A multinational survey of potential participant perspectives on ocular gene therapy.

Amidst rapid advancements in ocular gene therapy, understanding patient perspectives is crucial for shaping future treatment choices and research directions. This international cross-sectional survey evaluated knowledge, attitudes, and perceptions of ocular genetic therapies among potential recipients with inherited retinal diseases (IRDs). Survey instruments included the Attitudes to Gene Therapy-Eye (AGT-Eye), EQ-5D-5L, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and Patient Attitudes to Clinical Trials (PACT-22) instruments. This study included 496 participant responses (89% adults with IRDs; 11% parents/guardians/carers) from 35 countries, with most from the United States of America (USA; 69%) and the United Kingdom (11%). Most participants (90%) indicated they would likely accept gene therapy if it was available, despite only 45% agreeing that they had good knowledge of gene therapy. The main sources of information were research registries (60% of participants) and the internet (61%). Compared to data from our recently published Australian national survey of people with IRDs (n = 694), USA respondents had higher knowledge of gene therapy outcomes, and Australian respondents indicated a higher perceived value of gene therapy treatments. Addressing knowledge gaps regarding outcomes and financial implications will be central to ensuring informed consent, promoting shared decision-making, and the eventual clinical adoption of genetic therapies.

The Better Operative Outcomes Software Tool (BOOST) Prospective Study: Improving the Quality of Cataract Surgery Outcomes in Low-Resource Settings.

PURPOSE: Post-operative vision impairment is common among patients who have undergone cataract surgery in low-resource settings, impacting quality of clinical outcomes and patient experience. This prospective, multisite, single-armed, pragmatic validation study aimed to assess whether receiving tailored recommendations via the free Better Operative Outcomes Software Tool (BOOST) app improved surgical outcomes, as quantified by post-operative unaided distance visual acuity (UVA) measured 1-3 days after surgery. METHODS: During the baseline data collection round, surgeons in low and middle-income countries recorded clinical characteristics of 60 consecutive cataract cases in BOOST. Additional data on the causes of poor outcomes from 20 consecutive cases with post-operative UVA of <6/60 (4-12 weeks post-surgery) were entered to automatically generate tailored recommendations for improvement, before 60 additional consecutive cases were recorded during the follow-up study round. Average UVA was compared between cases recorded in the baseline study round and those recorded during follow-up. RESULTS: Among 4,233 cataract surgeries performed by 41 surgeons in 18 countries, only 2,002 (47.3%) had post-operative UVA 6/12 or better. Among the 14 surgeons (34.1%) who completed both rounds of the study (1,680 cases total), there was no clinically significant improvement in post-operative average UVA (logMAR units ±SD) between baseline (0.50 ± 0.37) and follow-up (0.47 ± 0.36) rounds (mean improvement 0.03, p = 0.486). CONCLUSIONS: Receiving BOOST-generated recommendations did not result in improved UVA beyond what could be expected from prospective monitoring of surgical outcomes alone. Additional research is required to assess whether targeted support to implement changes could potentiate the uptake of app-generated recommendations and improve outcomes.

Quality of Refractive Error Care in Cambodia: An Unannounced Standardized Patient Study.

PURPOSE: Quality-of-care in refractive error services is essential, as it directly affects vision outcomes, wellbeing, educational attainment, and workforce participation. In Cambodia, uncorrected refractive error is a leading cause of mild and moderate vision impairment in adults. We evaluated the quality of refractive error care in Cambodia by estimating the proportion of prescribed and dispensed spectacles appropriate for people's refractive error needs and factors associated with spectacle quality. METHODS: A cross-sectional protocol was employed with 18 Khmer-speaking adult participants observing testing procedures in 156 optical services across six provinces in 2022. A total of 496 dispensed spectacles were assessed against spectacle quality indicators. RESULTS: The analysis revealed that 35.1% of dispensed spectacles were of optimal quality. The most common error observed in sub-optimal spectacles was the presence of horizontal prism outside of tolerance limits. The study also found that 44.0% of emmetrope visits involved unnecessary prescription spectacle recommendations, and 18.3% of written prescriptions did not correspond with dispensed spectacles. Sex differences were observed, with men predominantly providing refractive error care and women more likely to be unnecessarily recommended prescription spectacles. CONCLUSION: The findings highlight the importance of prioritizing quality-of-care in refractive error services. A key recommendation is to consider regulatory mechanisms to ensure optical services employ appropriately qualified staff. Additionally, efforts should be made to eliminate unnecessary prescriptions -- especially for emmetropes and females -- standardize written prescriptions, ensure consistent pupil distance measurements, reduce reliance on autorefraction, and address the gender imbalance in the refractive error workforce.

