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.
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.
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.
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.
MEWDS; Spectralis OCT; NIR-FAF; BL-FAF; mf-ERG
Background: With the advent of confocal scanning laser ophthalmoscopes (cSLO), fundus autofluorescence (FAF) resulting mainly from lipofuscin accumulation on the level of the retinal pigment epithelium can be visualised in vivo. Various cSLOs are available to document FAF. The authors analysed and compared results of FAF using three different instruments.
Methods: Eight eyes of eight normal volunteers and 18 eyes of 12 patients with different retinal diseases (age related macular degeneration, macular dystrophy, central serous retinopathy) were examined. FAF images were recorded from each subject with the Heidelberg retina angiograph (HRA), the Rodenstock cSLO (RcSLO) and the Zeiss Prototype SM 30-4024 (ZcSLO). For excitation an argon laser (488 nm) was used (barrier filter: HRA 500 nm; RcSLO 515 nm; ZcSLO 521 nm). 32 FAF images were aligned and averaged using the same software for all cSLOs. FAF distribution was measured and grey scale values as well as root mean square (RMS) contrast were compared.
Results: Mean age of all subjects was 55.5 (SD 21.4) years. The maximum grey scale value averaged across all eyes was 76.19 (39.34) for the HRA, 61.44 (22.12) for the ZcSLO and 37.0 (9.97) for the RcSLO. The RMS contrast was 0.46 (0.20) for the ZcSLO, 0.40 (0.12) for the HRA, and 0.13 (0.05) for the RcSLO. The differences between the cSLOs were statistically significant with higher grey scale levels and more contrast for the HRA and ZcSLO than the RcSLO (repeated measures ANOVA; p<0.0001). The differences between the HRA and the ZcSLO were not significant (post hoc comparisons; p<0.05).
Conclusions: All cSLOs allow clinically useful FAF imaging in retinal diseases. However, grey scale levels and contrast were much lower on the RcSLO. Therefore, RcSLO images appear much darker than HRA or ZcSLO images. Furthermore, not all cSLOs have a fixed photodetector gain and a standardised value for the argon laser amplification, which is mandatory for an absolute comparison of FAF imaging results.
scanning laser ophthalmoscope; fundus autofluorescence; lipofuscin; retinal pigment epithelium; macular degeneration
To assess the prevalence of peripheral fundus autofluorescence (FAF) abnormalities in a variety of diseases seen at a tertiary retina clinic.
We conducted a retrospective review of cases seen at the Doheny Eye Institute between November 2009 and May 2011, who had ultra-widefield FAF and pseudocolor imaging performed on new models of scanning laser ophthalmoscopes. Patients with a history of previous therapies that could alter the FAF findings, including vitrectomy, cryotherapy, laser photocoagulation, or photodynamic therapy, were excluded from the analysis. Based on their primary diagnosis the eyes were grouped into nine disease categories: age-related macular degeneration, central serous retinopathy, dystrophy, inflammatory disorders, ocular tumor, retinal vascular disorders, other, normal, and unknown. All FAF and accompanying pseudocolor images were reviewed independently by two reading center–certified graders.
A total of 470 eyes of 248 patients were included for analysis of which 461 eyes had images of sufficient quality for grading. The prevalence of peripheral findings was 65.5% (n = 302) for FAF images and 68.5% (n = 316) for the pseudocolor images (P < 0.001). The prevalence of peripheral abnormalities differed significantly between the disease categories ranging from 18.5% to 82.2% for FAF and 18.5% to 82.4% for pseudocolor images.
Peripheral FAF abnormalities are frequent and readily revealed by FAF imaging. Interestingly, even cases with presumably macular disease demonstrated a high prevalence of peripheral findings. Further investigation in prospective studies is warranted.
Peripheral abnormalities on ultra-widefield autofluorescence images are common in a large variety of diseases and reliably identifiable. There is a high correspondence between changes seen on autofluorescence and pseudocolor images. Peripheral changes in ultra-widefield imaging are a common finding in a variety of different diseases.
Background and objectives
Detection of peripheral fundus autofluorescence (FAF) using conventional scanning laser ophthalmoscopes (SLOs) is difficult and requires pupil dilation. Here we evaluated the diagnostic properties of wide-field FAF detected by a two-laser wavelength wide-field SLO in uveitis patients.
