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Purpose: The International Committee for the Classification of Corneal Dystrophies (IC3D) was created in 2005 to develop a new classification system integrating current information on phenotype, histopathology, and genetic analysis. This update is the third edition of the IC3D nomenclature., Methods: Peer-reviewed publications from 2014 to 2023 were evaluated. The new information was used to update the anatomic classification and each of the 22 standardized templates including the level of evidence for being a corneal dystrophy [from category 1 (most evidence) to category 4 (least evidence)]., Results: Epithelial recurrent erosion dystrophies now include epithelial recurrent erosion dystrophy, category 1 ( COL17A1 mutations, chromosome 10). Signs and symptoms are similar to Franceschetti corneal dystrophy, dystrophia Smolandiensis, and dystrophia Helsinglandica, category 4. Lisch epithelial corneal dystrophy, previously reported as X-linked, has been discovered to be autosomal dominant ( MCOLN1 mutations, chromosome 19). Classic lattice corneal dystrophy (LCD) results from TGFBI R124C mutation. The LCD variant group has over 80 dystrophies with non-R124C TGFBI mutations, amyloid deposition, and often similar phenotypes to classic LCD. We propose a new nomenclature for specific LCD pathogenic variants by appending the mutation using 1-letter amino acid abbreviations to LCD. Pre-Descemet corneal dystrophies include category 1, autosomal dominant, punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD) ( PRDX3 mutations, chromosome 10). Typically asymptomatic, it can be distinguished phenotypically from pre-Descemet corneal dystrophy, category 4. We include a corneal dystrophy management table., Conclusions: The IC3D third edition provides a current summary of corneal dystrophy information. The article is available online at https://corneasociety.org/publications/ic3d ., Competing Interests: The other authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The aim of this study was to determine anterior segment optical coherence tomography angiography (AS-OCTA) parameters to assess ocular redness severity., Methods: AS-OCTA analyses of 60 eyes of 40 patients were grouped according to ocular redness stages using the 5-category validated bulbar redness scale in a cross-sectional retrospective study (groups 1-5). A subset of patients with slit-lamp photographs, total 35 eyes of 23 patients, were assessed with 10-category validated bulbar redness scale for comparison. AS-OCTA images of nasal and temporal bulbar conjunctiva were analyzed. Vessel density (VD) represented the blood flow pixels by the total pixels of image (%); vessel diameter index represented the VD by the skeletonized density; fractal dimension, measured with the box-count method, represented the vessel branching complexity. Averaged nasal and temporal parameters for each eye were correlated to validated bulbar redness scales., Results: There was no statistical difference between groups for age ( P = 0.118), sex ( P = 0.501), eye laterality (OD/OS; P = 0.111), or location (nasal/temporal; P = 0.932). In the 5-category scale, VD significantly increased from group 1 to 2 (31.5 ± 1.9% and 33.4 ± 2.2%, P = 0.023), 2 to 3 (36.0 ± 3.5%, P < 0.001), and 4 to 5 (40.2 ± 2.9 and 46.5 ± 2.8, P < 0.001). The correlations were 0.805 ( P < 0.001) and 0.893 ( P < 0.001) for the 5-category and 10-category scales, respectively. Vessel diameter index showed a significant increase from 1 to 2 (2.90 ± 0.17 and 3.00 ± 0.15; P = 0.004) and 4 to 5 (2.92 ± 0.31 and 3.33 ± 0.08; P = 0.001). The correlations were 0.550 ( P < 0.001) and 0.625 ( P < 0.001) for the respective scales. The fractal dimension showed no significant differences between subsequent groups. The correlations were 0.445 ( P < 0.001) and 0.583 ( P < 0.001), respectively., Conclusions: Conjunctival AS-OCTA VD was the most reliable parameter to assess ocular redness., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Following identification of limbal stem cells, efforts have been devoted to restore and/or replace these essential progenitors of the corneal epithelium. Limbal stem cell deficiency, commonly a consequence of ocular chemical injury, results in clinically compromised vision consequent to corneal conjunctivalization. The insight of Kim and Tseng provided experimental proof of the concept that even in the presence of total limbal stem cell deficiency, amnion membrane overlay grafts can promote limbal recovery as a means of ocular surface reconstruction., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this report was to describe 4 cases of acute corneal transplant rejection occurring in association with coronavirus disease 2019 (COVID-19) mRNA vaccination., Methods: Four patients with prior keratoplasty developed presumed immunologic rejection after the mRNA-1273 vaccination for coronavirus 2 (SARS-CoV-2). Case 1 had received Descemet membrane endothelial keratoplasty 6 months ago and presented with endothelial graft rejection 3 weeks after the first vaccine dose. Case 2 had undergone penetrating keratoplasty 3 years previously and presented with acute endothelial rejection 9 days after the second vaccine dose. Case 3 had prior Descemet stripping automated endothelial keratoplasty (DSAEK) and began experiencing symptoms of endothelial graft rejection 2 weeks after the second vaccine dose. Case 4 presented with endothelial rejection of the penetrating keratoplasty graft 2 weeks after the second vaccine dose., Results: Frequent topical corticosteroids alone were initiated in all 4 cases. In case 1, the endothelial rejection line appeared fainter with improvement in visual acuity and corneal edema 5 weeks after diagnosis. Case 2 experienced complete resolution of corneal stromal edema and rejection line 6 weeks after diagnosis. Cases 3 and 4 have both experienced initial improvement with steroid treatment as well., Conclusions: These cases suggest acute corneal endothelial rejection may occur soon after either dose of the COVID-19 mRNA vaccine. Prompt initiation of aggressive topical steroid therapy may result in complete resolution of clinical signs and symptoms. Further studies are needed to elucidate the causal mechanism of corneal graft rejection after COVID-19 vaccination., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To evaluate the efficacy and safety of a hinged pupil expansion device (PED) in eyes with small pupils undergoing phacoemulsification., Methods: In this prospective, multicenter, interventional case series of 57 eyes with suboptimal pharmacologic pupil dilation (<5 mm diameter), a hinged PED (I-Ring, Beaver-Visitec International, Waltham, MA) was applied to facilitate surgical visualization during cataract surgery. The pupil diameters (PD) were measured at different stages of the procedure and at the 1-month follow-up visit. Rate of successful intraoperative PED deployment, pupil size, and shape were assessed., Results: The mean patient age was 70.5 ± 12.1 years. The I-Ring PED was successfully applied in all eyes. The mean PD at various stages were 4.1 ± 1.1 mm (dilation with eye drops only preoperatively), 4.3 ± 1.1 mm (dilation after intracameral epinephrine and ophthalmic viscoelastic device), 6.80 ± 0.00 mm (with PED applied), and 5.7 ± 1.1 mm (end of surgery). A statistically significant difference (P < 0.001) was observed between the mean PD with intracameral medications and with PED application. Postoperative circular pupil was observed in 54 of 57 eyes (94.7%) and the mean eccentricity index (n = 57 eyes) was 0.11 ± 0.22. No significant adverse events were observed., Conclusion: The I-Ring PED safely and effectively provided and maintained adequate pupil expansion and surgical visualization in eyes with small pupils undergoing cataract surgery. Postoperatively 95% of eyes attained circular pupils. This hinged PED is an additional instrumentation option for the safe and effective expansion of inadequately sized pupils during cataract surgery., Competing Interests: None

