Prostaglandin-Associated Periorbitopathy in Children and Young Adults with Glaucoma.

OBJECTIVE: To evaluate for relative palpebral and orbital changes after long-term unilateral exposure to prostaglandin analogues (PGAs) in patients with childhood glaucoma. DESIGN: Prospective cross-sectional cohort study. PARTICIPANTS: A total of 29 patients with history of childhood glaucoma, who were treated unilaterally with PGAs for at least 12 months. METHODS: Based on 4 standardized clinical photographs (en face with eyes open, right and left side views with eyes open, and en face with eyes closed), 3 masked expert graders each independently selected the eye they perceived to have received unilateral PGA treatment by physical appearance alone and graded the following features relative to the other eye: (1) ocular (e.g., conjunctival hyperemia, iris heterochromia, and buphthalmos), (2) palpebral (e.g., eyelash trichomegaly, eyelash hypertrichosis, eyelid erythema, eyelid edema, eyelid hyperpigmentation, high upper eyelid crease, upper eyelid ptosis, upper and/or lower eyelid retraction, and eyelid skin atrophy with presence of telangiectasias), and (3) periorbital (e.g., superior sulcus hollowing, proptosis, enophthalmos, hypoglobus, and hyperglobus). An interrater reliability analysis was performed using the Fleiss kappa (κ) statistic to determine consistency among raters. MAIN OUTCOME MEASURES: Frequencies of each feature of prostaglandin-associated periorbitopathy (PAP); group consensus; interrater reliability of selected PGA-treatment laterality. RESULTS: Median unilateral PGA exposure time was 31.7 months (interquartile range: 18.8-44.3 months). Eyelash trichomegaly and hypertrichosis (n = 22, 76%), high upper eyelid crease (n = 20, 69%), upper eyelid ptosis (n = 14, 52%), and superior sulcus hollowing (n = 15, 52%) were the most frequently observed features of PAP in PGA-treated eyes compared with untreated fellow eyes. Most of these changes were mild, but 20% to 30% of patients exhibited moderate eyelash and/or eyelid changes. One patient had severe PAP after long-term unilateral PGA exposure. Group consensus with correctly selected laterality was achieved in all patients. The inter-rater reliability was excellent (κ = 0.815, P < 0.001, 95% confidence interval [0.605, 1.000]). CONCLUSIONS: Mild-to-moderate changes in the ocular adnexa can develop in children and young adults with long-term PGA exposure. Patients and their families should be educated on the possibility of PAP, especially when initiating monocular PGA therapy.

[Demodex and ocular surface disease]. / Demodex et pathologies de la surface oculaire.

Demodex is a saprophytic mite of the ocular adnexa, which can in certain circumstances proliferate on the skin of the face and on the eyelid margins. It is involved in facial rosacea (especially in the papulopustular form) and in the development or aggravation of anterior and/or posterior blepharitis or even keratoconjunctivitis, often in association with cutaneous lesions ; the pathophysiology is often multifactorial. Symptoms are non-specific, but the presence of cylindrical sleeves on the eyelashes is very suggestive of infestation, and certain techniques of biomicroscopic examination or imaging, such as confocal microscopy in vivo, allow direct visualization of the parasite. Parasitological examination of the eyelashes can confirm the diagnosis and can be improved by good sampling technique. Eyelid hygiene and oil-based ointments are the cornerstone of treatment. New specific treatments, in particular topical treatments based on tea tree oil, ivermectin, as well as pulsed light therapy and micro-exfoliation of the eyelid margin, can help to reduce the parasitic load and improve symptoms.

Development of Clinician-Reported Outcome (ClinRO) and Patient-Reported Outcome (PRO) Measures for Eyebrow, Eyelash and Nail Assessment in Alopecia Areata.

