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.

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.

A case report: pseudoxanthoma elasticum diagnosed based on ocular angioid streaks and the curative effect of Conbercept treatment.

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.

Angioid streaks and obstructive sleep apnea syndrome: are they related?

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.

Case Report: Alagille Syndrome Presenting with Angioid Streaks.

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.

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.

Retinal sensitivity in angioid streaks.

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 mm2, significantly larger than the mean area of RPE atrophy (9.0 ± 9.0 mm2; 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: A Comprehensive Review From Pathophysiology to Treatment.

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.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF ANGIOID STREAKS.

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.

A case of pseudoxanthoma elasticum with proliferative diabetic retinopathy.

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.

Long-Term Follow-Up of Choroidal Neovascularization due to Angioid Streaks with pro re nata Intravitreal Anti-VEGF Treatment.

PURPOSE: To evaluate the long-term outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) drugs with a pro re nata (PRN) regimen for the treatment of choroidal neovascularization (CNV) secondary to angioid streaks (AS). METHODS: This is a retrospective, multicenter, noncomparative case series of consecutive AS eyes affected by treatment-naïve CNV. A complete ophthalmologic examination was performed every 30-45 days after the loading phase, including fluorescein angiography and/or optical coherence tomography. RESULTS: In all, 52 eyes of 39 patients were treated with intravitreal bevacizumab and/or ranibizumab and followed up for a mean of 33.8 months. The best corrected visual acuity at baseline was 20/40, and it deteriorated by an average of 6.8 ETDRS letters per year (p < 0.001). We performed an average of 5.1, 6.5, and 6.8 injections at the 1-, 2-, and 3-year follow-up, respectively. CONCLUSIONS: Intravitreal anti-VEGF drugs in a PRN regimen with close monitoring appear to slow the progression of CNV in AS, but they do not prevent the affected eyes from progressive visual loss.

Angioid streaks in aagenaes syndrome.

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.

INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN ANGIOID STREAKS: Four-Year Follow-up.

PURPOSE: To analyze retrospectively the efficacy of intravitreal ranibizumab injections for the management of choroidal neovascularization in patients with angioid streaks over a long term. METHODS: In this "nonrandomized," double-center, retrospective, interventional case series, a consecutive series of patients affected with choroidal neovascularization associated with angioid streaks were treated with intravitreal ranibizumab injections (0.5 mg/0.05 mL). Best-corrected visual acuity, fundus photography, optical coherence tomography, and fluorescein angiography were examined before and after treatment. The primary endpoint was the percentage of eyes with stable or improved visual acuity at the end of follow-up (loss of less than 3 Early Treatment Diabetic Retinopathy Study lines). Secondary endpoints were the percentage of eyes with stable or decreased macular thickness on optical coherence tomography (less than a 10% increase in macular thickness) and the percentage of eyes with persistent leakage on fluorescein angiography at the last observation carried forward. RESULTS: Thirty-five eyes of 27 patients were treated with repeated intravitreal ranibizumab injections (mean of 9.9 ± 7.2 injections, range 2-26) for a mean of 48.6 ± 17.1 months (range 8-66). At the end of follow-up, best-corrected visual acuity was stabilized or improved in 22 of 35 eyes (62.9%). Macular thickness had stabilized or decreased in 16 of 35 eyes (45.7%). At the last follow-up examination, on fluorescein angiography, no further leakage was observed in 27 of 35 eyes (77.1%). CONCLUSION: In this large series of patients with choroidal neovascularization associated with angioid streaks followed for 4 years, ranibizumab injections allowed stabilization of best-corrected visual acuity in most eyes. Ranibizumab appear as an effective therapeutic option in CNV associated with angioid streaks over long time.

Angioid Streaks in Types I and II Congenital Dyserythropoietic Anaemia (CDA).

