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Topically applied hydralazine: effects on systemic cardiovascular parameters, blood-aqueous barrier, and aqueous humor dynamics in normotensive humans.

Local application of hydralazine has been found to alter intraocular pressure in animal eyes. This study was undertaken to determine, in normotensive humans, the effects of topically-applied hydralazine on systemic cardiovascular parameters, blood-aqueous barrier, and aqueous humor flow. Two different concentrations of hydralazine were used: 0.03%, and 0.1%. Twenty healthy normotensive subjects were studied. Blood pressure, pulse rate, and intraocular pressure were measured every hour for six hours after hydralazine or placebo was instilled into the conjunctival sac in a double-masked, randomized fashion. With either hydralazine dose, there was no significant change in systemic blood pressure or pulse. In addition, spectrophotometrically-measured polarization of fluorescence and flare failed to show any significant breakdown of the blood-aqueous barrier. In most individuals, application of hydralazine was followed by a brief, mild to moderate, conjunctival hyperemic response. Compared to placebo at the same time of day, a small increase in intraocular pressure was observed with 0.03% hydralazine (p < .05). At 0.1%, this increase tended to be less. There was no statistically significant difference in aqueous humor flow between hydralazine-treated and placebo-treated eyes at the lower concentration (3.20 +/- 0.63 vs. 3.05 +/- 0.61 microL/min (mean +/- S.D.) or at the higher concentration (3.37 +/- 0.53 vs. 3.28 +/- 0.60 microL/min) of hydralazine. These results suggest that acute topical application of 0.1% hydralazine to the eyes of normal humans does not cause clinically significant cardiovascular effects or significant ocular toxicity.

Administration, Topical↗

The influence of Latanoprost 0.005% on aqueous humor flow and outflow facility in glaucoma patients: a double-masked placebo-controlled clinical study.

BACKGROUND: Fluorophotometry and pneumotonography were performed to investigate the effect of Latanoprost 0.005% and Placebo on aqueous humor flow and total outflow facility in human glaucomatous eyes. METHODS: In a randomized double-blind clinical study patients with POAG and OHT receive either Latanoprost 0.005% or placebo once in the evening. Fluorophotometry (Fluorotron Master II, Ocumetrics) and, Pneumotonography, Mentor) was performed in 20 eyes of 10 patients (verum) and 22 eyes of 11 patients (placebo). During a 2 week wash-out period all patients received a systemic antiglaucomatous therapy (Acetazolamide) up to 3 days before baseline measurement. Patients with IOP higher than 28 mmHg at baseline were excluded. Fluorophotometry, tonography and IOP were measured at baseline after 1 and 2 weeks of treatment. Data was analysed by the Student's paired t test. RESULTS: All patients completed the protocol. The IOP significantly decreased (25%) after 1 and 2 weeks of treatment with Latanoprost(p<0.01). Fluorophotometry measurements showed no difference in flow over time in both groups. Although tonographic mean C values in both groups did not show any difference over time, the estimated total outflow facility C (Goldmann) increased significantly (p<0.05) in the verum-treated eyes after 2 weeks. A significant difference of outflow co-efficient correlated to normal pressure (P0/C) was found after 2 weeks of treatment with Latanoprost (p<0.05). CONCLUSIONS: In accordance with the literature we found a mean 25% decrease in IOP after 2 weeks of treatment with Latanoprost 0.005%. The analysis of the flow values in both groups showed no increase or decrease in aqueous humor dynamics as proved in many previous studies. The known effect of Latanoprost increase uveoscleral outflow by remodeling extracellular matrix and widening intermuscular spaces in the ciliary body may not detected by pneumotonography after 2 weeks of treatment. The significant increase in estimated total outflow facility (Goldmann formula) in latanoprost-treated eyes and the decrease of IOP took place at constant flow rates. The increase in conventional outflow facility may indicate trabecular meshwork changes, but it cannot explain the significant decrease in IOP. Furthermore, an additional effect, e.g. uveoscleral outflow, may play the major role as considered in many previous studies.

Adult↗

Nonspecific immunoglobulin E in aqueous humor: evaluation in uveitis.

