Disruption Of Blood-aqueous Barrier Research Articles

Comparative efficacy of topically applied flurbiprofen, diclofenac, tolmetin, and suprofen for the treatment of experimentally induced blood-aqueous barrier disruption in dogs

Abstract Objective To compare the relative efficacies of 4 topical nonsteroidal anti-inflammatory drugs at preventing blood-aqueous barrier (BAB) disruption in dogs. Design 1 eye of each dog was treated with 1 % suspensions of diclofenac, flurbiprofen, suprofen, or tolmetin, or with control solution. After 4 applications of eyedrops at 10-minute intervals, BAB disruption was induced in the treated eye by anterior chamber paracentesis. The severity of BAB disruption was measured by anterior chamber fluorophotometry. Animals 40 ocular-normal dogs. Procedure After pretreatment with eyedrops, rapid, 100-μl nonleaking anterior chamber paracentesis was performed in 1 eye of each dog to induce BAB disruption. 1 day after paracentesis, 1 ml of 10% fluorescein sodium was injected IV. The amount of fluorescein entering the anterior chamber of each eye was measured 30 to 60 minutes later by use of a computerized scanning fluorophotometer. The degree of BAB disruption was determined by comparing the amount of fluorescein entering the aqueous humor of the paracentesed eye with that of the nonparacentesed eye. Results At postparacentesis day 1, the order of statistically significant BAB-stabilizing efficacy among groups was: diclofenac > flurbiprofen > suprofen > tolmetin = control solution. Conclusions Topically applied 1% suspensions of diclofenac, flurbiprofen, and suprofen are effective at preventing BAB disruption after paracentesis in dogs, indicating their potential usefulness for treatment of prostaglandm-mediated ocular disease. 1 % tolmetin is no more effective than control solution. (Am J Vet Res 1996;57:875–878)

Effect of cataract surgery on aqueous turnover and blood-aqueous barrier

We evaluated changes in aqueous outflow and blood-aqueous barrier (BAB) disruption after cataract surgery in two randomly selected groups of eyes. In one group, a high-viscosity viscoelastic was used for intraocular lens (IOL) implantation; in the other, a low-viscosity viscoelastic. Fluorophotometry was used to evaluate aqueous humor dynamics five to seven hours after IOL implantation. Aqueous outflow after IOL implantation in operated eyes was nearly twice that in the fellow eyes, which served as controls. Mean protein concentration in the anterior chamber was also elevated in operated eyes. However, postoperative aqueous outflow did not differ significantly between the two groups. The substantial increase in aqueous outflow observed postoperatively and the increase in aqueous humor protein concentration were closely related to BAB disruption. These results suggest that BAB disruption may be a main cause of the transient high intraocular pressure observed after IOL implantation in both groups.

Sensitivity of Laser Flare Photometry to Monitor Inflammation in Uveitis of the Posterior Segment

Laser flare photometry is a new quantitative method for evaluating aqueous flare, making flare the only inflammatory parameter that can be evaluated precisely and objectively. The validity of the method already has been demonstrated in anterior segment inflammation. The aim of this study is to assess the validity and limitations of the method to quantify and monitor inflammation in uveitis with predominant involvement of the posterior segment. Five well-defined conditions with uveitis predominant in the posterior segment were analyzed in this study: Behçet uveitis, pars planitis, posterior sarcoidosis, posterior pole toxoplasmosis, and birdshot chorioretinopathy. (1) Mean initial (pretreatment) flare was determined; (2) in the patients needing systemic steroid therapy, introduction of therapy was correlated with evoluting laser flare photometry; and (3) in patients with quiescent disease, the predictive value of a defined subclinical photometry-detected flare rise for disease recrudescence was analyzed. Initial pretreatment flare was 331.8 +/- 47.7 photon counts per millisecond (ph/msecond) (mean +/- standard error of the mean) for Behçet uveitis, 15.6 +/- 1.3 ph/msecond for pars planitis, 26.9 +/- 4.6 ph/msecond for posterior sarcoidosis, 7.5 +/- 1.0 ph/msecond for posterior pole toxoplasmosis, 5.8 +/- 0.7 ph/msecond for birdshot chorioretinopathy, and 4.7 +/- 0.1 ph/msecond for a group of 88 control eyes. A significant flare reduction after start of steroid therapy was seen in Behçet uveitis (78% reduction), sarcoidosis (44.8%), and pars planitis (51%), but not in toxoplasmosis or in birdshot. A small flare rise had a predictive value for disease recrudescence in 27/35 patients (predictive value, 0.77; sensitivity rate, 100%). The level of associated blood-aqueous barrier disruption for reliable follow-up of posterior uveitis was empirically determined to be 13 to 15 ph/msecond. Laser flare photometry was found to be very sensitive to monitor inflammation in uveitis of the posterior segment as long as a sufficient level of associated blood-aqueous barrier disruption (flare) was present.

