A descriptive study of early eyelid morphogenesis in a large-scale human embryo collection

Human eyelid development begins during the embryonic period. Although the general outline of early eyelid development has been described, many structures and developmental phenomena remain insufficiently investigated or controversial mainly due to the scarcity of human fetal specimens. The purpose of this study is to clarify these unresolved issues and to determine the precise developmental timing of each eyelid structure.

Fifty-six embryos (Carnegie stage (CS) 18-23) and six fetuses (early 9th week of development) from the Kyoto Collection were included in this study. The anatomical structures of the eyelid were observed using serial histological sections and external photographs, and the findings were described according to each developmental stage.

The medial and lateral canthi formed between CS19 and 21. Mesenchymal condensations corresponding to the prospective upper and lower eyelid retractor regions were first observed at CS18 and acquired a sheet-like configuration by the 9th week of development. Mesenchymal condensation at the future location of the medial palpebral ligament was first observed at CS20. The orbicularis oculi muscle primordium emerged at the 9th week. Eyelid fusion initiated on the nasal side at CS22. It then progressed from both the nasal and temporal sides towards the center, until completion at the 9th week. The lacrimal canaliculi first appeared at CS19.

Using the rich specimens of the Kyoto collection, we newly identified the developmental timing of the prospective lower eyelid retractor complex and medial palpebral ligament regions, as well as the initiation of eyelid fusion on the nasal side. Furthermore, we established a detailed timeline of early human eyelid morphogenesis. Our findings may guide future research on human eyelid development, anatomy, and the mechanisms underlying congenital eyelid disorders.