Keratoconus 

Updated: Oct 17, 2018
Author: Karen K Yeung, OD, FAAO; Chief Editor: Hampton Roy, Sr, MD 

Overview

Practice Essentials

Keratoconus (KC) is a progressive, noninflammatory, bilateral (but usually asymmetric) ectatic corneal disease, characterized by paraxial stromal thinning and weakening that leads to corneal surface distortion. Visual loss occurs primarily from irregular astigmatism and myopia, and secondarily from corneal scarring. See the image below.

An optic section of a keratoconic cornea shows cor An optic section of a keratoconic cornea shows corneal thinning. Vogt striae and some scarring can also be seen centrally; superiorly, a small (brown) section of the Fleischer ring is noted.
The fluorescein pattern of a rather flat-fitted ri The fluorescein pattern of a rather flat-fitted rigid contact lens on an advanced keratoconic cornea.

Signs and symptoms

Patients with keratoconus may report the following:

  • Distortion
  • Glare/flare
  • Monocular diplopia or ghost images
  • Multiple unsatisfactory attempts to obtain optimum spectacle correction
  • Itchy eyes

Keratoconus is differentiated into mild, moderate, and advanced cases.

Characteristics of mild keratoconus may include the following:

  • Absent or minimal external and corneal signs
  • Moderate-to-high myopia with oblique astigmatism on refraction
  • Irregular astigmatic keratometry values
  • Corneal inferior steepening, central corneal astigmatic steepening, or bilateral temporal steepening on corneal topography or tomography

Characteristics of moderate keratoconus may include the following:

  • Presence of one or more corneal signs of keratoconus (eg, enhanced appearance of corneal nerves, Vogt striae, Fleischer ring, corneal scarring)
  • Superficial corneal scarring (fibular, nebular, or nodular)
  • Deep stromal scarring
  • Scarring at the level of the Descemet membrane resembling posterior polymorphous corneal dystrophy
  • Paraxial stromal thinning
  • Keratometry values of 45-52 diopters (D)
  • “Scissoring” or the oil drop sign
  • Munson sign

Characteristics of advanced keratoconus may include the following:

  • Keratometry values greater than 52 D
  • Enhancement of all corneal signs, symptoms, and visual loss/distortion
  • Vogt striae; Fleischer ring and/or scarring
  • Acute corneal hydrops

See Presentation for more detail.

Diagnosis

No laboratory workup is necessary.

Diagnostic measures that may yield evidence of keratoconus include the following:

  • Refraction (including retinoscopy)
  • Slit-lamp biomicroscopy
  • Corneal topography
  • Corneal tomography

See Workup for more detail.

Management

Nonsurgical treatment measures include the following:

  • Rigid contact lenses or scleral lenses (mainstay of vision therapy): Patients with early keratoconus may successfully use spectacles or spherical/toric soft contact lenses. Those with moderate-to-advanced keratoconus almost always require rigid contact lenses or scleral contact lenses.
  • Corneal collagen cross-linking

Although no direct pharmacologic management is available, the following agents may be useful as adjunctive therapy for complications that occur concurrently with contact lens wear and atopy, which is common with keratoconus:

  • Combination topical antihistamine/mast cell stabilizer
  • Antihistamines
  • Mast cell–stabilizing topical medications
  • Ophthalmic cyclosporine
  • Steroid drops
  • Nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Hyperosmotic agents
  • Topical antibiotics

Surgical options include the following:

  • Collagen cross-linking (CXL)
  • Superficial keratectomy
  • Excimer laser phototherapeutic keratectomy
  • Implantation of intrastromal corneal rings (ICRS)
  • Bowman layer transplantation
  • Deep anterior lamellar keratoplasty (DALK)
  • Penetrating keratoplasty (PKP)

See Treatment and Medication for more detail.

Background

Keratoconus is a progressive, noninflammatory, bilateral (but usually asymmetric) ectatic corneal disease, characterized by paraxial stromal thinning and weakening that leads to corneal distortion. Visual loss occurs primarily from irregular astigmatism and myopia, and secondarily from corneal scarring.

