Mutational spectrum and deep phenotyping in Pseudoxanthoma Elasticum: Findings from a Portuguese cohort.

INTRODUCTION: Pseudoxanthoma Elasticum (PXE) is a rare autosomal recessive disorder originated by disease-causing variants in ABCC6 gene. The purpose of this study was to characterize the genetic landscape, phenotypic spectrum and genotype-phenotype correlations in a Portuguese cohort of PXE patients. METHODS: Multicentric cross-sectional study conducted in patients with a clinical and genetic diagnosis of PXE. Patients were identified using the IRD-PT registry (www.retina.com.pt). Genotypes were classified into 3 groups: (1) two truncating variants, (2) two non-truncating variants, or (3) mixed variants. Deep phenotyping comprised a comprehensive ophthalmologic and systemic evaluation using the updated Phenodex Score (PS). RESULTS: Twenty-seven patients (23 families) were included. Sixteen different ABCC6 variants were identified, 7 of which are novel. The most prevalent variant was the nonsense variant c.3421C > T p.(Arg1141*) with an allele frequency of 18.5%. All patients exhibited ocular manifestations. Cutaneous manifestations were present in most patients (88.9%, n = 24/27). A PS score > E2 was strongly associated with worse visual acuity (B = -29.02; p = 0.001). No association was found between genotypic groups and cutaneous, vascular or cardiac manifestations. CONCLUSIONS: This study describes the genetic spectrum of patients with PXE for the first time in a Portuguese cohort. A total of 16 different variants in ABCC6 were found (7 of which are novel), thus highlighting the genotypic heterogeneity associated with this condition and expanding its mutational spectrum. Still, no major genotype-phenotype associations could be established.

Pseudoxanthoma elasticum-associated angioid streaks near a scleral buckle.

Purpose: We report a patient with pseudoxanthoma elasticum (PXE) with angioid streaks near a scleral buckle site. Observations: A 46-year-old male with PXE presented for evaluation of blurry vision and was found to have classic PXE findings in both eyes and angioid streaks adjacent to the site of a scleral buckle in his left eye. He underwent multimodal imaging, genetic testing, and intravitreal aflibercept in the right eye. Conclusions and importance: Bruch's membrane is known to be fragile in PXE, and patients are often counseled about the heightened risk of playing contact sports. This report raises the question of whether tension from a scleral buckle in the setting of a calcified and brittle BM may increase the likelihood of angioid streaks near the buckle site. In the setting of retinal detachment, it may be worthwhile to carefully weigh the pros and cons of vitrectomy versus buckle for PXE patients.

Angioid Streaks Remain a Challenge in Diagnosis, Management, and Treatment.

Aim: Angioid streaks (ASs) are a rare retinal condition and compromise visual acuity when complicated with choroidal neovascularization (CNV). They represent crack-like dehiscences at the level of the Bruch's membrane. This objective narrative review aims to provide an overview of pathophysiology, current treatment modalities, and future perspectives on this condition. Materials and Methods: A literature search was performed using "PubMed", "Web of Science", "Scopus", "ScienceDirect", "Google Scholar", "medRxiv", and "bioRxiv." Results: ASs may be idiopathic, but they are also associated with systemic conditions, such as pseudoxanthoma elasticum, hereditary hemoglobinopathies, or Paget's disease. Currently, the main treatment is the use of anti-vascular endothelial growth factors (anti-VEGF) to treat secondary CNV, which is the major complication observed in this condition. If CNV is detected and treated promptly, patients with ASs have a good chance of maintaining functional vision. Other treatment modalities have been tried but have shown limited benefit and, therefore, have not managed to be more widely accepted. Conclusion: In summary, although there is no definitive cure yet, the use of anti-VEGF treatment for secondary CNV has provided the opportunity to maintain functional vision in individuals with AS, provided that CNV is detected and treated early.

Macular Neovascularization Secondary to Subclinical Angioid Streaks in Age-Related Macular Degeneration: Treatment Response to Anti-VEGF at 2-Year Follow-up.

