[Unusual case; eyelashes in the aqueous humor].
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We evaluated T-lymphocyte subsets in 18 patients with active untreated uveitis and in 20 controls by monoclonal OKT (Ortho-Kung-T cell) antibodies. Both OKT4- and OKT8-positive cells were detected in the aqueous humor of patients with uveitis. The percentage of OKT4-positive cells (21.1 +/- 7.4) was larger than that of OKT8-positive cells (15.2 +/- 5.3) and the OKT4-OKT8 ratio was 1.40 +/- 0.3. A comparison of aqueous humor and peripheral blood cells from patients with uveitis showed diminished frequencies of OKT4- and OKT8-positive cells. The OKT4-OKT8 ratios were not significantly different. A comparison of peripheral blood cells from patients with uveitis and from controls showed that patients with uveitis had lower OKT4-OKT8 ratios. Lower percentages of OKT4-positive cells were also observed in the peripheral blood cells of patients with uveitis.
BACKGROUND AND OBJECTIVE: Investigation of the penetration of topical ciprofloxacin into aqueous humor. PATIENTS AND METHODS: Topical 0.3% ciprofloxacin drops were administered to 17 patients with cataracts before lens extraction surgery. The time interval between the first dose and sampling was 3 hours in 9 patients (group A) and 6 hours in 8 (group B). In both groups, aqueous samples were collected 30 minutes after the last ciprofloxacin application. Ciprofloxacin concentration was determined by high-performance liquid chromatography-fluorescence detection. RESULTS: Mean aqueous concentration was 0.83+/-0.48 microgram/ml in group A and 2.42+/-1.42 micrograms/ml in group B. CONCLUSION: Topical 0.3% ciprofloxacin penetrates into the aqueous in a significant concentration.
The transforming growth factor-beta s are peptide growth factors known to play a central role in wound healing. Using a specific, in vitro assay of cell growth inhibition, we have detected transforming growth factor-beta (TGF-beta) in 24/24 aqueous humor specimens from eyes undergoing cataract extraction with intraocular lens implantation. The amount of TGF-beta ranged from 2.3 to 8.1 ng/ml (mean +/- SD = 4.5 +/- 1.7 ng/ml), with 61% present in the active form. Subtyping of TGF-beta was performed by addition of antibodies specific for the beta 1 and beta 2 isoforms to the growth inhibition assay, and confirmed with a sandwich enzyme-linked immunosorbent assay. None of the TGF-beta detected was of the beta 1 isoform; in contrast, the beta 2 isoform was present in every sample, implying that it might have originated from ocular tissues. The presence of this potent modulator of tissue repair in aqueous humor suggests a role in the healing processes following intraocular surgery, including glaucoma filtration surgery.
Prednisolone, prednisolone acetate and prednisolone sodium phosphate are glucocorticoids used for ocular, anti-inflammatory therapy. A reversed-phase high-performance liquid chromatographic assay using ultraviolet detection has been developed that affords baseline resolution of the above analytes in balanced salt solutions and rabbit aqueous humor. The drugs can be quantified at 0.025-0.05 micrograms/ml in the above matrices; 6 alpha-methylprednisolone is used as the internal standard. Both esters of prednisolone are vulnerable to chemical and enzymatic hydrolysis giving prednisolone. Analysis of aqueous humor samples shows prednisolone acetate penetrating/metabolizing primarily to prednisolone; prednisolone sodium phosphate penetrates the cornea giving the ester and alcohol.
We studied the serologic findings in serum and aqueous humor samples from 693 cases of uveitis. Specimens were tested for the presence of humoral antibodies against tuberculosis, toxoplasmosis, antistreptolysin-O, herpes simplex and herpes zoster viruses, mumps virus, and adenovirus. Serologic analyses rarely indicated tuberculous or streptococcal infections, but frequently showed toxoplasmosis and viral diseases.
BACKGROUND: Tissue factor (TF) is a cellular initiator of the coagulation cascade and is upregulated by the major factors of diabetic angiopathy, TF might thus be one of the key molecules in diabetic retinopathy (DR). PURPOSE: To measure TF in diabetic eyes and evaluate its possible role in DR. METHODS: TF concentration in the aqueous humor of the eyes in 44 patients with diabetes and 35 age-matched control patients was evaluated by ELISA. The concentration of TF in aqueous humor (AH) was compared with the grade of DR. The concentration of TF in AH was also compared with duration of diabetes, renal function, and blood glucose control. The serum TF concentration in each group was also compared. The correlation between the serum TF and aqueous TF in each patient was analyzed. The effect of vascular endothelial growth factor (VEGF) on the TF activity of cultured bovine retinal endothelial cells was evaluated. RESULTS: The mean TF concentration in AH was higher in patients with active proliferative DR (244.5 pg/ml) than in either those with non-proliferative DR (132.4 pg/ml, P<0.05) or the control patients (114.9 pg/ml, P<0.01). The serum TF concentration in active proliferative DR patients (348.3 pg/ml) was significantly higher than in either non-proliferative DR patients, (235.9 pg/ml, P<0.01) or in the controls (223.5 pg/ml, P<0.01). However, the TF concentration of AH was not significantly correlated to that of the serum in each patient. The TF concentration in AH closely correlated with the grade of DR and protein concentration. VEGF increased the biological activity of TF in vitro. CONCLUSION: The origin of TF in AH, however, is still not clearly understood. Nonetheless, TF in AH directly reflects the severity of ocular diabetic change, and the present results indicate that TF indeed plays some role in the progression of DR.
