AGE-RELATED MACULAR DEGENERATION: EXUDATIVE

Age-related macular degeneration (AMD) is the leading cause of legal blindness in people 65 years of age or older in the United States. Approximately 10% of individuals with AMD have the exudative form of the disease. Exudative AMD accounts for the majority of cases of significant visual loss in AMD. Manifestations of exudative AMD may include choroidal neovascularization (CNV), pigment epithelial detachment (PED), retinal pigment epithelial tear, massive subretinal hemorrhage, fibrovascular scar formation, radiating chorioretinal folds, and vitreous hemorrhage.

Symptoms

Individuals with exudative AMD may complain of visual loss, metamorphopsia, scotoma, micropsia, photopsia, and formed hallucinations (Charles Bonnet syndrome). In cases of unilateral exudative AMD, symptoms include poor depth perception and the need to close the “bad” eye to see fine detail.

Clinical Features

Choroidal neovascularization appears as a grayish green lesion associated with subretinal fluid, subretinal hemorrhage, and/or lipid exudation. In many individuals, the most significant findings are subretinal fluid with or without subretinal hemorrhage. Serous PEDs are round or oval, sharply demarcated dome-shaped elevations of the retinal pigment epithelium (RPE). Additional complications of CNV include RPE tear, massive subretinal hemorrhage (usually in patients receiving anticoagulant therapy), radiating chorioretinal folds, and rarely vitreous hemorrhage. Ultimately, most individuals develop a fibrovascular scar in the macula.

Ancillary Testing

Fluorescein angiography is used to determine the type and location of the CNV. The type of CNV is divided into two categories: classic or occult. Classic CNV is characterized by a lacy vascular network with welldemarcated borders during the early phase of the angiogram followed by late leakage. Occult CNV includes fibrovascular PEDs that appear as poorly defined areas of hyperfluorescence early followed by late leakage, and late leakage of undetermined source. Location is defined in terms of the relationship of the CNV to the center of the fovea: extrafoveal (200 m to 2500 m), juxtafoveal (1 m to 199 m), and subfoveal (under the fovea).

Fluorescein angiography may help to distinguish a nonvascularized, serous PED (commonly seen in central

serous chorioretinopathy) from a fibrovascular PED seen in AMD. Fluorescein angiographic features suggesting a fibrovascular PED include hot spots, notched PEDs, and an irregular filling pattern.

Indocyanine green (ICG) angiography may be considered for lesions associated with subretinal hemorrhage or PED in which the borders of CNV are not clearly defined. Patterns of ICG angiography in AMD include focal hot spots, plaques of hyperfluorescence, and combination lesions.

Pathology/Pathogenesis

Abnormalities in the RPE/Bruch’s membrane complex allow capillaries from the choroidal circulation to gain access to the sub-RPE and subneurosensory retinal space. Neovascular proliferation is associated with the accumulation of subretinal fluid, blood, and exudate— ultimately leading to fibrovascular scarring. The stimulus for angiogenesis remains unknown.

Treatment/Prognosis

The Macular Photocoagulation Study (MPS) demonstrated the effectiveness of laser photocoagulation in reducing the risk of severe visual loss in eyes with CNV that meet the eligibility criteria. Treatment benefit was significant for extrafoveal, juxtafoveal, and subfoveal classic CNV membranes. Persistence and recurrence of CNV (greater than 50%) limit the long-term efficacy

of laser treatment. Photodynamic therapy (PDT) has become the preferred treatment for patients with predominantly classic subfoveal CNV. Photodynamic therapy uses the light-activated dye verteporfin to obtain closure of the CNV without the associated retinal damage of traditional thermal laser. Unfortunately, the effects are temporary, and most patients require 4 to 6 treatments over the course of 2 years. No effective treatment has yet been developed for occult CNV.

Experimental therapies for exudative AMD include submacular surgery, macular translocation, feeder vessel photocoagulation, antiangiogenic drug therapy, and radiation therapy.

Systemic Evaluation

Age-related macular degeneration may be associated with cardiovascular risk factors including hypertension and a history of cigarette smoking. A general physical examination and smoking cessation are strongly recommended.

Exudative age-related macular degeneration is characterized by the presence of subretinal fluid, subretinal hemorrhage, and lipid exudate.

Exudative age-related macular degeneration is caused by the proliferation of new vessels from the choroidal circulation to the subretinal pigment epithelial and/or subneurosensory retinal space. Fluorescein angiogram of “classic” choroidal neovascularization shows a welldefined area of lacy hyperfluorescence in early view.

Occult choroidal neovascularization includes fibrovascular pigment epithelial detachments that appear as poorly defined areas of hyperfluorescence early followed by late leakage, and late leakage of undetermined source. The early phase of the fluorescein angiogram demonstrates blocking of fluorescence due to large subretinal hemorrhage.

Over time, fibrovascular proliferation results in the development of a disciform scar in the macula.

The late-phase angiogram is characterized by prominent hyperfluorescence as a result of leakage.

Superonasal to fovea is a small component of classic choroidal neovascularization (CNV). The late-phase angiogram demonstrates a larger area of poorly defined leakage consistent with a larger occult CNV.

Pigment epithelial detachment is a well-defined, domeshaped elevation of the retinal pigment epithelium. It results from fluid and blood accumulation between the RPE and Bruch’s membrane.

Fluorescein angiogram of the pigment epithelial detachment in the previous figure shows irregular fluorescein filling of the pigment epithelial detachment with an adjacent area of late leakage indicative of occult choroidal neovascularization.

Massive subretinal hemorrhage may be seen in patients with exudative age-related macular degeneration. These patients often have a history of anticoagulation therapy.

The prognosis for visual recovery is poor.

Exudative age-related macular degeneration with chronic choroidal neovascularization leakage may demonstrate a “Coats-like” response with massive lipid exudate surrounding the choroidal neovascularization complex.

A retinal pigment epithelial tear or rip may occur spontaneously or following laser photocoagulation for choroidal neovascularization. Fundus examination reveals a round or oval region of retinal pigment epithelial atrophy adjacent to a region of “clumped up” retinal pigment epithelium.

The fluorescein angiogram of the fundus picture in the previous figure demonstrates hyperand

hypofluorescence corresponding to the retinal pigment epithelial alterations.

Laser photocoagulation may reduce the risk of visual loss related to exudative age-related macular degeneration. This 68-year-old woman presented with choroidal neovascularization in her left eye.

Laser photocoagulation was performed. This fundus photograph taken 6 weeks after laser photocoagulation reveals a well-demarcated area of atrophy in the treated area. The subretinal blood and fluid have resolved.

The fluorescein angiogram of the same patient revealed subfoveal classic choroidal neovascularization

with late leakage.

The fluorescein angiogram demonstrates hypofluorescence corresponding to the treated area.

Photodynamic therapy with verteporfin has become the treatment of choice for subfoveal, classic choroidal neovascularization (CNV). This fluorescein angiogram reveals classic CNV before treatment.

This fluorescein angiogram reveals the early effect of photodynamic therapy. Three weeks following treatment, marked hypofluorescence occurs as a result of closure of the choroidal neovascularization.