Bevacizumab in High-Risk Corneal Transplantation: A Pilot Multicenter Prospective Randomized Control Trial.

PURPOSE: To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin) treatment in patients undergoing vascularized high-risk corneal transplantation. DESIGN: Pilot, prospective, randomized, double-blind, placebo-controlled clinical trial conducted at 5 clinical centers in the United States, India, and Brazil. PARTICIPANTS: Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft. METHODS: Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks. MAIN OUTCOME MEASURE: The 52-week endothelial immune rejection rate. RESULTS: Ninety-two patients were randomized to receive bevacizumab (n = 48) or control (n = 44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (P = 0.20). Post hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (P = 0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65, P = 0.01) in a post hoc Cox regression analysis. CONCLUSIONS: In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection.

The Early Effects of Alcohol Consumption on Functional Visual Acuity, Tear Functions, and the Ocular Surface.

PURPOSE: We investigated the early effects of alcohol intake on tear functions and ocular surface health in this prospective controlled study. METHODS: Forty-four eyes of 22 subjects (17 males, 5 females; mean age: 35.3 years) who drank 200 mL of 25% Japanese vodka and 44 eyes of age- and sex-matched 22 control subjects who drank water were investigated. Subjects were requested to refrain from alcohol consumption from the previous day and food ingestion 6 hr before the study. Each subject consumed exactly the same order prepared dinner and same quantity of alcohol over the same time frame. Subjects underwent breath alcohol level, tear evaporation and blink rate, tear lipid layer interferometry, tear film break-up time (BUT), fluorescein and Rose Bengal stainings, Schirmer test, and visual analog scale (VAS) evaluation of dry eye symptoms before, as well as 2 and 12 hr after alcohol intake. RESULTS: The mean breath alcohol level was significantly higher in the alcohol group compared to the water group at 2 and 12 hr (P<0.001). The mean tear evaporation increased significantly from 2.5×10-7 to 8.8×10-7 gr/cm2/sec 12 hr after alcohol intake (P<0.001). The mean BUT shortened significantly from 15.0±5.0 to 5.0±2.5 sec 12 hr after alcohol intake. Lipid layer interferometry showed signs of tear film thinning 12 hr after alcohol intake in all subjects of the alcohol intake group, which was not observed in the water group. The mean blink rates increased significantly from 10.6±1.5 blinks/min to 13.5±0.9 blinks/min and 15.1±1.2 blinks/min at 2 and 12 hr, respectively, in the alcohol group (P<0.001). The Schirmer test values decreased significantly 12 hr after alcohol intake (P<0.001). The mean VAS score for dryness increased from baseline significantly in the alcohol group at 12 hr (P<0.001). No significant time-wise changes in tear functions were observed in the water group. CONCLUSION: The tear film and ocular surface epithelia showed early and distinctive quantitative and qualitative changes associated with visual disturbances after alcohol intake.

IKZF1, a new susceptibility gene for cold medicine-related Stevens-Johnson syndrome/toxic epidermal necrolysis with severe mucosal involvement.

BACKGROUND: Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN), are acute inflammatory vesiculobullous reactions of the skin and mucous membranes, including the ocular surface, oral cavity, and genitals. These reactions are very rare but are often associated with inciting drugs, infectious agents, or both. OBJECTIVE: We sought to identify susceptibility loci for cold medicine-related SJS/TEN (CM-SJS/TEN) with severe mucosal involvement (SMI). METHODS: A genome-wide association study was performed in 808 Japanese subjects (117 patients with CM-SJS/TEN with SMI and 691 healthy control subjects), and subsequent replication studies were performed in 204 other Japanese subjects (16 cases and 188 control subjects), 117 Korean subjects (27 cases and 90 control subjects), 76 Indian subjects (20 cases and 56 control subjects), and 174 Brazilian subjects (39 cases and 135 control subjects). RESULTS: In addition to the most significant susceptibility region, HLA-A, we identified IKZF1, which encodes Ikaros, as a novel susceptibility gene (meta-analysis, rs4917014 [G vs. T]; odds ratio, 0.5; P = 8.5 × 10(-11)). Furthermore, quantitative ratios of the IKZF1 alternative splicing isoforms Ik1 and Ik2 were significantly associated with rs4917014 genotypes. CONCLUSION: We identified IKZF1 as a susceptibility gene for CM-SJS/TEN with SMI not only in Japanese subjects but also in Korean and Indian subjects and showed that the Ik2/Ik1 ratio might be influenced by IKZF1 single nucleotide polymorphisms, which were significantly associated with susceptibility to CM-SJS/TEN with SMI.

