Visual pigment concentration and photoreceptor outer segment length in the human retina.

PURPOSE: The Beer-Lambert law suggests that visual pigment optical density (OD) should be linearly related to the length of photoreceptor outer segments (POSs). Mammalian studies indicate that visual pigment concentration increases with POS length, but the nature of this relationship may vary due to factors such as visual pigment packing density or retinal eccentricity, and may not necessarily be linearly related. The purpose of this study was to establish the relationship between OD and POS length in humans. METHODS: Spectral domain optical coherence tomography (OCT) was used to image POS, and imaging retinal densitometry (IRD) was used to measure OD at corresponding locations in 19 healthy participants (age range 25-82 years). POS length and OD measurements were extracted from OCT and IRD images at 23 discrete locations spanning the central 9° of the retina. The averaged data from all participants were fitted with models based on the Beer-Lambert law to establish the relationship between OD and POS length. RESULTS: Visual pigment OD increased monotonically with POS length, but the relationship was non-linear, and a straight-line fit, based on a simple interpretation of the Beer-Lambert law, provided a poor description. A model allowing for different rod and cone visual pigment concentrations provided a superior fit. Specifically, the data were well described by a model where the molar concentration of visual pigment in cones and rods were 3.8 × 10-3 mol/L and 1.8 × 10-3mol/L, respectively. CONCLUSIONS: In accordance with the Beer-Lambert law, the results indicate that OD increases monotonically with POS length in humans, but the precise relationship is dependent on photoreceptor type. These results suggest that visual pigment concentration in rods is only about 48% of that found in cones. This may be due to the ubiquitous nature of artificial light that works to reduce the concentration of rhodopsin in rod photoreceptors.

Ability of Head-Mounted Display Technology to Improve Mobility in People With Low Vision: A Systematic Review.

Purpose: The purpose of this study was to undertake a systematic literature review on how vision enhancements, implemented using head-mounted displays (HMDs), can improve mobility, orientation, and associated aspects of visual function in people with low vision. Methods: The databases Medline, Chinl, Scopus, and Web of Science were searched for potentially relevant studies. Publications from all years until November 2018 were identified based on predefined inclusion and exclusion criteria. The data were tabulated and synthesized to produce a systematic review. Results: The search identified 28 relevant papers describing the performance of vision enhancement techniques on mobility and associated visual tasks. Simplifying visual scenes improved obstacle detection and object recognition but decreased walking speed. Minification techniques increased the size of the visual field by 3 to 5 times and improved visual search performance. However, the impact of minification on mobility has not been studied extensively. Clinical trials with commercially available devices recorded poor results relative to conventional aids. Conclusions: The effects of current vision enhancements using HMDs are mixed. They appear to reduce mobility efficiency but improved obstacle detection and object recognition. The review highlights the lack of controlled studies with robust study designs. To support the evidence base, well-designed trials with larger sample sizes that represent different types of impairments and real-life scenarios are required. Future work should focus on identifying the needs of people with different types of vision impairment and providing targeted enhancements. Translational Relevance: This literature review examines the evidence regarding the ability of HMD technology to improve mobility in people with sight loss.

The Effect of Systemic Hyperoxia and Hypoxia on Scotopic Thresholds in People with Early and Intermediate Age-related Macular Degeneration.

