are almost always present in both eyes although frequently are asymmetric. Late manifestations of non-neovascular AMD are geographic and nongeographic atrophy of the RPE. Geographic atrophy is a well-demarcated area of retinal thinning that allows for increased visualization of the underlying choroidal vessels. They may be located centrally in the macula, peripapillary, or both.

Ancillary testing of patients with dry AMD may include color fundus photography to aid in the description of drusen and for documenting progression or change. Optical coherence tomography (OCT) and FA may be helpful in ruling out neovascular component or highlighting areas of atrophy. Fundus autofluorescence can delineate areas of atrophy and help in cases when the diagnosis is in question. Patients should be advised to perform monocular amsler grid testing to detect early neovascular changes. Each box represents one degree of visual field, and the grid is testing the central 10° of fixation. Leakage of blood or serum such as in subretinal hemorrhage, subretinal fluid, hard exudates, and macular edema all herald the onset of neovascular AMD. Although hemorrhage has been described in geographic atrophy without CNV, hemorrhage almost always represents neovascular AMD [41].

Clinically, exudative AMD has a multitude of clinical appearances. The hallmark feature of wet AMD is the choroidal neovascularization (CNV). This classically appears as a grayish-green membrane beneath the retina in a macula that has accompanying drusen. Using stereo-ophthalmoscopy, one can appreciate findings such as separation of the retina from underlying RPE (subretinal fluid), subRPE fluid (PED), and intraretinal changes (cystoid macular edema). The ophthalmoscopic appearance of CNV, however, is often more subtle. RPE detachments can represent an underlying neovascular complex and appear as a near translucent and welldemarcated subretinal lesion. At times, the only clinical finding of CNV may be subretinal lipid. Other clinical findings found in neovascular AMD include subretinal hemorrhage, vitreous hemorrhage, hemorrhagic RPE detachments, and in the late stages subretinal fibrosis with disciform scars of the macula. Ancillary testing that can assist in the diagnosis of neovascular AMD include OCT to detect subtle sub-RPE and subretinal and retinal

material (fluid, hemorrhage, exudates, fibrosis). FA is particularly useful in diagnosing leakage from a CNV or pooling of an RPE detachment. It is also useful in delineating lesion location, size, and for determining disease activity, progression, and response to treatment. For diagnostic purposes, ICG is useful in atypical cases of neovascular AMD, in cases of idiopathic polypoidal choroidal vasculopathy, retinal angiomatous proliferation, or when the diagnosis is in question.

Pearl

Consider indocyanine green angiography (ICGA) in cases when the diagnosis of typical exudative AMD is in question or in cases that are poorly responsive to antiVEGF therapy.

Differential Diagnosis

Because both dry and wet AMD can present in various ways, the differential diagnosis for each entity is fairly large. Subtle features in the history, presentation, personal attributes, family history, fundus appearance, and findings on ancillary testing are essential to differentiate each of the entities. Differentiating these conditions is vitally important as the treatment options and prognosis may vary considerably.

Nonexudative AMD

Central Serous Chorioretinopathy (CSCR)

The classic presentation includes serous retinal detachments, though many patients have focal RPE irregularities thought to be evidence of old episodes. The RPE hypopigmentation can be mistaken for dry AMD. Key differentiating features include younger age in CSCR, 25–50, and the presence of serous retinal detachment in the absence of drusen. OCT is particularly useful in these cases. CSCR in individuals above 50 years of age do have a higher prevalence in females (Fig. 3.10) [42–46].

Fig. 3.10 (a) OCT and (b) fluorescein angiogram of a patient with central serous chorioretinopathy with a serous detachment of the fovea on OCT and multiple pinpoint areas of hyperflourescence on fluorescein angiogram

Fig. 3.11 Myopic degeneration in a middle aged woman with spectacle correction of −11.50 diopters

High Myopia

Patients with high myopia can develop retinal and RPE atrophy. The key differentiating features of this condition is the history of significant myopia (at least 6 diopters). Other features include lack of drusen, presence of lacquer cracks (yellow subretinal streaks), macular hyperpigmented spots (Fuchs spot), and optic nerve anomalies including an oblique insertion (tilted) of the optic nerve and an area of white sclera and/or choroidal vessels (myopic crescent) surrounding the optic nerve (Fig. 3.11) [47, 48].

Stargardt’s Disease/Fundus Flavimaculatus

Many patients with Stargardt’s disease have normal appearing fundi, though patients may have yellow fleck-like deposits at the level of the RPE

and atrophic macular changes as in dry AMD. Key differentiating features include: age of vision loss in Stargardt’s disease usually occurs in the first several decades and the typical FA findings. Patients with Stargardt’s disease often have a “dark choroid” pattern on FA, in which the retinal circulation is highlighted against a hypoflourescent choroid. Bull’s eye maculopathy can occur in both Stargardt’s disease and dry AMD with GA (Fig. 3.12) [49, 50].

Cuticular Drusen

These drusen are small and numerous and usually initially seen in patients aged 30 to 40, though the patients may not present until they are older. On FA, there is a classic “starry night” pattern, which highlights even more drusen than can be seen on ophthalmoscopy [3].