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Purpose: Meibomian gland dysfunction (MGD) is a chronic progressive disease with downstream effects on ocular signs and symptoms. AZR-MD-001 is a selenium sulfide ophthalmic ointment that was investigated as a potential treatment option for patients with MGD., Methods: A Phase 2, multi-center, double-masked, parallel group study was conducted across 29 sites, with 245 patients randomized 1:1:1 to AZR-MD-001 0.5%, AZR-MD-001 1.0% or vehicle applied to the lower eyelid, twice weekly. Patients were eligible for the trial if they presented with signs and symptoms of MGD. Co-primary efficacy endpoints were the changes from baseline in number of open glands (Meibomian Glands Yielding Liquid Secretion [MGYLS] score) and patient-reported ocular surface symptoms (Ocular Surface Disease Index [OSDI] total score) at Month 3. Efficacy outcomes were captured at Day 14, Month 1.5 and Month 3. Safety and tolerability were assessed for treatment-emergent adverse events (TEAEs)., Results: AZR-MD-001 0.5% (n = 82 patients) treatment resulted in significant improvements in MGYLS score, with patients experiencing an average increase from baseline of 4.2 and 2.4 open glands secreting meibum for the drug and vehicle, respectively (p < 0.001) and from baseline a mean OSDI total score improvement of 7.3 and 3.8 for the drug and vehicle, respectively (p < 0.05). Most TEAEs were mild and transient, with 3 serious adverse events (SAEs) reported with AZR-MD-001 (none related to study drug)., Conclusions: Co-primary endpoints were met for AZR-MD-001 0.5% at Month 3, with a statistically significant improvement in the signs and symptoms of MGD. AZR-MD-001 was safe and well tolerated., Trial Registration: ClinicalTrials.gov Identifier: NCT03652051, ANZCTR Registration Number: AZ201801., Competing Interests: Declaration of competing interest Stephanie Watson (ORCID ID: 0000-0001-6699-1765): Within the past 3 years, SW has received grant support, allocated to her research group, from Seqirus; has participated on an advisory board for Alcon Global; and has received honoraria for lectures or speakers bureaus from Novartis and Seqirus. SW also serves as a Chair of Australian Vision Research and is an inventor on US Patent US20200281924. Lyndon W. Jones (ORCID ID: 0000-0002-7409-7349): Within the past 3 years, LWJ has received research support or lectureship honoraria from the following companies, allocated to the Centre for Ocular Research and Education (CORE): Alcon, Azura Ophthalmics, Bausch Health, CooperVision, Essilor, Hoya, i-Med Pharma, J&J Vision, Menicon, Novartis, Ophtecs, Oté Pharma, Santen, SightGlass, SightSage, Topcon and Visioneering. LWJ is also a consultant and/or serves on an advisory board for Alcon, CooperVision, J&J Vision, Novartis and Ophtecs. Fiona Stapleton: Within the past 3 years, FS has received research support from the following companies: Alcon, Azura Ophthalmics, Exonate, Kedalion Therapeutics, Menicon, Novartis and Nthalmics. FS has also been a consultant for CooperVision and has participated on advisory boards for Alcon, Seqirus, and Novartis. FS is the immediate past-president of the International Society for Contact Lens Research and is a steering committee member and subcommittee chair of Tear Film and Ocular Surface Society, Lifestyle Epidemic Workshop. Mark Hinds: MH has received research funding and/or honoraria from Vyluma, Kiora Pharmaceuticals, SynergEyes, CORE Research Group (Eli Lilly and Company), Novo Nordisk, Alcon and the Queensland University of Technology (School of Optometry and Vision Science). He has provided expert testimony for Remedy Medicolegal, Avant Insurance and Murphey's Law. MH is also a consultant for and/or serves on an advisory board for Kiora Pharmaceuticals and the Dry Eye Society. Alison Ng (ORCID ID: 0000-0002-6277-8470): AN is an employee of the Centre for Ocular Research and Education (CORE). Within the past 3 years, her institution has received research funding and/or honoraria from the 17 companies and 7 funding agencies listed: Alcon, Azura Ophthalmics, Bausch + Lomb Corp, CooperVision, Essilor, Hoya, I-MED Pharma, Johnson & Johnson Vision, Menicon, Novartis, Ophtecs, Oté Pharma, Santen, SightGlass, SightSage, Topcon, Visioneering Tech Inc, NSERC, CIHR, Mitacs, Canadian Association of Optometrists, European Commission Horizon 2020, Canada Foundation for Innovation, Innovation and Technology Commission (Government of the Hong Kong Special Administrative