Purpose: Morphological retinal changes combined with functional evidence implicate hypoxia in the pathogenesis of age-related macular degeneration (AMD). However, the role of hypoxia in the scotopic threshold deficit reported in AMD has not been investigated. This study compared scotopic thresholds in participants with early and intermediate AMD recorded under conditions of systemic hypoxia, hyperoxia and normoxia. Materials and Methods: Over two sessions scotopic thresholds were measured with participants breathing 21% and 60% oxygen (n = 12 early AMD, n = 11 age-similar controls) or 21% and 14% oxygen (n = 16 early AMD, n = 20 age-similar controls). Thresholds were measured using a 'white', annular 12 degrees stimulus, using a QUEST procedure. Results: There was no statistically significant change in scotopic thresholds within the AMD or control group when breathing the hyperoxic gas mixture (60% oxygen) or the hypoxic gas mixture (14% oxygen) when compared to the normoxic condition (21% oxygen). There was also no statistically significant difference in scotopic thresholds between groups under the hyperoxic or hypoxic gas conditions. The difference between groups under the normoxic condition was not statistically significant for the hyperoxia study (p = .70), but did reach significance in the hypoxia study (p = .05). Conclusion: This study provided no evidence that breathing that breathing 14% or 60% oxygen altered scotopic thresholds in those with early AMD when compared to controls. However, the lack of elevated scotopic thresholds in the AMD group of the hyperoxia study is of note, as it is unlikely that hyperoxia would reduce thresholds which were not significantly raised at baseline, regardless of whether hypoxia was a factor in the disease pathogenesis. The findings of this study do not rule out a role for hypoxia in early AMD, but this needs to be assessed in future experiments using measures that differ significantly between people with AMD and controls.

Functional Imaging of the Outer Retinal Complex using High Fidelity Imaging Retinal Densitometry.

We describe a new technique, high fidelity Imaging Retinal Densitometry (IRD), which probes the functional integrity of the outer retinal complex. We demonstrate the ability of the technique to map visual pigment optical density and synthesis rates in eyes with and without macular disease. A multispectral retinal imaging device obtained precise measurements of retinal reflectance over space and time. Data obtained from healthy controls and 5 patients with intermediate AMD, before and after photopigment bleaching, were used to quantify visual pigment metrics. Heat maps were plotted to summarise the topography of rod and cone pigment kinetics and descriptive statistics conducted to highlight differences between those with and without AMD. Rod and cone visual pigment synthesis rates in those with AMD (v = 0.043 SD 0.019 min-1 and v = 0.119 SD 0.046 min-1, respectively) were approximately half those observed in healthy controls (v = 0.079 SD 0.024 min-1 for rods and v = 0.206 SD 0.069 min-1 for cones). By mapping visual pigment kinetics across the central retina, high fidelity IRD provides a unique insight into outer retinal complex function. This new technique will improve the phenotypic characterisation, diagnosis and treatment monitoring of various ocular pathologies, including AMD.

The Relationship Between the Photopic Negative Response and Retinal Ganglion Cell Topography.

Purpose: To assess the topographic relationship between the photopic negative response (PhNR) and retinal ganglion cell distribution in healthy individuals. Method: Data was recorded from 16 healthy participants. The amplitude of PhNRs obtained in response to focal long duration (250 ms) and brief flash (5 ms), red (660 nm) on blue (469 nm) stimuli of increasing size (5° - full field) were measured. The number of retinal ganglion cell receptive fields (RGCf) in each stimulus area was established from the literature and regression analysis used to determine the relationships between: PhNR amplitude and number of RGCfs stimulated, PhNR density and the RGCf density and response per RGCf as a function of eccentricity. Results: The overall amplitude of the PhNR increased with stimulus size and the response density declined from ∼0.1 µV/deg in the macular region to ∼0.003 µV/deg approximately 45° from the fovea. Contrary to expectations, the relationship between the PhNR and number of RGCf was nonlinear, the response from more eccentric neurons being about three times greater than those in the macular region. Conclusions: Although the amplitude of the PhNR broadly maps on to the topographic distribution of RGCf the increase in PhNR amplitude with increasing eccentricity is only partly explained by RGCf numbers. Increases in the PhNR amplitude may be due to topographic variations in the contributions from other non-RGC neurons, as well as eccentricity-related morphologic and physiologic differences in RGCs.

An automated segmentation approach to calibrating infantile nystagmus waveforms.

