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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. more...

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 more...

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 more...

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. more...

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. more...

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. more...

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. more...

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. more...

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. more...

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. more...

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. more...

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. more...

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 more...

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. more...

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. more...

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. more...

Current stem cell protocols for ischemic heart disease are limited by the small numbers of cells that can be obtained by bone marrow aspirate. To increase myocardial delivery of bone marrow stem cells in patients with chronic ischemic heart disease (CIHD), we used granulocyte colony stimulating factor (G-CSF) for bone marrow mobilization of CD34+ cells, enabling intracoronary infusion of large numbers of CD34+ stem cells. Patients with CIHD (n = 5) demonstrated significantly reduced numbers of CD34+ cells mobilized by G-CSF in comparison to age-matched controls. Sustained reduction in anginal symptoms and improvement in quality of life scores was seen in all patients following infusion of cells. Moreover, mean collateral flow grade at 12-month follow-up angiography significantly improved, indicating sustained myocardial neovascularization. No proliferative retinopathy was induced and no in-stent restenosis seen. However, in two patients with documented increase in collateral flow, complications arose, one developing an acute coronary syndrome and the other a lentigo maligna. These results demonstrate the feasibility of G-CSF mobilization, leukapheresis and intracoronary transfer of CD34+ stem cells in patients with CIHD, but longer-term studies are required to ensure that this protocol is safe and effective. more...

Aim: To evaluate the efficacy, safety, and therapeutic effect of topical ciclosporin A 0.05% as a steroid sparing agent in steroid dependent allergic conjunctivitis. Methods: Prospective, randomised, double masked, placebo controlled trial comparing signs, symptoms, and the ability to reduce or stop concurrent steroid in steroid dependent atopic keratoconjunctivitis and vernal keratoconjunctivitis using 0.05% topical ciclosporin A compared to placebo. Steroid drop usage per week (drug score), symptoms, and clinical signs scores were the main outcome measures. Results: The study included an enrolment of 40 patients, 18 with atopic keratoconjunctivitis and 22 with vernal keratoconjunctivitis. There was no statistical significant difference in drug score, symptoms, or clinical signs scores between the placebo and ciclosporin group at the end of the treatment period. No adverse reactions to any of the study formulations were encountered. Conclusions: Topical ciclosporin A 0.05% was not shown to be of any benefit over placebo as a steroid sparing agent in steroid dependent allergic eye disease. more...

BACKGROUND To evaluate the efficacy of amniotic membrane transplantation in primary pterygium surgery. METHODS Patients presenting to the outpatient clinic of the Royal Victorian Eye and Ear Hospital with primary pterygium requiring surgical management were included in this study. The pterygia were excised to bare sclera and the conjunctival defects were closed with amniotic membrane grafts. The primary outcome was pterygium recurrence. RESULTS Twenty-eight pterygia of 26 patients were included. Twenty-three patients (88%, 25 eyes) completed 12 months follow up. By 12 months postoperatively 16 of these eyes (64%) had developed corneal recurrence and a further two had developed a limbal recurrence (9%). Five required repeat surgery during the 12 month follow-up period. No association was found between pterygium recurrence and pterygium size (P = 0.33), amniotic membrane graft dimension (P = 0.12), patient age (P = 0.53) or patient sex (P = 0.63). CONCLUSION Amniotic membrane grafting for primary pterygium was associated with an unacceptably high recurrence rate in this population. more...

