Retrospective study of an as required dosing regimen of intravitreal bevacizumab in neovascular age‐related macular degeneration in an Australian population

Purpose: To investigate the efficacy of intravitreal bevacizumab for the treatment of neovascular age‐related macular degeneration (AMD) using an as required dosing regimen. Methods: A retrospective study of 210 patients (231 eyes) with choroidal neovascularization resulting from neovasacular AMD. Patients were treated with 1.25 mg intravitreal bevacizumab at a vitreoretinal practice in Adelaide, South Australia. Patients were followed up at 2–4 weeks and then at 1‐month intervals; repeat injections were offered in the event of recurrence. Recurrence was defined as either a decrease of best‐corrected visual acuity or an increase in macular oedema, subretinal fluid or intraretinal fluid on optical coherence tomography, after complete or partial resolution in previous follow‐up visits. Patient data were collected for 12 months of follow up or until the patient's treatment was changed to ranibizumab. Results: Significant improvement in visual acuity and central retinal thickness was demonstrated at 1 month with an improvement of vision from logMAR equivalent 0.76 to 0.68 (P < 0.001) and a decrease of central retinal thickness from 306 µm to 244 µm (P < 0.001). This overall improvement was continued throughout the 12‐month follow‐up period; however, follow up was poor with 12‐month data available for only a small number of patients (7.8%). Ocular and systemic side‐effects were rare at 3.5% and 0.4%, respectively. Conclusion: Eyes with neovascular AMD treated with intravitreal bevacizumab for up to 12 months had significant functional and anatomical improvement. Further studies need to confirm the long‐term safety and efficacy of this treatment.     

Predictors of 1‐year visual outcome in neovascular age‐related macular degeneration following intravitreal ranibizumab treatment

Purpose: To describe predictors of visual outcome in patients treated with intravitreal ranibizumab for choroidal neovascularisation (CNV) in age‐related macular degeneration (AMD). Methods: Retrospective review of 279 patients with CNV in AMD who fulfilled MARINA/ANCHOR study eligibility criteria and were treated with repeated intravitreal injections of ranibizumab 0.5 mg in routine clinical practice, beginning with three initial injections at 4‐week intervals followed by individualized retreatment for the subsequent 9 months. Study parameters included best‐corrected visual acuity (BCVA) and morphological characteristics. Results: Mean BCVA relative to baseline was +4.7 (p < 0.0001), +4.2 (p < 0.0001)and ?0.4 (p > 0.667) Early Treatment Diabetic Retinopathy Study letters after 3, 6 and 12 months, respectively, after a mean of 5.1 injections when the proportion of patients with BCVA ≥70 letters had doubled compared with baseline. Predictive factors for BCVA ≤35 letters after 12 months were BCVA ≤35 letters at baseline and month 3 (p < 0.0001) while BCVA ≥70 letters at month 12 was associated with BCVA ≥70 letters at baseline and month 3 (p < 0.001) and with total lesion size <4 DA (p = 0.0147). Conclusion: Under a ranibizumab regimen with substantially fewer injections than with fixed four‐weekly injection regimens, BCVA was improved compared with the natural history of neovascular AMD, but did not achieve the visual gain observed in randomized clinical trials using fixed 4‐week retreatment. Visual acuity at month 3, after the initial fixed‐interval injections, was the strongest predictor of BCVA at month 12.     

Correlation between components of newly diagnosed exudative age‐related macular degeneration lesion and focal retinal sensitivity

