Miscellaneous Rare Macular Dystrophies


Fig. 10.1
Clinical stages of central areolar choroidal dystrophy (CACD). (a) Fundoscopy of stage 1 CACD reveals slight parafoveal hypopigmentation. (b) This area of hypopigmentation on ophthalmoscopy corresponds with an area increased fundus autofluorescence (FAF). (c) Fluorescein angiography (FA) in stage 1 CACD shows hyperfluorescent parafoveal changes. (d) In stage 2 CACD, a round to oval area of hypopigmentation is visible in the macula. (e) This area corresponds to speckled changes of increased and decreased FAF. With time, initially increased FAF evolves to decreased FAF changes as the lesion enlarges and atrophy of the retinal pigment epithelium (RPE) progresses. (f) FA in stage 2 CACD shows speckled hyperfluorescence of the lesion, due to partial RPE atrophy. (g) Stage 3 CACD shows one or more patches of well-circumscribed chorioretinal atrophy, appearing outside the central fovea, within the area of slight hypopigmentation. (h) These areas of chorioretinal atrophy correspond to severely decreased to absent FAF. (i) In stage 4 CACD, the well-defined area of chorioretinal atrophy involves the fovea, with a corresponding severe decrease in visual acuity. (j) This area corresponds with a round to oval zone of absent FAF involving the fovea in late stage 4 CACD, bordered by a small residual band of increased FAF. (k) End-stage CACD also shows a well-demarcated area of chorioretinal atrophy on the fluorescein angiogram, with enhanced visibility of the residual underlying choroidal vessels. (l) Patient with early stage 3 CACD, showing a small, round, black area of profound RPE atrophy (thus making it stage 3 CACD) in addition to the speckled FAF changes. (m) Spectral-domain optical coherence tomography image (SD-OCT) through the deeply atrophic area shows more marked atrophy of the outer retina (external limiting membrane and ellipsoid) and RPE, surrounded by more discrete outer retinal changes. (n) SD-OCT section taken through the fovea, showing mainly an attenuated outer retina with a hyperreflective ellipsoid line that is absent in the central macula, but with a relatively preserved external limiting membrane

Fluorescein angiography shows progressive hyperfluorescence due to window defects as a result of progressive RPE atrophy in advancing CACD stages (Fig. 10.1c, f i, k,; Table 10.1).

Table 10.1
Summary of clinical characteristics of central areolar choroidal dystrophy (CACD)

CACD stage

Mean visual acuity (range)


Optical coherence tomography (OCT)

Fundus autofluorescence (FAF)

Fluorescein angiography


Stage 1

20/20 (20/33 – 20/20)

Slight parafoveal pigment changes

Mild irregular reflectivity changes of outer photoreceptor – retinal pigment epithelium (RPE) complex

Increased parafoveal FAF

Mild parafoveal hyperfluorescence


Stage 2

20/23 (20/80 – 20/16)

Round to oval mildly atrophic hypopigmented area

Irregular reflectivity changes of outer photoreceptor – RPE complex

Speckled increased and decreased FAF

Speckled hyperfluorescence (mild RPE window defect)


Stage 3

20/27 (20/100 – 20/16)

Appearance of profound chorioretinal atrophy outside fovea

Marked thinning of outer photoreceptor structures in atrophic zone; relative sparing of fovea

Well-defined atrophic area of absent FAF outside fovea

Visible remaining hyperfluorescent choroidal vessels in atrophic area

Normal or cone/cone-rod dysfunction

Stage 4

20/182 (20/400 – 20/33)

Profound chorioretinal (geographic) atrophy affecting fovea

Marked thinning of outer photoreceptor structures in atrophic zone including fovea

Well-defined atrophic area of absent FAF affecting fovea

Like stage 3

Normal or cone/cone-rod dysfunction

Fundus autofluorescence in early CACD shows speckled changes of increased and decreased FAF, whereas in stage 3 and 4 CACD, a black “punched-out” lesion due to profound RPE atrophy is seen in the posterior pole, bordered by a small residual band of increased autofluorescence (Figs. 10.1b, e, h, k) [4]. On optical coherence tomography (OCT), mildly atrophic lesions in stage 1, 2, and 3 central areolar choroidal dystrophy correspond to variable alterations in the reflectivity of the outer retina, generally without drusen (Figs. 10.1l, m). In the profoundly atrophic areas in stage 3 and 4, the outer retinal layers are markedly attenuated (Fig. 10.1m, n).

