RESUMO
PURPOSE: There is an urgent need for treatments that prevent or delay development to advanced age-related macular degeneration (AMD). Drugs already on the market for other conditions could affect progression to neovascular AMD (nAMD). If identified, these drugs could provide insights for drug development targets. The objective of this study was to use a novel data mining method that can simultaneously evaluate thousands of correlated hypotheses, while adjusting for multiple testing, to screen for associations between drugs and delayed progression to nAMD. DESIGN: We applied a nested case-control study to administrative insurance claims data to identify cases with nAMD and risk-set sampled controls that were 1:4 variable ratio matched on age, gender, and recent healthcare use. PARTICIPANTS: The study population included cases with nAMD and risk set matched controls. METHODS: We used a tree-based scanning method to evaluate associations between hierarchical classifications of drugs that patients were exposed to within 6 months, 7 to 24 months, or ever before their index date. The index date was the date of first nAMD diagnosis in cases. Risk-set sampled controls were assigned the same index date as the case to which they were matched. The study was implemented using Medicare data from New Jersey and Pennsylvania, and national data from IBM MarketScan Research Database. We set an a priori threshold for statistical alerting at P ≤ 0.01 and focused on associations with large magnitude (relative risks ≥ 2.0). MAIN OUTCOME MEASURES: Progression to nAMD. RESULTS: Of approximately 4000 generic drugs and drug classes evaluated, the method detected 19 distinct drug exposures with statistically significant, large relative risks indicating that cases were less frequently exposed than controls. These included (1) drugs with prior evidence for a causal relationship (e.g., megestrol); (2) drugs without prior evidence for a causal relationship, but potentially worth further exploration (e.g., donepezil, epoetin alfa); (3) drugs with alternative biologic explanations for the association (e.g., sevelamer); and (4) drugs that may have resulted in statistical alerts due to their correlation with drugs that alerted for other reasons. CONCLUSIONS: This exploratory drug-screening study identified several potential targets for follow-up studies to further evaluate and determine if they may prevent or delay progression to advanced AMD.
Assuntos
Neovascularização de Coroide/diagnóstico , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos Genéricos/uso terapêutico , Degeneração Macular Exsudativa/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neovascularização de Coroide/prevenção & controle , Mineração de Dados , Progressão da Doença , Reposicionamento de Medicamentos/métodos , Feminino , Humanos , Revisão da Utilização de Seguros , Masculino , Medicare/estatística & dados numéricos , Estados Unidos , Degeneração Macular Exsudativa/prevenção & controleRESUMO
PURPOSE: To report the natural history of untreated neovascular age-related macular degeneration (nAMD) regarding subsequent macular atrophy. DESIGN: Prospective cohort within a randomized, controlled trial of oral micronutrient supplements. PARTICIPANTS: Age-Related Eye Disease Study (AREDS) participants (55-80 years) who demonstrated nAMD during follow-up (1992-2005), prior to anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Color fundus photographs were collected at annual study visits and graded centrally for late age-related macular degeneration (AMD). Incident macular atrophy after nAMD was examined by Kaplan-Meier analysis and proportional hazards regression. MAIN OUTCOME MEASURES: Incident macular atrophy after nAMD. RESULTS: Of the 4757 AREDS participants, 708 eyes (627 participants) demonstrated nAMD during follow-up and were eligible. The cumulative risks of incident macular atrophy after untreated nAMD were 9.6% (standard error, 1.2%), 31.4% (standard error, 2.2%), 43.1% (standard error, 2.6%), and 61.5% (standard error, 4.3%) at 2, 5, 7, and 10 years, respectively. This corresponded to a linear risk of 6.5% per year. The cumulative risk of central involvement was 30.4% (standard error, 3.2%), 43.4% (standard error, 3.8%), and 57.0% (standard error, 4.8%) at first appearance of atrophy, 2 years, and 5 years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.17-2.49; P = 0.006). However, higher 52-single nucleotide polymorphism AMD genetic risk score was not associated with increased risk of macular atrophy (HR, 1.03; 95% CI, 0.90-1.17; P = 0.67). Similarly, no significant differences were observed according to SNPs at CFH, ARMS2, or C3. CONCLUSIONS: The rate of incident macular atrophy after untreated nAMD is relatively high, increasing linearly over time and affecting half of eyes by 8 years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated nAMD suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, although a contribution remains possible. Central involvement is present in one third of eyes at the outset (similar to pure GA) and increases linearly to half at 3 years.
