Keratoconus

Author:
Laura L Wayman, MD
Section Editor:
Jonathan Trobe, MD
Deputy Editor:
Jane Givens, MD
Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2020. | This topic last updated: May 12, 2020.

INTRODUCTION Keratoconus is a noninflammatory disorder of the cornea

of unknown etiology. It is characterized by progressive thinning and cone-shaped

protrusion of the cornea leading to visual impairment (picture 1). Patients may
present with blurry vision or a sudden decrease in visual acuity. Corrective lenses
may be difficult to fit and require frequent changes due to progressive myopia and
irregular astigmatism. Visual impairment can be managed initially with corrective
lenses but may require corneal cross-linking to prevent disease progression or
penetrating keratoplasty in more advanced disease.

EPIDEMIOLOGY Patients present at puberty or early adulthood. There are

a wide range of prevalences reported in the general population, ranging from 50 to

230 per 100,000 [1-3]. There is no difference in incidence and prevalence between
genders [1-5]. Some evidence suggests a higher incidence in Asians from the Indian
subcontinent [6,7]. Another study did not support the association between Asians
and keratoconus. However, the study did find that blacks and Latinos have
approximately 50 percent higher odds of having keratoconus when compared with
whites [8].

RISK FACTORS

●Systemic disorders – Several studies have linked keratoconus to systemic

disorders including Down syndrome, Ehlers-Danlos syndrome, and
osteogenesis imperfecta [8,9]. None have been able to prove a direct cause-
and-effect relationship.
●Environment – Atopic disease, asthma, and hay fever have been associated
with keratoconus; however, not all studies have found an association [3,9].
●Eye-rubbing – Reports based on clinical observation have implicated eye
rubbing as a risk factor for keratoconus [9].
●Contact lens use – Contact lens use has been implicated in the development
of keratoconus; however, there is little evidence to support the association
[10,11].
●Family history – The number of pairs of identical twins with the disease
suggest that a genetic abnormality may be one of several factors involved in the
etiology of this disorder [10,11]. A family history of keratoconus has been
 reported in 6 to 8 percent of cases, but the definitive role of inheritance patterns
has not been determined. This disorder has weak penetrance and significant
variability of expression [12].

PATHOPHYSIOLOGY Keratoconus is a noninflammatory disorder of the

cornea of unknown etiology. Keratoconic corneas have lower collagen content

compared with normal corneas [5]. The corneas of patients with keratoconus
demonstrate abnormalities in their molecular structure, but a specific biochemical
disease pattern has not been established. Similar molecular changes are seen in
eyes with corneal scars, suggesting that these changes could be secondary to the
disease sequela [13]. The corneal thinning seen in keratoconus is possibly the result
of a multifactorial degradation process that results in the loss of structural elements
of the cornea. The cause of this thinning is not clear [3].

CLINICAL FEATURES Patients present at puberty or early adulthood

with blurry vision or a sudden decrease in visual acuity. Symptoms progress until the
fourth decade. While vision is initially corrected by spectacles, as the disease
progresses, patients may develop irregular astigmatism and require contact lenses
for refractive correction.

Clinical features which may more specifically suggest the diagnosis include the
following:

●Asymmetric visual complaints – Although keratoconus is usually a bilateral

disease, patients may present with asymmetric symptoms as one eye may be
much more severely affected than the other. One study in 64 patients reported
that 41 percent had unilateral disease at the time of diagnosis [2].
●Difficulty with visual correction – As the disease progresses, patients
experience difficulties with their spectacle correction and contact lens fitting.
Patients may require frequent changes in spectacles due to progressive myopia
and astigmatism.
●Munson's sign – In advanced keratoconus, patients may have a v-shaped
indentation of the lower eyelid on downgaze caused by a large protuberant
cone.
●Corneal hydrops – As keratoconus progresses, some patients can present
with photophobia and a sudden painful drop in visual acuity that is due to
corneal hydrops. The symptoms are caused by the sudden onset of severe
corneal edema caused by tears in the Descemet membrane and loss of
functionality of the endothelium as a result.
Corneal hydrops may occur in about 3 percent of patients with keratoconus. The
mean age of onset of corneal hydrops is 25 years of age and is thought to be
more common in men [14]. The treatment of corneal hydrops is discussed
below. (See 'Corneal hydrops treatment' below.)
 DIAGNOSIS Although no one finding can definitely establish the presence

of keratoconus, ophthalmologists are able to diagnose it by history and clinical exam.

The signs and symptoms vary depending on the stage of the disorder.

