Function and Regulation of Cytochrome P450 4V2 and the Implications in Bietti’s Crystalline Dystrophy

Thesis (Ph.D.)--University of Washington, 2016-06

Epidemiology of open- and closed-globe trauma presenting to Cairns Base Hospital, Queensland

Purpose: To review the epidemiology of serious ocular trauma presenting to Cairns Base Hospital, from the far north Queensland health districts. Methods: A retrospective study of cases from January 1995 to November 2002 inclusive. Cases were analysed with respect to demographics, cause and nature of injury, method of transport and time to and type of ophthalmic treatment, and visual outcomes. Results: There were 226 cases identified, including 71 open-globe and 155 closed-globe injuries. The annual rate of injury was 3.7 per 100 000 for open-globe and 11.8 per 100 000 in total. The Aboriginal and Torres Strait Islander population from the far north Queensland districts showed a disproportionate incidence, with 38% of the total number of injuries, despite representing only 12.3% of the population. Assault in the Aboriginal and Torres Strait Islander population resulted in 69.6% of injuries in men and 75.8% of injuries in women. Of all assaults 76.2% were alcohol-related. The majority (71.5%) of injuries in the Caucasian population were due to accidental blunt and sharp trauma. In total, 77.4% of injuries occurred in men, with an average age of 31 years. Of all open and closed injuries in the study, a final visual acuity of 6/12 or better was achieved in 47.8% of eyes and a final visual acuity of 6/60 or less occurred in 17.7% of patients, 20.8% patients were lost to follow up. In total, 14.1% of open injuries required enucleation/evisceration. Conclusions: The incidence of ocular trauma in far north Queensland is equal to other Australian populations. However, there is a disproportionately high incidence in the Aboriginal and Torres Strait Islander population. Alcohol-related assault is a significant cause of visual loss in the Aboriginal and Torres Strait Islander population. Closed-globe injuries are more common than open globe; however, the latter have poorer visual prognosis. Initial visual acuity of all injuries correlated with final visual acuity.

Prognostic indicators for open globe injury

Background: The purpose of the study is to identify factors predictive of outcome after open globe injury in 273 patients admitted to the Royal Brisbane Hospital, Queensland, Australia between 1992 and 2003. Methods: Data were collected retrospectively regarding demographic and geographical factors, injury circumstances, initial visual acuity (VA), injury parameters, details of initial and subsequent surgery, final best corrected VA and complications. Multivariate analysis using binary logistic regression was utilized to identify which factors were related to outcome. Results: 83% of patients were male, with a mean age of 38.3 years. The mean duration of follow up was 16.6 months and 58% of patients (135 of 231) achieved an overall improvement in their vision. Forty-one cases (15%) were enucleated, with half of these cases performed primarily. The prognostic factors indicating the likelihood of a VA of counting fingers or worse were poor initial VA, a large laceration > 10 mm and the presence of a relative afferent pupil defect. Rural patients had a significantly worse final VA than city dwellers and had higher rates of endophthalmitis and enucleation. Conclusions: Assessment of prognostic factors at the time of presentation of an open globe injury enables realistic expectations of final visual outcome by the doctor and the patient. In order to improve outcomes in patients from rural areas, access to specialized eye services need to be upgraded.

Local edge detectors: A substrate for fine spatial vision at low temporal frequencies in rabbit retina

Visual acuity is limited by the size and density of the smallest retinal ganglion cells, which correspond to the midget ganglion cells in primate retina and the beta- ganglion cells in cat retina, both of which have concentric receptive fields that respond at either light- On or light- Off. In contrast, the smallest ganglion cells in the rabbit retina are the local edge detectors ( LEDs), which respond to spot illumination at both light- On and light- Off. However, the LEDs do not predominate in the rabbit retina and the question arises, what role do they play in fine spatial vision? We studied the morphology and physiology of LEDs in the isolated rabbit retina and examined how their response properties are shaped by the excitatory and inhibitory inputs. Although the LEDs comprise only similar to 15% of the ganglion cells, neighboring LEDs are separated by 30 - 40 mu m on the visual streak, which is sufficient to account for the grating acuity of the rabbit. The spatial and temporal receptive- field properties of LEDs are generated by distinct inhibitory mechanisms. The strong inhibitory surround acts presynaptically to suppress both the excitation and the inhibition elicited by center stimulation. The temporal properties, characterized by sluggish onset, sustained firing, and low bandwidth, are mediated by the temporal properties of the bipolar cells and by postsynaptic interactions between the excitatory and inhibitory inputs. We propose that the LEDs signal fine spatial detail during visual fixation, when high temporal frequencies are minimal.

