Late-phase Indocyanine Green Angiography Research Articles

NATURAL COURSE OF AGE-RELATED RETENTIONAL AVASCULAR PIGMENT EPITHELIAL DETACHMENT: Support For The Lipid Barrier Hypothesis.

Retentional pigment epithelial detachment (PED) associated with age-related scattered hypofluorescent spots on late-phase indocyanine green angiography (ASHS-LIA) is hypothesized to be caused by Bruch membrane's lipid barrier. This study aimed to report the natural course of retentional PED and evaluate the relationship between retentional PED evolution and ASHS-LIA. Patients with treatment-naïve retentional PED were enrolled and observed every 3 months for at least 12 months. Treatment was not performed except for secondary macular neovascularization. In 55 studied eyes with a median follow-up of 18.0 (range: 12-36) months, 87.3% (48/55) of the retentional PEDs persisted, 7.3% (4/55) resolved, and 5.5% (3/55) progressed to polypoidal choroidal vasculopathy. The mean PED area significantly increased during the follow-up ( P < 0.001) and with the ASHS-LIA grade at each follow-up point (all P <0.05), especially during the first 6 months before approaching the edge of confluent ASHS-LIA. Persistent PEDs were mostly stable (52.1%) or enlarged (45.8%) but reduced in only 1 case (2.1%) because of retinal pigment epithelium microrip at the edge of PED. The persistent PEDs were all within the ASHS-LIA region, especially the macular confluence region. The resolved PEDs all had grade 1 ASHS-LIA and resolved after gradual expansion of PED beyond the confluent ASHS-LIA region. Pigment epithelial detachments that progressed to macular neovascularization all had confluent grade 2 or 3 ASHS-LIA. Retinal pigment epithelium microrips or apertures within PED did not affect the progression of the PED. The natural course of retentional PED is closely related to the features of ASHS-LIA and supports its lipid-barrier hypothesis.

Translating color fundus photography to indocyanine green angiography using deep-learning for age-related macular degeneration screening

Age-related macular degeneration (AMD) is the leading cause of central vision impairment among the elderly. Effective and accurate AMD screening tools are urgently needed. Indocyanine green angiography (ICGA) is a well-established technique for detecting chorioretinal diseases, but its invasive nature and potential risks impede its routine clinical application. Here, we innovatively developed a deep-learning model capable of generating realistic ICGA images from color fundus photography (CF) using generative adversarial networks (GANs) and evaluated its performance in AMD classification. The model was developed with 99,002 CF-ICGA pairs from a tertiary center. The quality of the generated ICGA images underwent objective evaluation using mean absolute error (MAE), peak signal-to-noise ratio (PSNR), structural similarity measures (SSIM), etc., and subjective evaluation by two experienced ophthalmologists. The model generated realistic early, mid and late-phase ICGA images, with SSIM spanned from 0.57 to 0.65. The subjective quality scores ranged from 1.46 to 2.74 on the five-point scale (1 refers to the real ICGA image quality, Kappa 0.79–0.84). Moreover, we assessed the application of translated ICGA images in AMD screening on an external dataset (n = 13887) by calculating area under the ROC curve (AUC) in classifying AMD. Combining generated ICGA with real CF images improved the accuracy of AMD classification with AUC increased from 0.93 to 0.97 (P < 0.001). These results suggested that CF-to-ICGA translation can serve as a cross-modal data augmentation method to address the data hunger often encountered in deep-learning research, and as a promising add-on for population-based AMD screening. Real-world validation is warranted before clinical usage.

