Intereye Asymmetry as a Predictor of Progression in Patients With Untreated Keratoconus: Findings From a Longitudinal Study.

PURPOSE: The purpose of this study was to evaluate interocular predictors of progression in patients with untreated keratoconus. METHODS: This is a multicenter longitudinal observational study with real-world data collected through the Save Sight Keratoconus Registry. Patients between the period of June 2000 and September 2022 were included in this study. Parameters such as patient age, sex, ocular history, visual acuity, K2, Max-K, and thinnest corneal thickness pachymetry (TCT) were analyzed. RESULTS: There were 4342 untreated eyes from 2171 patients with keratoconus. A total of 333 patients showed progression of either Max-K, TCT, or both, whereas 1838 patients showed stable parameters. Factors associated with a higher incidence of progression in Max-K were younger baseline age (HR 0.96 per year older; 95% CI 0.95-0.98, P < 0.0001) and a higher baseline intereye asymmetry in Max-K (HR 1.02 per higher diopter; 95% CI 1.00-1.04, P = 0.04). A younger baseline age was the only predictor of progression in TCT (HR 0.97 per year older; 95% CI 0.95-0.99, P = 0.001). CONCLUSIONS: Age is the most significant predictor of progression for both corneal thinning and progression of Max-K. Interocular asymmetry in Max-K at baseline could be used as part of an algorithm for determining the risk of keratoconus progression. It is recommended that patients with higher interocular asymmetry in Max-K have a closer follow-up of both eyes as they are at a higher risk of progression.

Intravitreal therapeutic nanoparticles for age-related macular degeneration: Design principles, progress and opportunities.

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. The current standard treatment for AMD involves frequent intravitreal administrations of therapeutic agents. While effective, this approach presents challenges, including patient discomfort, inconvenience, and the risk of adverse complications. Nanoparticle-based intravitreal drug delivery platforms offer a promising solution to overcome these limitations. These platforms are engineered to target the retina specifically and control drug release, which enhances drug retention, improves drug concentration and bioavailability at the retinal site, and reduces the frequency of injections. This review aims to uncover the design principles guiding the development of highly effective nanoparticle-based intravitreal drug delivery platforms for AMD treatment. By gaining a deeper understanding of the physiology of ocular barriers and the physicochemical properties of nanoparticles, we establish a basis for designing intravitreal nanoparticles to optimize drug delivery and drug retention in the retina. Furthermore, we review recent nanoparticle-based intravitreal therapeutic strategies to highlight their potential in improving AMD treatment efficiency. Lastly, we address the challenges and opportunities in this field, providing insights into the future of nanoparticle-based drug delivery to improve therapeutic outcomes for AMD patients.

Corneal neuropathic pain: a review to inform clinical practice.

Corneal neuropathic pain (CNP) is a poorly defined disease entity characterised by an aberrant pain response to normally non-painful stimuli and categorised into having peripheral and central mechanisms, with the former responding to instillation of topical anaesthetic. CNP is a challenging condition to diagnose due to numerous aetiologies, an absence of clinical signs and ancillary tests (in vivo confocal microscopy and esthesiometry), lacking the ability to confirm the diagnosis and having limited availability. Symptomatology maybe mirrored by severe and chronic forms of dry eye disease (DED), often leading to misdiagnosis and inadequate treatment. In practice, patients with suspected CNP can be assessed with questionnaires to elicit symptoms. A thorough ocular assessment is also performed to exclude any co-existent ocular conditions. A medical and mental health history should be sought due to associations with autoimmune disease, chronic pain syndromes, anxiety and depression. Management begins with communicating to the patient the nature of their condition. Ophthalmologists can prescribe topical therapies such as autologous serum eyedrops to optimise the ocular surface and promote neural regeneration. However, a multi-disciplinary treatment approach is often required, including mental health support, particularly when there are central mechanisms. General practitioners, pain specialists, neurologists and psychologists may be needed to assist with oral and behavioural therapies. Less data is available to support the safety and efficacy of adjuvant and surgical therapies and the long-term natural history remains to be determined. Hence clinical trials and registry studies are urgently needed to fill these data gaps with the aim to improve patient care.