Purpose: Assessment of anterior segment-optical coherence tomography angiography (AS-OCTA) to determine severity of corneal neovascularization (CoNV)., Design: Retrospective, cross-sectional, single-center study., Methods: Patients of various CoNV etiologies were selected and classified into mild, moderate, and severe. Their AS-OCTA images were measured for CoNV anterior limit, CoNV posterior limit, CoNV thickness, CoNV depth%, CoNV vessel density, CoNV area, and CoNV volume. Further, AS-OCTA parameters were correlated to clinical parameters, such as classification, a numerical severity scale, vascular clock hours, and best-corrected visual acuity (BCVA)., Results: A total of 19 mild, 10 moderate, and 6 severe CoNV eyes were included with no significant age-gender differences. CoNV depth% and volume increased from mild to moderate (9.3 ± 1.1% to 17.7 ± 3.3%, P = .030, and 0.2 ± 0.1 mm 3 to 1.0 ± 0.3 mm 3 , P = .025, respectively) and from moderate to severe CoNV (44.6 ± 5.3%, P < .001, and 2.0 ± 0.3 mm 3 , P = .014, respectively). CoNV area and posterior limit increased from mild to moderate (1.7 ± 0.3 mm 2 to 4.6 ± 0.7 mm 2 , P = .001, and 217.7 ± 16.8 μm to 349.1 ± 54.9 μm, P = .048, respectively), not from moderate to severe (P = .999 and P = .403, respectively). CoNV thickness increased from moderate to severe (218.2 ± 46.6 μm to 340.2 ± 8.7 μm, P = .020), but not from mild to moderate. CoNV area and volume showed good correlations to CoNV staging (r = 0.703 and r = 0.771, respectively; P < .001) and severity scale (r = 0.794 and r = 0.712, respectively; P < .001). CoNV area showed good correlation to clock hours (r = 0.749, P < .001). CoNV depth and volume showed good correlation to BCVA (r = 0.744 and r = 0.722, respectively; P < .001). CoNV anterior limit and vessel density showed no significant correlations (P ≥ .05)., Conclusions: Severe CoNV shows greater CoNV posterior limit, thickness, depth%, area, and volume on AS-OCTA compared to mild. CoNV volume and depth strongly correlate to BCVA. AS-OCTA provides novel, quantitative, and noninvasive parameters for assessing CoNV severity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Diabetes mellitus is a disease caused by innate or acquired insulin deficiency, resulting in altered glucose metabolism and high blood glucose levels. Chronic hyperglycemia is linked to development of several ocular pathologies affecting the anterior segment, including diabetic corneal neuropathy and keratopathy, neovascular glaucoma, edema, and cataracts leading to significant visual defects. Due to increasing disease prevalence, related medical care costs, and visual impairment resulting from diabetes, a need has arisen to devise alternative systems to study molecular mechanisms involved in disease onset and progression. In our current study, we applied a novel 3D in vitro model of the human cornea comprising of epithelial, stromal, and neuronal components cultured in silk scaffolds to study the pathological effects of hyperglycemia on development of diabetic corneal neuropathy. Specifically, exposure to sustained levels of high glucose, ranging from 35 mM to 45 mM, were applied to determine concentration-dependent effects on nerve morphology, length and density of axons, and expression of metabolic enzymes involved in glucose metabolism. By comparing these metrics to in vivo studies, we have developed a functional 3D in vitro model for diabetic corneal neuropathy as a means to investigate corneal pathophysiology resulting from prolonged exposure to hyperglycemia.

Purpose: To propose a new treatment paradigm for chemical burns to the eye - in the acute and chronic phases., Methods: Recent laboratory and clinical data on the biology and treatment of chemical burns are analyzed., Results: Corneal blindness from chemical burns can now be successfully treated with a keratoprosthesis, on immediate and intermediate bases. Long term outcomes, however, are hampered by early retinal damage causing glaucoma. New data suggest that rapid diffusion of inflammatory cytokines posteriorly (TNF-α, etc) can severely damage the ganglion cells. Prompt anti-TNF-α treatment is markedly neuroprotective. Long term profound reduction of the intraocular pressure is also vital., Conclusion: A new regimen, in addition to standard treatment, for severe chemical burns is proposed. This involves tumor necrosis factor alpha (TNF-α) inhibition promptly after the accident (primarily for retinal neuroprotection), prophylactic maximal lowering of the intraocular pressure (starting immediately), and keratoprosthesis implantation in a later quiet state.

Purpose: Galectin-3 is a carbohydrate-binding protein known to promote expression of matrix metalloproteinases, a hallmark of ulceration, through interaction with the extracellular matrix metalloproteinase inducer CD147. The aim of this study was to investigate the distribution of galectin-3 in corneas of patients with ulcerative keratitis and to determine its relationship to CD147 and the presence of gelatinolytic activity., Methods: This was an observational case series involving donor tissue from 13 patients with active corneal ulceration and 6 control corneas. Fixed-frozen sections of the corneas were processed to localize galectin-3 and CD147 by immunofluorescence microscopy. Gelatinolytic activity was detected by in situ zymography., Results: Tissue from patients with active corneal ulceration showed a greater galectin-3 immunoreactivity in basal epithelia and stroma compared with controls. Immunofluorescence grading scores revealed increased colocalization of galectin-3 and CD147 in corneal ulcers at the epithelial-stromal junction and within fibroblasts. Quantitative analysis using the Manders' colocalization coefficient demonstrated significant overlap in corneas from patients with ulcerative keratitis (M1 = 0.29; M2 = 0.22) as opposed to control corneas (M1 = 0.01, P < 0.01; M2 = 0.02, P < 0.05). In these experiments, there was a significant positive correlation between the degree of galectin-3 and CD147 colocalization and the presence of gelatinolytic activity., Conclusions: Our results indicate that concomitant stimulation and colocalization of galectin-3 with CD147 are associated with increased gelatinolytic activity in the actively ulcerating human cornea and suggest a mechanism by which galectin-3 may contribute to the degradation of extracellular matrix proteins during ulceration.

