Blue-light Fundus Autofluorescence Research Articles

Correlation Between Blue Fundus Autofluorescence and SD-OCT Measurements of Geographic Atrophy in Dry Age-Related Macular Degeneration

To compare fundus autofluorescence (FAF) and spectral domain optical coherence tomography (OCT) measurements of geographic atrophy (GA) area and to analyze lesion area changes measured by spectral domain OCT in GATHER1. An assessment reliability analysis using prospective, randomized, double-masked phase 2/3 clinical trial data. GATHER1 examined the efficacy and safety of avacincaptad pegol (ACP) for GA treatment. A post hoc analysis was performed to identify correlations between FAF- and OCT-based measurements of GA. GA area was measured on blue-light FAF images using semiautomatic segmentation software with support from OCT and near-infrared imaging. Machine-learning enhanced, multilayer segmentation of OCT scans were reviewed by human readers, and segmentation errors were corrected as needed. GA area was defined as total RPE loss on cross-sectional B scans. Time points included Months 0, 6, 12, and 18. Additionally, OCT-based GA-area changes between ACP and sham were analyzed. There was a strong correlation (r = 0.93) between FAF and OCT GA area measurements that persisted through 18 months. Mean (SD) differences between OCT and FAF GA measurements were negligible: 0.11 mm2 (1.42) at Month 0, 0.03 mm2 (1.62) at Month 6, -0.17 mm2 (1.81) at Month 12, and -0.07 mm2 (1.78) at Month 18. OCT assessments of GA growth revealed a 30% and 27% reduction at Months 12 and 18, respectively, between ACP and sham, replicating FAF measurements from GATHER1. The strong correlation between blue FAF and OCT measurements of GA area supports OCT as a reliable method to measure GA lesion area in clinical trials.

Comparison of Blue-Light Autofluorescence and Ultrawidefield Green-Light Autofluorescence for Assessing Geographic Atrophy

The goal of this study was to evaluate and compare the intermodality and interreader agreement of manual and semiautomated geographic atrophy (GA) area measurements in eyes with GA due to age-related macular degeneration (AMD) using conventional blue-light fundus autofluorescence (FAF) and ultrawidefield (UWF) green-light FAF systems. Prospective Cohort Study. Seventy-two eyes of 50 patients with a diagnosis of advanced nonneovascular AMD with GA. Fundus autofluorescence images of eyes with GA were obtained during a single visit using both the Spectralis HRA+ OCT2 device and the Optos California device. The area of the GA lesion(s) was segmented and quantified (mm2) with a fully manual approach where the lesions were outlined using Optos Advance and Heidelberg Eye Explorer (HEYEX) software. In addition, for the Heidelberg blue FAF images, GA lesions were also measured using the instrument's semiautomated software (Region Finder 2.6.4). For comparison between modalities/grading method, the mean values of the 2 graders were used. Intraclass correlation coefficients were computed to judge the agreement between graders. Seventy-two eyes of 50 patients were included in this study. There was nearly perfect agreement between graders for the measurement of GA area for all 3 modalities (intraclass correlation coefficient: 0.996 for manual Optos Advance, 0.996 for manual Heidelberg HEYEX, and 0.995 for Heidelberg Region Finder). The measurement of GA area was strongly correlated between modalities, with Spearman correlation coefficients of 0.985 (P < 0.001) between manual Heidelberg and manual Optos, 0.991 (P < 0.001) for Region Finder versus manual Heidelberg, and 0.985 (P < 0.001) for Region Finder versus manual Optos. The absolute mean area differences between the Heidelberg manual versus Region Finder, manual Optos versus Region Finder, and manual Optos versus manual Heidelberg were 1.61 mm2 (P < 0.001), 0.90 mm2 (P < 0.006), and 0.71 mm2 (P<0.001), respectively. We observed excellent interreader agreement for measurement of GA using either 30-degree blue-light FAF or UWF green-light FAF, establishing the reliability of UWF imaging for macular GA assessment. Although the absolute measurements between devices were strongly correlated, they differed significantly, highlighting the importance of using the same device for a given patient for the duration of a study. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Changes in Optical Coherence Tomography and Fundus Autofluorescence Findings in Acute Zonal Occult Outer Retinopathy

