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Etiology, Diagnosis, and Management of Keratoconus: New Thoughts and New Understandings

Patrick Caroline, COT, FAAO

Mark Andre, FAAO

Beth Kinoshita, OD

Jennifer Choo, OD

College of Optometry, Pacific University
2043 College Way
Forest Grove, OR 97116




Associated Conditions

Keratoconus has been associated with a number of systemic conditions including Down’s Syndrome (trisomy of chromosome 21). A number of authors have reported that the incidence of keratoconus in Down’s Syndrome is between 5.5% and 15%, which is considerably higher that the incidence of approximately 5 per 10,000 (0.05%) cited for the general population. Occasionally, keratoconus is also seen in individuals with connective tissue disorders such as Osteogenesis Imperfecta, Ehlers-Danlos Syndrome, and joint hypermobility.


Hallmarks of Keratoconus

Although the etiology of keratoconus remains somewhat obscure, its clinical manifestations have been well documented. Some on the major hallmarks of keratoconus include:


Types of Keratoconus

In clinical practice, three distinct forms of keratoconus have been identified, each with a unique clinical presentation. Differentiating between the three forms can be helpful in counseling patients about what to expect regarding eventual progression of the disease.

However, the clinical classification of keratoconus should be viewed as only a general guide. It is important to communicate to the patient that the condition can be extremely unpredictable and that its ultimate course can only be determined with time.

Puberty-Onset Keratoconus

Puberty-onset keratoconus is by far the most common form of the condition, and, as its name indicates, it begins in early adolescence at about age 14 to16 years. The condition is usually bilateral with one eye affected more than the other. Following its onset, there is often a dramatic progression of the condition for the next 8 to 10 years. This is typically followed by a period in which the condition seems to stabilize.

Clinical experience has shown that the earlier in life the keratoconus occurs, the more severe the condition will be. Therefore, a 12-year old, exhibiting the optical and topographical manifestations of early keratoconus is more likely to have a more severe form of the condition than an individual that shows similar findings in their late twenties.

Late-Onset Keratoconus

In late-onset keratoconus, the earliest signs and symptoms begin in the late twenties or early thirties. Both eyes are frequently affected to a similar degree, with little or no asymmetry. This is often a more benign form of the condition, and, unlike puberty-onset keratoconus, its progression is significantly less severe, rarely requiring surgical intervention in the form of a corneal transplant.

Keratoconus Fruste

The third form of keratoconus is called “form fruste” and was first described by Amsler in 1937. It is essentially an extremely mild form of keratoconus that can occur at anytime throughout life. The condition manifests as a central or para-central zone of irregular astigmatism of unknown etiology. The most striking hallmark of form fruste keratoconus is its lack of progression with the condition staying stable throughout the patient's life.


Use of Corneal Topography for Assessment of Keratoconus

In clinical practice, we use the term keratoconus to describe an entire spectrum of diversely shaped conditions in which the only common denominator may be central or paracentral corneal steepening. Yet, it is the topography beyond the central and paracentral cornea that can significantly influence the optics of the cornea and ultimately the success or failure of a contact lens design. Therefore, to better understand modern keratoconus contact lens fitting techniques, it is imperative to appreciate the diverse central and mid-peripheral topography changes associated with the condition. These are best assessed by use of a corneal topographer in which the circular light patterns (often referred to as Placido rings or mires) are projected onto the cornea and their reflections analyzed.

Dekking in 1920, and later Amsler in 1932, provided the first descriptions of topographical changes that occur in keratoconus by using early photokeratoscopy techniques. The system introduced by Amsler allowed him to classify keratoconus into four stages:

More recently, Reynolds, Bronstein, and Rowsey have described the geometry of a keratoconic eye based on photographs obtained using the Corneascope instrument. Tomlinson, Schwartz, Townsley, and Wesley have also contributed to our understanding of the corneal topography in keratoconus through the use of a Photo Electric Keratometer. Modern advances in computer-based analysis of keratoscopy images have produced an even greater understanding of the topographic patterns manifest in early as well as late stage keratoconus.

Modern photokeratoscopy and videokeratography (corneal mapping) techniques have demonstrated that in early keratoconus there is characteristically a pear-shaped pull of the central keratoscopy rings, with steepening initially occurring inferiorly, usually in the temporal quadrant. (Figure 7.) The steeper the corneal curvature, the higher the plus dioptric power of the cornea and the more closely spaced the topographic ring reflections will be. Also, rings that are not circular represent areas of optical distortion on the surface of the cornea.


Figure 7. Photokeratoscopy view of early keratoconus. Note the pear-shaped pulling of the central keratoscopy mires. The close proximity of the rings (in the inferior-nasal portion of the eye) indicates corneal steepening and greater distance between the rings (in the superior-nasal portion of the eye) indicates flattening.


