Effects of topical low-dose preservative-free hydrocortisone on intraocular pressure in patients affected by ocular surface disease with and without glaucoma.

PURPOSE: This study aims to investigate the safety and efficacy of short-term treatment for ocular surface disease (OSD) with topical low-dose (1,005 mg) preservative-free hydrocortisone in one hundred patients with and without glaucoma. METHODS: This was an open label non-randomized clinical trial. Patients with OSD with and without primary open-angle glaucoma (POAG) received topical low-dose (1,005 mg) preservative-free hydrocortisone twice daily in each eye for 2 weeks. All patients underwent a complete ophthalmological examination at baseline (T0) and at 1 (T1) and 2 (T2) weeks post-treatment. At each visit, the intraocular pressure (IOP) and the ocular surface disease index (OSDI) questionnaire scores were recorded; the Schirmer test was performed only at T0 and T2. RESULTS: The OSDI score significantly decreased in both the POAG and no-POAG groups (both p < 0.0001) after hydrocortisone treatment, with no difference between the two groups (p = 0.72). There were no significant differences in IOP and Schirmer test results between T0 and T2 in both treatment groups (p = 0.68 and p = 0.83, respectively). CONCLUSIONS: Topical low-dose (1,005 mg) preservative-free hydrocortisone is safe and effective for improving OSD symptoms both in patients with and without POAG. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov under NCT04536129 on 01/09/2020 ("retrospectively registered").

Relationship between albuminuric CKD and diabetic retinopathy in a real-world setting of type 2 diabetes: Findings from No blind study.

BACKGROUND AND AIMS: Recently, the albuminocentric view of diabetic kidney disease (DKD) in type 2 diabetes (T2DM) has been changing. Therefore, the relationship between diabetic retinopathy (DR) and chronic kidney disease (CKD) has to be addressed according to this new clinical presentation of DKD. The aim of this study was to evaluate, in a real-world setting, the correlation DR-DKD in T2DM. METHODS AND RESULTS: A total of 2068 type 2 diabetic patients enrolled in a multicenter cross-sectional study were investigated. Albuminuric subjects were largely prevalent among subjects with DR (p = 0.019). In the whole study population, no difference in albumin excretion rate (AER) was observed between presence/absence of DR; instead, AER was significantly higher among patients with glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (CKD) (p = 0.009), above all in those with CKD and AER ≥0.03 g/24 h (p = 0.005). Multivariate analysis confirmed that eGFR (O.R. 0.976; 95% C.I.: 0.960-1.028; p < 0.001) and AER (O.R. 1.249; 95% C.I. 1.001-1.619; p = 0.004) were independently associated with DR and HDL-cholesterol (O.R.: 1.042; 95% C.I.: 1.011-1.120; p = 0.014). Additionally, among patients with eGFR <60 mL/min/1.73 m2 and albuminuria, both eGFR and AER significantly varied between those with/without DR (p = 0.012 and p = 0.005, respectively), and this finding was observed among only albuminuric patients. Analogous results were obtained considering DR classification. AER was significantly higher among subjects with either proliferative DR (PDR) or severe nonproliferative DR (NPDR), with regard to mild NPDR (0.498 and 0.938 g/die vs. 0.101 g/die; p < 0.001, respectively). Similar results were obtained in the specular subgroups. CONCLUSION: In T2DM with DKD, the AER seems to be related to the presence of DR. This association is confirmed above all in those with more severe DR.

Diabetic retinopathy, a vascular and inflammatory disease: Therapeutic implications.

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of visual impairment in the working-age population in the Western world. Diabetic macular oedema (DME) is one of the major complications of DR. Therapy with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs has become the gold standard treatment for DR and its complications. However, these drugs have no effect on the pathogenesis of DR and must be administered frequently via invasive intravitreal injections over many years. Thus, there is a pressing need to develop new therapeutic strategies to improve the treatment of this devastating disease. Indeed, an increasing volume of data supports the role of the inflammatory process in the pathogenesis of DR itself and its complications, including both increased retinal vascular permeability and neovascularization. Inflammation may also contribute to retinal neurodegeneration. Evidence that low-grade inflammation plays a critical role in the pathogenesis of DME has opened up new pathways and targets for the development of improved treatments. Anti-inflammatory compounds such as intravitreal glucocorticoids, topical non-steroidal anti-inflammatory drugs (NSAIDs), antioxidants, inflammatory molecule inhibitors, renin-angiotensin system (RAS) blockers and natural anti-inflammatory therapies may all be considered to reduce the rate of administration of antineovascularization agents in the treatment of DR. This report describes the current state of knowledge of the potential role of anti-inflammatory drugs in controlling the onset and evolution of DR and DME.

