RESUMEN
Inherited retinal diseases (IRDs) are the most common cause of blindness in working-age adults. Macular neovascularization (MNV) may be a presenting feature or occurs as a late-stage complication in several IRDs. We performed an extensive literature review on MNV associated with IRDs. MNV is a well-known complication of Sorsby fundus dystrophy and pseudoxanthoma elasticum. Those with late-onset Stargardt disease may masquerade as exudative age-related macular degeneration (AMD) when MNV is the presenting feature. Peripherinopathies may develop MNV that responds well to a short course of anti-vascular endothelial growth factor (anti-VEGF) therapy, while bestrophinopathies tend to develop MNV in the early stages of the disease without vision loss. Enhanced S-cone syndrome manifests type 3 MNV that typically regresses into a subfoveal fibrotic nodule. MNV is only a rare complication in choroideraemia and rod-cone dystrophies. Most IRD-related MNVs exhibit a favorable visual prognosis requiring less intensive regimens of anti-vascular endothelial growth factor therapy compared to age-related macular degeneration. We discuss the role of key imaging modalities in the diagnosis of MNV across a wide spectrum of IRDs and highlight the gaps in our knowledge with respect to the natural history and prognosis to pave the way for future directions of research.
Asunto(s)
Neovascularización Coroidal , Degeneración Macular , Degeneración Retiniana , Neovascularización Retiniana , Adulto , Humanos , Factores de Crecimiento Endotelial , Retina , Degeneración Macular/complicaciones , Degeneración Macular/diagnóstico , Degeneración Retiniana/complicaciones , Neovascularización Patológica , Angiografía con Fluoresceína , Tomografía de Coherencia Óptica , Estudios Retrospectivos , Neovascularización Retiniana/complicacionesRESUMEN
Purpose: Cystoid macular degeneration (CMD) is a feature of chronic central serous chorioretinopathy (CSCR). Present study intended to analyze the clinical presentation, risk factors, choroidal features, and outcome of CMD in CSCR. Methods: This was a retrospective, record-based descriptive study, which included chronic CSCR eyes with CMD. Demographic profile and clinical history were obtained from medical records. Spectralis spectral domain optical coherence tomography (SDOCT; Heidelberg Engineering,Germany) was used for acquiring SDOCT images and for performing fluorescein angiography , indocyanine green angiography , and optical coherence tomography (OCT) angiography. Results: The study included 101 eyes of 69 consecutive patients of CSCR having CMD. The mean age of patients was 56 ± 9.4 years (range 40-79 years), and majority (63, 91.3%) of the patients were male. Prior history of corticosteroid use was present in seven (10.1%) patients. Mean time interval between the first diagnosis of CSCR and appearance of CMD was 55.3 ± 33.9 months. CMD was located away from the fovea in majority of eyes (68, 67.3%). Mean subfoveal choroidal thickness was 396.71 ± 90.5 µm. Subretinal pigment epithelium choroidal neovascularization was noted in four (3.96%) eyes. Conclusion: CMD appears as a late complication of CSCR and is usually present away from the fovea. Such eyes had thickened choroid and fewer cases had associated choroidal neovascularization. Further comparative studies would be needed to validate these findings.
Asunto(s)
Coriorretinopatía Serosa Central , Degeneración Macular , Neovascularización Retiniana , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Anciano , Coriorretinopatía Serosa Central/complicaciones , Coriorretinopatía Serosa Central/diagnóstico , Estudios Retrospectivos , Degeneración Macular/complicaciones , Coroides , Tomografía de Coherencia Óptica/métodos , Neovascularización Retiniana/complicacionesRESUMEN
PURPOSE: Characterize clinical and socioeconomic factors that impact follow-up to complete retinal vascularization and subsequent pediatric ophthalmology follow-up in neonates with retinopathy of prematurity. METHODS: Medical records of 402 neonates diagnosed with retinopathy of prematurity from neonatal intensive care units at the University of California, Los Angeles Mattel Children's Hospital and the University of California, Los Angeles Santa Monica Hospital, both academic medical centers, and the Harbor-University of California, Los Angeles Medical Center, a safety-net county hospital, were reviewed. Primary study outcomes were the rate of follow-up to complete retinal vascularization and adequate pediatric ophthalmology follow-up. Secondary outcome was the rate of nonretinal ocular comorbidity. RESULTS: In whole-cohort analysis, 93.6% of neonates were followed to complete retinal vascularization, and 53.5% had adequate pediatric ophthalmology follow-up. Public insurance was associated with lower rates of pediatric ophthalmology follow-up (Odds ratio 0.66, 95% confidence interval 0.45-0.98, P = 0.04). Participants screened at the academic medical center had lower rates of pediatric ophthalmology follow-up compared with the safety-net county hospital (50.7% vs. 63.5%, P = 0.034). In subgroup analysis, academic medical center participants with public insurance were less likely to have pediatric ophthalmology follow-up than safety-net county hospital participants with public insurance (36.5% vs. 63.8%, P < 0.001) or those with private insurance at the academic medical center (36.5% vs. 59.2%, P< 0.001). CONCLUSION: This study identified high follow-up rates to complete retinal vascularization, lower pediatric ophthalmology follow-up rates, and nonretinal ocular comorbidity at all hospitals. Insurance status relative to hospital type was identified as a risk factor for loss to follow-up. This demonstrates a need to further study health care disparities in retinopathy of prematurity infants.
