Technological advances in ocular trabecular meshwork in vitro models for glaucoma research.

Glaucoma is the leading cause of irreversible blindness worldwide and is characterized by the progressive degeneration of the optic nerve. Intraocular pressure (IOP), which is considered to be the main risk factor for glaucoma development, builds up in response to the resistance (resistance to what?) provided by the trabecular meshwork (TM) to aqueous humor (AH) outflow. Although the TM and its relationship to AH outflow have remained at the forefront of scientific interest, researchers remain uncertain regarding which mechanisms drive the deterioration of the TM. Current tissue-engineering fabrication techniques have come up with promising approaches to successfully recreate the TM. Nonetheless, more accurate models are needed to understand the factors that make glaucoma arise. In this review, we provide a chronological evaluation of the technological milestones that have taken place in the field of glaucoma research, and we conduct a comprehensive comparison of available TM fabrication technologies. Additionally, we also discuss AH perfusion platforms, since they are essential for the validation of these scaffolds, as well as pressure-outflow relationship studies and the discovery of new IOP-reduction therapies.

Ab interno implantation of glaucoma drainage devices tubes in the posterior chamber.

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° 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. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14276553 (31th May, 2019) Retrospectively registered.

Ocular surface analysis and automatic non-invasive assessment of tear film breakup location, extension and progression in patients with glaucoma.

BACKGROUND: Tear 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. METHODS: Non-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 5 M 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. RESULTS: F-NITBUT was 11.43 ± 7.83 s 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 ± 6.09 s 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° and 27.15°; 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.

Relationship between OSDI questionnaire and ocular surface changes in glaucomatous patients.

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.

The impact of computer use in myopia progression: a cohort study in Spain.

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 14.3h/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<10h/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.

Phase I clinical trial of SYL040012, a small interfering RNA targeting ß-adrenergic receptor 2, for lowering intraocular pressure.

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.

Intraocular lens dislocation and tube shunt in the posterior chamber: a case report.

BACKGROUND: To describe management of a case of intraocular lens (IOL) and capsular bag (CB) dislocation in an eye with an Ahmed glaucoma valve in the posterior chamber. CASE PRESENTATION: A 75-year-old pseudophakic man with open-angle glaucoma and diabetic retinopathy developed neovascular glaucoma. After two intravitreous injections of bevacizumab and panretinal photocoagulation were administered, the new vessels regressed. However, goniosynechiae were observed over 360° of the angle. An Ahmed glaucoma valve model FP7 was implanted with the tube in the posterior chamber with adequate intraocular pressure control. Nineteen years after cataract surgery, when the IOL-CB complex became dislocated, they were sutured transclerally to the sulcus without Ahmed glaucoma valve modification. After a coughing episode, the vitreous pushed the IOL-CB complex forward and the tube was behind the IOL-CB complex. A 25-gauge posterior vitrectomy was performed, and the tube was returned to in front of the optic of the IOL using a forceps tip through a sclerotomy. CONCLUSION: This case suggested that management of IOL-CB dislocation can modify glaucoma shunt function. A complete pars plana vitrectomy may be required in order to reposition the dislocated IOL-CB complex in the presence of a posterior chamber drainage tube implant.

A comparison of false positives in retinal nerve fiber layer, optic nerve head and macular ganglion cell-inner plexiform layer from two spectral-domain optical coherence tomography devices.

BACKGROUND: The incidence of false positive (FP) results of optic coherence tomography (OCT) retinal nerve fiber layer (RNFL) color code in healthy subjects can be very high with Cirrus OCT. Recent evidence has shown that OCT parameters derived from macular ganglion cell-inner plexiform layer (GCIPL) have excellent ability to discriminate between normal eyes and eyes with early glaucoma. METHODS: This was a prospective, cross-sectional study. One hundred eyes from 50 healthy volunteers underwent circumpapillary scanning by Cirrus and Spectralis OCT and macular scanning using Cirrus OCT. FP rates for each of the OCT parameters, using predefined criteria for an abnormal test were calculated. Comparative analysis was performed using the McNemar test. A generalized estimating equations model (GEE) was used to compare demographic and clinical factors between the eyes with normal findings and eyes with abnormal results. RESULTS: The overall RNFL color-code FP rate was significantly higher for Cirrus (39 %) than for Spectralis (18 %) (P = 0.000). The Spectralis RNFL FP rate showed no significant difference when compared to the FP rate by Cirrus GCIPL (13 %) and ONH (11 %) analysis. Axial length, mean spherical equivalent, presence of peripapillary atrophy, and tilted disc were significantly related to the RNFL FP occurrence displayed by both devices. CONCLUSIONS: Spectralis might be more specific than Cirrus when evaluating the RNFL thickness for Caucasians and moderate myopic population. GCIPL and ONH analysis might be more useful than RNFL thickness to evaluate this population using Cirrus OCT.

