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Vision related quality of life in spinocerebellar ataxia
JNS-14135; No of Pages 5 Journal of the Neurological Sciences xxx (2015) xxx–xxx
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Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Vision related quality of life in spinocerebellar ataxia Sachin Kedar a,b,⁎, Deepta Ghate b, Earnest L. Murray c, James J. Corbett d, S.H. Subramony e a
Department of Neurology, University of Nebraska Medical Center, Omaha, NE, USA Department of Ophthalmology and Visual Sciences, Stanley Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, USA c Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA d Department of Neurology and Ophthalmology, University of Mississippi Medical Center, Jackson, MS, USA e Department of Neurology and the McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA b
a r t i c l e
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Article history: Received 27 March 2015 Received in revised form 6 October 2015 Accepted 7 October 2015 Available online xxxx Keywords: Spinocerebellar ataxia Quality of life Ocular motility Nystagmus Diplopia Vision
a b s t r a c t Objective: Spinocerebellar ataxia (SCA) leads to abnormal ocular motility and alignment. The objective of this study was to quantitatively assess vision, ocular motility and alignment and its impact on vision related quality of life (VRQOL) in SCA. Methods: Nineteen genetically diagnosed SCA subjects (11 SCA type 3, 3 SCA type 1 and 5 SCA type 6) participated at two university centers. All subjects completed the National Eye Institute Visual Function Questionnaire (NEI-VFQ), 10-Item Neuro-Ophthalmic Supplement (NOS), scale for assessment and rating of ataxia (SARA) and ophthalmic examination. Twelve subjects seen at one of the 2 sites underwent quantitative ocular motility and alignment assessment. Results: Composite scores for NEI-VFQ (mean 76.3 ± 13) and NOS (mean 65.2 ± 16.8) were significantly decreased in SCA subjects. NEI-VFQ subscale scores were decreased for general, near, distance and peripheral vision and driving. SCA patients had decreased low contrast sensitivity, stereoacuity and multiple ocular motility defects which included gaze limitation (9/12), nystagmus (5/12), distance esophoria (11/12), near exophoria (12/12) and receded near point of convergence. A significant negative correlation was noted between composite scores and distance convergence fusional amplitude. Conclusion: VRQOL is significantly decreased in SCA compared to normal population. All SCA patients should be screened for visual disability and referred for neuro-ophthalmic assessment promptly. © 2015 Elsevier B.V. All rights reserved.
1. Introduction The spinocerebellar ataxias (SCA) are dominantly inherited neurodegenerative diseases characterized by very gradual evolution of cerebellar ataxia and other neurological deficits. SCA are phenotypically and genotypically heterogeneous with more than 30 identified genetic types [1]. Besides SCA-7, which causes rod-cone dystrophy, other SCA types are not associated with defects of afferent visual pathways [2]. Disorders of eye movement, alignment and gaze stability are prevalent in SCA which leads to diplopia, blurred vision and oscillopsia [3,4]. Visual symptoms appear early and often precede neurological
Abbreviations: SCA, spinocerebellar ataxia; NEI VFQ, National Eye Institute Visual Function Questionnaire; NOS, neuro-ophthalmic supplement; VRQOL, vision related quality of life; SARA, scale for assessment and rating of ataxia; ETDRS, early treatment diabetic retinopathy study; Log MAR, logarithm of minimum angle of resolution; PD, prism diopters; SD, standard deviation. ⁎ Corresponding author at: 988440 Nebraska Medical Center, Omaha, NE 68198-8440, USA. E-mail addresses: [email protected] (S. Kedar), [email protected] (D. Ghate), [email protected] (E.L. Murray), [email protected] (J.J. Corbett), [email protected]fl.edu (S.H. Subramony).
deficits by several years [5]. The impact of ophthalmological abnormalities on quality of life in SCA is not known. The objective of this study is to assess vision related quality of life measures in SCA and correlate with disease duration, severity and neuro-ophthalmologic abnormalities.
2. Methods Subjects were recruited from the neurology clinics at two large centers with dedicated facilities to care for patients with ataxia. The study adhered to the tenets of Declaration of Helsinki and was approved by the institutional review board at both centers. The study design was cross-sectional. Patients were eligible to participate if they had molecularly proven SCA types 1, 2, 3 and 6, had a compatible phenotype for the disease, were of age 18 years or older and agreed to participate in this study. Subjects with alternative causes for ataxia, unrelated ocular pathology or history of amblyopia and strabismus were excluded. Strabismus (also known as “crossed eyes” or “squint”) was defined as a disorder where the two eyes do not line up in the same direction. Informed consent for participation was obtained from all patients.
http://dx.doi.org/10.1016/j.jns.2015.10.013 0022-510X/© 2015 Elsevier B.V. All rights reserved.
Please cite this article as: S. Kedar, et al., Vision related quality of life in spinocerebellar ataxia, J Neurol Sci (2015), http://dx.doi.org/10.1016/ j.jns.2015.10.013
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2.1. Clinical methods Ophthalmological (SK, DG) and neurological examinations (SHS, ELM) were performed by masked investigators. The details of neurological examination, SARA score (scale for assessment and rating of ataxia), functional score and assessment of ambulation using Step activity monitor have previously been described for this cohort in a separate publication [6]. 2.1.1. Visual function questionnaire The National Eye Institute Visual Function Questionnaire—Version 2000 (NEI-VFQ; developed by RAND; funded by NEI, Baltimore, MD) and 10-question Neuro-Ophthalmic Supplement (NOS) were administered and scored using standard guidelines and compared with established normal data [7–9]. The NEI-VFQ comprises a set of 25 vision related questions (representing 11 vision related domains) in addition to a single question pertaining to general health rating. Instructions for questionnaire administration, scoring of patient responses, generation of subscale and composite scores and statistical power computation are described in the NEI-VFQ manual [8]. The NOS is a supplement to the NEI-VFQ and includes 10 items specific to neuro-ophthalmological presentations. The instructions for administration and scoring of NOS, which is similar to the NEI-VFQ, are described in an online supplement to the original publication by the authors of the questionnaire [7]. Items on both NEI-VFQ and NOS are presented in a Likert scale and subjects are asked to rate symptom severity and difficulty performing vision related tasks. The subject responses are then scored on a 0–100 scale and used to generate subscale and composite scores for statistical analysis. 