Assuntos
Neovascularização de Coroide/complicações , Atrofia Geográfica/epidemiologia , Degeneração Macular Exsudativa/complicações , Idoso , Idoso de 80 Anos ou mais , Antioxidantes/administração & dosagem , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Feminino , Seguimentos , Atrofia Geográfica/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Inquéritos e Questionários , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológico , Compostos de Zinco/administração & dosagemRESUMO
BACKGROUND: Previous case reports have demonstrated the occurrence of ischemic optic neuropathy (ION) following intravitreal injections of antivascular endothelial growth factor (anti-VEGF). However, no previous studies have investigated the impact of injection numbers on the risk of ION. The aim of our study was to investigate whether repeated intravitreal injections of anti-VEGF would increase the risk of subsequent ION in patients with neovascular age-related macular degeneration (AMD). METHODS: A population-based, retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from 2007 to 2013. Neovascular AMD patients receiving intravitreal injections of anti-VEGF during the study period were enrolled in the study cohort. Enrollees were divided into three groups according to the categorized levels of injection number (first level: < 10 times, second level: 10-15 times, and third level: > 15 times). Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent ION among the three groups. Cox regression analyses were used to estimate crude and adjusted hazard ratios (HRs) for ION development with respect to the different levels of injection numbers. The confounders included for adjustment were age, sex, and comorbidities (diabetes, hypertension, hyperlipidemia, ischemic heart disease, and glaucoma). RESULTS: In total, the study cohort included 77,210 patients. Of these, 26,520, 38,010, and 12,680 were in the first-, second-, and third-level groups, respectively. The Kaplan-Meier method revealed that the cumulative hazards of ION were significantly higher in those who had a higher injection number. After adjusting for confounders, the adjusted HRs for ION in the second- and third-level groups were 1.91 (95% confidence interval [CI], 1.32-2.76) and 2.20 (95% CI, 1.42-3.43), respectively, compared with those in the first-level group. CONCLUSIONS: Among patients with neovascular AMD, those who receive a higher number of anti-VEGF injections have a significantly higher risk of developing ION compared with individuals who receive a lower number of injections.
Assuntos
Inibidores da Angiogênese/efeitos adversos , Neovascularização de Coroide/tratamento farmacológico , Neuropatia Óptica Isquêmica/induzido quimicamente , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/diagnóstico , Bases de Dados Factuais , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Neuropatia Óptica Isquêmica/diagnóstico , Retratamento , Estudos Retrospectivos , Fatores de Risco , Taiwan , Tomografia de Coerência Óptica , Degeneração Macular Exsudativa/diagnósticoRESUMO
BACKGROUND AND OBJECTIVE: To evaluate a stereological method in optical coherence tomography (OCT) as an in vivo volume measurement of laser-induced choroidal neovascularization (L-CNV) lesion size. PATIENTS AND METHODS: Laser photocoagulation was applied in rats to rupture Bruch's membrane and induce L-CNV. In vivo OCT images of neovascular lesions were acquired with a spectral-domain OCT system at days 0, 3, 7, 10, and 14 after laser surgery. A stereological image-processing method was used to calculate lesion volumes from the OCT images. Rats were euthanized at day 14, and confocal microscopy was used to obtain accurate volume measurements of the lesions ex vivo. Lesion sizes calculated from OCT and confocal were compared. RESULTS: In vivo assessment by OCT allowed three distinct stages of L-CNV to be visualized: the initial early reaction, neovascular proliferation, and regression. At day 14, correlations between OCT and confocal lesion volumes showed a positive association (Pearson's r = 0.50, P < .01). Except for the largest lesions, volumes measured by OCT were statistically similar to those measured by the confocal gold standard (P = .90). CONCLUSION: The stereological approach used to measure neovascular lesion volume from OCT images offers an accurate means to track L-CNV lesion size in vivo. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e65-e74.].
