Optometry and Vision Sciences - Research Publications
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ItemVictorian evolution of inherited retinal diseases natural history registry (VENTURE study): Rationale, methodology and initial participant characteristics(WILEY, 2022-06-12)BACKGROUND: Emerging treatments are being developed for inherited retinal diseases, requiring a clear understanding of natural progression and a database of potential participants for clinical trials. This article describes the rationale, study design and methodology of the Victorian Evolution of inherited retinal diseases NaTUral history REgistry (VENTURE), including data from the first 150 participants enrolled. METHODS: VENTURE collects retrospective and prospective data from people with inherited retinal diseases. Following registration, participants are asked to attend a baseline examination using a standardised protocol to confirm their inherited retinal disease diagnosis. Examination procedures include (i) retinal function, using visual acuity and perimetry; (ii) retinal structure, using multimodal imaging and (iii) patient-reported outcomes. Participants' molecular diagnoses are obtained from their clinical records or through targeted-panel genetic testing by an independent laboratory. Phenotype and genotype data are used to enrol participants into disease-specific longitudinal cohort sub-studies. RESULTS: From 7 July 2020 to 30 December 2021, VENTURE enrolled 150 registrants (138 families) and most (63%) have a rod-cone dystrophy phenotype. From 93 participants who have received a probable molecular diagnosis, the most common affected genes are RPGR (13% of all registrants), USH2A (10%), CYP4V2 (7%), ABCA4 (5%), and CHM (5%). Most participants have early to moderate vision impairment, with over half (55%) having visual acuities of better than 6/60 (20/200) at registration. CONCLUSIONS: The VENTURE study will complement existing patient registries and help drive inherited retinal disease research in Australia, facilitating access to research opportunities for individuals with inherited retinal diseases.
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ItemPoint-of-care tools to support optometric care provision to people with age-related macular degeneration: A randomised, placebo-controlled trial(WILEY, 2022-03-14)PURPOSE: Age-related macular degeneration (AMD) is a leading cause of vision impairment. This randomised placebo-controlled trial investigated whether point-of-care tools can improve optometrists' AMD knowledge and/or care provision. METHODS: Australian optometrists (n = 31) completed a demographics survey and theoretical AMD case study multiple-choice questions (MCQs) to assess their confidence in AMD care provision and AMD knowledge. Participants were then randomly assigned to one of three point-of-care tools (online 'Classification of Age-related macular degeneration and Risk Assessment Tool' (CARAT), paper CARAT, or 'placebo') to use when providing care to their subsequent 5-10 AMD patients. Participants self-audited the compliance of their AMD care to best practice for these patients, and a similar number of consecutive patients seen prior to enrolment. Post-intervention, participants retook the AMD knowledge MCQs and confidence survey. RESULTS: A total of 29 participants completed the study. At the study endpoint, clinical confidence relative to baseline improved with the paper CARAT, relative to placebo, for knowledge of AMD risk factors, asking patients about these factors and referring for medical retinal sub-specialist care. There were no between-group differences for the change in AMD knowledge scores. Considering record documentation for patients with any AMD severity, there were no significant between-group differences for documenting patient risk factors, AMD severity, clinical examination techniques or management. In a sub-analysis, the change from baseline in compliance for documenting discussions about patient smoking behaviours for early AMD patients was higher with use of the online CARAT relative to placebo (p = 0.04). For patients with intermediate AMD, the change from baseline in documenting the risk of progression to late AMD was greater among practitioners who used the paper CARAT, relative to placebo (p = 0.04). CONCLUSIONS: This study demonstrates that point-of-care clinical tools can improve practitioner confidence and aspects of the documentation of AMD clinical care by optometrists as assessed by self-audit.
