The role of cognitive and visual abilities as predictors in the Multifactorial Model of Driving Safety

Objective The current study evaluated part of the Multifactorial Model of Driving Safety to elucidate the relative importance of cognitive function and a limited range of standard measures of visual function in relation to the Capacity to Drive Safely. Capacity to Drive Safely was operationalized using three validated screening measures for older drivers. These included an adaptation of the well validated Useful Field of View (UFOV) and two newer measures, namely a Hazard Perception Test (HPT), and a Hazard Change Detection Task (HCDT). Method Community dwelling drivers (n = 297) aged 65–96 were assessed using a battery of measures of cognitive and visual function. Results Factor analysis of these predictor variables yielded factors including Executive/Speed, Vision (measured by visual acuity and contrast sensitivity), Spatial, Visual Closure, and Working Memory. Cognitive and Vision factors explained 83–95% of age-related variance in the Capacity to Drive Safely. Spatial and Working Memory were associated with UFOV, HPT and HCDT, Executive/Speed was associated with UFOV and HCDT and Vision was associated with HPT. Conclusion The Capacity to Drive Safely declines with chronological age, and this decline is associated with age-related declines in several higher order cognitive abilities involving manipulation and storage of visuospatial information under speeded conditions. There are also age-independent effects of cognitive function and vision that determine driving safety.

Influence of field size on pupil diameter under photopic and mesopic light levels

Purpose: We investigated the interaction between adapting field size and luminance on pupil diameter when cones alone (photopic) or rods and cones (mesopic) were active. Method: Circular achromatic targets (1o to 24o diameter) were presented to eight young participants on a rectangular projector screen. The accommodative influence on pupil diameter was minimized using cycloplegia in the fixing right eye and the consensual pupil reflex was measured in the left eye. Target luminance was adjusted for each stimulus such that corneal flux density (product of field area and luminance) was constant at 3600 cd.deg2m-2 (photopic condition) and 1.49 cd.deg2m-2 (mesopic condition). Results: There were no statistically significant effects of adaptive field size on pupil diameter for either condition. Conclusion: If corneal flux density is kept constant, there will be no change in pupil diameter as the size of the stimulus field increases at either mesopic or photopic lighting levels up to at least 24°.

Corneal nerve structure and function as markers of diabetic neuropathy

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterisation and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression and assess new therapies. This thesis evaluates novel corneal methods of assessing diabetic neuropathy. Over the past several years two new non-invasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy (CCM) allows quantification of corneal nerve parameters and non-contact corneal aesthesiometry (NCCA), the presumed functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and with automatic analysis paradigms developed, are suitable for clinical settings. Each has advantages and disadvantages over established techniques for assessing diabetic neuropathy. New information is presented regarding measurement bias of CCM images, and a unique sampling paradigm and associated accuracy determination method of combinations is described. A novel high-speed corneal nerve mapping procedure has been developed and application of this procedure in individuals with neuropathy has revealed regions of sub-basal nerve plexus that dictate further evaluation, as they appear to show earlier signs of damage than the central region of the cornea that has to date been examined. The discriminative capacity of corneal sensitivity measured by NCCA is revealed to have reasonable potential as a marker of diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Dynamics of rod and cone photoreceptor interactions under mesopic light levels