Infantile nystagmus (IN) describes a regular, repetitive movement of the eyes. A characteristic feature of each cycle of the IN eye movement waveform is a period in which the eyes are moving at minimal velocity. This so-called "foveation" period has long been considered the basis for the best vision in individuals with IN. In recent years, the technology for measuring eye movements has improved considerably, but there remains the challenge of calibrating the direction of gaze in tracking systems when the eyes are continuously moving. Identifying portions of the nystagmus waveform suitable for calibration typically involves time-consuming manual selection of the foveation periods from the eye trace. Without an accurate calibration, the exact parameters of the waveform cannot be determined. In this study, we present an automated method for segmenting IN waveforms with the purpose of determining the foveation positions to be used for calibration of an eye tracker. On average, the "point of regard" was found to be within 0.21° of that determined by hand-marking by an expert observer. This method enables rapid clinical quantification of waveforms and the possibility of gaze-contingent research paradigms being performed with this patient group.

Depressive symptoms in people with vision impairment: a cross-sectional study to identify who is most at risk.

OBJECTIVE: To identify the risk factors for significant depressive symptoms in people with visual impairment in England and Wales to provide information on who is most at risk and to whom support services could be targeted in future. DESIGN: A cross-sectional study using baseline data from a pragmatic randomised controlled trial. SETTING AND PARTICIPANTS: 990 participants aged 18 or over attending 1 of 14 low-vision rehabilitation primary care optometry-based clinics in South Wales or two hospital clinics in London. OUTCOME MEASURE: A score of ≥6 on the Geriatric Depression Scale-15 was classed as clinically significant depressive symptoms. RESULTS: In a multivariable logistic regression model, significant depressive symptoms were associated with age (adjusted OR (AOR)=0.82, 95% CI: 0.66 to 0.90, p<0.001), ethnicity (AOR non-white compared with white=1.72, 95% CI: 1.05 to 2.81, p=0.031), total number of eye conditions (AOR for two vs one condition=0.98, 95% CI: 0.67 to 1.43; three or more vs one condition=0.34, 95% CI: 0.15 to 0.75, p=0.026), self-reported health (AOR for excellent vs poor=0.01, 95% CI: 0.00 to 0.12; very good vs poor=0.06, 95% CI: 0.03 to 0.13; good vs poor=0.14, 95% CI: 0.08 to 0.24; fair vs poor=0.28, 95% CI: 0.18 to 0.46, p<0.001) and self-reported visual functioning (AOR=1.45, 95% CI: 1.31 to 1.61, p<0.001). CONCLUSION: Younger age, a non-white ethnicity, fewer eye conditions and poorer self-reported health and visual function are risk factors for significant depressive symptoms in this population. TRIAL REGISTRATION NUMBER: ISRCTN46824140; Pre-results.

An Evaluation of a Battery of Functional and Structural Tests as Predictors of Likely Risk of Progression of Age-Related Macular Degeneration.

Purpose: To evaluate the ability of visual function and structural tests to identify the likely risk of progression from early/intermediate to advanced AMD, using the Age-Related Eye Disease Study (AREDS) simplified scale as a surrogate for risk of progression. The secondary aim was to determine the relationship between disease severity grade and the observed functional and structural deficits. Methods: A total of 100 participants whose AMD status varied from early to advanced were recruited. Visual function was assessed using cone dark adaptation, 14 Hz flicker and chromatic threshold tests and retinal structure was assessed by measuring drusen volume and macular thickness. The predictive value of the tests was estimated using ordinal regression analysis. Group comparisons were assessed using analysis of covariance. Results: Change in cone dark adaptation (cone τ) and yellow-blue (YB) chromatic sensitivity were independent predictors for AMD progression risk (cone τ, pseudo R2 = 0.35, P < 0.001; YB chromatic threshold, pseudo R2 = 0.16, P < 0.001). The only structural predictor was foveal thickness (R2 = 0.05, P = 0.047). Chromatic sensitivity and cone dark adaptation were also the best functional tests at distinguishing between severity groups. Drusen characteristics clearly differentiated between participants with early and advanced disease, but were not able to differentiate between those with early AMD and controls. Mean differences in retinal thickness existed between severity groups at the foveal (P = 0.040) and inner (P = 0.001) subfields. Conclusions: This study indicates that cone τ, YB chromatic threshold and foveal thickness are independent predictors of likely risk of AMD progression.

