Prospective evaluation of the effectiveness of combined treatment of macular edema secondary to retinal vein occlusion with intravitreal bevacizumab and dexamethasone implants / Estudo intervencionista prospectivo para avaliar a eficácia da associação do bevacizumabe intravítreo ao implante de dexametasona para edema macular secundário à oclusão da veia retiniana

ABSTRACT Purpose: To evaluate the effectiveness of in­­­travitreal bevacizumab injections following a single dexamethasone implant in the treatment of macular edema secondary to branch and central retinal vein occlusion. Methods: This was a prospective interventional non-comparative study, 44 eyes of patients with naïve macular edema related to branch and central retinal vein occlusion were treated with a dexamethasone implant. Patients were followed-up at four-week intervals from the second to the sixth month. If persistent or recurrent macular edema occurred during this period, the patient was treated with intravitreal bevacizumab injections on an as-needed basis. The outcome measures were best-corrected visual acuity and central macular thickness changes. Results: The mean best-corrected visual acuity changed from 0.97 ± 0.33 LogMAR at baseline to 0.54 ± 0.40 at the six-month post-implant examination (p<0.00001). Improvement ≥3 Snellen lines were seen in 20 eyes (45.54%). The mean central macular thickness at baseline was 670.25 ± 209.9 microns. This had decreased to 317.43 ± 112.68 microns at the six-month follow-up (p<0.00001). The mean number of intravitreal bevacizumab injections received in the six months post-implant was 2.32. The mean time from dexamethasone implant to first anti-VEGF injection was 3.45 months. Conclusions: Intravitreal bevacizumab injections following a single dexamethasone implant were found to improve best-corrected visual acuity and central macular thickness in patients with macular edema due to branch and central retinal vein occlusion at six months, with few intravitreal injections required.

RESUMO Objetivo: Avaliar a eficácia da combinação de in­jeções intravítreas de bevacizumabe em olhos com edema macular secundário à oclusão de ramo e da veia central da retina após um único implante de dexametasona. Métodos: Foi realizado um estudo prospectivo intervencionista não comparativo com 44 olhos de pacientes com edema macular relacionado à oclusão de ramo e veia central da retina, sem tratamento prévio e tratados com um único implante de dexametasona, que foram acompanhados em intervalos de quatro semanas do segundo ao sexto mês. Se fosse constatado edema macular persistente ou recorrente durante esse período, os pacientes eram tratados com injeções intravítreas de bevacizumabe em um regime ajustado conforme a necessidade. Foram estudadas a melhor acuidade visual corrigida e alterações da espessura macular central. Resultados: A média da melhor acuidade visual corrigida mudou de 0,97 ± 0,33 LogMAR iniciais para 0,54 ± 0,40 no exame de 6 meses (p<0,00001). Vinte olhos (45,54%) melhoraram 3 linhas de Snellen ou mais. A média da espessura macular central inicial foi de 670,25 ± 209,9 μm e diminuiu para 317,43 ± 112,68 μm na visita de 6 meses (p<0,00001). O número médio de injeções intravítreas de bevacizumabe em 6 meses foi de 2,32 e o tempo médio entre o implante de dexametasona e a primeira injeção de anti-VEGF foi de 3,45 meses. Conclusão: Injeções intravítreas de bevacizumabe após um único implante de dexametasona podem proporcionar um aumento da melhor acuidade visual corrigida e diminuição da espessura macular central aos 6 meses em pacientes com edema macular devido à oclusão de ramo e da veia central da retina, com poucas injeções intravítreas.

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)

ETDRS panretinal photocoagulation combined with intravitreal ranibizumab versus PASCAL panretinal photocoagulation with intravitreal ranibizumab versus intravitreal ranibizumab alone for the treatment of proliferative diabetic retinopathy / Panfotocoagulação retiniana a laser padrão ETDRS associado a injeção intravítrea de ranibizumabe versus panfotocoagulação retiniana a laser padrão PASCAL associado a injeção intravítrea de ranibizumabe versus somente injeção intravítrea de ranibizumabe para o tratamento da retinopatia diabética proliferativa

ABSTRACT Purpose: To compare visual acuity, macular thickness, and the area of active neovascularization based on fluorescein angiography outcomes associated with standard single-spot panretinal photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS) pattern combined with intravitreal ranibizumab injection versus multiple-spot full scatter (PASCAL) panretinal photocoagulation combined with intravitreal ranibizumab injection versus intravitreal injection alone in patients with proliferative diabetic retinopathy. Methods: Patients with proliferative diabetic retinopathy and no prior laser treatment were randomly assigned to receive three different types of treatment. Panretinal photocoagulation in the ETDRS group was administered in two sessions (weeks 0 and 2), and panretinal photocoagulation in the PASCAL group was administered in one session (week 0). Intravitreal injection of ranibizumab was administered at the end of the first laser session in both the ETDRS and PASCAL groups and at week 0 in the intravitreal injection group. Comprehensive ophthalmic evaluations were performed at baseline and every 4 weeks through week 48. Results: Thirty patients (n=40 eyes) completed the 48-week study period. After treatment, best-corrected visual acuity was significantly (p<0.05) improved at all follow-up visits in the group receiving intravitreal injection alone, at all but week 4 in the ETDRS group, and at all but weeks 4 and 8 for the PASCAL group. A significant decrease in central subfield macular thickness was observed in the PASCAL group at weeks 4, 8, and 48; only at week 48 in the intravitreal injection group; and never in the ETDRS group. There was no significant difference among the three treatment groups with respect to change from baseline to week 48 in best-corrected visual acuity, central subfield macular thickness, or fluorescein leakage from active neovascularization in best-corrected visual acuity, central subfield macular thickness, or fluorescein leakage from active neovascularization. Conclusions: Intravitreal injection alone or combined with single- or multiple-spot panretinal photocoagulation yielded similar outcomes with respect to mean change in best-corrected visual acuity, central subfield macular thickness, and fluorescein leakage from active neovascularization at up to one-year of follow-up. All subjects provided written informed consent to participate (NCT02005432 in clinicaltrials.gov).

