Appropriateness of Questionnaires for the Diagnosis and Monitoring Treatment of Dry Eye Disease.

Objectives: If questionnaires contributing to the diagnosis of dry eye disease are to be recommended as alternatives to existing questionnaires, they must be comparable, with similar repeatability and treatment sensitivity. Comparability was thus examined for three common dry eye questionnaires along with identifying the individual questions that most strongly predicted overall scores. Methods: Anonymised data (n = 329) collected via the Ocular Surface Disease Index (OSDI), 5-item Dry Eye Questionnaire (DEQ-5) and Symptom Assessment in Dry Eye (SANDE) questionnaires (including responses to individual questions) from consenting patients were drawn from real-world dry eye clinics/registries in the United Kingdom, Australia and New Zealand; at follow-up, normalised changes were evaluated in 54 of these patients. Treatment data were also analysed from a 6-month, randomised controlled trial assessing artificial tear supplement treatments with 43 responders and 13 non-responders to treatment identified. The questions extracted from the OSDI which form the abbreviated 6-item OSDI were also analysed. Results: The agreement between the questionnaires ranged from r = 0.577 to 0.754 (all p < 0.001). For the OSDI, three questions accounted for 89.1% of the variability in the total score. The correlation between the OSDI and OSDI-6 was r = 0.939, p < 0.001. For the DEQ-5, two questions accounted for 88.5% of the variance in the total score. Normalised treatment changes were also only moderately correlated between the questionnaires (r = 0.441 to 0.595, p < 0.01). For non-responders, variability was 7.4% with both OSDI and OSDI-6, 9.7% with DEQ-5, 12.1% with SANDE-frequency and 11.9% with SANDE-severity scale. For responders, improvement with drops was detected with a 19.1% change in OSDI, 20.2% in OSDI-6, 20.9% in DEQ-5, and 27.5%/23.6% in SANDE-frequency/severity scales. Conclusions: Existing commonly used dry eye questionnaire scores do not show high levels of correlation. The OSDI was the least variable of the questionnaires and while displaying a slightly lower treatment effect than either the DEQ or SANDE, it was more sensitive to detection of a treatment effect. The quicker-to-complete OSDI-6 exhibited essentially the same outcome as the OSDI, with similar variability and treatment sensitivity.

The incidence of falls after first and second eye cataract surgery: a longitudinal cohort study.

OBJECTIVE: To compare fall incidence, and visual acuity and refractive status, before surgery and after first and second eye cataract surgery. DESIGN, SETTING: Prospective observational study in eight tertiary referral ophthalmology clinics in public hospitals in Sydney, Melbourne, and Perth. PARTICIPANTS: People aged 65 years or more referred for bilateral age-related cataract surgery during 2013-16, followed for maximum of 24 months after study entry or until six months after second eye surgery, whichever was shorter. MAIN OUTCOME MEASURES: Primary outcome: age- and sex-adjusted incidence of falls. SECONDARY OUTCOMES: visual acuity and refractive error. RESULTS: The mean age of the 409 included participants was 75.4 years (SD, 5.4 years); 220 were women (54%). Age- and sex-adjusted fall incidence prior to surgery was 1.17 (95% CI, 0.95-1.43) per year, 0.81 (95% CI, 0.63-1.04) per year after first eye surgery, and 0.41 (95% CI, 0.29-0.57) per year after second eye surgery. For the 118 participants who underwent second eye surgery and participated in all follow-up visits, age- and sex-adjusted incidence before (0.80 [95% CI, 0.55-1.15] falls per year) and after first eye surgery (0.81 [95% CI, 0.57-1.15] falls per year) was similar, but was lower after second eye surgery (0.32 [95% CI 0.21-0.50] falls per year). Mean habitual binocular visual acuity (logMAR) was 0.32 (SD, 0.21) before surgery, 0.15 (SD, 0.17) after first eye surgery, and 0.07 (SD, 0.15) after second eye surgery. CONCLUSIONS: First eye surgery substantially improves vision in older people with cataract, but second eye surgery is required to minimise fall incidence. Timely cataract surgery for both eyes not only optimises vision in older people with cataract, but also reduces their risk of injury from falls.

