Zou et al.

BMC Ophthalmology (2016) 16:30

DOI 10.1186/s12886-016-0201-9

CASE REPORT Open Access

Fundus autofluorescence and optical

coherence tomography of a macular
cherry-red spot in a case report of sialidosis
Wenjun Zou1, Xin Wang2 and Guohong Tian2*

Abstract
Background: Sialidosis is a rare lysosomal storage disorder characterized by deficiency of alpha-N-acetyl neuraminidase.
The macular cherry-red spot, which could be important for diagnosis, is a distinctive feature of its ocular manifestation.
We evaluated the fundus autofluorescence (FAF) and optical coherence tomography (OCT) images of a juvenile patient
who presented with vision decrease and was later confirmed with genetic sialidosis.
Case presentation: A 13-year-old Chinese male presented with bilateral decreased vision over the past 2 years before
his initial visit. Funduscopic examination revealed a macular cherry-red bilateral spot. FAF showed hyperreflective areas
surrounding a central hyporeflective fovea in both eyes. OCT revealed increased reflectivity in the ganglion cell layer in
both maculae without a definite boundary between the hyperreflective and normal areas. These findings suggested that
lipofuscin had accumulated in the retinal ganglion cells, which is a distinctive ocular feature in metabolic central nervous
system (CNS) disorders. He was later confirmed with genetic sialidosis.
Conclusions: FAF and OCT images are very sensitive and useful techniques for diagnosing lysosomal storage disease of
the CNS, and are helpful in evaluating the extent of damage in retinal ganglion cells.
Keywords: Sialidosis, Cherry-red spot, Fundus autofluorescence, Optical coherence tomography