We report a case of peripapillary acute zonal occult outer retinopathy (AZOOR) in a 43-year-old woman. Fundus photographs showed no specific abnormal findings, while blue-light fundus autofluorescence (FAF) imaging revealed well-defined hyperfluorescent areas in the peripapillary region, excluding the macula. The ellipsoid zone (EZ) was absent on optical coherence tomography (OCT) images of this area. Visual field testing with Goldmann perimetry showed blind spot enlargement and multifocal electroretinogram showed corresponding amplitude reductions. Three months after the initial visit, the EZ had reappeared and both FAF and visual field had improved. FAF together with OCT may be useful in the evaluation and monitoring of AZOOR.

Gradeability and Reproducibility of Geographic Atrophy Measurement in GATHER-1, a Phase II/III Randomized Interventional Trial

To validate GATHER-1 inclusion criteria and the study's primary anatomic end point by assessing the reproducibility of geographic atrophy (GA) measurements and factors that affect reproducibility. Post hoc analysis of phase II/III clinical trial. All 286 participants included in the GATHER-1 study. For each subject, blue-light fundus autofluorescence (FAF), color fundus photographs, fluorescein angiograms, and OCT scans were obtained on the study eye and fellow eye. Geographic atrophy area and other lesion characteristics were independently graded by 2 experienced primary readers. If the 2 readers differed on gradeability, GA area (> 10%) or other lesion characteristics, the image was graded by an arbitrator whose measurement or characterization was the final grade. The main outcome measures were gradeability and reproducibility of FAF imaging data. Imaging data included lesion area, confluence of GA with peripapillary atrophy (PPA), whether GA involved the foveal centerpoint, and type of hyperautofluorescence pattern. A total of 2004 images (1002 visits, 286 participants) were analyzed. Gradeability (90.5%) and interreader gradeability concordance (90.2%) were high across all visits. Study eye images were more gradable compared with fellow-eye images. A greater proportion of smaller lesions required arbitration, but interreader reproducibility was consistently high for all images. There was no difference in gradeability, gradeability concordance, or lesion-area concordance for images with PPA-confluent GA compared with those with nonconfluent PPA. Foveal centerpoint-involving lesions had lower gradeability and lesion-area concordance. Images with diffuse patterns of hyperautofluorescence had better gradeability and gradeability concordance than those with nondiffuse patterns but had no difference in lesion-area or lesion-area concordance. There is high gradeability and excellent reproducibility measures across all images. These data support the validity of conclusions from GATHER-1 and the chosen inclusion criteria and end point. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Blue-Light Fundus Autofluorescence (BAF), an Essential Modality for the Evaluation of Inflammatory Diseases of the Photoreceptors: An Imaging Narrative.

Our purpose is to describe blue-light fundus autofluorescence (BAF) features of inflammatory diseases of the outer retina characterised by photoreceptor damage. BAF from patients diagnosed with secondary and primary inflammatory photoreceptor damage were retrospectively analyzed and compared to other imaging modalities including fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral domain optical coherence tomography (SD-OCT). Multiple evanescent white dot syndrome (MEWDS), idiopathic multifocal choroiditis (MFC), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous choroiditis (SC), and acute syphilitic posterior placoid chorioretinitis (ASPPC), all cases corresponding to secondary photoreceptor diseases caused by inflammatory choriocapillaris nonperfusion, were included and compared to primary photoreceptor disease entities, including acute zonal occult outer retinopathy (AZOOR) and cancer-associated retinopathy (CAR). Both groups showed increased BAFs of variable intensity. In severe cases of APMPPE and ASPPC, BAF also showed hypoautofluorescent areas. In group 1 (secondary diseases) BAF hyperautofluorescent areas were associated with colocalized ICGA hypofluorescent areas, indicating choriocapillaris nonperfusion; whereas in group 2 (primary diseases), no ICGA signs were detected. The associated colocalized areas of hypofluorescence on ICGA in the first group, which were absent in the second group, were crucial to allow the differentiation between primary (photoreceptoritis) and secondary (choriocapillaritis) photoreceptor diseases. BAF patterns in inflammatory diseases of the outer retina can give relevant information on the photoreceptor and RPE involvement, with ICGA being crucial to detect concurring choriocapillaris damage and differentiating the two pathologies.