Asunto(s)
Neovascularización Retiniana , Retinopatía de la Prematuridad , Recién Nacido , Lactante , Niño , Humanos , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/epidemiología , Estudios de Seguimiento , Recien Nacido Prematuro , Estudios de Cohortes , Factores de Riesgo , Neovascularización Retiniana/complicaciones , Edad GestacionalRESUMEN
Background: Eales disease is a clinical syndrome affecting the mid-peripheral retina with an idiopathic occlusive vasculitis and possible subsequent retinal neovascularization. The disease can develop into visually threatening complications. Case Presentation: We report the case of a 40-year-old Caucasian male with a history of cocaine abuse who presented with blurred vision in the left eye (LE). Fundus examination showed vitreous hemorrhages, peripheral sheathing of venous blood vessels, areas of retinal neovascularization in the LE, and peripheral occlusive phlebitis in the right eye. The full serologic panel was negative except for the heterozygous mutation of factor V Leiden. Clinical and biochemical parameters suggested a diagnosis of Eales disease. Therapy with dexamethasone, 1 mg per kg per day, tapered down slowly over 4 months, and peripheral laser photocoagulation allowed a regression of clinical signs and symptoms. Conclusion: This case shows an uncommon presentation of Eales disease associated with cocaine abuse. Both cocaine abuse and a thrombophilic pattern, as cofactors, might have sensitized the retinal microcirculation on the pathogenetic route to this retinal pathology. Furthermore, in view of this hypothesis, a thorough ocular and general medical history investigating drug abuse and coagulation disorders is recommended for ophthalmologists in such cases.
Asunto(s)
Trastornos Relacionados con Cocaína , Neovascularización Retiniana , Vasculitis Retiniana , Humanos , Masculino , Adulto , Neovascularización Retiniana/complicaciones , Neovascularización Retiniana/patología , Trastornos Relacionados con Cocaína/complicaciones , Neovascularización Patológica/complicaciones , Vasculitis Retiniana/etiología , Vasculitis Retiniana/complicacionesRESUMEN
Diabetes is a disease that leads to proliferative diabetic retinopathy (PDR), which is associated with an increase of new vessels formation due to an overexpression of angiogenic factors, such as angiopoietin 2 (ANGPT2). The aim of this work was to design a siRNA targeting ANGPT2 to decrease the retinal neovascularization associated with PDR. Adult male Wistar rats weighing 325-375 g were used. Diabetes was induced by a single dose of streptozotocin (STZ, 60 mg/kg i.p.). The siRNAs were designed, synthesised, and administered intravitreally at the beginning of diabetes induction (t0), and after 4 weeks of diabetes evolution (t4), subsequently evaluated the retinal neovascularization (junctions and lacunarity) and ANGPT2 expression in the retina by RT-PCR, after 4 weeks of the siRNAs administration. The results showed that the administration of STZ produced significant increases in blood glucose levels, retinal neovascularization (augmented junctions and lower lacunarity), and ANGPT2 expression, while the administration of the ANGPT2-siRNAs at different groups (t0 and t4) reduces the junctions and increases the lacunarity in diabetic rats. Therefore, we conclude that the administration of siRNAs targeting ANGPT2 could be an option to decrease the retinal neovascularization associated with PDR and halt the progression of blindness caused by diabetes.
