LONG-TERM PROGNOSIS OF CHOROIDAL NEOVASCULARIZATION COMPLICATING 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.

Incidence and Risk Factors of Visual Impairment in Patients with Angioid Streaks and Macular Neovascularization.

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.

HYPERREFLECTIVE FOCI PRECEDE MACULAR NEOVASCULARIZATION FORMATION IN ANGIOID STREAKS.

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.

Central serous chorioretinopathy and angioid streaks: coincidental?

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.

Seeing through the cracks.

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.

IS VAGINAL DELIVERY HARMFUL TO PATIENTS WITH PSEUDOXANTHOMA ELASTICUM?

BACKGROUND/PURPOSE: To investigate the effect of a vaginal delivery (VD) on retinal pathology in patients with pseudoxanthoma elasticum. METHODS: Retrospective case series. All 14 consecutive women with pseudoxanthoma elasticum who visited the ophthalmology department during pregnancy and after delivery between 2010 and 2018 were included. Prepartum and postpartum imaging consisted of color imaging, near-infrared imaging, and optical coherence tomography and was assessed on occurrence of (sub)retinal hemorrhages and change in angioid streaks. RESULTS: Fourteen patients (15 deliveries) were included, of whom 11 patients (79%) had a VD and three patients (21%) a secondary caesarian section. Data of three patients with VD (four deliveries) could not be assessed for (sub)retinal hemorrhage within 10 weeks postpartum. The median age at delivery was 31 years (IQR 29-37). One patient with VD (9%) had a choroidal neovascularization and was treated with anti-VEGF injections before assisted delivery. All patients had angioid streaks in the central 5,500 µ m of the posterior pole of both eyes. After delivery, no patient in the VD or caesarian section group presented with progression of angioid streaks or (sub)retinal hemorrhage. CONCLUSION: Pushing during the expulsion phase of VD seems safe in pseudoxanthoma elasticum patients without active choroidal neovascularization, and the presence of angioid streaks alone should not be an indication for elective caesarian section.

The identification of activity of choroidal neovascularization complicating angioid streaks.

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.

Irregular vascular network identified with OCT-A in angioid streaks: A probable predictor of active choroidal neovascularization (case series).

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.

Contribution of OCT angiography in angioid streaks.

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.

MULTIMODAL IMAGING OF FOCAL CHOROIDAL EXCAVATION COMPLICATED BY CHOROIDAL NEOVASCULARIZATION IN A PATIENT WITH ANGIOID STREAKS AND PSEUDOXANTHOMA ELASTICUM.

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.

PSEUDOXANTHOMA ELASTICUM: SUCCESSFUL LONG-TERM MANAGEMENT OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO ANGIOID STREAKS WITH PRO RE NATA INTRAVITREAL BEVACIZUMAB INJECTIONS.

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.

Intravitreal aflibercept for management of choroidal neovascularization secondary to angioid streaks : The Italian EYLEA-STRIE study.

PURPOSE: To investigate the effect and the safety of intravitreal aflibercept in patients affected by choroidal neovascularization secondary to angioid streaks with a long-term follow-up. METHODS: Multicentre, open-label, phase IIb study (EYLEA-STRIE, EudraCT Number 2014-000986-30) involving four Italian centres (IRCCS Ospedale San Raffaele (Milano), Fondazione G.B. Bietti (Roma), Policlinico (Milano), Ospedale Luigi Sacco (Milano)). Patients with active choroidal neovascularization secondary to angioid streaks with foveal involvement were prospectively enrolled and followed for 18 months. All the patients received intravitreal 2 mg/0.05 mL aflibercept at the time of enrolment, followed by a pro-re-nata regimen for 48 weeks. Best-corrected visual acuity and central macular thickness were measured monthly. Adverse events were monitored at each visit. RESULTS: Twenty-three eyes of 20 patients were analysed. Mean number of injections per patient was 4.30 ± 1.2. At week 48, the best-corrected visual acuity was 0.42 ± 0.40 LogMAR (p = 0.6 from baseline) and 18 eyes (81.8%) featured stability within 15 letters. The central macular thickness significantly reduced (p = 0.03). Eleven ocular non-serious adverse events and two serious adverse events were observed (one case of endophthalmitis and one case of acute gastritis were reported). CONCLUSION: Intravitreal aflibercept represents a valid option for the management of choroidal neovascularization complicating angioid streaks. Further studies with longer follow-up and different therapeutic regimens are warranted to ascertain the best control of the disease.

Clinical characteristics and treatment outcomes of angioid streak associated choroidal neovascular membrane (AS-CNV): a Zambian case series.

This case series illustrates clinical features and treatment outcomes of angioid streak associated CNV (AS-CNV) in 3 consecutive patients. Mean age of patients was 43.2 years with one female patient. Bilateral CNV was present in one patient. Comet-tail lesions were present in all cases. No underlying systemic association was found in any of the patients. All patients were treated with 3 loading doses of anti-VEGF injections (ranibizumab in two and aflibercept was used in one case). Subretinal fluid resolved in all cases with no recurrence of CNV activity at mean follow-up of 10.75 months. AS-CNV in Zambian eyes responds favourably to anti-VEGF injections.

Estrías angioides bilaterales con membranas neovasculares coroideas / Bilateral angioid streaks with choroidal neovascular membranas

No disponible

Long-term results of choroidal neovascularization secondary to angioid streaks.

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.

Switching from ranibizumab to aflibercept in choroidal neovascularization secondary to angioid streaks.

PURPOSE: To evaluate the efficacy of switching from intravitreal ranibizumab to intravitreal aflibercept in choroidal neovascularization secondary to angioid streaks. DESIGN: Multicenter retrospective interventional case series. METHODS: Patients previously treated with intravitreal ranibizumab with at least 12-month follow-up (M12) after switching (M0) to intravitreal aflibercept. Switch to intravitreal aflibercept was decided in cases of refractory or recurrent choroidal neovascularization. Primary endpoint: Change of best-corrected visual acuity using the Early Treatment Diabetic Retinopathy Study letters. Secondary endpoints: Mean change of central macular thickness, absence of intraretinal/subretinal fluid on spectral domain optical coherence tomography and the percentage of eyes with absence of leakage on fluorescein angiography. RESULTS: Fourteen eyes of 13 patients were included. Mean best-corrected visual acuity was 65.0 ± 21.03 letters at M0 and 63.5 ± 17.30 letters at M12 (p = 0.5). Secondary endpoints: Mean central macular thickness was 344 ± 194.65 µm at M0 and 268 ± 79.97 µm at M12 (p = 0.008). Absence of intraretinal/subretinal fluid was observed in 71%. Fluorescein angiography (nine eyes) showed absence of leakage in 77% (seven eyes). CONCLUSION: Switching from intravitreal ranibizumab to intravitreal aflibercept represents a therapeutic option in patients with refractory or recurrent choroidal neovascularization secondary to angioid streaks.