The Acanthamoeba epidemic: what we have learned.
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Acanthamoeba Keratitis↗
Biomedical subjects
M J Mannis
Publications and source records attributed to M J Mannis.
Superficial hypertrophic dendriform epitheliopathy post-keratoplasty.
PURPOSE: To describe a distinct and unusual superficial dendriform keratopathy that can be seen in postkeratoplasty eyes. METHOD: Three Caucasian women in their sixth decade of life were referred to the Corneal and External Disease Service at the University of California, Davis, and underwent penetrating keratoplasty for different diagnoses. After keratoplasty, hypertrophic dendriform epithelial lesions were observed. These were refractory to debridement as well as topical antibiotic and steroid combinations. Immunofluorescent antibody testing was performed in all cases to rule out herpetic infection, and the patients were treated with nonpreserved lubricants and medications to eliminate medication toxicity as the cause of the lesions. RESULTS: All three patients in this series developed raised, hypertrophic epithelial lesions after keratoplasty, which were refractory to therapy. Comfort and mild increase in visual acuity were restored with the use of thin, moderate water content therapeutic contact lenses. CONCLUSIONS: Superficial hypertrophic dendriform epitheliopathy is a distinct syndrome that occurs postkeratoplasty in patients with preexisting chronic ocular inflammation, tear dysfunction, and/or lid disease exacerbated by the toxic effects of postoperative topical medication.
Corneal Diseases↗
Synergistic effect of substance P with epidermal growth factor on epithelial migration in rabbit cornea.
In order to investigate the role of neural regulation in corneal epithelial healing, we examined the effect of substance P (SP) on corneal epithelial migration using an organ culture system of rabbit corneas. We investigated the synergistic effects of SP with (1) growth factors: epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta(TGF-beta); (2) extracellular matrix proteins: fibronectin, vitronectin, laminin, and collagen type IV; and (3) cytokines: interleukin-1alpha (IL-1alpha), IL-1beta, and interleukin-6 (IL-6). Rabbit corneal blocks were cultured in the absence or presence of various reagents for 24 hr. The corneal blocks were then fixed, dehydrated, embedded in paraffin and stained by hematoxylin-eosin, and the length of the path of epithelial migration was measured. The addition of SP alone, at concentrations up to 50 microg ml-1, did not affect epithelial migration. EGF, fibronectin, vitronectin, collagen type IV, and IL-6 stimulated epithelial migration, but bFGF, TGF-beta, laminin, IL-1alpha, and IL-1betadid not. The stimulatory effect of EGF on the epithelial migration was enhanced by the presence of SP. This synergistic effect of SP and EGF on corneal epithelial migration was abolished by the addition of an SP antagonist or enkephalinase. Other neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acetylcholine chloride, norepinephrine, serotonin) and tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin) were examined, but none exhibited a synergistic effect with EGF. Interestingly, EGF alone stimulated the incorporation of 3H-thymidine into corneal epithelial cells, but the addition of SP with EGF did not enhance this effect. These results demonstrate that SP enhanced the EGF stimulation of corneal epithelial migration in vitro in a specific manner, suggesting a possible role of SP as a modulator of epithelial wound healing.
Animals↗
Superficial keratopathy in intensive care unit patients.
PURPOSE: To determine the prevalence of keratopathy in a randomly selected group of hospitalized patients in the intensive care unit and to identify factors associated with an increased incidence of corneal abnormalities. METHODS: We conducted bedside examinations with a portable slit lamp on 50 randomly selected patients. Evidence of superficial keratopathy was recorded. Associated factors analyzed included Glasgow Coma Scale, period in the intensive care unit, intubation status, underlying disease, and current eye care. RESULTS: Superficial keratopathy was present in 20 (40%) of the patients. Of these 20, 18 (90%) were intubated, whereas of the remaining 30 patients without corneal abnormalities, only 15 (50%) were intubated (P < .01). Fourteen (70%) of the 20 patients with corneal abnormalities had been hospitalized in the intensive care unit for 1 week or longer compared with 10 (33%) of the 30 patients without corneal abnormalities (P = .03). Twelve (60%) of the 20 patients with corneal abnormalities had Glasgow Coma Scale scores of 7 or less compared with seven (23%) of the 30 patients without corneal abnormalities (P < .03). Only one of the 20 patients with superficial keratopathy was receiving ocular lubrication. CONCLUSIONS: The prevalence of corneal abnormalities in the critically ill patient reflects certain predictors of keratopathy, including the Glasgow Coma Scale, length of hospitalization, intubation, and significant metabolic derangement. More ophthalmologic attention must be given to patients in intensive care units to prevent the development of ocular disease.
