Modelling ocular monochromatic aberrations using schematic eyes with homogeneous optical media

Previous research has indicated that schematic eyes incorporating aspheric surfaces but lacking gradient index are unable to model ocular spherical aberration and peripheral astigmatism simultaneously. This limits their use as wide-angle schematic eyes. This thesis challenges this assumption by investigating the flexibility of schematic eyes comprising aspheric optical surfaces and homogeneous optical media. The full variation of ocular component dimensions found in human eyes was established from the literature. Schematic eye parameter variants were limited to these dimensions. The levels of spherical aberration and peripheral astigmatism modelled by these schematic eyes were compared to the range of measured levels. These were also established from the literature. To simplify comparison of modelled and measured data, single value parameters were introduced; the spherical aberration function (SAF), and peripheral astigmatism function (PAF). Some ocular components variations produced a wide range of aberrations without exceeding the limits of human ocular components. The effect of ocular component variations on coma was also investigated, but no comparison could be made as no empirical data exists. It was demonstrated that by combined manipulation of a number of parameters in the schematic eyes it was possible to model all levels of ocular spherical aberration and peripheral astigmatism. However, the unique parameters of a human eye could not be obtained in this way, as a number of models could be used to produce the same spherical aberration and peripheral astigmatism, while giving very different coma levels. It was concluded that these schematic eyes are flexible enough to model the monochromatic aberrations tested, the absence of gradient index being compensated for by altering the asphericity of one or more surfaces.

Short-term stability in refractive status despite large fluctuations in glucose levels in diabetes mellitus type 1 and 2

Purpose: This work investigates how short-term changes in blood glucose concentration affect the refractive components of the diabetic eye in patients with long-term Type 1 and Type 2 diabetes. Methods: Blood glucose concentration, refractive error components (mean spherical equivalent MSE, J0, J45), central corneal thickness (CCT), anterior chamber depth (ACD), crystalline lens thickness (LT), axial length (AL) and ocular aberrations were monitored at two-hourly intervals over a 12-hour period in: 20 T1DM patients (mean age ± SD) 38±14 years, baseline HbA1c 8.6±1.9%; 21 T2DM patients (mean age ± SD) 56±11 years, HbA1c 7.5±1.8%; and in 20 control subjects (mean age ± SD) 49±23 years, HbA1c 5.5±0.5%. The refractive and biometric results were compared with the corresponding changes in blood glucose concentration. Results: Blood glucose concentration at different times was found to vary significantly within (p<0.0005) and between groups (p<0.0005). However, the refractive error components and ocular aberrations were not found to alter significantly over the day in either the diabetic patients or the control subjects (p>0.05). Minor changes of marginal statistical or optical significance were observed in some biometric parameters. Similarly there were some marginally significant differences between the baseline biometric parameters of well-controlled and poorly-controlled diabetic subjects. Conclusion: This work suggests that normal, short-term fluctuations (of up to about 6 mM/l on a timescale of a few hours) in the blood glucose levels of diabetics are not usually associated with acute changes in refractive error or ocular wavefront aberrations. It is therefore possible that factors other than refractive error fluctuations are sometimes responsible for the transient visual problems often reported by diabetic patients. © 2012 Huntjens et al.

Higher-order aberrations in amblyopia:an analysis of pre- and post-wavefront-guided laser refractive correction

