Ocular rigidity in keratoconus.
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Biomedical subjects
Publications and source records attributed to C S Foster.
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Four patients with symptomatic superior limbic keratoconjunctivitis underwent resection of the superior bulbar conjunctiva. One of these patients also underwent a tarsal conjunctival resection in the other eye. Three of the patients had previously been treated by various regimens without resolution; the fourth had had no prior treatment. All four patients had immediate and continued relief of the ocular symptoms after the superior bulbar conjunctiva was excised. The patient who underwent tarsal conjunctival resection experienced only short-term relief. We studied the conjunctival tissue by light and transmission electron microscopy. Both techniques revealed abnormalities related to the bulbar conjunctival surface with keratinization of the epithelium, acanthosis, degeneration of the nuclei, and intracellular accumulation of glycogen. Inflammatory cells were minimally present. The tarsal conjunctiva appeared essentially normal.
A patient with chronic unilateral conjunctivitis of six years' duration was discovered to have sebaceous carcinoma of the eyelid. This case is in many respects typical of the delay between onset and diagnosis frequently seen in this disease. Our case is unique, however, because it demonstrates that if not specifically alerted to the possibility of malignancy, even the experienced ophthalmic pathologist may misdiagnose. The factors necessary for early diagnosis of this disease are: (1) suspicion on the part of the clinician, (2) adequate surgical biopsies, and (3) examination of the biopsy specimen by an experienced pathologist who has been alerted to look for malignant changes.
A prominent histological feature of superior limbic keratoconjunctivitis is the presence of keratinization of the superior bulbar conjunctiva. Ultrastructurally the affected conjunctival epithelium shows all of the characteristics of keratinization as described in skin. There is a superficial layer of horny cells with reduced organelles and thickened cell membrane. In the intermediate layers, the cells contain an increased number of cytoplasmic filaments which are sometimes aggregated into dense masses, keratohyalin granules, both in the cytoplasm and in the nucleus, membrane coating granules, lysosomes and various other types of membranous structures.
A most unusual complication of penetrating keratoplasty is the rapid thermal denaturation of a human donor cornea upon accidental exposure to temperature of 50 degrees to 60 degrees C, the result of inadequate cooling of a Teflon trephine block following autoclave sterilization.
The examination of reducible collagen crosslinks in keratoconus cornea revealed the presence of lysinonorleucine in amounts far greater than in normal age-matched corneas. There was no indication of decreased hydroxylysine levels in keratoconus, and there were no clinical indications of a generalized connective tissue disorder. The abnormal levels of dehydrolysinonorleucine in the tissue may represent a change in hydroxylation of selected lysyl residues of normal collagen or the synthesis of abnormal collagen, perhaps an unusual type.
Superior limbic keratoconjunctivitis (SLK) is a condition of unknown etiology. Histological signs include acanthosis, dyskeratosis, keratinization, and ballon degeneration of the bulbar conjunctival epithelium. Ultrastructural examination of biopsy material from five eyes of patients with SLK shows numerous nuclear changes in the conjunctival epithelial cells. These include abnormal distribution and aggregation of nuclear chromatin, the presence of filaments within the nucleus, and dense accumulations of cytoplasmic filaments which surround the nucleus, resulting in "strangulation" and the formation of multilobed nuclei or multinucleated cells. These changes do not appear to have been described previously in any cell type.
Masked, controlled rabbit studies were done to determine the toxic effects on corneal wound healing of 0.1 percent idoxuridine drops, 3 percent adenine arabinoside monophosphate drops, and 1 percent trifluorothymidine drops, the clinically used concentrations. Neither idoxuridine nor trifluorothymidine significantly retarded closure of epithelial wounds. All three drugs caused toxic changes in the regenerating epithelium clinically and by histopathologic examination. Treatment with arabinoside monophosphate, the monophosphate ester of vidarabine, significantly retarded closure of epithelial wounds and caused impressive toxic changes in the regenerating epithelium. Vascularization of the corneal stroma was present in all eyes treated with this drug. The trifluorothymidine and idoxuridine had much milder toxic effects on regenerating epithelium and appeared equal in regard to production of such effects. The strength of stromal wounds was somewhat reduced by idoxuridine and trifluorothymidine and significantly increased by arabinoside monophosphate when compared to controls, These findings were confirmed by hydroxyproline assay of the stromal scars.
