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Significant restoration of visual function can occur following pituitary tumor resection, although the time course of visual recovery remains poorly understood. This single-centre, two-year, prospective cohort study investigated the temporal patterns of visual recovery in consecutive patients undergoing pituitary tumor resection, between 2009 and 2018. Eyes were stratified based on pre-operative optical coherence tomography (OCT) retinal nerve fibre layer (RNFL) thickness measurements, with thin RNFL being defined as those within the fifth-percentile of age-matched normative values, and normal RNFL as those above the fifth-percentile. Visual function and OCT parameters were assessed pre-operatively, and at 6 weeks, 6 months, and 2 years post-operatively. 456 eyes of 228 patients (mean ± SD age, 53 ± 15 years) were included, of which 114 (25%) eyes had thin RNFL pre-operatively. Visual field recovery was observed in both groups during the first 6 weeks post-operatively (all Q ≤ 0.02), although improvements in visual field parameters between 6 weeks to 6 months were limited to eyes with thin RNFL (both Q 0.05). No further improvements in visual function were detected beyond 6 months in both groups (both Q 0.50). Similar trends were observed in linear regression analysis according to baseline visual function in both groups. In summary, eyes with normal RNFL thickness at baseline experienced most of their recovery within the first six weeks following surgery, while eyes with thin RNFL exhibited gradual improvements during the first six months. These findings have important implications when providing patient counselling and prognostication in the pre-operative setting.

Keratoconus is a potentially blinding condition that slowly deforms the cornea in young people. Despite the increasing prevalence of keratoconus, the exact aetiology of the condition is unknown. This first systematic review examines the evidence of eye rubbing and its association with keratoconus and presents the findings of the meta-analysis. Two independent reviewers searched the electronic databases for all potential articles published from 1st of January 1900 to 31st of July 2020 on eye rubbing and keratoconus. The researchers assessed the methodological quality of the studies using the Newcastle-Ottawa scale for observational studies. The assessment for statistical heterogeneity was estimated using chi-square and I-square (I2) tests. A p value of

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. To explore a wide range of risk factors associated with the severity of keratoconus (KC). 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. 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

Endothelial keratoplasty (EK) is increasingly used to treat corneal endothelial disease. However, issues remain with EK including a non-zero rejection rate, shortage of donor tissue, and technical challenges for Descemet’s membrane endothelial keratoplasty. Technologies that might solve these issues include small-molecule drugs, surgical innovations, cell therapy, tissue engineering, and gene therapy. Our purpose is to inform ophthalmologists, eye bankers, and eye health professionals of technologies that could impact practice in the near future. Recent advances are targeted at solving known issues with EK. Although none is yet routine, some are in clinical trials. Technologies that are closest to an ideal solution are those facing the highest regulatory and commercial hurdles. In the future, there will multiple options for the treatment of corneal endothelial cell failure. Which of these differing treatments will be used will depend on their efficacy as well as commercial, regulatory, and patient factors.

IMPORTANCE: This is the first study to estimate the lifetime costs associated with keratoconus based on a questionnaire completed by patients and highlights the significant economic burden of the disease. As keratoconus affects individuals from a young age, the study highlights keratoconus as a public health concern. BACKGROUND: Keratoconus is a disorder characterised by corneal steepening and thinning, leading to reduced visual acuity. To date, there have been no studies evaluating the economic costs of keratoconus from a patient's perspective. DESIGN: A randomised cross-sectional study undertaken in Australia where keratoconus subjects were recruited from public and private ophthalmology and optometry clinics. PARTICIPANTS: A total of 100 participants completed the questionnaire: median age was 31 years and 57% were males. METHODS: A keratoconus health expenditure questionnaire was designed to assess direct and indirect expenditures for each individual. MAIN OUTCOME MEASURES: Total direct and indirect costs associated with the condition were calculated along with the estimated lifetime per capita costs. RESULTS: The total cost related to direct and indirect care was estimated to be AUD 3365. By applying our cost data to keratoconus prevalence data for the Australian population, the total cost is estimated to be approximately AUD 44.7 million per year in Australia. CONCLUSIONS AND RELEVANCE: Our results show that the costs associated with the diagnosis and management of keratoconus represent a significant cost to patients. An understanding of this is important not only to individuals and their families, but also health care providers, health insurers and the wider health system. This article is protected by copyright. All rights reserved.