Antimicrobial resistance in ocular infection: A review.

Antimicrobial resistance (AMR) is a global public health threat with significant impact on treatment outcomes. The World Health Organization's Global Action Plan on AMR recommended strengthening the evidence base through surveillance programs and research. Comprehensive, timely data on AMR for organisms isolated from ocular infections are needed to guide treatment decisions and inform researchers and microbiologists of emerging trends. This article aims to provide an update on the development of AMR in ocular organisms, AMR in bacterial ocular infections and on AMR stewardship programs globally. The most common ocular pathogens are Pseudomonas aeruginosa, Staphylococcus spp., Streptococcus pneumoniae, and Haemophilus influenzae in ocular infections. A variety of studies and a few surveillance programs worldwide have reported on AMR in these infections over time. Fluoroquinolone resistance has increased particularly in Asia and North America. For conjunctivitis, the ARMOR cumulative study in the USA reported a slight decrease in resistance to ciprofloxacin. For keratitis, resistance to methicillin has remained stable for S. aureus and CoNS, while resistance to ciprofloxacin has decreased for MRSA globally. Methicillin-resistance and multidrug resistance are also emerging, requiring ongoing monitoring. Antimicrobial stewardship (AMS) programmes have a critical role in reducing the threat of AMR and improving treatment outcomes. To be successful AMS must be informed by up-to-date AMR surveillance data. As a profession it is timely for ophthalmology to act to prevent AMR leading to greater visual loss through supporting surveillance programmes and establishing AMS.

Globe trauma associated with falls at Australian tertiary centres.

OBJECTIVE: Falls frequently cause globe and adnexal trauma, particularly in the elderly. The morbidity decreases confidence, independence and quality of life. We aimed to improve the understanding of fall-related globe and adnexal trauma and the involvement of ophthalmology at two tertiary trauma centres. METHODS: A retrospective medical record review was conducted at Royal North Shore Hospital and Royal Prince Alfred Hospital of patients admitted with fall-related globe and/or adnexal trauma between January 2015 and December 2019. International Classification of Disease Tenth Revision codes were used to identify patients for inclusion. Medical records were reviewed to extract data on demographics, trauma, ocular examination and referrals to ophthalmology. RESULTS: From January 2015 to December 2019, 346 patients, 186 were female (54%) and median age 76 years (interquartile range 24 years), were admitted to Royal North Shore Hospital and Royal Prince Alfred Hospital with fall-related globe and/or adnexal trauma. One hundred and twenty-five (36%) suffered globe trauma with 48 (14%) classified as severe. Patients over 65 years old had at least three risk factors contributing to falls. Alcohol and illicit substances were involved in 20% of falls and occurred predominantly in younger populations. There were significantly more patients with globe trauma if orbital/mid-facial fractures were present (55% vs 36%, P < 0.001). CONCLUSION: Fall-related globe and adnexal trauma were more common in the elderly. Alcohol and illicit substances have a role in falls in younger populations. Thorough ocular assessment is required especially in mid-facial/orbital trauma to exclude globe trauma. Further, research is required to determine the effect of fall prevention strategies in preventing globe trauma.

Comparison of standard versus accelerated corneal collagen cross-linking for keratoconus: 5-year outcomes from the Save Sight Keratoconus Registry.

