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We aimed to determine the long-term outcomes of epithelium-off cross-linking (CXL) in keratoconus patients.An observational registry study from 41 centres across 5 countries was carried out. Primary outcomes included the mean change in visual acuity (VA), Kmax, K2, and thinnest corneal thickness (TCT) at 1-5 years. Secondary outcomes included the percentage of eyes with worsening, stable and improving outcomes.There were 976 eyes of 794 patients with 1-year of complete follow-up, 501 eyes with 2-years, 355 with 3-years, 235 with 4-years and 162 with 5-years. There was a significant improvement in mean VA from baseline by 3.7 logMAR letters (p 0.001) in year 1, and 6.9 (p 0.001) in year 5. Mean Kmax decreased by 1.2 dioptres (D; p 0.01) in year 1. During subsequent years the Kmax flattening appeared sustained but this was not statistically significant. K2 flattened significantly from baseline in year 1 and then remained stable. At 1 year, 4.1% patients were poor responders to CXL in terms of VA, losing ≥15 letters. The proportion of the poor responders remained unchanged: 4.9% at 5-years. The proportion of poor responders in terms of Kmax remained similar: 5.9% steepening by ≥2D at 1-year and 7.5% at 5-years. The proportion of K2 poor responders remained stable with 4.7% steepening by ≥2D at 1-year and 5.8% at 5-years.Cross-linking is effective at stabilising keratoconus up to 5 years in most patients. However, a small proportion of eyes failed to stabilise and had reduced vision.

International audience; PurposeTo 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 100 μm induced a hyperopic shift. Metaregressions did not demonstrate differences between the 3 groups (100 μm.

To compare the repair of penetrating corneal incisions in an in vivo rabbit model using a laser-activated thin-film adhesive, sutures, or self-seal.The University of Sydney, Camperdown, Australia.Animal studies.Under an operating microscope, 2.0 mm penetrating incisions were created in 162 right eyes. Incisions in one group were repaired with the adhesive, the second group received a single 10-0 nylon suture, and the third group was left to self-seal. Rabbits were killed humanely at predetermined timepoints over 2 weeks, and wound healing was assessed using burst pressure and immunohistological studies. A modified McDonald-Shadduck scoring was used to assess eyes.The mean burst pressure of the adhesive group was significantly higher than the sutured or self-sealed groups at all timepoints within the first 72 hours. At 0 hour, the burst pressure was 98.0 (±17.0) mm Hg, 30.6 (±2.1) mm Hg, and 3.8 (±0.6) mm Hg (P.00001) for adhesive-treated (n = 5), sutured (n = 5), and self-sealed wounds (n = 5), respectively. These increased to 229.0 (±53.7) mm Hg, 12.4 (±2.9) mm Hg, and 27.3 (±4.0) mm Hg (P = .0011) at 72 hours. The modified McDonald-Shadduck score was significantly higher for eyes repaired using the adhesive than those sutured or left to self-seal for the first 72 hours. On histology and immunofluorescence, adhesive treatment demonstrated better wound approximation and higher myofibroblastic activation than the other groups.The adhesive was efficacious in sealing penetrating corneal incisions and tolerated higher burst pressures than sutures or self-seal. The adhesive was biocompatible in rabbits, and incisions demonstrated a rapid gain in wound strength that sustained over the study period.

N-acetylcysteine (NAC) was first discovered as a mucolytic agent in 1960. We investigate the role of topical NAC in ocular therapeutics, including its mechanism of action, current applications, and adverse effects. A systematic search of peer-reviewed articles identified 106 references including in vitro, in vivo and clinical studies on the use of NAC in the treatment of ocular diseases. NAC can be synthetically manufactured, and its mechanisms of action include mucolysis, scavenging hydroxyl radicals, and modulation of inflammatory cascades. These unique properties contribute to the diverse applications of NAC, including its steroid-sparing potential. NAC has been used topically in the treatment of corneal wounds, chemical injuries, keratitis, dry eye disease and meibomian gland dysfunction. The clinical benefits of NAC are evident over a wide range of concentrations, the most common being 5-10% topical NAC applied four times daily. Adverse effects such as corneal necrosis are rare, but have been reported with higher doses. NAC also has potential applications in laser epithelial keratomileusis, diabetic eye disease, retinitis pigmentosa, senile nuclear cataracts, macular degeneration, and cigarette smoke-induced corneal damage. Recently, chitosan-NAC has been used as a nanocarrier for the topical administration of medications to the ocular surface. Owing to its potent antioxidant, anti-inflammatory and mucolytic properties, topical NAC has had extensive use in the treatment of ocular pathology.