The levels of immunoglobulin E (IgE) in aqueous humor (AH) and serum were determined in 74 uveitis patients and 13 control patients with senile cataract. Uveitis patients' levels ranged from less than 0.06 to 460 IU/ml according to the paper radioimmunosorbent test (PRIST; limit of sensitivity, 0.06 IU/ml). Only one control patient had an AH level higher than the sensitivity limit (0.08 IU/ml). Of the five patients with the highest levels in the AH, four had toxocaral retinitis. The ratio of AH/serum to IgE normalized to the albumin concentration was calculated in 25 uveitis patients and was greater than 0.60 in 13 cases, indicating a possible intraocular IgE synthesis.

Adolescent↗

The effect of acetyl-salicylic-acid pretreatment on re-formed aqueous humor. A study of intracapsular lens extraction in the human eye.

Aqueous humor (a.h.) was sampled in 67 patients operated on for cataract by intracapsular lens extraction at the start and finish of surgery. Twenty eight of these patients received pretreatment with acetyl-salicylic acid (ASA), to a total of 2.5 g, beginning 18 hours prior to surgery. A serum sample was drawn immediately following the operation from 55 patients. Using radial immunodiffusion, albumin and IgG were measured in primary and secondary a.h. and in serum. The group pretreated with ASA showed a significantly smaller relative increase of IgG (P < 0.05). The increase of the proteins, however, showed no dependence on their serum-level and the only side-effect of the treatment was an unexplained rise in serum-albumin. The possible clinical application of patients with a high risk of postoperative complications is briefly summarized.

Aqueous Humor↗

Secondary aqueous humor stimulates the proliferation of cultured bovine corneal endothelial cells.

Secondary aqueous humor (2 degrees AH) is known to contain elevated levels of serum macromolecules and has been shown to stimulate the proliferation of lens epithelial cells both in vivo and in vitro as well as corneal endothelial cells in vitro. The purpose of this study was to characterize the response of bovine corneal endothelial cells to 2 degrees AH from rabbits and to compare the effect when the cells were grown on plastic dishes covered with an extracellular matrix or on plastic alone. The addition of varying amounts of 2 degrees AH protein (0.1 to 10 mg/ml) to bovine corneal endothelial cells (cultured in MEM plus 1% serum) resulted in a dose dependent proliferative response as measured by the incorporation of 3H-thymidine into DNA. Except for a 2-hr lag phase, the proliferative response increased with increasing time of exposure (6-18 hrs) of the cells to 2 degrees AH containing a constant amount (2.0 mg/ml) of protein. The generation time and final density of the cells, but not the plating efficiency, was significantly greater when the cells were grown in the presence of 2 degrees AH protein on an extracellular matrix rather than plastic alone. Selective adsorption of prostaglandins and aromatic compounds from 2 degrees AH reduced its ability to produce a proliferative response to control levels. These results indicate that 2 degrees AH can alter or regulate events in the cell cycle of corneal endothelial cells. The responsible factor(s) could be involved in control of cellular regeneration in the eye following injury.

Animals↗

Ascorbic acid concentration is reduced in the aqueous humor of patients with exfoliation syndrome.

PURPOSE: To investigate whether there is a role for ascorbic acid in the development of exfoliation syndrome (XFS). DESIGN: A case-control study was undertaken that included consecutive patients with and without XFS in whom cataract surgery was indicated. Patients with ophthalmic conditions other than XFS and conditions that may influence ascorbic acid levels were excluded. METHODS: A prospective institutional study was undertaken. A small volume of aqueous humor was aspirated at the beginning of phacoemulsification cataract surgery. Eighty aqueous samples, 40 samples from 40 eyes of 40 cataract patients with XFS and 40 samples from 40 eyes of 40 age matched cataract patients without XFS, were collected and analyzed. Ascorbic acid concentration was evaluated in the aqueous samples with a microplate assay method. RESULTS: The mean +/- SD concentration of ascorbic acid in the aqueous from patients with XFS (0.86 +/- 0.43 mM; range, 0.12 to 1.7 mM) was significantly lower than the concentration of ascorbic acid found in the aqueous of age-matched control patients (1.15 +/- 0.50 mM; range 0.42 to 3.1 mM; P =.0068). Total mean protein concentration was found to be significantly higher in the XFS group (481.1 +/- 196.8 pg/dl versus 336.3 +/- 86.4 pg/dl in the controls; P <.0001). Nevertheless, no correlation could be established between ascorbic level and protein concentration. CONCLUSIONS: A significantly reduced mean level of ascorbic acid was observed in the aqueous humor of patients with XFS. In view of the fact that ascorbic acid is a major protective factor against free radical action, a role for free radical action is possible in the pathobiology of XFS.

