Psychological and cognitive determinants of vision function in age-related macular degeneration.

OBJECTIVE: To investigate the effect of coping strategies, depression, physical health, and cognition on National Eye Institute Visual Function Questionnaire scores obtained at baseline in a sample of older patients with age-related macular degeneration (AMD) enrolled in the Improving Function in AMD Trial, a randomized controlled clinical trial that compares the efficacy of problem-solving therapy with that of supportive therapy to improve vision function in patients with AMD. METHODS: Baseline evaluation of 241 older outpatients with advanced AMD who were enrolled in a clinical trial testing the efficacy of a behavioral intervention to improve vision function. Vision function was characterized as an interval-scaled, latent variable of visual ability based on the near-vision subscale of the National Eye Institute Vision Function Questionnaire-25 plus Supplement. RESULTS: Visual ability was highly correlated with visual acuity. However, a multivariate model revealed that patient coping strategies and cognitive function contributed to their ability to perform near-vision activities independent of visual acuity. CONCLUSIONS: Patients with AMD vary in their coping strategies and cognitive function and in their visual acuity, and that variability determines patients\u27 self-report of vision function. Understanding patient coping mechanisms and cognition may help increase the precision of vision rating scales and suggest new interventions to improve vision function and quality of life in patients with AMD. Trial Registration clinicaltrials.gov Identifier: NCT00572039

Improving function in Age-Related Macular Degeneration: design and methods of a randomized clinical trial.

Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD\u27s prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population

Personality and functional vision in older adults with age-related macular degeneration

Introduction: The purpose of the study was to determine whether personality traits influence self-reported functional vision in patients with age-related macular degeneration (AMD). Methods: This is a prospective cross-sectional analysis of baseline data from the Low Vision Depression Prevention Trial. Participants (N = 182) over age 65 with bilateral AMD, visual acuity worse than 20/70 in the better-seeing eye, and subthreshold depression were recruited from the Wills Eye Hospital retina practice. Assessments included visual acuity, contrast sensitivity, National Eye Institute Visual Function Questionnaire-25 plus Supplement (NEI VFQ-25) near and distance subscales, depression, and personality testing. Structural equation models were used to investigate the relationship of the NEI VFQ near activities and distance activities with the various demographic, clinical, and psychological predictors. Results: In the single-predictor model for near functional vision, visual acuity at logMAR ≤ 1 (estimate = -0.33 [95% confidence interval {CI} -0.46, -0.20]; p ≤ 0.001), neuroticism (estimate = -0.05 [95% CI -0.08, -0.01]; p = 0.01), and education (estimate = -0.08 [95% CI 0.01, 0.15]; p = 0.03) were statistically significant predictors. In the single-predictor model for distance functional vision, only visual acuity at logMAR ≤ 1 (estimate = -0.49 [95% CI -0.69, -0.29]; p ≤ 0.001) and neuroticism (estimate = -0.09 [95% CI -0.15, 0.02]; p = 0.008) were statistically significant predictors. Discussion: Self-reported functional vision depends on the severity of vision loss as well as the personality trait of neuroticism. Implications for practitioners: Assessment of personality traits, particularly neuroticism, may increase the precision of rating scales of functional vision and suggest new rehabilitative interventions to improve the functional vision and quality of life of patients with AMD © 2014 AFB, All Rights Reserved

Improving Function in Age-related Macular Degeneration: A Randomized Clinical Trial.