Assuntos
Corioide/irrigação sanguínea , Neovascularização de Coroide/diagnóstico , Terapia com Luz de Baixa Intensidade/efeitos adversos , Tomografia de Coerência Óptica/métodos , Animais , Neovascularização de Coroide/etiologia , Modelos Animais de Doenças , Angiofluoresceinografia/métodos , Fundo de Olho , Degeneração Macular/diagnóstico , Degeneração Macular/cirurgia , Masculino , Ratos , Ratos Endogâmicos BNRESUMO
PURPOSE: To assess the value of 2-week optical coherence tomography (OCT) follow-up for re-treatment decision-making in patients receiving monthly ranibizumab injections for choroidal neovascular membrane (CNV), which was apparently refractory to treatment. METHODS: A total of 25 eyes of 25 consecutive patients with refractory CNV were included. Patients were classified as having refractory disease if no visual acuity (VA) change and no change in the pattern of macular fluid was noticed on OCT after at least 3 consecutive monthly injections, excluding the loading doses. Repeat injection was given and reassessment with VA and OCT was undertaken at 2, 4, 8, and 12 weeks. RESULTS: Complete resolution or marked reduction of macular fluid was noted in 19 patients at 2 weeks (responders). In 18 responders, the fluid increased on 4- and persisted on 8- and 12-week follow-ups, so that further injections were given at these time points. In 6 patients, no significant change was noted at 2 weeks (nonresponders). In all of them, VA and OCT were stable on 4-, 8-, and 12-week follow-ups, without further injections. CONCLUSIONS: As some patients are responding for at least part of the month, injections may be worth continuing or possibly more frequent injections, tailored to the individual's response, may need to be considered. Alternative therapies such as aflibercept may also need to be considered. In nonresponding eyes, other cytokines except for vascular endothelial growth factor are probably involved in the pathogenesis or such cases may have structural damage that will not respond to therapy.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Tomografia de Coerência Óptica , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/fisiopatologia , Corantes , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Verde de Indocianina , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Ranibizumab , Retratamento , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologiaRESUMO
A 30-year-old woman diagnosed with choroidal melanoma and treated with plaque radiation and transpupillary thermotherapy 5 years earlier presented with recalcitrant proliferative radiation retinopathy despite multiple intravitreal anti-vascular endothelial growth factor injections. Swept-source and spectral-domain optical coherence tomography (OCT) demonstrated intravitreal polyps lying on the surface of atrophied chorioretinal tissue. Fluorescein angiography (FA) revealed leakage from these saccular choroidal neovasculopathic vessels adjacent to a large zone of poor choroidal perfusion. Intravitreal polypoidal choroidal vasculopathy may be associated with radiation retinopathy and is well-demonstrated with swept-source and spectral-domain OCT and FA.
Assuntos
Neovascularização de Coroide/etiologia , Radioisótopos do Iodo/efeitos adversos , Pólipos/etiologia , Lesões por Radiação/etiologia , Retina/efeitos da radiação , Doenças Retinianas/etiologia , Adulto , Braquiterapia , Permeabilidade Capilar , Neoplasias da Coroide/radioterapia , Neovascularização de Coroide/diagnóstico , Feminino , Angiofluoresceinografia , Humanos , Hipertermia Induzida , Melanoma/radioterapia , Pólipos/diagnóstico , Lesões por Radiação/diagnóstico , Retina/patologia , Doenças Retinianas/diagnóstico , Tomografia de Coerência Óptica , Corpo Vítreo/patologiaRESUMO
PURPOSE: Spectral-domain optical coherence tomography (SD-OCT) is a noninvasive technique that can provide high-resolution images of macular morphology. The purpose of this study was to examine the pathological mechanism of uveitis and compare the changes in the macula of uveitis patients and the histopathological features of experimentally induced uveitis in mice. METHODS: Macular OCT was performed on 78 eyes of 51 patients of the Eye Hospital of Shandong University of Traditional Chinese Medicine, China, with apparent uveitis changes. C57BL/6 mice were injected with interphotoreceptor retinoid-binding protein (IRBP)-specific T cells from naïve mice immunized with complete Freund adjuvant IRBP(1-20) to induce uveitis. The disease was monitored by indirect fundoscopy. The eyes of the mice with experimental autoimmune uveitis (EAU) were enucleated 18 days after injection and classified according to pathological characteristics. RESULTS: The characteristics of uveitis were classified into six categories. Macular edema was detected in 48 eyes (61.5%); macular epiretinal membrane in 22 eyes (28.2%); choroidal neovascularization and macular lamellar holes in 4 eyes (5.1%), respectively; macular atrophy in 10 eyes (12.8%); and serous neuroepithelium detachment in 22 eyes (28.2%). As in human patients, pathological examinations of mouse EAU showed inflammation, folds, and atrophy of the outer part of the neuroretina, choroidal neovascularization with hemorrhagic retinal detachment, serous neuroepithelium detachment, and epiretinal membrane formation. CONCLUSIONS: Macular OCT of uveitis patients can display different morphological characteristics. Mouse EAU can simulate human uveitis. The comparative analysis of macular OCT in human uveitis and transfer EAU histopathology changes could provide important information on the pathogenesis of human uveitis.
