KRAS4A directly regulates hexokinase 1.

The most frequently mutated oncogene in cancer is KRAS, which uses alternative fourth exons to generate two gene products (KRAS4A and KRAS4B) that differ only in their C-terminal membrane-targeting region1. Because oncogenic mutations occur in exons 2 or 3, two constitutively active KRAS proteins-each capable of transforming cells-are encoded when KRAS is activated by mutation2. No functional distinctions among the splice variants have so far been established. Oncogenic KRAS alters the metabolism of tumour cells3 in several ways, including increased glucose uptake and glycolysis even in the presence of abundant oxygen4 (the Warburg effect). Whereas these metabolic effects of oncogenic KRAS have been explained by transcriptional upregulation of glucose transporters and glycolytic enzymes3-5, it is not known whether there is direct regulation of metabolic enzymes. Here we report a direct, GTP-dependent interaction between KRAS4A and hexokinase 1 (HK1) that alters the activity of the kinase, and thereby establish that HK1 is an effector of KRAS4A. This interaction is unique to KRAS4A because the palmitoylation-depalmitoylation cycle of this RAS isoform enables colocalization with HK1 on the outer mitochondrial membrane. The expression of KRAS4A in cancer may drive unique metabolic vulnerabilities that can be exploited therapeutically.

FKBP12 binds to acylated H-ras and promotes depalmitoylation.

A cycle of palmitoylation/depalmitoylation of H-Ras mediates bidirectional trafficking between the Golgi apparatus and the plasma membrane, but nothing is known about how this cycle is regulated. We show that the prolyl isomerase (PI) FKBP12 binds to H-Ras in a palmitoylation-dependent fashion and promotes depalmitoylation. A variety of inhibitors of the PI activity of FKBP12, including FK506, rapamycin, and cycloheximide, increase steady-state palmitoylation. FK506 inhibits retrograde trafficking of H-Ras from the plasma membrane to the Golgi in a proline 179-dependent fashion, augments early GTP loading of Ras in response to growth factors, and promotes H-Ras-dependent neurite outgrowth from PC12 cells. These data demonstrate that FKBP12 regulates H-Ras trafficking by promoting depalmitoylation through cis-trans isomerization of a peptidyl-prolyl bond in proximity to the palmitoylated cysteines.

K-Ras4A splice variant is widely expressed in cancer and uses a hybrid membrane-targeting motif.

The two products of the KRAS locus, K-Ras4A and K-Ras4B, are encoded by alternative fourth exons and therefore, possess distinct membrane-targeting sequences. The common activating mutations occur in exons 1 or 2 and therefore, render both splice variants oncogenic. K-Ras4A has been understudied, because it has been considered a minor splice variant. By priming off of the splice junction, we developed a quantitative RT-PCR assay for K-Ras4A and K-Ras4B message capable of measuring absolute amounts of the two transcripts. We found that K-Ras4A was widely expressed in 30 of 30 human cancer cell lines and amounts equal to K-Ras4B in 17 human colorectal tumors. Using splice variant-specific antibodies, we detected K-Ras4A protein in several tumor cell lines at a level equal to or greater than that of K-Ras4B. In addition to the CAAX motif, the C terminus of K-Ras4A contains a site of palmitoylation as well as a bipartite polybasic region. Although both were required for maximal efficiency, each of these could independently deliver K-Ras4A to the plasma membrane. Thus, among four Ras proteins, K-Ras4A is unique in possessing a dual membrane-targeting motif. We also found that, unlike K-Ras4B, K-Ras4A does not bind to the cytosolic chaperone δ-subunit of cGMP phosphodiesterase type 6 (PDE6δ). We conclude that efforts to develop anti-K-Ras drugs that interfere with membrane trafficking will have to take into account the distinct modes of targeting of the two K-Ras splice variants.

A national survey of the use of pachymeters by optometrists in Scotland: experience, views and barriers to use.