Pathophysiology

All layers of the cornea are believed to be affected by keratoconus. Characteristic structural changes include epithelial basement membrane fragmentation and scarring, breaks in the anterior limiting lamina (ie, Bowman membrane), and axial stromal thinning and scarring. Deposition of iron in the basal epithelial cells forms the Fleischer rings. Breaks and folds close to the Descemet membrane form commonly seen striae and acute hydrops (although the latter are rare).

The literature on keratoconus is large and contradictory regarding the roles of disruption of collagen fibers, lamellae, and proteoglycans. Keratoconic corneas have been shown to have altered antioxidant enzymes, accumulations of cytotoxic reactive oxygen/nitrogen species, activated caspase pathways, and mitochondrial DNA damage. Abnormal oxidative stress-related properties have been found in keratoconic corneal cells. Oxidative stress elements can induce activation of degradative enzymes and degradation of tissue inhibitors of metal-low proteinases. Genomic deletion in the superoxide dismutase 1 (SOD1) gene has also been associated with the disease.[1, 2, 3, 4, 5]

Although usually believed to be noninflammatory, some data suggest an inflammatory component.[6]

Frequency

Reported prevalence in the general population varies (50-200 cases per 100,000 population), perhaps with differences in diagnostic criteria. It is commonly an isolated ocular condition but sometimes coexists with other ocular and systemic diseases.[7]

Commonly recognized ocular associations have included vernal keratoconjunctivitis, retinitis pigmentosa, and Leber congenital amaurosis. Systemic putative associations include many of the connective tissue disorders (eg, Ehlers-Danlos and Marfan syndromes), mitral valve prolapse, atopic dermatitis, and Down syndrome,[8] although none of these was found in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study.[9]

Particular risk factors include atopic history, especially ocular allergies, and perhaps either or both rigid contact lens wear, and vigorous eye rubbing.[10, 11]

Most keratoconus cases appear spontaneously, although approximately 14% of cases present with evidence of genetic transmission.[10]

The prevalence of keratoconus varies by ethnicity. Keratoconus is more common in blacks and Latinos than in whites, with odds ratios of 1.57 and 1.43, respectively. Data are conflicting on whether Asians are at a greater or lower risk for keratoconus.[12] The discrepancy could arise from the large diversity of Asians (eg, subcontinental Indian vs Middle Eastern vs Chinese) given that anecdotal reports suggest an increase in keratoconus prevalence in some parts of the world, Arabia, the Indian subcontinent, and New Zealand.[13]

Personal income, access to health care, and education levels have no known correlation with keratoconus.[12]

Sex

Keratoconus is six times more common in males than it is in females.[12]

Age

Keratoconus typically presents at puberty and progresses until the third and fourth decades of life, although it can occur or progress at any age. Keratoconus progresses at various rates but tends to progress more rapidly in young patients and stabilizes approximately 20 years after initial onset.[14]

Mortality/Morbidity

Because few elderly patients have been noted with keratoconus, many wonder if keratoconus is associated with a fatal disease. There are mixed results regarding whether keratoconus is associated with an increased mortality risk.[15, 16, 17]

Advanced keratoconus may rarely progress to corneal hydrops. Corneal hydrops are breaks in the Descemet layer that cause aqueous to enter the stroma, leading to central stromal edema and potentially secondary severe corneal scarring. Patients report sudden loss of vision and some ocular discomfort in one eye but usually not much pain or conjunctival injection. Acute treatment of hydrops is palliative; many corneas flatten secondary to hydrops, and both visual acuity and contact lens application may improve following such events. If secondary scarring is severe, corneal transplantation (PKP) may be warranted.

Corneal surgery is indicated when contact lenses are either no longer tolerated or can no longer correct vision to better than 20/40. The rate of patients with keratoconus requiring PKP has been decreasing, from 20% to 2.4%, because of improved contact lens designs and better surgical correction techniques, including CXL.[18] The need for PKP increases when optimal contact lens care is not available. Many patients still require contact lens care for optimum visions following PKP.

Prognosis

Most patients with keratoconus do well with rigid contact and scleral lens care.

About 10%-20% of patients with keratoconus eventually require corneal transplantation,[18] but this number is believed to increase if good contact lens care is unavailable.

Data suggest that this disease, although progressive, stabilizes after some time in most patients.

Patient Education

Patients with keratoconus and their family members may benefit from genetic counseling.

