Overview
Loss or reduction in corneal transparency occurs from a variety of causes, including edema resulting from diseases such as Fuchs’ dystrophy and bullous keratopathy, scarring resulting from wound healing, haze following photorefractive keratectomy, and certain metabolic diseases such as corneal macular dystrophy. The intent of this chapter is to review the present understanding of mechanisms or structural alterations that cause loss of corneal transparency. Transparency loss resulting from edema, scarring, and photorefractive keratectomy will be emphasized.
Understanding the mechanisms of transparency loss requires understanding the structural bases of corneal transparency itself. Because the cornea does not absorb light in the visible portion of the electromagnetic spectrum, its transparency is the result of minimal light scattering. Visible light is an electromagnetic wave with wavelengths between 400 and 700 nm. Light scattering results when an incident light wave encounters fluctuations in the refractive index of a material. These fluctuations cause some of the light to be redirected from the incident direction, thus reducing the irradiance in the forward direction. The transmissivity, F T , is defined as:
F T = I ( t ) I 0 = e x p ( − α s c a t t )
Collagen fibrils, which lie parallel to one another within the lamellae of the corneal stroma, have a somewhat larger refractive index than the optically homogeneous ground substance surrounding them. Thus they scatter light. In fact, because they are so numerous they would scatter approximately 60% of an incident beam of light having a wavelength of 500 nm if they were randomly arranged like gas molecules and therefore scattered independently of one another (i.e., F T would be 0.40). A normal cornea scatters only about 5% of 500 nm light ; thus transparency theories seek to explain why the scattering is so small ( Box 1.1 ). The key is that destructive interference among the scattered fields, which arises because the fibrils possess a certain degree of spatial ordering about one another, reduces the scattering that would otherwise occur. Indeed, Maurice’s lattice theory of transparency postulated that the fibrils within the stromal lamellae are arranged in a perfect hexagonal lattice. Because their spacing (which is approximately 60 nm) is less than the wavelength of visible light, Bragg scattering cannot occur and such an arrangement leads to perfect transparency. Obviously the corneal stroma is not perfectly transparent. If it were, it could not be visualized in the slit-lamp microscope. Although scattering from keratocytes could be used to explain visibility in the slit lamp, all present evidence suggests that they are not a significant source of scattering in normal cornea except under the specialized condition of specular scattering that occurs in confocal images or in the slit lamp when the incident and viewing directions are configured to make equal angles with the surface normal. Additionally, transmission electron micrographs (TEM) of the normal stroma do not depict a perfect lattice arrangement ( Figure 1.1 ). Thus, as described in the remainder of this section, investigators have built on the Maurice model by relaxing the condition of perfect crystalline order.
- •
The matrix of collagen fibrils is the major source of light scattering in normal cornea
- •
Keratocytes are not a significant source of scattering in normal cornea except under the specialized condition of specular scattering
- •
Measurements of how the total scattering cross-section depends on light wavelength can be used to distinguish between the various transparency theories
Scattering from an array of parallel cylindrical collagen fibrils is characterized by a quantity σ t (λ), called the total scattering cross-section. It is equal to σ 0t (λ)σ tN (λ), where σ 0t (λ) is the total scattering cross-section per unit length of an isolated fibril, σ tN (λ) is the interference factor, and λ is the wavelength of light in the stroma. 8 The total scattering cross-section per unit length of an isolated fibril, σ 0t (λ), depends on the fourth power of fibril radius and the ratio of the fibril index of refraction to that of its surroundings and its wavelength dependence is inverse cubic (i.e., σ 0t (λ) ~ 1/λ 3 ). The interference factor, σ tN (λ), is the subject of all modern transparency theories. These have been reviewed extensively elsewhere and will not be discussed in detail here. The value of the interference factor varies between zero (for Maurice’s perfect lattice theory) and one (for fibrils with random positions – the independent scattering result discussed above). In order to agree with experimental values of transmissivity, its value is about 0.1 at a wavelength of 500 nm ( Box 1.2 ).