The objectives of this study were to evaluate the quality-of-life (QoL) impact of eye diseases (keratoconus; neovascular age-related macular degeneration, AMD; retinal vein occlusion, RVO; and diabetic macular edema, DME) using the Impact of Vision Impairment (IVI) questionnaire, and to determine the relationship between the IVI scores and visual acuity.This cross-sectional, multicentre, real-world study utilised the prospective, web-based Save Sight Registries. The IVI was completed by 1557 patients: 307 with keratoconus, 1049 with AMD, 148 with RVO and 53 with DME. Statistical analysis included Rasch analysis, Welch t-test, one-way ANOVA, Tukey's test, Pearson correlation, and multiple regression.The IVI scales (Overall; Visual Function, VF; Emotional, EM) had robust psychometric properties. The keratoconus patients had the worst Overall (adjusted mean: 48.2 vs. DME 58.8, RVO 64.6, AMD 67.6 units), VF (47.7 vs. DME 59.4, RVO 65.9, AMD 68.9 units) and EM (50.8 vs. DME 63.1, RVO 69.2, AMD 71.8 units) scores (all p 0.05). The IVI scales scores weakly correlated with better and worse eye visual acuity (Pearson's r 0.24-0.39, all p 0.05). The correlations were similar in the better eye (Overall 0.35, VF 0.39, EM 0.24) and the worse eye (Overall 0.31, VF 0.33, EM 0.25) visual acuity. Correlations with visual acuity were stronger for VF than for the EM scores.The IVI was a psychometrically robust QoL questionnaire. Keratoconus patients had worse IVI scores than patients with retinal diseases. The low strength of correlations between visual acuity and QoL scores, although statistically significant, suggested that a complex relationship exists.

Purpose Describe presumed microbial keratitis cases resulting in evisceration/enucleation from 2012 to 2016 in Sydney, Australia. Methods A retrospective case review included 33 patients. Cases were identified from pathology and hospital coding data. Sociodemographic and clinical details were collated. Results Mean age was 79 years (range: 38-100 years), and 64% female. There were 30 eviscerations and 3 enucleations, at a median time of 8 days (range: 1-270 days) due to endophthalmitis (n = 15, 45%). Major ocular associated factors included topical corticosteroid use in 12 patients (36%), exposure keratopathy in 4 (12%), ectropion in 3 (9%), degenerative corneal disease in 3 (9%), and corneal graft in 2 (6%). Pseudomonas aeruginosa was the most common isolate with no reports of antimicrobial resistance. Conclusions Educating elderly patients with a history of topical corticosteroid use, corneal or ocular surface disease about prompt hospital presentation and treatment of microbial keratitis may decrease the probability of losing the eye.

Ophthalmic trauma is a leading cause of preventable monocular blindness worldwide. The prevalence of ophthalmic trauma varies considerably based on geographic location, socio-economic status, age groups, occupation, and cultural practices such as firework celebrations. Clinical registries are known to be valuable in guiding the diagnosis, management, and prognostication of complex diseases. However, there is currently a lack of a centralized international data repository for ophthalmic trauma. We draw lessons from past and existing clinical registries related to ophthalmology and propose a new suitable international multicenter clinical registry for ophthalmic trauma: the International Globe and Adnexal Trauma Epidemiology Study (IGATES). IGATES is hosted on a secure web-based platform which exhibits user-friendly smart features, an integrated Ocular Trauma Score (OTS) prognosis calculator, efficient data collection points, and schematic graphical software. IGATES currently has 37 participating centers globally. The data collected through IGATES will be primarily used to develop a more robust and improved ophthalmic trauma prognostic classification system, the Ocular Trauma Score-2 (OTS-2), which builds on previous systems such as the Birmingham Eye Trauma Terminology System (BETTS) and Ocular Trauma Score (OTS). Furthermore, IGATES will act as a springboard for further research into the epidemiology, diagnosis, and management of ophthalmic trauma. Ultimately, IGATES serves to advance the field of ophthalmic trauma and improve the care that patients with ophthalmic trauma receive.

