Angle closure glaucoma precipitated by aerosolized atropine.

Angle closure glaucoma is an infrequent form of glaucoma occurring when the filtration mechanism for the aqueous humor is obstructed by apposition of the peripheral iris to the trabecular meshwork. Anatomic features associated with acute-angle closure include congenitally small anterior segments, increased lens thickness, and shallow anterior chamber depth. We present two patients who developed signs and symptoms of angle closure glaucoma after receiving aerosolized atropine for treatment of chronic obstructive pulmonary disease. We recommend that before instituting therapy with an inhaled anticholinergic agent, the patient should be questioned concerning prior history of angle closure glaucoma symptoms and signs and the anterior chamber depth should be examined using iris illumination. Patients having shallow anterior chambers, or possible prior angle closure glaucoma attacks, should be examined by an ophthalmologist before inhalant anticholinergic therapy.

Monocular polyopia.

A patient with monocular polyopia underwent extensive neurologic investigation over a two-year period. Ocular examination disclosed a corneal degenerative change as the cause, and symptomatic relief was obtained with pilocarpine hydrochloride drops.

Immunohistochemical pathology of the corneal endothelium in iridocorneal endothelial syndrome.

PURPOSE: To evaluate immunohistochemical staining of the endothelia of corneas from patients with clinical diagnoses of iridocorneal endothelial (ICE) syndrome. METHODS: Corneas diagnosed with ICE syndrome and removed during corneal transplantation were freshly frozen, sectioned, and stained with monoclonal antibodies to keratin subgroups, vimentin, desmin, and a series of other antibodies against intermediate filaments. Transmission electron microscopy was performed on segments of these corneas fixed in glutaraldehyde. RESULTS: There was almost universal staining of the endothelial layer with A1 and A3 keratin monoclonal antibodies and vimentin. Transmission electron microscopy of the corneas also confirmed features consistent with keratin. CONCLUSIONS: The "endothelial" cell layer in the iridocorneal endothelial syndrome has electron microscopic and immunohistochemical characteristics of epithelial-like cells, but it also cross-reacts with vimentin, suggesting that these cells retain or derive some endothelial staining characteristics as well. This "epithelialization" of the endothelial layer may explain the progressive cellular proliferation across angle and iris similar to that seen in iatrogenic epithelial downgrowth and posterior polymorphous endothelial dystrophy.

Inhibition of conjunctival transdifferentiation by topical retinoids.

During the healing of a total corneal epithelial defect extending beyond the limbus, conjunctival transdifferentiation can be inhibited by corneal vascularization as evidenced by the lack of morphological transformation of the conjunctival epithelium into a cornea-like epithelium and the persistence of goblet cells on the corneal surface. We speculated that corneal vascularization might play a causative role in inhibiting conjunctival transdifferentiation, and examined the hypothesis that vitamin A or retinoids might be one of the blood-borne factors in modulating this process. To test this hypothesis, we created total corneal epithelial defects extending 3 mm beyond the limbus in rabbits using n-heptanol, and segregated the resultant corneas into nonvascularized and vascularized groups. After re-epithelialization, both groups received topical 0.1% Etretinate (Roche-Hoffmann, Nutley, NJ) or 13-cis retinoic acid in corn oil three times a day for 8 weeks. Controls received corn oil only. The extent of transdifferentiation was analyzed by assaying goblet cell density and distribution using flat-mount preparations and Alcian blue and periodic acid-Schiff stains (Fischer Scientific Co., Fair Lawn, NJ) and by conventional histology. Topical retinoid application inhibited conjunctival transdifferentiation in nonvascularized corneas to the same extent as that caused by corneal vascularization, suggesting that vitamin A is an important blood-borne factor for goblet cell maintenance. Its relative deficiency in the normal avascular cornea may explain why conjunctival transdifferentiation occurs.

Measurement of ultraviolet radiation at the surface of the eye.

PURPOSE: A new method for the measurement of ultraviolet radiation that reaches the surface of the eye is described. METHODS: The technique uses contact lenses produced from the ultraviolet-sensitive plastic polysulfone. Two types of polysulfone contact lenses (9 mm and 12 mm in diameter) were manufactured from a polysulfone rod. The 9-mm polysulfone contact lens could be calibrated and used to determine the ocular-to-ambient exposure ratio in a fashion similar to polysulfone film badges. The 12-mm polysulfone contact lens was designed as a "piggy-back" lens and required a larger diameter polymethlylmethacrylate carrier lens to fit the eye adequately. A method of in vivo stabilization was developed to minimize lens rotation. RESULTS: During four wearing trials, the ratio of ocular-to-ambient ultraviolet exposure ranged from 4% to 23%. CONCLUSIONS: Contact lenses manufactured from polysulfone offer the potential to study the exposure of the eye to ultraviolet radiation. The smaller diameter lens can measure an average ocular exposure, whereas the larger, stabilized, piggy-back design may allow regional dose assessment across the entire lens surface.

Posterior corneal rings in monkeys.

Contact wide-field specular microscopy was performed on 27 monkeys of known ages. The induction of posterior corneal rings as a result of applanation pressure to be age-dependent. There was a total absence of these folds in animals under two years of age, and they usually occurred only in animals older than four years of age.

