Mario Matthaei

Changing Indications in Penetrating Keratoplasty: A Systematic Review of 34 Years of Global Reporting.

Background Penetrating keratoplasty (PK) ranks among the oldest and most common kinds of human tissue transplantation. Based on the hypothesis that reported indications for PK significantly vary between global regions and over time, the present systematic review aimed to provide a thorough overview of global PK indications as reported in peer-reviewed manuscripts. Methods A literature search of PubMed and MEDLINE was conducted to retrieve articles published from January 1980 to May 2014. Indications for PK within 7 global regions were compared using a modified classification system for PK indications and analyzed via multivariate regression. Results A total of 141 publications from 37 countries were included, recording 180 865 PK cases. Postcataract surgery edema was the predominant indication in North America (28.0%) and ranked second in Europe (20.6%), Australia (21.1%), the Middle East (13.6%), Asia (15.5%), and South America (18.6%). Keratoconus was the leading indication in Europe (24.2%), Australia (33.2%), the Middle East (32.8%), Africa (32.4%), and South America (22.8%). It ranked third in North America (14.2%). Keratitis was the primary indication in Asia (32.3%). Fuchs endothelial corneal dystrophy was the fourth most common indication in North America (12.9%) and Europe (10.2%) and fifth in South America (3.8%). Multivariate analysis supported these results and revealed individual regional changes over time. Conclusions Systematic analysis reveals characteristic chronological and regional differences in reported global PK indications. Leading reported indications for PK between 1980 and 2014 were keratoconus (Europe, Australia, the Middle East, Africa, and South America), pseudophakic bullous keratopathy/aphakic bullous keratopathy (North America), and keratitis (Asia).

High-Dose Subconjunctival Cyclosporine A Implants Do Not Affect Corneal Neovascularization after High-Risk Keratoplasty

PURPOSE To test whether subconjunctival cyclosporine A (CsA) implants affect the incidence and the degree of corneal neovascularization occurring after penetrating keratoplasty. DESIGN Prospective, randomized, multicenter, controlled phase 2/3 clinical trial. The study comprised 43 trial sites in Germany, India, and the United States. PARTICIPANTS Enrolled patients (n = 97) were randomized to 1 of 3 groups: treatment group A (n = 36), treatment group B (n = 40), and the control group (n = 21). METHODS Patients from each group received either of 2 doses of subconjunctival CsA (group A, low-dose CsA; group B, high-dose CsA) or placebo (carrier only) implants at the time of high-risk penetrating keratoplasty. MAIN OUTCOME MEASURES The incidence and degree of corneal neovascularization occurring after penetrating keratoplasty were evaluated in a substudy (LX201-01 study: NCT00447187). A web-based image upload system was developed. Standardized digital slit-lamp pictures were quantitatively and objectively evaluated using CellˆF morphometry software. RESULTS No statistically significant difference in incidence and degree of corneal neovascularization developing after penetrating keratoplasty was found between treatment groups and placebo group. Mean corneal neovascularization area at week 52 (visit 12) was 2.32±1.79% in treatment group A versus placebo (2.79±2.11%; P = 0.45) and 2.74±2.22% in treatment group B versus placebo (2.79±2.11%; P = 0.94). CONCLUSIONS High-dose subconjunctival CsA implants do not significantly affect corneal neovascularization after high-risk penetrating keratoplasty. This suggests that local CsA has negligible antiangiogenic effects in the human cornea, at least in the transplant setting.

