Disconjugacy of Eye Movements during Attempted Fixation: A Sufficient Marker for Amblyopia?

BACKGROUND: To investigate whether detection of disconjugacy of eye movements during attempted fixation, or interocular position instability, may serve as a single sensitive test for amblyopia. PATIENTS/METHODS AND MATERIAL: Binocular eye movements were recorded at 500 Hz using the EyeLink 1000 eye tracker (SR Research Ltd., Kanata, Ontario, Canada) and analyzed using EyeLink software and Matlab (MathWorks, Natick, MA, USA). Eight subjects (four amblyopes, one successfully treated amblyope, and three non-amblyopes: 7 - 44 years) were asked to fixate on a stationary cross subtending 0.5° at 57 cm. Interocular position instability was quantified by calculating the minimum area bivariate contour ellipse (BCEA) encompassing 68% of the difference between right and left eye position points during 20-second viewing epochs. For statistical analysis, BCEA values, as well as visual acuity and stereoacuity, were normalized by base-10 logarithm transformation. RESULTS: The amblyopic subjects with persistent vision loss (one anisometropic, two strabismic, one deprivation; uncorrected visual acuity range 20/60 - 20/300, corrected stereoacuity range nil-400 arcsec) showed significantly higher interocular position instability (larger 68% BCEAs) than the non-amblyopic subjects (uncorrected visual acuity range 20/20 - 20/800, corrected stereoacuities of 20 arcsec) and the successfully treated strabismic amblyope (to the 20/20 level of visual acuity and 70 arcsec of stereoacuity) during binocular viewing trials; p < 0.01. Interocular position stability was strongly correlated with stereoacuity (in that better stereoacuity was associated with lower 68% BCEAs; r = 0.95), but not with visual acuity (r = 0.20). CONCLUSION: Interocular position instability appears to differentiate amblyopic from non-amblyopic subjects and appears to improve after successful treatment. Interocular position instability may therefore prove to be a single sensitive test for the presence of amblyopia. As a difference measure, it is inherently less susceptible to head motion and calibration error, as well as to conjugate eye motion, and as such is expected to be somewhat immune to latent nystagmus. Interocular position instability may also be useful to guide treatment, especially in preverbal children, and to assess the efficacy of novel treatments. Further research is required to establish optimal interocular position instability thresholds and to determine how specific this measure is to amblyopia.

Computer-aided fixation detection using retinal birefringence in multi-modal ophthalmic systems: Computer, electronics, algorithms.

Many diagnostic and some therapeutic ophthalmic devices require a reliable complementing method to track the direction of gaze or just to validate fixation of the eye on a presented target. This would allow acquisition of artefact-free robust images of the fovea and the surrounding macula. So far, there have been only few attempts to provide fast and dependable fixation information to an optical imaging system in real time, to guide image acquisition. The author's lab has developed several instruments that detect the location of the fovea using retinal birefringence scanning (RBS), proven to be very effective. Here, an RBS-based fixation detection subsystem is proposed, designed to operate conjointly with a number of ophthalmic imaging technologies. Combining RBS with such technologies is not trivial, because RBS uses polarized light and polarization-sensitive optics, while most other modalities don't. The polarization optics was optimized by means of enhanced computer modeling. Both the electronic hardware and the software were designed for fast and reliable performance. Because many retinal imaging systems are used in pediatric settings, extensive audio-visual circuitry was employed for efficient attention/fixation attraction. The optomechanics has been optimized for robust data acquisition. This computer-aided conjoint system employs true anatomical information from the back of the eye and needs no calibration. The prototype instrument uses a decision-making logic based on four frequencies generated during scanning. The results reveal the applicability of RBS as an adjunct fixation monitoring modality, showing promise to remove the limitation imposed by eye movements upon advanced ophthalmic imaging technologies.

Detecting central fixation by means of artificial neural networks in a pediatric vision screener using retinal birefringence scanning.