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ItemOrientation pinwheels in primary visual cortex of a highly visual marsupial(AMER ASSOC ADVANCEMENT SCIENCE, 2022-09-30)Primary visual cortices in many mammalian species exhibit modular and periodic orientation preference maps arranged in pinwheel-like layouts. The role of inherited traits as opposed to environmental influences in determining this organization remains unclear. Here, we characterize the cortical organization of an Australian marsupial, revealing pinwheel organization resembling that of eutherian carnivores and primates but distinctly different from the simpler salt-and-pepper arrangement of eutherian rodents and rabbits. The divergence of marsupials from eutherians 160 million years ago and the later emergence of rodents and rabbits suggest that the salt-and-pepper structure is not the primitive ancestral form. Rather, the genetic code that enables complex pinwheel formation is likely widespread, perhaps extending back to the common therian ancestors of modern mammals.
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ItemInterobserver Agreement of Electrode to Retina Distance Measurements in a Second-Generation (44-Channel) Suprachoroidal Retinal Prosthesis.(Association for Research in Vision and Ophthalmology (ARVO), 2022-09-01)PURPOSE: The electrode to retina (ER) distance is an important contributory factor to the safety and efficacy of a suprachoroidal retinal prosthesis. Measuring ER distance may be performed by different observers during multisite studies. The aim of this study was to assess the interobserver agreement in measuring ER distance. METHODS: Three independent, trained observers measured ER distance from the center of each suprachoroidal electrode to the inner retinal pigment epithelium in spectral-domain optical coherence tomography (SD-OCT) B-scans. A total of 121 ER distance measurements from 77 B-scans collected over 5 months from one subject implanted with a second-generation 44-channel suprachoroidal retinal prosthesis (NCT03406416) were made by each observer. RESULTS: ER distance ranged from 208 to 509 µm. Pearson's correlation coefficient (ρ) showed agreement of 0.99 (95% confidence interval [CI] = 0.98-0.99) in measuring ER for each pairwise comparison. The mean difference in ER distance between observers ranged from 2.4 to 6.4 µm with pairwise limits of agreement (95% CI) of ±20 µm (5.5% of mean). Intraclass correlation coefficient (ICC) showed agreement of 0.98 (95% CI = 0.97-0.99) between observers. CONCLUSIONS: There is high agreement in measuring ER distances for suprachoroidal retinal prostheses using our systematic approach between multiple, trained observers, supporting the use of a single observer for each image. TRANSLATIONAL RELEVANCE: High interobserver agreement outcomes indicate that multiple, trained observers can be used to take ER measurements across different images in suprachoroidal retinal prosthesis studies. This improves multisite study efficiency and gives confidence in interpreting results relating to the safety and efficacy of suprachoroidal retinal prostheses.
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ItemExpression of muscarinic receptor subtypes in tree shrew ocular tissues and their regulation during the development of myopia(MOLECULAR VISION, 2009-03-02)PURPOSE: Muscarinic receptors are known to regulate several important physiologic processes in the eye. Antagonists to these receptors such as atropine and pirenzepine are effective at stopping the excessive ocular growth that results in myopia. However, their site of action is unknown. This study details ocular muscarinic subtype expression within a well documented model of eye growth and investigates their expression during early stages of myopia induction. METHODS: Total RNA was isolated from tree shrew corneal, iris/ciliary body, retinal, choroidal, and scleral tissue samples and was reverse transcribed. Using tree shrew-specific primers to the five muscarinic acetylcholine receptor subtypes (CHRM1-CHRM5), products were amplified using polymerase chain reaction (PCR) and their identity confirmed using automated sequencing. The expression of the receptor proteins (M1-M5) were also explored in the retina, choroid, and sclera using immunohistochemistry. Myopia was induced in the tree shrew for one or five days using monocular deprivation of pattern vision, and the expression of the receptor subtypes was assessed in the retina, choroid, and sclera using real-time PCR. RESULTS: All five muscarinic receptor subtypes were expressed in the iris/ciliary body, retina, choroid, and sclera while gene products corresponding to CHRM1, CHRM3, CHRM4, and CHRM5 were present in the corneal samples. The gene expression data were confirmed by immunohistochemistry with the M1-M5 proteins detected in the retina, choroid, and sclera. After one or five days of myopia development, muscarinic receptor gene expression remained unaltered in the retinal, choroidal, and scleral tissue samples. CONCLUSIONS: This study provides a comprehensive profile of muscarinic receptor gene and protein expression in tree shrew ocular tissues with all receptor subtypes found in tissues implicated in the control of eye growth. Despite the efficacy of muscarinic antagonists at inhibiting myopia development, the genes of the muscarinic receptor subtypes are neither regulated early in myopia (before measurable axial elongation) nor after significant structural change.
