IntroductionKeratoconus (KC) is a complex, genetically heterogeneous, multifactorial degenerative disorder that is accompanied by corneal ectasia which usually progresses asymmetrically. With an incidence of approximately 1 per 2000 and 2 cases per 100,000 population presenting annually, KC follows an autosomal recessive or dominant pattern of inheritance and is, apparently, associated with genes that interact with environmental, genetic, and/or other factors. This is an important consideration in refractive surgery in the case of familial KC, given the association of KC with other genetic disorders and the imbalance between dizygotic twins. The present review attempts to identify the genetic loci contributing to the different KC clinical presentations and relate them to the common genetically determined comorbidities associated with KC.MethodsThe PubMed, MEDLINE, Google Scholar, and GeneCards databases were screened for KC-related articles published in English between January 2006 and November 2017. Keyword combinations of “keratoconus,” “risk factor(s),” “genetics,” “genes,” “genetic association(s),” and “cornea” were used. In total, 217 articles were retrieved and analyzed, with greater weight placed on the more recent literature. Further bibliographic research based on the 217 articles revealed another 124 relevant articles that were included in this review. Using the reviewed literature, an attempt was made to correlate genes and genetic risk factors with KC characteristics and genetically related comorbidities associated with KC based on genome-wide association studies, family-based linkage analysis, and candidate-gene approaches.ResultsAn association matrix between known KC-related genes and KC symptoms and/or clinical signs together with an association matrix between identified KC genes and genetically related KC comorbidities/syndromes were constructed.ConclusionTwenty-four genes were identified as potential contributors to KC and 49 KC-related comorbidities/syndromes were found. More than 85% of the known KC-related genes are involved in glaucoma, Down syndrome, connective tissue disorders, endothelial dystrophy, posterior polymorphous corneal dystrophy, and cataract.

IntroductionKeratoconus (KC) is a complex, genetically heterogeneous multifactorial degenerative disorder characterized by corneal ectasia and thinning. Its incidence is approximately 1/2000–1/50,000 in the general population. KC is associated with moderate to high myopia and irregular astigmatism, resulting in severe visual impairment. KC structural abnormalities primarily relate to the weakening of the corneal collagen. Their understanding is crucial and could contribute to effective management of the disease, such as with the aid of corneal cross-linking (CXL). The present article critically reviews the proteins involved in the pathophysiology of KC, with particular emphasis on the characteristics of collagen that pertain to CXL.MethodsPubMed, MEDLINE, Google Scholar and GeneCards databases were screened for relevant articles published in English between January 2006 and June 2018. Keyword combinations of the words “keratoconus,” “risk factor(s),” “genetics,” “genes,” “genetic association(s),” “proteins”, “collagen” and “cornea’’ were used. In total, 272 articles were retrieved, reviewed and selected, with greater weight placed on more recently published evidence. Based on the reviewed literature, an attempt was made to tabulate the up- and down-regulation of genes involved in KC and their protein products and to delineate the mechanisms involved in CXL.ResultsA total of 117 proteins and protein classes have been implicated in the pathogenesis and pathophysiology of KC. These have been tabulated in seven distinct tables according to their gene coding, their biochemistry and their metabolic control.ConclusionThe pathogenesis and pathophysiology of KC remain enigmatic. Emerging evidence has improved our understanding of the molecular characteristics of KC and could further improve the success rate of CXL therapies.

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Background and Purpose: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in immunocompromised children. The purpose of our study was to evaluate the incidence of IFIs in pediatric patients with underlying hematologic malignancies and determine the patient characteristics, predisposing factors, diagnosis, treatment efficacy, and outcome of IFIs. Materials and Methods: For the purpose of the study, a retrospective analysis was performed on cases with proven and probable fungal infections from January 2001 to December 2016 (16 years). Results: During this period, 297 children with hematologic malignancies were admitted to the 2nd Pediatric Department of Aristotle University of Thessaloniki, Greece, and 24 cases of IFIs were registered. The most common underlying diseases were acute lymphoblastic leukemia (ALL; n=19, 79%), followed by acute myeloid leukemia (AML; n=4, 17%) and non-Hodgkin lymphoma (NHL; n=1, 4%). The crude incidence rates of IFIs in ALL, AML, and NHL were 10.5%, 18.2%, and 2.8% respectively. Based on the results, 25% (n=6) and 75% (n=18) of the patients were diagnosed as proven and probable IFI cases, respectively. The lung was the most common site of involvement in 16 (66.7%) cases. Furthermore, Aspergillus and Candida species represented 58.3% and 29.1% of the identified species, respectively. Regarding antifungal treatment, liposomal amphotericin B was the most commonly prescribed therapeutic agent (n=21), followed by voriconazole (n=9), caspofungin (n=3), posaconazole (n=3), micafungin (n=1), and fluconazole (n=1). In addition, 12 children received combined antifungal treatment. The crude mortality rate was obtained as 33.3%.  Conclusion: As the findings of the present study indicated, despite the progress in the diagnosis and treatment of IFIs with the use of new antifungal agents, the mortality rate of these infections still remains high.