Cosmetic preservatives for stabilizing human eye tissue

Keratoconus is a debilitating, progressive eye disorder characterized by weakening of the cornea and can lead to significant vision impairment or blindness. While traditional treatments required the surgical insertion of plastic corneal implants, it has been recently shown that chemically cross-linking the collagen proteins that make up the cornea can also limit progressive vision loss in keratoconus patients. However, this cross-linking procedure requires exposure to concentrated ultraviolet (UV) radiation, as well as surgical removal of the corneal epithelium, which causes significant pain and exposes the cornea to the risk of infection. This technology provides an alternative method of cross-linking collagen in the cornea by using formaldehyde releasing compounds (FARs). These compounds can penetrate into the corneal tissue without the need to remove the corneal epithelium, and do not need UV light to initiate the cross-linking process. As such, this technology provides a safer, more efficient, and more patient-friendly means of treating keratoconus and other related degenerative eye disorders.

Noninvasive, efficient, and patient-friendly treatment for keratoconus

This technology describes a family of formaldehyde releasing compounds (FARs) in current use as cosmetic preservatives, which can also be used to cross-link corneal collagen fibers. The cross-linking process stiffens the cornea, making it more resistant to the bulging, thinning, and deformation that mark keratoconus progression. FARs have the added advantage of stabilizing corneal tissue without reducing tissue transparency. Furthermore, because these compounds are small molecules, they can penetrate the corneal stroma without the need to remove the outer corneal epithelium, and can be administered topically in the form of an eyedrop. In addition to keratoconus, this technology may also be suitable for treatment of other eye disorders associated with defects in tissue collagen structure, including post-LASIK keratectasia, infectious keratitis, and progressive myopia.

These compounds’ properties as corneal collagen cross-linking agents have been demonstrated in vitro and ex vivo, and pre-clinical live animal studies are underway.

Lead Inventor:

David Paik, M.D.

Applications:

• Topical agent (e.g., eyedrops or other topical application method) for treatment of keratoconus and other disease pathologies characterized by degeneration of collagenous eye tissue (e.g. post-LASIK keratectasias)
• Topical agent for treatment of infectious keratititis
• Stabilization agent for scleral tissue to prevent axial elongation in progressive high myopia

Advantages:

• Noninvasive; no risk of surgical complications
• Does not require corneal scraping; reduced pain and risk of infection
• No unnecessary exposure to UV radiation
• Low cytotoxicity to delicate eye tissue
• Self-administrable by patients as eyedrops
• Low cost of manufacture and administration

Patent Information:

Patent Issued (US 9,125,856)

Patent Issued (US 8,466,203)

Patent Pending (WO/2015/138794)

Tech Ventures Reference: IR 2073

Related Publications:

• Kim SY, Babar N, Munteanu EL, Takaoka A, Zyablitskaya M, Nagasaki T, Trokel SL, Paik DC. “Evaluating the toxicity/fixation balance for corneal cross-linking with sodium hydroxymethylglycinate (SMG) and riboflavin-UVA (CXL) in an ex vivo rabbit model using confocal laser scanning fluorescence microscopy” Cornea. 2016 Apr; 35(4): 550-6.

• Babar N, Kim M, Cao K, Shimizu Y, Takaoka A, Trokel SL, Paik DC. “Cosmetic preservatives as therapeutic corneal and scleral tissue cross-linking (TXL) agents. Invest Ophthalmol Vis Sci. 2015 Jan; 56(2): 1274-82.

• Kim MJ, Takaoka A, Hoang QV, Trokel SL, Paik DC. “Pharmacologic alternatives to riboflavin photochemical corneal cross-linking: a comparison study of cell toxicity thresholds” Invest Ophthalmol Vis Sci. 2014 Apr; 55: 3247-57.

• ¬Wen Q, Trokel SL, Kim M, Paik DC. “Aliphatic β-nitroalcohols for therapeutic corneoscleral cross-linking: corneal permeability considerations” Cornea. 2013 Feb;32(2):179-84.

• Paik DC, Solomon MR, Wen Q, Turro NJ, Trokel SL. “Aliphatic beta-nitroalcohols for therapeutic corneoscleral cross-linking: chemical mechanisms and higher order nitroalcohols” Invest Ophthalmol Vis Sci. 2010 Feb;51(2):836-43.

• Paik DC, Wen Q, Airiani S, Braunstein RE, Trokel SL. “Aliphatic beta-nitro alcohols for non-enzymatic collagen cross-linking of scleral tissue” Exp Eye Res. 2008 Sep;87(3):279-85.