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Vitiello L, Lixi F, Coppola A, Abbinante G, Gagliardi V, Salerno G, De Pascale I, Pellegrino A, Giannaccare G. Intravitreal Dexamethasone Implant Switch after Anti-VEGF Treatment in Patients Affected by Retinal Vein Occlusion: A Review of the Literature. J Clin Med 2024; 13:5006. [PMID: 39274219 PMCID: PMC11395781 DOI: 10.3390/jcm13175006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/16/2024] Open
Abstract
Nowadays, retinal vein occlusion (RVO) is the second most prevalent cause of vision loss associated with retinal vascular disease. Intravitreal injections are currently known as a major advancement in ophthalmology, particularly in the treatment of RVO and other retinal disorders. Particularly, the first line of therapy is usually anti-vascular endothelial growth factor (VEGF) drugs. Notably, for RVO eyes that have not responded to anti-VEGF therapy, an intravitreal dexamethasone (DEX) implant 0.7 mg (Ozurdex®, AbbVie Inc., North Chicago, IL, USA) is considered a suitable therapeutical substitute. Actually, investigations carried out in the real world and clinical trials have shown the safety and the efficacy of intravitreal DEX implants for treating this retinal disease. For this reason, choosing patients carefully may thus be essential to reduce the number of injections that clinics and hospitals have to do to manage RVO and its complications. The primary aim of this review is to summarize the pathophysiology of this retinal vascular disease, as well as the clinical and ocular imaging features that may support a switch from prior anti-VEGF treatment to intravitreal DEX implant, to provide the RVO patients with the best possible treatment to ensure maximum visual recovery.
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Affiliation(s)
- Livio Vitiello
- Eye Unit, "Luigi Curto" Hospital, Azienda Sanitaria Locale Salerno, 84035 Polla, SA, Italy
| | - Filippo Lixi
- Eye Clinic, Department of Surgical Sciences, University of Cagliari, 09124 Cagliari, CA, Italy
| | - Alessia Coppola
- Eye Unit, "Luigi Curto" Hospital, Azienda Sanitaria Locale Salerno, 84035 Polla, SA, Italy
| | - Giulia Abbinante
- Eye Unit, "Luigi Curto" Hospital, Azienda Sanitaria Locale Salerno, 84035 Polla, SA, Italy
| | - Vincenzo Gagliardi
- Eye Unit, "Luigi Curto" Hospital, Azienda Sanitaria Locale Salerno, 84035 Polla, SA, Italy
| | - Giulio Salerno
- Eye Unit, "Luigi Curto" Hospital, Azienda Sanitaria Locale Salerno, 84035 Polla, SA, Italy
| | - Ilaria De Pascale
- Eye Unit, "Luigi Curto" Hospital, Azienda Sanitaria Locale Salerno, 84035 Polla, SA, Italy
| | - Alfonso Pellegrino
- Eye Unit, "Luigi Curto" Hospital, Azienda Sanitaria Locale Salerno, 84035 Polla, SA, Italy
| | - Giuseppe Giannaccare
- Eye Clinic, Department of Surgical Sciences, University of Cagliari, 09124 Cagliari, CA, Italy
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Mruthunjaya AKV, Torriero AAJ. Electrochemical Monitoring in Anticoagulation Therapy. Molecules 2024; 29:1453. [PMID: 38611733 PMCID: PMC11012951 DOI: 10.3390/molecules29071453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 03/16/2024] [Accepted: 03/22/2024] [Indexed: 04/14/2024] Open
Abstract
The process of blood coagulation, wherein circulating blood transforms into a clot in response to an internal or external injury, is a critical physiological mechanism. Monitoring this coagulation process is vital to ensure that blood clotting neither occurs too rapidly nor too slowly. Anticoagulants, a category of medications designed to prevent and treat blood clots, require meticulous monitoring to optimise dosage, enhance clinical outcomes, and minimise adverse effects. This review article delves into the various stages of blood coagulation, explores commonly used anticoagulants and their targets within the coagulation enzyme system, and emphasises the electrochemical methods employed in anticoagulant testing. Electrochemical sensors for anticoagulant monitoring are categorised into two types. The first type focuses on assays measuring thrombin activity via electrochemical techniques. The second type involves modified electrode surfaces that either directly measure the redox behaviours of anticoagulants or monitor the responses of standard redox probes in the presence of these drugs. This review comprehensively lists different electrode compositions and their detection and quantification limits. Additionally, it discusses the potential of employing a universal calibration plot to replace individual drug-specific calibrations. The presented insights are anticipated to significantly contribute to the sensor community's efforts in this field.
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Affiliation(s)
| | - Angel A. J. Torriero
- School of Life and Environmental Sciences, Deakin University, Burwood 3125, Australia
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Teodoru CA, Munteanu M, Mercea N, Moatar A, Stanca H, Popescu FG, Dura H, Hașegan A, Giurgiu DI, Cerghedean-Florea ME. Ophthalmic Vein Thrombosis Associated with Factor V Leiden and MTHFR Mutations. Diagnostics (Basel) 2023; 13:diagnostics13061052. [PMID: 36980359 PMCID: PMC10047011 DOI: 10.3390/diagnostics13061052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/03/2023] [Accepted: 03/06/2023] [Indexed: 03/12/2023] Open
Abstract
Superior ophthalmic vein thrombosis (SOVT) is a rare clinical entity that may be associated with hypercoagulability status. We present a case of a 77-year-old woman who presented to the emergency department complaining of eye ptosis, chemosis and conjunctival congestion in the right eye (RE). The ophthalmological examination revealed best-corrected visual acuity (BCVA) was 0.5 for the right eye (RE) 0.5 and 0.06 for the left eye (LE). Intraocular pressure (IOP) was 25 mmHg in RE and 14 mmHg in LE. Non-contrast computed tomography (CT) of the brain and orbits revealed a hyperreflectivity at the level of the right ophthalmic vein and inferior rectus muscle hypertrophy. An extensive hypercoagulable panel was completed and we found a positive result for Factor V Leiden (heterozygous mutation) and methyl-enetetrahydrofolate reductase (MTHFR-C677T homozygous mutations). Systemic steroidal anti-inflammatory and anticoagulant treatments were started immediately. Gradual resolution of symptoms was noted during the hospitalization, and BCVA in her RE was established at 0.7 at the 10-week follow-up.
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Affiliation(s)
| | - Mihnea Munteanu
- Department of Ophthalmology, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Nadina Mercea
- Ophthalmology Clinic, Municipal Clinical Emergency Hospital, 300254 Timisoara, Romania
| | - Alina Moatar
- Ophthalmology Clinic, Municipal Clinical Emergency Hospital, 300254 Timisoara, Romania
| | - Horia Stanca
- Department of Ophthalmology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
| | - Florina Georgeta Popescu
- Department of Occupational Medicine, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Horațiu Dura
- Faculty of Medicine, “Lucian Blaga” University Sibiu, 550169 Sibiu, Romania
| | - Adrian Hașegan
- Faculty of Medicine, “Lucian Blaga” University Sibiu, 550169 Sibiu, Romania
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Romiti GF, Corica B, Borgi M, Visioli G, Pacella E, Cangemi R, Proietti M, Basili S, Raparelli V. Inherited and acquired thrombophilia in adults with retinal vascular occlusion: A systematic review and meta-analysis. J Thromb Haemost 2020; 18:3249-3266. [PMID: 32805772 DOI: 10.1111/jth.15068] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 07/19/2020] [Accepted: 08/12/2020] [Indexed: 01/15/2023]
Abstract
BACKGROUND Retinal vascular occlusion is a leading cause of sight loss. Both retinal artery occlusion (RAO) and retinal vein occlusion (RVO) have been associated with hypercoagulable states; however, the burden of thrombophilia in these patients is unclear. OBJECTIVES This study aims at estimating the prevalence of inherited and acquired thrombophilias in adults with RAO or RVO through a systematic review and meta-analysis of the literature. PATIENTS/METHODS PubMed and EMBASE were systematically searched from inception to 29 February 2020. All studies reporting prevalences of factor V Leiden (FVL) and prothrombin (F-II) G20210A mutations, methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor (PAI) 4G polymorphisms, antithrombin III (AT-III), protein C (PC) and protein S (PS) activity deficiencies, hyperhomocysteinemia, and antiphospholipid (APL) antibodies in adults with RAO or RVO were included. Pooled prevalences and 95% confidence intervals (CI) were calculated. RESULTS Ninety-five studies were included; FVL and F-II mutations were found in 6% (95% CI: 5-8) and 3% (95% CI: 2-4) of individuals with RVO, respectively, whereas AT-III, PC, and PS activity deficiencies were found in <2%. The MTHFR C677T and PAI 4G homozygous polymorphism were observed in 13% (95% CI: 10-17) and 23% (95% CI: 16-31) of RVO, respectively; 8% presented APL antibodies. Similar findings were observed in individuals with RAO. CONCLUSIONS Compared with healthy subjects, patients with retinal vascular occlusion showed similar prevalences of inherited and acquired thrombophilias. These findings do not support routine thrombophilia screening in individuals with RAO or RVO.