Meibography health score: a simple grading system for isotretinoin-induced meibography alterations on patients with acne vulgaris.

PURPOSE: To develop a simple, subjective, and reliable grading scale for isotretinoin-induced meibography changes. METHODS: After analyzing meibography images obtained from systemic isotretinoin users, a grading scale was proposed and named "meibography health score." The score ranged from 1 to 3, with decreasing gland reflectivity and identifiable margins. A total of 11 medical professionals were asked to grade 10 meibography images obtained from isotretinoin users using the proposed scale and were divided into three groups: (A) ophthalmologists with experience with meibography, (B) ophthalmologists with no experience with meibography, and (C) radiologists. The kappa statistic was determined to test interrater reliability. RESULTS: The overall kappa was approximately 0.64. The kappa scores for Groups A, B, and C were 0.78, 0.59, and 0.90, respectively. Grade 2 had the lowest kappa scores (0.62, 0.35, and 0.82 for A, B, and C, respectively) and grade 3 the highest (0.78, 0.90, and 1.0 for A, B and C, respectively). Furthermore, Group C had the highest kappa scores and Group B the lowest. CONCLUSION: The meibography health score exhibited good interrater reliability, particularly in severe cases.

Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation.

Purpose: To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high-risk corneal transplantation. Design: Secondary analysis of prospective, randomized, double-blind, placebo-controlled multicentric clinical trial. Participants: The study includes patients aged > 18 years who underwent high-risk penetrating keratoplasty, which was defined as corneal vascularization in ≥ 1 quadrants of the corneal graft and host bed, excluding the limbus. Methods: Patients were randomized to treatment and control groups. The patients in the treatment group received subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) on the day of the procedure, followed by topical bevacizumab (10 mg/ml) 4 times per day for 4 weeks. The patients in control group received injection of vehicle (0.9% sodium chloride) on the day of procedure, followed by topical vehicle (carboxymethylcellulose sodium 1%) 4 times a day for 4 weeks. Main Outcome Measures: Vessel and invasion area of vessels in the corneal graft and host beds. Results: This study included 56 eyes of 56 patients who underwent high-risk corneal transplantation, with equal numbers in the bevacizumab and vehicle (control) treatment groups. The mean age of patients who received bevacizumab was 61.2 ± 15.9 years, and the mean age of those treated with vehicle was 60.0 ± 16.1 years. The vessel area at baseline was comparable in the bevacizumab (16.72% ± 3.19%) and control groups (15.48% ± 3.12%; P = 0.72). Similarly, the invasion areas were also similar in the treatment (35.60% ± 2.47%) and control (34.23% ± 2.64%; P = 0.9) groups at baseline. The reduction in vessel area was significantly higher in the bevacizumab-treated group (83.7%) over a period of 52 weeks compared with the control group (61.5%; P < 0.0001). In the bevacizumab-treated group, invasion area was reduced by 75.8% as compared with 46.5% in the control group. The vessel area was similar at 52 weeks postprocedure in cases of first (3.54% ± 1.21%) and repeat (3.80% ± 0.40%) corneal transplantation in patients who received bevacizumab treatment. In the vehicle-treated patients, the vessel area was significantly higher in repeat (9.76% ± 0.32%) compared with first (8.06% ± 1.02%; P < 0.0001) penetrating keratoplasty. In the bevacizumab treatment group, invasion areas at week 52 were comparable in first (11.70% ± 3.38%) and repeat (11.64% ± 1.74%) procedures, whereas invasion area was significantly higher in repeat (27.87% ± 2.57%) as compared with first (24.11% ± 2.17%) penetrating keratoplasty in vehicle-treated patients. Conclusions: In patients undergoing vascularized high-risk corneal transplantation, bevacizumab is efficacious in reducing vascularization of corneal graft and host bed, thereby reducing the risk of corneal graft rejection in vascularized host beds. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Age-related dysfunction of the lacrimal gland and oxidative stress: evidence from the Cu,Zn-superoxide dismutase-1 (Sod1) knockout mice.

