Methods, systems, and devices for visual testing

Abstract

To provide methods, systems and devices for improving the assessment of the visual function and overcoming limitations of current methods for identifying the visual function that may potentially be reached by a given eye.SOLUTION: Multiple eye tests includes visual stimuli and optical measurement components, and methods of combining the results to identify and quantify sources of decreased vision resulting from optical sources, such as a lens and a cornea as distinguished from retinal sources. By identifying potentially correctable optical sources of decreased vision, and overcoming physiological limitations such as size of the eye's pupil, visual benefits of treatment such as cataract or corneal surgery are distinguished from retinal pathology that requires medical intervention. The devices and methods provide metrics that include an expected value of the visual function and sources of variability including both optical and neural components, to guide treatment and improve clinical trials.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] Description of Research and Development with Federal Government Funds This invention was made with government support under grant EY030829 awarded by the National Institutes of Health. The government has certain rights in this invention.

[0002] Related Applications This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Patent Application No. 17 / 554,703, filed December 17, 2021, entitled "Methods, Systems, and Devices for Visual Inspection," the entire disclosure of which is hereby incorporated by reference.

Background Art

[0003] Visual acuity and other visual functions serve as guidelines for managing patients with retinal diseases and conditions. Such visual function tests also serve as endpoints in clinical trials to evaluate treatment options. Printed or electronic test charts used to measure visual acuity or other visual functions are commonly used because they are standardized, easy to use, and widely available, but they are inaccurate for the purpose of assessing the condition of the retina. Such test charts cannot minimize or quantify factors that degrade the performance of the eye due to optical factors such as stray light, insufficient transmittance, the tear layer, the cornea, or a lack of sharp focus due to problems with the lens.

[0004] Additional optical factors include, but are not limited to, the lack of proper refraction, particularly when refractive error correction is not performed simultaneously with measurements using visual function charts, or when the retinal plane at the target position is altered by subretinal fluid, etc. Furthermore, methods using visual acuity charts cannot control pupil size. Pupil size varies greatly from person to person, and pupils often shrink with age, which can significantly reduce the amount of light transmitted through the retina. When one or more causes of optical degradation are present, the common clinical practice of creating a pinhole to minimize the angle at which light can enter the eyeball and the cross-section of the pupil through which light can pass can introduce even greater variability in light transmission. Methods using charts do not control or specify the fixation position of the eyeball that aligns the visual stimulus to the retina, leading to a lack of information about retinal regions useful for visual function measurements. Furthermore, charts do not specify fixation stability, which affects vision when fixation stability is lacking.

[0005] Numerous optical devices provide one or more design features to visual displays, allowing these display features to control or identify information that influences the assessment of ocular function. For visual acuity, which is closely related to retinal function, all of these display factors, including high-resolution displays and models combining information, are relevant to determining retinal function. Factors such as accurate stimuli and the number of letters affect the performance of visual tests, including visual acuity tests. While potentially important for estimating reading ability, such tests may compromise accuracy when assessing retinal condition. Models used to improve the accuracy and testing efficiency of visual acuity and other visual functions include procedural details and stimulus parameters. However, these models do not adequately minimize or identify the influence of central tendencies and variability of optical and performance factors on the visual function measurements within the model. The measurement and modeling of the non-retinal factors described above are necessary to identify retinal visual function and the potential vision that can be achieved through treatment.

[0006] The present invention aims to improve and resolve some of these known defects in the related art. That's the intention. [Overview of the project]

[0007] This invention relates to methods, systems, and devices designed for diagnostic use by ophthalmic healthcare professionals and researchers in clinical trials to more accurately identify the visual function of the eyeball and the potential for improvement through treatment. The methods, systems, and devices achieve ease of operation, patient comfort, and efficiency. They are suitable for providing a wide range of information necessary to identify the cause of vision loss, which influences treatment decisions. The system has several subsystems, which, when combined, provide improved accuracy and can be manufactured at a significantly lower cost than systems that perform only some of the subsystem functions, or can provide better accuracy and efficiency. The devices and systems can easily interface with modern computer technology to augment databases used for decision-making or transmit information to external databases for decision-making regarding treatment.

[0008] The technology of this disclosure provides devices and methods far more advanced than typical wall-mounted charts or computer screens, particularly highlighting problems associated with presbyopia. Errors and variability are direct consequences of these artifacts and cannot be overcome by software or algorithms alone, many of which have been proposed to address specific stimuli or visual acuity charts, such as specific stimuli or targets, algorithms for presenting stimuli, or test factors such as patient fatigue, criteria used by the patient, or cognitive impairment. See, for example, Lesmes U.S. Patent No. 10758120. The technological innovations of this disclosure improve many of these problems by combining one or more of the following features:

[0009] The present invention provides 1) evaluation of fixation point position using video-rate and near-infrared retinal imaging invisible to the patient. The portion of the retina used for fixation and for performing visual function tests is positioned. Because the human eyeball moves frequently, the position of the visual stimulus relative to the state of the retina cannot be determined without retinal imaging at or near video rate. Wall-mounted charts and computer screens cannot demonstrate this relevance. Therefore, it is not possible to know whether the portion of the retina considered for treatment is actually in the position on which the measured performance is based. Video-rate retinal imaging determines this position. Furthermore, without retinal imaging that is relatively fast relative to eye movements, it is not possible to determine whether there is oscillation in the eyeball, whether the visual target is blurred across the retina, or whether the eyeball is in a position long enough to allow detection or recognition of the visual target. As used herein, video rate includes an image capture or display rate of at least 10 frames per second.

[0010] The widespread use of near-infrared light as an illumination source to provide retinal images that visualize retinal landmarks and structures, instead of other wavelengths or color images, is discussed extensively in Elsner, AE et al., Infrared Imaging of Sub-retinal Structures in the Human Ocular Fundus, Vision Res, Vol. 36, No. 1 (1996), pp. 191-205 (Elsner et al., 1996). Several implementations have been demonstrated by the inventor, AE Elsner. For example, see Elsner, AE, Burns, SA, Hughes, GW, and Webb, RH (1992). Reflectometry with a scanning laser ophthalmoscope. Applied Optics, 31(19), 3697-3710 (Elsner et al., 1992) and Elsner, AE et al., Multiply scattered light tomography: Vertical cavity surface emitting laser array used for imaging subretinal structure, Lasers and Light in Ophthalmology, 1998 (Elsner et al., 1998a).

[0011] Each embodiment has its own unique characteristics, but the high-quality images of the retina obtained by numerous methods are suitable for combining with projections of visual stimuli onto the retina, while providing information about the state of the retina in eye diseases, for example, by scanning with light points and synchronously detecting light returning from the retina one point at a time: Hartnett, ME and Elsner, AE, Characteristics of Exudative Age-related Macular Degeneration Determined In Vivo with Confocal and Indirect Infrared Imaging, Ophthalmology, Vol. 103, No. 1 (January 1996), pp. 58-71 (Hartnett et al., 1996a); and Hartnett, ME et al., Deep Retinal Vascular Anomalous Complexes in Advanced Age-related Macular Degeneration, Ophthalmology, Vol. 103, No. 12 (December 1996), pp. 2042-2053 (Hartnett et al., 1996b). The positions of fixation and visual stimuli on the patient's retina have been well visualized by the inventor A.E. Elsner and collaborators: Remky, A., Elsner, A.E., Morandi, A.J., Beausencourt, E., and Trempe, CL (2001).Blue-on-yellow perimetry with a scanning laser ophthalmoscope: small alterations in the central macula with aging vision,18(7)、1425~1436;(Remkyらによる、2001);.Remky, A. and Elsner, AE(2005). ophthalmology,89(4) 464~469(Remky, 2005); I, C., Suzuki, H., Nehemiah, MB, Soriano, DS, and Kara-Jose, N. (2007).Avaliacao. of macular perimetry in patients with age-related macular degeneration due to laser tracking ophthalmoscope-Evaluation of macular perimetry in patients with age-related macular degeneration using the scanning laser ophthalmoscope.Brazilian archives of ophthalmology,70(5),844~850(Moraesらによる、2007).

[0012] Similar methods have been used by the inventors to image the retina using near-infrared illumination consisting of a scanned light strip and a detection synchronized with either a one-dimensional or two-dimensional array: see, for example, U.S. Patent No. 7,331,669, U.S. Patent No. 7,831,106, U.S. Patent No. 8,237,835, and U.S. Patent No. 8,488,895. The near-infrared image of the retina is combined with a visual display so that the trajectory of fixation points and the position of stimuli on the retina are clearly recorded using near-infrared or long-wavelength visible illumination as shown by Elsner, AE, Petrig, BL, Papay, JA, Kollbaum, EJ, Clark, CA, and Muller, MS (2013), as described herein. Fixation stability and scotoma mapping for patients with low vision. Optometry and vision science: official publication of the American Academy of Optometry, 90(2), 164-173 (Elsner et al., 2013) and Elsner, AE, Papay, JA, Johnston, KD, Sawides, L., de Castro, A., King, BJ, Jones, DW, Clark, CA, Gast, TJ, and Burns, SA (Elsner et al., 2020). Cones in aging and harsh environments: the neural economy hypothesis. Ophthalmic & physical optics: The Journal of the British College of Ophthalmic Opticians (Optometrists), 40(2), 88-116 (Elsner et al., 2020).

[0013] The present invention provides (2) an evaluation of gaze stability using the same video rate near-infrared retinal imaging. Patient eye movements are analyzed by aligning retinal images acquired over time.

[0014] The present invention (3) identifies optical errors in a patient's eye, including, but not limited to, spherical and cylindrical, those resulting from pathological or aging conditions observed in the cornea, lens, or pupil, collected by wavefront sensor measurements of light returning from the retina. These errors arise from wavefront aberrations that cause complex blurring on the retina, making it difficult to determine whether decreased visual acuity is due to retinal disease or anterior segment problems such as cataracts or poor tear film. It has long been known that aging increases these optical errors that blur visual stimuli on a patient's retina, and blurring cannot be easily improved by simply adding spherical or cylindrical correction, as seen in eyeglasses. See, for example, how age-related changes in monochromatic wave aberration of the human eye can be measured, as reported by McLellan, JS, Marcos, S., and Burns, SA (2001); Investigative Ophthalmology & Visual Science, 42(6), 1390-1395. Accordingly, the present disclosure provides one or more embodiments including a method and / or apparatus that highlights improvements in the characterization of the factors underlying the visual performance or function of aging eyes, which reduce costs and improve the accuracy of analyzing the condition of the eye.

