Recovery of the blood-aqueous barrier after cataract surgery.

Following extracapsular cataract and posterior chamber implant surgery the sequential recovery of the blood-aqueous barrier was measured by anterior segment fluorophotometry. Postoperatively 49 (69.0%) out of 71 eyes (71 patients) had recovered at a uniform rate, re-establishing a normal blood-aqueous barrier by the end of the three-month study. In these eyes recovery of the blood-aqueous barrier was unaffected by the use of preoperative indomethacin, the surgeon, the type of section, or the type of fixation of the implant. In eyes recovering normally after cataract surgery the rate of recovery of the blood-aqueous barrier can be expressed by a in the equation a = (y-b)/x, in which y is the logarithm of the anterior chamber fluorescence, x is the time after surgery, and b is a constant for each patient which is the anterior chamber fluorescence measured immediately after surgery. This normal rate of recovery provides a baseline from which to assess surgical technique or postoperative medication.     

The effect of timolol maleate on the disruption of the blood-aqueous barrier in the rabbit eye

A disruption of the blood-aqueous barrier in rabbit eyes was elicited by use of topical prostaglandin E2(PGE2), infrared irradiation of the iris, or by subcutaneous alpha-melanocyte-stimulating hormone (alpha-MSH). The aqueous flare provoked was measured quantitatively with a photoelectric instrument. The effect of the (topical) beta-adrenergic antagonist timolol maleate on the breakdown of the blood-aqueous barrier was tested. Timolol applied topically in very large doses had no effect on exogenously administered PGE2. However, even in a very small concentration applied topically, timolol reduced the flare response to both infrared irradiation and alpha-MSH. These results support the theory that the effect of alpha-MSH and infrared irradiation on the blood-aqueous barrier is dependent on intact beta-adrenergic receptor sites.     

Prolonged monitoring of the blood-aqueous barrier with fluorescein-labeled albumin

Aqueous fluorophotometry has proved to be a useful indicator of changes in the blood-aqueous barrier after surgical, immunologic, or laser manipulations. Previously used fluorescent tracers have been unable to follow rapid changes continuously in the blood-aqueous barrier. Fluorescein-labeled homologous serum albumin, however, provides extremely stable and high plasma levels of fluorescence due to active renal reabsorption with very low levels in the normal aqueous because of its high molecular weight. This feature allows prolonged, continuous, and highly sensitive monitoring of the blood-aqueous barrier before, during, and after a manipulation. The usefulness of this technique is demonstrated in a model that has been well studied with other methods: the response to argon laser iris photocoagulation.     

Collapse of the blood-aqueous humor barrier following laser injury--preventive pharmacotherapy with prostaglandin inhibitors

Laser-induced collapse of the blood-aqueous barrier and the protective effect of different prostaglandin inhibitors were investigated in the animal study reported here. As a parameter of the barrier function, the protein concentration in the aqueous humor was measured using a micromethod. The anterior chamber of 90 eyes (45 rabbits) was tapped only once, 100 min after the laser procedure. The results prove that different prostaglandin inhibitors in a systemic or topical application form can effectively reduce disturbances of the blood-aqueous barrier after laser surgery. This is also of clinical relevance with regard to laser iridotomy or trabeculoplasty in glaucoma.     

Morphological study of the disruption of the blood-aqueous barrier following paracentesis

Long-term morphological changes of the blood-aqueous barrier following paracentesis were studied in monkeys. Horseradish peroxidase molecules given intravenously were detected in the intercellular space beyond the tight junction between the nonpigmented ciliary epithelial cells in a monkey 7 days after the operation. The data demonstrated that the breakdown of the blood-aqueous barrier was not functionally repaired 7 days after the operation. Cysts were observed at the most anterior portions of the ciliary processes in monkeys surviving for 14 days to 1 year. These cysts consisted of two layers of both pigmented and nonpigmented epithelial cells. These findings suggest that the breakdown of the blood-aqueous barrier remains not to be repaired for log periods.     

