Comparison of the effects of topical levobunolol and timolol solution on the human ocular surface

PURPOSE: To compare the effects of levobunolol hydrochloride and timolol maleate on tear volume, precorneal tear film stability, and corneal epithelial barrier function in normal human eyes. SUBJECTS AND METHODS: The study population consisted of 14 healthy volunteers. To obtain pretreatment baseline values, we determined the radius of the tear meniscus (RTM) by meniscometry; the noninvasive breakup time (NIBUT) of the precorneal tear film with a tear specular microscope; and corneal fluorescein uptake with a fluorophotometer. Levobunolol hydrochloride (0.5%) or timolol maleate solution (0.5%) was instilled twice daily for 4 weeks into 1 eye; the contralateral eye was treated with the other topical drug twice daily for the same period. At the end of the study period, the same tests were performed, and the pre- and posttreatment results were compared. RESULTS: Timolol solution did, and levobunolol did not, significantly reduce NIBUT from the baseline values. RTM was significantly decreased by treatment with either timolol or levobunolol solution. Corneal fluorescein uptake was not significantly changed, although it was higher after treatment with both topical drugs. CONCLUSIONS: Four-week treatment with timolol solution resulted in significant instability of the precorneal tear film. Both timolol and levobunolol solution significantly decreased tear volume on the ocular surface. These results indicate that levobunolol solution applied twice daily has equal effects on the tear volume and corneal epithelial barrier function as does timolol solution applied twice daily and that it affects precorneal tear film stability less than timolol solution.     

Comparison of the effects of preserved and unpreserved formulations of timolol on the ocular surface of albino rabbits

Thirty-six albino rabbits, randomly divided into six groups, were used to study their ocular tolerance to (a) 0.25 and 0.50% Timoptol preserved with 0.01% benzalkonium chloride, (b) 0.25 and 0.50% Timoptol-LP, a gel-forming solution preserved with 0. 012% benzododecinium bromide, and (c) 0.25 and 0.50% Timabak unpreserved in the ABAK eyedrops dispenser. All eyedrops were applied in the right eye for 60 days. A clinical follow-up with slitlamp examination and break-up time evaluation was performed for 2 months. At the end of the experimentation, the animals were sacrificed and their eyes enucleated for histological analyses of the conjunctiva and cornea. There was no significant difference in the clinical examination between each group, except for the break-up time evaluation between Timoptol and Timabak at each concentration which was better with the unpreserved timolol. Histological results showed a significant difference in the corneal stroma edema between preserved and unpreserved timolol. This study confirms that using unpreserved timolol may be beneficial for the long-term treatment of glaucomatous patients as it increases tear film stability and decreases epithelial permeability and stromal aggression of the cornea.     

Effects of timolol maleate on tear flow in human eyes

Lacrimal function was studied in 30 patients treated for glaucoma, with 0.25% timolol eye drops. Rose bengal and fluorescein staining disclosed punctate epithelial defects in 11 eyes after one week. During the following weeks there defects disappeared spontaneously in most eyes. Schirmer tests (I and II), tear lysozyme and pre-corneal film break-up time were significantly decreased by the treatment, while tear immunoglobulins were unimpaired. The authors conclude that topical timolol treatment decreases tear production. This effect is quantitatively limited and does not appear dangerous for normal eyes, although it may become so for eyes with an originally low lacrimal secretion.     

干眼仪在干眼诊断中的价值初步评价

目的：评价干眼仪对干眼的诊断价值。方法：对25例(25只眼)正常人和35例(35只眼)干眼患者分别行泪膜破裂时间(BUT)、泪液分泌试验(Schirmer 1)、角膜荧光素染色(FL)、干眼仪检查和泪高度测量五项检查。结果：干眼患者的干眼仪检测等级与正常人差异显著(χ^2=32．22，P=0．000)。干眼仪诊断干眼的特异度为80％，灵敏度为83％。干眼仪检查为Ⅲ级脂质层形态图像者患干眼的机率约为。75％(15／25)。干眼患者的干眼仪检测等级越高，BUT和Schirmer 1试验越短(r=-0．783，-0．368，P=0．000，0．015)，角膜荧光素染色越多(r=0．806，P=0．000)，而与泪河高度无相关(P=0．178)。正常人的干眼仪检测等级也与BLrr和SchirmerI试验呈负相关(r=-0．398，-0．656，P=0．024，0．000)。干眼患者的干眼仪显示图像的稳定性较正常人差。干眼仪的检查结果具有较高的重复性。结论：干眼仪能较直观地观察角膜中央脂质层的光干涉图像，是一种快速、无创伤、重复性强、操作简单的检查方法。对干眼的诊断及客观反映病情的严重程度具有临床应用价值。     