An imbalance between free radical generation and radical scavenging antioxidant systems results in oxidative stress, which has been associated with cell injury observed in many age-related diseases. The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase-1 (Sod1) in mice leads to many different phenotypes that resemble accelerated aging. In this study we examined the morphologic features and the secretory functions of the lacrimal glands in Sod1(-/-) mice. Lacrimal glands showed atrophy of acinar units; fibrosis; infiltration with CD4(+) T cells, monocytes, and neutrophils; increased staining with both 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine; increases in apoptotic cells; and the presence of the epithelial-mesenchymal transition in senescent Sod1(-/-) mice. Electron microscopy findings revealed evidence of epithelial-mesenchymal transition, presence of swollen and degenerated mitochondria, and the presence of apoptotic cell death in the lacrimal glands of senescent Sod1(-/-) mice. These alterations were also associated with the accumulation of secretory vesicles in acinar epithelial cells, decreased production of both stimulated and nonstimulated tears, and a decline in total protein secretion from the lacrimal glands. Our results suggest that Sod1(-/-) mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated lacrimal gland alterations.

Long-term Safety and Efficacy of Corneal Collagen Crosslinking in a Pediatric Group With Progressive Keratoconus: A 7-year Follow-up.

PURPOSE: To assess effectiveness and safety of corneal crosslinking (CXL) to reduce keratoconus (KC) progression and improve visual acuity among children with progressive KC and to analyze the use of 20% dextran-based (Dextran) and 1% hydroxypropyl methylcellulose-based (HPMC) riboflavin. DESIGN: Prospective, clinical cohort study METHODS: Standard CXL (SCXL) was performed in 74 eyes (58 patients, 45 males, mean age 13.0 ± 2.1 years): 53 eyes with HPMC and 21 with Dextran. Examinations were performed at baseline, 3 and 6 months, and 1, 2, 3, 4, 5, and 7 years of follow-up, including uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), a complete ophthalmologic examination, anterior segment ocular coherence tomography, Scheimpflug corneal tomography, and specular microscopy. RESULTS: UDVA and CDVA improved at all periods with statistically significant differences in CDVA at 1, 2, and 3 years. Compared with baseline, maximum K (Max K) reduced throughout the 7-year follow-up. Mean thinnest pachymetry (Th Pachy) decreased significantly at 3 months and remained low; in the Dextran group, the Th Pachy mean value returned to baseline 6 months postoperatively. After CXL, 1.5 diopter progression in max K was 1.4% to 14.6% of eyes; worsening was found at 4 to 7 years postoperatively. CONCLUSION: SCXL reduced KC progression in children up to 7 years of follow-up and revealed improvement and stability of UDVA and CDVA in 82% of eyes. For visual acuity and KC stability, no statistically significant difference was observed between Dextran-HPMC. The HPMC group showed persistent cornea thinning, raising concerns about its use in SCXL.

TFOS Lifestyle Report: Impact of environmental conditions on the ocular surface.

Environmental risk factors that have an impact on the ocular surface were reviewed and associations with age and sex, race/ethnicity, geographical area, seasonality, prevalence and possible interactions between risk factors are reviewed. Environmental factors can be (a) climate-related: temperature, humidity, wind speed, altitude, dew point, ultraviolet light, and allergen or (b) outdoor and indoor pollution: gases, particulate matter, and other sources of airborne pollutants. Temperature affects ocular surface homeostasis directly and indirectly, precipitating ocular surface diseases and/or symptoms, including trachoma. Humidity is negatively associated with dry eye disease. There is little data on wind speed and dewpoint. High altitude and ultraviolet light exposure are associated with pterygium, ocular surface degenerations and neoplastic disease. Pollution is associated with dry eye disease and conjunctivitis. Primary Sjögren syndrome is associated with exposure to chemical solvents. Living within a potential zone of active volcanic eruption is associated with eye irritation. Indoor pollution, "sick" building or house can also be associated with eye irritation. Most ocular surface conditions are multifactorial, and several environmental factors may contribute to specific diseases. A systematic review was conducted to answer the following research question: "What are the associations between outdoor environment pollution and signs or symptoms of dry eye disease in humans?" Dry eye disease is associated with air pollution (from NO2) and soil pollution (from chromium), but not from air pollution from CO or PM10. Future research should adequately account for confounders, follow up over time, and report results separately for ocular surface findings, including signs and symptoms.

