Degeneração macular relacionada à idade: o potencial terapêutico das células-tronco / Age-related macular degeneration: the therapeutic potential of stem cells

Introdução: A degeneração macular relacionada à idade (DMRI) é uma patologia ocular crônico-degenerativa com perda progressiva e irreversível da visão central. Os avanços no campo da pesquisa das células-tronco têm voltado suas atenções para a aplicação da terapia celular com o intuito de regenerar tecidos oculares que são danificados por essa doença. A DMRI exsudativa possui terapia com anti-fator de crescimento endotelial vascular, e a DMRI seca ou atrófica, não possui terapia aprovada disponível. Objetivo: Avaliar o potencial terapêutico do uso de células-tronco no tratamento de DMRI seca por meio de estudos que demonstraram a segurança e eficácia de experimentos com injeções intravítreas de fração mononuclear da medula óssea contendo células CD34+. Métodos: Revisão da literatura em artigos entre 2009 e 2017, usando como base os bancos de dados Scielo, PubMed e Lilacs. Resultado: Estudos evidenciaram que o uso de injeções intravítreas de fração mononuclear da medula óssea contendo células-tronco CD34+ está associado com melhora significativa da acuidade visual e do limiar de sensibilidade macular. Ademais, a ausência de crescimento tumoral, desenvolvimento de neovascularização coroidal, a não associação com inflamação significativa e o não comprometimento da função visual demonstrou a segurança da utilização da terapia. Conclusão: Os avanços nos estudos demonstraram que o uso da terapia celular na DMRI atrófica acarreta melhora da visão, proporcionando melhor qualidade de vida. Por isso, verifica-se a necessidade do investimento em novas pesquisas para ampliar os testes e confirmar se esta abordagem de tratamento será realmente eficaz e bem tolerada. (AU)

Introduction: Age-related macular degeneration (AMD) is a chronic degenerative eye condition with progressive and irreversible loss of central vision. Advances in the field of stem cell research have focused on the application of cell therapy in order to regenerate eye tissues that are damaged by this disease. Exudative AMD has anti-vascular endothelial growth factor therapy, and dry or atrophic AMD has no approved therapy available. Objective: To evaluate the therapeutic potential of stem cell use in the treatment of dry AMD through studies demonstrating the safety and efficacy of experiments with intravitreal injections of mononuclear bone marrow fraction containing CD34 + cells. Methods: Literature review in articles between 2009 and 2017, using as basis the databases Scielo, PubMed and Lilacs. Results: Studies have shown that the use of intravitreal injections of mononuclear bone marrow fraction containing CD34 + stem cells is associated with significant improvement in visual acuity and macular sensitivity threshold. In addition, the absence of tumor growth, development of choroidal neovascularization, non-association with significant inflammation and non-impairment of visual function demonstrated the safety of therapy use. Conclusion: Advances in studies have shown that the use of cell therapy in atrophic AMD causes improved vision, providing better quality of life. Therefore, it is necessary to invest in new research to expand the tests and confirm if this treatment approach will be really effective and well tolerated. (AU)

Use of Fundus Autofluorescence Images to Evaluate the Progression of Geographic Atrophy: Two-Year Follow-Up Study

