Fundus Autofluorescence Patterns Research Articles

The Value of Combining Autofluorescence and Optical Coherence Tomography in Predicting the Visual Prognosis of Sealed Macular Holes

To investigate the autofluorescence patterns of sealed macular holes and determine the correlations of the postoperative changes in spectral-domain optical coherence tomography and fundus autofluorescence (FAF) with the best-corrected visual acuity (BCVA) of patients with sealed idiopathic macular holes. Retrospective consecutive observational case series. Seventy-seven eyes from 75 consecutive patients who had undergone successful vitrectomies for idiopathic macular holes by a single surgeon with postoperative follow-ups for over 1 year were included. FAF imaging studies were performed 1month and 6months post surgery, and optical coherence tomography (OCT) was performed at regular intervals after surgery. The main outcome measures were macular hole size, FAF patterns, retina outer segment from OCT, and BCVA before and after operation. The patients who had intact external limiting membranes (ELMs) at 1month after surgery had better BCVAs than those without (P < .001), regardless of the photoreceptor inner segment/outer segment (IS/OS) condition. The FAF patterns were divided into 3 groups: homogenous hyperfluorescence, patchy hyperfluorescence, and normal hypofluorescence. No significant BCVA differences were noted (P= .28) among the 3 groups. However, significantly better BCVAs were noted in the patients who had both intact ELMs and normal hypofluorescence patterns (P= .011). In sealed macular holes, intact ELMs predicted good postoperative BCVA. In this subgroup, a hypofluorescence pattern on the FAF imaging predicted the best postoperative BCVA.

Wide-Field Fundus Autofluorescence Imaging of Retinitis Pigmentosa

To evaluate the clinical usefulness of wide-field fundus autofluorescence (FAF) imaging in patients with retinitis pigmentosa (RP). Cross-sectional case series. Seventy-five eyes of 75 patients with RP. We examined the eyes of the RP patients using the Optos 200Tx imaging system (Optos PLC, Dunfermline, United Kingdom) and identified abnormal FAF patterns such as ring hyperautofluorescence and patchy hypoautofluorescent areas. Patients with hyperautofluorescent rings or foveal hyperautofluorescence were compared with those without such findings. We determined the percentage area occupied by the FAF abnormalities within a defined region of the eye and examined the relationship between the percentage area of these abnormalities and the visual field area. Moreover, we categorized the patients into 3 different groups based on the presence of a patchy hypoautofluorescent lesion larger than 1 disc diameter: Group A consisted of those with patchy lesions smaller than 1 disc diameter, group B consisted of those with patchy lesions larger than 1 disc diameter but present in only 1 quadrant, and group C consisted of those with patchy lesions larger than 1 disc diameter and present in more than 1 quadrant. In addition, various clinical characteristics were compared among these 3 groups. Predicting the visual field size and duration of the disease in RP patients based on FAF patterns. Patients without hyperautofluorescent rings or foveal hyperautofluorescence had better visual acuity or mean deviation measured with a Humphrey perimeter. The total area of the abnormal FAF image correlated with the visual field area measured with a Goldmann perimeter (R = -0.64, P<0.001). The individuals with the large patchy hypofluorescent areas (i.e., larger than 1 disc diameter) were older than those with small patchy hypofluorescent areas (group A vs. groups B and C, P = 0.002 and P<0.001, respectively) and had experienced the symptoms for longer durations (group A vs. groups B and C, P<0.05 and P<0.001, respectively). We can estimate the visual field in patients with RP using the objective measurements from wide-field FAF. The presence of patchy hypofluorescent lesions can be used an indicator of the duration of RP. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Peripheral Autofluorescence and Clinical Findings in Neovascular and Non-neovascular Age-related Macular Degeneration

