Intereye Differences in the Clinical Assessment of Intraocular Pressure and Ocular Biomechanics.

SIGNIFICANCE: Clinicians and researchers will have evidence whether intereye differences confound clinical measurements of intraocular pressure or of ocular biomechanical parameters. PURPOSE: The purpose of this study was to determine whether intraocular pressure and biomechanical parameters, as measured by the Ocular Response Analyzer (ORA) and by Cornea Visualization with Scheimpflug Technology (CorVis ST), are different between the first and second eye measured. METHODS: Intraocular pressure and biomechanical parameters were collected from both eyes of healthy participants (N = 139). The ORA measured corneal-compensated intraocular pressure, Goldmann-correlated intraocular pressure, and corneal hysteresis. The CorVis ST measured biomechanically corrected intraocular pressure, stiffness parameter at first applanation, and stiffness parameter at highest concavity. For each measurement, a paired t test compared the value of the first eye measured against that of the second eye measured. RESULTS: For the ORA, Goldmann-correlated intraocular pressure was significantly higher ( P = .001) in the first eye (14.8 [3.45] mmHg) than in the second eye (14.3 [3.63] mmHg). For the CorVis ST, biomechanically corrected intraocular pressure was significantly higher ( P < .001) in the second eye (14.7 [2.14] mmHg) than in the first eye (14.3 [2.11] mmHg). Stiffness parameter at first applanation (intereye difference, 6.85 [9.54] mmHg/mm) was significantly ( P < .001) higher in the first eye than in the second eye. Stiffness parameter at highest concavity was significantly higher ( P = .01) in the second eye (14.3 [3.18] mmHg/mm) than in the first eye (14.0 [3.13] mmHg/mm). CONCLUSIONS: Although there were statistically significant intereye differences in intraocular pressure and in biomechanical parameters for both devices, the variations were small and thus unlikely to affect clinical outcomes.

Blue and Red Light-Evoked Pupil Responses in Photophobic Subjects with TBI.

PURPOSE: Photophobia is a common symptom in individuals suffering from traumatic brain injury (TBI). Recent evidence has implicated blue light-sensitive intrinsically photosensitive retinal ganglion cells (ipRGCs) in contributing to the neural circuitry mediating photophobia in migraine sufferers. The goal of this work is to test the hypothesis that ipRGC function is altered in TBI patients with photophobia by assessing pupillary responses to blue and red light. METHODS: Twenty-four case participants (mean age 43.3; 58% female), with mild TBI and self-reported photophobia, and 12 control participants (mean age 42.6; 58% female) were in this study. After 10 minutes of dark adaptation, blue (470 nm, 1 × 10 phots/s/cm) and red (625 nm, 7 × 10 phots/s/cm) flashing (0.1 Hz) light stimuli were delivered for 30 seconds to the dilated left eye while the right pupil was recorded. The amplitude of normalized pupil fluctuation (constriction and dilation) was quantified using Fourier fast transforms. RESULTS: In both case and control participants, the amplitude of pupil fluctuation was significantly less for the blue light stimuli as compared to the red light stimuli, consistent with a contribution of ipRGCs to these pupil responses. There was no significant difference in the mean pupil fluctuation amplitudes between the two participant groups, but case participants displayed greater variability in their pupil responses to the blue stimulus. CONCLUSIONS: Case and control participants showed robust ipRGC-mediated components in their pupil responses to blue light. The results did not support the hypothesis that ipRGCs are "hypersensitive" to light in TBI participants with photophobia. However, greater pupil response variability in the case subjects suggests that ipRGC function may be more heterogeneous in this group.

Keratoconus cone location influences ocular biomechanical parameters measured by the Ocular Response Analyzer.

