Neonatal Hypoglycemia and Neurocognitive Function at School Age: A Prospective Cohort Study.

OBJECTIVE: To determine the relationship between transient neonatal hypoglycemia in at-risk infants and neurocognitive function at 6-7 years of corrected age. STUDY DESIGN: The pre-hPOD Study involved children born with at least 1 risk factor for neonatal hypoglycemia. Hypoglycemia was defined as ≥1 consecutive blood glucose concentrations <47 mg/dl (2.6 mmol/L), severe as <36 mg/dl (2.0 mmol/L), mild as 36 to <47 mg/dL (2.0 to <2.6 mmol/L), brief as 1-2 episodes, and recurrent as ≥3 episodes. At 6-7 years children were assessed for cognitive and motor function (NIH-Toolbox), learning, visual perception and behavior. The primary outcome was neurocognitive impairment, defined as >1 SD below the normative mean in ≥1 Toolbox tests. The 8 secondary outcomes covered children's cognitive, motor, language, emotional-behavioral, and visual perceptual development. Primary and secondary outcomes were compared between children who did and did not experience neonatal hypoglycemia, adjusting for potential confounding by gestation, birthweight, sex and receipt of prophylactic dextrose gel (pre-hPOD intervention). Secondary analysis included assessment by severity and frequency of hypoglycemia. RESULTS: Of 392 eligible children, 315 (80%) were assessed at school age (primary outcome, n = 308); 47% experienced hypoglycemia. Neurocognitive impairment was similar between exposure groups (hypoglycemia 51% vs 50% no hypoglycemia; aRD -4%, 95% CI -15%, 7%). Children with severe or recurrent hypoglycemia had worse visual motion perception and increased risk of emotional-behavioral difficulty. CONCLUSION: Exposure to neonatal hypoglycemia was not associated with risk of neurocognitive impairment at school-age in at-risk infants, but severe and recurrent episodes may have adverse impacts. TRIAL REGISTRATION: Hypoglycemia Prevention in Newborns with Oral Dextrose: the Dosage Trial (pre-hPOD Study): ACTRN12613000322730.

Dextrose gel prophylaxis for neonatal hypoglycaemia and neurocognitive function at early school age: a randomised dosage trial.

OBJECTIVE: To investigate the effect of different doses of prophylactic dextrose gel on neurocognitive function and health at 6-7 years. DESIGN: Early school-age follow-up of the pre-hPOD (hypoglycaemia Prevention with Oral Dextrose) study. SETTING: Schools and communities. PATIENTS: Children born at ≥35 weeks with ≥1 risk factor for neonatal hypoglycaemia: maternal diabetes, small or large for gestational age, or late preterm. INTERVENTIONS: Four interventions commencing at 1 hour of age: dextrose gel (40%) 200 mg/kg; 400 mg/kg; 200 mg/kg and 200 mg/kg repeated before three feeds (800 mg/kg); 400 mg/kg and 200 mg/kg before three feeds (1000 mg/kg); compared with equivolume placebo (combined for analysis). MAIN OUTCOMES MEASURES: Toolbox cognitive and motor batteries, as well as tests of motion perception, numeracy and cardiometabolic health, were used. The primary outcome was neurocognitive impairment, defined as a standard score of more than 1 SD below the age-corrected mean on one or more Toolbox tests. FINDINGS: Of 392 eligible children, 309 were assessed for the primary outcome. There were no significant differences in the rate of neurocognitive impairment between those randomised to placebo (56%) and dextrose gel (200 mg/kg 46%: adjusted risk difference (aRD)=-14%, 95% CI -35%, 7%; 400 mg/kg 48%: aRD=-7%, 95% CI -27%, 12%; 800 mg/kg 45%: aRD=-14%, 95% CI -36%, 9%; 1000 mg/kg 50%: aRD=-8%, 95% CI -29%, 13%). Children exposed to any dose of dextrose gel (combined), compared with placebo, had a lower risk of motor impairment (3% vs 14%, aRD=-11%, 95% CI -19%, -3%) and higher mean (SD) cognitive scores (106.0 (15.3) vs 101.1 (15.7), adjusted mean difference=5.4, 95% CI 1.8, 8.9). CONCLUSIONS: Prophylactic neonatal dextrose gel did not alter neurocognitive impairment at early school age but may have motor and cognitive benefits. Further school-age follow-up studies are needed.

