A Rare Complication Causing Another Rare Complication: Corneal Dellen with Infiltration Secondary to Subconjunctival Silicon Oil.

The usage of silicon oil (SO) in vitreoretinal surgery is associated with potential complications. One such complication is the extravasation of SO into the subconjunctival space through open sclerotomies. Subconjunctival SO (SCSO) can cause irregularities in the ocular surface which predisposes to complications like corneal dellen. This corneal dellen can get infected in rare situations. SCSO needs to be removed to stabilize the ocular surface. We present a case of corneal dellen with infiltration which developed as a consequence of SCSO and its management.

Taming the polar bear: Ten tips to manage posterior polar cataract.

Background: Posterior polar cataracts are challenging even for skilled cataract surgeons due to the high risk of posterior capsule rupture and vitreous loss during cataract surgery; hence, it is important to know how to manage such cases. Purpose: In this video, we describe the necessary precautions and steps to be taken to prevent and manage complications in phacoemulsification cataract surgery for posterior polar cataracts. Synopsis: The video contains ten tips to follow to avoid complications while performing phacoemulsification cataract surgery in patients with posterior polar cataracts and includes preoperative identification on slit-lamp examination, size of capsulorhexis, avoidance of hydrodissection, technique of nucleus management, viscoelastic injection to keep the anterior chamber formed, epinucleus and cortical matter removal, posterior capsular rupture management, anterior vitrectomy, and intraocular lens (IOL) implantation in eyes with posterior capsular rupture. Highlights: The video highlights ten different steps to be followed in the surgical management of patients with posterior polar cataract which, if followed meticulously, can give excellent outcomes in these patients. Conclusion: Posterior polar cataracts can be managed with phacoemulsification, with good visual outcomes if these precautions are followed. Video link: https://youtu.be/TeoLckE83xM. Additional information: Won Best Educational Video in a contest by phacotraining.org.

Management of acute hydrops with pre-Descemet's deep anterior lamellar keratoplasty.

This case report describes a 23-year-old female patient who had bilateral keratoconus and a history of right eye penetrating keratoplasty who presented with acute hydrops in the left eye which did not respond to conservative management. Pre-Descemet's deep anterior lamellar keratoplasty was performed in the acute stage for management of the impending perforation with good visual outcomes.

Micropulse trans-scleral diode laser cyclophotocoagulation in refractory glaucoma: an initial experience in Indian eyes.

PURPOSE: To evaluate the efficacy and safety of micro-pulse trans-scleral diode laser cyclophotocoagulation (MP-TSCPC) in Indian eyes with refractory glaucoma. METHODS: A prospective interventional short-term study was carried out with relatively small sample size of 55 eyes with refractory glaucoma. All eyes had visual acuity (VA) and intraocular pressure (IOP) measurements at baseline, 1 week (1w), 1 month (1 m) and 3 months (3 m). A single surgeon treated all eyes with recommended MP-TSCPC treatment settings. Surgical success was defined as achieving an IOP between 8-21 mmHg or achieving > 20% IOP reduction. RESULTS: The age of participants was 56.98 ± 15.74 years. Our study had more number of males. VA (in logMAR) at baseline was 1.38 ± 0.99. VA was 1.43 ± 0.93 at 1w, 1.47 ± 0.94 at 1 m and 1.47 ± 0.96 at 3 m (p > 0.05 for all). IOP (in mmHg) at baseline was 30.38 ± 10.70. IOP was 15.72 ± 6.85 at 1w, 16.98 ± 8.72 at 1 m and 17.60 ± 8.40 at 3 m (p < 0.001 for all). At 3 m, 49 (89.1%) eyes had surgical success. Surgical success was lesser in primary open angle glaucoma (p = 0.03). IOP at baseline showed significant correlation with percentage reduction in IOP at each review (p < 0.05). Use of glaucoma medication reduced from 2.94 ± 0.98 to 2.01 ± 1.16 at 3 m (p < 0.001). At 3 m, hypotony was noted in 4 (7.3%) eyes and reduction in visual acuity was seen in 15 (27.3%) eyes. CONCLUSION: Initial experience in Indian eyes has shown that MP-TSCPC is safe and effective for refractory glaucoma. Patients can expect significant IOP lowering along with reduction in number of topical medications required for control of IOP.

Towards label-free 3D segmentation of optical coherence tomography images of the optic nerve head using deep learning.

