The field of RNAi therapeutics has quickly adapted to the treatment of ocular diseases. Although the eye provides a unique system for the delivery of siRNAs, its complex structure and composition fostered the development of novel strategies for efficient gene silencing in the target compartment. Moreover, anterior and posterior segments differ in their multiple drug barriers and clearance mechanisms. This chapter summarizes the recent achievements in terms of routes of administration, chemical modifications, and delivery systems for siRNAs that specifically apply to eye disorders. Methods employed for siRNA detection/quantitation in ocular tissues are also described, together with safety concerns that need to be addressed to fulfill regulatory requirements of new drug approval. Even though RNAi therapies for ocular diseases have not yet translated into patient care, we document herein the rising number of candidate drugs currently under preclinical or clinical development.

Background Glaucoma drainage device (GDD) implantation in the anterior chamber are associated with corneal complications. We describe a novel technique to implant GDD tubes in the posterior chamber of pseudophakic eyes. Methods Ten patients with glaucoma who required GDD tube implantation were included. Results The new technique begins with the passage of one of two straight needles existing at each end of a 10-0 Polypropylene suture through the GDD tube. A 23-gauge needle then is inserted at an angle 180 degrees away and passed from the anterior to the posterior chamber and finally through the sclera. The two suture straight needles from the 10-0 Polypropylene suture are positioned in the lumen of the 23-gauge needle. The 23-gauge needle is then extracted from the eye by passing the 2 needles through the lumen. The suture remains inside the posterior chamber, and the tube is inserted into the posterior chamber by pulling on the suture from the other side. No intra-operative complications were found such as bleeding, vitreous tube placement, bent tubes, etc. Conclusions This surgical procedure to implant a tube into the posterior chamber of the pseudophakic eyes is uncomplicated and facilitates the insertion of the flexible tube into the posterior chamber. This eliminates the tendency of the tube to enter the vitreous as the tube is always placed in the posterior chamber away from the cornea.

Purpose To analyse nocturnal intraocular pressure (IOP) fluctuations in patients with obstructive sleep apnea syndrome (OSAS) using a contact lens sensor (CLS) and to identify associations between the OSAS parameters determined by polysomnographic study (PSG) and IOP changes. Method Prospective, observational study. Twenty participants suspected of having OSAS were recruited. During PSG study, IOP was monitored using a CLS placed in the eye of the patient. The patients were classified according to the apnea-hypopnea index (AHI) in two categories, severe (> 30) or mild/moderate (< 30) OSAS. We evaluated several parameters determined by the IOP curves, including nocturnal elevations (acrophase) and plateau times in acrophase (PTs) defined by mathematical and visual methods. Results The IOP curves exhibited a nocturnal acrophase followed by PTs of varying extents at which the IOP remained higher than daytime measurement with small variations. We found significant differences in the length of the PTs in patients with severe OSAS compared to those with mild/moderate disease (P = 0.032/P = 0.028). We found a positive correlation between PTs and OSAS severity measured by the total number of apneic events (r = 0.681/ 0.751 P = 0.004/0.001) and AHI (r = 0.674/0.710, P = 0.004/0.002). Respiratory-related arousal and oxygen saturation also were associated significantly with the IOP PT length. Conclusions Periods of nocturnal IOP elevation lasted longer in severe OSAS patients than those with mild/moderate OSAS and correlate with the severity of the disease. The length of the nocturnal PT is also associated to respiratory parameters altered in patients with OSAS.

BackgroundTear film stability is the key event in ocular surface diseases. The purpose of this study is to evaluate spatial and temporal progression of the tear film breakup using an automatic non-invasive device.MethodsNon-invasive tear breakup time (NITBUT) parameters, such as First NITBUT (F-NITBUT) and Average NITBUT (A-NITBUT), were evaluated in 132 glaucoma and 87 control eyes with the Keratograph 5M device. Further analysis of this data was used to determine size, location and progression of tear film breakup with automatically identified breakup areas (BUA). The progression from First BUA (F-BUA) to total BUA (T-BUA) was expressed as Dry Area Growth Rate (DAGR). Differences between both groups were analysed using Student t-test for parametric data and Mann-Whitney U test for non-parametric data. Pearson's correlation coefficient was used to assess the relationship between parametric variables and Spearman in the case of non-parametric variables.ResultsF-NITBUT was 11.437.83s in the control group and 8.17 +/- 5.73 in the glaucoma group (P=0.010). A-NITBUT was 14.04 +/- 7.21 and 11.82 +/- 6.09s in control and glaucoma groups, respectively (P=0.028). F-BUA was higher in the glaucoma group than in the control group (2.73 and 2.28; P=0.022) and was more frequently located at the centre of the cornea in the glaucoma group (P=0.039). T-BUA was also higher in the glaucoma group than in the control group (13.24 and 9.76%; P=0.012) and the DAGR was steeper in the glaucoma group than in the control group (34.38 degrees and 27.15 degrees; P=0.009).Conclusions Shorter NITBUT values and bigger, more central tear film breakup locations were observed in the glaucoma group than in the control group. The DAGR indicates that tear film rupture is bigger and increases faster in glaucomatous eyes than in normal eyes.

