Switch to aflibercept in the treatment of neovascular age-related macular degeneration: 30-month results / Mudança de tratamento para o aflibercepte no tratamento da Degeneração Macular neovascular Relacionada à Idade: resultados de 30 meses

ABSTRACT Purpose: This study was conducted to evaluate visual function and changes in the central macular thickness of patients with unresponsive neovascular age-related macular degeneration who were switched from ranibizumab (Lucentis®) to aflibercept (Eylea®) treatment at 30 months. Methods: This retrospective study examined patients with neovascular age-related macular degeneration who were switched to aflibercept after ≥6 previous intravitreal ranibizumab injections at 4- to 8-week intervals. All patients were switched to intravitreal aflibercept (2.0 mg) and analyzed after 3 consecutive injections followed by a prore nata dosing regimen and after 30 months of treatment. Best corrected visual acuity, biomicroscopic examination, intraocular pressure, fundus examination, and central macular thickness were recorded at the start of treatment, before the transition to intravitreal aflibercept treatment, and at 6, 12, 18, 24, and 30 months of intravitreal aflibercept treatment. Results: A total of 33 eyes met the inclusion criteria. The median age of the patients was 73.57 ± 7.98 years, and 21 (61.8%) patients were males and 12 (35.3%) were females. Before the transition, the patients received a mean of 16.8 ± 8.8 ranibizumab injections (range 6-38).After the transition to intravitreal aflibercept treatment, the mean number of aflibercept injections was 9.09 ± 3.94. No significant differences were observed in best corrected visual acuity after the aflibercept switch in any of the months. The central macular thickness was significantly decreased at 6, 12, 18, and 30 months (p=0.01, p=0.03, p=0.05, p=0.05, p<0.001, respectively). Conclusion: Patients with neovascular age-related macular degeneration who were switched to intravitreal aflibercept treatment due to unresponsiveness to intravitreal ranibizumab exhibited a significant anatomic improvement in the retina, and although this state persisted, there was no significant functional gain.(AU)

RESUMO Objetivo: Avaliar, depois de 30 meses, a função visual e as alterações na espessura macular central de pacientes com degeneração macular relacionada à idade sem resposta terapêutica ao ranibizumabe (Lucentis®) que mudaram seu tratamento para o aflibercepte (Eylea®). Métodos: Realizou-se um estudo retrospectivo de pacientes com degeneração macular neovascular relacionada à idade que mudaram o tratamento para o aflibercepte após 6 ou mais injeções intravítreas de ranibizumabe a intervalos de 4-8 semanas. Todos os pacientes mudaram para o aflibercepte intravítreo (2,0 mg) e depois de 3 injeções consecutivas, seguidas de um regime de dosagem pro re nata, foram avaliados após 30 meses de tratamento. A melhor acuidade visual corrigida, o exame biomicroscópico, a pressão intraocular, a fundoscopia e a espessura macular central foram registrados no início do tratamento, antes da transição para o tratamento com aflibercepte intravítreo e aos 6, 12, 18, 24 e 30 meses de tratamento com o aflibercepte intravítreo. Resultados: Satisfizeram aos critérios de inclusão 33 olhos. A mediana da idade dos pacientes foi de 73,57 ± 7,98 anos. Dos pacientes, 21 (61,8%) eram homens e 12 (35,3%) eram mulheres. Antes da transição para o tratamento com o aflibercepte intravítreo, os pacientes receberam em média 16,8 ± 8,8 injeções de ranibizumabe (faixa 6-38).Depois da transição, o número médio de injeções de aflibercepte foi de 9,09 ± 3,94. Não houve diferenças significativas na melhor acuidade visual corrigida depois da mudança para o aflibercepte em qualquer das avaliações. Houve diminuição significativa da espessura macular central aos 6, 12, 18 e 30 meses (respectivamente, p=0,01, p=0,03, p=0,05, p=0,05 e p<0,001). Conclusão: Pacientes com degeneração macular neovascular relacionada à idade que mudaram seu tratamento para o aflibercepte intravítreo devido à falta de resposta ao ranibizumabe intravítreo, tiveram melhora anatômica significativa da retina; mas embora esse estado tenha persistido, não foi observado nenhum ganho funcional significativo.(AU)

Association between disorganization of the retinal inner layers and capillary nonperfusion area in patients with retinal vein occlusion / Associação entre a desorganização das camadas internas da retina e areas sem perfusão capilar em pacientes com oclusão de veia retiniana

ABSTRACT Purpose: To determine the correlation between the extent of disorganization of the retinal inner layers (a parameter of spectral domain optical coherence tomography) and optical coherence tomography angiography parameters in eyes with center-involved macular edema associated with retinal vein occlusion. Methods: This retrospective observational study included 34 eyes of 34 patients with newly diagnosed macular edema associated with retinal vein occlusion and evidence of center-involved macular edema. Optical coherence tomography angiography and spectral domain optical coherence tomography were evaluated after resolution of the macular edema. Disorganization of the retinal inner layers was determined via spectral domain optical coherence tomography and optical coherence tomography angiography parameters, including foveal avascular zone area in the superficial capillary plexus and capillary nonperfusion areas, foveal avascular zone area in full retinal vasculature, foveal avascular zone perimeter, acircularity index of the foveal avascular zone, and foveal density. Results: The mean disorganization of the retinal inner layers extent was 512.72 ± 238.47 microns, and the mean capillary nonperfusion area was 4.98 ± 2.85 mm2. There was a positive correlation between the extent of disorganization of the retinal inner layers and capillary nonperfusion area (p<0.001, r=0.901). Greater extent of disorganization of the retinal inner layers and the capillary nonperfusion area was correlated with wider foveal avascular zone area (p=0.014 and p=0.036, respectively) in the superficial capillary plexus and decreased foveal density (vessel density in 300 microns around the foveal avascular zone) (p=0.031 and p=0.022, respectively). These parameters were also correlated with decreased vessel density in both the superficial capillary plexus and deep capillary plexus in the parafoveal and peri­foveal regions (p<0.05 for all). Conclusions: Disorganization of the retinal inner layers appears to be a correlated biomarker of capillary ischemia in retinal vein occlusion. The extent of disorganization of the retinal inner layers was strongly correlated with the capillary nonperfusion area. This may support the notion that the extent of disorganization of the retinal inner layers can be used as an easily obtainable and crucial surrogate marker of capillary ischemia.

