Fundus Autofluorescence Patterns Research Articles

The Discrepancy Between Visual Acuity Decline and Foveal Involvement in Geographic Atrophy

To investigate the discrepancy between visual acuity (VA) decline and foveal involvement in geographic atrophy (GA) secondary to non-exudative age-related macular degeneration (AMD), and to explore how early retinal changes impact the progression of visual impairment. Retrospective, longitudinal cohort study. This study evaluated 80 eyes from 60 patients (mean age 74.2±10 years) with progressing non-neovascular AMD using blue-light fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT). The study monitored the onset of foveal involvement and analyzed VA changes over an average follow-up of 60±26.4 months, encompassing 785 observations. Mixed-effects models with natural splines assessed the effects of demographic and ocular characteristics on baseline VA and its rate of decline. Survival analyses compared the timing of anatomical changes with the most rapid functional declines, indicated by the highest first derivative of VA trajectories. Discrepancies between visual and anatomical changes were explored using generalized linear mixed-effects models. VA declined consistently by an average of 0.010 LogMAR per month (SE: 0.0003, p<0.001). The onset of foveal involvement significantly exacerbated this decline, adding an average loss of 0.15 LogMAR (SE: 0.02, p<0.001). Stabilization of VA typically occurred around 41 months post-foveal involvement. Significant factors associated with worse baseline VA were older age, female gender, unifocal GA morphology, and drusen-associated forms of GA (p<0.05). The most rapid declines in VA typically occurred about 9 months (IQR 0-27 months) prior to detectable subfoveal changes. The reticular FAF pattern (27/46 [59%] vs. 2/13 [15%], p=0.02) and smaller baseline GA lesions (p=0.01) were associated with faster deterioration preceding visible foveal damage. This study demonstrates that significant VA loss in GA can precede detectable foveal involvement, suggesting a window for early interventions to slow the progression of visual impairment. Identifying specific GA characteristics and FAF patterns as predictors of rapid VA decline supports the need for personalized treatment strategies to optimize outcomes for patients with non-exudative AMD.

Multicentric Longitudinal Prospective Study in a European Cohort of MYO7A Patients: Disease Course and Implications for Gene Therapy.

We investigated the natural history of retinal dystrophy owing to variants in the MYO7A gene. Fifty-three patients (mean age, 33.6 ± 16.7years) with Usher syndrome owing to biallelic, mostly pathogenic, variants in MYO7A underwent baseline and two annual follow-up visits. Best-corrected visual acuity (BCVA), semiautomatic kinetic visual field, full-field electroretinogram, color fundus imaging, microperimetry, spectral-domain optical coherence tomography, and fundus autofluorescence were assessed. At baseline, all patients presented with decreased BCVA (66.4 ± 17.9 Early Treatment Diabetic Retinopathy score and 59.5 ± 21.7 Early Treatment Diabetic Retinopathy score, in the better- and worse-seeing eyes, respectively), restricted semiautomatic kinetic visual field (III4e area, 3365.8 ± 4142.1°2; 4176.4 ± 4400.3°2) and decreased macular sensitivity (9.7 ± 9.9dB; 9.0 ± 10.2dB). Spectral-domain optical coherence tomography revealed reduced central macular thickness (259.6 ± 63.0µm; 250.7 ± 63.3µm) and narrowed ellipsoid zone band width (2807.5 ± 2374.6µm; 2615.5 ± 2370.4µm). Longitudinal analyses (50 patients) showed a significant decrease of BCVA in better-seeing eyes, whereas no changes were observed in worse-seeing eyes for any parameter. BCVA, semiautomatic kinetic visual field (III4e and V4e) and macular sensitivity were related significantly to age at baseline. Hyperautofluorescent foveal patch (16 eyes [31.4%]) and abnormal central hypoautofluorescence (9 eyes [17.6%]) were significantly associated with worse morphological and functional read-outs compared with the hyperautofluorescent ring pattern (22 eyes [43.1%]). Our European multicentric study offers the first prospective longitudinal analysis in one of the largest cohorts of MYO7A patients described to date, confirming the slow disease progression. More important, this study emphasizes the key role of fundus autofluorescence patterns in retinal impairment staging and advocates its adoption as an objective biomarker in patient selection for future gene therapy clinical trials.

Circular Perivascular Autofluorescence Pattern in Patients With Autoimmune Retinopathy.