 

Presentation

History

Patients with keratoconus often report decreasing vision (distortions, glare/flare, and monocular diplopia or ghost images), with multiple unsatisfactory attempts in obtaining optimum spectacle correction.

Soft contact lenses and spectacles may initially give satisfactory vision, but vision tends to decline over time and requires rigid gas-permeable contact lenses for correction. Other contact lens options include piggyback lens systems (usually a gas-permeable lens over a soft, perhaps silicone hydrogel, lens), hybrid lenses (eg, Synergeyes TM) and, increasingly over the past decade, gas-permeable scleral lenses.[9, 19]

Physical

Keratoconus is differentiated into mild, moderate, and advanced disease, as well as by shape.

Mild keratoconus

External and corneal signs are often absent or minimal.

A history of multiple inadequate spectacle corrections of one or both eyes may be noted and may include oblique astigmatism on refraction as well as moderate-to-high myopia.

Irregularly astigmatic keratometry values (egg-shaped), not necessarily on the steep side of normal (approximately 45 D), are consistent with diagnosis.

Diagnosis can be confirmed with corneal topography or tomography, which may reveal inferior corneal steepening (approximately 80% of keratoconus cases), central corneal astigmatic steepening (approximately 15% of keratoconus cases), or even bilateral temporal steepening (extremely rare).

Corneal tomography shows paraxial corneal thinning.

Corneal sensitivity and tear secretion are decreased.[20]

Moderate keratoconus [10]

One or more corneal signs of keratoconus are often present, as follows:

  • Enhanced appearance of the corneal nerves is noted.
  • Approximately 40% of eyes in patients with moderate keratoconus develop Vogt striae (fine-stress lines) in the deep stroma.
  • Approximately 50% develop Fleischer ring, a deposition of iron in the basal epithelial cells in a (often partial) ring shape at the base of the conical protrusion.
  • Approximately 20% develop corneal scarring.

Superficial corneal scarring can be fibular, nebular or nodular.

Deep stromal scarring may occur, perhaps representing resolved mini-hydrops events.

Some patients show scarring at the level of the Descemet membrane (posterior limiting lamina), consistent in appearance with posterior polymorphous corneal dystrophy. This may be a posterior polymorphous corneal dystrophy variant.[21]

Paraxial (usually inferior to the pupil) stromal thinning may be appreciated.

Keratometry values typically increase to 45-52 D.

Distortion of the retinoscopy and direct ophthalmoscope red pupillary reflex may allow observation of "scissoring" or an inferior distortion termed the oil drop sign.

The Munson sign is noted when, upon downgaze, a "V" shape is visible in the cornea's profile against the lower lid margin. This is the accentuation of the conical shape of the modest to advanced keratoconus cornea.

Advanced keratoconus

Keratometry values are greater than 52 D.

Enhancement of all corneal signs, symptoms, and visual loss/distortion, including Vogt striae, Fleischer ring, and/or scarring, is present.

Acute corneal hydrops may occur.

Shape-based differentiation

Keratoconic eyes can also be divided by their shape.

Nipple cones have a diameter of 5 mm or less and are located in the center or slightly below the center of the cornea.

Oval cones are larger in diameter and reside inferonasally or inferotemporally to the center of the cornea.

Globus cones involve approximately 75% of the cornea and are the least common.

Causes

Although not definitively identified, genetic inheritance, systemic and ocular associations, eye rubbing, atopy and specifically ocular allergies, and contact lens wear are proposed risk factors.[22, 23]

Several reports suggest, perhaps coincidentally, associations with keratoconus and other corneal dystrophies.

Complications

Advanced keratoconus rarely progresses to acute corneal hydrops (acute keratoconus), wherein breaks occur in the Descemet layer that lead to central stromal edema and secondary severe corneal scarring.

Patients report a sudden loss of vision and some ocular discomfort or pain in one eye but usually not much conjunctival injection.

Acute treatment of hydrops is palliative; many corneas flatten secondary to hydrops, and both visual acuity and contact lens application may rarely improve following such events.

If secondary scarring is severe and central, corneal transplantation (ie, PKP) may be warranted.