Association study of single nucleotide polymorphisms in IL-10 and IL-17 genes with the severity of microbial keratitis.

PURPOSE: Exploratory analysis to assess the association of single nucleotide polymorphisms (SNPs) in the interleukin (IL) 10 and IL-17 genes with severity of contact lens keratitis. METHODS: This was a retrospective case control study of 88 contact lens keratitis cases (25 severe) and 185 healthy contact lens wearers recruited from studies conducted at Moorfields Eye Hospital and in Australia-wide during 2003-2005. Buccal swab samples were collected on Whatman FTA cards and mailed by post for DNA extraction and SNP genotyping. IL-10 (rs1800871; rs1800896; rs1800872) and IL-17 (rs1800871; rs1800896; rs1800872) SNPs were screened by pyrosequencing. Genetic association analyses were performed via Cochran-Armitage trend tests and logistic regression models using PLINK software. RESULTS: None of the SNPs tested showed evidence of association with severity of contact lens keratitis at P <  0.05. Nevertheless, minor allele G in SNP rs2397084 of the IL-17F gene was associated with increased risk of severe MK, with OR=2.1 (95% CI=0.9-4.8, P = 0.066). CONCLUSION: Our study cannot exclude with confidence that genetic variation in the IL-17 F proinflammatory cytokine is associated with more severe outcomes of MK. However, there is general body of information that the IL-17 pathway is important in the mechanisms of MK. Studies with larger power and the expanded array of laboratory tools will elucidate the exact role of IL-17 in MK.

The Asia Cornea Society Infectious Keratitis Study: A Prospective Multicenter Study of Infectious Keratitis in Asia.

PURPOSE: To survey the demographics, risk factors, microbiology, and outcomes for infectious keratitis in Asia. DESIGN: Prospective, nonrandomized clinical study. METHODS: Thirteen study centers and 30 sub-centers recruited consecutive subjects over 12-18 months, and performed standardized data collection. A microbiological protocol standardized the processing and reporting of all isolates. Treatment of the infectious keratitis was decided by the managing ophthalmologist. Subjects were observed for up to 6 months. Main outcome measures were final visual acuity and the need for surgery during infection. RESULTS: A total of 6626 eyes of 6563 subjects were studied. The majority of subjects were male (n = 3992). Trauma (n = 2279, 34.7%) and contact lens wear (n = 704, 10.7%) were the commonest risk factors. Overall, bacterial keratitis was diagnosed in 2521 eyes (38.0%) and fungal keratitis in 2166 eyes (32.7%). Of the 2831 microorganisms isolated, the most common were Fusarium species (n = 518, 18.3%), Pseudomonas aeruginosa (n = 302, 10.7%), and Aspergillus flavus (n = 236, 8.3%). Cornea transplantation was performed in 628 eyes to manage ongoing infection, but 289 grafts (46%) had failed by the end of the study. Moderate visual impairment (Snellen vision less than 20/60) was documented in 3478 eyes (53.6%). CONCLUSION: Demographic and risk factors for infection vary by country, but infections occur predominantly in male subjects and are frequently related to trauma. Overall, a similar percentage of bacterial and fungal infections were diagnosed in this study. Visual recovery after infectious keratitis is guarded, and corneal transplantation for active infection is associated with a high failure rate.

Patient perspectives of cataract surgery: protocol and baseline findings of a cohort study.

