Ectatic Corneal Disease Research Articles

Different mRNA expression patterns in keratoglobus and pellucid marginal degeneration keratocytes

PurposeAlike keratoconus (KC), keratoglobus (KG) and pellucid marginal degeneration (PMD) belong to ectatic corneal diseases. While there are numerous studies on keratoconus pathophysiology, there is no exact knowledge on genetic and pathophysiological background of KG and PMD, so far. It is not yet clarified, whether KG and PMD are independent clinical entities or represent different stages of the same disease. Our purpose was to investigate key parameters concerning collagen synthesis, intracellular LOX expression and inflammation in corneal stromal cells of KG and PMD subjects, in vitro. MethodsNormal human keratocytes of corneas from the LIONS Cornea Bank Saar-Lor-Lux, Trier/Westpfalz and human keratocytes of KG and PMD patients were isolated and cultured as keratocytes. To examine Collagen I and V (Col I, Col V), heat shock protein 47 (Hsp47), Lysyl Oxidase (LOX), nuclear factor kappa B (NF-κB) mRNA and protein expression in all cell types, quantitative PCR and Western blot analysis has been performed. ResultsCol5A1 mRNA expression was significantly lower in KG and PMD keratocytes and LOX mRNA expression was significantly higher in KG-keratocytes, compared to controls. Col1A1, Hsp47 and NF-κB mRNA expression and the analyzed protein expressions did not differ from controls, in KG or PMD. ConclusionsCol5A1 mRNA expression is decreased in KG and PMD and LOX mRNA expression is increased in KG. Therefore, the pathophysiology of KG and PMD differs from KC and these seem to be from KC independent entities. The explanation of the peripheral corneal thinning in KG and PMD must be investigated in further studies.

Comparison of obstructive sleep apnea syndrome and keratoconus patients on elevation maps.

This study aimed to compare the tomographic features of the cornea on elevation maps between obstructive sleep apnea syndrome (OSAS) and keratoconus (KC) patients and to investigate the presence of susceptibility to ectatic corneal diseases in OSAS patients. This is a comparative cross-sectional case-control study. This study included 84 eyes of 42 patients diagnosed with severe OSAS using polysomnography (apnea/hypopnea index > 30), 84 eyes of 56 patients diagnosed with keratoconus, and 84 eyes of 42 healthy subjects as control group and evaluated in three groups. Elevation maps of all the groups were performed using Pentacam, and topometric, pachymetric, and deviation indices were recorded. The study included 252 eyes of 130 participants divided in three groups. Comparing all the tomographic keratometric values, a significant difference was found among the three groups. All keratometric values were found to be higher in the OSAS patients group compared to those in the control group. Also topometric indices and Belin-Ambrosio enhanced ectasia display (BAD) were observed to be higher as in subclinical keratoconus and statistically significant when compared to those in the control group. The study reveals the tomographic corneal characteristics and topometric and pachymetric indices of patients with severe OSAS at the time of diagnosis; these findings statistically significantly differ from the control group. In addition to the known association of floppy eyelid in OSAS patients, the suspicion of keratoconus should be kept in mind.

Acoustic micro-tapping optical coherence elastography (AuT-OCE) to quantify biomechanical changes following corneal collagen crosslinking: Ex vivo study

In degenerative corneal diseases, such as keratoconus, local deterioration in mechanical properties results in corneal deformation and vision loss. Collagen cross-linking (CXL) has been used to delay progression of keratoconus with some success in slowing the disease, both long-term and immediate outcomes remain unpredictable for each patient. There is a clear unmet clinical need to develop a personalized biomechanical model based on quantitative maps of corneal mechanical moduli to quantify both biomechanical properties and predict final corneal shape. In this study, we use a novel non-contact, non-invasive AuT-OCE method to quantify corneal elasticity. Because of the anisotropic corneal property due to its collagen structure, a nearly incompressible transversely isotropic (NITI) model was developed to characterize its elasticity. It has been shown that in-plane tensile and out-of-plane shear properties are defined by different moduli, E and G, respectively. Both E and G experienced significantly different stiffening responses to CXL. The increase in G relative to E suggests that while CXL strengthened the tensile strength of the tissue, the ability of the cornea to resist shearing forces was more dramatically altered. AmT-OCE appears capable of changing diagnostic criteria of ectatic corneal diseases, leading to early diagnosis and more precise surgical planning.

