[Keratoconus: main lines of research]. / Keratokonus: osnovnye napravleniya issledovanii.

Keratoconus (KC) research focuses on studying pathogenesis, advancing diagnostic techniques and methods of correction and treatment. The working hypothesis for KC etiopathogenesis is based on abnormalities in distribution of microelements in the cornea and its potential influence on the processes of stromal collagen disorganization. Improvement of early diagnosis of KC is associated with evaluation of microstructural changes in the cornea using computerized methods such as Scheimpflug camera and high-definition optical methods for visualization of initial signs of a pigment ring. The main optimization directions of KC contact correction are associated with increasing gas permeability of the material, improving lens design and methods of lens fitting. Customized fitting of gas-permeable scleral hard contact lenses with consideration of topographic features of the anterior corneal surface allows achieving stable lens positioning and preserving the tear gap between the lens and the cornea. Alternative methods of correcting the refraction component of KC are associated with surgical interventions involving increase in corneal volume in the paracentral area. Implantation of corneal ring segments should be considered as an alternative to correction of refractive errors in cases with unsatisfactory individual subjective tolerance and insufficient patient compliance with contact correction. Femtolaser-assisted implantation of intrastromal allotransplants along with a decrease in the degree of spherical and astigmatic components of refractive errors contribute to prevention of KC progression. Advancement of techniques of corneal collagen cross-linking for prevention of KC progression is aimed at reducing the risk of developing post-operative complications directly related to the extent of intraoperative deepithelization. Limiting corneal ectatic area by implantation of intrastromal allotransplants can be considered an alternative approach. Deep anterior lamellar keratoplasty and penetrating keratoplasty are the surgeries of choice in replacing altered corneal layers in KC. With regard to the modern trends in selective keratoplasty, selective replacement of the cornea in lamellar keratoplasty reduces the rate of injuries and the risk of tissue reaction.

Comprehensive management of post-LASIK ectasia: From prevention to treatment.

Post-laser in situ keratomileusis (post-LASIK) ectasia (PLE) is one of the most serious complications after refractive surgery, mainly manifested as progressive thinning and trembling thinning of the cornea, accompanied by increased myopia and astigmatism. The mechanisms behind mainly include genetic risk factors and external environmental factors such as eye rubbing and cornea surgery. In order to achieve the goal of reducing the incidence of ectasia, preoperative screening strategies need to be continuously improved, through the collection and assessment of genetic and environmental risk factors. Although previous preoperative screening methods did not have a uniform standard, the emergence of artificial intelligence (AI) can help us process a large amount of information and make rational use of the data. By using high-fidelity finite element modelling, differences in preoperative and postoperative strain distributions can be observed, which can predict the risk of postoperative ectasia. In this review, we describe the incidence, aetiology, prevention and treatment of PLE for the purpose of comprehensive management. In terms of treatment, corneal collagen cross-linking has been widely used to treat progressive keratoconus and other ectasia disease, either as a preventive measure during surgery or as a therapeutic modality after surgery to prevent progression of corneal dilation. Although the standard Dresden protocol has been identified as the gold standard treatment for corneal dilatation, a series of refinements, investigations and long-term studies have been conducted in recent years. Thus, understanding the factors involved in delaying the onset and slowing progression of cornea ectasia will be key to reducing the incidence worldwide.

Advanced Research in Scleral Cross-Linking to Prevent From Progressive Myopia.

ABSTRACT: Riboflavin-ultraviolet A (UVA) collagen cross-linking (CXL) has been applied in clinical settings to prevent the progression of keratoconus and corneal dilatation caused by other reasons in past decades. As CXL with riboflavin-UVA can enhance the stiffness of collagen-rich tissues, this technique has been further used on sclera to investigate as a safe and effective myopia prevention treatment. Despite the riboflavin-UVA scleral CXL is still in the animal and in vitro experimental phases and the mechanism is not very clear, it is promising to control myopia development clinically. In this article, researches on the laboratory experiments of riboflavin-UVA scleral CXL on scheme exploration and mechanism were reviewed in order to provide more laboratory evidence for scleral CXL in clinical myopia prevention and control in the future.

Inducing fibrogenesis and new interfibrillary bonds in post-laser in situ keratomileusis keratectasia.

