Download Diabetic Macular Edema (DME)

Media Fact Sheet
Diabetic
Macular Edema
What is diabetic macular edema (DME)?
Diabetic macular edema (DME) is a consequence of diabetic retinopathy, the
most common diabetic eye complication. DME is characterized by abnormal
changes in the blood vessels of the retina, which is the light-sensitive layer
at the back of the eye. In patients with DME, leakage from these abnormal
blood vessels occurs in the central portion of the retina, called the macula.
Because this part of the eye is responsible for sharp central vision, DME can
lead to significant visual impairment. Visual impairment due to DME affects
approximately 1–3% of patients with diabetes, and DME is a leading cause of
blindness in the working-age population in most developed countries.1
What causes DME?
DME is caused by leakage of fluid from the small blood vessels in the eye.5 An
increased expression of vascular endothelial growth factor (VEGF) can escalate
the leakage and vascular permeability.6 The build-up of fluid causes swelling and
thickening in the central portion of the retina (macula), leading to distorted vision.7
The figures below illustrate the effects of vision loss that patients with visual
impairment due to DME may experience compared with a person with normal vision
How serious is DME?
DME is a leading cause of blindness in the working-age population in most
developed countries.2
DME can lead to significant visual impairment in approximately 1–3% of
patients with diabetes.3 For patients, visual impairment is one of the most
feared complications of diabetes.4
The vision loss associated with this ophthalmologic complication of
diabetes can reduce a person’s quality of life and limit daily activities, such
as working, driving, managing medications and social interactions. If left
untreated, DME can lead to blindness.
DME can lead to
significant
visual
impairment
DME is a leading cause of blindness in the working-age population in
most developed countries
An increased
expression of vascular
endothelial growth
factor (VEGF) can escalate the
leakage and vascular
permeability
Normal vision
DME impaired vision
What are the symptoms of DME?
Blurred vision is the most common presenting symptom of DME. Patients with
vision loss associated with DME may also experience image distortion, floaters,
an altered sensitivity to contrast, photophobia, changes in color vision and
scotomas (localized defects of the visual field).
Who is at risk of developing DME?
Visual impairment due to DME is a disabling condition that affects a subset
of patients with diabetic retinopathy.
Diabetes patients with a poor control of blood sugar and blood pressure are
at an increased risk of developing diabetic retinopathy. The risk of developing
DME is closely associated with the length of time a patient has lived with
diabetes and the severity of diabetic retinopathy.8
Novartis Pharma AG
CH-4002 Basel, Switzerland
© 2014 Novartis Pharma AG
Media Fact Sheet
Diabetic
Macular Edema
What is the burden of visual impairment?
The burden associated with visual impairment is the seventh highest
worldwide, accounting annually for more than 55 million disability-adjusted
life-years.9,10
Visual impairment due to DME can negatively impact a patient’s visual
functioning and overall health-related quality of life (HRQoL); generally, a
patient’s perception of their HRQoL worsens as vision health decreases.11
The standard medical costs associated with the treatment of visual impairment
due to DME include hospitalizations, visits to ophthalmologists and the use
of medical devices. Per-patient, direct medical costs associated with DME are
substantially higher than those associated with diabetic retinopathy.12,13
The standard medical costs
associated with the treatment of
visual impairment due to DME
include hospitalizations, visits to
ophthalmologists and the use of
medical devices
€9,214 million in Germany
to more than
Cost of DME
Besides the quality of life burden on DME patients and their caregivers, there
is also a significant cost to healthcare systems and society. Cost components of
visual impairment in the DME community include lost productivity and income
from absenteeism at work, the cost of social services for the blind and visually
impaired, and hospital expenditures resulting from falls and fractures due to
visual complications.
The burden associated
with visual impairment
is the seventh highest
worldwide
There are also significant non-medical costs related
to visual impairment. In Europe, the total annual non-medical expenditure for people with visual impairment has been estimated to range from
While laser therapy
can provide
stabilization of
vision in most
patients,
it generally does not restore sight
€15,000 million in the UK
14
How is DME treated?
Intravitreal steroids (e.g. fluocinolone acetonide) are occasionally used in the
management of DME. However, treatment is associated with safety concerns
such as an increased risk of raised intraocular pressure and the development
of cataracts.17 These adverse events cause the patient to require further
invasive treatments, including cataract surgery.
