Keratoconus is an uncommon corneal disorder where the central or paracentral cornea undergoes progressive thinning and steepening causing irregular astigmatism.
Keratoconus adult eye (ICD-9 #371.60).
Keratoconus is an uncommon corneal disorder where the central or paracentral cornea undergoes progressive thinning and steepening causing irregular astigmatism.
Etiology is unknown. However, it is associated with atopy, Down’s Syndrome, Leber’s congenital amaurosis, and Ehler’s Danlos/connective disorders. The hereditary pattern is neither prominent nor predictable, but positive family histories have been reported. The prevalence of keratoconus if often reported to be 1 in 700.
- Eye rubbing, associated with atopy or vernal keratoconjunctivitis
- Sleep apnea
- Connective tissue disorders
- Floppy eyelid syndrome
- Retinitis pigmentosa
- Positive family history
- Down syndrome
Keratoconus can show the following pathologic findings; fragmentation of Bowman’s layer, thinning of stroma and overlying epithelium, folds or breaks in Descemet’s membrane, and variable amounts of diffuse corneal scarring.
Histopathology studies demonstrated breaks in or complete absence of Bowman’s layer, collagen disorganization, scarring, and thinning. The etiology of these changes is unknown, though some suspect changes in enzymes that lead to the breakdown of collagen in the cornea. While a genetic predisposition to keratoconus is suggested, a specific gene has not been identified. Although keratoconus does not fulfill the criteria for inflammatory disease, recent studies show a significant role of proteolytic enzymes, cytokines, and free radicals (MMP-9, IL-6, TNF-α) even in subclinical disease, showing a quasi-inflammatory characteristic in keratoconus. 
No preventive strategy has been proven effective to date. Some feel that eye rubbing or pressure (eg. sleeping with the hand against the eye) can cause and/or lead to the progression of keratoconus. Patients should be informed not to rub their eyes. In some patients, avoidance of allergens and treatment of ocular surface disease may help decrease eye irritation and therefore decrease eye rubbing.
Diagnosis can be made by slit-lamp examination and observation of central or inferior corneal thinning. Computerized videokeratography is useful in detecting early keratoconus and allows following its progression. Ultrasound pachymetry can also be used to measure the thinnest zone on the cornea. New algorithms using computerized videokeratography have been devised which now allow the detection of forme fruste, subclinical, or suspected keratoconus. These devices may allow better screening of patients for prospective refractive surgery.
The majority of cases of keratoconus are bilateral, but often asymmetric. The less affected eye may show a high amount of astigmatism or mild steepening. Onset is typically in early adolescence and progresses into the mid-20’s and 30’s. However, cases may begin much earlier or later in life, and progression may also persist beyond the 30's. There is a variable progression for each individual. There is often a history of frequent changes in eyeglasses prescription that do not adequately correct vision. Another common progression is from soft contact lenses to toric or astigmatism correcting contact lenses, to rigid gas permeable contact lenses. A complete ocular and medical history should be taken, including change in eyeglass prescription, decreased vision, history of eye rubbing, medical problems, allergies, and sleep patterns.
A thorough and complete eye exam should be performed on any patient suspected of having keratoconus.
The general health of the eye should be assessed, and appropriate ancillary tests should be done to assess corneal curvature, astigmatism, and thickness. The best potential vision should also be evaluated. Many of the potential exam components are listed below:
- Measurement of uncorrected visual acuity
- Measurement of visual acuity with current correction (the power of the present correction recorded) at distance and when appropriate at near.
- Measurement of best-corrected visual acuity with spectacles and hard or gas permeable contact lenses (with refraction when indicated)
- Measurement of pinhole visual acuity
- Retinoscopy to check for scissoring reflex
- Slit-lamp biomicroscopy of the anterior segment including lid tightness and papillae in upper tarsal conjunctiva
- Keratometry/Computerized Topography/Computerized Tomography/Ultrasound Pachymetry
Early signs of Keratoconus include:
- Asymmetric refractive error with high or progressive astigmatism
- Keratometry showing high astigmatism and irregularity (the axis that does not add to 180 degrees)
- Scissoring of the red reflex on retinoscopy
- Inferior steepening, skewed axis, or elevated keratometry values on K reading and computerized corneal topography
- Corneal thinning, especially in the inferior cornea. Maximum corneal thinning corresponds to the site of maximum steepening or prominence.
- Rizutti’s sign or a conical reflection on the nasal cornea when a penlight is shone from the temporal side
- Fleischer ring, an iron deposit often present within the epithelium around the base of the cone. It is brown in color and best visualized with a cobalt blue filter
- Vogt’s striae, fine, roughly vertically parallel striations in the stroma. These generally disappear with firm pressure applied over the eyeball and re-appear when pressure is discontinued.
