Age-related macular degeneration (AMD) is a leading cause of blindness that results from thickening of Bruch's membrane with age, interfering with metabolism in the retinal pigment epithelium (RPE) and photoreceptors. This causes deposits called drusen that damage the overlying RPE and underlying tissue. There are two forms: dry AMD involves gradual RPE and photoreceptor atrophy, while wet AMD features choroidal neovascularization that leaks fluid and blood, causing rapid vision loss if untreated. Risk factors include age, genetics, smoking, and diet.

1. Age-Related Macular Degeneration Dr Charlotte Hazel

2. Introduction Leading cause of blindness in the Western World Common in Caucasian populations Bilateral disease 60% bilateral within 5 years of visual loss in first eye Earliest signs rarely visible before 45 years.

3. Anatomy Macula Diameter 5 mm 4 mm temporal, 0.8 inferior to optic disc Fovea Depression of ~1 disc diameter (1.5 mm) at centre of macula

4. Anatomy Foveola Central point of fovea 0.35 mm in diameter Thinnest part of retina Cones only High levels of visual acuity

5. Anatomy Choroid RPE Foveola

6. Anatomy

7. Definitions Two forms: Non-exudative (dry) Most common (90%) Geographic atrophy Exudative (wet) Neo-vascularisation Causes more devastating and sudden vision affects

8. Pathophysiology Progressive thickening of Bruch’s membrane with age Interferes with RPE - photoreceptor metabolism Metabolites from photoreceptors accumulate on Bruch’s membrane Like debris!

9. Pathophysiology Drusen (colloid bodies) Earliest clinical sign Lipid or collagen rich deposits (waste) Lie between Bruch’s membrane and RPE Further disruption of RPE/photoreceptor metabolism Cause variable amount of depigmentation and eventually atrophy of overlying RPE

10. Pathophysiology Drusen Bruch’s Membrane RPE Photoreceptors Choroid

11. Pathophysiology Hard Drusen Small localised collection of hyaline material within or on Bruch’s membrane Sharp, well demarcated boundaries Soft Drusen Involve overlying focal RPE detachment Poorly demarcated boundaries Larger/commonly become confluent

12. Hard Drusen

13. Soft Drusen

14. Pathophysiology Drusen Can become calcified (glistening appearance) Can become confluent – representing widespread RPE abnormality Increase risk of vision loss! Can be inherited as a dominant trait Hard Drusen No progression / consequence

15. Confluent Drusen

16. Calcified Drusen

17. Pathophysiology RPE degeneration, seen as: Focal areas of hypo- and hyper- pigmentation (‘stippling’) Eventually areas of atrophy of the RPE revealing underlying choriocapillaris ‘ Geographic atrophy’ = end stage

18. RPE Degeneration

19. RPE Degeneration

20. Summary Age-related thickening of Bruch’s membrane Interferes with photoreceptor/RPE metabolism Causing deposition of metabolites / formation of drusen Damage to overlying RPE/photoreceptors and underlying choriocapillaris

21. Non-Exudative AMD Gradual mild to moderate impairment over months or years Cause: Slow/progressive atrophy of RPE and photoreceptors or Collapse of an RPE detachment overlying soft drusen Advanced form = Geographic Atrophy

22. Geographic Atrophy (GA) Clinical Features: Soft drusen present in early stages (significant risk factor for GA – due to RPE detachment) Decreased retinal thickness and increased visualisation of choroidal vessels Sharply demarcated pale area Choroidal vessels sometimes white

23. Geographic Atrophy (GA)

24. Geographic Atrophy (GA)

25. Geographic Atrophy (GA) Signs/Symptoms: Marked decrease VA (unless foveal sparing) Central field loss (positive scotoma) Difficulty recognizing faces Difficulty reading if large scotoma Difficulties in dim light / adapting

26. Exudative AMD Clinical Features: Choroidal neo-vascularisation Exudative detachment of RPE and/or retina Disciform scar

27. Choroidal Neovascularisation Proliferations of fibrovascular tissue from choriocapillaris through defects in Bruch’s membrane Sub-RPE or sub-retinal Membranes have a greyish/green or pinkish/yellow hue in late stages

28. Choroidal Neovascularisation Tendency to leak Serous and blood Distorted or blurred vision Red if sub-retinal, darker if sub-RPE Rarely vitreous haemorrhage Cause RPE and retinal detachments

29. Choroidal Neovascularisation Fibrous tissue proliferation – scar development (Disciform scar) Permanent vision loss Further bleeding risk of exudative retinal detachment

30. Choroidal Neovascularisation RPE Bruch’s Membrane Photoreceptors Choroid

31. Choroidal Neovascularisation

32. Choroidal Neovascularisation

33. Choroidal Neovascularisation

34. Disciform Scar

35. Investigation History Gradual change = non-exudative Sudden change = exudative Difficulties reading/recognising faces Difficulties with changing light / adapting after bright light (remember when assessing!) Distortion = exudative change!

36. Investigation

37. Investigation Visual acuity Distance and near No improvement (worse?) with pin-hole Amsler-grid Field test for central 20 degrees Show scotoma/distortion Monocular/ correct add for WD! No varifocals/bifocals!!!!

38. Amsler Chart

39. Amsler Chart

40. Amsler Chart

41. Investigation Fundus Examination Binocular view – detect elevation VOLK or contact lens

42. Management Urgent refer any suspected neovascular membrane or sub-retinal fluid Fluorescein angiography Absence of previous drusen – sub-retinal fluid(?) Non-exudative – no surgical treatment

43. Mx. Non-exudative Advice and support Likely to progress Central vision only Advice re. Lighting High add or LVA’s

44. Mx. Non-exudative Amsler Chart – self monitoring Low Vision referral Daily living skills LVA’s Eccentric fixation training? Registration Social Service - advice and benefits

45. Mx. Exudative Argon laser photocoagulation Extrafoveal/Juxtafoveal CNV Subfoveal? Immediate loss of VA Slow progression NOT improve Possible recurrence (up to 50%)

46. Fluorescein Angiography CNV Pre- and Post- Laser Tx CNV Pre-Laser CNV Post-Laser

47. Laser Scars

48. Recurrence

49. Mx. Exudative Photodynamic therapy Photosensitizer dye accumulates in proliferating tissues damaged by appropriate wavelength light More specific than laser – only destroys tissue with photosensitive dye High cost!!

50. Mx. Exudative Radiation Therapy Not conclusive Surgical translocation Still experimental Membrane removal Suitable for young not old RPE transplantation?

51. Risk Factors Fair skin/blue eyes Female Obesity Hypertension High-fat diet / High cholesterol Long-sighted

52. Risk Factors Smoking Accelerate development of ‘wet’ form - twice the risk Sunlight short wavelengths accelerate degeneration History of out-door life Sunglasses/polaroids?

53. Prevention Supplements Carotenoid pigments – green leafy vegetables Zinc – mixed results Anti-oxidants – Vit A and C (particularly combined with Zinc) Selenium Problems with side-effects

54. Prevention Age-Related Eye Disease Study (AREDS) 2001 Vit C 500mg Vit E 400 mg Vit A – 15 mg Zinc – 80 mg (Copper – 2mg) Did not help early stages; reduced risk of progression to advanced forms.

55. Prevention US$ 68.95 per 500ml bottle

56. References www. rcophth .ac. uk /publications /guidelines/ armd .html Mx, prognosis, aetiology etc Kanski, Clinical Opthalmology Various ophthalmology textbooks or atlases Berger et al. Age-related macular degeneration