OKN-Fast: Objective visual acuity threshold measurement using the optokinetic response.

Visual acuity (VA) is the gold-standard measure for the assessment of visual function, but it is challenging to obtain in non-verbal adults and young children. We present OKN-Fast, an objective, automated method for estimation of VA using a reflexive eye movement called optokinetic nystagmus (OKN) that does not require a verbal response from the patient (VA-OKN). We tested the method in a cohort of healthy adults (n=12) with good vision, who were also blurred using a lens. On average OKN-Fast reduced the number of trials needed to determine threshold by half, as compared to a gold standard trial-by-trial assessment. The VAs determined by OKN and ETDRS were similar when blurred (no statistically significant difference). However, a significant bias of logMAR 0.2 was observed for the good vision condition. VA-OKN was highly repeatable with limits of agreement (LOA) similar to those found for ETDRS charts when blurred. However, this VA-OKN was only moderately correlated with VA measured using a ETDRS chart (r2 = 0.55). These results suggest that further optimization is warranted.Clinical Relevance- This work provides an automated approach for the estimation of visual acuity in non-verbal populations such as young children or non-verbal adults.

Measuring aniseikonia and investigating neuroplasticity and image factors in amblyopia (MAGNIFY): study protocol for a randomised clinical trial.

BACKGROUND: Aniseikonia represents a potential barrier to neuroplasticity which may limit visual outcomes in children with anisometropic amblyopia. Full correction of refractive error is the first step in standard amblyopia treatment, which corrects for image focus but neglects image size differences. METHODS: The MAGNIFY study is a double-masked, randomised clinical trial investigating the effectiveness of aniseikonia correcting lenses in children at first diagnosis of significant anisometropia. We hypothesis that aniseikonia correction lenses will improve image clarity and reduce the retinal size differences producing better visual acuity and stereoacuity improvements after 15 weeks of optical treatment for children with anisometropia. Eligible children will be randomly allocated to the treatment group (aniseikonia-correcting spectacle lenses) or control group (standard spectacle lenses). Visual acuity and binocular functions will be assessed every 5 weeks during the 15-week optical treatment phase according to standard amblyopia treatment protocol. DISCUSSION: It is possible that correcting aniseikonia along with anisometropia at first diagnosis will promote binocularity as well as increase spectacle adherence by reducing visual discomfort, improving optical treatment outcomes. This could then reduce the need for additional amblyopia treatment such as patching or atropine, reducing the burden on hospital eye departments and potentially improving visual outcomes for children with amblyopia. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000061932 . Registered on 24 January 2020. Protocol 15th November 2019, version one.

Association of Neonatal Hypoglycemia With Academic Performance in Mid-Childhood.

