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Biomedical subjects

K R Kenyon

Publications and source records attributed to K R Kenyon.

At least 19 recordsLinked to original sources

Microbial contamination of in-use ocular medications.

Two hundred twenty in-use medications from 101 patients with nonmicrobial ocular surface disease were studied by culturing the bottle caps, a drop produced by simple inversion, and the interior contents removed sterilely. Conjunctival cultures were taken from these patients and 50 age-matched controls. Pathogenic organisms were harvested from conjunctivae significantly more frequently (P less than .01) from cases (34 of 101) than from controls (five of 50). Sixty-four medications (29%) had microorganisms cultured from at least one medication site. Gram-negative organisms were significantly more likely (P less than .00001) to be isolated from all medication sites than gram-positive organisms. Additionally, when isolated from medication sites, the gram-negative organisms were highly likely to be cultured from the conjunctiva as well. This was not true for pathogenic gram-positive organisms. We conclude that a cycle of contamination between in-use medications and conjunctivae may represent an important risk factor for microbial keratitis in patients with ocular surface disease.

Conjunctiva

Penetrating keratoplasty and anterior segment reconstruction for severe ocular trauma.

The authors reviewed 39 consecutive cases of severe ocular trauma that had undergone penetrating keratoplasty plus anterior segment reconstruction and evaluated visual outcome, graft survival, and secondary complications. Postoperatively, 49% of eyes achieved visual acuity of 20/100 or better compared with 10% before surgery, and 72% improved at least 2 Snellen lines. With a mean follow-up of 23 months, 31 (80%) initial keratoplasties remained clear, and all 4 subsequently re-grafted corneas maintained clarity, for an overall keratoplasty success rate of 90%. Elevated intraocular pressure occurred postoperatively in 18 eyes (46%), and, among these, 10 of 13 eyes (77%) had preoperative glaucoma, whereas 8 of 26 (31%) did not (P less than or equal to 0.015). Preoperative anterior synechiae could be anatomically corrected at surgery in 80% of cases (24 of 30 eyes). In 7 cases with persistent synechiae, 6 (86%) were associated with glaucoma (P less than or equal to 0.025). Retinal detachment occurred in one case. Thus, despite major trauma and a high prevalence of glaucoma, both the visual restoration and anatomic reconstruction achieved were satisfactory and without severe complications.

Adolescent

In vitro adhesion of Pseudomonas aeruginosa and Staphylococcus aureus to surface passivated poly(methyl methacrylate) intraocular lenses.

Bacterial attachment to intraocular lenses (IOLs) can be a cause of infectious endophthalmitis following cataract surgery. In this study, Pseudomonas aeruginosa and Staphylococcus aureus adhered in vitro to untreated poly(methyl methacrylate) (PMMA) and to surface passivated PMMA lenses. The IOLs were placed in bacterial suspensions (1 x 10(7) cfu/ml) in vitro. Significantly fewer S. aureus attached (P < .05) to the normal PMMA IOLs (4,535 +/- [SD] 3,052 bacteria/mm2) and to passivated PMMA IOLs (8,720 +/- 10,040 bacteria/mm2) than did P. aeruginosa (normal PMMA: 67,808 +/- 45,070 bacteria/mm2, passivated PMMA: 85,795 +/- 70,647 bacteria/mm2). The differences in bacterial attachment to surface passivated IOLs and to untreated PMMA lenses were not significant.

Bacterial Adhesion

Eicosanoid modulation and epithelial wound healing kinetics of the alkali-burned cornea.

The cyclooxygenase and lipoxygenase enzyme systems can metabolize a number of C20 polyunsaturated fatty acids. Although arachidonic acid is the usual substrate for these pathways, the eicosanoid precursor pool can be nutritionally manipulated by supplementation with alternative precursors, often generating less active or down-regulatory metabolic products. Prefeeding with gamma-linolenic acid, eicosapentaenoic acid, or a combination of both failed to influence the lagphase, epithelial migration rate, or epithelial wound healing kinetics after either 1N or 4N NaOH alkali burning of the rabbit cornea. Initial epithelial wound healing probably does not involve eicosanoid-mediated processes. Essentially linear epithelial healing kinetics continued to closure without a late decrease in wound edge velocity.

Alkalies

Proteolytic activation of corneal matrix metalloproteinase by Pseudomonas aeruginosa elastase.