To characterize peripheral fundus autofluorescence (FAF) abnormalities in patients with age-related macular degeneration (AMD), correlate these with clinical findings, and identify risk factors associated with these FAF abnormalities. Clinic-based, cross-sectional study. A total of 119 consecutive patients: 100 patients with AMD (200 eyes) and 19 patients without AMD (38 eyes). In a prospective study performed at the Doheny Eye Institute, University of Southern California, widefield 200-degree FAF and color images were obtained by the Optos 200Tx Ultra-Widefield device (Optos, Dunfermline, Scotland) using a standardized imaging protocol. The FAF images were captured centered on the fovea, and additional images were captured after steering the field of view inferiorly and superiorly. All FAF and color images were graded independently by 2 masked ophthalmologists with respect to the presence, location, extent, and type of peripheral (defined as outside the central 30 degrees) FAF abnormality. Presence and type of peripheral FAF abnormalities. Peripheral FAF abnormalities were evident in 164 eyes (68.9%), with several distinct FAF patterns identified: granular (46.2%), mottled (34.0%), and nummular (18.1%). A 90% concordance of FAF patterns was observed between both eyes. Abnormal FAF occurred more frequently in neovascular compared with non-neovascular AMD or normal eyes (86% vs. 72.8% vs. 18.4%, respectively, P<0.001). Significant risk factors for peripheral FAF abnormalities were AMD type (neovascular AMD odds ratio [OR], 12.7 and non-neovascular AMD OR, 6.2 compared with normal eyes, P<0.001), older age (OR, 6.5; 95% confidence interval [CI], 2.4-17.8; P<0.001 for the oldest quartile compared with the youngest), and female sex (OR, 4.1; 95% CI, 1.9-8.9; P<0.001). Clinical features on color photography were detected in 174 eyes (73.1%): peripheral drusen (51.7%), retinal pigment epithelium (RPE) depigmentation (34.9%), RPE hyperpigmentation (branching reticular pigmentation) (22.7%), and atrophic patches (16.8%). There was a high correlation between specific FAF and clinical findings: granular FAF with peripheral drusen (P<0.001) and mottled FAF with RPE depigmentation (P<0.001). Several distinct patterns of peripheral FAF abnormalities were observed in 68.9% of patients, with AMD type, female sex, and age being independent risk factors. The peripheral FAF patterns correlate strongly with specific clinical features seen in eyes with AMD. Proprietary or commercial disclosure may be found after the references.

Green-light fundus autofluorescence in diabetic macular edema.

To evaluate the role of central green-light fundus autofluorescence (FAF) in diabetic macular edema (DME). A consecutive series of 92 study eyes with diabetic retinopathy were included. Out of those, 51 diabetic eyes had DME and were compared to 41 diabetic eyes without DME. In all subjects, green-light FAF images were obtained, quantified and classified into various FAF patterns. Cross-sectional optical coherence tomography (OCT) scans were obtained for evaluation of Inner/Outer segment (IS/OS) layer integrity, measurements of central RPE-IS/OS layer thickness as well as classification of DME into various subtypes. Mean central green-light FAF intensity of eyes with DME (1.289±0.140)log did not significantly differ from diabetic patients without DME (1.317±0.137)log. Most classifiable FAF patterns were seen in patients with cystoid DME. Mean central retinal thickness (CRT) of all study eyes with DME was (501.9±112.4)µm compared to (328.2±27.0)µm in diabetic patients without DME. Patients with DME had significantly more disrupted photoreceptor IS/OS layers than diabetic patients without DME (28/51 vs 5/41, P<0.001). Mean RPE-IS/OS thickness of patients with DME (60.7±14.1)µm was significantly (P<0.001) lower than in diabetic eyes without DME (73.5±9.4)µm. Correlation analys1s revealed non-significant correlations of green-light FAF intensity and OCT parameters in all subtypes of DME. Our results indicate a poor correlation of central green-light FAF intensity with CRT, IS/OS layer integrity or RPE-IS/OS layer thickness in diabetic patients with or without DME and its various subtypes. Thus, central green-light FAF is not suitable for detection of retinal thickening in DME.

Histologic Basis of Variations in Retinal Pigment Epithelium Autofluorescence in Eyes with Geographic Atrophy

Lipofuscin contained in the retinal pigment epithelium (RPE) is the main source of fundus autofluorescence (FAF), the target of an imaging method useful for estimating the progression of geographic atrophy (GA) in clinical trials. To establish a cellular basis for hyperfluorescent GA border zones, histologic autofluorescence (HAF) was measured at defined stages of RPE pathologic progression. Experimental study. Ten GA donor eyes (mean age ± standard deviation, 87.1 ± 4.0 years) and 3 age-matched control eyes (mean age ± standard deviation, 84.0 ± 7.2 years) without GA. The 10-micrometer-thick sections were divided into zones of RPE morphologic features according to an 8-point scale. Any HAF excited by 488 nm light was imaged by laser confocal microscopy. The HAF intensity summed along vertical lines perpendicular to Bruch's membrane at 0.2-μm intervals served as a surrogate for FAF. Intensity profiles in 151 zones were normalized to grade 0 at a standard reference location in each eye. Cross-sectional area, mean, and sum autofluorescence for individual RPE cells were measured (cellular autofluorescence [CAF]). Statistically significant differences in intensity and localization of HAF and CAF at defined stages of RPE morphologic progression for GA and control eyes. The RPE morphologic features were most abnormal (cell rounding, sloughing, and layering; grade 2) and HAF intensity profiles were highest and most variable immediately adjacent to atrophic areas. Peaks in HAF intensity frequently were associated with vertically superimposed cells. The HAF value that optimally separated reactive RPE was 0.66 standard deviations more than the mean for uninvolved RPE and was associated with a sensitivity of 75.8% and a specificity of 76.3%. When variable cell area was accounted for, neither mean nor sum CAF differed significantly among the RPE pathologic grades. Areas with advanced RPE alterations are most likely to exhibit clinically recognizable patterns of elevated FAF around GA, but may not predict cells about to die, because of vertically superimposed cells and cellular fragments. These data do not support a role for lipofuscin-related cell death and call into question the rationale of treatments targeting lipofuscin.

