Keratoconus

Keratoconus is a non-inflammatory, bilateral (but usually asymmetrical) disease of the cornea which results in progressive corneal steepening. It is characterised by para-central corneal thinning and ectasia so that the cornea takes the shape of a cone. Visual loss occurs primarily from myopia and irregular astigmatism and secondarily from corneal scarring.

Duddell in 1729, described a patient with protruding conical corneas and associated poor vision. Keratoconus was initially broadly defined based on the shape and location of the cone. These included round or nipple cones with a central conical protrusion, and oval cones, often with inferior sagging.

Marc Amsler was the first one to describe early corneal topographic changes in keratoconus patients using keratoscope/ placido disc (ophthalmic instrument for detecting abnormal curvature of the cornea). He categorised keratoconus into clinically recognisable stages as:

  • Latent stage: Latent stage was recognisable by placido disc only.
  • Early stage: Early stages were subdivided into two categories as:

 

-       Keratoconus fruste, which entailed 1- to 4-degree deviation of horizontal axis of the placido disc.

-       Early or mild keratoconus, which entailed 5- to 8-degree deviation of horizontal axis.

The prevalence of keratoconus in general population appears to be relatively high and is likely to be higher when examined with corneal topography (also called photokeratoscopy or videokeratography). Corneal topography is a computer assisted diagnostic tool that creates a three- dimensional map of the surface of the cornea. Keratoconus occurs in all ethnic groups with no male or female preponderance. It is commonly an isolated ocular condition, but sometimes coexists with other ocular and systemic diseases.

Commonly recognised ocular associations include vernal keratoconjunctivitis, retinitis pigmentosa and Leber congenital amaurosis; many of the connective tissue disorders (e.g. Ehlers-Danlos and Marfan syndromes), mitral valve prolapse, atopic dermatitis and Down syndrome.

Particular risk factors include atopic history, especially ocular allergies, rigid contact lens wear and vigorous eye rubbing. Most keratoconus cases appear spontaneously, but few may show evidence of genetic transmission.

Keratoconus generally manifests at puberty, and is progressive until third to fourth decade of life when it usually arrests. Sometimes, however, it may commence later in life and progress or arrest at any age.

 

 

References:

Agarwal Amar, Agarwal Athiya, Jacob Soosan. Refractive Surgery. Second Edition. Jaypee Brothers Medical Publishers (P) Ltd 2009. P 19- 24.

U Rajendra Acharya, Ng Eddie YK, Suri Jasjit S. Image Modeling of the Human Eye. AR TECH HOUSE, INC. 2008. P 9- 11.

Khurana A K. Comprehensive Ophthalmology. Sixth Edition. Jaypee Brothers Medical Publishers (P) Ltd 2015. P 30.

Foster C Stephen, Azar Dimitri T, Dohlman Claes H. Smolin and Thoft’s The CORNEA-Scientific Foundations & Clinical Practice. Lippincot Williams & Wilkins. Fourth Edition. 2005. P 889- 910.

Yanoff Myron, Duker Jay S. Ophthalmology. Third Edition. Mosby Elsevier 2009. P 299- 302.

Wang Ming, Swartz Tracy S. Keratoconus & Keratoectasia - Prevention, Diagnosis, and Treatment. SLACK Incorporated 2010. 

Denniston Alastair K O, Murray Philip I. Oxford Handbook of Ophthalmology. Third Edition. Oxford University Press 2014. P 258- 259.

Eagle Ralph C, Jr. Eye Pathology – An Atlas and Text. Second Edition. Lippincott Williams & Wilkins, a Wolters Kluwer business 2011. P 88.

Wang Ming, Swartz Tracy Schroeder. Irregular Astigmatism – Diagnosis and Treatment. SLACK Incorporated 2008. P 53- 59.

Barbara Adel. Textbook on Keratoconus- New Insights. Jaypee Brothers Medical Publishers (P) Ltd. 2012. 