Anterior segment optical coherence tomography for the diagnosis of corneal dystrophies according to the IC3D classification

Corneal dystrophies are categorized according to the International Committee for Classification of Corneal Dystrophies (IC3D) classification, and their treatment depends on the affected structures and layer of the cornea. Therefore, estimating the depth and extent of the morphological changes due to the specific dystrophy is crucial when deciding between different treatment options. Besides superficial laser treatments and penetrating keratoplasty, minimal invasive lamellar keratoplasties such as Descemet membrane endothelial keratoplasty, deep anterior lamellar keratoplasty, or Descemet stripping automated keratoplasty have become increasingly popular to exchange the specific opaque layers in dystrophic eyes. To determine the morphological changes of the cornea in the different dystrophies, in addition to slit-lamp examination, anterior segment optical coherence tomography has become an important tool with nearly histological resolution. Nonetheless, only a few case series describe the characteristics of changes seen on anterior segment optical coherence tomography. Therefore, we summarize anterior segment optical coherence tomography signs and correlate with slit-lamp examination, as well as the histopathological findings, of corneal dystrophies according to the IC3D classification.

Detection of Pro- and Antiangiogenic Factors in the Human Sclera

ABSTRACT Purpose: Avascular tissues can be used to identify antilymph- or antihemangiogenic factors. The human sclera—the outer covering layer of the eye, lacks lymphatic vessels and contains only a superficial network of blood vessels and was used here to identify endogenous antiangiogenic factors. Methods: Expression levels of a panel of 96 known pro- and antiangiogenic factors were analyzed in 12 scleral or conjunctival control samples from normal human donors using real-time PCR. In vitro, scleral homogenate was cocultured with blood- and lymphatic endothelial cells (BECs and LECs) and immunohistochemistry was performed of scleral fibroblasts and BECs. Results: Three antiangiogenic factors were significantly upregulated in the human sclera compared to the conjunctiva, including FBLN5 (fibulin 5), SERPINF1 (serpin peptidase inhibitor, clade F, member 1 = pigment epithelium derived factor) and TIMP2 (Tissue inhibitor of metalloproteinases 2). Six proangiogenic factors were significantly downregulated in the sclera, including FLT4 (Fms-related tyrosine kinase 4=VEGF-R3), HGF (hepatocyte growth factor), KIT (CD117 / c-kit), PROX1 (prospero homeobox 1), SEMA3F (semaphorin-3F) and TGFA (transforming growth factor alpha). In vitro, scleral homogenate inhibited the growth of both BECs and LECs. Immunohistochemistry labeling of three major antiangiogenic factors from scleral tissue confirmed TIMP3 and PEDF expression both in scleral fibroblasts and in blood endothelial cells, whereas TIMP2 was not detectable. Conclusion: Balancing anti- and proangiogenic factors actively regulates human scleral avascularity, inhibits endothelial cell growth in vitro, and thus may help maintaining the vascular privilege of the inner eye.

MicroRNAs in FECD: A New Therapeutic Option?

miRNAs are a class of small noncoding RNAs inhibiting gene expression at the posttranscriptional level. Studies in ocular and non-ocular tissues demonstrate their potential to serve as biomarkers or treatment targets. Initial studies examining the role of microRNAs in corneal endothelial disorders describe miRNA abnormalities in Fuchs endothelial corneal dystrophy (FECD) and in a syndrome characterized by endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (EDICT syndrome). Improved understanding of the role of miRNAs in physiological and pathological conditions of the corneal endothelium may provide us with new strategies to treat corneal endothelial diseases.

Intraoperative Optical Coherence Tomography in Lamellar Keratoplasties: Indications and Outcomes

Purpose of ReviewLamellar keratoplasties are evolving techniques to selectively replace diseased or opacified layers of the cornea. In recent years, the popularity of lamellar keratoplasties, especially Descemet membrane endothelial keratoplasty, Descemet stripping-automated endothelial keratoplasty and deep anterior lamellar keratoplasty, increased dramatically, since lamellar surgeries reduce intra- and postoperative complications and achieve faster visual recovery. Nonetheless, the surgical procedures are delicate.Recent FindingsNovel imaging techniques, as intraoperative optical coherence tomography (OCT), may substantially help standardize these procedures to even further reduce intra- and postoperative complications and potentially improve outcome.Summary The present review summarizes the current literature regarding the use of intraoperative OCT during lamellar keratoplasties and its effect on postoperative outcome.