PURPOSE: We evaluated the progression of geographic atrophy (GA) based on fundus autofluorescence (FAF) pattern and atrophy size using the fundus camera in non-exudative age-related macular degeneration (ARMD). METHODS: We acquired FAF images in non-exudative ARMD patients over a 2-year period. According to The Fundus Autofluorescence in Age-related Macular Degeneration (FAM) study, FAF patterns of geographic atrophy were classified into 5 categories. Examiners quantified the areas of GA in FAF images and analyzed the progression of atrophy based on FAF pattern and atrophy size. RESULTS: In 86 non-exudative ARMD eyes, elderly patients had faster progression rate of GA. The growth rates of GA were 1.51 mm2/year in 'Diffuse', 1.49 mm2/year in 'Banded', 1.05 mm2/year in 'Patchy', 0.59 mm2/year in 'Focal' and 0.16 mm2/year in 'None' pattern groups. In addition, the growth rate was 0.38 mm2/year in which initial the GA area was smaller than 1 disc area. This was the slowest progression rate among all categories according to initial GA area. CONCLUSIONS: As a result of evaluating the progression of geographic atrophy using FAF over a 2-year period, the growth rate of GA was the fastest in the 'Diffuse' pattern group. Additionally, as the initial GA area became smaller, the progression of GA atrophy was slower (p < 0.002). Although limitations such as short follow-up period and measurement error of GA atrophy area using fundus photography were compensated, the results in the present study were similar to the outcomes of studies on progression of GA based on FAF pattern using the scanning laser ophthalmoscope over several years and the fundus camera for 1 year. In conclusion, the fundus camera is a useful tool for the prediction of long-term progression of GA in patients with non-exudative ARMD.

Comparison of Retinal Nerve Fiber Layers in Patients with Non-Neovascular Age-Related Macular Degeneration and Normal Controls

PURPOSE: In neovascular age-related macular degeneration (AMD), it is reported that retinal nerve fiber layer (RNFL) thickness becomes gradually thinner due to degeneration of the outer retinal layer. To our knowledge, there is no previous report regarding RNFL thickness in patients with non-neovascular AMD. Therefore, in this study, we compared RNFL thickness in patients with non-neovascular AMD and normal controls. METHODS: Thirty-one eyes with AMD category 3a (AREDS research group), 11 eyes suffering foveal geographic atrophy AMD category 4a, and 31 age-matched normal eyes were evaluated. In every group, regional RNFL thickness (General, Temporal, Superotemporal, Superonasal, Superior, Nasal, Inferonasal, Inferotemporal, and Inferior) was measured using spectral domain optical coherence tomography (SD-OCT). RESULTS: There were no significant differences in age or intraocular pressure among the 3 groups. The mean best corrected visual acuity (BCVA) (log MAR) of the category 4a group was significantly decreased compared to those of the other 2 groups. The mean RNFL thickness in total area in the category 3a group, category 4a group, and normal control group was 99.5 +/- 14.0 microm, 99.3 +/- 9.4 microm, and 99.4 +/- 9.6 microm, respectively. The difference was not statistically significant. No other regional mean values of RNFL thickness in the three groups were significantly different. CONCLUSIONS: There was no significant difference in RNFL thickness between non-neovascular patients and the control group.

Age-related macular degeneration with choroidal neovascularization in the setting of pre-existing geographic atrophy and ranibizumab treatment. Analysis of a case series and revision paper / Avaliação da resposta da injeção intravítrea de ranibizumab em pacientes com neovascularização de coróide da degeneração macular relacionada à idade com atrofia geográfica extensa pré-existente e revisão da literatura

PURPOSE: To report the response of choroidal neovascularization (CNV) to intravitreal ranibizumab treatment in the setting of age-related macular degeneration (AMD) with extensive pre-existing geographic atrophy (GA) and a revision paper. METHODS: This is a revision paper and a retrospective case series of 10 eyes in nine consecutive patients from a photographic database. The patients were actively treated with ranibizumab for neovascular AMD with extensive pre-existing GA. Patients were included if they had GA at or adjacent to the foveal center that was present before the development of CNV. The best corrected visual acuity and optical coherence tomography (OCT) analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab were administered until there was resolution of any subretinal fluid clinically or on OCT. Data over the entire follow-up period were analyzed for overall visual and OCT changes. All patients had been followed for at least 2 years since diagnosis. RESULTS: The patients received an average of 6 ± 3 intravitreal injections over the treatment period. Eight eyes had reduced retinal thickening on OCT. On average, the central macular thickness was reduced by 94 ± 101 µm. Eight eyes had improvement of one or more lines of vision, where as one eye had dramatic vision loss and one had no change. The average treatment outcome for all patients was -0.07 ± 4.25 logMAR units, which corresponded to a gain of 0.6 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with the disappearance of the subretinal fluid, improved visual acuity, and stabilized final visual results. CONCLUSION: The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF) agent (ranibizumab) for CNV in AMD with extensive pre-existing GA is effective. Our results are not as striking as published results from large-scale trials of anti-VEGF therapy for subfoveal CNV, presumably due to the limitation in the baseline visual acuity caused by the underlying GA. The good anatomic response with the disappearance of the subretinal fluid, improved visual acuity, and stabilized final visual results were consistent with other ranibizumab studies.

