Accommodation and intraocular pressure

The relationship between accommodation and intraocular pressure (lOP) has not been addressed as a research question for over 20 years, when measurement of both of these parameters was less advanced than today. Hence the central aim of this thesis was to evaluate the effects of accommodation on lOP. The instrument of choice throughout this thesis was the Pulsair EasyEye non-contact tonometer (NCT) due principally to its slim-line design which allowed the measurement of lOP in one eye and simultaneous stimulation of accommodation in the other eye. A second reason for using the Pulsair EasyEye NCT was that through collaboration with the manufacturers (Keeler, UK) the instrument's operational technology was made accessible. Hence, the principle components underpinning non-contact lOP measures of 0.1mmHg resolution (an order of magnitude greater than other methods) were made available. The relationship between the pressure-output and corneal response has been termed the pressure-response relationship, aspects of which have been shown to be related to ocular biometric parameters. Further, analysis of the components of the pressure-response relationship together with high-speed photography of the cornea during tonometry has enhanced our understanding of the derivation of an lOP measure with the Pulsair EasyEye NCT. The NCT samples the corneal response to the pressure pulse over a 19 ms cycle photoelectronically, but computes the subject's lOP using the data collected in the first 2.34 ms. The relatively instantaneous nature of the lOP measurement renders the measures susceptible to variations in the steady-state lOP caused by the respiratory and cardiac cycles. As such, the variance associated with these cycles was minimised by synchronising the lOP measures with the cardiac trace and maintaining a constant pace respiratory cycle at 15 breathes/minute. It is apparent that synchronising the lOP measures with the peak, middle or trough of the cardiac trace significantly reduced the spread of consecutive measures. Of the 3 locations investigated, synchronisation with the middle location demonstrated the least variance (coeflicient of variation = 9.1%) and a strong correlation (r = 0.90, p = <0.001) with lOP values obtained with Goldmann contact tonometry (n = 50). Accordingly lOP measures synchronised with the middle location of the cardiac cycle were taken in the RE while the LE fixated low (L; zero D), intermediate (I; 1.50 D) and high (H; 4 D) accommodation targets, Quasi-continuous measures of accommodation responses were obtained during the lOP measurement period using the portable infrared Grand Seiko FR-5000 autorefractor. The lOP reduced between L and I accommodative levels by approximately 0.61 mmHg (p <0.00 I). No significant reduction in IOP between L and H accommodation levels was elicited (p = 0.65) (n = 40). The relationship between accommodation and lOP was characterised by substantial inter-subject variations. Myopes demonstrated a tendency to show a reduction in IOP with accommodation which was significant only with I accommodation levels when measured with the NCT (r = 0.50, p = 0.01). However, the relationship between myopia and lOP change with accommodation reached significance for both I (r = 0.61, p= 0.003) and H (r = 0.531, p= 0.0 1) accommodation levels when measured with the Ocular blood Flow Analyser (OBFA). Investigation of the effects of accommodation on the parameters measured by the OBFA demonstrated that with H accommodation levels the pulse amplitude (PA) and pulse rate (PR) responses differed between myopes and emmetropes (PA: p = 0.03; PR: p = 0.004). As thc axial length increased there was a tendency for the pulsatile ocular blood flow (POBF) to reduce with accommodation, which was significant only with H accommodation levels (r = 0.38, p = 0.02). It is proposed that emmetropes arc able to regulate the POBF responses to changes in ocular perfusion pressure caused by changes in lOP with I (r = 0.77, p <0.001) and H (r = 0.73, p = 0.001) accommodation levels. However, thc relationship between lOP and POBF changes in the myopes was not correlated for both I (r = 0.33, p = 0.20) and H (r = 0.05, p = 0.85) accommodation levels. The thesis presents new data on the relationships between accommodation, lOP and parameters of the OBFA,: and provides evidence for possible lOP and choroidal blood flow regulatory mechanisms. Further the data highlight possible deficits in the vascular regulation of the myopic eye during accommodation, which may play a putative role in the aetiology of myopia development.

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.

