Effects of amniotic membrane extract on primary human corneal epithelial and limbal cells.

BACKGROUND: To assess the effects of amniotic membrane extract (AMX) on cellular activity of primary human corneal epithelial (HCE) cells under mechanical and oxidative stress, and on human limbal cells under oxidative stress. METHODS: Corneal mechanical stress was simulated with a linear scratch in confluent HCE cell plates, then incubated with 0.1% AMX for 48 and 72 h. Subjecting HCE cultures to 0.5 mmol/L tertiary-butylhydroperoxide for 1 h simulated an oxidative stress. 0.1% AMX-treated cultures were compared with controls at 24 and 48 h using cellular viability assay, along with 12-h AMX pretreatment and human limbal cell comparisons. RESULTS: Mechanical stress on HCE cultures revealed a statistically significant distance ratio at 48 and 72 h in favour of 0.1% AMX-treated cultures (P = 0.021 and 0.035, respectively). Oxidative stress did not reveal any significant difference in cellular viability of AMX-treated versus control cultures. Twelve hour AMX pre-treatment prior to oxidative stress revealed a significant difference after 24 h from oxidative injury (73.3% AMX vs. 66.0% control, P = 0.035), but not after 48 h. Human limbal cells demonstrated significantly improved oxidative viability compared with HCE cells, with (91.0% vs. 82.0% control, P = 0.017) and without 0.1% AMX pre-treatment (91.2% vs. 83.7% control, P = 0.019). CONCLUSIONS: HCE cells treated with AMX healed faster after mechanical insult, suggesting a potential benefit in acute corneal injuries. Under oxidative stress, human limbal cells, a more proliferative cell type, showed superior viability compared with HCE cells.

IC3D Classification of Corneal Dystrophies-Edition 3.

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 .

Novel Application of Conjunctival Anterior Segment Optical Coherence Tomography Angiography to Assess Ocular Redness.

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.

Efficacy and Safety of the Melanocortin Pan-Agonist PL9643 in a Phase 2 Study of Patients with Dry Eye Disease.

Purpose: The melanocortin receptor pan-agonist PL9643, a potential therapy for ocular diseases, was investigated in a phase 2, 12-week study in patients with dry eye disease (DED). Methods: This was a placebo-controlled study evaluating efficacy and safety of thrice-daily PL9643. Placebo (vehicle) was similar to tears. Primary endpoints were intra-patient changes in inferior corneal fluorescein staining and ocular discomfort after 12 weeks. Secondary endpoints were changes in additional DED signs or symptoms. Multiple secondary endpoints were not adjusted for multiplicity. Patients with moderate or severe DED were analyzed in addition to the overall intent-to-treat (ITT) population. Results: In the ITT population (n = 160) the PL9643 group did not demonstrate significant treatment difference versus placebo at week 12/day 85 for the primary endpoints (P > 0.05). In patients with moderate or severe DED (n = 53), PL9643 treatment demonstrated either nominally significant (P < 0.05) or trending (P < 0.1) improvement over placebo in mean change from baseline at week 12/day 85 in several sign endpoints, including fluorescein staining in inferior, superior, corneal sum, and total sum regions; Lissamine Green staining in temporal, nasal, conjunctival sum, and total sum regions; and tear film breakup time. Conjunctival redness also showed (nonsignificant) improvement at week 12/day 85. There were no drug-related adverse events (AEs) and no drug-related discontinuations. Conclusions: PL9643 showed no significant efficacy for the ITT population; however, efficacy results across several signs and symptoms in the subpopulation of moderate to severe DED patients, the low number of ocular AEs, and no tolerability issues suggest that PL9643 shows promise as a therapeutic for DED. Clinical Trial Registration number: NCT04268069.

Comment on "Cornea Classic Article: Kim JC and Tseng SCG: Transplantation of Preserved Amniotic Membrane for Surface Reconstruction in Severely Damaged Rabbit Corneas (Cornea 1995;14:473-484)".

