Safety and feasibility of mesenchymal stem cell therapy in patients with aqueous deficient dry eye disease

PurposeTo evaluate the safety and feasibility of injecting allogeneic adipose-derived mesenchymal stem cells (ASCs) into the lacrimal gland (LG) as a treatment of aqueous deficient dry eye disease (ADDE).MethodsIn this open-label, 5-visit clinical trial (baseline, treatment and weeks 1, 4 and 16) seven subjects with ADDE received one transconjunctival injection of allogeneic ASCs into the LG in one eye. The ASC product contained 22 million ASCs/ml and the injected volume was maximally 50% of the LG volume as determined on magnetic resonance imaging (MRI). Treatment related adverse events (AEs) were assessed at each visit (primary endpoint). Ocular Surface Disease Index (OSDI), tear osmolarity, tear film breakup time (TBUT), corneal staining (Oxford grade) and Schirmer's I test were assessed at each timepoint.ResultsNo AEs related to the study treatment were observed. Mean follow-up time was 126 days after treatment. The mean OSDI score decreased from 58.9 ± 20.6 at baseline to 34.1 ± 21.6 (p < 0.002). In the study eye mean tear osmolarity decreased from 312.9 ± 10.4 to 291.6 ± 10.9 mosm/l (p < 0.002), mean TBUT increased from 3.7 ± 1.5 to 7.1 ± 1.9 s (p < 0.002), mean Schirmer's I test increased from 4.6 ± 0.7 to 8.1 ± 3.1 mm/5 min (p < 0.03), while mean Oxford grade showed a trend towards a decrease from 2.4 ± 0.7 to 1.3 ± 1 (p < 0.10).ConclusionOur trial suggests that injection of allogeneic ASCs into the LG is a safe and feasible treatment of severe ADDE. A randomized placebo-controlled trial aimed at elucidating the therapeutic effect of allogeneic ASCs in a larger patient cohort from our research group is currently underway.     

Association between the levels of prostaglandin E2 in tears and severity of dry eye

AIM: To investigate the relationship between the levels of prostaglandin E2 (PGE2) in tears and dry eye disease severity based on both clinical symptoms and signs. METHODS: Tear samples were collected from 36 non-Sjögren syndrome dry eye patients (10 males and 26 females, mean age 50.11±11.17y). All participants completed the Ocular Surface Disease Index (OSDI) questionnaire and underwent a detailed ophthalmic examination including, tear film breakup time (TBUT), ocular surface fluorescein staining, Schirmer I test, and meibomian gland assessment. The level of PGE2 in tears was measured using enzyme-linked immunosorbent assay (ELISA). The independent associations between tear PGE2 levels and other variables including demographics, OSDI scores, TBUT, Schirmer scores, ocular surface staining scores, and stage of meibomian gland dysfunction (MGD) were evaluated using linear regression analysis. RESULTS: The mean PGE2 level in tears of dry eye patients was 537.85±234.02 pg/mL. The tear PGE2 levels significantly positively correlated with OSDI scores (R=0.608, P<0.001), however, they did not significantly associate with TBUT (R=0.153, P=0.373), Schirmer scores (R=-0.098, P=0.570), ocular surface staining scores (R=0.282, P=0.095), and stage of MGD (R=-0.107, P=0.535). Male sex was significantly negatively correlated with tear PGE2 levels. CONCLUSION: The levels of PGE2 in tears are positively correlated with dry eye symptoms. However, no significant association was found between tear PGE2 levels and the results of other common dry eye diagnostic tests.     

Human precorneal tear film and lipid layer dynamics in meibomian gland dysfunction