Biomechanical aspects of the anterior segment in human myopia

The thesis investigates the relationship between the biomechanical properties of the anterior human sclera and cornea in vivo using Schiotz tonometry (ST), rebound tonometry (RBT, iCare) and the Ocular Response Analyser (ORA, Reichert). Significant differences in properties were found to occur between scleral quadrants. Structural correlates for the differences were examined using Partial Coherent Interferometry (IOLMaster, Zeiss), Optical Coherent tomography (Visante OCT), rotating Scheimpflug photography (Pentacam, Oculus) and 3-D Magnetic Resonance Imaging (MRI). Subject groups were employed that allowed investigation of variation pertaining to ethnicity and refractive error. One hundred thirty-five young adult subjects were drawn from three ethnic groups: British-White (BW), British-South-Asian (BSA) and Hong-Kong-Chinese (HKC) comprising non-myopes and myopes. Principal observations: ST demonstrated significant regional variation in scleral resistance a) with lowest levels at quadrant superior-temporal and highest at inferior-nasal; b) with distance from the limbus, anterior locations showing greater resistance. Variations in resistance using RBT were similar to those found with ST; however the predominantly myopic HKC group had a greater overall mean resistance when compared to the BW-BSA group. OCT-derived scleral thickness measurements indicated the sclera to be thinner superiorly than inferiorly. Thickness varied with distance from the corneolimbal junction, with a decline from 1 to 2 mm followed by a successive increase from 3 to 7 mm. ORA data varied with ethnicity and refractive status; whilst axial length (AL) was associated with corneal biometrics for BW-BSA individuals it was associated with IOP in the HKC individuals. Complex interrelationships were found between ORA Additional-Waveform-Parameters and biometric data provided by the Pentacam. OCT indicated ciliary muscle thickness to be greater in myopia and more directly linked to posterior ocular volume (from MRI) than AL. Temporal surface areas (SAs, from MRI) were significantly smaller than nasal SAs in myopic eyes; globe bulbosity (from MRI) was constant across quadrants.

Shape of the posterior vitreous chamber in human emmetropia and myopia

PURPOSE - To compare posterior vitreous chamber shape in myopia to that in emmetropia. METHODS - Both eyes of 55 adult subjects were studied, 27 with emmetropia (MSE =-0.55; <+0.75D; mean +0.09 ±0.36D) and 28 with myopia (MSE -5.87 ±2.31D). Cycloplegic refraction was measured with a Shin Nippon autorefractor and anterior chamber depth and axial length with a Zeiss IOLMaster. Posterior vitreous chamber shapes were determined from T2-weighted MRI (3-Tesla) using procedures previously reported by our laboratory. 3-D surface model coordinates were assigned to nasal, temporal, superior and inferior quadrants and plotted in 2-D to illustrate the composite shape of respective quadrants posterior to the second nodal point. Spherical analogues of chamber shape were constructed to compare relative sphericity between refractive groups and quadrants. RESULTS - Differences in shape occurred in the region posterior to points of maximum globe width and were thus in general accord with an equatorial model of myopic expansion. Shape in emmetropia is categorised distinctly as that of an oblate ellipse and in myopia as an oblate ellipse of significantly less degree such that it approximates to a sphere. There was concordance between shape and retinotopic projection of respective quadrants into right, left, superior and inferior visual fields. CONCLUSIONS - The transition in shape from oblate ellipse to sphere with axial elongation supports the hypothesis that myopia may be a consequence of equatorial restriction associated with biomechanical anomalies of the ciliary apparatus. The synchronisation of quadrant shapes with retinotopic projection suggests that binocular growth is coordinated by processes that operate beyond the optic chiasm.