2.1.2. Ophthalmological procedures The following ophthalmological procedures were performed for all patients. Distance visual acuity was measured using Revised 2000 Series ETDRS Charts (Precision Vision, La Salle, Illinois) in a retro-illuminated cabinet at 4 m. Monocular as well as binocular testing was performed using available refractive correction. The total number of letters read correctly in each row was recorded and converted to the log MAR value using established guidelines [10]. Near acuity was tested using Rosenbaum near vision card at 14 in Snellen equivalent of the smallest row of letters read correctly was recorded. Low contrast letter acuity was tested with retro-illuminated 1.25% and 2.5% Sloan Translucent Low Contrast Charts (Precision Vision, La Salle, Illinois) using available correction in binocular state at distance of 2 m. Letters read correctly in each row was recorded and the total number of letters was used for statistical analysis by comparing with established control data [11]. Testing was done in a binocular state because none of our patients demonstrated interocular differences for distance and near acuity and we had excluded patients with ophthalmological diseases that could affect vision. Color vision was tested using Roth 28- Hue test (Richmond Products, Albuquerque, NM). Each subject was asked to sort the color caps in a circular sequence starting with the reference color cap. The sequence of the color caps as sorted by the subject was recorded on the score sheet provided by the manufacturer. Color vision was considered normal if there were two or fewer sorting errors and sequence line did not cross the center [12]. Stereo-acuity was tested using Randot test (Stereo Optical Co. Inc., Chicago IL) at 40 cm and recorded as arc-seconds (normal ≤ 40 s) [13,14]. Confrontation visual field was performed using a 5 mm circular red target to assess the kinetic boundary and Amsler grid to assess the central field [15,16]. Examination of ocular motility and alignment was performed on twelve patients seen at site one by an experienced neuroophthalmologist (SK). Seven subjects evaluated at the second site did not undergo this examination due to lack of expertise. The range of ocular motility was assessed by observing the corneal and scleral light reflex during horizontal and vertical gaze with the penlight kept at a distance of 25 cm from the nasion. Adduction was considered normal
if 1/3rd of adducting cornea extended beyond an imaginary line from the superior to inferior puncta; abduction was normal if corneo-scleral limbus extended to lateral canthus. Vertical versions were normal if supraducted eye demonstrated a corneal light reflex beyond the pupillary margin and infraducted eye demonstrated scleral reflex, 10 mm superior to limbus [17]. Cover-uncover and prism tests were used to study ocular alignment and fusional amplitudes. The following were used as abnormal values for fusional amplitudes: divergence b5 prism diopters, convergence b15 prism diopters at 20 ft; convergence and divergence b20 prism diopters at 25 cm [18]. Near point of convergence was measured using Krimsky accommodation rule (Richmond Products, Albuquerque, NM) and was normal if ≤10 cm [17].
2.2. Statistical analysis Statistical analysis was performed using IBM SPSS statistics Version 19. Outcome measures were composite and subscale score on NEI VFQ and NOS. Summary data included mean and standard deviations for continuous variables and frequency tables for categorical variables. Bivariate analysis was performed to evaluate factors that influenced scores on NEI visual function questionnaire and neuro-ophthalmic supplement questionnaire. Independent samples t-test was used for group comparisons. Multivariate analysis was not performed due to small sample size.
3. Results Nineteen subjects (15 females; 4 males) were enrolled. The cohort included 11 SCA type 3, 3 SCA type1 and 5 SCA type 6. No eligible SCA type 2 subjects were found. The mean age of the cohort was 56.16 ± 10.66 (SD) years and the mean disease duration was 9.05 ± 6.18 (SD) years. Table 1 summarizes disease severity and visual measures (n = 19). The mean age at examination was 56.16 years (SD 10.66; range 38–75 years); the mean age at onset was 47.16 years (SD 10.63; range 23–63 years). The mean disease duration was 9.05 years (SD 6.18; range 2–24 years). Ten patients (52.7%) were ambulating independently while nine (47.3%) needed wheelchair assistance or cane at the time of study assessment.
3.1. Neuro-ophthalmological findings Table 1 provides a summary of the ataxia scores (SARA score and functional score) as well as ophthalmological measures. Distance visual acuity was better than 20/40 in all subjects while near acuity with correction was 20/25 Snellen equivalent or better in all patients. Low contrast sensitivity was significantly reduced in SCA (p b 0.001 independent samples t-test) compared to the established normal reference [11]. The values for contrast sensitivity were less than 2 SD in 11 subjects for the 2.5% chart and 8 subjects for the 1.25% contrast sensitivity chart compared to established normal reference. Color vision was normal in all except one patient who demonstrated a pre-existing tritan defect. Stereo acuity was normal in 7/19 (36.8%) subjects. Visual field testing by confrontation method was normal in all patients. The results for the ocular motility and alignment performed in 12 subjects are listed in Table 1. All 12 subjects had more than 1 abnormality of ocular movement and/or alignment. Gaze limitation was observed in 9/12 patients. Distance convergence fusional amplitude was decreased in 10/12 patients while distance divergence fusional amplitude was decreased in 6/12 patients. Near convergence and divergence fusional amplitudes were decreased in 10/12 (83%) and 8/12 (67%) patients respectively. Nystagmus was observed in 5/12 patients and all had end-gaze nystagmus. None of these patients complained of oscillopsia and all had visual acuity 20/25 or better.
Please cite this article as: S. Kedar, et al., Vision related quality of life in spinocerebellar ataxia, J Neurol Sci (2015), http://dx.doi.org/10.1016/ j.jns.2015.10.013
S. Kedar et al. / Journal of the Neurological Sciences xxx (2015) xxx–xxx Table 1 Summary of the neurological and ophthalmological findings in patients with spinocerebellar ataxia. Parameter Ambulating without assistance SARA score Functional stage Distance visual acuity (logMAR values) Mean ± SD Low contrast acuity (binocular testing; number of letters read)
Stereo-acuity (seconds) Ocular motility defects
Ocular alignment at 20 ft
Ocular alignment at 25 cm
Near point convergence
10/19 (53%) Mean: 16.71 ± 6.29 (SD), range 8–34 Mean 3.29 ± 1.00 (SD), range 1.5–5.0 Right eye: 0.063 ± 0.17 (SD) Left eye: 0.08 ± 0.21 (SD) Binocular: −0.02 ± 0.17 (SD) 1.25%: Mean19.84 ± 2.60 (SD) 2.5%: 28.37 ± 8.58 (SD) Normal controls12: 1.25%: 34 ± 8 (SD); n = 324 2.5%; 43 ± 6 (SD); n = 324 Normal (≤40 s): 7/19 Mean: 55 ± 22.79 (SD) seconds, range 30–100 s Gaze limitation: 9/12 (horizontal limitation: 2; Vertical: 4; both: 3) Nystagmus: 5/12 Esophoria: 11/12: Mean: 4.09 ± 3.5 (SD) prism diopters Exophoria: 1/12: 4 prism diopters Decreased convergence amplitude (b15 pd): 8/12 Mean 13.42 ± 7.96 (SD) prism diopters; Decreased divergence amplitude (b5 pd): 6/12 Mean: 8.75 ± 7.40 (SD) prism diopters; Exophoria: 12/12; Mean: 7.58 ± 5.14 (SD) prism diopters Decreased convergence amplitude (b20 pd): 10/12 Mean 10.67 ± 6.77 (SD) prism diopters Decreased divergence amplitude (b20 pd):8/12 Mean: 16.17 ± 5.81 (SD) prism diopters Mean 28.7 ± 12.83 (SD) cm (SD 12.83)
SARA: scale for the assessment and rating of ataxia. SD: standard deviation. logMAR: logarithm of minimal angle of resolution. PD: prism diopters; cm: centimeter.
specific subscales (role difficulties, dependency, social functioning and mental health) as well as the composite score. Composite score on the NOS for SCA was also significantly worse compared to normal population. There was good correlation between NEI VFQ and NOS composite scores (r2 = 0.733; p = 0.000).