RESUMO Objetivo: Comparar as medidas de acuidade visual, espessura macular central e área de neovasos ativos na an­giofluoresceinografia submetidos a panfotocoagulação retiniana padrão ETDRS associado a injeção intravítrea de ranibizumabe versus panfotocoagulação padrão PASCAL associado a injeção intravítrea de ranibizumabe versus somente injeção intravítrea de ranibizumabe em pacientes com retinopatia diabética pro­liferativa. Métodos: Pacientes com retinopatia diabética proliferativa e virgens de tratamento, randomicamente divididos nas três diferentes terapias retinianas. Panfotocoagulação no grupo ETDRS em 2 sessões (semanas 0 e 2) e no grupo PASCAL, na semana 0. Injeção intravítrea de ranibizumabe realizado ao fim da primeira sessão de laser em ambos os grupos: ETDRS e PASCAL, e na semana 0 no grupo injeção intravítrea de ranibizumabe. Avaliações oftalmológicas, tomografia de coerência óptica e angiofluoesceinografia realizados na visita basal e a cada 4 semanas por 48 semanas. Resultados: Trinta pacientes (n=40 olhos) completaram as 48 semanas de seguimento. Após o tratamento, a acuidade visual melhorou significantemente em todas a visitas no grupo injeção intravítrea de ranibizumabe (p<0,05); em todas exceto na semana 4 no grupo ETDRS, em todas exceto nas semanas 4 e 8 no grupo PASCAL. Redução significativa na espessura do subcampo central foi evidenciada no grupo PASCAL nas semanas 4, 8 e 48; somente na semana 48 no grupo injeção intravítrea de ranibizumabe, e em nenhuma visita no grupo ETDRS. Redução também na área de neovasos ativos em todas as visitas em todos os grupos. Não houve diferença significante entre os três grupos com relação a mudança media na medidas de acuidade visual, espessura macular central ou área de neovasos ativos da visita inicial para a semana 48. Conclusões: Somente IVB ou este associado a panfotocoagulação ETDRS ou PASCAL, apresentaram efeitos semelhantes em relação a medidas de acuidade visual, espessura do subcampo central e área de neovasos ativos no decorrer de 48 semanas de seguimento.

Treatment of Radiation Retinopathy with Intravitreal Injection of Ranibizumab (Lucentis®).

To report a treatment of radiation retinopathy in a patient exposed to ionizing radiation for a period of 2 years. A 26-year-old female patient with no comorbidities diagnosed with myelodysplasia confirmed by bone marrow biopsy. She presented a complaint of bilateral progressive visual acuity reduction. At the ophthalmologic examination, she presented alterations suggestive of radiation retinopathy as well as macular thickness to optical coherence tomography (OCT) of over 500 µm. The patient underwent intravitreal injection (0.05 mL) of ranibizumab (Lucentis®) monthly in both eyes and follow-up through visual acuity and OCT examination. She presented reduction of macular edema as well as a slight improvement of visual acuity. In this case, the treatment of radiation retinopathy with intravitreal injection of ranibizumab (Lucentis) was relatively useful, with a slight improvement of visual acuity, due to the regression of macular edema, not being curative.

The changes of macular blood flow density in patients of macular telangiectasis type 1 with macular edema before and after the treatment of anti-vascular endothelial growth factor / 中华眼底病杂志

Objective To observe the changes ofmacular blood flow density in patients ofmacular telangiectasis type 1 (Mac-Tel type 1) with macular edema before and after the treatment of anti-VEGF.Methods A retrospective clinical study.From January 2016 to December 2017,14 Mac-Tel type 1 patients (14 eyes) diagnosed in Nanjing Medical University Eye Hospital were included in the study.There were 6 males (6eyes) and 8 females (8 eyes),with the mean age of 35.3± 9.3 years.All patients underwent BCVA and OCT angiography examinations.The BCVA examination was performed using the Snellen visual acuity chart,which was converted into logMAR visual acuity.All the patients were received anti-VEGF injection treatment once a month for 3 consecutive months.The OCTA scanning region in the macular area was 3 mm × 3 mm.Macular blood flow density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP),the vessel density within a 300 μm width ring surrounding the foveal avascular area (FD-300) and central macular thickness (CMT)were measured in all eyes.Paired samples t-test and Pearson correlation analysis were used in this study.Results At the baseline,logMAR BCVA was 0.69 ± 0.07,CMT was 468.43 ± 26.59 μm,SCP blood flow density was (50.99± 1.19)％,DCP blood flow density was (43.79± 1.44)％,FD-300 was (50.73 ± 1.16)％.Compared with the baseline,there were significant differences between logMAR BCVA,CMT,DCP blood flow density and FD-300 in 1 week,1 month,3 months after treatment and 2 months after cessation of treatment (logMAR BCVA:t=6.77,13.30,16.99,9.51;P=0.00,0.01,0.00,0.01.CMT:t=6.99,15.88,26.10,6.50;P=0.00,0.01,0.01,0.00.DCP:t=6.75,8.61,15.12,7.63;P=0.00,0.01,0.01,0.00.FD-300:t=11.86,13.08,14.36,4.41;P=0.00,0.01,0.01,0.03).There was no significant difference in blood flow density of SCP between baseline and 2 months after cessation of treatment (t=1.36,P=0.19),but there was significant difference at the other time points after treatment (t=5.50,6.84,6.27;P=0.00,0.01,0.01).The Pearson's correlation analysis showed that there was a significant positive correlation between FD-300 and CMT (r2=0.54,P=0.04).Conclusions There is no significant change in the SCP blood flow density in the patients of Mac-Tel type 1 with macular edema,while the DCP blood flow density decreased and FD-300 increased.After anti-VEGF treatment,DCP blood flow density increased and FD-300 decreased.FD-300 is positively correlated with CMT.