超声乳化白内障吸除术后泪膜的变化

目的　了解超声乳化白内障吸除术对泪膜的影响。方法　随机抽取行超声乳化白内障吸除术的老年性白内障患者 6 8例 (79只眼 ) ,分别于术前 ,术后 1、2、7、14、30及 180d行泪膜破裂时间(breakuptime ,BUT)、基础泪液分泌试验 (SchirmerⅠtest,SⅠt)、角膜荧光素染色、干眼仪检查及下睑中央泪河高度检查。结果　与术前相比 ,术后 1及 2d ,BUT明显缩短 ,SⅠt、下睑中央泪河高度、角膜荧光素染色程度及干眼仪检查等级明显增高 (P <0 0 1) ;术后 7d时SⅠt,14d时下睑中央泪河高度 ,30d时BUT、角膜荧光素染色程度和干眼仪检查等级恢复至术前水平 ,与术前比较差异无显著意义(P >0 0 5 )。术后 30d ,19 3%的患眼泪膜未能恢复至术前水平 ;术前泪膜正常的患者中 1/9发生干眼。术后 1、7、14及 30d ,术前BUT <10s的术眼BUT <5s的发生率高于术前BUT≥ 10s的术眼(P <0 0 5 ) ;术后 14、30及 180d ,术前角膜荧光素染色评分 >2分的术眼术后角膜荧光素染色评分 >2分的发生率高于术前角膜荧光素染色评分≤ 2分的术眼 (P <0 0 5 ) ;术后 14d ,术前干眼仪检查等级≥Ⅲ级的术眼术后干眼仪检查等级≥Ⅲ级的发生率高于术前干眼仪检查等级 <Ⅲ级的术眼(P <0 0 5 )。结论　超声乳化白内障吸除术可影响泪膜的稳定性 ,使部分患     

Corneal barrier function, tear film stability, and corneal sensation after photorefractive keratectomy and laser in situ keratomileusis

PURPOSE: To compare corneal sensation, corneal barrier function, tear secretion, and tear film stability after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). DESIGN: Prospective, nonrandomized clinical trial. METHODS: In a prospective study, 28 eyes of 15 patients underwent PRK and 115 eyes of 59 patients underwent LASIK to correct myopia. Corneal sensation, corneal epithelial barrier function, tear secretion, and tear film stability were examined preoperatively and 1 week and 1, 3, 6, and 12 months postsurgery. RESULTS: Both PRK and LASIK significantly compromised corneal sensation, increased epithelial barrier function, reduced tear secretion, and deteriorated tear film stability (P < .05, Wilcoxon signed-rank test). Deterioration of corneal sensation was significantly greater after LASIK than after PRK by 3 months postoperatively (P < .05, Wilcoxon rank sum test). Increases in corneal epithelial permeability were more prolonged after LASIK than after PRK. A significant intergroup difference in permeability was observed 1 month after surgery (P < .01). Tear breakup time was significantly shorter in the LASIK group than in the PRK group up to 3 months after surgery (P < .045). CONCLUSIONS: LASIK induces greater and more prolonged damage to corneal sensation, corneal barrier function, and tear film stability than PRK.     