[0015] The present invention (4) provides objective correction using an adaptive optical system during the measurement of the primary optical errors of a patient's eyeball, not limited to spherical and cylindrical, using the wavefront measurements described above in item (3). The present invention also provides an estimate of the accuracy of the measurements leading to correction and a predicted success of correction. This makes it possible to perform visual function tests using a precisely focused directional light beam on the retina, thereby providing better and more complete results than can be achieved with mere standard spherical and cylindrical correction or with conventional refraction, which often produces significant errors when the retina is elevated as a result of exudative eye disease. This feature, in essence, provides even greater accuracy when used in combination with other features not found in automatic refractors that include only spherical and cylindrical elements.

[0016] Optical correction necessary to provide correction of higher-order aberrations, and therefore necessary to improve the measurement of visual function that depends on high contrast at high spatial resolution, was impossible before the use of wavefront-corrected imaging of the fundus by the authors and colleagues Burns, SA, Marcos, S., Elsner, AE, and Bara, S. (2002). Contrast improvement of confocal retinal imaging by use of phase-correcting plates. Optics Letters, 27(6), 400-402. Previous instruments provided fundus images and visual stimuli, but lacked sufficient spatial resolution to test visual acuity, as first demonstrated by Timberlake and colleagues Timberlake, GT, Mainster, MA, Peli, E., Augliere, RA, Essock, EA, and Arend, LE (1986). Reading with a macular scotoma.I.Retinal location of scotoma and fixation area.Investigative ophthalmology&visual science,27(7), 1137~1147.

[0017] In the above-mentioned and cited known conventional methods for refractive correction beyond the spherical and cylindrical surfaces, wavefront measurement devices are used in combination with retinal images. In embodiments to reduce the cost and complexity of components, it is possible to quantify the optical quality of the eyeball using information within the image. This has been done to examine the refractive errors of spherical components. Peripheral Refraction Across The Posterior Pole Using Structured Illumination.ARVO Annual Meeting,Investigative Ophthalmology&Visual Science 52(14),2717~2717,2011(Clark et al., 2011);Elsner AE,Muller MS,Petrig BL,Papay JA,Christopher CA,Jovan A,Haggerty BP.Toward Low Cost Imaging:A Laser Scanning Digital Camera.Bio-Optics:Design and Application(BODA)2011 Paper: BWA1 (by Elsner et al., 2011).

[0018] Furthermore, information within the fundus image provides autofocus for the retinal camera. This technique is known as sensorless adaptive optics (AO) as described by Burns, SA, Elsner, AE, Sapoznik, KA, Warner, RL, and Gast, TJ (2019). Adaptive optics imaging of the human retina Progress in retinal and eye research, 68, 1~30 (Burns et al., 2019). In some cases, the retinal image functions as a sensor. By injecting spatial patterns such as black and white stripes into the illumination, the contrast of the fundus image described in Clark's reference above is improved. Thus, in practice, a sensor exists, namely the retinal image and the calculation. Projection of patterns onto the retina has been achieved with both point scanning and line scanning, but the use of wide-field images and the calculation of wavefront errors based on specific parts of the retinal image with a known spatial relationship to the fixation point have not been pursued. The area of ​​the retina corrected by the adaptive optics may or may not be located at the fovea or fixation point; that is, the visual stimulus is viewed eccentrically, or the peripheral visual field is examined. The quality of this calculation is a measure of the optical quality of the eye, and the results can be used to assess and evaluate the variability of potential visual performance. This optical quality is quantified by repeated measurements, even with eye movement, based on the calculation of the fundus image corrected by the adaptive optics. The feedback loop then consists of the fundus image, the calculation from the image, and the adaptive optics. See, for example, Clark, 2010; Clark, 2011; Elsner, 2011.

[0019] It is well known that considering factors of visual stimuli, including retinal eccentricity (distance from the fovea) and contrast, along with specific algorithms, can improve the sensitivity of visual function tests (Hahn, GA; Messias, A.; Mackeben, M.; Dietz, K.; Horwath, K.; Hyvarinen, L.; Leinonen, M.; and Trauzettel-Klosinski, S. (2009). Parafoveal letter recognition at reduced contrast in normal aging and in patients with risk factors for AMD. Graefe's archive for clinical and experimental ophthalmology - Albrecht von Graefes Archiv fur klinische und experimentelle). Ophthalmologie, 247(1), 43-51. The distance of a visual stimulus from the fovea is quantified by retinal imaging. Measurement of the contrast of visual stimuli projected onto the retina through the optical system of the eyeball is improved by the use of wavefront measurement. To reduce cost and complexity, information on the contrast of visual stimuli on the retina can also be provided using calculations from the retinal image, with or without structured illumination. Another way to reduce cost and complexity is to use a visual display as illumination for the wavefront sensor. Currently, due to the limited sensitivity of current sensors, simultaneous measurement of the contrast of visual stimuli on the retina during visual function measurement is difficult. Generally, NIR illumination is preferred because visible wavelength illumination must be very bright and interfere with visual function tasks. However, in one or more of the disclosed embodiments, the visual display is used as an illumination source for estimating wavefront errors by alternating between a visual stimulus having wavelengths in the visible range and a measurement of contrast by either a wavefront sensor or a retinal imaging method. In one or more embodiments, light with wavelengths shorter than near-infrared (NIR) is used. In another embodiment, time modulation of illumination for the wavefront sensor or retinal image may also be used to provide a frequency-based detection scheme for improving the signal-to-noise ratio.In other embodiments, more complex frequency-based homodyne and heterodyne detection schemes are used to improve the signal-to-noise ratio.

[0020] Aside from recent augmented reality (AR) and virtual reality (VR) devices, previous products that provided refractive correction beyond spherical and cylindrical surfaces have so far found limited markets because the wavefront information and correction cannot be applied to ordinary spectacle lenses or contact lenses that do not precisely position the pupil relative to the corrective device. Expensive devices such as headsets or experimental devices for AR or VR can have positioning mechanisms, and intraocular lenses can utilize this (higher-order refractive) information through their positioning relative to the pupil.

[0021] The present invention (5) projects a visual target onto the retina through a fixed-size pupil of the device and reduces large variations due to individual differences in the patient's natural pupil size when compared to an ideal pupil size or based on the amount of light reaching the retina through the pupil.

[0022] Differences in pupil size not only increase or decrease the amount of light reaching the retina, but also alter optical throughput due to differences in numerical aperture and depth of focus at the entrance pupil of the eyeball. This method of projecting visual targets is a known technique and is used in a wide variety of applications, and is employed in many versions of devices that provide fundus imaging, giving both retinal images and projections of visual stimuli. This includes devices that incorporate both visual stimuli as part of the illumination that scans the point. For additional information, please refer to the following references: Timberlake, GT, Mainster, MA, Peli, E., Augliere, RA, Essock, EA, and Arend, LE (1986). Reading with a macular scotoma. I. Retinal location of scotoma and fixation area. Investigative ophthalmology & visual science, 27(7), 1137-1147, or line scanning by Elsner et al. (2020), and point scanning including correction of higher-order optical aberrations by Rossi, EA, Weiser, P, Tarrant, J., and Roorda, A (2007). Visual performance in emmetropia and low myopia after correction of high-order aberrations. Journal of vision, 7(8), 14 (Rossi et al., 2007) mentions that when scanning points to generate a retinal image, or scanning lines to generate a retinal image (Elsner et al., 2013), the retinal image and visual stimulus are provided by separate illumination channels, as described by Remky et al., 2001; Remky et al., 2005; and Moraes et al., 2007. Several embodiments are described in U.S. Patent No. 7,331,669, U.S. Patent No. 7,831,106, U.S. Patent No. 8,237,835, and U.S. Patent No. 8,488,895.

[0023] The present invention 6) provides confocal and multiple scatter light analysis of retinal images, or provides imaging modes that adjust the time or positional difference (temporal or spatial detection offset) between illumination and detection. Different imaging modes, as described in U.S. Patents 7,331,669, 7,831,106, 8,237,835, and 8,488,895, clarify the state of the retina at that location and detail the precise lesion at the fixation point used by the patient in a visual examination by using confocal or multiple scatter light imaging and a combination of information from different imaging modes. Further examples of detection offsets include, but are not limited to, the ratio at each location in the image of the intensity difference in each image to the sum at each location, the ratio at each location in the image of the intensity of the confocal image intensity to the image with a larger offset, and similar calculations that aggregate an area wider than a particular location or pixel. Infrared imaging using scanning laser ophthalmoscopy (SLO), multiple scatter tomography (CTO), laser scanning digital cameras, and digital optical ophthalmoscopy has been used to implement reflectivity measurement techniques for rapid and non-invasive visualization of the eye. Initially, infrared and near-infrared imaging of the subretinal structures of the fundus, performed using scanning laser devices, was able to reveal subretinal deposits, optic nerve heads, retinal blood vessels, choroidal blood vessels, fluid accumulation, hyperpigmentation, atrophy, and Bruch's membrane damage. Infrared light is absorbed less than visible light and can scatter over longer distances. In flood illumination, these features are not observed with the same clarity and are present in fewer numbers. The relatively low absorption has the advantage of allowing the use of minimal light as an illumination source. However, reflected and scattered light must be separated in some way so that the user can utilize the light used to highlight the features of interest.

[0024] Methods for detecting and localizing such features include, as exemplified, prior art by the inventors and their colleagues: Elsner et al., 1996; 1998a; Elsner, AE et al., Foveal Cone Photopigment Distribution: Small Alterations Associated with Macular Pigment Distribution, Investigative Ophthalmology & Visual Science, Vol. 39, No. 12 (November 1998), pp. 2394-2404; Hartnett et al., 1996a; Hartnett et al., 1996b; Remky et al., 2005; and Elsner et al., 2020. Specifically, when the acquired retinal image consists only of the macula centered on the fovea, the only features present in a normal eyeball with near-infrared illumination are retinal and choroidal vessels, as well as potential surface reflections from the fovea, etc. In monochromatic images, any difference in image intensity from these features, beyond the noise inherent in any given electronic signal, is interpreted as a lesion. If the optic nerve head is also in the image, either due to a sufficiently wide field of view or the positioning of the eyeball relative to an instrument for incorporating this feature, then changes in retinal intensity also define the location and state of such structures. Hartnett et al., 1996a; Elsner et al., 1996; and Miura, M et al., Grading of Infrared Confocal Scanning Laser Tomography and Video Displays of Digitized Color Slides in Exudative Age-Related Macular Degeneration, Retina, Vol. 22, No. 3 (2002), pp. 300-308, show that such monochrome images using infrared illumination are superior to methods using color photographs for detecting certain features.

