Short-wave Fundus Autofluorescence Research Articles

Evolving Patterns of Hyperfluorescent Fundus Autofluorescence Accompany Retinal Atrophy in the Rat and Mimic Atrophic Age-Related Macular Degeneration

PurposeComplex two-dimensional (2D) patterns of hyperfluorescent short-wave fundus autofluorescence (FAF) at the border of geographic atrophy (GA) can predict its expansion in patients with late non-exudative “dry” AMD. However, preclinical models do not phenocopy this important feature of disease. We sought to describe the spatiotemporal changes in hyperfluorescent FAF patterns that occur following acute oxidative stress, potentially in association with GA expansion.MethodsSprague Dawley rats (n = 54) received systemic sodium iodate (25–45 mg/kg, n = 90 eyes) or saline (n = 18 eyes) and underwent serial full fundus imaging by confocal scanning laser ophthalmoscopy, including blue FAF and delayed near-infrared analysis. Composite images of the fundus were assembled, and the 2D patterns were described qualitatively and quantitatively. A subset of eyes underwent tissue analysis, and four underwent optical coherence tomography (OCT) imaging.ResultsReproducibly changing, complex patterns of hyperfluorescent FAF emerge at the borders of toxin-induced damage; however, in the absence of GA expansion, they percolate inward within the region of retinal pigment epithelium loss, evolving, maturing, and senescing in situ over time. Unexpectedly, the late FAF patterns most closely resemble the diffuse tricking form of clinical disease. A five-stage classification system is presented.ConclusionsLongitudinal, full-fundus imaging of outer retinal atrophy in the rat eye identifies evolving, complex patterns of hyperfluorescent FAF that phenocopy aspects of disease.Translational RelevanceThis work provides a novel tool to assess hyperfluorescent FAF in association with progressive retinal atrophy, a therapeutic target in late AMD.

Correlation of Morphology and Function of Flecks Using Short-Wave Fundus Autofluorescence and Microperimetry in Patients With Stargardt Disease.

PurposeThe purpose of this study was to evaluate the functional relevance of longitudinal changes in hyperautofluorescent areas and flecks in Stargardt disease (STGD1) using short-wavelength autofluorescence (SW-AF) imaging.MethodsIn this prospective, longitudinal study, 31 patients with STGD1 (56 eyes) underwent microperimetry (MP) and SW-AF imaging twice in 3 to 5 years. A total of 760 MP test points were included in the statistical analysis based on stable fixation and accurate alignment of SW-AF and MP. Autofluorescence intensity was qualitatively assessed in all MP test points. Small circumscriptive hyperautofluorescent lesions were defined as flecks. Longitudinal imaging characteristics observed on SW-AF were classified into the following categories: appearing, disappearing, and stable flecks, stable hyperautofluorescent, and stable background autofluorescence. The relationship between SW-AF intensity changes and MP changes was analyzed using a linear mixed model corrected for baseline sensitivity.ResultsRetinal sensitivity declined most in locations without change in SW-AF intensity. Functional decline per year was significantly larger in flecks that disappeared (−0.72 ± 1.30 dB) compared to flecks that appeared (−0.34 ± 0.65 dB), if baseline sensitivity was high (≥10 dB; P < 0.01). The correlation between the change observed on SW-AF and the sensitivity change significantly depended on the sensitivity at baseline (P = 0.000).ConclusionsQualitative longitudinal assessment of SW-AF poorly reflected the retinal sensitivity loss observed over the course of 3 to 5 years.Translational RelevanceWhen aiming to assess treatment effect on lesion level, a multimodal end point including MP focused on hyperautofluorescent lesions appears essential but needs further studies on optimizing MP grids, eye-tracking systems, and alignment software.

Patchy hyperautofluorescence as a predictive factor for the recurrence of punctate inner choroidopathy.