Purpose: To compare aqueous humor concentrations of topically applied moxifloxacin 0.5% ophthalmic solution alone or in combination with dexamethasone 0.1% and to correlate these concentrations with the minimum inhibitory concentrations (MICs) for common endophthalmitis-causing organisms., Methods: Sixty-eight patients undergoing routine phacoemulsification with intraocular lens implantation received either moxifloxacin 0.5% alone or moxifloxacin 0.5% combined with dexamethasone. For both groups, 1 drop of the test solution was instilled 4 times daily 1 day preoperatively and 1 drop 1 h preoperatively. An aqueous humor sample obtained immediately before paracentesis was submitted to high-performance liquid chromatography-tandem mass spectrometry to determine the moxifloxacin concentration., Results: The mean concentrations of moxifloxacin were 986.6 ng/mL in the moxifloxacin with dexamethasone group and 741.3 ng/mL in the moxifloxacin group (P = 0.13). Moxifloxacin concentrations of all samples exceeded the MICs for Staphylococcus epidermidis, S. aureus, and Streptococcus pneumoniae. All samples in the moxifloxacin with dexamethasone group and 94% in the moxifloxacin group achieved the MIC for Enterococcus species. For quinolone-resistant S. aureus, the MIC was achieved in 29% in the moxifloxacin with dexamethasone group and 9% in the moxifloxacin group (P = 0.06)., Conclusion: Aqueous humor moxifloxacin concentrations were higher when topically administrated in combination with dexamethasone compared to the moxifloxacin alone. However, this difference was not statistically significant. Nevertheless, the MICs of the most common pathogens associated with endophthalmitis were exceeded in both study groups.

Purpose: Although members of the galectin family of carbohydrate-binding proteins are thought to play a role in the immune response and regulation of allograft survival, little is known about the galectin expression signature in failed corneal grafts. The aim of this study was to compare the galectin expression pattern in accepted and rejected murine corneal allografts., Methods: Using BALB/c mice as recipients and C57BL/6 mice as donors, a total of 57 transplants were successfully performed. One week after transplantation, the grafts were scored for opacity by slit-lamp microscopy. Opacity scores of 3+ or greater on postoperative week 4 were considered rejected. Grafted corneas were harvested on postoperative week 4, and their galectin expressions were analyzed by Western blot and immunofluorescence staining., Results: As determined by the Western blot analyses, galectins-1, 3, 7, 8 and 9 were expressed in normal corneas. Although in both accepted and rejected grafts, expression levels of the 5 lectins were upregulated compared with normal corneas, there were distinct differences in the expression levels of galectins-8 and 9 between accepted and rejected grafts, as both the Western blot and immunofluorescence staining revealed that galectin-8 is upregulated, whereas galectin-9 is downregulated in the rejected grafts compared with the accepted grafts., Conclusions: Our findings that corneal allograft rejection is associated with increased galectin-8 expression and reduced galectin-9 expression, support the hypothesis that galectin-8 may reduce graft survival, whereas galectin-9 may promote graft survival. As a potential therapeutic intervention, inhibition of galectin-8 and/or treatment with exogenous galectin-9 may enhance corneal allograft survival rates.

Purpose: To update the 2008 International Classification of Corneal Dystrophies (IC3D) incorporating new clinical, histopathologic, and genetic information., Methods: The IC3D reviewed worldwide peer-reviewed articles for new information on corneal dystrophies published between 2008 and 2014. Using this information, corneal dystrophy templates and anatomic classification were updated. New clinical, histopathologic, and confocal photographs were added., Results: On the basis of revisiting the cellular origin of corneal dystrophy, a modified anatomic classification is proposed consisting of (1) epithelial and subepithelial dystrophies, (2) epithelial-stromal TGFBI dystrophies, (3) stromal dystrophies, and (4) endothelial dystrophies. Most of the dystrophy templates are updated. The entity "Epithelial recurrent erosion dystrophies" actually includes a number of potentially distinct epithelial dystrophies (Franceschetti corneal dystrophy, Dystrophia Smolandiensis, and Dystrophia Helsinglandica) but must be differentiated from dystrophies such as TGFBI-induced dystrophies, which are also often associated with recurrent epithelial erosions. The chromosome locus of Thiel-Behnke corneal dystrophy is only located on 5q31. The entity previously designated as a variant of Thiel-Behnke corneal dystrophy on chromosome 10q24 may represent a novel corneal dystrophy. Congenital hereditary endothelial dystrophy (CHED, formerly CHED2) is most likely only an autosomal recessive disorder. The so-called autosomal dominant inherited CHED (formerly CHED1) is insufficiently distinct to continue to be considered a unique corneal dystrophy. On review of almost all of the published cases, the description appeared most similar to a type of posterior polymorphous corneal dystrophy linked to the same chromosome 20 locus (PPCD1). Confocal microscopy also has emerged as a helpful tool to reveal in vivo features of several corneal dystrophies that previously required histopathologic examination to definitively diagnose., Conclusions: This revision of the IC3D classification includes an updated anatomic classification of corneal dystrophies more accurately classifying TGFBI dystrophies that affect multiple layers rather than are confined to one corneal layer. Typical histopathologic and confocal images have been added to the corneal dystrophy templates.

Purpose: The aim of this study was to assess the effect of donor and recipient factors on corneal allograft rejection and evaluate whether a rejection event was associated with graft failure., Methods: One thousand ninety subjects undergoing penetrating keratoplasty for a moderate risk condition (principally Fuchs dystrophy or pseudophakic corneal edema) were followed for up to 12 years. Associations of baseline recipient and donor factors with the occurrence of a rejection event were assessed in univariate and multivariate proportional hazards models., Results: Among 651 eyes with a surviving graft at 5 years, the 10-year graft failure (±99% confidence interval) rates were 12% ± 4% among eyes with no rejection events in the first 5 years, 17% ± 12% in eyes with at least 1 probable, but no definite rejection event, and 22% ± 20% in eyes with at least 1 definite rejection event. The only baseline factor significantly associated with a higher risk of definite graft rejection was a preoperative history of glaucoma, particularly when previous glaucoma surgery had been performed and glaucoma medications were being used at the time of transplant (10-year incidence 35% ± 23% compared with 14% ± 4% in eyes with no history of glaucoma/intraocular pressure treatment, P = 0.008)., Conclusions: Patients who experienced a definite rejection event frequently developed graft failure raising important questions as to how we might change acute and long-term corneal graft management. Multivariate analysis indicated that previous use of glaucoma medications and glaucoma filtering surgery was a significant risk factor related to a definite rejection event.