Region of the People's Republic of China). Jacqueline Tan (ORCID ID: 0000-0003-4986-4945): Within the past 3 years, JT has received research funding (paid to institution) from Alcon, Azura Ophthalmics, Exonate, Kedalion Therapeutics, Novartis, nthalmic and Rodenstock; has received support for attending International Society for Contact Lens Research and Tear Film and Ocular Society; has participated on an advisory board for Azura Ophthalmics; and has received non-monetary support (e.g., equipment, materials, other services) from Melcare and OptiMed. Yair Alster: YA is an inventor on patents related to AZR-MD-001 and is an employee of and has stock and options in Azura Ophthalmics. Charles Bosworth: CB is an employee of Azura Ophthalmics. Omer Rafaeli: OR is an employee of Azura Ophthalmics. Venita DePuy: VD is a statistical consultant to Azura Ophthalmics., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

The ocular surface, comprised of the corneal and conjunctival epithelium, innervation system, immune components, and tear-film apparatus, plays a key role in ocular integrity as well as comfort and vision. Gene defects may result in congenital ocular or systemic disorders with prominent ocular surface involvement. Examples include epithelial corneal dystrophies, aniridia, ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome, xeroderma pigmentosum (XP), and hereditary sensory and autonomic neuropathy. In addition, genetic factors may interact with environmental risk factors in the development of several multifactorial ocular surface disorders (OSDs) such as autoimmune disorders, allergies, neoplasms, and dry eye disease. Advanced gene-based technologies have already been introduced in disease modelling and proof-of-concept gene therapies for monogenic OSDs. For instance, patient-derived induced pluripotent stem cells have been used for modelling aniridia-associated keratopathy (AAK), XP, and EEC syndrome. Moreover, CRISPR/Cas9 genome editing has been used for disease modelling and/or gene therapy for AAK and Meesmann's epithelial corneal dystrophy. A better understanding of the role of genetic factors in OSDs may be helpful in designing personalized disease models and treatment approaches. Gene-based approaches in monogenic OSDs and genetic predisposition to multifactorial OSDs such as immune-mediated disorders and neoplasms with known or possible genetic risk factors has been seldom reviewed. In this narrative review, we discuss the role of genetic factors in monogenic and multifactorial OSDs and potential opportunities for gene therapy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Posterior blepharitis and dry eye are common disorders with meibomian gland dysfunction (MGD), a principal driver of their pathophysiology. Meibomian gland dysfunction is increasingly prevalent in older populations with contributory hormonal imbalances. The abnormal meibum in MGD has been documented to have an excess of cholesterol with a resultant disruption of the lipid layer of the tear film. This leads to tear film instability due to the inadequate trapping of the aqueous portion of the tear film with resultant evaporative dry eye. Significant morbidity may follow MGD with ocular surface inflammation disrupting both social and work function. Rosacea is a common chronic inflammatory condition of the central face but can have ocular and systemic inflammatory associations. It is especially prevalent in North European populations and can have onset at any age, but commonly presents between thirty and fifty years of age. In ocular rosacea, MGD is a recognised manifestation as is dyslipidaemia. Ocular rosacea can predate cutaneous disease. As yet, there is no directly reported evidence of the efficacy of the early identification and treatment of ocular rosacea with associated dyslipidaemia and systemic inflammation. We posit that MGD in ocular rosacea sufferers may be a marker for dysregulated cholesterol synthesis and inflammation, and that statins maybe a potential therapy. This article introduces potential strategies to utilise ocular rosacea MGD as a possible marker for ophthalmologists, cardiologists, and primary healthcare physicians to treat rosacea-associated dyslipidaemia and systemic inflammation. This could aid in overall cardiovascular morbidity and mortality control for rosacea sufferers, potentially at an earlier age, while also addressing their tear film de-stabilisation through cholesterol lowering and inflammation reduction.

