macular degeneration

Introduction

MD is the main cause of legal blindness in Australia, accounting for over 50% of cases and affects 1 in 7 over the age of 50 yrs, of which 17% experience visual impairment, and some 15% of Australians over 80yrs of age have visual loss due to MD
MD is a group of degenerative, progressive and painless retinal diseases that cause progressive loss of central vision
it is usually related to ageing (usually only seen in those over 50yrs of age) in those with genetic predispositions and lifestyle factors
visual impairment may go unrecognised if it is only in one eye - hence the importance of regular testing
appears to have an association with higher Factor H Related Protein 4 (FHR4 protein) levels in the blood FHR4 apparently activates the immune complement system and FHR4 activity appears to be regulated by genes on chromosome 1 - the same genes which are associated with AMD risk ¹⁾
the molecule TLR2 appears to be a critical bridge between oxidative damage and complement-mediated retinal degeneration ²⁾

genetic factors
- 70% of cases have a genetic link
- those with a direct family member with MD have a 50% risk
lifestyle factors
- smoking increases risk 3-4x and makes onset 5-10 yrs earlier than non smokers
- hypertension may be a risk for wet MD
- “healthy nutrition, weight and exercise” may have a role in reducing risk, or at least improving ability to manage the visual impairment affect on lifestyle
  - possible benefits of dietary AREDS based supplements appear to reduce risk by 20-25%
    - oral supplementation with the Age-Related Eye Disease Study (AREDS) formulation (antioxidant vitamins C and E, beta carotene, and zinc) has been shown to reduce the risk of progression to advanced age-related macular degeneration (AMD). Observational data suggest that increased dietary intake of lutein + zeaxanthin (carotenoids), omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA]), or both might further reduce this risk ³⁾
    - AREDS2 formula for daily dosing:
      - 80mg zinc as zinc oxide
      - 500mg vitamin C
      - 400IU vitamin E
      - 2mg copper as cupric oxide
      - 10mg lutein
      - 2mg zeaxanthin

asymptomatic phase
retinal epithelial pigment cells (RPE cells) normally form a layer between the retina and the choroid
MD is characterised by the build up of drusen under the layer of RPE cells and this can be seen on fundoscopy
not everyone with drusen will lose their vision, however, its existence does increase the chance of macular degeneration associated vision loss developing later
currently there are no therapies in this phase that prevent progression apart from lifestyle changes

this occurs when visual impairment commences and can be divided into two forms
dry, atrophic MD
- gradual loss of retinal epithelial pigment cells (RPE cells) and when these cells die there is loss of retina above that area
- currently there are no therapies to reverse this aspect
wet, neovascular MD
- the RPE cells fail to stop choroidal blood vessels from growing through the RPE layer and into the retina
- this results in formation of fragile blood vessels under and within the retina choroidal neovascularisation or CNV
- these can leak fluid or cause haemorrhage and can cause sudden rapid, painless central vision loss
- there is only a 2-4 week window of opportunity to treat these acute events and prevent them causing permanent visual loss and scarring
- Intravitreal injection vascular endothelial growth factor Rx options for wet MD:
  - Lucentis (ranibizumab)
    - an anti-VEGF treatment introduced in Australia in 2007
    - monthly injections ⁴⁾
  - Eylea (aflibercept)
    - an anti-VEGF treatment introduced in Australia in December 2012.
    - dosed monthly or every 2 months after 3 initial monthly doses produced similar efficacy and safety outcomes as monthly ranibizumab ⁵⁾