RETINAL FINDINGS IN PRESUMED INFECTIOUS POSTERIOR UVEITIS AND CORRELATION WITH POLYMERASE CHAIN REACTION RESULTS.

PURPOSE: To correlate demographics, retinal lesion characteristics, and host immune status with the pathogen found on polymerase chain reaction analysis of aqueous fluid in patients with suspected infectious posterior uveitis. METHODS: Medical records of patients who underwent anterior chamber paracentesis for suspected infectious posterior uveitis and had retinal photographs between 2014 and 2016 at a single institution were reviewed. Data collection included demographics, clinical appearance of the lesions, and polymerase chain reaction results. Fundus photographs were evaluated by two masked observers for the clinical features of the retinitis. RESULTS: Twenty-eight patients were included in the study. There was substantial to almost perfect agreement on retinitis location (κ = 0.67) and number (κ = 0.76) between the masked photograph graders. Polymerase chain reaction results were positive for herpes simplex virus or varicella zoster virus in 43%, cytomegalovirus in 11%, and toxoplasmosis in 3%; 43% had negative polymerase chain reaction results. Detection of herpes simplex virus or varicella zoster virus on polymerase chain reaction of the aqueous was associated with paucifocal lesions (82%, P = 0.021) and lesions involving the peripheral retina (91%, P = 0.023), consistent with the diagnosis of acute retinal necrosis. CONCLUSION: These data suggest that the diagnosis of acute retinal necrosis can be reasonably inferred on clinical examination, providing a guide for initial empiric therapy.

Intercuneiform and Lisfranc Fracture-Dislocation Due to Seizure: A Case Report.

Cuneiform dislocation associated with Lisfranc injury is a very rare injury. Dislocation over the midfoot due to a seizure has not been previously reported in published studies. A 35-year-old female presented with an intercuneiform dislocation and Lisfranc fracture-dislocation after a generalized seizure. Immediate close reduction of the dorsally dislocated cuneiforms was performed, followed by definitive treatment to restore the foot arches. A proposed underlying pathophysiology of dislocation due to seizure in terms of the biomechanics is discussed. The purpose of our report was to present the unusual etiology of this form of cuneiform dislocation and Lisfranc joint complex injury.

Common origins of BRCA1 mutations in Canadian breast and ovarian cancer families.

Women who carry mutations in the BRCA1 gene on chromosome 17q have an 85% lifetime risk of breast cancer, and a 60% risk of ovarian cancer. We have identified BRCA1 mutations in 12 of 30 (40%) Canadian families with breast and/or ovarian cancer, including six of the eight families (75%) that contained two cases of early-onset breast cancer and two cases of ovarian cancer. Six frameshift mutations account for all 12 mutant alleles, including nucleotide insertions (two mutations) and deletions (four mutations). Four independent families carried the same 1 basepair (bp) insertion mutation in codon 1755 and four other families shared a 2 bp deletion mutation in codons 22-23. These families were not known to be related, but haplotype analysis suggests that the carriers of each of these mutations have common ancestors.

The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds.

Breast carcinoma is the most common malignancy among women in developed countries. Because family history remains the strongest single predictor of breast cancer risk, attention has focused on the role of highly penetrant, dominantly inherited genes in cancer-prone kindreds (1). BRCA1 was localized to chromosome 17 through analysis of a set of high-risk kindreds (2), and then identified four years later by a positional cloning strategy (3). BRCA2 was mapped to chromosomal 13q at about the same time (4). Just fifteen months later, Wooster et al. (5) reported a partial BRCA2 sequence and six mutations predicted to cause truncation of the BRCA2 protein. While these findings provide strong evidence that the identified gene corresponds to BRCA2, only two thirds of the coding sequence and 8 out of 27 exons were isolated and screened; consequently, several questions remained unanswered regarding the nature of BRCA2 and the frequency of mutations in 13q-linked families. We have now determined the complete coding sequence and exonic structure of BRCA2 (GenBank accession #U43746), and examined its pattern of expression. Here, we provide sequences for a set of PCR primers sufficient to screen the entire coding sequence of BRCA2 using genomic DNA. We also report a mutational analysis of BRCA2 in families selected on the basis of linkage analysis and/or the presence of one or more cases of male breast cancer. Together with the specific mutations described previously, our data provide preliminary insight into the BRCA2 mutation profile.