Recently proposed deep learning (DL) algorithms for the segmentation of optical coherence tomography (OCT) images to quantify the morphological changes to the optic nerve head (ONH) tissues during glaucoma have limited clinical adoption due to their device specific nature and the difficulty in preparing manual segmentations (training data). We propose a DL-based 3D segmentation framework that is easily translatable across OCT devices in a label-free manner (i.e. without the need to manually re-segment data for each device). Specifically, we developed 2 sets of DL networks: the 'enhancer' (enhance OCT image quality and harmonize image characteristics from 3 devices) and the 'ONH-Net' (3D segmentation of 6 ONH tissues). We found that only when the 'enhancer' was used to preprocess the OCT images, the 'ONH-Net' trained on any of the 3 devices successfully segmented ONH tissues from the other two unseen devices with high performance (Dice coefficients > 0.92). We demonstrate that is possible to automatically segment OCT images from new devices without ever needing manual segmentation data from them.

Glued intraocular lens implantation for eyes with inadequate capsular support: Analysis of the postoperative visual outcome.

AIM: The aim of this study is to analyze the postoperative visual outcomes of fibrin glue-assisted, suture-less posterior chamber (PC) intraocular lens (IOL) implantation technique in eyes with inadequate capsule support at a tertiary eye care hospital in South India. SETTING AND DESIGN: This is a retrospective, nonrandomized case series. PATIENTS AND METHODS: This study analyzes 94 eyes which underwent PC-IOL implantation by fibrin glue-assisted, suture-less technique. All patients who had IOL implants by the fibrin glue-assisted PC-IOL technique from August 2009 to January 2014 were included in the study. Intra- and post-operative complications were analyzed. The postoperative best spectacle-corrected visual acuity (BSCVA) was evaluated and recorded at the end of 6 months. STATISTICAL ANALYSIS: The data were analyzed using SPSS version 16.1 (SPSS Inc., Chicago, Illinois, USA) using two sample paired t-test and independent t-test. RESULTS: A total of 94 eyes of 92 patients that underwent glued IOL implantation over a period of 5 years were analyzed. Out of 94 eyes, 77 eyes (84.6%) maintained or improved on their preoperative BSCVA (P = 0.012). CONCLUSION: We conclude that glued IOL implantation is a feasible option in rehabilitating patients with aphakia without adequate capsular support.

Proteomic analysis of human osteoarthritis synovial fluid.

BACKGROUND: Osteoarthritis is a chronic musculoskeletal disorder characterized mainly by progressive degradation of the hyaline cartilage. Patients with osteoarthritis often postpone seeking medical help, which results in the diagnosis being made at an advanced stage of cartilage destruction. Sustained efforts are needed to identify specific markers that might help in early diagnosis, monitoring disease progression and in improving therapeutic outcomes. We employed a multipronged proteomic approach, which included multiple fractionation strategies followed by high resolution mass spectrometry analysis to explore the proteome of synovial fluid obtained from osteoarthritis patients. In addition to the total proteome, we also enriched glycoproteins from synovial fluid using lectin affinity chromatography. RESULTS: We identified 677 proteins from synovial fluid of patients with osteoarthritis of which 545 proteins have not been previously reported. These novel proteins included ADAM-like decysin 1 (ADAMDEC1), alanyl (membrane) aminopeptidase (ANPEP), CD84, fibulin 1 (FBLN1), matrix remodelling associated 5 (MXRA5), secreted phosphoprotein 2 (SPP2) and spondin 2 (SPON2). We identified 300 proteins using lectin affinity chromatography, including the glycoproteins afamin (AFM), attractin (ATRN), fibrillin 1 (FBN1), transferrin (TF), tissue inhibitor of metalloproteinase 1 (TIMP1) and vasorin (VSN). Gene ontology analysis confirmed that a majority of the identified proteins were extracellular and are mostly involved in cell communication and signaling. We also confirmed the expression of ANPEP, dickkopf WNT signaling pathway inhibitor 3 (DKK3) and osteoglycin (OGN) by multiple reaction monitoring (MRM) analysis of osteoarthritis synovial fluid samples. CONCLUSIONS: We present an in-depth analysis of the synovial fluid proteome from patients with osteoarthritis. We believe that the catalog of proteins generated in this study will further enhance our knowledge regarding the pathophysiology of osteoarthritis and should assist in identifying better biomarkers for early diagnosis.

Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients.

