INTRODUCTION Lack of follow-up to recommended appointments can decrease vision outcomes. Research is needed to determine the best approach to scheduling follow-up appointments in the primary eye care setting to help overcome barriers and decrease disparities in vision health. The specific aim of this work is to evaluate the effectiveness of automated and personal telephone interventions to improve follow-up adherence in the primary eye care setting. METHODS In a prospective, single-blind, randomized, controlled trial, 1,095 patients seen in the Cataract and Primary Care service (CPEC) at Wills Eye Hospital who were due for follow-up appointments were randomly assigned to usual care, automated telephone intervention or personal telephone intervention group. Patients in the usual care group (n=364) received a form letter reminding them to make an appointment and an automated reminder phone call one day prior to their scheduled visit. Automated intervention participants (n=365) received the usual care form letter and an automated call 1-month prior to their recommended follow-up date, a mailed appointment reminder if an appointment was scheduled, and an automated telephone reminder the day before the scheduled appointment. If a patient in the automated intervention group did not attend the scheduled appointment, a reminder postcard was sent. Personal intervention participants (n=365) received the traditional form letter and a personal telephone call 1-month prior to the recommended follow-up date, a mailed appointment reminder if an appointment was scheduled, and a personal telephone reminder prior to the scheduled appointment. If a patient in the personal intervention group did not attend the scheduled appointment, they received a personal call. Scheduling and attendance data were extracted from the electronic medical record system. RESULTS Patients in the personal intervention group had greater adherence to follow-up recommendations than patients in the usual care group (37.70% vs. 27.47%; RR: 1.37; CI 1.24-1.52; p<0.001) and automated intervention group (29.59%; RR: 1.27; CI 1.15-1.41; p=0.02). Patients in the usual care group were not significantly different than patients in the automated intervention group in regards to adherence to follow-up recommendations (27.47% vs. 29.59%; RR: 1.08; CI 0.98-1.18; p=0.53). Personal intervention improved adherence for patients who have been previously recognized as at risk including men (37.04% vs. 22.39%; RR: 1.65; CI: 1.41-1.94; p=0.01), African Americans (39.58% vs. 29.52%; RR: 1.34; CI 1.16-1.55; p=0.03), patients under 65 (28.93%-18.67%; RR: 1.55; CI 1.40-1.71; p=0.01), and patients who live greater than 20 miles from Wills Eye Hospital (44.74% vs. 12.50%; RR: 3.58; CI 2.59-4.95; p=0.01). Additionally, personal intervention improved adherence in patients with Medicare (58.42% vs. 43.56%; RR: 1.34; CI 1.01-1.79; p=0.03) and urban patients who live within 2 miles of Wills Eye Hospital (41.18% vs. 17.54%; RR: 2.35; CI 1.81-3.04; p=0.01). As a secondary endpoint, personal intervention significantly improved appointment scheduling over usual care (51.09% vs. 32.14%; RR 1.59; 95% CI 1.33-1.90; p<0.001) and automated intervention (51% vs. 36%; RR: 1.40; CI 1.18-1.66; p<0.001). Automated intervention did not significantly improve appointment scheduling over usual care (36% vs. 32%; RR: 1.13; CI 0.93-1.39; p=0.22). CONCLUSION Personal intervention improved adherence to recommended follow-up for primary eye care appointments overall and in at-risk populations. Automated intervention had no significant improvement over usual care. The cost effectiveness of personal intervention to improve outcomes in a primary ophthalmology setting should be evaluated to determine whether the intervention should be implemented as a process change at Wills Eye Hospital and at other primary ophthalmology care centers.

