Book · Chapter 3 Published online on 10 October 2026

Definition

Age-related maculopathy (ARM), sometimes called early AMD, comprises all the age-related changes of the fundus that may precede neovascular or atrophic AMD (also known as late AMD). These signs generally appear around the age of fifty.

ARM is characterised by alterations of the retinal pigment epithelium (RPE): depigmentation of the pigment epithelium or hyperpigmentation (pigment migration or clumps). It also presents as subretinal deposits (or drusen), which include miliary drusen, isolated or confluent serous drusen, reticular pseudodrusen, cuticular drusen, refractile drusen and ghost drusen. The prevalence of these lesions in the general population varies considerably with age (25% after 52 years to 87% after 80 years).

Although they do not systematically progress to AMD, their presence constitutes a risk that warrants careful assessment and close monitoring. A predictive score for exudative AMD has been proposed on the basis of fundus analysis. This score ranges from 0 to 2 for each eye depending on the absence or presence of drusen larger than 125 microns or RPE alterations, giving an individual a score of 0 to 4. The 5- and 10-year neovascular risk was then evaluated in the AREDS study (Tables 1 and 2). Nowadays, two entities are distinguished within ARM: early AMD and intermediate AMD. Early AMD is characterised by the presence of numerous small drusen (< 63 microns, “miliary” drusen, or hard drusen in the English-speaking literature) or drusen of intermediate size (≥ 63 microns but < 125 microns, “serous” drusen, or soft drusen in the English-speaking literature). Intermediate AMD is defined by the presence of extensive small or medium-sized drusen, or by large drusen (≥ 125 microns). Small drusen are frequently observed in people aged 50 and over, and may represent an epiphenomenon of ageing. Consequently, intermediate drusen are more specific and are more likely to be a marker of age-related macular degeneration than of normal ageing.

Pigment migration No = 0 Yes = 1

Table 1: Score proposed in AREDS report no. 18. A score is assigned to each eye according to the presence or absence of pigment migration and of drusen larger than 125 microns in diameter. If one eye is more severely affected, its score is automatically 2 points, the other being assessed according to the scale above. For intermediate drusen (63 µm to 125 µm), the score is 0.5, i.e. a score of 1 if both eyes are affected.

0 0% 0,5% 1 3% 8%

2 12% 22% 3 25% 49% 4 50% 66%

Table 2: 5-year and 10-year risk of AMD according to the AREDS score. Risk scale for progression to a severe form (neovascular or atrophic, in one or both eyes) of the patients included in AREDS.

Classification of ARM

Alterations of the retinal pigment epithelium

RPE alterations are considered markers of early AMD and are defined as hyperpigmentation and/or hypopigmentation present in the macular area, within two disc diameters of the fovea, with or without drusen and with no other known retinal disease. Many studies show that these RPE alterations carry a high risk of progressing to severe AMD, warranting close and regular monitoring so that complications can be detected as early as possible (Figure 1).

Colour photograph (A): pigment migration visible as a clumped pigmented lesion in the central region, associated with serous drusen. SD-OCT with infrared image in vertical B-scan section (B, C) showing a localised hyperreflective RPE with posterior shadowing corresponding to the hyperpigmentation (red arrow). The section also crosses dome-shaped elevations of the pigment epithelium corresponding to serous drusen.

Miliary drusen

Miliary drusen are reported to be present in 25 to 50% of people over 50. On fundus examination, they are round, small (diameter < 63 µm), with sharp edges, yellowish, often numerous and located temporal to the fovea.

On fluorescein angiography, they appear hyperfluorescent from the early phases of the angiogram, through a window effect. On SD-OCT, they cause very minimal elevations of the RPE (Figure 2). They may become confluent and progress to larger drusen and be associated with serous drusen or reticular pseudodrusen. Progressive complications are relatively rare and late; when miliary drusen are isolated, they are usually stable.

Colour photograph (A) showing round, regular, small (< 63 µm), yellowish miliary drusen (white arrow). On fluorescein angiography (B), the miliary drusen appear hyperfluorescent from the start of the sequence and are better visualised than on the colour photograph (white arrow). SD-OCT (C): minimal elevations of the RPE corresponding to the miliary drusen (white circle).

Serous drusen

Serous drusen are larger (diameter > 63 µm), with blurred outlines and an irregular shape, paler than miliary drusen and often associated with pigment migration.

On fluorescein angiography, they are hypofluorescent in the early phase, then stain and become hyperfluorescent. They always remain hypofluorescent on ICG. OCT shows multiple moderately reflective dome-shaped elevations of the RPE, in the form of a bulge or hump. Visibility of the external limiting membrane and of the ellipsoid line is often preserved (Figure 3A).

Serous drusen may become confluent and form a true pigment epithelial detachment (PED), known as “drusenoid”, with hyperreflective content. Drusenoid PEDs may progress, after a few years, to true areas of atrophy as the PED gradually collapses (Figure 3B).