+Psychometric evaluation of the MacDQoL individualised measure of the impact of macular degeneration on quality of life

Background: The MacDQoL is an individualised measure of the impact of macular degeneration (MD) on quality of life (QoL). There is preliminary evidence of its psychometric properties and sensitivity to severity of MD. The aim of this study was to carry out further psychometric evaluation with a larger sample and investigate the measure's sensitivity to MD severity. Methods: Patients with MD (n = 156: 99 women, 57 men, mean age 79 ± 13 years), recruited from eye clinics (one NHS, one private) completed the MacDQoL by telephone interview and later underwent a clinic vision assessment including near and distance visual acuity (VA), comfortable near VA, contrast sensitivity, colour recognition, recovery from glare and presence or absence of distortion or scotoma in the central 10° of the visual field. Results: The completion rate for the MacDQoL items was 99.8%. Of the 26 items, three were dropped from the measure due to redundancy. A fourth was retained in the questionnaire but excluded when computing the scale score. Principal components analysis and Cronbach's alpha (0.944) supported combining the remaining 22 items in a single scale. Lower MacDQoL scores, indicating more negative impact of MD on QoL, were associated with poorer distance VA (better eye r = -0.431 p < 0.001; worse eye r = -0.350 p < 0.001; binocular vision r = -0.419 p < 0.001) and near VA (better eye r -0.326 p < 0.001; worse eye r = -0.226 p < 0.001; binocular vision r = -0.326 p < 0.001). Poorer MacDQoL scores were associated with poorer contrast sensitivity (better eye r = 0.392 p < 0.001; binocular vision r = 0.423 p < 0.001), poorer colour recognition (r = 0.417 p < 0.001) and poorer comfortable near VA (r = -0.283, p < 0.001). The MacDQoL differentiated between those with and without binocular scotoma (U = 1244 p < 0.001). Conclusion: The MacDQoL 22-item scale has excellent internal consistency reliability and a single-factor structure. The measure is acceptable to respondents and the generic QoL item, MD-specific QoL item and average weighted impact score are related to several measures of vision. The MacDQoL demonstrates that MD has considerable negative impact on many aspects of QoL, particularly independence, leisure activities, dealing with personal affairs and mobility. The measure may be valuable for use in clinical trials and routine clinical care. © 2005 Mitchell et al; licensee BioMed Central Ltd.

Effect of uncorrected astigmatism on vision

PURPOSE: To examine the effect of uncorrected astigmatism in older adults. SETTING: University Vision Clinic METHOD: Twenty-one healthy presbyopes, aged 58.9±2.8 years, had astigmatism of 0.0 to -4.0 x 90?DC and -3.0DC of cylinder at 90?, 180? and 45? induced with spectacle lenses, with the mean spherical equivalent compensated to plano, in random order. Visual acuity was assessed binocularly using a computerised test chart at 95%, 50% and 10% contrast. Near acuity and reading speed were measured using standardised reading texts. Light scatter was quantified with the cQuant and driving reaction times with a computer simulator. Finally visual clarity of a mobile phone and computer screen was subjectively rated. RESULTS: Distance visual acuity decreased with increasing uncorrected astigmatic power (F=174.50, p<0.001) and was reduced at lower contrasts (F=170.77, p<0.001). Near visual acuity and reading speed also decreased with increasing uncorrected astigmatism power (p<0.001). Light scatter was not significantly affected by uncorrected astigmatism (p>0.05), but the reliability and variability of measurements decreased with increasing uncorrected astigmatic power (p<0.05). Driving simulator performance was also unaffected by uncorrected astigmatism (p>0.05), but subjective rating of clarity decreased with increasing uncorrected astigmatic power (p<0.001). Uncorrected astigmatism at 45? or 180? orientation resulted in a worse distance and near visual acuity, and subjective rated clarity than 90? orientation (p<0.05). CONCLUSION: Uncorrected astigmatism, even as low as 1.0DC, causes a significant burden on a patient’s vision. If left uncorrected, this could impact significantly on their independence, quality of life and wellbeing.