A lthough the treatment of microbial keratitis has changed with the introduction of new antimicrobials, the management principles still remain the same. In general, suspected microbial keratitis is treated with empirical therapy of intensive topical broad spectrum antimicrobials. This is because delaying treatment until the diagnosis is confirmed may worsen the visual outcome and allow further complications. Whether there is a need for microbiological investigation for all patients is contentious, as is empirical primary treatment with fluoroquinolone monotherapy. Microbial keratitis is rare in the absence of predisposing risk factors. In the past trauma and ocular surface compromise (for example, bullous keratopathy, exposure, etc) were the major risks. However, with the introduction of soft contact lenses and their widespread use since the 1980s, the demographic profile of those presenting with suspected microbial keratitis has changed. Figure 1 shows the demographic change in the age groups of those presenting with suspected microbial keratitis from 1985 to 1995 at Moorfields Eye Hospital in London, United Kingdom. Figure 1 (A) Corneal scrape results by age group, Moorfields Eye Hospital, 1985. (B) Corneal scrape results by age group, Moorfields Eye Hospital, 1995. The change in the presentation of suspected microbial keratitis over time was also reflected in the types of micro-organisms cultured as shown in Table 1. View this table: Table 1 Variation in the organisms cultured from corneal scrapes at Moorfields Eye Hospital from 1985 to 1995 Not only are there temporal changes in the pattern of presentation of microbial keratitis, there are also geographic differences in the pattern of presentation. Table 2 shows the different patterns of infection from reports of keratitis from various locations around the world. View this table: Table 2 Regional variation in the organisms cultured from corneal scrapes So it is evident that the empirical choice of antibiotics in the primary treatment of suspected microbial keratitis requires local contemporaneous data regarding … more...

Background In age-related macular degeneration (AMD) the complement system is thought to be activated by chronic oxidative damage with genetic variants identified in the alternative pathway as susceptibility factors. However, the involvement of the lectin pathway of complement, a key mediator of oxidative damage, is controversial. This study investigated whether mannose-binding lectin (MBL) levels and genetic variants in lectin pathway proteins, are associated with the predisposition to and severity of AMD. Methods MBL levels and single nucleotide polymorphisms (SNPs) in the MBL2 and the ficolin-2 (FCN2) gene were determined in 109 patients with AMD and 109 age- and sex-matched controls. Results MBL expression levels were equally distributed in both cases (early and late AMD) and controls (p>0.05). However, there was a trend towards higher median MBL levels in cases with late AMD compared to cases with early AMD (1.0 vs. 0.4 μg/ml, p = 0.09) and MBL deficiency (0.05 for all analyses) as were MBL2 genotypes. Similarly, there was no significant difference in allele frequencies in any SNPs in either the MBL2 or FCN2 gene in cases with early vs. late AMD. Conclusions SNPs of lectin pathway proteins investigated in this study were not associated with AMD or AMD severity. However, MBL levels deserve further study in a larger cohort of early vs. late AMD patients to elucidate any real effect on AMD severity. more...

Keratoconus is typically diagnosed through changes at the anterior ocular surface. However, we wished to assess if macular parameter changes might also occur in these patients. We assessed posterior changes through the use of optical coherence tomography and compared to a nonkeratoconus patient group. All subjects underwent clinical examination including macular thickness measurements. The generalized estimation equation model was used to estimate the means and compare the differences in various measurements between keratoconus and nonkeratoconus patients. A total of 129 keratoconus eyes of 67 cases and 174 nonkeratoconus eyes of 87 controls were analysed. Keratoconus individuals presented with a significantly greater mean retinal thickness in the central fovea, inner, and outer macula compared to the nonkeratoconus group (p<0.05). In addition, individuals presenting with the early signs of keratoconus had significantly greater inner and outer macular volume compared to the nonkeratoconus group (p<0.05). This study indicates the retina appears to thicken at the fovea and macula and had increased macular volume in keratoconus individuals compared to nonkeratoconus individuals. Thus we posit that structural retinal changes exist in keratoconus eyes that are additional to those typically seen in the anterior segment. more...

