Combined biomechanical and tomographic keratoconus staging: Adding a biomechanical parameter to the ABCD keratoconus staging system.

PURPOSE: This retrospective cross-sectional study evaluated the potential of an additional biomechanical parameter 'E' as an addition to the tomographic ABCD ectasia/keratoconus (KC) staging. METHODS: The Corvis Biomechanical Factor (CBiF) represents the modified linear term of the Corvis Biomechanical Index (CBI) developed based on 448 KC corneas from the Homburg Keratoconus Center (HKC). The CBiF range was divided into five stages (E0 to E4) to create a grading system according to the ABCD stages. Stage E0 was characterized by values smaller than the 2.5 percentile. The thresholds were created by dividing the CBiF range between the 2.5 and 97.5 percentiles into four groups of equal values (E1-E4). The frequency distribution of 'E' was analysed and independently validated based on another 860 KC corneas dataset from Milano and Rio de Janeiro (MR). The relationship between 'E' and the ABCD staging was analysed by cross-tabulation. The specificity of 'E' was assessed based on healthy controls (112|851) from both datasets (HKC|MR). RESULTS: 'E' was normally distributed with E0 = 37|30, E1 = 86|200, E2 = 155|354, E3 = 101|206, E4 = 69|70 in the KC group and 96.4%|90.5% of the controls classified E0 in the HKC|MR dataset, respectively. Cross-tabulation revealed that 'E' was most comparable to posterior corneal curvature ('B') in both datasets, while showing a trend towards more advanced stages in comparison to anterior corneal curvature ('A') and thinnest corneal thickness ('C'). CONCLUSION: The novel Corvis-derived parameter 'E' provides a biomechanical staging for ectasia/KC potentially enhancing the ABCD staging and may detect abnormalities before tomographic changes, which requires further studies.

Correlation of the Corvis Biomechanical Factor with tomographic parameters in keratoconus.

PURPOSE: To investigate the relationship between corneal biomechanics and keratoconus (KC) severity as described by tomographic parameters. SETTING: University-based German ophthalmology department. DESIGN: Retrospective cross-sectional study. METHODS: A total of 448 KC corneas of the Homburg Keratoconus Center and 112 healthy corneas (448+112 patients) were examined by Pentacam high-resolution and Corneal Visualization Scheimpflug Technology (Pentacam HR and Corvis ST). The KC population included a wide spectrum of disease severity based on Belin's ABCD classification. Linear regression analysis was performed between the linear term of the Corvis Biomechanical Index (CBI) (CBI beta) and the tomographic values anterior radius of curvature (ARC), posterior radius of curvature (PRC), and thinnest corneal thickness (TCT). A linear transformation of the CBI beta was performed to provide an intuitive scaling, which was referred to as the Corvis Biomechanical Factor (CBiF = -0.24294226 × CBI beta + 6.02). This scaling adjusted the CBI beta to the same scale as posterior corneal curvature (PRC). RESULTS: There was a high correlation of the CBI beta and its modification, the CBiF, with TCT (Pearson, r = -0.775), ARC (r = -0.835), and PRC (r = -0.839) in the KC population (P < .001). In the control corneas, the correlation between the CBI beta and ARC was weak (r = -0.216, P = .022), not significant (PRC, r = -0.146, P = .125), or moderate (TCT, r = -0.628, P < .001). CONCLUSIONS: The linear term of the CBI was highly associated with KC severity as defined by corneal tomography. The CBiF represents a new scale based on biomechanical characteristics in KC, which could serve as a basis for a biomechanical KC classification in the future.

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.

Evolution of Keratoconus: From Diagnosis to Therapeutics.

This review describes the evolution of the diagnosis and treatment of keratoconus from the earliest written description to present day. The first description was provided in 1736 by Benedict Duddell who described the prominent corneas of a fourteen-year-old boy. Throughout the 19th century, a variety of surgical procedures were proposed to manage the disease, such as surgically repositioning the pupil away from the cone, iris incarceration to produce a slit-like pupil, cauterization of the cone to produce a scar, and full thickness elliptical excision of the cone. Despite the ingenuity of these procedures, many led to serious complications. In 1936, Ramon Castroviejo revolutionized surgical management by performing the first corneal transplant for keratoconus. The advent of refractive surgery in the 1990s brought about a sudden and critical need for better understanding of keratoconus and corneal ectatic disease. Topographic analysis allowed for earlier detection of keratoconus, prior to clinical signs and symptoms. Tomographic analysis provided analysis of the anterior and posterior surfaces of the cornea and allowed for even earlier detection. The Belin/Ambrosio Enhanced Ectasia Display on the Pentacam incorporates anterior and posterior elevation, pachymetric map, best fit sphere and enhanced reference surface to provide an overall "D" value that is predictive of ectatic disease. This display allows refractive providers to quickly and accurately screen potential refractive surgery candidates to identify those at risk for ectasia and early subclinical keratoconus. Corneal crosslinking was revolutionary in the treatment of keratoconus. There have been several randomized controlled trials that have found it to be safe and effective to halt ectatic progression. Crosslinking was recently approved by the FDA for progressive keratoconus. Currently, there is no clear definition of ectasia progression. Providers must be able to clearly, objectively and consistently diagnose progressive disease to institute timely treatment in the population with the greatest potential benefit. The new Belin ABCD grading system and progression analysis incorporated into the Oculus Pentacam software provides an objective way of assessing progression over time. Keratoconus diagnosis and management have grown tremendously since the first description in 1736, but there is still much to learn about keratoconus and its management.