Study design/materials and methods
Observational case series of four patients suffering from different types of posterior uveitis/chorioretinitis. Wide-field FAF images were compared to visual fields. Panretinal FAF was detected by a newly developed SLO, which allows FAF imaging of up to 200° of the retina in one scan without the need for pupil dilation. Visual fields were obtained by Goldmann manual perimetry.
Findings from wide-field FAF imaging showed correspondence to visual field defects in all cases.
Wide-field FAF allowed the detection of visual field defect-related alterations of the retinal pigment epithelium in all four uveitis cases.
fundus autofluorescence (FAF); Optomap; wide-field scanning laser ophthalmoscopy; imaging; uveitis; visual field
To describe the retinal imaging findings in the index patient with Heimler syndrome (OMIM #234580).
Non-interventional case report.
A 29-year-old woman with Heimler syndrome developed bilateral vision loss. Fluorescein angiography (FA), fundus autofluorescence (FAF), spectral domain optical coherence tomography (SD-OCT) and electroretinography (ERG) were performed to assess the retinal anatomy and function.
FA showed mottling of the retinal pigment epithelium (RPE) in the posterior pole and periphery of the retina. FAF revealed hyper and hypoautofluorescent dots corresponding to the RPE mottling observed on FA. SD-OCT documented loss of the inner/outer segments boundary, and RPE thinning. ERG testing excluded generalized rod-cone dysfunction.
We report an adult-onset macular dystrophy in one of the previously reported patients with Heimler syndrome and hypothesize that this syndrome is probably an expression of a ciliopathy.
Amelogenesis imperfecta; Ciliopathy; Deafness; Heimler syndrome; Nail abnormalities; Retina
Best vitelliform macular dystrophy (BVMD) is a rare autosomal dominant retinal disease of highly variable phenotypic expression. Interpretations of disease mechanisms based on histopathology, electrophysiology, genetic analysis, and retinal imaging are somewhat discordant in fundamental issues such as the location and extension of primary retinal changes. Herein we describe the morphological macular features in patients with BVMD undergoing simultaneous multimodal fundus imaging and compare to those of normal age-matched subjects.
Comparative study including seven patients with BVMD (14 eyes) and seven age-matched healthy subjects (14 eyes). All participants were submitted to complete ophthalmological examination, fundus photography, and standardized multimodal fundus imaging protocol including Fourier-domain optical coherence tomography (Fd-OCT) combined with near-infrared reflectance and blue-light fundus autofluorescence (FAF).
In two eyes in the “subclinical” stage, Fd-OCT revealed thickening of the middle highly reflective layer (HRL) localized between the photoreceptors’ inner/outer segments junction (inner-HRL) and RPE/Bruch’s membrane reflective complex (outer-HRL) throughout the macula. In one eye in the “vitelliform” stage, a homogeneous hyper-reflective material on Fd-OCT was observed between the middle-HRL and outer-HRL; this material presented increased fluorescence on FAF. The outer nuclear layer (ONL) was thinned in the central macula and subretinal fluid was not identified in these earlier disease stages. In patients of “pseudohypopyon” (two eyes), “vitelliruptive” (eight eyes) and “atrophic” (one eye) stages, Fd-OCT revealed a variety of changes in the middle- and inner-HRLs and thinning of ONL. These changes were found to be associated with the level of visual acuity observed. Thickening of the middle-HRL was observed beyond the limits of the clinically evident macular lesion in all eyes.
Multimodal fundus imaging demonstrated thickening of the reflective layer corresponding to the photoreceptors’ outer segments throughout the macula with no subretinal fluid accumulation as the earliest detectable feature in BVMD. Changes detected in the photoreceptors’ reflective layers (middle- and inner- HRLs) and ONL thinning seemed to be progressive with direct implications for the level of visual acuity impairment observed among the different stages of the disease.
Best disease; Fourier-domain; Fundus autofluorescence; Infrared; Retinal pigment epithelium; Spectral; Tomography, optical coherence; Vitelliform macular dystrophy
To correlate the degree of functional loss with structural changes in patients with Stargardt disease.