Epi-Off versus Epi-On Corneal Collagen Cross-Linking in Keratoconus Patients: A Comparative Study through 2-Year Follow-Up.

AIM: To evaluate two different techniques of cross-linking: standard epithelium-off (CXL epi-off) versus transepithelial (CXL epi-on) cross-linking in patient with progressive keratoconus. METHODS: Forty eyes from 32 patients with progressive keratoconus were prospectively enrolled from June 2014 to June 2015 in this nonblinded, randomized comparative study. Twenty eyes were treated by CXL epi-off and 20 by CLX epi-on, randomly assigned, and followed for 2 years. All patients underwent a complete ophthalmologic testing that included uncorrected and best corrected visual acuity, central and peripheral corneal thickness, corneal astigmatism, simulated maximum, minimum, and average keratometry, corneal confocal microscopy, Schirmer I and break-up time (BUT) tests, and the Ocular Surface Disease Index. Intra- and postoperative complications were recorded. The solution used for CXL epi-off comprised riboflavin 0.1% and dextran 20.0% (Ricrolin), whereas the solution for CXL epi-on (Ricrolin TE) comprised riboflavin 0.1%, dextran 15.0%, trometamol (Tris), and ethylenediaminetetraacetic acid. Ultraviolet-A treatment was performed with a UV-X system at 3 mW/cm2. RESULTS: In both groups, a significant improvement in visual function (Group 1: baseline 0.36 ± 0.16 logMAR, two-year follow-up 0.22 ± 0.17 logMAR, p=0.01; Group 2: baseline 0.32 ± 0.18 logMAR, 2-year follow-up 0.27 ± 0.19 logMAR, p=0.01) was recorded. Keratometry remained unchanged in both groups. The mean corneal thickness showed a significant reduction (mean difference of corneal thickness: -55 micron and -71 micron, resp.). One-month after treatment, OSDI© reached 13.56 ± 2.15 in Group 1 (p=0.03) and 11.26 ± 2.12 in Group 2 (p=0.04). At confocal microscopy, abnormal corneal nerve alterations were found in both groups. Fibrotic reaction (43.75%) and activated keratocyte (62.6%) were more commonly recorded in Group 1 than in Group 2 (25.0% and 18.75%), with p=0.668 and 0.356, respectively. CONCLUSION: Our findings demonstrate that both procedures are able to slow keratoconus progression. Both treatment modalities are equivalent in terms of results and related complications. CXL epi-on technique is preferable to CXL epi-off since it preserves the corneal thickness and improves visual acuity, also reducing the postoperative ocular discomfort during the study period.

Effects of an antioxidant protective topical formulation on eye exposed to ultraviolet-irradiation: a study in rabbit animal model.

Ultraviolet-radiation exerts a well-known role in the development of various ocular diseases and may contribute to the progress of age-related macular degeneration. Therefore, the use of compounds able to protect the eyes from UV-induced cellular damage is challenging. The aim of this study has been to test the protective effects of an antioxidant topical formulation against UV-induced damage in rabbit eyes. Twelve male rabbits were used. Animals were divided into 4 groups of 3 animals each. Control group (CG) did not receive any irradiation and/or eye drop. The other three experimental groups were treated as follows: the first group received only UVR irradiation for 30 min, without eye drop supplementation (Irradiation group, IG), the second (G30) and the third (G60) groups received UV irradiation for 30' and 60', respectively, and eye drop supplementation (riboflavin, d-alpha-tocopheryl polyethylene glycol, proline, glycine, lysine and leucine solution) every 15 min for three hours. In the IG group a significant increase of oxidized glutathione (GSSG) and hydrogen peroxide (H(2)O(2)) was recorded in the aqueous humor, whereas ascorbic acid levels were significantly lower when compared to control eyes. In the groups exposed to UVR rays for 30 min, and treated with the topical antioxidant formulation, the GSSG, H(2)O(2) and ascorbic acid levels were similar to those recorded in controls, whereas in the G60 group the three markers significantly differ from control group. In the lens, a significant decrease of alpha tocopherol and total antioxidant capacity (TAC) was recorded in IG-animals as compared to control group, whereas malondialdehyde (MDA) levels were significantly higher in UV-induced eye than in control eyes. In the G30 groups the alpha tocopherol, MDA and TAC levels do not significantly differ from those recorded in controls, whereas in the G60 group these three markers significantly differ from control group. Present findings demonstrate that topical treatment with the antioxidant formulation used herein protects ocular structures from oxidative stress induced by UV exposure in in vivo animal model.

