Fundus autofluorescence in central serous chorioretinopathy:association with spectral-domain optical coherence tomography and fluorescein angiography

AIM: To evaluate the correlation among changes in fundus autofluorescence (AF) measured using infrared fundus AF (IR-AF) and short-wave length fundus AF (SW-AF) with changes in spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA) in central serous chorioretinopathy (CSC).METHODS:Two hundred and twenty consecutive patients with CSC were included. In addition to AF, patients were assessed by means of SD-OCT and FA. Abnormalities in images of IR-AF, SW-AF, FA were analyzed and correlated with the corresponding outer retinal alterations in SD-OCT findings.RESULTS:Eyes with abnormalities on either IR-AF or SW-AF were found in 256 eyes (58.18%), among them 256 eyes (100%) showed abnormal IR-AF, but SW-AF abnormalities were present only in 213 eyes (83.20%). The hypo-IR-AF corresponded to accumulation of sub-retinal liquid, collapse of retinal pigment epithelium (RPE) or detachment of RPE with or without RPE leakage point in the corresponding area. The hyper-IR-AF corresponded to the area with loss of the ellipsoid portion of the inner segments and sub-sensory retinal deposits or focal melanogenesis under sensory retina. The hypo-SW-AF corresponded to accumulation of sub-retinal liquid or atrophy of RPE. The hyper-SW-AF associated with sub-sensory retinal deposits, detachment of RPE and focal melanogenesis.CONCLUSION:IR-AF was more sensitive than SW-AF and FA for identifying pathological abnormalities in CSC. The characteristics of IR-AF in CSC were attributable to the modification of melanin in the RPE. IR-AF should be used as a common diagnostic tool for identifying pathological lesion in CSC.KEYWORDS:central serous chorioretinopathy; fluorescein angiography; fundus autofluorescence; optical coherence tomography     

The bisretinoids of retinal pigment epithelium

The retina exhibits an inherent autofluorescence that is imaged ophthalmoscopically as fundus autofluorescence. In clinical settings, fundus autofluorescence examination aids in the diagnosis and follow-up of many retinal disorders. Fundus autofluorescence originates from the complex mixture of bisretinoid fluorophores that are amassed by retinal pigment epithelial (RPE) cells as lipofuscin. Unlike the lipofuscin found in other cell-types, this material does not form as a result of oxidative stress. Rather, the formation is attributable to non-enzymatic reactions of vitamin A aldehyde in photoreceptor cells; transfer to RPE occurs upon phagocytosis of photoreceptor outer segments. These fluorescent pigments accumulate even in healthy photoreceptor cells and are generated as a consequence of the light capturing function of the cells. Nevertheless, the formation of this material is accelerated in some retinal disorders including recessive Stargardt disease and ELOVL4-related retinal degeneration. As such, these bisretinoid side-products are implicated in the disease processes that threaten vision. In this article, we review our current understanding of the composition of RPE lipofuscin, the structural characteristics of the various bisretinoids, their related spectroscopic features and the biosynthetic pathways by which they form. We will revisit factors known to influence the extent of the accumulation and therapeutic strategies being used to limit bisretinoid formation. Given their origin from vitamin A aldehyde, an isomer of the visual pigment chromophore, it is not surprising that the bisretinoids of retina are light sensitive molecules. Accordingly, we will discuss recent findings that implicate the photodegradation of bisretinoid in the etiology of age-related macular degeneration.     

