The trace element selenium is found in proteins as selenocysteine (Sec), the 21st amino acid to participate in ribosome-mediated translation. The substrate for ribosomal protein synthesis is selenocysteinyl-tRNA ^Sec . Its biosynthesis from seryl-tRNA ^Sec has been established for bacteria, but the mechanism of conversion from Ser-tRNA ^Sec remained unresolved for archaea and eukarya. Here, we provide evidence for a different route present in these domains of life that requires the tRNA ^Sec -dependent conversion of O -phosphoserine (Sep) to Sec. In this two-step pathway, O -phosphoseryl-tRNA ^Sec kinase (PSTK) converts Ser-tRNA ^Sec to Sep-tRNA ^Sec . This misacylated tRNA is the obligatory precursor for a Sep-tRNA:Sec-tRNA synthase (SepSecS); this protein was previously annotated as SLA/LP. The human and archaeal SepSecS genes complement in vivo an Escherichia coli Sec synthase (SelA) deletion strain. Furthermore, purified recombinant SepSecS converts Sep-tRNA ^Sec into Sec-tRNA ^Sec in vitro in the presence of sodium selenite and purified recombinant E. coli selenophosphate synthetase (SelD). Phylogenetic arguments suggest that Sec decoding was present in the last universal common ancestor. SepSecS and PSTK coevolved with the archaeal and eukaryotic lineages, but the history of PSTK is marked by several horizontal gene transfer events, including transfer to non-Sec-decoding Cyanobacteria and fungi.

Purpose: To present the molecular mechanisms involved in the pathogenesis of conjunctival melanoma (CM) and review the existing literature on targeted molecular inhibitors as well as immune checkpoint inhibitors for the management of locally advanced and metastatic disease. Methods: A comprehensive review of the literature was performed using the keywords “conjunctival melanoma”, “immune checkpoint inhibitors”, “BRAF inhibitors”, “MEK inhibitors”, “CTLA4 inhibitors”, “PD1 inhibitors”, “c-KIT mutations”, “BRAF mutations”, “NRAS mutations”, “dabrafenib”, “trametinib”, “vemurafenib”, “ipilimumab”, “pembrolizumab”, and “nivolumab”. A total of 250 articles were reviewed and 120 were included in this report. Results: Mutations of mediators in the MAP kinase pathway, such as RAS, BRAF, MEK and ERK, and mutations of the PI3K/AKT/mTOR pathway play a major role in the pathogenesis of conjunctival melanoma. In addition, alterations of c-KIT, NF1, TERT, chemokine receptors as well as chromosomal copy number alterations and micro RNAs are thought to have a causative association with CM development. Targeted molecular inhibitors, such as BRAF and MEK inhibitors, are currently being implemented in the therapy of BRAF-mutated CM. Furthermore, immune checkpoint PD-1 and CTLA4 inhibitors with favorable clinical outcomes in the treatment of cutaneous melanoma have increased recurrence-free survival and reduced metastatic spread in CM cases. Conclusion: The complex molecular mechanisms that contribute to the development of CM can be targeted both by molecular inhibitors of oncogenic pathways as well as immune checkpoint inhibitors in order to halt progression of the disease and increase survival.

Purpose: Stenotrophomonas maltophilia, an uncommon cause of infectious keratitis, is difficult to treat because of its resistance to multiple antibiotics. The purpose of this study is to describe the clinical features, antibiotic susceptibility profile, and outcomes of S. maltophilia keratitis. Methods: A retrospective review of records from 1987 to 2016 identified 26 eyes of 26 patients who were treated at the Bascom Palmer Eye Institute for an S. maltophilia corneal ulcer. Clinical data were analyzed as to predisposing factors, clinical presentation, antibiotic susceptibility, treatment selection, and clinical outcomes. Results: Median age at presentation was 65 years (range, 16–98). Twelve patients were using topical corticosteroids, 8 patients had a history of penetrating keratoplasty, and 9 were contact lens wearers. All patients received topical antibiotics, 2 required therapeutic penetrating keratoplasty, and 1 was enucleated. At presentation, 57.7% (15/26) of the patients had visual acuity of 20/400 or worse. At the final visit, only 30.4% (7/23) of the patients had visual acuity worse than 20/400, whereas 65.2% (15/23) of the patients had 20/100 or better. Almost all isolates (25/26, 96.2%) were susceptible to fluoroquinolones and 77.3% (17/22) of them to polymyxin B/trimethoprim. Only 33.3% (5/15) of the tested isolates were susceptible to aminoglycosides and 58.3% (7/12) to cephalosporins. Conclusions: Infectious keratitis due to S. maltophilia presents a treatment challenge because of its resistance to aminoglycosides and cephalosporins, which are typically used for empiric broad-spectrum gram-negative coverage as fortified solutions. Fluoroquinolones and polymyxin B/trimethoprim should be considered instead in cases of S. maltophilia infection.