Microperimetry in Age-Related Macular Degeneration: An Evidence-Base for Pattern Deviation Probability Analysis in Microperimetry.

PURPOSE: The "traffic light" color designation of differential light sensitivity used in a number of microperimeters does not encompass the conventional Total and Pattern Deviation probability analyses adopted by standard automated perimetry. We determined whether the color designation is indicative of abnormality as represented by the "gold standard" Pattern Deviation probability analysis. METHODS: Total and Pattern Deviation probability levels, using two different methods, were derived at each of 40 stimulus locations, within 7° eccentricity, from 66 ocular healthy individuals (66 eyes) who had undergone microperimetry with the Macular Integrity Assessment microperimeter. The probability levels were applied to the corresponding fields from each of 45 individuals (45 eyes) with age-related macular degeneration (AMD) and evaluated in relation to the color designation. RESULTS: Sensitivities designated in orange encompassed the entire range of Pattern Deviation probability levels (from normal to P ≤ 1%). Those designated in green were mostly normal; those in red/black generally corresponded to the ≤1% probability level. CONCLUSIONS: The green and the red/black designations are generally indicative of normal and abnormal probability values, respectively. The orange designation encompassed all probability outcomes and should not be relied upon for visual field interpretation. The evidence base indicates replacement of the color designation of sensitivity in AMD by Total Deviation and Pattern Deviation analyses. TRANSLATIONAL RELEVANCE: The use of Total and Pattern Deviation probability analyses is not universal in all microperimeters, and the derivation of these values indicates that color coding will lead to errors in evaluating visual field loss.

Low-Level Nighttime Light Therapy for Age-Related Macular Degeneration: A Randomized Clinical Trial.

Purpose: To investigate the safety, acceptability, and effectiveness of light therapy on the progression of AMD over 12 months. Methods: This was a phase I/IIa, prospective, proof-of-concept, single-center, unmasked randomized controlled trial. Sixty participants (55 to 88 years) with early AMD in the study eye and neovascular AMD (nAMD) in the fellow eye were recruited from a hospital nAMD clinic. Eligible participants were randomized (ratio 1:1) to receive light therapy or to an untreated control group. Light therapy was delivered via a light-emitting mask (peak 505 nm, 23 scotopic Td), which was worn each night for 12 months. Co-primary outcome measures were disease progression (onset of nAMD or increased drusen volume beyond test-retest limits) and change in time constant of cone dark adaptation. Other main outcomes included adverse events, compliance, and subjective sleep quality data. Results: Disease progression over 12 months was seen in 38.1% (18.1%-61.6% confidence interval [CI]) of intervention participants and 48.3% (29.4%-67.5% CI) of controls (Mantel-Haenszel test, common odds ratio = 0.763, P = 0.495). A significantly larger delay in cone adaptation was observed in the intervention group (1.66 ± 0.61 minutes) than in the control group (0.66 ± 0.49 minutes) over the follow-up period. No reported adverse events were deemed to be associated with the intervention. Conclusions: Although acceptable to the patients, light therapy did not have a substantial effect on the progression of early AMD over 12 months. Further investigation is necessary to discover the permanency and cause of the adverse effect of light therapy on dark adaptation.

The use of microperimetry in assessing visual function in age-related macular degeneration.

