Devices and Methods for Novel Retinal Irradiance Distribution Modification to Improve and Restore Vision

Abstract

Devices and methods for novel retinal irradiance distribution modification (IDM) to improve, stabilize or restore vision are described herein. Also encompassed herein are devices and methods to reduce vision loss from diseases, injuries and disorders that involve damaged and/or dysfunctional and/or sensorily deprived retinal cells. Conditions that may be treated using devices and methods described herein include macular degeneration, diabetic retinopathy and glaucoma. Therapy provided by retinal IDM devices and methods described herein may also be used in combination with other therapies including, but not limited to, pharmacological, retinal laser, gene and stem cell therapies.

1 . A device, wherein the device is configured to redirect light away from a fovea or another retinal fixation region to at least two other spatially separated retinal regions, wherein the at least two other spatially separated retinal regions are different from the fovea or the another retinal fixation region, thereby to produce a retinal irradiance distribution modification (IDM). 
     
     
         2 . The device of  claim 1  wherein the device modifies in a cornea or a naturally occurring crystalline lens in one or both eyes of a subject at least one of
 i. radii of curvature, 
 ii. refractive indices, 
 iii. diffraction, 
 iv. scattering, or 
 v. any combination thereof 
 
       for light redirections away from the fovea or the another retinal fixation region to two or more other retinal regions by means of processes or devices including corneal photovitrification, corneal photodisruption, intralenticular photodisruption, corneal photoionization, corneal photoablation, photothermal keratoplasty, corneal crosslinking, conductive keratoplasty and corneal inlay or any combination thereof. 
     
     
         3 . The device of  claim 1 , comprising a laser or other light emitting source for corneal photovitrification. 
     
     
         4 . The device of  claim 1 , comprising a corneal cross-linking treatment, including an ultraviolet light source, laser thermal keratoplasty laser or corneal CPV laser or other light emitting source and photosensitizer, or other photoactivation system with photoactivation agents. 
     
     
         5 . The device of  claim 1 , comprising a laser source including at least one of a femtosecond laser, a nanosecond laser, a laser source for photodisruption, a laser source for photoionization or a laser source for photodissociation. 
     
     
         6 . The device of  claim 1 , comprising a laser source for corneal ablation. 
     
     
         7 . The device of  claim 1 , comprising a thermal corneal laser source. 
     
     
         8 . The device of  claim 1 , comprising a radiofrequency emitting device. 
     
     
         9 . The device of  claim 1 , comprising a corneal inlay for insertion in a cornea. 
     
     
         10 . The device of  claim 1 , comprising at least one of an intraocular lens (TOL), an intraocular lens accessory device (IOLAD), or any combination thereof for insertion in a phakic, aphakic or pseudophakic eye, including IOLs and IOLADs positioned in the sulcus or capsular bag, anterior chambers IOLs and IOLADs, iris-fixated IOLs and IOLADs and transscleral-sutured IOLs and IOLADs; wherein the IOL or IOLAD includes, at least one of
 i. central, paracentral or peripheral regions that are spatially separated, with or without overlapping of the regions, to modify radii of curvature, indices of refraction, diffraction, scattering or a combination thereof in any or all of the regions,   ii. two or more prisms,   iii. light-steering structures, including, but not limited to, at least one reflector within each paracentral region and at least one optical fiber, within at least one paracentral region, or   iv. any combination thereof   
       for light redirections away from the fovea or the another retinal fixation region to the at least two other spatially separated retinal regions and 
       wherein the IOL or IOLAD is configured to produce the retinal IDM of  claim 1  before insertion in the eye, or, by means of a light source, after insertion in the eye. 
     
     
         11 . The device of  claim 1 , comprising an extraocular device configured to produce the retinal IDM of  claim 1  and including spectacles and contact lenses to redirect light away from the fovea or the another retinal fixation region to the at least two other retinal regions, by means of radii of curvature, refractive indices, diffraction, scattering, light-steering structures, including, but not limited to, at least one reflector within each paracentral region and at least one optical fiber, within at least one paracentral region, or any combination thereof,
 wherein the contact lens is corneal, scleral or any combination thereof and wherein the contact lens configured for retinal IDM may be worn for retinal IDM by a subject or may be utilized for screening or customization of retinal IDM with a non-contact lens device prior to the non-contact lens device being used for retinal IDM treatment on a subject. 
 
