Purpose: Hyper-reflective superficial cells were an unexpected finding while examining the corneal epithelium using confocal microscopy (CM), during an MSc thesis conducted in 2006 at the University of Waterloo, Canada. The author1 suggested that the appearance of these hyper-reflective cells could be associated with solution induced corneal staining (SICS) that was also observed in those participants who had manifested these hyper-reflective cells. However, this hypothesis has not been reported in the literature. This thesis aimed to investigate variables that could possibly predict the appearance of hyper-reflective superficial cells. These investigated variables were the effect of: contact lenses, contact lens solutions, lens/solution combinations, long-term use of certain contact lenses and solutions, age, dry eye symptom, topical anaesthetics and sodium fluorescein. In addition to this, the normal superficial epithelium of controls was defined. Methods: CM images of the superficial epithelium were obtained during the various experiments from: 32 non-contact lens wearing participants, 18 post-menopausal participants symptomatic of dry eye and 18 post-menopausal age-matched asymptomatic women and 147 adapted soft contact lens wearers. For one experiment CM was performed with the contact lens in situ, making the use of a topical anaesthetic unnecessary. Superficial cellular appearance of CM images was graded using a custom grading scale. Hyper-reflective cells were counted. Corneal staining was assessed using sodium fluorescein. Results: Results obtained during the various experiments revealed that hyper-reflective cells predominately appeared with the use of a specific lens/solution combination. Also, the number of hyper-reflective cells peaked after two hours of lens wear. It was also shown that when hyper-reflective cells occurred during an experiment, not every participant who was exposed to that specific lens/solution combination manifested hyper-reflective cells. Also, a great deal of inter-subject variability in observed numbers of hyper-reflective cells was noted. Conclusion: In conclusion, this thesis established that the hyper-reflective cells that were observed by Harvey were reproducible and may co-occur with corneal staining induced by a specific lens/solution interaction

Purposes: To use optical coherence tomography (OCT) to image and quantify the effect of various corneal conditions, in terms of corneal, stromal and epithelial thickness, and light backscatter. To assess the changes caused by overnight orthokeratology (Corneal Refractive Therapy; CRT^TM) lens wear, keratoconus and laser in-situ keratomileusis (LASIK) refractive surgery, each of which may lead to topographical alterations in corneal thickness either by temporary moulding, degeneration, or permanent laser ablation, respectively. <br /><br /> Methods: Topographical thickness of the cornea was measured using OCT in all studies. The CRT^TM studies investigated myopic and hyperopic treatment, throughout the day. The myopic studies followed lens wear over a 4 week period, which was extended to 12 months, and investigated the thickness changes produced by two lenses of different oxygen transmissibility. CRT^TM for hyperopia (CRTH^TM) was evaluated after a single night of lens wear. <br /><br /> In the investigation of keratoconus, OCT corneal thickness values were compared to those obtained from Orbscan II (ORB) and ultrasound pachymetry (UP). A new fixation device was constructed to aid in the measurement of topographical corneal and epithelial thickness along 8 directions of gaze. Pachymetry maps were produced for the normal non-lens wearing cornea, and compared with the rigid gas permeable (RGP) lens wearing cornea and the keratoconic cornea. <br /><br /> Thickness changes prior to, and following LASIK were measured and monitored throughout six months. Myopic and hyperopic correction was investigated individually, as the laser ablation profiles differ for each type of procedure. The LASIK flap interface was also evaluated by using light backscatter data to monitor healing. <br /><br /> Results: Following immediate lens removal after myopic CRT^TM, the central cornea swelled less than the periphery, with corneal swelling recovering to baseline levels within 3 hours. The central epithelium decreased and mid-peripheral epithelium increased in thickness, with a more gradual recovery throughout the day. There also seemed to be an adaptation effect on the cornea and epithelium, showing a reduced amount of change by the end of the 4 week study period. The thickness changes did not alter dramatically during the 12 month extended study. In comparing the two lens materials used for myopic CRT^TM (Dk/t 91 vs. 47), there were differences in stromal swelling, but no differences in the central epithelial thinning caused by lens wear. There was a statistically insignificant asymmetry in mid-peripheral epithelial thickening between eyes, with the lens of lower Dk causing the greater amount of thickening. Hyperopic CRT^TM produced a greater increase in central stromal and central epithelial thickness than the mid-periphery. Once again, the stroma recovered faster than the epithelium, which remained significantly thicker centrally for at least six hours