Double-masked, placebo-controlled safety and efficacy trial of diquafosol tetrasodium (INS365) ophthalmic solution for the treatment of dry eye

PURPOSE: To investigate the safety and efficacy of diquafosol tetrasodium, a P2Y2 receptor agonist that stimulates fluid and mucin secretion on the ocular surface, as a novel topical treatment of dry eye disease. METHODS: Subjects with dry eye (n=527) were evaluated in a randomized, double-masked, parallel-group trial comparing 24 weeks of treatment with 2 concentrations of diquafosol (1% and 2%) versus placebo instilled 4 times daily. Corneal staining, conjunctival staining, Schirmer tests, and subjective symptoms of dry eye were evaluated. Use of artificial tears was permitted as necessary. RESULTS: Subjects treated with 2% diquafosol had significantly lower corneal staining scores compared with placebo at the 6-week, primary efficacy time point (P<0.001), and superiority continued throughout the 24-week study. Reductions in corneal staining were observed as early as after 2 weeks of treatment, were maintained throughout the 24-week study, and were observed to worsen slightly (toward baseline) when diquafosol treatment was discontinued (week 25). Results for conjunctival staining were consistent with those observed for corneal staining. Schirmer scores at week 6 were significantly higher with diquafosol treatment than with placebo (P相似文献   

12-week study comparing the fixed combination of brimonidine and timolol with concomitant use of the individual components in patients with glaucoma and ocular hypertension

PURPOSE: To evaluate the efficacy and safety of fixed-combination brimonidine tartrate 0.2%/timolol 0.5% ophthalmic solution dosed BID and demonstrate non-inferiority to concomitant use of brimonidine tartrate 0.2% BID and timolol 0.5% BID in glaucoma and ocular hypertension patients with intraocular pressure (IOP) uncontrolled on monotherapy. METHODS: Randomized, multicenter, double-masked, parallel-group study involving 371 patients with inadequate IOP control (IOP from 22 to 34 mmHg) after > or =3 weeks of run-in on any monotherapy. Patients were treated with fixed-combination brimonidine/timolol BID (fixed-combination group, n = 188) or concomitant brimonidine BID and timolol BID (concomitant group, n = 183). IOP was assessed pre-dose and 2 hours after morning dosing at weeks 2, 6, and 12. RESULTS: A total of 355 patients (96%) completed the study. Patient demographics, run-in monotherapy, and baseline mean IOP on monotherapy were comparable between treatment groups. During follow-up, the mean reduction from baseline IOP was significant (p < 0.001) at all time points and ranged from 4.4 to 5.3 mmHg in each group. Brimonidine/timolol fixed combination was as effective as concomitant therapy with respect to mean IOP and mean change from baseline IOP at all time points and visits. Between-group differences were < or =0.35 mmHg for mean IOP and < or 0.30 mmHg for mean change from baseline IOP; none were significant. No unexpected side effects were associated with the fixed combination. Both treatments were well tolerated with no difference in adverse events between groups. CONCLUSIONS: Brimonidine/timolol fixed-combination therapy is as safe and effective as concomitant treatment with the individual components. Its simplified dosing regimen has the potential to improve compliance.     

Effects of topical anti-inflammatory agents in a botulinum toxin B-induced mouse model of keratoconjunctivitis sicca.

PURPOSE: The aim of this study was to compare the effects of topical nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid, doxycycline, and artificial tears for the treatment of ocular surface damage in the Botulinum toxin B (BTX-B)-induced mouse model of dry eye. METHODS: CBA/J mice were randomized into 2 experimental groups of 35 animals each. The control group received a transconjunctival injection of 0.05 mL of saline into the left lacrimal gland, and another group was injected with 0.05 mL of 20 milliunits BTX-B solution (SPSS, Inc., Chicago, IL). Three (3) days after intralacrimal gland injections, each group was equally randomized into 7 subgroups (n=5 each) to receive treatment unilaterally into their left eyes with topical artificial tears (0.5% carboxymethylcellulose sodium), 0.1% fluorometholone, 0.1% nepafenac, 0.4% ketorolac, 0.09% bromfenac, 0.1% diclofenac, or 0.025% doxycycline. Tear volume, ocular surface changes, and spontaneous blink rate were evaluated in each of the 14 experimental subgroups. RESULTS: Topical fluorometholone, nepafenac, and doxycycline significantly improved corneal surface staining in the BTX-B-injected mice within 2 weeks of treatment. Topical ketorolac, diclofenac, and bromfenac, applied twice-daily, partially reduce corneal staining, and did so more slowly by the 4-week time point. In comparison, topical artificial tear-treated mice did not demonstrate significant improvement of the corneal surface at any time point. Aqueous tear production in the BTX-B-injected fluorometholone-treated group started to return to baseline level within 2 weeks, although not significantly. Meanwhile, BTX-B-injected mice treated with artificial tears, topical NSAIDs, and doxycycline still exhibited a reduction in tear production up to 4 weeks. No significant differences in blink rate between the control and study groups undergoing the various treatments were noted at all time points. CONCLUSIONS: This study suggests the potential usefulness of topical NSAIDs, corticosteroid, and doxycycline for the clinical treatment of ocular surface epithelial disorders associated with dry eye.     

