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A method for near-continuous determination of aqueous humor flow; effects of anaesthetics, temperature and indomethacin.

A method is described for near-continuous determination of aqueous humor flow. The anterior chamber is perfused with push-pull coupled syringes at a low rate with a fluid containing labelled albumin. An external circuit is used to determine continuously the anterior chamber concentration of the labelled protein. The dilution data are analysed on-line by a minicomputer which permits rapid calculation of the anterior chamber volume and the rate of flow of aqueous humor. The technique and some experiments of technical interest are reported. Experiments in monkeys with different anaesthetics resulted in flow values of 0.99 +/- 0.02, 1.47 +/- 0.09 and 0.99 +/- 0.04 microliter min-1 for pentobarbital, urethane and ketamine anaesthesia, respectively. By using 125I-labelled albumin in one eye and 131I-labelled albumin in the other, it was possible to determine flow in both eyes. Highly significant correlation coefficients between the two sides were found for the rate of aqueous flow, intraocular pressure and anterior chamber volume. Rapid changes in inflow into the anterior chamber from the posterior chamber were produced by elevating and then lowering the intraocular pressure; the delay inherent in the method was about 6 min. Indomethacin, 3 mg kg-1 body wt., had no effect on aqueous humor flow in eyes cannulated with a minimum of trauma. In eyes with problematic cannulation indomethacin at this dose tended to delay an irritation response. Changes in temperature of the fluid perfused through the anterior chamber had no clear effect on the rate of aqueous flow. Warming the animals about 3-4 degrees C above the normal temperature tended to increase the rate of aqueous flow. Cooling by 3-4 degrees C had no clear effect. Cooling after an initial warming also had no clear effect. The rate of flow of aqueous humor from the anterior chamber to the general circulation was calculated from data for the accumulation of labelled albumin in the general circulation. The difference between the rate of aqueous flow determined from the dilution data and the flow into blood was assumed to represent uveoscleral flow. In 14 animals with an aqueous flow of 1.19 +/- 0.08 microliters min-1 the flow to the general circulation was 0.57 +/- 0.055 and uveoscleral flow 0.61 +/- 0.09 microliters min-1. The procedure and mathematical treatment will be applicable to flow determinations with other large molecules and in other systems.

Anesthetics↗

[Levels of antiphospholipid antibodies in the serum and aqueous humor of glaucoma patients].

PURPOSE: Evaluation of antiphospholipid antibodies in the serum and aqueous humor in patients with glaucoma. MATERIAL AND METHODS: 48 persons (38 women and 17 men), aged 30-86 (mean age 70), suffering from glaucoma was examined. There were 19 with POAG, 18 with PACG and 11 with PEXG. All patients have undergone trabeculectomia. The group of 20 operated, because of age-related cataracta patients (7 men and 13 women), aged 47-82 (mean age 65) constituted a control group. All patients agreed to samples collection. In plasma and anterior chamber fluid the level of antiphospholipids antibodies classes IgM and IgG were measured, using ELISA method (commercial kits produced by Euroimmun) according to producent's instruction. Statistical analysis was performed using U Mann-Whitney test. RESULTS: The mean values of antiphospholipids in both group are put in the table. The significant differences between glaucoma and no-glaucoma patients were observed in levels of IgG in serum (p=0.014) and in levels of IgM antibodies in aqueous humor (p=0.013). CONCLUSIONS: The presence of elevated levels of antiphospholipid antibodies in aqueous humor and serum may be a risk factor in progression of glaucomatous neuropathy.

Adult↗

Tissue plasminogen activator activity in human aqueous humor.