Severe ocular complications of SJS/TEN and associations among pre-onset, acute, and chronic factors: a report from the international ophthalmology collaborative group.

We formed an international research collaboration that included Japan, South Korea, Brazil, Thailand, Taiwan, the UK, and the US (682 patients from 13 hospitals between 2005 and 2020), to better evaluate the role of race, ethnicity, and other risk factors in the pathophysiology of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Ophthalmologists often see SJS/TEN patients with severe ocular complications (SOC; frequency 50% SJS/TEN patients) when the patients are referred to them in the chronic stage after the acute stage has passed. Global data were collected using a Clinical Report Form, capturing pre-onset factors, as well as acute and chronic ocular findings. Key conclusions of this retrospective observational cohort study were as follows: (1) Ingestion of cold medications [acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs)] was significantly and positively correlated with trichiasis, symblepharon, and/or conjunctivalization of the cornea in the chronic stage; (2) common cold symptoms prior to onset of SJS/TEN were significantly and positively correlated with acute conjunctivitis and ocular surface erosions in the acute stage and with trichiasis and symblepharon and/or conjunctivalization of the cornea in the chronic stage; (3) patients with SJS/TEN who presented with SOC tended to be female; (4) patients less than 30 years of age are more likely to develop SOC in the acute and chronic stages of SJS/TEN; (5) patients with acute severe conjunctivitis with ocular surface erosion and pseudomembrane formation in the acute stage are more likely to develop ocular sequelae in the chronic stage; and (6) onychopathy in the acute stage was positively correlated with ocular sequelae in the chronic stage. Our findings show that the ingestion of cold medications, common cold symptoms prior to the onset of SJS/TEN, and a young age might strongly contribute to developing the SOC of SJS/TEN.

In vivo confocal microscopy evaluation of meibomian gland dysfunction in atopic-keratoconjunctivitis patients.

PURPOSE: To clarify meibomian gland (MG) alterations in atopic keratoconjunctivitis (AKC) patients and compare the findings with obstructive MG dysfunction (MGD) patients and control subjects using in vivo confocal microscopy (CM). DESIGN: Prospective, controlled, single-center study. PARTICIPANTS: Twelve AKC patients (10 males, 2 females; mean age, 31.0±16.5 years), 12 obstructive MGD patients (7 males, 5 females; mean age, 37.6±5.6 years), and 26 control subjects (13 males, 13 females; mean age, 32.9±5.7 years) were recruited. No significant age or gender differences were observed between the 3 groups. METHODS: All subjects underwent assessment of tear evaporation rate from the ocular surface (TEROS), slit-lamp examinations, tear break-up time (BUT) measurements, vital staining, Schirmer test I, meibography, MG expressibility, and CM examination of the MG (HRTII-RCM). Statistical analysis was performed using the Mann-Whitney test. MAIN OUTCOME MEASURES: The MG acinar unit density, inflammatory cell density, MG acinar unit longest diameter, MG acinar unit shortest diameter, and MG acinar unit area as observed by in vivo CM, MG drop-out, MG expressibility grading, tear stability, tear evaporation, and vital staining scores. RESULTS: The TEROS values, mean BUT, vital staining scores, MG expressibility, and MG dropout grades were significantly worse in AKC patients compared with those in obstructive MGD patients and controls (P<0.05). The mean values of the CM parameters in AKC patients were significantly worse than those observed in the obstructive MGD patients and controls (P<0.001). CONCLUSIONS: Changes in MG in AKC patients seem to be more severe than in patients with obstructive MGD and controls. In vivo CM is a noninvasive, efficient tool in the assessment of MG status and ocular surface disease in AKC.

OCT assessment of tear meniscus after punctal occlusion in dry eye disease.