RESUMO Objetivo: Determinar a correlação entre a ex­tensão da desorganização das camadas internas da retina, que constitui um parâmetro da tomografia de coerência óptica de domínio espectral, e os parâmetros da angiografia por tomografia de coerência óptica em olhos com edema macular com envolvimento central associado à oclusão da veia retiniana. Métodos: Este estudo retrospectivo observacional incluiu 34 olhos de 34 pacientes com edema macular recém-diag­nosticado associado à oclusão da veia retiniana e com evidência de edema macular com envolvimento central. Após a resolução do edema macular, foram avaliadas a tomografia de coerência óptica de domínio espectral e a angiografia por tomografia de coerência óptica. A desorganização das camadas internas da retina foi determinada através de parâmetros da tomografia de coerência óptica de domínio espectral e da angiografia por tomografia de coerência óptica, incluindo a área da zona avascular foveal no plexo capilar superficial e nas regiões sem perfusão capilar, a área da zona avascular foveal na vascularização total da retina, o perímetro da zona avascular foveal, o índice de não circularidade da zona avascular foveal e a densidade foveal. Resultados: A extensão média da desorganização das camadas internas da retina foi de 512,72 ± 238,47 mm e a área média da região sem perfusão capilar foi de 4,98 ± 2,85 mm2. Houve uma correlação positiva entre a extensão da desorganização das camadas internas da retina e a área da região sem perfusão capilar (p<0,001, r=0,901). Maior extensão da desorganização das camadas internas da retina e da região sem perfusão capilar correlacionaram-se a uma área maior da zona avascular foveal (respectivamente, p=0,014 e p=0,036) no plexo capilar superficial e a uma menor densidade foveal (a densidade vascular nos 300 μm à volta da zona avascular foveal; respectivamente, p=0,031 e p=0,022), e também se correlacionaram a uma menor densidade vascular tanto no plexo capilar superficial como no profundo, nas regiões parafoveal e perifoveal (p<0,05 em todas as correlações). Conclusão: A desorganização das camadas internas da retina parece ser um biomarcador correlacionado com a isquemia capilar na oclusão da veia retiniana. O fato de que a extensão dessa desorganização se correlacionou fortemente com a área sem perfusão capilar sugere o uso da extensão da desorganização das camadas internas da retina como um marcador substituto de isquemia capilar, sendo este um marcador importante e facilmente obtido.

Damage of blue-light exposure to retinal morphology and function in mice / 中华实验眼科杂志

Objective@#To study the damage effects of blue-light exposure on retinal morphology and function in mouse.@*Methods@#Twenty 8-week-old clean C57BL/6J mice were randomly divided into blue-light exposure group and normal control group by coin tossing method.The mice in the blue-light exposure group was exposed to 10 000 lx blue light for 5 days after dark adaptation for 24 hours, and the mice in the normal control group was kept under the normal light intensity for 5 days at 12-hour light/12-hour darkness cycles.The retinal thickness was detected by optical coherence tomography (OCT), and retinal function was evaluated by electroretinogram (ERG). The mice was sacrificed and the frozen section and flat mount of eyeball wall was created at 24 hours after irradiation.The expressions of rhodopsin (Rho), zonula occludens-1 (ZO-1) and β-catenin in the retinas were detected by immunofluorescent staining.The use and care of the experimental animals adhered to ARVO Statement by American Society of Visual and Ophthalmological Sciences (No.IACUC-1803029).@*Results@#The thickness of the retinal outer nuclear layer at 200, 400, 600, 800 and 1 000 μm from the superior and inferior to optic nerves were thinned in the mice of the blue-light exposure group compared with those of the normal control group, showing significant differences between the two groups (all at P<0.05). The b-wave amplitude of the scotopic and photopic ERG was (305.50±41.52)μV and (119.50±6.67)μV in the blue-light exposure group, respectively, which was significantly reduced in comparison with (415.50±28.77)μV and (139.75±8.26)μV of the normal control group (both at P<0.05). Immunofluorescent staining showed that the retinal pigment epithelial (RPE) cells of the mice exhibited hexagonal shape with regular arrangement, retinal morphology was regular, and the expressions of Rho, ZO-1 and β-catenin proteins showed stronger fluorescence in the retinas of normal control group.However, structural disorder, diminishing fluorescence intensity of Rho, ZO-1 and β-catenin were found in the blue-light exposure group.The morphology of the retina was disordered while the cell structure was destroyed.@*Conclusions@#Blue-light irradiation results in morphological and functional damages of retina.