The photopic and scotopic full-field electroretinography (ERG) is generally normal in CACD, but panretinal cone or cone-rod dysfunction can develop in advanced CACD [1]. The pattern ERG is usually reduced or extinguished, and the multifocal ERG often shows markedly decreased (para-)central responses [3, 4]. The electro-oculography (EOG) is normal.

10.2.3 Disease Course

As in all PRPH2-associated retinal dystrophies, the disease severity in patients with an identical PRPH2 mutation may be highly variable, even in mutation carriers from the same family [1]. Non-penetrance has been observed in up to 21 % of patients [4]. Therefore, cases can appear sporadic or automal recessive. The visual prognosis of PRPH2-related CACD roughly depends on the underlying mutation [1]. Visual acuity can be relatively preserved for many years, as it can take more than 20 years for CACD to progress from stage 2 to stage 4. Choroidal neovascularization is very rare and can be seen in patients with concurrent high myopia. Retinal atrophic changes in CACD can predispose to effects of vitreomacular traction and macular hole formation.

10.2.4 Differential Diagnosis

Early CACD should be differentiated from atrophic age-related macular degeneration, mitochondrial retinal dystrophy caused by the m.3243A>G mutation (for instance, in association with maternally inherited diabetes and deafness; see Chap. 8), North Carolina macular dystrophy, malattia leventinese/Doyne honeycomb retinal dystrophy, Sorsby fundus dystrophy, Stargardt disease, and cone(-rod) dystrophy [5]. Stage 3 and 4 CACD can be similar to all macular diseases with advanced chorioretinal atrophy.

10.2.5 Conclusion

CACD is an autosomal-dominantly inherited macular dystrophy with a relatively late onset, caused by mutations in the PRPH2 gene.

10.3 Dominant Cystoid Macular Dystrophy

10.3.1 Background

Dominant cystoid macular dystrophy was first described by Deutman and colleagues in 1976 [6, 7]. This peculiar autosomal-dominant dystrophy is characterized by early-onset macular cystoid fluid collections (possibly edema). The gene locus is linked to the interval 7p15.3, but the exact gene and pathogenesis are currently unknown [8, 9].

10.3.2 Clinical Findings

Patients start to experience a slowly progressive loss of visual acuity in childhood. Most patients are moderately to highly hyperopic. DCMD can be classified into three stages, based on characteristics on ophthalmoscopy, fundus autofluorescence, fluorescein angiography, OCT, as well as electrophysiological characteristics (Table 10.2, Fig. 10.2) [9]. The staging system correlates with age and visual acuity. In stage 1, DCMD patients are younger than 20 years and have cystoid fluid collections (CFCs) in the macula with fine folding of the internal limiting membrane and mild pigment changes (Fig. 10.2a–e). In stage 2 DCMD, the CFCs decrease in size, and moderate macular chorioretinal atrophy develops. Patients with stage 3 DCMD are older than 50 years and show profound chorioretinal atrophy and coarse hyperpigmented deposits in the posterior pole.

Table 10.2
Summary of clinical characteristics of dominant cystoid macular dystrophy (DCMD)

Disease stage

Mean age [range]

Mean VA [range]


Optical coherence tomography (OCT)

Fundus autofluorescence (FAF)

Fluorescein angiography



Goldmann visual field

Stage 1

13 [0–32]

20/37 [20/15 – 20/200]

Fine folding of inner limiting membrane

Cystoid fluid collections (CFCs)

Mild granular pigment changes in macula


Mildly increased FAF in the macula

Hyperfluorescent CFCs

Perifoveal capillary dilation


Mildly reduced



Stage 2

38 [21–50]

20/54 [20/20 – CF]

Mild but visible chorioretinal macular atrophy


Mild retinal atrophy

Small CFCs

Moderately decreased FAF in macula

Hyperfluorescent CFCs

Normal to mildly – severely reduced (68 %)

Normal, minority (<20 %) subnormal cone and rod function

Peripheral visual field constriction in 25 % of patients

Stage 3

61 [44–90]

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May 26, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Miscellaneous Rare Macular Dystrophies
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