Antidiabetic drug sitagliptin blocks cyclophosphamide cerebral neurotoxicity by activating Nrf2 and suppressing redox cycle imbalance, inflammatory iNOS/NO/NF-κB response and caspase-3/Bax activation in rats.

Cyclophosphamide (CYP) is a classic DNA-interacting anticancer agent with broad application in chemotherapy. However, CYP cerebral neurotoxicity is a worrisome side effect for clinicians and patients. Strategies to mitigate the underlying oxidative inflammatory cascades and neuroapoptosis induced by CYP are urgently needed. Herein, we have repurposed an antidiabetic drug, sitagliptin (STG), for a possible abrogation of CYP-induced cerebral neurotoxicity in rats. Healthy rats were administered STG (20 mg/kg body weight) for 5 days prior to neurotoxicity induced by CYP (200 mg/kg body weight, ip) on day 5 only, and rats were sacrificed after 24 h post-CYP injection. CYP caused profound increases in the cerebral levels of nitric oxide (NO), acetylcholinesterase (AChE), malondialdehyde (MDA), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), nuclear factor-kappaB (NF-κB), inducible nitric oxide synthase (iNOS), caspase-3 and Bax protein compared to the control. Furthermore, CYP markedly depressed the activities of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD), along with levels of reduced glutathione (GSH) and nuclear factor erythroid 2-related factor2 (Nrf2) compared to the control (p < 0.05). Interestingly, STG pretreatment inhibited the CYP-induced alterations in caspase-3, Bax, pro-inflammatory cytokines, NO, iNOS, AChE, NF-κB, and restored the cerebral antioxidant apparatus, including the Nrf2 and histopathological abrasions. Therefore, these findings show that STG could be repurposed to prevent CYP-induced cerebral toxicity in the brain.

Exogenous cryptococcal endophthalmitis in an immunocompetent patient.

We describe a case of exogenous cryptococcal endophthalmitis without central nervous system (CNS) involvement or systemic infection in an immunocompetent patient. An 82-year-old male with hypertension, hyperlipidemia, type 2 diabetes mellitus, and primary open-angle glaucoma with a history of left eye trabeculectomy presented with 3 months of worsening left eye pain and redness. Vitreous cultures resulted as Cryptococcus, prompting treatment with intravitreal amphotericin and further investigation. Systemic workup was unrevealing for an endogenous source, CNS involvement, or immunocompromising conditions. He was treated with an aggressive regimen of systemic antifungals, leading to subjective improvements in clinical exam and in vision.

"Persistence of Memory" - Multimodal imaging of delayed sympathetic ophthalmia.

Purpose: To describe a case of late post-surgical sympathetic ophthalmia documented with multimodal imaging. Observations: A 74-year-old male presented to the urgent care of the New York Eye and Ear Infirmary with blurry vision and discomfort in his left eye for three weeks. His vision was 20/50, with intraocular pressure of 13 mmHg, and slit lamp examination was significant for conjunctival congestion, 1+ anterior segment cell and flare, and diffuse keratic precipitates. His right eye was no light perception with a condensed hyphema, intraocular lens and inferonasal tube. His medical history included coronary artery bypass, prostate cancer, hyperlipidemia, and hypertension. His ocular history included blunt trauma to the right eye at age 11 with development of a traumatic macular hole and later rhegmatogenous retinal detachment at age 53, repaired with multiple vitreoretinal procedures. He developed glaucoma in the right eye and was treated with a tube shunt and ultimately transscleral cyclophotocoagulation (TSCPC) 7 years later, 13 years prior to his presentation of the left eye. Dilated fundus examination of his left eye revealed diffuse chorioretinal folds in the macula without any discrete chorioretinal lesions. Ultrasound of the right showed serous macular detachments with scleral thickening. Presumptive diagnosis of sympathetic ophthalmia was made and oral corticosteroid therapy was initiated. Subsequent SD-OCT and en-face OCT-A demonstrated Dalen-Fuchs nodules within the macula underlying areas of resolved serous detachment, after 6 weeks of oral steroids and initiation of immunomodulatory therapy (IMT). Conclusions: Sympathetic ophthalmia may rarely present with very delayed onset, and TSCPC is an uncommon inciting event. These patients may develop serous detachment, choroidal folds and inflammatory nodules identifiable on exam and multimodal imaging, which can resolve when treated appropriately. OCT-A may provide utility in monitoring response to immunosuppressive treatment in these patients.