3.3. Factors influencing the outcome measures Table 3 is a presentation of the factors that influenced scores on the different sub-scales of the NEI-VFQ and NOS. There was no correlation between composite scores on both questionnaires with disease duration, neurological severity (SARA score and functional stage) or afferent visual parameters (visual acuity, low contrast scores, color vision, and stereo acuity). Distance convergence fusional amplitude showed significant and negative correlation with composite scores on both NEI-VFQ (r = −0.605; p = 0.03) and NOS (r = −0.57; p = 0.05). Multivariate analysis was not performed due to the small sample size. Due to small numbers we are unable to ascertain if nystagmus affected quality of life significantly.
Table 3 Factors affecting composite and subscale scores on the National Eye Institute visual function questionnaire and neuro-ophthalmic supplement using bivariate analysis. Only those factors which achieved statistical significance (p b 0.05) are included. NEI subscales
Variables with significant correlation
General health General vision Near vision Distance vision Driving Peripheral vision Color vision
None None None None None None None Age onset (r = −0.47; p = 0.04) Disease duration (r = −0.50; p = 0.03) Ocular misalignment at distance (r = +0.647; p = 0.02) Distance convergence fusional amplitudes (r = −0.747; p = 0.005) None None None Distance convergence fusional amplitudes (r = −0.605; p = 0.03)
3.2. Quality of life measures Ocular pain
The NEI VFQ composite and subscale as well as the NOS composite scores for SCA subjects and previously established normal population are provided in Table 2. SCA subjects had significantly poor scores compared to normal population in the following NEI VFQ subscales: general vision, near vision, distance vision, driving, peripheral vision, vision
Table 2 Visual function questionnaire composite and subscale scores in spinocerebellar ataxia and established controls. NEI-visual function questionnaire subscales General health General vision Near vision Distance vision Driving Peripheral vision Color vision Ocular pain Role difficulties Dependency Social functioning Mental health Composite score
Neuro-ophthalmic supplement composite score NEI: National Eye Institute.
Study population (n = 19) Mean (SD) 59.2 (26.6) 70.5 (13.9) 74.6 (16.1) 71.5 (21.0) 42.9 (17.4) 59.2 (27.9) 96.1 (12.5) 86.2 (15.0) 79.2 (21.9) 86.4 (20.5) 90.8 (12.4) 78.0 (22.5) 76.3 (13)
65.23 (16.80)
Reference population (n = 122) Mean (SD) 69 (24) 83 (15) 92 (13) 93 (11) 87 (18) 97 (10) 98 (8) 90 (15) 93 (13) 99 (6) 99 (3) 92 (12) 93 (13) 93 (7) Reference population (N = 65)
p Value (2-tailed t-test) 0.1 0.001 0.0002 0.0003 b0.0001 b0.0001 0.5 0.3 0.01 0.02 0.01 0.02 b0.0001
b0.0001
3
Role difficulties Dependency Social functioning Mental health Composite score Neuro-ophthalmic supplement
Difficulty when eyes tired Difficulty in bright sunlight
Difficulty parking car Difficulty using computer Eyes see differently Unusual eye/lid appearance Blurry vision Difficulty focusing moving objects Binocular diplopia Ptosis Composite score
Ocular misalignment at distance (r = +0.622; p = 0.03) Distance convergence fusional amplitudes (r = −0.575; p = 0.05) Distance convergence fusional amplitudes (r = −0.713;p = 0.009) Age at onset (r = −0.50; p = 0.03) Age at examination (r = −0.57; p = 0.01) SARA score (r = −0.548; p = 0.015) 2.5% Contrast sensitivity (r = +0.532; p = 0.02) 2.5% Contrast sensitivity (r = +0.522; p = 0.02) None 2.5% contrast sensitivity (r = +0.47; p = 0.02) Disease duration (r = +0.46; p = 0.05) None None None Convergence fusional amplitudes (r = −0.57; p = 0.05)
NEI-VFQ: National Eye Institute Visual Function Questionnaire.
Please cite this article as: S. Kedar, et al., Vision related quality of life in spinocerebellar ataxia, J Neurol Sci (2015), http://dx.doi.org/10.1016/ j.jns.2015.10.013
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4. Discussion To the best of our knowledge, this is the only study of vision related quality of life (VRQOL) measures in SCA. We have shown that VRQOL is significantly decreased in subjects with SCA compared to normal population. Very few studies have evaluated health related quality of life (HRQOL) in SCA. In a cross-sectional study of 84 SCA subjects in Spain, the authors found that the HRQOL (as measured by the EQ-5D) was significantly lower in SCA compared to scores for the general population or subjects with chronic diseases such as stroke or HIV/AIDS. [19]. We have also shown that SCA leads to decreased contrast sensitivity and stereo-acuity in addition to multiple deficits of eye movement and alignment. SCA subjects had decreased contrast sensitivity despite normal visual acuity and color vision. Decreased low contrast sensitivity has been described in other neurological conditions such as Parkinson's disease and multiple sclerosis but not SCA. Decreased contrast sensitivity may be secondary to altered retinal dopaminergic synaptic activity in Parkinson's disease [20,21], and loss of retinal ganglion cells and retinal nerve fiber layer (RNFL) in multiple sclerosis [11,22,23]. The mechanism of contrast sensitivity loss in SCA is yet to be established. Retinal abnormalities that have been described in small case series of SCA include thinning of the peripapillary RNFL in SCA-2 and 3 and thinning of the perifoveal macula in SCA-1, 3 and 6 [24]. Progressive decrease in RNFL was seen in 4 SCA-3 patients over a mean follow up period of 14.25 months [25]. How SCA produces retinal abnormalities is unclear, with no supportive evidence for primary retinal pathology except in SCA-7. Abnormal eye movement and alignment were seen in all 12 subjects and included near exophoria (100%), distance esophoria (92%), convergence insufficiency (83%), gaze limitation (75%) and nystagmus (42%). There is abundant literature on eye movement deficits in SCA. Irregular pursuit, dysmetric saccades, nystagmus, slow eye movement velocity and horizontal ophthalmoparesis are well known in all SCA phenotypes [4,26–29]. In a bedside examination of the eye movements in 301 subjects with SCA from 12 centers, Moscovich et al. reported finding gaze evoked nystagmus, abnormalities of saccades and smooth pursuits, horizontal and vertical gaze limitation and square wave jerks in their patients. They report that ophthalmoparesis was the least common oculomotor abnormality and correlated well with higher SARA scores and poor functional stage [4]. Remote near point of convergence, horizontal nystagmus, and pathological saccadic interruption of pursuit movements were reported in another series of SCA-1, 3 and 5 [3]. We believe that VRQOL in SCA is affected by defects of ocular motility and alignment. Although our study is limited by the small number of SCA subjects, especially those who underwent examination of eye movement and alignment, we found that composite scores on both questionnaires showed a significant and negative correlation with distance convergence fusional amplitude. These results have been demonstrated by alternative methods by other researchers. Using synaptophore technique, Ohyagi et al. reported exotropia at near and esotropia for distance in SCA, which they believed was secondary to impaired vergence from supranuclear defects [30]. Similar abnormalities were seen in our cohort and support our hypothesis that changes of fusional amplitudes for distance and near diminish ability to maintain ocular alignment at various distances. While, this may explain some of the task difficulties reported by subjects with SCA on both questionnaires, we are unsure if the correlation is a statistical anomaly or related to disease pathology. We believe a larger scale study designed to investigate the influence of SCA on the fusional amplitudes and VRQOL is needed. Distance vision task difficulty was reported by 18/19 subjects with SCA on the NEI-VFQ. This may be secondary to esophoria and divergence insufficiency at 20 ft. Divergence insufficiency is frequently underreported in neurological diseases, likely due to the overwhelming importance of the other neurological deficits. In a series of patients with primary and secondary divergence insufficiency, Jacobson reports
