TY - JOUR
T1 - Ocular manifestations of xeroderma pigmentosum
T2 - Long-term follow-up highlights the role of DNA repair in protection from sun damage
AU - Brooks, Brian P.
AU - Thompson, Amy H.
AU - Bishop, Rachel J.
AU - Clayton, Janine A.
AU - Chan, Chi Chao
AU - Tsilou, Ekaterini T.
AU - Zein, Wadih M.
AU - Tamura, Deborah
AU - Khan, Sikandar G.
AU - Ueda, Takahiro
AU - Boyle, Jennifer
AU - Oh, Kyu Seon
AU - Imoto, Kyoko
AU - Inui, Hiroki
AU - Moriwaki, Shin Ichi
AU - Emmert, Steffen
AU - Iliff, Nicholas T.
AU - Bradford, Porcia
AU - Digiovanna, John J.
AU - Kraemer, Kenneth H.
N1 - Funding Information:
The patients were evaluated under protocols approved by the National Cancer Institute Institutional Review Board, and the research adhered to the tenets of the Declaration of Helsinki. The work is Health Insurance Portability and Accountability Act compliant, and informed consent from patients (including consent for use of patient photographs) was obtained. The most current version of the clinical trials these patients have been studied under is registered under trial identifier NCT00004044 in the public database http://www.clinicaltrials.gov (accessed February 25, 2012). This natural history diagnostic protocol studies clinical and genetic features of patients with XP, TTD, or CS. All patients have been evaluated by National Cancer Institute dermatologists (authors J.J.D. or K.H.K. since 1971) and were found to have diagnostic features of XP. The patients had a formal diagnosis of XP and attempted determination of the XP complementation group. Complementation group status was assigned as previously described using peripheral blood lymphocytes or cultured fibroblasts or lymphoblastoid cells (DiGiovanna J. Trichothiodystrophy with and without xeroderma pigmentosum. Paper presented at: Society for Investigative Dermatology Annual Meeting, May 15, 2002, Los Angeles, CA). 18,27,28 Patient identification numbers used in this study were preceded by a code for the diagnosis XP and followed by a location code “BE” indicating Bethesda, Maryland, or “DC” indicating Washington, District of Columbia, as used in previous articles (DiGiovanna J. Trichothiodystrophy with and without xeroderma pigmentosum. Paper presented at: Society for Investigative Dermatology Annual Meeting, May 15, 2002, Los Angeles, CA). 27,28 Xeroderma pigmentosum–type neurologic degeneration observed in these patients includes deterioration of neurologic status, impaired hearing, abnormal speech, ataxia, peripheral neuropathy, and loss of the ability to walk and talk. 28 Non–XP-related neurologic abnormalities observed included hypoglycinemia, traumatic hearing loss, intellectual impairment without loss of coordination, and systemic lupus erythematosus. 28 All patients with XP who had an ophthalmic examination between June 1, 1964, and December 15, 2011, at the National Institutes of Health Clinical Center were included in this report. Patients seen from 2001 to the present were examined by 1 or more of the authors (B.P.B., E.T.T., J.A.C., R.J.B., or W.M.Z.) of this article. The complete ophthalmic examinations included (when possible) best-corrected Snellen VA measurement, slit-lamp biomicroscopy, corneal endothelial cell density (ECD) by specular microscopy (Konan NONCON ROBO Pachy Specular Microscope with the KC-3009 Konan Fully Automatic Cell Analysis System), and dilated fundus examination with an indirect ophthalmoscope. Corneal fluorescein staining, 29 Schirmer’s test II (Schirmer’s test with topical anesthesia), 30 tear film breakup time (TBUT), corneal topography and thickness (Orbscan, Model DP-3002; Bausch & Lomb, Inc., Rochester, NY), and axial length measurements were performed as the patients were able, according to their age and developmental stage. For the TBUT, 5 μl of fluorescein (sodium 2% solution) was instilled using a micropipette, and the average of 3 measurements per eye is reported. Whenever possible, a central area of the cornea without structural abnormality was chosen for assessment. A TBUT ≤5 seconds is considered abnormally rapid. 31 Schirmer’s test II values >10 mm/5 minutes indicate normal baseline tear production, values from 6 mm/5 minutes to 10 mm/5 minutes are considered borderline deficiency, and values ≤5 mm/5 minutes confirm an aqueous-deficient dry eye categorization. 32 Ocular surface staining was graded according to the Oxford scale. 29 Charts, consult letters, and data in the patients’ medical records were reviewed, and the data were abstracted for this report. Conjunctival cytology specimens were obtained by gently rubbing a cotton-tip applicator across the locally anesthetized conjunctival surface. Cells were transferred by soaking the applicator tip in phosphate-buffered saline (pH 7.4). Slides of patient cells were stained and examined by an ophthalmic pathologist (C.C.C.). IBM SPSS Statistics software, version 19 (SPSS Inc., Chicago, IL) was used for the statistical analysis. The Fisher exact test was used for comparing rates of ectropion, lid pigmentation, conjunctival melanosis, and ocular surface cancers between patient groups (burning vs. nonburning patient groups or non-Hispanic white patients vs. patients of all other race/ethnicities). The odds ratio between lid margin keratinization and conjunctival scarring was calculated using logistic regression.
PY - 2013/7
Y1 - 2013/7
N2 - 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. Design: Retrospective observational case series. Participants: 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. Main Outcome Measures: 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. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
AB - 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. Design: Retrospective observational case series. Participants: 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. Main Outcome Measures: 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. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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U2 - 10.1016/j.ophtha.2012.12.044
DO - 10.1016/j.ophtha.2012.12.044
M3 - Article
C2 - 23601806
AN - SCOPUS:84879793316
SN - 0161-6420
VL - 120
SP - 1324
EP - 1336
JO - Ophthalmology
JF - Ophthalmology
IS - 7
ER -