Visual field and structural alterations in age-related macular degeneration

The thesis investigated progression of the central 10° visual field with structural changes at the macula in a cross-section of patients with varying degrees of agerelated macular degeneration (AMD). The relationships between structure and function were investigated for both standard and short-wavelength automated perimetry (SWAP). Factors known to influence the measure of visual field progression were considered, including the accuracy of the refractive correction on SWAP thresholds and the learning effect. Techniques of assessing the structure to function relationships between fundus images and the visual field were developed with computer programming and evaluated for repeatability. Drusen quantification of fundus photographs and retro-mode scanning laser ophthalmoscopic images was performed. Visual field progression was related to structural changes derived from both manual and automated methods. Principal Findings: • Visual field sensitivity declined with advancing stage of AMD. SWAP showed greater sensitivity to progressive changes than standard perimetry. • Defects were confined to the central 5°. SWAP defects occurred at similar locations but were deeper and wider than corresponding standard perimetry defects. • The central field became less uniform as severity of AMD increased. SWAP visual field indices of focal loss were of more importance when detecting early change in AMD, than indices of diffuse loss. • The decline in visual field sensitivity over stage of severity of AMD was not uniform, whereas a linear relationship was found between the automated measure of drusen area and visual field parameters. • Perimetry exhibited a stronger relationship with drusen area than other measures of visual function. • Overcorrection of the refraction for the working distance in SWAP should be avoided in subjects with insufficient accommodative facility. • The perimetric learning effect in the 10° field did not differ significantly between normal subjects and AMD patients. • Subretinal deposits appeared more numerous in retro-mode imaging than in fundus photography

Early Development of Vaginal Microbicides to Decrease HIV Acquisition in Women

Women are disproportionately affected by HIV, with most infections in women occurring as a result of heterosexual intercourse. New HIV prevention strategies are needed that women could employ discretely, potentially without consulting male partners. Vaginal spermicidal gels and films can successfully prevent pregnancy, and similar products can be used to deliver antiretroviral medications. This thesis presents two phase 1 studies of vaginal microbicides containing dapivirine or tenofovir and will demonstrate that these products are safe, effective, and successfully deliver their respective antiretrovirals in the vaginal environment. The FAME 02b study describes pharmacokinetic and pharmacodynamic evaluation of a single dose of dapivirine vaginal gel and film. By assessing drug concentrations in plasma, cervicovaginal fluid, and cervical tissue, we show that both vaginal film and gel formulations are able to deliver concentrations of dapivirine to these anatomic locations that should be protective against HIV infection. An explant HIV infectivity assay performed on cervical tissue biopsy specimens supports the further development of both dapivirine products. The FAME 05 study employs a complementary design to FAME 02b to evaluate similar film and gel products containing tenofovir. The same schedule and type of samples were collected following a single dose of tenofovir vaginal film or gel, including the cervical tissue explant assay, with the addition of rectal fluid drug concentration. Tenofovir film was associated with higher drug concentrations in plasma, cervicovaginal fluid, and cervical tissue, while rectal fluid tenofovir was higher after gel dosing. There was no difference between the two products in preventing cervical tissue explant HIV infection. Early studies of both oral and vaginal pre-exposure prophylaxis against HIV were promising, finding up to 70% protection from HIV acquisition when products were used consistently. Follow-up randomized clinical trials failed to confirm the protective effect of either form of PrEP among women, partly due to poor product adherence. New vaginal microbicides that can be used episodically around the time of intercourse may be more preferable to some women than a daily preventive medication. Clinical trials of dapivirine and tenofovir vaginal gels and films are warranted in order to provide a variety of HIV prevention strategies