Background. Angioid streaks (AS) are visible irregular breaks in Bruch's membrane, extending radially from the optic nerve head and with overlaying atrophic retinal pigment epithelium. In 50 % of patients, AS are associated with Pseudoxanthoma elasticum, Ehlers-Danlos syndrome, sickle cell anaemia or Paget's disease. In 50 % of patients, AS are idiopathic. Congenital Dyserythropoietic Anaemia (CDA) is a rare, inherited disorder of ineffective erythropoiesis with morphologically abnormal erythroblasts. CDA was first recognised as a separate entity in 1968 and classified into three main groups. CDA demographics have identified 614 known families and > 700 cases worldwide. A few case reports of AS in CDA I and III have been published, but there is no report of AS in CDA II, the most frequent of the CDAs, as well no follow-up. History and Signs. 8 eyes of 4 CDA patients were examined. The CDA I patients were a 46 year old man and a 52 year old woman. They were first seen in 2009 and followed up for 9 and 11 months, respectively. The 2 female CDA II patients were seen in 2010 and were aged 35 and 42 years at first presentation. Vision, Amsler grid, optical coherence tomography (OCT), fundus pictures and fluorescent angiography were performed. Blood was drawn for neutrophil elastase determination (ELA2). Therapy and Outcome. All patients showed bilateral AS. Mean best corrected visual acuity was 20/20 without metamorphopsia and with normal OCT. During the follow-up period, no progression occurred. No choroidal neovascularisation (CNV) was detected. ELA2 serum levels were normal. Conclusions. This is the first report of AS in CDA II and the first follow-up in CDA I. No evidence of progression was seen within this period of time. Longer follow-up is needed to detect whether AS progresses. All patients with AS should be seen by an ophthalmologist on a regular basis. The risk of CNV is given. Therapy is possible and the outcome is best if the CNV is recognised and treated early.

Peau d'orange and angioid streaks: manifestations of Bruch membrane pathology.

PURPOSE: The aim of this study was to characterize peau d'orange and angioid streaks, characteristic findings in eyes of patients with pseudoxanthoma elasticum, by examining fundus photography and optical coherence tomography imaging. METHODS: Color photographs were evaluated directly as were the component red and green channels. Optical coherence tomography images were evaluated for reflectivity pattern of the band corresponding to the retinal pigment epithelium-Bruch membrane complex. RESULTS: Eighteen eyes of 9 patients with a mean age of 48.7 years (range, 31-61 years) were examined; 7 of them were women. Color photographs showed areas of yellowish opacification that obscured visualization of the underlying choroid. At the outer edges of this confluent area, opacification were nonconfluent changes with similar appearance and these regions were typical peau d'orange. Angioid streaks occurred within and extended up to the outer border of the confluent opacification. Underlying choroidal details could be seen through the regions of peau d'orange and through the gaps in angioid streaks. The red channel image showed increased reflectivity from the confluent deposit and improved visualization of the choroidal vasculature, except where the confluent opacification was located. Optical coherence tomography imaging showed increased reflectivity from the outer border of the retinal pigment epithelium-Bruch membrane complex. CONCLUSION: The findings suggest that the confluent region is the relevant lesion, not the subconfluent zone known as peau d'orange. Imaging characteristics of the confluent area of opacity are consistent with diffuse infiltration with calcium, a chief histologic abnormality of pseudoxanthoma elasticum. The name coquille d'oeuf was suggested for the confluent area of opacity as a consequence.

PERIPAPILLARY ATROPHY WITH LARGE DEHISCENCES IN BRUCH MEMBRANE IN PSEUDOXANTHOMA ELASTICUM.

PURPOSE: To describe a new set of findings in eyes with pseudoxanthoma elasticum, specifically large defects in Bruch membrane. METHODS: Retrospective review of the optical coherence tomography image obtained with the Heidelberg Spectralis of the posterior pole of patients with pseudoxanthoma elasticum. Large dehiscences in Bruch membrane were defined as any defect in Bruch membrane greater than 250 µm in diameter that was not contiguous with a visible angioid streak. RESULTS: There were 28 eyes of 14 patients, with a mean age of 53.6 years; 10 were female. Large dehiscences in Bruch membrane were seen in nine eyes of six patients, and all were within peripapillary atrophy manifested by loss of the choroid and retinal pigment epithelium. The edges of Bruch membrane showed an abrupt termination in the optical coherence tomography images, and often with an upturned edge surrounding the region devoid of Bruch membrane. The mean refractive error of the patients was -2.1 diopters (D) in the right eye and -2.5 D in the left. CONCLUSION: Pseudoxanthoma elasticum shares peripapillary atrophy and large dehiscences of Bruch membrane with pathologic myopia. Although theories of pathologic myopia involve stresses from ocular expansion, those of pseudoxanthoma elasticum typically do not. The Bruch membrane defect in pseudoxanthoma elasticum may be related to fragility secondary to abnormal calcification and to the surrounding abiotrophy of surrounding affected tissues of the posterior pole of the eye.

Pseudoxanthoma elasticum and retinitis pigmentosa in a patient with a novel mutation in the ABCC6 gene.

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.