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Purpose: To report a case of recurrent acute retinopathy associated with pseudoxanthoma elasticum and to propose a reappraisal of this entity based on multimodal imaging analysis., Methods: Retrospective case report. High-resolution optical coherence tomography (high-res OCT), ultra-widefield imaging, and widefield swept-source OCT angiography and en face OCT were performed., Results: A man in his 40s diagnosed with pseudoxanthoma elasticum and angioid streaks presented with two distinct episodes of acute retinopathy in his right eye during a one-year follow-up period. Acute retinopathy was characterized by rapid vision loss. High-res OCT showed multifocal hyperreflective lesions splitting the retinal pigment epithelium/Bruch membrane complex and associated with focal choroidal thickening. After the first episode, OCT angiography confirmed the development of macular neovascularization at the site of a previous inflammatory lesion. During the second episode, multimodal images showed findings consistent with epiphenomenon multiple evanescent white dot syndrome (EpiMEWDS). On en face widefield OCT, acute retinopathy was characterized by multiple hyperreflective spots scattered at the posterior pole., Conclusion: Recurrence of acute retinopathy can be observed in patients with pseudoxanthoma elasticum and angioid streaks. Multimodal imaging shows that some lesions of pseudoxanthoma elasticum-associated acute retinopathy closely resemble those of punctate inner choroidopathy/idiopathic multifocal choroiditis., Competing Interests: K.B. Freund is a consultant for Heidelberg Engineering, Zeiss, Genentech, Bayer, Novartis, and Allergan. He receives research support from Genentech/Roche. The authors declare that there is no conflict of interest regarding the publication of this article.

Background: Pseudoxanthoma elasticum (PXE) is an autosomal recessive condition caused by mutations in the ABCC6 gene. Ocular features include angioid streaks, peau d'orange fundus, and drusen. We report a novel ABCC6 mutation causing PXE in a patient with a mixed phenotype of PXE and retinitis pigmentosa (RP)., Case: A 37-year-old female presented with decreased peripheral vision and nyctalopia. Ocular imaging revealed angioid streaks emanating from the optic nerve as well as peripheral pigmentary changes and bone spicules. Genetic testing revealed two mutations in ABCC6 in trans. No other mutation was identified., Conclusion: We present a rare case with ocular findings of PXE and RP in a patient with a novel ABCC6 mutation. The patient presented both with peripheral pigmentary changes and angioid streaks. Further investigation into this novel mutation would be beneficial to determine if the mutation is involved in the RP phenotype.

Purpose: To describe the steps leading to the development and progression of macular neovascularization (MNV) in angioid streaks., Methods: The study was designed as retrospective, longitudinal case series. Patients with angioid streaks were investigated by means of multimodal imaging, including fundus autofluorescence and structural optical coherence tomography. Main outcome measures were hyperreflective foci and MNV progression steps., Results: Overall, 40 eyes (20 patients) affected by angioid streaks were evaluated. Over the follow-up, five eyes of five patients developed MNV. The mean follow-up was of 1.6 years. The mean number of anti-vascular endothelial growth factor injections was 4.35 ± 1.4. Mean best-corrected visual acuity was 0.53 ± 0.38 LogMAR at the MNV onset, improving to 0.42 ± 0.40 LogMAR at the end of the follow-up ( P > 0.05). Intraretinal hyperreflective foci onset and coalescence represented the first alterations occurring before the onset of the MNV. Anti-vascular endothelial growth factor treatment was associated with exudation relapsing and remitting, with still present intraretinal hyperreflective foci and pigment accumulation. The longitudinal analysis of our cohort of eyes outlined the event timeline: 1.2 months to find concentrated hyperreflective foci, 4.5 months to observe pigment organization through the outer nuclear layer, and 1.5 years to detect MNV., Conclusion: Hyperreflective foci formation, concentration, and migration represent early alterations occurring before the onset of the MNV in angioid streaks.

Purpose: To report the very long-term visual prognosis of choroidal neovascularization complicating angioid streaks in the antivascular endothelial growth factor era., Methods: Retrospective monocentric study aimed at analyzing patients' demographics, choroidal neovascularization features, angioid streak-associated conditions, and previous and current therapies for choroidal neovascularization. The main outcome measures were the quantitative measurement of central retinal pigment epithelial atrophy enlargement by comparing the ratio of pixels involved on automated infrared images acquired by spectral-domain optical coherence tomography and the changes in best-corrected visual acuity. The secondary outcome measures were the number of intravitreal injections and the changes in central choroidal thickness and central retinal thickness. Subgroup analyzes were performed to compare macular atrophy extent between eyes of patients with or without proven pseudoxanthoma elasticum ("PXE" or "no PXE") and between eyes previously treated or not with photodynamic therapy ("PDT" or "no PDT")., Results: Thirty-three eyes of 23 patients were included. The mean best-corrected visual acuity decreased significantly from 66 ± 19 Early Treatment Diabetic Retinopathy Study letters at the time of the first antivascular endothelial growth factor injection to 52 ± 23 Early Treatment Diabetic Retinopathy Study letters at the end of the follow-up (mean follow-up duration: 109 ± 42 months, range: 47-175 months). The ratio of central retinal pigment epithelial atrophy enlargement was 201%, 110%, 240%, and 111% in the PXE, no PXE, PDT, and no PDT groups, respectively., Conclusion: Despite the use of antivascular endothelial growth factor agents, the very long-term prognosis appeared relatively poor, especially in patients with PXE. This study also suggests that PDT should be used with caution in the management of choroidal neovascularization in eyes with angioid streaks., Competing Interests: The authors declare no conflicts of interest.

