Mongolian national university of medical sciences Department of ophthalmology Bulganchimeg.B MD

1. Age related
macular
degeneration
1st year of resident,
MNUMS
B.Bulganchimeg MD

2. Macular anatomy

3. Normal aging results
PhotoR
Density &
Distribution
RPE
Melanin granule
Resudial bodies
Progressive
involutional
change

7. Pathogenesis of AMD

8. AMD

9. Classification
AMD
Dry
80-85%
Non
neovascular
Non
exudative
Wet
10-15%
Neovascular
Exudative

12. AMD symptoms

13. Non exudative AMD
• Impairment of vision
• Better in bright light
• Bilateral (Asymmetric)

14. Stage of AMD
Drusen
Incipient atrophy (NGA)
Geographic atrophy

15. Progressive thickening of Bruch’s
memrane with age
Interferes with RPE- photoR
metabolism
Metabolites from
photoRs accumlate
on BM
Lipid, collagen rich deposits
(waste), amyloid, additianal
cellular components

16. Drusen
Small (Hard)
<63µm
Intermediete
63-125µm
Large (Soft)
125µm<

17. Hard drusen

18. Soft drusen

19. Confluent drusen

20. Calcified drusen

21. a.FP soft, confluent, large drusen with dry AMD b. SD-
OCT soft drusen c. FA areas of soft drusen

22. Abnormalities of the RPE

23. RPE degeneration
• Focal area of hyper
pigmentation
• Associated with
progression to late AMD
with visual loss
• GA end stage or late
advanced stage of Dry
AMD

24. Geographic atrophy
• Soft drusen presents
early stage of GA
• Sharply demarcated
pale area
• Retinal thickness
• Choroidal vessels

25. Clinical symptoms
• Decrease VA
• Central scotoma
• Difficulty recognizing
faces & reading
• Difficulty dim/light
adapting

28. Severity classification of AMD by AREDS
1point 1 or more large drusen
1 point any pigment abnormalities
1 point bilateral intermediate drusen (no large drusen)
2 point neovascular AMD
5 and 10 year risk of
Advanced AMD in
one eye
5 year risk % 10 year risk %
0 0.5 1
1 3 7
2 12 22
3 25 50
4 50 67

29. Diagnostic criteria
•Soft drusen >63µm
•RPE abnormalities –areas of
hyperpigmentation
• VA is not a criterian for the diagnosis
Degenerative disorder in
person >50 years

30. Management of dry AMD

31. Age Related Eye Disease Study 1
Prospective Natural History study
Randomized, Multi-center, Double-masked,
Placebo controlled 6 years Clinical Trial (2001),
4757 participantrs with <2% loss to Followed
Up.

32. No AMD
Category 1
No or few small drusen (<63µm)

33. Early AMD
Category 2
Intermediate drusen (63-124µm)

34. Intermediate AMD
Category 3
Large drusen (125>µm)

35. Advanced AMD
Category 4
GA involving the macula

36. AMD staging
AREDS
Category
AREDS Category
1
AREDS Category
2
AREDS Category
3
AREDS
Category 4
AMD
classification
No AMD Early AMD Intermedtiadate
AMD
Advanced AMD
Characteristics No drusen or a
few small drusen
Comnibation of
multiple small
drusen, a few
intermediate
drusen, or mild
RPE
abnormalities
Numerous
intermediate
drusen, at least
1 large drusen,
geographic
atrophy
Neovascular
AMD or
geographic
atrophy
involving center
of the macula

37. Randomized
Participant
N=4757
Placebo
N=1483
Antioxidant
N=1482
Zinc
N=904
Antioxidant
+Zinc
N=888
Age Related Eye Disease Study (AREDS)
Treatment Assignment

38. Antioxidants- Daily oral dose
– Vitamin C 500 mg
– Vitamin E 400 IU
– Beta Carotene 15 mg
(=25000 IU Vitamin A)

39. Zinc treatment- Daily oral dose
• Zinc 80 mg
• Copper 2 mg

40. Rates to advanced AMD

41. Long Term Rates to Advanced AMD

42. AREDS formulation recommended
• Patients with intermediate AMD
(bilateral larger drusen)
• Patients with advanced AMD in one eye
• Not for current smokers !
• AREDS formulation doesn’t prevent
cataract progression or early AMD
progression