Apraclonidine Protection of the Blood-Aqueous Barrier from Traumatic Break-Down

This study investigated the effects of apraclonidine hydrochloride 1% eye drops on blood-aqueous barrier in 108 pigmented rabbits. The effects of pretreatment with dapiprazole and yohimbine, and a comparison with clonidine 0.125% eye drops are also reported. The disruption of blood-aqueous barrier was obtained by argon laser burning of the iris. The degree of permeability of the barrier was deduced by the amount of proteins in aqueous humor 60 min after laser application. Intraocular pressure and pupil diameter were also studied. Protein content in aqueous humor was 0.72 +/- 0.26 g/l in control rabbits that did not receive any treatment; 5.98 +/- 4.23 g/l in rabbits instilled with placebo eye drops and treated by laser burning of iris; 0.43 +/- 0.25 g/l in rabbits that received apraclonidine eye drops prior to laser burning; 2.19 +/- 1.3 g/l in rabbits that received apraclonidine eye drops immediately after laser application; 0.35 +/- 0.08 g/l in rabbits that received apraclonidine 1% eye drops both before and after laser application. Rabbits treated with clonidine 0.125% had a protein content in aqueous humor of 5.45 +/- 2.08 g/l after laser application. Dapiprazole 0.5% eye drops prior to apraclonidine led to a protein content in aqueous humor of 1.93 +/- 2.13 g/l; yohimbine 0.3% eye drops prior to apraclonidine led to a protein content of 0.70 +/- 0.40 g/l. Protein content in aqueous humor was 0.93 +/- 0.36 g/l, 0.82 +/- 0.899 g/l and 1.68 +/- 1.39 g/l in rabbits treated with yohimbine 0.3, 0.6 and 1.2 mg/kg i.v. and then with apraclonidine 1% eye drops. In one group of rabbits, the penetration into the aqueous humor of Evans blue injected intravenously was also studied. Evans blue content in aqueous humor was 0.03 +/- 0.08 mg/100 ml in control rabbits; 0.92 +/- 0.53 mg/100 ml in placebo rabbits treated by laser; and 0.28 +/- 0.19 mg/100 ml in apraclonidine rabbits treated by laser. Apraclonidine eye drops led to a decrease in IOP and prevented IOP rise following argon laser application. Placebo treated rabbits had a 20% increase in IOP following laser application. Apraclonidine-treated eyes showed mydriasis and blanching of the conjunctiva. These effects were not affected by pretreatment with dapiprazole or yohimbine. In these experiments, the treatment with apraclonidine 1% eye drops completely protected the blood aqueous barrier from the disruption caused by laser burning of the iris. The protection was less effective when apraclonidine was applied after laser burnings.

Evaluation of Laser Flare-cell Photometry in the Appraisal and Management of Intraocular Inflammation in Uveitis