Childhood ethnic differences in ametropia and ocular biometry:the Aston Eye Study

Purpose: To describe the methodology, sampling strategy and preliminary results for the Aston Eye Study (AES), a cross-sectional study to determine the prevalence of refractive error and its associated ocular biometry in a large multi-racial sample of school children from the metropolitan area of Birmingham, England. Methods: A target sample of 1700 children aged 6–7 years and 1200 aged 12–13 years is being selected from Birmingham schools selected randomly with stratification by area deprivation index (a measure of socio-economic status). Schools with pupils predominantly (>70%) from a single race are excluded. Sample size calculations account for the likely participation rate and the clustering of individuals within schools. Procedures involve standardised protocols to allow for comparison with international population-based data. Visual acuity, non-contact ocular biometry (axial length, corneal radius of curvature and anterior chamber depth) and cycloplegic autorefraction are measured in both eyes. Distance and near oculomotor balance, height and weight are also assessed. Questionnaires for parents and older children will allow the influence of environmental factors on refractive error to be examined. Results: Recruitment and data collection are ongoing (currently N = 655). Preliminary cross-sectional data on 213 South Asian, 44 black African Caribbean and 70 white European children aged 6–7 years and 114 South Asian, 40 black African Caribbean and 115 white European children aged 12–13 years found myopia prevalence of 9.4% and 29.4% for the two age groups respectively. A more negative mean spherical equivalent refraction (SER) was observed in older children (-0.21 D vs +0.87 D). Ethnic differences in myopia prevalence are emerging with South Asian children having higher levels than white European children 36.8% vs 18.6% (for the older children). Axial length, corneal radius of curvature and anterior chamber depth were normally distributed, while SER was leptokurtic (p < 0.001) with a slight negative skew. Conclusions: The AES will allow ethnic differences in the ocular characteristics of children from a large metropolitan area of the UK to be examined. The findings to date indicate the emergence of higher levels of myopia by early adolescence in second and third generation British South Asians, compared to white European children. The continuation of the AES will allow the early determinants of these ethnic differences to be studied.

Sampling and measurement methods for a study of childhood refractive error in a UK population

Background There is a paucity of data describing the prevalence of childhood refractive error in the United Kingdom. The Northern Ireland Childhood Errors of Refraction study, along with its sister study the Aston Eye Study, are the first population-based surveys of children using both random cluster sampling and cycloplegic autorefraction to quantify levels of refractive error in the United Kingdom. Methods Children aged 6–7 years and 12–13 years were recruited from a stratified random sample of primary and post-primary schools, representative of the population of Northern Ireland as a whole. Measurements included assessment of visual acuity, oculomotor balance, ocular biometry and cycloplegic binocular open-field autorefraction. Questionnaires were used to identify putative risk factors for refractive error. Results 399 (57%) of 6–7 years and 669 (60%) of 12–13 years participated. School participation rates did not vary statistically significantly with the size of the school, whether the school is urban or rural, or whether it is in a deprived/non-deprived area. The gender balance, ethnicity and type of schooling of participants are reflective of the Northern Ireland population. Conclusions The study design, sample size and methodology will ensure accurate measures of the prevalence of refractive errors in the target population and will facilitate comparisons with other population-based refractive data.

Effect of age related macular degeneration on the Eger macular stressometer photostress recovery time

Aim: To assess the repeatability of Eger macular stressometer (EMS) measures of photostress recovery and determine their association with other measures of visual function. Methods: EMS photostress recovery time was measured in 90 patients with bilateral exudative age related macular degeneration (AMD), 19 with bilateral atrophic AMD and 47 with both forms of the condition (mean age 79 (SD 13) years). Measurements were made on two occasions separated by 1 year. Intrasession repeatability was assessed by repeating the measures after a 10 minute recovery period at the first visit. Distance visual acuity was measured with a logMAR chart, near visual acuity with a MNRead chart at 25 cm, contrast sensitivity with a Pelli-Robson chart, and the presence of central visual disturbance assessed with an Amsler grid. A questionnaire was used to assess self reported difficulties with glare recovery. Results: The average EMS recovery time was 11.0 (SD 8.9) seconds, decreasing by 1.6 (5.2) seconds on repeated measurement (p<0.05). EMS photostress recovery was not correlated with visual function measures or subjective difficulties with lights (p>0.05). EMS photostress recovery time did not predict those whose vision decreased over the following year compared with those among whom it remained stable. Conclusions: The EMS test is not a useful tool in determining the severity or progression of AMD.