Background/objectives: To assess systemic associations of angioid streaks (AS) using a large US healthcare database., Subjects/methods: A retrospective cross-sectional study was conducted of patients diagnosed with AS in a large, national US insurer from 2000-2019. Cases were matched 1:5 to controls. The prevalence rates of established associated disease states and other systemic diseases were calculated and compared using logistic regression. Additionally, the rate of anti-VEGF treatment was assessed as a proxy for the incidence of choroidal neovascularization (CNV)., Results: One thousand eight hundred fifty-two cases of AS and 9028 matched controls were included. The rates of association between AS and the well-characterized conditions included: Pseudoxanthoma elasticum (PXE)-228 patients (12.3%), Ehlers-Danlos syndrome-18 patients (1.0%), Paget's disease-6 patients (0.3%), hemoglobinopathies-30 patients (1.6%), and idiopathic-1573 patients (84.9%). There was a statistically higher prevalence of the following less classically associated diseases among patients with AS compared to controls: hereditary spherocytosis (1.7% vs. 0.6%, p < 0.001), connective tissue disease (1.0% vs 0.3%, p < 0.001) and non-exudative age-related macular degeneration (33.9% vs 10.6%, p < 0.001). Among 1442 eligible cases analyzed, 427 (29.6%) received at least 1 anti-VEGF injection with 338 (23.4%) patients having the injection after their AS diagnosis., Conclusions: In the largest collection of AS patients to date, the classical teaching of systemic disease associations occur at rates far, far lower than previously reported. The association of AS with other less reported diseases highlights new potential associations and may contribute to the understanding of AS formation., (© 2022. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objective: To estimate the incidence and risk factors of visual impairment and complications in eyes with macular neovascularization (MNV) because of angioid streaks (ASs)., Design: Longitudinal multicenter retrospective cohort study., Subjects: Patients with AS-associated MNV treated with anti-VEGF agents and a follow-up of > 3 months., Methods: Clinical and MNV characteristics were collected at baseline. Visual acuity (VA) values and the presence of atrophy or fibrosis were collected at each visit., Main Outcome Measures: Rate of VA change over time and associated factors; the incidence rate of moderate-to-severe visual impairment (MSVI) and blindness and hazard ratio (HR) of candidate risk factors for MSVI; the incidence rate of fibrosis and macular atrophy., Results: Overall, 84 eyes of 66 patients (39 men, 58%) with a mean (standard deviation) age of 55.7 (13.8) years were followed for a mean (standard deviation) of 67.7 (48.5) months. The median number of anti-VEGF doses per eye was 13. The average rate (95% confidence interval [CI]) of visual loss was +0.04 (0.02-0.06) logarithm of the minimum angle of resolution/year (P < 0.001); the visual loss was faster in nonnaive eyes (P = 0.007) and those with better baseline VA (P < 0.001); it was slower in eyes with pattern dystrophy-like features (P = 0.04). The incidence rates (95% CI) of MSVI and blindness were 10.4 (6.88-15)/100-eye-years and 2.33 (1.12-4.29)/100-eye-years. A higher number of injections (HR [95% CI] = 0.45 [0.19-0.94] for receiving ≥ 13 injections vs. < 13; P = 0.03) was protective against MSVI. The incidence rates (95% CI) of fibrosis and macular atrophy were 24.1 (17.5-32.3)/100-eye-years and 14.3 (10.1-19.6)/100-eye-years., Conclusions: Eyes with MNV-related AS had a high rate of visual impairment and propensity to macular fibrosis and atrophy. A higher number of injections yielded better chances of maintaining good VA, suggesting the need for intensive treatment., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. All rights reserved.)

Background: To report an unusual case of central serous chorioretinopathy in a patient with angioid streaks., Case Presentation: The authors describe a case report of a 26-year old male patient presenting acute scotoma and metamorphopsia in OD. He had been diagnosed with angioid streaks complicated with choroidal neovascularization and referred to us for treatment. The patient presented an ETDRS score of 85 letters (20/20) in OD and in OS. The anterior segment examination was unremarkable. Fundoscopy revealed bilateral angioid streaks (AS) and peau d'orange, as well as a small neurosensory retinal detachment in the macula of OD. A multimodal retinal analysis, including fundus photography, infra-red and fundus autofluorescence imaging, spectral-domain optical coherence tomography, optical coherence tomography angiography, fluorescein and indocyanine green angiography was performed. The diagnosis of central serous chorioretinopathy was made in the absence of any identifiable choroidal neovascularization. He was submitted to half-dose photodynamic therapy with verteporfin. One month later, he reported no visual complaints, his vision was 85 letters (20/20) in OD and a complete resolution of the sub-retinal fluid was registered. No signs of choroidal neovascularization were detected on the optical coherence tomography angiography (OCTA). A complete medical workup evaluation was made to exclude systemic diseases usually associated with AS., Conclusions: To the authors' knowledge, this is the second reported case of CSC associated with angioid streaks. The focal abnormalities in the Bruch's membrane and the irregular vascular choriocapillary network associated with AS might predispose to CSC., (© 2022. The Author(s).)

Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder showing phenotypic heterogeneity giving rise to complex comorbidities. The most 'visible' signs are dermatological; however, these may be subtle and hidden from the view of an affected individual. Ophthalmic signs can be easily missed, and here we highlight the importance of a multisystem assessment. We report a patient who developed advanced sight loss due to maculopathy whose underlying PXE aetiology went unnoticed until subtle skin signs were noticed on the lateral aspect of his neck. He was aware of the skin changes. Careful review of his previous retinal imaging showed the presence of 'angioid streaks' and anatomic alteration at the outer retina-Bruch membrane associated with his prior history of choroidal neovascularisation. The diagnosis was subsequently confirmed by skin biopsy and genetic testing. This case highlights the subtlety of both dermatological and ophthalmic signs in PXE.

Objectives: To inspect the inter-reader agreement of different diagnostic modalities in identifying choroidal neovascularization (CNV) activity secondary to angioid streaks (AS) and to analyze the prevalence of subretinal hyper-reflective material (SHRM) in active CNV., Methods: Retrospective study of patients with AS with active CNV; optical coherence tomography (OCT), OCT angiography (OCTA), fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) from each patient were collected. Agreement between two readers using different diagnostic modalities is presented as free-marginal kappa (k) and 95% confidence interval (CI)., Results: This study included 19 eyes of 12 patients with active CNV (5 naive and 14 previously treated). Agreement among readers on CNV activity was excellent for OCT (k =0.88; 95% CI 0.71-1.00), good for FFA (k = 0.70; 95% CI 0.46-0.94) and ICGA (k = 0.58; 95% CI 0.31-0.84), and poor using OCTA (k = 0.39; 95% CI 0.11-0.68). SHRM was the most common OCT finding associated with active CNV (100%); fuzzy borders were present in 53% of SHRM cases at baseline., Conclusions: Identification of CNV activity in AS is challenging; OCT was the best modality to inspect active CNV. The identification of SHRM contributed to recognizing active CNV. Further studies are needed to assess the role of SHRM in anticipating prognosis and guiding treatment of CNV secondary to AS., (© 2021. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: To evaluate the risk of active choroidal neovascularization (CNV) in presence of deep irregular vascular network (IVN) in eyes with angioid streaks (AS)., Methods: Observational case series including three treatment-naive eyes with angioid streaks and IVN, without CNV. Patients were followed-up during 18 months with multimodal imaging including structural optical coherence tomography (OCT) and OCT Angiography (OCT-A) to detect possible neovascular complication., Results: On OCT-A, IVN was detected as a peripapillary and/or macular high-flow lesion, filling the spaces between the angioid streaks in the outer retina slab. Repeated OCT-A could detect an active CNV emerging from the IVN, as a high-flow rich anastomotic vascular network with a perilesional dark halo. Patient was treated with intravitreal injections of Bevacizumab on a Pro Re Nata regimen, with a decreased CNV area and lower vascular density on control OCT-A., Conclusion: OCT-A shown to be helpful in detecting the presence of IVN in asymptomatic eyes with AS during a routine examination. In our series, the IVN seems to be predictor of active CNV, needing a close surveillance and frequent follow-up to allow early treatment upon CNV activation.

Background and Objectives: To investigate the prevalence of areas of dark without pressure (DWOP) and angioid streaks (AS) in patients with sickle cell disease (SCD)., Patients and Methods: This was a consecutive series of 77 adults with SCD., Results: DWOP appeared as multiple patches in 35 of the affected eyes and as a single lesion in 3 eyes. OCT finding demonstrated the ellipsoid layer was hyporeflective in DWOP. AS were identified in six cases (3.9%) and were bilateral in five cases. The prevalence of AS was higher with increasing age, being 67% in the patients older than age 45 years., Conclusion: The prevalence of DWOP in adults with SCD is 25% in this study, which is higher than previously reported, and the prevalence of AS is around 4%, which is midway between prior estimates. Recognition of the clinical examination and imaging features of DWOP reduce the need for additional investigation. [ Ophthalmic Surg Lasers Imaging Retina . 2021;52:620-622.] .

Background: This article is a case report of pseudoxanthoma elasticum (PXE) which was diagnosed based on significant angioid streaks (AS) with choroidal neovascularization (CNV) and regain normal visual function by intravitreal injection with Conbercept., Case Presentation: A 51-year-old woman was referred to the Ophthalmology Department of Qingdao Municipal Hospital (Qingdao, China) on September 14, 2020 for metamorphopsia and loss of vision in the left eye in the preceding three days. Past history: high myopia for more than 30 years, best corrected visual acuity (BCVA) of both eyes was 1.0 (5 m Standard Logarithm Visual Acuity chart in decimal notations), hypertension for six years, and cerebral infarction two years ago, no history of ocular trauma or surgeries or similar patients in family was documented. We used methods for observation, including fundus examination, optical coherence tomography (OCT), fluorescein angiography combined with indocyanine green angiography (FFA + ICGA). Due to her symptoms and manifestations, along with the appearance of her neck skin, which resembled 'chicken skin', we speculated that she should be further examined at the Department of Dermatology by tissue paraffin section and molecular pathology analyses, and the diagnosis of PXE was then confirmed. After intravitreal injection with Conbercept (10 mg/ml, 0.2 ml, Chengdu Kanghong Biotechnologies Co., Ltd.; Chengdu, Sichuan, China) she regained her BCVA., Conclusions: This patient regained her best corrected visual acuity through intravitreal injection with Conbercept. To the best of our knowledge, no publications are available on cases in which a vision loss and the normal visual function can be reverted by intravitreal injection with Conbercept. Although PXE is a disease with low incidence and thus no effective cure established, targeted symptomatic treatment can effectively retard the disease progression and improve visual function, such as intravitreal injection with Conbercept., (© 2021. The Author(s).)

