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PURPOSE The purpose of this study was to report the indications, ocular and systemic comorbidities, and surgical outcomes of corneal transplantation in patients older than 90 years. METHODS A retrospective review was conducted to identify individuals 90 years and older who underwent corneal transplantation surgery at the Bascom Palmer Eye Institute between January 2013 and October 2020. Outcomes included best-corrected visual acuity and graft survival over time. Paired t tests were used to compare visual acuity preoperatively versus postoperatively. Graft survival was evaluated with Kaplan-Meier curves. RESULTS Fifty-eight eyes of 52 consecutive individuals were included. The mean age of individuals was 92 ± 2 years; 26.9% were male; and 48.1% self-identified as non-Hispanic White and 38.5% as Hispanic. Postoperative follow-up was 14.7 ± 12.1 months. Of the 58 eyes, 44.8% (26/58) underwent penetrating keratoplasty, 46.6% (27/58) Descemet stripping automated endothelial keratoplasty, and 6.9% (4/58) keratoprosthesis. All surgeries were performed under monitored local anesthesia, without major complications. Surgical indications included pseudophakic bullous keratopathy (36.2%), glaucoma-associated corneal decompensation (27.6%), Fuchs endothelial dystrophy (25.9%), and perforated corneal ulceration (19.0%). The best-corrected visual acuity improved by 0.32 (95% confidence interval 0.14-0.50; P < 0.01) as early as 1 month postoperatively, and vision gains were sustained for at least 12 months. Graft survival probability at 12 months was 88%. CONCLUSIONS Corneal transplantation is a safe and successful procedure in restoring the visual acuity for patients older than 90 years after careful preoperative evaluation. Further research is needed to evaluate the impact of corneal transplantation on quality of life in patients in the 10th decade of life.

PURPOSE: To investigate the association between corneal densitometry (CD) values from Scheimpflug tomography imaging, severity of guttae, and visual acuity (VA) in eyes with Fuchs Endothelial Corneal Dystrophy (FECD). DESIGN: Retrospective, cross-sectional study. SUBJECTS: Patients with FECD examined at the Bascom Palmer Eye Institute from January 2015 to September 2019. METHODS: We extracted CD values at central annuli of 0–2, 2–6, 6–10 and 10–12 mm from Scheimpflug tomography images. We investigated the association of corrected distance visual acuity (CDVA) with CD values, severity of guttae, central corneal thickness (CCT), cataract grade, refractive error, corneal edema grade, age, and gender using multivariate generalized estimating equation regression models. MAIN OUTCOME MEASURE(S): CDVA. RESULTS: 192 eyes from 110 patients were included in this study. Increase in central CD values at the 0–2 mm zone (P0.05) in the final multivariate regression model. CONCLUSIONS: Our study demonstrates that central CD values at 0–2 mm and severity of guttae are each associated with decreased CDVA in FECD. These findings carry implications for patients with FECD considering surgical intervention for phacoemulsification alone, Descemet stripping only (DSO) or endothelial cell transplantation, and provide a multifactorial perspective on vision loss in FECD.

Coronavirus disease 2019 (COVID-19), caused by novel enveloped single stranded RNA coronavirus (SARS-CoV-2), is responsible for an ongoing global pandemic. While other countries deployed widespread testing as an early mitigation strategy, the U.S. experienced delays in development and deployment of organism identification assays. As such, there is uncertainty surrounding disease burden and community spread, severely hampering containment efforts. COVID-19 illuminates the need for a tiered diagnostic approach to rapidly identify clinically significant infections and reduce disease spread. Without the ability to efficiently screen patients, hospitals are overwhelmed, potentially delaying treatment for other emergencies. A multi-tiered, diagnostic strategy incorporating a rapid host immune response assay as a screening test, molecular confirmatory testing and rapid IgM/IgG testing to assess benefit from quarantine/further testing and provide information on population exposure/herd immunity would efficiently evaluate potential COVID-19 patients. Triaging patients within minutes with a fingerstick rather than hours/days after an invasive swab is critical to pandemic response as reliance on the existing strategy is limited by assay accuracy, time to results, and testing capacity. Early screening and triage is achievable from the outset of a pandemic with point-of-care host immune response testing which will improve response time to clinical and public health actions.Key messagesDelayed testing deployment has led to uncertainty surrounding overall disease burden and community spread, severely hampering public health containment and healthcare system preparation efforts.A multi-tiered testing strategy incorporating rapid, host immune point-of-care tests can be used now and for future pandemic planning by effectively identifying patients at risk of disease thereby facilitating quarantine earlier in the progression of the outbreak during the weeks and months it can take for pathogen specific confirmatory tests to be developed, validated and manufactured in sufficient quantities.The ability to triage patients at the point of care and support the guidance of medical and therapeutic decisions, for viral isolation or confirmatory testing or for appropriate treatment of COVID-19 and/or bacterial infections, is a critical component to our national pandemic response and there is an urgent need to implement the proposed strategy to combat the current outbreak.

Ophthalmologists and patients have an inherent increased risk for transmission of SARS-CoV-2. The human ocular surface expresses receptors and enzymes facilitating transmission of SARS-CoV-2. Personal protective equipment alone provides incomplete protection. Adjunctive topical ocular, nasal, and oral antisepsis with povidone iodine bolsters personal protective equipment in prevention of provider-patient transmission of SARS-CoV-2 in ophthalmology.

Background/aimsAchromobacter xylosoxidans and Stenotrophomonas maltophilia are emerging corneal pathogens, which are closely related to Pseudomonas aeruginosa, and have intrinsic resistance to many commonly available antimicrobials. The purpose of this study is to compare the in vitro efficacy of 12 antimicrobial agents against A. xylosoxidans, S. maltophilia and P. aeruginosa isolates recovered from clinical cases of keratitis.MethodsRecovered corneal isolates (n=58) were identified and extracted from the Microbiology Data Bank of the Bascom Palmer Eye Institute. Comparative in vitro minimum inhibitory concentration (MIC) susceptibility profiles for fluoroquinolones, aminoglycosides, beta-lactams and miscellaneous antibiotics were recorded using the E-test methodology. Pharmacodynamic indices (Cmax/MIC) were calculated.ResultsA. xylosoxidans and S. maltophilia isolates were resistant to fluoroquinolones, aminoglycosides and ceftazidime (susceptibility rate ranging from 0% to 30%) while P. aeruginosa isolates showed a susceptibility rate of 95%–100% to these antimicrobials (PS. maltophilia isolates and Cmax/MIC=10.19. Ninety to 100% susceptibility rates were found for minocycline and trimethoprim/sulfamethoxazole for both A. xylosoxidans and S. maltophilia. One hundred per cent of the A. xylosoxidans isolates were susceptible to piperacillin/tazobactam and ticarcillin/clavulanic acid.ConclusionsThere is a significant difference in susceptibility patterns between A. xylosoxidans, S. maltophilia and P. aeruginosa. Fluoroquinolones and aminoglycosides may not be effective against A. xylosoxidans and S. maltophilia. Antibiotics that are not commercially available as eye drops, such as beta-lactams for A. xylosoxidans, and trimethoprim/sulfamethoxazole and minocycline for both A. xylosoxidans and S. maltophilia should be considered.

