Automated detection of age-related macular degeneration in color fundus photography: a systematic review

The rising prevalence of age-related eye diseases, particularly age-related macular degeneration, places an ever-increasing burden on health care providers. As new treatments emerge, it is necessary to develop methods for reliably assessing patients' disease status and stratifying risk of progression. The presence of drusen in the retina represents a key early feature in which size, number, and morphology are thought to correlate significantly with the risk of progression to sight-threatening age-related macular degeneration. Manual labeling of drusen on color fundus photographs by a human is labor intensive and is where automatic computerized detection would appreciably aid patient care. We review and evaluate current artificial intelligence methods and developments for the automated detection of drusen in the context of age-related macular degeneration.     

免散瞳数码眼底照相在眼底黄斑部疾病筛查中的应用

目的探讨免散瞳数码眼底照相在眼底黄斑部疾病筛查中的应用。方法应用免散瞳数码眼底照相对3742人(7484眼)50岁以上人群进行眼病筛查,对筛查出的黄斑部疾病或可疑疾病者进行光学相干断层成像扫描检查,分析两种检查诊断结果的一致率。结果除去眼底照相结果黄斑区未照出145人(201眼)及黄斑不清晰者683人(984眼),余2914人(6299眼)中筛出黄斑部疾病或可疑疾病266例(354眼),其中黄斑前膜38例44眼),黄斑裂孔35例(39眼),黄斑变性193例(271眼),经与光学相干断层成像扫描对比,两种检查方法诊断结果的总一致率为75.94%。结论免散瞳数码眼底照相在黄斑部疾病的诊断中具有较高的准确性,可作为眼底黄斑部疾病筛查的首选方法。     

Screening for age-related macular degeneration using nonstereo digital fundus photographs

Age-related macular degeneration (AMD) is a disease with significant visual morbidity and accounts for the majority of blind registrations in the developed world including the UK. Certain forms of neovascular AMD are amenable to treatment but require expeditious referral to a retinal specialist. AIM: To evaluate the possibility of using nonstereo fundus photographs as a low-cost screening tool for neovascular AMD. DESIGN: Retrospective review of patients referred to the macular clinic of a teaching hospital in London. METHODS: A total of 198 randomised digital fundus photographs, without any other clinical information, were presented to two independent ophthalmic interns who graded them into one of the three categories: normal, age-related maculopathy (ARM), or neovascular age-related macular degeneration (AMD) to determine the urgency of referral to clinic. The results were compared with the known diagnosis for each patient and sensitivities and specificities for each diagnostic category calculated. RESULTS: The intraobserver Kappa statistic was 0.75 and 0.91 for grader 1 and 2, respectively. The interobserver Kappa was 0.54. The mean sensitivity and specificity for the identification of ARM was 60.5 and 76.3%, respectively The mean sensitivity and specificity for the identification of AMD was 85.7 and 78.8%, respectively. CONCLUSION: Nonstereo digital fundus photograph is a reasonable screening tool for CNV and may aid in decreasing the visual morbidity it causes by enabling timely referrals and treatment.     

Topical fundus pulsation measurements in age-related macular degeneration

Background: The purpose of the present study was to investigate regional fundus pulsations in age-related macular degeneration (AMD) patients with subretinal neovascular membranes. • Methods: Local fundus pulsation amplitudes (FPAs) were measured in 12 patients with AMD with classic neovascular membranes. Measurements were performed directly on the membrane and adjacent to the membrane. FPAs were assessed with a recently developed laser interferometric method. FPA measurements were performed in 12 healthy subjects at similar posterior pole locations. • Results: In AMD patients FPAs were consistently lower when measured directly on the neovascular membrane (“inside”) than at measurement sites around the membrane (“outside”). The difference in FPA was 26 ± 3% (mean ± SEM, range 13–40%, P < 0.0001). In healthy subjects, however, FPAs were significantly higher at the measurement points corresponding to “inside” points (15 ± 4%, P < 0.0006). • Conclusions: We have shown that FPAs are reduced at classic neovascular membranes in patients with AMD. The mechanism behind this finding remains unclear. Hence, future studies have to ascertain whether this observation is associated with changes in fundus layers or with local choroidal perfusion abnormalities. Received: 17 February 1997 Revised version received: 29 April 1997 Accepted: 26 May 1997     

