Childhood Social Isolation as a Predictor of Retinal Neuronal Thickness in Middle Age: A Lifecourse Birth Cohort Study.

OBJECTIVE: We investigated whether childhood social isolation was associated with retinal neural layer changes in adulthood, and whether this association was independent of other childhood or adulthood risk factors, including adult social isolation. METHODS: Participants were members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal population-based birth cohort from Aotearoa New Zealand ( n = 1037), born 1972 to 1973 and followed until age 45 years, with 94% of the living cohort still participating. Social isolation was recorded prospectively at ages 5, 7, 9, and 11 years, from teacher and parent report. Retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer thicknesses were measured via optical coherence tomography at age 45 years. RESULTS: Childhood social isolation was associated with thinner average RNFL ( B = -0.739, p = .02), nasal RNFL ( B = -1.118, p = .005), and inferior RNFL ( B = -1.524, p = .007), although only nasal RNFL remained significant after adjustment. These associations were not fully explained by other psychosocial or physical health risk factors in childhood or adulthood, nor were they mediated by adult loneliness or social support. CONCLUSIONS: Childhood social isolation was an independent predictor of RNFL thickness in middle age. Highlighting prospective links between childhood psychosocial adversity and retinal neuronal measures will help to inform future research into the utility of retinal neuronal thickness as a biomarker for neurodegeneration.

Proof-of-concept calculations to determine the health-adjusted life-year trade-off between intravitreal anti-VEGF injections and transmission of COVID-19.

BACKGROUND: Clinical ophthalmological guidelines encourage the assessment of potential benefits and harms when deciding whether to perform elective ophthalmology procedures during the COVID-19 pandemic, in order to minimize the risk of disease transmission. METHOD: We performed probability calculations to estimate COVID-19 infection status and likelihood of disease transmission among neovascular age-related macular degeneration patients and health-care workers during anti-VEGF procedures, at various community prevalence levels of COVID-19. We then applied the expected burden of COVID-19 illness and death expressed through health-adjusted life-years (HALYs) lost. We compared these results to the expected disease burden of severe visual impairment if sight protecting anti-VEGF injections were not performed. RESULTS: Our calculations suggest a wide range of contexts where the benefits of treatment to prevent progression to severe visual impairment or blindness are greater than the expected harms to the patient and immediate health care team due to COVID-19. For example, with appropriate protective equipment the benefits of treatment outweigh harms when the chance of progression to severe visual impairment is >0.044% for all scenarios where COVID-19 prevalence was 1/1000, even when the attack rate in the clinical setting is very high (5-43%). CONCLUSION: Unless COVID-19 prevalence is very high, the reduced disease burden from avoiding visual impairment outweighs the expected HALYs lost from COVID-19 transmission. This finding is driven by the fact that HALYs lost when someone suffers severe visual impairment for 5 years are equivalent to nearly 400 moderate cases of infectious disease lasting 2 weeks each.

Diabetic retinopathy screening using deep neural network.

IMPORTANCE: There is a burgeoning interest in the use of deep neural network in diabetic retinal screening. BACKGROUND: To determine whether a deep neural network could satisfactorily detect diabetic retinopathy that requires referral to an ophthalmologist from a local diabetic retinal screening programme and an international database. DESIGN: Retrospective audit. PARTICIPANTS: Diabetic retinal photos from Otago database photographed during October 2016 (485 photos), and 1200 photos from Messidor international database. METHODS: Receiver operating characteristic curve to illustrate the ability of a deep neural network to identify referable diabetic retinopathy (moderate or worse diabetic retinopathy or exudates within one disc diameter of the fovea). MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve, sensitivity and specificity. RESULTS: For detecting referable diabetic retinopathy, the deep neural network had an area under receiver operating characteristic curve of 0.901 (95% confidence interval 0.807-0.995), with 84.6% sensitivity and 79.7% specificity for Otago and 0.980 (95% confidence interval 0.973-0.986), with 96.0% sensitivity and 90.0% specificity for Messidor. CONCLUSIONS AND RELEVANCE: This study has shown that a deep neural network can detect referable diabetic retinopathy with sensitivities and specificities close to or better than 80% from both an international and a domestic (New Zealand) database. We believe that deep neural networks can be integrated into community screening once they can successfully detect both diabetic retinopathy and diabetic macular oedema.

Does amblyopia have a functional impact? Findings from the Dunedin Multidisciplinary Health and Development Study.

