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Increased aqueous humor basic fibroblast growth factor and hyaluronan levels in relation to the exfoliation syndrome and exfoliative glaucoma.

PURPOSE: To quantify the concentrations of basic fibroblast growth factor (bFGF) and hyaluronan (HA) in the aqueous humor of patients with the exfoliation syndrome (XFS) or exfoliative glaucoma (XFG). METHODS: Aqueous humor bFGF and HA levels were measured in 13 patients with XFS and in 7 patients with XFG. The results were compared with those obtained from 17 healthy controls. RESULTS: Mean bFGF levels were significantly higher in the XFG patients than those in the XFS patients, which in turn were higher than the bFGF levels in the healthy individuals. Aqueous humor HA levels in both patients with the XFS and the XFG were significantly higher compared to the controls. CONCLUSION: We suggest that bFGF plays an important role in the pathogenesis of XFS and XFG, as well as in the synthesis of secreted HA, which may result in connective tissue degradation that affects the ocular anterior segment.

Aged↗

Penetration of oral and topical ciprofloxacin into human aqueous humor.

PURPOSE: This study was planned to investigate the penetration of ciprofloxacin into aqueous humor following oral and topical application as a prophylactic antimicrobial agent. METHODS: Forty-six patients undergoing cataract surgery were randomly divided into two groups. In the first group, the patients received 500 mg oral ciprofloxacin eight hours before surgery and in the second, 5 drops of 0.3% ciprofloxacin were applied to the patients every twenty minutes, starting 100 minutes before the surgery. By paracentesis, aqueous samples were taken just before the operation so the interval between the first topical application and paracentesis was 100 minutes. RESULTS: The mean concentration of ciprofloxacin in aqueous humor was 0.63+/-0.29 microg/ml in the first group. The concentration was 0.69+/-0.30 microg/ml in the second group. Both of these mean concentrations were higher than the levels of MIC90 of S.aureus , S. epidermidis, P. aeruginosa and Gram (-) bacteriae. CONCLUSION: As a result, both topically and orally applied ciprofloxacin achieved a significant aqueous concentration. Each route studied might be suitable for surgical prophylaxis or treatment of infections.

Administration, Oral↗

Pharmacokinetics of amikacin and chloramphenicol in the aqueous humor of rabbits.

Composite data describing ocular pharmacokinetics are unreliable because of intersubject variation. To address this problem, an animal model was developed in which multiple aqueous samples from single subjects were obtained. Following direct anterior chamber or intravenous administration of amikacin or chloramphenicol, pharmacokinetic analysis of drug concentrations in the serum and anterior chamber was performed by using a nonlinear least-squares regression program. The number of anterior chamber paracenteses performed did not alter the beta elimination rates or percent penetration into the anterior chamber. The aqueous humor and peripheral-compartment terminal slopes were identical. These data indicate that complete ocular concentration-time curves can be obtained without altering antibiotic pharmacokinetics. Following direct injection into the anterior chamber, the elimination rates for both antibiotics followed a one-compartment model, whereas those following intravenous administration best fit an open, first-order, two-compartment model. Following intravenous administration, the anterior chamber elimination rate constants for both drugs were equal to that of the serum and significantly longer than that following direct injection. The elimination rates of both drugs following direct injection were similar. Systemic administration resulted in drug levels in aqueous humor that persisted longer than those following direct injection. Chloramphenicol, a lipophilic compound, gave higher mean concentrations in aqueous humor than did amikacin. Our model provides a new approach which rigorously examines ocular pharmacokinetics and provides data which suggest that for selected compounds the parenteral route of administration is preferable.

Amikacin↗

[Aqueous humor penetration of topically applied ofloxacin, ciprofloxacin and tobramycin].