Prospective, Randomized Controlled Trial of Cataract Surgery vs Combined Cataract Surgery With Insertion of iStent Inject.

PURPOSE: To evaluate the efficacy and safety of combined cataract surgery with insertion of an ab interno trabecular microbypass device (iStent Inject, Glaukos Corporation) compared to cataract surgery alone in patients with mild-to-moderate glaucoma. DESIGN: Prospective, randomized, assessor-masked controlled trial at a single centre. PARTICIPANTS: Eyes with visually-significant cataract and mild-to-moderate glaucoma with preoperative intraocular pressure (IOP) of 12 to 30 mmHg on 0 to 3 ocular hypotensive medications. METHODS: Participants eyes were randomized (2017-2020) 1:1 to combined cataract surgery with iStent Inject (treatment group, n = 56) or cataract surgery alone (control group, n = 48), and followed up for 2 years. MAIN OUTCOME MEASURES: The co-primary effectiveness endpoints were the number of ocular hypotensive medications and IOP at 24-months post-surgery. The secondary effectiveness endpoints were ocular comfort as measured by the Ocular Surface Disease Index (OSDI) and vision-related quality of life as measured by the Glaucoma Activity Limitation Questionnaire (GAL-9) at 24-months. Safety measures included postoperative visual acuity, any unplanned return to the operating theatre, adverse events, and complications. RESULTS: Participants (67.3% male) were aged 53 to 85 years, and treatment groups were similar in terms of mean medicated IOP (treatment group 17.7 mmHg ± 4.0; control group 17.1 mmHg ± 3.1), and number of ocular hypotensive medications (treatment group 1.69 ± 1.05; control group 1.80 ± 1.22) at baseline. At 24 months, the number of ocular hypotensive medications were 0.7 ± 0.9 in the treatment groups compared to 1.5 ± 1.9 in the control group, with an adjusted difference of 0.6 fewer medications per eye in the treatment group (95% CI 0.2-1.1, P = 0.008). In the treatment group, 57% of eyes were on no glaucoma medications compared to 36% in the control group. There was no significant difference in IOP between the 2 groups beyond the 4-weeks. There were no differences in patient-reported outcomes between the 2 groups. The visual outcomes and safety profiles were similar between the 2 groups. CONCLUSIONS: Combined cataract surgery with iStent Inject achieved a clinically- and statistically-significantly greater reduction in ocular hypotensive medication usage at 24-months compared to cataract surgery alone, with no significant difference in IOP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

EQ-5D-5L health utility scores in Australian adults with inherited retinal diseases: A cross-sectional survey.

PURPOSE: Economic evaluations of interventions for ocular disease require utility scores that accurately represent quality of life in the target population. This study aimed to describe the distribution of EQ-5D-5L utility values among Australian adults with symptomatic inherited retinal diseases (IRDs) and to assess the relationship between these scores and vision-related quality of life. METHODS: A survey was administered predominantly online in 2021. Participants completed the EQ-5D-5L general health utility instrument, the EQ vertical visual analogue scale (EQ-VAS) and the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25). Self-reported IRD diagnoses were classified as being associated with central or widespread retinal involvement. RESULTS: Responses from 647 participants aged 18-93 years were included, 50.1% were men and 77.6% had an IRD associated with widespread retinal involvement. The majority reported no problems with self-care and no pain/discomfort but did report anxiety/depression and problems with work, study, housework, or family/leisure activities. Most people with widespread involvement reported problems with mobility. Median EQ-5D-5L utility was 0.88 and 0.91 among people with widespread and central involvement, respectively (age and sex-adjusted p = 0.029); and median EQ-VAS was 75 and 80, respectively (adjusted p = 0.003). A moderate curvilinear correlation was observed between EQ-5D-5L and NEI-VFQ-25 composite score (Spearman's ρ 0.69), but not all people with poor vision-related quality of life had low EQ-5D-5L utility values. CONCLUSIONS: EQ-5D-5L health utility values are correlated with vision-related quality of life among adults with IRDs. However, the EQ-5D-5L may not be sensitive to the full impact of vision impairment on quality of life.

