Abnormal Fundus Autofluorescence Research Articles

DISCREPANCY BETWEEN FUNDUS AUTOFLUORESCENCE ABNORMALITY AND VISUAL FIELD LOSS IN BIETTI CRYSTALLINE DYSTROPHY.

The aim of this study was to explore the potential benefits of retinal pigment epithelium replacement therapy in patients with Bietti crystalline dystrophy (BCD) by assessing the disease pathology with the distinctive relationship between fundus autofluorescence (FAF) abnormality and visual field defect. Sixteen eyes from 16 patients with BCD and 16 eyes from 16 patients with RHO-associated retinitis pigmentosa were included. Fundus autofluorescence, optical coherence tomography, and Goldmann perimetry results were retrospectively reviewed and assessed using image analyses. In patients with BCD, the FAF abnormality area was not correlated with the overall visual field defect area and median overall visual field defect area (57.5%) was smaller than FAF abnormality area (98.5%). By contrast, the ellipsoid zone width was significantly correlated with the central visual field area (r = 0.806, P < 0.001). In patients with RHO-associated retinitis pigmentosa, the FAF abnormality area and ellipsoid zone width were significantly correlated with the overall visual field defect area (r = 0.833, P < 0.001) and central visual field area (r = 0.887, P < 0.001), respectively. The FAF abnormality shown in patients with BCD involves retinal pigment epithelium degeneration without complete loss of photoreceptors or visual function. These results suggest that patients with BCD are good candidates for retinal pigment epithelium replacement therapy for preservation of residual visual function.

Case series: Fundus autofluorescence abnormalities in a family of ocular albinism carriers.

Carriers of ocular albinism demonstrate signs of retinal mosaicism with unique features on fundus autofluorescence testing, which differentiate this condition from other x-linked retinal disorders in carrier patients. Distinctive findings include a mud-splattered fundus with peripheral hyperpigmented streaks, which correlate with areas of hyperautofluorescence and hypoautofluorescence. This is the first reported case series of a family that demonstrates diagnostic retinal and fundus autofluorescence abnormalities related to retinal mosaicism in three sisters who were unaware they were carriers of ocular albinism type 1. Multimodal imaging, electrodiagnostic testing, and genetic testing can be used to confirm the diagnosis and differentiate this clinical presentation from other sight-threatening hereditary retinal diseases. Three sisters, aged 21, 17, and 13 years, were referred to determine the cause of abnormal retinal pigmentation. All presented with normal vision, and anterior segment examination was unremarkable without iris transillumination. They denied family history of ocular disease. Fundus examination of all three sisters revealed a mud-splattered pattern of pigmentation in the posterior pole and radial pigmentary streaks. Fundus autofluorescence showed a pattern of hyperautofluorescence and hypoautofluorescence corresponding to this pigmentary pattern. Spectral domain optical coherence tomography, electro-oculogram, and electroretinogram were normal in all three sisters. Genetic testing of their father, who was unaware of any disorder, tested positive for ocular albinism. Ocular albinism carriers have abnormal retinal pigmentation in a characteristic pattern. Fundus autofluorescence shows a correlative pattern that can confirm carrier status of ocular albinism in individuals unaware of their status and rule out other retinal degenerations.

TOWARD AN IMAGING-CENTRIC DEFINITION OF NONPARANEOPLASTIC AUTOIMMUNE RETINOPATHY.

To explore characteristic imaging features of nonparaneoplastic autoimmune retinopathy (npAIR) to augment diagnostic criteria. This is a retrospective cohort study of patients with npAIR evaluated at the Emory Eye Center between 2013 and 2019. Multimodal fundus images were evaluated to characterize the evolution of the disease. Twenty-one eyes of 12 patients were classified as having npAIR. Five patients (42%) were female, with median (range) age of 59 years (45-85 years). Median baseline visual acuity was 20/30 (20/20 to hand motions). Disease was asymmetric in 11 patients (92%). Common imaging findings included absence of bone spicules (86% of affected eyes), presence of attenuated vessels (86%), and speckled hypoautofluorescence in perimacular and perivenular regions. Three eyes were noted to present early with subtle splotchy fundus autofluorescence abnormality, ultimately developing characteristic speckled perimacular hypoautofluorescence. On optical coherence tomography, 18 eyes (86%) had loss of outer retinal bands with relative foveal sparing and a tapered transition zone. Many eyes with npAIR exhibit a subacute, asymmetric, generalized photoreceptor degeneration featuring outer retinal atrophy with relative foveal sparing, retinal vascular attenuation, absence of bone spicules, and speckled hypoautofluorescence often in a perimacular and perivenular distribution. Findings of this study augment diagnostic criteria to improve specificity and accessibility of testing for npAIR.