Later signs of Keratoconus include:
- Munson’s sign, a protrusion of the lower eyelid in downgaze.
- Breaks in Bowman’s membrane
- Acute hydrops, a condition where a break in Descemet’s membrane allows aqueous enter into the stoma causing severe corneal thickening, decreased vision, light sensitivity, tearing, and pain.
- Stromal scarring after the resolution of acute hydrops, which paradoxically may improve vision in some cases by changing corneal curvature and reducing irregular astigmatism.
Progressive changes in vision not easily corrected with eyeglasses.
Diagnosis is made based on the history of changing refraction, poor best spectacle-corrected vision, scissoring reflex on retinoscopy, abnormalities in keratometry, corneal topography, and corneal tomography, in association with corneal thinning and inferior steepening; characteristic slit-lamp findings can often be seen.
Diagnostic procedures include:
- Slit-lamp examination
- Retinoscopy (assessment of scissor reflex)
- Hard or gas permeable contact lens trial as improved vision with lenses eliminates other sources of poor vision, including amblyopia
- Measurement of K values
- Ultrasound pachymetry
- Computerized corneal topography
Example of Early Keratoconus as evidenced on a Placido-disc based topographic evaluation
- Computerized corneal tomography (Rotating Scheimpflug, Rotating Slit Beam Photography)
Example of Keratoconus as evidenced on a Pentacam Scheimpflug evaluation
- Pellucid marginal degeneration
- Contact lens-induced corneal warpage
- Corneal ectasia post-refractive laser treatment
The goals of treatment are to provide functional visual acuity and to halt changes in the corneal shape if progressing.
For visual improvement and astigmatism management, spectacles or soft toric contact lenses can be used in mild cases. Rigid gas permeable contact lenses are needed in the majority of cases to neutralize the irregular corneal astigmatism. The majority of patients that can wear hard or gas-permeable contact lenses have a dramatic improvement in their vision. Specialty contact lenses have been developed to better fit the irregular and steep corneas found in keratoconus; these include (but not limited to) RoseK, custom-designed contact lenses (based on topography and/or wavefront measurements), semi-scleral contact lenses, piggyback lens use ( hard lens over soft lens), scleral lenses, hybrid lenses, and PROSE (prosthetic replacement of the ocular surface ecosystem). Those patients that become contact lens intolerant or do not have an acceptable vision, typically from central scaring, can proceed to surgical alternatives.
The primary treatment for progressive keratoconus, or keratoconus in young patients likely to progress at some point, is corneal collagen cross-linking. A drug and device combination product (Photrexa Viscous, Photrexa and the KXL System) for epi-off corneal collagen cross-linking was approved by the FDA in the Spring of 2016. Conventional corneal cross-linking has been available under CE mark throughout Europe for more than 10 years earlier throughout Europe. Corneal collagen cross-linking is a minimally invasive treatment using riboflavin and UV light to induce stiffening of the corneal stroma through the formation of additional cross-link bonds within the extracellular matrix of the stromal collagen. In the conventional procedure, the corneal epithelium is debrided using standard clinical techniques, followed by soaking of the cornea with drops of ophthalmic riboflavin 5-phosphate solution. The riboflavin sensitizer is then activated with exposure of the cornea to UV light for a period of 30 minutes. Variations of this conventional "epithelium-off" technique involve higher intensities of UV for shorter time periods (accelerated cross-linking) or non-removal of the epithelium ("epithelium-on") techniques. The pivotal FDA trials and most European data sets demonstrate a high success rate for the conventional epithelium-off cross-linking approach. Other approaches have shown some promise and success but overall have been less consistent and reliable in their abilities to halt keratoconus.
Medical therapy for patients who have an episode of corneal hydrops involves acute management of the pain and swelling. Patients are usually given a cycloplegic agent, sodium chloride (Muro) 5% ointment, and may be offered a pressure patch. After the pressure patch is removed patients may still need to continue sodium chloride drops or ointment for several weeks to months until the episode of hydrops has resolved. Patients are advised to avoid vigorous eye rubbing or trauma.
Patients are usually followed on a 3 to 6-month basis to monitor the progression of the corneal thinning, steepening, the resultant visual changes, and to re-evaluate the need for cross-linking and patient contact lens fit and care. Patients with hydrops are seen more frequently until it resolves.
