Multi-luminance mobility test for the assessment of vision

Abstract

The present disclosure relates to methods and systems for evaluating vision in subjects, particularly those with low vision or visual impairments. Further provided herein are methods and systems that enable effective testing to monitor and evaluate changes in a subject's vision over time.

Description

WSGR Docket No. 62351-711.601MULTI-LUMINANCE MOBILITY TEST FOR THE ASSESSMENT OF VISIONCROSS-REFERENCE

[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 709,260, filed October 18, 2024, and U.S. Provisional Application No. 63 / 799,090, filed May 02, 2025, which applications are incorporated herein in their entirety.BACKGROUND

[0002] Patients suffering from degenerative retinal diseases (e.g., retinitis pigmentosa (RP) or Leber congenital amaurosis (LCA)) often lead to progressive vision loss, which profoundly impacts a patient's ability to perform routine tasks. Evaluating a patient’s vision (e.g., visual function and functional vision) using standard visual tests falls short of capturing the full scope and severity of the patient’s visual impairments. There is a need for improved methods and systems to assess patients’ vision.BRIEF SUMMARY

[0003] Many traditional vision tests (e.g., tests to assess a patient’s visual function or functional vision), such as visual acuity or field tests, focus on specific aspects of vision but fail to fully capture how subjects with visual impairments or low vision navigate through everyday environments with fluctuating light levels, such as moving from bright sunlight to a dimly lit room. Such limitations can frustrate the measurement to evaluate changes or improvements of the subject’s vision, in particularly for a subject (e.g., a patient) with impaired vision or low vision, and restrain the testing and approval of medical interventions intended to treat the cause of such low vision.

[0004] Provided herein are methods and systems for overcoming the above mentioned limitations by evaluating the subject’s vision or monitoring changes in a subject’s vision by testing the subject to navigate through controlled environments with varying levels of complexity such as lighting conditions. For example, in some embodiments, factors such as depth perception, contrast sensitivity, or spatial awareness are measured to provide a comprehensive understanding of a patient’s visual function.

[0005] In one aspect, this disclosure provides a method for evaluating vision of a subject, the method comprising: (a) conducting a wayfinding test by presenting a first way finding course to the subject, wherein the first way finding course comprises: a darkcolored surface, a series of light colored markings on the dark surface forming a pathWSGR Docket No. 62351-711.601 demarcated by two parallel lines spaced from about 40 to about 60 centimeters (cm) apart from each other and a total length of the path is from about 6 to about 8 meters, wherein the path has a starting point, at least one turn, and an ending point to guide a subject through the dark surface; (b) selecting a first illumination level from a plurality of illumination levels; (c) illuminating the dark-colored surface; (d) recording movements of the subject from the starting point to the ending point; and (e) determining the vision of the subject. In some embodiments, the dark-colored surface has a length of from about 2 meters (m) to about 4 m, and a width of from about 3 m to about 7 m. In some embodiments, the dark-colored surface has a length of about 3 m and a width of about 5.5 m. In some embodiments, a width of each line of the two parallel lines is at least about 6 cm, at least about 8 cm, at least about 10 cm, at least about 12 cm, at least about 12.5 cm, at least about 13 cm, at least about 13.5 cm or at least about 14 cm. In some embodiments, a width of each line of the two parallel lines is about 12.5 cm. In some embodiments, a distance between the two parallel lines is about 50 cm. In some embodiments, the two parallel lines demarcating the path on the dark -colored surface have a color that exhibits at least about 25%, at least about 50%, at least about 75%, at least about 80%, at least about 90%, or 100% contrast level to the dark-colored surface. In some embodiments, the dark-colored surface is a black-colored surface or a graycolored surface. In some embodiments, the two parallel lines on the dark-colored surface are white-colored lines. In some embodiments, at least one turn comprises at least one 90-degree right or left turn. In some embodiments, the first wayfinding course has at least one turn, at least two turns, at least three turns, at least four turns, at least five turns, or at least six turns. In some embodiments, the first wayfinding course has four turns. In some embodiments, the plurality of illumination levels comprises at least 7 illumination levels, at least 8 illumination levels, at least 9 illumination levels, at least 10 illumination levels, at least 11 illumination levels, at least 12 illumination levels or more. In some embodiments, the plurality of illumination levels comprises 9 illumination levels. In some embodiments, the plurality of illumination levels range from about 0.1 lux to about 1000 lux. In some embodiments, each illumination of the plurality of illumination levels is spaced from an adjacent illumination level by about 0.5 log units. In some embodiments, the plurality of illumination levels comprise about 0.1, about 0.32, about 1.0, about 3.2, about 10.0, about 32, about 100, about 320, and about 1000 lux. In some embodiments, the first wayfinding course further comprises at least one obstacle. In some embodiments, the first wayfinding course has no obstacle. In someWSGR Docket No. 62351-711.601 embodiments, the determining the vision of the subject comprises determining time to complete the first wayfinding course. In some embodiments, the determining the vision of the subject comprises recording at least one failure criterion. In some embodiments, the at least one failure criterion comprises touching or extending beyond either one of the two parallel lines, taking longer than a predetermined time limit, or declaring inability to proceed with the wayfinding test. In some embodiments, the predetermined time limit is three times a duration required to navigate from the starting point to the ending point obtained during a practice wayfinding test. In some embodiments, the determining the vision of the subject comprises determining a first passing threshold illumination level. In some embodiments, the first passing threshold illumination level is a lowest illumination level that the subject successfully navigates from the starting point to the ending point of the wayfinding test. In some embodiments, the first passing threshold illumination level is determined after the subject successfully navigates from the starting point to the ending point of the wayfinding test for at least one trial, at least two trials, at least three trials, at least four trials, or at least five trials.

[0006] In some embodiments, the method further comprises: (a) conducting a follow-up wayfinding test by presenting a second wayfinding course to the subject; (b) selecting a second illumination level from the plurality of illumination levels; (c) illuminating the dark-colored surface; (d) recording movements of the subject; and (e) determining the vision of the subject. In some embodiments, the first wayfinding course and the second wayfinding course are the same. In some embodiments, the first wayfinding course and the second wayfinding course are different. In some embodiments, the first illumination level and the second illumination level are the same. In some embodiments, the first illumination level and the second illumination level are different. In some embodiments, the determining the vision of the subject of the follow-up wayfinding test comprises determining a second passing threshold illumination level. In some embodiments, the second passing threshold illumination level comprises a lowest illumination level that the subject successfully navigates from the starting point to the ending point of the follow-up wayfinding test. In some embodiments, duration between the wayfinding test and the follow-up wayfinding test is at least about 1 -month, at least about 2-month, at least about 3 -month, at least about 4-month, at least about 5 -month, at least about 6- month, at least about 7-month, at least about 8-month, at least about 9-month, at least about 10-month, at least about 11 -month, or at least about 12-month apart.WSGR Docket No. 62351-711.601

[0007] In some embodiments, the method further comprises: comparing the vision assessed at the wayfinding test and the visional function assessed at the follow-up wayfinding test to determine changes or improvement. In some embodiments, an improvement in the vision is achieved when the first passing threshold illumination level and the second passing threshold illumination level are different by at least two light levels, at least three light levels, at least four light levels, at least five light levels, at least six light levels, at least seven light levels, or at least eight light levels.

[0008] In some embodiments, the subject is a subject with profoundly impaired vision or low vision. In some embodiments, the subject with profoundly impaired vision or low vision has a visual acuity that is less than about 20 / 200, less than about 20 / 400, less than about 20 / 600, less than about 20 / 800, less than about 20 / 1000, less than about 20 / 2000, less than about 20 / 3000 or less best-corrected visual acuity (BCVA). In some embodiments, the subject has greater than about 1.0 logMAR BCVA, greater than about 1.2 logMAR BCVA greater than about 1.4 logMAR BCVA, greater than about 1.5 logMAR BCVA, greater than about 1.6 logMAR BCVA, greater than about 1.7 logMAR BCVA, greater than about 1.8 logMAR BCVA, 1.90 logMAR BCVA, or more. In some embodiments, the subject has less than about 10 degrees, less than about 8 degrees, less than about 6 degrees, less than about 5 degrees, less than about 4 degrees, less than about 3 degrees, or less than about 2 degrees in diameter of visual field. In some embodiments, the subject is suspected of having or having vision impairment or deficiency in one or both eyes. In some embodiments, the subject is a candidate for local or systemic ophthalmic treatment. In some embodiments, the local or systemic ophthalmic treatment is an ocular therapy, a surgery, a gene therapy, or a combination thereof. In some embodiments, the subject has an ocular disease. In some embodiments, the ocular disease is selected from the group consisting of retinitis pigmentosa (RP), Leber’s congenital amaurosis (LCA), Stargardt disease, Usher’s syndrome, choroideremia, a rod-cone or cone-rod dystrophy, a ciliopathy, a mitochondrial disorder, progressive retinal atrophy, a degenerative retinal disease, age related macular degeneration (AMD), wet AMD, dry AMD, geographic atrophy, a familial or acquired maculopathy, a retinal photoreceptor disease, a retinal pigment epithelial-based disease, diabetic retinopathy, cystoid macular edema, uveitis, retinal detachment, traumatic retinal injury, iatrogenic retinal injury, macular holes, macular telangiectasia, a ganglion cell disease, an optic nerve cell disease, glaucoma, optic neuropathy, ischemic retinal disease, retinopathy ofWSGR Docket No. 62351-711.601 prematurity, retinal vascular occlusion, familial macroaneurysm, a retinal vascular disease, an ocular vascular diseases, a vascular disease, and ischemic optic neuropathy. In some embodiments, prior to the wayfinding test or the follow-up wayfinding test, the subject is treated with an ocular therapy, an ocular surgery, and / or a gene therapy. In some embodiments, after the wayfinding test and prior to the follow-up wayfinding test, the subject is treated with an ocular therapy, a surgery, and / or a gene therapy. In some embodiments, the evaluating vision comprises evaluating a functional vision of the subject or evaluating a visual function of the subject.

[0009] In another aspect, this disclosure provides a method of monitoring vision of a subject that has received at least one ophthalmic treatment, the method comprising: (a) determining a first passing threshold illumination level of the subject using the method of any one of claims 1-48 at a first time point; (b) determining a second passing threshold illumination level of the subject using the method of any one of claims 1 -48 at a second time point; and (c) determining effectiveness of the at least one ophthalmic treatment by comparing the first passing threshold illumination level and the second passing threshold illumination level. In some embodiments, the at least one ophthalmic treatment is an ocular therapy, a surgery, a gene therapy, or a combination thereof. In some embodiments, the ocular therapy, surgery, or the gene therapy is for treatment of retinitis pigmentosa (RP), Leber’s congenital amaurosis (LCA), Stargardt disease, Usher’s syndrome, choroideremia, a rod-cone or cone-rod dystrophy, a ciliopathy, a mitochondrial disorder, progressive retinal atrophy, a degenerative retinal disease, age related macular degeneration (AMD), wet AMD, dry AMD, geographic atrophy, a familial or acquired maculopathy, a retinal photoreceptor disease, a retinal pigment epithelial -based disease, diabetic retinopathy, cystoid macular edema, uveitis, retinal detachment, traumatic retinal injury, iatrogenic retinal injury, macular holes, macular telangiectasia, a ganglion cell disease, an optic nerve cell disease, glaucoma, optic neuropathy, ischemic retinal disease, retinopathy of prematurity, retinal vascular occlusion, familial macroaneurysm, a retinal vascular disease, an ocular vascular diseases, a vascular disease, or ischemic optic neuropathy. In some embodiments, the first time point and the second time point is at least about 1 -month, at least about 2- month, at least about 3 -month, at least about 4-month, at least about 5 -month, at least about 6-month, at least about 7-month, at least about 8-month, at least about 9-month, at least about 10-month, at least about 11 -month, or at least about 12-month apart fromWSGR Docket No. 62351-711.601 each other. In some embodiments, the subject receives the at least one ophthalmic treatment before the first time point. In some embodiments, the subject receives the at least one ophthalmic treatment after the first time point and before the second time point. In some embodiments, the subject receives the at least one ophthalmic treatment after the second time point.

[0010] In some embodiments, the method further comprises: monitoring the progress of the subject that is undergoing or has received the at least one ophthalmic treatment; and determining effectiveness of the at least one ophthalmic treatment. In some embodiments, the at least one ophthalmic treatment is determined to be effective when the first passing threshold illumination level and the second passing threshold illumination level are different by at least two light levels, at least three light levels, at least four light levels, at least five light levels, at least six light levels, at least seven light levels, or at least eight light levels.

