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Objectives To assess the quality of diabetic eye disease clinical practice guidelines. Study design and setting A systematic search of diabetic eye disease guidelines was conducted on six online databases and guideline repositories. Four reviewers independently rated quality using the Appraisal of Guidelines, Research, and Evaluation (AGREE II) instrument. Aggregate scores (%) for six domains and overall quality assessment were calculated. A “good quality” guideline was one with ≥60% score for “rigor of development” and in at least two other domains. Results Eighteen guidelines met the inclusion criteria, of which 13 were evidence-based guidelines (involved systematic search and grading of evidence). The median scores (interquartile range (IQR)) for “scope and purpose,” “stakeholder involvement,” “rigor of development,” “clarity of presentation,” “applicability” and “editorial independence” were 73.6% (54.2%–80.6%), 48.6% (29.2%–71.5%), 60.2% (30.9%–78.1%), 86.6% (76.7%–94.4%), 28.6% (18.0%–37.8%) and 60.2% (30.9%–78.1%), respectively. The median overall score (out of 7) of all guidelines was 5.1 (IQR: 3.7–5.8). Evidence-based guidelines scored significantly higher compared to expert-consensus guidelines. Half (n = 9) of the guidelines (all evidence-based) were of “good quality.” Conclusion A wide variation in methodological quality exists among diabetic eyecare guidelines, with nine demonstrating “good quality.” Future iterations of guidelines could improve by appropriately engaging stakeholders, following a rigorous development process, including support for application in clinical practice and ensuring editorial transparency.

Significance Assessment of treatment efficacy via comparison with a target IOP is fundamental in monitoring patients with open-angle glaucoma and ocular hypertension. This article highlights that diurnal IOP fluctuations obtained using self-tonometry may more accurately reflect IOP responses to therapy. Purpose This study aimed to investigate fluctuations in diurnal IOP measurements in patients with open-angle glaucoma and ocular hypertension treated with latanoprost 0.005% and timolol 0.25%. Methods In this crossover treatment trial, 14 participants performed self-tonometry with iCare HOME 4 times daily for (1) 1 week using latanoprost, (2) 4 weeks using no medications, and (3) 2 weeks using timolol. Daily peak IOPs, IOP fluctuations, and mean IOPs from different treatments were compared on an individual basis. Treatment efficacy between medications was assessed by comparing mean percentage IOP reductions with latanoprost and timolol across participants. In addition, effects of age, years since commencing latanoprost, sex, and diagnosis were investigated, and peak IOP times were compared with assess impacts on diurnal profiles. Results Between individuals, IOP responses ranged from reductions in peak IOPs, IOP fluctuations, and mean IOPs on both medications to no change in any parameter and medication. IOP fluctuations showed greater mean percentage reductions than did peak and mean IOPs (χ2 = 16.51, P = .002). There were significant associations between years since commencing latanoprost and peak and mean IOP responses on timolol (r = 0.69, P = .007), and sex and relative reductions in IOP fluctuations on both medications (P = .03). There were no differences in peak IOP times between treatment conditions. Conclusions Despite variability in IOP responses to latanoprost and timolol, IOP fluctuation with self-tonometry was more consistent in evaluating target IOP, reflecting its importance in ascertaining true IOP response to topical therapies. These findings may impact clinical decision making based on target IOP criteria in patients on topical therapy.

Purpose A fundamental clinical skill is the recognition of artefacts within the outputs of advanced imaging modalities. However, current teaching programmes of healthcare practitioners are becoming increasingly challenged to provide practical exposure within an already crowded curriculum. This study evaluates the impact of a novel work-integrated teaching model on the confidence and competence of clinicians in the use of optical coherence tomography (OCT) and the recognition of its artefacts. The outcomes were then used to develop a model to predict performance and guide teaching strategies. Methods We prospectively evaluated a 6-week clinical placement for final year optometry students within a diagnostic eye clinic in 2018-2020. Participants completed a quiz on the identification of common OCT artefacts and rated their confidence levels on key areas of OCT application using a five-point Likert scale. Both were completed before (pre-rotation) and after (post-rotation) the placement. The cohort was divided into two groups; the first group was used to assess the impact of the placement and derive the prediction model for post-placement performance, which was then validated against the second group. Results A significant improvement in detecting OCT imaging artefacts was seen upon completion of the placement, which was greater in participants with lower entry level performance. Across all OCT artefact subtypes, there was an improvement in detecting segmentation error, delineation error and media opacities. A model predicting post-placement student performance was developed using entry level knowledge base as the key dependent variable. Self-rated confidence improved across all domains of OCT application but was not found to be a direct predictor of actual performance. Conclusions These results highlight the benefit of a work-integrated learning programme on both academic performance and confidence whilst identifying entry level knowledge base as the key variable predicting improvement. Tailored teaching incorporating entering knowledge is the best predictor of improvement during clinical placements. Integrating clinicians into a work-integrated setting with tailored teaching and comprehensive practical exposure can be an effective method for training future or current healthcare professionals.

PURPOSE The 2019 American Optometric Association (AOA) clinical practice guideline intends to assist optometrists in providing evidence-based eye care for people with diabetes. This technical report evaluated the methodological and reporting quality of the guideline. METHODS Four independent reviewers appraised the 2014 and 2019 versions of the AOA's guideline using the AGREE II instrument. Average scaled scores across the six domains of the AGREE II and an overall independent score were calculated based on the formula provided. RESULTS The 2019 guideline scored high (range: 75-93%) in all domains except for the domain of applicability (34%). In the domain of rigour of development, significant improvements were noted in the 2019 guideline (median score: 7.0, interquartile range (IQR): 6.0-7.0) compared to the 2014 guideline (median: 5.0, IQR: 4.0-6.0) (p

Vision impairment can have a significant impact on the wellbeing and quality of life of an individual. Vision rehabilitation has the potential to improve these areas; however, four in five patients with vision impairment are not being referred to the appropriate services. Barriers to on-referral include, but are not limited to: (1) misunderstandings by both practitioners and patients alike regarding which individuals with vision impairment might benefit or qualify for low vision services; (2) lack of awareness of available services; (3) unfamiliarity with practice guidelines; (4) miscommunication between practitioners and patients; (5) required patient travel or limitations in access; and (6) the perceived costs of goods and services. Further, current referral patterns do not represent a holistic patient-centric approach. Vision-related quality of life questionnaires are tools which can assist health professionals in providing optimal individualised care. This review explores current evidence regarding low vision service delivery within Australia and globally, the impact of vision impairment on activities of daily living, the instruments used for the assessment of vision-related quality of life (VRQOL), competing priorities of individual needs in low vision services and rehabilitation, and provides recommendations for a more patient-centred model of care.

To assess the accuracy of cluster analysis-based models in predicting visual field (VF) defects from macular ganglion cell-inner plexiform layer (GCIPL) measurements in glaucomatous and healthy cohorts.GCIPL measurements were extracted from posterior pole optical coherence tomography (OCT), from locations corresponding to central VF test grids. Models incorporating cluster analysis methods and corrections for age and fovea to optic disc tilt were developed from 493 healthy participants, and 5th and 1st percentile limits of GCIPL thickness were derived. These limits were compared with pointwise 5th and 1st percentile limits by calculating sensitivities and specificities in an additional 40 normal and 37 glaucomatous participants, as well as applying receiver operating characteristic (ROC) curve analyses to assess the accuracy of predicting VF results from co-localised GCIPL measurements.Clustered models demonstrated globally low sensitivity, but high specificity in the glaucoma cohort (0.28-0.53 and 0.77-0.91, respectively), and high specificity in the healthy cohort (0.91-0.98). Clustered models showed similar sensitivities and superior specificities compared with pointwise methods (0.41-0.65 and 0.71-0.98, respectively). There were significant differences in accuracy between clusters, with relatively poor accuracy at peripheral macular locations (p 0.0001 for all comparisons).Cluster analysis-based models incorporating age correction and holistic consideration of fovea to optic disc tilt demonstrated superior performance in predicting VF results to pointwise methods in both glaucomatous and healthy eyes. However, relatively low sensitivity and poorer performance at the peripheral macula indicate that OCT in isolation may be insufficient to predict visual function across the macula accurately. With modifications to criteria for abnormality, the concepts suggested by the described normative models may guide prioritisation of VF assessment requirements, with the potential to limit excessive VF testing.