OBJECTIVE: To compare the aqueous humor penetration of topically applied ofloxacin, ciprofloxacin and tobramycin in human eyes. METHODS: Senile cataract patients (125 eyes in 125 cases) receiving phacoemulsification were randomized into three groups: ofloxacin, 42 eyes; ciprofloxacin, 41 eyes and tobramycin, 41 eyes. Each group was randomized into five sub-groups, with 8 or 9 eyes in each sub-group. Each group received either 0.3% ofloxacin, ciprofloxacin or tobramycin topical drops preoperatively. Eyedrops were instilled one drop every 15 minutes for six times. Aqueous samples were obtained from different sub-groups during surgery, 7.5, 15.0, 30.0, 60.0 and 120.0 min after the last drop, respectively. Concentration of the antimicrobial agents was determined by the HPLC (high pressure liquid chromatography). RESULTS: Aqueous humor concentration of ofloxacin was significantly higher than that of ciprofloxacin at the same period after the last drop. The bioavailability of ofloxacin was 6 times that of ciprofloxacin. Tobramycin could not be detected by HPLC, so its concentration was lower than the minimum detectable level by HPLC (0.05 micro g/ml). CONCLUSION: Ofloxacin has the best aqueous penetration in human eyes, as compared with ciprofloxacin and tobramycin, which suggests ofloxacin could be the preferred topical medicine for the prevention and treatment of endophthalmitis.

Administration, Topical↗

Low content of the natural ocular anti-angiogenic agent pigment epithelium-derived factor (PEDF) in aqueous humor predicts progression of diabetic retinopathy.

AIMS/HYPOTHESIS: Retinopathy is the most common microvascular complication of diabetes. Our aim was to address the predictive value of pro-angiogenic and anti-angiogenic markers for progression of retinopathy. METHODS: Aqueous humor was collected at cataract surgery from 32 diabetic patients who had no or very mild retinopathy (ETDRS stage </=20) and 33 normoglycaemic control subjects. Content of pro-angiogenic vascular endothelial growth factor and angiogenic inhibitor pigment epithelium-derived factor were determined. ANGIOGENIC activity was quantified by measuring its effect on the migration of capillary endothelial cells. The predictive value of the initial level of these markers for progression of retinopathy was studied by following the probands for a maximum of 75 months. RESULTS: In the aqueous fluid content of vascular endothelial growth factor was increased in diabetic patients (mean values 492 versus 292 pg/ml; p=0.0052), and pigment epithelium-derived factor values were decreased (mean values 1740 versus 3680 ng/ml; p=0.0058) compared to control subjects. Of the diabetic patients ten progressed during follow-up (ETDRS stage >47B). This subgroup showed lower pigment epithelium-derived factor content when compared to non-progressors and control subjects. Migratory activity in samples of patients from the control group and in diabetic patients without progression was generally inhibitory due to pigment epithelium-derived factor. Inhibition was blocked by neutralizing antibodies to pigment epithelium-derived factor. In diabetic patients initial angiogenic activity was higher in those who later developed retinopathy (vs. controls p=0.00005; vs. no progressors p=0.0003). Both pigment epithelium-derived factor and migratory response predicted progression. CONCLUSION/INTERPRETATION: Pigment epithelium-derived factor is an important negative regulator of angiogenic activity of aqueous humor. Its content in the aqueous humor of diabetic patients strongly predicts who among them will develop progression of retinopathy.

Aged↗

Intraoperative bacterial contamination of the aqueous humor.

Indigenous ocular flora has been presumed to be a source of infectious organisms in postoperative bacterial endophthalmitis. While bacteria have been recovered from the anterior chamber at the time of cataract wound closure in a significant percentage of cases, and bacteria from the vitreous of endophthalmitis cases have appeared genetically to be very similar to bacteria recovered from the adnexa and/or nares at the time of vitrectomy for endophthalmitis, no study has examined the relationship between organisms isolated from the eyelid and conjunctiva, and organisms recovered from the aqueous humor at the time of wound closure. This study examined 59 eyes undergoing cataract and other intraocular surgeries. Cultures of the eyelids and conjunctiva were taken before and after routine preparation with povidone-iodine solution. Cultures also were taken of the aqueous humor at the time of incision into the anterior chamber and at the time of wound closure. No organisms grew from aqueous humor samples taken at the time of incision. However, 13 eyes (22%) grew gram-positive organisms from samples taken at the time of wound closure. Eight of the 13 eyes (62%) had organisms with identical typing and antibiotic sensitivities to organisms isolated from the eyelids and conjunctiva before or after disinfection. This study suggests that a significant number of cases had inoperative bacterial contamination of the aqueous humor by the time of wound closure and that organisms from the eyelids and conjunctiva are an important source of contamination in these cases.