Exposure to a dry environment induces strain-specific responses in mice

Most current animal models of dry eye have a single causative mechanism and do not take into consideration the influence of environmental conditions on tear secretion and associated ocular surface signs. Since immunity and inflammation have been implicated in dry eye pathogenesis, and different mouse strains are known to have differentially biased immune responses, we conducted the present study to test the hypothesis that strains with specifically polarized T cell responses (T helper-1 [Th1] vs. T helper-2 [Th2]) develop differential signs of dry eye when exposed to a controlled low humidity setting. Eight to 12-week-old BALB/c (Th2 biased) and C57BL/6 (Th1 biased) mice were placed in a controlled environment chamber (CEC) where relative humidity (RH), temperature (T), and air flow (AF) were continuously regulated and monitored. Mice were exposed to specific environmental controlled conditions (RH=15.5+/-3.8%, AF=15 l/min, T=21-23 degrees C) for 3 to 7 days. Aqueous tear production by means of the cotton thread test, corneal fluorescein staining (NEI grading scheme, score 0-15) and goblet cell density in the superior and inferior conjunctivae were measured by a masked observer. No statistically significant differences between the groups were found at baseline. Statistically significant decreases in tear secretion were seen after exposure to the CEC environment. Mean cotton thread wetting was 1.9+/-0.2 (baseline), 1.4+/-0.3 (day 3), and 0.9+/-0.2 mm (day 7) for BALB/c mice, and 1.7+/-0.3 (baseline), 0.9+/-0.3 (day 3), and 0.4+/-0.2 mm (day 7) for C57BL/6 mice. These mice showed reduced tear secretion as compared to BALB/C at each time point tested (P<.005, t-test). Both BALB/c and C57BL/6 mice showed a significant increase in corneal fluorescein staining at both day 3 and day 7 as compared to baseline. With exposure to the CEC goblet cell density significantly decreased in the superior and inferior conjunctivae in BALB/c mice, while it remained unchanged in C57BL/6 mice. This study indicates that exposure of non-pharmacologically modified mice to a low humidity environment in the CEC can lead to significant alterations in tear secretion, goblet cell density, and acquisition of dry eye-related ocular surface signs which are strain-specific.     

Corneal punctate staining with latanoprost, bimatoprost, and travoprost in healthy subjects

PURPOSE: To evaluate short-term conjunctival and corneal punctate staining with latanoprost, bimatoprost, and travoprost in healthy individuals. MATERIALS AND METHODS: A single centered, active-controlled, three-period crossover comparison that evaluated conjunctival and corneal punctate staining, by grade and individual stains, in healthy subjects after dosing for five days in one eye with latanoprost, bimatoprost, or travoprost. Staining was evaluated at 24-hour trough (Hour 0) and at Hour 1 after dosing. RESULTS: Twenty-eight subjects completed this study. This study found that there was no significant difference by ANOVA for the number of individual corneal punctate stains either at trough (latanoprost 22.6 +/- 25.4, bimatoprost 16.8 +/- 25.6, and travoprost 21.1 +/- 26.0 mm Hg) (P = 0.33) or at 1 hour after dosing (latanoprost 23.8 +/- 26.3 bimatoprost 18.2 +/- 25.2, and travoprost 26.1 +/- 26.1 mm Hg) (P = 0.75) among treatment groups. No significant differences existed among treatment groups in the study eye compared with the non-study eye or to the study eye at Hour 0 or Hour 1 or to the period initiation or baseline visits (P > 0.05). Several significantly different comparisons, inconsistent in nature, were observed for the nasal and temporal conjunctival staining between the treatment groups. There were no differences in unsolicited or solicited adverse events between groups. CONCLUSION: This study suggests that, in healthy subjects after short-term treatment, latanoprost, bimatoprost, and travoprost demonstrate generally similar ocular surface epithelial staining characteristics.     