This study aimed to characterize Korean patients with pseudoxanthoma elasticum (PXE) presenting with angioid streaks. Retinal phenotypes were longitudinally evaluated by multimodal ophthalmic imaging, and targeted gene panel sequencing for inherited retinal diseases was conducted. Seven subjects from unrelated families (median age, 51.2 years) were enrolled and followed for a median of 3.2 years. Four asymptomatic patients were significantly younger than three symptomatic patients with decreased visual acuity at presentation (mean age; 38.1 vs. 61.5 years, p = 0.020). The asymptomatic patients maintained good vision (20/32 or better) and had no choroidal neovascularization (CNV) over the observation period. The symptomatic patients showed additional reduction in visual acuity and bilateral CNV occurrence during the longitudinal follow-up. Pathogenic ABCC6 variants were identified in all patients, leading to a diagnosis of PXE. Heterozygous monoallelic variants were identified in four patients and compound heterozygous variants were detected in three patients. Nine ABCC6 variants were identified, including one novel variant, c.2035G>T [p.Glu679Ter]. This is the first genetic study of Korean patients with PXE.

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Purpose: To demonstrate how a patient with recurrent episodes of choroidal neovascularization (CNV), secondary to angioid streaks, can be managed successfully with a pro re nata regime of intravitreal bevacizumab injection over an eight-year period., Method: A 32-year-old white woman with pseudoxanthoma elasticum has been followed up over an eight-year period for management of recurrent episodes of CNV in both eyes. She was educated to recognize the early signs and symptoms of CNV. Physical examination including visual acuity and slit-lamp examination as well as investigations such as macula optical coherence tomography and optical coherence tomography angiography were performed. Bevacizumab injections were given to her when she was diagnosed with CNV., Results: Multiple episodes of CNV were successfully treated with pro re nata regimes of intravitreal bevacizumab injections. The patient was able to maintain excellent visual acuity of 0 logarithm of the minimum angle of resolution even after suffering recurrent episodes of CNV., Conclusion: This case report supports that a pro re nata regime of intravitreal bevacizumab injection therapy can be used successfully to treat recurrent episodes of CNV in a patient with pseudoxanthoma elasticum over an eight-year period. Early diagnosis through patient education and the use of appropriate diagnostic tools such as optical coherence tomography angiography have enabled us to deliver early treatment, resulting in an excellent outcome for this patient.

Purpose: To describe a case of focal choroidal excavation (FCE) complicated with Type-2 choroidal neovascularization (CNV) in a patient with angioid streaks secondary to pseudoxanthoma elasticum before and after treatment with bevacizumab., Methods: Fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography (SD-OCT) and SD-OCT angiography were performed in a 60-year-old white woman with angioid streaks and bilateral FCE. Spectral domain OCT images were taken before and after three-monthly intravitreal injections of bevacizumab. Histopathological analysis of the dermis established the diagnosis of pseudoxanthoma elasticum., Results: Multimodal imaging revealed bilateral FCE and CNV. Spectral domain OCT diagnosed bilateral FCE and Type-1 and Type-2 CNV in the right eye, and irregular vascular network, along macular streak, in both eyes, which were not observed on fluorescein neither on indocyanine green angiography, but only on SD-OCT angiography. Patient presented good anatomical and functional response to intravitreal injections of bevacizumab., Conclusion: Focal choroidal excavation is a rare condition detected mainly by SD-OCT, which may be associated with angioid streaks secondary to pseudoxanthoma elasticum and complicated by CNV. Multimodal imaging is important for diagnosis and follow-up of such patients, even in the absence of signs of CNV, and anatomical and functional response to anti-vascular endothelial growth factor therapy is good.

Background: Sleep apnea syndrome (OSAS) has been associated with different ocular manifestations including glaucoma, floppy eye syndrome, punctate keratitis, keratoconus, and optic neuropathy. Angioid streaks are mainly associated with pseudoxanthoma elasticum (PXE) although they can appear in other systemic conditions affecting the elastic fibers., Methods: This is a prospective, cross-sectional study. A complete ophthalmic examination was performed in 92 patients undergoing overnight polysomnography for suspicion of OSAS. Diagnosis and classification of OSAS were made based on apnea-hypopnea index (AHI). Stereoscopic optic disc photographs were taken in all patients and independently evaluated by two ophthalmologists. Patients with angioid streaks were referred to a dermatologist for axillary skin biopsy in order to rule out pseudoxanthoma elasticum or other skin abnormalities., Results: Bilateral angioid streaks were observed in three patients who had been diagnosed with severe OSAS (AHI > 30/h). No clinical features characteristic of pseudoxanthoma elasticum or other pathological skin signs were observed. Skin biopsies were normal for all three patients, supporting the diagnosis of idiopathic angioid streaks. One of the patients developed bilateral choroidal neovascularization secondary to the angioid streaks over subsequent years., Conclusions: In view of the low prevalence of idiopathic angioid streaks in the general population, the finding of angioid streaks in patients with severe OSAS suggests OSAS as a possible risk factor for its development. The hypothesis of a connective tissue abnormality that could explain an association between both entities deserves further elucidation.