Purpose: The aim of this study was to evaluate the quality-of-life (QoL) status in keratoconus severity subgroups using the Keratoconus Outcomes Research Questionnaire (KORQ) and to determine the relationship between the QoL scores and the standard clinical variables., Methods: A cross-sectional study was conducted using prospective, web-based Save Sight Keratoconus Registry data. Rasch analysis was conducted on the KORQ data using the Andrich Rating Scale Model. Comparative analysis included Welch t test and 1-way ANOVA. Associations between visual acuity, corneal curvature, and minimum corneal thickness with KORQ scores were evaluated with Pearson correlation and multiple regression adjusted for age and sex., Results: The KORQ was completed by 542 patients with keratoconus (male, 67.7%; mean age, 31.6 years). Keratoconus severity, based on Kmax, was mild [<48 diopter (D)], moderate (48-55 D), and severe (>55 D) in 26.3%, 45.0%, and 28.7% of patients, respectively. Activity limitation (AL) and symptoms (SY) scales of the KORQ had robust psychometric properties including well-functioning response categories, unidimensionality, excellent measurement precision, and satisfactory fit statistics. In a group-wise analysis, the female patients had significantly lower AL and SY scores. Similarly, the severe keratoconus group had the worst AL and SY scores. Contact lens wearers had worse KORQ scores than the spectacles wearers. Overall, statistically significant but weak correlations between KORQ scores and visual acuity and corneal curvature (Kmax and K2) (Pearson r, 0.11-0.35) were observed. The correlations for SY were weaker than for AL scores., Conclusions: Female sex, contact lens wear, reduced visual acuity, and higher disease severity were associated with worse AL and SY scores in keratoconus. Although the correlations between clinical and QoL scores were statistically significant, the low magnitudes suggested a complex relationship between clinical parameters and patient-reported outcomes., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The objective of this study was to compare the effectiveness and safety of short versus standard riboflavin induction times in cross-linking (CXL) for keratoconus., Methods: A retrospective comparative study was conducted with data from the Save Sight Keratoconus Registry. Inclusion criteria were epithelium-off technique, standard UVA CXL protocol (3 mW/cm 2 for 30 minutes), riboflavin induction for 15 minutes (short) or 30 minutes (standard), and 1 year of follow-up data after CXL. Outcome measures included changes in best-corrected visual acuity (BCVA), keratometry in the steepest meridian (K2), maximum keratometry (Kmax), thinnest pachymetry (TCT), and adverse events. Analysis was conducted using mixed-effects regression models adjusted for age, sex, visual acuity, keratometry, pachymetry, practice, and eye laterality., Results: Two hundred eighty eyes (237 patients; mean, 27.3 ± 10.5 years old; 30% female) were included. The riboflavin induction time was short in 102 eyes (82 patients) and standard in 178 eyes (155 patients). The baseline characteristics (sex, mean age, BCVA, keratometry, and pachymetry [TCT]) were similar between the groups. At the 1-year follow-up visit, no statistically significant differences were observed in flattening in K2 and improvement in BCVA. Greater Kmax flattening [-1.5 diopters (D) vs. -0.5D, P = 0.031] and a greater proportion of >2% increase in TCT (23.5 vs. 11.3, P = 0.034) and haze (29 vs. 15, P = 0.005) were observed with short riboflavin induction., Conclusions: Short and standard riboflavin induction times achieved similar degrees of flattening in K2 and improvement in vision. Greater improvements in Kmax and TCT were seen with short riboflavin times; however, this group had higher rates of haze., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The rise of primary topical monotherapy with chemotherapeutic drugs and immunomodulatory agents represents an increasing recognition of the medical management of ocular surface squamous neoplasia (OSSN), which may replace surgery as the standard of care in the future. Currently, there is no consensus regarding the best way to manage OSSN with no existing guidelines to date. This paper seeks to evaluate evidence surrounding available treatment modalities and proposes an approach to management. The approach will guide ophthalmologists in selecting the most appropriate treatment regime based on patient and disease factors to minimize treatment related morbidity and improve OSSN control. Further work can be done to validate this algorithm and to develop formal guidelines to direct the management of OSSN.

Purpose: The objective of this study was to undertake a systematic review of the literature reporting on clinical registries in dry eye disease (DED)., Methods: Electronic searches were conducted using systematic review methodology to provide an overview of clinical registries in ophthalmology and to identify clinical registries reporting on dry eye parameters. Two reviewers independently assessed titles and abstracts, then full-texts for eligibility., Results: A total of 129 clinical registries in ophthalmology were identified. The most common conditions captured were blindness or low vision, followed by glaucoma and corneal transplantation. Most of the registries originated in Europe (n = 56), followed by North America (n = 28). Of the registries identified, 12 were multinational, 59 were national, and 17 were regional. The second search identified 27 eligible articles, from which 8 clinical registries reporting on dry eye parameters were identified. One registry included patients with a diagnosis of dry eye. The remaining 7 registries included patients from a nationwide administrative ophthalmic database (n = 1), Sjögren syndrome (n = 4), glaucoma (n = 1), or were monozygotic and dizygotic twins (n = 1), who were evaluated for DED. Five of the registries were actively collecting data., Conclusions: Most of the registries identified in this review evaluated aqueous deficient dry eye; however, the most common type of dry eye in the general population is evaporative. Few registries also collected recommended dry eye clinical assessment. A well-designed clinical registry for DED that engages international eye care clinicians has the potential to vastly contribute to addressing pivotal gaps in understanding this highly prevalent disease., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Keratoconus is a disorder that results in visual loss from increased corneal high-order aberrations and irregular astigmatism and reduces quality of life. The primary treatment for progressive keratoconus is crosslinking (CXL). Recently, it has been suggested that oxygen enhances the type II photodynamic reaction of CXL that is oxygen dependent. Our study investigated the effect of increased oxygen availability in epithelium-on CXL on visual acuity and corneal curvature., Methods: We searched PubMed, EMBASE, Medline, Web of Science, and Scopus databases on November 3, 2021. We included studies that reported increased oxygen availability during CXL in patients with keratoconus published within the last 10 years. A meta-analysis on the primary outcomes, maximum keratometry, and corrected distance visual acuity, was conducted., Results: The search yielded 108 publications which were screened and assessed for eligibility. Six studies were included in the systematic review and 5 studies were included in our meta-analysis of the outcomes of increased oxygen availability in accelerated CXL. The meta-analysis on data after 6 months of follow-up found a significant decrease in mean maximum keratometry of 1.2 diopter (95% confidence interval: 0.2-2.3; P =0.02) and an improvement in mean corrected distance visual acuity by 0.08 logMAR (95% confidence interval, 0.02-0.13; P =0.01). There were no serious adverse events reported., Conclusions: Increasing oxygen during epithelium-on CXL improved visual acuity and produced corneal flattening without any serious adverse events in patients with keratoconus. The demarcation line depth was significantly higher with oxygen compared to the control group. Further data are required with a control group and long-term follow-up across a range of CXL protocols for implementation into standard clinical practice., Competing Interests: The authors have no conflicts of interest., (Copyright © 2022 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Purpose: To conduct a systematic review and meta-analysis on the efficacy of thin and ultrathin Descemet stripping automated endothelial keratoplasty (T-DSAEK and UT-DSAEK, with graft thickness <130 and <100 µm, respectively), depending on graft thickness., Design: Systematic review and meta-analysis., Method: PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and ScienceDirect databases were searched until October 1, 2021. We computed random-effect meta-analysis on postoperative outcomes of T/UT-DSAEK, stratified by graft thickness (<80 μm, 80-100 μm, and 100-130 μm). The main postoperative outcome was visual acuity (logarithm of the minimum angle of resolution [logMAR]). Secondary outcomes were pachymetry (μm), endothelial cell count (cell/mm 2 ), spherical equivalent (diopter [D]), rebubbling rate (%), and rejection rate (%). Meta-regressions compared postoperative outcomes depending on graft thickness and search for putative confusion factors., Results: We included 47 articles for a total of 2141 eyes of 2040 patients. T/UT-DSAEK globally improved visual acuity (effect size = -0.38 logMAR [95% confidence interval {CI} -0.46 to -0.30 logMAR]), without difference depending on graft thickness. Overall, pachymetry improved (-60.6 µm [95% CI -101 to -19.7 µm]), endothelial cell count decreased (-1039 cells/mm 2 [95% CI -1209 to -868 cells/mm 2 ), spherical equivalent resulted in a hyperopic shift (0.74 D [95% CI -0.50 to 1.97 D), the graft rejection rate was 0.2% (95% CI -0.1% to 0.4%), and the rebubbling rate was 8.7% (95% CI 6.8%-10.5%). Grafts >100 μm induced a hyperopic shift. Metaregressions did not demonstrate differences between the 3 groups (<80 μm, 80-100 μm, or 100-130 μm) in any outcomes., Conclusion: All T/UT-DSAEK thickness groups provided similar visual acuity, pachymetry, endothelial cell count, rejection rate, and rebubbling rate regardless of graft thickness. A hyperopic shift was induced by grafts >100 μm., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Globally, infectious keratitis is the fifth leading cause of blindness. The main predisposing factors include contact lens wear, ocular injury and ocular surface disease. Staphylococcus species, Pseudomonas aeruginosa, Fusarium species, Candida species and Acanthamoeba species are the most common causal organisms. Culture of corneal scrapes is the preferred initial test to identify the culprit organism. Polymerase chain reaction (PCR) tests and in vivo confocal microscopy can complement the diagnosis. Empiric therapy is typically commenced with fluoroquinolones, or fortified antibiotics for bacterial keratitis; topical natamycin for fungal keratitis; and polyhexamethylene biguanide or chlorhexidine for acanthamoeba keratitis. Herpes simplex keratitis is mainly diagnosed clinically; however, PCR can also be used to confirm the initial diagnosis and in atypical cases. Antivirals and topical corticosteroids are indicated depending on the corneal layer infected. Vision impairment, blindness and even loss of the eye can occur with a delay in diagnosis and inappropriate antimicrobial therapy., (© 2022 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: The study aimed to test whether symptomatic dry eye in aromatase inhibitor (AI) patients is associated with the clinical features of evaporative dry eye., Methods: A cross-sectional, observational study of postmenopausal women treated with AI was conducted. Clinical information was gathered from their treating clinician. Ocular and treatment symptoms were assessed using validated questionnaires. Clinical assessments were performed to assess for dry eye. The primary outcome measure for this study was dry eye symptoms measured via questionnaire. The secondary outcome measures were clinical signs of dry eye and hormone levels., Results: A total of 25 women on AI were recruited. 