Preventable risk factors for type 2 diabetes can be detected using noninvasive spontaneous electroretinogram signals.

Given the ever-increasing prevalence of type 2 diabetes and obesity, the pressure on global healthcare is expected to be colossal, especially in terms of blindness. Electroretinogram (ERG) has long been perceived as a first-use technique for diagnosing eye diseases, and some studies suggested its use for preventable risk factors of type 2 diabetes and thereby diabetic retinopathy (DR). Here, we show that in a non-evoked mode, ERG signals contain spontaneous oscillations that predict disease cases in rodent models of obesity and in people with overweight, obesity, and metabolic syndrome but not yet diabetes, using one single random forest-based model. Classification performance was both internally and externally validated, and correlation analysis showed that the spontaneous oscillations of the non-evoked ERG are altered before oscillatory potentials, which are the current gold-standard for early DR. Principal component and discriminant analysis suggested that the slow frequency (0.4-0.7 Hz) components are the main discriminators for our predictive model. In addition, we established that the optimal conditions to record these informative signals, are 5-minute duration recordings under daylight conditions, using any ERG sensors, including ones working with portative, non-mydriatic devices. Our study provides an early warning system with promising applications for prevention, monitoring and even the development of new therapies against type 2 diabetes.

A phase II randomized trial to evaluate the long-term (12-week) efficacy and safety of OC-01 (varenicline solution) nasal spray for dry eye disease: The MYSTIC study.

PURPOSE: Dry eye disease is characterized by loss of tear film stability. OC-01 (varenicline solution) is a small-molecule nicotinic acetylcholine receptor agonist administered as a nasal spray that stimulates tear production. METHODS: In MYSTIC (NCT03873246) patients aged ≥22 years with dry eye disease were randomized 1:1:1 to OC-01 0.03 mg, OC-01 0.06 mg, or vehicle (n = 41 per group), administered twice daily via intranasal spray, for 12 weeks (84 days). Primary efficacy endpoint was mean change from baseline in anesthetized Schirmer's test score (STS) in study eye at day (D) 84. RESULTS: Patients receiving OC-01 0.03 and 0.06 mg had statistically significantly increased tear production at D84 versus vehicle; least squares mean changes from baseline in STS were 10.8 mm and 11.0 mm for OC-01 0.03 and 0.06 mg, respectively. A trend toward a higher proportion of patients experiencing ≥10-mm improvement in STS from baseline was observed with OC-01 0.03 mg (36.6%; p > 0.05), and was significant for OC-01 0.06 mg (48.8%; p = 0.024), versus vehicle (24.4%). Non-ocular treatment-emergent adverse events (TEAEs) were reported by 21 patients; the most common was sneezing (OC-01 0.03 mg, 2 [4.9%]; OC-01 0.06 mg, 3 [7.3%]), with similar frequencies between treatment groups. No severe or serious TEAEs were reported. CONCLUSIONS: OC-01 (varenicline solution) nasal spray improved tear production in patients with dry eye disease over a long-term (12-week) period, and represents a receptor neuro-activator with a nasal route of administration that spares the ocular surface to stimulate tear production.

Safety and efficacy of lotilaner ophthalmic solution, 0.25% for the treatment of blepharitis due to demodex infestation: A randomized, controlled, double-masked clinical trial.

PURPOSE: To evaluate the safety and efficacy of lotilaner ophthalmic solution, 0.25% for the treatment of blepharitis due to Demodex infestation compared to vehicle control. METHODS: In this phase II, randomized, controlled, double-masked clinical trial, 60 eligible participants with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either topical lotilaner ophthalmic solution, 0.25% (Tarsus Pharmaceuticals, Inc., Irvine, CA) (study group) or the vehicle without lotilaner (control group) bilaterally twice a day for 28 days. Participants were followed at Days 7, 14, 28, 60 and 90. The efficacy parameters were change in collarette grade and Demodex density at Day 28. Safety parameters were adverse events, changes in corrected distance visual acuity (CDVA), intraocular pressure (IOP) and slit-lamp biomicroscopy. RESULTS: The study group showed a statistically significant decrease in collarette grade compared to the control group beginning at Day 14 (p = 0.003) in the upper eyelid and at Day 28 (p = 0.003) in the lower eyelid. Decreases in both lids were maintained through Day 90 (p < 0.001). At Day 28, mite eradication was achieved in 66.7% and 25.9% of eyes in the study and control group (p = 0.005); at Day 90, these proportions were 68.2% and 18.5% (p = 0.001), respectively. No serious adverse events or clinically significant changes in CDVA and IOP were observed. CONCLUSION: For Demodex blepharitis, treatment with lotilaner ophthalmic solution, 0.25% for 4 weeks is safe and effective. The improvement in collarette grade and mite density observed during the treatment period persisted for at least two months following treatment cessation.

