UV-Mask for Crosslinking Treatment of Keratoconus

Abstract

A UV-mask for treating keratoconus. The UV-mask could be made by having an image representing a surface of the patient's cornea with a topography map indicating an area of abnormal corneal thickness. The image is printed onto a sheet. The sheet is cut on or around the area of abnormal corneal thickness to create a transparent window in the sheet. The sheet is further cut on or around the corneal surface to result in a UV-mask. Also disclosed is a UV-mask for use in UV-irradiation treatment of keratoconus. Also disclosed are methods of treating keratoconus in an eye of a patient using a UV-mask.

Claims

1. A method of making a UV-mask for treating keratoconus in a patient, comprising: having an image representing a surface of the patient's cornea with a topography map indicating an area of abnormal corneal thickness; printing the image onto a sheet; cutting the sheet on or around the area of abnormal corneal thickness to create a transparent window in the sheet; cutting the sheet on or around the corneal surface to result in a UV-mask.

2. The method of claim 1, wherein the image is printed on the sheet such that the lateral width of the corneal surface is in the range of 5-12 mm.

3. The method of claim 1, wherein the resulting UV-mask has a lateral width of 9-17 mm.

4. The method of claim 1, wherein the topography map is an axial/sagittal map of the curvature of a front surface of the cornea.

5. The method of claim 1, further comprising making a deformation cut in the UV-mask.

6. The method of claim 1, further comprising making an alignment mark on the UV-mask for correctly orienting the UV-mask on the cornea.

7. The method of claim 1, wherein the sheet is paper.

8. The method of claim 7, wherein the paper has a thickness in the range of 0.05-0.2 mm.

9. The method of claim 1, wherein the UV-mask is opaque to UV light except in the transparent window.

10. The method of claim 1, wherein cutting the sheet to create a transparent window is performed by laser cutting.

11. The method of claim 1, wherein cutting the sheet on or around the corneal surface is performed by laser cutting.

12. A method of treating keratoconus in an eye of a patient using the UV-mask of claim 1, using a procedure comprising the steps of: topically applying a corneal crosslinking agent to a cornea of the eye; applying the UV-mask onto the cornea; positioning the UV-mask on the cornea such that the transparent window is over a portion of the cornea affected by keratoconus; exposing the cornea to the UV-light such that UV-light is transmitted through the transparent window, but not the opaque portion of the mask.

13. The method of claim 12, wherein the step of applying the UV-mask onto the cornea is performed after topically applying the corneal crosslinking agent to the cornea.

14. The method of claim 12, wherein visual acuity in the treated eye improves within 5 days after the procedure.

15. The method of claim 12, wherein the UV-mask has a deformation cut and, the procedure further comprises the step of deforming the UV-mask to fit the cornea.

16. The method of claim 12, wherein the UV-mask has an alignment mark, and the procedure further comprises the step of orienting the UV-mask on the cornea according to the alignment mark.

17. A method of treating keratoconus in an eye of a patient using the UV-mask of claim 1, using a procedure comprising the steps of: applying the UV-mask onto the cornea; positioning the UV-mask on the cornea such that the transparent window is over a portion of the cornea affected by keratoconus; marking on the cornea through the transparent window, an outline of an area affected by keratoconus; removing the corneal epithelium over the area of keratoconus defined by the marked outline; exposing the cornea to the UV-light.

18. The method of claim 17, wherein the step of applying the UV-mask onto the cornea is performed before topically applying the corneal crosslinking agent to the cornea.

19. The method of claim 17, wherein visual acuity in the treated eye improves within 5 days after the procedure.

20. The method of claim 17, wherein the UV-mask has a deformation cut and, the procedure further comprises the step of deforming the UV-mask to fit the cornea.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0024] FIG. 1A shows a sagittal cross-section view of an eye with a normal cornea. FIG. 1B shows an eye affected by corneal keratoconus

[0025] FIG. 2 shows a computer-generated topographic map (axial curvature) image of the eye with corneal keratoconus.

[0026] FIGS. 3A-3E show how a UV-mask is made using this map image.

[0027] FIGS. 4A-4C show how the UV-mask is used for crosslinking treatment of the cornea.

DETAILED DESCRIPTION OF AN EXAMPLE EMBODIMENT

[0028] To assist in understanding the invention, reference is made to the accompanying drawings to shown by way of illustration specific embodiments in which the invention may be practiced. The drawings herein are not necessarily made to scale or actual proportions. For example, lengths and widths of the components may be adjusted to accommodate the page size.

