Progressive Keratoconus in a Patient With Severe Pectus Excavatum and a Cartilage Oligomeric Matrix Protein Gene Mutation: A Case Report.

INTRODUCTION: Keratoconus is a progressive ocular disorder associated with numerous systemic diseases, many of which affect the musculoskeletal system. Although the etiology and pathophysiology of the disorder remain elusive, recent studies suggest a significant role of genetic predisposition in the pathogenesis of keratoconus. This case report aims to elucidate a potential genetic association in a patient presenting with keratoconus, severe pectus excavatum, generalized muscular weakness, and skeletal deformities. CASE DESCRIPTION: A 31-year-old Iranian man presented with progressively diminishing vision in both eyes over the years, eventually diagnosed with keratoconus. The patient's history and further examination indicated generalized muscular weakness, skeletal deformities, and severe pectus excavatum with cardiac and large vessel displacement. Whole-exome sequencing identified two heterozygous gene variants: one in the Cartilage Oligomeric Matrix Protein (COMP) gene and another in the Regulating Synaptic Membrane Exocytosis 1 gene. The patient's systemic and ocular symptoms, combined with the gene variants identified, suggested a connective tissue systemic disorder, potentially within the clinical spectrum of COMPopathies. CONCLUSION: This is the first documented case of bilateral progressive keratoconus associated with severe pectus excavatum, generalized musculoskeletal dystrophy, and a COMP gene mutation. It highlights the necessity of continued search into the pathogenic genes of keratoconus, particularly in cases with coexisting systemic manifestations, to further our understanding of the etiology and pathogenesis of this complex disease.

Systematic review of sample size calculations and reporting in randomized controlled trials in ophthalmology over a 20-year period.

PURPOSE: Randomized Controlled Trials (RCTs) are considered the gold standard for the practice of evidence-based medicine. The purpose of this study is to systematically assess the reporting of sample size calculations in ophthalmology RCTs in 5 leading journals over a 20-year period. Reviewing sample size calculations in ophthalmology RCTs will shed light on the methodological quality of RCTs and, by extension, on the validity of published results. METHODS: The MEDLINE database was searched to identify full reports of RCTs in the journals Ophthalmology, JAMA Ophthalmology, American Journal of Ophthalmology, Investigative Ophthalmology and Visual Science, and British Journal of Ophthalmology between January and December of the years 2000, 2010 and 2020. Screening identified 559 articles out of which 289 met the inclusion criteria for this systematic review. Data regarding sample size calculation reporting and trial characteristics was extracted for each trial by independent investigators. RESULTS: In 2020, 77.9% of the RCTs reported sample size calculations as compared with 37% in 2000 (p < 0.001) and 60.7% in 2010 (p = 0.012). Studies reporting all necessary parameters for sample size recalculation increased significantly from 17.2% in 2000 to 39.3% in 2010 and 43.0% in 2020 (p < 0.001). Reporting of funding was greater in 2020 (98.8%) compared with 2010 (89.3%) and 2000 (53.1%). Registration in a clinical trials database occurred more frequently in 2020 (94.2%) compared to 2000 (1.2%; p < 0.001) and 2010 (68%; p < 0.001). In 2020, 38.4% of studies reported different sample sizes in the online registry from the published article. Overall, the most studied area in 2000 was glaucoma (29.6% of RCTs), whereas in 2010 and 2020, it was retina (40.2 and 37.2% of the RCTs, respectively). The number of patients enrolled in a study and the number of eyes studied was significantly greater in 2020 compared to 2000 and 2010 (p < 0.001). CONCLUSION: Sample size calculation reporting in ophthalmology RCTs has improved significantly between the years 2000 and 2020 and is comparable to other fields in medicine. However, reporting of certain parameters remains inconsistent with current publication guidelines.

Wavelike Interface Opacities After Descemet-Stripping Automated Endothelial Keratoplasty: 7-Year Follow-up.

