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Biomedical subjects

K R Kenyon

Publications and source records attributed to K R Kenyon.

At least 145 records · Page 8Linked to original sources

Corneal endothelial function and structure following cryo-injury in the rabbit.

Wide-field specular microscopy, fluorophotometry, pachymetry, and scanning electron microscopy are used to characterize a reproducible, in vivo model of corneal endothelial injury and recovery in the rabbit. Following an 8-mm central cryo-injury, the cornea remains thickened for as long as 3 weeks. Mean endothelial permeability to fluorescein is above normal for 10 days following injury, but by 14 days postinjury the endothelial permeability to fluorescein is not statistically significantly different from preinjury control values, thus indicating that endothelial permeability probably returns to normal by approximately 2 weeks postinjury. Cell morphology, as determined by scanning electron microscopy, is also essentially normal by 2 weeks postinjury. Endothelial permeability appears to recover before stromal thickness normalizes, suggesting a lag in recovery of endothelial pump function.

Animals↗

Retinal toxicity of intravitreal gentamicin. An electron microscopic study.

Retinal ultrastructure was examined at various intervals following a single intravitreal injection of 100-4,000 micrograms of gentamicin in rabbit eyes. Three days after injections of 100-500 micrograms, numerous abnormal lamellar lysosomal inclusions were observed in the retinal pigment epithelium (RPE) and in macrophages in the subretinal space. These changes were typical of drug-induced lipid storage and were comparable to inclusions reported in kidney and other tissues as manifestations of gentamicin toxicity. One week after similar injections, focal areas of RPE necrosis and hyperplasia with disruption of outer segments appeared, but the inner segments and inner retina were intact. Doses of 800-4,000 micrograms produced a combined picture of RPE/macrophage lipidosis within the first 3 days, with increasing, superimposed, inner, retinal necrosis. This study provides the first evidence of lysosomal alterations in ocular tissues following the intravitreal injection of gentamicin and implicates the RPE as the primary site of observed toxicity.

Animals↗

Corneal and conjunctival effects of monobenzone in patients with vitiligo.

Monobenzone (the monobenzyl ether of hydroquinone [Benoquin]) is used topically by patients with extensive vitiligo to depigment their remaining normally pigmented skin. A patient who had been applying the drug for one year had an anterior linear deposition of pigment in both corneas. Of 15 additional patients with vitiligo, 11 of whom were using monobenzone, acquired conjunctival melanosis in two patients and pingueculae in three may have been related to monobenzone use. Light and electron microscopy of one corneal epithelial scraping and 12 conjunctival biopsy specimens revealed pleomorphic, single-membrane-limited intracytoplasmic inclusions within the corneal epithelium and within the epithelium, fibrocytes, histiocytes, and vascular endothelium of the conjunctiva. The ultrastructural aspects of these inclusions suggested that they are residual bodies containing lipid and lipofuscin.

Adult↗

Increased tear evaporation in eyes with keratoconjunctivitis sicca.

The terms dry eye and keratoconjunctivitis sicca (KCS) imply a condition of highly reduced or absent tear film that often is not clinically demonstrable despite the presence of other signs and symptoms. In 52 patients with KCS symptoms, either with or without tear volume reduction as measured by Schirmer's basic secretion test, we found a statistically significant increase in water evaporation rate from the tear film when compared with normal subjects. Such an increased evaporation rate might account for the tear hypertonicity known to be associated with KCS and postulated to be responsible for ocular surface damage. Thus, we propose to identify this group of paradoxically wet "dry eyes" as a "syndrome of increased tear evaporation", which better describes the pathogenesis of the ocular condition.

Adult↗

Effects of prednisolone and medroxyprogesterone on corneal wound healing, ulceration, and neovascularization.