64% of women reported symptoms of dry eye (ocular surface disease index ≥ 13). Higher tear osmolarity (323 vs 307 mOsm/L, p = 0.002) and increased meibomian gland dropout (4 vs 1, p = 0.002) were observed in patients with symptomatic dry eye when compared to asymptomatic patients. Multivariate logistic regression identified that longer duration of AI use and higher tear osmolarity increased the likelihood of a patient experiencing dry eye symptoms., Conclusion: Our study found increased tear osmolarity and meibomian gland drop out in women on AI with symptomatic dry eye. Longer duration of AI therapy and higher tear osmolarity may increase the risk of developing dry eye., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: Animal models are pivotal for elucidating pathophysiological mechanisms and evaluating novel therapies. This systematic review identified studies that developed or adapted animal models of limbal stem cell deficiency (LSCD), assessed their reporting quality, summarized their key characteristics, and established their clinical translational relevance to human disease., Methods: The protocol was prospectively registered (PROSPERO CRD42020203937). Searches were conducted in PubMed, Ovid EMBASE and Web of Science in August 2020. Two authors screened citations, extracted data, assessed the reporting quality of eligible studies using the ARRIVE guidelines, and judged the clinical translational relevance of each model using a custom matrix., Results: 105 studies were included. Rabbits were the most common animal species. Overall, 97% of studies recapitulated LSCD to a clinical etiology, however 62% did not provide sufficient methodological detail to enable independent reproduction of the model. Adverse events and/or exclusion of animals were infrequently (20%) reported. Approximately one-quarter of studies did not produce the intended severity of LSCD; 34% provided insufficient information to assess the fidelity of disease induction. Adjunctive diagnostic confirmation of LSCD induction was performed in 13% of studies., Conclusions: This is the first systematic review to assess the reporting quality and clinical translational relevance of animal models of LSCD. Models of LSCD have evolved over time, resulting in variable reporting of the characteristics of animals, experimental procedures and adverse events. In most studies, validation of LSCD was made using clinical tests; newer adjunctive techniques would enhance diagnostic validation. As most studies sought to evaluate novel therapies for LSCD, animal models should ideally recapitulate all features of the condition that develop in patients., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/objectives: To describe the predisposing factors, pathogens and outcomes in patients with clinical presumed concomitant microbial and herpes simplex keratitis (HSK) at Sydney Eye Hospital, Australia over a 5-year period., Subjects/methods: A retrospective case review was conducted. Patients with clinical presumed concomitant microbial and HSK from 2012 to 2016 were identified from pathology and hospital coding databases. Data were extracted from the medical records. VA was converted to the logarithm of the minimum angle of resolution (logMAR). 'Poor' outcome was defined as final VA worse than 6/60, or decrease in VA during treatment, or presence of complication, or needed surgical intervention., Results: 126 episodes in 121 patients were included; median age 70 years (range 18-96); 56% male. Predisposing factors included blepharitis 20/126 (16%) cases, and corneal transplantation 19 (15%). Forty-six (37%) cases had prior HSK. Coagulase-negative staphylococci 51/116 (44%), Staphylococcus aureus 11 (9%), and Pseudomonas aeruginosa 11 (9%) were the most common isolates. The median VA at initial visit was 1.7 logMAR (range 0.04-2.7) and at final visit, 0.98 logMAR (range 0-2.7) (P < 0.05). Complications occurred in 70 episodes: persistent epithelial defect in 38 (30%); intraocular pressure elevation in 15 (12%), and corneal perforation in 12 (10%). 'Poor' outcome was recorded in 46/75 (61%) episodes., Conclusions: Patients with clinical presumed concomitant microbial and HSK face significant ocular morbidity and poor visual outcome. In our setting, previous HSK, corneal and ocular surface disease, were common predisposing factors and Gram-positive bacteria were the most commonly associated organisms., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose of Review: The aim of this study was to summarize common eye changes that may occur during pregnancy, and how pregnancy may affect preexisting eye conditions such as glaucoma and diabetic retinopathy. Challenges and complexities surrounding the treatment of these eye conditions during pregnancy are also highlighted., Recent Findings: Refractive changes are common and may persist in the postpartum in patients with keratoconus. Although new medical and surgical glaucoma treatments are available, their safety in pregnancy is unknown. Limited use of topical and systemic glaucoma therapies is recommended, with a preference for selective laser trabeculoplasty as first line treatment in