Artificial Trabecular Meshwork Structure Combining Melt Electrowriting and Solution Electrospinning.

The human trabecular meshwork (HTM) is responsible for regulating intraocular pressure (IOP) by means of gradient porosity. Changes in its physical properties, like increases in stiffness or alterations in the extracellular matrix (ECM), are associated with increases in the IOP, which is the primary cause of glaucoma. The complexity of its structure limits the engineered models to one-layered and simple approaches, which do not accurately replicate the biological and physiological cues related to glaucoma. Here, a combination of melt electrowriting (MEW) and solution electrospinning (SE) is explored as a biofabrication technique used to produce a gradient porous scaffold that mimics the multi-layered structure of the native HTM. Polycaprolactone (PCL) constructs with a height of 20-710 µm and fiber diameters of 0.7-37.5 µm were fabricated. After mechanical characterization, primary human trabecular meshwork cells (HTMCs) were seeded over the scaffolds within the subsequent 14-21 days. In order to validate the system's responsiveness, cells were treated with dexamethasone (Dex) and the rho inhibitor Netarsudil (Net). Scanning electron microscopy and immunochemistry staining were performed to evaluate the expected morphological changes caused by the drugs. Cells in the engineered membranes exhibited an HTMC-like morphology and a correct drug response. Although this work demonstrates the utility of combining MEW and SE in reconstructing complex morphological features like the HTM, new geometries and dimensions should be tested, and future works need to be directed towards perfusion studies.

Is Ultra-Processed Food Intake Associated with a Higher Risk of Glaucoma? A Prospective Cohort Study including 19,255 Participants from the SUN Project.

OBJECTIVE: The aim of this study was to examine the relationship of ultra-processed food (UPF) intake with the incidence of glaucoma in a large sample of Spanish university graduates followed prospectively. METHODS: Prospective cohort study using data from the SUN Project. A final sample of 19,225 participants (60.1% women) was included in this study, with a mean age of 38.2 years (standard deviation (SD) = 12.4). Participants were followed-up for a mean time of 12.9 years (SD = 5.4). Dietary intake was measured using a 136-item semiquantitative food-frequency questionnaire. UPFs were defined based on the NOVA classification system. Glaucoma diagnosis was determined by asking the participants if they had ever been diagnosed with glaucoma by an ophthalmologist. This self-reported diagnosis of glaucoma has been previously validated. RESULTS: After adjusting for several covariates, participants with the highest UPF consumption were at higher risk of glaucoma (hazard ratio (HR) = 1.83; 95% confidence interval (CI) 1.06 to 3.17) when compared to participants in the lowest category of UPF consumption. Regarding subgroup analyses, a significant multiplicative interaction was found for age (p = 0.004) and omega 3:6 ratio (p = 0.040). However, an association between UPF consumption and glaucoma was only found in older participants (aged ≥ 55 years), in men, in the most physically active group, in the group of non- or former smokers, in those with a lower omega 3:6 ratio, and in those with a lower energy intake. Regarding the contribution of each type of UPF group, UPF coming from sweets showed a significant risky effect (HR = 1.51; CI 95% 1.07 to 2.12). CONCLUSIONS: This prospective cohort study shows that participants with a greater UPF consumption have a higher risk of developing glaucoma when compared to participants with a lower consumption. Our findings emphasize the relevance of monitoring and limiting the consumption of UPFs as a means of preventing glaucoma incidence.