Visual adaptation regulates contrast sensitivity during dynamically changing light conditions (Crawford, 1947; Hecht, Haig & Chase, 1937). These adaptation dynamics are unknown under dim (mesopic) light levels when the rod (R) and long (L), medium (M) and short (S) wavelength cone photoreceptor classes contribute to vision via interactions in shared non-opponent Magnocellular (MC), chromatically opponent Parvocellular (PC) and Koniocellular (KC) visual pathways (Dacey, 2000). This study investigated the time-course of adaptation and post-receptoral pathways mediating receptor specific rod and cone interactions under mesopic illumination. A four-primary photostimulator (Pokorny, Smithson & Quinlan, 2004) was used to independently control the activity of the four photoreceptor classes and their post-receptoral visual athways in human observers. In the first experiment, the contrast sensitivity and time-course of visual adaptation under mesopic illumination were measured for receptoral (L, S, R) and post-receptoral (LMS, LMSR, L-M) stimuli. An incremental (Rapid-ON) sawtooth conditioning pulse biased detection to ON-cells within the visual pathways and sensitivity was assayed relative to pulse onset using a briefly presented incremental probe that did not alter adaptation. Cone.Cone interactions with luminance stimuli (L cone, LMS, LMSR) reduced sensitivity by 15% and the time course of recovery was 25± 5ms-1 (μ ± SEM). PC mediated (+L-M) chromatic stimuli sensitivity loss was less (8%) than for luminance and recovery was slower (μ = 2.95 ± 0.05 ms-1), with KC mediated (S cone) chromatic stimuli showing a high sensitivity loss (38%) and the slowest recovery time (1.6 ± 0.2 ms-1). Rod-Rod interactions increased sensitivity by 20% and the time course of recovery was 0.7 ± 0.2 ms-1 (μ ± SD). Compared to these interaction types, Rod-Cone interactions reduced sensitivity to a lesser degree (5%) and showed the fastest recovery (μ = 43 ± 7 ms-1). In the second experiment, rod contribution to the magnocellular, parvocellular and koniocellular post-receptoral pathways under mesopic illumination was determined as a function of incremental stimulus duration and waveform (rectangular; sawtooth) using a rod colour match procedure (Cao, Pokorny & Smith, 2005; Cao, Pokorny, Smith & Zele, 2008a). For a 30% rod increment, a cone match required a decrease in [L/(L+M)] and an increase in [L+M] and [S/(L+M)], giving a greenish-blue and brighter appearance for probe durations of 75 ms or longer. Probe durations less than 75 ms showed an increase in [L+M] and no change in chromaticity [L/(L+M) or S/(L+M)], uggesting mediation by the MC pathway only for short duration rod stimuli. s We advance previous studies by determining the time-course and nature of photoreceptor specific retinal interactions in the three post-receptoral pathways under mesopic illumination. In the first experiment, the time-course of adaptation for ON cell processing was determined, revealing opponent cell facilitation in chromatic PC and KC pathways. The Rod-Rod and Rod-Cone data identify previously unknown interaction types that act to maintain contrast sensitivity during dynamically changing light conditions and improve the speed of light adaptation under mesopic light levels. The second experiment determined the degree of rod contribution to the inferred post-eceptoral pathways as a function of the temporal properties of the rod signal. r The understanding of the mechanisms underlying interactions between photoreceptors under mesopic illumination has implications for the study of retinal disease. Visual function has been shown to be reduced in persons with age-related maculopathy (ARM) risk genotypes prior to clinical signs of the disease (Feigl, Cao, Morris & Zele, 2011) and disturbances in rod-mediated adaptation have been shown in early phases of ARM (Dimitrov, Guymer, Zele, Anderson & Vingrys, 2008; Feigl, Brown, Lovie-Kitchin & Swann, 2005). Also, the understanding of retinal networks controlling vision enables the development of international lighting standards to optimise visual performance nder dim light levels (e.g. work-place environments, transportation).

Research initiatives to improve the visibility and hence safety of road workers at night-time

Research has demonstrated the benefits that clothing incorporating retroreflective markers can provide in significantly improving visibility and reducing accidents, especially at night. Adding biomotion markings to standard vests can enhance the night-time conspicuity of roadway workers by capitalizing on perceptual capabilities.

Current status and future prospects for cultured limbal tissue transplants in Australia and New Zealand

Cultured limbal tissue transplants have become widely used over the last decade as a treatment for limbal stem cell deficiency (LSCD). While the number of patients afflicted with LSCD in Australia and New Zealand is considered to be relatively low, the impact of this disease on quality of life is so severe that the potential efficacy of cultured transplants has necessitated investigation. We presently review the basic biology and experimental strategies associated with the use of cultured limbal tissue transplants in Australia and New Zealand. In doing so, we aim to encourage informed discussion on the issues required to advance the use of cultured limbal transplants in Australia and New Zealand. Moreover, we propose that a collaborative network could be established to maintain access to the technology in conjunction with a number of other existing and emerging treatments for eye diseases.