To investigate association between keratoconus and allergic eye diseases, eye rubbing, and atopy.PubMed, Web of Science, Scopus, and Cochrane were searched for relevant published studies from inception to April 2021 without restrictions or filters. We included case-control, cohort, and cross-sectional studies that investigated eye allergy, atopy, or eye rubbing as possible risk factors for KC. Two authors independently screened all titles and abstracts against predefined inclusion and exclusion criteria. This study analysed keratoconus prevalence and risk factors including eye rubbing, family history of keratoconus, atopy, and allergic eye diseases. The National Institute of Health Study Quality Assessment tool was utilised. Pooled data were presented as odds ratio (OR) and 95% confidence intervals (CI). Analysis was conducted using RevMan version 5.3 software.Out of 573 articles, we excluded 161 duplicates than 361 articles by title and abstract screening. The remaining 51 articles underwent full-text screening, and 29 articles were excluded. Twenty-one studies were included in the qualitative synthesis and fifteen for quantitative synthesis. There was no significant association found between KC and allergic eye diseases (OR = 1.03, 95% CI [0.96, 1.11], p = 0.45), eye rubbing (OR = 1.59, 95% CI [0.70, 3.63], p = 0.27), or atopy (OR = 1.08, 95% CI [0.80, 1.44], p = 0.62).No significant association was observed between KC and allergic eye disease, eye rubbing, or atopy. Further prospective studies are needed to clarify and validate these findings.

Keratoconus is a potentially blinding condition that slowly deforms the cornea in young people. Despite the increasing prevalence of keratoconus, the exact aetiology of the condition is unknown. This first systematic review examines the evidence of eye rubbing and its association with keratoconus and presents the findings of the meta-analysis.Two independent reviewers searched the electronic databases for all potential articles published from 1st of January 1900 to 31st of July 2020 on eye rubbing and keratoconus. The researchers assessed the methodological quality of the studies using the Newcastle-Ottawa scale for observational studies. The assessment for statistical heterogeneity was estimated using chi-square and I-square (IEight case-control studies were included in this systematic review. Two studies assessed eye rubbing without odds ratios and thus were excluded. The pooled odds ratios for the six remaining studies included in the meta-analysis was 6.46 (95% CI 4.12-10.1). The study results were heterogenous (IEye rubbing showed consistent association with keratoconus. However, the current evidence is limited to only a small number of case-control studies which present as heterogeneous and of sub-optimal methodological quality. Additionally, the cause-effect temporal relationship cannot be determined. Further studies are needed to address this intricate relationship of eye rubbing and its induction, ongoing progression, and severity of keratoconus.

The complexity of dynamic global markets, accelerated change and the new pressures placed on businesses today have fundamentally reshaped the process and content of successful strategy.

Mitochondrial haplogroups H1, H2 and UK have previously been reported to be associated with proliferative diabetic retinopathy (PDR) in Caucasian patients with diabetes. We aimed to replicate this finding with a larger sample and expand the analysis to include different severities of DR, and diabetic macular edema (DME). Caucasian participants (n = 2935) with either type 1 or type 2 diabetes from the Australian Registry of Advanced Diabetic Retinopathy were enrolled in this study. Twenty-two mitochondrial single nucleotide polymorphisms were genotyped by MassArray and haplogroups reconstructed using Haplogrep. Chi square tests and logistic regressions were used to test associations between haplogroup and DR phenotypes including any DR, non-proliferative DR (NPDR), proliferative DR (PDR) and DME. After stratifying the samples in type 1 and type 2 diabetes groups, and adjusting for sex, age, diabetes duration, concurrent HbA1c and hypertension, neither haplogroups H1, H2, UK, K or JT were associated with any DR, NPDR, PDR or DME.