Aim: To retrospectively study 26 patients with squamous cell carcinoma (SCC) of the ocular surface to determine pathological and clinical characteristics of tumour associated with outcome. Methods: Patients with conjunctival SCC from St Vincent9s Hospital and the private ophthalmology practices of the authors were reviewed. Results: Patents were usually male (77%), elderly (69% > 60 years of age), with most lesions (81%) occurring at the limbus. Seven patients (27%) suffered recurrent ocular surface squamous neoplasia (OSSN) within 4–15 months and two of these patients (8%) died of metastatic disease. Intraocular invasion was noted in three patients (11%), while corneal and/or scleral invasion was found in eight (30%). Orbital invasion was noted in four patients (15%). Six required orbital exenteration. Preoperative impression cytology of five patients with minimally invasive disease showed OSSN in four (80%). In situ carcinoma could not be differentiated from minimally invasive disease using impression cytology. Preoperative diagnosis of SCC was made in 35% of cases. Clinical accuracy was higher for larger lesions (>10 mm) and those with hyperkeratosis. Conclusions: Conjunctival SCC occurs in sun damaged ocular surface, usually at the limbus in elderly men. Recurrence of OSSN is common with significantly increased risk for older patients, lesions of large diameter, high proliferation index (Ki-67 score), and positive surgical margins. Orbital exenteration may be required for control of local disease and death from metastatic disease occurs in a small percentage of patients. more...

Purpose: To evaluate the safety and efficacy of botulinum toxin type A (BOTOX, Allergan) when used to produce a protective ptosis in patients where a surgical tarsorrhaphy would otherwise be required. Methods: A total of 21 patients entered into the study. Doses of 2.5 and 5.0 units of BOTOX were injected into the levator palpebrae superioris muscle through the eyelid. The patients were followed daily where practical until a ptosis developed and then monitored 1–2 weekly until the ptosis was resolved. Injections were repeated, if necessary, until the underlying condition had healed. Results: Ptosis took an average ± SE of 4.0 ± 0.5 days to develop (range 2–8 days). Duration of ptosis was an average ± SE of 46.0 ± 12.1 days (range 1–206 days). The effective dosage was 5 units of BOTOX in 0.1 mL. In 16 patients, the ptosis produced by BOTOX was sufficient to allow the underlying disease to heal and a surgical tarsorrhaphy was avoided. One patient required a surgical tarsorrhaphy and three patients required other surgical intervention to correct the underlying condition. One patient was lost to follow up. Diplopia was seen in five patients but resolved in all cases. Conclusions: BOTOX was a suitable alternative to a surgical tarsorrhaphy. more...

OBJECTIVE: To review the spectrum of patients with alkali burns admitted over an 11-year period and to assess the clinical outcomes after the introduction of a standard alkali burn treatment protocol. DESIGN: Retrospective nonrandomized comparative study. PATIENTS AND INTERVENTIONS: A total of 121 patient records with alkali burns (n = 177 eyes) admitted to a tertiary hospital between 1987 and 1998 were reviewed. Eyes treated with a standard alkali burn treatment protocol, which included intensive topical steroids, ascorbate, citrate, and antibiotics, were compared with eyes treated by conservative management with antibiotics, and a short course of steroids. MAIN OUTCOME MEASURES: Time to corneal reepithelialization, final best-corrected visual acuity, and time to visual recovery, length of hospital stay, and complications were analyzed. RESULTS: The standard protocol tended to delay corneal reepithelialization by one day (P: = not significant) in eyes with grade 1 burns (n = 76) and by 2 days (P: = 0.04) in grade 2 burns (n = 52), with no difference in final visual outcome. There were 37 eyes with grade 3 burns. Those treated with the standard protocol showed a trend toward more rapid corneal reepithelialization. Twenty-seven of 29 (93%) eyes with grade 3 injuries achieved a final best-corrected visual acuity of 20/40 or better compared with 3 of 6 (50%) eyes not treated according to the standard protocol (P: = 0.02). Eyes with grade 4 burns (n = 12), whether treated with the standard protocol or not, required 10 to 12 weeks for corneal reepithelialization. There was no statistically significant difference in final visual acuity. CONCLUSIONS: On the basis of our findings, a number of recommendations can be made for the management of alkali injuries. Patients with a grade 1 or 2 injury do not require routine admission and do not benefit from the use of intensive treatment with ascorbate and citrate. A trend toward more rapid healing and a better final visual outcome were apparent in grade 3 burns, but our standard protocol made no difference in grade 4 burns. more...

Thirteen human subjects scheduled for elective anterior segment eye surgery received hourly 2% voriconazole eye drops 4 hours presurgery. No side effects were reported. Significantly, the voriconazole concentration in the aqueous humor of the eye was similar to that reported for the 1% voriconazole solution, suggestive of concentration-independent absorption. more...

