CA2800186A1 - Nutritional formulations and method for treating diseases - Google Patents
Nutritional formulations and method for treating diseases Download PDFInfo
- Publication number
- CA2800186A1 CA2800186A1 CA2800186A CA2800186A CA2800186A1 CA 2800186 A1 CA2800186 A1 CA 2800186A1 CA 2800186 A CA2800186 A CA 2800186A CA 2800186 A CA2800186 A CA 2800186A CA 2800186 A1 CA2800186 A1 CA 2800186A1
- Authority
- CA
- Canada
- Prior art keywords
- lutein
- subject
- zeaxanthin
- retinal
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Ophthalmology & Optometry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The present invention provides methods for treating retinal disorders using a nutraceutical composition comprising lutein and zeaxanthin. Methods for treating vitreomacular traction disorder and related disorders are disclosed.
Description
Blakes Ref. 78863/00001 3 [0001] Not applicable.
[0002] The field of invention relates to methods and compositions useful for treating retinal 6 disorders in a subject including vitreomacular traction and related disorders.
8 [0003] Vitreomacular traction (VMT) is an idiopathic disorder, wherein the vitreous gel 9 strongly adheres to the retina. With ageing, it is common for the vitreous to separate from the retina. However, if separation is incomplete, the retina is pulled by the vitreous. This "traction"
11 force generated by vitreal pulling on the retina can cause edema within the retina, vessel 12 damage, bleeding, optic nerve damage, retinal distortion and decreased visual acuity (VA).
13 Adhesion size and strength of the traction force determine the resulting ocular pathology and 14 symptoms. Continuous VMT may induce retinal lesions, leading to VMT
syndrome.
Complications related to VMT syndrome include, but are not limited to, epiretinal membrane 16 (ERM), macular pucker, partial lamellar holes, macular holes, visual impairment and blindness.
17 [0004] Some VMT disorders are asymptomatic. Treatment for asymptomatic VMT involves 18 regular monitoring of the patient for further progression of VMT. In cases where VMT causes 19 reduced or distorted vision in a patient, the current standard of care is pars plana vitrectomy.
Vitrectomy requires surgical removal of the vitreous from the eye and membrane peeling to 21 relieve epiretinal traction. Complications of vitrectomy can include retinal tearing or detachment, 22 endopthalmitis and postoperative cataracts and fibrovascular membranes.
23 [0005] On October 17, 2012 the United States Food and Drug Administration (FDA) 24 approved a biological agent for treatment of VMT called Jetrea TM
(ocriplasmin;
ThromboGenics). Ocriplasmin, a proteolytic enzyme that cleaves fibronectin, laminin and 26 collagen, is to be provided to a patient by intravitreal injection to resolve vitreomacular adhesion, 27 which can result in VMT. Ocriplasmin does not reverse fibrosis.
28 [0006] Less invasive methods of treating symptomatic VMT are desirable.
22313576.1 1 Blakes Ref. 78863/00001 1 [0007] Nutrition is one feature of ocular health that has been studied in age-related ocular 2 diseases such as age-related macular degeneration (AMD). Macular degeneration is a chronic 3 eye disease that causes vision loss in the central field of vision. Dry macular degeneration is 4 marked by deterioration of the deep layers of the retina. Wet macular degeneration is characterized by blood vessels that grow under the retina, leaking blood and fluid. The 6 pathology of AMD is believed to be caused, at least in part, by oxidative damage (Beatty et al., 7 Surv. Opthamol. 2000,45:115-134; Cal et al., Prog. Retin. Eye Res. 2000, 29:263-271, 8 incorporated herein by reference as if set forth in their entirety). The healthy eye contains 9 antioxidant molecules, including enzymes, vitamins C and E, omega-3 fatty acid docosahexanic acid (DHA) and macular pigments lutein and zeaxanthin. Deficiency of antioxidants in the 'II ageing eye is believed to be a risk factor for development of AMD
(Ocular Nutrition: It's Role in 12 Maintaining Eye Health, Module 1: Nutrition and Health of the Aging Eye,2011, 6 pages, 13 incorporated herein by reference as if set forth in its entirety). It follows that nutrient 14 supplements, including antioxidants such as, zinc, vitamin C, vitamin E, beta carotene, lutein, zeaxanthin and omega-3 fatty acids, are sometimes recommended to prevent AMD
progression 16 and improve vision.
17 [0008] Lutein and zeaxanthin are xanthophyll carotenoid pigments found in the macula.
18 Subjects having AMD are known to have decreased amounts of lutein and zeaxanthin in their 19 macula. Some studies suggest that visual acuity, contrast sensitivity, and the amount of macular pigment in the human eye can be improved as a result of lutein and zeaxanthin supplementation 21 or a combination of these xanthophylls with other antioxidants (Stiles et al. (2004) Optometry, 22 75:216-230, incorporated herein by reference as if set forth in its entirety). Other studies 23 suggest that macular pigment optical density (MPOD), a measure of the amounts of lutein and 24 zeaxanthin in the macula of the living human eye, is a marker of the health of the human eye (U.S. Patent Application Publication No. 2012/0070422, incorporated herein by reference as if 26 set forth in its entirety).
27 [0009] Nutritional supplements including lutein and zeaxanthin have also been suggested to 28 promote ocular health and treat "ocular diseases" (see, for example, U.S. Patent Application 29 Publication Nos. 2010/0068298 and 2012/0258168, each incorporated herein by reference as if set forth in their entirety). However, the range of "ocular diseases" appears to be limited to AMD
31 and related ocular disorders thought to be associated with oxidative stress (U.S. Patent 32 Application Publication No. 2010/0068298). Similarly, "ocular health" is thought to decrease 33 naturally with age, and can be compromised by oxidative stress, illness and visual stresses, 22313576.1 2 Blakes Ref. 78863/00001 1 such as prolonged exposure to visual display monitors (U.S. Patent Application Publication No 2 2012/0258168). Vitreomacular traction has not been considered in such studies of treating 3 "ocular disease" or "ocular health".
4 [0010] Nutritional treatment of VMT has not been suggested in the literature or established in the field, but is desirable as a non-invasive alternative to treatment with vitrectomy or 6 intravitreal injections.
8 [0011] In one aspect, the present invention provides use of a composition comprising lutein 9 and zeaxanthin for treatment of a retinal disorder. In an embodiment of the aspect, the use comprises administering to a subject in need thereof a therapeutically effective amount of the 11 composition comprising lutein and zeaxanthin.
12 [0012] In some embodiments of the aspect the retinal disorder is vitreomacular traction 13 disorder. In some embodiments of the aspect the retinal disorder is a nutritional deficiency 14 disorder.
[0013] In some embodiments of the aspect the therapeutically effective amount of lutein is 16 about 10-20mg daily. In some embodiments of the aspect the therapeutically effective amount 17 of zeaxanthin is about 0.5-5 mg daily. In some embodiments of the aspect 20mg lutein and 18 5mg zeaxanthin are administered to the subject daily.
19 [0014] In some embodiments, the composition is administered orally to the subject. In some embodiments, the composition is administered daily for two to 24 months.
21 [0015] In some embodiments, the composition further comprises at least one of omega 3 22 fatty acids and probiotics. In some embodiments fatty acids are at least one of 23 Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA). In some embodiments the 24 probiotics are live microorganisms belonging to the order Lactobacilliales or the genus Bifidobacterium.
27 [0016] The features of the invention will become more apparent in the following detailed 28 description in which reference is made to the appended drawings wherein:
22313576.1 3 Blakes Ref. 78863/00001 1 [0017] FIGS. 1A-H depict ocular photos obtained from the subject of case 1. A: OD, 2 October, 2009; B: OS, October, 2009; C: OD, November, 2010; D: OS, November, 2010; E: OD, 3 November, 2011; F: OS, November, 2011; G: OD, May, 2012; and H: OS, May, 2012.
4 [0018] FIG. 2 depicts changes in retinal lesion size in the subject of case 1. Changes in retinal lesion size are indicated on the Y axis, treatment and time are indicated on the x axis.
6 L(20)Z(0) on the Y axis refers to administration of 20 mg lutein every other day. All other 7 treatments were administered on a daily basis.
8 [0019] FIGS. 3A-D depict ocular photos obtained from the subject of case. A: OD, October 9 12, 2012; B: OS, October 12, 2012; C: OD, November 15, 2012; D: OS, November 15, 2012.
[0020] FIGS. 4A-F depict ocular photos obtained from the subject of case 19. A: OD, 11 September 2009; B: OS, September 2009; C: OD, September 2010; D: OS, September 2010;
12 E: OD, April 2012; F: OS, April 2012.
13 [0021] FIGS. 5 A-D depict ocular photos obtained from the subject of case 38. A: OD, 14 January 2012; B: OS, January 2012; C: OD, July 2012; D: OS, July 2012.
[0022] FIGS. 6 A-D depict ocular photos obtained from the subject of case 41. A: OD, 16 October, 2012; B: OS, October, 2012; C: OD, November, 2012; and D: OS, November, 2012.
18 [0023] The present invention is based upon the inventor's observation that vitreomacular 19 traction (VMT) can be treated in subjects, in need thereof, by daily administration of a composition comprising lutein and zeaxanthin. A portion of the inventor's observations were 21 presented by the inventor at a meeting of The American Academy of Optometry, Ocular 22 Nutrition Special Interest Group, on Wednesday, October 24, 2012, and by another who is not 23 an inventor of the present invention at the same meeting on the same date.
24 [0024] The definitions of certain terms as used in this specification are provided below.
Unless defined otherwise, all technical and scientific terms used herein generally have the same 26 meaning as commonly understood by one of ordinary skill in the art to which this invention 27 belongs.
28 [0025] As used herein, the term "about" will be understood by persons of ordinary skill in the 29 art and will vary to some extent depending upon the context in which it is used. If there are uses 2313576.1 4 Blakes Ref. 78863/00001 1 of the term which are not clear to persons of ordinary skill in the art, given the context in which it 2 is used, "about" will mean up to plus or minus 10% of the enumerated value.
3 [0026] As used herein, the "administration" of an agent to a subject includes any route of 4 introducing or delivering to a subject a compound to perform its intended function.
Administration can be carried out by any suitable route, including orally, intraocularly, 6 intranasally, or topically. Administration includes self-administration and the administration by 7 another.