PURPOSE: To investigate the association between optical coherence tomography (OCT) parameters and long-term visual recovery following optic chiasm decompression surgery. DESIGN: Prospective cohort study. METHODS: Consecutive patients who underwent pituitary or parasellar tumor resection between January 2009 to December 2018 were recruited in a single-center, 2-year prospective, longitudinal cohort study. Best-corrected visual acuity, visual fields, and OCT retinal nerve fiber layer (RNFL) thickness, macular thickness and volume were assessed preoperatively, and at 6 weeks, 6 months, and 2 years postoperatively. Long-term visual field recovery and maintenance were defined as a mean deviation of >-3 at 24 months, and visual acuity recovery and maintenance were defined as a logarithm of minimal angle of resolution (logMAR) of 0 (Snellen 20/20) or better at 24 months. RESULTS: A total of 239 patients (129 men, 110 women; mean ± SD age: 52 ± 16 years) were included. Multiple logistic regression analysis demonstrated that increased inferior RNFL thickness (per 10 μm) was associated with higher odds of long-term visual field recovery and maintenance (odds ratio [OR]: 1.26; 95% confidence interval [CI]: 1.12-1.41; Q < 0.001), and greater superior RNFL thickness (per 10 μm) was associated with higher odds of visual acuity recovery and maintenance (OR: 1.13; 95% CI: 1.03-1.27; Q = 0.031). A multivariable risk prediction model developed for long-term visual field recovery and maintenance that incorporated age, preoperative visual function, and RNFL thickness demonstrated C-statistics of 0.83 (95% CI: 0.72-0.94). CONCLUSION: Preoperative RNFL thickness was associated with long-term visual recovery and maintenance following chiasmal decompression. The multivariable risk prediction model developed in the present study may assist with preoperative patient counseling and prognosis.

PURPOSE: To investigate the performance of a machine learning model based on a reduced dimensionality parameter space derived from complete Pentacam parameters to identify subclinical keratoconus (KC). METHODS: All 1692 available parameters were obtained from the Pentacam imaging machine on 145 subclinical KC and 122 control eyes. We applied a principal component analysis (PCA) to the complete Pentacam dataset to reduce its parameter dimensionality. Subsequently, we investigated machine learning performance of the random forest algorithm with increasing numbers of components to identify their optimal number for detecting subclinical KC from control eyes. RESULTS: The dimensionality of the complete set of 1692 Pentacam parameters was reduced to 267 principal components using PCA. Subsequent selection of 15 of these principal components explained over 85% of the variance of the original Pentacam-derived parameters and input to train a random forest machine learning model to achieve the best accuracy of 98% in detecting subclinical KC eyes. The model established also reached a high sensitivity of 97% in identification of subclinical KC and a specificity of 98% in recognizing control eyes. CONCLUSIONS: A random forest-based model trained using a modest number of components derived from a reduced dimensionality representation of complete Pentacam system parameters allowed for high accuracy of subclinical KC identification.

To introduce an assessment tool (rubric) for evaluating ophthalmology residents' competency in pterygium surgery.A panel of experienced international surgeons collaborated and developed the rubric. After describing various stages of the procedure, the Dreyfus scale of skill acquisition was used for scoring each stage. After finalizing the rubric, two surgeons independently evaluated 20 masked pterygium surgery videos of 10 residents and scored the videos according to the rubric. The agreement between the scores of them was examined with the intra-class correlation coefficient test.This rubric divides pterygium surgery into 13 different stages and covers the two most common techniques of pterygium surgery; conjunctival autograft and amniotic membrane transplant. The rubric showed face and content validity. Overall, an intraclass correlation coefficient of 0.90 (95% confidence interval 0.76-0.96, P 0.001) was achieved between the two surgeons. The residents scored significantly higher on surgeries performed later in their rotation compared to the earlier surgeries (4.32 ± 0.35 vs 3.96 ± 0.31, P = 0.006). Certain stages of pterygium surgery were more strongly correlated with the residents' past pterygium surgical experience.This study introduces an international rubric for assessing competency in pterygium surgery. In addition to face and content validity, this rubric shows high inter-rater reliability. This may be a useful tool for teaching and measuring competency in pterygium surgery.