Fundus autofluorescence after selective RPE laser treatment

BACKGROUND: The selective RPE laser treatment is a new technique which selectively damages the RPE and avoids adverse effects to the neural retina. A problem is the ophthalmoscopically non-visibility of the laser lesions. The aim of the study was to investigate whether fundus autofluorescence (AF), which is derived from the lipofuscin contained by the RPE cells, is changed due to the RPE damage, and thus may be used for non-invasive treatment control. METHODS: A total of 26 patients with macular diseases, i.e. diabetic maculopathy (DMP), soft drusen maculopathy (AMD) and central serous retinopathy (CSR), were treated with repetitive short laser pulses (800 ns) from a green Nd:YAG laser (parameters: 532 nm, 100 and 50 pulses at 500 and 125 Hz, retinal spot diameter 200 micrometer, pulse energies 70-175 microJ). AF was excited by 488 nm and detected by a barrier filter at 500 nm (HRA, Heidelberg engineering). Patients were examined by ophthalmoscopy, fluorescein angiography and autofluorescence measurements at various times after treatment (i.e. 1 h, 1 and 6 weeks, 3, 6 and 12 months). RESULTS: None of the laser lesions was ophthalmoscopically visible during treatment although fluorescein angiography showed leakage of the irradiated areas. Identification of the lesions was possible by AF imaging showing an intensity decay in the irradiated area in 22 out of 26 patients, predominantly in patients with CSR and AMD. Lesions could be identified as hypoautofluorescent spots 1 h after treatment. During follow-up the laser spots became hyperautofluorescent. In patients with DMP some AF images were less helpful due to diffuse edema and larger retinal thickness. CONCLUSION: Imaging of non-visible selective RPE laser effects can be achieved by AF measurements predominantly in patients without retinal edema. Thus AF may replace invasive fluorescein angiography in many cases to verify therapeutic laser success.     

Spectral domain optical coherence tomography in a murine retinal detachment model

Spectral domain optical coherence tomography (SD-OCT) was used to image retinal detachments in vivo, in a murine model of retinal detachment (RD). Subretinal injections of hyaluronic acid (Healon) were delivered to the right eye of seventeen 10-20 week-old C57Bl6 mice. Evaluation of the fundus with an operating microscope and fundus photography were performed. In vivo, non-contact, ultra high resolution SD-OCT imaging was performed on day 0, day 1-2, day 5-6 and day 15-16. The retinal morphology at the edge and in the area of maximal RD was evaluated. Eyes were enucleated for histologic analysis. The retinal detachment was confirmed by microscopy in all mice. The extent of the retinal detachment was evaluated by measuring the height of the retinal detachment. The retinal layers, including the photoreceptor layer, were evaluated. Retinal layers appeared indistinct soon after RD (day 1, 5), particularly over areas of maximal detachment. By day 5 and 15 the external limiting membrane was no longer visible and there was increased reflectivity of the photoreceptor layer and undulation of the outer retina in areas of RD on both SD-OCT and histology. The thickness of the outer nuclear layer and photoreceptor outer segments decreased on day 5 and 15. SD-OCT is a promising technology to follow retinal detachment and outer retinal abnormalities in a murine model.     

部分眼底病红外线及自发荧光影像特点初步观察

目的观察部分眼底病眼底红外线（infrared ray,IR）和自发荧光（autofluorescence,AF）的影像特征。方法采用HRA-2共焦激光扫描系统的IR模式和FA模式检测73例（85眼）眼底病患者,其中年龄相关性黄斑变性25例（34眼）,中心性浆液性脉络膜视网膜病变16例（16眼）,黄斑裂孔5例（5眼）,视网膜静脉阻塞17例（17眼）,前部缺血性视神经病变（anterior ischemic optic neuropathy,AION）10例（13眼）。结果年龄相关性黄斑变性的IR影像见散在不规则白色病灶,AF影像呈低信号,边缘见环形高信号。中心性浆液性脉络膜视网膜病变的IR影像为异常范围大于AF影像所见。全层黄斑裂孔的IR影像见白色斑点,AF影像呈圆形高信号。IR影像在显示视网膜静脉阻塞黄斑水肿边缘方面优于AF。AION的AF呈低信号。结论IR影像不同于以往的其他检查方法,可以揭示较深层次的视网膜病变。眼底出血时AF表现为遮蔽,视网膜下积液导致荧光信号降低,脂褐质积累荧光信号增强。IR和AF影像是评价视网膜尤其是视网膜色素上皮的有效方法。     