Damage of blue-light exposure to retinal morphology and function in mice / 中华实验眼科杂志

Objective To study the damage effects of blue-light exposure on retinal morphology and function in mouse.Methods Twenty 8-week-old clean C57BL/6J mice were randomly divided into blue-light exposure group and normal control group by coin tossing method.The mice in the blue-light exposure group was exposed to 10 000 lx blue light for 5 days after dark adaptation for 24 hours,and the mice in the normal control group was kept under the normal light intensity for 5 days at 12-hour light/12-hour darkness cycles.The retinal thickness was detected by optical coherence tomography (OCT),and retinal function was evaluated by electroretinogram (ERG).The mice was sacrificed and the frozen section and flat mount of eyeball wall was created at 24 hours after irradiation.The expressions of rhodopsin (Rho),zonula occludens-1 (ZO-1) and β-catenin in the retinas were detected by immunofluorescent staining.The use and care of the experimental animals adhered to ARVO Statement by American Society of Visual and Ophthalmological Sciences (No.IACUC-1803029).Results The thickness of the retinal outer nuclear layer at 200,400,600,800 and 1 000 μm from the superior and inferior to optic nerves were thinned in the mice of the blue-light exposure group compared with those of the normal control group,showing significant differences between the two groups (all at P＜0.05).The b-wave amplitude of the scotopic and photopic ERG was (305.50±41.52) μV and (119.50±6.67)μV in the blue-light exposure group,respectively,which was significantly reduced in comparison with (415.50±28.77) μV and (139.75±8.26) μV of the normal control group (both at P＜ 0.05).Immunofluorescent staining showed that the retinal pigment epithelial (RPE) cells of the mice exhibited hexagonal shape with regular arrangement,retinal morphology was regular,and the expressions of Rho,ZO-1 and β-catenin proteins showed stronger fluorescence in the retinas of normal control group.However,structural disorder,diminishing fluorescence intensity of Rho,ZO-1 and β-catenin were found in the blue-light exposure group.The morphology of the retina was disordered while the cell structure was destroyed.Conclusions Blue-light irradiation results in morphological and functional damages of retina.

Wide-field angiography for diagnosis and follow-up of Eales disease: a case series / Angiografia de amplo campo para diagnóstico e monitoramento da doença de Eales: série de casos

ABSTRACT Wide-field angiography enables assessing peripheral areas with better quality and gives greater deep focus, which improves the image periphery. Some studies have proposed the usefulness of these angiographic systems in inflammatory diseases of the retina. However, few studies have evaluated this technique in Eales disease. We present a case series in which 5 eyes of 3 patients with Eales disease were evaluated by using retinal fluorescein angiography with 30º, 50º, and 150º lenses in a laser-scanning ophthalmoscope. These cases highlight the usefulness of wide-field fluorescein angiography in the diagnosis and follow-up of peripheral ischemic retinal areas in Eales disease, which enables better follow-up than possible with conventional fluorescein angiography images.

RESUMO A angiografia de campo amplo permite avaliar áreas periféricas com melhor qualidade e proporciona maior foco profundo, melhorando a imagem da periferia. Alguns estudos têm proposto a utilidade desses sistemas angiográficos nas doenças inflamatórias da retina. No entanto, poucos estudos avaliaram esta técnica na doença de Eales. Apresentamos uma série de casos em que 5 olhos de 3 pacientes com doença de Eales foram avaliados usando angiografia de fluoresceína da retina com lentes de 30º, 50º e 150º em um oftalmoscópio de varredura a laser. Esses casos destacam a utilidade da angiografia com fluoresceína de campo amplo no diagnóstico e no acompanhamento das áreas isquêmicas periféricas da retina na doença de Eales, permitindo um melhor acompanhamento do o possível com imagens por angiofluoresceinografia convencional.

Frequência de achados oftalmológicos de segmento posterior em pacientes com doença inflamatória intestinal / Frequency of ophthalmological posterior segment findings in patients with inflammatory bowel disease

ABSTRACT BACKGROUND: Inflammatory bowel disease is a systemic inflammatory disease classified as Crohn disease or ulcerative colitis. It could present extra intestinal findings, such as fever, weight loss, arthralgia, mucocutaneous lesions, hepatic, renal and ophthalmological involvement. Among ophthalmological findings, posterior segment findings are present in less than 1% of patients with inflammatory bowel disease, however, these findings could bring definitive visual impairment. OBJECTIVE: Our study objective was to evaluate ocular posterior segment findings is patients with inflammatory bowel disease, through retinal mapping, color fundus retinography, optical coherence tomography (OCT) and OCT angiography, and compare our results to literature. METHODS: We evaluated eighty patients with inflammatory bowel disease through complete ophthalmological examination and posterior segment assessment. Color fundus retinography, OCT and OCT angiography was performed with Topcon Triton (Topcon ® , Tokyo, Japan). Macula and posterior pole were evaluated with binocular indirect ophthalmoscopy and fundus biomicroscopy. RESULTS: Participants mean age was 44.16 years (18.08-68.58), 28 (35%) male patients and 52 (65%) female patients. Thirty-five (44%) with diagnosis of Crohn disease, 41 (52%) patients with diagnosis of ulcerative colitis and 3 (4%) had non-conclusive Crohn disease or ulcerative colitis classification. We found abnormal exams in 21 (26.25%) patients. CONCLUSION: Our study found similar prevalence of ophthalmological posterior segment commitment compared to previous literature prevalence. The findings were predominantly unrelated to inflammatory bowel disease, rather than primarily related to it. The most prevalent, and non-previous reported, finding was increased arteriolar tortuosity, probably occurs due to systemic vascular impairment in inflammatory bowel disease.