PURPOSE: To evaluate the tear meniscus changes after punctal occlusion in dry eye patients using Visante optical coherence tomography (OCT) in a prospective controlled study. METHODS: Thirty eyes of 15 symptomatic dry eye patients not responding to non-preserved artificial tears received additional upper and lower punctal occlusion with silicone plugs, and 30 eyes of 15 age- and sex-matched dry eye control patients received only non-preserved artificial tears treatment for 1 month. All subjects underwent tear meniscus height (TMH) measurements with Visante OCT. All study participants also underwent slitmicroscopy graticule scale TMH measurement, strip meniscometry testing, tear film break-up time measurement, ocular surface vital staining with fluorescein and Rose Bengal dyes, and the Schirmer-1 test. Both groups, dry eye and control group patients, were examined before and after 1-month treatment. Wilcoxon-matched pair test was performed. The study was conducted in compliance with the Tenets of the Declaration of Helsinki. RESULTS: TMH measurements by OCT and slitlamp graticule scale significantly improved after punctal occlusion (p < 0.001) and remain unchanged in the dry eye control patients. Similarly, strip meniscometry scores, mean tear stability values, Rose Bengal, and fluorescein staining scores showed significant improvement after punctal occlusion (p < 0.05). Schirmer-1 test values tended to be higher after 1 month of treatment in both groups without any statistical significance (p > 0.05). CONCLUSIONS: OCT TMH measurement appears to be effective in monitoring tear meniscus changes after punctal occlusion. OCT can be a valuable non-invasive and quick clinical tool for evaluation of treatment responses in dry eye patients.

Correlation between Placido-disc and rotating Scheimpflug keratometric findings before and after corneal crosslinking in children with keratoconus.

PURPOSE: To evaluate correlation between Placido-disc and rotating Scheimpflug keratometric findings in children with progressive keratoconus (KC) before and after corneal crosslinking (CXL) and investigate whether these limits of agreement varied according to disease severity. SETTING: Department of Ophthalmology of São Paulo Hospital, São Paulo, Brazil. DESIGN: Prospective nonrandomized open study. METHODS: Data obtained using rotating Scheimpflug-based tomography and Placido-disc-based topography devices were collected from preoperative and last follow-up postoperative children with KC operated on using standard CXL protocol. Correlation and agreement analyses were performed between the 2 devices before and after CXL to obtain keratometric (K) findings. RESULTS: 44 eyes from 44 patients aged 8 to 16 years were analyzed at all timepoints. All parameters were found to be strongly correlated before ( r = 0.84 to 0.99, P < .001) and after ( r = 0.93 to 0.99, P < .001) CXL. The mean Scheimpflug measurements of flat K, steep K, Kmax, mean K, and corneal astigmatism were higher than Placido-disc measurements in a preoperative period. This mean difference decreased in postoperative, but, with exception of Kmax and corneal astigmatism, Scheimpflug measurements remained higher. The mean parameter measurements from both devices decreased after CXL; 95% limits of agreement between instruments were wide for all parameters and decreased in postoperative and in mild KC. CONCLUSIONS: Keratometry measurements obtained using rotating Scheimpflug and Placido-disc technology were found to be closely correlated but not interchangeable before and after CXL in pediatric patients. Agreement between devices was better after CXL and in mild KC than in advanced KC.

Prevalence and risk factors for dry eye disease: the Sao Paulo dry eye study.

PURPOSE: To estimate the prevalence and risk factors of dry eye disease symptoms and clinical diagnoses in Sao Paulo city, state of Sao Paulo, Brazil. METHODS: A total of 582 participants over 18 years old, living in the east zone of Sao Paulo city responded to a short questionnaire. Dry eye disease was on that is defined by the presence of severe symptoms or previous clinical diagnosis of dry eye disease by an ophthalmologist. The association between dry eye disease and possible risk factors was assessed. RESULTS: Overall dry eye disease severe symptoms and/or clinical diagnoses prevalence was calculated as 24.4% for both sexes. Women presented a higher frequency of severe symptoms of dry eye disease (16.07%) than men (8.48%; p=0.0244), as well as the composite of severe symptoms or diagnosed dry eye disease, presented by 26.86% of women and 18.18% of men (p=0.0366). In women, ages between 55 to 75 years old were associated with dry eye disease severe symptoms (OR=3.11; 95%CI 1.56-6.23, p=0.001) and diagnosed dry eye disease (OR=2.02; 95% CI 1.04-3.93, p=0.037). Hypertension was significantly associated with dry eye disease symptoms (OR=1.98; 95% CI 1.14-3.43, p=0.015) and diagnoses (OR=3.54; 95% CI 1.92-6.53, p=0.0001) in women. Eye drops use was associated with severe symptoms of dry eye disease and diagnosed dry eye disease in both women and men (p≤0.01). CONCLUSIONS: Dry eye disease prevalence in Sao Paulo city is higher in women than in men. Age and hypertension were stronger risk factors of dry eye disease for women, while eye drops use was a significant indicator of dry eye disease for both sexes.

