年龄相关性黄斑变性患者眼底玻璃膜疣的自发荧光特征

目的 探讨非渗出性年龄相关性黄斑变性(AMD)患者眼底玻璃膜疣的自发荧光特征.方法 回顾性病例系列研究.对明确诊断的63例(78只眼)非渗出性AMD患者的临床资料进行回顾性分析.所有患者均采用海德堡共焦激光眼底扫描仪(HRA2-cSLO)拍摄眼底玻璃膜疣自发荧光图像,同时与Kowa Nonmyd 7型眼底照相机和频域相干光断层扫描仪(OCT)拍摄的眼底彩色照片和三维OCT图像进行对比观察,分析AMD患者眼底玻璃膜疣自发荧光特征.结果 63例(78只眼)非渗出性AMD患者眼底玻璃膜疣的自发荧光图像并不与眼底彩色照片和频域OCT图像显示的玻璃膜疣病灶完全吻合.78只眼中,仅有68只眼显示异常自发荧光,根据这些异常自发荧光的形态特点可将其分为7种类型,即微小病变型、局部融合型、线条型、斑片型、花边型、斑驳型及散在不均一型;其余10只眼在彩色眼底照片上显示很小的点状或簇状玻璃膜疣,但用HRA2-cSLO拍摄其眼底荧光图像时并未显示异常自发荧光,而表现为均匀一致型似正常眼底的自发荧光.此外,15例患者的双眼均出现异常自发荧光,且其中13例双眼的自发荧光类型不对称,说明患者双眼的眼底病变程度和范围不对称.结论 HRA2-cSLO可清晰拍摄非渗出性AMD患者眼底玻璃膜疣的异常自发荧光图像,形态各异的自发荧光图像可反映AMD发展的不同程度,动态监测异常自发荧光图像特征对评估AMD的发生、发展具有重要的临床意义.     

Glycoxidized particles mimic lipofuscin accumulation in aging eyes: a new age-related macular degeneration model in rabbits

Purpose The biogenesis of drusen, a hallmark of age-related macular degeneration (AMD), is still unclear. Lipofuscin, which extensively accumulates with age in RPE cells, is hardly soluble, derived in part from oxidation byproducts of the photoreceptor outer segments. The purpose of the current study is to develop a new AMD model in rabbits using glycoxidized particles as imitation lipofuscin, and determine whether accumulation of lipofuscin as insoluble material may play a role in drusen biogenesis and other pathogenesis of AMD. Methods To mimic the accumulation of insoluble lipofuscin, glycoxidized microspheres (glycox-MS) were made through a glycoxidation process with albumin and glycolaldehyde, α-hydroxy aldehyde. As a control, microspheres made with glutaraldehyde (cMS) and soluble glycoxidized (glycox-) albumin were prepared. Each material was implanted into the subretinal space in rabbits. The implanted area was assessed by funduscopy, fluorescein angiography, histology, and transmission electron microscopy (TEM). Results Compared with control microspheres, glycox-MS stagnated for a prolonged period in the cytoplasm of RPE cells. Eyes implanted with glycox-MS produced drusen-like deposits at a significantly higher frequency, when compared with the controls. Glycox-MS were observed at the margin of or beneath the drusen-like deposits in all cases. In some eyes with glycox-MS, late-onset sub-RPE choroidal neovascularization was observed, while control groups did not have these findings. Conclusions These results suggest that the accumulation of indigestible granules such as lipofuscin in RPE or subsequent depositions toward Bruch’s membrane may play a role in drusen biogenesis as a trigger of inflammation or via other mechanisms. This model of AMD may be useful to elucidate drusen biogenesis and pathogenesis of AMD. Presented in part at the Annual Meetings of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, FL, May 4, 2002 and May 5, 2003. Supported in part by German Research Community (DFG) grant WI 880/9-1.     