Fundus autofluorescence in uveitis: Meeting an old friend

Fundus autofluorescence (FAF) represents a relatively new imaging modality that has been investigated in a variety of uveitic disease processes. FAF relies on the presence of innate fluorophores within ocular tissues, which can be induced to emit light when stimulated with specific frequencies of light.Autofluorescence in the RPE depends on the outer segment renewal and can be affected by the RPE's ability to clear lipofuscin. Hence, an increased autofluorescence is seen with RPE dysfunction and a decreased autofluorescence is seen with loss of photorecptors or the RPE.Abnormal autofluorescence patterns have been described in a number of infectious and non‐infectious uveitides. Most reports of abnormal FAF in patients with uveitis belong to the spectrum of white‐dot‐syndromes. In the present course we will review the main autofluorescence abnormalities in disease like Serpiginous and Serpiginous‐like choroiditis, multifocal choroiditis, punctate inner choroiditis, multiple evanescent white dot syndrome and AZOOR. The recognition of theses abnormalities (in combination with other imaging techniques like optical coherence tomography and optical coherence tomography‐angiography) is extremely helpful for understanding their pathogenesis and monitoring the inflammatory activity.

MULTIZONAL OUTER RETINOPATHY AND RETINAL PIGMENT EPITHELIOPATHY (MORR): A Newly Recognized Entity or an Unusual Variant of AZOOR?

To describe specific clinical, multimodal imaging, and natural history features of an unusual variant of acute zonal occult outer retinopathy. Retrospective, observational, longitudinal, multicenter case series. Patients exhibiting this unusual clinical condition among cases previously diagnosed with acute zonal occult outer retinopathy were included. Multimodal imaging, laboratory evaluations, and genetic testing for inherited retinal diseases were reviewed. Twenty eyes from 10 patients (8 females and 2 males) with a mean age of 54.1 ± 13.3 years (range, 38-71 years) were included. The mean follow-up duration was 13.1 ± 5.3 years (range, 8-23 years). Presenting symptoms were bilateral in 7 patients (85% of eyes) and included scotomata and photopsia. All patients had bilateral lesions at presentation involving the peripapillary and far peripheral retina. Baseline optical coherence tomography showed alteration of the retinal pigment epithelium and photoreceptor layers corresponding to zonal areas of fundus autofluorescence abnormalities. Centrifugal and centripetal progression of the peripapillary and far-peripheral lesions, respectively, occurred over the follow-up, resulting in areas of complete outer retinal and retinal pigment epithelium atrophy. Initial alteration of photoreceptors and retinal pigment epithelium and a stereotypical natural course that includes involvement of the far retinal periphery, characterize this unusual condition. It may represent a variant of acute zonal occult outer retinopathy or may be a new entity. We suggest to call it multizonal outer retinopathy and retinal pigment epitheliopathy .

Deep phenotypic characterization of the retinal dystrophy in patients with RNU4ATAC-associated Roifman syndrome.

To characterize the retinal phenotype in RNU4ATAC-associated Roifman syndrome. Ten patients (including 8 males) with molecularly confirmed Roifman syndrome underwent detailed ophthalmologic evaluation including fundus imaging, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (SD-OCT), and electroretinography (ERG). Six patients had follow-up eye exams. All patients also underwent comprehensive examination for features of extra-retinal Roifman syndrome. All patients had biallelic RNU4ATAC variants. Nyctalopia was common (7/10). Visual acuity at presentation ranged from 20/20 to 20/200 (Age Range: 5-41 years). Retinal exam revealed features of generalized retinopathy with mid-peripheral pigment epithelial changes. A para or peri-foveal ring of hyper-autofluorescence was the commonest FAF abnormality noted (6/8). The SD-OCT demonstrated relative preservation of the foveal ellipsoid zone in six cases; associated features included cystoid changes (5/10) and posterior staphyloma (3/10). The ERG was abnormal in all patients; nine showed generalized rod-cone dystrophy, whilst one patient with sectoral retinal involvement only had isolated rod dystrophy (20 years old). On follow-up examination (Mean duration: 8.16 years), progressive loss of visual acuity (2/6), mid-peripheral retinal atrophy (3/6) or shortening of ellipsoid zone width (1/6) were observed. This study has characterized the retinal phenotype in RNU4ATAC-associated Roifman syndrome. Retinal involvement is universal, early-onset, and overall, the retinal and FAF features are consistent with rod-cone degeneration that is slowly progressive over time. The sub-foveal retinal ultrastructure is relatively preserved in majority of patients. Phenotypic variability independent of age exists, and more study of allelic- and sex-based determinants of disease severity are necessary.

