Differential gene expression analysis of corneal endothelium indicates involvement of phagocytic activity in Fuchs' endothelial corneal dystrophy.

Fuchs' endothelial corneal dystrophy (FECD) is a progressive vision impairing disease caused by thickening of Descemet's membrane and gradual degeneration and loss of corneal endothelial cells. The aim of this study was to identify differentially expressed genes between FECD-affected and unaffected corneal endothelium to gain insight into the pathophysiological mechanisms underlying this disease. Microarray gene expression analysis was performed on total RNA from FECD-affected and unaffected corneal endothelium-Descemet's membrane (CE-DM) specimens using the Illumina HumanHT-12 v4.0 expression array. RNA from pools of FECD-affected (n = 3 per pool) and individual unaffected (n = 3) specimens was used for comparison. Altered expression of a sub-set of differentially expressed genes was validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in independent specimens. Bioinformatics analysis was performed using InnateDB to reveal functional relationships among the differentially expressed genes and molecular pathways involved in the disease. A total of 16,513 genes were found expressed in the corneal endothelium of which 142 genes were differentially expressed between FECD-affected and unaffected endothelium (log2 fold-change ≥1.5, corrected p-value ≤0.05). Most of the genes were up-regulated (126) and a small proportion down-regulated (16) in affected corneal endothelium. Of the twelve genes prioritised for validation, differential expression of 10 genes, including those ranked 57th and 81st by significance validated by qRT-PCR (8 up-regulated and 2 downregulated, corrected p ≤ 0.05), one gene showed a trend for up-regulation in affected endothelium, consistent with the microarray analysis and another was up-regulated in an independent study indicating robustness of the differential expression dataset. Bioinformatic analysis revealed significant over-representation of differentially expressed genes in extracellular matrix reorganisation, cellular remodelling, immune response, and inflammation. Network analysis showed functional inter-relatedness of the majority of the dysregulated genes and revealed known direct functional relationships between 20 of the genes; many of these genes have roles in macrophage differentiation, phagocytosis and inflammation. This is the second report of microarray gene expression analysis in FECD. This study revealed a set of highly dysregulated genes in the corneal endothelium in FECD. More than a third of the dysregulated genes in the disease have been discovered for the first time and thus are novel. The dysregulated genes strongly suggest the presence of phagocytic cells, most likely immune cells, and inflammation in corneal endothelium in the disease. This study provides a molecular framework for delineating the mechanisms underlying these cellular processes in FECD.

Risk factors and association with severity of keratoconus: the Australian study of Keratoconus.

SIGNIFICANCE: Our results show that asthmatic patients tend to have more severe KC and thus close monitoring for disease progression would be advised, and appropriate treatment strategies may be actioned stabilise the condition that may reduce the need for future corneal transplantation. PURPOSE: To explore a wide range of risk factors associated with the severity of keratoconus (KC). METHODS: A cross-sectional study of KC patients was undertaken in Melbourne, Australia. A questionnaire addressing age, gender, educational background, ocular and medical history, smoking and alcohol consumption, and physical examination comprising anthropometric measurements was collected; eye examination was undertaken. The associations between a range of risk factors and the severity of KC were determined using univariate and multivariable linear regression analyses. RESULTS: A total of 260 KC subjects were included in this study. Mean age of subject was 35.5 (SD = 14.8) years and the majority of the subjects were European 171 (68.2%). Initial univariate regression analysis identified the following risk factors at the p < 0.1 level with KC: higher body mass index, smoking cigarettes, diabetes, rheumatoid arthritis and asthma were associated with increased severity of KC, whereas eczema was associated with less severe KC. Following multivariable regression analysis, only asthma remained as a significant risk factor associated with 2.2 diopters (D) steeper average mean keratometry compared to KC subjects having no asthma [p = 0.03; ß = 2.18; 95% confidence intervals: 1.22, 4.14]. CONCLUSION: Our study describes the comprehensive assessment of all the known risk factors in a large KC cohort recruited in Australia. Our study has reported asthma as the only risk factor found to be significantly associated with the severity of KC. The results of this study allow us to better understand the aetiology of KC and such knowledge could be useful in instigate systemic management of patients to slow or prevent KC.

Accuracy of Intraocular Lens Power Formulas Modified for Patients with Keratoconus.