Eighteen eyes of 10 Stargardt patients were studied. Scanning laser ophthalmoscope (SLO) infrared images were compared to corresponding spectral domain optical coherence tomography (SD-OCT) scans. Additionally, SLO microperimetry was performed and results were superimposed on SLO infrared images and in selected cases on fundus autofluorescence (FAF) images.
Seventeen of 18 eyes showed a distinct hypo-reflective foveal and/or perifoveal area with distinct borders on SLO-infrared images which was less evident on funduscopy and incompletely depicted in FAF images. This hypo-reflective zone corresponded to areas of significantly elevated psychophysical thresholds on microperimetry testing, in addition to thinning of the retinal pigment epithelium (RPE), disorganization or loss of the photoreceptor cell inner-outer segment (IS-OS) junction and external limiting membrane (ELM) on SD-OCT.
SLO-infrared fundus images are useful for depicting retinal structural changes in Stargardt patients. An SD-OCT/SLO microperimetry device allows for a direct correlation of structural abnormalities with functional defects that will likely be applicable for the determination of retinal areas for potential improvement of retinal function in these patients during future clinical trials and for the monitoring of the diseases' natural history.
microperimetry; SLO infrared imaging; Stargardt disease; fundus autofluorescence imaging
Objective. To describe the diverse patterns observed with the use of autofluorescence fundus photography (FAF) in patients with Birdshot chorioretinopathy (BSCR). Methods. A chart review of patients with BSCR seen at the Massachusetts Eye Research and Surgery Institution, who had autofluorescence fundus photography. The data obtained included age, gender, presence of the HLA-A29 haplotype, and current treatment. Results. Eighteen eyes with HLA-A29 associated BSCR were included. Four eyes presented with active inflammation. Correspondence of the lesions noted in the colour fundus photograph was observed in 3 eyes which were more easily identified with the FAF. Fifteen eyes had fundus lesions more numerous and evident in the FAF than in the colour fundus photograph.
Conclusion. Because FAF testing provides valuable insight into the metabolic state of the PR/RPE-complex, it may serve as a useful noninvasive assessment tool in patients with posterior uveitis in which the outer retina-RPE-choriocapillaries-complex is involved.
To establish a grading system of eye bank eyes using fundus autofluorescence (FAF) and identify a methodology that correlates FAF to age-related macular degeneration (AMD) with clinical correlation to the Age-Related Eye Disease Study (AREDS).
Two hundred sixty-two eye bank eyes were evaluated using a standardized analysis of FAF. Measurements were taken with the confocal scanning laser ophthalmoscope (cSLO). First, high-resolution, digital, stereoscopic, color images were obtained and graded according to AREDS criteria. With the neurosensory retina removed, mean FAF values were obtained from cSLO images using software analysis that excludes areas of atrophy and other artifact, generating an FAF value from a grading template. Age and AMD grade were compared to FAF values. An internal fluorescence reference standard was tested.
Standardization of the cSLO machine demonstrated that reliable data could be acquired after a 1-hour warm-up. Images obtained prior to 1 hour had falsely elevated levels of FAF. In this initial analysis, there was no statistical correlation of age to mean FAF. There was a statistically significant decrease in FAF from AREDS grade 1, 2 to 3, 4 (P < .0001). An internal fluorescent standard may serve as a quantitative reference.
The Minnesota Grading System (MGS) of FAF (MGS-FAF) establishes a standardized methodology for grading eye bank tissue to quantify FAF compounds in the retinal pigment epithelium and correlate these findings to the AREDS. Future studies could then correlate specific FAF to the aging process, histopathology AMD phenotypes, and other maculopathies, as well as to analyze the biochemistry of autofluorescent fluorophores.