N-cadherin expression in a rat model of retinal detachment and reattachment

PURPOSE: To observe the changes in N-cadherin expression in the retina after experimental retinal detachment (RD) and reattachment in the rat and to explore the role N-cadherin might play after RD. METHODS: Forty rat retinas were detached by transscleral injection of 1.4% sodium hyaluronate into the subretinal space. The eyes were enucleated at different time intervals (n = 5), followed by fixation, embedding, and sectioning. The differences in N-cadherin expression in the normal retina, detached retina, and spontaneously reattached retina were determined. Furthermore, an N-cadherin antagonist was injected in combination with 1.4% sodium hyaluronate into the subretinal space in another 10 eyes, in an attempt to demonstrate the role N-cadherin plays after RD. RESULTS: N-cadherin was not expressed in the RPE layer of the normal rat retina. After RD, intense immunolabeling of N-cadherin was seen in the RPE cells, the photoreceptors, and the outer limiting membrane (OLM). An increasing number of cytokeratin (CK)-positive cells likely to be RPE cells was found attached to the outer surface of the detached neural retina. Where the retina was reattached, the N-cadherin immunolabeling rapidly decreased. In eyes treated with an N-cadherin antagonist, the retinas appeared thinner than that in eyes without treatment, and the photoreceptor nuclei showed significantly loss. Moreover, CK-positive cells attached to the outer surface of the detached retina were markedly fewer in number. CONCLUSIONS: Increased expression of N-cadherin in the RPE cells, the photoreceptor cells, and the OLM of the retina after RD may contribute to RPE cell migration and photoreceptor survival. These changes could be reversed by retinal reattachment.     

Abnormalities of fundus autofluorescence in central serous retinopathy

PURPOSE: To report abnormalities of fundus autofluorescence associated with acute and chronic central serous retinopathy (CSR). DESIGN: A prospective cohort study of patients with CSR was undertaken in which the intensity and spatial distribution of fundus autofluorescence were documented. METHODS: Fundus autofluorescence was recorded using a confocal laser scanning ophthalmoscope (cLSO) and the images compared with the fundus appearance and fluorescein angiograms in 69 eyes of 63 subjects with either acute or chronic CSR. Areas of increased and decreased autofluorescence were compared with ophthalmoscopic and fluorescein angiography abnormalities. Thirty patients with focal leakage on angiography and serous retinal detachment or pigment epithelial detachment were designated as having acute CSR. Thirty-three patients with diffuse leakage on fluorescein angiography, but without manifest detachment were classified as having chronic CSR. RESULTS: The mean age was 39 years (range 29-56 years) 14 were female and 49 male. Acute CSR of more than 4 months duration showed a mild diffuse increase in autofluorescence that corresponded with the detached area. The leaking point on the angiogram corresponded to a focal area of intense autofluorescence. In chronic CSR the autofluorescence was very irregular, there being regions with greater and less than the background levels of fluorescence. CONCLUSION: In acute CSR, increased autofluorescence may occur at the site of leakage and in the area of retinal detachment probably indicating an increased metabolic activity of the retinal pigment epithelium (RPE). Decreased or absent autofluorescence in long-standing lesions may indicate reduced metabolic activity of the RPE due to photoreceptor cell loss. Documenting photoreceptor cell loss with autofluorescence imaging may be useful in identifying patients who would not benefit from laser photocoagulation.     