Eosinophil cationic protein as a marker for assessing the efficacy of tacrolimus ophthalmic solution in the treatment of atopic keratoconjunctivitis.

PURPOSE: To examine the clinical efficacy and anti-inflammatory effects of tacrolimus eye drops; we studied the changes in clinical ocular findings and measured tear eosinophil cationic protein (ECP) levels of atopic keratoconjunctivitis (AKC) patients before and after the treatment. METHODS: Nine eyes of 9 patients (8 males, 1 female; mean age: 16.9 ± 11.4 years; range: 6-44 years) diagnosed with moderate or severe AKC disease were enrolled in this prospective study and treated with tacrolimus. All patients received 0.1% tacrolimus eye drops 2 times a day for 1 month. Tear samples were taken before and after treatment and ECP concentrations were obtained. Corneal fluorescein staining and conjunctival injection, edema, and papillary formation were graded on the recruitment day and one month later. Analysis of pre- and post-treatment findings was done using the Wilcoxon signed test. The ECP concentrations were correlated with the clinical signs using Spearman correlation tests. RESULTS: Post-treatment tear ECP levels were significantly reduced compared to the pre-treatment level. Clinical corneal scores also improved significantly after one month treatment with tacrolimus eye-drops. The mean conjunctival injection and conjunctival edema scores were significantly (p<0.05) decreased after the drug therapy. Strong positive linear correlations between ECP values and clinical signs were observed. Patients did not present side effects during the treatment with tacrolimus. CONCLUSIONS: In this pilot study, tacrolimus eye drops were found to reduce signs of AKC. ECP proved to correlate well with clinical signs of AKC.

Prevalence and associated risk factors for dry eye disease among Brazilian undergraduate students.

PURPOSE: Dry eye is a common, complex, and multifactorial disease of the ocular surface and tear film that results in discomfort and visual disturbances. Prevalence rates vary and largely rely on studies involving older populations. This study sought to evaluate dry eye among a sample of young students in Brazil. METHODS: Cross-sectional survey included 2,140 students using 2 self-applicable questionnaires of dry eye symptoms: the Ocular Surface Disease Index (OSDI) and the Women's Health Study (WHS) questionnaire and a list of risk factors associated with dry eye. Participants with dry eye symptoms underwent a clinical evaluation. RESULTS: Participants were 23.4±5.2 years of age, 56.1% female and 43.9% male, 34.4% had an OSDI score greater than 22, and 23.5% had dry eye according to the WHS. Dry eye frequency differed consistently between the sexes: 42.6% women and 24.0% men based on the OSDI, and 27.1% women and 18.5% men based on the WHS. Univariate and multivariate analyses demonstrated that female sex, contact lens wear, the screen use for more than 6 hours per day, less than 6 hours of sleep a night, and certain medications were relevant related risk factors for dry eye. Despite symptoms, clinical evaluations demonstrated mild signs of dry eye. CONCLUSIONS: Dry eye symptoms were found to be a prevalent condition among Brazilian undergraduate students. Compared to the rates of dry eye among the general Brazilian population over 40 years of age, students present at higher dry eye symptoms rates and distinct odds for related risk factors were identified.

Clinical Aspects of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis With Severe Ocular Complications in Brazil.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute and potentially fatal inflammatory vesiculobullous reactions that affect the skin and mucous membranes, and which are most often triggered by particular medications and infections. In Brazil, the drugs most frequently associated with TEN and SJS include cold medicine such as dipyrone and NSAIDs, followed by carbamazepine, phenobarbital, penicillin, and allopurinol. Genetic variations have been found to increase the risk of SJS/TEN in response to triggering factors such as medications. The most closely associated genes found in Brazilian cold-medicine-related SJS/TEN patients with severe ocular complications are HLA-A*66:01 in those of mixed African and European ancestry and HLA-B*44:03 and HLA-C*12:03 in those of solely European ancestry. Our classification system for grading ocular surface complication severity in SJS/TEN patients revealed the most severe complications to be limbal stem cell deficiency and dry eye. Changes to the conjunctival flora have also been observed in SJS/TEN patients. Our group identified bacterial colonization in 95% of the eyes (55.5% of which were gram-positive cocci, 25.5% of which were gram-negative bacilli, and 19% of which were gram-positive bacilli). Several new treatment options in the acute and chronic ocular management of the SJS/TEN patients have been described. This article highlights some Brazilian institutions' contributions to ocular surface care in both the acute phase (including the use of amniotic membrane transplantation) and the chronic phase (such as eyelid margin and fornix reconstruction, minor salivary gland transplantation, amniotic membrane and limbal transplantation, scleral contact lenses, anti-angiogenic eyedrops for corneal neovascularization, ex-vivo cultivated limbal epithelium transplantation, conjunctival-limbal autografting, oral mucosa transplantation, and keratoprosthesis).