8 [0027] As used herein the term "probiotic" refers to live microorganisms that may confer a 9 health benefit on their host. Probiotics can be consumed as part of fermented foods or as dietary supplements. Examples of probiotic organisms include some members of the Order 11 Lactobacillales, such as Lactobacillus spp. And members of the genus Bifidobacterium.
12 [0028] As used herein, the term "nutraceutical" refers to specific chemical compounds found 13 in foods that can prevent disease or ameliorate an undesirable condition.
14 [0029] As used herein, the term "retinal disorder" or "disorder of the retina" refers to any impairment of normal physiological function of the retina.
16 [0030] As used herein, the term "nutritional deficiency disorder"
refers to an impairment of 17 normal physiological function of the retina, wherein the cause of impairment is the lack of one or 18 more nutrients.
19 [0031] As used herein, the term "Oculus Dexter' or "OD" refers to the right eye of a subject.
[0032] As used herein, the term "Oculus Sinister" or "OD" refers to the left eye of a subject.
21 [0033] As used herein, the term "omega 3 fatty acids" refers to fats commonly found in 22 marine and plant oils, such as fish oils, algal oil, squid oil, echium oil and flaxseed oil. Examples 23 of omega 3 fatty acids useful in the present invention include, but are not limited to, 24 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
[0034] As used herein, the term "therapeutically effective amount" refers to a quantity 26 sufficient to achieve a desired therapeutic and/or prophylactic effect, e.g., an amount which 27 results in the prevention of, or a decrease in, the symptoms associated with a retinal disorder.
28 For example, a "therapeutically effective amount" of the composition of the present invention 29 refers to levels of the composition that, when administered to the subject on a daily basis, 22313576.1 5 Blakes Ref. 78863/00001 1 ameliorate, in part or in full, at least one symptom of the disorder, for example, the size of a 2 retinal lesion.
3 [0035] As used herein, the term "lesion" refers to a localized change in an organ or tissue of 4 the body. "Retinal lesions", referred to herein, can be characterized by at least one of puckering, fibrosis, lamellar splitting, and/or dragging, swelling, bulging of retinal tissues and 6 retinal holes.
7 [0036] As used herein, the terms "treating" or "treatment" or "alleviation" refers to both 8 therapeutic treatment and prophylactic or preventative measures, wherein the object is to 9 reverse, prevent or slow down (lessen) the targeted pathologic condition or disorder. A subject is successfully "treated" for a retinal disorder if, after receiving an effective therapeutic amount 11 of the composition according to the methods described herein, the subject shows measurable 12 reduction in at least one symptom or sign of a retinal disorder. It is also to be appreciated that 13 the various modes of treatment or prevention of medical conditions as described are intended to 14 mean "substantial", which includes total but also less than total treatment or prevention, and wherein some biologically or medically relevant result is achieved.
16 [0037] As used herein, the terms "vitreomacular traction,"
"vitreomacular traction disorder"
17 and "vitreoretinal traction" refer to a conditions wherein the vitreous gel of the human eye 18 adheres to the retina, causing pulling, or "traction", forces on the retina that can cause ocular 19 damage.
[0038] As used herein, the terms "units of diameter" and units made in reference to lesion 21 size or diameter refer to units of diameter of the posterior pole of an eye, which measures ten 22 units in diameter between the vascular arcades. A lesion can be larger than 19 units.
23 [0039] The terms "comprise", "comprises", "comprised" or "comprising"
may be used in the 24 present description. As used herein (including the specification and/or the claims), these terms are to be interpreted as specifying the presence of the stated features, integers, steps or 26 components, but not as precluding the presence of one or more other feature, integer, step, 27 component or a group thereof as would be apparent to persons having ordinary skill in the 28 relevant art.
29 [0040] Non-invasive methods for treating vitreomacular traction (VMT) and related disorders have been highly desired. The present invention provides methods for treating VMT using a 22313576.1 6 Blakes Ref. 78863/00001 1 nutraceutical composition. A person of skill in the art understands that nutraceutical compounds 2 are found in foods and can be used to prevent disease or ameliorate an undesirable condition.
3 [0041] In some embodiments of the present invention, the methods involve identifying a 4 subject in need of VMT treatment and administering to the subject a therapeutically effective daily dose of a composition comprising lutein and zeaxanthin.
6 [0042] Subjects in need of VMT treatment typically have a retinal lesion in one or both eyes.
7 Retinal lesions can be detected using methods known to those of skill in the art, at least for 8 example, retinal photography, optical coherence tomography, OCT, visual acuity, Amsler grid or 9 fundus examination [0043] In one embodiment of the present invention, therapeutically effective dosages of 11 lutein and zeaxanthin for treatment of VMT include about 10-20mg lutein and about 0.5-5mg 12 zeaxanthin. Preferably, a ratio of 4:1 lutein: zeaxanthin is provided to a subject for treatment of 13 VMT. An especially preferred therapeutically effective daily dose of a composition comprising 14 lutein and zeaxanthin comprises 20mg lutein and 5mg zeaxanthin.
[0044] In some embodiments of the present invention, the composition is administered to 16 the subject orally. The compositions of the invention can be formulated with suitable carriers 17 such as starch, sucrose or lactose in tablets, capsules, solutions, powders, syrups and 18 emulsions, or oils. Suitable optional carriers include but are not limited to, for example, fatty 19 acids, esters and salts thereof, that can be derived from any source, such as for example, natural or synthetic oils, fats, waxes or combinations thereof. In preferred embodiments of the 21 present invention, the source of the fatty acids is DHA or EPA, which may be provided in 22 combination with the composition or separately.
23 [0045] In some embodiments of the present invention, the composition is administered daily 24 for two to 24 months to the subject. In preferred embodiments, the composition is administered daily to the subject for 3 months. In particularly preferred embodiments of the present invention, 26 the composition is administered to the subject daily until retinal lesions are ameliorated 27 completely.
28 [0046] In one embodiment of the present invention, the method is used for treating VMT. In 29 other embodiments of the present invention, the method is used for treating retinal disorders related to VMT, such as, for example, epiretinal membrane (ERM), macular pucker, partial 31 lamellar holes and/or macular holes.
22313576.1 7 Blakes Ref. 78863/00001 1 [0047] It is contemplated herein, that idiopathic VMT and related retinal disorders are 2 associated with an underlying nutritional deficiency disorder, wherein the subject having the 3 disorder is deficient in at least lutein and zeaxanthin. It is further contemplated that such 4 nutritional deficiency can be corrected in a subject in need of VMT
treatment by administering to the subject therapeutically effective amounts of lutein and zeaxanthin, daily.
6 [0048] It is contemplated herein that treatment of VMT with lutein and zeaxanthin can be 7 further improved by administering to the subject one or more omega 3 fatty acid and/or 8 probiotic.
9 [0049] EXAMPLES
[0050] The present invention is further illustrated by the following examples, which should 11 not be construed as limiting in any way.
12 [0051] Example 1: Materials and Methods 13 [0052] Diagnosis of vitreomacular traction (VMT): VMT can be symptomatic or 14 asymptomatic. Complaints of reduced or distorted vision may or may not be reported by the subject. Measurement of visual acuity (VA) may or may not be normal or reduced in one or both 16 eyes. Measurement for distortion on an Amsler grid may or may not show distortion in one or 17 both eyes. Retinal photography may show signs of VMT in the original color composite image 18 (e.g., upper left photo in four panel photo of FIG. 1A). Further analysis of the choroid (e.g., 19 upper right photo in four panel photo of FIG. 1A), the retina (e.g., lower left photo in four panel photo of FIG. 1A), and the retinal nerve fibre layer (RNFL) (e.g., lower right photo in four panel 21 photo of FIG. 1A), may reveal puckering, fibrosis, lamellar splitting, partial lamellar holes, 22 pseudo macular holes, bulging and/or edema in the choroid, retinal and/or RNFL images.
23 Further analysis with "3-D" images of the choroid, retina and RNFL
layers may show elevations 24 diagnostic of VMT, such as, for example, the presence, severity and/or size of puckering, partial lamellar holes, macular holes, bulging or edema. Further, "3-D" images can be useful for 26 determining which layers of the eye tissue are affected by VMT.
27 [0053] Ocular imaging: retinal photographs were taken using a Canon CR-1 Digital Retinal 28 Camera and analyzed using EyeScape Digital Imaging Software, version 7.5.5.
29 [0054] The settings used for taking retinal photographs were such that optimal contrast and brightness for each subject was achieved. Most retinal photographs were taken with a dilated 22313576.1 8 Blakes Ref. 78863/00001 1 pupil. Some subjects have naturally very large pupils. In these cases, pupil dilation may not 2 have been required to obtain sufficient images. The Canon CR-1 has a setting for small pupils 3 that was used as required.
4 [0055] Example 2: Case 1.
[0056] Subject Description: The subject is a male born in 1938. Subject underwent laser 6 therapy for retinal detachment in his left eye in 2002. An ophthalmological examination in 7 December 2008 revealed ERM in the subject's OS.
8 [0057] Treatment: Subject began administration of 20 mg lutein every second day in June 9 2009 and continued for 4 months. From October 2009 through October 2010 the subject was administered 3 times daily, 1000 mg omega-3 fatty acids from fish oil. From November 2010 11 through November 2011 the subject was administered daily with 10 mg lutein and 2.0 mg 12 zeaxanthin. From December 2011 through October 2012, the subject was administered daily 13 with 20 mg lutein and 5 mg zeaxanthin.
14 [0058] Results: Four months of treatment with lutein (10 mg) every other day resulted in reduction of ERM OD from 1.5 units to 0.5 units and a reduction of OS macular pucker from 6.5 16 units to 5.0 units (FIG. 1, A, B). During the following 12 months, in the absence of supplemental 17 lutein and zeaxanthin, lesions in the subject's right and left eyes increased (FIG. 2). The 18 subject's ERM OD increased from 0.5 units to 4.5 units and OS macular pucker increased from 19 5 units to 8 units (FIGS. 1C and 1D relative to 1A and 16, respectively). From November 2010 through November 2011, treatment with 10 mg lutein and 2.0 mg zeaxanthin, resulted in a 21 decrease in retinal lesion size in both of the subject's eyes (FIG. 2).
The subject's ERM OD
22 decreased from 4.5 units to 2 units and OS macular pucker decreased from 8 units to 4 units 23 (FIGS. lE and 1F relative to FIGS. 1C and 1D, respectively). Further treatment with an 24 increased dose of lutein (20 mg/day) and zeaxanthin (5 mg/day) for 11 months resulted in further decrease in retinal lesion size (FIGS. 1G and 1H relative to FIGS. 1E
and 1F, 26 respectively). Treatment with 20 mg/day lutein and 5 mg/day zeaxanthin was sufficient to 27 completely ameliorate the lesion in the subject's left eye.