Autofluoreszenz-Imaging der Makula

Visualization of the retinal pigment epithelium (RPE) in vivo has proven difficult for various reasons, including the optical properties of the eye and the small size of the cellular elements, forming a single layer between the neurosensory retina and Bruch's membrane.With the advent of scanning laser ophthalmoscopy it is now possible to image topographic distribution and intensity fundus autofluorescence derived from accumulations of lipofuscin granules in RPE cells. Excessive lipofuscin storage in the RPE cytoplasm occurs not only in association with age but also with many hereditary and degenerative retinal diseases including age-related macular degeneration, Stargardt disease, Best disease, and pattern dystrophies. Lipofuscin in the RPE derives mainly from incomplete degradation of phagocytosed distal segments of photoreceptor outer segments, and is composed of various biomolecules including lipids, protein, and retinoids. Some of its constituents have recently been shown to possess toxic properties in vitro and may play a pathophysiological role in diseases such as age-related macular degeneration.Visualizing lipofuscin in vivo may help to better understand the significance of these metabolic alterations in the pathogenesis of retinal disorders. In addition,fundus autofluorescence imaging can be useful in the preclinical diagnosis of hereditary retinal disease. Dynamic alterations of intrinsic RPE fluorescence change may be applicable for monitoring effects at the level of the RPE of novel therapeutic modalities. Furthermore, identification of high-risk characteristics in patients with age-related macular degeneration with this technique may be helpful for indicating and adjusting future therapies.     

The susceptibility of the retina to photochemical damage from visible light

The photoreceptor/RPE complex must maintain a delicate balance between maximizing the absorption of photons for vision and retinal image quality while simultaneously minimizing the risk of photodamage when exposed to bright light. We review the recent discovery of two new effects of light exposure on the photoreceptor/RPE complex in the context of current thinking about the causes of retinal phototoxicity. These effects are autofluorescence photobleaching in which exposure to bright light reduces lipofuscin autofluorescence and, at higher light levels, RPE disruption in which the pattern of autofluorescence is permanently altered following light exposure. Both effects occur following exposure to visible light at irradiances that were previously thought to be safe. Photopigment, retinoids involved in the visual cycle, and bisretinoids in lipofuscin have been implicated as possible photosensitizers for photochemical damage. The mechanism of RPE disruption may follow either of these paths. On the other hand, autofluorescence photobleaching is likely an indicator of photooxidation of lipofuscin. The permanent changes inherent in RPE disruption might require modification of the light safety standards. AF photobleaching recovers after several hours although the mechanisms by which this occurs are not yet clear. Understanding the mechanisms of phototoxicity is all the more important given the potential for increased susceptibility in the presence of ocular diseases that affect either the visual cycle and/or lipofuscin accumulation. In addition, knowledge of photochemical mechanisms can improve our understanding of some disease processes that may be influenced by light exposure, such as some forms of Leber's congenital amaurosis, and aid in the development of new therapies. Such treatment prior to intentional light exposures, as in ophthalmic examinations or surgeries, could provide an effective preventative strategy.     

Chloroquine retinopathy: lipofuscin- and melanin-related fundus autofluorescence,optical coherence tomography and multifocal electroretinography

Purpose To evaluate melanin-related near-infrared fundus autofluorescence (NIA, excitation 787 nm, emission > 800 nm), lipofuscin-related fundus autofluorescence (FAF, excitation 488 nm, emission >500 nm), optical coherence tomography (OCT), and multifocal electroretinography (mfERG) in patients with chloroquine (CQ) retinopathy. Methods Two patients with progressed CQ retinopathy underwent clinical examination, ISCEV mfERG evaluation, and FAF and NIA imaging using a confocal scanning laser ophthalmoscope (Heidelberg Retina Angiograph 2) with either a 30° or wide-angle field-of-view. OCT3 imaging was performed in one of these patients. Results In the foveola, FAF and NIA were relatively normal. Parafoveal loss of retinal pigment epithelium (RPE) was indicated by absent FAF and NIA. An area of reduced FAF and NIA surrounded the parafoveal region of RPE loss. In the adjacent area, FAF was increased and increased NIA marked the peripheral border of increased FAF. Wide-field imaging revealed increased FAF in association with retinal vessels. Retinal thickness was markedly reduced in the OCT predominantly in the parafoveal region. Visual field loss and mfERG amplitude reduction corresponded to areas with increased or reduced FAF and NIA. Conclusion Patterns of FAF and NIA indicate different stages of pathophysiologic processes involving lipofuscin and melanin in the RPE. Combined retinal imaging and functional testing provides further insights in the pathogenesis and development of retinal degenerative disease. An association of CQ retinopathy with retinal vessels architecture is hypothesized.     