BACKGROUND: Patient-reported outcome measures (PROMs) are becoming increasingly recognised as a key component in assessing the relative effectiveness of cataract surgery. This manuscript presents the protocol methodology and baseline characteristics of a prospective cohort study investigating patient-centred predictors of cataract surgery outcomes. METHODS: Patients with bilateral cataract (aged ≥ 50 years) scheduled for their first eye cataract surgery were recruited at four public hospitals and three private ophthalmology clinics in Sydney, Australia. Participants underwent a comprehensive assessment of clinical measures of vision (for example, visual acuity, contrast sensitivity) and PROMs prior to first eye surgery and three months after first and second eye surgery. The PROMs of interest included health-related quality of life, visual disability and satisfaction with vision. RESULTS: The characteristics of the baseline cohort of 359 participants are reported in this manuscript. Enrolment occurred over a two-year period with the majority recruited from urban public hospitals (96 per cent, n = 345). Health-related quality of life was scored highly (80 out of 100). Self-reported visual disability was considered within normal ranges compared to cataract populations in other high-income countries (-0.94 logits). Three-quarters of participants (n = 263/351) were dissatisfied with their pre-operative vision. CONCLUSIONS: There is a complex and wide range of patient-centred experiences prior to first eye cataract surgery in the public hospital setting. Gaining further insight into the patient perspective may allow eye health professionals to more appropriately time surgery, better manage patient expectations and provide direction for future prioritisation initiatives of cataract wait lists. Companion papers will follow, detailing results of surgery in terms of PROMs.

Are cataract surgery referrals to public hospitals in Australia poorly targeted?

IMPORTANCE: Referral letters constitute the first step on the pathway to cataract surgery; however, little is known on how effective referral letters are in providing adequate information to triage patients and inform surgical prioritization. BACKGROUND: Benchmarking exercises are important to document referral processes and to identify areas where improvements can be made. DESIGN: Cross-sectional study with longitudinal follow-up conducted at two metropolitan public hospitals in New South Wales, Australia. PARTICIPANTS: A total of 400 sequential cataract referral letters. METHODS: An audit of cataract referral letters was performed and content benchmarked against international prioritization tools. Medical records were reviewed 1 year following referral. MAIN OUTCOME MEASURES: Referral quality and waiting times. RESULTS: Two-thirds of patients referred for cataract surgery were yet to have their initial hospital appointment in the year following referral (65%, 245/376). One half of referrals seen in clinic (49%, 64/113) were not listed for cataract surgery. Multivariate analysis revealed referral letter content was not indicative of surgical booking, with the major predictors being hospital-recorded visual acuity and grading of cataract (P < 0.0001). Referral content lacked sufficient detail to apply prioritization tools developed in other settings. CONCLUSION AND RELEVANCE: This audit highlights a disconnect between referral letter content and hospital assessment of patients. Current referrals to public hospitals are poorly targeted, with high numbers of referred patients not proceeding to surgery. Patients commonly waited over 1 year to have their ophthalmic assessment at these public hospital eye clinics, revealing lengthy 'wait-for-waits' as a barrier to care. Standardized referral templates may facilitate improvement of referral pathways and shorten waiting times.

A pilot study on corneal Langerhans cells in keratoconus.

PURPOSE: To report the density and morphology of cells that are analogous to corneal Langerhans cells and their associations in keratoconus. MATERIALS AND METHODS: This prospective cross-sectional study included a convenience sample of keratoconus subjects aged between 18-65 years. Corneal topography, assessment of ocular symptoms, tear variables, corneal sensitivity, in-vivo confocal microscopy were performed. The number of Langerhans cells were manually counted and averaged across three central corneal images. Cell morphology was graded on a 0-3 scale, where grade 3 indicates cells with long visible dendrites. Associations of Langerhans cells with other variables were evaluated using Spearman's correlation. RESULTS: Twenty-one keratoconus subjects with a mean age of 43±11 years were included. Eighty-one percent of them were males, 48% had mild keratoconus and 52% were contact lens wearers. Langerhans cells were present in the central cornea in 91% of subjects. Median cell density was 15 cells/mm2(IQR: 3-21). Cell morphology of grades 2 or 3 (with short or long dendrites) was seen in 71% of subjects. There was a significant association between Langerhans cell frequency and density with male gender (rho and p-values: -0.669, 0.001 and -0.441,0.045) and between Langerhans cell density and nerve fibre tortuosity (0.479,0.028). No significant association observed with age, contact lens wear or ocular symptoms. CONCLUSION: Langerhans cells were present in a significant number of subjects suggesting the possibility of inflammation in keratoconus. Based on the association of Langerhans cells with nerve parameters, we propose inflammation as the underlying cause for corneal nerve changes in keratoconus.