Background. To describe the standard autofluorescence (FAF), the near infrared autofluorescence (NIA) and optical coherence tomography (OCT) patterns in central serous chorioretinopathy, correlating them with fluorescein angiography. Methods. Cross-sectional observational study, in which patients with at least seven months of CSC underwent ophthalmologic examination, fundus photography, FAF, NIA, fluorescein angiography (FA), and spectral-domain OCT. Results. Seventeen eyes of thirteen patients were included. The presentation features were a mottled hyperFAF in the detached area and areas with pigment mottling. NIA images showed areas of hyperNIA similar to FAF and localized areas of hypoNIA, which correlated with the points of leakage in the FA. OCT showed pigment epithelium detachment at the location of these hypoNIA spots. Discussion. FAF showed increased presence of fluorophores in the area of retinal detachment, which is believed to appear secondary to lipofuscin accumulation in the RPE or the presence of debris in the subretinal fluid. NIA has been related to the choroidal melanin content and there were areas of both increased and decreased NIA, which could be explained by damage ahead the retina, basically RPE and choroid. These findings, along with the PEDs found in the areas of hypoNIA, support the notion of a primary choroidal disease in CSC.
We report a case of neurofibromatosis type 1 (NF1) examined by infrared fundus autofluorescence (IR-FAF) and optical coherence tomography (OCT) to characterize the associated choroidal abnormalities. The conventional ophthalmoscopic findings were unremarkable. However, IR-FAF revealed multiple bright patchy lesions in the choroid of the posterior pole, in both eyes. OCT demonstrated irregular hyperreflectivity at the sites of these lesions. Patients with NF1 may have typical choroidal lesions that are visible on IR-FAF, which can be confirmed through OCT.
Aim: To describe and classify patterns of abnormal fundus autofluorescence (FAF) in the junctional zone of geographic atrophy (GA) in patients with age related macular degeneration.
Methods: Digital FAF images were recorded in 164 eyes of 107 patients using a confocal scanning laser ophthalmoscope (cSLO; excitation 488 nm, detection above 500 nm) as part of a prospective multicentre natural history study (FAM Study). FAF images were obtained in accordance with a standardised protocol for digital image acquisition and generation of mean images after automated alignment.
Results: Image quality was sufficient for classification of FAF patterns in 149 eyes (90.9%) with lens opacities being the most common reason for insufficient image quality. Abnormal FAF outside GA in 149 eyes was classified into four patterns: focal (12.1%), banded (12.8%), patchy (2.0%), and diffuse (57.0%), whereby 12.1% had normal background FAF in the junctional zone. In 4% there was no predominant pattern. The diffuse pattern was subdivided into four groups including reticular (4.7%), branching (27.5%), fine granular (18.1%), and fine granular with peripheral punctate spots (6.7%).
Conclusions: Different phenotypic patterns of abnormal FAF in the junctional zone of GA can be identified with cSLO FAF imaging. These distinct patterns may reflect heterogeneity at a cellular and molecular level in contrast with a non-specific ageing process. A refined phenotypic classification may be helpful to identify prognostic determinants for the spread of atrophy and visual loss, for identification of genetic risk factors as well as for the design of future interventional trials.
fundus autofluorescence; confocal scanning laser ophthalmoscopy; age related macular disease; geographic atrophy; retinal imaging
To report two cases of atypical vitelliform macular dystrophy misdiagnosed as chronic central serous chorioretinopathy.
Two patients with incidentally discovered abnormalities of the retina without specific symptoms were referred to our hospital for consultation. Bilateral macula atrophic lesions were observed and optical coherence tomography revealed serous retinal detachment in the macula. Fluorescein angiography showed multiple leakages around the central hypofluorescent area and indocyanine green angiography showed partially dilated choroidal vessels. Fundus autofluorescence (FAF) showed a decreasing pattern of autofluorescence in the subretinal fluid area, and increasing autofluorescence at the border of the serous retinal detachment. Both patients were diagnosed with chronic central serous chorioretinopathy. Photodynamic therapy and intravitreal bevacizumab injection were administered for engorged choroidal vessels during follow-up, but neither patient showed improvement in symptoms or ophthalmologic findings. Based on re-evaluation by fundus photography, optical coherence tomography, fluorescein angiography, and comparison of the results of FAF with the first visit, vitelliform macular dystrophy was suspected and a definite diagnosis was made by electrooculography and genetic testing.
In patients with continuous serous retinal detachment without response to photodynamic therapy or intravitreal bevacizumab injection, careful fundus exam and FAF can be used to diagnose atypical vitelliform macular dystrophy.
AIM—To describe a new method of evaluating the topographic distribution of fundus autofluorescence in eyes with retinal disease.