Myopia control with orthokeratology contact lenses in Spain (MCOS):refractive and biometric changes

PURPOSE. To compare axial length growth between white children with myopia wearing orthokeratology contact lenses (OK) and distance single-vision spectacles (SV) over a 2-year period. METHODS. Subjects 6 to 12 years of age with myopia -0.75 to -4.00 diopters of sphere (DS) and astigmatism ≤1.00 diopters of cylinder (DC) were prospectively allocated OK or SV correction. Measurements of axial length (Zeiss IOLMaster), corneal topography, and cycloplegic refraction were taken at 6-month intervals. RESULTS. Thirty-one children were fitted with OK and 30 with SV. Following 24 months, axial length increased significantly over time for both the OK group (0.47 mm) and SV group (0.69 mm; P < 0.001), with a significant interaction between time and group (P = 0.05) reflecting a greater increase in the SV group. Significant differences in refraction were found over time, between groups and for the interaction between time and group for spherical (all P < 0.001) but not cylindrical components of refraction (all P > 0.05). Significantly greater corneal flattening was evident in the OK group for the flatter and steeper corneal powers and for corneal shape factor (all P ≤0.05). CONCLUSIONS. Orthokeratology contact lens wear reduces axial elongation in comparison to distance single-vision spectacles in children. © 2012 The Association for Research in Vision and Ophthalmology, Inc.

Impact of senescence and disease on the structural and functional performance of the visual pathway

The diagnosis and monitoring of ocular disease presents considerable clinical difficulties for two main reasons i) the substantial physiological variation of anatomical structure of the visual pathway and ii) constraints due to technical limitations of diagnostic hardware. These are further confounded by difficulties in detecting early loss or change in visual function due to the masking of disease effects, for example, due to a high degree of redundancy in terms of nerve fibre number along the visual pathway. This thesis addresses these issues across three areas of study: 1. Factors influencing retinal thickness measures and their clinical interpretation As the retina is the principal anatomical site for damage associated with visual loss, objective measures of retinal thickness and retinal nerve fibre layer thickness are key to the detection of pathology. In this thesis the ability of optical coherence tomography (OCT) to provide repeatable and reproducible measures of retinal structure at the macula and optic nerve head is investigated. In addition, the normal physiological variations in retinal thickness and retinal nerve fibre layer thickness are explored. Principal findings were: • Macular retinal thickness and optic nerve head measurements are repeatable and reproducible for normal subjects and diseased eyes • Macular and retinal nerve fibre layer thickness around the optic nerve correlate negatively with axial length, suggesting that larger eyes have thinner retinae, potentially making them more susceptible to damage or disease • Foveola retinal thickness increases with age while retinal nerve fibre layer thickness around the optic nerve head decreases with age. Such findings should be considered during examination of the eye with suspect pathology or in long-term disease monitoring 2. Impact of glucose control on retinal anatomy and function in diabetes Diabetes is a major health concern in the UK and worldwide and diabetic retinopathy is a major cause of blindness in the working population. Objective, quantitative measurements of retinal thickness. particularly at the macula provide essential information regarding disease progression and the efficacy of treatment. Functional vision loss in diabetic patients is commonly observed in clinical and experimental studies and is thought to be affected by blood glucose levels. In the first study of its kind, the short term impact of fluctuations in blood glucose levels on retinal structure and function over a 12 hour period in patients with diabetes are investigated. Principal findings were: • Acute fluctuations in blood glucose levels are greater in diabetic patients than normal subjects • The fluctuations in blood glucose levels impact contrast sensitivity scores. SWAP visual fields, intraocular pressure and diastolic pressure. This effect is similar for type 1 and type 2 diabetic patients despite the differences in their physiological status. • Long-term metabolic control in the diabetic patient is a useful predictor in the fluctuation of contrast sensitivity scores. • Large fluctuations in blood glucose levels and/or visual function and structure may be indicative of an increased risk of development or progression of retinopathy 3. Structural and functional damage of the visual pathway in glaucomatous optic neuropathy The glaucomatous eye undergoes a number of well documented pathological changes including retinal nerve fibre loss and optic nerve head damage which is correlated with loss of functional vision. In experimental glaucoma there is evidence that glaucomatous damage extends from retinal ganglion cells in the eye, along the visual pathway, to vision centres in the brain. This thesis explores the effects of glaucoma on retinal nerve fibre layer thickness, ocular anterior anatomy and cortical structure, and its correlates with visual function in humans. Principal findings were: • In the retina, glaucomatous retinal nerve fibre layer loss is less marked with increasing distance from the optic nerve head, suggesting that RNFL examination at a greater distance than traditionally employed may provide invaluable early indicators of glaucomatous damage • Neuroretinal rim area and retrobulbar optic nerve diameter are strong indicators of visual field loss • Grey matter density decreases at a rate of 3.85% per decade. There was no clear evidence of a disease effect • Cortical activation as measured by fMRI was a strong indicator of functional damage in patients with significant neuroretinal rim loss despite relatively modest visual field defects These investigations have shown that the effects of senescence are evident in both the anterior and posterior visual pathway. A variety of anatomical and functional diagnostic protocols for the investigation of damage to the visual pathway in ocular disease are required to maximise understanding of the disease processes and thereby optimising patient care.

