Vision Loss, Retinal Nerve Fiber Layer Thinning Experienced in Wolfram Syndrome

Children with Wolfram syndrome experience vision loss and retinal nerve fiber layer (RNFL) thinning, according to research published in the American Journal of Ophthalmology.

Researchers included 38 children (mean age, 13.26±5.53 years; 42% boys) with Wolfram syndrome in a single center cohort analysis. All participants underwent comprehensive ophthalmic examination and optical coherence tomography (OCT) imaging annually with a mean follow up duration of 6.44 years. The study objective was to determine long-term rates of visual decline, macular thinning, RNFL thinning and outer plexiform lamination (OPL) in children with Wolfram syndrome.

Overall, visual acuity declined a mean 0.059 logarithm of the minimum angle of resolution (logMAR) per year (95% CI, 0.07-0.05 logMAR/year). A total of 25% of participants experienced rapid vision loss (mean vision loss, 0.16±0.05 logMAR/year). More rapid vision loss was associated with earlier onset of diabetes mellitus (mean age, 4.7±1.01 years; P =.03) and optic atrophy (mean age, 7.7±2.26 years; P =.003).

Mean initial macular volume decreased by 0.038 mm³ per year, and inner and outer macular layers decreased at rates of -1.19 µm/year and -1.14 µm/year, respectively. 

Inferior RNFL thickness decreased most rapidly ( β = −0.98 µm/y) compared with the superior (β = −0.5 µm/y) and nasal quadrants (β = −0.28 µm/y).

Researchers identified OPL in 3 study participants. Two of those individuals had autosomal dominant mutations, and 1 had autosomal recessive mutations.

“Although most [children with Wolfram syndrome] experienced gradual vision decline, a subset were noted to have more rapid vision loss which was associated with earlier diagnosis of diabetes and optic atrophy,” according to the researchers. “Our anatomic data revealed several participants with OPL lamination, which was not limited to those with autosomal dominant disease and not associated with greater rates of vision loss.”

Study limitations include a lack of ophthalmic disease development analysis before diagnosis and retinal layer segmentation measurement error.