Purpose: Few studies have explored the association of genetic variants in microRNA genes and binding sites with diabetic retinopathy (DR) in type 1 diabetes. We conducted a genome-wide scan for single nucleotide polymorphisms (SNPs) in these genes by using data from a genome-wide association study (GWAS). Methods: All known SNPs were imputed from our GWAS data (n = 325) of DR cases and diabetic controls (no DR). Relevant SNPS were extracted using miRNASNP and PolymiRTS (version 2) databases. χ2 tests and logistic regression (adjusting for age, sex, duration of diabetes, HbA1c, and hypertension) were used to test the association between the imputed SNPs and DR phenotypes (any DR, nonproliferative DR [NPDR], proliferative DR [PDR], diabetic macular edema [DME], and sight-threatening DR defined as PDR, severe NPDR, or clinically significant macula edema [CSME]) compared with diabetic controls. Top-ranking SNPs were genotyped in a larger cohort (N = 560) to confirm their association with DR. Results: Three SNPs (rs10061133, rs1049835, rs9501255) were selected and genotyped in the final cohort. Rs10061133 in MIR449b was protective of sight-threatening DR (odds ratio [OR] = 0.32, P = 3.68 в 10-4) and PDR (OR = 0.30, P = 8.12 в 10-4), and the associations became more significant as the cohort increased in size. Conclusions: Rs10061133 in MIR449b is significantly associated with a decreased risk of PDR and sight-threatening DR in Caucasian patients with type 1 diabetes. This can guide future studies on genetic risk profiling and on developing microRNA-related therapies for sight-threatening DR.

Purpose: To evaluate the safety and efficacy of dexamethasone intravitreal implant (Ozurdex, DEX implant) 0.7 and 0.35 mg in the treatment of patients with diabetic macular edema (DME).Design: Two randomized, multicenter, masked, sham-controlled, phase III clinical trials with identical protocols were conducted. Data were pooled for analysis.Participants: Patients (n = 1048) with DME, best-corrected visual acuity (BCVA) of 20/50 to 20/200 Snellen equivalent, and central retinal thickness (CRT) of ≥300 μm by optical coherence tomography.Methods: Patients were randomized in a 1:1:1 ratio to study treatment with DEX implant 0.7 mg, DEX implant 0.35 mg, or sham procedure and followed for 3 years (or 39 months for patients treated at month 36) at ≤40 scheduled visits. Patients who met retreatment eligibility criteria could be retreated no more often than every 6 months.Main Outcome Measures: The predefined primary efficacy endpoint for the United States Food and Drug Administration was achievement of ≥15-letter improvement in BCVA from baseline at study end. Safety measures included adverse events and intraocular pressure (IOP).Results: Mean number of treatments received over 3 years was 4.1, 4.4, and 3.3 with DEX implant 0.7 mg, DEX implant 0.35 mg, and sham, respectively. The percentage of patients with ≥15-letter improvement in BCVA from baseline at study end was greater with DEX implant 0.7 mg (22.2%) and DEX implant 0.35 mg (18.4%) than sham (12.0%; P ≤ 0.018). Mean average reduction in CRT from baseline was greater with DEX implant 0.7 mg (−111.6 μm) and DEX implant 0.35 mg (−107.9 μm) than sham (−41.9 μm; P < 0.001). Rates of cataract-related adverse events in phakic eyes were 67.9%, 64.1%, and 20.4% in the DEX implant 0.7 mg, DEX implant 0.35 mg, and sham groups, respectively. Increases in IOP were usually controlled with medication or no therapy; only 2 patients (0.6%) in the DEX implant 0.7 mg group and 1 (0.3%) in the DEX implant 0.35 mg group required trabeculectomy.Conclusions: The DEX implant 0.7 mg and 0.35 mg met the primary efficacy endpoint for improvement in BCVA. The safety profile was acceptable and consistent with previous reports.