To report on the factors associated with severe vision loss from fireworks-related ocular trauma during celebrations, including festivals. Tertiary eye care hospitals in 5 countries and private ophthalmology practices in the Netherlands. Patients included received treatment for fireworks-related ocular trauma during celebrations. Demographic and clinical data for patients affected were analyzed and associations with severe vision loss reported. Of 388 patients, 71 (18.3 %) had severe vision loss (worse than 6/60) at 4-week follow-up due to fireworks-related ocular trauma. Mean age overall was 20.6 years (range 2 to 83 years), and there was a male predominance of 4:1. Clinical factors associated with severe vision loss included penetrating injury (OR 4.874 [95% CI 1.298–18.304; p = 0.02]) and lens injury (OR 7.023 [95% CI 2.378–20.736; p = 0.0004]). More patients with closed-globe injuries (CGIs) had improved vision after 4 weeks (OR 3.667, 1.096–12.27) compared to those with open-globe injuries (OGI) (p = 0.035). Eye protection use was reported by 7 patients, and 39.4% patients < 18 years were unsupervised by an adult at the time of injury. Severe vision loss from fireworks-related ocular trauma occurred during celebrations in a variety of countries and was associated with penetrating and/or lens injury and poor presenting vision. New initiatives are needed to prevent severe vision loss associated with these injuries.

The purpose of this study was to describe demographics, predisposing factors, clinical features, treatment, and outcomes of microbial keratitis cases resistant to antimicrobials.A retrospective case series was conducted. All patients with microbial keratitis resistant to antimicrobials who underwent a corneal scrape and culture from 2012 to December 2016 at the Sydney Eye Hospital were included. Cases were identified from pathology and hospital coding data. Coagulase-negative staphylococci (CoNS), Staphylococcus aureus (S. aureus), and Corynebacterium spp. resistant to cefalotin, chloramphenicol, ciprofloxacin, or gentamicin were analyzed.One hundred fifteen episodes had a resistant CoNS, 24 S. aureus, and 12 Corynebacterium spp. Antimicrobial resistance was associated with older women (67%, median age 83 years) with Corynebacterium spp. (P0.001), corneal graft, and previous topical steroid use. Larger epithelial defects (P = 0.203) and infiltrates (P = 0.180) were more likely to be associated with Corynebacterium spp., but not statistically significant. At the initial and final visits, resistant S. aureus (75% vs. 67%) and Corynebacterium spp. (78% vs. 80%) cases were more likely to be classified as blind (3/60) compared with CoNS (45% vs. 28%) (P = 0.011 vs. P = 0.004). Corneal perforation occurred more often in resistant S. aureus cases (P0.001), whereas slow and nonhealing epithelial defects needing other procedures were more likely to occur with resistant Corynebacterium spp. (P0.001).Patients with resistant CoNS were younger and presented with smaller ulcers and moderate vision loss. Visual and clinical outcomes were significantly better for resistant CoNS than for those with resistant S. aureus or Corynebacterium spp.

Introduction Ocular trauma can cause significant morbidity and is a leading cause of unilateral blindness. In multi-trauma, life- and sight-threatening injuries can co-occur causing increased complexity in the assessment and management of ocular injuries as the competing priorities in the severely injured must be balanced. We conducted a narrative review to determine how ophthalmology may be further integrated into a trauma service and/or the organisation of an ocular trauma service. Methods The literature was reviewed via EMBASE, MEDLINE, CINAHL and Google Scholar utilising comprehensive search strategies and keyword searches. Our review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results The search yielded 437 articles, 30 studies met selection criteria and were included in the review. The included literature comprised guidelines, observational studies and reviews of registry data from Australia, England, the United States, Singapore, Iran and Israel. Conclusion The Australian Trauma Model has clear guidelines for referral of trauma patients to ensure appropriate care of the severely injured. However, there are no clear guidelines for the integration of ophthalmology into trauma. Therefore, early referral to ophthalmology and streamlining of referral pathways of specialist care would improve the care of patients with ocular trauma.