Development of a questionnaire to assess the relative subjective benefits of presbyopia correction

Purpose To develop a standardized questionnaire of near visual function and satisfaction to complement visual function evaluations of presbyopic corrections. Setting Eye Clinic, School of Life and Health Sciences, Aston University, Midland Eye Institute and Solihull Hospital, Birmingham, United Kingdom. Design Questionnaire development. Methods A preliminary 26-item questionnaire of previously used near visual function items was completed by patients with monofocal intraocular lenses (IOLs), multifocal IOLs, accommodating IOLs, multifocal contact lenses, or varifocal spectacles. Rasch analysis was used for item reduction, after which internal and test–retest reliabilities were determined. Construct validity was determined by correlating the resulting Near Activity Visual Questionnaire (NAVQ) scores with near visual acuity and critical print size (CPS), which was measured using the Minnesota Low Vision Reading Test chart. Discrimination ability was assessed through receiver-operating characteristic (ROC) curve analysis. Results One hundred fifty patients completed the questionnaire. Item reduction resulted in a 10-item NAVQ with excellent separation (2.92), internal consistency (Cronbach a = 0.95), and test–retest reliability (intraclass correlation coefficient = 0.72). Correlations of questionnaire scores with near visual acuity (r = 0.32) and CPS (r = 0.27) provided evidence of validity, and discrimination ability was excellent (area under ROC curve = 0.91). Conclusion Results show the NAVQ is a reliable, valid instrument that can be incorporated into the evaluation of presbyopic corrections.

Carotenoids and ocular disease: a review

Background: Carotenoids are not considered to be essential nutrients, but their antioxidant and photoprotective properties have prompted interest in their potential role in disease prevention. Our aim is to review the evidence In relation to ocular disease. Method: Web of Science and Medline via PubMed database search. Results Lutein and zeaxanthin intake has been associated with a 22% reduced risk of cataract extraction in women (RR 0.78, p = 0.04), and a 19% lower risk of cataract in men (RR 0.8, p = 0, 03). A randomised controlled trial (RCT) found a significant improvement in visual acuity in cataract patients supplemented with lutein. Two RCTs investigating the effect of P-carotene, in combination with other nutrients, on cataract report conflicting results. Several studies show no inverse association between cataract and P-carotene. Lutein and zeaxanthin are the only carotenoids found in the human macula. RCTs have found beneficial effects of both lutein and beta-carotene supplementation, in combination with other antioxidants, on visual function age-related macular disease affected subjects. Evidence for a role of lutein in preventing deterioration of visual function in retinitis pigmentosa patients is conflicting. CONCLUSIONS: Further research into the role of lutein and zeaxanthin in prevention of onset and progression of ocular disease is warranted.

Reading performance with various lamps in age-related macular degeneration

The purpose of this study was to determine if there was an objective difference in reading between four commonly available lamps, of varying spectral radiance, for 13 subjects with age-related maculopathy (ARM) or non-exudative age-related macular degeneration (AMD) - logMAR visual acuity between 0.04 and 0.68. At a constant illuminance of 2000 lux, there was no interaction between ARM and AMD subgroups and no statistically significant difference between the lamps: standard (clear envelope) incandescent, daylight simulation (blue tint envelope) incandescent, compact fluorescent and halogen incandescent, for any reading outcome measure (threshold print size p = 0.67, critical print size p = 0.74, acuity reserve p = 0.84 and mean reading rate p = 0.78). For lamps typically used in low-vision rehabilitation, a clinically significant effect of spectral radiance on reading for people with ARM or non-exudative AMD is unlikely. © 2007 The College of Optometrists.