ILM peeling in nontractional diabetic macular edema: review and metanalysis.

PURPOSE: To evaluate the effect of internal limiting membrane (ILM) peeling during vitrectomy for nontractional diabetic macular edema. METHODS: PUBMED, MEDLINE and CENTRAL were reviewed using the following terms (or combination of terms): diabetic macular edema, nontractional diabetic macular edema, internal limiting membrane peeling, vitrectomy, Müller cells. Randomized and nonrandomized studies were included. The eligible studies compared anatomical and functional outcomes of vitrectomy with or without ILM peeling for tractional and nontractional diabetic macular edema. Postoperative best-corrected visual acuity and central macular thickness were considered, respectively, the primary and secondary outcomes. Meta-analysis on mean differences between vitrectomy with and without ILM peeling was performed using inverse variance method in random effects. RESULTS: Four studies with 672 patients were eligible for analysis. No significant difference was found between postoperative best-corrected visual acuity or best-corrected visual acuity change of ILM peeling group compared with nonpeeling group. There was no significant difference in postoperative central macular thickness and central macular thickness reduction between the two groups. CONCLUSIONS: The visual acuity outcomes in patients affected by nontractional diabetic macular edema using pars plana vitrectomy with ILM peeling versus no ILM peeling were not significantly different. A larger prospective and randomized study would be necessary.

The effect of Laurus nobilis on the blood and lenses antioxidant activity in rabbit under fat-enriched diet.

Fat-enriched diet is strongly associated with cataract development. Laurus nobilis shows antioxidant activity. Herein we evaluated the effect of Laurus nobilis oral administration on the blood and lenses antioxidant activity in rabbits under fat-enriched diet. Sixty rabbits divided into 4 groups were used. One group represented the control (N-CTR). The second group (P-CTR) fed a diet supplemented with 2.5 % of pig fat; the third group (EXP1) received a diet supplemented with 2.5 % of pig fat and 1 g/kg of dried-bay leaves; the fourth group (EXP2) was treated with dried-bay leaves at the rate of 1 g/kg of feed. At baseline and at the end of the study (56 days) the following blood parameters were determined: thiobarbituric acid reactive substances (TBARS), reactive oxygen metabolites (ROMs), total phenols, superoxide dismutase (SOD), oxygen radical absorbance capacity (ORAC(pca)), ferric ion reducing antioxidant power (FRAP), retinol and alfa-tocopherol. At the end of the follow-up, the eyes were enucleated and the antioxidant profile, such as total antioxidant activity (TAC), TBARS, retinol and alfa-tocopherol of lenses was evaluated. Plasma ROMs and TBARS levels were statistically lower in the groups receiving bay leaves integration. A significant increase of plasma retinol, FRAP and ORAC(pca) levels was found in EXP1 and EXP2 groups, whereas plasma alfa-tocopherol resulted statistically higher only in EXP2 group. Bay leaves supplementation enhanced TAC, retinol and alfa-tocopherol in rabbit lens, particularly in EXP2 group; whereas lenses TBARS levels significantly decreased in both treated groups. These findings demonstrate that Laurus nobilis oral administration exerts a protective effect on the risk of cataract development in rabbits under fat-enriched diet.

Reduced-fluence verteporfin photodynamic therapy plus ranibizumab for choroidal neovascularization in pathologic myopia.

