Inflammation-related molecules in tears of patients with chronic ocular pain and dry eye disease.

The purpose of this study was to analyze inflammation- and pain-related molecules in tears of patients suffering from chronic ocular pain associated with dry eye (DE) and/or a previous corneal refractive surgery (RS). Based on history, symptomatology, and clinical signs, the subjects (n = 180, 51.0 ± 14.7 years, 118 females, 62 males) in this cross-sectional study were assigned to one of five groups: DE and chronic ocular pain after RS (P/DE-RS, n = 52); asymptomatic subjects, i.e., without DE and chronic ocular pain, after RS (A-RS, n = 30); DE and chronic ocular pain without previous RS (P/DE-nonRS, n = 31); DE, no pain, and no previous RS (DE-nonRS, n = 35); and asymptomatic subjects with no previous RS (controls, n = 32). The tear concentrations of 20 cytokines and substance P (SP) were analyzed by immunobead-based assay and enzyme-linked immunosorbent assay, respectively. We found that tear levels of interleukin (IL)-10 and SP were increased in the RS groups. There were significant differences in IL-8/CXCL8 among the five groups. Nerve growth factor (NGF) tear levels were significantly higher in P/DE-RS than in DE-nonRS and controls. IL-9 had the highest percentage of detection in the P/DE-RS and P/DE-nonRS groups, while macrophage inflammatory protein (MIP)-1α, IL-2, and interferon (IFN)-γ were higher in the P/DE-RS, A-RS, and P/DE-nonRS groups. IL-17A was detected only in the A-RS group. Moderate correlations were observed in the A-RS, P/DE-nonRS, DE-nonRS and controls groups. A positive correlation was obtained between growth related oncogene concentration and tear break-up time (rho = 0.550; p = 0.012), while negative correlation was found between monocyte chemoattractant protein-3/CCL7 and conjunctival staining (rho = -0.560; p = 0.001), both in the A-RS group. IL-10 correlated positively with ocular pain intensity (rho = 0.513; p = 0.003) in the P/DE-nonRS group. Regulated on Activation Normal T Cell Expressed and Secreted/CCL5 correlated negatively with conjunctival staining (rho = -0.545; p = 0.001) in the DE-nonRS group. SP correlated negatively with corneal staining (rho = -0.559; p = 0.001) in the controls. In conclusion, chronic ocular pain was associated with higher IL-9 tear levels. IL-10, SP, MIP-1α/CCL3, IL-2, and IFN-γ were associated with previous RS. Higher levels of IL-8/CXCL8, MIP-1α/CCL3, IL-2, and IFN-γ were associated with DE-related inflammation, while NGF levels were related to chronic ocular pain and DE in RS patients. These findings suggest that improved knowledge of tear cytokines and neuromodulators will lead to a more nuanced understanding of how these molecules can serve as biomarkers of chronic ocular pain, leading to better therapeutic and disease management decisions.

Progression of myopic maculopathy in a Caucasian cohort of highly myopic patients with long follow-up: a multistate analysis.

PURPOSE: This study aims to determine the probability of progression of myopic maculopathy according to age. METHODS: This is a longitudinal observational study of single-center retrospective cohort of Caucasian patients formed by 212 consecutive adults with high myopia. Main outcome measures were age, visual acuity (VA), refractive error (RE), follow-up time, and the macular status assessed at least 5 years apart according to the Meta-Analysis of Pathologic Myopia Study Group. The progression rate was calculated based on per 1000 eyes/year. Multistate models were fitted to identify the predictive factors and to calculate the most probable age of progression onset using the Aalen-Johansen estimator. RESULTS: We studied 220 eyes of 122 Caucasian patients. Mean age was 48.18 ± 14.1, mean follow-up 12.73 ± 5.81 years. One-hundred and fifty-two (69.1%) eyes progressed of category, and 96 (44%) worsened a mean of 0.3 logMAR units during follow-up. The progression rate was 32.21/1000 eyes/year. The probability of progressing increased with age; it was higher in women if there was a family history of myopia, worse VA, higher RE, or wide macular staphyloma. The probability of progressing from category 1 was > 0.6 after 70 years of age; from category 2, it was 0.7 after 70 years; and 0.5 from category 3 after 75 years. If choroidal neovascularization (CNV) appeared, this probability exceeded 0.7 between ages 45 and 55 for all categories. CONCLUSION: The progression rate is lower than in a Japanese series. The vision worsened with disease progression, and the probability of both happening increased after the age of 70-75. If CNV appears, the risk of progression is very high at the age of 45-55.

