Diurnal variations in ocular aberrations of human eyes

Purpose: To investigate the diurnal variations in ocular wavefront aberrations over two consecutive days in young adult subjects. Materials and methods: Measurements of both lower-order (sphero-cylindrical refractive powers) and higher-order (3rd and 4th order aberration terms) ocular aberrations were collected for 30 young adult subjects at ten different times over two consecutive days using a Hartmann-Shack aberrometer. Fifteen subjects were myopic and 15 were emmetropic. Five sets of measurements were collected each day at approximately 3 hourly intervals, with the first measurement taken at ~9 am and the final measurement at ~9 pm. Results: Spherical equivalent refraction (p = 0.029) and spherical aberration (p = 0.043) were both found to undergo significant diurnal variation over the two measurement days. The spherical equivalent was typically found to be at a maximum (i.e. most hyperopic) at the morning measurement, with a small myopic shift of 0.37 ± 0.15 D observed over the course of the day. The mean spherical aberration of all subjects (0.038 ± 0.048 μm) was found to be positive during the day and gradually became more negative into the evening, with a mean amplitude of change of 0.036 ± 0.02 μm. None of the other considered sphero-cylindrical refractive power components or higher-order aberrations exhibited significant diurnal variation over the two days of the experiment (p>0.05). Except for the lower-order astigmatism at 90/180 deg (p = 0.040), there were no significant differences between myopes and emmetropes in the magnitude and timing of the observed diurnal variations (p>0.05). Conclusions: Significant diurnal variations in spherical equivalent and spherical aberration were consistently observed over two consecutive days of measurement. Research and clinical applications requiring precise refractive error and wavefront measurements should take these diurnal changes into account when interpreting wavefront data.

Changes in ocular biometrics and refraction during near work in downward gaze over time

PURPOSE To investigate changes in the characteristics of the corneal optics, total optics, anterior biometrics and axial length of the eye during a near task, in downward gaze, over 10 min. METHODS Ten emmetropes (mean - 0.14 ± 0.24 DS) and 10 myopes (mean - 2.26 ± 1.42 DS) aged from 18 to 30 years were recruited. To measure ocular biometrics and corneal topography in downward gaze, an optical biometer (Lenstar LS900) and a rotating Scheimpflug camera (Pentacam HR) were inclined on a custom built, height and tilt adjustable table. The total optics of the eye were measured in downward gaze with binocular fixation using a modified Shack-Hartmann wavefront sensor. Initially, subjects performed a distance viewing task at primary gaze for 10 min to provide a "wash-out" period for prior visual tasks. A distance task (watching video at 6 m) in downward gaze (25°) and a near task (watching video on a portable LCD screen with 2.5 D accommodation demand) in primary gaze and 25°downward gaze were then carried out, each for 10 min in a randomized order. During measurements, in dichoptic view, a Maltese cross was fixated with the right (untested) eye and the instrument’s fixation target was fixated with the subject’s tested left eye. Immediately after (0 min), 5 and 10 min from the commencement of each trial, measurements of ocular parameters were acquired in downward gaze. RESULTS Axial length exhibited a significant increase with downward gaze and accommodation over time (p<0.05). The greatest axial elongation was observed in downward gaze with 2.5 D accommodation after 10 min (mean change from baseline 23±3 µm). Downward gaze also caused greater changes in anterior chamber depth (ACD) and lens thickness (LT) with accommodation (ACD mean change -163±12µm at 10 min; LT mean change 173±17 µm at 10 min) compared to primary gaze with accommodation (ACD mean change -138±12µm at 10 min; LT mean change 131±15 µm at 10 min). Both corneal power and total ocular power changed by a small but significant amount with downward gaze (p<0.05), resulting in a myopic shift (~0.10 D) in the spherical power of the eye compared with primary gaze. CONCLUSION The axial length, anterior biometrics and ocular refraction change significantly with accommodation in downward gaze as a function of time. These findings provide new insights into the optical and bio-mechanical changes of the eye during typical near tasks.

Myopic anisometropia : ocular characteristics and aetiological considerations

Anisometropia represents a unique example of ocular development, where the two eyes of an individual, with an identical genetic background and seemingly subject to identical environmental influences, can grow asymmetrically to produce significantly different refractive errors. This review provides an overview of the research examining myopic anisometropia, the ocular characteristics underlying the condition and the potential aetiological factors involved. Various mechanical factors are discussed, including corneal structure, intraocular pressure and forces generated during near work that may contribute to development of anisomyopia. Potential visually guided mechanisms of unequal ocular growth are also explored, including the influence of astigmatism, accommodation, higher-order aberrations and the choroidal response to altered visual experience. The association between binocular vision, ocular dominance and asymmetric refraction is also considered, along with a review of the genetic contribution to the aetiology of myopic anisometropia. Despite a significant amount of research into the biomechanical, structural and optical characteristics of anisometropic eyes, there is still no unifying theory, which adequately explains how two eyes within the same visual system grow to different endpoints.