Aim: To analyse the clinical presentation, identify predisposing risk factors and evaluate the outcome of treatment of Moraxella keratitis. Methods: A retrospective analysis was carried out of culture-proved cases of Moraxella keratitis from hospital records during a 10-year period (from December 1995 to November 2005) at the Corneal Unit of the Royal Victorian Eye and Ear Hospital, Melbourne, Australia. Results: 95 episodes of Moraxella keratitis were identified in 92 patients. 3 (3.2%) patients had recurrent keratitis. The mean age of the patients was 70 (range 17–93) years. Multiple predisposing factors were identified in 23 (24%) eyes, including corneal graft (n = 15), previous herpes keratitis (n = 15) and eye lid diseases (n = 15). Adjunctive procedures were carried out in 42 eyes. These included botulinum toxin injection (n = 17), tarsorraphy (n = 12), penetrating keratoplasty (n = 8), enucleation (n = 3), tissue adhesive and bandage contact lens (n = 4), and conjunctival flap (n = 5). Polymicrobial infection was present in 17 eyes. Final visual acuity was counting finger or less in 25 (26%) eyes. Conclusions: Local ocular predisposing factors play a major role in Moraxella keratitis. This infection has a poor visual outcome attributable to both the nature of the infection and the predisposing factors. more...

PURPOSE: We assessed the impact of keratoconus disease indicators in the better eye and worse eye on quality of life (QoL) using the Vision and Quality of Life Index (VisQoL) multi-attribute utility instrument (MAUI). METHODS: ?tlsb -.01w?>Patients with keratoconus completed the six-item VisQoL utility measure. Visual acuity was assessed using a logMAR chart, and corneal thickness and the keratometric values were measured by using Scheimpflug imaging (Pentacam). Four indicators of keratoconus disease status were considered in this study, namely best corrected visual acuity (BCVA), average front corneal curvature (Front Km), thinnest corneal location (TCL), and spherical equivalent refractive error (SE). As keratoconus is an asymmetric condition, we considered the disease parameters separately for the better eye and the worse eye. The association between the four keratoconus indicators and VisQoL utilities was assessed using multivariate linear regression. RESULTS: A total of 170 patients with keratoconus completed the VisQoL. Patients' median age was 33 (IQR = 18) years (range, 14-75 years) and 58% (n = 99) were males. The median VisQoL utility value was 0.60 (IQR, 0.46; range, 0.02-0.99). The VisQoL utilities reduced with increasing age (ρ = -0.18, P = 0.02) and were higher for males (median = 0.65, IQR = 0.49) than females (median = 0.51, IQR = 0.40). In univariate analyses, BCVA in the better and worse eye, and Front Km and TCL in the worse eye were associated with lower VisQol utilities. However, after adjusting for relevant covariates, only BCVA in the better eye remained associated significantly with reduced VisQoL utilities (β = -0.20, P = 0.018). CONCLUSIONS: Using a vision-specific MAUI, our study demonstrated substantial disutility relating to keratoconus. Worse vision in the better eye (but not the worse eye) was associated independently with a reduction in VisQoL utilities, suggesting that considering VisQoL utilities based on vision in the better eye is an important estimate of the impact of keratoconus from the patients' perspective. Treatment and rehabilitation interventions to retard the progression of vision impairment in the better eye resulting from keratoconus would be most efficacious at an early stage to improve QoL outcomes for patients with this disease. more...

