Transcript Slide 1

Normal Retina
Photoreceptors
Fovea
RPE
Choroid
Macula
A range of visual defects with macular pathology
Neovascular AMD
Neovascular AMD
Distortion
Blur
Scotoma
Normal
DMEDME
Blur
DME with proliferative DR
Blur + scotomas
RISK FACTORS
Age
Smoking
Positive family history
Hypertension
Females
Raised cholesterol
Light iris color
DIET
Vitamins – C 500 mg, E 400 IU
Micronutrients – Zinc 80mg with 2mg
cupric oxide
Beta carotene 15mg – Avoid in smokers
Fish
Nuts
Lifestyle modification
Avoid smoking
Reduce obesity
Use sunglass & Hats
Avoid alcohol
VEGF Inhibition in AMD
FDA approved
Pegaptanib
–
–
Aptamer
Specific for VEGF-A isoform 1651
Ranibizumab
–
–
Recombinant, humanized antibody fragment
Blocks all VEGF-A isoforms
Off label
Bevacizumab
–
–
1Gragoudas
Recombinant humanized monoclonal antibody
Blocks all VEGF-A isoforms
ES, et al. N Engl J Med. 2004;351:2805.
VEGF-A Is a Key Mediator of
Environmental
Angiogenesis
VEGF-A binding and
factors
1
(hypoxia,2 pH)
Growth factors,
hormones1
activation of VEGF
receptor3
(EGF, bFGF, PDGF,
IGF-1, IL-1, IL-6,
estrogen)
ANGIOGENESIS3
Endothelial cell
activation3
Endothelial cell activation,
proliferation, migration4
VASCULAR
LEAKAGE3
VEGF-A = vascular endothelial growth factor A; EGF = epidermal growth factor; bFGF = basic fibroblast
growth factor; PDGF = platelet-derived growth factor; lGF = insulin-like growth factor; IL= interleukin.
1. Dvorak HF. J Clin Oncol. 2002;20:4368. 2. Aiello LP, et al. Arch Ophthalmol. 1995;113:1538.
3. Ferrara N, et al. Nat Med. 2003;9:669. 4. Griffioen AW and Molema G. Pharmacol Rev. 2000;52:237.
VEGF Inhibition in AMD
FDA approved
Pegaptanib
–
–
Aptamer
Specific for VEGF-A isoform 1651
Ranibizumab
–
–
Recombinant, humanized antibody fragment
Blocks all VEGF-A isoforms
Off label
Bevacizumab
–
–
1Gragoudas
Recombinant humanized monoclonal antibody
Blocks all VEGF-A isoforms
ES, et al. N Engl J Med. 2004;351:2805.
Different gold standard diagnostics with
common ancillary tests
Neovascular AMD

Early detection of neovascular
AMD is possible with an
Amsler grid1

FA is essential to confirm
diagnosis of neovascular AMD,
and to identify the location and
composition of the CNV1


DME is diagnosed stereoscopically
as retinal thickening in the macula
using fundus contact lens
biomicroscopy3
Ancillary tests:3
Ancillary tests:2

DME
ICGA – delineation of choroidal
vessel morphology
OCT – measurement of retinal
thickness

FA – identification and evaluation
of fluid leakage from lesions

OCT – measurement of retinal
thickness
1. Sickenberg M. Ophthalmologica 2001;215:247–253
2. The Royal College of Ophthalmologists. AMD: guidelines for management. 2009.
http://www.rcophth.ac.uk/docs/publications/AMD_GUIDELINES_FINAL_VERSION_Feb_09.pdf [accessed Sep 2009]
3. Bhagat N et al. Surv Ophthalmol 2009;54:1–32
Standard of care: improvement with
neovascular AMD vs stabilization with DME
Neovascular AMD

DME
Ocular treatment – Anti VEGFs
IVI1
•
•

Ocular treatment –
laser photocoagulation2–4
•
Maintenance of vision can be
expected in 90–95% of patients
Improvement of vision by
≥3 lines can be expected in
30–40% of patients
•