28 [0059] Example 3: Case 16.
29 [0060] Subject Description: The subject is a female born in 1949.
Subject had normal retinal health in December, 2010. April 2012, the subject had ERM OS of 13.5. October 12, 2012, 31 subject had lesions in both eyes, OD 11.5 units, OS 14.5 units.
2231.3576.1 9 Blakes Ref. 78863/00001 1 [0061] Treatment: The subject was administered 20 mg/day lutein and 5 mg/day 2 zeaxanthin on an irregular basis from April 2012 until October 11, 2012.
The subject was 3 administered daily 20 mg lutein and 5 mg zeaxanthin from October 12, 2012 through November 4 15,2012.
[0062] Results: Following about one month of regular administration of lutein and 6 zeaxanthin, the subject's lesion size and severity decreased in both eyes: OD lesion decreased 7 from 11.5 to 10 units, the OS lesion decreased from 14.5 to 9.5 units.
8 [0063] Example 4: Case 19.
9 [0064] Subject Description: The subject is a male born in 1941.
Subject had OD lesion of 0.5 units in September 2009. January 2010, the subject had OD and OS lesions of 0.5 units.
11 Further, the subject has been diagnosed with diabetes in January 2010 and was being treated 12 with metformin. September 2010, subject had no OD lesion and an OS
lesion of 7.5 units.
13 October 2011, subject's OS lesion had increased to 8.5 units. By December 2011, the subject 14 was no longer diabetic and was no longer taking metformin. April 2012, subjects' OS lesion had decreased to 0.5 units. October 2012, subject's OS lesion had been ameliorated 16 [0065] Treatment: The subject was administered 10 mg lutein and 2.0 mg zeaxanthin daily 17 from October 2010 until October 2011. The subject was administered 20 mg lutein and 5 mg 18 zeaxanthin daily from November 2011 through October, 2012.
19 [0066] Results: Twelve months of treatment with lutein (10 mg) and zeaxanthin (2.0 mg) resulted in an increase in OS lesion size from 7.5 units to 8.5 units (FIG. 3, C, D). Further 21 treatment with an increased dose of lutein (20 mg/day) and zeaxanthin (5 mg/day) for 6 months 22 was sufficient to completely ameliorate the OS lesion (FIG. 3F).
23 [0067] Example 5: Case 38.
24 [0068] Subject Description: The subject is a female born in 1946. The subject is diabetic.
Subject had ERM OS lesion of 4.3 units in January 2010. OS lesion had increased to 8 units by 26 January 2012. July 2012, subject's ERM OS lesion had been ameliorated.
27 [0069] Treatment: The subject was administered 20 mg lutein and 5 mg zeaxanthin daily 28 from January 2012 through July 2012.
22313576.1 10 Blakes Ref. 78863/00001 1 [0070] Results: Six months of treatment with lutein (20 mg/day) and zeaxanthin (5 mg/day) 2 was sufficient to completely ameliorate the ERM OS lesion in the subject (FIG. 5D).
3 [0071] Example 6: Case 41.
4 [0072] Subject Description: The subject is a male born in 1970.
Subject developed central serous retinopathy in both eyes, September 17, 2012. OS became symptomatic with VA 20/40 6 and large area of "bulging lines" on Amsler grid. Subject's OD lesion was 4 units and OS lesion 7 was 6 units on October 18, 2012. Subjects OD lesion was 4 units, but improving on November 8 30, 2012 and subject's OS lesion had been ameliorated by the same date;
OS VA 20/20, 9 Amsler grid greatly improved relative to October 18, 2012 measurement.
[0073] Treatment: The subject was administered 10 mg lutein and 2.0 mg zeaxanthin daily 11 for one week commencing on October 11, 2012. At this time the subject was also administered 12 daily with 360mg EPA and 240 mg DHA. The subject was administered no lutein or zeaxanthin 13 from October 18 through October 24, 2012, at which time the subject was administered daily 14 probiotics containing 5 billion live microorganism cells. From October 25, 2012 through November 30, 2012 the subject was administered daily with 20 mg lutein, 5 mg zeaxanthin, 16 360mg EPA, 240 mg DHA and probiotics containing 5 billion live microorganism cells.
17 [0074] Results: Within 6 weeks following treatment with lutein (20mg/day) zeaxanthin (5 18 mg/day), probiotics and omega 3 fatty acids the subject's OS VA returned to 20/20 and the 19 subject's Amsler distortion was greatly diminished. Further, treatment was sufficient to ameliorate the subject's OS lesion (FIG. 6D relative to FIG. 6B).
21 [0075] Example 7: Lutein and zeaxanthin dosage response trials indicate positive results for 22 treatment of VMT, including retinal lesions.
23 [0076] Subject Description: Data were collected from 40 subjects having symptomatic VMT
24 over a period of 4.5 years.
[0077] Treatment: Subjects were treated daily with lutein and zeaxanthin as described in 26 table 1.
27 [0078] Table 1: Raw data collected from subjects during preliminary lutein zeaxanthin trial.
28 Plh indicates partial lamellar hole. Pucker (macular) is described based on a qualitative score of 22313576.1 11 Blakes Ref. 78863/00001 mild to severe, wherein a score of 1of 3 is a mild pucker, a score of 2 of 3 is a moderate pucker 2 and a score of 3 of 3 is a sever pucker.
Case # Gender Date of Date of Ocular Lutein (mg) Zeaxanthin (mg) OD lesion OS lesion Birth Examination , (units) , (units) 1 M 1939 Jul-08 0 0 1.5 6 Oct-09 10 0 0.5 5 Nov-10 0 0 4.5, 8 Nov-11 10 2 2 4 May-12 20 5 .5 0 , Oct-12 20 5 0.5 0 _ 2 F 1959 Apr-09 0 0 0 8.5 _ Nov-10 20 0 0 3 -Mar-12 20 5 0 _ 0 Sep-12 0 0 1 0.5 3 M 1959 Apr-09 0 0 9 0 May-10 0 0 9 0 Jun-11 2.5 0. 5 11.5_ 0 Dec-11 0 0 10.5 0 Jul-12 0 0 14 0 4 F 1951 Aug-10 0 0 5 0 Jul-12 0 0 5 0 F 1941 Jul-10 0 0 4.5 11.5 Jan-11 5 1 4 12 Aug-11 20 0.8 7 12 Aug-12 20 0.8 6.5 11.5 6 M 1950 Feb-11 0 0 7 7 Aug-11 20 5 6.5 7 Jul-12 20 5 4 7 7 F 1958 May-11 0 0 5 0 Nov-11 0 0 8 0 May-12 _ 0 0 8.5 0 9 M 1928 Jan-11 10 0.5 11.5 0_5 Jul-11 10 0.5 7.5 0.5 Jan-12 30 1.3 85 0.5 Aug-12 25 1.05 7.5 0.5 F 1949 Jan-10 0 0 5.5 1.5 Jul-10 0 0 8.5 3.5 Jan-11 5 1 8.5 5.5 11 F 1945 Oct-10 0 0 7.5 0 Apr-11 0 0 7.5 0 Oct-11 0 0 7.5 0 Apr-12 20 5 8 0 Oct-12 20 5 0.5 0 12 F 1945 May-11 10 2 5.5 Dec-11 10 2 11 13.5 Jul-12 22.5 5.5 0 11.5 22313576.1 12 CA 02800186 2012-12-28 , Blakes Ref. 78863/00001 Case # Gender Date of Date of Ocular lutein (mg) Zeaxanthin (mg) OD lesion OS lesion Birth Examination (units) (units) 13 M 1931 Apr-10 0 o 8.5 0.5 May-11 0 o 9.5 o Nov-11 0 0 9 0 May-12 18 0 0 0 _ 14 May-10 0 0 0.5 0 May-12 0 0 , 12 o , ivi _ 1946 Nov-12 _ 0 _ 0 12 0 15 F 1934 Mar-09 0 0 8.5 9 Apr-10 _ 10 0.5 10 , 11 May-11 7.5 0.37 9.5 8.5 May-12 5 1 9.5 9 Dec-12 60 15 9.5 9.5 16 F 1949 Apr-12 o 0 0 , 13.5 Oct-12 20 5 11.5 , 14.5 Nov-12 20 _ 5 10 , 9.5 17 M 1941 Mar-10 0 0 7.5 , 0.5 Sep-10 , o 0 6.5 0.5 Apr-11 0 0 0 _ 0.5 Sep-11 o 0 0.5 0 18 M 1943 Feb-09 0 0 6.5 , 9.5 Jul-10 0 0 0.5 10.5 _ Jan-11 10 2 0.5 9.5 Jul-11 10 2 0 8.5 Jan-12 10 2 0.5 _ 8 Jun-12 20 5 0.5 _ 8 Dec-12 20 _ 5 . 0.5 , 4 19 M 1941 _ Sep-08 0 0 0 _ 0.5 _ Sep-09 o _ 0 0.5 0 _ Jan-10 0 o 0.5 0.5 _ Sep-10 0 0 0 _ 7.5 _ Oct-11 10 2 0 8.5 _ Apr-12 20 5 0 _ 0.5 _ Oct-12 20 5 o_ o 20 F 1944 .
Jun-09 10 0.5 05 0 _ _ Dec-09 10 0.5 0 _ _ 0.
