Cotton Wool Spots

Local infarct of the Nerve Fiber Layer.

Soft Drusen

Primary Causes
Hypertension (#1 cause)
Systemic Lupus Erythematosus (SLE)

Rare Causes
Hyperviscosity syndromes (Multiple Myeloma, Waldenstrom Macroglobulinemia)

Hypercoagulability syndromes (Factor V Leiden, Prothrombin 20210A, Hyperhomocysteinemia, Protein S/C deficiency, Antithrombin III deficiency, Dysfibrinogenemia, Factor XII deficiency)

Carotid/Cardiac Emboli (from high cholesterol, mitral valve disease)
Purtscher's Retinopathy (Multiple CWS with sudden vision loss)
Rocky Mountain Spotted Fever
Cat Scratch Fever
Onchocericiases (River Blindness)
Interferon Therapy
Metastatic Carcinoma
Dermatomyositis (rash + muscle pain)
Polyarteritis Nodosa
Giant Cell Arteritis (GCA)
Epiretinal Membrane
Traumatic NFL laceration (lesion will not resolve)
Long Bone Fractures
Radiation Retinopathy
Bacterial/Fungal Infections

Usually resolves within 8-10 weeks.  Underlying cause of ischemia could cause new cotton wool spots to appear in unpredictable locations at unpredictable times. 

Associated Symptoms
Cotton wool spots are an indication of ischemia to the retina, which could indicate ischemia to other parts of the body.  They could be a precursor to stroke, heart attack, etc.

Primary Workup
Sphygmomanometry (High Blood Pressure)
FBS/HbA1C  (Diabetes)
ANA (SLE, Scleroderma)
HIV antibody test (HIV)
CBC w/ platelets and differentials (Anemia, Hyperviscosity)

Second Line Workup (If primary test results all  negative)
Various tests for Hypercoagulability
Carotid Doppler with 2D Echo (Carotid Artery Disease)
EKG (Cardiac Function)
Chest Radiography/CT/MRI (Rocky Mountain Spotted Fever - only if patient is also ill)
CSD skin-test antigen (Cat Scratch Disease)
Blood culture (Leukemia, Lymphoma, Infections)
ESR, CRP (GCA, Polyarteritis Nodosa)
Tests for various cancers (metastatic carcinoma)
Investigate causes for Purtscher's (if multiple CWS)
Treat the underlying cause