Novel Quantitative Contrast Sensitivity Function Enhances the Prediction of Treatment Outcome and Recurrence in Amblyopia.

Purpose: Although effective amblyopia treatments are available, treatment outcome is unpredictable, and the condition recurs in up to 25% of the patients. We aimed to evaluate whether a large-scale quantitative contrast sensitivity function (CSF) data source, coupled with machine learning (ML) algorithms, can predict amblyopia treatment response and recurrence in individuals. Methods: Visual function measures from traditional chart vision acuity (VA) and novel CSF assessments were used as the main predictive variables in the models. Information from 58 potential predictors was extracted to predict treatment response and recurrence. Six ML methods were applied to construct models. The SHapley Additive exPlanations was used to explain the predictions. Results: A total of 2559 consecutive records of 643 patients with amblyopia were eligible for modeling. Combining variables from VA and CSF assessments gave the highest accuracy for treatment response prediction, with the area under the receiver operating characteristic curve (AUC) of 0.863 and 0.815 for outcome predictions after 3 and 6 months, respectively. Variables from the VA assessment alone predicted the treatment response, with AUC values of 0.723 and 0.675 after 3 and 6 months, respectively. Variables from the CSF assessment gave rise to an AUC of 0.909 for recurrence prediction compared to 0.539 for VA assessment alone, and adding VA variables did not improve predictive performance. The interocular differences in CSF features are significant contributors to recurrence risk. Conclusions: Our models showed CSF data could enhance treatment response prediction and accurately predict amblyopia recurrence, which has the potential to guide amblyopia management by enabling patient-tailored decision making.

Association between time spent on smartphones and digital eye strain: A 1-year prospective observational study among Hong Kong children and adolescents.

Prolonged electronic screen use can cause digital eye strain. It can be difficult to rectify due to increasing smartphone reliance, potentially leading to serious public health problems. To investigate the association between time spent on smartphones and digital eye strain (DES) among Hong Kong Chinese school-aged children. Of a total of 1,508 students (748 males, 49.6%) from 8 to 14 years old (mean age = 10.91 years, SD = 2.01) who provided valid data on DES, the 1,298 (86%) who completed the DES questionnaire at 1-year follow-up were included in the analysis. DES was measured using a 10-item scale, and the sum of the 10 dichotomised scores was used as the DES total score. The most commonly reported symptoms were eye fatigue (n = 804, 53.3%), blurred vision (changing from reading to distance viewing) (n = 586, 38.9%), and irritated or burning eyes (n = 516, 34.2%). The DES total scores at baseline and 1-year follow-up were 2.91 (SD = 2.90) and 3.20 (SD = 3.19), respectively. Linear regression controlling for demographic and socio-economic confounders showed that participants with baseline smartphone usage of 241 + min/d had a significantly higher baseline total DES score than those with baseline smartphone usage of 0-60 min/d (2.44 vs 3.21, P < 0.001), and participants with baseline smartphone usage of 181-240 min/d had a significantly higher 1-year follow-up total DES score than those with baseline smartphone usage of 0-60 min/d (2.80 vs 3.50, P = 0.003).

Bilberry-containing supplements on severe dry eye disease in young and middle-aged adults: A 3-month pilot analysis.

Purpose: To explore the effect of bilberry and fish oil combination supplement on a small clinical sample patient-base with severe dry eyes. Methods: Twenty-four subjects were recruited with twelve randomly assigned to the intervention and control groups, respectively. Inclusion criteria included severe dry eye symptoms determined by scores >33 from the Ocular Surface Disease Index (OSDI) questionnaire. The intervention group was instructed to take an oral supplement with key ingredients of 600 mg bilberry extract and 240 mg docosahexaenoic acid-refined fish oil once daily for 3 months. The control group did not take any supplements. Mean changes in OSDI score, non-invasive tear break-up time (NITBUT), phenol red thread test (PRT), and percentage of meibomian gland openings were used as outcome measures. Testing was done at baseline, 1-month, and 3-month follow-up. Comparison between the treatment and control groups, and the younger adult and middle-age groups were performed. Results: The mean baseline values for the treatment and control groups were not clinically different. The OSDI score, NITBUT, PRT, and percentage of meibomian gland openings improved after taking the supplements for 3 months. The OSDI score, NITBUT, and PRT showed clinical improvements between the intervention and control groups. These improvements were consistent between the two age groups. Conclusion: This study suggested preliminary improvements in signs and symptoms of severe dry eyes that were independent of age after taking dietary supplementation of bilberry extract and fish oil for 3 months. Further studies using more device-based measures and a placebo supplement are warranted.

