Embryology of the Eyelid
Key Points
Prenatal development in humans is divided into two periods: embryonic and fetal
During the embryonic period, eyelid morphogenesis is a dynamic process involving complex interactions between the developing epidermis and dermis
Intra-epithelial and epithelial-mesenchymal interactions are integral for normal eyelid formation
Surface ectoderm gives rise to the conjunctiva, skin epithelium, hair follicles, Zeis glands, glands of Moll, and meibomian glands
The tarsal plate, levator muscle, orbicularis muscle, orbital septum, and tarsal muscle of Müller develop from the mesenchyme
Mesenchymal contributions to the developing eyelid primarily originate from the cranial neural crest cells
Development of definitive eyelid structures begins following eyelid fusion in the ninth week in the fetal period
Prenatal development in humans is divided into two arbitrary periods: embryonic and fetal.1 The embryonic period begins with fertilization of the egg and ends 8 weeks later. The fetal period begins at week 9 and continues until delivery. During this embryonic period, eyelid morphogenesis is a dynamic process that involves complex interactions between the developing epidermis and dermis.1,2,3 A large number of signaling molecules and pathways coordinate two major tissue interactions during early eyelid development; these are intra-epithelial and epithelial-mesenchymal interactions. Both types of interactions are critical for normal eyelid development.4 In general, the eyelids develop from secondary mesenchyme that is invaded by cranial neural crest cells, as well as from surface ectoderm.5,6,7 The surface ectoderm gives rise to the conjunctiva, epithelium of the skin, hair follicles, Zeis glands, glands of Moll, and meibomian glands. The tarsal plate, levator muscle, orbicularis muscle, orbital septum, and tarsal muscle of Müller develop from the mesenchyme.8,9 Mesenchymal contribution to the developing eyelid primarily originates from cranial neural crest cells. The mesodermal contribution is limited to the endothelium of blood vessels and striated muscles in the eyelids and orbit.7
The Embryonic Stage
At the 31- to 35-day (5-7 mm) embryonic stage, the lens pit starts to invaginate from the surface ectoderm, but there is as yet no indication of an eyelid fold.10 The first indication of the embryonic eyelid occurs around the beginning of week 6 (37-42 days, 8-11 mm stage) where small grooves develop in the surface ectoderm immediately above and below the developing eye. These rapidly deepen to form the eyelid folds.7,10 By the end of week 6 (42-44 days, 11-14 mm stage), the upper eyelid fold is barely visible and is less distinct than the lower eyelid fold,7,10,11 but distinct upper and lower eyelid folds are well defined by week 7 (48-51 days, 16-18 mm stage). At this stage, the upper eyelid starts to assume its dominant role compared with the lower eyelid.12 Both folds are covered by epithelium on their anterior and posterior surfaces.10 Also at this stage, a solid cord of epithelial cells invaginates into the thickened mesenchyme in the medial 1/6th of the eyelid and bifurcates forming the precursors of puncti and canaliculi.11,13,14,15
At the beginning of week 8 (54-56 days, 23-28 mm), there is a persistent gap between the upper and lower eyelid folds, exposing the cornea. The surface ectoderm cells start to migrate toward each other from the rim of both eyelids, beginning the process of eyelid fusion.4,7,16 When a connection is established between both sides, the surface cells flatten again and form a continuous sheet, ultimately covering the cornea (Figures 2.1 and 2.2).
The epidermal layer is involved in eyelid fusion, but the eyelid mesenchyme remains distinct and unfused (Figures 2.3 and 2.4).17 By the end of week 8 (56-60 days, 27-31 mm), the process of eyelid fusion is complete, and this coincides with the conclusion of the embryonic stage and the beginning of the fetal stage.10,11