Chlorhexidine or polyhexamethylene biguanide for acanthamoeba keratitis.
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Biomedical subjects
Publications and source records attributed to C M Kirkness.
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Infectious endophthalmitis is a serious ocular condition which always requires rapid medical or surgical intervention. At present this, in a number of situations, remains empirical as a consequence of problems inherent in unequivocal identification of the causative organism, should one be present. Aqueous humor smears and culture have limited value in diagnosis. Vitreous samples can often reveal the presence of microbes, but these may not necessarily be detected in all cases, principally due to suboptimal sampling or pretreatment with antimicrobials which render microbes non-culturable on routine media. Use of electron microscopy and/or immunocytochemistry offers an alternative means of identification, but these approaches have drawbacks principally associated with interpretation. Molecular methods which identify conserved sequences from common causative microbes of endophthalmitis, or which can specify whether the organism is a bacterium or a fungus may become especially important as diagnostic tools in this clinical scenario.
The iridocorneal-endothelial syndrome (ICE syndrome) is characterised by corneal failure, glaucoma and iris destruction. Specular photomicroscopical and histological studies of the corneal endothelium in this disease show a population of abnormal cells named 'ICE-cells'. In many patients some areas of the endothelium are occupied by ICE-cells and others by normal cells, an appearance described as 'subtotal-ICE'. Specular photomicroscopical observations suggest that ICE-cells and normal endothelial cells may actively interact at the boundary zone where they meet. The purpose of this study was to examine the ultrastructural appearances of the boundary zone to gain insight into the cellular pathology of this region. Thirty-five corneas taken from patients with the ICE syndrome were examined by light, transmission and scanning electron microscopy. The subtotal-ICE appearance was demonstrated in four specimens. The morphology of ICE-cells at the boundary zone suggests that they are non-motile but also implies a general state of high metabolic activity. Many of the normal endothelial cells in this region are damaged, an appearance which may result from a toxic effect from the nearby ICE-cells.
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Two corneal buttons were obtained from a patient with congenital hereditary endothelial dystrophy (CHED) at the ages of 2.5 years (right eye) and 14 years (left eye) and were studied by light and electron microscopy including immunogold labelling for collagen types I-V and laminin. The posterior collagenous layer (PCL) of Descemet's membrane contained collagen types I, III-V, and laminin: the latter was also localised to fine-banded and granular material in the posterior non-banded zone (PNBZ). Comparison of the endothelium 2.5 years and 14 years revealed occasional dystrophic changes in the former and extensive dystrophic changes in the latter. The distribution of collagen types I, III and V within the PCL supports previous morphological observations of fibroblast-like change of the endothelium in CHED. Persisting endothelial properties were manifest as positive labelling of type IV collagen and laminin. An excessive amount of laminin found in PNBZ and PCL is another stress-related endothelial reaction.
BACKGROUND: Granular corneal dystrophy is a rare indication for corneal transplantation. Both penetrating and lamellar keratoplasty have been recommended, but because granular corneal dystrophy is known to recur within the donor material and multiple grafts may be necessary, the best surgical option has not been clearly established. The cellular cause of the dystrophy is unknown and the authors hypothesized that the rate and pattern of recurrence within lamellar and penetrating grafts might give clues to its etiology. METHODS: The authors compared the visual outcome, rate, and pattern of recurrence after 20 penetrating keratoplasties and 11 lamellar keratoplasties for granular corneal dystrophy. RESULTS: Penetrating keratoplasty and lamellar keratoplasty have a good visual outcome in granular corneal dystrophy. Visual acuities after both procedures were not statistically different. Recurrence of the dystrophy within the graft material was almost universal within 4 years. It first appeared centrally and superficially, occasionally adopting a vortex pattern suggesting epithelial involvement. The recurrence-free interval was independent of size and type of graft performed. CONCLUSION: The authors recommend lamellar keratoplasty as a primary procedure in managing visually disabling granular corneal dystrophy if the deposits are limited to the superficial cornea. This is particularly applicable in younger patients in whom multiple procedures may be necessary over a lifetime due to recurrence of the dystrophy, and the lower morbidity rate associated with lamellar keratoplasty becomes appreciable. Although granular corneal dystrophy generally is classified as a stromal dystrophy, the pattern of recurrence is more consistent with an epithelial or tear-borne abnormality than a disease of the stromal keratocyte.