Jun-10 5 0.25 105 _ _ _ 0 Dec-10 5 0.25 8 _ _ _ Jul-12 5 0.25 2.0 o Dec-12 5 0.25 1.5 0 _ 21 F 1948 _ Jun-09 0 0 0 0 _ Jun-11 0 0 0 11 _ Feb-12 20 0.8 0.5 8.5 _ Sep-12 20 0.8 0.5 7.5 22 F 1926 _ Jan-09 0 0 0 0 _ Sep-09 2.5 0.125 4 0 Feb-10 -- -- 4 0 22313576.1 13 Blakes Ref. 78863/00001 Case # Gender Date of Date of Ocular Lutein (mg) Zeaxanthin (mg) OD lesion OS lesion Birth Examination (units) (units) Apr-11 2.5 0.5 4 0 23 F 1946 Mar-10 0 0 0.5 0 Oct-10 0 0 8 0 Apr-11 0 0 7 0 Nov-11 20 5 6.5 0 Apr-12 20 5 0.5 0 24 F 1954 Jun-11 0 0 11.5 0 Dec-11 20 5 8.5 0 Jul-12 20 5 7 0 25 M 1949 Jul-09 0 0 0 0 Mar-12 0 0 12 0 Apr-10 0 0 4.5 0 Apr-11 0 0 4 0 Oct-11 10 2.5 0 0 26 M 1929 Apr-12 10 2.5 0 0 27 F 1951 Dec-08 0 0 0.5 0.5 Jan-10 0 1 0.5 0.5 Jul-10 5 1 0.5 0.5 Mar-11 5 1 2 2 Dec-11 5 0.8 7.5 6.5 Jul-12 20 0.8 4.5 8 28 M 1941 Jun-10 0 0 1 0.5 Nov-11 0 0 10.5 8.5 May-12 20 0.8 , 9.5 8.5 Dec-12 20 5 5 4.5 29 M 1930 Oct-07 0 0 0 0 Jul-09 0 0 0 0 Moderate pucker; VA
Jun-11 o 0 20/25 0 Mild pucker; VA
Dec-11 0 0 20/25 0 Mild pucker; VA
Jun-12 20 5 20/25 0 Mild pucker; VA
Dec-12 20 5 20/25 0 30 M 1948 Jul-09 0 0 9 N/A
Oct-09 5 0.25 10 N/A
Oct-09 5 0.25 10.5 N/A
Dec-09 10 0.5 10.5 N/A
11.5; plh Apr-12 5 0.25 0.4 cm N/A
10.5; plh Aug-12 20 5 0.2 cm N/A
22313576.1 14 Blakes Ref. 78863/00001 Case # Gender Date of Date of Ocular Lutein (mg) Zeaxanthin (mg) OD lesion OS lesion Birth Examination (units) (units) _ 31 M 1951 Aug-09 0 0 0 5.5 Sep-10 0 0 o 5.5 _ Aug-12 5 0 o 0.5 32 M 1951 Feb-10 0 0 o 0 Sep-11 0 o 11 0 Sep-12 20 5 5.5 0 33 F 1946 _ Sep-10 0 o 0 0.5 Sep-11 0 o 0 0.5 0.5;
Mar-12 20 5 0 Cataract 0.5;
Sep-12 5.7 1.4 0 Cataract 34 F 1937 Jan-09 0 o 0.5 12 Jan-10 0 0 0 13 Nov-10 0 0 o 15.5 Jun-11 0 0 0 15 Feb-12 10 2 o 6.4 Aug-12 10 2 0 3.8 35 M 1930 Jun-07 0 o 0.5 0 Nov-10 0 0 12 0 Jun-11 10 o 9.5 0 .. Aug-12 10 o 4.5 0 36 F 1952 Oct-10 0 0 11.5 9 Aug-12 5 1 11 6 37 M 1946 Jun-09 0 0 0 0 Jun-10 0 0 0 0.5 Jun-11 0 0 0.5 1 Jul-12 0 0 o 9 38 F 1946 Jan-10 0 0 0 4.3 Jan-12 0 0 0 8 Jul-12 20 5 0 0 39 M 1942 Nov-09 0 o 0 0 May-10 10 , 0.5 0 0 Aug-10 10 0.5 10.5 2.5 Nov-10 10 0.5 10.5 2.5 Apr-12 10 0.5 9.5 2.5 40 F 1957 Jan-10 0 0 6.4 0 Jul-10 10 2 5.1 0 Jan-11 10 2 4.6 0 Jul-11 10 2 4.3 0 Feb-12 10 2 , 3.2 0 Mar-12 10 2 2.7 0 Sep-12 0 _ 0 - --Oct 11, 2012 10 2 -- --Oct 18, 2012 0 0 4 6 41 M 1970 Nov 1, 2012 20 5 -- --22313576.1 15 Blakes Ref. 78863/00001 Case # Gender Date of Date of Ocular Lutein (mg) Zeaxanthin (mg) OD lesion OS lesion Birth Examination (units) (units) Nov 30, 2012 20 5 4 2 [0079] Results: Treatment of retinal lesions with some combination of lutein and zeaxanthin 3 was useful for ameliorating and decreasing the size of retinal lesions in subjects having VMT.
4 Subjects with a total of 42 retinal lesions were treated with some combination of lutein and zeaxanthin. 59.5% of retinal lesions decreased in size following treatment, 28.5% of retinal 6 lesions increased in size following treatment and 12% of lesions showed no change in size 7 following treatment with some combination of lutein and zeaxanthin (Table 1).
8 [0080] Daily oral administration to a subject of 10-20 mg lutein and 0.5-5 mg zeaxanthin 9 was sufficient to decrease retinal lesions in the majority of subjects who had not previously been treated with Lutein and/or zeaxanthin (Table 2).
11 [0081] Table 2: Change in retinal lesion size in patients treated with a combination of 10-12 20mg lutein and 0.5-5mg zeaxanthin. N/A is provided where no lesion was present. Negative 13 values indicate lesions that decreased in size following treatment.
Positive values indicate 14 lesions that increased in size following treatment.
Case Number Change in OD Lesion Size (units) Change in OS Lesion Size (units) 6 -3.0 0.0 11 -7.0 N/A
16 +10.0 -4.0 18 0.0 -6.5 19 N/A -7.5 21 +0.5 -3.5 23 -6.5 N/A
24 -4.5 N/A
26 -4.0 N/A
28 -5.5 -4.0 32 -5.5 N/A
22313576.1 16 Slakes Ref. 78863/00001 34 N/A -11.2 38 N/A -8.0 39 +9.5 +2.5 40 -3.7 N/A
2 [0082] Twenty-one lesions were treated in 15 patients. Twelve OD
lesions treated, eight 3 decreased with treatment, three increased, one showed no change. Nine OS
lesions were 4 treated, seven decreased in response to treatment, one increased and one neither increased nor decreased. In total, 21 lesions were treated, 71% decreased in response to treatment, 19%
6 increased in response to treatment and 10% showed no change.
7 [0083] Daily administration to subjects of 20 mg lutein and 5 mg zeaxanthin was sufficient to 8 decrease lesions in the majority of subjects who had not previously been treated with Lutein 9 and/or zeaxanthin (Table 3).
[0084] Table 3: Change in retinal lesion size in patients treated with a combination of 20mg 11 lutein and 5mg zeaxanthin. NIA is provided where no lesion was present.
Negative values 12 indicate lesions that decreased in size following treatment. Positive values indicate lesions that 13 increased in size following treatment.
Case Number Change in OD Lesion Size (units) Change in OS Lesion Size (units) 6 -3.0 0.0 11 -7.0 N/A
16 +10.0 -4.0 23 -6.5 N/A
24 -4.5 N/A
32 -5.5 N/A
38 N/A -8.0 14 [0085] Nine lesions treated in seven patients. Seven lesions decreased in response to treatment (78%), one increased in response to treatment (11%) and one lesion remained the 16 same size (11%).
22313576.1 17 Blakes Ref. 78863/00001 1 [0086] Discussion: Observational data suggests that increasing the daily dosage of lutein to 2 about 20mg and increasing the daily dosage of zeaxanthin to about 5mg results in efficient 3 decrease of retinal lesion size in subjects with VMT (Table 1, in particular cases 1, 2, 6, 11, 12, 4 19, 23, 24, 28, 32 and 38).
[0087] Although the invention has been described with reference to certain specific 6 embodiments, various modifications thereof will be apparent to those skilled in the art without 7 departing from the purpose and scope of the invention as outlined in the claims appended 8 hereto. Any examples provided herein are included solely for the purpose of illustrating the 9 invention and are not intended to limit the invention in any way. Any drawings provided herein are solely for the purpose of illustrating various aspects of the invention and are not intended to 11 be drawn to scale or to limit the invention in any way. The disclosures of all prior art recited 12 herein are incorporated herein by reference in their entirety.
=
22313576.1 18
8 [0003] Vitreomacular traction (VMT) is an idiopathic disorder, wherein the vitreous gel 9 strongly adheres to the retina. With ageing, it is common for the vitreous to separate from the retina. However, if separation is incomplete, the retina is pulled by the vitreous. This "traction"
11 force generated by vitreal pulling on the retina can cause edema within the retina, vessel 12 damage, bleeding, optic nerve damage, retinal distortion and decreased visual acuity (VA).
13 Adhesion size and strength of the traction force determine the resulting ocular pathology and 14 symptoms. Continuous VMT may induce retinal lesions, leading to VMT
syndrome.
Complications related to VMT syndrome include, but are not limited to, epiretinal membrane 16 (ERM), macular pucker, partial lamellar holes, macular holes, visual impairment and blindness.
17 [0004] Some VMT disorders are asymptomatic. Treatment for asymptomatic VMT involves 18 regular monitoring of the patient for further progression of VMT. In cases where VMT causes 19 reduced or distorted vision in a patient, the current standard of care is pars plana vitrectomy.
Vitrectomy requires surgical removal of the vitreous from the eye and membrane peeling to 21 relieve epiretinal traction. Complications of vitrectomy can include retinal tearing or detachment, 22 endopthalmitis and postoperative cataracts and fibrovascular membranes.
23 [0005] On October 17, 2012 the United States Food and Drug Administration (FDA) 24 approved a biological agent for treatment of VMT called Jetrea TM
(ocriplasmin;
ThromboGenics). Ocriplasmin, a proteolytic enzyme that cleaves fibronectin, laminin and 26 collagen, is to be provided to a patient by intravitreal injection to resolve vitreomacular adhesion, 27 which can result in VMT. Ocriplasmin does not reverse fibrosis.
28 [0006] Less invasive methods of treating symptomatic VMT are desirable.
22313576.1 1 Blakes Ref. 78863/00001 1 [0007] Nutrition is one feature of ocular health that has been studied in age-related ocular 2 diseases such as age-related macular degeneration (AMD). Macular degeneration is a chronic 3 eye disease that causes vision loss in the central field of vision. Dry macular degeneration is 4 marked by deterioration of the deep layers of the retina. Wet macular degeneration is characterized by blood vessels that grow under the retina, leaking blood and fluid. The 6 pathology of AMD is believed to be caused, at least in part, by oxidative damage (Beatty et al., 7 Surv. Opthamol. 2000,45:115-134; Cal et al., Prog. Retin. Eye Res. 2000, 29:263-271, 8 incorporated herein by reference as if set forth in their entirety). The healthy eye contains 9 antioxidant molecules, including enzymes, vitamins C and E, omega-3 fatty acid docosahexanic acid (DHA) and macular pigments lutein and zeaxanthin. Deficiency of antioxidants in the 'II ageing eye is believed to be a risk factor for development of AMD
(Ocular Nutrition: It's Role in 12 Maintaining Eye Health, Module 1: Nutrition and Health of the Aging Eye,2011, 6 pages, 13 incorporated herein by reference as if set forth in its entirety). It follows that nutrient 14 supplements, including antioxidants such as, zinc, vitamin C, vitamin E, beta carotene, lutein, zeaxanthin and omega-3 fatty acids, are sometimes recommended to prevent AMD
progression 16 and improve vision.
