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      Review on the Management of Primary Congenital Glaucoma

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          ABSTRACT

          Despite being documented in medical history from over 2400 years ago, primary congenital glaucoma (PCG), being a disease with low incidence rate, remains a challenge to ophthalmologists.

          The article provides a broad overview on the pathophysiology and diagnostic approach to PCG with major emphasis on the treatment options of PCG. While reviewing on the well-established treatment options, namely goniotomy, trabeculo-tomy and combined trabeculotomy-trabeculectomy, emphasis has also been made to recent updates on secondary treatments: trabeculectomy, antimetabolites, glaucoma-drainage devices and cyclodestructive procedures.

          It is, however, important to note that the rarity of PCG places limitations on study design, most studies are, thus, retrospective, nonrandomized and have different definitions of surgical success. Ophthalmologists need to interpret the results with critical thinking and formulate individual treatment plans for each patient.

          How to cite this article: Yu Chan JY, Choy BNK, Alex LK Ng, Shum JWH. Review on the Management of Primary Congenital Glaucoma. J Curr Glaucoma Pract 2015;9(3):92-99.

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          Population-based assessment of childhood blindness in southern India.

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            Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma.

            To investigate CYP1B1 gene mutations in Japanese patients with primary congenital glaucoma (PCG). Sixty-five unrelated Japanese patients with PCG were screened by PCR-single-strand conformational polymorphism (SSCP) analysis followed by direct sequencing. No patients were offspring of consanguineous marriages, a common occurrence among patients in previous reports. PCG haplotypes were constructed with intragenic polymorphisms in affected individuals. Three-dimensional atomic structures of human CYP1B1 and four mutant CYP1B1 sequences representing missense mutations were assembled using homology modeling and were regularized by an energy-minimization procedure. Eleven novel mutations, including seven definite and four probable mutations, were detected in 13 (20%) of the 65 unrelated patients. Of the seven definite mutations, three were predicted to truncate the CYP1B1 open reading frame. The other four were missense mutations (Asp192Val, Ala330Phe, Val364Met, and Arg444Gln), all located in conserved core structures determining proper folding and heme-binding ability of cytochrome P450 molecules. Molecular modeling demonstrated that two of four mutations in positions 330 and 364 were structurally neutral, but Arg444Gln caused significant structural change. Of the four probable mutations, three were missense (Val198Ile, Val320Leu, and Glu499Gly); the other was a base substitution in the noncoding region of exon 1. The 11 varied CYP1B1 mutations found in 13 unrelated Japanese patients with sporadic occurrence of PCG represent an allelic heterogeneity and may be unique to a specific population.
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              Genetics and biochemistry of primary congenital glaucoma.

              Several observations noted by early investigators supported the supposition that in most cases, congenital glaucoma is determined by genetic factors. The genetic heterogeneity of PCG was confirmed by genetic linkage studies conducted in the 1990s when the authors determined that CYP1B1 is the congenital glaucoma gene at the GLC3A locus. The coding sequence of CYP1B1 has been subjected to extensive screening in familial and sporadic cases of glaucoma from numerous countries and from a large number of ethnic groups. These studies have provided evidence for extensive allelic heterogeneity at the GLC3A locus. This article also discusses the molecular evidence for reduced penetrance in congenital glaucoma and the phenotypic heterogeneity of CYP1B1 mutations, mouse models of CYP1B1, and the biochemistry of CYP1B1.
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                Author and article information

                Contributors
                Journal
                J Curr Glaucoma Pract
                J Curr Glaucoma Pract
                JOCGP
                Journal of Current Glaucoma Practice
                Jaypee Brothers Medical Publishers
                0974-0333
                0975-1947
                Sep-Dec 2015
                02 February 2016
                : 9
                : 3
                : 92-99
                Affiliations
                Clinical Assistant Professor, Department of Ophthalmology, The University of Hong Kong Hong Kong
                Clinical Assistant Professor, Department of Ophthalmology, The University of Hong Kong Hong Kong
                Clinical Assistant Professor, Department of Ophthalmology, The University of Hong Kong Hong Kong
                Clinical Assistant Professor, Department of Ophthalmology, The University of Hong Kong Hong Kong
                Author notes
                Jennifer WH Shum, Clinical Assistant Professor, Department of Ophthalmology, The University of Hong Kong, Hong Kong, Phone: 85239621405, e-mail: jenni101@hku.hk
                Article
                10.5005/jp-journals-10008-1192
                4779948
                26997844
                453559ce-35fa-4c80-98bd-76c47e25a3d4
                Copyright © 2015; Jaypee Brothers Medical Publishers (P) Ltd.

                This work is licensed under a Creative Commons Attribution 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/

                History
                : 4 September 2015
                : 28 October 2015
                Categories
                Review Article

                primary congenital glaucoma,childhood glaucoma,goniotomy,trabeculotomy,pediatric glaucoma surgery.

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