PATHOLOGY There is diffuse thickening and lamination of the Descemet membrane, with sparse atrophic endothelial cells. On electron microscopy, multiple layers of basement membrane–like material are seen on the posterior part of Descemet membrane along with degeneration of the endothelial cells with many vacuoles. Stromal thickening with severe disorganization and disruption of the lamellar pattern is evident.
CLINICAL FINDINGS CHED2 is congenital and stationary but more severe than CHED1. Corneal clouding ranges from a diffuse haze to a “ground glass” appearance, with occasional focal gray spots. Thickening of the cornea (2–3 times normal) occurs (Fig 10-23), with rare subepithelial band keratopathy and IOP elevation. Blurred vision and nystagmus occur with minimal to no tearing or photophobia.
Figure 10-23 CHED2, showing diffuse stromal thickening. (Reproduced with permission from Weiss JS, Møller H, Lisch W, et al. The IC3D classification of the corneal dystrophies. Cornea. 2008;27(10:Suppl 2):S29.)
MANAGEMENT Because corneal clouding is more common and severe in CHED2 than in CHED 1, corneal transplantation is required at an earlier age.
Ectatic Disorders
Keratoconus
Keratoconus is a common disorder (prevalence of about 1 per 2000) in which the central or paracentral cornea undergoes progressive thinning and bulging, such that the cornea takes on the shape of a cone (Fig 10-24; see also Fig 10-31). The hereditary pattern is not prominent or predictable, but positive family histories have been reported in 6%–8% of cases. Clinically unaffected first-degree relatives have a higher chance of showing subclinical topographic abnormalities associated with keratoconus than does the general population. Multiple chromosomal loci have been reported, but the identification of specific genes remains elusive. The combination of genetic and environmental risk factors such as eye rubbing, inflammation, atopy, hard contact lens wear, and oxidative stress all play a role in the onset and progression of keratoconus.
Kiliç A, Colin J. Advances in the surgical treatment of keratoconus. Focal Points: Clinical Modules for Ophthalmologists. San Francisco: American Academy of Ophthalmology; 2012, module 2.
McMonnies CW. Abnormal rubbing and keractectasia. Eye Contact Lens. 2007;33(6 Pt 1):265–271.
Figure 10-24 Keratoconus.
PATHOLOGY Histologically, keratoconus shows the following:
fragmentation of the Bowman layer
thinning of the stroma and overlying epithelium folds or breaks in the Descemet membrane
variable amounts of diffuse scarring
CLINICAL FINDINGS Nearly all cases are bilateral, but 1 eye may be much more severely involved. Sometimes the less affected eye shows only high astigmatism, which may be considered the minimal manifestation of keratoconus. Alternatively, videokeratoscopy may show enantiomorphism (a mirror image) and reveal some mild steepening in the other eye. The disease tends to progress during the adolescent years and into the mid-20s and 30s, although progression can occur at any time. Early biomicroscopic and histologic findings include fibrillation of the Bowman layer, leading to breaks and followed by fibrous growth and dysplasia through the break. As progression occurs, the apical thinning of the central cornea worsens, and extreme degrees of irregular astigmatism can develop. No associated inflammation occurs.
Scissoring of the red reflex on ophthalmoscopy or retinoscopy is a very early sign of keratoconus. Rizzutti sign, a conical reflection on the nasal cornea when a penlight is shone from the temporal side, is another early finding (Fig 10-25). Munson sign is evident as a protrusion of the lower eyelid upon downgaze (Fig 10-26). Iron deposits are often present within the epithelium around the base of the cone and constitute a Fleischer ring (Fig 10-27), a brown ring best seen with the cobalt blue filter using a broad, oblique beam. Fine, relucent, and roughly parallel striations (Vogt lines), or stress lines, of the posterior stroma can be observed. Focal ruptures and flecklike scars occur in the Bowman layer.
Figure 10-25 Rizzutti sign (arrow).
Figure 10-26 Munson sign. (Courtesy of James R. Reidy, MD.)
Figure 10-27 Keratoconus showing a Fleischer ring (arrow). (Courtesy of James J. Reidy, MD.)
Spontaneous perforation in keratoconus is extremely rare. However, a tear can occur in the Descemet membrane at any time, resulting in the sudden development of corneal edema, or acute hydrops. Allergy and eye rubbing are risk factors for the development of hydrops. The break in the posterior cornea usually heals spontaneously in 6–12 weeks; the corneal edema then disappears, but stromal scarring may be left in its wake. Some patients regain good vision following the resolution of hydrops, depending largely on the extent and location of the scar.
An increased prevalence of keratoconus has been reported in Down syndrome, atopy, Marfan syndrome, floppy eyelid syndrome, Leber congenital hereditary optic neuropathy, and mitral valve prolapse. Keratoconus also occurs commonly in numerous congenital anomalies of the eye.
EVALUATION Computerized videokeratography is helpful in detecting early keratoconus, in following its progression, and in helping to fit contact lenses. Placido disk–based topography shows inferior steepening in the power map, but pachymetry mapping shows the thin zone to be paracentral (Fig 10-28). Ultrasonic pachymetry may be more accurate, however. Computerized videokeratography algorithms to diagnose forme fruste, or subclinical, keratoconus are continually being perfected to identify keratoconus suspects and screen prospective refractive surgery patients for keratoconus. Scanning slit and other elevation-based systems continue to be improved to measure deviation above a “best-fit sphere.” See Chapter 2 in this volume, as well as BCSC Section 3, Clinical Optics, and Section 13, Refractive Surgery.
Belin MW, Rodila JF. Topographic analysis in keratorefractive surgery. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea. 2nd ed. Vol 2. Philadelphia: Elsevier/Mosby; 2005:1909–1922.
Rao SN, Raviv T, Majmudar PA, Epstein RJ. Role of Orbscan II in screening keratoconus suspects before refractive corneal surgery. Ophthalmology. 2002;109(9):1642–1646.
Figure 10-28 Keratoconus. A, Placido disk computerized videokeratography demonstrating inferior steepening. B, Orbscan computerized videokeratography showing a pachymetry map of the same eye as in A. Note that the thinnest zone is near the visual axis and not at the steepest point.
MANAGEMENT Some cases of keratoconus are mild enough, at least for a time, that vision can be corrected adequately with glasses. However, rigid or gas-permeable contact lenses are far more helpful in all but the mildest cases. Their ability to neutralize the irregular corneal astigmatism often produces dramatic improvement in vision. Most patients with keratoconus without central corneal scarring can be fitted successfully with contact lenses. A central subepithelial scar can, on occasion, be removed (nodulectomy), allowing continued wear of contact lenses. Intrastromal rings and collagen crosslinking, two additional treatment modalities, can be used to flatten and centralize the cone as well as stabilize progression; in some cases, they can also improve vision and facilitate the use of contact lenses.
Indications for corneal transplantation include the following:
contact lens intolerance even with good vision
poor vision even with a comfortable contact lens fit (usually due to scarring)