Loneliness and mental wellbeing in people with inherited macular disease

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Crossland, Marc S. Tibber, Lottie A.G. Wood, Rachael F. Canavan, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7917603/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Purpose: People with vision impairment have lower mental wellbeing than people without eye disease. Loneliness is thought to be associated with lower wellbeing in this population, but the confounding effect of mental ill-health and other factors which affect wellbeing has not been addressed. Here, we explored associations between loneliness and wellbeing in people with inherited macular disease, controlling for mental ill-health, demographic and clinical factors. Methods: Thirty-six people with inherited macular disease were recruited. Age, visual acuity, duration of disease and socioeconomic status were extracted from hospital notes. Loneliness, depression, anxiety and mental wellbeing were assessed using self-report questionnaires. Wellbeing was compared to a reference population of adults in the United Kingdom. Univariate and stepwise multivariate regression was used to examine the association between loneliness and wellbeing, controlling for demographic, clinical and mental health factors. Results: On average, participants’ wellbeing was not significantly different to the reference population (this study: mean: 50.9, sd: 9.68; reference population; mean=51.4; sd: 9.42; ANOVA, F = 0.099, p = 0.75). Univariate linear regression showed significant associations between wellbeing and loneliness ( b = -38.7; 95%CI -57, -20; p < 0.0001), depression ( b = -6.67; 95%CI -10, -2.9; p < 0.0001) and anxiety ( b = -5.37; 95%CI -8.7, 2.0; p < 0.0001). None of the other demographic and clinical variables were related to wellbeing at the p = 0.05 level. Stepwise regression revealed loneliness, gender, depression and anxiety to be (together) significantly associated with wellbeing, accounting for 61% of the variance in wellbeing ( r 2 = 0.613). Conclusions: Loneliness was associated with lower mental wellbeing even after controlling for mental ill-health, demographic and clinical factors. The severity of vision loss can not be taken as a simple index of likely wellbeing. Interventions which target loneliness may help maximise wellbeing in people with inherited macular disease. loneliness low vision macula inherited vision impairment wellbeing Key Points Mental wellbeing for our participants with inherited macular disease, who had access to low vision clinics and other support services, was similar to the general population; Participants reporting higher levels of loneliness had lower levels of mental wellbeing than those who were less lonely; This relationship persisted after controlling for mental ill-health, demographic or disease factors which could affect wellbeing. INTRODUCTION Mental wellbeing is reduced in people with vision impairment,[ 1 , 2 ] but the reasons for this are not fully understood. Previous research has identified a variety of factors associated with poorer wellbeing in this population, including loneliness, lower social support, lower self-efficacy, unemployment and having a later onset of vision impairment.[ 3 ] Loneliness is strongly associated with reduced wellbeing, depression, anxiety, mental ill-health, poor physical health and increased mortality in the general population.[ 4 – 6 ] On average, people with vision impairment report higher levels of loneliness [ 7 – 10 ] and this is associated with lower life satisfaction [ 7 ] and depression.[ 9 ] Loneliness appears to be more likely in adults with vision impairment who live alone, who have limited mobility, who are not working or studying and who do not describe themselves as religious.[ 7 , 10 ] This suggests loneliness is not a direct consequence of eye disease, but rather an indirect effect of the isolation and activity limitation which can be associated with vision impairment. As well as having lower wellbeing, people with vision impairment are far more likely to experience depression [ 11 ] and anxiety [ 12 ] than their peers without sight loss. Although mental wellbeing is a broader concept than just the absence of mental ill-health, wellbeing is generally lower in people with depression or anxiety, which may confound previous research showing a relationship between loneliness and wellbeing in people with vision impairment. To date, most research on wellbeing in people with eye disease has investigated older adults, with studies typically combining different causes of vision impairment, including (in some cases) cerebral vision impairment and syndromic conditions. However, different diseases may impact wellbeing in different ways. For example, the psychological impact of lifelong cerebral visual impairment is likely to be very different to having peripheral vision loss from glaucoma in later life, or central vision loss from inherited macular disease as a teenager. The wellbeing of adolescents with vision impairment is largely unexplored. In this paper we explore the relationship between loneliness and mental wellbeing in a group of adolescents and adults with a single, non-syndromic, ocular cause of vision impairment: inherited macular disease. We control for demographic and socioeconomic (age, sex, ethnic origin, socioeconomic status), clinical (visual acuity, duration of disease) and mental health (depression and anxiety) variables, all of which are known to affect wellbeing. We hypothesised that mental wellbeing would be lower in people with vision impairment who have higher levels of loneliness, even after controlling for these covariates. METHODS Study design This was a cross-sectional observational study evaluating the wellbeing of people with vision impairment caused by inherited macular disease. Patient and public involvement and engagement The study was developed in collaboration with people with lived experience of vision impairment and their families, including representatives from the Stargardt’s Connected charity and the Moorfields Eye-Young Persons’ Advisory Group, who also reviewed the participant information documents. One of the participants was asked to provide feedback on an early draft of this manuscript and evaluate the study with particular reference to the accessibility and ease of engagement in the study; their satisfaction with their participation in the study; and their comments on the clarity of the manuscript. Participants People aged 13 years or older attending genetic eye disease or low vision clinics at Moorfields Eye Hospital who had a diagnosis of inherited macular disease were invited to participate. As assessed by the study team, those who did not have sufficient English language skills to complete the assessments, or who had hearing loss that affected their ability to complete telephone assessments, were excluded. Data collection Demographic details including age, sex and ethnicity were extracted from hospital records, as were relevant medical details (type of inherited macular disease, time of diagnosis, time of symptom onset, visual acuity in the better eye). Age was categorised as adolescent (13–18 years), emerging adult (18–29 years), adult (30–64 years) and older adult (> 64 years). Visual acuity was categorised as mild, moderate, severe or blind, in line with ICD-11 guidelines [ 13 ]. Participants’ home postcode using the 2019 English indices of deprivation, which links socioeconomic status to residents’ lower-layer super output area (a region of approximately 400–1200 households, or 1000–3000 people) was used as a proxy for socioeconomic status.