Ultrastructural changes in the trabecular meshwork of human eyes treated with corticosteroids.

OBJECTIVES: To study the ultrastructure of the trabecular meshwork in human eyes with corticosteroid-induced glaucoma and to determine whether the changes noted also occur in the eyes of patients with primary open-angle glaucoma (POAG) who have been treated with corticosteroids. METHODS: The trabecular meshwork from 5 patients in whom corticosteroid-induced glaucoma was diagnosed and from 6 patients with POAG who had been treated with systemic or topical corticosteroids for months to years was investigated with light and electron microscopy. None of the eyes with POAG were considered to have corticosteroid-induced elevation of the intraocular pressure. RESULTS: Eyes with corticosteroid-induced glaucoma had the accumulation of extracellular material distinct from the sheath-derived plaques typical of POAG. A finger-printlike arranged material resembling basement membranes (FBM material), considered characteristic of corticosteroid-induced glaucoma, was found in all eyes with corticosteroid-induced glaucoma. In addition, an abnormal accumulation of densely packed, fine fibrils immediately beneath the inner wall endothelium of Schlemm's canal was present. The findings were similar among patients receiving topical or systemic treatment and among patients of different ages. In the eyes from donors with POAG who had been treated with corticosteroids, the fine fibrillar material and FBM material were present in small amounts in 3 of 6 donors and were not found in the other 3 donors. CONCLUSIONS: The extracellular material that accumulates in eyes with corticosteroid-induced glaucoma differs from that seen in eyes with POAG. Eyes with POAG exposed to long-term corticosteroid treatment did not all respond with the formation of the abnormal extracellular materials characteristic of those found in eyes with corticosteroid-induced glaucoma.

Ultrastructural changes in the trabecular meshwork of juvenile glaucoma.

Trabeculectomy specimens from 11 patients with juvenile glaucoma were studied by electron microscopy and quantitatively evaluated. In all cases, large amounts of extracellular material arranged in a fingerprint-like pattern, resembling basement-membrane-like material (FBM) was found, similar to that described in steroid-induced glaucoma. This material was found mainly within the inner cribriform and outer corneoscleral regions of the trabecular meshwork, and caused the cribriform layer to be greatly thickened. FBM was also intimately associated with trabecular cells, which frequently appeared activated. In 3 cases, there was also an increase in fine fibrillar material which resembled that found in eyes with steroid-induced glaucoma. The amount of sheath-derived plaque material, which is increased in primary open angle glaucoma, was greatly increased in the subendothelial layer adjacent to Schlemm's canal.

Dorzolamide, a topical carbonic anhydrase inhibitor: a two-week dose-response study in patients with glaucoma or ocular hypertension.

We investigated the dose-response relationship of the intraocular pressure-lowering activity of dorzolamide, a novel topical carbonic anhydrase inhibitor previously known as MK-507. A double-masked, randomized, multicenter study of 113 patients with either primary open-angle glaucoma or ocular hypertension was conducted; dorzolamide (0.2, 0.5, 1, or 2%) was administered three times daily for 14 days. All of the dorzolamide concentrations substantially lowered intraocular pressure from baseline measurements. The percentage change in baseline intraocular pressure with 0.5, 1, and 2% dorzolamide 2, 4, and 6 h after dosing on day 14 ranged from 12.0 to 17.0% on average, which was greater than after treatment with 0.2% dorzolamide. No dose response was seen for 0.5, 1, or 2% dorzolamide. The most frequently reported ocular symptom was transient smarting, which occurred in 35.6-74.1% of every treatment group. Smarting and mild hyperemia were most frequent with 2% dorzolamide (74.1 and 18.5%, respectively). The present results indicate that the 0.5, 1, and 2% concentrations of dorzolamide are almost equally effective and that 2% concentrations may be less well-tolerated than 0.5 or 1% concentrations.

Clinical features of capsular glaucoma in comparison with primary open-angle glaucoma in Japan.

Clinical features of capsular glaucoma during a recent 15-year period were compared with those of primary open-angle glaucoma (POAG). Out of 1623 new glaucoma patients, 263 patients (16.2%) were capsular glaucoma and 268 (16.5%) were POAG. The patients with capsular glaucoma were older than the patients with POAG. The former had higher intraocular pressure, lower visual acuity, more advanced visual field change and heavier trabecular pigmentation than POAG patients at the time of initial examination. These findings suggest that capsular glaucoma is more difficult to manage than POAG and that the prognosis is poorer than for POAG. Pseudoexfoliative material was found on the pupillary border in 98.3%, on the central lens surface in 46.1%, and on the peripheral lens surface in 72.3%. Though 190 of 263 patients with capsular glaucoma (73.9%) were unilateral cases, 38.9% of the fellow eyes had some abnormalities related to glaucoma. Phakodonesis was found in 10% of patients with capsular glaucoma. This finding suggests that the presence of capsular glaucoma might be a risk factor in cataract surgery.

Epidemiology of glaucoma in Japan--a nationwide glaucoma survey.

A population-based, collaborative glaucoma survey was conducted in seven regions throughout Japan, during the years of 1988 and 1989. The total number of subjects examined was 8,126 out of 16,078 residents aged 40 years or older, representing a participation rate of 50.54%. There were no significant differences in background factors between participants and randomly sampled nonparticipants. A mainstay of the screening consisted of tonometry and fundus photography with nonmydriatic camera, followed by automatic perimetry as a recall examination. Overall prevalences obtained were primary open-angle glaucoma (POAG) 0.58%, low-tension glaucoma (LTG) 2.04%, primary angle closure glaucoma (PACG) 0.34%, other types of glaucomas 0.60%, and ocular hypertension (OH) 1.37% at the time of screening. The very high prevalence of LTG and extremely low prevalence of OH in the Japanese might reflect a racial peculiarity in the age-specific trend of the intraocular pressure. The prevalence of PACG was found much higher in Japanese than in Caucasians, with a predilection for women. Racial peculiarities as revealed in this study were discussed, with particular reference to the refractive status in the Japanese that showed progressive decrease in myopia with age.