Monochromatic higher order aberrations in highly myopic eyes with Staphyloma.

BACKGROUND: Prevalence of high myopia is continuously increasing, thus, patients affected with staphyloma are abundant worldwide. Assessment of the quality of vision in these patients is mandatory for a proper clinical counselling, specially when undergoing surgical procedures that require intraocular lenses implantation. Thus, the purpose of the study was to assess monochromatic higher order aberrations (HOAs) in highly myopic eyes with staphyloma with or without a dome-shaped macula. METHODS: Participants underwent spectral-domain optical coherence tomography, ocular axial biometry, dual Scheimpflug photography and integrated Placido disk topography, and Hartmann-Shack wavefront analysis. Five groups were evaluated: a low-moderate myopia control group (< 6.00 diopters, n = 31) and four high myopia (≥6.00 diopters) groups: eyes without staphyloma (n = 18), eyes with inferior staphyloma (n = 14), eyes with posterior staphyloma without dome-shaped macula (n = 15) and eyes with posterior staphyloma with dome-shaped macula (n = 17). Subsequently, two new groups (including all participants) were created to assess differences between myopia with and without staphyloma. One-way analysis of covariance was performed using age and lens densitometry as covariates. RESULTS: Statistically significant (p ≤ 0.05) differences in anterior corneal fourth-order HOAs were observed between the low-moderate myopia and no-dome-shaped macula (Mean: 0.16 µm) and dome-shaped macula posterior staphyloma groups (Mean: 0.12 µm) in younger patients (≤45 years old). The same groups also showed (p ≤ 0.05) significant differences for anterior corneal primary spherical aberration (Mean: 0.19 and 0.13 µm, respectively). In addition, anterior corneal tetrafoil was significantly higher (p = 0.04) in dome-shaped macula compared to no-dome-shaped macula (Mean: 0.18 vs 0.06 µm, respectively). When all participants were grouped together, significantly lower mean anterior corneal primary spherical aberration (0.15 µm vs. 0.27 µm, p = 0.004) and higher internal primary spherical aberration (0.04 µm vs. -0.06 µm, p = 0.04) was observed in staphyloma compared to no-staphyloma myopic patients. CONCLUSIONS: Eyes with high myopia and staphyloma have less positive anterior corneal primary spherical aberration and less negative internal primary spherical aberration, suggesting that the anterior corneal surface tends to mimic in a specular fashion the posterior pole profile. This corneal behaviour appears to change in patients older than 45 years.

Development of a Questionnaire for Detecting Changes in Dry Eye Disease-Related Symptoms.

OBJECTIVES: Determining the changes in symptomatology suffered by dry eye disease (DED) patients after an intervention is difficult because there is only one validated questionnaire specifically designed to measure these changes and it is somewhat complex. This work uses a simplified questionnaire to evaluate the changes in DED-related symptoms. METHODS: A new questionnaire based on a global rating of change scale was designed. The Change in Dry Eye Symptoms Questionnaire (CDES-Q) consists of 2 questions: CDES-Q1 asks for the change in symptoms ("better," "same," or "worse") relative to a determined previous time and CDES-Q2 quantifies this change (range: 0 to +100). To evaluate the CDES-Q, a prospective observational study was performed. At baseline (V1; day-0), DED-related symptoms were evaluated using the ocular surface disease index (OSDI). In the post-treatment visit (V2; day-90), OSDI, Symptoms Assessment Questionnaire in Dry Eye (SANDE) II, and CDES-Q were used. Also, clinical evaluations were performed in each visit. RESULTS: Thirty-six patients were included. At V2, OSDI, SANDE II, and CDES-Q showed a significant reduction in symptoms (-7.17±12.73, P=0.0021; -11.29±20.95, P=0.0035; -25.28±42.28, P=0.0011, respectively). Patients who answered "better" in CDES-Q1 showed a significantly lower SANDE II than those who answered "same" or "worse," while SANDE II did not discriminate between these groups. CONCLUSIONS: CDES-Q can be a useful tool for the evaluation of changes in DED-related symptoms. It is simple and better discriminates patients without changes from those who suffered a worsening than SANDE II.

Contact Lens Discomfort Management: Outcomes of Common Interventions.