Early in the disease, the ophthalmologist may suspect keratoconus because of

difficulty correcting a patient’s vision to 20/20 visual acuity. The cornea may appear
normal on slit lamp examination, but other methods may aid in the diagnosis of
keratoconus. For example, keratometry may show distorted mires centrally or
inferiorly [2,3]. Newer technologies, such as corneal topography, can also assist in
making the diagnosis and evaluating disease progression [15].

As the disease progresses, slit lamp findings become common and include (see "Slit
lamp examination"):

●Fleisher ring – Brown-colored staining around the base of the cone is a subtle
early sign and can be noted even when the cone is minimally elevated. It is
composed of iron deposited within the epithelium by the tear film. The iron flows
with the tear film around the base of the cone. The ring is best seen with the
cobalt blue filter on the slit lamp.
●Vogt striae – Vogt striae are vertical stress lines in the thinnest part of the
cornea at the level of the posterior stroma and Descemet membrane. Unlike
Haab striae and folds secondary to corneal edema, Vogt striae disappear when
gentle pressure is applied to the cornea.
●Central and inferior paracentral corneal thinning – Central and inferior
paracentral corneal thinning, along with mild cone formation and protrusion, is
an early manifestation of keratoconus.
●Corneal scarring – Corneal scarring is the result of spontaneous breaks in
Bowman's layer as the cornea thins (picture 2). It is estimated that 20 percent of
patients with keratoconus will have corneal scarring [16].

Ophthalmologists may use other technologies in the diagnosis and evaluation of

keratoconus:

●Retinoscopy – The scissoring reflex is an early sign of developing

keratoconus seen on retinoscopy. The ophthalmologist may see two light bands
moving towards and then away from each other, similar to the action seen with
scissors. The reflex is due to irregular astigmatism.
●Keratometry – Keratometry may demonstrate irregular mires and progressive
corneal steepening [1].
●Corneal topography – The introduction of corneal topography has helped in
the identification of subtle presentations, which can lead to an earlier diagnosis.
Major topographic patterns found in keratoconus include asymmetric bowtie,
with or without inferior steepening, and skewed radial axes [17]. However, once
the diagnosis is made, serially corneal topography is of little value in following
patients.
 DIFFERENTIAL DIAGNOSIS Keratoconus is distinguished from

progressive myopia by the clinical examination findings discussed above.

The ophthalmologist may also consider other ectatic disorders of the cornea in the
differential diagnosis of keratoconus. These include keratoglobus and pellucid
marginal degeneration [18].

MANAGEMENT Corneal collagen cross-linking is recommended for the

management of keratoconus. It has been shown to slow the progression by

strengthening collagen fibers. In patients with stable disease, advanced ectatic
disease (cornea is too thin), or severe scarring, correction of visual impairment may
require spectacles, contact lenses, or surgical interventions.

Collagen cross-linking — Collagen cross-linking is a procedure that uses riboflavin

drops, ultraviolet light, and a photosensitizer to strengthen bonds in the cornea.

In a multicenter trial comparing collagen cross-linking to riboflavin drops alone in

over 200 patients with progressive keratoconus, improvements in the maximum
keratometry value, as well as in corrected and uncorrected distance visual acuity
were noted in the treatment group at one year [19]. Transient or permanent corneal
haze was the most frequently reported adverse event. Earlier trials and cohort
studies of collagen cross-linking demonstrated flattening of the cornea and
improvement in visual, topographic, and wavefront parameters that were maintained
for up to seven years [20-22].

Collagen cross-linking is generally not performed in patients with active or history of

herpes simplex virus (HSV) keratitis, thin corneas, or corneal hydrops.