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.

Acute Corneal Transplant Rejection After COVID-19 Vaccination.

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.

Efficacy of a hinged pupil expansion device in small pupil cataract surgery.

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.

Novel Parameters to Assess the Severity of Corneal Neovascularization Using Anterior Segment Optical Coherence Tomography Angiography.

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 mm3 to 1.0 ± 0.3 mm3, P = .025, respectively) and from moderate to severe CoNV (44.6 ± 5.3%, P < .001, and 2.0 ± 0.3 mm3, P = .014, respectively). CoNV area and posterior limit increased from mild to moderate (1.7 ± 0.3 mm2 to 4.6 ± 0.7 mm2, 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.

The utility of anterior segment optical coherence tomography angiography for the assessment of limbal stem cell deficiency.

PURPOSE: To determine the utility of anterior segment optical coherence tomography angiography (AS-OCTA) in assessing limbal stem cell deficiency (LSCD). METHODS: Twenty-six eyes of 24 LSCD patients, classified clinically into stage I, II and III, and 12 eyes of 12 healthy subjects were included. AS-OCTA images were analyzed by two masked observers, measuring the maximum corneal vascular extension (CoVE) from the limbus to the furthest vessel over the cornea, and corneal vascular thickness (CoVT) from the most superficial to the deepest corneal vessel. RESULTS: CoVE was 0.27 ± 0.10, 0.79 ± 0.21, 1.68 ± 0.89 and 2.53 ± 0.82 mm in controls, stage I, II and III LSCD, respectively (p < 0.001). The CoVT was 51.0 ± 19.4, 113.7 ± 36.6, 129.7 ± 39.3 and 336.0 ± 85.0 µm, respectively (p < 0.001). There was a significant difference in CoVE and CoVT between all stages compared to controls, and between stage I and III LSCD (p < 0.001). Further, CoVE showed a significant difference between stage I and II, whereas CoVT showed a significant difference between stage II and III LSCD (p < 0.001). BCVA showed strong correlation with CoVT (r = 0.765, p < 0.001) and moderate correlation with CoVE (r = 0.547, p = 0.001). AS-OCTA parameters showed excellent intra- and inter-class correlation coefficients (>0.900). CONCLUSION: LSCD demonstrates significant changes in CoVE and CoVT as early as stage I LSCD in comparison to controls. CoVE and CoVT strongly correlate to both disease severity and BCVA. AS-OCTA may provide novel quantitative and non-invasive parameters to assess LSCD.

Years-needed-to-treat to add 1 year of life: a new metric to estimate treatment effects in randomized trials.

AIMS: A standard metric to estimate absolute treatment effects is numbers-needed-to-treat (NNT), which implicitly assumes that all benefits reverse at trial-end. However, in-trial survival benefits typically do not reverse until long after trial-end, so that NNT will substantially underestimate lifetime benefits. METHODS AND RESULTS: We developed a new concept, years-needed-to-treat (YNT) to add 1 year of life, that quantifies the expected average life expectancy for two treatments including the estimated years of life remaining post-trial. Numbers-needed-to-treat and YNT were calculated in the COMET trial, in which carvedilol vs. metoprolol tartrate resulted in 17% lower mortality over 4.8 years. A multivariate Cox model was used to predict survival. Remaining years of life were estimated using the mortality-life-table method. At trial-end, survival was 9% higher in the carvedilol arm. Assuming that patients remained on the same therapy post-trial, the average total years of life for carvedilol vs. metoprolol were 10.63 +/- 0.19 vs. 9.48 +/- 0.18 (P < 0.0001) or 1.15 (95% confidence interval 0.64-1.66) additional years of life. The YNT was 9.2, indicating that 9.2 person-years of treatment added 1 person-year of life, compared with NNT of 59. CONCLUSION: Compared with NNT, the YNT method more accurately accounts for potential long-term benefits of interventions in randomized trials.