Asunto(s)
Diabetes Mellitus Experimental , Retinopatía Diabética , Neovascularización Retiniana , Angiopoyetina 2/genética , Animales , Diabetes Mellitus Experimental/metabolismo , Retinopatía Diabética/genética , Masculino , Neovascularización Patológica/genética , ARN Interferente Pequeño/farmacología , Ratas , Ratas Wistar , Retina/metabolismo , Neovascularización Retiniana/complicaciones , Neovascularización Retiniana/genética , Neovascularización Retiniana/metabolismo , EstreptozocinaRESUMEN
PURPOSE: To investigate demographic and clinical factors influencing the longitudinal changes of retinal pigment epithelium (RPE) dehiscence area after RPE tears, including the presence of RPE tear-associated repair proliferation (TARP), and identify factors associated with TARP development over follow-up. METHODS: Retrospective, single-center, observational cohort study of patients with a history of macular neovascularization and RPE tear. The area of RPE dehiscence was measured on repeated short-wavelength fundus autofluorescence imaging. Associations between covariates and RPE dehiscence areas were tested with multivariable linear mixed models. Associations between TARP development and clinical variables were investigated with Cox regression models. Factors associated with visual acuity changing rates were explored with linear mixed models. RESULTS: Thirty-seven eyes of 36 patients were included in this study and followed for a median time of 18 months. Tear-associated repair proliferation was identified in 27 eyes (73%). The median time for TARP detection was 112 days; none of the investigated factors was significantly associated with TARP occurrence. The presence of TARP (estimate: -0.042 mm2/month; P = 0.001) and female gender (estimate: -0.035 mm2/month; P = 0.006) were associated with slower rates of RPE dehiscence enlargement over time. Faster rates of visual improvement were observed in eyes with TARP compared with those without TARP (estimate = -0.010 logarithm of the minimum angle of resolution/month if TARP was present; P = 0.008). CONCLUSION: Retinal pigment epithelium tear repair with TARP and female gender were associated with slower RPE degeneration after RPE tears. The presence of TARP was associated better visual prognosis. Additional research on factors promoting TARP development may have therapeutic and prognostic implications.
Asunto(s)
Proliferación Celular/fisiología , Perforaciones de la Retina/diagnóstico , Epitelio Pigmentado de la Retina/patología , Cicatrización de Heridas/fisiología , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Humanos , Masculino , Imagen Multimodal , Fotoquimioterapia , Pronóstico , Neovascularización Retiniana/complicaciones , Perforaciones de la Retina/tratamiento farmacológico , Perforaciones de la Retina/etiología , Perforaciones de la Retina/fisiopatología , Estudios Retrospectivos , Factores de Tiempo , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza Visual/fisiologíaRESUMEN
Interferon-γ (IFNG) is one of the key cytokines that regulates both innate and adaptive immune responses in the body. However, the role of IFNG in the regulation of vascularization, especially in the context of Vascular endothelial growth factor A (VEGFa)-induced angiogenesis is not clarified. Here, we report that IFNG shows potent anti-angiogenic potential against VEGFa-induced angiogenesis. IFNG significantly inhibited proliferation, migration, and tube formation of Human umbilical vein endothelial cells (HUVECs) both under basal and VEGFa-treated conditions. Intriguingly, Knockdown (KD) of STAT1 abolished the inhibitory effect of IFNG on VEGFa-induced angiogenic processes in HUVECs. Furthermore, IFNG exhibited potent anti-angiogenic efficacy in the mouse model of oxygen-induced retinopathy (OIR), an in vivo model for hypoxia-induced retinal neovascularization, without induction of functional side effects. Taken together, these results show that IFNG plays a crucial role in the regulation of VEGFa-dependent angiogenesis, suggesting its potential therapeutic applicability in neovascular diseases.