Purpose To evaluate the quality of life of glaucoma patients using the Ocular Surface Disease Index (OSDI) questionnaire and their association with dry eye clinical signs. Methods The study included patients into three groups. The treated group diagnosed with bilateral open-angle glaucoma and treated with one or more topical medication at least 1 year. The operated group underwent glaucoma surgery without the need for topical medications. The control group entered subjects without ocular diseases or previous surgeries. Dry eye clinical signs were evaluated; noninvasive tear break-up time, Meibomian gland depletion (MGD), and conjunctival hyperemia were measured using the Keratograph 5 M. The total-OSDI (T-OSDI) score was divided into the visual field-OSDI and discomfort-OSDI scores. Results Two hundred and nine subjects participated in this cross-sectional study, 147 using glaucoma medications, 21 patients underwent glaucoma surgery and 41 were controls. The T-OSDI and subscores were higher in glaucoma patients compared with controls (p < 0.05); we found no differences between treated and surgically groups. Correlations were observed between the T-OSDI values and Schirmer test (p = 0.016), ocular surface staining (p < 0.001) and the MGD (p = 0.006). The subscores were associated with the ocular surface staining (VF p = 0.013 and D p = 0.003). In treated patients, the number of drops per day correlates with T-OSDI and subscores (p = 0.017 and p = 0.005). Conclusion OSDI scores increased in the glaucoma patients compared to controls without significant changes between treated and surgical patients. OSDI scores were associated to dry eye signs and medication in glaucoma patients.

Precis: Noninferiority of efficacy was demonstrated for a preservative- free latanoprost-timolol fixed combination compared with a BAK-containing formulation at 84 days after treatment in patients with open-angle glaucoma or ocular hypertension. Purpose: The purpose of this study was to compare the effect on intraocular pressure and safety of preservative-free latanoprosttimolol fixed combination (T2347) to benzalkonium chloride-preserved latanoprost-timolol fixed combination in patients with open-angle glaucoma or ocular hypertension. Methods: Phase III, randomized, parallel-group, investigatormasked study in 10 countries. A total of 242 patients aged 18 years or older with open-angle glaucoma or ocular hypertension in both eyes controlled with a preserved latanoprost-timolol fixed combination (15.7 +/- 2.4 mm Hg overall before inclusion) were randomized at day 0 with no washout period to receive the preservativefree alternative T2347 (N = 127) or remain on the preserved comparator (N= 115) for 84 days. Intraocular pressure changes from day 0 were measured at 9: 00 am (+/- 1 hour) on day 42 and day 84, and noninferiority of T2347 to the preserved comparator was analyzed statistically at day 84. Safety parameters were also reported. Results: The mean change in intraocular pressure from baseline to day 84 was -0.49 +/- 1.80mmHg for preservative-free T2347 and -0.49 +/- 2.25mmHg for the preserved comparator. These results met the noninferiority limits. Similar results were observed at day 42. There was no difference between groups in the incidence of adverse events or ocular signs. The total ocular symptoms score was better for T2347 than BPLT upon instillation at day 84 (45.9%/ 44.3%/9.8% of patients with improvement/no change/worsening vs. 33.6%/47.3%/19.1%; P= 0.021), reflecting improvements in individual symptoms such as irritation/burning/stinging (P< 0.001), and itching (P< 0.01) on day 84. Conclusions: Preservative-free latanoprost-timolol fixed combination T2347 showed noninferior efficacy compared with the preserved comparator and was well tolerated.

Purpose To report 1-year treatment outcomes of P50 EX-PRESS implant versus nonpenetrating deep sclerectomy (NPDS) with Esnoper V2000 combined with phacoemulsification. Design Randomized, prospective and multicentre clinical trial. Methods Settings: Six clinical centres. Population: Patients 54-89 years of age without previous filtering surgery with cataract and glaucoma who required lower levels of intraocular pressure (IOP). Interventions: Phaco-EX-PRESS P50 or Phaco-NPDS with Esnoper V2000, both groups with mitomycin C (0.2 mg/ml for 2 min). Main outcome measures: IOP, complete success rate (IOP: >= 6 and <= 18 mmHg), visual acuity, use of medical therapy and systematic assessment of complications and postoperative interventions. Results A total of 98 eyes were enrolled, including 50 in the EX-PRESS group and 48 in the NPDS group. At 12 months, IOP (mean +/- SD) was 13.9 +/- 3.3 mmHg in EX-PRESS group and 13.3 +/- 3.6 mmHg in NPDS group (p = 0.38). Success rate was 75% and 80% in EX-PRESS and NPDS groups, respectively (p = 0.53). The number of glaucoma medications (mean +/- SD) was 0.2 +/- 0.55 in EX-PRESS group and 0.17 +/- 0.44 in NPDS group (p = 1.00). The total number of complications was 66 in 35 subjects in EX-PRESS group and 39 in 23 subjects in NPDS group (p = 0.02). The incidence of more than one complication was n = 13 (26%) versus n = 9 (18.8%) in EX-PRESS and NPDS groups, respectively (p = 0.38). The total number of required postoperative interventions was 59 and 26 in EX-PRESS and NPDS groups, respectively (p = 0.01). Visual acuity was similar in both groups at month 12 (p = 0.13). Surgical time (mean +/- SD) was 52.6 +/- 13.6 min in EX-PRESS group and 63.3 +/- 19.4 min in NPDS group (p = 0.01). Conclusion Phaco-EX-PRESS surgery had similar success rate compared to Phaco-NPDS during 1 year of follow-up. Both procedures were associated with similar IOP reduction and use of additional medical therapy at 12 months. EX-PRESS surgery required more postoperative interventions and had more complications, but needed less surgical time compared to NPDS.