Patients with keratoconus develop all complications of contact lens wear, especially abrasion[24] and giant papillary conjunctivitis. Contact lens–related secondary giant papillary conjunctivitis may be treated with topical mast cell stabilizers, antihistamine, and, occasionally, steroid drops.

 

DDx

Diagnostic Considerations

Keratoconus should be differentiated from other causes of corneal steepening and irregular oblique astigmatism, imprecise variable subjective refractions, and non-inflammatory central corneal scarring. These may include corneal surgery, healed infections, and trauma.

Stromal striations similar to Vogt striae occur when corneas swell (rather than thin) from either hypoxia (associated with wear of contact lenses) or with early Fuchs corneal dystrophy.

Iron depositions in the basal epithelium (similar to a Fleischer ring) can occur in any area of relative depression in the corneal surface (eg, in association with pterygium, surgical scars, and central depressions from refractive surgery).

Pellucid marginal degeneration is often considered a variant of keratoconus. In pellucid marginal degeneration, corneal thinning occurs about 1 mm above the inferior limbus, resulting in advanced against-the-rule corneal astigmatism that may be observed on corneal topography or tomography.

Terrien marginal corneal degeneration is a mildly inflammatory disease, usually of the superior limbus. This disease can also induce irregular against-the-rule astigmatism and corneal thinning (often with vascularization and lipid deposits).

Keratoglobus is an extremely rare corneal disease in which the entire cornea, from limbus to limbus, thins, sometimes to the point where spontaneous perforation becomes possible. Keratoglobus is probably unrelated to keratoconus.

Posterior keratoconus is another extremely rare disease (or nonexistent), in which the posterior corneal surface suffers a loss of substance. This condition is probably unrelated to keratoconus.

Posterior polymorphous corneal dystrophy can lead to keratoconic-like steep cornea.[21]

Differential Diagnoses

 

Workup

Laboratory Studies

No laboratory workup is necessary in keratoconus.

Careful refraction, slit-lamp biomicroscopy, corneal topography, and corneal tomography allow the clinician to observe evidence and progression of keratoconus.

Imaging Studies

Corneal topography and corneal tomography are the standard diagnostic imaging tools used for the detection of keratoconus. These are especially useful when the typical biomicroscopy signs of Vogt striae and Fleischer ring are absent.

Corneal topography and tomography[25]

This commonly shows inferior corneal steepening in keratoconus, although a small percentage of patients with keratoconus show central astigmatic changes.

An even smaller number show superior peripheral steepening. Pellucid marginal degeneration typically shows an inferior lobster claw like map due to against-the-rule astigmatism.

Procedures

Pachymetry shows a thinner cornea paraxially.

Histologic Findings

All layers of the cornea are affected by keratoconus.

Superficial epithelial cells located at the nodule are elongated and arranged in a whorl-like fashion.

Iron deposition in the basal corneal epithelial cells form the characteristic Fleischer ring.

Localized breaks are present in the basement membrane.

A decrease in the number of stromal collagen lamellae is noted, as well as a loss of the fibular arrangement within the lamellae.[26]

Folds and ruptures occur in the Descemet membrane. Some studies have reported endothelial cell loss in association with Descemet rupture.

Cornea thinning is caused by the splitting of the lamellae into multiple bundles of collagen fibrils.[26]

Grading

Many grading are systems available to quantify the severity of keratoconus. Most systems consider the amount of corneal irregularity through higher-order aberrations and corneal thickness. Various nomograms have been proposed to quantify keratoconus, although no standard protocol is used for treatment.

Findings are as follows:

  • Normal: No clinical signs of keratoconus, no scissoring on retinoscopy, and symmetrical astigmatism
  • Keratoconus suspect: The fellow eye of an individual with keratoconus, with mild inferior steepening on topography and no clinical signs of keratoconus; the average K reading is less than 47 D
  • Forme fruste keratoconus: The fellow eye of an individual with keratoconus, with steeping seen on corneal topography and some corneal thinning seen on corneal tomography
  • Early keratoconus: No findings of keratoconus on slit-lamp examination; scissoring on retinoscopy; average K reading of less than 47 D
  • Keratoconus: Stromal corneal thinning on slit-lamp evaluation accompanied by one or more of the following clinical signs: Vogt striae, iron ring, Munson sign, scissoring on retinoscopy
 

Treatment

Medical Care

The current paradigm of care for keratoconus has shifted from not only correcting the vision but also slowing the disease process.