17 [0008] Lutein and zeaxanthin are xanthophyll carotenoid pigments found in the macula.
18 Subjects having AMD are known to have decreased amounts of lutein and zeaxanthin in their 19 macula. Some studies suggest that visual acuity, contrast sensitivity, and the amount of macular pigment in the human eye can be improved as a result of lutein and zeaxanthin supplementation 21 or a combination of these xanthophylls with other antioxidants (Stiles et al. (2004) Optometry, 22 75:216-230, incorporated herein by reference as if set forth in its entirety). Other studies 23 suggest that macular pigment optical density (MPOD), a measure of the amounts of lutein and 24 zeaxanthin in the macula of the living human eye, is a marker of the health of the human eye (U.S. Patent Application Publication No. 2012/0070422, incorporated herein by reference as if 26 set forth in its entirety).
27 [0009] Nutritional supplements including lutein and zeaxanthin have also been suggested to 28 promote ocular health and treat "ocular diseases" (see, for example, U.S. Patent Application 29 Publication Nos. 2010/0068298 and 2012/0258168, each incorporated herein by reference as if set forth in their entirety). However, the range of "ocular diseases" appears to be limited to AMD
31 and related ocular disorders thought to be associated with oxidative stress (U.S. Patent 32 Application Publication No. 2010/0068298). Similarly, "ocular health" is thought to decrease 33 naturally with age, and can be compromised by oxidative stress, illness and visual stresses, 22313576.1 2 Blakes Ref. 78863/00001 1 such as prolonged exposure to visual display monitors (U.S. Patent Application Publication No 2 2012/0258168). Vitreomacular traction has not been considered in such studies of treating 3 "ocular disease" or "ocular health".
4 [0010] Nutritional treatment of VMT has not been suggested in the literature or established in the field, but is desirable as a non-invasive alternative to treatment with vitrectomy or 6 intravitreal injections.
8 [0011] In one aspect, the present invention provides use of a composition comprising lutein 9 and zeaxanthin for treatment of a retinal disorder. In an embodiment of the aspect, the use comprises administering to a subject in need thereof a therapeutically effective amount of the 11 composition comprising lutein and zeaxanthin.
12 [0012] In some embodiments of the aspect the retinal disorder is vitreomacular traction 13 disorder. In some embodiments of the aspect the retinal disorder is a nutritional deficiency 14 disorder.
[0013] In some embodiments of the aspect the therapeutically effective amount of lutein is 16 about 10-20mg daily. In some embodiments of the aspect the therapeutically effective amount 17 of zeaxanthin is about 0.5-5 mg daily. In some embodiments of the aspect 20mg lutein and 18 5mg zeaxanthin are administered to the subject daily.
19 [0014] In some embodiments, the composition is administered orally to the subject. In some embodiments, the composition is administered daily for two to 24 months.
21 [0015] In some embodiments, the composition further comprises at least one of omega 3 22 fatty acids and probiotics. In some embodiments fatty acids are at least one of 23 Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA). In some embodiments the 24 probiotics are live microorganisms belonging to the order Lactobacilliales or the genus Bifidobacterium.
27 [0016] The features of the invention will become more apparent in the following detailed 28 description in which reference is made to the appended drawings wherein:
22313576.1 3 Blakes Ref. 78863/00001 1 [0017] FIGS. 1A-H depict ocular photos obtained from the subject of case 1. A: OD, 2 October, 2009; B: OS, October, 2009; C: OD, November, 2010; D: OS, November, 2010; E: OD, 3 November, 2011; F: OS, November, 2011; G: OD, May, 2012; and H: OS, May, 2012.
4 [0018] FIG. 2 depicts changes in retinal lesion size in the subject of case 1. Changes in retinal lesion size are indicated on the Y axis, treatment and time are indicated on the x axis.
6 L(20)Z(0) on the Y axis refers to administration of 20 mg lutein every other day. All other 7 treatments were administered on a daily basis.
8 [0019] FIGS. 3A-D depict ocular photos obtained from the subject of case. A: OD, October 9 12, 2012; B: OS, October 12, 2012; C: OD, November 15, 2012; D: OS, November 15, 2012.
[0020] FIGS. 4A-F depict ocular photos obtained from the subject of case 19. A: OD, 11 September 2009; B: OS, September 2009; C: OD, September 2010; D: OS, September 2010;
12 E: OD, April 2012; F: OS, April 2012.
13 [0021] FIGS. 5 A-D depict ocular photos obtained from the subject of case 38. A: OD, 14 January 2012; B: OS, January 2012; C: OD, July 2012; D: OS, July 2012.
[0022] FIGS. 6 A-D depict ocular photos obtained from the subject of case 41. A: OD, 16 October, 2012; B: OS, October, 2012; C: OD, November, 2012; and D: OS, November, 2012.
18 [0023] The present invention is based upon the inventor's observation that vitreomacular 19 traction (VMT) can be treated in subjects, in need thereof, by daily administration of a composition comprising lutein and zeaxanthin. A portion of the inventor's observations were 21 presented by the inventor at a meeting of The American Academy of Optometry, Ocular 22 Nutrition Special Interest Group, on Wednesday, October 24, 2012, and by another who is not 23 an inventor of the present invention at the same meeting on the same date.
24 [0024] The definitions of certain terms as used in this specification are provided below.
Unless defined otherwise, all technical and scientific terms used herein generally have the same 26 meaning as commonly understood by one of ordinary skill in the art to which this invention 27 belongs.
28 [0025] As used herein, the term "about" will be understood by persons of ordinary skill in the 29 art and will vary to some extent depending upon the context in which it is used. If there are uses 2313576.1 4 Blakes Ref. 78863/00001 1 of the term which are not clear to persons of ordinary skill in the art, given the context in which it 2 is used, "about" will mean up to plus or minus 10% of the enumerated value.
3 [0026] As used herein, the "administration" of an agent to a subject includes any route of 4 introducing or delivering to a subject a compound to perform its intended function.
Administration can be carried out by any suitable route, including orally, intraocularly, 6 intranasally, or topically. Administration includes self-administration and the administration by 7 another.
8 [0027] As used herein the term "probiotic" refers to live microorganisms that may confer a 9 health benefit on their host. Probiotics can be consumed as part of fermented foods or as dietary supplements. Examples of probiotic organisms include some members of the Order 11 Lactobacillales, such as Lactobacillus spp. And members of the genus Bifidobacterium.
12 [0028] As used herein, the term "nutraceutical" refers to specific chemical compounds found 13 in foods that can prevent disease or ameliorate an undesirable condition.
14 [0029] As used herein, the term "retinal disorder" or "disorder of the retina" refers to any impairment of normal physiological function of the retina.
16 [0030] As used herein, the term "nutritional deficiency disorder"
refers to an impairment of 17 normal physiological function of the retina, wherein the cause of impairment is the lack of one or 18 more nutrients.
19 [0031] As used herein, the term "Oculus Dexter' or "OD" refers to the right eye of a subject.
[0032] As used herein, the term "Oculus Sinister" or "OD" refers to the left eye of a subject.
21 [0033] As used herein, the term "omega 3 fatty acids" refers to fats commonly found in 22 marine and plant oils, such as fish oils, algal oil, squid oil, echium oil and flaxseed oil. Examples 23 of omega 3 fatty acids useful in the present invention include, but are not limited to, 24 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA).
[0034] As used herein, the term "therapeutically effective amount" refers to a quantity 26 sufficient to achieve a desired therapeutic and/or prophylactic effect, e.g., an amount which 27 results in the prevention of, or a decrease in, the symptoms associated with a retinal disorder.
28 For example, a "therapeutically effective amount" of the composition of the present invention 29 refers to levels of the composition that, when administered to the subject on a daily basis, 22313576.1 5 Blakes Ref. 78863/00001 1 ameliorate, in part or in full, at least one symptom of the disorder, for example, the size of a 2 retinal lesion.
3 [0035] As used herein, the term "lesion" refers to a localized change in an organ or tissue of 4 the body. "Retinal lesions", referred to herein, can be characterized by at least one of puckering, fibrosis, lamellar splitting, and/or dragging, swelling, bulging of retinal tissues and 6 retinal holes.
7 [0036] As used herein, the terms "treating" or "treatment" or "alleviation" refers to both 8 therapeutic treatment and prophylactic or preventative measures, wherein the object is to 9 reverse, prevent or slow down (lessen) the targeted pathologic condition or disorder. A subject is successfully "treated" for a retinal disorder if, after receiving an effective therapeutic amount 11 of the composition according to the methods described herein, the subject shows measurable 12 reduction in at least one symptom or sign of a retinal disorder. It is also to be appreciated that 13 the various modes of treatment or prevention of medical conditions as described are intended to 14 mean "substantial", which includes total but also less than total treatment or prevention, and wherein some biologically or medically relevant result is achieved.
16 [0037] As used herein, the terms "vitreomacular traction,"
"vitreomacular traction disorder"
17 and "vitreoretinal traction" refer to a conditions wherein the vitreous gel of the human eye 18 adheres to the retina, causing pulling, or "traction", forces on the retina that can cause ocular 19 damage.
[0038] As used herein, the terms "units of diameter" and units made in reference to lesion 21 size or diameter refer to units of diameter of the posterior pole of an eye, which measures ten 22 units in diameter between the vascular arcades. A lesion can be larger than 19 units.
23 [0039] The terms "comprise", "comprises", "comprised" or "comprising"
may be used in the 24 present description. As used herein (including the specification and/or the claims), these terms are to be interpreted as specifying the presence of the stated features, integers, steps or 26 components, but not as precluding the presence of one or more other feature, integer, step, 27 component or a group thereof as would be apparent to persons having ordinary skill in the 28 relevant art.