[ 14 ] Loneliness, depression, anxiety and mental wellbeing were measured during a single telephone call between each participant and a member of the study team, at a time of the participant’s choosing. Loneliness was measured using the UCLA loneliness scale version 3 [ 15 ] for adolescents (aged 13–17 years), and the revised UCLA loneliness scale [ 16 ] for those over 18 years. These instruments comprise 20 items, have 4 response levels, and have high internal consistency, construct validity and test-retest correlation. Higher values on these scales relate to greater loneliness. Depression was measured using the 25-item (4-response level) Revised Children’s Anxiety and Depression Scale (RCADS-25 [ 17 ]) in adolescents, and the 9-item, 4-response level, Patient Health Questionnaire 9 (PHQ-9 [ 18 ]) in adults. Anxiety was measured using the RCADS-25 in adolescents and the Generalized Anxiety Disorder-7 (GAD-7 [ 19 ]) 7-item, 4-response level instrument in adults. Mental wellbeing was measured with the Warwick Edinburgh Mental Wellbeing Scale (WEMWS) for all participants. [ 20 ] On this scale, higher values correspond to more anxiety, depression, and better wellbeing, respectively. All have been well validated and show robust psychometric properties.[ 18 – 20 ] At the end of the data collection session, participants were offered referral to age-appropriate counselling services. A suicide and self-harm risk assessment protocol was in place, developed by a senior clinical psychologist (author MST). All members of the research team were offered clinical supervision and had access to confidential counselling services. Statistical design Data were collected using the secure Research Electronic Data Capture (REDCap) system hosted by University College London and stored in a secure database. All data were tested for normality using the Shapiro Wilk test, with log transformations being performed where data departed from normality at the p < 0.05 level. Analysis of variance (ANOVA) was used to compare wellbeing values to benchmark data from the Health Survey for England.[ 21 ] Descriptive statistics were used to identify caseness for depression and anxiety for included participants. Caseness is a term widely used in psychiatry, which refers to meeting the diagnostic threshold for a disorder. RCADS-25 data were converted to T-scores, normalised by age and gender, for depression and anxiety, based on Ebesutani’s dataset.[ 22 ] T-scores < 65 were defined as in the ‘normal range,’ between 65 and 69 as in the ‘borderline clinical range,’ and of 70 and above as in the ‘clinical range.’ For adults, following clinical recommendations, caseness for depression and anxiety were defined as scores of ≥ 10 on the PHQ-9[ 18 ] and GAD-7[ 19 ], respectively. This allowed for comparison between adolescents and adults. To explore the relationship between wellbeing and loneliness, several linear regression analyses were performed. First, a series of univariate regression analyses were undertaken, regressing wellbeing (separately) on loneliness and covariates including demographic (age, gender, ethnic origin, socioeconomic status), clinical (visual acuity, duration of disease), and mental health (caseness for depression and anxiety) variables to explore basic patterns of association. Next, two additional models were run, using forward stepwise multivariate regression. In the first, wellbeing was regressed on loneliness, with demographic and clinical variables assessed for inclusion; in the second, the same model was run, with mental health variables also assessed for inclusion. Analyses were performed in JMP Pro (v. 18.2.2, JMP Statistical Discovery LLC, Cary, North Carolina, USA). RESULTS Thirty-six participants were recruited. Participants’ demographic, socioeconomic, clinical and mental health characteristics are shown in Table 1 . Duration of disease and loneliness data were positively skewed and were log transformed. Table 1 Participant demographics and clinical characteristics. IMD: inherited macular disease. Number (%) Age group Adolescent 9 (25%) Emerging adult 6 (17%) Adult 16 (44%) Older adult 5 (24%) Gender Female 17 (47%) Male 19 (53%) Ethnic group Asian or Asian British 13 (36%) Mixed or multiple ethnic groups 6 (17%) White 13 (36%) Not stated 4 (11%) Socioeconomic status (decile) 1 (most deprived) 7 (21%) 2 2 (6%) 3 2 (6%) 4 1 (3%) 5 4 (12%) 6 4 (12%) 7 6 (12%) 8 4 (12%) 9 3 (9%) 10 (least deprived) 1 (3%) Missing data 2 (6%) Disease ABCA4/Stargardt 20 (56%) Best disease 3 (8%) Other IMD 9 (25%) Genetically Unconfirmed 4 (11%) Vision impairment category Not vision impaired 2 (5.6%) Mild 7 (19%) Moderate 17 (47%) Severe 7 (19%) Blind 5 (14%) Anxiety Caseness Yes 9 (25%) No 27 (75%) Depression Caseness Yes 6 (17%) No 30 (83%) Median (IQR) Duration of disease Years 11 (25) Loneliness UCLA scale 31 (15) The mean wellbeing score, measured on the WEMWS, was 50.9 (sd: 9.7). On average, participants’ wellbeing was not significantly different to that of the general population (general population; mean = 51.4; sd: 9.42; this study: mean: 50.9, sd: 9.68; ANOVA, F = 0.099, p = 0.75). Ten of our participants had ‘moderate’ levels of loneliness and five had ‘moderate/high’ loneliness. Univariate linear regression showed a significant linear association between wellbeing and loneliness ( r 2 = 0.35, p < 0.001). With respect to other variables explored, wellbeing was significantly associated with depression ( r 2 = 0.27, p < 0.01) and anxiety ( r 2 = 0.24, p 0.05). Loneliness was not correlated with having depression ( χ 2 = 0.0023, p = 0.96) or anxiety ( χ 2 = 1.13, p = 0.29). In the first stepwise regression (in which demographic, socioeconomic and clinical variables were added), the association between wellbeing and loneliness remained significant ( r 2 = 0.31, p < 0.01) and gender was retained ( r 2 = 0.43, p < 0.05); overall, the model accounted 47% of the variance in wellbeing ( r 2 = 0.474). In the second stepwise regression model (in which anxiety and depression were also added), the association between wellbeing remained significant ( r 2 = 0.27, p < 0.01) and gender, depression and anxiety were retained; overall, the model accounted for 61% of the variance in wellbeing ( r 2 = 0.613). Table 2 Results of univariate and multivariate regression analyses of wellbeing. UCLA: University of California Los Angeles loneliness scale. CI: confidence interval. Univariate models Multivariate model with demographic and clinical variables Multivariate model with demographic, clinical and mental ill-health variables Coefficient (95% CI) Coefficient (95% CI) Coefficient (95% CI) Loneliness (log UCLA score) -38.7 (-57, -20) p < 0.001 -37.2 (-54, -20) p < 0.001 -35.7 (-51, -20) p < 0.0001 Age group (adolescent) 2.30 (-0.88, 5.48) p = 0.15 - - Gender (female) 2.85 (-0.21, 5.9) p = 0.08 -3.18 (-5.5, -0.83) p < 0.01 -1.83 (-4.1, 0.47) p = 0.12 Ethnic group (white British) -2.07 (-5.54, 1.40) p = 0.25 - - Socioeconomic status (least deprived) -0.25 (-1.45, 0.95) p = 0.68 - - Vision impairment level (none) -0.15 (-3.37, 3.08) p = 0.73 - - Duration of disease (log years) -2.39 (-9.2, 4.5) p = 0.50 - - Depression -6.67 (-10, -2.9) p < 0.01 - -3.76 (-7.3, -0.26) p < 0.05 Anxiety -5.37 (-8.7, 2.0) p < 0.01 - -2.05 (-4.8, 0.67) p = 0.14 Participant review The participant confirmed that the study asked an important research question, used appropriate methods and recruited an appropriate population. He did not experience any accessibility problems with the study and did not find any of the questions asked ambiguous. He made some comments on the readability of the manuscript (specifically, the use of acronyms), which have been incorporated. DISCUSSION As hypothesised, we found an association between loneliness and mental wellbeing in adolescents and adults with inherited eye disease, with people who reporting higher levels of loneliness also reporting lower levels of wellbeing. This supports the findings of other research linking loneliness to wellbeing in eye disease [ 7 – 10 ] and extends these findings by showing that this relationship remained significant after controlling for demographic, socioeconomic, clinical and mental health variables. Depression and anxiety were also associated with lower levels of wellbeing, but demographic and clinical factors were not. Levels of wellbeing experienced by our participants were broadly similar to the general population. The discrepancy between this finding and previous work, which showed lower levels of wellbeing in people with vision impairment relative to the general population, [ 1 – 3 ] might be due to our participants being recruited from a specialist ophthalmology centre, where they had access to low vision assessment, counselling, emotional and genetic counselling, eye clinic liaison officers and expert ophthalmology care. Thus, participation biases may have excluded those with the lowest levels of wellbeing. Low mental wellbeing is known to be a risk factor for the development of major depression.