[0025] The present invention further provides 7) a novel system for measuring potential vision, including combinations of all the above components 1-6, using proprietary statistical analysis. This disclosure provides metrics using measures of central tendency, such as mean, and in addition, metrics of variability, such as variance, to report the significance of confounding reasons for visual impairment. For example, reporting from wavefront error shows how visual measurements are limited in cataracts. Proprietary statistical analysis combines information from the various sources described above to draw boundaries on predicted performance. For example, to determine the potential vision that a particular eye can achieve with retinal treatment, there are boundaries such as central tendency (predicted value) and confidence limits derived from variability, including optical error, fixation data, and other data. Using aberrations that have been measured and determined to be correctable, upper and lower limits of potential vision can be realized with measurements such as the logarithm of minimum visual angle (LogMAR), which is widely used in characterizing visual acuity. Sampling methods include, but are not limited to, a paradigm in which the target is tumbling E and the four possible directions E may point to, but only one patient response is allowed (a four-choice forced choice). Statistical analysis includes determining whether optical, neurological, and other factors are independent or must be modeled as interacting with each other.

[0026] The important gist of the model includes a set of data for determining whether variables are independent and whether the overall variance is the sum of the variances of individual factors. Conversely, the model may require a function that exceeds the simple addition of the variances of two or more variables that must be used to calculate the predicted visual function performance after optical factors are corrected. Further, each variable may have a function more complex than a Gaussian distribution, and the variance may be distributed in such a way that it is not symmetric about the mean value and does not scale linearly with respect to the mean value. The combined variance is used to calculate the upper confidence limit and the lower confidence limit. These confidence limits, i.e., the boundaries used to interpret the visual function test scores, widen or narrow depending on the function that combines the variances of the component factors. The upper limit corresponds to the value that the visual function measurement must exceed in order for retinal treatment to be considered successful or to be counted as an improvement in long-term measurements. The lower limit is the value that the visual function must exceed or corresponds to the value that is considered not to have deteriorated in follow-up observations. These values may be related to current metrics such as lines of visual gain or loss that lack an important assessment of optical effects, fixation stability, or other factors.

[0027] The above aspects of the present invention and the manner of obtaining them will become more apparent by referring to the following description of embodiments of the present invention in conjunction with the accompanying drawings, and the present invention itself will be better understood.

Brief Description of the Drawings

[0028] [Figure 1] Figure 1 is a schematic diagram of an eyeball showing a selected tissue having a pupil onto which light from a visual display is projected. [Figure 2] Figure 2 is a schematic diagram of an optical imaging system used to measure visual function, including a wavefront measurement subsystem for correcting the aberrations of the eyeball. [Figure 3] Figure 3 is a schematic diagram of an optical imaging system used to measure visual function that does not include a wavefront measurement subsystem. [Figure 4]Figure 4 is a schematic diagram of an optical imaging system used to measure visual function, including a wavefront measurement subsystem that uses a visible wavelength display as an illumination source. [Figure 5] Figure 5 is a schematic diagram of an exemplary embodiment of a device for determining visual function when using the Hartmann-Shack method for optical aberration measurement. [Figure 6A] Figure 6A shows sample graphs of low-order and higher-order aberrations (LOA) from near-infrared (NIR) wavelength measurements, illustrating the effects of aging and refractive error. [Figure 6B] Figure 6B shows sample graphs of low-order and higher-order aberrations (LOA) from near-infrared (NIR) wavelength measurements, illustrating the effects of aging degradation and refractive error. [Figure 6C] Figure 6C shows sample graphs of low-order and higher-order aberrations (LOA) from near-infrared (NIR) wavelength measurements, illustrating the effects of aging and refractive error. [Figure 6D] Figure 6D shows sample graphs of low-order and higher-order aberrations (LOA) from near-infrared (NIR) wavelength measurements, illustrating the effects of aging and refractive error. [Figure 7A] Figure 7A shows one method for recording wavefront aberration and illustrates the difference between young and elderly patients. [Figure 7B] Figure 7B shows one method for recording wavefront aberration and illustrates the difference between young and elderly patients. [Figure 8A] Figure 8A shows another method for recording wavefront aberration and illustrates the difference between young and elderly patients in the plot of wavefront aberration in the pupillary plane. [Figure 8B] Figure 8B shows another method for recording wavefront aberration and illustrates the difference between young and elderly patients in the plot of wavefront aberration in the pupillary plane. [Figure 9A] Figure 9A shows the predicted degradation of contrast in the letter E due to wavefront aberration, comparing the eyeballs of a young person with hyperopia and an elderly person with myopia. [Figure 9B]Figure 9B shows the predicted degradation of contrast in the letter E due to wavefront aberration, comparing the eyeballs of a young person with hyperopia and an elderly person with myopia. [Modes for carrying out the invention]

[0029] The embodiments of the present invention described below are not intended to be exhaustive or to limit the invention to the exact forms disclosed in the following detailed description. Rather, the embodiments are selected and described so that those skilled in the art can recognize and understand the principles and practices of the present invention.

[0030] Figure 1 shows a schematic diagram of an eyeball 10 showing the pupil 16 from which light from a light source providing a visual stimulus, such as a visual display, is projected, as well as the projection of the visual stimulus and selected tissues including the retinal surface 12 as a focal target surface for imaging the retina and subretinal structures, the cornea 26, the lens 24, and other anterior segment structures. As used herein, “visual display” is used to describe a device that transmits a visible or invisible light image directed to and received by the patient’s eyeball. Once received by the eyeball, the patient undertakes the task of determining one or more aspects of visual function, including but not limited to visual acuity.

[0031] Depending on the condition of various tissues in the eyeball, strong unwanted reflections and the location of potential unwanted light scattering, as well as aberrations and lack of transparency due to pathological conditions or aging, adversely affect the retinal image that appears in the anterior segment 22 of the eyeball 10. Unwanted reflections adversely affect the retinal image, the location of potential unwanted light scattering aberrations, and lack of transparency due to pathological conditions or aging. The anterior segment 22 is generally located in or near the pupil 16, lens 24, and cornea 26. Retinal diseases, including but not limited to diabetic macular edema and exudative age-related macular degeneration, can cause one or more parts of the retina to bulge, bringing the focal plane closer to the pupillary plane and resulting in errors in habitual refraction. This means that visual stimuli that were previously in focus on the retina are now blurred. The degree of such retinal defocus may vary depending on the location on the retina. The effect of this defocus can be optically corrected as long as there is no damage to the retina. Optical effects and neurological effects must be distinguished in order to accurately identify potential visual function.

[0032] To distinguish optical effects from neurological effects, the devices and systems described herein for measuring potential visual function are particularly suitable for guiding the management of retinal diseases in clinical trials and evaluating the treatment of retinal diseases. The described devices and systems identify the main factors that affect the retina14 (see Figure 1), affect the measurement of visual function, and affect the potential vision obtained with treatment. The devices and systems include non-contact systems and do not require eye drops to dilate the pupil of the eyeball.

[0033] Referring to Figure 1, substantially all of a predetermined amount of light from a visual stimulus is projected through the pupil of the eyeball 16 along the illumination path 18. The focal plane 12 of the visual stimulus is the retina 14, the layer within the retina where visual acuity is particularly maximized. One of the main areas requiring attention when examining retinal function is the fovea 11, which provides the best visual acuity and color vision in a normal eyeball and is an important tissue in administrative assessments and clinical trial outcomes. To reach the retina, light must be focused by the cornea 26 and the lens 24, either of which may have lost transparency or had its optics degraded due to aging, disease, trauma, or adverse events related to treatment.

[0034] Several conditions can negatively affect the illumination path 18, such as the decrease in the amount of light reaching the retina due to pupillary constriction, which occurs naturally with age. Pupil size can also decrease as a result of other conditions, such as medications that constrict the pupil or neurological conditions. Furthermore, if the pupil size is greater than approximately 3 mm, it negatively affects the focus of both the illumination path 18 and the detection path 20 due to the changing focus across the pupillary plane.

[0035] Furthermore, depending on the condition of the cornea 26, lens 24, or any part of the anterior segment 22, light may not be able to pass through them completely. For example, the anterior segment may contain numerous locations or areas with tissue changes or aberrations, which can alter normal ocular function and may result in undesirable light scattering due to pathological conditions or aging, or other aberrations and lack of transmittance. Both the amount of light reaching the retina and the precision of the focus affect the measurement of visual function.

[0036] The presence of a small pupil that restricts light can result in inaccurate rendering of information about the retina. The cornea 26, lens 24, or other locations in the anterior segment 22 may have reduced transmittance or be unable to focus light onto the retina 14. The structure of the retina 14 may be altered by disease or trauma, resulting in retinal elevation, shortening the distance between elevated structures and bringing them too close to the cornea 26, preventing optimal focusing at one or more locations. All of these factors can also degrade the quality of the image of the retina 14 captured along the detection path 20 when light must pass through them on its way to the imaging device. Images of the retina 14 under different conditions indicate the state of the retina 14, the trajectory of fixation, and the stability of fixation by comparing retinal landmarks with the positions of visual stimuli projected through the pupil 16. The retinal image determines the relative position of the visual stimuli with the fovea 11 or other locations on the retina 14.

[0037] Figure 2 shows one embodiment of the optical imaging visual display system 40 according to the present invention. The near-infrared (NIR) imager 60 directs light towards the eyeball 10, directing the light towards the retina and focusing thereon to provide an accurate image. Those skilled in the art will recognize that various different configurations can perform this function. In different embodiments, the NIR imager is a point-scanning system or a line-scanning system, such as the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) by Elsner et al., 1992; U.S. Patent No. 7,331,669, U.S. Patent No. 7,831,106, or U.S. Patent No. 8,237,835; and the Eidon Camera (iCare, Vantaa, Finland). In a preferred embodiment, the NIR illumination is sufficiently dim so as not to interfere with the judgment used in visual function measurements. U.S. Patents 7,331,669, 7,831,106, and 8,237,835 are incorporated herein by reference in their entirety.

