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Featured researches published by Hind Alkatan.


Archives of Ophthalmology | 2009

Epithelial lacrimal gland tumors: pathologic classification and current understanding.

Ezekiel Weis; Jack Rootman; Thomas J. Joly; Kenneth W. Berean; Hind Alkatan; Sylvia Pasternak; Giulio Bonavolontà; Diego Strianese; Peerooz Saeed; Kenneth A. Feldman; Sumalee Vangveeravong; Jocelyne S. Lapointe; Valerie A. White

OBJECTIVE To apply the updated epithelial salivary gland classification scheme to a large cohort of lacrimal gland tumors so as to provide an updated lacrimal gland tumor classification scheme. METHODS A retrospective multicenter cohort study of 118 cases of epithelial neoplasia was undertaken. Main outcome measures included pathologic analysis, subtyping, and survival. RESULTS Of 118 cases, 17 (14%) were reclassified using the proposed expanded classification scheme based on the current World Health Organization classification of salivary gland tumors. The most frequent neoplasms were pleomorphic adenoma and adenoid cystic carcinoma, of which we highlight more unusual histologic features. Three tumors were found to be unclassifiable with the updated scheme, with 2 having histologically malignant features. Deficiencies and variations in pathologic assessment were noted. Variation in the histologic findings of pleomorphic adenoma and assessment of the extent of invasion of carcinoma ex pleomorphic adenoma were highlighted. CONCLUSIONS The use of the more histologically diverse classification of salivary gland tumors can be successfully applied to the epithelial lacrimal gland neoplasms. This expanded classification system led to reclassifying 14% of cases. Currently, there are no consistent pathologic standards for processing and evaluating these lesions.


Ophthalmology | 2012

Congenital Ectropion Uvea and Mechanisms of Glaucoma in Neurofibromatosis Type 1:: New Insights

Deepak P. Edward; Jose Morales; Rachida Bouhenni; Jayaprakash Patil; Priya R. Edward; Thomas J. Cummings; Imtiaz A. Chaudhry; Hind Alkatan

OBJECTIVE To describe the clinicopathologic features of congenital ectropion uvea associated with glaucoma in neurofibromatosis-1 (NF-1). DESIGN Retrospective case series. PARTICIPANTS AND CONTROLS Five cases of NF-1 associated with glaucoma, from which enucleated eyes were available, and 2 eye bank eyes used as controls. METHODS The clinical features and courses of these patients were reviewed. Formalin-fixed, paraffin-embedded eyes were examined by light and electron microscopy. Immunohistochemistry using antineurofibromin, anti-glial fibrillary acidic protein, and antivimentin was performed in 3 patients. Gene expression of the mitogen-activated protein kinase (MAPK) signaling pathway was examined in corneal endothelial cells in 1 patient. MAIN OUTCOME MEASURES Cause of glaucoma in patients with ectropion uvea and NF-1. RESULTS The age of patients at the time of glaucoma diagnosis ranged from birth to 13 years. Four of the 5 patients had megalocornea and buphthalmos at presentation. Ectropion uvea was noted clinically in 2 patients, but was demonstrated histopathologically in all 5 patients. On histopathologic examination, all patients had varying degrees of angle closure secondary to endothelialization of the anterior chamber angle. Uveal neurofibromas were noted in all patients; anteriorly displaced ciliary processes were noted in 4 of 5 patients who demonstrated ciliary body involvement with neurofibromas. Absence of Schlemms canal was observed. The endothelial cells lining the closed angle demonstrated positive stain results with the vimentin antibody. Positive antineurofibromin immunolabeling was detected in normal control corneal endothelium, but was absent in corneal endothelium in patients with endothelialization of the angle. Upregulation of genes from the MAPK signaling pathway was demonstrated in the corneal endothelial cells isolated from the NF-1 eyes. CONCLUSIONS Ectropion uvea in NF-1 glaucoma is secondary to endothelialization of the anterior chamber angle and is associated commonly with severe pediatric glaucoma in NF-1 patients. The endothelial cell proliferation may be related to overexpression of the Ras (Rat sarcoma)-MAPK genes in these eyes.