Asunto(s)
Interferón gamma/uso terapéutico , Isquemia/complicaciones , Neovascularización Retiniana/complicaciones , Neovascularización Retiniana/tratamiento farmacológico , Animales , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Hipoxia/complicaciones , Interferón gamma/administración & dosificación , Interferón gamma/farmacología , Inyecciones Intravítreas , Ratones , Neovascularización Fisiológica/efectos de los fármacos , Retina/efectos de los fármacos , Retina/patología , Retina/fisiopatología , Neovascularización Retiniana/fisiopatología , Factor de Transcripción STAT1/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
SIGNIFICANCE: Although von Willebrand disease is the most common inherited bleeding disorder, there are only a few published reports of ocular complications. To our knowledge, this is the first case of peripheral retinal ischemia and retinal neovascularization in a patient with von Willebrand disease. PURPOSE: This study aimed to demonstrate the value of multispecialty care when exploring a diagnosis for bilateral retinopathy. CASE REPORT: A 55-year-old African American woman presented with peripheral retinal hemorrhages on routine examination. She was asymptomatic and did not have any personal or family history of bleeding disorders. Blood work was ordered, and she was referred to a retinal specialist who found peripheral telangiectasia, retinal ischemia, and leakage on fluorescein angiography, consistent with retinal neovascularization. Laser photocoagulation was performed while numerous specialists were consulted to determine the cause for her retinopathy. Laboratory testing confirmed low-grade type 1 von Willebrand disease. She was monitored without systemic treatment. She remained stable and asymptomatic, but her retinal neovascularization did not regress fully, so laser treatment was repeated. CONCLUSIONS: This case described a new finding of peripheral retinal ischemia and retinal neovascularization in von Willebrand disease. It was discovered in an asymptomatic patient who did not have a history of bleeding but presented with bilateral retinal hemorrhages. Diagnosis was challenging because of the high degree of variation in this bleeding disorder, requiring extensive testing and careful consideration of the individual's clinical profile. Most people with von Willebrand disease do not know they have the disease because symptoms are mild or absent, so most cases are unreported. The von Willebrand factor is poorly recognized in ocular disease, but given its role in angiogenesis, it may be a valuable target to consider in future research.
Asunto(s)
Isquemia/etiología , Neovascularización Retiniana/etiología , Vasos Retinianos/patología , Enfermedades de von Willebrand/complicaciones , Femenino , Angiografía con Fluoresceína , Humanos , Isquemia/complicaciones , Isquemia/diagnóstico , Isquemia/fisiopatología , Persona de Mediana Edad , Neovascularización Retiniana/complicaciones , Neovascularización Retiniana/diagnóstico , Neovascularización Retiniana/fisiopatología , Agudeza Visual/fisiología , Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/tratamiento farmacológico , Factor de von Willebrand/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the leading causes of preventable vision loss in the world and its prevalence continues to increase worldwide. One of the ultimate and visually impairing complications of DR is proliferative diabetic retinopathy (PDR) and subsequent tractional retinal detachment. Treatment modalities, surgical techniques, and a better understanding of the pathophysiology of DR and PDR continue to change the way we approach the disease. The goal of this review is to provide an update on recent treatment modalities and outcomes of proliferative diabetic retinopathy and its complications including tractional retinal detachment. RECENT FINDINGS: Panretinal photocoagulation (PRP), anti-vascular endothelial growth factor (anti-VEGF), and pars plana vitrectomy are the mainstay of PDR treatment. However, PRP and anti-VEGF are associated with significant treatment burden and multiple subsequent treatments. Early vitrectomy is associated with vision preservation, less treatment burden, and less subsequent treatments than therapy with PRP and anti-VEGF. SUMMARY: Concerning costs, high rates of noncompliance in the diabetic population and significant rates of subsequent treatments with initial PRP and anti-VEGF, early vitrectomy for diabetic retinopathy in patients at risk of PDR is a cost-effective long-term stabilizing treatment for diabetics with advanced disease.
Asunto(s)
Retinopatía Diabética/cirugía , Desprendimiento de Retina/cirugía , Neovascularización Retiniana/cirugía , Vitrectomía/métodos , Inhibidores de la Angiogénesis/uso terapéutico , Retinopatía Diabética/complicaciones , Retinopatía Diabética/tratamiento farmacológico , Humanos , Coagulación con Láser/métodos , Desprendimiento de Retina/tratamiento farmacológico , Desprendimiento de Retina/etiología , Neovascularización Retiniana/complicaciones , Neovascularización Retiniana/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
PURPOSE: To describe the clinical and multimodal imaging features of bacillary layer detachment (BD), and its response to intravitreal anti-vascular endothelial growth factor therapy, in eyes with macular neovascularization. METHODS: Retrospective, observational case series of 14 eyes (14 patients, 7 men) imaged with eyes (14 patients, 7 men) were imaged with spectral-domain optical coherence tomography, and either fluorescein angiography or optical coherence tomography angiography. Therapeutic response was monitored with serial imaging and best-corrected visual acuity assessments. RESULTS: The mean age was 75 ± 13 (range: 45-96) years, with mean follow-up duration of 27 ± 21 (range: 1-56) months. Neovascular age-related macular degeneration was found in 71% (10/14) eyes. Type 2 macular neovascularization lesions were associated with BD in all 14 eyes. Subretinal hemorrhage was noted in 79% (11/14) eyes. BD promptly resolved after intravitreal antivascular endothelial growth factor therapy in all eyes. The baseline best-corrected visual acuity improved from logarithm of the minimum angle of resolution 0.84 ± 0.32 (Snellen equivalent 20/138) to logarithm of the minimum angle of resolution 0.48 ± 0.31 (Snellen equivalent 20/60) at the last follow-up, with treatment of the macular neovascularization. CONCLUSION: Type 2 macular neovascularization and subretinal hemorrhage are associated with BDs, which may be due to a rapid influx of exudative fluid into the potential space between the external limiting membrane and ellipsoid zone. Intravitreal antivascular endothelial growth factor therapy results in rapid resolution of BDs and visual improvement in most eyes.