29 [0040] Non-invasive methods for treating vitreomacular traction (VMT) and related disorders have been highly desired. The present invention provides methods for treating VMT using a 22313576.1 6 Blakes Ref. 78863/00001 1 nutraceutical composition. A person of skill in the art understands that nutraceutical compounds 2 are found in foods and can be used to prevent disease or ameliorate an undesirable condition.
3 [0041] In some embodiments of the present invention, the methods involve identifying a 4 subject in need of VMT treatment and administering to the subject a therapeutically effective daily dose of a composition comprising lutein and zeaxanthin.
6 [0042] Subjects in need of VMT treatment typically have a retinal lesion in one or both eyes.
7 Retinal lesions can be detected using methods known to those of skill in the art, at least for 8 example, retinal photography, optical coherence tomography, OCT, visual acuity, Amsler grid or 9 fundus examination [0043] In one embodiment of the present invention, therapeutically effective dosages of 11 lutein and zeaxanthin for treatment of VMT include about 10-20mg lutein and about 0.5-5mg 12 zeaxanthin. Preferably, a ratio of 4:1 lutein: zeaxanthin is provided to a subject for treatment of 13 VMT. An especially preferred therapeutically effective daily dose of a composition comprising 14 lutein and zeaxanthin comprises 20mg lutein and 5mg zeaxanthin.
[0044] In some embodiments of the present invention, the composition is administered to 16 the subject orally. The compositions of the invention can be formulated with suitable carriers 17 such as starch, sucrose or lactose in tablets, capsules, solutions, powders, syrups and 18 emulsions, or oils. Suitable optional carriers include but are not limited to, for example, fatty 19 acids, esters and salts thereof, that can be derived from any source, such as for example, natural or synthetic oils, fats, waxes or combinations thereof. In preferred embodiments of the 21 present invention, the source of the fatty acids is DHA or EPA, which may be provided in 22 combination with the composition or separately.
23 [0045] In some embodiments of the present invention, the composition is administered daily 24 for two to 24 months to the subject. In preferred embodiments, the composition is administered daily to the subject for 3 months. In particularly preferred embodiments of the present invention, 26 the composition is administered to the subject daily until retinal lesions are ameliorated 27 completely.
28 [0046] In one embodiment of the present invention, the method is used for treating VMT. In 29 other embodiments of the present invention, the method is used for treating retinal disorders related to VMT, such as, for example, epiretinal membrane (ERM), macular pucker, partial 31 lamellar holes and/or macular holes.
22313576.1 7 Blakes Ref. 78863/00001 1 [0047] It is contemplated herein, that idiopathic VMT and related retinal disorders are 2 associated with an underlying nutritional deficiency disorder, wherein the subject having the 3 disorder is deficient in at least lutein and zeaxanthin. It is further contemplated that such 4 nutritional deficiency can be corrected in a subject in need of VMT
treatment by administering to the subject therapeutically effective amounts of lutein and zeaxanthin, daily.
6 [0048] It is contemplated herein that treatment of VMT with lutein and zeaxanthin can be 7 further improved by administering to the subject one or more omega 3 fatty acid and/or 8 probiotic.
9 [0049] EXAMPLES
[0050] The present invention is further illustrated by the following examples, which should 11 not be construed as limiting in any way.
12 [0051] Example 1: Materials and Methods 13 [0052] Diagnosis of vitreomacular traction (VMT): VMT can be symptomatic or 14 asymptomatic. Complaints of reduced or distorted vision may or may not be reported by the subject. Measurement of visual acuity (VA) may or may not be normal or reduced in one or both 16 eyes. Measurement for distortion on an Amsler grid may or may not show distortion in one or 17 both eyes. Retinal photography may show signs of VMT in the original color composite image 18 (e.g., upper left photo in four panel photo of FIG. 1A). Further analysis of the choroid (e.g., 19 upper right photo in four panel photo of FIG. 1A), the retina (e.g., lower left photo in four panel photo of FIG. 1A), and the retinal nerve fibre layer (RNFL) (e.g., lower right photo in four panel 21 photo of FIG. 1A), may reveal puckering, fibrosis, lamellar splitting, partial lamellar holes, 22 pseudo macular holes, bulging and/or edema in the choroid, retinal and/or RNFL images.
23 Further analysis with "3-D" images of the choroid, retina and RNFL
layers may show elevations 24 diagnostic of VMT, such as, for example, the presence, severity and/or size of puckering, partial lamellar holes, macular holes, bulging or edema. Further, "3-D" images can be useful for 26 determining which layers of the eye tissue are affected by VMT.
27 [0053] Ocular imaging: retinal photographs were taken using a Canon CR-1 Digital Retinal 28 Camera and analyzed using EyeScape Digital Imaging Software, version 7.5.5.
29 [0054] The settings used for taking retinal photographs were such that optimal contrast and brightness for each subject was achieved. Most retinal photographs were taken with a dilated 22313576.1 8 Blakes Ref. 78863/00001 1 pupil. Some subjects have naturally very large pupils. In these cases, pupil dilation may not 2 have been required to obtain sufficient images. The Canon CR-1 has a setting for small pupils 3 that was used as required.
4 [0055] Example 2: Case 1.
[0056] Subject Description: The subject is a male born in 1938. Subject underwent laser 6 therapy for retinal detachment in his left eye in 2002. An ophthalmological examination in 7 December 2008 revealed ERM in the subject's OS.
8 [0057] Treatment: Subject began administration of 20 mg lutein every second day in June 9 2009 and continued for 4 months. From October 2009 through October 2010 the subject was administered 3 times daily, 1000 mg omega-3 fatty acids from fish oil. From November 2010 11 through November 2011 the subject was administered daily with 10 mg lutein and 2.0 mg 12 zeaxanthin. From December 2011 through October 2012, the subject was administered daily 13 with 20 mg lutein and 5 mg zeaxanthin.
14 [0058] Results: Four months of treatment with lutein (10 mg) every other day resulted in reduction of ERM OD from 1.5 units to 0.5 units and a reduction of OS macular pucker from 6.5 16 units to 5.0 units (FIG. 1, A, B). During the following 12 months, in the absence of supplemental 17 lutein and zeaxanthin, lesions in the subject's right and left eyes increased (FIG. 2). The 18 subject's ERM OD increased from 0.5 units to 4.5 units and OS macular pucker increased from 19 5 units to 8 units (FIGS. 1C and 1D relative to 1A and 16, respectively). From November 2010 through November 2011, treatment with 10 mg lutein and 2.0 mg zeaxanthin, resulted in a 21 decrease in retinal lesion size in both of the subject's eyes (FIG. 2).
The subject's ERM OD
22 decreased from 4.5 units to 2 units and OS macular pucker decreased from 8 units to 4 units 23 (FIGS. lE and 1F relative to FIGS. 1C and 1D, respectively). Further treatment with an 24 increased dose of lutein (20 mg/day) and zeaxanthin (5 mg/day) for 11 months resulted in further decrease in retinal lesion size (FIGS. 1G and 1H relative to FIGS. 1E
and 1F, 26 respectively). Treatment with 20 mg/day lutein and 5 mg/day zeaxanthin was sufficient to 27 completely ameliorate the lesion in the subject's left eye.
28 [0059] Example 3: Case 16.
29 [0060] Subject Description: The subject is a female born in 1949.
Subject had normal retinal health in December, 2010. April 2012, the subject had ERM OS of 13.5. October 12, 2012, 31 subject had lesions in both eyes, OD 11.5 units, OS 14.5 units.
2231.3576.1 9 Blakes Ref. 78863/00001 1 [0061] Treatment: The subject was administered 20 mg/day lutein and 5 mg/day 2 zeaxanthin on an irregular basis from April 2012 until October 11, 2012.
The subject was 3 administered daily 20 mg lutein and 5 mg zeaxanthin from October 12, 2012 through November 4 15,2012.
[0062] Results: Following about one month of regular administration of lutein and 6 zeaxanthin, the subject's lesion size and severity decreased in both eyes: OD lesion decreased 7 from 11.5 to 10 units, the OS lesion decreased from 14.5 to 9.5 units.
8 [0063] Example 4: Case 19.
9 [0064] Subject Description: The subject is a male born in 1941.
Subject had OD lesion of 0.5 units in September 2009. January 2010, the subject had OD and OS lesions of 0.5 units.
11 Further, the subject has been diagnosed with diabetes in January 2010 and was being treated 12 with metformin. September 2010, subject had no OD lesion and an OS
lesion of 7.5 units.
13 October 2011, subject's OS lesion had increased to 8.5 units. By December 2011, the subject 14 was no longer diabetic and was no longer taking metformin. April 2012, subjects' OS lesion had decreased to 0.5 units. October 2012, subject's OS lesion had been ameliorated 16 [0065] Treatment: The subject was administered 10 mg lutein and 2.0 mg zeaxanthin daily 17 from October 2010 until October 2011. The subject was administered 20 mg lutein and 5 mg 18 zeaxanthin daily from November 2011 through October, 2012.
19 [0066] Results: Twelve months of treatment with lutein (10 mg) and zeaxanthin (2.0 mg) resulted in an increase in OS lesion size from 7.5 units to 8.5 units (FIG. 3, C, D). Further 21 treatment with an increased dose of lutein (20 mg/day) and zeaxanthin (5 mg/day) for 6 months 22 was sufficient to completely ameliorate the OS lesion (FIG. 3F).
23 [0067] Example 5: Case 38.
24 [0068] Subject Description: The subject is a female born in 1946. The subject is diabetic.
Subject had ERM OS lesion of 4.3 units in January 2010. OS lesion had increased to 8 units by 26 January 2012. July 2012, subject's ERM OS lesion had been ameliorated.
27 [0069] Treatment: The subject was administered 20 mg lutein and 5 mg zeaxanthin daily 28 from January 2012 through July 2012.
22313576.1 10 Blakes Ref. 78863/00001 1 [0070] Results: Six months of treatment with lutein (20 mg/day) and zeaxanthin (5 mg/day) 2 was sufficient to completely ameliorate the ERM OS lesion in the subject (FIG. 5D).
3 [0071] Example 6: Case 41.
4 [0072] Subject Description: The subject is a male born in 1970.
Subject developed central serous retinopathy in both eyes, September 17, 2012. OS became symptomatic with VA 20/40 6 and large area of "bulging lines" on Amsler grid. Subject's OD lesion was 4 units and OS lesion 7 was 6 units on October 18, 2012. Subjects OD lesion was 4 units, but improving on November 8 30, 2012 and subject's OS lesion had been ameliorated by the same date;
OS VA 20/20, 9 Amsler grid greatly improved relative to October 18, 2012 measurement.