PURPOSE: To determine the levels of free plasminogen activator activity in human aqueous humor and to identify the type of activity (i.e., tissue-type t-PA or urokinase-type u-PA) that is responsible. METHODS: Aqueous humor was obtained by a simplified pipette paracentesis before cataract surgery in 31 subjects, ages 57 to 93 years. Levels of plasminogen activator activity were determined using a modified 17-hour specific amidolytic assay. The type of plasminogen activator was investigated in selected samples based on its dependence on soluble fibrin, inhibition by amiloride, and specific antibody blocking. Activity-antigen ratios were compared in seven samples. RESULTS: Plasminogen activator (PA) activity was present in all samples tested. PA activity ranged widely between 0.54 and 26.7 mIU/ml, with a mean value of 10.8 +/- 8.1 mIU/ml. Soluble fibrin, a known stimulator of tissue-type plasminogen activator (t-PA), was required in the assay system. Its absence decreased the measured activity by more than 90%. Amiloride, a known inhibitor of urokinase-type PA, had little or no effect in selected samples tested. The activity was blocked by anti-human t-PA antibodies but not by antibodies against human u-PA, further defining the type of PA responsible for the detected activity. t-PA antigen levels showed less variation among individuals than did activity levels. Antigen-activity ratios ranged between 89 and 552. CONCLUSION: Plasminogen activator activity is present in the human aqueous humor in measurable quantities. The type of PA activity present is almost exclusively t-PA. t-PA activity varies more widely than antigen, as is the case in plasma.

Aged↗

Effect of UV-A and UV-B irradiation on the metabolic profile of aqueous humor in rabbits analyzed by 1H NMR spectroscopy.

PURPOSE: This study was conducted to investigate metabolic changes in aqueous humor from rabbit eyes exposed to either UV-A or -B radiation, by using (1)H nuclear magnetic resonance (NMR) spectroscopy and unsupervised pattern recognition METHODS: methods. Both eyes of adult albino rabbits were irradiated with UV-A (366 nm, 0.589 J/cm(2)) or UV-B (312 nm, 1.667 J/cm(2)) radiation for 8 minutes, once a day for 5 days. Three days after the last irradiation, samples of aqueous humor were aspirated, and the metabolic profiles analyzed with (1)H NMR spectroscopy. The metabolic concentrations in the exposed and control materials were statistically analyzed and compared, with multivariate methods and one-way ANOVA. RESULTS: UV-B radiation caused statistically significant alterations of betaine, glucose, ascorbate, valine, isoleucine, and formate in the rabbit aqueous humor. By using principal component analysis, the UV-B-irradiated samples were clearly separated from the UV-A-irradiated samples and the control group. No significant metabolic changes were detected in UV-A-irradiated samples. CONCLUSIONS: This study demonstrates the potential of using unsupervised pattern recognition methods to extract valuable metabolic information from complex (1)H NMR spectra. UV-B irradiation of rabbit eyes led to significant metabolic changes in the aqueous humor detected 3 days after the last exposure.

Amino Acids↗

5 alpha-dihydrocortisol in human aqueous humor and metabolism of cortisol by human lenses in vitro.

Glucocorticoids have long been implicated in the etiology of primary open-angle glaucoma (POAG) and cataract. Cortisol metabolites have biologic activity and may affect aqueous humor dynamics. This study was done to determine whether these metabolites are found in human aqueous humor and can be produced by ocular tissues. Radioimmunoassays (RIA) were developed for 5 alpha-dihydrocortisol (5 alpha-DHF) and 5 beta-dihydrocortisol (5 beta-DHF). These assays, as well as a cortisol RIA, were used to quantify these three steroids in 20 surgically derived aqueous humor specimens from patients with and without POAG. The mean concentrations of cortisol and 5 alpha-DHF were 2.5 and 1.3 ng/ml, respectively. In the small group studied, there was no statistically significant difference between the aqueous humor steroid levels in patients with and without POAG. The amount of 5 beta-DHF was at the lower limits of detection of the assay system and could not be uniquivocally shown. Human lenses metabolized cortisol in vitro to 5 alpha-DHF and 3 alpha,5 alpha-tetrahydrocortisol (3 alpha,5 alpha-THF). There was no 5 beta-DHF or cortisone formed. The 5 alpha-DHF and 3 alpha,5 alpha-THF were identified by their positions on thin-layer chromatography, their retention times on high-performance liquid chromatography, and recrystallization with authentic standards to constant specific activity. The data suggest that the lens is the source of 5 alpha-DHF in aqueous humor.

