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By Lucy Piper, Senior medwireNews Reporter

Researchers have found that children with achromatopsia have milder foveal pathology than their older counterparts, highlighting a potential opportunity for early intervention with gene therapy.

“Hopefully, gene therapy would not only stabilize retinal architecture and prevent progression of abnormal foveal morphology but also reduce photophobia and improve visual acuity”, the team comments in JAMA Ophthalmology.

In all, nine children with achromatopsia, aged an average of 4.2 years, participated in the study and were compared with nine similarly aged children without the condition.

The patients had a history of decreased vision, nystagmus and photophobia. Seven had no cone response on full-field electroretinography, while two had a severely attenuated cone response. Rod response was normal in seven patients and mildly abnormal in two.

Handheld spectral domain–optical coherence tomography (SD-OCT) identified foveal ellipsoid zone disruption in six (67%) of the patients and foveal hypoplasia in four (44%). Foveal ellipsoid zone disruption was relatively mild in most patients, but one patient was found to have a foveal hyporeflective zone and another to have complete loss.

The total retinal thickness of the macula in the patients was on average 38.8 µm (14%) thinner than that in controls and the total retinal thickness of the fovea was 42.2 µm (17%) thinner.

In both cases, this was primarily due to differences in the thickness of the outer retina, which was 18% thinner in the macula of patients than of controls and 26% thinner in the fovea. The researchers say this suggests that either cone photoreceptor atrophy begins in early childhood or shortened photoreceptors are a congenital characteristic of abnormal cone morphology in achromatopsia.

They note that the patients with the most normal-appearing foveal ellipsoid zone architecture were also those with the most preserved foveal photoreceptor cell body layer. These individuals “would likely benefit the most from future gene therapy clinical trials”, say researcher Mark Pennesi (Oregon Health Science University, Portland, USA) and colleagues.

They add that their findings highlight the use of handheld SD-OCT for assessing children with achromatopsia on finding that neither age alone, nor genotyping predicted the degree of photoreceptor loss or preservation.

The researchers report that the worst-affected patient was the youngest patient, who carried compound heterozygous mutations in CNGB3 and a single mutation in CNGA3.

“It is likely that clinical benefit would vary, but it is possible that among the patients with good foveal architecture, those with worse visual acuity may have the most to gain from treatment”, they conclude.

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