2 patients with idiopathic cerebellar degeneration and progressive supranuclear palsy, while noting that “this association is generally not noted in either condition” [31]. Lack of correlation between this subscale score and the amount of distance esophoria and divergence amplitudes and VRQOL measures might be due to the small sample size in our study. Near vision task difficulties on NEI VFQ were reported by 17/19 subjects with SCA, despite normal near acuity. We believe that difficulty with near vision tasks might be the result of convergence insufficiency, seen in 10/12 subjects who had the motility examination. It is well known that convergence insufficiency leads to diplopia, visual blurring, asthenopia and headache [32,33]. Difficulty with peripheral vision was reported by 16/19 subjects in our cohort despite having normal visual field examination. We believe this might be related to horizontal gaze limitation and slow saccades, which is perceived by the SCA patient as limitation of peripheral vision. Our study has limitations inherent to a small sample size observational study. The sample size was small due to strict inclusion criteria which required genetic confirmation in a relatively rare genetic condition. Although we showed that SCA subjects had significant decrease of the VRQOL scores on both questionnaires, we were unable to clearly identify visual and neurological factors that might have contributed to the decreased scores by using multivariate statistical methods. A second limitation of our study is the use of confrontation methods rather than standardized perimetry for visual field assessment. We used a combination of confrontation techniques which are sensitive (74%) and specific (90%) in detecting visual field defects [15,34]. All visual field assessments were done by experts in glaucoma and neuro-ophthalmology. 5. Conclusion In conclusion, our study shows that VRQOL measures are significantly lower in SCA compared to the normal population. SCA subjects were found to have multiple abnormalities of the visual system which included decreased low contrast sensitivity, stereo-acuity and multiple abnormalities of ocular motility and alignment. These defects likely impair daily activities at near and distance such as reading or driving which compounds the significant disability caused by the neurological deficits. Several treatment modalities for defects of ocular motility and alignment are currently available. These include optimization of vision by refractive correction, vision rehabilitation to enhance convergence and divergence, diplopia relief using prisms and strabismus surgery and medication trials for management of nystagmus. We recommend that all patients with SCA be screened for visual complaints. Early recognition and referral of patients with visual complaints to neuroophthalmology service should be considered by all physicians who care for patients with SCA. Authorship Sachin Kedar performed the study concept and design, acquisition of data, analysis of data, statistical analysis, study supervision, and drafting/revising article for content. Deepta Ghate performed theacquisition of data, statistical analysis, and drafting/revising article for content. Earnest L. Murray performed the acquisition of data and drafting/ revising article for content. James Corbett performed the drafting/revising article for content and study supervision. S.H. Subramony performed the study concept and design, acquisition of data, analysis of data, study supervision and coordination, obtaining funding, and drafting/revising article for content. Financial disclosure Dr. Kedar received royalty for editorial services from Elsevier Inc. Dr. Ghate reports no financial disclosures.
Please cite this article as: S. Kedar, et al., Vision related quality of life in spinocerebellar ataxia, J Neurol Sci (2015), http://dx.doi.org/10.1016/ j.jns.2015.10.013
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Dr. Murray reports no financial disclosures. Dr. Corbett reports no financial disclosures. Dr. Subramony serves on the Speaker bureau for Athena diagnostics and receives research support from Friedreich Ataxia Research Alliance, Muscular Dystrophy Association, NIH grant no. 1R21AG044449-01A1, ISIS pharmaceuticals and Reatta pharmaceuticals. Acknowledgements Study funding: Study was supported by Luckyday Foundation, Jackson, MS. References [1] H.L. Paulson, Dominantly inherited ataxias: lessons learned from Machado–Joseph disease/spinocerebellar ataxia type 3, Semin. Neurol. 27 (2007) 133–142. [2] G. Garden, Spinocerebellar Ataxia Type 7, 1993. [3] J.S. Durig, J.C. Jen, J.L. Demer, Ocular motility in genetically defined autosomal dominant cerebellar ataxia, Am J. Ophthalmol. 133 (2002) 718–721. [4] M. Moscovich, M.S. Okun, C. Favilla, K.P. Figueroa, S.M. Pulst, S. Perlman, G. Wilmot, C. Gomez, J. Schmahmann, H. Paulson, V. Shakkottai, S. Ying, T. Zesiewicz, S.H. Kuo, P. Mazzoni, K. Bushara, G. Xia, T. Ashizawa, S.H. Subramony, Clinical evaluation of eye movements in spinocerebellar ataxias: a prospective multicenter study, J. Neuroophthalmol. 35 (2015) 16–21. [5] C. Globas, S.T. du Montcel, L. Baliko, S. Boesch, C. Depondt, S. DiDonato, A. Durr, A. Filla, T. Klockgether, C. Mariotti, B. Melegh, M. Rakowicz, P. Ribai, R. Rola, T. Schmitz-Hubsch, S. Szymanski, D. Timmann, B.P. Van de Warrenburg, P. Bauer, L. Schols, Early symptoms in spinocerebellar ataxia type 1, 2, 3, and 6, Mov. Disord. 23 (2008) 2232–2238. [6] S.H. Subramony, S. Kedar, E. Murray, E. Protas, H. Xu, T. Ashizawa, A. Tan, Objective home-based gait assessment in spinocerebellar ataxia, J. Neurol. Sci. 313 (2012) 95–98. [7] B.A. Raphael, K.M. Galetta, D.A. Jacobs, C.E. Markowitz, G.T. Liu, M.L. Nano-Schiavi, S.L. Galetta, M.G. Maguire, C.M. Mangione, D.R. Globe, L.J. Balcer, Validation and test characteristics of a 10-item neuro-ophthalmic supplement to the NEI-VFQ-25, Am J. Ophthalmol. 142 (2006) 1026–1035. [8] C.M. Mangione, The National Eye Institute 25-item Visual Function Questionnaire (VFQ-25): version 2000, Scoring Manual, 2000 2000, p. 2013. [9] C.M. Mangione, P.P. Lee, P.R. Gutierrez, K. Spritzer, S. Berry, R.D. Hays, Development of the 25-item National Eye Institute Visual Function Questionnaire, Arch. Ophthalmol. 119 (2001) 1050–1058. [10] J.T. Holladay, Visual acuity measurements, J. Cataract Refract. Surg. 30 (2004) 287–290. [11] R.E. Sakai, D.J. Feller, K.M. Galetta, S.L. Galetta, L.J. Balcer, Vision in multiple sclerosis: the story, structure-function correlations, and models for neuroprotection, J. Neuroophthalmol. 31 (2011) 362–373. [12] A.J. Adams, R. Rodic, R. Husted, R. Stamper, Spectral sensitivity and color discrimination changes in glaucoma and glaucoma-suspect patients, Invest. Ophthalmol. Vis. Sci. 23 (1982) 516–524. [13] E. Birch, C. Williams, J. Drover, V. Fu, C. Cheng, K. Northstone, M. Courage, R. Adams, Randot Preschool Stereoacuity Test: normative data and validity, J. AAPOS 12 (2008) 23–26. [14] S.Y. Lee, N.K. Koo, Change of stereoacuity with aging in normal eyes, Korean J. Ophthalmol. 19 (2005) 136–139.