Albino rabbits were treated four or six times daily with 1% prednisolone acetate, 1% medroxyprogesterone acetate, or a control vehicle, after one of three conditions. First, after 3-mm linear perforating stromal incisions; drugs were given for seven days, and wound bursting strength was determined. Prednisolone suppressed wound tensile strength by 20%; medroxyprogesterone suppressed it by 11%. Second, after trephination, drug administration for 14 days decreased collagen formation in the scar buttons by 43% in the prednisolone-treated group and 39% in the medroxy-progesterone-treated group. Third, after thermal burns; when drug application followed the burn immediately, deep ulceration or perforation developed in 85% of the controls, in none of the prednisolone-treated group, and in 17% of the medroxyprogesterone-treated group. When drug delivery was withheld until day 6, severe ulceration developed in 44% of both groups. In both experiments, stromal neovascularization was markedly suppressed by prednisolone, but only moderately decreased by medroxyprogesterone.

Animals↗

Intracorneal lens implantation.

In previous experiments, we found that a high-water-content hydroxyethyl methacrylate (Permalens) hydrogel implant was not only well tolerated within the rabbit corneal stroma but also would successfully alter the anterior radius of curvature, and thus the refractive state, of the rabbit eye. The same lens material implanted in the cornea of a patient with aphakic bullous keratopathy was tolerated for six months and decreased epithelial edema but did not alter the refractive state. This cornea, containing the intrastromal lens, was obtained at subsequent penetrating keratoplasty and studied by light and transmission electron microscopy. Morphologically, the epithelium and anterior stroma were not edematous, whereas the stroma posterior to the lens remained edematous. Minimal fibroblastic activity was evident at the lens-stroma interface. There were no signs of inflammation, ulceration, or neovascularization.

Aged↗

Histopathology of Sanfilippo's syndrome.

A 19-year-old woman with Sanfilippo's syndrome had poor vision, a flat electroretinographic pattern, and fundus changes similar to those in retinitis pigmentosa. Histology of her eyes by phase-contrast and electron microscopy showed extensive intracellular accumulation of fibrillogranular and membranous lamellar vacuoles in cornea, trabecular meshwork, iris, lens, ciliary body, and sclera. Retinal ganglion cells, retinal pigment epithelium (RPE), and optic nerve glia were similarly involved. Retinal pigment epithelial hyperplasia and hypopigmentation, intraretinal RPE migration, vascular attenuation, and marked photoreceptor loss were notable and closely resembled that occurring in inherited retinitis pigmentosa. We assume that the patient's blindness was due to photoreceptor cell loss, since the ganglion cells and optic nerve seemed to be intact. Although the cause of photoreceptor loss is unclear, the massive storage of acid mucopolysaccharide and lipofuscin within the RPE might disturb its essential metabolic functions and lead to photoreceptor degeneration.

Adult↗

Ultrastructure of mast cells in rat ocular tissue undergoing anaphylaxis.

In a study of ocular tissues undergoing anaphylaxis, in uninjected rats most mast cells contained electron-dense granules with no discernible internal structure. A few cells showed varying degrees of swelling of the matrix granules. In rats injected with normal rabbit serum, more mast cells showed swelling of the granule matrix and a few showed extensive swelling of nearly all granules. Mast cells from rats undergoing anaphylaxis by either anti-IgE or antigen injection showed membrane and granule alterations: extensive dendritic processes, fusion of granule membranes, fusion between granule and plasma membranes, and disruption of plasma membranes. Communication was established between the exterior of the cell and contents of individual granules of cisternae formed by several fused granules. The matrix of nearly all granules was extensively swollen.

Anaphylaxis↗

Superinfections in herpes simplex keratitis.