The pharmacokinetic properties of indomethacin and its effects on aqueous protein values were studied in 15 clinically normal Beagles. The dogs were treated every 6 hours with 1% indomethacin suspension in 1 eye, with the other eye serving as a control. After 24 hours, the dogs were anesthetized and samples of aqueous humor (AH) were drawn by aqueocentesis at 0, 15, 30, 60, and 90 minutes after initial paracentesis. Additional samples were drawn at the time of euthanasia, 180 (6 dogs) and 360 minutes (9 dogs) minutes after initial paracentesis. Blood samples were obtained at each treatment and at each aqueocentesis. The eyes were enucleated after dogs were euthanatized. Aqueous protein concentrations and indomethacin concentrations in AH, plasma, and different ocular tissues were determined. Topical indomethacin administration had no effect on baseline protein concentrations of AH. It reduced protein concentrations in AH significantly at all times after initial aqueocentesis. This reduction was approximately 30%. Indomethacin in the AH is mostly protein-bound. Concentrations were 350 ng/ml in primary AH and 1,305 ng/ml in secondary AH, 90 minutes after initial aqueocentesis. Free-drug concentrations were relatively constant at about 220 ng/ml. Indomethacin administered topically is readily absorbed by the ocular adnexae, reaching a steady-state concentration of 25 ng/ml in blood plasma 18 hours after the start of treatment. Plasma concentrations were 50 times lower than therapeutically effective concentrations. High indomethacin concentrations were found in the cornea only. Low concentrations were found in the iris and ciliary body, the lens, and in the choroid.(ABSTRACT TRUNCATED AT 250 WORDS)
A posterior route for the drainage of aqueous humor was determined, using latex spheres as tracers. Continuous intracameral injections were made on live Beagles for periods up to 1 hour. Intraocular pressure was maintained between 15 and 30 mm of Hg during the infusion process. Tissue macrophages ingested many of the spheres, and their ingestion served to fix the position of the markers as they passively followed aqueous drainage routes. Thin sections were prepared from tissues that reportedly constituted the uveoscleral route. The electron microscope was used to visualize the latex spheres within the macrophages. In this manner, a uveoscleral pathway was demonstrated in normal Beagles.
It has been suggested that the trabecular meshwork may be involved in the pathogenesis of open-angle glaucoma, and some authors have pointed out that disorders of the extracellular matrix components may play a role; nevertheless, nothing is known about the normal metabolism of connective tissue molecules in this particular tissue. We recently initiated some studies in this field and have focused on the in vitro effects of aqueous humor on collagen metabolism. We report the finding of a latent collagenase of low molecular weight in aqueous humor obtained from cataractous patients; the enzyme was identified through several methods, including its in vitro activity against radiolabelled type I collagen and additionally with a zymogram technique. It was partially characterized by high-performance liquid chromatography.
For immunocompetent patients, ocular toxoplasmosis is the most frequent infectious cause of chorioretinal inflammation. Nowadays, the laboratory diagnosis of ocular toxoplasmosis requires serological tests and anterior chamber puncture to detect the local production of specific antibodies. The authors describe a new technique to detect toxoplasma in aqueous humor by a polymerase chain reaction in which the target is a 88 bp specific rDNA fragment. 31 patients were concerned (23 highly suspect of ocular toxoplasmosis and 8 controls). The presence of the parasite in aqueous humor was found in 7 cases. No false positive was detected. The sensitivity of the test is reduced by the poor volume of the sample. The combination of this technique with Desmont's coefficient gives a better positive predictive value. We emphasize the pathophysiological value of this technique by suggesting the presence of tachizoites in the anterior chamber. According to our knowledge, this finding has never been demonstrated. In the future, this should be a very promising technique for the diagnosis of ocular toxoplasmosis.