[0038] Light returning from the retina to the NIR imager 60 is focused onto the retina with sufficient precision to produce an image of the retina 14, providing a clearly focused and superior image for comparison with the position of a target projected onto the visible wavelength display 70. The illumination and detection characteristics of the NIR imager 60 provide both confocal and multiple scatter light imaging, as described in Elsner et al., 2020 or U.S. Patent No. 7,331,669, U.S. Patent No. 7,831,106, U.S. Patent No. 8,237,835, and U.S. Patent No. 8,488,895. The processor 100 includes one or more processors, including but not limited to computers, microcomputers, and electronically controlled devices. In different embodiments, the processor 100 includes memory for storing received data or includes a transmitter for transmitting data. In other embodiments, the memory or transmitter is located outside the processor 100. The processor 100 also controls the imager 60 via data acquisition and control lines 101 so that the characteristics of the NIR imager 60 enable imaging of both light transmitted through the eyeball and the characteristics of the sensor for the NIR imager 60. Image or image data parameters include, but are not limited to, intensity, gain, imaging mode, polarization characteristics, wavelength, width of illumination on the retina, or field of view of transmitted light waves, and are selectable by the operator. The operator adjusts the function of the imager 60 via control lines 102 through input devices such as a user interface 104 coupled to the processor 100 via control lines 102. The selected parameters are stored or recorded in the processor 100, its internal memory, or connected memory and used when determining visual function. As used herein, user interface means one or more devices that enable an operator or patient to interact with or control the system 40 by using visual displays of current or stored images, visualizations of stored data, results or normative values, voice or voice commands, touchscreen commands, user-selectable buttons, or other functions used to select, display or control test procedures or results based on current or stored information.

[0039] Similarly, a visible-wavelength display 70 controlled by the processor 100 via control line 106 transmits a light output directed toward the retina 14 in such a manner that a predetermined amount or type of light is directed into the eyeball 10 through the pupil 16. A visible-wavelength display controller 72 is connected between the processor 100 and the visible-wavelength display 70 to adjust the output of the visible-wavelength display. In other embodiments, the visible-wavelength display controller 72 is not included, and the processor 100 is configured to adjust the function of the visible-wavelength display controller 72. In one or more embodiments, the directional light is directed using a Maxwell field of view, also known as Köhler illumination, and is therefore directed in such a manner that the illumination on the retina 14 is identifiable, consistently reproducible, and constant from one eyeball to the next for either a single patient or multiple patients. In one embodiment, the display 70 includes, but is not limited to, a one-dimensional or two-dimensional display, including a digital optical projector, a liquid crystal display screen, liquid crystal on silicon, a cathode-emitting display, an electroluminescent display, a photoluminescent display, a plasma display panel, an incandescent display, a light-emitting diode, a combination thereof, or any similar optical display that projects a visual stimulus. In a different embodiment, the visual stimulus is one or more predetermined images stored in a memory located inside or outside the processor 100.

[0040] The processor 100 transmits commands via control lines 106, which control the displayed image on the display 70, to project visual stimuli generated or stored in memory, which include, but are not limited to, one or more patterns of visual stimuli, the intensity of the patterns, the timing of the displayed images, the motion of the images, the position of the display on the retina, and the color of the images. Additional visible or NIR illumination outputs for the wavefront measurement system 75, also controlled by the processor 100 via control lines 107, are combined with the light outputs from the visible wavelength display 70 by the beam shaper and combiner 130.

[0041] The processor 100 controls the parameters of the light source, i.e., the visible wavelength display 75, including but not limited to image, pattern, intensity, timing, motion, position on the retina, and color. The combined light output of the visible wavelength display 70 and the illumination of the wavefront measurement system 75 is directed to an adaptive optics unit 90, which includes one or more adjustable optical elements. The adjustment of the adaptive optics unit 90 is controllable by the adaptive optics controller 95 via control lines 105, resulting in a better focus of illumination on the retina 14 than would be achieved by correcting only the spherical and cylindrical surfaces. The adaptive optics controller 95 is controlled by the processor 100 via control lines 103. This combined light output is directed to the eyeball from the beam combiner 120 and combined with light from the NIR imager 60 in the beam combiner 110. Light from all three light sources—the illumination of the NIR imager 60, the visible wavelength display 70, and the wavefront measurement system 75—is directed through the pupil of the eyeball and focused onto the retina. The illumination of the visible wavelength display 70 and the wavefront measurement system is focused by the adaptive optical system 90. The NIR imager 60 is focused by its internal components via control from a processor 100 that communicates with both the NIR imager 60 and the wavefront measurement system 80. Light returning from the retina 14 passes through the pupil 16 of the eyeball 10. The amount of light projected through the pupil is calculated from wavefront measurement data, NIR image intensity, or other characteristics of image data or measurements from the patient's retina. In addition, the properties of the light returning from the eyeball and analyzed by the processor include, but are not limited to, fluorescence, coherence, or polarization, and are included collectively at each location or over a broader area.

[0042] U.S. Patent No. 7,416,305 by Williams et al. (Williams et al.) is distinguished from the present invention in that Williams requires that the image of the retina be a high-resolution image that is improved by the adaptive optics to provide a higher contrast image than the image received from the retina without the adaptive optics. However, in this disclosure, the image of the retina does not need to be a high-resolution image, nor does the received image need to be improved by the adaptive optics. According to Williams et al., the adaptive optics function as an adaptive optics device that uses calculated wave aberrations to provide a high-resolution, high-contrast image of the retina. In contrast, the adaptive optics 90 of this disclosure improve the quality of the visual stimulus on the retina and operate without altering the retinal imager NIR imager 60.

[0043] Patients with foveal retinal damage often use fixation points located periphery of the fovea, thus demonstrating the need for objective optical system correction for visual function tests based on the fixation point location. Furthermore, when examining peripheral vision, the visual stimulus is away from the fovea. Generally, the fovea is the location where a normal eye would fixate during visual function tests, but in patients with retinal damage, the fixation point is often away from the fovea. Optical errors corresponding to this position are unlikely to be recorded in previous ophthalmic or refractive tests. Measuring these off-axis optical errors by subjective refraction is difficult. However, conventional techniques have demonstrated that improving focus through the use of adaptive optical systems enhances the performance of visual function tests in both foveal-based (on-axis) and eccentric (off-axis) vision, where the visual stimulus is fixed at the fovea. Rossi et al. (2007) and Lewis, P., Baskaran, K., Rosen, R., Lundstrom, L., Unsbo, P., and Gustafsson, J. (2014). Objectively determined refraction improves peripheral vision. Optometry and vision science: official publication of the American Academy of Optometry, 91(7), 740-746, respectively. In particular, Lewis et al. teach the importance of using objectively determined refraction for peripheral vision function. However, wavefront aberrations at these eccentric positions cannot be measured with retinal imaging equipment with a narrow field of view unless the equipment is directed to a specific position and held in a precise position during optical measurement. Unless a wider field of view, video-rate retinal imaging is used, this positioning and accurate optical measurement are difficult due to patient eye movements. The requirement for measurement over a wide range of potential locations and precise positioning is one of the differences from Williams' U.S. Patent No. 7,416,305, which describes a single retinal imaging device with high resolution and only one wavefront measurement system.This system cannot perform detailed wavefront measurements across a sufficiently wide retinal area while maintaining precise positioning to support use in eccentric gaze. At the extreme of high resolution, diffraction-limited imaging is possible in the human retina, but its field of view is limited to at most about 2 degrees in an eye with a normal optical system. The methods described by Burns et al. (2019) and colleagues, and earlier by Williams, do not have retinal imaging systems with high-resolution images across the location of the eccentric fixation point, or with a field of view wide enough to use adaptive optics for examining peripheral visual stimuli.

[0044] Therefore, this disclosure does not rely on a single feature arising from imaging of the eyeball. Instead, a combination of perceived features, including, but not limited to, wide-field-of-view retinal imaging features, is used to determine the position and stability of the fixation point in combination with wavefront measurements. High-resolution images with wave aberration compensation, such as those of Williams, do not provide the kind of information used in this disclosure. For example, in Williams, the size of the retinal image in which optical compensation can be achieved must be limited to isoplanar patches that are too small in area to localize the fixation point if the patient has fixation sway or uses eccentric vision, as described above. Small retinal regions also provide incomplete information regarding retinal landmarks or retinal conditions. Therefore, Williams' method cannot be used because the field of view of the high-resolution images produced by Williams is too small.

[0045] In addition, the use of high-resolution retinal images hinders the use of multiple scattered light to generate the retinal image, because high spatial frequency information in the image is primarily found in light passing through the confocal aperture rather than being rejected. Furthermore, while the invention incorporates improvements in visual stimulation on the retina into a statistical framework, i.e., a statistical model, for determining potential performance in visual function tests and limitations imposed by optical or other factors, Williams' invention is directed toward implementation for use in refractive surgery or for manufacturing contact lenses that improve real-world vision beyond defocus and astigmatism. Finally, Williams specifies that the wavefront measurement technique is limited to point light sources for illumination and specifically uses the method of the Hartmann-Shack sensor. In contrast, this method is not limited to the Hartmann-Shack method as described by Liang and colleagues: Liang J, Grimm B, Goelz S, Bille JF in 1994. Objective measurement of wave aberrations of the human eye with the use of a Hartmann-Shack wave-front sensor. J Opt Soc Am(A)1994;11:1949~57. Examples of other methods include laser beam tracking and spatially resolved refractometers, compared to the Hartmann-Shack method.Moreno-Barriuso E, Marcos S, Navarro R, Burns SA. Comparing laser ray tracing, the spatially resolved refractometer, and the Hartmann-Shack sensor to measure the ocular wave aberration. Optom Vis Sci. March 2001;78(3):152-6.doi:10.1097 / 00006324-200103000-00007.PMID:11327676. The pyramidal wavefront detection method is, for example, Validation of a Clinical Aberrometer Using Pyramidal Wavefront Sensing by Singh NK, Jaskulski M, Ramasubramanian V, Meyer D, Reed O, Rickert ME, Bradley A, and Kollbaum PS. Optom Vis This is described in Sci. 2019 October;96(10):733-744.doi:10.1097 / OPX.0000000000001435.PMID:31592956.

[0046] In one embodiment, the present invention uses a point light source to illuminate the wavefront sensor, while in other embodiments, it uses a visible wavelength display 70 or a retinal image to calculate the required wavefront compensation. In other embodiments, other methods are used, such as a Hartmann-Shack sensor or a pyramidal wavefront detection method for correcting the focus of the visual display on the retina. The present invention also reports data from wavefront correction for use in statistical models to identify and clarify the causes of visual performance degradation used to calculate predicted performance.

[0047] NIR light returning from the eyeball 10 passes through the beam combiner 110 and is returned to the NIR imager 60, where an image of the retina 14 is formed. The fundus image, including the retinal image, is transmitted to the processor 100 via data acquisition and control lines 101 for storage and analysis. Since the coordinate positions of the projection of visible wavelength stimuli on the retina are known, the NIR image provides a means of registering the positions of visible wavelength stimuli on the retina with known retinal landmarks. These include, but are not limited to, retinal vessels, optic discs, periapical atrophy, foveal light reflex, atrophy, hemorrhage, neovascularization, epiretinal membranes, as well as gliosis, pigment changes, and polarization changes. This provides fixation trajectories, also known as eccentricity, and variability of fixation trajectories, also known as fixation sway. The retinal image further provides information about the state of the retina at the position on the retina that the visible wavelength display is focusing on. Fixation information and retinal state information regarding the position of visual stimuli on the retina are displayed as a graphic overlay, numerically stored by the computer as a numerical database, or both, using the processor 100 and the user interface 104.