BACKGROUND In ageing populations, the prevalence of chronic diseases such as glaucoma is projected to increase, placing additional demands on limited health-care resources. In the UK, the demand for secondary care in hospital eye clinics was inflated by high rates of false positive glaucoma referrals. Collaborative care models incorporating referral refinement, whereby glaucoma suspect referrals are triaged by suitably trained optometrists through further testing, can potentially reduce false positive referrals. This study examined the impact of a referral refinement model on the accuracy of glaucoma referrals in Australia. METHODS Optometrist-initiated glaucoma suspect referrals to the Glaucoma Management Clinic (Sydney, Australia) were prospectively recruited. Glaucoma suspect referrals arising from two pathways were eligible for inclusion, either directly from a community optometrist (standard care) or following comprehensive assessment at the Centre for Eye Health (referral refinement). Main outcome measures were the positive predictive value and false positive rate of referrals. The impact of referral letter content on management outcomes was also investigated. RESULTS Of 464 referrals received between March 2015 and June 2018, 252 were for treatment of naive glaucoma suspects and eligible for inclusion. Following ophthalmological assessment, 45.6 per cent (n = 115/252) were prescribed treatment for open angle glaucoma or ocular hypertension. Positive predictive value of community optometry referrals was 33.8 per cent (n = 25/74) and 50.6 per cent (n = 90/178) following referral refinement. The first visit discharge (false positive) rate was 26 per cent (n = 19/74) for community referrals compared to four per cent (n = 8/178) with referral refinement. Positive predictive value increased with the number of abnormal clinical examination findings associated with referral (χ2 test, p

Purpose To identify patterns of age‐, gender‐ and refractive‐ related changes in Scheimpflug‐based anterior chamber depth across the central 8 mm of chamber width, to derive normative models, potentially useful for angle closure disease diagnosis. Methods This was a retrospective, cross‐sectional study. Scheimpflug photography was used to obtain anterior chamber depth measurements at 57 points across the central 8 mm of the chamber width from one eye of each healthy subject (male Caucasians (n = 189), female Caucasians (n = 186), male Asians (n = 165) and female Asians (n = 181)). Sliding window and nonlinear regression analysis was used to identify the age‐related changes in chamber depth. Hierarchical cluster analysis was used to identify test locations with statistically identical age‐related shifts, which were used to perform age‐correction for all subjects, resulting in normative distributions of chamber depth across the chamber width. The model was examined with and without the contribution of spherical equivalent refractive error. Results Distinct clusters, demonstrating statistically indistinguishable age‐related changes of chamber depth over time, were identified. These age‐related changes followed a nonlinear regression (fifth or sixth order polynomial). Females tended to have a greater rate of chamber depth shallowing. Incorporating refractive error into the model produced minimal changes to the fit relative to the ground truth. Comparisons with cut‐offs for angle closure from the literature showed that ageing alone was insufficient for identifying angle closure disease. Conclusions Age‐, ethnicity‐ and gender‐related differences need to be acknowledged in order to utilise anterior chamber depth data for angle closure disease diagnosis correctly. Ageing alone does not adequately account for the angle closure disease process.

SIGNIFICANCE Icare HOME rebound tonometry is increasingly adopted into clinical practice for IOP phasing of glaucoma patients and suspects. Because of measurement differences with applanation tonometry and diurnal fluctuations, interpretation of the IOP measured with Icare HOME phasing can be challenging. PURPOSE The purpose of this study was to use a large patient cohort to develop a practical, analytical tool for interpreting Icare HOME measurements with respect to applanation pressure. METHODS IOP measurements using the Icare HOME and an applanation tonometer were taken prospectively in 498 consecutive patients. Bland-Altman, frequency distribution, and linear regression analysis were applied to determine measurement differences. A novel criterion, Threshold Icare HOME IOP, was developed to assist identification of elevation above target applanation pressure, considering the expected diurnal variation and measurement variability. RESULTS Icare HOME tended to underestimate applanation tonometry (mean bias, -1.7 mmHg; 95% limits of agreement, -7.0 to +3.6). Overall, differences were within ±3 mmHg in 71.5% and ±5 mmHg in 92% of patients. Based on the novel criterion developed, Icare HOME measurements that exceed target applanation pressure by 6 mmHg or greater are generally outside the 95% limit of expected observations. CONCLUSIONS The Threshold Icare HOME IOP is a novel and practical criterion that can assist clinicians in their interpretation of Icare HOME phasing measurements with respect to target applanation pressures. Elevation above the expected thresholds may prompt closer monitoring or even modifications to glaucoma management.

Purpose To apply computational methods to model normal age-related changes in corneal parameters and to establish their association with demographic factors, thereby providing a framework for improved detection of subclinical corneal ectasia (SCE). Design Cross-sectional study. Methods One hundred seventeen healthy participants were enrolled from Centre for Eye Health (Sydney, Australia). Corneal thickness (CT), front surface sagittal curvature (FSSC), and back surface sagittal curvature (BSSC) measurements were extracted from 57 corneal locations from 1 eye per participant using the Pentacam HR. Cluster analyses were performed to identify locations demonstrating similar variations with age. Age-related changes were modeled using polynomial regression with sliding window methods, and model accuracy was verified with Bland–Altman comparisons. Pearson correlations were applied to examine the impacts of demographic factors. Results Concentric cluster patterns were observed for CT and FSSC but not for BSSC. Sliding window analyses were best fit with quartic and cubic regression models for CT and FSSC/BSSC, respectively. CT and FSSC sliding window models had narrower 95% limits of agreement compared with decade-based models (0.015 mm vs 0.017 mm and 0.14 mm vs 0.27 mm, respectively), but were wider for BSSC than decade-based models (0.73 mm vs 0.54 mm). Significant correlations were observed between CT and astigmatism (P = .02-.049) and FSSC and BSSC and gender (P = Conclusions The developed models robustly described aging variations in CT and FSSC; however, other mechanisms appear to contribute to variations in BSSC. These findings and the identified correlations provide a framework that can be applied to future model development and establishment of normal databases to facilitate SCE detection.

PURPOSE: To develop location specific models of normal, age-related changes in the macular ganglion cell layer (GCL) from optical coherence tomography (OCT). Using these OCT-derived models, we predicted visual field (VF) sensitivity and compared these results to actual VF sensitivities. DESIGN: Retrospective cohort study METHODS: Single eyes of 254 normal participants were retrospectively enrolled from the Centre for Eye Health (Sydney, Australia). Macular GCL measurements were obtained using Spectralis OCT. Cluster algorithms were performed to identify spatial patterns demonstrating similar age-related change. Quadratic and linear regression models were subsequently utilized to characterize age-related GCL decline. 40 participants underwent additional testing with Humphrey VFs, and 95% prediction intervals were calculated to measure the predictive ability of structure-function models incorporating cluster-based pooling, age-correction and consideration of spatial summation. RESULTS: Quadratic GCL regression models provided a superior fit (p =

CLINICAL RELEVANCE With equivalent inner retinal thickness measurements compared to a more conventional composite optical coherence tomography (OCT) protocol, Widefield optical coherence tomography (WF-OCT) is a clinically viable, time-saving option facilitating detection of ocular pathologies within the central 55° of the retina. PURPOSE To compare ganglion cell-inner plexiform layer (GCIPL) thicknesses obtained using a single WF-OCT scan and standard composite OCT scans acquired in 9 fields of gaze (9F-OCT). METHODS Thirteen healthy participants underwent WF-OCT and 9F-OCT using the Spectralis OCT. The GCIPL was automatically segmented with a manual review for 9F-OCT and was manually segmented for WF-OCT. After registration, differences in GCIPL thicknesses were compared using 95% confidence intervals computed from one-sample t-tests and Bland-Altman analyses. Location-specific differences in B-scan tilt were analysed using Spearman correlations and linear regression models. To determine whether B-scan tilt influences GCIPL measurements, regression models of tilt versus differences between perpendicular and axial GCIPL thickness were applied. RESULTS While scattered locations demonstrated significant GCIPL thickness differences between WF-OCT and 9F-OCT, most differences did not exceed the axial pixel resolution of the instrument of 3.87 µm. Bland-Altman analyses indicated no notable bias using WF-OCT. Moderate correlations indicating significant location-specific differences in B-scan tilt were observed for temporal, central and inferior B-scans (r = -0.62 to 0.72), with linear regression models predicting a maximum difference in the tilt of 4.65°. The quadratic regression model indicated that at tilts greater than 27.3°, perpendicular GCIPL measurements become increasingly thin relative to axial measurements. CONCLUSIONS GCIPL thicknesses and B-scan tilts from WF-OCT are comparable to 9F-OCT, indicating that WF-OCT can be applied clinically to obtain valid inner retinal OCT measurements over 55° of the central retina with relative ease. However, for peripheral locations, B-scan tilt may need to be considered when measuring GCIPL thicknesses.