Corneal transparency is due to three major factors:
- •
Individual fibrils are ineffective scatterers because of their small diameter and their refractive index is relatively close to the surrounding ground substance (the ratio is ~ 1.04)
- •
Destructive interference among the scattered fields reduces the scattering by a factor of ~10 over that which would occur if the fibrils scattered independently of one another
- •
The cornea is thin
Measurements of how the total scattering cross-section depends on light wavelength can be used both to distinguish between the various transparency theories, and to distinguish between types of structural alterations that reduce transparency. The total scattering cross-section can be determined by measuring transmissivity as a function of light wavelength and noting that the extinction coefficient α scat for cornea (cf., Equation 1 ) is given by ρσ t (λ), where ρ is the number of fibrils per unit area in a cross-section of a corneal lamella (usually called the fibril number density). Details have been discussed elsewhere. The results of such measurements indicate that ρσ t (λ) (where ρ is simply a number) is proportional to 1/λ 3 (i.e., the total scattering cross-section has the form A /λ 3 , where A is a constant that depends on the fibril radius and the fibril refractive index relative to that of the ground substance). Because the scattering cross-section of an isolated fibril, σ 0t (λ), has this same dependence, the structure factor of normal corneal stroma must be essentially independent of wavelength. This is in accordance with the short-ranged order theory of Hart and Farrell, which is based on the structures shown in TEM ( Figure 1.1 ), as well as with the correlation area theory of Benedek and the hard-core coating theory of Twersky. It is in disagreement with theories based on long-range order in fibril positions (e.g., Feuk’s disturbed lattice theory), which predict that the total scattering cross-section would vary as 1/λ 5 .
Transparency loss from corneal edema
It has been known for well over a century that swollen corneas become cloudy, thus reducing their transparency. Corneal swelling is induced by causes such as endothelial or epithelial damage, bullous keratopathy, and Fuchs’ corneal dystrophy. In this section, the structural alterations underlying the loss of transparency in edematous corneas are discussed ( Box 1.3 ).
- •
Edematous corneas appear cloudy due to increased light scattering
- •
Transmission electron micrographs of edematous corneas show mildly disordered fibrillar distributions and regions called “lakes” where fibrils are missing
- •
Lakes would cause large fluctuations in the refractive index, which would increase light scattering
- •
Lakes alter the form of the total scattering cross-section in a manner that can be tested by light-scattering measurements
- •
Measurements of the wavelength dependence of the total scattering cross-section are consistent with the presence of lakes, confirming that they are not fixation artifact
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Overview
Loss or reduction in corneal transparency occurs from a variety of causes, including edema resulting from diseases such as Fuchs’ dystrophy and bullous keratopathy, scarring resulting from wound healing, haze following photorefractive keratectomy, and certain metabolic diseases such as corneal macular dystrophy. The intent of this chapter is to review the present understanding of mechanisms or structural alterations that cause loss of corneal transparency. Transparency loss resulting from edema, scarring, and photorefractive keratectomy will be emphasized.
Understanding the mechanisms of transparency loss requires understanding the structural bases of corneal transparency itself. Because the cornea does not absorb light in the visible portion of the electromagnetic spectrum, its transparency is the result of minimal light scattering. Visible light is an electromagnetic wave with wavelengths between 400 and 700 nm. Light scattering results when an incident light wave encounters fluctuations in the refractive index of a material. These fluctuations cause some of the light to be redirected from the incident direction, thus reducing the irradiance in the forward direction. The transmissivity, F T , is defined as:
F T = I ( t ) I 0 = e x p ( − α s c a t t )
Collagen fibrils, which lie parallel to one another within the lamellae of the corneal stroma, have a somewhat larger refractive index than the optically homogeneous ground substance surrounding them. Thus they scatter light. In fact, because they are so numerous they would scatter approximately 60% of an incident beam of light having a wavelength of 500 nm if they were randomly arranged like gas molecules and therefore scattered independently of one another (i.e., F T would be 0.40). A normal cornea scatters only about 5% of 500 nm light ; thus transparency theories seek to explain why the scattering is so small ( Box 1.1 ). The key is that destructive interference among the scattered fields, which arises because the fibrils possess a certain degree of spatial ordering about one another, reduces the scattering that would otherwise occur. Indeed, Maurice’s lattice theory of transparency postulated that the fibrils within the stromal lamellae are arranged in a perfect hexagonal lattice. Because their spacing (which is approximately 60 nm) is less than the wavelength of visible light, Bragg scattering cannot occur and such an arrangement leads to perfect transparency. Obviously the corneal stroma is not perfectly transparent. If it were, it could not be visualized in the slit-lamp microscope. Although scattering from keratocytes could be used to explain visibility in the slit lamp, all present evidence suggests that they are not a significant source of scattering in normal cornea except under the specialized condition of specular scattering that occurs in confocal images or in the slit lamp when the incident and viewing directions are configured to make equal angles with the surface normal. Additionally, transmission electron micrographs (TEM) of the normal stroma do not depict a perfect lattice arrangement ( Figure 1.1 ). Thus, as described in the remainder of this section, investigators have built on the Maurice model by relaxing the condition of perfect crystalline order.
