Secondary Logo

Journal Logo

Original Contribution

Evaluation of Vision-Related Quality of Life in Chinese Patients With Leber Hereditary Optic Neuropathy and the G11778A Mutation

Cui, Shilei MD; Jiang, Hanqiu MD, PhD; Peng, Jingting MD, PhD; Wang, Jiawei MD, PhD; Zhang, Xiaojun MD, PhD

Author Information
Journal of Neuro-Ophthalmology: March 2019 - Volume 39 - Issue 1 - p 56-59
doi: 10.1097/WNO.0000000000000644

Abstract

Health-related quality of life (HR-QoL) describes the social, emotional, and physical impact of illness from the patient's perspective, and it is increasingly used by health care professionals as a comprehensive assessment tool, especially in the setting of chronic diseases. The marked reduction in visual acuity in patients with LHON leads to a profound impact on quality of life (QoL) and independence. However, the data of quality of life in LHON are very limited. Kirkman et al (1) reported that LHON has a severe negative impact on HR-QoL, especially in activities involving reading small print. However, this was a multicenter, cross-sectional study and evaluated quality of life measures at a single point in time.

We present the results of a prospective, longitudinal study on HR-QoL in Chinese LHON patients with the G11778A mutation evaluated at one medical institution. Scores for each item of the VF-14 were compared over time to explore whether patients reported any changes in the quality measures.

METHODS

Patients

This study was approved by the Institute Review Board of Beijing Tongren Hospital, Capital Medical University, China. All LHON patients with the G11778A mutation were identified from the LHON clinical database. Patients were recruited from October 1, 2009, to December 31, 2013, and assessed by an experienced neuro-ophthalmologist. Clinical diagnoses were made based on sequentially bilateral painless visual loss, typical optic disc findings, and central visual field loss. Diagnosis of G11778A mtDNA mutation was established by polymerase chain reaction and direct sequencing. Patients were followed up every 6 months through telephone or at an outpatient clinic. Follow-up times range from 3 to 4 years. Verbal informed consent was obtained from each patient, and all procedures were in compliance with the tenets of the Declaration of Helsinki. The participants received no financial compensation.

LHON patients with the G11778A mutation who met the following criteria were included in this study: (A) Have completed the VF-14 index survey at 6 months, 1 year, and 3 years after involvement of the second eye. (B) No concomitant disease that could lead to disability.

VF-14 Index

An experienced investigator interviewed each patient and administered the VF-14 index questionnaire, which measures the ability of individuals to perform 12 vision-dependent activities of daily living. These activities were rated according to difficulty, with 5 possible scores for each question: 0 (unable to do), 1 (great deal of difficulty), 2 (moderate difficulty), 3 (little difficulty), and 4 (no difficulty). The patients were asked to give answers that incorporated the use of reading glasses but not magnification aids. A question was not included whether an activity was not performed by an individual for reasons unrelated to disease status. An average score was then generated from all the answered questions and multiplied by 25 to yield an overall visual function score ranging from 0 (worst level) to 100 (best level). The VF-14 has been adapted and validated in China (2,3), and we used this version in our study.

Statistical Analysis

Statistical analyses were performed using Statistical Package for Social Sciences 18.0.0 (IBM Corporation, Armonk, NY). P values of <0.05 were taken to indicate statistical significance.

Descriptive Analysis and Item Analysis

The normality of each variable was checked using the One-sample Kolmogorov–Smirnov test. Snellen visual acuity was converted to logMAR for statistical analysis. All VF-14 scores at each follow-up time point were normal distribution, whereas age, visual acuity, and change of VF-14 score between 6-month and 3-year follow-ups were non-normal distribution. All continuous variables with normal distribution were expressed as the mean ± SDs except age and best-corrected visual acuity. For the latter, we used median and interquartile range. Paired sample t test was used to compare VF-14 scores between different follow-up time points if data had a normal distribution. Item analysis was performed using data from our study and that of Kirkman et al (1). Comparisons were made using Pearson chi-square test or Wilcoxon rank sum test when chi-square test was not appropriate.

Logistic Regression Test

We defined the onset age of the second eye (categorized as <14 years or ≥14 years) and Snellen visual acuity (categorized as <0.1 or ≥0.1) of the better eye as dependent variables. A VF-14 score of <20 at the 6-month follow-up was defined as seriously impaired visual-related quality of life, and ≥20 was defined as relatively better. An increase of ≥4 of the VF-14 score from the 6-month to 3-year follow-up was defined as improvement of QoL. Logistic regression test was used to investigate whether these variables were correlated with VF-14 scores at the early stage and the improvement of QoL.

