Talk:Paper - The development of the eyelids 1
PEARSON AA. References
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The development of the eyelids
Part I. External features
ANTHONY A. PEARSON
Department of Anatomy, School of Medicine, University of Oregon Health Sciences Center, Portland, Oregon 97201
J. Anat. (1980), 130, 1, pp. 33-42
With 16 figures
(Accepted 17 January 1979)
Many anatomical features of the developing eyelids are superﬁcial and can be seen in photographs of . human embryos and fetuses. These are recorded in the present paper (Part 1). There are many intrinsic structures, however, which lie beneath the surface of the skin and require microscopic study: Part 2 will be a histological study of the development of these intrinsic structures and the relation of the eyelids to the orbit. Often structures in the adult can be better understood through studies of their developmental history: this is true of the eye and the orbit. Embryonic and fetal structures should not necessarily be regarded as miniature models of adult organs, although this is sometimes the case.
MATERIALS AND METHODS
This study is based on observations of human embryos and fetuses over a period of many years. In addition to the material in our laboratory, it includes observations on the collections of human embryos and fetuses in the Carnegie Laboratories of Embryology at the University of California at Davis. In 1967 this author studied the collection of human embryos of Dr Hideo Nishimura, Professor of Anatomy, Faculty of Medicine, Kyoto University, in Japan. Many of the photographs of embryos used in this study were obtained through the courtesy of Professor Nishimura. The embryos were classiﬁed according to a timetable of human develop- ment known as the Carnegie system or ‘ Streeter’s horizons ’ (Streeter, 1951; O’Rahilly, 1966, 1975, 1978; and Nishimura, Semba, Tanimura & Tanaka, 1977). The staging of human embryos covers the ﬁrst two months (8 weeks) of prenatal life and is divisible into 23 stages or ‘ horizons ’. This paper is concerned with the development of the eyelids during the ﬁrst 8 weeks of prenatal life. It should be mentioned that the ages given for these embryos are approximate only.
Stage 9 (16-25 mm; lg-3 pairs of somites; 20 days i 1). With the formation of the neural _ folds in this stage the central nervous system has begun to differentiate. The neural groove is deep and the regions of the spinal cord, rhombencephalon, mesencephalon and prosencephalon can be distinguished (O’Rahilly & Gardner, 1971). = R A
Stage 10 (2-35 mm; 4-12 pairs of somites; 22 days 3: 1). The optic primordium and sulcus have developed in the prosencephalic neural folds and the ridge of the
Eyelid development 35
future optic chiasma has formed. These are early signs related to eye development. The otic placode has begun to develop as a small thickening of the surface ectoderm lateral to the hindbrain (Bartelmez & Blount, 1954; O’Rahilly, 1966). ,
Stage 11 (25-46 mm; 13-20 pairs of somites; 24 days :1). The rostral neuropore has closed. The optic vesicle has begun to form from the optic sulcus. The otic pit has formed (Streeter, 1951; O’Rahilly & Gardner, 1971).
Stage 12 (3-5 mm; 21-29 pairs of somites; 26 days :1). The optic vesicle lies close to the surface ectoderm (O’Rahilly, 1966).
Stage 13 (4-6 mm; 30 + pairs of somites; 28 days i 1). The lens disc has developed as an area of thickened surface ectoderm overlying the optic vesicle (O’Rahilly, 1966). This area of thickened ectoderm is not clearly shown in Figure 1, but its position can be judged from the location of the lens pit in Figure 2. In embryos of this stage, the frontal process is prominent, the nasal placode has begun to develop and the ﬁrst four pharyngeal arches are well developed. 4
Stage 14 (5-7 mm; 32 days i-1). The lens placode is now indented by the lens pit (Fig. 2). After ﬁxation and treatment in certain ﬂuids, embryos of this age become more transparent (Fig. 3). The position of the optic cup deep to the lens disc can be readily seen. The large ganglion of the trigeminal nerve is seen in the area dorsal to the maxillary process, which is developing as an outgrowth of the ﬁrst (mandibular) pharyngeal arch. The otic vesicle can be seen dorsal to the second pharyngeal groove. The acousticofacial ganglion is located" just rostral to the otic vesicle. In embryos of this stage the lens disc shows various degrees of indentation and may be cup-shaped (Streeter, 1951;" O’Rahilly, 1966). Note the position of the heart, the limb buds and the tail in Figures 2 and 3.