[0011] In another aspect, this disclosure provides a wayfinding system comprising: (a) a dark surface; (b) a series of light colored markings on the dark surface forming a path demarcated by two parallel lines spaced at least about 40-60 centimeters (cm) apart and the path has a total length of about 6-8 meters, wherein the path has a starting point, at least one turn, and an ending point to guide a subject through the dark surface; (c) a light system configured to provide adjustable illumination levels; and (d) a detection system configured to monitor movements of the subject from the starting point to the ending point. In some embodiments, the dark-colored surface has a length of from about 2 meters (m) to about 4 m, and a width of from about 3 m to about 7 m. In some embodiments, the dark-colored surface has a length of about 3 m and a width of about5.5 m. In some embodiments, a width of each line of the two parallel lines is at least about 6 cm, at least about 8 cm, at least about 10 cm, at least about 12 cm, at least about12.5 cm, at least about 13 cm, at least about 13.5 cm or at least about 14 cm. In some embodiments, a width of each line of the two parallel lines is about 12.5 cm. In some embodiments, a distance between the two parallel lines is about 50 cm. In some embodiments, the two parallel lines demarcating the path on the dark -colored surface have a color that exhibits at least about 25%, at least about 50%, at least about 75%, at least about 80%, at least about 90%, or 100% contrast level to the dark-colored surface. In some embodiments, the dark-colored surface is a black-colored surface or a graycolored surface. In some embodiments, the two parallel lines on the dark-colored surfaceWSGR Docket No. 62351-711.601 are white-colored lines. In some embodiments, at least one turn comprises at least one 90-degree right or left turn. In some embodiments, the wayfinding course has at least one turn, at least two turns, at least three turns, at least four turns, at least five turns, or at least six turns. In some embodiments, the wayfinding course has four turns. In some embodiments, the light system comprises a plurality of light. In some embodiments, the plurality of light comprises light-emitting diodes. In some embodiments, each of the plurality of light is configured to provide a plurality of illumination levels comprising at least 7 illumination levels, at least 8 illumination levels, at least 9 illumination levels, at least 10 illumination levels, at least 11 illumination levels, at least 12 illumination levels or more. In some embodiments, the plurality of illumination levels comprises 9 illumination levels. In some embodiments, the plurality of illumination levels range from about 0.1 lux to about 1000 lux. In some embodiments, each illumination of the plurality of illumination levels is spaced from an adjacent illumination level by about 0.5 log units. In some embodiments, the plurality of illumination levels comprise about 0.1, about 0.32, about 1.0, about 3.2, about 10.0, about 32, about 100, about 320, and about 1000 lux. In some embodiments, the wayfinding course further comprises at least one obstacle. In some embodiments, the wayfinding course has no obstacle. In some embodiments, the detecting system comprises a video-recording device configured to record a movement of the subject. In some embodiments, the system is for evaluating vision of the subject. In some embodiments, the subject is a subject with profoundly impaired vision or low vision. In some embodiments, the subject with profoundly impaired vision or low vision has a visual acuity that is less than about 20 / 200, less than about 20 / 400, less than about 20 / 600, less than about 20 / 800, less than about 20 / 1000, less than about 20 / 2000, less than about 20 / 3000 or less best-corrected visual acuity (BCVA). In some embodiments, the subject has greater than about 1.0 logMAR BCVA, greater than about 1.2 logMAR BCVA greater than about 1.4 logMAR BCVA, greater than about 1.5 logMAR BCVA, greater than about 1.6 logMAR BCVA, greater than about 1.7 logMAR BCVA, greater than about 1.8 logMAR BCVA, 1.90 logMAR BCVA, or more. In some embodiments, the subject has less than about 10 degrees, less than about 8 degrees, less than about 6 degrees, less than about 5 degrees, less than about 4 degrees, less than about 3 degrees, or less than about 2 degrees in diameter of visual field.WSGR Docket No. 62351-711.601

[0012] Additional aspects and advantages of the present disclosure will become readily apparent to those skilled in this art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the disclosure. Accordingly, the drawings and description are to be regarded as illustrative in nature, and not as restrictive.INCORPORATION BY REFERENCE

[0013] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.BRIEF DESCRIPTION OF THE FIGURES

[0014] Various features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which principles of the invention are utilized, and the accompanying drawings of which:

[0015] FIG. 1 shows exemplary way finding courses. Each way finding course is constructed in a dark surface sheet (3 meters (m) by 4.5 m) and a series of markings forming a path (a total length of 7 m) demarcated by two parallel lines spaced about 50 centimeters (cm) apart, where each line of the two parallel lines is about 12.7 cm wide.

[0016] FIG. 2A shows a testing room set-up with lighting and an exemplary wayfinding course with high contrast. FIG. 2B depicts a computer panel that controls the lighting (e.g., illumination levels).

[0017] FIG. 3 illustrates example data showing correlation between visual acuity (LogMAR) on ETDRS and wayfinding MLMT (MLMTw) score on visit 1 .

[0018] FIG. 4 illustrates example data showing correlation between grating contrast sensitivity (CS) value measured with area under the curve of logCS values and MLMTw scores.WSGR Docket No. 62351-711.601

[0019] FIG. 5 illustrates example data showing correlation between MLMTw score and approximate diameter of central visual field in degrees.DETAILED DESCRIPTIONDefinitions

[0020] Unless defined otherwise, all terms of art, notations and other technical and scientific terms or terminology used herein are intended to have the same meaning as is commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and / or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art.

[0021] In the description and the following claims, the following will be appreciated. The phrases “at least one,” “one or more,” and “and / or,” as used herein, are open-ended expressions that are both conjunctive and disjunctive in operation. The terms “a,” “an,” “the,” “first,” “second,” etc., do not preclude a plurality. For example, the term “a” or “an” entity, as used herein, refers to one or more of that entity. As such, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein.

[0022] Unless otherwise specified, the term “about” when used before a numerical designation, e.g., time, amount, size, should be understood to include variations of ±10% around the stated value. In case of illumination level, the term “about” should be understood to include variation of ±0.5 log.

[0023] The term “comprises / comprising” does not exclude the presence of other elements, components, features, regions, integers, steps, operations, etc. By contrast, the transitional phrase “consisting of’ excludes any element, step, or ingredient not specified in the claim. The transitional phrase “consisting essentially of’ limits the scope of a claim to the specified materials or steps “and those that do not materially affect the basic and novel characteristic(s)” of the claimed invention.

[0024] The term “visual function” refers to the physiological capability of the visual system of an individual to process and respond to light stimuli, enabling the perception of visual information. It encompasses various aspects such as visual acuity, contrast sensitivity, depth perception, color vision, and the ability to detect motion. VisualWSGR Docket No. 62351-711.601 function is often assessed through clinical tests to determine the health and performance of the eye and visual pathways.

[0025] The term “functional vision” refers to how effectively an individual (e.g., a subject or a patient) uses his or her visual abilities to perform daily activities in a specified setting. The assessment typically includes practical, task-oriented visual performance, such as the ability to navigate, recognize objects, read, or interact with the environment under various lighting conditions.

[0026] The term “visual field” refers to the total area in which objects can be seen in the peripheral vision while the eye is focused on a central point. It is the extent of the observable environment seen at any given moment, encompassing both central and peripheral vision. The visual field is often measured in degrees, with specific tests assessing any deficits or scotomas (blind spots) that may limit the field of vision.

[0027] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.Overview

[0028] Provided herein are methods and systems to evaluate vision of a subject. In some embodiments, the subject described herein can be a subject with impaired vision or low vision. In some embodiments, the methods and systems described herein may comprise (1) a wayfinding course (also referred as wayfinding MLMT or MLMTw) configured to evaluate a subject’s vision (e.g., functional vision); (2) a plurality of lights configured to control illumination levels; and (3) a video-recording device configured to record a movement of the subject as the subject walks or otherwise navigates on the way finding course.

[0029] In some embodiments, the methods and systems described herein can integrate visual field (VF), visual acuity (VA), and light sensitivity. In some embodiments, the mobility performance tasks described herein (e.g., a wayfinding test) can integrate VF, VA, and light sensitivity into quantitative measures and / or qualitative measures. In some embodiments, the mobility performance tasks described herein (e.g., a wayfinding test) can integrate VF, VA, and light sensitivity into quantitative measures and / or qualitative measures to monitor changes in a subject’s vision (e.g., functional vision) for a period of time (e.g., from one week to one year). This feature is particularly important for evaluating or monitoring vision of subjects with visual impairment or low vision, as theyWSGR Docket No. 62351-711.601 may have varying degrees of visual function and functional vision. For example, a subject with visual impairment (e.g., low vision) may have normal vision as measured by visual acuity (e.g., visual acuity greater than 20 / 100) on an eye chart, but still have significant difficulty performing everyday tasks that require an assistance due to issues such as poor peripheral vision, difficulty with contrast sensitivity, or problems with eye movement coordination.

[0030] Further provided herein are methods and systems to monitor vision of a subject. In some embodiments, the methods and systems described herein comprise monitoring vision of a subject, wherein the subject has received at least one ophthalmic treatment (e.g., an ocular therapy, a surgery, or a gene therapy). In some embodiments, the methods and systems described herein comprise monitoring vision of a subject, wherein the subject has ocular diseases. In some embodiments, the methods and systems described herein can enable effective testing for monitoring and evaluating changes in a subject’s vision over time. For example, the testing (e.g., performing the wayfinding test described herein) can be conducted at two or more distinct timepoints to track and evaluate progression or changes in a subject’s vision. Results from the initial test (e.g., an initial evaluation test) may serve as a baseline, while the follow-up tests (e.g., one or more follow-up evaluation tests) allow for comparative analysis to assess changes or trends over time. The ability to perform both initial and follow-up tests (e.g., one or more follow-up tests) to assess a subject’s vision (e.g., of a subject with low vision) is a significant improvement over conventional / traditional assessments as the results obtained using the conventional / traditional assessments cannot be performed reliably, even at the highest luminance level for patients with low vision. For example, the conventional / traditional assessment can only be completed by patients with better vision (e.g., patients with higher than 20 / 200 visual acuity) as the task requires individuals to gather environmental information, recognize their current location, establish a path to their destination, and ensure safe walking, avoiding collisions with obstacles and other pedestrians. Individuals with normal vision depend on their wide field of view and clear visual acuity for seamless navigation. In contrast, patients with low vision face challenges and experience elevated cognitive workload when performing a wayfinding task owing to their restricted visual function, and ultimately cannot complete the test. The methods and systems described herein overcome this limitation by developing a more simplified wayfinding test compared to the conventional / traditional assessment,WSGR Docket No. 62351-711.601 such that the test may be better suited for a subject with low vision or vision impairment. For example, the methods and systems described herein provide defined parameters, such as path length or width, which enable patients with low vision or visual impairments to follow a path marked by two lines of the wayfinding test. These systems also allow for the establishment of a baseline threshold and ensure that these tests are both precise and repeatable.

[0031] Provided herein are methods and systems for evaluating vision, visual performance (or changes thereof) of a subject. In some embodiments, the subject has low vision or impaired vision. In some embodiments, evaluating vision (or changes thereof) can be evaluating functional vision or visual function of a subject. In some embodiments, evaluating vision of a subject can comprise conducting a wayfinding test by presenting a wayfinding course to the subject and assessing the subject’s ability to navigate from a starting point to an ending point of the wayfinding course. In some embodiments, the method and system can further comprises selecting an illumination level from a plurality of illumination levels, recording movements of the subject from the starting point to the ending point, and determining the vision (e.g., functional vision) of the subject. In some embodiments, the methods and systems can further evaluate the vision (e.g., functional vision) of the subject based on one or more functional performances.Wayfmding course

[0032] The methods and systems described herein can evaluate the subject’s vision by assessing how the subject navigates the wayfinding test (e.g., by measuring metrics such as time taken to complete the path, number of errors, distance deviated from the path, speed of navigation, etc.). The wayfinding course described herein may comprise a darkcolored surface and a series of markings on the dark surface forming a path demarcated by two parallel lines. In some embodiments, the path demarcated by two parallel lines has a starting point and an ending (e.g., finishing) point. In some embodiments, the length of the dark-colored surface may be at least about 2 m, at least about 3 m, at least about 4 m, at least about 5 m, at least about 6 m, at least about 7 m, at least about 8 m, at least about 9 m, at least about 10 m. In some embodiments, the width of the dark -colored surface can be at least about 2 m, at least about 3 m, at least about 4 m, at least about 5 m, at least about 6 m, at least about 7 m, at least about 8 m, at least about 9 m, at least about 10 m. In some embodiments, the dark-colored surface may have a length of from about 2 meters (m) to about 10 m, and a width of from about 2 m to about 10 m. ForWSGR Docket No. 62351-711.601 example, in some embodiments, the dark -colored surface may have a length of about 3 m and a width of about 5 m.

[0033] The path on the dark-colored surface can be demarcated by two parallel lines with a starting point and an ending point (e.g., a finishing point). In some embodiments, a total length of the path (e.g., measured from a starting point to the ending point) can be at least about 5 meters (m), at least about 6 m, at least about 7 m, at least about 8 m, at least about 9 m, or at least about 10 m. In some embodiments, the total length of the path can be about 5 m, about 6 m, about 7 m, about 8 m, about 9 m, or about 10 m. In some embodiments, the total length of the path (e.g., measured from the starting point to the ending point) can be measured along the centerline of the two parallel lines (e.g., an average path length).

[0034] In some embodiments, the two parallel lines can be at least about 40 centimeters (cm) apart, at least about 50 cm apart, at least about 60 cm apart, at least about 70 cm apart, at least about 80 cm apart, at least about 90 cm apart, or at least about 100 cm apart (e.g., the distance between two parallel lines). For example, in some embodiments, the distance between two parallel lines can be about 40 cm, about 50 cm, about 60 cm, about 70 cm, about 80 cm, about 90 cm, or about 100 cm. The distance between the two parallel lines can be measured from the centerline (e.g., mid-point) of each line of the two parallel lines.

[0035] In some embodiments, a width of each line of the two parallel lines can be at least about 5 cm, at least about 6 cm, at least about 7 cm, at least about 8 cm, at least about 9 cm, at least about 10 cm, at least about 11 cm, at least about 12 cm, at least about 12.5 cm, at least about 13 cm, at least about 13.5 cm, at least about 14 cm, or at least about 15 cm. For example, in some embodiments, the width of each line of the two parallel lines can be about 10 cm, about 11 cm, about 12 cm, about 12.5 cm, about 13 cm, about 14 cm, or about 15 cm. In some embodiments, the width of each line of the two parallel lines can be set to be the same as the widest stripe on the grating acuity test for a subject who is at the maximum measurable range of 20 / 8000 as measured from 1 meter. In some embodiments, the width of each line of the two parallel lines can be selected such that the final path can comprise patterns that have some variations to reduce memorization.

[0036] In some embodiments, the path of the wayfinding course can comprise 1 turn to 10 turns. In some embodiments, the path of the wayfinding course can comprise 1 turn toWSGR Docket No. 62351-711.6012 turns, 1 turn to 3 turns, 1 turn to 4 turns, 1 turn to 5 turns, 1 turn to 6 turns, 1 turn to 7 turns, 1 turn to 8 turns, 1 turn to 9 turns, 1 turn to 10 turns, 2 turns to 3 turns, 2 turns to 4 turns, 2 turns to 5 turns, 2 turns to 6 turns, 2 turns to 7 turns, 2 turns to 8 turns, 2 turns to9 turns, 2 turns to 10 turns, 3 turns to 4 turns, 3 turns to 5 turns, 3 turns to 6 turns, 3 turns to 7 turns, 3 turns to 8 turns, 3 turns to 9 turns, 3 turns to 10 turns, 4 turns to 5 turns, 4 turns to 6 turns, 4 turns to 7 turns, 4 turns to 8 turns, 4 turns to 9 turns, 4 turns to10 turns, 5 turns to 6 turns, 5 turns to 7 turns, 5 turns to 8 turns, 5 turns to 9 turns, 5 turns to 10 turns, 6 turns to 7 turns, 6 turns to 8 turns, 6 turns to 9 turns, 6 turns to 10 turns, 7 turns to 8 turns, 7 turns to 9 turns, 7 turns to 10 turns, 8 turns to 9 turns, 8 turns to 10 turns, or 9 turns to 10 turns. In some embodiments, the path of the wayfinding course can comprise 1 turn , 2 turns, 3 turns, 4 turns, 5 turns, 6 turns, 7 turns, 8 turns, 9 turns, or 10 turns. In some embodiments, the path of the wayfinding course can comprise at least 1 turn, 2 turns, 3 turns, 4 turns, 5 turns, 6 turns, 7 turns, 8 turns, or 9 turns. In some embodiments, the path of the wayfinding course can comprise at most 2 turns, 3 turns, 4 turns, 5 turns, 6 turns, 7 turns, 8 turns, 9 turns, or 10 turns. In some embodiments, the path of the wayfinding course has exactly 4 turns.