Tear film lipid layer alterations in allergic conjunctivitis

PURPOSE: To assess the alterations of the tear film lipid layer and tear functions in patients with seasonal allergic conjunctivitis (SAC) and to compare the results with healthy control subjects. METHODS: Seventy-eight eyes of 39 consecutive patients diagnosed as SAC (mean age 32.6 years; 11 male, 28 female) as well as 20 eyes of 10 healthy control subjects (mean age 32.5 years; 6 male, 4 female) underwent slit-lamp examinations, tear film breakup time measurements (BUT), corneal fluorescein stain scoring, Schirmer test, and tear film lipid layer interferometry. The 2 groups were then compared for the examined parameters. RAST and serum IgE level evaluations were also carried out in the patients to confirm the diagnosis of allergy. RESULTS: The mean BUT was 3.4 +/- 1.5 seconds in patients with SAC compared with the mean value of 12.4 +/- 2.4 seconds in the controls (P < 0.05). There were no significant differences in relation to Schirmer test values between the 2 groups; 78% of the patients with SAC had grade 3 or above dry eye change in tear film lipid layer interferometry, whereas none of the controls had an interferometry grade greater than 3 (grade 1-2 normal; grade 3-4 dry eye; grade 5 severe dry eye). Eyes with SAC had significantly higher tear film lipid layer thickness ranges compared with the control eyes (P < 0.05). CONCLUSION: SAC was associated with advanced tear instability and thickening of the tear film lipid layer. Evaluation of the tear film lipid layer thickness might be useful in the assessment of the extent of dry eye disease and the treatment outcomes in patients with allergy.     

Interleukin-1beta tear concentration in glaucomatous and ocular hypertensive patients treated with preservative-free nonselective beta-blockers

PURPOSE: To evaluate the ocular surface inflammatory response to the presence of preservatives in nonselective beta-blocker eyedrops. DESIGN: Prospective, crossover, single-masked, randomized clinical study. METHODS: study population: Twenty primary open-angle glaucoma or ocular hypertensive patients were divided in two groups, one treated with preservative-free timolol 0.5% (group 1) and the other with preserved timolol 0.5% (group 2) eyedrops. After 60 days of therapy and 3 more weeks of washout, the two groups switched to the other therapy. procedure: At each visit, basal tear samples were collected from the inferior conjunctival fornix for the determination of interleukin (IL)-1beta tear concentrations by an enzyme-linked immunosorbent assay. Intraocular pressure measurement, conjunctival hyperemia, superficial punctate keratitis, and tear film breakup time were evaluated. main outcome measure: IL-1beta concentration in tears following the use of preserved eyedrops. RESULTS: IL-1beta tear concentrations increased significantly in both groups, compared with baseline values, during preserved timolol therapy. There were no statistically significant changes in hyperemia and superficial punctate keratitis throughout the study in either group. A statistically significant breakup time reduction was observed in both groups after 30 days and after 60 days of preserved therapy. CONCLUSION: The use of preservatives in timolol 0.5% eyedrops leads to tear film instability and ocular surface inflammatory changes documented by a reduction of breakup time and an increase of IL-1beta tear concentrations. Preservative-free beta-blockers are preferable for long-term hypotensive therapy to prevent ocular surface inflammation.     

Smoking associated with damage to the lipid layer of the ocular surface

PURPOSE: To evaluate the effects of smoking on ocular surface. DESIGN: Prospective, comparative, interventional case series. METHODS: setting: Institutional. study population: Sixty smokers (33 men, 27 women) and 34 healthy subjects (18 men, 16 women) were enrolled into this study. Patients with associated ophthalmic or systemic diseases, and history of contact lens use and ocular surgery were excluded. The duration of average smoking was 13.1 years (range 5 to 35 years). INTERVENTION: Ocular surface was evaluated by measuring corneal and conjunctival sensitivity, surface staining with fluorescein, tear film breakup time, Schirmer 1 test, and conjunctival impression cytology. Dry eye symptoms were scored by questionnaire. Kinetic analysis of sequential tear interference images obtained by a DR-1 tear lipid layer interferometry was used to investigate the precorneal lipid layer spread. Results were compared with a control group. MAIN OUTCOME MEASURES: Comparison of subjective complaints with objective parameters in cigarette smokers and normal subjects. RESULTS: In the smoker group, the mean Schirmer 1 test value was 10.8 mm (range 8 to 14 mm). The mean breakup time was 5.3 seconds (range 1 to 10 seconds), the average conjunctival sensitivity was 26.2 mm (range 0 to 45 mm), and the average central corneal sensitivity was 37.6 mm (range 5 to 60 mm). There was no statistically significant difference in goblet cell densities or in Schirmer 1 test values between smokers and controls (P > .05). Higher grades of lipid layer changes were observed in smokers by DR-1 interferometry kinetic analysis. CONCLUSIONS: Smoking has deteriorating effects on the lipid layer of precorneal tear film.     