PURPOSE: To assess the consecutive implementation of habitual contact lens discomfort (CLD) management strategies: lid hygiene, daily disposable CL (DDCL) fitting, and artificial tear (AT) supplementation. METHODS: Contact lens (CL) wearers with CLD symptoms (CLDEQ-8 ≥12 points) were included in the study. Subjects with Meibomian gland dysfunction (MGD) were instructed to perform lid hygiene. All participants were fitted with a DDCL (delefilcon A) and evaluated 1 month later. After, half of them were randomly assigned to use AT (Povidone-2%) at least three times/day, and all participants were evaluated 1 month later. Tests performed were: lower tear meniscus area (LTMA), bulbar, limbal, and tarsal hyperemia, noninvasive tear break-up time (NITBUT), and corneal and conjunctival staining. Weighted combined clinical scores (CS) were created to analyze signs. Changes in symptoms (CLDEQ-8) and CS were analyzed using linear mixed models. RESULTS: Forty-two subjects (mean age: 23.2±4.9 years) completed the study. Two CS were created, CS 1 was composed of bulbar, limbal, and tarsal hyperemia and corneal staining, and CS 2 by NITBUT, LTMA, and conjunctival staining. CLDEQ-8 was reduced after lid hygiene (mean: -2.73±2.13; P=0.012) and DDCL use (mean: -10.1±3.54; P<0.01), but not after AT use (P=0.62). CS 1 did not change after any intervention. CS-2 was higher (P=0.04) in DGM subjects after lid hygiene, it decreased (P=0.04) after DDCL use. CONCLUSIONS: Lid hygiene is effective for reducing CLD symptoms in MGD patients. Refitting subjects with delefilcon A is an effective intervention for CLD to reduce symptoms and achieve a healthier ocular surface. Simultaneous administration of AT did not further improve CLD.

Clinical and tear cytokine profiles after advanced surface ablation refractive surgery: A six-month follow-up.

Neuropathic dry eye is one of the most frequently seen complications after corneal refractive surgery, however, its incidence decreases in a significant manner along the first six months postoperative, reaching between 10 and 45% incidence. However, little is known on the inflammatory status of the ocular surface during this recovery process. We aim to analyze the clinical and tear molecule concentration changes along six months after advanced surface ablation for myopia correction, in a prospective study including 18 eyes of 18 subjects who bilaterally underwent advanced surface ablation corneal refractive surgery. Clinical variables (uncorrected distance visual acuity, symptoms, conjunctival hyperemia, tear osmolarity, tear stability, corneal fluorescein staining, conjunctival lissamine staining, Schirmer test, and corneal esthesiometry) and a panel of 23 pro and anti-inflammatory cytokines/chemokines concentration in tears preoperatively and at 1, 3 and 6 months postoperatively were evaluated. We found that uncorrected distance visual acuity improved significantly from baseline at 1-month visit, symptoms improved and tear osmolarity decreased significantly from baseline at 3-month visit and there was a decrease in mechanical corneal threshold between 1-month and 3- and 6-month visits. Regarding tear molecules, IL-4, IL-5, IL-6, IL-13, IL-17A, and IFN-γ tear levels were significantly increased at all the three visits, compared to preoperative levels at V0; IL-2 and VEGF were also significantly increased at 1-month and 6-month visits, but not at 3-month visit, whereas IL-9 IL-10 and IL-12 were only significantly increased at 6-month visit. Although we found that there is a recovery in clinical variables at 6 months postoperatively (i.e. neuropathic dry eye was not developed in the sample), ocular surface homeostasis is not completely restored, as it can be seen by the changes in concentration of some pro and anti-inflammatory molecules measured in tears.

Classification of Keratoconus Based on Anterior Corneal High-order Aberrations: A Cross-validation Study.

