Fundus Autofluorescence Findings Research Articles

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.

Improvements in visual acuity and macular morphology following cessation of anti-estrogen drugs in a patient with anti-estrogen maculopathy resembling macular telangiectasia type 2: a pathogenic hypothesis

BackgroundThe relationship between anti-estrogen drugs and macular telangiectasia type 2 (MacTel-2) remains unknown. Here we report a case with anti-estrogen maculopathy resembling MacTel-2 with improved visual function and macular morphology following cessation of anti-estrogen drugs.Case presentationA 53-year-old woman presented with a 5-month history of central vision loss and anorthopia in both eyes. She had received oral tamoxifen followed by toremifene for 69 months. Funduscopy, fluorescein angiography, and optical coherence tomography (OCT) revealed MacTel-2-like findings OU. Fundus autofluorescence (FAF) showed hyper-autofluorescence at the fovea OU. Visual acuity, macular morphology on OCT, and FAF findings gradually improved after cessation of anti-estrogen drugs.ConclusionsIn the present case, visual acuity, macular morphology, and impairment of the retinal pigment epithelium (RPE) improved following cessation of anti-estrogen drugs, suggesting the relationship between retinal toxicity of anti-estrogen drugs and the development of MacTel-2-like findings. From these results and the previous observations, toxicity of both photoreceptor and RPE cells caused by anti-estrogen drugs may contribute to the development of anti-estrogen maculopathy similar to MacTel-2.

A distinct retinal pigment epithelial cell autofluorescence pattern in choroideremia predicts early involvement of overlying photoreceptors.

Choroideremia is an X-linked retinal disease characterized by early retinal pigment epithelium (RPE) loss and subsequent retinal degeneration. The RPE adopts either a smooth or mottled appearance on fundus autofluorescence (FAF). It is not known how RPE changes predict the health of the overlying ellipsoid zone (EZ). A retrospective review of FAF and optical coherence tomography (OCT) images from 20 patients with choroideremia was performed. The percentage of intact EZ in each smooth and mottled FAF region was determined using one horizontal trans-foveal OCT section. Fourteen out of 20 patients had distinct smooth and mottled areas in both eyes and were included in the sub-analysis. On average, 62.5±10.1% of the EZ in each smooth region of the right eyes was intact compared to 10.0±4.3% in the mottled areas. The same trend was observed in left eyes: 76.5±7.2% of the EZ was intact in the smooth regions versus 9.8±3.9% in the mottled areas (two-way anova, p<0.0001). Thus, the mottled FAF regions were associated with EZ disruption more so than the smooth areas. Retinal pigment epithelium (RPE) changes correlate with the health of the overlying EZ in choroideremia. The smooth FAF region likely represents early stages of the disease, with most of the area containing preserved EZ, whereas the mottled zone indicates more advanced stages and has mostly disrupted EZ. Because of the clear relationship between FAF findings and EZ integrity, FAF imaging can be used to monitor disease progression and identify areas of preserved EZ that could be rescued by gene therapy.

GUCY2D-Associated Leber Congenital Amaurosis: A Retrospective Natural History Study in Preparation for Trials of Novel Therapies