Rigid contact lenses and scleral gas-permeable lenses are the mainstay vision treatments for keratoconus.

Patients with early keratoconus may successfully use spectacles or spherical/toric soft contact lenses. They may even rarely find that spectacle vision is superior to rigid contact lenses. More sophisticated soft contact lenses with aberration-controlled designs are now available and yield variable success.

As the irregular astigmatism advances, rigid gas contact lenses provide better visual acuity for moderate to advanced keratoconus. When rigid contact lenses are no longer tolerated, some patients can maintain contact lens wear and usable visions with piggyback contact lenses or scleral contact lenses.

Scleral lenses are popular because of their excellent vision with improved comfort over cornea rigid gas-permeable contact lenses. Gas-permeable scleral lenses should be made of the highest oxygen-transmissible (Dk) material, and the tear layer should not be excessive to minimize hypoxia.[27]

Contact lens wear is often complicated by episodes of intolerance, allergic reactions (eg, giant papillary conjunctivitis), corneal abrasions, neovascularization, and other problems, sometimes leading to total intolerance. Surgical care is recommended when the best corrected visual acuity achieved with contact lenses is worse than 20/40 vision or when contact lenses and scleral lenses are no longer tolerated.

Surgical Care

Surgical care is differentiated among (1) treating the progression of keratoconus with ultraviolet corneal collagen cross-linking (UV-CXL), (2) removing corneal scars to improve contact lens tolerance, and (3) improving keratoconus-induced poor vision keratoconus with intrastromal corneal rings and corneal transplants. Surgery to improve visual acuity is elected when the best-corrected vision achieved with contact lenses or scleral lenses is worse than 20/40 or when contact lenses are no longer tolerated. Patients may still require contact lenses after surgical correction.[28]

Ultraviolet corneal collagen cross-linking

UV-CXL is the only procedure that is believed to slow the progression of keratoconus. It is used to increase the rigidity of the cornea by inducing additional cross-links within or between collagen fibers using UVA light and a photomediator, riboflavin, with the goal of slowing, possibly stabilizing, and even perhaps reversing, the progression of corneal ectasia in patients with keratoconus. When exposed to ultraviolet A radiation, riboflavin produces oxygen free radicals that initiate the creation of new covalent bonds. These bridge the amino groups of collagen fibrils, increasing the rigidity of corneal tissue.

Riboflavin 5´-phosphate topical ophthalmic (Photrexa, Photrexa Viscous) was approved by the US Food and Drug Administration (FDA) in April 2016 for use in corneal collagen cross-linking (CXL) in combination with the KXL System for the treatment of progressive keratoconus. Both Photrexa and Photrexa Viscous (in 20% dextran) topical ophthalmic solutions are used during various stages of the procedure with the electronic device (KXL System), which irradiates the solutions with ultraviolet A light after they have been applied to the debrided cornea.

Variations of UV-CXL include including accelerated cross-linking[29] and UV-CXL corneal epithelium intact (epi-on) or removed (epi-off) techniques.[30, 31] UV-CXL has also been combined with same-day photorefractive keratectomy (PRK),[32, 33] ICRS,[34] and phakic intraocular lens[35] to improve the corneal integrity prior to surgery on keratoconic eyes. UV-CXL generally does not improve visual acuity (or at most improves 1-2 lines), although UV-CXL improves corneal clarity over untreated keratoconic corneas.[36]

Long-term studies are still needed to determine the success and adverse effects of UV-CXL, as well as the long-term biomechanical effect. Current studies are showing good short-term results and some good long-term results 7-10 years postprocedure. One study of 34 eyes in 24 patients showed that the minimum keratometry reading, maximum keratometry reading, keratometry reading over the apex of the keratoconus, and mean astigmatism were significantly lower 10 years after treatment. Two eyes in the study required repeat CXL, and one eye worsened.[37]

UV-CXL is not recommended in thinner corneas because of the risk of endothelial damage. Currently, there is no effective way to measure collagen turnover, so the stability of the collagen cross-links remains a concern. Complications of UV-CXL have included corneal haze,[38] continual progression of keratoconus,[39] and, more rarely, corneal scarring, diffuse lamellar keratitis,[40] corneal melting,[41] persistent corneal edema,[42] endothelial cell density loss,[43] and herpetic keratitis.[44, 45, 37]

Currently, CXL treatment is most effective in patients with progressive keratoconus who are aged 16-40 years and have a minimum corneal thickness of 400 microns, a maximum keratometry of < 60D, and no other known corneal diseases.[46]

More studies are also needed to identify high-risk patients perhaps related to their age, diagnosis, corneal shape, and/or stages of ectasia.

