OVERVIEW
We all routinely see patients with variable prescriptions, poor end point acuity even when the greatest care is taken with the refraction.

Typically a casual examination of the eye reveals very little evidence of problems and in most cases the early signs of the condition are completely over looked.

The astute clinician will however suspect irregular astigmatism, use the keratometer or more recently introduced corneal topography systems to confirm his suspicions and the diagnosis is easily made. This paper deals with the latest information available on anterior keratoconus.

DEFINITION
Keratoconus is defined as a disorder characterised by progressive corneal steepening, most typically inferior to the center of the cornea, with eventual corneal thinning, induced myopia, and both regular and irregular astigmatism.

EPIDEMIOLOGY
The prevalence of keratoconus in the general population appears to be relatively high and is reported to be between 50 - 230 per 100 000 or 1 in 2000 (Rabinowitz, Davis) or 54.5 per 100 000 (Minnesota Study).^{1, 2, 3}

The disease has no racial predilection,2 although it is my experience that it is more common in certain population groups in South Africa. More males are affected than females with a ratio (male to female) 1.58:1.⁴

Prior to the advent of corneal topography it was reported that the disease was 85.6% bilateral, with the regular use of corneal topography however the disease was found to be bilateral, but asymmetric in 96% of all cases.^{5, 6}

According to the CLEK study the average age of diagnosis was 27 years although the disease has its onset at puberty.⁶

ETIOLOGY
The most common presentation of keratoconus is as an isolated sporadic disorder with no other associated systemic or ocular disease detectable on clinical evaluation.

However the following should be considered: The inheritance pattern of keratoconus is defined incompletely still. However, Rabinowitz et al. suggests that chromosome 21 may be the location of the defective gene in keratoconus. Chromosome 21 is also the location of the collagen VI gene which is commonly found in the cornea.^{1, 2} Using Corneal Topography to access' family members, pedigrees have been analysed. These studies show corneal changes consistent with keratoconus in some family members which would indicate an autosomal dominant pattern of inheritance.² Studies by Hallerman, Hammerstein, Macsai and Tufts show that the percentage of patients with a blood relative with keratoconus varied from 2.6% to 8.2%.^{1, 2} While findings are consistent with autosomal dominant inheritance, incomplete penetrance and variable expressivity is present, therefore children of parents with keratoconus have less than a 1 in 10 chance of having the disease.¹

Systemic conditions are also frequently associated with Keratoconus and the most common are:^{2, 3, 6, 7}

• Down syndrome: Incidence from 0.5 - 15% (10 to 300 x more common than in the general population).2 possibly associated with eye rubbing due to blepharitis. Hydrops was also found more commonly.
• Leber's congenital amaurosis: Up to 30% of patients older than 15 years. Possibly due to ocular digital sign (eye rubbing).
• Connective tissue disorders: Advanced conus was associated with mitrial valve prolapsed (58% as to 7% in patients without conus).2
• Ehlers - Danlos syndrome, and osteogenesis imperfecta association not clear.
• Atopic disease
  Hay fever, asthma, eczema and food allergies are common in conus. The CLEK study reported a 35% incidence.6

Other associated systemic disorders are summarised in table 1:^1,2,3,6,7
Table 1

Eye rubbing among conus patients is common with percentages ranging from 66% Copeman, 73% Karsas and 80%
Rabinowitz.^{1, 2, 3, 6, 7} Ridley postulates that the cornea already weakened by inflammation can develop thinning and protrusion with mechanical trauma (rubbing). The cause-and-effect relationship however has not been established. Hormonal changes have been implicated as a possible cause due to the fact that the onset is often at puberty and the disease occasionally develop and progress during pregnancy. However no direct evidence of a cause-and-effect relationship exists.

Szczotka reported that constant rigid lens movement and hypoxia from PMMA lens wear may cause corneal tissue changes common to keratoconus.

89% of patients developing keratoconus after contact lens wear used PMMA lenses for an average of 12.2 years and 15.3 hours of wear per day.^{2, 7, 8}

It is important to remember that early keratoconus presents typically with mild myopic astigmatism and clinically normal - looking corneas, best corrected with RGP lenses. One can then ask, what came first the keratoconus or the contact lenses?
Given the high incidence of Keratoconus in the general population the associations may be co-incidental.

Figure 1 Vogt's striae and scarring

Figure 2 Fleischer's ring

Figure 3 Photokeratoscopy of moderate keratoconic cornea

Figure 4 Corneal topography of moderate keratoconic cornea in fig. 3

Figure 5 Acute Hydrops

OCULAR MANIFESTATIONS
The ocular manifestation of keratoconus is limited to the cornea.^{1, 2, 3, 6, 7} They include steepening of the cornea, especially inferiorly, thinning of the corneal apex, clearing zones in the region of Bowman's layer, prominent corneal nerves, scaring at the level of Bowman' layer, and deep stromal stress lines that clear when pressure is applies to the globe (Vogt's striae, fig 1).
An iron deposition ring accumulates in the epithelium at the base of the cone, easily appreciated with oblique cobalt blue illumination. (Fleischer ring, fig 2).