Importance: Neonatal hypoglycemia is associated with increased risk of poor executive and visual-motor function, but implications for later learning are uncertain. Objective: To test the hypothesis that neonatal hypoglycemia is associated with educational performance at age 9 to 10 years. Design, Setting, and Participants: Prospective cohort study of moderate to late preterm and term infants born at risk of hypoglycemia. Blood and masked interstitial sensor glucose concentrations were measured for up to 7 days. Infants with hypoglycemic episodes (blood glucose concentration <47 mg/dL [2.6 mmol/L]) were treated to maintain a blood glucose concentration of at least 47 mg/dL. Six hundred fourteen infants were recruited at Waikato Hospital, Hamilton, New Zealand, in 2006-2010; 480 were assessed at age 9 to 10 years in 2016-2020. Exposures: Hypoglycemia was defined as at least 1 hypoglycemic event, representing the sum of nonconcurrent hypoglycemic and interstitial episodes (sensor glucose concentration <47 mg/dL for ≥10 minutes) more than 20 minutes apart. Main Outcomes and Measures: The primary outcome was low educational achievement, defined as performing below or well below the normative curriculum level in standardized tests of reading comprehension or mathematics. There were 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health. Results: Of 587 eligible children (230 [48%] female), 480 (82%) were assessed at a mean age of 9.4 (SD, 0.3) years. Children who were and were not exposed to neonatal hypoglycemia did not significantly differ on rates of low educational achievement (138/304 [47%] vs 82/176 [48%], respectively; adjusted risk difference, -2% [95% CI, -11% to 8%]; adjusted relative risk, 0.95 [95% CI, 0.78-1.15]). Children who were exposed to neonatal hypoglycemia, compared with those not exposed, were significantly less likely to be rated by teachers as being below or well below the curriculum level for reading (68/281 [24%] vs 49/157 [31%], respectively; adjusted risk difference, -9% [95% CI, -17% to -1%]; adjusted relative risk, 0.72 [95% CI, 0.53-0.99; P = .04]). Groups were not significantly different for other secondary end points. Conclusions and Relevance: Among participants at risk of neonatal hypoglycemia who were screened and treated if needed, exposure to neonatal hypoglycemia compared with no such exposure was not significantly associated with lower educational achievement in mid-childhood.

Clinical Aniseikonia in Anisometropia and Amblyopia.

PURPOSE: Clinically, aniseikonia (a perceived difference in shape and image size between the eyes) is often neglected in anisometropic amblyopia due to assumed measurement difficulties. Therefore, we currently lack evidence on whether correction of aniseikonia is beneficial. This study aimed to determine whether subjective aniseikonia is measurable in anisometropia with or without amblyopia. METHODS: Participants (15-52 years) with Anisometropic Amblyopia (n = 7), Anisometropia without amblyopia (n = 6) and Isometropic Controls (n = 6) were recruited. Subjective aniseikonia was measured using three clinical techniques: Robertson Technique (RT) (penlight and Maddox rod), Aniseikonia Inspector Version 3 (AI3), and the New Aniseikonia Test booklet (NAT), and a psychophysical adaptive method, the Contrast-balanced Aniseikonia Test (CAT), where dichoptic contrast adjustments compensate for any suppression. RESULTS: Eighteen participants completed all tests, one Anisometropic Amblyopia participant could only complete the CAT and NAT due to fusion loss. The Anisometropic Amblyopia group exhibited the most aniseikonia (range -1.50-+10.50%) followed by Anisometropic Controls (range -3.30-+4.50%) and Isometropic Controls (range -1.50-+3.28%). There was a significant trend of more subjective aniseikonia with increasing amounts of anisometropia across all four tests (AI3 r = 0.630, p = 0.005; NAT r = 0.542, p = 0.017; RT r = 0.499, p = 0.035; CAT r = 0.440, p = 0.059. Bland Altman analysis demonstrated clinically significant levels of variability between the tests. CONCLUSIONS: Subjective aniseikonia can be reliably measured in patients with anisometropia and suppression. Subjective aniseikonia measurement is recommended as four of the most commonly used clinical tests did not support the 1% per dioptre rule of thumb.

Aniseikonia and anisometropia: implications for suppression and amblyopia.