Goblet cell density and vascularization during conjunctival transdifferentiation.

After debridement of the entire corneal epithelium with n-heptanol, two groups of rabbit corneas were segregated according to the extent of corneal neovascularization. Using a new topographic goblet-cell counting method and routine histology, the authors have reexamined the process of conjunctival transdifferentiation and compared the changes of goblet-cell density and morphology between nonvascularized and vascularized groups for a follow-up period of 167 days. Analysis of the total goblet-cell density disclosed that no goblet cells appeared on the corneal surface during the entire period of reepithelialization. After that, two phases were identified with respect to goblet-cell density: phase I (day 0-17) and phase II (after day 17). In phase I, both groups had a similar surge of goblet cells, with the peak occurring between days 7 and 11, suggesting little correlation with vascularization. Morphologic studies indicated the presence of a prominent centripetal cellular migration. In phase II, the nonvascularized group showed a rapid decline in goblet-cell density, and as a result the morphologic transdifferentiation into a cornea-like epithelium was completed on day 43. The changes of goblet cells to a smaller size and the presence of a more acidic mucin in the centrifugal receding zone, suggested that transdifferentiation on nonvascularized corneas is a process involving changes of cellular differentiation. In contrast, the vascularized group maintained a high plateau of goblet-cell density and an epithelium with conjunctival characteristics until day 167. This result disclosed that retardation of conjunctival transdifferentiation by corneal vascularization was in phase II. The possible role of vascularization in the modulation of conjunctival transdifferentiation is discussed.

Quantitative analysis of wide-field specular microscopy. II. Precision of sampling from the central corneal endothelium.

The precision of the measurement of mean endothelial cell area obtained by sampling with small-field and wide-field specular microscopy from the central 4 mm of human corneal endothelium was studied by comparing endothelial cell parameters from individual specular micrographs in vivo to the results obtained by montaging the micrographs from the entire central 4 mm of the same corneas. The small samples were at least 10% from the true mean cell size of all cells of the central 4 mm in any endothelium other than that with the most homogeneous pattern. A new algorithm for sampling with these two specular microscopes will need to be derived to permit a more precise measure of the mean area of endothelial cells in the central 4 mm of the human corneal endothelium.

Epithelial characteristics of the endothelium in Chandler's syndrome.

The cells lining the posterior surface of a corneal button obtained from a patient with Chandler's syndrome were examined by transmission and scanning electron microscopy, and by keratin staining. The ultrastructural appearance with intracytoplasmic 8 nm filaments, desmosomes, microvillous projections, and positive keratin staining suggests that these may be epithelial cells. Clinical specular microscopy of this cornea prior to transplantation revealed characteristic changes that were seen to be related to the density of microvillous projections on the cell membrane.

Corneal epithelial regeneration and adhesion following acid burns in the rhesus monkey.

For study of corneal adhesion after chemical injury, sulfuric acid was used to burn the central and peripheral corneal epithelium in rhesus monkeys. The adhesion properties of the regenerating epithelium were sequentially followed by clinical assessment and by serial corneal biopsy specimens examined by transmission electron microscopy. The peripheral burns healed uneventfully, but the central corneal burns resulted in persistently loose adhesion for more than 8 weeks. The pathogenesis of the defective epithelial adhesion appeared to initially the persistence of the original basement membrane that could not be utilized by regenerating epithelium. Later, poor adhesion was related to the slow rate of basement membrane regeneration and also to fragmentation of the Bowman's layer substrate and to mild stromal edema.

Incidence of ocular surface epithelial dysplasia in metropolitan Brisbane. A 10-year survey.

The ocular histologic records of all hospital and private pathologic laboratories in metropolitan Brisbane, Australia, were surveyed from 1980 through 1989. One hundred thirty-nine cases of histologically proven dysplasia, carcinoma in situ, and invasive carcinoma of the cornea and conjunctiva were identified. The incidence of these conditions in the area surveyed is estimated to be 1.9 per 100,000 per year averaged for 10 years.

Clinical specular microscopy of corneal endothelial rejection.

Clinical specular microscopy was performed during acute rejection episodes in 20 patients. The following five distinct morphologic changes were noted: (1) "blackout" areas due to deposition of wandering cells on the endothelial layer, (2) intracytoplasmic blackout areas of unknown cause, (3) intracellular "bright" oval bodies related to the cell nucleus, (4) prominent variation in cell size, and (5) a sharp demarcation line of affected endothelial cells in a linear-type rejection. These morphologic changes were severe even in early rejection, and there was frequent persistence after the rejection episode was considered controlled by slit-lamp examination. Although these changes were not pathognomonic for endothelial rejection and could be seen in isolation in idiopathic uveitis and normal corneal transplant endothelium, a constellation of all these changes appeared specific for endothelial rejection.

Corneal blood staining at low pressures.

After sustaining blunt ocular trauma and total hyphemas, two patients quickly developed corneal blood staining in the absence of elevated intraocular pressure. Corneal blood staining has previously been reported to occur in association with hyphema and raised intraocular pressures. Although several bibliographic references acknowledge that corneal blood staining may occur without raised pressure, a careful review of the literature failed to reveal any well-documented cases.