Phakodonesis in capsular glaucoma: a clinical and electron microscopic study.

Subluxation of the lens and phakodonesis were found in 22 out of 261 patients with capsular glaucoma. The overall incidence of these conditions was 8.4%. Electron microscopic examinations demonstrated that the zonular fibers of the lens with phakodonesis had marked degenerative changes, while in the lens without phakodonesis the zonular fibers were nearly normal in appearance. At the present time when the main cataract extraction procedure has been changed from ICCE to either ECCE or ECCE plus IOL implantation, phakodonesis must be considered as a sign of high risk concerning the prognosis of the operation. Phakodonesis should be taken into account when planning an operation on an eye containing pseudoexfoliative material.

The fine structure of pigment epithelium of the iris in capsular glaucoma.

An electron microscopic study was performed on the pigment epithelium of the iris in 13 patients with capsular glaucoma. Pseudoexfoliative material (PE) was often observed in small depressions or indentations of the cell membrane of the posterior pigment epithelium. PE was also found in the region where the cell membrane was indistinct and took a course perpendicular to the surface of the cell membrane. Serial sections revealed no PE in the cytoplasm of the posterior pigment epithelium. Furthermore, the PE found extracellularly was continuous with the cell membrane. Three stages were distinguished in the pigment epithelium as capsular glaucoma progressed. At an early stage (stage 1), the number of infoldings in the posterior pigment epithelium increased, and PE was found at that site. In a more advanced stage (stage 2), the cytoplasmic processes increased in number and the basement membrane became discontinuous. In a further advanced stage (stage 3), a large amount of PE was found in the posterior chamber. The intercellular space between two adjacent pigment epithelial cells increased and the cytoplasmic processes gradually disintegrated. Only one significant correlation was found between the glaucoma stage and the stage of changes in the pigment epithelium. No associations were found between the stage of changes in the pigment epithelium and patient age or gonioscopic findings.

Familial amyloidotic polyneuropathy: ocular manifestations with clinicopathological observation.

Clinical findings of ocular involvement in two patients with familial amyloidotic polyneuropathy are described. Both cases revealed irregular pupillary margin, white membranous material on the pupillary border and on the lens surface. Open-angle glaucoma was found in one case, and ocular hypertension in the other. Histopathological examination of the tissues obtained during trabeculectomy in Case 1 revealed a large amount of amyloid substance around the vessels of the conjunctiva and the iris and in the endothelial meshwork of the chamber angle. Electron microscopic observation revealed that amyloid fibrils had formed in the basement membrane of the endothelial cells of the blood vessels in the conjunctiva and the iris. However, no amyloid fibrils were observed in the endothelial cells of the trabecular meshwork. Crossed immunoelectrophoresis of the aqueous humor of Case 1 showed a high-protein content, especially of alpha 1-lipoprotein and ceruloplasmin. The findings described above suggest that glaucoma or ocular hypertension in association with familial amyloidotic polyneuropathy is a result of the accumulation of amyloid substance in the endothelial meshwork.

Ultrahistochemical studies on tangential sections of the trabecular meshwork in normal and glaucomatous eyes.

The composition of the extracellular material of the cribriform meshwork was compared in five normal and 13 glaucomatous eyes of the same age group (58 to 70 years). Enzymatic digestion and histochemical methods applicable to electron microscopy were used. In both groups of eyes the ground substance was sensitive to chondroitinase ABC, and also the other methods showed no qualitative differences between the groups. In contrast, the fibrillar components of the extracellular material, which partly could be studied only after enzymatic treatment, showed qualitative differences between normal and glaucomatous eyes. In addition to the normal fibrous components, the glaucoma tissue contained large amounts of very fine fibrils. In seven eyes with end-stage glaucoma these fibrils filled the whole cribriform region. In these cases collagen fibers also appeared. Whether these were formed from the fine fibrils is not clear.

The fine structure of the cribriform meshwork in normal and glaucomatous eyes as seen in tangential sections.

Electron microscopic serial sections in a tangential plane through the inner wall of Schlemm's canal and the trabecular meshwork in normal and glaucomatous eyes revealed a characteristic network of elastic-like fibers (cribriform plexus), which is directly connected to the inner wall endothelium by a special fiber system (connecting fibrils). This cribriform plexus is also connected to the ciliary muscle system. Ciliary muscle tendons were found that not only show the same fine structure as the cribriform plexus but also join it. The ciliary muscle tone can therefore directly influence the fiber system of the cribriform plexus and its connections to the inner wall of Schlemm's canal. in eyes with chronic simple glaucoma, three types of plaques in the cribriform meshwork have been described after studies of sagittal sections. A comparison with tangential sections of the same piece of tissue shows that plaques of type II and III are in fact sections through the cribriform plexus and that only type I plaques are a separate entity.

Fine structure of trabecular meshwork and iris in pigmentary glaucoma.

Trabecular meshwork and iris were studied by light and electron microscopy in a 40-year-old female with pigmentary glaucoma. Elevation of the intraocular pressure was most likely due to closure the intertrabecular space by pigment granules and large cells resembling clump cells, fibrous substances, and hypertrophied endothelial cells of the trabecular sheet, which had phagocytized pigment granules.