INTRODUCTION: To characterize the response to antivascular endothelial growth factor (VEGF) treatment of macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) with subclinical angioid streaks (AS) during a 2-year follow-up. METHODS: Retrospective, longitudinal, case-control, and multicentric study. Among a cohort of neovascular AMD population, we selected patients with subclinical AS and treatment-naïve MNV treated with anti-VEGF for a 2-year follow-up. An age- and sex-matched control group with treatment-naïve MNV secondary to AMD without subclinical AS was selected. Demographics and differences in treatment response (i.e., number of injections needed, anatomical and functional outcomes) between the two groups were analyzed. RESULTS: Among 102 eyes of 102 patients with neovascular AMD, 34 eyes of 34 patients (82 ± 6 years old) were included in the subclinical AS group, whereas 68 eyes of 68 patients (81 ± 6 years old, p = 0.342) in the control group. All eyes with subclinical AS presented RPD compared to 56% of eyes without subclinical AS (p < 0.001). During the 2-year follow-up, eyes with subclinical AS needed more injections (10.6 ± 3.2 vs 8.3 ± 3.1 injections for eyes with and without subclinical AS, respectively, p < 0.001). Visual acuity (VA) decreased during the treatment (from 0.53 ± 0.37 at the baseline to 0.69 ± 0.45 LogMAR at 2-year follow-up, p = 0.044) in eyes with subclinical AS; no VA changes were observed in the control group (p = 0.798). RPE atrophy at the end of the 2-year follow-up affected 74% of cases with subclinical AS and 29% of cases of the control group (p < 0.001). CONCLUSIONS: MNVs secondary to AMD with subclinical AS are characterized by worse functional and anatomical outcomes after 2-year anti-VEGF treatment compared to MNV secondary to AMD without subclinical AS, supporting the different pathophysiological mechanisms involved in this recently described AMD phenotype.

Pseudoxanthoma elasticum veiled as vasculitis: shedding light on an uncommon disorder and an in-depth review of the literature.

Pseudoxanthoma Elasticum (PXE) is a rare genetic disorder caused by an autosomal recessive mutation in the ABCC6 gene. It manifests with distinctive clinical symptoms impacting the skin, eyes, and cardiovascular system, along with an elevated risk of cardiovascular diseases. We present a case of a 34-year-old male patient who was initially referred to the rheumatology clinic for evaluation due to suspected large vessel vasculitis. The patient's primary complaint was severe hemifacial pain radiating to the neck and upper limb. Radiological imaging studies unveiled substantial vascular narrowing and collateral vessel formation, prompting further investigation to exclude systemic vasculitis. Intriguingly, the patient also exhibited cutaneous manifestations, which were later confirmed via skin biopsy as consistent with PXE. An ophthalmological examination further revealed the presence of the classic PXE findings of angioid streaks. Given the rarity of PXE and its multifaceted clinical presentation, it can be particularly challenging to diagnose and manage. As such, cases like the one presented here may necessitate a referral to a rheumatologist for evaluation of potential systemic involvement. To provide a comprehensive perspective on PXE, we conducted a systematic review of case reports published in the past decade in English, collected from PubMed, Scopus, and the Directory of Open Access databases. The analysis of these cases will be discussed to shed light on the diversity of PXE's clinical features and the diagnostic and management dilemmas it poses and to facilitate ongoing exploration and research into this intricate condition, ultimately leading to improved care for individuals affected by PXE.

En-Face Optical Coherence Tomography Is Useful for Assessing Striated Lesions in Angioid Streaks: A Case Report.

Angioid streaks are mainly characterized by radially striated lesions around the optical disc and result in severe vision loss when choroidal neovascularization (CNV) develops at the macula. The prediction of visual prognosis in cases with angioid streaks remains an unsolved problem. In this study, we report the usefulness of en-face optical coherence tomography (OCT) to assess the bilateral striated lesions in angioid streaks. A 59-year-old female who was previously diagnosed with angioid streaks complained of decreased visual acuity in her left eye. However, on en-face OCT, the striated lesions in the right eye with better vision were shown as thicker continuous lesions than those in the left eye. Twenty-four months after the initial visit, her right visual acuity was worse than her left. En-face OCT showed fine-striated lesions extending from those thicker lesions to the macular area in the right eye. The thicker striated lesions observed at the initial visit may be a risk factor for future CNV development and vision loss. The evaluation of lesion size using en-face OCT may be useful for predicting the visual prognosis in angioid streaks.

Subclinical Angioid Streaks with Pseudodrusen: A New Phenotype of Age-Related Macular Degeneration.

