Angioid Streaks and Pseudoxanthoma Elasticum

Present the diagnosis and therapeutic approach in a patient with pseudoxanthoma elasticum and ocular involvement. A 46-year-old patient presented for progressive loss of vision and metamorphopsias in the left eye. The ophthalmological examination showed angioid streaks and secondary choroidal neovascularization. The dermatologist performed an incisional biopsy of a skin area in the right axilla that showed white-yellow, discrete streaks. Histopathological examination confirmed the diagnosis of pseudoxanthoma elasticum. It was decided to start intravitreal injections with aflibercept. Three injections were made in the left eye with subsequent visual acuity improvement. Angioid streaks are a rare retinal condition, and pseudoxanthoma elasticum is the most common association. Other systemic conditions are Ehlers-Danlos syndrome, Paget's disease, and hemoglobinopathies. Definite diagnosis requires skin lesions or calcified elastic fibers on pathological examination and angioid streaks of the retina. Choroidal neovascularization is a frequent complication and leads to vision loss. Intravitreal inhibitors of vascular endothelial growth factor are currently the first line of treatment. Pseudoxanthoma elasticum has numerous systemic manifestations and requires a multidisciplinary team to be monitored and treated.

Editor, Angioid streaks are irregular, greyish lines that surround the optic disc and extend radially outwards. They are associated with different disorders, the most frequent being pseudoxanthoma elasticum or Grönblad−Strandberg syndrome. In a large proportion of cases, they are associated with choroidal neovascularization (CNV). The treatment most frequently employed for CNV is photodynamic therapy (PDT). However, the current use of antiangiogenic agents for CNV secondary to age-related macular degeneration (AMD) opens a new avenue to treatment for patients affected by CNV secondary to other disorders. Texeira et al. (2006) reported a case of CNV-associated angioid streaks treated with bevacizumab with very good results. We report a case of subfoveal CNV-associated angioid streaks treated with intravitreal pegabtanib sodium. A 41-year-old man presented with a sudden decrease in visual acuity (VA) in the left eye. His best corrected VA was 45 letters (ETDRS). In direct ophthalmoscopy, angioid streaks were observed in both eyes and a lesion suspected of being a neovascular membrane was seen in the foveal area of the left eye (LE). Fluorescein angiography (FA) showed an occult CNV in the LE. Optical coherence tomography (OCT) showed evidence of pigment epithelial detachment (PED) and intraretinal oedema (Fig. 1). Treatment was started with intravitreal injections of sodium pegabtanib (Macugen® 0.3 mg/0.5 ml; ) at regular intervals, with 6 weeks between injections. Four injections of pegabtanib were administered. After 36 weeks, BCVA in the LE was 79 letters. No leakage was seen on FA. Examination by OCT showed a dramatic improvement in the PED and complete disappearance of the intraretinal oedema. No systemic or ocular side-effects were reported. Up figures: fluorescein angiography (FA) and optical coherence tomography (OCT) before treatment; Down figures: FA and OCT post treatment. The most frequent cause of vision loss in patients with angioid streaks is CNV, which occurs in 86% of cases. Photodynamic therapy with verteporfin (Visudyne®) had been the most broadly applied treatment for this type of CNV until the new antiangiogenic therapies emerged. Various authors have found differing results with PDT (Arias et al. 2006; Browning et al. 2002; Karacorlu et al. 2002), but some of the series reported were affected by significant limitations (Arias et al. 2006; Browning et al. 2002; Karacorlu et al. 2002). Antiangiogenic agents are a new therapy for AMD and depend on their inhibitory effect on vascular endothelial growth factor (VEGF). Pegabtanib avoids significant visual loss in patients affected with AMD (Chakravarthy et al. 2006). In addition, bevacizumab and ranibizumab have appeared as alternatives. Texeira et al. (2006) reported a case of CNV associated-angioid streaks treated with two injections of bevacizumab (Avastin®), in which a dramatic visual recovery was seen, along with lack of leakage in OCT and FA. The fundamental difference between this case and the one we present concerns the type of CNV. Texeira et al. (2006) described a classical neovascular membrane; by contrast, our case involved a neovascular membrane of the occult type, which is less frequently associated with angioid streaks. Another difference concerns the number of injections: our case required four injections, whereas Texeira et al. (2006) administered two. Best corrected VA at the end of treatment was very good in both cases. Further research is required, involving detailed studies with extended follow-up to determine the efficacy and safety of intravitreal sodium pegabtanib (Macugen®; pfizer) in the treatment of CNV associated with angioid streaks.