BACKGROUND: To demonstrate the efficacy of intravitreal ranibizumab (IVR) in combination with reduced-fluence photodynamic therapy (RF-PDT) in patients with choroidal neovascularization (CNV) secondary to pathologic myopia. METHODS: Sixty patients affected by myopic CNV (mCNV) were randomized to receive either ranibizumab 0.5 mg monotherapy (RM; n = 20), standard fluence PDT (SF-PDT, n = 20) or RF-PDT combination therapy (n = 20). Subsequently, IVR was injected as needed. All patients were evaluated for 48 weeks. RESULTS: Mean BCVA change at 48 weeks was + 0.2 and +15 letters with SF or RFPDT plus ranibizumab, respectively, compared with +16.8 letters with RM. At 48 weeks, mean central foveal thickness (CFT) decrease from baseline was 58 ± 15 µm, 91.4 ± 43.8 µm, and 85 ± 41.5 µm for the verteporfin SF, RF and RM groups, respectively. Macular sensitivity improvement was + 0.4 db, + 1.9 dB and + 2.7 dB for the verteporfin SF, RF and RM groups, respectively. CONCLUSIONS: Ranibizumab monotherapy or combined with RF-PDT improved BCVA and macular sensitivity in patients affected by mCNV, whereas CFT results were reduced. SF-PDT combination regimen mostly stabilized vision at 48 weeks. Among all groups, the RF-PDT seemed to reduce the number of ranibizumab retreatments.

Dietary effect of dried bay leaves (Laurus nobilis) meal on some biochemical parameters and on plasma oxidative status in New Zealand white growing rabbit.

Effects of dietary supplementation of Laurus nobilis on selected biochemical parameters and plasma oxidative status in growing rabbits, fed with and without enriched-fat diet, integrated with and without dried bay leaves meal, were investigated. In the test, 120 New Zealand white 35-day-old male rabbits were divided into four homogeneous groups of 30 animals each. A negative control group (CON) received a feed that met the animal nutrient requirement; a positive control group (CG) receiving a supplement of 2.5% pig fat in feed; an experimental group (GA) feeding an integration of 2.5% pig fat and 1 g/kg of dried bay leaves (Laurus nobilis) in feed; an experimental group (CA) with dried bay leaves at the rate of 1 g/kg in feed. The dietary integration with dried bay leaves meal have resulted in a significant decrease in the blood lipid profile, glycemic profile and liver enzymes, with reduced levels of ALT and AST, glucose, total cholesterol, LDL cholesterol, triglycerides and increased HDL cholesterol. Plasma oxidative status markers have statistically improved with an increase in blood total phenols, SOD, ORAC, the FRAP and lipo-vitamin concentration, together with a significant reduction in ROMs and the MDA values. The results of present research underline that the dietary treatment with bay leaves meal, in the extend of 1 g/kg feed, confirms the lowering cholesterol activity and the epato-protective and ipo-glycemic effect in enrich-fat diet, controlling the oxidative status of plasma markers.

In Vivo Near-Infrared Fluorescence Imaging of Aqueous Humor Outflow Structures.

The aim of this study has been to visualize the aqueous outflow system in patients affected by primary open angle glaucoma. A solution of indocyanine green (ICG) plus high viscosity viscoelastic solution was injected into the Schlemm canal during surgery in 10 glaucomatous patients undergoing canaloplasty. Soon after injection of the dye the borders of the scleral flap were completely stained due to partial reflux caused by the intrachannel resistance; progression of the dye along the Schlemm canal starting from the site of injection was then visualized. The filling of the collector channels was observed only in the patent portions of the Schlemm canal. The only noticeable aqueous veins were located in correspondence of the quadrant in which both the Schlemm canal and the collectors were patent. Lastly, a retrograde filling, of glomerular-shaped structures, deepest to the Schlemm canal was observed in the quadrants where the pathway was functioning. Our findings show that injection of a mixture composed of ICG and viscoelastic solution into the Schlemm canal allows a clear visualization of the functioning portions of the conventional outflow pathway. In addition, a retrograde filling of structures presumably located into the iris was also recorded. Clinical Trial Registration. Our study is registered in ISRCTN registry, number 54005880, DOI 10.1186/ISRCTN54005880.

Diabetic Retinopathy: Vascular and Inflammatory Disease.

Diabetic retinopathy (DR) is the leading cause of visual impairment in the working-age population of the Western world. The pathogenesis of DR is complex and several vascular, inflammatory, and neuronal mechanisms are involved. Inflammation mediates structural and molecular alterations associated with DR. However, the molecular mechanisms underlying the inflammatory pathways associated with DR are not completely characterized. Previous studies indicate that tissue hypoxia and dysregulation of immune responses associated with diabetes mellitus can induce increased expression of numerous vitreous mediators responsible for DR development. Thus, analysis of vitreous humor obtained from diabetic patients has made it possible to identify some of the mediators (cytokines, chemokines, and other factors) responsible for DR pathogenesis. Further studies are needed to better understand the relationship between inflammation and DR. Herein the main vitreous-related factors triggering the occurrence of retinal complication in diabetes are highlighted.