Review on imaging methods in non-infectious posterior uveitis, principles, relevance, and practical clinical applications to disease entities

The work-up and diagnosis of posterior uveitis rely heavily on multiple imaging methods that have become available beyond the mere photographic imaging and fluorescein angiography (FA) used to image uveitis in the past. Global assessment and precise follow-up of posterior uveitis were achieved with the development of indocyanine green angiography (ICGA) since the mid-1990ties that, together with FA, made it possible to perform dual FA and ICGA giving information on both the retina and the choroidal compartment. Further non-invasive imaging methods were developed subsequently that contributed to additional valuable information completing the dual FA/ICGA basic appraisal of uveitis, including (1) optical coherence tomography (OCT) giving a quasi-histological morphology of retinal structures of the posterior pole, (2) enhanced-depth imaging OCT (EDI-OCT) allowing to image the choroidal compartment and (3) blue light fundus autofluorescence (BAF) showing the integrity or damage of the retinal pigment epithelium, the photoreceptors and the outer retina. OCT-angiography (OCT-A) became available more recently and presented the advantage to image the retinal and choroidal circulations without needing dye injections, necessary for dual FA/ICGA. This review article will illustrate the principles, relevance and practical applications of these different imaging methods used in uveitis by examining the main categories of non-infectious posterior uveitis entities including (1) retinal inflammatory disorders, inflammatory diseases of the outer retina and of the choriocapillaris (choriocapillaritis) and stromal choroiditis.

Optical Coherence Tomography Angiography (OCT-A) in Uveitis: A Literature Review and a Reassessment of Its Real Role.

The global and precise follow-up of uveitis has become possible with the availability of dual fluorescein (FA) and indocyanine green angiography (ICGA) since the mid-1990s. Progressively, additional non-invasive imaging methods have emerged, bringing value-added precision to the imaging appraisal of uveitis, including, among others, optical coherence tomography (OCT), enhanced-depth imaging OCT (EDI-OCT) and blue light fundus autofluorescence (BAF). More recently, another complementary imaging method, OCT-angiography (OCT-A), further allowed retinal and choroidal circulation to be imaged without the need for dye injection. The purpose of this review was aimed at examining the evidence in published reports indicating whether OCT-A could possibly replace dye angiographic methods, as well as the real practical impact of OCT-A. A literature search in the PubMed database was performed using the terms OCT-angiography and uveitis, OCTA and uveitis and OCT-A and uveitis. Case reports were excluded. Articles were classified into technical reports, research reports and reviews. Articles in the two latter categories were analyzed in a more detailed, individual fashion. Special attention was paid to whether there were arguments in favor of an exclusive rather than complementary use of OCT-A. Furthermore, a synthesis of the main practical applications of OCT-A in the management of uveitis was attempted. Between 2016 (the year of the first articles) and 2022, 144 articles containing the search terms were identified. After excluding case report articles, 114 articles were retained: 4 in 2016, 17 in 2017, 14 in 2018, 21 in 2019, 14 in 2020, 18 in 2021 and 26 in 2022. Seven articles contained technical information or consensus-based terminology. Ninety-two articles could be considered as clinical research articles. Of those, only two hinted in their conclusions that OCT-A could hypothetically replace dye methods. The terms mostly used to qualify the contribution of the articles in this group were "complementary to dye methods", "adjunct", "supplementing" and other similar terms. Fifteen articles were reviews, none of which hinted that OCT-A could replace dye methods. The situations where OCT-A represented a significant practical contribution to the practical appraisal of uveitis were identified. To date, no evidence was found in the literature that OCT-A can replace the classic dye methods; however, it can complement them. Promoting the possibility that non-invasive OCT-A can substitute the invasive dye methods is deleterious, giving the elusive impression that dye methods are no longer inevitable for evaluating uveitis patients. Nevertheless, OCT-A is a precious tool in uveitis research.