Assessing the contrast sensitivity function in myopic parafovea: A quick contrast sensitivity functions study.

Purpose: Compare peripheral contrast sensitivity functions (CSF) between myopes and emmetropes to reveal potential myogenic risks during emmetropization. Materials and methods: This observational, cross-sectional, non-consecutive case study included data from 19 myopes (23.42 ± 4.03 years old) and 12 emmetropes (22.93 ± 2.91 years old) who underwent central and peripheral quick CSF (qCSF) measurements. Summary CSF metrics including the cut-off spatial frequency (cut-off SF), area under log CSF (AULCSF), low-, intermediate-, and high-spatial-frequency AULCSFs (l-, i-, and h-SF AULCSFs), and log CS at 19 SFs in the fovea and 15 peripheral locations (superior, inferior, temporal, and nasal quadrants at 6, 12, 18, and 24° eccentricities, excluding the physiological scotoma at 18°) were analyzed with 3-way and 4-way between-subjects analysis of variance (ANOVA) (α = 0.05). Results: Three-way ANOVA showed that myopes had significantly increased AULCSF at 6° (mean difference, 0.08; 95% CI, 0.02-0.13; P = 0.007) and 12° (mean difference, 0.09; 95% CI, 0.03-0.14; P = 0.003). Log CS at all 19 SFs were higher in the myopia group compared to the normal group (mean differencesuperior, 0.02; 95% CI, 0.01-0.20; P = 0.02 and mean differenceinferior, 0.11; 95% CI, 0.02-0.21; P = 0.01) at 12°. The h-SF AULCSF at 6° (mean differenceinferior, 1.27; 95% CI, 0.32-2.22; P = 0.009) and i-SF AULCSF at 12° (mean differencesuperior, 5.31; 95% CI, 4.35-6.27; P < 0.001; mean differenceinferior, 1.14; 95% CI, 0.19-2.10; P = 0.02) were higher in myopia vs. normal group. Conclusion: We found myopia increased contrast sensitivity in superior and inferior visual field locations at 6° parafoveal and 12° perifoveal regions of the retina. The observation of increased contrast sensitivities within the macula visual field in myopia might provide important insights for myopia control during emmetropization.

The Integration of Eye Tracking Responses for the Measurement of Contrast Sensitivity: A Proof of Concept Study.

Contrast sensitivity (CS) is important when assessing functional vision. However, current techniques for assessing CS are not suitable for young children or non-verbal individuals because they require reliable, subjective perceptual reports. This study explored the feasibility of applying eye tracking technology to quantify CS as a first step toward developing a testing paradigm that will not rely on observers' behavioral or language abilities. Using a within-subject design, 27 healthy young adults completed CS measures for three spatial frequencies with best-corrected vision and lens-induced optical blur. Monocular CS was estimated using a five-alternative, forced-choice grating detection task. Thresholds were measured using eye movement responses and conventional key-press responses. CS measured using eye movements compared well with results obtained using key-press responses [Pearson's r best-corrected = 0.966, P < 0.001]. Good test-retest variability was evident for the eye-movement-based measures (Pearson's r = 0.916, P < 0.001) with a coefficient of repeatability of 0.377 log CS across different days. This study provides a proof of concept that eye tracking can be used to automatically record eye gaze positions and accurately quantify human spatial vision. Future work will update this paradigm by incorporating the preferential looking technique into the eye tracking methods, optimizing the CS sampling algorithm and adapting the methodology to broaden its use on infants and non-verbal individuals.

Sensitivity and Stability of Functional Vision Tests in Detecting Subtle Changes Under Multiple Simulated Conditions.

