Cherry-red spot

A cherry-red spot is a finding in the macula of the eye in a variety of lipid storage disorders and in central retinal artery occlusion.[1] It describes the appearance of a small circular choroid shape as seen through the fovea centralis. [2] Its appearance is due to a relative transparency of the macula; storage disorders cause the accumulation of storage material within the cell layers of the retina, however, the macula, which is relatively devoid of cellular layers, does not build up this material, and thus allows the eye to see through the macula to the red choroid below.

Differential diagnosis of cherry-red spot at macula

1. Metabolic Storage Diseases: 1. Mucopolysaccharidosis 2. Hurler's disease 3. Tay-Sachs disease 4. MPS VII (Sly syndrome) 5. Farber's disease 6. GM1 gangliosidoses 7. Niemann Pick's disease 8. Sandhoff disease 9. Shprintzen-Goldberg syndrome 10. Lysosomal Storage Diseases 11. Sialidosis Type 1 2. Congenital Developmental Diseases : Leber's Congenital Amaurosis 3. Hereditary/ Familial: 1. Hallervorden Spatz disease 2. Krabbe disease 4. Degenerative: Metachromatic leukodystrophy 5. Vascular: Central retinal artery occlusion 6. Drugs: 1. Quinine toxicity 2. Dapsone toxicity 7. Poisoning: 1. Carbon monoxide 2. Methanol Cherry-red spot at macula

Pathogenesis
A cherry-red spot at the macula (Fig. 15.58) is a clinical sign seen in the context of thickening and loss of transparency of the retina at the posterior pole. The fovea, being the thinnest part of the retina and devoid of ganglion cells, retains relative transparency, allowing persistent transmission of the underlying highly vascular choroidal hue. This striking lesion occurs in the sphingolipidoses, which comprise a group of rare inherited metabolic diseases characterized by the progressive intracellular accretion of excessive quantities of certain glycolipids and phospholipids in various tissues of the body, including the retina. The lipids accumulate in the ganglion cell layer of the retina, giving the retina a white appearance. As ganglion cells are absent at the foveola,

this area retains relative transparency and contrasts with the surrounding opaque retina. With the passage of time the ganglion cells die and the spot becomes less evident. The late stage of the disease is characterized by degeneration of the retinal nerve fibre layer and consecutive optic atrophy. The following diseases are associated with a cherry-red spot.

Mucopolysaccharides
Mucopolysaccharides consist of glycosaminoglycans attached to a link protein with a hyaluronic acid core. Lysosomal enzymes degrade these macromolecules into smaller components. Heparan sulfate, dermatan sulfate, and keratan sulfate are by-products of an incomplete degradation process. The accumulation of these compounds interferes with cell function. Defective activity of the lysosomal enzymes blocks the degradation process of mucopolysaccharides, leading to abnormal accumulation of heparan sulfate, dermatan sulfate, and keratan sulfate. These degradation by-products are then secreted and detected in the urine. Mucopolysaccharidosis (MPS) can be subclassified according to the type and amount of substance that accumulates, as follows: Hurler syndrome (MPS IH), Hurler-Scheie (MPS I-H/S), Scheie syndrome (MPS IS), Hunter syndrome (MPS II), Sanfilippo syndrome (MPS III), Morquio syndrome (MP IV), Maroteaux-Lamy syndrome (MPS VI), and Sly syndrome (MPS VII)

GM1 gangliosidosis (generalized)

1 2 3 4 1 2 Inheritance is AR. Defect. Deficiency of beta-galactosidase 1. Systemic features include coarse facies, stiff joints, growth deficiency and severe cerebral degeneration leading to death by the age of 2 years. Ocular features are macular cherry-red spot in 50% of cases and very subtle corneal clouding. Inheritance is AR. Systemic a Late-onset (after the age of 7 years) with myoclonus and seizures, compatible with normal life span. b Severe starts before the age of 2 years and is characterized by severe neurodegeneration Hurler-like facies, hepatosplenomegaly, deafness, severe neurodegeneration and death in early childhood.

Mucolipidosis type I (sialidosis)

Ocular features include corneal clouding, macular cherry-red spot, optic atrophy and occasionally punctate lens opacities. GM2 gangliosidosis

TaySachs disease
1 2 Inheritance is AR. Pathogenesis. Deficiency of hexosaminidase A leads to accumulation of GM2 ganglioside in the brain and retina.