Corneal epithelial permeability of dry eyes before and after treatment with artificial tears.

PURPOSE: The question of whether artificial tears can lead to objective improvement of ocular surface disease in dry eyes is still unanswered. The aim of the current study is to assess the influence of artificial tears on corneal epithelial permeability of dry eyes. Furthermore, the effect of benzalkonium chloride, used as a preservative of artificial tears, on corneal epithelial permeability is investigated. METHODS: The corneal epithelial permeability of 40 dry eye patients (80 eyes) was measured by computerized objective fluorophotometry before and 6 weeks after treatment with artificial tears containing either polyvinyl pyrrolidone 2% without preservative (20 patients) or polyvinyl pyrrolidone 2% preserved with benzalkonium chloride 0.005% (20 patients). RESULTS: Before treatment, the epithelial permeability of the dry eye patients was found to be 2.7 times that of a control group. After treatment, the epithelial permeability of patients treated with unpreserved polyvinyl pyrrolidone 2% had decreased significantly (-37%; P less than 0.001), whereas patients who had been treated with polyvinyl pyrrolidone 2% preserved with benzalkonium chloride 0.005% showed an increase in epithelial permeability (+21%; P = 0.05%). CONCLUSION: These data suggest that, in dry eyes, treatment with unpreserved artificial tears may lead to an objective improvement in corneal surface disease. However, this effect may be counteracted by preservation of tear substitutes with benzalkonium chloride.     

2型糖尿病患者干眼症发生情况及相关因素探讨

目的：分析2型糖尿病患者并发干眼症情况及相关影响因素。

方法：选取45例90眼2型糖尿病患者和40例80眼非糖尿病患者为研究对象,分析其泪膜破裂时间、基础泪液分泌试验以及角膜荧光素染色指标间的差异,并分析其相关因素。

结果：观察组患者平均泪膜破裂时间为6.23±2.36s,显著短于对照组; 泪液分泌试验滤纸条平均浸润长度为8.65±3.82mm,显著低于对照组; 角膜荧光素染色评分为1.89±1.31分,显著高于对照组; 干眼症发病率达58%,显著高于对照组,差异均具有统计学意义(P<0.05)。Logistic多因素分析显示泪液基础分泌量和泪膜破裂时间为2型糖尿病患者合并干眼症重要的危险因素。

结论：2型糖尿病患者泪膜破裂时间缩短、基础泪液分泌值减少以及角膜荧光素染色评分升高。泪液基础分泌量和泪膜破裂时间为2型糖尿病患者合并干眼症重要的危险因素。     

Basal tear turnover and topical timolol in glaucoma patients and healthy controls by fluorophotometry.

To assess the effect of glaucoma and timolol on tear secretion, basal tear turnover was measured with fluorophotometry in 13 open-angle glaucoma patients not using any ophthalmic medication, 24 patients using timolol medication daily, and 41 healthy control subjects. Basal tear turnover is defined as the tear turnover at the lowest level of reflex lacrimation possible under physiologic conditions. Tear turnover was calculated from the decay of the tear fluorescence after instillation of fluorescein. Minimal influence of reflex lacrimation was obtained by instilling 1 microliter of 2% fluorescein without touching the eye and by discarding measurements performed in the first 5 min. Minimization was confirmed by a monophasic decay of tear fluorescence. The values of patients who used timolol and those who did not use timolol were significantly lower than those of healthy control subjects (mean values in percent/minute +/- standard deviation: 10.1 +/- 3.2, 12.3 +/- 4.1, and 15.6 +/- 5.4, respectively; Student's t-test: P < 0.02). The values of patients who used timolol were significantly lower compared to those of patients who did not use timolol (P = 0.03). The tear film break up time values of patients who used timolol were significantly shorter than those of patients who did not use timolol and healthy control subjects (Fisher exact test: P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)     

Tear thinning time and topical anesthesia as assessed using the HIRCAL grid and the NCCA.