[0037] In some embodiments, a turn (e.g., at least one turn of the plurality of turns) of the wayfinding course can be a 90 degree turn, a 85 degree turn, a 80 degree turn, a 75 degree turn, a 70 degree turn, a 65 degree turn, a 60 degree turn, a 55 degree turn, a 50 degree turn, or less.A Plurality of Light-Illumination levels

[0038] The methods and systems described herein can evaluate a subject’s vision by assessing how the subject navigates the wayfinding test (e.g., by metrics such as time taken to complete the path, number of errors, distance deviated from the path, speed of navigation, etc.) under specific or varying illumination levels. In some embodiments, the methods and systems described herein can comprise a plurality of lights configured to control the illumination levels.

[0039] In some embodiments, the plurality of lights can comprise light-emitting diodes (LEDs). For example, the plurality of lights can comprise at least five LED panel lights, at least six LED panel lights, at least seven LED panel lights, at least eight LED panel lights, at least nine LED panel lights, or at least ten LED panel lights. In some embodiments, the LED panel light can be a theater-type LED panel light.WSGR Docket No. 62351-711.601

[0040] In some embodiments, the illumination level can be controlled with LED panels providing indirect lights (e.g., by LED panels directed at the ceiling for indirect reflection that eliminates shadows). In some embodiments, the illumination level can be controlled with LED panels providing direct lights (e.g., by LED panels directed at the wayfinding course and the subject). Each panel can be programmed for consistent color and brightness using a computer program. In some embodiments, the plurality of lights can be spaced around the edge of the course to create uniform illumination. In some embodiments, the plurality of lights is interfaced with a computer, and each light level (each illumination level) comprising an evenly distributed color, temperature, and illumination that is programmed with an established preset setting.

[0041] In some embodiments, each light of the plurality of lights can provide (e.g., capable of emitting) one or more illumination levels. In some embodiments, the light of the plurality of lights can be configured such that the light can provide at least 5 illumination levels, at least 6 illumination levels, at least 7 illumination levels, at least 8 illumination levels, at least 9 illumination levels, at least 10 illumination levels, at least 11 illumination levels, at least 12 illumination levels or more. In some embodiments, one or more illumination levels can range from about 0.1 lux to about 1000 lux. In some embodiments, each illumination can be spaced from an adjacent illumination level by about 0.2 log units, about 0.3 log units, about 0.4 log units, about 0.5 log units, about 0.6 log units, about 0.7 log units, about 0.8 log units, about 0.9 log units, or about 1.0 log units (e.g., increments of 0.5 log steps higher or lower than the previous setting). For example, the light can provide about 0.1, about 0.32, about 1.0, about 3.2, about 10.0, about 32, about 100, about 320, and about 1000 lux illumination levels. In some embodiments, the methods and systems described herein may further comprise a light meter configured to measure illumination level.Contrast levels

[0042] The methods and systems described herein can evaluate a subject’s vision by assessing how the subject navigates the wayfinding test (e.g., by measuring metrics such as time taken to complete the path, number of errors, distance deviated from the path, speed of navigation, etc.) under specific or varying illumination levels and / or contrast level. The term “contrast level” as used herein refers to the difference in visual intensity between two objects (e.g., between the dark surface and the parallel lines forming the path). For example, in some embodiments, the contrast level can be defined as the degreeWSGR Docket No. 62351-711.601 of distinction between the color or brightness of the two objects, making it easier or harder to visually distinguish one from the other. A higher contrast level (e.g., 100% contrast level) may indicate a strong difference between the two objects, making it easier to distinguish one from the other. A lower contrast level (e.g., 0% contrast level) may indicate less or no difference between the two objects, making it harder to distinguish one from the other.

[0043] In some embodiments, the contrast level can be described using percent contrast level. In some embodiments, the contrast level between the dark surface and the parallel lines forming the path can be at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or 100%. In some embodiments, the percent (%) contrast level can be calculated using the formulation: [(L1-L2) / (L1+L2)]* 100, where LI is the relative luminance of the lighter color, and L2 is the relative luminance of the darker color. For example, when the contrast level between the dark surface and the parallel lines forming the path is 100%, the dark-colored surface can be a black-colored surface, while the two parallel lines on the dark-colored surface can be white-colored lines. In some embodiments, the dark colored surface can be a dark gray-colored surface, while the two parallel lines on the dark-colored surface can be white-colored lines. In some embodiments, the contrast level can be described using contrast ratios. The contrast ratios can be calculated using the formula: (LI + 0.05) / (L2 + 0.05), where LI is the relative luminance of the lighter color, and L2 is the relative luminance of the darker color. For example, in some embodiments, a contrast level of 1 :1 indicates no contrast, and 21 :1 indicates maximum contrast. In some embodiments, the contrast ratio between the dark surface and the parallel lines forming the path can be 1 :1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11 :1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, or 21 :1.

[0044] In some embodiments, the dark surface can be a dark gray surface with white parallel lines. In some embodiments, the dark surface can be a black surface with white parallel lines.

[0045] In some embodiments, the contrast level between the dark surface and the parallel lines can be changed depending on the visual acuity of the subject. For example, for a subject in a range near 20 / 200 and / or who has visual fields with larger diameter orWSGR Docket No. 62351-711.601 an inferior spared island of vision (e.g., greater than 10% visual field), the contrast level between the dark surface and the parallel lines forming the path can be lowered (e.g., contrast level of about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%). In some embodiments, the dark surface can be a light gray surface with white parallel lines.

[0046] In some embodiments, for subject in a range near 20 / 200 and / or who has visual fields with larger diameter or an inferior spared island of vision (e.g., greater than 10% visual field), the contrast ratio between the dark surface and the parallel lines forming the path can be lowered (e.g., contrast ratio of 2: 1, 3 : 1 , 4: 1 , 5 : 1 , 6: 1 , 7:1, 8:1, 9:1, 10:1, 11 :1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1).

[0047] In some embodiments, the use of, for example, the high contrast level or the low contrast level can be determined for each study subject. In some embodiments, the contrast level for each study subject is determined at the initial visit (e.g., at the preparation / practice round). In some embodiments, the contrast level can be changed for each study subject per each visit (e.g., at an initial vision, a second visit, a third visit etc.). In some embodiments, the contrast level can remain the same for each study subject throughout the entire period of the study (e.g., all following study visits throughout the study).Obstacles

[0048] In some embodiments, the methods and system described here may comprise a wayfinding course comprising no obstacle. In some embodiments, the methods and system described here may comprise a wayfinding course comprising one or more obstacles. For example, in some embodiments, the wayfinding course can comprise no obstacle, at least one obstacle, at least two obstacles, at least three obstacles, at least four obstacles, at least five obstacles, at least six obstacles, at least seven obstacles, at least eight obstacles, at least nine obstacles, or at least ten obstacles. In some embodiments, an obstacle can be selected from: an object placed in the path and an object placed adjacent to the path. In some embodiments, an obstacle may vary in size. In some embodiments, an obstacle may vary in contrast level (e.g., against the dark surface or the two parallel lines).WSGR Docket No. 62351-711.601Data Capture

[0049] In some embodiments, the methods and system described herein can comprise a data capture system (e.g., video recording) configured to capture, track, record, and / or analyze the subject's movements from a starting point to an ending point of the wayfinding course. For example, in some embodiments, the data capture system may comprise, but are not limited to, video recording (e.g., a camera), motion sensors (e.g., infrared sensors, ultrasonic sensors, or accelerometers), tracking system (e.g., global positioning system (GPS), light detection and ragging (LIDAR) systems), wearable devices (e.g., smart bands, motion trackers, or other biometric monitoring devices), or a combination thereof. In some embodiments, the data capture system described herein can further comprise data logging and storage device configured to log and store the data obtained (e.g., obtained from video recording) in a digital format. In some embodiments, the data storage system can include cloud-based platforms, local servers, or databases that allow for secure storage, retrieval, and analysis of the recorded data. In some embodiments, the data captured by the system described herein can be analyzed by one or more graders to assess the subject’s movements and overall performance to evaluate the subject’s vision (e.g., visual function or functional vision). For example, the grader can assess (a) the time for the subject to complete the wayfinding course, (b) the number of major errors, and (c) success rate (e.g., completion of the test). For example, the major errors can include touching or extending beyond either one of the two parallel lines.Evaluating the patient’s vision

[0050] Described herein are methods and systems to evaluate and monitor a subject’s vision. In some embodiments, the methods and systems described herein can evaluate and monitor the subject’s vision by assessing the subject’s vision-related abilities. For example, the assessment of a subject’s vision-related abilities can include assessing visual function, functional vision, or both.

[0051] In some embodiments, the methods and systems described herein can have a preparation / practice round to determine the illumination level to be tested in the evaluation test. In some embodiments, the preparation / practice round can comprise (1) conducting a wayfinding test by presenting a wayfinding course, (2) selecting a high illumination level (e.g., 32, 100, 320, 1000 lux) such that the subject can be familiarized with the test, and (3) recording movements of the subject navigating from a starting point to an ending point of the wayfinding course. In some embodiments, if the subjectWSGR Docket No. 62351-711.601 can successfully navigate the way finding course, the illumination level can be lowered to a level that would result in an inability for the subject to complete the wayfinding test (e.g., a threshold level or a no-pass level).

[0052] In some embodiments, the methods further comprise allowing the subject to be dark adapted. In some embodiments, the dark adaptation may be applied to a subject that successfully navigated (or expected to successfully navigate) the wayfinding test with illumination level of 10.0 lux or lower. The dark adaptation can be carried out for at least about 5 minutes, at least about 10 minutes, at least about 15 minutes, at least about 20 minutes, at least about 25 minutes, at least about 30 minutes, or more. In some embodiments, the dark adaptation may not be needed for a subject lacking a functional rod. In some embodiments, lack of rod function can be confirmed with a full-field stimulus test (FST), which involves exposing the subject to light stimuli of varying intensities and measuring the ability to detect the light. In some embodiments, the dark adaptation may not be needed for a subject that failed to navigate the wayfinding course (or expected to fail) at an illumination level that is higher than 10.0 lux. In some embodiments, the preparation / practice round can be used to determine the threshold level (e.g., no pass level).

[0053] In some embodiments, an evaluation test can be conducted after the preparation / practice round or upon determination of the threshold level. The methods and systems described herein may comprise an evaluation test, wherein the subject’s vision is assessed by conducting a wayfinding test, presenting a wayfinding course (e.g., the wayfinding course that is different from the one used in the preparation / practice round), and selecting a first illumination level, wherein the first illumination level is predetermined based on the threshold level (e.g., obtained in the preparation / practice round). In some embodiments, the first illumination level for the evaluation test can be a light level that is at least one light level lower than the threshold level (e.g., no pass level), at least two light levels lower than the threshold level (e.g., no pass level), at least three light levels lower than the threshold level (e.g., no pass level), at least four light levels lower than the threshold level (e.g., no pass level), or at least five light levels lower than the threshold level (e.g., no pass level) determined at the preparation / practice round. In some embodiments, when the subject cannot complete the wayfinding test at a first illumination level (e.g., at least two light levels lower than the threshold level determined at the preparation / practice round), the illumination level can be increasedWSGR Docket No. 62351-711.601(e.g., increased by one light level, increased by two light levels, increased by three light levels, etc.) until the subject can successfully navigate the wayfinding course. In some embodiments, each illumination level is tested at least once, at least twice, or at least three times.

[0054] In some embodiments, the methods and systems described herein can comprise evaluating the subject’s vision based on pass or fail criteria. For example, in some embodiments, the failure criteria may comprise a condition that the subject cross over completely to the outside of either line of the parallel lines at any point (e.g., crossing over at least one foot completely to the outside of any one of the parallel lines. In some embodiments, the failure criteria may comprise a condition that the subject failed to complete a wayfinding course at least two times (e.g., of the two independent evaluation trials), at least three times, at least four times, at least five times, or more slower (e.g., time taken to complete the trial) than the time taken to complete the trail recorded at the end of the preparation / practice round. For example, if a subject takes 60 seconds to complete in the higher illumination level (e.g. , the illumination level determined at the preparation / practice round), 180 seconds (3 minutes) may be used as a no-pass threshold. In some embodiments, the failure condition may comprise when the subject displays extensive pause during the trial (e.g., at least 30 seconds, at least 60 seconds, at least 90 seconds or more). In some embodiments, the failure condition may comprise a condition where the subject walks out of the path. In some embodiments, video recordings can be sent off to one or more graders for their masked grading process. The graders will determine: (a) the time for the subject to complete each course, and / or (b) the number of major errors when the subject completes each course (e.g., success / fail criteria).

[0055] In some embodiments, the methods and systems described herein can comprise evaluating the subject’s performance during the wayfinding test based on illumination level. In some embodiments, the methods and system described herein can comprise evaluating the subject’s performance during the wayfinding test based on at least one performance factor (e.g., functional performance). For example, the performance factor can include, but is not limited to, navigation accuracy and path maintenance, locomotor control and movement dynamics, visual function, cognitive / behavior component, or temporal metrics. In some embodiments, the performance factor can evaluate or characterize a subject’s functional visual ability and navigational proficiency during the wayfinding test. In some embodiments, the performance factor may be used individuallyWSGR Docket No. 62351-711.601 or in combination to compute a composite performance score. In some embodiments, the composite performance score can be representative of the subject’s overall visual performance under defined luminance conditions.

[0056] In some cases, the systems and methods can evaluate the subject’s ability to maintain proper course alignment and follow a designated route. In some embodiments, metrics may include a frequency or magnitude of trajectory steadiness, path deviation, collision or near-collision count, or course completion success. For example, a score of the trajectory steadiness can be based on a frequency or magnitude of deviation from a path centerline of the wayfinding test. In some cases, the systems and methods can evaluate the subject’s physical coordination and movement stability. In some embodiments, metrics may include a frequency or magnitude of gait consistency, posture stability, head position control, or turning precision. For example, a score of the posture and head position can be based on a frequency of torso sway or head tilts. In some cases, the system and methods can evaluate visual and perceptual parameters that influence navigational performance. The metrics may include baseline illuminance threshold, contrast sensitivity performance, path completion or closure, or visual scanning efficiency. For example, a score of the path completion / closure can be based on an ability to visually or spatially complete the way finding test by the subject. In some cases, the systems and methods can analyze higher-order behavior patterns, such as decision making time, error recovery, learning or adaptation, or confidence or hesitation. For example, a score can be based on a frequency or magnitude of pauses that the subject has taken during a wayfinding test. In some cases, a number of pauses can be recorded when the pause is at least about 1 second, at least about 2 seconds, at least about 3 seconds, at least about 4 seconds, or at least about 5 seconds. In some cases, the systems and methods can further compute temporal indicators such as total course completion time.In some cases, the systems and methods can ignore temporal indicators (e.g., total course completion time).

