Keratoconic Corneas Research Articles

English

We present in this paper the quantification of the geometrical features of the anterior segment of the eye using Anterior Segment Optical Coherence Tomography (AS-OCT). This quantification was achieved by following our own developed methodology including the device development and their distortion calibration (Fan and refraction) for 3-D imaging, and automatic analysis tools as well. The stastistical comparison of the corrected topographies of the anterior cornea with topographies from state-of-the art clinical topography systems represents a valuable contribution toward the development All-OCT-based topographic systems. In addition, we first reported topographies of the crystalline lens in vivo, which is a promising tool to investigate the lens optical properties, the contribution of the lens to the overall retinal image quality, and understanding the change of the physical properties of the lens with accommodation and aging. Furthermore, our quantitative AS-OCT allowed the analysis of the keratoconic cornea and the changes produced by Intra Corneal Ring Segment (ICRS) treatment, as well as monitoring of the ICRS 3-D location. Finally, OCT-based biometry we present in this paper is a promising tool to investigate the changes after cataract surgery; the contribution of the (Intra Ocular Lens) IOL location and tilt to the overall retinal image quality, and in the design of new IOLs.

The clinical study of corneal cross-linking with hypo-osmolar riboflavin solution in thin keratoconic corneas

To evaluate the clinical results of keratoconic eyes with thin corneas that were treated by using corneal collagen cross-linking with hypo-osmolar riboflavin solution. Retrospective, nonrandomized study. Fifteen eyes of 15 patients with progressive keratoconus and corneal thickness of less than 400 µm (without the epithelium) were included in this study. Application of hypo-osmolar riboflavin solution to the cornea for 30 minutes after its de-epithelialization was followed by ultraviolet A collagen cross-linking. Corneal thickness was measured with anterior segment OCT before surgery, after epithelial removal, and after hypotonic riboflavin solution application. Before the ultraviolet A application was started, we must be sure that the thinnest cornea was equal to or greater than 400 µm. Examinations comprised an evaluation of uncorrected distance visual acuity and best corrected visual acuity, slit-lamp microscopy, corneal topography, and endothelial cell counting after the procedure. Before surgery, the mean corneal thickness (with the epithelium) was (399.27 ± 17.87) µm, and after the removal of epithelium, the thickness of the cornea was reduced to (354.00 ± 18.57) µm. After the application of the hypo-osmolar riboflavin solution, this value increased to (477.73 ± 20.87) µm. The improvements in visual acuity and keratometry readings occurred during the follow-up. No statistically signiflcant differences were found between preoperative and postoperative endothelial cell counts. No complications such as scarring lesions in the stroma and corneal endothelial damage were observed throughout the study period. The results of our study, using hypo-osmolar riboflavin solution in a cross-linking procedure in thin corneas, show a stability of keratoconus 12 months after cross-linking.

Expression of HGF/c‐Met in control and keratoconus corneas

AbstractPurpose Keratoconus (KC) is the most common primary degenerative corneal disease with a prevalence of around 1 in 2000 worldwide. A recent genome‐wide association study on potential genes associated with KC identified a significant association between KC and two single nucleotide polymorphisms in the promoter region of the HGF gene. The HGF/c‐Met pathway protects cells from apoptosis and is important to maintain epithelial homeostasis. In this study, we investigated if the HGF/c‐Met pathway is involved in KC by comparing HGF/c‐Met protein expression in control and KC samples.Methods HGF and c‐Met immunoreactivities in control (n=5) and KC (n=10) corneas were imaged by confocal microscopy.Basal tears were collected by capillary micropipettes from control and KC patients (n=5 each), and HGF protein expression determined by Western blot. Intracellular c‐Met (the membrane bound receptor for HGF) expression was detected by extracting proteins from both control and KC corneal epithelium (n=5 each) followed by Western blot.Results HGF and c‐Met were expressed in control and KC corneas. However,in KC obvious cytoplasmic staining of basal epithelium was noted compared to the more diffuse cytoplasmic epithelial immunostaining in control corneas. Western blot results showed that lower levels of HGF in KC tears compared to control tears, and the intracellular c‐Met expression was also weaker in KC cell lysates compared to controls.Conclusion We find that HGF/c‐met expression patterns were altered between KC and control corneas, and their expression levels were reduced in KC tears and corneal epithelium cell lysates suggesting a role for this pathway in the pathogenesis of KC. Funding: Medical School of Sydney University, Sydney Eye Hospital Foundation, Lions NSW Eye Bank