Flap creation weakens the cornea and is a risk factor for keratectasia after laser in situ keratomileusis (LASIK). We describe a new technique to halt the progression of keratectasia by mechanically reintegrating the flap into the residual stroma. Deep stromal vertical puncturing is performed in the 4.0 to 9.0 mm paracentral corneal zone at a depth of 350 to 420 µm. The puncturing is applied in circumferential rows using a 25-gauge needle or a diamond blade, with denser puncturing at the level of the cone. In 5 eyes with worsening post-LASIK keratectasia, improved uncorrected and corrected visual acuities, corneal flattening, and a hyperopic shift were observed. There was no progression of keratectasia on serial topographies. New collagen fibrogenesis was documented by optical coherence tomography. The technique seems to be promising to halt the progression of post-LASIK keratectasia. More clinical data and longer follow-up are needed for validation.

Posterior keratoconus.

Posterior keratoconus (PKC) is a rare, typically non-inflammatory condition that is characterised by an abnormal posterior corneal curvature, which may be accompanied by overlying stromal opacification. It is usually congenital and can be associated with other ocular and systemic abnormalities. PKC remains a clinical diagnosis, although imaging techniques including ultrasound biomicroscopy and anterior segment optical coherence tomography may be useful tools for confirmation and classification. Genetic studies should be considered, although no specific genetic defects have been identified thus far. As a potential cause of amblyopia, early diagnosis and management are crucial in maximising visual potential. Occasionally, management considerations may also include surgical intervention, such as corneal transplantation. Intraocular lens power calculation at the time of cataract surgery requires special consideration. Here, we review the present literature on PKC and consider future directions in the management of this rare entity.

Biomechanical Strengthening of the Human Cornea Induced by Nanoplatform-Based Transepithelial Riboflavin/UV-A Corneal Cross-Linking.

Purpose: The purpose of this study was to investigate the biomechanical stiffening effect induced by nanoplatform-based transepithelial riboflavin/UV-A cross-linking protocol using atomic force microscopy (AFM). Methods: Twelve eye bank donor human sclerocorneal tissues were investigated using a commercial atomic force microscope operated in force spectroscopy mode. Four specimens underwent transepithelial corneal cross-linking using a hypotonic solution of 0.1% riboflavin with biodegradable polymeric nanoparticles of 2-hydroxypropyl-ß-cyclodextrin plus enhancers (trometamol and ethylenediaminetetraacetic acid) and UV-A irradiation with a 10 mW/cm2 device for 9 minutes. After treatment, the corneal epithelium was removed using the Amoils brush, and the Young's modulus of the most anterior stroma was quantified as a function of scan rate by AFM. The results were compared with those collected from four specimens that underwent conventional riboflavin/UV-A corneal cross-linking and four untreated specimens. Results: The average Young's modulus of the most anterior stroma after the nanoplatform-based transepithelial and conventional riboflavin/UV-A corneal cross-linking treatments was 2.5 times (P < 0.001) and 1.7 times (P < 0.001) greater than untreated controls respectively. The anterior stromal stiffness was significantly different between the two corneal cross-linking procedures (P < 0.001). The indentation depth decreased after corneal cross-linking treatments, ranging from an average of 2.4 ± 0.3 µm in untreated samples to an average of 1.2 ± 0.1 µm and 1.8 ± 0.1 µm after nanoplatform-based transepithelial and conventional cross-linking, respectively. Conclusions: The present nanotechnology-based transepithelial riboflavin/UV-A corneal cross-linking was effective to improve the biomechanical strength of the most anterior stroma of the human cornea.

Corneal Cross-Linking: An Example of Photoinduced Polymerization as a Treatment Modality in Keratoconus.

The cornea is one of the principal refractive elements in the human eye and plays a crucial role in the process of vision. Keratoconus is the most common corneal dystrophy, found mostly among young adults. It is characterized by a reduced number of collagen cross-links in the corneal stroma, resulting in reduced biomechanical stability and an abnormal shape of the cornea. These changes lead to progressive myopia, corneal thinning, central scarring and irregular astigmatism, causing severely impaired vision. Hard contact lenses, photorefractive keratectomy or intracorneal rings are the most common treatment options for refractive error caused by keratoconus. However, these techniques do not treat the underlying cause of the corneal ectasia and therefore are not able to stop the progression of the disease. Riboflavin photoinduced polymerization of corneal collagen, also known as corneal cross-linking (CXL), has been introduced as the first therapy which, by stabilizing the structure of the cornea, prevents the progression of keratoconus. It stiffens the cornea using the photo-sensitizer riboflavin in combination with ultraviolet irradiation. This is a current review of the CXL procedure as a therapy for keratoconus, which relies on photoinduced polymerization of human tissue. We have focused on its biomechanical and physiological influences on the human cornea and have reviewed the previous and current biochemical theories behind cross-linking reactions in the cornea.