<p> Existence of a daily circadian rhythm of intraocular pressure (IOP) in pigs has not been previously published, and is a necessary first step to investigate if minipigs could be used as an animal model for glaucoma. Study goals were to (1) investigate the presence of a pattern of rhythmicity to minipig IOP under a regular light/dark cycle, effects of reversing light/dark cycles on (2) immune response and (3) IOP, and if the (4) topical application of Timolol Maleate lowers IOP. </p><p> Eight female Sinclair minipigs were exposed to regular light/dark cycles. Four baseline IOP collections were taken at least 10 days apart. Data collections were 24 hours, with IOP taken from both eyes every two hours using a Reichert Tonopen XL. Light/dark cycles were flipped ten days prior to reversed IOP data collection. Timolol was administered twice a day, for seven days prior to another IOP collection. </p><p> Baseline data were analyzed by repeated measures ANOVA. There was a significant effect of time, F(11,77) = 12.56, <i>p</i> &lt; 0.001. Bonferroni post hoc tests revealed a significant difference between hour 0 and 6, 6 and 10 (the peaks), and between 10 and 14, and 14 and 0 (the troughs). This supports the hypothesis that minipigs have an daily rhythmicity to their IOP. </p><p> Reversed light/dark data were analyzed by mixed measures ANOVA. There was a main effect of time, F(11,143) = 7.503, <i>p</i> &le; 0.001, no main effect of condition (reversed vs baseline), F(1,13) = 1.092, <i> p</i> = 0.315, and an interaction effect (time*reversed vs. baseline), F(11,143) = 5.384, <i>p</i> &lt; 0.001. </p><p> Paired samples t-tests were run on the baseline complete blood cell count (CBC) and the samples taken during the light/dark cycle reversal to investigate if there was an immune response to light/dark cycle reversal. There was a significant effect on several CBC factors; however, none of the factors were out of the &ldquo;normal&rdquo; for female Sinclair Minipigs. </p><p> The final hypothesis was that Timolol Maleate would lower IOP. A mixed ANOVA was run and revealed that there was a main effect of time, F(11,143) = 5.146, <i>p</i> &lt; 0.001, a main effect of condition (baseline vs Timolol), F(1,14) = 6.511, and a significant interaction effect (time*baseline vs Timolol), F(11, 154) = 2.703, <i>p</i> = 0.003. Because the minipigs displays two peaks and two troughs, which has never been seen before, and Timolol had no effect on IOP, further research is needed before pigs can be used as an animal model for glaucoma research.</p><p>

Injury to optic nerve (ON) axons plays a major role in glaucoma progression. ON crush is an established model of axonal injury which results in retrograde degeneration and death of retinal ganglion cells (RGCs). However, it is unknown how signal transmission to higher visual structures such as primary visual cortex (V1) is affected after ON crush. In human glaucoma, visual function is assessed using visual field (VF) tests, but it is also not clear how the test results relate to the disease progression in the retina. Unilateral ON crush was performed on the left eyes of adult C57BL/6 mice. V1 function of the right hemisphere was assessed longitudinally by optical imaging (OI) and in vivo calcium two-photon imaging under anaesthesia before and at 7 days, 14 days and 30 days after ON crush. Human retinas from glaucoma patients were investigated for changes in RGC density and compared to the score from the VF data obtained prior to the patients’ death. ISI and 2P experiments demonstrate a significant shift in OD towards the ipsilateral eye and significant reduction of signal magnitude in V1 in response to contralateral eye stimulation in all ON crush animals. Additionally, response magnitude to ipsilateral eye stimulation was significantly increased after ON crush. While there was significant RGC loss in human glaucoma compared to age matched controls that was correlated to mean VF loss, the scores from the individual VF test points were uncorrelated to RGC density in anatomically equivalent areas. This work demonstrates that unilateral ON crush results in immediate loss of signal transmission from the retina to V1 via a crushed ON. A significant increase of responsiveness in V1 to non-crushed eye stimulation was observed, which indicates that injury of the ON in adulthood may evoke compensatory plasticity in V1.

Autosomal dominant optic atrophy (ADOA) is an inherited optic neuropathy due to mutation in the OPA1 gene. Patients present with bilateral optic nerve head pallor and loss of visual function. Patients also show a reduction in the P50:N95 ratio of the pattern electroretinogram (PERG) and thinning of the retinal nerve fibre layer (RNFL) and macula. In a mouse model of ADOA, previously generated in this laboratory, the defect first manifested as a dendritic pruning of RGCs, which appeared to be ON-centre specific. Electrophysiological evidence in both humans and the mutant mice showed a reduction in the photopic negative component (PhNR) of the brief flash electroretinogram (ERG). The separation of the photopic ERG into ON- and OFF-pathway components using long-duration monochromatic (red) flash on a rod suppressing blue background, provided an opportunity to assess ON- and OFF-RGC function in ADOA, which had not been previously investigated in humans. This study therefore aimed to assess the effect of ADOA on the red-on blue PhNR-ON and PhNR-OFF components to determine whether the PhNR-ON was a selective marker for ADOA. In this thesis, a protocol was developed for recording long duration red-on-blue PhNRs from the macula (focal) and entire retina (full-field). A comparison of the retinotopic characteristics of the PhNRs (brief and long-duration) with the N95 of the PERG and the distribution of RGCs in the retina showed that the PhNR was capable of assessing RGC function. Retinal function was then probed in twelve participants with ADOA and sixteen controls using focal and full-field long duration ERG, full-field brief flash ERG and PERG. Retinal structure was also assessed using optical coherence tomography. In conclusion, this thesis found that the PhNR-ON and PhNR-OFF amplitudes were equally affected with no evidence of a preferential ON-pathway loss.