BACKGROUND: Rheumatoid arthritis and osteoarthritis are two common musculoskeletal disorders that affect the joints. Despite high prevalence rates, etiological factors involved in these disorders remain largely unknown. Dissecting the molecular aspects of these disorders will significantly contribute to improving their diagnosis and clinical management. In order to identify proteins that are differentially expressed between these two conditions, a quantitative proteomic profiling of synovial fluid obtained from rheumatoid arthritis and osteoarthritis patients was carried out by using iTRAQ labeling followed by high resolution mass spectrometry analysis. RESULTS: We have identified 575 proteins out of which 135 proteins were found to be differentially expressed by ≥3-fold in the synovial fluid of rheumatoid arthritis and osteoarthritis patients. Proteins not previously reported to be associated with rheumatoid arthritis including, coronin-1A (CORO1A), fibrinogen like-2 (FGL2), and macrophage capping protein (CAPG) were found to be upregulated in rheumatoid arthritis. Proteins such as CD5 molecule-like protein (CD5L), soluble scavenger receptor cysteine-rich domain-containing protein (SSC5D), and TTK protein kinase (TTK) were found to be upregulated in the synovial fluid of osteoarthritis patients. We confirmed the upregulation of CAPG in rheumatoid arthritis synovial fluid by multiple reaction monitoring assay as well as by Western blot. Pathway analysis of differentially expressed proteins revealed a significant enrichment of genes involved in glycolytic pathway in rheumatoid arthritis. CONCLUSIONS: We report here the largest identification of proteins from the synovial fluid of rheumatoid arthritis and osteoarthritis patients using a quantitative proteomics approach. The novel proteins identified from our study needs to be explored further for their role in the disease pathogenesis of rheumatoid arthritis and osteoarthritis.Sartaj Ahmad and Raja Sekhar Nirujogi contributed equally to this article.

Proteomic profiling and functional characterization of early and late shoulder osteoarthritis.

INTRODUCTION: The development of effective treatments for osteoarthritis (OA) has been hampered by a poor understanding of OA at the cellular and molecular levels. Emerging as a disease of the 'whole joint', the importance of the biochemical contribution of various tissues, including synovium, bone and articular cartilage, has become increasingly significant. Bathing the entire joint structure, the proteomic analysis of synovial fluid (SF) from osteoarthritic shoulders offers a valuable 'snapshot' of the biologic environment throughout disease progression. The purpose of this study was to identify differentially expressed proteins in early and late shoulder osteoarthritic SF in comparison to healthy SF. METHODS: A quantitative 18O labeling proteomic approach was employed to identify the dysregulated SF proteins in early (n = 5) and late (n = 4) OA patients compared to control individuals (n = 5). In addition, ELISA was used to quantify six pro-inflammatory and two anti-inflammatory cytokines. RESULTS: Key results include a greater relative abundance of proteins related to the complement system and the extracellular matrix in SF from both early and late OA. Pathway analyses suggests dysregulation of the acute phase response, liver x receptor/retinoid x receptor (LXR/RXR), complement system and coagulation pathways in both early and late OA. The network related to lipid metabolism was down-regulated in both early and late OA. Inflammatory cytokines including interleukin (IL) 6, IL 8 and IL 18 were up-regulated in early and late OA. CONCLUSIONS: The results suggest a dysregulation of wound repair pathways in shoulder OA contributing to the presence of a 'chronic wound' that progresses irreversibly from early to later stages of OA. Protease inhibitors were downregulated in late OA suggesting uncontrolled proteolytic activity occurring in late OA. These results contribute to the theory that protease inhibitors represent promising therapeutic agents which could limit proteolytic activity that ultimately leads to cartilage destruction.

Characterizing the normal proteome of human ciliary body.

BACKGROUND: The ciliary body is the circumferential muscular tissue located just behind the iris in the anterior chamber of the eye. It plays a pivotal role in the production of aqueous humor, maintenance of the lens zonules and accommodation by changing the shape of the crystalline lens. The ciliary body is the major target of drugs against glaucoma as its inhibition leads to a drop in intraocular pressure. A molecular study of the ciliary body could provide a better understanding about the pathophysiological processes that occur in glaucoma. Thus far, no large-scale proteomic investigation has been reported for the human ciliary body. RESULTS: In this study, we have carried out an in-depth LC-MS/MS-based proteomic analysis of normal human ciliary body and have identified 2,815 proteins. We identified a number of proteins that were previously not described in the ciliary body including importin 5 (IPO5), atlastin-2 (ATL2), B-cell receptor associated protein 29 (BCAP29), basigin (BSG), calpain-1 (CAPN1), copine 6 (CPNE6), fibulin 1 (FBLN1) and galectin 1 (LGALS1). We compared the plasma proteome with the ciliary body proteome and found that the large majority of proteins in the ciliary body were also detectable in the plasma while 896 proteins were unique to the ciliary body. We also classified proteins using pathway enrichment analysis and found most of proteins associated with ubiquitin pathway, EIF2 signaling, glycolysis and gluconeogenesis. CONCLUSIONS: More than 95% of the identified proteins have not been previously described in the ciliary body proteome. This is the largest catalogue of proteins reported thus far in the ciliary body that should provide new insights into our understanding of the factors involved in maintaining the secretion of aqueous humor. The identification of these proteins will aid in understanding various eye diseases of the anterior segment such as glaucoma and presbyopia.