Asunto(s)
Desprendimiento de Retina/etiología , Neovascularización Retiniana/complicaciones , Segmento Interno de las Células Fotorreceptoras Retinianas/patología , Segmento Externo de las Células Fotorreceptoras Retinianas/patología , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Humanos , Inyecciones Intravítreas , Masculino , Persona de Mediana Edad , Imagen Multimodal , Desprendimiento de Retina/diagnóstico por imagen , Hemorragia Retiniana/inducido químicamente , Hemorragia Retiniana/diagnóstico por imagen , Hemorragia Retiniana/tratamiento farmacológico , Neovascularización Retiniana/diagnóstico por imagen , Neovascularización Retiniana/tratamiento farmacológico , Estudios Retrospectivos , Líquido Subretiniano , Tomografía de Coherencia Óptica , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Agudeza VisualRESUMEN
Diabetic retinopathy (DR) is a well-recognized microvascular complication of diabetes. Growing evidence suggests that, in addition to retinal vascular damage, there is significant damage to retinal neural tissue in DR. Studies reveal neuronal damage before clinically evident vascular lesions and DR is now classified as a neurovascular complication. Hyperglycemia causes retinal damage through complex metabolic pathways leading to oxidative stress, inflammation, vascular damage, capillary ischemia, and retinal tissue hypoxia. Retinal hypoxia is further worsened by high oxygen consumption in the rods. Persistent hypoxia results in increases in vascular endothelial growth factor (VEGF) and other pro-angiogenic factors leading to proliferative DR/macular edema and progressive visual impairment. Optimal glucose control has favorable effects in DR. Other treatments for DR include laser photocoagulation, which improves retinal oxygenation by destroying the high oxygen consuming rods and their replacement by low oxygen consuming glial tissue. Hypoxia is a potent stimulator of VEGF, and intravitreal anti-VEGF antibodies are effective in regressing macular edema and in some studies, retinal neovascularization. In this review, we highlight the complex pathophysiology of DR with a focus on retinal oxygen/fuel consumption and hypoxic damage to retinal neurons. We discuss potential mechanisms through which sodium-glucose cotransporter 2 (SGLT2) inhibitors improve retinal hypoxia-through ketone bodies, which are energetically as efficient as glucose and yield more ATP per molecule of oxygen consumed than fat, with less oxidative stress. Retinal benefits would occur through improved fuel energetics, less hypoxia and through the anti-inflammatory/oxidative stress effects of ketone bodies. Well-designed studies are needed to explore this hypothesis.
Asunto(s)
Retinopatía Diabética/tratamiento farmacológico , Hipoxia/prevención & control , Cetosis/inducido químicamente , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Animales , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patología , Retinopatía Diabética/metabolismo , Retinopatía Diabética/patología , Humanos , Cetosis/metabolismo , Cetosis/patología , Retina/efectos de los fármacos , Retina/metabolismo , Retina/patología , Neovascularización Retiniana/complicaciones , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Índice de Severidad de la Enfermedad , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacologíaRESUMEN
One of the commonly used models for ischemic retinopathies is the oxygen-induced retinopathy (OIR) model. Here we describe detailed protocols for the OIR model induction and its readouts in both mice and rats. Retinal neovascularization is induced in OIR by exposing rodent pups either to hyperoxia (mice) or alternating levels of hyperoxia and hypoxia (rats). The primary readouts of these models are the size of neovascular (NV) and avascular (AVA) areas in the retina. This preclinical in vivo model can be used to evaluate the efficacy of potential anti-angiogenic drugs or to address the role of specific genes in the retinal angiogenesis by using genetically manipulated animals. The model has some strain and vendor specific variation in the OIR induction which should be taken into consideration when designing the experiments.