Effects of pupil center shift on ocular aberrations

Purpose: To investigate effects of pupil shifts, occurring with changes in luminance and accommodation stimuli, on refraction components and higher-order aberrations. Method: Participants were young and older groups (n=20, 22±2 years, age range 18–25 years; n=19, 49±4 years, 45–58 years). Aberrations/refractions at 4 mm and 3 mm diameters were compared between centered and decentered pupils for low (background 0.01cd/m², 0D), and high (6100cd/m², 4D or 6D) stimuli. Decentration was the difference between pupil centers for low and high stimuli. Clinical important changes with decentration were: M ±0.50D or ±0.25D, J180 and J45 ±0.25D or ±0.125D, HORMS ±0.05m, C(3, 1) ±0.05m, C(4, 0) ±0.05m. Results: Because of small pupil shifts in most participants (mean 0.26mm), there were few important changes in most refraction components and higher-order aberration terms. However, M changed by >0.25 D for a third of participants with 4mm pupils. When determining refractions from 2nd-6th order aberration coefficients, the more stringent criteria gave 76/ 534 (14%) possible important changes. Some participants had large pupil shifts with considerable aberration changes. Comparisons at the high stimulus were possible for only 11 participants because of small pupils. When refractions were determined from 2nd order aberration coefficients only, there were only 35 (7%) important changes for the more stringent criteria. Conclusion: Usually pupil shifts with changes in stimulus conditions have little influence on aberrations, but they can with high shifts. The number of aberrations orders that are considered as contributing to refraction influences the proportion of cases that might be considered clinically important.

Comparison of ocular modulation transfer function determined by a ray-tracing aberrometer and a double-pass system in early cataract patients

BACKGROUND: The evaluation of retinal image quality in cataract eyes has gained importance and the clinical modulation transfer functions (MTF) can obtained by aberrometer and double pass (DP) system. This study aimed to compare MTF derived from a ray tracing aberrometer and a DP system in early cataractous and normal eyes. METHODS: There were 128 subjects with 61 control eyes and 67 eyes with early cataract defined according to the Lens Opacities Classification System III. A laser ray-tracing wavefront aberrometer (iTrace) and a double pass (DP) system (OQAS) assessed ocular MTF for 6.0 mm pupil diameters following dilation. Areas under the MTF (AUMTF) and their correlations were analyzed. Stepwise multiple regression analysis assessed factors affecting the differences between iTrace- and OQAS-derived AUMTF for the early cataract group. RESULTS: For both early cataract and control groups, iTrace-derived MTFs were higher than OQAS-derived MTFs across a range of spatial frequencies (P < 0.01). No significant difference between the two groups occurred for iTrace-derived AUMTF, but the early cataract group had significantly smaller OQAS-derived AUMTF than did the control group (P < 0.01). AUMTF determined from both the techniques demonstrated significant correlations with nuclear opacities, higher-order aberrations (HOAs), visual acuity, and contrast sensitivity functions, while the OQAS-derived AUMTF also demonstrated significant correlations with age and cortical opacity grade. The factors significantly affecting the difference between iTrace and OQAS AUMTF were root-mean-squared HOAs (standardized beta coefficient = -0.63, P < 0.01) and age (standardized beta coefficient = 0.26, P < 0.01). CONCLUSIONS: MTFs determined from a iTrace and a DP system (OQAS) differ significantly in early cataractous and normal subjects. Correlations with visual performance were higher for the DP system. OQAS-derived MTF may be useful as an indicator of visual performance in early cataract eyes.

Eye rubbing-induced changes in intraocular pressure and corneal thickness measured at five locations, in subjects with ocular allergy