Laser flare-cell photometry enables objective and quantitative measurement of anterior chamber inflammation. Systematic data currently are used mainly for clinical research; few are yet available in uveitis. The authors prospectively studied the amount, duration, and pattern of inflammation for well-defined uveitic conditions and evaluated the potential usefulness of laser flare-cell photometry in uveitis. Mean initial flare was calculated in HLA-B27-positive acute anterior uveitis, acute herpes zoster uveitis, acute retinal necrosis (ARN), Fuchs heterochromic cyclitis, intermediate uveitis (pars planitis-type), posterior sarcoidosis, posterior pole toxoplasmosis, and birdshot chorioretinopathy. Evolution of aqueous flare and cells was analyzed for acute anterior uveitis, ARN, and pars planitis treated for cystoid macular edema (CME), all of which received a standardized therapy. Blood-aqueous barrier disruption was very pronounced in acute anterior uveitis (170.2 +/- 33 photons/msecond), ARN (177.4 +/- 88 photons/msecond), moderate in posterior sarcoidosis (38.1 +/- 11 photons/msecond), acute zoster uveitis (25.8 +/- 6.1 photons/msecond), and pars planitis (19.1 +/- 2.9 photons/msecond) but only minimal in Fuchs heterochromic cyclitis (10.2 +/- 3.5 photons/msecond), toxoplasmosis (9.0 +/- 1.2 photons/msecond) and birdshot chorioretinopathy (5.7 +/- 1.1 photons/msecond). For acute anterior uveitis, ARN, and pars planitis with CME, the inflammatory patterns were determined. The potential of laser flare-cell photometry for precise follow-up and adjustment of therapy was illustrated in cases of anterior and posterior uveitis. The authors' findings show that laser flare-cell photometry allows quantitative assessment of inflammation in uveitis and contributes to improved management of patients with uveitis.

Serum albumin enters the posterior chamber of the eye permeating the blood-aqueous barrier

In order to check the entrance site of serum albumin into the aqueous humor, rabbits were injected intravenously either with Evans blue (which reacts very quickly with albumin) or horseradish peroxidase. The Evans blue-albumin complex (Eb-a) was traced to the posterior chamber as early as 1 min after injection by examining frozen half eyes. The Eb-a was localized in frozen sections by fluorescence microscopy in the stroma of the ciliary and iridial processes, as well as in the lumen of all blood vessels from 1 to 60 min after injection even at doses as low as 3 mg/kg. The peroxidase activity was also localized on these same structures from 8 min to 4.5 h. Neither tracer was visualized in the iris stroma outside the lumen of blood vessels. This was also true for experiments with Eb (75 mg/kg) in which the blood-aqueous barrier was disrupted. The concentration (m/v) of Evans blue and the peroxidase activity in the aqueous humor of the anterior chamber were estimated by spectrophotometry. The morphological integrity of the blood-aqueous barrier was demonstrated by electron microscopy in all peroxidase-injected rabbits. Considering that (a) the Eb-a appeared first in the posterior chamber, (b) there was a high concentration of tracers in the stroma of the ciliary and iridial processes, (c) neither tracer was visualized in the iris stroma, (d) there was no evidence of disruption of the blood-aqueous barrier, and (e) the concentration of both tracers in the aqueous humor kept increasing up to 4 h after injection, it was assumed that serum macromolecules entered first the posterior chamber and subsequently migrated to the anterior chamber. Most likely they passed in between the cells of the inner layer of the ciliary epithelium, the site of the so-called blood-aqueous barrier. No evidence was found indicating migration of macromolecules from the stroma of the processes directly to the anterior chamber via the iris root.

Flurbiprofen 0.03% for the control of inflammation following cataract extraction by phacoemulsification

We conducted a double-masked, vehicle-controlled study to evaluate the anti-inflammatory effect of topical flurbiprofen in cataract surgery by phacoemulsification and implantation of a posterior chamber intraocular lens. The 233 patients were randomized to receive either flurbiprofen or vehicle immediately prior to and for two weeks following surgery. No concomitant corticosteroid use was allowed. The flurbiprofen group had significantly less anterior chamber cells and flare at day 7 and significantly less conjunctival erythema, corneal edema, and lid edema at day 14. The investigator's global effectiveness rating was higher in the flurbiprofen group at day 14. Blood-aqueous barrier disruption, as measured by aqueous fluorophotometry, was statistically significantly diminished in the flurbiprofen group. Burning and stinging were rated significantly greater in the flurbiprofen group than in the vehicle group. Foreign-body sensation and photophobia were significantly more severe in the vehicle group than in the flurbiprofen group. Flurbiprofen provided postsurgical anti-inflammatory efficacy in clinical signs of inflammation and in blood-aqueous barrier disruption, and also showed improved subjective signs.