Aniseikonia is a difference in the perceived size or shape of images between eyes, and can arise from a variety of physiological, neurological, retinal, and optical causes. Aniseikonia is associated with anisometropia, as both anisometropia itself and the optical correction for anisometropia can cause aniseikonia. Image size differences above one to three per cent can be clinically symptomatic. Common symptoms include asthenopia, headache and diplopia in vertical gaze. Size differences of three and more impair binocular visual functions such as binocular summation and stereopsis. Above five per cent of aniseikonia, binocular inhibition or suppression tend to occur to prevent diplopia and confusion. Aniseikonia can be measured using a range of techniques and can be corrected or reduced by prescribing contact lenses or specially designed spectacle lenses. Subjective testing of aniseikonia is the only way to accurately measure the overall perceived amount of aniseikonia. However, currently it is not routinely assessed in most clinical settings. At least two-thirds of patients with amblyopia have anisometropia, thus we may expect aniseikonia to be common in patients with anisometropic amblyopia. However, aniseikonia may not be experienced by the patient under normal binocular viewing conditions if the image from the amblyopic eye is of poor quality or is too strongly suppressed for image size differences to be recognised. This lack of binocular simultaneous perception in amblyopia may also prevent the measurement of aniseikonia, as most common techniques require direct comparisons of images seen by each eye. Current guidelines for the treatment of amblyopia advocate full correction of anisometropia to equalise image clarity, but do not address aniseikonia. Significant image size differences between eyes may lead to suppression and abnormal binocular adaptations. It is possible that correcting anisometropia and aniseikonia simultaneously, particularly at the initial diagnosis of anisometropia, would reduce the need to develop suppression and improve treatment outcomes for anisometropic amblyopia.

Caffeine increases the velocity of rapid eye movements in unfatigued humans.

BACKGROUND: Caffeine is a widely used dietary stimulant that can reverse the effects of fatigue on cognitive, motor and oculomotor function. However, few studies have examined the effect of caffeine on the oculomotor system when homeostasis has not been disrupted by physical fatigue. This study examined the influence of a moderate dose of caffeine on oculomotor control and visual perception in participants who were not fatigued. METHODS: Within a placebo-controlled crossover design, 13 healthy adults ingested caffeine (5 mg·kg-1 body mass) and were tested over 3 h. Eye movements, including saccades, smooth pursuit and optokinetic nystagmus, were measured using infrared oculography. RESULTS: Caffeine was associated with higher peak saccade velocities (472 ± 60° s-1) compared to placebo (455 ± 62° s-1). Quick phases of optokinetic nystagmus were also significantly faster with caffeine, whereas pursuit eye movements were unchanged. Non-oculomotor perceptual tasks (global motion and global orientation processing) were unaffected by caffeine. CONCLUSIONS: These results show that oculomotor control is modulated by a moderate dose of caffeine in unfatigued humans. These effects are detectable in the kinematics of rapid eye movements, whereas pursuit eye movements and visual perception are unaffected. Oculomotor functions may be sensitive to changes in central catecholamines mediated via caffeine's action as an adenosine antagonist, even when participants are not fatigued.

Effects of Dopamine and Norepinephrine on Exercise-induced Oculomotor Fatigue.

INTRODUCTION: Fatigue-induced impairments in the control of eye movements are detectable via reduced eye movement velocity after a bout of prolonged, strenuous exercise. Slower eye movements caused by neural fatigue within the oculomotor system can be prevented by caffeine, and the upregulation of central catecholamines may be responsible for this effect. This study explored the individual contribution of dopamine and norepinephrine to fatigue-related impairments in oculomotor control. METHODS: The influence of a dopamine reuptake inhibitor (methylphenidate) and a norepinephrine reuptake inhibitor (reboxetine) was assessed in 12 cyclists performing 180 min of stationary cycling within a placebo-controlled crossover design. Eye movement kinematics (saccades, smooth pursuit, and optokinetic nystagmus) were measured using infrared oculography. Visual attention was assessed with overt and covert spatial attention tasks. RESULTS: Exercise-induced fatigue was associated with a 6% ± 8% reduction in the peak velocity of visually guided, reflexive prosaccades. Importantly, both dopamine reuptake inhibition and norepinephrine reuptake inhibition prevented fatigue-related decrements in the peak velocity of prosaccades. Pursuit eye movements, optokinetic nystagmus, and visual attention tasks were unaffected by exercise or drug treatments. CONCLUSION: Overall, our findings suggest that alterations in norepinephrinergic and dopaminergic neurotransmission are linked with the development of fatigue within circuits that control eye movements. Psychiatric medications that target central catecholamines can exert a protective effect on eye movements after prolonged exercise.