Background This study aimed to determine the nature and incidence of severe limbal stem cell deficiency in Australia and New Zealand. Design A one-year pilot surveillance study with a one-year follow-up period was conducted in association with the Australian and New Zealand Ophthalmic Surveillance Unit. Participants The study included patients reported by practising ophthalmologists on the Surveillance Unit's database. Methods Ophthalmologists were provided with a definition of severe limbal stem cell deficiency, contacted on a monthly basis by the Unit and asked to report newly diagnosed cases. Main Outcome Measures Severe LSCD was defined as at least 6 clock hours of whorl-like epitheliopathy, an opaque epithelium arising from the limbus, late fluorescein staining of the involved epithelium, and superficial corneal neovascularisation or conjunctivalisation. Results On average, 286 report cards were sent by the Surveillance Unit to practising ophthalmologists each month (total 3429 over 12 months) and the Unit received an average of 176 responses per month (total 2111; 62% response rate). During the 1-year study period from April 2013-March 2014, 14 positive cases were reported to the Unit. A range of underlying aetiologies were implicated, with contact lens over-wear and cicatrising conjunctivitis being the most common (n = 3). Conclusions This surveillance study is the first worldwide to document the incidence of limbal stem cell deficiency, however due to study design limitations, it is likely to have been under-reported. It provides novel data on the demographics, clinical conditions and management of patients with limbal stem cell deficiency as reported by treating ophthalmologists.

This study aimed to investigate whether the single-nucleotide polymorphism (SNP) rs2910164 residing within microRNA-146a (miR-146a) is associated with diabetic microvascular complications diabetic nephropathy (DN), proliferative diabetic retinopathy (PDR) or diabetic macular oedema (DME) in either Caucasian patients with type 1 (T1DM) or type 2 (T2DM) diabetes mellitus. Caucasian patients with T1DM (n = 733) or T2DM (n = 2215) were recruited from ophthalmology, renal and endocrine clinics in Australia and the UK. Patients with T2DM were required to have diabetes mellitus (DM) for at least 5 years and be on treatment with oral hypoglycaemic drugs or insulin. In total, 890 participants had DN (168 with T1DM and 722 with T2DM), 731 had PDR (251 with T1DM and 480 with T2DM) and 1026 had DME (170 with T1DM and 856 with T2DM). Participants were genotyped for SNP rs2910164 in miR-146a. Analyses investigating association were adjusted for relevant clinical covariates including age, sex, DM duration, HbA1c and hypertension. A significant association was found between the C allele of rs2910164 and DN in the T1DM group (OR 1.93; CI 1.23–3.03; P = 0.004), but no association found in the T2DM group (OR 1.05; CI 0.83–1.32; P = 0.691). In the subset of T2DM patients, the C allele was specifically associated with DME (OR 1.25; CI 1.03–1.53; P = 0.025). No association with DME was found in the T1DM group (OR 0.87; CI 0.54–1.42); P = 0.583), or with PDR for either type of DM. Rs2910164 is significantly associated with microvascular complications DN in patients with T1DM and DME in patients with T2DM.

AimsTo compare 24 months outcomes of eyes with retinal angiomatous proliferations (RAPs) treated with antivascular endothelial growth factor (anti-VEGF) with a group of controls diagnosed with other neovascular age-related macular degeneration (nAMD) subtypes in a real-world setting.MethodsTreatment-naïve nAMD eyes that commenced anti-VEGF between January 2006 and November 2015 were identified from a registry of nAMD treatment outcomes. Cases were defined as eyes diagnosed with RAP. Three controls per case were selected among nAMD eyes with non-RAP lesions and matched on baseline visual acuity (VA), year of treatment initiation, anti-VEGF agent first injected and follow-up. Baseline VA was compared with 12 and 24 months VA. Change in VA, number of injections received, proportion of visits with active nAMD and time to first inactivation were compared between RAPs and controls.Results157 RAPs and 469 controls were included. Baseline VA (mean (SD)) increased at 12 months (61.4 (15.5) vs 68.7 (14.7) letters, pConclusionsRAPs responded well to anti-VEGF, with a significant improvement in VA persisting at 24 months. RAPs had better visual outcomes than controls at 12 and 24 months, tended to inactivate earlier and were less active throughout 2 years follow-up.

