The Open Ophthalmology Journal




ISSN: 1874-3641 ― Volume 14, 2020

Corneal Microstructural Analysis in Weill-Marchesani Syndrome by In Vivo Confocal Microscopy



Anna M Roszkowska, Pasquale Aragona*
Ophthalmology Section, Department of Surgical Specialties, University of Messina, Italy

Abstract

A thick cornea is a constant ocular finding in the mesodermal dysmorphodystrophy (Weill-Marchesani Syndrome). In this study we investigated with confocal microscopy, the corneal structure in vivo in the patient affected by Weill-Marchesani Syndrome (WMS) in an attempt to explain the thickness increment. The corneal study showed in both eyes a highly increased central thickness with normal topography and sensitivity. The confocal examination revealed an increased evidence of keratocytes in the anterior stroma with abnormal and activated appearance. The mid and deep stroma and endothelial layer were normal. These confocal findings are a newly described feature of corneal involvement in WMS. The increase of the corneal thickness in the affected patient maybe associated with connective tissue alterations, such as abnormal collagen synthesis, that characterizes the disease.

Keywords: Weill- Marchesani syndrome, cornea, keratocytes, in vivo confocal microscopy.


Article Information


Identifiers and Pagination:

Year: 2011
Volume: 5
First Page: 48
Last Page: 50
Publisher Id: TOOPHTJ-5-48
DOI: 10.2174/1874364101105010048

Article History:

Received Date: 20/11/2010
Revision Received Date: 27/4/2011
Acceptance Date: 28/4/2011
Electronic publication date: 01/06/2011
Collection year: 2011

© Roszkowska and Aragona; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.


* Address correspondence to this author at the Department of Surgical Specialties, Section of Ophthalmology, University of Messina, Policlinico Universitario, I-98125, Messina, Italy; Tel: +39-90-2212972; Fax: +39-90-692449; E-mail: paragona@unime.it





INTRODUCTION

Weill-Marchesani Syndrome (WMS), also called mesodermal dysmorphodystrophy, is a systemic connective tissue disorder related to the altered encoding for protein of extracellular matrix with fibrous tissue hyperplasia [1Dagoneau N, Benoist-Lasselin C, Huber C, et al. ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome Am J Hum Genet 2004; 75: 801-6.]. The disease is genetically determined with both autosomal dominant and recessive inheritance modalities and exhibit clinical homogenous features, despite genetic heterogeneity. The diagnosis is based on clinical findings such as short stature, brachycephaly, stiff joints; ocular abnormalities include short axial length, shallow anterior chamber, microspherophakia, with high lenticular myopia, and ectopia lentis [2Razeghinejad MR, Hosseini H, Namazi N. Biometric and corneal topographic characteristic in patients with Weill-Marchesani syndrome J Cataract Refract Surg 2009; 35(6): 1026-8.]. The constant corneal finding is an increased central thickness, of yet unexplained origin [2Razeghinejad MR, Hosseini H, Namazi N. Biometric and corneal topographic characteristic in patients with Weill-Marchesani syndrome J Cataract Refract Surg 2009; 35(6): 1026-8., 3Razeghinejad MR, Safavian H. Central corneal thickness in patients with Weill-Marchesani syndrome Am J Ophthalmol 2006; 142: 507-8.].

In this study we have investigated the corneal structure by in vivo confocal microscopy, in a patient with WMS, in the attempt to explain the thickness increment. As to our knowledge this is the first report concerning corneal in vivo confocal examination in eyes with WMS.

CASE REPORT

We examined a 19-year-old male referred to the Cornea Unit of the Ophthalmology Clinic of the University of Messina, Messina, Italy, to undergo laser refractive surgery. The patient presented with short stature, high myopia, thick cornea (618 microns in the RE and 622 microns in the LE), shallow anterior chamber (2.75 mms and 2.55 mms respectively), small thick lens (5.0 mms and 4.9mms in the RE and LE), and short axial length (22.01 mms and 21.97 mms). On the basis of these findings the clinical diagnosis of WMS was posed. The patient was a soft contact lens wearer up to two month prior to the visit.

The corneal structure was examined by confocal microscopy (Confoscan 4, Nidek Technologies, Italy). Confocal investigation showed normal epithelial layers characterized by basal cells with bright borders and dark cell bodies and well represented superficial nerves (Fig.1A, B). In the anterior stroma, the keratocytes shape varied showing small and elongated cells with irregular bodies, frequently clustered and activated (Fig. 1C, D); the mid and deep stroma were normal (Fig. 1E). We considered ten photographs of anterior and posterior stroma of each eye to determine the keratocytes density. It was found to be 1228.2 ± 77.15 cell/mm2 in the anterior stroma of the RE and 1180.35 ± 63.54 cell/mm2 in the LE; in the posterior stroma it was 582.07± 75.47 cell/mm2 in the RE and 583.75 ± 29.89 cell/mm2 in the LE. Corneal endothelium was normal in both eyes with the mean cell density of 3461 cell/mm2 in the RE and 3405 cell/mm2 in the LE respectively (Fig. 1F).