Hyperautofluorescent ring in eyes with macular holes

BackgroundFundus autofluorescence studies in eyes with macular holes (MHs) have shown a hyperautofluorescent spot corresponding to the hole and a hypoautofluorescent ring corresponding to the fluid cuff surrounding the hole. The purpose of this report is to present three cases of MH with a different fundus autofluorescence pattern.Case reportsCase 1 was a 62-year-old woman who did not know the duration of the MH in her left eye. Her decimal best-corrected visual acuity (BCVA) was 0.08. The left eye had a one-half disc diameter MH with a depigmented ring surrounding the area of the fluid cuff. Fundus autofluorescence showed a hyperautofluorescent ring corresponding to the depigmented ring. After vitrectomy, fundus autofluorescence showed the same size hyperautofluorescent ring despite the decreased size of the opened MH. Case 2 was a 69-year-old woman who had been diagnosed with MH in the right eye 13 years earlier. Her decimal BCVA was 0.1. The right eye had a one-half disc diameter MH with a depigmented ring surrounding the area of the fluid cuff. Fundus autofluorescence showed a hyperautofluorescent ring corresponding to the depigmented ring. Postoperative fundus autofluorescence showed the same size hyperautofluorescent ring despite the hole being closed. The decimal BCVA was 0.2 in her right eye 6 months after vitrectomy. Case 3 was a 71-year-old woman who had been diagnosed with MH in the right eye 15 years earlier. Her decimal BCVA was 0.1. The right eye had a one-half disc diameter MH with a depigmented ring which corresponded with a hyperautofluorescent ring. Postoperative fundus autofluorescence showed the same size hyperautofluorescent ring despite the hole being closed. The decimal BCVA was 0.2 in her right eye 6 months after vitrectomy.ConclusionOur findings suggest that a hyperautofluorescent ring in eyes with MHs may be an indicator of a poor surgical prognosis both anatomically and functionally.

Comparison between fundus autofluorescence images and color fundus photos in patients with late dry age-related macular degeneration

Purpose: The purpose was to compare between color fundus photography (CFP) images and fundus autofluorescence (FAF) images of cases with geographical atrophy (GA) about size. To evaluate the relation between different phenotypes of FAF changes and best corrected visual acuity (BCVA) in cases with late dry age-related macular degeneration (AMD) (GA). Materials and Methods: This study was conducted on 18 eyes of 18 patients aged 55 years. Patients unwilling to participate in the study, suffering from hereditary fundus diseases, had previous laser photocoagulation treatment for any cause, were excluded. BCVA using Snellen chart was measured. Retinal imaging including CFP with 50° field camera: Topcon TRC-50 IX - and FAF using spectralis Heidelberg retinal angiograph (HRA) + optical coherence tomography (HRA, Heidelberg Engineering, Germany) were done. All images were optimized and then manually measured using image analysis software (Adobe Photoshop version CS6; Inc., San Jose, California, USA). Images of fundus autofluorescence in cases of late dry AMD were classified to phenotypes at the junctional zone according to the classification of abnormal FAF patterns. Results: According to sex distribution, 33.3% (6 eyes) were males and 66.7% (12 eyes) were females . The mean age of the study participants was 72.89 ± 9.09 years. About surface area of GA, the mean surface area of GA by FAF was 71094.56 ± 21490.53 pixels and by color fundus camera were 46236.56 ± 13153.46 pixels. About FAF phenotypes in late dry AMD cases, Twelve eyes (66.7%) had diffuse pattern, 11.1% (2 eyes) had a none pattern (no specific pattern), and 22.2% (4 eyes) had focal pattern. Color fundus camera underestimated the surface area of GA in cases of late dry AMD. BCVA was best in cases with no specific pattern of autofluorescence at the junctional zone of the GA, followed by cases with focal pattern of hyperautofluorescence while cases with diffuse increases of autofluorescence at the junctional zone showed the worst VA. Conclusions: CFP underestimated the size of the GA, as compared with FAF measured sizes. BCVA was best in cases with no specific pattern of autofluorescence at the junctional zone of the GA, followed by cases with focal pattern of hyperautofluorescence while cases with diffuse increases of autofluorescence at the junctional zone showed the worst VA.