Purified Pseudomonas aeruginosa elastase cleaved a 65 kDa gelatinase [inactive proenzyme form of matrix metalloproteinase (MMP-2)] from human corneal fibroblasts into a biologically active fragment with an approximate molecular mass of 58 kDa. However, purified pseudomonal alkaline protease did not cleave MMP-2 appreciably. Since activated MMP-2 is known to degrade native type IV, V and VII collagens, all components of the corneal basement membrane or stroma, our results suggest a new role for pseudomonal elastase in the pathogenesis of corneal infection, inflammation and ulceration.

Alkaline Phosphatase

[Metabolic analysis of the diseased human corneal endothelium].

Redox states of the corneal endothelium in 42 recipient corneas obtained at the penetrating keratoplasty were measured non-invasively using ocular redox fluorometry. Autofluorescence from reduced pyridine nucleotides (PN) and oxidized flavoproteins (Fp) were measured, and the PN/Fp ratio was used as an indicator of the redox state. Endothelial damage was graded as normal, mildly damaged, moderately damaged, and severely damaged, based on the histopathological findings. Mildly damaged endothelium showed a significantly higher PN/Fp ratio than the that in normal endothelium whereas the ratio was significantly lower in the severely damaged endothelium. These changes in the redox state may represent compensation and decompensation processes of the endothelial metabolism. Ocular redox fluorometry was shown to be useful for the evaluation of the metabolic state in the human corneal endothelium.

Adult

The incidence of ulcerative keratitis among aphakic contact lens wearers in New England.

We conducted a population-based incidence study in five New England states to quantify the risk of ulcerative keratitis associated with contact lens use among aphakic persons. All practicing ophthalmologists in the five-state area were surveyed to identify prospectively all new cases of ulcerative keratitis during a 4-month period. The number of aphakic persons using specific types of contact lenses was estimated through a telephone survey of 4178 households identified by random digit dialing. The annualized incidence of ulcerative keratitis among aphakic persons using contact lenses was estimated to be 52 cases per 10,000 aphakic contact lens wearers (95% confidence interval (CI), 31.1 to 86.9). The risk of ulcerative keratitis varied substantially by lens use, with extended wear having an estimated sevenfold greater risk relative to daily wear (95% CI, 1.6 to 30.2). Rates of ulcerative keratitis in aphakic persons using contact lenses were much greater than rates among cosmetic wearers of the same lens type: for daily-wear lenses, aphakic persons were estimated to have 6.3 times the risk of cosmetic wearers (95% CI, 1.9 to 21.0), and for extended-wear lenses, aphakic persons were estimated to have 8.7 times the risk of cosmetic wearers (95% CI, 3.5 to 21.9). These risks are useful in assessing the benefits and risks of contact lens wear as an alternative to other methods of aphakic correction.

Adolescent

Clinical and histopathologic studies of two families with lattice corneal dystrophy and familial systemic amyloidosis (Meretoja syndrome).

Lattice corneal dystrophy associated with familial systemic amyloidosis (Meretoja syndrome) has rarely been described other than in patients of Finnish origin. The authors report two North American patients with this disease who manifest blepharochalasis, lattice corneal dystrophy, open-angle glaucoma, and cranial neuropathy. In one patient, a corneal intraepithelial and subepithelial pseudodendrite was managed by superficial keratectomy, and this same patient benefited from surgical brow suspension for facial muscular weakness. In the second patient, penetrating keratoplasty was complicated by a neurotrophic persistent epithelial defect. Corneal tissue from both superficial keratectomy and penetrating keratoplasty exhibited ultrastructurally characteristic amyloid filaments and associated elastoid material. Transmission electron microscopy of conjunctiva and skin biopsies similarly revealed amyloid deposits associated with most basement membranes, the perineurium and endoneurium of most peripheral nerves, and the intima and media of arteries. By immunoperoxidase staining, the corneal amyloid deposits were positive for the amyloid P-component protein but negative for the nonimmunoglobulin amyloid A protein and prealbumin. Serum prealbumin and amyloid A related protein were normal.

Aged

A spectrum of bilateral squamous conjunctival tumors associated with human papillomavirus type 16.

Three patients with bilateral tumors presenting as multiple keratinizing and verrucous lesions of the bulbar and tarsal conjunctiva were determined by DNA amplification and hybridization studies to harbor human papillomavirus type 16 (HPV-16). Results of biopsy in two patients showed infiltrating squamous cell carcinoma in one eye and dysplasia or carcinoma in situ in the fellow eye. In the third patient, focal, inflamed, hypertrophic, papillary lesions with pseudoglandular invaginations of the surface epithelium were found in the tarsal conjunctivae of both eyes. These are the first documented cases of bilateral conjunctival tumors associated with human papillomavirus.