PURPOSE: To compare the efficacy of problem-solving therapy (PST) with supportive therapy (ST) to improve targeted vision function (TVF) in age-related macular degeneration (AMD). DESIGN: Single-masked, attention-controlled, randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects). PARTICIPANTS: Patients with AMD (n = 241) attending retina practices. INTERVENTIONS: Whereas PST uses a structured problem-solving approach to reduce vision-related task difficulty, ST is a standardized attention-control treatment. MAIN OUTCOME MEASURES: We assessed TVF, the 25-item National Eye Institute Vision Function Questionnaire plus Supplement (NEI VFQ), the Activities Inventory (AI), and vision-related quality of life (QoL). RESULTS: There were no between-group differences in TVF scores at 3 (P = 0.47) or 6 (P = 0.62) months. For PST subjects, mean ± standard deviation TVF scores improved from 2.71±0.52 at baseline to 2.18±0.88 at 3 months (P = 0.001) and were 2.18±0.95 at 6 months (change from 3 to 6 months, P = 0.74). For ST subjects, TVF scores improved from 2.73±0.52 at baseline to 2.14±0.96 at 3 months (P = 0.001) and were 2.15±0.96 at 6 months (change from 3 to 6 months, P = 0.85). Similar proportions of PST and ST subjects had less difficulty performing a TVF goal at 3 months (77.4% vs 78.6%, respectively; P = 0.83) and 6 months (76.2% vs 79.1%, respectively; P = 0.61). There were no changes in the NEI VFQ or AI. Vision-related QoL improved for PST relative to ST subjects at 3 months (F(4, 192) = 2.46; P = 0.05) and at 6 months (F(4, 178) = 2.55; P = 0.05). The PST subjects also developed more adaptive coping strategies than ST subjects. CONCLUSIONS: We found that PST was not superior to ST at improving vision function in patients with AMD, but that PST improved their vision-related QoL. Despite the benefits of anti-vascular endothelial growth factor treatments, AMD remains associated with disability, depression, and diminished QoL. This clinical reality necessitates new rehabilitative interventions to improve the vision function and QoL of older persons with AMD. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article

Low Vision Depression Prevention Trial in Age-Related Macular Degeneration: A Randomized Clinical Trial.

PURPOSE: To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). DESIGN: Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. PARTICIPANTS: Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). INTERVENTIONS: Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. MAIN OUTCOME MEASURES: The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire-25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). RESULTS: At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27-1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27-0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. CONCLUSIONS: An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid depression will increase. Promoting interactions between ophthalmology, optometry, rehabilitation, psychiatry, and behavioral psychology may prevent depression in this population

The effect of Gonioscopy on keratometry and corneal surface topography

BACKGROUND: Biometric procedures such as keratometry performed shortly after contact procedures like gonioscopy and applanation tonometry could affect the validity of the measurement. This study was conducted to understand the short-term effect of gonioscopy on corneal curvature measurements and surface topography based Simulated Keratometry and whether this would alter the power of an intraocular lens implant calculated using post-gonioscopy measurements. We further compared the effect of the 2-mirror (Goldmann) and the 4-mirror (Sussman) Gonioscopes. METHODS: A prospective clinic-based self-controlled comparative study. 198 eyes of 99 patients, above 50 years of age, were studied. Exclusion criteria included documented dry eye, history of ocular surgery or trauma, diabetes mellitus and connective tissue disorders. Auto-Keratometry and corneal topography measurements were obtained at baseline and at three follow-up times – within the first 5 minutes, between the 10(th)-15(th )minute and between the 20(th)-25(th )minute after intervention. One eye was randomized for intervention with the 2-mirror gonioscope and the other underwent the 4-mirror after baseline measurements. t-tests were used to examine differences between interventions and between the measurement methods. The sample size was calculated using an estimate of clinically significant lens implant power changes based on the SRK-II formula. RESULTS: Clinically and statistically significant steepening was observed in the first 5 minutes and in the 10–15 minute interval using topography-based Sim K. These changes were not present with the Auto-Keratometer measurements. Although changes from baseline were noted between 20 and 25 minutes topographically, these were not clinically or statistically significant. There was no significant difference between the two types of gonioscopes. There was greater variability in the changes from baseline using the topography-based Sim K readings. CONCLUSION: Reversible steepening of the central corneal surface is produced by the act of gonioscopy as measured by Sim K, whereas no significant differences were present with Auto-K measurements. The type of Gonioscope used does not appear to influence these results. If topographically derived Sim K is used to calculate the power of the intraocular lens implant, we recommend waiting a minimum of 20 minutes before measuring the corneal curvature after gonioscopy with either Goldmann or Sussman contact lenses

Interpretation of ambiguous situations: evidence for a dissociation between social and physical threat in Williams syndrome