AIM To assess the effects of eye rubbing on corneal thickness (CT) and intraocular pressure (IOP) measurements obtained 0-30min after habitual eye rubbing in symptomatic patients. METHODS Measurements of IOP and CT were obtained at five locations (central, temporal, superior, nasal and inferior) before, and every 5min for 30min interval after 30s of eye rubbing, for 25 randomly selected eyes of 14 subjects with ocular allergy and 11 age-matched normals. Differences in measurements were calculated in each group [Baseline measurements minus measurements recorded at each time interval after eye rubbing (for IOP), and for each corneal location (for CT)] and comparison were then made between groups (allergic versus control) for differences in any observed effects. RESULTS Within groups, baseline mean IOPs in the allergic patient-group (14.2±3.0 mm Hg) and in the control group (13.1±1.9 mm Hg) were similar at all times, after eye rubbing (P >0.05, for all). The maximum reduction in IOP was 0.8 mm Hg in the control subjects and the maximum increase was also 0.8 mm Hg in the allergic subjects. Between groups (allergic versus control), the changes in IOP remained under 1 mm Hg at all times (P=0.2) after 30min of eye rubbing. Between 0 and 30min of CT measurements after eye rubbing, the mean central CT (CCT), inferior CT (ICT), superior CT (SCT), temporal CT (TCT) and nasal CT (NCT) did not vary significantly from baseline values in the control and allergic-subject groups (P>0.05, for both). Between both groups, changes in CT were similar at all locations (P>0.05) except for the TC which was minimally thinner by about 4.4 µm (P=0.001) in the allergic subjects than in the control subjects, 30min following 30s of eye rubbing. CONCLUSION IOP measured in allergic subjects after 30s of habitual eye rubbing was comparable with that obtained in normal subjects at all times between 0 and 30min. Although, CT in the allergic subjects were similar to those of the control subjects at all times, it varied between +10 and -7.5 µm following eye rubbing, with the temporal cornea showing consistent reductions in thickness in the subjects with allergy. However, this reduction was minimal and was considered to not be clinically relevant.

Ocular changes associated with accommodation in myopes and emmetropes

This thesis examines the short-term changes occurring in a number of the eye's structures during reading tasks, and explores how these changes differ between normal eyes, and those with short-sightedness (myopia). This research revealed changes in the shape and thickness of a number of the eye's structures during near work, and aspects of these changes showed differences associated with myopia. These findings have potentially important implications for our understanding of the role of near work in the development and progression of myopia.

Tissue-engineered fibroin scaffolds for ocular tissue reconstruction

The silk protein fibroin (Bombyx mori) provides a potential substrate for use in ocular tissue reconstruction. We have previously demonstrated that transparent membranes produced from fibroin support cultivation of human limbal epithelial (HLE) cells (Tissue Eng A. 14(2008)1203-11). We extend this body of work to studies of limbal mesenchymal stromal cell (L-MSC) growth on fibroin. Also, we investigate the ability to produce a fibroin dual-layer scaffold with an upper HLE layer and lower L-MSC layer...

Effect of ocular hypotony secondary to cyclodialysis cleft on corneal topography

PURPOSE: To report the changes in corneal topography in 2 cases of ocular hypotony induced by cyclodialysis cleft after blunt trauma, which were successfully treated by argon laser photocoagulation. METHODS: For both patients, a full ophthalmic clinical examination and corneal topography were performed before and after argon laser cleft closure. RESULTS: In the first case, the corneal topography showed 3.81-D astigmatism at 96 degrees, which was reduced to 1.1 D at 124 degrees 1 week after treatment and 0.66 D at 122 degrees at 3 weeks after treatment. In the second case, the corneal astigmatism was 3.91 D at 104 degrees, which decreased to 1.44 D at 104 degrees and 0.35 D at 118 degrees at 1 week and 4 months after treatment, respectively. CONCLUSIONS: In both cases, the with-the-rule astigmatism reduced significantly after successful closure of the cleft and an increase in intraocular pressure.

Expression of cytochrome P450 enzymes and metabolism of timolol in human ocular tissue

Glaucoma is a group of progressive optic neuropathies causing irreversible blindness if not diagnosed and treated in the early state of progression. Disease is often, but not always, associated with increased intraocular pressure (IOP), which is also the most important risk factor for glaucoma. Ophthlamic timolol preparations have been used for decades to lower increased intraocular pressure (IOP). Timolol is locally well tolerated but may cause e.g. cardiovascular and pulmonary adverse effects due to systemic absorption. It has been reported that approximately 80% of a topically administered eye drop is systemically absorbed. However, only limited information is available on timolol metabolism in the liver or especially in the human eye. The aim of this work was to investigate metabolism of timolol in human liver and human ocular tissues. The expression of drug metabolizing cytochrome P450 (CYP) enzymes in the human ciliary epithelial cells was studied. The metabolism of timolol and the interaction potential of timolol with other commercially available medicines were investigated in vitro using different liver preparations. The absorption of timolol to the aqueous humor from two commercially available products: 0.1% eye gel and 0.5% eye drops and the presence of timolol metabolites in the aqueous humor were investigated in a clinical trial. Timolol was confirmed to be metabolized mainly by CYP2D6 as previously suggested. Potent CYP2D6 inhibitors especially fluoxetine, paroxetine and quinidine inhibited the metabolism of timolol. The inhibition may be of clinical significance in patients using ophthalmic timolol products. CYP1A1 and CYP1B1 mRNAs were expressed in the human ciliary epithelial cells. CYP1B1 was also expressed at protein level and the expression was strongly induced by a known potent CYP1B1 inducer 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The CYP1B1 induction is suggested to be mediated by aryl hydrocarbon receptor (AHR). Low levels of CYP2D6 mRNA splice variants were expressed in the human ciliary epithelial cells and very low levels of timolol metabolites were detected in the human aqueous humor. It seems that negligible amount of CYP2D6 protein is expressed in the human ocular tissues. Timolol 0.1% eye gel leads to aqueous humor concentration high enough to achieve therapeutic effect. Inter-individual variation in concentrations is low and intraocular as well as systemic safety can be increased when using this product with lower timolol concentration instead of timolol 0.5% eye drops.