PURPOSE: Thin central corneal thickness (CCT) is a risk factor for glaucoma. In 2016 all optometry practices in Scotland were provided with pachymeters aiming to improve risk assessment and accuracy of referrals to secondary care. We examined optometrists' experience and views of pachymetry, including perceived barriers to pachymetry in primary care. METHODS: A questionnaire was sent using the REDCap electronic data capture tool to all 1264 optometrists registered with NHS Education for Scotland (NES). The questionnaire evaluated year of qualification, previous pachymetry training, confidence performing and interpreting pachymetry, and perceived indications for and barriers to use. RESULTS: Respondents numbered 418 out of 1264 (33%) optometrists, of whom 56% had previous training in pachymetry. Those that had previous training were significantly more likely to report pachymetry to be useful, with median (inter-quartile range) usefulness score of 86 (71-98) where 0 indicated not at all useful, and 100 extremely useful, vs 76 (58-90), Wilcoxon-Mann-Whitney test, z = -4.67, p < 0.01. There are no valid scales for adjusting intraocular pressure (IOP) using CCT, however 45% of respondents reported using a scale. Optometrists planned to use pachymetry when assessing patients with ocular hypertension or suspected glaucoma. The greatest perceived barrier was the process of decontaminating or cleaning the pachymeter between patients, followed by lack of time and lack of training. CONCLUSIONS: Although the majority of optometrists were interested in performing pachymetry, many lacked confidence in performing and interpreting the results. Forty-one percent of those who reported training in pachymetry still used non-validated scales to convert IOP measurements illustrating the need for further training.

Phosphorylated K-Ras limits cell survival by blocking Bcl-xL sensitization of inositol trisphosphate receptors.

K-Ras4B is targeted to the plasma membrane by a farnesyl modification that operates in conjunction with a polybasic domain. We characterized a farnesyl-electrostatic switch whereby protein kinase C phosphorylates K-Ras4B on serine 181 in the polybasic region and thereby induces translocation from the plasma membrane to internal membranes that include the endoplasmic reticulum (ER) and outer mitochondrial membrane. This translocation is associated with cell death. Here we have explored the mechanism of phospho-K-Ras4B toxicity and found that GTP-bound, phosphorylated K-Ras4B associates with inositol trisphosphate receptors on the ER in a Bcl-xL-dependent fashion and, in so doing, blocks the ability of Bcl-xL to potentiate the InsP3 regulated flux of calcium from ER to mitochondria that is required for efficient respiration, inhibition of autophagy, and cell survival. Thus, we have identified inositol trisphosphate receptors as unique effectors of K-Ras4B that antagonize the prosurvival signals of other K-Ras effectors.

Visual impairment is associated with physical and mental comorbidities in older adults: a cross-sectional study.

BACKGROUND: Visual impairment is common in older people and the presence of additional health conditions can compromise health and rehabilitation outcomes. A small number of studies have suggested that comorbities are common in visual impairment; however, those studies have relied on self-report and have assessed a relatively limited number of comorbid conditions. METHODS: We conducted a cross-sectional analysis of a dataset of 291,169 registered patients (65-years-old and over) within 314 primary care practices in Scotland, UK. Visual impairment was identified using Read Code ever recorded for blindness and/or low vision (within electronic medical records). Prevalence, odds ratios (from prevalence rates standardised by stratifying individuals by age groups (65 to 69 years; 70 to 74; 75 to 79; 80 to 84; and 85 and over), gender and deprivation quintiles) and 95% confidence intervals (95% CI) of 37 individual chronic physical/mental health conditions and total number of conditions were calculated and compared for those with visual impairment to those without. RESULTS: Twenty seven of the 29 physical health conditions and all eight mental health conditions were significantly more likely to be recorded for individuals with visual impairment compared to individuals without visual impairment, after standardising for age, gender and social deprivation. Individuals with visual impairment were also significantly more likely to have more comorbidities (for example, five or more conditions (odds ratio (OR) 2.05 95% CI 1.94 to 2.18)). CONCLUSIONS: Patients aged 65 years and older with visual impairment have a broad range of physical and mental health comorbidities compared to those of the same age without visual impairment, and are more likely to have multiple comorbidities. This has important implications for clinical practice and for the future design of integrated services to meet the complex needs of patients with visual impairment, for example, embedding depression and hearing screening within eye care services.

NRAS is unique among RAS proteins in requiring ICMT for trafficking to the plasma membrane.

Isoprenylcysteine carboxyl methyltransferase (ICMT) is the third of three enzymes that sequentially modify the C-terminus of CaaX proteins, including RAS. Although all four RAS proteins are substrates for ICMT, each traffics to membranes differently by virtue of their hypervariable regions that are differentially palmitoylated. We found that among RAS proteins, NRAS was unique in requiring ICMT for delivery to the PM, a consequence of having only a single palmitoylation site as its secondary affinity module. Although not absolutely required for palmitoylation, acylation was diminished in the absence of ICMT. Photoactivation and FRAP of GFP-NRAS revealed increase flux at the Golgi, independent of palmitoylation, in the absence of ICMT. Association of NRAS with the prenyl-protein chaperone PDE6δ also required ICMT and promoted anterograde trafficking from the Golgi. We conclude that carboxyl methylation of NRAS is required for efficient palmitoylation, PDE6δ binding, and homeostatic flux through the Golgi, processes that direct delivery to the plasma membrane.