PurposeTo evaluate the precorneal tear film (PCTF) and lipid layer (TFLL) thicknesses and thinning rates in meibomian gland dysfunction (MGD) using a combined ultra-high-resolution optical coherence tomography (OCT) and thickness dependent fringe (TDF) interferometry system.MethodsBased on the Tear Film and Ocular Surface Society (TFOS) International Workshop on Meibomian Gland Dysfunction diagnostic algorithm, the Ocular Surface Disease Index (OSDI) and meibum grade score (MGS) were used to classify subjects into four groups: Normal (OSDI<13 and MGS<10), MGD (OSDI≥13 and MGS≥10), Asymptomatic MGD (OSDI<13 and MGS≥10), and Mixed (OSDI≥13 and MGS<10). The OCT/TDF system was used to capture PCTF and TFLL thicknesses and thinning rates. Kruskal-Wallis was used to compare median PCTF and TFLL thicknesses and thinning rates.ResultsThere were 190 subjects categorized into four groups: Normal (n = 63), MGD (n = 51), Asymptomatic MGD (n = 29), and Mixed (n = 47). The PCTF was significantly thinner in the Mixed group (3.3 [1.2]) than in the Normal (p < 0.001), MGD (p < 0.001) and Asymptomatic MGD (p = 0.009) groups. Relative to the Normal (4.5 [4.5] μm/min) and Mixed (5.0 [2.0] μm/min) groups, the rate of PCTF thinning was faster in the MGD (8.1 [3.0] μm/min, both p < 0.001) and Asymptomatic MGD (6.9 [3.1] μm/min, p = 0.009 and p = 0.04, respectively) groups. The correlation between PCTF thinning rate and TFLL thickness was ρ = −0.46, p < 0.001.ConclusionsSymptomatic and asymptomatic MGD shows rapid PCTF thinning rates (evaporation), while the PCTF thickness was reduced in mixed disease. Thicker lipid layers were associated with slower PCTF thinning.     

Randomised double-masked placebo-controlled trial of the cumulative treatment efficacy profile of intense pulsed light therapy for meibomian gland dysfunction

PurposeTo assess long-term cumulative treatment effects of intense pulsed light (IPL) therapy in meibomian gland dysfunction (MGD).MethodsEighty-seven symptomatic participants (58 female, mean ± SD age, 53 ± 16 years) with clinical signs of MGD were enrolled in a prospective, double-masked, parallel-group, randomised, placebo-controlled trial. Participants were randomised to receive either four or five homogeneously sequenced light pulses or placebo treatment to both eyes, (E-Eye Intense Regulated Pulsed Light, E-Swin, France). Visual acuity, dry eye symptomology, tear film parameters, and ocular surface characteristics were assessed immediately before treatment on days 0, 15, 45, 75, and four weeks after treatment course completion on day 105. Inflammatory and goblet cell function marker expression, and eyelid swab microbiology cultures were evaluated at baseline and day 105.ResultsSignificant decreases in OSDI, SPEED, and SANDE symptomology scores, and meibomian gland capping, accompanied by increased tear film lipid layer thickness, and inhibited Corynebacterium macginleyi growth were observed in both treatment groups (all p < 0.05). Sustained clinical improvements occurred in both treatment groups from day 75, although significant changes from day 45, in lipid layer quality, meibomian gland capping, OSDI and SANDE symptomology, were limited to the five-flash group (all p < 0.05).ConclusionsIPL therapy effected significant improvements in dry eye symptomology, tear film lipid layer thickness, and meibomian gland capping in MGD patients. Five-flash IPL treatment showed superior clinical efficacy to four-flash, and an initial course of at least four treatments is suggested to allow for establishment of sustained cumulative therapeutic benefits prior to evaluation of overall treatment efficacy.Trial registration numberACTRN12616000667415.     

Short tear film breakup time-type of dry eye in India

Purpose:The aim of this study was to describe the clinical characteristics and risk factors of short tear film break-up time (TBUT) type of dry eye disease and compare it with other types of dry eye diseases.Methods:This cross-sectional study included 570 patients (≥ 20 years) from the outpatient department using systematic random sampling.Results:The age-adjusted prevalence of short TBUT type of dry eye disease was 5.4% (95% confidence interval: 3.2–6.8%). There was no difference (P > 0.05) between the total and subscale scores of the Ocular Surface Disease Index^® questionnaire between patients with short TBUT and those with aqueous tear deficiency. Both these groups differed significantly (P < 0.05) in the findings of TBUT, Schirmer I test, and Lissamine green staining score. The common symptoms in patients with short TBUT type of dry eye disease were eye fatigue (25.4%), heaviness in the eye (19.7%), and an uncomfortable sensation (14.1%). The symptoms in the aqueous tear deficiency group were light sensitivity (28.2%), dryness (19.2%), burning (13.0%), foreign body sensation (12.8%), and blurring of vision (14.1%). The risk factors associated with short TBUT type of dry eye disease were the presence of meibomian gland dysfunction (odds ratio: 3.759 [95% confidence interval: 2.135–6.618], P < 0.0001) and female sex [odds ratio: 1.954 (95% confidence interval: 1.042–3.667), P = 0.037].Conclusion:Patients with short TBUT type of dry eye disease have symptom severity similar to aqueous tear-deficient dry eyes, but the pattern is different. The finding of this type of dry eye disease in India indicates its global presence, and ophthalmologists should consider it in their differential diagnoses.     

