Prevention and Treatment of Retinal Vein Occlusion: The Role of Diet-A Review.

Retinal vein occlusion (RVO) is the second most common retinal disorder. In comparison to diabetic retinopathy or age-related macular degeneration, RVO is usually an unexpected event that carries a greater psychological impact. There is strong evidence to suggest that cardiovascular diseases are the most common risk factors in this pathology and it has long been known that a higher consumption of fish, nuts, fruits, and vegetables has a protective effect against these types of conditions. In the last several years, interest in plant-based diets has grown in both the general population and in the scientific community, to the point to which it has become one of the main dietary patterns adopted in Western countries. The aim of this review is to investigate the potential impact of macro- and micronutrients on retinal vein occlusion.

Oral administration of NSP-116, a free radical scavenger, suppresses the symptoms of retinal vein occlusion in the murine model.

Retinal vein occlusion (RVO) is an intractable eye disease that results in reduced visual acuity, associated with retinal ischemia, hemorrhage, and edema. RVO results in excessive ROS production in the retina, causing inflammation and retinal edema. A free radical scavenger, 4-(4-acetylpiperazin-1-yl)-2-(1H-imidazole-1-yl) aniline (NSP-116), has been reported to demonstrate antioxidative effects and prevent ROS production in the retina. Therefore, NSP-116 may represent a useful drug for treating the pathological symptoms of RVO, such as retinal edema and ischemic symptoms. This study aimed to investigate the effects of NSP-116 in a murine model of RVO. We evaluated the thickness of the retinal layer and the size of the non-perfused area following the oral administration of NSP-116. Moreover, we used western blot analysis to examine the expression levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α, after NSP-116 administration, and examined the localization of 8-hydroxy-2'-deoxyguanosine (8-OHdG), by immunostaining. The findings indicate that NSP-116 suppressed retinal edema and expansion the non-perfused area by suppressing the increased expression of VEGF, TNF-α, and 8-OHdG in the murine RVO model. In conclusion, the oral administration of NSP-116 may serve as an effective pharmacological treatment for the pathological symptoms of RVO.

Anti-VEGF Therapy and Retinal Photocoagulation to Prevent Recurrence of Central Retinal Vein Occlusion: Two Case Reports of Young Patients.

Case 1: An 18-year-old man. On initial examination, he was diagnosed with central retinal vein occlusion (CRVO) due to optic papillitis. He had no previous systemic and ocular medical history. His best corrected visual acuity was 20/20 for the right eye, but macular edema accompanied by serous retinal detachment was observed about 2 months after the initial examination. Intravitreal anti-VEGF injection was performed, and the symptoms improved. Then, additional photocoagulation was applied to the retinal nonperfusion area, to maintain its normal state. Case 2: A 36-year-old man. He was diagnosed with neovascular glaucoma associated with CRVO in the right eye by his previous physician. Panretinal photocoagulation and intravitreal anti-VEGF injection were performed under maximum-tolerated medical therapy for the right eye. He had diabetes. On initial examination, his visual acuity was 20/100 and his intraocular pressure was 19mmHg. Macular edema and iris neovascularization recurred half a year later, so intravitreal anti-VEGF injection and additional photocoagulation were applied to nonperfusion area. After that, both macular edema and iris neovascularization have settled down. Conclusions: Intravitreal anti-VEGF injection is effective in young patients with CRVO. Also, photocoagulation to nonperfusion area in addition to the continuous treatment with intravitreal anti-VEGF injection seems effective for preventing recurrence.

Recurrent retinal vein thrombosis: prevention with Aspirin, Pycnogenol®, ticlopidine, or sulodexide.