Surgical removal of nodular scars

Surgically removing central nodular scars by shaving the corneal surface (superficial keratectomy with a blade or excimer laser phototherapeutic keratectomy) may improve contact lens tolerance, decrease the rate of associated corneal abrasions, and preclude the need for corneal transplant.

Intrastromal corneal rings

Intrastromal corneal rings (ICRS) are polymethyl methacrylate segments implanted into the corneal stroma to reduce corneal distortion by flattening the steep areas of the keratoconic eye. Although not often fully successful, they are an option for patients who (1) are intolerant to contact lenses, (2) have clear central corneas, (3) have corneas with a thickness of at least 400 µm, and (4) retain penetrating keratoplasty as a remaining option. ICRS has been found to be more successful in mild than in advanced disease. ICRS does not halt the progression of keratoconus but may somewhat improve the unaided visual function of the patient after the disease is stable. Visual recovery may range from 3 months to a year after the procedure. ICRS is now being combined with CXL, although long-term results are still pending.

Bowman layer transplantation

Midstromal transplantation of Bowman layer (also known as anterior limiting lamina [ALL]) is a newer procedure used to flatten and strengthen advanced keratoconic corneas that may be too thin for UV-CXL. A midstromal pocket is created with air. The Bowman layer is removed and replaced by a donor Bowman layer graft. The overall flattening of the cornea could make contact lens wear more comfortable and hence postpone PKP or DALK indefinitely.[47] Bowman layer transplantation usually improves 1-2 lines of visual acuity.

Deep anterior lamellar keratoplasty

Deep anterior lamellar keratoplasty (DALK) is becoming the preferred surgical option for keratoconic eyes without hydrops because of the avoidance of endothelial rejection, quicker heal time, and increased wound strength.[48, 49] Improved graft survival compared to PKP is still controversial.[50] Currently, DALK represents 10%-20% of all keratoconic transplants and 30% when hydrops are excluded.[51] Visual acuity results of DALK are similar if not slightly inferior to those of PKP in patients who do not have deep central corneal scarring.

Penetrating keratoplasty

Penetrating keratoplasty (PKP) is still the more commonly performed surgery used to treat keratoconus in patients whose vision is not correctable to better than 20/40. PKP yields good success rates, especially in eyes with endothelial dysfunction and central opacities, resulting in clear visual axes in greater than 90% of all cases. PKP for keratoconus exhibits excellent visual and survival results, but young patients may require one or more grafts during their lifetime.[52] Approximately 2.4%-20% of patients with keratoconus will require PKP, although this trend is decreasing owing to improved contact lenses and other surgical procedures.[18]

The introduction of the femtosecond laser to trephine the recipient and donor tissues has improved tissue apposition and hastened healing. Best corrected visual acuities range from 20/50 to 20/100 after PKP, although visual acuities fall to less than 20/200 in 18.9% of advanced keratoconic eyes 15 years after surgery.[53] PKP requires continuing professional care to monitor for rejection, suture-related problems, wound dehiscence, and other difficulties. Although extremely rare, keratoconus can recur in a graft. Rejection rates range from 5.8%-41% during the first two years postsurgery.[54, 55, 56] Most patients will require spectacles and/or contact lenses following surgery.

Consultations

Consult with a cornea specialist (a graduate of a cornea fellowship program) and/or contact lens specialist who provides appropriate (primarily rigid gas-permeable and scleral contact lens) contact lens care.

An ophthalmologist who is a cornea specialist assists in identifying appropriate clinical conditions and timing for surgical intervention, such as superficial keratectomy, PKP, DALK, Bowman layer transplantation, ICRS, or UV-CXL. Alternatively, topography-guided conductive keratoplasty has been shown to be modestly effective in reshaping the cornea in keratoconic eyes, at least temporarily.