Aged↗

[1,3,7-trimethylxanthine. Effects on circadian aqueous humor dynamics in probands].

Anterior chamber fluorophotometry (Fluorotron Master II, Coherent, Palo Alto, Calif.) was used to investigate the influence of 1,3,7-trimethylxanthin on the circadian rhythm of aqueous humor secretion in two age-, race- and sex-matched groups of healthy volunteers. In ten males and ten females (mean age 27 years), aqueous humor secretion was measured over 24 h at: 0800, 0900, 1000-1400, 1500, 1600-2000, 2100, 2200-0200, 0300, and 0400 hours. Flow was calculated using the Yablonsky protocol of Fluorotron Master II. In group I all volunteers received about 800 mg trimethylxanthin in the form of caffeinated coffee between 2200 and 2300 hours. In group II volunteers went to sleep at 2300 hours. Sleep was only interrupted for measurements. During the daytime the mean aqueous humor flow was the same in both groups (0800 to 2200 hours) (Student's t-test): Group I (n = 10) RA 2.27 +/- 0.70 microliters/min LA 2.25 +/- 0.74 microliters/min Group II (n = 10) RA 2.23 +/- 0.73 microliters/min LA 2.06 +/- 0.64 microliters/min During the night the mean aqueous humor flow decreased in both groups (0200 to 0400 hours): Group I: RA 1.99 +/- 0.74 microliters/min delta flow = -12% LA 1.93 +/- 0.75 microliters/min Group II: RA 0.97 +/- 0.50 microliters/min delta flow = -56% LA 0.97 +/- 0.48 microliters/min The difference between groups was statistically significant (P = 0.01, t-test for unpaired samples). There was no significant change in mean aqueous humor flow between the daytime vs night in group I (P < 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Circadian variations of prostaglandins in the rabbit aqueous humor.

Forty-eight young adult New Zealand albino rabbits were entrained to a daily 12-hr light and 12-hr dark cycle. Under a constant dark environment, rabbits were sacrificed at 4-hr intervals, beginning at 2 hr before the accustomed lights-on period. Eight rabbits were used for each of the 6 time points within 24 hr. Aqueous humor and vitreous humor samples were collected. Samples from one eye of each rabbit were assayed for prostaglandins D2, E2, and F2alpha by enzyme immunoassay. Total protein concentrations in the samples were also determined. Concentrations of prostaglandins D2 and F2alpha in the aqueous humor were found to vary in a consistent pattern. The prostaglandin F2alpha concentration increased in the early subjective light period, remained high in this period, and decreased in the subjective dark period. The prostaglandin D2 concentration was elevated only in the early subjective light period. No significant change of aqueous humor prostaglandin E2 level was found. Total protein concentration in the aqueous humor varied in a similar pattern as the aqueous humor prostaglandin F2alpha, indicating a close association between the permeability of protein across the blood-aqueous barrier and the endogenous prostaglandin F2alpha level. In the vitreous humor, concentrations of all three prostaglandin subtypes remained unchanged, as did the total protein concentration. However, vitreous humor concentrations of prostaglandin D2 and F2alpha were significantly higher than their concentrations in the aqueous humor.

Animals↗

[Lens crystallin leakage in aqueous humor from human cataractous lenses].

The amounts of human lens crystallins in the aqueous humor from various types of cataract patients were measured by radioimmunoassay. alpha, beta and gamma-crystallins as antigens for radioimmunoassay were purified from one-year-old normal human lens by TSK3000SW gel permeation column using high performance liquid chromatography. The amounts of both alpha- and gamma-crystallin in the aqueous humor from the patients with cortical and posterior subcapsular cataract were relatively low but in the case of mature cataract those of both crystallins increased. While the amounts of beta-crystallin in aqueous humor from cortical and posterior subcapsular cataract patients were at the same level compared with alpha-crystallin, those from mature cataract patients showed extremely high values.

Aged↗

Silver staining of human aqueous humor proteins resolved by gel electrophoresis.