Copeland Jr Robert A, Afshari Natalie A.Copeland and Afshari’s Principles and Practice of CORNEA Vol.1. Jaypee Brothers Medical Publishers (P) Ltd. 2013. P 819- 834.

Sihota Ramanjit, Tandon Radhika. Parsons’ Diseases of the Eye. Twenty second Edition. Reed Elsevier India Private Limited 2015. P 216- 218.

http://emedicine.medscape.com/article/1194693-overview

http://emedicine.medscape.com/article/1196836-overview#a1

http://eyewiki.org/Keratoconus

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762162

http://www.hindawi.com/journals/bmri/2015/795738

Saxena Sandeep. Clinical Ophthalmology: Medical and Surgical Approach. Second Edition. Jaypee- Highlights Medical Publishers, Inc. 2011.P 66- 69.

Nema HV, Nema Nitin. Textbook of Ophthalmology. Fifth Edition. Jaypee Brothers Medical Publishers (P) Ltd. 2008. P 169- 170.

Kalevar V. Clinical Ophthalmology. Ane Books India. 2008. P. 166.

McMahon TT, et al. A new method for grading the severity of keratoconus: the Keratoconus Severity Score (KSS). Cornea. 2006; 25(7): 794- 800.

Rabinowitz YS, Rasheed K. KISA% index: a quantitative videokeratography algorithm embodying minimal topographic criteria for diagnosing keratoconus. J Cataract Refract Surg. 1999; 25(10): 1327- 1335.

Maeda N, Klyce SD, Smolek MK. Automated keratoconus screening with corneal topography analysis. Invest Ophthalmol Vis Sci. 1994; 35(6): 2749- 2757.

Amsler M. Le keratocone fruste au javal. Ophthalmologica 1938; 96: 77- 83 (French).

Duddell B. A treatise of the Diseases of the horny-coat of the eye, and the various kinds of cataract. London: J Clark 1729.

Symptoms are highly variable and depend upon the stage of the disease. Early in the disease, there may be no symptoms. In advanced disease, there is significant diminution and distortion of vision.

  • Monocular polyopia (perception of multiple ‘ghost’ images in the eye).
  • Blurring of vision.
  • Decreased visual acuity.
  • Progressively poor vision, not corrected with eye glasses.
  • Impaired visual perception.
  • Decreased contrast sensitivity.
  • Streaking and flaring distortion around light sources.
  • Marked anisometropia (difference in vision of two eyes).
  • Glare.
  • Photophobia (increased sensitivity to light).
  • Eyestrain, in order to read clearly.
  • Poor vision at night.
  • Itching.

Monocular polyopia (perception of multiple ‘ghost’ images in the eye), decreased visual acuity, and decreased contrast sensitivity may be seen in other disorders, especially early nuclear sclerotic cataract.

The cause of keratoconus is not known. It may not be a single disorder, but rather a phenotypic expression of perhaps many causes, both genetic and environmental.

The inheritance pattern of keratoconus is incompletely defined. In the past it was believed that more than 90% of cases were sporadic. With the advent of videokeratography to assess family members, however, pedigrees have been analysed. These studies show corneal changes consistent with keratoconus in some family members, which suggest an autosomal dominant pattern of inheritance.

Keratoconus may be associated with wide variety of systemic and ocular conditions.

Systemic associations:

  • Atopy (a genetic predisposition to develop an allergic reaction): One of the most common associations of keratoconus is atopy and is seen in condition like vernal keratoconjunctivitis. Eye rubbing seen in systemic atopy may play a role in the development of keratoconus.
  • Down syndrome (Trisomy 21):  In Down syndrome (Trisomy 21), frequency of acute hydrops is higher, perhaps because of eye rubbing and/or these patients are treated infrequently with keratoplasty and their disease is allowed to progress further.
  • Ehlers-Danlos syndrome.
  • Marfan syndrome.
  • Crouzon syndrome.
  • Apert syndrome.

