8 and on the 32nd postoperative day in 8 rabbits. Aqueous natrium, potassium and glucose concentrations and protein electrophoresis were examined. RESULTS: The only significant change was lower mean aqueous potassium concentration in the operated eyes as compared to controls on the 11th postoperative day. CONCLUSION: Tenotomy of rectus eye muscles in healthy rabbits evoked a discrete blood-aqueous barrier break-down.

Albumins↗

[Correlation between tyndallometry with the "laser flare cell meter" in vivo and biochemical protein determination in human aqueous humor].

INTRODUCTION: The laser flare-cell meter allows noninvasive measurement of aqueous flare in humans. In vitro studies have shown good correlations between flare values and albumin concentrations. In this study, we compared aqueous flare values and aqueous protein concentrations in living human eyes. PATIENTS AND METHODS: We measured aqueous flare and the total aqueous protein concentration in 52 eyes of 52 patients (age 58.4 +/- 18.8 years) that underwent cataract extraction (22 eyes) or trabeculectomy (30 eyes). Before surgery, aqueous flare was determined with the laser flare-cell meter (Kowa FC-1000). During surgery, 50 microliters of primary aqueous humor was aspired, and total aqueous protein concentration was performed using a modified Pierce-BCA assay. Linear regression analysis was calculated. RESULTS: There was a high correlation between aqueous flare values and total aqueous protein concentration (y = 0.52x + 0.15, r = 0.98, p < 0.00001). This correlation was observed both in eyes with and without cataract. CONCLUSION: Our results indicate that aqueous flare values as determined with the laser flare-cell meter reflect the true aqueous protein concentration quite accurately. Lens opacities appear not to significantly alter the results of aqueous flare measurements. As expected by theoretical assumptions, flare measurements overestimate aqueous protein concentrations in eyes with severely impaired blood-aqueous barriers because, according to Rayleigh's law, larger protein molecules cause more light scattering. However, transformation and expression of flare values as "albumin concentration equivalents" according to in vitro-calibration may still be useful, especially if the results of different instruments are to be compared.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Leukotrienes levels in the aqueous humor following experimental ocular trauma.

Using radioimmunoassay technique, levels of leukotriene B4 and C4 (LTB4 and LTC4) in the aqueous humor of rabbit eyes were measured following experimental nonpenetrating ocular trauma. Slit lamp examination showed a time-dependent increase of flare, cells, and fibrin in the anterior chamber of the traumatized eyes. Polymorphonuclear (PMN) leukocyte influx into the aqueous humor was not seen at 6 hours but increased significantly in traumatized eyes after 12 hours. No inflammatory cells were observed in control eyes. Histopathologic studies demonstrated injuries of the ciliary body, ruptures of the retina and choroid, with intraocular hemorrhage. LTB4 values peaked at 6 hours, prior to PMN cell infiltration and remained significantly higher than controls, which remained undetectable at all intervals after injury. LTC4 values also peaked by 6 hours in the traumatized eyes. These data demonstrate that elevations in LTB4 and LTC4 are associated with blunt trauma, and this precedes PMN cell infiltration. Leukotrienes may play a role in the early inflammatory response following concussive ocular injuries.

Animals↗

Analysis of immediate changes of water-soluble metabolites in alkali-burned rabbit cornea, aqueous humor and lens by high-resolution 1H-NMR spectroscopy.

PURPOSE: To investigate immediate changes in water-soluble metabolites of ocular tissue in alkali-burned eyes by using high-resolution 1H-NMR spectroscopy. METHODS: Adult New Zealand rabbit eyes were burned with 1 M NaOH for 1 min. Normal eyes were used as control. Samples from aqueous humor and perchloric acid extracts of the cornea and lens were analyzed on a NMR spectrometer operating at 500 MHz for protons. Metabolites were quantified by comparing peak area with an added internal standard, TSP (3'-trimethylsilylpropinate-2,2,3,3-d4). RESULTS: Alkali burn of corneal surface causes immediate changes in concentration of many water-soluble metabolites in the anterior segment. Even as far away as the lens a significant increase in lactate was found. Cornea showed a significant increase in glucose and a significant decrease in hypo-taurine concentration. Most changes were observed in aqueous humor, with significant increases in succinate, creatine, scyllo- and myo-inositol and a significant decrease in citrate concentration. Furthermore, a small decrease in ascorbate concentration in aqueous humor was observed. CONCLUSIONS: The present study provides a valuable contribution to the knowledge of metabolic alterations in alkali-burned eyes. It shows that 1H-NMR spectroscopy is well suited for simultaneous qualitative and quantitative analysis of changes of metabolite concentrations in damaged tissues. This can help us to better evaluate and understand the biological alterations due to alkali burn.

Amino Acids↗

Aqueous humor flow in unilateral carotid stenosis.