Significance: Alagille syndrome is rare genetic disease, which affects liver and heart function. Cases are frequently diagnosed late, and a complete ocular examination aids in the diagnosis. Although ophthalmic manifestations are usually benign, occasionally, sight-threatening complications occur., Purpose: The case presented herein highlights a rare condition, which usually can be diagnosed by the ophthalmological findings. However, in this particular case report, the complication of angioid streaks and choroidal neovascularization is reported for the first time in Alagille syndrome., Case Report: Α 32-year-old woman diagnosed with Alagille syndrome presented with diminution of vision in the left eye. The cause was choroidal neovascularization related to angioid streaks. She was treated with intravitreal injections of ranibizumab but developed an extensive macular scar. A few years later, she developed the same complication in the right eye and was treated similarly., Conclusions: Alagille syndrome has many ophthalmic manifestations, most of them benign with minimal threat to vision. Herein for the first time, we present a case of Alagille syndrome with angioid streak-related choroidal neovascularization, which resulted in severe vision loss., Competing Interests: Conflict of Interest Disclosure: None of the authors have reported a financial conflict of interest., (Copyright © 2021 American Academy of Optometry.)

Purpose: To study the appearance of angioid streaks (AS) in swept source optical coherence tomography angiography., Methods: Retrospective observational study of 16 patients (31 eyes) with various stages of AS. All included patients underwent complete ophthalmologic examinations including best-corrected visual acuity (BCVA), slit-lamp examination, indirect ophthalmoscopy and fundus photography. Swept source optical coherence tomography (SS-OCT), OCT angiography (OCT-A) and fluorescein angiography were also performed., Results: En face OCT detected hyper-reflective points in 65% of cases, with a choriocapillaris (CC) shadow on the corresponding OCT-A. Diffuse CC rarefaction was detected in 94%. In eyes without neovascular complications, streaks were visible as a hyposignal in the outer retina. An irregular vascular network (IVN) was detected in 80% of eyes. It filled the spaces between the AS and corresponded to flat elevation of the retinal pigmentary epithelium. Twenty-four eyes had choroidal neovascularization (CNV). CNV was type 1 in 8%, type 2 in 43%, mixed in 20% and unclassified in 29% because of a large scar. We found multiple sites of CNV in 8% of cases. CNV shape was tangled in 66% and in 2 eyes with newly diagnosed CNV. OCT-A showed a perilesional halo around new CNV. The morphology and configuration of neovascular network follow the IVN and the path of the AS and arises in proximity to sites of BM disruption., Conclusion: OCT-A allows early detection and monitoring of AS and their neovascular complications. It shows CC rarefaction, IVN and a predominantly tangled shape of CNV. However, there are some limitations associated with difficulty in characterizing signs of CNV activity., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: To investigate whether the extent of Bruch's membrane calcification is associated with choroidal neovascularization (CNV) and macular atrophy in patients with pseudoxanthoma elasticum (PXE) by using the extent of angioid streaks as a surrogate marker for the degree of Bruch's membrane calcification., Design: Retrospective cross-sectional study., Methods: We investigated 301 patients with PXE (median age, 52 years; range, 9-79 years) in a tertiary referral center. For both eyes, we graded the extent of angioid streaks, that is, their distance from the optic disc, into 5 groups. Imaging was systematically assessed for signs of CNV and macular atrophy. Associations between the extent of angioid streaks and CNV or macular atrophy were investigated using regression analysis., Results: CNV was present in 148 patients (49%) and retinal atrophy in 71 patients (24%). The extent of angioid streaks was associated with older age (P for trend = 1.92 × 10 -15 ) and a higher prevalence of CNV and/or macular atrophy (P for trend = 4.22 × 10 -10 and P for trend = 5.17 × 10 -6 , respectively). In addition, the extent of angioid streaks was associated with the presence of CNV when adjusted for age and sex (odds ratio, 1.9; 95% confidence interval, 1.3-2.9) and with more severe macular atrophy (proportional odds ratio, 2.3; 95% confidence interval, 1.5-3.6)., Conclusions: In patients with PXE, longer angioid streaks are associated with an increased risk of CNV and macular atrophy, even after adjustment for age. These findings are relevant when counseling PXE patients on their visual prognosis., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe patients with late-onset pseudoxanthoma elasticum (PXE) associated with a likely hypomorphic ABCC6 variant., Design: Retrospective observational case series., Methods: Clinical evaluation, multimodal retinal imaging, genetic testing, and molecular modeling., Results: Three patients, in whom vision symptoms first arose at 80 years of age or later, showed age-related macular degeneration (AMD)-like fundus changes. However, features characteristic of PXE, including discrete angioid streaks and reduced fluorescence on late-phase indocyanine green angiography, prompted genetic testing which revealed the c.1171A>G variant in combination with a large deletion in the ABCC6 gene in each case. None of the patients had obvious skin changes or cardiovascular disease atypical for their age. Comparative molecular modeling supported the hypothesis that the c.1171A>G ABCC6 variant acted as a hypomorphic variant., Conclusions: Late-onset PXE extends the spectrum of ectopic calcification disorders caused by mutations in ABCC6 and may clinically be limited to the eye, mimicking AMD. Patients may be identified based on specific ocular changes, whereas skin and cardiovascular changes may remain ambiguous. The study provides evidence for a role for hypomorphic ABCC6 variants in the pathogenesis of PXE., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: To investigate factors contributing to the visual prognosis of choroidal neovascularization (CNV) secondary to angioid streaks (AS) in a long-term follow-up (> 5 years) study., Methods: Twenty-one patients (32 eyes) affected by CNV secondary to AS were enrolled retrospectively and divided into three groups according to the period of CNV recurrence from the final treatment: group A, no recurrence for more than 12 months; group B, no recurrence for 6-12 months; and group C, no recurrence for < 6 months or ongoing. According to the above classification, we assessed best-corrected visual acuity (BCVA), peau d'orange area, the number of photodynamic treatments and/or intravitreal antiangiogenic drug injections, central choroidal thickness (CCT) and central retinal thickness (CRT) using optical coherence tomography, and enlargement of retinal pigment epithelium (RPE) atrophy., Results: The median follow-up time was 91 months. The median logarithm of the minimum angle of resolution BCVA significantly deteriorated from 0 at baseline to 1 at final follow-up (p < 0.05). Especially, final BCVA in group A showed worst visual outcome despite lowest number of treatments. Peau d'orange areas at baseline were found in 32 eyes (100%). There were no significant differences between initial CRT and final CRT. Median CCT was significantly reduced from 188 μm at baseline to 96 μm at final follow-up (p < 0.05). The median number of treatments was 3.5. Enlargement of RPE atrophy at baseline was found in 31 eyes (96.8%)., Conclusions: Despite the regression of CNV secondary to AS following treatment, the visual prognosis was poor due to the presence of peau d'orange areas, choroidal thinning, and increased RPE atrophy.