PURPOSE: To report a case of wavelike interface opacities in a patient who underwent Descemet-stripping automated endothelial keratoplasty (DSAEK) and was managed conservatively over the course of 7 years. METHODS: A 65-year-old woman underwent DSAEK for pseudophakic bullous keratopathy. Textural wavelike opacities were noted in the graft-host interface 6 days postoperatively without evidence of anterior segment inflammation. The patient's vision was also initially limited by the presence of cystoid macular edema (CME). Six months postoperatively, CME had resolved but the patient's vision failed to improve better than 20/80 because of the persistent dense interface opacities. The patient refused to undergo graft exchange despite a suboptimal visual result and she therefore was observed over time. RESULTS: The interface opacities started to regress and her visual acuity improved to 20/30 by 9 months postoperatively. The opacities became gradually less prominent over the next few years, and at 7 years postoperatively, her best-corrected vision was 20/25. CONCLUSION: In this case, observation of this post-DSAEK complication rather than surgical intervention resulted in a favorable long-term visual outcome.

Human Papilloma Virus Infection Does Not Predict Response to Interferon Therapy in Ocular Surface Squamous Neoplasia.

PURPOSE: To identify the frequency of human papilloma virus (HPV) in ocular surface squamous neoplasia (OSSN) and to evaluate differences in clinical features and treatment response of tumors with positive versus negative HPV results. DESIGN: Retrospective case series. PARTICIPANTS: Twenty-seven patients with OSSN. METHODS: Ocular surface squamous neoplasia specimens were analyzed for the presence of HPV. Clinical features and response to interferon were determined retrospectively and linked to the presence (versus absence) of HPV. MAIN OUTCOME MEASURES: Clinical characteristics of OSSN by HPV status. RESULTS: Twenty-one of 27 tumors (78%) demonstrated positive HPV results. The HPV genotypes identified included HPV-16 in 10 tumors (48%), HPV-31 in 5 tumors, HPV-33 in 1 tumor, HPV-35 in 2 tumors, HPV-51 in 2 tumors, and a novel HPV in 3 tumors (total of 23 tumors because 1 tumor had 3 identified genotypes). Tumors found in the superior limbus were more likely to show positive HPV results (48% vs. 0%; P=0.06, Fisher exact test). Tumors with positive HPV-16 results were larger (68 vs. 34 mm2; P=0.08, Mann-Whitney U test) and were more likely to have papillomatous morphologic features (50% vs. 12%; P=0.07, Fisher exact test) compared with tumors showing negative results for HPV-16. Human papilloma virus status was not found to be associated with response to interferon therapy (P=1.0, Fisher exact test). Metrics found to be associated with a nonfavorable response to interferon were male gender and tumors located in the superior conjunctivae. CONCLUSIONS: The presence of HPV in OSSN seems to be more common in lesions located in the nonexposed, superior limbus. Human papilloma virus presence does not seem to be required for a favorable response to interferon therapy.

Quantum Molecular Resonance Electrotherapy for the Treatment of Pediatric Ocular Rosacea.

PURPOSE: The purpose of this study was to report the outcomes of quantum molecular resonance (QMR) electrotherapy in the management of refractory pediatric ocular rosacea. METHODS: This is a retrospective case series on 3 female pediatric patients (ages 12, 15, 14 years) with ocular rosacea. Two patients presented with corneal stromal neovascularization and punctate epithelial erosions while 1 patient presented with corneal scarring and paracentral stromal thinning. After failing conservative management, the patients were treated with 4 consecutive QMR electrotherapy sessions with the intensity set at 5 corresponding on average to a power of 12 W, with 60 V voltage and 200 mA current. Informed consent was obtained for off-label use. Patients were assessed for changes in vision, foreign body sensation, tearing, photophobia, and redness at each visit to determine symptomatic improvement. Outcome measures include best-corrected visual acuity, use of supplemental therapies (eg topical steroids) for symptom relief, extent of corneal neovascularization via serial slitlamp photography, and corneal scar remodeling via high resolution anterior segment optical coherence tomography (OCT). RESULTS: Two of the 3 patients experienced improvement in visual acuity after QMR electrotherapy. Corneal neovascularization and scarring regressed significantly in all 3 patients. Two months post-QMR electrotherapy, corneal remodeling was evident on optical coherence tomography in 2 patients. All 3 patients were able to discontinue topical immunosuppressants and remain symptom-free at 1.5 years of follow-up. CONCLUSIONS: QMR electrotherapy is a promising alternative in the treatment of refractory ocular rosacea in childhood and puberty, and it may potentiate corneal remodeling.