For more than a century it has been known that the eye is not a perfect optical system, but rather a system that suffers from aberrations beyond conventional prescriptive descriptions of defocus and astigmatism. Whereas traditional refraction attempts to describe the error of the eye with only two parameters, namely sphere and cylinder, measurements of wavefront aberrations depict the optical error with many more parameters. What remains questionable is the impact these additional parameters have on visual function. Some authors have argued that higher-order aberrations have a considerable effect on visual function and in certain cases this effect is significant enough to induce amblyopia. This has been referred to as ‘higher-order aberration-associated amblyopia’. In such cases, correction of higher-order aberrations would not restore visual function. Others have reported that patients with binocular asymmetric aberrations display an associated unilateral decrease in visual acuity and, if the decline in acuity results from the aberrations alone, such subjects may have been erroneously diagnosed as amblyopes. In these cases, correction of higher-order aberrations would restore visual function. This refractive entity has been termed ‘aberropia’. In order to investigate these hypotheses, the distribution of higher-order aberrations in strabismic, anisometropic and idiopathic amblyopes, and in a group of visual normals, was analysed both before and after wavefront-guided laser refractive correction. The results show: (i) there is no significant asymmetry in higher-order aberrations between amblyopic and fixing eyes prior to laser refractive treatment; (ii) the mean magnitude of higher-order aberrations is similar within the amblyopic and visually normal populations; (iii) a significant improvement in visual acuity can be realised for adult amblyopic patients utilising wavefront-guided laser refractive surgery and a modest increase in contrast sensitivity was observed for the amblyopic eye of anisometropes following treatment (iv) an overall trend towards increased higher-order aberrations following wavefront-guided laser refractive treatment was observed for both visually normal and amblyopic eyes. In conclusion, while the data do not provide any direct evidence for the concepts of either ‘aberropia’ or ‘higher-order aberration-associated amblyopia’, it is clear that gains in visual acuity and contrast sensitivity may be realised following laser refractive treatment of the amblyopic adult eye. Possible mechanisms by which these gains are realised are discussed.

Operator-induced errors in Hartmann-Shack wavefront sensing:model eye study

Purpose: To evaluate the effects of instrument realignment and angular misalignment during the clinical determination of wavefront aberrations by simulation in model eyes. Setting: Aston Academy of Life Sciences, Aston University, Birmingham, United Kingdom. Methods: Six model eyes were examined with wavefront-aberration-supported cornea ablation (WASCA) (Carl Zeiss Meditec) in 4 sessions of 10 measurements each: sessions 1 and 2, consecutive repeated measures without realignment; session 3, realignment of the instrument between readings; session 4, measurements without realignment but with the model eye shifted 6 degrees angularly. Intersession repeatability and the effects of realignment and misalignment were obtained by comparing the measurements in the various sessions for coma, spherical aberration, and higher-order aberrations (HOAs). Results: The mean differences between the 2 sessions without realignment of the instrument were 0.020 μm ± 0.076 (SD) for Z3 - 1(P = .551), 0.009 ± 0.139 μm for Z3 1(P = .877), 0.004 ± 0.037 μm for Z4 0 (P = .820), and 0.005 ± 0.01 μm for HO root mean square (RMS) (P = .301). Differences between the nonrealigned and realigned instruments were -0.017 ± 0.026 μm for Z3 - 1(P = .159), 0.009 ± 0.028 μm for Z3 1 (P = .475), 0.007 ± 0.014 μm for Z4 0(P = .296), and 0.002 ± 0.007 μm for HO RMS (P = 0.529; differences between centered and misaligned instruments were -0.355 ± 0.149 μm for Z3 - 1 (P = .002), 0.007 ± 0.034 μm for Z3 1(P = .620), -0.005 ± 0.081 μm for Z4 0(P = .885), and 0.012 ± 0.020 μm for HO RMS (P = .195). Realignment increased the standard deviation by a factor of 3 compared with the first session without realignment. Conclusions: Repeatability of the WASCA was excellent in all situations tested. Realignment substantially increased the variance of the measurements. Angular misalignment can result in significant errors, particularly in the determination of coma. These findings are important when assessing highly aberrated eyes during follow-up or before surgery. © 2007 ASCRS and ESCRS.