Shared Features in Retinal Disorders With Involvement of Retinal Pigment Epithelium

When using spectral domain optical coherence tomography (SD-OCT) to inform the status of outer retina, we have noted discrete hyperreflective lesions extending through photoreceptor-attributable bands that have a similar presentation in multiple retinal diseases. These lesions present as either corrugated thickenings of interdigitation zone and ellipsoid zone bands or in later stages as rectangular or pyramidal shaped foci that extend radially through photoreceptor cell-attributable bands. In ABCA4-related and peripherin-2/RDS-disease (PRPH2/RDS), monogenic forms of retinopathy caused by mutations in proteins expressed in photoreceptor cells, these punctate lesions colocalize with fundus flecks in en face images. In fundus albipunctatus and retinitis punctata albescens, diseases caused by mutations in genes (retinol dehydrogenase 5, RDH5; and retinaldehyde-binding protein 1, RLBP1) encoding proteins of the visual cycle, these lesions manifest as white dot-like puncta. Similar aberrations in photoreceptor cell-attributable SD-OCT reflectivity layers manifest as reticular pseudodrusen (RPD) in short-wavelength fundus autofluorescence and near-infrared fundus autofluorescence fundus images and are linked to age-related macular degeneration a complex disease. Despite differences in the etiologies of retinal diseases presenting as fundus flecks, dots and RPD, underlying degenerative processes in photoreceptor cells are signified in SD-OCT scans by the loss of structural features that would otherwise define healthy photoreceptor cells at these foci.     

Fundus autofluorescence in multifocal choroiditis and panuveitis

PURPOSE: To investigate the autofluorescence findings associated with multifocal choroiditis and panuveits (MCP), a condition that has marked potential to affect the retinal pigment epithelium (RPE). DESIGN: Observational case series. METHODS: This is a retrospective review of consecutive patients with MCP examined in a retinal referral practice. Each patient was given a comprehensive examination including fundus photographs, angiographic studies, and autofluorescence photography with an excitation filter with the bandpass wavelengths of 535 to 585 nm and a barrier filter with a bandpass of 615 to 715 nm. Integrative analysis was performed of the ocular imaging to ascertain abnormalities caused by the disease. RESULTS: Thirty-six eyes of 18 consecutive patients were evaluated. The mean duration of symptoms was 86.2 months and the mean visual acuity was 20/50. Of the 36 eyes, 23 had choroidal neovascularization (CNV). Chorioretinal hypoautofluorescent spots >or= 125 microns usually, but not always, had the clinically evident correlate of a punched-out scar visible by color fundus photography. Chorioretinal hypoautofluorescent spots less than 125 microns, which could number in the hundreds, typically were not visible by color fundus photography. All chorioretinal scars visible by color fundus photography were visible by autofluorescence photography. During follow-up many patients developed new clinically evident chorioretinal scars, which were presaged in earlier autofluorescence photographs. CNV had a hyperautofluorescent boundary, making it readily visible. CONCLUSIONS: Patients with MCP have much more widespread involvement of the RPE than would be suspected by other means of imaging. Autofluorescence photography supplies information about inflammatory damage and secondary CNV in a noninvasive manner.     