Fig. (1)

Confocal images in WMS patient. Bar represents 100μm. (A) Normal basal epithelium with dark cell bodies and bright borders. (B) Sub-epithelial layer with normal nerves fibers. (C, D) Superficial stroma. Abnormally shaped, clustered keratocytes with presence of activated cells. (E) Deep stroma with normal keratocytes. (F) Corneal endothelium with normal cell morphology and density.



Fig. (2)

Confocal images in normal eye. Bar represents 100μm. (A) Superficial stroma. (B) Deep stroma.



Furthermore, we have examined 10 eyes of 10 age matched healthy subjects who were soft contact lenses wearers, to compare the confocal corneal findings. In this group the mean keratocyte density in the anterior stroma resulted to be 760.4 cell/mm2 and in the posterior stroma 563.6 cell/mm2 respectively (Fig. 2A, B).

DISCUSSION

Ocular findings such as short axial length, shallow anterior chamber, and thick lens were already described in WMS as well as the excessive corneal thickness, the origin of which is unknown. The purpose of this study was to investigate the cornea in vivo, by confocal microscopy, in the attempt to identify the changes that might help to explain corneal features in WMS [2Razeghinejad MR, Hosseini H, Namazi N. Biometric and corneal topographic characteristic in patients with Weill-Marchesani syndrome J Cataract Refract Surg 2009; 35(6): 1026-8., 3Razeghinejad MR, Safavian H. Central corneal thickness in patients with Weill-Marchesani syndrome Am J Ophthalmol 2006; 142: 507-8.]. Confocal microscopy showed normal endothelium and deep stroma. The normality of the corneal endothelium, responsible for corneal hydratation and transparency maintenance is relevant because it allows the exclusion of endothelial involvement in the CCT increase in WMS. The main confocal finding is the abnormal cell population in the superficial stroma, consisting of activated and abnormally shaped keratocytes with an increased density. In fact the reported normal values for normal population are between 804±15 cell/mm2 to 1060±47 cell/mm2 for the anterior stroma and 480±67 cell/mm2 and 771±14 cell/mm2 for the posterior stroma, respectively [4Patel DV, Mc Ghee CNJ. Contemporary in vivo confocal microscopy of the living human cornea using white light and laser scanning techniques: a major review Clin Exp Ophthalmol 2007; 35: 71-88.]. The keratocytes density calculated in both anterior and posterior stroma in the control group exhibited such normal values. Therefore, it appears that in our patient, beside a normal cellular population in the posterior stroma, there is an alteration of the cellular pattern localized in the anterior stroma.

Beside the increased keratocytes density the presence of activated cells acquiring fibroblastic characteristics could indicate an increased metabolic activity and collagen synthesis. As an abnormal collagen synthesis is at a basis of WMS, the abnormalities of the anterior corneal stroma evidenced in this study, could possibly be attributed to the connective tissue alterations that characterize the disease, and help to explain the increase of the corneal thickness in affected patients. This is the first report of in vivo confocal corneal investigation in mesodermal dysmorphodystrophy. Further investigations involving a larger number of WMS subjects would be useful to confirm the anterior stroma alterations in the cornea of the affected patients.

REFERENCES

[1] Dagoneau N, Benoist-Lasselin C, Huber C, et al. ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome Am J Hum Genet 2004; 75: 801-6.
[2] Razeghinejad MR, Hosseini H, Namazi N. Biometric and corneal topographic characteristic in patients with Weill-Marchesani syndrome J Cataract Refract Surg 2009; 35(6): 1026-8.
[3] Razeghinejad MR, Safavian H. Central corneal thickness in patients with Weill-Marchesani syndrome Am J Ophthalmol 2006; 142: 507-8.
[4] Patel DV, Mc Ghee CNJ. Contemporary in vivo confocal microscopy of the living human cornea using white light and laser scanning techniques: a major review Clin Exp Ophthalmol 2007; 35: 71-88.
Track Your Manuscript:


Endorsements



"Open access will revolutionize 21st century knowledge work and accelerate the diffusion of ideas and evidence that support just in time learning and the evolution of thinking in a number of disciplines."