A Rare Manifestation of Discoid Lupus Erythematosus Solely in the Lower Eyelid of a Young Man.

Discoid lupus erythematosus (DLE)-associated edema and erythema on the lower eyelid as the only manifestation of the disease is a rare clinical entity. Persistent discoid lupus-related lower eyelid manifestations are challenging to diagnose, can be mistaken for blepharitis or malignancies, and often require histopathological evaluation. If left untreated, the condition can progress, among others, to conjunctival scarring or symblepharon formation. Thus, early identification and management of the disease entity is of the utmost significance. We present a rare case of a young patient with enduring, unilateral lower eyelid edema and erythema that had been managed as blepharitis for several years. No other related cutaneous involvement was detected on the eyelids, face, or body. Following a lower eyelid biopsy and histopathological assessment, the patient was diagnosed with underlying DLE. This case report reviews the previous literature, discusses a differentiation strategy from other relevant pathologies, such as blepharitis and sebaceous cell carcinoma, and highlights the implemented diagnostic procedures.

Outcomes of Combined Penetrating Keratoplasty and Limbal Stem Cell Transplantation: A Meta-Analysis on Simultaneous Versus Sequential Surgery.

PURPOSE: The objective of this study is to perform a systematic review and meta-analysis of the published studies on limbal stem cell transplantation (LSCT) combined with penetrating keratoplasty (PK) performed either simultaneously or sequentially. METHODS: An extensive search was conducted in the MEDLINE and Google Scholar databases. Prospective and retrospective trials and case series reporting on the outcomes of LSCT with PK were included. Primary outcomes were the stability of the ocular surface and the rejection and/or failure of the corneal graft. RESULTS: A total of 209 eyes from 13 studies were included in the simultaneous group and 489 eyes from 33 studies in the sequential group. Ocular surface stability was 88% [95% confidence interval (CI), 79%-96%] for sequential cases and 64% (95% CI, 43%-82%) for simultaneous cases ( P = 0.001). The graft failure rate was 15% (95% CI, 6%-26%) for sequential cases and 44% (95% CI, 31%-58%) for simultaneous cases ( P < 0.001). For cases performed sequentially, subgroup analysis revealed a stable ocular surface in 97% (95% CI, 91%-100%) of autograft cases and 63% (95% CI, 45%-80%) of allograft cases ( P < 0.001). The graft failure rate in sequential cases was 7% (95% CI, 0%-18%) for autografts and 34% (95% CI, 18%-52%) for allografts ( P < 0.001). CONCLUSIONS: Sequential LSCT followed by PK demonstrated superior results in terms of ocular surface stability and graft retention compared with simultaneous LSCT and PK. Limbal stem cells of autologous origin fare better than allogeneic ones in sequential cases.

Semi-Autologous Corneal Transplantation with Simultaneous Bilateral Surgery: A Case Report.

The present report describes a case of semi-autologous corneal transplantation with bilateral surgery using two operating microscopes simultaneously. An 86-year-old man with history of six prior failed penetrating keratoplasties in his right eye presented with decreased vision. His other eye was deeply amblyopic but had a clear 30-year-old Castroviejo-square graft with an endothelial cell count of 803 cells/mm2. A semi-autologous graft was performed from the left eye to the right. Surgery was performed simultaneously on both eyes by two different surgeons using a standard ophthalmic operating microscope as well as a second ENT microscope. Upon trephination of the right failed corneal graft, vitreous opacities were noted and sent for culture. The semi-autologous tissue was directly transferred from the left eye to the right without any storage in preservation media to avoid endothelial cell loss. The semi-autologous graft remained clear in the immediate postoperative period. However, the vitreous cultures grew coagulase-negative Staphylococcus. Despite all efforts, the patient eventually developed a retinal detachment and vision in the right eye decreased to light perception. Autologous penetrating keratoplasty is an option for patients with loss of corneal function in a potentially seeing eye and a clear cornea in a contralateral eye with poor visual potential due to non-corneal disease. This case is unique in that part of the autologous penetrating keratoplasty had an old square graft in the center and corneal transplant surgery was done simultaneously in both eyes. It also highlights chronic indolent endophthalmitis as a potential cause of multiple graft failures.