3 4

Systemic features are progressive neurological deterioration starting within 6 months or birth with death by 24 years. Ocular features include a macular cherry-red spot that is present by 3 months and optic atrophy after 1 year, with blindness by the age of 2 years. Inheritance is AR. Pathogenesis. Hexosaminidase A and B deficiency. Systemic features. Neurological degeneration similar to TaySachs disease. Ocular features are macular cherry-red spot and early-onset blindness.

Sandhoff disease
1 2 3 4

NiemannPick disease
There are three main types of Niemann disease (AC) but only the first two are associated with a cherry-red spot. The main ocular features of type C (chronic neuropathic) are gaze palsy and abnormal eye movements. Niemann-Pick disease is an autosomal recessive lipidosis due to impaired sphingomyelin metabolism. Sphingomyelin is a constituent of many cell membranes and a major lipid of the myelin sheath and of the stroma of red blood cells. Sphingomyelin is normally metabolized by the cleavage of phosphorylcholine from ceramide by the action of the enzyme sphingomyelinase. This enzyme is deficient in Niemann-Pick disease type A and type B. The two types are believed to be allelic.39 In Niemann-Pick disease type C, sphingomyelinase activity is usually normal; the metabolic block is said to be in the esterification of cholesterol within the cells.40 The biochemical defects in Niemann-Pick disease type D and in type E remain to be discovered. Type A (acute neuronopathic) 1 Inheritance is AR. 2 Systemic features present in infancy and are characterized by severe psychomotor deterioration, massive hepatosplenomegaly and death by the 4th year. 3 Ocular features are macular cherry-red spot in 50% and subtle corneal clouding. Type B (chronic non-neuronopathic) 1 Inheritance is AR. 2 Systemic features present in the teenage years or early adulthood and are characterized by hepatosplenomegaly, and involvement of lungs and bone marrow. CNS disease does not occur and survival for up to 20 years after presentation is possible. 3 Ocular features are macular cherry-red spot and bull's eye maculopathy.

Farber disease
1 2 3 4 Inheritance is AR. Pathogenesis. Lysosomal storage disease due to defective ceramidase. Systemic features include hoarseness, aphonia, dermatitis, lymphadenopathy, psychomotor retardation, and renal and cardiopulmonary disease. Ocular features include macular cherry-red spot, pingueculum-like conjunctival lesions and nodular corneal

opacity. Shprintzen-Goldberg syndrome is a multiple anomaly syndrome that has craniosynostosis, multiple abdominal hernias,
cognitive impairment, and other skeletal malformations as key features

Krabbe's disease

The metabolic block is a severe deficiency of the enzyme galactocerebroside--galactosidase, which normally breaks down galactocerebroside to ceramide and galactose. It is postulated that the accumulation of galactocerebroside and its deacylated derivative psychosine results in the destruction of myelin-producing cells, the oligodendroglia, causing dysmyelination and a widespread leukodystrophy. The total brain content of galactocerebroside is not increased. There are three forms of Krabbe's disease classified according to the age at onset: infantile, juvenile, and adult. TABLE 2. Storage Diseases with Macular Cherry-Red Spots Disease GM2-gangliosidosis Tay-Sachs disease Sandhoff's disease AB variant B1variant Hex A deficient Hex A and B deficient Hex A, B normal Leukocyte serum Leukocyte serum GM2loading studies in fibroblasts Leukocyte serum Leukocyte fibroblasts Leukocyte fibroblasts Leukocyte fibroblasts Leukocyte fibroblasts Fresh fibroblasts Enzyme Diagnostic Sample(s)

Hex A deficient with sulfated substrate Leukocyte fibroblasts

Juvenile GM2-gangliosidosis Partial Hex A deficiency Infantile GM1-gangliosidosis -Galactosidase deficient Niemann-Pick disease Type A, infantile Type B Sialidoses Type 1 Type 2 Sialidase deficient Sphingomyelinase deficient Sphingomyelinase deficient

Farber's lipogranulomatosis Ceramidase

Sialidase and -galactosidase deficient Fresh fibroblasts