A specialty contact lens practitioner (usually an optometrist but can be an optician or ophthalmologist) monitors contact lens care to optimize vision while minimizing complications of contact lens wear. This practitioner also helps to establish the appropriate clinical conditions and timing of surgical intervention, should this become necessary.

Psychiatric care may also be beneficial given that depressive disorders have been associated with the vision impairment caused by keratoconus.[57, 58, 59]

Genetic counseling may also be beneficial to pregnant patients with keratoconus given the genetic nature of the condition. Although keratoconus is multifactorial, influenced by environmental and biochemical factors, multiple genes are known to be involved, and there is a high prevalence of family history.

Activity

Patients should avoid (vigorous) eye rubbing.

Prevention

Patients should avoid eye rubbing.

Long-Term Monitoring

Frequently observe patients with keratoconus, especially because most wear contact lenses, which can produce complications including hypoxia and giant papillary conjunctivitis. Examine the upper eyelids via lid eversion in all contact lens wearers.

Even in the absence of signs or symptoms of complications, contact lens care should be provided at 4-month to 6-month intervals to promptly address changes in fit or optics, as well as detecting asymptomatic complications and early intolerance.

Patients with keratoconus who use contact lenses often have corneal abrasions,[60] particularly if corneal steepening has made the current rigid contact lens fit flat. Addressing such problems may preclude increased scarring, which could necessitate PKP.

 

Medication

Medication Summary

The only FDA-approved medication to treat the progression of keratoconus is riboflavin 5´-phosphate ophthalmic solution. It is a photoenhancer indicated for use with ultraviolet (UV) A exposure in the procedure for corneal collagen cross-linking (CXL).

Antihistamine/mast cell–stabilizing topical medications, antihistamines, mast cell stabilizers, nonsteroidal anti-inflammatory (NSAID), and, occasionally, steroids are helpful in controlling the often concomitant signs of ocular allergies, especially pruritus, that can lead to eye rubbing. These medications can also help with giant papillary conjunctivitis, which is a common complication of contact lens wear. Steroids should be used only after consideration of increased risks of cataracts, glaucoma, and decreased ability to resist infection. Cyclosporine ophthalmic emulsion is helpful in managing the inflammatory and dry-eye components of the disease.

Episodes of hydrops may require treatment with hyperosmotics to reduce corneal swelling or topical steroid drops to reduce inflammation. Topical antibiotics are used for suspected infection.

Photoenhancers

Class Summary

Under the conditions used for corneal collagen cross-linking, riboflavin 5´-phosphate functions as a photoenhancer and generates singlet oxygen, which is responsible for the cross-linking. Riboflavin and UVA corneal CXL elicits a stiffening effect on the corneal stroma, which increases its biomechanical strength, thus enabling the arrest of the progression of the disease.

Riboflavin 5'-phosphate ophthalmic (Photrexa, Photrexa Viscous)

Riboflavin 5´-phosphate sodium (vitamin B2) is the precursor of 2 coenzymes, flavin adenine dinucleotide and flavin mononucleotide, which catalyze oxidation/reduction reactions involved in a number of metabolic pathways. It is indicated for use in corneal collagen cross-linking in combination with the KXL System for the treatment of progressive keratoconus. Both the viscous solution (in 20% dextran) and the regular solution are used topically during the corneal CXL procedure.

Antihistamines/Mast cell stabilizer, ophthalmic

Class Summary

Mast cell stabilizers treat the long-term phases of ocular allergies and specifically giant papillary conjunctivitis (GPC), which can result from contact lens wear. GPC primarily appears to be a Gel-Coombs type 1 hypersensitivity disease. The primary pathological event is inappropriate degranulation of the conjunctival mast cells, which release many inflammatory mediators, such as histamine (resulting in itch). Pure mast cell stabilizers are indicated for long-term use after the acute phase of symptoms abates. They are well tolerated. Symptoms may include burning. Their four-times-a-day dosing decreases the rate of compliance and may result in treatment failure.

Azelastine 0.05% (Optivar)

Antihistamine and mast cell stabilizer.

