Age-related macular degeneration (AMD) affects the choroid, RPE and outer retinal layers. The condition is divided into non-exudative/dry and exudative/wet. Early detection of exudative AMD is essential to prevent permanent vision loss. The goal of the eye care provider is to detect early CNVM before subretinal fibrosis develops leading to scarring and irreversible damage to the outer retinal layers.
OCT has revolutionized our ability to detect early choroidal neovascular membranes (CNVM) in exudative/wet AMD. The instrument is also used to track response to treatment in anti-vascular endothelial growth factors (VEGF) therapies. The Comparison of AMD Treatment Trials (CATT) study utilized TD-OCT and SD-OCT to track the response of Avastin versus Lucentis treatment.
Non-exudative/Dry AMD
Drusen can appear hyper-reflective with some areas of hypo-reflectivity within the lesion depending on the composition of the drusen. Bruch's membrane can be visible because the drusen is located between the RPE and Bruch's membrane. Drusen can push on the RPE causing the RPE to appear irregular, thinner and disrupted. The IZ line and EZ line can be elevated with the RPE and can become disrupted as the condition progresses corresponding to a loss in visual acuity.
Figure 1. Non-exudative AMD with large drusen. Mild disruption of the EZ line is visible. No signs of subretinal fluid or CNVM. Foveal contour is intact.
Figure 2. Non-exudative AMD with large drusen.
Drusenoid pigment epithelial detachment (DPED)
The AREDS Report number 28 defined pigment epithelial detachments as well-defined drusen at least 350 microns in the narrowest diameter and appears elevated on stereoscopic fundus photographs. A DPED has a high rate of progression to both geographic atrophy (GA) and neovascular AMD.
Figure 3. Drusenoid pigment epithelial detachment (DPED).
Figure 4. Drusenoid pigment epithelial detachment (DPED) with RPE migration.
Drusen regression
Drusen can increase in size and number as the condition progresses. However, Gass first noted that drusen could also fade and disappear leaving only an irregular mottling of the RPE. When drusen regresses visual acuity (VA) could remain unchanged or it could be a sign of progression towards geographic atrophy.
Figure 5. Regression of drusen over 8 months. Vision decreased by 1 line. Note the difference in the RPE layer map. These scans were acquired with the Cirrus SD-OCT 512x128 macular cube scans utilizing the macular change analysis.
Geographic atrophy
As non-exduative AMD progresses in more advanced stages, the outer retinal layers become disrupted and develops atrophy. Drusen is reabsorbed and geographic atrophy develops that corresponds to decrease in central vision. SD-OCT scans of geographic atrophy reveals RPE thinning, loss of EZ and IZ lines, depression of the inner retinal layers as the outer layers are loss, and increase visibility of Bruch's membrane and the choroid.
Figure 6. SD-OCT horizontal scan over the fovea in a patient with non-exudative AMD with geographic atrophy. There is loss of outer retinal layers including the RPE, EZ, IZ, ELM, and the outer nuclear layer. The Bruch's membrane and choroidal capillaris is visible due to the overlying outer retinal atrophy.
Figure 7. SD-OCT horizontal scan over the fovea in a patient with non-exudative AMD with subfoveal geographic atrophy. There is loss of outer retinal layers including the RPE, EZ, IZ, ELM, and the outer nuclear layer. The Bruch's membrane and choroidal capillaris is visible due to the overlying outer retinal atrophy.
Other changes visible on SD-OCT in AMD:
Retinal pigment migration
Pseudocysts
Outer retinal tubulation
Small subretinal fluid/space between large drusen
Acquired vitelliform lesion (AVL) associated with large drusen
Figure 8: Outer retinal tubulation in a patient with nonexduative age-related macular degeneration.
Figure 9: Pseudocysts in a patient with nonexduative age-related macular degeneration. The hyporeflective space does not indicate a CNVM but a degenerative process.
Figure 10: Pseudocysts in a patient with non-exduative age-related macular degeneration.
Figure 11: Pseudocyst in a patient with non-exduative age-related macular degeneration. The hyporeflective space does not indicate a CNVM but a degenerative process.
Pseudocysts can be seen on SD-OCT as a hyporeflective circular shaped lesion. This retinal finding is seen in retinal degenerative conditions and is common in atrophic age-related macular degeneration. Pseudocysts can be mistaken as intraretinal edema secondary to leakage from a choroidal neovascular membrane (CNVM). However, pseudocysts do not leak on fluorescein angiography. They are believed to correspond to Muller cell degeneration, as suspected in idiopathic juxtafoveolar retinal telangiectasis type 2A.
Figure 12: Acquired vitelliform lesion (AVL) associated with large drusen.
Exudative/Wet AMD
Early exudative AMD can be difficult to detect on ophthalmoscopy and on stereographic photographs. In early stages only mild elevation is present secondary to subretinal fluid (SRF) leakage in areas of RPE mottling. SD-OCT can detect early SRF and even identify the layers involved in a CNVM. Fluorescein angiography is required sometimes in early cases to confirm the diagnosis of a CNVM if not apparent on fundus evaluation.
Figure 13. Classic/Type 2 CNVM located above the RPE with SRF adjacent to the lesion. A few exudates are visible on the nasal side of the lesion.
CNVM can classified according to their location in relation to the RPE, location in relation to the fovea and based on fluorescein angiography findings.
Type 1 or occult CNVM appears beneath the RPE layer and appear as a fibrovascular or hemorrhagic pigment epithelial detachment.
Type 2 or classic CNVM appears above the RPE layer and adjacent SRF leakage.
Figure 14. Fibrovascular pigment epithelial detachment secondary to a CNVM. Hyper-reflective material is visible in the PED. Type 1.
Other examples of CNVM SD-OCT scans:
Figure 15. Fibrovascular pigment epithelial detachment secondary to a CNVM. Small amount of SRF is visible adjacent to the CNVM. Type 1.
Figure 16. CNVM in false color code. Subretinal fluid and intraretnal fluid is visible. When the CNVM leaks it will start in the subretinal space and may leak into the intraretinal layers.
Other types of occult CNVM includes retinal angiomatous proliferation (RAP) and polypoidal choroidal vasculopathy (PCV).
Retinal angiomatous proliferation (RAP)
RAP is described as type 3 CNVM. RAP involves 3 stages. Stage 1 consist of intraretinal neovascularization and as the intraretinal neovascularization grows it extends posteriorly forming stage II subretinal neovascularization. Finally, in stage III the condition develops into a vascularized PED.
Polypoidal choroidal vasculopathy (PCV)
PCV is a the condition that generally affects darker pigmented individuals and has a higher incidence involving Asians and African Americans. The condition is commonly misdignosed as exudative age-related macular degeneration. The etiology is not well understood but it has been proposed that there are abnormal choroidal vasculature with dilation and aneurysmal formation. Patients will present with subretinal, vascular lesions associated with serous and hemorrhagic PEDs around the peripapillary area.
ICGA is standard for diagnosis of polypoidal lesions. Treatment includes combination therapy of photodynamic therapy (PDT) and anti-VEGF therapy.
For more information on treatment read the EVEREST trial.
Suggested readings:
AREDS Report #8- http://www.ncbi.nlm.nih.gov/pubmed/11594942
AREDS 2- http://www.ncbi.nlm.nih.gov/pubmed/23644932
CATT study- http://www.ncbi.nlm.nih.gov/pubmed/22555112
VIEW 1 & 2- http://www.ncbi.nlm.nih.gov/pubmed/24084500
MARINA, ANCHOR, PRONTO, IVAN, HARBOR