Effect of chronic anti-glaucoma medications and trabeculectomy on tear osmolarity

Purpose

To evaluate the tear film osmolarity (TFO) and ocular surface clinical signs and symptoms in chronically medicated glaucoma patients and post-trabeculectomy patients.

Methods

This is a single-center, prospective case-controlled study. One-hundred and thirty eyes of 130 participants aged ≥45 years were included (49 normal controls, 50 glaucoma patients on chronic preserved anti-glaucoma medication ≥6 months, and 31 post-trabeculectomy patients not on medication ≥6 months). TFO, tear break-up time (TBUT), Schirmer''s test I and dry eye symptoms were evaluated. Data from both groups of glaucoma patients were compared with age and sex-matched controls. Logistic regression was performed to calculate the odds ratios.

Results

Mean TFO in the three groups were 301.4±7.7, 307.0±9.3, and 307.4±11.6 mOsm/l, respectively. Compared with normal controls, chronically medicated glaucoma patients and post-trabeculectomy patients were more likely to have a raised TFO, with odds ratios (95% CI) of 4.43 (1.74–11.32) and 2.76 (1.02–7.94), respectively. Both groups of glaucoma patients were also more likely to experience dry eye symptoms, with ORs of 4.72 (1.92–11.59) and 4.24 (1.54–11.72). There was no significant difference in TFO and symptoms between both groups of glaucoma patients, and in TBUT and Schirmer''s test across all three groups.

Conclusions

Patients on chronic topical anti-glaucoma medication and post-trabeculectomy patients were more likely to have raised TFO and dry eye symptoms, suggesting significant ocular surface disease. Glaucoma practitioners should be aware that dry eye symptoms and raised TFO may occur in the absence of TBUT and Schirmer''s test abnormality.     

Effects of dietary high dose DHA omega-3 supplement in dry eye with meibomian gland dysfunction

AIM: To evaluate the clinical efficacy of dietary supplement of high dose DHA omega-3 in dry eye with meibomian gland dysfunction (MGD). METHODS: Prospective randomized double-masked, placebo-controlled clinical trial was conducted in mild to moderate dry eye patients with MGD. Patients have no history of taking any dietary omega-3 supplements before 3mo. Patients were divided into two groups: 24 patients in the omega-3 group and 26 patients in the placebo group. The omega-3 group received two capsules of Easyeye Dry®, total containing 600 mg of EPA and 1640 mg of DHA, while the placebo group received two capsules containing 3000 mg of olive oil. All patients take two pills once a day. The examination of MGD scores, tear break-up time (TBUT), corneal staining test (NEI), strip meniscometry (SM tube), and ocular surface disease index (OSDI) scores were performed at baseline, after 4 and 8wk. RESULTS: A total of 50 patients were included. There were no differences in baseline characteristics between the two groups, such as age, sex, and other ocular examination findings. The TBUT, NEI, and OSDI scores significantly improved after 4 and 8wk in both groups. While after 8wk TBUT (6.00±1.62s vs 5.08±1.28s, P=0.034) and MGD score (7.2±1.8 vs 8.1±2.6, P=0.033) in the omega-3 group was more significantly improved than that of the placebo group. CONCLUSION: Dry eye with the MGD patient, a high dose of DHA omega-3 dietary supplement can improve TBUT and MGD score after 8wk, effective in stabilizing the tear film.     

