Keratoconus: A review

doi:10.1016/j.clae.2010.04.006

Contact Lens and Anterior Eye

Volume 33, Issue 4, August 2010, Pages 157-166

https://doi.org/10.1016/j.clae.2010.04.006 Get rights and content

Abstract

Keratoconus is the most common primary ectasia. It usually occurs in the second decade of life and affects both genders and all ethnicities. The estimated prevalence in the general population is 54 per 100,000.

Ocular signs and symptoms vary depending on disease severity. Early forms normally go unnoticed unless corneal topography is performed. Disease progression is manifested with a loss of visual acuity which cannot be compensated for with spectacles. Corneal thinning frequently precedes ectasia. In moderate and advance cases, a hemosiderin arc or circle line, known as Fleischer's ring, is frequently seen around the cone base. Vogt's striaes, which are fine vertical lines produced by Descemet's membrane compression, is another characteristic sign. Most patients eventually develop corneal scarring. Munson's sign, a V-shape deformation of the lower eyelid in downward position; Rizzuti's sign, a bright reflection from the nasal area of the limbus when light is directed to the limbus temporal area; and breakages in Descemet's membrane causing acute stromal oedema, known as hydrops, are observed in advanced stages.

Classifications based on morphology, disease evolution, ocular signs and index-based systems of keratoconus have been proposed. Theories into the genetic, biomechanical and biochemical causes of keratoconus have been suggested. Management varies depending on disease severity. Incipient cases are managed with spectacles, mild to moderate cases with contact lenses and severe cases can be treated with keratoplasty. This article provides a review on the definition, epidemiology, clinical features, classification, histopathology, aetiology and pathogenesis, and management and treatment strategies for keratoconus.

Section snippets

Definition

Keratoconus, which was first described in detail in 1854 [1], derives from the Greek words Kerato (cornea) and Konos (cone). Keratoconus is the most common primary ectasia. It is a bilateral [2], [3] and asymmetric [4], [5] corneal degeneration characterized by localized corneal thinning which leads to protrusion of the thinned cornea. Corneal thinning normally occurs in the inferior-temporal as well as the central cornea [6], although superior localizations have also been described [7], [8].

Epidemiology

The incidence and prevalence in the general population has been estimated to be between 5 and 23, and 5.4 per 10,000, respectively [3], [9], [12]. Differences on the rates reported are attributed to different definitions and diagnostic criteria employed between studies. However, it would not be surprising to expect an increase in the incidence and prevalence rates of this disease over the next few years with the current wide spread use of corneal topography leading to improved diagnosis.

Clinical features

The ocular symptoms and signs of keratoconus vary depending on disease severity. At incipient stages, also referred to as subclinical or frustre forms, keratoconus does not normally produce any symptoms and thus can go unnoticed by the patient and practitioner unless specific tests (i.e., corneal topography) are undertaken for diagnosis [22]. Disease progression is manifested by a significant loss of visual acuity which cannot be compensated for with spectacles. Therefore, eye care

Classification

Several classifications of keratoconus based on morphology, disease evolution, ocular signs and index-based systems have been proposed in the literature:

Histopathology

Histopathologically, there are three signs which typically characterize keratoconus: (1) stromal corneal thinning; (2) Bowman's layer breakage; and (3) iron deposits within the corneal epithelium's basal layer [9], [12].

In keratoconus disease, the corneal epithelium's basal cells degenerate and grow towards Bowman's layer and this can be noted by observing accumulation of ferritin particles into and between epithelial cells [50]. Basal cell density is also decreased in comparison to normal

Aetiology and pathogenesis

Despite the intensive research activity over the last few decades into the aetiology and pathogenesis of keratoconus, the cause(s) and possible mechanisms for its development remain poorly understood. Albeit, there have been several hypotheses proposed into the genetic and biochemical mechanisms. Furthermore, the association of other diseases to keratoconus has also been investigated.

Management and treatment

Keratoconus management varies depending on the disease severity. Traditionally, incipient cases are managed with spectacles, mild to moderate cases with contact lenses, and severe cases can be treated with keratoplasty. Other surgical treatment options include intra-corneal rings segments, corneal cross-linking, laser procedures (i.e., photorefractive keratectomy, phototherapeutic keratoctomy, lasik in situ keratomileusis) intra-ocular lens implants or a combination of these.