[0029] FIG. 1A shows a sagittal cross-section view of an eye with a normal cornea 10. Other parts of the eye seen here are the iris 12 and lens 14. The steepest part of the cornea is the apex 15. FIG. 1B shows an eye affected by corneal keratoconus. As seen here, the cornea 18 is abnormally shaped with an inferior steepening bulge. (For comparison, dotted line 16 shows the normal shape of the cornea.) The steepest part of this abnormally-shaped cornea is the apex 13, which has shifted inferiorly (downward) compared to the apex 15 of the normal cornea 10 of FIG. 1A. This invention seeks to perform cross-linking focused at the keratoconus bulge, while avoiding cross-linking on unaffected regions of the cornea 18.

[0030] FIG. 2 shows a computer-generated topographic map (axial curvature) image 20 of the eye with corneal keratoconus. The dashed line 22 represents the pupillary zone. This topographic map image 20 shows the front surface of the cornea with contour lines indicating the relative steepness of the corneal surface. Region 24 is the steepest part of the cornea, region 26 is the next steepest part, and further contour lines representing gradual concentric flattening of the cornea in the outward radial direction from region 24. These contour lines represent the area of keratoconus targeted for UV cross-linking treatment with ultraviolet (UV) light.

[0031] FIGS. 3A-3E show how a UV-mask is made using this map image 20. FIG. 3A shows the map image 20 printed onto a paper sheet 30. As printed, the size of image map 20 is reduced such that the diameter D1 measures about 8.5 mm wide. In FIG. 3B, the sheet 12 is cut along the path shown by dotted line 32 by burns made using a conventional, high precision green argon laser (such as those typically used for retinal laser treatment). As seen in FIG. 3C, when the cutout section is detached from paper sheet 30, this leaves a window 34 in paper sheet 30. This window 34 is in the shape of the area affected with keratoconus and the focus of UV-light crosslinking treatment.

[0032] With window 34 cut into the sheet 30 within map image 20, FIG. 3D shows how the UV-mask is cut out from the paper sheet 30. With burns using the green argon laser, the sheet 30 is cut along the path shown by dotted line 36 (i.e. the mask outline). The mask outline is designed such that the diameter D2 measures about 13 mm wide to fully cover the cornea. As shown in FIG. 3E, the cutout portion is detached from the sheet 30 to yield a UV-mask 40. There is also an orientation notch 42 at the top side (superior) of the UV-mask 40 to indicate the proper orientation for applying the UV-mask 40 to the eye. Using scissors, a small, radially extending cut 44 (kerf cut) is made on the superior side to allow bending, stretching, or warping of the UV-mask 40 for better fit onto the curved corneal surface. Optionally, additional kerf cuts could be made on UV-mask 40. Also, orientation markings could be made onto UV-mark 40, such as small lines or spots indicating the vertical or horizontal axes (e.g. at the 3, 6, 9, and 12 clock positions).

[0033] FIGS. 4A-4C show how the UV-mask 40 is used for crosslinking treatment of the cornea. The sclera 52 around the cornea is marked to indicates its vertical axis (0-180°) and horizontal axis (90-270°). The cornea is pretreated with riboflavin/vitamin E-TPGS (tocopheryl polyethylene-glycol succinate) and allowed to soak into the cornea for 20 minutes. Because vitamin E-TPGS functions as a permeation enhancer for riboflavin, removal of corneal epithelium (epi-off technique) is not needed. See Caruso et al, “Transepithelial Corneal Cross-Linking With Vitamin E-Enhanced Riboflavin Solution and Abbreviated, Low-Dose UV-A: 24-Month Clinical Outcomes” (February 2016) Cornea, 35(2):145-150. After the soaking, excess riboflavin-vitamin E is washed off. Alternatively, riboflavin alone could be used instead of riboflavin/vitamin E, but this requires removal of the corneal epithelium to allow penetration of riboflavin into the cornea.

[0034] FIG. 4A shows the UV-mask 40 ready for use. The UV-mask 40 is wetted with saline solution. In FIG. 4B, the UV-mask 40 is laid onto to the cornea surface with the notch 42 oriented on the superior side and positioned according to the axis markings made on the sclera 52. The position of UV-mask 40 is adjusted such that window 34 lies over the area of keratoconus targeted for crosslinking treatment. The UV-mask 40 is gently dried with a small wicking sponge. The position of UV-mask 40 should not move on the cornea. Optionally, a small dab of hydroxypropyl methylcellulose gel may be applied to the back of UV-mask 40 to enhance adhesion to the cornea.

[0035] Covered with the UV-mask 40, the cornea is then exposed to UV-A radiation for 5 minutes. The UV radiation in combination with riboflavin causes collagen fibers in the cornea to form crosslinks. The UV-mask 40 is then removed to perform another cycle of this treatment procedure. That is, riboflavin soaking, then applying the UV-mask 40, and then UV-A irradiation.