BACKGROUND: Posterior polymorphous dystrophy of the cornea is an uncommon, but well-recognized, congenital disease affecting Descemet's membrane and endothelium. Visual impairment usually is minimal and slowly progressive. Edema develops in a small number of patients, necessitating a corneal graft in middle age. An early manifestation of posterior polymorphous dystrophy with corneal edema present at birth or soon thereafter is extremely rare; only a few ultrastructural reports are available. METHODS: The corneal button of a 5-month-old baby with posterior polymorphous dystrophy was examined by conventional light and electron microscopy. FINDINGS: The anterior banded zone of Descemet's membrane was thinned (2 microns) in the axial part of the cornea, contained defects in the paraxial part, and was absent at the periphery. Where present, the anterior banded zone was lined posteriorly by a fibrocellular layer (containing fibroblast-like spindle cells and striated collagen fibrils) and a fibrillar layer forming an abnormal posterior collagenous layer. This layer was lined posteriorly by degenerate overlapping endothelial cells, which also were in apposition to the stroma in regions with an absent anterior banded zone. The defects in Descemet's membrane were used by the abnormal keratocytes to migrate between the anterior banded zone and the posterior collagenous layer. At the periphery, a multilayer of spindle cells was present behind the stroma. CONCLUSIONS: Failure to produce a continuous anterior banded zone indicates an onset of the disease before the twelfth week of gestation. It appears that, in posterior polymorphous dystrophy, there is a mosaic of better preserved and dystrophic endothelial cells and that the presence or absence of the normal components of Descemet's membrane is determined by the proportion of dystrophic cells in the endothelial cell population.
Trophozoites and cysts of 20 isolates of Acanthamoeba from the cornea and five from related samples were tested in vitro for sensitivity to ten drugs (three aromatic diamidines, two aminoglycosides, two macrolides, a polyene macrolide antibiotic, an organoarsenical and an antimetabolite) and two cationic antiseptics (chlorhexidine and polyhexamethylene biguanide, PHMB). Only chlorhexidine and PHMB showed uniform amoebacidal activity. Aromatic diamidines (pentamidine isethionate, propamidine isethionate and diminazene aceturate) generally proved effective against both forms of the amoeba; only pentamidine gave synergy with the biguanide while propamidine gave an additive effect. Other drugs tested proved erratic or ineffective against different isolates. Chlorhexidine alone, or together with propamidine, was subsequently used in two patients with proven Acanthamoeba keratitis; the causative isolates were sensitive to the individual compounds and to the combination in vitro. The treatment provided resolution of the clinical disease; amoebae were shown to be nonviable by histology and culture. The combination of chlorhexidine and propamidine is recommended for treatment of proven Acanthamoeba keratitis.
A corneal disc, obtained from a 52-year-old woman suffering from an early stage of the iridocorneal endothelial syndrome (ICE), was investigated by various morphological techniques to analyse the structural variations in the endothelial cells and to identify the collagen types within the abnormal layer of Descemet's membrane. Scanning electron microscopy of the posterior corneal surface revealed a mosaic of (a) flat hexagonal cells resembling irregular but normal endothelial cells, and (b) rounded hexagonal (ICE) cells with numerous surface microvilli. Degenerative changes were present in each cell type, but were more common in the flat hexagonal cells which contained intracytoplasmic spaces. By transmission electron microscopy the flat hexagonal cells exhibited many of the features of normal endothelial cells in terms of organelles and intercellular attachments, but lateral invaginations were absent. The ICE cells differed in that the apical surface was covered by microvilli and the cytoplasm contained tonofilaments, which were also observed by light microscopic immunocytochemical staining. Most commonly, intercellular attachments were rudimentary in both types of cell and intercellular spaces were dilated, but desmosomes were sometimes prominent in the ICE cells where interdigitations were pronounced. In some sectors, the basal surface of the ICE cells was indented by deposition of clumps of fibrillar collagenous material. An immunocytochemical study of the abnormal posterior deposits localised type IV collagen to the amorphous matrix and collagen types III and V, but not type I, to the collagen fibril bundles. Mononuclear inflammatory cells were identified between the ICE cells in the monolayer. The evidence suggests that some of the flat hexagonal cells were undergoing a degenerative change while others were transforming into ICE cells.
Posterior polymorphous corneal dystrophy (PPD) is a rare bilateral, autosomal-dominant disease. The presence of the epitheliumlike endothelium and the thickening of Descemet's membrane by the posterior collagenous layer (PCL) has been reported in the majority of published cases. Reepithelialization of the posterior cornea in donor tissue has been reported only once. Therefore, to examine this process we examined, by light and electron microscopy, three corneal buttons (an original and two subsequent keratoplasties after 3 and 4 years, respectively) from the left eye of a patient with bilateral disease. Our study showed a repopulation of the posterior surface of the donor corneas by the host epitheliumlike endothelium, which was of identical morphology in each case. In contrast to the previously published work, a posterior collagenous layer in the failed grafts was absent from the axial cornea, where the epitheliumlike endothelium was in direct contact with donor Descemet's membrane. A PCL at the periphery in the failed transplants was of the fibrocellular type and differed from the fibrillar PCL in the first keratoplasty specimen. The fibroblastlike cells within the fibrocellular PCL were distinct from the underlying epithelial-like cells and contained numerous tertiary phagolysosomes. We suggest that the major contributor to the fibrocellular PCL in the repeat keratoplasties was a fibrous ingrowth from the host/graft junction and not the epitheliumlike endothelium. It appears that the synthetic capacity of the epitheliumlike endothelium was similar to that of the normal epithelium and was much lower than that of normal native endothelium.