[0057] In some cases, each performance factor can be assigned a score, for example, on a scale from 1 to 4, where a higher score corresponds to improved performance. The composite score may be determined by summing or otherwise combining the individual factor scores. In some embodiments, selected performance factor and or illumination level may contribute disproportionately (e.g., weighted) to the composite score. For example, the composite score may be determined by summing a score associated withWSGR Docket No. 62351-711.601 the illumination level (e.g., a score corresponding to a particular luminance condition) and one or more scores obtained from the functional performance factor. The score associated with the illumination level may be assigned increased influence (e.g., weighted), for example, by applying a multiplier of two, three, four, or more relative to the other scores.

[0058] Provided herein are methods and systems for evaluating vision of a subject with low vision or impaired vision, wherein the methods and system further comprise a follow-up evaluation test (e.g., a follow-up evaluation test). In some embodiments, the methods and systems may comprise (a) conducting a follow-up wayfinding test by presenting a second wayfinding course to the subject; (b) selecting a second illumination level from the plurality of illumination levels; (c) recording movements of the subject; and (d) determining the visual function of the subject.

[0059] In some embodiments, the follow-up evaluation test can be conducted to monitor the subject’s vision over time. For example, the testing (e.g., wayfinding tests) can be conducted at two or more distinct timepoints to track and evaluate progression. Results from the initial test (e.g., the evaluation test) may serve as a baseline, while the follow-up tests (e.g., the follow-up evaluation test) allow for comparative analysis to assess changes or trends over time.

[0060] In some embodiments, when the first illumination level of the evaluation test and the second illumination level are different by at least one light level, at least two light levels, at least three light levels, at least four light levels, at least five light levels, or more, the subject can be considered having an improvement in the vision (e.g., visual function and / or functional vision).

[0061] In some embodiments, the evaluation test (e.g., the first wayfinding test) and the follow-up evaluation test (e.g., the second wayfinding test) can be at least about 1 week apart, at least about 2 weeks apart, at least about 3 weeks apart, at least about 4 weeks apart, at least about 5 weeks apart, at least about 6 weeks apart, at least about 7 weeks apart, at least about 8 weeks apart, at least about 3 months apart, at least about 4 months apart, at least about 5 months apart, at least about 6 months apart, at least about 7 months apart, at least about 8 months apart, at least about 9 months apart, at least about 10 months apart, at least about 11 months apart, at least about 12 months apart, at least about 1.2 years apart, at least about 1.4 years apart, at least about 1.6 years apart, at leastWSGR Docket No. 62351-711.601 about 1.8 years apart, at least about 2 years apart, at least about 3 years apart, at least about 4 years apart, at least about 5 years apart or more.

[0062] In some embodiments, the first wayfinding course of the evaluation test, and the second wayfinding course of the follow-up evaluation test can be the same. In some embodiments, the first wayfinding course of the evaluation test, and the second wayfinding course of the follow-up evaluation test can be different.

[0063] The ability to conduct both an initial and follow-up tests (e.g., an evaluation test and a follow-up evaluation test) to assess the subject’s vision (e.g., a subject with low vision) is a significant improvement over conventional assessments as the results obtained using the conventional assessments cannot be performed reliably, even at the highest luminance level for patients with low vision. The methods and systems described herein overcome this limitation by developing a more simplified wayfinding test, such that the test may be better suited for a subject with low vision.

[0064] In some embodiments, the methods and systems described herein may comprise performing the evaluation test and the follow-up evaluation test to assess the disease progression (e.g., severity of the disease advancement, rate of the disease advancement). In some embodiments, the methods and systems described herein may comprise performing the evaluation test or the follow-up evaluation test prior to the subject undergoing the ophthalmic treatment, e.g., ocular therapy, surgery, and / or gene therapy. In some embodiments, the methods and systems described herein may comprise performing the evaluation test or the follow-up evaluation test after the subject undergoing the ophthalmic treatment, e.g., ocular therapy, surgery, and / or gene therapy. In some embodiments, the methods and systems described herein may comprise performing the evaluation test prior to the subject undergoing the ophthalmic treatment, e.g., ocular therapy, surgery, and / or gene therapy, and performing the follow-up evaluation test afterwards. In some embodiments, the method is repeated (e.g., at least once, at least twice, at least three times, or more) over a recovery period of the subject to monitor improvement or decline associated with the ocular therapy, surgery, and / or gene therapy. In some embodiments, the subject is a human.Patients

[0065] Provided herein are methods and systems to evaluate vision of a subject. In some embodiments, the subject has normal functional vision. In some embodiments, theWSGR Docket No. 62351-711.601 subject is suspected of having vision impairment or deficiency in one or both eyes. In some embodiments, the subject has a retinal or ocular disease that impacts the photoreceptors in one or both eyes. In some embodiments, the subject described herein can be a subject with impaired vision or low vision. The term “impaired vision” or “low vision” are used interchangeably and are intended to refer to a significant reduction in the ability to see. In some embodiments, subjects with impaired vision may have difficulty performing everyday tasks like reading, recognizing faces, or navigating environments, even with corrective measures. In some embodiments, a subject with impaired vision or low vision can be characterized by having (1) reduced visual acuity (e.g., low visual acuity or profound visual acuity), (2) restricted visual field, and / or (3) difficulty with daily tasks. In some embodiments, a subject with impaired vision or low vision can be characterized by having low functional vision or visual function.

[0066] In some embodiments, the subject is a candidate for local or systemic ophthalmic treatment, e.g., ocular therapy, surgery, gene therapy, or a combination thereof, for one or both eyes. The ocular therapy, surgery, or the gene therapy can be for treatment of retinitis pigmentosa (RP), Leber’s congenital amaurosis (LCA), Stargardt disease, Usher’s syndrome, choroideremia, a rod-cone or cone-rod dystrophy, a ciliopathy, a mitochondrial disorder, progressive retinal atrophy, a degenerative retinal disease, age related macular degeneration (AMD), wet AMD, dry AMD, geographic atrophy, a familial or acquired maculopathy, a retinal photoreceptor disease, a retinal pigment epithelial -based disease, diabetic retinopathy, cystoid macular edema, uveitis, retinal detachment, traumatic retinal injury, iatrogenic retinal injury, macular holes, macular telangiectasia, a ganglion cell disease, an optic nerve cell disease, glaucoma, optic neuropathy, ischemic retinal disease, retinopathy of prematurity, retinal vascular occlusion, familial macroaneurysm, a retinal vascular disease, an ocular vascular diseases, a vascular disease, or ischemic optic neuropathy.

[0067] The term “visual acuity” refers to the eye's ability to discern fine details of objects and is typically measured using standardized charts, such as the Snellen chart, where visual acuity is expressed as a fraction (e.g., 20 / 20). The numerator indicates the distance at which the test is conducted, typically 20 feet, while the denominator refers to the distance at which an individual with normal vision can recognize the same detail. For example, a visual acuity of 20 / 40 best corrected visual activity (BCVA) denotes that the individual can discern details at 20 feet that a person with normal vision can distinguishWSGR Docket No. 62351-711.601 at 40 feet. In some embodiments, a visual acuity can be described using Logarithmic Measure of Angle of Resolution (LogMAR). LogMAR and BCVA can be used interchangeably to describe visual acuity of a subject. The formula for converting decimal visual acuity measurements to LogMAR is LogMAR = -log(decimal acuity).Table 1. Visual acuity scales

[0068] The terms “low visual acuity” or “profound visual acuity” are used interchangeably and refer to a significant reduction in the eye's ability to discern fine details of objects. For example, in some embodiments, a subject with low vision can be a subject with about 20 / 100 to light perception. In some embodiments, a subject with low vision can have a low visual acuity of about 20 / 100 to about 20 / 1000. In some embodiments, a subject with low vision (e.g., as expressed by visual acuity) can be a subject with about 20 / 100 to about 20 / 200, about 20 / 100 to about 20 / 300, about 20 / 100 to about 20 / 400, about 20 / 100 to about 20 / 500, about 20 / 100 to about 20 / 600, about 20 / 100 to about 20 / 700, about 20 / 100 to about 20 / 800, about 20 / 100 to about 20 / 850, about 20 / 100 to about 20 / 900, about 20 / 100 to about 20 / 950, about 20 / 100 to about 201000, about 20 / 200 to about 20 / 300, about 20 / 200 to about 20 / 400, about 20 / 200 to about 20 / 500, about 20 / 200 to about 20 / 600, about 20 / 200 to about 20 / 700, about 20 / 200 to about 20 / 800, about 20 / 200 to about 20 / 850, about 20 / 200 to about 20 / 900, about 20 / 200 to about 20 / 950, about 20 / 200 to about 201000, about 20 / 300 to about 20 / 400, about 20 / 300 to about 20 / 500, about 20 / 300 to about 20 / 600, about 20 / 300 to aboutWSGR Docket No. 62351-711.60120 / 700, about 20 / 300 to about 20 / 800, about 20 / 300 to about 20 / 850, about 20 / 300 to about 20 / 900, about 20 / 300 to about20 / 950, about 20 / 300 to about 201000, about 20 / 400 to about 20 / 500, about 20 / 400 to about 20 / 600, about 20 / 400 to about 20 / 700, about 20 / 400 to about 20 / 800, about 20 / 400 to about 20 / 850, about 20 / 400 to about 20 / 900, about 20 / 400 to about 20 / 950, about 20 / 400 to about 201000, about 20 / 500 to about 20 / 600, about 20 / 500 to about 20 / 700, about 20 / 500 to about 20 / 800, about 20 / 500 to about 20 / 850, about 20 / 500 to about 20 / 900, about 20 / 500 to about 20 / 950, about 20 / 500 to about 201000, about 20 / 600 to about 20 / 700, about 20 / 600 to about 20 / 800, about 20 / 600 to about 20 / 850, about 20 / 600 to about 20 / 900, about 20 / 600 to about 20 / 950, about 20 / 600 to about 20 / 1000, about 20 / 700 to about 20 / 800, about 20 / 700 to about 20 / 850, about 20 / 700 to about 20 / 900, about 20 / 700 to about 20 / 950, about 20 / 700 to about 201000, about 20 / 800 to about 20 / 850, about 20 / 800 to about 20 / 900, about 20 / 800 to about 20 / 950, about 20 / 800 to about 201000, about 20 / 850 to about 20 / 900, about 20 / 850 to about 20 / 950, about 20 / 850 to about 201000, about 20 / 900 to about 20 / 950, about 20 / 900 to about 201000, or about 20 / 950 to about 20 / 1000. In some embodiments, a subject with low vision (e.g., as expressed by visual acuity) can be a subject with about 20 / 100, about 20 / 200, about 20 / 300, about 20 / 400, about 20 / 500, about 20 / 600, about 20 / 700, about 20 / 800, about 20 / 850, about 20 / 900, about 20 / 950, or about 20 / 1000. In some embodiments, a subject with low vision (e.g., as expressed by visual acuity) can be a subject with at most about 20 / 200, at most about 20 / 300, at most about 20 / 400, at most about 20 / 500, at most about 20 / 600, at most about 20 / 700, at most about 20 / 800, at most about 20 / 850, at most about 20 / 900, at most about 20 / 950, or at most about 20 / 1000. In embodiments where the subject is unable to read the chart at any distance, the subject may nonetheless have light perception (LP).

[0069] In some embodiments, a subject with low vision (e.g., as expressed by visual acuity) can be a subject with LogMAR value of about 1.0 to about 2.0. In some embodiments, a subject with low vision (e.g, as expressed by visual acuity) can be a subject with LogMAR value of about 1.0 to about 1.15, about 1.0 to about 1.3, about 1.0 to about 1.45, about 1.0 to about 1.5, about 1.0 to about 1.55, about 1.0 to about 1.6, about 1.0 to about 1.65, about 1.0 to about 1.7, about 1.0 to about 1.8, about 1.0 to about 1.9, about 1.0 to about 2.0, about 1.15 to about 1.3, about 1.15 to about 1.45, about 1.15 to about 1.5, about 1.15 to about 1.55, about 1.15 to about 1.6, about 1.15 to about 1.65, about 1.15 to about 1.7, about 1.15 to about 1.8, about 1.15 to about 1.9, about 1.15 toWSGR Docket No. 62351-711.601 about 2.0, about 1.3 to about 1.45, about 1.3 to about 1.5, about 1.3 to about 1.55, about 1.3 to about 1.6, about 1.3 to about 1.65, about 1.3 to about 1.7, about 1.3 to about 1.8, about 1.3 to about 1.9, about 1.3 to about 2.0, about 1.45 to about 1.5, about 1.45 to about 1.55, about 1.45 to about 1.6, about 1.45 to about 1.65, about 1.45 to about 1.7, about 1.45 to about 1.8, about 1.45 to about 1.9, about 1.45 to about 2.0, about 1.5 to about 1.55, about 1.5 to about 1.6, about 1.5 to about 1.65, about 1.5 to about 1.7, about1.5 to about 1.8, about 1.5 to about 1.9, about 1.5 to about 2.0, about 1.55 to about 1.6, about 1.55 to about 1.65, about 1.55 to about 1.7, about 1.55 to about 1.8, about 1.55 to about 1.9, about 1.55 to about 2.0, about 1.6 to about 1.65, about 1.6 to about 1.7, about1.6 to about 1.8, about 1.6 to about 1.9, about 1.6 to about 2.0, about 1.65 to about 1.7, about 1.65 to about 1.8, about 1.65 to about 1.9, about 1.65 to about 2.0, about 1.7 to about 1.8, about 1.7 to about 1.9, about 1.7 to about 2.0, about 1.8 to about 1.9, about 1.8 to about 2.0, or about 1.9 to about 2.0. In some embodiments, a subject with low vision (e.g., as expressed by visual acuity) can be a subject with LogMAR value of about 1, about 1.15, about 1.3, about 1.45, about 1.5, about 1.55, about 1.6, about 1.65, about 1.7, about 1.8, about 1.9, or about 2.0. In some embodiments, a subject with low vision (e.g., as expressed by visual acuity) can be a subject with LogMAR value of at most about 1.15, at most about 1.3, at most about 1.45, at most about 1.5, at most about 1.55, at most about 1.6, at most about 1.65, at most about 1.7, at most about 1.8, at most about1.9, or at most about 2.0.

