Macular Autofluorescence Research Articles

Patterns of Fundus Autofluorescence in Eyes with Myopic Atrophy Maculopathy: A Consecutive Case Series Study

ABSTRACT Purposes: To investigate the patterns of fundus autofluorescence (FAF) in patients with different grades of myopic atrophy maculopathy (MAM). Methods: Patients with MAM who visited Zhongshan Ophthalmic Center from January 2018 to December 2019 were screened. All patients received comprehensive ophthalmologic examinations as well as FAF imaging. The atrophic severity of each eye was identified based on the META-PM classification system, including no myopic retinal lesions (C0), tessellated fundus only (C1), diffuse chorioretinal atrophy (C2), patchy chorioretinal atrophy (C3), and macular atrophy (C4). Results: Eighty-nine consecutive patients with 137 affected eyes were included. Four different autofluorescence (AF) patterns were detected: unremarkable AF (48 eyes in C1 and 18 eyes in C2, 48.2%), compound AF (2 eyes in C1 and 12 eyes in C2, 10.2%), patchy AF defect (5 eyes in C2 and 34 eyes in C3, 28.5%), and macular AF defect (18 eyes in C4, 13.1%). Moreover, AF patterns were significantly correlated with age (r = 0.419, P < .001), best-corrected visual acuity (BCVA) (r = 0.592, P < .001), axial length (AL) (r = 0.529, P < .001), and subfovial choroidal thickness (SFCT) (r = −0.728, P < .001). In addition, with the help of FAF, 14.3% (5/35) of eyes initially categorized as C2 merely based on color fundus photographs (CFP) should be categorized as C3. Conclusions: The severity of FAF in eyes with MAM was significantly correlated with myopic characteristics. FAF might be beneficial for detecting unremarkable patchy chorioretinal atrophy on CFP of MAM.

Detailed comparison of phenotype between male patients carrying variants in exons 1–14 and ORF15 of RPGR

PurposeTo compare disease severity in detail between patients carrying variants in exons 1–14 and ORF15 of retinitis pigmentosa GTPase regulator (RPGR). MethodsSystematic next-generation sequencing data analysis, Sanger sequencing validation and segregation analysis were utilised to identify the pathogenic variants. Detailed ophthalmic examinations, including electroretinograms, fundus photography, fundus autofluorescence and optical coherence tomography were performed. Statistical analysis, including age adjustment and comparison, were performed based on cross-sectional level to compare disease severity between variants in the two RPGR variant groups. ResultsSixty-two variants were identified in RPGR in 86 patients from 77 unrelated families. Twenty-nine (37.7%) had variants in RPGR-exons 1–14 (group 1) and 48 (62.3%) in RPGR-ORF15 (group 2). Eighty-four patients were diagnosed with X-linked retinitis pigmentosa and only two patients with cone-rod dystrophy. LogMAR visual acuity increased 0.035 and 0.022 each year on average in group 1 and group 2, respectively. Group 2 patients had better visual acuity with a mean logMAR difference of 0.4378, which is significant after age adjustment (P < 0.01). Neither the value of log (ellipsoid zone width) nor central retinal thickness was significantly correlated with variant grouping after considering the effect of the age variable (P = 0.56 and 0.40, respectively). Spherical refractive error did not differ significantly between the two variant groups (P = 0.17). Patterns of autofluorescence included a hyperfluorescent ring at the posterior pole, diffuse hyperfluorescence in the macular area, and dark macular autofluorescence with or without fovea hyperfluorescence. The age and proportion of fundus autofluorescence patterns between the two variant groups were significantly different (P < 0.01). ConclusionsPatients with variants in exons 1–14 retained less visual acuity than patients with ORF15 variants and deteriorated faster. However, the ellipsoid zone widths, central retinal thickness and refractions were comparable between the two groups. Autofluorescence pattern relates to the age and the variant grouping.

Photobleaching by Spectralis Fixation Target.

