A macular cherry-red spot is a pathognomonic ocular manifestation of central retinal artery occlusion, traumatic retinal edema, and various forms of lysosomal storage diseases, such as GM1 gangliosidosis, Niemann–Pick disease, sialidosis, and galactosialidosis. Galactosialidosis is characterized by decreased ß-galactosidase and sialidase activity. It is transmitted as an autosomal recessive trait and is caused by a mutation in the cathepsin A (CTSA) gene.1,2 The clinical manifestations of this disease are heterogeneous: myoclonus, cerebellar ataxia, skeletal dysplasia, mental retardation, and visual disturbances. The juvenile/adult form, however, often has less severe systemic manifestations. The ocular manifestations, including corneal clouding and macular cherry-red spot, can be keys to diagnosis.2
We present the fundus autofluorescence (FAF) findings in a patient with genetically confirmed galactosialidosis. No similar images have been published.
The patient noticed visual disturbances at the age of 16 years and consulted a local ophthalmologist, who detected a macular cherry-red spot ophthalmoscopically. At the age of 19 years, the patient was referred to our hospital for a more detailed ocular examination. He had no systemic abnormalities, and laboratory tests revealed no particular abnormalities except for a slight decrease in ß-galactosidase and sialidase activities. The activities, measured in lymphocytes, were 25 nmol/mg protein/h (control: 120) for ß-galactosidase and 2 nmol/mg protein/h (control: 6) for sialidase. Genetic analysis revealed a homozygous intronic change in the CTSA gene (c.746 + 3A > G), which was reported to cause a skipping of exon 7 in the mRNA.2
The patient’s best corrected visual acuity was 0.3 for both eyes, and Goldmann perimetry revealed a relative central scotoma bilaterally. Slit lamp examination showed no clouding of the cornea, and funduscopic examination revealed a macular cherry-red spot bilaterally (Figure 1A, page 260). Optical coherence tomography (OCT) with the Cirrus HD-OCT, version 5.1 (Carl Zeiss Meditec, Jena, Germany), showed an abnormal hyperreflectivity in the retinal ganglion cell (RGC) layer, which made it difficult to differentiate the RGC layer from the nerve fiver layer (Figure 2, asterisks; page 260). The thickness of both the RGC and nerve fiber layers were normal, and the appearances of outer retinal structures were also within normal limits.
Fundus photographs and fundus autofluorescence (FAF) images. (A) Fundus photographs showing cherry-red spot in both maculas. (B) FAF images showing abnormal hyper-autofluorescence in the macula. The lesion seen in the FAF has expanded over that seen in the fundus photograph (arrows).
Optical coherence tomography (OCT) of a normal subject and a patient with galactosialidosis. The retinal ganglion cell layer (GCL) appears hyperreflective in the macula, and the boundary between the nerve fiber layer (NFL) and the GCL is unclear (asterisk). IPL = inner plexiform layer.
FAF images were recorded with 488-nm wavelength using a barrier filter for the detection of emitted light above 500 nm (HRA2; Heidelberg Engineering, Heidelberg, Germany). A clearly demarcated hyperreflective region was detected in the macula, which spared the fovea in both eyes (Figure 1B). The region of FAF abnormality overlaid not only the cherry-red spot but also areas appearing normal ophthalmoscopically (Figure 1, arrows).
Our results demonstrated that FAF can detect a hyper-autofluorescent lesion more clearly than conventional ophthalmoscopic examination. In the OCT image, an abnormally hyperreflective region could be detected in the RGC layer; however, the boundary between hyperreflective and normal regions was not clear.3 We have searched PubMed with the terms “cherry red spot” and “autofluorescence” and confirmed that no published study has described similar features.
Histolopathological investigations of the retina of a patient with the late-infantile type of galactosialidosis showed a markedly decreased number of ganglion cells throughout the retina. In addition, the remaining ganglion cells were swollen. Histopathological staining showed abnormal deposits containing phopholipids, proteinaceous material, and lipofuscin-like substances accumulated in the RGCs and amacrine cells.4
Lipofuscin granules have been found in the brain and other organs in other diseases with a macular cherry-red spot.5–7 Lipofuscin is the primary source of retinal autofluorescence detected by 480-nm excitation, and the hyper-autofluorescence in the macular region may represent an accumulation of storage materials, such as lipofuscin, in the RGC layer.4
A cherry-red spot may not be apparent at the early stage and in less symptomatic types of various storage diseases.4,8 The cherry-red spot is also known to disappear at the late stages of some diseases.4 In such cases, FAF may be potentially more sensitive for the detection of macular lesions. Our results indicate that FAF may be a useful method to detect macular lesions in patients with galactosialidosis and other lysosomal storage diseases.
- Zhou XY, Galjart NJ, Willemsen R, Gillemans N, Galjaard H, d’Azzo A. A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable. EMBO J. 1991;10(13):4041–4048.
- Shimmoto M, Fukuhara Y, Itoh K, Oshima A, Sakuraba H, Suzuki Y. Protective protein gene mutations in galactosialidosis. J Clin Invest. 1993;91(6):2393–2398. doi:10.1172/JCI116472 [CrossRef]
- Heroman JW, Rychwalski P, Barr CC. Cherry red spot in sialidosis (mucolipidosis type I). Arch Ophthalmol. 2008;126(2):270–271. doi:10.1001/archophthalmol.2007.31 [CrossRef]
- Usui T, Sawaguchi S, Abe H, Iwata K, Oyanagi K. Late-infantile type galactosialidosis. Histopathology of the retina and optic nerve. Arch Ophthalmol. 1991;109(4):542–546. doi:10.1001/archopht.1991.01080040110040 [CrossRef]
- Allegranza A, Tredici G, Marmiroli P, di Donato S, Franceschetti S, Mariani C. Sialidosis type I: pathological study in an adult. Clin Neuropathol. 1989;8(6):266–271.
- Yamamoto A, Adachi S, Kawamura S, Takahashi M, Kitani T. Localized beta-galactosidase deficiency. Occurrence in cerebellar ataxia with myoclonus epilepsy and macular cherry-red spot--a new variant of GM1-gangliosidosis?Arch Intern Med. 1974;134(4):627–634. doi:10.1001/archinte.1974.00320220029002 [CrossRef]
- Rapin I, Goldfischer S, Katzman R, Engel J Jr, O’Brien JS. The cherry-red spot--myoclonus syndrome. Ann Neurol. 1978;3(3):234–242. doi:10.1002/ana.410030309 [CrossRef]
- Kivlin JD, Sanborn GE, Myers GG. The cherry-red spot in Tay-Sachs and other storage diseases. Ann Neurol. 1985;17(4):356–360. doi:10.1002/ana.410170409 [CrossRef]