BACKGROUND: Eyebrow and eyelash hair loss and nail damage-in addition to scalp hair loss-are important signs/symptoms of alopecia areata (AA) to patients and deserve assessment in AA clinical trials. OBJECTIVES: Our objective was to develop clinician-reported outcome (ClinRO) and patient-reported outcome (PRO) measures and accompanying photoguides to aid in the assessment of AA-related eyebrow, eyelash and nail signs/symptoms. METHODS: Iterative rounds of qualitative, semi-structured interviews were conducted with US expert dermatologists and North American patients with AA. Patients with eyebrow, eyelash and nail involvement were purposefully sampled. Interview transcripts were qualitatively analyzed. RESULTS: Dermatologists (n = 10) described eyebrow and eyelash loss as concerning for affected patients and, along with nail appearance, as deserving assessment. Dermatologist data informed the development of single item, 4-point Likert-type ClinRO and PRO measures of current eyebrow loss, eyelash loss and nail appearance and a PRO measure of eye irritation. Patients (n = 45, age 15-72 years) confirmed the importance and relevance of these signs/symptoms. Interim revision resulted in measures that were understood by and relevant to patients. Dermatologists (n = 5) and patients (n = 10, age 21-54 years) participated in the development of the eyebrow, eyelash and nail photoguides and confirmed that they included photos that appropriately represented different severity levels and were helpful to derive and standardize ratings across raters. CONCLUSIONS: The ClinRO and PRO measures for eyebrow, eyelash and nail appearance, with their accompanying photoguides and the PRO Measure for Eye Irritation provide clear and meaningful assessments of outcomes important to patients with AA.

Real-Time Video Microscopy of In Vitro Demodex Death by Intense Pulsed Light.

Objective: To directly observe the in vitro real-time effects of intense pulsed light (IPL) on a Demodex mite extracted from an eyelash of a patient with ocular rosacea. Background: Demodex is a risk factor in the pathogenesis of oculofacial rosacea, meibomian gland dysfunction (MGD), and dry eye disease (DED). Recent studies suggested IPL to control or eradicate Demodex organisms in the periocular area. Despite encouraging reports, the direct effect of IPL on Demodex is not well understood. Methods: An eyelash infested with Demodex was epilated from a 62-year-old female patient with oculofacial rosacea. Following isolation and adherence of a mite onto a microscope slide, real-time video microscopy was used to capture live images of the organism before, during, and after administration of IPL pulses. IPL pulses were delivered with the M22 IPL (Lumenis), with IPL settings used for treatment of DED due to MGD (the "Toyos protocol"). A noncontact digital laser infrared thermometer was used to measure the temperature of the slide. Results: Before the IPL pulses, legs of the Demodex mite spontaneously moved in a repetitive and semicircular motion. During administration of IPL, spontaneous movements of the legs continued. Immediately after administration of five IPL pulses, the temperature of the slide increased from room temperature to 49°C. Immediately afterward, the Demodex mite became completely immobilized. The legs appeared retracted, smoother, less corrugated, bulkier, and less well-defined. Movement of the Demodex mite was not observed at the hourly inspections for 5 h and after 24 h following the application of IPL pulses. Conclusions: Our video directly demonstrates the effect of IPL on a live Demodex mite extracted from a freshly epilated eyelash. The results suggest that IPL application with settings identical to those used for treatment of DED due to MGD causes a complete destruction of the organism.

Office-Based Diagnosis of Demodex Using Smartphone.

Demodex is an important pathogen in ophthalmology. It is believed to cause a variety of eyelid and eyelash diseases. Currently, light microscopes are being used for imaging demodex. However, microscopes are not available everywhere. Also, it is not cost-effective to perform light microscopy in every case. In this case, we demonstrate a new method: imaging demodex using cell phone. A 90-diopter noncontact double aspheric lens was attached to the posterior camera of the smartphone with clear tape. An eyelash of a patient with blepharitis was removed. A video was taken using smartphone. There was a moving demodex parasite in the root of the eyelash. A clear video image could be taken using the smartphone. A smartphone and a 90-diopter lens are adequate for the imaging and diagnosis of demodex.

