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Eric D. Donnenfeld, MD, AJ. Kanellopoulos, MD, Henry D. Perry, MD

ABSTRACT
Keratoconus, an ectatic, noninflammatory dystrophy of the central cornea, is a relatively common corneal disease. It presents challenging management problems to the ophthalmologist. The etiology of keratoconus is probably multifactorial, including heredity, biochemical abnormalities, and self-induced mechanical trauma. Treatment of keratoconus remains contact lens fitting, which is usually successful. A minority of patients require penetrating keratoplasty for visual rehabilitation.

INTRODUCTION
Keratoconus is a relatively common corneal disease and presents one of the most challenging management problems for the ophthalmologist. The diagnosis of keratoconus may be subtle. However, recent advances in corneal imaging have greatly aided in the diagnosis of this condition. Keratoconus is an ectatic, noninflammatory dystrophy of the central cornea. The disease is generally bilateral and occurs between the ages of 10 and 30.

Keratoconus typically progresses over a 5 to 10 year period before stabilizing. The onset may be asymmetric and progression may be varied. Most cases do not have a family history, although there have been well-described pedigrees.1-5 With the advent of videokeratography, more family members with asymmetric corneal features have been identified, suggesting a more important role for heredity.2

Keratoconus usually presents as myopic astigmatism. As it progresses, a cone may become visible. The cone is an ectatic protuberance of the cornea, characteristically rounded and slightly displaced inferonasally. However, cones may also be sagging, nipple-like, or oval and may vary significantly in size.6

E.D. Donnenfeld, A.J. Kanellopoulos, H.D. Perry - Department of Ophthalmology, North Shore University Hospital, Manhasset; Cornell University Medical College, New York 

DIAGNOSIS OF KERATOCONUS

In its early stages keratoconus may be difficult to diagnose on physical examination. The patient may complain of decreased visual acuity that is not refractable to 20/20. Comeal thinning and cone formation may not be visible with direct slit-lamp illumination. However, an oil-drop reflex is often visible with the slit-lamp, direct ophthalmoscope or keratoscope upon retro-illumination of the cornea. Keratoscopy reveals a classic scissors reflex. Quantitative evaluation may be performed with a keratometer, and in advanced cases comeal curvature may exceed 70 D.

In early cases, the irregular keratometer reflex may be diagnostic. However, placido disc technology is the most sensitive way to diagnose keratoconus. The use of the placid? disc or the hand-held keratoscope provides qualitative topographic information. Since the introduction of the photokeratoscope, quantitative determinations of the radii of curvature and peripheral corneal topography have been made. Photokeratoscopy often shows irregular oval-shaped mires with superior nasal flattening and inferior temporal steepening.

This technology has been largely superseded by videokeratography, which produces a color diopter map of the cornea (Fig. below). Videokeratography provides a quantitative and qualitative evaluation of the corneal contour. The color map allows visual inspection of the optical zone, centration, and regularity. Quantitative dioptric power is represented by the coloring of each point, with the pattern of color offering qualitative interpretation. This test is easily reproducible and does not require subjective input. With videokeratography the earliest subclinical stages of keratoconus may be discerned.7,8 In fact, there is controversy over whether these cases truly represent keratoconus or are only irregular astigmatism.

Recently, specialized software has been added to videokeratography devices to help aid in keratoconus detection. The study of the paracentral corneal topography is the most sensitive test for the diagnosis of keratoconus.7-l1 Videokeratography represents a significant advance in the detection of early keratoconus. According to present reports, the most useful parameters in the diagnosis of keratoconus from corneal topographical imaging are: (a) central corneal power, (b) the difference between the two eyes in central diopter power, and (c) the difference in inferior comeal steepening compared to superior.

The early detection of keratoconus is extremely important as a screening test for patients who are considering keratorefractive surgery. Incisional keratotomy has variable and unreliable results in patients with ectatic comeal changes and is not recommended.7 Excimer laser photoablation is also contraindicated in keratoconus.

KERATOCONUS - PHYSICAL FINDINGS

As keratoconus progresses, the comeal thinning and protuberance may become severe, and the diagnosis is readily made clinically. Physical signs include vertical stress lines on the deep comeal stroma, called Vogt's striae. These striae are due to comeal torsion related to the ectasia. Manual pressure to the cornea may temporarily remove these stress lines. Fine scarring of the anterior stroma may sometimes be noted at the apex of the cone. This scarring is secondary to the rupture of Bowman's membrane. A rupture of Bowman's membrane is a characteristic finding on pathological examination of a keratoconus corneal button.

