Three‐year results of visual outcome with disease activity–guided ranibizumab algorithm for the treatment of exudative age‐related macular degeneration

Purpose: To evaluate 3‐year follow‐up treatment outcomes with ranibizumab (Lucentis^®) 0.5 mg administered either monthly or quarterly on a pro re nata (PRN) basis according to a disease activity–guided monitoring and treatment algorithm. Methods: A total of 316 treatment‐naive eyes of 316 patients with exudative age‐related macular degeneration met the criteria for inclusion in this retrospective, interventional case series. Patients were treated with ranibizumab 0.5 mg according to a disease activity–guided algorithm with monthly monitoring. Optical coherence tomography and fluorescein angiography were routinely used to assess disease activity: active lesions were treated with a series of three monthly injections, whereas inactive lesions were treated with quarterly injections. Results: Mean Early Treatment Diabetic Retinopathy Study best‐corrected visual acuity improved from 52 letters at baseline to 59 letters at 12 months, achieved with a mean of 7.1 injections, 61 letters at 24 months with a mean of 5.0 injections administered in the second year and 60 letters at 36 months with a mean number of 5.2 injections. Conclusions: Monthly visits and a morphology‐driven PRN regimen with 3 injections in case of recurrence plus quarterly injections in case of inactive CNV resulted in an average VA gain of 7–9 letters that could be maintained over 3 years.     

Multimodal imaging of dry age‐related macular degeneration

Purpose: The purpose of this study was to understand clinical significance of near‐infrared reflectance (NIR), blue fundus autofluorescence (FAF) and near‐infrared autofluorescence (NIA) in dry age‐related macular degeneration (AMD), by correlation with fluorescein angiography (FA) and cross‐sectional spectral domain optical coherence tomography (SD OCT). Methods: We evaluated 110 eyes (62 patients, mean age: 64 ± 8 years) diagnosed with dry AMD between January 2010 and December 2010, which underwent NIR (λ = 830 nm), FAF and FA (excitation λ = 488 nm; emission λ > 500 nm), NIA (excitation λ = 787 nm; emission λ > 800 nm), and simultaneous SD OCT scanning using a combined confocal scanning laser ophthalmoscope/SD OCT device (Spectralis HRA + OCT; Heidelberg Engineering, Heidelberg, Germany). Results: Drusen showed variable increased/decreased NIR, FAF, NIA and FA, which corresponded to variable increased/decreased thickness of the retinal pigment epithelium (RPE) and possible presence of subretinal deposits on SD OCT. Geographic atrophy (GA) was present in 43/110 eyes (39.0%) and showed increased NIR and fluorescence (FA), absent FAF and NIA, and loss of RPE on SD OCT. The hyperautofluorescence of the GA margin was never larger in FAF than that in NIA, while in 16.2% of cases, it was larger in NIA than that in FAF and corresponded to mild choroidal hyperreflectivity on SD OCT. Conclusions: Simultaneous recording of SD OCT scans provided ultrastructural data for the evaluation of NIR, FAF, NIA and FA in dry AMD. Near‐infrared autofluorescence might detect earlier than FAF areas of RPE cell loss at the GA margin.     

Intrasession repeatability of optical coherence tomography measures in active neovascular age‐related macular degeneration

Objectives: To determine the repeatability of Stratus optical coherence tomography fast macular thickness map analysis in patients with active neovascular age‐related macular degeneration (nAMD). Methods: Consecutive pairs of scans from 112 eyes of 112 consecutive patients with active nAMD were analyzed. The Bland–Altman coefficient of repeatability (CR) was calculated for each retinal thickness or volume measure. Results: The CR for the central 1 mm macular subfield was 59 μm (18% of retinal thickness) and did not exceed 69 μm in any subfield. There was much poorer repeatability for the center‐point thickness (CPT) measure (CR of 78 μm; 24%). However, in the subgroup of 38 patients with no Stratus software low analysis confidence message on either analysis map, the revised CR (42 μm) for the CPT measure and the A1 subfield (40 μm) were similar. Conclusion: Optical coherence tomography‐derived retinal thickness measurements are subject to measurement variability in patients with active nAMD. The results suggest a change criterion of more than 59 μm in central 1 mm (A1) subfield macular thickness is necessary to distinguish true clinical change from measurement variability in these patients.     