Serous drusen lead to late AMD in the long term in about 30% of cases. In rare cases, serous drusen may regress or sometimes even calcify, giving ghost drusen associated with an underlying atrophic process.

Colour photograph (A) showing multiple lesions with blurred outlines, paler than the very numerous miliary drusen, measuring here more than 125 µm and located in the macula, corresponding to serous drusen (white circle). Fluorescein angiography (B), intermediate phase showing progressive, delayed staining of the serous drusen (white circle), without leakage. ICG in the late phase (C): the serous drusen remain hypofluorescent (white circle). SD-OCT section through the serous drusen (D): multiple dome-shaped elevations of the RPE (white arrow) with homogeneous hyperreflective content and preserved visibility of the external limiting membrane and the ellipsoid zone in this case, without associated exudation.

Reticular pseudodrusen

Reticular pseudodrusen, or blue drusen, were first described by the Créteil team. They are yellowish drusen located preferentially along the superior temporal arcades; they are also found in the macula and the peripheral retina, and have a so-called “cerebroid” appearance (Figure 4).

They were named blue drusen because of their good visibility on blue-light photographs. On SD-OCT, they are hyperreflective. They may alter the ellipsoid zone and are associated with a thinned choroid on EDI-OCT.

These deposits are located above the RPE, unlike serous drusen, which are beneath the RPE. On fluorescein angiography they are poorly visible or hypofluorescent. In the late phase of ICG they appear as a hypofluorescent network.

Four stages of progression have been described on SD-OCT. In the early stage (stages 1 and 2), the hyperreflective material located above the RPE thickens over time, and in the advanced stages (stages 3 and 4), the material fragments and there is discontinuity, or even absence, of the ellipsoid line. Several studies have shown a high risk of progression to atrophic or exudative AMD, and more particularly to type 3 neovascularisation.

Colour photograph (A): lesion of about one disc diameter forming a drusenoid PED (red arrow) through confluence of drusen with pigment migration (white arrow). Fluorescein angiography in the intermediate phase (B) showing a masking effect due to the pigment migration (white arrow), contrasting with the progressive hyperfluorescence of the drusenoid PED (red arrow). Infrared image and corresponding SD-OCT section (C, D) showing a marked undulating elevation of the RPE forming a drusenoid PED (red arrow) with pigment migration (white arrow). Two years later (E), the drusenoid PED has collapsed with progression to atrophy (blue arrow) marked by posterior hyperreflectivity.

The colour photograph (A) shows yellowish pseudodrusen with a cerebroid appearance located along the superior temporal arcades (white star). The pseudodrusen are better seen on the blue-light photograph (B) (white star). On ICG (C), the pseudodrusen are hypofluorescent in the late phase (white star). SD-OCT (D): hyperreflective pseudodrusen (white star), dense in front of the RPE, irregular with a spindle-shaped appearance and able to alter the ellipsoid zone and the photoreceptors. Blue drusen are associated with a thinned choroid on EDI-OCT.

The colour photograph (A) shows yellowish pseudodrusen with a cerebroid appearance, predominantly in the temporal region of the macula (blue arrow), associated with larger rounded yellowish deposits corresponding to serous drusen (red arrow). The pseudodrusen are better seen on the blue-light photograph (B) (blue arrow). On fluorescein angiography in the intermediate phase (C), the serous drusen are hyperfluorescent while the blue drusen are hypofluorescent (red arrow). On SD-OCT (D), the pseudodrusen are hyperreflective, dense in front of the RPE and irregular (blue arrow) with a spindle-shaped appearance, compared with serous drusen, which appear as dome-shaped elevations of the RPE with homogeneous hyperreflective content beneath the RPE (red arrow).

Cuticular drusen

Cuticular drusen were first described in 1977 by D. Gass (Figure 6). They are round (25-75 microns) and numerous subretinal deposits, concentrated mainly at the posterior pole and sometimes in the peripheral retina. They occur in younger subjects than in AMD, with a mean age of 57 years. There is a risk of progression to late stages of AMD after the age of 70.

The angiographic appearance is characteristic: “Milky Way” or “stars in the sky”. Cuticular drusen are located between the RPE and Bruch's membrane. On OCT, their appearance is very specific, sawtooth-shaped, with a shallow elevation or a mound shape. The choroid shows a typical “barcode” reflectivity, with alternating hyperreflective and hyporeflective regions facing the drusen.

They may progress to the appearance of vitelliform material, choroidal neovessels (most often type 1) or atrophy.

Although their ultrastructural characteristics are similar to those of miliary drusen, their life cycle and macular complications are more comparable to those of serous drusen.

Colour photograph (A): numerous round yellowish subretinal deposits (25-75 microns), concentrated on the macula, corresponding to cuticular drusen (blue arrow). Fluorescein angiography (B) shows a characteristic Milky Way or “stars in the sky” appearance, with more lesions than on the colour photograph (blue arrow). SD-OCT (C): sawtooth appearance with a shallow elevation or a mound shape (blue arrow), producing a “barcode” appearance on the choroid (red bracket), with alternating hyperreflective and hyporeflective regions facing the drusen.

