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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Five-year corneal cross-linking outcomes: A Save Sight Keratoconus Registry Study.

BACKGROUND: We aimed to determine the long-term outcomes of epithelium-off cross-linking (CXL) in keratoconus patients. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Presumed Microbial Keratitis Cases Resulting in Evisceration and Enucleation in Sydney, Australia.

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.

Efficacy and Safety of Standard Corneal Cross-Linking Procedures Performed With Short Versus Standard Riboflavin Induction: A Save Sight Keratoconus Registry Study.

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.

Patient-Reported Outcomes in Keratoconus: A Save Sight Keratoconus Registry Study.

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.

Clinical Registries in Dry Eye Disease: A Systematic Review.

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.