Asunto(s)
Modelos Animales de Enfermedad , Isquemia/inducido químicamente , Oxígeno/farmacología , Enfermedades de la Retina/inducido químicamente , Animales , Isquemia/complicaciones , Ratones , Ratones Endogámicos C57BL , Ratas , Retina/efectos de los fármacos , Retina/metabolismo , Retina/fisiopatología , Enfermedades de la Retina/complicaciones , Neovascularización Retiniana/complicacionesRESUMEN
A 45-year-old male presented with diminution of vision in both eyes since the last 2 years. The best-corrected visual acuity was 20/200 in his right eye and 20/600 in left eye. BE fundi had changes of chronic CSCR with PED and NSD in the RE and subretinal fibrosis in the left eye. Both eyes had peripheral pigmentary changes. Multimodal imaging showed peripheral avascular retina in both eyes with neovascularization at disc in the right eye which promptly resolved with a single injection of anti-VEGF. Retinal neovascularization is an unusual finding in the setting of CSCR and has not been reported in the literature.
Asunto(s)
Coriorretinopatía Serosa Central , Neovascularización Retiniana , Coriorretinopatía Serosa Central/complicaciones , Coriorretinopatía Serosa Central/diagnóstico , Angiografía con Fluoresceína , Humanos , Masculino , Persona de Mediana Edad , Neovascularización Retiniana/complicaciones , Neovascularización Retiniana/diagnóstico , Tomografía de Coherencia Óptica , Agudeza VisualRESUMEN
BACKGROUND: Retinal neovascularization, which is characterized by the increased proliferation, migration, and tube formation of retinal microvascular endothelial cells (RMECs), contributes to the progression of diabetic retinopathy (DR). MiR-409-5p has been reported to be upregulated in peripheral blood of DR patients and in vascular endothelial growth factor (VEGF)-induced RMECs. However, the role of miR-409-5p in retinal neovascularization of DR remains unelucidated. METHOD: The expression of miR-409-5p was measured in retinal tissues of streptozocin-induced and db/db diabetic mice, in high glucose-induced mouse RMECs (mRMECs), and in vitreous fluid of proliferative DR patients. Antagomir of miR-409-5p was intravitreally injected into diabetic mice. Proliferation, migration, and tube formation were detected using cell counting kit-8 assay, transwell assay, and microscope observation, respectively. Luciferase reporter assay was used to detect the direct interaction between miR-409-5p and peroxisome proliferator-activated receptor-α (PPARα). RESULT: MiR-409-5p was upregulated in retinal tissues of diabetic mice, in high glucose-induced mRMECs, and in vitreous fluid of proliferative DR patients. The knockdown of miR-409-5p attenuated retinal neovascularization in vivo. The overexpression of miR-409-5p promotes the proliferation, migration, and tube formation, and increased VEGF expression and secretion, while the knockdown of miR-409-5p suppressed the VEGF-induced retinal neovascularization in vitro. PPARα is a downstream target of miR-409-5p, and PPARα overexpression negated the promotion of miR-409-5p overexpression on the proliferation, migration, and tube formation of mRMECs. CONCLUSION: Our findings demonstrated that miR-409-5p acted as a neovasculogenic factor in DR, and anti-miR-409-5p therapy may provide a novel strategy in treating DR.
Asunto(s)
Retinopatía Diabética/complicaciones , Retinopatía Diabética/genética , MicroARNs/metabolismo , Neovascularización Retiniana/complicaciones , Neovascularización Retiniana/genética , Animales , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células Endoteliales/patología , Técnicas de Silenciamiento del Gen , Glucosa/toxicidad , Masculino , Ratones Endogámicos C57BL , MicroARNs/genética , Microvasos/patología , PPAR alfa/metabolismo , Retina/patología , Regulación hacia Arriba/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: To report a case of a young patient with neurofibromatosis type 1 (NF1). METHODS: Here we review the treatment administered to a 7-year-old NF1 patient with neovascular glaucoma as the primary diagnosis. CASE PRESENTATION: A 7-year-old boy developed visual loss in the right eye associated with periocular pain and ipsilateral headache that had persisted for 1 week. The patient's condition did not improve after treatment with topical or systemic glaucoma medications. Fundus examination of the right eye showed superotemporal retinal vasoproliferative tumors (RVPT). Near-infrared reflectance scans of the left eye's fundus revealed bright patchy regions, scattered across the posterior pole; systemic examination showed café-au-lait spots all over the patient's body. The patient had a clear family history. Genetic testing confirmed NF1. The right eye was treated with intravitreal ranibizumab injection, retinal lesion cryotherapy, and transscleral ciliary body photocoagulation. After treatment, RVPT scarring was observed. The patient's intraocular pressure remained within normal limits. CONCLUSIONS: We report a rare case of neurofibromatosis in a pediatric patient with neovascular glaucoma accompanied by RVPT. We suggest that evaluations of young patients with neovascular glaucoma should include careful attention to the overall condition of the patient and his/her parents, as well as family history. If necessary, NF1 molecular testing should be performed to avoid a missed diagnosis or misdiagnosis.