To investigate baseline clinical and imaging factors that may correlate with risk of recurrence of punctate inner choroidopathy (PIC). In this retrospective observational study, charts and multimodal imaging of forty-five patients diagnosed with PIC during the active inflammatory phase were reviewed. MMI examinations, including fundus photography, shortwave fundus autofluorescence(SW-FAF), fluorescein angiography(FFA), indocyanine green angiography(ICGA), and spectral domain optical coherence tomography(SD-OCT_), were conducted to diagnose PIC, and MMI parameters at baseline were assessed as potential biomarkers indicating the recurrence of inflammation. Statistical analysis was performed to determine the clinical and imaging factors associated with recurrence of PIC. Among the 45 recruited patients, 18 (40 %) had at least one episode of recurrence during a mean follow-up period of 23.66 ± 12.65 months (range, 12-50 months). Best corrected visual acuity (BCVA) at the final visit during the follow-up was significantly different between the recurrence and nonrecurrence groups. Patchy hyperautofluorescence at baseline appeared in 77.78 % of the patients with recurrence, and the incidence of patchy hyperautofluorescence was significantly different between the patients with recurrence and those without recurrence (P＜0.001). Recurrence is not rare among PIC patients and leads to a worse visual acuity outcome. Patchy hyperautofluorescence at baseline is a risk factor for recurrence of PIC. Patchy hyperautofluorescent areas in PIC patients may indicate a need for close follow-up even though PIC-related inflammation regresses.

Multimodal structural disease progression of retinitis pigmentosa according to mode of inheritance

We analyze disease progression in retinitis pigmentosa (RP) according to mode of inheritance by quantifying the progressive decrease of the ellipsoid zone (EZ) line width on spectral domain optical coherence tomography (SD-OCT) and of the dimensions of the hyperautofluorescent ring on short-wave fundus autofluorescence (SW-FAF). In this retrospective study of 96 patients, average follow-up time was 3.2 ± 1.9 years. EZ line width declined at a rate of −123 ± 8 µm per year, while the horizontal diameter and ring area declined at rates of −131 ± 9 µm and −0.5 ± 0.05 mm2 per year, respectively. Disease progression was found to be slowest for autosomal dominant RP and fastest for X-linked RP, with autosomal recessive RP progression rates between those of adRP and XLRP. EZ line width and ring diameter rates of disease progression were significantly different between each mode of inheritance. By using EZ line width and horizontal diameter as parameters of disease progression, our results confirm that adRP is the slowest progressing form of RP while XLRP is the fastest. Furthermore, the reported rates can serve as benchmarks for investigators of future clinical trials for RP and its different modes of inheritance.

Spectrum of Disease Severity and Phenotype in Choroideremia Carriers

To characterize and bring awareness to the disease spectrum of female choroideremia patients, as severity can vary from mild to severe disease, comparable to that observed in male patients. Retrospective cohort study. Twelve female carriers of disease-causing variants in the CHM gene confirmed by molecular genetic sequencing were characterized clinically and imaged with short-wave fundus autofluorescence (SW-FAF), spectral-domain optical coherence tomography (OCT), and color fundus imaging. Twelve unrelated female patients with a clinical and genetic diagnosis of choroideremia carriers were included in this study. Disease severity among these phenotypes ranged from mild to severe, resembling the typical presentation of choroideremia in male patients. Mild disease presented with retinal pigment epithelium mottling, a patchy pattern of hypoautofluorescent speckles on SW-FAF, and intact retinal layers on spectral-domain OCT. Severe disease presented with widespread chorioretinal atrophy as shown by SW-FAF and spectral-domain OCT. Each of the identified genetic variants in CHM was predicted to be disease-causing according to insilico prediction software. Disease progression analysis of 4 patients with follow-up showed a decline in visual acuity for 2 patients, with progression observed on spectral-domain OCT in 1 of the patients. No significant disease progression on SW-FAF was observed for any of the patients. Female carriers of choroideremia can present with a wide range of clinical phenotypes and disease severity, from mild to severe disease, similar to male subjects. Symptomatic female subjects should be considered for current and upcoming gene replacement therapy clinical trials.

Imaging features of ultra-wide field fundus autofluorescence in multiple evanescent white dot syndrome