ObjectivesThe Australian Government funded a nationwide diabetic retinopathy screening programme to improve visual outcomes for people with diabetes. This study examined the benefits and barriers of the programme, image interpretation pathways and assessed the characteristics of people who had their fundus photos graded by a telereading service which was available as a part of the programme.DesignMultimethod: survey and retrospective review of referral forms.SettingTwenty-two primary healthcare facilities from urban, regional, rural and remote areas of Australia, and one telereading service operated by a referral-only eye clinic in metropolitan Sydney, Australia.ParticipantsTwenty-seven primary healthcare workers out of 110 contacted completed a survey, and 145 patient referrals were reviewed.ResultsManifest qualitative content analysis showed that primary healthcare workers reported that the benefits of the screening programme included improved patient outcomes and increased awareness and knowledge of diabetic retinopathy. Barriers related to staffing issues and limited referral pathways. Image grading was performed by a variety of primary healthcare workers, with one responder indicating the utilisation of a diabetic retinopathy reading service. Of the people with fundus photos graded by the reading service, 26.2% were reported to have diabetes. Overall, 12.3% of eyes were diagnosed with diabetic retinopathy. Photo quality was rated as excellent in 46.2% of photos. Referral to an optometrist for diabetic retinopathy was recommended in 4.1% of cases, and to an ophthalmologist in 6.9% of cases.ConclusionsThis nationwide diabetic retinopathy screening programme was perceived to increase access to diabetic retinopathy screening in regional, rural and remote areas of Australia. The telereading service has diagnosed diabetic retinopathy and other ocular pathologies in images it has received. Key barriers, such as access to ophthalmologists and optometrists, must be overcome to improve visual outcomes.

The most effective measure to prevent or stop the spread of infectious diseases is the early identification and isolation of infected individuals through comprehensive screening. At present, in the COVID-19 pandemic, such screening is often limited to isolated regions as determined by local governments. Screening of potentially infectious individuals should be conducted through coordinated national or global unified actions. Our current research focuses on using resources to conduct comprehensive national and regional regular testing with a risk rate based, algorithmic guided, multiple-level, pooled testing strategy. Here, combining methodologies with mathematical logistic models, we present an analytic procedure of an overall plan for coordinating state, national, or global testing. The proposed plan includes three parts 1) organization, resource allocation, and distribution; 2) screening based on different risk levels and business types; and 3) algorithm guided, multiple level, continuously screening the entire population in a region. This strategy will overcome the false positive and negative results in the polymerase chain reaction (PCR) test and missing samples during initial tests. Based on our proposed protocol, the population screening of 300,000,000 in the US can be done weekly with between 15,000,000 and 6,000,000 test kits. The strategy can be used for population screening for current COVID-19 and any future severe infectious disease when drugs or vaccines are not available., Graphical abstract Unlabelled Image

Clinical relevance: Understanding the quality of the commonly used clinical practice guidelines can help busy clinicians in selecting appropriate guidelines for evidence-based eye care for people w...

We aimed to evaluate methods of extracting optical coherence tomography (OCT)-derived macular ganglion cell-inner plexiform layer (GCIPL) thickness measurements over retinal locations corresponding to standard visual field (VF) test grids. A custom algorithm was developed to automatically extract GCIPL thickness measurements from locations corresponding to Humphrey Field Analyser 10-2 and 30-2 test grids over Goldmann II, III and V stimulus sizes from a healthy cohort of 478 participants. Differences between GCIPL thickness measurements based on VF test grids (VF-based paradigms) and the 8 × 8 grid, as per instrument review software, were analyzed, as were impacts of fovea to optic disc tilt and areas over which GCIPL thickness measurements were extracted. Significant differences between the VF-based paradigms and the 8 × 8 grid were observed at up to 55% of locations across the macula, with the greatest deviations at the fovea (median 25.5 μm, 95% CI 25.24–25.72 μm, P

Diagnosis and monitoring of keratoconus is increasingly being conducted with the aid of imaging equipment such as corneal aberrometry. There is a need to also know the confidence with which ocular aberration measurements can be made.To assess the repeatability of lower- and higher-order aberration measurements in patients with keratoconus using the irx3 wavefront aberrometer (Imagine Eyes, Orsay, France) and evaluate correlations with corneal curvature.The irx3 wavefront aberrometer was used to measure bilateral lower- and higher-order ocular aberrations on 33 participants with keratoconus. Three measurements were taken from each eye to determine the repeatability of lower-order aberrations (quantified as sphere and cylinder in dioptres) and higher-order aberration co-efficients (up to eighth order in micrometres), coma, trefoil and total higher-order aberration root mean square (in micrometres). Corneal curvature was measured using the Pentacam HR system (OCULUS, Wetzlar, Germany).Repeat measurements for lower-order aberrations resulted in larger co-efficients of repeatability than higher-order aberrations. Similarly, larger co-efficients of repeatability between repeated measures across all Zernike co-efficients were observed in eyes with severe keratoconus (that is, corneal curvature 52-D) compared to eyes with flatter corneas. The difference between repeated measures tended to be significant for the lower-order aberrations regardless of corneal curvature. The highest correlations with corneal curvature for right and left eyes respectively, were identified for total higher-order aberration root mean square (r = 0.92, p 0.001 and r = 0.91, p 0.001), followed closely by coma (r = -0.93, p 0.001 and r = -0.86, p 0.001) and the Z (3, -1) co-efficient (r = -0.92, p 0.001 and r = -0.86, p 0.001 for right and left eyes, respectively).Lower-order aberrations tended to be less repeatable, indicating that instrument variability must be considered when monitoring progression. Total higher-order aberration root mean square and third-order aberrations, in particular the vertical coma Z (3, -1) co-efficient, demonstrated a stronger correlation with corneal curvature than the lower-order aberrations.

Background The aim of this study is to evaluate the diagnosis, staging, imaging and management preferences, and the effect of advanced imaging among practising optometrists in age-related macular degeneration (AMD). Methods Up to 20 case vignettes (computer-based case simulations) were completed online in a computer laboratory in random order by 81 practising optometrists of Australia. Each case presented findings from a randomly selected patient seen previously at the Centre for Eye Health for a macular assessment in the following order: case history, preliminary tests and colour fundus photography. Participants were prompted to provide their diagnosis, management and imaging preference. One additional imaging result (either modified fundus photographs and infrared images, fundus autofluorescence, or optical coherence tomography [OCT]) was then provided and the questions repeated. Finally, all imaging results were provided and the questions repeated a third time. Results A total of 1,436 responses were analysed. The presence of macular pathology in AMD was accurately detected in 94 per cent of instances. The overall diagnostic accuracy of AMD was 61 per cent using colour fundus photography. This improved by one per cent using one additional imaging modality and a further four per cent using all imaging. Across all responses, a greater improvement in the diagnostic accuracy of AMD occurred following the presentation of OCT findings (versus other modalities). OCT was the most preferred imaging modality for AMD, while multimodal imaging was of greatest benefit in cases more often misdiagnosed using colour fundus photography alone. Overall, the cohort also displayed a tendency to underestimate disease severity. Conclusion Despite reports that imaging technologies improve the stratification of AMD, our findings suggest that this effect may be small when applied among practising optometrists without additional or specific training.

