Shahmeer Hamid
Introduction
Gyrate atrophy of the choroid and retina is a rare, autosomal recessive metabolic disorder affecting the chorioretinal tissues. The disease is caused by mutations in the OAT gene located on chromosome 10q26, which encodes the mitochondrial enzyme ornithine aminotransferase (1).
This enzyme deficiency leads to a marked accumulation of ornithine in the plasma (10 to 20 times normal levels) and other body fluids. The toxic levels of ornithine are believed to cause RPE dysfunction and subsequent chorioretinal degeneration, although the exact pathophysiology remains a subject of research (2).
Clinical Stages
Gyrate atrophy typically follows a progressive course beginning in childhood, characterized by specific chronologic features:
Childhood (Early Onset)
● Refractive Error: Patients often present with high myopia (nearsightedness) and astigmatism in the first decade of life.
● Nyctalopia: Night blindness is an early symptom, often preceding visible fundus changes.
● Peripheral Lesions: Small, sharply demarcated, circular regions of chorioretinal atrophy appear in the mid-periphery.
Adolescence/Early Adulthood (Progression)
● Lesion Expansion: The circular atrophic patches enlarge and coalesce, spreading toward the posterior pole (scalloped borders).
● Cataract Formation: Posterior subcapsular cataracts (PSC) frequently develop in the second or third decade, significantly earlier than in the general population.
Advanced Stage
● Macular Involvement: While the macula is often spared until late in the disease, lesions eventually encroach upon the fovea, leading to loss of central vision.
● Visual Field Loss: Progressive constriction of visual fields occurs (“tunnel vision”).
● Legal Blindness: Most patients are legally blind by the fourth or fifth decade of life due to extensive chorioretinal atrophy (3).
Investigations
Diagnosis relies on a combination of clinical appearance, metabolic testing, and imaging:
● Biochemical Testing: The gold standard for diagnosis. It reveals significantly elevated plasma ornithine levels (400–1400 µmol/L vs. normal <60 µmol/L) and hyperornithinuria (excretion in urine).
● Electroretinogram (ERG): Shows diminished rod and cone responses early on, becoming extinguished as the disease progresses.
● Electro-oculogram (EOG): Consistently abnormal or extinguished.
● Optical Coherence Tomography (OCT): Useful for detecting Cystoid Macular Edema (CME) and Epiretinal Membranes (ERM), which are common complications.
● Fundus Autofluorescence (FAF): Atrophic areas appear hypoautofluorescent (dark), often surrounded by a hyperautofluorescent margin indicating active disease progression.
● Visual Fields: Confrontation or Humphrey perimetry confirms peripheral constriction (4).
Differential Diagnosis
Conditions to differentiate from Gyrate Atrophy include:
● Choroideremia: An X-linked disorder affecting males; distinguished by the absence of hyperornithinemia and a different pattern of atrophy.
● Paving Stone Degeneration: Typically non-progressive, stationary lesions found in the far periphery, not associated with metabolic defects.
● Retinitis Pigmentosa (RP): Bone-spicule pigmentation differs from the circular “punched-out” lesions of gyrate atrophy.
● Myopic Degeneration: Lacks the specific hyperornithinemia and classic scallop-bordered lesions (5).
Management
Management aims to lower ornithine levels and address ocular complications:
● Vitamin B6 (Pyridoxine): A subset of patients (B6-responders) show a reduction in plasma ornithine levels with high-dose B6 supplementation.
● Dietary Restriction: An arginine-restricted diet (arginine is a precursor to ornithine) can lower plasma ornithine levels and potentially slow disease progression, though compliance is difficult (long-term outcomes vary).
● Medical Therapy: Oral L-lysine supplementation may compete with ornithine for renal reabsorption, lowering plasma levels.
● Surgical: Cataract extraction is often required. Care must be taken due to zonular weakness and capsular fragility.
● Macular Edema: Treated with topical carbonic anhydrase inhibitors or NSAIDs (2, 6).
Prognosis
The visual prognosis is guarded. While central vision is often preserved into the fourth decade, the disease is relentlessly progressive. The development of dense cataracts and eventual macular atrophy leads to significant visual impairment. Early diagnosis and strict metabolic control (diet and B6) may slow progression, but most patients eventually reach legal blindness by age 40-50 (7).
Conclusion
Gyrate atrophy is a progressive metabolic chorioretinal dystrophy caused by ornithine aminotransferase deficiency. It is defined by the triad of high myopia, night blindness, and characteristic “punched-out” chorioretinal lesions. Diagnosis is confirmed by hyperornithinemia. While there is no cure, management focuses on metabolic control through diet and B6 supplementation to slow retinal degeneration and surgical intervention for cataracts to maintain functional vision.
References
1. Simell O, Takki K. Raised plasma-ornithine and gyrate atrophy of the choroid and retina. Lancet. 1973;1(7811):1031-1033. doi:10.1016/s0140-6736(73)90667-3
2. Kaiser-Kupfer MI, Caruso RC, Valle D. Gyrate atrophy of the choroid and retina: further experience with long-term reduction of ornithine levels in children. Arch Ophthalmol. 2002;120(2):146-153. doi:10.1001/archopht.120.2.146
3. Takki K. Gyrate atrophy of the choroid and retina associated with hyperornithinaemia. Br J Ophthalmol. 1974;58(1):3-23. doi:10.1136/bjo.58.1.3
4. Pauleikhoff L, Weisschuh N, Lentzsch A, et al. Clinical characteristics of gyrate atrophy compared with a gyrate atrophy-like retinal phenotype. Eur J Ophthalmol. 2024;34(1):79-88. doi:10.1177/11206721231178147