West African Crystalline Maculopathy (WACM) is a rare idiopathic maculopathy observed in people of West African origin. It is characterized by the deposition of birefringent yellow-green crystals near the fovea, is usually asymptomatic, and can be bilateral or unilateral.
In 2003, David Sarraf et al. first reported it in six unrelated middle-aged to older adults (54–69 years) of the Igbo tribe in southeastern Nigeria. 1) To date, fewer than 30 cases have been reported in the literature. 1)
Onset is typically observed between the ages of 40 and 70. The youngest reported case in the literature is a 39-year-old Nigerian woman. 1)
The ethnic groups and regions reported to be affected are as follows:
Almost all reported cases to date belong to ethnic groups from West Africa (or of West African descent). Geographic and ethnic clustering is prominent, suggesting a genetic predisposition or an association with environmental factors common in West Africa. 1) WACM has not been sufficiently reported in individuals from outside West Africa.
WACM is usually asymptomatic. The crystal deposits themselves are not known to cause vision loss, and are often discovered incidentally during ophthalmic examinations for other diseases.
If there is a concomitant retinal vascular disease affecting the macula (such as diabetic retinopathy or retinal vein occlusion), vision loss due to that condition may be observed. Color vision tests and Humphrey visual field tests are usually normal.
On fundus biomicroscopy, clusters of birefringent yellow-green crystals are observed in the foveal region of the inner retinal layers.
Characteristics of the Crystals
Color and morphology: Clusters of birefringent yellow-green crystals
Location: Inner retinal layer near the fovea (parafoveal)
Distribution: Limited to the foveal avascular zone. Not seen outside the temporal vascular arcades
Other: No parafoveal ring-shaped deposits. No predilection for arteriolar surroundings
Imaging findings
Color fundus photography: Visible as yellow-green crystals near the fovea
Multicolor confocal SLO: Depicts crystals more clearly than color fundus photography1)
OCT: Seen as hyperreflective foci in the inner retina in both eyes1)
Autofluorescence and FFA: Usually show no abnormalities1)
The presence of crystals is bilateral in most cases, but unilateral or markedly asymmetric cases have also been reported.1) Using a rotating polarizing filter can confirm that the crystals are birefringent.
WACM crystals appear as yellowish-green clusters near the fovea and are not seen outside the temporal vascular arcades. They also do not show parafoveal ring-shaped deposits or a predilection for periarteriolar regions, which helps differentiate them from other crystalline maculopathies. However, other causes must be excluded for a definitive diagnosis.
The pathophysiology and composition of WACM crystals remain unknown.1) The following factors have been proposed as hypotheses.
Suspected Associated Factors
Factors that may be involved in the pathogenesis of the disease
The diagnosis of WACM is a diagnosis of exclusion based on the clinical appearance of crystal deposits near the fovea in patients from West Africa. 1)
The following information should be systematically collected:
Systematic exclusion of differential diagnoses for crystalline maculopathy is essential.
| Category | Disease |
|---|---|
| Systemic diseases | Oxalosis, cystinosis, hyperornithinemia, Sjögren-Larsson syndrome, Kjellin syndrome |
| Drug-induced | Talc, tamoxifen, canthaxanthin, nitrofurantoin, methoxyflurane |
| Local ocular diseases | Idiopathic parafoveal telangiectasia, Bietti crystalline dystrophy, calcified macular drusen, chronic retinal detachment |
Bietti crystalline dystrophy is an autosomal recessive disorder caused by abnormalities in the CYP4V2 gene and is common in East Asia (Japan and China). Its course differs significantly from WACM in that it presents with progressive visual field and visual acuity loss. Regarding drug-induced crystal deposition, tamoxifen (phospholipid metabolism disorder), canthaxanthin (a food additive used as a coloring agent), methoxyflurane (an inhalational anesthetic), talc (a tablet excipient), and nitrofurantoin (a urinary tract infection drug) are known to cause crystal deposition in the retina.
At present, no specific biochemical or genetic test for WACM has been established. 1) The diagnosis is made by identifying characteristic fundus findings (yellow-green crystals near the fovea) in patients of West African origin and excluding all other causes of crystalline maculopathy, such as drug-induced, systemic, and local ocular diseases.
There is no specific treatment for WACM. Since WACM itself is asymptomatic and does not threaten vision, the basic approach is observation.
If there are coexisting retinal vascular diseases (such as diabetic retinopathy or retinal vein occlusion), it is important to provide appropriate treatment for each condition.
The pathophysiology of WACM is not yet fully understood. The main hypotheses currently proposed are described below.
Breakdown of the blood-retinal barrier
The most plausible hypothesis is that disruption of the blood-retinal barrier facilitates the entry of endogenous or environmental substances into the retina. The frequent coexistence of vascular diseases such as diabetic retinopathy in many cases supports this hypothesis. 1) Unilateral or asymmetric onset may be explained by an association with unilateral uveitis or retinal vascular disease.
Involvement of Müller cells
A hypothesized pathophysiology is that dysfunction of Müller cells leads to disruption of the inner blood-retinal barrier. This may disturb retinal homeostasis and allow accumulation of crystalline material.
Composition and formation of crystals
The chemical composition of the crystals is unknown, but an association with xanthophylls (macular pigment) has been suggested. 1) Crystals may form over several months. Studies differ on the location of crystals, with reports of involvement in the inner retinal layers, internal limiting membrane, Henle’s layer, outer plexiform layer, and nuclear layers.
Genetic and metabolic factors
Geographic clustering in specific ethnic groups or tribes from West Africa suggests a genetic predisposition or common environmental factors in these populations. 1) However, most cases are unrelated individuals, and few familial cases have been reported, making a simple hereditary disease unlikely.
WACM is an extremely rare disease, and at present there are no published reports on long-term visual complications. 1) Elucidation of the etiology and crystal composition, as well as follow-up studies on long-term prognosis, are future challenges.
Umunakwe et al. (2022) reported the first application of multicolor confocal scanning laser ophthalmoscopy (SLO) and short-wavelength autofluorescence imaging in a case of WACM in a 71-year-old Igbo man. 1) SLO images depicted crystals more clearly than color fundus photography, and autofluorescence and fluorescein angiography showed no abnormalities. Combining multimodal imaging is expected to improve diagnostic accuracy.
The natural course of deposits can involve rapid changes over several months or regression and resorption over several years.
Given the geographic and ethnic clustering, genomic and biomolecular analyses to elucidate the etiology are considered major future research directions. 1)
There are currently no reports that crystal deposits in WACM themselves cause visual impairment. 1) The prognosis is generally good, and deposits may spontaneously regress over several years. However, concurrent retinal vascular diseases such as diabetic retinopathy can affect vision, so management of systemic diseases and regular ophthalmologic follow-up are important.
