Ocular biomaterials and the anterior eye

Hydrogels, water swollen polymer matrices, have been utilised in many biomedical applications, as there is the potential to manipulate the properties for a given application by changing the chemical structure of the constituent monomers The eye provides an excellent site to examne the interaction between a synthetic material and a complex biological fluid without invasive surgery. There is a need for the development of new synthetic hydrogels for use in the anterior eye, Three applications of hydrogels in the eye were considered in this thesis. For some patients, the only hope of any visual improvement lies in the use of an artificial cornea, or keratoprosthesis, Preliminary investigations of a series of simple homogeneous hydrogel copolymers revealed that the mechanical properties required to withstand surgery and in eye stresses, were not achieved This lead to work on the development of semi-interpenetrating polymer networks based on the aforementioned copolymers, Manufacture of the device and cell response were also studied. Lasers have been employed in ocular surgery to correct refractive defects. If an irregular surface is ablated, an irregular surface is obtained. A hydrogel system was investigated that could be applied to the eye prior to ablation to create a smooth surface. Factors that may influence ablation rate were explored, Soft contact lenses can be used as a probe to study the interaction between synthetic materials and the biological constituents of tears. This has lead to the development of many sensitive analytical techniques for protein and lipid deposition, one of which is fluorescence spectrophotometry. Various commercially available soft contact lenses were worn for different periods of time and then analysed for protein and lipid deposition using fluorescence spectrophotometry, The influence of water content, degree of ionicity and the lens material on the level and type of deposition was investigated.

Alzheimer’s disease and the eye

Dementia, including Alzheimer’s disease (AD), is a major disorder causing visual problems in the elderly population. The pathology of AD includes the deposition in the brain of abnormal aggregates of ß-amyloid (Aß) in the form of senile plaques (SP) and abnormally phosphorylated tau in the form of neurofibrillary tangles (NFT). A variety of visual problems have been reported in patients with AD including loss of visual acuity (VA), colour vision and visual fields; changes in pupillary response to mydriatics, defects in fixation and in smooth and saccadic eye movements; changes in contrast sensitivity and in visual evoked potentials (VEP); and disturbances of complex visual functions such as reading, visuospatial function, and in the naming and identification of objects. Many of these changes are controversial with conflicting data in the literature and no ocular or visual feature can be regarded as particularly diagnostic of AD. In addition, some pathological changes have been observed to affect the eye, visual pathway, and visual cortex in AD. The optometrist has a role in helping a patient with AD, if it is believed that signs and symptoms of the disease are present, so as to optimize visual function and improve the quality of life. (J Optom 2009;2:103-111 ©2009 Spanish Council of Optometry)

Creutzfeldt-Jakob disease and the eye

This article describes: 1) the symptoms and pathology of CJD, 2) how prion proteins may cause CJD, 3) the visual signs and symptoms of CJD, and 4) the scientific evidence which supports a possible transmission of CJD via optometric devices.

Transversal and longitudinal images from the retina of the living eye using low coherence interferometry

An optical coherence tomography (OCT) system to produce both longitudinal and transversal images of the in vivo human eye is presented. For the first time, OCT transversal images collected from the living eye at 50-µm depth steps show details unobtainable with the state-of-the-art scanning laser ophthalmoscope. Images of up to 3×3?mm are produced from the retina in less than a second. For images larger than 1.6×1.6?mm, a path modulation is introduced by the galvanometric scanning mirror and is used as an effective phase modulation method.

Fiberised set-up for eye length measurement

We describe a configuration consisting of two fiberised Michelson interferometers and show that, with an optical balanced technique and suitable electronics, the signal corresponding to coherent interference in the first interferometer can be sufficiently attenuated in the channel processing the signal from the second interferometer. In this way it is possible to display simultaneous reflectograms of two different regions in the eye (e.g. cornea and retina) and infer the eye length from these measurements.

Some clinical aspects of the eye in extended contact lens wear

The limbal vascular response to extended contact lens wear was examined in a group comparative study initially intended to last eighteen months. After six months all patients wearing contact lenses had presented with micro-epithelial cysts. This unanticipated occurrence of the micro-epithelial-cysts necessitated termination of the study, and limited the quantity of data collected. However, sufficient results were available to allow a limited description of •the vascular response to this form of contact lens wear. Interpretations of the date collected ore discussed in relation to suggested vasostimulating factors in the cornea. The micro-epithelial cysts observed after extended wear were classified and their rate of recovery recorded. A further clinical study was undertaken to observe cysts in both contact lens - and non contact lens-wearing eyes. Cysts were observed in every category of patient, although the characteristic patterns varied. These observations of micro-epithelial cysts are discussed with respect to the aetiopathogeneses of corneal epithelial cystic disorders. Subsequently, attempts were made to induce cysts in rabbit corneae by extended contact lens wear. Clinical observations revealed cyst-like appearances. Histological sections did not contain cysts but did exhibit signs characteristic •of cystic disorders of the corneal epithelium. In general, the results from the study indicate that extended wear is subjectively acceptable to contact lens wearers. However, the objective findings of significant vascular changes, micro-epithelial cysts and cases of acute red eye response cast considerable doubt on the recommendation of extended wear contact lenses for purely cosmetic applications.