Dry anophthalmic socket syndrome – Standardized clinical evaluation of symptoms and signs

ObjectivesTo assess symptoms and signs of the dry anophthalmic socket syndrome (DASS) in a standardized manner.Methods87 unilateral anophthalmic patients were evaluated using the Ocular Surface Disease Index (OSDI), the 5-Item Dry Eye Questionnaire (DEQ-5), and a modified version of Symptom Assessment iN Dry Eye (SANDE) questionnaire separately for the anophthalmic socket and for the healthy fellow eye. Conjunctival inflammation was semi-quantitatively graded and Schirmer I test with topical anesthesia was performed bilaterally. The correlations between scores of the dry eye questionnaires and the results of the Schirmer tests, conjunctival inflammation, and demographic data were examined.ResultsPatients had significantly higher OSDI, DEQ-5 and SANDE scores at the anophthalmic side compared to the healthy eye (p ≤ 0.019, respectively). 63% of patients complained of anophthalmic socket dryness in at least one of the three questionnaires. Patients had higher inflammation (p < 0.001) and more tear volume in the Schirmer I test with topical anesthesia (p ≤ 0.024) on the anophthalmic side compared to the fellow eye.ConclusionsMost anophthalmic patients have significantly more subjective dryness complaints on their anophthalmic side compared to the healthy fellow eye, even in absence of tear deficiency and clinical blepharitis. Eye care practitioners should consider the diagnosis criteria and the definition for DASS proposed in this study, when counseling anophthalmic patients. However, research should be undertaken to investigate the role and the interactions of causative etiological causes for DASS. Furthermore, there is a high priority to establish a standardized examination protocol and to develop an evidence-based treatment algorithm for DASS.     

Efficacy and retention of silicone punctal plugs for treatment of dry eye in patients with and without ocular graft-versus-host-disease

PurposeTo examine the retention rates and efficacy of silicone punctal plugs for the treatment of dry eye disease (DED) in patients with ocular graft-versus-host-disease (oGVHD) in comparison to dry eye disease due to non-oGVHD etiologies.MethodsWe reviewed the case-records of 864 consecutive patients with DED who were symptomatic despite topical therapy and had silicone punctal plugs placed over an eight-year- period at a single academic center. We compared plug retention rates in oGVHD and non-oGVHD DED patients using Kaplan–Meier analyses. Furthermore, we analyzed changes in objective ocular surface parameters including tear breakup time (TBUT), Schirmer's test, and corneal fluorescein staining (CFS) score in plug-retaining patients at two-, six- and twelve-month follow-up.ResultsMedian age of dry eye patients was 58 years, and 606 (70%) of patients were women. In the cohort, 264 (31%) patients were diagnosed with oGVHD. Plug retention was significantly lower in oGVHD-DED patients compared to non-oGVHD-DED patients (p < 0.0001). We observed significant improvement in CFS scores in plug retaining-oGVHD and non-oGVHD DED patients at all time points. Tear break-up time was significantly prolonged at six- and twelve-months follow-up in non-oGVHD patients, whereas significant change in TBUT in oGVHD patients was recorded only at twelve months post plug placement. Schirmer's score improved significantly in plug retaining-non-oGVHD DED patients at six- and twelve-months follow-up, however no significant change was observed in Schirmer's score in oGVHD DED patients.ConclusionsAn improvement in ocular surface disease parameters was observed in both plug-retaining oGVHD and non-oGVHD DED patients. However, a majority of oGVHD DED patients spontaneously lost their punctal plugs within 90 days of placement. Therefore, regular follow-up after plug placement is recommended to detect plug loss and ensure adequate disease control.     

Sex and age differences in symptoms and signs of dry eye disease in a Norwegian cohort of patients

PurposeTo investigate sex and age differences in symptoms and signs in a Norwegian clinic-based cohort of patients with dry eye disease (DED).MethodsVisitors at the Norwegian Dry Eye Clinic were examined using Ocular Surface Disease Index (OSDI) questionnaire score, tear osmolarity, tear break-up time (TFBUT), ocular surface staining, corneal sensitivity, Schirmer I test, and meibum expressibility (ME) and quality (MQ). A diagnosis of DED was made by an ophthalmologist based on symptoms and signs, and only DED patients were enrolled in the study: 1823 patients (338 males; mean age 51.2 ± 16.2 years; 1485 females; mean age 52.5 ± 16.0 years). The patients were divided into age subgroups: 20–39 years, 40–59 years and ≥60 years. Sex differences in the aforementioned tests were analyzed. Values were reported as mean ± standard deviation (SD), and intergroup comparisons were performed using Mann-Whitney U test. Multiple regression was used to analyze sex and age influences on symptoms and signs.ResultsWhen patients of all ages were analyzed, females had increased osmolarity, shorter TFBUT, reduced MQ and ME and higher corneal sensitivity. OSDI, Schirmer I test, ocular surface staining and corneal staining were not significantly different between the sexes. Only with TFBUT and ME were the sex difference present in all age subgroups. Multiple regression showed that all parameters were influenced by either sex or age, but only TFBUT and ME were influenced by both sex and age. (all p < 0.05).ConclusionsSex and age differences in dry eye were most consistent in TFBUT and ME, that indicate differences in meibomian gland functionality. Sex and age subgroup stratification is important in future studies investigating DED in other populations.     