Aged↗

Aqueous humor analysis as a diagnostic tool in toxoplasma uveitis.

Analysis of local toxoplasma antibody production to confirm a suspected clinical diagnosis of toxoplasma chorioretinitis is a valuable diagnostic tool. Determination of toxoplasma antibodies in the blood of the patient is of limited use. When blood toxoplasma tests are negative this indicates that toxoplasma as a causative organisms in the pathogenesis of uveitis is unlikely. A positive blood test is a sensitive test (100% patients positive) but not a specific test since so many healthy individuals already have undergone subclinical infection and have acquired humoral immunity against the parasite. We analysed 93 paired aqueous and serum samples for toxoplasma antibodies and total IgG and determined the Goldmann-Wittmer coefficient. In patients retrospectively diagnosed as having toxoplasma chorioretinitis 16 out of 22 had a positive coefficient, indicating local parasite antibody production. In one patient with AIDS we also found a positive toxoplasma coefficient. Three out of 15 patients with posterior uveitis of unknown origin also had a positive coefficient. None of the cataract patients tested (n = 32) had a positive coefficient. Major drawbacks of aqueous humor analysis are that a false negative antibody coefficient can occur when a massive blood aqueous barrier breakdown has occurred.

Antibodies, Protozoan↗

The effect of levobunolol on aqueous humor dynamics.

We evaluated the acute effects of installation of 0.5% levobunolol on aqueous humor dynamics in a double-masked study in 18 patients with ocular hypertension. Aqueous flow was measured by fluorophotometry and total outflow facility by tonography. Aqueous flow decreased approximately 29% in the eyes treated with levobunolol. Total outflow facility and episcleral venous pressure measurements were similar in levobunolol-treated eyes and contralateral eyes treated with vehicle. A 36% decrease in intraocular pressure was observed in the levobunolol-treated eyes and a slight intraocular pressure reduction was seen in the vehicle-treated eyes. The results of this study indicate that, similar to timolol, levobunolol lowers intraocular pressure primarily by decreasing aqueous humour production.

Adrenergic beta-Antagonists↗

[Intraocular penetration of pefloxacin in man and rabbit. The aqueous humor and vitreous body].

Intraocular distribution of pefloxacin was evaluated in 64 patients undergoing ocular surgery and in 4 rabbits after experimental infection of one eye by Staphylococcus aureus. Patients were perfused during one hour either with 800 or 400 mg of pefloxacin. Samples (serum, aqueous humor, vitreous fluid) were collected 0, 1, 2, 3, 4, 5 or 12 h after the end of antibiotic administration. Antibiotic levels were measured using a standard microbiological assay. The aqueous humor levels remained stables until 12 h, but were higher with a posology of 800 mg (mean level: 2.66 mg/l) than with a posology of 400 mg (mean level: 0.66 mg/l). The ratio between vitreous and serum concentrations ranged from 8 at 12% with 400 mg and from 2 to 36% with perfusion of 800 mg. The efficacy of pefloxacin treatment is demonstrated in the experimental infection of rabbits eyes.

Adult↗

Different concentrations of vasoactive intestinal polypeptide in aqueous humor of patients with proliferative vitreoretinopathy and cataract patients.

The pathophysiological events leading to cellular proliferation in proliferative vitreoretinopathy are largely unknown. An involvement of neuropeptides in that disease has recently been discussed, as substance P was found to be highly enriched in the intraocular fluid of patients with proliferative vitreoretinopathy. In the present study, aqueous humor was analyzed for another neuropeptide, vasoactive intestinal polypeptide. Radioimmunoassay revealed significantly increased levels of that polypeptide in the aqueous humor of patients with proliferative vitreoretinopathy as compared with cataract patients who served as controls. As vasoactive intestinal polypeptide contributes to the environment of the retinal pigment epithelial cell layer and induces proliferation of these cells in vitro, this peptide may be involved in the pathogenetic mechanisms leading to cellular proliferation in proliferative vitreoretinopathy.

Aqueous Humor↗

Penetration of parenteral cefuroxime into the human aqueous humor.