Evaluation of fundus autofluorescence patterns in age-related macular degeneration

AIM: To study the various morphological patterns of fundus autofluorescence (FAF) images in patients with age-related macular degeneration (AMD) in Indian population. METHODS: Totally 179 eyes of 104 patients with clinical diagnosis of AMD were recruited into the study. Autofluorescence images were captured using confocal scanning laser ophthalmoscope and the patterns of FAF were classified. RESULTS: Of 179 eyes, 27 (15.08%) were early AMD, 58 (32.41%) were intermediate AMD, 94 eyes (52.51%) were late AMD. Of 94 eyes with late AMD, 79 (84.04%) were neovascular AMD and 15 (15.96%) were central geographic atrophy. In eyes with early and intermediate AMD, 9 patterns of FAF were noted. Six patterns (normal, minimal change, focal increased, patchy increased, linear, reticular) were similar to that in the published classification. Two patterns (lacelike and speckled) described in the published classification were not found. Three new patterns (focal hypo-fluorescence, patchy hypo-fluorescence, mixed focal hypo-fluorescence and hyper-fluorescence) were detected. In eyes with neovascular AMD, 6 morphological patterns of FAF were noted. Two patterns (mixed hypo-fluorescence and hyper-fluorescence, central hypo-fluorescence with hyper-fluorescent rim) were similar to that in published classification. Two patterns (normal, near normal or normal background fluorescence in the centre of hypo-fluorescent area) described in the published classification were not found. Four new patterns (minimal change, hypo-fluorescent patch, central hypo-fluorescence with surrounding reticular, bull’s eye) were recognized. In eye with central geographic atrophy 5 morphological patterns were noted and these were similar to that in published classification. CONCLUSION: Phenotypic differences in the pattern of FAF exist in the study population compared to existing classification systems.     

An evaluation of photographic screening for neovascular age-related macular degeneration

BACKGROUND: Photographic screening for neovascular age-related macular degeneration (AMD) is not commonly employed because the prevalence of treatable disease is low and fluorescein angiography is considered necessary for the diagnosis of this form of AMD. However, there may be a role for colour retinal imaging in assisting with the diagnosis and triage of subjects with neovascular AMD. The purpose of this study was to evaluate the utility of colour fundus photographs for identifying subjects with potentially treatable neovascular AMD. METHODS: A total of 74 stereo pairs of Kodachrome colour slides of subjects with AMD were evaluated (i) nonstereoscopically, (ii) stereoscopically, and (iii) stereoscopically with visual acuity and visual symptom data. Two retina specialists read the images to identify active exudative lesions. RESULTS: The kappa statistic comparing the retinal specialists diagnosis of treatable neovascular AMD from color slides was excellent. The sensitivity and specificity of nonstereo images for the appropriate categorization of lesions was 0.95 and 0.90 respectively. The evaluation of stereo pairs was more sensitive, but less specific, 0.98, 0.83, as was the evaluation of stereo-pairs with clinical histories and visual acuities, 1.00, 0.77. CONCLUSIONS: The evaluation of colour images for subjects with suspected exudative macular degeneration can be diagnostic for neovascular AMD and may expedite the appropriate referral of patients for more timely angiography and treatment. Incorporating more clinical information for the image evaluators ((i) stereo image pairs and/or (ii) presenting symptomatology and visual acuity data) led to a decrease in the false-negative rate, but also decreased the screening specificity.     

糖尿病视网膜病变的数码眼底照相筛查方法评价

目的 评估单视野和多个视野数码彩色眼底照相方法筛查早期糖尿病视网膜病变(DR)的价值.设计 前瞻性临床病例系列.研究对象 连续选择北京同仁医院糖尿病科门诊确诊的非增殖性糖尿病视网膜病变的糖尿病患者108例.方法所有病例均充分散瞳,分别进行单视野、双视野和6视野数码彩色眼底照相和荧光素眼底血管造影(FFA)检查.眼底病专科医师阅片进行诊断,以FFA诊断为标准.主要指标 各种视野眼底照相方法进行筛查诊断的敏感性、特异性及与FFA诊断结果的一致性.结果 以DRI期为筛查阈值时,单视野眼底彩色照相的敏感度、特异度、Kappa值分别为73.21%、88.64%、0.46;双视野眼底照相分别为75.00%、86.36%、0.47;6视野眼底照相分别为76.05%、87.80%、0.48.以DR2期为筛查阈值时,单视野眼底彩色照相的敏感度、特异度、Kappa值分别为72.46%、93.01%、0.68;双视野眼底照相分别为73.91%、93.01%、0.69;6视野眼底照相分别为75.36%、92.81%、0.70.单视野与6视野眼底照相诊断结果一致性Kappa值为0.97.结论 黄斑为中心单视野45°眼底照相可作为早期尤其是DR2期以上糖尿病视网膜病变的筛查方法.     