Purpose: To compare the anatomic and refractive outcomes in eyes having phacoemulsification with 1 of 3 clear corneal incision (CCI) closure methods., Setting: Ambulatory surgical center, Makati, Philippines., Design: Prospective randomized clinical trial., Methods: Patients having phacoemulsification cataract surgery had wound closure using no additional treatment (control), a single 10-0 nylon suture, or a liquid adhesive ocular bandage (Ocuseal). The main outcome measures were wound-edge closure rates, surgically induced astigmatism (SIA), foreign-body sensation, and intraocular pressure (IOP) 1, 3, 5, 7, and 14 days postoperatively., Results: The study evaluated 90 eyes. There was a significant improvement in wound-edge closure rates in the suture group and the ocular bandage group compared with the control group (P<.001). A significant increase in SIA occurred in the sutured group but not in the control or ocular bandage groups (P<.001). The ocular bandage group had significantly less foreign-body sensation than the control and suture groups (P<.001). There were no significant differences in IOP between the groups (P=.515)., Conclusions: The liquid adhesive ocular bandage resulted in improved wound-edge closure, reduced SIA, and diminished foreign-body sensation. Suturing was associated with improved wound-edge closure but increased SIA and foreign-body sensation. Unsutured incisions led to delayed wound-edge closure and increased foreign-body sensation., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe a case of conjunctival malignant melanoma (MM) arising from primary acquired melanosis in a patient with neurofibromatosis type 1 (NF-1)., Methods: Case report and literature review., Results: A 66-year-old woman with a history of NF-1 presented with extensive pigmentation of the left bulbar conjunctiva. Conjunctival biopsies demonstrated MM arising from primary acquired melanosis with atypia. Two excision and cryotherapy procedures did not completely eradicate the conjunctival pigment, which was then treated with topical mitomycin C. Subsequent biopsies and clinical examinations have revealed no remaining tumor., Conclusion: Conjunctival MM is uncommon in patients with NF-1 and can be successfully treated with excision, cryotherapy, and topical mitomycin C.

Purpose: To evaluate whether adding perioperative topical ketorolac tromethamine 0.4% improves cataract surgery outcomes relative to topical steroids alone in patients without known risk factors for cystoid macular edema (CME)., Design: Prospective, randomized, investigator-masked, multicenter clinical trial., Methods: Patients scheduled to undergo phacoemulsification and with no recognized CME risks (diabetic retinopathy, retinal vascular disease, or macular abnormality) were randomized to receive either prednisolone acetate 1% 4 times daily (QID) alone (steroid group; n = 278) or prednisolone 1% QID plus ketorolac 0.4% QID (ketorolac/steroid group; n = 268) for approximately four weeks postoperatively. In the ketorolac/steroid group, patients also received topical ketorolac 0.4% QID for three days preoperatively. In both groups, patients received four doses of ketorolac 0.4% one hour before surgery. Patients with capsular disruption or vitreous loss intraoperatively were exited from the study. Outcome measures included CME incidence, retinal thickness as measured by optical coherence tomography (OCT), best-corrected visual acuity, and contrast sensitivity., Results: No patients in the ketorolac/steroid group and five patients in the steroid group had clinically apparent CME (P = .032). Based on OCT, no ketorolac/steroid patient had definite or probable CME, compared with six steroid patients (2.4%; P = .018). In the ketorolac/steroid group, mean retinal thickening was less (3.9 microm vs 9.6 microm; P = .003), and fewer patients had retinal thickening of more than 10 microm as compared with the steroid group (26% vs 51%; P < .001)., Conclusions: This study suggests that adding perioperative ketorolac to postoperative prednisolone significantly reduces the incidences of CME and macular thickening in cataract surgery patients already at low risk for this condition.

Background: To perform lamellar keratolimbal allograft transplantation in a one-step procedure with a single graft, we investigated the feasibility of harvesting eccentric lamellar keratolimbal grafts from conventionally processed corneoscleral buttons using a manually guided microkeratome in conjunction with an artificial anterior chamber system., Methods: We used the Moria LSK-One microkeratome and the automated lamellar therapeutic keratoplasty (ALTK) system (Antony, France). Ten human donor eyes were used to obtain single-piece lamellar keratolimbal grafts. Specimens were processed for light and electron microscopy., Results: Eccentric keratolimbal grafts could be obtained from all human donor buttons. Grafts include a crescent-shaped limbal and a large corneal portion. No visible damage to the limbal region was discernible., Conclusion: Our data show that the LSK-One microkeratome in conjunction with the ALTK system allows harvesting eccentric keratolimbal grafts from donor corneoscleral buttons.

Purpose: The Cornea Donor Study was designed to investigate the safety and efficacy of older donor corneal tissue compared with younger donor tissue in recipient eyes at moderate risk to the graft from progressive endothelial failure. Baseline patient data, including indications for transplant, intraoperative complication rates, and early postoperative complication rates are described herein., Methods: This study was a multicenter prospective, double-masked, controlled clinical trial., Results: Fuchs dystrophy was the most common indication for corneal transplantation (61%). Intraoperative complications occurred in 33 (3%) patients. A persistent epithelial defect was the most commonly reported postoperative complication, occurring in 92 patients (8%)., Conclusion: Intraoperative and postoperative complication rates were low. There was no apparent association between donor or recipient age and either intraoperative or early postoperative complication rates.