following lens removal. <br /><br /> Global pachymetry measurements of the normal cornea and epithelium found the periphery to be thicker than the centre. The superior cornea and epithelium was thicker than the inferior. In the measurement of the keratoconic cornea, OCT and ORB correlated well in corneal thickness values. UP measured greater values of corneal thickness. The keratoconic epithelium was thinner than normal, and more so over the apex of the cone than at the centre. The location of the cone was most commonly found in the inferior temporal region. Central epithelial thickness was thinner in keratoconics than in RGP lens wearers, which in turn was thinner than in non-lens wearers. <br /><br /> Following LASIK surgery for both myopia and hyperopia, the topographical OCT thickness profiles showed stromal thinning in the areas of ablation. The central myopic cornea showed slight regression at 6 months. During early recovery, epithelial thickness increased centrally in hyperopes and mid-peripherally in myopes. By the end of the 6 month study, mid-peripheral epithelial thickness was greater than the centre in both groups of subjects. The light backscatter profiles after LASIK showed a greater increase in backscatter on the anterior side of the flap interface (nearer the epithelium), than the posterior side (in the mid-stroma) during healing. The flap interface was difficult to locate in the OCT images at 6 months. <br /><br /> Conclusion: All the CRT^TM lenses used in this project produced more corneal swelling than that seen normally overnight without lens wear. In order for these lenses to be worn safely for long periods of time without affecting the health of the cornea, they need to be manufactured from the highest oxygen transmissible material available. The long-term effect of thinning on the epithelium's barrier properties needs to be monitored closely. <br /><br /> Global topographical thickness of the cornea and epithelium was measured using OCT in normal, RGP lens wearing and keratoconic eyes. Corneal and epithelial thickness was not symmetrical across meridians. The epithelium of RGP lens wearers was slightly thinner than normal, but not as thin as in keratoconics, suggesting that the epithelial change seen in keratoconus is mainly due to the condition. <br /><br /> Post-LASIK corneal and epithelial thickness profiles were not the same for myopic and hyperopic subjects, since the ablation patterns vary. Epithelial thickening in the mid-periphery had not recovered by six months in myopes or hyperopes, possibly indicating epithelial hyperplasia. Light backscatter profiles were used to monitor the recovery of the LASIK flap interface, showing the band of light backscatter around the flap interface to decrease as the cornea healed.

Abstract Both in the closed and open eye state the superior limbus is covered by the upper lid. This region is of physiological interest and clinical importance because in chronic hypoxia, neovascularization of the cornea commonly occurs here. The limbal region in general is additionally of importance as the stem cells which are the source of the new corneal cells are located in the epithelium of the limbus and these are vital for normal functioning and are affected under certain adverse conditions. Purpose: In this experiment I examined corneal morphology in the limbal area and in particular under the upper lid in order to primarily examine the variation in the corneal limbal epithelial and total thickness as well as epithelial and endothelial cell density. Methods: I measured 30 eyes OD/OS (chosen randomly) of thirty healthy subjects aged from 18 to 55 years in the first study and twelve participants in the second study, with refractive error ≤ ±4 D and astigmatism ≤ 2 D. The thickness and cell density of five positions: superior, inferior, temporal, nasal limbal and central cornea was determined with optical coherence tomography (OCT) and confocal microscopy. At least three scans of each position were taken in both studies with OCT. At least 40 of 100 adjacent sagittal scans of each image were measured using OCT software program. In the confocal study, image J software was used to determine cell densities. Results: The epithelial and corneal limbal thickness were significantly thicker than the epithelial and central corneal thickness (p<0.05). The limbal, inferior cornea is thinner than the three other positions and the temporal region of the cornea is the thickest both in epithelial and total cornea. Epithelial cell density was significantly lower in the superior cornea than the four other positions. There was no significant difference in the endothelial cell density. Conclusions: Using OCT with high resolution and cross-sectional imaging capability and confocal microscope with high magnification, I found that the limbal cornea is significantly thicker than the central cornea both in total and in epithelial thickness. In the limbus, one might expect the superior cornea (under the lid) to be thickest (because of the expected hypoxia) whereas I found the temporal cornea was thickest. The epithelial cell density was lower in the superior cornea but there was no significant difference in cell densities in the endothelium. Further morphological investigation is of interest.