Stage. .15 (7-9 mm; 33 days :1). The lens pit is now closed (Fig. 4), but the lens vesicle is still close to the surface ectoderm. The optic cup and lens vesicle appear to press against the surface ectoderm, causing a slight elevation in the region of the eye. This reveals something of the contour of the developing eye structures which lie beneath the surface. The developing eye lies superior to the maxillary
process and posterior to the olfactoryeplacode. The olfactory placodes have begun .
to sink into the mesoderm to form the olfactory pits. The surface epithelium over
. the closed lens vesicle constitutes the anterior layer of the future cornea (O’Rahilly, 1966). S .
Stage 16 (8-11 mm; 37 days :1). In this stage the olfactory pits have deepened, resulting in the formation of the lateral and medial nasal processes. The relations of these processes to the maxillary process are clearly shown (Fig. 5). Auricular
Fig. 1. Lateral view of the head region of a 5-4 mm human embryo, Stage 13. Four pharyngeal arches and grooves are clearly shown. Position of lens disc can be estimated from position of lens pit in Fig. 2. '
‘ Fig. 2. Lateral view (slightly oblique) of the head region of a 6-4 mm human embryo, Stage 14. Prominent swellings indicate the parts of the developing brain. The lens disc is now indented and the lens pit is visible. ~
Fig. 3. Lateral view of a 6-4 mm human embryo, stage 14. The superﬁcial tissues are fairly transparent and certain structures can be seen beneath the surface. Note the following: optic cup, lens, pharyngeal arches and grooves, trigeminal ganglion,VII-VIH nerve ganglion and otocyst. The heart, limb buds and tail are prominent features.
Fig. 4. Lateral view (slightly oblique) of the head region of a 7-1 mm human embryo, Stage 15.‘ Note the depression of the ectodenn fonning the olfactory placode. The maxillary process has begun to develop. The contours of the optic cup and lens vesicle can be recognized through the surface ectoderm. The lens pit is closed.
‘ hillocks have begun to form on the mandibular and hyoid (ﬁrst and second
pharyngeal) arches. The contour of the optic cup makes a visible impression on the surface ectoderm. The ﬁrst indication of the development of the eyelids is the formation of a small depression above the eye and another below it. A small ridge or elevation extends rostrally and another caudally from the eye. These are bounded above and below by the slight depressions mentioned. The groove below the eye is bounded by the superior margin of the maxillary process. The lower jaw has begun to be established. The mouth, nose and other facial structures are in the early stages of development. The regions of the telencephalon, mesencephalon, metencephalon, and myelencephalon can be recognized.
Stage 17 (11-14 mm; 41 days i 1). The head is now relatively large, and parts of the face can be recognized (Figs. 6, 7). The groove below the eye is more distinct and it is continuous with the nasolacrimal groove which lies between the maxillary process and the lateral nasal process. The groove above the eye is present, but it is less distinct. The pigment in the optic cup is visible through the surface ectoderm, revealing the shape of the developing eye. Although the eyes are still laterally placed, they have begun to take a more anterior position. The parts of the upper and lower jaws are more distinct and have begun to ﬁt into place. The auricular hillocks which form the external ear are visible on the sides of the hyomandibular groove which will become the external auditory meatus. The lower eyelid fold has begun to form. The thin roof of the fourth ventricle is visible.
Stage 18 (13-17 mm; 44 days i 1). The nose has taken on a more deﬁnite shape (Figs. 8, 9). The relations of the nasolacrimal groove to the eye and the nose are still apparent. The eyes have shifted to a more anterior position. The upper and lower jaws show further signs of development. The groove above and the groove below the eyes are deeper; however, they have not joined laterally or medially (Fig. 9). As a result, the bridge of tissue extends from the medial side of the eye to the lateral nasal process. Note a similar bridge of tissue on the lateral side. As the lower groove deepens, the lower lid is formed by a fold of tissue from the maxillary process (W hitnall, 1932). The grooves related to the eye will be referred to as the lid, or conjunctiva], grooves. The upper eyelid fold is also now distinct (Mann, 1964). The developing external car has taken a more lateral and posterior position. A small notch or depression is sometimes present near the middle of the upper lid fold (Figs. 8, 9).
Stage 19 (16-18 mm; 48 days :1). The upper and the lower lid grooves have deepened and the eyelid folds are more distinct (Figs. 10, 11). The upper and the lower jaws show further signs of development, and the nose and the lips are taking
Fig. 5. Lateral view (slightly oblique) of the head region of a 8-2 mm human embryo. Stage 16. Note the groove above the eye. The groove below the eye is bounded by the maxillary process and the lateral nasal process. The upper and the lower jaws are beginning to take form.