[0070] The term “visual field” refers to the total area in which an object can be seen in the side (peripheral) vision as the subject focuses his or her eyes on a central point. In some embodiments, a subject with low vision (e.g., as assessed by visual field) can be a subject with a visual field about 1 degree to about 20 degrees. In some embodiments, a subject with low vision (e.g., as assessed by visual field) can be a subject with a visual field about 20 degrees to about 15 degrees, about 20 degrees to about 10 degrees, about 20 degrees to about 9 degrees, about 20 degrees to about 8 degrees, about 20 degrees to about 7 degrees, about 20 degrees to about 6 degrees, about 20 degrees to about 5 degrees, about 20 degrees to about 4 degrees, about 20 degrees to about 3 degrees, about 20 degrees to about 2 degrees, about 20 degrees to about 1 degree, about 15 degrees to about 10 degrees, about 15 degrees to about 9 degrees, about 15 degrees to about 8 degrees, about 15 degrees to about 7 degrees, about 15 degrees to about 6 degrees, about 15 degrees to about 5 degrees, about 15 degrees to about 4 degrees, about 15 degrees toWSGR Docket No. 62351-711.601 about 3 degrees, about 15 degrees to about 2 degrees, about 15 degrees to about 1 degree, about 10 degrees to about 9 degrees, about 10 degrees to about 8 degrees, about 10 degrees to about 7 degrees, about 10 degrees to about 6 degrees, about 10 degrees to about 5 degrees, about 10 degrees to about 4 degrees, about 10 degrees to about 3 degrees, about 10 degrees to about 2 degrees, about 10 degrees to about 1 degree, about 9 degrees to about 8 degrees, about 9 degrees to about 7 degrees, about 9 degrees to about 6 degrees, about 9 degrees to about 5 degrees, about 9 degrees to about 4 degrees, about 9 degrees to about 3 degrees, about 9 degrees to about 2 degrees, about 9 degrees to about 1 degree, about 8 degrees to about 7 degrees, about 8 degrees to about 6 degrees, about 8 degrees to about 5 degrees, about 8 degrees to about 4 degrees, about 8 degrees to about 3 degrees, about 8 degrees to about 2 degrees, about 8 degrees to about1 degree, about 7 degrees to about 6 degrees, about 7 degrees to about 5 degrees, about 7 degrees to about 4 degrees, about 7 degrees to about 3 degrees, about 7 degrees to about2 degrees, about 7 degrees to about 1 degree, about 6 degrees to about 5 degrees, about 6 degrees to about 4 degrees, about 6 degrees to about 3 degrees, about 6 degrees to about 2 degrees, about 6 degrees to about 1 degree, about 5 degrees to about 4 degrees, about 5 degrees to about 3 degrees, about 5 degrees to about 2 degrees, about 5 degrees to about 1 degree, about 4 degrees to about 3 degrees, about 4 degrees to about 2 degrees, about 4 degrees to about 1 degree, about 3 degrees to about 2 degrees, about 3 degrees to about 1 degree, or about 2 degrees to about 1 degree. In some embodiments, a subject with low vision (e.g., as assessed by visual field) can be a subject with a visual field about 20 degrees, about 15 degrees, about 10 degrees, about 9 degrees, about 8 degrees, about 7 degrees, about 6 degrees, about 5 degrees, about 4 degrees, about 3 degrees, about 2 degrees, or about 1 degree. In some embodiments, a subject with low vision (e.g., as assessed by visual field) can be a subject with a visual field at most about 20 degrees, at most about 15 degrees, at most about 10 degrees, at most about 9 degrees, at most about 8 degrees, at most about 7 degrees, at most about 6 degrees, at most ab out 5 degrees, at most about 4 degrees, at most about 3 degrees, at most about 2 degrees, or at most about 1 degree.

[0071] For example, a subject with low vision can have (1) less than about 20 / 200 (or at least about 1.00 LogMAR) visual acuity and (2) less than 10 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 300 (or about 1.18 LogMAR) visual acuity and (2) less than 10 degrees of centralWSGR Docket No. 62351-711.601 visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 400 visual acuity and (2) less than 10 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 500 visual acuity and (2) less than 10 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 600 visual acuity and (2) less than 10 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 700 visual acuity and (2) less than 10 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 800 visual acuity and (2) less than 10 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 900 visual acuity and (2) less than 10 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 1000 visual acuity and (2) less than 10 degrees of central visual field. For example, a subject with low vision can have (1) less than about 20 / 200 (or at least about 1.00 LogMAR) visual acuity and (2) less than 8 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 300 (or about 1.18 LogMAR) visual acuity and (2) less than 8 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 400 visual acuity and (2) less than 8 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 500 visual acuity and (2) less than 8 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 600 visual acuity and (2) less than 8 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 700 visual acuity and (2) less than 8 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 800 visual acuity and (2) less than 8 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 900 visual acuity and (2) less than 8 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 800 visual acuity and (2) less than 8 degrees of central visual field. For example, a subject with low vision can have (1) less than about 20 / 200 (or at least about 1.00 LogMAR) visual acuity and (2) less than 5 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 300 (or about 1.18 LogMAR) visual acuity and (2) less than 5 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 400 visual acuity and (2) less than 5 degrees of central visual field. In some embodiments, a subjectWSGR Docket No. 62351-711.601 with low vision can have (1) less than about 20 / 500 visual acuity and (2) less than 5 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 600 visual acuity and (2) less than 5 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 700 visual acuity and (2) less than 5 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 800 visual acuity and (2) less than 5 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 900 visual acuity and (2) less than 5 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 500 visual acuity and (2) less than 5 degrees of central visual field. For example, a subject with low vision can have (1) less than about 20 / 200 (or at least about 1.00 LogMAR) visual acuity and (2) less than 2 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 300 (or about 1.18 LogMAR) visual acuity and (2) less than 2 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 400 visual acuity and (2) less than 2 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 500 visual acuity and (2) less than 2 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 600 visual acuity and (2) less than 2 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 700 visual acuity and (2) less than 2 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 800 visual acuity and (2) less than 2 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 900 visual acuity and (2) less than 2 degrees of central visual field. In some embodiments, a subject with low vision can have (1) less than about 20 / 200 visual acuity and (2) less than 2 degrees of central visual field.Kits

[0072] A kit-of-parts comprising the system described herein (e.g., a plurality of wayfinding courses, LED lights, light-controllable system, etc.) optionally together with instructions for use is further provided. For convenience, the kit-of-parts may comprise (1) a plurality of wayfinding courses, (2) a plurality of lights, (3) light-controllable systems configured to control illumination levels, (4) a video-recording device configured to record a movement, or a combination thereof. In some embodiments, theWSGR Docket No. 62351-711.601 kit may comprise one or more components necessary to implement the invention, including but not limited to the apparatus, devices, or systems for detecting movements or assessing mobility, as well as any relevant computer systems or software configured to analyze the collected data.

[0073] Additionally, the kit may include instructions for assembling, configuring, or using the components, ensuring proper operation in accordance with the described methods. The instructions may cover various test procedures, including preparation, execution, and analysis of results.

[0074] In addition to the above components, instructions for use may be provided in a kit. These instructions may be presented in the kit in a variety of forms, such as printed information on a suitable medium or substrate (e.g., a piece or pieces of paper on which the information is printed), in the packaging of the kit, in a package insert, etc. In some embodiments, instructions for use can be provided on a computer readable medium (e.g., jump / thumb drive, CD, etc.), or which the information has been recorded, or at a website address which may be used via the internet to access the information at a website.Computer Control System

[0075] The present disclosure provides computer control systems that are programmed to implement methods of the disclosure. In some embodiments, a computer system is programmed or otherwise configured to interface with an apparatus that is configured to detect one or more movements or mobility patterns of the subject (e.g., time, direction, location and / or speed), patient data, and / or configured to manipulate illumination levels or detect illumination levels. The computer system can be an electronic device of a user or a computer system that is remotely located with respect to the electronic device. The electronic device can be a mobile electronic device.

[0076] In some embodiments, a computer system includes a central processing unit (CPU, also "processor" and "computer processor" herein, which can be a single core or multi core processor, or a plurality of processors for parallel processing.

[0077] In some embodiments, a computer system also includes memory or memory location (e.g., random-access memory, read-only memory, flash memory), electronic storage unit (e.g., hard disk), communication interface (e.g., network adapter) for communicating with one or more other systems, and peripheral devices, such as cache, other memory, data storage and / or electronic display adapters. In some embodiments, the memory, storage unit, interface and peripheral devices are in communication with the CPU through aWSGR Docket No. 62351-711.601 communication bus, such as a motherboard. In some embodiments, the storage unit can be a data storage unit (or data repository) for storing data. In some embodiments, the computer system is operatively coupled to a computer network ("network") with the aid of the communication interface. In some embodiments, the network can be the Internet, an internet and / or extranet, or an intranet and / or extranet that is in communication with the Internet. In some embodiments, the network is a telecommunication and / or data network. The network can include one or more computer servers, which can enable distributed computing, such as cloud computing. In some embodiments, the network, in some cases with the aid of the computer system can implement a peer-to-peer network, which may enable devices coupled to the computer system to behave as a client or a server. In some embodiments, the CPU executes a sequence of machine-readable instructions, which can be embodied in a program or software. The instructions may be storedin a memory location, such as the memory. The instructions can be directed to the CPU, which can subsequently program or otherwise configure the CPU to implement methods of the present disclosure. Examples of operations performed by the CPU can include fetch, decode, execute, and writeback. In some embodiments, the CPU can be part of a circuit, such as an integrated circuit. One or more other components of the system can be included in the circuit. In some cases, the circuit is an application specific integrated circuit (ASIC). In some embodiments, the storage unit can store files, such as drivers, libraries and saved programs. The storage unit can store user data, e.g., user preferences and user programs. The computer system in some cases can include one or more additional data storage units that are external to the computer system, such as located on a remote server that is in communication with the computer system through an intranet or the Internet. In some embodiments, the computer system communicates with one or more remote computer systems through the network. For instance, the computer system can communicate with a remote computer system of a user. Examples of remote computer systems include personal computers (e.g., portable PC), slate or tablet PC's telephones, Smart phones, or personal digital assistants. The user can access the computer system via the network.

[0078] Methods as described herein can be implemented by way of machine (e.g., computer processor) executable code stored on an electronic storage location of the computer system, such as, for example, on the memory or electronic storage unit. The machine executable or machine-readable code can be provided in the form of software. During use, the code can be executed by the processor. In some cases, the code can be retrieved from the storage unit and stored on the memory for ready access by the processor. In some situations,WSGR Docket No. 62351-711.601 the electronic storage unit can be precluded, and machine-executable instructions are stored on memory. In some embodiments, the code can be pre-compiled and configured for use with a machine having a processor adapted to execute the code or can be compiled during runtime. The code can be supplied in a programming language that can be selected to enable the code to execute in a pre-compiled or as-compiled fashion.

[0079] Aspects of the systems and methods provided herein, such as the computer system, can be embodied in programming. Various aspects of the technology may be thought of as "products" or "articles of manufacture" typically in the form of machine (or processor) executable code and / or associated data that is carried on or embodied in a type of machine readable medium. Machine- executable code can be stored on an electronic storage unit, such as memory (e.g., read-only memory, random-access memory, flash memory) or a hard disk. "Storage" type media can include any or all of the tangible memory of the computers, processors or the like, or associated modules thereof, such as various semiconductor memories, tape drives, disk drives and the like, which may provide non -transitory storage at any time for the software programming. All or portions of the software may at times be communicated through the Internet or various other telecommunication networks. Such communications, for example, may enable loading of the software from one computer or processor into another, for example, from a management server or host computer into the computer platform of an application server. Thus, another type of media that may bear the software elements includes optical, electrical and electromagnetic waves, such as used across physical interfaces between local devices, through wired and optical landline networks and over various air-links. The physical elements that carry such waves, such as wired or wireless links, optical links or the like, also may be considered as media bearing the software. As used herein, unless restricted to non -transitory, tangible "storage" media, terms such as computer or machine "readable medium" refer to any medium that participates in providing instructions to a processor for execution.

[0080] A machine readable medium, such as computer-executable code, may take many forms, including but not limited to, a tangible storage medium, a carrier wave medium or physical transmission medium. Non-volatile storage media include, for example, optical or magnetic disks, such as any of the storage devices in any computer(s) or the like, such as may be used to implement the databases, etc. shown in the drawings. Volatile storage media include dynamic memory, such as the main memory of such a computer platform. Tangible transmission media include coaxial cables; copper wire and fiber optics, including the wires that comprise a bus within a computer system. Carrier-wave transmission media may take theWSGR Docket No. 62351-711.601 form of electric or electromagnetic signals, or acoustic or light waves such as those generated during radio frequency (RF) and infrared (IR) data communications. Common forms of computer- readable media therefore include for example: hard disk, magnetic tape, any other magnetic medium, a CD-ROM, DVD or DVD-ROM, any other optical medium, punch cards paper tape, any other physical storage medium with patterns of holes, a RAM, a ROM, a PROM and EPROM, a FLASH -EPROM, any other memory chip or cartridge, a carrier wave transporting data or instructions, cables or links transporting such a carrier wave, or any other medium from which a computer may read programming code and / or data. Many of these forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution. In some embodiments, a computer system described herein can include or be in communication with an electronic display that comprises a user interface (UI) for providing, for example, one or more results (immediate results or archived results from a previous experiment), one or more user inputs, reference values from a library or database, or a combination thereof. Examples of UIs include, without limitation, a graphical user interface (GUI) and web -based user interface.

[0081] Further, methods and systems of the present disclosure can be implemented by way of one or more algorithms. An algorithm can be implemented by way of software upon execution by the central processing unit. The algorithm can, for example, determine optimized conditions via supervised learning to optimize conditions such as a buffer type, a buffer concentration, a temperature, an incubation period, thresholds, diagnostic / prognostic indications for methods described herein.EXAMPLES

[0082] The following examples are included for illustrative purposes only and are not intended to limit the scope of the invention.EXAMPLE 1: Wayfinding Mobility Maze Design Clinical Data Acquisition: Observational Study

[0083] An observational study (NCT06375239) is designed to support the qualification of endpoints for subjects with vision in the same range as those who will be enrolled in the planned clinical study (RTx-015-CP-101). During the initial exploratory visits of this study from 1 March 2024 to 31 June 2024, ten subjects with visual acuity ranging from 20 / 200 to 20 / 6000 were introduced to a simplified mobility test (e.g., a way finding test, also referred as MLMTw). Initially two versions were introduced to patients to simulateWSGR Docket No. 62351-711.601 street-crossing or walking on a sidewalk, with one version containing a dark background with white striped borders and the other with one solid white path against a dark background. The solid white path resulted in several complaints of glare and difficulty finding an edge to visually track consistently. The most well received and consistent feedback resulted in a final version on a dark gray background with two white stripes demarcating either side of the path. The width of the stripes was set to be the same as the widest stripe on the grating acuity test for patients who are at the maximum measurable range of 20 / 8000 as measured from 1 meter. The distance separating the two stripes was explored in patients with a variety of body types, and a separation of 20” was selected.