RESULTS

Seventy-three Chinese LHON patients with the G11778A mutation were identified from our database. Fifty-five patients met our inclusion criteria and were followed for at least 3 years. This cohort had a median age of onset of bilateral visual loss of 16.3 years (interquartile range: 13.9–18.3 years), 89.1% (n = 49) were male, and the ratio of males to females was 8.2:1. The median logMAR visual acuity was 2.0 (interquartile range: 1.0–2.6). Further patient characteristics are shown in Table 1.

TABLE 1.
TABLE 1.:
Clinical characteristics of Chinese patients with LHON

VF-14 scores at 6-month, 1-year, and 3-year follow-ups are also shown in Table 1. The mean VF-14 score of LHON patients with the G11778A mutation at 1-year follow-up (mean 19.9, SD: 20.0) was significantly higher than that at the 6-month follow-up (mean 18.0, SD: 19.2, P < 0.001). The mean VF-14 score at 3-year follow-up (mean 20.7, SD: 20.2) also was significantly higher than that at 1-year follow-up (P < 0.001). The median increase of VF-14 from 6-month to 3-year follow-up was 2.1 (interquartile range: 0–2.5).

Logistic regression analysis test showed that the VF-14 score at 6 months was significantly correlated with visual acuity (P < 0.001), but not correlated with age of onset (P = 0.43). There was no significant correlation between the visual acuity of the better eye and the age of onset (P = 0.268). The QoL improvement was significantly correlated with age of onset (P = 0.006), but not correlated with visual acuity of the better eye (P = 0.134) (See Supplement Digital Content, Table E1, http://links.lww.com/WNO/A304).

Several measures of QoL were significantly improved at the 1-year follow-up compared with the 6-month follow-up, including seeing steps, curbs, or stairs (P < 0.01), doing handiwork (P < 0.05), playing sports (P < 0.05), cooking (P < 0.01), and watching television (P < 0.05) (See Supplement Digital Content, Table E2, http://links.lww.com/WNO/A305). Only scores for cooking (P < 0.05) and watching television (P < 0.05) were significantly higher at the 3-year follow-up than at the 1-year follow-up. No changes in reading small print, reading a newspaper or a book, or reading signs were found during the follow-up.

We compared our findings to these reported by Kirkman et al (1) (See Supplement Digital Content, Table E2, http://links.lww.com/WNO/A305). No statistically significant differences were found between the 2 groups for any of the other items.

DISCUSSION

Most patients in our LHON cohort experienced vision loss in their teens, and the male-to-female ratio in our group was slightly higher than that reported in previous case series (4–6). Although male carriers are more likely to be affected than female carriers, this higher male-to-female ratio discrepancy might reflect some selection bias in our study, which is hospital based rather than population based. Although LHON has been reported to have a strong negative impact on quality of life, as indicated by the VF-14 index, our longitudinal study showed improvement in QoL in patients with LHON over time.

We showed that the VF-14 score at 6 months was significantly correlated with visual acuity at baseline. This is inconsistent with the study of Kirkman et al (1) that found LHON patients with G11778A or G3460A mutation had a significantly lower mean VF-14 score (21.8 ± 17.9) than patients with the T14484C mutation (44.2 ± 25.7) who often experience spontaneous vision improvement. The VF-14 scores of our patients at all 3 follow-up time points (18.0 ± 19.2, 19.9 ± 20.0, and 20.7 ± 20.2, respectively) were all lower than the patients with T14484C mutation. This further supports the observation that poor visual acuity is related to poor visual-related daily function.

The overall VF-14 scores in our patients were significantly increased at 1-year and 3-year follow-ups compared with the 6-month result. Although the median increase of VF-14 scores from the 6-month to 3-year follow-up was small (2.1), we found that QoL improvements (an increase of ≥4 points of VF-14) were related to early onset of the disease (<14 years old). It has been reported that younger patients with LHON (especially those younger than 10 years) have a higher chance of vision recovery (7–9). However, Lam et al (10) conducted a prospective observational study in patients with LHON with the G11778A mutation and reported that spontaneous improvement of visual acuity is not common in individuals with this genetic mutation. Although Garcia et al (11) found that profound vision loss in patients with LHON is associated with significant negative psychological and psychosocial effects, younger age may be associated with a higher potential for psychological adaption and coping. Putting these results and our findings together, the improvement of QoL may be due to a greater ability of adaptation in younger patients than vision acuity improvement. More follow-up data are needed to further clarify this possibility.

Results of subitem analysis of our patient cohort showed some similarities with those of Kirkman et al (1), specifically that reading small print and newspapers or books were activities of daily living that caused the greatest subjective difficulty and did not show any improvement. Significant differences between the 2 studies were playing board games, playing sports, and cooking, with our patients having lower scores. These differences may be due to the fact that all our patients had G11778A mutation that caused worse visual function while those of Kirkman et al included a patient with T14484C mutation who achieved better vision recovery. In addition, none of our patients received visual rehabilitation, but this was available in the study by Kirkman et al.