To detail the methodology for a novel ocular trauma registry and utilize the registry to determine the demographics, nature of injury, and associations of severe visual loss for open globe injuries (OGI). Thirteen hospitals in 7 countries used International Globe and Adnexal Trauma Epidemiology Study (IGATES) platform. Patients presenting between April 2009 and 2020 with OGI (with or without) adnexal involvement or intraocular foreign body (IOFB) were included. Analyses of presenting and final VA, using “severe vision loss” (VA ≤ 6/60) and “no severe loss” (VA > 6/60), were performed. Four hundred fifty-four (64%) patients had VA

There is increasing focus on the value of real-world clinical registry data in multiple medical disciplines, including ophthalmology. However, disease-focused clinical registries that engage optometrists are rare. This paper introduces the Optometry Module of the Save Sight Keratoconus Registry (SSKR) and highlights the potential advantages it can offer to optometrists for improving their quality of patient care and for engaging in research. Optometrists are primary eye care providers and have a major role in providing clinical care to people with keratoconus. The SSKR system has been developed to collects high-quality information on essential clinical parameters including patient-reported outcomes (i.e., quality of life data). The real-world data from the Optometry Module of the SSKR can be analysed to obtain insights into contemporary optometry keratoconus practice, and be used to identify opportunities for improving clinical care. Optometrists' engagement with the registry supports reflective clinical practice through real-time benchmarking. Optometrists can use the registry system to track patient outcomes, and it provides a framework for educating patients about their keratoconus journey. The system also captures details relating to patient adverse events, with subsequent data analysis enabling risk factors for such events to be identified. In summary, the Optometry Module of the SSKR captures real-world clinical evidence that has the potential to inform practice improvement, facilitate safety surveillance and enable outcomes research in keratoconus, all with the ultimate intent of enhancing care for people living with keratoconus.

International audience; Purpose: To evaluate the outcome of SPOT scleral lenses in the management of irregular astigmatism in patients with corneal ectasia and penetrating keratoplasty. Second, we analyzed patients' characteristics and tolerance, comfort, and geometries of fitted lenses.Method: Over a 5-year period, we included patients experiencing irregular astigmatism fitted with SPOT scleral contact lenses, from the University Hospital of Clermont-Ferrand, France. Data collected included corneal diseases, refractive error, best-corrected visual acuity (VA) with SPOT lenses, geometry of the lens, number of adjustment consultations, and the duration of follow-up. Comfort, quality of vision, less handling, and satisfaction were evaluated using visual analog scales after a 6-month follow-up period.Results: Sixty-five patients were included, analyzing 107 eyes. Eighty percent of patients still daily wore lenses after a follow-up of 22.3±13.8 months. Visual acuity improved by 0.47±0.51 logarithm of the minimum angle of resolution (average increase of 5 lines) (P75/100). Contact lenses were daily worn 10.0±4.1 hr/day. Most patients wore size M (17 mm) lenses (53.3% of patients), with an average sagittal height of 5.2±1.2 mm. Internal toricity was used in 30% of cases. Best geometry was found after 2.69±0.87 consultations.Conclusion: SPOT scleral contact lenses are an effective and well tolerated method to improve the VA of patients with irregular astigmatism.

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.

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

International audience; urposeTo evaluate the efficacy of preventive treatment against allograft rejection after endothelial keratoplasty (EK), we conducted a systematic review and meta-analysis.MethodPubMed, Cochrane Library, Embase and ScienceDirect databases were searched until May 2021. We computed a random-effect meta-analysis on graft rejection rate stratified by the intervention (i.e. Descemet membrane EK (DMEK) and Descemet stripping (Automated) EK (DS(A)EK) or ultrathin (UT)-DSAEK), and postoperative treatment. Meta-regressions were performed to compare intervention, treatment and influence of putative confusion factors.ResultsWe included 49 studies and 12 893 EK (6867 DMEK and 6026 DS(A)EK/UT-DSAEK). Topical steroids were merged in two efficacy regimens: standard steroids (prednisolone acetate 1% or dexamethasone 0.1%) and soft steroids (fluorometholone 0.1% or loteprednol etabonate 0.5%). Globally, DMEK had a lower graft rejection rate than DS(A)EK/UT-DSAEK (coefficient − 3.3, 95 CI, −4.60 to −1.90; p

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.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.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.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.

