Eye movements in patients with post-COVID condition.

Eye movement control is impaired in some neurological conditions, but the impact of COVID-19 on eye movements remains unknown. This study aims to investigate differences in oculomotor function and pupil response in individuals who suffer post-COVID-19 condition (PCC) with cognitive deficits. Saccades, smooth pursuit, fixation, vergence and pupillary response were recorded using an eye tracker. Eye movements and pupil response parameters were computed. Data from 16 controls, 38 COVID mild (home recovery) and 19 COVID severe (hospital admission) participants were analyzed. Saccadic latencies were shorter in controls (183 ± 54 ms) than in COVID mild (236 ± 83 ms) and COVID severe (227 ± 42 ms) participants (p = 0.017). Fixation stability was poorer in COVID mild participants (Bivariate Contour Ellipse Area of 0.80 ± 1.61°2 vs 0.36 ± 0.65 °2 for controls, p = 0.019), while percentage of pupil area reduction/enlargement was reduced in COVID severe participants (39.7 ± 12.7%/31.6 ± 12.7% compared to 51.7 ± 22.0%/49.1 ± 20.7% in controls, p < 0.015). The characteristics of oculomotor alterations found in PCC may be useful to understand different pathophysiologic mechanisms.

Influence of power and the time of application of fogging lenses on accommodation.

Fogging is a non-invasive technique based on the use of positive spherical power lenses to relax accommodation during refraction that is commonly used as an alternative to cycloplegic drugs. Although the mechanism of the fogging technique has been described, some aspects of its methodology remain unclear. The main purpose of this work was to determine which lens power and time of application are more suitable for achieving a successful relaxation of accommodation by analyzing the changes in accommodation when fogging lenses of different powers were placed in front of the participants' eye for a certain timespan. The results of this analysis showed, in general, that low-power lenses and timespans of less than half a minute provided the highest relaxation of accommodation. However, high inter-subject variability was found in the two variables (power and time).

Membrane Protein Detection and Morphological Analysis of Red Blood Cells in Hereditary Spherocytosis by Confocal Laser Scanning Microscopy.

In hereditary spherocytosis (HS), genetic mutations in the cell membrane and cytoskeleton proteins cause structural defects in red blood cells (RBCs). As a result, cells are rigid and misshapen, usually with a characteristic spherical form (spherocytes), too stiff to circulate through microcirculation regions, so they are prone to undergo hemolysis and phagocytosis by splenic macrophages. Mild to severe anemia arises in HS, and other derived symptoms like splenomegaly, jaundice, and cholelithiasis. Although abnormally shaped RBCs can be identified under conventional light microscopy, HS diagnosis relies on several clinical factors and sometimes on the results of complex molecular testing. It is specially challenging when other causes of anemia coexist or after recent blood transfusions. We propose two different approaches to characterize RBCs in HS: (i) an immunofluorescence assay targeting protein band 3, which is affected in most HS cases and (ii) a three-dimensional morphology assay, with living cells, staining the membrane with fluorescent dyes. Confocal laser scanning microscopy (CLSM) was used to carry out both assays, and in order to complement the latter, a software was developed for the automated detection of spherocytes in blood samples. CLSM allowed the precise and unambiguous assessment of cell shape and protein expression.

System for Objective Assessment of the Accommodation Response During Subjective Refraction.

Purpose: To evaluate a system based on a Hartmann-Shack wavefront sensor attached to a phoropter that allows the user to obtain real-time information about the refractive state of the eye and the accommodation response (AR). Methods: The objective refractions (ME) and ARs of 73 subjects (50 women, 23 men; ages, 19-69 years) were assessed with the system developed while placing in the phoropter the subjective refraction (MS) plus a set of trial lenses with differences in spherical equivalent power (ΔM) between ±2 diopters (D). Results: The objective estimations (ME) showed a good correlation with the subjective values (MS) (r = 0.989; P < 0.001). The means of the ARs presented a region where the accommodation remained stable (ΔM from +2 D to about 0 D), followed by another in which the response increased progressively (ΔM from about 0 to -2 D) with the magnitude of the accommodation stimulus. The analysis of variance within subjects applied to ARs introducing age and MS as covariates showed an increasing effect size of age from medium to large between ΔM of -0.5 and -2 D. In contrast, MS had a medium effect size (between ΔM of +2 and 0 D). Conclusions: The implemented system permitted an objective estimation of the refraction of the eye and its AR. Because it is coupled to a phoropter, the system can be used to retrieve the AR during subjective refraction procedures. Translational Relevance: The developed system can be used as a supporting tool during subjective refraction to provide certainty about the true state of accommodation.