PURPOSE: To assess the accuracy of intraocular lens (IOL) power formulas modified specifically for patients with keratoconus (Holladay 2 with keratoconus adjustment and Kane keratoconus formula) compared with normal IOL power formulas (Barrett Universal 2, Haigis, Hoffer Q, Holladay 1, Holladay 2, Kane, and SRK/T). DESIGN: Retrospective consecutive case series. PARTICIPANTS: A total of 147 eyes of 147 patients with keratoconus. METHODS: Data from patients with keratoconus who had preoperative IOLMaster biometry were included. A single eye per qualifying patient was randomly selected. The predicted refraction was calculated for each of the formulas and compared with the actual refractive outcome to give the prediction error. Subgroup analysis based on the steepest corneal power measured by biometry (stage 1: ≤48 diopters [D], stage 2: >48 D and ≤53 D, and stage 3: >53 D) was performed. MAIN OUTCOME MEASURE: Prediction error. RESULTS: On the basis of the mean absolute prediction error (MAE), the formulas were ranked as follows: Kane keratoconus formula (0.81 D), SRK/T (1.00 D), Barrett Universal 2 (1.03 D), unmodified Kane (1.05 D), Holladay 1 (1.18 D), unmodified Holladay 2 (1.19 D), Haigis (1.22 D), Hoffer Q (1.30 D), and Holladay 2 with keratoconus adjustment (1.32 D). The Kane keratoconus formula had a statistically significant lower MAE compared with all formulas (P < 0.01). In stage 3 keratoconus, all nonmodified formulas had a hyperopic mean prediction error ranging from 1.72 to 3.02 D. CONCLUSIONS: The Kane keratoconus formula was the most accurate formula in this series. The SRK/T was the most accurate of the traditional IOL formulas. All normal IOL formulas resulted in hyperopic refractive outcomes that worsened as the corneal power increased. Suggestions for target refractive aims in each stage of keratoconus are given.

Reduced expression of apolipoprotein E and immunoglobulin heavy constant gamma 1 proteins in Fuchs endothelial corneal dystrophy.

BACKGROUND: Fuchs endothelial corneal dystrophy (FECD) is a progressive and potentially a sight threatening disease, and a common indication for corneal grafting in the elderly. Aberrant thickening of Descemet's membrane, formation of microscopic excrescences (guttae) and gradual loss of corneal endothelial cells are the hallmarks of the disease. The aim of this study was to identify differentially abundant proteins between FECD-affected and unaffected Descemet's membrane. METHODS: Label-free quantitative proteomics using nanoscale ultra-performance liquid chromatography-mass spectrometry (nUPLC-MSE ) was employed on affected and unaffected Descemet's membrane extracts, and interesting findings were further investigated using quantitative reverse transcription-polymerase chain reaction and immunohistochemical techniques. RESULTS: Quantitative proteomics revealed significantly lower abundance of apolipoprotein E (APOE) and immunoglobulin heavy constant gamma 1 protein (IGHG1) in affected Descemet's membrane. The difference in the distribution of APOE between affected and unaffected Descemet's membrane and of IGHG1 detected by immunohistochemistry support their down-regulation in the disease. Comparative gene expression analysis showed significantly lower APOE mRNA levels in FECD-affected than unaffected corneal endothelium. IGHG1 gene is expressed at extremely low levels in the corneal endothelium, precluding relative expression analysis. CONCLUSIONS: This is the first study to report comparative proteomics of Descemet's membrane tissue, and implicates dysregulation of APOE and IGHG1 proteins in the pathogenesis of Fuchs endothelial corneal dystrophy.

A randomized, controlled trial of corneal collagen cross-linking in progressive keratoconus: three-year results.