[0084] It is noted that the eyes of patients performing the test will be further than 1 meter from the white striped path but to maximize test set-up and create patterns that have some variation to reduce memorization, the same width of 5” (-12.7 cm) was maintained.

[0085] To increase complexity and test sensitivity over a range of performance abilities, patterns consisting of four 90-degree right and left turns were created. Six patterns could be created when combining these right angle turns into four possible turns per pattern (e.g., right, right, left, left; FIG. 1). A total length of 23 feet (7.0 m) maximized the space for the mat to contain the most turns and to be situated with lighting around the outside edge within a large empty room. The test was designed to be potentially replicated at other specialized testing facilities. With the four of the patterns, patients could be started at one end, or the other, with a total of ten possible pattern orientations. The ordering of the patterns could be randomized with the end of the mobility course marked with a moveable diagonal striped cross hatch pattern laid across the exit. The material used was a matte vinyl with pattern printed on its surface. A computer-controlled system allows lux levels to be preset followed by precise exploration of light levels. The steps between each level were with 0.5 log step intervals. The lowest and highest level practically measurable ranges were 0.10 lux and 1000 lux. Beyond 1000 lux was consistently noted as causing photophobia and discomfort for subjects. The illuminance (light falling on the ground) was measured with lux meters placed in three locations across the pattern on the floor to ensure even and controlled illumination.Multi-LuminanceWSGR Docket No. 62351-711.601

[0086] Illuminance Levels in 0.5 log steps were used comprising the nine levels: 0.10, 0.32, 1.0, 3.2, 10.0, 32, 100, 320, 1000 lux.Utility of Obstacles

[0087] Moveable obstacles of varying height, width and contrast were also explored within or on the edge of the pathway with the highest comfortable lighting. None of the patients could detect them accurately by calling out / describing from a nominal distance nor detect them prior to running into them. Patients often described the objects as interrupting the path but they could not detect why the path was interrupted resulting in confusion or uncertainty as to which direction to take. Patients also typically had very small visual fields (<10 degrees diameter) and could not detect both stripes or borders to the pathway at the same time so they were given an option during the practice sessions (FIGs. 2A-2B)Inclusion of A Single, Lower Contrast, Wayfinding Stripe for Better Seeing Patients

[0088] For patients in a range closer to 20 / 200 and / or who had visual fields with larger diameters or an inferior spared island of vision, the wayfinding path was fairly easy and one patient did not seem to have difficulty until the lowest levels. This type of performance may present a ceiling type of effect. To create more difficulty, light gray background to the white stripes (or lower contrast) versions of the same patterns were explored resulting in an optimal level of 25% contrast. This version allowed for navigation or “passing” at the higher light levels but poor / incomplete navigation at mid - levels. The use of the highest contrast version or the low contrast version would be determined for each study subject at the baseline visit following a practice session. Whatever version was used at baseline would then be used for all following study visits throughout the study. There would be no mixing of versions from high to low or vice versa throughout the study for any individual subject.Data Capture

[0089] Two video cameras at either end of the room were used to capture each test trial at each lighting level. Both videos were used for review and scoring. The videos were taken with DSLR cameras that can be set to black and white and with settings that mask the light levels when graders review the trials.Testing Algorithm: practice sessionsWSGR Docket No. 62351-711.601

[0090] A test session included a practice session to familiarize the patient with the testing at higher light levels. When the patient was able to successfully navigate from the start to the end of the pathway, the light level was lowered to demonstrate the concept of testing in low levels that ultimately resulted in the inability to complete testing. One of the patterns was used with the patient navigating through the front or back opening / entrance to vary the pattern during practice.Testing Algorithm: Establishing “no pass ” level

[0091] Once the examiners felt confident of the patient’s ability and a light level was tentatively established for poor function (likely a “no pass”), the patient was dark adapted for 20 minutes. Testing began at two light levels lower than the estimated no pass level determined during practice. The patient was allowed to acclimate to the lower light level for an additional 10 minutes while the test was being set up in order to avoid delays but also continued to the dark adaptation process.Testing algorithm: Multi-Luminance Testing Strategy

[0092] The patient viewed a wall and did not watch set-up and used headphones to avoid any set-up noises that could indicate what pattern will be used. The trial pattern was randomly selected. For sub -threshold testing, a single trial was used to establish complete no-pass levels (e.g., patient stands at the start and cannot see striped lines to begin the test). As the light level is increased one step at a time, the patient’s ability to navigate the test increases. Two trials were taken at each level that brackets the patient’s ability to have pass or no-pass trials. Two trials allowed for observation of consistency. A third trial was completed if the examiner believed one of the trials was an outlier and did not represent consistent patient performance. Once the patient appeared to reach a light level that allowed them successful navigation or passing and two trials confirm this performance, a higher light level (if there are still higher light levels available) was tested at least once to confirm a passing threshold was established. After the practice session, examiners did not speak to the patient or discuss anything about the testing during each testing trial once the examiner called out “start” until the patient called out “finish or end”.Test Scoring: Pass / No Pass Criteria:

[0093] Both feet remained within the outer edges of the stripes that comprise the pathway’s borders. Patients were provided rules that each foot should not touch either stripe, however, with profound impairment, visualizing their own feet can be extremelyWSGR Docket No. 62351-711.601 difficult if not impossible while maintaining balance with forward movement, therefore each foot was allowed to touch the white but should not cross over completely to the outside of either stripe at any point.

[0094] The time taken to complete the trial start to finish was recorded at the end of practice sessions. Three times this trial time was used to denote a “no pass” trial for patients during their more difficult lighting levels. This time-to-completion period was explored with various patients and three times was determined to align with severe difficulty and still allows for patients to have varying gaits and pace at their better functioning levels without extending the testing and causing patient fatigue and frustration. Example: if it takes 60 seconds to complete in higher light levels, 180 seconds (3 minutes) would be used as a no-pass designation.

[0095] The examiner recorded all sessions, patterns used, notes about the session, whether it seemed to be a pass or no pass. This guided the determination of when trials should be repeated at near threshold levels and to ensure enough video trials were taken.

[0096] Trials and videos were named with three-digit codes masking the light level and sent separately to two masked graders who are orientation and mobility specialists. Each grader recorded the timing and the accuracy of each trial to determine a pass or no -pass designation. This information was sent back to the examiner at the Vision Research and Assessment Institute (VRAI) to unmask the scoring on the patient’s source document to determine a threshold light level for first passing level. If there were two sub-threshold trials for the same light level that returned inconsistent between grader and between trials (one pass, one no-pass), those trials were sent back to the graders for adjudication until consensus was reached.

[0097] The first light level recorded as a passing level (testing from lower to higher illumination) was recorded for that testing session and later visits was compared to that same level. For example, a patient at baseline passes at 32 lux should pass at that same light level at future visits unless a treatment effect is noted.

[0098] Two light levels of change or change in pass level score of 2 or higher were considered meaningful. For example, if a patient has a first-pass of 32 lux at baseline (Pass Score = 5), then if able to pass at 3.2 lux on a future visit (Pass Score = 7), then improvement would be meaningful (change in Pass Score = 2). If however, they were able to pass at 10 lux (Pass Score = 6) but not at 3.2 lux, this would be only one lightWSGR Docket No. 62351-711.601 level improvement and may not be beyond test-retest reliability (change in Pass Score = 1).

[0099] If a patient cannot pass any light level, they were assigned a light level beyond the highest level of 1000 at the next log step (3200). This can be used to determine if there is any change or improvement in an interventional trial.

[0100] Light levels were converted to a scale of 1 through 10 to correspond with lux levels and to assist with statistical analysis. The scale scores were assigned in a descending direction to align with the wayfinding MLMT (MLMTw) scoring and to demonstrate that improvement in vision function would be represented by an increase in score.Table 2. Wayfinding Test Lux LevelsEXAMPLE 2: Observational Study to Assess Feasibility & Measurement Properties in Retinitis Pigmentosa Patients (NCT06375239)

[0101] 18 patients that have been previously diagnosed with advanced retinitis pigmentosa (20 / 200-20 / 8000) were tested to assess the patient’s vision. Patients underwent testing at least twice, up to 2 weeks apart. 4 subjects had off chart vision and were able to complete grating acuity and were assigned a 2.00 logMAR value for purpose of inclusion in data (FIG. 3).

[0102] The patients were subjected to the wayfinding test as described in Example 1. The way finding MLMT (MLMTw) was able to distinguish different levels of visual function. Test and retest assessments were completed on 16 of the patients with no more than 1 light level variation between visits (Table 3). Two patients were unable to return for retesting. The range of performance was distributed across 8 (levels 2-9) levels with level 1 (0.1 lux, n= 1) assigned when no fail levels occurred (passed all). Level 10 was assigned when the patient was unable to pass any light levels (3200 lux, n=4). Retesting was completed even on these extreme patients and demonstrated consistency.Performance was related to visual function with the strongest relationships in CS and diameter of VF (0.55 and 0.61 respectively) (FIG. 4 and FIG. 5).WSGR Docket No. 62351-711.601

[0103] 1 subject was not included in FIG. 4 due to incomplete grating contrast sensitivity (CS) testing. 4 subjects were not included in visual field testing due to large peripheral islands, poor reliability on testing, or no measurable central vision (FIG. 5).Table 3. Representative results* represent subjects with off chart vision that were assigned a >2.00 logMAR VA value.EXAMPLE 3: Extract from the Procedure Manual for conducting the test

[0104] The procedure manual outlined below demonstrates how the test can be executed, including the preparation phase, test initiation, data collection, and analysis of the subject's performance.

[0105] Illuminance Levels in 0.5 log steps comprising eight levels is established. These light levels include, for example, 0.10, 0.32, 1.0, 3.2, 10.0, 32, 100, 320, 1000 lux.

[0106] Low Contrast Version: In order to create more difficulty for subjects with better function, light gray background to the white stripes (or lower contrast) versions of the same patterns can be used. This version can be used if subjects pass the high contrast version at 3.2 lux or lower.WSGR Docket No. 62351-711.601

[0107] Baseline Assessment: The use of the highest contrast version or the low contrast version would be determined at the baseline visit following a practice session. Whatever version was used at baseline would then be used for all following study visits throughout the study. There would be no mixing of versions from high to low or vice versa throughout the study.

[0108] Equipment: Two video cameras at either end of the room will be used to capture each test trial in each lighting level. One main camera will be used for review and scoring with the secondary camera videos viewable to check for uncertain angles or potential blocked videos. The videos will be taken with DSLR cameras that can be set to black and white and with settings that will mask the light levels when graders review the trials from a secure online folder. Graders will return scores to the VRAI for unmasking and final recording of the pass / fail threshold.Preparation

[0109] Ensure that all windows and doors are sealed or covered so no light leaks in when testing occurs. Two people running the test enable a faster setup and execution of testing but it is possible to conduct testing with one examiner.

[0110] Access a list of random 3 -digit random numbers for video identifiers (do not repeat any identifiers on any visit for a single subject). Use a website or computer generated list such as randomnumbergenerator.com. For the patient tested that day, double check that none of the 3 -digit identifiers have been used for any video on prior visits.[OHl] Place the 3 -digit codes in the source document chart to correspond with the light levels and videos that will be collected for each mobility test. There may be up to 10 tests completed during monocular testing of each eye.

[0112] If this is not a baseline visit, review the last visit to determine the lighting ranges tested.

[0113] There are 10 possible patterns of pathways with white path borders on a black background printed on large vinyl sheets approximately 10’XI 6’. Each pathway is approximately 23 feet in length with 4 turns. There are 6 printed patterns with four of those patterns creating two possible orientations depending on which end the subject begins.WSGR Docket No. 62351-711.601

[0114] The use of the pattern for each trial should be randomized so that subjects are unable to easily anticipate the next trial.

[0115] After each trial either roll up the prior pattern to reveal the pattern beneath or unroll the next pattern. Make every effort to not repeat the use of any patterns that have been previously used during that testing session, however with limited patterns and at least 1-2 used during the practice sessions, it may be necessary to repeat a pattern.Preparation and Practice:

[0116] A test session will include a practice session to familiarize the patient with the testing at higher light levels. If it seems the patient will be able to successfully navigate from the start to the end of the pathway, the light levels will be lowered to demonstrate the concept of testing in low levels that will ultimately result in the inability to complete testing. One of the patterns will be used with the patient navigating through the front or back opening / entrance to vary the pattern during practice. Once the examiners feel confident of the patient’s ability and a light level is found that is likely to be passed at 10.0 lux or lower, the patient should be dark adapted for 30 minutes. True dark adaptation can take up to 30 minutes but is only relevant if the subject has rod function. If the fail levels are 10 lux or higher, there is no need to fully dark adapt as the patient is unlikely to have rods and testing would not change. Lack of rod function can also be confirmed with FST. The patient can adapt to the room illumination for 5-10 min during setup, however the patient should not view the set-up process (turn chair away from setup).

[0117] Start the testing session with practice using one of the test patterns. Confirm that the light level is above threshold and that the patient can follow the pathway and generally stay between the white borders.

[0118] Guide subject to start of a pattern and explain that there is a path to walk that has two white stripes on either side as guides or borders. Say “you may not be able to see both stripes at the same time, but they will act as borders for you to stay between. Try not to walk on the lines or touch them with your feet. If you can’t see both stripes, it may be easiest to identify one line / stripe and follow it to walk around the path.”

[0119] Guide the subject around the first 1 -2 turns of the path and then see if the subject can completely make it through to the end. Show the subject the striped pattern as the end of the path. See if they can step on it to designate they are done with the path . Have them say the word “stop” when they think they’ve reached it.WSGR Docket No. 62351-711.601Subject Testing:

[0120] Testing should begin at least two light levels lower than the estimated no pass level determined during practice. If no dark adaptation is needed (>10 lux), the subject will be allowed to acclimate to the lower light level for up to 10 minutes while the test is being set up and to adjust to the light level. In order to adapt to existing light levels (mesopic and photopic), the subject can remove occlusion and view a wall. Headphones may also be used to avoid auditory clues during set up. The trial patterns will be randomly selected. For sub-threshold testing, a single trial can be used to establish complete no-pass levels (e.g., subject stands at the start and cannot see striped lines to begin the test). As the light level is increased one step at a time, the subject will increase the ability to navigate the test. Two trials will be taken at each level to bracket the patient’s ability to have pass or no-pass trials. Two trials allow for observation of consistency. A third trial can be completed if the examiner believes one of the trials is an outlier and does not represent consistent patient performance.