appropriate cases. The impact of pregnancy on diabetic retinopathy remains unclear. Although anti-vascular endothelial growth factor agents are first-line treatment for sight-threatening diabetic retinopathy, their effect on the developing foetus remains unknown and are therefore best avoided in the first and second trimesters. Noninfectious uveitis tends to become less active during pregnancy, allowing the potential tapering of systemic therapy and the use of local topical or injected corticosteroid treatment for active disease as required., Summary: Significant changes can occur to the eye during pregnancy, wherein the optimal treatment for many ocular conditions remains uncertain, highlighting the need for further research to develop clear recommendations that best balance the need to preserve the mother's sight, and the health of the developing foetus. The need for preconception planning, and collaborative multidisciplinary care between the obstetrician, physician, ophthalmologist and paediatrician is paramount., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this study was to report the clinical profile and microbiological of patients with microbial keratitis post accelerated corneal collagen cross-linking (CXL)., Methods: A retrospective case series of all patients diagnosed with microbial keratitis post-CXL who attended the Sydney Eye Hospital, Australia from January 1, 2012 to December 31, 2019 were included. Patients were identified from hospital coding and pathology data. Data were extracted from patients' medical records., Results: Eleven eyes from 10 patients with a mean age of 29 ± 11 years (range 16-48) were included. The median time of infection after CXL surgery was 4 days [interquartile range (IQR) 3-83]. Median initial and final Visual acuity at presentation were 1.3 logMAR (IQR 1-2.0) and 0.8 logMAR (IQR 0.6-1.2), respectively. The culture positivity rate was 92%, identifying 13 isolates, predominately made up of coagulase-negative Staphylococcus (n = 6, 50%) and Staphylococcus aureus (n = 3, 25%). The median epithelial healing time was 30 days (IQR 15-53)., Conclusions: Post-CXL microbial keratitis was predominately associated with gram-positive bacteria and in some cases delayed epithelialization. Microbial keratitis post-CXL may lead to moderate to poor patient outcomes., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Competing Interests: The authors have no conflicts of interest to declare.

Purpose: The aim of this study was to report topical steroid usage in bacterial keratitis and analyze the effects of steroids on patients' outcomes to the main causative organisms., Design: A retrospective case-series., Methods: This study included all patients with corneal scrape positive bacterial keratitis from January 2012 to December 2016 at the Sydney Eye Hospital, Sydney, Australia. Cases were identified from pathology results and hospital coding, and data collected from medical records., Results: A total of 313 eyes from 308 patients with a mean age of 51 years [interquartile range (IQR) 36-72] were included. Of these patients, 192 (61%) were treated with topical steroids. High-dose steroids were prescribed in 22 (11%) cases, regular-dose in 88 (46%), and low-dose in 82 (43%). The median time until the implementation of steroid use was 4 days (IQR 3-7). Patients prescribed with topical steroids had significantly longer healing times than the "no steroid" group (11 vs 6.5, P < 0.001). Patients with Pseudomonas aeruginosa keratitis and topical steroid use had worse clinical outcomes, with a higher proportion having longer healing times (P = 0.04) and corneal scarring (P = 0.02)., Conclusions: Adjuvant topical steroid therapy did not affect visual acuity, patient outcomes or the rate of adverse effects but may delay epithelial healing in bacterial keratitis in these patients. Topical steroids may have a differential effect depending on the specific causative organisms; however, a clinical trial is needed to assess this.

Purpose: To develop and measure the uptake of a local guideline for herpes simplex keratitis (HSK) and to standardize initial antiviral therapy in Australia., Methods: The Registered Nurses' Association of Ontario Toolkit: "Implementation of Best Practice Guidelines" was used to develop, implement, and evaluate the guideline at Sydney Eye Hospital. An implementation team was established to reach consensus on antiviral therapy guidelines through review of available evidence, identifying stakeholders, facilitators and barriers, creating strategies for implementation, and developing a sustainability plan. An audit of all adult HSK cases during a 6-month postguideline implementation period was conducted, and the results were compared with a preimplementation audit. A web-based survey was created to assess clinician awareness, usage, and level of knowledge of the guideline., Results: Clinicians, pharmacists, and administrative staff were identified as stakeholders. Changing clinician's behavior was the major barrier to implementation. Implementation strategies included printed and online materials and lectures to clinicians. A postimplementation audit included 85 patients, and 95 clinicians received a web-based survey. The dose of the prescribed antiviral medication was in alignment with the local guideline in 80% (51/64) of the patients compared with 73% (163/223) before implementation (P = 0.331). Stromal HSK with ulceration and keratouveitis were excluded because there were no recommendations before implementation. Over 70% of clinicians (30/41) were aware of the guideline and accessed them through educational resources., Conclusions: Guidelines for the management of HSK may improve standardization of initial antiviral therapy in HSK. In practice, most clinicians were aware of and adhered to the local guideline.