Diagnostic accuracy of self-reported age-related macular degeneration in the ASPREE Longitudinal Study of Older Persons.

BACKGROUND: The validity of findings from epidemiological studies using self-report of ophthalmic conditions depends on several factors. We assessed the diagnostic accuracy of self-reported age-related macular degeneration (AMD) among older Australians enroled in a primary prevention clinical trial and compared diagnostic accuracy between demographic subgroups. METHODS: At baseline (2010-2015), Australian sub-study participants of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, underwent bilateral two-field, 45° non-mydriatic colour retinal photography. Beckman classification of any-stage AMD was used as the reference standard diagnosis. Participants were asked whether a doctor had ever diagnosed them with "macular degeneration" (the index test) via a paper-based questionnaire as part of the ASPREE Longitudinal Study of Older Persons (ALSOP) within the first year of enrolment. RESULTS: In total, 4193 participants were included (aged 70-92 years, 50.8% female). Of those, 262 (6.3%) reported having AMD and 92 (2.2%) were unsure. Retinal grading detected 2592 (61.8%) with no AMD, 867 (20.7%) with early, 686 (16.4%) with intermediate and 48 (1.1%) with late AMD (n = 1601 with any-stage AMD, 38.2%). Self-reported AMD had 11.4% sensitivity (95% CI 9.9-13.1) and 96.9% specificity (95% CI 96.2-97.6) for any-stage AMD, with 69.8% and 63.9% positive and negative predictive values. Sensitivity was higher among participants with late-stage AMD (87.5%), older participants (26.8%), and those with poorer vision (41.0%). CONCLUSIONS: Although most participants with late-stage AMD were aware of having AMD, the majority with early and intermediate AMD were not. Therefore, findings from studies that rely on disease self-report should be interpreted with caution.

Clinical practice patterns for assessing children with learning difficulties: survey of eye health care professionals.

CLINICAL RELEVANCE: Understanding what aspects of vision or binocular vision may affect learning, and how these are assessed, is important for the eye health care professional assessing children with learning difficulties. It is vital that visual dysfunction is identified or excluded in these patients to ensure targeted and timely intervention. BACKGROUND: The aim of this study was to investigate similarities and differences between eye care professionals in the knowledge, attitudes and practice patterns, when evaluating children with learning difficulties. METHODS: This study was a cross-occupational, cross-sectional, predominantly quantitative internet-based survey. Ophthalmologists, optometrists, and orthoptists working in Australia were eligible to participate. A questionnaire comprising of 31 multiple-choice questions with up to 19 additional branching questions was distributed using REDCap in September 2022. RESULTS: A total of 130 responses were analysed (6 ophthalmologists, 84 orthoptists and 40 optometrists of whom 9 were practicing behavioural vision care). Most respondents assessed distance visual acuity (95%), near stereoacuity (85%), presence of strabismus (88%) and ocular movements (91%). Near vision was assessed less often (65%). Optometrists were most likely to measure colour vision (p < 0.002), accommodation and undertake a subjective refraction (each p < 0.001). Ophthalmologists were least likely to measure convergence (p = 0.041) but more likely to undertake a cycloplegic refraction (p = 0.044). More optometrists practicing behavioural vision care reported testing binocular vision (p = 0.026), fusional vergence (p < 0.001), saccades (p = 0.066), and smooth pursuit (p = 0.050) than other professions. There was a positive correlation between frequency and confidence level when assessing children with learning difficulties (ρ = 0.64). Respondents referred to paediatricians (39%), speech pathologists (30%), educational psychologists (29%) and general practitioners (29%). CONCLUSION: Despite similarities across occupations, there were differences in testing the vision and binocular functions of children with learning difficulties. Future research should aim to establish minimum standards for assessing this patient cohort to ensure consistent and relevant assessment.