Anterior Eye Segment↗

[Fluorophotometry by instillation. I. Flow of the aqueous humor and corneal endothelial permeability].

Among various fluorophotometric methods performed on the anterior segment, topical administration of fluorescein was developed. This local administration allows to measure the aqueous humor flow and the permeability of the corneal endothelial. The examinations are performed on a computerized fluorophotometer: the Fluorotron Master. This fluorophotometer has been designed to accurately measure fluorescein's concentrations into the eye and especially in aqueous humor and cornea. Anterior chamber adapter magnifies the scan for detailed work in the anterior chamber and lens. The Fluorotron is supplied with a cuvette holder and a cuvette which is adapted to the optical head for measuring the concentration of fluorescein in blood plasma or in buffered aqueous samples. A good linearity was obtained between the meter readings and the concentrations of fluorescein in phosphate buffer with pH 7.4, within the range between 1 ng and 1000 ng. Based upon the mathematical analysis of Yablonski the method by fluorescein instillation is simple and safe and gives the loss coefficient, ko, of the dye from the anterior chamber, the aqueous humor flow, F, and the endothelial transfer coefficient kc.ca. Calculations were carried out on twenty one normal eyes yielding average values for F 2.97 +/- 0.93 microliter.min-1 (Mean +/- S.D.) and for kc.ca 4.02 +/- 0.40. 10(-1) min-1. These values are comparable to those of other authors.

Aqueous Humor↗

Significant variation of the elevated nitric oxide levels in aqueous humor from patients with different types of glaucoma.

Though several studies have shown that the biochemical function of nitric oxide (NO) in the eye might play an important role in the regulation of intraocular pressure (IOP), local control of ocular blood flow and loss of retinal ganglion cells by apoptosis, it is unclear whether the role of NO is similar in the pathogenesis of different kinds of glaucoma: primary open-angle glaucoma (POAG), chronic closed-angle glaucoma (CCAG) and neovascular glaucoma (NVG). To further explore this issue, we measured the concentrations of NO in aqueous humor and plasma samples from patients with POAG (n = 31), CCAG (n = 76), NVG (n = 8) and cataract (n = 30). All of the NVG patients suffered from severe proliferative diabetic retinopathy, while other patients were free of any other systemic disease. The NO levels in both aqueous humor and plasma samples were assessed by chemiluminescence assay. We found that the NO levels in aqueous humor samples were greatly varied in patients with POAG (36.2 +/- 3.3 microM), CCAG (47.7 +/- 3.4 microM) and NVG (65.8 +/- 5.4 microM), and all of them were significantly higher than in cataract patients (27.0 +/- 2.9 microM p < 0.05). Except NVG patients whose NO levels in plasma samples were highest (24.1 +/- 3.5 microM) among all groups, the plasma NO levels were not significantly different between the other glaucoma patients and the cataract patients. We therefore concluded that significant variation of the elevated NO levels in aqueous humor samples from the patients with different types of glaucoma may reflect their differences in the pathogenesis.

Aged↗

The effect of topical CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure and aqueous humor dynamics in rabbits.