PREVALENCE OF KERATOCONUS IN EGYPTIAN ASTIGMATIC PATIENTS

Background: Keratoconus is a corneal ectatic disease characterized by progressive, non-inflammatory corneal disorder, which is characterized by thinning, protrusion of central or paracentral portion of the cornea resulting in irregular astigmatism, myopia, corneal scarring and reduction in visual acuity. The onset of the keratoconus usually occurs at puberty with the progression until the third to fourth decade of the life in most of the cases. Objective: To estimate the prevalence of keratoconus in Egyptian people who have corneal astigmatism using pentacam as an imaging device. Patients and Methods: A retrospective study was done at Al-Sayed Galal University Hospital in Ophthalmology outpatient clinics. The retrieved data revealed 80 eyes of 40 patients photographed during the period from June 2019 to December 2019 by using Scheimpflug imaging device (pentacam) as screening device for keratoconus. All such cases underwent a complete ophthalmic examination that includes visual acuity measurement, refraction, slit lamp biomicroscopy, retinoscopy, fundus examination and corneal topography (pentacam). Results: Mean age of our study cases was 26.55 ± 8 years, which included 22 (55%) males and 18 (45%) females. Cases with KC have higher keratometric corneal values (k1, k2, kmax) and thinner pachymetric values than normal astigmatic eyes. Conclusion: The higher the astigmatism was the higher risk to have keratoconus. Cases with astigmatism ≥ 1.5D who present to outpatient clinics, should undergo corneal topography screening for early diagnosis of KC even if visual acuity is not affected. Pentacam may provide more accurate information about anterior and posterior corneal anatomy especially in suspected eyes.

Thickening of Ectatic Cornea through Regeneration Using Decellularized Corneal Matrix Injectable Hydrogel: A Strategic Advancement to Mitigate Corneal Ectasia.

Ectatic corneal diseases are a group of eye disorders characterized by progressive thinning and outward bulging of the cornea, resulting in vision impairment. A few attempts have been made to use cornea-derived extracellular matrix hydrogels for corneal tissue engineering; however, no studies have investigated its application in corneal ectasia. In this study, we have first developed an animal surgical model that mimics a few specific phenotypes of ectatic cornea. Later, we investigated the potential of decellularized cornea matrix hydrogels (dCMH) from both human and bovine sources in increasing the thickness of the cornea in the developed surgical model. Our data advocate that surgical stromal depletion can be followed to establish ectatic models and can also provide information on the biocompatibility of materials, its integration with native stroma, degradation over time, and tissue remodeling. We observed that dCMH from both sources could integrate with ectatic thin corneal stroma and helps in regaining the thickness by regenerating a reasonably functional and transparent stroma; however, no significant difference was spotted between the dCMH made from human and bovine corneal tissue sources. Hence, this study is a promising step toward developing a non-invasive technique for the treatment of corneal ectasia by using dCMH.

Arginine Supplementation Promotes Extracellular Matrix and Metabolic Changes in Keratoconus.

Keratoconus (KC) is a common corneal ectatic disease that affects 1:500–1:2000 people worldwide and is associated with a progressive thinning of the corneal stroma that may lead to severe astigmatism and visual deficits. Riboflavin-mediated collagen crosslinking currently remains the only approved treatment to halt progressive corneal thinning associated with KC by improving the biomechanical properties of the stroma. Treatments designed to increase collagen deposition by resident corneal stromal keratocytes remain elusive. In this study, we evaluated the effects of arginine supplementation on steady-state levels of arginine and arginine-related metabolites (e.g., ornithine, proline, hydroxyproline, spermidine, and putrescine) and collagen protein expression by primary human corneal fibroblasts isolated from KC and non-KC (healthy) corneas and cultured in an established 3D in vitro model. We identified lower cytoplasmic arginine and spermidine levels in KC-derived constructs compared to healthy controls, which corresponded with overall higher gene expression of arginase. Arginine supplementation led to a robust increase in cytoplasmic arginine, ornithine, and spermidine levels in controls only and a significant increase in collagen type I secretion in KC-derived constructs. Further studies evaluating safety and efficacy of arginine supplementation are required to elucidate the potential therapeutic applications of modulating collagen deposition in the context of KC.