Adult

Penetrating keratoplasty for severe complications of radial keratotomy.

Severe sight-threatening complications were seen in five eyes of three patients following improperly performed radial keratotomy. All patients exhibited neovascularization of the incision sites, severe stromal scarring or ulceration involving the visual axis, loss of the anterior chamber, and iridocorneal adhesions. These complications necessitated multiple and complex surgical interventions, including penetrating keratoplasty and anterior segment reconstruction. Final visual acuity was decreased to light perception in four eyes while one eye achieved 6/60 vision following repeated penetrating keratoplasty. The success and safety of radial keratotomy rely on careful case selection, appropriate instrumentation, specialized training, and the ability to perform complex secondary procedures to correct surgical complications.

Adult

Conjunctival autograft for primary and recurrent pterygia: surgical technique and problem management.

The surgical technique and postoperative problem management of conjunctival autograft transplantation for advanced primary and recurrent pterygium are reviewed. Problems such as graft edema, corneoscleral dellen, and epithelial inclusion cysts infrequently occur. Corneal astigmatism, Tenon's granuloma, retraction and/or necrosis of the graft, and muscular disinsertion are even less frequently encountered. Limbal-conjunctival autograft for recalcitrant recurrent cases is proposed.

Astigmatism

Pathogenesis of corneal epithelial defects: role of plasminogen activator.

Previous studies have suggested that the plasminogen activator (PA)/plasmin system has important roles in the pathogenesis of epithelial defects and stromal ulceration. The current studies were performed to localize PA species and identify them as tissue-type PA (tPA) or urokinase-like PA (uPA) as the two have distinct regulatory properties potentially related to the mechanisms of defect formation and ulceration. To determine the locations and types of PA species, antibodies to tPA or to uPA or the drug amiloride (a drug that inhibits uPA but not tPA) were incorporated into fibrin/fibronectin (Fn) clots overlying frozen sections to block regional fibrinolysis. Normal rabbit eyes showed tPA activity in association with corneal epithelium, corneal endothelium, and ciliary body/iris. After epithelial scrape or alkali burn, corneal tPA activity was detected initially in the defect zone colinear with fibrin/Fn and was symmetrical to resurfacing epithelium. The observation that initial fibrinolysis occurs in the defect zone, known to contain fibrin/Fn, suggests that tPA from blood (limbal vascular endothelium) and/or from corneal epithelium has become bound to (and activated on) the fibrin/Fn. PA activity was also associated with the leading edges of migrating epithelium post-scrape and post-burn and was not inhibited by antibodies to either tPA or uPA but was inhibited by amiloride. After complete closure of the primary defect post-scrape, only tPA appeared to be associated with the epithelium in that all PA activity was inhibited by antibodies to tPA. The observation that leading edge activity post-burn, in correlation with the formation of secondary defects, continues to be inhibitable by amiloride but not by antibodies to tPA suggests that uPA remains abnormally on the leading edge, and that sustained uPA activity in that location results in inappropriate degradation of subepithelial fibrin/Fn to result in a defect. Successful regulation of uPA activity at the leading edge of corneal epithelium post-burn would be expected to be useful therapeutically in the healing of epithelial defects and the prevention of stromal ulceration.

Animals

Change of paracellular permeability of ocular surface epithelium by vitamin A deficiency.

Dietary vitamin A deficiency in young rabbits caused advanced squamous metaplasia with keratinization of conjunctival epithelium and concomitant reduced paracellular permeability to 3H-mannitol. Both morphologic and permeability changes were reversed with systemic administration of vitamin A. In adult rabbits, vitamin A deficiency caused milder changes of goblet cell loss and increased cellular stratification in conjunction with reduced permeability in the conjunctiva-like epithelium that covers the vascularized cornea after chemical injury with n-heptanol. Topically applied retinoid (tretinoin 0.1%) did not affect the morphology and permeability of the normal corneal or conjunctival epithelium of rabbits that were not vitamin A deficient. These studies showed that altered permeability is associated with the epithelial abnormality during vitamin A deficiency and helped clarify the physiologic function of retinoids in the ocular surface epithelia in the nondeficient state.

Administration, Topical

Pseudomonas attachment to low-water and high-water, ionic and nonionic, new and rabbit-worn soft contact lenses.