Supplemental digital content is available in the text., SIGNIFICANCE This study resulted in the identification of an optic nerve head (ONH) feature associated with tilted optic discs, which might potentially contribute to ONH pathologies. Knowledge of such findings will enhance clinical insights and drive future opportunities to understand disease processes related to tilted optic discs. PURPOSE The aim of this study was to identify novel retinal nerve fiber layer (RNFL) anomalies by evaluating tilted optic discs using optical coherence tomography. An observed retinal nerve fiber protrusion was further investigated for association with other morphological or functional parameters. METHODS A retrospective review of 400 randomly selected adult patients with ONH examinations was conducted in a referral-only, diagnostic imaging center. After excluding other ONH pathologies, 215 patients were enrolled and evaluated for optic disc tilt and/or torsion. Gross anatomical ONH features, including size and rim or parapapillary region elevation, were assessed with stereoscopic fundus photography. Optical coherence tomography provided detailed morphological information of individual retinal layers. Statistical analysis was applied to identify significant changes between individual patient cohorts. RESULTS A dome-shaped hyperreflective RNFL bulge, protruding into the neurosensory retina at the optic disc margins, was identified in 17 eyes with tilted optic discs. Available follow-up data were inconclusive regarding natural changes with this ONH feature. This RNFL herniation was significantly correlated with smaller than average optic disc size (P = .005), congenital disc tilt (P < .0001), and areas of rim or parapapillary elevation (P < .0001). CONCLUSIONS This study reports an RNFL protrusion associated with tilted optic discs, which has not previously been assessed as an independent ONH structure. The feature is predominantly related to congenital crowded, small optic discs and variable between patients. This study is an important first step to elucidate diagnostic capabilities of tilted disc morphological changes and understanding associated functional deficits.

SIGNIFICANCE This article shows that self-tonometry can provide robust measures of diurnal intraocular pressure (IOP) and also detect changes to IOP in response to treatment within a short period of monitoring. These advances in IOP monitoring may contribute to improved management of glaucoma patients and suspects. PURPOSE The aim of this study was to prospectively investigate the utility of rebound self-tonometry performed over several weeks for detecting diurnal IOP fluctuations in glaucoma patients and suspects and also initial response to topical treatment in glaucoma patients. METHODS Forty patients were recruited following glaucoma-specific examination. Subsequent to successful training with the iCare HOME tonometer, patients were instructed to measure IOP, in a sitting position, four times a day over 4 to 6 weeks. Date, time, laterality, and IOP downloaded from the tonometer and clinical examination data, including applanation IOP and corneal thickness, were analyzed. A user satisfaction survey was also administered at study completion. t Test and analysis of variance were used to compare groups and IOP across days. Pearson correlation was used to compare measurements to Goldmann applanation tonometry and IOP measurements from the first day/s to the overall mean IOP. RESULTS Twenty-seven patients (18 suspects and 9 glaucoma patients) completed data collection. Patients self-measured IOP on 118 (±29) occasions for 40 (±7.4) days. Two dominant patterns of fluctuation were revealed: peak IOP upon awakening (n = 11) and at midday (n = 13). Diurnal IOP measured in the first 7 days showed strong correlation to diurnal IOP across the entire study period (r2 = 0.82, P < .0001). Within 24 hours of treatment commencement (latanoprost 0.005% ophthalmic solution), IOP reduced from 23.9 (±5.2) to 16.1 (±2.6) mmHg. Overall, patients rated the instrument as easy to use, although difficulties with correct alignment were expressed. CONCLUSIONS Rebound self-tonometry demonstrated utility for measuring diurnal IOP fluctuations in most patients, hence enhancing management of patient with or at risk of developing glaucoma.

The use of advanced imaging in clinical practice is emerging and the use of this technology by optometrists in assessing patients with age-related macular degeneration is of interest. Therefore, this study explored contemporary, self-reported patterns of practice regarding age-related macular degeneration diagnosis and management using a cross-sectional survey of optometrists in Australia and New Zealand.Practising optometrists were surveyed on four key areas, namely, demographics, clinical skills and experience, assessment and management of age-related macular degeneration. Questions pertaining to self-rated competency, knowledge and attitudes used a five-point Likert scale.Completed responses were received from 127 and 87 practising optometrists in Australia and New Zealand, respectively. Advanced imaging showed greater variation in service delivery than traditional techniques (such as slitlamp funduscopy) and trended toward optical coherence tomography, which was routinely performed in age-related macular degeneration by 49 per cent of respondents. Optical coherence tomography was also associated with higher self-rated competency, knowledge and perceived relevance to practice than other modalities. Most respondents (93 per cent) indicated that they regularly applied patient symptoms, case history, visual function results and signs from traditional testing, when queried about their management of patients with age-related macular degeneration. Over half (63 per cent) also considered advanced imaging, while 31 per cent additionally considered all of these as well as the disease stage and clinical guidelines. Contrary to the evidence base, 68 and 34 per cent rated nutritional supplements as highly relevant or relevant in early age-related macular degeneration and normal aging changes, respectively.These results highlight the emergence of multimodal and advanced imaging (especially optical coherence tomography) in the assessment of age-related macular degeneration by optometrists. Clinically significant variations in self-rated test competency and the understanding regarding nutritional supplements for different stages of age-related macular degeneration suggest that further work to up-skill optometrists may be required.

ObjectivesMany chronic eye conditions are managed within public hospital ophthalmology clinics resulting in encumbered wait lists. Integrated care schemes can increase system capacity. In order to direct implementation of a public hospital-based integrated eye care model, this study aims to evaluate the quality of referrals for new patients through information content, assess triage decisions of newly referred patients and evaluate the consistency of referral content for new patients referred multiple times.DesignA retrospective and prospective review of all referral forms for new patients referred to a public hospital ophthalmology clinic between January 2016 and September 2017, and September 2017 and August 2018, respectively.SettingA referral-only public hospital ophthalmology clinic in metropolitan Sydney, Australia.Participants418 new patients on existing non-urgent wait lists waiting to be allocated an initial appointment, and 528 patients who were newly referred.Primary and secondary outcome measuresThe primary outcome was the information content of referrals for new patients. The secondary outcomes were triage outcomes for new incoming referrals, and the number of new patients with multiple referrals.ResultsOf the wait-listed referrals, 0.2% were complete in referral content compared with 9.8% of new incoming referrals (pConclusionsMost referrals were incomplete in content, leading to triage based on limited clinical information. Some new patients were referred multiple times with their second referral containing a similar amount of content as their first. Lengthy wait lists could be prevented by improving administrative processes and communication between the referral centre and referrers. The future implementation of an integrated eye care model at the study setting could sustainably cut wait lists for patients with chronic eye conditions.

Background Accurate diagnosis in patients presenting with lesions at various locations within the visual pathway is challenging. This study investigated functional and structural changes secondary to such lesions to identify patterns useful to guide early and effective management. Methods Over 10,000 records from patients referred for optic nerve head assessment were reviewed and 31 patients with a final diagnosis of likely neuropathic lesions posterior to the eye were included in the current study. Fundus photographs, optic coherence tomography images and visual field tests were evaluated for changes with respect to retinal nerve fibre layer topography and prediction of structure-function paradigms. Emerging clinical patterns were examined for their consistency with the likely anatomical origin of the underlying insult in the presence of varying diagnoses. Results Data from patients with lesions along the visual system allowed identification of retinal nerve fibre layer asymmetry correlated with visual field defects and ganglion cell analysis. Bilateral discordance in retinal nerve fibre loss easily discernible from an altered pattern of the temporal-superior-nasal-inferior-temporal curve was characteristic for post-chiasmal lesions. These sometimes-subtle changes supported diagnosis in cases with multiple aetiologies or with ambiguous visual field analysis and/or ganglion cell loss. Conclusion Intricate knowledge of the retinal architecture and projections allows coherent predictions of functional and structural deficits following various lesions affecting the visual pathway. The integration of adjunct imaging and retinal nerve fibre layer thinning will assist clinicians to guide clinical investigations toward a likely diagnosis in the light of significant individual variations. The case series presented in this study aids in differential diagnosis of retrograde optic neuropathies by using retinal nerve fibre layer asymmetric patterns as an important clinical marker.

