Aflibercept Treatment for Neovascular Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy Refractory to Anti-vascular Endothelial Growth Factor

PURPOSE: To report the results of switching treatment to vascular endothelial growth factor (VEGF) Trap-Eye (aflibercept) in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) refractory to anti-VEGF (ranibizumab and bevacizumab). METHODS: This is a retrospective study involving 32 eyes from 29 patients; 18 were cases of neovascular AMD and 14 were cases of PCV. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) of spectral-domain optical coherence tomography were evaluated. RESULTS: BCVA and CMT improved from 0.58 to 0.55 (p = 0.005) and from 404 to 321 microm (p < 0.001), respectively, after switching to aflibercept. The 14 eyes that received 6 or more aflibercept injections remained stable at 0.81 to 0.81 and 321 to 327 microm (p = 1.0, 0.29), respectively, after 3 aflibercept injections. The 10 eyes that received 3 or more bevacizumab injections after 3 or more aflibercept injections worsened, from 0.44 to 0.47 and from 332 to 346 microm (p = 0.06, 0.05), respectively. The results showed similar improvement of BCVA and CMT in neovascular AMD and PCV. CONCLUSIONS: Aflibercept seems to be effective for improvement and maintenance of BCVA and CMT for neovascular AMD and PCV refractory to anti-VEGF. Switching from aflibercept back to bevacizumab treatment may not be a proper strategy.

The management of complicated glaucoma.

Complicated glaucomas present considerable diagnostic and management challenges. Response to treatment can be unpredictable or reduced compared with other glaucomas. However, target intraocular pressure and preservation of vision may be achieved with selected medical, laser and surgical treatment. The evidence for such treatment is expanding and consequently affords clinicians a better understanding of established and novel techniques. Herein we review the mechanisms involved in the development of complicated glaucoma and the current evidence supporting its management.

Evaluation of visual outcome of intravitreal injection avastin [bevacizumab] in proliferative diabetic retinopathy with vitreous hemorrhage

To report the visual outcome after intravitreal injection Avastin [Bevacizumab] in proliferative diabetic retinopathy with vitreous heamorrhage with 1 year followup. It was analytical observational type of study. The study was carried out at Eye department Abbasi Shaheed Hospital from July 2008-June 2010. 100 patients were selected through non-probability consecutive sampling technique from the diabetic eye clinic who presented with proliferative diabetic retinopathy and vitreous hemorrhage .Patients with vitreous hemorrhage in one eye and proliferative diabetic retinopathy or bilateral vitreous hemorrhage were included in the study. B scans were done in dense vitreous hemorrhage to exclude tractional retinal detachment. History was taken regarding duration of diabetes and decreased vision. Detailed ocular examination including visual aquity, intraocular pressure, detailed anterior segment examination on slitlamp and direct and indirect ophthalmoscopy was done. Other eye was also examined to exclude proliferative diabetic retinopathy in that eye. Patients were counselled for intravitreal injection Avastin [Bevacizumab]. After detailed examination patients were admitted in the ward and Intravitreal injection Avastin 1.25mg/0.05 ml was given in sterile environment in the operation theatre using fully aseptic technique. Patients were discharged on moxifloxacin eye drops and steroid antibiotic combination ointment at night time. Patients were followed up very next day, after 1 week, 6 weeks, 3 months, six months and 1 year. Snellens best corrected visul aquity was recorded at each visit along with fundus biomicroscopy and fundus flourescine angiography wherever possible. Other eye was also treated with intravitreal injection Avastin-[Bevacizumab], grid or focal laser treatment or panretinal fundus photocoagulation as and when required. 140 eyes of 100 patients were treated with intravitrea linjection Avastin [Bevacizumab] Followup ranged from 1st postoperative day to 1 year. Baseline visual aquity was PL/PR -perception of hand movement in 99 eyes, finger counting-6/60 in 27 eyes and 6/36 in 14 eyes. Improvement of vision was observed at 2 weeks. VA finger counting -6/60 was seen in 43 eyes, 6/36-6/18 in 63 eyes and there was no improvment in 14 eyes. After 6 month follow up FC-6/60 was seen in 18 eyes, 6/36-6/18 in 88 eyes, 6/12-6/9 was seen in 20 eyes. There was still no improvment in 14 eyes due to exudative maculopathyin 10 eyes and ischeamic maculopathy in 4 eyes. At one year followup VA finger counting-6/60 was seen in 14 eyes, 6/36- 6/18 in 87 eyes and 6/12-6/9 in 25 eyes. There was still no improvement in 14 eyes due to the above mentioned reasons. Vitreous hemorrhage resolved completely in 44 eyes, while 16 eyes had residual vitreous heamorrhage. Regression of neovascularization was observed in 120 eyes. Intravitreal injection Avastin [Bevacizumab] was repeated twice or thrice 6 weeks apart in patients with residual vitreous hemorrhage 11.4% [16 patients] and in patients with neovascularization at disc or elsewhere after 6 weeks of first injection30% [42 patients]. Some visual improvement was observed after repetition of the injection. Complications like cells in anterior chamber were seen in 5% of the eyes. Acute rise of intraocular pressure was seen in 15% eyes subconjunctival hemorrhage in 30% eyes. All the complications were managed successfully. It was concluded that Avastin is a promising drug for proliferative diabetic retinopathy. It is a very helping and simple procedure keeping in mind the long periods of absorption of vitreous hemorrhage and avoiding vitrectomy. Panretinal photocoagulation is recommended after clearance of vitreous hemorrhage

Case of Bilateral Retinal Neovascularization Associated with Chronic Idiopathic Myelofibrosis

We report a case of bilateral peripheral retinal neovascularization and chronic idiopathic myelofibrosis in a 69-year-old man. Ophthalmic examination revealed peripheral retinal nonperfusion with retinal neovascularization in both eyes and vitreous hemorrhage in the right eye. Fluorescein angiography of both eyes showed a marked midperipheral and peripheral avascular retina temporally with arteriovenous anastomosis and sea-fan neovascularizations. Blood tests showed pancytopenia and teardrop-shaped red blood cells, and bone marrow examination showed hypocellular marrow with severe fibrosis. The neovascularization was regressed following pars plana vitrectomy in the right eye and scatter laser photocoagulation in the left. The results suggest that peripheral retinal vessel occlusion and neovascularization may be associated with idiopathic myelofibrosis.

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.

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.

Retinal Angiomatous Proliferation and Intravitreal Bevacizumab Injection

PURPOSE: To evaluate the short-term efficacy and safety of intravitreal bevacizumab injection (IVBI) in patients with retinal angiomatous proliferation (RAP). METHODS: Seven eyes of 5 patients with RAP were included in this study. All of the eyes evidenced stage 2 RAP lesions, except for one eye with a stage 3 lesion. IVBI (1.25 mg/0.05 cc) were conducted at 4 or 6-week intervals. Complete ocular examinations, angiographic results and optical coherence tomographic findings before and after the IVBI were analyzed at baseline and upon the follow-up visits. RESULTS: Seven eyes were studied in 5 patients who had undergone IVBI. Partial (3 eyes) or complete (4 eyes) regression of RAP was noted after IVBI in all of the studied eyes. Visual acuity improved in 5 of the eyes, and was stable in 2 of the eyes. One eye evidenced severe intraocular inflammation after IVBI and a subsequent development of new RAP, which was controlled with vitrectomy and repeat IVBI. CONCLUSIONS: This treatment was effective over 6 months, stabilizing or improving visual acuity and reducing angiographic leakage. These short-term results suggest that IVBI may constitute a promising therapeutic option, particularly in the early stages of RAP.

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.