Stiffening effects of riboflavin/UVA corneal collagen cross-linking is hydration dependent.

The collagen cross-linking is a relatively new treatment option for strengthening the cornea, delaying, and in some cases stopping the progression of keratoconus. The uniaxial tensile experiments are among the most commonly used techniques to assess the effectiveness of this therapeutic option in enhancing tensile properties. In the present study, we investigated the possible effects of hydration on stiffening effects of corneal collagen cross-linking procedure, as measured by the uniaxial tensile testing method. For this purpose, after cross-linking bovine corneas, we let the strips to dehydrate in air or swell in a solution until their thickness reached an average thickness of 0.5, 0.7, 0.9, 1.1, and 1.5 mm. Using thickness as a representative of hydration, we divided corneal strips into five different groups and measured their stress-strain behavior by conducting uniaxial tensile experiments in mineral oil. It was observed that the collagen cross-linking treatment and hydration together affect the tensile behavior of the bovine cornea. While corneal collagen cross-linking resulted in a significant increase in the tensile stress-strain response of each thickness group (P<0.01), less hydrated collagen cross-linked samples showed a significantly stiffer response (P<0.01). A master curve was found for representing the tensile behavior of the collagen cross-linked bovine cornea at different levels of hydration. The results of the present research confirmed that the amount of mechanical stiffening of the corneal collagen cross-linking, as measured by uniaxial tensile testing, strongly depends on the hydration. Therefore, it is concluded that uniaxial tensile experiments could only be used to assess stiffening effects of the collagen cross-linking treatment if the hydration of specimens is fully controlled.

Association between diabetes and keratoconus: a case-control study.

PURPOSE: To compare the prevalence and association of diabetes mellitus (DM) between keratoconus (KC) and non-KC populations and evaluate whether DM has the potential to protect the cornea against developing keratectasia. METHODS: A retrospective case-control study was conducted on 1383 KC patients and 1383 non-KC controls. The presence or absence of either type 1 or type 2 DM was investigated in both groups. Statistical significance and odds ratios were calculated. RESULTS: The prevalence of DM in KC patients and the control group was 0.8% and 2.2%, respectively. Statistical analysis revealed a strong protective effect of DM against KC (odds ratio = 0.350, P = 0.001). This effect was only seen in type 2 DM patients (odds ratio = 0.079, P < 0.001) and not in patients with type 1 DM (odds ratio = 3.013, P = 0.073). CONCLUSIONS: The results of this study suggest that DM provides a statistically significant protective effect against the development of KC. This investigation showed that the biomechanical effects of cross-linking were also reflected in epidemiological results.

[The effectiveness of corneal cross-linking in stopping the progression of keratoconus]. / Efektivita corneal cross-linkingu v zastavení progresie keratokónusu.

OBJECTIVE: Objective of the study was to prove the efficiency of corneal cross-linking (CXL) in stopping the progression of keratoconus. METHODS: In this study were included 58 eyes of patients with progressive keratoconus who underwent CXL according to the Dresden protocol in the years 2007-2009 at the Ophthalmic clinic FN Brno Bohunice. The eyes of patients were divided into four groups according to the change of maximum curvature of the cornea two years after CXL. RESULTS: Stabilization of maximum curvature of the cornea have been reported in 40 % of eyes, regression in 57 % of eyes by an average of 1,92D and disease progression in 3 % of eyes 2 years after CXL. The eyes with regression over 2D had significantly higher best-corrected visual acuity before and after the procedure compared to the group with stabilization. Spherical equivalent increased significantly in all groups, on average, in the group with stabilization of 0,54D, in the group with mild regression of 0,71D and in the group with a large regression of 2,09D. In the group with a large regression 100 % of eyes had stabilization or increase in SE. Our observations showed that, when a decrease in the patient keratometric values of cornea is present after CXL, it is comprehensive and applies to all parameters. CONCLUSION: We have confirmed that corneal cross-linking stops the progression of the disease in 97 % of eyes two years after the procedure.

