The diagnosis of chronic wasting disease (CWD) relies on demonstration of the disease-associated misfolded CWD prion protein (PrPCWD) in brain or retropharyngeal lymph node tissue by immunodetection methods, e.g. ELISA and immunohistochemistry (IHC). The success of these methods relies on a quality sample of tissues, which requires both anatomical knowledge and considerable dissection to collect. As the prevalence of CWD continues to increase globally, the development of fast and cost-effective methods to detect the disease is vital to facilitate CWD detection and surveillance. To address these issues, we have evaluated third eyelids from CWD-infected deer and elk using real-time quaking induced conversion (RT-QuIC). We identified prion seeding activity in third eyelids in 24 of 25 (96%) CWD-infected white-tailed deer (Odocoileus virginianus). We detected RT-QuIC positivity in the third eyelid as early as 1 month after experimental CWD exposure. In addition, we identified prion seeding activity in third eyelids of 18 of 25 (72%) naturally exposed asymptomatic CWD-positive rocky mountain elk (Cervus canadensis nelson). We compared CWD detection by RT-QuIC and IHC in third eyelid, retropharyngeal lymph node, and brain in 10 deer in early symptomatic stage of disease. IHC detected PrPCWD deposition in third eyelid lymphoid follicles in 5 of 10 deer (50%) whereas third eyelids of all 10 animals were positive by RT-QuIC. This difference reflected in part a lower requirement for lymphoid follicle presence for seeding activity detection by RT-QuIC. In conclusion, RT-QuIC analysis of the third eyelid, an easily accessed tissue, has potential to advance CWD detection and testing compliance.

A classical brain-computer interface (BCI) based on visual event-related potentials (ERPs) is of limited application value for paralyzed patients with severe oculomotor impairments. In this study, we introduce a novel gaze independent BCI paradigm that can be potentially used for such end-users because visual stimuli are administered on closed eyelids. The paradigm involved verbally presented questions with 3 possible answers. Online BCI experiments were conducted with twelve healthy subjects, where they selected one option by attending to one of three different visual stimuli. It was confirmed that typical cognitive ERPs can be evidently modulated by the attention of a target stimulus in eyes-closed and gaze independent condition, and further classified with high accuracy during online operation (74.58% ± 17.85 s.d.; chance level 33.33%), demonstrating the effectiveness of the proposed novel visual ERP paradigm. Also, stimulus-specific eye movements observed during stimulation were verified as reflex responses to light stimuli, and they did not contribute to classification. To the best of our knowledge, this study is the first to show the possibility of using a gaze independent visual ERP paradigm in an eyes-closed condition, thereby providing another communication option for severely locked-in patients suffering from complex ocular dysfunctions.

Cutaneous leishmaniasis (CL) is a protozoan disease which is endemic in Iran. It is transmitted by the Phlebotomus sand fly. The eyelid is rarely involved possibly because the movement of the lids impedes the sand fly from biting the skin in this region. Here, we report 6 rare cases of eyelid CL. The patients were diagnosed by skin scraping, culture, and PCR from the lesions. Skin scraping examination showed Leishmania spp. amastigotes in the cytoplasm of macrophages. Culture examination was positive for Leishmania spp. PCR was positive for Leishmania major and Leishmania tropica. The lesions were disguised as basal cell carcinoma, chalazion, hordeolum, and impetigo. The patients were treated with intramuscular meglumine antimoniate (20 mg/kg/day) for at least 3 weeks. They showed a dramatic response, and the lesions almost completely disappeared. We emphasized the importance of clinical and diagnostic features of lesions, characterized the phylogenetic relationship of isolated parasites, and reviewed the literature on ocular leishmaniasis.

Rho-associated kinase (ROCK) I mediates signaling from Rho to the actin cytoskeleton. To investigate the in vivo functions of ROCK-I, we generated ROCK-I-deficient mice. Loss of ROCK-I resulted in failure of eyelid closure and closure of the ventral body wall, which gave rise to the eyes open at birth and omphalocele phenotypes in neonates. Most ROCK-I(-/-) mice died soon after birth as a result of cannibalization of the omphalocele by the mother. Actin cables that encircle the eye in the epithelial cells of the eyelid were disorganized and accumulation of filamentous actin at the umbilical ring was impaired, with loss of phosphorylation of the myosin regulatory light chain (MLC) at both sites, in ROCK-I(-/-) embryos. Stress fiber formation and MLC phosphorylation induced by EGF were also attenuated in primary keratinocytes from ROCK-I(-/-) mice. These results suggest that ROCK-I regulates closure of the eyelids and ventral body wall through organization of actomyosin bundles.

To show the importance of frozen section-controlled excision to avoid the re-recurrence of recurrent basal cell carcinoma (BCC) of the eyelids.

