Vision In Stroke cohort: Profile overview of visual impairment

Abstract Aim To profile the full range of visual disorders from a large prospective observation study of stroke survivors referred by stroke multidisciplinary teams to orthoptic services with suspected visual problems. Methods Multicenter prospective study undertaken in 20 acute Trust hospitals. Standardized screening/referral forms and investigation forms documented data on referral signs and symptoms plus type and extent of visual impairment. Results Of 1,345 patients referred with suspected visual impairment, 915 were recruited (59% men; mean age at stroke onset 69 years [SD 14]). Initial visual assessment was at median 22 days post stroke onset. Eight percent had normal visual assessment. Of 92% with confirmed visual impairment, 24% had reduced central visual acuity <0.3 logMAR and 13.5% <0.5 logMAR. Acquired strabismus was noted in 16% and acquired ocular motility disorders in 68%. Peripheral visual field loss was present in 52%, most commonly homonymous hemianopia. Fifteen percent had visual inattention and 4.6% had other visual perceptual disorders. Overall 84% were visually symptomatic with visual field loss the most common complaint followed by blurred vision, reading difficulty, and diplopia. Treatment options were provided to all with confirmed visual impairment. Targeted advice was most commonly provided along with refraction, prisms, and occlusion. Conclusions There are a wide range of visual disorders that occur following stroke and, frequently, with visual symptoms. There are equally a wide variety of treatment options available for these individuals. All stroke survivors require screening for visual impairment and warrant referral for specialist assessment and targeted treatment specific to the type of visual impairment.

Many visual impairments cause visual symptoms with stroke survivors aware of blurred/altered vision or jumbled/double images. These visual symptoms cause impact to general function and to daily life . However, a wide variety of interventions are available to aid and/or ameliorate these symptoms (Pollock et al., 2011a(Pollock et al., , 2011b(Pollock et al., , 2012.
The purpose of this study was to profile the full range of visual disorders from a large, prospective, observation cohort study of stroke survivors with suspected visual impairment, referred by stroke multidisciplinary teams to orthoptic services.

| Study design and population
This prospective multicenter observational case cohort study comprised local orthoptic principal investigators from 20 UK hospital trusts responsible for assessing stroke patients and collecting patient data. Orthoptic services for stroke units in the UK provide comprehensive visual assessment at the bedside and typically initiate management options at this acute stage. Review visits continue on the stroke unit as needed and, subsequently, in out-patient eye clinics.
The data were collated centrally at the University of Liverpool. The study had multicenter ethical approval via the National Research Ethics Service (06/Q0904/5) and was undertaken in accordance with the Tenets of Helsinki.
The target population was stroke patients suspected of having a visual difficulty. Referrals could be made from in-patient wards, rehabilitation units, community services, or out-patient clinics. Patients were given an information sheet and recruited after informed, written consent. Patients were excluded if they were unable to consent due to cognitive impairment, unwilling to consent, if their diagnosis was that of transient ischemic attack or if they were discharged without vision assessment.

| Measures
Patients with suspected visual difficulty were identified using a screening form (Figure 1: SPSS: RRID: SCR_002865). Subsequently this was used as the referral form to the Orthoptic service. A standardized investigation sheet was used for the eye assessment consisting of identification of known preexistent ocular pathology, symptoms and signs, investigation of visual field, ocular motility, and perceptual aspects (Rowe, 2011). Visual fields were assessed qualitatively by traditional confrontation methods or quantitatively by Humphrey (Humphrey systems, Dublin, CA, USA) automated central and/or peripheral static perimetry or Goldmann/Octopus (Haag Streit Int, Switzerland) kinetic perimetry.
Visual acuity was assessed uniocularly at near and distance fixation with Snellen or logMAR acuity tests. Low visual acuity was considered in two categories. The first defined low visual acuity as less than best corrected 6/12 Snellens acuity or 0.3 logMAR in accordance with UK driving standards. The second defined low visual acuity as less than 6/18 Snellens acuity or 0.5 logMAR and equal or better than 3/60 Snellens acuity as per World Health Organisation (WHO) guidelines.
Assessment of ocular alignment and motility consisted of cover test, evaluation of saccadic, smooth pursuit and vergence eye movements, retinal correspondence (Bagolini glasses), fusional vergence (20D or fusional range), stereopsis (Frisby near test), prism cover test, and lid and pupil function.
Perceptual deficits were recorded after questioning of the patient and/or carers and relatives. Inattention was assessed by means of a combination of assessments including line bisection, Albert's test, cancellation tests, and memory tests using verbal description and drawing. Alexia was diagnosed where patients described an inability to read (despite being able to see the text) because of being unable to decipher the words or their meaning or being unable to make sense of the text. Stroke details were recorded from patient notes accounting for stroke laterality, type, and area involved. Ocular treatment details were recorded along with outcome. Reasons for nonattendance at review appointments included death, a move out of area, lost to follow-up, follow-up unwanted, or unknown.