Retro-mode imaging of gravitational subretinal fluid associated with optic disc pit maculopathy with extensive retinal schisis in a young myopic patient

A 32-year-old female with high myopia and optic disc pit maculopathy associated with schisis was imaged on the Mirante confocal scanning laser ophthalmoscope (Nidek Co, Ltd, Gamagori, Japan). Scanning laser ophthalmoscope colour fundus photography (A) shows a hypopigmented area corresponding with the schisis (green arrows), whereas the blue-light fundus autofluorescence (B) highlights an oval hyperautofluorescent area consistent with the subretinal fluid (SRF; white arrow), which is a useful landmark to monitor the extension and localization of the fluid during the course of follow-up. Retro-mode illumination (C) demonstrates enhanced visualization of the margin of the SRF (white arrow). The myopic schisis is highlighted on retro-mode illumination (green arrows) as fine radiating lines. Optical coherence tomography demonstrates the schisis associated with subretinal fluid (D). Panel E illustrates more subtle, smaller areas of schisis adjacent to the SRF.

Double Concentric Hyperautofluorescent Ring in EYS-Associated Retinitis Pigmentosa.

A 37-year-old Caucasian female with consanguineous parents and a brother with nonsyndromic retinitis pigmentosa (nsRP) presented with longstanding nyctalopia. The best-corrected visual acuity was 20/20 in both eyes. Anterior segment examination and fundoscopy were unremarkable. Blue light fundus autofluorescence (FAF) revealed a bilateral and symmetrical double concentric hyperautofluorescent ring (Fig. 1). On spectral domain optical coherence tomography, the retinal structure was preserved inside the inner ring, whereas outer retinal atrophy was observed outside its limits. Genetic testing identified the c.5928-2A>G p.? pathogenic variant in homozygosity in EYS gene.FIGURE 1: Double concentric hyperautofluorescent ring in EYS-associated retinitis pigmentosa. Right (A) and left (B) FAF highlights 2 hyperautofluorescent rings, an inner perifoveal ring and an outer ring, located along the vascular arcades and demarcating a diffuse hyperautofluorescent annular surface area. FAF indicates fundus autofluorescence.Whereas a perifoveal/perimacular ring of hyperautofluores-cence is a common FAF finding across several RP genotypes,1 the presence of a double concentric hyperautofluorescent ring was deemed pathognomonic of NR2E3-associated autosomal-dominant RP.2 We describe for the first time the occurrence of this peculiar FAF phenotype in EYS-associated nsRP, highlighting that FAF alone does not seem to be a reliable method of distinguishing between RP genotypes.

BENIGN FOVEAL DEPIGMENTATION: A MULTIMODAL IMAGING INVESTIGATION.

To describe the multimodal imaging characteristics of benign foveal depigmentation. The study was designed as prospective observational case series. Patients with benign foveal depigmentation were prospectively investigated by means of multimodal imaging, including blue-light and near-infrared fundus autofluorescence, optical coherence tomography (OCT), OCT angiography, color testing, microperimetry, and electrophysiology. The main outcome measures were vessel density and retinal pigment epithelium (RPE)/photoreceptor complex OCT reflectivity. Overall, 4 patients were identified, with bilateral and unilateral involvement in 1 case and 3 cases, respectively. Fundus autofluorescence provided variable results, showing more impairment on near-infrared fundus autofluorescence. Structural OCT revealed slight attenuation of the outer retinal bands in the area affected by benign foveal depigmentation, associated with choroidal hypertransmission, whereas enface OCT better delineated the attenuation of the reflectivity signal. The mean reflectivity intensity of RPE/photoreceptor complex was statistically significantly reduced in patients with respect to control subjects in the benign foveal depigmentation area. Optical coherence tomography angiography, color testing, microperimetry, electrooculogram, and electroretinogram findings were normal. Benign foveal depigmentation may represent a focal RPE disease. The limited alterations within the RPE band, as visualized on enface OCT and confirmed on near-infrared fundus autofluorescence, suggest an impairment in melanin production or distribution within the RPE cells.