Adolescent↗
Corneal perforation associated with argon laser photocoagulation for a retinal tear.
PURPOSE: To report a corneal perforation during argon laser photocoagulation around a retinal tear following pneumatic retinopexy. METHODS: The patient was examined and found to have a corneal perforation with pigment in the base of the wound. To help explain this phenomenon, we evaluated the ability of argon blue-green laser to create a corneal perforation in a cadaver eye. RESULTS: In a cadaver eye, we induced a corneal perforation with argon laser only when a pigmented substance was present on the corneal surface. CONCLUSIONS: We hypothesize that pigmented material such as an eyelash or mascara caught between the cornea and contact lens interface may have facilitated this rare complication. Clinicians should be wary of any pigmented substance on the surface of the cornea or ophthalmoscopic lens when performing argon laser photocoagulation.
Aged↗
Comparison of astigmatism after penetrating keratoplasty by experienced cornea surgeons and cornea fellows.
PURPOSE: We compared surgically induced astigmatism after penetrating keratoplasty performed by supervised cornea fellows and experienced cornea surgeons. METHODS: Data were collected by retrospective chart review of 166 cases (166 eyes) of penetrating keratoplasty: 63 performed by two cornea surgeons and 103 by four cornea fellows. Astigmatism was calculated using scalar and vector methods. Vector analysis was performed on 109 of 166 eyes. Two techniques were compared: intraoperative keratometry and suture adjustment and the torque-antitorque running suture technique with no intraoperative keratometry or suture adjustment. RESULTS: Mean surgically induced scalar astigmatism changed from preoperative astigmatism by 3.27 diopters (fellows) and 2.94 diopters (attending surgeons). In 109 cases, surgically induced vector cylinder changed from peroperative astigmatism by 4.21 diopters at 98 degrees (fellows) and 4.25 diopters at 114 degrees (surgeons). Surgically induced vector astigmatism changed from preoperative astigmatism by 4.67 diopters at 93 degrees in the first 6 months (fellows) and by 3.79 diopters at 103 degrees in the second 6 months. Analysis of x-axis and y-axis components of the surgically induced vector cylinder showed that the majority of the astigmatism was induced in the y-axis and that this difference was significant (P < .001) in all comparisons, independent of technique or surgeon group. CONCLUSIONS: Penetrating keratoplasty performed by supervised cornea fellows resulted in similar rates of surgically induced vector astigmatism, surface asymmetry, and surface regularity as that by experienced surgeons. Fellows induced significantly more with-the-rule astigmatism, but this tendency decreased with further training. Penetrating keratoplasty astigmatic outcomes were not significantly different whether or not intraopertive keratometry and suture adjustment were utilized. This study supports the concept that increased experience with corneal transplantation improves the outcome of penetrating keratoplasty by using the criterion of postoperative astigmatism as a measures.
Astigmatism↗
Floppy eyelid syndrome in a child with chronic unilateral conjunctivitis.
PURPOSE: To report a 2-year-old child who had chronic unilateral conjunctivitis and spontaneous left upper eyelid eversion during sleep consistent with the floppy eyelid syndrome. METHODS: The patient's parents used a video camera to document nocturnal ectropion of the left upper eyelid. Examination demonstrated left upper eyelid swelling and left palpebral conjunctival hyperemia with papillary hypertrophy. RESULTS: All signs and symptoms of the floppy eyelid syndrome resolved with taping of the left upper and lower eyelids to close the palpebral fissure and to prevent ectropion during sleep, and with application of ocular lubricants. CONCLUSIONS: Floppy eyelid syndrome may manifest in childhood without other contributing conditions and should be considered in the differential diagnosis of chronic papillary conjunctivitis in patients at any age.