BACKGROUND: Reliable detection of central fixation and eye alignment is essential in the diagnosis of amblyopia ("lazy eye"), which can lead to blindness. Our lab has developed and reported earlier a pediatric vision screener that performs scanning of the retina around the fovea and analyzes changes in the polarization state of light as the scan progresses. Depending on the direction of gaze and the instrument design, the screener produces several signal frequencies that can be utilized in the detection of central fixation. The objective of this study was to compare artificial neural networks with classical statistical methods, with respect to their ability to detect central fixation reliably. METHODS: A classical feedforward, pattern recognition, two-layer neural network architecture was used, consisting of one hidden layer and one output layer. The network has four inputs, representing normalized spectral powers at four signal frequencies generated during retinal birefringence scanning. The hidden layer contains four neurons. The output suggests presence or absence of central fixation. Backpropagation was used to train the network, using the gradient descent algorithm and the cross-entropy error as the performance function. The network was trained, validated and tested on a set of controlled calibration data obtained from 600 measurements from ten eyes in a previous study, and was additionally tested on a clinical set of 78 eyes, independently diagnosed by an ophthalmologist. RESULTS: In the first part of this study, a neural network was designed around the calibration set. With a proper architecture and training, the network provided performance that was comparable to classical statistical methods, allowing perfect separation between the central and paracentral fixation data, with both the sensitivity and the specificity of the instrument being 100%. In the second part of the study, the neural network was applied to the clinical data. It allowed reliable separation between normal subjects and affected subjects, its accuracy again matching that of the statistical methods. CONCLUSION: With a proper choice of a neural network architecture and a good, uncontaminated training data set, the artificial neural network can be an efficient classification tool for detecting central fixation based on retinal birefringence scanning.

A no-moving-parts sensor for the detection of eye fixation using polarised light and retinal birefringence information.

Polarised near-infra-red light is reflected from the foveal area in a detectable bow-tie pattern of polarisation states, offering the opportunity for eye tracking. A coaxial optical transducer was developed, consisting of a laser diode, a polariser, a filter, and a photodetector. Several such transducers may be used to interrogate different spots on the retina, thus eliminating the requirement for scanning systems with moving parts. To test the signal quality obtainable, using just one transducer, a test subject was asked to fixate successively on twelve targets located on a circle around the transducer, to simulate the retina's being interrogated by twelve sensors placed on a 30 diameter circle surrounding the projection of the fovea. The resulting signal is close to the "ideal" sine wave that would have been recorded from a propeller-type birefringence pattern from a human fovea. The transducer can be used in the detection of fixation for medical and other purposes. It does not require calibration, strict restrictions on head position, or head-mounted appliances.

Attention attraction in an ophthalmic diagnostic device using sound-modulated fixation targets.

This study relates to eye fixation systems with combined optical and audio systems. Many devices for eye diagnostics and some devices for eye therapeutics require the patient to fixate on a small target for a certain period of time, during which the eyes do not move and data from substructures of one or both eyes are acquired and analyzed. With young pediatric patients, a monotonously blinking target is not sufficient to retain attention steadily. We developed a method for modulating the intensity of a point fixation target using sounds appropriate to the child's age and preference. The method was realized as a subsystem of a Pediatric Vision Screener which employs retinal birefringence scanning for detection of central fixation. Twenty-one children, age 2-18, were studied. Modulation of the fixation target using sounds ensured the eye fixated on the target, and with appropriate choice of sounds, performed significantly better than a monotonously blinking target accompanied by a plain beep. The method was particularly effective with children of ages up to 10, after which its benefit disappeared. Typical applications of target modulation would be as supplemental subsystems in pediatric ophthalmic diagnostic devices, such as scanning laser ophthalmoscopes, optical coherence tomography units, retinal birefringence scanners, fundus cameras, and perimeters.

New pediatric vision screener, part II: electronics, software, signal processing and validation.