Research progress in corneal cross-linking agents.

Corneal collagen cross-linking with UVA-riboflavin is currently the only method for preventing the progression of keratoconus from the pathological perspective. Topical application of a direct cross-linking agent is now attracting widespread attention in clinical settings. This article reviews the research progress in the application of indirect or direct cross-linking agents (e.g., riboflavin, glucose, ribose, glutaraldehyde, formaldehyde, glyceraldehyde, short chain aliphatic ß-nitro alcohol, and genipin) in the treatment of corneal diseases and analyzes the cross-linking efficacy, toxicity, and merits and disadvantages of each cross-linking agent, providing clinical information for further studies.

[Detection of early forms of keratoconus - current screening methods]. / Früherkennung des Keratokonus - systemassistierte Screening-Verfahren heute.

The detection of early forms of keratoconus is still a challenge for clinicians. Beside clinical examination and diagnosis of keratoconus, a series of examination techniques has been established in clinical routine to assist in the diagnosis of early forms of keratoconus: corneal topography for measuring the geometry of the corneal front surface, tomography for measuring the geometry of structures of the anterior segment of the eye, aberrometers for evaluation of optical aberrations of the entire eye, and a system for investigation of the biomechanical properties of the cornea. These instruments provide software tools which are designed for diagnostic support in keratoconus. In this review article, we provide an overview over the spectrum of measurement systems currently on the market focussing on their performance for detecting (early forms of) keratoconus. In detail, we focus on dedicated keratoconus screening software modules of topography, tomography, aberrometry and biomechanics.

[Changes of ocular higher order aberration in keratoconus eyes wearing rigid gas-permeable contact lens].

OBJECTIVE: To compare the wavefront characteristics of normal and keratoconus eyes with and without rigid gas-permeable contact lens (RGPCL), and to evaluate the visual quality in keratoconus eyes corrected by RGPCL. METHODS: Retrospective study. Higher order aberrations (HOAs) of 90 eyes in 56 keratoconus patients and 30 eyes of 17 subjects with refractive errors were quantified with a Bausch&Lomb Zywave Wavefront Analyzer. The keratoconus eyes were divided into mild (28 eyes), moderate (33 eyes) and severe (29 eyes) groups. Zernike's polynomial was used to describe the wavefront measurements. Root mean square (RMS) values of the total HOAs, S3, S4, S5, total coma (T. Coma) and total spherical aberrations (T. Sph) were obtained in the same eye with and without contact lenses. We used paired sample t-test and independent-samples t-test to analyze the data. RESULTS: Mean RMS values for High (F = 72.12, P(1) = 0.00), S3 (F = 68.15, P = 0.00), S4 (F = 24.95, P(1) = 0.00), T. Coma (F = 44.67, P = 0.00), T. Sph (F = 28.90, P = 0.01) increased significantly from mild to sever keratoconus eyes RMS values of the total HOAs (t = 4.83), S3 (t = 4.39), total coma (t = 3.71) of refractive error eyes decreased significantly after fitting with RGPCL (P < 0.05). RMS values of the total HOAs (t = 8.27), S3 (t = 8.14), S4 (t = 2.29), total coma (t = 4.38) of mild keratoconus eyes decreased significantly after fitting with RGPCL (P < 0.05) RMS values of the total HOAs (t = 8.03), S3 (t = 7.22), s4 (t = 4.38), S5 (t = 4.53), total coma (t = 5.26) and total spherical (t = 2.77) of moderate keratoconus eyes decreased significantly after fitting with RGPCL (P < 0.05). Every high front-wave aberration of mild keratoconus eyes decreased to refractive error eyes'level after RGPCL fitting. Moderate (t(HOAs) = 0.63, t(s3) = 0.31, t(s4) = 1.70, t(s5) = 0.95, t(coma) = 0.06, t(spherical) = 1.99) and sever keratoconus eyes' higher order aberrations decreased significantly after RGPCL fitting (t(HOAs) = 7.50, t(s3) = 5.25, t(s4) = 5.50, t(s5) = 3.02, t(coma) = 5.90, t(spherical) = 4.60), but they still degrade compared with refractive error eyes (P < 0.05). CONCLUSIONS: RGPCL could reduce high aberrations and improve optical quality in keratoconus eyes. But the visual performance in moderate and severe keratoconus eyes with a RGPCLs is still poorer than that of normal eyes even if the corrected visual acuity is good.