[0121] Once the patient appears to reach a light level that allows them successful navigation or passing and two trials confirm this performance, a higher light level (if there are still higher light levels available) should be tested at least once to confirm a passing threshold was established. After the practice session, examiners should not speak to or discuss anything about the testing during each testing trial once the examiner calls out “start” and the patient calls out “finish or end”.Pass / Fail Criteria:

[0122] Both feet remain within the outer edges of the stripes that comprise the borders of the pathway.

[0123] Subjects are instructed that each foot should not touch either stripe, however, with profound impairment, visualizing their own feet can be extremely difficult if not impossible while maintaining balance with forward movement, therefore each foot is allowed to touch the white but should not cross over completely to the outside of either stripe at any point.

[0124] The time taken to complete the trial start to finish is recorded at the end of practice sessions. A multiplier of three can be used to estimate a slower pace that represents a significant decline in function and will represent a fail or no pass trial for subjects during their more difficult lighting levels. This timeout period was explored with various patients and a multiplier of three was determined to align with severeWSGR Docket No. 62351-711.601 difficulty and still allows for patients to have varying gaits and pace at their better functioning levels without extending the testing and causing patient fatigue and frustration.

[0125] Example if it takes 60 seconds to complete in higher light levels, 180 seconds (3 minutes) would be used as a no-pass threshold.

[0126] If a subject starts a trial but has extensive pause during the trial, the examiner can stop the trial once it is clear the subject cannot regain their position (e.g., walks off course and becomes lost).

[0127] If a subject walks out of the pathway, the trial is automatically a fail. If the examiner believes this is an outlier situation, they can retest the same light level again.

[0128] The examiner records all sessions, patterns used, notes about the session, whether it seems to be a pass or no pass. This will guide the determination of when trials should be repeated at near threshold levels and to ensure enough video trials are taken. Scoring and Grading

[0129] Trials and videos will be named with three-digit codes masking the light level and sent separately to two masked graders who are orientation and mobility specialists. Each grader will independently record the timing and the accuracy of each trial to determine a pass or fail (no-pass) designation. If the graders differ in scoring for a trial or set of trials, the graders will discuss and “adjudicate” the trial and reach agreement and send the VRAI examiner the final grading of Pass or Fail per trial.

[0130] The grading will be sent back to the examiner at the VRAI to unmask the scoring on the patient’s source document to determine a threshold light level for pass or no pass. The highest light level that is recorded as no pass will be recorded for that testing session and later visits will be compared to that pass. For example, a patient at baseline fails or doesn’t pass at 32 lux should fail at that same light level at future visits unless a treatment effect is noted.

[0131] Video tape / START process: Videographer starts recording and verbalizes the three digit random number for that maze followed by the word “START” loud enough for the subject to hear clearly. The camera angle should be directed at the subject’s waist or legs to avoid facial identification. The subject then either opens their eyes (one eye is patched) to immediately begin the trial. The video should be stopped after the patient says “Stop” and as they reach the final pattern at the end. Guide subjects to step acrossWSGR Docket No. 62351-711.601 the finish line as they may not correctly judge the distance from the end if they don’t make an effort to cross it with their foot / feet. If they falsely reach the end but discover they were incorrect and continue, allow them to continue to record. The videographer should note the approximate time of start and stop of recording. The precise time will be recorded by the masked video graders but the estimated time is important to track during testing so that outliers and test completion can be judged.

[0132] Sample Script: “We will start at an extremely low or dim light level and it will be very challenging. If you cannot see either of the stripes to border the pathway look around for a moment and then let me know and we will go to the next light level higher” . However, sometimes, you may adjust and start to see the path so if you think you can see it, we can try to start the pathway and we can always quit when you lose your way and increase to the next light level”. The testing will stop after several light levels and pathways. The patterns will change each time but don’t try to memorize the pathways or anticipate the turns from memory. It is very important to start each test trial with maximum effort and attention. Between trials you will rest in the chair with a sleep mask on while we set up the next pattern. Now, let’s start with sitting you in the dark for about 30 minutes with the sleep mask while your eyes adjust to the lower light. It may be a frustrating process in the lowest light levels but it will get easier as we increase the light levels”.Correction / Subject education Script:

[0133] If the subject cannot stay in the pathway the majority of the time at any light level, the examiner may attempt to re-educate and practice the subject between trials: “you are touching the stripe right now with your foot, try to re-orient yourself to stay in the path but not touching the stripe”.

[0134] If they wander off the course with both feet out of the path (one may be inadvertently on the outer path). If the examiner thinks this is due to lack of practice, stop the testing and re-educate the patient and try again on a different path pattern.

[0135] Pass: Complete the pathway with both feet within the path. Slow walking or even “shuffling” is allowed as this is primarily a detection task during movement (not specifically a mobility or timed test). Occasional inadvertent foot touches are allowed but not encouraged. Try to re-educate the subject between trials, note the re-education on the form. Time the trials in order to know if over the time limit. You may repeat a light level if you are uncertain if the performance is representative. Sometimes odd thingsWSGR Docket No. 62351-711.601 happen and patients may have an outlier type of performance. Make clear notes as to which trial(s) are to be gradedVideo Files for Scoring

[0136] Each video file should be saved using the subject ID and the three digit randomized code on the camera drive and also downloaded to a password protected location for sharing with scorers. No identifying information is recorded on the videos other than the 3 digit randomized code. Each testing day for a subject may have up to 10 videos and one day of testing videos should be kept in one folder with the date of testing on the folder name.

[0137] The graders will be masked to the exact light level of each trial. The graders are provided an excel file records whether each trial is a pass or fail with reasons noted. The time of start, end, and reasons for fail. They are given three days to complete the scoring and return the scoring sheet with any notes for each trial. Once the score sheet is returned to the VRAI (e.g., electronic file share via SharePoint) per subject.

[0138] The graders’ scores (as shown in Table 4) should be transferred to the original source docs for each visit by personnel at the VRAI.Table 4. Exemplary Grader’s Evaluation FormWSGR Docket No. 62351-711.601EXAMPLE 4: Composite scoring sheet for low light mobility test

[0139] An alternative composite scoring sheet was developed to evaluate a subject’s performance during a low light mobility test (e.g., a way finding test) conducted under multiple luminance levels. The scoring sheet was configured to capture and integrate multiple performance parameters into a unified composite score.Step 1. Determine Baseline Illuminance Level

[0140] The test begins with determining a subject’s baseline illuminance level that begins with a pass / fail staircase procedure. The test is initiated at predetermined luminance level within a range of approximately 0.1 to 1000 lux (assign 1 = 3200 lux if unable at 1000).

[0141] The time to complete the course was recorded (in sec). The result is used for initial fail / pass criteria. For example, if a subject’s completion time exceeds three times their fastest recorded time (identified during testing at the subject’s passing levels of their testing), the subject is deemed to have failed the course. The baseline test level is defined as the first illuminance level at which the subject achieves a pass immediately above a failed level. Other fail / pass criteria include when they cannot complete the course (e.g. get lost and cannot continue accurately) or when they step with one foot completely outside of one of the two white pathway lines.Table 5. Exemplary scale score:WSGR Docket No. 62351-711.601Step 2. Functional Performance at Baseline Illuminance

[0142] At the pass level, a subject performs 2 trials (3 if needed for consistency). If the subject performed 3 trials, then the median score is used. The pass score (Table 5) is recorded.

[0143] The performance by the subject is then further scored based on observational rubric’s 0-4 scale:

[0144] A. Trajectory Steadiness (Veering)1 = Stays on one side of the path > (greater than) 75% of the time;2 = Stays on one side of the path > 50% but < (less than or equal to) 75% of the time;3 = Stays on one side of the path >25% and < 50% of the time; and4 = Stays centered or on one side of the path < 25% of the time

[0145] B. Posture and head Position1 = Leans over or tilts head to see the path > 75% of the time;2 = Leans over or tilts head > 50% but < 75% of the time;3 = leans over or tilts head > 25% but < 50% of the time; and4 = Generally stands straight and has aligned head posture < 25% of the time

[0146] C. Total time to complete1 = > 45 seconds2 = > 30 seconds to < 45 sec3 = >15seconds to <30 seconds4 = 10 seconds to < 15 seconds

[0147] D. Path Completion / Closure (difficulty completing a partial visual image)1 = Unable to complete or accurately find end of course, pauses or searches visually or stops too early;WSGR Docket No. 62351-711.6012 = Uncertain of end of course, slows stride or has long pauses to search visually;3 = Identifies end of course but veers to one side or slightly off track; and4 = Identifies end of course visually and is well centered

[0148] The Functional Performance Score (FPS) is calculated as the sum of scores from A through D (e.g., 0 if unable to complete at all, a total score may range from 4 to 16).Step 3. Composite Total

[0149] In one method, the Total Composite Score is calculated by taking the sum of the pass level (e.g., a score ranging from 1 to 10) and FPS (e.g., a score ranging from 4 to 16). If the pass level is 1, then the total score is only the light level (e.g., a score of 1) and no scores from the functional performance are taken. The score of 1 indicates the worst performance. The composite score ranges from 1 to 26. In this scoring system, higher total composite scores correspond to better performance outcomes.

[0150] In another method, the Total Composite Score is calculated by taking the sum of the pass level (e.g., a score ranging from 1 to 10) X2 and FPS (e.g., a score ranging from 4 to 16). If pass level is 1, then the total composite score is only the light level and no functional categories. The total composite score of 2 indicates the worst performance. The composite score ranges from 2 to 36. In this scoring system, higher total composite scores correspond to better performance outcomes.

[0151] In another method, the Total Composite Score is calculated by taking the sum of the pass level (e.g., a score ranging from 1 to 10) X 3 and FPS (e.g., a score ranging from 4 to 16). If pass level is 1, then the total composite score is only the light level and no functional categories. The total composite score of 3 indicates the worst performance. The composite score ranges from 3 to 48. In this scoring system, higher total composite scores correspond to better performance outcomes.Other Criteria: Timing

[0152] Timing is noted at the initial pass fail step but is not used as a determination of improvement. Any given day and patient energy can impact time from day to day.Within a given day of assessment, time can be noticeably different from trials. In some cases, time is not considered as a separate factor. In some cases, time may be incorporated as a factor in calculating the composite score.WSGR Docket No. 62351-711.601

[0153] While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

Claims

WSGR Docket No. 62351-711.601CLAIMSWHAT IS CLAIMED IS:1 . A method for evaluating vision of a subject, the method comprising: a) conducting a wayfinding test by presenting a first wayfinding course to the subject, wherein the first wayfinding course comprises: a dark-colored surface, a series of light colored markings on the dark surface forming a path demarcated by two parallel lines spaced from about 40 to about 60 centimeters (cm) apart from each other and a total length of the path is from about 6 to about 8 meters, wherein the path has a starting point, at least one turn, and an ending point to guide a subject through the dark surface; b) selecting a first illumination level from a plurality of illumination levels; c) illuminating the dark-colored surface; d) recording movements of the subject from the starting point to the ending point; and e) determining the vision of the subject.

2. The method of claim 1, wherein the dark-colored surface has a length of from about 2 meters (m) to about 4 m, and a width of from about 3 m to about 7 m.

3. The method of claim 2, wherein the dark-colored surface has a length of about 3 m and a width of about 5.5 m.

4. The method of any one of claims 1 -3, wherein a width of each line of the two parallel lines is at least about 6 cm, atleast about 8 cm, at least about 10 cm, at least about 12 cm, at least about 12.5 cm, at least about 13 cm, at least about 13.5 cm or at least about 14 cm.

5. The method of claim 4, wherein a width of each line of the two parallel lines is about 12.5 cm.

6. The method of any one of claims 1 -5, wherein a distance between the two parallel lines is about 50 cm.

7. The method of any one of claims 1 -6, wherein the two parallel lines demarcating the path on the dark-colored surface have a color that exhibits at least about 25%, at least about 50%, at least about 75%, atleast about 80%, at least about 90%, or 100% contrast level to the dark-colored surface.

8. The method of any one of claims 1 -7, wherein the dark-colored surface is a blackcolored surface or a gray-colored surface.WSGR Docket No. 62351-711.6019. The method of any one of claims 1-8, wherein the two parallel lines on the darkcolored surface are white-colored lines.

10. The method of any one of claims 1 -8, wherein at least one turn comprises at least one 90-degree right or left turn.

11. The method of any one of claims 1-10, wherein the first wayfinding course has at least one turn, at least two turns, at least three turns, at least four turns, at least five turns, or at least six turns.

12. The method of claim 11, wherein the first wayfinding course has four turns.

13. The method of any one of claims 1-12, wherein the plurality of illumination levels comprises at least 7 illumination levels, at least 8 illumination levels, at least 9 illumination levels, at least 10 illumination levels, at least 11 illumination levels, at least 12 illumination levels or more.

14. The method of claim 13, wherein the plurality of illumination levels comprises 9 illumination levels.

15. The method of claim 13, wherein the plurality of illumination levels range from about 0.1 lux to about 1000 lux.

16. The method of claim 15, wherein each illumination of the plurality of illumination levels is spaced from an adjacent illumination level by about 0.5 log units.

17. The method of any one of claims 1-16, wherein the plurality of illumination levels comprise about 0.1, about 0.32, about 1.0, about 3.2, about 10.0, about 32, about 100, about 320, and about 1000 lux.

18. The method of any one of claims 1-17, wherein the first way finding course further comprises at least one obstacle.

19. The method of any one of claims 1-17, wherein the first wayfinding course has no obstacle.

20. The method of any one of claims 1-19, wherein the determining the vision of the subject comprises determining time to complete the first wayfinding course.

21. The method of any one of claims 1-20, wherein the determining the vision of the subject comprises recording at least one failure criterion.

22. The method of claim 21, wherein the atleast one failure criterion comprises touching or extending beyond either one of the two parallel lines, taking longer than a predetermined time limit, or declaring inability to proceed with the wayfinding test.WSGR Docket No. 62351-711.60123. The method of claim 22, wherein the predetermined time limit is three times a duration required to navigate from the starting point to the ending point obtained during a practice wayfinding test.

24. The method of any one of claims 1-23, wherein the determining the vision of the subject comprises determining a first passing threshold illumination level.

25. The method of claim 24, wherein the first passing threshold illumination level is a lowest illumination level that the subject successfully navigates from the starting point to the ending point of the wayfinding test.

26. The method of claim 24, wherein the first passing threshold illumination level is determined after the subject successfully navigates from the starting point to the ending point of the way finding test for at least one trial, at least two trials, at least three trials, at least four trials, or at least five trials.

27. The method of any one of claims 1-26, further comprising a) conducting a follow-up wayfinding test by presenting a second wayfinding course to the subject; b) selecting a second illumination level from the plurality of illumination levels; c) illuminating the dark-colored surface; d) recording movements of the subject; and e) determining the vision of the subject.