Visual performance of the human eye with soft hydrophilic contact lenses

The recording of visual acuity using the Snellen letter chart is only a limited measure of the visual performance of an eye wearing a refractive aid. Qualitative in addition to quantitative information is required to establish such a parameter: spatial, temporal and photometric aspects must all be incorporated into the test procedure. The literature relating to the correction of ametropia by refractive aids was reviewed. Selected aspects of a comparison between the correction provided by spectacles and contact lenses were considered. Special attention was directed to soft hydrophilic contact lenses. Despite technological advances which have produced physiologically acceptable soft lenses, there still remain associated with this recent form of refractive aid unpredictable visual factors. Several techniques for vision assessment were described, and previous studies of visual performance were discussed. To facilitate the investigation of visual performance in a clinical environment, a new semi-automated system was described: this utilized the presentation of broken ring test stimuli on a television screen. The research project comprised two stages. Initial work was concerned with the validation of the television system, including the optimization of its several operational variables. The second phase involved the utilization of the system in an investigation of visual performance aspects of the first month of regular daily soft contact lens wear by experimentally-naive subjects. On the basis of the results of this work an ‘homoeostatic’ model has been proposed to represent the strategy which an observer adopts in order to optimize his visual performance with soft contact lenses.

The investigation of the sensitivity gradient of the visual field, as a function of stimulus dynamic range, in the normal and abnormal eye

The study utilized the advanced technology provided by automated perimeters to investigate the hypothesis that patients with retinitis pigmentosa behave atypically over the dynamic range and to concurrently determine the influence of extraneous factors on the format of the normal perimetric sensitivity profile. The perimetric processing of some patients with retinitis pigmentosa was considered to be abnormal in either the temporal and/or the spatial domain. The standard size III stimulus saturated the central regions and was thus ineffective in detecting early depressions in sensitivity in these areas. When stimulus size was scaled in inverse proportion to the square root of ganglion cell receptive field density (M-scaled), isosensitive profiles did not result, although cortical representation was theoretically equivalent across the visual field. It was conjectured that this was due to variations in the ganglion cell characteristics with increasing peripheral angle, most notably spatial summation. It was concluded that the development of perimetric routines incorporating stimulus sizes adjusted in proportion to the coverage factor of retinal ganglion cells would enhance the diagnostic capacity of perimetry. Good general and local correspondence was found between perimetric sensitivity and the available retinal cell counts. Intraocular light scatter arising both from simulations and media opacities depressed perimetric sensitivity. Attenuation was greater centrally for the smaller LED stimuli, whereas the reverse was true for the larger projected stimuli. Prior perimetric experience and pupil size also demonstrated eccentricity-dependent effect on sensitivity. Practice improved perimetric sensitivity for projected stimuli at eccentricities greater than or equal to 30o; particularly in the superior region. Increase in pupil size for LED stimuli enhanced sensitivity at eccentricities greater than 10o. Conversely, microfluctuation in the accommodative response during perimetric examination and the correction of peripheral refractive error had no significant influence on perimetric sensitivity.