Effects of meibomian gland dysfunction and aqueous deficiency on friction-related disease

PurposeTo evaluate the effects of meibomian gland dysfunction (MGD) and aqueous deficiency (AD) on friction-related disease (FRD).MethodsCross-sectional comparative study. This study included 550 eyes (550 patients) with dry eye disease (DED). The DED subtype and dynamic tear-film parameters by automated assessments were investigated for the analysis of FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy).ResultsPatients with FRD had a higher proportion of moderate-to-severe MGD and AD (p < 0.001 and p < 0.001, respectively). The dropout rate of the meibomian gland was higher (30.5 ± 31.8 and 14.1 ± 25.0%, p < 0.001), tear meniscus height (TMH) was lower (227.8 ± 60.4 and 241.7 ± 55.6 μm, p = 0.008), and he first non-invasive keratographic tear break-up time (NIKBUT-1) was shorter (5.9 ± 3.5 and 7.3 ± 3.7 s, p < 0.001) in patients with FRD than in those without FRD. In the logistic regression analysis with clinical manifestation, both moderate-to-severe MGD and AD were associated with FRD (odds ratios [OR] 12.27, 95% confidence interval [CI] 7.72–19.50, and 2.31, 95% CI 1.43–3.71], p < 0.001 and p < 0.001, respectively). The dropout rate was positively associated with FRD (OR 1.017, 95% CI 1.010–1.023, p < 0.001). TMH and NIKBUT-1 were negatively associated with FRD (OR 0.995, 95% CI 0.991–0.999, and 0.90, 95% CI 0.85–0.95, p = 0.039 and p < 0.001, respectively).ConclusionsThis study showed that FRD was highly associated with MGD and meibomian gland dropout rate, suggesting that FRD may be mainly affected by lipid components. AD and TMH also had a good but relatively lower association with FRD, compared to MGD and meibomian gland dropout rate.     

热敷按摩改善睑板腺功能障碍患者的白内障术后疗效

目的：评价白内障术前进行眼睑热敷联合睑板腺按摩对白内障合并轻中度睑板腺功能障碍（MGD） 患者白内障术后临床效果的改善。方法：前瞻性临床研究。收集2019年9月至2020年6月于温州医科大学附属眼视光医院杭州院区就诊的50～85岁轻中度MGD合并白内障的患者,按随机数字表法分为实验组和对照组,实验组先接受3次眼睑热敷联合睑板腺按摩治疗再行白内障手术,对照组直接行白内障手术。分别记录MGD治疗前、治疗后以及白内障术后1周、1个月、3个月时的泪液分泌试验（SⅠT）、泪膜破裂时间（TBUT）、角结膜染色评分、睑板腺功能评分;眼表综合分析仪（keratograph 5M）检查并记录非侵入性泪河高度（NITMH）、非侵入性泪膜破裂时间（NITBUT）和睑板腺缺失范围（MGL）;采用眼表疾病指数（OSDI）问卷得分进行评估。使用广义估算方程（GEE）、广义线性混合模型（GLMM）、独立样本t检验及Mann-Whitney U检验进行数据分析。结果：共纳入77例（77眼）, 最终纳入分析68例（68眼）,每组34例。实验组在MGD治疗后,睑缘形态、睑板腺排出能力、SⅠT、 TBUT及OSDI评分较MGD治疗前明显好转（P<0.05）;角膜点染在白内障术后1周时较治疗前增加 （P=0.002）,至术后1个月时恢复至治疗前水平。组间比较发现,实验组睑脂质量变化量在白内障术后各时间点均明显优于对照组（P<0.05）;白内障术后1周时,实验组睑缘形态的变化量小于对照组, 术后1个月时,NITMH变化量小于对照组,而OSDI评分变化量大于对照组（P<0.05）,实验组症状及体征更轻;对照组在白内障术后1周时,睑缘形态及SⅠT明显变差,至术后1个月时恢复至术前水平; 睑脂质量在术后1周时变差,NITMH在术后1个月时减少,二者至术后3个月时恢复至术前水平。结论： 白内障术前采用眼睑热敷联合睑板腺按摩治疗MGD,可改善术后睑板腺功能状态,缓解干眼症状。     