OBJECTIVE: To compare long-term effectiveness of Standard (UV intensity: 3 mW/cm2, duration: 30 min) vs Accelerated (UV intensity: 9 mW/cm2, duration: 10 min) corneal cross-linking (CXL) for stabilising keratoconus. METHODS: Data for this observational study were captured through a web-based registry system from the routine clinical practice (15 sites across Australia, New Zealand and Italy). The outcomes were compared using mixed-effects regression models. A total of 100 eyes (75 patients) who had standard CXL and 76 eyes (66 patients) who had accelerated CXL, with a follow-up visit at five-year post-CXL were included. RESULTS: Both CXL protocols were effective and safe in stabilising keratoconus and improving outcomes. The adjusted mean changes (95% CI) in outcomes were better in standard CXL than in accelerated CXL [visual acuity gain, 10.2 (7.9-12.5) vs 4.9 (1.6-8.2) logMAR letters; pinhole visual acuity 5.7 (3.5-7.8) vs 0.2 (-2.2 to 2.5) logMAR letters; Kmax -1.8 (-4.3 to 0.6) vs 1.2 (-1.5 to 3.9)D; K2 -0.9 (-2.2 to 0.3) vs 0.1 (-1.3 to 1.6)D; MCT -3.0 (-13.7 to 7.7) vs -11.8 (-23.9 to 0.4) µm (p values for visual acuity, pinhole visual acuity, Kmax: <0.05; for K2 and MCT: >0.05)]. The frequency of adverse events at the 5-year follow-up visit was low in both groups [standard, 5 (5%; haze 3; scarring 1, epithelial defect 1) and accelerated 3 (3.9%; haze 2, scarring 1)]. CONCLUSIONS: Both standard and accelerated CXL were safe and effective procedures for stabilising keratoconus in the long term. The standard CXL resulted in greater improvements in visual acuity and keratometry.

The Risk of Sympathetic Ophthalmia Associated with Open-Globe Injury Management Strategies: A Meta-analysis.

TOPIC: Sympathetic ophthalmia (SO) is a sight-threatening granulomatous panuveitis caused by a sensitizing event. Primary enucleation or primary evisceration, versus primary repair, as a risk management strategy after open-globe injury (OGI) remains controversial. CLINICAL RELEVANCE: This systematic review was conducted to report the incidence of SO after primary repair compared with that of after primary enucleation or primary evisceration. This enabled the reporting of an estimated number needed to treat. METHODS: Five journal databases were searched. This review was registered with International Prospective Register of Systematic Reviews (identifier, CRD42021262616). Searches were carried out on June 29, 2021, and were updated on December 10, 2022. Prospective or retrospective studies that reported outcomes (including SO or lack of SO) in a patient population who underwent either primary repair and primary enucleation or primary evisceration were included. A systematic review and meta-analysis were carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Random effects modelling was used to estimate pooled SO rates and absolute risk reduction (ARR). RESULTS: Eight studies reporting SO as an outcome were included in total. The included studies contained 7500 patients and 7635 OGIs. In total, 7620 OGIs met the criteria for inclusion in this analysis; SO developed in 21 patients with OGI. When all included studies were pooled, the estimated SO rate was 0.12% (95% confidence interval [CI], 0.00%-0.25%) after OGI. Of 779 patients who underwent primary enucleation or primary evisceration, no SO cases were reported, resulting in a pooled SO estimate of 0.05% (95% CI, 0.00%-0.21%). For primary repair, the pooled estimate of SO rate was 0.15% (95% CI, 0.00%-0.33%). The ARR using a random effects model was -0.0010 (in favour of eye removal; 95% CI, -0.0031 [in favor of eye removal] to 0.0011 [in favor of primary repair]). Grading of Recommendations, Assessment, Development, and Evaluations analysis highlighted a low certainty of evidence because the included studies were observational, and a risk of bias resulted from missing data. DISCUSSION: Based on the available data, no evidence exists that primary enucleation or primary evisceration reduce the risk of secondary SO. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Burn related globe and adnexal trauma at trauma centres.

INTRODUCTION: Prompt management of burn-related globe trauma can prevent long term complications. Delays in diagnosis may occur when globe trauma is associated with life-threatening injuries. We aimed to improve the understanding of the epidemiology, acute assessment and management of burns-related globe and adnexal trauma admitted to two trauma centres in Sydney, Australia. METHOD: Admitted patients with burns-related globe and/or adnexal trauma were retrospectively reviewed at Royal North Shore Hospital (RNSH) and Royal Prince Alfred Hospital (RPAH) between January 2015 and December 2019. The International Classification of Disease, Tenth Revision codes was used to search and identify patients. Medical records were reviewed to extract data on demographics, injuries, ocular examination and ophthalmology involvement. RESULTS: Over the 5-years, 101 patients with globe and/or adnexal burns-related trauma were admitted to RNSH or RPAH. Median age was 37years. Most patients were male (76%) and were injured while at home or work (74%). Patients with chemical exposure were more likely to have globe trauma (100% vs 72%, p < 0.001) and severe globe trauma (54% vs 32%, p = 0.028). On initial review by emergency staff, 14 patients were not referred to ophthalmology, of these there were 2 patients where the diagnosis was delayed. CONCLUSION: Globe trauma is common in patients with chemical exposure. Thorough ocular assessment within the acute setting is vital to diagnose globe trauma. We investigated hospitals with specialised burn staff, further research is required to understand the management of globe trauma in hospitals without such resources. SYNOPSIS: Chemicals in household-products can cause severe globe trauma. Globe trauma can occur alongside large burns leading to delay in its diagnosis and management. Ophthalmology can assist in the early diagnosis and management of globe trauma.