Effect of intravitreal bevacizumab on serum, aqueous, and vitreous humor levels of erythropoietin in patients with proliferative diabetic retinopathy.

AIM: The aim of this study was to evaluate concentrations of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in serum, aqueous and vitreous humour of diabetic patients with proliferative retinopathy (PDR) and to verify their possible modifications induced by intravitreal injection of bevacizumab (IVB). METHODS: This prospective observational study was performed on patients who underwent vitrectomy for proliferative diabetic retinopathy and macular hole or pucker. The study sample consisted of 33 patients with proliferative diabetic retinopathy and 20 non-diabetic patients with macular hole or pucker. EPO and VEGF levels in serum, aqueous and vitreous humour were measured in both groups. In diabetic patients measures were performed before and after IVB. RESULTS: EPO and VEGF levels in aqueous and vitreous humour were markedly increased in diabetic patients with PDR as compared with those recorded in the control group (P<0.001); contrarily, EPO serum levels were similar in both groups (p=not significant). IVB did not affect EPO levels (aqueous 39.1 ± 29.2 vs. 38.6 ± 26.1; vitreous 179.3 ± 88.3 vs. 131.6 ± 67.8; serum 9.2 ± 5.8 vs. 6.9 ± 3.7 mUI/mL); conversely, VEGF concentration significantly decreased 15 days after IVB in serum and ocular fluids (aqueous 141.6 ± 12.3 vs. 81.4 ± 5.4; vitreous 180.4 ± 45.8 vs. 95.8 ± 23.6; serum 113.9 ± 52.8 vs. 73.2 ± 65.6 mUI/mL). CONCLUSION: These findings demonstrate that the production of VEGF and EPO is regulated by different mechanisms. Intraocular levels of EPO in diabetic patients were significantly higher than those recorded in serum, suggesting a local production. In addition, bevacizumab does not influence intraocular levels of EPO.

The p85 regulatory subunit of PI3K mediates cAMP-PKA and insulin biological effects on MCF-7 cell growth and motility.

Recent studies have shown that hyperinsulinemia may increase the cancer risk. Moreover, many tumors demonstrate an increased activation of IR signaling pathways. Phosphatidylinositol 3-kinase (PI3K) is necessary for insulin action. In epithelial cells, which do not express GLUT4 and gluconeogenic enzymes, insulin-mediated PI3K activation regulates cell survival, growth, and motility. Although the involvement of the regulatory subunit of PI3K (p85α (PI3K)) in insulin signal transduction has been extensively studied, the function of its N-terminus remains elusive. It has been identified as a serine (S83) in the p85α (PI3K) that is phosphorylated by protein kinase A (PKA). To determine the molecular mechanism linking PKA to insulin-mediated PI3K activation, we used p85α (PI3K) mutated forms to prevent phosphorylation (p85A) or to mimic the phosphorylated residue (p85D). We demonstrated that phosphorylation of p85α (PI3K)S83 modulates the formation of the p85α (PI3K)/IRS-1 complex and its subcellular localization influencing the kinetics of the insulin signaling both on MAPK-ERK and AKT pathways. Furthermore, the p85α (PI3K)S83 phosphorylation plays a central role in the control of insulin-mediated cell proliferation, cell migration, and adhesion. This study highlights the p85α (PI3K)S83 role as a key regulator of cell proliferation and motility induced by insulin in MCF-7 cells breast cancer model.

Serum and intraocular concentrations of erythropoietin and vascular endothelial growth factor in patients with type 2 diabetes and proliferative retinopathy.