Value and Significance of Hypofluorescent Lesions Seen on Late-Phase Indocyanine Green Angiography

The hypofluorescence of fundus lesions observed during the late phase of indocyanine green angiography (ICGA) in various diseases has often been overlooked or misinterpreted. This article explores the significance of fundus lesions that are initially isofluorescent during the early phase of ICGA but become hypofluorescent later in the examination. Pathologies such as multiple evanescent white spot syndrome, acute posterior placoid syphilitic chorioretinitis, chronic central serous chorioretinopathy, choroidal hemangioma, and some fundus with drusen, present this phenomenon of late hypofluorescence. The interpretation of ICGA images and the role of indocyanine green (ICG) uptake by the retinal pigment epithelium (RPE) in late fundus fluorescence is debated. Experimental evidence suggests that ICG accumulates progressively in the RPE after intravenous injection of the dye or after direct contact invitro, making it a potential marker of RPE activity. Although the exact mechanisms of ICG diffusion through the choroid and its binding to the RPE require further investigation, the late hypofluorescence observed in certain ICGA diseases provides information on different modalities of RPE dysfunction. The author has no proprietary or commercial interest in any materials discussed in this article.

PUNCTATE INNER PACHYCHOROIDOPATHY: Demographic and Clinical Features of Inner Choroidal Inflammation in Eyes with Pachychoroid Disease.

To perform an unsupervised machine learning clustering of patients with punctate inner choroidopathy (PIC) and provide new insights into the significance of pachychoroid disease features in PIC eyes. Retrospective multicenter study, including 102 eyes from 82 patients diagnosed with PIC. Demographics, clinical data, and multimodal imaging, including fundus photography, optical coherence tomography, and indocyanine green angiography, were collected. Clusters of eyes were identified, and multilevel logistic regression analysis was performed to compare between-group differences. Using 17 clinical features, two distinct clusters of patients with PIC were identified. Cluster 1 patients were characterized by older age, high myopia, myopic maculopathy features, thin choroids, multiple lesions, and a higher likelihood of developing patchy chorioretinal atrophy. Cluster 2 consisted of younger age, emmetropia or low myopia, thick choroids, choroidal vascular hyperpermeability on late-phase indocyanine green angiography, and high prevalence of focal choroidal excavation. These features exhibited significant differences ( P < 0.05) between the two clusters. While PIC typically affects young myopic female patients with thin choroids, a subset of patients with PIC exhibits features associated with pachychoroid disease. Considering the potential influence of choroidal venous insufficiency on PIC manifestations and secondary complications, we propose the term "punctate inner pachychoroidopathy" to characterize this distinct subtype of PIC.

Hyperfluorescence of choroidal arteries in the peripheral fundus on late-phase ICGA.

To correlate the hyperfluorescent lines in the peripheral fundus on late-phase indocyanine green angiography (ICGA) to infrared and optical coherence tomography (OCT) findings. This is a retrospective, cross-sectional study. Multimodal imaging data, including ICGA, fluorescein angiography, infrared imaging, and OCT were analyzed. The hyperfluorescent lines were categorized into 2 grades according to their extents. In addition, serum levels of apolipoprotein (Apo) A and B were measured by enzyme linked immunosorbent assay. A total of 247 patients who underwent multimodal imaging were reviewed. The hyperfluorescent lines in the peripheral fundus on late-phase ICGA were detected in 96 patients, and were correlated to superficial choroidal arteries by infrared imaging and OCT. The incidence of hyperfluorescent choroidal arteries in the peripheral fundus (HCAP) on late-phase ICGA increased in groups of older ages (0-20 years, 4.3%; 20-40 years, 2.6%; 40-60 years, 48.9%; >60 years, 88.7%; p < 0.001). In addition, the mean age increased with the grades of HCAP (grade 1, 52.3 ± 10.8 years; grade 2, 63.3 ± 10.5 years; p < 0.001). The hyperfluorescence was also detected in posterior choroidal arteries in 11 eyes, all patients in grade 2. There was no significant correlation between grades of HCAP and gender, or serum level of ApoA and ApoB. The occurrence and grades of HCAP increased with age. The superficial location of choroidal arteries in the peripheral fundus exposes their hyperfluorescence on late-phase ICGA. HCAP might reveal the local lipid degeneration of choroidal artery walls, according to ICG binding properties.

Indocyanine green angiography of type 1 macular neovascularization in age-related macular degeneration and central serous chorioretinopathy reveals different disease mechanisms.