A prospective study of excimer laser photorefractive keratectomy was performed with the aim of correcting a range of myopic errors between -1.00 and -10.00 dioptres. Corneal healing was monitored through the first post-operative year by serial assessments of refraction, contrast sensitivity, corneal haze, pachymetry and keratometry. Eighty-one patients were recruited for the study. At 12 months 81% were within +/- 1.00 dioptre of desired emmetropia and with unaided vision of 6/12. Contrast sensitivity was found by Pelli-Robson assessment to be reduced throughout the 12 months and regression analysis predicted recovery by 2 years. At 12 months, however, only 15% of patients were found to have lost a single line of best corrected Snellen acuity. Predictability of results was found to be greatest for initial errors less than -4.00 dioptres. No serious complications were observed during the follow-up period, but refraction had not stabilised in all cases and patients remain under review.
In a retrospective survey of 117 operations for primary or recurrent pterygium, conjunctival autografting was compared with both excision without conjunctival closure ('bare sclera excision') and excision with complete conjunctival closure. The probability of corneal recurrence at 36 months after surgery was determined by survival curve analysis. In previously unoperated cases conjunctival autografting (n = 15) resulted in a 14% probability of recurrence, compared with 70% for bare sclera excision (n = 50) and 69% for excision with complete conjunctival closure (n = 20). In previously operated cases conjunctival autografting (n = 17) resulted in a 7% probability of recurrence, compared with 82% for bare sclera excision (n = 15). Hazard ratio analysis confirmed the statistical significance of these results at the 95% confidence level. Conjunctival autografting was more likely to produce an improvement in visual acuity than other forms of surgery.
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Published opinion supports the early use of prophylactic antibiotics soon after presentation of a potentially contaminated intraocular foreign body (IOFB) in the posterior segment, preferably within 12 hours of trauma when the visual acuity is still good. Recommended treatment includes topical, subconjunctival, parenteral and especially intravitreal antibiotic therapy to reduce the chance of endophthalmitis. Intravitreal therapy should include gentamicin with vancomycin or clindamycin to cover Bacillus spp., since this organism is responsible for half the endophthalmitis cases and produces beta-lactamase giving resistance to penicillins and cephalosporins. Intravitreal therapy is important because systemic and topical antibiotics do not penetrate the globe in sufficient concentration to control a fulminant infection associated with damaged tissue. Early therapy is essential, as delaying treatment until endophthalmitis occurs is less likely to save useful vision. All vitreous aspirated, plus pus if present, and the IOFB should be cultured for bacteria and fungi to identify pathogens and gain antibiotic sensitivities. The prevention of IOFB-associated endophthalmitis requires early recognition of the IOFB and enthusiastic antibiotic therapy at the time of its removal.
From a database of 1,122 penetrating keratoplasties performed under the care of the surgeons of the Corneal Clinic, Moorfields Eye Hospital (London, U.K.), 153 (14%) were identified as being complicated by postkeratoplasty glaucoma. The relative risk for its development varied with the indication for keratoplasty. Keratoconus had the lowest incidence along with some dystrophies, such as macular or granular dystrophy, and these were taken as the baseline for comparison. Anterior chamber dysgenesis syndromes had the highest risk among the indications for keratoplasty. Combined cataract or lens implant surgery was also found to be a risk factor, with anterior vitrectomy, anterior segment revision, and anterior chamber lens implant removal representing a greater risk than extracapsular extraction and posterior chamber lens implantation. Postkeratoplasty glaucoma was also strongly associated with peripheral anterior synechiae formation seen after keratoplasty.
A case is presented of a 49-year-old woman who has worn hard contact lenses for 26 years. Specular microscopy of the central corneal endothelium revealed marked bilateral polymegethism and a large coefficient of variation in cell size. Of greater significance was the presence of clumps of small cells. This may be related to the way the corneal endothelium responds to long-term anoxia.
The results of penetrating keratoplasty following trabeculectomy in 26 eyes where there was coexistent corneal disease and glaucoma are presented. Patients were aged 16-80 years at the time of drainage surgery (mean = 51 years) and there was a mean of 33.5 months between trabeculectomy and keratoplasty. The mean pressure fell from 35.3 mm Hg prior to trabeculectomy to 14.9 mm Hg at the time of keratoplasty and 20 mm Hg 12 months after keratoplasty. There was a 0.45 probability of maintaining normal intraocular pressure with medication at 5 years after keratoplasty; and a similar graft survival probability. The probability of maintaining both a clear graft and a normal pressure was only 0.27 at 5 years. In another 22 eyes combined trabeculectomy and penetrating keratoplasty was performed. Patients' ages ranged from 21-82 years (mean 55) at surgery, and 73% were aphakic. The intraocular pressure dropped from a mean of 28.9 mm Hg preoperatively to 14 mm Hg at 12 months. There was a 5 year probability of 0.7 of maintaining a clear graft but if both a clear graft and normal intraocular pressure are considered then the probability falls to 0.5 at 5 years. The hazard ratio for intraocular pressure control and graft survival between the two groups suggests that combined surgery may offer a better prognosis.