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Affiliation(s)
- Giulio Francesco Romiti
- Department of Translational and Precision Medicine, Sapienza - University of Rome, Rome, Italy
| | - Bernadette Corica
- Department of Translational and Precision Medicine, Sapienza - University of Rome, Rome, Italy
| | - Marco Borgi
- Department of Translational and Precision Medicine, Sapienza - University of Rome, Rome, Italy
| | - Giacomo Visioli
- Department of Sense Organs, Sapienza - University of Rome, Rome, Italy
| | - Elena Pacella
- Department of Sense Organs, Sapienza - University of Rome, Rome, Italy
| | - Roberto Cangemi
- Department of Translational and Precision Medicine, Sapienza - University of Rome, Rome, Italy
| | - Marco Proietti
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
- Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, UK
| | - Stefania Basili
- Department of Translational and Precision Medicine, Sapienza - University of Rome, Rome, Italy
| | - Valeria Raparelli
- Department of Experimental Medicine, Sapienza - University of Rome, Rome, Italy
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Antman G, Keren S, Kurtz S, Rosenblatt A, Rachmiel R. The Incidence of Retinal Vein Occlusion in Patients with Pseudoexfoliation Glaucoma: A Retrospective Cohort Study. Ophthalmologica 2018; 241:130-136. [PMID: 30391951 DOI: 10.1159/000492401] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Accepted: 07/23/2018] [Indexed: 01/04/2023]
Abstract
PURPOSE The aim of this study was to evaluate pseudoexfoliation (PXF) as an independent risk factor for the occurrence of retinal vein occlusion (RVO). METHODS This is a retrospective cohort study on the records of 300 PXF glaucoma patients (PXF group), 300 non-PXF glaucoma patients, and 599 nonglaucoma non-PXF (nGnP group) patients. RESULTS Multivariate analysis resulted in a significant probability for RVO in the PXF (p = 0.005; OR 2.29 [1.13-4.68]) and non-PXF glaucoma groups (p = 0.005; OR 3.03 [1.55-5.94]) compared to the nGnP group. There was a much higher probability for central RVO (CRVO) in the PXF (p = 0.013; OR 3.64 [1.39-9.49]) and non-PXF glaucoma groups (p = 0.013; OR 3.78 [1.48-9.65]) compared to the nGnP group. After matching and excluding neovascular glaucoma, no significant difference was found between the PXF and non-PXF glaucoma groups regarding RVO (p = 0.541), CRVO (p = 0.092), and branch RVO (p = 0.774). CONCLUSIONS PXF and other types of glaucoma are associated with RVOs, mainly CRVO. PXF was not found to be an independent risk factor for CRVO.
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Affiliation(s)
- Gal Antman
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shay Keren
- Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, .,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel,
| | - Shimon Kurtz
- Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Amir Rosenblatt
- Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Rony Rachmiel
- Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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Bohm KJ, Gobin YP, Francis JH, McInerney G, Dabo-Trubelja A, Dalecki PH, Marr BP, Abramson DH. Choroidal infarction following ophthalmic artery chemotherapy. Int J Retina Vitreous 2018; 4:16. [PMID: 29736261 PMCID: PMC5925835 DOI: 10.1186/s40942-018-0119-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 03/30/2018] [Indexed: 12/13/2022] Open
Abstract
Background Methylenetetrahydrofolate reductase (MTHFR) genetic mutations and intra-procedural inhaled nitrous oxide (N2O) independently increase blood levels of homocysteine, a compound associated with thrombosis. Patients with MTHFR mutations who also receive N2O during ophthalmic artery chemotherapy (OAC) for retinoblastoma may have a heightened thrombotic risk. Case presentations Single-center retrospective review of pediatric patients with advanced retinoblastoma who received OAC and developed choroidal infarcts. Four retinoblastoma patients with advanced intraocular disease (2 males, 2 females: 13-58 months) experienced choroidal infarcts within the one-month period after OAC, in which procedural N2O induction was used (duration between 21 and 58 min). All 4 patients had MTHFR (chromosome 1p, position 36.22) genetic abnormalities: one was homozygous for the C677T mutation, one was C677T heterozygous, one was A1298C heterozygous, and one was heterozygous for both C677T and A1298C. In all 4 patients, indirect ophthalmoscopy and fundus photography showed marked disturbance of the retinal pigment epithelium and optical coherence tomography (OCT) confirmed thinning of the choroid. Follow-up time ranged from 15 to 46 months (median 21 months). Conclusions Choroidal infarction in eyes treated with OAC developed in children who were both deficient in at least one working allele of the MTHFR gene (heterozygous or homozygous) and received N2O induction during OAC.
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Affiliation(s)
- Kelley J Bohm
- 1Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Room A330, New York, NY 10065 USA
| | - Y Pierre Gobin
- 2Interventional Neuroradiology, Departments of Radiology and Neurosurgery, Weill Cornell Medical Center/New York Presbyterian Hospital, New York, NY USA
| | - Jasmine H Francis
- 1Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Room A330, New York, NY 10065 USA
| | - Gabrielle McInerney
- 3Department of Anesthesiology, Weill Cornell Medical Center/New York Presbyterian Hospital, New York, NY USA
| | - Anahita Dabo-Trubelja
- 4Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY USA
| | - Paul H Dalecki
- 4Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY USA
| | - Brian P Marr
- 1Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Room A330, New York, NY 10065 USA
| | - David H Abramson
- 1Ophthalmic Oncology Service, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Room A330, New York, NY 10065 USA
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Abstract
Retinal vein occlusions are the second most common form of retinal vascular disease. Previously, laser treatment for branch retinal vein occlusion and intravitreal triamcinolone acetonide for central retinal vein occlusion were the standard of care. Recent studies have demonstrated that anti-vascular endothelial growth factor (anti-VEGF) agents have a superior safety and efficacy profile for the treatment of both branch and central retinal vein occlusions. The use of wide-field fluorescein angiography has also allowed better visualization of the retinal periphery. Despite the better documentation of retinal non-perfusion, laser photocoagulation to the areas of non-perfusion does not seem to result in a reduction of macular edema or reduction in treatment burden and has been relegated to patients who develop rubeosis or neovascularization of the retina. More recently, several studies have demonstrated the use of a long-acting dexamethasone implant administered intravitreally or triamcinolone administered in the suprachoroidal space as a viable approach to treat retinal vein occlusion.
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Affiliation(s)
- Daniel D Esmaili
- Retina-Vitreous Associates Medical Group, 001 Wilshire Boulevard, Suite 301, Beverly Hills, CA 90211, USA
| | - David S Boyer
- Retina-Vitreous Associates Medical Group, 001 Wilshire Boulevard, Suite 301, Beverly Hills, CA 90211, USA.,Keck School of Medicine, University of Southern California, 1975 Zonal Avenue, Los Angeles, CA 90033, USA
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Sodi A, Giambene B, Falaschi G, Caputo R, Innocenti B, Corvi A, Menchini U. Ocular Surface Temperature in Central Retinal Vein Occlusion: Preliminary Data. Eur J Ophthalmol 2018; 17:755-9. [DOI: 10.1177/112067210701700511] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Affiliation(s)
| | | | - G. Falaschi
- Department of Mechanics and Industrial Technology, University of Firenze, Firenze
| | - R. Caputo
- Pediatric Ophthalmology Unit, A. Meyer Children Hospital, Firenze - Italy
| | - B. Innocenti
- Department of Mechanics and Industrial Technology, University of Firenze, Firenze
| | - A. Corvi
- Department of Mechanics and Industrial Technology, University of Firenze, Firenze
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Nema N, Verma S, Kumar R. Investigation of methylenetetrahydrofolate reductase C677T and factor V Leiden mutation as a genetic marker for retinal vein occlusion. Taiwan J Ophthalmol 2018; 8:99-103. [PMID: 30038889 PMCID: PMC6055313 DOI: 10.4103/tjo.tjo_43_17] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
PURPOSE: Thromboembolic phenomenon is one of the causes of retinal vein occlusion (RVO) which is in fact a multifactorial disease. Therefore, we aimed to study methylenetetrahydrofolate reductase gene polymorphism (MTHFR C677T) and factor V Leiden as genetic risk factors of RVO. MATERIALS AND METHODS: A total of 50 (19 males and 31 females) cases of RVO were compared with 50 age- and sex-matched (21 males and 29 females) controls. Complete ocular examination was done for all samples. The diagnosis of RVO was made clinically; however, fundus fluorescein angiography and optical coherence tomography were performed when needed. Serum homocysteine levels were estimated by automatic chemiluminescence analyzer, whereas MTHFR C677T and factor V Leiden mutations were detected by polymerase chain reaction–restriction fragment length polymorphism method. RESULTS: The mean age of RVO cases and controls was 54.62 ± 13.92 years and 58.72 ± 11.20 years, respectively. 48.3% of cases and 51.7% of controls were diabetic. 65.3% of cases were hypertensive proving hypertension as a strong risk factor (P = 0.003) of RVO. Serum homocysteine was also found significantly high (P = 0.025) with mean values of 19.98 ± 9.03 μmol/L and 16.98 ± 8.29 μmol/L in cases and controls, respectively. The MTHFR genotype (CT) was found in 83.3% patients of central RVO group and 78.6% cases of branch RVO group that was significantly associated with high serum homocysteine levels. Factor V Leiden mutation was absent in all individuals. CONCLUSION: Hyperhomocysteinemia is an important risk factor for RVO, especially in patients with MTHFR C677T gene polymorphism.
