Ocular development after highly effective modulator treatment early in life

Area of Science:

• Pharmacology
• Ophthalmology
• Genetics

Background:

• Highly effective CFTR modulator therapies (HEMT) have transformed cystic fibrosis care, improving clinical outcomes and quality of life for many individuals.
• Increased pregnancies in women with CF are observed due to improved health, necessitating evaluation of HEMT safety during gestation and lactation.
• HEMT are known to cross the placenta and enter breast milk, raising concerns about potential infant toxicity.

Purpose of the Study:

• To review existing evidence on the impact of HEMT on lens development during pregnancy and breastfeeding.
• To explore the mechanisms by which HEMT might influence normal and abnormal lens development.
• To identify critical unanswered questions regarding HEMT exposure and infant ocular health.

Main Methods:

• Literature review of preclinical toxicity studies and clinical case reports on HEMT exposure during pregnancy and lactation.
• Analysis of data concerning HEMT transfer across the placenta and into breast milk.
• Synthesis of information on lens development and potential HEMT-induced cataracts.

Main Results:

• Toxicity studies in rats indicated a risk of infant cataracts following HEMT exposure.
• Case reports suggest a correlation between early-life HEMT exposure and congenital cataracts.
• HEMT are confirmed to be transferred to the fetus and infant via maternal therapy.

Conclusions:

• HEMT exposure during pregnancy and breastfeeding warrants careful consideration due to potential risks of infant cataracts.
• Further research is crucial to elucidate the precise mechanisms and long-term effects of HEMT on infant ocular development.
• Clinical monitoring and risk-benefit assessments are essential for pregnant and breastfeeding individuals with CF on HEMT.