be hypofluorescent during the early phase and become hyperfluorescent in the late phase of fluorescein angiography. Several lines of evidence indicate that hyperfluorescent (hydrophilic) drusen predispose rather to the development of choroidal neovascularization, whereas hypofluorescent (hydrophobic) drusen may be associated rather with detachment of the retinal pigment epithelium (PED). In optical coherence tomography, drusen appear as small detachments of the RPE of the underlying Bruch’s membrane. However, as quantification of those “elevations” by OCT is not yet available as standard, prognostic evaluation of drusen visualized by OCT has been of no clinical impact to date. In future, automated quantifications of signs of early AMD by OCT will become more important in clinical and preventive therapeutic trials. Also, a clear clinical distinction of those drusenoid detachments of RPE by OCT and serous forms of pigment epithelium detachments must be made (see Chap. 7) to avoid over-interpreta- tion with regard to prognosis and indication for therapy.

6.3Focal Hypopigmentation and Hyperpigmentation of the Retinal Pigment Epithelium

Pigmentary irregularities are frequently associated with all forms of AMD (Fig. 6.7). Focal hyperpigmentation may result from changes at the level of the RPE, i.e., increased melanin content and/or proliferation of pigmented epithelial cells or from migration of pigment-containing cells (cells of the RPE or macrophages that have phagocytosed melanin) into the neurosensoric retina. This phenomenon can also be observed in intraretinal neovascular complexes (retinal angiomatous proliferations, RAP lesions) or retinochoroidal vascular anastomoses. Various investigations have demonstrated that presence of focal hyperpigmentation is a strong risk factor for the development of choroidal neovascularizations. Focal areas of hypopigmentation can occur independently of drusen, either through focal loss of retinal pigment epithelial cells or due to reduced content of intracellular melanin granules. If there are no additional changes, the retinal sensitivity corresponding to those areas usually shows no measurably impairment.

Fig. 6.7 Focal hyperpigmentations as an additional high-risk characteristic in the presence of multiple drusen

6.4Abnormal Choroidal Perfusion

In some patients with AMD, an abnormal choroidal perfusion is seen on fluorescein angiography. A delayed fluorescein angiographic filling of the choroid has been defined as an area at least five disc diameters across, with a region of slowly developing point-shaped or spotted choroidal fluorescence in the transit phase. These hyperfluorescent regions do not coalesce until the venous phase of the retinal circulation. In addition, large choroidal vessels are visible in the transit phase before the filling of the choriocapillaris (Fig. 6.8). Similar angiographic findings are recorded in Sorsby’s fundus dystrophy, an autosomal dominantly inherited macular dystrophy with diffuse deposits in the inner Bruch’s membrane. By extension to AMD, the presence of choroidal filling delays is thought to indicate the presence of diffuse drusen [31, 32]. As outlined in Chap. 5, such diffuse deposits between the RPE and Bruch’s membrane may play a crucial part in the pathogenesis of AMD. Therefore, it is not surprising that patients with the angiographic sign of delayed choroidal perfusion have a rather unfavorable prognosis compared with patients in whom this sign is absent. Interestingly, when this sign is present, early-stage disease with soft drusen progresses to geographic atrophy rather than to neovascular AMD [5].

Summary for the Clinician

›Clinical signs of early AMD are drusen and focal hypoor hyperpigmentations of the RPE. They develop on a genetic basis and initially lead to only minor visual impairment. In clinical classification, consistency in terminology and precise differentiation of findings are required due to their potential for prognostic relevance and as a guide to the requirement of prophylactic or therapeutic interventions. Drusen dynamically change over time and usually show a symmetrical occurrence for each patient such as with other manifestations of AMD. The presence of drusen is associated with an increased risk of choroidal neovascularizations, retinal pigment epithelial detachments, and geographic atrophy. Notably, large, soft, and confluent drusen with additional focal hyperpigmentation are associated with a particularly high risk of AMD progression.

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Core Messages

›There are characteristic presenting symptoms and signs suggestive of choroidal neovascularization.

›The most common presenting symptom is decreased visual acuity. Distortion is probably the second most common complaint.

›Decreased reading ability is what patients notice first. Amsler grid testing has proven to be suboptimal for at home testing.

›Patients may present with hemorrhage, cystoid macular edema, subretinal fluid, and pigment epithelial detachment.

›Testing modalities such as fluorescein and indocyanine green angiography, autofluorescence imaging, and optical coherence tomography are employed to help make the diagnosis and to quantify disease severity.

7.1Introduction

Choroidal neovascularization (CNV) presents with a variety of visual symptoms and signs that can serve as clues to the proper diagnosis [1–3]. The physical invasion of blood vessels and associated cellular infiltrate distorts retinal tissue. Associated leakage, bleeding, and eventual scarring can have profound effects on macular function. Recognition of the presence of CNV is fairly

R.F. Spaide

Vitreous-Retina-Macula Consultants of New York,

Manhattan Eye, Ear, and Throat Hospital, New York, NY, USA e-mail: rickspaide@yahoo.com

easy in advanced cases, but by then, there often is severe vision loss. CNV secondary to age-related macular degeneration (AMD) used to be the leading cause of legal blindness among older adults [4]. With modern treatments aimed against vascular endothelial growth factor (VEGF), the visual acuity in a large majority of patients can be stabilized over the long term, but visual acuity improvement occurs in a minority of patients [5, 6]. Therefore, early diagnosis, prior to the patient suffering severe loss of vision, is the best hope of maintaining visual function in these older adults.

7.2Symptoms Secondary

to Choroidal Neovascularization

7.2.1Decreased Visual Acuity

The principal symptoms are loss of vision, distortion, and visual field defects. Patients often have the presenting complaint that they cannot see from one eye and on closer questioning reveal that they actually mean they have decreased central vision in the eye. The mean visual acuity of patients entering recent randomized studies has been approximately 20/80 [5–7]. These patients are selected because of the lack of other eye diseases and relatively simple presentations of CNV; for example, patients with massive hemorrhage are not generally enrolled in clinical trials. On rare occasion, massive hemorrhage, particularly in anticoagulated patients, may cause profound loss of vision including no light perception [8].

Patients will notice the loss of acuity when tasks that were formerly easy become more difficult or frankly impossible. If the dominant eye is primarily affected, the