Temporal macular thinning associated with X-linked Alport syndrome

JAMA Ophthalmol. 2013 Jun;131(6):777-82. doi: 10.1001/jamaophthalmol.2013.1452.

Abstract

Importance: Optical coherence tomography (OCT) findings of temporal macular thinning are important in the diagnosis and prognosis of X-linked Alport syndrome (XLAS).

Objectives: To report OCT findings and severity of temporal macular thinning in a cohort with XLAS and to correlate these and other ocular findings with mutation genotype.

Design: Patients with XLAS underwent genotyping for COL4A5 mutations and complete eye examinations with retinal imaging using spectral domain OCT and fundus photography. Temporal macular thinning was calculated from OCT measurements by comparing the ratio of the retinal thickness of the temporal to the nasal subfields with a published normative database.

Setting: University departments of ophthalmology and nephrology.

Participants: Thirty-two patients from 24 families.

Main outcome and measures: Temporal thinning index calculated from spectral domain OCT scans.

Results: All study patients had a mutation associated with the X-linked COL4A5 gene. Eleven different mutations were identified. Eleven of 32 patients (34%) expressed the L1649R mutation. Of a total of 63 eyes with available OCT scans, 44 (70%) had severe pathological temporal macular thinning. The L1649R mutation was associated with the least amount of severe temporal macular thinning and later onset of renal failure.

Conclusions and relevance: Temporal macular thinning is a prominent sign associated with XLAS, suggesting that OCT measurements are essential in the diagnosis and prognosis of the disease. The L1649R mutation in the COL4A5 gene causes a relatively mild form of XLAS characterized by late-onset renal failure and less frequent, severe temporal macular thinning relative to other COL4A5 mutations. The pathological basis for the retinal abnormalities of XLAS remains to be established.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Collagen Type IV / genetics*
  • DNA Mutational Analysis
  • Diagnostic Techniques, Ophthalmological
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Macula Lutea / pathology*
  • Macular Degeneration / genetics*
  • Macular Degeneration / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Nephritis, Hereditary / genetics*
  • Nephritis, Hereditary / pathology
  • Phenotype
  • Prognosis
  • Prospective Studies
  • Renal Insufficiency / genetics
  • Severity of Illness Index
  • Tomography, Optical Coherence
  • Utah
  • Young Adult

Substances

  • COL4A5 protein, human
  • Collagen Type IV