Changes in conjunctival mucin expressions in patients with first diagnosis of dry eye and its clinical significance北大核心CSCD

目的了解首诊干眼患者结膜黏蛋白MUC1、MUC4、MUC5AC和MUC16表达情况及其与干眼症状体征的相关性。方法采用横断面研究方法,于2016年12月至2018年5月在厦门大学附属厦门眼科中心、首都医科大学附属北京同仁医院、四川大学华西医院和上海市普陀区中心医院4个临床研究中心纳入首次就诊干眼患者69例69眼作为干眼组,正常志愿者40例40眼作为正常对照组。受检者均填写中国干眼问卷、眼表疾病指数量表(OSDI)和干眼相关生活质量评分问卷(DEQS),以评估干眼相关症状;采用泪膜破裂时间(TBUT)检查、角结膜荧光素钠染色、基础泪液分泌试验(Schirmer试验Ⅰ)以评估干眼相关体征;采用结膜印迹细胞学方法采集结膜细胞,采用实时荧光定量PCR法检测受检者结膜中MUC1、MUC4、MUC5AC和MUC16 mRNA表达情况;采用Spearman秩相关分析探讨结膜黏蛋白表达量与干眼症状体征之间的关联。结果干眼组患者结膜黏蛋白MUC1和MUC16 mRNA相对表达量分别为3.277(0.568,5.790)和1.815(1.048,3.694),均较正常对照组的1.055(0.550,2.010)和1.024(0.541,1.965)升高,差异均有统计学意义(Z=819.00,P=0.008;Z=861.00,P=0.002)。根据OSDI症状分级,轻中度干眼(评分12-32)以MUC1表达升高为主[3.277(1.161,6.226),Z=9.04,P=0.029],重度干眼(评分>32)主要以MUC16表达升高为主[1.968(1.074,3.726),Z=12.24,P=0.007]。MUC1 mRNA相对表达量与TBUT呈正相关,与角膜染色评分和角结膜染色评分呈负相关(r s=0.270,P=0.025;r s=-0.331,P=0.006;r s=-0.325,P=0.007)。MUC16 mRNA相对表达量与TBUT呈正相关,与视物模糊症状评分、阅读时症状加重评分、开夜车影响程度评分、使用计算机影响程度评分及看电视影响程度评分均呈负相关(r s=0.249,P=0.039;r s=-0.359,P=0.047;r s=-0.370,P=0.034;r s=-0.558,P=0.016;r s=-0.498,P=0.006;r s=-0.515,P=0.002)。结论干眼患者结膜黏蛋白MUC1与MUC16 mRNA表达水平升高,MUC1 mRNA表达与患者体征相关,MUC16 mRNA表达与患者的生活质量相关。     

Dry eye disease in children and adolescents in India

PurposeTo describe the etiological causes and clinical profile of dry eye disease (DED) among children and adolescents seeking eye care in India.MethodsThis was a cross-sectional study of 1023 new patients (≤21 years of age) diagnosed with DED presenting between 2010 and 2018 to a multi-tier ophthalmology hospital network. Children and adolescents with both symptoms and signs of dry eyes were considered as subjects. The data entry and retrieval were done using an electronic medical record system and analyzed using appropriate statistical tests.ResultsThe mean age of the patients was 15.2 ± 5.6 years and 76% were in their early and late adolescence. Overall, the main etiologies responsible for DED in children and adolescents were Meibomian gland dysfunction (MGD) in 49% of cases, Stevens-Johnson Syndrome (SJS) in 33% and Vitamin A deficiency (VAD) in 9%. Aqueous deficiency dry eye (ADDE) because of SJS and VAD accounted for most of the cases in infancy (92%), toddlerhood (96%), early childhood (76%) and middle childhood (68%). While Meibomian gland dysfunction (MGD) related evaporative dry eye (EDE) was the leading cause of DED in early (51%) and late adolescence (66%). Severe visual impairment and blindness was significantly greater in eyes with ADDE as compared to those with EDE (p < 0.0001), 81% of which were affected by SJS.ConclusionThe causes of and visual morbidity due to DED varied significantly in different age-groups. Most of the visual morbidity in children and adolescents was limited to eyes with ADDE due to SJS.     

