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.     

Effects of pilocarpine and tropicamide on blood-aqueous barrier permeability in man.

The time courses of changes in the effects of topical pilocarpine and tropicamide on the index of the blood-aqueous barrier permeability to plasma protein (Pin) were determined in normal volunteers. Before and after drug instillation in one eye, protein concentration in the anterior chamber (Ca) was determined from aqueous flare intensity with a laser flare-cell meter and from aqueous flow by fluorophotometry. The Pin was calculated from the Ca, plasma protein concentration, and aqueous flow. One percent pilocarpine produced a maximum increase of 21 +/- 10% in the Ca (mean +/- SEM, n = 10), no significant change in the aqueous flow (n = 5), and a maximum increase of 29 +/- 10% in the Pin (n = 10). Three percent pilocarpine produced a maximum increase of 55 +/- 11% in the Ca (n = 8), a maximum increase of 34 +/- 13% in the aqueous flow (n = 5), and a maximum increase of 74 +/- 18% in the Pin (n = 8). Tropicamide (0.4%) produced a maximum decrease of 17 +/- 7% in the Ca (n = 8), a maximum decrease of 15 +/- 11% in the aqueous flow (n = 8), and a maximum decrease of 24 +/- 13% in the Pin (n = 8). The results indicated that pilocarpine increased the blood-aqueous barrier permeability to plasma protein in a dose-dependent manner and that tropicamide reduced it.     

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)     

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.     

Topical timolol and blood-aqueous barrier permeability to protein in human eyes]

The effect of topical 0.5% timolol on the permeability of the blood-aqueous barrier to plasma protein was studied in ten young normal volunteers. Before and after instillation of timolol in one eye, simultaneous measurements of aqueous flow rate, f(t), by fluorophotometry and protein concentration in the anterior chamber, Ca(t), with a laser flare-cell meter were made in both eyes at hourly intervals. The coefficient of protein entry into the anterior chamber was calculated using an equation formulating protein dynamics in the anterior chamber from the changes in f(t), Ca(t), and plasma protein concentration. The Ca(t) in the treated eye showed a maximum increase of 37 +/- 4% (mean +/- SEM) as compared with that in the fellow eye 5 hours after instillation, while the f(t) in the treated eye showed a maximum reduction of 30 +/- 4% 2 hours after instillation. The intraocular pressure in the treated eye showed a maximum reduction of 3.0 +/- 0.3 mmHg 2 hours after instillation. No significant changes were found in the coefficient of protein entry in the anterior chamber between before and after timolol instillation or between timolol-treated and fellow untreated eyes. These results indicated that topical 0.5% timolol does not affect the permeability of the blood-aqueous barrier to plasma protein significantly.     

Disruption of the blood-aqueous barrier following paracentesis in the rabbit

The concentrations of protein and prostaglandin are greatly elevated in aqueous humour secondary to anterior chamber paracentesis in the rabbit. A transient increase of intraocular tension which follows paracentesis is mediated by prostaglandin and the breakdown in the blood-aqueous barrier is at least partly mediated by this autacoid. Using a fluorescein angiographic technique the bulk of the plasmoid aqueous was shown to enter the anterior chamber through the pupil and not from the surface of the iris. Furthermore, the capillary beds of the ciliary processes, but not of the iris, took up intravenously-injected colloidal carbon indicating that the ciliary vessels became excessively permeable. The present evidence indicates that the site of disruption of the blood-aqueous barrier occurs within the ciliary processes and not in the iris.     

匹罗卡品对兔眼葡萄膜巩膜途径作用的形态学研究

目的：从形态学方面探讨匹罗卡品对兔眼葡萄膜巩膜途径的作用。方法：通过前房内注入微量示踪剂异硫氰酸荧光素牛血清白蛋白（Fluorescein isothiiocyanate-bovine serum albumin,FITC-BSA),匹罗卡品点眼后2,4,6,8,10和12h各处死家兔2只,摘除眼球作冰冻切片,于荧光显微镜下观察并确定睫状体、脉张膜上腔、前、后巩膜和脉络膜的荧光强度等级,并于光镜下观察其组织结构改变。结果：匹罗卡品点眼后眼压下降,点眼后睫状体、脉络膜上腔和前巩膜荧光强度均显著减弱,后巩膜、脉络膜无明显变化。光镜观察见睫状肌细胞间隙缩小。结论：匹罗卡品通过收缩睫状肌而减少房水从葡萄膜巩膜途径排出。     

Evaluation of therapeutic effectiveness using MR imaging in a rabbit model of anterior uveitis