PURPOSE: To report the refractive, topographic, and clinical outcomes 3 years after corneal collagen cross-linking (CXL) in eyes with progressive keratoconus. DESIGN: Prospective, randomized controlled trial. PARTICIPANTS: One hundred eyes with progressive keratoconus were randomized into the CXL treatment or control groups. METHODS: Cross-linking was performed by instilling riboflavin 0.1% solution containing 20% dextran for 15 minutes before and during the 30 minutes of ultraviolet A irradiation (3 mW/cm(2)). Follow-up examinations were arranged at 3, 6, 12, 24, and 36 months. MAIN OUTCOME MEASURES: The primary outcome measure was the maximum simulated keratometry value (Kmax). Other outcome measures were uncorrected visual acuity (UCVA; measured in logarithm of the minimum angle of resolution [logMAR] units), best spectacle-corrected visual acuity (BSCVA; measured in logMAR units), sphere and cylinder on subjective refraction, spherical equivalent, minimum simulated keratometry value, corneal thickness at the thinnest point, endothelial cell density, and intraocular pressure. RESULTS: The results from 48 control and 46 treated eyes are reported. In control eyes, Kmax increased by a mean of 1.20±0.28 diopters (D), 1.70±0.36 D, and 1.75±0.38 D at 12, 24, and 36 months, respectively (all P <0.001). In treated eyes, Kmax flattened by -0.72±0.15 D, -0.96±0.16 D, and -1.03±0.19 D at 12, 24, and 36 months, respectively (all P <0.001). The mean change in UCVA in the control group was +0.10±0.04 logMAR (P = 0.034) at 36 months. In the treatment group, both UCVA (-0.15±0.06 logMAR; P = 0.009) and BSCVA (-0.09±0.03 logMAR; P = 0.006) improved at 36 months. There was a significant reduction in corneal thickness measured using computerized videokeratography in both groups at 36 months (control group: -17.01±3.63 µm, P <0.001; treatment group: -19.52±5.06 µm, P <0.001) that was not observed in the treatment group using the manual pachymeter (treatment group: +5.86±4.30 µm, P = 0.181). The manifest cylinder increased by 1.17±0.49 D (P = 0.020) in the control group at 36 months. There were 2 eyes with minor complications that did not affect the final visual acuity. CONCLUSIONS: At 36 months, there was a sustained improvement in Kmax, UCVA, and BSCVA after CXL, whereas eyes in the control group demonstrated further progression.

Assessment of anterior segment parameters of keratoconus eyes in an Australian population.

PURPOSE: To assess anterior segment parameters of eyes with keratoconus (KC) at different clinical stages of disease. METHODS: KC and non-KC patients were recruited from public and private clinics in Melbourne, Australia. Axial length (AL), mean front corneal curvature (Front Km), mean back corneal curvature (Back Km), central corneal thickness (CCT), corneal thickness at the apex (CTA), corneal thickness at the thinnest point (CTT), anterior chamber depth (ACD), and corneal volume were noted for all the eyes. RESULTS: A total of 181 individuals comprising 44 (24.3%) subclinical KC, 118 (65.2%) clinical KC, and 19 (10.5%) control subjects were analyzed. Significant differences were noticed between the subclinical KC and control group for ACD and CTT, whereas between clinical and control groups, significant differences were obtained for AL, CCT, CTA, CTT, and ACD (p < 0.05). In the case of mild, moderate, and severe KC groups, Back Km, CCT, CTA, and CTT were significantly associated (p < 0.001) with increasing disease severity. We further did receiver operating characteristic analysis to confirm the importance of pachymetric parameters in differentiating between control and KC eyes. The area under the receiver operating characteristic curve value of CTT for subclinical and clinical KC was 0.68 and 0.82, which showed that it may be a potential marker for the early detection and prevention of KC. CONCLUSIONS: This study identified the anterior chamber parameters that differ between subclinical and clinical KC as well as the severity of KC. There is a significant reduction in CTT between control and subclinical eyes, although there are no significant alterations in Front and Back Km or AL between the two groups. Also, a progressive reduction in the pachymetric readings at the pupil center, apex, and thinnest corneal point was identified when comparing mild to severe KC groups. Thus, corneal thickness represents an important parameter that needs to be considered in monitoring KC disease severity.

Localized changes in stromal reflectivity after corneal collagen cross-linking observed with different imaging techniques.