Reflectance evaluation of eye fundus structures with a visible and near-infrared multispectral camera.

We examined the spectral reflectance of fundus structures in the visible and near-infrared (400-1300 nm) range for contributing to the medical diagnosis of fundus diseases. Spectral images of healthy eye fundus and other ocular diseases were acquired using a novel multispectral fundus camera. Reflectance metrics were computed based on contrast to analyze the spectral features. Significant differences were observed among the structures in healthy and diseased eye fundus. Specifically, near-infrared analysis allows imaging of deeper layers, such as the choroid, which, to date, has not been retrieved using traditional color fundus cameras. Pathological structures, which were hardly observable in color fundus images owing to metamerism, were also revealed by the developed multispectral fundus camera.

Optical Technologies for the Improvement of Skin Cancer Diagnosis: A Review.

The worldwide incidence of skin cancer has risen rapidly in the last decades, becoming one in three cancers nowadays. Currently, a person has a 4% chance of developing melanoma, the most aggressive form of skin cancer, which causes the greatest number of deaths. In the context of increasing incidence and mortality, skin cancer bears a heavy health and economic burden. Nevertheless, the 5-year survival rate for people with skin cancer significantly improves if the disease is detected and treated early. Accordingly, large research efforts have been devoted to achieve early detection and better understanding of the disease, with the aim of reversing the progressive trend of rising incidence and mortality, especially regarding melanoma. This paper reviews a variety of the optical modalities that have been used in the last years in order to improve non-invasive diagnosis of skin cancer, including confocal microscopy, multispectral imaging, three-dimensional topography, optical coherence tomography, polarimetry, self-mixing interferometry, and machine learning algorithms. The basics of each of these technologies together with the most relevant achievements obtained are described, as well as some of the obstacles still to be resolved and milestones to be met.

Spectroscopic Evaluation of Red Blood Cells of Thalassemia Patients with Confocal Microscopy: A Pilot Study.

Hemoglobinopathies represent the most common single-gene defects in the world and pose a major public health problem, particularly in tropical countries, where they occur with high frequency. Diagnosing hemoglobinopathies can sometimes be difficult due to the coexistence of different causes of anemia, such as thalassemia and iron deficiency, and blood transfusions, among other factors, and requires expensive and complex molecular tests. This work explores the possibility of using spectral confocal microscopy as a diagnostic tool for thalassemia in pediatric patients, a disease caused by mutations in the globin genes that result in changes of the globin chains that form hemoglobin-in pediatric patients. Red blood cells (RBCs) from patients with different syndromes of alpha-thalassemia and iron deficiency (including anemia) as well as healthy (control) subjects were analyzed under a Leica TCS SP8 confocal microscope following different image acquisition protocols. We found that diseased RBCs exhibited autofluorescence when excited at 405 nm and their emission was collected in the spectral range from 425 nm to 790 nm. Three experimental descriptors calculated from the mean emission intensities at 502 nm, 579 nm, 628 nm, and 649 nm allowed us to discriminate between diseased and healthy cells. According to the results obtained, spectral confocal microscopy could serve as a tool in the diagnosis of thalassemia.

Experimental characterization of the speckle pattern at the output of a multimode optical fiber.

Speckle patterns produced by coherent waves interfering with each other are undesirable in many imaging applications (for example, in laser projection systems) but on the other hand, they contain useful information that can be exploited (for example, for blood flow analysis or reconstruction of the object that generates the speckle). It is therefore important to understand how speckle can be enhanced or reduced by tailoring the coherence of laser light. Using a conventional semiconductor laser and a multimode optical fiber we study experimentally how the speckle pattern depends on the laser pump current and on the image acquisition settings. By varying the pump current from below to above the lasing threshold, and simultaneously tuning the image exposure time to compensate for the change in brightness, we find conditions that allow for recorded images with similar average intensity, but with speckle contrast (the standard deviation of the intensity over the average intensity) as low as 0.16, or as high as 0.99.

Fast visible and extended near-infrared multispectral fundus camera.

We present a multispectral fundus camera that performs fast imaging of the ocular posterior pole in the visible and near-infrared (400 to 1300 nm) wavelengths through 15 spectral bands, using a flashlight source made of light-emitting diodes, and CMOS and InGaAs cameras. We investigate the potential of this system for visualizing occult and overlapping structures of the retina in the unexplored wavelength range beyond 900 nm, in which radiation can penetrate deeper into the tissue. Reflectance values at each pixel are also retrieved from the acquired images in the analyzed spectral range. The available spectroscopic information and the visualization of retinal structures, specifically the choroidal vasculature and drusen-induced retinal pigment epithelium degeneration, which are hardly visible in conventional color fundus images, underline the clinical potential of this system as a new tool for ophthalmic diagnosis.