Asunto(s)
Glaucoma Neovascular/etiología , Neurofibromatosis 1/complicaciones , Neoplasias de la Retina/complicaciones , Neovascularización Retiniana/complicaciones , Inhibidores de la Angiogénesis/uso terapéutico , Niño , Cuerpo Ciliar/cirugía , Angiografía con Fluoresceína , Glaucoma Neovascular/diagnóstico , Glaucoma Neovascular/cirugía , Humanos , Inyecciones Intravítreas , Coagulación con Láser , Masculino , Neurofibromatosis 1/diagnóstico , Neurofibromatosis 1/tratamiento farmacológico , Linaje , Ranibizumab/uso terapéutico , Neoplasias de la Retina/diagnóstico , Neoplasias de la Retina/tratamiento farmacológico , Neovascularización Retiniana/diagnóstico , Neovascularización Retiniana/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
Neovascular age-related macular degeneration (nAMD) is a complex and multi-factorial disease, and low-grade inflammation is associated with pathogenesis of nAMD. Aqueous humor could reflect intraocular immune environments in various eye diseases. The research so far used aqueous humor samples and revealed that inflammation is involved in pathophysiology of nAMD, although immunological roles of cytokines were evaluated inadequately with aspect to individual effects. Here we used 27 kinds of cytokines covering general immunologic reactions, examined specific expression patterns of cytokines, and assessed relationships between inflammation and pathophysiology of nAMD by multivariate analyses. In nAMD eyes, principal component analysis showed that IL-7, MCP-1, MIP-1ß and VEGF had high principal component loadings of over 0.6 in the first principal component constituting 32.6% of all variability of the data. In exploratory factor analysis, IL-6, MCP-1 and MIP-1ß had high factor loadings (FL) of over 0.5 in Factor 1 constituting 32.6% of all variability, while VEGF had FL of over 1.0 in Factor 3 constituting 10.7% of all variability. In hierarchical cluster analysis, MCP-1 and VEGF were located in the cluster of first proximate mutual distance to central retinal thickness. These data could suggest that low-grade inflammation is a principal contributor in nAMD.
Asunto(s)
Humor Acuoso/metabolismo , Neovascularización Coroidal/complicaciones , Citocinas/metabolismo , Degeneración Macular/inmunología , Neovascularización Retiniana/complicaciones , Anciano , Anciano de 80 o más Años , Humor Acuoso/inmunología , Neovascularización Coroidal/diagnóstico , Neovascularización Coroidal/inmunología , Citocinas/inmunología , Femenino , Angiografía con Fluoresceína , Perfilación de la Expresión Génica , Humanos , Degeneración Macular/diagnóstico , Degeneración Macular/patología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Retina/diagnóstico por imagen , Retina/inmunología , Retina/patología , Neovascularización Retiniana/diagnóstico , Neovascularización Retiniana/inmunología , Neovascularización Retiniana/patología , Vasos Retinianos/patología , Tomografía de Coherencia ÓpticaAsunto(s)
Neovascularización Coroidal/diagnóstico por imagen , Drusas del Disco Óptico/diagnóstico por imagen , Imagen Óptica , Neovascularización Retiniana/diagnóstico por imagen , Adolescente , Neovascularización Coroidal/complicaciones , Humanos , Masculino , Drusas del Disco Óptico/complicaciones , Neovascularización Retiniana/complicacionesRESUMEN
Pathologic posterior neovascularization of eye is a major cause of irreversible vision loss and limitations of therapeutics to be successfully delivered to back of the eye has been a main obstacle for its effective treatment. Current pharmacological treatment using anti-VEGF agents being delivered intravitreally are effective but complicated due to anatomical and physiological barriers, as well as administration of high and frequent doses. With expanding horizons of nanotechnology, it can be possible to formulate promising nanoscale delivery system to improve penetration and sustained the release of therapeutic in posterior segment of the eye. Taking into consideration advances in the field of nanoscale delivery systems, this special report focuses on emerging strategies and their applications for treatment of posterior ocular neovascularization.
Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Portadores de Fármacos/química , Nanopartículas/química , Neovascularización Retiniana/terapia , Adenoviridae/genética , Administración Oftálmica , Inhibidores de la Angiogénesis/farmacocinética , Animales , Ceguera/etiología , Ceguera/prevención & control , Barrera Hematoacuosa/metabolismo , Barrera Hematorretinal/metabolismo , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Terapia Genética/métodos , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Humanos , Terapia por Láser/métodos , Absorción Ocular , Permeabilidad , Fotoquimioterapia , Retina/metabolismo , Neovascularización Retiniana/complicaciones , Resultado del Tratamiento , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/genética , Baja Visión/etiología , Baja Visión/prevención & control , VitrectomíaRESUMEN
PURPOSE: To investigate the clinical significance of focal retinal pigment epithelium (RPE) atrophy in the eyes with type 3 neovascularization. METHODS: This retrospective study included 184 eyes those were diagnosed with type 3 neovascularization and were treated with antivascular endothelial growth factor (VEGF) therapy. Focal RPE atrophy was defined as a localized RPE atrophy found at the same location as the type 3 lesion. The incidence of reactivation after 3 loading injections and the visual outcomes was compared between a focal RPE atrophy group and a nonfocal RPE atrophy group. In the focal RPE atrophy group, the number of injections was compared between before and after the development of RPE atrophy. RESULTS: The mean follow-up period was 37.6 ± 18.8 months; focal RPE atrophy developed in 24 eyes (13.0%). Reactivation of the lesion after 3 loading injections was significantly less frequent in the focal RPE atrophy group (58.3%) than that in the nonfocal RPE atrophy group (85.0%) (P = 0.004). In the focal RPE atrophy group, the mean best-corrected visual acuity (BCVA) was 0.68 ± 0.28 (Snellen equivalent = 20/95) at diagnosis and 0.70 ± 0.48 (20/100) at the final follow-up. In the nonfocal RPE atrophy group, the values were 0.75 ± 0.34 (20/112) and 1.12 ± 0.68 (20/263), respectively. The BCVA at the final follow-up was significantly better in the focal RPE atrophy group (P < 0.001). The mean number of injections per year was 4.9 ± 1.8 and 1.3 ± 1.6 before and after the development of focal RPE atrophy, respectively (P < 0.001). CONCLUSIONS: Development of focal RPE atrophy was associated with a low incidence of reactivation of type 3 neovascularization and was therefore predictive of a favorable visual prognosis.
Asunto(s)
Degeneración Retiniana/diagnóstico , Neovascularización Retiniana/diagnóstico , Epitelio Pigmentado de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Agudeza Visual , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Atrofia/diagnóstico , Atrofia/tratamiento farmacológico , Atrofia/etiología , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Inyecciones Intravítreas , Masculino , Pronóstico , Ranibizumab/administración & dosificación , Degeneración Retiniana/tratamiento farmacológico , Degeneración Retiniana/etiología , Neovascularización Retiniana/complicaciones , Neovascularización Retiniana/tratamiento farmacológico , Estudios Retrospectivos , Factores de Tiempo , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
Feline neovascular vitreoretinopathy (FNV) is a newly recognized rare condition affecting kittens and young domestic cats. This study investigated the clinical and pathologic findings in 22 cats with FNV. In affected cats, ophthalmoscopy of the fundus (when visible) revealed avascular peripheral retinae and epiretinal vascular membranes. Frequent nonspecific clinical findings were buphthalmos ( n = 21), medically uncontrollable glaucoma ( n = 22), and lenticular abnormalities ( n = 13). Anterior segment dysgenesis (ASD) was detected clinically in affected cats ( n = 6). The fellow eye was affected in 11 of 18 cats to a variable degree or appeared clinically normal in 7 of 18 cats. The globes were examined histologically and using immunohistochemistry for vimentin, glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, laminin, factor VIII-related antigen (FVIII-RA), and smooth muscle actin (SMA). Histologically, diagnostic features included laminin-positive epiretinal vascular membranes affecting the central retina, with an avascular peripheral retina and gliosis. Enucleated globes exhibited multiple additional abnormalities, including corneal disease ( n = 15), anterior segment dysgenesis ( n = 21), lymphoplasmacytic anterior uveitis ( n = 19), peripheral anterior synechiae ( n = 20), retinal degeneration ( n = 22), and retinal detachment ( n = 19). Gliotic retinae labeled strongly for GFAP and vimentin with reduced expression of synaptophysin and neurofilament, consistent with degeneration or lack of differentiation. While an avascular peripheral retina and epiretinal fibrovascular membranes are also salient features of retinopathy of prematurity, there is no evidence to support hyperoxic damage in cats with FNV. The cause remains unknown.