To compare corneal graft survival rates after penetrating keratoplasty (PK) and Descemet’s stripping endothelial keratoplasty (DSEK) in patients with a glaucoma drainage device (GDD) or medically managed glaucoma. A retrospective chart review was conducted on consecutive patients who underwent primary PK or primary DSEK. Inclusion criteria consisted of eyes with a diagnosis of glaucoma prior to corneal transplantation and a minimum of 6 months of follow-up. Graft failure was defined as an edematous cornea with failure to maintain deturgescence lasting beyond a period of 1 month of intense steroid therapy or vascularization and scarring resulting in irreversible loss of central graft clarity. Corneal graft survival was calculated using Kaplan–Meier survival analysis. Patients were divided into four groups: GDD-PK, GDD-DSEK, medical-PK and medical-DSEK. Fifty-six eyes of 56 patients were identified as meeting inclusion criteria. Among eyes with a GDD, there was no difference in the proportion of failures between PK grafts (48%) and DSEK grafts (50%) (p = 0.90). Failure occurred earlier in DSEK recipients compared to PK recipients, 5.82 ± 6.77 months versus 14.40 ± 7.70 months, respectively (p = 0.04). A Kaplan–Meier analysis did not identify a difference between the four groups with respect to graft failure (p = 0.52). There is no significant difference in graft survival rates between medically and surgically treated glaucoma patients for either PK or DSEK grafts. In patients with GDD, graft failure occurs earlier in DSEK compared to PK.

Purpose of review The present review provides an overview on the potential of different systemic and topical treatments in chronic forms of ocular allergy and dry eye disorder (DED). The impact on anterior surface of ocular inflammatory disorder encompasses an array of conditions, which are frequently underreported. This can contribute to underdiagnoses and ineffective management from healthcare providers such as an allergist and/or ophthalmologist who routinely provide care for these common disorders. Owing to the current limited therapeutic options, healthcare providers are routinely seeking alternative treatments that could facilitate effective management of the conditions. Recent findings Recent advances in immunopathophysiology of ocular surface disorders has provided new potential targets and therapeutic strategies for the treatment of DED and ocular allergy that may include various immunobiological modulators. These modulators have focused on regulating the Th1 and Th2 immune-mediated inflammatory pathways that inhibit various cytokines (e.g. IL-1, IL-4, IL-5, IL-9, IL-13) antibodies (e.g. IgE), and other surface markers of various cell lines (e.g. activated T-lymphocytes, lymphocyte function-associated antigen-1). Summary Recent findings about the pathophysiology of DED and ocular allergy have led to the greater understanding of the molecular and cellular mechanisms of ocular surface diseases leading to the potential novel targets for immunomodulation of anterior surface ocular disorders. New topical glucocorticoids, leukotriene receptor antagonists, IL-1 antagonists, IL-5, IL-4/IL-13 antagonists, integrin antagonists, and quinolone derivatives appear to be encouraging.

Background A major obstacle that academic institutions face is the steep learning curve for cornea fellows initially learning to perform Descemet Stripping Endothelial Keratoplasty (DSEK). The purpose of this study is to evaluate the outcomes of complex DSEK performed by cornea fellow supervised by an attending surgeon at an academic institution. Methods Patients who underwent a complex DSEK procedure performed by a cornea fellow during the years 2009-2013 were included. All the surgeries were supervised by the same cornea attending. All patients had a minimum follow-up of 6 months. Charts were reviewed for demographic data, intraoperative and postoperative complications and clinical outcomes. Corneal graft survival was calculated using the Kaplan-Meier analysis. Results Fifty-seven eyes of 55 patients (mean age 77.5 ± 8.5 years) were included in the study with a mean follow-up time of 16.4 ± 15.6 months. Previous graft failure, presence of a tube and history of trabeculectomy were the leading diagnoses to define the surgery as complex. No intraoperative complications occurred. In 21.1% of cases a corneal graft detachment was documented in the first postoperative day. Mean visual acuity improved from 1.06 LogMAR (20/230) preoperatively to 0.39 LogMAR (20/50, p

Recovered corneal isolates (n=58) were identified and extracted from the Microbiology Data Bank of the Bascom Palmer Eye Institute. Comparative in vitro minimum inhibitory concentration (MIC) susceptibility profiles for fluoroquinolones, aminoglycosides, beta-lactams and miscellaneous antibiotics were recorded using the E-test methodology. Pharmacodynamic indices (Cmax/MIC) were calculated.There is a significant difference in susceptibility patterns between

Purpose To assess aqueous humor concentration of prostaglandin E2 (PGE2) after capsulotomy creation using a femtosecond laser (FLAC) in patients pretreated with short-term topical ketorolac versus patients without pretreatment. Methods This prospective study comprised consecutive patients scheduled to undergo cataract surgery using a femtosecond laser platform to perform only capsulotomies. An identical protocol for preoperative mydriasis was used for all the eyes included in the study, while aqueous humor was extracted from the anterior chamber of all patients immediately after the initial side port incision. ELISA was performed to quantify aqueous humor PGE2. The patients were divided into 2 groups; in group 1, the patients received short-term topical ketorolac preoperatively, while the patients in group 2 did not receive NSAID pretreatment. Results Twenty eyes of 20 patients were included in the study (10 eyes in each group). Mean concentration of aqueous humor PGE2 after FLAC was 392.16 ± 162.00 pg/ml and 622.63 ± 331.84 pg/ml for groups 1 and 2, respectively. A statistically significant difference in aqueous humor PGE2 concentration between the two groups (p < 0.05) was demonstrated, with the eyes that received ketorolac pretreatment demonstrating a lower concentration of PGE2. Conclusion Short-term topical use of ketorolac prior to FLAC seems to prevent excessive release of PGE2 in the anterior chamber of the eyes that received NSAID pretreatment when compared to the eyes that did not receive NSAIDs preoperatively.