GABAergic modification of myopic and hyperopic ocular tissue effects on scleral fibroblast growth

Purpose: Myopia is a common eye disorder affecting up to 90% of children in South East Asia and 30% of the population worldwide. Myopia of high severity is a leading cause of blindness around the world (4th to 5th most common). Changes and remodelling of the sclera i.e. increase cellular proliferation & increase protein synthesis within scleral cells (↑ scleral DNA) and thinning and lose of extracellular matrix of sclera (↓ scleral GAG synthesis) have been linked to myopic eye growth in animal models. Signals acting on the sclera are thought to originate in the retina, and are modulated by the retinal pigment epithelium (RPE) with limited evidence suggesting that the RPE can modify scleral cell growth in culture. However, the mechanism of retinal signal transmission and the role of posterior eye cup tissue, including the RPE, in mediating changes in scleral fibroblast growth during myopia development are unclear. Retinal transmitter systems are critically involved in pathways regulating eye growth, which ultimately lead to alterations in the sclera if eye size is to change. A dopaminergic agonist and muscarinic antagonists decrease the proliferation of scleral chondrocytes when co-cultured with chick’s retinal pigment epithelium (RPE). GABA receptors have recently been localised to chick sclera. We therefore hypothesised that posterior eye cup tissue from myopic eyes would stimulate and from hyperopic eyes would inhibit growth of scleral fibroblasts in vitro and that GABAergic agents could directly interact with scleral cells or indirectly modify the effects of myopic and hyperopic posterior eye cup tissue on scleral fibroblast growth. Method: Fibroblastic cells obtained from 8-day-old chick sclera were used to establish cell banks. Two major experiments were performed. Experiment 1: To determine if posterior eye cup tissues from myopic eye stimulates and hyperopic eye inhibits scleral cell proliferation, when co-cultured with scleral cells in vitro. This study comprised two linked experiments, i) monocular visual treatments of FDM (form-deprivation myopia), LIM (lens-induced myopia) and LIH (lens-induced hyperopia) with assessment of the effect of full punch eye cup tissue on DNA and GAG synthesis by cultured chick scleral fibroblasts, and ii) binocular visual treatments comprising LIM and LIH with assessment of the effect of individual layers of eye cup tissues (neural retina, RPE and choroid) on cultured chick scleral fibroblasts. Visual treatment was applied for 3 days. Experiment 2: To determine the direct interaction of GABA agents on scleral cell growth and to establish whether GABA agents modify the stimulatory/inhibitory effect of myopic and hyperopic posterior eye cup tissues on cultured scleral cell growth in vitro. Two linked experiments were performed. i) GABA agonists (muscimol and baclofen) and GABA antagonists (bicuculine (-), CGP46381 and TPMPA) were added to scleral cell culture medium to determine their direct effect on scleral cells. ii) GABAergic agents (agonists and antagonists) were administered to scleral fibroblasts co-cultured with posterior eye cup tissue (retina, RPE, retina/RPE, RPE/choroid). Ocular tissues were obtained from chick eyes wearing +15D (LIH) or -15D lenses (LIM) for 3 days. In both experiments, tissues were added to hanging cell culture insert (pore size 1.0ìm) placed over each well of 24 well plates while scleral cells were cultured in DMEM/F12, Glutamax (Gibco) plus 10% FBS and penicillin/streptomycin (50U/ml)) and fungizone (1.25ug/ml) (Gibco), at seeding density of 30,000 cells/well at the bottom of the well and