The aim of this study is to determine whether the cross-shaped fixation target in a spectral-domain optical coherence tomography instrument (Spectralis; Heidelberg Engineering) could produce a cross-shaped increase fundus autofluorescence artifact on subsequent imaging. Thirty eyes of 15 healthy volunteers (8 women and 7 men; mean [SD] age 24 [3] years) were included in the study, which was conducted between October 2015 and December 2015. In all eyes, a cross-shaped increase in macular autofluorescence with variable intensity occurred after Spectralis spectral-domain optical coherence tomography acquisition. This peculiar pattern was also detected on confocal scanning laser ophthalmoscope infrared reflectance and MultiColor imaging. Interestingly, no changes in macular fundus autofluorescence pattern were evident after optical coherence tomography acquisition with either Cirrus HD-OCT 5000 or RTVue XR Avanti. In an era characterized by extensive use of optical coherence tomography examination in clinical practice, the potential deleterious effects related to photopigments consumption by Spectralis optical coherence tomography fixation point deserve further investigation.

Impact of Macular Pigment on Fundus Autofluorescence Lifetimes.

To characterize the macular region and to investigate the influence of the macular pigment (MP) on fundus autofluorescence (FAF) lifetimes in vivo. Forty-eight healthy subjects with a mean age of 24.1 ± 3.6 years (range, 20-37 years) were included. A 30° retinal field was investigated using the fluorescence lifetime imaging ophthalmoscope (FLIO), based on a Heidelberg Engineering Spectralis system, detecting FAF decays in a short (498-560 nm; ch1)- and a long (560-720 nm; ch2)-wavelength channel. The mean fluorescence lifetime τm was calculated from a 3-exponential approximation of the FAF decays. Macular pigment optical density (MPOD) was measured by one-wavelength reflectometry, and macular optical coherence tomogram (OCT) scans were recorded. Correlations between τm and MPOD were analyzed. The τm showed shortest values at the macular region with a mean of 82 ps (ch1) and 126 ps (ch2). We found a strong correlation of τm to the MPOD (ch1: r = -0.760; ch2: r = -0.663; P < 0.001), as well as a topologic agreement of shortest τm with highest MPOD. Macular pigment, which is known to have very short fluorescence decays, considerably contributes to the macular autofluorescence (AF). This study gives indirect evidence for a strong impact of MP on macular τm, although no direct measurement of MP autofluorescence lifetimes in vivo is possible at this point. Potentially, imaging the FAF lifetimes could lead to a novel methodology for the detection of macular pigment properties and pathology-induced changes in the living human retina.

Macular auto-fluorescence is a follow-up parameter for cystoids macular edema.

This study aimed to evaluate if macular autofluorescence (MAF) is a valuable, non-invasive follow-up parameter for cystoid macular edema. A total of 71 eyes (71 cases) with cystoid macular edema (CME) were included in the study. Macular pigment (MP) was evaluated using HRA2 (infrared) IF and FA models. The density of MP was graded into three categories: without, partial, and normal amount of MP. A comparison was made between the baseline (before the first administration) level and at the fourth month, following three consecutive intravitreal lucentis injections every month. The morphology and distribution of MAF, and the density and distribution of MP were regarded as the main outcome measures. At the baseline visit, all eyes with CME had petaloid/irregular-shaped MAF in the macular area (100%). No MAF was detected in the control eyes (0). There was significant difference in MAF between the CME and normal groups (P=0.000). At the fourth monthly visit, normal levels of MP density without MAF was detected in 68 eyes (95.8%) with the best corrected spectacular visual acuity increasing to at least 1 line accordingly. We conclude that macular MAF can be used as a follow-up parameter for patients with CME. MP and MAF can indirectly reflect the fovea cone function.

Segmentation of Retinal Layers in Sjögren–Larsson Syndrome

Segmentation of Retinal Layers in Sjögren–Larsson Syndrome

Associations between autofluorescence abnormalities and visual acuity in idiopathic macular telangiectasia type 2: MacTel project report number 5.

