Diagnostic and Therapeutic Challenges

This case is submitted by Drs. Salvador Pastor-Idoate, Manchester Royal Eye Hospital, and Manchester Vision Regeneration (MVR) Lab at NIHR/Wellcome Trust, Manchester CRF, United Kingdom; Heinrich Heimann, Royal Liverpool and Broadgreen University Hospitals NHS Trust; Pearse A. Keane, Moorfields Eye Hospital, London, United Kingdom, and Konstantinos Balaskas; Manchester Royal Eye Hospital, Manchester, United Kingdom; commented by Dr. Brandon J. Lujan, Portland, Oregon

The T309G MDM2 gene polymorphism is a novel risk factor for proliferative vitreoretinopathy.

Proliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism (rs2279744) in PVR. Distribution of T309G MDM2 genotypes among European subjects undergoing RD surgery was evaluated. Proportions of genotypes between subsamples from different countries were analyzed. Also, a genetic interaction between rs2279744 in MDM2 and rs1042522 in p53 gene was analyzed. Significant differences were observed comparing MDM2 genotype frequencies at position 309 of intron 1 between cases (GG: 21.6%, TG: 54.5%, TT: 23.8%) and controls (GG: 7.3%, TG: 43.9%, TT: 48.7%). The proportions of genotypes between sub-samples from different countries showed a significant difference. Distribution of GG genotype revealed differences in Spain (35.1-53.0)/(22.6-32.9), Portugal (39.0-74.4)/(21.4-38.9), Netherlands (40.6-66.3)/(25.3-38.8) and UK (37.5-62.4)/(23.3-34.2). The OR of G carriers in the global sample was 5.9 (95% CI: 3.2 to 11.2). The OR of G carriers from Spain and Portugal was 5.4 (95% CI: 2.2-12.7), whereas in the UK and the Netherlands was 7.3 (95% CI: 2.8-19.1). Results indicate that the G allele of rs2279744 is associated with a higher risk of developing PVR in patients undergoing a RD surgery. Further studies are necessary to understand the role of this SNP in the development of PVR

Adrenocortical Adenoma and Central Serous Chorioretinopathy: A Rare Association

A 28-year-old man with bilateral central serous chorioretinopathy (CSCR) and body weight gain was diagnosed with Cushing’s syndrome secondary to an adrenocortical adenoma. The patient had high levels of free cortisol and the tumor was confirmed by histopathology. After surgery, cortisol levels decreased and the CSCR spontaneously resolved. This case highlights the role of cortisol in the pathogenesis of CSCR. A diagnosis of endogenous Cushing’s syndrome should be considered in patients with CSCR as an initial symptom

Advanced Ethmoid Sinus Adenocarcinoma Presenting as Temporary Exudative Retinal Detachment

We describe the case of a 70-year-old male patient with ethmoid sinus adenocarcinoma who developed an exudative retinal detachment (ERD) in the right eye as the first manifestation. Two weeks after presentation, total regression of the ERD was noted. Extensive investigations for local causes of ERD were unrewarding. Finally, we performed a computed tomography scanning of the head that revealed an ethmoidal mass extending to the orbit. The diagnosis of adenocarcinoma was confirmed by biopsy. Neoplastic phenomena should be considered in patients presenting with temporary ERD

Functional characterization of rs2229094 (T>C) polymorphism in the tumor necrosis factor locus and lymphotoxin alpha expression in human retina: the Retina 4 project

Salvador Pastor-Idoate,1,2 Irene Rodríguez-Hernández,2,3 Jimena Rojas,1 Lucia Gonzalez-Buendia,1 Santiago Delgado-Tirado,1,4 Jose Carlos López,1 Rogelio González-Sarmiento,2,3 Jose C Pastor1,4 1IOBA Eye Institute, University of Valladolid, Valladolid, 2Molecular Medicine Unit, Department of Medicine, 3Molecular and Cellular Cancer Biology Institute, High Council of Scientific Research, Biomedical Research Institute of Salamanca, University of Salamanca, Salamanca, 4Department of Ophthalmology, Hospital Clínico Universitario, Valladolid, Spain Purpose: The objective of this study is to determine the expression and localization of lymphotoxin alpha (LTA) in human retinas and the functionality of one of its polymorphisms rs2229094 (C13R) (T>C), previously associated with proliferative vitreoretinopathy (PVR) development.Materials and methods: Total RNA from three healthy human retinas were extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis, using flanking primers of LTA cDNA. In addition, three human eyes with retinal detachment (RD) and three healthy control eyes were subjected to immunohistochemistry (IHC) with a specific antibody against LTA. The functionality of T and C alleles was assessed by using pCEFL-Flag expression vector and transient transfection assays in COS-1 cell line. In addition, expression analysis by RT-PCR, Western blot and subcellular localization of both alleles and by immunofluorescence assay was performed.Results: RT-PCR analysis revealed no significant levels of messenger RNA (mRNA) LTA in healthy human retinas. Sequential IHC staining showed differences between healthy human and RD retinas. No differences in mRNA and protein expression levels and in subcellular localization between both alleles were found. Both alleles were located in the cytoplasm of COS-1 cells.Conclusion: Although results suggest lack of functionality, the differences found in IHC study and its strong association with PVR and its relationship with tumor necrosis factor locus, warrant further studies and could justify the use of this polymorphism as a valid biomarker to identify high-risk patients to develop PVR after RD. Keywords: proliferative vitreoretinopathy, lymphotoxin alpha, tumor necrosis factor alpha, inflammation, cytokines, polymorphis

Histopathological changes associated to an absorbable fibrin patch (Tachosil®) covering in an experimental model of high-risk colonic anastomoses

Background. TachoSil® is a fibrin sponge that contains fibrinogen and thrombin and is a useful adjuvant to enhance control of air leaks in thoracic surgery and to control bleeding in vascular and general surgery. Its use in intestinal surgery to prevent suture dehiscence is currently under investigation. Material and Methods. We report the results of a prospective randomized experimental study on 33 large white pigs in which a high-risk suture was created by induction of ischemia. We randomly employed TachoSil® to cover the anastomosis in half of the animals compared to a control group of uncovered anastomosis. After euthanasia, postmortem analysis was performed describing the findings related to anastomotic leakage, peritonitis and grade of adhesions. The entire anastomosis was resected in bloc and sent for histopathological analysis. A single blinded-pathologist evaluated the histopathological features of the specimens. Results. We found statistically significant differences favouring the patch in decreasing leakage in the covered group. The healing process did not show significant differences between groups, although a higher rate of microscopic abscess was observed in the covered group. Conclusion. The use of fibrin sealants covering highrisk intestinal sutures has a positive effect in avoiding macroscopic anastomotic leakage. The patch did not have any influence in the anastomotic healing process, however, as a result of the effect in containing the inflammatory response, it may increase the rate of abscess