Role of transient receptor potential melastatin 8 activity in menthol-induced cold sensitivity and its qualitative perception in dry eye

PurposeTo evaluate the role of transient receptor potential melastatin 8 (TRPM8) activity in menthol-induced cold sensitivity and its qualitative perception in patients with dry eye (DE).MethodsThis prospective, cross-sectional, comparative study included 52 eyes of 52 subjects (mean age: 66.8 ± 9.2 years; range: 44–86) with a tear break-up time (TBUT) of ≤5 s. The participants were classified into three groups: 17 patients with DE symptoms and keratoconjunctival (KC) staining scores of ≥3 points (positive KC-DE group), 18 patients with DE symptoms and KC staining scores of <3 points (negative KC-DE group), and 17 individuals with KC staining scores of <3 points and no symptoms (non-DE control group). The menthol-induced cool sensation (M-cool) and TBUT were measured after administration of 2 μl of 1.0 mM menthol eye drops. Furthermore, participants answered a questionnaire regarding their stimulus perception (pleasant, unpleasant, or neither).ResultsM-cool values were similar in the three groups. TBUT significantly increased in the negative KC-DE and control groups (P < 0.05) and remained unchanged in the positive KC-DE group (P > 0.05) after menthol administration. DE patients reported the sensation as pleasant or unpleasant, whereas most control participants were indifferent (P < 0.05).ConclusionsWhile M-cold sensitivity was similar in DE and control groups, its qualitative perception differed between these groups. Thus, TRPM8 activation at the peripheral level alone may not be sufficient to account for the manifestation of discomfort symptoms associated with DE.     

Clinical efficacy of 0.05% cyclosporine nano-emulsion in the treatment of dry eye syndrome associated with meibomian gland dysfunction

AIM: To evaluate the clinical efficacy of topical 0.05% cyclosporine nano-emulsion in the treatment of dry eye syndrome (DES) with meibomian gland dysfunction (MGD). METHODS: This prospective study included 64 patients with DES and MGD who were randomly assigned to three groups: Group 1 (n=24, conventional cyclosporine), Group 2 (n=21, nano-emulsion cyclosporine), and Group 3 (n=19, control). Lid margin telangiectasia (LMT), meibomian gland secretion (MGS), conjunctival injection (CI), corneal staining (CS), tear break-up time (TBUT), Schirmer test I (STI), Ocular Surface Disease Index (OSDI), and lipid layer thickness (LLT) was evaluated at 4, 8, and 12wk of treatment. RESULTS: In Group 3 (control), LMT, CS, and CI improved after 8wk, MGS, TBUT after 12wk of treatment. In Group 1 (conventional cyclosporine), LMT, MGS, and TBUT improved significantly after 4wk, whereas CS, CI, STI, and LLT improved significantly after 8wk, and OSDI at 12wk. In Group 2 (nano-cyclosporine), LMT, MGS, CS, CI, TBUT, and OSDI significantly improved after 4wk, and STI after 8wk. Especially, LLT was significantly higher than other groups after 4wk. CONCLUSION: Cyclosporine and nano-cyclosporine shows significant improvement in DES with MGD than the control group. In contrast, the nano-cyclosporine group shows more statistically improved CI and CS at 4wk, especially LLT at 4, 8, and 12wk compared to the conventional cyclosporine group.     