Purpose Goldmann size V (GV) test stimuli are less variable with a greater dynamic range and have been proposed for measuring contrast sensitivity instead of size III (GIII). Since GIII and GV operate within partial summation, we hypothesise that actual GV (aGV) thresholds could predict GIII (pGIII) thresholds, facilitating comparisons between actual GIII (aGIII) thresholds with pGIII thresholds derived from smaller GV variances. We test the suitability of GV for detecting visual field (VF) loss in patients with early glaucoma, and examine eccentricity‐dependent effects of number and depth of defects. We also hypothesise that stimuli operating within complete spatial summation (‘spatially equated stimuli’) would detect more and deeper defects. Methods Sixty normal subjects and 20 glaucoma patients underwent VF testing on the Humphrey Field Analyzer using GI‐V sized stimuli on the 30‐2 test grid in full threshold mode. Point‐wise partial summation slope values were generated from GI‐V thresholds, and we subsequently derived pGIII thresholds using aGV. Difference plots between actual GIII (aGIII) and pGIII thresholds were used to compare the amount of discordance. In glaucoma patients, the number of ‘events’ (points below the 95% lower limit of normal), defect depth and global indices were compared between stimuli. Results 90.5% of pGIII and aGIII points were within ±3 dB of each other in normal subjects. In the glaucoma cohort, there was less concordance (63.2% within ±3 dB), decreasing with increasing eccentricity. GIII found more defects compared to GV‐derived thresholds, but only at outermost test locations. Greater defect depth was found using aGIII compared to aGV and pGIII, which increased with eccentricity. Global indices revealed more severe loss when using GIII compared to GV. Spatially equated stimuli detected the greatest number of ‘events’ and largest defect depth. Conclusions Whilst GV may be used to reliably predict GIII values in normal subjects, there was less concordance in glaucoma patients. Similarities in ‘event’ detection and defect depth in the central VF were consistent with the fact that GIII and GV operate within partial summation in this region. Eccentricity‐dependent effects in ‘events’ and defect depth were congruent with changes in spatial summation across the VF and the increase in critical area with disease. The spatially equated test stimuli showed the greatest number of defective locations and larger sensitivity loss.

In our intermediate-tier glaucoma care clinic, we demonstrate fair to moderate agreement in gonioscopy examination between optometrists and ophthalmologists, but excellent agreement when considering open versus closed angles. We highlight the need for increased consistency in the evaluation and recording of angle status using gonioscopy.The consistency of gonioscopy results obtained by different clinicians is not known but is important in moving toward practice modalities such as telemedicine and collaborative care clinics. The purpose of this study was to evaluate the description and concordance of gonioscopy results among different practitioners.The medical records of 101 patients seen within a collaborative care glaucoma clinic who had undergone gonioscopic assessment by two clinicians (one optometrist and either one general ophthalmologist [n = 50] or one glaucoma specialist [n = 51]) were reviewed. The gonioscopy records were evaluated for their descriptions of deepest structure seen, trabecular pigmentation, iris configuration, and other features. These were compared between clinicians (optometrist vs. ophthalmologist) and against the final diagnosis.Overall, 51.9 and 59.8% of angles were graded identically in terms of deepest visible structure when comparing between optometrist versus general ophthalmologist and optometrist versus glaucoma specialist, respectively. The concordance increased when considering ±1 of the grade (67.4 and 78.5%, respectively), and agreement with the final diagnosis was high (90%). Variations in angle grading other than naming structures were observed (2.0, 30, and 3.9% for optometrist, general ophthalmologist, and glaucoma specialist, respectively). Most of the time, trabecular pigmentation or iris configuration was not described.Fair to moderate concordance in gonioscopy was achieved between optometrists and ophthalmologists in a collaborative care clinic in which there is consistent feedback and clinical review. To move toward unified medical records and a telemedicine model, improved consistency of record keeping and angle description is required.

BackgroundOptical coherence tomography is commonly used to measure the retinal nerve fibre layer thickness in both normal and diseased eyes; however, variation among normal eyes is common and may limit the usefulness of the results. The aim of this study was to explore the interocular asymmetries in retinal nerve fibre layer thickness in a group of normal eyes and to investigate the influence of blood vessel diameter on local retinal nerve fibre layer thickness.MethodsIn this prospective study, retinal nerve fibre layer thickness and blood vessel diameter across 100 healthy participants were measured using two optical coherence tomography instruments. Individuals were categorised into two groups based on the presence or absence of interocular retinal nerve fibre layer thickness asymmetry beyond the 75th percentile of all participants.ResultsThe superonasal sectoral retinal nerve fibre layer thickness was significantly greater in the left eye compared to the right, across all three sectors. Mean blood vessel diameter showed a corresponding difference in thickness at one of the superonasal sectors. Linear regression showed a positive and moderate correlation between blood vessel diameter and focal retinal nerve fibre layer thickness. This trend persisted across both arteries and veins, but veins showed larger variability between left and right eye in participants with marked superonasal retinal nerve fibre layer asymmetry.ConclusionRetinal nerve fibre layer thickness and blood vessel diameter vary significantly between eyes even in healthy individuals. These asymmetries in a normal population should be taken into consideration when interpreting the retinal nerve fibre layer thickness measurements from optical coherence tomography to assist in distinguishing normal variations from disease.

Standard automated perimetry (SAP), the most common form of perimetry used in clinical practice, is associated with high test variability, impacting clinical decision making and efficiency. Contrast sensitivity isocontours (CSIs) may reduce test variability in SAP by identifying regions of the visual field with statistically similar patterns of change that can be analysed collectively and allow a point (disease)-to-CSI (normal) comparison in disease assessment as opposed to a point (disease)-to-point (normal) comparison. CSIs in the central visual field however have limited applicability as they have only been described using visual field test patterns with low, 6° spatial sampling. In this study, CSIs were determined within the central 20° visual field using the 10-2 test grid paradigm of the Humphrey Field Analyzer which has a high 2° sampling frequency. The number of CSIs detected in the central 20° visual field was greater than previously reported with low spatial sampling and stimulus size dependent: 6 CSIs for GI, 4 CSIs for GII and GIII, and 3 CSIs for GIV and GV. CSI number and distribution were preserved with age. Use of CSIs to assess visual function in age-related macular degeneration (AMD) found CSI guided analysis detected a significantly greater deviation in sensitivity of AMD eyes from normal compared to a standard clinical pointwise comparison (−1.40 ± 0.15 dB vs −0.96 ± 0.15 dB; p

Purpose Leading causes of irreversible blindness such as age-related macular degeneration (AMD) and glaucoma can, respectively, lead to central or peripheral vision loss. The ability of sufferers to process visual motion information can be impacted even during early stages of eye disease. We used head-mounted display virtual reality as a tool to better understand how vision changes caused by eye diseases directly affect the processing of visual information critical for self-motion perception. Methods Participants with intermediate AMD or early manifest glaucoma with near-normal visual acuities and visual fields were recruited for this study. We examined their experiences of self-motion in depth (linear vection), spatial presence, and cybersickness when viewing radially expanding patterns of optic flow simulating different speeds of self-motion in depth. Viewing was performed with the head stationary (passive condition) or while making lateral-sway head movements (active conditions). Results Participants with AMD (i.e., central visual field loss) were found to have greater vection strength and spatial presence, compared to participants with normal visual fields. However, participants with glaucoma (i.e., peripheral visual field loss) were found to have lower vection strength and spatial presence, compared to participants with normal visual fields. Both AMD and glaucoma groups reported reduced severity in cybersickness compared to healthy normals. Conclusions These findings strongly support the view that perceived self-motion is differentially influenced by peripheral versus central vision loss, and that patients with different visual field defects are oppositely biased when processing visual cues to self-motion perception.

ObjectivesDiabetic eye disease is a leading cause of blindness but can be mitigated by regular eye assessment. A framework of issues, developed from the literature of barriers to eye assessment, was used to structure an examination of perceptions of a new model of care for diabetic retinopathy from the perspective of staff using the model, and health professionals referring patients to the new service.DesignMultimethod: interviews and focus groups, and a separate survey.SettingA new clinic based on an integrated model of care was established at a hospital in outer metropolitan Sydney, Australia in 2017. Funded jointly by Centre for Eye Health (CFEH) and the hospital, the clinic was equipped and staffed by optometrists who work alongside the ophthalmologists in the existing hospital eye clinic.ParticipantsFive (of seven) hospital staff working in the clinic (ophthalmologists and administrative officers) or referring to it from other departments (endocrinologists); nine optometrists from CFEH who developed or worked in the clinic; 10 community-based optometrists as potential referrers.ResultsThe new clinic was considered to have addressed known barriers to eye assessment, including access, assistance for patients unable/unwilling to organise eye checks and efficient management of human resources. The clinic optimised known drivers of this model of care: providing clear scope of practice and protocols for shared care between optometrists and ophthalmologists, good communication between referrers and eye professionals and a collegial approach promoting interprofessional trust. Remaining areas of concern were few referrals from general practitioners, fewer referrals from hospital endocrinologists than expected and issues with stretched administrative capacity. There were also perceived mismatches between the priorities of hospital management and aims of the clinic.ConclusionsThe new model was considered to have addressed many of the barriers to assessment. While there remain issues with the model, there were also unexpected benefits.

