Lawrence Claire, Williams Emma, Mumford Andrew, Bojakowski Steve, Benedicto Julio, Lloyd Andrew
Acaster Lloyd, Lacon House, 84 Theobalds Rd, London, WC1X 8NL, UK.
Trustee, LHON Society, The Hayloft, Pury Hill Business Park, Alderton, Northamptonshire, NN12 7LS, UK.
Orphanet J Rare Dis. 2025 May 7;20(1):219. doi: 10.1186/s13023-025-03737-w.
Leber hereditary optic neuropathy (LHON) is a rare, maternally inherited, mitochondrial disease resulting in sudden, progressive central vision loss. The condition affects numerous aspects of daily life, functioning and overall health-related quality of life (HRQL), which may spillover to carers.
Two studies were designed to estimate patient utilities associated with varying visual acuity in LHON (study 1) and to explore carer burden (study 2). In study 1, eight LHON health state vignettes (mild vision loss [LogMAR < 0.3] through to light perception [LogMAR ≥ 4]) were valued by the UK and Republic of Ireland (ROI) general pubic using the Health Utilities Index- 3 (HUI-3) and EQ-5D in an online survey (N = 360) and in time trade-off interviews (TTO; n = 120). In study 2, nine carers completed in-depth interviews exploring carer burden, the Care-related Quality of Life instrument (CarerQol), EQ-5D-5L and the Work Productivity and Activity Impairment Questionnaire (WPAI).
Study 1 demonstrated lower utilities for people with worse visual function. Mild vision loss (LogMAR < 0.3) was rated as 0.84 (HUI-3), 0.79 (EQ-5D) and 0.88 (TTO). Light perception (LogMAR ≥ 4), the most severe health state, was rated as 0.18 (HUI-3), 0.34 (EQ-5D), and 0.36 (TTO). In study 2, qualitative findings revealed substantial burden for many carers and family members. The most prominent impacts were emotional (e.g., guilt, devastation), especially related to the maternal inheritance of LHON. Impacts to carers' daily life, social life and relationships, work, and finances were also described. Standardised measures identified little impact on HRQL (EQ-5D-5L = 0.89), but some carer related burden (CarerQol-7D = 78.4). The WPAI revealed an overall work impairment of 15% and activity impairment of 37%.
Findings suggest the HUI-3 may be more sensitive to the HRQL impact of vision loss compared to the EQ-5D and TTO method. The data indicate the potential value of an effective treatment for LHON. Qualitative findings describe the impact of LHON on carers. However, the burden described in the qualitative data was incongruent with quantitative measures, particularly the EQ-5D-5L. This demonstrates the value of conducting mixed-methods research and the importance of selecting measures which capture population-relevant concepts.
Leber遗传性视神经病变（LHON）是一种罕见的母系遗传线粒体疾病，可导致突然的、进行性的中心视力丧失。该疾病会影响日常生活、功能以及整体健康相关生活质量（HRQL）的诸多方面，且这种影响可能会波及到照料者。
设计了两项研究，一项旨在评估LHON患者不同视力水平下的健康效用值（研究1），另一项旨在探究照料者负担（研究2）。在研究1中，通过在线调查（N = 360）以及时间权衡访谈（TTO；n = 120），让英国和爱尔兰共和国（ROI）的普通公众使用健康效用指数-3（HUI-3）和EQ-5D对八个LHON健康状态 vignettes（从轻度视力丧失[LogMAR＜0.3]到光感[LogMAR≥4]）进行估值。在研究2中，九名照料者完成了深入访谈，探讨照料者负担、与照料相关的生活质量量表（CarerQol）、EQ-5D-5L以及工作生产力和活动障碍问卷（WPAI）。
研究1表明，视力功能越差的人健康效用值越低。轻度视力丧失（LogMAR＜0.3）在HUI-3中的评分为0.84，在EQ-5D中的评分为0.79，在TTO中的评分为0.88。光感（LogMAR≥4）这一最严重的健康状态，在HUI-3中的评分为0.18，在EQ-5D中的评分为0.34，在TTO中的评分为0.36。在研究2中，定性研究结果显示许多照料者和家庭成员负担沉重。最突出的影响是情感方面的（如内疚、悲痛），尤其与LHON的母系遗传有关。还描述了对照料者日常生活、社交生活及人际关系、工作和财务的影响。标准化测量显示对HRQL影响较小（EQ-5D-5L = 0.89），但存在一些与照料者相关的负担（CarerQol-7D = 78.4）。WPAI显示总体工作障碍为15%，活动障碍为37%。
研究结果表明，与EQ-5D和TTO方法相比，HUI-3可能对视功能丧失的HRQL影响更敏感。数据表明有效治疗LHON的潜在价值。定性研究结果描述了LHON对照料者的影响。然而，定性数据中描述的负担与定量测量结果不一致，尤其是EQ-5D-5L。这证明了开展混合方法研究的价值以及选择能够捕捉与人群相关概念的测量方法的重要性。