[0073] Treatment: The subject was administered 10 mg lutein and 2.0 mg zeaxanthin daily 11 for one week commencing on October 11, 2012. At this time the subject was also administered 12 daily with 360mg EPA and 240 mg DHA. The subject was administered no lutein or zeaxanthin 13 from October 18 through October 24, 2012, at which time the subject was administered daily 14 probiotics containing 5 billion live microorganism cells. From October 25, 2012 through November 30, 2012 the subject was administered daily with 20 mg lutein, 5 mg zeaxanthin, 16 360mg EPA, 240 mg DHA and probiotics containing 5 billion live microorganism cells.
17 [0074] Results: Within 6 weeks following treatment with lutein (20mg/day) zeaxanthin (5 18 mg/day), probiotics and omega 3 fatty acids the subject's OS VA returned to 20/20 and the 19 subject's Amsler distortion was greatly diminished. Further, treatment was sufficient to ameliorate the subject's OS lesion (FIG. 6D relative to FIG. 6B).
21 [0075] Example 7: Lutein and zeaxanthin dosage response trials indicate positive results for 22 treatment of VMT, including retinal lesions.
23 [0076] Subject Description: Data were collected from 40 subjects having symptomatic VMT
24 over a period of 4.5 years.
[0077] Treatment: Subjects were treated daily with lutein and zeaxanthin as described in 26 table 1.
27 [0078] Table 1: Raw data collected from subjects during preliminary lutein zeaxanthin trial.
28 Plh indicates partial lamellar hole. Pucker (macular) is described based on a qualitative score of 22313576.1 11 Blakes Ref. 78863/00001 mild to severe, wherein a score of 1of 3 is a mild pucker, a score of 2 of 3 is a moderate pucker 2 and a score of 3 of 3 is a sever pucker.
Case # Gender Date of Date of Ocular Lutein (mg) Zeaxanthin (mg) OD lesion OS lesion Birth Examination , (units) , (units) 1 M 1939 Jul-08 0 0 1.5 6 Oct-09 10 0 0.5 5 Nov-10 0 0 4.5, 8 Nov-11 10 2 2 4 May-12 20 5 .5 0 , Oct-12 20 5 0.5 0 _ 2 F 1959 Apr-09 0 0 0 8.5 _ Nov-10 20 0 0 3 -Mar-12 20 5 0 _ 0 Sep-12 0 0 1 0.5 3 M 1959 Apr-09 0 0 9 0 May-10 0 0 9 0 Jun-11 2.5 0. 5 11.5_ 0 Dec-11 0 0 10.5 0 Jul-12 0 0 14 0 4 F 1951 Aug-10 0 0 5 0 Jul-12 0 0 5 0 F 1941 Jul-10 0 0 4.5 11.5 Jan-11 5 1 4 12 Aug-11 20 0.8 7 12 Aug-12 20 0.8 6.5 11.5 6 M 1950 Feb-11 0 0 7 7 Aug-11 20 5 6.5 7 Jul-12 20 5 4 7 7 F 1958 May-11 0 0 5 0 Nov-11 0 0 8 0 May-12 _ 0 0 8.5 0 9 M 1928 Jan-11 10 0.5 11.5 0_5 Jul-11 10 0.5 7.5 0.5 Jan-12 30 1.3 85 0.5 Aug-12 25 1.05 7.5 0.5 F 1949 Jan-10 0 0 5.5 1.5 Jul-10 0 0 8.5 3.5 Jan-11 5 1 8.5 5.5 11 F 1945 Oct-10 0 0 7.5 0 Apr-11 0 0 7.5 0 Oct-11 0 0 7.5 0 Apr-12 20 5 8 0 Oct-12 20 5 0.5 0 12 F 1945 May-11 10 2 5.5 Dec-11 10 2 11 13.5 Jul-12 22.5 5.5 0 11.5 22313576.1 12 CA 02800186 2012-12-28 , Blakes Ref. 78863/00001 Case # Gender Date of Date of Ocular lutein (mg) Zeaxanthin (mg) OD lesion OS lesion Birth Examination (units) (units) 13 M 1931 Apr-10 0 o 8.5 0.5 May-11 0 o 9.5 o Nov-11 0 0 9 0 May-12 18 0 0 0 _ 14 May-10 0 0 0.5 0 May-12 0 0 , 12 o , ivi _ 1946 Nov-12 _ 0 _ 0 12 0 15 F 1934 Mar-09 0 0 8.5 9 Apr-10 _ 10 0.5 10 , 11 May-11 7.5 0.37 9.5 8.5 May-12 5 1 9.5 9 Dec-12 60 15 9.5 9.5 16 F 1949 Apr-12 o 0 0 , 13.5 Oct-12 20 5 11.5 , 14.5 Nov-12 20 _ 5 10 , 9.5 17 M 1941 Mar-10 0 0 7.5 , 0.5 Sep-10 , o 0 6.5 0.5 Apr-11 0 0 0 _ 0.5 Sep-11 o 0 0.5 0 18 M 1943 Feb-09 0 0 6.5 , 9.5 Jul-10 0 0 0.5 10.5 _ Jan-11 10 2 0.5 9.5 Jul-11 10 2 0 8.5 Jan-12 10 2 0.5 _ 8 Jun-12 20 5 0.5 _ 8 Dec-12 20 _ 5 . 0.5 , 4 19 M 1941 _ Sep-08 0 0 0 _ 0.5 _ Sep-09 o _ 0 0.5 0 _ Jan-10 0 o 0.5 0.5 _ Sep-10 0 0 0 _ 7.5 _ Oct-11 10 2 0 8.5 _ Apr-12 20 5 0 _ 0.5 _ Oct-12 20 5 o_ o 20 F 1944 .
Jun-09 10 0.5 05 0 _ _ Dec-09 10 0.5 0 _ _ 0.
Jun-10 5 0.25 105 _ _ _ 0 Dec-10 5 0.25 8 _ _ _ Jul-12 5 0.25 2.0 o Dec-12 5 0.25 1.5 0 _ 21 F 1948 _ Jun-09 0 0 0 0 _ Jun-11 0 0 0 11 _ Feb-12 20 0.8 0.5 8.5 _ Sep-12 20 0.8 0.5 7.5 22 F 1926 _ Jan-09 0 0 0 0 _ Sep-09 2.5 0.125 4 0 Feb-10 -- -- 4 0 22313576.1 13 Blakes Ref. 78863/00001 Case # Gender Date of Date of Ocular Lutein (mg) Zeaxanthin (mg) OD lesion OS lesion Birth Examination (units) (units) Apr-11 2.5 0.5 4 0 23 F 1946 Mar-10 0 0 0.5 0 Oct-10 0 0 8 0 Apr-11 0 0 7 0 Nov-11 20 5 6.5 0 Apr-12 20 5 0.5 0 24 F 1954 Jun-11 0 0 11.5 0 Dec-11 20 5 8.5 0 Jul-12 20 5 7 0 25 M 1949 Jul-09 0 0 0 0 Mar-12 0 0 12 0 Apr-10 0 0 4.5 0 Apr-11 0 0 4 0 Oct-11 10 2.5 0 0 26 M 1929 Apr-12 10 2.5 0 0 27 F 1951 Dec-08 0 0 0.5 0.5 Jan-10 0 1 0.5 0.5 Jul-10 5 1 0.5 0.5 Mar-11 5 1 2 2 Dec-11 5 0.8 7.5 6.5 Jul-12 20 0.8 4.5 8 28 M 1941 Jun-10 0 0 1 0.5 Nov-11 0 0 10.5 8.5 May-12 20 0.8 , 9.5 8.5 Dec-12 20 5 5 4.5 29 M 1930 Oct-07 0 0 0 0 Jul-09 0 0 0 0 Moderate pucker; VA
Jun-11 o 0 20/25 0 Mild pucker; VA
Dec-11 0 0 20/25 0 Mild pucker; VA
Jun-12 20 5 20/25 0 Mild pucker; VA
Dec-12 20 5 20/25 0 30 M 1948 Jul-09 0 0 9 N/A
Oct-09 5 0.25 10 N/A
Oct-09 5 0.25 10.5 N/A
Dec-09 10 0.5 10.5 N/A
11.5; plh Apr-12 5 0.25 0.4 cm N/A
10.5; plh Aug-12 20 5 0.2 cm N/A
22313576.1 14 Blakes Ref. 78863/00001 Case # Gender Date of Date of Ocular Lutein (mg) Zeaxanthin (mg) OD lesion OS lesion Birth Examination (units) (units) _ 31 M 1951 Aug-09 0 0 0 5.5 Sep-10 0 0 o 5.5 _ Aug-12 5 0 o 0.5 32 M 1951 Feb-10 0 0 o 0 Sep-11 0 o 11 0 Sep-12 20 5 5.5 0 33 F 1946 _ Sep-10 0 o 0 0.5 Sep-11 0 o 0 0.5 0.5;
Mar-12 20 5 0 Cataract 0.5;
Sep-12 5.7 1.4 0 Cataract 34 F 1937 Jan-09 0 o 0.5 12 Jan-10 0 0 0 13 Nov-10 0 0 o 15.5 Jun-11 0 0 0 15 Feb-12 10 2 o 6.4 Aug-12 10 2 0 3.8 35 M 1930 Jun-07 0 o 0.5 0 Nov-10 0 0 12 0 Jun-11 10 o 9.5 0 .. Aug-12 10 o 4.5 0 36 F 1952 Oct-10 0 0 11.5 9 Aug-12 5 1 11 6 37 M 1946 Jun-09 0 0 0 0 Jun-10 0 0 0 0.5 Jun-11 0 0 0.5 1 Jul-12 0 0 o 9 38 F 1946 Jan-10 0 0 0 4.3 Jan-12 0 0 0 8 Jul-12 20 5 0 0 39 M 1942 Nov-09 0 o 0 0 May-10 10 , 0.5 0 0 Aug-10 10 0.5 10.5 2.5 Nov-10 10 0.5 10.5 2.5 Apr-12 10 0.5 9.5 2.5 40 F 1957 Jan-10 0 0 6.4 0 Jul-10 10 2 5.1 0 Jan-11 10 2 4.6 0 Jul-11 10 2 4.3 0 Feb-12 10 2 , 3.2 0 Mar-12 10 2 2.7 0 Sep-12 0 _ 0 - --Oct 11, 2012 10 2 -- --Oct 18, 2012 0 0 4 6 41 M 1970 Nov 1, 2012 20 5 -- --22313576.1 15 Blakes Ref. 78863/00001 Case # Gender Date of Date of Ocular Lutein (mg) Zeaxanthin (mg) OD lesion OS lesion Birth Examination (units) (units) Nov 30, 2012 20 5 4 2 [0079] Results: Treatment of retinal lesions with some combination of lutein and zeaxanthin 3 was useful for ameliorating and decreasing the size of retinal lesions in subjects having VMT.