CGRP in relation to neurogenic inflammation and cAMP in the rabbit eye

The effects of topical application of neutral formaldehyde (1%) and intracameral administration of calcitonin gene-related peptide (CGRP, 0.5- or 2.0 micrograms) on the intraocular pressure (IOP), blood-aqueous barrier, pupil size, blood pressure and cyclic AMP (cAMP) content in the aqueous humour of a rabbit were studied. Topical chemical irritation with 1% formaldehyde caused a typical irritative response in the eye with a rise in the IOP, breakdown of the blood-aqueous barrier and miosis. The cAMP content in the aqueous humour was also increased (88.5 +/- 35.0 pmol ml-1, P less than 0.05) when compared with the control group (16.3 +/- 3.6 pmol ml-1). Intracameral administration of CGRP caused a rise in the IOP, breakdown of the blood-aqueous barrier and also systemic hypotension. Miosis was not observed after intracameral CGRP but an increase in the cAMP content in the aqueous humour was seen (130.5 +/- 30.3- and 158.7 +/- 48.1 pmol ml-1, both P less than 0.01, after 0.5 or 2.0 micrograms, respectively). The cAMP concentration in the aqueous humour after topical chemical irritation and intracameral CGRP correlated with the intensity of the breakdown of the blood-aqueous barrier. CGRP seems to cause most, but not all, of the ocular changes after sensory nerve stimulation elicited by topical neutral formaldehyde. Of these CGRP-induced changes, only the breakdown of the blood-aqueous barrier is related to an increase in the cAMP content in the aqueous humour. Contralateral responses after sensory nerve stimulation were similar to contralateral responses to intracameral CGRP.     

The effects of 3-isobutyl-methyl-xanthine on experimentally induced ocular inflammation in the rabbit

The effect of topical administration of 3-isobutyl-methyl-xanthine (IBMX), a potent phosphodiesterase inhibitor, was studied on an experimentally provoked uveitis in rabbits. After presensitization with an intravitreal injection of human serum albumin (HSA), intravenous antigenic challenge induces blood-aqueous barrier breakdown and leukocyte infiltration. The effect of IBMX on the blood-aqueous barrier was determined by scoring the severity of the flare in the anterior chamber and by determination of the levels of ascorbic acid and protein in the aqueous. Treatment with IBMX 1% two times daily, significantly inhibited the breakdown of the blood-aqueous barrier and the increase in PGE2 level of the aqueous humor. There was no effect on leukocyte infiltration. The therapeutic effect of IBMX in blood-aqueous barrier protection is comparable with the effect of topical treatment with the corticosteroid medrysone.     

Systemic aspirin and indomethacin do not prevent the response of the monkey eye to trauma.

The stability of the blood-aqueous barrier of the monkey eye was challenged by three different methods: anterior chamber paracentesis, intravitreal shigella endotoxin, and subconjunctival arachidonic acid. Systemic aspirin and indomethacin were ineffective in stabilizing the blood-aqueous barrier in all three of these systems.     

Fluorophotometry as a method for the detection of permeability changes in the blood and aqueous humor barrier

The increase in permeability of the blood-aqueous barrier after Nd-YAG laser iridotomy and the protective effect of locally applied indomethacin were investigated in an experimental animal study using a computerized fluorophotometer. The permeability of the blood-aqueous barrier was evaluated by three different molecules: fluorescein-sodium (molecular weight 330), fluorescein-labeled dextran 70 000 (molecular weight 70 000) and fluorescein-labeled dextran 150 000 (molecular weight 150 000). The fluorescein concentration of the anterior chamber was measured in 36 eyes (18 rabbits) as well as in a control group of 9 eyes (9 rabbits) at fixed times after intravenous dye injection. Fluorescein leakage occurred, but no leakage of fluorescein-labeled dextrans was visible in the control group. Laser iridotomy induced a time-dependent increase in anterior segment permeability to fluorescein and fluorescein-labeled dextrans. Disturbance of the blood-aqueous barrier was effectively reduced by topical pretreatment with indomethacin, which mainly inhibited the leakage of the fluorescein-labeled dextrans. The clinical relevance of the laser-induced breakdown of the blood-aqueous barrier and the protective effect of a prophylactic pharmacotherapy are discussed.     

Intraocular effects of substance P in the rabbit

The intraocular effects of substance P (SP) were studied in rabbits by measuring the pupil diameter, intraocular pressure (IOP), and aqueous humor protein concentration. Most of the animals were pretreated with indomethacin to avoid any interaction with prostaglandins. Intracameral injection of 1 to 150 ng of SP caused strong and persistent miosis without appreciably affecting the aqueous humor protein concentration or IOP. Intracameral injection of 0.8 to 11 micrograms of SP also induced an increase in IOP (7 to 8 mm Hg) without any apparent concomitant disruption in the blood-aqueous barrier. Outflow facility of aqueous humor decreased by a mean value of 50% after intracameral injection of 0.8 to 1.5 microgram of SP. Since the increase in IOP could be prevented by iridectomy, it was probably caused by a pupillary block from the intense miosis induced by SP. No disruption in the blood-aqueous barrier could be detected after intra-arterial infusion of 10 micrograms of SP or intravitreal injection of 100 ng of SP, indicating that the ciliary epithelium was practically insensitive to exogenous SP. Topical as well as subconjunctival administration of up to 1 mg of SP did not cause any irritative response in the eye. The results show that with concentrations of SP causing intense miosis, the eye does not exhibit visible hyperemia and disruption of the blood-aqueous barrier. This finding is consistent with the hypothesis that after certain irritative stimuli, miosis is mediated by a pathway separate from the hyperemia and disruption of the blood-aqueous barrier.     