The aim of this study was to determine whether typical abnormalities seen on autofluorescence (AF) imaging in patients with macular telangiectasia (MacTel) type 2 are correlated with visual acuity at presentation and with progression of visual loss over a 2-year follow-up period. A subgroup of 218 patients (413 eyes) enrolled in the MacTel study that underwent AF imaging was included in the present study. Images were graded at the Moorfields Eye Hospital Reading Center. Recorded AF abnormalities at baseline and at 2 years included the presence of increased AF because of loss of masking at the central macula, localized decreased AF at the end of a retinal vessel, and large area of decreased AF. Best-corrected visual acuity was measured using the Early Treatment for Diabetic Retinopathy chart at baseline and after 2 years. Statistical associations were sought by means of a generalized linear model. Presence of increased macular AF (P = 0.004), a large area of decreased AF (P < 0.001), or decreased AF at the end of a retinal vessel (P < 0.001) at baseline were significantly associated with worse best-corrected visual acuity. Presence of increased macular AF (P < 0.001) or of localized decreased AF at the end of a retinal vessel (P < 0.001) and the absence of a large area of decreased AF (P < 0.001) were predictive of a subtle but significant drop in best-corrected visual acuity at 2 years. Increased central AF at baseline heralds worse best-corrected visual acuity and predicts further subtle visual loss in a period of 2 years, which, however, does not stand out from the overall slowly progressive natural history of the disease.

Autofluorescence patterns and visual acuity in macular telangiectasia type 2

AbstractPurpose An analysis was performed with a view of determining potential associations between typical patterns seen on autofluorescence (AF) imaging in patients with Macular Telangiectesia (MacTel) type 2 and distance visual acuity at presentation as well as visual change over a 2‐year follow‐up period, thus ascribing predictive value to AF patterns in MacTel.Methods A subgroup of 135 patients (229 eyes) enrolled in the MacTel study underwent AF imaging. Images were graded at the Moorfields Eye Hospital Reading Centre. Recorded AF patterns at baseline and at two years included the typical pattern of increased central AF due to loss of foveal masking, localized decreased AF at the end of a retinal vessel and a large area of decreased AF. Best‐corrected visual acuity (BCVA) was measured by means of the Early Treatment for Diabetic Retinopathy Study charts at baseline and after two years. Statistical associations were derived by means of a generalized linear model.Results Presence of increased macular AF (p=0.004), a large area of decreased AF (p&lt;0.001) or decreased AF at the end of a retinal vessel (p&lt;0.001) at baseline were significantly associated with worse BCVA. Presence of increased macular AF (p&lt;0.001) or of localized decreased AF at the end of a retinal vessel (p&lt;0.001) and the absence of a large area of decreased AF (p&lt;0.001) were predictive of a subtle, but statistically significant drop in BCVA at 2 years.Conclusion The typical pattern of increased central AF at baseline is encountered in patients with worse BCVA in MacTel type 2 and is also predictive of further subtle visual loss in a period of two years. Decreased AF is found in patients with worse baseline BCVA though no further visual loss at two years is observed.

Spectral-domain optical coherence tomography and fundus autofluorescence findings in a case of laser pointer-induced maculopathy.

To describe the spectral-domain optical coherence tomography and fundus autofluorescence findings in a case of laser pointer-induced maculopathy. Observational case report of a patient with bilateral decreased visual acuity after exposure to a handheld green laser pointer. A 15-year-old boy presented with decreased vision after exposure to a green laser pointer. Fundoscopy revealed gray and yellowish round spots in the foveal area of both eyes. Fundus autofluorescence imaging revealed subtle changes of the normal background macular autofluorescence of the right eye, with hyperautofluorescence dots in the fovea of the left eye. Spectral-domain optical coherence tomography showed a variety of changes of the outer retina and retinal pigment epithelium, with disruption of the external limiting membrane, the photoreceptor ellipsoid zone of the inner segments, and the interdigitation zone in the foveal region in both eyes. Six months after laser exposure, fundoscopic examination showed persistent alterations at the level of the retinal pigment epithelium in the fovea in both eyes. Fundus autofluorescence revealed mild but persistent changes of the normal autofluorescent macular background in both eyes. Spectral-domain optical coherence tomography showed partial resolution of the outer retinal disruption noted on his initial visit with persistent, small foveal photoreceptor defects in both eyes. Laser pointer maculopathy may disturb the outer retinal architecture in a manner evident on spectral-domain optical coherence tomography and fundus autofluorescence, resulting in decreased visual acuity. Proper warnings should accompany these devices and access to them by minors should be limited.