Alcaftadine ophthalmic (Lastacaft)

Alcaftadine is an H1-receptor antagonist. It inhibits histamine release from mast cells, decreases chemotaxis, and inhibits eosinophil activation. Lastacaft is dosed at once a day to improve patient compliance.

Bepotastine (Bepreve)

Bepreve is a histamine H1 receptor antagonist indicated for the treatment of itching associated with allergic conjunctivitis. It is dosed twice a day in each eye.

Epinastine (Elestat)

Epinastine is a direct histamine-1 receptor antagonist. It is indicated for symptoms due to allergic conjunctivitis. Its recommended dosage is twice a day.

Ketotifen fumarate 0.0.25% (Zaditor, Alaway, Claritin Eye, GoodSense Itchy Eye, Eye Itch Relief)

Ketotifen is a relatively selective, noncompetitive H1-receptor antagonist and inhibitor of histamine release from mast cells. This is an over-the-counter product. Recommended frequency is twice a day.

Olopatadine ophthalmic (Pataday, Patanol, Pazeo)

Olopatadine is a histamine H1 receptor antagonist that inhibits the release of histamine from mast cells and histamine-induced effects on conjunctival epithelial cells. Pazeo's recommended dosing is once a day, which can improve patient compliance.

Mast cell stabilizers

Class Summary

These agents are used to manage signs and symptoms of long-term ocular allergies, which can lead to patient discomfort and increased vigorous eye rubbing.

Cromolyn sodium

Cromolyn sodium is a mast cell stabilizer that inhibits histamine and SRS-A from mast cells. It was the first drug of its class. Its recommended dosage is four times a day.

Nedocromil sodium (Alocril)

Nedocromil inhibits the release of various inflammatory cell mediators (mast cell stabilizer). It has greater efficacy than cromolyn sodium. Its recommended dosage is twice a day.

Pemirolast ophthalmic (Alamast)

Pemirolast is a mast cell stabilizer indicated for the prevention of itching due to allergic conjunctivitis. Its recommended dosage is four times a day.

Second generation antihistamines

Class Summary

These agents inhibit many aspects of the inflammatory response from inciting agents: edema, capillary dilation and proliferation, leukocyte migration, and fibroblast proliferation.

Azelastine ophthalmic (Optivar)

Azelastine ophthalmic is a selective H1-receptor competitor with H1-receptor sites on effector cells. It also exhibits H2-blocking properties. It inhibits the release of histamine and other mediators involved in the allergic response. Its recommended dosage is twice a day.

Emedastine (Emadine)

Emedastine difumarate is a relatively selective H1 receptor antagonist that appears to be devoid of effects on adrenergic, dopaminergic, and serotonin receptors. It affects both the early and late phases of the ocular allergic reaction. Its recommended dosage is four times a day.

Corticosteroids

Class Summary

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body's immune response to diverse stimuli. They are used to manage ophthalmic inflammation of giant papillary conjunctivitis resulting from keratoconus and contact lens wear.

Loteprednol etabonate (Lotemax, Alrex)

Loteprednol modulates the activity of prostaglandins and leukotrienes. Placebo-controlled studies have demonstrated that loteprednol reduces the signs and symptoms of GPC after 1 week of treatment, continuing for up to 6 weeks while on treatment. It has a reduced risk of increasing the intra-ocular pressure by rapidly converting into inactive metabolites after corneal penetration. Its recommended dosage is four times a day.

Hyperosmolar diuretics

Class Summary

These agents may reduce inflammation in cornea by creating an osmotic gradient across an intact blood barrier.

Sodium chloride hypertonic, ophthalmic (Muro 128, Altachlore, Sochlor)

Used for temporary relief of corneal edema during episodes of corneal hydrops. The solution is recommended to be used every 3-4 hours, and an ointment is recommended for nighttime use.

Immunomodulators

Class Summary

These agents may have anti-inflammatory effects.

Cyclosporine ophthalmic (Restasis)

Immunomodulator with anti- inflammatory effects. Used to manage dry eyes that accompany keratoconus and (off label) possible ocular inflammation associated with keratoconus. The drops are recommended to be used twice a day. If contact lenses are to be worn, wait 10-15 minutes before wearing contact lenses.