The detection of aqueous humor proteins resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was achieved using an ultrasensitive silver staining technique. This procedure permitted the detection of more than 35 different protein bands in human aqueous humor on a one-dimensional gel. Most of the stained proteins had an apparent molecular weight greater than 45,000 daltons.

Aqueous Humor↗

Penetration of topically applied ciprofloxacin and ofloxacin into the aqueous humor and vitreous.

PURPOSE: To determine the intraocular penetration of topical drops of 2 antibiotics, ciprofloxacin 0.3% and ofloxacin 0.3%, into the aqueous humor and vitreous and to relate these levels to the miminum inhibitory concentration (MIC(90)) for organisms associated with ocular bacterial infections. SETTING: Department of Ophthalmology, Ankara Hospital, and Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. METHODS: This prospective randomized clinical trial comprised 18 patients having cataract surgery, all with an intact corneal epithelium. The patients were randomly assigned to receive topical ciprofloxacin 0.3% (n = 10) or topical ofloxacin 0.3% (n = 8) 1 drop every 15 minutes 5 times and every 30 minutes 3 times before surgery. Aqueous and vitreous samples (if vitreous loss occurred during the cataract surgery) were collected 30 minutes after the administration of the last dose. Drug concentrations were determined by high-performance liquid chromatography (HPLC) fluorescence. RESULTS: All patients had detectable drug concentrations in the aqueous humor and vitreous measurable by HPLC. The mean aqueous humor concentration of ciprofloxacin was 1.13 microg/mL +/- 1.90 (SD) and the mean vitreous concentration, 0.23 +/- 0.06 microg/mL. Topical administration of ciprofloxacin yielded 4.9 times more drug concentration in the anterior chamber than in the vitreous. The mean aqueous concentration of ofloxacin was 2.06 +/- 1.06 microg/mL and the mean vitreous concentration, 0.46 +/- 0.10 microg/mL. Topical administration of ofloxacin yielded 4.7 times more drug concentration in the anterior chamber than in the vitreous. Aqueous humor concentrations of ofloxacin and ciprofloxacin were not statistically significantly different (P =.353). Intravitreal concentrations of ofloxacin were statistically significantly higher than those of ciprofloxacin (P =.001). CONCLUSIONS: Topical ofloxacin 0.3% penetrated better than topical ciprofloxacin 0.3% into the anterior chamber and vitreous in noninflamed eyes. Both drugs were above the MIC(90) for most ocular pathogens in the anterior chamber. The mean concentration in the vitreous of topically applied ofloxacin 0.3% was statistically significantly higher than that of ciprofloxacin 0.3%, but it was not sufficiently above the MIC(90) for most ocular pathogens in terms of empirical endopthalmitis therapy.

Administration, Topical↗

Postoperative fluctuations of tissue plasminogen activator (t-PA) in aqueous humor of pseudophakes.

We studied the quantitative fluctuations of tissue plasminogen activator (t-PA) activity and antigen in aqueous humor before and after extracapsular cataract extraction and poly(methyl methacrylate) posterior chamber lens implantation. The t-PA activity level was measured by solid phase bioimmunoassay using monoclonal antibody against an epitope apart from the active site of t-PA, and the antigen by ELISA. In our patients the mean preoperative level of t-PA activity was 0.0664 +/- 0.0472 IU/ml (mean +/- SD) and of the antigen, 0.175 +/- 0.024 ng/ml. The t-PA activity level in aqueous humor was markedly decreased on the first postoperative day (0.0042 +/- 0.0037 IU/ml), recovered on the second day (0.0403 +/- 0.0251 IU/ml), and then progressively decreased from the fourth to the seventh days. The t-PA antigen level in aqueous humor increased on the first (0.366 +/- 0.108 ng/ml) and second (0.403 +/- 0.251 ng/ml) postoperative days and gradually decreased from the fourth to seventh days. Under the intracameral condition of the fibrinolytic system, various factors, e.g., serious inflammation or events affecting the balance of coagulation and fibrinolysis, may induce the decrease or depletion of t-PA activity, followed by the pupillary fibrin membrane formation. We suggest that fluctuations of t-PA activity in aqueous humor may affect fibrinous membrane formation over the IOL surface.