Assessing the severity of keratitis sicca with videokeratoscopic indices

PURPOSE: To determine the correlation between the regularity indices of the Tomey TMS-2N computerized videokeratoscopy (CVK) instrument (Tomey, Waltham, MA) with conventional measures of dry eye symptoms and disease. DESIGN: A retrospective, clinic-based, case-control study. PARTICIPANTS: A total of 16 eyes of 16 asymptomatic normal subjects and 74 eyes of 74 patients with reports of ocular irritation. METHODS: Corneal surface regularity and potential visual acuity indices of the Tomey TMS-2N CVK instrument were evaluated in patients with ocular irritation symptoms and in normal subjects. MAIN OUTCOME MEASURES: The surface regularity index (SRI), surface asymmetry index (SAI), potential visual acuity index (PVA), and irregular astigmatism index (IAI) of the Tomey TMS-2N were compared between normal and dry-eye patients. Severity of dry-eye symptoms was assessed with a validated questionnaire. Schirmer 1 test (without anesthesia), biomicroscopic meibomian gland evaluation with a composite severity score (MGD score), fluorescein tear break-up time (TBUT), and corneal fluorescein staining were performed. The correlations between CVK indices of the Tomey TMS-2N and the symptom severity score, Schirmer 1 test, MGD score, TBUT, and corneal fluorescein staining score were studied. RESULTS: Dry-eye patients had greater mean symptom severity scores, lower Schirmer 1 test scores, greater MGD scores, more rapid TBUT, and greater total corneal fluorescein staining scores (P < 0.001 for all parameters). The SRI, SAI, and IAI were all significantly greater in dry-eye patients than normal subjects. These were 0.46 +/- 0.36 (normal) versus 1.09 +/- 0.76 (dry) for the SRI (P = 0.0017), 0.30 +/- 0.15 (normal) versus 0.90 +/- 1.09 (dry) for the SAI (P = 0.0321), and 0.42 +/- 0.28 (normal) versus 0.56 +/- 0.24 (dry) for the IAI (P = 0.0321). The PVA index was significantly lower in the dry-eye patients (0.89 +/- 0.13) than normal eyes (0.68 +/- 0.23; P = 0.0008). The SRI, SAI, and IAI were positively correlated with total and central corneal fluorescein staining scores (P < 0.00001 for all indices). An SRI (> or =0.80), SAI (> or =0.50), and IAI (> or =0.50) had sensitivities in predicting total corneal fluorescein staining (score > or = 3) of 89%, 69%, and 82%, respectively. The specificity of these indices was 80%, 78%, and 82%, respectively. In all 90 eyes, the mean SRI was greater in subjects older than 50 years (P = 0.012) compared with younger patients, whereas no age effect was noted in the dry-eye patients. The SRI and PVA index showed better correlation with symptoms of blurred vision than the best-corrected visual acuity. CONCLUSIONS: Patients with ocular irritation have an irregular corneal surface that may contribute to their irritation and visual symptoms. Because of their high sensitivity and specificity, the regularity indices of the Tomey TMS-2N have the potential to be used as objective diagnostic indices for dry eye, as well as a means to evaluate the severity of this disease.     

Effects of lacrimal occlusion with collagen and silicone plugs on patients with conjunctivitis associated with dry eye

PURPOSE: To determine whether canalicular occlusion with collagen and silicone plugs reduces the severity of symptoms in patients with conjunctivitis secondary to dry eye. METHODS: This was a prospective, randomized, double-masked study conducted at a single center in Mexico, in which 61 patients with dry eye/conjunctivitis were assigned to progressive lacrimal occlusion with collagen and silicone plugs or a sham procedural group. Outcome variables included total and individual dry eye and conjunctivitis symptom scores, moisturizing agent usage, best-corrected visual acuity, ocular comfort level, visual performance, corneal/conjunctival fluorescein staining, and incidence of adverse events. RESULTS: Total dry eye and conjunctival symptom scores were reduced by 43.7 and 33.7%, respectively 2 weeks after occlusion of all four lacrimal canaliculi with collagen plugs, increasing to 77.4 and 72.1% 2 weeks later following superior canalicular occlusion of both eyes with silicone plugs and inferior placement of collagen plugs. At the 8-week visit (4 weeks after silicone plug implantation of the inferior canaliculi of both eyes), the reduction in total dry eye and conjunctival symptom scores further increased to 94.2 and 93.0%, respectively, accompanied by a marked decline in each of the seven individual symptom scores (dryness, watery eyes, itching, burning, foreign body, fluctuating vision, and light sensitivity). In concert with these changes, moisturizing agent usage and corneal/conjunctival fluorescein staining decreased in a progressive fashion over the 8-week study period, and best-corrected visual acuity, ocular comfort, and visual performance improved in the absence of any treatment-related adverse events except for one case of epiphora. The response of patients to lacrimal occlusion can be sharply contrasted with the sham procedure group, which remained relatively unchanged from baseline at each of the study visits. CONCLUSIONS: Progressive lacrimal occlusion with collagen and silicone plugs was of clinical benefit to patients with dry eye and conjunctivitis.     