INTRODUCTION: To describe subclinical angioid streaks (AS) as a frequent, peculiar age-related macular degeneration (AMD) phenotype, comparing features of eyes with subclinical AS with those of eyes with AMD without AS. METHODS: This was a retrospective, observational study. Among a patient cohort with AMD, we selected patients without known causes for AS whose eyes showed signs of angioid streaks (AS) on structural optical coherence tomography (OCT) but not on fundus examination. Selected OCT features of AS were Bruch's membrane (BM) breaks and large BM dehiscences. RESULTS: Among 543 eyes of 274 patients with AMD (mean ± standard deviation: 82 ± 7 years), 73 eyes of 46 patients (81 ± 7 years; p = 0.432) showed AS features on OCT (OCT AS) that were not visible on fundus examination. Estimated prevalence of subclinical age-related AS was 13.4% (95% confidence interval 10.3-16.3%) in this AMD population. Fifty-three eyes (73%) with AS features were affected by peripapillary atrophy, often with a "petaloid-like" pattern, similar to typical features of AS disease. Almost all cases (97%) presented reticular pseudodrusen (RPD), with (41%) or without (59%) drusen showing a significant difference in RPD prevalence in OCT AS eyes in comparison to AMD eyes without subclinical AS using generalized estimating equations (P < 0.001). Among the 73 subclinical AS cases, 71 were affected by late AMD (57 with macular neovascularization, 14 with geographic atrophy), showing a more advanced AMD stage in comparison with AMD eyes without subclinical AS (P < 0.001). The following OCT features were disclosed: BM breaks in 100% of cases and BM dehiscences in 37%. CONCLUSIONS: Subclinical AS in eyes with AMD is a peculiar phenotype of the disease, with features suggesting a primary involvement of Bruch's membrane and clinical similarities with mild, late-onset pseudoxanthoma elasticum.

Refractory Choroidal Neovascularization in a Patient With Pseudoxanthoma Elasticum and Cowden Syndrome.

Purpose: To describe a patient with concurrent pseudoxanthoma elasticum (PXE) and Cowden syndrome who developed choroidal neovascularization (CNV) secondary to angioid streaks. The CNV presented at a young age and was relatively refractory to intravitreal antivascular endothelial growth factor (anti-VEGF) therapy. Methods: A retrospective chart review was performed. Results: A 32-year-old man was treated for bilateral sequential CNV over 11 years. Good visual acuity was maintained with 53 anti-VEGF injections in the right eye and 82 injections in the left eye. On average, 1 injection was administered every 1.7 months in each eye to control the exudation. A skin biopsy and genetic testing confirmed a diagnosis of PXE. He was also found to harbor a PTEN mutation consistent with Cowden syndrome. Conclusions: The concurrent PTEN mutation lends a possible explanation for the relative resistance of CNV to anti-VEGF therapy in this patient with PXE. Phosphatase and tensin homolog is a tumor suppressor that negatively regulates the VEGF pathway.

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.

Familial Paget's disease of bone with ocular manifestations and a novel TNFRSF11A duplication variant (72dup27).

INTRODUCTION: Paget's disease of bone (PDB) is a skeletal disorder characterized by disorganized bone remodeling due to abnormal osteoclasts. Tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) gene encodes the receptor activator of nuclear factor kappa B (RANK), which has a critical role in osteoclast function. There are five types of rare PDB and related osteolytic disorders due to TNFRSF11A tandem duplication variants so far, including familial expansile osteolysis (84dup18), expansile skeletal hyperphosphatasia (84dup15), early-onset familial PDB (77dup27), juvenile PDB (87dup15), and panostotic expansile bone disease (90dup12). MATERIALS AND METHODS: We reviewed a Japanese family with PDB, and performed whole-genome sequencing to identify a causative variant. RESULTS: This family had bone symptoms, hyperphosphatasia, hearing loss, tooth loss, and ocular manifestations such as angioid streaks or early-onset glaucoma. We identified a novel duplication variant of TNFRSF11A (72dup27). Angioid streaks were recognized in Juvenile Paget's disease due to loss-of-function variants in the gene TNFRSF11B, and thought to be specific for this disease. However, the novel recognition of angioid streaks in our family raised the possibility of occurrence even in bone disorders due to TNFRSF11A duplication variants and the association of RANKL-RANK signal pathway as the pathogenesis. Glaucoma has conversely not been reported in any case of Paget's disease. It is not certain whether glaucoma is coincidental or specific for PDB with 72dup27. CONCLUSION: Our new findings might suggest a broad spectrum of phenotypes in bone disorders with TNFRSF11A duplication variants.