To compare the nucleus removal time (NRT) and cumulative dissipated energy (CDE) outcomes of traditional phacoemulsification and femtosecond laser-assisted cataract surgery (FLACS) performed by cornea attendings and fellows.Prospective nonrandomized comparative study.A total of 410 eyes of 410 patients.Nucleus removal time and CDE were recorded from patients who underwent cataract surgery using either FLACS (Catalys, LenSx, or Victus) or traditional phacoemulsification technique performed by 3 cornea attendings and 4 cornea fellows. One-way analysis of variance with Bonferroni post hoc tests and unpaired t tests were used to determine the differences between groups.There was no statistically significant difference in cataract grade between groups. NRT was significantly lower only when using the Catalys system compared with the LenSx and Victus platforms and the traditional surgery, in both the attending group (p = 0.006, p = 0.002, p0.000, respectively) and the fellow group (p = 0.049, p = 0.038, p = 0.011, respectively). With respect to CDE, there was no significant difference when using the laser systems compared with the traditional surgery in both attending and fellow groups (p0.05). NRT and CDE were significantly higher in the fellow group (NRT = 269.10 ± 117.67, CDE = 7.30 ± 4.83) compared with the attending group (NRT = 218.87 ± 109.67, CDE = 5.76 ± 3.66) in traditional cases; however, in FLACS cases, there was no significant difference in NRT and CDE between the fellow group and the attending group.Inexperienced surgeons seem to require more time and use more ultrasound energy during traditional phacoemulsification when compared with experienced surgeons. The use of FLACS seems to significantly improve the NRT of experienced and inexperienced surgeons.

The focus of this review is to provide a logical paradigm for the diagnosis and treatment of ocular allergies, with a focus on seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC).Several classes of topical medications are currently available for the management of ocular allergies, including: lubricating agents, vasoconstrictors, antihistamines, mast cell stabilizers, and topical corticosteroids.SAC and PAC make up the vast majority of ocular allergy cases. A proactive approach to these diseases, anticipating the regional spring and fall allergen spikes, is needed for optimally managing these disorders. A multifaceted treatment regimen comprising patient education, lifestyle modification, and topical medications (such as antihistamines and/or mast cell stabilizers and corticosteroids) may be required in order to manage ocular allergies effectively. The appropriate treatment paradigm is based on the severity of the patients' signs and symptoms. For moderate-to-severe cases, especially chronic vernal keratoconjunctivitis, atopic keratoconjunctivitis, and giant papillary conjunctivitis, comanagement with an ophthalmologist is recommended.

Purpose To describe a case of a second application of femtosecond laser-assisted capsulotomy to achieve a complete treatment pattern after an initial incomplete capsulotomy creation due to loss of suction. Methods A 66-year-old woman presented with visually significant cataract in both eyes. She was scheduled to undergo femtosecond laser-assisted cataract surgery (FLACS) using the Victus platform. During FLACS capsulotomy of the right eye (capsulotomy diameter set at 5.0 mm), loss of suction occurred followed by laser treatment interruption, resulting in an incomplete, discontinuous capsulotomy treatment pattern. A second FLACS pretreatment was performed immediately after the first incomplete treatment, aiming for a capsulotomy diameter 0.1 mm larger than the previous (5.1 mm in diameter) and with placement of the capsulotomy treatment outside the prior incomplete capsulotomy. Results A complete continuous treatment pattern was achieved for the capsulotomy after second application of FLACS pretreatment. No intraoperative complications were noticed. Conclusion A second application of femtosecond laser-assisted capsulotomy to achieve a complete treatment pattern after initial incomplete capsulotomy creation due to loss of suction is feasible during the same surgical setting.

To compare in vitro susceptibility of amphotericin B (AMB) and amphotericin B methyl ester (AME) (a more soluble and less toxic formulation of AMB) against Candida albicans isolates recovered from human cases of endophthalmitis.The in vitro susceptibility of AMB and AME was determined for C. albicans isolates recovered from endophthalmitis (N=10) and for C. albicans ATCC reference strain 90028 using the Clinical and Laboratory Standards Institute M27-A2 (NCCLS/CLSI) broth dilution method. All isolates were obtained from samples of vitreous humor of patients with suspected endophthalmitis within the last 5 years at the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine (Miami, FL).The minimal inhibitory concentrations (MICs) of AME were equal to or lower than values for AMB in 7 of the 10 isolates; range: AME (0.125-1 μg/mL) versus (0.5-1 μg/mL) for AMB. The MIC(90) value of both drugs was equal (1 μg/mL). Compared with AMB, the minimal fungicidal concentrations (MFCs) of AME were equal to or lower in 8 of 10 isolates; range: AME (0.125-2 μg/mL) versus AMB (0.25-4 μg/mL). MFC(90) values of AME (1 μg/mL) was slightly superior to AMB (2 μg/mL). The MIC of the quality control strain (ATCC(®) 90028) was within an acceptable range.AME was equivalent to AMB in vitro against C. albicans. This formula may offer a slightly more efficient and less toxic formulation for the treatment of Candida endophthalmitis.

Acute bacterial conjunctivitis, the most common cause of conjunctivitis, is responsible for approximately 1% of all primary-care consultations. Of the topical ophthalmic antibiotics used to treat acute bacterial conjunctivitis, fluoroquinolones are especially useful because they possess a broad antibacterial spectrum, are bactericidal in action, are generally well tolerated, and have been less prone to development of bacterial resistance. Besifloxacin, the latest advanced fluoroquinolone approved for treating bacterial conjunctivitis, is the first fluoroquinolone developed specifically for topical ophthalmic use. It has a C-8 chlorine substituent and is known as a chloro-fluoroquinolone. Besifloxacin possesses relatively balanced dual-targeting activity against bacterial topoisomerase IV and DNA gyrase (topoisomerse II), two essential enzymes involved in bacterial DNA replication, leading to increased potency and decreased likelihood of bacterial resistance developing to besifloxacin. Microbiological data suggest a relatively high potency and rapid bactericidal activity for besifloxacin against common ocular pathogens, including bacteria resistant to other fluoroquinolones, especially resistant staphylococcal species. Randomized, double-masked, controlled clinical studies demonstrated the clinical efficacy of besifloxacin ophthalmic suspension 0.6% administered three-times daily for 5 days to be superior to the vehicle alone and similar to moxifloxacin ophthalmic solution 0.5% for bacterial conjunctivitis. In addition, besifloxacin ophthalmic suspension 0.6% administered two-times daily for 3 days was clinically more effective than the vehicle alone for bacterial conjunctivitis. Besifloxacin has also been shown in preclinical animal studies to be potentially effective for the "off-label" treatment of infections following ocular surgery, prophylaxis of endophthalmitis, and the treatment of bacterial keratitis. Taken together, clinical and preclinical animal studies indicate that besifloxacin is an important new option for the treatment of ocular infections.