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Affiliation(s)
- Nitin Nema
- Department of Ophthalmology, Sri Aurobindo Medical College and Post Graduate Institute, Indore, Madhya Pradesh, India
| | - Sonam Verma
- Department of Ophthalmology, Sri Aurobindo Medical College and Post Graduate Institute, Indore, Madhya Pradesh, India
| | - Ravindra Kumar
- Central Research Laboratory, Sri Aurobindo Medical College and Post Graduate Institute, Indore, Madhya Pradesh, India.,Department of Genetics, ICMR-National Institute for Research in Tribal Health, Jabalpur, Madhya Pradesh, India
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Sinawat S, Bunyavee C, Ratanapakorn T, Sinawat S, Laovirojjanakul W, Yospaiboon Y. Systemic abnormalities associated with retinal vein occlusion in young patients. Clin Ophthalmol 2017; 11:441-447. [PMID: 28260858 PMCID: PMC5328302 DOI: 10.2147/opth.s128341] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
OBJECTIVES To study the systemic abnormalities associated with retinal vein occlusion in patients aged ≤50 years with a particular emphasis on atherosclerotic diseases and thrombophilic disorders. METHODS Medical charts of patients, aged ≤50 years whose diagnoses were retinal vein occlusions during the period 1995-2015 were retrospectively reviewed. The primary outcome was the number of systemic abnormalities associated with these patients. Secondary outcomes included types of retinal vein occlusion and sites of occlusion. RESULTS Atherosclerotic diseases were the most common systemic abnormalities associated with retinal vein occlusion and accounted for 55.1% of the patients in the study. Hypertension in 27.55%, diabetes mellitus in 16.33%, and 5.1% with dyslipidemia were noted. The number of thrombophilic disorders seemed to be less than expected and were noted in only 5.1%. Other systemic abnormalities included viral hepatitis infection, systemic lupus erythematosus, and acquired immunodeficiency syndrome. Oral contraceptives were used by some patients. CONCLUSION Atherosclerotic diseases remained the most commonly associated systemic diseases in the majority of these patients. Approach to these patients should include a screening for hypertension, diabetes mellitus, and lipid abnormalities. Thrombophilia should also be considered where no obvious atherosclerotic diseases are found or if the patient is <40 years old, a history of thrombosis or a family history of thrombosis is possible.
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Affiliation(s)
- Suthasinee Sinawat
- KKU Eye Center, Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Chavisa Bunyavee
- Department of Ophthalmology, Faculty of Medicine, Nawamindaradhiraj University, Bangkok, Thailand
| | - Tanapat Ratanapakorn
- KKU Eye Center, Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Supat Sinawat
- Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Wipada Laovirojjanakul
- KKU Eye Center, Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Yosanan Yospaiboon
- KKU Eye Center, Department of Ophthalmology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
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12
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Kirkegaard K, Heegaard S, Hvas AM. No evidence for thrombophilia in patients with retinal venous occlusion: a systematic GRADE-based review. Acta Ophthalmol 2017; 95:12-19. [PMID: 27573507 DOI: 10.1111/aos.13214] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Accepted: 06/30/2016] [Indexed: 11/28/2022]
Abstract
Retinal venous occlusion represents a common retinal disorder that untreated often leads to severely reduced vision. While general risk factors for vascular disease are known to increase the risk of an event, the role of thrombophilia is controversial. The purpose of this systematic review was to evaluate the evidence for thrombophilia investigation in patients presenting with retinal venous occlusion. Eligible studies were identified by a MESH-based search in PubMed 11-13 of March 2015. The level of evidence was stated according to the guidelines published by the GRADE working group using three levels for quality of evidence: high, moderate and low. A total of 118 studies relating to the study question were identified. After excluding case stories, commentaries, cross-sectional studies and reviews/expert opinions, 28 original papers and two meta-analyses were included in the final qualitative synthesis. The majority of studies were small case-control studies, and only one large cohort study was identified. No randomized controlled trials were retrieved. All the studies were categorized as low quality of evidence. Systematic thrombophilia screening in patients presenting with retinal venous occlusion cannot be recommended.
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Affiliation(s)
- Kirstine Kirkegaard
- Department of Clinical Biochemistry; Aarhus University Hospital; Aarhus Denmark
| | - Steffen Heegaard
- Departments of Ophthalmology and Pathology; Rigshospitalet; University of Copenhagen; Copenhagen Denmark
| | - Anne-Mette Hvas
- Department of Clinical Biochemistry; Aarhus University Hospital; Aarhus Denmark
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13
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Li M, Hu X, Huang J, Tan Y, Yang B, Tang Z. Impact of Retinal Vein Occlusion on Stroke Incidence: A Meta-Analysis. J Am Heart Assoc 2016; 5:JAHA.116.004703. [PMID: 28007745 PMCID: PMC5210429 DOI: 10.1161/jaha.116.004703] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Background Considerable controversy exists on the association between retinal vein occlusion (RVO) and stroke risk. Therefore, we conducted a meta‐analysis to assess the relationship between RVO and stroke risk. Methods and Results PubMed, EMBASE, and the Cochrane library databases were searched for cohort studies with data on RVO and stroke risk. Studies that reported adjusted relative risks (RRs) with 95% CIs of stroke associated with RVO were included. Stratified analyses were conducted according to key characteristics. A total of 5 articles including results from 6 prospective cohort studies with 431 cases of stroke and 37 471 participants were included in the meta‐analysis. Overall, after adjustment for established cardiovascular risk factors, participants with RVO at baseline were considerably more associated with a greater incidence of stroke risk (combined RR: 1.50, 95% CI: 1.19–1.90), compared to participants without RVO. The results were more pronounced for stroke (RR: 1.72, 95% CI: 1.24–2.37) in the stratified with a stroke history. The risk of stroke was nonsignificant in male subjects (RR: 1.20, 95% CI: 0.96–1.49) and in female subjects (RR: 0.93, 95% CI: 0.64–1.34). The presence of both central RVO (RR: 1.90, 95% CI: 1.46–2.48) and branch RVO (RR: 1.79, 95% CI: 1.18–2.72) was associated with increased risk of stroke. Stratifying by age, the associations between RVO and risk of stroke were similar between the age range in the cohorts that ranged from 50 to 59 years and 60 to 69 years. Conclusions Exposure to RVO was associated with an increased risk of stroke, especially in subjects aged between 50 and 69 years. Future studies on the effect of RVO treatment and modifiable risk factor reduction on stroke risk in RVO patients are warranted.
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Affiliation(s)
- Min Li
- Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Xiaolan Hu
- Department of Anaesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jiangtao Huang
- Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yuan Tan
- Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Baoping Yang
- Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhenyu Tang
- Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
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Dixon SG, Bruce CT, Glueck CJ, Sisk RA, Hutchins RK, Jetty V, Wang P. Retinal vascular occlusion: a window to diagnosis of familial and acquired thrombophilia and hypofibrinolysis, with important ramifications for pregnancy outcomes. Clin Ophthalmol 2016; 10:1479-86. [PMID: 27563233 PMCID: PMC4984829 DOI: 10.2147/opth.s106969] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Aim Our specific aim was to document the pathoetiologic importance of thrombophilia among females presenting with severe ischemic retinal vein (RVO) or retinal artery (RAO) occlusion, without typical risk factors, and to emphasize that the ophthalmologists’ diagnosis of thrombophilia has important diagnostic and therapeutic downstream ramifications for nonocular thrombosis, including reproductive outcomes. Methods We evaluated familial and acquired thrombophilia in 60 females with RVO (central RVO, n=52; branch RVO, n=8) and 16 with RAO (central RAO, n=11; branch RAO, n=5). They were referred by retinologists, without typical risk factors for RVO/RAO and/or severe ocular ischemic presentation. We focused on extraocular thrombotic events, particularly pregnancy complications, including unexplained spontaneous abortion, pre-eclampsia–eclampsia. Thrombophilia measurements in the 76 females were compared with 62 healthy normal females without ocular vascular occlusions (OVOs). Results The 76 females with OVO were more likely than 62 normal female controls to have high homocysteine (24% vs 0%, P<0.0001), high anticardiolipin antibody (immunoglobulin M, 17% vs 3%, P=0.012), high (>150%) factor VIII (42% vs 11%, P<0.0001), and high (>150%) factor XI (22% vs 4%, P=0.004). Of the 76 females, 26 (34%) had ≥1 spontaneous abortion; 17 (22%) had ≥2 spontaneous abortions and/or pre-eclampsia–eclampsia. Compared to 62 healthy female controls, these 17 females with pregnancy complications had high homocysteine (29% vs 0%, P=0.0003), high anticardiolipin antibody immunoglobulin M (24% vs 3%, P=0.02), high factor VIII (38% vs 11%, P=0.02), and were marginally more likely to be heterozygous for the factor V Leiden mutation (19% vs 3%, P=0.058). Conclusion In females lacking typical risk factors for retinal vascular occlusion or severely ischemic presentation, by diagnosing thrombophilia as an etiology for OVO, the ophthalmologist opens a window to family screening and preventive therapy, with particular relevance to pregnancy outcomes and venous thromboembolism.