Child, Preschool↗
Preoperative risk factors for surface disease after penetrating keratoplasty.
We sought to identify the types of, prevalence of, and predisposing factors for the development of surface keratopathy after penetrating keratoplasty. We reviewed the records of 120 corneal grafts performed over a 15-month period. Twenty patients were excluded from the study. Fifty-three men and 47 women composed the group studied. All transplants were performed by the same surgeon. Retrospective data from patients' records were gathered preoperatively and from postoperative visits at 1 week and at 1, 2, 3, and 4 months. Data included preoperative medical and demographic data, operative time, postoperative medication regimens, assessment of the presence and degree, if present, of punctate epithelial keratopathy (PEK), hurricane keratopathy, macroepithelial defects, microcystic edema, bullous edema, and filamentary keratitis. In addition, information on the donor material was recorded. Surface disease and normal groups were compared to identify risk factors for the occurrence of surface abnormalities. Thirty-three of the patients demonstrated persistent surface abnormalities. Coarse PEK was the most common surface abnormality in the sample studied and was most prominent in the first week after surgery. Postoperative surface keratopathy was not statistically associated with preoperative diagnosis, donor age, death-to-preservation time, preservation-to-surgery time, or donor epithelial status. However, corneal recipients in the group with surface keratopathy were significantly older (mean, 68.7 years) than patients in the group with no surface abnormalities (mean, 52.6 years; Mann-Whitney U test, p < 0.001). Although many factors may contribute to the normal integrity of the corneal surface after keratoplasty, recipient age is of key importance in the development of surface disease.
Aged↗
Screening donor corneas that have undergone PRK.
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Contraindications↗
Delayed development of amiodarone keratopathy in a corneal graft.
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Aged↗
[Neurotrophic keratopathy--studies on substance P and the clinical significance of corneal sensation].
Neurotrophic keratopathy, which often follows damage to the trigeminal nerve, is clinically characterized by various types of epithelial disorders and melting of corneal stroma. To understand both the pathology of neurotrophic keratopathy and the physiological significance of corneal sensation, we investigated both the cellular and molecular functions of a sensory neurotransmitter, substance P, in corneal epithelial cells. Our findings prompted us to try a new mode of treatment for neurotrophic keratopathy. Substance P, a member of the tachykinin family, is an 11-amino-acid peptide. In an organ culture system using rabbit corneas, substance P alone had no effect on corneal epithelial migration. In the presence of insulin-like growth factor-1 (IGF-1), however, substance P synergistically facilitated corneal epithelial migration in proportion to the concentration of substance P or of IGF-1. Other neurotransmitters (acetylcholine, norepinephrine, serotonin etc.) or tachykinins (neurokinin A, eledoisin etc.) did not show this synergistic effect with IGF-1. Among receptors for the tachykinin family (NK-1, NK-2, or NK-3) only the NK-1 receptor system was involved in the synergistic effect of substance P and IGF-1 on corneal epithelial migration. IGF-1 affected neither the binding constant nor the number of sites of substance P receptors in corneal epithelial cells, suggesting that the synergistic effect was not regulated at the receptor level. Various extracellular signals activate the intracellular signal transduction system, thus amplifying specific biological functions. We found that the addition of inhibitors of protein kinase C or tyrosine kinase clearly inhibited the synergistic effect of substance P and IGF-1 on corneal epithelial migration, demonstrating that protein kinase C and tyrosine kinase are involved in the synergistic effect. During corneal epithelial wound healing, epithelial cells must attach to a provisional, extracellular fibronectin matrix. We previously reported that interleukin 6 and epidermal growth factor (EGF) facilitate corneal epithelial wound healing by activating the expression of fibronectin receptor (integrin). Reverse transcription-polymerase chain reaction (RT-PCR) revealed that substance P and IGF-1 increased expression of mRNA for integrins alpha 5 and beta 1 in cultured corneal epithelial cells and also increased the number of cells that attached to a fibronectin matrix. These findings strongly suggest that substance P and IGF-1 synergistically increase corneal epithelial migration by activating the expression of integrin. Tachykinins share a five amino acid sequence, phenylalanine-free amino acid-glycine-leucine-methionine amide (FXGLM), at the C-terminus. Studying substance P, we found that a four amino acid sequence