Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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1 NUTRITIONAL FORMULATIONS AND METHOD FOR TREATING DISEASES
2 CROSS REFERENCE TO PRIOR APPLICATIONS
3 [0001] Not applicable.
4 FIELD OF THE INVENTION
[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.
7 BACKGROUND OF THE INVENTION
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.
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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,
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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.
7 SUMMARY OF THE INVENTION
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.
26 BRIEF DESCRIPTION OF THE DRAWINGS
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:
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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.
17 DETAILED DESCRIPTION OF THE INVENTION
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
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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,
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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
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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.
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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
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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.
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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.
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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
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1
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
12
Dec-11 10 2 11
13.5
Jul-12 22.5 5.5 0 11.5
22313576.1 12
CA 02800186 2012-12-28 ,
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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
_ _
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
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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
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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 -- --
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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
0
1
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
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CA 02800186 2012-12-28
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34 N/A -11.2
38 N/A -8.0
39 +9.5 +2.5
40 -3.7 N/A
1
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%).
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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.
13
14
=
22313576.1 18