BACKGROUND: Keratoconus is characterized by asymmetry in the biomechanical properties of the cornea, with focal weakness in the area of cone formation. We tested the hypothesis that centrally-measured biomechanical parameters differ between corneas with peripheral cones and corneas with central cones. METHODS: Fifty participants with keratoconus were prospectively recruited. The mean ± standard deviation age was 38 ± 13 years. Axial and tangential corneal topography were analyzed in both eyes, if eligible. Cones in the central 3 mm of the cornea were considered central, and cones outside the central 3 mm were considered peripheral. Each eye was then measured with the Ocular Response Analyzer (ORA) tonometer. T-tests compared differences in ORA-generated waveform parameters between cohorts. RESULTS: Seventy-eight eyes were analyzed. According to the axial topography maps, 37 eyes had central cones and 41 eyes had peripheral cones. According to the tangential topography maps, 53 eyes had central cones, and 25 eyes had peripheral cones. For the axial-topography algorithm, wave score (WS) was significantly higher in peripheral cones than central cones (inter-cohort difference = 1.27 ± 1.87). Peripheral cones had a significantly higher area of first peak, p1area (1047 ± 1346), area of second peak, p2area (1130 ± 1478), height of first peak, h1 (102 ± 147), and height of second peak, h2 (102 ± 127), than central cones. Corneal hysteresis (CH), width of the first peak, w1, and width of the second peak, w2, did not significantly differ between cohorts. There were similar results for the tangential-topography algorithm, with a significant difference between the cohorts for p1area (855 ± 1389), p2area (860 ± 1531), h1 (81.7 ± 151), and h2 (92.1 ± 131). CONCLUSIONS: Cone location affects the biomechanical response parameters measured under central loading of the cornea. The ORA delivers its air puff to the central cornea, so the fact that h1 and h2 and that p1area and p2area were smaller in the central cone cohort than in the peripheral cone cohort suggests that corneas with central cones are softer or more compliant centrally than corneas with peripheral cones, which is consistent with the location of the pathology. This result is evidence that corneal weakening in keratoconus is focal in nature and is consistent with localized disruption of lamellar orientation.

Automated vertical cup-to-disc ratio determination from fundus images for glaucoma detection.

Glaucoma is the leading cause of irreversible blindness worldwide. Often asymptomatic for years, this disease can progress significantly before patients become aware of the loss of visual function. Critical examination of the optic nerve through ophthalmoscopy or using fundus images is a crucial component of glaucoma detection before the onset of vision loss. The vertical cup-to-disc ratio (VCDR) is a key structural indicator for glaucoma, as thinning of the superior and inferior neuroretinal rim is a hallmark of the disease. However, manual assessment of fundus images is both time-consuming and subject to variability based on clinician expertise and interpretation. In this study, we develop a robust and accurate automated system employing deep learning (DL) techniques, specifically the YOLOv7 architecture, for the detection of optic disc and optic cup in fundus images and the subsequent calculation of VCDR. We also address the often-overlooked issue of adapting a DL model, initially trained on a specific population (e.g., European), for VCDR estimation in a different population. Our model was initially trained on ten publicly available datasets and subsequently fine-tuned on the REFUGE dataset, which comprises images collected from Chinese patients. The DL-derived VCDR displayed exceptional accuracy, achieving a Pearson correlation coefficient of 0.91 (P = 4.12 × 10-412) and a mean absolute error (MAE) of 0.0347 when compared to assessments by human experts. Our models also surpassed existing approaches on the REFUGE dataset, demonstrating higher Dice similarity coefficients and lower MAEs. Moreover, we developed an optimization approach capable of calibrating DL results for new populations. Our novel approaches for detecting optic discs and optic cups and calculating VCDR, offers clinicians a promising tool that significantly reduces manual workload in image assessment while improving both speed and accuracy. Most importantly, this automated method effectively differentiates between glaucoma and non-glaucoma cases, making it a valuable asset for glaucoma detection.

Corneal Stress Distribution Evolves from Thickness-Driven in Normal Corneas to Curvature-Driven with Progression in Keratoconus.

Purpose: To introduce the novel parameter of Corneal Contribution to Stress (CCS) and compare stress distribution patterns between keratoconus (KCN) and normal corneas. Design: Prospective, observational, cross-sectional study. Participants: The study included 66 eyes of 40 subjects diagnosed with KCN and 155 left eyes from 155 normal control (NRL) subjects. Methods: Tomography was obtained to calculate the newly proposed CCS, defined according to the hoop stress formula without intraocular pressure, R/2t, where R is the radius of curvature and t is the thickness. CCS maps were calculated from pachymetry and tangential curvature maps. Custom software identified the 2-mm-diameter zones of greatest curvature (Cspot-max), thinnest pachymetry (Pach-min), greatest stress (CCSmax), and lowest stress (CCSmin). Stress difference (CCSdiff) was calculated as CCSmax - CCSmin. Distances between Cspot-max vs. Pach-min, vs. CCSmax, and vs. CCSmin, as well as between Pach-min vs. CCSmax and vs. CCSmin, were calculated. t tests were performed between cohorts, and paired t tests were performed within cohorts. Univariate linear regression analyses were performed between parameters and distances. The significance threshold was P < 0.05. Main Outcome Measures: Corneal stress parameters, corneal features of maximum curvature, minimum thickness, and distances between corneal stress parameters and corneal features. Results: CCSmax was significantly closer to Pach-min (0.79 ± 0.92) and Cspot-max (2.04 ± 0.85) than CCSmin (3.17 ± 0.38, 2.73 ± 1.53, respectively) in NRL, P < 0.0001, whereas CCSmin was significantly closer to Cspot-max (1.35 ± 1.43) than CCSmax (2.52 ± 0.72) in KCN, P < 0.0001. Cspot-max (severity) was significantly related to CCSdiff in KCN (P < 0.0001; R2 = 0.5882) with a weak relationship in NRL (P < 0.0080, R2 = 0.0451). Cspot-max was significantly related to the distance from Pach-min to CCSmax (P < 0.0001; R2 = 0.3737) without significance in NRL (P = 0.8011). Conclusions: Corneal stress is driven by thickness in NRL, with greatest stress at thinnest pachymetry and greatest curvature. However, maximum stress moves away from thinnest pachymetry with progression in KCN, and minimum stress is associated with maximum curvature. Severity in KCN is significantly related to greater difference between maximum and minimum stress, consistent with the biomechanical cycle of decompensation. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Henle fiber layer thickening and deficits in objective retinal function in participants with a history of multiple traumatic brain injuries.