Optical Coherence Tomographic Imaging of Sub-Retinal Pigment Epithelium Lipid

OBJECTIVE To describe an optical coherence tomographic finding of layered hyperreflective bands beneath the retinal pigment epithelium (RPE), the so-called onion sign believed to represent lipid within a vascularized pigment epithelial detachment. METHODS This retrospective observational case series involved reviewing clinical histories of patients with the onion sign. Imaging studies analyzed included spectral-domain optical coherence tomography, color and red-free photographs, near infrared reflectance, fundus autofluorescence, and blue-light fundus autofluorescence. RESULTS A total of 22 eyes of 20 patients with sub-RPE hyperreflective bands were identified. There were 15 women and 5 men with a mean patient age of 76 years (range, 60-92 years). Snellen best-corrected visual acuities ranged from 20/25 to counting fingers, with a median of 20/80. Two patients had bilateral involvement, and 3 of 17 eyes had multifocal onion signs in the same eye. All eyes had neovascular age-related macular degeneration, with type 1 (sub-RPE) neovascularization. In all patients, the onion sign correlated with areas of yellow-gray exudates seen clinically that appeared bright on red-free and near infrared reflectance imaging. No specific fundus autofluorescence or blue-light fundus autofluorescence pattern was identified. CONCLUSIONS The onion sign refers to layered hyperreflective bands in the sub-RPE space usually associated with chronic exudation from type 1 neovascularization in patients with age-related macular degeneration. With an associated bright near infrared reflectance, these bands may correspond to lipid, collagen, or fibrin. Because the onion sign colocalizes to areas of exudation that are known to consist of lipoprotein, we propose that this finding may represent layers of precipitated lipid in the sub-RPE space. To our knowledge, this is the first report of lipid detected in the sub-RPE space on clinical examination.

Fundus Autofluorescence Patterns in Stargardt Disease Over Time

Fundus Autofluorescence Patterns in Stargardt Disease Over Time

Fundus Autofluorescence in Polypoidal Choroidal Vasculopathy

To investigate and compare the characteristics of fundus autofluorescence (FAF) in polypoidal choroidal vasculopathy (PCV) with those in typical neovascular age-related macular degeneration (AMD). Retrospective, observational, consecutive case series. Ninety-two patients with PCV (92 affected eyes and 86 unaffected fellow eyes) and 31 patients with typical neovascular occult AMD with no classic choroidal neovascularization (31 affected eyes and 24 unaffected fellow eyes). All study eyes underwent FAF photography with a fundus camera-based system. The incidence and distribution of hypoautofluorescence, that is, the manifestation of retinal pigment epithelium (RPE) damages, were evaluated. The characteristic FAF findings in PCV. In the affected eyes with PCV, the sites of the neovascular lesions showed 2 distinct FAF patterns: (1) the confluent hypoautofluorescence at the polypoidal lesions and (2) the granular hypoautofluorescence at the branching choroidal vascular networks. The confluent hypoautofluorescence, most of which was surrounded by a hyperautofluorescent ring, was seen in 74 eyes (80.4%) with PCV but was seen in no eyes with typical neovascular AMD (P < 0.001). The granular hypoautofluorescence was seen in 91 eyes (98.9%) with PCV and 27 eyes (87.1%) with typical neovascular AMD (P = 0.014). In addition, the eyes with PCV more frequently showed hypoautofluorescence outside the macular area than those with typical neovascular AMD (P = 0.021). In the unaffected fellow eyes, the hypoautofluorescence was more frequently observed in patients with PCV than in those with typical neovascular AMD, inside the macular area and in the entire FAF image (P = 0.012, P = 0.003, respectively). In eyes with PCV, the polypoidal lesions and the branching choroidal vascular networks appeared to affect the RPE and induce peculiar FAF findings. When compared with the patients with typical neovascular AMD, widespread RPE damage was more frequently observed in the patients with PCV, both in the affected eyes and in the unaffected fellow eyes.