To assess the rate of late phase hyperfluorescent plaque (LPHP) in type 1 macular neovascularization (MNV) in CSCR (central serous chorioretinopathy) and AMD (age-related macular degeneration) and to evaluate its prognostic value. Retrospective study including type 1 MNV in AMD and CSCR, from 2012 to 2020. Eyes with a late ICG-A image (>20mins) and clear visualization of MNV on OCTA were included. Quantitative and qualitative parameters on OCT and best corrected visual acuity were recorded at baseline, and after 3 monthly anti-VEGF injections. Eighty-three eyes were included, 35 with CSCR and 48 with AMD. Patients in the CSCR group were significantly younger than in the AMD group (61.3 ± 10.4 vs. 80.2 ± 6.8 years respectively, p<0.001), predominantly male (68.6% CSCR vs 35.4% AMD; p=0.003) and with a thicker choroid (379 ± 93.3 μm vs 204.2 ± 93.2 μm; p<0.001). Type 1 MNV in CSCR showed fewer LPHP compared to AMD (31.4% vs 77.1%; p<0.001). Baseline visual acuity was lower in patients with LPHP (0.37± 0.22 vs 0.27 ±0.28 LogMAR, p=0.03). On multivariate analysis, AMD was associated with the presence of LPHP (p<0.001). No significant difference in the response to anti-VEGF was observed. Leakage of macromolecules from MNV and accumulation in the RPE and/or in the stroma imaged by the LPHP is less common in eyes with type 1 MNV in CSCR than in AMD. Late phase ICG-A imaging offers an insight into the metabolism of the dye and the environment surrounding the neovascular membrane.

Telangiectatic Capillaries in Retinal Vascular Occlusions: Multimodal Imaging in a Case Series.

Introduction: To report a cases series of retinal vascular occlusions with telangiectatic capillaries (TelCaps) seen on indocyanine green angiography (ICGA) and multimodal imaging. Methods: In this case series, a new finding (TelCaps) was seen on clinical examination, fundus evaluation, fluorescein angiography, ICGA, and optical coherence tomography (OCT). Results: This series comprised 3 patients with TelCaps findings on ICGA after retinal vascular occlusions. The patients' ages ranged from 52 years to 71 years and the best-corrected visual acuity in the affected eye, from 20/25 to 20/80. Fundus evaluation showed small, hard exudates in the vascular termination close to the macula with a reduction of the foveal reflex. The OCT images showed marginal hyperreflectivity and inner hyporeflectivity that were suggestive of a TelCaps lesion, which was confirmed by hyperfluorescence in the late phase of ICGA. Conclusions: This study highlights the importance of performing multimodal imaging evaluation, including ICGA, in eyes with retinal vein occlusions for early identification and management of the associated lesions.

COMPARISON OF PRIMARY AND SECONDARY FORMS OF MULTIPLE EVANESCENT WHITE DOT SYNDROME.

The aim of this study was to compare primary versus secondary forms of multiple evanescent white dot syndrome (MEWDS) at T0 (baseline) and T1 (1-4 months after the onset of symptoms). A total of 101 eyes in 100 patients were included in a multicentric retrospective study. Secondary MEWDS was defined as MEWDS associated with underlying chorioretinal inflammatory pathologies, mainly multifocal choroiditis and punctuate inner choroidopathy. Patients with secondary MEWDS were older (P = 0.011). The proportion of women (P = 0.8), spherical equivalent (P = 0.3), and best-corrected visual acuity at T0 (P = 0.2) were not significantly different between the two groups. The area of MEWDS lesions on late-phase indocyanine green angiography was significantly smaller in secondary MEWDS (P = 0.001) and less symmetrical with respect to both horizontal (P = 0.003) and vertical (P = 0.004) axis. At T0, neither the clinical (P = 0.5) nor the multimodal imaging (P = 0.2) inflammation scores were significantly different between the groups. At T1, the multimodal imaging inflammation score was higher in secondary MEWDS (P = 0.021). In secondary MEWDS, outer retinal lesions are less extensive and located close to preexisting chorioretinal lesions. Mild signs of intraocular inflammation on multimodal imaging are more frequent in secondary MEWDS during recovery. These findings suggest that chorioretinal inflammation may trigger secondary MEWDS.