Clinical evaluation of the Softec HD aberration-free aspheric intraocular lens

Purpose: To compare distance and near visual performance with a zero-aberration aspheric intraocular lens (IOL) (Softec HD, Lenstec, Inc. FL, USA) with that of an otherwise identical, but spherical IOL (Softec 1). Setting: Department of Ophthalmology, Solihull Hospital, West Midlands, United Kingdom. Methods: This prospective study comprised 37 patients with a Softec 1 spherical IOL implanted in one eye, who underwent phacoemulsification and received the Softec HD aspheric IOL in the fellow eye. One month post-operatively, unaided distance and near vision, residual refraction, best spectacle corrected distance and near visual acuity, reading speed, pseudoaccommodation and photopic contrast sensitivity were recorded. Wavefront analysis enabled comparison of higher order aberrations between the IOLs. Results: Prior to surgery, the Softec 1 and Softec HD eyes were not significantly different. Post-operatively, unaided vision, best spectacle corrected visual acuity and residual refraction were not significantly different between the eyes, nor were there significant differences observed between the measured wavefront aberrations. Once implanted, the range of focus was significantly better in the Softec HD IOL eye than the Softec 1 IOL eye and, although reading speed was equivalent to the Softec 1 eye, the print size at which this could be achieved was significantly smaller. Conclusions: Depth of field was significantly improved with the aspheric IOL compared with the spherical IOL, without any compromise in distance visual performance between the two IOLs.

Optical imaging of retina in response to grating stimuli in cats

We examined the intrinsic signals in response to grating stimuli in order to determine whether the light-evoked intrinsic signals of the retina are due to changes in the photoreceptor activities induced by the image projected on to the retina or are due to neural activities of the inner retina. The retinas of the left eye of 12 cats under general anesthesia were examined by a functional imaging fundus camera. Near infrared light was used to monitor the reflectance changes (RCs) of the retina. Vertical grating were used to stimulate the retina at 4 Hz. The spatial frequencies of the gratings were 0.05, 0.11, 0.22, 0.43, 0.86, 1.73, and 3.46 cycles/degree (cpd). Ten images were averaged and used to analyze the RCs to obtain the peak value (PV) of a two dimensional fast Fourier transfer of the RCs. The wavefront aberrations (WA) were measured with a compact wavefront aberrometer and the spatial modulation transfer function (MTF) of the eye was calculated. The retinal reflectance image had a grating pattern. The PV of the spatial sensitivity curve was highest at low spatial frequencies (0.05 and 0.11 cpd), and the sensitivity decreased steeply with an increase in the spatial frequency. RCs were not detectable at 3.46 cpd. The MTF decreased gradually with increases in the spatial frequencies and was 0.68 at 3.46 cpd. The reflectance pattern of the retinal intrinsic signal elicited by grating stimuli of different spatial frequencies was different from that of the MTF. This suggests that the intrinsic signal represents not only the response of the photoreceptors but also other neuronal or vascular changes in the retina.

Accommodative response to electrical stimulation of the sclera of peripheral cornea in cats and porcines

Purpose: We have reported that the changes in the accommodative response to electrical stimulation of the branches of the ciliary nerves in cats. (Miyagawa et al, PLoS One, 2014). We have also reported that no robust accommodative responses to the electrical stimulations of the sclera of peripheral cornea (SSPC) were observed in enucleated porcine eyes (Mihashi et al, VPOptics, 2014). In this study, accommodative responses to SSPC stimulation in cats and porcines were investigated. Methods: Two eyes of two cats under anesthesia and after they were sacrificed were studied. Three enucleated porcine eyes obtained from a local slaughterhouse were also studied. Trains of biphasic pulses (current, 3 mA; duration, 2 ms/phase; frequency, 40 Hz) were applied using a tungsten electrode (0.3mm diameter) from several orientations. Wavefront sensing with a compact wavefront aberrometer (Uday et al J Cataract Refract Surg, 2013) were performed before and 4 s (cat) and 10 s (pig) after the stimulations and wavefront aberrations including spherical errors were analyzed over a 4-mm pupil area. Results: In the first cat under anesthesia, at three out of seven stimulus positions, 0.2 D hyperopic accommodative responses were observed and in two orientations, myopic responses were observed. For the other cat, weak accommodative responses including astigmatic changes were observed. In the sacrificed condition of the second cat, 0.1 D myopic response was observed for one stimulus orientation and the smaller responses were observed at six out of eight stimulus positions. No accommodative responses were elicited for the enucleated porcine eyes. Conclusions: In the anesthetized cats, electrical stimulation of the SSPC induced accommodative responses; the responses were unstable and weaker than the responses by the ciliary nerve stimulations we observed in our previous study. Small accommodative responses were observed after one of two cats had been sacrificed, but no accommodative responses were detected in the enucleated porcine eyes. Further studies are needed to confirm difference in the accommodation functions in the two species.