allowed to grow for 3 days. Scleral cells proliferation rate throughout the study was evaluated by determining GAG and DNA content of scleral cells using Dimethylmethylene blue (DMMB) dye and Quant-iTTm Pico Green® dsDNA reagent respectively. Results and analysis: Based on DNA and GAG content, there was no significant difference in tissue effect of LIM and LIH eyes on scleral fibroblast growth (DNA: 8.4 ± 1.1μg versus 9.3 ± 2.3 μg, p=0.23; GAG: 10.13 ± 1.4 μg versus 12.67 ± 1.2 μg, F2,23=6.16, p=0.0005) when tissues were obtained from monocularly treated chick eyes (FDM or +15D lens or -15D lens over right eyes with left eyes untreated) and co-cultured as full punch. When chick eyes were treated binocularly with -15D lens (LIM) right eye and +15D lens (LIH) left eyes and tissue layers were separated, the retina from LIM eyes did not stimulate scleral cell proliferation compared to LIH eyes (DNA: 27.2 ± 6.7 μg versus 23.2 ± 1.5 μg, p=0.23; GAG: 28.1 ±3.7 μg versus 28.7 ± 4.2 μg, p=0.21). Similarly, the LIH and LIM choroid did not produce a differential effect based on DNA (LIM 46.9 ± 6.4 μg versus LIH 53.5 ± 4.7 μg, p=0.18), however the choroid from LIH eyes induced higher scleral GAG content than from LIM eyes (32.5 ± 6.7 μg versus 18.9 ± 1.2 μg, p=0.023). In contrast, the RPE from LIM eyes caused a significant increase in fibroblast proliferation whereas the RPE from LIH eyes was relatively inhibitory (72.4 ± 6.3 μg versus 27.9 ± 2.3 μg, F1, 6=69.99, p=0.0005). GAG data were opposite to DNA data e.g. the RPE from LIH eyes increased (33.7 ± 7.9 μg) while the RPE from LIM eyes decreased (28.2 ± 3.0 μg) scleral cell growth (F1, 6=13.99, p=0.010). Based on DNA content, GABA agents had a small direct effect on scleral cell growth; GABA agonists increased (21.4 ± 1.0% and 18.3 ± 1.0% with muscimol and baclofen, p=0.0021), whereas GABA antagonists decreased fibroblast proliferation (-23.7 ± 0.9% with bicuculine & CGP46381 and -28.1 ± 0.5% with TPMPA, p=0.0004). GABA agents also modified the effect of LIM and LIH tissues (p=0.0005).The increase in proliferation rate of scleral fibroblasts co-cultured with tissues (RPE, retina, RPE/retina and RPE/choroid) from LIM treated eyes was enhanced by GABA agonists (muscimol: 27.4 ± 1.2%, 35.8 ± 1.6%, 8.4 ± 0.3% and 11.9 ± 0.6%; baclofen: 27.0 ± 1.0%, 15.8 ± 1.5%, 16.8 ± 1.2% and 15.4 ± 0.4%, p=0.014) whereas GABA antagonists further reduced scleral fibroblasts growth (bicuculine: -52.5 ± 2.5%, -36.9 ± 1.4%, -37.5 ± 0.6% and -53.7 ± 0.9%; TPMPA: 57.3 ± 1.3%, -15.7 ± 1.2%, -33.5 ± 0.4% and -45.9 ± 1.5%; CGP46381: -51.9 ± 1.6%, -28.5 ± 1.5%, -25.4 ± 2.0% and -45.5 ± 1.9% respectively, p=0.0034). GAG data were opposite to DNA data throughout the experiment e.g. GABA agonists further inhibited while antagonists relatively enhanced scleral fibroblasts growth for both LIM and LIH tissue co-culture. The effect of GABA agents was relatively lower (p=0.0004) for tissue from LIH versus LIM eyes but was in a similar direction. There was a significant drug effect on all four tissue types e.g. RPE, retina, RPE/retina and RPE/choroid for both LIM and LIH tissue co-culture (F20,92=3.928, p=0.0005). However, the effect of GABA agents was greatest in co-culture with RPE tissue (F18,36=4.865, p=0.0005). Summary and Conclusion: 1) Retinal defocus signals are transferred to RPE and choroid which then exert their modifying effect on scleral GAG and DNA synthesis either through growth stimulating factors or directly interacting with scleral cells in process of scleral remodeling during LIM and LIH visual conditions. 2) GABAergic agents affect the proliferation of scleral fibroblasts both directly and when co-cultured with ocular tissues in vitro.