[ 23 ] Encouragingly, the most significant predictor of reduced wellbeing which we identified – loneliness - appears to be potentially modifiable, for example, by social prescribing [ 24 ] and mentoring programmes.[ 25 ] A particularly encouraging finding of our work is that there was no association between wellbeing and nonmodifiable risk factors, such as age, ethnicity, disease severity and disease duration. The severity of vision loss can not be taken as a simple index of wellbeing or mental ill-health risk; instead the relationship between eye disease and wellbeing is likely to be more complex and dependent on multiple social and environmental factors. Unlike Verstraten and colleagues,[ 9 ] who measured loneliness and depression in a cohort of older adults, we did not find a relationship between depression and loneliness. The reason for this apparent discrepancy is unclear, though the lower and broader age distribution of our sample is one possibility. For example, the effects of loneliness may be elevated in older populations, who commonly experience greater levels of social isolation.[ 26 , 27 ] Would depression and loneliness affect wellbeing to the same extent in people without vision impairment? Perhaps, but as depression [ 11 ] and loneliness [ 7 , 9 ] are both higher in people with vision impairment, we believe that the impact of these factors on wellbeing in this population is particularly important. Interventions to target loneliness (such as social prescribing, support groups and befriending services) and depression (such as counselling and prompt referral to mental health services) should be tailored and offered to people with vision impairment and evaluated empirically. Limitations One limitation of our study is its relatively small sample size, largely caused by the relative rarity of inherited macular disease. A further limitation was that our study was cross-sectional in nature, so we were are unable to infer causation, or the underlying direction thereof. However, we are in the process of collecting longitudinal data from the adolescent participants in this study. As discussed above, our participants may not be fully representative of the general population with inherited macular disease. People with vision impairment who are medically excluded, or those who do not have access to a specialist centre with such a comprehensive support service, may have lower wellbeing when compared to people included in this study. All of our participants had ‘low,’ ‘moderate’ or ‘moderate/high’ levels of loneliness, with none having the highest level of loneliness as measured on the UCLA scale. Additionally, all of our participants received services through the National Health Service, free of charge at the point of delivery, which may limit the applicability of our results to non-European settings. Although we did not find an impact of socioeconomic status on mental health, people from areas of higher social deprivation are less likely to access eyecare [ 28 ] and may be less likely to have been recruited for the present study. Further, our method of using an area level proxy for socioeconomic status is a relatively unreliable method. Conclusions We found loneliness to be strongly associated with reduced wellbeing in a group of adolescents and adults with vision impairment caused by inherited macular disease. Disease factors such as the severity of vision loss can not be used as a proxy or a predictor of likely wellbeing. The role of interventions which support loneliness, such as social prescribing and mentoring, should be explored for people with vision impairment. Abbreviations ANOVA analyses of variance GAD-7 Generalized Anxiety Disorder-7 instrument IMD inherited macular disease PHQ-9 Patient Health Questionnaire-9 RCADS-25 25-item Revised Children’s Anxiety and Depression Scale REDCap Research Electronic Data Capture WEMWS Warwick Edinburgh Mental Wellbeing Scale Declarations Ethics approval and consent to participate The study was performed in accordance with the Declaration of Helsinki and received ethical approval from the Health Research Authority (IRAS number 326182) following review by the London - City & East Research Ethics Committee. All adult participants gave informed consent before data collection. Participants under the age of 18 assented to taking part in the study and informed consent was obtained from a parent or carer. Consent for publication Not applicable Conflict of interest disclosure The authors declare that they have no competing interests. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This work was funded by a project grant from the Macular Society (22-RG-1), a PhD studentship from Moorfields Eye Charity (GR001499) and further supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Authors’ contributions MDC led on design of the work, acquisition, analysis and interpretation of data and drafted the manuscript. MST contributed to design of the work, interpretation of data and revision of manuscript. LW contributed to acquisition of data. RFC contributed to acquisition of data. TMD contributed to design of the work. MM contributed to design of the work and acquisition of data. All authors read and approved the final manuscript. Acknowledgements We would like to thank Bhavna Tailor, Stargardt’s Connected and the Moorfields Eye-Young Person’s Advisory Group for their advice and support with this study; and Tomás Hart-Shea for providing participant feedback. References Bonsaksen T, Brunes A, Heir T. Quality of life in people with visual impairment compared with the general population. J Public Health [Internet]. 2023 [cited 2024 Dec 12]; https://doi.org/10.1007/s10389-023-01995-1 Crossland MD, Dekker TM, Tibber MS. Association between self-reported vision and mental well-being: a cross-sectional secondary analysis of Health Survey for England data. BMJ Open. British Medical Journal Publishing Group; 2025;15:e101753. https://doi.org/10.1136/bmjopen-2025-101753 Xiang X, Freedman VA, Shah K, Hu RX, Stagg BC, Ehrlich JR. 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Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 14 Feb, 2026 Reviews received at journal 13 Feb, 2026 Reviewers agreed at journal 23 Jan, 2026 Reviews received at journal 15 Dec, 2025 Reviewers agreed at journal 27 Oct, 2025 Reviewers invited by journal 23 Oct, 2025 Editor assigned by journal 23 Oct, 2025 Submission checks completed at journal 22 Oct, 2025 First submitted to journal 21 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Crossland","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYBADGSA2fMDAYAHmMTYQoYUHiI0NGBgkSNNiJkGUFt0G5mcfPvyp4+Gf3bytmqdGgoG//QCb5Aw8WswOsBnPnNl2mEfizrGy2zzHJBgkziSwSW7Aq4WHmZm34QAPw40cs9u8DUCH3WBgk3xASAsP0GHyQC3FIC3yxGlhY+YxAGphBmkxAGnB67DDbMaMIL8Y3kgrlpxzTILH8ExisyVe7x9vfswADDE5uRvJGz+8qbGRkzt++ODNHjxaGJjR+DxERuQoGAWjYBSMAnwAAPJSQsWYIfLJAAAAAElFTkSuQmCC","orcid":"","institution":"UCL Institute of Ophthalmology","correspondingAuthor":true,"prefix":"","firstName":"Michael","middleName":"D.","lastName":"Crossland","suffix":""},{"id":534098849,"identity":"e78f08e0-9c4f-4b6c-9bee-508161f4504f","order_by":1,"name":"Marc S. 