at the C-terminus, FGLM, was the minimum amino acid sequence for the synergistic effect on corneal epithelial migration. Structurally similar tetrapeptides mimicking other members of the tachykinin family isoleucine-glycine-leucine-methionine amide (IGLM), valine-glycine-leucine-methionine amide (VGLM), tyrosine-glycine-leucine-methionine amide (YGLM), and the tripeptide glycine-leucine-methionine amide (GLM) did not have any synergistic effect with IGF-1. Based on these findings in vitro, we investigated the effect of eye drops containing substance P plus IGF-1 or FGLM plus IGF-1 on the epithelial wound closure of rabbit corneas in vivo. Both combinations significantly facilitated corneal epithelial wound closure. In a clinical setting, the administration of substance P plus IGF-1 effectively treated corneal epithelial defects in a patient with Riley-Day syndrome, a disease in which corneal epithelial defects persist because of loss of corneal sensation and hypolacrimation. In a patient with neurotrophic keratopathy due to trigeminal nerve paralysis following surgery, eye drops containing FGLM plus IGF-1 eliminated superficial punctate staining. (ABSTRACT TRUNCATED)
Animals↗
Synergistic effects of substance P with insulin-like growth factor-1 on epithelial migration of the cornea.
We find that substance P (SP) and insulin-like growth factor-1 (IGF-1) demonstrate a synergistic effect on the stimulation of rabbit corneal epithelial migration in an organ culture. The addition of either SP or IGF-1 alone did not affect epithelial migration, while the combination of SP and IGF-1 stimulated epithelial migration in a dose-dependent fashion. The synergistic effects of SP and IGF-1 on corneal epithelial migration were nulled by the addition of a SP antagonist or enkephalinase. Among neurotransmitters (vasoactive intestinal peptide, calcitonin gene-related peptide, acethylcholine chloride, norepinephrine, serotonin) or tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin), only SP demonstrated a synergistic effect with IGF-1 on cellular migration. In contrast, the combination of SP and IGF-1 did not affect the incorporation of 3H-thymidine into corneal epithelial cells. The attachment of the corneal epithelial cells to fibronectin, collagen type IV, and laminin matrices increased after treatment of the cells with SP and IGF-1, but SP or IGF-1 by themselves did not affect the attachment of the cells to these extracellular matrix proteins. An identical synergistic effect on corneal epithelial migration was observed when an NK-1 receptor agonist was used in place of SP, suggesting the synergistic effect of SP and IGF-1 might be mediated through the NK-1 receptor system. These results suggest that the maintenance of the normal integrity of the corneal epithelium might be regulated by both humoral and neural factors.
Animals↗
The use of synthetic Cecropin (D5C) in disinfecting contact lens solutions.
PURPOSE: Microbial keratitis caused by Pseudomonas aeruginosa is the most common contact lens associated corneal infection. Cecropins are microbicidal peptides isolated from the hemolymph of the Cecropia moth. Previous in vitro studies have demonstrated their efficacy against a broad spectrum of ocular pathogens. This study was designed: a) to evaluate the antimicrobial potency of three different contact lens solutions (Renu, Complete, and Opti-Free) against P. aeruginosa, and b) to evaluate the activity of the same contact lens solutions in combination with a synthetic cecropin analog, D5C, against the challenge organism in the presence of a soft contact lens. METHODS: A virulent strain of P.aeruginosa isolated from a case of ulcerative keratitis was used in the study. Three different concentrations of bacteria (10(3), 10(5) and 10(7) CFU/mL) were inoculated into the contact lens solutions and into buffered saline, which was employed as a control. The samples were incubated at 27 degrees C, and at time 0, 30, and 90 minutes, 24, 48, and 72 hours, and aliquots of the test solutions were plated and subcultured on nutrient agar. After 24 hours of incubation at 37 degrees C, colonies observed on the nutrient agar plates were counted. To study the antimicrobial efficacy of D5C (100 micrograms/mL), we used the identical test series and assay, adding a soft contact lens to the solutions and a larger inoculum of bacteria (10(9) CFU/mL). RESULTS: After 72 hours, all of the contact lens solutions tested sterilized 10(3) CFU/mL of P. aeruginosa. At 10(7) CFU/mL, they yielded greater than 2 logs of killing of the bacteria, but the solutions were not sterilized. The addition of D5C (100 micrograms/mL) to the contact lens solutions yielded greater than 3 logs of killing with a larger inoculum of bacteria in the presence of the soft contact lens. CONCLUSION: The contact lens solutions tested were effective against P. aeruginosa at 27 degrees C for up to 72 hours with an inoculum of 10(3) CFU/mL. The addition of D5C augmented their antimicrobial activity in the presence of the contact lens.