Interleukin-6 and tumor necrosis factor-alpha levels in tears of patients with dry eye syndrome

PURPOSE: To determine the levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in tears of patients with dry eye syndrome. METHODS: IL-6 and TNF-alpha levels were measured by enzyme-linked immunosorbent assay in tear samples obtained from 18 patients with dry eye (8 patients with Sj?gren syndrome and 10 patients with non-Sj?gren syndrome) and 14 control subjects. The correlation between IL-6 and TNF-alpha levels and tear film and ocular surface parameters was analyzed. The relative expression of these cytokines was evaluated in conjunctival impression cytology and conjunctival biopsy specimens by using immunohistochemical staining. RESULTS: The mean levels of IL-6 and TNF-alpha were, respectively, 18.57 +/- 8.92 and 3.68 +/- 3.45 pg/mL in patients with dry eye and 3.59 +/- 3.38 (P < 0.01) and < 0.5 (P < 0.01) pg/mL in control subjects. IL-6 level was significantly increased in tears of patients with Sj?gren syndrome compared with those with non-Sj?gren syndrome (P < 0.01). IL-6 level correlated significantly with tear film breakup time (P = 0.04), Schirmer test (P < 0.01), tear clearance (P = 0.02), keratoepithelioplasty score (P < 0.01), and goblet cell density (P = 0.03), but not with corneal sensitivity (P = 0.08). There was no significant difference in TNF-alpha level between patients with non-Sj?gren and Sj?gren syndrome. TNF-alpha levels did not correlate with tear film and ocular surface parameters. Immunohistochemical staining showed positive staining for IL-6 in specimens from patients with dry eye, especially in specimens from patients with Sj?gren syndrome. CONCLUSION: IL-6 and TNF-alpha levels are elevated in tears of patients with dry eye syndrome. IL-6 level, but not TNF-alpha level, is associated with the severity of the disease and correlates with various tear film and ocular surface parameters.     

非加热型湿房镜治疗干眼的临床疗效

目的评价湿房镜治疗干眼的临床疗效。方法自身对照临床研究。连续收集2012年11月至2013年6月期间在门诊就诊的轻中度干眼患者56例（56眼）,填写干眼症状问卷、眼表疾病指数量表（OSDI）问卷,并进行眨眼频次、结膜充血程度、角膜荧光染色及泪液分泌试验（SIT）和泪膜破裂时间（BUT）测定。予配戴湿房镜1周后再次检查,内容同上。采用自身对照的配对t检验或秩和检验对治疗前后的数据进行统计学分析,并用秩和相关检验方法分析眼表保护指数（OPI）与角膜荧光染色的相关性。结果56例干眼患者配戴湿房镜1周后,干眼症状明显改善,其中干眼问卷评分（Z=-5.084,P＜0.01）及OSDI问卷评分（Z=-5.149,P＜0.01）较治疗前改善,差异有统计学意义;眨眼频次减少（t=6.430,P<0.01）;睑结膜充血（Z=-4.185,P＜0.01）、球结膜充血（Z=-2.598,P＜0.01）、角膜荧光染色（Z=-5.001,P＜0.01）及体征总分（Z=-5.288,P＜0.01）等临床体征评分明显降低,差异均有统计学意义;BUT明显增加（t=7.416,P<0.01）,OPI明显增加（Z=-5.622,P＜0.01）,差异具统计学意义。OPI指数与角膜荧光染色评分呈负相关（r=-0.445,P＜0.01）。结论湿房镜可有效缓解轻中度干眼患者主观症状,稳定泪膜,减轻临床体征,是干眼的有效治疗手段之一。     

Comparison of topical cyclosporine, punctal occlusion, and a combination for the treatment of dry eye

PURPOSE: To compare the efficacy of topical cyclosporine, punctal occlusion, and a combination for the treatment of dry eye. METHODS: Patients with dry eye (N = 30) seen in a university-affiliated private practice were randomized to 1 of 3 treatments: cyclosporine 0.05% ophthalmic emulsion (RESTASIS) twice daily, lower-lid punctal plugs (PARASOL), or a plugs-cyclosporine combination. Tear volume, ocular surface staining, and artificial tear use were assessed at baseline and 1, 3, and 6 months. RESULTS: All treatments improved Schirmer scores by 6 months (P < or = 0.005 vs. baseline), with plug-containing regimens favored at 1 and 3 months (P < 0.001 vs. cyclosporine alone). Cyclosporine-containing regimens, but not plugs alone, improved rose bengal staining at 3 and 6 months (P < or = 0.010 vs. baseline). Artificial tear use decreased with plug-containing regimens at 1 month and with all treatments at 3 and 6 months (P < or = 0.005 vs. baseline). Combination therapy produced the greatest overall improvements and was superior to plugs alone in decreasing artificial tear use at 6 months (P = 0.012). CONCLUSIONS: All 3 regimens effectively treated dry eye. Plug-containing regimens increased wetness initially; cyclosporine appeared to promote long-term ocular surface health. The effects may be additive. Patients with punctal occlusion may benefit from adjunctive cyclosporine.     