Background Diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) are sight-threatening complications of diabetes mellitus and leading causes of adult-onset blindness worldwide. Genetic risk factors for diabetic retinopathy (DR) have been described previously, but have been difficult to replicate between studies, which have often used composite phenotypes and been conducted in different populations. This study aims to identify genetic risk factors for DME and PDR as separate complications in Australians of European descent with type 2 diabetes. Methods Caucasian Australians with type 2 diabetes were evaluated in a genome-wide association study (GWAS) to compare 270 DME cases and 176 PDR cases with 435 non-retinopathy controls. All participants were genotyped by SNP array and after data cleaning, cases were compared to controls using logistic regression adjusting for relevant covariates. Results The top ranked SNP for DME was rs1990145 (p = 4.10 × 10− 6, OR = 2.02 95%CI [1.50, 2.72]) on chromosome 2. The top-ranked SNP for PDR was rs918519 (p = 3.87 × 10− 6, OR = 0.35 95%CI [0.22, 0.54]) on chromosome 5. A trend towards association was also detected at two SNPs reported in the only other reported GWAS of DR in Caucasians; rs12267418 near MALRD1 (p = 0.008) in the DME cohort and rs16999051 in the diabetes gene PCSK2 (p = 0.007) in the PDR cohort. Conclusion This study has identified loci of interest for DME and PDR, two common ocular complications of diabetes. These findings require replication in other Caucasian cohorts with type 2 diabetes and larger cohorts will be required to identify genetic loci with statistical confidence. There is considerable overlap in the patient cohorts with each retinopathy subtype, complicating the search for genes that contribute to PDR and DME biology. Electronic supplementary material The online version of this article (10.1186/s12881-018-0587-8) contains supplementary material, which is available to authorized users.

AIMS: This study aimed to determine the incidence, clinical features and management of cicatrising conjunctivitis in Australia and New Zealand, also enabling comparison with data from the United Kingdom. METHODS: A prospective surveillance study was conducted over 17 months via the Australian and New Zealand Ophthalmic Surveillance Unit with a one-year follow-up period. Practicing ophthalmologists on the Surveillance Unit’s database were asked to report recently diagnosed cases of cicatrising conjunctivitis on a monthly basis. Initial and follow-up questionnaires were sent to ophthalmologists who had reported positive cases to obtain demographic and clinical data. The minimum incidence of cicatrising conjunctivitis was calculated based on cases reported during the study period and from population data. RESULTS: During the 17-month study period (December 2011–April 2013), 56 cases of cicatrising conjunctivitis were reported. Data was obtained for 35 cases (62%) with a mean age of 74 years (range, 28–94 years). The most common aetiologies were ocular mucus membrane pemphigoid (n = 18 cases, 51.4%), Stevens–Johnson Syndrome (n = 3, 8.6%) and graft versus host disease (n = 3, 8.6%). The minimum incidence of cicatrising conjunctivitis in Australia and New Zealand was 1.5 per million, comparable to incidence data from the United Kingdom. CONCLUSIONS: This study is the first to prospectively record the incidence of cicatrising conjunctivitis in Australia and New Zealand and the second worldwide. It provides novel data on demographics and management of cicatrising conjunctivitis, as reported by treating ophthalmologists.