Fundus autofluorescence abnormalities can predict fluorescein angiography abnormalities in patients with chronic central serous chorioretinopathy.

This study is to assess the possible correlation between findings on fundus autofluorescence (FAF) and fluorescein angiography (FA) in patients with chronic central serous chorioretinopathy (cCSC). This multicentre retrospective cohort study included 71 cCSC patients (92 eyes) with at least 6months of follow-up, who had a FAF-FA imaging discrepancy larger than 0.5 optic disc diameters in size in the corresponding areas of hyperfluorescent abnormalities. A comparison was performed between progression in size of areas of hyperautofluorescent retinal pigment epithelium (RPE) abnormalities on FAF (HF-FAF) and the hyperfluorescent areas on FA (HF-FA) at first visit and last visit. The possible correlations were estimated between FAF-FA discrepancy and disease characteristics. The median area of HF-FAF at first visit was 7.48mm2 (1.41-27.9). The median area of HF-FA at first visit and last visit was 2.40mm2 (0.02-17.27) and 5.22mm2 (0.53-25.62), respectively. FAF-FA discrepancy was associated with follow-up duration and the area of HF-FAF at first visit. A mathematical algorithm for grading FAF-FA discrepancy in time was suggested, which predicted the enlargement of hyperfluorescent RPE abnormalities on FA in 82.6% of cases. There is a statistically significant relationship between the areas of HF-FAF and HF-FA in cCSC patients with FAF-FA imaging discrepancy at first presentation. Long-term changes in RPE alterations in cCSC on FA can be predicted based on baseline HF-FAF and follow-up duration.

Retinal Pigment Epithelial Abnormality and Choroidal Large Vascular Flow Imbalance Are Associated with Choriocapillaris Flow Deficits in Age-Related Macular Degeneration in Fellow Eyes

Choriocapillaris flow deficits detected on optical coherence tomography angiographs were retrospectively analyzed. In 38 age-related macular degeneration (AMD) fellow eyes, without fundus findings (26 men, 71.7 ± 1.9 years old), and 22 control eyes (11 men, 69.4 ± 1.8), the choriocapillaris flow area (CCFA) ratio and coefficient of variation (CV) of the CCFA ratio (which represented the heterogeneity of the ratio), negatively and positively correlated with age (all p < 0.01), respectively. Moreover, the respective mean values were lower (p = 0.0031) and greater (p = 0.002) in AMD fellow eyes than in the control eyes. The high-risk condition of AMD fellow eyes was defined by a CCFA ratio <58.5%, and the CV of the CCFA ratio ≥0.165 (odds ratio (OR), 5.408; 95% confidence interval (CI): 1.117-21.118, p = 0.035, after adjusting for age and sex) was related to the presence of fundus autofluorescence abnormality (OR, 16.440; 95% CI, 1.262-214.240; p = 0.033) and asymmetrically dilated choroidal large vasculature (OR, 4.176; 95% CI, 1.057-16.503; p = 0.042), after adjusting for age and sex. The presence of fundus autofluorescence abnormality indicated a retinal pigment epithelium (RPE) abnormality. The RPE volume was reduced in the latter eye group, particularly in the thinner choroidal vasculature. In addition to aging, RPE abnormality and choroidal large vascular flow imbalances were associated with exacerbated heterogeneous choriocapillaris flow deficits in AMD fellow eyes without macular neovascularization.

Abnormal Fundus Autofluorescence in Eyes with Morquio Syndrome

Abnormal Fundus Autofluorescence in Eyes with Morquio Syndrome

Association of Fundus Autofluorescence Abnormalities and Pachydrusen in Central Serous Chorioretinopathy and Polypoidal Choroidal Vasculopathy.