Purpose: Hyper-reflective superficial cells were an unexpected finding while examining the corneal epithelium using confocal microscopy (CM), during an MSc thesis conducted in 2006 at the University of Waterloo, Canada. The author1 suggested that the appearance of these hyper-reflective cells could be associated with solution induced corneal staining (SICS) that was also observed in those participants who had manifested these hyper-reflective cells. However, this hypothesis has not been reported in the literature. This thesis aimed to investigate variables that could possibly predict the appearance of hyper-reflective superficial cells. These investigated variables were the effect of: contact lenses, contact lens solutions, lens/solution combinations, long-term use of certain contact lenses and solutions, age, dry eye symptom, topical anaesthetics and sodium fluorescein. In addition to this, the normal superficial epithelium of controls was defined. Methods: CM images of the superficial epithelium were obtained during the various experiments from: 32 non-contact lens wearing participants, 18 post-menopausal participants symptomatic of dry eye and 18 post-menopausal age-matched asymptomatic women and 147 adapted soft contact lens wearers. For one experiment CM was performed with the contact lens in situ, making the use of a topical anaesthetic unnecessary. Superficial cellular appearance of CM images was graded using a custom grading scale. Hyper-reflective cells were counted. Corneal staining was assessed using sodium fluorescein. Results: Results obtained during the various experiments revealed that hyper-reflective cells predominately appeared with the use of a specific lens/solution combination. Also, the number of hyper-reflective cells peaked after two hours of lens wear. It was also shown that when hyper-reflective cells occurred during an experiment, not every participant who was exposed to that specific lens/solution combination manifested hyper-reflective cells. Also, a great deal of inter-subject variability in observed numbers of hyper-reflective cells was noted. Conclusion: In conclusion, this thesis established that the hyper-reflective cells that were observed by Harvey were reproducible and may co-occur with corneal staining induced by a specific lens/solution interaction

A detailed understanding of the corneal biomechanical response is an important prerequisite to understanding corneal diseases such as keratoconus and for placing the empirical equations used in refractive surgery on a physical basis. We have assembled a combined nonlinear optical microscopy (NLOM) and optical coherence microscopy (OCM) imaging system to simultaneously capture coregistered volumetric images of corneal morphology and biochemistry. Fudicial markers visible in the OCM volume enabled the calculation of strains for multiple depth layers in rabbit cornea. The results revealed a depth dependent strain distribution, with smaller strains in the anterior stroma and larger strains in the posterior stroma. The stress-strain curves can be grouped readily by depth into three groups: anterior (~20%), transitional mid (~40%), and posterior (~40%). Cross-sectional images of collagen lamellae, visible in NLOM, showed inhomogeneous collagen structure and its response to intraocular pressure along the anterior-posterior direction. The inhomogeneities correlate well with the noted heterogeneous corneal mechanical properties. The combined NLOM-OCM system can measure corneal microstructure and mechanical response uniquely, thus providing a microstructural understanding of corneal response to changes of collagen structure.