Invasive squamous cell carcinoma of the conjunctiva.

A 73-year-old man had been treated for a sore, red, left eye for 4 months before a clinical diagnosis of squamous cell carcinoma of the limbus was made. This diagnosis was confirmed on examination of a biopsy specimen, but after an initial surgical attempt to fully excise the tumor, there was clinical evidence of intraocular spread. An extensive corneoscleral resection and iridocyclectomy appeared to completely excise the tumor, as indicated by frozen section review. However, 1 year later, the patient re-presented with obvious residual squamous cell carcinoma of the iris and trabecular meshwork, well away from the original tumor site. Subsequent exenteration has resulted in a tumor-free patient for 1 year. Apparent surgical clearance of an extensive squamous cell carcinoma does not ensure total intraocular clearance of residual tumor, which may be remote from the original tumor site.

The eye in bone marrow transplantation. I. Clinical study.

A prospective study of 45 patients undergoing bone marrow transplantation included full ocular examination and pretransplant and posttransplant conjunctival biopsies. The major finding was the development of a severe keratoconjunctivitis sicca syndrome that developed in 20 of the 45 patients and closely correlated with the occurrence of acute graft-v-host disease (GVHD). An acute pseudomembranous conjunctivitis in the fulminant stage of acute GVHD developed in six patients. A further ten patients made up a retrospective assessment of bone marrow transplantation and confirmed these clinical findings.

Comparative studies of corneal surface injury in the monkey and rabbit.

This animal study of corneal surface injury using acid, alkali n-heptanol, iodine, keratectomy, or scraping, despite morphologic differences from the human, simulated the human response to these forms of trauma. The rabbit and monkey thus remain useful models for the study of the effects of chemical and physical injury on the corneal surface. Although abnormalities in the basement membrane complex seem to play an important role in corneal epithelial adhesion problems, the presence of a poor substratum on which adhesion complexes must in turn rely for their stromal attachment is also an important factor.

Amodiaquine ocular changes.

A 34-year-old man ingested more then 250 g of amodiaquine hydrochloride (for pain) during one year and was noted to have diffuse conjunctival, corneal, and skin changes and also abnormal results from retinal function tests. Ultrastructural examination of corneal and conjunctival biopsy specimens revealed intralysosomal membranous and amorphous inclusions in corneal epithelial cells, conjunctival epithelial cells, keratocytes, and vascular endothelial cells. Follow-up of more than two years and repeated conjunctival biopsy specimens revealed diminution in both the clinical and electron microscopic abnormalities, but persistence in abnormal results of retinal function tests. These changes are consistent with a drug-induced phospholipidosis.

Posterior corneal pigmentation and fibrous proliferation by iris melanocytes.

Pigmentation of the posterior corneal surface results either from endothelial phagocytosis of free melanin pigment or from the presence of iris melanocytes, iris pigment epithelial cells, or pigment-containing macrophages on the posterior corneal surface. Although this is occasionally seen clinically, it is more often noted at histopathologic evaluation after operative or accidental ocular trauma. Three cases of posterior corneal pigmentation by iris melanocytes are reported. In one case, the pigmented membrane was the major cause of considerable visual impairment and was documented with clinical photographs and specular microscopy. By light and electron microscopy, all three cases were consistent with findings of posterior corneal pigmentation by iris stromal melanocytes that had acquired endothelium-like morphologic characteristics. We also consider the possible contribution of these melanocytes to posterior collagen layers of the cornea.

The eye in bone marrow transplantation. II. Histopathology.

The major histopathologic changes seen in the eyes of patients undergoing bone marrow transplantation involve the conjunctiva, cornea, choroid, and lacrimal gland. The major finding in the conjunctiva is keratinization. The major findings in the cornea are epithelial thinning and keratinization. Keratinization of the conjunctiva and cornea is associated with graft-v-host disease (GVHD) and may be either a primary manifestation of GVHD or be secondary to the "dry eye" syndrome that develops in patients with GVHD. Corneal epithelial thinning is probably secondary to the chemotherapy used in the preparative regimen. An unusual histiocytelike infiltrate is present in the choroid and appears to be associated with GVHD. In acute GVHD, lacrimal gland stasis occurs and is the probable cause of the dry eyes seen in these patients.

Ocular surface squamous neoplasia.

Ocular surface squamous neoplasia presents as a spectrum from simple dysplasia to carcinoma in situ to invasive squamous cell carcinoma involving the conjunctiva as well as the cornea. It is a distinct clinical entity, although it has been known by a variety of different names throughout the literature. Most commonly it arises in the limbal region, occurring particularly in elderly males who have lived in geographic areas exposed to high levels of ultraviolet-B radiation. Symptoms range from none to severe pain and visual loss. The development of preoperative diagnostic techniques, such as impression cytology, are of value in clinical decision making and follow-up management. Simple excision with adequate margins is currently the best established form of treatment despite trials of other modalities. The course of this disease may be evanescent, but is more frequently slowly progressive and may require exenteration and occasionally may lead to death.