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Dekker","email":"","orcid":"","institution":"UCL Institute of Ophthalmology","correspondingAuthor":false,"prefix":"","firstName":"Tessa","middleName":"M.","lastName":"Dekker","suffix":""},{"id":534098856,"identity":"11a42e55-56f7-45f5-9414-339137e220a2","order_by":5,"name":"Michel Michaelides","email":"","orcid":"","institution":"UCL Institute of Ophthalmology","correspondingAuthor":false,"prefix":"","firstName":"Michel","middleName":"","lastName":"Michaelides","suffix":""}],"badges":[],"createdAt":"2025-10-22 08:10:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7917603/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7917603/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":94250937,"identity":"3edce8e7-5281-4399-9c03-50acc0df5dc4","added_by":"auto","created_at":"2025-10-24 06:52:30","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":78903,"visible":true,"origin":"","legend":"","description":"","filename":"LonelinessWellbeingManuscriptOPOFINAL.docx","url":"https://assets-eu.researchsquare.com/files/rs-7917603/v1/a3f76eb44f4504800cfbbb74.docx"},{"id":94250704,"identity":"83da3ef9-8e83-47cd-8ed5-88089a7ce223","added_by":"auto","created_at":"2025-10-24 06:44:30","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8603,"visible":true,"origin":"","legend":"","description":"","filename":"35273b4fdaa14e7290136b28fb51be01.json","url":"https://assets-eu.researchsquare.com/files/rs-7917603/v1/0b04ed9eda0f09ffa05f65bf.json"},{"id":94250707,"identity":"b2ef4af3-8592-45e9-b3ea-f11caa828b68","added_by":"auto","created_at":"2025-10-24 06:44:30","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":91671,"visible":true,"origin":"","legend":"","description":"","filename":"35273b4fdaa14e7290136b28fb51be011enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7917603/v1/5ddeabaf18cd96a13c98a516.xml"},{"id":94250708,"identity":"560fefcb-7d30-41a7-aa0b-732951d9249d","added_by":"auto","created_at":"2025-10-24 06:44:30","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":88596,"visible":true,"origin":"","legend":"","description":"","filename":"35273b4fdaa14e7290136b28fb51be011structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7917603/v1/6b55f9d570b3ef217a7a33b1.xml"},{"id":94250706,"identity":"25b3f46a-8ec0-4079-951f-7732eb05314b","added_by":"auto","created_at":"2025-10-24 06:44:30","extension":"html","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":101022,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7917603/v1/4fe1f0b737640e88657b30ee.html"},{"id":94251893,"identity":"d2f46ac1-a782-4103-9e80-519feb5bbb87","added_by":"auto","created_at":"2025-10-24 07:00:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":948895,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7917603/v1/0c55c2aa-d306-4215-b550-ebf97bba42e2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Loneliness and mental wellbeing in people with inherited macular disease","fulltext":[{"header":"Key Points","content":"\u003col\u003e\n \u003cli\u003eMental wellbeing for our participants with inherited macular disease, who had access to low vision clinics and other support services, was similar to the general population;\u003c/li\u003e\n \u003cli\u003eParticipants reporting higher levels of loneliness had lower levels of mental wellbeing than those who were less lonely;\u003c/li\u003e\n \u003cli\u003eThis relationship persisted after controlling for mental ill-health, demographic or disease factors which could affect wellbeing.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eMental wellbeing is reduced in people with vision impairment,[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] but the reasons for this are not fully understood. Previous research has identified a variety of factors associated with poorer wellbeing in this population, including loneliness, lower social support, lower self-efficacy, unemployment and having a later onset of vision impairment.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eLoneliness is strongly associated with reduced wellbeing, depression, anxiety, mental ill-health, poor physical health and increased mortality in the general population.[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] On average, people with vision impairment report higher levels of loneliness [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and this is associated with lower life satisfaction [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and depression.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Loneliness appears to be more likely in adults with vision impairment who live alone, who have limited mobility, who are not working or studying and who do not describe themselves as religious.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] This suggests loneliness is not a direct consequence of eye disease, but rather an indirect effect of the isolation and activity limitation which can be associated with vision impairment.\u003c/p\u003e\u003cp\u003eAs well as having lower wellbeing, people with vision impairment are far more likely to experience depression [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and anxiety [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] than their peers without sight loss. Although mental wellbeing is a broader concept than just the absence of mental ill-health, wellbeing is generally lower in people with depression or anxiety, which may confound previous research showing a relationship between loneliness and wellbeing in people with vision impairment.\u003c/p\u003e\u003cp\u003eTo date, most research on wellbeing in people with eye disease has investigated older adults, with studies typically combining different causes of vision impairment, including (in some cases) cerebral vision impairment and syndromic conditions. However, different diseases may impact wellbeing in different ways. For example, the psychological impact of lifelong cerebral visual impairment is likely to be very different to having peripheral vision loss from glaucoma in later life, or central vision loss from inherited macular disease as a teenager. The wellbeing of adolescents with vision impairment is largely unexplored.\u003c/p\u003e\u003cp\u003eIn this paper we explore the relationship between loneliness and mental wellbeing in a group of adolescents and adults with a single, non-syndromic, ocular cause of vision impairment: inherited macular disease. We control for demographic and socioeconomic (age, sex, ethnic origin, socioeconomic status), clinical (visual acuity, duration of disease) and mental health (depression and anxiety) variables, all of which are known to affect wellbeing. We hypothesised that mental wellbeing would be lower in people with vision impairment who have higher levels of loneliness, even after controlling for these covariates.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003eThis was a cross-sectional observational study evaluating the wellbeing of people with vision impairment caused by inherited macular disease.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003ePatient and public involvement and engagement\u003c/h3\u003e\n\u003cp\u003eThe study was developed in collaboration with people with lived experience of vision impairment and their families, including representatives from the Stargardt\u0026rsquo;s Connected charity and the Moorfields Eye-Young Persons\u0026rsquo; Advisory Group, who also reviewed the participant information documents.\u003c/p\u003e\u003cp\u003eOne of the participants was asked to provide feedback on an early draft of this manuscript and evaluate the study with particular reference to the accessibility and ease of engagement in the study; their satisfaction with their participation in the study; and their comments on the clarity of the manuscript.