The corneal wound healing response involves the activation of keratocytes to proliferate from a quiescent phenotype. The mitogens that cause the initial transformation of the quiescent keratocytes to the active phenotype have not been identified. Even though serum is commonly used to replicate this in vitro, the cornea is avascular and therefore likely not exposed to serum. In the first part of this dissertation, a DMEM/F12 extract of corneal stromas was made and shown to stimulate keratocyte proliferation in both a dose-dependent and cell-density dependent manner. This extract contains mitogens that differ from the mitogens present in serum based on their effect on keratocytes and their biochemical characteristics. Culture in extract replicates in vitro the changes observed during the activation of keratocytes in the wound-healing phase.The corneal stroma contains an extensive extracellular matrix that consists primarily of collagens and proteolgycans. This matrix is maintained and secreted by the keratocytes, cells with unique characteristics lost during the activation observed at wound healing. The second part of this dissertation aims to develop a defined culture medium that maintains the keratocyte phenotype during proliferation. Keratocytes were cultured in serum-free medium and the effect of the growth factors on the markers for the keratocyte phenotype determined. Only insulin was shown to stimulate cell proliferation in a consistent manner, while maintaining commonly accepted keratocyte markers. When this defined culture medium was supplemented with ascorbic acid to study collagen synthesis, a marked increase in both collagen synthesis and keratan sulfate proteoglycan accumulation was measured. This newly developed culture medium, containing insulin and ascorbate, allows for cell growth, maintains the keratocyte markers, and could be used to study the native, non-activated keratocyte phenotype in culture.This dissertation shows that the culture media described herein replicate in vitro all the phenotypes observed during the corneal wound healing response in vivo. These culture media, in turn, could be used to obtain more knowledge about the different keratocyte phenotypes, and how they could be manipulated in culture. (329 words)

Lasers pose a safety hazards both to skin and particularly to something you value highly - your vision. The increasingly widespread use of IR wavelengths laser systems requires awareness with the potential hazards associated with the misuse of these valuable products. The principal goal of this research is to integrate experimental and theoretical descriptions of thermal response of skin and cornea to IR wavelength laser irradiation to yield a basis for the dosimetry of laser-tissue interaction. The threshold radiant exposures for various spot sizes and exposure durations were investigated on in vivo skin and cornea for 2.0 [mu]m laser irradiation. Similar study was also conducted on in vivo skin using 1.214 [mu]m laser and compared with 2.0 [mu]m results. This PhD study has, for the first time, linked temperature response, histopathology, and the more common "minimal visible lesion (MVL)" endpoint into what can be a meaningful comparison of rate process models for injury. Based on experimental data, a finite-element optical-thermal-damage model was developed. Histological damage was measured and modeled using sub-threshold, threshold, and super-threshold 2.0 [mu]m laser powers. The data provided experimental evidence of the correlation of sub-threshold histological change to visible threshold lesion for the irradiation condition of this study. Moreover, the computer model, supported by experimental validation, ensured that rate process models were used correctly in the prediction of "MVL" thresholds which were based upon a finite damage extent and not necessarily central surface layer damage. Thermal image method was employed to measure the absorption coefficient of in vivo skin at 2.0 [mu]m, at which wavelength scattering can be ignored. At laser wavelengths below 1.4 [mu]m where scattering cannot be ignored, an ameliorative method was explored to measure absorption and reduce scattering of in vivo tissue by combining pulse photothermal radiometry (PPTR) and diffuse reflectance (DR) measurements.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Introduction: The measurement of tear film stability/regularity is very critical in the diagnosis of dry eye. The tear breakup time, which is used as a diagnostic tool in diagnosing dry eye, is very subjective in nature and variations among individual clinicians exists. The exact mechanism of the tear breakup is also unclear due to the involvement of so many other factors other than the tear film itself. As the prevalence of dry eye is increasing, the need for an objective technique which can be used universally to differentiate between dry eye and normal values increases. Studies have shown that aberrations can be used as an objective technique in diagnosing dry eye, as there is a direct involvement of the tear film in the optics of the eye. However, very few studies have studied the dynamic nature of the anterior surface using aberrations and suggested using dynamic surface aberrations as an objective measure of surface quality. Hence, a series of studies were conducted to understand the aberrations produced by the anterior surface of the eye (tear film and corneal surface) and to measure objectively the anterior surface quality using surface aberrometry. The objectives of each study chapter are as follows: Chapter 3 i): To obtain the noise associated with the instrument using a non-dynamic measuring surface, and ii) to design appropriate acquisition settings for the measurements with ocular surface. Chapter 4: To determine ??) the spectral characteristics of the Placido disc light sources of two corneal analysers, ????) the thermal characteristic for a variety of inanimate objects, human ocular surface and the adnexa in the presence of Placido disc light source at normal working distance, and ??????) to compare the ocular surface aberrations obtained using both the corneal analysers Chapter 5: To determine i) the optimal method for acquisition with respect to normal physiological processes, by examining the blink regimen and head position that elicits the most consistent response over the largest region on repeated measurement; and i??) the largest region selected for analysis by investigating the effect on the individual and summary aberration metrics of the inclusion of non-measurement areas (i.e. where the Placido disc cannot be projected onto the cornea or contact lens). The proportion of non-measurement area that elicits a