RESUMO CONTEXTO: As doenças inflamatórias intestinais são doenças inflamatórias sistêmicas que podem ser divididas em doença de Crohn ou retocolite ulcerativa. Além do quadro intestinal, elas podem apresentar sintomas extra intestinais como febre, perda de peso, artralgia, lesões mucocutâneas, acometimento hepatobiliar, acometimento renal e oftalmológico. Entre os achados oftalmológicos descritos, alterações de segmentos posterior são encontrados em menos de 1% dos pacientes com doença inflamatória intestinal, porém, tais achados podem levar à baixa acuidade visual definitiva. OBJETIVO: O objetivo do nosso trabalho foi avaliar alterações em segmento posterior através de retinografia colorida, mapeamento de retina, tomografia de coerência óptica e OCT angiography e comparar nossos resultados com o da literatura. MÉTODOS: Foram avaliados 80 pacientes com doença inflamatória intestinal. Todos os pacientes foram submetidos a exame oftalmológico completo e a avaliação do segmento posterior. Foi realizada tomografia de coerência óptica em aparelho Triton (Topcon, Tokyo, Japan), retinografia colorida e OCT angiography. Mácula e polo posterior foram avaliados através de oftalmoscopia binocular indireta e biomicroscopia de fundo. RESULTADOS: Entre os participantes, a média de idade foi de 44,16 anos (18,08-68,58), 28 (35%) participantes do sexo masculino e 52 (65%) do sexo feminino. Trinta e cinco (44%) pacientes com diagnóstico de doença de Crohn, 41 (52%) pacientes com diagnóstico de retocolite ulcerativa e 3 (4%) pacientes em que não era possível classificar como doença de Crohn ou retocolite ulcerativa. Entre as avaliações de polo posterior, foram encontrados achados em exame de 21 pacientes, o que corresponde a 26,25% dos casos. CONCLUSÃO: Nosso estudo encontrou resultados de prevalência de achados em exame de segmento posterior semelhante aos estudos prévios da literatura. Os achados foram de forma predominante não primariamente relacionados à doença inflamatória intestinal. O achado mais prevalente, e não previamente reportado, foi aumento de tortuosidade arteriolar, que provavelmente ocorre por envolvimento vascular sistêmico nas doenças inflamatórias intestinais.

Maculopatia viteliforme polimorfa exudativa aguda: um relato de caso / Acute exsudative polymorphous vitelliform maculopathy: a case report

Resumo A maculopatia viteliforme polimorfa exsudativa aguda é um distúrbio retiniano extremamente raro, que tem sido considerado como uma forma de retinopatia paraneoplásica, encontrada em pacientes com um tumor primário subjacente. Os sintomas de maculopatia viteliforme polimorfa exsudativa aguda incluem dor de cabeça precedente seguida de perda aguda da visão. O fundo de olho de um paciente com essa condição demonstra geralmente depósitos bilaterais, branco-amarelados na região macular. O relato de uma doença rara e que tem uma forte associação com neoplasia oculta é de extrema relevância, pois ajuda a conhecer melhor a sua historia natural, possíveis complicações e prognóstico.

Abstract Acute exudative polymorphous vitelliform maculopathy is an extremely rare retinal disorder, that has been considered as a form of paraneoplasic retinopathy, found in patients with a underlying primary tumor. Symptoms of acute exudative polymorphous vitelliform maculopathy include preceding headache followed by acute onset of vision loss. The fundus of a patient with this condition typically demonstrates bilateral, subretinal white-yellow deposits in the macular region. The report of a rare disease which has a strong association with underlying neoplasia is extremely relevant whereas it helps better comprehend its genuine history, possible complicacy and prognosis.

Optical coherence tomography and congenital retinoschisis: three case reports / Tomografia de coerência óptica e retinosquise congênita: relato de três casos

Abstract Congenital retinoschisis is an X-linked recessive inherited disease. It causes the splitting of the retina's neurosensory layers from the remaining of the sensory retina, presenting itself as a "stellate" or "bicycle-wheel" maculopathy, vitreous hemorrhage and retinal detachment. We report three cases of congenital retinoschisis, two of them brothers. optical coherence tomography was used when evaluating the cases. It was impossible to differentiate retinoschisis from retinal detachment in one of the cases through optical coherence tomography due to lack of patient collaboration. We then performed laser photocoagulation to mark and follow-up the affected area.

Resumo A retinosquise congênita é uma doença autossômica recessiva ligada ao X. Resulta em separação da camada de fibras nervosas do restante da retina sensorial, e manifesta-se como maculopatia estriada, hemorragias vítreas e descolamento de retina. Relatamos três casos de retinosquise congênita, sendo dois deles irmãos. Utilizou-se a tomografia de coerência óptica na avaliação dos casos. Em um, não foi possível efetuar o diagnóstico diferencial com descolamento de retina através da tomografia de coerência óptica, devido a não cooperação no exame, optando-se pela realização de fotocoagulação com laser para demarcação e seguimento da área.