\u003c/p\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003ePeople aged 13 years or older attending genetic eye disease or low vision clinics at Moorfields Eye Hospital who had a diagnosis of inherited macular disease were invited to participate. As assessed by the study team, those who did not have sufficient English language skills to complete the assessments, or who had hearing loss that affected their ability to complete telephone assessments, were excluded.\u003c/p\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eDemographic details including age, sex and ethnicity were extracted from hospital records, as were relevant medical details (type of inherited macular disease, time of diagnosis, time of symptom onset, visual acuity in the better eye). Age was categorised as adolescent (13\u0026ndash;18 years), emerging adult (18\u0026ndash;29 years), adult (30\u0026ndash;64 years) and older adult (\u0026gt;\u0026thinsp;64 years). Visual acuity was categorised as mild, moderate, severe or blind, in line with ICD-11 guidelines [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Participants\u0026rsquo; home postcode using the 2019 English indices of deprivation, which links socioeconomic status to residents\u0026rsquo; lower-layer super output area (a region of approximately 400\u0026ndash;1200 households, or 1000\u0026ndash;3000 people) was used as a proxy for socioeconomic status.[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e\u003cp\u003e Loneliness, depression, anxiety and mental wellbeing were measured during a single telephone call between each participant and a member of the study team, at a time of the participant\u0026rsquo;s choosing.\u003c/p\u003e\u003cp\u003eLoneliness was measured using the UCLA loneliness scale version 3 [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] for adolescents (aged 13\u0026ndash;17 years), and the revised UCLA loneliness scale [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] for those over 18 years. These instruments comprise 20 items, have 4 response levels, and have high internal consistency, construct validity and test-retest correlation. Higher values on these scales relate to greater loneliness.\u003c/p\u003e\u003cp\u003eDepression was measured using the 25-item (4-response level) Revised Children\u0026rsquo;s Anxiety and Depression Scale (RCADS-25 [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]) in adolescents, and the 9-item, 4-response level, Patient Health Questionnaire 9 (PHQ-9 [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]) in adults. Anxiety was measured using the RCADS-25 in adolescents and the Generalized Anxiety Disorder-7 (GAD-7 [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]) 7-item, 4-response level instrument in adults.\u003c/p\u003e\u003cp\u003eMental wellbeing was measured with the Warwick Edinburgh Mental Wellbeing Scale (WEMWS) for all participants. [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] On this scale, higher values correspond to more anxiety, depression, and better wellbeing, respectively. All have been well validated and show robust psychometric properties.[\u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eAt the end of the data collection session, participants were offered referral to age-appropriate counselling services. A suicide and self-harm risk assessment protocol was in place, developed by a senior clinical psychologist (author MST). All members of the research team were offered clinical supervision and had access to confidential counselling services.\u003c/p\u003e\n\u003ch3\u003eStatistical design\u003c/h3\u003e\n\u003cp\u003eData were collected using the secure Research Electronic Data Capture (REDCap) system hosted by University College London and stored in a secure database. All data were tested for normality using the Shapiro Wilk test, with log transformations being performed where data departed from normality at the \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 level.\u003c/p\u003e\u003cp\u003eAnalysis of variance (ANOVA) was used to compare wellbeing values to benchmark data from the Health Survey for England.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] Descriptive statistics were used to identify caseness for depression and anxiety for included participants. Caseness is a term widely used in psychiatry, which refers to meeting the diagnostic threshold for a disorder. RCADS-25 data were converted to T-scores, normalised by age and gender, for depression and anxiety, based on Ebesutani\u0026rsquo;s dataset.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] T-scores\u0026thinsp;\u0026lt;\u0026thinsp;65 were defined as in the \u0026lsquo;normal range,\u0026rsquo; between 65 and 69 as in the \u0026lsquo;borderline clinical range,\u0026rsquo; and of 70 and above as in the \u0026lsquo;clinical range.\u0026rsquo; For adults, following clinical recommendations, caseness for depression and anxiety were defined as scores of \u0026ge;\u0026thinsp;10 on the PHQ-9[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and GAD-7[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], respectively. This allowed for comparison between adolescents and adults.\u003c/p\u003e\u003cp\u003eTo explore the relationship between wellbeing and loneliness, several linear regression analyses were performed. First, a series of univariate regression analyses were undertaken, regressing wellbeing (separately) on loneliness and covariates including demographic (age, gender, ethnic origin, socioeconomic status), clinical (visual acuity, duration of disease), and mental health (caseness for depression and anxiety) variables to explore basic patterns of association. Next, two additional models were run, using forward stepwise multivariate regression. In the first, wellbeing was regressed on loneliness, with demographic and clinical variables assessed for inclusion; in the second, the same model was run, with mental health variables also assessed for inclusion.\u003c/p\u003e\u003cp\u003eAnalyses were performed in JMP Pro (v. 18.2.2, JMP Statistical Discovery LLC, Cary, North Carolina, USA).\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThirty-six participants were recruited. Participants\u0026rsquo; demographic, socioeconomic, clinical and mental health characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Duration of disease and loneliness data were positively skewed and were log transformed.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eParticipant demographics and clinical characteristics.\u003c/b\u003e IMD: inherited macular disease.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNumber (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u003cb\u003eAge group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAdolescent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEmerging adult\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (17%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAdult\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (44%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOlder adult\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (24%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (47%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (53%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u003cb\u003eEthnic group\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAsian or Asian British\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (36%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMixed or multiple ethnic groups\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (17%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eWhite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (36%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNot stated\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (11%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"10\" rowspan=\"11\"\u003e\u003cp\u003e\u003cb\u003eSocioeconomic status (decile)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (most deprived)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (21%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (12%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (12%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (12%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (12%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (least deprived)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMissing data\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003e\u003cb\u003eDisease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eABCA4/Stargardt\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (56%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBest disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOther IMD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGenetically Unconfirmed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (11%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e\u003cp\u003e\u003cb\u003eVision impairment category\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNot vision impaired\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (5.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMild\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (19%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (47%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSevere\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (19%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBlind\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (14%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eAnxiety Caseness\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (25%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (75%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003eDepression Caseness\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (17%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30 (83%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eMedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDuration of disease\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYears\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (25)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLoneliness\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUCLA scale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31 (15)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe mean wellbeing score, measured on the WEMWS, was 50.9 (sd: 9.7). On average, participants\u0026rsquo; wellbeing was not significantly different to that of the general population (general population; mean\u0026thinsp;=\u0026thinsp;51.4; sd: 9.42; this study: mean: 50.9, sd: 9.68; ANOVA, \u003cem\u003eF\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.099, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.75). Ten of our participants had \u0026lsquo;moderate\u0026rsquo; levels of loneliness and five had \u0026lsquo;moderate/high\u0026rsquo; loneliness.\u003c/p\u003e\u003cp\u003eUnivariate linear regression showed a significant linear association between wellbeing and loneliness (\u003cem\u003er\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.35, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). With respect to other variables explored, wellbeing was significantly associated with depression (\u003cem\u003er\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.27, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and anxiety (\u003cem\u003er\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.24, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01) \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e. None of the demographic or clinical variables, including severity of vision loss, were related to wellbeing (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Loneliness was not correlated with having depression (\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.0023, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.96) or anxiety (\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;1.13, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.29).\u003c/p\u003e\u003cp\u003eIn the first stepwise regression (in which demographic, socioeconomic and clinical variables were added), the association between wellbeing and loneliness remained significant (\u003cem\u003er\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.31, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and gender was retained (\u003cem\u003er\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.43, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05); overall, the model accounted 47% of the variance in wellbeing (\u003cem\u003er\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.474). In the second stepwise regression model (in which anxiety and depression were also added), the association between wellbeing remained significant (\u003cem\u003er\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.27, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and gender, depression and anxiety were retained; overall, the model accounted for 61% of the variance in wellbeing (\u003cem\u003er\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.613).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eResults of univariate and multivariate regression analyses of wellbeing.\u003c/b\u003e UCLA: University of California Los Angeles loneliness scale. CI: confidence interval.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eUnivariate models\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMultivariate model with demographic and clinical variables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMultivariate model with demographic, clinical and mental ill-health variables\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCoefficient\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCoefficient\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCoefficient\u003c/p\u003e\u003cp\u003e(95% CI)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLoneliness\u003c/p\u003e\u003cp\u003e(log UCLA score)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e-38.7\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(-57, -20)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-37.2\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(-54, -20)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e-35.7\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(-51, -20)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e\u0026lt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge group\u003c/p\u003e\u003cp\u003e(adolescent)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.30\u003c/p\u003e\u003cp\u003e(-0.88, 5.48)\u003c/p\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003cp\u003e(female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.85\u003c/p\u003e\u003cp\u003e(-0.21, 5.9)\u003c/p\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e-3.18\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(-5.5, -0.83)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1.83\u003c/p\u003e\u003cp\u003e(-4.1, 0.47)\u003c/p\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEthnic group (white British)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-2.07\u003c/p\u003e\u003cp\u003e(-5.54, 1.40)\u003c/p\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSocioeconomic status\u003c/p\u003e\u003cp\u003e(least deprived)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.25\u003c/p\u003e \u003cp\u003e(-1.45, 0.95)\u003c/p\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVision impairment level\u003c/p\u003e\u003cp\u003e(none)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.15\u003c/p\u003e\u003cp\u003e(-3.37, 