BACKGROUND: We have developed an improved pediatric vision screener (PVS) that can reliably detect central fixation, eye alignment and focus. The instrument identifies risk factors for amblyopia, namely eye misalignment and defocus. METHODS: The device uses the birefringence of the human fovea (the most sensitive part of the retina). The optics have been reported in more detail previously. The present article focuses on the electronics and the analysis algorithms used. The objective of this study was to optimize the analog design, data acquisition, noise suppression techniques, the classification algorithms and the decision making thresholds, as well as to validate the performance of the research instrument on an initial group of young test subjects-18 patients with known vision abnormalities (eight male and 10 female), ages 4-25 (only one above 18) and 19 controls with proven lack of vision issues. Four statistical methods were used to derive decision making thresholds that would best separate patients with abnormalities from controls. Sensitivity and specificity were calculated for each method, and the most suitable one was selected. RESULTS: Both the central fixation and the focus detection criteria worked robustly and allowed reliable separation between normal test subjects and symptomatic subjects. The sensitivity of the instrument was 100 % for both central fixation and focus detection. The specificity was 100 % for central fixation and 89.5 % for focus detection. The overall sensitivity was 100 % and the overall specificity was 94.7 %. CONCLUSIONS: Despite the relatively small initial sample size, we believe that the PVS instrument design, the analysis methods employed, and the device as a whole, will prove valuable for mass screening of children.

Detection of central fixation using short-time autoregressive spectral estimation during retinal birefringence scanning.

The manuscript reports on the implementation of autoregressive spectral estimation aimed at improving the accuracy of detecting short-lasting events in signals acquired by a retinal birefringence scanning device that was reported earlier. A signal consisting of two frequency components is generated, where each frequency is a multiple of the scanning frequency. One frequency is produced during central fixation, while another one prevails during off-central fixation. These components may be of a very short duration, presenting a challenge for the FFT to identify them with sufficient time- and frequency resolution. Autoregressive spectral estimation using the Burg algorithm provided a satisfactory solution, capable of reliably differentiating between the two frequency components (96 and 192 Hz) on signal segments of duration as short as 5 ms. The device and the signal analysis methods were developed originally with the purpose of checking for eye alignment and strabismus - a major risk factor for amblyopia. The method enables the technology to work with less-cooperative patients, such as young children. Other medical and non-medical applications are possible.

Optimal timing of retinal scanning during dark adaptation, in the presence of fixation on a target: the role of pupil size dynamics.

While validating our newly developed vision screener based on a double-pass retinal scanning system, we noticed that in all patients the signals from the retina were significantly higher when measurements were performed within a certain time interval referenced to the initial moment when the lights were dimmed and the test subject was asked to fixate on a target. This appeared to be most likely attributable to pupil size dynamics and triggered the present study, whose aim was to assess the pupillary "lights-off" response while fixating on a target in the presence of an accommodative effort. We found that pupil size increases in the first 60 to 70 s after turning off the room lights, and then it decreases toward the baseline in an exponential decay. Our results suggest that there is an optimal time window during which pupil size is expected to be maximal, that is during the second minute after dimming the room lights. During this time, window retinal diagnostic instruments based on double-pass measurement technology should deliver an optimal signal-to-noise ratio. We also propose a mathematical model that can be used to approximate the behavior of the normalized pupil size.

New pediatric vision screener employing polarization-modulated, retinal-birefringence-scanning-based strabismus detection and bull's eye focus detection with an improved target system: opto-mechanical design and operation.

Amblyopia ("lazy eye") is a major public health problem, caused by misalignment of the eyes (strabismus) or defocus. If detected early in childhood, there is an excellent response to therapy, yet most children are detected too late to be treated effectively. Commercially available vision screening devices that test for amblyopia's primary causes can detect strabismus only indirectly and inaccurately via assessment of the positions of external light reflections from the cornea, but they cannot detect the anatomical feature of the eyes where fixation actually occurs (the fovea). Our laboratory has been developing technology to detect true foveal fixation, by exploiting the birefringence of the uniquely arranged Henle fibers delineating the fovea using retinal birefringence scanning (RBS), and we recently described a polarization-modulated approach to RBS that enables entirely direct and reliable detection of true foveal fixation, with greatly enhanced signal-to-noise ratio and essentially independent of corneal birefringence (a confounding variable with all polarization-sensitive ophthalmic technology). Here, we describe the design and operation of a new pediatric vision screener that employs polarization-modulated, RBS-based strabismus detection and bull's eye focus detection with an improved target system, and demonstrate the feasibility of this new approach.