METHODS—Images of fundus autofluorescence were obtained in five patients and 34 normal volunteers using a confocal scanning laser ophthalmoscope (cSLO). To evaluate the topographic distribution of fundus autofluorescence throughout the posterior pole a rectangular box, 10 × 750 pixels, was used as the area of analysis. The box was placed, horizontally, across the macular region. The intensity of fundus autofluorescence of each pixel within the rectangular box was plotted against its degree of eccentricity. Profiles of fundus autofluorescence from patients were compared with those obtained from the age matched control group and with cSLO images.
RESULTS—Profiles of fundus autofluorescence appeared to represent the topographic distribution of fundus autofluorescence throughout the posterior pole appreciated in the cSLO images, and allowed rapid identification and quantification of areas of increased or decreased fundus autofluorescence.
CONCLUSIONS—Fundus autofluorescence profiles appear to be useful to study the spatial distribution of fundus autofluorescence in eyes with retinal disease.
To report a series of three cases of neurofibromatosis type 1 examined by
near-infrared fundus autofluorescence (NIR-AF) with a scanning laser
ophthalmoscope and spectral-domain optical coherence tomography (OCT) to
show the characteristics of choroidal abnormalities.
Retrospective case series. Six eyes of three patients were examined by
conventional fundus examinations, near-infrared monochromatic light
reflectance (NIR-R) and NIR-AF, OCT, fluorescein angiography, and
indocyanine green angiography.
All eyes showed multiple bright patchy regions in the choroid of the
posterior pole with NIR-R. NIR-AF revealed high fluorescent regions of
similar sizes at fundus locations identical to those shown by NIR-R. In one
case, hypofluorescent regions were shown by indocyanine green angiography in
the bright fluorescent region shown by NIR-AF. The other two cases showed no
abnormality under conventional fundus examination or fluorescein
angiography. OCT images crossing the bright patchy region showed irregular
hyper-reflectivity in the choroid in two cases and hyporeflectivity in one
NIR-AF demonstrated that dense melanin was included in the choroidal nodules
of neurofibromatosis type 1. The choroidal nodules showed hyper- or
hyporeflectivity in the choroid on OCT, which did not affect the retinal
near-infrared fundus autofluorescence; neurofibromatosis type 1; choroidal nodule; melanin
Changing lipofuscin and melanin content in RPE cells has been hypothesized to contribute to Stargardt disease pathogenesis. Longitudinal study of autofluorescence in Stargardt disease which reflect changing fluorophore compositions can reveal aspects of disease progression not previously evident.
We examined the temporal-spatial patterns of fundus autofluorescence with excitation at both 488 nm (standard fundus autofluorescence, FAF) and 795nm (near infrared autofluorescence, NIA) in a longitudinal case series involving 8 eyes of 4 patients (range of follow-up = 11 to 57 months; mean = 39 months). Image processing was performed to analyze spatial and temporal cross-modality associations.
Longitudinal FAF imaging of fleck lesions revealed hyperautofluorescent lesions that extended in a centrifugal direction from the fovea with time. Patterns of spread were non-random and followed a radial path that leaves behind a trail of diminishing autofluorescence. Longitudinal NIA imaging also demonstrated centrifugal lesion spread, but with fewer hyperautofluorescent lesions, suggestive of more transient hyperautofluorescence and more rapid decay at longer wavelengths. FAF and NIA abnormalities were spatially correlated to each other, and together 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 RPE 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.
To describe and correlate the features of astrocytic hamartomas using multimodal imaging.
Prospective, non-comparative, observational case series.
This was a single-center study of 4 patients (8 eyes) with tuberous sclerosis complex. A complete ophthalmologic examination, fundus photography, fundus autofluorescence (FAF), infrared imaging, and spectral domain optical coherence tomography (SD-OCT) were performed for each patient. Images from each modality were analyzed and compared.
In 2 patients, infrared imaging and SD-OCT detected occult retinal astrocytic hamartomas that were not observed on clinical examination or color fundus photography. FAF demonstrated the greatest contrast between lesions and surrounding retina but failed to identity one occult lesion that was detected with infrared imaging and SD-OCT. SD-OCT revealed lesions arising from the retinal nerve fiber layer with overlying vitreous adhesions, hyperreflective dots, and optically empty spaces at all depths of the tumor. Hamartomas were hyporeflective on infrared imaging and hypoautofluorescent on FAF. FAF of some lesions demonstrated hyperautofluorescent spots.