Clevidipine: an ultra short-acting calcium channel antagonist for acute hypertension.

OBJECTIVE: To review the safety, efficacy, and pharmacologic characteristics of clevidipine, a new ultra short-acting intravenous antihypertensive agent for the treatment of moderate-to-severe hypertension. DATA SOURCES: A literature search was conducted through MEDLINE (1966-March 2009), International Pharmaceutical Abstracts (1970-March 2009), and EMBASE (1988-March 2009) using the search terms clevidipine, H324/38, hypertension, and hypertensive crisis. STUDY SELECTION AND DATA EXTRACTION: Available studies, abstracts, and review articles published in English that evaluated the pharmacology, pharmacokinetics, safety, and clinical efficacy of clevidipine were reviewed and critically evaluated. DATA SYNTHESIS: Clevidipine is a new third-generation dihydropyridine calcium-channel blocker available for intravenous management of moderate-to-severe hypertension. Clevidipine is an ultra short-acting, selective arteriolar vasodilator that acts similar to other L-type dihydropyridine calcium-channel blockers by inhibiting influx of extracellular calcium into the vascular smooth muscle. Its safety and efficacy have been primarily evaluated in the perioperative setting in patients undergoing cardiac surgery requiring management of elevated blood pressure. In comparison to most other intravenous antihypertensives, clevidipine has a rapid onset of action, is ultra short-acting, easily titratable with a predictable dose response, and is void of drug-drug interactions and need for dose adjustment in patients with hepatic or renal insufficiency, thus making it a valuable antihypertensive in both the intraoperative and critical care settings. In clinical trials, clevidipine was well tolerated at infusion rates from 2-32 mg per hour, for up to 72 hours. CONCLUSIONS: Clevidipine is the first intravenous antihypertensive approved by the Food and Drug Administration in nearly a decade. Based on available published clinical trials, clevidipine appears to be safe and effective in the acute management of moderate-to-severe elevations in blood pressure and a viable alternative to other agents such as nitroglycerin, sodium nitroprusside, and nicardipine.

Discrepancies in identification of major bleeding events in patients taking warfarin.

STUDY OBJECTIVE: To assess the level of agreement between one subjective definition of major bleeding (criteria A) and two objective definitions: the International Society on Thrombosis and Haemostasis ([ISTH] criteria B) and the Italian Study of Complications of Anticoagulant Therapy ([ISCOAT] criteria C). DESIGN: Retrospective cohort study. SETTING: Four anticoagulation clinics at a university-affiliated medical center. PATIENTS: One hundred twenty patients aged 21-96 years who were taking long-term warfarin therapy and experienced a nonminor bleeding event between July 1, 2001, and June 30, 2006. MEASUREMENTS AND MAIN RESULTS: Bleeding events were evaluated using three definitions of major bleeding: criteria A-event was fatal or required hospitalization; criteria B-event was fatal, was symptomatic in a critical area or organ, caused a decrease in hemoglobin level of 2 g/dl or more, and/or led to transfusion of 2 or more units of whole blood or red blood cells; and criteria C-event met criteria B definition (but less inclusively identifies critical areas or organs) and/or necessitated surgical or angiographic intervention. One hundred thirty-eight bleeding events in the 120 patients met at least one of the definitions of major bleeding and thus were included in the analysis. Level of agreement among the definitions was determined by the kappa statistic. The level of agreement between criteria B and C was excellent; no discrepancies were found; however, the level of agreement between criteria A and criteria B or C was poor, with a kappa statistic value of -0.134 (95% confidence interval -0.196 to -0.071). Use of criteria A resulted in underreporting of 31 major bleeding events by excluding events that were managed on an outpatient basis. CONCLUSION: The discrepant event rates determined by using three different definitions of major bleeding underscore the need for implementation of a standardized objective definition. Use of a standardized definition in clinical trials to accurately predict and compare patient outcomes and in clinical practice as a marker for patient safety will increase quality of care and decrease total costs of care in patients treated with warfarin. We suggest implementation of the ISTH criteria in clinical practice as a method to standardize the reporting of major bleeding events.