Background storage diseases [5]. We evaluated the fundus autofluo-

The macular cherry-red spot was first named by Bernard rescence (FAF) and the optical coherence tomography
Sachs. It is a very distinctive ocular manifestation of (OCT) imaging in a juvenile patient presenting with a
central retinal artery occlusion, traumatic retinal edema, vision decrease, who was later confirmed with genetic
and many neurological metabolic disorders such as sialidosis.
Sandhoff disease, galactosialidosis, GM1 and GM2 gang-
liosidosis, and sialidosis types I and II [1]. Sialidosis is a Case presentation
rare lysosomal storage disorder characterized by defi- A 13-year-old Chinese male complained of vision de-
ciency of alpha-N-acetyl neuraminidase. It is transmitted creased over the past 2 years, and had an unbalanced gait
as an autosomal recessive trait and is caused by a muta- as reported by his parents. He was a high school student
tion in the neuraminidase (NEU) gene. There is a wide with normal intelligence and without smoking or alcohol
clinical spectrum ranging from nearly asymptomatic to abuse. His past medical history and family history were
severe presentations. The clinical features of sialidosis unremarkable. A neuro-ophthalmological examination
type I include late-onset, cerebellar ataxia, myoclonic revealed the patient to be alert and oriented. The best-
epilepsy, nystagmus, as well as progressive visual loss corrected visual acuities (BCVA) were 20/100 OU. Color
[2–4]. The macular cherry-red spot is a very distinctive vision (Ishihara plates) was 1/8 OU. Slit lamp examination
ocular feature for differential diagnosis of various CNS showed a punctate cataract and funduscopic examination
revealed macular bilateral cherry-red spots and normal
* Correspondence: valentian99@hotmail.com optic discs (Fig. 1). There was no nystagmus. The deep
2
Department of Ophthalmology, Eye Ear Nose and Throat Hospital, Fudan
University, 83 Fenyang Road, Shanghai 200031, China tendon reflexes were generally decreased with ataxia and
Full list of author information is available at the end of the article slight myoclonus of the upper and lower limbs.
© 2016 Zou et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Zou et al. BMC Ophthalmology (2016) 16:30
Fig. 1 Fundus photographs, showing a cherry-red spot in both maculae
FAF images (Heidelberg Engineering, Heidelberg,
Germany) showed a patch of hyperreflective areas sur-
rounding a hyporeflective fovea in both eyes (Fig. 2).
OCT revealed increased reflectivity in the ganglion cell
layer in both maculae, which corresponded to the
hyperreflective areas on FAF; however, the boundaries
between the hyperreflective and normal regions were
not clear (Fig.3).
Laboratory test results showed normal levels of β-
galactosidase, hexosaminidase A and B, arylsulfatase A,
and β-galactocerebrosidase. Genetic analysis revealed
two compound heterozygous mutations in the NEU1
gene.
Because there was no treatment for sialidosis, the pa-
tient was only followed-up by his ophthalmologist and
neurologist. His visual function was stable after a follow-
up of 1 year.
Conclusions
Sialidosis is a rare autosomal recessive disorder resulting
from a deficiency of alpha-N-acetyl neuraminidase caused
by a mutation in the NEU gene located on 6p21.33. This
results in abnormal intracellular accumulation of sialyloli-
gosaccharides, especially in brain neurons and in ganglion
Fig. 2 Fundus autofluorescence (FAF) imaging, showing bilateral hyperreflective areas surrounding the fovea
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 2 of 3
cells of the retina. A definitive diagnosis involves confirm-
ation of a NEU gene mutation or a deficiency of neuramin-
idase activity in leukocytes and cultured fibroblasts using
skin biopsies [2, 3].
Sialidosis is clinically classified as two major pheno-
types: type I, a cherry-red spot myoclonus syndrome
without dysmorphism, and type II, a more severe infant-
ile form with dysmorphism [4]. Our case presented with
bilateral cherry-red spots and myoclonus without mental
deterioration and dysmorphism, which was consistent
with type I.
The retinal ganglion cells are part of the CNS neurons.
Retinal ganglion cell microstructure can be observed
using an ophthalmoscope or by OCT. In the OCT
images of the patient, abnormal hyperreflective areas
were detected in the ganglion cell layer; however, the
boundaries between the hyperreflective areas and the
normal retinas were not clear [6, 7]. FAF imaging of the
patient revealed bilateral hyperautofluorescent lesions
surrounding a small hyporeflective center, the fovea.
Because lipofuscin, which can be detected by excitation
at 488 nm, is the primary source of retinal autofluores-
cence, the hyperreflective areas in retinal lesions indicate
intracytoplasmic accumulation of lipofuscin-like granules
Zou et al. BMC Ophthalmology (2016) 16:30
Fig. 3 Optical coherence tomography (OCT) imaging, showing thickening and increased reflectivity in the ganglion cell layer (GCL) in bilateral
eyes. The boundary between the GCL and the nerve fiber layer (NFL) is unclear. IPL = inner plexiform layer
from a metabolic disease such as sialidosis [8]. There are
two interpretations for the retinal cherry-red spots in siali-
dosis. One is the deposition of lipofuscin granules in the
ganglion cell layer in the perifoveal areas that result in a
white patch around the fovea. Alternatively, the foveal pit
lacks ganglion cells, and thus continues to maintain its
reddish appearance [9].
In conclusion, when evaluating a patient with a
cherry-red spot in the macula, which is not due to arter-
ial occlusion or trauma, the diagnosis should consider
various forms of lysosomal storage diseases. It is import-
ant to note that ophthalmic images using FAF and OCT
are very sensitive and useful methods for detecting
neurological metabolic disorders presenting with a
cherry-red spot in the macula.
Consent
Written informed consent was obtained from the par-
ents (because the patient was under 16 years of age) for
publication of this case and any accompanying images.
A copy of the written consent is available for review by
the editor of this journal.
Abbreviations
BCVA: best corrected visual acuities; CNS: central nervous system;
FAF: Fundus autofluorescence; GCL: ganglion cell layer; IPL: inner plexiform
layer; NEU: neuraminidase; NFL: nerve fiber layer; OCT: optical coherence
tomography.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
WJZ and GHT reviewed the literature and drafted the manuscript. XW
participated in the collection of clinical information. GHT interpreted the
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 3 of 3
data, and critically reviewed the manuscript finally. All authors read and
approved the final manuscript.
Acknowledgement
The authors thank Dr. gezhi Xu, Dr. Wenji Wang and Dr. Qing Chang for
evaluating the case together.
Author details
1
Department of Ophthalmology, Nanjing Medical University Affiliated Wuxi
Second Hospital, Wuxi 214002, China. 2Department of Ophthalmology, Eye
Ear Nose and Throat Hospital, Fudan University, 83 Fenyang Road, Shanghai
200031, China.
Received: 26 September 2015 Accepted: 28 February 2016
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