Increased Glaucoma Case-finding Through Routine Optical Coherence Tomography in Optometry Practice.

OBJECTIVE: Timely detection of glaucoma is key to preventing or delaying vision loss. This study aimed to assess whether the routine use of optical coherence tomography (OCT) by optometrists for detection of glaucomatous changes in the optic nerve and retina increased glaucoma referrals to ophthalmologists. DESIGN: This study was a retrospective review of routinely-collected electronic medical records of patients from a chain of 331 optometry practices in Australia. PARTICIPANTS: Electronic medical records were reviewed for every patient aged 18-99 years who attended an included practice between January 1 and July 31, 2019. METHODS: Odds of referral for glaucoma assessment were compared between practices performing OCT routinely on all patients (OCT practices, n=175) and without OCT (non-OCT practices, n=20). A subset of referrals were assessed by ophthalmologists to determine the false positive referral rate. MAIN OUTCOME MEASURES: The primary outcome measure of this study was referral to an ophthalmologist for glaucoma assessment. A secondary outcome was the rate of false positive referrals, analysed in a subset of patients referred for glaucoma assessment. RESULTS: Records from 994,461 patients (59% female) were included and 10,475 (1.1%) were referred for glaucoma assessment. Most referrals were associated with normal intraocular pressure (non-OCT practices: n=496, 66%; OCT practices: n=6,603, 68%). Referral for glaucoma was higher in OCT practices (n=9,719, 1.1%) compared to non-OCT practices (n=756, 0.8%, age-, gender- and location-adjusted odds ratio 1.39, 95% confidence interval 1.10-1.76). Of 318 referred patients (3%, all from OCT practices) for whom ophthalmologist feedback was available, 68 (21%) were considered not to have glaucoma. CONCLUSIONS: The routine use of OCT in optometric practice may lead to more timely glaucoma detection and prevention of avoidable vision loss.

Quality of refractive error care in Pakistan: an unannounced standardised patient study.

OBJECTIVE: Undercorrected refractive errors are the primary cause of vision impairment worldwide, including in Pakistan. However, limited data exist on the quality of refractive error care. Our study assessed the quality of refractive error care in Punjab, Pakistan by estimating the proportion of spectacles that were optimally prescribed. METHODS AND ANALYSIS: In this cross-sectional study, 12 unannounced standardised patients (USPs) from Jhang, Khanewal and Sahiwal districts were recruited. USPs underwent baseline subjective refraction and were trained to attend optical services, observe consultations, request spectacles and obtain prescriptions. The spectacles received were compared with baseline refraction to determine quality. We also examined the associations between spectacle quality, service and patient characteristics. RESULTS: Out of 276 attempted visits to 69 optical services, 241 pairs of spectacles were dispensed. A population size-weighted percentage of 42.7% (95% CI 36.4% to 49.3%) of spectacles were optimal quality, with the range varying from 13.8% in Jhang to 67.0% in Khanewal. Half the suboptimal quality spectacles had horizontal prism deviations outside of tolerance limits. Optimal spectacles were associated with performing focimetry (unadjusted OR=7.15, 95% CI (3.02 to 16.94), p<0.001) and good communication (OR=2.23, 95% CI (1.06 to 4.67), p=0.03). Hyperopic USPs were less likely to receive optimal spectacles (OR=0.01 95% CI (0.00 to 0.11), p<0.001). CONCLUSION: The quality of refractive error care in Pakistan requires improvement, particularly in the Jhang district. Key areas for enhancing refractive error care in Pakistan include refining dispensing and refraction skills for hyperopic prescriptions, providing training on the risks of using previous spectacles, and emphasising the importance of effective communication skills.