There is increasing evidence that Williams syndrome (WS) is associated with elevated anxiety that is non-social in nature, including generalised anxiety and fears. To date very little research has examined the cognitive processes associated with this anxiety. In the present research, attentional bias for non-social threatening images in WS was examined using a dot-probe paradigm. Participants were 16 individuals with WS aged between 13 and 34 years and two groups of typically developing controls matched to the WS group on chronological age and attentional control ability respectively. The WS group exhibited a significant attention bias towards threatening images. In contrast, no bias was found for group matched on attentional control and a slight bias away from threat was found in the chronological age matched group. The results are contrasted with recent findings suggesting that individuals with WS do not show an attention bias for threatening faces and discussed in relation to neuroimaging research showing elevated amygdala activation in response to threatening non-social scenes in WS

The emergence of the brain non-CpG methylation system in vertebrates

Mammalian brains feature exceptionally high levels of non-CpG DNA methylation alongside the canonical form of CpG methylation. Non-CpG methylation plays a critical regulatory role in cognitive function, which is mediated by the binding of MeCP2, the transcriptional regulator that when mutated causes Rett syndrome. However, it is unclear whether the non-CpG neural methylation system is restricted to mammalian species with complex cognitive abilities or has deeper evolutionary origins. To test this, we investigated brain DNA methylation across 12 distantly related animal lineages, revealing that non-CpG methylation is restricted to vertebrates. We discovered that in vertebrates, non-CpG methylation is enriched within a highly conserved set of developmental genes transcriptionally repressed in adult brains, indicating that it demarcates a deeply conserved regulatory program. We also found that the writer of non-CpG methylation, DNMT3A, and the reader, MeCP2, originated at the onset of vertebrates as a result of the ancestral vertebrate whole-genome duplication. Together, we demonstrate how this novel layer of epigenetic information assembled at the root of vertebrates and gained new regulatory roles independent of the ancestral form of the canonical CpG methylation. This suggests that the emergence of non-CpG methylation may have fostered the evolution of sophisticated cognitive abilities found in the vertebrate lineage.This work was supported by the Australian Research Council (ARC) Centre of Excellence programme in Plant Energy Biology (grant no. CE140100008). R.L. was supported by a Sylvia and Charles Viertel Senior Medical Research Fellowship, ARC Future Fellowship (no. FT120100862) and Howard Hughes Medical Institute International Research Scholarship. A.d.M. was funded by an EMBO long-term fellowship (no. ALTF 144-2014). J.L.G.-S. was supported by the Spanish government (grant no. BFU2016- 74961-P) and the institutional grant Unidad de Excelencia María de Maeztu (no. MDM-2016-0687). B.V. was supported by the Biomedical Research Council of the Agency for Science, Technology and Research of Singapore. F.G. was supported by an ARC Future Fellowship (no. FT160100267). C.W.R. was supported by an NSF grant (no. IOS-1354898). J.R.E. is an investigator of the Howard Hughes Medical Institute. Genomic data was generated at the Australian Cancer Research Foundation Centre for Advanced Cancer Genomics

Activity loss is associated with cognitive decline in age-related macular degeneration.

BACKGROUND/METHODS: The objective of this study was to determine whether relinquishing cognitive, physical, and social activities is associated with an increased risk of cognitive decline in patients with age-related macular degeneration (AMD). We conducted a 3-year longitudinal study of 206 nondemented patients with AMD. RESULTS: Twenty-three subjects (14.4%) declined cognitively. Age, sex, education, decline in visual acuity, and number of dropped activities were associated with cognitive decline; each additional dropped activity increased the risk by 58%. Subjects who relinquished three activities were 3.87 times (95% confidence interval, 1.95-7.76) more likely to become demented than subjects who relinquished no activities; those who relinquished five activities were 9.54 times (95% confidence interval, 3.05-30.43) more likely. A multivariate model demonstrated that number of dropped activities was a powerful predictor of cognitive decline after controlling for relevant risk factors, particularly for subjects younger than 80 years of age. CONCLUSIONS: Relinquishing valued activities is associated with an increased risk of cognitive decline in older patients with vision loss caused by AMD. These data suggest the importance of promoting optimal cognitive and physical health in patients with AMD and perhaps other chronic diseases