PURPOSE: To report changes observed in the corneal stroma using confocal microscopy and Scheimpflug imaging following epithelium-off collagen cross-linking (CXL) in cases of progressive keratoconus. METHODS: Fifteen eyes of 14 patients were examined before and after CXL using slit-lamp biomicroscopy, Scheimpflug imaging, and confocal microscopy. A subset of patients also had optical coherence tomography imaging performed. RESULTS: After CXL, confocal microscopy revealed a discrete layer of increased reflectivity in the mid to deep stroma. This layer was visible from as early as 1 week following treatment with patchy changes persisting until 12 months. This posterior reflective zone was found to consist of numerous linear or striate reflective structures (intrastromal striate reflections [ISRs]). ISRs were not observed in any of the eyes before the CXL procedure. High-resolution Scheimpflug and optical coherence tomography images also demonstrated a narrow zone of increased reflectivity at a similar depth. A layer-by-layer match was possible between the confocal and Scheimpflug images. The location of the ISR layer appears to correlate with a zone of increased reflectivity visible on postoperative slit-lamp examinations. CONCLUSION: Altered stromal reflectivity after CXL can be observed with modern diagnostic imaging technologies. These findings seem to correlate not only among the different devices but also with biomicroscopic observations and could potentially provide a non-invasive tool to monitor the cross-linking effect in individual corneas.

Collagen cross-linking: a new treatment paradigm in corneal disease - a review.

The last 2 years has seen a marked increase in the prominence of corneal collagen cross-linking as a treatment strategy for progressive keratoconus. This interest has arisen from a body of laboratory evidence documenting the biomechanical and cellular changes induced by cross-linking. The findings of this research provide a plausible rationale for its use in keratoconus to retard the progression of this common disease. The rapidly growing number of clinical reports suggests, not only a consistent stabilizing effect of cross-linking, but that a variable improvement in corneal shape and visual function may also occur in some patients. However, the marked variation in the clinical course of keratoconus, together with the challenges of accurately evaluating refractive error, visual acuity and even corneal shape in this condition, demands further evidence from randomized controlled clinical trials. The aim of this review is to summarize the theoretical basis and risks of corneal collagen cross-linking, along with the available evidence for its use in keratoconus and other corneal disease states.

A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results.

PURPOSE: This prospective, randomized, controlled trial aims to provide evidence in relation to the efficacy and safety of corneal collagen cross-linking (CXL) in the management of progressive keratoconus. METHODS: Eligible eyes were separately randomized into either treatment or control groups. Collagen crosslinking was performed using 0.1% riboflavin (in 20% dextran T500) and ultraviolet A (UVA) irradiation (370 nm, 3 mW/cm2, 30 min) in accordance with a previously published protocol. At each review, a full clinical ophthalmic examination was performed including endothelial cell count and confocal microscopy. RESULTS: To date, 66 eyes of 49 patients with documented progression of keratoconus have been enrolled and randomized. Interim analysis of treated eyes showed a flattening of the steepest simulated keratometry value (K-max) by an average of 0.74 diopters (D) (P = .004) at 3 months, 0.92 D (P = .002) at 6 months, and 1.45 D (P = .002) at 12 months. A trend toward improvement in best spectacle-corrected visual acuity was also observed. In the control eyes, mean K-max steepened by 0.60 D (P = .041) after 3 months, by 0.60 D (P = .013) after 6 months, and by 1.28 D (P < or = .0001) after 12 months. Best spectacle-corrected visual acuity decreased by logMAR 0.003 (P = .883) over 3 months, 0.056 (P = .092) over 6 months, and 0.12 (P = .036) over 12 months. No statistically significant changes were found for spherical equivalent or endothelial cell density. CONCLUSIONS: Preliminary results of this randomized controlled trial suggest a temporary stabilization of all treated eyes after CXL.

Atypical fungal sclerokeratitis.

PURPOSE: To report a case of fungal sclerokeratitis caused by Metarrhizium anisopliae, which to our knowledge is the first reported case worldwide. METHODS: A 52-year-old woman presented from rural Australia with a 1-week history of ocular injection involving the right eye without associated pain. Her best-corrected visual acuity was 6/9 in the right eye and 6/6 in the left eye. Intraocular pressure was 40 and 15 mm Hg in the right eye and left eye, respectively. On examination, a 7.0 x 4.5-mm area of corneal infiltrate and adjacent scleral necrosis involving the nasal limbus was evident. Cultures of corneal scrapings grew a filamentous fungus, identified as Metarrhizium anisopliae. The patient was started on multiple antifungal agents including topical natamycin, systemic and topical voriconazole, and eventually systemic and topical posaconazole. RESULTS: No significant response to antifungal agents over the course of a 25-day hospital admission was seen. A limbus-to-limbus therapeutic corneal graft was performed on eventual perforation. The patient developed multiple postoperative complications including cataract, hypotony, and a flat anterior chamber. Six months after initial presentation, her resulting visual acuity was hand motion, with evidence of early graft failure and hypotony; however, she was free of infection. CONCLUSIONS: Metarrhizium anisopliae is an extremely rare cause of ocular infection, and this report represents the first case of sclerokeratitis caused by this pathogen worldwide. Although found to be clinically sensitive to antifungal agents in previously reported cases of keratomycosis alone, it was found to be resistant to multiple antifungal agents with devastating consequences with the presence of scleral involvement.

