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PURPOSE: To examine the association of donor, recipient, and operative factors on graft dislocation after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS) as well as the effects of graft dislocation and elevated IOP on graft success and endothelial cell density (ECD) 3 years postoperatively. DESIGN: Cohort study within a multi-center, double-masked, randomized clinical trial. METHODS: 1,090 individuals (1,330 study eyes), median age 70 years, undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (6% of eyes). Recipient eyes receiving donor corneal tissue randomized by preservation time (PT) of 0-7 days (N=675) or 8-14 days (N=655) were monitored for early or late graft failure through 3 years. Donor, recipient, operative, and postoperative parameters were recorded including graft dislocation (GD), partial detachment, and pre- and post-operative IOP. Pre- and postoperative central donor ECD were determined by a central image analysis reading center. Proportional hazards, mixed effects, and logistic regression models estimated risk ratios and {99% confidence intervals}. RESULTS: Three independent predictive factors for GD were identified: a history of donor diabetes (odds ratio {OR}: 2.29 {1.30, 4.02}), increased pre-lamellar dissection central corneal thickness (OR: 1.13 {1.01, 1.27} per 25μ increase), and operative complications (OR: 2.97 {1.24, 7.11}). Among 104 (8%) eyes with GD, 30 (28.9%) developed primary donor or early failure and 5 (4.8%) developed late failure vs. 15 (1.2%; p

Bowman's layer corneal dystrophies (CDBs) include 2 distinct types: CDB1, or Reis-Bücklers (RBCD), and CDB2, or Thiel-Behnke (TBCD). We studied the genetic basis of 2 cases of apparent spontaneous CDB mutations and attempted to determine if these are sporadic and inheritable mutations.Retrospective molecular genetic study and case report.Twelve patients were recruited from 2 unrelated families for this study, including 2 affected individuals from one family (family A) and 1 affected individual from another (family B).Slit-lamp examination was performed for each patient to determine the disease phenotype. Histological analysis of affected cornea specimens was used for identification of pathogenic corneal opacities in 2 affected patients from family A.Genomic DNA was isolated from the blood samples and used for mutation screening of the TGFBI/BIGH3 gene. Sixteen polymorphic DNA markers from 9 different chromosomes were used to establish the maternity and paternity of the 2 probands.The 2 families were confirmed to be unrelated. The age onset of ocular symptoms was2 years for all 3 affected patients. Clinical diagnoses of CDB1 (RBCD) and CDB2 (TBCD) were made for probands A and B, respectively. The affected corneas showed epithelial haze with diffuse, irregular, patchy opacities in a honeycomb and geographic pattern. Subepithelial plaques, increased trichome staining of anterior stroma, and irregular Bowman's layer were observed. An R555Q mutation was found in TGFBI/BIGH3 in the 2 probands but not in their parents. The son of proband A was also affected and apparently inherited his disease allele from his father.The R555Q mutation occurred spontaneously and independently in the 2 unrelated CDB families and was confirmed to be transmitted to the next generation in 1 of the 2 families. These findings strongly support the notion that a genetic diagnosis should be determined for CDB and other dystrophies associated with mutations in TGFBI/BIGH3. The discovery of a spontaneous mutation should alert clinicians to be aware of the existence of genetic alterations for their patients without apparent family history of the disease.

Purpose To report 8 patients with misdiagnosis of MemoryLens intraocular lens (IOL) late postoperative calcification and the resulting potentially avoidable procedures leading to secondary complications. Design Retrospective interventional case series. Participants Eight patients with an opacified hydrophilic acrylic MemoryLens. Methods Eight cases of MemoryLens IOL opacification that were originally misdiagnosed were reviewed. The following parameters were noted: baseline patient characteristics, time frame of IOL opacification, original misdiagnosis, subsequent surgical procedures, and postexplantation outcomes and complications. Two explanted lenses from this series were available for laboratory analyses. They underwent gross and light microscopic evaluation and scanning electron microscopy with energy-dispersive x-ray spectroscopy (EDS). Main Outcome Measures Patient parameters noted above. The IOLs were examined for distribution, structure, and composition of the deposits causing opacification of their optic components. Results All 8 patients' IOLs were implanted between August 1999 and March 2000. Complaints of decreased visual function occurred 13 to 58 months after implantation. Half of the patients were initially diagnosed as having posterior capsular opacification and underwent neodymium:yttrium–aluminum–garnet laser capsulotomy. The other half were initially diagnosed with some form of vitreous involvement and underwent vitrectomies. Six of the 8 patients underwent subsequent lens exchanges, with 3 of them having postexchange complications including endophthalmitis, cystoid macular edema, and retinal detachment. Scanning electron microscopy with EDS confirmed the presence of calcified deposits on the surface of the 2 explants available for analysis. The deposits also stained positive for calcium. Conclusions Despite previous reports, misdiagnosis of MemoryLens IOL calcification leading to optic opacification still occurs. Not recognizing this process can lead to potentially avoidable surgical procedures and increased risk of complications after repeated interventions.

A murine model of heterotopic corneal transplantation has been developed. Whole corneas were removed from either inbred Balb/cJ or C57B1/6J mice and inserted into an abdominal subcutaneous pouch in C57B1/6J recipient mice. Fresh donor tissue, donor corneas cultured at 37°C in 5 per cent CO2-95 per cent room air, or donor corneas cultured at 37°C in two atmospheres of 98 per cent 02 - 2 per cent CO2 (hyperbaric oxygen) were utilized. Twenty-one days later, the recipients were sacrificed and the heterotopic grafts were examined in a masked fashion. Rejected grafts were edematous, opaque, and vascularized. In contast, unrejected grafts were clear and nonvascularized. These results were further confirmed by histological examination of the donor grafts in a masked fashion. Control syngeneic grafts were not rejected. The fresh allografts were usually rejected (91%) as were the allografts cultured in CO2 - room air (90%). Thus, this murine model of heterotopic corneal transplantation appears to be useful for the...