Retinal imaging biomarkers of Alzheimer's disease: A systematic review and meta-analysis of studies using brain amyloid beta status for case definition.

Introduction: We performed a systematic review and meta-analysis of the association between retinal imaging parameters and Alzheimer's disease (AD). Methods: PubMed, EMBASE, and Scopus were systematically searched for prospective and observational studies. Included studies had AD case definition based on brain amyloid beta (Aß) status. Study quality assessment was performed. Random-effects meta-analyses of standardized mean difference, correlation, and diagnostic accuracy were conducted. Results: Thirty-eight studies were included. There was weak evidence of peripapillary retinal nerve fiber layer thinning on optical coherence tomography (OCT) (p = 0.14, 11 studies, n = 828), increased foveal avascular zone area on OCT-angiography (p = 0.18, four studies, n = 207), and reduced arteriole and venule vessel fractal dimension on fundus photography (p < 0.001 and p = 0.08, respectively, three studies, n = 297) among AD cases. Discussion: Retinal imaging parameters appear to be associated with AD. Small study sizes and heterogeneity in imaging methods and reporting make it difficult to determine utility of these changes as AD biomarkers. Highlights: We performed a systematic review on retinal imaging and Alzheimer's disease (AD).We only included studies in which cases were based on brain amyloid beta status.Several retinal biomarkers were associated with AD but clinical utility is uncertain.Studies should focus on biomarker-defined AD and use standardized imaging methods.

Self-rated eyesight among healthy older Australians: Baseline results of the ASPREE Longitudinal Study of Older Persons.

BACKGROUND: We aimed to describe the self-reported level of eyesight amongst a cohort of relatively healthy older Australian adults, and to investigate associations between poorer self-rated eyesight and demographic, health, and functional characteristics METHODS: The ASPirin in Reducing Events in the Elderly (ASPREE) Longitudinal Study of Older Persons (ALSOP) study was embedded in a multisite trial which recruited independently living Australians from general practices (2010-2014). Self-rated eyesight was recorded on a paper-based questionnaire as Excellent, Good, Fair, Poor, Very poor, or Completely blind at the baseline study wave RESULTS: Data from 14 592 participants (aged 70-95 years, 54.61% female) were included in this cross-sectional analysis. Eighty percent of participants reported excellent or good eyesight (n = 11 677). People with complete blindness were precluded from enrolling but 299 participants (2.0%) reported poor or very poor eyesight, and 2616 rated their eyesight as fair (17.9%). Lower levels of eyesight were associated with being older, female, fewer years of formal education, a primary language other than English, smoking, and self-reported macular degeneration, glaucoma, retinopathy, cataracts, and hearing problems (each p ≤ 0.021). People with lower levels of eyesight had a higher number of falls, frailty characteristics, and depressive symptoms, and lower mental and physical health functioning scores (each p < 0.001) CONCLUSIONS: Whilst most of these healthy older Australians reported good or excellent eyesight, a notable minority reported poor or very poor eyesight, and this was associated with a range of poorer health measures. These findings support the need for additional resources to prevent vision loss and associated sequelae.

Real-World Investigation of Impact of Retinal Fluid in Treatment Naïve Eyes Treated with Anti-VEGF for Neovascular Age-Related Macular Degeneration.