CHOROIDAL AMYLOID DEPOSITION: A Multicenter Study of Amyloid Lesions Identified in Late Indocyanine Green Angiography.

To characterize choroidal amyloid angiopathy (CAA) using late-phase indocyanine green angiography (ICGA). This was a multicenter retrospective observational case series on patients with transthyretin (ATTR) and AL amyloidosis who underwent ICGA. The timing of hyperfluorescence and longitudinal changes were analyzed. Thirty-two patients (27 with ATTR and 5 with AL) with mean age of 58.9 ± 17.4 years were included. Hyperfluorescent spots in the very late phases of ICGA, corresponding to CAA, were observed in 49 of 55 eyes (89%). The median time to maximal staining was 672 (95% confidence interval, 644-752) seconds, which was significantly later than the initial staining (503 [95% confidence interval, 447-521], P < 0.0001; Wilcoxon signed rank test). In seven patients with ATTR amyloidosis who underwent follow-up of ICGA, the CAA was stable in two patients and improved in five patients during treatment. However, 3 patients (43%) had worsening vitreous opacities in both eyes, and 4 patients (57%) developed secondary open-angle glaucoma. Most patients with amyloidosis were found to have CAA on ICGA. Up to 12.5 minutes is required for maximal ICG staining. Choroidal amyloid angiopathy improved in most patients with systemic treatment and may serve as a marker of systemic disease status.

Ageing fundus degenerations of Macaca fascicularis on multi-modal imaging and histopathology: Similarities and differences compared to human

To characterize the ageing fundus degenerations in Macaca fascicularis, we used multimodal imaging including color fundus photograph, spectral domain optical coherence tomography, fundus autofluorescence, fundus fluorescence angiography, and indocyanine green angiography (ICGA) to survey and track fundus changes of 84 Macaca fascicularis, ranging from 5 to 24 years old over 2 years, and followed by hematoxylin-eosin (HE) and immunofluorescence (IF) staining. The Macaca fascicularis in our cohort showed ageing characteristics different from human, including the more common yellow dot maculopathy, the unique appearance of patchy hyperautoflurescence, and the absence of subretinal drusenoid deposit, basal laminar deposit, geographic atrophy or choroidal neovascularization. Same with human, hard drusen, soft drusen, atherosclerosis, tessellated retina, staining of vessels in peripheral choroid on late-phase ICGA, and peripheral hard drusen were detected. HE and IF staining suggested the patchy hyperautoflurescence to be drusenoid deposits. BMI were significantly higher in the Macaca fascicularis with yellow dot maculopathy and hard drusen, compared to the ones without (p < 0.05). Our study reveals fundus degenerations that develop with ageing in the nonhuman primate of Macaca fascicularis. Their differences and similarities compared to human worth notice by future translational research in degenerative fundus diseases, especially age-related macular degeneration.

AGE-RELATED RETENTIONAL AVASCULAR PIGMENT EPITHELIAL DETACHMENT VIEWED WITH INDOCYANINE GREEN ANGIOGRAPHY.

Age-related scattered hypofluorescent spots on late-phase indocyanine green angiography (ASHS-LIA) might represent hydrophobic neutral lipid deposits in the Bruch membrane. This study aimed to report retentional avascular pigment epithelial detachment (PED) associated with ASHS-LIA. Patients aged ≥50 years who presented a single avascular serous PED without soft drusen or any other retinal or choroidal diseases were retrospectively included. Pigment epithelial detachment was classified as retentional, effusional, or mixed PED based on indocyanine green angiography. Multimodal images were qualitatively and quantitatively evaluated. This study included 74 eyes of 57 patients. Retentional PED, effusional PED, and mixed PED accounted for 91.9%, 4.1%, and 4.1%, respectively. All PEDs were located in the macular region. Seventeen (29.8%) included patients had bilateral PEDs and all were retentional PEDs with a high level of bilateral consistency in the characteristics of PED and ASHS-LIA. All retentional PEDs were within the bounds of ASHS-LIA. The area of retentional PED increased with the ASHS-LIA grade ( P = 0.030). Most age-related avascular serous PEDs are retentional PEDs. The location and area of retentional PEDs are consistent with the distribution of ASHS-LIA. These findings suggest that the hydrophobic neutral lipid deposits in the Bruch membrane might be involved in the pathogenesis and be a therapeutic target in age-related retentional avascular PED.