Abnormal Fundus Autofluorescence Results of Patients in Long-term Treatment with Deferoxamine

To describe and classify patterns of abnormal fundus autofluorescence (FAF) of patients with β-thalassemia receiving long-term treatment with deferoxamine (DFO). Prospective, cross-sectional, case-control study. A total of 197 consecutive patients with β-thalassemia major or intermedia with at least 10 years of treatment with DFO were recruited in a tertiary referral center in Milan, Italy, and were investigated. Seventy-nine thalassemic patients without a history of chelation therapy were included as a control group. All of the patients were investigated using best-corrected visual acuity (BCVA), fundus photography, and FAF imaging by confocal scanning laser ophthalmoscopy (cSLO) and were compared with the control group. Identification of abnormal FAF patterns in thalassemic patients treated with long-term DFO and their progression and relationship with visual function. Abnormal FAF not related to other diseases was observed in 18 of the 197 patients (9%) and was classified into 4 phenotypic patterns: minimal change, focal, patchy, and speckled. The abnormal increased or decreased FAF was bilateral in all the cases, and only in some cases did it correspond to funduscopically visible alterations. There were no FAF abnormalities in the control group. During the follow-up, progressive FAF changes related to retinal pigment epithelium (RPE) damage occurred in the patchy pattern, associated with decreasing BCVA. Patients with speckled and focal patterns showed limited or no changes in FAF during the follow-up. No changes in FAF were found in patients with a minimal change pattern. No treated patient with a normal baseline examination demonstrated FAF changes. Patients with patterns other than the minimal change showed significant BCVA deterioration (P<0.001). Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Fundus autofluorescence is a helpful, fast, and noninvasive tool for monitoring the status of the macula in patients at risk of DFO toxicity. It may be useful in the decision to discontinue or switch the therapy in cases of particular high risk for disease progression. The progressive alteration of the RPE suggests an important role of pathologic RPE changes in the evolution of visual loss during long-term treatment with DFO.

FUNDUS AUTOFLUORESCENCE IN SERPIGINOUSLIKE CHOROIDITIS

To report the fundus autofluorescence characteristics in serpiginouslike choroiditis. Twenty-nine patients with presumed tubercular serpiginouslike choroiditis between November 2008 and January 2010 underwent fundus autofluorescence imaging during the acute stage and at regular intervals till the lesions healed. All patients received antitubercular therapy with oral corticosteroids. The autofluorescence images were compared with color fundus photography and fundus fluorescein angiography. The main outcome measure was fundus autofluorescence characteristics of lesions during the course of the disease. The pattern of fundus autofluorescence changed as the lesions evolved from the acute to the healed stage. In acute stage, the lesions showed an ill-defined halo of increased autofluorescence (hyperautofluorescence), giving it a diffuse, amorphous appearance (Stage I, acute). As the lesions began to heal, a thin rim of decreased autofluorescence (hypoautofluorescence) surrounded the lesion, defining its edges. The lesions showed predominantly hyperautofluorescence with stippled pattern (Stage II, subacute). With further healing, the hypoautofluorescence progressed and the lesion appeared predominantly hypoautofluorescent with stippled pattern (Stage III, nearly resolved). On complete healing, the lesions became uniformly hypoautofluorescent (Stage IV, completely resolved). Fundus autofluorescence highlighted the areas of disease activity and was a quick imaging tool for monitoring the course of lesions in serpiginouslike choroiditis.

Microperimetric Correlations of Autofluorescence and Optical Coherence Tomography Imaging in Dry Age-Related Macular Degeneration

To investigate the microperimetric correlations of autofluorescence imaging and optical coherence tomography (OCT) in dry age-related macular degeneration (AMD). Retrospective, observational, cross-sectional study. Consecutive patients with dry AMD underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), blue fundus autofluorescence (FAF), near-infrared autofluorescence, and spectral-domain (SD)-OCT with integrated microperimetry. A total of 58 eyes of 29 patients (21 women; mean age 73 ± 9 years) were included. Mean BCVA was 0.28 ± 0.3 logarithm of the minimal angle of resolution (logMAR). Overall, 2842 points were analyzed as regards FAF and near-infrared autofluorescence patterns, the status of inner segment/outer segment (IS/OS) interface, and retinal sensitivity. We observed a good correlation between the FAF and near-infrared autofluorescence patterns for all the points graded (increased FAF/near-infrared autofluorescence, Pearson rho = 0.6, P = .02; decreased FAF/near-infrared autofluorescence, Pearson rho = 0.7, P = .01; normal FAF/near-infrared autofluorescence, Pearson rho = 0.7, P = .01). Mean retinal sensitivity was significantly reduced in cases of decreased FAF (4.73 ± 2.23 dB) or increased FAF (4.75 ± 2.39 dB) compared with normal FAF (7.44 ± 2.34 dB) (P = .001). Mean retinal sensitivity was significantly reduced in case of decreased near-infrared autofluorescence (3.87 ± 2.28 dB), compared with increased near-infrared autofluorescence (5.76 ± 2.44 dB) (P = .02); mean retinal sensitivity in case of increased near-infrared autofluorescence was significantly reduced compared with normal near-infrared autofluorescence (7.15 ± 2.38 dB) (P = .002). On SD-OCT, there was a high inverse correlation between retinal sensitivity and rate of disruptions in IS/OS interface (Pearson rho = -0.72, P = .001). A reduced retinal sensitivity consistently correlates with decreased FAF/near-infrared autofluorescence and a disrupted IS/OS interface. Increased near-infrared autofluorescence may represent a useful method for detection of retinal abnormalities early in dry AMD development.