Aged↗

[Quantification of basic fibroblast growth factor (bFGF) and transforming growth factor (TGF alpha) in rabbit aqueous humor after intraocular lens implantation].

Basic fibroblast growth factor (bFGF) and transforming growth factor alpha (TGF alpha) in rabbit aqueous humor were quantified before and after phacoemulsification (phaco) and intraocular lens (IOL) implantation by enzyme linked immunosorbent assay (ELISA). bFGF was not detected (< 10 pg/ml) before the operation, but increased to 250 +/- 150 pg/ml in a phaco group and 300 +/- 280 pg/ml in a phaco+IOL group on the first postoperative day. The concentration of bFGF in the aqueous humor was the highest in the first postoperative week, with a peak value of 390 +/- 180 pg/ml, and then gradually decreased to 130 +/- 50 pg/ml in the phaco group and 180 +/- 160 pg/ml in the phaco+IOL group in the eighth postoperative week. TGF alpha was not detected (< 10 pg/ml) before the operation or on the first postoperative day in either group. 25 +/- 50 pg/ml and 35 +/- 100 pg/ml of TGF alpha was detected in a phaco group and a phaco+IOL group on the third postoperative day and then TGF alpha in the aqueous humor gradually decreased becoming undetectable in the third postoperative week. The level of bFGF and TGF alpha was higher in a phaco+IOL group than in a phaco group but there was no statistical significance. The results show that bFGF increases in the aqueous humor for several postoperative weeks and suggests that it is one the of factors that promote capsular opacities and shrinkage in the early postoperative period of cataract extraction.

Animals↗

Effects of Al3+ and Be2+ ions combined with NaF on ciliary process adenylyl cyclase activity and aqueous humor dynamics in the rabbit eye.

PURPOSE: The activity of Al3+, Ga3+, and Be2+ ions in the presence of NaF to directly activate G-proteins was investigated by their potentiative effect on forskolin (FSK)-activated adenylyl cyclase in rabbit ciliary process membranes and their effects on aqueous humor dynamics in vivo. METHODS: Adenylyl cyclase (AC) was determined by radiometric conversion of ATP to cAMP by the particulate fraction of rabbit ciliary processes. Intravitreal injections of sterile solutions of analytical grade salts were made into the center of the vitreous in a volume of 20 microliters. Intraocular pressure, aqueous humor flow, and uveoscleral outflow measurements were made by pneumatonometry, fluorophotometry, and fluorescein-dextran method, respectively. Outflow facility was determined by tonography in the intact eyes and by two-level constant pressure perfusion in cannulated eyes. RESULTS: Both Al3+ (EC50, 40 mumol/l) and Be2+ (EC50, 11 mumol/l) in the presence of 0.5-2 mM NaF activated the stimulatory G-protein Gs. Ga3+ was ineffective and did not antagonize the activation by Al3+. Intravitreal injections of Al3+ (1 mumol/eye) or Be2+ (0.5 or 1 mumol/eye) had no significant intraocular pressure (IOP) effect, nor did 1.5 or 3 mumol/eye of NaF, but when either cation was injected together with NaF, IOP decreased by up to 40% for up to 140 hr. At the time of maximum IOP effect (72 hr) aqueous humor flow determined by fluorophotometry was decreased in BeCl2+ NaF-treated eyes by 40% relative to BeCl2-treated eyes; however, tonographic facility of outflow was unaffected. Uveoscleral flow was also decreased by 38% in BeCl2+ NaF treated eyes. CONCLUSIONS: These findings support the hypothesis that Gs activation of ciliary process adenylyl cyclase decreases aqueous humor formation rate in rabbit eyes, and that activation of G-proteins mediates contraction of ciliary muscles causing a decrease of aqueous humor outflow via the uveoscleral route. The results suggest that G-proteins putatively involved in trabecular facility changes are less sensitive to activation by BeF3- than are other parameters of aqueous humor dynamics.