Patients with associated medical conditions should have these attended to properly. Atopic or vernal conjunctivitis should be treated using topical anti-histamines, mast cell stabilizers, or anti-inflammatory/immunomodulatory treatments such as topical steroids, cyclosporine, tacrolimus, or lifitegrast.
Since the incidence of sleep apnea is very high in keratoconus, and because this condition may contribute to the pathogenesis of keratoconus and other medical conditions, all keratoconus patients should be questioned regarding sleep habits. Sleep studies and CPAP mask wear if found necessary are recommended for at-risk patients.
Medical follow up
Since the availability of corneal collagen crosslinking, patients are usually followed on a 3 to 6-month basis to monitor the progression of the corneal thinning and steepening and the resultant visual changes. This allows the physician to determine if the cross-linking treatment is indicated. Cross-linking is indicated at the onset of documented progression of keratoconus to improve the prognosis of the condition and preserve visual function. These follow-up visits also allow for re-evaluations of contact lens fit and care.
The majority of patients with keratoconus can be fitted with contact lenses, and their vision significantly improves with that. When patients become intolerant or no longer benefit from contact lenses, surgery is the next option. If keratoconus is effectively stabilized with corneal cross-linking while patients are still able to achieve adequate visual function with spectacles or contact lenses, further interventions may not be required. Surgical options include intrastromal corneal ring segments (ICRS), deep anterior lamellar keratoplasty (DALK), and penetrating keratoplasty (PK).
Non-FDA approved treatments, which typically have less evidence-based information available on safety and efficacy, including the use of corneal cross-linking experimentally combined with excimer laser treatment, conductive keratoplasty, and/or ICRS. Some surgeons will use phakic IOLs to address high myopia and some of astigmatism.
ICRS have also been approved for the treatment of mild to moderate keratoconus in patients who are contact lens intolerant. In these cases, patients must have a clear central cornea and a corneal thickness of > 450 microns where the segments are inserted, approximately at 7 mm optical zone. The advantage of ICRS is that they require no removal of corneal tissue, no intraocular incision, and leave the central cornea untouched. Most patients will need spectacles and/or contact lenses post-operatively for best vision but will have flatter corneas and easier use of lenses. If a patient does not gain the expected results, ICRS can be removed, and then other surgical options can be considered.
DALK involves the replacement of the central anterior cornea, leaving the patient’s endothelium intact. The advantages are that the risk of endothelial graft rejection is eliminated, and there is less risk of traumatic rupture of the globe in the incision, since the endothelium and Descemet’s and some stroma are left intact, and faster visual rehabilitation. There are several techniques utilized including, manual dissection and big bubble technique to remove the anterior stroma while leaving Descemet’s layer and endothelium untouched. However, the procedures can be technically challenging requiring conversion to penetrating keratoplasty, and post-operatively there is the possibility of interface haze leading to a decrease in BCVA; it is not clear if astigmatism is better treated with DALK vs PK. PK has a high success rate and is the standard surgical treatment with a long track record of safety and efficacy. Risks of this procedure include infection and cornea rejection and risk of traumatic rupture at the wound margin. Many patients after PK may still need hard or gas-permeable contact lenses due to residual irregular astigmatism. Any type of refractive procedure is considered a contraindication in keratoconic patients due to the unpredictability of the outcome and risk of leading to increased and unstable irregular astigmatism.
Surgical follow up
Following any corneal surgical procedure, patients need to be followed to complete visual rehabilitation. Most patients still require vision correction with spectacles or contact lenses, and often hard or gas permeable lenses are required if high levels of astigmatism are present.
All surgical patients need to be followed to ensure wound healing, evaluation for infection, suture removal, and other routine eye care, such as testing for glaucoma, cataracts, and retinal disease. Graft rejection can occur after penetrating keratoplasty, requiring prompt diagnosis and treatment to ensure graft survival.
Infection, poor wound healing, cornea transplant rejection, corneal neovascularization, graft-host junction thinning, glare, irregular astigmatism, and high refractive error.
With early diagnosis and prompt intervention with corneal cross-linking, patients may retain adequate visual function with spectacle lenses or contact lenses throughout their lifetime. ICRS can provide long-term success for patients with keratoconus, but this is typically in conjunction with contact lens use, and some may ultimately require a corneal transplant to reach their goals of visual rehabilitation. While the prognosis for penetrating keratoplasty in a keratoconic patient is excellent, with most patients able to return to an active lifestyle and the pursuit of personal goals after visual rehabilitation with specialty contact lenses, long term maintenance therapy with steroid medications may be required. "Progression" of keratoconus, even after corneal surgery, has been reported, but it is not clear how common or to what extent this can occur.
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