Purpose: To report multimodal imaging in a novel case of angioid streaks in a patient with Turner syndrome with 10-year follow-up., Methods: Case report of a patient with Turner syndrome and angioid streaks followed at Bellevue Hospital Eye Clinic from 2007 to 2017. Fundus photography, fluorescein angiography, and optical coherence tomography angiography were obtained., Results: Angioid streaks with choroidal neovascularization were noted in this patient with Turner syndrome without other systemic conditions previously correlated with angioid streaks., Conclusion: We report a case of angioid streaks with choroidal neovascularization in a patient with Turner syndrome. We demonstrate that angioid streaks, previously associated with pseudoxanthoma elasticum, Ehlers-Danlos syndrome, Paget disease of bone, and hemoglobinopathies, may also be associated with Turner syndrome, and may continue to develop choroidal neovascularization, suggesting the need for careful ophthalmic examination in these patients.

Aims: To assess hyperreflective foci (HF) number in angioid streaks (AS) by means of spectral-domain optical coherence tomography (SD-OCT)., Methods: Observational and cross-sectional study. Sixty-two eyes with AS and 62 controls underwent best-corrected visual acuity (BCVA), fundoscopy, and SD-OCT. HF were assessed on the horizontal scan of a six-line radial OCT, in the fovea (1500-μm diameter) and parafovea (500 μm external to the fovea), and sub-classified as retinal or choroidal, small or large. Eyes were distributed in one of four groups, as carrying foveal AS without choroidal neovascularization (CNV) (14 eyes), extra-foveal AS without CNV (14), active CNV (20), and inactive CNV (14). Primary outcome was HF assessment in AS. Secondary outcomes included their correlations with BCVA., Results: AS-affected eyes had higher HF numbers. Our sub-analysis revealed that patients with active CNV had a larger number of retinal and choroidal HF than all the other groups, whereas retinal and choroidal foci were significantly increased in inactive CNV only with respect to controls. Interestingly, patients with foveal AS showed HF number increase in the choroid and fovea. BCVA deterioration positively correlated with the total HF number found in the fovea and the choroid., Conclusion: HF are significantly increased in patients with AS. Despite being especially evident in active CNV, the increasing number in eyes without CNV might suggest new pathogenetic aspects of the disease.

Purpose: To investigate retinal sensitivity in eyes with angioid streaks (AS)., Methods: This study was a retrospective observational case series. A total of 13 eyes from 9 patients with AS underwent ophthalmologic examination, including fundus autofluorescence (FAF), spectral domain optical tomography (SD-OCT), and microperimetry. Retinal pigment epithelium (RPE) atrophy was assessed using FAF. Outer retinal atrophy, more specifically, disruption of the ellipsoid zone, was evaluated using SD-OCT images. The association between retinal sensitivity, RPE atrophy or outer retinal atrophy, and patient demographic characteristics or ophthalmologic findings were investigated., Results: The mean area of outer retinal atrophy was 14.5 ± 12.9 mm 2 , significantly larger than the mean area of RPE atrophy (9.0 ± 9.0 mm 2 ; P = 0.0028). The average retinal sensitivity in the area of RPE atrophy was 2.4 ± 5.6 dB, that in the area of outer retinal atrophy outside RPE atrophy was 14.6 ± 7.5 dB, and that in the area without any atrophy was 25.6 ± 5.1 dB. Reticular pseudodrusen (RPD) was observed in 5 eyes. Eyes with RPD showed a greater extent of both outer retinal atrophy and RPE atrophy than those without RPD and a greater decrease in mean retinal sensitivity., Conclusions: In eyes with AS, especially in those with RPD, large areas of outer retinal atrophy and RPE atrophy were observed, and the retinal sensitivity in the areas was correspondingly decreased.

