siRNA knockdown of angiopoietin 2 significantly reduces neovascularization in diabetic rats.

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.

Early pars plana vitrectomy for proliferative diabetic retinopathy: update and review of current literature.

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.

Intravitreal bevacizumab for peripapillary subretinal neovascular membrane associated to papilledema: a case report.

The purpose of this report is to document the use of bevacizumab as treatment of peripapillary subretinal neovascular membrane associated to idiopathic intracranial hypertension. This case reports a 31-year-old obese female with chronic papilledema due to idiopathic intracranial hypertension that developed an acute submacular hemorrhage due to a choroidal neovascular membrane in her left eye. Two separate intravitreal injections of bevacizumab (1.25 mg/0.5 ml) were administered with six weeks apart. Fourteen weeks after the initial injection her visual acuity improved to 20/40 in her left eye with associated angiographic resolution of the hemorrhage. Bevacizumab appears to be an effective option for patients who have subretinal neovascular membranes due to papilledema. Although choroidal neovascularization may have different pathogenic mechanisms, our case report demonstrates encouraging results without adverse ocular or systemic side effects.

Intermediate uveitis complicated by choroidal granuloma following subretinal neovascular membrane: case reports / Granuloma de coróide secundário a membrana neovascular sub-retiniana em uveíte intermediária: relato de casos

Choroidal neovascularization is a very rare complication in intermediate uveitis. A 27-year-old female patient diagnosed with intermediate uveitis two years ago. She presented with 20/200 visual acuity, snowballs, snowbanks, and macular cystoid edema in the right eye observed by fluorescein and optical coherence tomography (OCT). Photocoagulation was performed in the inferior peripheral retina in both eyes. The patient refused to undergo the prescribed clinical treatment. She returned twelve months later presenting with count fingers visual acuity, dry retina and subretinal macular pigmented granuloma observed on OCT. A 15-year-old female patient with decreased visual acuity of 20/400 in the right eye for eight days. She presented with bilateral vasculitis and papilitis, in the right eye, hemorrhage and extramacular subretinal neovascular membrane were observed on fluorescein and OCT. She was treated with 40 mg prednisone and intravitreous injection of 1.25 mg bevacizumab. Five months later she presented with 20/50 visual acuity, and extramacular granuloma observed on OCT. The formation of subretinal granuloma in intermediate uveitis is a possibility when complicated by subretinal neovascular membrane.

Neovascularização de coróide é uma complicação muito rara na uveíte intermediária(1). Paciente feminino, 27 anos, com diagnóstico de uveíte intermediária dois anos atrás. Apresentava acuidade visual de 20/200, "snowballs", "snowbanks" e edema macular cistóide no olho direito observado na angiofluoresceinografia (AGF) e tomografia de coerência óptica (OCT). Fotocoagulação foi realizada na retina periférica inferior em ambos os olhos. A paciente recusou a submeter-se ao tratamento clínico prescrito. Ela retornou doze meses mais tarde apresentando acuidade visual de conta dedos, retina sem edema e granuloma sub-retiniano macular observado no OCT(2). Paciente feminino, 15 anos, com diminuição da acuidade visual no olho direito (20/400) há oito dias. Apresentava vasculite e papilite em ambos os olhos, no olho direito, hemorragia e membrana neovascular sub-retiniana observada na AGF e OCT. Foi tratada com 40 mg de prednisona e injeção intra-vítreo de bevacizumab (1,25 mg). Cinco meses depois, apresentou acuidade visual de 20/50 e granuloma extramacular observada no OCT. A formação de granuloma sub-retiniano na uveíte intermediária é uma possibilidade quando complicada por membrana neovascular sub-retiniana.

Intermediate uveitis complicated by choroidal granuloma following subretinal neovascular membrane: case reports.

Choroidal neovascularization is a very rare complication in intermediate uveitis. A 27-year-old female patient diagnosed with intermediate uveitis two years ago. She presented with 20/200 visual acuity, snowballs, snowbanks, and macular cystoid edema in the right eye observed by fluorescein and optical coherence tomography (OCT). Photocoagulation was performed in the inferior peripheral retina in both eyes. The patient refused to undergo the prescribed clinical treatment. She returned twelve months later presenting with count fingers visual acuity, dry retina and subretinal macular pigmented granuloma observed on OCT. A 15-year-old female patient with decreased visual acuity of 20/400 in the right eye for eight days. She presented with bilateral vasculitis and papilitis, in the right eye, hemorrhage and extramacular subretinal neovascular membrane were observed on fluorescein and OCT. She was treated with 40 mg prednisone and intravitreous injection of 1.25 mg bevacizumab. Five months later she presented with 20/50 visual acuity, and extramacular granuloma observed on OCT. The formation of subretinal granuloma in intermediate uveitis is a possibility when complicated by subretinal neovascular membrane.

[Angiogenesis and retinal diseases]. / Angiogênese e doenças da retina.

Angiogenesis is the process involving the growth of new blood vessels from preexisting vessels which occurs in both physiologic and pathological settings. It is a complex process controlled by a large number of modulating factors, the pro-and antiangiogenic factors. The underlying cause of vision loss in proliferative retinal diseases, such as age-related macular degeneration and proliferative diabetic retinopathy, are increased vascular permeability and choroidal neovascularization, and vascular endothelial growth factor (VEGF) plays a central role in this process. VEGF is produced in the eye by retinal pigment epithelium (RPE) cells and is upregulated by hypoxia. There are four major biologically active human isoforms, of which VEGF165 is the predominant in the human eye and appears to be the responsible for pathological ocular neovascularization. Besides being a potent and specific mitogen for endothelial cells, VEGF increases vascular permeability, inhibits endothelial cells apoptosis, and is a chemoattractant for endothelial cell precursors. VEGF is not the only growth factor involved in ocular neovascularization. Basic fibroblast growth factor (bFGF), angiopoietins, pigment epithelium-derived factor (PEDF), and adhesion molecules also play a role in the pro- and antiangiogenic balance. Advances in the understanding of the bases of pathological ocular angiogenesis and identification of angiogenesis regulators have enabled the development of novel therapeutic agents. Anti-VEGF antibodies have been developed for intravitreal use, and other approaches are currently under investigation. These new drugs may be powerful tools for the treatment of the leading causes of irreversible blindness in people over age 65.