In the early stage of keratoconus as illustrated in Figure 7, the superior cornea (above the corneal midline) remains relatively unaffected and therefore “normal” in curvature, similar to that of a non-keratoconic eye. This combination of topographic findings—pear-shaped infero-temporal steepening and normal curvature of the superior half of the cornea, should be considered extremely suspect of early keratoconus.

Additionally, the flatter, more “normal” superior corneal topography becomes the most important consideration in fitting rigid contact lenses for keratoconus, for it is at the flatter superior portion of the cornea that the rigid lens will be tightest.

As previously noted, the earliest topographical change in keratoconus is a paracentral steepening most commonly located in the inferior-temporal quadrant. As the condition progresses, the steepening spreads nasally to include the inferior (6 o’clock) and inferior-nasal corneal areas.

In advanced forms of the keratoconus, rotational steepening occurs at and above the midline along a path that eventually includes the temporal, superior-temporal, and superior (12 o’clock) cornea. The superior-nasal quadrant of the cornea is always the last to be affected, and thus an “island” of normal corneal topography often remains in this area even in the more advanced stages of the condition. (Figure 8.)


Figure 8. The typical spiral pattern of keratoconus progression. The condition commonly begins in the inferior-temporal quadrant, with the last area of the cornea to be topographically affected in the superior-nasal quadrant. In color-coded topographic images, red represents steeper corneal curvature, and the spectrum of yellow, green, and blue represents progressively flatter curvatures.


Additionally, even in the advanced forms of keratoconus the superior 3 to 4 mm of the cornea often retains a relatively normal curvature. Although there are exceptions to this pattern, the vast majority of keratoconic eyes have been noted to follow this spiral progression.

Many topographical changes occur well beyond the area evaluated by the conventional keratometer. Therefore, photo-keratoscopy and videokeratoscopy have become essential in documenting the complex topographic changes that occur in keratoconus. Furthermore, as will be discussed later, modern contact lens management of keratoconus depends almost entirely upon adequate documentation and understanding of topographic abnormalities that occur beyond the central apex of the cornea.


Corneal Topography in Advanced Keratoconus

Modern topographic techniques have demonstrated that in early keratoconus there is a characteristic steepening initially occurring mid-peripherally below the corneal midline. This is demonstrated by close proximity of the keratoscopy rings to one another. Above the midline, the superior cornea remains relatively normal in curvature. As the condition progresses, individual corneas can take on a wide range of topographical shapes that have been classified as “nipple,” “oval,” and “globus.” (Figure 9.)


Figure 9. The three topographical shapes of advanced keratoconus: nipple, oval, and globus.


Nipple-Shaped Topography

The nipple form of keratoconus characteristically consists of a small, near central ectasia, less than 5.0 mm in cord diameter. (Figure 10.)


Figure 10. The nipple-shaped form of keratoconus demonstrates a small central ectasis surrounded by 360 degrees of “normal” cornea.


The most striking features of the nipple topography are:

Figure 11. Nipple-shaped keratoconus may also manifest as a small central ectasia with moderate to high with-the-rule corneal astigmatism


Figure 12. An elevated fibroplastic nodule seen in a patient with moderate nipple shaped keratoconus. The superficial nodules frequently erode beneath the contact lens, resulting in an epithelial defect.


Figure 13. Epithelial erosion and “spiral staining” of a fibroplastic nodule. Piggyback lenses are frequently used to manage this condition.


Figure 14. Superficial keratectomy of a para-central nodule in keratoconus. Note the change in the central photokeratoscopy image pre- and post-keratectomy.


The overall topography of nipple-form keratoconus creates numerous fitting obstacles. The extremely rapid change in curvature from the steeper center to the more normal mid-peripheral cornea makes the nipple-form of keratoconus the most difficult to manage with rigid contact lenses alone.

Although difficult to fit with contact lenses, the nipple-shaped topography may be ideally suited for keratoplasty surgery. The small-diameter central location of the cone permits complete removal of the diseased portion of the cornea within the area of trephination. The 360° of relatively normal recipient cornea creates an optimum bed for wound closure and helps to minimize post-operative corneal astigmatism.

Oval-Shaped Topography

The most common corneal shape noted in advanced keratoconus is oval topography. In oval-form keratoconus, the corneal apex is displaced well below the midline resulting in varying degrees of inferior mid-peripheral steepening. The result of this “pushing out” of the cornea inferiorly is an island of normal or flatter-than-normal superior cornea, located exactly 180 degrees away. (Figures 15 and 16.)


Figure 15. Oval-shaped keratoconus is hallmarked by steepening of the inferior cornea.


Figure 16. Photokeratoscopy of an oval shaped cone shows the inferior-nasal steepening as noted by the close proximity of the keratoscopy lines and the superior-nasal flattening 180 degrees away, resulting in an “island” of normal cornea above the corneal midline.


Globus-Shaped Topography

The globus form of keratoconus affects the largest area of the cornea, often encompassing nearly three quarters of the corneal surface. Due to its size, nearly all of the keratoscopy rings will be encompassed within the area of the ectasia. (Figure 17.) Unlike the advanced forms of nipple or oval keratoconus, the globus cone has no island of “normal” mid-peripheral cornea above or below the midline.