Purpose: To evaluate the safety and efficacy of laser in situ keratomileusis (LASIK) to enhance refractive status following other corneal surgical procedures., Setting: Clinical office-based practice., Methods: Seventy-one eyes of 57 patients had LASIK for refractive errors following radial keratotomy (n = 22), astigmatic keratotomy (n = 13), photorefractive keratectomy (n = 18), and penetrating keratoplasty (n = 18). A Moria LSK-1 microkeratome was used with a Visx S2 or Wavelight Allegretto excimer laser. Data were acquired by retrospective chart review of all appropriately qualified patients., Results: The mean preoperative manifest refractive spherical equivalent (MRSE) was -3.93 diopters (D) +/- 2.83 (SD) in myopic eyes and +1.43 +/- 1.79 D in hyperopic eyes. The mean time from the initial corneal surgical procedure to LASIK was 65.0 months. The mean post-LASIK follow-up was 9.40 months (range 1 to 42 months). Postoperatively, the mean MRSE was -0.85 +/- 1.42 D in myopic eyes (P<.0001) and -0.16 +/- 1.09 D in hyperopic eyes (P<.0001). Enhancement by LASIK was required in 14% of eyes., Conclusion: In eyes that have had a variety of previous corneal surgeries, LASIK offers a safe and predictable method for enhancing refractive results.

Purpose: Because the lipid layer of the tear film is recognized as a critical component in dry eye disease, this study was designed to determine if a single eye drop of either Soothe or Systane produces a significant increase in lipid layer thickness (LLT) for subjects reporting symptoms indicative of dry eyes., Methods: A double-blind, internally paired study was performed. A custom-built lipid layer interferometer, enabling characterization of lipid layer interference patterns, was used to quantify baseline LLT (OU) of eligible subjects. Inclusion criteria included: 1) presence of dry eye symptoms and 2) baseline LLT < or =75 nm. Subjects (n = 40) received a single eye drop of Soothe in one eye and a single eye drop of Systane in the contralateral eye. After the instillation of each test drop, LLT was reanalyzed for all subjects., Results: The mean +/- standard error baseline LLT pre-eye drop instillation was 60.0 +/- 1.8 nm for eyes treated with Soothe and 61.5 +/- 1.8 nm for eyes treated with Systane. These means were not significantly different (p > 0.5). The mean LLT for eyes treated with Soothe increased to 124.4 +/- 4.9 nm (p < 0.0001). The mean LLT for eyes treated with Systane increased to 71.3 +/- 2.6 nm (p < 0.0001). The LLT increase from Soothe was significantly greater than that from Systane (p < 0.0001)., Conclusions: In subjects with symptoms indicative of dry eye states and LLT < or =75 nm, one eye drop of Soothe more than doubled LLT, a 107% mean increase, whereas Systane increased LLT by 16%.

Objective: Keratitis-ichthyosis-deafness (KID) syndrome is a rare congenital ectodermal dysplasia characterized by the association of hyperkeratotic skin lesions, moderate to profound sensorineural hearing loss and vascularizing keratitis. Mutations in the GJB2 gene coding for connexin 26, a component of gap junctions in epithelial cells, have been observed in several KID patients. Variable ocular manifestations of the disease in 3 patients with molecular genetically confirmed KID syndrome are reported., Design: Retrospective case series., Methods: Clinical examination and molecular genetic analysis for mutations in the GJB2 gene were performed in 3 patients with KID syndrome ages 5, 13, and 41 years., Results: Visual acuity ranged from normal to severe visual loss. The ocular signs included loss of eyebrows and lashes, thickened and keratinized lids, trichiasis, recurrent corneal epithelial defects, superficial and deep corneal stromal vascularization with scarring, keratoconjunctivitis sicca, and, in one patient, presumed limbal insufficiency. Whereas ocular surface integrity could be maintained with artificial tears in one patient, and an epithelial defect healed under conservative treatment in the second patient, multiple surgical procedures including superficial keratectomies, limbal allograft transplantation with systemic immunosuppression, amniotic membrane transplantation, lateral tarsorrhaphies, and lamellar keratoplasty could not preserve useful vision in the third patient., Conclusions: KID syndrome may affect the ocular adnexae and surface with variable severity independent of the age of the patient. Lid abnormalities, corneal surface instability, limbal stem cell deficiency with resulting corneal complications, and dry eye are the main ocular manifestations.

Purpose: To assess the clinical characteristics, incidence, and pathologic correlation of corneal epithelial adhesion abnormalities encountered during LASIK., Design: Prospective noncomparative interventional case series., Participants: Five hundred consecutive eyes of 268 patients undergoing primary LASIK procedures by one surgeon utilizing the Moria LSK One microkeratome and VISX Star S-2 excimer laser., Methods: Corneal epithelial adhesion was assessed immediately preoperatively using a cellulose surgical sponge (adhesion test), and the incidence, extent, and location of epithelial defects occurring during the microkeratome incision of the corneal flap were recorded. Epithelial specimens from 7 corneas requiring debridement of dysadhesive epithelium were examined by transmission electron microscopy., Main Outcome Measures: The characteristics of the study population (age, gender, contact lens use, relevant ocular surface or systemic disease, refractive error, keratometry, pachymetry) and the microkeratome-related variables (head selection and vacuum level) were compared with the results of the preoperative epithelial adhesion test, the development of intraoperative epithelial effects (size and location), and the postoperative outcome., Results: Epithelial defects were sustained by 51 corneas (10.2%), and among these, 31 (6.2%) were microdefects and 20 (4.0%) were macrodefects. The adhesion test was positive (indicative of compromised adhesion of epithelium to stroma) in 20 (64.5%) corneas with microdefects, but false negatives (epithelial defect despite negative adhesion test) occurred in 11 cases (35.4%). The adhesion test was positive in 16 (80%) of corneas having macrodefects, with 4 (20%) false negatives. Thus, the overall positive predictive value of the adhesion test was 59%, and the percentage of positive prediction was 92% (Bayes' theorem). Among all other outcome measures assessed, only corneal flap thickness seemed a potential risk factor, as 40 (78.4%) epithelial defects were associated with the creation of a 180- micro m-thick flap, whereas 10 (19.6%) were associated with a 160- micro m-thick flap and only 1 (2%) occurred with a 130- micro m flap. These trends were not, however, statistically significant (P = 0.15, Fisher exact test). Transmission electron microscopy of all epithelial debridement specimens disclosed consistent abnormality of the basement membrane adhesion complex, as thickened and multilaminated basement membrane remained adherent to the intact epithelial sheet., Conclusions: : Corneal epithelial dysadhesion and defects occurring in the course of LASIK surgery may be associated with an intrinsic compromise of the basement membrane adhesion complex, as evidenced clinically by the adhesion test and demonstrated pathologically by duplicated basement membrane.