3.08)\u003c/p\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration of disease\u003c/p\u003e\u003cp\u003e(log years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-2.39\u003c/p\u003e\u003cp\u003e(-9.2, 4.5)\u003c/p\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDepression\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e-6.67\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(-10, -2.9)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e-3.76\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(-7.3, -0.26)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e\u0026lt;\u0026thinsp;0.05\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnxiety\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e-5.37\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(-8.7, 2.0)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003ep\u003c/b\u003e\u0026thinsp;\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-2.05\u003c/p\u003e\u003cp\u003e(-4.8, 0.67)\u003c/p\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.14\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eParticipant review\u003c/h3\u003e\n\u003cp\u003eThe participant confirmed that the study asked an important research question, used appropriate methods and recruited an appropriate population. He did not experience any accessibility problems with the study and did not find any of the questions asked ambiguous. He made some comments on the readability of the manuscript (specifically, the use of acronyms), which have been incorporated.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eAs hypothesised, we found an association between loneliness and mental wellbeing in adolescents and adults with inherited eye disease, with people who reporting higher levels of loneliness also reporting lower levels of wellbeing. This supports the findings of other research linking loneliness to wellbeing in eye disease [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] and extends these findings by showing that this relationship remained significant after controlling for demographic, socioeconomic, clinical and mental health variables. Depression and anxiety were also associated with lower levels of wellbeing, but demographic and clinical factors were not.\u003c/p\u003e\u003cp\u003eLevels of wellbeing experienced by our participants were broadly similar to the general population. The discrepancy between this finding and previous work, which showed lower levels of wellbeing in people with vision impairment relative to the general population, [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] might be due to our participants being recruited from a specialist ophthalmology centre, where they had access to low vision assessment, counselling, emotional and genetic counselling, eye clinic liaison officers and expert ophthalmology care. Thus, participation biases may have excluded those with the lowest levels of wellbeing.\u003c/p\u003e\u003cp\u003eLow mental wellbeing is known to be a risk factor for the development of major depression.[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Encouragingly, the most significant predictor of reduced wellbeing which we identified \u0026ndash; loneliness - appears to be potentially modifiable, for example, by social prescribing [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and mentoring programmes.[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] A particularly encouraging finding of our work is that there was no association between wellbeing and \u003cem\u003enonmodifiable\u003c/em\u003e risk factors, such as age, ethnicity, disease severity and disease duration. The severity of vision loss can not be taken as a simple index of wellbeing or mental ill-health risk; instead the relationship between eye disease and wellbeing is likely to be more complex and dependent on multiple social and environmental factors.\u003c/p\u003e\u003cp\u003eUnlike Verstraten and colleagues,[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] who measured loneliness and depression in a cohort of older adults, we did not find a relationship between depression and loneliness. The reason for this apparent discrepancy is unclear, though the lower and broader age distribution of our sample is one possibility. For example, the effects of loneliness may be elevated in older populations, who commonly experience greater levels of social isolation.[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eWould depression and loneliness affect wellbeing to the same extent in people \u003cem\u003ewithout\u003c/em\u003e vision impairment? Perhaps, but as depression [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and loneliness [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] are both higher in people with vision impairment, we believe that the impact of these factors on wellbeing in this population is particularly important. Interventions to target loneliness (such as social prescribing, support groups and befriending services) and depression (such as counselling and prompt referral to mental health services) should be tailored and offered to people with vision impairment and evaluated empirically.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eOne limitation of our study is its relatively small sample size, largely caused by the relative rarity of inherited macular disease. A further limitation was that our study was cross-sectional in nature, so we were are unable to infer causation, or the underlying direction thereof. However, we are in the process of collecting longitudinal data from the adolescent participants in this study.\u003c/p\u003e\u003cp\u003eAs discussed above, our participants may not be fully representative of the general population with inherited macular disease. People with vision impairment who are medically excluded, or those who do not have access to a specialist centre with such a comprehensive support service, may have lower wellbeing when compared to people included in this study. All of our participants had \u0026lsquo;low,\u0026rsquo; \u0026lsquo;moderate\u0026rsquo; or \u0026lsquo;moderate/high\u0026rsquo; levels of loneliness, with none having the highest level of loneliness as measured on the UCLA scale. Additionally, all of our participants received services through the National Health Service, free of charge at the point of delivery, which may limit the applicability of our results to non-European settings.\u003c/p\u003e\u003cp\u003eAlthough we did not find an impact of socioeconomic status on mental health, people from areas of higher social deprivation are less likely to access eyecare [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and may be less likely to have been recruited for the present study. Further, our method of using an area level proxy for socioeconomic status is a relatively unreliable method.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eWe found loneliness to be strongly associated with reduced wellbeing in a group of adolescents and adults with vision impairment caused by inherited macular disease. Disease factors such as the severity of vision loss can not be used as a proxy or a predictor of likely wellbeing. The role of interventions which support loneliness, such as social prescribing and mentoring, should be explored for people with vision impairment.