Purpose: To explore whether subtle changes in visual quality can be detected using different measures of visual function against the quick contrast sensitivity function test (quick CSF). Methods: Sixty participants, aged 17 to 34 years, were enrolled. Participants' vision was degraded by 0.25 D undercorrection (0.25 D), 60% neutral density filter brightness reduction (60% ND), and 0.8 Bangerter foil optical diffusion (0.8BAN). Visual function tests including visual acuity and contrast sensitivity (CSV-1000E and quick CSF) were measured with participant's best-corrected vision and under simulated visual degradation conditions. Test sensitivities in detecting differences were compared. Results: Statistically significant visual acuity degradation was observed in the 0.8BAN condition only (Pcorrected < 0.001). With CSV-1000E and outliers removed, significant CS degradation was observed in all spatial frequencies, area under log CSF (AULCSF) in the 0.8BAN condition (Pcorrected < 0.001 for all), medium and high spatial frequencies and AULCSF in the 60%ND condition (Pcorrected,6cpd = 0.002, Pcorrected,12cpd = 0.005, Pcorrected,18cpd = 0.001, Pcorrected,AULCSF < 0.001) and the 0.25 D condition (Pcorrected,6cpd = 0.011, Pcorrected,12cpd = 0.013, Pcorrected,18cpd = 0.015, Pcorrected,AULCSF < 0.001). With the quick CSF, significant CS degradation was observed in all simulated visual conditions in all spatial frequencies, cutoff frequency and AULCSF (Pcorrected < 0.001 for all). Test-retest reliability of the quick CSF method was high; coefficient of repeatability ranged from 0.14 to 0.18 logCS. Conclusions: Compared with visual acuity and chart-based CS tests, the quick CSF method provided more reliable and sensitive measures to detect small visual changes. Translational Relevance: The quick CSF method can provide sensitive and reliable measures to monitor disease progression and assess treatment outcomes.

Association between Time Spent on Smart Devices and Change in Refractive Error: A 1-Year Prospective Observational Study among Hong Kong Children and Adolescents.

This study examined the association between smart device usage and the 1-year change in refractive error among a representative sample of Hong Kong children and adolescents aged 8-14 years. A total of 1597 participants (49.9% male, mean age 10.9, SD 2.0) who completed both baseline (2017-2018) and 1-year follow-up (2018-2019) eye examinations were included in the present study. The non-cycloplegic auto-refractive error was measured and the average spherical equivalent refraction (SER) was analyzed. The participants also self-reported their smart device usage at baseline. Multivariate regression adjusted for age, sex, baseline SER, parents' short-sightedness, BMI, time spent on moderate-to-vigorous physical activity (MVPA), and caregiver-reported socio-economic status showed that, compared with the reference group (<2 h per day on both smartphone and tablet usages), those who spent ≥2 h per day using a smartphone and <2 h per day using a tablet had a significantly negative shift in refractive error (1-year change in SER -0.25 vs. -0.09 D, p = 0.01) for the right eye, while the level of significance was marginal (1-year change -0.28 vs. -0.15 D, p = 0.055) for the left eye. To conclude, our data suggested spending at most 2 h per day on both smartphones and tablets.

Dichoptic training improves contrast sensitivity in adults with amblyopia.

Dichoptic training is designed to promote binocular vision in patients with amblyopia. Initial studies have found that the training effects transfer to both binocular (stereopsis) and monocular (recognition acuity) visual functions. The aim of this study was to assess whether dichoptic training effects also transfer to contrast sensitivity (CS) in adults with amblyopia. We analyzed CS data from 30 adults who had taken part in one of two previous dichoptic training studies and assessed whether the changes in CS exceeded the 95% confidence intervals for change based on test-retest data from a separate group of observers with amblyopia. CS was measured using Gabor patches (0.5, 3 and 10cpd) before and after 10days of dichoptic training. Training was delivered using a dichoptic video game viewed through video goggles (n=15) or on an iPod touch equipped with a lenticular overlay screen (n=15). In the iPod touch study, training was combined with anodal transcranial direct current stimulation of the visual cortex. We found that dichoptic training significantly improved CS across all spatial frequencies tested for both groups. These results suggest that dichoptic training modifies the sensitivity of the neural systems that underpin monocular CS.

Quantitative measurement of interocular suppression in anisometropic amblyopia: a case-control study.