A yellow filter improves response times to low-contrast targets and traffic hazards

Purpose Anecdotal evidence suggests that some sunglass users prefer yellow tints for outdoor activities, such as driving, and research has suggested that such tints improve the apparent contrast and brightness of real-world objects. The aim of this study was to establish whether yellow filters resulted in objective improvements in performance for visual tasks relevant to driving. Methods Response times of nine young (age [mean ± SD], 31.4 ± 6.7 years) and nine older (age, [mean ± SD], 74.6 ± 4.8) adults were measured using video presentations of traffic hazards (driving hazard perception task) and a simple low-contrast grating appeared at random peripheral locations on a computer screen. Response times were compared when participants wore a yellow filter (with and without a linear polarizer) versus a neutral density filter (with and without a linear polarizer). All lens combinations were matched to have similar luminance transmittances (˜27%). Results In the driving hazard perception task, the young but not the older participants responded significantly more rapidly to hazards when wearing a yellow filter than with a luminance-matched neutral density filter (mean difference, 450 milliseconds). In the low-contrast grating task, younger participants also responded more quickly for the yellow filter condition but only when combined with a polarizer. Although response times increased with increasing stimulus eccentricity for the low-contrast grating task, for the younger participants, this slowing of response times with increased eccentricity was reduced in the presence of a yellow filter, indicating that perception of more peripheral objects may be improved by this filter combination. Conclusions Yellow filters improve response times for younger adults for visual tasks relevant to driving.

Assessment of neuroretinal function in a group of functional amblyopes with documented LGN deficits

Purpose In this study we examine neuroretinal function in five amblyopes, who had been shown in previous functional MRI (fMRI) studies to have compromised function of the lateral geniculate nucleus (LGN), to determine if the fMRI deficit in amblyopia may have its origin at the retinal level. Methods We used slow flash multifocal ERG (mfERG) and compared averaged five ring responses of the amblyopic and fellow eyes across a 35 deg field. Central responses were also assessed over a field which was about 6.3 deg in diameter. We measured central retinal thickness using optical coherence tomography. Central fields were measured using the MP1-Microperimeter which also assesses ocular fixation during perimetry. MfERG data were compared with fMRI results from a previous study. Results Amblyopic eyes had reduced response density amplitudes (first major negative to first positive (N1-P1) responses) for the central and paracentral retina (up to 18 deg diameter) but not for the mid-periphery (from 18 to 35 deg). Retinal thickness was within normal limits for all eyes, and not different between amblyopic and fellow eyes. Fixation was maintained within the central 4° more than 80% of the time by four of the five participants; fixation assessed using bivariate contour ellipse areas (BCEA) gave rankings similar to those of the MP-1 system. There was no significant relationship between BCEA and mfERG response for either amblyopic or fellow eye. There was no significant relationship between the central mfERG eye response difference and the selective blood oxygen level dependent (BOLD) LGN eye response difference previously seen in these participants. Conclusions Retinal responses in amblyopes can be reduced within the central field without an obvious anatomical basis. Additionally, this retinal deficit may not be the reason why the LGN BOLD (blood oxygen level dependent) responses are reduced for amblyopic eye stimulation.

Temporal summation of intrinsically photosensitive retinal ganglion cell (ipRGC) contributions to the human pupil.

Purpose: IpRGCs mediate non-image forming functions including photoentrainment and the pupil light reflex (PLR). Temporal summation increases visual sensitivity and decreases temporal resolution for image forming vision, but the summation properties of nonimage forming vision are unknown. We investigated the temporal summation of inner (ipRGC) and outer (rod/cone) retinal inputs to the PLR. Method: The consensual PLR of the left eye was measured in six participants with normal vision using a Maxwellian view infrared pupillometer. Temporal summation was investigated using a double-pulse protocol (100 ms stimulus pairs; 0–1024 ms inter-stimulus interval, ISI) presented to the dilated fellow right eye (Tropicamide 1%). Stimulus lights (blue λmax = 460 nm; red λmax = 638 nm) biased activity to inneror outer retinal inputs to non-image forming vision. Temporal summation was measured suprathreshold (15.2 log photons.cm−2.s−1 at the cornea) and subthreshold (11.4 log photons.cm−2.s−1 at the cornea). Results: RM-ANOVAs showed the suprathreshold and subthreshold 6 second post illumination pupil response (PIPR: expressed as percentage baseline diameter) did not significantly vary for red or blue stimuli (p > .05). The PIPR for a subthreshold red 16 ms double-pulse control condition did not significantly differ with ISI (p > .05). The maximum constriction amplitude for red and blue 100 ms double- pulse stimuli did not significantly vary with ISI (p > .05). Conclusion: The non-significant changes in suprathreshold PIPR and subthreshold maximum pupil constriction indicate that inner retinal ipRGC inputs and outer retinal photoreceptor inputs to the PLR do not show temporal summation. The results suggest a fundamental difference between the temporal summation characteristics of image forming and non-image forming vision.