Purpose: To report the characteristics and prevalence of a previously undescribed circular perivascular fundus autofluorescence (FAF) pattern in paraneoplastic and nonparaneoplastic autoimmune retinopathy. Methods: This retrospective case series used clinical and imaging data extracted from charts of patients with autoimmune retinopathy in whom FAF imaging was performed from the initial presentation to the last visit. Results: Six of 25 patients with autoimmune retinopathy and FAF imaging developed circular perivascular FAF changes. Three patients had paraneoplastic autoimmune retinopathy, and 3 had nonparaneoplastic autoimmune retinopathy. The lesions appeared a mean of 25 months after symptom onset; however, the timing varied from months to years and did not correlate with the overall disease course. The lesions were initially typically hyperautofluorescent and varied in progression, distribution, and quality. Optical coherence tomography showed hyperreflective subretinal deposits in the corresponding areas in most patients. Conclusions: To our knowledge, these are the first reported cases with this circular perivascular FAF pattern in nonparaneoplastic autoimmune retinopathy. This finding could also be a useful diagnostic imaging marker in some patients with autoimmune retinopathy.

Fundus Autofluorescence Patterns in Subretinal Hemorrhages Associated with Neovascular Age-Related Macular Degeneration

Introduction: Submacular hemorrhage (SMH) is a vision-threatening complication of neovascular age-related macular degeneration (AMD). The exact treatment scheme is not established yet. The aim of the current study was to describe surgical results and fundus autofluorescence (FAF) patterns after pars plana vitrectomy (ppV) + subretinal tissue plasminogen activator (tPA) + anti-vascular endothelial growth factor (VEGF) and intravitreal tPA + anti-VEGF + sulfur hexafluoride (SF6) tamponade and to compare them to intravitreal tPA + anti-VEGF + SF6 in the treatment of SMH in the course of AMD. Materials and Methods: We performed FAF imaging in patients with a previous SMH in the course of AMD with a duration of <60 days treated with vitrectomy with subretinal anti-VEGF and tPA and intravitreal anti-VEGF, tPA, and SF6 administration (group 1) or intravitreal tPA + anti-VEGF + SF6 (group 2). In all eyes, a throughout ophthalmic examination, fluorescein angiography, and spectral domain optical coherence tomography (SD-OCT) were done for diagnosis. SD-OCT was performed monthly during treatment. Results: Three FAF patterns were observed in both groups. Pattern one (normal autofluorescence) was observed in 5/18 in group one and 5/21 group two. Pattern two was observed in 6/18 in group one and 7/21 in group two. Pattern three was noted in 7/18 in group one and 5/21 in group two. Improvement in visual acuity was statistically significant for both groups: 0.01 Snellen (2.0 logMAR) to 0.11 Snellen (0.96 logMAR) in group one (p = 0.019) and 0.11 Snellen (0.96 logMAR) to 0.33 Snellen (0.48 logMAR) in group two (p = 0.0007). Central retinal thickness also decreased with statistical significance for both groups (p < 0.05). Conclusion: FAF patterns did not depend on the treatment used, but solely on the duration of SMH before treatment. SMH if not treated prompt enough might cause long-standing photoreceptor and retinal pigment epithelium defect, which is represented by hypo- and hyperautofluorescence. Performing a subretinal injection of tPA and anti-VEGF does not cause any defects associated with the injection site. That might be associated with previous local internal limiting membrane peeling, which reduces the injection pressure. Not only prompt treatment of SMH but also further continuation of anti-VEGF treatment is mandatory to maintain vision.

Retinal sensitivity and fundus autofluorescence in adult-onset foveomacular vitelliform dystrophy

The present study aimed to compare retinal sensitivity (RS) at each stage and to evaluate the relationship between RS and fundus autofluorescence (FAF) pattern in adult-onset foveomacular vitelliform dystrophy (AOFVD). We retrospectively reviewed 17 eyes of 13 patients with AOFVD. In addition to best-corrected visual acuity (VA), RS within the affected lesion and optical coherence tomography (OCT) measurements were carried out in each participant. All the examined eyes were classified into 4 stages and 3 FAF patterns. RS was superimposed on OCT fundus image and RS within the affected lesion was calculated in each eye. The relationships between visual functions (VA and RS within the affected lesion) and stages and also FAF patterns were analyzed using the linear mixed model. As a result, RS within the affected lesion was significantly associated with FAF pattern, but not with stage. In contrast, VA was correlated with neither stages nor FAF patterns. Our current result suggested that RS within the affected lesion was related to FAF patterns but this was not the case with VA in eyes with AOFVD, demonstrating the usefulness of measuring RS, not only VA, to comprehend the disease status in AOFVD.