Genetic analysis of selenocysteine biosynthesis in the archaeon Methanococcus maripaludis.

In Archaea selenocysteine (Sec) is synthesized in three steps. First seryl-tRNA synthetase acylates tRNA(Sec) with serine to generate Ser-tRNA(Sec). Then phosphoseryl-tRNA(Sec) kinase (PSTK) forms Sep-tRNA(Sec) , which is converted to Sec-tRNA(Sec) by Sep-tRNA:Sec-tRNA synthase (SepSecS) in the presence of selenophosphate produced by selenophosphate synthetase (SelD). A complete in vivo analysis of the archaeal Sec biosynthesis pathway is still unavailable, and the existence of a redundant pathway or of a rescue mechanism based on the conversion of Sep-tRNA(Sec) to Cys-tRNA(Sec) during selenium starvation, cannot be excluded. Here we present a mutational analysis of Sec biosynthesis in Methanococcus maripaludis strain Mm900. Sec formation is abolished upon individually deleting the genes encoding SelD, PSTK or SepSecS; the resulting mutant strains could no longer grow on formate while growth with H(2) + CO(2) remained unaffected. However, deletion of the PSTK and SepSecS genes was not possible unless the selenium-free [NiFe]-hydrogenases Frc and Vhc were expressed. This required the prior deletion of either the gene encoding SelD or that of HrsM, a LysR-type regulator suppressing transcription of the frc and vhc operons in the presence of selenium. These results show that M. maripaludis Mm900 is facultatively selenium-dependent with a single pathway of Sec-tRNA(Sec) formation.

Ophthalmic artery chemosurgery for the management of retinoblastoma in eyes with extensive (>50%) retinal detachment.

BACKGROUND: Superselective delivery of chemotherapy through the ophthalmic artery, i.e. ophthalmic artery chemosurgery, has been used for the treatment of advanced intraocular retinoblastoma. Herein, we evaluate the efficacy of ophthalmic artery chemosurgery for retinoblastoma associated with >50% retinal detachment. PROCEDURE: Retrospective review of 37 eyes of 34 retinoblastoma patients who had extensive (>50%) bullous non-rhegmatogenous retinal detachments and received ophthalmic artery chemosurgery either as primary treatment or as "salvage" treatment after failed multi-cycle intravenous chemotherapy and/or external beam radiation (mean follow-up, 21 months). Data on patient and ocular survival, complications of ophthalmic artery chemosurgery treatments, time course of retinal reattachment, and serial electroretinograms (ERG) were collected. RESULTS: A total of 134 ophthalmic artery chemosurgery injections were performed. All children survive. Five eyes (5/37; 14%) were enucleated for progression of disease. The Kaplan-Meier enucleation-free survival rate at 2 years was 87.9% (95% confidence interval, 76.5-99.3%). The retina reattached in 28 eyes (28/37; 76%) and the 30-Hz flicker ERGs improved by >25 µV in seven eyes (7/37; 19%), remained stable (change < 25 µV) in 26 eyes (26/37; 70%), and decreased by >25 µV in four eyes (4/37; 11%). The Kaplan-Meier retinal reattachment rate was 58% after 3 months and three ophthalmic artery chemosurgery infusions (95% confidence interval, 41.9-74.1%). CONCLUSIONS: Ophthalmic artery chemosurgery is effective in preventing enucleation, promoting retinal reattachment and preserving or improving retinal function in the majority of eyes with advanced retinoblastoma and >50% retinal detachment that would otherwise be considered for enucleation.

The canonical pathway for selenocysteine insertion is dispensable in Trypanosomes.