Autofluorescence distribution associated with drusen in age-related macular degeneration

PURPOSE: To determine whether drusen in patients with age-related maculopathy and macular degeneration (ARM/AMD) are associated with focal changes in retinal pigment epithelium (RPE) lipofuscin fluorescence. METHOD: A new autofluorescence imaging device was used to study lipofuscin distribution associated with individual drusen in 20 patients with ARM/AMD. Paired monochromatic and autofluorescence fundus images were used for detailed analysis of the topography of autofluorescence at specific sites containing drusen. In four eyes, image analysis was used to compare the spatial distribution of the autofluorescence with the location of drusen and to quantify the autofluorescence distribution over individual drusen (54 drusen). REsuLTs. A specific pattern of autofluorescence was frequently found to be spatially associated with hard drusen and soft drusen between 60 and 175 microm in size. The pattern is characterized by a central area of decreased autofluorescence surrounded, in most cases, by an annulus of increased autofluorescence. The location of this pattern was highly correlated with the position of individual distinct drusen. The central low autofluorescence focus was on average 16% below the surrounding background, and the annulus, when present, was on average 6% more fluorescent than the background. Soft drusen larger than 175 microm and confluent soft drusen show either multifocal areas of low autofluorescence or a more heterogeneous distribution. CONCLUSIoNs. Autofluorescence imaging permits measurement of RPE lipofuscin at specific sites. RPE overlying drusen have altered autofluorescence, suggesting changes in RPE health.     

Spectral profiling of autofluorescence associated with lipofuscin,Bruch's Membrane,and sub-RPE deposits in normal and AMD eyes

PURPOSE: To compare the autofluorescence spectra of retinal pigment epithelium (RPE)-associated lipofuscin, Bruch's membrane, and sub-RPE deposits (drusen and basal laminar-linear deposits) in eyes of donors with age-related macular degeneration (AMD) against eyes of age-matched control donors. METHODS: Cryosections were cut from the maculae of unfixed human donor eyes with AMD or from age-matched control eyes. Tissues were excited at wavelengths of 364, 488, 568, and 633 nm. Emission spectra were collected with a confocal microscope equipped with a spectrophotometric detector at 10-nm wavelength intervals between 400 and 800 nm. RESULTS: RPE lipofuscin had strong autofluorescent emissions that were excited at all wavelengths. Bruch's membrane exhibited strong autofluorescence with an emission peak of 485 +/- 5 nm when excited with 364-nm light. At 488-, 568-, and 633-nm excitations, Bruch's membrane and sub-RPE deposits in normal eyes exhibited minimal autofluorescence. In AMD eyes, however, both the 364- and 488-nm excitation wavelengths stimulated substantial blue-green emissions from sub-RPE deposits and Bruch's membrane, with average pixel intensities substantially exceeding that elicited in the yellow-orange range by RPE lipofuscin. CONCLUSIONS: These data suggest that an increase in blue-green autofluorescence of Bruch's membrane relative to the yellow-orange autofluorescence of RPE-associated lipofuscin is associated with AMD. Knowledge of these spectra will be useful in evaluating animal models of macular degenerative disease and in diagnosis of AMD, and will provide a novel signature for further analysis of the molecular entities emitting these fluorescent signatures.     

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.     

Review of fundus autofluorescence in choroidal melanocytic lesions

Fundus autofluorescence (FAF) imaging takes advantage of the fluorescent properties of some molecules, especially lipofuscin. FAF derives mainly from retinal pigment epithelium (RPE) and Bruch's membrane. Using confocal scanning laser ophthalmoscope (cSLO) we have previously shown that FAF associated with pigmented choroidal lesions can be attributed to mainly lipofuscin (orange pigment) within the RPE. Other causes of FAF include hyperpigmentation, drusen, or fibrous metaplasia probably because they also cause lipofuscin accumulation in the overlying RPE. There is a total or partial correlation between FAF and the foci of lipofuscin and hyperpigmentation in about 90% of the cases. The FAF patterns of choroidal melanocytic lesions were classified as patchy or diffuse. The patchy pattern was defined as the presence of distinct areas of increased FAF between areas of normal autofluorescence. The diffuse pattern was characterized by the presence of increased FAF with indistinct borders over a larger part (>50%) of the tumour in the absence of such intervening areas. Choroidal melanomas presented with either a diffuse or patchy pattern, whereas choroidal naevi demonstrated only the patchy pattern. Diffuse FAF pattern was more often associated with larger choroidal melanomas as well as with early venous and late hyperfluorescence on fluorescein angiography. Limitations of these observations depend on the field of depth of cSLO; thus, FAF from other planes could not be detected. Increased retinal thickness, intraretinal oedema, or presence of subretinal fluid may also affect the FAF signal.     

Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration

PURPOSE: To test if fundus autofluorescence (FAF) patterns around geographic atrophy (GA) have an impact on GA progression rates over time in atrophic age-related macular degeneration (AMD). DESIGN: Prospective longitudinal multicenter natural history study. METHODS: Standardized digital FAF images were obtained from 195 eyes of 129 patients with GA using confocal scanning laser ophthalmoscopy (excitation 488 nm, emission >500 nm). Areas of GA were quantified and patterns of abnormal FAF in the junctional zone were classified. Repeated FAF images were obtained over a median follow-up period of 1.80 years (interquartile range [IQR], 1.28 to 3.34). RESULTS: Areas of GA (median, 7.04 mm(2) at baseline; IQR, 3.12 to 10.0) showed a median enlargement of 1.52 mm(2)/year (IQR, 0.81 to 2.33). Progression rates in eyes with the banded (median 1.81 mm(2)/year) and the diffuse FAF pattern (1.77 mm(2)/year) were significantly higher compared to eyes without FAF abnormalities (0.38 mm(2)/year) and focal FAF patterns (0.81 mm(2)/year, P < .0001). Within the group of the diffuse pattern, eyes with a diffuse trickling pattern could be identified that exhibited an even higher spread rate (median 3.02 mm(2)/year) compared to the other diffuse types (1.67 mm(2)/year, P = .001). CONCLUSIONS: The results indicate that distinct phenotypic FAF patterns have an impact on disease progression in eyes with atrophic AMD and may therefore serve as prognostic determinants. The findings underscore the relevance of FAF imaging and the pathogenetic role of excessive retinal pigment epithelium (RPE) lipofuscin (LF) accumulation in GA. Natural history data and identification of high-risk characteristics will be helpful to design interventional studies aiming at slowing the spread of atrophy.     

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。     

Pathophysiology of age-related macular degeneration

The clinical and histopathological features of age-related macular degeneration (AMD) include a relationship with age, and the presence of pigmentary disturbances, drusen, thickening of Bruch's membrane, and basal laminar deposits. AMD is an advanced stage of a deteriorative process that takes place in all eyes. The primary lesion in AMD appears to reside in the retinal pigment epithelium (RPE), possibly resulting from its high rate of molecular degradation. Beginning early in life, and continuing throughout the life span, cells of the RPE gradually accumulate sacs of molecular debris. These residual bodies (lipofuscin) are remnants of the incomplete degradation of abnormal molecules which have been damaged within the RPE cells or derived from phagocytized rod and cone membranes. Progressive engorgement of RPE cells with these functionless residues is associated with the extrusion of aberrant materials which accumulate in Bruch's membrane and aggregate in the form of drusen and basal laminar deposits. These excretions contribute to the further deterioration of the RPE. Loss of vision results from death of visual cells due to degeneration of RPE cells, or the effects of leakage from neovascular membranes that invade the region of abnormal extracellular deposits.     

Fundus autofluorescence in choroidal melanocytic lesions

PURPOSE: To correlate fundus autofluorescence (FAF) patterns in choroidal melanocytic lesions with changes present on the surface of such lesions, including lipofuscin, hyperpigmentation, drusen, and fibrous metaplasia. METHODS: Retrospective chart review for 23 consecutive patients with choroidal nevi and melanoma who underwent FAF photography. The correlation between increased FAF patterns and foci of lipofuscin, hyperpigmentation, drusen, or fibrous metaplasia was defined as complete correlation, partial correlation, or no correlation. RESULTS: Lipofuscin was present in 13 tumors, hyperpigmentation was present in 9 tumors, drusen were present in 6 tumors, and fibrous metaplasia was present in 4 tumors. Complete correlation between increased FAF and lipofuscin was found in 8 tumors (61.5%); partial correlation, in 3 tumors (23.1%); and no correlation, in 2 tumors (15.4%). Complete correlation between hyperpigmentation and increased FAF was found in 5 tumors (55.6%); partial correlation, in 3 tumors (33.3%); and no correlation, in 1 tumor (11.1%). Partial correlation was found between drusen and increased FAF in 4 tumors. Partial correlation was found between fibrous metaplasia and increased FAF in three tumors. CONCLUSION: Choroidal melanocytic lesions with overlying lipofuscin and hyperpigmentation are associated with increased FAF in approximately 90% of cases.     