To evaluate automatic peripapillary choroidal thickness (PPCT) measurements in a wide area around the optic disc and various established zones in primary open-angle glaucoma (POAG) patients and age- and sex-matched healthy controls using a new swept-source optical coherence tomography (SS-OCT) device. Single center cross-sectional observational study. A total of 135 POAG patients and 86 healthy subjects were consecutively enrolled. An optic disc 6.0 x 6.0 mm three-dimensional scan OD was obtained using the SS-OCT Triton. A 26 x 26 cube-grid centered in the optic disc was generated to automatically measure choroidal thickness. Seven choroidal zones were established (superior temporal, central, and nasal; inferior temporal, central, and nasal, and the optic nerve head) and compared between healthy controls and POAG patients. PPCT was significantly thinner in the central superior, nasal superior, and nasal inferior zones of the POAG subjects. Choroidal thickness in the central superior zone was 124.61 +/- 54.95 A mu m in POAG group vs 156.17 +/- 80.89 A mu m in healthy controls (p = 0.029); in the nasal superior zone, 133.84 +/- 58.89 A mu m in the POAG group vs 168.34 +/- 73.45 A mu m in healthy controls (p = 0.012); and in the nasal inferior zone, 113.45 +/- 49.93 A mu m in the POAG group vs 137.47 +/- 65.96 A mu m in healthy controls (p = 0.049). Compared with healthy subjects, glaucoma patients present with peripapillary choroidal thinning, especially in the central superior, nasal superior, and nasal inferior zones. The new SS-OCT could be a useful tool to evaluate choroidal thinning, and it could be an additional support to facilitate glaucoma diagnosis.

Introduction: Dry eye disease (DED) is characterized by an alteration of the tear film with ocular inflammation and neurosensory abnormalities. The main clinical signs of this condition are tear instability and ocular damage. Although DED has gained significant attention in the past few years, limited prescription treatment options are available for patients.Areas covered: The current manuscript summarizes the pre-clinical and clinical development of tivanisiran, a novel small interfering oligonucleotide of RNA (siRNA) used for the treatment of DED. Tivanisiran was designed to silence Transient Receptor Potential Vanilloid 1 (TRPV1); herein the chemistry and mechanism of action of this new compound is also described.Expert opinion: Drugs currently on the market mostly target the inflammatory component of the disease and show only partial efficacy. New compounds addressing other aspects of the disease would provide significant advantages and contribute to a more personalized treatment of the disease. Tivanisiran has been designed to reduce ocular discomfort and pain, and was shown to improve ocular hyperemia and tear quality in human and animal models. Consequently, if the results of the ongoing and future clinical trials meet their study endpoints, tivanisiran could be submitted to obtain approval for the treatment of DED.

We demonstrated that the combined activation of PI3K/Akt and Smad2 results in in vitro expansion of phenotypic and functional CEC. Expanded cells were able to contribute to restoration of corneal endothelium in a rabbit model. These findings may represent a new therapeutic approach for treating corneal endothelial diseases

Purpose Previous studies have suggested that pregnancy may induce myopia progression. However, no longitudinal study with a large sample size and long-term follow-up has assessed this association. Our objective was to investigate whether pregnancy was related to mid-or long-term myopic refraction changes. Patients and methods A prospective study was conducted in a Mediterranean cohort. The study included 10 401 women (20-50 years old) from the SUN Project. SUN project is a multipurpose, prospective, and dynamic cohort of university graduates conducted in Spain. The recruitment of participants started in 1999 and it is permanently open. All participants in this cohort had university studies. Participants were followed up for a period of up to 14 years, and pregnancy and refractive changes were assessed through baseline and biennial questionnaires. Pregnancies and myopia were repeatedly assessed in each biennial follow-up questionnaire during a total of 14 years of follow-up. Results Pregnancy was inversely associated with the risk of myopia development or progression during each of the 2 years periods, with fully adjusted hazard ratio = 0.61; (95% confidence interval = 0.49-0.75) after adjusting for known potential confounders. Conclusion To our knowledge this is the first large-longitudinal assessment in young adult women, showing that pregnancy is inversely associated with myopia development or progression. Further studies are needed to confirm these epidemiological findings.

