Although investigating the ultrastructural basis for haze was not a direct part of this study, several comments are warranted. Several investigators have reviewed potential contributing factors to haze.
22 50 51 52 Among the potential histopathological features are: increased numbers of keratocytes,
53 54 55 56 vacuoles within and around keratocytes,
55 56 myofibroblast generation,
42 45 discontinuous and convoluted basement membrane structures,
56 57 58 and disorganized fibrillar and lamellar structures.
55 56 58 59 60 Understanding the cause(s) of increased scattering requires an understanding of the structural factors that underlie the transparency of normal cornea. In the normal rabbit cornea, the stroma accounts for approximately 80% of the small amount of green light scattered at 120°. The other 20% is from the surface of the epithelium and from the endothelium.
61 In the normal cornea, under
nonspecular illumination conditions, the matrix of collagen fibrils is the primary source of the small amount of stromal scattering that is observed.
50 62 63 Under specular scattering conditions the keratocytes, which normally lie rather flat between the lamellae, act like small mirrors and become the predominate source of scattering.
50 62 63 64 Transparency of the normal cornea results from three factors: the cornea is thin; the individual collagen fibrils are weak scatterers; and interference among the waves scattered from different parallel fibrils reduces the scattering by about one order of magnitude from that which would occur if the fibrils scattered independently of one another.
50 65 66 67 68 Inspection of micrographs
55 56 58 and confocal images
23 45 of excimer-treated corneas indicates that activated keratocytes (or myofibroblasts) have a different morphology than those in normal cornea and they are frequently tilted at a variety of angles, possibly as a result of the disrupted lamellar structure. This would have the effect of creating a variety of specular angles, one for each different tilt angle, thus possibly increasing the cellular contribution to scattering. In addition, there is evidence that the refractive index of activated keratocytes (or myofibroblasts) is different from that of normal keratocytes, which could alter their contribution to scattering.
69 Vacuoles within and around keratocytes may act like the voids or “lakes” that are observed in the fibril distribution of highly scattering, edematous corneas. Such voids introduce spatial fluctuations in the index of refraction and therefore could lead to increased light scattering.
66 67 70 Indeed, it has been demonstrated that similar voids in the fibril distribution are responsible for the increased scattering in cold-swollen rabbit corneas.
66 67 70 Light scattered from different fibrils in the disorganized lamellae that lack the orderly parallel arrangement of fibrils characteristic of normal cornea cannot interfere. Thus, the approximately 10-fold reduction in scattering that results from the destructive interference that occurs in normal cornea would be lost and the fibrils would act as independent scatterers. Finally, proteoglycans in the ground substance may be altered during the healing process.
55 Such alterations might change the refractive index difference between the fibrils and ground substance, which would either increase or decrease the fibrillar scattering contribution, depending on whether the difference increased or decreased.