Seasonal allergic conjunctivitis (SAC) is an inflammatory response of the conjunctiva triggered by exposure to seasonal allergens. Treatment options for SAC include artificial tears, antihistamines, decongestants, mast cell stabilizers, nonsteroidal anti-inflammatory drugs, dual antihistamine/mast cell stabilizers, immunotherapy and corticosteroids. Topical, intranasal and systemic formulations of corticosteroids have traditionally provided the most effective relief of the inflammation and signs and symptoms associated with severe, acute exacerbations of SAC. However, steroid-induced ocular and systemic side-effects have limited the prescribing of these agents. This limitation of traditional corticosteroids led to the development of modified corticosteroids that retain the anti-inflammatory mechanism of action of traditional corticosteroids with a much-improved safety profile because of their rapid breakdown to inactive metabolites after exerting their activity. The development of one such novel corticosteroid, loteprednol etabonate (LE), led to the insertion of an ester (instead of a ketone) group at the carbon-20 (C-20) position of the basic corticosteroid structure. Clinical trials assessing this C-20 ester corticosteroid have demonstrated similar efficacy to C-20 ketone corticosteroids in the prevention or treatment of the signs and symptoms of SAC but with a greatly improved safety profile, as the C-20 ester corticosteroid is less likely to elevate intraocular pressure. In addition, the ketone at the C-20 position has been implicated in the formation of cataract, while nonketolic corticosteroids do not form Schiff base intermediates with lens proteins, which is a common first step in cataractogenesis. The clinical relevance of the C-20 ester corticosteroid class, as modelled by LE, is that they provide both effective and safe treatment of the inflammation associated with SAC and relief of its signs and symptoms. Loteprednol etabonate offers a well-tolerated treatment option for patients with debilitating acute exacerbations as well as chronic forms of the disease.

Background: The trend in current cataract surgery towards clear corneal incision and sutureless procedures makes us realize the importance of wound construction. For optimal surgical outcomes, we need good surgical instruments. In this study, we employed a resistance recording system to analyze the characteristics of seven commercially available disposable cataract knives and to find clues for the future development of ‘good’ cataract knives. Methods: The cutting resistance was recorded during perpendicular penetrations of porcine scleral tissues by cataract knives. This data was processed and analysed mathematically with MATLAB software (The MathWorks, Inc, Natick, MA, USA) to see the resistance wave shapes and their derivatives to show the products' differing characteristics. Results: The wave shapes demonstrated product-dependent characteristics. The average maximum penetration resistance varied from 86.4 to 233 mN. The first order time derivatives also showed distinctive wave shapes. Conclusion: We used an experimental model to analyze one aspect of a knife's character. This model can help give clues for future developments, although this is the initial step.

Effective ocular tissue concentrations and prolonged residence times of antibacterial agents are important in treating both acute and chronic diseases. Conjunctival biopsy allows the determination of specific tissue concentration data for topical ophthalmic agents. Drug concentration analysis at various time points following instillation allows interpretation of the residence time and a rationale for dosing frequency.This study compared the pharmacokinetic parameters of 2 currently available topical ocular antibiotics-azithromycin ophthalmic solution 1% and moxifloxacin ophthalmic solution 0.5%-in the conjunctiva of healthy volunteers after a single topical administration.This single-dose, randomized, open-label, active-controlled clinical trial was conducted at ORA Clinical Research and Development, North Andover, Massachusetts. Subjects were randomly assigned to receive a single dose of azithromycin or moxifloxacin and to undergo biopsy sampling at 30 minutes or 2, 12, or 24 hours after administration. Concentrations of azithromycin and moxifloxacin were determined using liquid chromatography tandem mass spectrometry. Adverse events (AEs) were assessed at all visits using visual acuity measurements, slit-lamp biomicroscopy, and direct questioning.Forty-eight subjects (mean age, 40.0 years; 48% female; 96% white, 2% black, and 2% Asian) underwent conjunctival biopsy. Mean (SD) concentrations of azithromycin in conjunctival tissue (lower limit of quantitation [LLOQ], 1 microg/g for 1-mg biopsy specimen) were 131 (89), 59 (19), 48 (24), and 32 (20) microg/g at 30 minutes and 2, 12, and 24 hours, respectively (median values, 117, 69, 46, and 30 microg/g). Mean concentrations concentrations of moxifloxacin in conjunctival tissue (LLOQ, 0.05 microg/g for 1-mg biopsy sample) were 1.92 (2.03), 3.77 (8.98), 0.02 (0.04), and 0.01 (0.02) microg/g at 30 minutes and 2, 12, and 24 hours, respectively (median values, 1.12, 0.12,0.05, and0.05 microg/g). Thirteen subjects (6 in the azithromycin group and 7 in the moxifloxacin group) experienced 20 AEs, 11 of which were considered possibly related to study treatment, and 15 of which were ocular (most commonly conjunctival hemorrhage).In this single-dose study of 2 currently available topical ocular antibiotics in healthy volunteers, therapeutic concentrations were achieved with both agents. Both treatments were well tolerated in the population studied. Clinical Trials Identification Number: NCT00564447.