Measuring patient anxiety in primary care: Rasch analysis of the 6-item Spielberger State Anxiety Scale.

OBJECTIVES: The 6-item Spielberger State Anxiety Scale has been used as a replacement of the original version in many health-care studies. The purpose of this study was to evaluate the measurement properties of the shortened 6-item Spielberger State Anxiety Scale using Rasch analysis in general medical practice patients (N=297). METHODS: Participants (aged 16 years or above) were recruited on a consecutive basis from three general medical practices. Prior to their appointment, participants were asked to complete a 6-item Spielberger State Anxiety Scale. RESULTS: The results of the study showed that the scale is unidimentional, and each item measures a different level of patient anxiety. The rating scale operated well and item and person reliability was good. Furthermore, principal-components analysis of the residuals confirmed the scale measures a unitary concept. A scoring key was generated to allow conversion of raw scores to a continuous measurement. CONCLUSION: The 6-item Spielberger State Anxiety Scale is shorter than the original version and has good psychometric properties. This would suggest the scale is a valid alternative to the full version for use in primary health-care practice and research.

The newly established primary care based Welsh Low Vision Service is effective and has improved access to low vision services in Wales.

AIM: The aim of this study was to determine whether the new, primary care based, Welsh Low Vision Service (WLVS) improved access to low vision services in Wales and was effective. METHOD: The impact of the WLVS was determined by measuring the number of low vision appointments; travel time to the nearest service provider; and waiting times for low vision services for 1 year before, and for 1 year after, its establishment. Change in self-report visual function (using the 7 item NEI-VFQ), near visual acuity, patient satisfaction and use of low vision aids were used to determine the effectiveness of the service. RESULTS: Following instigation of the WLVS, the number of low vision assessments increased by 51.7%, the waiting time decreased from more than 6 months to less than 2 months for the majority of people, and journey time to the nearest service provider reduced for 80% of people. Visual disability scores improved significantly (p < 0.001) by 0.79 logits and 97.42% patients found the service helpful. CONCLUSIONS: The extension of low vision rehabilitation services into primary care identified a considerable unmet burden of need as evidenced by the substantial increase in the number of low vision assessments provided in Wales. The new service is effective and exhibits improved access.

Regulation of Cdc42 GTPase activity in the formation of hyphae in Candida albicans.

The human fungal pathogen Candida albicans can switch between yeast, pseudohyphal, and hyphal morphologies. To investigate whether the distinctive characteristics of hyphae are due to increased activity of the Cdc42 GTPase, strains lacking negative regulators of Cdc42 were constructed. Unexpectedly, the deletion of the Cdc42 Rho guanine dissociation inhibitor RDI1 resulted in reduced rather than enhanced polarized growth. However, when cells lacking both Cdc42 GTPase-activating proteins, encoded by RGA2 and BEM3, were grown under pseudohyphal-promoting conditions the bud was highly elongated and lacked a constriction at its base, so that its shape resembled a hyphal germ tube. Moreover, a Spitzenkörper was present at the bud tip, a band of disorganized septin was present at bud base, true septin rings formed within the bud, and nuclei migrated out of the mother cell before the first mitosis. These are all characteristic features of a hyphal germ tube. Intriguingly, we observed hyphal-specific phosphorylation of Rga2, suggesting a possible mechanism for Cdc42 activation during normal hyphal development. In contrast, expression of Cdc42(G12V), which is constitutively GTP bound because it lacks GTPase activity, resulted in swollen cells with prominent and stable septin bars. These results suggest the development of hyphal-specific characteristics is promoted by Cdc42-GTP in a process that also requires the intrinsic GTPase activity of Cdc42.

Evaluating the association between anxiety and satisfaction.

PURPOSE: Low patient satisfaction is problematic within optometric practice. However, to date, it is not known how patient anxiety affects this patient variable. Therefore, the purpose of this study was to determine whether patients who report higher levels of preexamination anxiety have lower levels of satisfaction postconsultation. METHODS: Optometric patient anxiety and patient satisfaction were measured using self-report questionnaires. A total of 197 participants (82 males, 115 females; mean age 57.1 +/- 18.6) completed the Optometric Patient Anxiety Scale before their eye examination. The Rapport subscale (extracted from the Medical Interview Satisfaction Scale) was completed after the eye examination. RESULTS: Validity of the Optometric Patient Anxiety Scale and Rapport subscale for this population was confirmed with Rasch analysis and item estimates calculated. Linear regression identified a significant relationship between optometric anxiety and satisfaction (p < 0.01). CONCLUSIONS: This is the first time that a relationship between preconsultation patient anxiety and postconsultation satisfaction has been documented within optometric practice. This indicates that if patient optometric anxiety can be reduced, there may be an improvement in patient satisfaction.