In long-standing or severe keratoconus, an epithelial iron line known as a Fleischer ring may occur at the base of the cone. This finding is best seen on a cobaltblue slit-lamp examination. On downward gaze the cone may indent the lower lid. This finding is known as Munson's sign and occurs only in the most advanced cases. Finally, in severe cases, Descemet's membrane may rupture, producing an explosive episode of corneal edema known as acute corneal hydrops. Such patients develop severe stromal edema,often two to three times as thick as a normal cornea, as well as microcystic epithelial edema. Corneal hydrops generally resolve over a two to three month period as the endothelium slides over the tear in Descemet's membrane and pump function is restored. Following acute hydrops, the patient may be left with stromal scarring. Conversely, the cornea may be flattened, and visual acuity may improve with contact lens fitting. The tear in Descemet's membrane may produce a permanent DescemeVs scroll.

Acute hydrops is managed with the short-term use of a mild corticosteroid to treat the concomitant iritis and corneal inflammation. Hypertonic agents are generally ineffective but may be used in mild cases. Finally, intraocular pressure lowering agents, such as carbonic anhydrase inhibitors or beta blockers, may reduce the intraocular pressure which forces fluid into the cornea and may thereby reduce the severity of the corneal edema.

In 1991 we reported two cases of infectious keratitis related to contact lens wear in the setting of an acute hydrops.12 Both patients went on to corneal perforation. The tear in Descemet's membrane, strornal ederna, and epithelial bedewing associated with corneal hydrops results in the loss of the epithelial/endothelial barrier function of the cornea, creating a passageway for infectious organisms through the cornea. Acute hydrops associated with epithelial keratitis, stromal swelling, and a Descemet's membrane tear may be a significant risk factor for infectious keratitis and corneal perforation. Noninfec- tious corneal perforation with acute hydrops has recently been described.13,14 In some of these cases, pathologic examination of the cornea has revealed corneal fistulas extending from the tear in Descemet's membrane to Bowman's membrane. This fistula may serve as a conduit for infectious organisms into the anterior chamber. Our article recommended prophylactic, nontoxic, broad-spectrum antibiotics, as well as Seidel testing for aqueous leakage in all cases of severe hydrops.

PATHOGENESIS OF KERATOCONUS

Various authors have speculated that biochemical abnormalities may be responsible for the development of keratoconus. Studies have shown abnormalities in proteoglycans, proteoglycan location within the cornea, and proteoglycan metabolism.15,16 Several studies have shown that collagenolytic activity is markedly increased in keratoconus.17,18 Abnormalities in collagen fiber cross-linking have been documented.19 The association of keratoconus with systemic diseases based on biochemical abnormalities, such as Marfan's syndrome,20 Ehlers-Danlos syndrome,21 and osteogenesis imperfecta,22 adds further support to this theory.

The role of heredity in the development of keratoconus has not been clearly established. A genetic basis for keratoconus is supported by several of its recognized characteristics. For example, enantiomorphism, a high degree of non-superimposable mirror image symmetry between two eyes of the same individual, has been argued as supporting a hereditary basis.10 Keratoconus in identical twins has been documented.9 The majority of recent reports record a positive family history in 6% to 8% of patients with keratoconus.9 Finally, recent studies have found subtle corneal changes on videokeratography of clinically normal family members.2

Every possible mode of genetic transmission has been proposed,9 including both sex-linked transmission because of the predominance of females with keratoconus and recessive inheritance based on reports of parental intermarriage. Clearly, as noted by Krachmer et al.,9 the significance of the hereditary element must be evaluated independently of other potential systemic or local risk factors for this disease. Therefore, family members of patients with atopy or contact lens wear should be excluded. Also of significance is the diagnostic criteria for keratoconus or early keratoconus changes, since videokeratography is a very sensitive method of identifying clinically subtle changes in the comeal shape.

Von Ammon first described a familial occurrence of keratoconus in 1830.9 Several subsequent large series have documented family histories in patients with keratoconus. Rabinowitz et al. reported the results of videokeratography in 28 family members of patients with known keratoconus.7 Their findings identified 14 individuals who were normal on clinical examination and photokeratoscopic evaluation, but who had abnormalities on corneal videokeratography. They manifested central steepening - inferior to the apex especially - and substantial asymmetry in central diopter power between the fellow eyes. Genealogical analysis suggested an autosomal dominant mode of inheritance.

The authors of this report went on to suggest that with such heritability, keratoconus may either become fully expressed in its obvious clinical form or remain subclinical with forme fruste signs apparent on topography alone. The variable severity of the disease in monozygotic twins supports this theory.9 Further genetic analysis of families with strong vertical transmission may permit the localization of a gene for keratoconus. In any event, the child of a parent with kerato- conus has approximately a 1/100 chance of developing the same disease.