BACKGROUND: The aim of this study is to evaluate the use of Aspirin, Pycnogenol®, ticlopidine, and sulodexide to reduce the incidence of new RTV (retinal vein thrombosis) after a first episode. Pycnogenol® is an anti-inflammatory, anti-edema, mild antiplatelet-antithrombotic agent. METHODS: The registry study evaluated the number of repeated episodes of RVT in 12 months. Possible managements were: standard management (SM); SM + Aspirin (100 mg/once day; if there were no tolerability problems); SM + Pycnogenol (100 mg/day); SM and ticlopidine (200 mg/day); SM + sulodexide (500 ULS/day). The number of subjects age and sex, distribution, the percent of smokers, the vision were comparable at inclusion. RESULTS: 307 subjects completed the study, 44 in the SM group, 90 in the Pycnogenol® group, 90 in the aspirin group, 45 in the ticlopidine group and 38 in the sulodexide group. At 12 months, recurrent RVT was documented in 22.7% of controls (SM), 3.3% of Pycnogenol® subjects (P<0.05 vs. SM; 19.4% difference). There were RVTs in 15.5% subjects using Aspirin (-7.2% vs. SM). Ticlopidine also reduced (P<0.05) the incidence of RVT in comparison with SM (-9.1%). Sulodexide reduced the occurrence of new RVT (-9.5% vs. SM). Edema was better controlled with the supplement than with all other treatments (P<0.05) (edema present in only 5.5% of the Pycnogenol® subjects). Pycnogenol® had a very good tolerability and safety profile (no patient had to stop treatment). CONCLUSIONS: Pycnogenol® is the only product able to control edema and this may reduce the incidence of recurrent RVT. This retrospective registry indicates that Aspirin, Pycnogenol®, ticlopidine an sulodexide reduce recurrent RVT without side effects. Larger studies should be planned to involve a wider range of conditions, diseases and risk factors associated with RVT and to its recurrence.

Investigational drugs for retinal vein occlusion.

INTRODUCTION: Retinal vein occlusion (RVO) is the second most common retinal vascular disorder. This multifactorial disease frequently leads to visual impairment. Some risk factors for RVO can be managed prophylactically. Given the complex physiopathology of RVO, most of the latest therapeutic strategies focus on secondary clinical features (such as macular oedema and neovascularization). AREAS COVERED: This author reviews ongoing, prospective, open-label Phase I and Phase II clinical trials of novels treatments for RVO (primarily intravitreal steroids and anti-VEGF agents). Specifically, they review the pharmacokinetics, safety profile, study design and adverse events associated with innovative drugs in clinical development. EXPERT OPINION: A number of innovative, early-phase clinical trials are based on combination therapy with an anti-VEGF agent and steroids. There is good evidence that early treatment of RVO has clinical benefits. Larger, randomized studies are now required for a better understanding of patient selection, treatment timing and dosing, and thus the optimized use of novel drugs and medical devices.

[Changes in hemostasis-related parameters of blood and lacrimal fluid in patients with retinal vein occlusion]. / Sostoianie sistemy gemostaza krovi i sleznoi zhidkosti pri okkliuzii retinal'nykh ven.

High prevalence of retinal vein occlusion in young people as well as treatment complexity and inadequate control of hemostatic parameters of blood and lacrimal fluid determine the significance of relevant research in patients with retinal vascular pathology. The data thus obtained may be useful for disease prognosis, severity evaluation and therapy control. This review is aimed to study hemostasis-related parameters of blood and lacrimal fluid in such patients.

Spatio-Temporal Signatures to Predict Retinal Disease Recurrence.

We propose a method to predict treatment response patterns based on spatio-temporal disease signatures extracted from longitudinal spectral domain optical coherence tomography (SD-OCT) images. We extract spatio-temporal disease signatures describing the underlying retinal structure and pathology by transforming total retinal thickness maps into a joint reference coordinate system. We formulate the prediction as a multi-variate sparse generalized linear model regression based on the aligned signatures. The algorithm predicts if and when recurrence of the disease will occur in the future. Experiments demonstrate that the model identifies predictive and interpretable features in the spatio-temporal signature. In initial experiments recurrence vs. non-recurrence is predicted with a ROC AuC of 0.99. Based on observed longitudinal morphology changes and a time-to-event based Cox regression model we predict the time to recurrence with a mean absolute error (MAE) of 1.25 months comparing favorably to elastic net regression (1.34 months), demonstrating the benefit of a spatio-temporal survival model.

Resultados coste-efectividad del implante de dexametasona en edema macular / A cost-effectiveness study of dexamethasone implants in macular edema