Updates in Diagnostic Imaging for Infectious Keratitis: A Review.

Infectious keratitis (IK) is among the top five leading causes of blindness globally. Early diagnosis is needed to guide appropriate therapy to avoid complications such as vision impairment and blindness. Slit lamp microscopy and culture of corneal scrapes are key to diagnosing IK. Slit lamp photography was transformed when digital cameras and smartphones were invented. The digital camera or smartphone camera sensor's resolution, the resolution of the slit lamp and the focal length of the smartphone camera system are key to a high-quality slit lamp image. Alternative diagnostic tools include imaging, such as optical coherence tomography (OCT) and in vivo confocal microscopy (IVCM). OCT's advantage is its ability to accurately determine the depth and extent of the corneal ulceration, infiltrates and haze, therefore characterizing the severity and progression of the infection. However, OCT is not a preferred choice in the diagnostic tool package for infectious keratitis. Rather, IVCM is a great aid in the diagnosis of fungal and Acanthamoeba keratitis with overall sensitivities of 66-74% and 80-100% and specificity of 78-100% and 84-100%, respectively. Recently, deep learning (DL) models have been shown to be promising aids for the diagnosis of IK via image recognition. Most of the studies that have developed DL models to diagnose the different types of IK have utilised slit lamp photographs. Some studies have used extremely efficient single convolutional neural network algorithms to train their models, and others used ensemble approaches with variable results. Limitations of DL models include the need for large image datasets to train the models, the difficulty in finding special features of the different types of IK, the imbalance of training models, the lack of image protocols and misclassification bias, which need to be overcome to apply these models into real-world settings. Newer artificial intelligence technology that generates synthetic data, such as generative adversarial networks, may assist in overcoming some of these limitations of CNN models.

Pentadecanoic Acid (C15:0), an Essential Fatty Acid, Shares Clinically Relevant Cell-Based Activities with Leading Longevity-Enhancing Compounds.

Pentadecanoic acid (C15:0) is an essential odd-chain saturated fatty acid with broad activities relevant to protecting cardiometabolic, immune, and liver health. C15:0 activates AMPK and inhibits mTOR, both of which are core components of the human longevity pathway. To assess the potential for C15:0 to enhance processes associated with longevity and healthspan, we used human cell-based molecular phenotyping assays to compare C15:0 with three longevity-enhancing candidates: acarbose, metformin, and rapamycin. C15:0 (n = 36 activities in 10 of 12 cell systems) and rapamycin (n = 32 activities in 12 of 12 systems) had the most clinically relevant, dose-dependent activities. At their optimal doses, C15:0 (17 µM) and rapamycin (9 µM) shared 24 activities across 10 cell systems, including anti-inflammatory (e.g., lowered MCP-1, TNFα, IL-10, IL-17A/F), antifibrotic, and anticancer activities, which are further supported by previously published in vitro and in vivo studies. Paired with prior demonstrated abilities for C15:0 to target longevity pathways, hallmarks of aging, aging rate biomarkers, and core components of type 2 diabetes, heart disease, cancer, and nonalcoholic fatty liver disease, our results support C15:0 as an essential nutrient with activities equivalent to, or surpassing, leading longevity-enhancing candidate compounds.

Epithelium-on versus epithelium-off corneal collagen crosslinking for keratoconus: a systematic review and meta-analysis.