Visualizing lipid behind the retina in aging and age-related macular degeneration, via indocyanine green angiography (ASHS-LIA).

Age-related macular degeneration (AMD) causes legal blindness in older adults worldwide. Soft drusen are the most extensively documented intraocular risk factor for progression to advanced AMD. A long-standing paradox in AMD pathophysiology has been the vulnerability of Asian populations to polypoidal choroidal vasculopathy (PCV) in the presence of relatively few drusen. Age-related scattered hypofluorescent spots on late phase indocyanine green angiography (ASHS-LIA) was recently proposed as precursors of PCV. Herein, we offer a resolution to the paradox by reviewing evidence that ASHS-LIA indicates the diffuse form of lipoprotein-related lipids accumulating in Bruch's membrane (BrM) throughout adulthood. Deposition of these lipids leads to soft drusen and basal linear deposit (BLinD), a thin layer of soft drusen material in AMD; Pre-BLinD is the precursor. This evidence includes: 1. Both ASHS-LIA and pre-BLinD/BLinD accumulate in older adults and start under the macula; 2. ASHS-LIA shares hypofluorescence with soft drusen, known to be physically continuous with pre-BLinD/BLinD. 3. Model system studies illuminated a mechanism for indocyanine green uptake by retinal pigment epithelium. 4. Neither ASHS-LIA nor pre-BLinD/ BLinD are visible by multimodal imaging anchored on current optical coherence tomography, as confirmed with direct clinicopathologic correlation. To contextualize ASHS-LIA, we also summarize angiographic characteristics of different drusen subtypes in AMD. As possible precursors for PCV, lipid accumulation in forms beyond soft drusen may contribute to the pathogenesis of this prevalent disease in Asia. ASHS-LIA also might help identify patients at risk for progression, of value to clinical trials for therapies targeting early or intermediate AMD.

Indocyanine Green Angiography Features in Acute Syphilitic Posterior Placoid Chorioretinitis

Acute syphilitic posterior placoid chorioretinitis (ASPPC) is a rare clinical manifestation of ocular syphilis. The cause of the placoid lesion is still up for debate but could be caused by an impaired choriocapillaris perfusion. However, less attention has been paid to the hypofluorescence of the plaque on late-phase indocyanine green angiography (ICGA). The aim of this study was to comprehensively analyze multimodal imaging findings in patients with ASPPC and to highlight the value of ICGA for the diagnosis of ASPPC. Retrospective observational case study. The medical records of patients with uveitis who consulted our tertiary center between 2012 and December 2015 were reviewed. Patients who were diagnosed with uveitis related to syphilis infection with posterior placoid lesions seen on multimodal imaging were included. We compared the aspect of ASPPC on fundus color photography, blue autofluorescence, fluorescein angiography, optical coherence tomography, and early-, mid- and late-phase ICGA. Fifteen eyes of 12 patients were included in the study. Hypofluorescent plaques were seen on late-phase ICGA in all eyes, corresponding to the placoid lesions visible on blue autofluorescence, while the choriocapillaris filling was normal on fluorescein angiography and ICGA. Within the plaques, optical coherence tomography showed ellipsoid zone disruptions, outer retinal disruptions, and retinal pigment epithelium granulations. ASPPC could be caused by retinal pigment epithelium dysfunction secondary to an infectious or inflammatory disorder, characterized by a hypofluorescence visible only on late-phase ICGA, and resulting in photoreceptor disruptions. The RPE impairment was reversible after prompt antibiotic treatment.