Clinical Case Examples

[0036] Case #1: A 35 year-old woman had keratoconus in both eyes and was suffering vision loss therefrom. Two years earlier, she had been treated with scleral contact lenses with some improvement. But the contact lenses became too uncomfortable for her. She continued to suffer vision loss over 18 months while wearing spectacles. Approximately a year ago, she was afflicted with Guillain-Barre syndrome, from which she had mostly recovered. In her initial eye examination, visual fields were normal.

[0037] In her pre-treatment visual acuity assessment, best spectacle-corrected distance visual acuity (BSCDVA) in her left eye (OS) was 20/200 and her resulting eyeglass prescription with best correction (Manif-Rx) was −8.75+2.75×100. Her OS maximal corneal curvature (based on the average of five measurements taken on the same day, Kmax5) was 50.3 diopters (D). A custom-made UV-mask was made and “epi-on” crosslinking was done. On post-treatment day one, her BSCDVA for OS was 20/20, and Manif-Rx −6.00+1.25×95, and Kmax5=50.0 D.

[0038] Her right eye (OD) visual acuity was BSCDVA 20/30, Manif-Rx −7.00+0.50×56, and Kmax5=52.46 D. Her right eye was treated with “epi-on” transepithelial crosslinking using a custom-made UV-mask. On post-treatment day one, her vision improved to BSCDVA 20/25+, Manif-Rx −7.50+0.50×50, and Kmax5=52.86 D. On her post-treatment day 13, her vision improved further to BSCDVA 20/20, Manif-Rx −7.25+0.50×50, and Kmax5=50.25 D

[0039] Case #2: A 56 year-old man had keratoconus in the left eye with visual acuity of BSCDVA 20/40-, Manif-Rx −5.00+2.50×15, and Kmax5=58.82 D. He was initially treated with standard epithelium-off Dresden protocol by riboflavin crosslinking. But this treatment failed to arrest keratoconus progression. His OS vision worsened to BSCDVA 20/50, Manif-Rx −4.75+5.50×15, and Kmax5=63.82 D.

[0040] Using a custom-made UV-mask, he was treated by transepithelial crosslinking with riboflavin/vitamin E-TPGS. On his post-treatment day 60, his OS vision improved to BSCDVA 20/40, Manif-Rx −5.25+3.75×10, and Kmax5=62.06 D. In addition, his right eye was also treated riboflavin/vitamin E-TPGS solution crosslinking with a custom-made UV-mask. Prior to treatment, his OD vision was 20/30-, Manif-Rx −9.00+5.50×15, and Kmax5=80.26 D. On his post-treatment day 62, his OD vision improved to BSCDVA 20/25, Manif-Rx −9.00+4.75×180, and Kmax5=75.18 D.

[0041] Case #3: A 51 year-old man had LASIK surgery 18 years ago with good results. His vision had been excellent until 2 years prior. Since then, his visual acuity had declined. He had been prescribed eyeglasses to correct his worsening astigmatism. Upon initial examination, his right eye visual acuity was BSCDVA 20/50, Manif-Rx −5.00+8.00×150, and Kmax5=80.86 D. Using a custom-made UV-mask, his right eye was treated by transepithelial crosslinking with riboflavin/vitamin E-TPGS solution. On his post-treatment day two, his OD visual acuity was improved to BSCDVA 20/40+, Manif-Rx −5.00+8.25×152, and Kmax5=79.10.

[0042] Summary: In the standard Dresden protocol, visual acuity is typically unchanged (merely stopping progression) or at best, improvements occur after months or years after the procedure. However, use of the methods described herein results far exceed those achieved by the Dresden protocol using a 9 mm UV-A beam with riboflavin crosslinking. In the above examples, there is rapid halt of disease progression and improvement in visual acuity within days to weeks.

[0043] The description and examples given herein are intended merely to illustrate the invention and are not intended to be limiting. Each of the disclosed aspects and embodiments of the invention may be considered individually or in combination with other aspects, embodiments, and variations of the invention. In addition, unless otherwise specified, the steps of the methods of the invention are not confined to any particular order of performance. Modifications of the disclosed embodiments incorporating the spirit and substance of the invention may occur to persons skilled in the art, and such modifications are within the scope of the invention.

[0044] Any use of the word “or” herein is intended to be inclusive and is equivalent to the expression “and/or,” unless the context clearly dictates otherwise. As such, for example, the expression “A or B” means A, or B, or both A and B. Similarly, for example, the expression “A, B, or C” means A, or B, or C, or any combination thereof.