Lacrimal tissue and accessory lacrimal tissue from seven autopsy cases, lacrimal tissue from three patients undergoing orbital exploration, and biopsy specimens from conjunctiva of 14 subjects were examined for the presence and distribution of secretory component by three anti-secretory-component antisera. Secretory component was present in all lacrimal and accessory lacrimal tissues but in no other ocular tissues. Over 60% of acinar cells stained for secretory component; about 5% of acinar cells stained brightly; about 30% of tubular cells stained brightly. Main and accessory lacrimal tissues appeared identical in their staining patterns. We concluded that the main sites of synthesis of secretory IgA in human ocular tissues are the lacrimal and accessory lacrimal tissues.

The ocular surface represents an immunologic microcosm in which certain local immunologic and paraimmunologic defense systems analogous or identical to those of other mucosal surfaces are operative. These defenses include a resident normal flora; intrinsic anatomic barriers; secretion of mucous and certain chemical bacteriostatics and bacteriolytics; local humoral (slgA) antibody secretion; and local T-lymphocyte cellular responses. A series of sophisticated mechanisms has evolved to defend the ocular surface against diverse environmental pathogens. Often, the activation of one system leads to the subsequent activation of another, providing a highly integrated, series of mechanisms for host defense. And, it is clear that close integration of these various mechanisms provides a highly efficient amplification system for host defense, so that when one mechanism fails to deal with the invading pathogen the next mechanism is then efficiently initiated. Only in those situations where the pathogen overwhelms these defense systems, or is of such a persistent nature that it becomes resistant to removal by these various mechanisms, or alternatively is able to subvert its identity and, therefore, evade these mechanisms do organisms infect and cause disease. It is undoubtedly the complex interaction of all of these defense systems, both paraimmunologic and immunologic, which finally determines the integrity of the ocular surface.

Recent evidence has been collected by several investigators defining a distinct population of dendritic cells (Langerhans cells) of mesenchymal origin residing in the epidermal surfaces of many mammalian species. These cells play a dominant role in the processing of antigens presented through cutaneous surfaces and carry a Class II histocompatability antigen felt to be of central importance in the afferent arm of allograft rejection. They also possess many of the characteristics of macrophages active in the efferent arm of immunologic responses. An equivalent subset of dendritic cells (Langerhans cells) in ocular surface epithelium of the human, mouse rat, and guinea pig has been identified by enzyme histochemistry, immunofluorescence, and electron microscopy. Ocular surface Langerhans cells proliferate in the setting of corneal inflammation (remote and recent) and are depleted by topical and systemic corticosteroids. Ocular surface Langerhans cells may play a central role in ocular contact hypersensitivity, corneal allograft rejection, and ocular surface immune surveillance.

Main and accessory lacrimal tissues from autopsy and biopsy specimens were compared histologically and immunohistologically. Formaldehyde-fixed, paraffin-embedded specimens were studied by light microscopy with hematoxylinand-eosin and PAS staining. Glutaraldehyde-fixed, Epon-embedded specimens were sectioned at 1 micron, stained with alkaline Giemsa, and studied by light microscopy. Specimens fixed in a solution of alcohol and acetic acid were stained by immunofluorescence techniques for lactoferrin, lysozyme, secretory component, and the immunoglobulins IgG, IgA, IgM, IgD, and IgE. The main and the accessory lacrimal tissues were identical histologically and had identical distributions of secretory products and immunoglobulin-containing plasma cells. The finding of myoepithelial cells in 1-micron sections of accessory lacrimal tissue indicates autonomic innervation in that tissue. This finding, in conjunction with the identical immunohistology, indicates a common source for unstimulated and stimulated tears.

The main lacrimal gland and accessory lacrimal tissue from seven autopsy cases, lacrimal biopsy specimens from three patients, and conjunctival biopsy specimens from ten patients were examined for lactoferrin by an immunohistologic technique. Lactoferrin was identified and localized to acinar epithelial cells of both main and accessory lacrimal tissue. Lactoferrin was not found in conjunctival tissue except within conjunctival neutrophils. Other possible sources of human tear lactoferrin were considered, but we concluded from our data that the primary source of lactoferrin in normal human tears is the acinar epithelium of the main and accessory lacrimal glands.

• Possible local sources of human tear lysozyme were investigated using an indirect immunofluorescence technique. Lysozyme was identified in 20% to 50% of acinar and ductular epithelial cells of both main and accessory lacrimal glands. The staining was granular in character and confined to the apices of the cells. Cells that stained positive tended to be grouped. Interstitial tissues of main and accessory lacrimal tissues did not stain. Conjunctiva and all other ocular tissues examined were unstained by antilysozyme antisera. Our findings are compatible with lysozyme either being produced in lacrimal tissue or being concentrated from plasma. The absence of any other lysozyme-specific fluorescence in the interstitial elements of the lacrimal tissues supports the notion of local synthesis by acinar lacrimal tissue.

A 35-year-old woman who had undergone bilateral penetrating corneal grafts for keratoconus had keratoconus in the eye that had received a graft 16 years earlier. A second penetrating keratoplasty was performed, and the excised button was examined with light and electron microscopy. Both the light and electron microscopic findings were consistent with the clinical diagnosis of keratoconus. Keratoconus in a graft for the same disease should be added to the list of late complications of successful keratoplasties.

We describe a simple and reliable technique for the preparation of corneal epithelial flat mounts. The technique is based on incubation of corneas or whole globes in an EDTA solution prior to fixation. Corneal epithelial flat mounts prepared by this technique are suitable for study by immunofluorescence or enzyme histochemistry.