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Affiliation(s)
- Stephan G Dixon
- Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati
| | - Carl T Bruce
- Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati
| | - Charles J Glueck
- Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati
| | - Robert A Sisk
- Cincinnati Eye Institute; Department of Ophthalmology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Robert K Hutchins
- Cincinnati Eye Institute; Department of Ophthalmology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Vybhav Jetty
- Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati
| | - Ping Wang
- Cholesterol, Metabolism, and Thrombosis Center, Jewish Hospital of Cincinnati
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Venous thromboembolism does not share familial susceptibility with retinal vascular occlusion or glaucoma: a nationwide family study. J Thromb Thrombolysis 2016; 42:505-12. [DOI: 10.1007/s11239-016-1387-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Schockman S, Glueck CJ, Hutchins RK, Patel J, Shah P, Wang P. Diagnostic ramifications of ocular vascular occlusion as a first thrombotic event associated with factor V Leiden and prothrombin gene heterozygosity. Clin Ophthalmol 2015; 9:591-600. [PMID: 25897198 PMCID: PMC4396423 DOI: 10.2147/opth.s80714] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
AIM This study aimed to assess the diagnostic ramifications of vascular occlusion of the ocular vein and artery as a first thrombotic event associated with factor V Leiden (FVL) and/or prothrombin gene (PTG) heterozygosity. METHODS Patients with ocular vein (n=191) and artery (n=74) occlusion, free of cardioembolic etiologies, were sequentially referred from vitreoretinal specialists for measurement of thrombophilia-hypofibrinolysis and compared to 110 healthy normal controls. RESULTS Of the 265 patients, 29 (11%; 17 women, 12 men) of all referred ocular vascular occlusion (OVO) cases were found to be heterozygous for FVL and/or PTG, including 16 with FVL, 12 with PTG, and 1 with both. Of the 29 cases, 16 had central retinal vein occlusion (CRVO), 2 branch retinal vein occlusion (BRVO), 5 nonarteritic anterior ischemic optic neuropathy (NA-AION), 3 retinal artery occlusion (RAO), 2 amaurosis fugax (AF), and 1 had both CRVO and RAO. Of the 16 FVL cases, 15 (94%) had OVO as a first thrombotic event without prior deep venous thrombosis (DVT) or pulmonary embolism (PE); 6 (38%) also had other thrombotic events, including recurrent miscarriage, osteonecrosis, ischemic stroke, and/or ischemic colitis; and 5 (31%) had immediate family members with previous venous thromboembolism (VTE). Of the 12 PTG cases, 9 (75%) had OVO as a first thrombotic event, 5 (42%) experienced VTE other than DVT or PE, and 6 (50%) had immediate family members with VTE. In one patient with both FVL and PTG, DVT occurred before BRVO. Of the 17 women with FVL and/or PTG mutations, 7 (41%) experienced ≥1 miscarriage, 6 (35%) were on estrogen therapy, and 1 (6%) was on clomiphene. CONCLUSION Of the 265 patients with OVO, 29 (11%) had FVL and/or PTG, and 83% of these 29 cases presented with OVO as their first thrombotic event. By diagnosing thrombophilia as an etiology for OVO, the ophthalmologist opens a window to family screening and preventive therapy.
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Affiliation(s)
- Samantha Schockman
- Internal Medicine Residency Program, The Jewish Hospital-Mercy Health, Cincinnati, Ohio, USA
| | - Charles J Glueck
- Cholesterol, Metabolism, and Thrombosis Center, The Jewish Hospital-Mercy Health, Cincinnati, Ohio, USA ; Mercy Health Physicians, Mercy Health, Cincinnati, Ohio, USA
| | - Robert K Hutchins
- Department of Ophthalmology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA ; Cincinnati Eye Institute, Cincinnati, Ohio, USA
| | - Jaykumar Patel
- Cholesterol, Metabolism, and Thrombosis Center, The Jewish Hospital-Mercy Health, Cincinnati, Ohio, USA
| | - Parth Shah
- Cholesterol, Metabolism, and Thrombosis Center, The Jewish Hospital-Mercy Health, Cincinnati, Ohio, USA
| | - Ping Wang
- Cholesterol, Metabolism, and Thrombosis Center, The Jewish Hospital-Mercy Health, Cincinnati, Ohio, USA
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Abstract
A 25-year-old woman with dermatomyositis suffered a right central retinal vein occlusion (CRVO) with visual acuity of 20/40. Examination of the right eye showed vitreous cells, suggesting inflammation of the central retinal vein leading to a CRVO as the presumed mechanism. She was admitted to hospital, and extensive evaluation was negative. She was maintained on corticosteroids to manage her dermatomyositis. One month later, she had macular edema and elevated intraocular pressure. Both resolved with dorzolamide, timolol, and intravitreal bevacizumab, and vision returned to 20/20 in the right eye.
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Keren S, Loewenstein A, Coscas G. Pathogenesis, prevention, diagnosis and management of retinal vein occlusion. World J Ophthalmol 2014; 4:92-112. [DOI: 10.5318/wjo.v4.i4.92] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2014] [Revised: 08/26/2014] [Accepted: 09/17/2014] [Indexed: 02/06/2023] Open
Abstract
Retinal vein occlusion (RVO) is the second vascular retinal cause of visual loss and defined by the occlusion of a retinal vein. It is divided into branch retinal vein occlusion or central retinal vein occlusion, depending on the location of occlusion. RVO has severe medical, financial and social implications on the patients. The diagnosis of the disease is easier nowadays with the use of spectral domain optical coherence tomography and fluorescein angiography. The treatment options for RVO have changed dramatically over the past few years with the introduction of the intravitreal injections of dexamethasone (Ozurdex), bevacizumab (Avastin), ranibizumab (Lucentis) and aflibercept (EYLEA), along with the panretinal laser photocoagulation, abandoning former treatment modalities and surgical solution. This manuscript is a review of current literature about RVO with emphasize on the pathophysiology, risk factors and prevention, diagnosis and sub-group categorization and treatments including medical and surgical. Since no official guidelines are available for the treatment of RVO patients, and considering the latest developments in the treatment options, and the variety of follow-up and treatment modalities, this manuscript aims to provide tools and knowledge to guide the physician in treating RVO patients, based on the latest publications from the literature and on several of the patients characteristics.
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Martínez F, Furió E, Fabiá MJ, Pérez AV, González-Albert V, Rojo-Martínez G, Martínez-Larrad MT, Mena-Martín FJ, Soriguer F, Serrano-Ríos M, Chaves FJ, Martín-Escudero JC, Redón J, García-Fuster MJ. Risk factors associated with retinal vein occlusion. Int J Clin Pract 2014; 68:871-81. [PMID: 24548738 DOI: 10.1111/ijcp.12390] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
Abstract
AIMS Retinal vein occlusion (RVO) is the most frequent retinal vascular disease after diabetic retinopathy in which arterial risk factors are much more relevant than venous factors. The objective was to evaluate the role of risk factors in the development of the first episode of RVO. SUBJECTS AND METHODS One hundred patients with RVO [mean age 56 years, 42% females and mean body mass index (BMI) 27.5 kg/m(2)] were recruited consecutively from the outpatient clinic of a tertiary hospital in Valencia (Spain). All subjects underwent clinical assessment including anthropometric and blood pressure measurements and laboratory test including homocysteine, antiphospholipid antibodies (aPLAs) and thrombophilia studies. In half of the subjects, a carotid ultrasonography was performed. Three control populations matched by age, sex and BMI from different population-based studies were used to compare the levels and prevalence of arterial risk factors. One cohort of young patients with venous thromboembolic disease was used to compare the venous risk factors. RESULTS Blood pressure levels and the prevalence of hypertension were significantly higher in the RVO population when compared with those for the general populations. There was also a large proportion of undiagnosed hypertension within the RVO group. Moreover, carotid evaluation revealed that a large proportion of patients with RVO had evidence of subclinical organ damage. In addition, homocysteine levels and prevalence of aPLAs were similar to the results obtained in our cohort of venous thromboembolic disease. CONCLUSIONS The results indicate that hypertension is the key factor in the development of RVO, and that RVO can be the first manifestation of an undiagnosed hypertension. Furthermore, the majority of these patients had evidence of atherosclerotic disease. Among the venous factors, a thrombophilia study does not seem to be useful and only the prevalence of hyperhomocysteinaemia and aPLAs is higher than in the general population.
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Affiliation(s)
- F Martínez
- Internal Medicine Department, Fundación de Investigación del Hospital Clínico de Valencia- INCLIVA, Hospital Clínico Universitario, Universidad de Valencia, Valencia, Spain; "Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología, Obesidad y Nutrición (CIBEROB)", Institute of Health Carlos III, Minister of Health, Madrid, Spain
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Russo PD, Damante G, Pasca S, Turello M, Barillari G. Thrombophilic Mutations as Risk Factor for Retinal Vein Occlusion. Clin Appl Thromb Hemost 2014; 21:373-7. [DOI: 10.1177/1076029614522544] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Retinal vein occlusion (RVO) is the second most common retinal vein disease and an important cause of blindness and visual morbidity. Many conditions are associated with RVO but the real role of the thrombophilic mutations is still unclear. Aim: To evaluate the potential role of thrombophilic mutations in RVO. Methods: We have evaluated 113 patients with RVO and compared with 104 volunteer controls. The controls were all healthy blood donors without previous venous thromboembolism episode or arterial thromboembolism episode. All patients were tested for 5 gene variants (here all named as mutations): factor V ( FV) Leiden (G1691A), factor II ( FII; G20210A), 5,1-methylenetetra-hydrofolate reductase ( MTHFR; C677T), plasminogen activator inhibitor 1 ( PAI-1; 4G/5G), and angiotensin-converting enzyme ( ACE; Del/Ins). Statistical analysis were performed by the 2-tailed chi-square test. Results: Statistical test showed that TT homozygous patients of the MTHFR C677T mutation ( P = .017) and heterozygous GA patients of the FII G20210A mutation ( P = .018) were significantly higher than that in controls. For FV Leiden, even if the values were higher in patients than in controls, P value was not statistically significant. Conversely, for the ACE (Ins/Del) and PAI-1 (4G/5G) mutations, no difference was observed among genotypes of patients with RVO and control participants. Conclusions: In our study, the FII G20210A and the MTHFR C677T mutations resulted significantly higher in patients than in controls; in contrast, thrombophilic mutation of FV, ACE, and PAI-1 genes was not statistically correlated with RVO. In spite of having found an association between some thrombophilic mutations and RVO, more studies with a major number of patients are necessary to determine the final role of these gene variants.