Profile of anisometropia and aniso-astigmatism in children; prevalence and association with age, ocular biometric measures, and refractive status

Purpose. We describe the profile and associations of anisometropia and aniso-astigmatism in a population-based sample of children. Methods. The Northern Ireland Childhood Errors of Refraction (NICER) study used a stratified random cluster design to recruit a representative sample of children from schools in Northern Ireland. Examinations included cycloplegic (1% cyclopentolate) autorefraction, and measures of axial length, anterior chamber depth, and corneal curvature. ?2 tests were used to assess variations in the prevalence of anisometropia and aniso-astigmatism by age group, with logistic regression used to compare odds of anisometropia and aniso-astigmatism with refractive status (myopia, emmetropia, hyperopia). The Mann-Whitney U test was used to examine interocular differences in ocular biometry. Results. Data from 661 white children aged 12 to 13 years (50.5% male) and 389 white children aged 6 to 7 years (49.6% male) are presented. The prevalence of anisometropia =1 diopters sphere (DS) did not differ statistically significantly between 6- to 7-year-old (8.5%; 95% confidence interval [CI], 3.9–13.1) and 12- to 13-year-old (9.4%; 95% CI, 5.9–12.9) children. The prevalence of aniso-astigmatism =1 diopters cylinder (DC) did not vary statistically significantly between 6- to 7-year-old (7.7%; 95% CI, 4.3–11.2) and 12- to 13-year-old (5.6%; 95% CI, 0.5–8.1) children. Anisometropia and aniso-astigmatism were more common in 12- to 13-year-old children with hyperopia =+2 DS. Anisometropic eyes had greater axial length asymmetry than nonanisometropic eyes. Aniso-astigmatic eyes were more asymmetric in axial length and corneal astigmatism than eyes without aniso-astigmatism. Conclusions. In this population, there is a high prevalence of axial anisometropia and corneal/axial aniso-astigmatism, associated with hyperopia, but whether these relations are causal is unclear. Further work is required to clarify the developmental mechanism behind these associations.

Ocular biometric correlates of ciliary muscle thickness in human myopia

Purpose - Anterior segment optical coherent tomography (AS-OCT) is used to further examine previous reports that ciliary muscle thickness (CMT) is increased in myopic eyes. With reference to temporal and nasal CMT, interrelationships between biometric and morphological characteristics of anterior and posterior segments are analysed for British-White and British-South-Asian adults with and without myopia. Methods - Data are presented for the right eyes of 62 subjects (British-White n = 39, British-South-Asian n = 23, aged 18–40 years) with a range of refractive error (mean spherical error (MSE (D)) -1.74 ± 3.26; range -10.06 to +4.38) and separated into myopes (MSE (D) <-0.50, range -10.06 to -0.56; n = 30) and non-myopes (MSE (D) =-0.50, -0.50 to +4.38; n = 32). Temporal and nasal ciliary muscle cross-sections were imaged using a Visante AS-OCT. Using Visante software, manual measures of nasal and temporal CMT (NCMT and TCMT respectively) were taken in successive posterior 1 mm steps from the scleral spur over a 3 mm distance (designated NCMT1, TCMT1 et seq). Measures of axial length and anterior chamber depth were taken with an IOLMaster biometer. MSE and corneal curvature (CC) measurements were taken with a Shin-Nippon auto-refractor. Magnetic resonance imaging was used to determine total ocular volume (OV) for 31 of the original subject group. Statistical comparisons and analyses were made using mixed repeated measures anovas, Pearson's correlation coefficient and stepwise forward multiple linear regression. Results - MSE was significantly associated with CMT, with thicker CMT2 and CMT3 being found in the myopic eyes (p = 0.002). In non-myopic eyes TCMT1, TCMT2, NCMT1 and NCMT2 correlated significantly with MSE, AL and OV (p < 0.05). In contrast, myopic eyes failed generally to exhibit a significant correlation between CMT, MSE and axial length but notably retained a significant correlation between OV, TCMT2, TCMT3, NCMT2 and NCMT3 (p < 0.05). OV was found to be a significantly better predictor of TCMT2 and TCMT3 than AL by approximately a factor of two (p < 0.001). Anterior chamber depth was significantly associated with both temporal and nasal CMT2 and CMT3; TCMT1 correlated positively with CC. Ethnicity had no significant effect on differences in CMT. Conclusions - Increased CMT is associated with myopia. We speculate that the lack of correlation in myopic subjects between CMT and axial length, but not between CMT and OV, is evidence that disrupted feedback between the fovea and ciliary apparatus occurs in myopia development.

