Vitreoretinal involvement of lymphoma can be controlled effectively and without serious adverse reactions by intravitreal MTX injections. The treatment protocol described herein has resulted in no intraocular recurrence so far and has had bearable side effects. The accumulating clinical results bring us to propose the consideration of this protocol as a good first-line treatment option for intraocular lymphoma.
Global Retinoblastoma Study Group IMPORTANCE Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale.OBJECTIVES To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. DESIGN, SETTING, AND PARTICIPANTSA total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. MAIN OUTCOMES AND MEASURESAge at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. RESULTSThe cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI,, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI,). CONCLUSIONS AND RELEVANCEThis study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations caused by mutations in at least 50 genes. Using homozygosity mapping in Ashkenazi Jewish (AJ) patients with autosomal-recessive RP (arRP), we identified a shared 1.7 Mb homozygous region on chromosome 1p36.11. Sequence analysis revealed a founder homozygous missense mutation, c.124A>G (p.Lys42Glu), in the dehydrodolichyl diphosphate synthase gene (DHDDS) in 20 AJ patients with RP of 15 unrelated families. The mutation was not identified in an additional set of 109 AJ patients with RP, in 20 AJ patients with other inherited retinal diseases, or in 70 patients with retinal degeneration of other ethnic origins. The mutation was found heterozygously in 1 out of 322 ethnically matched normal control individuals. RT-PCR analysis in 21 human tissues revealed ubiquitous expression of DHDDS. Immunohistochemical analysis of the human retina with anti-DHDDS antibodies revealed intense labeling of the cone and rod photoreceptor inner segments. Clinical manifestations of patients who are homozygous for the c.124A>G mutation were within the spectrum associated with arRP. Most patients had symptoms of night and peripheral vision loss, nondetectable electroretinographic responses, constriction of visual fields, and funduscopic hallmarks of retinal degeneration. DHDDS is a key enzyme in the pathway of dolichol, which plays an important role in N-glycosylation of many glycoproteins, including rhodopsin. Our results support a pivotal role of DHDDS in retinal function and may allow for new therapeutic interventions for RP.
Microphthalmia (mi) is a transcription factor that plays a major role in the regulation of growth and function in mast cells and melanocytes. Association of mi with other proteins is a critical step in the regulation of mi-mediated transcriptional activation. We found protein kinase C-interacting protein 1 (PKCI) specifically associated with mi in yeast two-hybrid screening. Immunoprecipitation of mi from quiescent rat basophilic leukemic cells or mouse melanocytes resulted in the specific co-immunoprecipitation of PKCI. This association was significantly reduced on engagement of the surface Fc⑀RI of mast cells or engagement of the Kit receptor on melanocytes. Hence, cell activation caused disengagement of mi from PKCI. Microphthalmia was previously shown to activate the mouse mast cell protease 6 (mMCP-6) promoter. Cotransfection of mi with PKCI in NIH 3T3 fibroblasts containing an mMCP-6 promoterluciferase reporter demonstrated an up to 94% inhibition of mi-mediated transcriptional activation. PKCI by itself, although localized in the cytosol and nucleus of the cells, has no known physiological function and did not demonstrate transcriptional activity. Its ability to suppres mi transcriptional activity in the transient transfected fibroblast system suggests that it can function in vivo as a negative regulator of mi-induced transcriptional activation. Microphthalmia (mi)1 is a transcription factor of the basic helix-loop-helix leucine zipper (bHLH-Zip) type (1). Homozygous mutations at the mi locus were shown to cause the mouse microphthalmia phenotype (2). This phenotype is now known to contain more than 10 allelic variations (3) and is typified by a decrease in mast cell number, deafness, a defect in osteoclasts, small unpigmented eyes and skin, and a major depletion of inner ear melanocytes (3). In humans, mutation in this gene causes Wardenburg syndrome type II (4).Northern blot of mRNA from different tissues and cell types showed that mi mRNA is present only in a limited number of tissues and cell types, those being heart, uterus, melanocytes, and mast cells (4). It was reported that mi regulates the expression of mouse mast cell protease 6 (mMCP-6) (5) and mouse c-Kit (6, 7) and that mi is involved in the expression of genes involved in pigmentation such as tyrosinase (albino locus), tyrosinase-related protein, and the pink-eyed Pmel 17 (silver) (8). Thus, down-regulation of mi expression plays a significant role in the decreased pigmentation observed in melanoma. We recently investigated the expression of mi in mast cells (9) and found that mi plays a crucial role in cell proliferation.mi binds E-box-type enhancer elements (5), and, like many other transcription factors, mi's activity is probably determined through its interactions with other proteins. It was observed that mi may heterodimerize with the related family members TFEB, TFEC, TFE3 (10 -12), and USF2 (9).In the present work, we have identified other mi-interacting proteins, using a construct containing the mi bHLH-Zip domains as bait in yeast ...
ObjectiveTo present an established practice protocol for safe and effective hospital-setting ophthalmic practice during the coronavirus disease 2019 (COVID-19) pandemic.Methods and AnalysisLiterature was reviewed to identify articles relevant to COVID-19 pandemic and ophthalmology. The following keywords were used: COVID-19, SARS-CoV-2 and telemedicine, combined with eye, ophthalmology, conjunctivitis and tears. Data were extracted from the identified manuscripts and discussed among subspecialists to obtain consensus evidence-based practice.ResultsA protocol for ophthalmic practice in the era of COVID-19 pandemic was established. The protocol covered patient screening, clinic flow, required personal protective equipment and modifications of ophthalmic equipment for improved safety.ConclusionImportant literature emerged with respect to the practice of ophthalmology in the era of COVID-19. An evidence-based ophthalmic practice protocol was established and should be modified in the future to accommodate new insights on the COVID-19 pandemic.
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