[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.

[Cellular characteristics of cultured non-pigmented ciliary epithelium from adult pigs].

PURPOSE: To compare the reactive proliferation of non-pigmented ciliary epithelial cells in patients with cyclitis, or after cyclophotocoagulation and cyclocryocoagulation, and the cultured non-pigmented ciliary epithelial cells from adult pigs. METHODS: Porcine ciliary epithelial cells were cultured and non-pigmented ciliary epithelial cells were isolated. Detection of DNA synthesis, morphological observation by a phase contrast microscope and a transmission electron microscope, and staining of senescence-associated beta-galactosidase were carried out. RESULTS: The cells proliferated without showing contact inhibition of growth or reconstitution of epithelial morphology. With a decrease of proliferative activity, the cultured cells expressed senescence-associated beta-galactosidase. Although DNA synthesis persisted for a long time, some cells in later culture periods showed morphologically abnormal nuclei or plural nuclei indicating dysfunction of cell division, or apoptotic features. CONCLUSION: The uncontrolled growth and loss of the epithelial nature of non-pigmented ciliary epithelial cells in vitro resembles the process of formation of cyclitic membrane and proliferation of ciliary epithelium after cyclophotocoagulation and cyclocryocoagulation in patients. Observatin of the behavior of cultured non-pigment epithelial cells could aid in understanding the mechanism of cyclitic membrane formation.

Autoantibody against neuron-specific enolase found in glaucoma patients causes retinal dysfunction in vivo.

PURPOSE: In our recent paper, we have reported the presence of serum autoantibody against neuron-specific enolase (NSE) in patients with glaucoma. The purpose of the present study was to investigate further the pathological effects of anti-NSE antibody on retina by comparing them with the effects induced by N-methyl-D-aspartate (NMDA). METHODS: Either a glaucoma patient's serum or purified anti-NSE antibody, or 10-40 mM NMDA was intravitreously administered into Lewis rat eyes, and electrophysiological, histopathological, and biochemical evaluations were performed. In addition, the neuroprotective effects of anti-glaucoma drugs, such as timolol, betaxolol, nipradilol, and isopropyl unoprostone, and a calcium antagonist were also studied using these animal models. RESULTS: Electron microscopy revealed that intravitreal administration of a glaucoma patient's serum, which immunoreacted with retinal 50 kDa in Western blot analysis, and purified anti-NSE antibody induced retinal ganglion cell apoptosis in rat eyes. Functionally, these eyes showed a significant decrease in electroretinogram (ERG) responses and a remarkable decrease in rhodopsin phosphorylation reaction. These changes were comparable to the effects observed after the intravitreal administration of 20 mM NMDA. Co-administration of nipradilol, an alpha- and beta-blocker, with anti-NSE antibody or 20 mM NMDA caused marked recovery of the affected ERG responses within 2 weeks. In contrast, administration of timolol or betaxolol showed no recovery effect on the ERG responses. Among these drugs, only betaxolol showed a recovery effect on NMDA-induced decrease of rhodopsin phosphorylation. Nilvadipine functioned beneficially on both impaired ERG and rhodopsin phosphorylation reactions observed in rat eyes injected intravitreously with anti-NSE antibody or NMDA. These effects of nilvadipine were not changed by the addition of endothelin-1. In contrast, isopropyl unoprostone had no effect on these functions. CONCLUSION: These observations suggest that serum autoantibody against NSE found in some patients with glaucoma induces retinal dysfunction in vivo, similarly to NMDA.

Statistical analysis of visual prognosis following stellate ganglion block treatment on patients with retinal vessel obstruction.

The visual outcome in 308 patients treated for retinal vessel obstruction was examined retrospectively and the effectiveness of each treatment was evaluated using stepwise multiple linear regression analysis and the chi-square test. Visual acuity was used as the parameter for assessing treatment effectiveness and the variables investigated included treatment factors [stellate ganglion block (SGB), urokinase administration, and prostaglandin administration] and patient factors (age, duration of visual impairment before treatment, hypertension, and diabetes mellitus). SGB treatment, the duration of visual impairment, and the presence of diabetes mellitus were significantly correlated with the visual prognosis following treatment. These results support the current hypothesis that SGB is a viable treatment for patients with obstructive disease of the retinal vessels.

[A case of primary congenital glaucoma with unilateral corneal amyloidosis].

BACKGROUND: Histopathological evaluation of primary congenital glaucoma with extensive corneal amyloidosis. CLINICAL FINDINGS: A three-month-old infant. At the first examination, corneal diameter was 12 mm in both eyes, intraocular pressure (IOP) 43 mmHg in the right eye and 47 mmHg in the left eye. A diagnosis was made of primary congenital glaucoma. At 4 months of age bilateral goniotomy, at 1 year and 2 months of age bilateral goniotomy, and at 2 years and 2 months of age bilateral trabeculectomy and the superficial keratectomy of the right eye were done. At 14 years and 11 months of age the enucleation of the right eye was done because of corneal opacity, visual loss, and figure. HISTOPATHOLOGICAL FINDINGS: In the cornea disappearance of Bowman's membrane, accumulation of amyloid in the rough endoplasmic reticulum of the basal cells and subepithelial fibroblasts, and thickeniny of Descemet's membrane could be seen. At the peripheral anterior synechia new Descemet's membrane was spread over the anterior surface of the peripheral iris. CONCLUSION: Unilateral corneal amyloidosis might have been present in infancy, amyloid produced in the rough endoplasmic reticulum of the basal epithelium and subepithelial fibroblasts and deposited in the subepithelial region. At puberty amyloid might have been produced in the subepithelial fibroblasts. The poor IOP control at puberty might have been due to the complication of neovascular glaucoma.