PurposeTo describe the natural history of Leber congenital amaurosis (LCA) associated with GUCY2D variants (GUCY2D-LCA) in a cohort of children and adults, in preparation for trials of novel therapies.DesignRetrospective case series.MethodsParticipants: Patients with GUCY2D-LCA at a single referral center. Procedures: Review of clinical notes, retinal imaging including fundus autofluorescence (FAF) and optical coherence tomography (OCT), electroretinography (ERG), and molecular genetic testing. Main Outcome Measures: Demographic data, symptoms at presentation, visual acuity, evidence of progression, OCT and FAF findings, ERG assessment, and molecular genetics.ResultsTwenty-one subjects with GUCY2D-LCA were included, with a mean follow-up ± standard deviation (SD) of 10 ± 11.85 years. Marked reduction in visual acuity (VA) and nystagmus was documented in all patients within the first 3 years of life. Fifty-seven percent (n = 12) exhibited photophobia and 38% (n = 8) had nyctalopia. VA was worse than hand motion in 71% of the patients (n = 15). Longitudinal assessment of VA showed stability in all patients, except 1 patient who experienced deterioration over a follow-up of 44 years. Hyperopia was reported in 13 of the 17 subjects (71%) with available refraction data. Eighteen subjects had either normal fundus appearance (n = 14) or a blond fundus (n = 3), while only 4 of the eldest subjects had mild retinal pigment epithelium (RPE) atrophy (mean, 49 years; range 40-54 years). OCT data were available for 11 subjects and 4 different grades of ellipsoid zone (EZ) integrity were identified: (1) continuous/intact EZ (n = 6), (2) focally disrupted EZ (n = 2), (3) focally disrupted with RPE changes (n = 2), and (4) diffuse EZ disruption with RPE changes (n = 1). All examined subjects had stable OCT findings over the long follow-up period. Full-field ERGs showed evidence of a severe cone-rod dystrophy in 5 of 6 patients and undetectable ERGs in 1 subject. Novel genotype-phenotype correlations are also reported.ConclusionGUCY2D-LCA is a severe early-onset retinal dystrophy associated with very poor VA from birth. Despite the severely affected photoreceptor function, the relatively preserved photoreceptor structure based on EZ integrity until late in the disease in the majority of subjects suggests a wide therapeutic window for gene therapy trials.

Double-Layer Sign: A New OCT Finding in Active Tubercular Serpiginous-like Choroiditis to Monitor Activity

Purpose To describe a novel spectral-domain (SD) OCT finding of a double-layer sign at the site of activity in tubercular serpiginous-like choroiditis (SLC) and how this sign can be used to assess treatment response in these eyes. Design Retrospective, observational case series. Methods We retrospectively reviewed simultaneous fundus photographs and SD OCT and fundus autofluorescence (FAF) images of eyes affected with tubercular SLC from the acute stage until resolution of lesions using the Heidelberg Spectralis HRA and OCT system (Heidelberg Engineering, Heidelberg, Germany). Main Outcome Measures Occurence of the double layer sign (DLS) during activity; reduction in the double layer sign (DLS) with resolution of choroidal and retinal inflammation; correlation of SD OCT and FAF findings. Results Five eyes of 5 patients were studied in detail. Spectral-domain OCT findings included choroidal elevation and a double-layer sign (separation of hyperreflective retinal pigment epithelium [RPE] from Bruch’s membrane, with the gap between them showing moderate reflectivity) at the site of activity. This correlated with hyperautofluorescence with indistinct borders on FAF imaging. Reduction in the double-layer sign became evident as the lesions began to resolve, and eventually this area was replaced by hyperreflective, irregular, knobbly elevations of the RPE. In eyes with severe inflammation and increased choroidal elevation on OCT, the double-layer sign was very prominent. As the choroidal elevation decreased on OCT, increased reflectance from the choroidal layers was evident. As the lesions resolved, the lesions became predominantly hypoautofluorescent on FAF and loss of RPE, ellipsoid zone, and external limiting membrane on SD OCT scan became evident. Good correlation was found between the resolution of the double-layer sign on SD OCT and FAF findings. Conclusions The double-layer sign on SD OCT may be a useful finding in monitoring the activity in tubercular SLC. The OCT changes can be correlated with FAF imaging in these eyes.

Association of Fundus Autofluorescence Findings and Outer Retinal Lesions on Optical Coherence Tomography With Visual Acuity in Birdshot Chorioretinopathy.