Background/purpose: Lamellar keratoplasty is an established therapy of corneal pathologies without endothelial involvement and the lack of endothelial rejection is one of the major advantages compared to penetrating keratoplasty. The major disadvantages of manually prepared lamellar corneal grafts are the limited mechanical and optical quality but the automated lamellar therapeutic keratoplasty system ALTK (MORIA) is intended to overcome these disadvantages. The purpose of this preliminary work is to investigate histologically and in clinical cases, if the ALTK system can achieve this aim., Patients and Methods: Corneas from two human donors were cut with a 300 microns trephine. After fixation, the stromal bed and the excised cup of one specimen were stained with PAS and examined by light microscopy and the other specimen was analyzed by scanning electron microscopy. In addition, follow-up data of two patients who received such a lamellar graft are reported for the first 9 and 7 months postoperation, respectively., Results: The lamellar cut of homogeneous depth revealed only minor stromal trauma. Both clinical cases demonstrated only minimal interface haze during follow-up. Despite a remarkably clear cornea, visual acuity improved only slowly because the precise lamellar cut tended to partially reproduce any preexisting irregular astigmatism., Conclusions: The ALTK system simplifies and standardizes the trephination of lamellar corneal grafts but a longer follow up is necessary with respect to visual development and preservation of a clear graft.

We demonstrate the applicability of optical coherence tomography to visualize the distance between the intraocular lens (IOL) and the lens capsule (lens vault) after implantation of the Staar Collamer posterior phakic IOL, also known as the implantable contact lens (ICL). Maintaining a substantial lens vault may be important to avoid cataract formation, but the lens vault was found to change over time; changes in accommodation and pupil size have also been noted. Optical coherence tomography allows precise assessment of the anatomic relationship between the ICL and the crystalline lens in a noncontact, noninvasive manner, permitting dynamic monitoring of changes in accommodation and pupil size.

Objectives: To determine the effect of amniotic membrane transplantation (AMT) on persistent corneal epithelial defects (PEDs) and to compare the efficacy between inlay and overlay techniques., Methods: Thirty patients (30 eyes) underwent AMT for PED. The use of AMT was restricted to patients in whom all previous measures, including bandage contact lens and tarsorrhaphy, had failed. The amniotic membrane was placed on the surface of the cornea in overlay (group A) or inlay (group B) fashion., Results: The PED healed after the first AMT in 21 eyes (70%) within an average of 25.5 days after surgery and recurred in 6 eyes (29%). Among the 22 eyes treated with an overlay AMT (group A), the PED healed after the first AMT in 14 eyes (64%) within an average of 24.5 days and recurred in 4 eyes (29%). Among the 8 eyes treated with an inlay AMT (group B), the PED healed within an average of 27.4 days after AMT, which did not statistically significantly differ from group A (P = .72). The PED healed after the first AMT in 7 eyes (88%) and recurred in 2 (29%) of 7 eyes., Conclusions: The AMT can be helpful in the treatment of PED in which all other conventional management has failed. However, the success rate in our study was not as high as that previously reported, and our results showed a high incidence of recurrences of epithelial defects. We did not find any difference between overlay and inlay techniques in terms of healing time and recurrence rate.

Purpose: To demonstrate the capability of a standard, commercially available optical coherence tomography device (originally designed to measure retinal thickness) to image the human cornea in vivo and to measure central corneal thickness (CCT) in normal and edematous corneas. The intrapatient precision and interpatient variability of this novel application was compared to standard ultrasonic pachymetry. Also, the correlation of both methods was investigated., Methods: CCT measurements using optical coherence tomography (OCT) and ultrasonic pachymetry (PACH) were obtained in 36 normal eyes and 16 eyes with corneal edema., Results: Direct in vivo imaging of the cornea and measurements of CCT by OCT could be performed in all eyes. In normal subjects, CCT(OCT) was 530+/-32 microm and CCT(PACH) was 581+/-34 microm. The two methods showed a highly significant correlation with a standardized regression coefficient of 0.988. The difference between both methods was constant over the range of CCT (mean difference, 49.4+/-5.9 microm). The mean intrapatient SD of CCT measurements was 4.90 microm and 4.96 microm for OCT and PACH, respectively. In patients with corneal edema, mean CCT(OCT) was 601+/-59 microm, and mean CCT(PACH) was 667+/-68 microm. The difference between the two techniques increased slightly with increasing corneal edema (mean difference, 66.9+/-10.9 microm)., Conclusion: Imaging of the human cornea can be performed by a standard retinal OCT device, and OCT measurement of CCT shows excellent correlation to values obtained by PACH, giving similar readings separated by a constant difference. In corneal edema, the difference between the two methods is additionally increased, but continues to demonstrate excellent consistency.

Purpose: To report the unusual manifestation of X-linked ichthyosis in two brothers., Methods: Leukocyte separation and sterylsulfatase assay are performed to show the deficiency of sterylsulfatase., Results: Two brothers presented in our clinic with cutaneous alterations consistent with X-linked ichthyosis. Ocular examination disclosed fine, flour-like, punctate, evenly, and diffusely distributed opacities of the posterior corneal stroma, close to Descemet membrane in both patients. In one patient, superficial, small, granular opacities were detected. They were gray in color and seemed to involve the epithelium and the subepithelial and anterior stromal layers. In both patients, the deficiency of sterylsulfatase could be shown and confirmed the diagnosis., Conclusions: Flour-like opacities in the posterior stroma have been shown to be a common manifestation of X-linked ichthyosis. Though the underlying biochemical defect in X-linked ichthyosis has been discovered, the question of how these opacities develop is still a subject of debate. Subepithelial stromal keratopathies or epithelial irregularities are uncommon and are rarely described in the literature. The superficial corneal changes seen in one of our patients are unusual and are not similar to those reported by other authors.

Background: Since a potential exists for untoward effects on the cornea from the high magnetic fields and radio-frequency energies, and the further manipulation required for phosphorus-31 magnetic resonance spectroscopy (31P-MRS), we determined the effects of this technology on tissues using paired human corneas (n = 4) meeting criteria acceptable for transplantation., Methods: Slit-lamp biomicroscopy, pachometry, specular microscopy, and redux fluorophotometry were performed on all corneas. One cornea of each pair was examined (< 30 min) by 31P-MRS. Following 31P-MRS, slit-lamp biomicroscopy, pachometry, and redox fluorophotometry were again performed., Results: Data tabulated included the 31P energy modulus (1.37 +/- 0.28), the ATP/Pi (2.92 +/- 0.59) and SP/Pi (0.76 +/- 0.04) ratios, and the intracorneal pH (7.24 +/- 0.09)., Conclusion: Since there were no significant differences in slit-lamp biomicroscopy, endothelial density and morphometry, cell counts, and pachometric and redox fluorophotometric measurements between corneas of each pair before and after 31P-MRS analysis, it was concluded that there was no detectable metabolic damage secondary to such analysis. This study suggests that MRS analysis of human eye-bank tissues does not damage the cornea metabolically and may provide a practical evaluation of the health of the cornea at the biochemical level.