Image enhancement of color fundus photographs for age-related macular degeneration: the Shanghai Changfeng Study

AIM:To develop and evaluate a new fundus image optimization software based on red,green,blue channels(RGB) for the evaluation of age-related macular degeneration(AMD) in the Chinese population.METHODS:Fundus images that were diagnosed as AMD from the Shanghai Changfeng Study database were analyzed to develop a standardized optimization procedure.Image brightness,contrast,and color balance were measured.Differences between central lesion area and normal retinal area under different image brightness,contrast,and color balance were observed.The optimal optimization parameters were determined based on the visual system to avoid image distortion.A paired-sample diagnostic test was used to evaluate the enhancement software.Fundus optical coherence tomography(OCT) was used as the gold standard.Diagnostic performances were compared between original images and optimized images using Mc Nemar’s test.RESULTS:A fundus image optimization procedure was developed using 86 fundus images of 74 subjects diagnosed with AMD.By observing gray-scale images,choroid can be best displayed in red channel and retina in green channel was found.There was limited information in blue channel.Totally 104 participants were included in the paired sample diagnostic test to assess the performance of the optimization software.After the image enhancement,sensitivity increased from 74% to 88%(P=0.008),specificity decreased slightly from 88% to 84%(P=0.500),and Youden index increased by 0.11.CONCLUSION:The standardized image optimization software increases diagnostic sensitivity and may help ophthalmologists in AMD diagnosis and screening.     

Focal electroretinograms and fundus appearance in nonexudative age-related macular degeneration

· Background: The aim of this study was to evaluate the focal electroretinogram (FERG), an objective indicator of outer retinal function, in nonexudative age-related macular degeneration (NE-AMD), and to compare FERG results with morphological lesions assessed by stereoscopic fundus photographs and fluorescein angiograms. · Methods: Twenty-five patients (25 eyes) with bilateral NE-AMD (visual acuity of the study eyes ≥0.4) as well as 10 age- and sex-matched control subjects (10 eyes) were evaluated. FERGs were recorded from the macular region (9°) in response to sinusoidal stimuli flickered at 32 Hz. Amplitude and phase angle of the Fourier-analyzed FERG fundamental component were measured. Fundus lesions were graded from color slides according to the Wisconsin age-related maculopathy grading system [15]. Fluorescein angiograms were evaluated by an image analysis technique to compute the area with pathological hyperfluorescence (associated with drusen and/or retinal pigment epithelial atrophy) within the macular (approximately 9°×9°) region. · Results: Compared to control eyes, NE-AMD eyes had a reduction in the mean FERG amplitude (57% loss, P<0.001) with no phase changes. Amplitudes of individual affected eyes were negatively correlated with either the Wisconsin grading score (r=–0.63, P<0.001) or the percentage area of pathological hyperfluorescence (r=–0.70, P<0.01). Eyes with minimal NE-AMD lesions (Wisconsin score ≤6) and normal acuity had a lower mean amplitude (47% loss, P<0.05) than that of control eyes. · Conclusions: The results indicate that, in NE-AMD, the FERG is altered in parallel with the extent and severity of fundus lesions. However, a functional impairment of outer macular layers, which is detected by FERG losses, could precede morphological changes typical of more advanced disease. Received: 6 March 1998 Revised version received: 5 June 1998 Accepted: 17 June 1998     

Novel automated screening of age-related macular degeneration

Purpose

To determine the objective and quantitative hyperspectral parameters for distinguishing between age-related macular degeneration (AMD) and a normal macula.