Adenylyl Cyclases↗

Increased interleukin-6 in aqueous humor of neovascular glaucoma.

PURPOSE: To demonstrate the involvement of proinflammatory cytokines in intraocular neovascularization by detecting the presence of interleukin (IL)-6, IL-2, and tumor necrosis factor (TNF)-alpha in aqueous humor and serum of patients with neovascular glaucoma (NVG) secondary to central retinal vein occlusion (CRVO). METHODS: According to the grade of iris neovascularization (NVI), patients with CRVO were divided into three groups: CRVO without NVI, CRVO with NVI, and CRVO with regressed NVI. Healthy patients with cataract were enrolled as control subjects. Enzyme-linked immunosorbent assay was used to quantitate the concentrations of the cytokines IL-6, IL-2, and TNF-alpha in aqueous humor and serum from patients with NVG and control subjects. RESULTS: In serum, the levels of IL-6, IL-2, and TNF-alpha did not differ among groups. In aqueous humor, only IL-6 showed significant change among groups. IL-6 levels in aqueous humor of group 2, CRVO with NVI (1532.0+/-221.1 pg/ml; P < 0.001), and group 3, CRVO with regressed NVI (234+/-154.6 pg/ml; P < 0.001), were significantly higher. There was no significant difference in IL-6 levels between the control group (26.4+/-21.8 pg/ml) and group 1 (15.6+/-0.9 pg/ml). CONCLUSIONS: The inflammatory cytokine IL-6 in aqueous humor increased spatially and temporally correlated with the grade of NVI in patients of NVG secondary to CRVO. The aqueous IL-6 increased in NVI and decreased after vessels regressed. It is possible that the significantly higher level of IL-6 was due to intraocular synthesis because of the minimal change in serum. The increased level of IL-6 may have a putative role along with other angiogenic factors in angiogenesis of NVG as a possible predictor of NVI.

Aged↗

The effect of intraoperative antibiotics in irrigating solutions on aqueous humor contamination and endophthalmitis after phacoemulsification surgery.

PURPOSE: To determine the efficacy of intraoperative antibiotic use in irrigating solutions on aqueous humor contamination during phacoemulsification surgery and to evaluate the corresponding risk of postoperative endophthalmitis. METHODS: 644 eyes of 640 patients who underwent phacoemulsification surgery with foldable intraocular lens (IOL) implantation were included in this study. Preoperative conjunctival smears were taken and eyes were allocated to receive irrigating infusion fluid containing either balanced salt solution (BSS)-only (group 1; 322 eyes) or BSS with antibiotics (vancomycin and gentamycin) during surgery (group 2; 322 eyes). Bacterial contamination rates of aqueous humor samples taken in the beginning and at the end of operation were compared. Predictive factors for the development of postoperative endophthalmitis were determined by clinical and microbiologic analyses. RESULTS: The rates of culture-positivity were similar between group 1 and group 2 for both preoperative conjunctival smears and aqueous samples (p > 0.05). Aqueous samples taken at the end of operation were found to be contaminated in 68 (21.1%) eyes in group 1 and 22 (6.8%) eyes in group 2, and the difference was significant (p = 0.0001; OR = 3.65 (2.1-6.0)). Capsular rupture was associated with higher rate of contamination in both groups (p = 0.0001; OR = 7.7 and p = 0.0001; OR = 8.1). Two eyes in the BSS-only group developed postoperative endophthalmitis and these cases had posterior capsular rupture during the surgery and culture-positivity for staphylococcus epidermidis throughout the study. CONCLUSIONS: Intraoperative antibiotic irrigation decreases aqueous humor contamination during phacoemulsification. Further studies are warranted to determine the interrelationship between aqueous humor contamination and endophthalmitis in eyes with posterior capsular rupture.

Acetates↗

UV absorption by uric acid in diurnal bird aqueous humor.