Correlation Between Fundus Autofluorescence Pattern and Retinal Function on Microperimetry in Choroideremia.

In patients with choroideremia, it is not known how smooth and mottled patterns on short-wavelength fundus autofluorescence (AF) imaging relate to retinal function. A retrospective case-note review was undertaken on 190 patients with choroideremia at two specialist centers for retinal genetics. Twenty patients with both smooth and mottled zones on short-wavelength AF imaging and concurrent mesopic microperimetry assessments were included. Mean retinal sensitivities within the smooth and mottled zones were compared between choroideremia patients, and identical points on mesopic microperimetry collected from 12 age-matched controls. Longitudinal analyses were undertaken at 2 and 5years in a subset of patients. In patients with choroideremia, mean retinal sensitivities at baseline were significantly greater in the smooth zone (26.1 ± 2.0 dB) versus the mottled zone (20.5 ± 4.2 dB) (P < 0.0001). Mean retinal sensitivities at baseline were similar in the smooth zone between choroideremia patients and controls (P = 0.054) but significantly impaired in the mottled zone in choroideremia compared to controls (P < 0.0001). The rate of decline in total sensitivity over 5 years was not significant in either the smooth or mottled zone in a small subset of choroideremia patients (n = 7; P = 0.344). In choroideremia, retinal sensitivity as determined by microperimetry correlates with patterns on AF imaging: retinal function in the smooth zone, where the retinal pigment epithelium is anatomically preserved, is similar to controls, but retinal sensitivity in the mottled zone is impaired. Patterns on AF imaging may represent a novel, objective outcome measure for clinical trials in choroideremia as a surrogate for retinal function.

Acute zonal occult outer retinopathy misdiagnosed as giant cell arteritis: a challenging case

Background: Acute zonal occult outer retinopathy (AZOOR) is a rare autoimmune retinopathy that is challenging to diagnose and treat. It usually presents with subtle fundus changes and severe visual symptoms. Herein, we report a challenging case of AZOOR, emphasizing that multimodal imaging could be valuable in diagnosis and monitoring of treatment response.&#x0D; Case Presentation: A 53-year-old woman presented to the emergency department with a one-week history of subacute, severe, painless vision loss without photopsia in her right eye. Her best-corrected distance visual acuity was 20/800 in the right eye and 20/20 in the left eye. Slit-lamp examination findings were unremarkable, and intraocular pressure was normal in both eyes. Initially, fundus examination findings appeared normal; however, serum levels of inflammatory markers were elevated. Brain and orbital magnetic resonance imaging results were unremarkable. A relative afferent pupillary defect was present in subsequent follow-up examinations at the hospital. The patient initially received a diagnosis of posterior ischemic optic neuropathy secondary to occult giant cell arteritis, underwent steroid treatment, and was evaluated by rheumatology and neurology consultants. Both consultants concurred with the presumed diagnosis. Subsequent multimodal imaging in the ophthalmology clinic revealed a trizonal pattern of fundus autofluorescence. Corresponding to these areas, we noted a loss of the ellipsoid zone on optical coherence tomography, depression on multifocal electroretinogram, and scotoma on visual field testing. Accordingly, the diagnosis of AZOOR was made. The patient was referred back to the rheumatologist for initiation of steroid-sparing treatment, and methotrexate was administered. Five months after the initial presentation, the patient showed significant visual field improvement in both eyes.&#x0D; Conclusions: Eye care practitioners should consider AZOOR in the differential diagnosis of patients with subacute painless severe unilateral vision loss and unremarkable findings on fundus examination. Multimodal imaging could be valuable in diagnosis and monitoring of treatment response, as observed in the current case. Further studies with larger sample sizes are needed to confirm the value of multimodal imaging and the available management options for AZOOR.

Classification of fundus autofluorescence abnormal patterns in diabetic macular edema.