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Affiliation(s)
| | - Giuseppe Damante
- Department of Medical, Biological Sciences of Udine University, Institute of Medical Genetics, University Hospital of Udine, Udine, Italy
| | - Samantha Pasca
- Center for Hemorrhagic and Thrombotic Diseases, University Hospital of Udine, Udine, Italy
| | - Marina Turello
- Center for Hemorrhagic and Thrombotic Diseases, University Hospital of Udine, Udine, Italy
| | - Giovanni Barillari
- Center for Hemorrhagic and Thrombotic Diseases, University Hospital of Udine, Udine, Italy
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Bertelsen M, Linneberg A, Christoffersen N, Vorum H, Gade E, Larsen M. Mortality in patients with central retinal vein occlusion. Ophthalmology 2013; 121:637-42. [PMID: 24053999 DOI: 10.1016/j.ophtha.2013.07.025] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2013] [Revised: 07/16/2013] [Accepted: 07/18/2013] [Indexed: 11/17/2022] Open
Abstract
PURPOSE To assess mortality in patients with central retinal vein occlusion (CRVO). DESIGN Registry-based cohort study. PARTICIPANTS AND CONTROLS Four hundred thirty-nine photographically verified CRVO patients and a control cohort of 2195 unexposed subjects matched by age and gender and alive on the date CRVO was diagnosed in the corresponding case. METHODS Data from nationwide registries were used to compare mortality rates in CRVO patients with a control cohort over a mean follow-up of 5.1 years for cases and of 5.7 years for controls. MAIN OUTCOME MEASURES Hazard ratios (HRs) obtained by Cox regression and standardized mortality ratios (SMRs) stratified by age and gender served as measures of relative mortality risk. RESULTS Mortality was higher in patients with CRVO (HR, 1.45; 95% confidence interval [CI], 1.19-1.76) than in the control cohort, adjusted for age, gender, and time of diagnosis. Mortality was comparable between the 2 groups (HR, 1.19; 95% CI, 0.96-1.46) when adjusting for overall occurrence of cardiovascular disease and diabetes. Subgroup analysis found that the age-stratified mortality rate was increased significantly in the total group of men (SMR, 1.27; 95% CI, 1.03-1.56) and in women 60 to 69 years of age (SMR, 1.94; 95% CI, 1.22-3.08). CONCLUSIONS Central retinal vein occlusion was associated with an overall increase in mortality compared with controls that was attributed statistically to cardiovascular disorders and diabetes. We recommend treatment of hypertension and diabetes, if present, and referral of patients found to have CRVO who are not already being treated by a primary care physician.
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Affiliation(s)
- Mette Bertelsen
- National Eye Clinic for the Visually Impaired, Kennedy Center, Glostrup, Denmark; Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
| | - Allan Linneberg
- Research Centre for Prevention and Health, Copenhagen University Hospital, Glostrup, Denmark
| | - Nynne Christoffersen
- National Eye Clinic for the Visually Impaired, Kennedy Center, Glostrup, Denmark
| | - Henrik Vorum
- Department of Ophthalmology, Aalborg University Hospital, Aalborg, Denmark
| | - Else Gade
- Department of Ophthalmology, Odense University Hospital, Odense, Denmark
| | - Michael Larsen
- Department of Ophthalmology, Glostrup Hospital, Glostrup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Shahsuvaryan ML. Therapeutic potential of intravitreal pharmacotherapy in retinal vein occlusion. Int J Ophthalmol 2012; 5:759-70. [PMID: 23275914 PMCID: PMC3530822 DOI: 10.3980/j.issn.2222-3959.2012.06.20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2012] [Accepted: 11/19/2012] [Indexed: 11/02/2022] Open
Abstract
Retinal vein occlusion (RVO) is the most common visually disabling disease affecting the retina after diabetic retinopathy. Although the disease entity has long been known, its management is still controversial. Macular edema is the main reason for decreased visual acuity (VA) in this retinal vascular disorder. Recently the vitreous cavity has increasingly been used as a reservoir of drugs for the direct treatment of macular edema through intravitreal injection route. The most widely injected drugs so far have been triamcinolone acetonide (TA) and bevacizumab. The objective of this review is to evaluate the evidence and discuss the rationale behind the recent suggestions that intravitreal pharmacotherapy by corticosteroids and anti-vascular endothelial growth factors may be useful in the treatment of retinal vein occlusion.
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Stem MS, Talwar N, Comer GM, Stein JD. A longitudinal analysis of risk factors associated with central retinal vein occlusion. Ophthalmology 2012. [PMID: 23177364 DOI: 10.1016/j.ophtha.2012.07.080] [Citation(s) in RCA: 79] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
PURPOSE To identify risk factors associated with central retinal vein occlusion (CRVO) among a diverse group of patients throughout the United States. DESIGN Longitudinal cohort study. PARTICIPANTS All beneficiaries aged ≥ 55 years who were continuously enrolled in a managed care network for at least 2 years and who had ≥ 2 visits to an eye care provider from 2001 to 2009. METHODS Insurance billing codes were used to identify individuals with a newly diagnosed CRVO. Multivariable Cox regression was performed to determine the factors associated with CRVO development. MAIN OUTCOME MEASURES Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of being diagnosed with CRVO. RESULTS Of the 494 165 enrollees who met the study inclusion criteria, 1302 (0.26%) were diagnosed with CRVO over 5.4 (± 1.8) years. After adjustment for known confounders, blacks had a 58% increased risk of CRVO compared with whites (HR, 1.58; 95% CI, 1.25-1.99), and women had a 25% decreased risk of CRVO compared with men (HR, 0.75; 95% CI, 0.66-0.85). A diagnosis of stroke increased the hazard of CRVO by 44% (HR, 1.44; 95% CI, 1.23-1.68), and hypercoagulable state was associated with a 145% increased CRVO risk (HR, 2.45; 95% CI, 1.40-4.28). Individuals with end-organ damage from hypertension (HTN) or diabetes mellitus (DM) had a 92% (HR, 1.92; 95% CI, 1.52-2.42) and 53% (HR, 1.53; 95% CI, 1.28-1.84) increased risk of CRVO, respectively, relative to those without these conditions. CONCLUSIONS This study confirms that HTN and vascular diseases are important risk factors for CRVO. We also identify black race as being associated with CRVO, which was not well appreciated previously. Furthermore, we show that compared with patients without DM, individuals with end-organ damage from DM have a heightened risk of CRVO, whereas those with uncomplicated DM are not at increased risk of CRVO. This finding may provide a potential explanation for the conflicting reports in the literature on the association between CRVO and DM. Information from analyses such as this can be used to create a risk calculator to identify possible individuals at greatest risk for CRVO.
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Affiliation(s)
- Maxwell S Stem
- Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, Michigan, USA
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Fusconi M, Chistolini A, de Virgilio A, Greco A, Massaro F, Turchetta R, Benincasa AT, Tombolini M, de Vincentiis M. Sudden sensorineural hearing loss: a vascular cause? Analysis of prothrombotic risk factors in head and neck. Int J Audiol 2012; 51:800-5. [PMID: 22928918 DOI: 10.3109/14992027.2012.705904] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
OBJECTIVE This aim of this study was to determine the prevalence of thrombophilic risk factors in sudden sensorineural hearing loss, central retinal vein occlusion, and stroke associated with small vessel disease, with the purpose of investigating and reinforcing the vascular hypothesis in the pathogenesis of sudden sensorineural hearing loss. DESIGN Case-control study. Genetic and acquired risk factors of these three groups were compared with healthy controls. STUDY SAMPLE Forty-nine, 60, and 101 patients affected respectively by sudden sensorineural hearing loss, central retinal vein occlusion, or stroke associated with small vessel disease, enrolled during a three-year period were compared with 210 healthy controls. RESULTS The frequency of hyperhomocysteinemia (homocysteine ≥ 15 μmol/L) was higher in each disease group than in controls. A statically significant, albeit weak, correlation between the MTHFR C677T mutation and hyperhomocysteinemia was found in all three diseases. CONCLUSIONS Hyperhomocysteinemia proved to be a risk factor for sudden sensorineural hearing loss. Based on these results, we propose to analyse homocysteine in sudden sensorineural hearing loss patients and, if its values are high, to evaluate the presence of MTHFR C677T mutation.
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Affiliation(s)
- Massimo Fusconi
- Department of Sensory Organs, Sapienza University of Rome, Italy.