TFOS DEWS II Report Executive Summary.

This article presents an Executive Summary of the conclusions and recommendations of the 10-chapter TFOS DEWS II report. The entire TFOS DEWS II report was published in the July 2017 issue of The Ocular Surface. A downloadable version of the document and additional material, including videos of diagnostic and management techniques, are available on the TFOS website: www.TearFilm.org.

Differences in Tear Film Biochemistry of Symptomatic and Asymptomatic Lens Wearers.

SIGNIFICANCE: The concentration of selected proteins and inflammatory mediators in tears of symptomatic and asymptomatic contact lens wearers were quantified. The level of leukotriene B4 was higher in the symptomatic group. This may suggest that inflammation can be the cause of discomfort sensation at the end of day. PURPOSE: The present study aims to quantify the concentration of selected tear lipids and proteins in symptomatic and asymptomatic contact lens wearers. METHODS: Unstimulated evening tears were collected using glass capillary tubes from 45 healthy, adapted contact lens wearers. Twenty-two had self-described symptoms of dryness and discomfort with contact lenses and 23 were asymptomatic. Tear proteins were assayed using selected reaction monitoring mass spectrometry. Enzyme immunoassay kits were used to measure prostaglandins, leukotriene B4, and cysteinyl leukotrienes. Ocular comfort was rated on a scale of 1 to 100 at the time of tear collection. RESULTS: The average evening comfort level was above 70 for the asymptomatic (83.96 ± 9.51, mean ± SE) and equal or below 70 for the symptomatic group (57.28 ± 12.38) (P < .001). LTB4 was significantly higher in symptomatic than asymptomatic contact lens wearers (0.32 ± 0.06 ng/µL vs. 0.17 ± 0.04 ng/µL, respectively; P = .03). Lysozyme was slightly but not significantly lower in symptomatic subjects (symptomatic 0.58 ± 0.10 mg/mL vs. asymptomatic 1.73 ± 0.46 mg/mL; P = .10). The levels of lactoferrin, lipocalin 1, proline-rich 4, prolactin-induced protein, prostaglandins, and cysteinyl leukotrienes were unchanged (P > .1) between symptomatic and asymptomatic subjects. CONCLUSIONS: The LTB4 concentration was significantly higher in symptomatic contact lens wearers compared to the asymptomatic group, and this may partly mediate the discomfort response during lens wear in the symptomatic lens wearers. No other differences were found in the level of tear factors of interest between the two groups.

Infection control guidelines for optometrists 2016.

BACKGROUND: This paper provides an updated version of the paper: Infection control guidelines for optometrists 2007. METHODS: Information from peer-reviewed journal articles, guidelines from professional societies, and government health department and other websites and instructions from equipment manufacturers were considered in determining infection risk factors in optometric practice. They were used to revise the recommendations on disinfection, sterilisation and reprocessing procedures for instrumentation and other equipment used in optometric practice as well as personal infection control measures to be undertaken by staff. RESULTS AND CONCLUSIONS: Optometrists and optometric practice staff should adopt measures to minimise the risk of transmission of infection. These include appropriate hand-washing, staff vaccinations, single use instruments/equipment, appropriate disposal of waste, appropriate methods of reprocessing where items are reused, routine employment of standard infection control precautions and application of more rigorous procedures for individuals who are known to be infected or immuno-suppressed. Information provided to patients regarding infection control procedures in topical drug administration, contact lens wear and use of eye make-up are additional considerations for optometrists.

Pilot Study of Corneal Sensitivity and Its Association in Keratoconus.