Patients with diabetic macular edema can develop fundus autofluorescence alterations; thus far, these alterations have been more widely studied with scanning or confocal laser systems. To describe and classify fundus autofluorescence abnormal patterns in patients with diabetic macular edema using the fundus autofluorescence system with a flash camera. Observational, retrospective, cross-sectional, descriptive study. Fundus autofluorescence digital images of non-comparative cases with untreated diabetic macular edema, obtained and stored with a flash camera system, were assessed. Inter-observer variability was evaluated. 37 eyes of 20 patients were included. Lens opacity was the most common cause of inadequate image quality. Five different fundus autofluorescence patterns were observed: decreased (13%), normal (40%), single-spot hyper-autofluorescent (17 %), multiple-spot hyper-autofluorescent (22 %) and plaque-like hyper-autofluorescent (8 %). The kappa coefficient was 0.906 (p = 0.000). Different fundus autofluorescence phenotypic patterns are observed with flash camera systems in patients with diabetic macular edema. A more accurate phenotypic classification could help establish prognostic factors for visual loss or for the design of clinical trials for diabetic macular edema.

Fundus autofluorescence pattern in different cases of cone inherited macular dystrophies

AbstractPurpose: To study fundus autofluorescence (FAF) with blue light excitation (488 nm) in different cases of cone inherited macular dystrophies an to assess differential characteristics.Methods: We studied different cone inherited retinal dystrophies due primary to ABCA4 mutation with blue FAF and correlate the findings with the clinical impairment. We compared with the findings in other mutations.Results: We presented 9 cases of Stargardt diseases with ABCA4 mutation with different blue FAF characteristics, from single macular impairment with an hypofluorescence, pattern, hyperreflective flecks around the central lesion or flecks extended outside the vascular branches. The extension of the flecks was no correlate with the degree of functional impairment. We compared with other cone dystrophies such as CRX mutation, with similar findings than the ones with only central impairment. Asymptomatic CRX mutation showed a hyperreflective central lesion.Conclusions: FAF is an essential tool to diagnose and follow‐up inherited retinal dystrophies with primary macular manifestation. Same mutation and clinical stage could present different patterns.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN PIGMENTED PARAVENOUS CHORIORETINAL ATROPHY.

To analyze the retino-choroidal vascular characteristics of patients affected by pigmented paravenous chorio-retinal atrophy by means of optical coherence tomography (OCT) angiography. This study was designed as an observational, cross-sectional case series. Multimodal imaging included fundus autofluorescence, structural OCT, and OCT angiography. The quantitative OCT angiography analyses included the calculation of the vessel density and choriocapillaris porosity. Overall, 12 patients (24 eyes) affected by pigmented paravenous chorio-retinal atrophy were recruited. Structural OCT of the areas involved by pigmented paravenous chorio-retinal atrophy as visualized on the fundus autofluorescence showed a complete ellipsoid zone and external limiting membrane absence, with thinning of ganglion cell complex, outer nuclear layer, and outer plexiform layer, but associated with the optical partial preservation of the retinal pigment epithelium. Optical coherence tomography angiography quantitative assessment of the retinal regions affected by PPRCA, as visualized by fundus autofluorescence, was characterized by normal vessel density at the level of superficial capillary plexus but significantly altered vessel density of deep capillary plexus and choriocapillaris, with higher choriocapillaris porosity. The presence of macular atrophy was significantly correlated with worse deep capillary plexus and choriocapillaris vessel density values. Furthermore, a statistically significant correlation between the fundus autofluorescence patterns and the retinal vascular status was found. Optical coherence tomography angiography quantitative analyses in pigmented paravenous chorio-retinal atrophy demonstrate a specific impairment at the level of the deep capillary plexus, which could in turn bring about a thinning of ganglion cell complex and outer nuclear layer. The alterations at the level of the choriocapillaris and the choroid, in general, could then represent a secondary effect.

Assessment of choroid thickness by swept‑source optical coherence tomography (SS-OCT) in patients with posterior uveitis