Evaluation of Dry Eye after Minimal in Situ Conjunctival Incision for Segmental Scleral Buckling Surgery

Objective: To compare dry eye signs and symptoms after minimal in situ conjunctival incision for segmental scleral buckling surgery. Methods: In this prospective clinical study, consecutive patients, enrolled in the Department of Ophthalmology, the First Affiliated Hospital of Xi'an Jiaotong University, from May 2015 to April 2017, who had minimal in situ conjunctival incision or standard segmental scleral buckling surgery were assessed. Dry eye markers including the ocular surface disease index (OSDI) and subjective symptom questionnaire, tear-film assessment using Keratograph 5M corneal topography, Schirmer Ⅰ testing, and fluorescein staining were sequentially evaluated preoperatively and at 1 day, 1 week, and 1 month postoperatively. A Chi-square test, Student's t-test or Mann-Whitney U test was used to compare differences between the two groups. Results: Seventy-eight patients (78 eyes) with similar baseline characteristics were recruited. Most patients developed dry eye postoperatively. Subjective symptoms and fluorescein staining scores elevated from baseline, tear break-up time and Schirmer Ⅰ testing values decreased postoperatively, which peaked at 1 day and did not return to baseline within 1 month. There were no significant differences between the 2 groups (all P>0.05) at 1 day and 1 week except for the higher tear meniscus height (Z=1.04, P=0.041), noninvasive first tear break-up time and average break-up time (t=2.51, P<0.001), and Schirmer Ⅰ test values (Z=2.34, P=0.043), in the minimal in situ conjunctival incision group at 1 month postoperatively. OSDI scores and subjective symptoms were lower in the minimal in situ conjunctival incision group at 1 week and 1 month postoperatively (OSDI: t1 week=2.54, P=0.012; Z1 month=-1.03, P=0.020; subjective symptoms: t1 week=3.04, P=0.011; t1 month=3.94, P<0.001). Sub group analysis using flouesecein staining showed obvious worsening 1 day, 1 week and 1 month postoperatively in patients with preoperative dry eye (Z=-2.42, P<0.001; Z=-1.54, P=0.034; Z=-1.83, P=0.041). Conclusions: Segmental scleral buckling surgery can induce or aggravate dry eyes. Compared with standard procedures, minimal in situ conjunctival incision segmental scleral buckling surgery can improve and shorten the ocular surface discomfort in the early postoperative period, especially in patients with dry eyes before surgery.     

Correlation between corneal sensitivity, subjective dry eye symptoms and corneal staining in Sjögren's syndrome

BACKGROUND: Previous studies have shown a poor correlation between dry eye symptoms and objective clinical signs in patients with Sj?gren's syndrome.We examined the hypothesis that reduced corneal sensitivity is associated with increased ocular surface disease and reduced symptoms in patients with Sj?gren's syndrome. METHODS: Eighteen subjects with a diagnosis of Sj?gren's syndrome attending a Sj?gren's clinic participated in the study. All participants completed the Ocular Surface Disease Index (OSDI) and the Symptom Severity of Discomfort (SSD) scale and answered a question regarding overall severity of dry eye symptoms.The subjects underwent measurement of best-corrected Snellen visual acuity, corneal sensitivity testing with the Cochet-Bonnet esthesiometer, fluorescein and lissamine green staining of the cornea, Schirmer's test I and determination of the tear film break-up time.The results were analysed using Pearson correlational analysis. RESULTS: Both fluorescein and lissamine green staining of the cornea correlated negatively with central corneal sensation (r = -0.3542, p = 0.034, and r = -0.3748, p = 0.029 respectively), indicating that corneal sensation was reduced with increased ocular surface disease. The overall symptom severity correlated negatively with lissamine green staining of the cornea (r = -0.4310, p = 0.011), suggesting reduced symptoms with increased corneal disease. INTERPRETATION: Reduced corneal sensation correlated with increased ocular surface disease. Ocular surface disease similarly demonstrated a reciprocal relation with patients' dry eye symptoms. Consequently, we found that patients with Sjogren's syndrome with advanced corneal staining tended to have fewer dry eye symptoms than patients with less corneal staining.     

Effect of topical olopatadine and epinastine in the botulinum toxin B-induced mouse model of dry eye.

