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Earlier Vision Loss in Children With Leber’s Disease Tied to Better Long-Term Visual Outcomes

NEW YORK (Reuters Health) – Children whose onset of Leber’s hereditary optic neuropathy (LHON) occurs before they’re 13 years old have better long-term visual outcomes than those with onset between 13 and 16, researchers in Germany report.

“LHON with childhood onset before the age of 13 years is associated with a milder course of disease as compared with early-teenage onset,” the team reports in the British Journal of Ophthalmology. “This difference seems to largely rely on a greater capacity for recovery in childhood onset LHON patients in the better eye.”

“The data of our study do not only improve patient counselling, but should also have a great impact on the design of future clinical trials examining new investigational therapies in children, as well as on the real-life appraisal of currently approved treatment approaches,” they add.

Around 80% of cases of this rare mitochondrial neurodegenerative disease are thought to occur in males, with onset usually between 16 and 35 year of age. Recent studies suggest that LHON is diagnosed after age 45 in 8% to 14% of patients, and by age 12 in 11%.

To investigate the clinical characteristics of patients age 16 and younger, Dr. Claudia S. Priglinger of Ludwig Maximilian University of Munich and her colleagues analyzed registry data from the German network for mitochondrial disorders, mitoNET.

The researchers included patients with LHON onset between ages 4 and 16 who had at least four years of follow-up without treatment. They compared visual acuity (VA) at baseline, lowest VA ever recorded (nadir), and VA at the end of follow-up between childhood-onset (through age 12 years) and early-teenage-onset disease (age 13 through 16 years).

Of the 231 patients with LHON, 11 patients in the childhood-onset group and eight patients in the early-teenage-onset group met inclusion criteria. The mean age was 8.6 years in the childhood-onset group and 15.4 years in the early-teenage-onset group. Follow-up averaged 184 months in the childhood-onset group and 119 months early-teenage-onset group.

Baseline VAs were not significantly different between the two groups in better and worse eyes, respectively. In worse eyes, both groups showed a similar deterioration (P=0.79) to nadir and a similar recovery through the end of follow-up (P=0.38).

In better eyes, both groups deteriorated similarly (P=0.16) to nadir. From nadir through the end of follow-up, better eyes in the childhood-onset group showed significantly better recovery than better eyes in early-teenage-onset group (-0.35 vs. -0.01 logMAR; P=0.02).

Dr. Amanda D. Henderson, an assistant professor of ophthalmology at Johns Hopkins University School of Medicine and the chief of the Neuro-Ophthalmology Division at Johns Hopkins Wilmer Eye Institute in Baltimore, Maryland, welcomed the research.

“This study provides additional prognostic information to counsel young patients and their families affected by LHON,” she told Reuters Health by email. “The information from this study could also be important when selecting inclusion groups for and interpreting results from future clinical trials, such as gene therapy trials.”

“One notable strength is that no patient included in this study was affected solely by the 14484 mutation, which is known to have a better visual prognosis than the other major mutations,” Dr. Henderson said. “Additionally, the authors conducted a secondary analysis that excluded the two patients affected by a combination of the 14484 and 11778 mutations and found that the results were unchanged.”

“Weaknesses of this study include its retrospective nature and its small sample size, which is often inherent in the study of rare diseases,” added Dr. Henderson.

Dr. Eric D. Gaier, an assistant professor of ophthalmology at Harvard Medical School and a pediatric neuro-ophthalmologist at Massachusetts Eye and Ear in Boston, called the study “an important and innovative contribution that advances our understanding of a devastating, blinding disease.”

“Conversations I have with families that carry or are already affected by LHON variants are often centered on what to expect if or after vision loss occurs,” Dr. Gaier, who also was not involved in the study, told Reuters Health by email. “The paucity of data and uncertainty makes these conversations particularly challenging when it comes to children.”

“Younger patients faring better than older patients, as we often see in other neurologic disorders, is not so surprising, but kids’ capacity for plasticity always amazes me,” he said. “The magnitude of effect the authors demonstrate despite a relatively small number of patients is striking and carries high clinical significance.”

“The authors provide a critical piece to the puzzle that will help me provide a relatively positive evidence-based perspective when it comes to younger children with LHON,” Dr. Gaier noted. “Defining LHON’s age-dependent natural course also helps us prioritize and balance risk when considering new treatments.”

Dr. Priglinger did not respond to requests for comment.

SOURCE: https://bit.ly/3Jnnael British Journal of Ophthalmology, online February 21, 2022.

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