Radiation treatment methods in uveal melanoma.

Background: The most frequent primary ocular malignancy in the western world is the uveal melanoma. While it mainly affects Caucasians, it is extremely uncommon among non-Caucasians. Continuous improvement in therapies for local treatment has allowed sparing of the eye, although this approach apparently does not improve survival. The present review aimed to explain different radiotherapy (RT) methods and compare the pros and cons of each method, along with the main complications that may be encountered in the treatment of uveal melanoma. Methods: Relevant papers published between September 2009 and January 2021 were retrieved, reviewed, and screened. Four databases, including PubMed, MEDLINE, Google Scholar, and GeneCards, were searched for this purpose. Results: Forty-one relevant articles were identified. Based on the selected papers, we highlighted the advantages and disadvantages of the different RT methods that have allowed sparing of the eye, even though they have not, as yet, improved survival. We listed a detailed comparison between therapies that allow an educated choice among the different available RT methods. Conclusions: The choice of uveal melanoma management is determined by the location of the tumor and volume of the extraocular extent. At present, there is no gold standard for the management of all ocular melanomas, and each case should be approached individually. Therefore, classification is a valuable prognostic tool. Many cases in cT3-4 classification categories are treated by primary enucleation and conservative treatment follow-up, while in cT2 and most cT1 classifications (i.e., 3.1-6.0-mm tumor thickness), several forms of RT are used.

A Review of Last Decade Developments on Epiretinal Membrane Pathogenesis.

Epiretinal membrane (ERM) is a pathologic tissue that develops at the vitreoretinal interface. ERM is responsible for pathological changes of vision with varying degrees of clinical significance. It is either idiopathic or secondary to a wide variety of diseases such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). A great variation in the prevalence of idiopathic ERM among different ethnic groups proposed that genetic and lifestyle factors may play a role in ERM occurrence. Histopathological studies demonstrate that various cell types including retinal pigment epithelium (RPE) cells, fibrocytes, fibrous astrocytes, myofibroblast-like cells, glial cells, endothelial cells (ECs) and macrophages, as well as trophic and transcription factors, including transforming growth factor (TGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) etc., are directly or indirectly involved in the pathogenesis of idiopathic or secondary ERMs. These processes are driven (on the last count) by more than 50 genes, such as Tumor Necrosis Factor (TNF), CCL2 (chemokine (C-C motif) ligand )), Metastasis Associated Lung Adenocarcinoma Transcript 1 )MALAT1(, transforming growth factor (TGF)-ß1, TGF-ß2, Interleukin-6 (IL-6), IL-10, VEGF and glial fibrillary acidic protein (GFAP), some of which have been studied more intensely than others. The present paper tried to summarize, highlight and cross-correlate the major findings made in the last decade on the function of these genes and their association with different types of cells, genes and gene expression products in the ERM formation.

The Proteins of Keratoconus: a Literature Review Exploring Their Contribution to the Pathophysiology of the Disease.

INTRODUCTION: Keratoconus (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. METHODS: PubMed, 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. RESULTS: A 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. CONCLUSION: The 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.

Genetic Aspects of Keratoconus: A Literature Review Exploring Potential Genetic Contributions and Possible Genetic Relationships with Comorbidities.

INTRODUCTION: Keratoconus (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. METHODS: The 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. RESULTS: An 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. CONCLUSION: Twenty-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.