title: The spectrum of ocular alterations in patients with β-thalassemia syndromes suggests a pathology similar to pseudoxanthoma elasticum.
abstract: OBJECTIVE
  To determine the prevalence and spectrum of ocular fundus abnormalities in patients with β-thalassemia and to investigate risk factors for their development.
  
  
  METHODS
  Cross-sectional, observational study.
  
  
  METHODS
  A total of 255 patients with β-thalassemia major (TM) and β-thalassemia intermedia (TI) were consecutively recruited and investigated.
  
  
  METHODS
  Patients underwent best correct visual acuity, indirect ophthalmoscopy, and fundus photography, including fundus autofluorescence (FAF) and near-infrared reflectance imaging using a confocal scanning laser ophthalmoscope (cSLO). Hematologic parameters were determined, including mean ferritin levels, aspartate amino transferase, alanine amino transferase, calcium, pre-transfusion hemoglobin, history of splenectomy, and liver iron concentration. Factors associated with the ocular phenotype were assessed using logistic regression.
  
  
  METHODS
  Ocular phenotype as determined by clinical examination and used multimodal imaging.
  
  
  RESULTS
  A total of 153 patients (60.0%) affected by TM and 102 patients (40.0%) affected by TI participated, of whom 216 (84.7%) were receiving iron-chelating therapy. Ocular fundus abnormalities characteristic of pseudoxanthoma elasticum (PXE) were detected by cSLO in 70 of 255 patients (27.8%) and included peau d'orange (19.6%), angioid streaks (12.9%), pattern dystrophy-like changes (7.5%), and optic disc drusen (2.0%). Pseudoxanthoma elasticum-like changes were more frequent in patients with TI (P<0.001). Patients with PXE-like fundus changes were older than patients without these fundus changes (P<0.001). In both patients with TI and TM, age (P = 0.001) and splenectomy (P = 0.001) had the strongest association with presence of PXE-like fundus changes in multivariate analyses. A total of 43 of 255 patients (16.9%) showed increased retinal vascular tortuosity independently of the PXE-like fundus changes, which was associated with aspartate amino transferase (P = 0.036), hemoglobin (P = 0.008), and ferritin levels (P = 0.005).
  
  
  CONCLUSIONS
  Pseudoxanthoma elasticum-like fundus changes are a frequent finding in patients with β-thalassemia. In TI, these changes increase with duration or severity of the disease. This particular ocular phenotype suggests an ocular pathology similar to PXE. Retinal vascular tortuosity may be an additional disease manifestation independent of the PXE-like syndrome. Patients with long-standing disease requiring iron-chelating treatment and a history of splenectomy need regular ophthalmic checkups because they are at risk of developing PXE-like fundus changes and potentially of subsequent choroidal neovascularization.
authors: Ophthalmological Unit, Department of Clinical Sciences and Community Health, Ca' Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors: Giulio
authors: G
authors: Barteselli
authors: Ophthalmological Unit, Department of Clinical Sciences and Community Health, Ca' Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors: Laura
authors: L
authors: Dell'arti
authors: Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia.
authors: Robert P
authors: RP
authors: Finger
authors: Department of Ophthalmology, University of Bonn, Bonn, Germany.
authors: Peter
authors: P
authors: Charbel Issa
authors: Rare Diseases Center, Department of Clinical Sciences and Community Health, Ca' Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors: Alessia
authors: A
authors: Marcon
authors: Ophthalmological Unit, Department of Clinical Sciences and Community Health, Ca' Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors: Diego
authors: D
authors: Vezzola
authors: Ophthalmological Unit, Department of Clinical Sciences and Community Health, Ca' Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors: Chiara
authors: C
authors: Mapelli
authors: Rare Diseases Center, Department of Clinical Sciences and Community Health, Ca' Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors: Elena
authors: E
authors: Cassinerio
authors: Rare Diseases Center, Department of Clinical Sciences and Community Health, Ca' Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors: Maria D
authors: MD
authors: Cappellini
authors: Rare Diseases Center, Department of Clinical Sciences and Community Health, Ca' Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors: Roberto
authors: R
authors: Ratiglia
authors: Ophthalmological Unit, Department of Clinical Sciences and Community Health, Ca' Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy. Electronic address: francesco.viola@unimi.it.
authors: Francesco
authors: F
authors: Viola
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002118:Calcium / Q000097:blood; D002648:Child; D004396:Coloring Agents; D003430:Cross-Sectional Studies; D005260:Female; D005293:Ferritins / Q000097:blood; D005451:Fluorescein Angiography; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007208:Indocyanine Green; D007502:Iron Chelating Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009887:Ophthalmoscopy; D010641:Phenotype; D015995:Prevalence; D011446:Prospective Studies; D011561:Pseudoxanthoma Elasticum / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D012307:Risk Factors; D014792:Visual Acuity; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy
chemical_list: D004396:Coloring Agents; D006454:Hemoglobins; D007502:Iron Chelating Agents; D005293:Ferritins; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D007208:Indocyanine Green; D002118:Calcium