PURPOSE: A previous study has indicated suggestive association of the hepatocyte growth factor (HGF) gene with Keratoconus. We wished to assess this association in an independent Caucasian cohort as well as assess its association with corneal curvature. PARTICIPANTS: Keratoconus patients were recruited from private and public clinics in Melbourne, Australia. Non-keratoconic individuals were identified from the Genes in Myopia (GEM) study from Australia. A total of 830 individuals were used for the analysis including 157 keratoconic and 673 non keratoconic subjects. METHODS: Tag single nucleotide polymorphisms (tSNPs) were chosen to encompass the hepatocyte growth factor gene as well as 2 kb upstream of the start codon through to 2 kb downstream of the stop codon. Logistic and linear regression including age and gender as covariates were applied in statistical analysis with subsequent Bonferroni correction. RESULTS: Ten tSNPs were genotyped. Following statistical analysis and multiple testing correction, a statistically significant association was found for the tSNP rs2286194 {p = 1.1×10-(3) Odds Ratio 0.52, 95% CI--0.35, 0.77} for keratoconus. No association was found between the 10 tSNPs and corneal curvature. CONCLUSIONS: These findings provide additional evidence of significant association of the HGF gene with Keratoconus. This association does not appear to act through the corneal curvature route. more...

PURPOSE: A recent genome-wide association study (GWAS) identified six loci associated with central corneal thickness that also conferred associated risk of keratoconus (KC). We aimed to assess whether genetic associations existed for these loci with KC or corneal curvature in an independent cohort of European ancestry. METHODS: In total, 157 patients with KC were recruited from public and private clinics in Melbourne, Australia, and 673 individuals without KC were identified through the Genes in Myopia study from Australia. The following six single-nucleotide polymorphisms (SNPs) that showed a statistically significant association with KC in a recent GWAS study were selected for genotyping in our cohort: rs4894535 (FNDC3B), rs1324183 (MPDZ-NF1B), rs1536482 (RXRA-COL5A1), rs7044529 (COL5A), rs2721051 (FOXO1), and rs9938149 (BANP-ZNF469). The SNPs were assessed for their association with KC or corneal curvature using logistic or linear regression methods, with age and sex included as covariates. Bonferroni corrections were applied to account for multiple testing. RESULTS: Genotyping data were available for five of the SNPs. Statistically significant associations with KC were found for the SNPs rs1324183 (P = 0.001; odds ratio [OR], 1.68) and rs9938149 (P = 0.010; OR, 1.47). Meta-analysis of previous studies yielded genome-wide significant evidence of an association for rs1324183, firmly establishing it as a KC risk variant. None of the SNPs were significantly associated with corneal curvature. CONCLUSIONS: The SNPs rs1324183 in the MPDZ-NF1B gene and rs9938149 (between BANP and ZNF4659) were associated with KC in this independent cohort, but their association was via a non-corneal curvature route. more...

Empirical antibacterial therapy in keratitis is based on the likely pathogen, the available drugs, and the severity of the condition.1 Ongoing treatment is modified by clinical response and the result of initial microbial investigations.2 There is a large degree of variation in organism type and their resistance patterns from centre to centre, and so local contemporaneous data are essential to make a rational choice of initial antibiotic therapy. Reference centres specialising in corneal disease with good microbiological backup have a key role in analysing local trends and disseminating their results. Ongoing audit is also required, as patterns of resistance are invariably changing.3 Overall, there are some common pathogens that cause acute bacterial keratitis. Streptococcal species, staphylococcal species, pseudomonas and enterobacteriaceae make up the four most common classes of infective agents and any empirical therapy has to cover all these groups. There have been some concerns about the lack of in vitro efficacy by fluoroquinolone in the streptococcal species.4,5 In practical terms, this has not proved to be a common problem to date in the United Kingdom and Australia.6 In vitro resistance is based on the MIC90 and assumes drug levels found following intravenous infusion. However, topical administration can produce far higher tissue levels in the cornea than those obtained by intravenous administration and can be effective in local control of streptococcal keratitis. That being said, there will be occasions where the MIC90 will be at such a level that topical administration cannot control the disease and we have certainly had clinical experience of resistant streptococci. Newer methods to assess in vitro sensitivity other than the Kirby-Bauer test that can provide a more clinically relevant definition of resistance need to be introduced. Penicillin or cephalosporins have been … more...

