Ophthalmic Assessment in Patients With Darier Disease


To assess the prevalence of ophthalmic findings in patients with Darier disease, an autosomal dominant genetic skin disorder, in an effort to evaluate the need for eye examinations in the management of the disease.


Prospective observational case series.


Thirty-six individuals with Darier disease were evaluated by both ocular assessment questionnaire and a comprehensive ophthalmic examination (visual acuity, refraction, external examination, and slit-lamp examination) with emphasis on the eyelids, conjunctiva, and cornea. In addition, questionnaire-based medical interview and skin examination were conducted.


According to the medical questionnaire, 39% of patients reported eye problems, 36% dry eye, and 42% eye fatigue after prolonged reading. Ocular examination revealed Darier disease lesions on the eyelids in 55% of the patients, blepharitis in 44%, conjunctival hyperemia in 28%, and short tear film break-up time in 83%. There was no significant relationship between any of these ophthalmic findings and systemic retinoid therapy, sex, or age.


The high prevalence of blepharitis and dry eye highlights the importance of ophthalmologic evaluation of patients with Darier disease.

D arier disease (DD) is a rare autosomal dominant inherited skin disease characterized by hyperkeratotic papules and plaques, prominent nails, and mucous membrane involvement. The mutations responsible for DD have been identified in the ATP2A2 gene on chromosome 12q23-24.1. This gene encodes the sarco/endoplasmic reticulum Ca 2+ -ATPase type 2 isoform (SERCA2), which transports Ca 2+ from the cytosol into the endoplasmic reticulum lumen and plays a pivotal role in intracellular calcium signaling. , In addition to characteristic skin manifestations, DD has been associated with several extracutaneous manifestations, such as salivary gland obstruction, and various neuropsychiatric conditions, among them epilepsy, learning disabilities, and psychiatric disorders. Ophthalmic involvement has been described in 1 study and only a small number of case reports

Blackman and associates assessed involvement of eyelids and cornea in patients with DD. They found ocular abnormalities in 16 of 21 DD patients, including unique peripheral corneal opacities, central corneal surface irregularities, and keratotic plaques on the eyelids. The peripheral epithelial opacities varied greatly in appearance, ranging from a teardrop shape to tiny, clustered oval lesions resembling animal tracks. In 2 patients, trephine biopsy of the opacities showed epithelial edema, especially of the basal cells, and thickened basement membrane.

Case reports of ophthalmic findings in DD included retinitis pigmentosa in 2 brothers, staphylococcal conjunctivitis in 1 patient, recurrent herpes simplex virus keratitis and episcleritis in 1 patient, and eyelid lesions resembling nodular basal cell carcinoma in 2 patients.

The aim of the present study was to assess the prevalence of ocular findings in patients with DD.


Study Population

Thirty-six patients with biopsy-proven DD were recruited for the study from the Dermatology Department at Emek Medical Center. Exclusion criteria were age below 18 years and pregnancy.

The median age of the 36 patients with DD was 47 ± 14 years, range 18-85 years; 21 (60%) patients were male; 32 (91%) were Jewish and 4 (9%) were Arab; 18 (52%) had intermediate or severe DD.

Study Design

Participants were invited individually to a meeting with the study supervisor (R.P.D-G.), during which inclusion criteria were verified, the study was explained, and signed informed consent was obtained. Sociodemographic and clinical data were collected in a questionnaire-based medical interview followed by a skin examination (Supplemental Appendix 1, available at AJO.com) conducted by the same dermatologist (R.P.D-G.). An ophthalmic evaluation was then performed by an ophthalmologist (E.A.), including both an ocular assessment questionnaire and an ophthalmic examination (Supplemental Appendix 2, available at AJO.com). The study protocol was approved by Emek Medical Center’s institutional ethics committee.



An interview based on a structured questionnaire designed for the study collected information on sociodemographic and clinical data (Supplemental Appendix 1) and ophthalmologic manifestations of the disease, as well (Supplemental Appendix 2).

Cutaneous examination

Cutaneous examination of the skin, hair, nails, and mucous membranes was performed by a single dermatologist (the primary investigator, R.P.D.-G.).

Ophthalmic examination

The examination included the following: objective refraction using an autorefractometer; visual acuity testing with and without correction and using a pinhole occluder; examination of the external eye, specifically the eyelids, by unaided observation and a slit lamp; ocular biomicroscopy (slit-lamp) of the conjunctiva and cornea; tear film break-up time, slit-lamp photography of the cornea and conjunctiva to document pathology (as needed); corneal tomography using a Pentacam HR (Oculus, Wetzlar, Germany); intraocular pressure; corneal endothelial cell count using an EM-3000 (Tomey, Nagoya, Japan); and dilated eye examination to document any pathology of the lens and posterior segment.

Statistical Analysis

The data were analyzed by SAS version 9.4 (SAS Institute Inc, Cary, North Carolina, USA). A P value of 5% was considered significant. Categorical data were reported as numbers (%) and compared using χ 2 test or Fisher exact test as appropriate. Continuous variables were reported as median ± SD and range.


Questionnaire Results

The results of the ocular assessment questionnaire are summarized in Table 1 .

Table 1

Results of Ocular Assessment Questionnaire in 36 Patients With Darier Disease

Ocular Symptom N (%)
Ocular problem 14 (39)
Eye infection 13 (36)
Dry eye 13 (36)
Tiredness after reading 15 (42)
Need for glasses 21 (58)

Responses refer to symptoms experienced during the month preceding the interview.

Ophthalmic Examination Results

The results of the ophthalmic examination are reported in Tables 2 and 3 . The major findings were DD skin lesions on the eyelids ( Figure 1 ), moderate-to-severe degrees of blepharitis, and conjunctival redness ( Table 2 ). Results of tear film break-up time are presented in Table 3 . There was also 1 case of corneal neovascularization, and 1 patient was referred to clinical follow-up owing to a suspicious corneal lesion. Intraocular pressure was normal in all cases, and no stromal edema or retina or optic nerve findings were noted.

Jul 10, 2021 | Posted by in OPHTHALMOLOGY | Comments Off on Ophthalmic Assessment in Patients With Darier Disease

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