Infrared Video Pupillography Coupled with Smart Phone LED for Measurement of Pupillary Light Reflex.

Clinical assessment of pupil appearance and pupillary light reflex (PLR) may inform us the integrity of the autonomic nervous system (ANS). Current clinical pupil assessment is limited to qualitative examination, and relies on clinical judgment. Infrared (IR) video pupillography combined with image processing software offer the possibility of recording quantitative parameters. In this study we describe an IR video pupillography set-up intended for human and animal testing. As part of the validation, resting pupil diameter was measured in human subjects using the NeurOptics™ (Irvine, CA, USA) pupillometer, to compare against that measured by our IR video pupillography set-up, and PLR was assessed in guinea pigs. The set-up consisted of a smart phone with a light emitting diode (LED) strobe light (0.2 s light ON, 5 s light OFF cycles) as the stimulus and an IR camera to record pupil kinetics. The consensual response was recorded, and the video recording was processed using a custom MATLAB program. The parameters assessed were resting pupil diameter (D1), constriction velocity (CV), percentage constriction ratio, re-dilation velocity (DV) and percentage re-dilation ratio. We report that the IR video pupillography set-up provided comparable results as the NeurOptics™ pupillometer in human subjects, and was able to detect larger resting pupil size in juvenile male guinea pigs compared to juvenile female guinea pigs. At juvenile age, male guinea pigs also had stronger pupil kinetics for both pupil constriction and dilation. Furthermore, our IR video pupillography set-up was able to detect an age-specific increase in pupil diameter (female guinea pigs only) and reduction in CV (male and female guinea pigs) as animals developed from juvenile (3 months) to adult age (7 months). This technique demonstrated accurate and quantitative assessment of pupil parameters, and may provide the foundation for further development of an integrated system useful for clinical applications.

Fatigue-related impairments in oculomotor control are prevented by norepinephrine-dopamine reuptake inhibition.

Fatigue-induced reductions in saccade velocity have been reported following acute, prolonged exercise. Interestingly, the detrimental impact of fatigue on oculomotor control can be prevented by a moderate dose of caffeine. This effect may be related to central catecholamine upregulation via caffeine's action as an adenosine antagonist. To test this hypothesis, we compared the protective effect of caffeine on oculomotor control post-exercise to that of a norepinephrine-dopamine reuptake inhibitor. Within a placebo-controlled crossover design, 12 cyclists consumed placebo, caffeine or a norepinephrine-dopamine reuptake inhibitor (bupropion) during 180 minutes of stationary cycling. Saccades, smooth pursuit and optokinetic nystagmus were measured using infrared oculography. Exercise fatigue was associated with an 8 ± 11% reduction in the peak velocity of prosaccades, and a 10 ± 11% decrement in antisaccade peak velocity. Optokinetic nystagmus quick phases decreased in velocity by 15 ± 17%. These differences were statistically significant (p < 0.05). Norepinephrine-dopamine reuptake inhibition and caffeine prevented fatigue-related decrements in eye movement velocity. Pursuit eye movements and visual attention were unaffected. These findings show that norepinephrine-dopamine reuptake inhibition protects oculomotor function during exercise fatigue. Caffeine's fatigue-reversing effects on eye movements appear to be mediated, at least in part, via modulation of central catecholamines.

Quantitative Analysis of Corneal Energy Dissipation and Corneal and Orbital Deformation in Response to an Air-Pulse in Healthy Eyes.