Investigation of chromatic function in the normal and abnormal eye

This study examined the use of non-standard parameters to investigate the visual field, with particular reference to the detection of glaucomatous visual field loss. Evaluation of the new perimetric strategy for threshold estimation - FASTPAC, demonstrated a reduction in the examination time of normals compared to the standard strategy. Despite an increased within-test variability the FASTPAC strategy produced a similar mean sensitivity to the standard strategy, reducing the effects of patient fatigue. The new technique of Blue-Yellow perimetry was compared to White-White perimetry for the detection of glaucomatous field loss in OHT and POAG. Using a database of normal subjects, confidence limits for normality were constructed to account for the increased between-subject variability with increase in age and eccentricity and for the greater variability of the Blue-Yellow field compared to the White-White field. Effects of individual ocular media absorption had little effect on Blue-Yellow field variability. Total and pattern probability analysis revealed five of 27 OHTs to exhibit Blue-Yellow focal abnormalities; two of these patients subsequently developed White-White loss. Twelve of the 24 POAGs revealed wider and/or deeper Blue-Yellow loss compared with the White-White field. Blue-Yellow perimetry showed good sensitivity and specificity characteristics, however, lack of perimetric experience and the presence of cataract influenced the Blue-Yellow visual field and may confound the interpretation of Blue-Yellow visual field loss. Visual field indices demonstrated a moderate relationship to the structural parameters of the optic nerve head using scanning laser tomography. No abnormalities in Blue-Yellow or Red-Green colour CS was apparent for the OHT patients. A greater vulnerability of the SWS pathway in glaucoma was demonstrated using Blue-Yellow perimetry however predicting which patients may benefit from B-Y perimetric examination is difficult. Furthermore, cataract and the extent of the field loss may limit the extent to which the integrity of the SWS channels can be selectively examined.

Optimising the clinical analysis of retinal image quality in the human eye

Visual perception is dependent on both light transmission through the eye and neuronal conduction through the visual pathway. Advances in clinical diagnostics and treatment modalities over recent years have increased the opportunities to improve the optical path and retinal image quality. Higher order aberrations and retinal straylight are two major factors that influence light transmission through the eye and ultimately, visual outcome. Recent technological advancements have brought these important factors into the clinical domain, however the potential applications of these tools and considerations regarding interpretation of data are much underestimated. The purpose of this thesis was to validate and optimise wavefront analysers and a new clinical tool for the objective evaluation of intraocular scatter. The application of these methods in a clinical setting involving a range of conditions was also explored. The work was divided into two principal sections: 1. Wavefront Aberrometry: optimisation, validation and clinical application The main findings of this work were: • Observer manipulation of the aberrometer increases variability by a factor of 3. • Ocular misalignment can profoundly affect reliability, notably for off-axis aberrations. • Aberrations measured with wavefront analysers using different principles are not interchangeable, with poor relationships and significant differences between values. • Instrument myopia of around 0.30D is induced when performing wavefront analysis in non-cyclopleged eyes; values can be as high as 3D, being higher as the baseline level of myopia decreases. Associated accommodation changes may result in relevant changes to the aberration profile, particularly with respect to spherical aberration. • Young adult healthy Caucasian eyes have significantly more spherical aberration than Asian eyes when matched for age, gender, axial length and refractive error. Axial length is significantly correlated with most components of the aberration profile. 2. Intraocular light scatter: Evaluation of subjective measures and validation and application of a new objective method utilising clinically derived wavefront patterns. The main findings of this work were: • Subjective measures of clinical straylight are highly repeatable. Three measurements are suggested as the optimum number for increased reliability. • Significant differences in straylight values were found for contact lenses designed for contrast enhancement compared to clear lenses of the same design and material specifications. Specifically, grey/green tints induced significantly higher values of retinal straylight. • Wavefront patterns from a commercial Hartmann-Shack device can be used to obtain objective measures of scatter and are well correlated with subjective straylight values. • Perceived retinal stray light was similar in groups of patients implanted with monofocal and multi focal intraocular lenses. Correlation between objective and subjective measurements of scatter is poor, possibly due to different illumination conditions between the testing procedures, or a neural component which may alter with age. Careful acquisition results in highly reproducible in vivo measures of higher order aberrations; however, data from different devices are not interchangeable which brings the accuracy of measurement into question. Objective measures of intraocular straylight can be derived from clinical aberrometry and may be of great diagnostic and management importance in the future.

Screening for eye disease in the elderly:is it worth it?

Should we be screening for eye disorders in the elderly population? Visual impairment in the elderly can be associated with reduced functional status and quality of life, low social contact, depression, and falls and hip fractures (Dargent-Molina et al, 1996). It therefore would seem sensible to identify those elderly patients who have or are at risk of developing sight-threatening eye disorders, and offer them treatment. However, screening for disease of any kind raises a number of issues.

Proliferative diabetic retinopathy (R3) referrals from the digital diabetic retinopathy screening program:urgency of appointment in the hospital eye service achieved and needed?