This article investigates the optical coherence tomography (OCT) and fundus autofluorescence imaging findings in birdshot chorioretinopathy (BSCR) and their association with visual acuity (VA). In a retrospective, cross-sectional study, we evaluated OCT images for changes in retinal structure including cystoid macular edema (CME), epiretinal membrane, and outer retinal lesions. We assessed autofluorescence images for hypoautofluorescent and hyperautofluorescent changes and noted the distribution of the lesions. Demographic data and VA at the time of imaging were also collected. Associations between OCT and autofluorescence findings and logarithm of the minimum angle of resolution VA were tested using linear regression. We conducted a chart review of 80 eyes from 40 patients with BSCR. Outer retinal lesions were found on OCT in 28 of 80 eyes (35%) and disruption of the outer segment ellipsoid zone (EZ) occurred in 23 eyes (28.7%). Macular hypoautofluorescent lesions were more common than hyperautofluorescent lesions, present in 58.8% and 13% of eyes, respectively. The presence of outer retinal lesions on OCT was significantly associated with reduced VA (P = .006) as was EZ disruption (P = .003). These associations remained significant after accounting for the presence of macular edema. There was a trend toward association of macular hypoautofluorescent lesions with decreased vision, although it was not statistically significant (P = .17). The association of outer retinal lesions with decreased VA suggests a mechanism of central vision loss that is distinct from CME and may provide an additional objective finding to monitor disease activity in BSCR patients.

A Workshop on Measuring the Progression of Atrophy Secondary to Stargardt Disease in the ProgStar Studies: Findings and Lessons Learned.

The Progression of Atrophy Secondary to Stargardt Disease (ProgStar) studies were designed to measure the progression of Stargardt disease through the use of fundus autofluorescence imaging, optical coherence tomography, and microperimetry. The overarching objectives of the studies were to document the natural course of Stargardt disease and identify the most appropriate clinical outcome measures for clinical trials assessing the efficacy and safety of upcoming treatments for Stargardt disease.A workshop organized by the Foundation Fighting Blindness Clinical Research Institute was held on June 11, 2018, in Baltimore, MD, USA. Invited speakers discussed spectral-domain optical coherence tomography, fundus autofluorescence, and microperimetry methods and findings in the ProgStar prospective study. The workshop concluded with a panel discussion of optimal endpoints for measuring treatment efficacy in Stargardt disease. We summarize the workshop presentations in light of the most current literature on Stargardt disease and discuss potential clinical outcome measures and endpoints for future treatment trials.

Enhanced depth imaging and swept-source optical coherence tomography findings in choroidal osteoma: a case report

The aim of this study was to report the findings from enhanced depth imaging (EDI) and swept-source optical coherence tomography (OCT) in a choroidal osteoma. A case study of a patient with choroidal osteoma is presented and discussed. A 25-year-old woman presented with an asymptomatic peripapillary mass. Fundus examination revealed a yellow–orange, well-defined geographical lesion. B‑scan ultrasonography, corroborated by fundus autofluorescence (FAF) and OCT findings, pointed to the diagnosis of choroidal osteoma. Calcified areas of the tumor were iso-autofluorescent on FAF and hyporeflective on OCT, revealing the morphological patterns of cancellous bone, including a sponge-like pattern and lines indicating lamellae, Haversian canals, and cement lines. Decalcified patches of the tumor were hypofluorescent on FAF and hyperreflective on OCT and showed overlying retinal damage—most prominently depigmentation and retinal pigment epithelium disruptions. A central area of the tumor revealed unusual characteristics; hyperreflectivity on OCT indicating decalcification but isofluorescence on FAF and sharing the same color as the rest of the retina on fundus photography. The area also differed from the other decalcified areas with its cumulus cloud-like appearance. Compared with EDI-OCT, SS-OCT images showed some increased definition of the bony features of the tumor, especially in its deeper layers, as well as a mild reduction of the shadowing caused by overlying retinal vessels. The morphological features of a choroidal osteoma are demonstrated using EDI- and SS-OCT. Calcified and decalcified areas of the tumor were differentiated, as well as another area showing unexpected characteristics. In our case, SS-OCT imaging revealed very similar features to EDI-OCT.

Fundus autofluorescence and retinal sensitivity in fellow eyes of age-related macular degeneration in Japan.