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

To review the use of clinical corneal sealants for the closure of full thickness corneal wounds.A systematic review was conducted across CENTRAL, Medline, PubMed, Embase, Scopus, mRCT and ICTRP for the keywords of 'cornea', 'full-thickness wound', 'sealant' and their synonyms. Only evidence level 2 of higher as graded by Oxford Centre of Evidence-based Medicine were included for this review.Seven studies were included; three randomized controlled trials investigated ReSure® sealant, 2 OcuSeal®, 1 human fibrin glue vs cyanoacrylate and 1 human fibrin glue as an adjunct to sutures vs sutures alone in penetrating keratoplasty. ReSure® was superior to suture for sealing leaking corneal incisions after cataract surgery despite provocation. ReSure® sealant has not been tested on complex full thickness corneal wounds, perforated ulcers or penetrating keratoplasty. OcuSeal® was also able to seal full thickness cornea wound post-cataract surgery to prevent ingress of Trypan blue dye. Human fibrin glue and cyanoacrylate were similarly effective in treating corneal perforations3 mm of mixed etiologies.There are limited high-level evidence for corneal sealants. The currently available sealants with human data are ReSure®, OcuSeal®, human fibrin glue and cyanoacrylates. While ReSure® and OcuSeal® are effective post-cataract surgery, there are no data for perforations from other etiologies. Post-approval data from ReSure® registry report good tolerability and no apparent safety concerns.

Purpose Inclusion of the preservative benzalkonium chloride (BAC) in ophthalmic solutions is prevalent, despite the noted potential for exacerbating dry eye disease (DED). Whilst studies incorporating BAC have assessed its’ effects as a mouse model of DED, the impact on limbal epithelia is under-studied. Our investigation aimed to comprehensively assess the impact of different BAC dosing regimens and their suitability as a mouse model of DED. Methods C57BL/6J mice (n = 72) were administered topical BAC (0.05–0.2%) over 7 days. Fluorescein staining, corneal smoothness index, and immuno-histological analyses were applied to determine architectural and cellular changes on the ocular surface following BAC treatment. The effect of BAC (0.0001–0.01%) on cultivated primary mouse corneo-limbal epithelial cells (CLECs) (n = 6) was examined using morphological and functional assays. Results Whilst 0.2% BAC induced severe corneal epithelial defects, 0.1% BAC dispensed once daily over 7 days, induced punctate fluorescein staining without detriment to corneal smoothness. Histochemical staining revealed disorganized basal corneal epithelial cells with enlarged cytoplasmic halos. Furthermore, PAS+ goblet cells were decreased. BAC treatment also modulated K14 expression and distribution within the limbus. In cultured CLEC, BAC triggered cell contraction and vacuolation, increased LDH release and elevated cell necrosis by 4.1-fold. Concentrations of BAC as low as 0.0001% decreased colony formation. Conclusions This study describes how exposing C57BL/6 mice to BAC induce some clinicopathological features of DED seen in humans, and therefore provides the foundations to explore the consequences on the ocular surface, particularly on limbal epithelia and its’ stem cells.

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.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.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.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.

Findings from this study examining Australian optometrists’ insights into ocular stem cell (SC) therapies have capacity to inform continuing professional development (CPD) about these interventions. This study investigated Australian optometrists’ knowledge, views, experiences, and preferred education sources regarding ocular SC therapies. An online survey was distributed to optometrists via Optometry Australia, Mivision magazine, professional groups, and social media from August 2020 to March 2021. Data were collected on demographics, and SC knowledge, awareness and experience. Of 81 optometrists who completed the survey, many were metropolitan-based (85%), worked in independent practice (47%), female (56%) and >46 years of age (45%). Approximately one-fifth indicated awareness of ocular SC therapies used in standard practice; one-third had knowledge of SC clinical trials. The most noted SC therapies were for corneal disease in the United States [US] (72%) and Australia (44%). Respondents identified the availability of SC therapies for dry eye disease in Australia and the US (39% and 44% respectively), despite no regulatory-approved treatments for this indication. Clinical trials investigating inherited retinal and corneal diseases in Australia were the most commonly identified (44% and 36%, respectively). Half the respondents felt ‘unsure’ about the quality of evidence for treating eye conditions using SCs. One-fifth indicated concerns with these therapies; of these, most mentioned efficacy (82%), safety (76%) and/or cost (71%). About one-fifth reported being asked for advice about SCs by patients. Two-thirds felt neutral, uncomfortable, or very uncomfortable providing this advice, due to lack of knowledge or the topic being beyond their expertise. Over half (57%) were unsure if clinical management should change if patients received SC therapies. Respondents were receptive to face-to-face education. Some optometrists responding to this survey were aware of ocular SC therapies and/or clinical trials. CPD programs may assist with maintaining currency in this evolving field.