Correlation between the area of increased autofluorescence surrounding geographic atrophy and disease progression in patients with AMD

PURPOSE: To test the hypothesis that the extension of areas with increased fundus autofluorescence (FAF) outside atrophic patches correlates with the rate of spread of geographic atrophy (GA) over time in eyes with age-related macular degeneration (AMD). METHODS: The database of the multicenter longitudinal natural history Fundus Autofluorescence in AMD (FAM) Study was reviewed for patients with GA recruited through the end of August 2003, with follow-up examinations within at least 1 year. Only eyes with sufficient image quality and with diffuse patterns of increased FAF surrounding atrophy were chosen. In standardized digital FAF images (excitation, 488 nm; emission, >500 nm), total size and spread of GA was measured. The convex hull (CH) of increased FAF as the minimum polygon encompassing the entire area of increased FAF surrounding the central atrophic patches was quantified at baseline. Statistical analysis was performed with the Spearman's rank correlation coefficient (rho). RESULTS: Thirty-nine eyes of 32 patients were included (median age, 75.0 years; interquartile range [IQR], 67.8-78.9); median follow-up, 1.87 years; IQR, 1.43-3.37). At baseline, the median total size of atrophy was 7.04 mm2 (IQR, 4.20-9.88). The median size of the CH was 21.47 mm2 (IQR, 15.19-28.26). The median rate of GA progression was 1.72 mm2 per year (IQR, 1.10-2.83). The area of increased FAF around the atrophy (difference between the CH and the total GA size at baseline) showed a positive correlation with GA enlargement over time (rho=0.60; P=0.0002). CONCLUSIONS: FAF characteristics that are not identified by fundus photography or fluorescein angiography may serve as a prognostic determinant in advanced atrophic AMD. As the FAF signal originates from lipofuscin (LF) in postmitotic RPE cells and since increased FAF indicates excessive LF accumulation, these findings would underscore the pathophysiological role of RPE-LF in AMD pathogenesis.     

Fundus Autofluorescence Imaging in Age-Related Macular Degeneration

Abstract

Fundus autofluorescence (FAF) is a noninvasive imaging technology that provides information on the distribution of lipofuscin within the retinal pigment epithelial cells. Progressive accumulation of lipofuscin within retinal pigment epithelial cells is involved in the pathogenesis of age-related macular degeneration (AMD). Fundus autofluorescence imaging using a confocal scanning laser ophthalmoscope is a useful technique to identify high-risk characteristics in patients with nonexudative AMD. It gives also some valuable knowledge and clues in differantial diagnosis of exudative age-related macular degeneration. This review comprises an introduction to fundus autofluorescence, a review of FAF imaging in AMD, and the recent classification of geographic atrophy (GA) and early AMD phenotypes by the Fundus Autofluorescence in Age-related Macular Degeneration Study. The association of phenotype and atrophy progression and choroidal neovascularization development are also summarized.     

Multimodal morphological and functional characterization of Malattia Leventinese

Background

To analyze the morphological and functional characteristics of malattia leventinese.

Methods

This was a chart review of patients with Malattia Leventinese. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). Microperimetry and Preferential Hyperacuity Perimeter (PHP) were performed in a subset of patients.