Daniel Pesut
(Indiana University School of Nursing, USA)

"It is important that students and researchers from all over the world can have easy access to relevant, high-standard and timely scientific information. This is exactly what Open Access Journals provide and this is the reason why I support this endeavor."


Jacques Descotes
(Centre Antipoison-Centre de Pharmacovigilance, France)

"Publishing research articles is the key for future scientific progress. Open Access publishing is therefore of utmost importance for wider dissemination of information, and will help serving the best interest of the scientific community."


Patrice Talaga
(UCB S.A., Belgium)

"Open access journals are a novel concept in the medical literature. They offer accessible information to a wide variety of individuals, including physicians, medical students, clinical investigators, and the general public. They are an outstanding source of medical and scientific information."


Jeffrey M. Weinberg
(St. Luke's-Roosevelt Hospital Center, USA)

"Open access journals are extremely useful for graduate students, investigators and all other interested persons to read important scientific articles and subscribe scientific journals. Indeed, the research articles span a wide range of area and of high quality. This is specially a must for researchers belonging to institutions with limited library facility and funding to subscribe scientific journals."


Debomoy K. Lahiri
(Indiana University School of Medicine, USA)

"Open access journals represent a major break-through in publishing. They provide easy access to the latest research on a wide variety of issues. Relevant and timely articles are made available in a fraction of the time taken by more conventional publishers. Articles are of uniformly high quality and written by the world's leading authorities."


Robert Looney
(Naval Postgraduate School, USA)

"Open access journals have transformed the way scientific data is published and disseminated: particularly, whilst ensuring a high quality standard and transparency in the editorial process, they have increased the access to the scientific literature by those researchers that have limited library support or that are working on small budgets."


Richard Reithinger
(Westat, USA)

"Not only do open access journals greatly improve the access to high quality information for scientists in the developing world, it also provides extra exposure for our papers."


J. Ferwerda
(University of Oxford, UK)

"Open Access 'Chemistry' Journals allow the dissemination of knowledge at your finger tips without paying for the scientific content."


Sean L. Kitson
(Almac Sciences, Northern Ireland)

"In principle, all scientific journals should have open access, as should be science itself. Open access journals are very helpful for students, researchers and the general public including people from institutions which do not have library or cannot afford to subscribe scientific journals. The articles are high standard and cover a wide area."


Hubert Wolterbeek
(Delft University of Technology, The Netherlands)

"The widest possible diffusion of information is critical for the advancement of science. In this perspective, open access journals are instrumental in fostering researches and achievements."


Alessandro Laviano
(Sapienza - University of Rome, Italy)

"Open access journals are very useful for all scientists as they can have quick information in the different fields of science."


Philippe Hernigou
(Paris University, France)

"There are many scientists who can not afford the rather expensive subscriptions to scientific journals. Open access journals offer a good alternative for free access to good quality scientific information."


Fidel Toldrá
(Instituto de Agroquimica y Tecnologia de Alimentos, Spain)

"Open access journals have become a fundamental tool for students, researchers, patients and the general public. Many people from institutions which do not have library or cannot afford to subscribe scientific journals benefit of them on a daily basis. The articles are among the best and cover most scientific areas."


M. Bendandi
(University Clinic of Navarre, Spain)

"These journals provide researchers with a platform for rapid, open access scientific communication. The articles are of high quality and broad scope."


Peter Chiba
(University of Vienna, Austria)

"Open access journals are probably one of the most important contributions to promote and diffuse science worldwide."


Jaime Sampaio
(University of Trás-os-Montes e Alto Douro, Portugal)

"Open access journals make up a new and rather revolutionary way to scientific publication. This option opens several quite interesting possibilities to disseminate openly and freely new knowledge and even to facilitate interpersonal communication among scientists."


Eduardo A. Castro
(INIFTA, Argentina)

"Open access journals are freely available online throughout the world, for you to read, download, copy, distribute, and use. The articles published in the open access journals are high quality and cover a wide range of fields."


Kenji Hashimoto
(Chiba University, Japan)

"Open Access journals offer an innovative and efficient way of publication for academics and professionals in a wide range of disciplines. The papers published are of high quality after rigorous peer review and they are Indexed in: major international databases. I read Open Access journals to keep abreast of the recent development in my field of study."


Daniel Shek
(Chinese University of Hong Kong, Hong Kong)

"It is a modern trend for publishers to establish open access journals. Researchers, faculty members, and students will be greatly benefited by the new journals of Bentham Science Publishers Ltd. in this category."


Jih Ru Hwu
(National Central University, Taiwan)


Browse Contents



Table of Contents


Webmaster Contact: info@benthamopen.net
Copyright © 2020 Bentham Open