Potential role of ocular surface microbiota in keratoconus etiopathogenesis

ABSTRACT Introduction Keratoconus is the most common corneal ectatic disease and the most common cause of corneal transplantation in developed countries. The etiopathogenesis of the disease remains unclear. Areas covered The human body hosts a remarkably abundant and diverse community of microbial species called microbiota. Advances in next-generation sequencing (NGS) technology and bioinformatics have facilitated the characterization of human microbiota. Previous studies have shown that there is an alteration of ocular microbiota in inflammatory and autoimmune ocular diseases. The purpose of this review article is to evaluate the potential effect of ocular microbiota on the pathophysiology of keratoconus. Expert opinion Recent studies have shown the low-level chronic inflammatory process in keratoconus. A regulatory interaction has been demonstrated between human microbiota and Toll-like receptors, which are innate immune system receptors. In addition, Toll-like receptor activity in keratoconus has been shown to be higher than in normal individuals. Therefore, the alteration of ocular microbiota may have a potential role in keratoconus etiopathogenesis. Further research is required on this subject.

Outcomes of Conductive Keratoplasty Combined with Corneal Crosslinking in Advanced Ectatic Corneal Disease

PurposeTo assess the effectiveness of a novel treatment for patients with advanced corneal ectasia and loss of visual acuity (VA). Conductive keratoplasty (CK) is performed to improve VA followed by epithelium-on (epi-on) corneal crosslinking (CXL) to stabilize the cornea after CK.MethodsRetrospective, exploratory cohort study. Patients with keratoconus or postsurgical ectasia and best spectacle-corrected distance VA (CDVA) ≤ 20/40 were included. Conductive keratoplasty was performed (ViewPoint CK System, Refractec, Inc., Bloomington, MN); followed a day later by epi-on CXL (CXLUSA/CXLO, Bethesda, MD/CXLO Encinitas, CA). Measures included uncorrected distance visual acuity (UDVA) and CDVA, as well as refractive and tomographic measures and tomographic indices.ResultsData from 50 eyes of 45 patients were analyzed. Mean follow-up was 15.1 ± 12.2 months (range: 2 to 51). Overall, UDVA and CDVA improved postoperatively. Subjective refraction and tomographic metrics did not show consistent changes, but changes in tomographic indices were associated with treatment follow-up time. At the 1-year visit, mean UDVA significantly improved over baseline (P = 0.009) by approximately 3 lines; mean CDVA improved significantly (P = 10−5) by approximately 2 lines. No eye lost lines of CDVA. Change in the Index of Surface Variance (ISV) was associated with treatment, and the D-Index trended over follow-up time.ConclusionConductive keratoplasty with a proprietary epi-on CXL treatment improved vision in patients with advanced ectasia This CK/epi-on CXL treatment offers the possibility of improved VA for patients with compromised vision due to ectasia.

Pediatric keratoconus - Current perspectives and clinical challenges.

Keratoconus is an ectatic corneal disease characterized by progressive stromal thinning, irregular astigmatism, and defective vision. It can be unilateral or bilateral with asymmetric presentation. It starts at puberty and either progresses rapidly to an advanced stage of the disease or stops in case of delayed onset and slow progression. Pediatric keratoconus is more aggressive than in adults and the management protocols differ because of various rationales such as accelerated progression, advanced stage of disease at the time of diagnosis and co-morbidities. It poses a burden to the society as it affects the quality of life, social, and educational development in children. Hence early diagnosis, recognition of progression, and timely intervention with collagen crosslinking is imperative to arrest the worsening. Association with systemic syndromes and ocular comorbidities can be of concern in pediatric keratoconus. Severe ocular allergy when associated hastens progress and complicates timely intervention of crosslinking treatment and compliance to contact lens wear. Keratoplasty in pediatric keratoconus has good outcomes but can encounter frequent suture-related concerns. This article discusses the epidemiology, etiopathogenesis, clinical challenges, and current perspectives of management of pediatric keratoconus.