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Please cite this article as: S. Kedar, et al., Vision related quality of life in spinocerebellar ataxia, J Neurol Sci (2015), http://dx.doi.org/10.1016/ j.jns.2015.10.013
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Vision related quality of life in spinocerebellar ataxia Sachin Kedar a,b,⁎, Deepta Ghate b, Earnest L. Murray c, James J. Corbett d, S.H. Subramony e a
Department of Neurology, University of Nebraska Medical Center, Omaha, NE, USA Department of Ophthalmology and Visual Sciences, Stanley Truhlsen Eye Institute, University of Nebraska Medical Center, Omaha, NE, USA c Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA d Department of Neurology and Ophthalmology, University of Mississippi Medical Center, Jackson, MS, USA e Department of Neurology and the McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA b
a r t i c l e
i n f o
Article history: Received 27 March 2015 Received in revised form 6 October 2015 Accepted 7 October 2015 Available online xxxx Keywords: Spinocerebellar ataxia Quality of life Ocular motility Nystagmus Diplopia Vision
a b s t r a c t Objective: Spinocerebellar ataxia (SCA) leads to abnormal ocular motility and alignment. The objective of this study was to quantitatively assess vision, ocular motility and alignment and its impact on vision related quality of life (VRQOL) in SCA. Methods: Nineteen genetically diagnosed SCA subjects (11 SCA type 3, 3 SCA type 1 and 5 SCA type 6) participated at two university centers. All subjects completed the National Eye Institute Visual Function Questionnaire (NEI-VFQ), 10-Item Neuro-Ophthalmic Supplement (NOS), scale for assessment and rating of ataxia (SARA) and ophthalmic examination. Twelve subjects seen at one of the 2 sites underwent quantitative ocular motility and alignment assessment. Results: Composite scores for NEI-VFQ (mean 76.3 ± 13) and NOS (mean 65.2 ± 16.8) were significantly decreased in SCA subjects. NEI-VFQ subscale scores were decreased for general, near, distance and peripheral vision and driving. SCA patients had decreased low contrast sensitivity, stereoacuity and multiple ocular motility defects which included gaze limitation (9/12), nystagmus (5/12), distance esophoria (11/12), near exophoria (12/12) and receded near point of convergence. A significant negative correlation was noted between composite scores and distance convergence fusional amplitude. Conclusion: VRQOL is significantly decreased in SCA compared to normal population. All SCA patients should be screened for visual disability and referred for neuro-ophthalmic assessment promptly. © 2015 Elsevier B.V. All rights reserved.
1. Introduction The spinocerebellar ataxias (SCA) are dominantly inherited neurodegenerative diseases characterized by very gradual evolution of cerebellar ataxia and other neurological deficits. SCA are phenotypically and genotypically heterogeneous with more than 30 identified genetic types [1]. Besides SCA-7, which causes rod-cone dystrophy, other SCA types are not associated with defects of afferent visual pathways [2]. Disorders of eye movement, alignment and gaze stability are prevalent in SCA which leads to diplopia, blurred vision and oscillopsia [3,4]. Visual symptoms appear early and often precede neurological
Abbreviations: SCA, spinocerebellar ataxia; NEI VFQ, National Eye Institute Visual Function Questionnaire; NOS, neuro-ophthalmic supplement; VRQOL, vision related quality of life; SARA, scale for assessment and rating of ataxia; ETDRS, early treatment diabetic retinopathy study; Log MAR, logarithm of minimum angle of resolution; PD, prism diopters; SD, standard deviation. ⁎ Corresponding author at: 988440 Nebraska Medical Center, Omaha, NE 68198-8440, USA. E-mail addresses: [email protected] (S. Kedar), [email protected] (D. Ghate), [email protected] (E.L. Murray), [email protected] (J.J. Corbett), [email protected]fl.edu (S.H. Subramony).
deficits by several years [5]. The impact of ophthalmological abnormalities on quality of life in SCA is not known. The objective of this study is to assess vision related quality of life measures in SCA and correlate with disease duration, severity and neuro-ophthalmologic abnormalities.
2. Methods Subjects were recruited from the neurology clinics at two large centers with dedicated facilities to care for patients with ataxia. The study adhered to the tenets of Declaration of Helsinki and was approved by the institutional review board at both centers. The study design was cross-sectional. Patients were eligible to participate if they had molecularly proven SCA types 1, 2, 3 and 6, had a compatible phenotype for the disease, were of age 18 years or older and agreed to participate in this study. Subjects with alternative causes for ataxia, unrelated ocular pathology or history of amblyopia and strabismus were excluded. Strabismus (also known as “crossed eyes” or “squint”) was defined as a disorder where the two eyes do not line up in the same direction. Informed consent for participation was obtained from all patients.
http://dx.doi.org/10.1016/j.jns.2015.10.013 0022-510X/© 2015 Elsevier B.V. All rights reserved.