OBJECTIVE: The aims of this study were to assess (1) the relationship between interocular suppression and visual function in patients with anisometropic amblyopia, (2) whether suppression can be simulated in matched controls using monocular defocus or neutral density filters, (3) the effects of spectacle or rigid gas-permeable contact lens correction on suppression in patients with anisometropic amblyopia, and (4) the relationship between interocular suppression and outcomes of occlusion therapy. DESIGN: Case-control study (aims 1-3) and cohort study (aim 4). PARTICIPANTS: Forty-five participants with anisometropic amblyopia and 45 matched controls (mean age, 8.8 years for both groups). METHODS: Interocular suppression was assessed using Bagolini striated lenses, neutral density filters, and an objective psychophysical technique that measures the amount of contrast imbalance between the 2 eyes that is required to overcome suppression (dichoptic motion coherence thresholds). Visual acuity was assessed using a logarithm minimum angle of resolution tumbling E chart and stereopsis using the Randot preschool test. MAIN OUTCOME MEASURES: Interocular suppression assessed using dichoptic motion coherence thresholds. RESULTS: Patients exhibited significantly stronger suppression than controls, and stronger suppression was correlated significantly with poorer visual acuity in amblyopic eyes. Reducing monocular acuity in controls to match that of cases using neutral density filters (luminance reduction) resulted in levels of interocular suppression comparable with that in patients. This was not the case for monocular defocus (optical blur). Rigid gas-permeable contact lens correction resulted in less suppression than spectacle correction, and stronger suppression was associated with poorer outcomes after occlusion therapy. CONCLUSIONS: Interocular suppression plays a key role in the visual deficits associated with anisometropic amblyopia and can be simulated in controls by inducing a luminance difference between the eyes. Accurate quantification of suppression using the dichoptic motion coherence threshold technique may provide useful information for the management and treatment of anisometropic amblyopia. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Dichoptic training enables the adult amblyopic brain to learn.

Adults with amblyopia, a common visual cortex disorder caused primarily by binocular disruption during an early critical period, do not respond to conventional therapy involving occlusion of one eye. But it is now clear that the adult human visual cortex has a significant degree of plasticity, suggesting that something must be actively preventing the adult brain from learning to see through the amblyopic eye. One possibility is an inhibitory signal from the contralateral eye that suppresses cortical inputs from the amblyopic eye. Such a gating mechanism could explain the apparent lack of plasticity within the adult amblyopic visual cortex. Here we provide direct evidence that alleviating suppression of the amblyopic eye through dichoptic stimulus presentation induces greater levels of plasticity than forced use of the amblyopic eye alone. This indicates that suppression is a key gating mechanism that prevents the amblyopic brain from learning to see.

How best to assess suppression in patients with high anisometropia.

PURPOSE: We have recently described a rapid technique for measuring suppression using a dichoptic signal/noise task. Here, we report a modification of this technique that allows for accurate measurements to be made in amblyopic patients with high levels of anisometropia. This was necessary because aniseikonic image size differences between the two eyes can provide a cue for signal/noise segregation and, therefore, influence suppression measurement in these patients. METHODS: Suppression was measured using our original technique and with a modified technique whereby the size of the signal and noise elements was randomized across the stimulus to eliminate size differences as a cue for task performance. Eleven patients with anisometropic amblyopia, five with more than 5 diopters (D) spherical equivalent difference (SED), six with less than 5 D SED between the eyes, and 10 control observers completed suppression measurements using both techniques. RESULTS: Suppression measurements in controls and patients with less than 5 D SED were constant across the two techniques; however, patients with more than 5 D SED showed significantly stronger suppression on the modified technique with randomized element size. Measurements made with the modified technique correlated with the loss of visual acuity in the amblyopic eye and were in good agreement with previous reports using detailed psychophysical measurements. CONCLUSIONS: The signal/noise technique for measuring suppression can be applied to patients with high levels of anisometropia and aniseikonia if element size is randomized. In addition, deeper suppression is associated with a greater loss of visual acuity in patients with anisometropic amblyopia.

Does partial occlusion promote normal binocular function?

PURPOSE: There is growing evidence that abnormal binocular interactions play a key role in the amblyopia syndrome and represent a viable target for treatment interventions. In this context the use of partial occlusion using optical devices such as Bangerter filters as an alternative to complete occlusion is of particular interest. The aims of this study were to understand why Bangerter filters do not result in improved binocular outcomes compared to complete occlusion, and to compare the effects of Bangerter filters, optical blur and neutral density (ND) filters on normal binocular function. METHODS: The effects of four strengths of Bangerter filters (0.8, 0.6, 0.4, 0.2) on letter and vernier acuity, contrast sensitivity, stereoacuity, and interocular suppression were measured in 21 observers with normal vision. In a subset of 14 observers, the partial occlusion effects of Bangerter filters, ND filters and plus lenses on stereopsis and interocular suppression were compared. RESULTS: Bangerter filters did not have graded effect on vision and induced significant disruption to binocular function. This disruption was greater than that of monocular defocus but weaker than that of ND filters. The effect of the Bangerter filters on stereopsis was more pronounced than their effect on monocular acuity, and the induced monocular acuity deficits did not predict the induced deficits in stereopsis. CONCLUSIONS: Bangerter filters appear to be particularly disruptive to binocular function. Other interventions, such as optical defocus and those employing computer generated dichoptic stimulus presentation, may be more appropriate than partial occlusion for targeting binocular function during amblyopia treatment.