Choroidal vascular alterations evaluated by ultra-widefield indocyanine green angiography in central serous chorioretinopathy.

This study aims to evaluate choroidal vascular alterations in patients with central serous chorioretinopathy (CSC) using ultra-widefield (UWF) indocyanine green angiography (ICGA). This was a retrospective case-control study conducted at a single tertiary eye center. In total, 36 eyes in patients with either unilateral (24 patients) or bilateral (six patients) treatment-naïve CSC and 30 eyes in 24 age-matched controls were evaluated. The number of quadrants with vortex vein engorgement on UWF ICGA was evaluated. Dilated choroidal vessels affecting the macula were regarded as extended vortex vein engorgement. Choroidal vascular hyperpermeability (CVH) area on late-phase ICGA was quantified using stereographic projection. The parameters were compared with clinical and optical coherence tomographic findings. Eyes with CSC had larger CVH area, thicker choroid, and more quadrants with vortex vein engorgement and extended vortex vein engorgement compared with control eyes (all P < 0.001). In patients with unilateral CSC, affected eyes had larger CVH area, thicker choroid, and more extended vortex vein engorgements compared with unaffected fellow eyes (all P < 0.001), but vortex vein engorgement did not significantly differ. CVH was significantly correlated with extended vortex vein engorgement (P < 0.001) and subfoveal choroidal thickness (P = 0.007). The increased number and binocular symmetry of engorged vortex veins suggest an anatomical predisposition for CSC. CVH area and extended vortex vein engorgement were indicators of choroidal outflow congestion. These parameters may serve as diagnostic clues or predictors of disease development in eyes with CSC.

Retinal Diseases Regulated by Hypoxia-Basic and Clinical Perspectives: A Comprehensive Review.

In recent years, the number of patients with age-related macular degeneration (AMD) is increasing worldwide along with increased life expectancy. Currently, the standard treatment for wet-AMD is intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. The upstream of VEGF is hypoxia-inducible factor (HIF), a master regulator of hypoxia-responsive genes responsive to acute and chronic hypoxia. HIF activation induces various pathological pro-angiogenic gene expressions including VEGF under retinal hypoxia, ultimately leading to the development of ocular ischemic neovascular diseases. In this regard, HIF is considered as a promising therapeutic target in ocular ischemic diseases. In clinical ophthalmology, abnormal hypofluorescent areas have been detected in the late-phase of indocyanine green angiography, which are thought to be lipid deposits at the level of Bruch’s membrane to choriocapillaris in vitreoretinal diseases. These deposits may interfere with the oxygen and nutrients that should be supplied to the retinal pigment epithelium, and that HIF/VEGF is highly suspected to be expressed in the hypoxic retinal pigment epithelium, leading to neovascularization. In this review, we comprehensively summarize pathophysiology of AMD-related ocular diseases with the HIF/VEGF pathway from basic and clinic researches with recent findings.

Assessment of Hypofluorescent Foci on Late-Phase Indocyanine Green Angiography in Central Serous Chorioretinopathy.

To assess the hypofluorescent foci (HFF) on late-phase indocyanine green angiography (ICGA) in central serous chorioretinopathy (CSC) using short-wavelength fundus autofluorescence (SW-FAF), near-infrared autofluorescence (NIR-AF), and fluorescein angiography (FA). The HFF area on late-phase ICGA for at least 20 min was compared with the area of abnormal foci on SW-FAF, NIR-AF, and FA. In 14 consecutive patients (12 men, including 1 with bilateral CSC; and 2 women with unilateral CSC), four kinds of images of 27 eyes were acquired. The mean age ± standard deviation (range) was 46 ± 9.2 years (31–69 years). The HFF on late-phase ICGA were found in 23 eyes (in all 15 CSC eyes and the contralateral 8 eyes). From the results of simple regression analysis, we obtained the following three formulas. The HFF area on ICGA = 1.058 × [abnormal SW-FAF area] + 0.135, the HFF area on ICGA = 1.001 × [abnormal NIR-AF area] + 0.015, and the HFF area on ICGA = 1.089 × [abnormal FA area] + 0.135. Compared to SW-FAF and FA, NIR-AF was found to be the easiest method to detect the HFF on late-phase ICGA, which may indicate melanin abnormalities, especially a decrease, in the retinal pigment epithelium.