Microperimetry is a novel technique for assessing visual function that appears particularly suitable for age-related macular degeneration (AMD). Compared with standard automated perimetry, microperimetry offers several unique features. It simultaneously images the fundus, incorporates an eye-tracking system to correct the stimulus location for fixation loss, and identifies any preferred retinal loci. We identified 52 articles that met the inclusion criteria for a systematic review of microperimetry in the assessment of visual function in AMD. We discuss microperimetry and AMD in relation to disease severity, structural imaging outcomes, other measures of visual function, and evaluation of the efficacy of surgical and/or medical therapies in clinical trials. The evidence for the use of microperimetry in the functional assessment of AMD is encouraging. Disruptions of the ellipsoid zone band and retinal pigment epithelium are clearly associated with reduced differential light sensitivity despite the maintenance of good visual acuity. Reduced differential light sensitivity is also associated with outer segment thinning and retinal pigment epithelium thickening in early AMD and with both a thickening and a thinning of the whole retina in choroidal neovascularization. Microperimetry, however, lacks the robust diffuse and focal loss age-corrected probability analyses associated with standard automated perimetry, and the technique is currently limited by this omission.

The Effect of Gaze Angle on Visual Acuity in Infantile Nystagmus.

Purpose: Most individuals with infantile nystagmus (IN) have an idiosyncratic gaze angle at which their nystagmus intensity is minimized. Some adopt an abnormal head posture to use this "null zone," and it has therefore long been assumed that this provides people with nystagmus with improved visual acuity (VA). However, recent studies suggest that improving the nystagmus waveform could have little, if any, influence on VA; that is, VA is fundamentally limited in IN. Here, we examined the impact of the null zone on VA. Methods: Visual acuity was measured in eight adults with IN using a psychophysical staircase procedure with reversals at three horizontal gaze angles, including the null zone. Results: As expected, changes in gaze angle affected nystagmus amplitude, frequency, foveation duration, and variability of intercycle foveation position. Across participants, each parameter (except frequency) was significantly correlated with VA. Within any given individual, there was a small but significant improvement in VA (0.08 logMAR) at the null zone as compared with the other gaze angles tested. Despite this, no change in any of the nystagmus waveform parameters was significantly associated with changes in VA within individuals. Conclusions: A strong relationship between VA and nystagmus characteristics exists between individuals with IN. Although significant, the improvement in VA observed within individuals at the null zone is much smaller than might be expected from the occasionally large variations in intensity and foveation dynamics (and anecdotal patient reports of improved vision), suggesting that improvement of other aspects of visual performance may also encourage use of the null zone.

Effect of a Home Visit-Based Low Vision Rehabilitation Intervention on Visual Function Outcomes: An Exploratory Randomized Controlled Trial.

Purpose: To examine the effect of a home visit-based visual rehabilitation intervention on: (1) self-reported visual function and (2) depression, wellbeing, loneliness, adjustment to visual loss, and generic health-related quality of life. Methods: In an exploratory, assessor-masked, individually randomized, single-center controlled trial, 67 participants (age: 75.22 ± 16.21 years) with low vision were allocated either to receive the home visit-based visual rehabilitation intervention (n = 35) or to a waiting list control arm (n = 32). Outcome measures were collected by telephone interview at baseline and 6 months later. The primary outcome measure was the 48-item Veterans Affairs Low Vision Visual Functioning Questionnaire (VA LV VFQ-48). Secondary outcome measures were: the Patient Health Questionnaire; the Warwick-Edinburgh Mental Well-being Scale, the Adjustment to Age-related Visual Loss Scale, the standardized health-related quality of life questionnaire, and the University of California, Los Angeles Loneliness Scale. Questionnaire scores at follow-up were analyzed using analysis of covariance, controlling for the baseline score and the variables, age, number of comorbidities, visual acuity, and baseline wellbeing score. Results: Visual function (VA LV VFQ-48) improved at follow-up in both groups, with a significantly greater improvement demonstrated by the intervention group (95% confidence interval, 0.33-0.68 logits, P = 0.031), with a moderate effect size (0.55). Secondary outcomes did not indicate any statistically significant differences between groups. Conclusions: The study provides preliminary evidence that a home visit-based visual rehabilitation intervention has a positive influence on vision-related functional outcomes. A larger trial with an expanded intervention to include a mental health component and cost-effectiveness analysis is needed. (ISRCTN.com number, 44807874.).