Aims: To investigate the usefulness of ocular redox fluorometry for evaluating donor corneal endothelial viability., Methods: Corneas from 42 recipients of penetrating keratoplasty and four donor corneas were examined by ocular redox fluorometry. Autofluorescence from reduced pyridine nucleotides (PN) and oxidised flavoproteins (Fp) of the human corneal endothelium were measured non-invasively, and the PN/Fp ratio was used as a tissue metabolic indicator. Specular microscopy and electron microscopy were also performed., Results: Both the quality of specular microscopic image and the PN/Fp ratio were significantly correlated with the degree of corneal endothelial damage determined by histological examination. Corneas with poor specular microscopic image showed significantly decreased PN/Fp ratio compared with corneas with good or fair specular images (p = 0.041 and 0.027, respectively). The PN/Fp ratio increased in corneas with mildly damaged endothelium but decreased in corneas with severely damaged endothelium determined by histological examination. Evaluation of corneal endothelium by combination of specular microscopy and ocular redox fluorometry showed excellent association with that of histopathological examination (p < 0.0001)., Conclusion: Ocular redox fluorometry is useful for assessing donor corneal endothelial viability. Combination of ocular redox fluorometry and specular microscopy may increase the ability of donor cornea selection.

Because contact lens wear causes changes in tear film and corneal metabolism and can render the cornea susceptible to bacterial invasion, we examined the role of contact lens wear in Pseudomonas aeruginosa (P. aeruginosa) keratitis and its relation to the early defense mechanism, specifically whether the acute polymorphonuclear leukocyte (PMN) response is altered by contact lens wear. Thirty-three rabbit eyes were examined in an experimental model for P. aeruginosa keratitis. The development of bacterial invasion and PMN migration into the wound was studied during various time intervals in either the presence or absence of a soft hydrogel contact lens (SCL). Scanning electron microscopy revealed massive PMN accumulation in the P. aeruginosa-inoculated corneas without SCL and some, but distinctively fewer, PMNs in the bacteria-inoculated eyes with SCL. These observations demonstrate that P. aeruginosa inoculation evokes massive PMN reaction and suggests that SCL wear actually delays this early host inflammatory response. Thus, SCL wear seems to act as a barrier for the PMNs that presumably derive from the tear film.

The principles for management of acute ocular trauma are also applicable to the subsequent reconstruction of the anterior segment. As with the primary repair of ocular trauma, meticulous anatomical restoration during reconstructive surgery minimizes secondary complications and enhances the visual prognosis. Anterior segment reconstruction may then involve procedures such as stripping of corneal pannus, removal of lens and vitreous remnants, iris and angle reconstruction, intraocular lens implantation, and penetrating keratoplasty. A total of 39 consecutive cases of severe ocular trauma, which had undergone penetrating keratoplasty and anterior segment reconstruction, were evaluated for visual outcome, graft survival, and secondary complications. Post-operatively, 49% of eyes achieved > 20/100 as compared with 10% before surgery, and 72% improved by at least two Snellen lines. In all, 31 (80%) initial keratoplasties remained clear, as did all 4 subsequently regrafted corneas, 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 < 0.015). Peripheral anterior synechiae could be anatomically corrected at surgery in 80% of cases (24 of 30 eyes). Thus, despite major trauma and a high prevalence of glaucoma, both the visual and the anatomical improvements were highly satisfactory and without severe complications.

Injury to a vitamin A-deficient cornea leads to severe acute inflammation often culminating in ulceration. We report on possible regulatory mechanisms involved in the pathogenesis of corneal inflammation in vitamin A deficiency. Thymocyte comitogenic assay and interleukin (IL)-6 induction in corneal fibroblasts have shown that thermally injured and mechanically abraded vitamin A-deficient rat corneas produce much higher levels of an IL-1-like factor as compared with uninjured or injured, normal control corneas. This was confirmed by antibody capture enzyme immunoassay, which detected high levels of IL-1 alpha and IL-1 beta in injured vitamin A-deficient corneas. To our knowledge this is the first report describing the induction of IL-1 in the vitamin A-deficient cornea by thermal and mechanical injuries. When mechanically injured corneas were screened for chemotactic activity, they were found to contain significantly higher levels of a chemoattractant as compared with similarly injured, normal control corneas. Chemotactic activity [expressed as a percentage of a known chemotactic tripeptide, formyl-methionyl-leucyl-phenylalanine (fMLP), found in medium harvested from vitamin A-deficient corneas] averaged 58.8 +/- 8.9% (SEM) as compared with 12.6 +/- 5.4% in medium conditioned by normal corneas. Checkerboard analysis confirmed that the activity in vitamin A-deficient cornea conditioned medium was chemotactic and not chemokinetic. These results demonstrate a correlation between IL-1 levels and severity of inflammation in the injured vitamin A-deficient rat cornea.