We reviewed 15 cases of culture-proven corneal superinfections in 15 patients (eight men and seven women ranging in age from 41 to 86 years) with recurrent herpes simplex keratitis. The factors that appeared to increase the risk of superinfection were the presence of an epithelial defect (found in all 15 cases), a history of recurrent herpetic keratouveitis (found in ten cases), and the use of topical corticosteroids (found in 13 cases). Eight of the 15 patients were taking antibiotics at the time the superinfections were diagnosed, indicating that topical antibiotics do not provide sufficient protection. Gram-negative rods were found in six cases (Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens, Klebsiella oxytoca, Enterobacter cloacae, and Achromobacter sp.). Gram-positive organisms, often in association with another infecting agent, were found in six cases (Staphylococcus epidermidis, three cases; S. aureus, two cases; and Streptococcus sp., two cases). Fungal superinfections were found in three cases (Cephalosporium acremonium, Candida albicans, and Aspergillus fumigatus, one case each). Mycobacterium cheloni was found in two cases.

Administration, Topical↗

Superior limbic keratoconjunctivitis in contact lens wearers.

Forty patients with daily wear, cosmetic contact lenses (CL) presented with symptoms of ocular irritation and a keratoconjunctivitis clinically resembling superior limbic keratoconjunctivitis (SLK). Typically the patients were either successful hard CL wearers who changed to soft lenses and used a chemical aseptisizing solution or preserved saline solution, or successful soft CL wearers using salt tablets who switched to a preservative-containing system. In all cases, exposure to thimerosal-preserved solutions was documented. Upon discontinuation of lens wear, all signs and symptoms slowly resolved without permanent sequelae. Positive skin and ocular sensitivity reactions to thimerosal were present in one-third (5/15) of patients tested. Light and transmission electron microscopic examination of conjunctival specimens disclosed intercellular epithelial edema, pseudoepitheliomatous hyperplasia, acute and chronic inflammation, and decreased numbers of goblet cells. Exposure to thimerosal is implicated in the etiology of contact lens-superior limbic keratoconjunctivitis (CL-SLK).

Adolescent↗

Ocular manifestations of graft-vs-host disease.

In patients who have graft-vs-host disease (GVHD) after bone marrow transplantation, ocular involvement occurs in approximately 60% of cases. Among 13 such GVHD patients, the most frequent ocular manifestations included keratoconjunctivitis sicca, cicatricial lagophthalmos, and sterile conjunctivitis and uveitis. The severe ocular complications of persistent corneal epithelial defects and both noninfected and infected stromal ulceration were related to the concomitant dry-eye condition and could be managed by conventional therapy including topical lubricants and antibiotics, punctal occlusion, bandage soft contact lenses, tarsorrhaphy, tissue adhesive, conjunctival flap, and conjunctival homograft. Postmortem and surgical tissues from four patients revealed conjunctival and corneal epithelial thinning and keratinization, lacrimal inspissation without inflammatory infiltration, and diffuse choroiditis. Keratoconjunctivitis sicca in GVHD patients might be a combined result of drug toxicity effects and GVHD. The frequent and potentially severe ocular problems in these patients suggest that close ophthalmic monitoring is mandatory in bone marrow transplant recipients.

Adolescent↗

Paraphenylenediamine: a new method for tracing human visual pathways.

Morphologic investigations of the human visual pathways have been limited by the infeasibility of modern neuroanatomical approaches. Although contemporary methods for tracing axon pathways (such as tracer injections and electrophysiology) have elucidated the visual system in experimental animals, these techniques cannot be similarly applied in humans. Thus, the present view of the neuroanatomy of the human visual system is based largely on experimental animal studies, classical simple observations of gross human brains, and clinical inference. We demonstrate use of the stain, paraphenylenediamine (PPD), in conjunction with standard methods of tissue preparation for transmission electron microscopy. Osmium precipitates on degenerating neural processes, resulting in a dark profile when examined by electron microscopy. PPD chelates the osmium in osmium tetroxide-fixed tissue, and thus becomes a light-opaque marker of degenerating processes. This technique allows the identification and tracing of degenerating or degenerated axons. Postmortem studies of six patients, four with documented optic nerve lesions, are presented. The degenerated retinal ganglion nerve fibers are followed with PPD and confirmed with electron microscopy. Previously proposed, primary visual projections are confirmed and new retinofugal pathways are demonstrated in the human brain.