Introduction: This study tested whether multiple traumatic brain injuries (TBIs) alter the structure of the Henle fiber layer (HFL) and degrade cell-specific function in the retinas of human participants. Methods: A cohort of case participants with multiple TBIs and a cohort of pair-matched control participants were prospectively recruited. Directional optical coherence tomography and scanning laser polarimetry measured HFL thickness and phase retardation, respectively. Full-field flash electroretinography (fERG) assessed retinal function under light-adapted (LA) 3.0, LA 30 Hz, dark-adapted (DA) 0.01, DA 3.0, and DA 10 conditions. Retinal imaging and fERG outcomes were averaged between both eyes, and paired t-tests or Wilcoxon signed-rank tests analyzed inter-cohort differences. Results: Global HFL thickness was significantly (p = 0.02) greater in cases (8.4 ± 0.9 pixels) than in controls (7.7 ± 1.1 pixels). There was no statistically significant difference (p = 0.91) between the cohorts for global HFL phase retardation. For fERG, LA 3.0 a-wave amplitude was significantly reduced (p = 0.02) in cases (23.5 ± 4.2 µV) compared to controls (29.0 ± 8.0 µV). There were no other statistically significant fERG outcomes between the cohorts. Discussion: In summary, the HFL thickens after multiple TBIs, but phase retardation remains unaltered in the macula. Multiple TBIs may also impair retinal function, indicated by a reduction in a-wave amplitude. These results support the potential of the retina as a site to detect TBI-associated pathology.

Clinical Ocular Biomechanics: Where Are We after 20 Years of Progress?

Purpose: Ocular biomechanics is an assessment of the response of the structures of the eye to forces that may lead to disease development and progression, or influence the response to surgical intervention. The goals of this review are (1) to introduce basic biomechanical principles and terminology, (2) to provide perspective on the progress made in the clinical study and assessment of ocular biomechanics, and (3) to highlight critical studies conducted in keratoconus, laser refractive surgery, and glaucoma in order to aid interpretation of biomechanical parameters in the laboratory and in the clinic.Methods: A literature review was first conducted of basic biomechanical studies related to ocular tissue. The subsequent review of ocular biomechanical studies was limited to those focusing on keratoconus, laser refractive surgery, or glaucoma using the only two commercially available devices that allow rapid assessment of biomechanical response in the clinic.Results: Foundational studies on ocular biomechanics used a combination of computer modeling and destructive forces on ex-vivo tissues. The knowledge gained from these studies could not be directly translated to clinical research and practice until the introduction of non-contact tonometers that quantified the deformation response of the cornea to an air puff, which represents a non-destructive, clinically appropriate load. The corneal response includes a contribution from the sclera which may limit corneal deformation. Two commercial devices are available, the Ocular Response Analyzer which produces viscoelastic parameters with a customized load for each eye, and the Corvis ST which produces elastic parameters with a consistent load for every eye. Neither device produces the classic biomechanical properties reported in basic studies, but rather biomechanical deformation response parameters which require careful interpretation.Conclusions: Research using clinical tools has enriched our understanding of how ocular disease alters ocular biomechanics, as well as how ocular biomechanics may influence the pathophysiology of ocular disease and response to surgical intervention.

Foveal Phase Retardation Correlates With Optically Measured Henle Fiber Layer Thickness.