Infrared imaging and SD-OCT aid in the detection of astrocytic hamartomas that are not visible on clinical examination or color fundus photography. SD-OCT enhances visualization of structural details. FAF is a useful adjunctive test to obtain greater contrast between lesions and surrounding retina. The ability to monitor structural changes over time in astrocytic hamartomas using SD-OCT may be beneficial for monitoring the success of systemic chemotherapy in the treatment of various tuberous sclerosis tumors.
astrocytic hamartoma; retina; scanning laser ophthalmoscope; autofluorescence; optical coherence tomography; tuberous sclerosis
To evaluate the validity of the novel and noninvasive retro-mode imaging modality of confocal scanning laser ophthalmoscopy (cSLO) for detecting the morphological features of polypoidal choroidal vasculopathy (PCV).
Prospective, observational, consecutive case series.
Twenty-six patients (29 eyes) with PCV were enrolled in this study. All patients underwent comprehensive ophthalmologic examinations and imaging studies, including retro-mode imaging, fundus autofluorescence (FAF), fundus photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and spectral-domain optical coherence tomography (SD-OCT). We investigated the retro-mode images and compared the results with those of SD-OCT, FFA and ICGA.
In the 29 PCV eyes, the retro-mode images clearly revealed polypoidal lesions in 27 (93.1%) eyes as well as branching vascular networks in 16 (55.2%) eyes. Others findings, including pigment epithelial detachment (PED) in 20 (69.0%) eyes, neuroretinal detachment (NRD) in 3 (10.3%) eyes, cystoid macular edema (CME) in 3 (10.3%) eyes, drusen in 4 (13.8%) eyes and minute granular changes of the retinal pigment epithelium (RPE) in 12 (41.3%) eyes, were also clearly visualized. When we compared the results with those of SD-OCT, FFA and ICGA, there was no significant difference between ICGA and retro-mode imaging for finding polypoidal lesions and (or) branching choroidal vascular networks (P>0.05). However, the rate of PED detection was significantly better with retro-mode imaging than with the ICGA (P<0.05). The differences were not statistically significant between SD-OCT and retro-mode imaging for detecting PED, NRD, CME, drusen and minute granular RPE changes (P>0.05). The differences were not statistically significant between FFA and retro-mode imaging for detecting PED, NRD, CME (P>0.05).
The novel and noninvasive retro-mode imaging by cSLO is able to clearly visualize the morphological features of PCV.
Purpose. To describe the findings of fundus autofluorescence (FAF) and optical coherence tomography (OCT) in patients with branch retinal vein occlusion (BRVO). Methods. In this institutional, retrospective, observational case series, FAF was evaluated in 65 eyes with BRVO in 64 consecutive patients and compared with visual acuity, OCT findings, and other clinical observations. Results. Five types of autofluorescence appeared during the course of BRVO: (1) petaloid-shaped hyperautofluorescence in the area of macular edema and (2) hyperautofluorescence coincident with yellow subretinal deposits. (3) Diffuse hyperautofluorescence appeared within the area of serous retinal detachment (SRD) and OCT showed precipitates on the undersurface of the retina in 5/5 of these eyes (100%). (4) The area of vein occlusion showed diffuse hyperautofluorescence after resolution of the retinal bleeding. (5) Hard exudates exhibited hyper- or hypoautofluorescence. OCT indicated that most of the hard exudates with hyperautofluorescence were located on the retinal pigment epithelium. Conclusions. Hyperautofluorescence associated with subretinal fluid or hard exudate appeared in the subretinal space. This type of hyperautofluorescence may be attributed to blood cell or macrophages. FAF and OCT are noninvasive modalities that provide additional information regarding macular edema due to BRVO.
To identify the prevalence of rhodopsin (RHO) mutations in French patients with autosomal dominant rod-cone dystrophies (adRP).