Objective To examine microorganisms and their antibiotic susceptibility from corneal specimens for community-acquired microbial keratitis at the Royal Victorian Eye and Ear Hospital. Methods A retrospective review of microbiological results from January to April 2014 was undertaken. Patients' medical records were identified from the hospital's dispensing records of ofloxacin eye drops. Corresponding microbiology results from corneal specimens (species of isolated organisms and antibiotic susceptibilities) were recorded. Results There were 164 patients included in the study, of which 85 cultured positive, typical for corneal specimens. Of these, 75% were Gram-positive bacteria, 16% Gram-negative and 2% fungi. The commonest organisms were Staphylococcus sp. (46%) and Streptococcus sp. (10%). Of the 76 cases where fluoroquinolone susceptibility was tested, five (6.6%) demonstrated antibiotic resistance (minimal inhibitory concentration≥4.0 μg/mL), significantly higher than the 0% reported in 2000 ( P =0.002). All Staphylococcus isolates resistant to ciprofloxacin were resistant to cefazolin but susceptible to vancomycin. In ciprofloxacin-resistant isolates of streptococci, susceptibility to cefazolin and vancomycin was observed. Conclusions Most organisms identified on corneal specimens were Gram-positive. Susceptibility to fluoroquinolones was still high, although a trend for increasing ciprofloxacin resistance was noted. Further investigation is necessary to investigate if this reflects a wider antibiotic resistance prevalent within the community.

Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study.Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot.The top ranked variant was rs3805931 with p = 2.66 × 10(-7), but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10(-5)) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10(-8)). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina.Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.

Surface treatment to a biomaterial surface has been shown to modify and help cell growth. Our aim was to determine the best surface-modified system for the treatment of limbal stem cell deficiency (LSCD), which would facilitate expansion of autologous limbal epithelial cells, while maintaining cultivated epithelial cells in a less differentiated state. Commercially available contact lenses (CLs) were variously surface modified by plasma polymerization with ratios of acrylic acid to octadiene tested at 100% acrylic acid, 50:50% acrylic acid:octadiene, and 100% octadiene to produce high-, mid-, and no-acid. X-ray photoelectron spectroscopy was used to analyze the chemical composition of the plasma polymer deposited layer. Limbal explants cultured on high acid-modified CLs outgrew more cells. Immunofluorescence and RT2-PCR array results indicated that a higher acrylic acid content can also help maintain progenitor cells during ex vivo expansion of epithelial cells. This study provides the first evidence for the ability of high acid-modified CLs to preserve the stemness and to be used as substrates for the culture of limbal cells in the treatment of LSCD.

ARC and NHMRC funded authors may self-archive the author accepted version of their paper (authors manuscript) after a 12-month embargo period from publication in an open access institutional repository.

This study aimed to determine the nature and incidence of severe limbal stem cell deficiency (LSCD) in Australia and New Zealand.A 1-year pilot surveillance study with a 1-year follow-up period was conducted in association with the Australian and New Zealand Ophthalmic Surveillance Unit.The study included patients reported by practising ophthalmologists on the Surveillance Unit's database.Ophthalmologists were provided with a definition of severe limbal stem cell deficiency, contacted on a monthly basis by the Unit and asked to report newly diagnosed cases.Severe LSCD was defined as at least 6 clock hours of whorl-like epitheliopathy, an opaque epithelium arising from the limbus, late fluorescein staining of the involved epithelium and superficial corneal neovascularization or conjunctivalization.On average, 286 report cards were sent by the Surveillance Unit to practising ophthalmologists each month (total 3429 over 12 months) and the Unit received an average of 176 responses per month (total 2111; 62% response rate). During the 1-year study period from April 2013 to March 2014, 14 positive cases were reported to the Unit. A range of underlying aetiologies were implicated, with contact lens over-wear and cicatrizing conjunctivitis being the most common (n = 3).This surveillance study is the first worldwide to document the incidence of limbal stem cell deficiency; however, because of study design limitations, it is likely to have been under-reported. It provides novel data on the demographics, clinical conditions and management of patients with limbal stem cell deficiency as reported by treating ophthalmologists.