Background:In microbial keratitis, infection of the cornea can threaten vision through permanent corneal scarring and even perforation resulting in the loss of the eye. A literature review was conducted by Karsten, Watson and Foster (2012) to determine the spectrum of microbial keratitis. Since this publication, there have been over 2600 articles published investigating the causative pathogens of microbial keratitis.Objective:To determine the current spectrum of possible pathogens implicated in microbial keratitis relative to the 2012 study.Methods:An exhaustive literature review was conducted of all the peer-reviewed articles reporting on microbial pathogens implicated in keratitis. Databases including MEDLINE, EMBASE, Scopus and Web of Science were searched utilising their entire year limits (1950-2019).Results:Six-hundred and eighty-eight species representing 271 genera from 145 families were implicated in microbial keratitis. Fungal pathogens, though less frequent than bacteria, demonstrated the greatest diversity with 393 species from 169 genera that were found to cause microbial keratitis. There were 254 species of bacteria from 82 genera, 27 species of amoeba from 11 genera, and 14 species of virus from 9 genera, which were also identified as pathogens of microbial keratitis.Conclusion:The spectrum of pathogens implicated in microbial keratitis is extremely diverse. Bacteria were most commonly encountered and in comparison, to the review published in 2012, further 456 pathogens have been identified as causative pathogens of microbial keratitis. Therefore, the current review provides an important update on the potential spectrum of microbes, to assist clinicians in the diagnosis and treatment of microbial keratitis.

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.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/cm2 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.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 of2% 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.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.

The objective of this study was to undertake a systematic review of the literature reporting on clinical registries in dry eye disease (DED).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.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.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.

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.

International audience; PurposeManagement of NK can be difficult, involving a range of treatments with variable efficacy. We conducted a systematic review and meta-analysis to evaluate the efficacy of medical and surgical treatments for neurotrophic keratitis (NK).MethodPubMed, Cochrane Library, Embase, ClinicalTrial.gov, and ScienceDirect were searched for studies assessing efficacy of NK treatments. We computed random-effect meta-analyses on corneal healing, time to complete healing, and visual acuity changes between baselines and after treatment, stratified on treatment classes. We followed the PRISMA guidelines (registration number CRD42021225721).ResultsWe included 20 studies: 571 patients and 5 treatment classes (2 surgical and 3 non-surgical). The percentage of patients with complete corneal healing did not differ between specific treatments (nerve growth factor eyedrops (NGF), 75%, 95CI 46 to 104%; autologous serum (AS), 92%, 86 to 98%; neurotization, 99%, 95 to 103%; amniotic membrane transplantation (AMT), 86%, 78 to 94%). All specific treatments had better percentage of complete healing (p

International audience; BackgroundIn this systematic review and meta-analysis, we aimed to compare deep learning versus ophthalmologists in glaucoma diagnosis on fundus examinations.MethodPubMed, Cochrane, Embase, ClinicalTrials.gov and ScienceDirect databases were searched for studies reporting a comparison between the glaucoma diagnosis performance of deep learning and ophthalmologists on fundus examinations on the same datasets, until 10 December 2020. Studies had to report an area under the receiver operating characteristics (AUC) with SD or enough data to generate one.ResultsWe included six studies in our meta-analysis. There was no difference in AUC between ophthalmologists (AUC = 82.0, 95% confidence intervals [CI] 65.4–98.6) and deep learning (97.0, 89.4–104.5). There was also no difference using several pessimistic and optimistic variants of our meta-analysis: the best (82.2, 60.0–104.3) or worst (77.7, 53.1–102.3) ophthalmologists versus the best (97.1, 89.5–104.7) or worst (97.1, 88.5–105.6) deep learning of each study. We did not retrieve any factors influencing those results.ConclusionDeep learning had similar performance compared to ophthalmologists in glaucoma diagnosis from fundus examinations. Further studies should evaluate deep learning in clinical situations.