Clinical efficacy of moxifloxacin in the treatment of bacterial keratitis: a randomized clinical trial.

PURPOSE: To determine the clinical efficacy and safety of moxifloxacin (1.0%) in patients with bacterial keratitis compared with patients treated with ofloxacin (0.3%) or fortified tobramycin (1.33%)/cephazolin (5%). DESIGN: Prospective randomized trial. PARTICIPANTS: A total of 229 patients diagnosed with bacterial keratitis were enrolled in the study; 78 patients were randomized to the fortified tobramycin/cephazolin group, 77 patients to the moxifloxacin group, and 74 patients to the ofloxacin group. A total of 225 patients were evaluable for safety and 198 patients were included in the efficacy analysis. INTERVENTION: After corneal specimens were obtained, the assigned study medication was instilled every hour, day and night, for 48 hours and on the third day, every hour by day and every 2 hours at night. For days 4 and 5, 1 drop every 2 hours by day and every 4 hours at night, and for days 6 and 7, 1 drop every 4 hours. After day 7, the antibiotic was tapered to every 6 hours and stopped when appropriate. MAIN OUTCOME MEASURES: Resolution of keratitis and healing of ulcer, time to cure, mean time to discharge, clinical sign score, adverse reactions to study medication, and treatment failures. RESULTS: Of the 186 nonexiting patients, resolution of the keratitis and healing of the ulcer occurred in 175 (94%) nonexiting patients. In the 175 patients in whom the corneal ulcer was cured, there were no statistically significant differences between the treatment groups for the mean time to cure (P = 0.25). There were no statistically significant differences between the 3 treatment groups in the various sign parameters including the sign score. A positive bacterial corneal culture was obtained in 190 (83%) of the 229 enrolled patients. The distribution of the species of bacterial organisms was similar in each treatment group and no significant difference in the percentage of isolates between the groups was observed. Twelve (5.2%) of the treated patients had serious complications (perforation or enucleation). No serious events attributable to therapy occurred during the study and all treatments were safe and well tolerated. CONCLUSION: No difference in healing rate, cure rate, or complications between fortified cephazolin and tobramycin, ofloxacin, or moxifloxacin was seen in this study.

Acanthamoeba keratitis and contact lens wear.

Acanthamoeba keratitis is a rare but serious complication of contact lens wear that may cause severe visual loss. The clinical picture is usually characterised by severe pain, sometimes disproportionate to the signs, with an early superficial keratitis that is often misdiagnosed as herpes simplex virus (HSV) keratitis. Advanced stages of the infection are usually characterised by central corneal epithelial loss and marked stromal opacification with subsequent loss of vision. In this paper, six cases of contact lens-related Acanthamoeba keratitis that occurred in Australia and New Zealand over a three-year period are described. Three of the patients were disposable soft lens wearers, two were hybrid lens wearers and one was a rigid gas permeable lens wearer. For all six cases, the risk factors for Acanthamoeba keratitis were contact lens wear with inappropriate or ineffective lens maintenance and exposure of the contact lenses to tap or other sources of water. All six patients responded well to medical therapy that involved topical use of appropriate therapeutic agents, most commonly polyhexamethylene biguanide and propamidine isethionate, although two of the patients also subsequently underwent deep lamellar keratoplasty due to residual corneal surface irregularity and stromal scarring. Despite the significant advances that have been made in the medical therapy of Acanthamoeba keratitis over the past 10 years, prevention remains the best treatment and patients who wear contact lenses must be thoroughly educated about the proper use and care of the lenses. In particular, exposure of the contact lenses to tap water or other sources of water should be avoided.