Breakdown of the blood--aqueous barrier in the rabbit eye by infrared radiation

Breakdown of the blood-aqueous barrier was produced by infrared radiation (IR) at a heat flux from 24 to 44 J/cm2 in pigmented, but not in albino rabbits. Blood-aqueous barrier breakdown was inhibited by indomethacin and ketamine/xylazine anesthesia mixtures, but not by [D-Trp2,D-Pro7,9]-substance P. The degree of blood-aqueous barrier breakdown could be controlled by IR flux. Two models for accurate determination of the heat flux are presented.     

Indomethacin and the epinephrine-induced breakdown of the blood-ocular barrier in rabbits

Using aqueous and vitreous fluorophotometry, the authors examined the blood-aqueous and blood-retinal barrier functions in three groups of pigmented rabbits. Epinephrine (1.25%) was applied topically five times daily and indomethacin (0.5% sesame oil suspension) was applied topically three times daily to one eye of each of the animals in Group 1; under the same regimen, epinephrine and indomethacin placebo were administered to one eye of each of the animals in Group 2 and epinephrine placebo and indomethacin placebo were administered to one eye of each of the animals in Group 3. Fluorophotometry was done 1, 2, and 3 months after drug administration. The results showed that epinephrine induced disruption of the blood-aqueous barrier 2 and 3 months after drug administration, and that the magnitude of this disruption increased with time. Epinephrine also induced disruption of the blood-retinal barrier 3 months after drug administration. Indomethacin significantly prevented disruption of the blood-aqueous barrier at 2 and 3 months and significantly prevented disruption of the blood-retinal barrier at 3 months. The magnitudes of the barrier disruptions in eyes treated with both epinephrine and indomethacin were slightly higher than, or the same as, those of the control eyes. The results strongly indicated that the epinephrine-induced disruption of the blood-ocular barrier was partially caused by prostaglandins and other cyclo-oxygenase products whose biosynthesis was initiated by epinephrine.     

Effect of intraocular lens fixation on the blood-aqueous barrier

We used slit-lamp fluorophotometry to evaluate the influence of various intraocular lens fixation sites on the blood-aqueous barrier in 106 eyes. After an average follow-up period of 1.1 years, eyes with anterior chamber lenses with closed or rectangular loops had a significantly higher concentration of fluorescein than did eyes with other types of implants (P less than .1 to P less than .001). In eyes with posterior chamber lenses, those with ciliary sulcus fixation had a significantly higher concentration of fluorescein than did those with intracapsular fixation (P less than .02). Compared with aphakic eyes without implants, eyes with any implant other than posterior chamber lenses with intracapsular fixation had significantly higher fluorescein concentrations (P less than .02 to P less than .001). These results indicated that the flexibility and the intraocular location of the lens loops are significant factors in securing the integrity of the blood-aqueous barrier of pseudophakic eyes. Posterior chamber lenses with intracapsular fixation caused the least trauma to the blood-aqueous barrier.     

超声乳化白内障吸除术对血-房水屏障功能的影响

目的　观察小切口超声乳化白内障吸除人工晶状体植入术及相关因素对血 房水屏障功能的影响。方法　使用激光蛋白细胞检测仪对 60例 (64只眼 )白内障患者超声乳化白内障吸除人工晶状体植入术前、后的房水蛋白浓度进行定量检测 ,记录并比较闪光值。术后随访时间为 3个月。结果　超声乳化白内障吸除人工晶状体植入术前 ,术后 1d、1周、1个月及 3个月术眼房水的平均闪光值分别为 (6 94± 0 3 4 )、(2 6 2 7± 1 3 7)、(13 96± 1 0 5)、(9 0 7± 0 43 )及 (7 16± 0 2 7)光粒子数 /ms ,其中术后 1d、1周及 1个月高于术前 ,且差异均有显著意义 (P <0 0 5) ;术后 3个月与术前比较 ,差异无显著意义 (P >0 0 5)。术后早期术眼房水蛋白浓度与患者年龄呈正相关 (r =0 40 0 ,P =0 0 0 1) ,与患者的性别和眼别均无相关。术中虹膜脱出者术后 1d和 1周血 房水屏障功能破坏严重。结论　超声乳化白内障吸除人工晶状体植入术在术后短期内影响术眼的血 房水屏障功能 ;激光蛋白细胞检测仪可动态评价超声乳化白内障吸除术对血 房水屏障功能的影响。 (中华眼科杂志 ,2 0 0 4,40 :2 6 2 9)     

