Fig 3 - uploaded by Christine Kiire
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Left superotemporal branch retinal vein occlusion. Note the retinal haemorrhages in the superotemporal quadrant and in the macular area (white arrows). The blurred appearance at the macula (circle) is suggestive of macular oedema
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#### Summary points
Retinal vein occlusion—obstruction of the retinal venous system by thrombus formation, external compression, or disease of the vein wall1—is the second most common retinal vascular disease after diabetic retinopathy.2 Pooled data from population studies in the United States, Europe, Asia, and Australia suggest that about 16 mil...
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Design:
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Participants:
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Neovascularization is a common pathological process in various retinal vascular disorders including diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinal vein occlusion (RVO). The development of neovascular vessels may lead to complications such as vitreous hemorrhage, fibrovascular tissue formation, and traction retinal det...
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Phase IIIb, open-label, r...
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Citations
... The most common retinal manifestation of lifestyle diseases such as arterial sclerosis and hypertension is diabetic retinopathy, followed by branch retinal vein occlusion (BRVO) [1,2]. Patients with BRVO can become visually impaired, primarily due to macular edema [1]. ...
Background and Objectives: To investigate peripheral blood flow in retinal vessels and vessel diameters after intravitreal ranibizumab injection (IRI) and the relationship between these parameters and cytokines in branch retinal vein occlusion (BRVO) with macular edema. Materials and Methods: We assessed relative flow volume (RFV) and the width of the main and branch retinal arteries and veins in the occluded and non-occluded regions before and after IRI in 37 patients with BRVO and macular edema. Measurements were made using laser speckle flowgraphy (LSFG). When performing IRI, we obtained samples of aqueous humor and analyzed them using the suspension array method to evaluate vascular endothelial growth factor (VEGF), placental growth factor (PlGF), platelet-derived growth factor (PDGF)-AA, soluble intercellular adhesion molecule (sICAM)-1, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL)-6, IL-8, and interferon-inducible 10-kDa protein (IP-10). Results: In both retinal regions, before and after IRI, the RFV in the main artery and vein showed a significant correlation with the summed RFV in the respective branch vessels 1 and 2. In the occluded region, the RFV in the main vein was significantly negatively correlated with MCP-1, PDGF-AA, IL-6, and IL-8; the RFV in branch vein 1 was significantly negatively correlated with PlGF, MCP-1, IL-6, and IL-8; PDGF-AA was significantly negatively correlated with the width of the main and branch veins; and the RFVs of the main artery and vein decreased significantly from before to 1 month after IRI. Conclusions: Contrary to expectations, the study found that anti-VEGF therapy does not affect RFV in arteries and veins in patients with BRVO and macular edema. Furthermore, retinal blood flow is poor in patients with high MCP-1, IL-6, and IL-8. Finally, high PDGF-AA may result in smaller venous diameters and reduced retinal blood flow.
... Macular edema caused by capillary fluid leakage in the central macular area is the most common cause of vision loss in patients with RVO 40 . ...
... In cases of established neovascular glaucoma and blindness, the goal should be pain control with the use of topical steroids and atropine. However, if there is a prognosis of preserved vision, intraocular pressure control with hypotensive eye drops or surgery should be sought 40 . ...
... Several case series (without controls) indicate that around 50% of patients with non-ischemic central retinal vein occlusion and branch retinal vein occlusion have a visual acuity gain of two or more lines with intravitreal bevacizumab. Vision stabilized by 12 months in 90% of eyes (1). Some study, in adult patients, showed improvement of central vein occlusion after injection of intravitreal ranibizumab (12). ...
Introduction:
Retinal vein occlusions (RVOs) are rare in the younger population. Hematological pro-thrombotic factors are thought to be important in a minority, amplifying an atherosclerotic anatomical predisposition.