Objective To observe the imaging features of ultra-wide field short wave fundus autofluorescence (SW-FAF) in eyes with multiple evanescent white dot syndrome (MEWDS), and analysis the correspondence to conventional images. Methods It was a retrospective case series study. Thirteen patients (14 eyes) diagnosed with MEWDS were enrolled. There were 12 females and 1 male, aged from 22 to 57 years, mean age was 34.5 years. All the eyes underwent fundus color photography, optical coherence tomography (OCT) and ultra-wide field autofluorescence (FAF). Simultaneous fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed in 6 eyes. The characteristic changes of SW-FAF in studied eyes were observed and compared with the images of FFA and ICGA. All the eyes were followed up every 1 to 2 weeks, with an average of 16.7 weeks. The characteristic images of SW-FAF and corresponding OCT were studied during follow up. Results MEWDS presented with numerous multiple hyper-autofluorescent spots, sized from 50 - 500 μm, with a vague boundary in ultra-wide field SW-FAF. These spots located mainly at the peripapillary area and the posterior pole with a confluent pattern. The lesions extended to the mid-peripheral retina as well and became more scattered. The distribution of the hyper-autofluorescent lesions in SW-FAF corresponded roughly to that of the greyish-white spots seen in color photograph and the hyper-fluorescent spots detected by FFA. It was consistent with the distribution of hypo-fluorescent spots in late-phase ICGA as well. But the number of the spot showed in FAF is much more than that in FFA, and slightly less than that in ICGA. The OCT scans through the hyper-autofluorescent lesions in SW-FAF showed impairment of outer retina. After the recovery, the hyper-autofluorescent spots disappeared with the outer retina structure repaired completely. Conclusions MEWDS presented with numerous multiple hyper-autofluorescent spots which located mainly at the peripapillary area in ultra-wide field SW-FAF. The distribution of the hyper-autofluorescent lesions in SW-FAF corresponded roughly to color photograph, FFA and ICGA in late-phase. The OCT scans through the hyper-autofluorescent lesions in SW-FAF showed impairment of outer retina. Key words: Retinal diseases/diagnosis; Fluorescein angiography; Indocyanine green; Tomography, optical coherence; Diagnostic imaging

Diyabetik Makula Ödemi Olgularında Fundus Otoflöresans ile Spektral Optik Koherens Tomografi Bulguları Arasındaki İlişki

Objective: The aim of this study was to investigate the correlation between short-wave fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT) measures in patients with diabetic cystoid macular edema. Material and Methods: FAF and SD-OCT measurements were recorded from 123 eyes of 84 patients. The patients were grouped and compared according to their FAF grades as follows: grade 1 (group 1, n=27), grade 2 (group 2, n=27), grade 3 (group 3, n=32), and grade 4 (group 4, n=37). FAF graded manually by single grader. The groups were compared in terms of OCT findings (central macular thickness (CMT), total macular volume (TMV), and IS/OS band integrity) with FAF type (single lobule, multi-lobular or mixed) and FAF grade. Results: Group 1 and 2 patients primarily had single lobule FAF patterns, and groups 3 and 4 had multi-lobular and mixed FAF patterns (p<0.001). Difference between FAF grade and central macular thickness and inner and outer segment (IS/OS) band disruption were statistically significant (p<0.001). IS/OS band disruption was primarily observed in patients with multi-lobular and mixed FAF patterns (p<0.041). Conclusion: Increased FAF grade and a mixed FAF pattern have statistically significant relation with the IS/OS band disruption ratio.

Retinal structure in vitamin A deficiency as explored with multimodal imaging

To define the retinal structural abnormalities in a patient with vitamin A deficiency. The patient had a complete ophthalmic examination, electroretinography (ERG), short-wave fundus autofluorescence (SW-AF) and spectral domain optical coherence tomography (SD-OCT) imaging. Serum vitamin A levels were measured. A 63-year-old man with alcoholic cirrhosis, sclerosing cholangitis and chronic pancreatitis experienced blurred vision and nyctalopia for over a year. There was no family history of eye disorders or consanguinity. His best-corrected visual acuity was 20/20 in each eye; color vision as determined with Ishihara color plates was normal in each eye. Anterior segment examination was unremarkable. He was pseudophakic in both eyes. Standard ERGs showed non-detectable rod function, a cone-mediated dark-adapted response to the standard flash and borderline reduced cone function. Serum vitamin A levels were below 0.06 mg/L (normal 0.3-1.2 mg/L). Fundus examination revealed numerous round yellow-white lesions along the superior arcade and nasal to the optic nerve in both eyes. These lesions were hypoautofluorescent on SW-AF. SD-OCT cross sections demonstrated that they were focal disruptions distal to the ellipsoid band of the photoreceptors with hyperreflective images bulging up the ellipsoid and region. The retinal pigment epithelium and the inner retina appeared intact. Limited and gradual vitamin A supplementation for over a month (20 000 IU/day) led to a dramatic improvement in retinal function and to the resolution of the symptoms. The retinal lesions remained unchanged. Imaging of this patient with nyctalopia and severe rod dysfunction suggests that the retinal white lesions known to occur in vitamin A deficiency localize to the photoreceptor layer, particularly the outer segment. On OCT, they are reminiscent of lesions observed in genetic diseases with retinoid cycle dysfunction and of drusenoid subretinal deposits, an abnormality commonly associated with age-related macular degeneration.