Keratoconus is a primary cause of visual impairment in young people in the UK. Corneal cross-linking is a recently-introduced treatment for halting progression of keratoconus, which is more effective in early cases. It has long been observed that keratoconus is significantly more prevalent in those with Down’s syndrome (DS) when compared to the general population. Moreover, young people with Down’s syndrome are less able to report early symptoms of keratoconus, often presenting late to eye clinics when cross-linking is no longer possible. A cohort of children and young people with DS were examined with the aim of discovering optometric correlates of keratoconus and to establish the utility of these parameters as risk factors for identifying keratoconus in primary care. An abnormal retinoscopy reflex was found to be the earliest indicator of keratoconus, showing greater potential as a screening test than either refractive error or objective vision measurement. The cornea of individuals with DS is known to be thinner and steeper than usual. Despite this, the high prevalence of keratoconus in DS has long been attributed to eye-rubbing, despite the inherent difference in baseline shape. The current work revealed no relationship between eye rubbing and the development of keratoconus in DS eyes. In vivo biomechanical analysis demonstrated an increased deformation tendency in DS eyes vs. controls, largely accounted for by the decreased corneal thickness in the test group. These results suggest that the high prevalence of keratoconus in DS originates from biomechanical weakness, permitting the loss of regular corneal shape in the absence of eye rubbing. However, ultrastructural analysis of the cornea of the Tc1 mouse model of DS revealed an unaltered collagen and proteoglycan structure. Topographical examination of ‘cone’ morphology in individuals with and without DS demonstrated a similar phenotype at all stages of the disorder, indicating that people with DS and keratoconus may be a useful cohort for future genetic studies into keratoconus as a whole.

Cochlear implants have been shown to successfully restore hearing to the profoundly deaf. Despite this achievement, issues remain concerning the power consumption and the accuracy of stimulation. This thesis is mainly concerned with investigating the spread of stimulation voltage within the cochlea. The power required to generate the stimulus is also investigated, as is the feasibility of powering a fully implanted cochlear implant by harvesting energy from head motion. Several different models have been used to study the voltage distribution within the cochlea due to electrical stimulation from individual electrodes of a cochlear implant. A resistive cable model is first used to illustrate the fall-off of the voltage with distance at the electrode positions along the cochlea. A three-dimensional finite element model of the cochlea is then developed to obtain the voltage distribution at positions closer to the site of neural stimulation. This model is used to demonstrate the way that the voltage distribution varies with the geometry of the cochlea and the electrode array. It was found that placing the return electrode of the implant within the modiolus, as opposed to outside the cochlea, resulted in higher stimulation for the same current input, which reduces the power requirements. The model has also been used to investigate the consequences of a current-steering, or stimulation focussing, strategy that has previously been proposed. A generalisation of this strategy is suggested, whereby impedance information at the neural level, along the path of the spiral ganglion, was used to optimise the focussed voltage distribution at the target neurons. The power consumption of various stimulation strategies is then estimated in order to assess their energy efficiency. Strategies are defined by parameters such as stimulation rate and number of active channels. The feasibility has also been investigated of harvesting electrical energy from head motion, to power a fully-implanted cochlear implant. It was demonstrated that more power could be harvested from higher harmonics but that this would be sensitive to walking speed. The practical approach is to have a heavily damped device that is insensitive.

The cochlea plays an important role in human hearing. Its basic function is to map sounds of different frequencies onto corresponding characteristic positions on the basilar membrane, BM. When sounds enter the fluid-filled cochlea, deflections of the BM occur due to pressure differences between the cochlear fluid chambers. These deflections propagate along the cochlea to a frequency-dependent characteristic position and then decay away rapidly. The mechanics of the cochlea are modelled using both analytic and numerical models. In this thesis, the passive response of the cochlea is analysed, corresponding to its behaviour at high sound levels, to study the fluid coupling and waves in the cochlea. The fluid coupling is studied in 1D and 3D, uniform and non-uniform, uncoiled and coiled geometries, all with a passive basilar membrane. A ‘uniaxial model’, which is dependent on only a single dimension, is developed to represent the three-dimensional cochlea. The finite element method is also used to provide an independent check of the results from the analytic model. Analytic methods are used to predict waves due to different mechanisms in the passive cochlea, such as 1D and 3D fluid coupling and longitudinal BM dynamics. The wave finite element, WFE, method is then used to decompose the results of a full finite element model of the coupled cochlea into wave components. Results show that apart from the conventional slow wave, other additional types of wave in the passive cochlea do not appear to play a dominant role in normal passive cochlear function.