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eANOVA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eanalyses of variance\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGAD-7\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGeneralized Anxiety Disorder-7 instrument\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIMD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003einherited macular disease\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePHQ-9\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePatient Health Questionnaire-9\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eRCADS-25\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003e25-item Revised Children\u0026rsquo;s Anxiety and Depression Scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eREDCap\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eResearch Electronic Data Capture\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eWEMWS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eWarwick Edinburgh Mental Wellbeing Scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was performed in accordance with the Declaration of Helsinki and received ethical approval from the Health Research Authority (IRAS number 326182) following review by the London - City \u0026amp; East Research Ethics Committee. All adult participants gave informed consent before data collection. Participants under the age of 18 assented to taking part in the study and informed consent was obtained from a parent or carer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest disclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was funded by a project grant from the Macular Society (22-RG-1), a PhD studentship from Moorfields Eye Charity (GR001499) and further supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMDC led on design of the work, acquisition, analysis and interpretation of data and drafted the manuscript. MST contributed to design of the work, interpretation of data and revision of manuscript. LW contributed to acquisition of data. RFC contributed to acquisition of data. TMD contributed to design of the work. MM contributed to design of the work and acquisition of data. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Bhavna Tailor, Stargardt\u0026rsquo;s Connected and the Moorfields Eye-Young Person\u0026rsquo;s Advisory Group for their advice and support with this study; and Tom\u0026aacute;s Hart-Shea for providing participant feedback.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBonsaksen T, Brunes A, Heir T. Quality of life in people with visual impairment compared with the general population. J Public Health [Internet]. 2023 [cited 2024 Dec 12]; \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s10389-023-01995-1\u003c/span\u003e\u003cspan address=\"10.1007/s10389-023-01995-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCrossland MD, Dekker TM, Tibber MS. Association between self-reported vision and mental well-being: a cross-sectional secondary analysis of Health Survey for England data. BMJ Open. 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Deprivation and NHS General Ophthalmic Service sight testing activity in England in 2022\u0026ndash;2023. Ophthalmic Physiol Opt. 2025;45:294\u0026ndash;300. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/opo.13399\u003c/span\u003e\u003cspan address=\"10.1111/opo.13399\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"ophthalmic-and-physiological-optics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Ophthalmic and Physiological Optics](https://link.springer.com/journal/44402)","snPcode":"44402","submissionUrl":"https://submission.springernature.com/new-submission/44402/3?","title":"Ophthalmic and Physiological Optics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"loneliness, low vision, macula, inherited, vision impairment, wellbeing","lastPublishedDoi":"10.21203/rs.3.rs-7917603/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7917603/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003ePeople with vision impairment have lower mental wellbeing than people without eye disease. Loneliness is thought to be associated with lower wellbeing in this population, but the confounding effect of mental ill-health and other factors which affect wellbeing has not been addressed. Here, we explored associations between loneliness and wellbeing in people with inherited macular disease, controlling for mental ill-health, demographic and clinical factors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eThirty-six people with inherited macular disease were recruited. Age, visual acuity, duration of disease and socioeconomic status were extracted from hospital notes. Loneliness, depression, anxiety and mental wellbeing were assessed using self-report questionnaires. Wellbeing was compared to a reference population of adults in the United Kingdom. Univariate and stepwise multivariate regression was used to examine the association between loneliness and wellbeing, controlling for demographic, clinical and mental health factors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eOn average, participants’ wellbeing was not significantly different to the reference population (this study: mean: 50.9, sd: 9.68; reference population; mean=51.4; sd: 9.42; ANOVA, \u003cem\u003eF\u003c/em\u003e = 0.099, \u003cem\u003ep\u003c/em\u003e = 0.75). Univariate linear regression showed significant associations between wellbeing and loneliness (\u003cem\u003eb\u003c/em\u003e = -38.7; 95%CI -57, -20; \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.0001), depression (\u003cem\u003eb\u003c/em\u003e = -6.67; 95%CI -10, -2.9; \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.0001) and anxiety (\u003cem\u003eb\u003c/em\u003e = -5.37; 95%CI -8.7, 2.0; \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.0001). None of the other demographic and clinical variables were related to wellbeing at the \u003cem\u003ep\u003c/em\u003e = 0.05 level. Stepwise regression revealed loneliness, gender, depression and anxiety to be (together) significantly associated with wellbeing, accounting for 61% of the variance in wellbeing (\u003cem\u003er\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e = 0.613).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eLoneliness was associated with lower mental wellbeing even after controlling for mental ill-health, demographic and clinical factors. The severity of vision loss can not be taken as a simple index of likely wellbeing. Interventions which target loneliness may help maximise wellbeing in people with inherited macular disease.\u003c/p\u003e","manuscriptTitle":"Loneliness and mental wellbeing in people with inherited macular disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-24 06:44:25","doi":"10.21203/rs.3.rs-7917603/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-14T10:55:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-13T15:19:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"161670969794969498173499538934457127808","date":"2026-01-23T12:43:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-15T15:27:41+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"137024758023642305377296935647995326735","date":"2025-10-27T10:04:35+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-23T16:46:02+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-23T16:44:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-23T01:44:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Ophthalmic and Physiological Optics","date":"2025-10-21T16:11:14+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"ophthalmic-and-physiological-optics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Ophthalmic and Physiological Optics](https://link.springer.com/journal/44402)","snPcode":"44402","submissionUrl":"https://submission.springernature.com/new-submission/44402/3?","title":"Ophthalmic and Physiological Optics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b820dd12-e250-47c7-ba55-ce929cf67979","owner":[],"postedDate":"October 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-30T18:09:25+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-24 06:44:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7917603","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7917603","identity":"rs-7917603","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}