Hypotony Maculopathy Related to Anti-VEGF Intravitreal Injection.

Purpose: To describe a case of hypotony maculopathy following anti-VEGF intravitreal injection (IVI) in a patient with pseudoxanthoma elasticum (PE). Methods: Clinical case report. Results: A 52-year-old male complained of right eye (OD) vision loss 2 days after an uncomplicated anti-VEGF IVI for the treatment of choroidal neovascularization secondary to angioid streaks. Relevant medical history included PE, pathologic myopia, and a previous pars plana vitrectomy (PPV) due to a retinal detachment. OD best-corrected visual acuity (BCVA) dropped from 6/12 to 6/18 after the IVI. Intraocular pressure (IOP) was 3 mmHg and chorioretinal folds were evident in the posterior pole. Topical dexamethasone and atropine were prescribed, and full recovery was noticed after 3 days. Four months later, the patient developed a new episode of vision loss after another IVI. His BCVA was counting fingers, IOP was 2mmHg, and more noticeable chorioretinal folds were found. This time, an open scleral wound at the injection site was evident and a scleral suture was necessary. Once again, the patient recovered well. Conclusion: Hypotony maculopathy following intravitreal injection is a rare condition. However, the described patient presented several conditions which could be related with poor scleral wound closure: intrinsic scleral fragility due to myopia and pseudoxanthoma elasticum; repeated IVI procedures; and absence of vitreous in the posterior segment due to prior vitrectomy. Despite the good outcome, hypotony maculopathy may be a sight-threatening condition, and special attention is necessary for specific patients with risk factors.

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.

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.

Case report: Grönblad-Strandberg syndrome.

Objective: To present a case of secondary type 2 choroidal neovascularization (CNV) and exudative maculopathy in a patient with Grönblad-Strandberg syndrome. Methods: A 37-year-old male was admitted with bilateral progressive painless visual acuity loss and metamorphopsias. A thorough ophthalmologic and clinical examination was performed. Results: Best-corrected visual acuity (BCVA) on presentation was 20/ 200 OD (Oculus Dexter) and 20/ 60 OS (Oculus Sinister). Fundus examination revealed angioid streaks and subretinal hemorrhages on OU (Oculus Uterque), macular fibrosis on OD and "peau d'orange" pigmentary mottling on OS. Leakage areas on fundus fluorescein angiography (FFA) revealed active CNV on OU, which was confirmed by Optical Coherence Tomography (OCT). The presence of typical "plucked chicken" skin lesions in the latero-cervical area and their biopsy confirmed the diagnosis of Pseudoxanthoma elasticum (PXE). Consequently, the diagnosis of Grönblad-Strandberg syndrome was established. Conclusions: Every new diagnosis of angioid streaks entails not only a thorough ophthalmologic evaluation for secondary sight-threatening complications, but also a multidisciplinary evaluation due to the possibility of severe underlying systemic disease. Abbreviations: BM = Bruch's membrane, RPE = Retinal Pigmented Epithelium, PXE = Pseudoxanthoma Elasticum, ABCC6 = ATP binding cassette subtype C number 6, CNV = Choroidal Neovascularization, BCVA = Best-Corrected Visual Acuity, OD = Oculus Dexter, OS = Oculus Sinister, OU = Oculus Uterque, FFA = Fundus Fluorescein Angiography, OCT = Optical Coherence Tomography, IPO = Intraocular Pressure, ECG = Electrocardiogram, anti-VEGF = anti-vascular endothelial growth factor.

A case of angioid streaks that produced choroidal neovascularization after the onset of unilateral acute retinopathy in pseudoxanthoma elasticum.

Purpose: To report a case of angioid streaks that showed non-exudative choroidal neovascularization (CNV) after the onset of acute retinopathy in pseudoxanthoma elasticum (PXE). Observations: A 64-year-old woman with PXE visited our department for an ophthalmologic evaluation. Her decimal best-corrected visual acuity (BCVA) was 1.5, with angioid streaks (AS) around the optic disc in either eye at the first visit. Seven years later, her left eye's BCVA suddenly decreased by 0.3, and the fundus showed blurring of the Ellipsoid zone and vitreous cells along with the retinal pigment streaks on the nasal fovea. Diagnosed as acute retinopathy in PXE, twenty-two weeks after the start of oral prednisolone, the Ellipsoid zone became clear and the BCVA improved to 1.2, but CNV gradually developed. After intravitreal injection of bevacizumab, the CNV was decreased. Conclusions and importance: CNV on the AS lesion may occur after acute retinopathy in PXE.