[0048] Light returning from the eyeball 10, which is not intended to be directed to the NIR imager 60, is directed away from the beam combiner 110 to the beam combiner 120. Light in the wavelength range from the visible or NIR illumination of the wavefront measurement system 75 is directed to the visible or NIR wavefront measurement system 80, which provides data to the processor 100 via the data acquisition and control line 108 to quantify the optical aberrations of the light returning from the retina 14 measured at the pupil plane 22. In other embodiments, image data from different illumination wavelengths other than NIR or long-wavelength visible illumination is directed to the processor. The wavefront measurement system 80 also communicates hardware and / or software-related data to the processor 100 via the data acquisition and control line 108, including but not limited to timing, gain, the number of samples included in each measurement, and the position of the samples included in each measurement, to enable precise control of the wavefront measurement system 80 by the processor 100, whether controlled by the measurement under the processor's commands or by post-processing following the acquisition of data transmitted to the processor. This wavefront measurement data is optimized by processor 100 to provide sufficiently accurate information for focusing visual stimuli onto the retina, while ensuring that the environment is sufficiently dim or that no visible illumination is simultaneously introduced that would interfere with the measurement of visual function.

[0049] The control loop of the adaptive optical system 90 is formed by the wavefront measurement system 80, the processor 100, the adaptive optical system controller 95, and the adaptive optical system 90, based on the measurement of the illumination focus of the wavefront measurement system 75 on the retina 14. Wavefront aberrations are calculated, and those that can be corrected by the adaptive optical system are identified, recorded, and stored as data in a database. Furthermore, those that cannot be corrected, or are not practical to correct, and which leave optical errors, are identified, recorded, and stored as data.

[0050] Certain types of aberrations, namely very high-order aberrations, are not easily correctable and do not require acceptable visual correction. This disclosure provides a cost-effective solution that eliminates large visual errors and quantifies residual errors that are often not correctable at all or not correctable at an acceptable price. Consequently, this disclosure does not aim for the best focus ever achieved, which would not be achievable with eyeglasses in the real world, is difficult to provide with contact lenses, or is even difficult to provide with intraocular lens implants (IOLs). Therefore, in one or more embodiments, this disclosure uses mirrors and optical designs to provide correction of low-order aberrations and some higher-order wavefront errors. In some embodiments, adaptive optics are utilized, which move sufficiently to tilt the imaging rays and return them to where they should be directed. The excessive cost of fine-tuning many mirrors makes the correction of very high-order aberrations impractical, some of which change rapidly over time with the tear film.

[0051] The response mechanism 150 reports the patient's judgment regarding the visible wavelength stimulus, including but not limited to whether the target was visible, the direction the letters were pointing, and the color, and provides input to the processor. In one embodiment, the response mechanism 150 is operated by the patient. In another embodiment, the response mechanism is a user interface 104 for an operator to input the patient's response.

[0052] The determination of whether the target is being seen correctly is then used by the processor 100 to control the next visible wavelength stimulus for measuring visual function. This next visible wavelength stimulus is based, in one or more embodiments, on the patient's response or a predetermined sequence. A database 200 communicating with the processor 100 stores current responses, past responses, and any data related to the determination of visual function. The processor 100 further processes the retinal image from the NIR imager 60 received via the control line 101 to identify the state of the retina 14 at the target location. The state of the retina includes results from confocal imaging and multiple scattered light imaging, and indicates changes in signal amplitude indicating irregular retinal or subretinal absorption due to blood or pigment defects, and calculations indicating elevation or thickening of subretinal structures, or the movement of blood cells or other particles through blood vessels. Database 200 includes results from the system, including retinal images, the position of targets on the retina, fixation stability, results from retinal image processing from retinal image data or artificial intelligence, retinal state, retinal state at target position, results from measured visual function including both central tendency and variability, uncorrected wavefront error, and correctable vs. uncorrectable wavefront error.

[0053] The database also includes, but is not limited to, other relevant clinical and demographic data, including retinal conditions from other instruments such as color fundus photographs, scanning laser ophthalmoscopy, vascular maps from scanning laser ophthalmoscopy, optical coherence tomography, optical coherence tomography angiography, or any of these used with adaptive optics, wavefront aberration or optical measurements from other instruments, age, sex, diagnosis, treatment history, and results from other measurements of visual function.

[0054] Model 210 communicates with processor 100 and uses data stored in database 200 to provide statistical estimates of central tendency and variability of visual function, thereby quantifying the potential range of vision that can be achieved. Central tendency is a single value that attempts to describe a dataset by identifying its central position within that dataset. This includes factors unrelated to optical factors, such as small pupils, corneal or tear film optics defects, cataract lenses, inaccurate focal planes due to refractive errors, and other factors, some of which can be mitigated during measurements by the disclosed system to more accurately determine the condition of the retina and the potential for improvement through treatment. In one embodiment, the metric for central tendency is the mean, and the metric for variability is the variance, providing statistical limits of the significance of confounding reasons for vision loss in the form of upper and lower confidence limits, which can be set according to a certain probability, e.g., the probability of falling outside the confidence limit by only a 95% confidence limit. Furthermore, reporting from wavefront errors shows how visual measurements are limited in cataracts.

[0055] The proprietary statistical analysis combines information from the various sources mentioned above to draw boundaries on predicted performance. For example, to address the potential visual acuity that a particular eyeball may achieve with retinal treatment, the boundaries are determined from confidence limits derived from central trends (predictions) and variability, including optical errors, fixation point data, and other data. The upper and lower limits of potentially achievable visual acuity are determined using aberrations that have been measured and found to be correctable. For example, in LogMAR measurements based on visual acuity measurements, one method includes tumbling E and four alternative forced selections. The statistical analysis includes determining whether optical, neurological, and other factors are independent or must be modeled as interacting with each other. A key aspect of the model is the inclusion of a set of data to determine whether the variables are independent and whether the overall variance is equal to the sum of the variances of the individual factors. The system quantifies this state, including whether the predicted visual acuity in the event of successful retinal treatment, or whether the exclusion of irrelevant factors such as lens opacity, can be achieved.

[0056] Conversely, in different embodiments, the model requires a function beyond a simple sum of the variances of two or more variables that must be used to calculate the predicted visual function performance after optical factors have been corrected. Furthermore, each variable may have a function more complex than a Gaussian distribution, and the variances may be distributed in a manner that is not symmetrical around the mean and does not scale linearly with respect to the mean. The combined variances are used to calculate the upper and lower confidence limits. These confidence limits, i.e., the boundaries used to interpret the visual function test scores, will be broader or narrower depending on the function that combines the values ​​of the constituent factors and their variances. The upper limit, by definition, corresponds to the value that the visual function measurement must exceed for retinal treatment to be considered successful or to be counted as an improvement in long-term measurements. The lower limit, by definition, corresponds to the value that visual function must exceed or to be considered not to have deteriorated in follow-up. The lower limit is also the value that visual function must exceed for treatment to be considered effective when the goal is to maintain vision over time. These values ​​may be relevant to current metrics such as lines of vision gain or loss, lacking important assessments of optical effects, gaze stability, or other factors.

[0057] The present invention has the following features: 1) Provides evaluation of fixation position using video-rate and patient-invisible near-infrared retinal imaging. 2) Provides evaluation of gaze stability using the same video-rate near-infrared retinal imaging. 3) Identifies optical errors of the patient's eyeball, not limited to spherical and cylindrical, including those resulting from pathological or age-related conditions in the cornea, lens, or pupil, collected by wavefront sensor measurements of light returning from the retina. 4) Provides objective correction during visual function measurement of major optical errors of the patient's eyeball, not limited to spherical and cylindrical, using the wavefront measurements described in item 3 above with an adaptive optical system. 5) Projects a visual target onto the retina through a fixed-size pupil of the instrument to reduce large variability due to individual differences in pupil size. 6) Provides analysis of retinal images using confocal and multiple scatter light, and different imaging modes, as described in U.S. Patent Nos. 7,331,669, 7,831,106, 8,237,835, and 8,488,895, to clarify the state of the retina at that location and detail precise lesions at fixation points used by patients in visual examinations by using a combination of information from confocal or multiple scatter light imaging and different imaging modes. 7) Provides a novel system for measuring potential vision, including combinations of all the above components 1-6, using proprietary statistical analysis.

[0058] Figure 3 shows another embodiment of the optical imaging visual display system 50 according to the present invention. The near-infrared (NIR) imager 60, i.e., the imaging device, directs light towards the eyeball 10, directing the light towards the retina and focusing thereon to provide an accurate image. Those skilled in the art will recognize that various different configurations perform this function. In different embodiments, the NIR imager is a point-scanning system or a line-scanning system, such as those described by Elsner et al., 1992; and the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany); and U.S. Patent No. 7,331,669, U.S. Patent No. 7,831,106, or U.S. Patent No. 8,237,835; and the Eidon Camera (iCare, Vantaa, Finland). The imaging device 60 illuminates the retina by scanning illumination across the retina or by projecting a series of illumination areas onto the retina, and the light from the retina is detected synchronously. In one embodiment, the imaging device 60 has a wide field of view, i.e., a field of view angle of about 8 to 60 degrees, to enable eccentric fixation and determination of retinal landmarks. Light returning from the retina to the NIR imager 60 is focused onto the retina with sufficient precision to produce an image of the retina 14, providing a clearly focused and excellent image for comparison with the position of a target projected on a visible wavelength display 70. The illumination and detection characteristics of the NIR imager 60 provide both confocal and multiple scatter light imaging, as described by Elsner et al., 2020. The image or data used to compute the image is directed to a processor 100, which consists of one or more processors including a computer, microcomputer, and electronic control devices. In different embodiments, the processor 100 includes memory for storing received data or includes a transmitter for transmitting data. In other embodiments, the memory or transmitter is located outside the processor 100. The processor 100 also controls the imager 60 via data acquisition and control lines 101 so that the characteristics of the NIR imager 60 enable imaging of both light passing through the eyeball and the characteristics of the sensor for the NIR imager 60.The characteristics include, but are not limited to, intensity, gain, imaging mode, polarization characteristics, wavelength, width of illumination on the retina, or field of view of transmitted light waves, and are selectable by the operator. The operator adjusts the functions of the imager 60 via the control line 102 through an input device such as a user interface 104 coupled to the processor 100 via the control line 102. The selected parameters are stored or recorded in the processor 100 and used when determining visual function.

