Cherry-red spot is an ophthalmologic finding characterized by a bright red circular area at the fovea centralis, surrounded by a pale or grayish retina. This sign is most commonly detected using an ophthalmoscope and is a hallmark of certain lysosomal storage disorders, particularly in infants. It is a critical clinical clue in the early diagnosis of metabolic and storage diseases such as Tay-Sachs disease and other sphingolipidoses.

Key associations include:

• Tay-Sachs disease: Appears in >90% of affected infants.

• Sandhoff disease: Similar retinal findings with additional organomegaly.

• Niemann-Pick disease (Type A): Cherry-red spot may accompany hepatosplenomegaly.

• Central retinal artery occlusion (CRAO): Sudden monocular vision loss with retinal pallor surrounding the fovea.

Pathophysiology

The cherry-red spot arises due to retinal ganglion cell accumulation of storage material, which renders the perifoveal retina pale, while the fovea remains relatively unaffected because it contains a thin layer of ganglion cells. Key mechanisms include:

• Ganglioside accumulation in lysosomal storage disorders (e.g., Tay-Sachs, Sandhoff disease) causing retinal opacity.

• Relative sparing of foveal retina due to its lower density of ganglion cells, allowing underlying choroidal vasculature to show through, producing the red appearance.

• Metabolic enzyme deficiencies (e.g., hexosaminidase A deficiency in Tay-Sachs) lead to substrate buildup and retinal changes.

This visual pattern is also occasionally seen in other conditions, including Niemann-Pick disease and central retinal artery occlusion (CRAO), though the underlying mechanisms differ.

Examination technique

Patient Preparation

• Ensure adequate pupil dilation with mydriatics if needed.

• Use an ophthalmoscope or retinal camera for visualization.

Observation

1. Focus on the macular area, particularly the fovea centralis.

2. Identify a bright red circular spot at the center of the retina.

3. Note the surrounding retina for gray-white opacity or pallor.

Documentation

• Record laterality (unilateral or bilateral).

• Assess severity and any accompanying retinal findings (e.g., vessel attenuation).

Clinical utility

• Early diagnostic marker: Useful in infants suspected of lysosomal storage disorders.

• Indicator of systemic metabolic disease: Alerts clinicians to underlying neurodegenerative or storage disorders.

• Ophthalmologic and neurologic correlation: Guides genetic and enzymatic testing.

Clinical features

Differential Diagnosis

Diagnostic approach

• Clinical evaluation: Observe for systemic and neurologic signs.

• Ophthalmologic exam: Fundoscopy or retinal photography.

• Laboratory testing: Enzyme assays (e.g., hexosaminidase A activity for Tay-Sachs), genetic testing.

• Neuroimaging: MRI may show cerebral atrophy or white matter changes.

Management

Underlying Disorder

• No definitive cure for most sphingolipidoses; management is supportive.

• Genetic counseling for families of affected infants.

• Enzyme replacement therapy under research in selected disorders.

Supportive Interventions

• Physical and occupational therapy for developmental support.

• Nutritional support and seizure management as indicated.

• Multidisciplinary care including neurology, ophthalmology, and genetics.

Pediatric considerations

• Cherry-red spot is most clinically relevant in infants and young children with lysosomal storage disorders.

• Early detection is critical for diagnosis, counseling, and planning supportive care.

Patient counseling

• Explain that the finding indicates underlying metabolic or retinal pathology.

• Emphasize the need for comprehensive neurologic and genetic evaluation.

• Provide guidance on long-term care, prognosis, and supportive interventions.

Conclusion

Cherry-red spot is a hallmark retinal finding that can signal serious systemic metabolic disorders, particularly in infants. Recognition during fundoscopy provides a valuable diagnostic clue for lysosomal storage diseases such as Tay-Sachs and Sandhoff disease. Early detection allows timely supportive care and family counseling, even when curative treatments are limited.

References

1. Tan C, et al. Ophthalmologic manifestations of lysosomal storage disorders. Ophthalmol Clin North Am. 2015;28(4):637–651.

2. Gravel RA, et al. Tay-Sachs disease. Lancet. 2006;368:767–779.

3. Neudorfer M, et al. Cherry-red spot: clinical and biochemical correlations. Retina. 2000;20:429–435.

4. American Academy of Ophthalmology. Basic and Clinical Science Course. 2023–2024.

5. Scriver CR, Beaudet AL, Sly WS, Valle D. The Metabolic & Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill; 2001.