significantly different result will be determined. Chapter 6: To evaluate ??) a new method of analyzing dynamic ocular surface aberrations using segmented liner regression, and ????) the inter-ocular characteristics of the dynamic ocular surface aberrations using the segmented linear regression. Methods: Chapter 3: The characteristics of the surface aberrometer and the noise associated with the measurements of surface aberrations were evaluated using a non-dynamic surface (model eye). Measurements were obtained in different frame rates and focus positions to evaluate the optimal acquisition technique. At each focus position, a set of three repeated measurements were obtained to analyse the repeatability of the measurements obtained using a surface aberrometer. Chapter 4: The spectral characteristics of the Placido disc light source were obtained by using a PR650 SpectraScan photometer and the thermal characteristics of the objects were obtained using THI-500 non-contact infrared thermometer. The surface aberration measurements were compared between the corneal analysers. The spectral measures were obtained from the light sources, whereas the thermal measures were obtained from three different surfaces and surface of the eye and adnexa of ten participants. The dynamic anterior surface aberrations were obtained after obtaining the thermal measurements from the surface of the eye. Chapter 5: Twelve participants were enrolled by screening twenty participants. Participants were screened with their habitual lenses for contact lens wettability and non-invasive tear breakup time (NITBUT) without contact lenses. The participants were enrolled according to the inclusion and exclusion criteria and categorized into normal and dry eye group for study visits. The measurements of NITBUT and surface aberrations were obtained with and without contact lenses, and study lens wettability were also obtained in two visits on consecutive days. The surface aberration measurements were obtained in natural and forced blinking condition and in two different head positions. All the measurements were randomized between eye and between instruments. Chapter 6: Seventeen non- symptomatic and non- contact lens participants were recruited in this study. NITBUT and dynamic anterior surface aberration measurements were obtained. The order of the measurements was randomized between the eyes. Two open intervals of at least 10 sec and a maximum of 15 sec were used in the analysis of segmented fit. The dynamic vertical prism coefficients and higher order aberrations were used for the analysis. Results: Chapter 3: i. Data acquisition at an inter-frame interval of 0.25s gave the least number of dropped frames across focus positions, therefore this is the preferred frame rate for data acquisition. ii. Data obtained in the initial ~15s reflects the focusing procedure and needs to be manually removed prior to analysis of tear dynamics. iii. Even in the optimal focus position there were significant (small) differences in the distributions between repeated measures. For this reason repeated samples have to be obtained where possible. iv. The green and red focus positions showed the most consistency within repeated measurements. The variability of the measurements was also more similar between the red and green focus positions than the blue focus positions, both at the extreme positions of defocus and with incremental defocus away from the optimal focus position. When obtaining the dynamic sampling of human ocular surface measurements, the optimal position of focus should be obtained at the blink such that as the tear film dissipates between blinks the measurements are obtained in the (relatively) red focus position. Chapter 4: i. CA200 is the preferred device because of the consistent luminance. ii. Although aberrations were not significantly different between devices, the HOA RMS were higher with the CA200 and, combined with different luminance and possible tear response, indicates the devices are not interchangeable. In both instruments, there was no indication that there was a thermal response induced by the power of the light source. Therefore, this aspect of the source does not likely contribute to any difference in the aberrations measured by the two devices Chapter 5: i. Obtain data in the straight-ahead position, as there is no significant increase in target size with head turn. ii. With the CA100F, the forced blink paradigm is preferred as this enables blink dynamics to be examined. With the CA200F, either forced or natural blink paradigms are interpretable for tear dynamics. iii. Differentiation between dry eye and normal groups was best determined with the slope of the RMS aberrations within a blink. iv. Differentiation between performance with and without a contact lens in the dry eye and normal groups was best determined by analysing the width of the confidence interval of the moving average. Chapter 6: i. The location breakpoints one and two are significantly different between eye, open eye interval and order of the measurements for both vertical prism and HOA RMS values. ii. The highest positive slope for the HOA RMS was, on average, higher in the second eye measured (p= 0.0407) and tended to occur later after the blink (p= 0.0676). iii. The location of breakpoint 2 is not significantly different from the NITBUT values (p>0.05), even though the correlation was found to be low and not significant. iv. The average HOA RMS for segmented fit parameter intervals of vertical prism was found to be higher in the second open eye interval compared to first open eye interval. Conclusion: From the results of each chapter, it was observed that choosing the blink paradigm is very important to obtain and analyse the dynamic anterior surface aberrations. Choosing a forced blink paradigm (chapter 5) was showed to be useful when the information regarding blink location were not available. The repeatability of the measurements using a non-dynamic surface (chapter 3) shows that the measurements of surface aberrations are repeatable and it is important to choose a criterion closer to the natural tear film dynamics to obtain more repeatable measurements of anterior surface aberrations (chapter 4, 5 and 6). It also shows that the three phased segmented linear regression techniques can be used to analyse the anterior surface aberrations. The segmented linear regression technique was able to differentiate different stages of the tear film and the location of the second breakpoint calculated using segmented regression was closer to the clinical values of tear breakup time, indicating a possible use of segmented linear regression as an objective measure of surface quality.