Evaluation of lipid oxidative stress status and inflammation in atopic ocular surface disease.

BACKGROUND: Although the oxidative stress status in atopic skin disease has been reported to be elevated, there are still no studies related to the status of oxidative stress in atopic ocular surface disease. The purpose of this study was to evaluate the ocular surface lipid oxidative stress status and inflammation in atopic keratoconjunctivitis (AKC) patients and normal subjects. METHODS: Twenty eight eyes of 14 patients (9 males, 5 females) with AKC and 18 eyes of 9 age and sex matched (4 males and 5 females) normal healthy controls were examined in this prospective study. The severity of atopic dermatitis (AD) was scored by the SCORing Atopic Dermatitis (SCORAD) index. All subjects underwent Schirmer test, tear film break up time (BUT), fluorescein/Rose Bengal stainings, tear collection, and brush cytology from the upper palpebral conjunctiva. The brush cytology samples were stained with Diff-Quik for differentiation of inflammatory cells and immunohistochemistry (IHC) staining with HEL (hexanoyl-lysine) and 4-HNE (4-hydroxy-2-nonenal) to study lipid oxidation. HEL and cytokine (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ)) levels were measured by enzyme-linked immunosorbent assay (ELISA) from tear samples of AKC patients and control subjects. Toluidine Blue and IHC staining with HEL, 4-HNE and cluster of differentiation 45 (CD45) were performed on papillary samples of AKC patients. This study was conducted in compliance with the "Declaration of Helsinki." RESULTS: The tear stability and vital staining scores were significantly worse in eyes of AKC patients (p<0.05) compared to the controls. Inflammatory cells and positively stained conjunctival epithelial cells for HEL and 4-HNE showed a significant elevation in brush cytology samples of AKC patients. Significantly higher levels of HEL and cytokines were detected in tears of AKC patients compared to controls. Papillary specimens also revealed many CD45 inflammatory cells as well as many cells positively stained with HEL and 4-HNE in IHC. A strong significant linear positive correlation between conjunctival inflammation and epithelial lipid oxidative stress status was observed. Conjunctival lipid oxidative stress also correlated strongly with tear HEL levels and epithelial damage scores. CONCLUSIONS: The ocular surface disease in AKC was characterized by marked tear instability, ocular surface epithelial damage, increase in inflammatory infiltrates and presence of increased lipid oxidation.

The efficacy, sensitivity, and specificity of in vivo laser confocal microscopy in the diagnosis of meibomian gland dysfunction.