Fig. 6. Front view of the headof 3. 112 mm human embryo, Stage 17. Note the relations of the medial and lateral nasal processes to the maxillary process. Also note formation of the lower jaw, the hyomandibular (ﬁrst pharyngeal) groove, and the position of the eye.
Fig. 7. Lateral view of thehead region of the same human embryo shown in Fig. 6, 11-2 mm, Stage 17. The groove below the eye is continuous with the nasolacrimal groove. The maxillary process, the mandibular arch and the hyomandibular groove are distinct. Note the thin roof of the hindbrain.
Fig. 8. Front view of the head region of a 14 mm human embryo, Stage 18. Note the position of the eyes and the ears, and the shape of the nose and jaws. The upper and the lower eyelid folds are now distinct.
shape. The nasolacrimal groove has disappeared, or is less distinct. The palpebral
ﬁssure is still wide, but is becoming more almond-shaped. The lid grooves are in the process of encircling the lateral aspect of the eye where they join. The bridge of tissue on the medial side of the eye is still prominent. The notch in the upper lid fold is sometimes present (Figs. 10, 11). The upper and the lower eyelids now meet at the lateral canthus.
Stage 20 (18-22 mm; 51 days :1). The nose, mouth and chin are further developed. The ears are more lateral and posterior in position (Fig. 12). The eyes are directed more anteriorly. The upper and lower lids meet laterally and medially at acute angles, and the outer and inner canthi are established. The lid grooves forming the margins of the conjunctivum now extend around the eye, completing the limits of the conjunctival sac. Pigment in the eye is clearly visible and the outline of the pupil can be recognized. Although the eyelids partly cover the eye, the palpebral ﬁssure is still wide. The notch sometimes present in the upper lid is shown in Figure 12.
Stage 21 (22-24 mm; 52 days :1). The almond-shaped lid groove is deeper, and the conjunctival sac is more completely established (Fig. 13). The lateral and the medial angles of the palpebral ﬁssure are more acute. The bridge of tissue on the medial, and the one on the lateral side of the eye are partially covered by the eyelids. The palpebral ﬁssure becomes narrower as the eyelids cover more of the eye. The nose is still ﬂattened: however, the mouth, lips and chin are more deﬁnitely formed. The superﬁcial vascular head plexus has spread upwards and now forms an irregular line a little more than half the distance from the eye-ear level to the vertex of the head (Streeter, 1951). The notch or depression in the upper lid fold is barely visible in some embryos of this stage, and is not present in most (Fig. 13).
Stage 22 (23-28 mm; 54 days i 1). As the eyelids continue to develop they thicken and cover more of the eyeball (Fig. 14). The eyes are now directed more anteriorly and, with the development of the chin, the ears are pushed into a more lateral and posterior position. The superﬁcial vascular plexus now lies about three- fourths of the way above the eye-ear level and is near the vertex of the head (Streeter, 1951). The superﬁcial aspects of the eye closely resemble those of stage 21 (Fig. 13).
Stage 23 (27-31 mm; 57 days i 1). This stage (Fig. 15) represents the end of the embryonic period and the face is beginning to look human. The nose is still ﬂat, but is beginning to develop a point. The jaws are well established, and the tragus, the antitragus and the helix of the external ear can be identiﬁed. The eyelids are
Fig. 9. Lateral view of the head of the same embryo shown in Fig. 8 (14 mm, stage 18). Note the upper and the lower lid grooves and the bridge of tissue connecting the lateral and the medial sides of the eye with the adjacent tissues. This is an unusual view of the proﬁle of the nose, mouth and ear.
Fig. 10. Front view of the head region of a 16-5 mm human embryo, Stage 19. Note the position of the eyes and the ears, and the shape of the nose and the mouth- Observe the lid grooves and the eyelid folds.
Fig. 11. Lateral view (slightly oblique) of the same embryo shown in Fig. 10, 16-5 mm, Stage .19. The lid grooves extend around the lateral aspect of the eye, and meet, forming the lateral canthus.
Fig. 12. Front view of the head of a 18-4 mm human embryo, Stage 20. Note that the palpebral ﬁssure is more almond-shaped, and that the lid groove now completely surrounds the eye. The lateral and the medial angles (canthi) of the palpebral ﬁssure are now established.
further developed and cover more of the anterior surface of the eye.‘ The process of fusion of the lids appears to result from a gradual narrowing of the palpebral ﬁssure, which is complete by the end of stage 23.