To report a case of bilateral benign reactive lymphoid hyperplasia (BRLH) of the conjunctiva treated with oral doxycycline and perform review of the literature evaluating the presentation, treatment and risk of transformation to lymphoma. A case report is described and review of the literature from January 1975 to January 2019 was performed. A 30-year-old man presented with bilateral enlarging fleshy pink medial canthal conjunctival lesions. Incisional biopsy revealed BRLH. Oral doxycycline was initiated (100 mg two times a day) for a total of 2 months. Both lesions decreased in size significantly at the patient’s two-month follow up visit. The residual lesion in the right eye was excised along with an adjacent pterygium and the patient has been free of recurrence for the past 1.5 years. The lesion in the left eye has remained stable in size after cessation of the oral doxycycline. A total of 235 cases of conjunctival BRLH were identified in our literature search. The mean age at diagnosis was 35.2 years (range, 5 to 91 years). BRLH lesions were unilateral in 75% of patients and bilateral in 25% of them. Seven patients (2.9%) had a concurrent Epstein-Barr virus (EBV) infection at the time of lesion appearance. The most common treatments were surgical excision (155/235 or 65.9%) and corticosteroids (30/235 or 12.7%), while 14% (33/235) of the patients were observed and 4.6% (11/235) received external beam radiotherapy alone. Recurrence occurred in ten patients (10/235 or 4.2%), of whom five had undergone surgical excision alone, two excision followed by external beam radiotherapy, one excision and oral corticosteroids, one radiotherapy alone and one had been treated with topical corticosteroids. Overall, only 2 of the 235 reported cases (0.8%) developed malignancy, one localized to the conjunctiva and one systemic. Benign reactive lymphoid hyperplasia is one of the lymphoproliferative disorders of the conjunctiva and ocular adnexa. Extensive literature review shows that most cases are treated with surgery, steroids or observation. Oral doxycycline may be considered an alternative non-invasive treatment of BRLH conjunctival lesions. BRLH lesions warrant careful follow up as they can rarely transform into conjunctival or systemic lymphoma.

Objective To assess the impact of a 5 min interactive online survey on raising awareness about cornea donation and willingness to become a donor. Methods An interactive online questionnaire was used to collect information regarding awareness, perceptions and attitudes towards cornea donation and to educate the participants about the process and value of cornea donation. Willingness to become a cornea donor was assessed at the beginning and the end of the survey. Results The survey was completed by 1769 Greek residents. Willingness to become a cornea donor increased from 40.5% (n=717) at the beginning of the survey to 55.2% (n=977) by the end of it (p<0.00001). Younger participants, those whose work or studies were unrelated to the medical field, and those with the least knowledge about cornea donation and transplantation were more likely to change their views towards donation by the end of the survey (42.3%, 44.8% and 82.1% increase in willingness to donate, respectively). Major deterrents to donation were lack of information, concerns about the use of the donated corneas and corruption within the medical field. Conclusion Our 5 min online survey had a significant impact on changing the mentality towards cornea donation in Greece. We live in an online era and incorporation of online tools and applications in awareness campaigns towards cornea and organ donation has become a necessity.

To report a case of corneal hydrops in a patient with keratoglobus that was managed with endothelial keratoplasty to achieve corneal stability and prevent a limbus-to-limbus tear in Descemet membrane. A 30-year-old man with keratoglobus presented with corneal hydrops in his left eye resulting from a central vertical tear in Descemet membrane. His other eye had been previously treated with penetrating keratoplasty using a large graft (an 11-mm donor graft to a 10-mm recipient bed) because of a limbus-to-limbus tear in Descemet membrane without resolution of his edema. An attempt to approximate the edges of the Descemet tear in the left eye by an intracameral air injection failed, and the tear continued to progress peripherally. An endothelial keratoplasty button with anchoring sutures was placed over the Descemet tear because of excessive localized edema. One month after insertion of the sutured endothelial keratoplasty button, the edema had resolved, and 1 year later, the tear remains sealed. The patient's visual acuity improved from counting fingers at 1 foot to 20/100. Reconstitution of the posterior corneal surface in keratoglobus-induced hydrops can be achieved with endothelial keratoplasty over the Descemet tear. Preventing progression of a central Descemet tear is essential to bypass the need for a large-diameter penetrating keratoplasty graft and its complications in a young patient with a history of bilateral corneal hydrops.