IMPORTANCE It is important to evaluate intraobserver and interobserver agreement using visual field (VF) testing and optical coherence tomography (OCT) software in order to understand whether the use of this software is sufficient to detect glaucoma progression and to make decisions regarding its treatment. OBJECTIVE To evaluate agreement in VF and OCT software among 5 glaucoma specialists. DESIGN, SETTING AND PARTICIPANTS The printout pages from VF progression software and OCT progression software from 100 patients were randomized, and the 5 glaucoma specialists subjectively and independently evaluated them for glaucoma. Each image was classified as having no progression, questionable progression, or progression. The principal investigator classified the patients previously as without variability (normal) or with high variability among tests (difficult). Using both software, the specialists also evaluated whether the glaucoma damage had progressed and if treatment change was needed. One month later, the same observers reevaluated the patients in a different order to determine intraobserver reproducibility. MAIN OUTCOMES AND MEASURES Intraobserver and interobserver agreement was estimated using. statistics and Gwet second-order agreement coefficient. The agreement was compared with other factors. RESULTS Of the 100 observed patients, half were male and all were white; the mean (SD) age was 69.7 (14.1) years. Intraobserver agreement was substantial to almost perfect for VF software (overall. [95% CI], 0.59 [0.46-0.72] to 0.87 [0.79-0.96]) and similar for OCT software (overall. [95% CI], 0.59 [0.46-0.71] to 0.85 [0.76-0.94]). Interobserver agreement among the 5 glaucoma specialists with the VF progression software was moderate (k, 0.48; 95% CI, 0.41-0.55) and similar to OCT progression software (k, 0.52; 95% CI, 0.44-0.59). Interobserver agreement was substantial in images classified as having no progression but only fair in those classified as having questionable glaucoma progression or glaucoma progression. Interobserver agreement was fair regarding questions about glaucoma progression (k, 0.39; 95% CI, 0.32-0.48) and consideration about treatment changes (k, 0.39; 95% CI, 0.32-0.48). The factors associated with agreement were the glaucoma stage and case difficulty. CONCLUSIONS AND RELEVANCE There was substantial intraobserver agreement but moderate interobserver agreement among glaucoma specialists using 2 glaucoma progression software packages. These data suggest that these glaucoma progression software packages are insufficient to obtain high interobserver agreement in both devices except in patients with no progression. The low agreement regarding progression or treatment changes suggests that both software programs used in isolation are insufficient for decision making.

Rationale: Erlotinib, an antineoplastic agent, is indicated for the treatment of patients with advanced nonsmall cell lung cancer. Most common adverse events are manageable, although more severe ones require dose reduction or discontinuation of erlotinib treatment. Patient concerns: We present a case of severe corneal ulcer treated with autologous plasma rich in growth factors. Diagnoses: A 76-year-old woman with stage IVB (cT2a N0 M1c) lung cancer under erlotinib treatment presented with rapidly progressing corneal ulcer. Evolution was torpid and refractory to conventional treatment. Interventions: Surgical options were dismissed because of the poor performance status of the patient. Despite temporary discontinuation of erlotinib treatment, the corneal ulcer continued to worsen with peripheral corneal neovascularization, stromal thinning, corneal edema, and profuse inflammation of the ocular surface. Outcomes: Treatment with autologous plasma rich in growth factors prevented an imminent corneal perforation and improved the corneal ulcer for over a year of follow-up. Lessons: Considering the poor results of conventional treatment, both medical and surgical, management of the inflammation of the ocular surface together with the stimulation of the healing processes through regenerative therapy such as PRGF, can be an option worth considering in these cases.

Smoking is a serious global public health concern that has been related to many chronic diseases. However, the effect of smoking on eye disorders has been less studied. The aim of this cohort study was to assess the association between current tobacco smokers and the risk of developing glaucoma and furthermore to evaluate the relationship between passive or former smokers and glaucoma. In this prospective and dynamic cohort, 16,797 participants initially who were found not to have glaucoma were followed up for a median of 8.5 years. Validated data on lifestyle, including tobacco consumption, were assessed at baseline. Information about new diagnosis of glaucoma was collected by follow-up questionnaires every 2 years. The outcome was the incidence of self-reported glaucoma during the follow-up. A subsample was used to validate the glaucoma diagnosis. During the 8.5 years of follow-up, 184 new glaucoma cases were identified. Current smokers had a significantly higher risk of glaucoma compared to participants who had never smoked after controlling for potential confounders (Hazard ratio [HR] 1.88 [95% coefficient interval (CI): 1.26-2.81]; P=0.002). A nonsignificant increased risk was found among former smokers (HR 1.27 [95% CI: 0.88-1.82]; P=0.198). When we assessed the exposure as per the number of cigarette pack-years, a dose-response relationship between pack-years and the risk of glaucoma was found (HR for the 5th quintile versus the 1st quintile: 1.70 [95% IC: 1.10-2.64], P for trend, 0.009). However, no relationship was found between passive smokers and glaucoma. (HR 0.67 [95% CI: 0.37-1.21]; P=0.189). Our results suggest a direct association between current smokers and the incidence of glaucoma. In particular, this association was related to the number of pack-years, which was not found in the case of former smokers nor in the case of passive smokers.