Results

Twelve eyes of six patients were included. BCVA ranged from 20/25 to 20/200. The largest drusen were round, not radially distributed, localized in the perimacular area and around the optic disc. The smallest drusen were not round, radially distributed, mostly localized temporally to the macula. FAF revealed an intense autofluorescence of large drusen. On both FA and ICGA, large round drusen turned to hyperfluorescent in the late phase, while small radial drusen progressively decreased their fluorescence. OCT showed the large round drusen as focal or diffuse deposition of hyperreflective material between the RPE and Bruch membrane within the macula, determining focal dome-shaped or diffuse RPE elevation respectively, and the small radial drusen, which ranged from irregular slight thickening of the RPE/Bruch membrane complex to sawtooth RPE elevation. In three patients (six eyes) that underwent microperimetry and PHP, there was a good correspondence between macular sensitivity and PHP score. Functional impairment correlated topographically to sub-RPE deposition of drusenoid material.

Conclusions

In this series, large round drusen of Malattia Leventinese appeared similar to drusen in age-related macular degeneration, while small radial drusen of Malattia Leventinese shared similarities with early-onset cuticular drusen.     

Fundus autofluorescence of choroidal nevus and melanoma

BACKGROUND: To describe autofluorescence patterns of choroidal melanocytic lesions using the Heidelberg Retinal Angiograph 2 system (HRA2). METHODS: 20 patients with choroidal melanocytic lesions in the ocular fundus underwent ophthalmologic examination, fundus photography, autofluorescence and optical coherence tomography (OCT). Pathologic examination was performed on one enucleated eye with a large choroidal melanoma. RESULTS: 15 patients had choroidal nevi and 5 had malignant choroidal melanoma (1 small, 1 medium and 3 large tumours). Choroidal nevi did not show any characteristic autofluorescence pattern, although secondary retinal pigment epithelium (RPE) changes, such as drusen and pigment epithelium detachment, appeared faintly hyperautofluorescent in 2 patients. Only the small malignant choroidal melanomas had prominent orange pigmentation, although all melanomas had an intense confluent hyperautofluorescent signal over the lesions. Pathology of one large malignant melanoma revealed lipofuscin underlying RPE. CONCLUSION: Most nevi did not have characteristic hyperautofluorescent features, but choroidal melanomas seemed to have a pattern of confluent hyperautofluorescence. Therefore, autofluorescence may be a useful non-invasive tool to assess lipofuscin in pigmented choroidal lesions, which may contribute to the diagnosis of malignancy. This hypothesis, however, remains to be confirmed in large prospective studies.     

Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in age-related macular degeneration