The alterations of microvascular structure in branch retinal vein occlusion eyes before and after anti-vascular endothelial growth factor drug therapy / 中华眼底病杂志

Objective To observe the alterations ofmicrovascular structure in patients with macular edema (ME) associated with branch retinal vein occlusion (BRVO) before and after anti-VEGF drug therapy.Methods A retrospective case study.Thirty-two eyes of 32 patients with unilateral BRVO-ME at Department of Ophthalmology in Beijing Hospital during November 2016 to June 2018 were enrolled in this study.There were 14 males (14 eyes) and 18 females (18 eyes),with the mean age of 57.81 ± 10.58 years,and the mean course of the disease of 12.13 ± 7.13 d.The affected eyes was defined as the eyes with BRVO-ME.All the affected eyes received intravitreal anti-VEGF drug injections (3+PRN).BCVA and OCT angiography (OCTA) were performed on the BRVO and fellow eyes before and after intravitreal anti-VEGF drug injections.The scanning region in the macular area was 3 mm × 3 mm.Macular blood flow density in the superficial capillary plexus (SCP) and deep capillary plexus (DCP),macular hemodynamics parameters [foveal avascular area (FAZ) area,perimeter (PERIM),acircularity index (AI) and vessel density within a 300um width ring surrounding the FAZ (FD-300)] and central retinal thickness (CRT) were measured in all eyes.Paired samples t-test and Univariate Linear Regression were used in this study.Results Comparing with fellow eyes,the mean macular blood flow density measured in the entire scan was lower in BRVO-ME eyes in the SCP (t=6.589,P=0.000) and DCP (~9.753,P=0.000),PERIM (t=4.054,P=0.000)),AI enlarged in BRVO-ME eyes (t=4.988,P=0.000),FD-300 was lower in BRVO-ME eyes (t=2.963,P=0.006),FAZ area enlarged in BRVO-ME eyes (t=0.928,P=-0.361).The blood flow density in the DCP was the parameter most significantly correlated with BCVA and FAZ area (r=0.462,-0.387;P＜.05).After 3 intravitreal injections of anti-VEGF drug,the CRT and FD-300 decreased,BCVA increased (t=9.865,3.256,-10.573;P＜0.05),PERIM and AI was not changed significantly (t=0.520,2.004;P＞0.05).The blood flow density in the SCP decreased (t=2.814,P＜0.05),but the blood flow density in the DCP was not changed significantly (t=0.661,P=-0.514).Contrarily,comparing with after 1 antiVEGF drug injection,the blood flow density in the DCP increased after 2 anti-VEGF drug injections (t=3.132,P＜0.05).FAZ area enlarged in BRVO-ME eyes (t=5.340,P＜0.001).Comparing with last anti-VEGF drug injection,FAZ area enlarged after every anti-VEGF drug injection (t=2.907,3.742,2.203;P＜0.05).Conclusions In BRVO-ME eyes,the blood flow density in the SCP and DCP are decreased.The blood flow density in the DCP is positively correlated with BCVA and negatively correlated with FAZ area.After antiVEGF drug therapy,the blood flow density is decreased in the SCP and increased in the DCP,FAZ area enlarged gradually,PERIM and AI are not changed significantly.

Changes of blood flow density in patients with idiopathic choroidal neovascularization treated with anti-vascular endothelial growth factor / 中华眼底病杂志

Objective To assess changes of blood flow density of idiopathic choroidal neovascularization (ICNV) treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF).Methods Retrospective case analysis.Sixteen eyes of 16 patients with ICNV diagnosed with FFA and OCT were included in this study.Among them,12 were female and 4 were male.The mean age was 33.94±9.83 years.The mean course of diseases was 5.13 ±4.44 weeks.The BCVA,indirect ophthalmoscope,OCT and OCT angiography (OCTA) were performed at the first diagnosis in all patients.The BCVA was converted to logMAR.The macular fovea retinal thickness (CMT) was measured by OCT,and the selected area of CNV (CSA) and flow area of CNV (CFA) were measured by OCTA.The mean logMAR BCVA,CMT,CSA and CFA were 0.336±0.163,268.500±57.927 μm,0.651 ±0.521 mm2,0.327±0.278 mm2,respectively.All patients were treated with intravitreal ranibizumab (IVR,10 mg/ml,0.05 ml).Follow-up results including the BCVA,fundus color photography,OCT and OCTA were obtained 1 month after treatment.To compare the changes ofBCVA,CMT,CSA,CFA of ICNV treated with anti-VEGF.Pearson method was used to analyze the correlation between logMAR BCVA and CMT,CSA and CFA before and after the treatment.Results One month after treatment,the average logMAR BCVA,CMT,CSA and CFA were 0.176±0.111,232.500± 18.910 μm,0.420±0.439 mm2,0.215 ± 0.274 mm2.The mean logMAR BCVA (t=5.471,P＜ 0.001),CMT (t=2.527,P=0.023),CSA (t=4.039,P=0.001),CFA (t=4.214,P=0.001) significantly decreased at 1 month after injection compared to baseline,and the difference had statistical significance.The results of correlation analysis showed that the post-logMAR BCVA was moderately positively correlated with pre-CSA and post-CSA (r=0.553,0.560;P=0.026,0.024),and strongly correlated with pre-CFA and post-CFA (r=0.669,0.606;P=0.005,0.013),but not correlated with preCMT and post-CMT (r=0.553,0.560;P=0.026,0.024).Conclusion The blood flow density of ICNV measured by OCTA were significantly decreased in the treatment of anti-VEGF drugs.