Comparison of retinal histomorphology following laser photocoagulation using 577 nm subliminal micropulse laser versus 577 nm laser in pigmented rabbits / 中华实验眼科杂志

Background Studies showed that 577 nm subliminal micropulse photocoagulation for retinal diseases is more effective and much safer than 577 nm laser,but its mechanism and sensitive target cells are still unelucidated.Objective This study was to compare the histomorphology changes of rabbit retinas following 577 nm subliminal micropulse excitation and 577 nm laser for retinal photocoagulation and offer a conference for the clinical application of 577 nm subliminal micropulse excitation.Methods Twenty-six Chinese pigment rabbits were randomly divided into normal control group (2 rabbits),577 nm laser photocoagulation group (6 rabbits) and subliminal micropulse photocoagulation group (18 rabbits),in which the rabbits from subliminal micropulse photocoagulation group were subgrouped into 9％,12％ and 15％ subthreshold photocoagulation groups according to the different workload rates,and retinal photocoagulation was performed based on grouping.No treatment was carried out in the normal control group.Fundus camera and OCT were obtained after photocoagulation,and the rabbits were sacrificed to prepare the specimen of eyeball wall.Hematoxylin and eosin staining was employed to examine the histopathological change of choroid and retina under the light microscope.Results The retinal morphology was normal on the fundus color photography and OCT in the normal control group.Obscure of retinal structure and slight edema of retinal neuroepithelial layer with obscure of retinal pigment epithelium (RPE) was found respectively in the 9％ and 12％ subthreshold photocoagulation group,and serious edema of retinal neuroepithelial layer with local RPE elevation was visible in the 15％ subthreshold photocoagulation group.The laser spot was invisible in various subliminal micro pulse groups.However,retinal photocoagulation spots,multifocal elevation of retinal layer and serious detachment of retinal neuroepithelium were found in the 577 nm laser group.Retinal histopathological examination revealed that the photoreceptors,bipolar cells and retinal ganglion cell (RGC) layers were normal,while choroidal vessel deformation and bleeding were visible in the 9％ and 12％ subthreshold photocoagulation groups,and only photoreceptor membrane swelling was seen in the 15％ subthreshold photocoagulation group.However,retinal structure abnormality was displayed in 577 nm laser group,including the structural disorders of inner and outer nuclear layers and RGC layer as well as thinning of RPE layer.Conclusions 577 nm nicropulse laser under threshold is sensitive for RPE and choroid rather than retina neurepithelium,which can play a treating role and also does not damage retina seriously.However,577 nm laser photocoagulation results in retinal structure damage.

The protactive effects and mechanisms of cx3cr1 antibody on retinal neuron in rats with ischemia reperfusion injury by intravitreal injection / 中华实验眼科杂志

Background Study confirmed that the active microglia may injure retinal ganglion cells (RGCs) in retinal ischemia reperfusion injury (IRI), and increased cx3cr1 expression is an important factor in microglial activation,and thus blocking the expression of cx3cr1 can inhibit microglial activation, which may be useful in neuronal protection.Objective This study was to analyze the protective effects of cx3cr1 antibody on retinal neuron in rat eyes with IRI.Methods Ninety SD rats were divided into 4 groups according to random number table.IRI models were established by perfusing normal saline solution into the anterior chamber.The cx3cr1 antibody of 1 μl (0.2 μg/μl) was intravitreally injected in the right eyes in the normal rats or model rats as the only cx3cr1 antibody injected group and the model cx3cr1 antibody injected group,respectively,and no any drug was injected in the rats of the normal control group and model control group.Retinal sections were prepared 48 hours after modeling, and apoptosis of retinal neutron was observed under the transmission electron microscope;the morphology of retinas was exmined and the number of survival RGCs was calculated by histopathologic method.The expression of CD68 in activated retinal microglial cells was detected by immunochemistry, and the relative expression levels of cx3cr1 mRNA,tumor necrosis factor-α (TNF-ct) mRNA and interleukin-1 β (IL-1 β) mRNA in the retinas were assayed by real time quantitative PCR.Results The cell nucleus of RGCs showed the round and ellipse in shape and there were abundant organelles in the cells.The mophology of photoreceptors was normal with abundant mitochondrions.Irregular cell shape, disrupture of outer segment membranous disc, proliferative microglial cells in RGC layer were seen in the model group.However,these findings were mild in the model cx3crl antibody group.The mean number of survival RGCs was (38.100 ± 3.929), (37.200 ± 5.266), (26.700 ± 2.584) and (31.700 ± 2.946)/field in the normal control group,only cx3cr1 antibody injected group, model control group and model cx3cr1 antibody injected group,showing significant differences between the model group and the normal control group, only cx3cr1 antibody injected group or model cx3cr1 antibody injected group (t =7.492,6.125,-4.607, all at P＜0.01).The expression levels (absorbance) of CD68 in rat retinas were significantly higher in the model group than those in the normal control group, only cx3cr1 antibody injected group and model cx3cr1 antibody injected group (t =-3.397 ,P =0.008;t =-6.207 ,P =0.000;t =3.494, P =0.007).The relative expression levels of cx3cr1 mRNA, TNF-α mRNA and IL-1 β mRNA in rat retinas were raised in the model group compared with the only cx3er1 antibody injected group and model cx3cr1 antibody injected group (all at P＜0.01).No significant differences were observed in these indicators between the normal control group and the only cx3crl antibody injected group (all at P＜0.05).Conclusions Intravitreal injection of cx3cr1 antibody to neutralize cx3cr1 levels in retinas can effectively inhibit the activation of retinal microglia,decrease the release of inflammatory factors, reduce the apoptosis of RGCs and thereby protect the retinal neutrons against IRI in SD rats.Intravitreal injection of cx3cr1 is safe and feasible.