Visual field and structural alterations in age-related macular degeneration

The thesis investigated progression of the central 10° visual field with structural changes at the macula in a cross-section of patients with varying degrees of agerelated macular degeneration (AMD). The relationships between structure and function were investigated for both standard and short-wavelength automated perimetry (SWAP). Factors known to influence the measure of visual field progression were considered, including the accuracy of the refractive correction on SWAP thresholds and the learning effect. Techniques of assessing the structure to function relationships between fundus images and the visual field were developed with computer programming and evaluated for repeatability. Drusen quantification of fundus photographs and retro-mode scanning laser ophthalmoscopic images was performed. Visual field progression was related to structural changes derived from both manual and automated methods. Principal Findings: • Visual field sensitivity declined with advancing stage of AMD. SWAP showed greater sensitivity to progressive changes than standard perimetry. • Defects were confined to the central 5°. SWAP defects occurred at similar locations but were deeper and wider than corresponding standard perimetry defects. • The central field became less uniform as severity of AMD increased. SWAP visual field indices of focal loss were of more importance when detecting early change in AMD, than indices of diffuse loss. • The decline in visual field sensitivity over stage of severity of AMD was not uniform, whereas a linear relationship was found between the automated measure of drusen area and visual field parameters. • Perimetry exhibited a stronger relationship with drusen area than other measures of visual function. • Overcorrection of the refraction for the working distance in SWAP should be avoided in subjects with insufficient accommodative facility. • The perimetric learning effect in the 10° field did not differ significantly between normal subjects and AMD patients. • Subretinal deposits appeared more numerous in retro-mode imaging than in fundus photography.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Clinical evaluation of the Macuscope macular pigment densitometer

Background/aims. The MacuScope uses a psychophysical technique called heterochromic flicker photometry to measure macular pigment optical density (MPOD). Our aim was to determine the measurement variability (noise) of the MacuScope. Methods. Thirty-eight normally sighted participants who ranged in age from 19 to 46 years (25.7±7.6 years) were recruited from staff and students of Aston University. Data were collected by two operators, HB and JA, in two sessions separated by 1 week in order to assess test repeatability and reproducibility. Results. The overall mean MPOD for the cohort was 0.47±0.14. There was a significant negative correlation between MacuScope MPOD readings and age (r=-0.368, p=0.023). Coefficients were 0.45 and 0.58 for repeatability, and 0.49 and 0.36 for reproducibility. For each pair of results, there was a significant positive correlation between mean and difference MPOD values. Conclusions. If MPOD is being monitored over time then any change less than 0.58 units should not be considered clinically significant as it is very likely to be due to instrument noise. The size of the coefficient appears to be positively correlated with MPOD

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

Microperimetry and multimodal imaging in polypoidal choroidal vasculopathy

Polypoidal choroidal vasculopathy (PCV) is a degenerative macular disease. The study determined the topographical concordance in the areal extent of PCV, defined by indocyanine green angiography (ICGA), and the corresponding outcomes from spectral-domain optical coherence tomography (SD-OCT) and microperimetry, in 25 individuals (25 eyes) who had undergone 3 months of anti-vascular endothelial growth factor treatment. The differential light sensitivity within 10° eccentricity was evaluated by Pattern Deviation probability analysis. The concordances and proportional areal extents of the abnormality for ICGA, SD-OCT and microperimetry were compared. The concordance in the areal extent between all three modalities was 59%. The median concordance between ICGA and microperimetry was 60%; between ICGA and SD-OCT, 70%; and between SD-OCT and microperimetry, 72%. SD-OCT and microperimetry each identified a greater areal extent (>20%) compared to ICGA in 13 and 19 eyes, respectively. A greater areal extent (>20%) was present in 9 eyes for microperimetry compared to SD-OCT and in 5 eyes for SD-OCT compared to microperimetry. SD-OCT and microperimetry each identified a greater area of abnormality than ICGA which supports the clinical utility of SD-OCT. Strong concordance was present between SD-OCT and microperimetry; however, microperimetry identified additional areas of functional abnormality

Barriers to integrating routine depression screening into community low vision rehabilitation services: a mixed methods study