DESIGN. Retrospective analysis PURPOSE. To assess the clinical characteristics and outcomes of patients identified with proliferative diabetic retinopathy (PDR) referred from the screening program to the hospital eye services (HES) METHODS. a retrospective analysis of urgently referred PDR cases to Birmingham Heartlands HES from august 2008 until July 2010 RESULTS. 130 urgent diabetic retinopathy referrals were made and reviewed. 103 (68% male, 80% type 2 diabetes) were referred for PDR with a mean age of 59 years, mean diabetes duration of 17.8years. 69% were on insulin treatment at the time of the screening, with mean HbA1c of 10.4% (range-5.7 to 16.5%). 65% of the patients were offered appointments at HES within two weeks after referral from the screening. 50.5% of the patients were seen in the HES within 2 weeks, 22 and 16 % were seen 2-4 and 4-8 weeks after referral respectively. 6 patients never attended ophthalmology examination during the two years of review. Of all the attendees, 56% were booked for pan retinal photocoagulation (PRP) & 9(9.3%) for macular laser respectively on their 1st HES visit. 75% of the patients were newly diagnosed PDR and 26 had previous PRP laser but lost to follow up. 63 patients ( 66%) received either PRP or macular laser treatment (85.7% of which is PRP). 63% of the PRP treatment was performed within a month of first HES attendance. Retinopathy grading discrepancy between the screening program and HES was noted in 20% (21 patients). CONCLUSIONS. This data suggests that the digital screening programme is appropriately identifying high risk patients with PDR with timely PRP laser treatment in the majority of patients but raises concern over patients lost to follow up (hence failsafe tracking of appointment attendance), and review of grading discrepancies between the ophthalmology and screening service.

Evaluation of dry eye

Dry eye is a common yet complex condition. Intrinsic and extrinsic factors can cause dysfunction of the lids, lacrimal glands, meibomian glands, ocular surface cells, or neural network. These problems would ultimately be expressed at the tear film-ocular surface interface. The manifestations of these problems are experienced as symptoms such as grittiness, discomfort, burning sensation, hyperemia, and secondary epiphora in some cases. Accurate investigation of dry eye is crucial to correct management of the condition. Techniques can be classed according to their investigation of tear production, tear stability, and surface damage (including histological tests). The application, validity, reliability, compatibility, protocols, and indications for these are important. The use of a diagnostic algorithm may lead to more accurate diagnosis and management. The lack of correlation between signs and symptoms seems to favor tear film osmolarity, an objective biomarker, as the best current clue to correct diagnosis.

New strategy to overcome the intrinsic difficulty of phospholipids solubilisation and delivery to the eye

Purpose: Lipids play a vital role at interfaces such as the tear film in the protection of the anterior eye. Their role is to act as lubricants and reduce surface and interfacial tension. Although there is a lack of appropriate methods to solubilize and dilute phospholipids to the tear film. Here, we report that styrene-maleic acid copolymers (PSMA), can form polymer–lipid complexes in the form of monodisperse nanometric particles, which can easily solubilise these phospholipid molecules by avoiding for example, the use of any kind of surfactant. Method: The interactions of PSMA with phospholipids have been studied by its adsorption from aqueous solutions into monolayers of dimyristoyl-phosphorylcholine (DMPC). The Langmuir trough (LT) technique is used to study this pH-dependant complex formation. The formed nanoparticles have been also analysed by 31P NMR, particle size distribution by light scattering (DLS) and morphology by electron microscopy (SEM). Results: The LT has been found to be a useful technique for in vitro simulation of in vivo lipid layer behaviour: The limiting surface pressure of unstable tear films ranges between 20 and 30 mN/m. More stable tear films show an increase in surface pressure, within the range of 35–45 mN/m. The DMPC monolayers have a limiting surface pressure of 38 mN/m (water), and 45 mN/m (pH 4 buffer), and the PSMA-DMPC complexes formed at pH 4 have a value of 42 mN/m, which resembles that of the stable tear film. The average particle size distribution is 53 ± 10 nm with a low polydispersity index (PDI) of 0.24 ± 0.03. Conclusions: New biocompatible and cheap lipid solubilising agents such as PSMA can be used for the study of the tear film composition and properties. These polymer–lipid complexes in the form of nanoparticles can be used to solubilise and release in a controlled way other hydrophobic molecules such as some drugs or proteins.

In-Motes EYE:a real time application for automobiles in wireless sensor networks

Wireless sensor networks have been identified as one of the key technologies for the 21st century. In order to overcome their limitations such as fault tolerance and conservation of energy, we propose a middleware solution, In-Motes. In-Motes stands as a fault tolerant platform for deploying and monitoring applications in real time offers a number of possibilities for the end user giving him in parallel the freedom to experiment with various parameters, in an effort the deployed applications to run in an energy efficient manner inside the network. The proposed scheme is evaluated through the In-Motes EYE application, aiming to test its merits under real time conditions. In-Motes EYE application which is an agent based real time In-Motes application developed for sensing acceleration variations in an environment. The application was tested in a prototype area, road alike, for a period of four months.