Cone Structure in Retinal Degeneration Associated with Mutations in theperipherin/RDSGene

To study cone photoreceptor structure and function associated with mutations in the second intradiscal loop region of peripherin/RDS. High-resolution macular images were obtained with adaptive optics scanning laser ophthalmoscopy and spectral domain optical coherence tomography in four patients with peripherin/RDS mutations and 27 age-similar healthy subjects. Measures of retinal structure and fundus autofluorescence (AF) were correlated with visual function, including best-corrected visual acuity (BCVA), kinetic and static perimetry, fundus-guided microperimetry, full-field electroretinography (ERG), and multifocal ERG. The coding regions of the peripherin/RDS gene were sequenced in each patient. Heterozygous mutations in peripherin/RDS were predicted to affect protein structure in the second intradiscal domain in each patient (Arg172Trp, Gly208Asp, Pro210Arg and Cys213Tyr). BCVA was at least 20/32 in the study eye of each patient. Diffuse cone-greater-than-rod dysfunction was present in patient 1, while rod-greater-than-cone dysfunction was present in patient 4; macular outer retinal dysfunction was present in all patients. Macular AF was heterogeneous, and the photoreceptor-retinal pigment epithelial (RPE) junction layer showed increased reflectivity at the fovea in all patients except patient 1, who showed cone-rod dystrophy. Cone packing was irregular, and cone spacing was significantly increased (z-scores >2) at most locations throughout the central 4° in each patient. peripherin/RDS mutations produced diffuse AF abnormalities, disruption of the photoreceptor/RPE junction, and increased cone spacing, consistent with cone loss in the macula. The abnormalities observed suggest that the integrity of the second intradiscal domain of peripherin/RDS is critical for normal macular cone structure.

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

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. 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. 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. 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.

Fundus Autofluorescence and Central Serous Chorioretinopathy

To investigate the autofluorescence characteristics in patients with central serous chorioretinopathy. Observational case series. Thirty consecutive patients examined in a private referral practice. Patients were imaged with autofluorescence photography, fundus photography, fluorescein angiography, and optical coherence tomography (OCT). The mean and standard deviation (SD) of the grayscale values from a 100-pixel-diameter circle centered on the fovea were obtained and normalized with the level of autofluorescence of the posterior pole. There were 30 patients, 23 male (76.7%) and 7 female (23.3%), with a median visual acuity (VA) of 20/25 and a range of 20/15 to 20/400. Stepwise linear regression that included individual fixed effects found that normalized central macular autofluorescence (P < 0.001), pigment mottling in the fovea (P = 0.045), subfoveal fluid detected by OCT (P = 0.033), and the SD of the central macular autofluorescence (P = 0.025) produced a highly significant model (R2 = 0.92, P < < 0.001) predicting VA. Increasing levels of autofluorescence were correlated with accumulation of material on the outer surface of the retina as seen by OCT. Decreased central macular autofluorescence, particularly in those eyes with central geographic retinal pigment epithelial atrophy, was associated with poor VA. This study established that autofluorescence changes occurring in central serous chorioretinopathy with explicit patterns can be measured in a noninvasive manner, and this information can be used to estimate the damage induced by central serous chorioretinopathy with a high degree of statistical significance. We hypothesize that the material on the outer surface of the elevated retina may represent accumulation of photoreceptor outer segments secondary to the lack of direct apposition and phagocytosis by the retinal pigment epithelium.