Use of an inexpensive magnifier with light source in the diagnosis of trichiasis among community-based case finders in Nigeria.

PURPOSE: Trichiasis case finding is challenging in many trachoma endemic countries. We sought to determine how the use of an inexpensive hand-held magnifier with light source aids in the diagnosis of people with trichiasis. METHODS: We undertook a study on the use of the "Wilson", an inexpensive hand-held magnifier with light source between two groups of trained case finders: community drug distributors (CDD) volunteers and non-health volunteers. Each group was randomly allocated to be provided a Wilson or not. We compared the number of people with suspected trichiasis and the proportion of true cases referred by each group. Focus group discussions explored the perceptions of the case finders that used the Wilson on its utility in the diagnosis of trichiasis and its ease of use. RESULTS: Among the 121 case finders, 61 were CDD volunteers (31 were provided the Wilson) and 60 were non-health worker volunteers (30 were provided the Wilson). Case finders that used the Wilson were 4.57 times (95% CI 2.46-8.47) more likely to have patients presenting confirmed as trichiasis compared to those not using the Wilson. Case finders that used the Wilson felt the instrument was easy to use, enlarged the eyelashes and made diagnoses of trichiasis easier. DISCUSSION: In Nigeria it appears that the Wilson is easy to handle and use among trichiasis case finders enhances the diagnosis of trichiasis.

Rare Variants in LAMA5 Gene associated with FLT4 and FOXC2 Mutations in Primary Lymphedema May Contribute to Severity.

Mutations in the Fms-related tyrosine kinase 4 (FLT4) and forkhead box protein C2 (FOXC2) genes cause Milroy disease (MD) and lymphedema-distichiasis syndrome (LDS), respectively, but the mechanism underlying disease pathology remains unclear. Applying whole-exome sequencing to two families with MD, one LDS family, and one sporadic LDS case, we identified four rare variants in the laminin subunit alpha-5 gene (LAMA5) in subjects carrying novel and known missense FLT4 mutations and a 7-bp duplication and 1-bp insertion in FOXC2. Phenotyping was expanded in some individuals using magnetic resonance lymphangiography, indiocyanine green fluorescence lymphography, and immunofluorescent lymphatic staining of skin tissue. Skin lymphatic staining showed the existence of dermal lymphatic vasculature in the MD case. Significant lymphatic dysfunction was observed in both MD and LDS patients. In the MD patient, tortuous lymphatics in the dorsum of the foot were slowly enhanced on indocyanine green fluorescent lymphography (ICG) imaging. Dilated lymph collectors with disruption and lymph leakage were observed in the familial LDS case on magnetic resonance lymphangiography (MRL). Numerous tortuous lymph collectors were visualized along the entire length of affected lower limbs on MRL imaging, and retrograde lymph flow was observed in the lymph collectors during ICG lymphography in the isolated LDS case. The finding of rare LAMA5 variants together with FLT4 and FOXC2 mutations suggests that these mutations may be co-responsible for these disorders and most likely interfere with the function of lymphatics. Further, larger studies are needed to confirm these results.

Unilateral Poliosis of Eyelashes.

A 68-year-old man presented with significant, asymptomatic, unilateral eyelash poliosis, not associated with any ophthalmic or systemic conditions. He reported that this started about 40 years ago with a few lashes in the central portion of his eyelid and that adjacent eyelashes subsequently became involved over the next 4 to 5 days. He had normal ophthalmologic and neurologic examinations with no other relevant medical history reported. The case might be an unusual presentation of a halo nevus. To the best of the authors' knowledge, this is the first such case reported regarding the eyelashes. The case and relevant literature are presented.

Sonography in pathologies of scalp and hair.

Disorders of the scalp often result in severe cosmetic interference with quality of life, creating the need for optimal medical surveillance. We tested the latest generation of ultrasound machines in patients with scalp pathology and prepared a cross-sectional library encompassing a wide assortment of conditions. Normative data on the sonographic anatomy of scalp and human hair, and important methodological considerations, are also included.