Purpose To evaluate the factors influencing the successful creation of a laser-induced chorioretinal venous anastomosis (L-CRA) and those involved in the development of complications. Design Interventional cohort study. Participants Fifty-five patients with a nonischemic central retinal vein occlusion (CRVO) who were randomized to receive an L-CRA from the total of 108 who completed the follow-up period of the Central Vein Bypass Study. Methods Patients who were randomized to L-CRA were followed up for an 18-month period. They were stratified in 2 sets of 2 cohorts: those who did or did not demonstrate an L-CRA and those who did or did not demonstrate neovascular complications at the site of the L-CRA. Subgroup analysis was performed to determine what factors influenced the creation of an L-CRA and the development of complications at each individual laser site. Main Outcome Measures Identification of systemic and local ocular factors associated with increased success rates of L-CRA creation and those involved with an increased risk of neovascular complications. Results Younger age ( P = 0.03), better baseline visual acuity ( P = 0.04), and the absence of hypertension ( P = 0.001) were systemic features associated with an increased chance of demonstrating a successful L-CRA at each site, whereas sex and duration of the CRVO were not. The position of the L-CRA site did not influence the outcome; however, evidence of rupture of the vein wall at the time of the attempt was associated with a higher chance of success ( P = 0.008). Increased risk of neovascularization, which occurred at 12 sites in 10 eyes, was associated with higher central venous pressure before treatment ( P = 0.03), prolonged fluorescein transit time ( P = 0.0001), and the presence of some capillary nonperfusion ( P = 0.01). Conclusions Younger age, better baseline visual acuity, and the absence of hypertension were associated with an improved success rate, as was evidence of rupture of the vein wall. High baseline central venous pressure, prolonged fluorescein transit time, and the presence of any retinal ischemia were associated with a higher incidence of neovascular complications. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references. more...

To compare the incidence of corneal perforation in eyes treated with topical fluoroquinolone or fortified antibiotics for microbial keratitis.A retrospective medical record review of patients hospitalized for bacterial keratitis from January 1991 through November 1999.Two hundred seventy-seven cases of bacterial keratitis were identified. The incidence of corneal perforations was significantly higher in fluoroquinolone-treated eyes (18 out of 142, 12.7%) compared with eyes treated with fortified antibiotics (1 out of 135, 0.7%) (chi-square = 13.6, degrees of freedom (df) = 2, P.001). Within the fluoroquinolone-treated group, all corneal perforations occurred in those eyes treated with ofloxacin (18 out of 125, 14.4%). Corneal perforations that occurred in the ofloxacin-treated eyes were not associated with any particular microbial isolate.Our data suggest an increased risk of corneal perforation after fluoroquinolone treatment for bacterial keratitis compared with treatment with fortified antibiotics. Further studies are warranted to verify this association and establish possible mechanisms by which topical fluoroquinolones may alter corneal collagen or keratocyte function. more...

A 29 year old woman, who was an intermittent contact lens wearer, is referred from her local ophthalmologist with a diagnosis of microbial keratitis. There is a large central corneal ulcer with stromal white cell recruitment and low grade anterior chamber (AC) activity. The patient has no other eye problems and is in good health. Would you perform a corneal scraping? Which antibiotics would you use to begin empirical treatment for her microbial keratitis? more...

AIM—To evaluate the accuracy of impression cytology employing a Biopore membrane device in the diagnosis of ocular surface squamous neoplasia (OSSN). METHODS—The histology of patients undergoing excision biopsy for the suspected diagnosis of OSSN over a 20 month period was compared with the reported cytology of impression cytology specimens obtained preoperatively using the Biopore membrane device. RESULTS—25 excision biopsies were performed for suspected OSSN. There was accurate correlation in 20 out of the 25 cases (80%). In three cases (12%), there was poor correlation in that only a few dysplastic cells and hyperkeratosis were noted on cytology, whereas histology showed keratinising dysplasia in two cases and a moderately differentiated keratinising squamous cell carcinoma in the third. There were two cases (8%) of non-correlation—one keratinising dysplasia on histology, but anucleate keratin, squamous metaplasia, and rare atypical cells on cytology, and another case with very mild focal dysplasia on histology but squamous metaplasia on cytology. Review of the cytology showed that dysplastic cells were either rare or absent from the cytology specimens in these two cases; it was felt that these represented sampling problems rather than true false negatives. There were no false positives on cytology. Final diagnosis on histology was squamous cell carcinoma in one; carcinoma in situ in two; keratinising dysplasia in 15, non-keratinising dysplasia in seven. CONCLUSION—Impression cytology employing the Biopore membrane accurately predicts the histological diagnosis of OSSN. The presence of hyperkeratosis, inflammatory cells with only a few dysplastic cells, may indicate high grade keratinising dysplasia or squamous cell carcinoma. The method is both rapid and easy to perform in routine clinical practice. These findings suggest that there may be a role for its use in the initial assessment and follow up of patients with suspected OSSN. more...