This study quantified and compared phase retardation distribution in the central macula with the thickness of the Henle fiber layer (HFL). A scanning laser polarimeter (SLP) was used to acquire 20° × 40° macular-centered images, either with fixed corneal compensation or with variable corneal compensation, in two cohorts of clinically normal subjects (N = 36). Phase retardation maps from SLP imaging were used to generate a macular cross pattern (fixed compensation) or an annulus pattern (variable compensation) centered on the macula. Intensity profiles in the phase retardation maps were produced using annular regions of interest at eccentricities from 0.25° to 3°. Pixel intensity was averaged at each eccentricity, acting as a surrogate for macular phase retardation. Directional OCT images were acquired in the horizontal and vertical meridians in all subjects, allowing visualization of the HFL thickness. HFL thickness was manually segmented in each meridian and averaged. In both cohorts, phase retardation and HFL thickness were highly correlated in the central 3° assessed, providing further evidence that the source of the phase retardation signal in the central macula is dominated by the HFL and that the center of the macula on cross sectional imaging corresponds closely with the center of the macular cross on SLP imaging.

Structure and function of retinal ganglion cells in subjects with a history of repeated traumatic brain injury.

This study tested whether repeated traumatic brain injuries (TBIs) alter the objective structure or the objective function of retinal ganglion cells (RGCs) in human subjects recruited from an optometry clinic. Case subjects (n = 25) with a history of repeated TBIs (4.12 ± 2.76 TBIs over 0-41 years) and healthy pair-matched control subjects (n = 30) were prospectively recruited. Retinal nerve fiber layer (RNFL) thickness was quantified with spectral-domain optical coherence tomography, and scanning laser polarimetry measured RNFL phase retardation. Measurements of the photopic negative response were made using full-field flash electroretinography. There was no statistically significant difference (p = 0.42) in global RNFL thickness between the case cohort (96.6 ± 9.4 microns) and the control cohort (94.9 ± 7.0 microns). There was no statistically significant difference (p = 0.80) in global RNFL phase retardation between the case cohort (57.9 ± 5.7 nm) and the control cohort (58.2 ± 4.6 nm). There were no statistically significant differences in the peak time (p = 0.95) of the PhNR or in the amplitude (p = 0.11) of the PhNR between the case cohort (69.9 ± 6.9 ms and 24.1 ± 5.1 µV, respectively) and the control cohort (70.1 ± 8.9 ms and 27.8 ± 9.1 µV, respectively). However, PhNR amplitude was more variable (p < 0.025) in the control cohort than in the case cohort. Within the case cohort, there was a strong positive (r = 0.53), but not statistically significant (p = 0.02), association between time since last TBI and PhNR amplitude. There was also a modest positive (r = 0.45), but not statistically significant (p = 0.04), association between time since first TBI and PhNR amplitude. Our results suggest that there were no statistically significant differences in the objective structure or in the objective function of RGCs between the case cohort and the control cohort. Future large, longitudinal studies will be necessary to confirm our negative results and to more fully investigate the potential interaction between PhNR amplitude and time since first or last TBI.

Observer-perceived light aversion behaviour in photophobic subjects with traumatic brain injury.

BACKGROUND: Photophobia is a common sequela of traumatic brain injury (TBI). Diagnostic tools for this debilitating condition are lacking. This investigation sought to determine whether masked observers can distinguish subjects with TBI-associated photophobia from matched controls based on video recordings of their ocular responses to light stimulation. METHODS: Cohorts of students (n = 20), photophobic TBI subjects (n = 28) and their matched control subjects (n = 12) were recruited. A custom pupillometer delivered bright (1013 -1014 photons/s/cm2 ), flashing (0.10 Hz) red (625 nm) and blue (470 nm) light stimuli to subjects, and consensual pupil light responses were recorded. Using a five-point scale, masked observers later graded light aversion behaviour in the pupil video recordings obtained from the student cohort based on observed blinking, tearing and squinting. A grading scale was developed and used by masked observers to grade light aversion behaviour in videos obtained from subjects with post-TBI photophobia and the matched controls. These subjects also scored their perceived discomfort during each light pulse using a five-point scale. RESULTS: The subjects in the TBI cohort scored both the blue and red flashing stimuli as evoking more discomfort, relative to control subjects, consistent with their reported photophobia. There was strong agreement among the masked observers for their grades of light aversion behaviour in the videos of ocular light stimulation (interclass correlation co-efficient = 0.78; 29 per cent perfect concordance). However, the median grades for the videos obtained from the TBI subject cohort were not significantly different from those for the control group. CONCLUSIONS: Clinicians cannot diagnose TBI-related photophobia based solely on video recordings of ocular responses to light. The need remains for an objective test to diagnose and manage this prevalent post-TBI symptom.