Eyes on 3D-Current 3D biomimetic disease concept models and potential applications in age-related macular degeneration

Three dimensional cellular models that mimic disease are being increasingly investigated and have opened an exciting new research area into understanding pathomechanisms. The advantage of 3D in vitro disease models is that they allow systematic and in-depth studies of physiological and pathophysiological processes with less costs and ethical concerns that have arisen with animal models. The purpose of the 3D approach is to allow crosstalk between cells and microenvironment, and with cues from the microenvironment, cells can assemble their niche similar to in vivo conditions. The use of 3D models for mimicking disease processes such as cancer, osteoarthritis etc., is only emerging and allows multidisciplinary teams consisting of tissue engineers, biologist biomaterial scientists and clinicians to work closely together. While in vitro systems require rigorous testing before they can be considered as replicates of the in vivo model, major steps have been made, suggesting that they will become powerful tools for studying physiological and pathophysiological processes. This paper aims to summarize some of the existing 3D models and proposes a novel 3D model of the eye structures that are involved in the most common cause of blindness in the Western World, namely age-related macular degeneration (AMD).

Gradients of refractive index in the crystalline lens and transient changes in refraction among patients with diabetes

Transient hyperopic refractive shifts occur on a timescale of weeks in some patients after initiation of therapy for hyperglycemia, and are usually followed by recovery to the original refraction. Possible lenticular origin of these changes is considered in terms of a paraxial gradient index model. Assuming that the lens thickness and curvatures remain unchanged, as observed in practice, it appears possible to account for initial hyperopic refractive shifts of up to a few diopters by reduction in refractive index near the lens center and alteration in the rate of change between center and surface, so that most of the index change occurs closer to the lens surface. Restoration of the original refraction depends on further change in the refractive index distribution with more gradual changes in refractive index from the lens center to its surface. Modeling limitations are discussed.

Translating vision research into policy and practice to improve visibility, and hence safety, of road workers at night

This case study report describes the stages involved in the translation of research on night-time visibility into standards for the safety clothing worn by roadworkers. Vision research demonstrates that when lights are placed on the moveable joints of the body and the person moves in a dark setting, the phenomenon known as “biological motion or biomotion” occurs, enabling rapid and accurate recognition of the human form although only the lights can be seen. QUT was successful in gaining funding from the Australian Research Council for a Linkage grant due to the support of the predecessors of the Queensland Department of Transport and Main Roads (TMR) to research the biomotion effect in on-road settings using materials that feature in roadworker clothing. Although positive results were gained, the process of translating the research results into policy, practices and standards relied strongly on the supportive efforts of TMR staff engaged in the review and promulgation of national standards. The ultimate result was the incorporation of biomotion marking into AS/NZS 4602.1 2011. The experiences gained in this case provide insights into the processes involved in translating research into practice.