Purpose: To analyse lesion components determining retinal sensitivity in microperimetry in eyes with newly diagnosed exudative age‐related macular degeneration (AMD). Methods: Visual acuity, contrast sensitivity, microperimetry, optical coherence tomography (OCT), and fluorescein (FA) and indocyanine green (ICGA) angiographies of 23 eyes of 23 patients were analysed. Central microperimetry grids with 28 test stimulus sites were automatically aligned with three‐dimensional OCTs and manually aligned with angiographies. Thicknesses of the neuroretina, neuroepithelial detachment (NED), retinal pigment epithelial (RPE) elevation and subretinal tissue were measured under the 644 microperimetry stimulus sites. Areas of classic and occult choroidal neovascularizations (CNVs), subretinal and intraretinal haemorrhage, and late hyperfluorescence in ICGA were identified. The impact of the lesion components on retinal sensitivity was evaluated with correlation analysis and multivariate modelling. Results: Decreased retinal sensitivity correlated significantly with the presence of CNV, haemorrhage, subretinal tissue and RPE elevation. Out of the OCT parameters, the most important determinant of sensitivity was the thickness of RPE elevation (Spearman’s rho, r = ?0.202, p < 0.0001). The thicknesses of subretinal tissue (r = ?0.168, p < 0.0001) and NED had weaker effects (r = ?0.147, p < 0.0001), and the neuroretinal thickness remained nonsignificant. In multivariate modelling, RPE elevation and subretinal tissue in OCT, CNV membranes in angiographies and haemorrhage had the strongest impacts on retinal sensitivity. Conclusion: The most important lesion components affecting retinal function were RPE elevation and subretinal tissue in OCT as well as neovascular membranes and haemorrhage in angiographies. NED and neuroretinal thickening remained less significant.     

雷珠单抗治疗新生血管性年龄相关性黄斑变性的长期疗效

目的：研究就诊于我院新生血管性年龄相关性黄斑变性(NV-AMD)患者使用雷珠单抗治疗后3年的疗效。

方法：回顾性研究。共纳入73例(101眼)患者。根据入组时视力情况(ETDRS chart),患者被分为3组。第1组：视力≤ 35; 第2组：视力36～54; 第3组：视力≥55字母。患者接受3次,每次0.5 mg的雷珠单抗负荷剂量,之后根据病情决定是否再次注射。对患者每月进行一次随访,进行视力、详细的眼前节及眼底的生物显微镜,以及光学相干断层扫描(OCT)检查。对最接近12、24、36mo的视力检查结果进行分析。

结果：纳入的101眼中,男性57眼,女性44眼。患者平均年龄75.1岁。治疗24mo和36mo时,三组患者之间视力变化情况差异均有统计学意义(P=0.002, 0.0001)。治疗36mo后,第2组视力较入组时显著改善(P=0.001),第3组患者视力改善不显著。随访12、24、36mo时,第1组视力无明显变化的患者人数最多。所有患者平均注射雷珠单抗7.3次,随访次数23.9次。

结论：入组时视力情况尚可的患者视力改善最明显。视力较差和视力较好的患者视力改变不明显。最终视力与注射次数无明显关系。     

Increased electroretinogram a‐wave amplitude after intravitreal bevacizumab injection for neovascular age‐related macular degeneration

Purpose: To assess the effect of bevacizumab (Avastin^®), a vascular endothelial growth factor inhibitor, on retinal function by full‐field electroretinography (ERG) in patients with neovascular age‐related macular degeneration (AMD). Design: A prospective, nonrandomized, controlled interventional clinical trial. Methods: Twelve patients (aged 50?85) with neovascular AMD each received one unilateral intravitreal injection of bevacizumab 1.25 mg/0.05 ml as part of the standard management for choroidal neovascular AMD. Before and 1 month after injection, all patients underwent bilateral full‐field ERG scanning by a masked technician according to the ISCEV protocol, and their wave amplitudes were recorded. Untreated eyes served as controls. Scotopic responses were recorded at four incremental light intensities and photopic responses at two incremental light intensities. Changes in ERG‐amplitude responses were calculated. Repeated‐measures anova was used for data analysis. Results: Mean pre‐ and postinjection differences in a‐wave amplitudes between the incremental light intensities in injected eyes were significantly higher than in controls (15.92 versus 1.33 μV for scotopic responses and 4.97 versus ?1.06 μV for photopic responses; p = 0.057 and p = 0.01, respectively). Mean b‐wave amplitudes in injected eyes were significantly higher than in controls for photopic responses (p = 0.048), but for scotopic responses, the difference between treated and untreated eyes was not significant (p = 0.23). Conclusions: Intravitreally injected bevacizumab improves both rod and cone functioning in patients with neovascular AMD, as demonstrated by the increase in the ERG a‐wave responses of these patients. Other measured ERG parameters yielded no significant photoreceptor toxicity.     