Effects of anterior chamber irrigation and irrigating solutions on the blood aqueous barrier

Anterior chamber irrigation and irrigating solutions were evaluated for their possible damaging effects on the blood-aqueous barrier. Rabbit anterior chamber was irrigated with physiological saline, lactated Ringer solution, balanced salt solution (BSS) and S-MA2 using the irrigation aspiration tip of Cavitron Kelman phacoemulsifier. Fluorophotometry was performed to evaluate the function of the blood-aqueous barrier. Physiological saline yielded the most severe damage, and lactated Ringer solution and BSS yielded moderate damage in blood aqueous barrier, while S-MA 2 showed only slight damage to barrier function. These results suggest that HCO^–3 and glucose, as well as Ca⁺⁺, Mg⁺⁺ and the buffer system, are essential constituents for maintaining function in the blood-aqueous barrier.     

Quantification of the ocular response to treatment in posterior uveitis.

Twenty patients with posterior uveitis were studied by anterior segment fluorophotometry to determine whether there was a relationship between the degree of breakdown of the blood-aqueous barrier and the clinical recovery of posterior uveitis. In individual eyes the degree of breakdown and recovery of the blood-aqueous barrier (as measured by changes in the anterior chamber fluorescein concentration) followed the resolution and relapse of disease making it possible to quantify the ocular response to treatment.     

The continuous and quantitative observation of permeability changes of the blood-aqueous barrier in allergic inflammation of the eye

Permeability changes of the blood-aqueous barrier were studied in the eyes of rabbits subjected to immunologic inflammation. The changes were investigated by slit-lamp microphotometers. The leakage of fluorescein-labeled rabbit serum albumin into the anterior chamber was observed in eyes inflamed by reverse passive Arthus reactions. The permeability of the blood-aqueous barrier changed in biphasic pattern in allergic inflammations; the first phase began 5 min after the antigen challenge and lasted for 1 hr, followed by the late phase at which the dye concentration reached a peak 2 hr after the challenge and then gradually decreased.     

Effect of neurogenic irritation and calcitonin gene-related peptide (CGRP) on ocular blood flow in the rabbit

The effects of sensory nerve stimulation (topical neutral formaldehyde, 1%) and intracameral injection of calcitonin gene-related peptide (CGRP) on regional ocular blood flow, intraocular pressure (IOP), the blood-aqueous barrier, pupil size, and blood pressure were studied in the rabbit. Sensory nerve stimulation elicited a typical irritative response in the rabbit eye, with vasodilation in the ciliary body (from 128 +/- 31 to 363 +/- 105 mg/min, p less than 0.05) accompanied with a breakdown of the blood-aqueous barrier, rise in the IOP, and miosis. CGRP caused similar, but not identical, changes in the eye: vasodilation in the ciliary body (from 60 +/- 14 to 258 +/- 75 mg/min, p less than 0.05), breakdown of the blood-aqueous barrier and rise in the IOP, accompanied with systemic hypotension. Miosis was not observed after CGRP. In the present study, the vasodilatory action of CGRP on the rabbit eye has been shown. This makes our understanding of the mechanism of the ocular irritative response after sensory nerve stimulation more complete. Thus, CGRP through vasodilation disrupts the blood-aqueous barrier and raises the IOP. The more intense increase in the IOP after sensory nerve stimulation than after CGRP is probably caused by a CGRP-induced vasodilation and breakdown of the blood-aqueous barrier, enhanced by a miosis-induced pupillary block.     

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 I 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.     

Long-term endothelial cell loss and breakdown of the blood-aqueous barrier in cataract surgery

Progressive endothelial cell loss and endothelial cell loss induced at the time of surgery occurs in all eyes with rigid anterior chamber intraocular lenses (IOLs). Eyes with surgical tuck or late ovaling of the pupil following surgery have greater yearly rates of cell loss than eyes that have no complications. This progressive loss may be related to chronic uveitis from iris chafing by the implant or to direct mechanical damage to the corneal endothelium. We have demonstrated that fluorophotometry shows chronic damage to the blood-aqueous barrier in all eyes with rigid anterior chamber IOLs, but this does not correlate with the degree of endothelial cell loss. Our results suggest there is damage to the blood-aqueous barrier and to the corneal endothelium, but the damage to the latter influences progressive endothelial cell loss.