Angioid streaks are defined as the special morphological alteration of the fundus; the most common clinical manifestations are irregular, reddish brownish stripes around the optic nerve head or on the posterior pole. On the basis of histological examination, the cause of this phenomenon is the breaks and continuity deficiencies in the thin layer of Bruch membrane caused by the degeneration of elastic fibers. The aim of this study is to present the ocular complication of this rare entity through the description of three cases, and to draw attention to systemic diseases in the background. In our first and third cases, pseudoxanthoma elasticum (Grönblad-Strandberg syndrome) was in the background, while in our second case, hematological disease was confirmed. In our first and second cases, the ocular complication was the choroidal neovascularization, which we treated with intravitreal anti-VEGF injection. In our third case, the choroidal rupture was the ocular complication, caused by trauma. Angioid streaks on the fundus may be sub-phenomena of systemic diseases, the detection, differential diagnosis and treatment require interdisciplinary collaboration between associate physicians. Orv Hetil. 2019; 160(25): 994-1000.

Competing Interests: Competing interests: None declared.

Purpose: To stratify the literature on angioid streaks, from pathophysiology to treatment., Methods: Review of the current literature., Results: Angioid streaks are crack-like dehiscences of Bruch membrane, which may coexist with systemic diseases, such as pseudoxanthoma elasticum, Paget disease, Ehlers-Danlos syndrome, hemoglobinopathies, or other diseases of the collagen. Various diagnostic methods, including infrared and red-free retinography, autofluorescence, optical coherence tomography, fluorescein angiography, and indocyanine green angiography, are useful to diagnose, evaluate, and monitor angioid streaks. Choroidal neovascularization consists of a major complication of angioid streaks leading to visual impairment. Therefore, observation could not be a treatment option. Photodynamic treatment or anti-vascular endothelial growth factor agents have been used for the treatment of angioid streaks, offering promising but short-term results. Currently, the available treatment may limit the disease, but not permanently inactivate it., Conclusion: This review discusses the epidemiology, pathophysiology, diagnosis, and treatment of angioid streaks, presenting the existing literature on this topic.

The authors report a case of unilateral curvilinear streaks occurring in a patient with pseudoxanthoma elasticum. These represent a previously unreported finding in this disease, as usually found in inflammatory or infective conditions. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e292-e295.]., (Copyright 2018, SLACK Incorporated.)

Purpose: To analyze the optical coherence tomography angiography features of eyes affected with angioid streaks (AS) and to evaluate their ability to predict choroidal neovascularization (CNV) activity., Methods: Angioid streaks were individuated from a pool of consecutive patients. Eyes with and without CNV were evaluated by multimodal imaging., Results: Thirty-eight eyes of 19 consecutive patients diagnosed with AS were included. Thirty of 38 eyes with CNV and 8 of 38 eyes without CNV were included. In the majority of cases, CNV showed on optical coherence tomography angiography tangled appearance always associated with signs of neovascular inactivity on multimodal imaging (100%-0%, inactive-active, respectively). Choroidal neovascularization cases showing interlacing appearance were often associated with signs of neovascular activity on multimodal imaging (71.4%-28.6%, active-inactive, respectively). Optical coherence tomography angiography revealed a total of 27 AS, of which 20 appeared as a choriocapillary rarefaction, and in 7 AS, optical coherence tomography angiography choriocapillary segmentation revealed an irregular vascular network, possibly representing fibrovascular tissue over the crack-like breaks in Bruch membrane., Conclusion: Optical coherence tomography angiography is a noninvasive tool to detect the presence of CNV secondary to AS and to evaluate CNV activity. Optical coherence tomography angiography is able to add a novel element to the multimodal imaging characterization of AS.

The aim of the current study is to investigate corneal biomechanical properties in detail using Ocular Response Analyzer (ORA) and Corvis ST (CST) tonometry and to analyze the association between corneal biomechanical properties and the frequency of intravitreal anti-vascular endothelial growth factor (VEGF) injections (F IV ) in AS eyes with choroidal neovascularization (CNV). Twenty-eight eyes of 15 patients with AS were enrolled. Mean age of AS patients was 67.9 ± 9.8 years. ORA and CST measurements were carried out, in addition to comprehensive ophthalmic examinations. LogMAR visual acuity (VA) and ΔVA (the change of VA from baseline to the final visit) were calculated in each eye. Also, the relationships between F IV , and the variables of initial age at the observation period, axial length, and corneal biomechanical properties were investigated in eyes with AS using linear mixed model with model selection using AICc. In 28 AS eyes, 16 eyes underwent intravitreal anti-VEGF injections during follow-up period. Lower corneal hysteresis (CH), higher corneal resistant factor (CRF) and higher CST measured the DA ratio were associated with the increase of F IV in AS eyes (p = 0.01, p = 0.002, p = 0.027, respectively), suggesting the usefulness for monitoring of corneal biomechanical properties.

PurposeTo describe optical coherence tomography (OCT) features in the Bruch's membrane (BM) of eyes with angioid streaks (AS) and evaluate their evolution over the follow-up.Patients and methodsPatients with AS presenting between March 2016 and September 2016 at two tertiary referral centers were consecutively recruited in this study. Eligibility criteria included prior spectral domain (SD)-OCT images, taken at least 3 months before at the same referral center, with automated eye tracking and image alignment modules. Alterations of BM were described and compared to previous scans over the follow-up. Multimodal imaging was used to identify alteration of retinal pigment epithelium (RPE) and choroid.ResultsThirty-two eyes of 16 consecutive patients with AS were included. BM undulations, mostly observed around the optic nerve head, were found in 19 (59.4%) of 32 eyes. BM breaks were found in 31 (96.9%) out of 32 eyes. Evolution of BM undulations into BM breaks was observed in 5 eyes (15.6%). Choroidal neovascularization (CNV) was observed in 12 eyes (37.5%) during follow-up, typically in areas of BM interruption.ConclusionsBM undulations, probably caused by high stretching forces exerted on the BM around the optic nerve head, seem to precede some BM breaks. BM interruptions may be a preferred way for the growth of CNV, which was identified in one-third of our cases.