PurposeAbnormal fundus autofluorescence (FAF) potentially precedes onset of late age-related macular degeneration (AMD) in Caucasian patients. Many differences exist between Asian and Caucasian patients regarding AMD types and severity, gender, and genetic backgrounds. We investigated the characteristics of abnormal FAF and retinal sensitivity in the fellow eyes of Japanese patients with unilateral neovascular AMD.MethodsSixty-six patients with unilateral neovascular AMD and abnormal FAF in the fellow eye were enrolled in this multicenter, prospective, observational study. The best-corrected visual acuity, fundus photographs, FAF images, and retinal sensitivity on microperimetry were measured periodically for 12 months. The FAF images were classified into eight patterns based on the International Fundus Autofluorescence Classification Group. The points measured by microperimetry were superimposed onto the FAF images and fundus photographs and classified as “within,” “close,” and “distant,” based on the distance from the abnormal FAF and other findings. The relationship between the location of the baseline abnormal FAF and retinal sensitivity was investigated.ResultsIn Japanese patients, patchy (33.3%) and focally increased (30.3%) patterns predominated in the abnormal FAF. Intermediate-to-large drusen was associated predominantly with hyperfluorescence and hypofluorescence. Neovascular AMD developed within 1 year in six (9.1%) eyes, the mean baseline retinal sensitivity of which was 12.8 ± 4.7 dB, significantly (p<0.002) lower than the other eyes. In 44 of the other 60 eyes, microperimetry was measurable at baseline and month 12 and the mean retinal sensitivity improved significantly from 13.5 ± 4.4 to 13.9 ± 4.8 dB (p<0.001), possibly associated with lifestyle changes (e.g., smoking cessation, antioxidant and zinc supplementation). The mean retinal sensitivities of points within and close to the abnormal FAF were 9.9 and 11.7 dB, respectively, which were significantly lower than the 14.0 dB of the points distant from the abnormal FAF.ConclusionIn Japanese patients, patchy and focally increased patterns predominated in the abnormal FAF. The retinal sensitivity was lower close to/within the abnormal FAF. FAF and microperimetry are useful to assess macular function before development of neovascular AMD or geographic atrophy.

Fundus Autofluorescence Changes in Age-related Maculopathy

Objectives:The aim of this study was to describe the fundus autofluorescence (FAF) findings of age-related maculopathy and risk patterns associated with FAF changes.Materials and Methods:FAF images of 150 eyes with age-related maculopathy were evaluated retrospectively. FAF patterns were classified as normal, minimal change, focal increase, patchy, linear, lace-like, reticular, and speckled pattern. Correlation between patterns and visual acuity, pattern associations at initial visit, and focal atrophy development and pattern alterations during follow-up were evaluated.Results:At initial examination, 33.3% of the eyes showed no FAF pattern. In the other eyes, the most common patterns were reticular, focal increase, and patchy pattern at rates of 18%, 14.7%, and 11.3%, respectively. There was no correlation between pattern and visual acuity at initial visit. Two coexisting patterns were observed in 4.6% eyes, and the most common pattern in these combinations was reticular pattern (85.7%). Pattern alterations were observed in 5.3% of the eyes during follow-up. Half of these alterations involved transformation to reticular pattern or addition of reticular pattern to the initial pattern. In addition, 13.3% of the eyes developed focal atrophy during follow-up. Development of focal atrophy was more common with focal increase and reticular pattern, with rates of 45% and 30%, respectively.Conclusion:Presence of reticular pattern may be a risk factor for change and progression of FAF findings in age-related maculopathy.