Case report:
Anotherwise healthy 13-year-old girl presented two episodes of sudden decreased vision in few months.Ophthalmological exams pointed out post-thrombotic intra-retinal hemorrhage. All investigations were normal, thrombophilia screen showed factor XII deficiency and genetic mutations of methylenetetrahydrofolate reductase (MTHFR), angiotesin convertin enzyme (ACE) and angiotensinogen (AGT). Two intravitreal injection of bevacizumab was administered with improving visual acuity; subsequently the patient did not report further episodes.
Discussion:
In addition to traditional factors with procoagulant activity, factor XII deficiency plays an important role in thrombosis's mechanism. Its deficiency causes a marked prolongation of the activated partial thromboplastin time in the laboratory examination. Moreover also MTHFR, ACE and AGT could have been involved in this case, so it is important to evaluate these parameters in the differential diagnosis of RVOs.
... Ischemic RVO (iRVO) is the most severe form, associated with higher risk of complications and having a poorer prognosis than non-iRVO. 1,2,4,15,17,18 Current treatments of RVO, including laser photocoagulation, intravitreal anti-VEGF therapies, intravitreal steroids, and pars plana vitrectomy, target the complications of RVO, namely macular edema and neovascularization and its consequences, 1,5,7,16,17,[19][20][21][22][23][24] and may not fully reverse the functional and structural damage result of the disease. 10, Furthermore, each of these treatments carries a risk to patients, such as destruction of the retina following laser photocoagulation, endophthalmitis following intravitreal injections, and cataract and glaucoma as a result of steroid administration. ...
Purpose:
To provide a comprehensive and current review on the available experimental animal models of retinal vein occlusion (RVO) and to identify their strengths and limitations with the purpose of helping researchers to plan preclinical studies on RVO.
Methods:
A systematic review of the literature on experimental animal models of RVO was undertaken. Medline, SCOPUS, and Web of Science databases were searched. Studies published between January 1, 1965, and March 31, 2017, and that met the inclusion criteria were reviewed. The data extracted included animal species used, methods of inducing RVO, and the clinical and histopathologic features of the models, especially in relation to strengths, limitations, and faithfulness to clinical sequelae.
Results:
A total of 128 articles fulfilling the inclusion criteria were included. Several species were used to model human branch and central RVO (BRVO; CRVO) with nonhuman primates being the most common, followed by rodents and pigs. BRVO and CRVO were most commonly induced by laser photocoagulation and all models showed early features of clinical disease, including retinal hemorrhages and retinal edema. These features made many of the models adequate for studying the acute phase of BRVO and CRVO, although macular edema, retinal ischemia, and neovascular complications were observed in only a few experimental animal models (laser-induced model in rodents, pigs, and nonhuman primates, diathermy-induced model in pigs, and following intravitreal injection of PD0325901 in rabbits for BRVO; and in the laser-induced model in rodents, rabbits, and nonhuman primates, diathermy-induced model in nonhuman primates, following permanent ligation of the central retinal vein in nonhuman primates, and with intravitreal injection of thrombin in rabbits for CRVO).
Conclusions:
Experimental animal models of RVO are available to study the pathogenesis of this disease and to evaluate diagnostic/prognostic biomarkers and to develop new therapeutics. Data available suggest laser-induced RVO in pigs and rodents to be overall the best models of BRVO and the laser-induced RVO rodents the best model for CRVO.
... 17 In fact, RVO, obstruction of the retinal venous system by thrombus formation, external compression, or disease of the vein wall, is the second most common retinal vascular disease after diabetic retinopathy. 18 Retinal vein occlusion occurs with equal sex distribution, especially in middle-aged and older individuals with a history of systemic arterial hypertension, diabetes, or generalized atherosclerotic disease. Each of these risk factors is a complex trait, determined also by genetic profiles. ...