Effect of subthreshold infrared laser treatment for drusen regression on macular autofluorescence in patients with age-related macular degeneration

BACKGROUND: Subthreshold laser therapy has been shown to cause drusen reduction. Using this method, visible laser burns are not created in the retina; presumably, the energy is absorbed by the retinal pigment epithelium (RPE) and stimulates reabsorption of drusen material, sparing photoreceptors from destruction. We hypothesized that autofluorescence (AF) changes would be visible after such treatment and might be sensitive to quantify RPE changes. METHODS: Twenty eyes of 13 patients with non-exudative age-related macular degeneration were studied. Forty-eight subthreshold infrared diode laser spots were applied as treatment to cause drusen regression. Before, immediately after, and 3 months after treatment, color fundus photography, fluorescein angiography (FA), and autofluorescence (AF) imaging were performed. Treated lesions were identified on overlay images of all three imaging methods. RESULTS:: The averaged sensitivity of AF imaging compared with FA was 29.6+/-28.7% versus 10.2+/-12.2% (P=0.008) at the immediate posttreatment time point and 43.5+/-28.7% versus 33.8+/-26.5% (P=0.043) at the 3-month posttreatment time point, respectively. Reduction of drusen at 3 months correlated with the detection sensitivity of AF imaging at the immediate posttreatment time point (P=0.022). CONCLUSION: Immediately after subthreshold laser treatment, AF imaging was more sensitive to detect RPE changes than FA. This suggests that noninvasive AF imaging may allow prediction of the effect of subthreshold laser treatment and might be used to titrate treatment dose.     

Lipofuscin and the Principles of Fundus Autofluorescence: A Review

Fundus autofluorescence is a non-invasive imaging modality that measures lipofuscin that has accumulated in the retinal pigment epithelium (RPE). Excessive lipofuscin in the RPE is a common pathway found in several diseases including Stargardt’s disease and age-related macular degeneration. This review discusses the role of photooxidative damage in the development of lipofuscin and the principles of fundus autofluorescence.     

两种波长自发荧光联合频域光学相干断层扫描对视网膜色素变性微结构与功能的再认识

目的 分析视网膜色素变性(RP)中两种波长眼底自发荧光(FAF)和多焦视网膜电图(mf-ERG)的临床特征,应用频域光学相干断层扫描(Spectralis OCT)观察相应的视网膜微结构改变,进一步探讨两者联合应用在RP诊断中的价值.方法 非干预性、观察性研究.应用激光共焦扫描检眼镜(德国Heidelberg公司)对8例(15眼)RP患者进行蓝光自发荧光(BL-FAF,激发光488 nm,滤光片＞500 nm)、近红外波长自发荧光(NIR-FAF,激发光787 nm,滤光片＞800 nm)及Spectralis OCT检查.5例进行了荧光素眼底血管造影(FFA)检查,其中3例同时接受了吲哚青绿血管造影(ICGA)检查;7例进行了眼底照相;4例患者接受了mf-ERG检查.分析RP病例FAF分布特征及Spectralis OCT所示视网膜微结构与mf-ERG中反应振幅密度的对应改变.结果 在视网膜色素上皮(RPE)和光感受器(PR)萎缩及骨细胞沉着部位,BL-FAF与NIR-FAF均为低荧光,mf-ERG反应强度降低,中心反应区正常尖峰消失.正常FAF区域内Spectralis OCT提示视网膜PR、RPE保存完整,外界膜(OLM)部分断裂.部分病例NIR-FAF高荧光区域小于BL-FAF.FFA早期出现典型的"窗样缺损"现象,提示RPE受损:早期ICGA表现为脉络膜毛细血管萎缩.结论 两种波长FAF联合Spectralis OCT及mf-ERG是诊断RP十分有用的非侵入性工具,其特征性改变提示PR和RPE细胞拥有共同的退化途径,而BL-FAF和NIR-FAF提示该途径所累及的脂褐索和非脂褐素的荧光性物质分别存在不同的病理生理变化.     