Ectatic diseases

Ectatic corneal disease (ECD) comprises a group of disorders characterized by progressive thinning and subsequent bulging of the corneal structure. Different phenotypes have been recognized, including keratoglobus, pellucid marginal degeneration (PMD), and keratoconus (KC). Keratoconus has been widely investigated throughout the years, but the advent of laser refractive surgery boosted an immediate need for more knowledge and research about ectatic diseases. This article discusses nomenclature of ectatic disease, etiology and pathogenesis, along with treatment options, with special focus ok KC and forme fruste keratoconus.

Lamellar Keratoplasty for Advanced Keratoconus.

Ectatic corneal diseases are a group of disorders resulting in progressive corneal steepening and thinning. Keratoconus, keratoglobus, pellucid marginal degeneration, post-keratorefractive ectasia, and corneal graft ectasia are the types of corneal ectasia. Early diagnosis with appropriate diagnostic tools can help prevent progression, eliminating the need for corneal transplantation. Lamellar or full thickness corneal transplantation are the treatment options for advanced diseases. Although the visual outcomes of penetrating keratoplasty are comparable to anterior lamellar keratoplasty (ALK) especially in keratoconus, ALK is the preferred treatment of choice considering benefits including reduced graft rejection, less long-term complications, and better graft survival. This article reviews the various surgical techniques in ALK with its clinical outcomes in advanced keratoconus.

Scleral Topography-Guided Scleral Lens Fitting

Keratoconus is a progressive corneal ectatic disease that leads to corneal shape irregularity and subsequent blur, visual distortion, and glare. One of the best non-surgical treatments for those suffering from keratoconus are scleral lenses. The ability of scleral lenses to compensate for irregular astigmatism allows patients to see clearer, more comfortably, and with visual stability. Technological advances such as Map3D scleral topography allow for a more precise first lens, which enhances initial comfort and vision, all while reducing chair time. Despite technological guidance, considerations must still be made to conjunctival settling, corneal edema, and corneal hypoxia. CE Notification: This article is available as a COPE accredited CE course. You may take this course for 1-hour credit. Read the article and take the qualifying test to earn your credit. Click here to Enroll (https://www.crojournal.com/scleral-topography-guided-scleral-lens-fitting) Please check COPE course expiry date prior to enrollment. The COPE course test must be taken before the course expiry date.

Quasi-Static Optical Coherence Elastography to Characterize Human Corneal Biomechanical Properties.

PurposeQuasi-static optical coherence elastography (OCE) is an emerging technology to investigate corneal biomechanical behavior in situations similar to physiological stress conditions. Herein OCE was applied to evaluate previously inaccessible biomechanical characteristics of human corneal tissue and to study the role of Bowman's layer in corneal biomechanics.MethodsHuman corneal donor buttons (n = 23) were obtained and Descemet's membrane and endothelium were removed. In 11 corneas, Bowman's layer was ablated by a 20 µm stromal excimer laser ablation. Buttons were mounted on an artificial anterior chamber and subjected to a pressure modulation from 10 to 30 mm Hg, and back to 10 mm Hg, in steps of 1 mm Hg. At each step, a spectral-domain optical coherence tomography scan was obtained. Displacements were analyzed by optical flow tracking, and strain over the entire stromal depth was retrieved from the phase gradient of the complex interference signal.ResultsDuring pressure increase, corneal tissue moved upward (486–585 nm/mm Hg) but did not fully recover (Δ= 2.63 to 8.64 µm) after pressure decrease. Vertical corneal strain distribution was negative in the anterior and positive in the posterior cornea, indicating simultaneous corneal compression and expansion, respectively. Bowman's layer caused minor localized differences in corneal strain distribution.ConclusionsCorneal strain distribution is more complex than previously assumed, with a fundamental difference in mechanical response between the anterior and posterior stroma. Clinically, OCE technology might be used to monitor the progression of corneal ectatic diseases and to determine the success of corneal cross-linking.