Detailed phenotypic characterization was performed including precise family history, best corrected visual acuity using the ETDRS chart, slit lamp examination, kinetic and static perimetry, full field and multifocal electroretinography (ERG), fundus autofluorescence imaging (FAF) and optical coherence tomography (OCT). For genetic diagnosis, genomic DNA of seventy-nine families was isolated by standard methods. The coding exons and flanking intronic regions of RHO were PCR amplified, purified and sequenced in the index patient.
Among this French adRP cohort, 16.5% revealed a RHO mutation. While three unrelated families showed each a novel missense mutation (p.Leu88Pro, p.Met207Lys and p.Gln344Pro), ten unrelated families showed recurrent previously published mutations (p.Asn15Ser, p.Leu131Pro, p.Arg135Trp, p.Ser334GlyfsX20 and p.Pro347Leu). All mutations co-segregated with the phenotype within a family and the novel mutations were not identified in a control population.
Our studies revealed that the prevalence of RHO mutations in French adRP patients is in accordance with other studies from Europe. Most of the changes identified herein reflect recurrent mutations within which p.Pro347Leu substitution is the most prevalent. Nevertheless, almost a quarter of the changes are novel indicating that, although RHO is the first gene implicated and probably the most studied gene in RP, it is still relevant to perform mutation analysis in the coding exons of RHO to detect novel changes. Our detailed phenotype-genotype analyses in all family members available deliver the basis for therapeutic approaches in those families.
Adolescent; Adult; Child; DNA Mutational Analysis; Electroretinography; European Continental Ancestry Group; genetics; Female; Fluorescein Angiography; France; epidemiology; Genes, Dominant; Genotype; Humans; Male; Middle Aged; Mutation; Pedigree; Phenotype; Photoreceptor Cells, Vertebrate; pathology; Polymerase Chain Reaction; Prevalence; Retinitis Pigmentosa; diagnosis; genetics; Rhodopsin; genetics; Tomography, Optical Coherence; Visual Acuity; Young Adult
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, and to describe the effect of treatment on FAF.
Retrospective chart review of 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 a complete correlation, partial correlation, or no correlation. The posttreatment FAF photographs of 6 patients with choroidal melanoma who were managed with plaque radiotherapy or plaque radiotherapy and transpupillary thermotherapy were also analyzed.
Lipofuscin was present in 13 tumors, hyperpigmentation in 9 tumors, drusen in 6 tumors, and fibrous metaplasia in 4 tumors. A complete correlation between increased FAF and lipofuscin was found in 8 tumors (61.5%), a partial correlation in 3 tumors (23.1%), and no correlation in 2 tumors (15.4%). A complete correlation between hyperpigmentation and increased FAF was found in 5 tumors (55.6%), a partial correlation in 3 tumors (33.3%), and no correlation in 1 tumor (11.1%). A partial correlation was found between drusen and increased FAF in all 4 tumors. A partial correlation was found between fibrous metaplasia and increased FAF in all 3 tumors. Following treatment, increased FAF was observed in 6 choroidal melanomas owing to an increase in lipofuscin and hyperpigmentation.
Choroidal melanocytic lesions with overlying lipofuscin and hyperpigmentation are associated with increased FAF in about 90% of cases. Fundus autofluorescence photography may be helpful in evaluating small melanocytic tumors, since lipofuscin is a risk factor for growth. Following treatment, choroidal melanomas may show increased FAF.
To describe fundus autofluorescence (FAF) finding in a case of cone dystrophy.
Interventional case report.
A 23-year-old woman presented with increasing photophobia and decreasing vision in both eyes for 2 years. Fundus examination showed several drusen-like dots. FAF revealed hyper-autofluorescence in the foveola. Electroretinogram (ERG) demonstrated a pure “cone” dystrophy.
Hyper-autofluorescence in the foveola is a non-specific manifestation of photoreceptor-retinal pigment epithelium dysfunction. ERG studies are essential for accurate diagnosis.
Cone dystrophy; Electroretinogram; Fundus autofluorescence; Optical coherent tomography
To establish the characteristics of secondary retinal and retinal pigment epithelial (RPE) changes associated with the presence of choroidal melanoma and choroidal nevus as documented by optical coherence tomography (OCT) and fundus autofluorescence (FAF).
Materials and Methods:
PubMed review of major English publications examining the correlation between clinical characteristics of choroidal melanoma and nevus with OCT and FAF findings.