PURPOSE: To evaluate corneal sensitivity and its association with other clinical parameters in keratoconus. METHODS: Twenty-four subjects with keratoconus aged between 18 and 65 years were recruited in this cross-sectional study. Ocular symptoms, corneal topography, tear variables such as tear osmolarity, volume and lower tear meniscus height, ocular surface staining, central sensitivity threshold (CST), and corneal subepithelial nerve mapping were obtained. Association between central CST and other clinical variables was examined using the Spearman correlation coefficient. Partial correlation was performed to control for effects of confounding factors. RESULTS: Data from the most severe eye of each subject were included in analyses. Based on the maximum simulated keratometry (Kmax) reading, subjects were graded as having mild (N = 11; K max ≤ 52 D) or severe (N = 13; K max > 52 D) keratoconus. Central corneal sensitivity was lower (ie, increased CST) in the severe keratoconus group compared with that in the mild keratoconus group (median, interquartile range: 1.09; 0.60-19.66 vs. 0.51; 0.39-1.51 g/mm, P = 0.035). In bivariate correlations, reduced corneal sensitivity in keratoconus was associated with age (ρ = 0.42, P = 0.040), disease duration (ρ = 0.49, P = 0.015) and severity (ρ = 0.44; P = 0.032), lower central nerve fiber density (ρ = -0.68, P = 0.014), contact lens wear (ρ = 0.44; P = 0.025), and contact lens tolerance (ρ = 0.46; P = 0.033). After adjusting for contact lens wear, reduced corneal sensitivity was negatively associated with ocular symptoms (ρ = -0.426, P = 0.048) and pain sensitivity (ρ = -0.423, P = 0.045) and positively associated with corneal staining (ρ = 0.52, P = 0.011). CONCLUSIONS: Altered corneal sensitivity in keratoconus affected ocular symptoms and ocular surface health, which may have significant impact on the success of management options for keratoconus.

Outcome of Keratoconus Management: Review of the Past 20 Years' Contemporary Treatment Modalities.

OBJECTIVES: To describe the past 20 years' contemporary management modalities for keratoconus (KC) and their outcomes and failures and to propose recommendations in reporting their outcomes. METHODS: A systematic review of the literature on KC management options for the last 20 years was performed. Original articles that reported the outcome of any form of KC management other than full-thickness or lamellar corneal graft were reviewed to collect information on their outcomes and complications and the level of scientific evidence of the study. RESULTS: A total of 1,147 articles retrieved and of those, 241 satisfied the inclusion criteria, and 41.1% of them were prospective case series. The higher level of evidence studies, that is, randomized controlled trials (RCTs), were limited to only one intervention, that is, corneal collagen cross-linking (CXL). However, the quality of most RCTs was limited because of performance and detection bias. Contact lenses (CLs) remain the mainstream of KC management and were associated with reversible and non-sight-threatening complications. Surgical options such as intracorneal segment implantation and phakic intraocular lens are considered in the visual rehabilitation of CL intolerants, and CXL is the only available option to stop or delay the disease progression. Generally, these surgical procedures are associated with transient inflammatory events and permanent sequelae. CONCLUSIONS: The published studies on KC management options varied significantly with respect to the study population, age of participants, severity of KC, clinical outcome measurements, and follow-up period. High-quality longer follow-up RCTs are required to evaluate the long-term effects of KC interventions.

Application of clinical techniques relevant for glaucoma assessment by optometrists: concordance with guidelines.

PURPOSE: Guidelines for the screening, prognosis, diagnosis, management and prevention of glaucoma were released by the Australian National Health and Medical Research Council in 2010. Comparable guidance has been made available by respective bodies in the USA and UK at a similar time. Key to successful translation of guidelines into clinical practice includes clinicians having the necessary skills to perform required tests. Optometrists in Australia and New Zealand were invited to participate in an online survey exploring these aspects. The results provide insights for improving glaucoma diagnosis and management by optometric primary eye care practitioners. METHODS: An online questionnaire was developed to investigate glaucoma assessment of optometrists as a function of demographic details, educational background and experience. Key points to ascertain compliance with current guidelines were the availability of equipment, procedural confidence in techniques, and preferences in visual field tests. Chi square statistics was employed to support similarity to national averages and highlight differences between the two countries. Multivariate linear regression analysis identified variables significantly associated with individual tests being available to optometrists and their confidence in applying them. RESULTS: Thirteen per cent of all Australian and 36% of the New Zealand optometrists responded to the survey in 2013, which reflected the demographics/geography of the practising populations. Techniques considered essential or preferred for glaucoma assessment were widely available in both countries with the exception of gonioscopy and pachymetry. After correcting for availability, regression models highlighted therapeutic endorsement and knowledge of glaucoma guidelines as the main variables to maintain high diagnostic confidence. Correlations to number of years in optometric practice mirrored a changed emphasis in teaching and technology over the past 10-15 years. CONCLUSIONS: Australian and New Zealand optometrists were well equipped to perform glaucoma assessments with the possible exception of gonioscopy. Advanced imaging modalities were not yet fully integrated into optometric practice, although optical coherence tomography has shown use by 23-32% of optometrists. A marked increase in use, availability and procedural confidence of gonioscopy and other techniques with therapeutically endorsed optometrists demonstrates the advantage and importance of additional training.