     
     
         12 . The device of  claim 1 , wherein the IDM device is configured to produce at least one of
 i. an improvement of vision in an eye or both eyes of a subject,   ii. a stabilization of vision in an eye or both eyes of a subject,   iii. an amelioration of a visual symptom in an eye or both eyes of a subject with an ophthalmic condition, disease, injury or disorder,   iv. a reduction, compared to an untreated control group, of a rate of vision loss in an eye with a vision loss from an ophthalmic condition, disease, injury or disorder or   v. any combination thereof,   
       wherein the improved vision is for at least one of the following: visual acuity, hyperacuity, contrast sensitivity, vernier acuity, depth of focus, color vision, peripheral vision, night vision, light adaptation, dark adaptation, stereoacuity, face recognition, vision-related quality of life, or any combination thereof. 
     
     
         13 . The device of  claim 1 , configured to treat or compensate for at least one symptom of a retinal condition, disease, disorder, injury or degeneration including, but not limited, to a macular degeneration, macular scar, a macular edema, a macular hole, a macular pucker, a light-induced retinal injury, an epiretinal membrane, a retinal detachment sequela, a central serous retinopathy, a diabetic retinopathy, a retinal vascular disorder, a retinal genetic disorder, and a retinal nutritional disorder. 
     
     
         14 . The device of  claim 1 , configured to treat or compensate for at least one symptom of glaucoma or another neuro-retinal disorder. 
     
     
         15 . The device of  claim 1 , configured to treat or compensate for at least one symptom of amblyopia. 
     
     
         16 . The device of  claim 1 , wherein the IDM device is configured to produce, without requiring perceptual or oculomotor training, a natural awareness in a treatment subject of one or more alternate functional visual pathways and a natural sensorimotor learning. 
     
     
         17 . The device of  claim 1  wherein the IDM device is configured to redirect light from one or more dysfunctional areas to at least two functional areas. 
     
     
         18 . The device of  claim 1 , wherein the IDM device is further configured to
 i. decrease by at least 0.1% retinal irradiance from the field of view on spatially separated retinal areas within at least one of a foveal area or non-foveal area, and   ii. increase by at least 0.1% retinal irradiance from the field of view on at least one retinal area with viable cells, wherein the at least one retinal area is different from the foveal area or the non-foveal area of i.   
     
     
         19 . The device of  claim 18  wherein treatment with the IDM device produces in a treated eye at least one of the following: i. an increase in retinal sensitivity in a retinal region, ii. a decrease in the rate of retinal sensitivity loss compared to an untreated control group, iii. a decrease in the rate of photoreceptor loss compared to an untreated control group, iv. a decrease of the area of photoreceptor loss, v. a decrease of drusen volume, vi. a regeneration of retinal cells, vii. any combination thereof. 
     
     
         20 . A method utilizing a device, wherein the device is configured to redirect light away from a fovea or another retinal fixation region to at least two other spatially distinct retinal regions, wherein the at least two other spatially distinct retinal regions are different from the fovea or the another retinal fixation region, thereby to produce a retinal irradiance distribution modification (IDM). 
     
     
         21 . The method of  claim 20  comprising optically modifying a retinal irradiance distribution by means of light redirections from the fovea or the another retinal fixation region to the at least two other spatially distinct retinal regions,
 wherein the IDM is accomplished using 
 i. a device that produces changes in corneal or lenticular radii of curvature, refractive indices, diffraction, scattering or any combination thereof in one or both eyes of a subject by means of a process comprising at least one of corneal photovitrification, corneal photodisruption, corneal photoionization, corneal photodissociation, corneal photoablation, laser thermal keratoplasty, corneal crosslinking, or conductive keratoplasty, 
 ii. a corneal inlay or an intraocular lens configured for retinal IDM, or 
 iii. a contact lens configured for retinal IDM, or 
 iv. spectacles configured for retinal IDM, or 
 v. any combination thereof configured to produce IDM; 
 