Assuntos
Modelos Animais de Doenças , Macula Lutea/patologia , Tomografia de Coerência Óptica/métodos , Uveíte/diagnóstico , Transferência Adotiva , Adulto , Animais , Neovascularização de Coroide/diagnóstico , Membrana Epirretiniana/diagnóstico , Proteínas do Olho , Feminino , Angiofluoresceinografia , Humanos , Edema Macular/diagnóstico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Oftalmoscopia , Descolamento Retiniano/diagnóstico , Perfurações Retinianas/diagnóstico , Proteínas de Ligação ao Retinol , Linfócitos T/imunologia , Uveíte/imunologiaRESUMO
PURPOSE: To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms. METHODS: C57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)-1α in the RPE-choroid was determined by Western blotting. RESULTS: Curcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF-1α (P<0.05). CONCLUSION: Curcumin treatment led to the suppression of CNV development together with inflammatory and angiogenic processes including NF-κB and HIF-1α activation, the up-regulation of inflammatory and angiogenic cytokines, and infiltrating macrophages and granulocytes. This provides molecular and cellular evidence of the validity of curcumin supplementation as a therapeutic strategy for the suppression of age-related macular degeneration (AMD)-associated CNV.
Assuntos
Neovascularização de Coroide/prevenção & controle , Curcumina/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/patologia , Curcumina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Angiofluoresceinografia , Granulócitos/efeitos dos fármacos , Granulócitos/fisiologia , Macrófagos/efeitos dos fármacos , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Mandatory screening performed by an experience ophthalmologist remains the most important pillar in the management of retinopathy of prematurity (ROP). The current gold standard for treatment of proliferative ROP is still panretinal laser photocoagulation, depending on severity, in combination with vitreoretinal surgery if necessary. The first case series of off-label intravitreal anti-VEGF treatment are encouraging. In addition to intravitreal anti-VEGF therapy, other treatment concepts such as supplementation with IGF-1 or omega-3 fatty acids also represent interesting pharmacological approaches to the management of ROP. However, larger controlled trials are required to validate the benefits and safety of these systemic treatment approaches.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Fator de Crescimento Insulin-Like I/uso terapêutico , Retinopatia da Prematuridade/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Bevacizumab , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Terapia Combinada , Humanos , Recém-Nascido , Injeções Intravítreas , Fotocoagulação a Laser , Programas de Rastreamento , Uso Off-Label , Retinopatia da Prematuridade/diagnóstico , VitrectomiaRESUMO
BACKGROUND AND OBJECTIVE: To assess the safety and effectiveness of transpupillary thermotherapy treatment of subfoveal choroidal neovascular membrane secondary to pathologic myopia. PATIENTS AND METHODS: Seventy-four patients (74 eyes) with pathologic myopia underwent transpupillary thermotherapy treatment using a 3.0-mm spot size, 1-minute duration, and 520-mW power delivered through a contact lens. Clinical evaluation included measurement of best-corrected Snellen visual acuity, slit-lamp biomicroscopy, fundus color photography, and fluorescein angiography. RESULTS: Sixty-four eyes (86%) received one treatment session. Six eyes (8%) improved 0.1 logarithm of the minimum angle of resolution (LogMAR) visual acuity post-treatment, 10 eyes (13.5%) lost more than 0.2 LogMAR acuity, and another 10 eyes (13.5%) lost 0.1 LogMAR acuity. The remaining 48 eyes (65%) had unchanged visual acuity after the last follow-up visit. CONCLUSION: Transpupillary thermotherapy preserves vision in patients with choroidal neovascular membrane associated with pathologic myopia. Younger patients and eyes with higher refractive error are more likely to benefit from treatment.