PURPOSE: To assess the relationships of drusen, pigment, and focally increased autofluorescence (FIAF) and the reticular pattern of hypoautofluorescence, to distinguish the combined photographic and AF characteristics of early, atrophic, and high-risk fellow eyes in AMD. METHODS: In a retrospective interinstitutional clinical study, AF and color photograph pairs of 221 eyes were examined: 166 eyes of 83 patients with bilateral large, soft drusen, with and without geographic atrophy (GA), and 55 fellow eyes of 55 patients with unilateral choroidal neovascularization (CNV). Forty-two eyes (one eye from each of 42 patients with early or atrophic AMD) were divided into four groups: 14 with drusen only, 9 with drusen and pigment abnormalities, 11 fellow eyes of patients with unilateral GA, and 8 eyes of patients with bilateral GA (acronyms for the groups: D-D, D-Pig, D-GA and GA-GA, respectively). The 55 fellow eyes of patients with CNV were divided into three groups: 19 eyes with no FIAF (CNV-0), 16 with FIAF without reticular AF (CNV-1), and 20 eyes with reticular AF and/or pseudodrusen (CNV-R). Image pairs of eyes with FIAF were registered, and drusen, pigment, and FIAF were segmented using automated background leveling and thresholding. All 221 eyes were surveyed for reticular AF and reticular pseudodrusen. The main outcome measures were (1) the fraction and relative probability of FIAF colocalizing with drusen and pigment and (2) the presence or absence of reticular AF and reticular pseudodrusen. RESULTS: The mean fractions of FIAF that colocalized with large drusen were: D-D group, 0.46 +/- 0.21; D-Pig group, 0.42 +/- 0.29; D-GA group, 0.13 +/- 0.09; and GA-GA group, 0.11 +/- 0.12. Comparisons between groups showed significant differences when comparing either the D-D group or the D-Pig group with either the D-GA group or the GA-GA group (P between 0.0001 and 0.015), whereas other comparisons were nonsignificant (Mann-Whitney rank sum test). The mean probabilities of FIAF colocalizing with large drusen relative to chance (1.0) were: D-D group, 4.7 +/- 2.5; D-Pig group, 4.3 +/- 2.3; D-GA group, 1.4 +/- 0.8; and GA-GA group, 1.8 +/- 1.3, with similar significant differences as for the colocalization fractions. The mean probability of FIAF colocalizing with small to intermediate drusen in the D-D group was 1.5 +/- 1.3, which was not significantly different from chance. In the D-Pig group, the median probability of FIAF colocalizing with pigment abnormalities was 10.0 (range, 1.1-51.0). The AF patterns in 15 of 19 eyes in the CNV-0 group were normal; the remainder had nonreticular hypoautofluorescence only. In the CNV-1 group, the relations of FIAF with drusen and pigment were similar to those in the early AMD groups. CNV-R comprised 20 of 55 eyes in the CNV group, but reticular autofluorescence and/or pseudodrusen were found in only 14 of 166 eyes of the early and atrophic groups. Of the 34 total eyes with reticular AF or pseudodrusen, 28 had both, 4 had reticular AF only, and 2 had reticular pseudodrusen only. CONCLUSIONS: There are clear relationships between AF patterns and clinical AMD status. In early AMD, FIAF's colocalization with large, soft drusen and hyperpigmentation is several times greater than chance, suggesting linked disease processes. In advanced atrophic AMD, FIAF is found mostly adjacent to drusen and GA, suggesting that dispersal of drusen-associated lipofuscin is a marker of atrophic disease progression. In the neovascular case, a large group of fellow eyes have no FIAF abnormalities, suggesting that lipofuscin is not a major determinant of CNV. However, reticular hypoautofluorescence, consistent with widespread inflammatory damage to the RPE, appears to be a highly sensitive imaging marker for the disease that determines reticular pseudodrusen and is strongly associated with CNV.     

Microperimetry and fundus autofluorescence in patients with early age-related macular degeneration

BACKGROUND: Early age-related macular degeneration (AMD) has been correlated with different functional alterations, but the exact relationship between fundus lesions and overlying sensitivity is not well known. The aim of this study was to compare fundus-related sensitivity (microperimetry) and fundus autofluorescence (FAF) of the macular area with drusen and pigment abnormalities in early AMD. METHODS: 13 consecutive patients with early AMD and visual acuity of 20/20 were studied by means of microperimetry, which automatically analyses macular light differential threshold and fixation patterns. Fundus colour photo and FAF of the macular area were recorded on the same day. Microperimetry was exactly (topographically) superimposed over FAF images. RESULTS: Macular sensitivity significantly decreased over large drusen (11.2 +/- 5.6 dB, p<0.0001) and over pigment abnormalities (13.1 +/- 3.6 dB, p<0.0001). When both characteristics were present the reduction was greater if compared with its absence (9.6 +/- 4.3 versus 15.0 +/- 4.5 dB, p<0.0001). Sensitivitity reduction was significant in areas with altered FAF when compared with areas with normal FAF (p<0.0001). CONCLUSIONS: Increased FAF in early AMD has a functional correlate exactly quantified by microperimetry. In retinal areas affected by early AMD retinal sensitivity deteriorates, despite good visual acuity. Microperimetry may allow the early detection of functional impairment caused by these lesions. Both microperimetry and FAF may be useful to monitor AMD progression.     