PURPOSE: The aim of this study was to compare the effect of topical olopatadine, epinastine, and lubricant eye drops on dry eye ocular surface disease in the botulinum toxin B (BTX-B)-induced mouse model of keratoconjunctivitis sicca. METHODS: CBA/J mice were randomized into 3 experimental groups of 10 animals each. All mice received a transconjunctival injection of 0.05 mL of 20-mU BTX-B solutions into the left lacrimal gland. Three (3) days after intralacrimal gland injections, each group received treatment with twice-daily topical lubricant as a control, 0.1% olopatadine, or 0.05% epinastine eye drops. To monitor the progression of dry eye tear production, an ocular surface fluorescein staining score was evaluated in each of the 3 experimental groups. RESULTS: Three (3) days after the intralacrimal gland injection of BTX-B, aqueous tear production was significantly decreased (1.95+/-0.64 mm), compared to baseline level (2.69+/-0.66 mm; P<0.001). Similarly, there was a statistically significant increase in the proportion of mice with a corneal staining score of 2 or greater at 3 days postinjection, compared to the preinjection value (P<0.001). There were no statistically significant differences in aqueous tear production between the 3 different medication groups at all time points. Aqueous tear production in neither the olopatadine nor the epinastine-challenged groups was further decreased compared to the lubricant-treated group. Difference in the proportion of mice with a low- and high corneal staining score between the control and study groups did not reach statistical significance throughout the 4-week experimental period. In addition, changes in corneal fluorescein staining of the olopatadine group versus the epinastine group did not show a statistically significant difference. CONCLUSIONS: Topical olopatadine and epinastine do not cause significantly additional damage to the compromised ocular surface secondary to dry eye after continuous 4-week, twice-daily application. Topical olopatadine and epinastine appear to have comparable effects on aqueous tear-production and corneal-surface changes in this mouse model.     

Dry eye after LASIK: Comparison of outcomes for Asian and Caucasian eyes

Background : Dry eye is a common complication of LASIK surgery. Our clinical impression was that post‐LASIK dry eye was more problematic for our Asian patients. The aim of this study was to determine if dry eye after LASIK is more prevalent, more sustained and more severe in Asian eyes compared with Caucasian eyes. Methods : This study was based on a retrospective analysis of a clinical database. Data (n = 932 eyes, 932 patients) was collected before and after (week 2 and months 1, 3 and 6) LASIK surgery. Patients were defined as Asian if both parents were of East Asian ethic origin. Assessments included dry eye symptoms, ocular surface staining, tear volume, tear secretion, tear film stability and corneal sensation. Results : Asian eyes had greater ocular surface staining, poorer tear film stability and lower tear volume before LASIK and at all times after LASIK. Dry eye symptoms occurring ‘often or constantly’ were more prevalent at all time points after LASIK in Asian eyes. Chronic dry eye persisting six months or more after LASIK was diagnosed in 28 per cent of Asian eyes and 5 per cent of Caucasian eyes (p < 0.001). Asian patients with chronic dry eye were predominantly female, reported dry eye symptoms, had greater ocular surface staining and lower tear secretion, stability and volume before surgery. After LASIK, Asian eyes had a slower return to pre‐operative values for ocular surface staining, tear volume and corneal sensation. Discussion : The risk of chronic dry eye after LASIK was significantly higher in Asian eyes. Contributing factors could include racial differences in eyelid and orbital anatomy, tear film parameters and blinking dynamics and higher attempted refractive corrections in Asian eyes.     

Lid scrubbing with a gel combining natural extracts for dry eye treatment

AIM: To evaluate the effect of lid scrubbing using a gel combining different natural extracts on ocular signs and symptoms of dry eye patients. METHODS: A retrospective study was performed on 19 dry eye patients (51.1±16.0y). Non-invasive tear break-up time, tear meniscus height, meibomian gland loss, lipid layer thickness, conjunctival redness, corneal staining, ocular surface disease index (OSDI), and ocular pain intensity were measured before (baseline), 1wk, and 2mo after lid scrubbing with a gel containing different natural extracts (okra extract, aloe vera leaf juice, hydrolysed soy protein, caffeine, citrus unshiu peel extract, and raspberry seed oil). RESULTS: Compared with the baseline, there was a statistically significant improvement in both first (P=0.048) and average (P=0.026) non-invasive tear break-up time 2mo after treatment, as well as in corneal staining (P=0.043, 0.012), OSDI (P<0.001), and ocular pain intensity (P<0.001) after 1wk and 2mo. In addition, there was no correlation between ocular signs and symptoms. CONCLUSION: The lid scrubbing with a gel combining different natural extracts show beneficial effects on tear film stability, corneal damage, and ocular symptoms, which is the reason why this therapeutic procedure is proposed as an alternative for dry eye management. However, it is not possible to attribute this beneficial effect solely to the presence of the natural extracts in the gel, primarily due to the absence of a negative control group.     