28. The method of claim 27, wherein the first wayfinding course and the second way finding course are the same.

29. The method of claim 27, wherein the first way finding course and the second way finding course are different.

30. The method any one of claims 27-29, wherein the first illumination level and the second illumination level are the same.

31. The method of any one of claims 27-29, wherein the first illumination level and the second illumination level are different.

32. The method of any one of claims 27-31, wherein the determining the vision of the subject of the follow-up way finding test comprises determining a second passing threshold illumination level.

33. The method of claim 32, wherein the second passing threshold illumination level comprises a lowest illumination level that the subject successfully navigates from the starting point to the ending point of the follow-up wayfinding test.WSGR Docket No. 62351-711.60134. The method of any one of claims 27-33, wherein duration between the wayfinding test and the follow-up wayfinding test is at least about 1 -month, at least about 2-month, at least about 3 -month, at least about 4 -month, at least about 5 -month, at least about 6-month, at least about 7-month, at least about 8-month, at least about 9-month, at least about 10-month, at least about 11 -month, or at least about 12-month apart.

35. The method of any one of claims 27-34, further comprising: comparing the vision assessed at the wayfinding test and the visional function assessed at the follow-up wayfinding test to determine changes or improvement.

36. The method of claim 35, wherein an improvement in the vision is achieved when the first passing threshold illumination level and the second passing threshold illumination level are different by at least two light levels, at least three light levels, at least four light levels, at least five light levels, at least six light levels, at least seven light levels, or at least eight light levels.

37. The method of any one of claims 27-36, wherein the subject is a subject with profoundly impaired vision or low vision.

38. The method of claim 37, wherein the subject with profoundly impaired vision or low vision has a visual acuity that is less than about 20 / 200, less than about 20 / 400, less than about 20 / 600, less than about 20 / 800, less than about 20 / 1000, less than about 20 / 2000, less than about 20 / 3000 or less best-corrected visual acuity (BCVA).

39. The method of claim 37 or 38, wherein the subject has greater than about 1 .0 logMAR BCVA, greater than about 1 .2 logMAR BCVA greater than about 1 .4 logMAR BCVA, greater than about 1.5 logMAR BCVA, greater than about 1 .6 logMAR BCVA, greater than about 1.7 logMARBCVA, greater than about 1.8 logMAR BCVA, 1.90 logMAR BCVA, or more.

40. The method of any one of claims 37-39, wherein the subject has less than about 10 degrees, less than about 8 degrees, less than about 6 degrees, less than about 5 degrees, less than about 4 degrees, less than about 3 degrees, or less than about 2 degrees in diameter of visual field.41 . The method of any one of claims 1 -40, wherein the subject is suspected of having or having vision impairment or deficiency in one or both eyes.

42. The method of any one of claims 1 -41, wherein the subject is a candidate for local or systemic ophthalmic treatment.

43. The method of claim 42, wherein the local or systemic ophthalmic treatment is an ocular therapy, a surgery, a gene therapy, or a combination thereof.WSGR Docket No. 62351-711.60144. The method of any one of claims 1 -43, wherein the subject has an ocular disease.

45. The method of claim 44, wherein the ocular disease is selected from the group consisting of retinitis pigmentosa (RP), Leber’s congenital amaurosis (LCA), Stargardt disease, Usher’s syndrome, choroideremia, a rod-cone or cone-rod dystrophy, a ciliopathy, a mitochondrial disorder, progressive retinal atrophy, a degenerative retinal disease, age related macular degeneration (AMD), wet AMD, dry AMD, geographic atrophy, a familial or acquired maculopathy, a retinal photoreceptor disease, a retinal pigment epithelial -based disease, diabetic retinopathy, cystoid macular edema, uveitis, retinal detachment, traumatic retinal injury, iatrogenic retinal injury, macular holes, macular telangiectasia, a ganglion cell disease, an optic nerve cell disease, glaucoma, optic neuropathy, ischemic retinal disease, retinopathy of prematurity, retinal vascular occlusion, familial macroaneurysm, a retinal vascular disease, an ocular vascular diseases, a vascular disease, and ischemic optic neuropathy.

46. The method of any one of claims 1 -45, wherein, prior to the wayfinding test or the follow-up wayfinding test, the subject is treated with an ocular therapy, an ocular surgery, and / or a gene therapy.

47. The method of any one of claims 1-46, wherein, after the wayfinding test and prior to the follow-up wayfinding test, the subject is treated with an ocular therapy, a surgery, and / or a gene therapy.

48. The method of any one of claims 1 -47, wherein the evaluating vision comprises evaluating a functional vision of the subject or evaluating a visual function of the subject.

49. A method of monitoring vision of a subject that has received at least one ophthalmic treatment, the method comprising: a) determining a first passing threshold illumination level of the subject using the method of any one of claims 1 -48 at a first time point; b) determining a second passing threshold illumination level of the subject using the method of any one of claims 1 -48 at a second time point; and c) determining effectiveness of the at least one ophthalmic treatment by comparing the first passing threshold illumination level and the second passing threshold illumination level.

50. The method of claim 49, wherein the at least one ophthalmic treatment is an ocular therapy, a surgery, a gene therapy, or a combination thereof.51 . The method of claim 50, wherein the ocular therapy, surgery, or the gene therapy is for treatment of retinitis pigmentosa (RP), Leber’s congenital amaurosis (LCA), StargardtWSGR Docket No. 62351-711.601 disease, Usher’s syndrome, choroideremia, a rod-cone or cone-rod dystrophy, a ciliopathy, a mitochondrial disorder, progressive retinal atrophy, a degenerative retinal disease, age related macular degeneration (AMD), wet AMD, dry AMD, geographic atrophy, a familial or acquired maculopathy, a retinal photoreceptor disease, a retinal pigment epithelial -based disease, diabetic retinopathy, cystoid macular edema, uveitis, retinal detachment, traumatic retinal injury, iatrogenic retinal injury, macular holes, macular telangiectasia, a ganglion cell disease, an optic nerve cell disease, glaucoma, optic neuropathy, ischemic retinal disease, retinopathy of prematurity, retinal vascular occlusion, familial macroaneurysm, a retinal vascular disease, an ocular vascular diseases, a vascular disease, or ischemic optic neuropathy.

52. The method of any one of claims 49-51, wherein the first time point and the second time point is at least about 1 -month, at least about 2-month, at least about 3 -month, at least about4-month, at least about 5 -month, at least about 6 -mon th, at least about 7-month, at least about 8-month, at least about 9-month, at least about 10-month, at least about 11 -month, or at least about 12-month apart from each other.

53. The method of any one of claims 49-52, wherein the subject receives the at least one ophthalmic treatment before the first time point.

54. The method of any one of claims 49-52, wherein the subject receives the at least one ophthalmic treatment after the first time point and before the second time point.

55. The method of any one of claims 49-52, wherein the subject receives the at least one ophthalmic treatment after the second time point.

56. The method of any one of claims 49-55, further comprising: monitoring the progress of the subject that is undergoing or has received the at least one ophthalmic treatment; and determining effectiveness of the at least one ophthalmic treatment.

57. The method of claim 56, wherein the at least one ophthalmic treatment is determined to be effective when the first passing threshold illumination level and the second passing threshold illumination level are different by at least two light levels, at least three light levels, at least four light levels, at least five light levels, at least six light levels, at least seven light levels, or at least eight light levels.

58. A way finding system comprising: a) a dark surface; b) a series of light colored markings on the dark surface forming a path demarcated by two parallel lines spaced at least about 40-60 centimeters (cm) apartWSGR Docket No. 62351-711.601 and the path has a total length of about 6-8 meters, wherein the path has a starting point, at least one turn, and an ending point to guide a subject through the dark surface; c) a light system configured to provide adjustable illumination levels; and d) a detection system configured to monitor movements of the subject from the starting point to the ending point.

59. The system of claim 58, wherein the dark-colored surface has a length of from about2 meters (m) to about 4 m, and a width of from about 3 m to about 7 m.

60. The system of claim 59, wherein the dark-colored surface has a length of about 3 m and a width of about 5.5 m.

61. The system of any one of claims 58-60, wherein a width of each line of the two parallel lines is at least about 6 cm, at least about 8 cm, at least about 10 cm, at least about 12 cm, at least about 12.5 cm, at least about 13 cm, at least about 13.5 cm or at least about 14 cm.

62. The system of claim 61, wherein a width of each line of the two parallel lines is about 12.5 cm.

63. The system of any one of claims 58-62, wherein a distance between the two parallel lines is about 50 cm.

64. The system of any one of claims 58-63, wherein the two parallel lines demarcating the path on the dark-colored surface have a color that exhibits at least about 25%, at least about 50%, at least about 75%, atleast about 80%, at least about 90%, or 100% contrast level to the dark-colored surface.

65. The system of any one of claims 58-64, wherein the dark-colored surface is a blackcolored surface or a gray-colored surface.

66. The system of any one of claims 58-65, wherein the two parallel lines on the darkcolored surface are white-colored lines.

67. The system of any one of claims 58-65, wherein at least one turn comprises at least one 90-degree right or left turn.

68. The system of any one of claims 58-67, wherein the wayfinding course has at least one turn, at least two turns, at least three turns, at least four turns, at least five turns, or at least six turns.

69. The system of claim 68, wherein the wayfinding course has four turns.

70. The system of any one of claims 58-69, wherein the light system comprises a plurality of light.WSGR Docket No. 62351-711.60171. The system of claim 70, wherein the plurality of light comprises light-emitting diodes.

72. The system of claim 71 , wherein each of the plurality of light is configured to provide a plurality of illumination levels comprising at least 7 illumination levels, at least 8 illumination levels, at least 9 illumination levels, at least 10 illumination levels, at least 11 illumination levels, at least 12 illumination levels or more.

73. The system of claim 72, wherein the plurality of illumination levels comprises 9 illumination levels.

74. The system of claim 72, wherein the plurality of illumination levels range from about 0.1 lux to about 1000 lux.

75. The system of claim 72, wherein each illumination of the plurality of illumination levels is spaced from an adjacent illumination level by about 0.5 log units.

76. The system of any one of claims 72-75, wherein the plurality of illumination levels comprise about 0.1, about 0.32, about 1.0, about 3.2, about 10.0, about 32, about 100, about 320, and about 1000 lux.

77. The system of any one of claims 58-76, wherein the wayfinding course further comprises at least one obstacle.

78. The system of any one of claims 58-76, wherein the wayfinding course has no obstacle.

79. The system of any one of claims 58-78, wherein the detecting system comprises a video-recording device configured to record a movement of the subject.

80. The system of any one of claims 58-79, wherein the system is for evaluating vision of the subject.

81. The system of claim 80, wherein the subject is a subject with profoundly impaired vision or low vision.

82. The system of claim 81, wherein the subject with profoundly impaired vision or low vision has a visual acuity that is less than about 20 / 200, less than about 20 / 400, less than about 20 / 600, less than about 20 / 800, less than about 20 / 1000, less than about 20 / 2000, less than about 20 / 3000 or less best-corrected visual acuity (BCVA).

83. The system of claim 81, wherein the subject has greater than about 1.0 logMAR BCVA, greater than about 1.2 logMAR BCVA greater than about 1.4 logMAR BCVA, greater than about 1.5 logMAR BCVA, greater than about 1.6 logMAR BCVA, greater than about 1.7 logMARBCVA, greater than about 1.8 logMAR BCVA, 1.90 logMAR BCVA, or more.WSGR Docket No. 62351-711.60184. The system of any one of claims 81-83, wherein the subject has less than about 10 degrees, less than about 8 degrees, less than about 6 degrees, less than about 5 degrees, less than about 4 degrees, less than about 3 degrees, or less than about 2 degrees in diameter of visual field.

85. A system for evaluating performance of a subject in a wayfinding test, the system comprising: a) a dark surface; b) a series of light-colored markings on the dark surface forming a path demarcated by two parallel lines, wherein the path has a starting point, at least one turn, and an ending point to guide a subject through the dark surface; c) a light system configured to provide adjustable illumination levels; and d) a scoring module configured to generate a composite score based on illuminance level and at least one performance factor comprising:(i) trajectory steadiness;(ii) posture and head position;(iii) total time to complete; and / or(iv) path completion / closure.

86. The system of claim 85, wherein the composite score is calculated as a sum of individual sub-scores corresponding to the illuminance level, the trajectory steadiness, the posture and head position, the search and / or uncertainty behaviors, the step or gait consistency, or the path completion / closure.

87. The system of claim 85 or 86, wherein a score for the illumination level is assigned a value on a scale of 1 to 10.

88. The system of claim 87, wherein the score for the illumination level is scaled by a factor of two, three, four, or five when determining the composite score.

89. The system of any one of claims 85-88, wherein a score of the at least one performance factor is assigned a value on a scale of 1 to 4.

90. The system of claim 89, wherein a score of the trajectory steadiness is based on a frequency or magnitude of deviation from a path centerline of the wayfinding test.

91. The system of claim 90, wherein a higher score of the trajectory steadiness corresponds to fewer deviations from the path centerline.

92. The system of claim 89, wherein a score of the posture and head position is based on a frequency of torso sway or head tilts.WSGR Docket No. 62351-711.60193. The system of claim 92, wherein a higher score of the posture and head position corresponds to fewer or smaller deviations from a reference torso or head orientation.

94. The system of claim 89, wherein a score of the total time to complete is based on a frequency of pauses taken by the subject or the total time to complete the way finding course by the subject.

95. The system of claim 94, wherein the pause is greater than at least about 1 second, at least about 2 seconds, at least about 3 seconds, at least about 4 seconds, or at least about 5 seconds.

96. The system of claim 94 or 95, wherein a higher score of the total time to complete corresponds to fewer or no pauses.

97. The system of claim 94, wherein a higher score of the total time to complete corresponds to faster navigation time.

98. The system of claim 89, wherein a score of the path completion / closure is based on an ability to visually or spatially complete the way finding test by the subject.

99. The system of claim 98, wherein a higher score of the path completion / closure corresponds to accurate and continuous navigation during the way finding test by the subject.

100. The system of any one of claims 85-99, wherein the composite score is defined within a range from 1 to 30, from 2 to 40, or from 3 to 50.

101. The system of claim 100, wherein a higher score corresponds to better performance.

102. The system of any one of claims 85-101, wherein the scoring module is further configured to incorporate completion time as a factor in the composite score.

103. The system of any one of claims 85-101, wherein the scoring module does not incorporate completion time as a factor in the composite score.

104. The system of any one of claims 85-103, wherein the scoring module is further configured to compare a composite score from a first patient visit with a composite score from a subsequent patient visit to assess improvement in patient’s visual performance.

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