Ординатура / Офтальмология / Английские материалы / Basic Sciences in Ophthalmology_Velayutham_2009
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cornea curvature starts increasing. If this fails, cornea plana results. Inheritance is autosomal dominant or recessive.
Oval cornea is seen in Turner’s syndrome, Rieger’s anomaly and along with microphthalmos.
Keratectasia in which the cornea is ectatic and opaque is due to intrauterine infection or due to failure of mesenchyme to migrate and develop the cornea.
Posterior keratoconus is a condition where there is a localized diffuse thinning of the central or paracentral cornea on the posterior aspect with an opacity in that area. Unlike Peter’s anomaly the Descemet’s membrane and endothelium will be present in the defective area. Vision is reasonably good as the anterior surface is normal.
Congenital leucomas of any shape and size can occur but they are not so common. This may be associated with other anterior segment anomalies, which were called mesodermal dysgenesis. But these are called neurocristopathies as the structures, which develop from neural crest cells are affected in this condition. Congenital rubella and syphilis also can cause corneal opacities. Multilple macular opacities are sometimes seen bilaterally in some cases. It may also be part of congenital glaucoma and mucopolysaccharidosis.
In arcus juvenilis an opacity similar to arcus senilis is seen. This may be present at birth or develop a little later.
Dermoids: Can be found in the cornea, conjunctiva or orbit. These are choristomas and are due to epidermal and connective tissues being included in between the two sides of a cleft. The dermoid will have many types of tissues like hair follicle, sebaceous glands, nerve fibers, fat and or glandular tissue.
Dermolipomas consist of fat and fibrous tissue and are seen in the fornix at the superotemporal quadrant.
Chromosomal anomalies with corneal abnormalities:
Trisomy 21 |
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Keratoconus |
Trisomy 17,18 |
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Anterior corneal opacities |
Abnormal Ch 18 |
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Posterior keratoconus, microcornea, opacities, |
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Peter’s anomaly, oval cornea, other neuro cristo- |
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pathies |
Trisomy13 |
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Poorly defined cornea with leucoma and sclera- |
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lization |
Turner’s XO |
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Blue sclera, oval cornea and corneal opacity. |
Angle anomalies. These develop from failure of cell differentiation, incomplte migration of secondary mesenchyme, or due to defective regression of mesenchymal cells present in the space between the developing endothelium and iris. Depending up on the degree of defect it ranges from simple prominent Schwalbe’s line which is present in 15% of normal people to gross anomalies in the angle. If insertion of iris processes anteriorly is included along with prominent Schwalbe’s it is called Axenfeld’s anomaly. If glaucoma is also present, it is called Axenfeld’s syndrome.
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If iris strands and hypoplasia of iris stroma are also present it is called Rieger’s anomaly. In Rieger’s syndrome non-ocular defects like macular hypoplasia with a broad flat root of nose, small teeth or even absence of teeth, deafness, mental retardation and osteogenesis imperfecta will be present. These signs may be seen in syndromes like Marfan’s, Down’s and Ehler Danlos.
If central corneal opacity is added to this it is called Peter’s anomaly the inheritance pattern of which is autosomal dominant. In some cases of Peter’s anomaly the lens may be cataractous. In such cases other ocular anomalies like aniridia, sclero cornea, microphthalmos with choroidal coloboma can be present. Systemically trisomy 13 and 15, congenital heart defects, genitourinary disorders, mental retardation, cleft lip and palate and other skeletal abnormalities may also be associated with this condition.
Congenital peripheral anterior synechiae and posterior keratoconus is also part of this type of anomaly. In posterior keatoconus as the anterior curvature is normal the vision is not affected.
Abnormal differentiation of mesenchyme could lead to congenital hereditary endothelial dystrophy, congenital hereditary stromal dystrophy, posterior polymorphous dystrophy, sclero cornea and cornea guttata.
