Use of digital displays and ocular surface alterations: A review

Digital display use has been accepted to be implicated as a contributing factor for dry eye disease (DED). Abnormal blinking during computer operation, including a reduced blink rate and an incomplete eyelid closure, increased palpebral fissure as consequence of high visualization angles, and meibomian gland dysfunction associated to long-term display use, are behind the increased prevalence of dry eye signs and symptoms found in digital display users. Previous research reveals significant reductions in tear volume and stability, alterations in tear film composition, including increased osmolarity, inflammatory cytokines, oxidative stress markers and reduced mucin secretion, eyelid abnormalities and ocular surface damage, encompassing corneal and conjunctival staining and bulbar redness, as a direct consequence of digital display use. In this regard, individual differences in the way that the various digital displays are typically set up and used may account for differences in their effects on induced dryness signs and symptoms. Furthermore, factors such as the use of contact lenses or inappropriate working environments, usually accompanying the use of displays, may significantly increase the prevalence and the severity of induced dry eye. Other factors, such as old age and female gender are also relevant in the appearance of associated alterations. Finally, clinicians should adopt a treatment strategy based on a multidirectional approach, with various treatments being applied in conjunction.     

Mesenchymal stromal cells for the treatment of ocular autoimmune diseases

Mesenchymal stromal cells, commonly referred to as MSCs, have emerged as a promising cell-based therapy for a range of autoimmune diseases thanks to several therapeutic advantages. Key among these are: 1) the ability to modulate innate and adaptive immune responses and to promote tissue regeneration, 2) the ease of their isolation from readily accessible tissues and expansion at scale in culture, 3) their low immunogenicity enabling use as an allogeneic “off-the-shelf” product, and 4) MSC therapy's safety and feasibility in humans, as demonstrated in more than one thousand clinical trials. Evidence from preclinical studies and early clinical trials indicate the therapeutic potential of MSCs and their derivatives for efficacy in ocular autoimmune diseases such as autoimmune uveoretinitis and Sjögren's syndrome-related dry eye disease. In this review, we provide an overview of the current understanding of the therapeutic mechanisms of MSCs, and summarize the results from preclinical and clinical studies that have used MSCs or their derivatives for the treatment of ocular autoimmune diseases. We also discuss the challenges to the successful clinical application of MSC therapy, and suggest strategies for overcoming them.     

Medication use and dry eye symptoms: A large,hypothesis-free,population-based study in the Netherlands

PurposeTo date, population-based studies reporting associations between dry eye disease and medications were hypothesis-driven, did not take into account underlying comorbidities, and did not investigate individual drugs. The purpose of this study was to clarify the association of dry eye symptoms with medication classes and individual drugs, using a hypothesis-free approach.Methods79,606 participants (age 20–97 years, 59.2% female) from the population-based Lifelines cohort in the Netherlands were cross-sectionally assessed for dry eye symptoms using the Womens’ Health Study dry eye questionnaire. All medications used were coded with the ATC classification system. Logistic regression was used to assess the risk of the 59 most-used therapeutic/pharmacological subgroups and the 99 most-used individual drugs (all n > 200) on dry eye symptoms, correcting for age, sex, body mass index, and 48 comorbidities associated with dry eye.ResultsThirty-eight (64%) medication subgroups and fifty-two (53%) individual drugs were associated with dry eye symptoms (P < 0.05), after correction for age and sex only. A multivariable model correcting for comorbidities revealed highly significant associations between dry eye symptoms and drugs for peptic ulcer (particularly proton pump inhibitors (PPIs)), antiglaucoma and anticholinergic medications.ConclusionsThis study underlines that medication use is highly informative of risk of dry eye symptoms. Correction for underlying comorbidities is critical to avoid confounding effects. This study confirms suggested associations between medications and dry eye symptoms at a population level and shows several new associations. The novel link between PPIs and dry eye symptoms deserves particular attention given how commonly they are prescribed.     

Corneal lymphangiogenesis in dry eye disease is regulated by substance P/neurokinin-1 receptor system through controlling expression of vascular endothelial growth factor receptor 3

PurposeTo evaluate the role of substance P (SP)/neurokinin-1 receptor (NK1R) system in the regulation of pathologic corneal lymphangiogenesis in dry eye disease (DED).MethodsImmunocytochemistry, angiogenesis assay, and Western blot analysis of human dermal lymphatic endothelial cells (HDLECs) were conducted to assess the involvement of SP/NK1R system in lymphangiogenesis. DED was induced in wild-type C57BL/6 J mice using controlled-environment chamber without scopolamine. Immunohistochemistry, corneal fluorescein staining, and phenol red thread test were used to evaluate the effect of SP signaling blockade in the corneal lymphangiogenesis. The expression of lymphangiogenic factors in the corneal and conjunctival tissues of DED mouse model was quantified by real-time polymerase chain reaction.ResultsNK1R expression and pro-lymphangiogenic property of SP/NK1R system in HDLECs were confirmed by Western blot analysis and angiogenesis assay. Blockade of SP signaling with L733,060, an antagonist of NK1R, or NK1R-targeted siRNA significantly inhibited lymphangiogenesis and expression of vascular endothelial growth factor (VEGF) receptor 3 stimulated by SP in HDLECs. NK1R antagonist also suppressed pathological corneal lymphangiogenesis and ameliorated the clinical signs of dry eye in vivo. Furthermore, NK1R antagonist effectively suppressed the lymphangiogenic factors, including VEGF-C, VEGF-D, and VEGF receptor 3 in the corneal and conjunctival tissues of DED.ConclusionsSP/NK1R system promotes lymphangiogenesis in vitro and NK1R antagonism suppresses pathologic corneal lymphangiogenesis in DED in vivo.     