PURPOSE: To evaluate the ocular hypotensive effect of topical CS-088, an angiotensin AT1 receptor antagonist, and the effect of CS-088 on aqueous humor dynamics. METHODS: The effects of CS-088 on intraocular pressure (IOP) were studied in 2 models of rabbit ocular hypertension. Experimental ocular hypertension was induced in albino rabbits by injecting alpha-chymotrypsin into the anterior chamber (alpha-chymotrypsin rabbit). The effects of the single application of CS-088 were examined. Additionally, CS-088 was repeatedly administered over a period of 3 weeks to hereditary ocular hypertensive rabbits (buphthalmic rabbits, JWHR bu/bu) and the IOPs were monitored throughout the experiment. The effects of CS-088 on aqueous humor dynamics were also examined in normal rabbits. In this study, the methods of IOP recovery rate, two-level constant pressure perfusion and fluorescein-dextran perfusion were used respectively to determine the aqueous inflow, outflow facility and uveoscleral outflow (USF). RESULTS: CS-088 at 1% and 2% significantly lowered the IOP in the alpha-chymotrypsin rabbits with a maximum IOP reduction of 10.1 mmHg. The maximum effect obtained with 2% CS-088 was no greater than that with 1% CS-088. In the buphthalmic rabbits, 2% CS-088 also lowered IOP significantly. Timolol was effective in both models. In the study on aqueous humor dynamics, a slight increase in USF (17%) was seen after a topical application of CS-088 whereas changes in aqueous inflow or outflow facility were not observed. CONCLUSIONS: Topical CS-088 can decrease IOP in rabbits. Despite the USF change, the ocular hypotensive mechanism by CS-088 was not fully determined.

Administration, Topical↗

[Aqueous humor and serum interleukin-6 in patients with uveitis].

PURPOSE: A study on local and systemic behavior of interleukin-6 in patients with active uveitis. METHODS: IL-6 levels were measured in aqueous humor and peripheral blood samples using an enzyme-linked immunosorbent assay (ELISA) from 23 patients with uveitis and 16 control patients who had been operated for uncomplicated cataracts. RESULTS: Aqueous humor of patients with uveitis showed higher levels of interleukin-6 than those of controls (p<0.001). A comparison of cytokine levels between aqueous humor and serum from patients with uveitis showed significantly higher levels of interleukin-6 in aqueous than serum (p<0.001). Correlation studies using regression test for successive steps failed to demonstrate any association between interleukin-6 levels and the different clinical characteristics of uveitis patients (laterality, onset, patterns, visual damage, localization, inflammatory activity, etiology, and association with the B27 + histocompatibility antigen). CONCLUSIONS: IL-6 is a cytokine that actively participates in the pathogenesis of clinical uveitis. Our data emphasize the greater local than systemic participation of this cytokine.

Adolescent↗

Aqueous humor factors and their effect on the immune response in the anterior chamber.

The immune response to antigens within the anterior chamber is deviant (anterior chamber associated immune deviation - ACAID) in that delayed hypersensitivity is deficient, whereas other immune effector modalities are intact. Experimental evidence indicates that the eye itself is critical to the induction of ACAID. We have examined the antigen processing and presenting potential of cells within the anterior segment of the eye, and have analyzed the potential immunoregulatory properties of these cells, their secretory products, and the aqueous humor itself. Evidence indicates that bone marrow-derived cells within the stroma of the iris and ciliary body inhibit antigen-driven T lymphocyte activation, although they themselves lack the capacity to present antigens to T lymphocytes. The mechanism is in part through secretion of immunosuppressive cytokines. Since aqueous humor contains similar cytokines, it is inferred that these molecules are constitutively secreted. We have determined that a major inhibitory molecule within normal aqueous humor is transforming growth factor-beta (TGFB), which inhibits antigen processing and presentation, and suppresses both T lymphocyte activation and certain aspects of non-specific inflammation. These effects also turn out to be properties of normal aqueous humor. These findings support the hypothesis that local features of the eye modify intraocular antigens such that an ACAID-inducing signal is produced. Experimental evidence suggests that these same properties may play a major role in suppressing efferent immune responses in the eye.

Animals↗

Detection of uric acid in aqueous humor by high pressure liquid chromatography.