Ocular associations:

  • Leber’s congenital amaurosis.
  • Retinitis pigmentosa.
  • Retinopathy of prematurity.
  • Fuchs’ corneal endothelial dystrophy.
  • Posterior polymorphous dystrophy.

Given the relatively high prevalence of keratoconus in general population, some of the associations may be coincidental.

 

Studies suggest various contributory factors such as:

  • Enzyme abnormalities in corneal epithelium: Enzyme abnormalities such as increased expression of lysosomal enzymes (catalase and cathepsin) and decreased levels of inhibitors of proteolytic enzymes (tissue inhibitor matrix metalloproteinases), may play a role in corneal stromal degradation.
  • Differentially expressed corneal epithelium: Differentially expressed corneal epithelium between keratoconus and myopes (as controls) in both genetic expression and protein expression.
  • Molecular defect: Molecular defect producing unusual absence of water channel protein aquaporin 5 in keratoconus as compared to normal corneal epithelium.
  • Gelatinolytic activity: Gelatinolytic activity in stroma has been described, which may be due to decreased function of enzyme inhibitors.
  • Abnormalities in corneal collagen and its cross-linking: Abnormalities in corneal collagen and its cross-linking may be the cause of keratoconus.
  • Eye rubbing: Cytokine has been suggested as a mediator of eye rubbing and stromal degradation. Keratoconus in patients with atopic dermatitis, Down syndrome, and Leber congenital amaurosis, a congenital photoreceptor degeneration, could be related to forceful eye rubbing or the oculodigital reflex. The latter is a behavioural pattern seen in visually and mentally handicapped children who repeatedly strike their eyes with hands.
  • Hard contact lens wear.

 

 

Pathophysiology:

All layers of the cornea are believed to be affected by keratoconus, although the most notable features are the thinning of the corneal stroma, the fragmentation of the Bowman layer and the deposition of iron in the basal epithelial cells, forming the Fleischer ring. Folds and breaks in the Descemet’s membrane result in acute hydrops and striae, which produces variable amount of diffuse scarring.

Refraction, keratometry, corneal topography and slit- lamp (bio-microscopy) examination helps in reaching to the diagnosis of keratoconus.

Refraction: Patients with keratoconus often report blurring/impairment of vision due to progressive myopia and irregular astigmatism. There may be multiple unsatisfactory attempts in obtaining optimum correction with glasses. Spectacles and soft contact lenses may initially give satisfactory vision, but vision tends to decline over time and requires rigid gas-permeable contact lenses for correction.

Keratometry: Images of keratometry mires commonly will be steep, highly astigmatic, irregular, and often appear egg-shaped rather than circular or oval in keratoconus. A value of 47.2 Diopters (D) or greater is suggestive of keratoconus. These signs may be absent in some patients of keratoconus.

Corneal topography/Computerised videokeratography: is helpful in reaching a diagnosis, especially when the typical bio-microscopy signs of Vogt striae and Fleischer ring are absent. Several quantitative indices are available using corneal topography information to screen for keratoconus.

Ultrasonic pachymetry: Ultrasonic pachymetry may be useful to confirm corneal thinning in patients with suspected keratoconus on slit- lamp examination or videokeratography. Orbscan corneal topography system and Oculus Pentacam which provides both topography and pachymetry maps are particularly useful in making a diagnosis.

Keratoconus is differentiated according to severity of disease as well as shape of cornea.

Shape- based differentiation:

Conical shapes of cornea are differentiated as:

  • Nipple cones: Nipple cones have a diameter of 5mm or less and are located in the center or slightly below the center of the cornea.
  • Oval cones: Oval cones are larger in diameter and are inferonasally or inferotemporally to the center of the cornea.
  • Globus cones: Globus cones are large and involve about 75% of the surface of cornea and are least common.

Severity- based differentiation:

I. Mild keratoconus:

External and corneal signs are often absent or are minimal.