Purpose To compile a survey of complications during and after Descemet's stripping with automated endothelial keratoplasty (DSAEK) in 118 eyes conducted by cornea subspecialists at a single academic center. Design Retrospective case series. Participants One hundred eighteen eyes undergoing DSAEK in 99 patients. Methods Outcomes of DSAEK performed in 118 eyes by 10 surgeons were reviewed retrospectively. Sixty-four eyes had pseudophakic bullous keratopathy. Forty-one had Fuchs' endothelial dystrophy and cataract. Three had aphakic bullous keratopathy. In 10 eyes, previous DSAEK performed at the same institution failed. Complications of DSAEK were noted from the intraoperative and postoperative periods. Detached DSAEK grafts were repositioned, rebubbled, or both immediately after diagnosis of this complication. Main Outcome Measures Intraoperative and postoperative complications of DSAEK. Results Graft detachment was the most common type of complication encountered. In 27 (23%) of 118 eyes, graft detachments were observed. Twenty-five eyes with detached grafts successfully were repositioned or rebubbled after surgery, or both. In 1 eye, a previously detached graft reattached spontaneously. In 1 aphakic eye, the graft detached into the vitreous cavity. In 17 eyes, successful reattachment of the cornea occurred (68%). Twenty-one of the 118 eyes were considered to have failed DSAEK, meaning that persistent edema was present after DSAEK. Seven (6%) demonstrated graft rejection. In 5 eyes (4%), retinal detachment (RD) developed. In 6 (5%), cystoid macular edema developed. In 1 aphakic patient, an air bubble could not be maintained during surgery, and sulfur hexafluoride was injected into the anterior chamber. In 1 eye (1%), epithelial ingrowth developed. One eye (1%) demonstrated blood in the graft interface. In 1 eye (1%), a limited intraoperative suprachoroidal hemorrhage occurred. Two eyes (2%) had pupillary block after surgery that resolved with removal of the air bubble. Conclusions Descemet's stripping with automated endothelial keratoplasty has become a popular and effective treatment for corneal endothelial dysfunction, but complications resulting from DSAEK do occur. Graft detachment is the most common complication, but postoperative repositioning or rebubbling, or both, allow for graft reattachment in most cases. Other complications found in this series were graft failure, graft rejection, cystoid macular edema, RD, suprachoroidal hemorrhage, and pupillary block. Retained Descemet's membrane and epithelial ingrowth, are potential causes of dislocation. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

To compare the effect of storing Descemet-stripping automated endothelial keratoplasty (DSAEK) tissue with anterior lamellar corneal tissue (ALCT)-on versus -off.An in vitro model was used with corneoscleral rims and DSAEK quality paired corneas. After microkeratome-assisted excision of ALCT, 4 pairs of corneas (8 eyes) were stored with the ALCT left on the stroma (on) and the others with ALCT off the stroma (off) for 24 hours in Optisol GS solution. A vital dye assay was used to identify devitalized and necrotic endothelial cells with alizarin red S and trypan blue.Corneal endothelial cell damage was observed in the ALCT-off specimens, whereas almost no staining was observed in the ALCT-on samples. In addition, the ALCT-off donor corneas were clinically edematous and opaque, whereas the ALCT-on corneas were clear. Moreover, Descemet membranes of ALCT-off samples were found to be loose and easily detached from the stroma, with many Descemet striae observed in the specimens.This study shows that endothelial damage occurs in ALCT-off corneas. We hypothesize that the absence of the Bowman layer may contribute to the damage, because it has been shown that the Bowman layer provides a barrier function. These data suggest that it is important to keep the ALCT/Bowman layer on the stromal side of the DSAEK graft as long as possible to avoid stromal swelling and endothelial damage.

Femtosecond laser technology (IntraLase, Irvine, CA, USA) has been introduced in corneal surgery, opening a new frontier and providing a new surgical modality. The purpose of this study is to present a series of patients with keratitis after Femtosecond-assisted diagnostic corneal biopsies (FAB).Four patients with progressive keratitis--despite intensive broad-spectrum topical antimicrobial therapy, or progressive stromal infiltration inaccessible to corneal scrapings--underwent femtosecond-assisted diagnostic corneal biopsy. A corneal specimen was obtained using the Femtosecond laser (IntraLase), including both clinically infected and adjacent non-infected clear corneal tissue. A combination of lamellar and keratoplasty treatment parameters were used.Corneal specimens of 3 mm diameter and 120 to 200 microm thickness were obtained in all patients. No intra- or early post-operative complications related to the procedure were found. In all patients, adequate specimens were submitted for cultures, smears, and permanent section staining.In this small case series of patients with undiagnosed keratitis, femtosecond-assisted diagnostic corneal biopsy (FAB) obtained adequate specimens without intra- or early post-operative complications, related to the procedure.

Olopatadine hydrochloride 0.2% (Pataday, Alcon, Fort Worth, USA) is a topical ocular anti-allergic agent that has shown high rates of efficacy in treating ocular itching, the primary symptom of allergic conjunctivitis, and allows for once-daily dosing. Since some patients suffer from signs or symptoms of dry eye in addition to ocular allergy, this study was designed to evaluate the safety of olopatadine 0.2% in a population of patients with both allergic conjunctivitis and dry eye.This was a single-center, 3-visit, double-masked, randomized study. Fifty-two patients diagnosed with ocular allergy and mild-to-moderate dry eye were evaluated. After a run-in period, patients were randomized to receive either olopatadine hydrochloride 0.2% or a tear saline, and self-dosed once-daily for 1 week. Outcome measures included tear film break-up time, corneal and conjunctival staining, tear volume and flow as measured by fluorophotometry, Schirmer's test, injection, and symptom evaluations.No significant differences between the treatment groups were observed (p0.05). No serious adverse events occurred during the trial. Variability in the presentation of dry eye can hinder the observation of treatment effects. Although the study design facilitated the comparison of olopatadine 0.2% against an agent that was certain to not exacerbate dry eye, future comparison of olopatadine 0.2% against other agents in its drug class would provide useful information about relative drug tolerabilities.As there were no significant changes in the signs and symptoms of dry eye, olopatadine hydrochloride 0.2% is safe to use in ocular allergy patients with mild-to-moderate dry eye.

This analysis provides guidelines for the proper use of topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs), discusses their effect on inflammation, and their role in the prevention of cystoid macular edema (CME). A novel treatment strategy is presented for recommended topical ophthalmic NSAID dosing in patient populations based on risk factors for CME. The article reviews current topical ophthalmic NSAIDs, as well as a newest generation of pro‐drug NSAIDs. In addition, combination therapy of NSAIDs and corticosteroids are discussed, along with a general review of therapeutic guidelines for dosing regimens, and benefits and risks of therapy. The goal of this analysis is to provide a suggested therapeutic regimen with topical NSAIDs to assist in achieving optimal clinical and functional outcomes.