Vitreomacular traction and exudative age‐related macular degeneration

Vitreomacular traction resulting from lacking, incomplete or anomalous posterior vitreous detachment is suspected to play a crucial role in the pathogenesis of different forms of age‐related macular degeneration (AMD) along with the known mechanisms. It is probable that the fundamental pathomechanisms of AMD formation have already begun by the time tractional forces lead to a change for the worse. Vitreomacular traction alone is perhaps not able to induce AMD. It would seem sensible to consider vitreous changes when diagnosing and treating AMD patients because of the high coincidence of vitreomacular traction and choroidal neovascularization (CNV) and the often successful treatment of other diseases of the vitreoretinal interface by vitrectomy. The concept of the pathogenesis of AMD should therefore be extended to include the influence of the vitreous, especially where therapeutic concepts such as pharmacological vitreolysis and vitreous separation have been established as causative treatment of late forms of AMD.     

Effect of intravitreal bevacizumab (Avastin®) in neovascular age‐related macular degeneration using a treatment regimen based on optical coherence tomography: 6‐ and 12‐month results

Purpose: To study the effect of intravitreal bevacizumab therapy on visual and anatomical outcomes in patients with neovascular age‐related macular degeneration (AMD) within a follow‐up period of 6 and 12 months. Methods: A retrospective analysis of 102 eyes of 102 consecutive patients with neovascular AMD evaluated repeated intravitreal bevacizumab (1 or 2.5 mg) injections. Retreatment was performed following an optical coherence tomography (OCT)‐based regimen. Ophthalmic examination included best‐corrected visual acuity (BCVA), dilated fundus examination and OCT imaging. Data were analysed at baseline, 6 months (24 weeks) and 12 months (48 weeks) after treatment initiation. Results: BCVA remained stable at 6 months (mean: 0.00 ± 0.41 logMAR; p = 0.95) and 12 months (mean: +0.02 ± 0.43 logMAR; loss of ～ 1 letter; p = 0.70) after the first treatment. OCT retinal thickness decreased by a mean of ?37.8 ± 101.6 μm (p < 0.05) compared to baseline at month 6 and ?38.6 ± 93.3 μm (p < 0.05) at month 12. A mean of 2.6 ± 1.2 injections were needed to obtain absence of fluid by OCT, and the time to recurrence was 23 ± 11 weeks thereafter. There was no difference in BCVA and OCT outcomes between treatment‐naive eyes and eyes that had undergone prior treatment. Conclusion: The 6‐ and 12‐month follow‐up of repeated intravitreal bevacizumab therapy in eyes with neovascular AMD demonstrated stabilization of vision and no safety concerns. An OCT‐based retreatment strategy appears appropriate in the management of patients treated with intravitreal bevacizumab.     

Microperimetric changes in neovascular age-related macular degeneration treated with ranibizumab

Purpose

To assess the value of microperimetry in eyes with neovascular age-related macular degeneration previously treated with ranibizumab and now in the maintenance phase of therapy.

Methods

A total of 21 eyes (14 patients) were included. Microperimetry was performed using the Macular Integrity Assessment Device on at least three occasions for each eye. Intravitreal ranibizumab was administered if visual acuity (VA) or optical coherence tomography (OCT) showed signs of active disease.

Results

Five eyes showed no change in VA or OCT findings, and required no intravitreal injections. In these eyes, mean threshold sensitivity (TS) decreased by 13% (paired t-test, P=0.05) during the study period, but fixation stability (FS) was unchanged. In all, 16 eyes showed signs of disease activity, and therefore required ranibizumab injections during the study. In these eyes, VA, central retinal thickness (CRT), FS, and TS remained unchanged during follow-up. Peak TS was noted when CRT was 210 μm; above or below 210 μm, there was a gradual reduction in TS.

Conclusion

This study has provided novel information on the relationship between macular sensitivity, CRT, and VA in the maintenance phase of ranibizumab therapy. Patients with stable VA and CRT may still have deteriorating retinal sensitivity. This is usually a late manifestation and may indicate subclinical CNV activity.