Methods

Near-infrared hyperspectral images were taken of 71 eyes of 62 AMD patients with exudative AMD and 21 eyes of 12 control subjects without AMD. The spatial information included a 480?×?321-pixel image in a 50° field located at the ocular fundus and a 720–950-nm-per-pixel reflectance spectrum. Macular vectors were determined as the average spectrum for each macula, and reference vectors were used as average macular vectors for healthy volunteers. Variations in vector length and angle were calculated based on comparison with the reference vector. The AMD differentiation index was a parameter that minimized the plot overlap between AMD patients and controls.

Results

Statistically significant differences between the AMD patients and controls were noted. Receiver-operating characteristic curve analysis revealed an area under the curve of 0.888. The appropriate threshold values were attained for the proposed discrimination index, including 68?% sensitivity, 95?% specificity and 74?% accuracy.

Conclusions

This study presents a simplified diagnostic index for the determination of age-related macular degeneration based on near-infrared spectra.     

老年性黄斑变性的吲哚青绿和荧光素眼底血管造影

目的 探讨眼底荧光素血管造影(fundus fluorescein angiography,FFA)和吲哚青绿血管造影(indocyanine green angiography,ICGA)在老年性黄斑变性(age-related macular degeneration,AMD)患者中的临床应用.方法 对AMD患者375例742只眼的FFA和ICGA检查资料进行分析总结.结果 在所有患者中,萎缩型504只眼(67.9%),渗出型238只眼(32.1%).在同步进行FFA和ICGA检查的渗出型AMD93只眼中,FFA检查发现典型性CNV 14只眼(15.1%),隐匿性CNV 79只眼(84.9%);ICGA检查发现边界清楚的CNV48只眼(51.6%),两者相比差异具有统计学意义(x2=27.97,P＜0.01).ICGA检查发现CNV的供养血管6只眼(6.5%),均位于中心凹旁或中心凹外.在发现边界清楚CNV的48只眼中,中心凹下CNV29只眼(60.4%),中心凹旁CNV 12只眼(25.0%),中心凹外CNV7只眼(14.6%).结论 与FFA相比,ICGA可以更加准确地显示CNV,发现CNV的供养血管,对AMD的临床诊断和治疗具有更重要的指导意义.     

Multimodal evaluation of macular function in age-related macular degeneration

Objective

To evaluate macular function using multimodality in eyes with age-related macular degeneration (AMD) at various stages.

Methods

Macular function in 20 control eyes (20 subjects), 17 eyes (17 patients) with large drusen, 18 eyes (18 patients) with drusenoid pigment epithelial detachment (PED), and 19 eyes (19 patients) with neovascular AMD was examined using a Landolt chart for visual acuity; retinal sensitivity was measured by microperimetry; and focal macular electroretinography (fmERG) was performed. In all of these eyes, retinal morphology was examined using optical coherence tomography.

Results

Eyes with neovascular AMD showed morphologic changes in the neurosensory retina as well as marked deterioration of macular function in all parameters measured with a Landolt chart, fmERG, and microperimetry. Eyes with large drusen showed only minimal morphologic changes in the neurosensory retina. In this large drusen group, although retinal sensitivity at the central point was significantly decreased (P = 0.0063), the other parameters of macular function were well preserved. In eyes with drusenoid PED, the structure of the neurosensory retina was well preserved, while the foveal thickness was significantly increased (P = 0.013). The macular function of these eyes was significantly deteriorated, with the VA, amplitude of the a-wave and b-wave, and retinal sensitivity being markedly decreased. In addition, the area of PED correlated with the latency of the a-wave and b-wave and with the retinal sensitivity within the central 4° or 8° region.

Conclusion

Multimodal evaluation demonstrated a significant decrease in macular function in drusenoid PED and in neovascular AMD.     

Feasibility of screening for high-risk age-related macular degeneration with an Internet-based automated fundus camera.

BACKGROUND AND OBJECTIVE: The objective of this pilot study was to determine whether a new screening system, the DigiScope (EyeTel Imaging, Inc., Columbia, MD), can detect the presence of age-related macular degeneration (AMD) at a level requiring referral to an ophthalmologist for further evaluation and possible treatment. PATIENTS AND METHODS: The DigiScope is an Internet-based semi-automated digital imaging system designed to be in primary care physicians' offices. Forty-two eyes of 21 patients with different categories of AMD were imaged with both the DigiScope and a standard color fundus camera. The imaging capability of the two modalities was compared for identification of lesions associated with AMD and classification into stages. RESULTS: There was good agreement for low-risk lesions and excellent agreement for high-risk lesions. Thirty-five of 36 eyes with intermediate or advanced disease were correctly identified with DigiScope images. Choroidal neovascularization was identified in all cases with the DigiScope due to the presence of subretinal hemorrhage or subretinal fibrosis. The DigiScope was found less capable of detecting subretinal fluid than standard stereo fundus photographs. CONCLUSIONS: This pilot study suggests that the DigiScope may be a useful screening tool for AMD.     