A specific form of drusen, known as pachydrusen, has been demonstrated to be associated with pachychoroid eye diseases, such as central serous chorioretinopathy (CSC) and polypoidal choroidal vasculopathy (PCV). These pachydrusen have been found in up to 50% of eyes with CSC and PCV and may affect the disease progression and treatment response. This study aims to investigate the association between pachydrusen and changes in fundus autofluorescence (FAF) in eyes with CSC and PCV. A total of 65 CSC patients and 32 PCV patients were evaluated. Pachydrusen were detected using both color fundus photography and spectral-domain optical coherence tomography. The relationships between pachydrusen and FAF changes were then investigated. The prevalence of pachydrusen in CSC and PCV eyes was 16.7% and 61.8%, respectively. The mean age of patients with pachydrusen was significantly older than those without pachydrusen (CSC: 56.3 vs. 45.0 years, p < 0.001; PCV: 68.8 vs. 59.5 years, p < 0.001). No significant difference was found in the mean subfoveal choroidal thickness between eyes with or without pachydrusen. Eyes with pachydrusen were significantly associated with more extensive FAF changes in both CSC and PCV (p < 0.001 and p = 0.037, respectively). The study demonstrated that pachydrusen are more prevalent in PCV than CSC. Increasing age and more extensive abnormalities in FAF are associated with the presence of pachydrusen, suggesting that dysfunction of retinal pigment epithelial cells is associated with pachydrusen.

RAAV-mediated over-expression of acid ceramidase prevents retinopathy in a mouse model of Farber lipogranulomatosis.

Farber disease (FD) is a rare monogenic lysosomal storage disorder caused by mutations in ASAH1 that results in a deficiency of acid ceramidase (ACDase) activity and the abnormal systemic accumulation of ceramide species, leading to multi-system organ failure involving neurological decline and retinopathy. Here we describe the effects of rAAV-mediated ASAH1 over-expression on the progression of retinopathy in a mouse model of FD (Asah1P361R/P361R) and its littermate controls (Asah1+/+ and Asah1+/P361R). Using a combination of non-invasive multimodal imaging, electrophysiology, post-mortem histology and mass spectrometry we demonstrate that ASAH1 over-expression significantly reduces central retinal thickening, ceramide accumulation, macrophage activation and limits fundus hyper-reflectivity and auto-fluorescence in FD mice, indicating rAAV-mediated over-expression of biologically active ACDase protein is able to rescue the anatomical retinal phenotype of Farber disease. Unexpectedly, ACDase over-expression in Asah1+/+ and Asah1+/P361R control eyes was observed to induce abnormal fundus hyper-reflectivity, auto-fluorescence and retinal thickening that closely resembles a FD phenotype. This study represents the first evidence of a gene therapy for Farber disease-related retinopathy. Importantly, the described gene therapy approach could be used to preserve vision in FD patients synergistically with broader enzyme replacement strategies aimed at preserving life.

Redefining the Spectrum of Pentosan Polysulfate Retinopathy: Multimodal Imaging Findings from a Cross-Sectional Screening Study

There is growing evidence of a direct association between pentosan polysulfate (PPS) therapy and the development of macular changes. Using standardized visual acuity (VA) testing and multimodal imaging, we investigated the impact of PPS therapy on vision and described an expanded spectrum of imaging findings among PPS users. Cross-sectional screening study. Thirty-nine patients who were current or recent users of PPS. The participants underwent a brief eye examination and answered a comprehensive medical and ophthalmic history questionnaire. Color fundus photography, fundus autofluorescence (FAF), and spectral-domain OCT (SD-OCT) were performed. The images were evaluated by expert graders at Wisconsin Reading Center. Abnormalities were categorized as definite toxicity (DT) if seen on both FAF and SD-OCT and as questionable toxicity (QT) if seen on either FAF or SD-OCT. ETDRS and Snellen VA, the dosage and duration of PPS exposure, and the prevalence of retinal toxicity on imaging. The mean ETDRS and Snellen VA of the study cohort were 85 letters and 20/22, respectively. The mean PPS daily dose was 282 mg (range, 88-400 mg), whereas the mean cumulative dose was 915 g (range, 19-3650 g) over a mean period of 8.8 years (range, 2 months-25 years). There was evidence of retinopathy in 41% of the eyes; DT was identified in 24 eyes (31%) and QT in 8 eyes (10%). Retinal pigment epithelium (RPE) abnormalities (thickening or thinning or both) were present in all eyes with DT. Retinal pigment epithelium atrophy was seen in 7 eyes (9%). In addition to well-established findings, the unique SD-OCT features of this cohort included interdigitation zone abnormalities and the presence of a flying saucer-type defect. Fundus autofluorescence abnormalities were seen in 24 eyes (30.8%), with 20 (66.7%) of these exhibiting abnormalities located outside the central subfield and extending beyond the arcades. Findings from the masked grading of multimodal imaging at a centralized reading center suggest a wider phenotypic spectrum of structural abnormalities among patients taking PPS. Macular changes selectively involve the RPE and outer retina, with a range of findings often seen beyond the arcades. The subtle and atypical findings in this cohort should prompt clinicians to consider lowering the threshold for diagnosing PPS retinopathy.