The present study reports a case of a patient with choroidal neovascularization (CNV) associated with pseudoxanthoma elasticum (PXE). We observed the functional and anatomical improvement of the patient treated with intravitreal vascular endothelial growth factor (VEGF) inhibitor bevacizumab. The study also systematically searched the database for similar cases to provide a literature review. Data concerning the clinical features, treatment strategies and outcomes were extracted and analyzed. Retrospective interventional case report and systematic literature review. A 56-year-old healthy Chinese woman with CNV secondary to PXE was reported. Examinations included best corrected visual acuity (BCVA), biomicroscopy, optical coherence tomography (OCT), fluorescein and indocyanine green angiography and digital fundus photography. The patient managed with intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections (bevacizumab 1.25 mg/0.05 mL). The Cochrane Library, PubMed, OVID, and UpToDate databases were searched using the term pseudoxanthoma elasticum or Gronblad-Strandberg syndrome with the limits English. Articles that predated the databases were gathered from current references. Fundus examination revealed angioid streaks bilaterally and CNV in left eye (LE). After the patient underwent three intravitreal injections of bevacizumab, the LE showed absorption of the subretinal fluid and shrinkage of the CNV. Visual acuity (VA) was improved in her treated LE. Bevacizumab treatment was well tolerated with no adverse events reported. Approximately ten articles about 45 patients (49 eyes) describing CNV secondary to angioid streaks in PXE treated with anti-VEGF were found in the literature search. In the present case, bevacizumab of an initial three injection loading dose, achieved maintenance of visual function in the treatment of CNV associated with angioid streaks in PXE. Literature articles concluded that the intravitreal application of anti-VEGF is highly efficient for improving and stabilizing the lesion as well as the eyesight. So we believe that anti-VEGF therapy can be a great choice of treatment for CNV secondary to angioid streaks related PXE.

Calcinosis, Paget's disease, and arteriosclerosis are three systemic disturbances in which the etiology and pathogenesis are not well understood. Anything which may contribute to our knowledge of these conditions merits serious consideration. The purpose of this presentation is to report two unusual cases of pseudoxanthoma elasticum associated with systemic manifestations and to arrive at a possible pathogenesis for this process. In the first patient the cutaneous changes were widely generalized, involving all the skin except the scalp, palms, and soles. There was also extensive peripheral vascular disease and widespread calcification of the major blood vessels, as well as extensive calcinosis of the subcutaneous tissues of the lower extremities with gangrene. The second patient had Paget's disease associated with angioid streaks and pseudoxanthoma elasticum. It is now well recognized that pseudoxanthoma elasticum is a cutaneous expression of a generalized disturbance (probably genetic) of some

Retinal autofluorescence imaging in patients with pseudoxanthoma elasticum

Stries angioïdes compliquées de néovaisseaux choroïdiens révélant un pseudoxanthome élastique : diagnostic et stratégie thérapeutique. À propos d’un cas

Pseudoxanthoma elasticum (PXE) is a rare, genetic,multisystem connective tissue disorder primarily affectingthe skin, eyes, and the cardiovascular system (CVS) [1, 2].PXE is characterized by progressive pathologic calcificationand fragmentation of the elastic tissue in the affected organs.PXEappears to bepresent inall overthe world’s populations.In different reports, the prevalence is given to range between1:25,000 and 1:100,000 [3]. Due to lack of adequate knowl-edge among patients and physicians, delay in diagnosis, andgenetic heterogeneity, the exact prevalence of PXE might beunderestimated. Although autosomal recessive inheritancepatterns have mainly been reported, some families show au-tosomal dominant inheritance and some cases are sporadicwithout family history [4]. In most cases, the skin is the firstorgan system affected. Skin changes are usually detected inthe second or third decade [5].Theaffectedskineventuallybecomeslax,redundant,andinelastic.PXEalsoaffectsocularfundusduetopathologicchangesinBruch’smembrane.Earlyocular findings are pigment irregularities of the temporalfundus called “Peau d’ orange”, angioid streaks due to breaksof Bruch’s membrane and later choroidal neovascularisationand disciform scars [1]. CVS manifestations of PXE includearterial hypertension, peripheral arterial disease, anginapectoris, restrictive cardiomyopathy, mitral valve prolapse,and sudden cardiac death [3, 6].A 61-year-old female patient was referred to our derma-tology outpatient clinic by the ophthalmology clinic becauseof angioid streaks detected on fundus examination. Patientdid not have any subjective complaints. She had had historyof diabetes for 11 years and coronary artery disease for10 years. On dermatologic examination, we detected yellowcobblestone like lesions with lax, redundant, and inelasticskin over the anterior and lateral parts of the neck and axilla(Fig. 1). She had not consulted any dermatologist beforebecause of these lesions.Patient had applied to the ophthalmology outpatient clin-ic because of visual impairment. Best corrected visual acu-itieswere0.2/0.2andintraocularpressureswere15/15mmHgrespectively for the right and left eyes. Anterior segmentswere normal. Fundoscopy revealed bilateral angioid streaksoriginating from the optic disk, radiating outwards especiallyunder the macula as grayish–brownish irregular lines (Figs. 2and 3). Optical coherence tomography examination re-vealed increased reflectivity at the level of retinal pig-ment epithelium–Bruch’smembrane–choroid complex.Biopsy taken from the affected skin showed calcifiedand fragmented elastic fibers in the middle and lowerdermis and confirmed the diagnosis.PXE is a rare connective tissue disorder leading to abroad range of complications including mainly the skin,eyes, and CVS [1]. Clinical findings are due to pathologiccalcificationandfragmentation ofelastic tissue inthe dermisof the skin, Bruch’s membrane of the retina, and intima ofthe vascular arteries [5]. These pathologic changes result incharacteristic skin lesions, visual problems, various CVScomplications, and rare problems such as gastrointestinalsystem bleeding [7].Clinical manifestations of PXE are rarely present at birth.The skin is the first organ affected in most cases and the