“Calcified”, “regressive” or “refractile” drusen

Calcified drusen were initially described by Gass in 1973; they are also called refractile because of their appearance on fundus examination. More recently, the term calcified drusen has given way to the term regressive drusen.

Indeed, drusen are deposits of extracellular material rich in lipids (cholesterol) between the basement membrane of the RPE and the inner layer of Bruch's membrane. Certain phagocytosis processes have been observed, with a reduction in drusen size. Regressive drusen, or “regressing drusen”, consist of deposits of calcified lipid material (cholesterol) not phagocytosed by macrophages, and are characterised by the presence of an intensely hyperreflective band on SD-OCT at the choroidal level (Figure 7).

Multicolor® image showing a calcified drusen (white arrow) with a refractile appearance, with an OCT B-scan section through the lesion. The SD-OCT here shows the presence of an intensely hyperreflective band corresponding to lipid material (cholesterol) that has not been phagocytosed (white arrow).

Ghost drusen

Ghost drusen, first described by the Créteil team, appear on OCT as pyramid-shaped hyperreflective structures, dense in front of the RPE, and are associated with atrophic AMD. They are poorly visible on fluorescein angiography and appear iso- or hyperfluorescent against a background of atrophy (Figure 8). In a recent study analysing the origin of ghost drusen, the authors found, in a small number of cases, the initial presence

of serous drusen.

Multicolor® image (A): ghost drusen predominating facing the areas of atrophy (white arrow). Infrared image (B): hyporeflective lesion surrounded by a hyperreflective zone, with a few small white dots corresponding to the location of the ghost drusen (white arrow). Autofluorescence image (C): the ghost drusen (white arrow) appears as a relatively hyperautofluorescent lesion compared with the adjacent superior atrophy. SD-OCT (D): hyperreflective pyramidal structure characterised by a hyporeflective centre (white arrow).

Age-related maculopathy and

OCT angiography

OCT angiography (OCT-A) is a non-invasive imaging technique that allows selective visualisation of the retinal and choroidal circulation. Serous drusen cause, in most cases, signal attenuation within the choriocapillaris, and segmentation errors may occur depending on the morphology of the drusen (Figure 9). In the case of reticular pseudodrusen, Alten et al. recently described, at the level of the choriocapillaris, a marked decrease in vascular density and in the decorrelation signal index, suggesting functional involvement of the choriocapillaris with areas of non-perfusion that are statistically larger than in the absence of pseudodrusen.

OCT-A allows a new semiological analysis of ARM, sometimes allowing us to detect earlier a risk of progression to a late form. “Vascularised drusen” are an entity described by Querques et al.24 whose main hypothesis is the presence of a type 1 neovascularisation that mimics serous drusen (Figure 9). A recent study from the Tufts team found this type of drusen in 9.4% of eyes with intermediate AMD, raising questions about the follow-up schedule for these patients and their therapeutic management. Despite the masking effect on the choriocapillaris generated by drusen and potential artefacts, OCT-A can provide useful information on choriocapillaris non-perfusion and possible neovascularisation of these lesions.

ICG angiography, early phase (A) and late phase (B). From the early phase, a hyperfluorescent lesion is noted (green arrowhead), corresponding to a plaque in the late phase. Several serous drusen, corresponding to early and late hypofluorescence, can be seen (white arrow). SD-OCT (C) shows drusenoid detachments corresponding to the two lesions observed. OCT-A (D) shows, in the outer retina segmentation, a discreet hypersignal lesion (green arrowhead). In the choriocapillaris segmentation with projection artefacts (E) and without projection artefacts (F), the hypersignal lesion is visible and corresponds to a vascularised drusen. In contrast, the choriocapillaris signal is attenuated at the level of the serous drusen (white arrow).

Conclusion

Screening for ARM is an essential part of the ophthalmological examination from the age of 55, by means of a fundus examination or retinal photography.

Several types of drusen are described, with a risk of progression to severe AMD. The risk of a neovascular complication is very low for miliary drusen. However, serous drusen more frequently progress to choroidal neovascularisation.

OCT is an essential test to confirm the diagnosis of ARM and to rule out neovascular activity. When progression to an exudative form of AMD is suspected, the role of angiography is receding and OCT-A provides useful information on possible neovascularisation.

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Content written and reviewed by Dr Mayer Srour, ophthalmic surgeon in Noisy-le-Grand (Grand Paris Ophtalmologie). Chapter authors: Mayer Srour. Chapter taken from DMLA : panorama des formes cliniques (AMD: overview of clinical forms), O. Semoun, M. Srour, É. Souied and the ophthalmology team of CHI de Créteil, Théa Pharma, 2019. Reproduced with the publisher's permission. Full book in PDF. This article is for information only and does not replace a consultation. Last updated: 10 October 2026.