Granted Patent B2

US 12,442,827 · App. 17/775,040 · Granted Oct 14, 2025

Inventor: Dimitrios Karamichos (Carrollton, TX)

Assignees: UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER AT FORT WORTH; THE BOARD OF REGENTS OF THE UNIVERSITY OF OKLAHOMA

G01N33/76G01N2333/59G01N2800/04

Abstract

Claims (31)

1. A method for treating a disease or condition of the eye related to a ratio of luteinizing hormone to follicle-stimulating hormone (LH/FSH ratio) comprising:

obtaining or having obtained a biological sample from a subject;

determining the LH/FSH ratio in the biological sample, wherein a decrease in the LH/FSH ratio when compared to an age-matched subject that does not have a disease or condition of the eye related to an LH/FSH ratio is indicative of a current or future disease or condition of the eye related to an LH/FSH ratio in the subject;

and administering to the subject with a decrease in the LH/FSH ratio an effective amount of gonadotropes, pituitary hormones, Gonadotropin-releasing hormones, LH, FSH, dehydroepiandrosterone sulfate (DHEA-S), Estrone, Estriol, or sex hormones, with a Prolactin-Inducible Protein (PIP) or a Gonadotropin-releasing hormone (GNRH) in an amount sufficient to increase the LH/FSH ratio.

2. The method of claim 1 , wherein the disease or condition of the eye is Keratoconus; or is Keratoconus and a severity of Keratoconus is determined by measuring a decrease in the LH/FSH ratio for Keratoconus levels KC-1, KC-2, KC-3 and KC-4.

3. The method of claim 1 , wherein a first biological sample is obtained at a first time that is before, during, or after puberty, and a second biological sample is obtained at a second time after the first time, wherein a decrease in the LH/FSH ratio between the first and second time is predictive of Keratoconus when the second sample is obtained prior to symptoms of Keratoconus.

4. The method of claim 1 , wherein the biological sample is a blood, plasma, tear, intravitreal, blood-serum, hair, urine, aqueous humor, saliva or sweat sample.

5. The method of claim 1 , further comprising detecting at least one of dehydroepiandrosterone (DHEA) or dehydroepiandrosterone sulfate (DHEA-S) in the biological sample, wherein an increase in DHEA or DHEA-S when compared to an age-matched subject is indicative of Keratoconus; or further comprising detecting in the biological sample at least one of estrone, estriol, or gonadotropin-releasing hormone, wherein a decrease of estrone, estriol, gonadotropin-releasing hormone, or combinations thereof when compared to an age-matched subject, is indicative of Keratoconus.

6. A method of treating a subject that will develop a disease or condition of the eye related to a ratio of luteinizing hormone to follicle-stimulating hormone (LH/FSH ratio) comprising:

obtaining or having obtained a biological sample from the subject;

determining a level of expression of LH and FSH in the biological sample;

calculating the LH/FSH ratio in the biological sample;

determining if there is a decrease in the LH/FSH ratio when compared to an age-matched subject that does not have a disease or condition of the eye related to an LH/FSH ratio, wherein a decrease in the LH/FSH ratio is indicative of a current or future disease or condition of the eye related to an LH/FSH ratio in need of treatment; and

administering to the subject with a decrease in the LH/FSH ratio an effective amount of gonadotropes, pituitary hormones, Gonadotropin-releasing hormones, LH, FSH, dehydroepiandrosterone sulfate (DHEA-S), Estrone, Estriol, or sex hormones, with a Prolactin-Inducible Protein (PIP) or a Gonadotropin-releasing hormone (GNRH) in an amount sufficient to increase the LH/FSH ratio.

7. The method of claim 6 , wherein the disease or condition of the eye is Keratoconus; or is Keratoconus and a severity of Keratoconus is determined by measuring a decrease in the LH/FSH ratio for Keratoconus levels KC-1, KC-2, KC-3 and KC-4.