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ItemNo Preview AvailableOptimising visual attention in children with autism spectrum disorder: a comparison of fixation distributions viewing singing and speech(Association for Research in Vision and Ophthalmology, 2017-06-01)Purpose : Many children with autism spectrum disorder (ASD) are at risk of social isolation and limited social development due to difficulties with gaze and visual attention to people. Studies have shown that children with ASD may prefer music to other stimuli. We hypothesised that a short video of a singer would elicit more attention to the performer, particularly to her face, than a video of her reading a story and that the child’s familiarity with the song and story would enhance attention. Methods : 16 children aged 7-10 (14 M, 2 F) with ASD took part. Stimuli were 4 videos 1 minute long. Content was a favourite song or story of the child, along with a song and story which were the same for all children. The performer, her clothing, lighting and sound level were the same across tasks. Props were a pair of drums for the songs and a storybook of similar size for the stories. Eye movements were recorded with an Eyelink 1000; areas of interest (AOIs) were defined for the face, prop and body. 3-way repeated measures ANOVAs were used to examine the proportion of total dwell time, the proportion of total fixations and pupil area for each AOI in each trial. Results : For dwell time proportion, a significant interaction was found for familiarity*AOI (F=7.45, p=.004), with gaze time to the face being increased for familiar trials (Table 1). Similarly, medium*AOI was significant (F=6.01, p=.013), with increased gaze time to the face and body and decreased time to the prop for the songs (Table 2). The same patterns were seen for proportion of fixation counts to the AOIs (familiarity*AOI F=4.97, p =.016; medium*AOI F=10.33, p=.001). For the pupil, only familiarity and AOI were significant; pupils were larger for familiar stimuli (F=16.70, p=.001) and for the face and prop (F=6.8, p=.015), with the body eliciting less dilation. Conclusions : As hypothesised, the videos of singing attracted children's gaze to the performer more than did those of her reading a story. Familiarity with the material being performed also attracted more attention to her face. Familiarity and gaze to the face also increased arousal, as indexed by pupil dilation. Observation by children with ASD of a singer, particularly one performing their favourite songs, may be a useful intervention for improving their social engagement skills.
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ItemNo Preview AvailableToward Universal Eye Health Coverage-Key Outcomes of the World Health Organization Package of Eye Care Interventions: A Systematic Review.(American Medical Association (AMA), 2022-12-01)IMPORTANCE: Despite persistent inequalities in access to eye care services globally, guidance on a set of recommended, evidence-based eye care interventions to support country health care planning has not been available. To overcome this barrier, the World Health Organization (WHO) Package of Eye Care Interventions (PECI) has been developed. OBJECTIVE: To describe the key outcomes of the PECI development. EVIDENCE REVIEW: A standardized stepwise approach that included the following stages: (1) selection of priority eye conditions by an expert panel after reviewing epidemiological evidence and health facility data; (2) identification of interventions and related evidence for the selected eye conditions from a systematic review of clinical practice guidelines (CPGs); stage 2 included a systematic literature search, screening of title and abstracts (excluding articles that were not relevant CPGs), full-text review to assess disclosure of conflicts of interest and affiliations, quality appraisal, and data extraction; (3) expert review of the evidence extracted in stage 2, identification of missed interventions, and agreement on the inclusion of essential interventions suitable for implementation in low- and middle-income resource settings; and (4) peer review. FINDINGS: Fifteen priority eye conditions were chosen. The literature search identified 3601 articles. Of these, 469 passed title and abstract screening, 151 passed full-text screening, 98 passed quality appraisal, and 87 were selected for data extraction. Little evidence (≤1 CPG identified) was available for pterygium, keratoconus, congenital eyelid disorders, vision rehabilitation, myopic macular degeneration, ptosis, entropion, and ectropion. In stage 3, domain-specific expert groups voted to include 135 interventions (57%) of a potential 235 interventions collated from stage 2. After synthesis across all interventions and eye conditions, 64 interventions (13 health promotion and education, 6 screening and prevention, 38 treatment, and 7 rehabilitation) were included in the PECI. CONCLUSIONS AND RELEVANCE: This systematic review of CPGs for priority eye conditions, followed by an expert consensus procedure, identified 64 essential, evidence-based, eye care interventions that are required to achieve universal eye health coverage. The review identified some important gaps, including a paucity of high-quality, English-language CPGs, for several eye diseases and a dearth of evidence-based recommendations on eye health promotion and prevention within existing CPGs.