This study assesses the impact of various forms of injury on matrix degrading enzymes in nutritionally compromised rat corneas. In vitamin A-deficient (nutritionally compromised) and normal control corneas, in vivo or ex vivo mild mechanical abrasion did not appreciably alter the activity of either the 65-kDa or the 92-kDa gelatinases. In contrast, after thermal injury, while no appreciable change was detected in activity associated with the 65-kDa gelatinase in either vitamin A-deficient or normal control corneas, 92-kDa gelatinolytic activity was consistently higher in corneas from both groups, although activity associated with nutritionally compromised corneas was much higher. In these corneas, thermal injury also induced the expression of two high molecular weight (approximately 130-kDa and 225-kDa) gelatinases and a 27-kDa caseinase. While gelatinases were totally inactivated by inhibitors of metalloproteinases such as 1,10-phenanthroline and Galardin MPI, the 27-kDa caseinase showed considerable susceptibility to a mixture of serine protease inhibitors (aprotinin, dichloro-isocoumarin and pA-PMSF [(4-amidino-phenyl)-methane-sulphonyl fluoride]. Furthermore, unactivated-lymphoreticular cells from either nutritionally compromised or normal control animals contained a 24- and 27-kDa caseinase, however most of the activity was due to the 24-kDa caseinase. In contrast, glycogen-activated lymphoreticular cells contained a preponderance of the 27-kDa caseinase. Activated-lymphoreticular cells also expressed 92-kDa, 130-kDa and 225-kDa gelatinases. The presence of low molecular weight caseinases in lymphoreticular cells implicates them as the source of these enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpose: Pseudophakic corneal edema is the principal indication for penetrating keratoplasty in the United States. Currently, three techniques of intraocular lens (IOL) fixation during penetrating keratoplasty for this condition are commonly used--flexible anterior chamber IOL (AC IOL) implantation, iris suture fixation of a posterior chamber IOL (PC IOL), and transscleral suture fixation of a PC IOL. This study represents the first prospective, randomized comparison of these three techniques., Methods: One hundred seventy-six consecutive patients with pseudophakic corneal edema who underwent penetrating keratoplasty with IOL exchange were randomized to one of the three implantation techniques. Standardized evaluations were performed at baseline and at 6, 12, and 18 months postoperatively. Life-table analysis provided cumulative risk estimates for specific complications., Results: Randomization produced comparable groups at baseline. The cumulative risk of macular edema was significantly less for the iris fixation cohort than for either the AC IOL or scleral fixation group. A complications index was constructed based on the major adverse outcomes of glaucoma escalation, cystoid macular edema, IOL dislocation, and graft failure. A significantly lower risk of complication was found for iris compared with scleral fixation of PC IOLs., Conclusion: The authors conclude that transscleral fixation of the PC IOL at the time of penetrating keratoplasty for pseudophakic corneal edema is associated with a greater risk of adverse outcome than iris fixation of a PC IOL.

Purpose: To understand the underlying mechanisms responsible for the easy removal and sloughing of corneal epithelium in vitamin A deficiency., Methods: An animal model of vitamin A deficiency, the vitamin A-deficient rat (A-rat), transmission electron microscopy, computer-assisted morphometric analysis and indirect immunofluorescence were used to study the adhesion of rat corneal epithelium to its basement membrane with emphasis on structure and molecular composition of the anchoring structures such as the hemidesmosome and bullous pemphigoid antigen., Results: Transmission electron microscopy resolved numerous microseparations of the basal epithelial cell membrane from the basement membrane with intervening segmental basement membrane duplications and electron dense deposits. Morphometric analysis disclosed a statistically significant reduction in the frequency and size of hemidesmosomes. Four weeks after supplementing the diet with retinyl acetate (700 micrograms/week), significant reversal of these same structural abnormalities could be detected. Immunofluorescence staining for bullous pemphigoid antigen, a component of the adhesion complex, showed intense staining of the basal epithelial cytoplasm but weak and discontinuous staining of the basement membrane. Weak staining for laminin was also evident in A- corneas. In contrast, normal corneas displayed no cytoplasmic staining for bullous pemphigoid antigen and intense staining of the basement membrane for bullous pemphigoid antigen and laminin., Conclusions: The authors propose that structural abnormalities of the epithelial basement membrane complex are responsible for the observed loose epithelial adhesion and sloughing, as well as other known abnormalities of healing in the vitamin A-deficient rat cornea.

Purpose: To examine the possibility that ocular surface epithelial cells might be grown in culture for use as grafts., Methods: The proliferative capacity of epithelial cells cultured from the conjunctiva, limbus, and central cornea of normal human eyes was compared. Single cells disaggregated from approximately 1 mm2 biopsy specimens were serially cocultured with lethally irradiated mouse 3T3 fibroblasts. To study the cells' ability to reform a stratified epithelium, confluent limbal cultures were released as an intact cell sheet with the enzyme Dispase and transplanted to a dermal connective tissue bed in nude mice. Attachment and differentiation properties of the reconstituted epithelium were examined immunohistochemically., Results: Central corneal epithelial cells could not be propagated; they senesced in first or second passage. In contrast, limbal epithelial cells exhibited a substantial (i.e., mean of 23 population doublings) and conjunctival cells a moderate (i.e., mean of 11 population doublings) proliferative capacity. Within 4 days of transplantation to the nude mouse dermis, cultured limbal epithelial cells formed an epithelium 5-6 cell layers thick. The epithelium adhered firmly to the graft bed, and deposition of the basement membrane and anchoring fibril protein collagens IV and VII and laminin was detectable immunohistochemically. The transplanted epithelium displayed limbuslike compartmental expression of keratins K3, K13, and K19, and of the enzyme enolase., Conclusions: These results support the concept that corneal epithelial stem cells are located in the limbus and indicate that cultured autologous limbal cells may function as grafts to permanently restore the corneal epithelium after severe ocular surface injury.

Purpose: To examine the effect of Pseudomonas aeruginosa on the expression of corneal matrix metalloproteases and the effect of its proteases on activation of corneal matrix metalloproteases in vitro., Methods: Rat corneas and human corneal fibroblasts were co-cultivated with two different strains (RPS & 599A) of P. aeruginosa and one strain of Staphylococcus aureus, and the conditioned media were analyzed for proteolytic activity by gelatin and casein zymography. Human corneal fibroblast-conditioned medium was incubated with that from either strain of P. aeruginosa and was analyzed in a similar manner., Results: Normal rat corneas in organ culture produce a 65 kDa gelatinase (inactive matrix metalloprotease-2), whereas thermally injured rat corneas additionally produce gelatinases with molecular masses of 92 kDa (inactive matrix metalloproteases-9) and > 200 kDa. Matrix metalloprotease-2 is also detected in human corneal fibroblast-conditioned medium. Although these matrix metalloproteases are no longer detectable when rat corneas or human corneal fibroblasts are co-cultured with two strains of P. aeruginosa for 48 hr, a 58 kDa gelatinase fragment appears in earlier stages of co-culture. In contrast, S. aureus does not affect matrix metalloprotease-2. The 58 kDa fragment is also evident by incubating human corneal fibroblast-conditioned medium with that from either strain of P. aeruginosa. Conditioned medium from the RPS strain, which produces both elastase and alkaline protease, is more effective in cleaving matrix metalloprotease-2 than that from the 599A strain, which expresses mainly alkaline protease., Conclusion: The secreted inactive corneal matrix metalloprotease-2 is activated through limited proteolysis by pseudomonal proteases.