PURPOSE: To examine and evaluate ocular biomechanical metrics and additionally derived corneal and orbital components using a noncontact Scheimpflug-based tonometer (CorVis ST) in a population of healthy eyes. METHODS: A total of 152 eyes of 152 participants were examined by slit-lamp biomicroscopy, corneal tomography, and the CorVis ST (CST). This determined the distribution of outputs from the CST, such as deformation amplitude (DA), and additionally derived parameters, including maximum corneal deformation (MCD), maximum orbital deformation (MOD), and corneal energy dissipation (CED). RESULTS: The mean age of participants was 35.88 ± 13.8 years. Deformation amplitude significantly correlated with age (r = 0.24, P = 0.002) but not sex or ethnicity (P > 0.05). Multiple linear regression analysis revealed significant correlations between DA and age (r = 0.19, P = 0.006) and DA and IOP (r = -0.59, P < 0.001). Age correlated with MCD (r = 0.20, P = 0.01), MOD (r = 0.18, P = 0.03), and CED (r = 0.39, P < 0.001). Males had a lower MOD than females (0.24 vs. 0.26 mm, respectively, P = 0.01); however, there were no differences in MCD or CED between sexes (P > 0.05). There were no significant differences between ethnicities for MCD, MOD, and CED (P > 0.05). Multiple linear regression analysis revealed significant correlations between MCD and IOP (r = -0.65, P < 0.001), CED and age (r = 0.41, P < 0.001), CED and IOP (r = 0.28, P = 0.001), and between CED and central corneal thickness (CCT) (r = -0.36, P < 0.001). CONCLUSIONS: The isolation of the corneal component (MCD) should be used when analyzing deformation characteristics in diseases that only affect the cornea. This study establishes a baseline for a population of healthy eyes. Future publications will identify differences in MCD, MOD, and CED between healthy and diseased populations.

An Optokinetic Nystagmus Detection Method for Use With Young Children.

The detection of vision problems in early childhood can prevent neurodevelopmental disorders such as amblyopia. However, accurate clinical assessment of visual function in young children is challenging. optokinetic nystagmus (OKN) is a reflexive sawtooth motion of the eye that occurs in response to drifting stimuli, that may allow for objective measurement of visual function in young children if appropriate child-friendly eye tracking techniques are available. In this paper, we present offline tools to detect the presence and direction of the optokinetic reflex in children using consumer grade video equipment. Our methods are tested on video footage of children ([Formula: see text] children and 20 trials) taken as they freely observed visual stimuli that induced horizontal OKN. Using results from an experienced observer as a baseline, we found the sensitivity and specificity of our OKN detection method to be 89.13% and 98.54%, respectively, across all trials. Our OKN detection results also compared well (85%) with results obtained from a clinically trained assessor. In conclusion, our results suggest that OKN presence and direction can be measured objectively in children using consumer grade equipment, and readily implementable algorithms.

A method for detecting optokinetic nystagmus based on the optic flow of the limbus.

Optokinetic nystagmus (OKN) is the sawtooth movement of the eye elicited when an observer views a repeated moving pattern. We present a method for identifying the presence and direction of OKN in recordings of the eye made using a standard off-the-shelf video-camera or webcam. Our approach uses vertical edge detection to determine the limbus/iris boundary, and we estimate the velocity of the edge using Lucas-Kanade optical flow. Heuristic rules are applied to identify saccadic velocity peaks from the resulting velocity signal. The normalized average of the resulting peaks is used to estimate the presence/direction of OKN. Our preliminary testing with six participants observing global motion stimuli with full or partial coherence yields an accuracy of 93% which compares favorably to the performance of an experienced human observer (98% accuracy). Additional tests using high contrast, square-wave gratings show that performance of the technique is consistent at stimulus speeds of 5 and 10deg/s and that OKN is not reported by the algorithm when participants view stationary stimuli.

Fully automated montaging of laser scanning in vivo confocal microscopy images of the human corneal subbasal nerve plexus.