4 Subjects with a total of 42 retinal lesions were treated with some combination of lutein and zeaxanthin. 59.5% of retinal lesions decreased in size following treatment, 28.5% of retinal 6 lesions increased in size following treatment and 12% of lesions showed no change in size 7 following treatment with some combination of lutein and zeaxanthin (Table 1).
8 [0080] Daily oral administration to a subject of 10-20 mg lutein and 0.5-5 mg zeaxanthin 9 was sufficient to decrease retinal lesions in the majority of subjects who had not previously been treated with Lutein and/or zeaxanthin (Table 2).
11 [0081] Table 2: Change in retinal lesion size in patients treated with a combination of 10-12 20mg lutein and 0.5-5mg zeaxanthin. N/A is provided where no lesion was present. Negative 13 values indicate lesions that decreased in size following treatment.
Positive values indicate 14 lesions that increased in size following treatment.
Case Number Change in OD Lesion Size (units) Change in OS Lesion Size (units) 6 -3.0 0.0 11 -7.0 N/A
16 +10.0 -4.0 18 0.0 -6.5 19 N/A -7.5 21 +0.5 -3.5 23 -6.5 N/A
24 -4.5 N/A
26 -4.0 N/A
28 -5.5 -4.0 32 -5.5 N/A
22313576.1 16 Slakes Ref. 78863/00001 34 N/A -11.2 38 N/A -8.0 39 +9.5 +2.5 40 -3.7 N/A
2 [0082] Twenty-one lesions were treated in 15 patients. Twelve OD
lesions treated, eight 3 decreased with treatment, three increased, one showed no change. Nine OS
lesions were 4 treated, seven decreased in response to treatment, one increased and one neither increased nor decreased. In total, 21 lesions were treated, 71% decreased in response to treatment, 19%
6 increased in response to treatment and 10% showed no change.
7 [0083] Daily administration to subjects of 20 mg lutein and 5 mg zeaxanthin was sufficient to 8 decrease lesions in the majority of subjects who had not previously been treated with Lutein 9 and/or zeaxanthin (Table 3).
[0084] Table 3: Change in retinal lesion size in patients treated with a combination of 20mg 11 lutein and 5mg zeaxanthin. NIA is provided where no lesion was present.
Negative values 12 indicate lesions that decreased in size following treatment. Positive values indicate lesions that 13 increased in size following treatment.
Case Number Change in OD Lesion Size (units) Change in OS Lesion Size (units) 6 -3.0 0.0 11 -7.0 N/A
16 +10.0 -4.0 23 -6.5 N/A
24 -4.5 N/A
32 -5.5 N/A
38 N/A -8.0 14 [0085] Nine lesions treated in seven patients. Seven lesions decreased in response to treatment (78%), one increased in response to treatment (11%) and one lesion remained the 16 same size (11%).
22313576.1 17 Blakes Ref. 78863/00001 1 [0086] Discussion: Observational data suggests that increasing the daily dosage of lutein to 2 about 20mg and increasing the daily dosage of zeaxanthin to about 5mg results in efficient 3 decrease of retinal lesion size in subjects with VMT (Table 1, in particular cases 1, 2, 6, 11, 12, 4 19, 23, 24, 28, 32 and 38).
[0087] Although the invention has been described with reference to certain specific 6 embodiments, various modifications thereof will be apparent to those skilled in the art without 7 departing from the purpose and scope of the invention as outlined in the claims appended 8 hereto. Any examples provided herein are included solely for the purpose of illustrating the 9 invention and are not intended to limit the invention in any way. Any drawings provided herein are solely for the purpose of illustrating various aspects of the invention and are not intended to 11 be drawn to scale or to limit the invention in any way. The disclosures of all prior art recited 12 herein are incorporated herein by reference in their entirety.
=
22313576.1 18
Claims (22)
1. Use of a composition comprising lutein and zeaxanthin in the treatment of a retinal disorder.
2. The use of claim 1, wherein the retinal disorder is vitreomacular traction disorder.
3. The use of claim 1, wherein the retinal disorder is a nutritional deficiency disorder.
4. The use of any one of claims 1-3, wherein the composition comprises about 10 to 20 mg of lutein.
5. The use of any one of claims 1-4, wherein the composition comprises about 0.5 to 5 mg zeaxanthin
6. The use of any one of claims 1-5, wherein the composition comprises 20 mg lutein and 5mg zeaxanthin.
7. The use of any one of claims 1-6, wherein the composition is in a form for oral administration.
8. The use of any one of claims 1-6, wherein the composition is in a form for daily administration for two to 24 months.
9. The use of any one of claims 1-8, wherein the composition further comprises at least one of omega 3 fatty acids and probiotics.
10. The use of claim 9, wherein the fatty acids are at least one of Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA).
11. The use of claim 9, wherein the probiotics are live microorganisms belonging to the order Lactobacilliales or the genus Bifidobacterium.
12. Use of a composition comprising lutein and zeaxanthin for preparation of a medicament for treatment of a retinal disorder.
13. The use of claim 12, wherein the retinal disorder is vitreomacular traction disorder.
14. The use of claim 12, wherein the retinal disorder is a nutritional deficiency disorder.
15 The use of claim 12, wherein the composition comprises about 10 to 20mg lutein.
16. The use of claim 12, wherein the composition comprises about 0.5 to 5 mg zeaxanthin.
17. The use of claim 12, wherein the composition comprises 20 mg lutein and 5 mg zeaxanthin.
18. The use of any one of claims 12-17, wherein the composition is in a form for oral administration.
19. The use of any one of claims 12-18, wherein the composition is in a form for daily administration for two to 24 months.
20 The use of any one of claims 12-19, wherein the composition further comprises at least one of omega 3 fatty acids and probiotics.
21. The use of claim 20, wherein the fatty acids are at least one of Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA).
22. The use of claim 20, wherein the probiotics are live microorganisms belonging to the order Lactobacilliales or the genus Bifidobacterium.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2800186A CA2800186A1 (en) | 2012-12-28 | 2012-12-28 | Nutritional formulations and method for treating diseases |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA2800186A CA2800186A1 (en) | 2012-12-28 | 2012-12-28 | Nutritional formulations and method for treating diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2800186A1 true CA2800186A1 (en) | 2014-06-28 |
Family
ID=51022670
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2800186A Abandoned CA2800186A1 (en) | 2012-12-28 | 2012-12-28 | Nutritional formulations and method for treating diseases |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2800186A1 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015042724A1 (en) * | 2013-09-30 | 2015-04-02 | Dunning Barbara L | Detection of nutrient deficiencies influencing ocular health |
| RU2619991C1 (en) * | 2016-02-18 | 2017-05-22 | Павел Владимирович Лыскин | Method for vitreomacular traction syndrome treatment |
-
2012
- 2012-12-28 CA CA2800186A patent/CA2800186A1/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015042724A1 (en) * | 2013-09-30 | 2015-04-02 | Dunning Barbara L | Detection of nutrient deficiencies influencing ocular health |
| RU2619991C1 (en) * | 2016-02-18 | 2017-05-22 | Павел Владимирович Лыскин | Method for vitreomacular traction syndrome treatment |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103735733B (en) | A kind of compound preparation containing lutein ester and preparation method thereof | |
| CN103566049B (en) | Regard the composition of macular degeneration disease in eyes regarding macular pigment optical density and prevention or treatment age related for improving | |
| CN101731597B (en) | Blueberry fish oil capsule | |
| US20160067204A1 (en) | Therapeutic or prophylactic agent for corneal epithelium disorders and/or conjunctival epithelium disorders | |
| CN105520137B (en) | It is a kind of that there is the health food alleviated visual fatigue and protect visual function | |
| Greven et al. | Unusual manifestations of X-linked retinoschisis. | |
| US20050171214A1 (en) | Medicament for improving the failure of accommodation | |
| US20160235296A1 (en) | Detection of nutrient deficiencies influencing ocular health | |
| CA2800186A1 (en) | Nutritional formulations and method for treating diseases | |
| CN108324705A (en) | Composition for relieving asthenopia containing theanine, γ-aminobutyric acid and anthocyanidin | |
| CN102150860B (en) | Composition for easing visual fatigue and assisting in improving memory | |
| CN106617076A (en) | Composition for assisting in reducing blood lipid, preparation method of composition, and health-care food including composition | |
| Challiol et al. | Retinal toxicity due to canthaxanthin. Case series | |
| US20140186302A1 (en) | Nutritional Formulations and Method for Treating Diseases | |
| RU2489146C1 (en) | Method of treating "dry" form of age-related macular degeneration | |
| US20190374587A1 (en) | Composition for suppressing or improving eye fatigue | |
| WO2015165507A1 (en) | Treatment of eye diseases using omega 3 fatty acids and aa/epa blood ratio | |
| EP4033921B1 (en) | Composition of a dietary supplement and/or a nutritional additive for food, a unitary dosage form of said composition, and their use for improvement of the quality of visual performance including contrast sensitivity in persons in need of such an improvement, including persons suffering from at least one eye disease, particularly vitreous floaters | |
| Davey | Advances in the management of dry AMD | |
| Hsu et al. | Effects of Supplementation with Lutein Plus Docosahexaenoic Acid Oral Complex on Eye Dryness, Visual Function, and Memory Function in Healthy Subjects: A Single‐Arm Clinical Trial | |
| George et al. | Effect of raw quail egg on intraocular pressure and blood pressure of hypertensive subjects | |
| Jeffrey | What You Must Know About Dry Eye: How to Prevent, Stop, or Reverse Dry Eye Disease | |
| Kumar | ROLE OF TARPANA WITH PHALTRIKADI GHRITA IN THE MANAGEMENT OF DWITIYA PATALGATA TIMIRA WSR TO PRESBYOPIA | |
| Saljoughian | Nutrition and eye health at a glance | |
| JP2006141410A (en) | Foods and drinks having effect of relieving eye controlling function errors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20171228 |