Investigar os resultados da injeção intravítrea de Ranibizumab em pacientes com neovascularização de coróide da degeneração macular relacionada a idade, com atrofia geográfica extensa, pré-existente e revisão da literatura. MÉTODOS: Este é um artigo de revisão e também um estudo retrospectivo de 9 pacientes, 10 olhos com neovascularização de coróide da degeneração macular relacionada à idade, com atrofia geográfica extensa, pré-existente. Os pacientes incluídos apresentaram atrofia geográfica, envolvendo a fóvea ou adjacente, antes do desenvolvimento da neovascularização de coróide. A melhor correção visual e o exame de tomografia de coerência óptica (OCT) com analise da espessura macular foram registrados em cada visita. As injeções de ranibizumab intravítrea foram feitas até a resolução do líquido sub-retiniano pelo OCT e clinicamente. Todos os pacientes tinham seguimento de 6 meses do diagnostico a 2 anos, com média de 16 meses. RESULTADOS: 10 olhos de 9 pacientes incluídos receberam uma média de 6 ± 3 injeções intravítreas de ranibizumab, sendo que 8 apresentaram redução do espessamento macular pelo OCT. A mácula teve o espessamento reduzido entre 94 ± 101 microns, 8 olhos tiveram melhora de 1 ou mais linhas de visão, um olho teve acentuada diminuição da visão.e um outro não teve alteração. A media do resultado do tratamento em logMAR era -0,07 ± 4.25 correlacionando um ganho de visão na tabela de Snellen entre 0,6 ± 4.4linhas de visão. CONCLUSÃO: Estes resultados sugerem que o uso do Ranibizumab intravítreo para neovascularização de coróide da degeneração macular relacionada à idade em extensa atrofia geográfica pré-existente é efetivo. Existem, entretanto, dificuldades na avaliação da acuidade visual destes pacientes em virtude da extensa Atrofia Geográfica que apresentavam e sobre esta ainda as complicações da neovascularização de coróide, se comparados a casos em que a neovascularização de coróide não ocorre em atrofia geográfica pré-existente.

Intravitreal ranibizumab and bevacizumab therapy for choroidal neovascularization in age-related macular degeneration with extensive pre-existing geographic atrophy / Avaliação da resposta da injeção intravítrea de ranibizumab e bevacizumab em pacientes com neovascularização de coroide da degeneração macular relacionada à idade com atrofia geográfica extensa pré-existente