PURPOSE: Creating wide-field montages of the human corneal subbasal nerve plexus using laser scanning in vivo confocal microscopy (IVCM) requires considerable expertise and remains highly labor intensive. A typical montage contains several hundred images to be quality checked and manually arranged. The purpose of this study was to develop and validate software for off-line montaging of IVCM images of the living human cornea. METHODS: The software was developed and tested using four large data sets of IVCM images from normal human corneas. Two of the data sets were used for calibration purposes, the remaining images served as a validation set. Techniques utilized included image binarization, clustering, key-point generation, and feature-based stitching. A range of tests involving computer processing and visual inspection were applied to audit and compare the automated montages with manually constructed montages. RESULTS: The original IVCM images (N = 2565) from four corneas were processed into image groups, reducing the number of effective images by 68% to 86%. Each data set contained a large primary grouping. A clustering strategy was used to reduce the total potential workload by 57%. Both programmatic and visual inspection confirmed the method was robust to errors, with a specificity of 100% (i.e., no falsely matched images). The time taken to complete the montage varied from 1.5 to 3 hours. METHODS: Computer-driven image stitching is a useful, effective, and time-saving tool for studies involving IVCM corneal nerve imaging. Further research will extend and optimize these

Effects of illumination and observation angle on the van Herick procedure.

BACKGROUND: This study reports how illumination and observation angles affect assessments of the openness of the anterior chamber angle using the van Herick technique. METHODS: The angle of the tangent to the corneal surface at the temporal limbus was measured for 50 participants. The effect on anterior chamber depth to corneal thickness (AC:C) ratio of varying the illumination angle away from the perpendicular to this tangent was measured. The effect of varying observation angle was also evaluated. An optical model was constructed to simulate the parameters likely to affect measurement of the AC:C ratio. RESULTS: The average angle of the tangent to the corneal surface at the temporal limbus was 43.1 ± 5.4° (SD). With illumination perpendicular to the limbal-corneal surface, varying the observation angle caused clinically unimportant (less than 0.1 ratio difference) but statistically significant changes in AC:C ratios (F = 7.235, p < 0.0001; repeated measures ANOVA). With observation 60° away from illumination, varying the illumination angle away from the perpendicular to the limbal-corneal surface caused clinically important and statistically significant changes in AC:C ratios (F = 75.981, p < 0.0001; repeated measures ANOVA). The optical model confirmed the experimental results and predicts that the conclusions are applicable outside our study population. CONCLUSIONS: Illumination should be within 10° either side of the perpendicular to the corneal surface at the limbus for measurements of the AC:C ratio. The observation angle away from the illumination direction is not critical and 60° is appropriate, but smaller angles can be used.

Eye for modeling visual distortion in central serous retinopathy.

PURPOSE: To present a simple mathematical eye model capable of modeling the metamorphopsia (visual distortion) reported by patients with central serous retinopathy (CSR). METHODS: A computer program was developed to perform the modeling. A simple wide-angle eye model was adapted to include a spherical edema added at the retina. The visual impression was taken as the projection of the retinal pattern back into object space, after the edema had been deflated to its undistorted state. The deflation of the edema was facilitated by assuming a simplified "spreading of photoreceptors" rule. Numerical examples have been included to demonstrate the use of the model. In particular, an Amsler grid was projected to the retina with CSR, to illustrate the associated geometrical distortion. RESULTS: The eye model predicted a pincushion-like distortion of an Amsler grid, that depended (for given height) on the radius of curvature of the CSR. A larger radius of curvature resulted in less pincushion distortion extending over a larger area. CONCLUSIONS: An eye model has been developed that simulates distortion because of CSR. The predicted visual impression of a spherical edema is a pincushion-like distortion. This model may have applications in benchmarking alternate chart designs for detecting CSR, investigating optical aberrations over the edema as well as simulating the visual effect of metamorphopsia in other retinal conditions.