AIM: This study compared systemic and intraocular concentrations of erythropoietin (EPO) and vascular endothelial growth factor (VEGF) in patients with type 2 diabetes (T2D) and proliferative diabetic retinopathy (PDR) with levels in patients without diabetes, and looked for possible correlations between the concentrations found and other variables analyzed. METHODS: Concentrations of EPO and VEGF were measured in the aqueous and vitreous humours and serum of patients undergoing vitrectomy for PDR (33 patients) or for macular holes or puckers (20 control patients). EPO was assayed by radioimmunoassay, with a lower limit of detection (LOD) of 1.0 mIU/mL. VEGF was assayed using enzyme-linked immunosorbent assay (ELISA), with a lower LOD of 10.0 pg/mL. RESULTS: EPO concentrations in serum did not differ significantly between the two groups, whereas EPO in vitreous and aqueous were higher in diabetic than in non-diabetic patients. VEGF in serum was lower in diabetic patients than in non-diabetics; conversely, VEGF concentrations in vitreous were significantly higher in diabetic patients. A direct correlation was found between vitreous and aqueous EPO concentrations, and between vitreous EPO and blood glucose concentrations. A significant, negative correlation between vitreous EPO concentration and age was also recorded. CONCLUSION: High EPO concentrations in the vitreous of patients with PDR and its correlation with blood glucose suggest that EPO could play a role in the pathogenesis of PDR. All possible factors affecting serum and ocular concentrations of EPO and VEGF should be determined to identify compounds able to prevent and control this serious microvascular complication of diabetes.

Lattice Corneal Dystrophy: a report of two cases in twin sisters due to 3 mutations (T1620C, C1416T, A1924G) in the TGFBI (BIGH3) gene.

Phenotypic characteristics associated with mutations in the transforming growth factor beta-induced (TGFBI) gene in two twin sisters suffering from lattice corneal dystrophy are reported. Genomic DNA was extracted from peripheral blood and 3 new mutations in association with exons 11-12-14 of the TGFBI gene were found.

Neurotrophic keratitis.

Neurotrophic keratitis (NK) is a rare degenerative corneal disease that occurs as a result of partial or total impairment of trigeminal innervations, leading to a reduction (hypoesthesia) in or loss (anaesthesia) of corneal sensitivity. The impairment of sensory innervation causes a reduction in the lacrimation reflex and the vitality, metabolism and mitosis of epithelial cells, with subsequent deficiency in epithelial repair, stromal and intracellular oedema, loss of microvilli, and abnormal development of the basal lamina. Several recent studies have proposed different therapies based on different aetiopathogenetic theories. The aim of the therapy is to treat aetiopathogenesis and, at the same time, promote corneal healing. In this paper, we report the aetiology, diagnosis, management, and medical and surgical treatment of NK, also indicating future treatments based on the most recent studies.

TNF-alpha levels in tears: a novel biomarker to assess the degree of diabetic retinopathy.

We assess the level of tumour necrosis factor alpha (TNF-alpha) in tear fluids and other serum parameters associated with diabetes in different degrees of diabetic retinopathy. We have performed a prospective, nonrandomized, observational study. Study population consisted of 16 healthy subjects (controls) and 32 type 2 diabetic patients: 16 affected by proliferative diabetic retinopathy (PDR) and 16 with nonproliferative retinopathy (NDPR, background/preproliferative). Body mass index, urinary albumin, blood glucose, HbA1c, and tear levels of TNF-alpha were measured in all subjects. The value of glycaemia, microalbuminurea, and Body mass index in diabetic retinopathy groups were higher than those in control group (P < 0.05). Glycemia in NPDR: 6.6 mmol/L (range: 5.8-6.3); in PDR: 6.7 mmol/L (range: 6.1-7.2); in control: 5.7 mmol/L (range: 4.9-6.1); microalbuminurea in NPDR: 10.6 mg/L (range: 5.6-20); in PDR: 25.2 mg/L (range: 17-40); in control: 5.3 mg/L (range: 2.6-10); Body mass index in NPDR: 26 Kg/m(2) (range: 20.3-40); in PDR: 28 Kg/m(2) (range 20.3-52); in control: 21 Kg/m(2) (range 19-26). The TNF-alpha concentrations in tears increase with the severity of pathology and were lower in control group than in diabetic subjects. In the end, the level of TNF-alpha is highly correlated with severity of diabetic retinopathy and with nephropathy. Tear fluid collection may be a useful noninvasive method for the detection of proliferative diabetic retinopathy.

Intravitreal infliximab for choroidal neovascularization in patients refractory to conventional treatments.