Mystery of changing choroidal thickness.

Mystery of changing choroidal thickness.

Diagnosis, Mechanisms, and Differentiation of Inflammatory Diseases of the Outer Retina: Photoreceptoritis versus Choriocapillaritis; A Multimodal Imaging Perspective

Background and aim: Inflammatory diseases that affect the outer retina do so by different mechanisms. Some of them result from the direct, primary involvement of the outer retina (primary photoreceptoritis) such as acute zonal outer occult retinopathy (AZOOR). Others affect the photoreceptors secondarily due to the inflammatory involvement of the choriocapillaris. This results in choriocapillaris non-perfusion that damages the photoreceptors due to the ensuing ischaemia, a mechanism characterising primary inflammatory choriocapillaropathies (PICCPs) such as multiple evanescent white dot syndrome (MEWDS), idiopathic multifocal choroiditis (MFC), and others. Thanks to multimodal imaging (MMI), it is now possible to differentiate between these two mechanisms of outer retinal damage. The aim of this study is to determine the MMI characteristics that allow us to differentiate primary photoreceptoritis, including AZOOR, from PICCPs such as MEWDS and MFC. Methods: A series of eight PICCPs cases (five typical MEWDS and three typical active MFC cases) and four typical primary photoreceptoritis/AZOOR cases (five eyes) that had undergone complete MMI investigation, including fundus photography (FP), blue light fundus autofluorescence (BL-FAF), spectral domain optical coherence tomography (SD-OCT), OCT angiography (OCT-A, when available), fluorescein angiography (FA), and indocyanine green angiography (ICGA) were analysed, pointing out the differences that allow us to distinguish primary photoreceptoritis from PICCPs. Results: All primary photoreceptoritis/AZOOR cases showed (1) faint fundus pallor around the fovea, (2) BL-FAF hyperautofluorescence, (3) loss of photoreceptor outer segments (PROS) on SD-OCT, (4) absence of choriocapillary drop-out on OCT-A, (5) normal FA or faint FA hyperfluorescence, and (6) conserved ICGA fluorescence/no hypofluorescent areas; (1), (2), (3), and (5) indicated loss of photoreceptor outer segments, and (4) and (6) indicated conserved choriocapillaris circulation. For PICCPs, (a) fundus showed discreet white dots or none (in MEWDS) and punched-out scars in MFC, (b) BL-FAF hyperautofluorescence, (c) loss of PROS on SD-OCT, (d) FA faint hyperfluorescence in MEWDS, also minimal in active MFC lesions (e) in all cases ICGA hypofluorescent areas; (b) and (c) indicating loss of PROS, and (e) indicating choriocapillaris non-perfusion in all cases. The OCT-A did not show consistent findings with faint or no capillary drop-out in MEWDS and MFC. Conclusions: MMI combining the SD-OCT and BL-FAF clearly showed loss of PROS in both groups, while the ICGA determined whether this was due to choriocapillaris non-perfusion in PICCPs or whether the choriocapillaris was intact in case of primary photoreceptoritis. The FA and OCT-A were found to be less useful and/or less sensitive for the appraisal of both these entities.