The uric acid peak among the compounds in aqueous humor separated by high pressure liquid chromatography was identified by its retention time, the UV absorbance characteristics, and the effect of uricase. The uric acid concentration in the aqueous humor of normal monkey, human eyes with cataract, and human eyes with glaucoma are less than 0.05, 1.7 +/- 0.3, and 3.8 +/- 0.4 respectively. The significance of high uric acid concentration in glaucoma is discussed.

Animals↗

Fluorescein angiography and changes in aqueous humor protein after argon laser photomydriasis in rabbits.

In brown-eyed and blue-eyed rabbits, irises treated with argon laser photomydriasis (ALP) were studied by using fluorescein angiography and by evaluating the aqueous humor protein concentration. The following results were obtained. Immediately after ALP, a breakdown of the blood-aqueous barrier is demonstrated by a marked influx of fluorescein into the ciliary processes and into the anterior and posterior chambers. The dye flow into the aqueous humor decreases to normal values within 3 days. There is no fluorescein leakage from laser impacts themselves. Peripupillary capillary loops are permanently occluded, but in a few cases, recanalization occurs. Neovascularization did not occur during 56 days of observation. ALP initially leads to a six- to eightfold increase in normal aqueous humor protein concentration, which decays to normal values within 3 days.

Animals↗

Immunoglobulin E in human aqueous humor and corresponding serum. A physiopathological and clinical study.

The analysis of IgE in aqueous humor yielded an average concentration of 3.4 +/- 0.97 U/ml for 22 cataract patients and 5.5 +/- 3.42 U/ml for five uveitis patients. The IgE level in aqueous humor (IgEa.h.) of the cases examined is most probably, beside hematoocular diffusion of serum IgEs, the result of intra-ocular IgE production. In comparison with (mostly normal) IgEs levels, the IgEa.h. concentration appears relatively elevated, not only with uveitis patients, but also with cataract patients, above all when lenticular opacity is accompanied by other ophthalmic diseases (glaucoma, high myopia, diabetes). This "increase" of IgEa.h. concentration in very probably due to the radioimmunosorbent (RIST) technique employed, the most sensitive method available at the time of the present study. Thus, the calculated IgEa.h. value in the cataractous eyes should be regarded simply as approximate to the normal IgEa.h. concentration. These values are of clinical significance however, since a reference IgEa.h. mean-value is indispensable to the interpretation of pathologically high IgEa.h. levels and ethics do not permit of IgEa.h. determination in healthy eyes. The mean IgEa.h. levels of the delayed-type uveitis and cataract patients examined reveal no significant differences. IgEa.h. determination could make a contribution to the etiological clarification of, for example, immediate-type uveitis cases and intra-ocular parasitosis and serve as an appropriate model to study intra-ocular immunomechanisms.

Adult↗

Nitric oxide levels in aqueous humor after lens extraction and poly(methyl methacrylate) and foldable acrylic intraocular lens implantation in rabbit eyes.

PURPOSE: To measure the nitric oxide (NO) level in the aqueous humor of rabbit eyes after common cataract surgery techniques. SETTING: Department of Ophthalmology, Military Medical University, and Department of Immunology and Immunotoxicology of Respiratory System, Clinic of Pneumonology and Allergology, Medical University of Łódź, Łódź, Poland. METHODS: Thirty rabbits were randomly divided into 4 groups, and surgery was performed as follows: Group 1, extracapsular cataract extraction (ECCE) and poly(methyl methacrylate) (PMMA) intraocular lens (IOL) implantation; Group 2, ECCE; Group 3, phacoemulsification and foldable acrylic IOL implantation; Group 4, phacoemulsification. The aqueous humor specimens were collected on days 1, 3, and 5. Nitric oxide measurements were performed indirectly with a spectrophotometer. The NO level in the aqueous humor collected before surgery served as a control group. RESULTS: In the physiological condition, the concentration of NO was 26.52 nm/dL +/- 4.86 (SD). Postoperatively, the highest NO level in each groups was as follows: Group 1, 46.26 +/- 5.23 nm/dL on day 3; Group 2, 72.46 +/- 6.94 nm/dL on day 1; Group 3, 41.04 +/- 7.31 nm/dL on day 1; and Group 4, 32.67 +/- 2.84 nm/dL on day 3. Significantly higher levels of NO (P <.05) were observed in Groups 1 and 2 at each follow-up day; in Group 3, on days 1 and 3; and in Group 4, on day 3. CONCLUSIONS: Techniques of cataract extraction caused the NO level to increase; however, phacoemulsification with a foldable IOL caused the smallest release of NO. Rapid postoperative NO changes may theoretically contribute to blood-aqueous barrier breakdown secondary to cataract surgery.