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Coscas G, Loewenstein A, Augustin A, Bandello F, Battaglia Parodi M, Lanzetta P, Monés J, de Smet M, Soubrane G, Staurenghi G. Management of retinal vein occlusion--consensus document. ACTA ACUST UNITED AC 2011; 226:4-28. [PMID: 21577038 DOI: 10.1159/000327391] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Retinal vein occlusion (RVO) can have severe consequences for the people affected by the disease, including visual loss with costly social repercussions. Currently, there is no European consensus with regard to the management of RVO. Following a careful review of the medical literature as well as the data from several clinical trials, a collaborative group of retina specialists put forth practical recommendations based on the best available scientific evidence for the clinical approach to RVO. Taking into consideration the recent advances in diagnostic tools and management options, the present document aims to provide the European ophthalmologists with guidelines for clinical practice to the benefit of their patients.
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Affiliation(s)
- Gabriel Coscas
- Hôpital Intercommunal de Créteil, Service Universitaire d'Ophtalmologie, Créteil, France.
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Wang HY, Li X, Wang YS, Zhang ZF, Li MH, Su XN, Zhu JT. Intravitreal injection of bevacizumab alone or with triamcinolone acetonide for treatment of macular edema caused by central retinal vein occlusion. Int J Ophthalmol 2011; 4:89-94. [PMID: 22553618 DOI: 10.3980/j.issn.2222-3959.2011.01.21] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Accepted: 12/28/2010] [Indexed: 11/02/2022] Open
Abstract
AIM To compare the efficacy and safety of intravitreal bevacizumab alone versus bevacizumab combined with triamcinolone acetonide in eyes with macular edema caused by central retinal vein occlusion (CRVO) in Chinese patients. METHODS Seventy-five eyes of 75 patients were enrolled in this prospective, randomized, consecutive study. Thirty-six patients in group 1 were treated with an intravitreal injection of bevacizumab (1.25mg/0.05mL), and 39 patients in group 2 were treated with intravitreal bevacizumab (1.25mg/0.05mL) combined with triamcinolone acetonide (2mg/0.05mL). The main outcomes of the mean best corrected visual acuity (BCVA), central retinal thickness (CRT), and intraocular pressure (IOP) were measured. RESULTS In group 1, the mean BCVA improved from 37.78±6.14 (baseline) to 48.06±3.86, 46.48±4.77 and 44.18±5.78 at four, six and twelve weeks post-injection, respectively (P<0.01, P=0.03, P=0.04). In group 2, the mean BCVA improved from 35.92±6.20 (baseline) to 50.69±4.22, 48.76±5.59 and 45.70±6.56 at the same time points (P<0.01 each). However, there was no significant differences in the mean BCVA (F=0.043, P=0.836) and CRT (F=0.374, P=0.544) between these two groups. During the follow-up, five patients in group 1 and six patients in group 2 with high IOP were controlled with anti-glaucoma drugs. CONCLUSION Intravitreal injection of bevacizumab alone or combined with triamcinolone acetonide has a short beneficial effect in Chinese patients with macular edema caused by CRVO, but there is no significant difference between the two groups.
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Affiliation(s)
- Hai-Yan Wang
- Department of Ophthalmology, The Eye Institute of PLA, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China
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Karia N. Retinal vein occlusion: pathophysiology and treatment options. Clin Ophthalmol 2010; 4:809-16. [PMID: 20689798 PMCID: PMC2915868 DOI: 10.2147/opth.s7631] [Citation(s) in RCA: 98] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2010] [Indexed: 11/23/2022] Open
Abstract
This paper reviews the current thinking about retinal vein occlusion. It gives an overview of its pathophysiology and discusses the evidence behind the various established and emerging treatment paradigms.
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Affiliation(s)
- Niral Karia
- Department of Ophthalmology, Southend Hospital, Prittlewell Chase, Westcliff on Sea, Essex, United Kingdom.
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29
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Parnaparin versus aspirin in the treatment of retinal vein occlusion. A randomized, double blind, controlled study. Thromb Res 2010; 125:137-41. [DOI: 10.1016/j.thromres.2009.05.007] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2009] [Revised: 05/05/2009] [Accepted: 05/06/2009] [Indexed: 11/20/2022]
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Ates O, Keles M, Uyanik A, Bilen H, Cetinkaya R, Turkeli M. Central retinal vein thrombosis and hyperhomocysteinemia in a young patient with renal transplantation. Transplant Proc 2008; 40:3755-8. [PMID: 19100482 DOI: 10.1016/j.transproceed.2008.03.166] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2007] [Revised: 02/11/2008] [Accepted: 03/26/2008] [Indexed: 11/26/2022]
Abstract
A 28-year-old woman was admitted with a sudden loss of vision in the right eye. She underwent renal transplantation in June 1999 for chronic renal failure secondary to amyloidosis. Upon ophthalmologic examination, the patient was diagnosed with central retinal vein occlusion. Physical and laboratory examinations failed to disclose any remarkable pathology except for high homocysteine levels. Hyperhomocysteinemia has been reported as a potential risk factor requiring treatment and a significant association has been found between this condition and central retinal vein thrombosis.
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Affiliation(s)
- O Ates
- Department of Internal Medicine, School of Medicine, University of Atatürk, Yakutiye, Erzurum, Turkey
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Sodi A, Giambene B, Marcucci R, Sofi F, Bolli P, Abbate R, Prisco D, Menchini U. Atherosclerotic and thrombophilic risk factors in patients with recurrent central retinal vein occlusion. Eur J Ophthalmol 2008; 18:233-8. [PMID: 18320516 DOI: 10.1177/112067210801800211] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE Atherosclerotic and thrombophilic risk factors may be causes of central retinal vein occlusion (CRVO). The aim of this study was to evaluate the prevalence of the aforesaid risk factors in patients with recurrent CRVOs and patients with a single episode of CRVO. METHODS Seventeen patients with recurrent CRVO and 30 with a single episode of CRVO were enrolled. The atherosclerotic risk factors investigated were hypertension, diabetes, smoking, and dyslipidemia. Specific laboratory tests for the following thrombophilic markers were performed: homocystinemia (Hcy), lipoprotein (a), factor VIII, factor II G20210A and factor V G1691A polymorphisms, lupus anticoagulant, anticardiolipin antibodies, plasminogen activator inhibitor-1, and deficit of vitamins B6, B12, and folic acid. A multivariate analysis, adjusted for age, gender, traditional and thrombophilic risk factors, was performed. Statistical significance was set at p<or=0.05. RESULTS Hypercholesterolemia, hypertriglyceridemia, fasting, and postmethionine hyperhomocysteinemia (HHcy) were more prevalent in recurrent CRVO patients (p<0.001, p<0.001, p=0.006, and p=0.005, respectively). At multivariate analysis, hypercholesterolemia (OR: 5.04, 95% CI 1.39-18.17; p=0.025), hypertriglyceridemia (OR: 5.60, 95% CI 1.52-20.61; p=0.017), fasting HHcy (OR: 5.77, 95% CI 1.39-23.89; p=0.028), and postmethionine HHcy (OR: 10.88, 95% CI 2.50-47.42; p=0.002) were found to be significantly associated with recurrent CRVO. CONCLUSIONS Dyslipidemia and hyperhomocysteinemia are independent risk factors for the occurrence of recurrent CRVO. A complete assessment of atherosclerotic and thrombophilic risk factors in CRVO patients. In addition, the need for a specific treatment is suggested.
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Affiliation(s)
- A Sodi
- Department of Oto-Neuro-Ophthalmological Surgical Sciences, Eye Clinic, Firenze, Italy
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Mirshahi A, Feltgen N, Hansen LL, Hattenbach LO. Retinal vascular occlusions: an interdisciplinary challenge. DEUTSCHES ARZTEBLATT INTERNATIONAL 2008; 105:474-9. [PMID: 19626196 PMCID: PMC2696914 DOI: 10.3238/arztebl.2008.0474] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/19/2007] [Accepted: 01/03/2008] [Indexed: 11/27/2022]
Abstract
INTRODUCTION Retinal venous and arterial occlusions are common causes of visual loss. Depending on the location and extent, symptoms may vary from very discrete impairments to complete loss of sight. METHODS Selective literature review including the authors' own research data with a particular focus on interdisciplinary aspects. RESULTS Retinal vascular occlusions are not a uniform entity. Rather, they reflect the whole breadth of vascular disease. In arterial occlusion, embolic phenomena and Horton's arteritis should be excluded, in addition to local ophthalmological investigations. In retinal venous occlusion, optimal treatment of arterial hypertension is universally useful, while investigations for thrombophilia are useful in patients under 50 years of age. The results of intravitreal injection of corticosteroids and vascular endothelial growth factor inhibitors appear encouraging in treatment of macular edema secondary to retinal vein occlusion. DISCUSSION While local diagnostic and therapeutic measures are performed by ophthalmologists, there is an important role for interdisciplinary cooperation in the investigation and systemic treatment of these events.
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Affiliation(s)
- Alireza Mirshahi
- Klinikum Ludwigshafen, Augenklinik, Bremserstrasse 79, Ludwigshafen, Germany.