Our purpose was to study the relationship between carotid artery occlusive disease and aqueous flow in human subjects. Aqueous humor flow was measured by fluorophotometry in seven patients with unilateral carotid artery disease documented by oculoplethysmography. The mean (+/- SD) flow was 2.03 +/- 0.38 microliter/min in the affected eyes, 2.44 +/- 0.66 microliter/min in the unaffected contralateral eyes, and 2.56 +/- 0.61 microliter/min in a group of 14 age-matched controls. A statistically significant difference (p < 0.05) in the aqueous flow rate was seen between the affected and unaffected eyes and between the affected and control eyes. Aqueous flow in the unaffected and control eyes was not statistically different. The anterior chamber volumes and intraocular pressures were also not significantly different among groups. Severe carotid artery disease may reduce aqueous humor formation by lowering ciliary body blood flow to a point beyond which the eye cannot compensate.

Aged↗

[The dependence of acid-base balance in the aqueous humor on carbon dioxide and oxygen diffusion through the cornea (author's transl)].

In 20 rabbits the effect of, gas exchange, between the aqueous humor and surrounding air through the cornea, on the acid-base balance in the aqueous was investigated. It was found that tight eye closure leads to a decrease of oxygen partial pressure in the aqueous humor. A concurrent displacement of the acid-base balance in the form of a mixed acidosis (respiratory and metabolic acidosis) was demonstrated.

Acid-Base Equilibrium↗

Acidosis, alkalosis, and aqueous humor dynamics in rabbits.

Systemic acidosis induced by intravenous administration of hydrochloric acid lowered intraocular pressure in unanesthetized rabbits. Aqueous humor flow was reduced by approximately 50%, as measured by the iodide method and as calculated from tonographic data. Outflow facility, episcleral venous pressure, plasma osmolality, blood pressure, pulse, and body temperature were not altered by systemic acidosis. Systemic alkalosis induced by intravenously administered sodium bicarbonate was associated with an increased intraocular pressure. Aqueous humor flow following systemic alkalosis was increased by approximately 100%, as measured by the iodide method and as calculated from tonographic data. Alkalosis was not associated with alterations in outflow facility, episcleral venous pressure, plasma osmality, blood pressure, pulse, or rectal temperature.

Acidosis↗

Non-secretion of mutant proteins of the glaucoma gene myocilin in cultured trabecular meshwork cells and in aqueous humor.

Until recently, very little was known about the molecular mechanisms responsible for the development of glaucoma, a leading cause of blindness worldwide. Mutations in the glaucoma gene myocilin (MYOC, GLC1A) are associated with elevated intraocular pressure and the development of autosomal dominant juvenile glaucoma and a subset of adult-onset glaucoma. MYOC is expressed in the trabecular meshwork (TM), a tissue responsible for drainage of aqueous humor from the eye, and the tissue involved in elevated intraocular pressure associated with glaucoma. To better understand the role of MYOC in glaucoma pathogenesis, we examined the expression of normal and mutant myocilin in cultured ocular (TM) and non-ocular cells as well as in the aqueous humor of patients with and without MYOC glaucoma. Normal myocilin was secreted from cultured cells, but very little to no myocilin was secreted from cells expressing five different mutant forms of MYOC. In addition, no mutant myocilin was detected in the aqueous humor of patients harboring a nonsense MYOC mutation (Q368X). Co-transfection of cultured cells with normal and mutant myocilin led to suppression of normal myocilin secretion. These studies suggest that MYOC glaucoma is due either to insufficient levels of secreted myocilin or to compromised TM cell function caused by congestion of the TM secretory pathway.

Animals↗

Aqueous humor flow and flare in patients with myotonic dystrophy.

PURPOSE: Myotonic dystrophy is an autosomal dominant form of muscular dystrophy associated with a mutation that affects a gene on chromosome 19. Extremely low intraocular pressure is one of a constellation of clinical signs that sometimes accompany this disorder. This study was performed to determine if the ocular hypotony can be explained by aqueous humor hyposecretion. METHODS: Seventeen persons with myotonic dystrophy and seventeen age-matched controls were studied. Intraocular pressure, light scattering (flare), fluorescein clearance at various times of day, and the response of the eye to the topical timolol were measured. RESULTS: Intraocular pressure was 40% lower in the persons with myotonic dystrophy (8.4 mm Hg vs 14.0 mm Hg) and flare was 50% higher (55.8 mg/dl albumin equivalent vs 37.1 mg/dl albumin equivalent). Fluorescein clearance in persons with myotonic dystrophy was indistinguishable from normal at all times of day. Myotonic eyes responded normally to topical timolol. The physiological data of this study are most consistent with the conclusion that the rate of aqueous humor flow is reduced approximately 9%, and the rate of inward leakage of light scattering proteins is increased approximately 37% in well-established myotonic dystrophy with ocular hypotony. CONCLUSIONS: The reduced aqueous humor flow alone is insufficient to explain the ocular hypotony. We hypothesize that the hypotony is due primarily to atrophy of the ciliary muscle that increases fluid exchange between the anterior chamber and the anterior uvea with consequent enhancement of uveoscleral outflow.

Administration, Topical↗