En Face Optical Coherence Tomography Imaging of the Photoreceptor Layers in Hydroxychloroquine Retinopathy

To investigate the application of en face optical coherence tomography (OCT) imaging in eyes with hydroxychloroquine (HCQ) retinopathy. Retrospective case series. Setting: Institutional. Sixty-two eyes of 31 Asian patients with HCQ retinopathy. Macular volume scanning using swept-source OCT was performed in 6× 6-mm and 9× 9-mm areas centered on the fovea. Segmentation of the photoreceptor layers was automatically performed between the inner border of the ellipsoid zone and that of the retinal pigment epithelium-Bruch membrane complex to obtain en face OCT images. Findings from the en face images were qualitatively and quantitatively evaluated; they were analyzed and correlated with the fundus autofluorescence and visual field findings. En face OCT findings. All eyes with HCQ retinopathy had a beaten-bronze appearance in the areas with photoreceptor defects, whereas those with intact photoreceptors had areas with smooth surfaces, which were occasionally demarcated by hyporeflective margins, on the en face OCT images. The presence and extent of the retinopathy could be quickly determined using the images. They also provided quantitative information on the progression based on the areas of intact photoreceptors compared over several visits. Furthermore, the area of central intact photoreceptors significantly correlated with the mean deviation, pattern standard deviation, and visual field index of 30-2 visual field examinations (all P < .001). En face OCT may be useful for visualizing the presence and extent of HCQ retinopathy and its progression. The area of central intact photoreceptors measured on en face OCT images showed a significant association with functional visual field defects. This imaging may be a helpful adjunct for screening and follow-up examinations of HCQ retinopathy.

Evaluation of Retromode Imaging for Use in Hydroxychloroquine Retinopathy

To report on the application of retromode imaging using infrared lasers to eyes with hydroxychloroquine (HCQ) retinopathy, and to compare retromode images with those acquired via conventional objective screening imaging modalities-optical coherence tomography (OCT) and fundus autofluorescence (FAF). Diagnostic validity assessment. Setting: Institutional. Sixty-two eyes of 31 patients with systemic lupus erythematosus or rheumatoid arthritis who were treated with HCQ and developed HCQ retinopathy (patient group), 270 eyes of 135 patients with the same diseases who were treated with HCQ but exhibit no retinopathy (HCQ-taking control group), and 162 eyes of 81 normal controls (normal control group). Diagnosis of HCQ retinopathy was performed with screening tests recommended by the American Academy of Ophthalmology, including OCT, FAF, and visual field examination. Retromode imaging, using confocal scanning laser ophthalmoscopy, was performed for the patient group and both control groups. The findings on retromode imaging were correlated with outer retinal changes on OCT B-scan images, then compared with the FAF findings. The sensitivity and specificity of retromode imaging were calculated. Findings of retromode imaging and sensitivity/specificity of the imaging. All patients with HCQ retinopathy showed a parafoveal or pericentral ring-shaped or round area of decreased reflectance with prominent deep choroidal vessels, resulting in 100% sensitivity for the detection of retinopathy. Specificity of the imaging was 73.0% and 76.4% in the HCQ-taking control group and both control groups, respectively. Compared to FAF, retromode imaging enabled the detection of photoreceptor defects with greater sensitivity, particularly in eyes with early retinopathy. However, FAF provided additional information on the status of the retinal pigment epithelium, which could not be discriminated from photoreceptor defects in retromode imaging. Retromode imaging may be useful for detecting HCQ retinopathy. However, its excellent sensitivity but limited specificity is suggestive of a supplementary role in screening HCQ retinopathy, particularly for early detection.

Spectral domain optical coherence tomography and fundus autofluorescence findings in cytomegalovirus retinitis in HIV-infected patients.

To assess the usefulness of spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) findings in cytomegalovirus (CMV) retinitis. Observational case series. Thirteen eyes of 11 human immunodeficiency virus (HIV)-positive patients with CMV retinitis underwent full ophthalmologic examinations, SD-OCT, and 4 eyes of 4 patients underwent FAF. FAF images included short-wavelength autofluorescence (SW-AF) and near-infrared autofluorescence (IR-AF). CMV retinitis was classified into proposed categories of acute, subacute, remission, and recurrent; the acute stage was further subdivided into initial, early, and late stages. In the initial stage, vertical structural disruption of all retinal layers was observed by SD-OCT, and FAF showed hyperautofluorescence on SW-AF and hypoautofluorescence on IR-AF. In the early stage, SD-OCT showed significant retinal thickening; cells and debris from the retinal surface to the vitreous; enlarged vessels with/without thickened vessel walls; and highly complicated serous retinal detachment. In the late to subacute stage, features observed included rhegmatogenous retinal detachment with shrinking posterior hyaloid membrane and waving from the ellipsoid zone to the retinal pigment epithelium. In remission, FAF findings were hypoautofluorescence on SW-AF and hyperautofluorescence on IR-AF. Although the number of examined eyes was limited, SD-OCT and FAF provide new information in various stages of CMV retinitis in patients with HIV infection that is not obtainable by conventional examination and which may be of great benefit when screening for the initial stage of CMV retinitis.