Concentrations of (6R-[6 alpha,7 beta(Z)])-3-([(amino-carbonyl)oxy]metyl)-7-([2-furanyl(methoxyimino)-acethyl] amino)-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carbonic acid (cefuroxime) were studied in blood and aqueous humor of 25 patients after various parenteral doses. lows: 1 h after a single 2 g i.v. dose; 1 h after the second of 2 1.v. doses of 2 g at an interval of 3 h; 6 h after a 2-g i.v. dose; 1 h after a 1.5-g i.m. dose; 1 h after the second of 2 i.m. doses of 1.5 g at an interval of 3 h. The highest levels of cefuroxime in blood (18.1 +/- 2.79 micrograms/ml) and in aqueous humor (4.1 +/- 1.98 micrograms/ml) were reached 1 h after the second administration of a 1.5-g i.m. dose.

Aged↗

Quantification of nitric oxide and cytokines in rabbit aqueous humor after neodymium:YAG laser capsulotomy.

PURPOSE: The purpose of this study was to evaluate the presence of nitric oxide (NO) and cytokines such as interleukin 1 beta, interleukin 2 receptor (IL-2R), interleukin 6 and tumor necrosis factor alpha on aqueous humor after neodymium:YAG (Nd:YAG) laser posterior capsulotomy. METHODS: Fifteen rabbits (30 eyes) with dense posterior capsule opacities underwent Nd:YAG capsulotomy 4 months after phacoemulsification cataract surgery. After general and topical anesthesia, Nd:YAG capsulotomy was performed using an equal number of shots and power setting on all eyes. Aqueous humor specimens were collected from each eye preoperatively and at 12, 24 and 48 h after the surgery to determine NO and cytokine levels. RESULTS: The levels of NO and cytokines except IL-2R were significantly high as compared to preoperative levels in all eyes at 12 and 24 h postoperatively (p < 0.05). Although the levels of NO and cytokines were higher than preoperative levels at 48 h, the differences were not statistically significant (p > 0.05). CONCLUSION: These findings suggest that NO and cytokines appear to be potential inflammatory mediators in the occurrence of early inflammation following Nd:YAG posterior capsulotomy.

Animals↗

Aqueous humor cyclic AMP and circadian elevation of intraocular pressure in rabbits.

Rabbits entrained in a daily light-dark environment show a circadian elevation of intraocular pressure (IOP) around the onset of dark. It was reported that concentration of cyclic AMP (cAMP) in aqueous humor increases significantly during this time period. Whether or not the increase of ocular cAMP-mediated activities is related to the circadian elevation of IOP is unclear. Light-dark entrained rabbits maintain the circadian IOP elevation in a constant dark environment. Corresponding to this IOP elevation in the constant dark, no change of aqueous humor cAMP concentration was found. Thus, the circadian IOP elevation in the constant dark is probably unrelated to the cAMP-mediated activities. This finding also suggests that a significant portion of the circadian IOP elevation in the light-dark environment is unrelated to the cAMP-mediated activities.

Animals↗

[Neuron-specific enolase in the aqueous humor. Its significance in the differential diagnosis of retinoblastoma].

Several studies support that retinoblastoma originates from a primitive neuroectodermal cell, the main argument being the expression of the neuron-specific enolase (NSE) by the retinoblastic cells. NSE was measured in the aqueous humor taken off: 1) in 19 patients with various eye disorders for which the diagnosis of retinoblastoma was definitely excluded (NSE = 5.0 +/- 7.7 micrograms/l); 2) at the time of the enucleation, in 7 cases of proved retinoblastoma (NSE = 83 to 17,900 micrograms/l); 3) in 2 cases of retinoblastoma held as cured for more than 5 years (NSE = 2.8 and 8.7 micrograms/l). The high level of NSE in the aqueous humor of the subjects with retinoblastoma is very significant, so that it can play a great part in the diagnosis, particularly in the case of atypic tumors. Specific indications of this determination may be considered for the survey of tumors under treatment or of the controlateral eye after a first tumor.

Aqueous Humor↗

[Glaucoma related with photoreceptor outer segments in aqueous humor. Schwartz-Matsuo syndrome].

CASE REPORT: We present the case of a patient who was initially diagnosed of hypertensive uveitis with marked fluctuation that was resistant to the common treatment. After a systematic examination, retinal detachment of the ora serrata in the inferotemporal quadrant was diagnosed. The sample of aqueous humor showed melanic pigment and degenerated photoreceptor outer segments. After retinal detachment surgery, the intraocular pressure returned to normal levels without antiglaucoma medication. DISCUSSION: The presence of photoreceptor outer segments in aqueous humor confirms the diagnosis of Schwartz-Matsuo syndrome, which should be considered as a differential diagnosis of iritis and glaucoma.

Adult↗