To analyze the retinal and choroidal vascular abnormalities in eyes with angioid streaks (AS) associated with pseudoxanthoma elasticum (PXE). Color photographs and fluorescein angiograms of 54 eyes of 27 consecutive patients with AS and PXE were examined retrospectively. Four (7%) of the 54 eyes had a major vascular abnormality at the level of the disc; this took the form of a large vascular loop corresponding to an arteriovenous communication between retina and choroid in 3 eyes (6%) and an anastomosis between 2 retinal arteries in 1 eye (2%). Analysis of the vascular network in these eyes showed several vascular abnormalities, among which chorioretinal arteriovenous communications appear to be the most dramatic.

Communications between the ciliary and retinal circulations have been described in association with central retinal artery occlusion,^1,2meningioma of the optic nerve,¹and op-tic disc drusen.³We examined a patient with angioid streaks and pseudoxanthoma elasticum who had a congenital communication between cilioretinal and retinal arteries. <h3>Report of a Case.</h3> A 35-year-old woman was examined for decreased vision in the left eye. Her best-corrected visual acuity was 20/20 OD and 20/200 OS. Results of a slit-lamp examination were normal and intraocular pressures by applanation tonometry were 14 mm Hg bilaterally. Ophthalmoscopy disclosed bilateral angioid streaks with associated peau d'orange pigmentary change. In the right eye, a cilioretinal artery coursing inferior and then temporal to the fovea communicated directly with a superotemporal branch retinal artery (<b>Figure 1</b>). Fluorescein angiography confirmed that angioid streaks were present (<b>Figure 2</b>). It showed retrograde filling of the cilioretinal artery from the superotemporal

Imágenes funduscópicas con autofluorescencia en pacientes con pseudoxantoma elástico

Congenital haemolytic anaemia may be associated with pseudoxanthoma elasticum (PXE)-like clinical manifestations. The cardiovascular system of 14 homozygous and double heterozygous beta-thalassaemia patients with skin and retinal vessel alterations similar to those in genetic PXE was analysed over a period of 12 years and compared with that of 13 relatives (five sets of parents, one single parent, two thalassaemic brothers), and that of the control group composed of 16, age- and sex-matched, thalassaemic patients. All patients with clinical PXE-like skin lesions exhibited, by light and electron microscopy, dermal alterations and mineralization of elastic fibres identical to those typical of inherited PXE. None of the relatives and none of the control group showed clinical or structural findings of PXE. The follow-up started in 1988. After 12 years of clinical observation, six patients showed dramatic progression of skin involvement, angioid streaks had progressed in two subjects. One patient had recurrent gastrointestinal bleeding and underwent partial stomach removal for gastric artery aneurysm, one underwent colon resection for intestinal infarct, one patient had a transitory ischaemic attack, one died after an intracranial haemorrhage, two patients died from cardiovascular disease and one from neoplasia. Thalassaemic patients with PXE-like skin lesions also manifest PXE-like vessel alterations that progress with time. Considering the severe outcome of these lesions, accurate monitoring should be routinely performed on the cardiovascular system of thalassaemic patients with PXE-like skin manifestations.

The blood retinal barrier was investigated in a group of patients with angioid streaks and pseudoxanthoma elasticum, using the technique of vitreous fluorophotometry. Angioid streaks are breaks in the elastic layer of Bruch's membrane with atrophy of the adjacent pigment epithelium. The retinal pigment epithelial cells and their intercellular junctions form part of the blood retinal barrier. In this study, it was found that despite the presence of angioid streaks and extensive areas of pigment epithelial atrophy the blood retinal barrier was intact. In contrast, when disciform degeneration had occurred the blood retinal barrier was abnormal. It is proposed that vitreous fluorophotometry could be used to identify those patients developing disciform degeneration at an early and therefore potentially treatable stage.

Pseudoxanthoma elasticum with abnormal nailfold microcirculatory findings.

Pseudoxanthoma elasticum (PXE) is a hereditary disorder that affects primarily the elastic tissues of skin, eyes and blood vessels. Its estimated prevalence is thought to be 1:25,000 - 100,000. PXE patients also carry an increased risk for cardiovascular and gastrointestinal diseases. Early diagnosis can play a crucial role in preventing early loss of vision and systemic complications in these patients however despite having characteristic clinical features; it is still to a large extent being under-diagnosed. Here we present two cases of PXE with reduced vision.

A case of vision loss in a patient with angioid streaks and pseudoxanthoma elasticum is described. Discussion includes the natural course and clinical appearance of the disease, the role of trauma, and recommended optometric management.