Safety and Efficacy of Topical Lotilaner Ophthalmic Solution 0.25% for the Treatment of Demodex Blepharitis: A Pilot Study.

PURPOSE: Evaluate safety and efficacy of topical lotilaner ophthalmic solution, 0.25% for the treatment of Demodex blepharitis. Patients and Methods. 15 patients with Demodex blepharitis, defined as >10 collarettes on the upper lid, lid margin erythema, and Demodex density of ≥1.5 mites/lash on microscopy, were treated bid for 28 days with lotilaner ophthalmic solution, 0.25%. Contact lens wear, artificial eyelashes, and lid structural abnormalities were among the exclusion criteria. No other antibacterial, antiparasitic, or anti-inflammatory treatment or lid hygiene products were permitted. Patients were assessed on Days 7, 14, 28, 60, and 90. Outcome measures were changes in collarette grade and mite density on Day 28. Adverse events and changes in intraocular pressure (IOP), corrected distance visual acuity (CDVA), and slit-lamp biomicroscopy were assessed. RESULTS: Mean collarette grade (upper lids) improved from 3.07 ± 0.21 to 0.79 ± 0.19 on Day 28; the change was statistically significant for both upper and lower lids from Day 14 on. Mean mite density per lash decreased from 2.28 ± 0.16 at baseline to 0.14 ± 0.05 at Day 28 (p < 0.0001). Mite eradication (0 mites) was documented in 57.1% of eyes. The effects were durable through Day 90. There were no adverse events and little to no change in CDVA or IOP. The drop was well tolerated, with no discontinuations due to ocular irritation. CONCLUSION: Topical lotilaner ophthalmic solution, 0.25% for 4 weeks, showed promising efficacy for the treatment of Demodex blepharitis. This novel treatment appears to be safe and well tolerated. Randomized controlled studies are needed to confirm the results.

Collarette Elimination and Demodex Mite Eradication with Topical Lotilaner Ophthalmic Solution, 0.25.

Purpose: To evaluate the efficacy of topical lotilaner ophthalmic solution, 0.25%, in patients with Demodex blepharitis. Methods: Eighteen adults with Demodex blepharitis, defined as >10 collarettes on the upper lid and/or mite density of ≥1.5 mites per lash (upper and lower), were treated bid for 42 days with the topical lotilaner ophthalmic solution, 0.25%. Contact lens wear, artificial eyelashes, and lid structural abnormalities were among the exclusion criteria. No other antibacterial, antiparasitic, or anti-inflammatory treatment or lid hygiene products were permitted. One eye of each patient was selected for analysis and assessed on day 7, 14, 28, and 42. Collarettes were graded at each visit, and mite density was evaluated by microscopy at each visit except day 7. Outcome measures were collarette elimination (≤2 lashes with collarettes) and mite eradication (0 mites). Drop tolerability, adverse events, visual acuity, and slit-lamp biomicroscopy were assessed. Results: Collarette elimination was achieved in 13/18 participants (72.2%) by day 42. Mean collarette grade (upper lid) declined from 3.56 ± 0.17 to 0.28 ± 0.11. Mite eradication was achieved in 14/18 participants (77.8%) by day 42. Mean mite density decreased from 2.63 ± 0.39 to 0.12 ± 0.08 mites/lash. Participants reported good tolerability. Adverse events were mild and transient and did not result in treatment discontinuation. Conclusion: Six weeks of at-home topical therapy with the lotilaner ophthalmic solution, 0.25%, was effective in eliminating the most common objective signs of Demodex blepharitis, with a collarette elimination rate of 72% and mite eradication in 78% of eyes by day 42. ISRCTN registration #: 24398865.