Acrylic Resins↗

[An experimental study of cytology in the aqueous humor of rabbit eyes after intraocular lens implantation].

OBJECTIVE: The study was designed to count the number of white blood cells and observe their subset distribution in the aqueous humor after extracapsular lens extraction and intraocular lens (IOL) implantation in capsular bag in rabbits and to discuss the mechanism of postoperative intraocular inflammatory response. METHODS: 27 adult pigmented rabbits were divided into three groups: (1) The IOL was placed in the capsular bag after extracapsular lens extraction; (2) The extracapsular lens extraction; and (3) The control group without any surgical intervention. Aqueous humor samples were aspirated on the postoperative 1, 3, 7 and 14 days, and the total number of white blood cells in the aqueous humor and their subset distribution were counted. The data were analyzed by using analysis of variance of SAS software. RESULTS: There was a significantly higher number of inflammatory cells in the IOL implanted eyes than that in the eyes with only extracapsular lens extraction. CONCLUSIONS: In the early postoperative stage, there was a marked increase in the number of white blood cells and polymorphonuclear leukocytes in the IOL group, that is probably related to the mechanical ocular tissue damage and the breakdown of the blood-aqueous barrier induced by the operative procedures. There were a significant increase in the macrophages, eosinophiles, and lymphocytes in the IOL group, that suggests that an active immune response exist in the anterior ocular inflammation after IOL implantation.

Animals↗

Elevated prolactin levels in human aqueous humor of patients with anterior uveitis.

Evidence is accumulating that prolactin (PRL) may play a physiological role in the regulation of humoral and cell-mediated immune responses. On the basis of these observations, we measured levels in the serum and aqueous humor of 28 patients with cataract or anterior uveitis with concomitant cataract. Intraocular concentrations were measured in a range from 0.1 to 3.4 ng/ml. Whereas serum PRL levels failed to show significant differences between the two groups (P = 0.39), intraocular concentrations were significantly higher in uveitis patients (P less than 0.001). The level in aqueous humor did not reflect the serum concentration in either group. To the best of our knowledge, this is the first study measuring PRL concentrations in human aqueous humor.

Adolescent↗

Effects of cyclocryotherapy on aqueous humor dynamics in cats.

The effects of graded cyclocryotherapy were studied using pneumatonometry, fluorophotometry, and light and electron microscopy. Cats were treated with either 90 degrees, 180 degrees, or 270 degrees of cyclocryotherapy and were followed up for six weeks. The response of the eyes to treatment was evaluated in terms of intraocular pressure (IOP) response, aqueous humor flow rate, and permeability of the blood-aqueous barrier compared with the untreated fellow eye. The average IOP response was determined to be -20%, -44%, and -47% for the 90 degrees, 180 degrees, and 270 degrees treated eyes, respectively. The aqueous humor flow rate was estimated to be -14%, -44%, and -52% for each of the groups, respectively. Finally, the permeability of the blood-aqueous barrier, measured 60 minutes after injection of fluorescein, was estimated to be a percent increase of 22%, 332%, and 285% for each of the groups, respectively. Histologically, the maximally treated eyes (270 degrees) demonstrated greater disruption of the ciliary body compared with the control eyes. Thus, graded cyclocryotherapy causes graded destruction of the ciliary epithelium and proportionally related changes in IOP and aqueous humor dynamics.

Animals↗