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ItemTopographical Distribution and Phenotype of Resident Meibomian Gland Orifice Immune Cells (MOICs) in Mice and the Effects of Topical Benzalkonium Chloride (BAK)(MDPI, 2022-09-01)Meibomian gland orifices (MGOs) are located along the eyelid margin and secrete meibum into the tear film. The profile of resident innate immune cells (ICs) at this site is not well understood. The distribution and phenotype of resident ICs around MGOs in mice was investigated and herein defined as MGO-associated immune cells (MOICs). The effect of topical 0.1% benzalkonium chloride (BAK) on MOICs was also assessed. Eyelids from healthy CD11ceYFP and Cx3cr1gfp/gfp mice aged three or seven months were compared. ICs were identified as CD11c+, Cx3cr1+, and MHC-II+ using four-colour immunostaining and confocal microscopy. MOIC density was variable but clustered around MGOs. There were more CD11c+ MOICs in three-month-old compared with seven-month-old mice (three-month-old: 893 ± 449 cells/mm2 vs. seven-month-old: 593 ± 493 cells/mm2, p = 0.004). Along the eyelid margin, there was a decreasing gradient of CD11c+ MOIC density in three-month-old mice (nasal: 1003 ± 369 cells/mm2, vs. central: 946 ± 574 cells/mm2, vs. temporal: 731 ± 353 cells/mm2, p = 0.044). Cx3cr1-deficient mice had two-fold fewer MHC-II+ MOICs, suggesting a role for Cx3cr1 receptor signaling in meibomian gland surveillance. CD11c+ MOIC density was lower in BAK-exposed eyes compared to saline-treated controls, suggesting a change in homeostasis. This study provides novel insight into resident ICs located at MGOs, and their contribution to MG homeostasis.
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ItemDetecting glaucoma from multi-modal data using probabilistic deep learning(FRONTIERS MEDIA SA, 2022-09-29)OBJECTIVE: To assess the accuracy of probabilistic deep learning models to discriminate normal eyes and eyes with glaucoma from fundus photographs and visual fields. DESIGN: Algorithm development for discriminating normal and glaucoma eyes using data from multicenter, cross-sectional, case-control study. SUBJECTS AND PARTICIPANTS: Fundus photograph and visual field data from 1,655 eyes of 929 normal and glaucoma subjects to develop and test deep learning models and an independent group of 196 eyes of 98 normal and glaucoma patients to validate deep learning models. MAIN OUTCOME MEASURES: Accuracy and area under the receiver-operating characteristic curve (AUC). METHODS: Fundus photographs and OCT images were carefully examined by clinicians to identify glaucomatous optic neuropathy (GON). When GON was detected by the reader, the finding was further evaluated by another clinician. Three probabilistic deep convolutional neural network (CNN) models were developed using 1,655 fundus photographs, 1,655 visual fields, and 1,655 pairs of fundus photographs and visual fields collected from Compass instruments. Deep learning models were trained and tested using 80% of fundus photographs and visual fields for training set and 20% of the data for testing set. Models were further validated using an independent validation dataset. The performance of the probabilistic deep learning model was compared with that of the corresponding deterministic CNN model. RESULTS: The AUC of the deep learning model in detecting glaucoma from fundus photographs, visual fields, and combined modalities using development dataset were 0.90 (95% confidence interval: 0.89-0.92), 0.89 (0.88-0.91), and 0.94 (0.92-0.96), respectively. The AUC of the deep learning model in detecting glaucoma from fundus photographs, visual fields, and both