Predicting state anxiety in optometric practice.

PURPOSE: Patient anxiety has been shown to be detrimental to healthcare consultations and their outcomes. To date, little is known about the causes of patient anxiety in optometric practice. Therefore, the purpose of this study was to identify the predictors of state anxiety for patients attending optometric consultations. METHODS: Three hundred sixty six participants (127 male, 239 female; mean age, 54.5; SD +/- 18.0) took part in the study. Each participant completed a preconsultation questionnaire including established measures of "state" anxiety, "trait" anxiety, study specific outcome expectancies, and biographical data. Multiple linear regression analysis was used to identify which variables predict state anxiety. RESULTS: Multiple linear regression analysis showed that the heightened trait anxiety, expecting "bad news" and being a non-spectacle wearer are independent predictors of increased state anxiety. R was 0.33, i.e., the regression model explained 33% of the variance. CONCLUSIONS: This is the first time that the predictors of state anxiety in optometric practice have been identified. Optometrists should recognize that patients who are "anxious types," who may be expecting "bad news" and who do not wear spectacles may be more anxious.

Regulation of NOTCH signaling by RAB7 and RAB8 requires carboxyl methylation by ICMT.

Isoprenylcysteine carboxyl methyltransferase (ICMT) methylesterifies C-terminal prenylcysteine residues of CaaX proteins and some RAB GTPases. Deficiency of either ICMT or NOTCH1 accelerates pancreatic neoplasia in Pdx1-Cre;LSL-KrasG12D mice, suggesting that ICMT is required for NOTCH signaling. We used Drosophila melanogaster wing vein and scutellar bristle development to screen Rab proteins predicted to be substrates for ICMT (ste14 in flies). We identified Rab7 and Rab8 as ICMT substrates that when silenced phenocopy ste14 deficiency. ICMT, RAB7, and RAB8 were all required for efficient NOTCH1 signaling in mammalian cells. Overexpression of RAB8 rescued NOTCH activation after ICMT knockdown both in U2OS cells expressing NOTCH1 and in fly wing vein development. ICMT deficiency induced mislocalization of GFP-RAB7 and GFP-RAB8 from endomembrane to cytosol, enhanced binding to RABGDI, and decreased GTP loading of RAB7 and RAB8. Deficiency of ICMT, RAB7, or RAB8 led to mislocalization and diminished processing of NOTCH1-GFP. Thus, NOTCH signaling requires ICMT in part because it requires methylated RAB7 and RAB8.

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.

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.).

Apoptosis and mutation in the murine small intestine: loss of Mlh1- and Pms2-dependent apoptosis leads to increased mutation in vivo.

The mismatch repair (MMR) protein Msh2 has been shown to function in the apoptotic response to alkylating agents in vivo. Here, we extend these studies to the MutL homologues (MLH) Mlh1 and Pms2 by analysing the apoptotic response within the small intestine of gene targeted strains. We demonstrate significant differences between Msh2, Mlh1 and Pms2 mutations in influencing apoptotic signalling following 50mg/kg N-methyl-nitrosourea (NMNU), with no obvious reliance upon either Mlh1 or Pms2. However, following exposure to 100mg/kg temozolomide or lower levels of NMNU (10mg/kg) both Mlh1- and Pms2-dependent apoptosis was observed, indicating that the apoptotic response at these levels of DNA damage is dependent on the MutL homologues. Given our ability to observe a MutLalpha dependence of the apoptotic response, we tested whether perturbations of this response directly translate into increases in mutation frequency in vivo. We show that treatment with temozolomide or 10mg/kg NMNU significantly increases mutation in both the Mlh1 and Pms2 mutant mice. At higher levels of NMNU, where the apoptotic response is independent of Mlh1 and Pms2, no gene dependent increase in mutation frequency was observed. These results argue that the MutSalpha and MutLalpha are not equally important in their ability to signal apoptosis. However, when MMR does mediate apoptosis, perturbation of this response leads to long-term persistence of mutant cells in vivo.

Improving the psychometric utility of the hypomania checklist (HCL-32): a Rasch analysis approach.