A preliminary investigation into the effects of ocular lubricants on higher order aberrations in normal and dry eye subjects

Purpose: To study the effects of ocular lubricants on higher order aberrations in normal and self-diagnosed dry eyes. Methods: Unpreserved hypromellose drops, Tears Again™ liposome spray and a combination of both were administered to the right eye of 24 normal and 24 dry eye subjects following classification according to a 5 point questionnaire. Total ocular higher order aberrations, coma, spherical aberration and Strehl ratios for higher order aberrations were measured using the Nidek OPD-Scan III (Nidek Technologies, Gamagori, Japan) at baseline, immediately after application and after 60. min. The aberration data were analyzed over a 5. mm natural pupil using Zernike polynomials. Each intervention was assessed on a separate day and comfort levels were recorded before and after application. Corneal staining was assessed and product preference recorded after the final measurement for each intervention. Results: Hypromellose drops caused an increase in total higher order aberrations (p= <0.01 in normal and dry eyes) and a reduction in Strehl ratio (normal eyes: p= <0.01, dry eyes p= 0.01) immediately after instillation. There were no significant differences between normal and self-diagnosed dry eyes for response to intervention and no improvement in visual quality or reduction in higher order aberrations after 60. min. Differences in comfort levels failed to reach statistical significance. Conclusion: Combining treatments does not offer any benefit over individual treatments in self-diagnosed dry eyes and no individual intervention reached statistical significance. Symptomatic subjects with dry eye and no corneal staining reported an improvement in comfort after using lubricants. © 2013 British Contact Lens Association.

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.

Nidek OPD-scan analysis of normal, keratoconic, and penetrating keratoplasty eyes

PURPOSE: To determine by wavefront analysis the difference between eyes considered normal, eyes diagnosed with keratoconus, and eyes that have undergone penetrating keratoplasty METHODS: The Nidek OPD-Scan wavefront aberrometer was used to measure ocular aberrations out to the sixth Zernike order. One hundred and thirty eyes that were free of ocular pathology, 41 eyes diagnosed with keratoconus, and 8 eyes that had undergone penetrating keratoplasty were compared for differences in root mean square value. Three and five millimeter root mean square values of the refractive power aberrometry maps of the three classes of eyes were compared. Radially symmetric and irregular higher order aberration values were compared for differences in magnitude. RESULTS: Root mean square values were lower in eyes free of ocular pathology compared to eyes with keratoconus and eyes that had undergone penetrating keratoplasty. The aberrations were larger with the 5-mm pupil. Coma and spherical aberration values were lower in normal eyes. CONCLUSION: Wavefront aberrometry of normal, pathological, and eyes after surgery may help to explain the visual distortions encountered by patients. The ability to measure highly aberrated eyes allows an objective assessment of the optical consequences of ocular pathology and surgery. The Nidek OPD-Scan can be used in areas other than refractive surgery.