Statins are effective and well-tolerated hypolipidaemic agents which have been increasingly studied for their pleiotropic immunomodulatory and anti-inflammatory effects. Statins have potential therapeutic benefit in a range of neuro-ophthalmological conditions but may also induce or exacerbate certain neurological disorders. This literature review examines evidence from clinical and in vitro studies assessing the effects of statins in myasthenia gravis, myopathy, multiple sclerosis, neuromyelitis optica, idiopathic intracranial hypertension (pseudotumour cerebri), migraine, giant cell arteritis, Bell's palsy, ocular ischaemia, stroke, Alzheimer's disease and Parkinson's disease.

Purpose The purpose of this study was to investigate whether laser irradiation, used to activate an adhesive for sealing penetrating corneal incisions, causes any ophthalmoscopically or histologically visible retinal changes. Methods Baseline fundus assessment was conducted prior to laser irradiation of eyes of pigmented Dutch Belted rabbits. Treatment group was 18 eyes with the corneal adhesive activated in situ by a near infrared laser (125 mW for 45 seconds). The positive control group was 18 eyes, each irradiated for 60 seconds at 375, 500, 625, and 750 mW at different retinal locations. Unexposed regions of the retina were used as negative internal control. Ophthalmoscopic assessment was conducted immediately after laser exposure and prior to euthanasia. Retinas were histologically assessed at 0, 3, 72, and 168 hours after treatment. Results No ophthalmoscopically or histologically visible retinal changes were observed in the treatment group immediately, nor up to 168 hours after laser irradiation. In the positive control group, the incidences of ophthalmoscopically visible retinal lesions increased with irradiation power: 5.6% at 375 mW, 16.7% at 500 mW, 44.4% at 625 mW, and 50% at 750 mW. Histologically, retinal damage was observed as coagulative necrosis to all layers of the neural retina, including the retinal pigment epithelium. Conclusions The laser irradiation process used in the corneal adhesive technology did not cause any ophthalmoscopically or histologically visible retinal changes in the in vivo pigmented rabbit model. Prolonged exposure with this laser and at higher power can cause coagulative necrosis to the retina. Translational relevance The corneal adhesive can be applied in humans without causing laser retinal damage.

Purpose To report anti-viral therapy and outcomes for patients with herpes simplex keratitis (HSK) in a quaternary centre in Sydney, Australia. Methods A retrospective case review of patients who received anti-viral medications for any form of HSK was conducted. Cases were identified from pathology results, pharmacy records and hospital coding data from 2012 to 2013. Clinical details including initial anti-viral treatment and outcome were collated from the medical records. Outcome was determined from when initial anti-viral treatment was stopped or changed, and classified as either clinically resolved, partially resolved or worsened for therapeutic indication; or as either success or failure for prophylaxis. Results Anti-viral therapy was given for therapeutic and prophylactic indications at presentation in 252 (85%) and 44 patients (15%), respectively. Topical aciclovir five times daily and valaciclovir in doses ranging from 500 mg to 1 g, one to three times daily were the preferred anti-viral therapies. One hundred and fourteen patients (n = 114/296, 38.5%) also received topical corticosteroids. An outcome was determined for 210/296 (71%) patients. For therapeutic indication, half of the patients (90/174) partially resolved within 8 days, with best outcomes achieved for endothelial HSK (8/11, 73%) and keratouveitis (21/36, 58%). Adverse events, observed in 20% (35/174) of patients, included corneal perforation (n = 8) and secondary bacterial keratitis (n = 6). Prophylaxis with antiviral therapy was successful in two-thirds of patients after 6 months. Conclusions Clinical and visual outcomes varied with the type of HSK and prescribed therapies. Diverse initial anti-viral therapies were identified; standardising them may improve outcomes.

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.