Biometry of eyes in type 1 diabetes

This is a comprehensive study of a large range of biometric and optical parameters in people with type 1 diabetes. The parameters of 74 people with type 1 diabetes and an age matched control group were assessed. Most of the people with diabetes had low levels of neuropathy, retinopathy and nephropathy. Marginal or no significant differences were found between groups for corneal shape, corneal thickness, pupil size, and pupil decentrations. Relative to the control group, the diabetes group demonstrated smaller anterior chamber depths, more curved lenses, greater lens thickness and lower lens equivalent refractive index. While the optics of diabetic eyes make them appear as older eyes than those of people of the same age without diabetes, the differences did not increase significantly with age. Age-related changes in the optics of the eyes of people with diabetes need not be accelerated if the diabetes is well controlled.

Tissue thickness calculation in ocular optical coherence tomography

Thickness measurements derived from optical coherence tomography (OCT) images of the eye are a fundamental clinical and research metric, since they provide valuable information regarding the eye’s anatomical and physiological characteristics, and can assist in the diagnosis and monitoring of numerous ocular conditions. Despite the importance of these measurements, limited attention has been given to the methods used to estimate thickness in OCT images of the eye. Most current studies employing OCT use an axial thickness metric, but there is evidence that axial thickness measures may be biased by tilt and curvature of the image. In this paper, standard axial thickness calculations are compared with a variety of alternative metrics for estimating tissue thickness. These methods were tested on a data set of wide-field chorio-retinal OCT scans (field of view (FOV) 60° x 25°) to examine their performance across a wide region of interest and to demonstrate the potential effect of curvature of the posterior segment of the eye on the thickness estimates. Similarly, the effect of image tilt was systematically examined with the same range of proposed metrics. The results demonstrate that image tilt and curvature of the posterior segment can affect axial tissue thickness calculations, while alternative metrics, which are not biased by these effects, should be considered. This study demonstrates the need to consider alternative methods to calculate tissue thickness in order to avoid measurement error due to image tilt and curvature.

Light exposure and eye growth in childhood

PURPOSE The purpose of this study was to examine the relationship between objectively measured ambient light exposure and longitudinal changes in axial eye growth in childhood. METHODS A total of 101 children (41 myopes and 60 nonmyopes), 10 to 15 years of age participated in this prospective longitudinal observational study. Axial eye growth was determined from measurements of ocular optical biometry collected at four study visits over an 18-month period. Each child’s mean daily light exposure was derived from two periods (each 14 days long) of objective light exposure measurements from a wrist-worn light sensor. RESULTS Over the 18-month study period, a modest but statistically significant association between greater average daily light exposure and slower axial eye growth was observed (P ¼ 0.047). Other significant predictors of axial eye growth in this population included children’s refractive error group (P < 0.001), sex (P < 0.01), and age (P < 0.001). Categorized according to their objectively measured average daily light exposure and adjusting for potential confounders (age, sex, baseline axial length, parental myopia, nearwork, and physical activity), children experiencing low average daily light exposure (mean daily light exposure: 459 6 117 lux, annual eye growth: 0.13 mm/y) exhibited significantly greater eye growth than children experiencing moderate (842 6 109 lux, 0.060 mm/y), and high (1455 6 317 lux, 0.065 mm/y) average daily light exposure levels (P ¼ 0.01). CONCLUSIONS In this population of children, greater daily light exposure was associated with less axial eye growth over an 18-month period. These findings support the role of light exposure in the documented association between time spent outdoors and childhood myopia.

Reconstruction of the ocular surface using biomaterial templates

This chapter discusses the effect on vision of a large group of pathological conditions, known as ocular surface disorders (OSDs), and presents the therapeutic strategies to reconstruct the abnormal ocular surface. If left untreated, most of the OSDs will lead to partial or total loss of eyesight, especially when limbal stem cell deficiency is involved. An overview of various treatment strategies is presented, with the emphasis on the development of the ex vivo expansion of corneal limbal epithelial cells (presumed to be progenitor or stem cells) and the creation of transplantable epithelial constructs. The use of naturally derived biomaterials (collagen, fibrin, amnion, etc.) or synthetic polymers (polylactides, thermoresponsive polymers, etc.) as substrata in these constructs is critically analyzed. Emphasis is placed on the templates from silk proteins, which are being developed by the authors.