Method to reduce undesired multiple fundus scattering effects in double-pass systems.

Double-pass systems rely on backscattering of light by the human ocular fundus to assess the optical quality of the eye. In this work, we present a method to reduce double-pass image degradation caused by undesired multiple scattering effects in the eye fundus. The reduction is based on combined data processing of simultaneous measurements using two different configurations: one symmetric with equal entrance and exit pupils and another asymmetric with unequal entrance and exit pupils. Under certain conditions, such scattering effects may be effectively suppressed. Measurements of human eyes show that, although multiple fundus scattering imposes a shift on the estimations, double-pass systems can be used to predict the optical quality of the eye within a population.

Quantification of forward scattering based on the analysis of double-pass images in the frequency domain.

PURPOSE: To assess forward intraocular scattering by means of a new parameter (Frequency Scatter Index, FSI3 ) based on the analysing double-pass retinal images in the frequency domain, which minimizes the impact of aberrations on the results. METHODS: A prospective observational study was carried out in the Department of Ophthalmology, Hospital Universitari Mútua de Terrassa (Spain) on a group of 19 patients diagnosed with nuclear cataracts of various LOCSIII grades and a control group (CG) with nine healthy eyes. We recorded double-pass retinal images with a custom set-up based on a high-sensitivity digital camera. The FSI3 was then computed using spatial frequencies below three cycles per degree. A preliminary validation of the FSI3 was performed on an artificial eye and two eyes of volunteers with and without commercial diffusers, and under defocus. RESULTS: The FSI3 was hardly affected by defocus values up to 2.50 D. The mean (and standard deviation) FSI3 values were as follows: for the CG, 1.19 (0.21); and for LOCSIII grades nuclear opacity 1, 2 and 3, 1.30 (0.12), 1.62 (0.21) and 1.85 (0.21), respectively. Eyes with cataracts showed FSI3 values significantly different than healthy eyes (p = 0.001). A good correlation (ρ = 0.861, p < 0.001) was found between the FSI3 and objective scatter index provided by a commercial instrument. CONCLUSION: Since aberrations have little impact on the FSI3 , the light scatter assessment becomes less dependent on the patient's refractive error compensation and the presence of higher-order aberrations. The FSI3 can further the clinical and scientific understanding of forward intraocular scattering.

Speckle reduction in double-pass retinal images.

The double pass (DP) technique quantifies the optical quality of the eye by measuring its point spread function. The low reflectivity of the retina requires the use of a high-brightness, point-like illumination source, and thus, DP systems use laser diodes (LDs). However, LDs light produces speckle, and a low-cost solution to reduce speckle is to include a vibrating mirror in the beam path. With the goal of finding an all-optical solution, here we perform a comparative study of the amount of speckle produced by three semiconductor light sources: an LD, a light emitting diode (LED), and a superluminescent diode (SLED). We also compare the results with the speckle reduction that is obtained with a vibrating mirror. We find that the SLED is a good alternative to LD illumination, as the amount of speckle in the image is almost as low as that obtained with an LD and a vibrating mirror in the beam path.

System based on the contrast of Purkinje images to measure corneal and lens scattering.

Current methods to measure intraocular scattering provide information on the total scattered light, which consists of the combined contributions originating from different ocular structures. In this work, we propose a technique for the objective and independent assessment of scattering caused by the cornea and the lens based on the analysis of the contrast of the third and fourth Purkinje images. The technique is preliminarily validated first by using artificial eyes with different levels of corneal and lens scattering; second, it is validated in eyes wearing customized contact lenses to simulate corneal scattering and eyes with nuclear cataracts. Finally, it is tested on a larger population of eyes with cataracts and corneal disorders to prove its clinical usefulness.

Visible and Extended Near-Infrared Multispectral Imaging for Skin Cancer Diagnosis.