Validity and repeatability of the Aladdin ocular biometer

Aim To assess the accuracy and reproducibility of biometry undertaken with the Aladdin (Topcon, Tokyo, Japan) in comparison with the current gold standard device, the IOLMaster 500 (Zeiss, Jena, Germany). Setting University Eye Clinic, Birmingham, UK and Refractive Surgery Centre, Kiel, Germany. Methods The right eye of 75 patients with cataracts and 22 healthy participants were assessed using the two devices. Measurements of axial length (AL), anterior chamber depth (ACD) and keratometry (K) were undertaken with the Aladdin and IOLMaster 500 in random order by an experienced practitioner. A second practitioner then obtained measurements for each participant using the Aladdin biometer in order to assess interobserver variability. Results No statistically significant differences ( p≥0.05) between the two biometers were found for average difference (AL)±95% CI=0.01±0.06 mm), ACD (0.00 ±0.11 mm) or mean K values (0.08±0.51 D). Furthermore, interobserver variability was very good for each parameter (weighted κ≥0.85). One patient's IOL powers could not be calculated with either biometer measurements, whereas a further three could not be analysed by the IOLMaster 500. The IOL power calculated from the valid measurements was not statistically significantly different between the biometers (p=0.842), with 91% of predictions within±0.25 D. Conclusions The Aladdin is a quick, easy-to-use biometer that produces valid and reproducible results that are comparable with those obtained with the IOLMaster 500.

Factors preventing myopia progression with orthokeratology correction

PURPOSE: To examine which baseline measurements constitute predictive factors for axial length growth over 2 years in children wearing orthokeratology contact lenses (OK) and single-vision spectacles (SV). METHODS: Sixty-one children were prospectively assigned to wear either OK (n = 31) or SV (n = 30) for 2 years. The primary outcome measure (dependent variable) was axial length change at 2 years relative to baseline. Other measurements (independent variables) were age, age of myopia onset, gender, myopia progression 2 years before baseline and baseline myopia, anterior chamber depth, corneal power and shape (p value), and iris and pupil diameters as well as parental refraction. The contribution of all independent variables to the 2-year change in axial length was assessed using univariate and multivariate regression analyses. RESULTS: After univariate analyses, smaller increases in axial length were found in the OK group compared to the SV group in children who were older, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had less myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris diameter, had larger pupil sizes, and had lower levels of parental myopia (all p < 0.05). In multivariate analyses, older age and greater corneal power were associated with smaller increases in axial length in the OK group (both p < 0.05), whereas in SV wearers, smaller iris diameter was associated with smaller increases in axial length (p = 0.021). CONCLUSIONS: Orthokeratology is a successful treatment option in controlling axial elongation compared to SV in children of older age, had earlier onset of myopia, were female, had lower rate of myopia progression before baseline, had lower myopia at baseline, had longer anterior chamber depth, had greater corneal power, had more prolate corneal shape, had larger iris and pupil diameters, and had lower levels of parental myopia. © American Academy of Optometry.