Many East Asians apply double eyelid tape to create the double eyelid effect temporarily as a means of increasing their beauty. This study evaluated the effects of four-week wear of double eyelid tape on anterior ocular health in young adult women with single eyelids. Twenty-nine participants who met the inclusion criteria were recruited. The participants' anterior ocular health was examined including blinking characteristics (blink pattern and blink rate), ocular surface health (presence of corneal abrasion, corneal staining, conjunctival staining, corneal curvatures, meibomian gland dysfunction), tear break up time, intraocular pressure, and subjective comfort level. Participants were required to apply the double eyelid tape for at least eight hours a day and five days a week for four weeks. The parameters were re-measured at the end of each week. There was a significant increase in conjunctival staining, corneal staining, and meibomian gland dysfunction, with a significant reduction in tear break-up time and intraocular pressure. By week 3, all participants had incomplete blinks. There was no significant change in symptoms and subjective comfort level reported. Therefore, patients and eye care practitioners should be aware of the potential implications of double eyelid tape wear on ocular health, with no significant change in subjective comfort.

Waved with open eyelids 2 (woe2) is a novel autosomal recessive mouse mutation that arose spontaneously in our animal facility. Upon initial evaluation, mutant mice exhibited eyelids open at birth (EOB) and wavy fur phenotypes. The goals of this study were to phenotypically characterize the woe2 mice and to identify the gene harboring the mutation responsible for the woe2 phenotype.

A model of circadian phototransduction was published in 2005 to predict the spectral sensitivity of the human circadian system to narrow-band and polychromatic light sources by combining responses to light from the spectral-opponent "blue" versus "yellow" cone bipolar pathway with direct responses to light by the intrinsically photosensitive retinal ganglion cells. In the model, depolarizing "blue" responses, but not hyperpolarizing "yellow" responses, from the "blue" versus "yellow" pathway are combined with the intrinsically photosensitive retinal ganglion cell responses. Intrinsically photosensitive retinal ganglion cell neurons are known to be much slower to respond to light than the cone pathway, so an implication of the model is that periodic flashes of "blue" light, but not "yellow" light, would be effective for stimulating the circadian system. A within-subjects study was designed to test the implications of the model regarding retinal exposures to brief flashes of light. The study was also aimed at broadening the foundation for clinical treatment of circadian sleep disorders by delivering flashing light through closed eyelids while people were asleep. In addition to a dark control night, the eyelids of 16 subjects were exposed to three light-stimulus conditions in the phase delay portion of the phase response curve while they were asleep: (1) 2-second flashes of 111 W/m(2) of blue (λmax ≈ 480 nm) light once every minute for 1 hour, (2) 131 W/m(2) of green (λmax ≈ 527 nm) light, continuously on for 1 hour, and (3) 2-second flashes of the same green light once every minute for 1 hour. Inferential statistics showed that the blue flash light-stimulus condition significantly delayed circadian phase and significantly suppressed nocturnal melatonin. The results of this study further our basic understanding of circadian phototransduction and broaden the technical foundations for delivering light through closed eyelids during sleep for treating circadian sleep disorders.

We aimed to evaluate the effect of warming eyelids on tear-film stability and quality of life (QoL) in video display terminal (VDT) users. A prospective study was conducted and 45 volunteers with ocular symptoms and tear-film instability associated with VDT use were randomly allocated into the study (n = 22) or control groups (n = 23). Subjects in the study group used eyelid warming steamer (EWS) for 2 weeks and tear fluorescein breakup time (TBUT) after single and 2-week EWS treatment, Schirmer I test, ocular surface staining scores, meibomian gland assessment, severity of dry eye disease (DED) and QoL scores after 2-week EWS treatment were analysed. The TBUT improved after both single and 2-week EWS treatment (P = 0.023 and 0.027, respectively) in the study group. The ocular surface staining scores were significantly decreased only in the study group (P = 0.038). About 60% DED patients in the study group shifted towards non-DED and the pattern of distribution was significantly different compared to baseline (P < 0.001). The QoL scores significantly improved in the study group (P = 0.002) with a negative correlation with TBUT. In conclusion, in VDT users with short TBUT, eyelid warming steamer is effective in improving tear-film stability and QoL.

Both subciliary and transconjunctival approaches have been used for decades to visualise the site of the maxillofacial fracture. The most common complication following those procedures is lower eyelids malposition.

In recent years, autologous fat grafting (AFG), also known as fat transfer or lipofilling, has been widely performed for periorbital rejuvenation and defect correction, although the evidence regarding its efficacy and safety is still lacking. Besides, with respect to the periorbital region, it is invariably the earliest appearance area of the facial aging phenomenon. Therefore, a systematic review and meta-analysis is needed to evaluate the efficacy and safety of this technique.