The micronutrient selenium is found in proteins as selenocysteine (Sec), the 21st amino acid cotranslationally inserted in response to a UGA codon. In vitro studies in archaea and mouse showed that Sec-tRNA(Sec) formation is a 3-step process starting with serylation of tRNA(Sec) by seryl-tRNA synthetase (SerRS), phosphorylation of serine to form phosphoserine (Sep)-tRNA(Sec) by phosphoseryl-tRNA(Sec) kinase (PSTK), and conversion to Sec-tRNA(Sec) by Sep-tRNA:Sec-tRNA synthase (SepSecS). However, a complete study of eukaryotic selenoprotein synthesis has been lacking. Here, we present an analysis of Sec-tRNA(Sec) formation in the parasitic protozoon Trypanosoma brucei in vivo. Null mutants of either PSTK or SepSecS abolished selenoprotein synthesis, demonstrating the essentiality of both enzymes for Sec-tRNA(Sec) formation. Growth of the 2 knockout strains was not impaired; thus, unlike mammals, trypanosomes do not require selenoproteins for viability. Analysis of conditional RNAi strains showed that SerRS, selenophosphate synthase, and the Sec-specific elongation factor, EFSec, are also essential for selenoprotein synthesis. These results with T. brucei imply that eukaryotes have a single pathway of Sec-tRNA(Sec) synthesis that requires Sep-tRNA(Sec) as an intermediate.

Ab Interno Goniotomy with the Kahook Dual Blade in a Monocular Patient with Mucous Membrane Pemphigoid and Refractory Open Angle Glaucoma: A Case Report.

Purpose: To describe the case of a monocular patient with ocular mucous membrane pemphigoid (MMP) and open angle glaucoma refractory to medical treatment, who was successfully managed with ab interno goniotomy at the time of cataract surgery. Methods: A 63-year-old woman with a history of severe MMP presented with exacerbation of the disease in both eyes. Vision was 20/80 in the right eye and light perception in the left eye. Symblepharon formation, trichiasis and forniceal foreshortening were present in the right eye, while the cornea of the left eye was completely conjunctivalized. Following aggressive systemic immunosuppressive therapy with corticosteroids and cyclophosphamide, the disease was brought under control. However, the patient developed a mature cataract and high intraocular pressure (IOP) of 28 mmHg on maximal medical therapy. Due to the high risk of ocular MMP exacerbation with glaucoma filtration surgery, the decision was made to proceed with cataract extraction combined with ab interno goniotomy with the Kahook Dual Blade. Results: There were no intraoperative complications. The IOP has remained in the 12-14 mmHg range without any topical glaucoma medications over a total follow up of 3.5 years. Conclusion: Ab interno goniotomy using the Kahook Dual Blade can significantly reduce IOP and medication burden in MMP cases, where any type of conjunctival incisional surgery could induce disease flare up. In this case, it represented a safe and effective surgical procedure for ocular MMP with concomitant refractory open angle glaucoma.

Paraneoplastic Pemphigus Associated with Bilateral Corneal Perforations in Follicular Dendritic Cell Sarcoma.

PURPOSE: To describe a case of paraneoplastic pemphigus (PNP) presenting as spontaneous bilateral corneal perforations in a patient with follicular dendritic cell sarcoma. METHODS: Retrospective chart reviewResults: A 73-year-old Greek woman with a history of follicular dendritic cell sarcoma (FDCS) presented with bilateral corneal perforations and a cicatrizing conjunctivitis. Her diagnosis was consistent with PNP with corneal and conjunctival involvement after a change in her chemotherapy regimen from intravenous cyclophosphamide to gemcitabine. She was treated with a multilayered amniotic membrane in the right eye and cyanoacrylate glue in the left eye. Systemic intravenous cyclophosphamide and oral prednisone were re-started. Both perforations healed but the patient passed away soon after precluding further follow-up. CONCLUSIONS: Ocular manifestations of PNP can rarely present with spontaneous corneal perforations. This is the first case of FDCS-associated PNP with corneal involvement. Such cases should be diagnosed expediently and managed with aggressive systemic immunosuppressive therapy.

Quality control despite mistranslation caused by an ambiguous genetic code.