Assuntos
Neovascularização de Coroide/terapia , Hipertermia Induzida/métodos , Miopia/complicações , Adulto , Idoso , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/etiologia , Feminino , Angiofluoresceinografia , Seguimentos , Fóvea Central , Fundo de Olho , Humanos , Masculino , Pessoa de Meia-Idade , Miopia/diagnóstico , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Acuidade VisualRESUMO
Choroidal neovascular membrane (CNVM) formation is a well-documented sight-threatening complication of posterior segment intraocular inflammation (PSII). The aim of this article is to review the basic and clinical science literature on the pathogenesis of CNVM formation in PSII and to present results of a case series. We searched the literature using the mesh terms- inflammation, CNVM, age-related macular degeneration, immunosuppression, photodynamic therapy, steroids, vascular endothelial growth factors and posterior uveitis. Additionally, we evaluated the visual outcome of and clinical response to our standard treatment protocol involving a combination treatment for young patients with inflammatory CNVM. The development of CNVM in PSII is promulgated by infiltrating myeloid cells as well as choroidal and retinal myeloid cell activation, subsequent vascular endothelial growth factors, cytokine and chemokine production and complement activation acting in consort to mediate angiogenic responses. No clear standard of care currently exists for the treatment of inflammatory CNVM and various combinations have been tried. Using our combination treatment, visual acuity improved in four, stabilized in one and worsened in four patients. Though significant advances have occurred in the understanding of the pathogenesis and management of this condition, optimizing therapeutic regimens will require further well-constructed prospective cohort series.
Assuntos
Neovascularização de Coroide , Glucocorticoides/uso terapêutico , Terapia de Imunossupressão/métodos , Fotocoagulação a Laser/métodos , Procedimentos Cirúrgicos Oftalmológicos/métodos , Fototerapia/métodos , Uveíte Posterior/complicações , Animais , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/etiologia , Neovascularização de Coroide/terapia , Humanos , PrognósticoRESUMO
BACKGROUND: To report a case of nonarteritic anterior ischemic optic neuropathy (NA-AION) following intravitreal injection of bevacizumab (Avastin). METHODS: Interventional case report with an 18-month follow-up. RESULTS: A 51-year-old male with pseudoxanthoma elasticum presented with NA-AION 2 weeks after treatment with intravitreal of bevazicumab (Avastin) for choroidal neovascularisation secondary to angioid streaks. Except from a small optic disc without cupping he did not show further risk factors. DISCUSSION: Risk of NA-AION should be taken into consideration when deciding for intravitreal application of drugs including anti-vascular endothelial growth factors (VEGF) agents like bevacizumab (Avastin) in the treatment of retinal vascular diseases.
Assuntos
Inibidores da Angiogênese/efeitos adversos , Estrias Angioides/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Neuropatia Óptica Isquêmica/induzido quimicamente , Pseudoxantoma Elástico/complicações , Estrias Angioides/diagnóstico , Anticorpos Monoclonais Humanizados , Arterite/induzido quimicamente , Bevacizumab , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/tratamento farmacológico , Angiofluoresceinografia , Seguimentos , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Neuropatia Óptica Isquêmica/diagnóstico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual , Corpo VítreoRESUMO
OBJECTIVE: To evaluate the pharmacologic activity and tolerability of JSM6427, a potent and first selective small-molecule inhibitor of integrin alpha5beta1, in monkey and rabbit models of choroidal neovascularization (CNV). METHODS: JSM6427 selectivity for alpha5beta1 was evaluated by in vitro binding assays while the ability of JSM6427 to inhibit CNV was investigated in a laser-induced monkey model and a growth factor-induced rabbit model. Intravitreal injections of JSM6427 (100, 300, or 1000 microg) or vehicle were administered immediately after the CNV induction procedure and at weekly intervals for 4 weeks. Fluorescein angiography was performed weekly. Ocular tolerability was evaluated ophthalmoscopically and histologically in both models; additional assessments in monkeys included electroretinography, biomicroscopy, pathological examination, and analysis of JSM6427 pharmacokinetics. RESULTS: JSM6427 was highly selective for the alpha5beta1-fibronectin interaction. Weekly intravitreal injections of JSM6427 resulted in a statistically significant dose-dependent inhibition of CNV in laser-induced and growth factor-induced models without any ocular JSM6427-related adverse effects. JSM6427 was cleared through the systemic circulation with no evidence of systemic accumulation. CONCLUSIONS: Intravitreal JSM6427 provided dose-dependent inhibition of CNV in monkey and rabbit experimental models. CLINICAL RELEVANCE: JSM6427 may provide a new approach for the treatment of ocular neovascular diseases such as age-related macular degeneration in humans.
