Biometric and refractive changes following the monocular application of peripheral myopic defocus using a novel augmented-reality optical system in adults.

The prevalence of myopia is growing at an alarming rate and is associated with axial elongation of the eye. The cause of this undesirable physiological change involves multiple factors. When the magnitude of myopia approaches high levels, this accompanying mechanical effect increases the risk of developing other clinical conditions associated with permanent vision loss. Prior work has investigated how we may halt or reverse this process of axial elongation associated with myopic progression when we expose the eye to a peripheral myopic defocus stimulus. Specifically, the known, short-term response to myopic defocus stimulation is promising and demonstrates the possibility of establishing more permanent effects by regulating the axial length of the eye with specific defocus stimulation. However, how to directly convert these known, short-term effects into more long-term, permanent changes to effectively prevent these unfavourable physiological and refractive changes over time is yet to be understood. Here, we show for the first time that we can produce sustained, long-term reductions in axial length and refractive endpoints with cumulative short-term exposure to specific myopic defocus stimuli using a novel optical design that incorporates an augmented reality optical system. We believe that this technology will have the potential to improve the quality of vision in mankind.

Effect of short-term peripheral myopic defocus on ocular biometrics using Fresnel "press-on" lenses in humans.

This study assessed axial length and choroidal thickness changes following short-term peripheral myopic defocus in normal adult subjects. Twenty subjects underwent defocus sessions by viewing a full-field projected movie 4 m away for 4 h in the morning, while wearing spectacle lenses, corrected for distance vision in both eyes. The right eye, serving as the test eye, was peripherally defocused using a Fresnel lens overlay of + 3.50 D with a central clear aperture of 11.5 mm (correlating to a clear central visual field of approximately 23°), while the left eye served as the control (with no Fresnel lens overlay). A subset of 10 subjects from the same cohort also underwent additional defocus sessions with + 5.00 D of peripheral defocus. Axial length was measured and radial sub-foveal choroidal scans were obtained before and after the defocus sessions. The increase in axial length of the test eyes were significantly less than the control eyes under both peripheral defocus conditions (p < 0.05). The difference in mean change for choroidal thickness between test and control eyes was not significant for either dioptric condition. Our results demonstrated that short-term peripheral myopic defocus significantly inhibited axial elongation in adult humans, without significant changes in choroidal thickness.

Visual Performance as a Function of Clear Central Aperture Diameter with a Defocused Myopic Periphery.

SIGNIFICANCE: Visual performance is affected least by a 15° radial aperture surrounded by peripheral myopic defocus. This finding has important applications for spectacle and contact lens designs and myopia control optimization. PURPOSE: The purpose of this study was to assess the effect of clear central apertures of different diameters with a defocused retinal periphery, using a range of visual performance tasks. METHODS: Thirty visually normal subjects (mean age, 24.4 ± 3.3 years; 20 females; mean spherical equivalent of -1.28 D) were enrolled. Subjects wore five different spectacles during testing, all corrected for distance refraction, in random order: three single-vision spectacles with clear central apertures of 10, 12.5, and 15° radii with the periphery defocused using Fresnel "press-on" lenses (+3.5 D sphere), progressive addition lens (PAL) spectacles with a +3.5 D addition, and single-vision lens (SVL) spectacles with no peripheral defocus. Static and kinetic visual field sensitivities, reading rate and comprehension, head movements, global saccadic tracking, and saccadic visual search were evaluated. RESULTS: Reading rate and comprehension did not differ across the five test conditions; however, increased head movement was found with the smallest aperture compared with the PAL condition with adjusted P < .05. Static visual field sensitivity was reduced for all three apertures in eccentric regions when compared with the SVL and PAL conditions with adjusted P < .05, whereas kinetic sensitivity did not differ for any lens condition. The 15° aperture was superior to the 10 and 12.5° apertures based on its similarity to the SVL and PAL spectacle conditions in head movement during reading, the Michigan Tracking Test, and the vertical results of the Developmental Eye Movement Test. CONCLUSIONS: Visual performance is least affected adversely by a 15° aperture surrounded by a peripheral myopic defocus. This finding has important applications for spectacle and contact lens designs to optimize myopia treatment with minimal impact on visual performance.

Developmental Effects on Pattern Visual Evoked Potentials Characterized by Principal Component Analysis.