Oclusão da artéria central da retina em paciente com poliangeíte microscópica / Central retinal artery occlusion in patient with microscopic polyangiitis

RESUMO A poliangeíte microscópica é uma vasculite necrotizante sistêmica que acomete arteríolas, capilares e vênulas, mas também pode atingir pequenas e médias artérias. É considerada uma doença rara, idiopática e autoimune. Diversas anormalidades oculares e sistêmicas estão associadas às oclusões arteriais retinianas. Dentre as doenças vasculares do colágeno, a literatura cita como possíveis causas de obstrução das artérias retinianas o lúpus eritematoso sistêmico, a poliarterite nodosa, a arterite de células gigantes, a granulomatose de Wegener e a granulomatose linfóide de Liebow. Até o presente momento, não se encontrou na literatura relatos da associação de casos de oclusão arterial retinana associados à PAM. Os autores relatam o caso de um paciente com poliangeíte microscópica que apresentou comprometimento renal importante e oclusão da artéria central da retina unilateral. Atenta-se para a inclusão de pesquisa da PAM, através do p-ANCA, na avaliação de possível origem sistêmica em pacientes acometidos por oclusão arterial retiniana.

ABSTRACT The microscopic polyangiitis is a systemic necrotizing vasculitis that affects arterioles, capillaries and venules, but can also reach small and medium-sized arteries. It is considered a rare disease, idiopathic in nature but clearly autoimmune. Several ocular and systemic abnormalities are associated with retinal arterial occlusions. Among the collagen vascular diseases, the literature cited as possible causes of retinal artery obstruction lupus erythematosus, polyarteritis nodosa, giant cell arteritis, Wegener’s granulomatosis and lymphoid Liebow. Until now, there were no reports in the literature of the association of cases of arterial occlusion retinana associated with PAM. The authors report a case of a 53 years old patient diagnosed with microscopic polyangiitis who presented with important renal artery occlusion and associated unilateral central retinal artery occlusion. An extended systemic evaluation of patients presenting with central retinal artery occlusion should include research of PAM through analysis op p-ANCA.

Methodology of trans-corneally subretinal injection in mice / 中华实验眼科杂志

Background Trans-corneally subretinal injection in rodent model is a useful method for genetic therapy,stem cell transplantation and the study on the ophthalmic research.Standarized operation process is critical for the successful treatment.However,there is no literature to report the detailed procedure and the influence of this technique on morphology and function of retina.Objective This sudy was to introduce a method of trans-corneally subretinal injection and evaluate its influence on the morphology and function of retina.Methods Trans-corneallly subretinal injection was performed on the left eyes of 2-month-old SPF C57BL/6J mice after dilation of pupils.A 301/2G disposable needle was used to puncture the cornea within the pupil area near limbus and avoid touching the lens and irises under eye surgery microscope.Then,a 33G blunt needle was used to insert into the vitreous and toward subretinal space via corneal puncture.Normal saline with 0.1％ fluorescein sodium of 1 μl was slowly injected into the space,and 2.5％ hydroxypropyl methylcellulose was dropped on ocular surface for the observation of the fundus clearly.According to the percentage of the retina filled with subretinally injected solution,the experimental eyes were divided into 80％-100％ area group,50％-70％ area group after injection,and the mice in the pseudo-injected group,in which injection procedure stopped just before the solution was pushed in to the subretinal space did not inject any solution after punctured.The right uninjected eyes of the mice served as normal control group.Four eyes were selected for each group.The structural changes were evaluated by optical coherance tomograpby (OCT) 1 day,2 days,3 days and 5 weeks after injection,and retinal function was assessed by the recored of electroretinography (ERG) 5 weeks after injection.The retinal sepcimens were prepared to examin the morphological changes by hematoxylin and esosin staning.The use of care followd the Regulations for the Administration of Affair Concerning Experimental Animals of Zhejiang Province.Results About 70％ of the injected eyes showed that retinal blebs filled with injected green fluorescein solution occupied 50％ or more retinal area with minimal damages.The focal detachment between neurosensory retinal layer and retinal pigment epithelium (RPE) was exhibited 1 day postinjection,and almost all the retinas retached 2 days after injection.In the fifth week after injection,the amplitudes of ERG b wave were (386.25±37.88),(357.50±41.03),(324.25±53.45) and (410.50±14.88) μV in the sham operation group,50％-70％ area group,80％-100％ area group and normal control group,respectively,showing a significant difference among the 4 groups (F=3.574,P=0.047),and the amplitudes of b wave in the normal control group were higher than those in the 80％-100％ area group (all at P ＜ 0.05).The detachment between retinal neuroepithelium layer and RPE layer,cell proliferation and transposition in the outer nuclear layer were dispalyed under the light microscope in the sham operation group,50％-70％ area group and 80％-100％ area group,and the disordered outer segment of photoreceptors at the injecting area was seen in the 50％-70％ area and 80％-100％ area groups at five weeks after injection.However,retinal sructure and morphology were normal at the non-injection area.Conclusions Trans-corneally subretinal injection is an effective and safe way for subretinal injection.