[0059] Similarly, a visible wavelength display 70 controlled by the processor 100 via control line 106 has a light output directed toward the retina 14 in such a manner that it directs a known amount and known type of light into the eyeball 10 through the pupil 16. In one or more embodiments, the directional light is directed using a Maxwell field of view, also known as Köhler illumination, and is therefore directed in such a manner that the illumination on the retina 14 is identifiable, consistently reproducible, and constant from one eyeball to the next for either a single patient or multiple patients. In one embodiment, the display 70 includes, but is not limited to, a one-dimensional or two-dimensional display, including a digital light projector, a liquid crystal display screen, liquid crystal on silicon, a cathode-emitting display, an electroluminescent display, a photoluminescent display, a plasma display panel, an incandescent display, a light-emitting diode, a combination thereof, or any similar optical display that projects a visual stimulus. In different embodiments, the visual stimulus is one or more predetermined images stored in a memory located inside or outside the processor 100. As used herein, a one-dimensional display transmits a single line that is scanned across the retina.

[0060] The processor 100 transmits commands via control lines 106, which control the image displayed on the display 70, to project visual stimuli generated or stored in memory, which include, but are not limited to, the pattern of the visual stimulus, the intensity of the pattern, the timing of the displayed image, the motion of the image, the position of the display on the retina, and the color of the image. The output of the visible wavelength display 70 transmits light to the adaptive optics unit 90 via beam shaping and combiner components 135, where wavefront errors are corrected by one or more adjustable optical elements. The adaptive optics unit 90 is controlled by the adaptive optics controller 95 via control lines 105. The adaptive optics controller 95 is controlled by the processor 100 via control lines 103.

[0061] The adaptive optics system 90 can be controlled by the adaptive optics system controller 95 via control lines 105, resulting in a better focus of illumination on the retina 14 than would be achieved by correcting only the spherical and cylindrical surfaces. This combined light output is directed to the eyeball from a mirror, beam splitter, or filter 125 and combined with light from the NIR imager 60 in the beam combiner 110. Light from both the NIR imager 60 and the visible wavelength display 70 is directed through the pupil of the eyeball and, together with the visible wavelength display 70, is focused onto the retina by the adaptive optics system 90. The NIR imager 60 is focused by its internal components via control from a processor 100 communicating with the NIR imager 60. The light returning from the retina 14 passes through the pupil 16 of the eyeball 10.

[0062] NIR light returning from the eyeball 10 passes through the beam combiner 110 and is returned to the NIR imager 60, where an image of the retina 14 is formed. The fundus image, including the retinal image, is transmitted to the processor 100 via data acquisition and control lines 101 for storage and analysis. Since the coordinate positions of the projection of visible wavelength stimuli on the retina are known, as described above, the NIR image provides a means for registering the positions of visible wavelength stimuli on the retina with known retinal landmarks. This provides fixation trajectories, also known as eccentricity, and variability of fixation trajectories, also known as fixation sway. The retinal image further provides information about the state of the retina at the position on the retina that the visible wavelength display is focusing on. The fixation information and retinal state information regarding the position of visual stimuli on the retina are displayed as graphic overlays, numerically stored in the computer, or both, using the processor 100 and the user interface 104.

[0063] Light returning from the eyeball 10, which is not intended to be directed to the NIR imager 60, is directed away from the beam combiner 110 to a mirror, beam splitter, or filter 125. The NIR imager 60 also provides data to the processor 100 via data acquisition and control lines 101 to quantify the optical aberrations of the light returning from the retina 14. This is known as a sensorless adaptive optical system because the NIR imager 60 includes illumination and sensors, but does not have additional illumination sources and sensors (Burns et al., 2019). In one embodiment, the location of a target on the retina is used by the processor 100 to limit the optical correction data to a sample of that location, which is more accurate than averaging over a portion of the retina that includes areas outside the area from which the visual stimulus is projected, for example, because the height of the retina may vary. Since the present invention is not limited to the narrow field of view of the retina, which is an inherent limitation of Williams et al., the area of ​​the retina sampled can be optimized to provide a precise focus on a specific location on the retina.

[0064] In this invention, pathological features of the retina can be identified, which is important because such pathological features can alter the preferred focal plane on the retina 14 during a visual function test at one retinal location compared to that at another retinal location. In another embodiment, the wavefront error is pre-calculated from either another device or a measurement of visual acuity that a particular eyeball can potentially achieve, and the target position on the retina determined by the NIR imager is used by the processor 100 to specify the wavefront error correction, which is then transmitted via control line 103 to the controller 95 of the adaptive optics. In one embodiment, signal enhancement for wavefront error calculation is generated by using structured illumination, as described by Clark et al., 2010, 2011; Elsner et al., 2011. This is achieved whether the NIR imager is a point scanning system or a line scanning system, as described by Elsner et al. in 1992; the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany); U.S. Patent No. 7,331,669, U.S. Patent No. 7,831,106, or U.S. Patent No. 8,237,835; and the Eidon Camera (iCare, Vantaa, Finland). The latter allows for low-cost and rapid switching of illumination lines on and off, which provides a rectangular wave diffraction grating that facilitates Fourier analysis and other analyses of light transmission through the eyeball for sampling from a region of interest on the retina. The amount of light returned from the retina by the NIR imager 60 depends on the pupil diameter because it is hardly affected by fundus pigment deposition, thereby reporting the patient's pupil diameter in the absence of the wavefront measurement system in Figures 2, 4, and 5, as described by Elsner et al. in 2013.

[0065] The control loop of the adaptive optics system 90 is formed by the NIR imager 60 or data in the database 200, the processor 100, the adaptive optics controller 95, and the adaptive optics system 90, based on focal point measurements from the NIR imager 60 on the retina 14. Wavefront aberrations are calculated and reported to be correctable by the adaptive optics system, as well as those that are not correctable or are not practical to correct, resulting in residual optical system errors. In one embodiment, the illumination of the NIR imager 60 is temporally modulated, and then a frequency-based detection scheme in the detection mechanism of the NIR imager 60 is used to achieve an improved signal-to-noise ratio. Alternatives include simple flicker of illumination, as well as more complex frequency-based homodyne and heterodyne detection by the NIR imager 60. In one embodiment, NIR illumination for wavefront measurement is temporally alternating with a pattern of NIR illumination used to generate a more optimal retinal image for determining the retinal position, fixation sway, or retinal condition of a visual target. In a preferred embodiment, the NIR illumination is sufficiently dim so as not to interfere with the judgment made by the patient used in visual function measurements. In a preferred embodiment, data from focus and wavefront error calculations are reported in a manner that describes lower-order and higher-order aberrations resulting from wavefront errors, as well as estimation errors of the retinal focus. The response mechanism 150 reports judgments made by the patient regarding the visible wavelength stimulus perceived by the patient, including but not limited to whether a target was seen, the direction the letter was pointing, and the color, and provides input to the processor. In one embodiment, the response mechanism is operated by the patient. In another embodiment, the response mechanism is a user interface 104 for an operator to input the patient's responses.

[0066] The determination of whether the target is seen correctly, i.e., correctly identified, is then used by the processor 100 to control the next visible wavelength stimulus for the measurement of visual function. The database 200, which communicates with the processor 100, stores current responses, past responses, and any data related to the determination of visual function. The processor 100 further processes the retinal image from the NIR imager 60 received via the control line 101 to identify the state of the retina 14 at the target location. The state of the retina includes results from confocal imaging and multiple scattered light imaging, and indicates changes in signal amplitude indicating irregular retinal or subretinal absorption due to blood or pigment defects, and calculations indicating elevation or thickening of subretinal structures, or the movement of blood cells or other particles through blood vessels. The database 200 stores the retinal image, the target on the retina This includes results from the system, including target position, fixation stability, retinal image from retinal image data or results from artificial intelligence processing, retinal state, retinal state at target position, results from measured visual function including both central tendency and variability, uncorrected wavefront error, and correctable vs. uncorrectable wavefront error.

[0067] Database 200 also includes, but is not limited to, other relevant clinical and demographic data, including retinal conditions from other instruments such as color fundus photographs, scanning laser ophthalmoscopic examinations, optical coherence tomography, optical coherence tomography angiography, or any of these used with adaptive optics, wavefront aberrations or optical measurements from other instruments, age, sex, diagnosis, treatment history, and results from other measurements of visual function. These data can be used to improve the calculation of wavefront errors.

[0068] Model 210 communicates with processor 100 and uses data stored in the database to provide statistical estimates of central tendency and variability of visual function, thereby quantifying the potential range of vision that can be achieved as described above. Central tendency is a single value that attempts to describe a dataset by identifying its central position within that dataset. This includes factors unrelated to optical factors, such as small pupils, corneal or tear film optics defects, cataracts, inaccurate focal planes due to refractive errors, and other factors, some of which can be mitigated during measurement by the disclosed system to more accurately determine the condition of the retina and the potential for improvement through treatment. Upper and lower limits of performance on the visual task are calculated and used as in the embodiment of Figure 2.

[0069] Figure 4 shows another embodiment of the optical imaging visual display system 40 according to the present invention. The NIR imager 60, having some of the embodiments described above, directs light towards the eyeball 10 and directs the light towards the retina so that it is focused thereon, thereby providing an accurate image. The function is similar to that of Figures 2 and 3, with the exception of the specific modifications described.

[0070] Light returning from the retina to the NIR imager 60 is focused onto the retina with sufficient precision to produce an image of the retina 14, providing a clearly focused and superior image for comparison with the position of a target projected onto the visible wavelength display 70. As described in Elsner et al., 2020 and in other descriptions of Figure 2, the illumination and detection characteristics of the NIR imager 60 provide both confocal and multiple scatter light imaging. The image or data used to compute the image is directed to a processor 100, which consists of one or more processors including a computer, microcomputer, and electronic control devices. In different embodiments, the processor 100 includes memory for storing received data or includes a transmitter for transmitting data. In other embodiments, the memory or transmitter is located outside the processor 100. The processor 100 also controls the imager 60 via data acquisition and control lines 101 so that the characteristics of the NIR imager 60 enable imaging of both light transmitted through the eyeball and the characteristics of the sensor for the NIR imager 60. The characteristics include, but are not limited to, intensity, gain, imaging mode, polarization characteristics, wavelength, width of illumination on the retina, or field of view of transmitted light waves, and are selectable by the operator. The operator adjusts the functions of the imager 60 via the control line 102 through an input device such as a user interface 104 coupled to the processor 100 via the control line 102. The selected parameters are stored or recorded in the processor 100 and used when determining visual function.