Background: Mannose-binding lectin plays a central effector role in the lectin pathway of complement activation. Frequently occurring MBL2 polymorphisms result in mannose-binding lectin deficiency, which increases susceptibility to infection. We characterized mannose-binding lectin levels and function in non-inflamed and inflamed human eyes, and evaluated its relationship to blood mannose-binding lectin levels and function. Design: Prospective, observational clinical study with controls and cases. Participants: Twenty-seven patients with paired blood and ocular samples (aqueous and/or vitreous) including 15 controls (non-inflamed) and 12 cases (inflamed). Methods: Blood and ocular samples were collected from controls (n = 15) with quiet eyes during elective cataract surgery and cases with inflamed eyes including proven/suspected endophthalmitis (n = 11) and herpetic retinal vasculitis (n = 1). Mannan-binding and C4 deposition enzyme-linked quantify mannose-binding lectin levels and function. Main Outcome Measures: Blood and ocular mannose-binding lectin levels and function. Results: Of 27 patients, 10 (37%) were mannose-binding lectin-deficient (defined as blood mannose-binding lectin levels

PURPOSE: To evaluate the effectiveness of a laser-induced chorioretinal venous anastomosis (L-CRA) as a treatment for nonischemic central retinal vein occlusion (CRVO). DESIGN: Prospective, randomized, controlled, multicenter clinical trial. PARTICIPANTS: A total of 113 consecutive patients with a nonischemic CRVO of >3 months' duration and visual acuity of < or =20/50. METHODS: Patients were randomized to L-CRA (58 patients) or conventional care (55 patients). They underwent standardized retinal photography, fluorescein angiography, and ophthalmic examinations, together with standardized assessments of best-corrected visual acuity, performed by masked visual acuity assessors using Early Treatment Diabetic Retinopathy Study protocols. Analysis was performed by intention-to-treat. MAIN OUTCOME MEASURES: The primary outcome measure was change in visual acuity at 18 months. Secondary outcomes were progression of retinal ischemia and rates of adverse events. RESULTS: A total of 53 control patients and 55 treatment patients completed the study. The 2 groups were comparable for age, age- and gender-adjusted mean visual acuity, and most other parameters. In the treated group of 55 patients, 42 (76.4%) developed an L-CRA. Over the 18-month follow-up period, treated eyes had an 8.3 letter mean improvement from baseline compared with control eyes (P = 0.03). Treated eyes that developed a functional L-CRA achieved an 11.7 letter mean improvement from baseline over the control group after 18 months (P = 0.004). Conversion to the ischemic CRVO category occurred in 20.8% of control eyes and in 9.6% of treated eyes overall (P = 0.33). Of the treated group who developed an L-CRA where the retinal ischemia was due to progression of the CRVO, 4.9% progressed to the ischemic category (P = 0.03). Neovascularization developed at the site of the L-CRA in 10 of 55 treated eyes (18.2%). Vitrectomy surgery was required by 5 of 55 treated eyes (9.1%) because of macular traction or nonresolving vitreous hemorrhage. CONCLUSIONS: Chorioretinal venous anastomosis was created in 76.4% of eyes with nonischemic CRVO in this study. Eyes that developed an anastomosis had a significant improvement (11.7 letters) in final visual acuity after 18 months, compared with eyes in the control group (P = 0.004). Complications were managed successfully with careful follow-up and early intervention.

Aim: To investigate, in a large cohort of 2494 individuals with diabetes mellitus, whether functional single nucleotide polymorphisms in the promoter region of tumour necrosis factor ( TNF) and lymphotoxin-alpha ( LTA) genes are associated with type of diabetes or presence of diabetic retinopathy. Methods: A total of 334 type 1 diabetes and 999 type 2 diabetes participants with sight-threatening diabetic retinopathy, and 260 type 1 diabetes and 901 type 2 diabetes participants with no diabetic retinopathy or minimal non-proliferative diabetic retinopathy, were genotyped for two single nucleotide polymorphisms (rs1800629 and rs361525). Results: The A allele of rs1800629 was associated with type 1 diabetes ( p Conclusion: An association between the A allele of rs1800629 and type of diabetes was found. No association was found between two promoter variants of TNF and LTA, and diabetic retinopathy in a large cohort of Caucasian patients with type 1 diabetes and type 2 diabetes.

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.