Topical administration of nylidrin hydrochloride lowered intraocular pressure in both albino rabbits and cynomologus monkeys. The maximum decrease occurred two hours following drug application and was unilateral. The response lasted four hours in monkeys and at least six hours in rabbits. Outflow facility, episcleral venous pressure, and aqueous humor flow measured by fluorophotometry were unaltered in both species. In rabbits in the treated eyes, ocular blood flow was increased, and anterior and posterior chamber ascorbate concentrations were unchanged. The mechanism of IOP reduction appears to be increased aqueous humor outflow via uveoscleral outflow routes that are not pressure dependent.
We treated seven patients (all male, ranging in age from 11 to 31 years) with Schwartz syndrome, a combination of uveitis, high intraocular pressure, and retinal detachment with peripheral tears. The condition was resistant to corticosteroids but responded well to surgery. Puncture of the anterior chamber disclosed many outer segments of the visual cells with few inflammatory cells in the aqueous humor in all seven patients. Possibly the outer segments, flowing from the subretinal space through the peripheral retinal break into the aqueous humor, cover the trabecular meshwork and cause the decrease in the coefficient of outflow. Detection of the outer segments led us to make a definite diagnosis and institute the appropriate treatment.
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The majority of ocular infections in the industrialized countries arise after surgical interventions. An appropriate antibacterial prophylaxis is therefore highly desirable in eye surgery. We used high performance liquid chromatography (HPLC) to measure the concentrations reached by imipenem, a modern wide-spectrum beta-lactam antibiotic, in plasma and aqueous humor of 26 patients scheduled for cataract surgery. Even a single 500 mg dose of imipenem achieved therapeutic levels of the molecule for the most common ophthalmic pathogens (1 microgram/ml or above) in the aqueous humor within one to two hours after administration. This drug may therefore be suitable for antibacterial prophylaxis in eye surgery.
PURPOSE: PhXA41, a new phenyl-substituted analog of a prostaglandin F2 alpha (PGF2 alpha) prodrug (13,14-dihydro-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-1-isopropyl ester), is an effective ocular hypotensive agent in patients with glaucoma. To understand its mechanism of action, various components of aqueous humor dynamics were examined after topical application to human eyes. METHODS: In a randomized, double-masked, placebo-controlled study, PhXA41 (0.006%) was given topically twice daily for 1 week to one eye each of 22 volunteers with normotension or ocular hypertension. The other eye was similarly treated with vehicle. Intraocular pressure (IOP) was measured by pneumatonometry and tonographic outflow facility by pneumatonography. Aqueous flow and outflow facility were determined either directly or indirectly by a fluorophotometric technique, and uveoscleral outflow was calculated secondarily. Comparison of values obtained in treated versus contralateral control eyes and on baseline versus day 8 of treatment were made. RESULTS: Compared with baseline measurements, PhXA41 significantly (P < 0.001) reduced IOP by 5.5 +/- 0.6 mmHg (mean +/- standard error of the mean) as measured 3 hours after the last dose on the eighth day of treatment. Aqueous flow, tonographic outflow facility, and fluorophotometric outflow facility were not changed by PhXA41. However, uveoscleral outflow was significantly greater in the PhXA41-treated eyes (0.87 +/- 0.22 microliter/minute) compared with either the contralateral vehicle-treated eyes (0.14 +/- 0.30; P < 0.02) or baseline measurements (0.39 +/- 0.20 microliter/minute; P < 0.05). CONCLUSIONS: PhXA41 decreases IOP in humans by increasing uveoscleral outflow without significantly affecting other parameters of aqueous humor dynamics.
Uveitis is a manifestation of various chronic inflammatory arthritic conditions. There are considerable data implicating abnormalities of immune function in the etiopathogenesis of uveitis. We evaluated the percentage of cells expressing interleukin 2 (IL-2) receptor (membrane bound) and the levels of soluble IL-2 in the blood and aqueous humor of patients in various rheumatic diseases and acute untreated uveitis. Our findings showed increased IL-2 receptors (IL-2R) and soluble IL-2 receptors on the aqueous humor of patients with uveitis when compared to healthy controls. These results suggest an immunoregulatory role of IL-2R in acute uveitis and raises the possibility that its detection may be useful in management.
PURPOSE: To monitor changes of endogenous hyaluronan in the iris tissue and aqueous humor after an isolated trauma to the iris by argon laser irradiation of the anterior surface of the iris. METHODS: Iris and aqueous hyaluronan concentrations in rabbit were measured with a radiometric assay at different time points after laser irradiation. RESULTS: Total hyaluronan content in iris tissue increased 3-fold to a peak concentration of 71-72 microg/g at 1 and 2 days after laser treatment. Aqueous hyaluronan increased to a maximum of about 1.6 microg/ml at 2 h and 12 h after laser irradiation of the iris. CONCLUSIONS: The iris tissue responds with increased hyluronan synthesis to an isolated iris argon laser irradiation and it seems to be the most important source of aqueous hyaluronan.