Screening Diabetic Retinopathy Using an Automated Retinal Image Analysis System in Independent and Assistive Use Cases in Mexico: Randomized Controlled Trial.

BACKGROUND: The automated screening of patients at risk of developing diabetic retinopathy represents an opportunity to improve their midterm outcome and lower the public expenditure associated with direct and indirect costs of common sight-threatening complications of diabetes. OBJECTIVE: This study aimed to develop and evaluate the performance of an automated deep learning-based system to classify retinal fundus images as referable and nonreferable diabetic retinopathy cases, from international and Mexican patients. In particular, we aimed to evaluate the performance of the automated retina image analysis (ARIA) system under an independent scheme (ie, only ARIA screening) and 2 assistive schemes (ie, hybrid ARIA plus ophthalmologist screening), using a web-based platform for remote image analysis to determine and compare the sensibility and specificity of the 3 schemes. METHODS: A randomized controlled experiment was performed where 17 ophthalmologists were asked to classify a series of retinal fundus images under 3 different conditions. The conditions were to (1) screen the fundus image by themselves (solo); (2) screen the fundus image after exposure to the retina image classification of the ARIA system (ARIA answer); and (3) screen the fundus image after exposure to the classification of the ARIA system, as well as its level of confidence and an attention map highlighting the most important areas of interest in the image according to the ARIA system (ARIA explanation). The ophthalmologists' classification in each condition and the result from the ARIA system were compared against a gold standard generated by consulting and aggregating the opinion of 3 retina specialists for each fundus image. RESULTS: The ARIA system was able to classify referable vs nonreferable cases with an area under the receiver operating characteristic curve of 98%, a sensitivity of 95.1%, and a specificity of 91.5% for international patient cases. There was an area under the receiver operating characteristic curve of 98.3%, a sensitivity of 95.2%, and a specificity of 90% for Mexican patient cases. The ARIA system performance was more successful than the average performance of the 17 ophthalmologists enrolled in the study. Additionally, the results suggest that the ARIA system can be useful as an assistive tool, as sensitivity was significantly higher in the experimental condition where ophthalmologists were exposed to the ARIA system's answer prior to their own classification (93.3%), compared with the sensitivity of the condition where participants assessed the images independently (87.3%; P=.05). CONCLUSIONS: These results demonstrate that both independent and assistive use cases of the ARIA system present, for Latin American countries such as Mexico, a substantial opportunity toward expanding the monitoring capacity for the early detection of diabetes-related blindness.

Fundus autofluorescence in premature infants.

To describe fundus autofluorescence (FAF) patterns in premature infants and to determine whether FAF increases gradually with increasing post-gestational age. This was a cross-sectional, observational and descriptive case series. FAF images were obtained from patients screened for Retinopathy of Prematurity. The presence of the following hypo-autofluorescence areas/structures was graded and ranked: macular pigment (foveal centre), optic nerve head, peripapillary vessels/vascular arcade (PP/VA), and equatorial vessels (EqV). Ranks were attributed to the number of structures visualized from the posterior pole towards the periphery. The rank of FAF could then be analysed by Spearman's correlation against age. Additionally, patients were divided by age into group 1 (< 40 weeks of corrected gestational age (WCGA)) and group 2 (> 40 WCGA). Differences between groups were tested with the Mann-Whitney U test. Thirteen patients were analysed. The mean WCGA at examination was 47.85 weeks. Spearman's correlation showed a strong positive correlation (r = 0.714) (P = 0.006) of FAF and WCGA. The Mann-Whitney U test revealed that the PP/VA and EqV were significantly more visible at > 40 WCGA than at < 40 WCGA (8.0 [P = 0.016] and 7.5 [P = 0.03], respectively). Patterns of FAF are described for the first time in premature infants. FAF increases gradually with age and centrifugally from the posterior pole towards the equator in premature infants.

Abnormal N-Glycosylation of Human Lens Epithelial Cells in Type-2 Diabetes May Contribute to Cataract Progression.