Blue-Light versus Green-Light Autofluorescence: Lesion Size of Areas of Geographic Atrophy

Blue-light fundus autofluorescence (FAF) imaging is currently widely used for assessing dry age-related macular degeneration (ARMD). However, at this wavelength, the fovea appears as circular zone of marked hypofluorescence, due to the absorption of macular pigment (MP). This dark spot could be misinterpreted as an atrophic area and could lead to difficulties in identifying small, central changes. The purpose of the study was to analyze differences in image quality, FAF patterns, and lesion size, when using conventional blue-light (Λ(1) = 488 nm) and green-light (Λ(2) = 514 nm) FAF. Patients older than 50 years with central areas of geographic atrophy (GA) secondary to ARMD were enrolled. Images were recorded with a modified confocal scanning laser ophthalmoscope (cSLO). Image quality and patterns were analyzed. The quantification of the GA was performed with customized image-analysis software. In total, 95 eyes were included. The borders of the central atrophic patches and the boundaries of the preserved foveal island were better identified in 514-nm images. In both excitation wavelengths the signal-to-noise ratio was sufficient for the identification of the FAF pattern. Significant differences were observed in the size of the GA areas detected in the 488- and 514-nm wavelength images (4.29 ± 3.76 mm(2) vs. 3.80 ± 3.68 mm(2); P < 0.001). The green-light FAF images (514 nm) are superior for the accurate analysis of small, central, pathologic changes, and for the determination of the central GA lesion size. Using only blue-light FAF could lead to an overinterpretation of the size of atrophic patches and the center involvement, because it suggests the presence of atrophy in the fovea.

Intra and interobserver agreement in the classification of fundus autofluorescence patterns in geographic atrophy secondary to age-related macular degeneration

To describe the intra and interobserver agreement in the evaluation of fundus autofluorescence patterns in geographic atrophy secondary to age-related macular degeneration. A consecutive series of patients with geographic atrophy and fundus autofluorescence images of a minimum acceptable quality for grading were included. Four observers with experience in the evaluation of autofluorescence images independently classified the randomly presented series of images on two occasions, at least 1month apart from each other (intraobserver analysis). The second determination of each observer was used for evaluation of interobserver agreement. The kappa statistic and 95% confidence intervals, together with percentages of agreement, were used to analyze the results. The final sample included 69 eyes of 49 patients. Intraobserver agreement ranged from substantial to almost perfect (kappa between 0.51 and 0.83), while interobserver results ranged from poor to substantial (corresponding to kappa between 0.30 and 0.62). The use of more simple classifications improved reproducibility. Although intraobserver reproducibility was high, interobserver agreement was variable. Clear descriptions and a uniform set of criteria to classify these patients are needed if fundus autofluorescence imaging is used to evaluate patients with geographic atrophy.

Centrifugal Expansion of Fundus Autofluorescence Patterns in Stargardt Disease Over Time

To study the longitudinal changes in autofluorescence in Stargardt disease to reveal aspects of disease progression not previously evident. Changes in autofluorescence reflect changing fluorophore compositions of lipofuscin and melanin in retinal pigment epithelial cells, which has been hypothesized to contribute to Stargardt disease pathogenesis. We examined the temporospatial patterns of fundus autofluorescence with excitation at both 488 nm (standard fundus autofluorescence) and 795 nm (near-infrared autofluorescence) in a longitudinal case series involving 8 eyes of 4 patients (range of follow-up, 11-57 months; mean, 39 months). Image processing was performed to analyze spatial and temporal cross-modality associations. Longitudinal fundus autofluorescence imaging of fleck lesions revealed hyperautofluorescent lesions that extended in a centrifugal direction from the fovea with time. Patterns of spread were nonrandom and followed a radial path that left behind a trail of diminishing autofluorescence. Longitudinal near-infrared autofluorescence imaging also demonstrated centrifugal lesion spread but with fewer hyperautofluorescent lesions, suggestive of more transient hyperautofluorescence and more rapid decay at longer wavelengths. Fundus autofluorescence and near-infrared autofluorescence abnormalities were spatially correlated with each other, and together they reflect systematic progressions in fleck distribution and fluorophore composition occurring during the natural history of the disease. Stargardt disease fleck lesions do not evolve randomly in location but instead follow consistent patterns of radial expansion and a systematic decay of autofluorescence that reflect changing lipofuscin and melanin compositions in retinal pigment epithelial cells. These progressive foveal-to-peripheral changes are helpful in elucidating molecular and cellular mechanisms underlying Stargardt disease and may constitute potential outcome measures in clinical trials.