Smoking is a serious global public health concern that has been related to many chronic diseases. However, the effect of smoking on eye disorders has been less studied. The aim of this cohort study was to assess the association between current tobacco smokers and the risk of developing glaucoma and furthermore to evaluate the relationship between passive or former smokers and glaucoma.In this prospective and dynamic cohort, 16,797 participants initially who were found not to have glaucoma were followed up for a median of 8.5 years. Validated data on lifestyle, including tobacco consumption, were assessed at baseline. Information about new diagnosis of glaucoma was collected by follow-up questionnaires every 2 years. The outcome was the incidence of self-reported glaucoma during the follow-up. A subsample was used to validate the glaucoma diagnosis.During the 8.5 years of follow-up, 184 new glaucoma cases were identified. Current smokers had a significantly higher risk of glaucoma compared to participants who had never smoked after controlling for potential confounders (Hazard ratio [HR] 1.88 [95% coefficient interval (CI): 1.26-2.81]; P = 0.002). A nonsignificant increased risk was found among former smokers (HR 1.27 [95% CI: 0.88-1.82]; P = 0.198). When we assessed the exposure as per the number of cigarette pack-years, a dose-response relationship between pack-years and the risk of glaucoma was found (HR for the 5th quintile versus the 1st quintile: 1.70 [95% IC: 1.10-2.64], P for trend, 0.009). However, no relationship was found between passive smokers and glaucoma. (HR 0.67 [95% CI: 0.37-1.21]; P = 0.189).Our results suggest a direct association between current smokers and the incidence of glaucoma. In particular, this association was related to the number of pack-years, which was not found in the case of former smokers nor in the case of passive smokers.

Purpose: To determine variations in cytokine levels of glaucoma patients treated either with preservative-free latanoprost or preserved latanoprost, relative to healthy individuals. Methods: Tear samples were collected from 39 healthy subjects, 20 glaucoma patients treated with preserved latanoprost, and 20 patients treated with preservative-free latanoprost. A set of 27 inflammatory cytokines was analyzed in each group, including interleukin (IL)-1 beta, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor (FGF) basic, granulocyte colony stimulating factor (G-CSF), granulocyte monocyte colony stimulating factor (GM-CSF), interferon (IFN)-gamma, interferon gamma-induced protein (IP)-10, monocyte chemo attractant protein (MCP)-1MCAF, macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, platelet-derived growth factor (PDGF)-BB, regulated on activation, normal T cell expressed and secreted (RANTES), tumor necrosis factor (TNF)-alpha and vascular endothelial growth factor (VEGF). Cytokine concentrations were obtained by the Bio-Plex Human Cytokine Immunoassay. Non-invasive tear breakup time (NI-TBUT), tear meniscus height, corneal fluorescein staining, conjunctival hyperemia and ocular surface disease index (OSDI) were assessed in patients treated with preservative-free and preserved latanoprost. Results: The levels of IL-2, IL-5, IL-10, IL-12 (p70), IL-13, IL-15, IL-17, FGF basic, PDGF-BB, and TNF-alpha were significantly higher in patients receiving preserved latanoprost, compared to normal controls (p < 0.05). The expression of all the cytokines studied remained statistically invariable in patients receiving preservative-free latanoprost, compared to healthy subjects (p > 0.05). Ocular surface parameters were not significantly different in both glaucoma groups, and no correlation between these clinical parameters and cytokine levels was observed. Conclusions: Treatment with preserved latanoprost has a direct impact on tear cytokine levels, whereas this effect is not observed upon preservative-free latanoprost instillation.(C) 2017 Elsevier Inc. All rights reserved.