Canadian Journal of Ophthalmology-journal Canadien D Ophtalmologie | 2011

Medulloepithelioma of the ciliary body: the delay in diagnosis and frequent initial mismanagement.

Hind Alkatan; Mohammad Al-Amry; Hailah Al-Hussain; Hassan Al-Dhibi; Saleh Al-Mesfer

OBJECTIVE Medulloepithelioma is a rare intraocular embryonal neuroepithelial tumour. The study aims at identifying the causes for the delay in diagnosis and treatment. DESIGN A retrospective study of all cases with histopathologic diagnosis of medulloepithelioma over a period of 25 years. PARTICIPANTS Six patients with intraocular tumour in 6 eyes. METHODS A data collection sheet is used for clinical and radiologic information based on charts review. The histologic sections are reviewed by a single pathologist. RESULTS All cases presented initially in childhood with equal sex distribution. There was a delay of up to 5 years until final diagnosis and management. The most common clinical findings were high intraocular pressure and/or cataract in 4 cases, visible mass/uveitis/iris neovascularization and buphthalmos each presenting in 50% of the patients. The diagnosis was established clinically in 2 cased and by ultrasound in 4 cases. The tumour was mostly malignant (4/6) and 2 cases were classified as teratoid (1 benign and 1 malignant). All patients were successfully treated by enucleation with a follow-up period up to 18 years. CONCLUSIONS Medulloepithelioma is a rare intraocular tumour often misdiagnosed and treated as glaucoma or uveitis. Ultrasonography is a useful additional tool for diagnosis. Enucleation seems to be an appropriate method of treatment specially when diagnosis is delayed and malignancy is suspected. Ophthalmologists need to be more familiar with this tumour to allow early clinical recognition and diagnosis.


Investigative Ophthalmology & Visual Science | 2012

Pro-Inflammatory Cytokines and Gelatinases in Climatic Droplet Keratopathy

Juha M. Holopainen; Alexandra Robciuc; Thamara A. Cafaro; Maria Fernanda Suarez; Yrj̈o T. Konttinen; Hind Alkatan; Khalid F. Tabbara; Taina Tervahartiala; Timo Sorsa; Julio A. Urrets-Zavalia; Horacio M. Serra

PURPOSE Climatic droplet keratopathy (CDK) is a degenerative disease of the cornea with possible involvement from matrix metalloproteinases (MMPs). Therefore, the authors investigated histologic distribution, levels, and molecular forms of MMP-2 and MMP-9, as well as tear fluid levels of MMPs and cytokines in CDK patients. They additionally examined UV-B-irradiation effect on production of gelatinases and cytokines by human corneal epithelial (HCE) cell culture model. METHODS Tears were collected from 20 unrelated individuals (10 with CDK and 10 controls). CDK affected corneas were haematoxylin-eosin stained and the presence and distribution of MMP-2 and MMP-9 was examined using immunohistochemistry. Gelatinases and cytokine secretion was measured in tears and supernatants from UV-B-exposed HCEs by immunoblotting, gelatin zymography, and protein array, respectively. RESULTS MMP-2 and MMP-9 values were significantly higher in tears collected from CDK patients than healthy controls and were accompanied by pro-inflammatory cytokine secretion. Immunohistochemistry showed that MMP-2 was expressed at the basement membrane zone in both control and affected corneas, but also marked the edges of the granular CDK deposits; MMP-9 expression was restrained to basal layers of the epithelium and was markedly induced in CDK corneas. In HCE cells, UV-B increased gelatinase secretion, with a striking effect on MMP-9, and was preceded by pro-inflammatory cytokine release. CONCLUSIONS The authors demonstrate that the corneal epithelium could participate in CDK development as a source of cytokines and gelatinases. Additionally, in HCE cells, UV-B- modulated cytokine and subsequent MMP secretion. Local inhibition of cytokine secretion and gelatinases may prevent CDK progression.