Beneficial effect of the antioxidant riboflavin on gene expression of extracellular matrix elements, antioxidants and oxidases in keratoconic stromal cells

BackgroundKeratoconus manifests as a conical protrusion of the cornea and is characterised by stromal thinning. This causes debilitating visual impairment which may necessitate corneal transplantation. Therapeutic targets related to disease mechanisms are currently lacking, as the pathobiology remains unclear. Many pathological features may be manifestations of defects in wound healing and reactive oxygen species (ROS)‐associated functions. In a wide range of tissue and cell types, antioxidant exposure has beneficial effects on both of these pathways. This study investigated the effect of treatment with the antioxidant riboflavin on wound healing and ROS‐associated functions in keratoconus.MethodsStromal cells were isolated from human central keratoconic (n = 3) and normal (n = 3) corneas. Total RNA was extracted and reverse‐transcribed into complementary DNA. The gene expression of 22 genes involved in repair (eight normal and four repair‐type extracellular matrix constituents) and ROS‐associated processes (eight antioxidants and two ROS‐synthesising oxidases) was quantified using quantitative polymerase chain reaction. This was also performed on keratoconic stromal cells treated in vitro with riboflavin (n = 3).ResultsIn stromal cells from untreated keratoconic corneas (compared with untreated normal corneas), there was an up‐regulation of 7/12 extracellular matrix elements. Four of eight antioxidants and two of two oxidases were also increased. In treated keratoconic corneas (compared with untreated keratoconic corneas), six out of eight normal extracellular matrix constituents were up‐regulated and two of four repair‐type molecules were reduced. An increase was also observed in seven out of eight antioxidants and there was a diminution in two out of two oxidases.ConclusionRiboflavin encourages the synthesis of a normal extracellular matrix and reduces reactive oxygen species levels in keratoconus. This supports the occurrence of wound healing and ROS‐associated abnormalities in keratoconus. By targeting the causative disease mechanisms, riboflavin may have therapeutic potential in the clinical management of keratoconus.

Biomechanical characterization of keratoconus corneas ex vivo with Brillouin microscopy.

Loss of corneal strength is a central feature of keratoconus progression. However, it is currently difficult to measure corneal mechanical changes noninvasively. The objective of this study is to evaluate if Brillouin optical microscopy can differentiate the mechanical properties of keratoconic corneas versus healthy corneas ex vivo. We obtained eight tissue samples from healthy donor corneas used in Descemet's stripping endothelial keratoplasty (DSEK) and 10 advanced keratoconic corneas from patients undergoing deep anterior lamellar keratoplasty (DALK). Within 2 hours after surgery, a confocal Brillouin microscope using a monochromatic laser at 532 nm was used to map the Brillouin frequency shifts of the corneas. The mean Brillouin shift in the anterior 200 μm of the keratoconic corneas at the cone was measured to be 7.99 ± 0.10 GHz, significantly lower than 8.17 ± 0.06 GHz of the healthy corneas (P < 0.001). The Brillouin shift in the keratoconic corneas decreased with depth from the anterior toward posterior regions with a steeper slope than in the healthy corneas (P < 0.001). Within keratoconic corneas, the Brillouin shift in regions away from the apex of the cone was significantly higher than within the cone region (P < 0.001). Brillouin measurements revealed notable differences between healthy and keratoconic corneas. Importantly, Brillouin imaging showed that the mechanical loss is primarily concentrated within the area of the keratoconic cone. Outside the cone, the Brillouin shift was comparable with that of healthy corneas. The results demonstrate the potential of Brillouin microscopy for diagnosis and treatment monitoring of keratoconus.

Repeatability and reproducibility of Galilei measurements in normal keratoconic and postrefractive corneas.