Please cite this article as: S. Kedar, et al., Vision related quality of life in spinocerebellar ataxia, J Neurol Sci (2015), http://dx.doi.org/10.1016/ j.jns.2015.10.013
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2.1. Clinical methods Ophthalmological (SK, DG) and neurological examinations (SHS, ELM) were performed by masked investigators. The details of neurological examination, SARA score (scale for assessment and rating of ataxia), functional score and assessment of ambulation using Step activity monitor have previously been described for this cohort in a separate publication [6]. 2.1.1. Visual function questionnaire The National Eye Institute Visual Function Questionnaire—Version 2000 (NEI-VFQ; developed by RAND; funded by NEI, Baltimore, MD) and 10-question Neuro-Ophthalmic Supplement (NOS) were administered and scored using standard guidelines and compared with established normal data [7–9]. The NEI-VFQ comprises a set of 25 vision related questions (representing 11 vision related domains) in addition to a single question pertaining to general health rating. Instructions for questionnaire administration, scoring of patient responses, generation of subscale and composite scores and statistical power computation are described in the NEI-VFQ manual [8]. The NOS is a supplement to the NEI-VFQ and includes 10 items specific to neuro-ophthalmological presentations. The instructions for administration and scoring of NOS, which is similar to the NEI-VFQ, are described in an online supplement to the original publication by the authors of the questionnaire [7]. Items on both NEI-VFQ and NOS are presented in a Likert scale and subjects are asked to rate symptom severity and difficulty performing vision related tasks. The subject responses are then scored on a 0–100 scale and used to generate subscale and composite scores for statistical analysis. 2.1.2. Ophthalmological procedures The following ophthalmological procedures were performed for all patients. Distance visual acuity was measured using Revised 2000 Series ETDRS Charts (Precision Vision, La Salle, Illinois) in a retro-illuminated cabinet at 4 m. Monocular as well as binocular testing was performed using available refractive correction. The total number of letters read correctly in each row was recorded and converted to the log MAR value using established guidelines [10]. Near acuity was tested using Rosenbaum near vision card at 14 in Snellen equivalent of the smallest row of letters read correctly was recorded. Low contrast letter acuity was tested with retro-illuminated 1.25% and 2.5% Sloan Translucent Low Contrast Charts (Precision Vision, La Salle, Illinois) using available correction in binocular state at distance of 2 m. Letters read correctly in each row was recorded and the total number of letters was used for statistical analysis by comparing with established control data [11]. Testing was done in a binocular state because none of our patients demonstrated interocular differences for distance and near acuity and we had excluded patients with ophthalmological diseases that could affect vision. Color vision was tested using Roth 28- Hue test (Richmond Products, Albuquerque, NM). Each subject was asked to sort the color caps in a circular sequence starting with the reference color cap. The sequence of the color caps as sorted by the subject was recorded on the score sheet provided by the manufacturer. Color vision was considered normal if there were two or fewer sorting errors and sequence line did not cross the center [12]. Stereo-acuity was tested using Randot test (Stereo Optical Co. Inc., Chicago IL) at 40 cm and recorded as arc-seconds (normal ≤ 40 s) [13,14]. Confrontation visual field was performed using a 5 mm circular red target to assess the kinetic boundary and Amsler grid to assess the central field [15,16]. Examination of ocular motility and alignment was performed on twelve patients seen at site one by an experienced neuroophthalmologist (SK). Seven subjects evaluated at the second site did not undergo this examination due to lack of expertise. The range of ocular motility was assessed by observing the corneal and scleral light reflex during horizontal and vertical gaze with the penlight kept at a distance of 25 cm from the nasion. Adduction was considered normal
if 1/3rd of adducting cornea extended beyond an imaginary line from the superior to inferior puncta; abduction was normal if corneo-scleral limbus extended to lateral canthus. Vertical versions were normal if supraducted eye demonstrated a corneal light reflex beyond the pupillary margin and infraducted eye demonstrated scleral reflex, 10 mm superior to limbus [17]. Cover-uncover and prism tests were used to study ocular alignment and fusional amplitudes. The following were used as abnormal values for fusional amplitudes: divergence b5 prism diopters, convergence b15 prism diopters at 20 ft; convergence and divergence b20 prism diopters at 25 cm [18]. Near point of convergence was measured using Krimsky accommodation rule (Richmond Products, Albuquerque, NM) and was normal if ≤10 cm [17].
2.2. Statistical analysis Statistical analysis was performed using IBM SPSS statistics Version 19. Outcome measures were composite and subscale score on NEI VFQ and NOS. Summary data included mean and standard deviations for continuous variables and frequency tables for categorical variables. Bivariate analysis was performed to evaluate factors that influenced scores on NEI visual function questionnaire and neuro-ophthalmic supplement questionnaire. Independent samples t-test was used for group comparisons. Multivariate analysis was not performed due to small sample size.
3. Results Nineteen subjects (15 females; 4 males) were enrolled. The cohort included 11 SCA type 3, 3 SCA type1 and 5 SCA type 6. No eligible SCA type 2 subjects were found. The mean age of the cohort was 56.16 ± 10.66 (SD) years and the mean disease duration was 9.05 ± 6.18 (SD) years. Table 1 summarizes disease severity and visual measures (n = 19). The mean age at examination was 56.16 years (SD 10.66; range 38–75 years); the mean age at onset was 47.16 years (SD 10.63; range 23–63 years). The mean disease duration was 9.05 years (SD 6.18; range 2–24 years). Ten patients (52.7%) were ambulating independently while nine (47.3%) needed wheelchair assistance or cane at the time of study assessment.
3.1. Neuro-ophthalmological findings Table 1 provides a summary of the ataxia scores (SARA score and functional score) as well as ophthalmological measures. Distance visual acuity was better than 20/40 in all subjects while near acuity with correction was 20/25 Snellen equivalent or better in all patients. Low contrast sensitivity was significantly reduced in SCA (p b 0.001 independent samples t-test) compared to the established normal reference [11]. The values for contrast sensitivity were less than 2 SD in 11 subjects for the 2.5% chart and 8 subjects for the 1.25% contrast sensitivity chart compared to established normal reference. Color vision was normal in all except one patient who demonstrated a pre-existing tritan defect. Stereo acuity was normal in 7/19 (36.8%) subjects. Visual field testing by confrontation method was normal in all patients. The results for the ocular motility and alignment performed in 12 subjects are listed in Table 1. All 12 subjects had more than 1 abnormality of ocular movement and/or alignment. Gaze limitation was observed in 9/12 patients. Distance convergence fusional amplitude was decreased in 10/12 patients while distance divergence fusional amplitude was decreased in 6/12 patients. Near convergence and divergence fusional amplitudes were decreased in 10/12 (83%) and 8/12 (67%) patients respectively. Nystagmus was observed in 5/12 patients and all had end-gaze nystagmus. None of these patients complained of oscillopsia and all had visual acuity 20/25 or better.