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.

OCULAR CHANGES IN PATIENTS ON LONG TREATMENT WITH HYDROXYCHLOROQUINE

Introduction: To study the ocular changes in patients on long term treatment with Hydroxychloroquine (HCQ); and detect means for early detection of toxicity.Methods: We conducted a cross-sectional observational study at a tertiary care hospital, in which 100 patients, male and female, aged 35 years or more, taking HCQ for 5 years or more were included. Patients with any known ocular or systemic diseases were not included. Indication, dosage, duration and cumulative dose of HCQ intake were recorded. History of ocular symptoms, visual acuity, colour vision, complete ophthalmic examination, visual field using Amsler grid and 10-2 Humphrey’s automated fields (HVF), Spectral Domain Optical Coherence Tomography (SD-OCT), colour fundus photography, fundus fluorescein angiography (FFA) and fundus autofluorescence (FAF) were recorded. The data was analyzed using descriptive and inferential analysis.Result: 15% of the study population showed signs of HCQ related ocular toxicity. 17%, 21% and 10% patients had abnormal SD-OCT, HVF and FAF findings respectively.Conclusion: HCQ related ocular toxicity has been found in patients in the absence of symptoms. Objective tests like HVF, SD- OCT and FAF were more useful in early detection of toxicity than subjective tests such as Amsler grid, colour vision and FFA.

Frequency and risk factors for hydroxychloroquine retinopathy among patients with systemic lupus erythematosus

BackgroundHydroxychloroquine (HCQ) is an antimalarial drug, recently used in COVID-19 treatment. Also it is considered over many years the cornerstone in treating systemic lupus erythematosus (SLE) in adults and children. The incidence of retinal affection and retinal toxicity from hydroxychloroquine is rare, but even after the HCQ is stopped, loss of vision may not be reversible and may continue to progress. Fundus autofluorescence (FAF) is one of the screening methods recommended by AAO used for the diagnosis of hydroxychloroquine retinopathy. Our aim is to detect early HCQ-induced retinopathy among SLE patients and the risk factors for its development by using fundus autofluorescence.ResultsIn the present study, 11.3% of the studied patients had significant visual field changes upon testing. Of those, 6.3% had abnormal fundus autofluorescence. We found a significant statistical relation between hydroxychloroquine retinopathy and the duration and cumulative dose of hydroxychloroquine therapy (p value = 0.003) and decreased best-corrected visual acuity of both eyes (p value = 0.000). There was no relationship between HCQ retinopathy detected by fundus autofluorescence and daily dose of HCQ/kg, age, sex, and SLEDAI score.ConclusionFrequency of SLE patients who had confirmed HCQ-induced retinopathy was 6.3%. Hydroxychloroquine could be safely used in all SLE patients regardless of age, sex, and SLE activity. Routine ophthalmological assessment is recommended for SLE patients who received HCQ especially for those who received HCQ longer than 7 years. Fundus autofluorescence is a modern objective tool which is specific for the early detection of HCQ retinopathy.