[0071] Similarly, a visible wavelength display 70 controlled by the processor 100 via control line 106 has a light output directed toward the retina 14 in such a manner that it directs a known amount and known type of light into the eyeball 10 through the pupil 16. In one or more embodiments, the directional light is directed using a Maxwell field of view, also known as Köhler illumination, and is therefore directed in such a manner that the illumination on the retina 14 is identifiable, consistently reproducible, and constant from one eyeball to the next for either a single patient or multiple patients. In one embodiment, the display 70 includes, but is not limited to, a one-dimensional or two-dimensional display, including a digital light projector, a liquid crystal display screen, liquid crystal on silicon, a cathode-emitting display, an electroluminescent display, a photoluminescent display, a plasma display panel, an incandescent display, a light-emitting diode, a combination thereof, or any similar optical display that projects a visual stimulus. In different embodiments, the visual stimulus is one or more predetermined images stored in a memory located inside or outside the processor 100.

[0072] The processor 100 sends commands via control lines 106 that control the image displayed on the display 70 to project visual stimuli generated or stored in memory, which include, but are not limited to, the pattern of the visual stimulus, the intensity of the pattern, the timing of the displayed image, the motion of the image, the position of the display on the retina, and the color of the image.

[0073] The light output of the visible wavelength display 70 is directed by a beam shaper and combiner 135 to an adaptive optics unit 90 which includes one or more adjustable optical elements. The adjustment of the adaptive optics unit 90 is controllable by a controller 95 of the adaptive optics unit via a control line 105, and as a result, the focus of illumination on the retina 14 is better than that achieved by correcting only the spherical and cylindrical surfaces. The controller 95 of the adaptive optics unit is controlled by a processor 100 via a control line 103. This light output is directed from a beam combiner 120 to the eyeball, where it is combined with light from the NIR imager 60 in a beam combiner 110. Light from both the NIR imager 60 and the visible wavelength display 70 is directed through the pupil of the eyeball and, together with the visible wavelength display 70, is focused onto the retina 14 by the adaptive optics unit 90. The NIR imager 60 is focused by its internal components via control from a processor 100 which communicates with both the NIR imager 60 and the wavefront measurement system 80. Light returning from the retina 14 passes through the pupil 16 of the eyeball 10.

[0074] NIR light returning from the eyeball 10 passes through the beam combiner 110 and is returned to the NIR imager 60, where an image of the retina 14 is formed. The fundus image, including the retinal image, is transmitted to the processor 100 via data acquisition and control lines 101 for storage and analysis. Since the coordinate positions of the projection of visible wavelength stimuli on the retina are known, the NIR image provides a means of registering the positions of visible wavelength stimuli on the retina with known retinal landmarks. These include, but are not limited to, retinal vessels, optic discs, periapical atrophy, foveal light reflex, atrophy, hemorrhage, neovascularization, epiretinal membranes, as well as gliosis, pigment changes, and polarization changes. This provides fixation trajectories, also known as eccentricity, and variability of fixation trajectories, also known as fixation sway. The retinal image further provides information about the state of the retina at the position on the retina that the visible wavelength display is focusing on. Fixation information and retinal state information regarding the position of visual stimuli on the retina are displayed as a graphic overlay, numerically stored in a computer, or both, using the processor 100 and the user interface 104. Light returning from the eyeball 10, which is not intended to be directed to the NIR imager 60, is directed away from the beam combiner 110 to the beam combiner 120. Light in the wavelength range from the visible wavelength display 70 is directed via data acquisition and control lines 108 to a visible or NIR wavefront measurement system 80 that provides data to the processor 100, quantifying the optical aberrations of the light returning from the retina 14 measured at the pupillary plane 22. The wavefront measurement system 80 also communicates hardware and / or software-related data to the processor 100 via data acquisition and control lines 108, including but not limited to timing, gain, the number of samples included in each measurement, and the positions of the samples included in each measurement, to enable precise control of the wavefront measurement system 80 by the processor 100, whether controlled by measurements under the processor's commands or by post-processing following the acquisition of data transmitted to the processor.

[0075] The control loop of the adaptive optics system 90 is formed by the wavefront measurement system 80, processor 100, adaptive optics controller 95, and the adaptive optics system 90, based on the measurement of the focus of illumination from the visible wavelength display 70 on the retina 14. Wavefront aberrations are calculated and those that can be corrected by the adaptive optics system are reported, as are those that cannot be corrected or are not practical to correct, resulting in residual optical system errors. In one embodiment, the illumination from the visible wavelength display 70 is temporally modulated, and then a frequency-based detection scheme in the detection mechanism of the visible or NIR wavefront measurement system 80 is used to achieve an improved signal-to-noise ratio. Alternatives include simple flicker of illumination, as well as more complex schemes of homodyne and heterodyne detection by the frequency-based visible or NIR wavefront measurement system 80. In one embodiment, the illumination for wavefront measurement is temporally alternating with a pattern used to examine visual function. In a preferred embodiment, the NIR illumination of the NIR imager 60 is sufficiently dim so as not to interfere with the judgment used in visual function measurement. Similarly, in one preferred embodiment, the NIR illumination of the NIR imager 60 does not overlap with the wavelength range of the visible wavelength display 70 so as not to interfere with either the wavefront measurements or the visual function measurements. In a preferred embodiment, data from focus and wavefront error calculations are reported in a manner that describes the lower and higher-order aberrations resulting from the wavefront error, as well as the estimation error of the retinal focus.

[0076] The response mechanism 150 reports the patient's judgment regarding the visible wavelength stimulus, including but not limited to whether the target was visible, the direction the letters were pointing, and the color, and provides input to the processor. In one embodiment, the response mechanism 150 is operated by the patient. In another embodiment, the response mechanism is a user interface 104 for an operator to input the patient's response.

[0077] The determination of whether the target is being seen correctly is then used by the processor 100 to control the next visible wavelength stimulus for measuring visual function. This next visible wavelength stimulus may be based on the patient's response or a predetermined sequence of visual targets. A database 200 communicating with the processor 100 stores current responses, past responses, and any data related to the determination of visual function. The processor 100 further processes the retinal image from the NIR imager 60 received via the control line 101 to identify the state of the retina 14 at the target location. The state of the retina includes results from confocal imaging and multiple scattered light imaging, and indicates changes in signal amplitude indicating irregular retinal or subretinal absorption due to blood or pigment defects, and calculations indicating elevation or thickening of subretinal structures, or the movement of blood cells or other particles through blood vessels. Database 200 includes results from the system, including retinal images, the position of targets on the retina, fixation stability, results from retinal image processing from retinal image data or artificial intelligence, retinal state, retinal state at target position, results from measured visual function including both central tendency and variability, uncorrected wavefront error, and correctable vs. uncorrectable wavefront error.

[0078] The database also includes, but is not limited to, other relevant clinical and demographic data, including retinal conditions from other instruments such as color fundus photographs, scanning laser ophthalmoscopic examinations, optical coherence tomography, optical coherence tomography angiography, or any of these used with adaptive optics; wavefront aberrations or optical measurements from other instruments; age, sex, diagnosis, treatment history, and results from other measurements of visual function. Model 210 communicates with processor 100 and uses the data stored in the database to provide statistical estimates of central tendency and variability of visual function, so that the range of potential vision that may be realized, as described above, is quantified. Central tendency is a single value that attempts to describe a dataset by identifying its central position within that dataset. This also includes factors unrelated to optical factors, such as small pupils, poor corneal or tear film optics, cataracts, inaccurate focal planes due to refractive errors, and other factors, some of which can be mitigated during measurements by the disclosed system to more accurately determine the condition of the retina and the potential for improvement through treatment. In one embodiment, the metric for central trend is the mean, the variance is the variance, and the statistical limits of the significance of confounding reasons for visual impairment are provided in the form of upper and lower confidence limits, which can be set according to a specific probability, e.g., the probability of falling outside the confidence limit by only a certain probability, e.g., the 95% confidence limit. Furthermore, reporting from wavefront errors shows how the visual measurements are limited in cataracts. The upper and lower limits of performance on the visual task are calculated and used as in the embodiment of Figure 2.

[0079] Figure 5 shows another embodiment of the optical imaging and visual display system 40 for determining visual function while performing optical aberration measurements using wavefront measurements with a Hartmann-Shack sensor. The NIR or visible wavelength imager 64 is shown as a digital optical projector (DLP) comprising a digital mirror (DMD) and an illumination source which is a vertical-cavity surface-emitting laser (VCSEL) as seen in Muller MS and Elsner AE. Confocal Retinal Imaging Using a Digital Light Projector with a Near Infrared VCSEL Source. Proc SPIE Int Soc Opt Eng. February 2018; 10546:105460G. doi:10.1117 / 12.2290286. PMID:29899586; PMCID:PMC5995569. In this embodiment, a visible wavelength display 74 using a separate DLP for illumination and pattern generation is directed to an adaptive optical system 90 by an additional focusing lens 250 under the control of a visible or NIR wavefront measurement system 82 for correcting wavefront aberrations to achieve precise focusing on the retina 14. Illumination from an NIR or visible wavelength imager 64 is combined with illumination from the visible wavelength display 74 using a series of lenses 250 and a beam combiner 120. The well-known Hartmann-Shack method is implemented using a visible or NIR wavefront measurement system 82, which evaluates the intensity and position of an array of points focused within the pupillary plane, generated by sampling light returning from the retina as it passes through a small lens array, as described by Burns et al. in 2019.

[0080] Figures 6A, 6B, 6C, and 6D show sample graphs of low-order aberrations (LOA) and higher-order aberrations (HOA) from NIR wavelength measurements, illustrating the effects of aging and refractive error. This also demonstrates that the pyramidal wavefront detection method can be used in the present invention. That is, the method for measuring wavefront aberrations is not limited to the Hartmann-Shack method. Figure 6A in the upper left shows the results obtained from the eye of a 30-year-old patient, who is emmetropic but has some astigmatism, and is therefore expected to have minimal low-order aberrations (280). Figure 6B in the upper right shows the results obtained from the eye of a 30-year-old patient, who is emmetropic and has some astigmatism, but is expected to have minimal age-related changes in the lens, and is therefore expected to have minimal higher-order aberrations (281). Figure 6C in the lower left shows the results from the eye of a 71-year-old patient, who is myopic and is therefore expected to have large low-order aberrations (282). Figure 6D in the lower right shows the results from the eye of a 71-year-old patient, who is myopic and is expected to have age-related changes in the lens and tear film, and therefore is expected to have larger higher-order aberrations (283). The plot on the left shows astigmatism (vertical), defocus, astigmatism (overall), tilt (horizontal), tilt (vertical), and piston. The plot on the right shows quadrafoil (vertical), astigmatism (vertical), spherical aberration, astigmatism (overall), trefoil (overall), coma (horizontal), coma (vertical), and trefoil (vertical).