Optical coherence tomography findings in patients with transfusion-dependent β-thalassemia

BackgroundStructural ophthalmologic findings have been reported in patients with β-thalassemia due to chronic anemia, iron overload, and iron chelation therapy toxicity in few previous studies. We aimed to investigate structural ocular findings and their relationship with hematological parameters in patients with transfusion-dependent β-thalassemia (TDT).MethodsIn this cross-sectional study, from January 2018 to January 2019, 39 patients with TDT over the age of 18 participated. Multicolor fundus imaging, optical coherence tomography (OCT), and blue light fundus autofluorescence imaging were performed for all patients and 27 age- and sex-matched controls.ResultsThe mean age of patients was 28.6 ± 6.2 years. The central macular thickness and macular thicknesses in all quadrants were significantly thinner in patients than controls (P<0.05). None of the retinal nerve fiber layer (RNFL) measurements were significantly different between TDT patients and controls. There was a significantly negative correlation between hemoglobin with central macula thickness (r=-0.439, P=0.005). All measurements of macular subfield thickness were insignificantly thinner in patients with diabetes mellitus (DM) compared to the non-DM subgroup.ConclusionsMacular thickness was significantly thinner in central macula and entire quadrants in TDT patients compared to healthy individuals; however, all RNFL measurement thicknesses were comparable between the two groups. Close monitoring of TDT patients by periodic ophthalmologic examinations with more focus on diabetic patients, patients with severe anemia and iron overload should be warranted.

Blue-light fundus autofluorescence imaging of pigment epithelial detachments

BackgroundPigment epithelial detachments (PEDs) occur in association with various chorioretinal diseases. With respect to the broad clinical spectrum of PEDs we describe fundus autofluorescence (FAF) characteristics of PEDs.MethodsNinety-three eyes of 66 patients (mean age 71.9 ± 11.1) with uni- or bilateral PED ( ≥ 350 µm) were included in a retrospective cross-sectional study. PEDs were secondary to age-related macular degeneration (n = 79), central serous chorioretinopathy (n = 7), polypoidal choroidal vasculopathy (n = 2), pattern dystrophy (n = 3) or idiopathic PED (n = 2). FAF images were recorded using confocal scanning laser ophthalmoscopy (488 nm excitation wavelength, detection of emission >500 nm). Diagnosis of PED was confirmed using spectral-domain optical coherence tomography. A qualitative FAF grading system was established, and grading was performed by two independent readers.ResultsPEDs showed highly variable characteristics on FAF imaging. FAF within the area of PED was found to be irregular/granular (n = 59, 63.4%), increased (n = 28, 30.1%), decreased (n = 3, 3.2 %), or normal (n = 3, 3.2%). Accompanying FAF changes included condensation of macular pigment (n = 67, 72.0%), focally increased FAF at the PED apex (n = 14, 15.1%) or elsewhere (n = 52, 55.9%), focally decreased FAF (n = 23, 24.7%), a cartwheel-like pattern (n = 10, 10.8%), a doughnut sign (n = 6, 6.5%), and a halo of decreased FAF encircling the PED (completely n = 20, 21.5% or incompletely n = 20, 21.5%).ConclusionsPEDs show a variety of abnormal patterns on FAF imaging. These changes in FAF signals may be secondary to morphological and metabolic alterations within corresponding retinal layers and do not necessarily correspond with the underlying PED subtype or a specific pathology.

Mid-Phase Hyperfluorescent Plaques Seen on Indocyanine Green Angiography in Patients with Central Serous Chorioretinopathy.

(1) Indocyanine green angiography (ICG-A) shows the presence of mid-phase hyperfluorescent area in central serous chorioretinopathy (CSCR). However, their exact meaning remains uncertain. (2) The clinical and multimodal imaging findings of 100 patients (133 eyes) with CSCR, including the enhanced-depth-imaging OCT (EDI-OCT), blue-light fundus autofluorescence (BAF), fluorescein and indocyanine green angiography (FA and ICG-A) findings were reviewed. Mid-phase hyperfluorescent plaques (MPHP) were defined as fairly well circumscribed hyperfluorescent regions during the midphase of the ICG-A. The association between MPHP and other clinical/imaging parameters was assessed using a multiple logistic regression analysis. (3) MPHP were detected in 59.4% of eyes with CSCR. The chronic form of the disease, the presence of irregular pigment epithelium detachments (PED) and the retinal pigment epithelium (RPE) changes seen on FA were associated with the presence of MPHP in the multivariate analysis (p = 0.015; p = 0.018 and p = 0.002; respectively). OCT showed RPE bulges or PED in 98.7% of areas with MPHP and BAF showed changes in 57.3% of areas with MPHP. (4) MPHP were associated with a chronic form of CSCR and colocated with PED or RPE bulges. MPHP should be recognized as a sign of early RPE dysfunction before it is detected with BAF.