Baseline Predictors of Visual Acuity Outcome in Patients with Wet Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is one of the leading causes of severe vision loss in people over 60 years. Wet AMD (wAMD) causes more severe visual acuity (VA) loss compared with the dry form due to formation of choroidal neovascularization (CNV). Antivascular endothelial growth factor (anti-VEGF) agents such as ranibizumab and aflibercept are now the standard of care treatment for wAMD. Unfortunately, up to a quarter of anti-VEGF-treated wAMD patients might not fully benefit from intravitreal injections and CNV activity may not respond to the treatment and these patients are called anti-VEGF nonresponders. This article aims to discuss the baseline factors associated with VA outcome such as age, initial VA, lesion types, disease duration, optical coherence tomography (OCT) features, fundus autofluorescence findings, and the presence of particular genotype risk alleles in patients with wAMD. Recommendations are provided regarding when to consider discontinuation of therapy because of either success or futility. Understanding the predictive factors associated with VA outcome and treatment frequency response to anti-VEGF therapy may help retina specialists to manage patients' expectations and guide treatment decisions from the beginning of treatment on the basis of “personalized medicine.”

Swept-Source OCT Angiography of Serpiginous Choroiditis

To examine and quantify choriocapillaris lesions in active and quiescent serpiginous choroiditis (SC) using swept-source optical coherence tomography angiography (SS-OCTA) and en-face image analysis. Prospective observational case series. Patients with a clinical diagnosis of SC. A SS-OCTA prototype was used to image active and quiescent serpiginous lesions longitudinally before and after anti-inflammatory treatment. En-face slabs of choriocapillaris flow (CC-slab) or outer nuclear layer structure (ONL-slab) were generated from OCTA and OCT data, respectively. Qualitative and quantitative analyses on lesion boundary and area using a semi-automated MATLAB algorithm. Lesions were also compared to traditional multimodal imaging. Six eyes of three patients were imaged. Choroidal lesions were identified and analyzed in four of six eyes. Lesions with well-defined boundaries were identified in the CC-slab in areas of both active and inactive choroiditis. CC-slab lesion size and shape showed good correlation with lesions identified on indocyanine green angiography. CC-slab lesion area increased with disease activity and decreased with corticosteroid treatment. During active disease, the CC-slab lesion area was larger than both the ONL-slab and fundus autofluorescence lesion areas. Active CC-slab lesions not associated with corresponding abnormal autofluorescence resolved without clinical scarring after treatment. In inactive scars, the areas of retinal and choriocapillaris lesions were similar and did not change over time. En-face analysis of SS-OCTA choriocapillaris flow voids provide a non-invasive method for the detection of lesions in patients with SC. The presence of lesions in the choriocapillaris in the absence of retinal pigment epithelium and outer retinal abnormalities supports the hypothesis that choriocapillaris is the primary site of pathology in SC, and may be a sensitive early sign of disease activity. We propose a simple grading system of SC lesions based on SS-OCTA and fundus autofluorescence findings. SS-OCTA is a promising non-invasive method for monitoring patients with SC.