Purpose The purpose of this study was to examine changes in the ganglion cell layer (GCL) of individuals with intermediate age-related macular degeneration (AMD) using grid-wise analysis for macular optical coherence tomography (OCT) volume scans. We also aim to validate the use of age-correction functions for GCL thickness in diseased eyes. Methods OCT macular cube scans covering 30° × 25° were acquired using Spectralis spectral-domain OCT for 87 eyes with intermediate AMD, 77 age-matched normal eyes, and 254 non-age-matched normal eyes. The thickness of the ganglion cell layer (GCL) was defined after segmentation at 60 locations across an 8 × 8 grid centered on the fovea, where each grid location covered 0.74 mm2 (approximately 3° × 3°) within the macula. Each GCL location of normal eyes (n = 77) were assigned to a specific iso-ganglion cell density cluster in the macula, based on patterns of age-related GCL thickness loss. Analyses were then performed comparing AMD GCL grid-wise data against corresponding spatial clusters, and significant AMD GCL thickness changes were denoted as values outside the 95% distribution limits. Results Analysis of GCL thickness changes revealed significant differences between spatial clusters, with thinning toward the fovea, and thickening toward the peripheral macula. The direction of GCL thickness changes in AMD were associated more so with thickening than thinning in all analyses. Results were corroborated by the application of GCL thickness age-correction functions. Conclusions GCL thickness changed significantly and nonuniformly within the macula of intermediate AMD eyes. Further characterization of these changes is critical to improve diagnoses and monitoring of GCL-altering pathologies.

Purpose Optic nerve head (ONH) assessment and its interpretation in healthy patients and those with glaucoma remains a pivotal topic specifically considering rapid advancements in imaging technologies. We undertook a large-scale, mixed cohort, comparative study to assess the correlation of optic disc measurements between different imaging modalities and investigated the impact of patient and disc associated parameters. Methods ONH sizes were obtained from one randomly selected eye of each of 209 patients using stereophotography, confocal scanning laser ophthalmoscopy and two different optical coherence tomographers (OCT). Patient related data, glaucoma status and optic disc variables, specifically oblique insertion, torsion, presence of beta PPA and spherical equivalent were recorded. Measurements between imaging modalities were analysed using Pearson correlation, linear regression analysis and Blend-Altman plots. Individual variables were compared applying multivariate regression analysis, ANOVA and chi square statistics was used to determine correlations between patient and clinical characteristics. Results Absolute measurements significantly differed between imaging modalities generally producing smaller measurements for OCT derived measurements of Bruch’s membrane opening (BMO). Pairwise correlations between imaging modalities were between 0.83 and 0.93 for discs without myopia, oblique insertion, or beta PPA. These features impacted on measurements for individual modalities and consequently contributed to inconsistencies and variability. Conclusion In comparison to planimetry, OCT derived BMO measurements are more variable in the presence of oblique insertion, beta PPA or magnification errors due to myopia. Impact of these factors, however, differs between instruments and needs to be considered to accurately interpret optic disc features in particular within the context of glaucoma diagnosis.

Purpose To develop and test the performance of a deep learning-based algorithm for glaucomatous disc identification using monoscopic fundus photographs. Design Fundus photograph database study. Participants Four thousand three hundred ninety-four fundus photographs, including 3768 images from previous Sydney-based clinical studies and 626 images from publicly available online RIM-ONE and High-Resolution Fundus (HRF) databases with definitive diagnoses. Methods We merged all databases except the HRF database, and then partitioned the dataset into a training set (80% of all cases) and a testing set (20% of all cases). We used the HRF images as an additional testing set. We compared the performance of the artificial intelligence (AI) system against a panel of practicing ophthalmologists including glaucoma subspecialists from Australia, New Zealand, Canada, and the United Kingdom. Main Outcome Measures The sensitivity and specificity of the AI system in detecting glaucomatous optic discs. Results By using monoscopic fundus photographs, the AI system demonstrated a high accuracy rate in glaucomatous disc identification (92.7%; 95% confidence interval [CI], 91.2%–94.2%), achieving 89.3% sensitivity (95% CI, 86.8%–91.7%) and 97.1% specificity (95% CI, 96.1%–98.1%), with an area under the receiver operating characteristic curve of 0.97 (95% CI, 0.96–0.98). Using the independent online HRF database (30 images), the AI system again accomplished high accuracy, with 86.7% in both sensitivity and specificity (for ophthalmologists, 75.6% sensitivity and 77.8% specificity) and an area under the receiver operating characteristic curve of 0.89 (95% CI, 0.76–1.00). Conclusions This study demonstrated that a deep learning-based algorithm can identify glaucomatous discs at high accuracy level using monoscopic fundus images. Given that it is far easier to obtain monoscopic disc images than high-quality stereoscopic images, this study highlights the algorithm's potential application in large population-based disease screening or telemedicine programs.

Purpose To evaluate the influence of different clinical examination techniques, including optic nerve head (ONH) photography, visual field tests, and adjunct imaging on the diagnosis of glaucoma by Australian and New Zealand optometrists. The effect of a short-term, didactic teaching module on these is also explored. Methods Clinical data of 30 patients previously seen at the Centre for Eye Health was collected and compiled into glaucoma diagnostic assessment modules. Each of six modules contained different combinations of clinical examination results and required a classification of the cases as normal, suspicious or glaucoma. A cohort of 54 Australian and New Zealand optometrists were recruited for the study and allocated into two cohorts. The intervention group completed a glaucoma training course prior to the assessment while the control group completed the assessment without additional training. Diagnostic accuracy was compared between modules and optometrist groups. Results High false negative rates were observed with ONH photography, which were drastically reduced with the addition of visual field, albeit at the cost of increased false positive rates. Addition of adjunct imaging techniques partially compensated for the increase in the false positive rate from the visual field, but had limited effect on false negative rate. Educational intervention resulted in larger improvement in the diagnostic ability when multiple imaging modalities were provided. Conclusion The study highlighted the importance of combining both structural and functional assessments in glaucoma. Current imaging technology demonstrated limited usefulness for event diagnosis due to the persistent difficulties of defining structural and functional loss in glaucoma, thus highlighting the need for new glaucoma assessment techniques. Short-term didactic teaching programs may only result in limited improvement of glaucoma diagnostic ability in optometrists, and hence, it may need to be combined with long-term and/or non-didactic training components to obtain a greater effect.

Purpose To determine the locus of test locations that exhibit statistically similar age-related decline in sensitivity to light increments and age-corrected contrast sensitivity isocontours (CSIs) across the central visual field (VF). We compared these CSIs with test point clusters used by the Glaucoma Hemifield Test (GHT). Methods Sixty healthy observers underwent testing on the Humphrey Field Analyzer 30-2 test grid using Goldmann (G) stimulus sizes I-V. Age-correction factors for GI-V were determined using linear regression analysis. Pattern recognition analysis was used to cluster test locations across the VF exhibiting equal age-related sensitivity decline (age-related CSIs), and points of equal age-corrected sensitivity (age-corrected CSIs) for GI-V. Results There was a small but significant test size-dependent sensitivity decline with age, with smaller stimuli declining more rapidly. Age-related decline in sensitivity was more rapid in the periphery. A greater number of unique age-related CSIs was revealed when using smaller stimuli, particularly in the mid-periphery. Cluster analysis of age-corrected sensitivity thresholds revealed unique CSIs for GI-V, with smaller stimuli having a greater number of unique clusters. Zones examined by the GHT consisted of test locations that did not necessarily belong to the same CSI, particularly in the periphery. Conclusions Cluster analysis reveals statistically significant groups of test locations within the 30-2 test grid exhibiting the same age-related decline. CSIs facilitate pooling of sensitivities to reduce the variability of individual test locations. These CSIs could guide future structure-function and alternate hemifield asymmetry analyses by comparing matched areas of similar sensitivity signatures.