Conclusion

Keratoconus is the most common corneal ectasia. It usually appears in the second decade of the life and affects both genders and all ethnicities. The prevalence in the general population has been estimated to be approximately 54 per 100,000. The ocular symptoms and signs of keratoconus vary depending on disease severity. Despite the intensity of research activity over the last few decades into its aetiology and pathogenesis, the cause(s) and possible mechanisms for development remain poorly

Conflict of interest

MR-J and JSW report no conflicts of interest. JS-R is a full-time employee of Menicon Company Limited.

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Effect of keratoplasty on the quality of life of keratoconus patients
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Les déformations cornéennes causées par le kératocône produisent des aberrations optiques (AO) de haut degré. Malgré une correction optique adaptée elles altèrent la qualité de la vision et diminuent la qualité de vie des patients ; d’autant plus que la population touchée est majoritairement jeune et en âge de travailler. Lorsque l’amincissement est trop important ou la transparence cornéenne trop atteinte une greffe de cornée peut être proposée. Dans cette étude nous allons comparer la qualité de vie de patients atteints de kératocône à des stades précoces (stades 1 et 2) ou avancés (stades 3 et 4) de la classification de Krumeich ainsi que des patients ayant eu un kératocône traité par kératoplastie. La qualité de vie a été évaluée grâce au questionnaire NEI-VFQ 25 qui est validé pour le kératocône. Un examen aberrométrique (OQAS® ; HD Analyser, Visiometrics, Terrassa, Espagne) a aussi été réalisé pour évaluer la qualité de vision des patients. Nos résultats montrent que la kératoplastie permet d’obtenir une amélioration de la qualité de vie par rapport aux kératocônes de stades avancés dans les domaines des activités en vision de loin (p = 0,0083) et de près (p = 0,029). Cette amélioration concerne aussi la meilleure acuité visuelle corrigée (MAVC) (p = 0,032) et la transparence des milieux (OSI) (p = 0,049). Notre étude montre que la kératoplastie permet d’améliorer la transparence cornéenne et il est intéressant de noter qu’elle permet d’améliorer sur le long terme la qualité de vie des patients.
Corneal deformations caused by keratoconus produce high levels of optical aberration (OA). Despite appropriate optical correction, these alter the quality of vision and diminish the patient's quality of life, especially since the affected population is predominantly young and of working age. When thinning is too severe or corneal transparency too impaired, a corneal transplant may be considered. In this study, we compare the quality of life of patients with keratoconus in the early (stages 1 and 2) or advanced (stages 3 and 4) stages of the Krumeich classification, as well as patients who have had keratoconus treated by keratoplasty. Quality of life was assessed using the NEI-VFQ 25 questionnaire, the most widely used for keratoconus. An aberrometric examination (OQAS®; HD Analyser, Visiometrics, Terrassa, Spain) was also performed to assess patients’ quality of vision. Our results show that keratoplasty provides an improvement in quality of life compared with advanced-stage keratoconus in the areas of distance (p = 0.0083) and near vision (p = 0.029) activities. This improvement also applies to Best-Corrected Visual Acuity (BCVA) (p = 0.032) and transparency (OSI) (p = 0.049). Our study shows that keratoplasty improves corneal transparency, and it is interesting to note that it improves patients’ quality of life over the long term.
RiTe conjugate mediated corneal collagen crosslinking, a novel therapeutic intervention for keratoconus – in vitro and in vivo study
2024, International Journal of Pharmaceutics
Corneal collagen crosslinking (CXL) is an effective method to halt the disease progression of keratoconus, a progressive corneal dystrophy leading to cone shaped cornea. Despite the efficacy of standard protocol, the concerning step of this procedure is epithelial debridement performed to facilitate the entry of riboflavin drug. Riboflavin, a key molecule in CXL protocol, is a sparsely permeable hydrophilic drug in corneal tissues. The present study has employed cell penetrating peptide (CPP), Tat₂, to enhance the penetration of riboflavin molecule, and thereby improve currently followed CXL protocol. This study demonstrates approximately two-fold enhanced uptake of CPP riboflavin conjugate, Tat₂riboflavin-5′Phosphate (RiTe conjugate), both in vitro and in vivo. Two different CXL protocols (Epi ON and Epi OFF) have been introduced and implemented in rabbit corneas using RiTe conjugate in the present study. The standard and RiTe conjugate mediated CXL procedures exhibited an equivalent extent of crosslinking in both the methods. Reduced keratocyte loss and no endothelial damage in RiTe conjugate mediated CXL further ascertains the safety of the proposed CXL protocols. Therefore, RiTe conjugate mediated CXL protocols present as potential alternatives to the standard keratoconus treatment in providing equally effective, less invasive and patient compliant treatment modality.
Air-puff induced corneal dynamics in normal, forme fruste and keratoconic eyes measured with OCT-based optical biometry