Figure 17. Due to the size of the globus-shaped keratoconus, all nine rings of the photokeratoscopy image are encompassed by the conical area and no “islands” of normal mid-peripheral cornea are seen.


The various corneal shapes (nipple, oval, and globus) are most likely the result of simple apex location as well as yet unidentified stromal factors controlling mid-peripheral corneal shape. There is little doubt that the various central and mid-peripheral topographies will ultimately influence the final contact lens parameters. Therefore, it is imperative that we appreciate the diverse symmetrical and asymmetrical presentations seen in keratoconus. This is best accomplished through quantitative corneal surface analyses by photokeratoscopy and/or video keratography mapping techniques. Through this analysis the steepest and flattest portions of the cornea can be identified and this will help to clarify many of the peculiar fluorescein patterns noted during our diagnostic lens evaluation.

Alternately, the three keratoconus topographies (nipple, oval, and globus) can be visualized through a technique called “photodiagnosis.” Using photodiagnosis, the red fundus reflex is viewed through a direct ophthalmoscope at a distance of approximately two feet (60 cm) and/or photographed using a fundus camera. (Figure 18.) The technique allows for direct visualization of the size, shape, and location of the conical area for classification of nipple, oval, or globus keratoconus. (Figure 19.)


Figure 18. The three forms of keratoconus (nipple, oval, and globus) can be visualized directly by observing the red fundus reflex through a dilated pupil with a direct ophthalmoscope.


Figure 19. The photodiagnosis technique demonstrates the size, shape, and location of the conical area.


Keratoconus Detection Software

Today, many of the modern corneal topography systems incorporate specific keratoconus software to aid in the detection and subsequent clinical diagnosis of keratoconus. One of the more popular versions of this software is the Humphrey Atlas Pathfinder Corneal Analysis System ( The software performs an analysis of three indices of the individual patient’s corneal topography:

The patient’s topographical analysis is then compared to known normal and abnormal (keratoconic) eyes, and the software classifies the patient’s topography as "normal," "corneal distortion," or "keratoconus suspect." The Pathfinder software displays the control (normal) indices on three color bars:

The black arrow indicates the individual patient’s topographic values. (Figure 20.)


Figure 20. Output from the Humphrey Pathfinder keratoconus detection software. The black arrows indicate the patient’s individual topographic values as compared to a large cohort of normal and abnormal eyes.


The Corneal Irregularity Measurement (CIM) is a number or index assigned to represent the irregularity of the corneal surface. The higher the number, the more uneven or irregular the corneal surface. A high CIM value would tend to indicate a more advanced form of keratoconus with greater amounts of irregular astigmatism present in the central cornea. CIM uses thousands of data points within the first 10 rings of the corneal topography image to determine the difference in “height” or elevation between the patient’s cornea and a perfect toric model cornea.

The difference between the perfect model and the actual cornea is measured in microns with "normal," "borderline," and "abnormal" values as shown below.

The Shape Factor (SF) represents the degree of corneal asphericity or eccentricity. Shape factor can be used to determine whether the cornea is more oval or elliptical by assigning a factor or index to represent the shape of the surface. The higher the shape factor, the more keratoconus-like the cornea will be. The ranges for "normal," "borderline," and "abnormal" shape factors are shown below.

The Toric Corneal Measurement (TKM) is a value derived using elevation data from a best-fit toric reference surface as compared to the actual cornea. Two values are calculated at the apex of the flattest meridian and their mean determined. This is described as the mean value of apical curvature. By fitting the topography of the patient’s cornea to that of a best fit toric (using elevation data), all of the correctable sphere and cylinder can be accounted for in the topographical data. The ranges for "normal," "borderline," and "abnormal" TKM values are shown below.

Figures 21 and 22 illustrate a case of unilateral keratoconus. Note the differences in Pathfinder analysis of the keratoconic right eye (Figure 21) versus the non-keratoconic left eye (Figure 22).


Figure 21. The Pathfinder analysis of a patient with unilateral keratoconus. The right eye values (black arrows) are all in the red, indicating abnormal topographic findings characteristic of keratoconus.


Figure 22. The left eye of the same patient shows normal with-the-rule astigmatism with all three topographic indices in the normal yellow and green.


The diagnosis of keratoconus can be extremely difficult and one in which a number of anatomical and optical findings must be considered together. It is, therefore, important to remember that despite the sophistication and accuracy of modern keratoconus detection modules, they can serve only as another tool to aid in the diagnosis. This is because a number of conditions can topographically mimic keratoconus. These include corneal trauma, post herpes simplex infection, and contact lens wear. Therefore, many clinicians agree that the diagnosis of keratoconus should not be made solely based on the topographic findings, but instead should be based on combined clinical findings that include positive topographic data as well as optical and slit lamp findings.





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