BACKGROUND: Existing data on the functional impact of amblyopia are conflicting. The functional impact of amblyopia is a critical component of the viability and effectiveness of childhood vision screening programmes and treatment regimes. DESIGN: Prospective longitudinal birth cohort (the Dunedin Multidisciplinary Health and Development Study). PARTICIPANTS: One thousand thirty-seven children born in Dunedin, New Zealand, between April 1972 and March 1973, assessed from ages 3 to 32 years. METHODS: Comparison of study members with no amblyopia, recovered amblyopia, possible amblyopia or amblyopia according to both classic (6/12 visual acuity or worse in at least one eye, or a two-line or greater differential between the visual acuity in both eyes) and modern (6/9 visual acuity or worse in at least one eye) definitions of amblyopia. MAIN OUTCOME MEASURES: Childhood motor development, teenage self-esteem and adult socioeconomic status (assessed by occupation, education, reading ability and income). RESULTS: There was no evidence of poorer motor development, lower self-esteem or reduced adult socioeconomic status in study members with amblyopia or recovered amblyopia when compared with those with no amblyopia. CONCLUSIONS: Amblyopia or having recovered amblyopia does not functionally impact on childhood motor development, teenage self-esteem or adult socioeconomic status within this cohort. The wide range of visual deficits and adaptations that are known to occur in amblyopic vision do not translate into important 'real life' outcomes for the study members with amblyopia or recovered amblyopia. The age-related cumulative lifetime risk of bilateral visual impairment in amblyopia will be assessed in future studies.

Are macular drusen in midlife a marker of accelerated biological ageing?

CLINICAL RELEVANCE: Macular drusen are associated with age-related maculopathy but are not an ocular manifestation or biomarker of systemic ageing. BACKGROUND: Macular drusen are the first sign of age-related maculopathy, an eye disease for which age is the strongest risk factor. The aim of this cohort study was to investigate whether macular drusen in midlife - a sign of the earliest stages of age-related macular degeneration (AMD) - are associated with accelerated biological ageing more generally. METHODS: Members of the long-running Dunedin Multidisciplinary Health and Development Study (hereafter the Dunedin Study, n = 1037) underwent retinal photography at their most recent assessment at the age of 45 years. Images were graded for the presence of AMD using a simplified scale from the Age-Related Eye Disease Study (AREDS). Accelerated ageing was assessed by (i) a measure of Pace of Ageing defined from a combination of clinical and serum biomarkers obtained at ages 26, 32, 38, and 45 years and (ii) Facial Ageing, defined from photographs obtained at age 38 and 45 years. RESULTS: Of the 938 participants who participated at the age 45 assessments, 834 had gradable retinal photographs, and of these 165 (19.8%) had macular drusen. There was no significant difference in Pace of Ageing (p = .743) or Facial Ageing (p = .945) among participants with and without macular drusen. CONCLUSIONS: In this representative general population sample, macular drusen in midlife were not associated with accelerated ageing. Future studies tracking longitudinal changes in drusen number and severity at older ages may reveal whether drusen are a biomarker of accelerated ageing.

Associations Between Thinner Retinal Neuronal Layers and Suboptimal Brain Structural Integrity in a Middle-Aged Cohort.

Purpose: The retina has potential as a biomarker of brain health and Alzheimer's disease (AD) because it is the only part of the central nervous system which can be easily imaged and has advantages over brain imaging technologies. Few studies have compared retinal and brain measurements in a middle-aged sample. The objective of our study was to investigate whether retinal neuronal measurements were associated with structural brain measurements in a middle-aged population-based cohort. Participants and Methods: Participants were members of the Dunedin Multidisciplinary Health and Development Study (n=1037; a longitudinal cohort followed from birth and at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and most recently at age 45, when 94% of the living Study members participated). Retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were measured by optical coherence tomography (OCT). Brain age gap estimate (brainAGE), cortical surface area, cortical thickness, subcortical grey matter volumes, white matter hyperintensities, were measured by magnetic resonance imaging (MRI). Results: Participants with both MRI and OCT data were included in the analysis (RNFL n=828, female n=413 [49.9%], male n=415 [50.1%]; GC-IPL n=825, female n=413 [50.1%], male n=412 [49.9%]). Thinner retinal neuronal layers were associated with older brain age, smaller cortical surface area, thinner average cortex, smaller subcortical grey matter volumes, and increased volume of white matter hyperintensities. Conclusion: These findings provide evidence that the retinal neuronal layers reflect differences in midlife structural brain integrity consistent with increased risk for later AD, supporting the proposition that the retina may be an early biomarker of brain health.

Roadmap for an imaging and modelling paediatric study in rural NZ.