TGC repeat expansion in the TCF4 gene increases the risk of Fuchs' endothelial corneal dystrophy in Australian cases.

Fuchs' endothelial corneal dystrophy (FECD) is a progressive, vision impairing disease. Common single nucleotide polymorphisms (SNPs) and a trinucleotide repeat polymorphism, thymine-guanine-cytosine (TGC), in the TCF4 gene have been associated with the risk of FECD in some populations. We previously reported association of SNPs in TCF4 with FECD risk in the Australian population. The aim of this study was to determine whether TGC repeat polymorphism in TCF4 is associated with FECD in the Australian population. In 189 unrelated Australian cases with advanced late-onset FECD and 183 matched controls, the TGC repeat polymorphism located in intron 3 of TCF4 was genotyped using a short tandem repeat (STR) assay. The repeat length was verified by direct sequencing in selected homozygous carriers. We found significant association between the expanded TGC repeat (≥ 40 repeats) in TCF4 and advanced FECD (P = 2.58 × 10-22; OR = 15.66 (95% CI: 7.79-31.49)). Genotypic analysis showed that 51% of cases (97) compared to 5% of controls (9) were heterozygous or homozygous for the expanded repeat allele. Furthermore, the repeat expansion showed stronger association than the most significantly associated SNP, rs613872, in TCF4, with the disease in the Australian cohort. This and haplotype analysis of both the polymorphisms suggest that considering both the polymorphisms together rather than either of the two alone would better predict susceptibility to FECD in the Australian population. This is the first study to report association of the TGC trinucleotide repeat expansion in TCF4 with advanced FECD in the Australian population.

Microbial keratitis predisposing factors and morbidity.

PURPOSE: To examine predisposing factors, treatment costs, and visual outcome of microbial keratitis in an ophthalmic casualty and inpatient population. DESIGN: Retrospective medical records review. PARTICIPANTS: Fifteen- to 64-year-olds with microbial keratitis treated at the Royal Victorian Eye and Ear Hospital between May 2001 and April 2003 (n = 291). METHODS: Risk factors were identified from patient files. Demographic, clinical, and microbiological data; severity; outpatient visits; hospital bed days; and vision loss were examined. MAIN OUTCOME MEASURES: Cost to treat (Australian dollars), vision loss, and factors influencing these outcomes. RESULTS: Ocular trauma (106/291 [36.4%]) and contact lens (CL) wear (98/291 [33.7%]) were the most commonly identified predisposing factors; 18 (6.1%) had multiple predisposing factors; 17 (5.8%), ocular surface disease; 20 (6.9%), herpetic eye disease; 4 (1.4%), systemic associations; 5 (1.7%), other; and 23 (7.9%), unknown cause. Of trauma cases, 90.6% involved males, compared with 44% to 57% for other groups (P<0.001). Contact lens wearers were younger than the other groups--mean age 30 years, compared with 40 to 47 years (P<0.01). Gram-negative organisms were isolated more frequently in CL wearers than trauma cases (18.7% vs. 6.5%, P = 0.01). The number of outpatient visits was 4+/-1 (median +/- interquartile range), and 19.6% (57/291) were hospitalized for 5+/-2 days. Hospital resource use and vision loss were similar for predisposing factors but differed by causative microorganism. Eighty-eight percent of cases were scraped: acanthamoeba keratitis was the most expensive to treat, followed by fungal and herpetic keratitis and, lastly, culture-proven bacterial keratitis or culture-negative cases (P<0.0001). After treatment, 21.7% exhibited >2 lines of vision loss, and 1.6% of cases had > or =10 lines of vision loss. Vision loss was associated with clinical severity (P = 0.005). CONCLUSIONS: Ocular trauma and CL wear are the major predisposing factors for microbial keratitis in this age range. These cases require significant hospital resources during treatment, and the keratitis may result in loss of vision.

Outcomes of implantation of an artificial cornea, AlphaCor: effects of prior ocular herpes simplex infection.