Fundus Autofluorescence after Half-Dose Photodynamic Therapy for Chronic Central Serous Chorioretinopathy

Introduction: To evaluate the fundus autofluorescence (FAF) images 1 year after half-dose photodynamic therapy (hdPDT) for chronic central serous chorioretinopathy (CSC). Methods: Forty-six eyes of 46 consecutive patients with chronic CSC underwent hdPDT. Short wavelength-elicited FAF images and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded before and at 1, 3, 6, 9, and 12 months after the hdPDT. The FAF images at 1 month were compared to those at 12 months after the hdPDT. Results: The serous retinal detachment (SRD) was resolved in all eyes. The best-corrected visual acuity (BCVA) improved significantly from 0.13 ± 0.28 logarithm of minimum angle of resolution (logMAR) units before to 0.01 ± 0.17 logMAR units at 12 months after the hdPDT (p = 0.001; paired t test). The mean choroidal thickness decreased significantly from 365.4 ± 103.0 µm to 284.3 ± 92.5 µm at 12 months (p < 0.001). Abnormal FAF images were present within the irradiated area in all the eyes before the hdPDT. In 5 of 46 eyes, identifiable changes of the FAF images were observed 12 months after hdPDT. None of the eyes had the confluent hypo-FAF type during the follow-up period. Univariate analyses showed that the choroidal thickness before hdPDT correlated significantly with hypo-FAF enlargement (p = 0.005). However, multivariate analyses showed that the association was not significant (p = 0.06). Conclusions: The progression of the RPE damages occurred in approximately one-tenth of the eyes that underwent hdPDT for chronic CSC. The long-term effect of progression of hypo-FAF on visual functions remains to be determined.

ULTRA-WIDE FIELD FUNDUS AUTOFLUORESCENCE IMAGING OF EYES WITH STICKLER SYNDROME.

To determine the characteristics of fundus autofluorescence (FAF) images and visual functions in eyes with Stickler syndrome using ultra-widefield FAF images. Forty-six eyes of 26 patients with mutations in the COL2A1 gene underwent ultra-widefield FAF imaging. The eyes were categorized into three types; no signs of abnormal AF, predominantly hyperfluorescent AF (hyper-AF), and predominantly hypofluorescent AF (hypo-AF). Goldmann perimetry was performed on 34 eyes, and line-scan images of the abnormal AF lesions were obtained by swept-source optical coherence tomography in 4 eyes. Abnormal AF lesions were found in 37 eyes of 21 (80.7%) of the 26 patients. Hyper-AF was found in 15 eyes and hypo-AF was found in 22 eyes. The FAF changes corresponded with the funduscopically observed radial paravascular retinal degeneration. The average age at the examination was significantly younger in patients who had eyes with hyper-AF or no abnormal AF than in those with hypo-AF (12.8 vs. 28.4 years; P = 0.009). Abnormal AF-associated visual field defects were found in 5/10 (50%) eyes with hyper-AF and 17/18 (94%) eyes with hypo-AF. Hyper-AF changes tended to appear before retinal changes were detectable by fluorescein angiography. An absence of the ellipsoid zone and the outer nuclear layer and a thinning of the overall retinal thickness were found corresponding to the hypo-AF lesions in the swept source optical coherence tomography images. Abnormal FAF is characteristic of eyes with Stickler syndrome. Age-related alterations of the FAF was associated with visual field defects and disruption of the photoreceptors and retinal pigment epithelial cells.

Association of Clinical and Genetic Heterogeneity With BEST1 Sequence Variations

Detailed phenotypic information on the spectrum of fundus abnormalities and clinical variability of all phenotypes associated with sequence variations in BEST1 is limited. To report a detailed phenotypic and genetic analysis of a patient cohort with sequence variations in BEST1. This retrospective case series took place at the Oxford Eye Hospital in Oxford, UK. Thirty-six patients from a single center with disease-causing sequence variations in BEST1 from 25 different families were analyzed. Data were collected from November 2017 to June 2018, and analysis began April 2018. Results of ocular phenotyping and genetic testing using targeted next-generation sequencing to identify BEST1 sequence variations. Thirty-six patients from 25 families with disease-causing sequence variations in BEST1 were included. Of 36 patients, 20 (55.6%) were female. Three distinct clinical phenotypes were identified: autosomal recessive bestrophinopathy (ARB), best vitelliform macular dystrophy (BVMD), and adult-onset vitelliform macular dystrophy. The ARB phenotype group comprised 18 patients from 9 families with age in years at symptom onset ranging from less than 10 to 40s. All patients showed a common phenotype of fundus autofluorescence abnormalities, and spectral-domain optical coherence tomography features were similar in all patients with schitic and cystoid changes. A phenotype of a beaten metallic retinal appearance extending from the mid periphery to the far periphery was identified in 8 patients. Four patients from 1 family with ARB were previously reported to have autosomal recessive retinitis pigmentosa but were reclassified as having ARB as part of this study. The BVMD phenotype group comprised 16 patients from 14 families with age at symptom onset ranging from less than 10 to 70s. Fundus features were localized to the macula and consistent with the stage of BVMD. In the adult-onset vitelliform macular dystrophy phenotype group, the age in years at symptom onset varied from 50s to 70s in 2 patients from 2 families. Fundus features included small vitelliform lesions. Where available, electro-oculogram results demonstrated a reduced or absent light rise in all patients with ARB and BVMD. Genetic testing identified 22 variants in BEST1. These findings support the notion that ARB, BVMD, and adult-onset vitelliform macular dystrophy are clinically distinct and recognizable phenotypes and suggest that the association of autosomal recessive retinitis pigmentosa with sequence variations in BEST1 should be rereviewed.