Blood-Aqueous Barrier in Eyes with Retinal Vein Occlusion

The purpose of this study is to examine the changes of blood-aqueous barrier function in cases of central or branch retinal vein occlusion. In addition to fluorophotometry of the aqueous humor and posterior vitreous, the authors used a method that quantifies protein in the aqueous (aqueous flare) by measuring the intensity of scattered laser light. Aqueous and posterior vitreous fluorescein concentrations and aqueous flare were significantly higher than in unaffected fellow eyes or eyes of visually normal age-matched controls both in central and branch retinal vein occlusions. They also were significantly higher in eyes with central vein occlusion than in those with branch vein occlusion. Among those eyes with central vein occlusion, aqueous and posterior vitreous fluorescein concentrations and aqueous flare were significantly higher in the hemorrhagic than in the venous stasis type of disease. Among eyes with branch vein occlusion, cases at the acute stage showed significantly higher amounts of aqueous and posterior vitreous fluorescein concentrations and aqueous flare than did those with chronic occlusion. The authors believe that increased amounts mainly reflect blood-ocular barrier disruption. Not only the blood-retinal barrier but also the blood-aqueous barrier disruption is a common sequela in the disorder.

Leukotrienes and sensory innervation in blood-aqueous barrier disruption in the dog.

The effect of a specific 5-lipoxygenase inhibitor, PF5901 (5% in corn oil), on disruption of the blood-aqueous barrier (BAB) in the dog was investigated using a unilateral mild paracentesis model. BAB breakdown was quantitated using anterior chamber fluorophotometry. Fluorescence in the eyes of the PF5901 group was not statistically significantly different (P greater than 0.05) from that in the vehicle group. A tendency towards greater fluorescein concentrations was noted in the PF5901 treated eyes. It was concluded that leukotrienes are not important mediators of BAB disruption in this model and that leukotriene inhibitors may actually exacerbate disruption due to shunting of arachidonate metabolism towards the cyclooxygenase and/or epoxygenase pathways. In a second experiment, the effects of proparacaine and flurbiprofen were evaluated on blood-aqueous barrier disruption and pupil size following a more severe paracentesis. Flurbiprofen dampened both barrier disruption and the miotic response but proparacaine suppressed neither reaction, suggesting that, in the dog, prostaglandins are more important mediators of the ocular irritative response than are sensory neuropeptides.

Fluorophotometric evaluation of experimental blood-aqueous barrier disruption in dogs

Summary A protocol for performing slit-lamp fluorophotometry of the anterior chamber in dogs was established. The technique was then used to develop a model of blood-aqueous barrier disruption that can be used for comparative testing of ophthalmic anti-inflammatory drugs. It was determined that barrier disruption induced by a slow, controlled paracentesis of a small volume of aqueous humor may provide the most reliable model for drug testing. Additionally, fluorophotometry proved to be a sensitive and accurate means of detecting breakdown of the blood-aqueous barrier.

Treatment of glaucoma by use of transscleral neodymium:yttrium aluminum garnet laser cyclocoagulation in dogs

Summary Neodymium:yttrium aluminum garnet (Nd:yag) laser energy was transsclerally applied to the ciliary body of 56 eyes of 37 dogs for treatment of glaucoma. Forty-four eyes were glaucomatous at the time of treatment, and 12 normotensive eyes with ciliary cleft closure were treated prophylactically. Glaucoma was primary in 35 dogs and secondary in 2 dogs (1 eye in each dog). Energy was delivered by a general surgical Nd:yag laser via a hand-held, 600-µc-diameter flexible quartz fiber. The mean (±sd) number of spots treated per eye was 35 (±9.7), with mean energy per burst of 7.1 (±2.6) J; mean total energy delivered to the eyes was 228 (±81) J. Follow-up evaluation was available for 42 eyes from 2 to 4 weeks after treatment, and for 32 eyes from 12 to 24 weeks after treatment. Treatment success, defined as maintenance of intraocular pressure <25 mm of Hg, was achieved in 83% (20/24) of glaucomatous eyes evaluated between 12 and 24 weeks of treatment. Of 4 treatment failures, 3 were eyes devoid of uveal pigment. The consistent acute effects of treatment were conjunctival vascular congestion and blood-aqueous barrier disruption, recognized clinically by the presence of aqueous flare. Hyphema developed in 16% (9/56) of eyes; hyphema resolved without complication in all but 2 eyes. A common long-term complication of treatment was cataract formation, recognized in 37% (12/32) of eyes evaluated at 12 to 24 weeks. Cataracts were sufficiently dense to obstruct vision in 4 eyes. Phthisis bulbi was observed in 1 eye. Results of this study indicate that Nd:yag laser cyclocoagulation is an effective means of controlling intraocular pressure in dogs with glaucoma. Cataract formation is a potential complication of treatment.