Aims—To demonstrate that oral cyclosporin is successful in the management of steroid refractory post-keratoplasty atopic sclerokeratitis (PKAS). Methods—Series of three patients. Results—The patients developed PKAS between 2 and 11 days after surgery. All cases failed to respond to oral prednisolone 60‐80 mg daily for 10‐30 days but resolved with the addition of systemic cyclosporin 5.0‐7.5 mg/kg/day. There have been no relapses following withdrawal of therapy after 3‐18 months. Conclusions—PKAS is an uncommon, but severe, complication of corneal graft surgery and often responds to oral prednisolone treatment. Oral cyclosporin results in rapid resolution of PKAS in steroid unresponsive cases. (Br J Ophthalmol 2001;85:91‐92) Penetrating keratoplasty may be required to treat keratoconus and corneal scarring associated with atopy related eye diseases. 1 more...

Background: Description of the clinical and microbiological spectrum of fungal keratitis at a tertiary eye care hospital in Melbourne, Australia. Methods: Retrospective review of all patients with keratitis with positive fungal cultures from corneal or associated samples presenting to the Royal Victorian Eye and Ear Hospital, Melbourne, Australia from July 1996 to May 2004. Demographic data, predisposing factors, features on presentation, management, outcomes and microbiological data were collected and analysed. Results: The study included 56 eyes of 56 patients. Thirtyfive patients were treated as ‘typical’ fungal keratitis and used for description and analysis, with a mean follow up of 18 months. Ocular trauma (37.1%), chronic steroid use (31.4%) and poor ocular surface (25.7%) were the major predisposing factors. Perforation was seen in 25.7% of patients, penetrating keratoplasty was required in 9 (25.7%) patients and evisceration was performed in 2 (5.7%) patients. Candida albicans (13 patients, 37.2%) was the most common fungal isolate accounting for more than one-third of all organisms followed by Aspergillus fumigatus (six patients, 17.1%) and Fusarium sp. (five patients, 14.3%). Conclusions: The present study describes the clinical patterns of fungal keratitis in Melbourne, Australia and contrasts them with reports from other areas of the world. A high incidence of C. albicans infection and the prior use of steroids in high proportion of the patients are highlighted in this study. more...

Objective To determine the therapeutic efficacy of adjuvant use of voriconazole, 1 %, eyedrops in the treatment of refractory fungal keratitis. Methods A prospective open-label trial was conducted to determine voriconazole levels obtained in human aqueous humor after administration of a 1% solution, preserved with 0.01% benzalkonium chloride, every 6 hours for 3 days, or hourly for 4 doses. Ten participants were selected among patients scheduled to undergo elective anterior segment surgery, and samples were tested using validated high-performance liquid chromatography. Results The mean (SD) voriconazole concentrations after hourly dosing (n = 5) was 1.90 (1.12) μg/mL and after a single dosing every 6 hours (n = 5) was 0.94 (1.21) μg/mL, respectively. The mean (SD) sampling times after the last administration of eyedrops were 1.1 (0.5) hours after hourly dosing and 2.1 (0.6) hours after a single dosing every 6 hours. Conclusions Voriconazole, 1%, eyedrops are well tolerated and penetrate into human aqueous humor when administered at hourly or 6-hourly intervals. They are effective in treatingCandidaandAspergilluskeratitis, are substantially more affordable than oral therapy, and have less potential to cause systemic adverse effects. more...