Colony-Forming Units Assay↗
Keratitis in methamphetamine abusers.
We report four cases of severe corneal ulceration in methamphetamine abusers. Methamphetamine abuse has been increasing in California and may exceed cocaine abuse in some regions. Methamphetamine's extensive physiologic effects, inconsistent street purity, and multiple routes of administration offer many possibilities for injury to the cornea. Potential causes of methamphetamine-related keratitis can be divided into four categories resulting from (a) direct pharmacologic and physical effects of methamphetamine; (b) the toxic effects of diluting or "cutting" agents such as lidocaine and quinine; (c) effects related to the route of drug administration (intravenous, inhalation, smoking); and (d) manufacture-related effects of exposure to unintentional caustic contaminants in the final product. The increasing prevalence of methamphetamine abuse and the severity of the associated ulcers should alert ophthalmologists to the problem of methamphetamine-related keratitis.
Adult↗
Factors influencing graft clarity.
Successful penetrating keratoplasty depends on both host- and donor-related factors. We compared the results of keratoplasty in a group with a wide range of donor ages to gauge the effect of donor age on graft success. We conducted a retrospective review of donor data, recipient age, preoperative diagnosis, and postoperative complications with respect to graft clarity at 24 months after surgery in 99 consecutive patients in an effort to determine the role of donor age in graft clarity. The only factors that we isolated that appeared to influence graft clarity at 24 months postoperatively were a preoperative diagnosis classified as inflammatory/traumatic and the occurrence of postoperative complications. There was no association between graft clarity and recipient age, donor age, death-to-preservation time, or preservation-to-surgery time.
Age Factors↗
Scleromalacia after retinal detachment surgery.
PURPOSE/METHODS: A 34-year-old man developed severe scleral thinning with imminent prolapse after conventional retinal detachment repair, including pars plana vitrectomy, endolaser photocoagulation, and perfluoropropane injection. Cadaveric dura mater was used to repair the scleral defect. RESULTS/CONCLUSION: The cause of scleromalacia in this case remains to be determined. Commercially prepared cadaveric dura mater can be successfully used as a tectonic graft for the treatment of scleral thinning.
Adult↗
Syphilis, serologic testing, and the setting of standards for eye banks.
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Eye Banks↗
In vitro antimicrobial activity of Shiva-11 against ocular pathogens.
Cecropins are antimicrobial peptides (30-35 amino acids) isolated from the hemolymph of the cecropia moth. Previous studies have demonstrated their antimicrobial efficacy against a variety of pathogens, including both gram-positive and -negative bacteria, fungi, protozoa, and enveloped viruses. To assess their therapeutic potential against ocular pathogens, we analyzed the in vitro antimicrobial activity of a synthetic cecropin analog, Shiva-11, against virulent microbial strains (Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, and Candida albicans). Bacterial isolates were obtained from human cases of severe ulcerative keratitis. Shiva-11 was tested at varying concentrations in bacterial suspensions containing 1-2 x 10(6) CFU/ml at 37 degrees C. Samples were plated on nutrient agar and colonies counted after 24-48 h of incubation. Shiva-11 yielded > 3 log killing of all isolates after 60 min of exposure to this compound. The results of this study indicate that Shiva-11 possesses broad-spectrum in vitro antimicrobial activity against human clinical ocular pathogens.
Animals↗