PURPOSE: In order to better understand cataract development, we analyzed the glycosylation profile of human lens epithelial cells (HLECs) from anterior lens capsules of type 2 diabetes mellitus (T2DM) and non-diabetic (ND) patients undergoing routine cataract surgery. SETTING: Research Department of the Asociación para Evitar la Ceguera, Hospital "Dr. Luis Sánchez Bulnes", Mexico. DESIGN: Experimental study. METHODS: Evaluation of anterior lens capsules from T2DM and ND patients undergoing phacoemulsification and free from other ocular diseases. RESULTS: Hematoxylin-eosin staining revealed HLECs alterations in T2DM samples. From lectins with different sugar specificities used, concanavalin A showed significant differences, labeling homogeneously both in the cytoplasm and in cell membranes in ND capsules, while in T2DM capsules, in addition to membrane and cytoplasm labeling, there were perinuclear vesicles with high concanavalin A labeling. Two-dimensional gel electrophoresis showed that T2DM patients have a ~65-kDa spot with an isoelectric point of 5.5 with a higher density compared to ND capsules, and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis showed 62% homology with type-1 cytokeratin. Immunohistochemistry using anti-pan cytokeratin antibody revealed co-localization with concanavalin A, and a lectin blot revealed with concanavalin A showed a band of ~65 kDa, a molecular weight that corresponds to human type 1 cytokeratin. CONCLUSION: These results suggest that over-expression of N-glycosidically linked human type 1 cytokeratin may induce capsule disruption and affect selective permeability, allowing the entry of different molecules to the lens that facilitate cataract progression.

Oculocardiac Reflex During Intravitreal Injection.

Oculocardiac reflex (OCR) has been described to occur with mechanical manipulation of the eye, eyelids or orbit. There are no reports in the literature of OCR during intravitreal injection (IVI). This may be due to the fact that heart rate is not monitored during the procedure. We aimed to evaluate OCR during IVI. A total of 532 patients were enrolled in the study at Asociacion para Evitar la Ceguera en Mexico. Mexico City, Mexico. IVI was performed on one eye in every patient with diabetic retinopathy (DR), age related macular degeneration (AMD) or choroidal neovascularization (CNV) secondary to pathological myopia. Heart rate was monitored with a pulse oximeter before, during and after injection. OCR was defined as a 20% decrease or more of basal heart rate. The population enrolled included 270 females and 262 males with mean age of 63.8 years. A decrease in heart rate of 20% or more occurred in 18 patients during IVI (3.3%; 95% confidence interval 1.85% and 4.92%). OCR was asymptomatic in these patients. OCR occurred in 3.3% of our patients during IVI. Hence, OCR must be considered when performing IVI.

Interplay between Oxidative Stress, Inflammation, and Amyloidosis in the Anterior Segment of the Eye; Its Pathological Implications.

There are different pathologies associated with amyloidogenic processes caused by the increase of reactive oxygen species (ROS) and the overactivation of inflammatory responses. These alterations are present in different regions of the anterior segment of the eye, and they have been associated with the development and progression of ocular pathologies, such as glaucoma, dry eye syndrome, keratitis, and cataracts among other pathologies. Aim. To discuss briefly the anatomical characteristics of the anterior segment of the eye and describe the interaction between oxidative stress (OS) and inflammatory responses, emphasizing the misfolding of several proteins leading to amyloidogenic processes occurring in the anterior segment and their implications in the development of ocular diseases. We performed a search on PubMed, CINAHL, and Embase using the MeSH terms "eye," "anterior segment", "inflammation", "oxidative stress", and "amyloidosis". The search encompassed manuscripts published up to April 2019. A hundred forty-four published studies met the inclusion criteria. We present the current knowledge regarding the interaction between OS and the activation of inflammatory processes and how both can cause conformational changes in several peptides and proteins in each compartment of the anterior segment. However, we found that there is no consensus about which factor is the first to cause amyloidosis. Our conclusions suggest that there is an interplay among these factors forming a vicious cycle that leads to the loss of protein structure in ocular pathologies, and multifactorial therapies should be developed to avoid protein misfolding and to stop the progression of ocular pathologies.