Bilateral central serous chorioretinopathy in a patient with angioid streaks.

This report describes a case of bilateral central serous chorioretinopathy (CSCR) in a patient with angioid streaks. A 39-year-old male was referred for worsening vision. Best-corrected visual acuity (BCVA) at presentation was 5/10 in his right eye and 4/10 in his left eye. Fundus examination, fluorescein angiography, and optical coherence tomography were compatible with angioid streaks in both eyes associated with macular atrophy due to previous CSCR attack in the right eye and active nonresolving CSCR in the left eye. Macular laser photocoagulation was done in the left eye. After 3 months, subretinal fluid was absorbed and BCVA improved to 7/10. CSCR may occur rarely in patients with angioid streaks and ophthalmologists should consider CSCR in cases with angioid streaks and vision deterioration.

Quantitative Analysis of Choriocapillaris Using Swept-Source Optical Coherence Tomography Angiography in Eyes with Angioid Streaks.

Purpose: to quantitatively analyze choriocapillaris perfusion using swept-source optical coherence tomography angiography (SS-OCTA) in eyes presenting with angioid streaks in comparison with control eyes. Methods: Macular 6 × 6 mm SS-OCTA scans were retrospectively analyzed in eyes with angioid streaks and in control eyes. En face choriocapillaris flow images were compensated with en face choriocapillaris structure images, followed by the Phansalkar local thresholding method (with a window radius of four and eight pixels). Quantitative analysis was performed in the four peripheral 1 × 1 mm corners of the 6 × 6 mm SS-OCTA image to include equidistant and comparable regions. The percentage of flow deficits (FD%), the number and size of the flow deficits (FDs) and the total area of FDs were then calculated. Results: 54 eyes of 31 patients were included in the study: 27 eyes diagnosed with angioid streaks and 27 controls. Analysis of the four 1 × 1 mm peripheral corners of the 6 × 6 mm SS-OCTA image showed that eyes with angioid streaks had a higher FD% compared to the control group (47.62 ± 8.06 versus 38.90 ± 6.38 using a radius of four pixels (p < 0.001); 48.37 ± 7.65 versus 39.66 ± 6.51 using a radius of eight pixels (p < 0.001). The average size of FDs as well as the total area size of the FDs were significantly higher in eyes with angioid streaks compared to control eyes (p < 0.001). Eyes with angioid streaks present reduced choriocapillaris flow compared to control eyes. Decreased choriocapillaris perfusion may contribute, among other factors, to the development of neovascularization and atrophy in patients with angioid streaks.

A Case of Angioid Streaks in Congenital Dyserythropoietic Anaemia Type II.

The authors describe a case report of retinal angioid streaks (AS) in a patient with congenital dyserythropoietic anaemia (CDA) type II and compare the retinal findings to those of an affected first-degree relative without ocular manifestations of the disease. A 52-year-old man with a confirmed diagnosis of CDA type II has been dependent on treatment with regular transfusions and chelating agents. He presents with bilateral retinal AS. The subject's brother, who also has CDA type II, underwent splenectomy in childhood, and has required no treatment since then. He has no ocular manifestations of the disease. To the authors' knowledge, this is only the second time that the presence of retinal AS has been reported in a case of CDA type II. It has been reported more frequently with CDA types I and III. The milder course of disease in the subject's brother likely accounts for the differing retinal findings. The authors explore the pathophysiology of AS in this disease, and the differential diagnosis of chelating agent toxicity. Diagnostic uncertainty around retinal findings can lead to withholding of essential systemic treatment and inappropriate ophthalmological follow-up. It is recommended that all patients with CDA undergo eye examinations.

Clinical practice guidelines for pseudoxanthoma elasticum (2017): Clinical Practice Guidelines for Pseudoxanthoma Elasticum Drafting Committee

Pseudoxanthoma elasticum (PXE) is a progressive hereditary disease that affects tissues such as the skin, retina, blood vessels, and gastrointestinal tracts. Therefore, comprehensive medical care across clinical departments specialized in specific organs is needed to provide the best clinical practices to PXE patients. The Japanese version of clinical guidelines developed by the Japanese Dermatological Association was published in 2017, and aimed to promote equal accessibility of PXE-related medical care. Here, the English version of Japanese guideline is reported, and is intended to be worldwide reference for medical care of PXE.