Correction of vision
●Spectacles – In the early stages, the treatment of choice is spectacle
correction. These are used as long as the visual acuity allows the patient to
function.
●Contact lens – As the disease progresses and irregular astigmatism
increases, contact lenses may become necessary to maximize the patient’s
visual acuity. A large portion of patients with keratoconus can be managed
conservatively with contact lenses for an extended period of time [23].
(See "Overview of contact lenses".)
Rigid gas-permeable lenses are the most common contact lens used in
keratoconus. The contact lens smooth out the irregularity of the cornea with its
rigid, regular optical surface. In some patients, particularly if the scarring is
irregular or elevated, rigid gas-permeable contact lens wear can become
intolerable. If significant corneal irregularity due to scarring, surface nodules, or
severe conical shape is present, contact lens correction will likely fail.
●Surgical interventions – Intrastromal corneal ring segments were approved
by the US Food and Drug Administration (FDA) in 2004 for the management of
 keratoconus. This technique has also been studied in combination with collagen
cross-linking [24]. These thin, semicircular plastic inserts are implanted into the
mid-corneal layers to flatten the cornea. The goal is to improve the patient’s
visual acuity by reducing the amount of astigmatism. Several authors have
reported flattening of the cornea and significant improvement of refractive errors
[25,26]. However, this treatment is not useful in patients with more advanced
vision loss.
Keratectomy is uncommonly used in the treatment of corneal scars and nodules
to improve contact lens tolerance. However, recurrence is possible and can
stimulate progression [27,28].
●Keratoplasty (corneal transplantation) – Keratoplasty is the procedure of
choice when contact lenses are no longer helpful. Approximately 10 to 15
percent of patients with keratoconus will require keratoplasty; penetrating
keratoplasty (full thickness corneal transplant) is the most commonly used
procedure [29,30]. This procedure has a success rate of greater than 90 percent
in patients with keratoconus [31]. Studies have reported visual acuity of 20/40 or
better in 80 to 90 percent of patients [31-33]. Of those patients, 15 percent
obtain that visual acuity without correction, 40 percent with spectacle correction,
and 26 percent with contact lenses. Graft rejection has been reported in 20 to 35
percent of cases in the first 12 months after surgery. It is associated with loose
sutures, trauma, and large grafts [31]. The majority of cases are treated
successfully with corticosteroids. A more common complication of penetrating
keratoplasty is astigmatism. Treatment options for astigmatism include contact
lens correction, refractive surgery, relaxing incisions, wedge resection, and
compressive sutures.
Deep anterior lamellar keratoplasty (partial thickness corneal transplant) is
another option for keratoplasty that may be used in the treatment of keratoconus
[30,34]. It is used infrequently in the United States.

Corneal hydrops treatment — Corneal hydrops generally resolves without

intervention over two to four months, although the patient will experience discomfort
and compromised vision during that time [4,14,35]. As the tears in Descemet’s
membrane heal, endothelial function returns and the corneal edema gradually
lessens.

Evidence about effective treatment is lacking [14]. Treatments include pressure

patching and bandage contact lenses as well as topical hyperosmotics, cycloplegics,
and steroids in an attempt to decrease edema, pain, and inflammation. Intracameral
perfluoropropane gas injection has been found to decrease the time to resolution of
hydrops but does not change the outcome in terms of visual acuity or need for
corneal transplantation. Corneal perforation is very rare. Keratoplasty is not indicated
in the acute stage.

After an episode of corneal hydrops, the cornea is left with a scar [3,9].
Paradoxically, the severity of the cone may be reduced as the cornea flattens. This
may result in reduced and more manageable astigmatism. Eventually, however,
patients may require keratoplasty because of corneal scarring as a result of hydrops.
 PROGNOSIS Keratoconus is a progressive condition. In a 2019 meta-

analysis of the natural history of keratoconus, factors associated with a higher

likelihood of progression included younger age and keratometry measurements
steeper than 55 diopters at presentation [36]. Other factors associated with
progression are corneal scaring and worsening visual acuity [16,29]. One study
reported a 12 percent rate of keratoplasty over eight years of follow-up [29].

SUMMARY AND RECOMMENDATIONS

●Keratoconus is a noninflammatory disorder of the cornea of unknown etiology.

It is characterized by progressive thinning and cone-shaped protrusion of the
cornea leading to visual impairment. (See 'Pathophysiology' above.)
●Keratoconus is more common in those with a family history of the disorder. It
has also been found to be associated with certain systemic disorders. Contact
lens use is not clearly a risk factor. Some observations implicate eye rubbing.
(See 'Risk factors' above.)
●Patients present at puberty or early adulthood with vision impairment that may
be asymmetric. Vision impairment progresses until the fourth decade. Difficulty
with vision correction may be the first indication of this disorder. (See 'Clinical
features' above.)
●Corneal hydrops may be seen in advanced keratoconus. It is caused by
sudden onset of severe corneal edema that can lead to a sudden, painful drop
in visual acuity. This typically resolves over a few months. While there is limited
evidence for effective treatments, symptomatic therapies are often tried.
(See 'Clinical features' above and 'Corneal hydrops treatment' above.)
●Corneal collagen cross-linking is suggested for the management of
keratoconus (Grade 2B). It has been shown to slow the progression by
strengthening collagen fibers. In some patients with keratoconus, correction of
visual impairment may also require spectacles, contact lenses, or surgical
interventions. (See 'Management' above.)