Embryologic and Fetal Development of the Human Eyelid

Abstract

Purpose: To review the recent data about eyelid morphogenesis, and outline a timeline for eyelid development from the very early stages during embryonic life till final maturation of the eyelid late in fetal life.

Methods: The authors extensively review major studies detailing human embryologic and fetal eyelid morphogenesis. These studies span almost a century and include some more recent cadaver studies. Numerous studies in the murine model have helped to better understand the molecular signals that govern eyelid embryogenesis. The authors summarize the current findings in molecular biology, and highlight the most significant studies in mice regarding the multiple and interacting signaling pathways involved in regulating normal eyelid morphogenesis.

Results: Eyelid morphogenesis involves a succession of subtle yet strictly regulated morphogenetic episodes of tissue folding, proliferation, contraction, and even migration, which may occur simultaneously or in succession.

Conclusions: Understanding the extraordinary process of building eyelid tissue in embryonic life, and deciphering its underlying signaling machinery has far reaching clinical implications beyond understanding the developmental abnormalities involving the eyelids, and may pave the way for achieving scar-reducing therapies in adult mammalian wounds, or control the spread of malignancies.

FIG. 1.

The process of eyelid fusion. A, At around week 8, the flattened periderm cells (arrowhead) undergo a morphogenetic and proliferative change into rounded or cuboidal periderm cells. B, The leading edge of these proliferating cells helps make contact with the advancing edge of the opposing eyelid periderm cells until a connection is established. C, When a connection is established between both sides, these periderm cells flatten again and form a continuous sheet ultimately covering the cornea. D, Only the periderm and epidermal layers are involved in eyelid fusion while eyelid mesenchyme (*) remains distinct (Modified with permission from Yu et al.).

FIG. 2.

Maturation of the eyelids during the fetal period. A, Week 9 (40 ± 2 mm). The development of eyelid structures begins in the 9th week immediately following eyelid fusion with mesenchymal cell condensations and an occasional ingrowth of surface epithelium into the underlying mesenchyme, which together contribute to the formation of some eyelid structures. The first to appear is the orbital part of the orbicularis oculi muscle. B, By week 14 (121 ± 11 mm). The eyelid is now clearly divided into separate layers. Rudimentary eyelashes, sebaceous, and sweat glands (*) could be seen near the eyelid margin, and a primordial tarsal plate has formed (arrow). C, Week 20 (195 ± 15 mm). Although the eyelids are still visibly fused, separation has already started anteriorly (*) and is visible in the middle at a microscopic level. Meibomian gland branching is first observed and the tarsal plate has lengthened significantly. The orbicularis oculi muscle looks more fully developed. Nearly mature eyelash follicles about to pierce the eyelid margin are also evident. D, Week 32 (301 ± 33 mm). The eyelid has taken its nearly fully developed appearance. Meibomian glands increase in length and are present in two-thirds of the length of the tarsal plate. The eyelids are fully separated by now but the eyes are still visibly closed. E, Full term. Final appearance of the eyelids at birth, which is not dissimilar from the adult counterpart. OO, orbicularis oculi muscle; MG, Meibomian glands; TP, tarsal plate.