There are limitations to our study. First, we only collected and analyzed the correlation of patients' visual acuity at baseline with the improvement of QoL. Because the medical system in China is not well established, we were unable to remeasure visual function at follow-up visits. Second, we did not assess other factors that affect QoL including social and economic status, educational level, family involvement, and psychological status (11,12). Third, visual fields may change over time, especially when measured with microperimetry (13,14). These data were not obtained in our study.

Nevertheless, we conducted the first prospective longitudinal study of vision-related quality of life in LHON patients with the G11778A mutation in China and showed that patients, particularly young patients, can have spontaneous improvement in vision-related QoL. Hopefully, this improvement could be augmented with visual and occupational rehabilitation and psychological counseling.

ACKNOWLEDGMENTS

The authors thank ophthalmologists Lijuan Liu and Wenbin Wei, who refer LHON patients to our Neuro-Ophthalmology clinic.

REFERENCES

1. Kirkman MA, Korsten A, Leonhardt M, Dimitriadis K, De Coo IF, Klopstock T, Griffiths PG, Hudson G, Chinnery PF, Yu-Wai-Man P. Quality of life in patients with Leber hereditary optic neuropathy. Invest Ophthalmol Vis Sci. 2009;50:3112–3115.
2. Khadka J, Huang J, Mollazadegan K, Gao R, Chen H, Zhang S, Wang Q, Pesudovs K. Translation, cultural adaptation, and Rasch analysis of the visual function (VF-14) questionnaire. Invest Ophthalmol Vis Sci. 2014;55:4413–4420.
3. Liu X, Yin S, Liu Y. Revision and evaluation of visual function index scale (VF-14). Int Eye Sci. 2011;11:455–458.
4. Yen MY, Wang AG, Chang WL, Hsu WM, Liu JH, Wei YH. Leber's hereditary optic neuropathy-the spectrum of mitochondrial DNA mutations in Chinese patients. Jpn J Ophthalmol. 2002;46:45–51.
5. Mashima Y, Yamada K, Wakakura M, Kigasawa K, Kodoh J, Shimizu N, Oguchi Y. Spectrum of pathogenic mitochondrial DNA mutations and clinical features in Japanese families with Leber's hereditary optic neuropathy. Curr Eye Res. 1998;17:403–408.
6. Cui G, Ding H, Xu Y, Li B, Wang DW. Applications of the method of high resolution melting analysis for diagnosis of Leber's disease and the three primary mutation spectrum of LHON in the Han Chinese population. Gene. 2014;512:108–112.
7. Yu-Wai-Man P, Votruba M, Moore AT, Chinnery PF. Treatment strategies for inherited optic neuropathies: past, present and future. Eye. 2014;28:521–537.
8. Nakamura M, Yamamoto M. Variable pattern of visual recovery of Leber's hereditary optic neuropathy. Br J Ophthalmol. 2000;84:534–535.
9. Barboni P, Savini G, Valentino ML, La Morgia C, Bellusci C, De Negri AM, Sadun F, Carta A, Carbonelli M, Sadun AA, Carelli V. Leber's hereditary optic neuropathy with childhood onset. Invest Ophthalmol Vis Sci. 2006;47:5303–5309.
10. Lam BL, Feuer WJ, Schiffman JC, Porciatti V, Vandenbroucke R, Rosa PR, Gregori G, Guy J. Trial end points and natural history in patients with G11778A Leber hereditary optic neuropathy: preparation for gene therapy clinical trial. JAMA Ophthalmol. 2014;132:428–436.
11. Garcia GA, Khoshnevis M, Gale J, Frousiakis SE, Hwang TJ, Poincenot L, Karanjia R, Baron D, Sadun AA. Profound vision loss impairs psychological well-being in young and middle-aged individuals. Clin Ophthalmol. 2017;11:417–427.
12. Gale J, Khoshnevis M, Frousiakis SE, Karanjia R, Poincenot L, Sadun AA, Baron DA. An international study of emotional response to bilateral vision loss using a novel graphical online assessment tool. Psychosomatics. 2017;58:38–45.
13. Yanagisawa M, Kato S, Kobayashi M, Watanabe M, Ochiai M. Relationship between vision-related quality of life and different types of existing visual fields in Japanese patients. Int Ophthalmol. 2012;32:523–529.
14. Schönbach EM, Wolfson Y, Strauss RW, Ibrahim MA, Kong X, Muñoz B, Birch DG, Cideciyan AV, Hahn GA, Nittala M, Sunness JS. Macular sensitivity measured with microperimetry in Stargardt disease in the progression of atrophy secondary to stargardt disease (ProgStar) study: report no. 7. JAMA Ophthalmol. 2017;135:696–703.

Supplemental Digital Content

Copyright © 2018 by North American Neuro-Ophthalmology Society