title: Ocular manifestations of xeroderma pigmentosum: long-term follow-up highlights the role of DNA repair in protection from sun damage.
abstract: OBJECTIVE
  Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by mutations in DNA repair genes. Clinical manifestations of XP include mild to extreme sensitivity to ultraviolet radiation resulting in inflammation and neoplasia in sun-exposed areas of the skin, mucous membranes, and ocular surfaces. This report describes the ocular manifestations of XP in patients systematically evaluated in the Clinical Center at the National Institutes of Health.
  
  
  METHODS
  Retrospective observational case series.
  
  
  METHODS
  Eighty-seven participants, aged 1.3 to 63.4 years, referred to the National Eye Institute (NEI) for examination from 1964 to 2011. Eighty-three patients had XP, 3 patients had XP/Cockayne syndrome complex, and 1 patient had XP/trichothiodystrophy complex.
  
  
  METHODS
  Complete age- and developmental stage-appropriate ophthalmic examination.
  
  
  METHODS
  Visual acuity; eyelid, ocular surface, and lens pathology; tear film and tear production measures; and cytologic analysis of conjunctival surface swabs.
  
  
  RESULTS
  Of the 87 patients, 91% had at least 1 ocular abnormality. The most common abnormalities were conjunctivitis (51%), corneal neovascularization (44%), dry eye (38%), corneal scarring (26%), ectropion (25%), blepharitis (23%), conjunctival melanosis (20%), and cataracts (14%). Thirteen percent of patients had some degree of visual axis impingement, and 5% of patients had no light perception in 1 or both eyes. Ocular surface cancer or a history of ocular surface cancer was present in 10% of patients. Patients with an acute sunburning skin phenotype were less likely to develop conjunctival melanosis and ectropion but more likely to develop neoplastic ocular surface lesions than nonburning patients. Some patients also showed signs of limbal stem cell deficiency.
  
  
  CONCLUSIONS
  Our longitudinal study reports the ocular status of the largest group of patients with XP systematically examined at 1 facility over an extended period of time. Structural eyelid abnormalities, neoplasms of the ocular surface and eyelids, tear film and tear production abnormalities, ocular surface disease and inflammation, and corneal abnormalities were present in this population. Burning and nonburning patients with XP exhibit different rates of important ophthalmologic findings, including neoplasia. In addition, ophthalmic characteristics can help refine diagnoses in the case of XP complex phenotypes. DNA repair plays a major role in protection of the eye from sunlight-induced damage.
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. brooksb@mail.nih.gov
authors.forename: Brian P
authors.initials: BP
authors.lastname: Brooks
authors.forename: Amy H
authors.initials: AH
authors.lastname: Thompson
authors.forename: Rachel J
authors.initials: RJ
authors.lastname: Bishop
authors.forename: Janine A
authors.initials: JA
authors.lastname: Clayton
authors.forename: Chi-Chao
authors.initials: CC
authors.lastname: Chan
authors.forename: Ekaterini T
authors.initials: ET
authors.lastname: Tsilou
authors.forename: Wadih M
authors.initials: WM
authors.lastname: Zein
authors.forename: Deborah
authors.initials: D
authors.lastname: Tamura
authors.forename: Sikandar G
authors.initials: SG
authors.lastname: Khan
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueda
authors.forename: Jennifer
authors.initials: J
authors.lastname: Boyle
authors.forename: Kyu-Seon
authors.initials: KS
authors.lastname: Oh
authors.forename: Kyoko
authors.initials: K
authors.lastname: Imoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Inui
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Moriwaki
authors.forename: Steffen
authors.initials: S
authors.lastname: Emmert
authors.forename: Nicholas T
authors.initials: NT
authors.lastname: Iliff
authors.forename: Porcia
authors.initials: P
authors.lastname: Bradford
authors.forename: John J
authors.initials: JJ
authors.lastname: Digiovanna
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Kraemer
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003057:Cockayne Syndrome / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair / Q000502:physiology*; D005128:Eye Diseases / Q000175:diagnosis* / Q000209:etiology / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000175:diagnosis* / Q000209:etiology / Q000517:prevention & control; D012189:Retrospective Studies; D013472:Sunlight / Q000009:adverse effects*; D054463:Trichothiodystrophy Syndromes / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D014466:Ultraviolet Rays / Q000009:adverse effects; D014792:Visual Acuity / Q000502:physiology; D014983:Xeroderma Pigmentosum / Q000175:diagnosis* / Q000209:etiology / Q000517:prevention & control; D055815:Young Adult
chemical_list: D004247:DNA