Automated Retinal Layer Segmentation Using Spectral Domain Optical Coherence Tomography: Evaluation of Inter-Session Repeatability and Agreement between Devices.

Retinal and intra-retinal layer thicknesses are routinely generated from optical coherence tomography (OCT) images, but on-board software capabilities and image scaling assumptions are not consistent across devices. This study evaluates the device-independent Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) for automated intra-retinal layer segmentation and image scaling for three OCT systems. Healthy participants (n = 25) underwent macular volume scans using a Cirrus HD-OCT (Zeiss), 3D-OCT 1000 (Topcon), and a non-commercial long-wavelength (1040nm) OCT on two occasions. Mean thickness of 10 intra-retinal layers was measured in three ETDRS subfields (fovea, inner ring and outer ring) using the Iowa Reference Algorithms. Where available, total retinal thicknesses were measured using on-board software. Measured axial eye length (AEL)-dependent scaling was used throughout, with a comparison made to the system-specific fixed-AEL scaling. Inter-session repeatability and agreement between OCT systems and segmentation methods was assessed. Inter-session coefficient of repeatability (CoR) for the foveal subfield total retinal thickness was 3.43µm, 4.76µm, and 5.98µm for the Zeiss, Topcon, and long-wavelength images respectively. For the commercial software, CoR was 4.63µm (Zeiss) and 7.63µm (Topcon). The Iowa Reference Algorithms demonstrated higher repeatability than the on-board software and, in addition, reliably segmented all 10 intra-retinal layers. With fixed-AEL scaling, the algorithm produced significantly different thickness values for the three OCT devices (P<0.05), with these discrepancies generally characterized by an overall offset (bias) and correlations with axial eye length for the foveal subfield and outer ring (P<0.05). This correlation was reduced to an insignificant level in all cases when AEL-dependent scaling was used. Overall, the Iowa Reference Algorithms are viable for clinical and research use in healthy eyes imaged with these devices, however ocular biometry is required for accurate quantification of OCT images.

Psychosocial interventions to improve mental health in adults with vision impairment: systematic review and meta-analysis.

PURPOSE: To systematically assess the literature on psychosocial interventions to improve mental health (i.e. depression, anxiety, mental fatigue, loneliness, psychological stress and psychological well-being) in visually impaired adults (≥18 years). METHODS: The databases Medline, Embase and Psychinfo were searched for relevant studies, which were categorised into randomised controlled trials (RCTs), non-RCTs and before and after comparisons (BA). The Cochrane Collaboration Risk of Bias Tool was used to assess study quality. Standardised mean differences (SMD) were calculated to quantitatively summarise the outcomes of the RCTs and non-RCTs in a meta-analysis. Meta-regression was used to explore sources of heterogeneity in the data. RESULTS: The search identified 27 papers (published between 1981 and 2015), describing the outcomes of 22 different studies (14 RCTs, four non-RCTs, and four BAs). Pooled analyses showed that interventions significantly reduced depressive symptoms (SMD -0.30, 95% confidence interval (CI) -0.60 to -0.01), while effects on anxiety symptoms, mental fatigue, psychological stress and psychological well-being were non-significant. Meta-regression analyses showed homogeneity in effect sizes across a range of intervention, population, and study characteristics. Only a higher age of participants was associated with less effective results on depressive symptoms (b = 0.03, 95% CI 0.01 to 0.05), psychological stress (b = 0.07, 95% CI 0.01 to 0.13) and psychological well-being (b = -0.03, 95% CI -0.05 to 0.01). However, after removing a clear outlier the overall effect on depressive symptoms and the influence of age on depressive symptoms and psychological stress were no longer significant, while the influence of age on psychological well-being remained. CONCLUSIONS: There is currently only limited evidence for the effectiveness of psychosocial interventions in the field of low vision. More well-designed trials are needed with specific attention for interventions tailored to the needs of elderly patients.