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The aim of this study was to characterize corneal dynamic response in normal subjects (NL), patients with forme fruste keratoconus (FFKC) and patients with clinical keratoconus (KC) using air-puff OCT-based optical biometry. This cross-sectional study included 50 normal eyes (NL), 15 forme fruste eyes (FFKC) and 31 eyes with early and moderate keratoconus (KC). Keratometry and pachymetry were performed with MS-39 (CSO, Italy). The dynamic response of the corneal apex to air-puff stimulus was imaged with an optical biometer combined with the air-puff system allowing correction for whole eye retraction. The amplitude and duration of corneal displacement, the maximum velocity of the cornea during loading and recovery and hysteresis loop area were extracted from the data. The differences between NL, FFKC and KC groups were tested and the correlation between extracted biomechanical parameters and age, intraocular pressure (IOP) or corneal geometry was assessed for each group. Maximum corneal displacement was higher in the KC eyes than in the NL eyes (p < 0.001), corneal response was longer and maximum velocity of corneal apex was higher in KC eyes (p < 0.05). No significant difference in extracted parameters was detected between FFKC and NL eyes. The parameters of corneal biomechanical response depended mostly on IOP and corneal thickness in NL eyes. Weaker correlation patterns were found in KC and FFKC eyes. High-speed optical biometry combined with an air-puff stimulation allows for the evaluation of the corneal biomechanics. Keratoconus affects corneal biomechanics but the parameters measured could not effectively distinguish forme fruste keratoconus from normal eyes.
Bowman Layer Onlay Grafting as a Minimally Invasive Treatment for the Most Challenging Cases in Keratoconus
2024, American Journal of Ophthalmology
To analyze the clinical outcomes after Bowman layer (BL) onlay grafting for the treatment of progressive, advanced keratoconus.
Prospective, interventional case series.
Twenty-one eyes underwent BL onlay grafting. After removing the epithelium, a single or double BL graft was “stretched” onto the corneal surface, allowed to dry-in, and a soft bandage lens was placed until the graft was re-epithelialized. Best spectacle- and/or best contact lens–corrected visual acuity (BSCVA/BCLVA), corneal tomography, and postoperative complication rates were analyzed for the total group and 2 subgroups (group 1: preoperative maximum keratometry [Kmax] <69 diopters [D; n = 7); group 2: preoperative Kmax ≥69 D [n = 14]). Follow-up ranged from 6 to 36 months (mean 21 ± 11 months).
All 21 surgeries were uneventful. Overall, Kmax changed from 76 ± 12 D preoperatively to 72 ± 9 D at 6 to 36 months postoperatively (P = .015). Kmax decreased by 6 D in group 2 (P = .002) but did not change in group 1. Average BSCVA remained stable for group 1 and improved from preoperatively 0.8 ± 0.4 to 0.4 ± 0.2 logarithm of the minimum angle of resolution postoperatively in group 2 (P = .032); BCLVA remained stable (P > .05). Within the first postoperative weeks, 2 eyes required BL graft repositioning after inadvertent bandage lens removal and 4 eyes underwent BL retransplantation for incomplete re-epithelialization. One eye underwent BL regrafting 12 months postoperatively after traumatic corneal erosion. All eyes showed a completely re-epithelialized graft at the last available follow-up.
BL onlay grafting is a completely extraocular, minimally invasive surgical technique, providing up to −6 D of corneal flattening in eyes with advanced progressive keratoconus, allowing for continued (scleral) contact lens wear and therefore preserving the BCLVA.
Improving early detection of keratoconus by Non Contact Tonometry. A computational study and new biomarkers proposal
2024, Journal of the Mechanical Behavior of Biomedical Materials
Keratoconus is a progressive ocular disorder affecting the corneal tissue, leading to irregular astigmatism and decreased visual acuity. The architectural organization of corneal tissue is altered in keratoconus, however, data from ex vivo testing of biomechanical properties of keratoconic corneas are limited and it is unclear how their results relate to true mechanical properties in vivo. This study explores the mechanical properties of keratoconic corneas through numerical simulations of non-contact tonometry (NCT) reproducing the clinical test of the Corvis ST device. Three sensitivity analyses were conducted to assess the impact of corneal material properties, size, and location of the pathological area on NCT results. Additionally, novel asymmetry-based indices were proposed to better characterize corneal deformations and improve the diagnosis of keratoconus. Our results show that the weakening of corneal material properties leads to increased deformation amplitude and altered biomechanical response. Furthermore, asymmetry indices offer valuable information for locating the pathological tissue. These findings suggest that adjusting the Corvis ST operation, such as a camera rotation, could enhance keratoconus detection and provide insights into the relative position of the affected area. Future research could explore the application of these indices in detecting early-stage keratoconus and assessing the fellow eye’s risk for developing the pathology.
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The pre-Descemet's layer/Dua's layer, also termed the Dua-Fine layer and the pre-posterior limiting lamina layer, lies anterior to the Descemet's membrane in the cornea, is 10 μm (range 6–16) thick, made predominantly of type I and some type VI collagen with abundant elastin, more than any other layer of the cornea. It has high tensile strength (bursting pressure up to 700 mm of Hg), is impervious to air and almost acellular. At the periphery it demonstrates fenestrations and ramifies to become the core of the trabecular meshwork, with implications for intraocular pressure and glaucoma. It has been demonstrated in some species of animals.
The layer has assumed considerable importance in anterior and posterior lamellar corneal transplant surgery by improving our understanding of the behaviour of corneal tissue during these procedures, improved techniques and made the surgery safer with better outcomes. It has led to the innovation of new surgical procedures namely, pre-Descemet's endothelial keratoplasty, suture management of acute hydrops, DALK-triple and Fogla's mini DALK.
The discovery and knowledge of the layer has introduced paradigm shifts in our age old concepts of Descemet's membrane detachment, acute corneal hydrops in keratoconus and Descemetoceles, with impact on management approaches. It has been shown to contribute to the pathology and clinical signs observed in corneal infections and some corneal dystrophies. Early evidence suggests that it may have a role in the pathogenesis of keratoconus in relation to its elastin content. Its contribution to corneal biomechanics and glaucoma are subjects of current investigations.