The physical and mental burden of dry eye disease: A large population-based study investigating the relationship with health-related quality of life and its determinants

PurposeThis large cross-sectional population-based study investigated the relationship between dry eye disease (DED) and health-related quality of life (HR-QoL).MethodsDry eye and HR-QoL were assessed in 78,165 participants (19–94 yrs, 59.2% female) from the Dutch population-based Lifelines cohort, using the WHS and the SF36 questionnaire, respectively. Logistic regression was used to assess the relationship between DED and below median Physical Component Summary (PCS) and Mental Component Summary (MCS) score, corrected for age, sex, education, BMI, and 52 comorbidities.ResultsOverall, 8.9% of participants had DED. Participants with DED had an increased risk of low PCS (OR 1.54 (95% CI 1.46–1.62)) and MCS scores (OR 1.39 (95% CI 1.32–1.46)), corrected for age and sex. This risk remained significant after correction for comorbidities (P < 0.0005). Increasing DED symptom frequency was associated with decreasing HR-QoL (P < 0.0005). Undiagnosed DED subjects had a significantly increased risk of low mental HR-QoL with increasing dry eye symptoms compared to diagnosed subjects (P < 0.0005). Compared to allergic conjunctivitis, glaucoma, macular degeneration and retinal detachment, DED showed the highest risk of low HR-QoL. Compared to other common systemic and chronic disorders, such as depression, rheumatoid arthritis, and COPD, DED was distinctive by having a substantial reduction in both PCS and MCS.ConclusionDED is associated with substantial reductions in both physical and mental HR-QoL, also after correction for associated comorbidities. Not having a diagnosis is associated with worse mental HR-QoL in subjects with severe DED. Our results underline the importance of recognizing dry eye as a serious disorder.     

人工泪液对LASIK与LASEK术后干眼症状及泪膜稳定性的影响

目的：探究激光辅助原位角膜磨镶术(LASIK)和激光上皮角膜磨镶术(LASEK)术后配合0.1%玻璃酸钠(HA)治疗对干眼症状及泪膜稳定性的影响。

方法：将2017-02/2017-12纳入的230例460眼近视患者分为LASIK组和LASEK组,然后将每个治疗组随机分为0.1% HA治疗亚组和无HA亚组,两个亚组均在角膜屈光手术后应用0.3%加替沙星和0.5%氯替泼诺。观察各组患者不同时间点干眼症状评分、角膜知觉反应、角膜荧光染色(FL)、基本泪液分泌试验(SⅠt)和泪膜破裂时间(BUT)的变化。

结果：LASIK和LASEK患者术后1wk, 1、3、6mo, 0.1% HA治疗组与无HA组的FL、干眼症状评分和角膜知觉反应均存在显著差异(P<0.05)。各组术后1wk BUT均较术前明显下降。术后其他观察时间点BUT及各时间点术后SⅠt水平虽低于术前水平,但仍在正常范围内。LASEK术后患者的干眼主观症状、泪膜稳定性和角膜表面知觉优于LASIK患者,尤其是在术后1wk, 1、3mo。

结论：两种屈光手术可引起不同程度的干眼症状,LASEK组干眼症状在术后早期较LASIK组轻。早期足量使用不含防腐剂的0.1% HA可有效促进角膜修复,对术后干眼症状有很大帮助。     

Associations between ocular and extra-ocular assessment in primary Sjögren's syndrome*