SIGNIFICANCE: Placido disc-based videokeratography is one of the most extensively used methods for corneal topographic assessments in keratoconus. Anterior corneal wavefront analysis has been demonstrated to be an effective tool to manage keratoconus eyes. However, currently, there is no clinically adequate classification system for keratoconus. PURPOSE: The aim of this study was to analyze the usefulness of anterior corneal high-order aberrations in keratoconus classification provided by Placido disc-based videokeratography conducting a cross-validation analysis. METHODS: Corneal topography of 70 normal and 77 keratoconic eyes (divided according to the Amsler-Krumeich classification [n = 21, stage 1; n = 30, stage 2; and n = 26, stage 3]) was assessed using Placido disc-based videokeratography (Oculus Keratograph [Oculus Optikgeräte GmbH, Wetzlar, Germany]). Receiver operating characteristic curve analysis was used to compare the mean values of coma, trefoil, tetrafoil, secondary astigmatism, spherical aberration, and coma-like, third-, and fourth-order root mean square (RMS) to calculate cutoff values, sensitivity, and specificity to discriminate between normal and stage 1 keratoconus eyes and between each keratoconus stage after cross-validation analysis. RESULTS: All wavefront aberrations were significantly different between the normal and keratoconus groups (P ≤ .01). The coma and third-order RMS values (cutoff values, 0.367 and 0.359 µm, respectively) provide better sensitivity (99 and 100%, respectively) and specificity (100%) to discriminate keratoconus (stage 1) from healthy eyes compared with trefoil, tetrafoil, secondary astigmatism, spherical aberration, and coma-like and fourth-order RMS values (sensitivity >84% and specificity >57%). The coma and third-order RMS values showed the highest specificity (100%) and great sensitivity (90 and 87%, respectively) to differentiate between stages 1 and 2 and good sensitivity (97 and 100%) and specificity (81 and 88%) to differentiate between stages 2 and 3. CONCLUSIONS: Anterior corneal high-order aberrations, specifically coma and third-order RMS, could be useful in keratoconus diagnosis and topographical classification. These new cutoff values could improve different stages of keratoconus eyes discrimination.

Visual processing speed in hemianopia patients secondary to acquired brain injury: a new assessment methodology.

BACKGROUND: There is a clinical need to identify diagnostic parameters that objectively quantify and monitor the effective visual ability of patients with homonymous visual field defects (HVFDs). Visual processing speed (VPS) is an objective measure of visual ability. It is the reaction time (RT) needed to correctly search and/or reach for a visual stimulus. VPS depends on six main brain processing systems: auditory-cognitive, attentional, working memory, visuocognitive, visuomotor, and executive. We designed a new assessment methodology capable of activating these six systems and measuring RTs to determine the VPS of patients with HVFDs. METHODS: New software was designed for assessing subject visual stimulus search and reach times (S-RT and R-RT respectively), measured in seconds. Thirty-two different everyday visual stimuli were divided in four complexity groups that were presented along 8 radial visual field positions at three different eccentricities (10o, 20o, and 30o). Thus, for each HVFD and control subject, 96 S- and R-RT measures related to VPS were registered. Three additional variables were measured to gather objective data on the validity of the test: eye-hand coordination mistakes (ehcM), eye-hand coordination accuracy (ehcA), and degrees of head movement (dHM, measured by a head-tracker system). HVFD patients and healthy controls (30 each) matched by age and gender were included. Each subject was assessed in a single visit. VPS measurements for HFVD patients and control subjects were compared for the complete test, for each stimulus complexity group, and for each eccentricity. RESULTS: VPS was significantly slower (p < 0.0001) in the HVFD group for the complete test, each stimulus complexity group, and each eccentricity. For the complete test, the VPS of the HVFD patients was 73.0% slower than controls. They also had 335.6% more ehcMs, 41.3% worse ehcA, and 189.0% more dHMs than the controls. CONCLUSIONS: Measurement of VPS by this new assessment methodology could be an effective tool for objectively quantifying the visual ability of HVFD patients. Future research should evaluate the effectiveness of this novel method for measuring the impact that any specific neurovisual rehabilitation program has for these patients.

Nidogen-2: Location and expression during corneal wound healing.

Nidogen-2 is a basement membrane (BM) glycoprotein that could be a key to understanding why defects in BM regeneration occur after severe trauma to the cornea. We monitored the location and expression of nidogen-2 during corneal repair after alkali burn in rabbits. In rabbits that received both general and ocular topical anaesthesia, the central cornea of the left eye was burned by placing an 8-mm diameter filter paper soaked in 0.5 N NaOH for 60 s. Right corneas were used as controls. The eyes were evaluated at 2, 7, 15, and 30 days after burning and analysed by immunohistochemistry for nidogen-2 and α-smooth muscle actin, a myofibroblast marker. Nidogen-2 mRNA expression levels were determined by quantitative real-time polymerase chain reaction. In control corneas, nidogen-2-positive cells were in all epithelial layers, the endothelium, and the anterior and posterior stromal regions. At Day 2 after the alkali burn, the wound area epithelium and the peripheral epithelium were made up of only 1 to 2 cell layers, all of them nidogen-2 positive. At Day 7 in the wound area, the epithelium consisted of two cell layers, and the basally located cells were mostly nidogen-2 positive. The greatest change was observed at Day 30. At this time, the ulcer prevalence in the alkali-burned corneas was approximately 50% and the central epithelial defects remained. In unepithelialized corneas, frequent epithelial detachments were present, in which almost of the epithelial cells were nidogen-2 negative. The injured stroma was repopulated by activated stromal cells that synthesized nidogen-2. The nidogen-2 was retained in the newly secreted, but disordered, matrix produced mainly by the myofibroblasts localized in the stroma at 7, 15, and 30 days after burning. Thus, even though nidogen-2 was present, it was unable to contribute to the effective regeneration of the BM.