BACKGROUND: Traditionally, visual acuity gain and central retinal thickness have been used to measure outcomes when investigating the efficacy of vascular endothelial growth factor (VEGF) inhibitors for patients with neovascular age-related macular degeneration (nARMD). However, localization of retinal fluid may offer additional prognostic value for treatment. The primary aim of this retrospective clinical audit was to investigate whether the presence and location of subretinal fluid has an effect on the visual outcomes of treatment naïve patients with nARMD treated in the real-world setting with VEGF inhibitors. Secondary aims included investigation of change to visual and anatomical outcomes and investigation of the dosing schedule. METHODS: Retrospective observational study of patients attending one suburban and one regional ophthalmology clinic requiring treatment with VEGF inhibitors for nARMD using single-user non-identifiable data from the Fight Retinal Blindness! Registry from 2014 to 2020. Visual acuity (VA) and central subfield thickness (CST) were recorded at baseline, 3, 6, 12 and 24 months. RESULTS: Forty-nine eyes of 42 treatment naïve patients were included for analysis (aged 62-89 years). Almost half (49%) presented with a combination of intra- and subretinal fluid at baseline. Intraretinal fluid was present in 75% of eyes but decreased to 22.7% of eyes by 24 months. VA at baseline was 55 letters, and this improved by 6 letters. The change in VA from baseline to 3, 6 and 12 months was statistically significant (p < .05). The mean change in CST from baseline to 3 months was significant (-76 µm). This change was also observed at the other milestones (p < .001). CONCLUSIONS: The findings of this study suggest that allowing some subretinal fluid to remain will not affect treatment outcomes.

Interventions recommended for myopia prevention and control among children and adolescents in China: a systematic review.

In 2018, a consortium of government bodies in China led by the Ministry of Education released the Comprehensive Plan to Prevent Nearsightedness among Children and Teenagers (CPPNCT), aiming to reduce the incidence of myopia and control myopic progression in China. Recommendations span from home-based to school-based interventions, including time outdoors, physical activity, light exposure, near-work activity, screen time, Chinese eye exercises, diet and sleep. To date, the levels of evidence for this suite of interventions have not been thoroughly investigated. This review has summarised the evidence of the interventions recommended by the CPPNCT in myopia prevention and control. Thus, the following statements are supposed by the evidence: (1) Increasing time outdoors and reducing near-work time are effective in lowering incident myopia in school-aged children. (2) All interventions have a limited effect on myopia progression. Ongoing research may lead to a better understanding of the underlying mechanisms of myopia development, the interaction of different interventions and recommendations, confounding variables and their true effect on myopia prevention, and the identification of those most likely to respond to specific interventions. This field may also benefit from longer-term studies of the various interventions or strategies covered within this review article, to better understand the persistence of treatment effects over time and explore more novel approaches to myopia control.

The MOLES system to guide the management of melanocytic choroidal tumours: can optometrists apply it?

CLINICAL RELEVANCE: Although melanocytic choroidal tumours of the choroid are a common eye pathology, no standardised protocol exists for their management in the community. BACKGROUND: Choroidal naevi are found in approximately 6% of the adult White population, whereas choroidal melanomas are rare, with an annual incidence of 5-10/million/year. Multimodal imaging has advanced the understanding of malignancy imaging biomarkers, but distinguishing between a small melanoma and naevus remains difficult and an algorithm for their management by community practitioners has not been uniformly adopted. One of the authors (BD) devised the MOLES scoring system, which indicates malignancy likelihood according to mushroom shape, orange pigment, large size, enlargement, and subretinal fluid. When applied by ocular oncologists, the system accurately distinguishes choroidal naevi from melanomas. The aim of this study was to evaluate whether community optometrists can appropriately manage patients with melanocytic choroidal tumours using this system. METHODS: Clinical images of 25 melanocytic choroidal tumours were presented in an online survey, including colour fundus photographs, fundus autofluorescence, optical coherence tomography, and B-scan ultrasound images. Using the MOLES system, 39 optometrists diagnosed tumours as naevus or probable melanoma and decided between community monitoring and ophthalmologist referral. Responses were compared to MOLES grading of the same clinical images by ocular oncologists. RESULTS: Using MOLES, optometrists correctly identified 389/406 probable melanomas (95.8% sensitivity) and 331/516 choroidal naevi (64.1% specificity); correctly referred 773/778 tumours to an ophthalmologist (99.4% sensitivity); and correctly managed 80/144 lesions (55.6% specificity) in the community. CONCLUSION: Optometrists safely applied the MOLES scoring system in this survey. Further measures are indicated to reduce choroidal naevi over-referral and evaluate MOLES system usage in clinical optometric practice, where some imaging modalities may not be readily available.

