Fundus autofluorescence (FAF) imaging is a noninvasive retinal imaging methodology that allows mapping of lipofuscin distribution in the retinal pigment epithelium cell (RPE). Excessive accumulation ...of lipofuscin granules in the lysosomal compartment of RPE cells represents a common downstream pathogenetic pathway in various hereditary and complex retinal diseases, including age-related macular degeneration. The clinical applications of FAF coupled with its ease of use, and the noninvasive nature of characterizing retinal diseases, are increasingly valuable to the field of ophthalmology and in assessing the progression of retinitis pigmentosa (RP). Quantitative AF (qAF) enhances the understanding of retinal disease processes, serves as a diagnostic aid, and allows for the monitoring of the effects of therapeutic interventions. This chapter introduces basic principles of FAF and general protocols of FAF evaluating retinal disease progression in rodents.
To evaluate manual and semiautomated grading techniques for assessing decreased fundus autofluorescence (DAF) in patients with Stargardt disease phenotype.
Certified reading center graders performed ...manual and semiautomated (region finder-based) grading of confocal scanning laser ophthalmoscopy (cSLO) fundus autofluorescence (FAF) images for 41 eyes of 22 patients. Lesion types were defined based on the black level and sharpness of the border: definite decreased autofluorescence (DDAF), well, and poorly demarcated questionably decreased autofluorescence (WDQDAF, PDQDAF). Agreement in grading between the two methods and inter- and intra-grader agreement was assessed by kappa coefficients (κ) and intraclass correlation coefficients (ICC).
The mean ± standard deviation (SD) area was 3.07 ± 3.02 mm for DDAF (n = 31), 1.53 ± 1.52 mm for WDQDAF (n = 9), and 6.94 ± 10.06 mm for PDQDAF (n = 17). The mean ± SD absolute difference in area between manual and semiautomated grading was 0.26 ± 0.28 mm for DDAF, 0.20 ± 0.26 mm for WDQDAF, and 4.05 ± 8.32 mm for PDQDAF. The ICC (95% confidence interval) for method comparison was 0.992 (0.984-0.996) for DDAF, 0.976 (0.922-0.993) for WDQDAF, and 0.648 (0.306-0.842) for PDQDAF. Inter- and intra-grader agreement in manual and semiautomated quantitative grading was better for DDAF (0.981-0.996) and WDQDAF (0.995-0.999) than for PDQDAF (0.715-0.993).
Manual and semiautomated grading methods showed similar levels of reproducibility for assessing areas of decreased autofluorescence in patients with Stargardt disease phenotype. Excellent agreement and reproducibility were observed for well demarcated lesions.
Purpose
To investigate retinal changes in β-thalassemia major patients and identify their association with systemic risk factors.
Methods
In this prospective study, 120 β-thalassemia major patients ...received complete ophthalmic examinations (best-corrected visual acuity, contrast sensitivity, color vision, and indirect ophthalmoscopy) and retinal imaging using color fundus photography and fundus autofluorescence imaging. Patients were grouped according to the presence of thalassemia-related retinal changes. The association between systemic risk factors (age, type and duration of iron chelator use, history of splenectomy, hemoglobin level, and ferritin level) and thalassemia-related retinal changes was investigated using logistic regression analysis.
Results
Thalassemia-related retinal changes were identified in 36.7% of patients. Several distinct retinal changes were observed, including retinal refractile bodies in 10% of patients and retinal hemorrhage in 5.8% of patients. Fundus autofluorescence imaging showed abnormal patterns in 36.3% of patients with thalassemia-related retinal changes and 18.4% of patients without thalassemia-related retinal changes. Age (odds ratio OR = 1.10, 95% confidence interval CI 1.03–1.18) and ferritin level (OR 1.16, 95% CI 1.01–1.33) were associated with thalassemia-related retinal changes.
Conclusion
Novel retinal changes were observed in β-thalassemia major patients. This study identified older age and higher ferritin level as risk factors for thalassemia-related retinal changes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Pathogenic variants in DNA-damage regulated autophagy modulator 2 gene (DRAM2) cause a rare autosomal recessive retinal dystrophy and its disease course is not well understood. We present two ...Slovenian patients harboring a novel DRAM2 variant and a detailed review of all 23 other patients described to date. Whole exome and whole genome sequencing were performed in the two patients, and both underwent ophthalmological examination with a 2-year follow-up. PubMed was searched for papers with clinical descriptions of DRAM2 retinopathy. Patient 1 was homozygous for a novel variant, p.Met1?, and presented with the acute onset of photopsia and retina-wide retinopathy at the age of 35 years. The patient was first thought to have an autoimmune retinopathy and was treated with mycophenolate mofetil, which provided some symptomatic relief. Patient 2 was compound heterozygous for p.Met1? and p.Leu246Pro and presented with late-onset maculopathy at the age of 59 years. On review, patients with DRAM2 retinopathy usually present in the third decade with central visual loss, outer retinal layer loss on optical coherence tomography and a hyperautofluorescent ring on fundus autofluorescence. Either cone–rod or rod–cone dystrophy phenotype is observed on electroretinography, reflecting the importance of DRAM2 in both photoreceptor types. Non-null variants can result in milder disease.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Fundus autofluorescence (FAF) imaging is commonly used in ophthalmic clinics for
diagnosis and monitoring of retinal diseases. Lipofuscin in the retinal pigment
epithelium (RPE), with A2E as its most ...abundant component and a visual cycle
by-product, is the major fluorophore of FAF. Lipofuscin accumulates with age and
is implicated in degenerative retinal diseases. The amount of lipofuscin in RPE
can be assessed by quantitative measurement of FAF. However, the currently
available FAF imaging technologies are not capable of quantifying the absolute
intensity of FAF, which is essential for comparing images from different
individuals, and from the same individual over time. One major technical
difficulty is to compensate the signal attenuation by ocular media anterior to
the RPE (pre-RPE media). FAF intensity is also influenced by fluctuations in
imaging conditions such as illumination power and detector sensitivity, all of
which need to be compensated. In this review, we present the concept and
research progress of using visible-light optical coherence tomography-based
simultaneous multimodal retinal imaging to compensate signal attenuation by
pre-RPE media and the influence of parameters of the acquisition system for
accurate measurement of FAF intensities.