A high level of accuracy during protein synthesis is considered essential for life. Aminoacyl-tRNA synthetases (aaRSs) translate the genetic code by ensuring the correct pairing of amino acids with their cognate tRNAs. Because some aaRSs also produce misacylated aminoacyl-tRNA (aa-tRNA) in vivo, we addressed the question of protein quality within the context of missense suppression by Cys-tRNA(Pro), Ser-tRNA(Thr), Glu-tRNA(Gln), and Asp-tRNA(Asn). Suppression of an active-site missense mutation leads to a mixture of inactive mutant protein (from translation with correctly acylated aa-tRNA) and active enzyme indistinguishable from the wild-type protein (from translation with misacylated aa-tRNA). Here, we provide genetic and biochemical evidence that under selective pressure, Escherichia coli not only tolerates the presence of misacylated aa-tRNA, but can even require it for growth. Furthermore, by using mass spectrometry of a reporter protein not subject to selection, we show that E. coli can survive the ambiguous genetic code imposed by misacylated aa-tRNA tolerating up to 10% of mismade protein. The editing function of aaRSs to hydrolyze misacylated aa-tRNA is not essential for survival, and the EF-Tu barrier against misacylated aa-tRNA is not absolute. Rather, E. coli copes with mistranslation by triggering the heat shock response that stimulates nonoptimized polypeptides to achieve a native conformation or to be degraded. In this way, E. coli ensures the presence of sufficient functional protein albeit at a considerable energetic cost.

Endothelial Biopsy for the Diagnosis and Management of Culture-Negative Retrocorneal Fungal Keratitis With the Assistance of Optical Coherence Tomography Imaging.

PURPOSE: To report a case of a culture-negative deep fungal corneal infection that was diagnosed after histopathology of an anterior segment optical coherence tomography-guided endothelial biopsy. METHODS: A 22-year-old woman with history of contact lens wear and concomitant topical steroid use presented with a mid-stromal corneal infiltrate that failed to respond to oral acyclovir and topical fortified antibiotics. Although cornea stains, cultures, and confocal microscopy showed negative results, there was high clinical suspicion for fungal keratitis. After 2 months on topical natamycin, oral voriconazole, and serial intrastromal and intracameral voriconazole injections, the infiltrate enlarged and deepened. Imaging with anterior segment optical coherence tomography revealed that the infection had progressed to an endothelial plaque. RESULTS: Diagnostic endothelial biopsy was performed in the operating room. Cultures showed again negative results, whereas histopathology of the removed specimen revealed fungal elements. The postoperative edema at the site of the biopsy resolved over the course of 4 weeks, and a posterior stromal scar formed. Serial intrastromal and intracameral voriconazole injections were continued for the first postoperative month. At the 1-year and the 3-year follow-up examinations, the patient's vision was 20/20 without recurrence. CONCLUSIONS: Intraoperative scraping of the endothelial plaque and histopathologic evaluation of the specimen proved to be of utmost importance for definitive diagnosis and resolution of the culture-negative deep fungal infection in this case. This young patient's cornea was retained and vision remains excellent.

Cost-Benefit Analysis of Single versus Repeated Use of Single-Use Devices in Cataract Surgery.

PURPOSE: To estimate the net cost effect associated with the real-world practice of repeated use of designated single-use medical devices (SUDs) versus their proper single use in cataract surgery in Greece. DESIGN: A cost-benefit analysis model was constructed in the form of a decision tree. METHODS: A digital expert panel was assembled in order to estimate the probabilities of intraoperative and postoperative complications associated with single and repeated use of SUDs. Unit costs for the management of each complication were obtained from the official Greek bulletins. A Monte Carlo-type sensitivity analysis was performed to assess the robustness of the results. RESULTS: Based on the probabilities of complications attained from the expert panel, repeated use of SUDs is associated with a higher chance of complications compared to single use, which results in higher cost of complication management. Under the healthcare sector perspective, the total expected cost per cataract surgery is 1,403.98€ (1,244.20€ the initial cost of cataract surgery plus 159.78€ the cost of adverse events) in the case of single use, while for repeated use the total cost is 1,486.29€ (1,146.86€ + 339.43€, respectively) and, thus, repeated use of SUDs in cataract surgery results in 82.31€ higher expected cost per patient compared to their single use. Moreover, the societal perspective analysis indicated even higher additional costs in the case of SUD reuse (108.24€). CONCLUSION: Repeated use of SUDs in cataract surgery is not appropriate, it jeopardizes patient safety and carries a legal liability for the reuser. The present study, which is the first to attach a monetary value to the common yet questionable practice of SUD reuse, shows that it is not cost beneficial. Therefore, it is expected that the results will have implications in policy formulations to improve the delivery of cataract healthcare.