Magnetic resonance imaging (MRI) has been used to examine conditions that alter the permeability of the blood-retinal barrier. Our goal was to determine if blood-aqueous barrier permeability could be similarly assessed, because MRI offers the theoretical advantage of providing quantitative data directly from inflamed uveal tissues rather than from the aqueous humor into which the inflammatory reaction spills. As an additional challenge, we sought to use MRI to measure differences between the inflamed uveal tissues of corticosteroid-treated and placebo-treated uveitic eyes. Anterior uveitis was induced in one eye of eight rabbits by subcutaneous injection of Mycobacterium tuberculosis, followed after 10 days with intravitreal challenge. One rabbit of each pair was treated with topical 1% prednisolone acetate while control rabbits were treated with artificial tears. Contrast-enhanced MRI studies were performed prior to uveitis induction, one day after induction and then weekly for at least 2 weeks. MR image data were analyzed to determine percent change in peak enhancement of the ciliary body and anterior chamber. The initial rate of change of enhancement of the anterior chamber was also measured. Extensive contrast agent-induced MR image enhancement of both the anterior chamber and the ciliary processes was measured following the induction of uveitis. More rapid improvement was measured for the 1% prednisolone acetate-treated rabbit eyes (P < 0.001). MR signal enhancement data obtained from the ciliary processes proved to be the most reliable indicator of disease activity in this rabbit model of uveitis. Such data can only be obtained using MRI.     

对比增强磁共振在虹膜周边切除术后兔眼前后房屏障研究中的作用

背景 眼前后房间是否构成血—眼屏障的一部分一直存有争议,传统的检测方法由于不能测量后房房水的情况而无法提供更好的证据.目的 使用对比增强磁共振成像(MRI)研究兔眼虹膜周边切除术后造影剂在前后房的分布,证实眼前后房之间的屏障作用.方法 8只清洁级新西兰白兔单眼接受虹膜周边切除术,对侧眼为对照眼.MRI的造影剂钆喷酸葡胺(Gd-DTPA)作为示踪剂,在活体兔耳缘静脉注射0.5 mol/L造影剂0.2 ml/kg,MRI连续扫描,观察造影剂的渗透性及眼内分布,通过感兴趣区时间相关的信号增强率分析影像.结果 兔耳缘静脉注射0.2 ml/kg Gd-DTPA后,双眼睫状体信号在10 min内快速增强,且手术眼的荧光强度强于对照眼.Gd-DTPA注射后30～40 min睫状体信号最强,此后逐渐下降,前房信号逐渐增强,手术眼后房信号增强,而对照眼后房呈低信号,Gd-DTPA注射后感兴趣区分别为睫状体、前房和后房,手术眼后房信号增强与前房同步,对照眼后房未发现信号增强.结论 血浆蛋白进入前房途径与房水分泌途径是分别独立的通道,眼前后房之间存在着屏障,是血—眼屏障的组成部分.     

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.     

Medical treatment of crystalline lens dislocation into the anterior chamber in a patient with Marfan syndrome

We report the case of a 32-year-old male with spontaneous crystalline lens dislocation into the anterior chamber with corneal touch and increased intraocular pressure. The case was handled in a conservative way: before bringing the patient to supine position, pharmacological pupil dilation with tropicamide plus phenylephrine was performed. One drop was instilled every 15?min for 1?hour. Once the posterior displacement of the lens behind the iris was confirmed, 2?% pilocarpine was used to reverse pupil dilation. The patient remained on topical 2?% pilocarpine and 5?% sodium chloride solution.     

Effect of apraclonidine on blood-aqueous barrier permeability to plasma protein in man.

Effect of a single instillation of 30 microliters 0.5% apraclonidine on the coefficient of protein entry (k(in)), a quantitative index of blood-aqueous barrier permeability, was determined in ten normal volunteers. Before and after administering the drug to one eye and the vehicle to the other eye of a subject, protein concentrations in the anterior chamber were measured using a laser flare-cell meter. One week later, aqueous flow rate was determined by fluorophotometry under the same experimental conditions. The k(in) was calculated from protein concentrations in the anterior chamber and the plasma and from aqueous flow rate based on a transfer equation formulating the kinetics of protein molecules in the anterior chamber. The k(in) showed a significant reduction at 3 and 4 hr after drug administration with a maximum decrease of 21 +/- 6% (mean +/- S.E., n = 10) at 3 hr, while the aqueous flow rate showed a significant reduction from 2 to 6 hr with a maximum decrease of 45 +/- 5% at 3 hr. The results indicated that topical apraclonidine reduced both blood-aqueous barrier permeability as well as aqueous flow rate in humans. This dual reduction may relate to the efficacy of this drug in suppressing the post-laser intraocular pressure rises in patients.     