眼底自发荧光技术在湿性年龄相关性黄斑变性诊断中的应用

湿性年龄相关性黄斑变性是年龄相关性黄斑变性的晚期阶段,可导致80％以上患者重度视力丧失,目前临床上诊断主要依靠相干光断层扫描和荧光素眼底血管造影等形态学检查手段,而眼底自发荧光(fundus autofluorescence,FAF)成像技术作为一种非侵入性检测手段,能反应脂褐质的分布及视网膜色素上皮层的活性,已逐渐成为湿性年龄相关性黄斑变性诊治中的观测指标之一.     

萎缩性黄斑变性的眼底自发荧光特征

背景年龄相关性黄斑变性（AMD）的早期诊断和治疗至关重要。以往对AMD的诊断主要参照荧光素眼底血管造影（FFA）和光学相干断层扫描（OCT）,但眼底自发荧光技术（FAF）无需注射造影剂,大大优化了诊断过程。目的观察萎缩性AMD的FAF特征。方法28例39眼萎缩性AMD按照陈松的分类方法进行分组,应用激光共焦扫描检眼镜HRA2获得所有患者的FAF平均图像,并与眼底照相或FFA结果进行比较。结果萎缩性AMD的FAF信号异常增高或降低区域与眼底的改变可能对应或不对应。萎缩性AMD萎缩前期FAF改变包括轻微改变、局灶性、片状、线性、花边样、网状和斑点状增强等7种形态。萎缩性AMD萎缩期地图状萎缩区呈边界清晰的低FAF区,其交界区表现为正常FAF、FAF带状增强或弥漫性增强;非地图状萎缩呈边界不清的低FAF区,其交界区FAF弥漫性增强。结论FAF成像技术为萎缩性AMD的诊断提供了一种新的非侵入性检查手段。     

Analysis of digital scanning laser ophthalmoscopy fundus autofluorescence images of geographic atrophy in advanced age-related macular degeneration

BACKGROUND: Fundus autofluorescence (AF) imaging using confocal scanning laser ophthalmoscopy (cSLO) has been shown to be superior to fundus photography or angiography for delineating areas of geographic atrophy (GA) in retinal pigment epithelium (RPE) and for recording variation over time. We have evaluated a method for automated computerized detection and quantitation of RPE atrophy. METHODS: AF images in vivo were recorded with a confocal scanning laser ophthalmoscope (exc. 488 nm, em. >500 nm; Heidelberg Retina Angiograph). The intensity of AF in atrophic areas was markedly decreased. Two independent readers analysed these areas in 24 right eyes manually by outlining GA areas using a mouse-driven arrow (method A) and automatically by image analysis software (Global Lab Image/2) after subjective adjustment of thresholding (method B). Agreement between observers and between methods A and B was assessed by the Bland-Altman design for method-comparison studies. RESULTS: Larger areas were measured using method A than B by both readers (agreement A/B: reader 1 mean difference 1.04 mm, 95% CI [0.66,1.42]; reader 2 mean difference 0.62 mm, 95% CI [0.43,0.81]). The agreement between the readers was mean difference 0.39 mm (95% CI [0.02,0.76]) for A and mean difference -0.03 mm (95% CI [-0.23,0.18]) for B. Features making the delineation of borders of GA difficult included large choroidal vessels with autofluorescent properties in the GA area and media opacities. CONCLUSIONS: Fundus AF cSLO imaging provides a reliable means to delineate areas of GA. The automated image analysis allows more accurate detection and quantitative documentation of atrophic areas than manual outlining. This method will be useful in longitudinal natural history studies and for monitoring effects of future therapeutic interventions to slow down GA progression in patients with advanced atrophic ARMD and other retinal diseases associated with outer retinal atrophy.