With the goal of diagnosing skin cancer in an early and noninvasive way, an extended near infrared multispectral imaging system based on an InGaAs sensor with sensitivity from 995 nm to 1613 nm was built to evaluate deeper skin layers thanks to the higher penetration of photons at these wavelengths. The outcomes of this device were combined with those of a previously developed multispectral system that works in the visible and near infrared range (414 nm⁻995 nm). Both provide spectral and spatial information from skin lesions. A classification method to discriminate between melanomas and nevi was developed based on the analysis of first-order statistics descriptors, principal component analysis, and support vector machine tools. The system provided a sensitivity of 78.6% and a specificity of 84.6%, the latter one being improved with respect to that offered by silicon sensors.

Validation of a gonio-hyperspectral imaging system based on light-emitting diodes for the spectral and colorimetric analysis of automotive coatings.

In this study, a novel gonio-hyperspectral imaging system based on light-emitting diodes for the analysis of automotive coatings was validated colorimetrically and spectrally from 368 to 1309 nm. A total of 30 pearlescent, 30 metallic, and 30 solid real automotive coatings were evaluated with this system, the BYK-mac and X-Rite MA98 gonio-spectrophotometers, and also with the SPECTRO 320 spectrometer for further comparison. The results showed very precise correlations, especially in the visible range. In conclusion, this new system provides a deeper assessment of goniochromatic pigments than current approaches due to the expansion of the spectral range to the infrared.

Multispectral imaging system based on light-emitting diodes for the detection of melanomas and basal cell carcinomas: a pilot study (erratum).

This erratum corrects the error of an omitted author in doi: http://dx.doi.org/10.1117/1.JBO.22.6.065006

Multispectral imaging system based on light-emitting diodes for the detection of melanomas and basal cell carcinomas: a pilot study.

This article proposes a multispectral system that uses the analysis of the spatial distribution of color and spectral features to improve the detection of skin cancer lesions, specifically melanomas and basal cell carcinomas. The system consists of a digital camera and light-emitting diodes of eight different wavelengths (414 to 995 nm). The parameters based on spectral features of the lesions such as reflectance and color, as well as others empirically computed using reflectance values, were calculated pixel-by-pixel from the images obtained. Statistical descriptors were calculated for every segmented lesion [mean ( x ˜ ), standard deviation ( σ ), minimum, and maximum]; descriptors based on the first-order statistics of the histogram [entropy ( E p ), energy ( E n ), and third central moment ( µ 3 )] were also obtained. The study analyzed 429 pigmented and nonpigmented lesions: 290 nevi and 139 malignant (95 melanomas and 44 basal cell carcinomas), which were split into training and validation sets. Fifteen parameters were found to provide the best sensitivity (87.2% melanomas and 100% basal cell carcinomas) and specificity (54.5%). The results suggest that the extraction of textural information can contribute to the diagnosis of melanomas and basal cell carcinomas as a supporting tool to dermoscopy and confocal microscopy.

Spherical subjective refraction with a novel 3D virtual reality based system / Refracción subjetiva esférica utilizando un nuevo sistema 3D basado en realidad virtual

Purpose: To conduct a clinical validation of a virtual reality-based experimental system that is able to assess the spherical subjective refraction simplifying the methodology of ocular refraction. Methods: For the agreement assessment, spherical refraction measurements were obtained from 104 eyes of 52 subjects using three different methods: subjectively with the experimental prototype (Subj.E) and the classical subjective refraction (Subj.C); and objectively with the WAM-5500 autorefractor (WAM). To evaluate precision (intra- and inter-observer variability) of each refractive tool independently, 26 eyes were measured in four occasions. Results: With regard to agreement, the mean difference (±SD) for the spherical equivalent (M) between the new experimental subjective method (Subj.E) and the classical subjective refraction (Subj.C) was −0.034 D (±0.454 D). The corresponding 95% Limits of Agreement (LoA) were (−0.856 D, 0.924 D). In relation to precision, intra-observer mean difference for the M component was 0.034 ± 0.195 D for the Subj.C, 0.015 ± 0.177 D for the WAM and 0.072 ± 0.197 D for the Subj.E. Inter-observer variability showed worse precision values, although still clinically valid (below 0.25 D) in all instruments. Conclusions: The spherical equivalent obtained with the new experimental system was precise and in good agreement with the classical subjective routine. The algorithm implemented in this new system and its optical configuration has been shown to be a first valid step for spherical error correction in a semiautomated way (AU)