Dynamic changes of the extracellular matrix during corneal wound healing.

The extracellular matrix (ECM) confers transparency to the cornea because of the precise organization of collagen fibrils and a wide variety of proteoglycans. We monitored the corneal wound healing process after alkali burns in rabbits. We analyzed the location and expression of collagens and proteoglycans, the clinical impact, and the recovery of optical transparency. After the animals received both general and ocular topical anesthesia, the central cornea of the left eye was burned by placing an 8-mm diameter filter paper soaked in 0.5 N NaOH for 60 s. The eyes were evaluated under a surgical microscope at 1, 3, and 6 months after burning. At each time point, the clinical conditions of the burned and control corneas were observed. The arrangement of collagen fibers in the corneal stroma was visualized by Picrosirius-red staining, Gomori's silver impregnation and transmission electronic microscopy. Corneal light transmittance was also measured. Myofibroblasts presence was analyzed by immunohistochemistry. mRNA expression levels of collagen types I and III, lumican, decorin, keratocan and alpha-smooth muscle actin were determined by quantitative real-time polymerase chain reaction. One month after alkali burn, the ECM was disorganized and filled with lacunae containing different types of cells and collagen type III fibers in the wound area. Corneal opacities were present with attendant loss of light transmittance. Collagen and proteoglycan mRNA expression levels were up-regulated. After three months, wound healing progress was indicated by reduced corneal opacity, increased light transmittance, reorganization of collagen fibers and only collagen type I expression levels were at control levels. After six months, the wound area ECM morphology was similar to controls, but transmittance values remained low, denoting incomplete restoration of the stromal architecture. This multidisciplinary study of the stromal wound healing process revealed changes in corneal transmittance, collagen organization, myofibroblasts presence and ECM composition at 1, 3, and 6 months after alkali burning. Documenting wound resolution during the six-month period provided reliable information that can be used to test new therapies.

Reliability of Blotting Techniques to Assess Contact Lens Water Content.

OBJECTIVES: To determine the reliability of wet and modified dry blotting techniques used in the gravimetric method to assess contact lens (CL) water content (WC), the accuracy of both techniques in comparison with the nominal WC, and also their agreement. METHODS: We evaluated hydrated and dry CL mass values and WC using the gravimetric method in 440 daily disposable CLs. Samples assessed corresponded to Dailies Total 1, Dailies AquaComfort Plus, 1-Day Acuvue TruEye, and Biotrue ONEday. Back vertex power ranged from +3.00 diopters (D) to -6.00 D. Within-subject coefficient of variation (CVw) and intraclass correlation coefficients were calculated. Bland-Altman analysis was also performed. RESULTS: The modified dry blotting technique yielded significantly (P≤0.0001) higher hydrated CL mass values. The wet blotting technique provided significantly (P≤0.04) better consistency than the modified dry one. Values of CVw for wet and modified dry blotting techniques ranged from 1.2% to 2.1% and from 3.7% to 5.4%, respectively. As for dry CL mass values, CVw values were not significantly different (P≥0.05) between wet (range: 1.1%-1.9%) and dry (range: 1.0%-5.1%) blotting techniques, except for Dailies AquaComfort Plus (P=0.03). Bland-Altman analysis showed poor agreement between the techniques. The wet blotting technique yielded WC values close (around 1%) to nominal ones, in contrast to modified dry blotting technique (≥2.5%). CONCLUSIONS: The wet blotting technique is not only more reliable than the modified dry one when obtaining hydrated CL mass but also provides more accurate nominal WC measurements. Agreement between the techniques was poor.

Comparison of specular microscopy and ultrasound pachymetry before and after cataract surgery.