萎缩型老年性黄斑变性的吲哚青绿和荧光素眼底血管造影观察

目的 观察和评价萎缩型老年性黄斑变性(age-related macular degeneratioin, AMD)的荧光素眼底血管造影(fundus fluoresce in angiography, FFA)与吲哚青绿血管造影(indocyanine green angiography, ICGA)图像特征和对比检查的应用价值。 方法 回顾分析73例萎缩型AMD患者95只眼的彩色眼底照相、FFA和ICGA检查资料，其中包括视网膜色素上皮(retinal pigment epithelium, RPE)色素脱失与萎缩19例26只眼、玻璃疣15例30只眼和39例单侧渗出性AMD患者的对侧眼39只。 结果 26只RPE色素脱失与萎缩的眼中，24只色素脱失眼 FFA表现为晚期斑片状强荧光，ICGA表现为斑片状强弱相间荧光；地图状萎缩2只眼，FFA表现为斑片状强荧光，ICGA表现为边界清晰的弱荧光内见脉络膜毛细血管缺损，仅有脉络膜大血管。8只硬性玻璃疣眼FFA表现为强荧光，ICGA表现为持续斑点状 强荧光；16只软性玻璃疣眼FFA表现为强荧光，ICGA表现为持续性斑片状强弱相间荧光；6只同时有软性和硬性玻璃疣眼FFA表现为强荧光，ICGA表现为斑点状强弱相间荧光。当玻璃疣ICGA表现为弱荧光时，FFA所见到的玻璃疣的数量及范围较ICGA 所见者更多更大；当玻璃疣ICGA表现为强荧光时，FFA检查所见到的玻璃疣的数量及范围较ICGA所见更少。单侧渗出型AMD对侧39只眼中，ICGA检查发现32只眼、FFA检查发现31只眼有玻璃疣及RPE色素脱失与萎缩的异常荧光。 结论 ICGA与FFA同步检查为观察萎缩型AMD的眼底图像特征提供了完善的检查手段。 （中华眼底病杂志，2003，19：79-82）     

周边部视网膜病变相关区域的自发荧光表现

目的 观察周边部视网膜病变相关区域的自发荧光(AF)表现.方法 42例周边部视网膜病变患者60只眼纳入本研究.所有患者均经全景眼底视网膜照相和荧光素眼底血管造影(FFA)检查确诊.应用共焦激光眼底血管造影仪HRAⅡ行黑色素相关近红外自发荧光(NIA)及脂褐质相关自发荧光(FAF)检查,分别采用波长为795、488 nm的激光激发成像.记录9张/s,由共焦激光眼底血管造影仪HRAⅡ自动合成高分辨影像视野为55°,像素为822×768的最终AF像.将AF像是否可见眼底血管及相关视网膜组织成像的影像判断为有、无价值AF像.病变区域是否出现符合正常血管和视网膜组织的荧光表现判断为正常、异常荧光.通过与图像背景灰度比较,将异常荧光分级为无荧光、弱荧光和强荧光,观察周边部视网膜病变相关区域的AF表现.对比分析NIA和FAF检查AF像均呈异常荧光表现者的异常荧光分级的一致性.结果 60只眼中,获取有价值AF像者53只眼,占88.33%;获取无价值AF像者7只眼,占11.67%.NIA检查显示,获取有价值AF像的53只眼中正常荧光28只眼,占52.83%;呈片状、圆点斑状、条带状异常荧光25只眼,占47.17%.FAF检查显示,获取有价值AF像的53只眼中正常荧光2只眼,占3.77%;呈片状或与色素分布较为一致或沿血管分布的异常荧光51只眼,占96.23%.两种检查均呈异常荧光表现的25只眼中,异常荧光分级一致者18只眼,占72.00%;异常荧光分级不一致者7只眼,占28.00%.结论 周边部视网膜病变相关区域存在不同程度的AF表现.

Abstract：

Objective To observe the autofluorescence (AF) manifestation in related lesions of periphery retinopathy. Methods Sixty eyes of 42 patients with periphery retinopathy underwent the examination of Optomap fundus photograph (200°) and fundus fluorescein angiography (FFA). The HRA Ⅱ melanin-related near-infrared fundus autofluorescence (NIA, excitation 795 nm) and lipofuscin-related fundus autofluorescence (FAF, excitation 488 nm) were measured for all the patients. The AF was recorded with nine images per second, and then a final AF image with 55° view and 822 × 768 pixel was generated by the HRA. AF images can be valuable or valueless if there was or was not visible blood vessels and related retinal tissues on the image. AF from lesion regions can be normal or abnormal fluorescence comparing to the normal vascular and retinal tissue AF. The abnormal fluorescence was divided into no AF, weak AF and strong AF relative to the background grayscale. The grading consistency of abnormal fluorescence based on FAF and NIA examination was comparatively analyzed. Results Valuable AF images were captured in 53/60 eyes (88. 33%)and valueless AF images were captured in 7/60 eyes (11.67%). Among 53 eyes with valuable AF image, NIA showed normal fluorescence in 28 eyes (52. 83%), abnormal fluorescence with sheet-like, dot-shaped or stripped in 25 eyes (47.17%); FAF showed normal fluorescence in two eyes (3.77 % ), abnormal fluorescence with sheet-like, scattered along vessels or pigments in 51 eyes (96.23 % ).Twenty-five eyes with abnormal fluorescence were observed both in two examinations, including same grades in 18 eye (72.00%) and different grades in seven eyes (28.00%). Conclusion The AF manifestation with different levels exists in related lesions of periphery retinopathy.     