Nanofibrous PCL-Based Human Trabecular Meshwork for Aqueous Humor Outflow Studies.

Primary open-angle glaucoma is characterized by the progressive degeneration of the optic nerve, with the high intraocular pressure (IOP) being one of the main risk factors. The human trabecular meshwork (HTM), specifically the juxtacanalicular tissue (JCT), is responsible for placing resistance to the aqueous humor (AH) outflow and the resulting IOP control. Currently, the lack of a proper in vitro JCT model and the complexity of three-dimensional models impede advances in understanding the relationship between AH outflow and HTM degeneration. Therefore, we design an in vitro JCT model using a polycaprolactone (PCL) nanofibrous scaffold, which supports cells to recapitulate the functional JCT morphology and allow the study of outflow physiology. Mechanical and morphological characterizations of the electrospun membranes were performed, and human trabecular meshwork cells were seeded over the scaffolds. The engineered JCT was characterized by scanning electron microscopy, quantitative real-time polymerase chain reaction, and immunochemistry assays staining HTM cell markers and proteins. A pressure-sensitive perfusion system was constructed and used for the investigation of the outflow facility of the polymeric scaffold treated with dexamethasone (a glucocorticoid) and netarsudil (a novel IOP lowering the rho inhibitor). Cells in the in vitro model exhibited an HTM-like morphology, expression of myocilin, fibronectin, and collagen IV, genetic expression, outflow characteristics, and drug responsiveness. Altogether, the present work develops an in vitro JCT model to better understand HTM cell biology and the relationship between the AH outflow and the HTM and allow further drug screening of pharmacological agents that affect the trabecular outflow facility.

Comparison of Transcriptomic Analysis of the Conjunctiva in Glaucoma-Treated Eyes with Dry Eyes and Healthy Controls.

Ocular surface disease (OSD) associated with topical glaucoma drugs is a common issue impacting treatment adherence. We aimed to identify conjunctival transcriptomic changes in glaucoma and dry eye patients, comparing them to healthy controls. Bulbar conjunctival specimens were collected via impression cytology from 33 patients treated for glaucoma, 9 patients with dry eye, and 14 healthy controls. RNA extraction and bulk RNA sequencing were performed, followed by bioinformatics analysis to detect gene dysregulation. Ingenuity pathways analysis (IPA) identified pathways and biological processes associated with these transcriptomic changes. Sequencing analysis revealed 200 modified genes in glaucoma patients compared to healthy individuals, 233 differentially expressed genes in dry eye patients versus controls, and 650 genes in treated versus dry eye samples. In glaucoma patients, 79% of altered pathways were related to host defense, while dry eye patients showed a 39% involvement of host response, 15% in cellular proliferation and integrity, and 16% of mitochondrial dysfunction. These findings were validated through qRT-PCR. Glaucoma patients showed an intensified conjunctival immune response as a potential cause of OSD, whereas in dry eye patients, in addition to the immune response, other mechanisms such as mitochondrial dysfunction or reduced cellular proliferation were observed.

Changes in ocular surface after withdrawal of anti-glaucoma medications following non-penetrating deep sclerectomy.

Purpose: : To analyze the ocular surface changes in eyes after the withdrawal of anti-glaucomatous drugs when non-penetrating deep sclerectomy (NPDS) is performed. Methods: Thirty-one patients (33 eyes) diagnosed with glaucoma that underwent NPDS were included in this prospective study. The control group included 33 eyes. Four variables were studied using Keratograph 5M (K5M): ocular hyperemia (OH), non-invasive tear film break-up time (NI-BUT), lower tear meniscus height (LTMH), and meibography. LTMH was also measured using the anterior segment module of a Spectralis Fourier-domain optical coherence tomography (FD-OCT) instrument. Moreover, an evaluation of corneal and conjunctival staining was performed. In the glaucoma group, five visits were carried out: pre-surgery, 1 week after surgery, and 1 month, 3 months, and 6 months after surgery. In control groups, examinations were performed in only one visit. In addition, patients were asked to answer two questionnaires: Ocular Surface Disease Index (OSDI) and National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) before and 6 months after surgery. Results: Before NPDS, eyes showed worse objective data than healthy control subjects (P ≤ 0.049). In this group, a significant improvement was observed in questionnaire responses (P < 0.001), LTMH-FD-OCT (P = 0.037), LTMH-K5M (P = 0.025), K5M-OH (P = 0.003), NI-BUT (P = 0.022), and conjunctival and corneal staining (P < 0.001). No significant differences were observed between groups in FD-OCT and K5M LTMH, NI-BUT, corneal-conjunctival staining, nor in the most OH sector values at 6 months (P ≥ 0.62). Conclusion: A significant improvement in the ocular surface was observed 6 months after NPDS, suggesting that the withdrawal of the topical anti-glaucomatous treatment had a beneficial effect on the subjects.