Optimizing measurement of subjective amplitude of accommodation with defocus curves

PURPOSE: To determine whether letter sequences and/or lens-presentation order should be randomized when measuring defocus curves and to assess the most appropriate criterion for calculating the subjective amplitude of accommodation (AoA) from defocus curves. SETTING: Eye Clinic, School of Life & Health Sciences, Aston University, Birmingham, United Kingdom. METHODS: Defocus curves (from +3.00 diopters [D] to -3.00 D in 0.50 D steps) for 6 possible combinations of randomized or nonrandomized letter sequences and/or lens-presentation order were measured in a random order in 20 presbyopic subjects. Subjective AoA was calculated from the defocus curves by curve fitting using various published criteria, and each was correlated to subjective push-up AoA. Objective AoA was measured for comparison of blur tolerance and pupil size. RESULTS: Randomization of lens-presentation order and/or letter sequences, or lack of, did not affect the measured defocus curves (P>.05, analysis of variance). The range of defocus that maintains highest achievable visual acuity (allowing for variability of repeated measurement) was better correlated to (r = 0.84) and agreed best with ( 0.50 D) subjective push-up AoA than any other relative or absolute acuity criterion used in previous studies. CONCLUSIONS: Nonrandomized letters and lens presentation on their own did not affect subjective AoA measured by defocus curves, although their combination should be avoided. Quantification of subjective AoA from defocus curves should be standardized to the range of defocus that maintains the best achievable visual acuity.

The MacDQoL individualized measure of the impact of macular degeneration on quality of life: reliability and responsiveness

PURPOSE: To investigate the MacDQoL test-retest reliability and sensitivity to change in vision over a period of one year in a sample of patients with age-related macular degeneration (AMD). DESIGN: A prospective, observational study. METHOD: Patients with AMD from an ophthalmologist's list (n = 135) completed the MacDQoL questionnaire by telephone interview and underwent a vision assessment on two occasions, one year apart. RESULTS: Among participants whose vision was stable over one year (n = 87), MacDQoL scores at baseline and follow-up were highly correlated (r = 0.95; P < .0001). Twelve of the 22 scale items had intraclass correlations of >.80; only two were correlated <.7. There was no difference between baseline and follow-up scores (P = .85), indicating excellent test-retest reliability. Poorer quality of life (QoL) at follow-up, measured by the MacDQoL present QoL overview item, was associated with deterioration in both the better eye and binocular distance visual acuity [VA] (r = 0.29; P = .001, r = 0.21; P = .016, respectively; n = 135). There was a positive correlation between deterioration in the Mac. DQoL average weighted impact score and deterioration in both binocular near VA and reading speed (r = 0.20; P = .019, r = 0.18; P = .041, respectively; n = 135). CONCLUSION: The MacDQoL has excellent test-retest reliability. Its sensitivity to change in vision status was demonstrated in correlational analyses. The measure indicates that the negative impact of AMD on QoL increases with increasing severity of visual impairment.

The significance of hand wash compliance on the transfer of dermal lipids in contact lens wear

Aim: The aim of this study was to assess the impact of hand washing regimes on lipid transference to contact lenses. The presence of lipids on contact lenses can affect visual acuity and enhance spoilation. Additionally, they may even mediate and foster microbial transfer and serve as a marker of potential dermal contamination. Methods and materials: A social hand wash and the Royal College of Nursing (RCN) hand wash were investigated. A 'no-wash regime' was used as control. The transfer of lipids from the hand was assessed by Thin Layer Chromatography (TLC). Lipid transference to the contact lenses was studied through fluorescence spectroscopy (FS). Results: Iodine staining, for presence of lipids, on TLC plates indicated the 'no-wash regime' score averaged at 3.4 ± 0.8, the social wash averaged at 2.2 ± 0.9 and the RCN averaged at 1.2 ± 0.3 on a scale of 1-4. The FS of lipids on contact lenses for 'no washing' presented an average of 28.47 ± 10.54 fluorescence units (FU), the social wash presented an average of 13.52 ± 11.12. FU and the RCN wash presented a much lower average 6.47 ± 4.26. FU. Conclusions: This work demonstrates how the method used for washing the hands can affect the concentration of lipids, and the transfer of these lipids onto contact lenses. A regime of hand washing for contact lens users should be standardised to help reduce potentially transferable species present on the hands. © 2011 British Contact Lens Association.