Choroidal Vascular Abnormalities by Ultra-widefield Indocyanine Green Angiography in Polypoidal Choroidal Vasculopathy

PurposeTo evaluate vortex vein engorgement and choroidal vascular hyperpermeability in patients with polypoidal choroidal vasculopathy (PCV) using ultra-widefield indocyanine green angiography (ICGA).MethodsThis retrospective case control study included 51 patients with unilateral PCV, 7 patients with bilateral PCV, and 43 age-matched controls. The number of quadrants of vortex vein engorgement was evaluated in the middle phase of ICGA, which was classified as extended engorgement if the dilated choroidal vessels expanded to the macula. The area of choroidal vascular hyperpermeability was quantified stereographically from the late-phase ICGA and correlated with clinical and optical coherence tomography findings.ResultsAffected eyes had a larger choroidal hyperpermeability area and a thicker subfoveal choroid than eyes in the control group or fellow eyes (P < 0.001, P < 0.001). More quadrants with extended vortex vein engorgement were observed in affected eyes than in fellow eyes (P < 0.001). Significant differences were observed in the area of choroidal hyperpermeability, Haller layer thickness and greatest linear dimension according to the extended vortex vein engorgement in eyes with PCV (P < 0.001, P = 0.001, and P = 0.001, respectively). The area of choroidal hyperpermeability was significantly correlated with subfoveal choroidal thickness (P < 0.001, Pearson's correlation coefficient = 0.471).ConclusionsUltra-widefield ICGA results revealed that patients with PCV had vortex vein engorgement and an increased choroidal hyperpermeability area. The results from this study provide substantial information to clarify the pathogenesis and predict the prognosis in the patients with PCV.

The Natural History of Bruch’s Membrane Calcification in Pseudoxanthoma Elasticum

PurposeTo describe the natural history of Bruch’s membrane (BM) calcification in patients with pseudoxanthoma elasticum (PXE).DesignRetrospective cohort study.ParticipantsBoth eyes of 120 PXE patients younger than 50 years, 78 of whom had follow-up imaging after more than 1 year.MethodsAll patients underwent multimodal imaging, including color fundus photography, near-infrared reflectance (NIR) imaging, and late phase indocyanine green angiography (ICGA). We determined the distance from the optic disc to the central and temporal border of peau d’orange on NIR, expressed in horizontal optic disc diameter (ODD). The length of the longest angioid streak was classified into 5 zones.Main Outcome MeasuresAge-specific changes of peau d’orange, angioid streaks, and ICGA hypofluorescence as surrogate markers for the extent of BM calcification.ResultsIn cross-sectional analysis, longer angioid streaks were associated with increasing age (P < 0.001 for trend). The temporal border of peau d’orange showed a weak association with increasing age (β = 0.02; 95% confidence interval [CI], 0.00–0.04), whereas the central border showed a strong association (β = 0.12; 95% CI, 0.09–0.15). Longitudinal analysis revealed a median shift of the central border to the periphery of 0.08 ODD per year (interquartile range [IQR], 0.00–0.17; P < 0.001). This shift was more pronounced in patients younger than 20 years (0.12 ODD per year [IQR, 0.08–0.28]) than in patients older than 40 years (0.07 ODD per year [IQR, –0.05 to 0.15]). The temporal border did not shift during follow-up (P = 0.69). New or growing angioid streaks were detected in 39 of 156 eyes (25%). The hypofluorescent area on ICGA was visible only in the fourth or fifth decade and correlated with longer angioid streaks.ConclusionsIn PXE patients, the speckled BM calcification slowly confluences during life. The location of the temporal border of peau d’orange remains rather constant, whereas the central border shifts to the periphery. This suggests the presence of a predetermined area for BM calcification. A larger ICGA hypofluorescent area correlates with older age and longer angioid streaks, which implies that it depends on the degree of BM calcification.