Purpose: Peak amplitude and peak latency in the pattern reversal visual evoked potential (prVEP) vary with maturation. We considered that principal component analysis (PCA) may be used to describe age-related variation over the entire prVEP time course and provide a means of modeling and removing variation due to developmental age. Methods: PrVEP was recorded from 155 healthy subjects ages 11 to 19 years at two time points. We created a model of the prVEP by identifying principal components (PCs) that explained >95% of the variance in a "training" dataset of 40 subjects. We examined the ability of the PCs to explain variance in an age- and sex-matched "validation" dataset (n = 40) and calculated the intrasubject reliability of the PC coefficients between the two time points. We explored the effect of subject age and sex upon the PC coefficients. Results: Seven PCs accounted for 96.0% of the variability of the training dataset and 90.5% of the variability in the validation dataset with good within-subject reliability across time points (R > 0.7 for all PCs). The PCA model revealed narrowing and amplitude reduction of the P100 peak with maturation, and a broader and smaller P100 peak in male subjects compared to female subjects. Conclusions: PCA is a generalizable, reliable, and unbiased method of analyzing prVEP. The PCA model revealed changes across maturation and biological sex not fully described by standard peak analysis. Translational Relevance: We describe a novel application of PCA to characterize developmental changes of prVEP in youths that can be used to compare healthy and pathologic pediatric cohorts.

Utility of Pupillary Light Reflex Metrics as a Physiologic Biomarker for Adolescent Sport-Related Concussion.

Importance: Concussion diagnosis remains clinical, without objective diagnostic tests available for adolescents. Known deficits in visual accommodation and autonomic function after concussion make the pupillary light reflex (PLR) a promising target as an objective physiological biomarker for concussion. Objective: To determine the potential utility of PLR metrics as physiological biomarkers for concussion. Design, Setting, and Participants: Prospective cohort of adolescent athletes between ages 12 and 18 years recruited between August 1, 2017, and December 31, 2018. The study took place at a specialty concussion program and private suburban high school and included healthy control individuals (n = 134) and athletes with a diagnosis of sport-related concussion (SRC) (n = 98). Analysis was completed June 30, 2020. Exposures: Sports-related concussion and pupillometry assessments. Main Outcomes and Measures: Pupillary light reflex metrics (maximum and minimum pupillary diameter, peak and average constriction/dilation velocity, percentage constriction, and time to 75% pupillary redilation [T75]). Results: Pupillary light reflex metrics of 134 healthy control individuals and 98 athletes with concussion were obtained a median of 12.0 days following injury (interquartile range [IQR], 5.0-18.0 days). Eight of 9 metrics were significantly greater among athletes with concussion after Bonferroni correction (maximum pupil diameter: 4.83 mm vs 4.01 mm; difference, 0.82; 99.44% CI, 0.53-1.11; minimum pupil diameter: 2.96 mm vs 2.63 mm; difference, 0.33; 99.4% CI, 0.18-0.48; percentage constriction: 38.23% vs 33.66%; difference, 4.57; 99.4% CI, 2.60-6.55; average constriction velocity: 3.08 mm/s vs 2.50 mm/s; difference, 0.58; 99.4% CI, 0.36-0.81; peak constriction velocity: 4.88 mm/s vs 3.91 mm/s; difference, 0.97; 99.4% CI, 0.63-1.31; average dilation velocity, 1.32 mm/s vs 1.22 mm/s; difference, 0.10; 99.4% CI, 0.00-0.20; peak dilation velocity: 1.83 mm/s vs 1.64 mm/s; difference, 0.19; 99.4% CI, 0.07-0.32; and T75: 1.81 seconds vs 1.51 seconds; difference, 0.30; 0.10-0.51). In exploratory analyses, sex-based differences were observed, with girls with concussion exhibiting longer T75 (1.96 seconds vs 1.63 seconds; difference, 0.33; 99.4% CI, 0.02-0.65). Among healthy control individuals, diminished PLR metrics (eg, smaller maximum pupil size 3.81 mm vs 4.22 mm; difference, -0.41; 99.4% CI, -0.77 to 0.05) were observed after exercise. Conclusions and Relevance: These findings suggest that enhancement of PLR metrics characterize acute adolescent concussion, while exercise produced smaller pupil sizes and overall slowing of PLR metrics, presumably associated with fatigue. Quantifiable measures of the PLR may serve in the future as objective physiologic biomarkers for concussion in the adolescent athlete.