Adult↗

Epibulbar IgA plasmacytoma occurring in multiple myeloma.

The ophthalmic manifestations of a 51-year-old man with multiple myeloma included exudative retinal detachments and multiple epibulbar plasmacytomas. The retinal changes resolved with treatment for systemic effects, and the IgA-producing plasmacytomas rapidly resolved with local irradiation. The young age of onset (37 years), the prolonged course (14 years), and the IgA M protein and epibulbar involvement were, collectively, unusual findings in multiple myeloma. The presence of epibulbar, gastrointestinal tract, and prostate involvement suggested a homing mechanism of IgA-committed cells to mucosal surfaces.

Adult↗

Clinicohistopathologic correlations in xerophthalmic ulceration and necrosis.

Corneal tissue from five eyes of three children with active xerophthalmic keratopathy and stromal loss was studied histopathologically. Stromal dissolution was strikingly focal, sometimes occurring beneath an intact epithelium and often, though not always, accompanied by extensive inflammatory reaction and bacteria.

Child↗

Asteroid hyalosis. Biomicroscopy, ultrastructure, and composition.

The vitreous in 16 patients (average age, 65 years) with asteroid hyalosis was studied and photographed using a preset lens (El Bayadi-Kajiura) and slitlamp. Asteroid hyalosis was bilateral in one patient (6%) and unilateral in 15 patients (94%). The gel was biomicroscopically normal in 13 patients (81%) and showed moderate liquefaction in three patients (19%). In ten (63%) of the 16 patients, there was no posterior vitreous detachment, in four patients (25%), there was partial vitreous detachment, and in two patients (12%), there was complete vitreous detachment. The preponderance of complete vitreous detachment was lower than expected for patients in this age group, probably because of a reduced preponderance of vitreous liquefaction in patients with asteroid hyalosis. A vitreous aspirate from one of these patients was studied using phase-contrast microscopy and scanning and transmission electron microscopy. Asteroid bodies were enmeshed within normal vitreous collagen fibrils and some were attended by macrophages or multinucleated epithelioid cells. Transmission electron microscopy disclosed irregular calcific material and complex lipids within the asteroid bodies. X-ray spectroscopy demonstrated calcium and phosphorus.

Aged↗

Immunosuppression and selective inflammatory cell depletion. Studies on a guinea pig model of corneal ulceration after ocular alkali burning.

Total ocular-surface alkali burning was performed on guinea pigs to study the effects of generalized immunosuppression and selective inflammatory cell line modifications on corneal ulceration. Central stromal corneal ulceration developed in 86% (18/21) of control eyes three to seven days after alkali burning, whereas ulcers developed in only 16% (3/19) of the eyes of guinea pigs immunosuppressed with cyclophosphamide. Neutrophils, the preponderant inflammatory cells in ulcerating corneas, were conspicuously absent from the nonulcerating corneas. Selective neutrophil suppression by intravenous administration of a highly specific anti-guinea pig neutrophil serum also suppressed the development of corneal ulcerations in this model; in only 25% of the eyes so treated did ulcers develop after alkali burning. T lymphocyte or monocyte modifications with similar monospecific antisera had no effects on the rate of corneal ulceration. Neutrophil depletion after the onset of ulceration halted progression of the corneal ulcer.

Animals↗

Decision-making in the therapy of external eye disease: noninfected corneal ulcers.

Despite diverse and multiple clinical etiologies, the pathogenesis of noninfected corneal ulcers consistently relates to persistent or extensive epithelial defects, concomitant with stromal inflammatory cell infiltration and enzymatic degradation of collagen and ground substance. The therapeutic approaches to these disorders may be considered on three levels: (1) the determination of etiology and initiation of primary therapy; (2) promotion of epithelial healing; and (3) limitation of ulceration and support of repair, the latter aspects currently featuring pharmacologic management and limited surgical modalities, particularly the use of tissue adhesive.

Adult↗