Modern technologies for retinal scanning and imaging: an introduction for the biomedical engineer.

This review article is meant to help biomedical engineers and nonphysical scientists better understand the principles of, and the main trends in modern scanning and imaging modalities used in ophthalmology. It is intended to ease the communication between physicists, medical doctors and engineers, and hopefully encourage "classical" biomedical engineers to generate new ideas and to initiate projects in an area which has traditionally been dominated by optical physics. Most of the methods involved are applicable to other areas of biomedical optics and optoelectronics, such as microscopic imaging, spectroscopy, spectral imaging, opto-acoustic tomography, fluorescence imaging etc., all of which are with potential biomedical application. Although all described methods are novel and important, the emphasis of this review has been placed on three technologies introduced in the 1990's and still undergoing vigorous development: Confocal Scanning Laser Ophthalmoscopy, Optical Coherence Tomography, and polarization-sensitive retinal scanning.

Improved eye-fixation detection using polarization-modulated retinal birefringence scanning, immune to corneal birefringence.

We present an improved method for remote eye-fixation detection, using a polarization-modulated approach to retinal birefringence scanning (RBS), without the need for individual calibration or separate background measurements and essentially independent of corneal birefringence. Polarization-modulated RBS detects polarization changes generated in modulated polarized light passing through a unique pattern of nerve fibers identifying and defining the retinal region where fixation occurs (the fovea). A proof-of-concept demonstration in human eyes suggests that polarization-modulated RBS has the potential to reliably detect true foveal fixation on a specified point with an accuracy of at least ± 0.75°, and that it can be applied to the general population, including individuals with sub-optimal eyes and young children, where early diagnosis of visual problems can be critical. As could be employed in an eye-controlled display or in other devices, polarization-modulated RBS also enables and paves the way for new and reliable eye-fixation-evoked human-machine interfaces.

Use of retinal nerve fiber layer birefringence as an addition to absorption in retinal scanning for biometric purposes.

We built a device sensitive to the birefringence of the retinal nerve fiber layer for biometric purposes. A circle of 20 degrees diameter on the retina was scanned around the optic disk with a spot of light from a 785 nm laser diode. The nonbirefringent blood vessels indenting or displacing the retinal nerve fiber layer were seen as "blips" in the measured birefringence-derived signal. For comparison, the reflection-absorption signature of the blood vessel pattern in the scanned circle was also measured. The birefringence-derived signal proved to add useful information to the reflectance-absorption signature for retinal biometric scanning.

Directional eye fixation sensor using birefringence-based foveal detection.

We recently developed and reported an eye fixation monitor that detects the fovea by its radial orientation of birefringent nerve fibers. The instrument used a four-quadrant photodetector and a normalized difference function to check for a best match between the detector quadrants and the arms of the bow-tie pattern of polarization states surrounding the fovea. This function had a maximum during central fixation but could not tell where the subject was looking relative to the center. We propose a linear transformation to obtain horizontal and vertical eye position coordinates from the four photodetector signals, followed by correction based on a priori calibration information. The method was verified on both a computer model and on human eyes. The major advantage of this new eye-tracking method is that it uses true information coming from the fovea, rather than reflections from other structures, to identify the direction of foveal gaze.

Rapid, objective detection of cataract-induced blur using a bull's eye photodetector.