PLOS ONE | 2015

MicroRNA Profiling in Intraocular Medulloepitheliomas

Deepak P. Edward; Hind Alkatan; Qundeel Rafiq; Charles G. Eberhart; Saleh Al Mesfer; N. G. Ghazi; Leen Al Safieh; Altaf A. Kondkar; Khaled K. Abu Amero

Purpose To study the differential expression of microRNA (miRNA) profiles between intraocular medulloepithelioma (ME) and normal control tissue (CT). Material and Methods Total RNA was extracted from formalin fixed paraffin embedded (FFPE) intraocular ME (n=7) and from age matched ciliary body controls (n=8). The clinical history and phenotype was recorded. MiRNA profiles were determined using the Affymetrix GeneChip miRNA Arrays analyzed using expression console 1.3 software. Validation of significantly dysregulated miRNA was confimed by quantitaive real-time PCR. The web-based DNA Intelligent Analysis (DIANA)-miRPath v2.0 was used to perform enrichment analysis of differentially expressed (DE) miRNA gene targets in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Results The pathologic evaluation revealed one benign (benign non-teratoid, n=1) and six malignant tumors (malignant teratoid, n=2; malignant non-teratoid, n = 4). A total of 88 miRNAs were upregulated and 43 miRNAs were downregulated significantly (P<0.05) in the tumor specimens. Many of these significantly dysregulated miRNAs were known to play various roles in carcinogenesis and tumor behavior. RT-PCR validated three significantly upregulated miRNAs and three significantly downregulated miRNAs namely miR-217, miR-216a, miR-216b, miR-146a, miR-509-3p and miR-211. Many DE miRNAs that were significant in ME tumors showed dysregulation in retinoblastoma, glioblastoma, and precursor, normal and reactive human cartilage. Enriched pathway analysis suggested a significant association of upregulated miRNAs with 15 pathways involved in prion disease and several types of cancer. The pathways involving significantly downregulated miRNAs included the toll-like receptor (TLR) (p<4.36E-16) and Nuclear Factor kappa B (NF-κB) signaling pathways (p<9.00E-06). Conclusions We report significantly dysregulated miRNAs in intraocular ME tumors, which exhibited abnormal profiles in other cancers as well such as retinoblastoma and glioblastoma. Pathway analysis of all dysregulated miRNAs shared commonalities with other cancer pathways.


Experimental and Molecular Pathology | 2015

Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling.

James T. Rosenbaum; Dongseok Choi; David J. Wilson; Hans E. Grossniklaus; Christina A. Harrington; Cailin H. Sibley; Roger A. Dailey; John D. Ng; Eric A. Steele; Craig N. Czyz; Jill A. Foster; David T. Tse; Chris Alabiad; Sander R. Dubovy; Prashant K. Parekh; Gerald J. Harris; Michael Kazim; Payal J. Patel; Valerie A. White; Peter J. Dolman; Bobby S. Korn; Don O. Kikkawa; Deepak P. Edward; Hind Alkatan; Hailah Al-Hussain; R. Patrick Yeatts; Dinesh Selva; Patrick Stauffer; Stephen R. Planck

Biopsies and ANCA testing for limited forms of granulomatosis with polyangiitis (GPA) are frequently non-diagnostic. We characterized gene expression in GPA and other causes of orbital inflammation. We tested the hypothesis that a sub-set of patients with non-specific orbital inflammation (NSOI, also known as pseudotumor) mimics a limited form of GPA. Formalin-fixed, paraffin-embedded orbital biopsies were obtained from controls (n=20) and patients with GPA (n=6), NSOI (n=25), sarcoidosis (n=7), or thyroid eye disease (TED) (n=20) and were divided into discovery and validation sets. Transcripts in the tissues were quantified using Affymetrix U133 Plus 2.0 microarrays. Distinct gene expression profiles for controls and subjects with GPA, TED, or sarcoidosis were evident by principal coordinate analyses. Compared with healthy controls, 285 probe sets had elevated signals in subjects with GPA and 1472 were decreased (>1.5-fold difference, false discovery rate adjusted p<0.05). The immunoglobulin family of genes had the most dramatic increase in expression. Although gene expression in GPA could be readily distinguished from gene expression in TED, sarcoidosis, or controls, a comparison of gene expression in GPA versus NSOI found no statistically significant differences. Thus, forms of orbital inflammation can be distinguished based on gene expression. NSOI/pseudotumor is heterogeneous but often may be an unrecognized, localized form of GPA.