| Data analysis
Results were inputted to the statistical package SPSS version 22 (IBM SPSS Statistics, USA). Pearson chi squared test (x 2 ) was undertaken to analyze cross tabulations of results for visual field loss and outcome of follow-up versus factors such as age, presence of other visual impairment, laterality, and area of stroke and recovery. A t test was used to analyze differences between similar measurements with normal distributions, for example, strabismus.

| General demographics
One thousand three hundred and forty-five patients were referred for visual assessment for this study. All were suspected of having visual problems. Nine hundred and fifteen patients were recruited and 430 patients were excluded. Reasons for exclusion included inability/unwilling to provide informed, written consent as required of the ethical approval for this study (n = 259), patients were discharged prior to receiving visual assessment (n = 52), diagnosis was changed to transient ischemic attack or other pathology (n = 54), patients died prior to visual assessment (n = 26), or patients failed to attend for visual assessment (n = 4). It was not possible to obtain full visual information on these excluded patients.
Of 915 patients recruited, 59% (n = 540) were men and 41% (n = 375) women. Mean age at onset of stroke was 69 years (range 1-94: SD 14 years). One patient was aged 1 year and the range thereafter was 19-94 years. The median age at onset of stroke was 71 years.
Median duration from onset of stroke to initial baseline eye examination was 22 days (0-2543 days), the mean of 40.84 (SD 141.28) days being skewed by three outliers who were referred a number of years after the stroke onset. Stroke lesion was right sided in 448 patients (49%, i.e., right sided brain), left sided in 348 (38%), and bilateral in 119 (13%). Infarcts accounted for 773 cases (84.5%) with the remainder due to hemorrhage.

| Ocular alignment and movement
Manifest strabismus was noted in 18.5% (n = 169) patients of which 3% was long-standing prior to the stroke onset (Table 2A). Acquired constant exotropia occurred most frequently, p = .001.
Normal convergence near point of 6 cm was reported in nearly 39% of patients (n = 354). Reduced near point of convergence less than 8 cm was recorded in nearly 38% (n = 345) and for less than 10 cm in 26.7% (n = 235).

| Lid and pupil function
Normal lid function was evident in 85.9% (n = 786). The remainder had unilateral or bilateral ptosis or lid retraction, with unilateral ptosis being most common ( 90.8% (n = 831) with the remainder having varied forms of dilated or miosed pupils (Table 3B). Relative afferent pupillary defect and anisocoria were the most common forms.

| Visual field loss and visual perception
Over half (52.3%, n = 479) of patients had visual field loss ( Table 4). The most common type of visual field loss was found to be complete (n = 259) and partial (n = 79) homonymous hemianopia and occurring significantly more frequently to the left side than to the right side or bilaterally, p = .001 (t test). Other types included superior or inferior quadrantanopia (n = 73), constricted visual fields (n = 44), scotomas (n = 5), temporal crescent defect (n = 1), and bilateral hemianopia (cortical blindness: n = 1).
Visual inattention was noted in 15% of the cohort (n = 137) whereas other visual perceptual deficits such as visual agnosia, cortical color visual or depth impairment, and acquired alexia were noted in 4.6%.

| Management
Treatment options were offered to all patients with visual impairment (92%:

| Impact to activities of daily living
Activities of daily living dependent on vision were assessed for patients with and without visual symptoms (Figure 2). There was no significant difference between groups, p = .447 (Pearson x 2 test).