Please cite this article as: S. Kedar, et al., Vision related quality of life in spinocerebellar ataxia, J Neurol Sci (2015), http://dx.doi.org/10.1016/ j.jns.2015.10.013
S. Kedar et al. / Journal of the Neurological Sciences xxx (2015) xxx–xxx Table 1 Summary of the neurological and ophthalmological findings in patients with spinocerebellar ataxia. Parameter Ambulating without assistance SARA score Functional stage Distance visual acuity (logMAR values) Mean ± SD Low contrast acuity (binocular testing; number of letters read)
Stereo-acuity (seconds) Ocular motility defects
Ocular alignment at 20 ft
Ocular alignment at 25 cm
Near point convergence
10/19 (53%) Mean: 16.71 ± 6.29 (SD), range 8–34 Mean 3.29 ± 1.00 (SD), range 1.5–5.0 Right eye: 0.063 ± 0.17 (SD) Left eye: 0.08 ± 0.21 (SD) Binocular: −0.02 ± 0.17 (SD) 1.25%: Mean19.84 ± 2.60 (SD) 2.5%: 28.37 ± 8.58 (SD) Normal controls12: 1.25%: 34 ± 8 (SD); n = 324 2.5%; 43 ± 6 (SD); n = 324 Normal (≤40 s): 7/19 Mean: 55 ± 22.79 (SD) seconds, range 30–100 s Gaze limitation: 9/12 (horizontal limitation: 2; Vertical: 4; both: 3) Nystagmus: 5/12 Esophoria: 11/12: Mean: 4.09 ± 3.5 (SD) prism diopters Exophoria: 1/12: 4 prism diopters Decreased convergence amplitude (b15 pd): 8/12 Mean 13.42 ± 7.96 (SD) prism diopters; Decreased divergence amplitude (b5 pd): 6/12 Mean: 8.75 ± 7.40 (SD) prism diopters; Exophoria: 12/12; Mean: 7.58 ± 5.14 (SD) prism diopters Decreased convergence amplitude (b20 pd): 10/12 Mean 10.67 ± 6.77 (SD) prism diopters Decreased divergence amplitude (b20 pd):8/12 Mean: 16.17 ± 5.81 (SD) prism diopters Mean 28.7 ± 12.83 (SD) cm (SD 12.83)
SARA: scale for the assessment and rating of ataxia. SD: standard deviation. logMAR: logarithm of minimal angle of resolution. PD: prism diopters; cm: centimeter.
specific subscales (role difficulties, dependency, social functioning and mental health) as well as the composite score. Composite score on the NOS for SCA was also significantly worse compared to normal population. There was good correlation between NEI VFQ and NOS composite scores (r2 = 0.733; p = 0.000).
3.3. Factors influencing the outcome measures Table 3 is a presentation of the factors that influenced scores on the different sub-scales of the NEI-VFQ and NOS. There was no correlation between composite scores on both questionnaires with disease duration, neurological severity (SARA score and functional stage) or afferent visual parameters (visual acuity, low contrast scores, color vision, and stereo acuity). Distance convergence fusional amplitude showed significant and negative correlation with composite scores on both NEI-VFQ (r = −0.605; p = 0.03) and NOS (r = −0.57; p = 0.05). Multivariate analysis was not performed due to the small sample size. Due to small numbers we are unable to ascertain if nystagmus affected quality of life significantly.
Table 3 Factors affecting composite and subscale scores on the National Eye Institute visual function questionnaire and neuro-ophthalmic supplement using bivariate analysis. Only those factors which achieved statistical significance (p b 0.05) are included. NEI subscales
Variables with significant correlation
General health General vision Near vision Distance vision Driving Peripheral vision Color vision
None None None None None None None Age onset (r = −0.47; p = 0.04) Disease duration (r = −0.50; p = 0.03) Ocular misalignment at distance (r = +0.647; p = 0.02) Distance convergence fusional amplitudes (r = −0.747; p = 0.005) None None None Distance convergence fusional amplitudes (r = −0.605; p = 0.03)
3.2. Quality of life measures Ocular pain
The NEI VFQ composite and subscale as well as the NOS composite scores for SCA subjects and previously established normal population are provided in Table 2. SCA subjects had significantly poor scores compared to normal population in the following NEI VFQ subscales: general vision, near vision, distance vision, driving, peripheral vision, vision
Table 2 Visual function questionnaire composite and subscale scores in spinocerebellar ataxia and established controls. NEI-visual function questionnaire subscales General health General vision Near vision Distance vision Driving Peripheral vision Color vision Ocular pain Role difficulties Dependency Social functioning Mental health Composite score
Neuro-ophthalmic supplement composite score NEI: National Eye Institute.
Study population (n = 19) Mean (SD) 59.2 (26.6) 70.5 (13.9) 74.6 (16.1) 71.5 (21.0) 42.9 (17.4) 59.2 (27.9) 96.1 (12.5) 86.2 (15.0) 79.2 (21.9) 86.4 (20.5) 90.8 (12.4) 78.0 (22.5) 76.3 (13)
65.23 (16.80)
Reference population (n = 122) Mean (SD) 69 (24) 83 (15) 92 (13) 93 (11) 87 (18) 97 (10) 98 (8) 90 (15) 93 (13) 99 (6) 99 (3) 92 (12) 93 (13) 93 (7) Reference population (N = 65)
p Value (2-tailed t-test) 0.1 0.001 0.0002 0.0003 b0.0001 b0.0001 0.5 0.3 0.01 0.02 0.01 0.02 b0.0001
b0.0001
3
Role difficulties Dependency Social functioning Mental health Composite score Neuro-ophthalmic supplement
Difficulty when eyes tired Difficulty in bright sunlight
Difficulty parking car Difficulty using computer Eyes see differently Unusual eye/lid appearance Blurry vision Difficulty focusing moving objects Binocular diplopia Ptosis Composite score
Ocular misalignment at distance (r = +0.622; p = 0.03) Distance convergence fusional amplitudes (r = −0.575; p = 0.05) Distance convergence fusional amplitudes (r = −0.713;p = 0.009) Age at onset (r = −0.50; p = 0.03) Age at examination (r = −0.57; p = 0.01) SARA score (r = −0.548; p = 0.015) 2.5% Contrast sensitivity (r = +0.532; p = 0.02) 2.5% Contrast sensitivity (r = +0.522; p = 0.02) None 2.5% contrast sensitivity (r = +0.47; p = 0.02) Disease duration (r = +0.46; p = 0.05) None None None Convergence fusional amplitudes (r = −0.57; p = 0.05)
NEI-VFQ: National Eye Institute Visual Function Questionnaire.
