EURETINA 2026: Retinal signs as diagnostic clues to systemic metabolic disease

The retina can be adversely impacted as a result of many inherited metabolic diseases, and the retinal findings in some cases are apparent before the systemic diagnosis is established. Speaking at the Euretina 2026 annual meeting in Vienna, Dinah Zur, MD, grouped these conditions into five categories based on their mechanism and matched each to its typical retinal findings. She is head of the Center for Retinal Degenerations and Associate Professor of Clinical Ophthalmology, Ophthalmology Division, Tel Aviv Sourasky Medical Center, Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv.

Metabolic diseases and their ocular signs

• Lysosomal storage disorders are characterized by a missing enzyme that facilitates the accumulation of material build-up in cells. Some examples are the cherry-red spot of Tay-Sachs and Niemann-Pick disease, the eye findings of the mucopolysaccharidoses, and the retinal degeneration of juvenile Batten disease. Lipid-laden ganglion cells surround the fovea in which the ganglion cell layer remains clear; this produces the cherry-red spot.

• Peroxisomal disorders result from defective fatty-acid breakdown. Adult Refsum disease presents with retinitis pigmentosa, neuropathy, and ataxia. Diagnosis rests on elevated plasma phytanic acid levels, and the condition is one of the few treatable causes, managed with dietary restriction of phytanic acid. The Zellweger spectrum is associated with early-onset, severe retinal dystrophy.

• Mitochondrial disorders cause energy failure in tissues with high metabolic demand. Zur described the case of a 7-year-old boy who failed to grow because of adrenal insufficiency; he had retinal findings that pointed to a diagnosis of Kearns-Sayre syndrome.

• Vitamin and lipid transport defects primarily cause pigmentary retinal degeneration. In abetalipoproteinaemia, the defective transport of vitamins A and E results in a retinitis pigmentosa-like degeneration. Cobalamin C disease causes early-onset bull's-eye maculopathy and nystagmus.

• Ciliopathies are disorders that result from impaired function of the primary cilium that often involve the retinal photoreceptor cells. These conditions include Bardet-Biedl, Alström, Usher, and Joubert syndromes.

Clinical takeaway

Zur summarized, “A metabolic etiology should be considered when retinal findings are bilateral, symmetrical, and otherwise unexplained. No vascular risk factors are available to explain the clinical picture. The index of suspicion rises with younger age, consanguinity, or syndromic features such as hearing loss, ataxia, or developmental delay. The retina specialist may be the first to establish the diagnosis, and a number of these conditions are treatable.”