Modeling Diabetic Corneal Neuropathy in a 3D In Vitro Cornea System.

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.

Colocalization of Galectin-3 With CD147 Is Associated With Increased Gelatinolytic Activity in Ulcerating Human Corneas.

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.

Human Corneal Tissue Model for Nociceptive Assessments.

New in vitro tissue models to mimic in vivo conditions are needed to provide insight into mechanisms involved in peripheral pain responses, potential therapeutic strategies to address these responses, and to replace animal models for such indications. For example, the rabbit cornea Draize test has become the standard method used for decades to screen ophthalmic drug and consumer product toxicity. In vitro tissue models with functional innervation have the potential to replace in vivo animal testing and provide sophisticated bench tools to study ocular nociception and its amelioration. Herein, full thickness, innervated, 3D human corneal tissues are grown under physiologically relevant culture conditions to study nociceptive-related responses, by mimicking ocular environmental cues, including intraocular pressure (IOP) and tear flow (TF). Capsaicin, a chili pepper-derived irritant known to cause a burning sensation in mammalian tissues is utilized as a nociceptive stimulant to induce pain, while subsequent serum treatment is used to mimic healing. Pain mediators released upon capsaicin stimulation and cell regrowth after serum treatment are characterized to assess ocular responses in this new, innervated, human corneal tissue system for comparison of outcomes to established animal and related responses.

Chemical Burns of the Eye: The Role of Retinal Injury and New Therapeutic Possibilities.

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.

Incidence and clinical features of ganciclovir-resistant cytomegalovirus disease in heart transplant recipients.

BACKGROUND: The incidence and clinical and virologic aspects of ganciclovir-resistant cytomegalovirus (CMV) disease have not been well-characterized in heart transplant recipients. METHODS: We retrospectively analyzed all patients who underwent their first heart transplantation during the period from 1 January 1995 through 30 June 2005 at a single health care center. Cox proportional hazard regression was used to assess the relationship between clinical variables and CMV disease. Portions of the UL97 gene were sequenced in patients with slow clinical and/or virologic response to ganciclovir therapy. RESULTS: Cytomegalovirus disease developed in 32 (11.7%) of 274 patients at a median of 4.2 months after transplantation (range, 1.8-11.6 months after transplantation) and was independently associated with donor-seropositive/recipient-seronegative (D+/R-) serostatus (adjusted hazard ratio, 6.93; P<.001). The incidence of ganciclovir-resistant CMV disease was 1.5% overall (4 of 274 patients), 5% among D+/R- serostatus recipients (4 of 80 patients), and 12.5% among patients who developed CMV disease (4 of 32 patients). Ganciclovir-resistant CMV disease was significantly associated with D+/R- serostatus (4 [5%] of 80 vs. 0 [0%] of 153 patients; P=.02), greater prior exposure to ganciclovir (median duration of exposure, 150 vs. 69 days; P=.003), and substantial morbidity, including prolonged CMV-associated hospitalization (median duration of hospitalization, 66 vs. 0 days; P<.01). CONCLUSIONS: CMV disease, including ganciclovir-resistant disease, is an important clinical problem in D+/R- heart transplant recipients who receive antiviral prophylaxis. Strategies specifically designed to reduce the incidence and impact of CMV disease in this population are warranted.

Aqueous Humor Penetration and Biological Activity of Moxifloxacin 0.5% Ophthalmic Solution Alone or with Dexamethasone 0.1.

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.

Clinical profile and early surgical complications in the Cornea Donor Study.

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.

Laser in situ keratomileusis outcomes following radial keratotomy, astigmatic keratotomy, photorefractive keratectomy, and penetrating keratoplasty.

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.