An uncomplicated method for minimally invasive achilles tendon repair.

The Achilles tendon is the largest palpable tendon in the human body, and rupture of this tendon is not an uncommon injury encountered by foot and ankle surgeons. A number of different minimally invasive methods have been described for repair of the ruptured Achilles tendon. In this article, we describe a relatively simple, minimally invasive technique of Achilles tendon repair that does not require special instrumentation, the key requirement being that of a sponge forceps.

Contaminating DNA in human saliva alters the detection of variants from whole genome sequencing.

Cells obtained from human saliva are commonly used as an alternative DNA source when blood is difficult or less convenient to collect. Although DNA extracted from saliva is considered to be of comparable quality to that derived from blood, recent studies have shown that non-human contaminating DNA derived from saliva can confound whole genome sequencing results. The most concerning complication is that non-human reads align to the human reference genome using standard methodology, which can critically affect the resulting variant genotypes identified in a genome. We identified clusters of anomalous variants in saliva DNA derived reads which aligned in an atypical manner. These reads had only short regions of identity to the human reference sequence, flanked by soft clipped sequence. Sequence comparisons of atypically aligning reads from eight human saliva-derived samples to RefSeq genomes revealed the majority to be of bacterial origin (63.46%). To partition the non-human reads during the alignment step, a decoy of the most prevalent bacterial genome sequences was designed and utilised. This reduced the number of atypically aligning reads when trialled on the eight saliva-derived samples by 44% and most importantly prevented the associated anomalous genotype calls. Saliva derived DNA is often contaminated by DNA from other species. This can lead to non-human reads aligning to the human reference genome using current alignment best-practices, impacting variant identification. This problem can be diminished by using a bacterial decoy in the alignment process.

Tesserae on Venus may preserve evidence of fluvial erosion.

Fluvial erosion is usually assumed to be absent on Venus, precluded by a high surface temperature of ~450 °C and supported by extensive uneroded volcanic flows. However, recent global circulation models suggest the possibility of Earth-like climatic conditions on Venus for much of its earlier history, prior to catastrophic runaway greenhouse warming. We observe that the stratigraphically oldest, geologically most complex units, tesserae, exhibit valley patterns morphologically similar to the patterns resulting from fluvial erosion on Earth. Given poor topographic resolution, we use an indirect technique to recognize valleys, based on the pattern of lava flooding of tesserae margins by adjacent plains volcanism. These observed valley patterns are attributed to primary geology, tectonic deformation, followed by fluvial erosion (and lesser wind erosion). This proposed fluvial erosion in tesserae provides support for climate models for a cool, wet climate on early Venus and could be an attractive research theme for future Venus missions.

Bevacizumab (avastin) and ranibizumab (lucentis) for choroidal neovascularization in multifocal choroiditis.

BACKGROUND: Multifocal choroiditis (MFC) is an inflammatory condition, occasionally associated with choroidal neovascularization (CNV). Bevacizumab (Avastin) and ranibizumab (Lucentis) are therapies that target vascular endothelial growth factor. Bevacizumab and ranibizumab have been used successfully to treat CNV in age-related and myopic macular degeneration. PURPOSE: : To describe the treatment of MFC-associated CNV with intravitreal bevacizumab and/or ranibizumab. DESIGN: Retrospective interventional case series. PARTICIPANTS: Six eyes of five patients with MFC-associated CNV were treated with intravitreal bevacizumab and/or ranibizumab. MAIN OUTCOME MEASURES: Visual acuity at 1, 3, and 6 months after the initial injection. RESULTS: Previous therapies (number of eyes treated) included sub-Tenon's corticosteroids (2), intravitreal corticosteroids (1), photodynamic therapy (1), and thermal laser (1). The mean number (range) of antivascular endothelial growth factor injections per eye was 2.3 (1-6). The mean duration (range) of follow-up per patient was 41.5 (25-69) weeks. Five of six eyes improved to 20/30 acuity or better at 6 months. One eye suffered a subfoveal rip of the retinal pigment epithelium with 20/400 acuity. There was a qualitative decrease in clinical and angiographic evidence of CNV. CONCLUSIONS: Bevacizumab and ranibizumab were effective at improving visual acuity over 6 months in a small series of patients with MFC-associated CNV. Tears of the retinal pigment epithelium may occur after intravitreal antivascular endothelial growth factor therapy in MFC-associated CNV.

Are the Current Recommendations for Chloroquine and Hydroxychloroquine Screening Appropriate?