Iris
Anisocoria of 0.5-2mm can occur in normal people. Polycoria (many pupils), ectopia (displaced pupil) and corectopia (deformed pupil) also are seen. Cysts can occur congenitally in the iris.
In aniridia though it appears as if the whole iris is absent some rudimentary tissue is present in the periphery. It can be inherited as an autosomal dominant or recessive trait. When it is associated with Wilm’s tumor deletion of part of short arm is seen.
Colobomata
Coloboma literally means mutilation. When a part of a structure of the eye is missing it is called coloboma of that part. When this is due to defective closure of the embryonic fissure it is called typical coloboma. This anomaly will occur when the development of the fetus is affected during the fourth and fifth week of gestation. This is the time when the optic vesicle invaginates and fusion of the fissure occurs. Normally the cleft starts closing in the center and then proceeds both anteriorly and posteriorly. Depending on at what stage the defect starts the coloboma will be partial or complete.
Colobomata may be due to primary defect in the ectodermal development.
Inheritance: Autosomal dominant.
Coloboma of retina and choroid: A complete coloboma involves the iris, lens, choroid and optic disc. It is bilateral in 60% of cases. Instead of a total coloboma
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multiple defects may be seen along the embryonic fissure. In these cases the sclera will be thin and sometimes ectatic. The choroid is absent except for a few large vessels. Though the macula is normal vision will be affected and nystagmus may be present. When coloboma occurs in the ciliary body the zonules will be defective causing coloboma of the lens.
Coloboma of the Iris: is usually a triangular or tear drop-shaped defect in the lower nasal quadrant of the iris. The broad base is usually towards the pupil but the shape may vary. This coloboma is either due to defective closure of the embryonic fissure in the anterior part or persistence of the vessels in the tunica vasculosa lentis. In the later case, the coloboma can occur in any clock hour. The vessel anastomosing with the hyaloid artery at the level of the embryonic fissure is larger. Hence colobomas are more common at this site. If many vessels persist many colobomas result and if all the vessels persist aniridia ensues.
Sclera: Translucent sclera makes the uveal tissue more visible giving it a bluish appearance. Hence it is called blue sclera. Staphyloma can occur congenitally in the peripapillary region.
Uveal Tract
Iris: Hypoplasia of iris is very common. This may be limited to one quadrant or either the mesodermal or ectodermal parts of the iris. In pseudopolycoria multiple holes are seen in the iris. In iridodiastasis the defect is seen in the ciliary margin. This resembles an iridodialysis but the pupil will be round in shape.
Optic Nerve
Bilateral hypoplasia of the optic nerve is usually associated with other anomalies like microphthalmos or absent septum pellucidum. EG de Morsier syndrome. Unilateral hypoplasia is sometimes seen in otherwise normal persons. Colobomas may be confined to optic nerve head alone.
Optic nerve pit is a deep circular depression in the nerve head located more commonly in the inferior temporal quadrant. The cause for the formation of the pit is the presence of a small pouch of retinal tissue between the nerve and the sclera. There will be a defect in the lamina cribrosa. It is thought that there is a continuity between the subretinal space and the subdural space. Through this space cerebrospinal fluid can enter the subretinal space causing a condition resembling central serous retinopathy. An arcuate scotoma will be present in these cases.
Hyaloid vessels may be present in the vitreous. Depending on when the regression has stopped the extent of remaining vessel will vary. If the posterior end is persistent it forms a elevation called Bergmeister’s papilla over the disk.
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If the anterior end persists, it will be attached to the back of the lens slightly nasal to the center and is called Mittendorf’s dot.
Very rarely the whole empty vessel will be hanging between the disc and the lens.
In persistant hyperplastic primary vitreous or persistant fetal vasculature there is a fibrovascular sheath behind the lens. This contracts and pulls the ciliary body causing elongation of the ciliary processes which is pathognomonic for this condition. The vessels may enter the lens and even cause hemorrhage in the lens. As the development of the eye is affected there is microphthalmos, retinal dysplasia and amblyopia. The anterior chamber will be shallow with a clear or cataractous lens. Fortunately, this condition is uniocular.