Keratoconus and Ectatic Disease: Evolving Criteria for Diagnosis.

The approach to corneal ectatic disease has changed dramatically over the last decade with advances in both diagnosis and treatment. Newer treatments, such as corneal cross-linking, have the potential to slow or stop the progression of the disease, but benefit from earlier identification of the disease than had previously been possible or required. The continued use of older diagnostic criteria and ambiguous terminology can lead to erroneous study conclusions that may not be applicable to patients with true pathology.

Optimizing outcomes for keratoplasty in ectatic corneal disease.

Advanced keratectasia often requires corneal transplantation for restoration of vision. This review discusses the surgical approach suitable for these cases including significant updates in the current literature. With greater understanding of ectatic corneal disease and its associated operative challenges, several modifications in the surgical approach have been developed. Identified predictive factors for successful pneumatic dissection and intraoperative complications have informed surgical planning and decision-making. In the setting of failed pneumatic dissection, sequential use of alternative lamellar dissection techniques is a reasonable surgical strategy. Surgical refinements to optimize visual outcomes and postoperative interventions to correct residual refractive errors have improved visual rehabilitation after keratoplasty. With evidence of its undisputed advantages, DALK has been widely recognized as the primary surgical option for ectatic corneal disease.

The Role of Corneal Biomechanics for the Evaluation of Ectasia Patients.

Purpose: To review the role of corneal biomechanics for the clinical evaluation of patients with ectatic corneal diseases. Methods: A total of 1295 eyes were included for analysis in this study. The normal healthy group (group N) included one eye randomly selected from 736 patients with healthy corneas, the keratoconus group (group KC) included one eye randomly selected from 321 patients with keratoconus. The 113 nonoperated ectatic eyes from 125 patients with very asymmetric ectasia (group VAE-E), whose fellow eyes presented relatively normal topography (group VAE-NT), were also included. The parameters from corneal tomography and biomechanics were obtained using the Pentacam HR and Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany). The accuracies of the tested variables for distinguishing all cases (KC, VAE-E, and VAE-NT), for detecting clinical ectasia (KC + VAE-E) and for identifying abnormalities among the VAE-NT, were investigated. A comparison was performed considering the areas under the receiver operating characteristic curve (AUC; DeLong’s method). Results: Considering all cases (KC, VAE-E, and VAE-NT), the AUC of the tomographic-biomechanical parameter (TBI) was 0.992, which was statistically higher than all individual parameters (DeLong’s; p < 0.05): PRFI- Pentacam Random Forest Index (0.982), BAD-D- Belin -Ambrosio D value (0.959), CBI -corneal biomechanical index (0.91), and IS Abs- Inferior-superior value (0.91). The AUC of the TBI for detecting clinical ectasia (KC + VAE-E) was 0.999, and this was again statistically higher than all parameters (DeLong’s; p < 0.05): PRFI (0.996), BAD-D (0.995), CBI (0.949), and IS Abs (0.977). Considering the VAE-NT group, the AUC of the TBI was 0.966, which was also statistically higher than all parameters (DeLong’s; p < 0.05): PRFI (0.934), BAD- D (0.834), CBI (0.774), and IS Abs (0.677). Conclusions: Corneal biomechanical data enhances the evaluation of patients with corneal ectasia and meaningfully adds to the multimodal diagnostic armamentarium. The integration of biomechanical data and corneal tomography with artificial intelligence data augments the sensitivity and specificity for screening and enhancing early diagnosis. Besides, corneal biomechanics may be relevant for determining the prognosis and staging the disease.

Noninvasive detection of nanoscale structural changes in cornea associated with cross-linking treatment.