[Histopathologic study on cyclocryotherapy of human and monkey eyes].

PURPOSE: To evaluate the lesion and repair process of the ciliary body and adjacent tissues in glaucomatous human eyes and normal monkey eyes with cyclocryotherapy. METHODS: We used light and electron microscopy to observe the ciliary body and adjacent tissues in five glaucomatous human eyes and five normal monkey eyes which were given cyclocryotherapy. RESULTS: Five absolute glaucomatous eyes were given cyclocryotherapy from one and a half to 3 years before the enucleation. One eye had no coagulated spots on the ciliary process, but five eyes had coagulated spots on the pars plana. The pigment epithelial cells were atrophic or had disappeared, but non-pigment epithelial cells had proliferated by one or two layers. At the lesion of monkey pars plicata cyclocryotherapy up to three months, melanophage phagocytosed pigment epithelium and melanocytes accumulated, although the proliferation of non-pigment epithelial cells was seen. At the lesion of monkey pars plana cyclocryotherapy melanophage accumulation was also marked, although non-pigment epithelial proliferation was greater than in pars plicata cyclocryotherapy. CONCLUSION: As cyclocryotherapy is a blind therapy, it is uncertain and difficult to destroy the ciliary process precisely. The repair process continued up to three months after monkey cyclocryotherapy, but it took up to one year and 6 months after human cyclocryotherapy.

[Electrophysiological and histopathological study on visual toxicity of clioquinol].

OBJECTIVE: To evaluate the effect of clioquinol on the optic nerve and retina of rhesus monkeys by ophthalmoscopy, electrophysiology and histopathology. METHODS: Clioquinol was given orally to 5 monkeys, gradually increasingly from 100 mg/kg/day up to 14 months(total dosage 227 g/kg). Ophthalmoscopy, erectroretinogram(ERG), visual evoked potential(VEP) and histopathological examination of enucleated eyeballs were done periodically up to 10 years. RESULTS: The margin of the optic disc was not clear at the early stage, but the colour became atrophic at the late stage. VEP maximum amplitude decreased quickly at the early stage and the amplitude of ERG a and b waves and oscillatory potential decreased gradually. 37 months after the discontinuation of administration of VEP, ERG amplitude increased gradually. Swelling of axons and disorganization of the myelin sheath were noticed 2.5 months after beginning treatment. Swelling of the peripapillary nerve fiber layer was seen 5.5 months after beginning treatment. Karyorrhexis was seen in the inner layer of the retina after 12.5 months. Axonal swelling disappeared and the myelin sheath became reorganized 9 months after the discontinuation of treatment. CONCLUSIONS: Clioquinol produced an early decrease of electrophysiological function, but recovery of function was seen after discontinuation of treatment. The degeneration of axons and myelin sheath continued during treatment, and interruption of the degeneration was seen after discontinuation of treatment.

Hypotensive effect of latanoprost/timolol versus travoprost/timolol fixed combinations in NTG patients: a randomized, multicenter, crossover clinical trial.

PURPOSE: To compare the ocular hypotensive effect of travoprost plus timolol (TTFC) and latanoprost plus timolol fixed combinations (LTFC) in patients with normal-tension glaucoma (NTG). METHODS: A two-sequence 12-week, multicenter, prospective, randomized, single-blinded, crossover clinical trial examined 59 NTG patients. If both eyes were eligible, only one eye (chosen at random) was used for analytical purposes. After a 12-week run-in period with dorzolamide plus timolol fixed combination (DTFC), patients were randomized into one of the two crossover sequences of treatment for 12 weeks with TTFC or LTFC and were subsequently crossed over to the alternative treatment for a further 12 weeks. The primary endpoint was reduction in IOP after 12 weeks of each treatment sequence. The effect of treatment on IOP was assessed using a linear mixed model. RESULTS: The mean baseline IOP was 14.8 ± 3.3 mm Hg (95% confidence interval [CI], 14.1-15.3 mm Hg) for treatment with DTFC. The TTFC treatment period showed consistently lower mean IOP compared with LTFC treatment period at all measurement time points. Mean reduction in IOP at 12 weeks was significantly greater in the TTFC group than in the LTFC group (-2.4 ± 2.3 mm Hg vs. -1.1 ± 2.3 mm Hg; P = 0.021). No interaction between the drug and treatment sequence was detected. The effects of intraocular lens implantation and measurement time were also not significant. The tolerability profiles of both treatments were similar. CONCLUSIONS: The additional reduction in IOP was greater with TTFC than with LTFC, and their tolerability profiles were similar. (http://www.umin.ac.jp/ctr/ number, UMIN 000005974.).