Purpose: The adoption of clinical registries has the potential to improve outcomes, while reducing the costs of health care. We sought to evaluate the changes in workflow that occurred with implementation of the Save Sight Keratoconus Registry (SSKR) in corneal clinics., Methods: A prospective time-motion study and a clinician survey were conducted. The timing of clinic consultations was recorded before and after implementation of the SSKR. The activities were assigned into 3 main categories: 1) direct patient care (eg, talking to, examining), 2) indirect patient care (record keeping), and 3) indirect patient care (reading)., Results: Overall, there was no change in average time spent per patient with or without the SSKR; 12.3 (5.3 SD) versus 12.1 (5.3 SD) minutes, respectively, P = 0.84. There was no change in time spent providing direct care with or without the SSKR; 5.4 (2.8 SD) versus 5.9 (2.8 SD) minutes, respectively, P = 0.51. Within direct patient care, there was no impact with or without the SSKR on the time spent examining (1.9 [1.0 SD] vs. 1.9 [1.4 SD] minutes, respectively, P = 0.58) or talking to patients (3.5 [2.3 SD] vs. 4.1 [2.3 SD] minutes, respectively, P = 0.21). Indirect care time was unchanged overall for record keeping (3.2 [2.2 SD] vs. 4.6 [2.9 SD], respectively, P = 0.16) and reading tasks (3.1 [1.8 SD] vs. 2.0 [1.3 SD], respectively, P = 0.09)., Conclusions: The SSKR was implemented into clinical practice without affecting the total consultation time, time spent directly interacting with patients, or use of patient records. Our findings support that registries requiring data entry could be widely adopted into routine clinical practice.

Purpose: To identify and assess the quality of questionnaires used to measure quality of life in keratoconus and guide selection of the most appropriate questionnaire for evaluating the impact of keratoconus., Methods: A literature search was carried out in Scopus, Web of Science, PubMed, MEDLINE, Cochrane, and PsycINFO databases. Articles that described a questionnaire to measure quality of life in keratoconus were included. Information on psychometric properties and validity was extracted and analyzed based on a set of quality criteria. Finally, the impact of keratoconus and its management methods on quality of life was reviewed., Results: The search yielded 331 publications, of which 45 articles describing 18 (12 ophthalmic including 2 keratoconus-specific and 6 generic) questionnaires were reviewed. Most of the articles (40, 88.9%) described ophthalmic questionnaires not specific to keratoconus. The National Eye Institute Visual Function Questionnaire was the most frequently used questionnaire (n = 26). Only 4 articles provided information on psychometric properties. The Keratoconus Outcomes Research Questionnaire, the only validated keratoconus-specific questionnaire, had the most superior psychometric properties. However, it consists of items on only 2 domains of quality of life (activity limitation and symptoms). Overall, keratoconus management methods (spectacles, contact lenses, and cross-linking in early stages, corneal transplantation in late stages) improved quality of life. The quality of life scores were associated with clinical measures including visual acuity, corneal topography, pachymetry, and keratoconus severity., Conclusions: There is a need for a comprehensive and high-quality patient-reported outcome measure in keratoconus. A questionnaire should be chosen based on the purpose and the quality of the questionnaire. This review guides selection of an appropriate questionnaire.

Purpose: The aim of this study was to evaluate the psychometric properties of the Keratoconus Outcomes Research Questionnaire (KORQ) in patients enrolled in the Save Sight Keratoconus Registry., Methods: A cross-sectional study was conducted utilizing prospectively collected web-based registry data. The psychometric properties of the KORQ were assessed using both classical test theory and Rasch analysis. Andrich group rating scale variant of the Rasch analysis was conducted using Winsteps software, Version 3.92.1., Results: The KORQ was completed by 189 patients with keratoconus (men, 67.7%; white, 69.8%; median age 29 years; better eye median values: visual acuity, 75 LogMAR letters; Kmax, 51.3 D; K2, 46.5 D; thinnest pachymetry, 485 μm). Cronbach's α for the "Activity Limitation" and "Symptoms" scales were 0.95 and 0.91, respectively, with both scales free from floor or ceiling effects. On Rasch analysis, the category thresholds were ordered and well-spaced for both scales. The Activity Limitation scale had excellent psychometric properties including person separation index (3.6), unidimensionality (variance explained, 65.4%), fit statistics (<1.3 MnSq), and measurement range (3.6 logits). Similarly, the Symptoms scale had satisfactory psychometric properties including person separation index (2.5), unidimensionality (variance explained, 54.3%), fit statistics (<1.30 MnSq except for 1 item), and measurement range (2.0 logits). Both scales were well targeted to the population and free of differential item functioning., Conclusions: The KORQ is a psychometrically robust patient-reported outcome measure for evaluating quality of life parameters in keratoconus. It enables routine collection and monitoring of meaningful patient-reported outcome data in clinical settings, including registries.