Background: This study aimed to measure the changes in choroid thickness using Swept-Source Optical Coherence Tomography (SS-OCT) after treatment of posterior uveitis along with changes in fundus auto-fluorescence pattern. Material and methods: This prospective observational cohort study was conducted from December 2018 to May 2020, in which 32 eyes of 20 patients presenting in the out-patient department with a clinical diagnosis of posterior uveitis were enrolled. Best-corrected visual acuity (BCVA) by Snellen chart, intraocular pressure (IOP) Measurement using a non-contact tonometer, choroidal thickness by SS-OCT, and fundus imaging by Fundus Autofluorescence was done. All tests were done at baseline, first follow-up of 2 ± 1 weeks and the second follow-up of 6 ± 2 weeks. Data was compiled and analyzed. Results: The mean age of patients was 31 ± 6.9 years with M:F of 3:1. During the second follow-up, with the healing of the lesions, there was a significant reduction in the choroidal thickness at all levels by SS-OCT (p &lt; 0.05), with significant improvement in BCVA (0.05 vs. 0.14 vs. 0.31, p &lt; 0.05). IOP increased significantly at the first follow-up to 17.31 from baseline (16.25) (p = 0.032). However, the rise at the second follow-up was not significant (17.03 vs. 16.25 at baseline, p = 0.15). On fundus autofluorescence, normal autofluorescence and hypofluorescence increased at the second follow-up of 6 weeks (p &lt; 0.0001) Conclusion: SS-OCT showed a significant decrease in the choroidal thickness at all levels during the follow-ups. The healing of the posterior uveitis lesions and fundus autofluorescence became normal simultaneously.

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.

Progression of age-related macular degeneration in eyes with abnormal fundus autofluorescence in a Japanese population: JFAM study report 3.

PurposeTo evaluate the progression of early age-related macular degeneration to neovascular age-related macular degeneration (nAMD), and identify the abnormal fundus autofluorescence (FAF) patterns and markers of choroidal neovascularization (CNV) in fellow eyes of patients with unilateral nAMD.MethodsSixty-six patients with unilateral nAMD who developed abnormal FAF in the fellow eyes were enrolled in this multicenter, prospective, observational study, and followed-up for 5 years. FAF images on Heidelberg Retina Angiogram Digital Angiography System (HRA) or HRA2 were classified into eight patterns based on the International Fundus Autofluorescence Classification Group system. The patients in which the fellow eyes progressed to advanced nAMD, including those who did not develop nAMD, were assessed based on the following factors: baseline FAF patterns, age, sex, visual acuity, drusen, retinal pigmentation, baseline retinal sensitivity, family history, smoking, supplement intake, hypertension, body mass index, and hematological parameters.ResultsOf the 66 patients, 20 dropped out of the study. Of the remaining 46 patients, 14 (30.42%, male: 9, female: 5) progressed to nAMD during the 5-year follow-up. The most common (50% eyes) FAF pattern in the fellow eyes was the patchy pattern. According to the univariate analysis, CNV development was significantly associated with age, supplement intake, and low-density lipoprotein levels (p<0.05). Multivariable analysis revealed that patients who showed non-compliance with the supplement intake were more likely to develop nAMD (p<0.05). No significant association was found between the patchy pattern and CNV development (p = 0.86).ConclusionThe fellow eyes (with abnormal FAF) of patients with unilateral nAMD may progress from early to advanced nAMD. However, no FAF pattern was found that predicted progression in nAMD.

Evaluation of fundus autofluorescence patterns in patients with central serous chorioretinopathy - A prospective, observational study

Evaluation of fundus autofluorescence patterns in patients with central serous chorioretinopathy - A prospective, observational study

ACUTE IDIOPATHIC MACULOPATHY: A Proposed Disease Staging Based on Multimodal Imaging.

To describe the clinical course and the multimodal imaging of acute idiopathic maculopathy. Medical records and multimodal imaging including color fundus photography, optical coherence tomography, and fundus autofluorescence were retrospectively reviewed. Recognition of the fundus autofluorescence patterns and their relationship with the disease duration, best-corrected visual acuity, and optical coherence tomography features represented the main outcome measures. Seventeen eyes of 16 patients (7 women; mean age 29.9 years) with a mean follow-up of 23.9 months were included. The mean best-corrected visual acuity at presentation was 0.63 ± 0.54 logarithm of the minimum angle of resolution (Snellen equivalent, 20/85). All but one patient had the best-corrected visual acuity recovery to 20/20. Four sequential patterns of fundus autofluorescence corresponding to 4 proposed stages of disease were observed. Patterns 1 (central hypoautofluorescence with surrounding hyperautofluorescence) and 2 (stippled hyperautofluorescence and hypoautofluorescence) were found at presentation. Patterns 3 (central hyperautofluorescence surrounded by hypoautofluorescence) and 4 (hypoautofluorescence) were observed during the disease course and/or at the last follow-up visit. Duration of the disease was significantly different between patterns at baseline and last visit. Pattern 1 significantly related to the presence of subretinal detachment (Fisher's exact test; P =0.003) on optical coherence tomography in comparison with Pattern 2. Pattern 4 showed unique homogeneously decreased autofluorescence with corresponding attenuation of retinal pigment epithelium and restored outer retinal layers on optical coherence tomography. A sequential disease staging based on multimodal imaging for acute idiopathic maculopathy is proposed. The recognition of the observed imaging patterns may help clinicians in the correct diagnosis and patient counseling.