Repeatability of ocular aberration measurements in patients with keratoconus

Purpose: To explore the repeatability of lower-order and higher-order ocular aberrations measured in patients with keratoconus. Methods: The IRX-3 (Imagine Eyes, Paris, France) aberrometer was used to record lower-order and higher-order aberrations in 31 eyes of 31 patients with keratoconus. Four monocular measurements were taken consecutively for each patient. The aberrometry data were analysed up to the 5th Zernike order for a 4-mm pupil diameter. The data were evaluated using repeated-measures anova and Friedman analyses. Repeatability was analysed using within-subject standard deviation (SW) and the repeatability limit (r) calculated as 1.96 ×√2×Sw. Results: Of the 11 aberration terms evaluated, the repeatability of Z (2,0) (mean= 1.36μm; SW=0.09μm; r=0.26μm); Z (2,±2) RMS (mean=1.05μm; SW= 0.09μm; r=0.24μm) and Z (4,0) aberrations (mean=0.34μm; SW=0.09 μm; r=0.24μm) showed the highest variability. In contrast, Z (3,±1) RMS aberrations (mean=0.85μm; SW=0.06μm; r=0.16μm) and Z (4,±2) RMS aberrations (mean=0.40μm; SW=0.07μm; r=0.18μm) showed comparatively better repeatability. Conclusions: The lower-order and higher-order aberrations measured in this group of keratoconic patients showed higher levels of variability compared to previous investigations of visually-normal subjects. These results may be of interest to eyecare practitioners involved in the design and fitting of aberration-controlling contact lenses for patients with keratoconus. © 2011 The College of Optometrists.

Eye infections caused by fungi (ocular mycoses)

Ocular mycoses are being reported with increasing frequency as a consequence of new medical practice and an increase in the number of immunosuppressed patients in the population, e.g.,, patients who are HIV positive and patients receiving radiation or chemotherapy. This article describes the ocular mycoses likely to be seen in such patients.

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.

Accommodating intraocular lenses:a review of design concepts, usage and assessment methods

The correction of presbyopia and restoration of true accommodative function to the ageing eye is the focus of much ongoing research and clinical work. A range of accommodating intraocular lenses (AIOLs) implanted during cataract surgery has been developed and they are designed to change either their position or shape in response to ciliary muscle contraction to generate an increase in dioptric power. Two main design concepts exist. First, axial shift concepts rely on anterior axial movement of one or two optics creating accommodative ability. Second, curvature change designs are designed to provide significant amplitudes of accommodation with little physical displacement. Single-optic devices have been used most widely, although the true accommodative ability provided by forward shift of the optic appears limited and recent findings indicate that alternative factors such as flexing of the optic to alter ocular aberrations may be responsible for the enhanced near vision reported in published studies. Techniques for analysing the performance of AIOLs have not been standardised and clinical studies have reported findings using a wide range of both subjective and objective methods, making it difficult to gauge the success of these implants. There is a need for longitudinal studies using objective methods to assess long-term performance of AIOLs and to determine if true accommodation is restored by the designs available. While dual-optic and curvature change IOLs are designed to provide greater amplitudes of accommodation than is possible with single-optic devices, several of these implants are in the early stages of development and require significant further work before human use is possible. A number of challenges remain and must be addressed before the ultimate goal of restoring youthful levels of accommodation to the presbyopic eye can be achieved.

Treatment of ocular allergies:nonpharmacologic, pharmacologic and immunotherapy

Ocular allergy is a significant and growing issue worldwide but for many patients, it is often not differentiated from systemic conditions, such as hay fever. Management of seasonal and perennial allergic conjunctivitis is often poor. Management is principally through avoidance measures (blocking or hygiene), nonpharmaceutical (such as artificial tears and cold compresses) and pharmaceutical (such as topical antihistamines and prophylactic mast cell stabilizers). Vernal and atopic keratoconjunctivitis are more severe and generally need treatment with NSAIDs, steroids and immunomodulators. Giant papillary conjunctivitis can be related to allergy but also is often contact lens related and in such cases can be managed by a period of abstinence and replacement of the lens or a change in lens material and/or design. Immunotherapy can be efficacious in severe, persistent cases of contact lens or allergic conjunctivitis.