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 Effect of Cataract Surgery on the Blood-Anueous Barrier

Orally-administered fluorescein was used as a quantitative test of the blood-aqueous barrier in a group of patients who had undergone cataract extraction and intraocular lens implantation in one eye. There was no statistically significant difference in the concentration of fluorescein in the anterior chamber between the aphakic or pseudophakic eye and the control eye of the total group of 46 patients. Eyes with an intracapsular cataract extraction with medallion suture implant lens, however, had a significantly lower concentration of fluorescein in the anterior chamber as compared to the control eye. This difference is probably due to loss of fluorescein into the vitreous by mixing and diffusion. In eyes with an intact posterior capsule, the time course of anterior chamber fluorescence in the aphakic eye is more comparable to that of the phakic eye. In such eyes the blood-aqueous barrier seems to remain normal long after cataract extraction and intraocular lens implantation.     

Low doses of pilocarpine do not significantly increase outflow facility in the cynomolgus monkey

Low doses (10(-9)-10(-6) M) of pilocarpine reportedly increase outflow facility in the organ-cultured human eye, suggesting a direct action on the trabecular meshwork. M3 muscarinic receptors have been found in both cultured human trabecular meshwork cells and tissue. We determined whether low pilo doses would increase outflow facility in the living monkey. The anterior chambers of both eyes of 17 pentobarbital anesthetized cynomolgus monkeys were cannulated and outflow facility measured bilaterally by 2-level constant pressure perfusion after an initial 2 ml exchange with Bárány's perfusand containing 24.5 microM phenylephrine (PE). Two subsequent exchanges were performed with one eye receiving Bárány's + PE + 10(-10)-10(-4) M pilocarpine and the contralateral eye receiving only Bárány's + PE. Outflow facility was measured for 35-40 min following each exchange. Accommodation and pupil diameter were measured before each exchange and approximately every 10 min during facility measurements. Outflow facility was significantly increased by 154 and 313% in eyes treated with 10(-5) M and 10(-4) M pilocarpine, respectively, related to contralateral controls. Accommodation and miosis also were induced only at 10(-5) M (accommodation, 3.3 +/- 1.6 diopters, NS; miosis, -4.1 +/- 0.5 mm, P < or = 0.001) and 10(-4) M (accommodation, 10.6 +/- 0.0 diopters, P < or = 0.02; miosis, -3.4 +/- 1.0 mm, P < or = 0.025) pilocarpine. We conclude that low anterior chamber doses of pilocarpine do not increase outflow facility in the living monkey as reported in the organ-cultured human eye, nor do they induce miosis or accommodation. All three parameters respond to pilocarpine at similar doses, and there is no functional evidence of a meaningful outflow facility-relevant pilocarpine effect on the trabecular meshwork at doses lower than those which affect the ciliary muscle.     

Demonstration of an anterior diffusional pathway for solutes in the normal human eye with high spatial resolution contrast-enhanced dynamic MR imaging

PURPOSE: The present studies were conducted to determine whether a diffusional pathway for solutes exists from the ciliary body stroma to the anterior chamber of the human eye. The existence of such a pathway has been demonstrated in rabbits and monkeys, but such a pathway in humans would necessitate a shift in the physiological paradigm of the blood-aqueous barrier. METHODS: Seven normal human volunteers (five men, two women; age range, 27 to 59 years) underwent nine dynamic T1-weighted, spin-echo MR imaging studies, using intravenous, gadolinium-based contrast agents. RESULTS: In all cases, signal intensity rose rapidly in the ciliary body. In all subjects, there was a measurable latent rise in signal strength (enhancement) in the anterior chamber. Signal enhancement typically occurred in the angle of the anterior chamber earlier, and to a greater degree, than within the center of the chamber. Increased signal within the posterior chamber was significantly less than in the anterior chamber, with measured increases probably attributable to volume averaging. CONCLUSIONS: These findings are consistent with the existence of an anterior diffusional pathway in the human eye. The model warrants further testing.     

Increased permeability of the blood-aqueous barrier after panretinal photocoagulation for proliferative diabetic retinopathy.

PURPOSE: To measure the permeability of the blood-aqueous barrier before and after panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy. METHODS: Twenty patients with diabetic proliferative retinopathy in one eye and background retinopathy in the other eye were included. PRP was performed in the proliferative eye, while the other eye served as control. Aqueous flare intensity was measured with a laser flare cell meter before, 10 and 90 days after treatment. RESULTS: The flare was stable in the control eye with a flare of 4.5+/-2.3, 4.4+/-2.4, and 4.5+/-1.7 photon counts/ms (mean+/-standard deviation) on Day 0, 10 and 90. In the laser treated eye corresponding figures were 5.2+/-2.4, 9.6+/-3.3, and 7.1+/-2.8 photon counts/ms, with a significant increase in aqueous flare at 10 days (p<0.001) and 90 days (p=0.002). CONCLUSION: A significant increase in aqueous flare was found 10 days after PRP, indicating a breakdown of the blood-aqueous barrier after retinal laser treatment. The breakdown was still present, however, less pronounced, after 3 months.     

