The wall of the eye globe is composed of the cornea and the sclera. The latter covers the posterior four-fifths of the globe with anterior and posterior openings for the cornea and the optic nerve, respectively.
The cornea is the most anterior part of the globe and is normally optically clear. A healthy overlying tear film is important for the optimal function of the cornea and the esthetic wellness of the ocular surface. The cornea is a complex structure that is responsible for protection and about three-quarters of the optical power of the natural eye with the remainder coming from the crystalline lens. The normal cornea is devoid of blood vessels to insure optimal transmission of light rays.
Oxygen and nutrients are supplied, and metabolic products are eliminated primarily through the tear film anteriorly and aqueous humor posteriorly. The cornea is one of the most densely innervated tissues in the body.
Thus, traumatic corneal abrasions, bacterial keratitis, and bullous keratopathy are associated with severe pain, tearing, and photophobia. The corneal nerve plexuses are supplied by the first division ophthalmic nerve of the fifth cranial nerve trigeminal nerve [ 1 ]. Corneal dystrophies are defined as a group of slowly progressive, usually inherited, bilateral, and symmetric corneal opacifying disorders that might be associated with variable degrees of decreased vision and discomfort.
Typically, they are not linked to environmental or systemic factors. Based on the cellular origin of corneal dystrophy, a modified anatomic classification is proposed consisting of epithelial and subepithelial, epithelial-stromal, stromal, and endothelial dystrophies [ 3 ].
Degenerations generally result from steady deterioration of the tissues that was previously normal with subsequent loss of their functional activity. Corneal degenerations are characterized by the deposition of a specific material, stromal thinning, and vascularization. They are not hereditary and can be unilateral. The cornea may undergo changes associated with ultraviolet light stimulation and oxidative stress that are thought to be responsible for the progression of degenerative processes [ 4 , 5 ].
Corneal ectasia refers to a group of noninflammatory conditions characterized by bilateral loss of corneal biomechanical strength leading to progressive thinning and bulging of the cornea with resultant irregular astigmatism and decreased visual acuity. Examples include keratoconus, post laser-assisted in situ keratomileusis LASIK ectasia, pellucid marginal degeneration, and keratoglobus [ 1 ].
We will start this chapter by describing the basic sciences of the normal human cornea including embryological, anatomical, histologic, and physiological features of the cornea with mentioning selected related functional aspects.
Later, we will discuss the most important corneal dystrophies, degenerations, and ectasia from clinical, histopathologic, and management points of view.
Corneal development and differentiation are the last in the well-organized series of ocular tissue formation. Thus, normal corneal development depends on normal development of the lens and optic cup. The corneal development begins on the 22nd day of gestation as the surface ectoderm, the primordium of the corneal epithelium, and can be identified at the start of the 6th week of intrauterine age [ 8 ].
The neural crest cells come in three distinct waves. The first wave, in the 7th week, migrates between the primitive corneal epithelium and the lens epithelium to form the corneal endothelium. The second wave migrates to the area situated between the future corneal endothelium and the corneal epithelium and gives rise to keratocytes, the cells of the corneal stroma.
The third wave of neural crest cells is located in the primitive anterior chamber to form the iris stroma [ 9 , 10 , 11 , 12 ]. Keratan sulfate is a proteoglycan that is produced by keratocytes and can be demonstrated at the 8th week of gestation.
It is present in keratocytes and endothelial cells but not the epithelial cells [ 13 , 14 , 15 ]. The early corneal epithelium is composed of two layers, apical and basal layers. The outer apical cells are cuboidal without microvilli and are joined together by junctional complexes: zonula occludens and zonula adherens.
They are connected to the basal cell by desmosomes [ 16 ]. The epithelium increases to three cell layers at day postpartum and continues to thicken until reaching the adult thickness of about six layers by the 4th week of life [ 17 ].
The corneal limbus is simply described as the transition zone between the peripheral corneal margin and the anterior sclera.
Its width is approximately 1—1. One of the important characteristics of the limbus is that it contains the corneal stem cells detected in the basal cell layer. The limbus can be defined from histological, pathological, and surgical points of view. The peripheral margin is bordered by the scleral spur. Surgeons divide the limbus into two zones: a central blue zone and a peripheral concentric white zone.
The trabecular meshwork is located under the white zone [ 19 ]. The cornea is the round transparent portion of the eyeball. It is the strongest refractive component of the optical system of the eye.
To maintain its transparency, the normal cornea is avascular, relatively acellular, and relatively dehydrated with extraordinary organization of the stromal collagen lamellae. The diameter of the cornea measures 11—12 mm in horizontal meridian and 10—11 in vertical meridian. This percentage is controlled by an intact epithelium and a normally functioning endothelial pump. The refractive index of the cornea is 1. As previously mentioned, the corneal epithelium is derived from the embryonic surface ectoderm and lies on the outer surface of the cornea.
The epithelium is composed of 5—6 layers of nonkeratinized stratified squamous epithelium overlying a single layer of basal cells. Complete renewal of the epithelial cells occurs in 7—10 days. Three distinct layers of epithelial cells are identified: superficial flattened cells, middle wing cells, and deep basal cells [ 18 ]. The superficial and the wing cells differentiate from the basal cells. They are derived from the corneal limbal stem cells.