The previous standard of care for DME was laser therapy, although treated
patients could still experience vision loss.16 The principal goal of laser
therapy is to stop the progression of the disease and stabilize current visual
acuity. While this therapy can provide stabilization of vision in most patients,
it generally does not restore sight.17
Unmet need
There was a substantial unmet need in DME management because of the
limitations of laser therapy. These limitations include:18
A reduction but not elimination in the risk of progression of vision loss,
with approximately 25% of patients experiencing vision loss at 3 years.
Risks associated with permanent damage to the retina caused by laser
treatment include blind spots and secondary choroidal neovascularization.
A significant number of patients with DME remain refractory to laser treatment.
Novartis Pharma AG
CH-4002 Basel, Switzerland
© 2014 Novartis Pharma AG
Media Fact Sheet
Diabetic
Macular Edema
Lucentis
(ranibizumab), is
the only approved
anti-VEGF
pharmacotherapy for
the treatment of vision
loss due to DME
®
Lucentis
provides
superior gains in visual
acuity in patients with
visual impairment due
to DME compared with
standard laser therapy
or sham treatment
Meeting the unmet need with Lucentis
Lucentis® (ranibizumab), the only approved anti-VEGF (vascular endothelial
growth factor) pharmacotherapy for the treatment of vision loss due to DME, is a
humanized therapeutic antibody fragment (Fab) designed to block all biologically
active forms of VEGF-A. It has been developed specifically for use in ocular disease.
Lucentis can be used as an effective monotherapy or as a convenient add-on
therapy to laser therapy for the treatment of visual impairment due to DME.19
For visual impairment due to DME, treatment is given monthly until maximum
stable visual acuity is achieved. If vision loss due to DME recurs, monthly
treatment is resumed until vision is stabilized again (with defined stopping
criteria). The basis of this individualized regimen is maximizing visual outcomes
for each individual patient whilst minimizing the risks of over- or under-treating.
The experience with Lucentis in the treatment of DME has demonstrated that
injection frequency is reduced in subsequent treatment years; 2–4 injections in
the second year and 1–3 in the third year.20,21,22
Efficacy23,24,25
Lucentis provides superior gains in visual acuity in patients with visual
impairment due to DME compared with standard laser therapy or
sham treatment.
There is a rapid onset of effect after the first Lucentis injection.
Lucentis significantly reduces central retinal thickness in DME patients.
Lucentis is the only anti-VEGF agent for which improvement in patient-related
visual function outcomes has been reported.26
Safety Profile
Intravitreal injection of Lucentis has an acceptable ocular safety and tolerability
profile in patients with visual impairment due to DME versus control.
Lucentis has a comparable safety profile in DME patients to that reported for
patients with wet age-related macular degeneration treated with Lucentis.
Adverse events
The most common adverse events with Lucentis treatment in patients
with DME include, increased intraocular pressure, headache, joint pain,
nasopharyngitis and certain eye disorders (such as eye irritation, dry eye and
vitreous floaters), anemia, anxiety, allergic reactions, hypersensitivity, nausea
and urinary tract infection.
An expert panel developed evidence-based treatment recommendations for the
treatment of DME based on 1- and 2-year clinical trial findings for Lucentis,
a treatment they reported can improve visual acuity in DME patients. The
recommendations stated that “DME with or without visual impairment should be
considered for treatment when it fulfils the Early Treatment Diabetic Retinopathy
Study (ETDRS) criteria for clinically significant edema. For DME with center
involvement and associated vision loss due to DME, monthly Lucentis
monotherapy with treatment interruption and re-initiation based on visual
acuity stability is recommended. Laser therapy based on ETDRS guidelines
is recommended for other forms of clinically significant DME without centre
involvement or when no vision loss has occurred, despite center involvement”.27
Learn more about DME here: http://www.youtube.com/watch?v=XgDyqKnIsEM
References
1Saaddine JB, et al. Projection of diabetic retinopathy and other major eye diseases among people with diabetes mellitus. United States,
2005-2050. Archives of Ophthalmology. 2008;126:1740-1747.
2Ciulla TA, et al. Diabetic retinopathy and diabetic macular edema. Diabetes Care. 2003;26:2653-2664.