The role of suppression in amblyopia.

PURPOSE: This study had three main goals: to assess the degree of suppression in patients with strabismic, anisometropic, and mixed amblyopia; to establish the relationship between suppression and the degree of amblyopia; and to compare the degree of suppression across the clinical subgroups within the sample. METHODS: Using both standard measures of suppression (Bagolini lenses and neutral density [ND] filters, Worth 4-Dot test) and a new approach involving the measurement of dichoptic motion thresholds under conditions of variable interocular contrast, the degree of suppression in 43 amblyopic patients with strabismus, anisometropia, or a combination of both was quantified. RESULTS: There was good agreement between the quantitative measures of suppression made with the new dichoptic motion threshold technique and measurements made with standard clinical techniques (Bagolini lenses and ND filters, Worth 4-Dot test). The degree of suppression was found to correlate directly with the degree of amblyopia within our clinical sample, whereby stronger suppression was associated with a greater difference in interocular acuity and poorer stereoacuity. Suppression was not related to the type or angle of strabismus when this was present or the previous treatment history. CONCLUSIONS: These results suggest that suppression may have a primary role in the amblyopia syndrome and therefore have implications for the treatment of amblyopia.

Relationships among diabetic retinopathy, antioxidants, and glycemic control.

PURPOSE: Type 2 Diabetes Mellitus (DM) is increasing worldwide and affects ∼11% of the Hong Kong population. Diabetic retinopathy (DR) is a common cause of vision loss in type 2 DM. Risk of DR is increased by poor glycemic control, elevated lipids, and blood pressure, but it is not possible to predict the development or progression of DR at an individual level. Increased oxidative stress is thought to play a role. The use of a wider biomarker profile incorporating biomarkers of antioxidant status and oxidative stress may aid identification of individuals at higher risk or at very early stages of developing DR. METHODS: Four hundred twenty type 2 DM subjects without diabetic complications were investigated. Eyes were examined for DR and anterior and posterior ocular segment pathology. DR was graded according to Early Treatment Diabetic Retinopathy Study criteria. Demographic data were collected. Traditional risk factors plus biomarkers of antioxidant status and oxidative stress in fasting blood and urine were determined. RESULTS: Overall DR prevalence was 89%. No significant differences in any demographic measures or biomarkers were found among those subjects with different DR grades, or in those without DR. Significant correlations (p < 0.0001) between HbA1c and DNA damage, (ρ = 0.32) and fasting plasma glucose and DNA damage (ρ = 0.52) were seen. DNA damage was also significantly and inversely correlated (p < 0.0001) with both plasma ascorbic acid (ρ = -0.41) and plasma total antioxidant level (ρ = -0.21). CONCLUSIONS: DR prevalence was very high in this group, but no biomarker differences were seen in those with DR compared to those free of DR, or in those with different degrees of severity of DR. This group of 420 subjects is being followed up to investigate whether the extended biomarker profile at baseline is related to progression of and/or incident DR.

Quantifying sensory eye dominance in the normal visual system: a new technique and insights into variation across traditional tests.

PURPOSE: Although eye dominance assessment is used to assist clinical decision-making, current understanding is limited by inconsistencies across the range of available tests. A new psychophysical test of sensory eye dominance has been developed that objectively measures the relative contribution of each eye to a fused suprathreshold binocular percept. METHODS: Six standard tests and the newly developed test were used to measure motor and sensory dominance in a group of 44 binocularly normal individuals (mean age, 29.5 ± 9.10 years). The new test required observers to perform a motion coherence task under dichoptic viewing conditions, wherein a population of moving, luminance-defined signal (coherently moving) and noise (randomly moving) dots were presented separately to each eye. The observers judged the motion direction of the signal dots. Motion coherence thresholds were measured by varying the ratio of signal-to-noise dots, in a staircase procedure. RESULTS: The new dichoptic motion coherence threshold test revealed a clear bimodal distribution of sensory eye dominance strength, wherein the majority of the participants (61%) showed weak dominance, but a significant minority (39%) showed strong dominance. Subsequent analysis revealed that the strong-dominance group showed greater consistency across the range of traditional eye dominance tests used. CONCLUSIONS: This new quantitative dichoptic motion coherence threshold technique suggests that there are two separate sensory eye dominance strength distributions among observers with normal binocular vision: weak and strong eye dominance. This finding may provide a basis for clinical decision-making by indicating whether eye dominance is likely to be an important consideration in a particular patient.