A murine model of dry eye induced by an intelligently controlled environmental system

PURPOSE: To establish a novel murine model of dry eye using an intelligently controlled environmental system (ICES). METHODS: Thirty BALB/c mice aged 4 to 6 weeks were housed in the ICES in which the relative humidity, airflow, and temperature were maintained at 15.3% +/- 3% (mean +/- SD), 2.1 +/- 0.2 m/s, and 21 degrees to 23 degrees C, respectively, for 42 days. Thirty mice of similar age and housed in a normal environment were controls (relative humidity, 60%-80%; no airflow; temperature, 21 degrees -23 degrees C). The ocular surfaces of the animals in both groups were analyzed before and 3, 7, 14, 28, and 42 days after the experiment for aqueous tear production, corneal barrier function, conjunctival morphology, and goblet cell density. The level of apoptosis on the ocular surface also was assessed using active caspase-3 at 42 days. RESULTS: A low-humidity environment was maintained constantly by the ICES. Animals in this environment had decreased aqueous tear production, increased corneal fluorescein staining, and marked thinning and accelerated desquamation of the apical corneal epithelium compared with control eyes. Squamous metaplasia of the conjunctival epithelium with decreased goblet cell density also developed in the animals housed in the ICES. Active caspase-3 was highly expressed on the ocular surfaces of the animals housed in the ICES at 42 days. CONCLUSIONS: The biological and morphologic changes of dry eye induced by ICES in mice are similar to those in humans. This dry eye environment appears to upregulate apoptosis on the ocular surface.     

Double-masked comparison of ketorolac tromethamine 0.4% versus nepafenac sodium 0.1% for postoperative healing rates and pain control in eyes undergoing surface ablation

PURPOSE: Determine the degree of postoperative pain and rate of healing in eyes treated with either ketorolac tromethamine 0.4% (Acular LS) or nepafenac sodium 0.1% (Nevanac) after flapless surface ablation [epi-laser in situ keratomileusis (LASIK)]. METHODS: Prospective, randomized, double-masked, paired-eye comparison. Patients undergoing flapless surface ablation were randomized to receive ketorolac in 1 eye and nepafenac in the other. Drops were instilled immediately after the surgical procedure, and patients continued to instill the masked drops 3 times daily for 5 days. Study follow-up visits were at days 1 and 5 postoperatively. Patients were queried by phone regarding their level of pain at 5 hours postoperatively and on days 2, 3, and 4. Outcome measures included postoperative pain levels including need for additional rescue medications, rate of healing, and adverse events. RESULTS: Although the original target population was 60 eyes of 30 patients, this study was halted after only 14 eyes of 7 patients because of concern for patient safety, because most patients in 1 arm developed haze. Eyes treated with nepafenac healed at a slower rate than eyes treated with ketorolac in 57% of patients. Mean time to healing was 5.7 +/- 1.1 days with ketorolac and 7.9 +/- 2.1 days with nepafenac (P = 0.066). Moreover, eyes treated with nepafenac exhibited statistically significant greater mean hazing scores at week 2 (P = 0.024) and month 1 (P = 0.039). Throughout the study, a greater percentage of nepafenac-treated eyes exhibited haze than did ketorolac-treated eyes. This difference was statistically significant at week 2 (P = 0.005) and month 1 (P = 0.039). Patients reported significantly more pain in nepafenac-treated eyes at day 3 when pain was at its peak (P = 0.046). CONCLUSIONS: In patients undergoing epi-LASIK, a statistically significant trend postoperative toward increased corneal haze was seen with nepafenac compared with ketorolac. Nepafenac therapy resulted in a non-statistically significant trend toward delayed healing. The study was halted because of safety concerns.     

The effect of hinge position on corneal sensation and dry eye after LASIK

PURPOSE: To investigate the effect of hinge position on corneal sensation and dry eye syndrome after laser in situ keratomileusis (LASIK). DESIGN: Prospective, randomized, self-controlled trial. PARTICIPANTS: Fifty-two patients >/=18 years of age undergoing bilateral LASIK. INTERVENTION: Patients underwent bilateral LASIK with the superior-hinge Hansatome microkeratome in one eye and the nasal-hinge Amadeus microkeratome in the other eye. In all eyes, the flaps were 160 micro m thick, with a diameter of 9.5 mm. MAIN OUTCOME MEASURES: Masked Cochet-Bonnet esthesiometry was performed centrally before surgery and at 1 week, 1 month, 3 months, and 6 months after surgery. Dry eye was evaluated at the same time intervals with lissamine green corneal and conjunctival staining, Schirmer testing with anesthesia, and tear-film breakup time. Subjective evaluation of dry eye sensation was performed at 3 and 6 months after surgery. RESULTS: Corneal sensation was reduced in eyes with either superior- or nasal-hinge corneal flaps at 1 week, 1 month, and 3 months after surgery (P < 0.001). Compared with preoperative values, a significant reduction in corneal sensation remained at 6 months in corneas with superior-hinge flaps (P < 0.001) but not in corneas with nasal-hinge flaps (P = 0.263). Mean corneal sensation was greater in corneas with a nasal-hinge flap compared with corneas with a superior-hinge flap at all postoperative visits (P < 0.001). The loss of sensation was greatest at 1 week and showed improvement at each subsequent time interval up to 6 months. Overall, dry eye signs and symptoms were greatest during the immediate postoperative period and improved at all subsequent time intervals. Dry eye signs and symptoms were generally greatest in the eyes with a superior-hinge flap and milder in eyes with a nasal-hinge flap. CONCLUSIONS: The long posterior corneal nerves, which innervate the cornea, enter the eye at 3- and 9-o'clock. A superior-hinge flap transects both arms of the neuroplexus, whereas a nasal hinge transects only the temporal arm. LASIK results in a significant reduction in corneal sensation. Corneal sensation and dry eye signs and symptoms decreased immediately after LASIK and improved at all time periods between 1 week and 6 months in eyes with both a nasal-hinge flap and a superior-hinge flap. However, the loss of corneal sensation and presence of dry eye syndrome were greater in eyes with a superior-hinge flap than in eyes with a nasal-hinge flap.     