To assess the repeatability and reproducibility of the anterior segment measurements performed with a dual Scheimpflug analyzer (Galilei) in normal, keratoconic and post-refractive surgery corneas. To evaluate the repeatability, two additional measurements were performed by the first examiner. To assess reproducibility, this was later followed by a single reading by the second examiner. The following parameters were recorded and evaluated in this study; central corneal thickness (CCT), thinnest corneal thickness (TCT), mean total corneal power (TCP) in central (0-4mm), mean posterior corneal power (PCP) in central (0.5-2mm), anterior and posterior elevation (best fit sphere [BFS]) in central 8mm anterior and posterior eccentricity (ɛ(2)) in central 8mm. Repeatability and reproducibility for each corneal parameter was assessed using the Bland-Altman analysis. Each of the three groups was consisted of 20 subjects (totally 60 patients, 30 men and 30 women). The 95% LoA for repeatability was very small, indicating small discrepancies between measurements related to CCT. Acceptable repeatability was also achieved for the other parameters in each group. However, the 95% LoA for value TCP was larger in keratoconic eyes. The 95% LoA for reproducibility was also very small, and acceptable for all measured parameters in each group. In addition, the 95% LoA was larger for the measurement of CCT and TCT for postrefractive corneas. The anterior segment measurements provided by Galilei showed good repeatability and reproducibility for normal, keratoconic and postrefractive corneas.

Dynamic Scheimpflug-based assessment of keratoconus and the effects of corneal cross-linking.

To evaluate the ability of the Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) to distinguish between normal and keratoconic corneas and detect the possible stiffening effect of corneal cross-linking (CXL) in vivo. A retrospective study including 86 eyes of 86 participants (27 patients with untreated keratoconus, 27 patients with CXL-treated keratoconus, and 32 normal patients). The prospective study included 9 keratoconic eyes measured 24 days before and 97 days after CXL. The following parameters from the Corvis ST showed a significant difference between keratoconic and normal eyes: intraocular pressure, corneal thickness, first applanation time, highest concavity (HC) radius, HC deformation amplitude, and HC deflection amplitude (analysis of variance, P < .0001). Receiver operating characteristic curve analysis showed the highest area under the curve for HC deflection amplitude (0.942, P < .0001). Prediction intervals for individual measurements within the two groups overlapped considerably. No significant difference was found between the untreated and CXL-treated keratoconus groups (analysis of variance, P > .05). Measurements performed before and after CXL in the same patients showed significant difference in HC deformation amplitude (P = .018), HC time (P = .018), and second applanation time (P = .027). Although the corneal deformation characteristics differed between groups of keratoconic and normal eyes, this study showed that the standard parameters of the Corvis ST cannot readily be used for diagnosis of keratoconus in the individual patient or to document the effect of CXL in vivo.

Corneal endothelial assessment with special references to keratoconus.

This review examines problems associated with in vivo assessment of corneal endothelium with special reference to keratoconus (KC) corneas. The main difficulty appears to be that a single assessment of less than 1/400 of the total number of endothelial cells in any eye may not detect any abnormal levels of heterogeneity. A diagnosis of polymegethism, pleomorphism, corneal guttae, or incipient Fuchs dystrophy may be missed if the sample observed is not representative. Evaluation of the endothelium may be more important in KC when the endothelium may be more susceptible to ultraviolet radiation due to stromal thinning and/or be more susceptible to damage from wearing thicker contact lenses that place hypoxic demands on endothelial deturgescing function. Also, assessment appears to be a greater problem for KC corneas for which central observations are likely to miss any changes in the region of an eccentric cone or in noncentral areas that may be affected by ruptures of the posterior limiting lamina. Apart from genetic influences and ethnic and/or racial considerations, factors such as exposure to ultraviolet and other geographic or vocational variables, atopy, or specific ocular allergies, which may be related to chronic habits of abnormal rubbing and any associated damage due to elevated intraocular pressure, may all contribute to variable presentations of the endothelium. Because of the phenotypic diversity of KC, the status of the endothelium may vary according to many other criteria including age of onset, rate of progression, degree of asymmetry, the type and number of biomicroscopic signs, degree of thinning, and the location, type, and area of the cone, for example. For in vivo assessments, observation of multiple sites is required, but for KC, it should include the cone area to increase the chance of detecting any significant differences from normal.

Biomechanical responses of healthy and keratoconic corneas measured using a noncontact scheimpflug-based tonometer.