Retro mode illumination for detecting and quantifying the area of geographic atrophy in non-neovascular age-related macular degeneration.

To evaluate the ability of retro mode illumination imaging for quantifying atrophy compared to confocal color fundus photography (c-CFP), green light fundus autofluorescence (G-FAF), blue light fundus autofluorescence (B-FAF) using the scanning laser ophthalmoscope (SLO) Mirante device by Nidek (Nidek Co., Ltd, Gamogori, Japan). Eyes with clinical evidence of geographic atrophy (GA) associated with non-neovascular age-related macular degeneration, evaluated at the Doheny Eye Centers-UCLA and Hospital Sacco Milan, were included in this prospective, cross-sectional study. All eyes were imaged with multiple retinal imaging modalities using the SLO Nidek Mirante device: c-CFP, G-FAF, B-FAF, retro mode illumination deviated-right (RMDR), and deviated-left (RMDL). Masked graders measured the GA lesion on each modality and inter-modality and inter-grader repeatability were assessed. The mean (SD) area of GA measured 9.76 (3.82) mm2, 9.75 (3.91) mm2, 9.76 (3.92) mm2, 9.82 (3.87) mm2, and 9.81 (3.86) mm2 using c-CFP, G-FAF, B-FAF, RMDR, and RMDL, respectively (p = 0.2). Inter-modality correlation was high (Pearson's r > 0.9 and p < 0.0001). Agreement between graders was excellent for all modalities. Retro mode imaging demonstrated good agreement for measuring GA compared to other imaging modalities, with a high level of repeatability. Given that retro mode imaging uses infrared light and is comfortable, it may prove to be a useful tool for the assessment of GA in the clinic.

Multimodal imaging of optic disc melanocytoma.

To describe the findings of four patients (four eyes) with optic disc melanocytoma (ODM), using multimodal imaging. Retrospective case series. On ocular ultrasonography ODMs appeared as hyperechogenic lesions with moderate-to-high internal reflectivity. On blue-light fundus autofluorescence, ODMs showed total hypoautofluorescence, while, on infrared reflectance images appeared as bright and well-marginated lesions. MultiColor composite images showed reddish-brown lesions with well-defined margins. Swept-source optical coherence tomography revealed elevated lesions covering the optic disc with an irregular hyperreflective surface, dishomogeneous internal structure with hyperreflective dots, and posterior shadowing. In all cases optical coherence tomography angiography detected intratumoral blood vessels which were not detectable with fluorescein angiography. Multimodal imaging in ODM might be useful both at presentation, increasing the diagnostic accuracy, and at follow-up, providing helpful details, that can help to rule out the possibility of malignant transformation and other ocular complications.

Multimodal Imaging of Fundus Flecks and Macular Atrophy in Stargardt Disease

We imaged a 55-year-old man with Stargardt disease (ABCA4 positive) using the Mirante confocal scanning laser ophthalmoscope (SLO) by Nidek (Nidek Co, Ltd). The SLO color (red, green, and blue) fundus photograph (Fig A) shows the classic appearance of “beaten-bronze” subfoveal macular atrophy with surrounding flecks which appear to radiate from the border. Retro-mode illumination (Fig B) provides a level of 3-dimensionality that better illustrates the atrophy and flecks compared with the blue-light fundus autofluorescence (488 nm) and true color images obtained with the same device (Fig C).

Progression of Atrophy and Visual Outcomes in Extensive Macular Atrophy with Pseudodrusen-like Appearance.