Nearwork-induced transient myopia (NITM) in anisometropia

Objective: To assess the magnitude of nearwork-induced transient myopia (NITM) under binocular viewing conditions separately in each eye of individuals with mild to moderate anisometropia to determine the relationship between NITM and their interocular refractive error. Methods: Forty-three children and young adults with anisometropia [cycloplegic spherical equivalent (SE) difference >1.00 D] were tested (ages 9-28 years). NITM was measured with binocular viewing separately in each eye after binocularly performing a sustained near task (5 D) for 5 min incorporating a cognitive demand using an open-field, infrared autorefractor (Grand-Seiko, WAM-5500). Data were averaged over 10 s bins for 3 min in each eye. Initial NITM, its decay time (DT), and its decay area (DA) were determined. A-scan ultrasound ocular biometry was also performed to determine the axial length of each eye. Results: The more myopic eye exhibited increased initial NITM, DT, and DA as compared to the less myopic eye (0.21 ± 0.16 D vs 0.15 ± 0.13 D, p = 0.026; 108.4 ± 64.3 secs vs 87.0 ± 65.2 secs, p = 0.04; and 17.6 ± 18.7 D*secs vs 12.3 ± 15.7 D*secs, p = 0.064), respectively. The difference in DA and the difference in SE between the more versus less myopic eye were significantly correlated (r = 0.31, p = 0.044). Furthermore, 63% (27/43), 56% (24/43), and 70% (30/43) of the more myopic eyes exhibited increased initial NITM, longer DT, and larger DA, respectively, than found in the less myopic eye. Conclusions: In approximately two-thirds of the anisometropic individuals, the initial NITM and its decay area were significantly increased in the more myopic eye as compared to the less myopic eye. NITM may play an important role in the development of interocular differences in myopia, although a causal relationship is yet to be established. Furthermore, the findings have potentially important implications regarding accommodative control and interocular accommodative responsitivity in anisometropia, in particular for anisomyopia. © 2013 The College of Optometrists.

Short-term changes in ocular biometry and refraction after discontinuation of long-term orthokeratology

OBJECTIVE: To assess refractive and biometric changes 1 week after discontinuation of lens wear in subjects who had been wearing orthokeratology (OK) contact lenses for 2 years. METHODS: Twenty-nine subjects aged 6 to 12 years and with myopia of -0.75 to -4.00 diopters (D) and astigmatism of ≤1.00 D participated in the study. Measurements of axial length and anterior chamber depth (Zeiss IOLMaster), corneal power and shape, and cycloplegic refraction were taken 1 week after discontinuation and compared with those at baseline and after 24 months of lens wear. RESULTS: A hyperopic shift was found at 24 months relative to baseline in spherical equivalent refractive error (+1.86±1.01 D), followed by a myopic shift at 1 week relative to 24 months (-1.93±0.92 D) (both P<0.001). Longer axial lengths were found at 24 months and 1 week in comparison to baseline (0.47±0.18 and 0.51±0.18 mm, respectively) (both P<0.001). The increase in axial length at 1 week relative to 24 months was statistically significant (0.04±0.06 mm; P=0.006). Anterior chamber depth did not change significantly over time (P=0.31). Significant differences were found between 24 months and 1 week relative to baseline and between 1-week and 24-month visits in mean corneal power (-1.68±0.80, -0.44±0.32, and 1.23±0.70 D, respectively) (all P≤0.001). Refractive change at 1 week in comparison to 24 months strongly correlated with changes in corneal power (r=-0.88; P<0.001) but not with axial length changes (r=-0.09; P=0.66). Corneal shape changed significantly between the baseline and 1-week visits (0.15±0.10 D; P<0.001). Corneal shape changed from a prolate to a more oblate corneal shape at the 24-month and 1-week visits in comparison to baseline (both P≤0.02) but did not change significantly between 24 months and 1 week (P=0.06). CONCLUSIONS: The effects of long-term OK on ocular biometry and refraction are still present after 1-week discontinuation of lens wear. Refractive change after discontinuation of long-term OK is primarily attributed to the recovery of corneal shape and not to an increase in the axial length.