OBJETIVO: Analizar el beneficio coste-efectividad del implante intravítreo de dexametasona (Ozurdex®, Allergan, Irvine, CA, EE. UU.) en sus aplicaciones clínicamente relevantes. MATERIAL Y MÉTODOS: Un total de 88 ojos de 86 pacientes con edema macular de > 300 μm medido mediante tomografía de coherencia óptica (Zeiss Cirrus, Dublín, CA, EE. UU.) fueron incluidos en este trabajo retrospectivo de 2 años, con un seguimiento mínimo de 6 meses. Se incluyeron 3 grupos de pacientes: el grupo 1 con edema macular en oclusión venosa retiniana, el grupo 2 con uveítis posterior no infecciosa y el grupo 3 con edema macular diabético, estando este fuera de indicación pero avalado por la literatura médica. Antes del implante y los días 1, 30, 60, 90 y 180 se evaluó la agudeza visual corregida (Snellen), espesor retiniano central, presión intraocular y biomicroscopia. Los análisis de coste-beneficio se tabularon por línea de visión ganada, comparando las principales alternativas terapéuticas, y se valoró el perfil de seguridad del implante intravítreo de dexametasona (Ozurdex®; Allergan, Irvine, CA, EE. UU.). RESULTADOS: Los resultados de este estudio no difirieron de los publicados por otros, en términos de mejoría de la agudeza visual en el 63,3% y del espesor macular central en el 97%. En los casos de recidiva, se produjo a los 120 días de media; la necesidad de retratamiento fue del 40,9%. Entre los efectos secundarios, el incremento de presión intraocular > 23 mm Hg se produjo en el 29,54%, controlándose con tratamiento tópico, excepto un 1,13% de los casos que requirieron tratamiento quirúrgico. El desarrollo de catarata fue del 44,7%, requiriendo cirugía un 10,6%. Los resultados del tratamiento mostraron una menor necesidad en la frecuencia del uso de Ozurdex® frente a otros tratamientos para el control de la enfermedad, convirtiéndose en una opción que permite el ahorro de costes. DISCUSIÓN: Los análisis coste-efectividad son clínicamente relevantes cuando se aplican estrategias terapéuticas en pacientes con edema macular. El implante de dexametasona intravítrea es una opción terapéutica segura y eficiente

OBJECTIVE: To analyze the cost-effectiveness and benefits of a dexamethasone intravitreal implant (Ozurdex®, Allergan, Irvine, CA, USA.) in its clinically relevant applications. MATERIAL AND METHODS: A total of 88 eyes of 86 patients with macular edema of > 300 μm measured by optical coherence tomography (Cirrus Zeiss, Dublin, CA, USA) were included in this two-year retrospective study, with a minimum of 6 months follow-up. The patients were divide into 3 groups: group 1 with macular edema in retinal vein occlusion, group 2 with non-infectious posterior uveitis, and group 3 with diabetic macular edema. The treatment was off-label but supported by the literature. Before implantation, and on days 1, 30, 60, 90 and 180, corrected visual acuity (Snellen), central retinal thickness, intraocular pressure and biomicroscopy were evaluated. The cost-benefit analysis was tabulated by line of visual acuity gained, comparing the main therapeutic alternatives and assessment of the safety profile of the dexamethasone intravitreal implant (Ozurdex®, Allergan, Irvine, CA, USA). RESULTS: The results of this study did not differ from the published studies, in terms of visual acuity improvement in 63.3% of cases, and with central macular thickness improvement in 97% of cases. There were relapses, which occurred after 120 days on average, and the need for retreatment was 40.9%. Increased intraocular pressure >23 mm Hg was among the side effects in 29.54%, and was controlled with topical treatment, except in 1.13% requiring surgical treatment. The development of cataract was 44.7%, and 10.6% required surgery. Treatment results showed less frequent use of Ozurdex® than other treatments for disease control, being a cost saving option. DISCUSSION: Cost-effectiveness analyses are clinically relevant when applying treatment strategies in patients with macular edema. Dexamethasone intravitreal implant appears to be a safe and efficient therapy

[The correlation between carotid stenosis detected by neck vascular ultrasound and branch retinal vein occlusion].

OBJECTIVE: To discuss the clinical significance of the neck vascular ultrasound examination in patients with branch retinal vein occlusion (BRVO). METHODS: Case-control study. Thirty patients of BRVO and 30 healthy subjects with no ophthalmic and systemic symptoms were recruited from January 2010 to January 2012 in the Department of Ophthalmology of the First People's Hospital of Dali Prefecture. The neck vascular ultrasound examination was performed in two groups. The incidence of carotid atheromatous plaque, the rate of carotid stenosis and the carotid artery resistance index (RI) were compared using chi square test. Logistic regression analysis of the rate of carotid stenosis and carotid artery RI were performed. RESULTS: In BRVO group, 23 cases had carotid atheromatous plaque with the incidence of 76.7% Nineteen cases had carotid stenosis with the incidence of 63.3%. The average carotid artery RI was 0.66. In control group, carotid artery atheromatous plaque was found on 6 subjects with incidence of 20.0%. Carotid artery stenosis was detected in 3 subjects with incidence of 10.0%. The average carotid artery RI was 0.61. The incidence of carotid artery atheromatous plaque and carotid stenosis and carotid artery RI in BRVO group were significantly higher than the control group. The difference was statistically significant (P < 0.05). Logistic regression analysis showed that carotid artery stenosis (partial regression coefficien t = 2.263, OR = 9.611, P = 0.004) and carotid artery RI (partial regression coefficien t = 23.713, OR = 669.273, P = 0.006) had influence in BRVO patients as risk factors. CONCLUSION: Early detection of carotid scleratheroma and carotid artery stenosis by the carotid artery ultrasound examination played an important role in prevention or treatment of BRVO.