Contrast observation of optical coherence tomography angiography between neovascular age-related macular degeneration and myopic choroidal neovascularization before and after intravitreal anti-vascular endothelial growth factor treatment / 中华眼底病杂志

Objective To compare the features of OCT angiography (OCTA) between neovascular agerelated macular degeneration (nAMD) and myopic ehoroidal neovascularization (mCNV) patients before and after intravitreal anti-VEGF treatment.Methods A prospective cohort study.Twenty-nine patients (37 eyes) with nAMD (19 males and 10 females,aged 68.20±8.76) and 31 patients (34 eyes) with mCNV (9 males and 22 females,aged 43.10± 11.80,with the mean diopter of-9.71 ± 1.20 D) from Department of Ophthalmology,West China Hospital of Sichuan University during May and December 2017 were included in this study.Ranibizumab or Conbercept (0.5 mg/0.05 ml) was intravitreally injected in all eyes.The patients were follow-up for 3-6 months.The OCTA was conducted before treatment and 1 day,1 week,1 month and 3-6 months after treatment.In order to ensure that the scanning position was the same,the tracking mode was adopted for each scanning.According to the OCTA images,the lesion area,parafoveal superficial vessel density and perfusion area were measured and analyzed contrastively between nAMD and mCNV patients.Results The mean lesion area before and 1 month after treatment in nAMD patients were 0.38± 1.87 mum2 and 0.06±0.12 mm2,while in mCNV patients,those were 0.26± 1.06 mm2 and 0.03 ± 0.05 mm2,respectively.There were statistically significant differences (Z=4.181,4.475;P＜0.001) in CNV lesion area before and 1 month after treatment between nAMD and mCNV patients.Compared with those before treatment,the absolute change (Z=1.853,P=0.064) and the percentage changes (t=2.685,P=0.010) of CNV lesion area l month after treatment in nAMD and mCNV patients show a statistical meaning.There were significantly decreases in both parafoveal superficial vessel density (F=8.997,P=0.003) and perfusion area (F=7.887,P=0.015) 3 months after treatment in nAMD patients,while decreases in parafoveal superficial vessel density (F=11.142,P=0.004) and perfusion area (F=7.662,P=0.013) could be detected 1 day after treatment in mCNV patients,before rising 1 month after treatment.Conclusions There are significantly differences in lesion area before and after the treatment of intravitreal anti-VEGF between nAMD and mCNV patients by OCTA examination.Moreover,the changes of both parafoveal superficial vessel density and perfusion area after anti-VEGF treatment are statistically different in two groups.

The effect of conbercept combined with 577 nm subthreshold micropulse laser photocoagulation on diabetic macular edema / 中华眼底病杂志

Objective To observe the effect ofconbercept combined with 577 nm subthreshold micropulse laser photocoagulation on diabetic macular edema (DME).Methods A prospective randomized controlled clinical study.From June 2016 to June 2017,68 eyes of 68 patients with DME diagnosed in Central Theater Command General Hospital were enrolled in the study.The patients were randomly assigned to two different treatment groups:36 eyes (36 patients) in the conbercept combined with 577 nm subthreshold micropulse lase group (combined treatment group) and 32 eyes (32 patients) in conbercept group (drug treatment group).All patients received three initial intravitreous injection of conbercept and re-treatment was performed according to the criteria which has been disigned before.BCVA was measured by ETDRS charts.The central macular thickness (CMT),total macular volume (TMV) were measured by Topcon 3D-OCT 2000.The BCVA,CMT and TMV in the combined treatment group and the drug treatment group were 57.9 ± 12.4 letters,427.8± 129.4 μm,10.14± 1.50 mm3 and 59.0± 16.0 letters,441.0 ±135.7 μm,10.43 ±2.10 mm3,respectively.There was no significant difference (t=0.321,0.410,0.641;P=0.749,0.683,0.524).The follow-up period was more than 12 months.The changes of BCVA,CMT and TMV were compared between the two groups.Comparison ofBCVA,CMT,TMV before and after treatment in and between groups using repeated measures analysis of variance.Results The average annual injection times was 5.8 ± 1.9 in the combined treatment group and 8.5± 2.4 in the drug treatment group.The difference was statistically significant (t=5.12,P=0.000).The BCVA in the 3rd,6th,9th and 12th month were 64.9± 11.1,65.6± 10.5,67.0± 10.8,66.6± 10.7 letters and 65.7± 15.8,66.9 ± 15.7,66.4 ± 13.0,67.3 ± 16.4 letters,respectively,and there were significant differences compared with BCVA before treatment (F=34.234,10.137;P=0.000,0.000).The CMT were 335.2± 105.9,352.6± 106.6,336.2± 120.8,305.9±97.0 μm and 323.9±92.8,325.5±90.2,327.6± 108.2,312.2± 106.8 μm,respectively.The TMV were 9.20± 1.08,9.26± 1.20,9.20± 1.63,9.05± 1.18 mm3 and 9.19± 1.21,9.35± 1.69,9.09± 1.20,8.92± 1.10 mm3,respectively.Compared with the CMT (F=12.152,12.917;P=0.000,0.000) and TMV (F=11.198,11.008;P=0.000,0.000) before treatment,the differences were statistically significant.Conclusion Conbercept combined with 577 nm subthreshold micropulse laser and conbercept can effectively reduce CMT,TMV and improve BCVA in patients with DME,but combination therapy can reduce the injection times of conbercept.