- •
The matrix of collagen fibrils is the major source of light scattering in normal cornea
- •
Keratocytes are not a significant source of scattering in normal cornea except under the specialized condition of specular scattering
- •
Measurements of how the total scattering cross-section depends on light wavelength can be used to distinguish between the various transparency theories
Scattering from an array of parallel cylindrical collagen fibrils is characterized by a quantity σ t (λ), called the total scattering cross-section. It is equal to σ 0t (λ)σ tN (λ), where σ 0t (λ) is the total scattering cross-section per unit length of an isolated fibril, σ tN (λ) is the interference factor, and λ is the wavelength of light in the stroma. 8 The total scattering cross-section per unit length of an isolated fibril, σ 0t (λ), depends on the fourth power of fibril radius and the ratio of the fibril index of refraction to that of its surroundings and its wavelength dependence is inverse cubic (i.e., σ 0t (λ) ~ 1/λ 3 ). The interference factor, σ tN (λ), is the subject of all modern transparency theories. These have been reviewed extensively elsewhere and will not be discussed in detail here. The value of the interference factor varies between zero (for Maurice’s perfect lattice theory) and one (for fibrils with random positions – the independent scattering result discussed above). In order to agree with experimental values of transmissivity, its value is about 0.1 at a wavelength of 500 nm ( Box 1.2 ).
Corneal transparency is due to three major factors:
- •
Individual fibrils are ineffective scatterers because of their small diameter and their refractive index is relatively close to the surrounding ground substance (the ratio is ~ 1.04)
- •
Destructive interference among the scattered fields reduces the scattering by a factor of ~10 over that which would occur if the fibrils scattered independently of one another
- •
The cornea is thin
Measurements of how the total scattering cross-section depends on light wavelength can be used both to distinguish between the various transparency theories, and to distinguish between types of structural alterations that reduce transparency. The total scattering cross-section can be determined by measuring transmissivity as a function of light wavelength and noting that the extinction coefficient α scat for cornea (cf., Equation 1 ) is given by ρσ t (λ), where ρ is the number of fibrils per unit area in a cross-section of a corneal lamella (usually called the fibril number density). Details have been discussed elsewhere. The results of such measurements indicate that ρσ t (λ) (where ρ is simply a number) is proportional to 1/λ 3 (i.e., the total scattering cross-section has the form A /λ 3 , where A is a constant that depends on the fibril radius and the fibril refractive index relative to that of the ground substance). Because the scattering cross-section of an isolated fibril, σ 0t (λ), has this same dependence, the structure factor of normal corneal stroma must be essentially independent of wavelength. This is in accordance with the short-ranged order theory of Hart and Farrell, which is based on the structures shown in TEM ( Figure 1.1 ), as well as with the correlation area theory of Benedek and the hard-core coating theory of Twersky. It is in disagreement with theories based on long-range order in fibril positions (e.g., Feuk’s disturbed lattice theory), which predict that the total scattering cross-section would vary as 1/λ 5 .
Transparency loss from corneal edema
It has been known for well over a century that swollen corneas become cloudy, thus reducing their transparency. Corneal swelling is induced by causes such as endothelial or epithelial damage, bullous keratopathy, and Fuchs’ corneal dystrophy. In this section, the structural alterations underlying the loss of transparency in edematous corneas are discussed ( Box 1.3 ).
- •
Edematous corneas appear cloudy due to increased light scattering
- •
Transmission electron micrographs of edematous corneas show mildly disordered fibrillar distributions and regions called “lakes” where fibrils are missing
- •
Lakes would cause large fluctuations in the refractive index, which would increase light scattering
- •
Lakes alter the form of the total scattering cross-section in a manner that can be tested by light-scattering measurements
- •
Measurements of the wavelength dependence of the total scattering cross-section are consistent with the presence of lakes, confirming that they are not fixation artifact
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