Vascular endothelial growth factor a in intraocular vascular disease.

UNLABELLED: The vascular beds supplying the retina may sustain injury as a result of underlying disease such as diabetes, and/or the interaction of genetic predisposition, environmental insults, and age. The vascular pathologic features observed in different intraocular vascular diseases can be categorized broadly as proliferation, exemplified by proliferative diabetic retinopathy, leakage such as macular edema secondary to retinal vein occlusion, or a combination of proliferation and leakage, as seen in neovascular age-related macular degeneration (AMD). The World Health Organization has identified diabetic retinopathy and AMD as priority eye diseases for the prevention of vision loss in developed countries. The pathologic transformations of the retinal vasculature seen in intraocular vascular disease are associated with increased expression of vascular endothelial growth factor A (VEGF), a potent endothelial-specific mitogen. Furthermore, in model systems, VEGF alone is sufficient to trigger intraocular neovascularization, and its inhibition is associated with functional and anatomic improvements in the affected eye. Therapeutic interventions with effect on VEGF include intraocular capture and neutralization by engineered antibodies or chimeric receptors, downregulation of its expression with steroids, or alleviation of retinal ischemia, a major stimulus for VEGF expression, with retinal ablation by laser treatment. Data from prospective randomized clinical trials indicate that VEGF inhibition is a potent therapeutic strategy for intraocular vascular disease. These findings are changing clinical practice and are stimuli for further study of the basic mechanisms controlling intraocular angiogenesis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

[Combined retinal artery and vein occlusions associated with interferon beta therapy]. / Kombinierter retinaler arteriovenöser Verschluss unter Interferon-ß-Therapie.

Interferon (IFN) beta is commonly used in the treatment of multiple sclerosis. Thromboembolic complications may be associated with this therapy. We describe a case of branch arterial occlusions combined with central vein occlusion in a female patient who had undergone IFN beta therapy for 10 years. Thromboembolic and cardiovascular risk factors responsible for this event were excluded. The appearance of retinal vein and artery occlusions in our patient indicates an association with the long-term use of IFN beta.

Activated protein C rescues the retina from ischemia-induced cell death.

PURPOSE: Ischemia causes severe and persistent visual loss in many eye diseases, including central retinal vein occlusion (CRVO) and diabetic retinopathy. Activated protein C (APC) has been demonstrated to reduce the cell death associated with ischemia in the brain and kidney. This study was performed to examine the ability of APC to rescue hypoxia-induced retinal cell death in vitro and in vivo. METHODS: Retinal pigment epithelium (RPE) and photoreceptor cells were placed in either a normoxic or a hypoxic chamber. Immediately before they were subjected to ischemia, the cultures were treated with APC (3-240 µg/mL). Incubation was followed by an MTT assay to determine the number of viable cells. The activity of caspase-3, -8, and -9 in RPE cells was also analyzed. Various concentrations of APC were intravitreally injected in a rat CRVO model, followed by TUNEL staining to detect the in vivo effects of APC. RESULTS: Lower concentrations of APC (0.3-30 µg/mL) showed a cell-protective effect against hypoxia in vitro, whereas higher concentrations (≥120 µg/mL) demonstrated cytotoxicity in both RPE and photoreceptor cells. Caspase-3, -8, and -9 were activated when the cells were exposed to hypoxia, but this activation was significantly inhibited by APC. Experimental CRVO-induced retinal cell apoptosis was reduced dramatically by intravitreal injection of APC. CONCLUSIONS: APC can reduce ischemia-induced cytotoxicity both in vitro and in vivo via blocking the activation of caspase-3, -8, and -9. APC may be a promising candidate for protecting the retina from ischemia.

Retinal vein occlusion: evaluation of "classic" and "emerging" risk factors and treatment.