Influence of refractive error on pupillary dynamics in the normal and mild traumatic brain injury (mTBI) populations / Influencia del error refractivo sobre la dinámica pupilar en las poblaciones normales y las afectadas de lesiones cerebrales traumáticas leves (mTBI)

Purpose: There have been several studies investigating static, baseline pupil diameter in visually-normal individuals across refractive error. However, none have assessed the dynamic pupillary light reflex (PLR). In the present study, both static and dynamic pupillary parameters of the PLR were assessed in both the visually-normal (VN) and the mild traumatic brain injury (mTBI) populations and compared as a function of refractive error. Methods: The VN population comprised 40 adults (22-56 years of age), while the mTBI population comprised 32 adults (21-60 years of age) over a range of refractive errors (-9.00 D to +1.25 D). Seven pupillary parameters (baseline static diameter, latency, amplitude, and peak and average constriction and dilation velocities) were assessed and compared under four white light stimulus conditions (dim pulse, dim step, bright pulse, and bright step). The Neuroptics, infrared, DP-2000 binocular pupillometer (30 Hz sampling rate; 0.05 mm resolution) was used in the monocular (right eye) stimulation mode. Results: For the majority of pupillary parameters and stimulus conditions, a Gaussian distribution best fit the data, with the apex centered in the low myopic range (-2.3 to -4.9D). Responsivity was reduced to either side of the apex. Conclusions: Over a range of dynamic and static pupillary parameters, the PLR was influenced by refractive error in both populations. In cases of high refractive error, the PLR parameters may need to be compensated for this factor for proper categorization and diagnosis

Objetivo: Existen diversos estudios que han investigado el diámetro pupilar estático y basal en individuos con visión normal en todo el espectro de errores refractivos. Sin embargo, ninguno de ellos ha evaluado el reflejo dinámico pupilar a la luz (RPL). En el presente estudio, se evaluaron tanto los parámetros pupilares estáticos como los dinámicos en poblaciones con visión normal (VN) y en las afectadas de lesiones cerebrales traumáticas leves (mTBI), comparándolos en función del error refractivo. Métodos: La población VN incluyó a 40 adultos (de 22 a 56 años de edad), mientras que el grupo de mTBI incluyó a 32 adultos (de 21 a 60 años de edad) para un rango de errores refractivos (de -9D a + 1,25D). Se valoraron siete parámetros pupilares (diámetro estático basal, latencia, amplitud, constricción máxima y media, y velocidades de dilatación), comparándose bajo cuatro situaciones de estímulo con luz blanca (pulso tenue, punto tenue, pulso brillante, y punto brillante). Se utilizó el pupilómetro binocular con infrarrojos DP-200 de Neuroptics (30 Hz de muestreo; 0,05 mm de resolución) en el modo de estimulación monocular (ojo derecho). Resultados: Para la mayoría de los parámetros pupilares y situaciones de estímulo, los datos se ajustaron a una distribución gausiana, centrándose el ápex en el rango miópico bajo (-2,3 to -4,9D). La respuesta se redujo a ambos extremos del ápex. Conclusiones: Para un rango de parámetros pupilares dinámicos y estáticos, el RPL se vio influenciado por el error refractivo en ambas poblaciones. En casos de error refractivo elevado, los parámetros de RPL pueden necesitar compensarse por este factor, para su debida categorización y diagnóstico

Influence of refractive error on pupillary dynamics in the normal and mild traumatic brain injury (mTBI) populations.