Our study methodology is motivated from three disparate needs: one, imaging studies have existed in silo and study organs but not across organ systems; two, there are gaps in our understanding of paediatric structure and function; three, lack of representative data in New Zealand. Our research aims to address these issues in part, through the combination of magnetic resonance imaging, advanced image processing algorithms and computational modelling. Our study demonstrated the need to take an organ-system approach and scan multiple organs on the same child. We have pilot tested an imaging protocol to be minimally disruptive to the children and demonstrated state-of-the-art image processing and personalized computational models using the imaging data. Our imaging protocol spans brain, lungs, heart, muscle, bones, abdominal and vascular systems. Our initial set of results demonstrated child-specific measurements on one dataset. This work is novel and interesting as we have run multiple computational physiology workflows to generate personalized computational models. Our proposed work is the first step towards achieving the integration of imaging and modelling improving our understanding of the human body in paediatric health and disease.

Associations Between Retinal Nerve Fiber Layer and Ganglion Cell Layer in Middle Age and Cognition From Childhood to Adulthood.

IMPORTANCE: The retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) have been proposed as potential biomarkers for Alzheimer disease (AD). Although a number of studies have shown that knowing the thickness of RNFL and GCL can help differentiate between patients with AD and healthy controls, it is unclear whether these associations are observable earlier in life. OBJECTIVE: To examine whether RNFL and GCL thickness was associated with global cognitive performance in middle age and in childhood and with a decline in cognitive performance from childhood to adulthood and whether RNFL and GCL thickness was associated with decline in specific cognitive domains over the same period. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cohort study involved members of the Dunedin Multidisciplinary Health and Development Study, a longitudinal representative birth cohort from New Zealand (n = 1037). Participants were born in 1972 to 1973 and followed up until age 45 years, with 94% of the living cohort still participating. MAIN OUTCOMES AND MEASURES: Cognitive performance (Full Scale IQ, processing speed, perceptual reasoning, and verbal comprehension) measured at ages 7, 9, and 11 years (mean value) and age 45 years, and RNFL and GCL thickness measured via optical coherence tomography (OCT) at age 45 years. RESULTS: Data were analyzed between August 2020 and April 2021. Data from 865 participants were included in the present study (50.2% male, 49.8% female; 92.2% of the 938 study members seen at age 45 years). Of the 73 participants who were excluded, 63 were excluded because of issues with OCT scans and 10 were excluded because of diseases affecting the retina. Thinner RNFL and GCL were associated with lower Full Scale IQ in childhood and at age 45 years. Thinner RNFL was also associated with a greater decline in processing speed from childhood to adulthood. CONCLUSIONS AND RELEVANCE: RNFL and GCL thickness in middle age was associated with cognitive performance in childhood and adulthood, and thinner RNFL with a decline in processing speed between childhood and adulthood. These data emphasize the potential utility of OCT measures as biomarkers of cognitive function; however, further longitudinal studies are needed to determine whether retinal thinning precedes cognitive decline and whether other confounding factors may account for this association.

Impact of the COVID-19 pandemic lockdown on public sector ophthalmic work by New Zealand's ophthalmologists.

AIM: In response to the COVID-19 pandemic, the New Zealand government enforced a nationwide 'alert level 4' lockdown from 26 March to 27 April 2020. We assessed the impact of this lockdown on New Zealand's public ophthalmology service. METHOD: An anonymous online survey was sent to all New Zealand-based fellows of the Royal Australian and New Zealand College of Ophthalmologists (RANZCO) after lockdown. Respondents provided retrospective assessment of practice patterns and their personal health during the COVID-19 lockdown. This was supported by national-level administrative data, allowing survey findings to be contextualised. RESULTS: Fifty-seven respondents (response rate 49%) working in the public health system participated. A large majority of respondents reduced elective clinic and surgical volumes by at least 75% (82% and 98%, respectively). National-level information confirmed clinic reduced to 38.2% of normal and elective operating volumes to 11.5%, with virtual visits increasing 17.9-fold. Elective clinic and elective operating volumes promptly recovered to usual volumes on the second month post lockdown. Most respondents (58%) followed the RANZCO triaging guideline, and 28% triaged emergencies only. At a personal level, respondents reported a significant physical health benefit (p<0.001) associated with the lockdown experience, but no change in mental health or social wellbeing. CONCLUSIONS: Publicly employed ophthalmologists experienced dramatic reductions to elective clinic and operating volumes during the COVID-19 lockdown. The prompt recovery of service delivery volumes back to pre-lockdown levels supports the value of a COVID-19 elimination strategy in New Zealand. Virtual visits for selected patients allowed ongoing management without risking virus transmission.

Association of History of Psychopathology With Accelerated Aging at Midlife.