Intravitreal aflibercept versus photodynamic therapy in Chinese patients with neovascular age-related macular degeneration: outcomes of the SIGHT study / 中华眼底病杂志

Objective To assess the efficacy and safety ofintravitreal aflibercept injection (IAI) compared with photodynamic therapy (PDT) in the treatment of Chinese patients with predominantly classic subfoveal choroidal neovascularization (CNV) lesions secondary to neovascular age-related macular degeneration (nAMD).Methods A randomized,double-blind,multi-center phase-3 clinical trial lasting for 52weeks (from December 2011 to August 2014).Subjects were randomized in a 3:1 ratio to either IAI group or PDT-to-IAI group.Subjects in the IAI group received 2 mg IAI at baseline and at week 4,8,16,24,32,40,48,with sham injection at week 28,36.Subjects in the PDT-to-IAI group were forced to receive PDT once at baseline and more time at week 12,24 if PDT retreatment conditions were met.Sham injections were given in PDT-to-IAI group at baseline and at week 4,8,16 and 24,followed by 2 mg IAI at week 28,32,36,40,48.The primary outcome of efficacy were the change in mean Best Corrected Visual Acuity (BCVA) from baseline to week 28,and that of week 52.Safety evaluation included the percentage of subjects who suffered treatment emergent adverse events (TEAEs).Results Among the 304 subjects enrolled,there were 228 and 76 cases in IAI group and PDT-to-IAI group respectively.At week 28,the changes of mean BCVA in IAI group,PDT-to-IAI group compared to baseline were +14.0,+3.9 letters,respectively.At week 52,the changes of mean BCVA in two groups were + 15.2,+8.9 letters respectively with the difference of +6.2 letters (95％CI 2.6-9.9,P=0.000 9).At week 52,the mean foveal retinal thickness in the two groups decreased by-189.6,-170.0 μm,respectively.Subjects with the most BCVA increase in IAI group were those aged ＜65,and those with active CNV lesion area ＜50％ of total lesion area.The most common TEAEs in IAI group and PDT-to-IAI group are macular fibrosis [11.8％ (27/228),6.6％ (5/76)] and BCVA decline [6.6％ (15/228),21.1％ (16/76)].There were 3 cases of arterial thromboembolic events defined in the antiplatelet experimental collaboration group,but all were considered unrelated to interventions.Conclusions The efficacy of aflibercept is superior to that of PDT in nAMD patients in China.The therapeutic effect of aflibercept persisted to week 52 in all subjects.The rate of adverse events was consistent with the safety data of aflibercept known before.

Evaluation of macular visual function in patients with myopic choroidal neovascularization before and after intravitreal injection of conbercept / 中华眼底病杂志

Objective To evaluate the macular visual function of patients with myopic choroidal neovascularization (MCNV) before and after intravitreal injection of conbercept.Methods A prospective,uncontrolled and non-randomized study.From April 2017 to April 2018,21 eyes of 21 patients diagnosed as MCNV in Shanxi Eye Hospital and treated with intravitreal injection of conbercept were included in this study.There were 9 males (9 eyes,42.86％) and 12 females (12 eyes,57.14％),with the mean age of 35.1 ± 13.2 years.The mean diopter was-11.30 ± 2.35 D and the mean axial length was 28.93 ± 5.68 mm.All patients were treated with intravitreal injection of conbercept 0.05 ml (1+PRN).Regular follow-up was performed before and after treatment,and BCVA and MAIA micro-field examination were performed at each follow-up.BCVA,macular integrity index (MI),mean sensitivity (MS) and fixation status changes before and after treatment were comparatively analyzed.The fixation status was divided into three types:stable fixation,relatively unstable fixation,and unstable fixation.The paired-sample t-test was used to compare BCVA,MI and MS before and after treatment.The x2 test was used to compare the fixation status before and after treatment.Results During the observation period,the average number of injections was 3.5.The logMAR BCVA of the eyes before treatment and at 1,3,and 6 months after treatment were 0.87±0.32,0.68±0.23,0.52±0.17,and 0.61 ±0.57,respectively;MI were 89.38 ± 21.34,88.87 ± 17.91,70.59 ± 30.02,and 86.76 ± 15.09,respectively;MS were 15.32 ± 7.19,21.35 ± 8.89,23.98 ± 11.12,22.32 ± 9.04 dB,respectively.Compared with before treatment,BCVA (t=15.32,18.65,17.38;P＜0.01) and MS (t=4.08,3.50,4.26;P＜0.01) were significantly increased in the eyes 1,3,and 6 months after treatment.There was no significant difference in the MI of the eyes before treatment and at 1,3,and 6 months after treatment (t=0.60,2.42,2.58;P＞0.05).Before treatment and at 1,3,and 6 months after treatment,the proportion of stable fixation were 28.57％,38.10％,38.10％,33.33％;the proportion of relatively unstable fixation were 47.62％,47.62％,52.38％,57.14％ and the proportion of unstable fixation were 23.81％,14.28％,9.52％,9.52％,respectively.The proportion of stable fixation and relatively unstable fixation at 1,3 and 6 months after treatment were higher than that before treatment,but the difference was not statistically significant (x2=1.82,1.24,1.69;P＞0.05).Conclusion BCVA and MS are significantly increased in patients with MCNV after intravitreal injection of conbercept.