七种眼底形态的红外线扫描和自发荧光图像的分析

目的解析7种眼底形态的红外线（IR）扫描和自发荧光图像（AF）。方法使用Heidelberg公司HRA-Spectralis眼底检查系统,对537例患者（1023只眼）进行眼底IR和AF检查。结果从中选出8例（8只眼）具有典型特征的眼底图像。结论IR分辨率较一般眼底照相高,可用于眼底浅层疾病的检查诊断;AF在诊断视网膜色素上皮（RPE）病变上有无可比拟的优势,它反映的是RPE代谢的变化,且视网膜色素变性（RP）患者的AF图像有极其明显的特征,是检查诊断RP病的金指标。     

Macular autofluorescence in eyes with cystoid macula edema,detected with 488 nm-excitation but not with 580 nm-excitation

Background  Fundus autofluorescence (AF) derives from lipofuscin in the retinal pigment epithelium (RPE). Because lipofuscin is a by-product of phagocytosis of photoreceptors by RPE, AF imaging is expected to describe some functional aspect of the retina. In this study we report distribution of AF in patients showing macular edema. Methods  Three eyes with diabetic macular edema (DME) and 11 with retinal vein occlusion (RVO), associated with macular edema (ME) were examined. ME was determined by standard fundus examination, fluorescein angiography (FA) and optical coherence tomography (OCT). AF was recorded using a Heidelberg confocal scanning laser ophthalmoscope (cSLO) with 488 nm laser exciter (488 nm-AF), and a conventional Topcon fundus camera with halogen lamp exciter and 580 nm band-pass filter (580 nm-AF). Color fundus picture, FA image and these two AF images were analyzed by superimposing all images. Results  All subjects presented cystoid macular edema (CME) with petaloid pattern hyperfluorescence in FA. In 488 nm-AF, all eyes (100%) showed macular autofluorescence of a similar shape to that of the CME in FA. In contrast, in 580 nm-AF only one eye (7%) presented this corresponding petaloid-shaped autofluorescence. In all cases, peripheral retinal edemas did not show autofluorescence corresponding to the leakage in FA. Conclusions  In eyes with CME, analogous hyperautofluorescence to the CME was always observed in 488 nm-AF, while it was rarely observed in 580 nm-AF. Moreover, this CME hyperautofluorescence was only seen in the macular area. We hypothesize that autofluorescence from CME may be considered as a “pseudo” or “relative” autofluorescence, due to macular stretching following CME that may result in lateral displacement of macular pigments (MPs) and subsequent reduction of MPs density, as MPs block 488 nm-AF more intensely than 580 nm-AF. Although this phenomenon may not directly indicate change of RPE function, it may be used as a method to assess or track CME non-invasively. No author has financial relationship for this research. Kenichiro Bessho and Fumi Gomi have full control of all primary data. The authors agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data upon request.     

Distribution of pigment epithelium autofluorescence in retinal disease state recorded in vivo and its change over time

· Background: Recently a technique of imaging the retinal pigment epithelium (RPE) has been developed that takes advantages of its intrinsic fluorescence derived from lipofuscin. The purpose of this study was to document the distribution of fundus autofluorescence in patients with various retinal diseases and its change over time. · Methods: The intensity and spatial distribution of fundus autofluorescence was documented in 318 eyes from 159 patients with various retinal diseases using a confocal Laser Scanning Ophthalmoscope. Thirty patients with macular dystrophies and 30 with age-related macular disease underwent serial examinations over a period of 1–3 years in order to monitor the changes over time of fundus autofluorescence. · Results: Absent autofluorescence corresponded well spatially with outer retinal atrophy in eyes with retinitis pigmentosa and rod-cone dystrophy. Abnormally high background autofluorescence was seen in the macular region in some patients with dominant and recessive retinitis pigmentosa and rod-cone dystrophies. In areas of macular edema fundus autofluorescence was abnormal. Fundus autofluorescence showed changes over time in most of the eyes with retinal diseases studied. · Conclusion: Fundus autofluorescence allows documentation of areas of photoreceptor cell loss in eyes with retinitis pigmentosa and rod-cone dystrophies. If abnormal high background autofluorescence in the surviving areas occurs only in some patients with retinitis pigmentosa, the technique may serve to distinguish the regional from the diffuse type of disease. Over time, fundus autofluorescence may demonstrate change or may remain stable. Received: 14 August 1997 Revised version received: 28 January 1998 Accepted: 4 March 1998     