One of the most common associations of keratoconus is with eye rubbing. Ridley first discovered the relationship between keratoconus and atopic disease.23 In his study, 70% of keratoconus patients were noted to rub their eyes. Subsequent studies have confirmed his findings.24 Multiple authors have established a relationship between keratoconus and various atopic diseases, including eczema, hay fever, and spring ca- tarrh.25-27 Down syndrome, eye rubbing, and keratoconus have also been linked together.28,29 Five to eight percent of keratoconus patients have Down syndrome as a predisposing factor. In addition, the cones in Down syndrome tend to be more severe and are associated with a higher likelihood of acute comeal hydrops.

Further support for the mechanical theory of keratoconus is provided by the association of keratoconus with floppy eyelid syndrome. Floppy eyelid syndrome is a well-described clinical entity related to mechanical eversion of the upper lid while sleeping.

In 1991 we reported five cases of floppy eyelid syndrome with concomitant keratoconus. One of these patients had both bilateral keratoconus and bilateral symmetric floppy eyelid syndrome. The other four patients had asymmetric keratoconus and floppy eyelid syndrome.30 These four patients all gave a history of sleeping with their heads on the side with the more severe keratoconus and floppy eyelid syndrome. In asymptomatic patients with floppy eyelid syndrome, 9 of 10 patients were found to have topographic abnormalities on videokeratography.31

Whether or not the wearing of PMMA or gaspermeable contact lenses contributes to the development of keratoconus remains controversial.32,33 Rigid contact lenses can distort the comeal surface, causing irregular astigmatism and corneal warpage. However, the topography of these patients is different from that of classic keratoconus. Whether keratoconus proceeds to develop in these patients is uncertain. Most likely, biochemical abnormalities, genetic predisposition, and mechanical trauma all play a role in the development of keratoconus. As any exact cause of keratoconus remains elusive, the condition should be considered multifactorial.

MANAGEMENT OF KERATOCONUS

Early keratoconus can often be treated in the short term with spectacle correction. However, the mainstay of therapy is contact lens fitting, and the great majority of patients with keratoconus can be fit with contact lenses.34 Contact lens fitting in keratoconus is an art form that challenges the skill and patience of the contact lens practitioner. Most patients may be fit with small, steep, gas-permeable contact lenses, although a variety of contact lens types, including double posterior curve lenses, combined soft and hard lenses (piggyback lenses), gas-permeable lenses with a peripheral soft lens component, and even scleral contact lenses may be employed.

Surgical management of keratoconus is required in 10% to 20% of patients. Earlier literature suggested that lamellar keratoplasty, such as epikeratophakia, might be effective in the management of contact lens-intolerant patients. However, visual rehabilitation with epikeratophakia has generally been less effective than with penetrating keratoplasty.35 The major advantage of epikeratophakia is that it is an extraocular procedure and there is no risk of graft rejection. For these reasons, epikeratophakia is occasionally indicated in high-risk patients.

Penetrating keratoplasty is extremely successful in keratoconus. The visual success rate for a 20/40 or better graft is approximately 90%.3 The surgical technique for penetrating keratoplasty in keratoconus is varied, but most surgeons recommend a minimal (0.25 mm or less) disparity between donor and recipient bed. These transplantations may be difficult due to loss of scleral rigidity, positive vitreous pressure, and suturing into an ectatic corneal bed. Following corneal transplantation, keratoconus patients often have significant residual astigmatism greater than non-keratoconus patients with transplants. Approximately 60% of patients with keratoconus require contact lens fitting for visual rehabilitation following penetrating keratoplasty.36,37 Recently, the management of astigmatism in postkeratoconus comeal transplant patients has been successful with relaxing incisions and comeal wedge resections.

CONCLUSION

Keratoconus remains one of the most challenging conditions for the ophthalmologist. The diagnosis may be subtle, but it should be considered in any patient with myopic astigmatism who is difficult to refract. Videokeratography has greatly aided the diagnosis of this condition. Refractive surgery should be avoided in these patients, as the results are unpredictable. The etiology of keratoconus remains uncertain but is probably multifactorial, involving heredity, biochemical abnormalities, and mechanical trauma. The preferred treatment of keratoconus remains contact lens fitting, which is usually very successful. The minority of pa- tients who require penetrating keratoplasty for visual rehabilitation also have an excellent visual prognosis.

Acknowledgement: This research was supported in part by the Lions Club International Foundation, Oakbrook, Illinois.

REFERENCES