Importance: Individuals with mental disorders are at an elevated risk of developing chronic age-related physical diseases. However, it is not clear whether psychopathology is also associated with processes of accelerated aging that precede the onset of age-related disease. Objective: To test the hypothesis that a history of psychopathology is associated with indicators of accelerated aging at midlife. Design, Setting, and Participants: This prospective cohort study was based on the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort of 1037 individuals born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand. Members were followed up to age 45 years (until April 2019). Data were analyzed from January 6 to December 7, 2020. Exposures: Mental disorders were assessed in 6 diagnostic assessments from ages 18 to 45 years and transformed through confirmatory factor analysis into continuous measures of general psychopathology (p-factor) and dimensions of internalizing, externalizing, and thought disorders (all standardized to a mean [SD] of 100 [15]). Main Outcomes and Measures: Signs of aging (biological pace of aging; declines in sensory, motor, and cognitive functioning; and facial age) were assessed up to age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports. Results: Of the original 1037 cohort participants, 997 were still alive at age 45 years, of whom 938 (94%) were assessed (474 men [50.5%]). Participants who had experienced more psychopathology exhibited a faster pace of biological aging (ß, 0.27; 95% CI, 0.21-0.33; P < .01); experienced more difficulties with hearing (ß, 0.18; 95% CI, 0.12-0.24; P < .01), vision (ß, 0.08; 95% CI, 0.01-0.14; P < .05), balance (ß, 0.20; 95% CI, 0.14-0.26; P < .01), and motor functioning (ß, 0.19; 95% CI, 0.12-0.25; P < .01); experienced more cognitive difficulties (ß, 0.24; 95% CI, 0.18-0.31; P < .01); and were rated as looking older (ß, 0.20; 95% CI, 0.14-0.26; P < .01). Associations persisted after controlling for sex, childhood health indicators, maltreatment, and socioeconomic status and after taking into account being overweight, smoking, use of antipsychotic medication, and the presence of physical disease. Tests of diagnostic specificity revealed that associations were generalizable across externalizing, internalizing, and thought disorders. Conclusions and Relevance: In this cohort study, a history of psychopathology was associated with accelerated aging at midlife, years before the typical onset of age-related diseases. This link is not specific to any particular disorder family but generalizes across disorders. Prevention of psychopathology and monitoring of individuals with mental disorders for signs of accelerated aging may have the potential to reduce health inequalities and extend healthy lives.

Characterising the ocular surface and tear film in a population-based birth cohort of 45-year old New Zealand men and women.

PURPOSE: To assess the prevalence of dry eye disease, aqueous tear deficiency, meibomian gland dysfunction, and asymptomatic ocular surface disease in a population-based cohort of 45-year-old New Zealand men and women. METHODS: This cross-sectional study of 885 participants (442 females, 443 males) was based on a population-representative birth cohort of individuals born between April 1 1972 and March 31 1973 in Dunedin, New Zealand (the Dunedin Multidisciplinary Health and Developmental Study). Participants were assessed at 45 years of age, and dry eye symptomology, ocular surface characteristics, and tear film quality were evaluated for each participant within a single clinical session. The diagnosis of dry eye disease was made according to the validated rapid non-invasive dry eye assessment algorithm. RESULTS: Clinical dry eye signs were present in 402 (45%) participants, of which 78 (9%) participants fulfilled the diagnostic criteria for dry eye disease, and 322 (37%) had asymptomatic ocular surface disease. Among participants with dry eye disease, 22 (2%) exhibited aqueous tear deficiency, and 65 (7%) had meibomian gland dysfunction. Females were more likely to be affected by dry eye disease, meibomian gland dysfunction, and asymptomatic ocular surface disease (all p < 0.05). CONCLUSIONS: Clinical dry eye signs were present in almost half of this population-based cohort of 45-year-old New Zealanders, although only 9% of participants fulfilled the diagnostic criteria for dry eye disease. The high prevalence of asymptomatic ocular surface disease presents an opportunity for preventative public health intervention.

Blinking Sam: the ocular afflictions of Dr. Samuel Johnson.

The poor health of Samuel Johnson (1709-1784) has fascinated the public for more than 200 years. The illnesses of few famous men, with the possible exception of Napoleon, have attracted more speculation. Johnson was an outstanding 18th-century literary figure, an essayist, novelist, and poet, and is particularly famous as the creator of the first important dictionary of the English language. His writings and those of his physicians and friends, particularly his biographer, James Boswell, provide an intimate account of a cultural icon.

The big brown eyes of Samuel Pepys.

Samuel Pepys (1633-1703) is known for writing the finest diary in the English language. He was a man of remarkable accomplishments who transformed the English Navy, was president of the Royal Society, and was a member of the British Parliament. He survived the Great Plague and imprisonment in the Tower of London. During the years when he was writing the diary, Pepys began to experience great pain in his eyes when reading and writing and from photophobia, which caused him to give up writing the diary. Pepys also had an ultimately unjustifiable fear of blindness.