Apolipoprotein E (APOE) is a member of the apolipoprotein gene family. APOE is polymorphic with 3 main allelic types: ∊2, ∊3, and ∊4. Certain of these alleles have been associated with higher vascular risk. However, the association of APOE genotypes with retinal biomarkers and risk of retinal stroke is less clear. This study evaluated the role of APOE polymorphisms in retinal vein occlusion (RVO). In the present study, 2-point mutations coding amino acid residues 112 and 158 were amplified using the polymerase chain reaction (PCR) from DNA extracted from Tunisian participants. APOE genotypes were determined by multiplex PCR followed by molecular hybridization. Eighty-eight patients (26 women and 62 men) and 100 age- and gender-matched healthy participants were enrolled. The statistical study revealed a higher frequency of the ∊4 allele in patients as compared to controls (27.3% vs 9%) with a significant association of the ∊4 allele with the disease (P < 10−3, P a < 10−3, odds ratio [OR] = 3.8, 95% confidence interval [CI] = 2.1-6.8). The frequency of the ∊3 allele was significantly lower in the patients with RVO compared to the controls (60.2% vs 82.5%, respectively; P < 10−3, P a < 10−3, OR = 0.32, 95% CI = 0.19-0.53). The ∊3 allele seems to be protective against the disease. There was no association between the APO ∊2 allele and RVO. The association of APOE allele and genotype with RVO requires further investigation in different populations.
... Dada la compleja patogenia de la TVR se aconseja que en estos pacientes se realice una valoración sistémica, que sirva para decidir el tratamiento más apropiado, con el objetivo de prevenir daños sistémicos asociados y recurrencias 4,16,19,20 . No existe consenso sobre los parámetros que se deben estudiar 4,10 . ...
... Vision loss from macular edema or scarring associated with retinal neovascularization has become the leading cause of blindness in people aged 50 years or older. For example, incidences of diabetic macular edema 2,3 and macular edema from retinal vein occlusions 4,5 have been on the rise and the expenditure associated with their medical care is challenging for the medical community and the patients it serves. 6 Even in a booming era of biological therapeutics, steroids still are a major player in the medical care of these refractory eye diseases due to their wellestablished efficacy at a fraction of the expense of anti-VEGF biological therapeutics. ...
Purpose
The current study aims to evaluate a porous silicon-based drug delivery system meant for sustained delivery of dexamethasone (Dex) to the vitreous and retina.
Methods
Dexamethasone was grafted covalently into the pore walls of fully oxidized porous silicon particles (pSiO2-COO-Dex), which then was evaluated for the pharmacological effect of the payload on cultured ARPE19 cells before intravitreal injection. The Dex release profile was investigated in a custom designed dynamic dissolution chamber to mimic the turnover of vitreous fluid in rabbit eyes. Ocular safety, in vivo release, and pharmacodynamics were evaluated in rabbit eyes, and the human VEGF-induced rabbit retinal vascular permeability model.
Results
Loading efficiency of Dex was 69 ± 9 μg per 1 mg of the pSiO2-COO-Dex particles. Dynamic in vitro release demonstrated a sustained mode when compared to free Dex, with the drug half-life extended by 5 times. The released Dex was unaltered and biologically active. In vivo drug release in rabbit eyes revealed a mode similar to the release seen in vitro, with a vitreous half-life of 11 days. At 2 and 4 weeks after a single intravitreal injection of pSiO2-COO-Dex particles (mean 2.71 ± 0.47 mg), intravitreal 500 ng of VEGF did not induce significant retinal vessel dilation or fluorescein leakage, while these events were observed in the eyes injected with empty pSiO2 particles or with free Dex. The retinal vessel score from fluorescein angiography for the control eyes was double the score for the eyes injected with pSiO2-COO-Dex. No adverse reaction was observed for the eyes injected with drug-loaded pSi particles during the course of the study.
Conclusions
The porous silicon-based Dex delivery system (pSiO2-COO-Dex) can be administered safely into vitreous without toxicity. Dex release from the porous silicon particles was sustained for 2 months and was effective against VEGF-induced retinal vessel reaction.