[Keratectasia after refractive surgery]. / Keratektasie nach refraktiver Chirurgie.

BACKGROUND: Refractive surgery has become more and more popular in the past years. One of the most severe complications is iatrogenic keratectasia. The purpose of this article is to review the current knowledge about iatrogenic keratectasia. METHOD. A literature research (Medline) using the key words keratectasia, complication after refractive surgery and cross-linking was carried out. Apart from this, our own data from partially unpublished studies have been used. RESULTS: Since the first publication of keratectasia in 1998 more and more cases of keratectasia have been published. The main risk factor is a preoperative irregular topography. But also thin corneas, deep ablations, thin residual stromal beds and young patients age at the time of the laser surgery are further risk factors. DISCUSSION: Although preoperative examinations before refractive surgery are becoming more and more accurate and the inclusion criteria for laser ablation have become stricter, iatrogenic keratectasia still occurs. Therefore longer follow-up visits should be performed over a longer period to diagnose keratectasia in an early stage and to provide therapy.

[Keratoconus]. / Sarveiskalvon kartiorappeuman uudet hoitomahdollisuudet.

Clinical manifestations of keratoconus include reduced visual acuity, increased astigmatism, thinning of the cornea and protrusion of the cornea, as observed in the shape of the corneal surface. Spectacles are utilized in the treatment of early keratoconus, whereas hard contact lenses or intracorneal support rings are used in more advanced forms of the disease. A corneal transplant operation is applied to a far-advanced keratoconus. Photohardening of the cornea may serve as a suitable preventive treatment.

Behaviour modification in the management of chronic habits of abnormal eye rubbing.

OBJECTIVES: To describe how and why many keratoconus patients do not comply with strong advice to control chronic habits of abnormal rubbing. To outline a behaviour modification approach for controlling chronic habits of abnormal rubbing. METHODS: Common reasons for chronic habits of abnormal rubbing have been reviewed as a basis for specifying a behavioural modification approach to habit reversal. RESULTS: The methods described are organized into the classic behavioural modification structure of: (1) habit awareness, (2) competing responses, (3) development of motivation, and (4) social support. This structure is supported by the application of social influence principles to achieve optimum compliance. CONCLUSIONS: The use of take-home written information in the form of an Abnormal Rubbing Guide is the basis for the development of motivation. Family social support is based upon a widening of the responsibility for avoiding eye rubbing to all family members. Some patients will need minimal application of these principles with patient education being sufficient intervention to achieve habit reversal. For patients with strong provocation to rubbing and/or by having a well established rubbing habit, a greater exposure to the habit reversal program described is indicated. Successful habit reversal may slow the rate of ectasia progression. Prophylactic application of the methods described for patients who are at risk for developing keratoconus, or post-laser assisted in situ keratomileusis keratectasia, may show that some forms of keratectasia are preventable.

Management of chronic habits of abnormal eye rubbing.

A review of the provocations and the consequences of chronic habits of abnormal rubbing indicates a range of possible adverse responses. Gentle rubbing may double intraocular pressure. However, the combination of tight eye closure and forceful rubbing may raise intraocular pressure to more than 10 times normal levels. The possibility that, in susceptible individuals, chronic habits of abnormal rubbing may lead to the development or progression of keratoconus has been extended to the possibility of rubbing related adverse responses in other diseases and conditions. The adverse consequences of rubbing appear to be active processes, in contrast to the apparent passive nature of any recovery from those responses. Avoidance of the possibility of permanent adverse changes is clearly preferable. However, advice to avoid rubbing may not be successfully followed. Education and counseling appear to be the foundations for helping patients to control chronic habits of abnormal rubbing. An instrument has been developed as the basis for patient education and counseling for this purpose. It is intended as a take-home document which might have relevance to other family members. The widening of the application of this form of patient education to all members of a family, and a wider range of conditions, may produce beneficial synergy with advantage to patients who may have the most to gain from controlling chronic habits of abnormal rubbing.