In a coded study, we treated 40 patients who had active herpes simplex corneal ulcers with either 1% trifluorothymidine (F3T) or 0.1% idoxuridine (IDU) drops; we treated 15 similarly afflicted patients, who had failed on IDU or vidarabine, with open 1% F3T drops. All dosages were at therapeutically recommended frequency. In the coded study there was no statistically significant difference between the drugs in rate of healing; mean initial ulcer size in both groups was approximately 7 mm2 and mean healing time was approximately 5.5 days. There was a significant difference, however, in the chances of successful healing; 96% of all F3T treated eyes and only 75% of IDU treated eyes healed completely within 14 days. In the open study, 87% of patients healed completely on F3T eyedrops. Although an insufficient number of patients were on concomitant coricosteroid therapy to provide statistical analysis, F3T-corticosteroid treated eyes (eight masked and open) all healed. The one IDU-corticosteroid treated eye in the masked study failed to heal.
It has been suggested that corticosteroids plus the effective antibiotics are more beneficial than antibiotics alone in reducing inflammation in infectious keratitis. Topical and subconjunctival corticosteroids as adjuncts to gentamicin therapy were evaluated by microbiological assay and clinical parameters in experimentally induced Pseudomonas keratitis in rabbits. Various strengths of dexamethasone given concurrently or delayed in conjunction with gentamicin therapy were studied. There was no statistically significant difference between combinations and the antibiotics alone in this experimental model.
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In vivo 31P magnetic resonance spectroscopy (MRS) was undertaken in 28 healthy adult individuals and 32 patients with hepatic malignancies of varying histology, using chemical shift imaging techniques. The mean peak area ratio (total range) of phosphomonoester (PME) to phosphodiester (PDE) in the health adult group was 0.23 (0.15-0.41). The mean (total range) PME/PDE ratio of the total patient group was 0.68 (0.15-2.38), which was significantly elevated (P less than 0.001) compared to the mean of the healthy adult group. Liver biopsies, obtained at operation, were analysed using high-field in vitro MRS techniques in order to identify the contributions of aqueous-soluble metabolites to the multicomponent PME and PDE in vivo signals. Concentrations of phosphorylethanolamine (PE), phosphorylcholine (PC), glycerophosphorylethanolamine (GPE) and glycerophosphorylcholine (GPC) were measured. The in vitro spectrum of six samples of liver of normal histological appearance all showed a similar pattern of PE, PC, GPE and GPC. The in vitro spectrum of seven liver tumours of differing histology all showed an increase in PE and PC signals and a decrease in GPC and GPE signals. The in vitro results were compared with in vivo findings in five patients. The increase in PME/PDE observed in vivo represented, in part, an increase in PE and PC in the PME region and a decrease in GPE and GPC in the PDE region.
To diagnose the cause of chronic unilateral external ocular inflammation, the physician must take into account many factors usually not considered in bilateral cases. We report on the diagnosis and treatment of ten unilateral cases encompassing a variety of ocular and systemic problems. The purpose of this report is to emphasize the importance of systematic consideration of all diagnostic possibilities and to suggest a diagnostic protocol to aid in the study of patients with chronic unilateral external ocular inflammation.
Advances in immunology, particularly ocular immunology, have been accompanied by the emergence of safer, more specific immunosuppressive drugs, notably, cyclophosphamide, chlorambucil, methotrexate, azathioprine, cyclosporine A, bromocriptine, dapsone, and colchicine. These drugs have become an important, and often essential, part of the ophthalmologist's armamentarium against inflammatory and immune-mediated ocular diseases. In order to better acquaint the ophthalmologist with the properties of the most commonly used immunosuppressive drugs, we review the literature and relate our own experience with these agents.
The onset of peripheral ulcerative keratitis in the course of a connective tissue disorder, such as rheumatoid arthritis, relapsing polychondritis, or systemic lupus erythematosus, may reflect the presence of potentially lethal systemic vasculitis. Moreover, peripheral ulcerative keratitis may be the first sign of systemic necrotizing vasculitis in patients with Wegener's granulomatosis, polyarteritis nodosa, microscopic polyangiitis, or Churg-Strauss syndrome. Although the exact pathogenesis of this severe corneal inflammation and destruction is not well understood, evidence points to a dysfunction in immunoregulation with immune complexes formed in response to autoantigens or to some unknown microbial antigen depositing in scleral and limbal vessels. These events lead to changes that are mainly responsible for the resulting tissue damage. In pauci-immune vasculitides positive for antineutrophil cytoplasmic antibodies, cell-mediated cytotoxicity may play an important role in the pathogenesis of peripheral ulcerative keratitis. Untreated systemic conditions such as those mentioned above may carry a grave prognosis for the eye and may also be life-threatening. Immunosuppressive therapy with corticosteroids and cytotoxic agents is, we believe, mandatory in the treatment of these multisystem disorders associated with vasculitic peripheral ulcerative keratitis.
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