To examine the repeatability of measurements obtained using a noncontact Scheimpflug-based tonometer (Corvis ST) and investigate potential differences in these parameters between healthy and keratoconic (KC) corneas. Forty-five keratoconic eyes and 103 healthy eyes were examined using biomicroscopy, corneal tomography and the Corvis ST (CST). Intraocular pressure and central corneal thickness (CCT) were highly repeatable (intraclass correlation [ICC] > 0.70, coefficient of variation [CV] < 0.20). Deformation amplitude (DA) and applanation-1 time (A1T) were fairly repeatable (ICC > 0.60, CV < 0.20). There was no association between DA and age, sex, or ethnicity in healthy eyes. There was a greater mean DA in the KC group compared with 46 age-matched healthy eyes (KC 1.37 ± 0.21 mm, healthy 1.05 ± 0.11 mm, P < 0.001). Multivariate analysis showed DA in KC was predicted by IOP, CCT, and the steepest simulated keratometry value (P = 0.03, P = 0.03, P = 0.001 respectively, R(2) = 0.75). A subgroup analysis of healthy and KC eyes with comparable mean CCT and IOP highlighted a statistically significant difference in mean DA (KC 1.25 ± 0.08 mm, thin healthy 1.13 ± 0.09 mm, P = 0.006). Receiver-operating characteristic analysis showed an area under the curve of 0.77 (95% CI 0.61-0.93, P = 0.006) but no ideal cutoff value for DA. Key parameters assessed by the CST are repeatable. Keratoconus is associated with greater DA than in healthy eyes, even when controlled for CCT and IOP. Deformation amplitude may be a useful adjunct in keratoconus assessment and monitoring, but cannot solely discriminate between healthy and keratoconic corneas.

Deficient repair regulatory response to injury in keratoconic stromal cells

BackgroundKeratoconus manifests as a conical protrusion of the cornea and is characterised by stromal thinning. This causes debilitating visual impairment, which may necessitate corneal transplantation. Hypothetically, many of the pathological features in keratoconus may be manifestations of defects in wound healing; however, as the pathobiology remains unclear, therapeutic targets related to disease mechanisms are currently lacking. This study investigated the protein expression of cytokines which may control stromal wound healing and the effect of an induced secondary injury (SI) on stromal cells from ex vivo human keratoconus and control corneas.MethodsTotal protein was extracted from stromal cells from human keratoconic and non‐keratoconic central corneas (n = 12) with (+SI) and without (‐SI) an ex vivo corneal incision wound. The levels of interleukin 1 alpha (IL‐1α), fibroblast growth factor 2 (FGF‐2), nerve growth factor beta (β‐NGF), insulin‐like growth factor 1 (IGF‐1), tumour necrosis factor alpha (TNF‐α), epidermal growth factor (EGF), transforming growth factor beta 1 (TGF‐β1), platelet‐derived growth factor (PDGF) and hepatocyte growth factor (HGF) were quantified using chemiluminescence‐based immunoarrays.ResultsIn stromal cells from ‐SI keratoconic corneas (compared with ‐SI normal corneas), the levels of IL‐1α, IGF‐1, TNF‐α and TGF‐β1 were increased and the levels of HGF and β‐NGF were reduced. These alterations were also observed in +SI non‐keratoconic corneas (compared with ‐SI non‐keratoconic corneas). In stromal cells from +SI keratoconic corneas (compared with ‐SI keratoconic corneas), the quantities of IL‐1α, FGF‐2, TNF‐a, EGF, TGF‐a1 and PDGF were decreased.ConclusionThe repair‐modulating milieu in keratoconic corneas appears comparable to that in wounded normal corneas. Moreover, wounded keratoconic corneas may be less capable of orchestrating a normal reparative response. These novel findings may improve our understanding of the pathobiology and may facilitate the identification of potential biological targets and therapeutic agents to advance the clinical management of this disorder.

Association of mitochondrial haplogroups H and R with keratoconus in Saudi Arabian patients.

Keratoconic corneas exhibit more mitochondrial DNA (mtDNA) damage than do normal corneas and thus mtDNA may represent a potential candidate for genetic susceptibility studies in keratoconus. To test this hypothesis we determined mitochondrial haplogroups in Saudi patients with keratoconus and healthy controls of same ethnicity. Mitochondrial haplogrouping was performed by polymerase chain reaction-based automated Sanger sequencing in 114 patients with keratoconus and 552 healthy controls. Mitochondrial haplogroups H and R were significantly overrepresented in patients with keratoconus (28.9% vs. 8.5%, P < 0.0001 and 17.5% vs. 3.1%, P < 0.0001, respectively) as compared to healthy controls. Our data suggest that individuals with mitochondrial haplogroups H and R are at increased risk to develop keratoconus. In addition, the results provide further evidence for a plausible role of mtDNA in keratoconus etiology.