PURPOSE The purpose of this study was to assess interocular corneal symmetry in average simulated keratometry, corneal thickness, and posterior corneal elevation. METHODS This retrospective analysis included data from scanning slit topography (Orbscan II; Bausch and Lomb, Rochester, NY) on 242 eyes from 121 consecutive patients undergoing standard evaluation for consideration of elective laser vision correction. The symmetry between the right and left eye in average simulated keratometry, minimum central corneal thickness, and posterior corneal elevation was assessed by comparative data analysis. RESULTS Simulated keratometry ranged from 39.9 to 48.6 D. The interocular difference in average simulated keratometry was 0.47 D (standard deviation [SD] 0.43). The interocular Pearson correlation coefficient for average simulated keratometry was 0.90 (p < 0.001). The range of minimum corneal thickness was 432 to 628 microm. The interocular Pearson correlation coefficient for minimum central corneal thickness was 0.95 (p < 0.001). Right and left eye minimum corneal thickness differed by an average 8 microm (SD 7). The range of posterior elevation was -4 to 54 microm. The average difference in posterior corneal elevation between the right and left eye was 6 microm (SD 5). The interocular Pearson correlation coefficient for posterior corneal elevation was 0.72 (p < 0.001). The average posterior elevation was 19 microm (SD 11). CONCLUSIONS Although a wide range of values exists in simulated keratometry, minimum corneal thickness, and posterior corneal elevation, interocular symmetry in all these parameters was very high in this group of consecutive patients. Asymmetry of these interocular parameters may warrant repeat clinical testing for accuracy and may predict corneal abnormalities. Normative data on posterior cornea elevation is presented. This study points out potentially clinically important high interocular corneal symmetry data in simulated keratometry, corneal thickness, and posterior corneal elevation.

Purpose To evaluate improvement in best spectacle-corrected visual acuity (BSCVA) after laser in situ keratomileusis (LASIK) in adult patients with amblyopia. Setting Refractive Eye Surgery Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Methods The charts of consecutive patients with a diagnosis of amblyopia at the time of refractive evaluation who had LASIK were reviewed retrospectively. The preoperative and postoperative uncorrected visual acuity (UCVA) and BSCVA were analyzed. Results Twenty-one eyes of 19 patients were identified as having amblyopia and LASIK surgery. Eight patients (42.1%) were diagnosed with amblyopia only, 6 patients (31.6%) had anisometropic amblyopia, 4 patients (21.1%) had strabismic amblyopia, and 1 patient (5.2%) had anisometropic and strabismic amblyopia. Eleven eyes (52.4%) had myopic astigmatism, 7 eyes (33.3%) were hyperopic, and 3 eyes (14.3%) had mixed astigmatism. Seven eyes (33.3 %) experienced more than a 1-line improvement in postoperative UCVA compared with the preoperative BSCVA. Nine eyes (42.8%) experienced more than a 1-line improvement in postoperative BSCVA compared with the preoperative BSCVA. The BSCVA was unchanged in 11 eyes (52.4%) and was worse by 2 lines in 1 eye (4.8%). Conclusion After LASIK, the postoperative BSCVA was better than preoperatively in 42.8% of eyes with a history of amblyopia and the postoperative UCVA was better than the preoperative BSCVA in 33.3%.

Intravitreous (i.v.t.) injection is increasingly being incorporated into the management of ocular diseases. While only fomivirsen sodium (Vitravene) is currently approved by the Food and Drug Administration as an i.v.t. injection, the number of approved i.v.t. injections indications is anticipated to grow on the basis of promising results from ongoing clinical studies. Despite the potential benefits that may be derived from intraocular injections of different agents, no guidelines have been published previously for i.v.t. injection. The purpose of this document is to identify specific strategies for the delivery of i.v.t. injection that may reduce risks and improve outcomes. Consensus was sought among a panel of investigators, surgeons experienced with this technique, and industry representatives. Objective evidence was sought for all guidelines, but consensus was accepted where evidence remains incomplete. In the absence of either evidence or consensus, the current manuscript identifies outstanding issues in need of further investigation. It is anticipated that more complete guidelines will evolve over time, potentially altering some of the guidelines included here, based on new applications of i.v.t. injection, additional clinical experience, and results of clinical trials.

To compare the incidence of intraoperative corneal abrasions using the Hansatome (Bausch & Lomb Surgical) and Amadeus (Advanced Medical Optics) microkeratomes and to determine whether there is a correlation between patient age and the occurrence of intraoperative corneal abrasions. Outpatient ambulatory laser vision correction center. The charts of 133 patients (263 eyes) having laser in situ keratomileusis (LASIK) were reviewed retrospectively. The patients were randomized to LASIK performed by 2 surgeons using the same technique with alternative microkeratome selection. The incidence of intraoperative corneal abrasions was significantly higher with the Hansatome microkeratome than with the Amadeus microkeratome (P =.014). There was a significant correlation between increasing patient age and the incidence of corneal abrasions with both microkeratomes (P

Purpose To assess the effects of nonsteroidal antiinflammatory drug (NSAID) eyedrops on the expression of matrix metalloproteinases in corneal tissue. Setting Ocular Microbiology and Immunology Laboratory, Refractive Surgery Research Laboratory, The Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA. Methods Seventy rats were divided into 2 groups: intact and debrided epithelium. Uniform central corneal epithelial defects were created in the right eye of the debrided corneal group. Each group was divided into 4 subgroups, each receiving 1 of the following eyedrops or artificial tears: The 3 NSAIDs were diclofenac sodium 0.1% (Falcon® or Voltaren®) and preservative-free ketorolac 0.5% (Acular® PF). The artificial tears were carboxymethylcellulose sodium 0.5% (Refresh Plus® PF). The eyedrops were administered 4 times a day for 1 week. The rats were killed on days 2 and 7. The corneas were excised and processed for immunohistochemical staining, Western blot assay, and zymography studies to determine the localization of the production of the following matrix metalloproteinases (MMPs): MMP-1, MMP-2, MMP-8, and MMP-9. Results Matrix metalloproteinase-1, MMP-8, and MMP-2 were detected in rat corneas at 48 hours in the debrided and intact epithelium groups treated with NSAID eyedrops. The MMP-1 and MMP-8 expression levels were higher in intact corneas in the diclofenac sodium groups than in the ketorolac and artificial tears groups. The expression was localized mostly in the epithelial cells and occasionally in keratocytes. Conclusion This study provides preliminary evidence that topical application of some NSAIDs can induce the early expression of MMP-1, MMP-2, and MMP-8 in the cornea, suggesting that MMPs play a role in the corneal cytotoxicity of certain NSAIDs.