       wherein the IDM device is configured to produce at least one of an improvement of vision in an eye or both eyes of a subject, a stabilization of vision in an eye or both eyes of a subject, an amelioration of a visual symptom in an eye or both eyes of a subject with an ophthalmic condition, disease, injury or disorder, a reduction of a rate of vision loss compared to an untreated control group in an eye or both eyes of a subject with vision loss from an ophthalmic condition, disease, injury or disorder, or any combination thereof, wherein the improved vision is for at least one of the following: visual acuity, hyperacuity, contrast sensitivity, vernier acuity, depth of focus, color vision, peripheral vision, night vision, light adaptation, dark adaptation, stereoacuity, face recognition, vision-related quality of life, or a combination thereof; and
 wherein the IDM treats or compensates for at least one symptom of a retinal degeneration. 
 
     
     
         22 . The retinal IDM method of  claim 21 , further comprising i. decreasing by at least 0.1% retinal irradiance from the field of view on spatially distinct retinal areas within at least one of a foveal area or non-foveal area, and
 ii. increasing by at least 0.1% retinal irradiance from the field of view on at least one retinal area with viable cells, wherein the at least one retinal area is different from the foveal area or the non-foveal area of i.   
     
     
         23 . The retinal IDM method of  claim 22  further comprising a retinal therapy, wherein a combination of the retinal IDM method and the retinal therapy produces in a treated eye at least one of the following: i. an increase in retinal sensitivity in a retinal region, ii. a decrease in the rate of retinal sensitivity loss compared to an untreated control group, iii. a decrease in the rate of photoreceptor loss compared to an untreated control group, iv. a decrease of the area of photoreceptor loss, v. a decrease of drusen volume, vi. a regeneration of retinal cells, or vii. any combination thereof. 
     
     
         24 . The method of  claim 23 , wherein the retinal therapy comprises introduction of a therapeutically effective amount of a vascular endothelial growth factor (VEGF) antagonist, including, but not limited to, aflibercept, ranibizumab, bevacizumab and brolucizumab, wherein the VEGF antagonist is administered via intravitreal injections, orally, topically, intraretinally, via implants or via iontophoresis and wherein the combination therapy is for treating or ameliorating a neovascular ocular disease, including macular degeneration, choroidal neovascularization and diabetic retinopathy. 
     
     
         25 . The method of  claim 23 , wherein the retinal therapy comprises sequentially administering, either before or after retinal IDM treatment, genetic, epigenetic, optogenetic or stem cell therapy for treating a retinal disorder. 
     
     
         26 . The method of  claim 23 , further comprising an additional therapy, wherein the additional therapy comprises sequentially administering topically, intraretinally, via intravitreal injections, via implants or via iontophoresis, either before or after retinal IDM treatment, a therapeutically effective amount of at least one of the following for treating glaucoma:
 i. an intraocular pressure-lowering agent, including but not limited to a miotic, an alpha or alpha/beta adrenergic agonist, a beta-blocker, a Ca 2 + channel blocker, a carbonic anhydrase inhibitor, a chlolinesterase inhibitor, a prostaglandin agonist, a prostaglandin, a prostamide, a cannabinoid, or any combination thereof;   ii. a ganglion cell-neuroprotective or neuroregenerative agent, including but not limited to a rho-kinase inhibitor, an adenosine receptor agonist or a glutamate antagonist; or   iii. any combination thereof.   
     
     
         27 . The retinal IDM method of  claim 21 , wherein the retinal degeneration comprises at least one of a macular scar, a macular edema, a macular hole, a macular pucker, an epiretinal membrane, a retinal detachment sequela, a central serous retinopathy, a diabetic retinopathy, a retinal genetic disorder, a retinal nutritional disorder, a retinal vascular disease, glaucoma, amblyopia or a combination thereof.