Human SepSecS or SLA/LP: selenocysteine formation and autoimmune hepatitis.

Selenocysteine, the 21st genetically encoded amino acid, is the major form of the antioxidant trace element selenium in the human body. In eukaryotes and archaea its synthesis proceeds through a phosphorylated intermediate in a tRNA-dependent fashion. The final step of selenocysteine formation is catalyzed by O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS) that converts phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec). The human SepSecS protein is also known as soluble liver antigen/liver pancreas (SLA/LP), which represents one of the antigens of autoimmune hepatitis. Here we review the discovery of human SepSecS and the current understanding of the immunogenicity of SLA/LP in autoimmune hepatitis.

Structural insights into RNA-dependent eukaryal and archaeal selenocysteine formation.

The micronutrient selenium is present in proteins as selenocysteine (Sec). In eukaryotes and archaea, Sec is formed in a tRNA-dependent conversion of O-phosphoserine (Sep) by O-phosphoseryl-tRNA:selenocysteinyl-tRNA synthase (SepSecS). Here, we present the crystal structure of Methanococcus maripaludis SepSecS complexed with PLP at 2.5 A resolution. SepSecS, a member of the Fold Type I PLP enzyme family, forms an (alpha2)2 homotetramer through its N-terminal extension. The active site lies on the dimer interface with each monomer contributing essential residues. In contrast to other Fold Type I PLP enzymes, Asn247 in SepSecS replaces the conserved Asp in binding the pyridinium nitrogen of PLP. A structural comparison with Escherichia coli selenocysteine lyase allowed construction of a model of Sep binding to the SepSecS catalytic site. Mutations of three conserved active site arginines (Arg72, Arg94, Arg307), protruding from the neighboring subunit, led to loss of in vivo and in vitro activity. The lack of active site cysteines demonstrates that a perselenide is not involved in SepSecS-catalyzed Sec formation; instead, the conserved arginines may facilitate the selenation reaction. Structural phylogeny shows that SepSecS evolved early in the history of PLP enzymes, and indicates that tRNA-dependent Sec formation is a primordial process.

Management of Stromal Herpes Simplex Virus Keratitis With Epithelial Ulceration Using Optical Coherence Tomography-Generated Corneal Thickness Maps.

PURPOSE: To report 2 cases of herpes simplex virus (HSV) stromal keratitis with epithelial ulceration that were managed using optical coherence tomography-generated pachymetric and corneal epithelial thickness maps. METHODS: Two patients with a history of HSV keratitis with nonhealing epithelial defects were referred to the Athens Vision Eye Institute. Anterior segment optical coherence tomography-generated pachymetric and corneal epithelial thickness maps showed subclinical stromal edema and irregular epithelium, thus indicating diagnoses of HSV stromal keratitis with epithelial ulceration. The patients were administered topical preservative-free dexamethasone and oral antiviral therapy. Steroid tapering was guided by pachymetric and corneal epithelial thickness maps at each follow-up visit. RESULTS: Both patients experienced initial healing of the epithelium and resolution of stromal inflammation. One patient had a recurrence of HSV stromal keratitis with epithelial defect 3 months after initial improvement, with pachymetric and corneal epithelial thickness maps indicating subclinical stromal edema. He was reintroduced to topical steroid therapy, and the stromal edema and epithelial defect subsequently resolved. Both patients have had no recurrences in the past year. CONCLUSIONS: Pachymetric and corneal epithelial thickness maps provide an objective assessment of stromal inflammation and the following 2 clinical advantages in the management of HSV stromal keratitis with epithelial ulceration: (1) they help differentiate it from HSV epithelial keratitis with geographic ulceration and neurotrophic keratopathy and (2) offer objective measurements to guide management with topical corticosteroids until resolution of stromal edema. Thus, treatment can be initiated in a timely manner, and the blinding complications of HSV stromal keratitis can be avoided.