Background:Undetected depression is common in people withlow vision and depression screening has beenrecommended. However, depression screening is a complex procedure for which low vision practitioners need training. Thisstudy examined the integration of routine depression screening, using two questions, and referral pathways into a nationallow vision service in Wales at 6 months following practitioner training, and identified key barriers to implementation.Methods:This pre-post single group study employed a convergent mixed methods design to collect quantitativequestionnaire and qualitative interview data on low vision practitioners’clinical practice and perceived barriers toimplementing depression screening. Forty practitioners completed questionnaires pre-, immediately post- and 6 monthspost-training and nine engaged in interviews 6 months post-training. Ordinal questionnaire scores were Rasch-transformedinto interval-level data before linear regression analyses were performed to determine the change in scores over time andthe association between perceived barriers and clinical practice. Thematic Analysis was applied to the interviews and thenarrative results merged withthe questionnaire findings.Results:Before training, only one third of practitioners (n= 15) identified depression in low vision patients, increasing toover 90% (n= 37) at 6 months post-training, with a corresponding increase in those using validated depression screeningquestions from 10% (n= 4) to 80% (n= 32). Six months post-training, practitioners reported taking significantly moreaction in response to suspected depression (difference in means = 2.77, 95% CI 1.93 to 3.61,p< 0.001) and perceived lessbarriers to addressing depression (difference in means =−0.95, 95% CI−1.32 to−0.59,p<0.001).However,thescreening questions were not used consistently. Some barriers to implementation remained, including perceived patientreluctance to discuss depression, time constraints and lack of confidence in addressing depression.Conclusions:The introduction of depression screening service guidelines and training successfully increased the numberof low vision practitioners identifying and addressing depression. However, standardized screening of all low visionattendees has not yet been achieved and several barriers remain. Healthcare services need to address these barriers whenconsidering mental health screening, and further research could focus on the process from the patients’perspective, todetermine the desire for and acceptability of screening

Factors influencing the prescribing behaviour of independent prescriber optometrists:a qualitative study using the Theoretical Domains Framework

Purpose Whilst the number of independent prescriber (IP) optometrists in the United Kingdom is increasing, there is limited evidence describing the experiences of these individuals. The Theoretical Domains Framework (TDF) provides an evidence‐based approach to understand determinants of behaviour. This conceptual framework can enable mapping to the COM‐B behaviour change model and the wider Behaviour Change Wheel to develop interventions to optimise behaviour‐change and healthcare processes more systematically. The study aimed to use the TDF to identify the factors that influence independent prescribing behaviour, and to map these findings to the COM‐B system to elucidate the relevant intervention functions, in order to identify the support required by optometrist prescribers. Methods Using a qualitative design, semi‐structured interviews based on the TDF were undertaken with independent prescriber optometrists. Thematic analysis was used to identify themes inductively, which were then deductively mapped to the TDF and linked to the COM‐B. Results Sixteen participants (9 male, 7 female; median age 45 years, range 28–65 years), based in community (n = 10) and hospital (n = 6) settings, were interviewed. Eleven of the TDF domains were found to influence prescribing behaviour. Findings highlighted the need for good communication with patients (TDF domain: Skills, COM‐B: Capability); confidence (TDF domain: Beliefs about capabilities, COM‐B: Motivation); good networks and relationships with other healthcare professionals, e.g., general practitioners (TDF domain: Social influences, COM‐B: Opportunity; TDF domain: Social/professional role and identity, COM‐B: Motivation); the need for appropriate structure for remuneration (TDF domain: Reinforcement, COM‐B: Motivation; TDF domain: Social/professional role and identity, COM‐B: Motivation) and the provision of professional guidelines (TDF domain: Knowledge, COM‐B: Capability; TDF domain: Environmental context and resources, COM‐B Opportunity). Conclusions Having identified theory‐derived influencers on prescribing decisions by optometrists, the findings can be used to develop a structured intervention, such as a support package to help optimise prescribing by optometrists, with the ultimate goal of eye care quality improvement