... По мнению большинства исследователей, в остром периоде при окклюзии основного ствола ЦВС МО возникает в 100% случаев. По данным некоторых статистических исследований [3,4], спонтанная ремиссия МО происходит у трети пациентов с неишемическим подтипом окклюзии ЦВС. Точных данных о частоте и сроках спонтанной ремиссии МО нет, но в исследовании «Central Vein Occlusion Study» у 65% пациентов с изначальной остротой зрения (в остром периоде) 0,5 и более в течение 3 лет наблюдалась тенденция к повышению остроты зрения без какого-либо лечения. ...
Macular edema (ME) is the most common complication of both ischemic and nonischemic retinal vein occlusion (RVO). If the main trunk of the central retinal vein is involved, ME occurs in 100% of cases. According to the Central Vein Occlusion Study, in 65% of RVO and ME patients with baseline visual acuity (VA) of at least 0.5 (Golovin-Sivtsev chart) or higher, ME may resolve itself without treatment with subsequent VA improvement. Therefore, we recommend a 3-month treatment-free follow-up of nonischemic central RVO (CRVO) and ME patients with VA of 0.5 or higher. If no improvement is noted within this period, treatment is initiated. Immediate treatment is required in patients with cystic ME revealed by optical coherence tomography (OCT) and VA below 0.5. Ischemic maculopathy is extremely unpromising. Modified grid laser photocoagulation should not be used as monotherapy for macular edema. Repeated corticosteroid (Ozurdex) and/or anti-VEGF (ranibizumab, aflibercept) intravitreal injections are considered the first choice treatment for ME in CRVO patients. Efficiency assessments should include monthly OCT. For persistent ME, intravitreal therapy can be supplemented by laser retinal photocoagulation (panretinal or modified grid). Anti-VEGF treatment schemes should be adjusted in BRVO patients as most of their edemas are self-limiting. Of laser photocoagulation techniques, only modified grid is used.
... Virchow' triad [58] . From modern perspectives , retinal vein occlusion might be resulted from the compression of the retinal vein by a thickened adjacent retinal artery [59]. Secondly, a substantial number of new original articles were included in our meta-analysis, endowing a greater statistical power. ...
... Patients presenting with a best-corrected visual acuity (BCVA) of < 6/24 to 6/60 improved upon their visual acuity or maintained it at the initial level in both the groups. Likewise, other studies showed that the eyes with an initial visual acuity of at least 6/12 were more likely to retain good vision (Kiire and Chong, 2012). Neo-vascular glaucoma (NVG) was diagnosed in 15 (20.27 %) patients and all of them had the ischemic type of CRVO. ...
Background:
Central retinal vein occlusion (CRVO) is one of the common retinal disorders causing severe visual impairment.
Objective:
To study the clinical profile, risk factors and visual outcome in central retinal vein occlusion.
Materials and methods:
Seventy-four eyes of 74 patients with central retinal vein occlusion were retrospectively enrolled during the period of one year. All the patients in the study were classified with regard to their ischemic status into two groups, ischemic CRVO and non-ischemic CRVO. The demographic pattern of the patients was recorded. The other parameters studied were visual acuity, history of glaucoma, hypertension, diabetes mellitus and hyperlipidemia. The patients were followed up at 1 month, 3 months and 6 months after treatment.
Results:
The majority of the patients (n = 49, 66.2 %) had the ischemic type of CRVO, whereas, 25 (33.8 %) of them had the non-ischemic type. The CRVO was more commonly observed in males in both the groups. Hypertension was the most common risk factor associated with CRVO. The visual improvement was significantly better in non-ischemic CRVO (RR = 0.04, 95% CI = 0.01 - 0.31, p = 0.000).
Conclusion:
The CRVO was more common in males than in females. It was associated with systemic hypertension. The ischemic type of the CRVO was more prevalent than the non-ischemic one in this study. Visual outcome was better in the non-ischemic CRVO.