Rarely provides visual
improvement
In the 1985 ETDRS, VA improved
in 16%, was unchanged in 77%
and worsened in 7% of patients
Systemic treatment4
•
•
•
•
Glucose control
Blood-pressure control
Blood-lipid control
Multifactorial metabolic
interventions
1. Schmidt-Erfurth UM et al. Acta Ophthalmol Scand 2007;85:486–494
2. Bhagat N et al. Surv Ophthalmol 2009;54:1–32
3. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol 1985;103:1796–1806
4. Furlani BA et al. Expert Opin Emerg Drugs 2007;12:591–603
Diabetes and vision loss
Diabetes mellitus (DM) is a prevalent disease. Most
common complications are microvascular changes1
Diabetic retinopathy (DR) is a common microvascular
complication of diabetes2
Diabetic macula edema (DME) is a common cause of
blindness in people of working age2,3 and can develop
in both Type 1 and 2 DM4
About 8% of diabetic patients develop DME with
visual impairment5
1King
et al. Diabetes Care 1998; 21: 1414-1431; 2Royal College of Ophthalmology. Diabetic Retinopathy Guidelines 2005.
http://www.rcophth.ac.uk/docs/publications/publishedguidelines/DiabeticRetinopathyGuidelines2005.pdf. Accessed February 2009;
3Watkins. BMJ 2003; 326: 924-926; 4Klein et al. Ophthalmology 1998; 105: 1801-1815; 5Calculated from: Ling et al. Eye 2002; 16:
140-145; Broadbent et al. Eye 1999; 13: 160-165; Knudsen et al. Br J Ophthalmol 2006; 90: 1404-1409; Hove et al. Acta
Ophthalmol Scand 2004; 82: 443-448; Romero-Aroca et al. Arch Soc Esp Oftalmol 2007; 82: 209-218; Zietz et al.
Dtsch Med Wochenschr 2000; 125: 783-788; Kristinsson. Acta Ophthalmol Scand Suppl 1997; 223: 1-76
DME: the main cause of central
vision loss in DR
DME was shown to affect approximately
10% of the diabetic population
Klein et al. Ophthalmology 1995; 102: 7-16
VEGF165 in DR
Retinal VEGF165
levels are elevated in
experimental diabetes
Increased VEGF165
levels are found in the
vitreous of eyes with
proliferative DR
Patients with DR have
higher VEGF165
levels in the aqueous
Qaum et al. IOVS 2001; 42: 2408-2413; Aiello et al. N Engl J Med 1994; 331: 1480-1487
Factors affecting DME
Incidence of DME increases with
– elevated levels of HbA1C
– severity of DR
– duration of DM
– elevated diastolic blood pressure
– gender (more frequent in females)
– serum lipid levels
Klein et al. Ophthalmology 1998; 105: 1801-1815
DME: current treatment
Systemic treatment
–
–
–
–
glucose control
blood-pressure control
blood-lipid control
multifactorial metabolic interventions
Ocular treatment
– laser photocoagulation (standard treatment for DR /
DME)
– vitrectomy
– pharmacologic therapy
AAO Guidelines. Diabetic Retinopathy. http://www.aao.org/ppp. Accessed February 2009
Royal College of Ophthalmology. Diabetic Retinopathy Guidelines 2005.
http://www.rcophth.ac.uk/docs/publications/publishedguidelines/DiabeticRetinopathyGuidelines2005.pdf. Accessed February 2009
DME: aims of therapy
Reduction in vessel hyperpermeability
and leakage in macular edema
Treatment of neovascularizatio in PDR
Laser photocoagulation for DME
Standard treatment – helps to slow fluid leakage
and reduce the amount of fluid in the retina
(macula edema)
Aim of treatment is to stabilize / prevent further
vision loss
Limitations of treatment include
– does not eliminate possibility of further vision loss
– improvement in visual acuity is uncommon
– complications including permanent damage to the retinal pigment
epithelium and secondary choroidal neovascularization
National Eye Institute, National Institutes of Health. Diabetic Retinopathy.
http://www.nei.nih.gov/health/diabetic/retinopathy.asp#4a Accessed February 2009
AAO Guidelines. Diabetic Retinopathy. http://www.aao.org/ppp. Accessed February 2009
Royal College of Ophthalmology. Diabetic Retinopathy Guidelines 2005.
http://www.rcophth.ac.uk/docs/publications/publishedguidelines/DiabeticRetinopathyGuidelines2005.pdf. Accessed February
2009
DR and DME:
the unmet treatment needs
Despite the use of standard interventions for DR, vision
loss as a result of the disease still occurs in many
patients1
Good metabolic and blood-pressure control are often
difficult to achieve in clinical practice, and sightthreatening DR still develops2
Laser treatment is destructive and cannot restore vision
loss that has already occurred; it therefore cannot be
regarded as an ideal treatment, and there is a need for
better-tolerated and less-destructive therapies3
1Comer
& Ciulla. Curr Opin Ophthalmol 2004; 15: 508-518
2The DIRECT Programme Study Group. J Renin Angiotensin Aldosterone Syst 2002; 3: 255-261
3Fong. Surv Ophthalmol 2002; 47: S238-S245
Intravitreal Ranibizumab
Summary
Intravitreal ranibizumab with prompt or deferred
(≥24 weeks) focal/grid laser had superior VA and
OCT outcomes compared with focal/grid laser
treatment alone.
~50% of eyes had substantial improvement
(≥10 letters) while ~30% gained ≥15 letters
Substantial visual acuity loss (≥10 letters)
was uncommon
Results were similar whether focal/grid laser
was given starting with the first injection or it
was deferred >24 weeks