Retinal vein occlusion (RVO) is the second most common retinal vein disease and an important cause of blindness and visual morbidity. Systemic risk factors are commonly associated with RVO, while unclear it is the role of the thrombophilic and coagulation disorders. To evaluate "classic" and "emerging" risk factors, and to establish a good treatment for RVO. Fifty patients, 31 males and 19 females, with RVO were selected for our study. RVO patients were divided into two groups: those with central retinal vein occlusion (CRVO) and those with branch retinal vein occlusion (BRVO). All patients were subjected to an anamnestic investigation and were tested for thrombophilia, coagulation disorders and hyperlipidemia. Treatment and prophylaxis were evaluated. We have named "classic" the systemic risk factors associated with RVO and "emerging" those risk factors, haemostasis related, not clearly associated with RVO. RVO occurs more commonly in patients aged over 50. "Emerging" risk factors were more frequent in CRVO, "classic" in BRVO. Hyperhomocysteinemia is the most common "emerging" risk factor related to RVO. 71.4% of tested patients had hypercholesterolemia. Treatment with LMWH would appear to be safe and effective, but the small number of patients considered not allow us a definitive evaluation of its efficacy. Although our study has shown the correlation between RVO and the "emerging" risk factors, more studies are necessary to better know the real role of thrombophilic and coagulation disorders in this disease and to determine a specific protocol for the treatment and prophylaxis of RVO.

Atypical peripapillary location of choroidal neovascularization--case reports.

UNLABELLED: Choroidal neovascularization (CNV) is one of the main reasons for sight loss in adults. CNV located at the border of the optic disc or adherent atrophy is described as peripapillary choroidal neovascularisation (PPCNV). The aim of the work is to present a course of changes and the effects of treatment with intravitreal ranibizumab injections for peripapillary subretinal neovascularization, its consequences and accompanying other CNV foci in two patients. The diagnosis and monitoring of the therapeutic effects were based on the results of fluorescein angiography and OCT. In a 53-year-old female patient three injections of ranibizumab at a dose of 0.05 mg were administered according to a saturation regimen. Visual improvement of 5 lines on an ETDRS board (25 letters) was obtained, as well as withdrawal of the subretinal fluid from the area of the macula in OCT and limitation of the peripapillary exudate visible in 12 months follow-up angiography. In a 70-year-old female patient bilateral development of symmetric peripapillary CNV foci was observed accompanied by a occult CNV focus in the left eye macula. Spontaneous CNV limitation without macular lesions was visible in the right eye. Intravitreal ranibizumab injections were given into the left eye. A 12 months follow-up revealed vision stabilisation in both eyes at the baseline level. CONCLUSIONS: Intravitreal injections can be used in the treatment of atypical extramacular CNV, responsible for secondary damage to the fovea. Ranibizumab, a non-selective VEGF-A inhibitor, allows the elimination of changes in the central retina, closure or significant limitation of the exudates and vision improvement. Spontaneous limitation of lesions may also be frequently expected in the eyes with peripapillary CNV foci.

Effects of exercise on ocular physiology and disease.

Regular exercise is a healthy lifestyle choice with numerous benefits to general health. Ophthalmologists may face questions of the benefits or risks of exercise to eyes. Here the effects of acute exertion and regular physical activity on ocular physiology and disease are reviewed. Intraocular pressure is transiently reduced by dynamic exercise. For the great majority of patients exercise is beneficial to the eyes by reducing risk of central retinal vein occlusion and neovascular age-related macular degeneration, and by improving control of systemic hypertension and diabetes. Ophthalmologists should be advocates of regular exercise with appropriate eye protection.

[Antiphospholipid syndrome and retinal vein occlusion. Meta-analysis of Published Studies]. / Antiphospholipidsyndrom und retinale venöse Verschlüsse. Metaanalyse publizierter Studien.

The role of antiphospholipid syndrome (APS) in the pathogenesis of retinal vein occlusion has been discussed for several years. Conflicting results of the published studies are caused by small numbers of investigated patients and lack of control groups. We performed a meta-analysis of all case-control studies published up to July 2007 that investigated the prevalence of APS according to current diagnostic criteria for this syndrome.The results of meta-analysis show a significantly higher prevalence of APS in patients with retinal vein occlusion compared with controls. Patients with APS are treated with anticoagulants to reduce the risk of recurrence of thrombosis. Therefore, screening for APS seems to be indicated in all patients with retinal vein occlusion, and, in the case of a positive result, initiation of anticoagulation. For patients with retinal vein occlusion with APS, no data are currently available regarding the recurrence of thrombosis. To give a clear recommendation, a prospective randomized study is required to investigate the benefit of anticoagulation.