Topographic Variations of Choroidal Thickness in Healthy Eyes on Swept-Source Optical Coherence Tomography.

PurposeTo assess topographic variations of choroidal thickness (CT) in the fovea and beyond in healthy eyes.MethodsThis cross-sectional study included healthy subjects ≤ 55 years of age with axial lengths (22–26 mm) and refractive error margins (–4D, +4D) in normal ranges. Images were acquired using swept-source optical coherence tomography angiography (OCT-A). Corneal thickness (CT) maps from 12 × 12-mm radial scans and 9 × 9-mm OCT-A B-scans were analyzed.ResultsThe study included 64 eyes of 33 subjects (mean age, 37 years). Mean CT was >300 µm in all locations except the nasal outer macula. The subfoveal CT was >395 µm in 30% of cases; in 38.7% of cases, >50% of the CT map was thicker than 395 µm. The mean thickest choroidal point was 395.2 µm (range, 164–548 µm), located superior and temporal to the macula in 72.2% of cases and subfoveally in 1.8% of cases. The CT pattern was symmetrical (58%) or asymmetrical (42%) along a horizontal axis correlating with choroidal vein distribution. Half of the asymmetrical patterns were thicker in the inferior quadrants, with an oblique temporal watershed of venous drainage, and the other half were thicker superiorly. The mean vascularity index was ∼75% regardless of the mean CT.ConclusionsOne-third of healthy eyes of patients younger than age 55 had a thick choroid (>395 µm). In these normal eyes, the thickest choroidal point was not subfoveal, CT symmetry above and below the fovea depended on choroidal vein distribution, and choroidal vascularity index was independent from CT. No patients demonstrated fundus autofluorescence abnormalities, and the choriocapillaris remained visible even in thick choroids. These features could be interesting when differentiating normal versus pathological states.

Five-year follow-up of fundus autofluorescence and retinal sensitivity in the fellow eye in exudative age-related macular degeneration in Japan.

To assess the 5-year change in abnormal fundus autofluorescence (FAF) patterns and retinal sensitivity in the fellow eye of Japanese patients with unilateral exudative age-related macular degeneration (AMD). Patients with unilateral exudative AMD who developed abnormal FAF in the fellow eyes were enrolled. FAF imaging and microperimetry were performed at baseline and follow-ups. FAF findings were classified into 8 patterns based on the International Fundus Autofluorescence Classification Group to assess retinal sensitivity. Forty-five points covering the central 12 degrees on microperimetry were superimposed onto the FAF images. Each point was classified depending on the distance from the abnormal FAF. "Close" was defined as the portion within 1 degree from the border of any abnormal FAF, and "Distant" was defined as the portion over 1 degree from the border of abnormal FAF. To investigate the association between the retinal sensitivity and distance from the abnormal FAF, hierarchical linear mixed-effect models were used with the distance, time and time squared from baseline (months), and angle (degrees) as fixed effects. Differences among patients, eyes, and test point locations were considered successively nested random effects. We studied 66 fellow eyes with abnormal FAF. Twenty-seven eyes were followed-up during the 5 years. In the 13 of 27 eyes (48%), the abnormal FAF patterns had changed during the 5 years. We found retinal sensitivity was associated significantly with the distance from the abnormal FAF ("Distant": p<0.001, time2 from baseline: p<0.001, angle: p<0.001). The mean retinal sensitivity of the "Close" tended to deteriorate after the third year and eventually showed the similar sensitivity as the portion within the abnormal FAF. FAF patterns can change about half during the 5 years and the retinal sensitivity near abnormal FAF tends to deteriorate after the third year.