PURPOSE: To compare specular microscopy (Topcon SP-3000P, Topcon Corporation, Tokyo, Japan) and ultrasound (US) technology when evaluating central corneal thickness (CCT) prior to and after phacoemulsification. METHODS: Corneal edema was assessed in phacoemulsification patients due to senile cataract by measuring CCT preoperatively and 1 day, 1 month, and 3 months postoperatively. Bland-Altman analysis was performed to assess interchangeability between pachymetry techniques for each visit. Repeated measures analysis of variance was performed to evaluate variation in CCT agreement depending on the degree of corneal edema. RESULTS: One hundred and eighteen patients aged 73.9 ± 10.1 years were recruited. Topcon SP-3000P provided significant (p < 0.0001) lower CCT values than US with and without induced corneal edema. Mean differences between CCT techniques for baseline, 1 day, 1 month and 3 months after cataract surgery were -28.9 ± 22.6, -30.5 ± 41.4, -32.3 ± 16.2 and -33.0 ± 16.9 µm, respectively. The systematic bias observed was not significantly different among the 4 visits (p = 0.59). The estimated limits of agreement (based on 1.96 standard deviation) were substantial, being 90.5, 165.8, 64.9 and 67.5 um at baseline, 1 day and 1 and 3 months. CONCLUSIONS: Topcon SP-3000P provides similar systematic bias in comparison with US technique for CCT measurements regardless of the degree of corneal edema after phacoemulsification, which should be reduced after applying a constant calibration adjustment of ∼30 µm. However, interchangeability between techniques may be still limited by the notable random measurement error.

Predictive models of long-term anatomic outcome in age-related macular degeneration treated with as-needed Ranibizumab.

BACKGROUND: To analyze predictors and develop predictive models of anatomic outcome in neovascular age-related macular degeneration (AMD) treated with as-needed ranibizumab after 4 years of follow-up. METHODS: A multicenter consecutive case series non-interventional study was performed. Clinical, funduscopic and OCT characteristics of 194 treatment-naïve patients with AMD treated with as-needed ranibizumab for at least 2 years and up to 4 years were analyzed at baseline, 3 months and each year until the end of the follow-up. Baseline demographic and angiographic characteristics were also evaluated. R Statistical Software was used for statistical analysis. Main outcome measure was final anatomic status. RESULTS: Factors associated with less probability of preserved macula were diagnosis in 2009, older age, worse vision, presence of atrophy/fibrosis, pigment epithelium detachment, and geographic atrophy/fibrotic scar/neovascular AMD in the fellow eye. Factors associated with higher probability of GA were presence of atrophy and greater number of injections, whereas male sex, worse vision, lesser change in central macular thickness and presence of fibrosis were associated with less probability of GA as final macular status. Predictive model of preserved macula vs. GA/fibrotic scar showed sensibility of 77.78% and specificity of 69.09%. Predictive model of GA vs. fibrotic scar showed sensibility of 68.89% and specificity of 72.22%. CONCLUSIONS: We identified predictors of final macular status, and developed two predictive models. Predictive models that we propose are based on easily harvested variables, and, if validated, could be a useful tool for individual patient management and clinical research studies.

Ocular response to environmental variations in contact lens wearers.

PURPOSE: To assess the influence of different indoor environments simulated in an environmental chamber on soft contact lens (CL) wearers. METHODS: Fifty-four CL wearers were grouped based on their symptoms while wearing their CLs. Subjects were fitted with two different CL types, conventional hydrogel (Omafilcon A) and silicone hydrogel (comfilcon A), and exposed to two controlled indoor environmental conditions, standard [50% relative humidity (RH), 23°C, 930 mb of atmospheric pressure] and adverse (in-flight air cabin environment: 5% RH, localised air flow, 23°C, 750 mb atmospheric pressure), for 90 min in an environmental chamber, making a total of four visits. Symptoms, tear osmolarity, pre-lens tear breakup time (PLBUT), phenol red thread test, visual acuity, bulbar and limbal hyperaemia, corneal and limbal staining, and CL dehydration were assessed using repeated measures analysis of variance. A linear mixed model was used to analyse the effect of environment, CL type, discomfort-based grouping, and time on blink rate. RESULTS: Environment was found to significantly (p ≤ 0.018) affect limbal and bulbar hyperaemia, PLBUT, tear osmolarity, and CL dehydration. Likewise, CL type significantly (p ≤ 0.04) affected nasal and total corneal staining, limbal conjunctival staining, CL dehydration, comfort, and blurred vision. The environment, CL type, and time had significant effects (p ≤ 0.0001) on the blink rate. CONCLUSIONS: Ocular surface integrity and blink rate in CL wearers depend on the environment CL users are exposed to, as well as on the soft CL type that they are wearing. Tight control of environmental conditions can contribute to a better understanding of CL-related discomfort.