PURPOSE. To evaluate the efficacy and safety of SYL1001, a short interfering (si) RNA targeting the transient receptor potential cation channel subfamily V member 1 (TRPV1), for the treatment of dry eye disease (DED). METHODS. This study combines a phase I and two phase II clinical trials to test different doses of SYL1001 in a total of 156 healthy subjects and patients with DED. After 10 days of treatment, the primary efficacy endpoints were the effect on (1) the scoring in the Visual Analogue Scale (VAS) and Ocular Surface Disease Index (OSDI) questionnaires, and (2) ocular tolerance evaluated by corneal fluorescein staining and conjunctival hyperemia. Secondary endpoints included the assessment of systemic and local tolerance. RESULTS. Topical administration of SYL1001 1.125% once daily produced a significant decrease in VAS scores compared with placebo from day 4 until the end of treatment (change from baseline at day 10: -1.73 +/- 0.32 vs. -0.91 +/- 0.34; P = 0.013). For all treatments, OSDI scores were significantly reduced compared to their respective baseline values (P < 0.01), although no significant changes were detected between groups. Conjunctival hyperemia (quantified as normal or abnormal) significantly improved after instillation of SYL1001 1.125% compared with placebo (50% vs. 20%; P < 0.05). Excellent tolerability was reported, with no differences in the rates of occurrence of adverse events between groups. CONCLUSION. These trials achieved their primary endpoints of identifying the most effective dose of SYL1001 (1.125%). SYL1001 showed a large safety margin and may provide novel therapeutic opportunity for the relief of dry eye.

Objetivo: Evaluar la relación entre el tamaño del disco óptico y la medición de la Capa de Fibras Nerviosas de la Retina (CFNR) realizada por Cirrus OCT. Investigar su influencia en la capacidad diagnóstica. Diseño: Observacional, estudio transversal. Metodo: Se incluyeron 588 ojos (290 controles y 298 glaucomatosos). El tamaño del disco se determinó midiendo el diámetro vertical , horizontal y su área. En el grupo control, se evaluó la asociación entre la CFNR y el tamaño del disco mediante regresión lineal. El total de la muestra se dividió en cuartiles (área ¿1,56 mm2; 1.57-1.78 mm2; 1,79-2,08 mm2; ¿ 2,09 mm2), y se calcularon áreas bajo las curvas (AUC) ROC para cada grupo. Mediante el test de la t de Student para datos independientes se comparó el tamaño del disco entre ojos con diagnóstico incorrecto (falsos positivos ¿FP¿ y falsos negativos ¿FN¿) y correcto (verdaderos positivos -VP- y verdaderos negativos -VN-) Resultados: Para la medición de la CFNR media (Average), únicamente se encontró una correlación estadísticamente significativa (r=0,16, p=0,02) con el diámetro vertical. Sin embargo, para la medición en el cuadrante inferior, esta asociación también se vio con el área (r=0,13, p=0,03). Las mejores AUC se obtuvieron para el grupo 2 (áreas entre 1,57 -1,78 mm2) , (AUC: 0,89, IC95%: 0,82 a 0,93, p< 0,001, y AUC: 0,90, IC95%: 0,83 a 0,95, p< 0,001, Average e inferior, respectivamente). En los FN, los tamaños de disco fueron mayores que en los VN. Estas diferenci

Objective Many subjects, especially highly educated subjects, are increasingly exposed to computer use. This exposure might represent an explanation for the growing rates of myopia. Methods We assessed 17,217 Spanish university graduates from the SUN project, an open-recruitment cohort. Their mean age was 38.5 years (SD 12.1), and their mean time of exposure to computers was 14.3 h/week (SD 14.6). We estimated multivariable-adjusted odds ratios (OR) for the risk of myopia development and/or progression (¿ 0.5 diopters) according to baseline exposure to computer and to changes in exposure. Results The age and sex-adjusted OR comparing > 40 h/week of exposure versus < 10 h/week was 1.34 (95% confidence interval (CI): 1.12¿1.60). This association remained essentially unchanged after additional adjustments. Comparing participants who increased their exposure to computers, versus those with no change, the age and sex-adjusted OR was 1.49 (1.34¿1.66). This result was unchanged after additional adjustments. Conclusions To our knowledge this is the first large longitudinal assessment in young adults, showing that exposure to computer use is associated with myopia development or progression in a cohort of Spanish university graduates. Further studies are needed to confirm these epidemiological findings.

The objective of this study was to evaluate ocular tolerance, safety, and effect on intraocular pressure (IOP) of a topically administered small interfering RNA; SYL040012, on healthy volunteers. The study was an open-label, controlled, single-center study comprised of two intervals that enrolled 30 healthy subjects having IOP below 21 mmHg. SYL040012 was administered to one eye as a single dose to six subjects during interval 1. During interval 2 two different doses of SYL040012 were administered to one eye on a daily basis to two separate groups of 12 subjects each, over a period of 7 days. The contralateral eye was evaluated but not administered and served as control for the tolerance study. SYL040012 was well tolerated locally. No local or systemic adverse events related to the product developed in response to any of the doses studied. SYL040012 was not detected in plasma at any time point. Administration of SYL040012 over a period of 7 days reduced IOP values in 15 out of 24 healthy subjects regardless of the dose used. IOP decrease was statistically significant in response to one of the doses tested and responsiveness to SYL040012 seemed to be greater in individuals with higher baseline IOP.