43. AREDS formulation adverse effect
• Beta carotene increased the risk of lung
cancer and it associated mortality
• High levels of zinc resulted in increased
hospitalizations for genitourinary causes
(mostly hypertrophy of prostate)

44. Age Related Eye Disease Study 2
Study design
Randomized , Multicenter (82 clinics)
Academic and community centers

45. Inclusion criteria
• Bilateral large drusen or late AMD in one eye
Large drusen GA NV AMD

46. Primary objective
• Lutein/Zeaxanthin
• Omega-3 Long chain polyunsaturated fatty
acid ( DHA & EPA)
• Combination to the AREDS formulation

47. Dietary supplements
• Carotenoids (Xantophylls)
Lutein/Zeaxanthin (L/Z) 10mg/2mg
• Omega-3 Long chain polyunsaturated fatty
acid
Docosahexaenoic acid DHA 350 mg
Eicosapentaenoic EPA 650 mg

48. Randomized
Participant
n=4203
Control
1012
Lutein/Zeax
anthin
1044
DHA/EPA
1068
L/Z+
DHA/EPA
1079
Primary Randomization

49. AREDS formulation
– Vitamin C 500 mg
– Vitamin E 400 IU
– Beta Carotene 15 mg
– Zinc (80 mg ZnO)
– Copper 2 mg (CuO)

50. 2nd randomization AREDS formulation
Vitamin
C
Vitamin E Beta
carotene
Zinc
oxide
Cupric
oxide
1 500mg 400 IU 15 mg 80 mg 2 mg
2* 500mg 400 IU 0 mg 80 mg 2 mg
3 500mg 400 IU 15 mg 25 mg 2 mg
4* 500mg 400 IU 0 mg 25 mg 2 mg
Smokers randomized to treatments without beta-carotene

51. Randomized
Participant
n=3036
AREDS
formulation
659
AREDS
(-) beta
carotene 863
AREDS +
Low zinc
689
AREDS(-) β
carotene+
Low zinc 825
2nd randomization AREDS formulation

52. Comprasion of L/Z vs without L/Z
• Advanced AMD p=0.04
10% additional reduction in the risk of
progression to AAMD with L/Z

53. L/Z plus AREDS minus beta carotene vs
AREDS with beta carotene
• Advanced AMD p=0.02
18% reduction in the risk of progression to
AAMD with L/Z
Neovascular AMD p=0.01
22% reduction the risk of progression to
neovascular AMD with L/Z

54. AREDS 2 formulation
– Vitamin C 500 mg
– Vitamin E 400 IU
– Beta Carotene 15 mg
– Zinc (80 mg ZnO)
– Copper 2 mg (CuO)

57. Exudative AMD

58. PhotoR and RPE send a distress signal to
choriocapillaries to make a new vessels
New vessels grow behind the macula
Break down the BM
Blood vessels are fragile
Leak blood and fluid
Scarring of macula
Potential for rapid severe visual damage

59. Exudative AMD
Clinical features
• CNV
• Exudative RPED
 Sub RPE type 1
Subretinal RPE type 2
• Serous and blood
• Distorted/painless blurred
vision, with
metamorphopsia
• Red-subretinal , dark-sub
RPE
• Rarely VH

65. CNV

67. Management of neovascular AMD
• Laser photocoagulation
• Photodynamic therapy
• Antiangiogenic therapy

68. Ranizumab and Bevacizumab for
Neovascular AMD
Methods: 1208 patients with NAMD
Receive injection monthly/given as needed
Study patients:Feb 2008- Dec 2009, 1208
patients
• Criteria included:
• Age>50 years
• No treatment acute CNV due to AMD
• Fluid/hemorrhage under the fovea

69. Intravitreal
injection
Ranibizumab
monthly
Bevacizumab
monthly
Ranibizumab
given as
needed
Bevacizumab
given as
needed
Treatment

70. Dose
0.50 mg (0.05 ml solution) 1.25 mg (0.05 ml solution)
2000$ 50$

71. Conclusion
• First injection
• Ranizumab- no fluid seen at 4 weeks 27.5%
• Bevacizumab 17.3%
• Ranizumab=Bevacizumab given monthly
• Ranizumab and Bevacizumab given as needed
are best outcomes
• Both injection immediately reduced the
amount of fluid in or under the retina