Clinical and imaging findings of pattern dystrophy subtypes; Diagnostic errors and unnecessary treatment in clinical practice

To evaluate the clinical and multimodal imaging findings of various pattern dystrophy (PD) subtypes and report the initial misdiagnosis rate of PD patients resulting in unnecessary treatment in actual clinical practice. Retrospective, observational study. Forty eyes of 24 patients with PD were included. The distribution of PD subtypes, optical coherence tomography (OCT) and fundus autofluorescence (FAF) findings, initial misdiagnoses, revised diagnoses, duration between misdiagnosis and revised diagnosis, and unnecessary treatments administered were evaluated over this time-period. Twenty-eight eyes (70%) showed adult-onset foveomacular vitelliform dystrophy, 6 eyes (15%) showed butterfly PD (BPD), 4 eyes (10%) showed reticular PD, and 2 eyes (5%) showed PD simulating fundus flavimaculatus and BPD mixed type PD. Most of the patients showed various types of hyperreflective material in the subretinal space on OCT, and hyperautofluorescence on FAF imaging. Eighteen eyes (45%) had a true PD diagnosis initially, whereas 22 (55%) of them were misdiagnosed as age-related macular degeneration, central serous chorioretinopathy, or non-specific RPE change. The mean duration between the initial and revised diagnosis was 18.7±16.8 months. In addition, 5 eyes in the misdiagnosed group underwent intravitreal anti-vascular endothelial growth factor treatment during this period. Pattern dystrophies are a heterogeneous group of macular disorders which may mimic several macular diseases. By knowing the multimodal imaging findings, especially the distinctive FAF findings of the PDs, we may easily diagnose the disease and save our patients from unnecessary treatments.

Fundus autofluorescence imaging in hereditary retinal diseases.

Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used in clinical practice to non-invasively map changes at the level of the retinal pigment epithelium (RPE)/photoreceptor complex and alterations of macular pigment distribution. This imaging method is based on the visualization of intrinsic fluorophores and may be easily and rapidly used in routine patient care. Excessive accumulation of lipofuscin granules in the lysosomal compartment of RPE cells represents a common downstream pathogenic pathway in various hereditary and complex retinal diseases. The clinical applications of FAF continue to expand. It is now an essential tool for evaluating macular dystrophies and various hereditary retinal disorders. Fundus autofluorescence (FAF) may detect abnormalities beyond those detected on funduscopic examination, fluorescein angiography (FA) or optical coherence tomography (OCT). Fundus autofluorescence (FAF) imaging is particularly helpful for differential diagnosis, detection and extent delineation of involved retinal areas, genotype-phenotype correlations and monitoring of changes overtime. Given its ease of use, non-invasive nature and value in characterizing retinal disease, FAF enjoys increasing clinical relevance. This review summarizes basic principles and FAF findings in various hereditary retinal diseases.

Fundus Autofluorescence Findings in Eyes With Birdshot Chorioretinitis.

The purpose of this study was to describe fundus autofluorescence (FAF) findings in eyes with birdshot chorioretinitis (BSCR) and to compare findings to demographic, medical, and clinical characteristics. In this multicenter, prospective, cross-sectional study, 172 eyes (86 patients) with BSCR were investigated. Participants underwent a standardized evaluation including collection of demographic data, ophthalmic and treatment history, and ophthalmologic examination. Using a standardized protocol, hypo- and hyperautofluorescence in macular and extramacular regions and specific patterns of abnormal FAF could be scored for 167 eyes. Images were scored by two independent, masked graders. Measures of visual function included best-corrected visual acuity (BCVA), contrast sensitivity (CS), color vision, and Humphrey visual field mean deviation (HVF-MD). Any abnormal FAF finding was observed in 132 eyes (79.0%); macular abnormalities were observed in 84 eyes (49.1%). The most common findings were peripapillary confluent hypoautofluorescence (122 eyes [73.1%]); extramacular granular hypoautofluorescence (100 eyes [59.9%]); and macular granular hypoautofluorescence (67 eyes [40.1%]). Confluent hypoautofluorescence was related to longer median disease duration (8.7 years) than granular hypoautofluorescence (7.9 years) or hyperautofluorescence (5.6 years). Macular confluent hypoautofluorescence was associated with BCVA ≤20/25 (odds ratio [OR] = 7.83, P = 0.007), BCVA ≤20/50 (OR = 4.94, P = 0.002), and abnormal CS (OR = 4.56, P = 0.009). Presence of macular or extramacular hypoautofluorescence was related to HVF-MD ≤-3 dB (OR = 2.43, P = 0.01 and OR = 2.89, P = 0.003, respectively). In this large cohort, various FAF abnormalities were found, indicating that disorders of the retinal pigment epithelium are features of BSCR. Abnormal FAF is a marker of visual dysfunction in the disease.