Study on human adipose mesenchymal stem cells differentiating into retinal pigment epithelial-like cells and its in vivo application / 中华实验眼科杂志

Background Stem cell transplantation represents a promising treatment option for patients suffering from degenerative disorders.Accumulating evidences indicate that mesenchymal stem cells (MSCs) are able to differentiate into retinal pigment epithelial (RPE)-like cells.However,MSCs are difficult to obtain.Human adipose mesenchymal stem cells (ADSCs) are proved to have similar properties to MSCs,but relevant study is less.Objective This study was to assess the feasibility of human ADSCs differentiating into RPE-like cells and the safety of its application in vivo.Methods The third generation of human ADSCs were incubated into 6-well plate,and 100 ng/ml epithelial growth factor,50 μ mol/L taurine and 5×10-7 mol/L retinoic acid were added into the medium 12 hours after cultured to induce the cells,and conventional cultured cells were used as the control group.Induced cells were traced with PKH26,and Pan-cytoke ratin (Pan-CK) monoclonal antibody was used to identify the cells under the fluorescence microscope.Induced RPE-like cell suspension of 1 μl was intravetreally injected in the right eyes of 6 BALB/c mice,and equal volume of PBS was used in the same way in another 6 mice.The animals were sacrificed 1 month after injection,and the retinal morphology was examined by histopathology under the optical microscope.The ultrastructure of retinal ganglion cells (RGCs) was examined by the transmission electron microscope.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results Cultured human ADSCs grew well with the slender polygone shape.Cell membranes showed the red fluorescence for PKH26 after induced.In addition,Pan-CK was expressed in the cell membranes with the red fluorescence in the induced cells,but the response was absent in the control cells.One month after intravitreal injection,induced cells located on the retinal surface,and the retinal morphology was clear under the optical microscope.No abnormality in RGCs was seen under the transmission electron microscope.Conclusions Human ADSCs can differentiate into RPE-like cells after induction.PKH26 can mark induced cells well.There is no adverse effect of induced cells on retina after intravitreal injection in a short-term duration in mice.

Retinal toxicity of repeated intravitreal injection with bevacizumab in diabetic rats / 中华眼底病杂志

Objective To observe the retinal toxicity of repeated intravitreal injection with bevacizumab(Avastin)in diabetic rats.Methods Forty male Sprague Dawley(SD)rats were randomly divided into normal group(Group A,10 rats)and diabetes mellitus group(30 rats).The rats in diabetes mellitus group were induced with streptozotocin injection for diabetic retinopathy model.And then randomly divided into diabetic retinopathy(DR)group(Group B,10 rats),the rats were not intervened;the left eyes of the other 20 rats were intravitreal injected with bevaeizumab 3 μ1(25 mg/m1)for 3 times as experimental group(Group C);the right eyes of the 20 rats were not intervened as experimental control group(Group D),20 days after last intravitreal injection,retinal function was measured by Flicker Electroretinogram (F-ERG);retinal vascular pattern was determined by fluorescence microscopy of ethidium bromide(EB)stained retinal flat mounts;retinal morphological changes were determined by light microscope on hematoxylin-eosin (HE) stained sections;Thy-1 and VEGF expression was measured by immunohistochemistry staining.Results F-ERG showed that-the differences of a-and b-waves-the b-wave amplitude and the Ops-wave amplitude in the implicit time between group A,B,C and D were significant (F=33.165,36.162,19.955,23.243;P=0.000);the differences of a-wave amplitude between group A,B,C and D was not significant(F=0.097,P=0v961).Retinal blood vessel pattern was normalin Group A;retinal vascular vessels were tortuous and irregularly expanded in Group B:retinal vascular vessels of Group C were regular and thinner than Group A;microaneurysm were showed in Group D.Light microscope displayed that the layers of the rat retina of Group A were regular,the retinal architectures of Group B were irregular,the retinal layers were regular in Group C,the retinal layers were irregular in Group D.Immunohistochemistry staining discovered that Thy-1 and VEGF were mainly expressed in ganglion cell layer(GCL).Conclusion Repeated intravitreal injection of bevacizumab iS toxic tO retina of diabetes mellitus rats.

Avaliação da espessura da camada de fibras nervosas da retina e mácula em pacientes com ambliopia / Thickness of the retinal nerve fiber layer, macular thickness, in patients with amblyopia

OBJETIVO: Avaliar a espessura da camada de fibras nervosas da retina em olhos amblíopes e comparar com olhos normais e certificar se há correlação com a redução da acuidade visual. Além disso, este estudo se propõe avaliar a eficácia e eficiência em uma série de casos do protótipo de um equipamento nacional de magnificação para leitura. MÉTODOS: Participaram deste estudo 30 pacientes na faixa etária entre 9 e 80 anos (17 do sexo masculino). Foi desenvolvido um aparelho portátil, patenteado pela Unifesp (PI#020050145260), com um sistema de captura de imagens acoplado a um monitor de 5,6 polegadas proporcionando um aumento de 15 x. Foram analisadas a eficácia da acuidade visual e a eficiência de leitura após a utilização do protótipo proposto. RESULTADOS: Seis pacientes (20 por cento) apresentaram AV 8M, 12 pacientes (40 por cento) apresentaram AV 6M, 7 pacientes (23,3 por cento) apresentaram 5 M, 5 pacientes (16,7 por cento) apresentaram 4M. A média de acuidade visual antes da utilização do SLP medida pela tabela LHNV-1 logMAR foi de 5,75M e após a utilização 100 por cento dos pacientes atingiram a eficácia de AV J1. CONCLUSÃO: O protótipo do SLP mostrou-se um recurso alternativo no processo de inclusão social das pessoas com baixa visão com diferentes níveis de resíduo visual. Também pode proporcionar incentivo psicológico, permitir conforto, mobilidade e independência àqueles que necessitam de uma leitura mais prolongada e maior distância de trabalho.