Comparison of Photographic Screening Methods for Diabetic Retinopathy - A Meta-analysis.

INTRODUCTION: Diabetic Retinopathy (DR) is a leading cause of irreversible visual impairment and blindness in both developed and developing countries. Although the merits of DR screening are well recognized, significant variations in screening practices including imaging modality still exists. PURPOSE: To evaluate and compare the sensitivity and specificity of mydriatic and non-mydriatic photographic screening methods using 7-Field fundus photography or dilated fundus examination (DFE) by an ophthalmologist as reference standard. METHODS: A systematic review using PRISMA Guidelines was conducted by online search of MEDLINE, Web of Science, and other repositories of all available studies from 1990 until 2019. A total of 62 studies were included in the meta-analysis from a total of 406 suitable abstracts screened and 95 articles reviewed in full. Data were collected using a standardized extraction form independently, with all authors masked to others' search results. RESULTS: For the detection of any DR (ADR), sensitivity ranged from 81% with single field to a maximum of 99% for 4-7 fields and wide-angle images. For detection of referable DR (RDR) sensitivity ranged from 76% for single field to 93% for wide-angle photography. Specificity was lowest at 91% for wide-angle images and greatest at 99% for three field photography. Study heterogeneity was noted to be significant, which was partly attributed to the range of DR classification between studies. CONCLUSIONS: The sensitivity and specificity of DR screening are positively associated with number of photographic fields. Pooled estimates suggest non-mydriatic two-field photography may be sufficient for screening detection of ADR and RDR.

Is the disease risk and penetrance in Leber hereditary optic neuropathy actually low?

Pedigree analysis showed that a large proportion of Leber hereditary optic neuropathy (LHON) family members who carry a mitochondrial risk variant never lose vision. Mitochondrial haplotype appears to be a major factor influencing the risk of vision loss from LHON. Mitochondrial variants, including m.14484T>C and m.11778G>A, have been added to gene arrays, and thus many patients and research participants are tested for LHON mutations. Analysis of the UK Biobank and Australian cohort studies found more than 1 in 1,000 people in the general population carry either the m.14484T>C or the m.11778G>A LHON variant. None of the subset of carriers examined had visual acuity at 20/200 or worse, suggesting a very low penetrance of LHON. Haplogroup analysis of m.14484T>C carriers showed a high rate of haplogroup U subclades, previously shown to have low penetrance in pedigrees. Penetrance calculations of the general population are lower than pedigree calculations, most likely because of modifier genetic factors. This Matters Arising Response paper addresses the Watson et al. (2022) Matters Arising paper, published concurrently in The American Journal of Human Genetics.

Survey of perspectives of people with inherited retinal diseases on ocular gene therapy in Australia.

Many gene therapies are in development for treating people with inherited retinal diseases (IRD). We hypothesized that potential recipients of gene therapy would have knowledge gaps regarding treatment. We aimed to assess knowledge, attitudes, and perceptions of genetic therapies among potential recipients with IRD, using a novel instrument we designed (Attitudes to Gene Therapy-Eye (AGT-Eye)) and their associations with demographic data, self-reported visual status, and tools assessing quality of life and attitudes toward clinical trials using a community-based cross-sectional survey of Australian adults with IRD. AGT-Eye, overall quality of life EQ-5D-5L, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) and Patient Attitudes to Clinical Trials (PACT-22) instruments were administered. Six hundred and eighty-one people completed the study, 51.7% women of mean age 53.5 years (SD ± 15.8). Most participants (91.6%) indicated they would likely accept gene therapy if it was available to them or family members. However, only 28.3% agreed that they had good knowledge of gene therapy. Most obtained information about gene therapy from the internet (49.3%). Respondents with post-graduate degrees scored highest compared to other educational levels on methods (p < 0.001) and outcomes (p = 0.003) and were more likely to see economic value of treatment (p = 0.043). Knowledge gaps were present regarding methods and outcomes of gene therapy. This survey has shown high level of interest in the IRD community for gene therapies, and highlights areas for improved clinician and patient education.