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Vision degeneration in children with CLN2 disease, also known as late childhood Batten disease, occurs the same in both eyes and appears to accelerate from ages 4 to 7, according to a recent study.

This suggests that CLN2 therapies targeted to the eyes should be given before or as early as possible during this critical time.

Additionally, the data showed that two eye tools – optical coherence tomography (OCT) and Weill Cornell Batten Ophthalmic Severity Scale (WCBS) – effectively captured the progression of vision problems over time and can be used as objective tools to assess response to treatment in future clinical trials.

The study, “Age-symmetric association of retinal degeneration in patients with Batten disease associated with CLN2, ”Was published in the journal Ophthalmology Retina.

CLN2 disease belongs to a group of disorders called neuronal ceroid lipofuscinosis (NCL), in which waste molecules build up inside cells, primarily affecting the brain and the retina – a thin layer lining the back of the eye that sends visual signals to the brain.

While the first symptoms usually appear between 2 and 4 years of age in children with CLN2 disease, vision problems tend to develop later, after the onset of motor and developmental deficits. However, OCT imaging – used to create images of the different layers of the eye – has been reported to detect signs of retinal damage in CLN2 patients as young as 2 years old.

To date, Brineura (cerliponase alfa, by BioMarin) is the only approved treatment for CNL2 disease in the United States and Europe. Despite its effectiveness in slowing the progression of motor and speech disorders in these children, its benefits on vision-related symptoms appear to be limited.

This is why “effective therapy and a better understanding of the retinal degeneration and vision loss that continues in these children is needed,” the researchers wrote.

Researchers from Weill Cornell Medicine in New York, aimed to characterize the progression of retinal problems over time in children with CLN2 disease who had not received prior treatment.

They also sought to determine the critical period for a retinal-focused intervention and the best tools to assess the natural progression of retinal-associated disease.

The team retrospectively analyzed the demographic, clinical and ocular data of 42 patients with CLN2. All had undergone a complete ophthalmologic examination under anesthesia as part of their participation in a trial (NCT01035424) designed to study the natural progression of CLN2 disease.

Vision tests included examining the background (the inner surface of the eye), fundus photography (used to collect images of fundus condition), and OCT. In addition, OCT and fundus images were scored from 1 to 5 based on the severity of retinal disease using the previously established WCBS.

Patients (24 girls and 18 boys) had a mean age of 47 months (almost 4 years) at diagnosis (range 18-67 months) and 60 months (approximately 5 years) at first eye exam (range from 30 to 103 months). ).

Both eyes of each patient were examined at least once, and 13 children underwent multiple examinations with an average follow-up period of 15.3 months.

The results showed that children with CLN2 disease had progressive, bilateral and symmetrical degeneration of the retina over time, and that this progression was faster over a critical period of 4 to 7 years.

“This suggests that [retina-specific] early intervention or ideally before this critical period can alleviate visual decline, “the researchers wrote, adding that early diagnosis of CLN2 disease can” allow sufficient time for retinal treatment before the onset of significant retinal degeneration. “.

The team also noted that the high degree of symmetrical progression between the two eyes at different stages of progression may reduce the number of participants required in a clinical trial, since the effectiveness of a therapy can be assessed in the same patient by comparing a treated patient to a non-treated eye.

In addition, compared to fundus photography, OCT seemed to better assess symmetrical damage between the two eyes and detect subtle changes in the early stages of the disease. WCBS scores based on OCT and fundus images also accurately reflected the progression of retinal degeneration.

“WCBS scores and OCT measurements may provide objective biomarkers for the efficacy of retinal-directed CLN2 gene therapy, for which the contralateral eye provides ideal control,” the researchers wrote.

The team also noted that the data supported preclinical and clinical evidence suggesting that retinal dysfunction occurs independently of neurodegeneration of the brain and spinal cord in children with CLN2 disease. This highlights the importance of better understanding the symptoms associated with vision in CLN2 disease and of working on eye-specific therapies.


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