Role of biochemical factors in the pathogenesis of keratoconus.

Keratoconus (KC) is a corneal disease associated with structural abnormalities in the corneal epithelium, Bowman's layer and stroma and altered concentration of tear components. KC corneas show a different pattern of collagen lamellae than their normal counterparts. Also, a reduction of several collagen types in KC epithelium and stroma was observed. Altered expression and/or activity of lysyl oxidase, a critical enzyme of the biogenesis of connective tissue detected in KC corneas, may weaken covalent bonds between collagen and elastin fibrils, what may lead to biomechanical deterioration of the cornea. Increased activity of matrix metalloproteinases observed in KC may induce the degradation of the extracellular matrix causing damage to the cornea. Oxidative and nitrative stress play an important role in KC pathogenesis and KC corneas are characterized by the disturbed lipid peroxidation and nitric oxide pathways. Malfunctioning of these pathways may lead to accumulation of their toxic by-products inducing several detrimental effects, along with apoptosis of the corneal cells, which may result from the loss of β-actin or increased levels of cytokines, including interleukin-1 and -6. Change in the expression of genes associated with wound healing, including the nerve growth factor and the visual system homeobox 1, may contribute to increased susceptibility of KC corneas to injury. Consequently, biochemical changes may play an important role in KC pathophysiology and, therefore, can be considered in prevention, diagnosis, prognosis and in the therapy of this disease as well.

Epithelial Remodeling as Basis for Machine-Based Identification of Keratoconus

To develop and evaluate automated computerized algorithms for differentiation of normal and keratoconus corneas based solely on epithelial and stromal thickness data. Maps of the corneal epithelial and stromal thickness were generated from Artemis-1 very high-frequency ultrasound arc-scans of 130 normal and 74 keratoconic subjects diagnosed by combined topography and tomography examination. Keratoconus severity was graded based on anterior curvature, minimum corneal thickness, and refractive error. Computer analysis of maps produced 161 features for one randomly selected eye per subject. Stepwise linear discriminant analysis (LDA) and neural network (NN) analysis were then performed to develop multivariate models based on combinations of selected features to correctly classify cases. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined for each classifier. Stepwise LDA resulted in a six-variable model that provided an AUC of 100%, indicative of complete separation of keratoconic from normal corneas. Leave-one-out analysis resulted in 99.2% specificity and 94.6% sensitivity. Neural network analysis using the same six variables resulted in an AUC of 100% for the training set. Test set performance averaged over 10 trials gave a specificity of 99.5 ± 1.5% and sensitivity of 98.9 ± 1.9%. The LDA function values correlated with keratoconus severity grade. The results demonstrate that epithelial remodeling in keratoconus represents an independent means for differentiation of normal from advanced keratoconus corneas.

Design and Analysis of Keratoconus Tissue Microarrays

The aim was to produce 2 tissue microarrays (TMAs) for keratoconus (KC) corneas and to evaluate the expression of stress-related markers, epidermal growth factor receptor (EGFR), and 8-oxo-2'-deoxyguanosine (8-OHdG), in KC corneas. The corneal buttons of 66 patients with KC were included in both TMAs; 10 Fuchs endothelial corneal dystrophy (FECD), 20 normal autopsy corneas, and 32 nonocular tissue cores served as controls. The expression of immunolabeling for EGFR and 8-OHdG in KC corneas was compared with those of the controls by TMAJ software using an H-score index. To further interpret our findings, pig eyes under different preservation conditions were stained for the same markers. With 2 TMAs, we designed an effective model to investigate KC corneas at the protein level. The EGFR in epithelial cells showed significant upregulation in KC specimens compared with that in FECD controls (P = 0.009), and this was also higher in autopsy controls compared with that in KC corneal samples (P = 0.0002). The 8-OHdG in epithelial cells was elevated in KC samples compared with that in the FECD specimens (P = 0.03), whereas autopsy controls showed higher levels compared with those shown by the KC corneal samples (P < 0.0001). Immunohistochemical staining intensities for both markers in pig corneas correlated with increased time to fixation. TMAs simultaneously enable efficient, high-throughput analysis of tissue samples. The upregulation of EGFR and 8-OHdG protein levels in KC epithelium compared with FECD controls implicates oxidative stress in KC corneas. The expression of these stress markers is increased depending on the time to preservation, which may explain the increased levels of these markers in autopsy control corneas.