Gab junctions serve to provide communication channels between basal cells. A basal lamina that is 50 nm thick, and is composed of type IV collagen, is actively secreted by the basal cells. The cells are attached to the underlying basal lamina via hemidesmosomes. Recurrent epithelial erosions, seen in patients with epithelial basement membrane dystrophy EBMD , are caused by alteration of hemidesmosomes [ 18 ].
On the top of basal cells are 2—3 cell layers of wing cells. They resemble wings in cross section. Wing cells are joined together by zonulae occludentes forming a semipermeable membrane preventing components of the tear film from gaining entry to the corneal stroma.
The superficial layer is composed of 2—3 rows of flattened cells. They shed in the tear film and are replenished by other cells. Microplicae and microvilli are observed on the apical surface of the superficial cells.
Epithelial cells are attached to each other by desmosomes. Topical anesthetic abuse causes a decline in the number of desmosomes with resultant impaired healing [ 20 ]. In contrast to the stroma, the collagen lamellae are smaller and randomly organized [ 18 ]. Weakening of this layer can result in ectatic corneal disorders, such as keratoconus, due to loss of the biomechanical support [ 21 ]. The corneal stroma is derived from the neural crest cells.
Numerically, the central corneal thickness measures about 0. It has corneal stromal collagen lamellae, — lamellae that are arranged parallel to the surface of the cornea. They are predominantly made from type I and type V collagens. Keratan sulfate and dermatan sulfate are the primary proteoglycans of the stroma.
These proteoglycans are located between the lamellae maintaining a constant interlamellar distance, an important factor in eliminating light scatter and, thus, a clear cornea [ 18 ]. There are approximately 2. They synthesize collagen and proteoglycans. Keratocytes are abundant in mitochondria, rough endoplasmic reticulum, and Golgi apparatuses.
The plasma membranes are fenestrated, and they communicate via gab junctions. There is a documented decline in the cell density associated with age [ 18 ]. The anterior part of the stroma is typically drier than the posterior part. This is caused by the drying effect of the atmosphere anteriorly and the wetting effect of the aqueous humor posteriorly.
An enlarged spacing between the lamellae, as in cases of corneal stromal edema from endothelial injury, will result in hazy cornea and decreased visual acuity [ 18 ]. The thickness of DM varies according to the age of the individual. It is continuously secreted by the endothelium through life. Histologically, DM has two layers: an anterior banded layer produced during fetal life and a posterior non-banded layer produced after birth.
It is made of type IV collagen, laminin, and fibronectin [ 18 ]. DM provides support and adhesion to endothelial cells. Under pathologic conditions, it works as a biologic barrier to the phagocytic, toxic, and enzymatic degradation.
The corneal endothelium is the innermost layer of the cornea. As mentioned earlier, the endothelium originates from neural crest cells. The cells cannot be replenished if lost. There is approximately 0. The most common normal cell shape is hexagonal with minimal polymegathism and pleomorphism [ 18 ]. To maintain the corneal clarity, the endothelium works as a barrier and as a metabolic pump. Endothelial cells are linked together by interdigitations and focal tight junctions.
They communicate via gab junctions. Some nutrients are allowed to pass paracellularly to the remaining corneal layers indicating a semipermeable nature of the endothelial cell layer [ 18 ]. The corneal endothelium is a highly active tissue.
This is evident by the presence of numerous mitochondria, the prominent endoplasmic reticulum, ribosomes, and Golgi apparatus. The fluid is pumped out of the corneal stroma into the anterior chamber via pinocytic vesicles [ 18 ]. Generally, corneal dystrophies are defined as a group of progressive, inherited, mostly bilateral, and symmetric, variable corneal opacifying disorders, which are usually not related to environmental or systemic conditions.
The can be associated with blurred vision and ocular discomfort. Their onset is usually early in life but they manifest later clinically. They are slowly progressive and become more prominent with age. There are exceptions to the corneal dystrophies definition: some dystrophies are unilateral or bilateral asymmetric, some have no obvious heredity, and some have related systemic abnormalities [ 1 , 2 ].
In , the International Committee on the Classification of Corneal Dystrophies IC3D proposed a modified anatomic classification on the basis of the cellular origin of the corneal dystrophies consisting of [ 3 ]: Epithelial and subepithelial dystrophies. An evidence-based category system was suggested to indicate the level of evidence that supports the existence of a given corneal dystrophy.
In this system, each dystrophy is organized according to the clinical phenotype, with a template summarizing genetic, clinical, and pathologic information.
The system is upgradable and can be retrieved at www. The categories are as follows [ 23 ]: Category 1 C1 : a well-defined corneal dystrophy in which the gene has been mapped and identified and the specific mutations are known. Category 2 C2 : a well-defined corneal dystrophy that has been mapped to one or more specific chromosomal loci, but the gene s remains to be identified.