No description available.

In this thesis the laser ray tracing (LRT) technique for measurement of ocular aberrations has been implemented, validated and applied, in conjunction with complementary techniques, to the study of ocular aberrations in human eyes. In particular, we studied optical aberrations in myopic and hyperopic eyes and the optical changes induced by refractive surgery for myopia and hyperopia. We have studied the impact of the optimisation of some experimental parameters on the estimation of the wave aberration. We demonstrated that although the polarisation state and wavelength of the illumination light affected the intensity patterns of the images obtained using reflectometric aberrometry (LRT and Hartmann Shack sensor), these changes did not affect the estimation of aberrations. We also showed that the difference in the defocus term (focus shift) due to the use of different wavelengths is in agreement with the Longitudinal Chromatic Aberration of the Indiana Chromatic Eye Model for average normal eyes, although intersubject variability is not negligible. In addition, we studied experimentally the influence of the geometrical distribution and density of the pupil sampling on the estimation of aberrations using artificial and normal human eyes, and performed numerical simulations to extend our results to "abnormal"eyes. We found that the spatial distribution of the samples can be more important than the number of samples, for both our measured as well as our simulated "abnormal" eyes. Experimentally, we did not find large differences across patterns except, as expected, for undersampled patterns. We found that hyperopic eyes tended to have more positive asphericity and greater total and corneal spherical aberrati on than myopic eyes, as well as greater 3rd and higher order aberrations. Although we found no significant differences between groups in terms of internal aberrations, internal spherical aberration showed a significant age-related shift toward less negative values in the hyperopic group. We also assessed the impact of the LASIK corneal surgery, a popular surgical technique for correction of refractive errors, on the optical quality for both myopic and hyperopic standard techniques. Third and higher order ocular and an terior corneal aberrations increased with the surgery. Ocular and corneal spherical aberration changed towards more positive values with myopic LASIK, and towards more negative values with hyperopic LASIK. Changes in internal spherical aberration were of opposite sign than those induced in corneal spherical aberration. Changes induced by hyperopic LASIK were larger than those induced by myopic LASIK for a similar attempted correction.

The presence of a bright light source in the visual field, particularly when viewed against a dark background, can generate a form of discomfort, which is often described as ‘discomfort glare’. The mechanisms for discomfort glare remain poorly understood, even after 50 years of multidisciplinary research in this field. The aim of this investigation was to investigate a number of relevant parameters that can affect discomfort glare in order to gain insights into the corresponding mechanisms. We measured retinal illuminance levels for discomfort glare at threshold as a function of source size, eccentricity and surrounding background luminance. In addition, the pupil size was measured throughout and related to the measured thresholds for discomfort glare. A group of 50 subjects with normal visual acuity and no clinical signs of eye disease took part in the primary study that measured discomfort glare thresholds as a function of source size. A light ‘homogenizer’ was used to integrate the concentrated light output from a quad LED light source. Pulse frequency modulation was used to control the intensity of the source and continuous pupil size measurements made it possible to calculate retinal illuminance. Discomfort glare thresholds were estimated by measuring the retinal illuminance of the glare source at threshold using a staircase procedure. Discomfort glare thresholds were measured as a function of glare source area, eccentricity and background luminance. The amplitude of pupil constriction was also measured both below and above the discomfort glare threshold. A model of contrast vision with the filtering of a photoreceptor signal through centre-surround ganglion cells was developed to account for the small size dependence of discomfort glare thresholds that was observed experimentally. Another model for scattered light was applied to compute the corresponding pupil constriction amplitude caused by the integrated photoreceptor signals generated by the glare source both within and outside the stimulus area. The threshold for discomfort glare decreased gradually with glare source size and increased with background luminance and showed little dependence on glare source eccentricity. The effect of forward light scatter in the eye was also investigated and a model was developed to account for the continued increase in pupil response amplitude well above the discomfort glare threshold. The effect of glare source size on discomfort glare thresholds could be predicted by a model involving photoreceptor saturation and edge response. When the scattered light outside the stimulus area was also taken into account, the pupil constriction amplitude increased log-linearly with stimulus retinal illuminance both below and above discomfort glare thresholds. These findings suggest that discomfort glare depended largely on the localised retinal illuminance and could be accounted for by the saturation of photoreceptor signals in the retina. The results and the pupil modeling work also suggest that the pupil response to light flux increments continued well above the discomfort glare threshold, largely as a result of light scattered outside the area of the glare source.