Purpose To characterize macular ganglion cell layer (GCL) changes with age and provide a framework to assess changes in ocular disease. This study used data clustering to analyze macular GCL patterns from optical coherence tomography (OCT) in a large cohort of subjects without ocular disease. Methods Single eyes of 201 patients evaluated at the Centre for Eye Health (Sydney, Australia) were retrospectively enrolled (age range, 20-85); 8 × 8 grid locations obtained from Spectralis OCT macular scans were analyzed with unsupervised classification into statistically separable classes sharing common GCL thickness and change with age. The resulting classes and gridwise data were fitted with linear and segmented linear regression curves. Additionally, normalized data were analyzed to determine regression as a percentage. Accuracy of each model was examined through comparison of predicted 50-year-old equivalent macular GCL thickness for the entire cohort to a true 50-year-old reference cohort. Results Pattern recognition clustered GCL thickness across the macula into five to eight spatially concentric classes. F-test demonstrated segmented linear regression to be the most appropriate model for macular GCL change. The pattern recognition-derived and normalized model revealed less difference between the predicted macular GCL thickness and the reference cohort (average ± SD 0.19 ± 0.92 and -0.30 ± 0.61 μm) than a gridwise model (average ± SD 0.62 ± 1.43 μm). Conclusions Pattern recognition successfully identified statistically separable macular areas that undergo a segmented linear reduction with age. This regression model better predicted macular GCL thickness. The various unique spatial patterns revealed by pattern recognition combined with core GCL thickness data provide a framework to analyze GCL loss in ocular disease.

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.

Eye health-care in Australia encompasses patients with chronic disorders being referred to ophthalmologists for detailed assessment and subsequent management. An increasing case load and relative decrease in ophthalmologists predicted over the next few years portend of an upcoming bottleneck in care delivery. To improve the efficiency and effectiveness of patient care within a rapidly changing health system, we propose that minor adjustments to existing services could improve the proficiency of resources. Such changes will require service providers to rethink their positions and roles and actively collaborate with each other for improved patient outcomes.

A familial form of lupus, termed exfoliative cutaneous lupus erythematosus (ECLE) has been recognized for decades in German shorthaired pointer dogs (GSP). Previous studies were suggestive of autosomal recessive inheritance. The disease presents as a severe dermatitis with age of onset between 16 and 40 weeks, and mirrors cutaneous lupus erythematosus (CLE) in humans. Lameness and, in advanced cases, renal disease may be present. Most affected dogs are euthanized before reaching the age of 4 years. The diagnosis is made by clinical observations and microscopic examination of skin biopsies. In humans, many different forms of CLE exist and various genes and chromosomal locations have been implicated. The large number of potential candidate loci combined with often weak association prevented in depth screening of the dog population thus far. During the course of our studies, we developed a colony of dogs with ECLE as a model for human CLE and the genetic analysis of these dogs confirmed the autosomal recessive mode of inheritance of CLE in GSPs. Using canine patient material, we performed a genome-wide association study (GWAS) to identify the genomic region harboring the gene involved in the development of the disease in GSPs. We identified a SNP allele on canine chromosome 18 that segregated with the disease in the 267 dogs tested. The data generated should allow identification of the mutant gene responsible for this form of cutaneous lupus erythematosus in dogs and assist in the understanding of the development of similar disease in humans.

Over 200 mutations in the retina specific member of the ATP-binding cassette transporter super-family (ABCA4) have been associated with a diverse group of human retinal diseases. The disease mechanisms, and genotype–phenotype associations, nonetheless, remain elusive in many cases. As orthologous genes are commonly mutated in canine models of human blinding disorders, canine ABCA4 appears to be an ideal candidate gene to identify and study sequence changes in dogs affected by various forms of inherited retinal degeneration. However, the size of the gene and lack of haplotype assignment significantly limit targeted association and/or linkage approaches. This study assessed the naturally observed sequence diversity of ABCA4 in the dog, identifying 80% of novel variations. While none of the observed polymorphisms have been associated with blinding disorders to date, breed and potentially disease specific haplotypes have been identified. Moreover, a tag SNP map of 17 (15) markers has been established that accurately predicts common ABCA4 haplotypes (frequency > 5%) explaining >85% (>80%) of the observed genetic diversity and will considerably advance future studies. Our sequence analysis of the complete canine ABCA4 coding region will clearly provide a baseline and tools for future association studies and comparative genomics to further delineate the role of ABCA4 in canine blinding disorders.

Purpose To investigate the effect of stimulus size and disease status on the structure-function relationship within the central retina, we correlated the differential light sensitivity (DLS) with Goldmann stimulus size I to V (GI-V) and optical coherence tomography (OCT) derived in vivo ganglion cell count per stimulus area (GCc) within the macular area in normal subjects and patients with early glaucoma. Methods Humphrey Field Analyzer 10-2 visual field data with GI through V and Spectralis OCT macular ganglion cell layer (GCL) thickness measurements were collected from normal and early glaucoma cohorts including 25 subjects each. GCc was calculated from GCL thickness data and correlated with DLSs for different stimulus sizes. Results Correlation coefficients attained with smaller stimulus size were higher compared to larger stimulus sizes in both normal (GI-GII: R2 = 0.41-0.43, GIII-GV: R2 = 0.16-0.41) and diseased cohorts (GI-GII: R2 = 0.33-0.41, GIII-GV: R2 = 0.19-0.36). Quadratic regression curves for combined GI to V data demonstrated high correlation (R2= 0.82-0.90) and differed less than 1 dB of visual sensitivity within the GCc range between cohorts. The established structure-function relationship was compatible with a histologically derived model correlation spanning the range predicted by stimulus sizes GI to GIII. Conclusions Stimulus sizes within critical spatial summation area (GI-II) improved structure-function correlations in the central visual field. The structure-function relationship was identical in both normal and diseased cohort when GI to GV data were combined. Congruency of GI and GII structure-function correlation with those previously derived with GIII from more peripheral locations further suggests that the structure-function relationship is governed by the number of ganglion cell per stimulus area.

Background The Heidelberg Retina Tomograph (HRT) is a commonly-used clinical instrument for glaucoma diagnosis; however, the repeatability of the two most commonly used analysis tools, Moorfield regression analysis (MRA) and ‘glaucoma probability score’ (GPS) is not known and could have significant implications for patients at risk or suspected of developing glaucoma. Thus, the intra-visit repeatability of the HRT3 (an objective measure of instrument-induced variability) was investigated in a glaucoma suspect cohort. Methods Two repeat 15° × 15° optic nerve head scans were taken from 164 eyes of 84 patients using the HRT (HRT3, software version 3) during a single visit. The variability of global and sectoral rim area, rim volume and GPS were analysed with and without image alignment using SPSS 22.0. Repeatability was evaluated as absolute difference between the two measurements. Results Repeatability of the global rim area, rim volume and GPS were high with and without image registration. Variability increased by a small, yet significant amount without image alignment (p

PURPOSE: Drusen alters retinal architecture in early age-related macular degeneration (AMD). However, abnormalities also may exist in drusen-free areas of the AMD retina. This study examines retinal thickness above drusen relative to drusen-free areas in the same patient and a normal population. METHODS: Patients with early to intermediate AMD (n = 122) or no disease (n = 30) were examined at the Center for Eye Health. Spectral domain optical coherence tomography (SD-OCT) scans through single, isolated druse (n = 125) or confluent drusen (n = 54) were obtained. The thickness of individual retinal layers was measured above the druse and in a drusen-free area, 150 μm from the drusen edge. RESULTS: Intraeye comparisons found total retinal thickness above drusen was 16 ± 0.6% less than drusen-free areas. Thinning was mostly in the retinal pigment epithelium/photoreceptor layer (32 ± 1% reduction) and the outer nuclear layer (22 ± 1% reduction). Confluent drusen showed similar thinning of the outer retina as well as inner retina loss (5%). Thinning was strongly correlated with drusen height, but only modestly correlated with drusen width. When compared to the normal population, retinal thickness above drusen and drusen-free areas were significantly reduced. CONCLUSIONS: We confirm outer retina thinning above drusen in early/intermediate AMD compared to drusen-free areas in the same retina or a normal population. Interestingly, drusen-free areas in AMD patients were not the same as control patients suggesting "normal" areas of the AMD retina are abnormal. The strong correlation between retinal thinning and drusen height, rather than width, suggests current grading systems for AMD may need refinement.