PURPOSE: To report the response of choroidal neovascularization to intravitreal ranibizumab or bevacizumab treatment in the setting of age-related macular degeneration with extensive pre-existing geographic atrophy of the retinal pigment epithelium. METHODS: This is a retrospective case series of 11 eyes in ten consecutive patients retrieved from a photographic database. The patients were treated with ranibizumab or bevacizumab for neovascular age-related macular degeneration with pre-existing geographic atrophy. Patients were included if they had geographic atrophy at or adjacent to the foveal center of at least 1 disc area in size that was present before the development of choroidal neovascularization. The best corrected visual acuity and optical coherence tomography analysis of the central macular thickness were recorded for each visit. Serial injections of ranibizumab or bevacizumab were administered until there was complete resolution of subretinal fluid on optical coherence tomography. Data over the entire follow-up period were analyzed for overall visual and optical coherence tomography changes. RESULTS: The patients received an average of 7 ± 3 intravitreal injections over the treatment period. Seven of 11 eyes had reduced retinal thickening on optical coherence tomography. On average, the central macular thickness was reduced by 72 ± 115 µm. Six of these 7 eyes had improvement of one or more lines of vision and one had no change. The average acuity change for all patients was -0.04 ± 0.46 logMAR units, which corresponded to a gain of 0.2 ± 4.4 lines of Snellen acuity. The treatment resulted in a good anatomic response with resolution of the subretinal fluid and overall stable visual acuity. CONCLUSIONS: The results of this case series suggest that the use of an intravitreal anti-vascular endothelial growth factor (VEGF) agent (ranibizumab or bevacizumab) for choroidal neovascularization in age-related macular degeneration with pre-existing geographic atrophy is effective. Our results are not as striking as published results from large-scale trials of anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization, presumably due to the limitation in the baseline visual acuity caused by the underlying geographic atrophy. The favorable anatomic response with the resolution of subretinal fluid and stable acuity were consistent with other ranibizumab and bevacizumab studies.

OBJETIVO: Avaliação dos resultados da injeção intravítrea de ranibizumab e bevacizumab em pacientes com neovascularização de coróide da degeneração macular relacionada a idade, com atrofia geográfica extensa, pré-existente. MÉTODOS: Este é um estudo retrospectivo de 10 pacientes, 11 olhos com neovascularização de coroide da degeneração macular relacionada à idade, com atrofia geográfica extensa, pré-existente. Os pacientes incluídos apresentaram atrofia geográfica, envolvendo a fóvea ou adjacência, antes do desenvolvimento da neovascularização de coroide. A melhor correção visual e o exame de tomografia de coerência óptica com análise da espessura macular foram registrados em cada visita. As injeções de ranibizumab e bevacizumab intravítrea foram feitas até a resolução do líquido sub-retiniano pela tomografia de coerência óptica e clinicamente. Todos os pacientes tinham seguimento de 6 meses do diagnóstico a 2 anos, com média de 16 meses. RESULTADOS: Onze olhos de 10 pacientes incluídos receberam uma média de 7 ± 3 injeções intravítreas de ranibizumab e bevacizumab, sendo que 7 apresentaram redução do espessamento macular pelo tomografia de coerência óptica. A mácula teve o espessamento reduzido entre 72 ± 115 µm, 6 olhos tiveram melhora de 1 ou mais linhas de visão, um olho teve acentuada diminuição da visão e um outro não teve alteração. A média do resultado do tratamento em logMAR era -0,04 ± 0,46 correlacionando um ganho de visão na tabela de Snellen entre 0,2 ± 4,4 linhas de visão. CONCLUSÕES: Estes resultados sugerem que o uso do ranibizumab e bevacizumab intravítrea para neovascularização de coroide da degeneração macular relacionada à idade em extensa atrofia geográfica pré-existente é eficaz. Há, entretanto dificuldades na avaliação da acuidade visual destes pacientes em virtude da extensa atrofia geográfica que apresentavam e sobre esta ainda a neovascularização de coroide, se comparados a casos em que a neovascularização de coroide não ocorre em atrofia geográfica pré-existente.

Central Serous Retinopathy in Old Age

Central serous retinopathy is a serous detachment of sensory retina in macular area resulting from retinal pigment epithelial defect. It usually affects adult between 25 and 50 years of age. Central serous retinopathy which occured in 50 years of age or older can be readily mistaken for senile macular degeneration with subretinal neovascularization, Two diseases must be differentiated because of different progress and treatment. Thirteen patients were 50 years of age or older among 172 patients with central serous retinopathy, There were 3 eyes with retinal pigment epithelial atrophy but there were no eyes with soft drusen, geographic atrophy and subretinal neovascular membrane. Subretinal neovascular membrane was not seen during follow up period also. Seven eyes received conservative treatment and 6 eyes received argon laser photocoagulation. Visual acuity of all patients improved to more than 20/50 after treatment and visual prognosis is not different with that of young adult.