Middle East African Journal of Ophthalmology | 2014

Pigmented hypopyon in association with Listeria monocytogenes endopthalmitis: An interesting case report following refractive surgery procedure with literature review

Hind Alkatan; Hassan Al-Dhibi; Deepak P. Edward; Ali A. Al-Rajhi

Purpose: Listeria monocytogenes is an aerobic, motile, gram positive bacillus recognized as an intercellular pathogen in human where it most frequently affects neonates, pregnant women, elderly patients, and immunosuppressed individuals as well as healthy persons. Ocular listeriosis is rare, most frequently in the form of conjunctivitis, but has been also shown to cause rarely endophthalmitis with pigmented hypopyon and elevated intraocular pressure such as in our case. Materials and Methods: We are reporting one immunocompetent patient presenting with dark hypopyon following laser refractive procedure. His clinical findings, investigations, and further management are all described with relevant literature review of similar cases. Results: Diagnosis of ocular listeriosis was confirmed by positive culture of anterior chamber (AC) aspirate with identification of the above organism. His visual outcome was satisfactory with good preserved vision. Conclusion: We believe that his ocular infection was exogenous and that ophthalmologists should be aware of the causative organisms of colored hypopyon to avoid delayed diagnosis.


Microscopy Research and Technique | 2014

Ultrastructural and three‐dimensional study of post‐LASIK ectasia cornea

Saeed Akhtar; Hind Alkatan; O Kirat; Turki Almubrad

INTRODUCTION: Post‐laser in situ keratomileusis (LASIK) corneal ectasia is a serious late postoperative complication. Here, we report the ultrastructural features of the post‐LASIK cornea of two patients. METHODS: Two normal corneas (age 24 and 37 years old) and two post‐LASIK ectaic corneas from two patients (A and B) were studied. The “patient A” (age 27 years) underwent penetrating keratoplasty and “patient B” (age 31 years) underwent deep‐anterior lamellar keratoplasty. The excised corneas were processed for light and electron microscopy. A total of 120 images for three‐dimensional (3D) reconstruction were taken by using the software “Recorder” and using a bottom mounted camera “Quemesa” attached to a JOEL 1400 transmission electron microscope. The 3D images were constructed using “Visual Kai” software. RESULTS: In the post‐LASIK cornea, the hemidesmosomes, the basement membrane, and Bowman”s layer were abnormal. The stromal lamellae were thin and disorganized. The collagen fibrils (CFs) diameter and interfibrillar spacing had decreased. Aggregated microfibrils were present in the Bowmans layer and all parts of the stroma. A large number of microfilaments were present at the detachment end of the flap and residual stroma. The 3D images showed the presence of collagen microfibrils and proteoglycans (PGs) within the CF of the normal and post‐LASIK cornea. The collagen microfibrils and PGs within the CFs had degenerated in the post‐LASIK cornea. CONCLUSION: Collagen microfibrils and PGs within the CFs were degenerated, leading to the degeneration of CFs, followed by the disorganization of lamellae in post‐LASIK cornea. The CFs diameter and interfibrillar spacing decreased. Microsc. Res. Tech. 77:91–98, 2014.


International Ophthalmology | 2011

Endogenous endophthalmitis associated with liver abscess caused by Klebsiella pneumoniae.