Efficacy and related factors of intravitreal injection with conbercept for retinopathy of premature / 中华眼底病杂志

Objective To observe the effect ofintravitreal injection ofconbercept in the treatment of retinopathy of premature (ROP) and to analyze the factors related to the therapy.Methods A retrospective study.A total of 57 patients (57 eyes) with pre-threshold type 1 (30 patients,30 eyes),threshold ROP (21 patients,21 eyes) and acute aggressive posterior ROP (APROP,6 patients,6 eyes)) from premature infants by retinal screening in Henan Provincial People's Hospital during October 2017 and June 2018 were enrolled in this study.All children were received routinely intravitreal injected 10 mg/ml conbercept 0.025 ml (0.25 mg) within 24 hours after diagnosis.Fundus examination was performed 7 days after injection.The interval of examination was 1-3 weeks according to fundus conditions.The mean follow-up was 30.1 ± 4.6 weeks.For patients with relapse or no response to treatment,repeated intravitreal injection of conbercept or laser photocoagulation therapy was given.The retinal blood vessels of the affected eyes were observed.Logistic stepwise regression analysis was used for the correlation test of multiple factors.Results Among 57 eyes,49eyes and 8 eyes were treated with 1 or 2 times of intravitreal injection of conbercept.After 24 weeks of treatment,in 57 eyes,26 eyes were cured (45.6％),22 eyes improved (38.6％),8 eyes relapsed (14.0％),and 1 eye aggravated (1.8％).The recurrence time was 12.9± 4.5 weeks after the first injection,and the corrected gestational age was 49.0±6.7 weeks.There were significant differences in initial injection time,lesion range among the cure,improved and recurrence eyes (F=5.124,7.122;P＜0.01,＜ 0.01).Parameters of ROP condition,including ROP diagnosis (pre-threshold type 1,threshold and APROP),zone (zone 1 and 2),stage (stage 2 and 3) and plus lesions,were significant different among the cure,improved and recurrence eyes (x2=l 1.784,14.100,6.896,9.935;P＜0.01,＜0.01,＜0.05,＜0.01).Logistic stepwise regression analysis showed that the recurrence rate was correlated with ROP zone,more likely recurrence at zone 1 than zone 2 (Wald=9.879,OR=27.333,P=0.002).No injection-related complications such as endophthalmitis,cataract and glaucoma were found during treatment and follow-up period.Conclusions Intravitreal injection ofconbercept is effective in the treatment of ROP without obvious adverse reactions.Lesion zoning is associated with recurrence after treatment.

The assessment of diabetic macular ischemia and the influence of intravitreal anti-vascular endothelial growth factor therapy to diabetic macular ischemia / 中华眼底病杂志

Diabetic macular ischemia (DMI) is one of the manifestation of diabetic retinopathy (DR).It could be associated with diabetic macular edema (DME),which may affect the vision of DR patients.FFA is the gold standard for the diagnosis of DMI,but with the advent of OCT angiography,a more convenient and diversified method for the evaluation of DMI has been developed,which makes more and more researchers start to study DMI.Intravitreal injection of anti-VEGF has become the preferred treatment for DME.When treating with DME patients,ophthalmologists usually avoid DMI patients.But if intravitreal anti-VEGF should be the contradiction of DME is still unclear.To provide references to the research,this article summarized the risk factors,assessment methods and influence of DMI.This article also analyzed the existing studies,aiming to offer evidences to a more reasonable and effective treatment decision for DME individual.

Current status and progress of recurrence of retinopathy in prematurity after intravitreal injection with anti-vascular endothelial growth factor drugs / 中华眼底病杂志

Intravitreal injection of anti-VEGF drugs for the treatment of retinopathy of prematurity(ROP) is a hot topic of research, and it can be used to treat the ROP (Ⅰzone). The current anti-VEGF drugs include bevacizumab, ranibizumab, aflibercept and conbercept, etc. However, in recent years, several studies have confirmed that anti-VEGF drugs have an increased recurrence rate and a longer recurrence time than conventional laser photocoagulation therapy. The follow-up period should be extended and repeated injections may be required. Due to the lack of large-scale prospective clinical studies, the recurrence rate, time window of recurrence, risk factors and treatment methods of various anti-VEGF drugs for ROP are still unclear. Anti-VEGF drugs in the treatment of ROP needs to accumulate more evidence-based medical evidence.

Current status and progress of recurrence of retinopathy in prematurity after intravitreal injection with anti-vascular endothelial growth factor drugs / 中华眼底病杂志

Intravitreal injection of anti-VEGF drugs for the treatment of retinopathy of prematurity (ROP) is a hot topic of research,and it can be used to treat the ROP (Ⅰ zone).The current anti-VEGF drugs include bevacizumab,ranibizumab,aflibercept and conbercept,etc.However,in recent years,several studies have confirmed that anti-VEGF drugs have an increased recurrence rate and a longer recurrence time than conventional laser photocoagulation therapy.The follow-up period should be extended and repeated injections may be required.Due to the lack of large-scale prospective clinical studies,the recurrence rate,time window of recurrence,risk factors and treatment methods of various anti-VEGF drugs for ROP are still unclear.Anti-VEGF drugs in the treatment of ROP needs to accumulate more evidence-based medical evidence.

