Neovascular Age-Related Macular Degeneration

The characteristic of neovascular AMD is the ingrowth of CNV from the choriocapillaris under the macular region (Figure 5).

Figure 5: Neovascular age-related macular degeneration. A, The patient had choroidal neovascularization followed by numerous episodes of hemorrhage, resulting in an organized scar. B, A

small vessel (C, capillary) has grown through Bruch's membrane (B) into the sub–retinal pigment epithelial space, resulting in hemorrhage and fibroplasia. C, The end stage shows a thick, fibrous scar between the choroid and the outer retinal layers (trichrome stain). Note the preservation of the retina, except for complete degeneration of the photoreceptors (B, Bruch's membrane; C, choroid; NR, neural retina; S, sclera; ST, scar tissue).

The potential clinical manifestations of Neovascular Age-related Macular Degeneration are indicated in the table above:

Potential Clinical Manifestations of Neovascular AMD Plaque-like membrane or gray or yellow-green discrete discoloration Subretinal fluid

Macular edema

Retinal, subretinal, or sub-RPE hemorrhage Retinal or subretinal lipid exudate

Retinal pigment epithelial detachment RPE tear

Subretinal fibrosis or disciform scar

Associated features of non-neovascular AMD, including drusen, RPE atrophy, and focal pigmentary changes, are typically present in eyes manifesting CNV, as well as fellow eyes. However, CNV secondary to AMD may occur without any of these precursor lesions; if they are not present, other possible causes of CNV must be evaluated. [153]

The non-macular peripheral CNV is developed in patients affected by AMD, especially in their temporal retina. Postequatorial subretinal hemorrhage and fluid accumulation are, occasionally, the results in such lesions. Although, these peripheral disciform detachments may lead to breakthrough vitreous hemorrhage, they rarely require therapy.[154]

3.3.1 Retinal Pigment Epithelial Detachment: Fibrovascular tissue, hemorrhage, serous fluid, or coalescence of drusen beneath the RPE may cause retinal pigment epithelial detachment (PED). Each has a unique clinical appearance and represents specific pattern of fluorescence on angiography. Fibrovascular PED represents a type of occult

CNV. Hemorrhagic PED manifests as a dark elevation of the RPE due to underlying blood, showing blocked fluorescence throughout all phases of angiography. Serous PED appears as a dome-shaped detachment of the RPE, exhibiting bright diffuse hyperfluorescence with progressive pooling in a fixed space. Drusenoid PED, caused by coalescence of drusen, shows staining, often with fading fluorescence in the late phase and an absence of leakage.[154]

3.3.2 Fluorescein Angiography: Fluorescein angiography is a useful diagnostic method in all patients with CNV. It determines the characteristics of the lesion and it directs and modifies the therapeutic modalities. In eyes that have drusen or geographical atrophy without any new symptom or no clinical evidence of neovascularization, its contribution as a screening test, is of no importance. Determination of the presence of CNV and evaluation of the extent, location, and composition of its components are critical in deciding whether treatment is indicated and, if so, which therapeutic modality is appropriate.[155-158] As the new treatments that are developed have specific criteria for their effective utilization, it is becoming increasingly important to determine in details the characteristics of the CNV.

If a lesion is well demarcated, its location may be determined by the closest point to the center of the foveal avascular zone (FAZ). Lesion location is classified angiographically as follows:

• Extrafoveal (≥200µm and <2500µm from the center of the FAZ).

• Juxtafoveal (1–199µm from the center of the FAZ).

• Subfoveal (under the center of the FAZ).

3.3.3 Choroidal Neovascularization: CNV represents new blood vessel growth from the choriocapillaris through a degenerated Bruch's membrane. Based on angiographic patterns of fluorescence, components of CNV lesions may be categorized as either classic or occult (Figure 6).

Figure 6: Neovascular age-related macular degeneration. A1–A2, Fluorescein angiography of classic

choroidal neovascularization showing early, bright, uniform hyperfluorescence with leakage in the late frame. B1–B2, Fluorescein angiography of occult choroidal neovascularization (fibrovascular pigment epithelial detachment) showing stippled hyperfluorescence in the earlier frame and late leakage. C1, Fluorescein angiography of a serous pigment epithelial detachment showing pooling within a fixed sub–

retinal pigment epithelial cavity. C2, Optical coherence tomography cross-section demonstrates a dome-shaped elevation of the retinal pigment epithelium by a hyporeflective (serous) fluid collection.

Classic CNV is characterized by bright, uniform, early hyperfluorescence exhibiting leakage in the late phase and obscuring the boundaries. Occult CNV is recognized angiographically by one of two patterns: fibrovascular PED, or late leakage from an undetermined source.

With the introduction of digital imaging systems, the use of indocyanine green (ICG) angiography in AMD has been evaluated. The dye's characteristics enable this mode of angiography to delineate the choroidal circulation better than fluorescein angiography does. Hence, ICG angiography may be useful for the detection of areas of

occult CNV. The appearance of CNV based on ICG angiography may be categorized into three types [159, 160] focal spots, plaques, and a combination of the two.

Currently, the decision of laser treatment is guided by the ICG angiography findings.

4. Epidemiology

AMD is more common in whites than in Hispanics or Asian persons, whereas blacks have the lowest prevalence of the disease.[161]Data from the Human Genome Project revealed that polymorphisms in the complement factor H (CFH), complement factor B (CFB) and the complement component C2 genes may account for 75% of AMD cases.[162] A polymorphism (Ala69Sr) on the age-related maculopathy susceptibility 2 gene (ARMS2 or LOC387715) has also been strongly associated with development of AMD.[163]

Patients with a history of more than 10 pack-years of smoking have an increased risk for the development of AMD and even passive smokers also appear to have a doubled risk of AMD.[164] Other modifiable risk factors for advanced AMD include arterial hypertension [165],obesity [80], high dietary fat intake [166]and low plasma concentrations of antioxidants and zinc. [167, 168]

5. Treatment

5.1 Treatment for non-exudative age-related macular degeneration