The aim of the study is to evaluate the effectiveness and safety of intravitreal infliximab in the course of compassionate use in patients affected by choroidal neovascularization. This prospective interventional case series includes four eligible patients, affected by exudative age-related macular degeneration (2/4), retinal angiomatous proliferation (1/4) and central retinal vein occlusion (1/4), who were refractory to conventional treatments. The patients received a single intravitreal injection of 0.05 ml of reconstituted infliximab solution (20mg/ml). The main outcomes measure were changes in best-corrected visual acuity and central retinal thickness. Patients were evaluated at baseline, every week for the first month, then every two weeks, and on demand. Morphologic parameters improved after a single infliximab intravitreal injection. However, all patients developed acute uveitis in a period ranging from 4 to 7 weeks after treatment. Control of the intraocular inflammation was achieved with topical and systemic steroids in 3 patients, whereas in one case pars plana vitrectomy was needed. A single intravitreal injection of infliximab does not seem to improve the natural history of CNV from different aetiologies. However, all patients in our series developed a serious inflammatory response that required surgical management in one case. The intravitreal administration of infliximab is hence not safe and not recommended in clinical practice.

Aflibercept in wet AMD: specific role and optimal use.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a naturally occurring glycoprotein in the body that acts as a growth factor for endothelial cells. It regulates angiogenesis, enhances vascular permeability, and plays a major role in wet age-related macular degeneration. The consistent association between choroidal neovascularization and increased VEGF expression provides a strong reason for exploring the therapeutic potential of anti-VEGF agents in the treatment of this disorder. Blockade of VEGF activity is currently the most effective strategy for arresting choroidal angiogenesis and reducing vascular permeability, which is frequently the main cause of visual acuity deterioration. In recent years, a number of other molecules have been developed to increase the efficacy and to prolong the durability of the anti-VEGF effect. Aflibercept (EYLEA®; Regeneron Pharmaceutical Inc and Bayer), also named VEGF Trap-eye, is the most recent member of the anti-VEGF armamentarium that was approved by the US Food and Drug Administration in November 2011. Because of its high binding affinity and long duration of action, this drug is considered to be a promising clinically proven anti-VEGF agent for the treatment of wet maculopathy. OBJECTIVE: This article reviews the current literature and clinical trial data regarding the efficacy and the pharmacological properties of VEGF-Trap eye and describes the possible advantages of its use over the currently used "older" anti-VEGF drugs. METHODS: For this review, a search of PubMed from January 1989 to May 2013 was performed using the following terms (or combination of terms): vascular endothelial growth factors, VEGF, age-related macular degeneration, VEGF-Trap eye in wet AMD, VEGF-Trap eye in diabetic retinopathy, VEGF-Trap eye in retinal vein occlusions, aflibercept. Studies were limited to those published in English. RESULTS AND CONCLUSION: Two Phase III clinical trials, VEGF Trap-eye Investigation of Efficacy and Safety in Wet AMD (VIEW) 1 and 2, comparing VEGF Trap-eye to ranibizumab demonstrated the noninferiority of this novel compound. The clinical equivalence of this compound against ranibizumab is maintained even when the injections are administered at 8-week intervals, which indicates the potential to reduce the risk of monthly intravitreal injections and the burden of monthly monitoring.

Work- and non-work-related eye injuries in a highly industrialized area in northern Italy: comparison between two three-year periods (1994-1996 and 2005-2007).

BACKGROUND: Ocular trauma is a major cause of monocular blindness and visual impairment in industrialized countries. OBJECTIVES: The aim of this paper was to study epidemiology, causes, and clinical features of work-related and non-work-related eye injuries in a highly industrialized area of northern Italy. METHODS: All patients hospitalized for eye injuries were enrolled. Two 3-year periods were studied (1994-1996 and 2005-2007). The variables analyzed included sex, age, social class of the patients, nature of the injuring agent (e.g., metal, plastic, etc.), place where the accident occurred (e.g., home, work, etc.), and time of the year (e.g., summer, winter, etc.). RESULTS: We enrolled 1001 men and 129 women. There were no significant differences between the two 3-year periods as regards distribution of sex, age, and location. Road-related injuries significantly decreased (p < 0.004). Comparison of injuring agents showed a decrease in metallic agents (p < 0.001) and an increase in lime agents (p < 0.001). Analysis of the type of trauma showed a decrease in blunt traumas (p < 0.001) and an increase in chemical injuries (p < 0.001) and actinic keratitis (p = 0.002). In the second 3-year period, we found a significant increase in injuries in non-Italian subjects (p < 0.001). CONCLUSIONS: Work-related injuries were the major cause of eye trauma. Road accident-related eye injuries dropped significantly in the second 3-year period. The adoption of higher safety standards, as well as information and educational campaigns, can significantly reduce work-related and non-work-related eye injuries.