Corneal biomechanical assessment using corneal visualization scheimpflug technology in keratoconic and normal eyes.

Purpose. To compare the corneal biomechanical properties of keratoconic patients and age-matched controls using corneal visualization Scheimpflug technology (Corvis ST). Methods. Sixty keratoconic eyes from 47 keratoconus patients and 60 normal eyes from 60 controls were enrolled in this prospective study. Tomography and biomechanical parameters of all eyes were obtained with the Pentacam and Corvis ST, respectively. Intraocular pressure was measured using a Goldmann applanation tonometer. Results. The tomography and biomechanical parameters of the keratoconic corneas were significantly different from those of the normal corneas except for the anterior chamber angle, first applanation length, the highest concavity time, and peak distance. The deformation amplitude was the best predictive parameter (area under the curve: 0.882), with a sensitivity of 81.7%, although there was a significant overlap between keratoconic and normal corneas that ranged from 1.0 to 1.4 mm. In both the keratoconus and control groups, the deformation amplitude was negatively correlated with intraocular pressure, central corneal thickness, and corneal volume at 3 and 5 mm. Conclusions. Corvis ST offers an alternative method for measuring corneal biomechanical properties. The possibility of classifying keratoconus based on deformation amplitude deserves clinical attention.

Modulatory effect of different riboflavin compositions on the central corneal thickness of African keratoconus corneas during collagen crosslinking

Purpose:A pilot investigation to transfer the established corneal collagen crosslinking (CXL) procedure in European eyes into clinically affected African eyes and to optimize the treatment by adapting the riboflavin composition.Materials and Methods:CXL was performed in 15 eyes (11 patients) with advanced stages of keratoconus in the Eye Clinic of Bafoussam in the West Region of Cameroon. The following six riboflavin compositions with different portions of active swelling additives were applied: Solution 1 (0.5% methylhydroxypropylcellulose [MHPC]), solution 2 (1.0% MHPC), solution 3 (1.7% MHPC), solution 4 (5% dextran), solution 5 (10% dextran) and solution 6 (no active swelling ingredient). The central corneal thickness (CCT) was measured by ultrasound pachymetry before and after de-epithelialization and at least every 10 min during CXL.Results:The application of the riboflavin solutions resulted in the following mean final CCT values: 172 ± 15% using solution 1 (60 min/n = 5); 183 ± 8% using solution 2 (60 min/n = 5); 170% using solution 3 (60 min/n = 1); 80% using solution 4 (45 min/n = 1); 99% using solution 5 (45 min/n = 1) and 150 ± 13% using solution 6 (50 min/n = 2).Conclusions:The combination of riboflavin compositions with swelling and stabilizing effects on the corneal stroma seems necessary in African eyes with advanced keratoconus. Further studies are required to confirm these primary results.

Independent Population Validation of the Belin/Ambrósio Enhanced Ectasia Display: Implications for Keratoconus Studies and Screening

ABSTRACT With advances in technology and imaging, finding diagnostic criteria that are both sensitive and specific for keratoconus while using the latest corneal imaging modalities is paramount. The Belin/Ambrósio enhanced ectasia display final ‘D’ index, tested on an independent population, illustrated excellent false positive rates for refractive screening while eliminating 99% of keratoconus corneas. A false positive rate of 0% is achieved with a final ‘D’ of 2.69, meeting the more stringent criteria for treatment studies. How to cite this article Villavicencio OF, Gilani F, Henriquez MA, Izquierdo L Jr, Ambrósio RR Jr, Belin MW. Independent Population Validation of the Belin/Ambrósio Enhanced Ectasia Display:Implications for Keratoconus Studies and Screening. Int J Kerat Ect Cor Dis 2014;3(1):1-8.