Combined intravitreal bevacizumab and triamcinolone in exudative age‐related macular degeneration

Acta Ophthalmol. 2010: 88: 630–634

Abstract.

Purpose: We report on the combined application of intravitreal bevacizumab and triamcinolone acetonide for treatment of exudative age‐related macular degeneration (AMD). Methods: The clinical interventional case‐series study included 16 patients (16 eyes) with exudative AMD who had previously received 3.5 ± 1.8 mono‐injections of bevacizumab (1.5 mg) without significant improvement in visual acuity (VA) or reduction in macular exudation. All patients underwent a combined intravitreal injection of bevacizumab (1.5 mg) and triamcinolone acetonide (about 20 mg). Main outcome measures were VA and macular thickness as determined by optical coherence tomography. All patients were re‐examined at 2–3 months after the intervention. Results: Visual acuity improved significantly (p = 0.03) from 0.80 ± 0.40 logMAR prior to the combined injection to 0.65 ± 0.42 logMAR at 3 months after the injection. An improvement of ≥ 1 Snellen line was found in eight subjects, an increase of ≥ 2 lines in five subjects, and an improvement of ≥ 3 lines in two subjects. One patient lost 1 line and one patient lost 3 lines. Central retinal thickness decreased significantly from 272 ± 62 μm to 220 ± 47 μm (p = 0.03). At the 6‐month follow‐up examination, central retinal thickness had increased again to 319 ± 142 μm, which was not significantly (p = 0.30) different from baseline measurements. Conclusions: The combined intravitreal application of bevacizumab and triamcinolone may temporarily be helpful in the treatment of exudative AMD if previous intravitreal bevacizumab mono‐injections have failed to improve vision and reduce macular oedema.     

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.     

光动力疗法治疗渗出性年龄相关性黄斑变性

目的观察光动力疗法(photodynamic therapy,PDT)治疗渗出性年龄相关性黄斑变性(age-related macular degeneration,AMD)的疗效。方法回顾分析经荧光素眼底血管造影(fundus fluorescein angiography,FFA)、吲哚菁绿血管造影(indocyanine green angiography,ICGA)以及光学相干断层扫描(optical coherence tomography,OCT)检查确诊的21例(31眼)渗出性AMD患者PDT治疗前及治疗后的临床资料,主要以视力、FFA及(或)ICGA、OCT的改变为观察指标,评价PDT对渗出性AMD的治疗效果。结果治疗后13眼视力明显改善(视力提高≥2行),占41.9%;14眼视力稳定不变(视力波动在1行以内),占45.2%;4眼视力下降2行,占12.9%。大部分患眼于PDT治疗后眼底出血和渗出减轻;ICGA检查显示:PDT治疗后1周,16眼CNV的渗漏明显减少或完全停止,8眼渗漏完全停止。OCT检查显示:CNV周围视网膜脉络膜水肿以及神经上皮脱离好转。5例6眼患者在PDT治疗过程中及治疗后发生视网膜神经上皮脱离范围变大,1例1眼发生黄斑部再次大面积出血,所有病例均未发生任何全身不良反应。结论单次和重复PDT治疗可以部分或完全封闭渗出性AMD的CNV,PDT治疗对病灶周围的正常视网膜和脉络膜组织短期内有轻度影响,对视力无损害。     

Relationship between macular pigment and visual acuity in eyes with early age‐related macular degeneration

Purpose: Today the extent to which MP impacts visual function in early AMD remains unclear. This study examines the relationship between macular pigment optical density (MPOD) and high‐contrast visual acuity (HC‐VA) and low‐contrast visual acuity (LC‐VA) in eyes with early age‐related macular degeneration (AMD). Methods: Measurements were made in 22 subjects with early AMD and 27 healthy control subjects. Distance best‐corrected VA was measured using HC (96%) and LC (10%) Bailey‐Lovie logMAR letter charts under photopic luminance conditions. MPOD was determined at the fovea through apparent motion photometry using the cathode ray tube‐based Metropsis psychophysical vision test (Cambridge Research Systems). Results: No significant differences in foveal MPOD were detected between the control eyes (0.30 ± 0.24 log units) and eyes with early AMD (0.27 ± 0.15 log units). Neither were differences detected between the two groups in mean HC‐ and LC‐VA. Foveal MPOD showed significant correlation with both photopic HC‐VA (r = ?0.47, p = 0.0008) and LC‐VA (r = ?0.46, p = 0.0008) such that as MPOD increased, photopic HC‐VA and LC‐VA improved (lower logMAR values). Conclusions: Low MP levels were related to worse visual function in both healthy eyes and eyes with early AMD. Our findings provide direction for future studies designed to improve retinal function through the use of oral supplements known to increase MP levels, especially in eyes with AMD and a low MPOD.     