PURPOSE: Corneal collagen crosslinking (CXL) is the primary treatment for progressive keratoconus which has a significant impact on vision and quality of life. Our study aimed to compare the efficacy and safety of epithelium-on versus epithelium-off CXL to treat keratoconus. METHODS: We searched PubMed, Medline, Embase, Web of Science, and Scopus databases. We included studies that compared standard epithelium-off with epithelium-on CXL. The primary outcome measures were changes in corrected distance visual acuity (CDVA) and maximum keratometry (Kmax), and the secondary outcomes were uncorrected distance visual acuity (UDVA), central corneal thickness (CCT), and adverse events. A meta-analysis was performed on the primary and secondary outcomes based on the weighted mean differences between baseline to 12-month follow-up. RESULTS: The search retrieved 887 publications with 27 included in the systematic review. A total of 1622 eyes (1399 patients; age 25.51 ± 4.02 years) were included in comparisons of epithelium-off to epithelium-on CXL in keratoconus. Epithelium-off CXL treated 800 eyes and epithelium-on CXL for 822 eyes. At 12-month follow-up, CDVA and Kmax showed no significant difference between the epithelium-off and epithelium-on CXL. The secondary outcomes showed that UDVA was better in epithelium-off CXL (- 0.11D, 95% CI - 0.12, - 0.1; p < 0.001) and there was more thinning in CCT in epithelium-off CXL (- 3.23 µm, 95% CI - 4.64, - 1.81; p <0.001). CONCLUSION: Epithelium-off and epithelium-on CXL were both effective to treat progressive keratoconus. Further research is needed to compare the long-term outcomes and safety of both CXL protocols for adaptation into clinical practice.

Evaluation of ocular neuropathic pain.

AIM: To identify and assess the quality of current validated questionnaires that could be used to evaluate ocular neuropathic pain and its associated aetiologies. METHODS: A literature search was performed on MEDLINE, PubMed, EMBASE, PsycINFO and The Cochrane Library. Articles evaluating questionnaires for ocular neuropathic pain and its associated aetiologies were included. Data on psychometric properties, validity, and reliability of the questionnaires was extracted and analysed using a set of quality criteria. Clinical and demographical associations with ocular neuropathic pain were also reviewed. RESULTS: The search generated 1738 results with 61 publications meeting the inclusion criteria. The 61 publications covered 28 questionnaires including 3 ocular pain, 12 dry eye disease, 2 blepharitis, 2 refractive surgery, 3 contact lens wear, 3 Sjogren's Syndrome, and 3 that were non-disease-specific. Only 57 publications provided enough data on psychometric properties and validity of the questionnaire to be included for quality assessment. The Contact Lens Discomfort Index (CLDI) had the highest rated psychometric properties, whereas the English version of the Ocular Comfort Index (OCI) provided the most data on psychometric properties (9 out of 10 criteria). Most ocular pain and disease-specific questionnaires contained appropriate items to assess ocular pain in specific populations. However, non-disease-specific ophthalmic questionnaires demonstrated poor reliability and validity when evaluating ocular pain. CONCLUSION: Ocular pain questionnaires can potentially diagnose ocular neuropathic pain. Disease-specific questionnaires were limited to their target populations, and non-disease-specific ophthalmic questionnaires were unreliable. Further studies are required to determine the most appropriate questionnaire to evaluate ocular neuropathic pain.

Efficacy and safety of AZR-MD-001 selenium sulfide ophthalmic ointment in adults with meibomian gland dysfunction: A vehicle-controlled, randomized clinical trial.

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.

Rosacea Meibomian Gland Dysfunction Posterior Blepharitis May Be a Marker for Earlier Associated Dyslipidaemia and Inflammation Detection and Treatment with Statins.

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.

The Use of Preoperative Prophylactic Systemic Antibiotics for the Prevention of Endopthalmitis in Open Globe Injuries: A Meta-Analysis.