OBJECTIVE: To compare the thickness of the retinal nerve fiber layer (RNFL)and the macular thickness of the amblyopic eye with those of the non-amblyopic eye in patients with unilateral amblyopia using optical coherence tomography (OCT). METHODS: OCT was performed for13 patients with unilateral amblyopia who had no neurologic disease. Nine male andfour female patients, whose ages ranged from 23 to 63 years, were enrolled in the study. The RNFL thickness average analysis program was used to evaluate mean superior, inferior, temporal, and nasal thickness. The data for all clock quadrants (12 values averaged) were identified as the overall RNFL. The retinal thickness analysis program was used to evaluate macular scans. Data were compared using the Man n-Whitney U test. The mean age ( standard deviation) was 35,43years. RESULTS: There were 13 eyes with amblyopia; this group had visual acuity 0,1 logMAR or better in the best eye. OCT parameters including the RNFL thickness in all quadrants, overall RNFL thickness and macular thickness showed no significant differences between the two groups (p >0,5). CONCLUSION: Assessment of RNFL thickness and macular thickness with OCT revealed no difference between the two eyes of patients with unilateral amblyopia.

The cell of origin of human retinoblastoma / 中华眼底病杂志

The debate on the cell of origin of human retinoblastoma lasted for more than one century.In the recent issue of "cell",David Cobrinik's group shows that L/M cone precursors are the most likely answer as they have an intrinsic circuitry,including murine double minute 2 (MDM2),N-myc,the nuclear receptors retinoid X receptor and thyroxine receptor 2,making them extremely sensitive to transformation following retinoblastoma gene inactivation.

Dosage relevance of trace PFD with toxicity in rabbit retina / 吉林大学学报(医学版)

Objective Through pathological and histological examination on retina to research the dosage relevance of trace PFD with toxicity in rabbit retina,and provide experimental reference basis for clinical practice.Methods Fourty eight eyes from 24 experimental rabbits were randomly divided into experimental group(36 eyes) and control group(12 eyes).The experimental one was divided into 3 groups,12 eyes in each group.The surface of rabbit retina was directly injected with 30,50,and 100 ?L liquids of PFD and BSS.The conditions of rabbit retina were observed under ophthalmoscope every day after the liquid injection.The sections of retina tissue were observed under transmission electron microscope in each experimental and control groups at the 4th,7th,14th and 21th day after injection.Results All samples were normal by ophthalmoscope examination while no pathological change of retina was found at various time points .At the 4th day,none substantial damage had been made in any dosage groups by transmission electron microscope examination except for 100 ?L group.Only one retina of 100 ?L group showed that the space around cell nucleus broadened appreciably,slightly atactic nucleus and slightly compact cytoplasm.It showed some early changes.From the 7th day,similar pathological changes were found: damage on outer segments of light receptor and outer plexiform layer,properties changes of light receptor,forming of vesicles of inner nuclear cells,damage of ganglion cell,dying of inside retina,actions of gulping cells in retina,swallow of film plates by pigment epithelial cell of retina,and dropping of top fine hair. But the retina of control group had no pathological changes.Conclusion Trace PFD exists in eyes.There is no relevance between poisonous development of retina and remaining dosage of PFD.However,large remaining of PFD can lead to retina toxicity early.

Optimal laser energy for laser induced chorioretinal venous anastomosis in the treatment of experimental branch retinal vein occlusion / 中华眼底病杂志

Objective To inspect the rate of success of anastomosis and tissue damage with different power levels of photocoagulation in the treatment of experimental branch retinal vein occlusion (BRVO) by laser induced chorioretinal venous anastomosis. Methods Forty pigmented rabbits (80 eyes) were divided into four groups in random, and 10 (20 eyes) in each. Chroioretinal venous anastomosis was attempted to create using the krypton red laser with 4 different power levels (group A: 400 mW,group B: 600 mW,group C: 800 mW,group D: 1000 mW) in these animals in which BRVO had previously been created photodynamically. Fundus photography and fundus fluorescein angiography were performed at various times after the treatment and histological examination was taken at the end of the study. Results The model of BRVO was successfully set up. At the lowest power of 400 mW there was an absence of anastomosis formation and the damage to the retina and choroid was mild, Bruch′s membrane showed no evidence of rupture. At the power levels of 600 mW and 800 mW an anastomosis formed in 15% and 55% respectively and the damage was medium in degree. At the highest power level of 1 000 mW a 80% rate of success was obtained, however, the damage to the retina and choroid tended to be severe. The difference of the rate of success of anastomosis between different groups was highly significant ( P =0 001), the difference between group B and group C was also highly significant ( P BC =0.008), and the difference between group A and group B, group C and group D was not significant ( P AB =0 072、 P CD =0 091). Conclusion The optimal power level of krypton red laser induced chorioretinal venous anastomosis is 800 mW, 0.1 s, 50 ?m in our study.

Photic damage of retina / 眼科

Examinations by fluoroscence fundus angiography were given to 4 patients suffered from photic damage of retina. The injuring macular regions of these cases were of the characteristics of the disappearrance of the capillary arc, the enlargement of the low-fluorescence-intensity region in the pigment epithelium and the exusion of circular fluorescein. The treatments with vasodiators, Vit E, Vit C and corticosteroid were effective in these cases.