A 3-month comparison of efficacy and safety of brimonidine-purite 0.15% and brimonidine 0.2% in patients with glaucoma or ocular hypertension.

PURPOSE: To compare the efficacy and safety of brimonidine Purite 0.15% (ALPHAGAN P) BID with brimonidine 0.2% (ALPHAGAN) BID in patients with glaucoma or ocular hypertension. METHODS: 3-month, multicenter, randomized, double-masked trial. Eligible patients were taking brimonidine 0.2% BID for at least 6 weeks prior to study entry and their intraocular pressure (IOP) was < or = 21 mm Hg. Patients were randomly assigned to receive either brimonidine Purite 0.15% BID (n = 203) or brimonidine 0.2% BID (n = 204). Scheduled visits were prestudy, baseline, and weeks 2, 6 and 12. IOP was measured at hour 0 and hour 2 to evaluate efficacy. Safety was measured by monitoring adverse events. Patient satisfaction and comfort were also evaluated at all visits. RESULTS: There was no statistically significant difference between the brimonidine 0.2% and brimonidine Purite 0.15% groups with respect to mean IOP at baseline. The IOP-lowering efficacy of brimonidine Purite 0.15% was equivalent to that of brimonidine 0.2% and both study treatments maintained IOP-lowering effects of brimonidine 0.2%. There were no significant between-group differences in mean IOP. The differences in the mean IOPs were < or = 0.26 mm Hg and the mean change from baseline IOP was < or = 0.35 mm Hg at all follow-up time points. There were no statistically significant differences between the two groups in the overall incidence of adverse events. The most commonly reported treatment-related adverse events were conjunctival hyperemia and allergic conjunctivitis: both were mild in severity. CONCLUSION: Brimonidine Purite 0.15% dosed BID provides equal IOP-lowering efficacy to brimonidine 0.2% BID. Patients previously controlled on brimonidine 0.2% can be successfully switched to brimonidine Purite 0.15%.     

不同浓度人血清滴眼液治疗重症干眼大鼠的实验研究

目的 探讨不同浓度人血清滴眼液在重症干眼大鼠中的治疗效果.设计实验研究.研究对象 Sprague-Dawley （SD）大鼠28只.方法 28只健康成年雄性SD大鼠,随机分为正常对照组（n=4）,重症干眼组（n=24）,使用0.2%苯扎氯铵溶液点眼1周制作重症干眼模型.然后将重症干眼大鼠随机分为阴性对照组（n=6）,20%血清组（n=6）,50%血清组（n=6）,100%血清组（n=6）,使用相应浓度的血清滴眼液治疗28天,观察各组大鼠在制模后第0、7、14、21、28天的泪液分泌情况和眼表的改变.主要指标应用Schirmer试验、角膜荧光素染色、结膜印迹细胞学检查干眼程度.结果 重症干眼组与正常组大鼠各观察指标的差异有统计学意义,其中Schirmer试验（2.12±1.50 mm vs 8.67±2.36 mm,P=0.000）,角膜荧光素染色分级（4.0 vs 0.33±0.58,P=0.008）.结膜印迹细胞学分级（1.76±0.52 vs 0.33±0.58,P=0.000）.20%血清组大鼠较阴性对照组在第7、21天泪液分泌增ta（P=0.003,0.035）;第7、14、21、28天角膜荧光素染色减轻（P=0.001,0.006,0.021,0.001）;第14、21、28天印迹细胞学分级减轻（P=0.015,0.002,0.01）. 50%血清组较阴性对照组在第7、14、28天角膜荧光素染色减轻（P=0.025,0.023,0.004）;第14天印迹细胞学分级减轻（P=0.046）. 100%血清组较阴性对照组在第28天角膜荧光素染色减轻（P=0.021）,余差异无统计学意义（P〉0.05）.结论 不同浓度人血清滴眼液均有助于重症干眼大鼠角膜上皮的修复,其中20%的人血清滴眼液效果最理想,可以增加泪液分泌,减轻结膜和角膜上皮的损害.