  • Spectacle correction: A history of multiple inadequate spectacle corrections of one or both eyes and it may show oblique astigmatism as well as moderate-to-high myopia on refraction.
  • Keratometry values: Irregularly astigmatic keratometry values, not necessarily on the steep side of normal (approximately 45 Diopters), are consistent with diagnosis.
  • Computer-assisted videokeratography: Computer-assisted videokeratography may reveal,

-       Inferior corneal steepening (approximately 80% of keratoconus patients),

-       Central corneal astigmatic steepening (approximately 15% of keratoconus patients),

-       Even bilateral temporal steepening (extremely rare).

  • Optical coherence tomography pachymetry (OCT pachymetry): Optical coherence tomography pachymetry shows paraxial corneal thinning.
  • Diagnostic rigid contact lens: On application of diagnostic rigid contact lens with its base curve equal to the flat keratometry reading after instilling fluorescein sodium dye, a typical nipple pattern is seen in the underlying tear film.
  • Corneal sensitivity: Corneal sensitivity is reduced.
  • Tear secretions: Tear secretions are decreased.

II. Moderate keratoconus:

  • Retinoscopy: On retinoscopy, there may be distortion of reflex which shows ‘scissoring reflex’.
  • Charleaux’s sign: Charleaux oil droplet reflex is a bright reflex from the conical apex surrounded by a dark circular shadow produced by corneal ectasia.  Charleaux’s sign or oil drop sign is visualised on observation of the cornea with the pupil dilated using a direct ophthalmoscope set on plano.
  • Munson sign: Munson sign is the ‘V’ shape protrusion produced in the lower lid by cornea on down gaze.
  • Rizutti’s sign: Rizutti’s sign is an arrowhead pattern at the nasal limbus being produced by focusing of a light beam shown from temporally across the cornea.
  • Prominent corneal nerves: There may be enhanced appearance of corneal nerves.
  • Vogt striae (fine stress lines): Patients may show Vogt striae (fine stress lines) in the deep stroma. These deep stromal stress lines clear when pressure is applied to the globe.
  • Fleischer ring: Deposition of iron in the basal epithelial cells in a ring shape (often partial) at the base of the conical protrusion, called the Fleischer ring.
  • Corneal scarring: Corneal scarring may be present at various levels.

-       Superficial corneal scarring, which may be fibular, nebular or nodular.

-       Deep stromal scarring perhaps represents resolved mini-hydrops.

-       Some patients show scarring at the level of the Descemet membrane, consistent in appearance with posterior polymorphous corneal dystrophy. This may be a variant of posterior polymorphous corneal dystrophy.

  • Keratometry values: Keratometry values are 45- 52 Diopters. There may be pulsation of the reflected images on standard keratometry because thinned cornea readily transmits the ocular pulse.

Similar pulsations of the mires on applanation tonometry may be noted.

  • Optical coherence tomography pachymetry: Optical coherence tomography pachymetry shows paraxial (usually inferior to the pupil) stromal thinning.

III. Advanced keratoconus:

  • Enhancement of all corneal sign, symptoms, and visual loss/ distortion, including Vogt striae, Fleischer ring, and/or scarring, is present.
  • Acute corneal hydrops: Acute corneal hydrops results in acute overhydration of the cornea and accumulation of fluid within the corneal stroma due to acute rupture of Descemet’s membrane. The overlying corneal epithelium may become oedematous, and fluid may leak through the corneal epithelium. The ruptured Descemet’s membrane curls in on itself, and over time endothelial cells spread over the posterior stromal defect.
  • Keratometry: Keratometry values are greater than 52 Diopters.

 

Grading keratoconus:

Several quantitative indices are available using corneal topography information to screen for keratoconic corneal shape factors. The two most commonly known indices are those of Rabinowitz and Maeda and Klyce.