Purpose: To assess vision-related quality of life using the Impact of Vision Impairment Questionnaire (IVI) in patients with keratoconus enrolled in the Save Sight Keratoconus Registry., Methods: In this cross-sectional study, data on 107 keratoconic patients were collected through a prospectively designed web-based registry from a quaternary referral eye hospital and 2 corneal subspecialty practices. Vision-related quality of life was evaluated using the IVI. Rasch analysis was used to transform the IVI responses into interval-level measures comprising reading, mobility, and emotional well-being subscales. Associations between best-corrected visual acuity (BCVA), maximum simulated keratometry (Kmax), steep keratometry (K2), and pachymetry for each eye and IVI subscale scores were evaluated with univariate (Pearson correlations) and multivariable regression adjusted for age and gender., Results: Of the 107 patients, 37 (34.5%), 41 (38.0%) and 29 (26.9%) had mild, moderate, and severe keratoconus, respectively. On uni- and multivariable analysis, BCVA in the better eye had the strongest association with reading [r = 0.51; 95% confidence interval (CI), 0.35-0.64, P = 0.004] and mobility (r = 0.55; 95% CI, 0.41-0.67, P < 0.001) subscale scores. BCVA in the better and worse eye, both had the joint strongest associations with emotional scores on univariate analysis, but only the latter was significant on multivariable analysis (r = 0.37; 95% CI, 0.20-0.53, P < 0.001). K2 and Kmax in the better eye also displayed significant associations with reading and mobility scores., Conclusions: In patients with keratoconus, BCVA in the better eye had the strongest correlation with reading and mobility scores, whereas BCVA in the worse eye was significantly correlated with emotional scores.

It is thought that corneal epithelial injuries resolve by leading-edge cells "sliding" or "rolling" into the wound bed. Here, we challenge this notion and show by real-time imaging that corneal wounds initially heal by "basal cell migration." The K14CreER T2 -Confetti multi-colored reporter mouse was employed to spatially and temporally fate-map cellular behavior during corneal wound healing. Keratin-14 + basal epithelia are forced into the wound bed by increased population pressure gradient from the limbus to the wound edge. As the defect resolves, centripetally migrating epithelia decelerate and replication in the periphery is reduced. With time, keratin-14 + -derived clones diminish in number concomitant with their expansion, indicative that clonal evolution aligns with neutral drifting. These findings have important implications for the involvement of stem cells in acute tissue regeneration, in key sensory tissues such as the cornea., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Our objective was to investigate the hypothesis that women on adjuvant aromatase inhibitors (AIs) for treatment of breast cancer have a higher prevalence of dry eye syndrome (DES) compared with controls., Materials and Methods: Exposure and control groups were recruited. A cross sectional questionnaire-based study was performed. Demographic data and medical histories were collected. The presence of dry eye syndrome was determined by the ocular surface disease index (OSDI). The Functional Assessment of Cancer Treatment - Endocrine Subscale (FACT-ES) was performed to investigate correlations with other side effects of AIs., Results: 93 exposure group and 100 control group questionnaires were included. The groups were similar in all demographic variables. The prevalence of dry eye syndrome was 35% (exposure) and 18% (control) (p < 0.01, OR 2.5). AIs were the only factor associated with dry eyes. The OSDI score was negatively correlated with the total FACT-ES score and positively correlated with duration of treatment., Conclusion: Our study is the first to use a validated questionnaire to assess for DES in this population. DES is significantly more prevalent in women on AIs compared with controls. This is a newly emerging, and easily treated side effect of AIs. Self-reporting of dry eye symptoms underestimates the prevalence of DES with AIs. We recommend routine screening of patients on AIs with the OSDI with the aim of improving patient quality of life and possibly adherence., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

We have used laser irradiation to enhance the natural adhesiveness of chitosan to form a thin film surgical adhesive. Prevention of infection at surgical sites often utilizes systemic provision of antibiotics with reduced local efficacy and potential side effects. In the work reported here, we investigate the bactericidal properties of laser-irradiated chitosan films and their impregnation with the antibiotic vancomycin. Despite strong efficacy in solution, chitosan films showed no antimicrobial activity against representatives of common pathogens Escherichia coli , Staphylococcus aureus , and S. epidermidis . In contrast, a composite of chitosan adhesive and the antibiotic vancomycin showed therapeutically significant release profiles greater that the Minimum Bactericidal Concentrations (MBCs) for the Staphylococci over a 28 day period. These composite films had greater crystallinity, up to 28 ± 3 compared to 8.9 ± 2%, for its unblended counterpart. Despite a significant increase in material strength from 31.4 ± 4 to 77.5 ± 5 MPa, flexibility was still maintained with an elongation to break around 5 ± 2% and fold endurance of approximately 30 ± 3-folds. Laser irradiation had no apparent effect on the release or activity of the antibiotic which survived transient temperatures at the film-tissue interface during infrared irradiation of around 54 °C. Furthermore, significant adhesive strength was still apparent, 15.6 ± 2 KPa. Thus, we have developed a laser-activated bioadhesive with the potential to close wounds while facilitating the prevention of microbial infection through local release of antibiotic targeted to the site of potential infection.