Fundus autofluorescence and retinal structure as determined by spectral domain optical coherence tomography, and retinal function in retinitis pigmentosa

To investigate the association between fundus autofluorescence (FAF) and retinal structure and function in retinitis pigmentosa (RP). For image acquisition, HRA2 (Heidelberg Engineering) and 3D-OCT1000 (Topcon Corp.) were used. Based on FAF examination, 88 eyes of 44 RP patients were categorized into three types. The area within the hyperautofluorescent ring and the area of preserved retinal autofluorescence with FAF was calculated. The association between the pattern of FAF and the residual area of the junction between the inner and outer segments of the photoreceptors (IS/OS line), and the relationship between the area within hyperautofluorescent ring, the area of preserved retinal autofluorescence and the mean deviation (MD) of static perimetry were assessed. Twenty-four eyes were with preserved retinal autofluorescence without hyperautofluorescent ring, 54 eyes were with hyperautofluorescent ring and ten eyes were with abnormal foveal autofluorescence both in the fovea and the periphery of the 30° scan. In the first type, the IS/OS line was clearly detected. In the second type, the residual area of the partially distinct IS/OS line corresponded with the area within hyperautofluorescent ring with significant correlation between the area within hyperautofluorescent ring and the MD (R(2) = 0.705, p < 0.001); however, there was no correlation between the area of preserved retinal autofluorescence and the MD, or between the area of preserved retinal autofluorescence and the area within hyperautofluorescent ring. In the third type, the IS/OS line was completely absent. The residual IS/OS line can be found in the area inside the hyperautofluorescent ring and correlates with residual visual function.

Fundus autofluorescence in acute and chronic central serous chorioretinopathy

Background: A prospective evaluation of the pattern of fundus autofluorescence in cases of acute versus chronic central serous chorioretinopathy (CSR).Methods: A prospective, cross‐sectional, single‐centre investigation was performed using three diagnostic techniques, namely, fundus autofluorescence, optical coherence tomography and fundus fluorescein angiography to evaluate a sample of patients (n = 42 eyes) with both acute (n = 25 eyes) and chronic (n = 17 eyes) CSR.Results: Hypoautofluoresecence was found in 80 per cent (20 eyes) and 88.2 per cent (15 eyes) of eyes in the acute and chronic central serous chorioretinopathy groups, respectively, corresponding to the leakage points depicted by fluorescein angiography. Hypoautofluoresence corresponding to the areas of subretinal fluid accumulation was seen in 92 per cent (23 eyes) and 82.3 per cent (14 eyes) of the acute and chronic central serous chorioretinopathy groups, respectively. In two eyes (11.6 per cent) with chronic CSR, hyperautofluorescent changes were noted at the previous leakage points. In the acute CSR group, speckled hyperautofluorescence was detected in nine eyes (36 per cent) after the resolution of subretinal fluid. In the chronic CSR group, simultaneous speckled hyperautofluorescence was detected in the previous areas of subretinal fluid accumulation in 12 eyes (70.5 per cent).Conclusion: Fundus autofluorescence imaging delineates endogenous fluorescence derived mainly from lipofuscin within the retinal pigment epithelium (RPE) layer and therefore permits evaluation of functional alterations in the RPE in numerous retinal diseases. Data from fundus autofluorescence revealed distinctive findings in acute and chronic CSR. Fundus autofluorescence imaging may be used as a supplementary diagnostic tool for identifying patients with CSR and differentiation may be made between acute and chronic cases.