A Teleophthalmology Support System Based on the Visibility of Retinal Elements Using the CNNs.

This paper proposes a teleophthalmology support system in which we use algorithms of object detection and semantic segmentation, such as faster region-based CNN (FR-CNN) and SegNet, based on several CNN architectures such as: Vgg16, MobileNet, AlexNet, etc. These are used to segment and analyze the principal anatomical elements, such as optic disc (OD), region of interest (ROI) composed by the macular region, real retinal region, and vessels. Unlike the conventional retinal image quality assessment system, the proposed system provides some possible reasons about the low-quality image to support the operator of an ophthalmoscope and patient to acquire and transmit a better-quality image to central eye hospital for its diagnosis. The proposed system consists of four steps: OD detection, OD quality analysis, obstruction detection of the region of interest (ROI), and vessel segmentation. For the OD detection, artefacts and vessel segmentation, the FR-CNN and SegNet are used, while for the OD quality analysis, we use transfer learning. The proposed system provides accuracies of 0.93 for the OD detection, 0.86 for OD image quality, 1.0 for artefact detection, and 0.98 for vessel segmentation. As the global performance metric, the kappa-based agreement score between ophthalmologist and the proposed system is calculated, which is higher than the score between ophthalmologist and general practitioner.

Clinical Evaluation of a Novel Electromechanical Topical Ocular Drug Delivery System: Two Phase 1 Proof of Concept Studies.

PURPOSE: Self-administration of topical ophthalmic therapies remains challenging for many patients as errors due to improper technique are common. The aim of the current studies was to evaluate a novel electromechanical topical ocular drug delivery device designed to facilitate precise dosing and accurate delivery with substantially lower drug exposure than conventional eye drops. PATIENTS AND METHODS: Two randomized Phase 1 studies were performed to evaluate the efficacy and safety of a single dose of a topical ophthalmic solution administered as a ~9 µL microfluid stream via the test device compared with a ~30-40 µL drop delivered via conventional dropper in healthy subjects (Trial 1) and glaucoma patients (Trial 2). In Trial 1, a 1% tropicamide/2.5% phenylephrine solution was administered via the test device in one eye and by conventional dropper in the contralateral eye. Pupil dilation was measured at 30 min intervals post-instillation and subject comfort was assessed using a visual analogue scale (range, 0-100). In Trial 2, patients were randomized to receive latanoprost 0.005% via the test device or conventional dropper. Intraocular pressure was measured at baseline and 4-8 hrs post-instillation. RESULTS: In Trial 1 (N=20), mean (SD) pupil diameter 30 mins post-instillation increased by 3.4 (0.9) and 3.5 (1.0) mm in the test and control eyes, respectively. The mean comfort score was 81.7 for the test device versus 57.3 for conventional dropper delivery. In Trial 2 (N=18), the mean change in intraocular pressure following administration of latanoprost was -5.0 (1.8) and -4.3 (3.3) mm Hg in the test and control groups, respectively. No serious adverse events were observed in either study. CONCLUSION: Administration of a single dose of topical ophthalmic therapy via an electromechanical drug delivery device resulted in comparable effects on pupil dilation and intraocular pressure with lower drug exposure and increased patient comfort compared with conventional dropper delivery.

A Proposed Method to Quantify Vitreous Hemorrhage by Ultrasound.