Mutations in FOXC2 in humans (lymphoedema distichiasis syndrome) cause lymphatic dysfunction on dependency.

BACKGROUND: Human lymphoedema distichiasis syndrome (LDS) results from germline mutations in transcription factor FOXC2. In a mouse model, lack of lymphatic and venous valves is observed plus abnormal smooth muscle cell recruitment to initial lymphatics. We investigated the mechanism of lymphoedema in humans with FOXC2 mutations, specifically the effect of gravitational forces on dermal lymphatic function. METHODS: We performed (1) quantitative fluorescence microlymphangiography (FML) on the skin of the forearm (non-swollen region) at heart level, and the foot (swollen region) below heart level (dependent) and then at heart level, and (2) immunohistochemical staining of microlymphatics in forearm and foot skin biopsies, using antibodies to podoplanin, LYVE-1 and smooth muscle actin. RESULTS: FML revealed a marked reduction in fluid uptake by initial lymphatics in the LDS foot during dependency, yet normal uptake (similar to controls) in the same foot at heart level and in LDS forearms. In control subjects, dependency did not impair initial lymphatic filling. Immunohistochemical microlymphatic density in forearm and foot did not differ between LDS and controls. CONCLUSIONS: FOXC2 mutations cause a functional failure of dermal initial lymphatics during gravitational stress (dependency), but not hypoplasia. The results reveal a pathophysiological mechanism contributing to swelling in LDS.

Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24.

INTRODUCTION: Lymphoedema-distichiasis syndrome (LD) (OMIM 153400) is a rare, primary lymphoedema of pubertal onset, associated with distichiasis. Causative mutations have now been described in FOXC2, a forkhead transcription factor gene. Numerous clinical associations have been reported with this condition, including congenital heart disease, ptosis, varicose veins, cleft palate, and spinal extradural cysts. SUBJECTS: We report clinical findings in 74 affected subjects from 18 families and six isolated cases. All of them were shown to have mutations in FOXC2 with the exception of one family who had two affected subjects with lymphoedema and distichiasis and linkage consistent with the 16q24 locus. RESULTS: The presence of lymphoedema was highly penetrant. Males had an earlier onset of lymphoedema and a significantly increased risk of complications. Lymphatic imaging confirmed the earlier suggestion that LD is associated with a normal or increased number of lymphatic vessels rather than the hypoplasia or aplasia seen in other forms of primary lymphoedema. Distichiasis was 94.2% penetrant, but not always symptomatic. Associated findings included ptosis (31%), congenital heart disease (6.8%), and cleft palate (4%). Other than distichiasis, the most commonly occurring anomaly was varicose veins of early onset (49%). This has not been previously reported and suggests a possible developmental role for FOXC2 in both venous and lymphatic systems. This is the first gene that has been implicated in the aetiology of varicose veins. CONCLUSION: Unlike previous publications, the thorough clinical characterisation of our patients permits more accurate prediction of various phenotypic abnormalities likely to manifest in subjects with FOXC2 mutations.

Intravitreal cilia in phakic penetrating eye injury.

BACKGROUND: Intraocular cilia present clinical perplexity due to their radiolucency, the extremely variable ocular response to such cilia, and the inadvisability of using MRI in cases of suspected metallic intraocular foreign bodies (IOFB). METHODS: Two cases of intravitreal cilia associated with phakic penetrating eye injury are described where preoperative CT scan revealed no retained IOFB. RESULTS: B-scan ultrasonography detected intravitreal cilia in one patient and raised this suspicion in the other. One patient presented with endophthalmitis unresponsive to intravitreal antibiotics, the other with culture-negative anterior uveitis. Both underwent vitrectomy and removal of cilia. CONCLUSIONS: Intravitreal cilia should be considered in penetrating eye injuries even in phakic eyes with no radiological evidence of IOFB, especially if associated with endophthalmitis. B-scan ultrasonography may aid detection of intravitreal cilia and thus alter clinical management.