[0081] Figures 7A and 7B illustrate another method for reporting wavefront aberration, showing the difference between young patients (Figure 7A) and elderly patients (Figure 7B) in the calculated deviation from the spot focused on the retina by the eyeball, known as the point image distribution function. The eyeball of the young patient (upper) has a more compact distribution of light on the retina and exhibits better focus. The eyeball of the elderly patient (lower) has a non-compact distribution and a function more complex than that produced by simple defocusing. In this case as well, the pyramidal wavefront detection method of the present invention, i.e., the method for measuring wavefront aberration, demonstrates that it is not limited to the Hartmann-Schuck method.

[0082] Figures 8A and 8B illustrate another method for reporting wavefront aberration and show the differences between young patients (Figure 8A) and elderly patients (Figure 8B) in the plot of wavefront aberration in the pupillary plane. In the upper young patient, i.e., Figure 8A, the wavefront is fairly constant across the entire pupil, while in the lower elderly patient, who is more myopic, i.e., Figure 8B, there is a significant difference between the central and peripheral regions of the pupil.

[0083] Figures 9A and 9B show the predicted degradation of contrast in the letter E due to wavefront aberration, comparing the eye of a young person with normal vision (Figure 9A) with the eye of an older person with myopia and increased higher-order wavefront aberration (Figure 9B). Since the letter E is predicted to be poorly focused on the retina of older patients, a decline in visual function is predicted even if the retina is healthy. In this case as well, we demonstrate that a pyramidal wavefront detection method is used in one or more embodiments. That is, the method for measuring wavefront aberration is not limited to the Hartmann-Schuck method.

[0084] While exemplary embodiments incorporating the principles of the present invention have been disclosed herein, the present invention is not limited to the disclosed embodiments. Rather, this application is intended to cover any variations, uses, or applications of the present invention using its ordinary principles. Furthermore, this application is intended to cover developments from this disclosure that are known or customary in the art to which the present invention relates and which fall within the scope of the appended claims.

Claims

1. A system for measuring the visual function of an eyeball with a pupil, while quantifying or minimizing factors that negatively affect vision but are unrelated to the condition of the retina, (a) A visual display having an optical design that projects light onto the retina through the pupil of the eyeball, and allows most of the light to pass through the pupil, thereby accurately transmitting visual stimuli including high spatial frequency or low contrast, while eliminating individual differences in the amount of light reaching the retina; (b) A processor configured to receive fundus images, wherein the fundus images include one or more retinal images, each containing details based on one or more states of the retinal structure, subretinal structure, or fixation point trajectory. (c) The processor is configured to compare the visual stimulus from the visual display with one or more retinal images to provide the trajectory of the retinal target, which is known as the trajectory of a fixation point and, in other fields, known as the eccentric field of view. (d) The processor is configured to receive wavefront measurements for evaluating the visual function being tested based on the deviation of the wavefront of the light reaching the retina at the location of the visual stimulus in the plane of the pupil of the eyeball, (e) The processor determines the wavefront error arising from the optical system of the eyeball from the wavefront measurement value, (f) A control mechanism that controls one or more adaptive optical systems to correct the wavefront error of the visual display and improve the focus of the visual stimulus on the retina, (g) The processor adjusts the focus of the visual stimulus on the retina based on the wavefront measurement, evaluates corrected and uncorrected wavefront aberrations, (h) A response mechanism for recording a judgment regarding the visual stimulus, (i) The control mechanism controls one or more parameters of the visual stimulus of the visible wavelength display, (j) The processor calculates the parameters used in the visual display or final output according to the results of b, c, d, e, g, h, and i, (k) The visual function measurements include a predicted value for visual acuity in the event of successful retinal treatment or removal of unrelated factors such as lens opacity, and (l) The processor provides visual function metrics including a central tendency scale and variability, identifies an upper limit that must be exceeded to conclude that the retinal condition is improving, and includes a lower limit that must be exceeded to conclude that the visual function metrics are not deteriorating. system.

2. The system according to claim 1, wherein the light from the visual display is projected through a pupil with a diameter of approximately 3 mm, providing a numerical aperture sufficient to transmit high spatial frequency stimuli.

3. The system according to claim 1, wherein the retinal image is collected using an imaging device that illuminates the retina by scanning illumination across the retina or by projecting a series of illumination areas onto the retina, and synchronously detects light from the retina.

4. The system according to claim 3, wherein the imaging device provides confocal imaging, and alternatively, provides multiple scattered light imaging in which the illumination beam and the detection readout are spatially or temporally displaced.

5. The system according to claim 1, wherein the processor analyzes an image having a detection offset with respect to illumination in two or more directions within the image or over time.

6. The system according to claim 1, wherein the processor analyzes images of different illumination wavelengths, including NIR or visible illumination.

7. The system according to claim 1, wherein the processor collectively analyzes characteristics of the retinal image other than the intensity of the light returning from the eyeball, such as fluorescence, coherence, polarization, or changes over time in at least a video-rate image sequence, either at each location or over a wider area.

8. The system according to claim 1, wherein the wavefront measuring device for measuring the wavefront is a Shack-Hartmann sensor system.

9. The system according to claim 1, wherein the wavefront measuring device for measuring the wavefront uses visible illumination or NIR illumination.

10. The system according to claim 1, wherein the wavefront measuring device for measuring the wavefront has sufficient resolution to enable the specification of aberrations affecting vision that are not limited to spherical and cylindrical surfaces, but is designed to be less expensive or have lower resolution than that required to control the adaptive optical system necessary for generating diffraction-limited imaging.

11. The wavefront measurement system for measuring the wavefront includes, but is not limited to, modulating illumination synchronized with a sensor to improve the signal-to-noise ratio, and is temporally modulated to reduce the light necessary for the measurement of wavefront aberration, according to claim 1.

12. The system according to claim 1, wherein the wavefront measuring system for measuring the wavefront has a separate illumination source from the visual display.

13. The system according to claim 1, wherein the wavefront measuring device for measuring the wavefront reports the wavefront aberration of a pupil of about 3 mm.

14. The system according to claim 1, wherein the wavefront measuring device for measuring the wavefront reports the wavefront aberration of a pupil of about 3 mm and reports the amount corrected for spherical aberration, cylindrical aberration, and other lower-order aberrations.

15. The system according to claim 1, wherein the wavefront measuring device for measuring the wavefront reports the wavefront aberration of a pupil of about 3 mm, and reports the amount corrected by the adaptive optical system for spherical aberration, cylindrical aberration, other lower-order aberrations, and higher-order aberrations.

16. The system according to claim 1, wherein the wavefront measuring device for measuring the wavefront reports the wavefront aberration of a pupil of about 3 mm, and reports the amount of correction by the adaptive optical system for spherical aberration, cylindrical aberration, other lower-order aberrations, and higher-order aberrations in relation to clinical data or other data relating to the health of the anterior segment of the eye, such as the tear film and the lens.

17. The system according to claim 1, wherein the wavefront measuring device for measuring the wavefront reports the wavefront aberration of a pupil of about 3 mm, and the processor quantifies the amount corrected by the adaptive optical system for spherical aberration, cylindrical aberration, other lower-order aberrations, and higher-order aberrations in relation to clinical data or other data relating to the health of the anterior segment of the eye, such as the tear film and the lens, and refines the central tendency and variability of the measured visual function.

18. The system according to claim 1, wherein the focus from the visual display to the retina is improved by an adaptive optical system, and the improvement is quantified by the measurement value of a wavefront measuring system that measures the wavefront.

19. The system according to claim 1, wherein the focus from the visual display to the retina is improved by an adaptive optical system, and the control parameters of the adaptive optical system are specified by auxiliary measurements.

20. The system according to claim 3, wherein the imaging device has a wide field of view of 8 to 60 degrees to enable eccentric fixation and determination of retinal landmarks.

21. The system according to claim 3, wherein the imaging device has an enlarged field of view with a field of view angle of less than 8 degrees.

22. The system according to claim 1, wherein the measured values ​​of the visual function include a database or model of the effect of the uncorrectable wavefront aberration on the visual function.

23. The system according to claim 1, wherein the illumination of the wavefront measuring system for measuring the wavefront is performed by the visual display.

24. The system according to claim 1, further comprising a database or model of the influence on the central trend and variability of visual function measurements when none of the input measurements are measured simultaneously in the same device, or alternative or auxiliary measurements are input and constrained to a set of detection offsets for illumination in the retinal image or over time, b, c, d, e, g, or h.

25. A method for measuring visual function while quantifying or minimizing factors that negatively affect vision but are unrelated to the condition of the retina, (a) Projecting light onto the retina through the pupil of the eyeball, and allowing most of the light to pass through the pupil, to accurately transmit visual stimuli including high spatial frequency or low contrast while eliminating individual differences, (b) Receiving a fundus image that includes details based on one or more states of the retinal structure, subretinal structure, or fixation point trajectory, (c) To provide the trajectory of the retinal target, which is known as the trajectory of a fixation point and is known in other fields as the eccentric field of view, by comparing the visual stimulus received from the visual display with the fundus image, (d) Measuring wavefront aberration to evaluate the deviation of the wavefront on the surface of the pupil of the eyeball for the light that reaches the retina at the position of the visual stimulus, (e) Determining the focal point of the retina in the optical system of the eyeball from the wavefront measurement values, (f) Correcting the wavefront error of the visual display in order to achieve better focusing of the visual stimulus on the retina, (g) Report corrected and uncorrectable wavefront aberrations to the operator and use this information to interpret visual function measurements, (h) Record the patient's judgment regarding the visual stimulus, (i) Controlling one or more parameters of the visual stimulus based on the patient's response or a predetermined sequence, (j) The parameters used in the visual display or final output are calculated according to the results of b, c, d, g, h, and i and a model of the measured visual function, including prior data, all working together to identify the visual function that a given eye can potentially reach, and the measurements are optimized to quantify factors that adversely affect vision that are independent of the state of the retina, and to generate central trend and variability metrics that describe the state and potential state of the retina, Includes, The visual function metrics include predicted values ​​for visual acuity in the event of successful retinal treatment or elimination of irrelevant factors such as lens opacity, the visual function metrics include a measure of central tendency and variability, identify an upper limit that must be exceeded to conclude that the retinal condition has improved, and include a lower limit that must be exceeded to conclude that the retinal condition has not worsened. method.

Images