The reactivation time in the treatment of AMD: a forgotten key parameter?

OBJECTIVE: Summarize and compare the available evidence on the reactivation times in patients with age-related macular degeneration treated with Ranibizumab (RNB). METHOD: Systematic review of studies that reported the reactivation time of patients (direct method) or the number of injections received in a certain period of follow-up (indirect method). RESULTS: Only 18 of 89 selected studies reported the average reactivation time of patients in a manifest form, without the need of any calculation. The average calculated, weighted reactivation time was 101.8 days with the direct method and 99.8 days in the indirect method (84 studies included). With both methods, it was found that the average reactivation time of the RCTs was between 2 and 3 weeks less than the average time identified in the observational studies. These differences are also reflected in the clinical results, there being a correlation between the number of doses received and the change in BCVA. The analysis of 11 comparative studies showed a difference in reactivation times between patients treated with RNB or Bevacizumab (BVZ). CONCLUSION: There are few direct studies of reactivation time, but calculation from the PRN dose number turns out to be a good approximation for retrospective study of the variable. The use of the PRN, with criteria not based on optical coherence tomography scans, delays the application of doses between 2 or 3 weeks, and patients suffer loss of clinical benefits. RNB enables patients to receive less injections than BVZ throughout treatment.

The effect of retinal thickness on the prognosis of long-term vision after the treatment of intravitreal injection of Conbercept combined with retinal laser photocoagulation for macular edema secondary to branch retinal vein occlusion / 中华眼底病杂志

Objective To observe the effect of macular retinal thickness (CMT) on the long-term visual prognosis after intravitreal injection of Conbercept combined with retinal laser photocoagulation for macular edema (ME) secondary to branch retinal vein occlusion (BRVO).Methods A retrospective non randomized controlled study.Forty-one patients (41 eyes) of ischemic BRVO secondary ME were included in the study.Among them,there were 23 males (23 eyes) and 18 females (18 eyes).The average age was (56.49±8.94) years.The best corrected visual acuity (BCVA) and optical coherence tomography were performed.The mean logMAR BCVA was 0.82±0.41,and the mean CMT was (512.61 ± 185.32) μrn.According to the CMT reduction value at 1 month after treatment,the eyes were divided into no response group and response group,each has 15 patients of 15 eyes and 26 patients of 26 eyes respectively.The age and sex composition of the two groups were not statistically significant (t=-0.298,-1.708;P=0.767,0.096),and the difference of frequency of injection was statistically significant (t=3.589,P=0.010),and there was no statistical difference between the patients with logMAR BCVA and CMT (t=2.056,-1.876;P=0.460,0.070).The average follow-up was 8 months.The logMAR BCVA on 6 months after treatment was defined as long term vision.The changes of long term vision and CMT on 1 and 6 months of two groups after treatment were observed.Pearson correlation analysis showed that the correlation between long-term vision and age,logMAR BCVA before treatment,CMT before treatment,frequency of injection,and CMT value decreased 1 month after treatment.The correlation of long-term visual acuity with age,sex,logMAR BCVA before treatment,CMT before treatment,number of drugs before treatment,CMT reduction at 1 month after treatment,integrity of ellipsoid band and integrity of external membrane (ELM) were analyzed by multiple regression analysis.Results On 1 month after treatment,the CMT of the eyes was lower than that before treatment (231.48± 177.99) μm,and the average integrity of ELM and ellipsoid were 0.56±0.50 and 0.41 ±0.50 respectively.On 6 months after treatment,the average logMAR BVCA of the eyes was 0.48 ± 0.34.The results of Pearson correlation analysis showed that the long-term vision was positively correlated with the logMAR BCVA before treatment and the number of CMT reduction and the number of drug injection at 1 month after treatment (P＜0.05);there was no correlation with age and CMT before treatment (P＞0.05).The results of multiple regression analysis showed that the long-term vision was associated with logMAR BVCA before treatment,CMT reduction,ELM integrity,and the number of times of injection (P＜0.05),and no correlation with age,sex,CMT before treatment and the integrity of the ellipsoid (P＞0.05).On the 6 months after treatment,the logMAR BCVA in the non-response group and the response group were 0.86±0.23 and 0.26±0.14,and the average CMT was respectively (398.93±104.87) and (255.15 ± 55.18) μrn,and the average injection times were respectively (2.53 ± 1.46) and (1.31 ± 0.74) times.The average logMAR BCVA,CMT and injection times of the two groups were statistically significant (t=10.293,5.773,3.589;P=0.000,0.000,0.001).No complications related to drug or intravitreal injection occurred in all patients.Conclusion The long-term vision of ME secondary to BRVO after intravitreal injection of Conbercept combined with retinal laser photocoagulation was associated with the decrease of CMT and the integrity of the ELM after 1 month of treatment,no correlation was found between CMT and ellipsoid integrity before treatment.