PURPOSE: To analyze the components responsible for the UV absorbance in diurnal bird aqueous humor. METHODS: The absorbance studies were carried out using a Hitachi spectrophotometer (U 2000). Uric acid was determined by high-performance liquid chromatography (LC-10 system; Shimadzu, Kyoto, Japan). Chicken and turkey eyes were examined. RESULTS: The UV absorbance in chicken aqueous was largely accounted for by the presence of protein, tryptophan, tyrosine, ascorbic acid, and uric acid. Ascorbic acid was low (23 micromol/l). Uric acid was, on the other hand, remarkably high (151 micromol/l) compared with that in mammals (cattle, 16 micromol/l). Principally the same results were obtained in chicken and turkey. CONCLUSIONS: Uric acid is a significant UV-absorbing substance in the aqueous humor of diurnal birds with its peak absorbance at 292 nm. The hypothesis that the aqueous humor acts as a UV filter seems to be valid also for the avian eye. However, in these eyes uric acid fulfills the role that ascorbic acid does in mammals.

Absorption↗

[Value of the immunoenzyme method (ELISA) in determining serum and aqueous humor antiherpes immunoglobulin levels (apropos of 155 cases)].

Immuno-enzymatic assay of aqueous humor and serum antiherpetic antibodies was performed in 155 patients with all types of uveitis and with keratitis. Globulin levels were also determined in the two fluids, employing an original nephelometry-laser technique. This immuno-enzymatic technique, which possesses greater reliability, reproducibility, and sensitivity than passive hemagglutination, appears suitable for microassay in aqueous humor, and demonstrates the production of anti-herpes antibodies in this fluid to the exclusion of other specificity. Applying limits of at least 1/40e for H.A. antibody levels, and at least 10 for the immunity load coefficient, these antibodies could be demonstrated in half of the cases of clinically confirmed herpes, in one-third of clinically suspected cases, and in two intermediary cases of uveitis where no predictive signs of herpes were present. In contrast, specific antibodies were never detected in 70 cases of anterior or total uveitis. Measuring anti-herpes antibodies in aqueous humor and serum by the ELISA method, in association with immunity load coefficients determination in the two fluides, appears to be a very useful method for the future etiological diagnosis of anterior and intermediary uveitis when the etiology is uncertain but clinical signs suggest a possible herpetic origin.

Adolescent↗

Aqueous humor flow in normal human eyes treated with brimonidine and dorzolamide, alone and in combination.

OBJECTIVES: To measure the effectiveness of topical 0.2% brimonidine tartrate as a suppressor of aqueous humor flow in the human eye compared with the effectiveness of 2% dorzolamide hydrochloride, and to measure the additivity of the effects of the 2 drugs. DESIGN: A randomized, double-masked, placebo-controlled study was performed in 20 healthy human subjects. The topical drugs were instilled twice daily the day before and again in the morning on the day of the measurements. The rate of aqueous humor flow was measured from 8 AM to 4 PM by clearance of topically applied fluorescein using a fluorophotometer, after administration of doses of each drug singly and both drugs together. Intraocular pressure (IOP) was measured with applanation tonometry. RESULTS: Compared with placebo, brimonidine reduced the aqueous humor flow by a mean +/- SD of 28.2% +/- 18.0% (P<.001), dorzolamide by 19.3% +/- 22.0% (P =.007), and the combination of brimonidine and dorzolamide by 37.2% +/- 20.6% (P<.001). The combination of both drugs statistically significantly suppressed aqueous humor flow compared with dorzolamide alone (P<.001) and brimonidine alone (P =.04). The IOP was reduced by a mean +/- SD of 11.6% +/- 10.1% (P<.001) by brimonidine, 8.5% +/- 14.1% (P =.02) by dorzolamide, and 17.9% +/- 16.5% (P<.001) by the combination. The combination of drugs reduced IOP better than dorzolamide (P<.001), but not more than brimonidine (P =.06). CONCLUSIONS: The combination of brimonidine and dorzolamide caused a further reduction of aqueous humor flow compared with each drug applied alone. The IOP was further reduced by the combination compared with dorzolamide alone, but not compared with brimonidine alone.

Administration, Topical↗