X-Linked Retinoschisis: Deep Phenotyping and Genetic Characterization

To examine the genetic and clinical features in children and adults with X-linked retinoschisis (XLRS). Single-center consecutive, retrospective, observational study. Adults and children with molecularly confirmed XLRS followed up between 1999 and2020. Analysis of genetic, clinical, and retinal imaging findings, including OCT and fundus autofluorescence (FAF), cross-sectionally and longitudinally, was performed. RS1, variants, type of variants and phenotype correlations, ageof onset, complications rates and types, fundoscopy findings,OCT metrics, FAF patterns,correlations including between best corrected visual acuity (BCVA) and age, and OCT characteristics. One hundred thirty-two male patients were identified harboring 66 retinoschisin 1 variants, with 7 being novel. The mean age at onset was 16.5 years (range, 0-58 years). Seventy-one patients (71/75 [94.7%]) were symptomatic at presentation; all had decreased best-corrected visual acuity (BCVA). Funduscopy findings were symmetric in 104 patients (104/108 [96.3%]), with the most common finding being macular schisis (82.4%), whereas peripheral retinoschisis was present in 38.9% and macular atrophy was present in 11.1%. Twenty patients (18.5%) demonstrated complications (vitreous hemorrhage, retinal detachment, or both). Mean BCVA was 0.65 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/89) in the right eye and 0.64 logMAR (Snellen equivalent, 20/87) in the left eye. Mean BCVA change over a mean interval of 6.7 years was 0.04 and 0.01 logMAR for right and left eyes, respectively. A normal FAF pattern was identified in 16 of 106 eyes (15.1%); 45 eyes (42.5%) showed a spoke-wheel pattern, 13 eyes (12.3%) showed foveal hyperautofluorescence, and 18 eyes (17.0%) showed a central reduction in signal. In total, 14 patients demonstrated evidence of progression on FAF over time. On OCT, foveoschisis was observed in 172 eyes (172/215 [80%]), parafoveal schisis was observed in 171 eyes (171/215 [79.5%]), and foveal atrophy was observed in 44 eyes (44/215 [20.5%]). Cystoid changes were localized to the inner nuclear layer (172/181 eyes [95%]), the outer nuclear layer (97/181 [53.6%]), and the ganglion cell layer (92/181 [50.8%]). Null variants were associated with worse final BCVA and aforementioned complications. X-linked retinoschisis is highly phenotypically variable, but with relative foveal and BCVA preservation until late adulthood, allowing more accurate prognostication. The slowly (often minimally) progressive disease course may pose a challenge in identification of early end points for therapeutic trials aimed at altering the kinetics of degeneration.

Fundus autofluorescence and optical coherence tomography biomarkers associated with the progression of geographic atrophy secondary to age-related macular degeneration.

To investigate the impact of qualitatively graded and deep learning quantified imaging biomarkers on growth of geographic atrophy (GA) secondary to age-related macular degeneration. This prospective study included 1062 visits of 181 eyes of 100 patients with GA. Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) images were acquired at each visit. Hyperreflective foci (HRF) were quantitatively assessed in SD-OCT volumes using a validated deep learning algorithm. FAF images were graded for FAF patterns, subretinal drusenoid deposits (SDD), GA lesion configuration and atrophy enlargement. Linear mixed models were calculated to investigate associations between all parameters and GA progression. FAF patterns were significantly associated with GA progression (p < 0.001). SDD was associated with faster GA growth (p = 0.005). Eyes with higher HRF concentrations showed a trend towards faster GA progression (p = 0.072) and revealed a significant impact on GA enlargement in interaction with FAF patterns (p = 0.01). The fellow eye status had no significant effect on lesion enlargement (p > 0.05). The diffuse-trickling FAF pattern exhibited significantly higher HRF concentrations than any other pattern (p < 0.001). Among a wide range of investigated biomarkers, SDD and FAF patterns, particularly in interaction with HRF, significantly impact GA progression. Fully automated quantification of retinal imaging biomarkers such as HRF is both reliable and merited as HRF are indicators of retinal pigment epithelium dysmorphia, a central pathogenetic mechanism in GA. Identifying disease markers using the combination of FAF and SD-OCT is of high prognostic value and facilitates individualized patient management in a clinical setting.