PURPOSE: The detection of changes in the retinal nerve fiber layer (RNFL) as measured by optical coherence tomography (OCT) is crucial in glaucoma diagnosis and management. We investigated the short-term repeatability of peripapillary RNFL measurements in a commercially available spectral domain OCT focusing on a broad clinical spectrum of patients. METHODS: Two consecutive peripapillary RNFL measurements were taken on 227 eyes with Cirrus HD-OCT (Carl Zeiss Meditec, Version 6.5 software) using the optic disc 200 × 200 protocol. Repeatability was assessed as Bland-Altman limits of agreement and intraclass coefficients (ICCs). RESULTS: Limits of agreement showed the greatest variability in the superior RNFL quadrant at ±7.5 μm and the least variability in the temporal quadrant at ±5.2 μm. The short-term repeatability for the average RNFL thickness resulted in an ICC of 0.98 and variability of 3.81 μm. Individual quadrants were similar, excepting the nasal RNFL quadrant with an ICC of 0.94. Inferior and temporal quadrants were the most repeatable with a variability of 2 to 3% instrument error. CONCLUSIONS: Cirrus HD-OCT has excellent short-term repeatability for peripapillary RNFL measurements in a mixed patient cohort. Retinal nerve fiber layer measurements are less reliable in the nasal RNFL quadrant. As other quadrants are used in glaucoma diagnosis, the detection of glaucomatous progression would be reliable.

Purpose Previous studies confirmed that optometrists have access to and confidence in applying clinical tests recommended for glaucoma assessment. Less is known about factors best predicting compliance with national clinical guidelines and thus by inference, the provision of suitable care by primary care ophthalmic practitioners. We utilised the unique two-tiered profession (therapeutic and non-therapeutic scope of practice) in Australia and New Zealand to assess the prospective adherence to glaucoma guidelines dependent on the clinician's background. Methods Australian and New Zealand optometrists were surveyed on ophthalmic techniques for glaucoma assessment, criteria for the evaluation of the optic nerve head, glaucoma risk categories and review times while also recording background, training, and experience. Parameters identifying progression/conversion and patients' risk levels were analysed comparatively to ophthalmologists' opinions. Linear regression analysis identified variables significantly improving the likelihood of concordance with guidelines. Results Reported application of techniques complied well with glaucoma guidelines although gonioscopy and pachymetry, pupil dilation for optic nerve head examination, and acquisition of permanent records were less frequently employed. The main predictors for entry-level diagnostic standards were therapeutic endorsement together with the associated knowledge of relevant guidance and procedural confidence. Other findings suggested a potential underestimation in the value of optic disc size and intraocular pressure for the prediction of glaucoma risk, while optometrists more frequently relied on the outcomes of non-standardised automated perimetry and auxiliary imaging. Conclusions Optometrists in Australia and New Zealand may not always exercise optimal clinical acumen regarding techniques/criteria for glaucoma diagnosis. Therapeutic endorsement was gradually adopted in different jurisdictions in various forms since 1999 and is mandatory for registration since late 2014. The result of the two-tiered optometric cohorts suggest that inclusion of therapeutic training as part of the core training is likely a key factor to enhanced compliance with glaucoma guidelines. Improved adherence to the current clinical standards should positively impact on the facilitation of appropriate glaucoma diagnosis and management. Obligatory knowledge and possibly accreditation of available guidelines might ensure a uniform standard in glaucoma testing protocols in concordance with compulsory entry-level skills.

Optimizing patient management will reduce unnecessary vision loss in glaucoma through early detection. One method is the introduction of collaborative care schemes between optometrists and ophthalmologists.We conducted a retrospective study to evaluate the impact of the Centre for Eye Health (CFEH) on glaucoma patient outcomes and management in primary optometric care.Patients referred to CFEH by optometrists for a glaucoma assessment were eligible for this study if written consent was provided (500 participants were randomly chosen).Clinical data were classified according to disease risk and implemented patient care and analysed against the original diagnosis and patient parameters, followed by statistical analysis.Two main parameters were evaluated; suitable referral of patients for glaucoma condition assessment and appropriate implementation of follow-up care.The majority of patients referred for glaucoma assessment (86.2%) were classified as glaucoma suspects or likely to have glaucoma, indicating suitable referral of patients for a CFEH evaluation. Further, the involvement of CFEH resulted in a false positive rate of 7.8% for those patients who proceeded to ophthalmological care. However, long-term optometric patient care was not maintained for up to a third of primarily lower risk patients.The investigated collaborative eye health-care model led to a substantial improvement in appropriate referrals of glaucoma patients to ophthalmologists and could be suitable for optimizing patient care and utilization of resources. Improvement in follow-up of patients by optometrists is required to minimize inappropriately discontinued patient care.

Cone–rod dystrophies (crd) represent a group of progressive inherited blinding diseases characterized by primary dysfunction and loss of cone photoreceptors accompanying or preceding rod death. Recessive crd type 1 was described in dogs associated with an RPGRIP1 exon 2 mutation, but with lack of complete concordance between genotype and phenotype. This review highlights role of the RPGRIP1, a component of complex protein networks, and its function in the primary cilium, and discusses the potential mechanisms of genotype–phenotype discordance observed in dogs with the RPGRIP1 mutation.

Mutations in the bestrophin-1 gene (BEST1) are an important cause of inherited retinal disorders. Hitherto, over 100 unique allelic variants have been linked to the human BEST1 (hBEST1), and associated with disease phenotypes, broadly termed as bestrophinopathies. A spontaneous animal model recapitulating BEST1-related phenotypes, canine multifocal retinopathy (cmr), is caused by mutations in the canine gene ortholog (cBEST1). We have recently characterized molecular consequences of cmr, demonstrating defective protein trafficking as a result of G161D (cmr2) mutation. To further investigate the pathological effects of BEST1 missense mutations, canine and human peptide fragments derived from the protein sequence have been studied in silico as models for early events in the protein folding. The results showed that G161D as well as I201T substitutions cause severe conformational changes in the structure of bestrophin-1, suggesting protein misfolding as an underlying disease mechanism. The comparative modeling studies expand our insights into BEST1 pathogenesis.

PURPOSE. Canine multifocal retinopathy (cmr) is an autosomal recessive disorder of multiple dog breeds. The disease shares a number of clinical and pathologic similarities with Best macular dystrophy (BMD), and cmr is proposed as a new large animal model for Best disease. METHODS. cmr was characterized by ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1 (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid 5- and 3-RACE. Expression of the canine gene transcripts and protein was analyzed by Northern and Western blotting and immunocytochemistry. All exons and the flanking splice junctions were screened by direct sequencing. RESULTS. The clinical phenotype and pathology of cmr closely resemble lesions of BMD. Canine VMD2 spans 13.7 kb of genomic DNA on CFA18 and shows a high level of conservation among eukaryotes. The transcript is predominantly expressed in RPE/choroid and encodes bestrophin, a 580-amino acid protein of 66 kDa. Immunocytochemistry of normal canine retina demonstrated specific localization of protein to the RPE basolateral plasma membranes. Two disease-specific sequence alterations were identified in the canine VMD2 gene: a C73T stop mutation in cmr1 and aG 482A missense mutation in cmr2. CONCLUSIONS. The authors propose these two spontaneous mutations in the canine VMD2 gene, which cause cmr, as the first naturally occurring animal model of BMD. Further development of the cmr models will permit elucidation of the complex molecular mechanism of these retinopathies and the development of potential therapies. (Invest Ophthalmol Vis Sci. 2007; 48:1959‐1967) DOI:10.1167/iovs.06-1374

Progressive rod-cone degeneration (prcd) is a late-onset, autosomal recessive photoreceptor degeneration of dogs, and a homolog for some forms of human retinitis pigmentosa (RP). Previously, the disease relevant interval was reduced to a 106 Kb region on CFA9, and a common phenotype-specific haplotype was identified in all affected dogs from several different breeds, and breed varieties. Screening of a canine retinal EST library identified partial cDNAs for novel candidate genes in the disease relevant interval. The complete cDNA of one of these, PRCD, was cloned in dog, human and mouse. The gene codes for a 54 amino acid (aa) protein in dog and human, and 53 aa protein in the mouse; the first 24 aa, coded for by exon 1, are highly conserved in 14 vertebrate species. A homozygous mutation (TGC → TAC) in the second codon shows complete concordance with the disorder in 18 different dog breeds/breed varieties tested. The same homozygous mutation was identified in a human patient from Bangladesh with autosomal recessive (ar) RP. Expression studies support the predominant expression of this gene in the retina, with equal expression in the retinal pigment epithelium (RPE), photoreceptors and ganglion cell layers. This study provides strong evidence that a mutation in the novel gene, PRCD, is the cause of autosomal recessive retinal degeneration in both dogs and man.