The steepening of the cornea leads to clinical signs, which include3,7 protrusion of the lower lid on down gaze (Munson's sign), focusing of a light beam shown from across the cornea in an arrowhead pattern at the nasal limbus (Rizutti sign), reduced corneal sensation in the inferior cornea, posterior crocodile shagreen, and a dark reflex in the area of the cone with ophtalmoscopy, retinoscopy (Charleaux's sign). Photo keratoscopy shows a compression of the mires interotemporally, centrally or inferiorly (Fig. 3).

Computerised video keratography has recently been employed to confirm the diagnosis of keratoconus. Rabinowitz suggested that the diagnosis can be made on the basis of observation of the following.^2,3,9

• Keratometry values higher than 47.20D (Corneal Curvature).
• Steepening of the inferior cornea compared to the superior cornea of more than 1.2D (Corneal slope or Eccentricity).
• Skewing of the radial axis of astigmatism by greater than 21¡ (Corneal Shape)
• Increased area of corneal power surrounded by concentric areas of decreasing power. (Corneal Regularity)

He reported a 98% Sensitivity and 99.5% Specificity in diagnosis when using the above system to evaluate the topography maps. (Fig. 4)

According to Mc Mahon the most common ocular signs were:2,6 Fleischer's ring found in 98% of patients.
Vogt striae found in 60% of patients.
Corneal scarring found in 52% of patients.

SUBJECTIVE SYMPTOMS:1

• Deteriorating monocular acuity.
• Frequent changes in refraction.
• Monocular diplopia or ghosting.
• Squinting or pressure on the globe improves acuity.
• High myopia and astigmatism with poor best corrected vision.
• Glare at night

PATHOLOGY
The triad of classical histo-pathology features found in keratoconus include, thinning of the corneal stroma, breaks in Bowman's layer, and deposition of iron in the epithelium. However, every layer and tissue of the cornea can be involved depending on the stage of the disease.

Features noted in the epithelium include degeneration of the basal cells, breaks accompanied by down growth of epithelium into Bowman's layer and accumulation of Ferritin (Fleisher's ring) and other particles within and between basal epithelial cells at the base of the cone.^2,3,7

Features noted in Bowman's layer and the epithelial basement membrane include fragmentation and fibrillation (underlying normal stromal collagen fills breaks) in the area of the cone, interruptions of Bowman's layer are common, and activated keratocytes and scar tissue can be found in these areas.^2,3,7
Features noted in the stroma are compaction and loss of arrangement of fibrils in the anterior stroma, decrease in the number of collagen lamellae, and the presence of normal and degenerating fibroblasts and keratocytes. However, the hexagonal arrangement of the fibrils is not changed, and the interfibrillary distance does not increase to the point that clarity is lost.^2,3,7

Descemet's membrane is rarely affected except for breaks seen in acute hydrops.^2,3,7

The endothelium is usually normal, although some abnormalities have been reported including; intracellular dark structures, pleomorphism, and elongation of the cells with their long axis toward the cone.²

HYDROPS
In some patients with keratoconus, acute rupture of Descemet's membrane may occur resulting in an over hydration of the cornea and an accumulation of vacuoles of fluid in the stroma. The overlaying epithelium may become edematous and occasionally fluid may leak through the epithelium. (Fig. 5) The ruptured Descemet's membrane curls in upon itself and over time the endothelial cells spread over the posterior stromal defect to lay down a new Descemet's membrane recompensating the cornea, 3 - 4 months after the acute event. Subsequent to this the corneal steepness may reduce.⁷

The patient will experience pain, foreign body sensation, hyperemia and sudden vision loss which will resolve spontaneously. Acute hydrops is self limiting, but can be treated initially with cycloplegics, steroids, or non steroidal anti inflammatory agents, 5% sodium chloride and in rare instances with bandage contact lenses.

CLASSIFICATION^2,3,7,9
Keratoconus can be classified in three ways:
1.Cone type and position.

a. Central or nipple type cone located centrally. (Fig. 6)

Figure 6 Severe nipple cone

b.    Oval or sagging cone located inferiorly or  inferotemporaly. (Fig. 7)

Figure 7 Oval or sagging cone


c.    Globus, more than 75% of the cornea is affected
These cones can be distinguished on slit-lamp examination or evaluation of the anterior corneal topography.

2. Corneal curvature.

3. Corneal thickness in microns.

Figure 8 Flat fitting lens.

Figure 9 Corneal scarring.

