Deep red light for ptosis in primary mitochondrial conditions in children and young people: a proof of concept study

Source abstract

Abstract Background Primary mitochondrial diseases are rare genetic disorders characterised by impaired energy production, leading to multisystem involvement, including ophthalmic manifestations such as ptosis due to levator muscle weakness. Long-wavelength red light (≈670 nm) has been shown to enhance mitochondrial function in preclinical and clinical models, but its clinical effects in children and young people (CYP) with mitochondrial disease are unknown. We carried out a proof-of-concept study to evaluate the feasibility, safety, and potential efficacy of deep red light therapy for ptosis in this population. We performed a single-centre, open-label cohort study with delayed-start design at a tertiary ophthalmology centre in the UK. CYP aged 3–17 years with genetically confirmed primary mitochondrial disease and ptosis were enrolled and randomised to immediate or delayed (3 months) initiation of once-daily 3-minute exposure to 660–670 nm light for up to 18 months. The primary outcome was change in upper eyelid position, measured from standardised facial photographs. Secondary outcomes included ocular motility, retinal structure, visual acuity, and patient-reported outcomes. Adherence and safety were assessed throughout. Results Five participants (mean age 13.3 ± 2.0 years) were enrolled; four completed 18-month follow-up. Underlying diagnoses included Kearns–Sayre syndrome, m·3243A > G-related disease, and TAMM41-associated mitochondrial disease. Adherence, where recorded, was high (96–100%). There was no clinically meaningful improvement in ptosis following initiation of red light therapy. Similarly, no significant changes were observed in ocular motility, retinal imaging, visual acuity, or quality-of-life measures. The intervention was well tolerated, with no treatment-related adverse events reported. Participants and caregivers found the treatment acceptable and easy to incorporate into daily routines. Conclusions In this small proof-of-concept study, daily exposure to deep red light was safe and feasible, but did not demonstrate a measurable benefit for ptosis in CYP with primary mitochondrial disease. Lack of efficacy may relate to advanced disease stage, fibrosis of affected muscles, or underlying genetic heterogeneity. Future studies should explore earlier intervention, larger cohorts, and integration with routine care, including home-based outcome assessment. Study registration Clinicaltrials.gov NCT06292182 first posted 27 February 2024.