PURPOSE: To review outcomes of AlphaCor artificial cornea implantation in patients with and without a history of ocular herpes simplex virus (HSV) and to determine whether herpetic eye disease is an indication for AlphaCor surgery. METHODS: Outcomes of the initial 40 implantations were reviewed and stratified by the presence of a history of ocular disease caused by HSV. Outcomes measures (complications, visual acuity gained) were compared. RESULTS: Eight of the 40 AlphaCor implantations (20%) were in patients with a history of ocular HSV. Six of these eight patients (75%) developed melt-related complications after AlphaCor insertion. Half of the affected patients required removal of the AlphaCor and replacement with a donor corneal graft to restore ocular integrity. In comparison, only six of the 32 (18.8%) patients without HSV developed a melt after AlphaCor insertion. Patients with HSV with devices in situ exhibited a mean loss of 0.3 line of best-corrected visual acuity compared with the preoperative visual acuity, whereas patients without HSV exhibited a mean gain of 1.4 lines of best-corrected visual acuity. CONCLUSIONS: The extensive lamellar corneal surgery involved in AlphaCor implantation may precipitate reactivation of latent HSV such that reactivation and resultant inflammation reduce device biointegration and facilitate melting of corneal stromal tissue anterior to the device. Although there may be some benefit from systemic antiviral medication, the current series is not large enough to demonstrate such a benefit, and melting can occur despite medication. The statistically significant difference in outcomes between recipients of AlphaCor with and without HSV is evidence that a history of HSV should be an exclusion factor for AlphaCor surgery.

AlphaCor cases: comparative outcomes.

PURPOSE: To describe clinical outcomes after a novel type of corneal surgery, implantation of an artificial cornea, AlphaCor , and to evaluate outcomes in comparison with alternative keratoprostheses and high-risk grafts. METHODS: Case reports and data from a noncontrolled clinical trial and a literature review. RESULTS: The probability of AlphaCor retention to 1 year is 80%. Postoperative best corrected visual acuity ranges from Perception Light to 20/30. The most significant complications are stromal melts and optic depositions, for both of which the main risk factors have been identified. Complications can be managed without loss of the eye. CONCLUSION: Results from the clinical trial period have helped to determine the indications and risk factors for AlphaCor surgery and to refine surgical techniques. Continued monitoring of outcomes as the series increases will allow a more accurate determination of comparative outcomes. The series provides preliminary evidence that AlphaCor may have a lower incidence of complications than traditional keratoprostheses and may prove to be preferable to a donor graft in high-risk cases.

Treatment of infectious keratitis with riboflavin and ultraviolet-A irradiation.

UNLABELLED: We report 4 eyes with infectious keratitis treated with riboflavin/ultraviolet-A irradiation (corneal collagen crosslinking [CXL]) in addition to medical treatment. In 2 eyes with bilateral keratitis, the fellow eye was treated with medical treatment alone. The other 2 eyes had refractory keratitis. The results suggest that CXL may be more worthwhile in cases refractory to conventional medical treatment. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

A randomised controlled trial of alcohol delamination and phototherapeutic keratectomy for the treatment of recurrent corneal erosion syndrome.

AIM: To compare the efficacy of alcohol delamination (ALD) and phototherapeutic keratectomy (PTK) for the treatment of recurrent corneal erosion syndrome (RCES) in a prospective, randomised, controlled trial. METHODS: Patients with RCES not responding to conservative treatment were recruited and randomised to undergo ALD or PTK. Patients were masked to their treatment group. The primary outcome measure was the intensity of pain on waking, using a numerical rating scale between 0 and 10 to record a subjective pain score. RESULTS: 17 eyes were treated with ALD and 16 eyes were treated with PTK. The mean follow-up period was 16.25 and 17.25 months, respectively. There were no differences in baseline parameters or pain scores at 3, 6, 12 and 24 months between the groups. The pain score improved from baseline at 3 months (ALD, p=0.022; PTK, p=0.014) and 6 months (ALD, p=0.033; PTK, p=0.036) in both groups, but only in the ALD group at 24 months (ALD, p=0.035; PTK, p=0.500). Overall, there was complete or partial resolution of symptoms in 11 (65%) eyes in the ALD group and 10 (63%) eyes in the PTK group. Recurrence of symptoms was observed in five eyes in the ALD group and six eyes in the PTK group. There was one treatment failure in the ALD group. There were no long-term complications. CONCLUSIONS: ALD should be considered as an alternative treatment for the management of RCES with promising results compared with PTK.