8. The method of claim 6 , wherein a first biological sample is obtained at a first time that is before, during, or after puberty, and a second biological sample is obtained at a second time after the first time, wherein a decrease in the ratio of LH/FSH between the first and second time is predictive of Keratoconus, and the second sample is obtained prior to symptoms of Keratoconus.

9. The method of claim 6 , wherein the biological sample is a blood, plasma, tear, intravitreal, blood-serum, hair, urine, aqueous humor, saliva or sweat sample.

10. The method of claim 6 , further comprising detecting at least one of dehydroepiandrosterone (DHEA) or dehydroepiandrosterone sulfate (DHEA-S) in the biological sample, wherein an increase in DHEA or DHEA-S when compared to an age-matched subject is indicative of Keratoconus; or further comprising detecting in the biological sample at least one of estrone, estriol, or gonadotropin-releasing hormone, wherein a decrease of estrone, estriol, gonadotropin-releasing hormone, or combinations thereof when compared to an age-matched subject, is indicative of Keratoconus.

11. The method of claim 6 , wherein an amount of a Prolactin-Inducible Protein (PIP) effective to treat the disease or condition of the eye is administered to the subject.

12. A method for treating a patient with a disease or condition of the eye related to a ratio of luteinizing hormone to follicle-stimulating hormone (LH/FSH ratio), the method comprising the steps of:

performing or having performed a determination of the LH/FSH ratio in a biological sample obtained from a patient suspected of having a disease or condition of the eye related to an LH/FSH ratio; and

administering to the subject with a decrease in the LH/FSH ratio as compared to an age-matched control that does not have a disease or condition of the eye related to an LH/FSH ratio, an effective amount of gonadotropes, pituitary hormones, Gonadotropin-releasing hormones, LH, FSH, dehydroepiandrosterone sulfate (DHEA-S), Estrone, Estriol, or sex hormones, with a Prolactin-Inducible Protein (PIP) or a Gonadotropin-releasing hormone (GNRH) in an amount sufficient to increase the LH/FSH ratio.

13. The method of claim 12 , wherein the PIP is provided in an amount of 0.1 ng/ml to 1 mg/ml or the GNRH is provided in an amount of 0.1 pg/ml to 1 mg/ml.

14. The method of claim 12 , wherein the disease or condition of the eye is Keratoconus; or is Keratoconus and a severity of Keratoconus is determined by measuring a decrease in the LH/FSH ratio for Keratoconus levels KC-1, KC-2, KC-3 and KC-4.

15. A method of treating a patient with Keratoconus comprising:

obtaining a sample of corneal stromal cells from a patient suspected of having Keratoconus;

determining a level of expression of luteinizing hormone receptor (LHR), follicle stimulating hormone receptor (FSHR), or both in the sample, wherein an increase in LHR, or a decrease of FHSR, or both as compared to an age matched subject that does not have keratoconus, is indicative of Keratoconus; and

administering to the patient with Keratoconus a composition comprising an effective amount of gonadotropes, pituitary hormones, Gonadotropin-releasing hormones, LH, FSH, dehydroepiandrosterone sulfate (DHEA-S), Estrone, Estriol, or sex hormones, and a Prolactin-Inducible Protein (PIP) or a Gonadotropin-releasing hormone (GNRH) in an amount sufficient to increase an LH/FSH ratio in the patient.

16. The method of claim 15 , wherein the PIP is provided in an amount of 0.1 ng/ml to mg/ml or the GNRH is provided in an amount of 0.1 pg/ml to 1 mg/ml.

17. The method of claim 15 , wherein the composition is formulated for topical, or ophthalmic.

18. The method of claim 17 , wherein the composition is delivered into the conjunctival sac of the patient or administered to the patient by intravitreal, subconjunctival, retrobulbar, intracameral, or sub-Tenon's administration.

Assignments (3)

Continuity (2)

References Cited (37)