High MMP-9 Expression May Contribute to Retroprosthetic Membrane Formation after KPro Implantation in Rabbit Corneal Alkali Burn Model.

Purpose. To evaluate aqueous humor MMP-9 levels in alkali-burned rabbit cornea following KPr implantation and their roles in RPMs formation. Methods. Left eyes of 36 rabbits received a deep corneal alkali wound. 12 corneas were implanted with KPro and the other 24 control corneas were either penetrating keratoplasty or left without keratoplasty. Aqueous humor MMP-9 and TIMP-1 levels were determined and RPMs were obtained for histopathological and ultrastructural examination. Results. Alkali exposure induced significant increase in aqueous humor MMP-9 level and the data were further enhanced by KPro implantation. By contrast, TMIP-1 levels in aqueous humor showed a decreased trend following corneal alkali burn and KPro surgery. RPMs were developed in 5 out of 10 cases of KPro successfully implanted eyes. Histopathology showed the presence of a large number of fibroblasts and collagen fibers arranged irregularly with inflammatory cells infiltration, and an ingrowth of new blood vessels in this retrokeratoprosthesis fibrous tissue. Immunohistochemical analysis showed positive stain of RPMs for both MMP-9 and TIMP-1. Aqueous humor MMP-9 levels were significantly higher in RPM group postoperatively, while TIMP-1 levels were comparatively lower than that of No-RPM group. Conclusions. Our study evidenced the potential pathophysiological role of MMP-9 expression in RPM formation following KPro implantation.

Experimental study on cryotherapy for fungal corneal ulcer.

BACKGROUND: Fungal corneal ulcer is one of the major causes of visual impairment worldwide. Treatment of fungal corneal ulcer mainly depends on anti-fungal agents. In the current study, we developed an integrated combination therapy of cryotherapy and anti-fungal agents to facilitate effective treatment of fungal corneal ulcer. METHODS: Rabbit models of cornea infection were established using a combined method of intrastromal injection and keratoplasty. After treatment with cryotherapy and anti-fungal agents, scanning electron microscopy, transmission electron microscopy, and confocal microscopy were conducted to observe changes in microstructure in the rabbits. Periodic acid Schiff A and hematoxylin and eosin staining were used for detection of histological changes. RESULTS: Continuous scanning electron microscopy and transmission electron microscopy observations showed that cryothermal treatment inhibited growth of fungal mycelium by destroying fungal cellular structures. Typical cryotherapy was effective in curing fungal corneal ulcer. Different fungi showed different susceptibilities to treatment. The curative effect of Candida albicans was the best, while that of Aspergillus fumigates was the worst. CONCLUSIONS: Our study provides a novel method of a combination of cryotherapy and anti-fungal agents for treatment of fungal corneal ulcer. This treatment could help facilitate the practice of fungal keratitis treatment in the future.

Efficacy and Safety of Corneal Transplantation Using Corneas from Foreign Donors versus Domestic Donors: A Prospective, Randomized, Controlled Trial.

Purpose. To assess the efficacy and safety of corneal transplantation using corneas from foreign donors. Methods. One hundred and eight patients needing therapeutic penetrating keratoplasty were randomly divided into 2 groups (54 cases/group): foreign group using foreign donor corneas and domestic group using domestic donor corneas. Clinical outcome and incidence of postoperative complications were compared between groups. Results. No significant difference with respect to the therapeutic outcome and postoperative Best Corrected Visual Acuity (BCVA) and neovascularization by final follow-up was observed between the two groups. The graft thickness in the foreign group was statistically higher than the domestic group at 1 month postoperatively, but not at 3, 6, and 12 months postoperatively. Corneal endothelial cell density in the domestic group was statistically higher than in the foreign group at 3, 6, and 12 months postoperatively. Corneal epithelial abnormalities in the foreign group were significantly higher than that in domestic group. The primary graft failure, incidence of graft survival, and postoperative complications such as immunologic rejection, graft infection, and secondary glaucoma were not significantly different between the two groups. Conclusions. Corneal transplantations using foreign donor corneas are as effective and safe as those using domestic donor corneas.