Defects in the Eyelids
Coloboma of the eyelids where there is a defect in the eyelid margin is due to defective fusion of the facial processes.
The skin over the eyelids and at times the sclera and uveal tract are heavily pigmented on one side alone. It is called nevus of Ota. As primary open angle glaucoma is more common in these cases they must be followed up for the same.
Nevi may be present as isolated lesions on the eyelids, conjunctiva, caruncle, iris and choroid.
In the orbit dermoids which are choristomas can occur. It is usually found in the superotemporal quadrant. Though they are present from birth they become evident in the second or third decade. These tumors produce a defect in the orbital wall. Sclerosis of the bone at the tumor margin will be present.
At birth the eye is only about 12.5 to 16 mm in size. This makes the eye hypermetropic. The cornea is 10 mm in diameter, which makes it very large compared to the anteroposterior diameter of the eye. It is also more curved in the periphery the reverse of what is seen in an adults eye. The medial rectus is closer to the cornea.
Pigmentation of the iris continues after birth. In infants the pupil will be constricted and will not dilate properly as the dilator muscle fibers are not well developed. In addition to this the anterior chamber will also be very narrow. This makes it difficult to do surgeries in congenital cataract. The ciliary processes also will not be fully developed at birth. The ciliary muscle will be very short which makes the retina lie very close to it. Hence any incision through the parsplana must be very carefully made.
During the first three years of life the eye grows rapidly. It continues at a slower rate till puberty following which, there is another spurt of growth. Myelination of the optic nerve is completed by the third week after birth.
As age advances the cornea is flattened in the vertical meridian, giving rise to astigmatism against the rule. Deposition of lipids in the cornea causes arcus
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senilis. Lipids in the sclera causes thickening and yellowish discoloration. The pupil becomes miotic and the sphincter pupillae becomes rigid. The pigment epithelium atrophies especially around the disc.
CHRONOLOGY OF DEVELOPMENT
Period |
Organogenesis |
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3rd week |
Formation of optic vesicle from optic pit. Lens plate |
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forms in the surface ectoderm |
4th week |
Invagination of optic vesicle to form optic cup formation of |
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lens pit and towards the end of 4th week of lens vesicle. |
5th week |
Fetal fissure starts closing |
6th week |
Closure of fetal fissure |
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Separation of lens from the surface. |
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Formation of primary lens fibers |
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Differentiation of various layers of retina |
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Appearance of tunica vasculosa lentis |
Neofetal period: |
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12th week |
Formation of secondary lens fibers, lid folds and ectodermal |
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layers of iris. |
Fetal period: |
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16th week |
Development of central retinal vessel, ciliary body, ciliary, |
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sphincter and dilator muscles |
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Sclera and outer layer of choroid. |
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Regression of vascular capsule of lens |
28th week |
Regression of pupillary membrane |
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myelination of the optic nerve starts |
9 months |
Hyaloid artery disappears and medullation reaches lamina |
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cribrosa. |
After birth: |
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3 weeks |
Myelination is complete, lens becomes flatter but continues |
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to grow throughout life. Hypermetropia |
1 month |
Fovea is fully-developed. Location same as adults. |
6 months |
macula is fully developed |
2-4 years |
Angle of anterior chamber reaches adult size. The anterior |
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part of the orbit grows more than the posterior |
Adult life |
Eyeball is three times that found at birth. |
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12 General
Biochemistry of the Eye
The various types of tissues that form the eye are specifically or specially designed for transmission of light and conversion of light energy into cellular signals that are transmitted through second messengers like ion channels, G protein, tyrosine kinases etc. Like the cells in any other organ, the ocular cells also have basic structural organelles such as plasma membrane, nucleus, cytoplasm with endoplasmic reticulum, golgi apparatus, mitochondria and intracellular matrix. Intracellular matrix has filaments of 3 types as microfilaments, intermediate filaments and cytoskeletal fibres. The cells lie in the extracellular matrix that form the structural framework with proteins such as collagen and proteoglycans (glycosaminoglycans bound to core proteins).All these structures are designed for the specific function of light transmission. The metabolism in these ocular cells also occur similar to the other cells.