Please cite this article as: S. Kedar, et al., Vision related quality of life in spinocerebellar ataxia, J Neurol Sci (2015), http://dx.doi.org/10.1016/ j.jns.2015.10.013
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4. Discussion To the best of our knowledge, this is the only study of vision related quality of life (VRQOL) measures in SCA. We have shown that VRQOL is significantly decreased in subjects with SCA compared to normal population. Very few studies have evaluated health related quality of life (HRQOL) in SCA. In a cross-sectional study of 84 SCA subjects in Spain, the authors found that the HRQOL (as measured by the EQ-5D) was significantly lower in SCA compared to scores for the general population or subjects with chronic diseases such as stroke or HIV/AIDS. [19]. We have also shown that SCA leads to decreased contrast sensitivity and stereo-acuity in addition to multiple deficits of eye movement and alignment. SCA subjects had decreased contrast sensitivity despite normal visual acuity and color vision. Decreased low contrast sensitivity has been described in other neurological conditions such as Parkinson's disease and multiple sclerosis but not SCA. Decreased contrast sensitivity may be secondary to altered retinal dopaminergic synaptic activity in Parkinson's disease [20,21], and loss of retinal ganglion cells and retinal nerve fiber layer (RNFL) in multiple sclerosis [11,22,23]. The mechanism of contrast sensitivity loss in SCA is yet to be established. Retinal abnormalities that have been described in small case series of SCA include thinning of the peripapillary RNFL in SCA-2 and 3 and thinning of the perifoveal macula in SCA-1, 3 and 6 [24]. Progressive decrease in RNFL was seen in 4 SCA-3 patients over a mean follow up period of 14.25 months [25]. How SCA produces retinal abnormalities is unclear, with no supportive evidence for primary retinal pathology except in SCA-7. Abnormal eye movement and alignment were seen in all 12 subjects and included near exophoria (100%), distance esophoria (92%), convergence insufficiency (83%), gaze limitation (75%) and nystagmus (42%). There is abundant literature on eye movement deficits in SCA. Irregular pursuit, dysmetric saccades, nystagmus, slow eye movement velocity and horizontal ophthalmoparesis are well known in all SCA phenotypes [4,26–29]. In a bedside examination of the eye movements in 301 subjects with SCA from 12 centers, Moscovich et al. reported finding gaze evoked nystagmus, abnormalities of saccades and smooth pursuits, horizontal and vertical gaze limitation and square wave jerks in their patients. They report that ophthalmoparesis was the least common oculomotor abnormality and correlated well with higher SARA scores and poor functional stage [4]. Remote near point of convergence, horizontal nystagmus, and pathological saccadic interruption of pursuit movements were reported in another series of SCA-1, 3 and 5 [3]. We believe that VRQOL in SCA is affected by defects of ocular motility and alignment. Although our study is limited by the small number of SCA subjects, especially those who underwent examination of eye movement and alignment, we found that composite scores on both questionnaires showed a significant and negative correlation with distance convergence fusional amplitude. These results have been demonstrated by alternative methods by other researchers. Using synaptophore technique, Ohyagi et al. reported exotropia at near and esotropia for distance in SCA, which they believed was secondary to impaired vergence from supranuclear defects [30]. Similar abnormalities were seen in our cohort and support our hypothesis that changes of fusional amplitudes for distance and near diminish ability to maintain ocular alignment at various distances. While, this may explain some of the task difficulties reported by subjects with SCA on both questionnaires, we are unsure if the correlation is a statistical anomaly or related to disease pathology. We believe a larger scale study designed to investigate the influence of SCA on the fusional amplitudes and VRQOL is needed. Distance vision task difficulty was reported by 18/19 subjects with SCA on the NEI-VFQ. This may be secondary to esophoria and divergence insufficiency at 20 ft. Divergence insufficiency is frequently underreported in neurological diseases, likely due to the overwhelming importance of the other neurological deficits. In a series of patients with primary and secondary divergence insufficiency, Jacobson reports
2 patients with idiopathic cerebellar degeneration and progressive supranuclear palsy, while noting that “this association is generally not noted in either condition” [31]. Lack of correlation between this subscale score and the amount of distance esophoria and divergence amplitudes and VRQOL measures might be due to the small sample size in our study. Near vision task difficulties on NEI VFQ were reported by 17/19 subjects with SCA, despite normal near acuity. We believe that difficulty with near vision tasks might be the result of convergence insufficiency, seen in 10/12 subjects who had the motility examination. It is well known that convergence insufficiency leads to diplopia, visual blurring, asthenopia and headache [32,33]. Difficulty with peripheral vision was reported by 16/19 subjects in our cohort despite having normal visual field examination. We believe this might be related to horizontal gaze limitation and slow saccades, which is perceived by the SCA patient as limitation of peripheral vision. Our study has limitations inherent to a small sample size observational study. The sample size was small due to strict inclusion criteria which required genetic confirmation in a relatively rare genetic condition. Although we showed that SCA subjects had significant decrease of the VRQOL scores on both questionnaires, we were unable to clearly identify visual and neurological factors that might have contributed to the decreased scores by using multivariate statistical methods. A second limitation of our study is the use of confrontation methods rather than standardized perimetry for visual field assessment. We used a combination of confrontation techniques which are sensitive (74%) and specific (90%) in detecting visual field defects [15,34]. All visual field assessments were done by experts in glaucoma and neuro-ophthalmology. 5. Conclusion In conclusion, our study shows that VRQOL measures are significantly lower in SCA compared to the normal population. SCA subjects were found to have multiple abnormalities of the visual system which included decreased low contrast sensitivity, stereo-acuity and multiple abnormalities of ocular motility and alignment. These defects likely impair daily activities at near and distance such as reading or driving which compounds the significant disability caused by the neurological deficits. Several treatment modalities for defects of ocular motility and alignment are currently available. These include optimization of vision by refractive correction, vision rehabilitation to enhance convergence and divergence, diplopia relief using prisms and strabismus surgery and medication trials for management of nystagmus. We recommend that all patients with SCA be screened for visual complaints. Early recognition and referral of patients with visual complaints to neuroophthalmology service should be considered by all physicians who care for patients with SCA. Authorship Sachin Kedar performed the study concept and design, acquisition of data, analysis of data, statistical analysis, study supervision, and drafting/revising article for content. Deepta Ghate performed theacquisition of data, statistical analysis, and drafting/revising article for content. Earnest L. Murray performed the acquisition of data and drafting/ revising article for content. James Corbett performed the drafting/revising article for content and study supervision. S.H. Subramony performed the study concept and design, acquisition of data, analysis of data, study supervision and coordination, obtaining funding, and drafting/revising article for content. Financial disclosure Dr. Kedar received royalty for editorial services from Elsevier Inc. Dr. Ghate reports no financial disclosures.
Please cite this article as: S. Kedar, et al., Vision related quality of life in spinocerebellar ataxia, J Neurol Sci (2015), http://dx.doi.org/10.1016/ j.jns.2015.10.013
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Please cite this article as: S. Kedar, et al., Vision related quality of life in spinocerebellar ataxia, J Neurol Sci (2015), http://dx.doi.org/10.1016/ j.jns.2015.10.013