Tear cytokine levels in the diagnosis and severity assessment of ocular chronic graft-versus-host disease(GVHD)

PurposeTo analyse the tear cytokine levels of patients diagnosed with ocular chronic graft-versus-host disease(GVHD)and examine the consistency of these levels with different ocular surface parameters.Methods23 ocular chronic GVHD patients were selected for the assessment of tear cytokine levels and ocular surface parameters (TBUT, CFS, OSDI, and Schirmer's test), and 16 dry eye disease(DED)patients without systemic immune disease were selected as the control group. The 23 cytokines were measured using microsphere-based immunoassay analysis and their consistency with different ocular surface parameters was studied.ResultsICAM-1, IL-1β, IL-6, and IL-8 showed elevated levels in the eyes of oGVHD patients compared to DED [P < 0.001]. IL-7 and EGF showed lower levels in the eyes of patients with oGVHD than in those of patients with DED [P < 0.0001]. Furthermore, the levels of IL-6 and IL-8 showed a stronger correlation with corneal fluorescein staining (CFS) (P < 0.05), and the levels of IL-6 and ICAM-1 were most consistent with fluorescein tear film break-up time (TBUT) (P < 0.05).ConclusionsOur study demonstrated certain tear cytokines, including ICAM-1, IL-1β, IL-6, IL-8 IL-7 and EGF, as promising new possible diagnostic markers of chronic oGVHD and criteria for chronic ocular GVHD severity. Because tear sampling is noninvasive and simple, this method is expected to be an overwhelming applicable for the screening and diagnosis of chronic GVHD.     

Association of meibomian gland morphology with symptoms and signs of dry eye disease in the Dry Eye Assessment and Management (DREAM) study

PurposeTo describe associations between symptoms and signs of dry eye disease (DED) and meibomian gland (MG) morphology.MethodsCross-sectional study utilizing data from the Dry Eye Assessment and Management (DREAM) Study. Readers graded MG features in the middle third of upper and lower lids on infrared meibography images. Associations with signs and symptoms of DED were evaluated with adjustment for age and sex.ResultsAmong 268 patients, no MG features were associated with symptom scores (p > 0.08). Among 394 upper eyelids, better tear break-up times (<2, >2- <3.2and ≥ 3.2 s) were associated with more tortuous glands (mean (SD) 0.58(0.95), 0.83(1.2) and 1.14 (1.4), p = 0.01) and with higher scores on a composite score of MG features (21.90 (9.76), 23.29 (9.50), 26.26 (10.27); p = 0.02). Longer Schirmer test wetting lengths (0–5, >5–10, and >10 mm) were associated with increasing composite scores (22.02 (9.29), 23.80 (10.34), 24.96 (9.96), p = 0.03). Patients with Sjogren syndrome compared to other patients had fewer distorted MGs (mean 3.4 (2.3) vs 4.3 (2.3), p = 0.03) and fewer ghost glands (mean 0.33 (0.88) vs 0.89 (1.8), p = 0.006) in the upper lid.ConclusionIn the DREAM study, most MG morphologic features were not associated with the severity of DED symptoms or signs. Tortuous glands and a higher composite score for MG features were associated with longer tear break-up times and longer Schirmer test length in the upper eyelid only. Patients with Sjogren syndrome had fewer distorted and ghost glands.     

Assessment of the Tear Film Lipid Layer Thickness after Cataract Surgery

Purpose: To evaluate changes in the tear film lipid layer thickness (LLT) after cataract surgery and the effects of cataract surgery on dry eye syndrome (DES) and meibomian gland dysfunction (MGD). Methods: LLT measurements obtained using the LipiView interferometer, tear break-up time (TBUT) measurements, Schirmer’s tests, Oxford staining scores, lid margin and meibomian gland findings, and the Ocular Surface Disease Index (OSDI) questionnaire scores were evaluated before and one and three months after cataract surgery. Results: Forty-three eyes (43 patients) were included. LLT was significantly thinner one month after surgery than at baseline (P = 0.004). TBUT was significantly shorter at both one (P < 0.001) and three (P < 0.001) months after surgery than at baseline. OSDI scores were significantly higher (P < 0.001) and the meibum quality was significantly poorer (P = 0.001) at one month after surgery than at baseline. TBUT was significantly and positively correlated with LLT (r = 0.29, P < 0.001), while the OSDI (r = ?0.38, P < 0.001) and Oxford staining (r = ?0.30, P = 0.001) scores and the meibum quality (r = ?0.21, P = 0.01) were significantly and negatively correlated with LLT. Conclusions: The tear film LLT was significantly thinner and DES and MGD parameters showed deterioration after cataract surgery. In addition, LLT was significantly correlated with DES and MGD parameters. These results suggest that clinicians should consider the tear film lipid layer while managing the exacerbation of DES after cataract surgery.