Assuntos
Aminopiridinas/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Modelos Animais de Doenças , Integrina alfa5beta1/antagonistas & inibidores , beta-Alanina/análogos & derivados , Aminopiridinas/farmacocinética , Inibidores da Angiogênese/farmacocinética , Animais , Neovascularização de Coroide/diagnóstico , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Eletrorretinografia , Feminino , Fator 2 de Crescimento de Fibroblastos/antagonistas & inibidores , Angiofluoresceinografia , Injeções , Macaca fascicularis , Masculino , Coelhos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Corpo Vítreo , beta-Alanina/farmacocinética , beta-Alanina/uso terapêuticoRESUMO
The scientific background of laser photocoagulation of the ocular fundus was studied extensively by several investigators in the 1970 s and 1980 s. The basic principles were successfully resolved during that time and clinical consequences for proper application of the laser photocoagulation for various diseases were deduced. The present paper gives an overview about the physical basics of laser-tissue interactions during and after retinal laser treatment and the particular laser strategies in the treatment of different retinal diseases. Thus, it addresses the issue of the impact on tissue of laser parameters as wavelength, spot size, pulse duration and laser power. Additionally, the different biological tissue reactions after laser treatment are presented, such as, e. g., for retinopexia or macular treatments as well as for diabetic retinopathies. Specific laser strategies such as the selective laser treatment of the RPE (SRT) or the transpupillary thermotherapy (TTT) are presented and discussed.
Assuntos
Fotocoagulação/métodos , Doenças Retinianas/cirurgia , Corioide/patologia , Corioide/cirurgia , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/cirurgia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/cirurgia , Angiofluoresceinografia , Humanos , Macula Lutea/patologia , Macula Lutea/cirurgia , Oftalmoscopia , Papiledema/cirurgia , Epitélio Pigmentado Ocular/patologia , Epitélio Pigmentado Ocular/cirurgia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Retina/patologia , Retina/cirurgia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/cirurgia , Drusas Retinianas/cirurgia , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/cirurgiaRESUMO
We report a case of a choroidal neovascular membrane (CNVM) following ocular penetration during peribulbar anesthesia in a 55-year-old male patient. A combination of photodynamic therapy with intravitreal bevacizumab led to resolution of the persistent CNVM.