Ammar M. Al-Mahmood; Ghada Y. Al-Binali; Hind Alkatan; Emad B. Abboud; Ahmed M. Abu El-Asrar

To report two unusual cases of endogenous endophthalmitis associated with liver abscess caused by Klebsiella pneumoniae. Retrospective, interventional case series. Two patients, known to have type II diabetes mellitus, presented with sudden visual loss following several days of abdominal pain. Examinations and investigations revealed endogenous endophthalmitis caused by K. pneumoniae. Despite treatment in the form of intravitreal injection of antibiotics in the first patient and pars plana vitrectomy coupled with intravitreal injection of antibiotics in the second patient the final visual outcome was poor in both cases. The possibility of K. pneumoniae endogenous endophthalmitis should be suspected in diabetic patients presenting with intraocular inflammation.


JAMA Ophthalmology | 2015

Parallel Gene Expression Changes in Sarcoidosis Involving the Lacrimal Gland, Orbital Tissue, or Blood

James T. Rosenbaum; Dongseok Choi; David J. Wilson; Hans E. Grossniklaus; Christina A. Harrington; Cailin H. Sibley; Roger A. Dailey; John D. Ng; Eric A. Steele; Craig N. Czyz; Jill A. Foster; David T. Tse; Chris Alabiad; Sander R. Dubovy; Prashant K. Parekh; Gerald J. Harris; Michael Kazim; Payal J. Patel; Valerie A. White; Peter J. Dolman; Bobby S. Korn; Don O. Kikkawa; Deepak P. Edward; Hind Alkatan; Hailah Al-Hussain; R. Patrick Yeatts; Dinesh Selva; Patrick Stauffer; Stephen R. Planck

IMPORTANCE Sarcoidosis is a major cause of ocular or periocular inflammation. The pathogenesis of sarcoidosis is incompletely understood and diagnosis often requires a biopsy. OBJECTIVE To determine how gene expression in either orbital adipose tissue or the lacrimal gland affected by sarcoidosis compares with gene expression in other causes of orbital disease and how gene expression in tissue affected by sarcoidosis compares with gene expression in peripheral blood samples obtained from patients with sarcoidosis. DESIGN, SETTING, AND PARTICIPANTS In a multicenter, international, observational study, gene expression profiling of formalin-fixed biopsy specimens, using GeneChipp U133 Plus 2 microarrays (Affymetrix), was conducted between October 2012 and January 2014 on tissues biopsied from January 2000 through June 2013. Participants included 12 patients with orbital sarcoidosis (7 in adipose tissue; 5 affecting the lacrimal gland) as well as comparable tissue from 6 healthy individuals serving as controls or patients with thyroid eye disease, nonspecific orbital inflammation, or granulomatosis with polyangiitis. In addition, results were compared with gene expression in peripheral blood samples obtained from 12 historical individuals with sarcoidosis. MAIN OUTCOMES AND MEASURES Significantly differentially expressed transcripts defined as a minimum of a 1.5-fold increase or a comparable decrease and a false discovery rate of P < .05. RESULTS Signals from 2449 probe sets (transcripts from approximately 1522 genes) were significantly increased in the orbital adipose tissue from patients with sarcoidosis. Signals from 4050 probe sets (approximately 2619 genes) were significantly decreased. Signals from 3069 probe sets (approximately 2001 genes) were significantly higher and 3320 (approximately 2283 genes) were significantly lower in the lacrimal gland for patients with sarcoidosis. Ninety-two probe sets (approximately 69 genes) had significantly elevated signals and 67 probe sets (approximately 56 genes) had significantly lower signals in both orbital tissues and in peripheral blood from patients with sarcoidosis. The transcription factors, interferon-response factor 1, interferon-response factor 2, and nuclear factor κB, were strongly implicated in the expression of messenger RNA upregulated in common in the 3 tissues. CONCLUSIONS AND RELEVANCE Gene expression in sarcoidosis involving the orbit or lacrimal gland can be distinguished from gene expression patterns in control tissue and overlaps with many transcripts upregulated or downregulated in the peripheral blood of patients with sarcoidosis. These observations suggest that common pathogenic mechanisms contribute to sarcoidosis in different sites. The observations support the hypothesis that a pattern of gene expression profiles could provide diagnostic information in patients with sarcoidosis.

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Deepak P. Edward

Johns Hopkins University School of Medicine

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Valerie A. White

University of British Columbia

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