BACKGROUND: The HCL-32 is a widely-used screening questionnaire for hypomania. We aimed to use a Rasch analysis approach to (i) evaluate the measurement properties, principally unidimensionality, of the HCL-32, and (ii) generate a score table to allow researchers to convert raw HCL-32 scores into an interval-level measurement which will be more appropriate for statistical analyses. METHODS: Subjects were part of the Bipolar Disorder Research Network (BDRN) study with DSM-IV bipolar disorder (n=389). Multidimensionality was assessed using the Rasch fit statistics and principle components analysis of the residuals (PCA). Item invariance (differential item functioning, DIF) was tested for gender, bipolar diagnosis and current mental state. Item estimates and reliabilities were calculated. RESULTS: Three items (29, 30, 32) had unacceptable fit to the Rasch unidimensional model. Item 14 displayed significant DIF for gender and items 8 and 17 for current mental state. Item estimates confirmed that not all items measure hypomania equally. LIMITATIONS: This sample was recruited as part of a large ongoing genetic epidemiology study of bipolar disorder and may not be fully representative of the broader clinical population of individuals with bipolar disorder. CONCLUSION: The HCL-32 is unidimensional in practice, but measurements may be further strengthened by the removal of four items. Re-scored linear measurements may be more appropriate for clinical research.

Depression and multimorbidity: a cross-sectional study of 1,751,841 patients in primary care.

BACKGROUND: Depression is common in many chronic physical health disorders, but the nature and extent of physical health comorbidities in depression, particularly within large population-based samples of patients, and how these comorbidities relate to factors such as age, sex, and social deprivation, are unknown. We aimed to assess the nature and extent of multiple physical health comorbidities in primary care patients with depression within a large and representative Scottish dataset. METHOD: This study was a cross-sectional secondary data analysis of 314 primary care practices in Scotland (from the Primary Care Clinical Informatics Unit at the University of Aberdeen, Scotland, March 31, 2007), including 143,943 people with depression and 1,280,435 controls. The outcomes assessed were 32 common chronic physical health conditions, adjusted for age, sex, and social deprivation. Depression was defined as a Read code for depression recorded within last year and/or 4 or more antidepressant prescriptions (excluding low-dose tricyclic antidepressants) within the last year. RESULTS: Individuals in primary care with depression were more likely than individuals without depression to have every one of the 32 comorbid physical conditions we assessed, even after adjusting for age, sex, and deprivation. The depression group was also significantly more likely to have multiple levels of comorbidity, including 2 physical health conditions (OR = 1.55; 95% CI, 1.53-1.58), 3 physical health conditions (OR = 1.84; 95% CI, 1.81-1.87), 4 physical health conditions (OR = 2.06; 95% CI, 2.01-2.11; P < .001), and 5 or more physical health conditions (OR = 2.65; 95% CI, 2.59-2.71; P < .001). CONCLUSION: Depression in primary care is associated with a very wide range of physical health comorbidities and considerable medical burden. The nature and extent of this multimorbidity and the important association with social deprivation have not been previously described within a large and representative dataset of routine primary care data. Our findings have important implications for the integrated management of depression and physical health problems in the United Kingdom and throughout the world.

Effectiveness of the community-based Low Vision Service Wales: a long-term outcome study.

AIMS: To evaluate the long-term effectiveness of the community-based Low Vision Service Wales (LVSW). METHODS: A long-term observational study of the Government-funded, community-based, low-vision rehabilitation service which operates in over 180 optometry practices in Wales. Participants were recruited from the LVSW (n=342; 246 women; median age 82 years) at baseline (before the Low Vision intervention). The primary outcome measure was change in visual disability as evaluated by the seven-item National Eye Institute Visual Function Questionnaire (NEI-VFQ). Change was measured on the same cohort at three separate time points, and comparisons were made between these: baseline-3 months; 3-18 months; baseline-18 months. Secondary outcome measures included: use of low-vision aids (LVAs) and satisfaction with the service provided. RESULTS: Questionnaires were sent to 281 participants (whose visual disability had been measured at baseline and 3 months) at 18 months postintervention. Responses were received from 190 (67.6%) people; 24 were deceased. Self-reported visual disability was significantly reduced (Wilcoxon Signed Rank (WSR) test: p<0.001) between baseline and 18 months by -0.28 logits (-1.24 to 0.52). This was less than that found between baseline and 3 months; -0.61 logits (-1.81 to 0.02). At 18 months, 79% patients used their LVAs at least once a week which was not significantly different to that found at 3 months (WSR: p=0.127). CONCLUSIONS: This study provides evidence that the effect of the LVSW persists over a period of 18 months; disability is reduced from baseline, and use of LVAs remains high.