Reproducibility of retinal thickness measurements in patients with age‐related macular degeneration using 3D Fourier‐domain optical coherence tomography (OCT) (Topcon 3D‐OCT 1000)

Purpose: Conventional time‐domain optical coherence tomography (OCT) has become an important tool for following dry or exudative age‐related macular degeneration (AMD). Fourier‐domain three‐dimensional (3D) OCT was recently introduced. This study tested the reproducibility of 3D‐OCT retinal thickness measurements in patients with dry and exudative AMD. Methods: Ten eyes with dry AMD and 12 eyes with exudative AMD were included in the study. Sets of three OCT 6 × 6‐mm raster scans were taken by one operator. Mean retinal thickness was calculated for 36 areas. Coefficients of variation (CoV) were calculated for each patient and area. For analysis, two separate areas (central and peripheral) were defined. Generalized estimating equations (GEEs) were applied to all 36 subfields in order to analyse possible differences in CoV and mean retinal thickness between dry and exudative AMD. Results: Mean retinal thickness values were significantly larger in the central area in exudative AMD (p < 0.001). Mean CoV for exudative AMD was 3.7% (standard deviation [SD] 1.4%). Mean CoV for dry AMD was 1.8 (SD 0.6%). The reproducibility of retinal thickness measurements was significantly less in exudative AMD (p = 0.009). Conclusions: Reproducibility of 3D‐OCT retinal thickness measurements was good in both groups. However, reproducibility was significantly better in dry AMD than in exudative AMD.     

Cytokine concentration in aqueous humour of eyes with exudative age‐related macular degeneration

Purpose: To measure the concentration of cytokines in the aqueous humour of eyes with exudative age‐related macular degeneration (AMD). Methods: The clinical interventional study included a study group of 18 patients with exudative AMD and a control group of 20 patients undergoing routine cataract surgery. Age did not vary significantly (p = 0.36) between study group (80.8 ± 6.4 years) and control group (77.0 ± 9.9 years), nor did gender (p = 0.75). During the interventions, aqueous humour samples were obtained, in which the concentration of cytokines was measured using a solid‐phase chemiluminescence immunoassay. Macular thickness was measured by optical coherence tomography (OCT). Results: In the study group as compared to the control group, significantly higher concentrations were measured for epithelial growth factor (EGF) (p = 0.017), human growth factor (HGF) (p = 0.048), intercellular adhesion molecule‐1 (ICAM1) (p = 0.028), interleukin 12p40 (IL12p40) (p = 0.009), interleukin 1a2 (IL1a2) (p = 0.01), interleukin 3 (IL3) (p = 0.02), interleukin 6 (IL6) (p = 0.006), interleukin 8 (IL8) (p = 0.02), monocyte chemoattractant protein‐1 (MCP‐1) (p = 0.048), monokine induced by interferon gamma (MIG) (p = 0.016), matrix metalloproteinase 9 (MMP9) (p = 0.004) and plasminogen activator inhibitor 1 (PAI1) (p = 0.006). Macular thickness was significantly associated with the concentrations of EGF (p = 0.001), HGF (p = 0.02), ICAM1 (p = 0.001), interleukin 12p40 (p = 0.006), IL 1a2 (p = 0.002), MIG (p = 0.001), MMP9 (p < 0.001) and PAI1 (p = 0.01). Interleukin 6 and MCP‐1 showed significant associations with the height of retinal pigment epithelium detachment. Conclusions: Numerous cytokines are associated with the presence and the amount of exudative AMD.     