Assuntos
Anestesia Local/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Corioide/lesões , Neovascularização de Coroide/tratamento farmacológico , Ferimentos Oculares Penetrantes/tratamento farmacológico , Fotoquimioterapia , Anticorpos Monoclonais Humanizados , Bevacizumab , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/etiologia , Terapia Combinada , Ferimentos Oculares Penetrantes/diagnóstico , Ferimentos Oculares Penetrantes/etiologia , Angiofluoresceinografia , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Ferimentos Penetrantes Produzidos por Agulha/diagnóstico , Ferimentos Penetrantes Produzidos por Agulha/etiologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual , Corpo VítreoRESUMO
PURPOSE: To assess the macular retinal and choroidal microcirculation blood flow in patients with exudative age related macular degeneration before and after photodynamic therapy (PDT) or transpupillary thermotherapy (TTT) with Doppler laser scanning (HRF--Heidelberg retinal flowmeter). MATERIAL AND METHODS: Thirty patients with exudative age-related macular degeneration were included in a prospective study. The diagnosis was established based on ophthalmic examination and fluorescein angiography results. In all cases the subfoveal choroidal neovascularization (CNV) was present. Control group consists of the fellow eyes with early stage of AMD (19 eyes) or with disciform scar (11 eyes). In 15 eyes with active CNV PDT was performed and in remaining 15--TTT. In all cases the macular blood flow was measured with Heidelberg retina flowmeter (HRF) before therapy and then 1 week, 4 weeks and 10-12 weeks after treatment. RESULTS: At the baseline examination in a group of eyes with active CNV the mean values of macular blood flow were significantly higher comparing to the fellow eyes and reached respectively: 678.6 +/- 125.0 AU and 298.4 +/- 79.2 AU (p=0.001). Four weeks after treatment all eyes showed the reduction of macular blood flow comparing to the baseline values (p=0.001). Ten to twelve weeks after laser therapy in all cases the increased macular blood flow was detected comparing to the previous examination (p=0.01). During the follow-up period the macular blood flow in the fellow eyes were significantly lower than in treated eyes. CONCLUSIONS: The measurement of macular blood flow using Doppler scanning laser (HRF--Heidelberg retinal flowmeter) may act as a non-invasive and useful diagnostic tool in assessment of CNV activity in patients with exudative age-related degeneration before and after PDT or TTT.
Assuntos
Corioide/irrigação sanguínea , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/terapia , Macula Lutea/irrigação sanguínea , Degeneração Macular/terapia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neovascularização de Coroide/etiologia , Feminino , Angiofluoresceinografia , Humanos , Hipertermia Induzida , Fluxometria por Laser-Doppler , Degeneração Macular/complicações , Degeneração Macular/fisiopatologia , Masculino , Microcirculação , Pessoa de Meia-Idade , Fotoquimioterapia , Estudos Prospectivos , Fluxo Sanguíneo RegionalRESUMO
We demonstrated diagnostic cases of the early macular changes due to AMD, which caused central visual field disturbances. The aim of the study was to systemize the management in patients with macular lesions due to the age related macular degeneration, frequency determination and statement of the performed additional tests range. Patients reported central visual field distortions. We performed visual acuity testing, stereoscopic eye fundus examination, and PHP (macular visual field testing), which objectified distortions symptoms. Based on that tests and fellow eye condition, decision about OCT and FA and ICG performance were made. Further management was determined according to the results of that examinations: follow-up with vitamins and microelements supplementation or PDT. Our analysis confirm, that to monitor early macular changes due to AMD, follow-up examinations in 2-3 months interval are indicated: visual acuity testing, stereoscopic eye fundus examination and macular lesions modeling in PHP In difficult cases or in more advanced lesions FA, OCT and ICG were performed.
Assuntos
Neovascularização de Coroide/diagnóstico , Degeneração Macular/diagnóstico , Drusas Retinianas/diagnóstico , Idoso , Neovascularização de Coroide/etiologia , Feminino , Angiofluoresceinografia , Humanos , Macula Lutea , Degeneração Macular/complicações , Masculino , Pessoa de Meia-Idade , Oftalmoscopia/métodos , Drusas Retinianas/etiologia , Tomografia de Coerência Óptica , Acuidade Visual , Campos VisuaisRESUMO
AIM: The aim of the study was to compare the visual outcomes of photodynamic therapy (PDT) with verteporfin and transpupillary thermotherapy (TTT) for classic subfoveal choroidal neovascularization (CNVM) secondary to age-related macular degeneration (ARMD). SETTINGS AND DESIGN: Patients with subfoveal classic CNVM caused by ARMD attending vitreo-retinal services at a tertiary care setup were included in this nonrandomized, open label, prospective, clinical, comparative pilot trial. MATERIALS AND METHODS: Standardized refraction, visual acuity testing, evaluation of fundus and serial color photography and fundus fluorescein angiography were carried out to evaluate the effects of treatment in 32 eyes each undergoing either PDT or TTT. Follow-up was carried out at four weeks, 12 weeks and six months. Retreatment if indicated was carried out three months post treatment. RESULTS: Stabilization or improvement occurred in 69% of patients undergoing PDT and 50% patients undergoing TTT at six months of follow-up. Among patients with a pretreatment visual acuity greater than or equal to 20/63, only one out of six patients who underwent PDT had a drop of visual acuity > 2 lines as compared to four patients (100%) who underwent TTT. (P =0.0476, two-tailed Fisher's exact test). CONCLUSION: For short-term preservation of vision in patients of classic CNVM due to ARMD, PDT seems to be better than TTT if the pre-laser best corrected visual acuity is > 20/63 but both are equally effective if pre-laser best corrected visual acuity is < 20/63.