The authors determined the attachment of a single strain of Pseudomonas aeruginosa to seven brands of hydrogel soft contact lenses (SCLs): nonionic, low-water (polymacon and crofilcon); nonionic, high-water (lidofilcon); ionic, high-water (bufilcon, etafilcon, and perfilcon); and surface-neutralized, high-water (bufilcon). The lenses were exposed to a 1 X 10(8) colony-forming units (CFU)/ml P. aeruginosa suspension either when new and sterile or after 24 hr of continuous wear in rabbit eyes. Quantitative scanning electron microscopy showed that, regardless of lens type, significantly fewer bacteria attached to worn than to new SCLs (P less than 0.05). The bacterial attachment on new, unworn SCLs was significantly lower (Wilcoxon rank-sum test) (P less than 0.05) on polymacon and crofilcon than on all other lenses tested except perfilcon; on etafilcon than on bufilcon; and on perfilcon than on all SCLs tested except polymacon. The bacterial attachment on rabbit-worn SCLs was significantly lower (P less than 0.05) on polymacon than on all other lenses tested except crofilcon and perfilcon; on crofilcon than on bufilcon; on lidofilcon and on surface-neutralized bufilcon than on crofilcon and perfilcon; on etafilcon than on crofilcon, bufilcon, and perfilcon; and on perfilcon than on crofilcon and bufilcon. The results did not show a consistent relationship between hydration and surface charge and P. aeruginosa adherence. Among the SCLs tested, no one lens had a decisive advantage over another, because all, both new and worn, can bind amounts of P. aeruginosa that could potentially produce bacterial keratitis on predisposed eyes.

Animals

Effect of fibronectin on corneal epithelial wound healing in the vitamin A-deficient rat.

The authors investigated the in vitro and in vivo effects of fibronectin (Fn) on the migration of corneal epithelium of vitamin A-deficient (A-) and pair-fed control (A+) rats. Groups treated with 50 micrograms/ml Fn showed accelerated healing of epithelium in vitro (P less than 0.05) compared with control groups of A- and A+ rats. However, when 100 micrograms/ml Fn eye drops were administered 14 times over 20 hr, they had no significant effect on A+ rats in vivo, but increased the healing in A- rats (P less than 0.05). In this model, Fn promoted the healing of corneal epithelium under A- conditions where decreased endogenous Fn is seen, whereas A+ corneas in vivo, which have sufficient Fn over the wound surface, did not benefit from topical Fn administration.

Administration, Topical

Alteration of epithelial paracellular permeability during corneal epithelial wound healing.

We studied the paracellular permeability to mannitol of corneas with epithelium of corneal, limbal, or conjunctival origin. Corneas with epithelial defects reepithelialized by corneal or limbal epithelium were nonvascularized; the corneal permeability was initially increased and returned to normal 3 days later. When epithelial defects extended beyond the limbus, they were healed by conjunctival epithelium. If corneas remained avascular or minimally vascularized, the conjunctiva-derived epithelium underwent a transdifferentiation process into a cornealike morphology in which the corneal permeability was initially increased upon complete reepithelialization, and gradually decreased to a level similar to that of normal cornea, 4 weeks after healing. However, when corneas became vascularized, the conjunctiva-derived epithelium retained its original phenotype, and corneal permeability remained increased throughout the 8-month period of study. The deranged barrier functions noted in the above vascularized cornea were demonstrated further by horseradish peroxidase tracer, which was found in the intercellular spaces of conjunctiva-derived epithelium of vascularized corneas but not in the avascular corneas with epithelia of corneal or limbal origin, or transdifferentiated conjunctival epithelium. To study further the effect of subsequent ocular surface trauma, conjunctival biopsy was performed on transdifferentiated avascular corneas 3 months after initial wounding. The biopsy resulted in extensive vascularization in three of eight previously nonvascularized corneas. Two weeks later, the corneal permeability was increased to a level similar to that of conjunctiva. These results indicate that corneal epithelial paracellular permeability correlates well with the status of the epithelial phenotype.

Animals

Corneal surface irregularities and episodic pain in a patient with mucolipidosis IV.

Mucolipidosis IV is a lysosomal storage disease characterized by prominent involvement of the corneal epithelium. A 5-year-old boy with mucolipidosis IV experienced recurrent episodes of severe ocular pain, tearing, and ipsilateral facial flushing. This was suggestive of reflex sympathetic dystrophy, a syndrome of pain and sympathetic hyperactivity. The examination revealed marked corneal surface irregularities, corresponding to massive accumulations of intracytoplasmic storage material in the epithelium. Episodic pain in patients with mucolipidosis IV is an important symptom, presumably reflecting the distinctive corneal ultrastructural abnormality in this disease.

Cataract Extraction