Effect of indomethacin and prednisolone on the disruption of the blood-aqueous barrier after hyperthermia on the rabbit eye by focused ultrasound.

In 24 rabbits both eyes were treated in the perilimbic area with hyperthermia by focussed ultrasound at a frequency of 4.65 MHz. The intra-ocular pressure (IOP) decreased significantly in all eyes. The effect of pre-treatment with indomethacin and prednisolone on the inflammatory response induced by the insonification was assessed by determination of protein in the aqueous humour 2 h after ultrasound treatment. Local pre-treatment with indomethacin but not with prednisolone was followed by less increase in protein concentration of the aqueous humour as compared to placebo-treated controls. The IOP was not influenced significantly by the drug pre-treatments.

Anterior segment fluorophotometry in acute anterior uveitis.

Anterior segment fluorophotometry was used to assess the severity of blood-aqueous barrier disruption in 25 patients with acute anterior uveitis. The results indicated that HLA-B27-positive patients had a more severe inflammation than did HLA-B27-negative patients, which was not discernible when judged by clinical signs and symptoms. Follow-up studies showed that the blood-aqueous barrier was disturbed for longer than the clinical signs indicated, and sometimes a temporary subclinical relapse was demonstrated on early withdrawal of topical therapy. The blood-aqueous barrier appeared to be restored after each attack of acute anterior uveitis in the majority of patients, with no evidence of progressive damage from repeated attacks. Our results indicated that fluorophotometry provides an objective and sensitive method of assessing anterior uveitis.

Effect of ACTH on the composition of the aqueous humour of the rabbit eye.

Tetracosactide (Synacthen, Ciba) increases the concentration of corticosterone in the aqueous humour of the rabbit eye. The maximal increase, about 5-fold of the basal level, occurs with a slight delay of approximately 30 min after the maximally stimulated corticosterone level in blood plasma. Glucocorticoid elevation is paralleled by an increase of protein content and a slight rise of glucose in aqueous. A disruption of the blood-aqueous barrier by ACTH similar to the action of alpha-melanocyte-stimulating hormone is suggested.

Drug prevention of blood-aqueous barrier disruption.

In order to evaluate the anti-inflammatory effect of non-steroidal compounds on the eye, we tested them in rabbits using the inhibitory effect on paracentesis-induced disruption of the blood-aqueous barrier. Protein and--after intravenous-injection--fluorescein were determined in punctates of aqueous humor. Indomethacin, flurbiprofen and diclofenac in a 0.01% solution showed a marked inhibitory effect, which lasted for 24 h. Addition of polysorbate to eye drugs diminished the inhibitory effect.

Disruption of iridial blood-aqueous barrier in experimental diabetic rats.

The permeability pattern of iridial blood-aqueous barrier in streptozotocin-diabetic rats, maintained for 1-6 months, was studied with the light and electron microscopes, using horseradish peroxidase as a tracer. A reaction product of horseradish peroxidase was confined to the vascular lumina and to a small number of vesicles on the luminal portion of the endothelial cells in control rats and diabetic rats maintained for 1 month. In diabetic rats maintained for 2-6 months, endothelial cells contained a large number of horseradish peroxidase-labeled vesicles which opened into the basement membrane, and intercellular junctions of the endothelial cells were filled with horseradish peroxidase. Horseradish peroxidase was consistently found in the stroma around the vessels, and seemed to reach the anterior chamber through the intercellular spaces between the fibroblasts. However, the passage of horseradish peroxidase was blocked by the posterior epithelial cells.