Topical Fluorometholone Protects the Ocular Surface of Dry Eye Patients from Desiccating Stress: A Randomized Controlled Clinical Trial.

PURPOSE: To assess the efficacy of topical 0.1% fluorometholone in dry eye disease (DED) patients for ameliorating the worsening of the ocular surface when exposed to adverse environments. DESIGN: Single-center, double-masked, randomized, vehicle-controlled clinical trial. PARTICIPANTS: Forty-one patients showing moderate to severe DED. METHODS: Patients randomly received 1 drop 4 times daily of either topical 0.1% fluorometholone (FML group) or topical polyvinyl alcohol (PA group) for 22 days. Corneal and conjunctival staining, conjunctival hyperemia, tear film breakup time (TBUT), tear osmolarity, and the Symptom Assessment in Dry Eye (SANDE) questionnaire scores were determined at baseline. Variables were reassessed on day 21 before and after undergoing a 2-hour controlled adverse environment exposure and again on day 22. MAIN OUTCOMES MEASURES: Percentage of patients showing an increase 1 point or more in corneal staining and a reduction of 2 points or more (0-10 scale) in SANDE score, after the controlled adverse environment exposure and 24 hours later. RESULTS: After 21 days of treatment, the FML group showed greater improvements in corneal and conjunctival staining, hyperemia, and TBUT than the PA group (P≤0.03). After the adverse exposure, the percentage of patients having a 1-grade or more increase in corneal staining was significantly (P = 0.03) higher in the PA group (63.1% vs. 23.8%, respectively). Additionally, the FML group showed no significant changes in corneal staining (mean, 0.86; 95% confidence interval [CI], 0.47-1.25; vs. mean, 1.05; 95% CI, 0.59-1.51, for visit 2 and 3, respectively), conjunctival staining (mean, 0.95; 95% CI, 0.54-1.37 vs. mean, 1.19; 95% CI, 0.75-1.63), and hyperemia (mean, 0.71; 95% CI, 0.41-1.02 vs. 1.14; 95% CI, 0.71-1.58) after the exposure, whereas for the PA group, there was significant worsening (P≤0.009) in these variables (corneal staining: mean, 1.95; 95% CI, 1.57-2.33 vs. mean, 2.58; 95% CI, 2.17-2.98; conjunctival staining: mean, 1.68; 95% CI, 1.29-2.08 vs. mean, 2.47; 95% CI, 2.07-2.88; hyperemia: mean, 1.95; 95% CI, 1.63-2.26 vs. mean, 2.84; 95% CI, 2.62-3.07). CONCLUSIONS: Three-week topical 0.1% fluorometholone therapy is effective not only in reducing ocular surface signs in DED patients, but also especially in preventing exacerbation caused by exposure to a desiccating stress.

Vertical transmission of bacterial eye infections, Angola, 2011-2012.

To determine transmission rates for neonatal conjunctivitis causative microorganisms in Angola, we analyzed 312 endocervical and 255 conjunctival samples from mothers and newborns, respectively, during 2011-2012. Transmission rates were 50% for Chlamydia trachomatis and Neisseria gonorrhoeae and 10.5% for Mycoplasma genitalium. Possible pathogenic effects of M. genitalium in children's eyes are unknown.

Association between SNPs of Metalloproteinases and Prostaglandin F2α Receptor Genes and Latanoprost Response in Open-Angle Glaucoma.

PURPOSE: To determine whether single nucleotide polymorphisms (SNPs) of genes coding for matrix metalloproteinases (MMPs) and the prostaglandin F2α receptor gene (PTGFR) are related to a response to latanoprost in a white Spanish population of glaucomatous patients. DESIGN: Case-control study. PARTICIPANTS: One hundred twenty-four patients with open-angle glaucoma. METHODS: Genotyping was performed in 117 patients with primary open-angle glaucoma with a minimum treatment duration of 4 weeks. Candidate genes and individual polymorphisms were selected according to the effect on the mechanism of action of latanoprost. Multi-SNP haplotype analyses for associations also were tested. MAIN OUTCOME MEASURES: Diurnal intraocular pressure reduction and genotyping of the SNPs in the MMPs and PTGFR. RESULTS: The PTGFR SNPs were associated with positive (rs6686438, rs10786455) and negative (rs3753380, rs6672484, rs11578155) responses to latanoprost. Multiple testing found 2 genes, PTGFR and MMP-1, were related to refractoriness to latanoprost. CONCLUSIONS: The SNPs of the PTGFR and MMP-1 genes may determine the latanoprost response in a white European Spanish population. This study identified 5 SNPs related to the latanoprost response; 1 SNP, rs3753380, already has been associated with a poor response to latanoprost in a healthy Japanese population. Latanoprost is a commonly used antiglaucomatous drug, and increased knowledge of its mechanism of action will lead to advances in pharmacogenetics.