Diurnal variation of ocular biometrics under natural and defocused conditions

It is well known that a broad range of ocular anatomical and physiological parameters undergo significant diurnal variation. However, the natural diurnal variations that occur in the length of the human eye (axial length) and their underlying causes have been less well studied. Improvements in optical methods for the measurement of ocular biometrics now allow more precise and comprehensive measurements of axial length to be performed than has previously been possible. Research from animal models also suggests a link between diurnal axial length variations and longer term myopic eye growth, and that retinal image defocus can disrupt these diurnal rhythms in axial length. This research programme has examined the diurnal variations in axial length in young normal eyes, the contributing components and the influence of optical stimuli on these changes. In the first experiment, the normal pattern and consistency of the diurnal variations in axial length were examined at 10 different times (5 measurements each day, at ~ 3-hour intervals from ~ 9 am to ~ 9 pm) over 2 consecutive days on 30 young adult subjects (15 myopes, 15 emmetropes). Additionally, variations in a range of other ocular biometric measurements such as choroidal thickness, intraocular pressure, and other ocular biometrics were also explored as potential factors that may be associated with the observed variations in axial length. To investigate the potential influence of refractive error on diurnal axial length variations, the differences in the magnitude and pattern of diurnal variations in axial length between the myopic and emmetropic subjects were examined. Axial length underwent significant diurnal variation that was consistently observed over the 2 consecutive days of measurements, with the longest axial length typically occurring during the day, and the shortest at night. Significant diurnal variations were also observed in choroidal thickness, IOP and other ocular biometrics (such as central corneal thickness, anterior chamber depth and vitreous chamber depth) of the eye. Diurnal variations in vitreous chamber depth, IOP (positive associations) and choroidal thickness (negative association) were all significantly correlated with the diurnal changes in axial length. Choroidal thickness was found to fluctuate approximately in antiphase to the axial length changes, with the average timing of the longest axial length coinciding with the thinnest choroid and vice versa. There were no significant differences in the ocular diurnal variations associated with refractive error. Given that the diurnal changes in axial length could be associated with the changes in the eye’s optical quality, whether the optical quality of the eye also undergoes diurnal variation in the same cohort of young adult myopes and emmetropes over 2 consecutive days was also examined. Significant diurnal variations were observed only in the best sphere refraction (power vector M) and in the spherical aberration of the eye over two consecutive days of testing. The changes in the eyes lower and higher order ocular optics were not significantly associated with the diurnal variations in axial length and the other measured ocular biometric parameters. No significant differences were observed in the magnitude and timing of diurnal variations in lower-order and higher-order optics associated with refractive error. Since the small natural fluctuations in the eye’s optical quality did not appear to be sufficient to influence the natural diurnal fluctuations in ocular biometric parameters, in the next experiment, the influence of monocular myopic defocus (+1.50 DS) upon the normal diurnal variations in axial length and choroidal thickness of young adult emmetropic human subjects (n=13) imposed over a 12 hour period was examined. A series of axial length and choroidal thickness measurements (collected at ~3 hourly intervals, with the first measurement at ~9 am and the final measurement at ~9 pm) were obtained over three consecutive days. The natural diurnal rhythms (Day 1, no defocus), diurnal rhythms with monocular myopic defocus (Day 2, +1.50 DS spectacle lens over the right eye), and the recovery from any defocus induced changes (Day 3, no defocus) were examined. Significant diurnal variations over the course of the day were observed in both axial length and choroidal thickness on each of the three measurement days. The introduction of monocular myopic defocus led to significant reductions in the mean amplitude of diurnal change, and phase shifts in the peak timing of the diurnal rhythms in axial length and choroidal thickness. These defocus induced changes were found to be transient in nature and returned to normal the day following removal of the defocus. To further investigate the influence of optical stimuli on human diurnal rhythms, in the final experiment, the influence of monocular hyperopic defocus on the normal diurnal rhythms in axial length and choroidal thickness was examined in young adult emmetropic subjects (n=15). Similar to the previous experiment, the natural diurnal rhythms (Day 1, no defocus), diurnal rhythms with monocular hyperopic defocus (Day 2, -2.00 DS spectacle lens over the right eye), and the recovery from any defocus induced changes (Day 3, no defocus) were examined over three consecutive days. Both axial length and choroidal thickness underwent significant diurnal variations on each of the three days. The introduction of monocular hyperopic defocus resulted in a significant increase in the amplitude of diurnal change, but no change in the peak timing of diurnal rhythms in both parameters. The ocular changes associated with hyperopic defocus returned to normal, the day following removal of the defocus. This research has shown that axial length undergoes significant diurnal variation in young adult human eyes, and has shown that the natural diurnal variations in choroidal thickness and IOP are significantly associated, and may underlie these diurnal fluctuations in axial length. This work also demonstrated for the first time that exposing young human eyes to monocular myopic and hyperopic defocus leads to a significant disruption in the normal diurnal rhythms of axial length and choroidal thickness. These changes in axial length with defocus may reflect underlying mechanisms in the human eye that are involved in the regulation of longer term eye growth.