Depression in Visual Impairment Trial (DEPVIT): A Randomized Clinical Trial of Depression Treatments in People With Low Vision.

PURPOSE: The purpose of this study was to compare two interventions for depression, problem solving treatment (PST) and referral to the patient's physician, with a waiting-list control group in people with sight loss and depressive symptoms. METHODS: This was an assessor-masked, exploratory, multicenter, randomized clinical trial, with concurrent economic analysis. Of 1008 consecutive attendees at 14 low-vision rehabilitation centers in Britain, 43% (n = 430) screened positive for depressive symptoms on the Geriatric Depression Scale and 85 of these attendees participated in the trial. Eligible participants were randomized in the ratio 1:1:1 to PST, referral to their physician, or a waiting-list control arm. PST is a manualized talking intervention delivered by a trained therapist who teaches people over six to eight sessions to implement a seven-step method for solving their problems. Referral to the physician involved sending a referral letter to the person's physician, encouraging him or her to consider treatment according to the stepped care protocol recommended by the U.K.'s National Institute of Health and Care Excellence. The primary outcome was change in depressive symptoms (6 months after baseline) as determined by the Beck Depression Inventory. RESULTS: At 6 months, Beck Depression Inventory scores reduced by 1.05 (SD 8.85), 2.11 (SD 7.60), and 2.68 (SD 7.93) in the waiting-list control, referral, and PST arms, respectively. The cost per patient of the PST intervention was £1176 in Wales and £1296 in London. CONCLUSIONS: Depressive symptoms improved most in the PST group and least in the control group. However, the change was small and the uncertainty of the measurements relatively large.

Effect of rehabilitation worker input on visual function outcomes in individuals with low vision: study protocol for a randomised controlled trial.

BACKGROUND: Visual Rehabilitation Officers help people with a visual impairment maintain their independence. This intervention adopts a flexible, goal-centred approach, which may include training in mobility, use of optical and non-optical aids, and performance of activities of daily living. Although Visual Rehabilitation Officers are an integral part of the low vision service in the United Kingdom, evidence that they are effective is lacking. The purpose of this exploratory trial is to estimate the impact of a Visual Rehabilitation Officer on self-reported visual function, psychosocial and quality-of-life outcomes in individuals with low vision. METHODS/DESIGN: In this exploratory, assessor-masked, parallel group, randomised controlled trial, participants will be allocated either to receive home visits from a Visual Rehabilitation Officer (n = 30) or to a waiting list control group (n = 30) in a 1:1 ratio. Adult volunteers with a visual impairment, who have been identified as needing rehabilitation officer input by a social worker, will take part. Those with an urgent need for a Visual Rehabilitation Officer or who have a cognitive impairment will be excluded. The primary outcome measure will be self-reported visual function (48-item Veterans Affairs Low Vision Visual Functioning Questionnaire). Secondary outcome measures will include psychological and quality-of-life metrics: the Patient Health Questionnaire (PHQ-9), the Warwick-Edinburgh Mental Well-being Scale (WEMWBS), the Adjustment to Age-related Visual Loss Scale (AVL-12), the Standardised Health-related Quality of Life Questionnaire (EQ-5D) and the UCLA Loneliness Scale. The interviewer collecting the outcomes will be masked to the group allocations. The analysis will be undertaken on a complete case and intention-to-treat basis. Analysis of covariance (ANCOVA) will be applied to follow-up questionnaire scores, with the baseline score as a covariate. DISCUSSION: This trial is expected to provide robust effect size estimates of the intervention effect. The data will be used to design a large-scale randomised controlled trial to evaluate fully the Visual Rehabilitation Officer intervention. A rigorous evaluation of Rehabilitation Officer input is vital to direct a future low vision rehabilitation strategy and to help direct government resources. TRIAL REGISTRATION: The trial was registered with ( ISRCTN44807874 ) on 9 March 2015.