Purpose To compare corneal graft survival rate after primary Descemet9s stripping endothelial keratoplasty (DSEK) and primary penetrating keratoplasty (PK) in patients with prior trabeculectomy or medically managed glaucoma. Methods A retrospective chart review was conducted on consecutive patients who underwent DSEK or PK. Inclusion criteria consisted of eyes with a diagnosis of glaucoma prior to corneal transplantation and ≥6 months of follow-up. Graft failure was defined as an oedematous cornea with failure to maintain deturgescence lasting beyond a period of 1 month of intense steroid therapy or vascularisation and scarring resulting in irreversible loss of central graft clarity. Corneal graft survival was calculated using Kaplan–Meier survival analysis. Patients were divided into four groups: trabeculectomy-DSEK, trabeculectomy-PK, medical-DSEK or medical-PK. Results Fifty eyes (30 DSEK, 20 PK) of 50 patients (mean age 77±10 years) met the enrolment criteria. Mean follow-up was 17.4±14.2 months. A significantly higher proportion of the DSEK grafts (50%) compared with PK grafts (10%) failed at last follow-up (p=0.005). Kaplan–Meier analysis identified a significant difference between the groups with respect to time to graft failure (p=0.006). Patients with trabeculectomy who underwent DSEK had earlier graft failures than all other groups (p≤0.035), but there were no differences between the medical-DSEK, medical-PK and trabeculectomy-PK groups (all p>0.35). Conclusions Eyes with prior glaucoma showed higher rates of DSEK graft failure compared with PK. Patients with prior trabeculectomy demonstrated higher and earlier corneal graft failure rates with DSEK than with PK.

We present a surgical technique in which polyethylene glycol hydrogel is used to seal corneal incisions and maintain air in the anterior chamber. This technique was used in 11 eyes that had Descemet-stripping endothelial keratoplasty (DSEK). In 2 cases, DSEK was combined with cataract extraction and intraocular lens implantation. In all cases, the anterior chamber was well formed with no leakage and the donor graft remained attached following surgery. The use of polyethylene glycol hydrogel in DSEK and combined DSEK–cataract surgery may shorten surgery, decrease suture-induced corneal astigmatism, and prevent the need for suture removal. Financial Disclosure Neither author has a financial or proprietary interest in any material or method mentioned.

To evaluate and compare the in vitro antimicrobial activity of levofloxacin versus ciprofloxacin and ofloxacin against ocular isolates from patients with bacterial conjunctivitis.The in vitro antimicrobial susceptibilities of ocular isolates to levofloxacin, ofloxacin, and ciprofloxacin were determined using both the agar disk diffusion and broth dilution methods.Disk diffusion susceptibility testing disclosed that 99% (100 of 101 isolates) of gram-negative isolates and 98% (127 of 129 isolates) of gram-positive isolates were susceptible to levofloxacin; 96% (97 of 101 isolates) of gram-negative isolates and 78% (100 of 129 isolates) of gram-positive isolates were susceptible to ofloxacin; and 94% (95 of 101 isolates) of gram-negative isolates and 61% (79 of 129 isolates) of gram-positive isolates were susceptible to ciprofloxacin. Broth dilution testing disclosed that 99% (72 of 73 isolates) of gram-negative isolates and 98% (111 of 113 isolates) of gram-positive isolates were susceptible to levofloxacin; 96% (70 of 73 isolates) of gram-negative isolates and 92% (104 of 113 isolates) of gram-positive isolates were susceptible to ofloxacin; and 95% (69 of 73 isolates) of gram-negative isolates and 82% (93 of 113 isolates) of gram-positive isolates were susceptible to ciprofloxacin.In this study, levofloxacin demonstrated superior in vitro activity against human bacterial conjunctival isolates compared with either ofloxacin or ciprofloxacin (levofloxacinofloxacinciprofloxacin).

Objective To investigate the role of matrix metalloproteinases (MMPs) in the pathogenesis of ulcerative keratolysis associated with topical use of generic diclofenac preoperatively and postoperatively. To characterize the inflammatory response of the cornea in this case of ulcerative keratolysis. Design Case report with clinicopathologic correlation. Main outcome measures Corneal culture for microbial growth. Clinical and histopathologic examinations including routine histolopathologic, immunofluorescent, and immunohistochemical studies. Results Microscopic examination of the corneal button disclosed fibrinous material with neutrophils and mononuclear inflammatory cells. The corneal epithelial basement membrane was irregularly thickened and patchy. Immunohistochemical staining detected weak staining of MMP-1 and a strong presence of MMP-8 in the epithelium. MMP-8 and 9 were also present in areas of leukocytic infiltration. MMP-2 appeared in a few stromal cells. Macrophages and leukocytes were the predominant infiltrating cells. Conclusions A nonspecific inflammatory response occurred in this case of ulcerative keratolysis. Corneal epithelial cells are capable of secreting MMP-1 and 8 and may participate in the stromal degradation and repair process of the ulcerative keratolysis associated with topical nonsteroidol antiinflammatory use.

To investigate the capability of cultivated allogeneic epithelial stem cells to restore a functional ocular surface in a limbal deficient cornea; to verify the long term survival of epithelial allograft; and to examine the host immune response to heterologous cell transplant in a rabbit model.Limbal deficiency was established by performing limbectomy on rabbits (n = 100). Corneal epithelial stem cells were obtained from the limbus and replicated in vitro without a supporting layer. The cell (3 x 10(5)) suspension was then transplanted via topical application as eye drops. Animals were divided into allograft, autograft, and control groups. Females were used as recipients and males as donors for the allograft. Corneas were collected at 7, 14, 21, 40 days as well as 2, 3, 7 and 8 months after cell transplantation. Experimental corneas were evaluated by histology, immunofluorescence, immunohistochemistry and Y chromosome analysis.A well-differentiated corneal epithelium was recognized at 14 to 40 days after cell transfer overlying an infiltrated corneal stroma. Corneal re-epitheliazation was confirmed in 31 of 36 allograft corneas. No significant immune rejection was noted. Stromal abnormality caused by previous limbal deficiency was mostly resolved three months after the regeneration of corneal epithelium.Transplanted corneal epithelial stem cells were able to differentiate into normal corneal epithelium in vivo without the use of membrane scaffolding. This non-autologous donor cell-derived corneal epithelium survived up to 8 months without immunosuppression and was able to reverse the stromal scarring. Thus, cultivated epithelial stem cells have great potential as an alternative to multiple-surgical procedures in the treatment of limbal deficiency states.

