Corneal Denervation for Treatment of Ocular Pain

Abstract

Methods and apparatus for the treatment of the eye to reduce pain can treat at least an outer region of the tissue so as to denervate nerves extending into the inner region and reduce the pain. For example, the cornea of the eye may comprise an inner region having an epithelial defect, and an outer portion of the cornea can be treated to reduce pain of the epithelial defect. The outer portion of the cornea can be treated to denervate nerves extending from the outer portion to the inner portion. The outer portion can be treated in many ways to denervate the nerve, for example with one or more of heat, cold or a denervating noxious substance such as capsaicin. The denervation of the nerve can be reversible, such that corneal innervation can return following treatment.

1 - 148 . (canceled) 
     
     
         149 . An apparatus to treat a cornea of an eye, the cornea having an epithelium, the apparatus comprising:
 an applicator shaped to contact the cornea to denervate nerves of an outer portion of the cornea to inhibit pain of an inner portion of the cornea.   
     
     
         150 . The apparatus of  claim 149 , wherein the applicator is configured to stun or sever the nerves to denervate the nerves of the epithelium without substantial penetration to nerves below a Bowman's membrane of the eye, or to stun nerves extending along lamella of a stroma disposed between the epithelium and an endothelium of the outer portion to denervate the inner portion. 
     
     
         151 . The apparatus of  claim 149 , wherein applicator is configured to stun the nerves with one or more of mechanical force, heat, cooling, light, photodynamic treatment, ultrasound, neurapraxia or a substance. 
     
     
         152 . The apparatus of  claim 149 , wherein the applicator is configured to sever axons of the nerves to denervate the nerves, and wherein the applicator is configured to sever the axons of nerves extending along lamella of a stroma disposed between the epithelium and an endothelium of the outer portion to denervate the inner portion, and/or wherein the applicator is configured to sever the axons disposed at a depth of no more than about 300 μm below the epithelium. 
     
     
         153 . The apparatus of  claim 149 , wherein the structure shaped to contact the epithelium comprises a structure shaped to contact a tissue region, the tissue region comprising an inner portion and an outer portion, wherein the shaped structure comprises a pain inhibiting substance and a lower side to release the pain inhibiting substance to the outer portion of the tissue region. 
     
     
         154 . The apparatus of  claim 153 , wherein the pain inhibiting substance comprises capsaicin. 
     
     
         155 . The apparatus of  claim 153 , wherein the shaped structure comprises an annulus configured to contact the tissue along an annular tissue region. 
     
     
         156 . The apparatus of  claim 153 , wherein the applicator comprises a first applicator and the shaped structure comprises an outer first pain inhibiting substance disposed on an outer portion of a lower side of the first applicator to release the pain inhibiting substance to the outer portion of the tissue region; and further comprising a second applicator comprising a structure shaped to contact at least the outer portion of the tissue region, wherein the shaped structure comprises an inner second pain inhibiting substance disposed on an inner portion of a lower side of the second applicator to release the pain inhibiting substance to the inner portion of the tissue region. 
     
     
         157 . The apparatus of  claim 149 , wherein the cornea has a region with an outer portion and an inner portion; and wherein the shaped structure is configured to conduct heat from at least the outer portion to inhibit pain. 
     
     
         158 . The apparatus of  claim 157 , wherein the shaped structure comprises a cool material configured to conduct the heat, wherein the cool material comprises an annular surface, and wherein the cool material comprises a metal. 
     
     
         159 . The apparatus of  claim 149 , wherein the shaped structure is configured for one or more of cutting, trephination, and pulsed laser cutting of the cornea. 
     
     
         160 . The apparatus of  claim 149 , wherein applicator comprises a light delivery surface and the nerves are denervated with photodynamic treatment, wherein the photodynamic treatment comprises one or more of photodynamic injury, dye uptake of the nerve, irradiation of the dye with light, or excitation of the dye with a predetermined wavelength. 
     
     
         161 . The apparatus of  claim 149 , wherein the applicator comprises a substance and the applicator is configured to apply the substance to the cornea so that the nerves are denervated with the substance, and wherein the substance comprises a calcium channel agonist, the agonist comprising one or more of capsaicin, a capsaicin analog, a capsaicinoid, dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, homocapsaicin, resinferatoxin, an agent to bind to TRPV1 protein, capsazepine, a neuropeptide depletory, or a neurostimulating agent.