ABCA4-associated retinal degenerations spare structure and function of the human parapapillary retina

PURPOSE: To study the parapapillary retinal region in patients with ABCA4-associated retinal degenerations. METHODS: Patients with Stargardt disease or cone-rod dystrophy and disease-causing variants in the ABCA4 gene were included. Fixation location was determined under fundus visualization, and central cone-mediated vision was measured. Intensity and texture abnormalities of autofluorescence (AF) images were quantified. Parapapillary retina of an eye donor with ungenotyped Stargardt disease was examined microscopically. RESULTS: AF images ranged from normal, to spatially homogenous abnormal increase of intensity, to a spatially heterogenous speckled pattern, to variably sized patches of low intensity. A parapapillary ring of normal-appearing AF was visible at all disease stages. Quantitative analysis of the intensity and texture properties of AF images showed the preserved region to be an annulus, at least 0.6 mm wide, surrounding the optic nerve head. A similar region of relatively preserved photoreceptor nuclei was apparent in the donor retina. In patients with foveal fixation, there was better cone sensitivity at a parapapillary locus in the nasal retina than at the same eccentricity in the temporal retina. In patients with eccentric fixation, approximately 30% had a preferred retinal locus in the parapapillary retina. CONCLUSIONS: Human retinal degenerations caused by ABCA4 mutations spare the structure of retina and RPE in a circular parapapillary region that commonly serves as the preferred fixation locus when central vision is lost. The retina between fovea and optic nerve head could serve as a convenient, accessible, and informative region for structural and functional studies to determine natural history or outcome of therapy in ABCA4-associated disease.     

Multi-modality imaging on multiple evanescent white dot syndrome-A Spectralis Study

AIM: To present retinal microstructure, metabolism and function abnormalities in the course of multiple evanescent white dot syndrome (MEWDS) by Heidelberg spectralis modality imaging platform and observe its outcome by EDI-SD-OCT and two wavelength autofluorescence.METHODS: A case of multiple evanescent white dot syndrome in a 23-year-old female presented initially with a 15-day history of floaters and a central scotoma in the right eye. To establish the diagnosis, multimodality imaging was performed, namely, blue light-fundus autofluorescence (BL-FAF, excitation 488nm, emission >500nm), near-infrared fundus autofluorescence (NIR-FAF, excitation 787nm, emission >800nm) using a confocal scanning laser ophthalmoscope, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), spectrum-domain enhance depth imaging optical coherence tomography (SD-EDI-OCT), multifocal electroretinography (mf-ERG) and fundus photogragh were performed and followed up at the eighth month after initially visiting.RESULTS: Optical coherence tomography(OCT) showed a transient disruption of the foveal photoreceptor outer segments in correspondence to foveal granularity. NIR-FAF showed hypoautofluorescent areas, ≤40μm in size, mostly concentrated around the posterior pole and its temporal side less than that in BL-FAF. Mf-ERG show pinnacle disappeared in fovea and macula and responses decreased markedly compared with the follow eye. At the eighth month follow up, hyperfluorescence in BL-FAF were disappear, while, NIR-FAF Hypofluorescent spots in early stage of such lesion were reduced. But OCT demonstrated the structure was recovered in residual Hypofluorescent area in NIR-FAF. The subfoveal choroidal thickness was decreased from 372μm to 307μm slightly and cost line was recovered.CONCLUSION: MEWDS is a benign self-healing disease and there is no pathological evidence to investigate the natural course of such disease. SD-OCT allows highly detailed images approaching histopathology to certify the microstructural changes. Two-wave length FAF and mf-ERG provide more information about metabolism in outer retina especial RPE and photoreceptor. Spectralis OCT combined with two-wavelength FAF and mf-ERG provide a new way to analyze this disease and offer more details for therapy and follow-up.