STRUCTURAL PROTEINS
Collagen is a protein of great structural importance to the eye. About 80-90% of the bulk of the eye contains collagen. It is an extracellular, insoluble molecular complex. It acts as a supporting medium to hold cells and to maintain the tissue structure. It may be fibrous or non-fibrous. So far, 19 types of collagen have been identified.All types of collagen are protein complexes of 3 polypeptides wound around each other in a helical structure like a rope. Each polypeptide chain has á helical structure and so collagen is a triple helix (Fig. 12.1). The polypeptides are rich in proline and lysine. These amino acids are post translationally hydroxylated by hydroxylase enzymes to form hydroxyproline and hydroxylysine which are necessary for cross linking and hydrogen bonding (Fig. 12.2). In the polypeptide chain every third amino acid is glycine. The small size glycine is useful to maintain the helical structure of the collagen. The 3 chains associate themselves by hydrophobic interactions and are linked by disulfide bonds at their ‘C’ terminal region enabling them to twist and form a stable triple helix of procollagen (Fig. 12.3). The stability is enhanced by interchain hydrogen bonding at the hydroxyl groups. The amino acid sequence of these polypeptide chains may be similar and it is called homopolymeric or dissimilar known as hetero - polymeric, e.g.–Type I collagen is heteropolymeric and Type II is heteropolymeric. The procollagen undergoes hydrolysis of the
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Fig. 12.1
non helical N and C terminal portions (extension peptides) to form the tropocollagen (Fig. 12.4). The tropocollagen comes out of the cell and assembles close to the cell surface. The tropocollagen units associate laterally and staggered lengthwise by hydrophobic interactions and cross linking of lysine and hydroxylysine. 5 such rows of cross linked tropocolllagen units is called microfibril (diameter 10 - 300 nm (Fig. 12.5)). Many such microfibrils make a fibril (Fig. 12.6). Association of several fibrils together is termed fiber (Fig. 12.7). Alternate arrangement of procollagen into nets or spider web structures and polygonal surfaces give rise to the sheet forming, non fibrous collagen.
CELLULAR SYNTHESIS OF COLLAGEN (Figs 12.2 to 12.7)
Collagen types: Those having structural role and non structural role Structural
Fibrillar – Type I, II, III, Vand VII Non fibrilar – Type IV, VI, VIII and X
Non structural
Types IX, XI, XII, XIII, XIV
Fig. 12.2
Fig. 12.3
General Biochemistry of the Eye |
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Fig. 12.4
Fig. 12.5
Fig. 12.6
Fig. 12.7
Fig. 12.2 to 12.7: Cellular synthesis of collagen
STRUCTURAL CARBOHYDRATES
They are sugar oligomers and polymers.
OLIGOMERS
Oligomers are oligosaccharides: They are a class of carbohydrates in which ten or fewer sugars are held together by oxygen bridges. Oligosaccharides are commonly found as covalent appendages to many proteins known as glycoproteins. They are bound to protein by either oxygen bridges (O-linked through serine/ threonine) or nitrogen bridges ( N- linked through asparagine). Some oligosaccharides are also bound to lipids in cell surface membranes.
POLYMERS: (GLYCOSAMINO GLYCANS) - GAG
They are found throughout all bodily tissues including the eye. They exist predominantly in the extracellular matrix that maintains the structure of the organism. They are involved in cushioning, lubricating and attaching the matrix to various kinds of cells. The polymer is made of repeating units of sugar bound to an amino sugar by oxygen bridge. They are also called mucopolysaccharides (MPS) as they were first found in mucous tissues and are