The cornea is the most powerful refractive component of the eye and as such, subtle changes in corneal shape can cause substantial changes in the optical characteristics of the eye. Monocular diplopia has previously been linked to corneal distortion following near work in various studies but has not been investigated in detail. The work reported in this thesis has investigated the optical effects of corneal distortions caused by eyelid forces and demonstrated that several corneal higher and lower order Zernike wavefront aberrations can change following reading. Measuring subtle changes in corneal topography requires the highest possible instrument accuracy, while software analysis tools should be able to detect and highlight those subtle changes with high reliability. The effect of ocular microfluctuations on the qualitative and quantitative analysis of corneal topography was investigated. A technique was developed to measure tilt, displacement, and cyclotorsion in multiple videokeratographs from the same cornea. This information was used to reposition each videokeratograph according to the average position of a sample of multiple measurements. The corneal topography of ten subjects was measured 20 times each, using videokeratoscopy. The RMSE calculated from difference between single videokeratographs and the average videokeratograph decreased by an average of 24.6 % for the ten subjects' data. The method can improve the precision performance of videokeratoscopy in multiple measurements of corneal topography. A study was undertaken, to investigate whether there are significant changes in corneal topography during accommodation in normal corneas and corneas that are pathologically thinner due to keratoconus. This was done to eliminate the possibility that changes in corneal aberrations associated with near work could be at least partly due to corneal changes caused by the effects of accommodation. A videokeratoscope was modified to present an accommodation stimulus that was coaxial with the instrument's measurement axis. Six subjects with normal corneas and four subjects with keratoconus were studied. In the initial analysis it was found that a number of the subjects showed significant changes in corneal topography as accommodation changed. However further analysis showed a significant group mean excyclotorsion of the topography maps for both accommodation stimuli compared with the 0 D stimulus. When the excyclotorsion was accounted for, no clear evidence of statistically significant changes in corneal topography as a result of accommodation were found. A small ocular excyclotorsion typically accompanies accommodation and this changes the relative orientation of the topography of the cornea. To investigate the effects of eyelid pressure on corneal shape and corneal aberrations during reading, twenty young subjects with normal ocular health were recruited. Cornea1 topography of one eye was measured with a videokeratoscope prior to reading and then again after a 60 minute reading task. Twelve of the twenty corneas showed significant changes in central topography immediately following reading. The location of the changes corresponded closely to the position and angle of the subject's eyelids during reading. Within the central region of the cornea there were significant changes in corneal wavefront Zernike coefficients, the root-mean-square error, overall refractive power and astigmatism. The changes observed in corneal topography appear to be directly related to the force exerted by the eyelids during reading. These findings may have important implications for the definition of refractive status and may also aid in the understanding of the relationship between reading and the development of refractive errors. To study whether corneal distortions after reading significantly differ between refractive error groups, corneal aberrations were measured before and after a period of reading, for a group of ten young progressing myopes and a group of ten young stable emmetropes. The major difference between the two groups was the location and magnitude of the corneal distortions, which had a significantly larger effect on central corneal optics in the myopic group compared to the emmetropic group. A significantly smaller palpebral aperture for the myopic group in the reading gaze position was the cause of this difference. The experiments described in this thesis have shown that numerous corneal characteristics can change due to eyelid forces during near work. The eye was shown to undergo a small cyclotorsion during higher levels of accommodation. There was a shift in direction of against the rule astigmatism of the cornea following reading and a change was found for primary vertical coma and trefoil. The changes in corneal shape following reading appear to be different in myope versus emmetropic refractive error groups. These findings are important for our understanding of the stability of the refractive error of the eye and could have important implications for refractive error development.