Background: To report the case of a patient with pseudoxanthoma elasticum (PXE) and proliferative diabetic retinopathy (PDR), and discuss the relationship between PXE and diabetic retinopathy (DR)., Case Presentation: A 47-year-old man with PXE presented with angioid streaks and DR in both eyes, and bilateral panretinal photocoagulation was performed for treatment. Vitrectomy had previously been performed in his right eye for vitreous hemorrhage due to PDR. Systemic findings included multiple, discrete, symmetrical, small yellow papules bilaterally in the axilla and inguinal region. Examination on presentation showed vitreous hemorrhage in his left eye, and vitrectomy was performed for treatment. Intraoperative findings showed fibrovascular membrane around the optic disc and vascular arcade. A mottled fundus (peau d'orange appearance) associated with angioid streaks was also present, yet there was no evident choroidal neovascularization (CNV). The postoperative course was satisfactory, and corrected visual acuity improved from 0.02 to 0.7 diopters., Conclusion: Despite the peau d'orange appearance in both eyes of this case, no CNV was evident. The vitreous hemorrhage was thus attributed to PDR. Moreover, we reviewed the published literature and discuss the relationship between PXE and DR.

Purpose: To present a case of nonexudative choroidal neovascularization secondary to angioid streaks in a patient with pseudoxanthoma elasticum. The lesion was monitored over an 8-month period with the use of optical coherence tomography angiography., Methods: Case report., Results: The neovascular tissue area increased by 0.160 mm2 over a period of 8 months without any sign of exudation seen on optical coherence tomography or fluorescein angiography., Conclusions: To our knowledge, this is the first report of a nonexudative choroidal neovascularization secondary to angioid streaks. Given that once a patient with angioid streaks develops choroidal neovascularization in one eye there is a high risk of bilateral involvement within a short amount of time, optical coherence tomography angiography can prove a useful tool for monitoring such lesions over time.

Aagenaes syndrome, also called lymphoedema cholestasis syndrome 1 (LSC1), is characterized by neonatal intrahepatic cholestasis, often lessening and becoming intermittent with age and severe chronic lymphoedema, mainly affecting the lower extremities. The condition is autosomal recessively inherited, and the gene is located on chromosome 15q. The locus, LCS1, was mapped to a 6.6 cM region on chromosome 15. Angioid streaks are visible irregular crack-like dehiscences in bruch's membrane that are associated with atrophic degeneration of the overlying retinal pigment epithelium. Angioid streaks have been described to be associated with pseudoxanthoma elasticum, paget's disease, sickle-cell anaemia, acromegaly, Ehlers-Danlos syndrome, and diabetes mellitus, but also appear in patients without any systemic diseases. Patients with angioid streaks are generally asymptomatic, unless the lesions extend towards the foveola or develop complications such as traumatic bruch's membrane rupture or macular choroidal neovascularization.

Camurati-Engelmann disease (CED) is a rare autosomal dominant disease with various phenotypic expressions. The hallmark of the disease is bilateral symmetric diaphyseal hyperostosis of the long bones with progressive involvement of the metaphysis. Ocular manifestations occur rarely and mainly result from bony overgrowth of the orbit and optic canal stenosis. We report a case of CED showing angioid streaks (ASs) in both fundi with no macular involvement and discuss the possible theories of the pathogenesis of AS in this disease.

Purpose: To characterize angioid streaks (AS) with en face optical coherence tomography (OCT)., Methods: Case report of a patient with myopia presenting with choroidal neovascularization secondary to AS. Swept-source en face OCT ability to image the streaks was compared with spectral-domain and swept-source B-scans as well as color and red-free pictures. A 48-year-old man with myopia presented with sudden central visual loss. Choroidal neovascularization secondary to AS was diagnosed and intraocular anti-vascular endothelial growth factor given with clinical and OCT features improvement., Results: Angioid streaks were visualized as less dark than the overlying retinal and the underlying choroidal vasculature. En face OCT located the changes at the level of Bruch membrane. An AS was found to be interrupted by the choroidal neovascularization, what was not captured by other modalities., Conclusion: En face OCT allows to assess the extent of changes in Bruch membrane and their spatial relationship to choroidal neovascularization.

A 41-year-old male with pseudoxanthoma elasticum who presented with progressive vision loss in his left periphery is discussed. Bilateral angioid streaks, optic disc drusen, choroidal neovascularization, and peau d'orange were present. Imaging of the area with peau d'orange with adaptive optics scanning laser ophthalmoscopy and en face optical coherence tomography at Bruch's membrane (BM) revealed a pattern identical to the patches of peau d'orange visible with conventional fundus imaging techniques. These results show that structural abnormalities at the level of BM, likely a result of calcification, correlate with the characteristic "orange peel" pattern known as peau d'orange. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:436-440.]., (Copyright 2017, SLACK Incorporated.)