The fetal period is the remaining part of prenatal life. It has not been staged.‘ Closure of the eyelids is complete at about the 37 mm stage (Mann, 1964). When the margins of the lids come together, the superﬁcial layers of the ectoderm meet and a continuous layer of surface ectoderm is formed. The eyelids remain closed until the latter part of fetal life. The closed eyelids of a fetus are shown in Figure 16.
The sequence of developmental events and their timing are important in the study of human embryology and so it is necessary to employ a system of staging. It has been shown that neither the length of the embryo nor the estimated age is suﬂicient to establish a stage: the stage number must be related to the developmental status of the entire body. The human eye is one of the few organs where morph- ological stages have been used in a developmental study (Streeter, 1951; O’Rahi1ly, 1966, 1975, 1978). -
Some authors (Duke-Elder & Cook, 1963; Warwick, 197 6) have stated that the eyelids are formed by a circular fold which develops around the eye, and that the palpebral ﬁssure at ﬁrst is round and without angles. The upper lid is sometimes described as being formed from two parts, medial and lateral, and that occasionally in an adult a notch or coloboma may result from their imperfect union (Whitnall, 1932; Duke-Elder & Cook, 1963). In the present study a small notch or depression in the upper lid fold was found in some embryos in Stages 18-20 (Figs. 8-12). This author would like to investigate the matter further before commenting on the signiﬁcance of the notch. Investigators do not agree about the details of the process of fusion of the eyelids: some believe that fusion takes place from the ends of the palpebral ﬁssure and continues toward the middle (Whitnall, 1932); others state that the lids ﬁrst meet at the outer canthus (Corner & Smelser, 1950), others at the inner canthus (Mann, 1964; Pearson & Weleber, 1975), and that closure is complete during Stage 23.
My recent observations on a large series of photographs of human embryos and fetuses indicate that the upper and lower eyelids ﬁrst meet at the lateral end of the palpebral ﬁssure, establishing the outer canthus in Stage 19 (Fig. 11). It is more oval and less acute at this stage than the inner canthus, which is established a few days later in Stage 20 (Fig. 12). From this point on it is somewhat academic to debate whether or not fusion is taking place more rapidly in a medial than a lateral direction. The closure usually takes place during the last few days of the embryonic period, i.e. in Stage 23 (Fig. 15).
Fig. 13. Lateral view of the head of a 23 mm human embryo, Stage 21. The lid grooves are deeper and the eyelids cover more of the eye. Note the superﬁcial vascular plexus.
Fig. 14. Lateral view (slightly oblique) of the head of a 25 mm human embryo, Stage 22. The angles of the palpebral ﬁssure become more acute as the eyelids cover more of the eye. The position of the superﬁcial vascular plexus is slightly higher, indicating that this embryo is slightly older than stage 21. 2
Fig. 15. Lateral view (slightly oblique) of the head of a 28 mm human embryo, Stage 23. Note that the palpebral ﬁssure is narrower. 2
Fig. 16. Lateral view of a 45 mm human fetus (about 10 weeks). The eyelids are closed.
Soon after the fusion of the eyelids the lacrimal caruncle develops from the margin of the lower lid as a result of a portion being cut off by the developing inferior lacrimal canaliculus (Whitnall, 1932). At about the time that the lids are closing the plica sernilunaris is developing as a crescentic membranous fold from the conjunctiva along the medial aspect of the eye (Mann, 1964).
The sequence of developmental events leading to the formation of the eyelids is described in staged human embryos. By the end of the fourth week the optic vesicle lies close to the surface ectoderm. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode (Stage 13). A few days later (about 32 days, Stage 14) the lens placode is indented by the lens pit. A day or two later (about 33 days, Stage 15) the lens pit is closed: however, the lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface. Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it (Stage 16, 37 days). As these grooves deepen, in Stages 17-19, eyelid folds develop, ﬁrst below, and then above, the eye. In Stages 19-22 the eyelid folds develop into the eyelids and cover more of the eye as the palpebral ﬁssure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19.. The inner canthus is established a few days later in Stage 20. Closure of the eyelids is complete in Stage 23.
This study was supported by U.S.P.H.S. Research Grant EYO2275 from the National Eye Institute. It was made possible by the courtesy and generosity of Professor H. Nishimura, who lent me all the photographs illustrated except Figs. 3 and 16.
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