Figure 10 Optical section, scarring.

PROGRESSION
One of the most common questions asked by both patients and practitioners is what the patient with keratoconus can expect with regard to his/her quality of vision and the need for surgical correction now or in the future.

Most of the data available is anecdotal and based on clinical impressions; however one terminal measure of progression is whether or not patients receive a penetrating keratoplasty.¹
The CLEK study reports that 305 of 2400 eyes (13%) had undergone surgery with the mean age at surgery being 34 years and the mean number of years after diagnosis to surgery being 7 years.^1,6 Analysis of the data suggests the eyes at risk for surgery are in patients who:1

• Were diagnosed at a younger age
• Have longer contact lens wearing history
• Have steeper keratometry values
• Have the worst corrected acuity
• More likely to have scarring, Vogt's striae and Fleischer's ring.

Although progression may be more rapid in the patient diagnosed at a younger age, most patients plateau after a period of 7 - 10 years.^1,2,3,6,7,10

An area of tremendous interest is whether or not the mainstay of optical correction, rigid contact lenses, has an influence on the progression of keratoconus. As mentioned earlier some authors suggest that rigid lenses facilitate the development of keratoconus, while others have advocated their use as a way to delay or halt the progression.^1,2,3,6,7

The current data suggests the following with regard to the influence of rigid gas permeable lenses on the natural history of keratoconus:¹

Some rigid contact lens wearers, who do not have the definitive slit-lamp signs of keratoconus, develop corneal topography shapes indistinguishable from keratoconus.

• Many keratoconus patients who are also rigid lens wearers develop lens induced warpage.
• Keratoconus patients who use rigid contact lenses may have flatter corneal curves than those who do not wear lenses.
• Keratoconus patients who wear excessively steep or flat lenses are more likely to have altered corneal shapes.
• Excessively flat lenses may promote the development of anterior stromal scarring. (Fig.8, 9 ,10)

MANAGEMENT
The mainstay management for keratoconus includes spectacles and contact lenses. As stated previously 13 - 20% of keratoconus patients will require Penetrating Keratoplasty on one or both eyes during their lifetime.^1,2,3,6,7 Newer surgical techniques include the use of Intac's and will be briefly discussed later.

Optimal management of the keratoconus patient has tremendous individual patient and practitioner variation and often the inexperienced clinician associates the keratoconus patient only with rigid gas permeable lenses.
I use the following nomogram to manage keratoconus patients.

Keratoconus management nomogram 1

In general the, early keratoconus patient, if detected, may be managed like the typical refractive error patient with spectacles, spherical rigid or soft lenses and soft toric lenses. Once vision is found to be inadequate, then rigid lens alternatives should be considered to provide the best visual outcome.

The next article in the series will be dedicated to contact lens management of the keratoconus patient.

SURGICAL MANAGEMENT
Many keratoconus patients perceive corneal surgery as an opportunity to be free from the troubles of their contact lenses, we as their care givers must educate them, regarding this option for visual rehabilitation!

The primary indications for surgery are:^1,2,3,7

• Loss of functional vision, corrected acuity less than  20/40 (6/12).
• Intolerance to contact lens wear.
• Large areas of corneal thinning.
• Very decentered cones.
• Neovascularization due to contact lens wear.
• Frequent abrasions or recurring corneal infections.
• Scarring in the visual axis.

Figure 11

Corneas in keratoconus almost never perforate; therefore advanced thinning is not necessarily an indication for surgery.² When acute hydrops resolves the resultant scarring may flatten the cornea. Frequently the scar is outside the visual axis and the patient can be effectively helped with contact lenses or spectacles, therefore acute hydrops is not necessarily on indication for surgery.

Penetrating keratoplasty. (Fig. 11)
The most successful surgical procedure for keratoconus is penetrating keratoplasty with a success rate of 93 - 96% due to the avascular nature of the cornea and post-operative graft clarity.^1,2,3 However, post-operative refractive error, anisometropia and irregular astigmatism often necessitate the use of spectacles and or contact lenses following surgery.

Post-operative myopia and astigmatism can be corrected with a combination of relaxing incisions and compression sutures using corneal topography as a guide, or more recently by using LASIK (laser in situ keratomileusis).