Angiogênese e doenças da retina / Angiogenesis and retinal diseases

Angiogênese é o processo de formação de vasos sangüíneos a partir de vasos preexistentes, que ocorre em condições fisiológicas e patológicas. É fenômeno complexo no qual participam inúmeras moléculas que estimulam e inibem a formação dos neovasos. O aumento da permeabilidade vascular e a neovascularização sub-retiniana são as causas da perda visual nas doenças proliferativas da retina, como a degeneração macular relacionada à idade e a retinopatia diabética, e o fator de crescimento do endotélio vascular ("vascular endothelial growth factor", VEGF) desempenha um papel muito importante nesse processo. Existem quatro isoformas da molécula de VEGF biologicamente ativas em seres humanos, das quais o VEGF165 é a isoforma predominante no olho humano, e existem evidências de que seja a isoforma responsável pela neovascularização patogênica no olho. Além de ser potente mitógeno de células endoteliais, o VEGF aumenta a permeabilidade vascular, inibe a apoptose das células endoteliais e promove migração de precursores de células endoteliais. O VEGF não é a única molécula cuja expressão está aumentada na angiogênese patológica. O fator de crescimento de fibroblasto ("basic fibroblast growth factor", bFGF), as angiopoetinas, o fator derivado do epitélio pigmentado ("pigment epithelium-derived factor", PEDF) e os fatores de adesão relacionados à matriz extracelular também exercem papel importante no balanço entre fatores pró- e antiangiogênicos. Todo o conhecimento adquirido sobre o mecanismo da angiogênese ocular patológica tem possibilitado o desenvolvimento de vários inibidores desse processo. Atualmente existem dois anticorpos anti-VEGF para uso intravítreo e outras abordagens terapêuticas do bloqueio da angiogênese ocular estão em fase de desenvolvimento. As novas drogas deverão ser armas poderosas no tratamento das principais causas de cegueira legal irreversível em indivíduos com mais de 65 anos.

Angiogenesis is the process involving the growth of new blood vessels from preexisting vessels which occurs in both physiologic and pathological settings. It is a complex process controlled by a large number of modulating factors, the pro-and antiangiogenic factors. The underlying cause of vision loss in proliferative retinal diseases, such as age-related macular degeneration and proliferative diabetic retinopathy, are increased vascular permeability and choroidal neovascularization, and vascular endothelial growth factor (VEGF) plays a central role in this process. VEGF is produced in the eye by retinal pigment epithelium (RPE) cells and is upregulated by hypoxia. There are four major biologically active human isoforms, of which VEGF165 is the predominant in the human eye and appears to be the responsible for pathological ocular neovascularization. Besides being a potent and specific mitogen for endothelial cells, VEGF increases vascular permeability, inhibits endothelial cells apoptosis, and is a chemoattractant for endothelial cell precursors. VEGF is not the only growth factor involved in ocular neovascularization. Basic fibroblast growth factor (bFGF), angiopoietins, pigment epithelium-derived factor (PEDF), and adhesion molecules also play a role in the pro- and antiangiogenic balance. Advances in the understanding of the bases of pathological ocular angiogenesis and identification of angiogenesis regulators have enabled the development of novel therapeutic agents. Anti-VEGF antibodies have been developed for intravitreal use, and other approaches are currently under investigation. These new drugs may be powerful tools for the treatment of the leading causes of irreversible blindness in people over age 65.

Estrias angióides - relato de um caso com duas membranas neovasculares num mesmo olho, documentado com indocianina verde / Angioid streaks - a documented case using indocyanine green with two choroidal neovascularization in the same eye

Objetivo: Apresentar um caso de estrias angióides com duas membranas neovasculares num mesmo olho, documentado com indocianina verde. Local: Setor de Retina e Vítreo do Departamento de Oftalmologia da Santa Casa de São Paulo. Método: Avaliação angiográfica retínica com indocianina verde. Resultado: Na avaliação angiográfica com indocianina verde, encontramos duas membranas neovasculares no olhos esquerdo. Conclusão: Utilizando angiografia retínica com indocianina verde, em estrias angióides, foi possível detectar mais de uma membrana num mesmo olho.

Ocular findings in sickle cell patients on Curaçao.

We examined about half the estimated number (based on gene frequency) of sickle cell patients on the island of Curaçao. This study may represent one of the most comprehensive and a selective cross-sectional surveys available. Studying 81 Hb SS and 97 Hb SC patients, we were able to confirm the correlation between iris atrophy and proliferative sickle retinopathy (PSR), the correlation between Hb SC and proliferative sickle retinopathy (PSR) and the major role of PSR in blindness in sickle cell patients. In Hb SC patients over the age of 18 PSR occurred in 50%, leading to vitreous hemorrhage in 18% and to retinal detachment in 8%. We found a frequency of blindness in one eye (fingers counting or less) of 4% in the entire sickle population, and 6% among Hb SC patients. Bilateral blindness was rare: one Hb SS patient, due to cortical blindness. The relatively frequent occurrence of severe complications in a narrowly defined population should stimulate our efforts to prevent these from occurring.