Electrophysiological ON and OFF Responses in Autosomal Dominant Optic Atrophy.

PURPOSE: To assess the effect of autosomal dominant optic atrophy (ADOA) on ON and OFF retinal ganglion cell (RGC) function by evaluating the ON and OFF components of the photopic negative response (PhNR). METHODS: Twelve participants from six families with OPA1 ADOA and 16 age-matched controls were recruited. Electrophysiological assessment involved pattern ERGs (PERGs), focal (20°) and full-field long-duration (250 ms) flash ERGs using a red light-emitting diode flash on a rod-saturating blue background, and full-field brief (300 µs) xenon flash ERGs using a red filter over a continuous rod saturating blue background. Amplitudes and implicit times of the ERG components were analyzed and the diagnostic potential of each electrophysiological technique was determined by generating receiver operating characteristic (ROC) curves. RESULTS: Mean amplitudes of the N95 and all PhNRs, except the full-field PhNRON, were significantly reduced in participants with ADOA (P < 0.01). Subtraction of the group-averaged focal ERG of ADOA participants from that of controls showed an equal loss in the focal PhNRON and PhNROFF components, whereas in the full-field ERG the loss in the PhNROFF was greater than that in the PhNRON component. The areas under the ROC curve (AUC) for the focal PhNRON (0.92), focal PhNROFF (0.95), and full-field PhNROFF (0.83), were not significantly different from that of the PERG N95 (0.99). CONCLUSIONS: In patients with ADOA, the PhNRON and PhNROFF components are nearly symmetrically reduced in the long-duration ERG, suggesting that ON- and OFF-RGC pathways may be equally affected.

Stepped care for depression and anxiety in visually impaired older adults: multicentre randomised controlled trial.

STUDY QUESTION: Is stepped care compared with usual care effective in preventing the onset of major depressive, dysthymic, and anxiety disorders in older people with visual impairment (caused mainly by age related eye disease) and subthreshold depression and/or anxiety? METHODS: 265 people aged ≥50 were randomly assigned to a stepped care programme plus usual care (n=131) or usual care only (n=134). Supervised occupational therapists, social workers, and psychologists from low vision rehabilitation organisations delivered the stepped care programme, which comprised watchful waiting, guided self help based on cognitive behavioural therapy, problem solving treatment, and referral to a general practitioner. The primary outcome was the 24 month cumulative incidence (seven measurements) of major depressive dysthymic and/or anxiety disorders (panic disorder, agoraphobia, social phobia, and generalised anxiety disorder). Secondary outcomes were change in symptoms of depression and anxiety, vision related quality of life, health related quality of life, and adaptation to vision loss over time up to 24 months' follow-up. STUDY ANSWER AND LIMITATIONS: 62 participants (46%) in the usual care group and 38 participants (29%) from the stepped care group developed a disorder. The intervention was associated with a significantly reduced incidence (relative risk 0.63, 95% confidence interval 0.45 to 0.87; P=0.01), even if time to the event was taken into account (adjusted hazard ratio 0.57, 0.35 to 0.93; P=0.02). The number needed to treat was 5.8 (3.5 to 17.3). The dropout rate was fairly high (34.3%), but rates were not significantly different for the two groups, indicating that the intervention was as acceptable as usual care. Participants who volunteered and were selected for this study might not be representative of visually impaired older adults in general (responders were significantly younger than non-responders), thereby reducing the generalisability of the outcomes. WHAT THIS STUDY ADDS: Stepped care seems to be a promising way to deal with depression and anxiety in visually impaired older adults. This approach could lead to standardised strategies for the screening, monitoring, treatment, and referral of visually impaired older adults with depression and anxiety. FUNDING, COMPETING INTERESTS, DATA SHARING: Funded by ZonMw InZicht, the Dutch Organisation for Health Research and Development-InSight Society. There are no competing interests. Full dataset and statistical code are available from the corresponding author.Study registration www.trialregister.nl NTR3296.