Complications after penetrating keratoplasty are rare but include:^{2, 3 ,7}

1. Rejection, more common in larger grafts. Graft rejection can be divided anatomically into three categories:³
   • Epithelial rejection - May be recognised by observation of an epithelial line, which represents the replacement of the donor epithelium by that of the recipient.³
   • Sub-epithelial rejection - Multiple sub epithelial infiltrates limited to the corneal graft may be observed.³
   • Endothelial rejection - Most severe type characterised by keratic precipitates, iritis and corneal edema. A Khodadoust line may be seen, which represents the advancing front of the host immunologic and inflammatory cells against a receding front of donor endothelium. Alldredge and Krachmer reported an overall incidence of endothelial graft rejection of 21%.³
2. Urrets - Zavalia Syndrome fixed dilated pupil after kerato plasty for keratoconus due to iris ischemia.^2,3,7
3. Recurrence of keratoconus, although this is extremely rare.
4. Wound leak, glaucoma, endophthalmitis, and persistent epithelial defects are early complications.³
5. Post-operative irregular astigmatism and myopia. Approximately 60% of patients will require contact lens fitting after keratoplasty.7

Despite the proved outcome with penetrating keratoplasty, it is still the author's belief that contact lenses should be the treatment of choice for most patients of who have keratoconus.

Smiddy found that 69% of patients referred for penetrating keratoplasty could be successfully refitted with special contact lens designs.

Lamellar keratoplasty and Epikeratoplasty.
Lamellar keratoplasty is a procedure in which a partial thickness graft of donor tissue is used to provide tectonic stability and or optical improvement. The transplanted tissue does not include corneal endothelium, and therefore the donor tissue is obtained more easily from older eyes and also endothelium rejection is avoided.^3,7

It is an extra ocular procedure, therefore has a lower risk of endophthalmitis. The healing period is also shorter than for penetrating keratoplasty.

The disadvantages include technical difficulty and limited visual outcome as a result of possible opacification and vascularisation of the donor - recipient interface. Perforation of recipient cornea, persistent epithelial defects, and inflammatory necrosis of the graft, graft melting, infection, astigmatism, and allograft rejection are other complications.^3,2

Epikeratoplasty, or outlay lamellar keratoplasty is a surgical procedure in which a lens made from human corneal tissue is sutured on to the anterior surface of the cornea. The tissue lens consists of Bowman's layer and anterior stroma of a donor cornea that has been frozen and lathed to a uniform thickness of 0.30mm.^3,7

When used in keratoconus it is designed to re-enforce the cornea and flatten the cone in patients with no central or para-central scarring within 1mm of the visual axis, and cones less than 60D. An average of 9.0D of corneal flattening is obtained, and approximately 80% of patients obtain 20/40 (6/12) or better acuity. The main advantages is that it is a extra-ocular procedure, there is no risk of rejection, and the fact that it is a technically simpler procedure than lamellar keratoplasty.⁷ Complications include persistent epithelial defects, interface opacification, scarring and opacification, infections, keratitis, sterile ulceration of the lenticels and recipient stroma, steepened recipient cornea and endothelial changes.³

Figure 12

Persistent irregular astigmatism and residual myopia can also be problematic.

Intac's (Fig. 12)
Intrastromal ring implants have also recently been used to surgically treat early and moderate keratoconus with varying success.

Advantages include reversible nature of the procedure and short post-operative time for visual rehabilitation. However the procedure carries the risk of infection, abnormal wound healing and induced irregular astigmatism.³

The procedure however holds promise for the future.

SUMMARY
The treatment of keratoconus falls within the scope of the optometrist and is one of the conditions that lends itself to effective co-management with ophthalmology. However, those of us with some keratoconus experience know, every keratoconic cornea has its own individual personality, making many patients schizophrenic - ocularly speaking.

The time, expense, fitting skills and patience that this work requires may seem to be less than adequately compensated for and occasionally abused by the frustrated patient. The rewards however, are well worth the effort.

REFERENCES

1. Davis LJ. Keratoconus: Current understanding of diagnosis and management. Clin Eye Vis Care9(I): 13-22, 1997.
2. Rabinowitz YS. Keratoconus. Survey of ophthalmology, vol 42, number 4, Jan-Feb 1998.
3. Yanoff M, Duker JS. Opthalmology, Mosby 1999. Chapters 5 (5.7) and 5 (12.1- 12.18).
4. Kenny CM, Brown D. Keratoconus research review. www.csmc.edu/nkcf/review.html
5. Maguire LJ, Lowry JC. Identifying progression of sub-clinical keratoconus by serial topography analysis. Am J Ophthalmol 1991; 112(7): 41-45.
6. Zadnik K et. al. Biomicroscopic signs and disease severity in keratoconus. Cornea, vol. 15, No 2, 1996.
7. Arffa RC. Grayson's diseases of the cornea. Third edition, Mosby 1991, Chapter 17 p401-409.
8. Szczotka LB. PMMA lens wear a probable cause of keratoconus. November 1999.
   www.contactlensspectrum.com/newarchive/199.../1199015.ht
9. Schanzlin DJ, Robin JB. Corneal topography, measuring and modifying the cornea. Springer-Verlag. Chapter 7.
10. Schendowich B. Helping the keratoconus patient cope. Contact lens spectrum/ October 1999, 29-34.