Objetivo: Realizar una validación clínica de un sistema experimental basado en realidad virtual, capaz de evaluar la refracción subjetiva esférica simplificando la metodología de la refracción ocular. Métodos: Para evaluar la concordancia, se obtuvieron mediciones de la refracción esférica de 104 ojos pertenecientes a 52 sujetos, utilizando tres métodos diferentes: subjetivamente con el prototipo experimental (Subj.E) y la refracción subjetiva clásica (Subj.C); y objetivamente con el autorrefractómetro WAM-5500 (WAM). Para evaluar la precisión (variabilidad intra e inter-observador) de cada herramienta refractiva, de forma independiente, se midieron 26 ojos en cuatro ocasiones. Resultados: Con respecto a la concordancia, la diferencia media (±DE) para el equivalente esférico (M) entre el nuevo método subjetivo experimental (Subj.E) y la refracción subjetiva clásica (Subj.C) fue de −0,034 D (±0,454 D). El 95% correspondiente a los Límites de la Concordancia (LoA) fue de (−0,856 D, 0,924 D). En relación a la precisión, la diferencia media intra observador para el componente M fue de 0,034 ± 0,195 D para Subj.C, 0,015 ± 0,177 D para WAM y 0,072 ± 0,197 D para Subj.E. La variabilidad inter observador reflejó peores valores de precisión, aunque fueron clínicamente válidos (inferiores a 0,25 D) en todos los instrumentos. Conclusiones: El equivalente esférico obtenido con el nuevo sistema experimental fue preciso y guardó consonancia con la rutina subjetiva clásica. El algoritmo introducido en este nuevo sistema, y su configuración óptica, han demostrado ser un avance válido para la corrección del error esférico de modo semi-automático (AU)

Spherical subjective refraction with a novel 3D virtual reality based system.

PURPOSE: To conduct a clinical validation of a virtual reality-based experimental system that is able to assess the spherical subjective refraction simplifying the methodology of ocular refraction. METHODS: For the agreement assessment, spherical refraction measurements were obtained from 104 eyes of 52 subjects using three different methods: subjectively with the experimental prototype (Subj.E) and the classical subjective refraction (Subj.C); and objectively with the WAM-5500 autorefractor (WAM). To evaluate precision (intra- and inter-observer variability) of each refractive tool independently, 26 eyes were measured in four occasions. RESULTS: With regard to agreement, the mean difference (±SD) for the spherical equivalent (M) between the new experimental subjective method (Subj.E) and the classical subjective refraction (Subj.C) was -0.034D (±0.454D). The corresponding 95% Limits of Agreement (LoA) were (-0.856D, 0.924D). In relation to precision, intra-observer mean difference for the M component was 0.034±0.195D for the Subj.C, 0.015±0.177D for the WAM and 0.072±0.197D for the Subj.E. Inter-observer variability showed worse precision values, although still clinically valid (below 0.25D) in all instruments. CONCLUSIONS: The spherical equivalent obtained with the new experimental system was precise and in good agreement with the classical subjective routine. The algorithm implemented in this new system and its optical configuration has been shown to be a first valid step for spherical error correction in a semiautomated way.

Comparison of the Adaptive Optics Vision Analyzer and the KR-1 W for measuring ocular wave aberrations.

BACKGROUND: The aim was to assess the agreement in the measurement of ocular aberrations between a new Adaptive Optics Vision Analyzer (AOVA, Voptica, Murcia, Spain) and a commercial aberrometer (KR-1 W, Topcon, Tokyo, Japan), both based on the Hartmann-Shack technique. METHODS: One experienced examiner measured 29 healthy right eyes nine consecutive times with the two instruments. The individual Zernike coefficients and the root mean square (RMS) of each order from the second to the fifth order, the higher-order RMS (RMSHOA ), the total RMS (RMSTOT ) and the values of the spherical equivalent (M) and Jackson cross-cylinder (J0 and J45 ) were compared. All aberrations were computed for a 4.0 mm pupil diameter. RESULTS: Bland and Altman analysis showed good agreement between instruments and most of the parameters showed no statistically significant differences. Although the largest mean differences were obtained for the defocus coefficient C(2,0) and the spherical equivalent (M) with a mean difference (and standard deviation) of 0.190 ± 0.099 µm and -0.150 ± 0.188 D, respectively, they were clinically acceptable and significant correlations were found between the AOVA and KR-1 W for the major refractive components such as spherical equivalent (r = 0.995, p < 0.001), J0 (r = 0.964, p < 0.001), J45 (r = 0.901, p < 0.001) and C(4,0) (r = 0.575, p = 0.001). CONCLUSION: The results suggest good agreement between instruments. Accommodation and misalignment of the measurements may play a role in some of the statistically significant differences that were obtained, specifically for defocus C(2,0), vertical coma C(3,-1) and spherical aberration C(4,0) coefficients; however, these differences were clinically irrelevant.