Members of the Krüppel-like family of transcription factors regulate diverse developmental processes in various organs. Previously, we have demonstrated the role of Klf4 in the mouse ocular surface. Herein, we determined the role of the structurally related Klf5, using Klf5-conditional null (Klf5CN) mice derived by mating Klf5-LoxP and Le-Cre mice. Klf5 mRNA was detected as early as embryonic day 12 (E12) in the cornea, conjunctiva and eyelids, wherein its expression increased during development. Though the embryonic eye morphogenesis was unaltered in the Klf5CN mice, postnatal maturation was defective, resulting in smaller eyes with swollen eyelids that failed to separate properly. Klf5CN palpebral epidermis was hyperplastic with 7-9 layers of keratinocytes, compared with 2-3 in the wild type (WT). Klf5CN eyelid hair follicles and sebaceous glands were significantly enlarged, and the meibomian glands malformed. Klf5CN lacrimal glands displayed increased vasculature and large number of infiltrating cells. Klf5CN corneas were translucent, thicker with defective epithelial basement membrane and hypercellular stroma. Klf5CN conjunctiva lacked goblet cells, demonstrating that Klf5 is required for conjunctival goblet cell development. The number of Ki67-positive mitotic cells was more than doubled, consistent with the increased number of Klf5CN ocular surface epithelial cells. Co-ablation of Klf4 and Klf5 resulted in a more severe ocular surface phenotype compared with Klf4CN or Klf5CN, demonstrating that Klf4 and Klf5 share few if any, redundant functions. Thus, Klf5CN mice provide a useful model for investigating ocular surface pathologies involving meibomian gland dysfunction, blepharitis, corneal or conjunctival defects.

The existence of multipotent adipose-derived stem cells isolated from human orbital fat (OF) tissue has shown great therapeutic potential in tissue engineering and regenerative medicine. But the use of stem cells for therapeutic applications is influenced by their proliferative and differentiation potentials, which may be affected by the age of the donor. So far there is little knowledge about the effects of donor age on the biological properties of human orbital adipose-derived stem cells (OASCs). The intraorbital fat protrusion in the lower eyelids occurs as an aging process, and the protruded fat is routinely removed during aesthetic surgeries. Based on the ease of OF harvest and the availability of OASCs, we investigated in this study the relationship between age and the differentiation and proliferation potentials of human OASCs. Human orbital adipose samples were harvested from young (with normal lower eyelid appearance) and old donors (having protruded fat pads in the lower eyelids). The morphological properties of orbital adipocytes were assessed and the fat cell size displayed a decreasing trend with advancing age. OASCs were isolated from the fat samples, expanded in vitro and cultured under appropriate inducive conditions. Compared to the young cells, although no difference was found in the cell yield and phenotype expression, aged OASCs showed fewer progenitor cell numbers, reduced proliferative rates, increased senescent features and decreased differentiation potentials towards adipogenic, osteogenic and chondrogenic lineages. Our data suggested that using autologous OASCs from elderly patients for potential therapeutic purposes might be restricted.

Meibomian gland orifices (MGOs) are located along the eyelid margin and secrete meibum into the tear film. The profile of resident innate immune cells (ICs) at this site is not well understood. The distribution and phenotype of resident ICs around MGOs in mice was investigated and herein defined as MGO-associated immune cells (MOICs). The effect of topical 0.1% benzalkonium chloride (BAK) on MOICs was also assessed. Eyelids from healthy CD11ceYFP and Cx3cr1gfp/gfp mice aged three or seven months were compared. ICs were identified as CD11c+, Cx3cr1+, and MHC-II+ using four-colour immunostaining and confocal microscopy. MOIC density was variable but clustered around MGOs. There were more CD11c+ MOICs in three-month-old compared with seven-month-old mice (three-month-old: 893 ± 449 cells/mm2 vs. seven-month-old: 593 ± 493 cells/mm2, p = 0.004). Along the eyelid margin, there was a decreasing gradient of CD11c+ MOIC density in three-month-old mice (nasal: 1003 ± 369 cells/mm2, vs. central: 946 ± 574 cells/mm2, vs. temporal: 731 ± 353 cells/mm2, p = 0.044). Cx3cr1-deficient mice had two-fold fewer MHC-II+ MOICs, suggesting a role for Cx3cr1 receptor signaling in meibomian gland surveillance. CD11c+ MOIC density was lower in BAK-exposed eyes compared to saline-treated controls, suggesting a change in homeostasis. This study provides novel insight into resident ICs located at MGOs, and their contribution to MG homeostasis.