BACKGROUND: The literature contains conflicting reports of the effects of topical anesthetics on tear film stability, with some consensus that unpreserved topical anesthetics are less likely to reduce tear film stability than preserved preparations. This experiment investigated the effect of unpreserved 0.4% benoxinate hydrochloride on tear thinning time (TTT), in parallel with "real time" corneal sensitivity assessment. METHODS: Tear film stability was assessed (HIRCAL grid) in parallel with real time assessment of the pharmacological activity (NCCA) of unpreserved 0.4% benoxinate hydrochloride in normal eyes. RESULTS: The anesthetic used did not significantly affect tear film stability. This finding is in agreement with previous investigators. CONCLUSIONS: Unpreserved 0.4% benoxinate hydrochloride could be used to facilitate tear film stability assessment. The experimental protocol used could also be applied to investigate the temporal relationship between anesthesia and tear film stability with preserved topical anesthetics that have been found to decrease tear film stability.     

Temporal progression and spatial repeatability of tear breakup.

PURPOSE: This study used image analysis to compare the temporal progression and spatial reoccurrence of the area of tear film breakup (AB) in dry eye and normal subjects. METHODS: Tear breakup was induced in 10 control and 10 dry eye subjects during the Staring Tear Breakup Dynamics (S-TBUD) test, which involves keeping one eye open for as long as possible, termed the maximum blink interval (MBI). Video imaging of tear film fluorescence measured the onset and progression of the AB. AB location and area were mapped. The progression of ABs from the first trial, the rate of tear breakup or dry area growth rate (DAGR), and the overlap of ABs in three successive trials 5 minutes apart were computed by custom MATLAB programs. RESULTS: The final AB before the blink was significantly greater (average, 30.7%+/-12.5% vs. 16.1%+/-9.2%) and the MBI was significantly less (average, 19.5+/-9.0 seconds vs. 56.5+/-38.9 seconds) among dry eye subjects compared with controls (p<0.05, Mann-Whitney U test). The DAGR was four times greater among dry eye subjects, who also showed significantly more tear breakup in the central cornea than controls (p<0.0001, Mann-Whitney U test). When the final image from three successive trials was overlapped, tear breakup occurred more often in the same location in three trials than would be expected by the overlap of independent points. CONCLUSIONS: Structural influences such as the "black line" or corneal lid defects appeared to influence the recurrence of breakup in the same region. The S-TBUD quantitative image analysis technique demonstrates that the tear film of subjects with dry eye continues to rapidly destabilize after an initial first break; thus, a low TBUT was combined with a high DAGR. The central corneal region of subjects with dry eye appeared especially susceptible to increased tear breakup when compared with controls.     

办公室干眼泪膜脂质层形态分析

目的应用Keeler泪膜镜评估办公室干眼泪膜脂质层形态的变化,并分析泪膜脂质层与其他干眼检测方法之间的相关性。方法横断面研究。本研究共纳入61例办公室工作人员（干眼患者33例,正常者28例）。所有受检者采用随机数字表法选择一眼按照以下顺序进行检查：干眼症状问卷表（OSDI）、泪新月容量、泪膜脂质层形态、非侵入性泪膜破裂时间、荧光素泪膜破裂时间、角膜荧光素染色以及Schirmer I试验。独立样本t检验或Mann-Whitney U检验用于比较2组间参数,Spearman相关用于分析脂质层厚度等级与其他参数的相关性。结果办公室干眼组脂质层[2（1~3）]较正常组[3（3~4）]薄（U=250,P<0.01）。在诊断办公室干眼时,脂质层厚度等级的最优诊断敏感性（0.545）和特异性（0.857）截断值为2级。脂质层厚度等级与非侵入性泪膜破裂时间和总泪新月容量呈正相关（r=0.485、0.349,P<0.05）,而与症状及其他检测方法不相关。结论Keeler泪膜镜可以有效评估办公室干眼泪膜脂质层厚度。泪膜脂质层厚度与泪新月容量、泪膜稳定性相关。     