PURPOSE: There have been several studies investigating static, baseline pupil diameter in visually-normal individuals across refractive error. However, none have assessed the dynamic pupillary light reflex (PLR). In the present study, both static and dynamic pupillary parameters of the PLR were assessed in both the visually-normal (VN) and the mild traumatic brain injury (mTBI) populations and compared as a function of refractive error. METHODS: The VN population comprised 40 adults (22-56 years of age), while the mTBI population comprised 32 adults (21-60 years of age) over a range of refractive errors (-9.00D to +1.25D). Seven pupillary parameters (baseline static diameter, latency, amplitude, and peak and average constriction and dilation velocities) were assessed and compared under four white-light stimulus conditions (dim pulse, dim step, bright pulse, and bright step). The Neuroptics, infrared, DP-2000 binocular pupillometer (30Hz sampling rate; 0.05mm resolution) was used in the monocular (right eye) stimulation mode. RESULTS: For the majority of pupillary parameters and stimulus conditions, a Gaussian distribution best fit the data, with the apex centered in the low myopic range (-2.3 to -4.9D). Responsivity was reduced to either side of the apex. CONCLUSIONS: Over a range of dynamic and static pupillary parameters, the PLR was influenced by refractive error in both populations. In cases of high refractive error, the PLR parameters may need to be compensated for this factor for proper categorization and diagnosis.

Intensity response function of the photopic negative response (PhNR): effect of age and test-retest reliability.

PURPOSE: To assess the effect of age and test-retest reliability of the intensity response function of the full-field photopic negative response (PhNR) in normal healthy human subjects. METHODS: Full-field electroretinograms (ERGs) were recorded from one eye of 45 subjects, and 39 of these subjects were tested on two separate days with a Diagnosys Espion System (Lowell, MA, USA). The visual stimuli consisted of brief (<5 ms) red flashes ranging from 0.00625 to 6.4 phot cd.s/m2, delivered on a constant 7 cd/m2 blue background. PhNR amplitudes were measured at its trough from baseline (BT) and from the preceding b-wave peak (PT), and b-wave amplitude was measured at its peak from the preceding a-wave trough or baseline if the a-wave was not present. The intensity response data of all three ERG measures were fitted with a generalized Naka-Rushton function to derive the saturated amplitude (V max), semisaturation constant (K) and slope (n) parameters. Effect of age on the fit parameters was assessed with linear regression, and test-retest reliability was assessed with the Wilcoxon signed-rank test and Bland-Altman analysis. Holm's correction was applied to account for multiple comparisons. RESULTS: V max of BT was significantly smaller than that of PT and b-wave, and the V max of PT and b-wave was not significantly different from each other. The slope parameter n was smallest for BT and the largest for b-wave and the difference between the slopes of all three measures were statistically significant. Small differences observed in the mean values of K for the different measures did not reach statistical significance. The Wilcoxon signed-rank test indicated no significant differences between the two test visits for any of the Naka-Rushton parameters for the three ERG measures, and the Bland-Altman plots indicated that the mean difference between test and retest measurements of the different fit parameters was close to zero and within 6% of the average of the test and retest values of the respective parameters for all three ERG measurements, indicating minimal bias. While the coefficient of reliability (COR, defined as 1.96 times the standard deviation of the test and retest difference) of each fit parameter was more or less comparable across the three ERG measurements, the %COR (COR normalized to the mean test and retest measures) was generally larger for BT compared to both PT and b-wave for each fit parameter. The Naka-Rushton fit parameters did not show statistically significant changes with age for any of the ERG measures when corrections were applied for multiple comparisons. However, the V max of BT demonstrated a weak correlation with age prior to correction for multiple comparisons, and the effect of age on this parameter showed greater significance when the measure was expressed as a ratio of the V max of b-wave from the same subject. CONCLUSION: V max of the BT amplitude measure of PhNR at the best was weakly correlated with age. None of the other parameters of the Naka-Rushton fit to the intensity response data of either the PhNR or the b-wave showed any systematic changes with age. The test-retest reliability of the fit parameters for PhNR BT amplitude measurements appears to be lower than those of the PhNR PT and b-wave amplitude measurements.

Understanding the effects of mild traumatic brain injury on the pupillary light reflex.

The pupillary light reflex represents an optimal visual system to investigate and exploit in the mild traumatic brain injury (mTBI) population. Static and dynamic aspects of the pupillary light reflex were investigated objectively and quantitatively in the mTBI population. Pupillary responsivity was found to be significantly delayed, slowed and reduced, but symmetrical in nature, and with a smaller baseline diameter, as compared with normals. Several pupillary parameters also discriminated between those with versus without photosensitivity. Thus, dynamic pupillometry provides several objective biomarkers for the presence of mTBI and photosensitivity, gives insight into the global sites of neurological dysfunction and possible related mechanisms, and should result in improved patient care.