Lockley · The Journal of clinical endocrinology and metabolism 1997 · cross-sectional comparative study · n=49

Relationship between melatonin rhythms and visual loss in the blind.

Cited 271 times in the scientific literature.

Level 4 - case-series / case-control

Cross-sectional comparative observational study

PubMed 9360538 · doi:10.1210/jcem.82.11.4355 · record verified 2026-08-30

What was done

Melatonin circadian rhythms were evaluated in 49 registered blind individuals with various etiologies of visual loss, grouped by visual capacity: light perception or better (LP; n = 19) versus no perception of light (NPL; n = 30). Participants collected urine every 4 hours during the day and every 8 hours overnight over 48-hour blocks at weekly intervals for 3 to 5 weeks to measure the urinary melatonin metabolite 6-sulfatoxymelatonin (aMT6s). Rhythm entrainment, period length, acrophase, amplitude, and 24-hour total excretion were determined.

What was found

In the LP group, 14 of 19 individuals displayed normally entrained aMT6s rhythms (mean acrophase range: 2.4-6.2 h), 4 were abnormally entrained, and 1 was unclassified. In the NPL group, 23 of 30 had abnormal rhythms, comprising 17 free-running individuals (period range: 24.13-24.79 h), 5 abnormally entrained individuals (acrophase range: 7.2-20.6 h), and 1 unclassified individual; abnormal rhythms were more frequent in uni- and bilaterally enucleated subjects. Mean 24-hour aMT6s output did not differ significantly between LP (12.7 +/- 7.5 micrograms/24 h) and NPL (9.4 +/- 6.4 micrograms/24 h) groups, nor did mean amplitude (0.6 +/- 0.4 micrograms/h vs. 0.5 +/- 0.3 micrograms/h).

Why it matters

This study shows that ocular light reception is necessary for entraining human circadian rhythms to the 24-hour day, with complete loss of light perception commonly resulting in non-24-hour free-running melatonin patterns despite intact total melatonin production.

Limits

The sample size is relatively small (n = 49) with heterogeneous causes of visual loss. The study relied on intermittent outpatient urinary metabolite sampling rather than continuous laboratory or blood-level monitoring, and non-photic zeitgebers (such as strict sleep routines or social cues) were not controlled.

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