RNA-Seq analysis of gene expression profiling in human retinal vascular endothelial cells after anti-vascular endothecial growth factor treatment / 中华眼底病杂志

Objective To observe RNA-Seq analysis of gene expression profiling in human retinal vascular endothelial cells after anti-vascular endothecial growth factor (VEGF) treatment.Methods Cultured the retinal vascular endothelial cells in vitro and logarithmic growth phase cells were used for experiments.The cells were divided into VEGF group and VEGF combined with anti-VEGF drugs group.The VEGF group cells were treated with 50 ng/ml VEGF for 72 h to simulate the high VEGF survival conditions of vascular endothelial cells in diabetic retinopathy.VEGF combined with anti-VEGF drug group cells was treated with 50 ng/ml VEGF and 2.5 μg/ml anti-VEGF drugs for 72 h to imitate the microenvironment of cells following the anti-VEGF drugs treatment,and whole transcriptome sequencing approach was applied to the above two groups of cells through RNA-Seq.Now with biological big data obtained as a basis,to analyze the differentially expressed genes (DEGs).And through enrichment analysis to explain the differential functions of DEGs and their signal pathways.Results The gene expression profiles of the two groups of cells were obtained.Through analysis,328 DEGs were found,including 194 upregulated and 133 downregulated ones.The functions of DEGs were influenced by regulations over molecular biological process,cellular energy metabolism and protein synthesis,etc.Among these genes,SI,PRX and HPGD were related to protein synthesis,BIRCT to cellular apoptosis,and ABLIM 1 and CRB2 to retinal development,and ABCG 1,ABCA9 and ABCA12 were associated with the cholesterol of macrophage and the transfer of phospholipid.GO enrichment analysis showed that DEGs mainly act in three ways:regulating biological behavior,organizing cellular component and performing molecular function.Pathway enrichment analysis showed that gene expressions of the two cell groups were differentiated in ECM receptor pathway,and Notch,mitogen-activated protein kinase,transforming growth factor (TGF)-β and Wnt signal pathways.Among them,the gene expression in TGF-β signal pathway attracts most attention,where the DEGs,such as CAMK2B,COL3A1,CYGB,PTGER2 and HS6ST2,among others,were closely related to fibrosis process.Conclusion The anti-VEGF drugs may enhance the expression ofCAMK2B,COL3A1,CYGB,PTGER2 and others genes related to TGF-β signal pathway and aggravate retinal fibrosis disease.

Appropriate understanding the application of anti-vascular endothelial growth factor agents and laser photocoagulation for infants retinal vascular diseases / 中华眼底病杂志

Retinopathy ofprematurity,familial exudative vitreoretinopathy and Coats disease are the most common neonates and infants retinal vascular diseases,which may lead to severe visual damage because of either tractional retinal detachment caused by the proliferation of pathogenic neovascularization,or exudative retinal detachment due to the extremely leakage from abnormal retinal vessels.Classic treatment is retinal laser photocoagulation which could destroy these abnormal vessels or reduce non vascular areas to diminish the growth of new vessels,however the side effects induced by laser it self such as visual field damage,hemorrhage,retinal tear,fail to control the progression of the disease make the laser treatment hard to improve the vision of these young patients.Anti-vascular endothelial growth factor (VEGF) agents have been widely applied in various adult retinal and choroidal vascular diseases,they are even possible to replace the pan retinal photocoagulation in proliferative diabetic retinopathy,while there are still many unsolved problems in the applying in neonates and infants retinal vascular diseases,like dosage,timing,retreatment and systemic side effects.We should realize the importance of selecting the laser photocoagulation and anti-VEGF for neonates and infants retinal vascular diseases.

Analysis of factors associated with short-term elevation of intraocular pressure after ranibizumab intravitreal injection / 中华眼底病杂志

Objective To investigate the factors associated with short-term elevation ofintraocular pressure after ranibizumab intravitreal injection.Methods 292 eyes of 292 patients who were diagnosed retinopathy and suitable to receive ranibizumab intravitreal injection were enrolled in this prospective clinical study.There were 157 males and 135 females.193 patients diagnosed with age-related macular degeneration and 99 other retinopathy patients.Mean age of patients was 62.75 ± 13.74 years.All subjects underwent systemic and comprehensive ophthalmology examinations.The mean BCVA was 0.68± 0.47 logMAR.Mean basal intraocular pressure was 18.1 mmHg (1 mmHg=0.133 kPa).All patients received intravitreal injection with 0.05 ml of ranibizumab (0.5 mg).The intraocular pressure were measured by non-contact tonometer at 10,30,120 minutes and 1 day after injection in a sitting position.The patients were grouped by the changes ofintraocular pressure 10 minutes after injection.The elevation was more than 10 mmHg as elevation group and less than 10 mmHg as stable group.Analyze the possible related factors with elevation of intraocular pressure after ranibizumab intravitreal injection by comparing the different datum of two groups.Results The mean intraocular pressure were 23.8,20.5,19.9 and 17.4 mmHg at 10,30,120 minutes and 1 day after injection.The significant elevation level were 5.8,2.4,1.8,-0.7 mmHg compared with basal intraocular pressure.Among 292 eyes,intraocular pressure elevation in 68 eyes and stabled in 224 eyes.The age (Z=-0.732),gender (x2=1.929),right or left eye (x2=2.910),BCVA (Z=-0.039),diseases ((2=2.088) were no significant difference between two groups (P＞0.05).The injection number (Z=-2.413,P=0.001),basal intraocular pressure (Z=-3.405,P=0.016) and elevations after injection (Z=-11.501,-8.366,-5.135,-3.568;P＜0.01) were significantly different comparing two groups (P＜0.05).By logistic regression analysis,basal intraocular pressure was positively correlated with the elevation of intraocular pressure 10 minutes after injection (B=-0.844,OR=0.43,95％CI 0.24-0.76,P=0.004).Patients with higher basal intraocular pressure may occur intraocular pressure elevation after ranibizumab intravitreal injection much probably.Conclusions The factors associated with short-term elevation of intraocular pressure after ranibizumab intravitreal injection were basal intraocular pressure.The higher basal intraocular pressure,the higher risk to gain elevation of intraocular pressure after injection.