Comparison of 0.1% dexamethasone phosphate eye gel (Dexagel) and 1% prednisolone acetate eye suspension in the treatment of post-operative inflammation after cataract surgery

A prospective, multi-centre, clinical parallel group study was conducted to assess the efficacy and safety of a new 0.1% dexamethasone phosphate eye gel (Group 1, n= 117) compared to 1% prednisolone acetate eye suspension (Group 2I, n=119) in a total of 236 patients (safety population), aged 39-92 years, following cataract surgery. Both drugs were given four times a day for 14 days starting 24+/-4 h after surgery. Criteria for evaluation were the reduction in anterior chamber flare and inflammation severity score (primary efficacy criteria) as well as different secondary efficacy and safety evaluation criteria. Laser photometry (LFM-500, Kowa), slit lamp assessment and the examination of other objective and subjective symptoms of ocular discomfort were performed between the last preoperative and 14th post-operative day. There were no statistically significant differences between the treatment groups concerning primary and secondary efficacy criteria. The mean reduction in anterior chamber flare from day 1 to day 14 post-operatively was 8.34+/-20.80 photons/ms with 0.1% dexamethasone eye gel and 5.72+/-16.70 photons/ms with 1% prednisolone eye suspension. The mean reduction of inflammation severity score was 1.8+/-1.3 points in Group 1 and 2.0+/-1.1 points in Group 2. Intra-ocular pressure did not increase after treatment with 0.1% dexamethasone phosphate eye gel. CONCLUSION: the results of the study underline the protective effect of topically applied 0.1% dexamethasone phosphate eye gel on the blood-aqueous barrier. This drug is an effective and safe steroidal antiinflammatory agent for topical use following cataract surgery and intraocular lens implantation.     

Effect of topical epinephrine on permeability of blood-aqueous barrier in human eyes.

The time-course of changes in the effects of topical epinephrine on the aqueous flow and the coefficient of protein entry into the anterior chamber (k(in)) were determined in 12 normal human subjects. Before and after instillation of 1.25% epinephrine in one eye, protein concentration in the anterior chamber (Ca) was determined from aqueous flare intensity using the laser flare-cell meter, and aqueous flow rate was determined by fluorophotometry. The k(in) was calculated from the Ca, plasma protein concentration, and aqueous flow rate. A single instillation of epinephrine affected neither the Ca nor the aqueous flow rate significantly. The calculated value of the k(in) showed no significant changes at any time of determination, which implied that a single instillation of epinephrine is insufficient to affect the permeability of the blood-aqueous barrier to plasma protein in the normal human eye.     

Repetitive instillation of 0.1% cyclosporin A eye drops induces miosis and anterior chamber inflammation-like reactions in monkey eyes

PURPOSE: Miosis and anterior chamber inflammation-like reactions were recognized after six instillations of 0.1% cyclosporin A eye drops every 30 minutes into rabbit conjunctival sacs. In order to consider species specificity, 0.1% cyclosporin A eye drops were applied by the same method in monkeys. METHODS: Eye drops were applied in five monkeys (monkey A, B, C, D, E); in one eye as control and in nine eyes with 0.1% cyclosporin A. We investigated the changes of pupil diameter, intraocular pressure, and anterior chamber flare before and after applying the eye drops. We also examined the effect on ocular tissue histopathologically. RESULTS: Miosis was recognized in six eyes, but no significant intraocular pressure change was observed in any eyes. In both eyes of monkey A anterior chamber flare increased significantly, and flare increased slightly in both eyes of monkeys B, C, and D. On the other hand, there was no change in either eye of monkey E, including the control eye. Localized necrosis of nonpigmented ciliary epithelium was recognized at the beginning of the ciliary process in both eyes of monkey A. Mild cystoid degeneration of nonpigmented ciliary epithelium was seen at the beginning of the ciliary process in the right eye of monkey C, and in the left eye of monkey D. CONCLUSION: No species specificity can be recognized in monkeys from the fact that there is the selective destruction of nonpigmented epithelium at the beginning of the ciliary process after repeated instillation of 0.1% cyclosporin A eye drops, although there was a difference in miosis and anterior chamber inflammation-like reaction in individual monkeys.