Progression of keratoconus in patients wearing pancorneal toric edge rigid gas-permeable contact lenses

To investigate the rate of progression of keratoconus in patients wearing pancorneal toric edge rigid gas-permeable contact lenses (pancorneal RGP-CL) compared to non-pancorneal RGP-CL. We also evaluated alterations in anterior chamber parameters with the progression of keratoconus and investigated the location of the cone in eyes with keratoconus. The current study was a retrospective study including patients with clinically evident keratoconus from the outpatient clinic from the Department of Ophthalmology of the Erasmus Medical Center, Rotterdam, the Netherlands. Medical history and contact lens characteristics were documented. All participants underwent ophthalmic examination including corneal topography. Corneal topography was repeated at one of the consecutive visits of the patient. Patients were divided into two groups: those wearing pancorneal RGP-CL and those wearing other contact lens types. As a measure of progression of keratoconus differences in corneal topography parameters between both groups were compared. A total of 82 patients were included of which 42 had follow-up (mean 17.8 months) data. We found a significant difference in progression between eyes fitted with and without pancorneal RGP-CL (K-flat: p=0.09, K-steep: p=0.02, K-mean: p=0.02, and K-minimum: p=0.04). Compared with eyes fitted without pancorneal RGP-CL no significant difference in K-values was found for eyes fitted with pancorneal RGP-CL during follow-up. Furthermore, a significant decrease in anterior chamber volume (p<0.001) and corneal volume (p=0.008) was found during follow-up. In 86.6% the location of the cone was located infero-temporal. Pancorneal RGP-CL have a better effect on stabilizing progression of keratoconus than non-pancorneal RGP-CL. The finding of an infero-temporal location of the cone in keratoconic corneas may improve results of contact lens fitting and surgical management.

Effects of Corneal Collagen Crosslinking on Corneal Topographic Indices in Patients With Keratoconus

To evaluate the effects of corneal crosslinking (CXL) on corneal topographic indices in patients with progressive keratoconus using Scheimpflug imaging system. This retrospective study comprised 59 eyes of 47 patients who underwent CXL treatment for confirmed progressive keratoconus. Changes in corrected distance visual acuity (CDVA, logMAR equivalent), maximum keratometry (K), and corneal topographic indices included index of surface variance (ISV), index of vertical asymmetry, keratoconus index, center keratoconus index (CKI), index of height asymmetry (IHA), index of height decentration, and minimum radius of curvature (Rmin) were analyzed at 1-year follow-up. Correlations between topographic indices and visual acuity were sought. The study included 59 eyes of 47 patients with progressive keratoconus. The mean CDVA (P<0.001), maximum K (P<0.001), ISV, Rmin, and CKI (P =0.013, P < 0.001, respectively) significantly improved after CXL treatment. Moreover, we found a significant negative correlation between the change in IHA value and the improvement in CDVA (r = -0.351; P = 0.006). In patients with progressive keratoconus, cornea becomes more optically regular after CXL treatment. Changes in topographic indices might be valuable to follow-up the normalization of keratoconic cornea during the postoperative course and superior-inferior height symmetry seems to be associated with visual improvement.

Oxidative Stress in the Pathogenesis of Keratoconus and Fuchs Endothelial Corneal Dystrophy

Due to its localization and function, the cornea is regularly exposed to sunlight and atmospheric oxygen, mainly dioxygen, which produce reactive oxygen species (ROS). Therefore, corneal cells are particularly susceptible to oxidative stress. The accumulation of ROS in the cornea may affect signal transduction, proliferation and may also promote cell death. The cornea has several enzymatic and non-enzymatic antioxidants involved in ROS scavenging, but in certain conditions they may not cope with oxidative stress, leading to diseases of the eye. Keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD) are multifactorial diseases of the cornea, in which pathogenesis is not fully understood. However, increased levels of oxidative stress markers detected in these disorders indicate that oxidative stress may play an important role in their development and progression. These markers are: (i) decreased levels of non-enzymatic antioxidants, and (ii) decreased expression of genes encoding antioxidative enzymes, including thioredoxin reductase, peroxiredoxins, superoxide dismutase, glutathione S-transferase, and aldehyde dehydrogenase. Moreover, the FECD endothelium displays higher levels of oxidative DNA damage, especially in mitochondrial DNA (mtDNA), whereas KC cornea shows abnormal levels of some components of oxidative phosphorylation encoded by mtDNA. In this review we present some considerations and results of experiments supporting the thesis on the important role of oxidative stress in KC and FECD pathology.