Hydroxychloroquine and quinacrine are frequently used to treat rheumatic diseases. Ocular toxicity, although infrequent, is one of the potential side effects of antimalarial therapies. Current recommendations are unifocal in being developed by only ophthalmologists who do not treat patients for their rheumatic diseases. The data used to create the recommendations are meager and retrospective. Comanagement of patients with rheumatic disease who are exposed to antimalarial therapies requires a greater interaction between ophthalmologists and rheumatologists.

Wheezy swallow: poorly responsive 'asthma'.

We report two children who presented with cough and wheeze, were initially misdiagnosed with asthma and were subsequently demonstrated to have achalasia as the underlying cause of their symptoms. These cases highlight the importance of considering diagnoses other than asthma when there is a suboptimal response to asthma medications, as well as the value of investigations including chest X-ray and pulmonary function tests in establishing the underlying cause.

[Malignancy risk and Wiedemann-Beckwith syndrome: what follow-up to provide?]. / Risque tumoral et syndrome de Wiedemann-Beckwith: quelle surveillance proposer?

Wiedemann-Beckwith syndrome (WBS) is a syndrome of excessive growing with a high predisposition to developing embryologic tumours within the first years of life. This risk is evaluated between 7.5 and 10%; it varies with the mechanisms of mutations involved. These take place in two distinct domains of 11p15, which are under parental printing. Emerging techniques of cytogenetic and molecular biology now have shown correlations between genotypes and phenotypes, and can identify the 30% of WBS who are especially at risk of developing tumours. A specific follow-up, integrating the specificity of developing tumours of each 11p15 mutations involved, is now proposed to patients with WBS.

A Case of Corneal Neovascularization Misdiagnosed as Total Limbal Stem Cell Deficiency.

PURPOSE: To report a case of corneal neovascularization misdiagnosed as total limbal stem cell deficiency (LSCD). METHODS: This is a case report of a 61-year-old woman who has a history of bilateral idiopathic scleritis, keratitis, and uveitis for more than 20 years. She was diagnosed with total LSCD in her left eye based on clinical presentation alone and was confirmed as a candidate for limbal transplantation at several major tertiary eye care centers in the United States. After referral to the Stein Eye Institute, in vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) were performed to clarify the diagnosis. RESULTS: Slit-lamp examination of the left eye revealed 360-degree severe thinning at the limbus and peripheral corneal pannus and neovascularization that spared the central cornea, a smooth epithelium without fluorescein staining at the central cornea, an uneven surface, and pooling of fluorescein at the peripheral cornea accompanied by minimal fluorescein staining of the sectoral peripheral epithelium. IVCM showed that epithelial cells in the central cornea exhibited a corneal phenotype and that the morphology of the epithelium in all limbal regions except the nasal limbus was normal. Epithelial cellular density and thickness were within the normal range. AS-OCT showed severe thinning in the limbus and a normal epithelial layer in the cornea and limbus. Based on the findings of IVCM and AS-OCT, we concluded that the patient had minimal LSCD, and limbal stem cell transplantation was not recommended. CONCLUSIONS: Clinical presentation alone is insufficient to correctly diagnose LSCD in complex cases. Additional diagnostic tests, such as IVCM, are necessary to confirm the diagnosis before any surgical intervention.

Giant sarcoid tumor of the iris and ciliary body.

PURPOSE: To report the occurrence of a giant iridociliary sarcoid tumor. METHODS: The patient was evaluated by medical history, ophthalmoscopic examination (including photography and ultrasonography) as well as systemic, hematologic, and radiographic examinations. Tumor biopsies allowed for cytopathologic, histopathologic, and immunohistochemical analysis. RESULTS: The 39-year-old black male was found to have a right iris and ciliary body tumor. Ultrasonography revealed a 10 x 12-mm base, 5.6-mm height, low internal reflectivity, and vitreous debris. Radiographic imaging revealed mediastinal and bilateral hilar lymphadenopathy. A purified protein derivative (PPD) and a hematologic survey were negative. Pathology evaluations of the surgical specimens revealed features of non-caseating granulomata consistent with sarcoidosis. A combination of topical and systemic steroid therapy was locally curative. CONCLUSIONS: We describe a giant iridociliary sarcoid tumor in a patient with no lacrimal gland enlargement, conjunctival nodules, or skin lesions. A biopsy was required to establish the diagnosis.