I. Rabinowitz index: Rabinowitz created KISA% index, which provides an algorithm to quantify results from computerised videokeratoscopy. The KISA% index uses:

  • The corneal central keratometry (K value) value, which indicates central corneal steepening.
  • The inferior- superior dioptric asymmetry (I- S) value
  • The keratometric astigmatism (AST) index, which quantifies the degree of regular corneal astigmatism based on (SimK1- SimK2). Simulated keratometry (SimK) index provides information on the diopteric power of the flattest and most curved meridians. Numerically, it is expressed as K1 and K2, and the difference (SimK1- SimK2) between the two values provides a quantitative value of corneal astigmatism.
  • The skewed radial axis (SRAX) value: Skew of steepest radial axis measures the angle between the more curved superior semi- meridian and the more curved inferior semi- meridian.

 

Rabinowitz diagnostic criteria consist of three corneal topography derived indices, which, when abnormal in value, should alert the clinician to consider a diagnosis of keratoconus. These indices are:

 

  • K value (Central keratometry) quantifies the central steepening of the cornea that occurs in keratoconus. A value of 47.20 D or greater is suggestive of keratoconus.
  • I-S value (inferior- superior value) quantifies the inferior versus superior corneal diopteric asymmetry that occurs in keratoconus. A positive value indicates higher inferior curvature while a negative value indicates higher superior curvature. I-S values between 1.4D and 1.8D are defined as cut- off points for suspected keratoconus. I-S values higher than 1.8D are defined as cut- off points for clinical keratoconus.
  • KISA% incorporates the K, I-S values, SRAX and AST with a measure quantifying regular and irregular astigmatism into one index. This index is highly sensitive and specific in separating normal from keratoconic corneas. A value of greater than 100% is highly suggestive of keratoconus, and the range from 60 to 100% represents suspected keratoconus.

II. Maeda and Klyce computer expert program: Maeda and Klyce designed a computer expert program, based on linear discriminant analysis of 8 indices drawn from the corneal map and a binary decision tree. The program assigns the topographical map a quantitative percentage score of the severity of keratoconus called the keratoconus index% (KCI%). A value of greater than zero is believed to be suggestive of keratoconus.

III. McMahon and colleague keratoconus severity score (KSS): McMahon and colleagues and the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study, have proposed a method called the keratoconus severity score (KSS) for grading the severity of keratoconus. The KSS score utilises:

  • Clinical signs (Vogt’s striae, Fleischer ring, corneal scarring).
  • Two corneal topography indices (average corneal power and the root mean square (RMS) error for higher- order aberrations).
  • Manual interpretation of the topography map to form a 1-to-5 grading system.

Advantages of KSS score:

  • KSS system provides good reproducibility.
  • It is not limited to the use of one topographer.
  • Unlike KISA% index, it grades the severity of keratoconus rather than just identifying presence or absence of the condition.

 

Histopathology:

All layers of the cornea are affected by keratoconus. Keratoconus shows irregular epithelium, breaks in Bowman’s layer, and fibrosis filling in the breaks that extend beneath the epithelium. Iron deposition in the basal corneal epithelial cells forms the characteristic Fleischer ring. With hydrops, breaks at the layer of Descemet’s membrane are seen, with inward curling of Descemet’s membrane, which is otherwise normal. Some studies have reported endothelial cell loss in association with the rupture of the Descemet’s membrane.

 

Electron microscopy shows decreased thickness of the cornea with fewer lamellae. The collagen fibrils in the lamellae are thickened mildly and the space between fibrils is increased.

 

 

Differential diagnosis:

Keratoconus should be distinguished from other ectatic and thinning disorders such as:

  • Pellucid marginal degeneration.
  • Terrien’s marginal degeneration.
  • Keratoglobus.
  • Post-traumatic corneal ectasia.
  • Protrusion of cornea subsequent to corneal thinning from ulceration.

 

The distinction can usually be made by slit- lamp (bio-microscopy) examination and corneal topography.

Management should be carried out under medical supervision.