ObjectivesTo assess associations between ophthalmological features and the main systemic biomarkers of primary Sjögren's Syndrome (pSS), and to identify systemic biomarkers associated with severe keratoconjunctivitis sicca (KCS) in pSS patients.MethodsIn this cross-sectional study, data was retrospectively extracted from the monocentric cohort of the French reference centre for pSS. We analysed data from the initial visit of patients admitted for suspicion of pSS and included patients validating pSS ACR/EULAR classification criteria. Ophthalmological assessment included Schirmer's test, tear break-up time, ocular staining score (OSS), and visual analogue scale (DED-VAS) for dry eye disease (DED) symptoms. Results of minor salivary gland biopsy, unstimulated whole salivary flow rate, anti-SSA/Ro antibodies, anti-SSB/La antibodies, and rheumatoid factor (RF) were collected.ResultsA total of 253 patients (245 females) with confirmed pSS, aged 56.6 ± 13.0 years, were included, among which 37% had severe KCS. Multivariate analysis showed that the presence of anti-SSA/Ro antibodies, anti-SSB/La antibodies and RF were associated with conjunctival OSS (odds ratio–OR– = 1.25 per OSS unit increase; confidence interval–CI–95% = 1.05–1.49; P = 0.01; OR = 1.31 per OSS unit increase; CI95% = 1.09–1.58, P = 0.002, and OR = 1.34 per OSS unit increase; CI95% = 1.12–1.59; P = 0.001, respectively). Both anti-SSB/La antibodies and DED-VAS ≥ 5 were significantly associated with severe KCS (OR = 2.03; CI95% = 1.03–4.00; P < 0.05 and OR = 2.52, CI95% = 1.31–4.90; P < 0.01, respectively).ConclusionAssociation between conjunctival OSS and systemic biomarkers of pSS indicate the crucial importance of conjunctival staining when pSS is suspected as a cause of DED. Conversely, patients with anti-SSB and DED-VAS ≥ 5 features should be prioritized for extensive evaluation by an ophthalmologist due to their association with severe KCS.     

盐酸溴己新吸入粉雾剂的质量与稳定性考察

摘 要 目的：评价自制的盐酸溴己新吸入粉雾剂的质量并考察其稳定性。方法: 采用冷冻干燥 气流粉碎法制备盐酸溴己新吸入粉雾剂,考察其吸湿性及临界相对湿度;测定其粒径和水分并观察粉末形态;检查其细微粒子剂量和递送剂量均一性;开展盐酸溴己新吸入粉雾剂稳定性考察。结果:所制备的盐酸溴己新吸入粉雾剂的临界相对湿度为65%,空气动力学粒径<5 μm,粉末含水量<2%,细微粒子剂量＞30%,递送剂量均一性符合药典要求;稳定性试验中各指标在观察期内无明显变化。结论:所制备的盐酸溴己新吸入粉雾剂适合肺部吸入给药,且具有较好的稳定性。     

星点设计-效应面法优化盐酸溴己新吸入粉雾剂的处方

摘 要 目的：优化盐酸溴己新吸入粉雾剂的处方。方法: 采用冷冻干燥 气流粉碎法制备盐酸溴己新吸入粉雾剂,通过星点设计考察甘露醇（X1）,亮氨酸（X2）和泊洛沙姆188（X3）在辅料中的用量对盐酸溴己新吸入粉雾剂的休止角（Y1）、细微粒子剂量（Y2）和空气动力学粒径（Y3）的影响。根据最佳数学模型绘制效应面,通过重叠等高线图确定最优处方。结果:影响因素和考察指标之间存在定量关系,优化处方为甘露醇：亮氨酸：泊洛沙姆188在处方中的比例为2.4∶〖KG-*2〗2.22∶〖KG-*2〗0.05。较优处方的各指标实测值与预测值较接近。结论:采用星点设计 效应面法完成了盐酸溴己新吸入粉雾剂的多目标同步优化。     

Hyperbaric gaseous cryotherapy: effects on skin temperature and systemic vasoconstriction

OBJECTIVE: To compare skin-surface cooling caused by the application of an ice bag (15min) and the projection of carbon dioxide microcristals (2min) under high pressure (75 bar) and low temperature (-78 degrees C), a modality called hyperbaric gaseous cryotherapy. DESIGN: Randomized controlled trial with repeated measure. SETTING: Laboratory experiment. PARTICIPANTS: Twelve healthy male subjects (mean +/- standard deviation, 22.9+/-1.8y). INTERVENTIONS: Ice bag and hyperbaric gaseous cryotherapy were randomly applied on the skin of the nondominant hand. MAIN OUTCOME MEASURE: Skin temperature of the cooled (dorsal and palmar sides) and contralateral (dorsal side) hands were continuously measured with thermistor surface-contact probes before, during, and after (30min) cooling. RESULTS: Hyperbaric gaseous cryotherapy projection induced a large decrease (P<.05) of the dorsal skin temperature of the cooled hand (from 32.5 degrees +/-0.5 degrees C to 7.3 degrees +/-0.8 degrees C) and a significant decrease of the skin temperature of the palmar side and of the contralateral hand. The skin temperature of the dorsal side of the cooled hand was decreased with an ice bag (from 32.5 degrees +/-0.6 degrees C to 13.9 degrees +/-0.7 degrees C, P<.05). However, the lowest temperature was significantly higher than during hyperbaric gaseous cryotherapy, and no significant changes in the other skin temperatures were observed. Rewarming was equal after the 2 modalities, highlighting a more rapid increase of the skin temperature after hyperbaric gaseous cryotherapy. CONCLUSIONS: Hyperbaric gaseous cryotherapy projection decreased the skin temperature of the cooled and contralateral hand, suggesting a systemic skin vasoconstriction response. On the other hand, the vascular responses triggered by ice pack cooling appeared limited and localized to the cooled area.