Intravitreal bevacizumab (Avastin®) for neovascular age‐related macular degeneration in treatment‐naive patients

Purpose: To report the effects of intravitreal bevacizumab (Avastin^®) in treatment‐naive patients with exudative age‐related macular degeneration (ARMD) assessed by visual acuity (VA), optical coherence tomography (OCT) and contrast sensitivity. Methods: A prospective, uncontrolled, pilot study of 26 eyes of 26 patients, all previously treatment‐naive to photodynamic therapy, argon laser or anti‐vascular endothelial growth factor (VEGF), were treated with one or more intravitreal injections of 1.25 mg bevacizumab. Of the 26 patients, 15 (57.7%) had occult choroidal neovascularization (CNV), 6 (23.1%) had predominantly classic CNV and 5 (19.2%) had minimally classic CNV. Ophthalmic outcome measures included changes in standardized Early Treatment Diabetic Research Study (ETDRS) VA, contrast sensitivity and OCT. The patients were examined at baseline and 1 week, 6 weeks, 3 months and 6 months after the first injection. Re‐treatment was given on an ‘as needed’ basis. Results: Twenty‐four eyes of 24 patients completed 6 months of follow‐up. Two patients chose to discontinue the study. Mean ETDRS VA score improved from 55 letters at baseline to 60 letters at 1 week (P < 0.01) and to 61 letters at 6 weeks (P < 0.01). No significant improvement in VA from baseline was found after 3 and 6 months. Patients with pigment epithelial detachment (PED) had a significantly worse outcome in VA at 6 months. Contrast sensitivity improved from baseline to 3 or 6 months, but this improvement was not statistically significant. Mean macular thickness decreased significantly from baseline to all follow‐up examinations (P < 0.01). Conclusion: Mean ETDRS VA improved significantly after 1 and 6 weeks; thereafter, it remained stable throughout the study period. Macular thickness improved significantly at all time points. The results indicate that 1.25 mg intravitreal bevacizumab is associated with functional as well as morphological improvement among treatment‐naive ARMD patients.     

Sub‐retinal neovascular membrane in exudative macular degeneration

Age‐related macular degeneration is a major cause of serious vision loss. The earliest stages of age‐related maculopathy may be defined by the size of the drusen present in the macula and the effects on vision. Further manifestations may include soft drusen, choroidal neovascularisation, macular haemorrhage and cicatricial or disciform degeneration of the macula. This report describes a patient with a macular haemorrhage, a choroidal neovascular membrane and serious loss of vision. In addition, the pathogenesis, diagnosis and treat‐ment options of macular degeneration are reviewed.     

Illumination and reading performance in age‐related macular degeneration

Background: Previous studies have compared low vision reading performance at optimal task illuminance and consulting room illuminance (500 to 600 lux). However, it is uncertain the extent to which low vision reading performance can be improved when task illumination is increased from levels more representative of those found in the typical living room (50 lux) to levels likely to maximise performance. Methods: Reading performance of 20 subjects with age‐related macular degeneration (AMD) was assessed for a range of print sizes using sentence reading charts at six levels of task illuminance (50 to 5,000 lux). Subjects read without low vision devices. Results: Sentence reading acuity and critical print size improved by a factor of two over the 50 to 5,000 lux range, while maximum reading rate improved by a factor of 1.4. For the majority of subjects (70 per cent), the optimal task illuminance (determined objectively) was higher (median 3,500 lux) than the subjectively preferred task illuminance (median 2,450 lux). Reading performance was significantly better at the optimal illuminance than at illuminances equivalent to those found in the domestic environment (50 lux) or consulting room (600 lux). Conclusions: The majority of AMD patients will require task illumination of at least 2,000 lux to maximise reading performance. Optimal illumination should be determined individually for each patient using both objective measures of performance, such as reading acuity, and subjective assessments of visual comfort.     

Outer retinal cysts in age‐related macular degeneration

Purpose: To describe novel cystic structures (‘outer retinal cysts’ or ORC) found in the outer retina in age‐related macular degeneration (AMD). Methods: One hundred and seventy‐three consecutive eyes of 88 AMD patients were prospectively examined with spectral domain optical coherence tomography (SD‐OCT). The prevalence of ORCs was searched, and their sizes and shapes were determined. Results: SD‐OCT revealed round or ovoid, intraretinal, hyporeflective cystic structures with a hyperreflective border in 60 eyes (56%) with neovascular AMD and in six eyes (21%) with atrophic AMD. These cystic structures were of different sizes and shapes. They remained stable in all the patients after a follow‐up period of 6 months. Conclusions: Outer retinal cyst is a new type of cystic structure recently identified in AMD patients. ORCs should not be confused with intraretinal exudates or cystoid cavities and therefore do not require any treatment. The histopathological nature of ORC remains to be determined. Further studies are necessary to determine their true origin.