| DISCUSSION
This study comprised a subpopulation of stroke survivors; those referred with suspected visual impairment. A high percentage of stroke survivors were subsequently confirmed as having visual impairment (92%). Types of visual impairment included visual field loss, ocular motility disorders, reduced central visual acuity, and visual perceptual disorders. Visual impairment most likely to be new and due to the stroke included visual field loss, ocular motility disorders, and visual perceptual disorders. Complete homonymous hemianopia was the most common form of visual field loss with partial hemianopia and quadrantanopia visual field defects also occurring frequently.
Saccadic dysmetria was the most common form of ocular motility disorder with other frequently occurring disorders including cranial nerve palsy, gaze palsy, strabismus, reduced near point of convergence, and nystagmus. As expected, visual inattention was the most commonly occurring visual perceptual disorders but, in addition, patients were noted to report cortical impairment of color perception or depth, alexia, and visual agnosia. Fifty stroke survivors had normal visual assessment and were visually asymptomatic but, potentially, these may previously have been visually symptomatic but had Clearly, focused investigation is required to confirm the diagnosis of many of these disorders, particularly those with more subtle presentation features. Visual symptoms were reported overall by 84% of patients but of a wide variety as reported previously (Rowe, 2013).
Notably, of 16% who were asymptomatic, many had confirmed visual impairment including substantial hemianopic visual field loss, limited eye movements, and reduced visual acuity. This latter group raises the question of how many stroke survivors with visual impairment may remain undetected where formal vision screening is not undertaken.
This study only recruited those referred with suspected visual impairment and used a screening/referral form to facilitate this. However, as published previously, issues exist with such screening forms particularly where there is reliance on patient-reported visual symptoms to aid identification of suspected visual impairment (Rowe, 2011). It remains unknown how many patients with visual impairment were undetected because of patient failure to report visual symptoms either because of communication, cognitive, or other failure to notify staff/carers of their symptoms and visual difficulties. Only specialist widespread visual screening of all stroke survivors will aid capture of such cases.
Given that poststroke visual impairment is estimated at 65% (Hepworth et al., 2015) and in view of the confirmed unmet needs reported by stroke survivors with visual impairment  there is an urgent requirement to implement comprehensive, wide-spread screening of stroke survivors to ensure identification of their visual issues. National guidance exists for provision of specialist services on stroke units for poststroke visual impairment with orthoptists being recommended as part of the core acute stroke unit team (British Irish Orthoptic Society, 2016;Intercollegiate Stroke Working Party, 2016); services that are proven to be feasible and acceptable for delivery on acute stroke units and neuro-rehabilitation units and which are cost effective (Pollock, Hazelton, & Brady, 2011;. Recent research reports vision screening to be achievable at a median of 3 days post stroke with full visual examinations achieved at a median of 4 days post stroke (Rowe, Hepworth, Hanna, & Howard, 2016).

The impact of visual impairment is clear with considerable issues
relating to driving, activities of daily living, mobilization, social engagement among others . Given the high rate of visual symptoms and known impact, access to appropriate management options at the early acute poststroke stage is important. A wide variety of management options were provided in this study, many of which are evidence based as to their efficacy (Adler, 2002;Carruthers, Kennedy, & Bagaric, 1990;Firth & Whittle, 1994;Pollock et al., 2011Pollock et al., , 2011aPollock et al., , 2011bPollock et al., , 2012Thurtell & Leigh, 2010). It is important to note that, for advice on compensatory mechanisms, these are frequently of benefit to patients despite lacking an evidence base through case control or randomized trials. It is of further importance to recognize these management options are not 'one size fits all' but require targeting to the type of visual impairment and individual symptoms. Ensuring referral to specialist services will direct the stroke survivor to correct and appropriate treatment, whilst minimizing risks from inappropriate therapies provided by staff lacking the requisite training and/or knowledge.

| CONCLUSIONS
The Vision In Stroke study is, to our knowledge, the first large-scale observation study of poststroke visual impairment. In this population of stroke survivors referred with suspected visual impairment, prevalence of visual impairment was 92%. There are a wide range of visual disorders that occur following stroke and, frequently, give rise to visual symptoms. There are equally a wide variety of treatment options available for these individuals. We recommend that all stroke survivors require screening for visual impairment in the early days poststroke onset and warrant referral for specialist assessment and targeted treatment specific to the type of visual impairment.