Autofluorescent Organelles Within the Retinal Pigment Epithelium in Human Donor Eyes With and Without Age-Related Macular Degeneration

PurposeHuman retinal pigment epithelium (RPE) cells contain lipofuscin, melanolipofuscin, and melanosome organelles that impact clinical autofluorescence (AF) imaging. Here, we quantified the effect of age-related macular degeneration (AMD) on granule count and histologic AF of RPE cell bodies.MethodsSeven AMD-affected human RPE-Bruch''s membrane flatmounts (early and intermediate = 3, late dry = 1, and neovascular = 3) were imaged at fovea, perifovea, and near periphery using structured illumination and confocal AF microscopy (excitation 488 nm) and compared to RPE-flatmounts with unremarkable macula (n = 7, >80 years). Subsequently, granules were marked with computer assistance, and classified by their AF properties. The AF/cell was calculated from confocal images. The total number of granules and AF/cell was analyzed implementing a mixed effect analysis of covariance (ANCOVA).ResultsA total of 152 AMD-affected RPE cells were analyzed (fovea = 22, perifovea = 60, and near-periphery = 70). AMD-affected RPE cells showed increased variability in size and a significantly increased granule load independent of the retinal location (fovea: P = 0.02, perifovea: P = 0.04, and near periphery: P < 0.01). The lipofuscin fraction of total organelles decreased and the melanolipofuscin fraction increased in AMD, at all locations (especially the fovea). AF was significantly lower in AMD-affected cells (fovea: <0.01, perifovea: <0.01, and near periphery: 0.02).ConclusionsIn AMD RPE, lipofuscin was proportionately lowest in the fovea, a location also known to be affected by accumulation of soft drusen and preservation of cone-mediated visual acuity. Enlarged RPE cell bodies displayed increased net granule count but diminished total AF. Future studies should also assess the impact on AF imaging of RPE apical processes containing melanosomes.     

Drusenoid maculopathy in rhesus monkeys: autofluorescence, lipofuscin and drusen pathogenesis

PURPOSE: To examine patterns of retinal pigment epithelial autofluorescence and lipofuscin accumulation in relation to drusen and to explore the pathogenesis of drusen in rhesus monkeys. METHODS: The macular areas of six rhesus monkeys, euthanized at 19 to 28 years of age, were studied by bright field and fluorescence light microscopy and transmission electron microscopy. RESULTS: There was strong autofluorescence in the retinal epithelium that tended to diminish over drusen. Electron microscopy revealed that all retinal epithelial cells had large concentrations of lipofuscin bodies. The epithelial cells overlying drusen, however, tended to have less lipofuscin than epithelial cells not associated with drusen. Electron microscopy revealed that the epithelial cells overlying drusen were losing segments of cytoplasm containing lipofuscin bodies. Macrophage-like cells were consistently present in Bruch's membrane microns away from this lipofuscin-containing cytoplasmic material. CONCLUSIONS: Retinal epithelial cells overlying drusen have less lipofuscin than neighboring epithelial cells. The loss of lipofuscin seems due to a loss of cytoplasm containing lipofuscin that contributes to drusen formation. Macrophages in Bruch's membrane may be responsible for removing this lipofuscin debris. The results support in vivo studies showing reduced autofluorescence over drusen and support the "budding" of epithelial cytoplasm as a source of drusen material.