AIM: To assess cultured limbal epithelial stem cell transplantation in patients with limbal stem cell deficiency by analyzing and quantifying corneal neovascularization. METHODS: This retrospective, interventional case series included eight eyes with total limbal stem cell deficiency. Ex vivo limbal epithelial stem cells were cultured on human amniotic membrane using an animal-free culture method. The clinical parameters of limbal stem cell deficiency, impression cytology, and quantification of corneal neovascularization were evaluated before and after cultured limbal stem cell transplantation. The area of corneal neovascularization, vessel caliber (VC), and invasive area (IA) were analyzed before and after stem cell transplantation by image analysis software. Best-corrected visual acuity (BCVA), epithelial transparency, and impression cytology were also measured. RESULTS: One year after surgery, successful cases showed a reduction (improvement) of all three parameters of corneal neovascularization [neovascular area (NA), VC, IA], while failed cases did not. NA decreased a mean of 32.31% (P=0.035), invasion area 29.37% (P=0.018) and VC 14.29% (P=0.072). BCVA improved in all eyes (mean follow-up, 76±21mo). Epithelial transparency improved significantly from 2.00±0.93 to 0.88±1.25 (P=0.014). Impression cytology showed that three cases failed after limbal epithelial stem cell therapy before 1y of follow-up. CONCLUSION: This method of analyzing and monitoring surface vessels is useful for evaluating the epithelial status during follow-up, as successful cases showed a bigger reduction in corneal neovascularization parameters than failed cases. Using this method, successful cases could be differentiated from failed cases.

The final incision size and the changes in incision size after IOL implantation were greater with the cartridge-insertion technique than with the wound-assisted technique. The increase was related to IOL spherical power in both groups but not to IOL toricity. Corneal biomechanical properties were not correlated with the final incision size

Purpose: The purpose of the study was to evaluate the influence of the examiner's experience on the reproducibility of retinal nerve fiber layer (RNFL) measurements obtained with Cirrus optical coherence tomography (OCT) and Stratus. Methods: Fifty-one normal and glaucomatous eyes of 51 participants were included. Two examiners (1 novice, 1 experienced) obtained 2 scans using both OCTs. For quantitative measurements, Bland and Altman limits of agreement were evaluated. For qualitative classifications, [kappa] coefficients were calculated. Results: Signal strength was higher with Cirrus than with Stratus (P<0.05). Signal strength was higher in scans performed by the experienced examiner than in those carried out by the inexperienced examiner in Stratus but not in Cirrus. RNFL measurement differences between Cirrus and Stratus were influenced by the examiner for the inferior (P=0.02), superior (P<0.001), and temporal quadrants (P=0.009). The RNFL quantitative agreement of examiners was higher in Cirrus than in Stratus. The qualitative agreement ([kappa] coefficients) of both examiners in the RNFL classification were almost perfect with Cirrus (in the average, superior, and inferior quadrants), and moderate with Stratus (only in average and inferior quadrant). Conclusions: The signal strength is independent of the examiner's experience in Cirrus but not in Stratus. RNFL measurements obtained by both examiners were more reproducible with Cirrus than with Stratus. The differences in RNFL measurements between both OCTs were related to the examiner's experience in all 3 quadrants. Agreement between operators in the RNFL classification was higher with Cirrus than Stratus.

Purpose To compare the intraocular pressures (IOPs) obtained with the IOPen rebound tonometer, Goldmann applanation tonometer (GAT) and the ocular response analyzer (ORA) and investigate the effects of corneal biomechanical properties on IOPen measurements. Methods A total of 198 normal eyes were included in this cross-sectional and randomized study. Three measurements were taken using IOPen. Agreement between tonometers was calculated using the Bland and Altman limits of agreement (LoA) analysis. Results The median IOPen IOP was 3¿mm¿Hg below the GAT (P<0.001), 3¿mm¿Hg below the ORA IOP similar to Goldmann (IOPg), and 3¿mm¿Hg below the ORA IOP corrected using corneal parameters (IOPcc)(P<0.01). The LoA width between the IOPen and GAT IOPs varied between 13.92 (mean IOPen IOP) and 15.99¿mm¿Hg (third IOPen measurement). The central corneal thickness (CCT) was unrelated to IOPen measurements (P>0.05). Corneal hysteresis (CH) and corneal rigidity factor (CRF) were correlated with IOPen and GAT. Conclusions IOPen underestimated the IOP compared with GAT and ORA. The effect of measurement quality or measurement order on IOPen was low. CCT did not affect the IOPen, but the CH and CRF did. The LoA width between the IOPen and GAT IOPs was higher than between the ORA IOPg or ORA IOPcc and GAT IOPs.