Fundus autofluorescence of retinal angiomatous proliferation.

PurposeThe present study aimed to evaluate the characteristics of fundus autofluorescence in Japanese patients with retinal angiomatous proliferation (RAP).MethodsWe retrospectively reviewed 100 eyes from 76 patients (male, n = 45; female, n = 31; age range, 50–94 years; mean ± standard deviation, 81.4 ± 6.4 years) with treatment-naïve RAP, which was diagnosed based on the identification of retinal–retinal anastomosis on early-phase fluorescein angiography or indocyanine green angiography (ICGA) and the identification of a hot spot on late-phase ICGA. RAP was classified into the following three stages: stage 1, proliferation of intraretinal capillaries originating from the deep retinal complex (intraretinal neovascularization); stage 2, growth of the retinal vessels into the subretinal space (subretinal neovascularization); and stage 3, clinically or angiographically observed choroidal neovascularization. In all cases, short-wavelength and near-infrared autofluorescence (SW-AF, NIR-AF) was evaluated using a confocal scanning laser ophthalmoscope.ResultsThe conditions of the 100 eyes were as follows: stage 1 RAP, n = 6 (6%); stage 2 RAP without retinal pigment epithelial detachment (PED), n = 40 (40%); stage 2 RAP with PED, n = 44 (44%); and stage 3 RAP, 10 (10%). On NIR-AF imaging, the number of abnormalities that were observed to correspond to the RAP lesions on ICGA (87 eyes, 87%) was significantly greater in comparison to SW-AF imaging (27 eyes, 27%). The mean follow-up period in all 76 patients was 39.2 months. In the 76 patients with unilateral disease, 21 (21%) eyes developed RAP in the fellow eye during the follow-up period. Among 18 eyes that were examined by both SW-AF and NIR-AF imaging before the onset of RAP lesions, NIR-AF imaging showed hypoautofluorescence in 15 (83%) eyes before the onset of RAP lesions.ConclusionsSW-AF and NIR-AF abnormalities may be related to the dysfunction of the photoreceptor/retinal pigment epithelium complex. Hypoautofluorescence on NIR-AF imaging may accurately indicate the presence or onset of RAP lesions.

Late-phase hypercyanescence during indocyanine green angiography for assessment of myopic choroidal neovascularization.

Indocyanine green angiography (ICGA) is a major diagnostic modality but the clinical implications of specific staining patterns in active myopic choroidal neovascularization (mCNV) are unclear. We examined the associations of ICGA cyanofluorescence patterns with disease characteristics and response to an as-needed intravitreal ranibizumab (IVR) treatment regimen among active mCNV patients. Twenty-four subjects with active mCNV treated by IVR were enrolled in this retrospective cohort study. Information from medical records were reviewed, including best corrected visual acuity (BCVA), fluorescein angiography (FA) findings, ICGA cyanofluorescence patterns, and spectral-domain OCT (SD-OCT) results. The CNV lesion size, CNV thickness, and central retinal thickness (CRT) were measured from these images. Two staining patterns were identified on late-phase ICGA images, hypercyanescence (9/24, 37.5%) and non-hypercyanescence (15/24, 62.5%). There were no differences in baseline BCVA, CNV thickness, and CRT between ICGA pattern groups; however, the hypercyanescence group demonstrated a larger CNV lesion size (p = 0.035) and required more IVR injections than the non-hypercyanescence group (2.67 ± 1.58 vs 1.07 ± 0.27, p = 0.016), while the non-hypercyanescence group demonstrated better final BCVA improvement (p = 0.041). Hypercyanescence could be divided into two types, a uniform type and rim type. A pseudopodia-like protrusion of CNV enlargement with a rim-enhanced type hypercyanescence at the protrusion rim was predictive of required retreatment. Hypercyanescence on late-phase ICGA may assist in identifying more active mCNV requiring intensive treatment.