Overexpression of ribosome binding protein 1 (RRBP1) in breast cancer.

The molecular events that lead to malignant transformation and subsequent metastasis of breast carcinoma include alterations in the cells at genome, transcriptome and proteome levels. In this study, we used publicly available gene expression databases to identify those candidate genes which are upregulated at the mRNA level in breast cancers but have not been systematically validated at the protein level. Based on an extensive literature search, we identified ribosome binding protein 1 (RRBP1) as a candidate that is upregulated at the mRNA level in five different studies but its protein expression had not been investigated. Immunohistochemical labeling of breast cancer tissue microarrays was carried out to determine the expression of RRBP1 in a large panel of breast cancers. We found that RRBP1 was overexpressed in 84% (177/219) of breast carcinoma cases tested. The subcellular localization of RRBP1 was mainly observed to be in the cytoplasm with intense staining in the perinuclear region. Our findings suggest that RRBP1 is an interesting molecule that can be further studied for its potential to serve as a breast cancer biomarker. This study also demonstrates how the integration of biological data from available resources in conjunction with systematic evaluation approaches can be successfully applied to clinical proteomics.

Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus.

PURPOSE: To investigate the expression of proteases, proteolytic activity and cytokines in the tear film of people with keratoconus. METHODS: Basal tears from people with keratoconus, from individuals who had undergone corneal collagen cross-linking for the treatment of keratoconus, and from normal controls were collected using a capillary tube. Corneal curvature of each subject was mapped. The total protein in tears was estimated. Levels and activity of proteases in the tears were analysed using specific antibody arrays and activity assays. RESULTS: The total tear protein level was significantly reduced in keratoconus (4.1 ± 0.9 mg/ml) compared with normals (6.7 ± 1.4 mg/ml) (p < 0.0001) or subjects who had undergone corneal collagen cross-linking (5.7 ± 2.3 mg/ml) (p < 0.005). Significantly (p < 0.05) increased tear expression of matrix metalloproteinases (MMP) -1, -3, -7, -13, interleukins (IL) -4, -5, -6, -8 and tumour necrosis factor (TNF) -α, -ß were evident in keratoconus. Tear IL-6 was the only cytokine significantly (p < 0.05) increased in tears of keratoconus subjects compared with the collagen cross-linked group. No significant difference in tear proteases were observed between the normal and the cross-linked groups, although the expression of TNF-α was significantly (p < 0.05) increased in the cross-linked group compared with the controls. Elevated gelatinolytic (87.5 ± 33.6 versus 45.8 ± 24.6 FIU, p < 0.0001) and collagenolytic (6.1 ± 3.2 versus 3.6 ± 2.0 FIU, p < 0.05) activities were observed in tears from keratoconus compared with normal subjects. The activity of tear gelatinases (69.6 ± 22.2 FIU) and collagenases (5.7 ± 3.3 FIU) in the collagen cross-linked group was not significantly different compared with either keratoconus or normals. CONCLUSION: Tears of people with keratoconus had 1.9 times higher levels of proteolytic activity and over expression of several MMPs and cytokines compared with tears from controls. Further investigations are required to study the possible implications of these changes and whether they can be used to monitor disease progression or determine the success of corneal collagen cross-linking.

The RIKEN integrated database of mammals.

The RIKEN integrated database of mammals (http://scinets.org/db/mammal) is the official undertaking to integrate its mammalian databases produced from multiple large-scale programs that have been promoted by the institute. The database integrates not only RIKEN's original databases, such as FANTOM, the ENU mutagenesis program, the RIKEN Cerebellar Development Transcriptome Database and the Bioresource Database, but also imported data from public databases, such as Ensembl, MGI and biomedical ontologies. Our integrated database has been implemented on the infrastructure of publication medium for databases, termed SciNetS/SciNeS, or the Scientists' Networking System, where the data and metadata are structured as a semantic web and are downloadable in various standardized formats. The top-level ontology-based implementation of mammal-related data directly integrates the representative knowledge and individual data records in existing databases to ensure advanced cross-database searches and reduced unevenness of the data management operations. Through the development of this database, we propose a novel methodology for the development of standardized comprehensive management of heterogeneous data sets in multiple databases to improve the sustainability, accessibility, utility and publicity of the data of biomedical information.