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are considered to play a crucial role in synaptic plasticity in the developing visual cortex. In this study, we established a rat model of binocular form deprivation by suturing the rat binocular eyelids before eye-opening at postnatal day 14. During development, the decay time of excitatory postsynaptic currents mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors of normal rats became longer after eye-opening; however, the decay time did not change significantly in binocular form deprivation rats. The peak value in the normal group became gradually larger with age, but there was no significant change in the binocular form deprivation group. These findings indicate that binocular form deprivation influences the properties of excitatory postsynaptic currents mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the rat visual cortex around the end of the critical period, indicating that form stimulation is associated with the experience-dependent modification of neuronal synapses in the visual cortex.

The epidermal growth factor receptor (EGFR) signaling has a pivotal role in the regulation of morphogenesis during development and maintenance of homeostasis in adult eyelid and its adnexa. Studies have demonstrated that during eyelid morphogenesis the EGFR signaling pathway is responsible for keratinocyte and mesenchymal cell proliferation and migration at the eyelid tip. For meibomian gland morphogenesis, EGFR signaling activation stimulates meibomian gland epithelial cell proliferation. EGFR signaling pathway functions through multiple downstream signals such as ERK, Rho/ROCK and integrin and is regulated by a variety of upstream signals including Adam17, GPR48 and FGFR signaling. Herein we review the literature that describe the role of EGFR and its related signaling pathways in eyelid and meibomian gland morphogenesis.

To describe a modified technique of white line advancement posterior ptosis surgery and to report the success rate of the procedure.

Thyroid eye disease (TED) is the most common autoimmune disease and usually occurs in patients with hyperthyroidism. In this disease, eye-related tissue, such as eye muscles, eyelids, tear glands, etc., become inflated, which causes the eyes and eyelids to become red, swollen, and uncomfortable. The pathophysiology of this disease is still poorly known.

Sproutys (Sprys) are downstream targets and negative feedback regulators of the FGF-Ras-ERK signaling pathway. Our previous studies have shown that Spry1 and Spry2, through negative modulation of FGF-ERK signaling, allow lens vesicle separation from the overlying ectoderm and regulate corneal epithelial proliferation. Here we show that Spry1 and Spry2 are necessary for eyelid closure. Murine palpebral conjunctival epithelial cells that differentiate as inner eyelids and adjacent mesenchymal cells express Spry1 and Spry2 prior to eyelid closure. Conditional deletion of both Spry1 and Spry2, but not either one alone, in the ocular surface epithelial cells result in the "EOB" (eyes open at birth) phenotype suggesting redundant roles for these proteins during eyelid closure. Spry mutant eyelids show increased proliferation of conjunctival epithelial cells with concomitant induction of FGF targets, Erm, Pea3 and Dusp6 and elevated ERK phosphorylation. Peridermal cells at the leading edge of Spry-mutant eyelids showed reduced c-Jun, but not ERK, phosphorylation, reduced F-actin polymerization and reduced motility in vitro. Spry mutant eyelids also showed disruptions in epithelial mesenchymal interactions reflected in the enhanced mesenchymal Spry1 and Spry4 expression, disaggregation of BMP4-positive mesenchymal cells and loss of Shh in the eyelid epithelium. Spry mutant eyelids also showed increased Wnt signaling and reduced expression of Foxc1 and Foxc2, two transcription factors previously shown to be necessary for eyelid closure. Collectively, our results show that conjunctival epithelial Spry1 and Spry2 redundantly promote eyelid closure by (a) stimulating ERK-independent, c-Jun-mediated peridermal migration, (b) suppressing conjunctival epithelial proliferation through FGF-ERK signaling, (c) mediating conjunctival epithelial-mesenchymal interactions and (d) maintaining expression of Foxc1 and Foxc2.

Introduction. Adhesive tapes are used for taping eyelids closed and securing endotracheal tubes during general anesthesia. These tapes can cause facial skin injury. We compared the incidence of facial skin injury and patient satisfaction with different tapes used. Methods. A total of 60 adult patients at risk of skin trauma were randomized to use 3M™ Kind Removal Silicone Tape or standard acrylate tapes: 3M Durapore (endotracheal tube) and Medipore (eyelids). Patients were blinded to tape used. Postoperatively, a blinded recovery nurse assessed erythema, edema, and denudation of skin. Anesthesiologist in charge also assessed skin injury. On postoperative day 1, patients rated satisfaction with the condition of their skin over the eyelids and face on a 5-point Likert scale. Results. More patients had denudation of skin with standard tapes, 4 (13.3%) versus 0 with silicone tape (p = 0.026) and in anesthesiologist-evaluated skin injury 11 (37%) with standard versus 1 (3%) with silicone (p = 0.002). No significant differences were found in erythema and edema. Patient satisfaction score was higher with silicone tape: over eyelids: mean 3.83 (standard) versus 4.53 (silicone), Mann-Whitney U test, p < 0.001; over face: mean 3.87 (standard) versus 4.57 (silicone) (p < 0.001). Conclusion. Silicone tape use had less skin injury and greater patient satisfaction than standard acrylate tapes.