ACE-Vitamin Index and Risk of Glaucoma: The SUN Project.

BACKGROUND: Previous studies regarding antioxidant consumption and glaucoma have shown contradictory results. The aim of this study was to analyze the combined effect of the consumption of three vitamins (A, C and E) on the incidence of glaucoma in the SUN Project. METHODS: For this study, 18,669 participants were included. The mean follow-up was 11.5 years. An index including vitamins A, C and E (ACE-Vitamin Index) was calculated. Vitamin intake was extracted from participants' dietary data and vitamin supplements, if taken. Information on glaucoma incidence was collected by previously validated self-reported questionnaires. The association between glaucoma and vitamin intake was assessed by repeated-measures Cox regression using multi-adjusted hazard ratios. RESULTS: A total of 251 (1.3%) cases of glaucoma were detected. Participants with a higher ACE-Vitamin Index presented a reduced risk of glaucoma compared to participants with lower consumption (adjusted HR = 0.73; 95% CI, (0.55-0.98)). When each vitamin was analyzed individually, none of them had a significant protective effect. The protective effect of the ACE-Vitamin Index was higher in men and older participants (≥55 year). CONCLUSIONS: The consumption of vitamins A, C and E considered separately do not seem to exert a protective effect against glaucoma, but when these vitamins are considered together, they are associated with a lower risk of glaucoma.

External Validation and Clinical Applicability of Two Optical Coherence Tomography-Based Risk Calculators for Detecting Glaucoma.

Purpose: To clinically validate the diagnostic ability of two optical coherence tomography (OCT)-based glaucoma diagnostic calculators (GDCs). Methods: We conducted a retrospective, consecutive sampling of 76 patients with primary open-angle glaucoma, 107 glaucoma suspects, and 67 controls. Demographics, reliable visual field testing, and macular and optic disc OCT were collected. The reference diagnosis was compared against the probability of having glaucoma obtained from two GDCs derived from multivariate logistic regressions using quantitative and qualitative (GDC1) or only quantitative (GDC2) OCT data. The discrimination (area under the curve [AUC]) and calibration (calibration plots) were compared for both calculators and the best OCT parameters. Results: GDC2 was able to identify 46.9% more suspects and 14.7% more glaucomatous eyes than GDC1. Both GDCs obtained the highest discriminative ability in glaucomatous eyes (GDC1 AUC = 0.949; GDC2 = 0.943 vs inferior peripapillary retinal nerve fiber layer [pRNFL] = 0.931; P = 0.43). The discriminating ability was not as good for glaucoma suspects, but the GDCs were not inferior to pRNFL (GDC 1 AUC = 0.739; GDC2 = 0.730; inferior pRNFL = 0.760; P = 0.54) and GDC2 was still able to correctly identify up to 30.8% more cases than the conventional OCT classification. Calibration showed risk underestimation for both groups and calculators, but it was better in GDC2 and in patients with glaucoma. Conclusions: OCT-based calculators showed an excellent diagnostic performance in glaucomatous eyes. GDC2 was able to identify approximately 30% more cases than the conventional pRNFL inferior OCT classification in both groups, suggesting a potential role of these composite scores in clinical practice. Translational Relevance: These OCT-based calculators may improve glaucoma diagnosis in clinical care.

Healthy Lifestyle Score and Incidence of Glaucoma: The Sun Project.