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Central Retinal Vein Occlusion Secondary to Protein S Deficiency. ACTA ACUST UNITED AC 2007; 39:343-4. [DOI: 10.1007/s12009-007-9004-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2007] [Revised: 11/30/1999] [Accepted: 06/29/2007] [Indexed: 11/26/2022]
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Garcia-Arumi J, Boixadera A, Martinez-Castillo V, Montolio M, Verdugo A, Corcóstegui B. Radial optic neurotomy in central retinal vein occlusion: comparison of outcome in younger vs older patients. Am J Ophthalmol 2007; 143:134-140. [PMID: 17113557 DOI: 10.1016/j.ajo.2006.08.034] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2005] [Revised: 08/02/2006] [Accepted: 08/21/2006] [Indexed: 11/28/2022]
Abstract
PURPOSE To evaluate the effectiveness of radial optic neurotomy (RON) for central retinal vein occlusion (CRVO) in patients < or =50 years of age (group 1) vs those >50 (group 2). DESIGN Prospective, interventional, comparative case series. METHODS The study included 43 consecutive patients with CRVO and preoperative visual acuity (VA) < or =0.70 logarithm of minimal angle of resolution (logMAR). All patients underwent pars plana vitrectomy and RON at the nasal border of the optic disk. VA and optical coherence tomography (OCT) findings were recorded preoperatively and at one, six, and 12 months postoperatively. RESULTS Systemic hypertension, diabetes, and open-angle glaucoma were statistically significantly more prevalent in group 2 (P < .05). One patient in group 1 had hyperhomocysteinemia, and had another antiphospholipid syndrome. Fifty percent of patients in group 1 gained > or =3 lines of Early Treatment Diabetic Retinopathy Study (ETDRS) vision, vs 33% in group 2. Mean final VA was 0.5 logMAR VA in group 1 vs 0.8 in group 2 (P = .04). Foveal thickness decreased significantly in both groups (P < .001). Ten patients (55.6%) in group 1 and 13 (54.2%) in group 2 developed retinochoroidal collaterals. CONCLUSIONS Underlying systemic disease does not seem to be an important factor in the pathogenesis of CRVO in younger patients, and thrombophilia was present in only 11% of patients in this age group. RON yielded better functional results in younger patients, although functional improvement remained limited in those with low baseline VA.
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Affiliation(s)
- Jose Garcia-Arumi
- Hospital Vall d'Hebrón, Universidad Autónoma de Barcelona, 08022 Barcelona, Spain.
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Paccalin M, Manic H, Bouche G, Landron C, Mercié M, Boinot C, Gombert JM, Roblot P, Dighiero P. Antiphospholipid syndrome in patients with retinal venous occlusion. Thromb Res 2006; 117:365-9. [PMID: 16461072 DOI: 10.1016/j.thromres.2005.03.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2005] [Revised: 03/29/2005] [Accepted: 03/30/2005] [Indexed: 11/20/2022]
Abstract
INTRODUCTION We conducted a prospective study to determine the prevalence and the prognosis of antiphospholipid syndrome (APS) in patients with retinal venous occlusion (RVO). PATIENTS Consecutive patients presenting with retinal vein occlusion were screened for vascular risk factors (diabetes mellitus, hypertension, hyperlipidemia) and for antiphospholipid antibodies (aPL): anticardiolipin (aCL), anti-beta2-glycoprotein I, and lupus anticoagulant. Patients with a serum sample positive for aPL returned at least 6 weeks later for a new screening to determine the prevalence of antiphospholipid syndrome. All patients were followed to determine the outcome. RESULTS Sixty-eight patients presented with RVO, 16 had vascular risk factors for RVO. After two screenings for aPL, nine cases of antiphospholipid syndrome associated with RVO were diagnosed (13.2%). Eight patients were over age 50 years and none had a previous thrombotic event before RVO. All patients were treated with aspirin (160 mg/day). With a mean follow-up of 26.1+/-8.2 months (range, 16-36 months), there were no recurrences. CONCLUSION Retinal venous occlusion is multifactorial in origin. In patients aged 50 years and older, without previous thrombotic event, aPL might not be predictive of recurrences and treatment with aspirin might be sufficient. In such patients, the routine screening for aPL does not appear warranted, but a randomized study should be conducted to really ascertain the pathogenic role of aPL and the most appropriate treatment in RVO.
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Affiliation(s)
- M Paccalin
- Department of Internal Medicine, University hospital La Milétrie, Poitiers, France.
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Koren-Michowitz M, Eting E, Rahimi-Levene N, Garach-Jehoshua O, Volcheck Y, Kornberg A. Protein Z levels and central retinal vein or artery occlusion. Eur J Haematol 2005; 75:401-5. [PMID: 16191090 DOI: 10.1111/j.1600-0609.2005.00529.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
OBJECTIVES Central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO) are common disorders associated with risk factors for atherosclerosis. Protein Z is a cofactor for the inactivation of activated factor X (Xa) by the protein Z dependent protease inhibitor. Protein Z deficiency was recently linked to increased risk of arterial thrombosis. We investigated whether CRVO and CRAO are associated with low protein Z levels. PATIENTS AND METHODS Patients with CRVO, CRAO or recurrent branch retinal vein occlusion were recruited to the study. Protein Z level, lupus anticoagulant (LAC), anticardiolipin antibodies (ACA) and activated protein C resistance (APCR) were determined in plasma from patients (n = 36) and healthy controls (n = 42). RESULTS Thirty patients in the study group had traditional risk factors for retinal vessel occlusion and six patients had none. There was no significant difference in protein Z levels between the whole study group patients and controls (1995 +/- 810 vs. 2010 +/- 603 ng/mL, P = 0.922). However, patients with no risk factors for retinal vessel occlusion had significantly lower protein Z levels than controls (1379 +/- 682 vs. 2010 +/- 603 ng/mL, P = 0.022). Positive LAC was found in six patients and one control subject (P = 0.04). There were three patients and one control subject with abnormal APCR (P = 0.3) and none with positive ACA. Low protein Z level (lower than fifth percentile of control) was not associated with the presence of LAC or APCR. CONCLUSION Low protein Z level may be another risk factor for retinal vessel occlusion in patients without traditional risk factors for these disorders.
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Banik S, Bhutto HU, Bagga P. Recurrent branch retinal vein occlusion with factor V leiden mutation. Eye (Lond) 2005; 20:948-9. [PMID: 16113634 DOI: 10.1038/sj.eye.6702060] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
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Nagy V, Steiber Z, Takacs L, Vereb G, Berta A, Bereczky Z, Pfliegler G. Trombophilic screening for nonarteritic anterior ischemic optic neuropathy. Graefes Arch Clin Exp Ophthalmol 2005; 244:3-8. [PMID: 15834600 DOI: 10.1007/s00417-005-1154-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2004] [Revised: 01/11/2005] [Accepted: 01/22/2005] [Indexed: 10/25/2022] Open
Abstract
BACKGROUND Nonarteritic anterior ischemic optic neuropathy (NAION) is an ischemic infarction of the optic nerve head, frequently leading to sudden, mostly irreversible loss of vision. In this study blood thrombophilic factors, as well as cardiovascular risk factors were investigated for their relevance to this pathology. Trombophilic risk factors so far not evaluated were included in the study. PATIENTS AND METHODS 37 NAION patients (4 with sequential second eye involvement) and 81 matched control subjects were examined. From blood, protein C, protein S, antithrombin, von Willebrand antigen levels (vWFAg), and factor V (Leiden) mutation, factor VIIIC level, plasminogen activity, lipoprotein (a) and fibrinogen levels, and presence of anticardiolipin antibodies were investigated. Possibly relevant pathologies [e.g. diabetes mellitus (DM), hypertension, and ischemic heart disease] were also registered. RESULTS Elevated Lp(a) and vWFAg levels, DM, F V (Leiden), hypercholesterolemia, and hyperfibinogenemia proved to be significant risk factors associated with NAION. Forward stepwise logistic regression analysis revealed that high Lp(a), DM, and FV (Leiden) were the main predictive components, with odds ratios 16.88 (p=0.012), 5.78 (p=0.022) and 4.44 (p=0.033), respectively. CONCLUSIONS Based on our results it appears that thrombophilia is likely to contribute to the development of NAION besides vascular damage due to the presence of cardiovascular risk factors. Further data are needed, however, to justify the suggested use of secondary prophylaxis using anticoagulant/antiplatelet therapy.
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Affiliation(s)
- Valeria Nagy
- Department of Ophthalmology, University of Debrecen, Medical and Health Science Center, 4012 Debrecen, Hungary.
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Holak HM, Holak NH, Holak S, Holak SA, Szymaniec S. Venenastverschluss und Abduzensparese bei Protein-S-Mangel. Ophthalmologe 2005; 102:279-85. [PMID: 15138794 DOI: 10.1007/s00347-004-1032-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND Protein S deficiency, which exists in 0.7% of the population, is a risk factor for retinal vein branch occlusions and is inherited in an autosomal dominant manner. METHODS A genealogical study was carried out on three generations of one family who exhibited different venous occlusions and subsequent complications. RESULTS Four members of the family, spanning three generations, suffered from complications of venous thrombosis. In the first generation a great uncle died of complications from a deep leg venous thrombosis. In the second generation, the mother underwent a venous branch thrombosis at the age of 41 with a protein S activity of 18%. Subsequently, a palsy of the N. abducens developed with multiple cerebral lesions (presumably post-thrombotic) in the MRI. Fluorescein angiography showed a typical picture of a venous branch occlusion which had been treated by laser. In the third generation, the 16-year-old daughter developed iliac venous thrombosis and a pulmonary embolism with a protein S activity of 0%. The fluorescein angiography showed distinctively engorged veins. A 28-year-old daughter, with a protein S activity of 16%, remained asymptomatic, although fluorescein angiography demonstrated engorged veins. Protein C activity and APC resistance of all family members were normal. The chromosomal analysis of the family members revealed no morphological aberrations. CONCLUSION Protein S deficiency increases the risk of congenital thrombosis in young and middle-aged heterozygous individuals.