PURPOSE: To evaluate the efficacy, sensitivity and specificity of confocal microscopy (CM) parameters: meibomian gland (MG) acinar longest diameter (MGALD), MG acinar shortest diameter (MGASD), inflammatory cell density (ICD), and MG acinar unit density (MGAUD) in the diagnosis of MG dysfunction (MGD). DESIGN: Prospective, controlled, single-center study. PARTICIPANTS: Twenty MGD patients (9 males, 11 females; mean age, 63.5+/-16.5 years) and 26 age- and gender-matched control subjects (13 males, 13 females; mean age, 53.2+/-15.7 years) were recruited. METHODS: All subjects underwent slit-lamp examinations, tear film break-up time (BUT) measurements, assessment of tear evaporation rate from the ocular surface (TEROS), vital stainings, Schirmer test, meibography, MG expressibility, and CM of the MG. Data were compared between the 2 groups using the Mann-Whitney and chi-square tests. MAIN OUTCOME MEASURES: The correlation between the clinical findings of tear functions, vital staining scores, and the 4 CM parameters were tested by Spearman's correlation coefficient by rank test. Receiver operating characteristic curve technique was used to evaluate the sensitivity, specificity, and cutoff values of CM parameters. RESULTS: The mean tear film BUT, vital staining scores, TEROS values, MG expressibility, and MG dropout grades by meibography were significantly worse in MGD patients compared with controls (P<0.001). The mean values of the MGALD, MGASD, ICD, and MGAUD in MGD patients were significantly worse than those observed in the controls with CM. All CM parameters showed a strong, significant correlation with tear functions, ocular surface vital stainings, MG expressibility, and MG dropout grades. The cutoff values for MGALD, MGASD, ICD, and MGAUD in the diagnosis of MGD were 65 microm, 25 microm, 300 cells/mm2, and 70 glands/mm2, respectively. The sensitivity and specificity values of these parameters under these cutoff values were 90% and 81% for MGALD, 86% and 96% for MGASD, 100% and 100% for ICD, 81% and 81% for MGAUD. CONCLUSIONS: Confocal microscopy has the potential to diagnose the simple MGD with high sensitivity and specificity. The CM-based diagnostic parameters correlated significantly and strongly with the status of the ocular surface disease. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Application of visante optical coherence tomography tear meniscus height measurement in the diagnosis of dry eye disease.

PURPOSE: To investigate the applicability of tear meniscus height (TMH) measurement using Visante optical coherence tomography (OCT) in the diagnosis of dry eye disease. DESIGN: Prospective, controlled, single-center study. PARTICIPANTS: Twenty-four right eyes of 24 patients (6 males, 18 females; mean age, 63.14±13.4 years) with definite dry eye according to the Japanese dry eye diagnostic criteria and 27 right eyes of 27 control subjects (12 males, 15 females; mean age, 56.04±14.22 years) were recruited. METHODS: All subjects underwent slit-lamp TMH measurement, OCT upper and lower TMH measurements, tear film breakup time (BUT) measurements, vital stainings, and Schirmer test. The results were compared between the 2 groups by Mann-Whitney test. MAIN OUTCOME MEASURES: The correlation between the clinical findings of slit-lamp TMH, strip meniscometry examination, tear functions, vital staining scores, and the OCT upper and lower TMH parameters were tested by Spearman's correlation test. Receiver operating characteristic (ROC) curve technique was used to evaluate the sensitivity, specificity and cutoff values of OCT TMH examination in the diagnosis of dry eye. RESULTS: The OCT upper and lower TMH values, slit-lamp TMH, strip meniscometry, tear film BUT, and vital staining scores were significantly lower in the dry eye patients compared with controls (P<0.001). A significant correlation between the OCT upper and lower TMH measurements as well as slit-lamp TMH, strip meniscometry, tear functions, vital staining scores, and the Schirmer test was found. The ROC curve technique analysis of the OCT lower TMH showed that, when the cutoff value was set at <0.30 mm, the sensitivity and specificity of the testing were 67% and 81%, respectively. CONCLUSIONS: The Visante OCT is a quick, noninvasive method for assessing the TMH, with acceptable sensitivity, specificity, and repeatability, and may have potential applications for the diagnosis and evaluation of dry eye disease.

Passive cigarette smoke exposure and soft contact lens wear.

PURPOSE: To prospectively investigate the effects of passive cigarette smoke exposure on the ocular surface and tear film in soft contact lens (SCL) wearers. METHODS: Twelve right eyes of 12 SCL wearers without any ocular or systemic diseases and 10 right eyes of 10 subjects who never wore CLs were examined before and 2 h after 5 min of passive cigarette smoke exposure in a controlled smoke chamber. Tear evaporation rate measurement, tear film break-up time (TBUT) examination, ocular surface fluorescein, rose bengal stainings, and Schirmer I test were performed at each visit. RESULTS: The mean tear evaporation rates, TBUTs, and vital staining scores were significantly worse in CL wearers compared with healthy control subjects. TBUTs showed significant worsening after passive smoke exposure in both groups. The mean tear evaporation rate and vital staining scores showed a significant increase with brief passive smoke exposure in subjects not wearing CLs but not in CL wearers. CONCLUSION: Even brief passive exposure to cigarette smoke is associated with adverse effects on the ocular surface as evidenced by an increase in tear instability and damage to the ocular surface epithelia in SCL wearers and non-CL wearers.