BACKGROUND: The relationship between modifiable risk factors, such as diet and lifestyle, and glaucoma remains controversial. We analyse the effect of the Mediterranean lifestyle (ML) on glaucoma incidence in the "Seguimiento Universidad de Navarra" (SUN) Project. METHODS: The SUN Healthy Lifestyle Score (SHLS) includes 10 healthy habits: never having smoked, moderate to high physical activity, Mediterranean diet adherence, moderate alcohol consumption, low television exposure, no binge drinking, short afternoon napping, meeting up with friends, working at least 40 h/wk, and low body mass index. The information was collected biennially through self-reported questionnaires. The relationship between new glaucoma cases and the SHLS was assessed by Cox regression using hazard ratios. Crude, multi-adjusted, and sensitivity analyses were performed. RESULTS: During a median of 12 years of follow-up, 261 (1.42%) new cases of glaucoma were identified among 18,420 participants. After adjusting for potential confounders, participants in the healthiest SHLS category showed a significantly reduced risk of glaucoma compared to those in the lowest SHLS category (adjusted HR = 0.51, 95% CI = 0.28-0.93). For each point added to the SHLS, the risk of glaucoma relatively dropped 5%. CONCLUSIONS: Higher adherence to a ML, measured by the SHLS, was significantly associated with a lower risk of developing glaucoma. Based on our study, the ML is a protective factor for glaucoma incidence.

siRNA Therapeutics in Ocular Diseases.

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.

The influence of alcohol intake in myopia development or progression: The SUN cohort study.

BACKGROUND: Myopia is a highly prevalent disorder, and one of the first causes of blindness. In turn, alcohol consumption has been shown to be a risk factor for many diseases and a main contributor to the global burden of disease. However, no studies have investigated the relationship between alcohol intake and myopia. Our aim was to prospectively assess the association between alcohol intake and the development or progression of myopia. METHODS: In a Spanish dynamic prospective cohort (the SUN Project) we assessed 15,642 university graduates, recruited between 1999 and 2018 and followed up biennially through mailed questionnaires. Alcohol intake was assessed with a validated 136-item food frequency questionnaire. Development or progression of myopia was collected in subsequent questionnaires during follow-up every two years. RESULTS: Alcohol intake was linearly and significantly associated with a higher risk of myopia development or progression: the OR for 10-year incidence/progression of myopia was 1.05, 95% CI 1.01-1.09 per each 10-grams increase in alcohol intake. CONCLUSIONS: Alcohol consumption might lead to the development or progression of myopia, although confirmation is needed for the mechanisms through which this association may occur, thus further research is needed to verify these findings.

Carbohydrate intake and risk of glaucoma in the sun cohort.

PURPOSE: To assess the association between carbohydrates (CH) intake and glaucoma incidence. METHODS: 18,247 volunteer participants (183,067 person-years at risk) with 10-year of median follow-up were included in this prospective dynamic cohort. Baseline total CH intake (g/d) was categorised in quartiles and classified in nine different CH food sources. Self-reported diagnosis of glaucoma was collected at baseline and on biennial follow-up questionnaires. CH intake and glaucoma diagnosis were validated in a subsample of participants. We studied potential confounders and effect modificators, including diabetes. The relationship between CH intake and glaucoma incidence was analysed using multivariable Cox proportional hazards ratio (HR) models to adjust for potential confounding factors. RESULTS: During 10 years of median follow-up, a total of 242 new cases of glaucoma were identified. Participants in the highest quartile of baseline CH intake had a significantly higher risk of glaucoma as compared to participants in the lowest quartile [HR 1.50 (95% Confidence interval (CI): 1.01-2.25), p for trend = 0.042]. None of the nine CH food groups was individually related to glaucoma. In stratified analyses, after excluding all cases of diabetes, the HR comparing extreme quartiles of CH intake was 1.77 (95% CI: 1.15-2.74). CONCLUSIONS: Our results suggest that a higher intake of total carbohydrates is associated with a higher risk of incident glaucoma. The total amount of CH, rather than the specific food sources of CH, seems to play a major role, and this association does not seem to be confounded or modified by diabetic status.