Refractive and biometric changes with silicone hydrogel contact lenses

Purpose. This study reports data from an 18-month longitudinal study of neophyte contact lens wearers and compares changes in ocular refraction and biometry induced by daily wear and continuous wear of two different silicone hydrogel (SiH) materials. Methods. Forty-five subjects were enrolled in the study and randomly assigned to wear one of the two silicone hydrogel materials: Lotrafilcon A or Balafilcon A lenses on either a daily or continuous wear basis. Measurements of objective refraction, axial length, anterior chamber depth, corneal curvature, and the rate of peripheral corneal flattening were performed before and 1, 3, 6, 12, and 18 months after initial fitting. Results. Mean spherical equivalent refractive error increased in the myopic direction in all contact lens groups across time (p < 0.001). Axial length was the main biometric contributor to the development of myopia. After 18 months of lens wear, subjects in the Lotrafilcon A group showed the greater mean increase in myopia (i.e., -0.50 D). Conclusions. The results of this study show that increases in myopia, similar if not higher than those found to occur normally in young adult noncontact lens wearers, still occur with silicone hydrogel contact lens wear. The main biometric contributor to the progression of myopia was an increase in axial length. Differences between our results and those of previous studies with silicone hydrogel contact lenses could be attributed to the differing populations used in which both age and occupation may have played a role. Copyright © 2005 American Academy of Optometry.

A new non-contact optical device for ocular biometry

Background: A new commercially available device (IOLMaster, Zeiss Instruments) provides high resolution non-contact measurements of axial length (using partial coherent interferometry), anterior chamber depth, and corneal radius (using image analysis). The study evaluates the validity and repeatability of these measurements and compares the findings with those obtained from instrumentation currently used in clinical practice. Method: Measurements were taken on 52 subjects (104 eyes) aged 18-40 years with a range of mean spherical refractive error from +7.0 D to -9.50 D. IOLMaster measurements of anterior chamber depth and axial length were compared with A-scan applanation ultrasonography (Storz Omega) and those for corneal radius with a Javal-Schiötz keratometer (Topcon) and an EyeSys corneal videokeratoscope. Results: Axial length: the difference between IOLMaster and ultrasound measures was insignificant (0.02 (SD 0.32) mm, p = 0.47) with no bias across the range sampled (22.40-27.99 mm). Anterior chamber depth: significantly shorter depths than ultrasound were found with the IOLMaster (-0.06 (0.25) mm, p <0.02) with no bias across the range sampled (2.85-4.40 mm). Corneal radius: IOLMaster measurements matched more closely those of the keratometer than those of the videokeratoscope (mean difference -0.03 v -0.06 mm respectively), but were more variable (95% confidence 0.13 v 0.07 mm). The repeatability of all the above IOLMaster biometric measures was found to be of a high order with no significant bias across the measurement ranges sampled. Conclusions: The validity and repeatability of measurements provided by the IOLMaster will augment future studies in ocular biometry.

The development and growth of tissues derived from cranial neural crest and primitive mesoderm is dependent on the ligation status of retinoic acid receptor γ:evidence that retinoic acid receptor γ functions to maintain stem/progenitor cells in the absence of retinoic acid

Retinoic acid (RA) signaling is important to normal development. However, the function of the different RA receptors (RARs)-RARα, RARβ, and RARγ-is as yet unclear. We have used wild-type and transgenic zebrafish to examine the role of RARγ. Treatment of zebrafish embryos with an RARγ-specific agonist reduced somite formation and axial length, which was associated with a loss of hoxb13a expression and less-clear alterations in hoxc11a or myoD expression. Treatment with the RARγ agonist also disrupted formation of tissues arising from cranial neural crest, including cranial bones and anterior neural ganglia. There was a loss of Sox 9-immunopositive neural crest stem/progenitor cells in the same anterior regions. Pectoral fin outgrowth was blocked by RARγ agonist treatment. However, there was no loss of Tbx-5-immunopositive lateral plate mesodermal stem/progenitor cells and the block was reversed by agonist washout or by cotreatment with an RARγ antagonist. Regeneration of the caudal fin was also blocked by RARγ agonist treatment, which was associated with a loss of canonical Wnt signaling. This regenerative response was restored by agonist washout or cotreatment with the RARγ antagonist. These findings suggest that RARγ plays an essential role in maintaining stem/progenitor cells during embryonic development and tissue regeneration when the receptor is in its nonligated state.