Vitamin D and cognition: A meta-analysis

Lipofuscin contained in the retinal pigment epithelium (RPE) is the main source of fundus autofluorescence (FAF), the target of an imaging method useful for estimating the progression of geographic atrophy (GA) in clinical trials. To establish a cellular basis for hyperfluorescent GA border zones, histologic autofluorescence (HAF) was measured at defined stages of RPE pathologic progression.Experimental study.Ten GA donor eyes (mean age ± standard deviation, 87.1±4.0 years) and 3 age-matched control eyes (mean age ± standard deviation, 84.0±7.2 years) without GA.The 10–micrometer-thick sections were divided into zones of RPE morphologic features according to an 8-point scale. Any HAF excited by 488 nm light was imaged by laser confocal microscopy. The HAF intensity summed along vertical lines perpendicular to Bruch's membrane at 0.2-μm intervals served as a surrogate for FAF. Intensity profiles in 151 zones were normalized to grade 0 at a standard reference location in each eye. Cross-sectional area, mean, and sum autofluorescence for individual RPE cells were measured (cellular autofluorescence [CAF]).Statistically significant differences in intensity and localization of HAF and CAF at defined stages of RPE morphologic progression for GA and control eyes.The RPE morphologic features were most abnormal (cell rounding, sloughing, and layering; grade 2) and HAF intensity profiles were highest and most variable immediately adjacent to atrophic areas. Peaks in HAF intensity frequently were associated with vertically superimposed cells. The HAF value that optimally separated reactive RPE was 0.66 standard deviations more than the mean for uninvolved RPE and was associated with a sensitivity of 75.8% and a specificity of 76.3%. When variable cell area was accounted for, neither mean nor sum CAF differed significantly among the RPE pathologic grades.Areas with advanced RPE alterations are most likely to exhibit clinically recognizable patterns of elevated FAF around GA, but may not predict cells about to die, because of vertically superimposed cells and cellular fragments. These data do not support a role for lipofuscin-related cell death and call into question the rationale of treatments targeting lipofuscin.The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Age-Related Macular Degeneration and Risk Factors for the Development of Choroidal Neovascularisation in the Fellow Eye: A 3-Year Follow-Up Study

Introduction: The presence of large-sized drusen (≧125 µm), soft indistinct drusen, pigmentary changes, a large area of drusen and a choroidal neovascular membrane in one eye have been found to be predictive risk factors of late exudative age-related macular degeneration (AMD). Multimodal imaging potentially increases the possibility of indentifying further potential risk factors of developing wet AMD. Purpose: To identify morphological and/or functional baseline risk factors for the development of choroidal neovascularization (CNV) in a multimodal set of images from fellow eyes of patients with exudative AMD. Methods: Single-center, prospective, observational, longitudinal 2-year plus 1-year extension study of 62 patients with neovascular AMD in one eye (the nonstudy eye) and early age-related maculopathy (ARM) in the fellow eye (study eye). Best-corrected ETDRS visual acuity, fluorescein angiography (FA) and indocyanine green angiography (ICG), fundus photography, retinal leakage analysis, fundus autofluorescence imaging and optical coherence tomography (OCT Stratus 4.0.2, Carl Zeiss Meditech Inc.) were performed at baseline and every 6 months in order to identify both conversion to CNV as well as possible predictive features present before conversion. A semiautomated computer-assisted grading system was used for classifying fundus color images. Only eyes with 3 years of follow-up were considered for statistical analysis. Results: Fifty-two patients completed the 3-year study follow-up: 26 men and 26 women aged from 56 to 92 years (mean ± SD: 76 ± 6 years). CNV confirmed with FA developed in 46% of the 52 study eyes during the 3-year follow-up (24 converted eyes: 7 in the first year, 11 in the second and 6 in the third). A significantly higher risk for conversion to wet AMD was found only for leakage on a retinal leakage analyzer (odds ratio, OR = 5.0; 95% confidence interval, CI = 1.5–16.4; p = 0.006) detected at least in one visit before the onset of exudative lesions, for baseline ICG hot spots (OR = 7.2; 95% CI = 2.0–25.7; p = 0.002), baseline late ICG hot spots (OR = 4.7; 95% CI = 1.4–15.4; p = 0.009) and baseline early ICG hypofluorescent spots (OR = 3.7; 95% CI = 1.2–12.1; p = 0.025). The total area of drusen, the area of drusen in subfield 1, inner circle or outer circle, the total number of drusen and the number of drusen ≧125 µm, fundus autofluorescence patterns, OCT findings and the severity of ARM at baseline did not show any correlation with an increased risk of conversion to wet AMD. Conclusion: At 3 years, progression from early to late exudative AMD was superior to the expected rate (44%). ICG early and late hyperfluorescent spots or areas, ICG early hypofluorescent spots or areas and early leakage detected with the retinal leakage analyzer, but not pigmentary changes, large drusen, number and area of drusen at any location or a greater severity of ARM at baseline, showed to be a predictive parameter of conversion to wet AMD.