Ultra-widefield fundus autofluorescence in age-related macular degeneration.

BackgroundEstablish accuracy and reproducibility of subjective grading in ultra-widefield fundus autofluorescence (FAF) imaging in patients with age-related macular degeneration (AMD), and determine if an association exists between peripheral FAF abnormalities and AMD.MethodsThis was a prospective, single-blinded case-control study. Patients were consecutively recruited for the study. Patients were excluded if there was a history of prior or active ocular pathology other than AMD or image quality was insufficient for analysis as determined by two independent graders. Control patients were those without any evidence of AMD or other ophthalmic disease apart from cataract. Using the Optos 200Tx (Optos, Marlborough, MA, USA), a ResMax central macula and an ultra-widefield peripheral retina image was taken for each eye in both normal color and short wavelength FAF. Ultra-widefield photographs were modified to mask the macula. Each ResMax and ultra-widefield image was independently graded by two blinded investigators.ResultsThere were 28 AMD patients and 11 controls. There was a significant difference in the average age between AMD patients and control groups (80 versus 64, respectively P<0.001). There was moderate, statistically significant agreement between observers regarding image interpretation (78.4%, K = 0.524, P<0.001), and 69.0% (K = 0.49, P<0.001) agreement between graders for FAF abnormality patterns. Patients with AMD were at greater risk for peripheral FAF abnormalities (OR: 3.43, P = 0.019) and patients with FAF abnormalities on central macular ResMax images were at greater risk of peripheral FAF findings (OR: 5.19, P = 0.017).ConclusionSubjective interpretation of FAF images has moderate reproducibility and validity in assessment of peripheral FAF abnormalities. Peripheral FAF abnormalities are seen in both AMD and control patients. Those with AMD, poor visual acuity, and macular FAF abnormalities are at greater risk.

Whole-Exome Sequencing Identifies Biallelic IDH3A Variants as a Cause of Retinitis Pigmentosa Accompanied by Pseudocoloboma

To identify the genetic cause of and describe the phenotype in 4 families with autosomal recessive retinitis pigmentosa (arRP) that can be associated with pseudocoloboma. Case series. Seven patients from 4 unrelated families with arRP, among whom 3 patients had bilateral early-onset macular pseudocoloboma. We performed homozygosity mapping and whole-exome sequencing in 5 probands and 2 unaffected family members from 4 unrelated families. Subsequently, Sanger sequencing and segregation analysis were performed in additional family members. We reviewed the medical history of individuals carrying IDH3A variants and performed additional ophthalmic examinations, including full-field electroretinography, fundus photography, fundus autofluorescence imaging, and optical coherence tomography. IDH3A variants, age at diagnosis, visual acuity, fundus appearance, visual field, and full-field electroretinography, fundus autofluorescence, and optical coherence tomography findings. We identified 7 different variants in IDH3A in 4 unrelated families, that is, 5 missense, 1 nonsense, and 1 frameshift variant. All participants showed symptoms early in life, ranging from night blindness to decreased visual acuity, and were diagnosed between the ages of 1 and 11 years. Four participants with biallelic IDH3A variants displayed a typical arRP phenotype and 3 participants were diagnosed with arRP and pseudocoloboma of the macula. IDH3A variants were identified as a novel cause of typical arRP in some individuals associated with macular pseudocoloboma. We observed both phenotypes in 2 siblings carrying the same compound heterozygous variants, which could be explained by variable disease expression and warrants caution when making assertions about genotype-phenotype correlations.