Category 3 C3 : a well-defined corneal dystrophy in which the disorder has not yet been mapped to a chromosomal locus. Category 4 C4 : this category is reserved for a suspected, new, or previously documented corneal dystrophy, although the evidence for it, being a distinct entity, is not yet convincing. In the following subsections, we will describe the clinical, genetic, and histopathologic characteristics of the common corneal dystrophies from anterior to posterior: epithelial and subepithelial, epithelial-stromal TGFBI , stromal, and endothelial dystrophies.
It was found to be more common in females [ 27 ]. Inheritance : mostly sporadic with familial cases have been reported. Thus, they are thought to be degenerative or caused by previous trauma.
Genetic locus and gene : 5q Category : most cases are sporadic. C1 in rare cases. Onset : usually in the second decade. Irregular astigmatism might cause decreased vision and monocular diplopia. The severity of pathology can fluctuate with time. Signs : can be isolated or combined and unilateral or bilateral. Maps: central or paracentral thickened, scalloped, circumscribed borders resembling coastlines, associated with faint haze. Fingerprints: paracentral, hair-like, curvilinear concentric lines, best visualized with retro-illumination.
Dots: central, round or oval, non-staining, intraepithelial opacities. These lesions contain debris of degenerated epithelial cells. Bleb pattern: subepithelial bleb or cobble stone-like pattern, best seen by retro-illumination. Histopathology : Maps: thickened intraepithelial, multilamellar, basement membrane.
Management : in asymptomatic cases no intervention is required. When symptoms occur, the frequent use of lubricants is recommended preferably preservative-free lubricants. Hypertonic drops i. Topical antibiotics are needed in cases where there are erosions. Cautious wear of a bandage contact lens may help in providing comfort and healing. In severe cases, debridement of the epithelial surface might be needed, and, in some cases, a phototherapeutic keratectomy PTK might be helpful.
Inheritance : autosomal dominant. Genetic locus and gene : unknown. Category : C3. Onset : childhood. Symptoms : recurrent epithelial erosion attacks that start in childhood and continue in adulthood. The attacks are usually nocturnal. Corneal opacification, which may be visually significant if located centrally, occurs in about half of the cases. Painful erosive episodes usually decrease with age.
Signs : repeated epithelial erosions lasting up to 7 days in duration. Typically, no signs can be detected after healing of the attack. However, central subepithelial opacities, subepithelial fibrosis, or corneal keloids may develop later in life.
Histopathology : the basal epithelial cells are irregular with distended intercellular spaces. Intracellular and intercellular Alcian blue-positive deposits are present. Avascular pannus is between the basal epithelium and the Bowman layer [ 3 ]. Management : in asymptomatic patients, treatment is not required.
Recurrent erosive episodes are treated as for recurrent epithelial erosions. Epithelial debridement may be necessary in patient with irregular astigmatism. Inheritance : mostly autosomal dominant.
Category : C4. Onset : early childhood. Symptoms : painful epithelial erosions that might decrease in frequency with age. The vision tends to deteriorate with time.
Signs : subepithelial haze denser in the center. Histopathology : subepithelial band of eosinophilic, periodic acid-Schiff PAS -positive, Alcian blue-positive, hyaluronidase-sensitive material is present anterior to the Bowman layer [ 3 ]. Management : recurrent erosive episodes are treated as for recurrent epithelial erosions.
Variant : stocker-Holt variant. Genetic locus and gene : 2 loci and 2 genes. Locus 12q13 KRT3 gene. Category : C1. Onset : usually in the first decade.
Symptoms : most patients are asymptomatic. Glare, photophobia, decreased vision, or recurrent epithelial erosions may occur. A year old female patient was referred to our clinic due to long-standing progressive right eye blurred vision. No relevant personal or familial history. On biomicroscopy examination, central subepithelial spiraled opacities were characteristic of Map-dot-fingerprint Dystrophy, also known as Epithelial Basement Membrane Dystrophy or Cogan's Microcystic Epithelial Dystrophy.
Pellucid marginal degeneration is a slowly progressive corneal ectatic condition often leading to severe visual impairment of working age people. The peripheral corneal thinning location requires a large graft size, eventually a peripheral lamellar crescentic keratoplasty followed by a central penetrating keratoplasty.
Besides surgically more challenging, corneal transplantation is associated to increased risk of vascularization and rejection. Dots, cysts and maps in the cornea of a patient complaining of suggestive recurrent corneal erosions episodes.
The cornea is crucial for refracting and focusing light—and therefore focusing your vision. The cornea is an extremely vital part of the eye and of your vision.
Corneal degenerations are changes or gradual deteriorations in the tissue of the cornea. They can negatively impact the function of the cornea, limiting its ability to help the eye focus properly.
Over time, corneal degenerations can cause loss of vision, eye pain, and other issues. The symptoms of corneal degeneration can vary significantly, as the condition has multiple varieties. Corneal degenerations can be caused by disease or by aging. In most cases, degenerations have nothing to do with genetics. Multiple diseases and conditions can be contributing causes of corneal degenerations.
Because these conditions have been linked with corneal degenerations, you should always provide a complete and accurate medical history to your eye doctor. The symptoms of a corneal degeneration can vary depending on the type of degeneration.
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