PURPOSE: To determine whether optical aberrations caused by cataract can be detected and quantified objectively using a newly described focus detection system (FDS). SETTING: The Wilmer Opthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. METHODS: The FDS uses a bull's eye photodetector to measure the double-pass blur produced from a point source of light. To determine the range and level of focus, signals are measured with a series of trial lenses in the light path selected to span the point of best focus to generate focus curves. The best corrected visual acuity (BCVA), refractive error, lens photograph grades, and FDS signals were obtained in 18 patients scheduled to have cataract surgery. The tests were repeated 6 weeks after surgery. RESULTS: The mean FDS outcome measures improved after cataract surgery, with increased peak height (P=.001) and decreased peak width (P=.001). Improvement in signal strength (integral of signal within +/-1.5 diopters of the point of best focus) strongly correlated with improvement in peak height (R(2)=.88, P<.0001) and photographic cataract grade (R(2)=.72, P<.0001). The mean BCVA improved from 20/50 to 20/26 (P<.0001). The improvement in BCVA correlated more closely with FDS signal strength (R(2)=.44, P=.001) than with cataract grade (R(2)=.25, P=.06). CONCLUSIONS: Improvement in FDS outcome measures correlated with cataract severity and improvement in visual acuity. This objective approach may be useful in long-term studies of cataract progression.

Pediatric Vision Screener 1: instrument design and operation.

We develop the Pediatric Vision Screener (PVS) to automatically detect ocular misalignment (strabismus) and defocus in human subjects. The PVS utilizes binocular retinal birefringence scanning to determine when both eyes are aligned, with a theoretical accuracy of <1 deg. The device employs an autoconjugate, bull's-eye detector-based system to detect focus. The focus and alignment pathways are separated by both wavelength and data acquisition timing. Binocular focus and alignment are detected in rapid alternating sequence, measuring both parameters in both eyes in <0.5 sec. In this work, the theory and design of the PVS are described in detail. With objective, automated measurement of both alignment and focus, the PVS represents a new approach to screening children for treatable eye disease such as amblyopia.

Pediatric Vision Screener 2: pilot study in adults.

Amblyopia is a form of visual impairment caused by ocular misalignment (strabismus) or defocus in an otherwise healthy eye. If detected early, the condition can be fully treated, yet over half of all children with amblyopia under age 5 escape detection. We developed a Pediatric Vision Screener (PVS) to detect amblyopia risk factors. This instrument produces a binocularity score to indicate alignment and a focus score to indicate focus. The purpose of this study is to assess the performance of the PVS by testing adults who were fully cooperative for testing. The study group includes 40 subjects (20 controls, 20 patients) aged 22 to 79 years. 12 patients had constant strabismus (8 to 50Delta), and eight had variable strabismus (12 to 55Delta). All controls had binocularity scores >50%. Binocularity was <50% in 11/12 patients. The patient with binocularity >50% had a well-controlled intermittent exotropia and was not at risk for amblyopia. Focus scores were highly sensitive for good focus but not specific. The PVS shows high sensitivity and specificity for detection of strabismus in adults. Future studies will determine whether this performance can be achieved in preschool children, who are at greatest risk for vision loss.

Automated detection of ocular focus.

We characterize objectively the state of focus of the human eye, utilizing a bull's eye photodetector to detect the double-pass blur produced from a point source of light. A point fixation source of light illuminates the eye. Fundus-reflected light is focused by the optical system of the eye onto a bull's eye photodetector [consisting of an annulus (A) and a center (C) of approximately equal active area]. To generate focus curves, C/A is measured with a range of trial lenses in the light path. Three human eyes and a model eye are studied. In the model eye, the focus curve showed a sharp peak with a full width at half maximum (FWHM) of +/-0.25 D. In human eyes, the ratio C/A was >4 at best focus in all cases, with a FWHM of +/-1 D. The optical apparatus detects ocular focus (as opposed to refractive error) in real time. A device that can assess focus rapidly and objectively will make it possible to perform low-cost, mass screening for focusing problems such as may exist in children at risk for amblyopia.