Medical therapy:

  • Spectacle correction: Initially, attempt should be made to correct myopic astigmatism by prescribing spectacle correction. Early keratoconus patients may get satisfactory vision with spectacles. Development of irregular astigmatism often limits the use of spectacle correction, and patients may require contact lenses.
  • Rigid gas- permeable (RGP) contact lenses: Rigid gas- permeable (RGP) contact lenses are often the first lenses of choice and may be prescribed once spectacle-corrected acuity becomes inadequate. Other lenses used are piggyback lenses, pure hydro gel lenses, multi curve or aspheric contact lenses. Contact lens wear often is complicated by episodes of intolerance, allergic reactions (e.g. giant papillary conjunctivitis), corneal abrasions, neovascularisation, sometimes leading to total intolerance. Though contact lenses are extremely useful, it may increase the risk of corneal scarring.

 

 

Surgical therapy:

Surgical therapy may be resorted to when patient does not improve with the use of contact lenses.

Contact lenses may fail due to:

  • Inadequate acuity.
  • Inadequate lens tolerance.
  • Frequent lens displacements.
  • Peripheral thinning.

Surgical procedures:

  • Keratoplasty: Standard surgical treatment consists of keratoplasty. Recurrence of keratoconus after keratoplasty is rare. Recurrence may be due to:

-       Incomplete excision of the cone at the time of surgery.

-       Unrecognised keratoconus in the corneal donor.

-       Host cellular activity that causes changes in the donor corneal material.

Lamellar keratoplasty: Lamellar keratoplasty is effective, but this is not preferred because of the technical difficulties in the procedure and slightly reduced visual outcome.

Epikeratoplasty: Epikeratoplasty has been successful as well, but it has been abandoned due to suboptimal visual outcome.

Penetrating keratoplasty: By far the most frequent procedure is penetrating keratoplasty. At the time of keratoplasty, decreasing the donor/ recipient size disparity reduces post-keratoplasty myopia. Complications of penetrating keratoplasty include corneal graft rejection, glaucoma, cataract formation, anisometropia, astigmatism and infection.

Deep anterior lamellar keratoplasty (DALK): Deep anterior lamellar keratoplasty (DALK) has been proposed as an alternative to penetrating keratoplasty. Recent advances in surgical technique have generated interest in DALK. Primary advantages are:

-       Increased structural integrity.

-       Reduced risk of graft rejection.

While challenging to perform, innovative techniques such as the big-bubble technique have reduced surgical operating time, improved the safety of the procedure, and gives visual outcome similar to penetrating keratoplasty. Complications of DALK include graft- host interface haze, Descemet’s membrane perforation and stromal rejection.

  • Intra-corneal ring segments: Intra-corneal ring segments have achieved some success in patients without corneal scarring in reducing the myopia and astigmatism and improving spectacle- corrected visual acuity. INTACS (Addition Technology, Fermont, CA) are intrastromal corneal ring segments, placed in the peripheral cornea, either mechanically or with the femtosecond laser.
  • Combined riboflavin-ultraviolet type A rays (UVA) collagen cross-linking: Combined riboflavin-ultraviolet type A rays (UVA) collagen cross-linking consists of photo-polymerisation of corneal stroma by combining vitamin B2 (photosensitising substance) with UVA. This process increases rigidity of corneal collagen and thus reduces the likelihood of further ectasia.

 

Prognosis:

Keratoconus, though progressive initially, stabilises after some time in most of the patient. Most patients with keratoconus do well with rigid contact lenses.

Keratoplasty may be required when patients do not improve with contact lenses.

Fortunately, patients with keratoconus never become totally blind.

Complications of keratoconus may be:

  • Acute corneal hydrops: Advanced keratoconus rarely may progress to acute corneal hydrops due to breaks in Descemet’s membrane, leading to corneal oedema.
  • Secondary corneal scarring.

 

  • To prevent keratoconus, patients should avoid rubbing of eyes.

  • PUBLISHED DATE : Jun 28, 2016
  • PUBLISHED BY : Zahid
  • CREATED / VALIDATED BY : Dr. S. C. Gupta
  • LAST UPDATED ON : Jun 28, 2016

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