PURPOSE: Therapeutic soft contact lenses are used commonly as an adjunctive treatment after photorefractive keratectomy (PRK) to decrease postoperative pain caused by the movement of lids over the corneal epithelial defect and to facilitate epithelial healing. We assessed the microbiological profile of the conjunctiva of patients undergoing PRK for myopia, before and after the concurrent use of a therapeutic soft contact lens, and compared the effect on ocular bacterial colonization of prophylactic administration of topical tobramycin 0.3% versus ofloxacin 0.3%. METHODS: Forty-three consecutive eyes from 37 patients underwent PRK for myopia or myopic astigmatism. Eyes were assigned randomly to prophylactic antibacterial treatment with either topical ofloxacin 0.3% or tobramycin 0.3%, applied prior to surgery and three times daily after surgery until therapeutic soft contact lens removal. Material from the conjunctival sac was obtained for bacteriologic cultures prior to surgery. Clinical evaluation of all eyes was conducted prospectively. Three days after PRK, the therapeutic soft contact lenses were removed and cultured. Cultures from the conjunctival sac were then repeated. RESULTS: No statistically significant differences were observed in culture positivity between the two groups of eyes, in spite of some positive preoperative and postoperative cultures. Only one out of 43 eyes (assigned to the ofloxacin group) developed a peripheral corneal infiltrate. The corneal infiltrate healed completely without sequelae using antibiotic and corticosteroid therapy. CONCLUSIONS: The use of therapeutic soft contact lenses after PRK with either topical tobramycin 0.3% or ofloxacin 0.3% were well tolerated. However, perioperative positive conjunctival cultures were relatively frequent and prophylactic antibiotics should be used in the setting of an epithelial defect and therapeutic soft contact lens following PRK. [J Refract Surg 2001;17:55-62]

Purpose To report the management and outcome of late-onset traumatic dislocation of laser in situ keratomileusis (LASIK) flaps. Design Retrospective, observational case series. Participants Four patients with late-onset LASIK flap dislocation occurring after mechanical trauma at various intervals (10 days–2 months) after the procedure. Intervention In all cases of postoperative traumatic LASIK flap dislocation, the flap was refloated with scraping and irrigation of the underlying stromal bed within 12 hours of the injury. A bandage contact lens was placed, and a regimen including topical antibiotics and corticosteroids was instituted in all cases. Main outcome measures Best spectacle-corrected visual acuity and complications associated with the surgery were monitored. Results Postoperative follow-up ranged from 4 to 21 months. Nonprogressive epithelial ingrowth was noted in one patient and diffuse lamellar keratitis developed in another patient. All patients recovered pretrauma spectacle-corrected visual acuity. Conclusions Corneal LASIK flaps are prone to mechanical dislocation as late as 2 months after the procedure. Appropriate management results in recovery of optimal visual outcomes.

There have been no comprehensive investigations of striae after LASIK. The ophthalmic literature has few reports, and no one consistent therapy has been recommended. Striae are relatively uncommon; nevertheless, refractive surgeons need a systematic approach in prevention and therapy for striae. Careful flap handling and positioning can prevent many striae. Early recognition is very important and makes treatment significantly more likely to eliminate or reduce the striae. If the striae are identified within 24 hours, lifting and refloating will likely result in resolution of the striae. If the striae are more imbedded and have been present longer, additional techniques, such as those discussed, are helpful. New techniques will likely be developed because of an increase in lamellar procedures and an increase in the occurrence of striae.

Purpose To compare the efficacy of a single application of lidocaine 2% gel with tetracaine 0.5% drops for topical anesthesia in clear corneal cataract surgery. Setting The Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. Methods A preliminary toxicity study applied lidocaine 2% gel in the conjunctival fornices of rabbit eyes (n = 9). Biomicroscopic examination was performed and then enucleation at sequential intervals after the application. Intentional intracameral injection of lidocaine gel was performed (n = 3), followed by enucleation. Histopathological analysis was performed on all eyes. A randomized clinical trial comparing topical anesthesia in clear corneal cataract surgery was performed in 25 eyes of 25 patients (12 eyes randomly assigned to lidocaine gel, 13 eyes to tetracaine drops). Corneal sensation was measured with the Cochet–Bonnet aesthesiometer before application of the topical anesthesia, 5 minutes after application, and at the conclusion of surgery. Additional intraoperative local anesthesia and systemic sedation were recorded. Patients’ subjective level of comfort was reported 20 minutes after surgery, and the surgeon’s perception of patients’ comfort was also noted. Results In rabbits, lidocaine gel did not cause clinical or histopathological alteration of the ocular tissues. In the clinical study, median corneal sensitivity before application, after 5 minutes, and postoperatively was 6, 0, 0 (maximum sensitivity = 6), respectively, in the lidocaine gel group and 5, 0, 0, respectively, in the tetracaine drops group. Additional local anesthesia was administered in 17% and 31% of patients, respectively. Satisfactory comfort was reported by 58% in the lidocaine gel group and 62% in the tetracaine drops group. Conclusions A single application of lidocaine 2% gel was a safe and effective alternative to multiple topical anesthetic drops for clear corneal cataract surgery. Lidocaine 2% gel was similar to tetracaine drops in provision of corneal anesthesia and patient comfort,while causing no significant toxicity to the ocular surface.

The authors have identified a corneal stromal protein (CO-Ag) that may be involved in the pathogenesis of Mooren's ulcer. The CO-Ag cDNA sequence is identical to that of human neutrophil calgranulin C (CaGC). This study sought to demonstrate expression of the CaGC gene in the human cornea and in corneal keratocytes after cytokine stimulation. In situ hybridization and immunohistochemistry were used to localize CaGC mRNA and protein in normal and diseased human corneas, including a specimen with Mooren's ulcer. Cultured bovine keratocytes were stimulated with IL-1 alpha or TNF-alpha, and reverse transcription polymerase chain reaction (RT-PCR) was performed to amplify CaGC cDNA from cytokine-stimulated keratocytes and unstimulated controls. Southern blotting verified the specificity of the RT-PCR amplification products. In situ hybridization detected human CaGC mRNA in the stroma of corneas with Fuchs' dystrophy, postinfection corneas, and a cornea with Mooren's ulcer. In cultured bovine keratocytes, peak levels of CaGC mRNA were reached 6 h after cytokine stimulation. Southern blots with an oligonucleotide probe specific for CaGC detected the RT-PCR products of expected sizes (273 bp) and confirmed that the amplified CO-Ag sequence was identical to that of CaGC. These studies are the first to demonstrate the presence of CaGC in the human cornea and the ability of stromal keratocytes to produce CaGC (CO-Ag). The up-regulation of CaGC gene expression by corneal keratocytes due to proinflammatory cytokines from trauma or inflammation may induce autoimmunity that ultimately results in Mooren's ulceration.