PURPOSE: To propose a method for quantification of vitreous hemorrhages (VH) termed minimum image gain (MIG). Therefore, to obtain MIG measurements in patients with VH and to compare them to normal controls; to compare results between graders; and to obtain and compare MIG from two different ultrasound systems. METHODS: Retrospective and cross-sectional, observational, and comparative study performed in two parts: Part 1) Retrospective comparison of MIG in VH vs controls by two experienced graders, with intra/inter-observer variability: MIG technique is described. MIG is performed retrospectively in two groups, VH patients and normal controls. Groups are compared with independent samples t-test. Intra- and interobserver variability between graders was obtained. Part 2) Cross-sectional analysis of variability from nonexperienced graders and with different ultrasound systems: MIG is performed in cross-sectional measurements of VH patients, by two unexperienced graders, and with two ultrasound systems. Interobserver variability and Bland-Altman plot with levels of agreement (LoA) were obtained. RESULTS: Part 1: 50 patients with VH resulted in mean MIG: 52.8 dB; 34 controls resulted in mean MIG: 77.97 dB. Independent samples t-test resulted in a statistical significant difference. Intra- and inter-observer variability resulted in an almost perfect agreement between experienced graders. Part 2: 63 patients with VH, mean MIG: 56.19 dB. Inter-observer variability resulted in a very high agreement between unexperienced observers. LoA resulted in a statistical difference between the two ultrasound systems. CONCLUSION: MIG may provide an objective and reproducible way to quantify vitreous hemorrhage density and potentially any vitreous humor opacity. Agreement is high even with unexperienced graders. However, the two ultrasound systems analyzed may not be interchangeable.

Is subretinal surgery feasible for a non-responsive juxtafoveal type 2 choroidal neovascular membrane?

PURPOSE: To describe the long-term outcome of a patient with multifocal choroiditis, who underwent surgical removal of a type 2 choroidal neovascular membrane employing 23 G pars plana vitrectomy. OBSERVATIONS: A 50-year-old man was treated with 3 monthly intravitreal bevacizumab injections, but despite treatment, visual acuity continued to worsen from 20/40 to 20/100, and bleeding was not receding. A minimal invasive pars plana vitrectomy was performed for surgical removal of the neovascular complex without any complicating incident. Subsequent visual acuity was 20/25 for more than eleven years. CONCLUSIONS AND IMPORTANCE: Surgical removal of choroidal neovascular membranes employing minimal invasive surgery in addition to anti-VEGF therapy, and OCT evaluation can be a viable approach for selected cases of juxtafoveal type 2 CNV.

Anti-VEGF treatment switch in neovascular age-related macular degeneration: a comparison of aflibercept versus ranibizumab after a single-dose switch.

PURPOSE: To determine the effect achieved from a single dose of anti-VEGF treatment switch, in patients with nAMD previously treated with bevacizumab, switched to either aflibercept or ranibizumab, and to compare the response between aflibercept and ranibizumab. METHODS: In retrospective, observational, and comparative study, patients were divided into two groups: Group 1, patients switched to aflibercept; Group 2, patients switched to ranibizumab. Paired samples t test was performed to measure differences in central macular thickness (CMT). To compare whether there were differences between groups mixed-design ANOVA was used. RESULTS: In Group 1, CMT changed from 360.51 to 260.16 µm, presenting a significant mean difference from PreSwitch to PostSwitch of 100.34 µm (p = 0.002, paired samples t test). In Group 2, CMT changed from 366.33 to 260.72 µm, showing a significant difference from PreSwitch to PostSwitch of 105.61 µm (p ≤ 0.000, paired samples t test). The mixed-design ANOVA compared both groups and resulted in a nonsignificant value of 0.90. CONCLUSION: The effect achieved from a single dose in patients switched to aflibercept or ranibizumab reduced significantly CMT measurements. Comparing aflibercept and ranibizumab, the effect appears to be similar in both drugs, in terms of reduction of CMT.

Age-Related Macular Degeneration: New Paradigms for Treatment and Management of AMD.

Age-related macular degeneration (AMD) is a well-characterized and extensively studied disease. It is currently considered the leading cause of visual disability among patients over 60 years. The hallmark of early AMD is the formation of drusen, pigmentary changes at the macula, and mild to moderate vision loss. There are two forms of AMD: the "dry" and the "wet" form that is less frequent but is responsible for 90% of acute blindness due to AMD. Risk factors have been associated with AMD progression, and they are taking relevance to understand how AMD develops: (1) advanced age and the exposition to environmental factors inducing high levels of oxidative stress damaging the macula and (2) this damage, which causes inflammation inducing a vicious cycle, altogether causing central vision loss. There is neither a cure nor treatment to prevent AMD. However, there are some treatments available for the wet form of AMD. This article will review some molecular and cellular mechanisms associated with the onset of AMD focusing on feasible treatments for each related factor in the development of this pathology such as vascular endothelial growth factor, oxidative stress, failure of the clearance of proteins and organelles, and glial cell dysfunction in AMD.

