- ARMD = Age Related Macular Degeneration
- wet ARMD = neovascular ARMD with CNV
- CNV = choroidal neovascularisation
- GA = geographic atrophy
Wet ARMD has a substantial genetic component (Nottingham 2011) see
This pathway accounts for 92% of the genetic component of wet ARMD. This is much more common in women, as the men die early. The CNV develop average age 78, the GA about 5 years later.
|ARMS2 / HtrA / (PLEKHA1)|
|vascular changes in the choroid due to lack of perfusion|
|reticular drusen/ pseudodrusen (these are vascular changes in the choroid, which appear as RPE changes on the OCT (but this is an artefact...the changes are in the choroid) risk|
|Geographic atrophy, lobulated type|
|CNV / wet ARMD|
In the last 5 years we have learnt the most important genes that affect ARMD. Many influence the complement pathway. For many years drusen have been shown to contain a lot of complement-like material, and now we know the main genes are involved in complement.
Complement is a protein in blood, used as part of the clotting mechanism. In this respect ARMD should be considered as a systemic disease. diagram diagram Patel's paper is very detailed and has many references. Here are some of the compliment genes
The complement pathway is key in such functions as fighting infection. But it is also involved in ARMD. In dry ARMD it is found in drusen, and various studies of wet show a relationship.
Seddons model and others
09 11 has
worked out the relevant risks of each gene, and these will soon be
used to calculate each person's risk. Seddon 11
" In multivariate models, age, smoking, body mass index, single nucleotide polymorphisms in the CFH, ARMS2/HTRA1, C3, C2, and CFB genes, as well as presence of advanced AMD in 1 eye and drusen size in both eyes were all independently associated with progression."
|Risk factors used in Seddons 09 model|
"The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. "