modalities using the independent validation dataset were 0.94 (0.92-0.95), 0.98 (0.98-0.99), and 0.98 (0.98-0.99), respectively. The AUC of the deep learning model in detecting glaucoma from fundus photographs, visual fields, and both modalities using an early glaucoma subset were 0.90 (0.88,0.91), 0.74 (0.73,0.75), 0.91 (0.89,0.93), respectively. Eyes that were misclassified had significantly higher uncertainty in likelihood of diagnosis compared to eyes that were classified correctly. The uncertainty level of the correctly classified eyes is much lower in the combined model compared to the model based on visual fields only. The AUCs of the deterministic CNN model using fundus images, visual field, and combined modalities based on the development dataset were 0.87 (0.85,0.90), 0.88 (0.84,0.91), and 0.91 (0.89,0.94), and the AUCs based on the independent validation dataset were 0.91 (0.89,0.93), 0.97 (0.95,0.99), and 0.97 (0.96,0.99), respectively, while the AUCs based on an early glaucoma subset were 0.88 (0.86,0.91), 0.75 (0.73,0.77), and 0.92 (0.89,0.95), respectively. CONCLUSION AND RELEVANCE: Probabilistic deep learning models can detect glaucoma from multi-modal data with high accuracy. Our findings suggest that models based on combined visual field and fundus photograph modalities detects glaucoma with higher accuracy. While probabilistic and deterministic CNN models provided similar performance, probabilistic models generate certainty level of the outcome thus providing another level of confidence in decision making.
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ItemAssociation between systemic omega-3 polyunsaturated fatty acid levels, and corneal nerve structure and function(SPRINGERNATURE, 2022-09-26)BACKGROUND: Omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory and neuroprotective properties. This study sought to determine the relationship between corneal parameters and systemic omega-3 fatty acid levels. METHODS: Forty-seven participants with no/mild peripheral neuropathy (26 with diabetes and 21 without) underwent comprehensive ocular surface and systemic PUFA assessments. Corneal anatomical parameters were assessed using in vivo confocal microscopy. Corneal sensitivity was measured using non-contact esthesiometry. Relationships between systemic PUFA levels and corneal parameters were evaluated with multiple linear regression, adjusted for age, sex, neuropathy symptom score, and presence of diabetes and dry eye disease. The relationship between corneal nerve fibre length (CNFL) and corneal sensitivity threshold was evaluated. RESULTS: The median Omega-3 Index, a measure of erythrocyte EPA and DHA, was 5.21% (interquartile range: 4.44-5.94%) in the study population. Mean ( ± SD) CNFL was 13.53 ± 3.37 mm/mm2. Multiple linear regression showed that Omega-3 Index (β = 0.33; p = 0.02), age (β = -0.46; p = 0.001) and diabetes (β = -0.30; p = 0.03) were independently associated with CNFL (R2 = 0.39, p = 0.002). In a separate model, DHA (β = 0.32; p = 0.027) and age (β = -0.41; p = 0.003) were associated with CNFL (R2 = 0.37, p = 0.003). Neither systemic EPA nor omega-6 fatty acid levels correlated with CNFL. There was no association between PUFA levels and corneal sensitivity or corneal immune cell density. A negative correlation was found between CNFL and corneal sensation thresholds to a cooled stimulus in diabetes participants, in the central (ρ = -0.50; p = 0.009) and peripheral (ρ = -0.50; p = 0.01) cornea. CONCLUSIONS: A positive relationship between the systemic Omega-3 Index and corneal nerve parameters suggests omega-3 PUFA intake may influence corneal nerve architecture.