Intra- and inter-day variation of cytokines and chemokines in tears of healthy subjects.

Tear levels of certain cytokines/chemokines can potentially serve as biomarkers for dry eye and other ocular surface diseases if they remain stable from day-to-day in healthy eyes. The aim of this study was to determine the normal intra- and inter-day variation of selected tear cytokines/chemokines. Tear samples from 24 young, healthy adults were collected 11:00 AM-1:00 PM (mid-day) and 5:00-7:00 PM (evening) on three non-consecutive days. Concentrations of 18 cytokines/chemokines (EGF, eotaxin, CX3CL1/fractalkine, GM-CSF, IFN-γ, IL-10, IL-1ß, IL-13, IL-17A, IL-1RA, IL-5, IL-6, CXCL8/IL-8, IL-9, CXCL10/IP-10, CCL5/RANTES, TNF-α, and VEGF) were measured by multiplex bead analysis. Ocular surface disease was ruled out by clinical tests. A random-effects ANOVA model was used to evaluate intra- and inter-day effects on cytokine/chemokine levels. Repeatability of intra-subject inter-day measurements was assayed by coefficient of variation. Ten out of the 18 molecules had detectable tear levels in >50% of the subjects. Of those, only IL-10 and IL-1ß levels had significant inter-day variations. EGF, CX3CL1/fractalkine, CXCL10/IP-10, and VEGF were consistently higher in the evening compared to the mid-day measurements. EGF, CXCL10/IP-10, VEGF and CXCL8/IL-8had good intra-subject reproducibility. In conclusion, tear cytokines/chemokines can be measured reproducibly over time, with most not having significant inter-day variability. Some varied significantly depending upon the time of tear collection, and these variations should be taken into account when comparisons are made. The good intra-subject reproducibility for EGF, CXCL10/IP-10, CXCL8/IL-8, and VEGF indicates that these molecules could potentially serve as biomarkers of ocular surface disease.

Funduscopic results after 4-year follow-up treatment with ranibizumab for age-related macular degeneration in a region of Spain.

BACKGROUND: The study aims to survey longstanding funduscopic and functional outcomes of age-related macular degeneration (AMD) after ranibizumab treatment and verify the accuracy of a new method to compare the retinal thickness measured with different optical coherence tomography (OCT) tools. METHODS: Case series included 314 eyes with 2-4 years of follow-up. Main Outcome Measures were visual acuity (VA), number of injections, retinal thickness, OCT morphology, and final macular funduscopic status. RESULTS: One hundred twenty-two men and 177 women (mean age, 78.3 years) were included. The mean time to the first injection was 17.3 ± 14.6 days. Initial VA was O.8(20/125) ± 0.5; 0.7(20/100) ± 0.5 at 3 months; 0.8(20/125) ± 0.5 at a year; 1(20/200) ± 0.6 at year 2; 1(20/200) ± 0.6 at year 3 and 1.1(20/250) ± 0.6 at year 4. Number of visits at 3 months was 2.7 ± 0.8; 7.3 ± 2.1 at a year; 5.2 ± 2.7 along the 2nd year; 3.9 ± 2.3 at year 3 and 3.6 ± 2.2 at year 4. Number of injections at 3 months was 2.6 ± 0.5; 3.9 ± 1.5 at a year; 1.1 ± 1.5 along the 2nd year; 1.5 ± 2.4 at year 3 and 1.8 ± 3.1 at year 4. Patients with worse VA outcomes received more injections and were older. The formula to calculate changes in retinal thickness showed a 30% reduction in thickness, which correlated well with the OCT morphology. Patients with polypoidal choroidal vasculopathy (PCV) had a worse final outcome. The final disciform macular status (37%) was related to fewer injections and a greater decrease in thickness. Final well-preserved maculas (12.%) needed more injections and treatment changes; those that were atrophic at the final visit (30.8%) had a worse initial VA and greater decrease in thickness at the 3-month visit. CONCLUSIONS: Younger patients had better final outcomes. Our method to compare retinal thickness using different OCT tools worked well. The final visual outcome after a long follow-up was poor, which may be related to advanced age, poor initial VA, and the high incidence of final fibrosis or atrophy.