Impact statement
Quantitative fundus autofluorescence imaging with simultaneous visible-light
optical coherence tomography-based multimodal technology has potential
significant impact on the diagnosis and monitoring the progression of
retinal diseases.
To genetically characterize a subphenotype of geographic atrophy (GA) in AMD associated with rapid progression and a diffuse-trickling appearance on fundus autofluorescence imaging.
Patients from the ...Fundus Autofluorescence in Age-Related Macular Degeneration Study were phenotyped for diffuse-trickling GA (dt-GA; n = 44). DNA was analyzed for 10 known AMD-associated genetic variants. A genetic risk score (GRS) was calculated and compared with patients with nondiffuse-trickling GA (ndt-GA; n = 311) and individuals from the 1000 genomes project (1000G; n = 267). Given the phenotypic overlap between diffuse-trickling and late-onset retinal degeneration (LORD), all C1QTNF5 exons and their exon/intron boundaries were sequenced.
A statistically significant difference in allele frequencies between dt-GA and ndt-GA were found for CFH:rs1061170 and CFH:rs800292 (Pcorrected = 0.03). The ARMS2 variant rs10490924 was significantly more frequent in dt-GA than in 1000G individuals (Pcorrected < 0.01). The GRS of dt-GA patients was in-between the score of the 1000G individuals and that of patients with ndt-GA, significantly differing from both (Pcorrected <0.01). Sequencing of C1QTNF5 revealed 28 unique variants although none showed a statistically significant association with dt-GA when compared with 1000G individuals.
The dt-GA phenotype shows a remarkably different genetic risk profile from other GA phenotypes secondary to AMD. Disease-associated C1QTNF5 mutations were not identified. Together, these results suggest that the dt-GA phenotype is associated with a genetic background substantially different from other GA phenotypes and underlines the necessity to refine the clinical phenotyping, specifically when aiming for individualized therapies in AMD.
To investigate fundus autofluorescence (FAF) patterns in patients with nonexudative age-related macular degeneration (AMD) and to test if FAF patterns affect the development of choroidal ...neovascularization (CNV).
One hundred one patients with early AMD underwent a detailed ophthalmological examination. Fundus autofluorescence imaging was performed with a confocal scanning laser ophthalmoscope following a standard protocol. The classification of the International Fundus Autofluorescence Classification Group was used for the description of the FAF patterns.
One hundred seventy-eight eyes of 101 patients (59 women, 42 men) with a mean (±SD) age of 66.4 (±6.1) years were included. The mean (±SD) follow-up was 41.3 (±27) months. One hundred seventy-eight eyes presented various types of drusen with or without hyperpigmentation or hypopigmentation at initial examination. During follow-up, a total of 22 (12.3%) eyes developed CNV. The most frequent pattern for CNV development was the patchy pattern in 30.4%, followed by linear in 25%, and reticular pattern in 20.8% of eyes.
Fundus autofluorescence imaging using a confocal scanning laser ophthalmoscope is a useful technique to identify FAF characteristics in patients with nonexudative AMD. Different patterns of FAF abnormalities can be obtained in these eyes. Our results indicate that patchy, linear, and reticular patterns are the specific patterns associated with CNV development in nonexudative AMD.
To evaluate the role of bone marrow-derived stem cells in the treatment of advanced dry age-related macular degeneration (AMD) using multifocal electroretinogram (mf-ERG) and fundus autofluorescence ...imaging.
Thirty patients (60 eyes) with bilateral central geographic atrophy (GA) were recruited. Worse eye of each patient received autologous bone marrow-derived hematopoietic stem cells (BM-HSCs) (group 1) and the fellow eye with better visual acuity served as control (group 2). The effect of stem cell therapy was determined in terms of visual acuity, amplitude and implicit time in mf-ERG and size of GA on fundus autofluorescence imaging. These tests were performed at presentation and first, third and sixth month follow up. Adverse events (if any) were also monitored.
At 6mo follow-up there was no statistically significant improvement in median logMAR best corrected visual acuity (BCVA) in either group. Mf-ERG revealed significant improvement in amplitude and implicit time in the intervention group. A significant decrease was also noted in greatest linear dimension (GLD) of GA in the eyes receiving stem cells 6.78±2.60 mm at baseline to 6.56±2.59 mm at 6mo (
=0.021). However, no such improvement was noted in the control group.
Electrophysiological and anatomical improvement in the intervention group sheds light on the therapeutic role of BM-HSCs. Further studies are required to determine the stage of disease at which the maximal benefit can be achieved and to standardize the dose and frequency of stem cell injection.
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