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ReviewKeratoconus: A review

Abstract

Section snippets

Definition

Epidemiology

Clinical features

Classification

Histopathology

Aetiology and pathogenesis

Management and treatment

Conclusion

Conflict of interest

Am J Ophthalmol

J Cataract Refract Surg

Contact Lens Anterior Eye

Surv Ophthalmol

Surv Ophthalmol

Ophthalmology

Contact Lens Anterior Eye

Ophthalmology

Contact Lens Anterior Eye

Ophthalmology

Ophthalmology

J Cataract Refract Surg

Ophthalmology

Contact Lens Anterior Eye

J Cataract Refract Surg

J Cataract Refract Surg

Ophthalmology

Ophthalmology

Contact Lens Anterior Eye

J Cataract Refract Surg

J Fr Ophtalmol

Genet Med

J Allergy Clin Immunol

Am J Ophthalmol

Practical observations on conical cornea

Biomicroscopic signs and disease severity in keratoconus

Cornea

Between-eye asymmetry in keratoconus

Cornea

Between eye asymmetry in keratoconus in an Indian population

Clin Exp Optom

Superior keratoconus

Cornea

An unusual case of keratoconus

J Pediatr Ophthalmol Strabismus

Longitudinal analysis of the fellow eyes in unilateral keratoconus

Invest Ophthalmol Vis Sci

The ophthalmic assistant: a text for allied and associated ophthalmic personnel

A profile of keratoconus in New Zealand

Cornea

Referral patterns, treatment management and visual outcome in keratoconus

Eye

Does ethnic origin influence the incidence or severity of keratoconus?

Eye

The Dundee university Scottish Keratoconus study: demographics, corneal signs, associated diseases, and eye rubbing

Eye

Topographic indications of emerging keratoconus in teenage New Zealanders

Cornea

Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asians and white patients

Eye

Subclinical keratoconus diagnosis by elevation topography

Arch Soc Esp Oftalmol

Über Keratoconus und eigenartige Pigmenfbildung in der kornea

München Med Wschr

Transitient rigid lens-induced striae in keratoconus

Optom Vis Sci

Manual of contact lens prescribing and fitting

A new method for grading the severity of keratoconus: the keratoconus severity score (KSS)

Cornea

The spectrum of topography found in keratoconus

CLAO J

A novel topographic pattern in some keratoconus suspects

Ophthalmology

Le keratocone fruste au javal

Ophtalmologica

Keratocone classique et keratocone fruste, arguments unitaires

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Review
Keratoconus: A review