Disease expression caused by different variants in the BEST1 gene: genotype and phenotype findings in bestrophinopathies.

Purpose:To analyse the spectrum of clinical features and molecular genetic data in a series of patients carrying likely disease-associated variants in the BEST1 gene.Methods:Retrospective observational analysis of clinical data extracted from the medical records of visual function, multimodal imaging and electrophysiology of 62 eyes of 31 patients. Molecular genetic analysis was performed by means of panel-based NGS or Sanger sequencing.Results:The spectrum of variants in the BEST1 gene comprised 19 different variants and three of which are novel. Fundus photographs and OCT images allowed categorization of 52 eyes as Best vitelliform macular dystrophy (BVMD) with stages 1 to 5 and 10 eyes with autosomal recessive bestrophinopathy (ARB), with more severe phenotype. One patient was shown to be heterozygous for a variant, which has so far been described only in ARB, but this patient had the BVMD phenotype. There was no significant progression of the visual acuity during the follow-up period of 5 years both in BVMD and ARB. The most prevalent pattern of fundus autofluorescence (FAF) in BVMD was ‘patchy’. There were diverse visual field defects in static automated perimetry (SAP) depending on the stage. The Arden ratio was significantly lower in ARB patients and in eyes with stage 5 of BVMD.Conclusions:The genotype does not always predict the phenotype in patients with BVMD and ARB; however, having two mutations in the BEST1 gene causes a more severephenotype. FAFhelped to distinguish ARB from BVMD. Most of the observed eyesdidnotprogressfunctionallyduringthefollow-up.ARBandtheatrophicstageof BVMD as the disease end-stage had the worst visual functions and EOG results.

Fundus autofluorescence in retinal disorders

Background Fundus autofluorescence (FAF) is a noninvasive, rapid, and potentially useful imaging modality that continues to evolve. It reflects metabolic changes at the level of retinal pigment epithelium/photoreceptor complex and variation of fluorescence derived from lipofuscin and thus provides an assay of retinal and retinal pigment epithelium function. Aim Demonstration of the technique, concept, and clinical value of FAF. Patients and methods This study was performed on 63 eyes of 41 patients from May 2016 to May 2017 with various retinal diseases (age-related macular degeneration, macular dystrophy, central serous retinopathy) using digital fundus camera TRC-NW8F Plus Topcon with special filter (Spaide filter). Abnormalities in images of FAF were analyzed and correlated with the corresponding alteration in fluorescein angiography and optical coherence tomography findings. Results A broad range of characteristic FAF patterns were observed. Distribution and variation with disease imply that the fluorescence is derived from lipofuscin in the pigment epithelium. Autofluorescence is shown to be abnormally high in certain inherited diseases, and low in the presence of retinal atrophy. Conclusion FAF imaging constitutes a useful additive tool in the diagnosis and follow-up of various retinal diseases and may detect abnormalities beyond those detected on funduscopic examination.

Fundus autofluorescence in premature infants

To describe fundus autofluorescence (FAF) patterns in premature infants and to determine whether FAF increases gradually with increasing post-gestational age. This was a cross-sectional, observational and descriptive case series. FAF images were obtained from patients screened for Retinopathy of Prematurity. The presence of the following hypo-autofluorescence areas/structures was graded and ranked: macular pigment (foveal centre), optic nerve head, peripapillary vessels/vascular arcade (PP/VA), and equatorial vessels (EqV). Ranks were attributed to the number of structures visualized from the posterior pole towards the periphery. The rank of FAF could then be analysed by Spearman’s correlation against age. Additionally, patients were divided by age into group 1 (< 40 weeks of corrected gestational age (WCGA)) and group 2 (> 40 WCGA). Differences between groups were tested with the Mann–Whitney U test. Thirteen patients were analysed. The mean WCGA at examination was 47.85 weeks. Spearman’s correlation showed a strong positive correlation (r = 0.714) (P = 0.006) of FAF and WCGA. The Mann–Whitney U test revealed that the PP/VA and EqV were significantly more visible at > 40 WCGA than at < 40 WCGA (8.0 [P = 0.016] and 7.5 [P = 0.03], respectively). Patterns of FAF are described for the first time in premature infants. FAF increases gradually with age and centrifugally from the posterior pole towards the equator in premature infants.