The intrinsic properties of choroidal melanoma, as well as overlying RPE changes, drusen, and lipofuscin are best characterized by FAF, while OCT is more sensitive for the identification of subretinal and intraretinal fluid as well as atrophy, degeneration, and photoreceptor loss in the neurosensory retina.
Secondary retinal changes associated with choroidal melanocytic lesions can be documented by OCT and FAF. OCT-evident changes are observed more often with choroidal melanoma than choroidal nevus. OCT is better suited to identify the overlying retinal detachment and edema, even before these findings are clinically apparent. FAF is most useful in documenting the presence of lipofuscin, a finding that represents one of the important criteria in differentiating small choroidal melanoma from benign choroidal nevus.
Autofluorescence; Choroid; Eye; Melanoma; Nevus; Optical Coherence Tomography
Standardized imaging procedures allow quantitative and qualitative assessment of fundus autofluorescence in mice. The technique will be useful as an outcome measure in preclinical trials aimed at lowering RPE-lipofuscin and for correlating findings on fundus autofluorescence with postmortem analysis.
To investigate the feasibility and to identify sources of experimental variability of quantitative and qualitative fundus autofluorescence (AF) assessment in mice.
Blue (488 nm) and near-infrared (790 nm) fundus AF imaging was performed in various mouse strains and disease models (129S2, C57Bl/6, Abca4−/−, C3H-Pde6brd1/rd1, Rho−/−, and BALB/c mice) using a commercially available scanning laser ophthalmoscope. Gray-level analysis was used to explore factors influencing fundus AF measurements.
A contact lens avoided cataract development and resulted in consistent fundus AF recordings. Fundus illumination and magnification were sensitive to changes of the camera position. Standardized adjustment of the recorded confocal plane and consideration of the pupil area allowed reproducible recording of fundus AF from the retinal pigment epithelium with an intersession coefficient of repeatability of ±22%. Photopigment bleaching occurred during the first 1.5 seconds of exposure to 488 nm blue light (∼10 mW/cm2), resulting in an increase of fundus AF. In addition, there was a slight decrease in fundus AF during prolonged blue light exposure. Fundus AF at 488 nm was low in animals with an absence of a normal visual cycle, and high in BALB/c and Abca4−/− mice. Degenerative alterations in Pde6brd1/rd1 and Rho−/− were reminiscent of findings in human retinal disease.
Investigation of retinal phenotypes in mice is possible in vivo using standardized fundus AF imaging. Correlation with postmortem analysis is likely to lead to further understanding of human disease phenotypes and of retinal degenerations in general. Fundus AF imaging may be useful as an outcome measure in preclinical trials, such as for monitoring effects aimed at lowering lipofuscin accumulation in the retinal pigment epithelium.
To improve our understanding of Stargardt disease by comparing structural changes seen on spectral domain optical coherence tomography (SD-OCT) to those visible on fundus autofluorescence (FAF).
FAF and SD-OCT were obtained on 22 eyes of 11 patients with Stargardt disease. SD-OCT images were obtained at the fovea and at the eccentric preferred retinal locus (PRL). The diameters of “absent” (hypo-autofluorescent) and “abnormal” FAF areas were measured. The extent of the transverse defect of the junction between the inner and outer segments of the photoreceptors (IS-OS) was measured in the foveal area. The PRL was evaluated with fundus photography and microperimetry.
Twenty-one of 22 eyes showed defective FAF. For 17 eyes, FAF was absent in the fovea and for 4 eyes the FAF was abnormal. All eyes showed disorganization and/or loss of the IS-OS junction in the foveal area on SD-OCT. The diameter of the absent FAF area was smaller than the measurement of the IS-OS junction loss; the latter was closer to the diameter of the abnormal FAF area. Seventeen eyes had an eccentric PRL associated with a retinal area with no defects on FAF.
For the majority of eyes changes on SD-OCT correlated well with changes on FAF. However for 3 patients, photoreceptor abnormalities were seen in the fovea on SD-OCT without an equivalent abnormality on FAF. This suggests that for these patients, the structural integrity of the photoreceptors may be affected earlier than changes in the RPE at least as detected by FAF.