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Affiliation(s)
- H M Holak
- Gemeinschaftspraxis der Augenärzte im Rudolf-Virchow-Arztehaus, Salzgitter
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Abstract
The genetic thrombophilias are an important cause of venous thrombotic events. Much has been learned about the natural history of these disorders, their genetics, and, to a lesser degree, their treatment. This article provides an overview of the genetics of thrombophilia. Specific information on the factor V Leiden mutation;the prothrombin G20210A mutation; and protein C, proteinS, and antithrombin deficiency is reviewed. Current testing and treatment options for the genetic thrombophilias also are discussed.
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Affiliation(s)
- W Gregory Feero
- Department of Community and Family Medicine, Dartmouth Medical School, Hanover, NH, 03755, USA.
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Abu El-Asrar AM, Al-Obeidan SA, Abdel Gader AGM. Retinal periphlebitis resembling frosted branch angiitis with nonperfused central retinal vein occlusion. Eur J Ophthalmol 2004; 13:807-12. [PMID: 14700106 DOI: 10.1177/1120672103013009-1015] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE To report the unusual association between severe retinal periphlebitis resembling frosted branch angiitis and nonperfused central retinal vein occlusion (CRVO). METHODS Observational case reports. RESULTS Patient 1 was a 28-year-old man who presented with extensive sheathing involving all retinal veins in one eye followed by nonperfused CRVO. Twenty-seven months after initial presentation, he developed perfused CRVO in the other eye followed by periphlebitis that progressed into nonperfused CRVO. Patient 2 was a 47-year-old man who presented with unilateral severe retinal periphlebitis associated with nonperfused CRVO. Despite systemic administration of corticosteroid therapy, rubeosis iridis developed in both patients and neovascular glaucoma developed in Patient 1 despite full panretinal photocoagulation. Extensive systemic workup and coagulation studies were unremarkable except for the presence of antiphospholipid antibodies in both patients and elevated plasma homocysteine level in Patient 2. CONCLUSIONS Severe retinal periphlebitis complicated by nonperfused CRVO is associated with poor visual outcome despite appropriate medical and surgical treatment.
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Affiliation(s)
- A M Abu El-Asrar
- Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
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Dewerchin M, Hérault JP, Wallays G, Petitou M, Schaeffer P, Millet L, Weitz JI, Moons L, Collen D, Carmeliet P, Herbert JM. Life-threatening thrombosis in mice with targeted Arg48-to-Cys mutation of the heparin-binding domain of antithrombin. Circ Res 2003; 93:1120-6. [PMID: 14592998 DOI: 10.1161/01.res.0000103634.69868.4f] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Antithrombin (AT) inhibits thrombin and some other coagulation factors in a reaction that is dramatically accelerated by binding of a pentasaccharide sequence present in heparin/heparan-sulfate to a heparin-binding site on AT. Based on the involvement of R47 in the heparin/AT interaction and the frequent occurrence of R47 mutations in AT deficiency patients, targeted knock-in of the corresponding R48C substitution in AT in mice was performed to generate a murine model of spontaneous thrombosis. The mutation efficiently abolished the effect of heparin-like molecules on coagulation inhibition in vitro and in vivo. Mice homozygous for the mutation (AT(m/m) mice) developed spontaneous, life-threatening thrombosis, occurring as early as the day of birth. Only 60% of the AT(m/m) offspring reached weaning age, with further loss at different ages. Thrombotic events in adult homozygotes were most prominent in the heart, liver, and in ocular, placental, and penile vessels. In the neonate, spontaneous death invariably was associated with major thrombosis in the heart. This severe thrombotic phenotype underlines a critical function of the heparin-binding site of antithrombin and its interaction with heparin/heparan-sulfate moieties in health, reproduction, and survival, and represents an in vivo model for comparative analysis of heparin-derived and other antithrombotic molecules.
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Affiliation(s)
- Mieke Dewerchin
- Center for Transgene Technology and Gene Therapy, VIB, KULeuven Campus Gasthuisberg O&N, Herestraat 49, B-3000 Leuven, Belgium.
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Abstract
Central retinal vein occlusion is a common cause of permanent visual loss. Work up and laboratory evaluation of patients requires the clinician to rule out hypertension, diabetes, hyperlipidemia, and glaucoma. Patients without an identifiable risk factor are often subject to extensive testing for primary and secondary thrombophilias. The purpose this paper is to review the literature to determine which of these tests is associated with central retinal vein occlusion. Antiphospholipid antibodies and elevated plasma homocysteine levels appear to be the tests associated most commonly in patients with central retinal vein occlusion in most controlled studies. Primary thrombophilias are found rarely when screening patients with central retinal vein occlusion. Extensive testing for thrombophilias is not warranted in the vast majority of patients with central retinal vein occlusion. Older patients with any of the common vascular risk factors do not require thrombophilic screening. By carefully selecting the patients who are evaluated for thrombophilias, the likelihood of finding true-positive tests is increased.
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Affiliation(s)
- J Michael Lahey
- Permanente Medical Group, Hayward, California, Department of Ophthalmology, Retinal Division, Union City, CA 94587, USA.
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45
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Dodson PM, Haynes J, Starczynski J, Farmer J, Shigdar S, Fegan G, Johnson RJ, Fegan C. The platelet glycoprotein Ia/IIa gene polymorphism C807T/G873A: a novel risk factor for retinal vein occlusion. Eye (Lond) 2003; 17:772-7. [PMID: 12928694 DOI: 10.1038/sj.eye.6700452] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Retinal vein occlusion (RVO) is associated with hyperhomocysteinaemia and the antiphospholipid syndrome-disorders known to contribute to both arterial and venous thrombosis. In both of these conditions and RVO, platelet activation occurs. Aspirin, not warfarin, is the most effective antithrombotic agent in RVO and, taken together, these observations suggest an important role for platelets in this common ocular thrombotic condition. Platelet glycoprotein Ia/IIa (GpIa/IIa) is an adhesion molecule mediating platelet-collagen interactions and is key to the initiation of thrombosis. Recently, the cellular density of this molecule was shown to be determined by two silent, linked polymorphisms (C807T/G873A) within the GpIa/IIa gene. There is evidence that some of the resulting genotypes are associated with thrombo-embolic disease. This study therefore aimed to establish the prevalence of the GpIa/IIa polymorphisms and the three commonest hereditary thrombophilic disorders (prothrombin gene G20210A (PT) mutation, Factor V Leiden (FVL), and the thermolabile methylene tetrahydrofolate reductase C677T (MTHFR) mutation) in patients with RVO and normal controls. The GpIa/IIa polymorphisms and thrombophilic abnormalities were all identified using the polymerase chain reaction.Our results show that the frequency of the GpIa/IIa polymorphisms was similar in our normal control population to previously published series. Patients with RVO, however, had only a 10% (4/40) frequency of the lowest risk subtype (CC/GG) compared to 37.5% (15/40) in the control group-P 0.0039. The incidence of the PT, FVL, and MTHFR thrombophilic mutations was not different between the two groups, but interestingly none of the 7/40 RVO cases with a PT, FVL, or MTHFR mutation had the low-risk GpIa/IIa genotype while all but one of the controls did-P<0.05. Thus, 17.5% of RVO patients harboured more than one prothrombotic abnormality. The principal difference between the RVO and control group was the very high incidence of the intermediate-risk GpIa/IIa subtype (CT/GA)-82.5 vs 50%, P&<0.05. These results suggest a major role for GpIa/IIa polymorphisms in the pathogenesis of RVO.
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Affiliation(s)
- P M Dodson
- Department of Medical Ophthalmology Heartlands Hospital Bordesley Green East Birmingham B9 5SS, UK
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Shahsuvaryan ML, Melkonyan AK. Central retinal vein occlusion risk profile: a case-control study. Eur J Ophthalmol 2003; 13:445-52. [PMID: 12841567 DOI: 10.1177/112067210301300505] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
PURPOSE To identify risk factors for central retinal vein occlusion (CRVO). METHODS This clinic-based case-control study included 408 patients with CRVO aged 21 years and older and 566 controls who were seen between January 1, 1990, and December 31, 2001. Multivariate logistic regression analysis was used to adjust for various factors and test potential interactions between the different variables. RESULTS An increased risk of CRVO was found in persons with systemic hypertension, but odds ratios were greater for older patients. Risk of CRVO increases with age and also in association with hypercoagulability. Diabetes mellitus, kidney disease, and glaucoma were associated with increased risk for CRVO. A significantly greater prevalence of higher erythrocyte sedimentation rate was present in young adults compared with older patients. CONCLUSIONS The results suggest a relationship between CRVO and certain risk factors (systemic hypertension, diabetes mellitus, kidney disease, glaucoma, older age) and support the possibility of an association between CRVO and urban location. The findings also support the potential value of medical treatment of underlying medical conditions in preventing occurrence of CRVO.
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