Method development for quantification of five tear proteins using selected reaction monitoring (SRM) mass spectrometry.

PURPOSE: To establish the use of selected reaction monitoring (SRM) mass spectrometry for quantification of tear proteins. METHODS: Tear samples were collected on multiple occasions (7-10 days) from healthy subjects with contact lens wear (CL = 3) and without contact lens wear (NCL = 4). Tear proteins were denatured using 8M urea, reduced with iodoacetamide, precipitated by acetone, and digested using trypsin. Internal standards were included by adding isotopically-labelled standards of known concentrations to the samples. Lactoferrin, lysozyme, prolactin-induced protein, lipocalin 1, and proline-rich protein 4 were quantified using liquid chromatography-triple quadruple mass spectrometry in conjunction with selected reaction monitoring. RESULTS: The limits of quantification for the selected peptides were below 50 pg/µL. The recovery of peptides from spiked digested tears was greater than or equal to 56% and the coefficient of variation values were less than or equal to 16%. The concentration of lactoferrin (1.20 ± 0.77 µg/µL), lysozyme (2.11 ± 1.50 µg/µL), and lipocalin-1 (1.75 ± 0.99 µg/µL) were consistent with previous ELISA studies. Tear levels of prolactin-induced protein (0.09 ± 0.06 µg/µL) and proline-rich 4 (0.80 ± 0.50 µg/µL) are reported here for the first time. CONCLUSIONS: The SRM method can be used for simultaneous detection and quantification of selected proteins in low volumes of human tear samples (2.5 µL per sample) without prior purification of each protein component or need for antibodies.

Clinical outcomes of keratitis.

OBJECTION: To analyse the patient, clinical and microbiological variables associated with poor outcomes from keratitis in patients presenting to a major public hospital in Australia. METHODS: A retrospective audit of the records of all patients who had a corneal scraping in 5 years at Princess Alexandra Hospital (Brisbane, Australia) was carried out. The outcome of a patient's episode of keratitis was classified as poor if they had final visual acuity of 6/60 or worse; had vision loss during treatment; or a complication of keratitis; or needed surgical intervention. RESULTS: A final outcome was established in 207 cases during the 5-year period. Final vision of 6/12 or better was found in 48% (100) of cases while a poor outcome was seen in 28% (58). Linear regression showed poor outcomes were directly associated with age (P < 0.001) and disease severity (P < 0.001). Univariate analysis indicated that poor outcomes were more likely in patients who had had prior ocular surgery (P = 0.005) or ocular surface disease (P = 0.01) and were also associated with presenting visual acuity of worse than 6/60 (P < 0.001) and isolation of Streptococcus pneumoniae (P = 0.002). While patients with traumatic keratitis, contact lens-related keratitis or negative corneal cultures (P = 0.009) were more likely to have good outcomes. Multivariate analysis showed that the relative risk of a patient having a poor outcome was 4.3x (CI 2.0-9.5) if they had severe keratitis, 4.1x (CI 1.8-9.5) if they had keratitis related to ocular surface disease and 3.8x (CI 1.8-8.3) if they were over 50 years old. CONCLUSIONS: An outcome of poor vision, vision loss during treatment, surgical intervention or complication of keratitis is more likely in patients with severe keratitis, keratitis related to prior ocular surface disease or older age.