PurposeTo report visual outcomes and rate of retinal pigment epithelium (RPE) atrophy progression in patients with extensive macular atrophy with pseudodrusen-like appearance (EMAP).DesignRetrospective, observational study.ParticipantsPatients with EMAP and symptom onset before 55 years of age, at least 12 months of follow-up using Spectralis blue-light fundus autofluorescence (BAF) and OCT and with no other ocular or systemic conditions.MethodsBest-corrected visual acuity (BCVA), BAF, and OCT images were reviewed at baseline and at each annual visit until the last available follow-up. Atrophy was measured by 2 graders using the region finder software on Heidelberg Explorer and confirmed using OCT scans covering the entire atrophic lesion. The following imaging biomarkers were analyzed at each visit: foveal atrophy, vitreomacular traction, outer retinal tubulations, choroidal caverns and subfoveal choroidal thickness, border autofluorescence pattern (hyper-autofluorescent or iso-autofluorescent), and border irregularity as expressed by circularity index (CI).Main Outcome MeasuresPrimary outcomes were annual rate of atrophy enlargement and BCVA loss in EMAP patients. Secondary outcomes included the assessment of potential factors able to predict disease progression.ResultsThirty-six eyes from 18 patients with EMAP (6 men [33%]; mean age at symptom onset, 48.1 ± 1.7 years) were included. Mean follow-up lasted 32.8 ± 14.3 months. RPE atrophy increased from 10.8 ± 6.3 mm2 at baseline to 18.1 ± 8.3 mm2 at the end of follow-up, with a rate of 2.91 ± 1.09 mm2/year. Faster progression was associated with smaller CI at baseline (P = 0.02) and with iso-autofluorescent lesion borders (P = 0.01). Visual acuity declined progressively at a rate of 7.4 ± 5.8 letters per year, with 57% of eyes showing vision of 20/200 Snellen or worse at the 4-year follow-up. Worse visual outcomes were observed in patients with early foveal involvement at baseline (P = 0.02).ConclusionsPatients affected by EMAP present a rapid expansion of RPE atrophy that is comparable with the diffuse-trickling form of geographic atrophy. More irregular and iso-autofluorescent lesion borders seem to predict faster progression. Our findings may provide relevant information for patient counseling and future interventional approaches to select the best candidates and proper clinical outcomes.

Long-Term Safety Evaluation of Continuous Intraocular Delivery of Aflibercept by the Intravitreal Gene Therapy Candidate ADVM-022 in Nonhuman Primates

PurposeTo evaluate the long-term safety of vascular endothelial growth factor (VEGF) suppression with sustained aflibercept expression after a single intravitreal injection (IVI) of ADVM-022, an anti-VEGF gene therapy, in non-human primates (NHPs).MethodsNon-human primates received bilateral IVI of ADVM-022, a gene therapy vector encoding aflibercept, a standard of care for the treatment of VEGF-based retinal disease. Aflibercept levels from ocular fluids and tissues were measured. Ocular inflammation was assessed by slit lamp biomicroscopy and fundoscopy. The integrity of the retinal structure was analyzed by optical coherence tomography and blue light fundus autofluorescence and electroretinography was performed to determine retinal function. Histologic evaluation of the retina was performed at the longest time point measured (2.5 years after injection).ResultsSustained expression of aflibercept was noted out to the last time point evaluated. Mild to moderate inflammatory responses were observed, which trended toward spontaneous resolution without anti-inflammatory treatment. No abnormalities in retinal structure or function were observed, as measured by optical coherence tomography and electroretinography, respectively. RPE integrity was maintained throughout the study; no histologic abnormalities were observed 2.5 years after ADVM-022 IVI.ConclusionsIn non-human primates, long-term, sustained aflibercept expression and the resulting continuous VEGF suppression by a single IVI of ADVM-022, appears to be safe, with no measurable adverse effects on normal retinal structure and function evaluated out to 2.5 years.Translational RelevanceTogether with the results from previous ADVM-022 preclinical studies, these data support the evaluation of this gene therapy candidate in clinical trials as a potential durable treatment for various VEGF-mediated ophthalmic disorders.