3Data on file. Novartis Pharma AG, Basel, Switzerland.
4Watkins PJ. Retinopathy. The British Medical Journal. 2003;326:924-926.
5Ferris FL, et al. Macular edema. A complication of diabetic retinopathy. Survey of Ophthalmology. 1984;28:452-461.
6Nguyen QD, et al. Vascular endothelial growth factor is a critical stimulus for diabetic macular edema. American Journal of Ophthalmology.
2006;142:961-969.
7Acharya RU, et al. The Human Eye. In: Image Modeling of the Human Eye. Acharya RU, Ng EYK and Suri JS (Eds.) Norwood, MA: Artech House; 2008.
8Klein R, et al. The Wisconsin epidemiologic study of diabetic retinopathy. IV. Diabetic macular edema. Ophthalmology. 1984;91:1464-1474.
9Chiang PP, et al. Global burden of disease and visual impairment. Lancet. 2006;368:365.
10Lopez AD, et al. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006;367:1747-1757.
11Davidov E, et al. Diabetic retinopathy and health-related quality of life. Graefe’s Archive for Clinical and Experimental Ophthalmology. 2009;247:267-272.
12Happich M, et al. The economic burden of diabetic retinopathy in Germany 2002. Graefe’s Archive for Clinical and Experimental Ophthalmology.
2008;246:151-159.
13Shea AM, et al. Resource use and costs associated with diabetic macular edema in elderly persons. Archives of Ophthalmology. 2008;126:1748-1754.
14Lafuma A, et al. Evaluation of non-medical costs associated with visual impairment in four European countries: France, Italy, Germany and
the UK. Pharmacoeconomics. 2006;24:193-205.
15Martidis A, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Ophthalmology. 2002;109:920-927.
16Bhagat N, et al. Diabetic macular edema: pathogenesis and treatment. Survey of Ophthalmology. 2009;54:1-32.
17American Academy of Ophthalmology Retina Panel. Preferred Practice Pattern® Guidelines. Diabetic Retinopathy. San Francisco, CA:
American Academy of Ophthalmology; 2008. Available at: http://www.aao.org/ppp
18Chun DW, et al. A pilot study of multiple intravitreal injections of ranibizumab in patients with center-involving clinically significant diabetic
macular edema. Ophthalmology. 2006;113:1706-1712.
19Lucentis European Summary of Product Characteristics. European Medicines Agency 2011.
20The Diabetic Retinopathy Clinical Trial Research Network. Randomized trial evaluating ranibizumab plus prompt laser or deferred laser or
triamcinolone plus prompt laser for diabetic retinopathy macular edema. Ophthalmology 2010;117:1064-1077.
21The Diabetic Retinopathy Clinical Trial Research Network. Intravitreal Ranibizumab for Diabetic Macular Edema with Prompt versus Deferred
Laser Treatment: Three-year randomized trial results. Ophthalmology 2012;119:2312-2318.
22Schlingemann RO, Lanzetta P, Massin P, Gerstner O, Bouazza AS, Shen H, Osborne A, Mitchell P; et al. the RESTORE extension study group.
Three-Year Outcomes of Individualized Ranibizumab Treatment in Patients with Diabetic Macular Edema: The RESTORE Extension Study.
Ophthalmology. 2014 Feb 1. pii: S0161-6420(13)01167-6.
23Data on file. Novartis Pharma AG, Basel, Switzerland.
24The Diabetic Retinopathy Clinical Research Network. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone
plus prompt laser for diabetic macular edema. Ophthalmology. 2010;117:1059-1060.
25Wolf S, et al. Safety and efficacy of ranibizumab treatment in patients with diabetic macular edema: 12-months results of the RESOLVE study.
Investigative Ophthalmology and Visual Science. 2009;50:E-Abstract 4331.
26Mitchell P, et al. RESTORE Study Group. Patient-reported visual function outcomes improve after ranibizumab treatment in patients with
vision impairment due to diabetic macular edema: randomized clinical trial. JAMA Ophthalmol. 2013;131(10):1339-47.
27Bandello F, et al. New approaches for the treatment of diabetic macular oedema: recommendations by an expert panel. Eye. 2012;
doi:10.1038/eye. 2011.337.
Novartis Pharma AG
CH-4002 Basel, Switzerland
© 2014 Novartis Pharma AG