Compared to children whose vision loss is due to Stargardt disease, those with juvenile Batten disease (CLN3) have a more extensive retinal pathology resulting in significantly faster loss of visual acuity, color blindness and poor retinal responses to light, according to a study.
Recognizing the early clinical features of Batten disease, which may be similar to those of early-onset Stargardt (STGD1), can help clinicians make an accurate diagnosis and start appropriate treatment.
According to the researchers, this analysis – performed in children with obvious macular degeneration around the age of 6 – is “the most comprehensive overview of the ophthalmologic features of early Batten disease described so far.”
The study, “Recognize the differentiating clinical signs of CLN3 disease (Batten disease) during presentation, ”Was published in Acta Ophthalmologic.
Young Batten’s symptoms are similar to those of early-onset STGD1, a rare unrelated genetic disorder that causes vision loss due to macular degeneration.
The lack of distinctive clinical features makes the diagnosis of Batten difficult, often resulting in a diagnostic odyssey that delays the onset of appropriate care for this serious metabolic disorder, and the possibility of better outcomes for patients and their families.
Researchers in the Netherlands sought to identify clinical features that might distinguish juvenile Batten disease from early-onset STGD1.
The clinical data of 38 children with rapid vision loss, referred to a specialized eye center between 1987 and 2019, were reviewed. Visual acuity was assessed using the best corrected visual acuity (MAVC) of both eyes (VODS), where a lower VODS indicates worse vision.
Of these 38 patients, 18 were later diagnosed with Batten disease and 20 with early-onset STGD1. Children with Batten disease had a slightly earlier age of onset (mean age, 6.4) while the mean age of those with STGD1 was 7.5. Visual acuity loss was more pronounced at baseline in Batten than in STGD1 patients, with mean VODS of 0.2 and 0.3, respectively.
The slight differences in age and visual clarity at the start were not sufficient to differentiate the diseases, and clinically significant overlap was observed.
During the first year after disease onset, however, the loss of visual acuity in Batten disease progressed significantly more rapidly than in early-onset STGD1.
“[W]Hi VA [loss of visual acuity] itself may not be clearly different between early-onset CLN3 and STGD1 disease upon presentation, the rate of vision loss is clearly different – already within the first year of follow-up, ”the researchers wrote.
Color vision problems, particularly red-green color blindness, were also much more severe in Batten’s patients, distinguishing most of these children from those with STGD.
The tritan (blue-green) color vision deficit was also more severe in Batten, but not to the same degree as the red-green color vision loss.
Batten’s degree of visual acuity and color blindness was large enough to distinguish the disease from early-onset STGD1, the researchers noted.
The presence of pale optic discs – a sign of optic atrophy – and narrowed retinal arteries were observed in 70.5% and 88.2% of Batten patients tested, respectively, compared to 10% and 10.5% of patients. Early-onset STGD1. (Optic discs represent the start of the optic nerve and are also the entry point for the major blood vessels that supply the eye).
While the outer photoreceptor layer of the retina was severely affected in both cases, only Batten patients had internal retinal abnormalities. (The retina is the innermost, light-sensitive layer of tissue in the eye, thanks to the presence of light-sensitive photoreceptors.)
A full-field electroretinogram (ERG) was used to analyze the electrical activity of the retina in response to light stimuli. The seven young Batten patients tested exhibited a distinct abnormal electrical response suggesting retinal dysfunction, including significantly reduced or absent responses to specific dark-adjusted flashes of light. No such abnormalities were observed in 11 early-onset STGD1 patients tested, in whom the ERG response was normal or only slightly reduced.
“It is important to distinguish between CLN3 disease and early-onset STGD1, a dark-adapted ERG should be included” as a diagnostic test, the study said.
These data also suggest that these observed abnormalities result from dysfunction of the internal retina, in some cases prior to the characteristic Batten photoreceptor loss.
“Using a deep phenotyping approach, we revealed that compared to early-onset STGD1 … the retina in CLN3 disease is affected more widely … and more severely, resulting in several consistent clinical and electrophysiological differentiating features of the disease. CLN3, “the researchers wrote.
Three of these features, they added, “have most clearly helped us distinguish CLN3 disease from early-onset STGD1: extremely rapid vision loss, severe color vision deficit (both indicative of severe cone involvement) and absent or electronegative AD [dark-adjusted] ERG responses.
They concluded that their work “may help clinicians differentiate between two rare but clinically relevant retinal disorders… based on their clinical features only. This differentiation allows for early identification of children with CLN3 disease, which is essential for adequate referral, counseling and rehabilitation. ”