Current Anti-Integrin Therapy for Ocular Disease.

The integrin family of cell adhesion molecules mediates homeostasis, signal transduction, and various other interactions between the cell and the extracellular matrix. Integrins are type-1 transmembrane glycoproteins located on the cell surface, widely expressed in leukocytes, which play an important role in the inflammatory pathway. The purpose of this review is to summarize the current state of anti-integrin therapy and to assess ongoing clinical trials in ocular disease. We performed a search on PubMed, CINAHL, and Embase for the published literature available using the MeSH terms: "integrin therapy" and "αLß2," "α4ß1" and "α4ß7," "αvß3," "αvß5," and "αvß1" and/or "ophthalmology," and "clinical trials." We used no language restrictions. We generated searches to account for synonyms of these keywords and MESH headings as follows: (1) "integrin," "therapy," or "treatment"; (2) "clinical trials," "ophthalmology," or "ocular." In addition, the analysis included phase 2 and phase 3 clinical trials with a minimal follow-up of six months. Integrin antagonists have shown their capacity to improve signs and symptoms of patients with dry eye disease, age-related macular degeneration, diabetic macular edema, and vitreomacular traction.

Comparison of cumulative dissipated energy delivered by active-fluidic pressure control phacoemulsification system versus gravity-fluidics.

PURPOSE: To compare the cumulative dissipated energy (CDE), aspiration time and estimated aspiration fluid utilized during phacoemulsification cataract surgery using two phacoemulsification systems . METHODS: A total of 164 consecutive eyes of 164 patients undergoing cataract surgery, 82 in the active-fluidics group and 82 in the gravity-fluidics group were enrolled in this study. Cataracts graded NII to NIII using LOCS II were included. Each subject was randomly assigned to one of the two platforms with a specific configuration: the active-fluidics Centurion ® phacoemulsification system or the gravity-fluidics Infiniti ® Vision System. CDE, aspiration time (AT) and the mean estimated aspiration fluid (EAF) were registered and compared. RESULTS: A mean age of 68.3 ± 9.8 years was found (range 57-92 years), and no significant difference was evident between both groups. A positive correlation between the CDE values obtained by both platforms was verified (r = 0.271, R 2 = 0.073, P = 0.013). Similarly, a significant correlation was evidenced for the EAF (r = 0.334, R 2 = 0.112, P = 0.046) and AT values (r = 0.156, R 2 = 0.024, P = 0.161). A statistically significantly lower CDE count, aspiration time and estimated fluid were obtained using the active-fluidics configuration when compared to the gravity-fluidics configuration by 19.29, 12.10 and 9.29%, respectively (P = 0.001, P < 0.0001 and P = 0.001). CONCLUSIONS: The active-fluidics Centurion ® phacoemulsification system achieved higher surgical efficiency than the gravity-fluidics Infiniti ® IP system for NII and NIII cataracts.

Molecular Age-Related Changes in the Anterior Segment of the Eye.

PURPOSE: To examine the current knowledge about the age-related processes in the anterior segment of the eye at a biological, clinical, and molecular level. METHODS: We reviewed the available published literature that addresses the aging process of the anterior segment of the eye and its associated molecular and physiological events. We performed a search on PubMed, CINAHL, and Embase using the MeSH terms "eye," "anterior segment," and "age." We generated searches to account for synonyms of these keywords and MESH headings as follows: (1) "Eye" AND "ageing process" OR "anterior segment ageing" and (2) "Anterior segment" AND "ageing process" OR "anterior segment" AND "molecular changes" AND "age." Results. Among the principal causes of age-dependent alterations in the anterior segment of the eye, we found the mutation of the TGF-ß gene and loss of autophagy in addition to oxidative stress, which contributes to the pathogenesis of degenerative diseases. CONCLUSIONS: In this review, we summarize the current knowledge regarding some of the molecular mechanisms related to aging in the anterior segment of the eye. We also introduce and propose potential roles of autophagy, an important mechanism responsible for maintaining homeostasis and proteostasis under stress conditions in the anterior segment during aging.