Assuntos
Neovascularização de Coroide/terapia , Hipertermia Induzida/métodos , Degeneração Macular/complicações , Fotoquimioterapia/métodos , Idoso , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/etiologia , Feminino , Angiofluoresceinografia , Seguimentos , Fundo de Olho , Humanos , Degeneração Macular/diagnóstico , Degeneração Macular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/uso terapêutico , Projetos Piloto , Porfirinas/uso terapêutico , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Verteporfina , Acuidade VisualRESUMO
BACKGROUND: To investigate the effect of transpupillary thermotherapy (TTT) on choroidal neovascularization (CNV) secondary to angioid streaks. METHODS: Six eyes of 5 patients with an average age of 61 years were diagnosed to have subfoveal CNV secondary to angioid streaks. Four of the CNVs were predominantly classic and 2 were occult with no classic. Visual acuity (VA) measurement, ophthalmoscopic and fluorescein angiographic examination, and optic coherence tomography (OCT) were carried out before TTT treatment and at each follow-up visit. Activity scores (AS) based on clinical, angiographic, and OCT findings were also recorded. RESULTS: The mean follow-up was 12 months. The VA initially ranged from counting fingers to 20/100 and remained stable in all patients. The mean greatest lesion diameter increased significantly from 2221 microm to 3109 microm at last follow-up (p=0.046). The mean AS decreased significantly from 6.5 to 4.8 at the 3rd month (p=0.039), but tended to increase thereafter. Retreatment with TTT was applied to 5 eyes after a mean of 7.8 months but did not decrease CNV activity as effectively as the first treatments. A fibrotic scar developed in 1 eye after the first treatment. INTERPRETATION: TTT may decrease the activity of CNVs secondary to angioid streaks in the short term, but retreatment may be necessary with unfavorable results. TTT appears to stabilize VA but not lesion size in this group of patients, which may be the natural history rather than a treatment effect.
Assuntos
Estrias Angioides/complicações , Neovascularização de Coroide/terapia , Hipertermia Induzida/métodos , Idoso , Neovascularização de Coroide/diagnóstico , Neovascularização de Coroide/etiologia , Feminino , Angiofluoresceinografia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pupila , Retratamento , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade VisualRESUMO
BACKGROUND: Photodynamic therapy with verteporfin (PDT) significantly reduces the risk of vision loss in patients with exudative age-related macular degeneration (AMD). Indocyanine green-mediated photothrombosis (IMP) and trans-pupillary thermotherapy (TTT) may also be beneficial for selective cases of exudative AMD. However, a substantial subset of patients responds poorly to these treatments. Intravitreal bevacizumab (IVB) has been recently used in the treatment of exudative AMD, showing both visual and anatomic improvement in the majority of cases. METHODS: This interventional retrospective case series reports the effects of IVB in 17 eyes with subfoveal neovascular AMD that had undergone repeated PDT (combined or not with triamcinolone acetonide) or PDT followed by either IMP or TTT with poor results. The main outcome measures were visual acuity and tomographic signs of intra/subretinal fluid, as well as central retinal thickness. RESULTS: Most patients received a single IVB injection. The mean follow-up was 4.47 months. The mean logMAR visual acuity changed from 1.17 +/- 0.40 to 1.06 +/- 0.44 (P = 0.17). The mean central retinal thickness decreased from 404.05 +/- 245.26 to 280.23 +/- 143.14 microm (P = 0.032). At the end of the study, lack of tomographic signs of intra/ subretinal fluid was noted in four (23.5%) eyes. No ocular or systemic side effects were identified. CONCLUSIONS: Short-term results with IVB for the treatment of exudative AMD have been promising. However, the chronic retinal and pigment epithelium changes frequently present in eyes that underwent multiple previous treatments may limit complete visual recovery. To our knowledge, this is the first report on the use of IVB for this particular group of AMD patients.