Purpose: To evaluate the frequency and characteristics of misalignments (MAs) in the retinal nerve fiber layer (RNFL) analysis protocol of spectral-domain optical coherence tomography (Cirrus) and determine factors associated with MAs. Methods: Three hundred eyes (162 normal and 138 glaucomatous eyes) were included in this cross-sectional study. The MAs were considered limited when they affected only part of the scan line, and complete (CMA) when they were observed in the entire scan line. A subgroup (153 cases) with repeated scans was analyzed to compare the RNFL thicknesses in the scans with and without CMAs. Results: Two hundred ninety-nine limited MAs were found in 140 eyes (46.7%) and 151 CMAs were found in 91 eyes (30.3%). The frequency and number of CMAs were significantly related to age (P<0.05). Seventy-two CMAs were in the measurement ring in 48 eyes, more frequently in the 3 and 9-o'clock positions (P=0.001) and the horizontal quadrants (P=0.001). Among the repeated scans, the number of cases with CMAs was similar to the first scan (P=0.32). No significant differences were found in global or quadrant RNFL thickness between scans with and without CMAs. Conclusions: CMAs were present in the first or second scans in about 30% of cases and were related to older age. CMAs were more frequently in horizontal meridians and quadrants. No differences in RNFL thickness were found between scans with and without CMAs in the same patients. Scans with CMAs in the measurement ring can be considered in the RNFL evaluation.

Purpose.: To compare the retinal nerve fiber layer (RNFL) evaluation using Cirrus optical coherence tomography (OCT) and Stratus OCT in glaucoma diagnosis. Methods.: One hundred thirty normal and 86 patients with glaucoma were included in this prospective study. The signal strengths of the OCTs were evaluated. The sensitivities and specificities of global RNFL average thickness were compared in the four quadrants and in each clock hour sector. Receiver operating characteristic (ROC) curves, areas under the ROC (AUC), and the likelihood ratio (LR) were plotted for RNFL thickness. Agreement between the OCTs was calculated by using the Bland-Altman method and kappa (¿) coefficient. Results.: Twenty-three percent of all cases examined with Stratus OCT and 1.9% examined with Cirrus OCT had a signal strength below 6 (P = 0.01). In cases with signal strengths ¿6, the mean signal strength was higher with Cirrus OCT than with Stratus OCT (P = 0.01). The RNFL measurements by Cirrus were thicker than those of Stratus OCT (P < 0.05). The AUCs were 0.829 for Stratus and 0.837 for Cirrus OCT (P = 0.706) for global RNFL average. LRs were similar in both OCTs in global RNFL classification but varied in quadrants. The widths of the limits of agreement varied between 42.16 and 97.79 ¿m. There was almost perfect agreement (¿ = 0.82) in the average RNFL classification. Conclusions.: Cirrus OCT has better scan quality than Stratus OCT, especially in glaucomatous eyes. In cases with good-quality scans, the sensitivity and specificity, and AUCs were similar. The best agreement was in the global average RNFL classification. The widths of limits of agreements exceed the limits of resolution of the OCTs.

A 46-year-old woman with moderate lens subluxation and Marfan¿s syndrome underwent a phacoemulsification on the right eye with a sutureless Henderson Capsular Tension Ring (HCTR) implantation. The surgical procedure and the postoperative follow up period were uneventful, with a best corrected visual acuity (BCVA) of 0 (LogMAR). Seven months after surgery the patient presented an inferomedial displacement of the HCTR due to contraction of the capsular bag, displacing the ring over the inferior haptic of the IOL that was pulled posteriorly beneath the equatorial area but remained centered. No further treatment was prescribed. The HCTR did not maintain an adequate capsular bag expansion and failed to redistribute tension from non-affected zonules over the areas of zonulysis. This case report raises the hypothesis that modified CTR¿s stiffness should be evaluated as an independent factor in the selection of a proper device for each patient.

Purpose. To estimate the prevalence and causes of bilateral blindness and visual impairment in an urban institutionalized population aged 65 years and older. Methods. A total of 392 nursing home residents completed a standardized eye examination, including measurement of visual acuity (VA), intraocular pressure, lens opacity grading, indirect ophthalmoscopy, and photography of the macular area. The major causes of vision loss identified for all participants were blindness and visual impairment. Results. The average subject age was 82 years (65¿97); women outnumbered men 263 to 129. The prevalence of bilateral blindness (VA ¿1.0 logarithm of the minimum angle of resolution [logMAR]) was 14.9% (43/288); the prevalence of visual impairment (VA ¿0.5 and 1.0 logMAR) was 31.9% (92/288). Blindness and visual impairment increased significantly with age (p<0.05), odds ratio (OR) 1.047 and 1.088, respectively. Cataract was the most common cause of bilateral blindness and visual impairment (27.9% and 44.6%, respectively) followed by pathologic myopia (23.3%) and age-related macular degeneration (AMD) (20.9%) for blindness, and by AMD (27.2%) and pathologic myopia (12%) for visual impairment. Fifty percent of subjects with visual loss had the potential for improved vision with medical or surgical intervention. Conclusions. Although the prevalences were high, these data are important since it is difficult for epidemiologic studies to include aged, institutionalized individuals, although their numbers are increasing. Recognition of the predominant causes of visual loss dependent on age is fundamental for early diagnosis and treatment of ocular diseases. Many cases of low vision can be treated with appropriate ophthalmologic care.