Diagnosing dry eye with dynamic-area high-speed videokeratoscopy.

Dry eye syndrome is one of the most commonly reported eye health conditions. Dynamic-area high-speed videokeratoscopy (DA-HSV) represents a promising alternative to the most invasive clinical methods for the assessment of the tear film surface quality (TFSQ), particularly as Placido-disk videokeratoscopy is both relatively inexpensive and widely used for corneal topography assessment. Hence, improving this technique to diagnose dry eye is of clinical significance and the aim of this work. First, a novel ray-tracing model is proposed that simulates the formation of a Placido image. This model shows the relationship between tear film topography changes and the obtained Placido image and serves as a benchmark for the assessment of indicators of the ring's regularity. Further, a novel block-feature TFSQ indicator is proposed for detecting dry eye from a series of DA-HSV measurements. The results of the new indicator evaluated on data from a retrospective clinical study, which contains 22 normal and 12 dry eyes, have shown a substantial improvement of the proposed technique to discriminate dry eye from normal tear film subjects. The best discrimination was obtained under suppressed blinking conditions. In conclusion, this work highlights the potential of the DA-HSV as a clinical tool to diagnose dry eye syndrome.

Reconstructing ocular surfaces by Purkinje images using an exact ray approach: estimating IOL decenter and tilt.

Recently, an alternate method for recovering the shape of the anterior surface of an intraocular lens (IOL) (by Purkinje images), and capable of returning a Zernike polynomial representation of that surface, was proposed (Ophthal. Physiol Opt., 29, 2009, 80-91). However, in moving toward a clinically applicable method, it is important to estimate parameters such as surface radius, lens tilt and decenter. Previously, radius of curvature (for the anterior surface of an IOL) was estimated by finding the best-fit sphere. A methodology is presented here to recover lens tilt and decenter using this alternate method. The theory is developed and then tested in simulation. An IOL is added to the Navarro eye, and then recovered by assuming: (i) the same 'full eye', and (ii) a reduced two surface version (the 'simplified' eye). A number of decenter and tilt settings are tested, from which root mean squared (RMS) surface errors, best-fit spheres, tilt and decenter values are estimated. Mis-measurement of the axial position of the posterior surface of the IOL is also simulated. The full eye model produces low RMS surface and radii of curvature errors, that increase linearly with axial shift. The error behaviour is not greatly affected by changes in IOL decenter and/or tilt. The simplified eye (n = 1.32 for aqueous) with n = 1.4760 (at lambda = 880 nm) for the IOL, fits the 'full eye' results most consistently. Lens decenter is consistently estimated to within 0.015 mm (for a 1 mm decenter), and tilt <0.15 degrees (for a 5 degree tilt).

Reconstructing ocular surfaces by Purkinje images: an exact ray approach.

A method originally developed for corneal topography (using discrete sources and Zernike polynomials) was extended to estimate the geometry of ocular surfaces internal to the eye. The approach was tested in simulation as a candidate method for phakometry. Purkinje images from the anterior surface of an intra-ocular lens (IOL) (aligned and decentered) were simulated using the Navarro eye. The 'full' Navarro eye and a simplified eye were assumed for recovery purposes. Root mean square (RMS) errors and (anterior) IOL radii of curvatures (best-fit spheres) were estimated. The robustness of the method to axial shifts in lens position (both eye models) along with assumed refractive index (simplified eye only) was tested. When axial shifts were ignored, RMS errors for the full eye were sub-micron (<0.8 microm), and radii of curvature errors were approximately 1 microm. Axial shifting increased these errors linearly. The n = 1.32 error curve (simplified eye) matched the full eye error curves closely (for both RMS error and IOL lens radius), although the RMS error curve exhibited some asymmetry for a decentered IOL. The nominal refractive index (n = 1.3305) was sub-optimal in all cases. The resulting method is a potentially useful way to estimate the geometry of the internal ocular surfaces.