Corneal cross-linking (CXL) using ultraviolet-A (UVA) irradiation with a riboflavin photosensitizer has grown from an interesting concept to a practical clinical treatment for corneal ectatic diseases globally, such as keratoconus. To characterize the corneal structural changes, existing methods such as X-ray microscopy, transmission electron microscopy, histology and optical coherence tomography (OCT) have been used. However, these methods have various drawbacks such as invasive detection, the impossibility for in vivo measurement, or limited resolution and sensitivity to structural alterations. Here, we report the application of oversampling nanosensitive OCT for probing the corneal structural alterations. The results indicate that the spatial period increases slightly after 30 minutes riboflavin instillation but decreases significantly after 30 minutes UVA irradiation following the Dresden protocol. The proposed noninvasive method can be implemented using existing OCT systems, without any additional components, for detecting nanoscale changes with the potential to assist diagnostic assessment during CXL treatment, and possibly to be a real-time monitoring tool in clinics.

Changes in corneal biomechanics during pregnancy in Chinese healthy female

To evaluate the changes of corneal biomechanics and the intraocular pressure during pregnancy in a Chinese healthy female population. A total of 222 unrelated Chinese females were recruited: 52 non-pregnant, 15 pregnant in the first trimester, 68 pregnant in the second trimester, and 87 pregnant in the third trimester. The intraocular pressure and corneal biomechanical parameters, including corneal-compensated intraocular pressure, Goldmann-correlated intraocular pressure, corneal hysteresis, and corneal resistance factor, were measured by an Ocular Response Analyzer G3. Central corneal thickness was measured by Lenstar (LS900). Corneal hysteresis and corneal resistance factor were significantly higher in pregnant women at the second and third trimesters. Corneal-compensated intraocular pressure was lower in women at the third trimester of pregnancy (p = 0.023), but the difference became insignificant after adjustment for corneal hysteresis. Central corneal thickness was marginally higher in pregnant women than non-pregnant women (p = 0.032). There was a negative correlation between corneal-compensated intraocular pressure and corneal hysteresis (r = -0.337, p < 0.001) and a positive correlation between central corneal thickness and corneal hysteresis (r = 0.711, p < 0.0001). After adjustment for corneal-compensated intraocular pressure, corneal hysteresis remained significantly higher in the second and third trimesters of pregnant women than non-pregnant women (p = 0.031, p = 0.005). This study revealed a significant increase in corneal hysteresis and corneal resistance factor in the second and third trimesters. The increase of corneal hysteresis was independent of corneal-compensated intraocular pressure, indicating pregnant females have unique characteristics in corneal-compensated intraocular pressure and corneal biomechanical properties that may be related to glaucoma and corneal ectatic diseases in pregnancy.

ABCD: A new classification for keratoconus.

Recent advances in the diagnosis and treatment of ectatic corneal disease have mandated a more modern staging system. The new Belin ABCD keratoconus staging system incorporates anterior and posterior curvature centered on the thinnest point of the cornea, thinnest pachymetry values and distance visual acuity in grades from 0-4. By including posterior curvature and thickness measurements based on the thinnest point, as opposed to apical, the new staging system better reflects anatomical changes seen in keratoconus and other ectatic diseases.

Updates on management of pellucid marginal degeneration: Topographic patterns, differential diagnosis, and surgical options

Pellucid marginal degeneration (PMD) is a rare ectatic corneal disease involving the inferior part of the cornea. It is difficult to differentiate between keratoconus (KCN) and PMD by slit lamp, especially in the detection of early and subclinical stages of the diseases. Corneal topography is the main diagnostic tool of PMD with characteristic diagnostic patterns “crab-claw” or “butterfly.” PMD could be mistaken as KCN, keratoglobus, and other peripheral thinning conditions such as Terrien marginal degeneration and Mooren's ulcer. Spectacles, soft and rigid gas permeable contact lens are the main visual correcting method in early stage of the disease. Different surgical techniques are available for PMD management; however, none of them were found to be effective, so further studies will be needed in the future.