A non-invasive instrument for clinical assessment of the pre-corneal tear film stability

A simple, non-invasive technique has been developed for assessment of the stability of the pre-corneal tear film. Changes are observed in the reflection of a grid pattern from the tear film surface. Breaks in the tear film appear as random discontinuities in the grid image. Using this non-invasive technique the stability of the pre-corneal tear film was assessed in nine normal subjects and twelve established dry-eye patients. The non-invasive tear film break-up time (NIBUT) of the dry-eye patients was on average only 25% to 32% of normal values. The non-invasive technique provides an alternative approach to diagnosing non-wetting disorders as well as a means of evaluating the efficacy of artificial tear solutions.     

Iris colour and the influence of local anaesthetics on pre-corneal tear film stability

Using non-invasive methods we report here that the stability of the pre-corneal tear film is lower in the brown eye than in the blue eye. The average stability in the blue eye is 15.8 sec (SD +/- 5.8) and in the brown eye it is 12.3 sec (SD +/- 2.9). On average, instillation of topical anaesthetics, benoxinate hydrochloride (0.4%) or amethacaine hydrochloride (0.5%), depress the stability of the pre-corneal tear film in blue eyes but not in brown eyes.     

PM2.5对小鼠泪膜功能和角膜上皮组织结构的影响

目的 观察PM2.5对小鼠泪膜功能和角膜上皮组织结构的影响.方法 24只雄性6～8周龄BALB/c小鼠,随机分为A、B两组,每组12只.B组采用5 mg·mL-PM2.5混悬液滴眼,A组采用PBS滴眼,每天4次.分别在干预后1d、4d、7d对各组小鼠进行泪膜功能检测,包括泪液分泌功能、泪膜破裂时间(break-up time,BUT)、荧光素染色(fluorescein staining,FL),并于干预后7d行苏木精-伊红染色观察角膜上皮情况.结果 干预后4d、7d,A组泪液分泌量、BUT较干预前无明显变化,差异均无统计学意义(均为P＞0.05),而B组泪液分泌量、BUT较干预前明显分别减少和恶化,差异均有统计学意义(均为P＜0.05).干预后7d,A组FL评分较干预前无明显变化,差异无统计学意义(P＞0.05),而B组FL评分较干预前明显增加,差异有统计学意义(P=0.003).干预后7d,A组上皮细胞层数为(4±1)层,而B组上皮细胞层数为(7±1)层,差异有统计学意义(P＜0.05).与A组比较,B组整个角膜FL着染明显增加,角膜表面上皮细胞层损伤,层数增厚.结论 PM2.5会影响小鼠泪膜功能,损伤小鼠角膜上皮的组织结构.     

Changes in ocular surface caused by antiglaucomatous eyedrops: prospective, randomised study for the comparison of 0.5% timolol v 0. 12% unoprostone

AIM: To study changes induced in ocular surface epithelia and the tear film by antiglaucomatous eyedrops. A beta blocker (0.5% timolol) and a novel prostaglandin F(2alpha) metabolite related drug (0.12% unoprostone) were examined in a prospective, randomised fashion. METHODS: 40 patients were randomly assigned to use either 0. 5% timolol (timolol group) or 0.12% unoprostone eyedrops (unoprostone group) twice a day for 24 weeks. In addition to routine ocular examinations, corneal epithelial integrity (vital staining tests, tear film break up time (BUT), anterior fluorometry, specular microscopy) and tear function (Schirmer's test, cotton thread test, tear clearance test (TCT)) were examined before and after the treatment. RESULTS: Both eyedrops caused significant reduction in intraocular pressure from the baseline levels. No significant changes were noted in corneal integrity in both groups, except a decrease in BUT at 20 weeks in the timolol group. The timolol group demonstrated significant decreases in Schirmer's test, tear clearance test, and tear function index (Schirmer's test value multiplied by clearance test); however, no such changes were noted in the unoprostone group. CONCLUSION: While unoprostone eyedrops caused no adverse effects on the corneal epithelial integrity and tear function, timolol caused significant impairments in tear production and turnover.