TOPIC: This study reports the effect of systemic prophylactic antibiotics (and their route) on the risk of endophthalmitis after open globe injury (OGI). CLINICAL RELEVANCE: Endophthalmitis is a major complication of OGI; it can lead to rapid sight loss in the affected eye. The administration of systemic antibiotic prophylaxis is common practice in some health care systems, although there is no consensus on their use. METHODS: PubMed, CENTRAL, Web of Science, CINAHL, and Embase were searched. This was completed July 6, 2021 and updated December 10, 2022. We included randomized and nonrandomized prospective studies which reported the rate of post-OGI endophthalmitis when systemic preoperative antibiotic prophylaxis (via the oral or IV route) was given. The Cochrane Risk of Bias tool and ROBINS-I tool were used for assessing the risk of bias. Where meta-analysis was performed, results were reported as an odds ratio. PROSPERO registration: CRD42021271271. RESULTS: Three studies were included. One prospective observational study compared outcomes of patients who had received systemic or no systemic preoperative antibiotics. The endophthalmitis rates reported were 3.75% and 4.91% in the systemic and no systemic preoperative antibiotics groups, a nonsignificant difference (P = 0.68). Two randomized controlled trials were included (1555 patients). The rates of endophthalmitis were 17 events in 751 patients (2.26%) and 17 events in 804 patients (2.11%) in the oral antibiotics and IV (± oral) antibiotics groups, respectively. Meta-analysis demonstrated no significant differences between groups (odds ratio, 1.07; 95% confidence interval, 0.54-2.12). CONCLUSIONS: The incidences of endophthalmitis after OGI were low with and without systemic antibiotic prophylaxis, although high-risk cases were excluded in the included studies. When antibiotic prophylaxis is considered, there is moderate evidence that oral antibiotic administration is noninferior to IV. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Genetic predisposition to ocular surface disorders and opportunities for gene-based therapies.

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.

Mental Health Impact of Keratoconus: A Systematic Review.

PURPOSE: The aim of this study was to investigate the impact of keratoconus on the mental health and emotional well-being of affected patients. METHODS: A literature search was conducted according to the PRISMA guidelines. Databases searched included MEDLINE, PubMed, EMBASE, Scopus, Web of Science, Cochrane, and PsycINFO. Articles were included if they were a primary study that investigated mental health or emotional quality-of-life outcomes in patients with keratoconus. RESULTS: Thirty-one articles met inclusion criteria of a total yield of 444. Most studies reported keratoconus to have a negative effect on mental health or emotional well-being. Worsening mental health scores correlated with lower visual acuity (VA) in the better eye, lower VA in the worse eye, increasing ocular asymmetry, and worsening disease severity. Mental health impacts were often reported to be disproportionate to that of the effects on VA. Over time mental health outcomes improved, suggesting stabilization of disease and patient acceptance. CONCLUSIONS: Patients with keratoconus may suffer detriments to mental health despite having relatively good VA. Understanding and acceptance of their disease may assist in assuaging mental health concerns. Further work may be needed to investigate whether benefit exists in routine mental health screening of patients with keratoconus.

Mucous membrane grafting for cicatricial entropion repair: review of surgical techniques and outcomes.

Mucous membrane graft (MMG) is used for moderate-to-severe cicatricial entropion repair either in primary or recurrent cases. We conducted a review to comprehensively summarize the various surgical techniques, outcomes, and complications of using MMG for cicatricial entropion. Though the comparison between different techniques is limited by multiple factors like small numbers of cicatricial entgropion patients, variable severity and success criteria across studies, and different underlying cicatricial entropion etiologies, the author has brought forth the nuances of the use of MMG for cicatricial entropion repair along with its outcomes and complications. MMG use in moderate-to-severe cicatricial entropion gives favourable outcomes. The shortened tarsoconjunctiva is lengthened using MMG, which is used either with terminal tarsal rotation or anterior lamellar recession (ALR) or tarsotomy alone. Non-trachomatous entropion has poor outcomes compared to trachomatous entropion. The most common source of MMG is labial or buccal mucosa and the exact size of MMG harvested is variable according to the defect, and very few prefer oversizing the graft by 10-30%. The outcomes of ALR+MMG appear similar to tarsal rotation and MMG for severe cicatricial entropion. The recurrences of trichiasis or entropion can occur for up to one year after surgery, irrespective of the technique used. Factors affecting the outcomes of cicatricial entropion repair are not well known. There is a non-uniformity in data reporting across literature; hence, future studies with details on severity of entropion, ocular surface changes, forniceal depth and ocular surface inflammation, and the degree of dry eye disease would be informative.