Combined Phacoemulsification and Intravitreal Dexamethasone Implant (Ozurdex®) in Diabetic Patients with Coexisting Cataract and Diabetic Macular Edema.

PURPOSE: To investigate the effectiveness and safety of combined phacoemulsification and dexamethasone intravitreal implant in patients with cataract and diabetic macular edema. METHODS: In this two-center, retrospective, single-group study, the charts of 16 consecutive patients who underwent combined phacoemulsification and intravitreal dexamethasone implant were retrospectively reviewed. These 16 patients, 7 men and 9 women, were observed at least 3 months of follow-up. Primary outcome was the change of the central retinal thickness (CRT); secondary outcome was the change of best-corrected visual acuity (BCVA). Any ocular complications were recorded. RESULTS: Mean CRT decreased significantly from 486 ± 152.4 µm at baseline to 365.5 ± 91 µm at 30 days (p = .005), to 326 ± 80 µm at 60 days (p = .0004), and to 362 ± 134 µm at 90 days (p = .001). Mean BCVA was 20/105 (logMAR, 0.72 ± 0.34) at baseline and improved significantly (p ≤ .007) at all postsurgery time points. One case of ocular hypertension was observed and successfully managed with topical therapy. No endophthalmitis or other ocular complications were observed. CONCLUSION: Intravitreal slow-release dexamethasone implant combined with cataract surgery may be an effective approach on morphologic and functional outcomes for patients with cataract and diabetic macular edema for at least three months after surgery.

Plasmapheresis, Intravenous Immunoglobulins, and Autologous Serum Eyedrops in the Acute Eye Complications of Toxic Epidermal Necrolysis.

PURPOSE: Toxic epidermal necrolysis (TEN) is a rare, life-threatening, drug-induced, mucocutaneous disease, which can severely affect the ocular surface. The purpose of this study was to investigate the efficacy of plasmapheresis, human IV immunoglobulins (IVIg), and autologous serum (AS) eyedrops in the treatment of the severe acute ocular complications of TEN. METHODS: A retrospective chart review of all patients admitted to the Burn Unit, Azienda Ospedaliero-Universitaria-Sassari, Sassari, Italy, from 2009 to 2015, identified 9 patients (2 men, 7 women; mean age 63.8 ± 24.7 years) with TEN. Bilateral, acute ocular surface complications were observed in 7 (78%) patients; 3 showed catarrhal conjunctivitis, whereas 4 had severe pseudomembranous conjunctivitis and corneal ulcers. RESULTS: All patients with TEN were immediately treated with plasmapheresis and human IVIg, which produced a marked improvement in the patients' general condition. In the 3 with catarrhal conjunctivitis, preservative-free artificial tears and topical antibiotics were beneficial. In the 4 with severe pseudomembranous conjunctivitis and corneal ulcers, treatment with AS eyedrops resulted in corneal and conjunctival epithelium healing over 3-6 weeks. After a minimum follow-up of at least 12 months, there were minimal/mild residual signs and symptoms of dry eye. CONCLUSIONS: Plasmapheresis and IVIg may be life-saving and contribute to reduce ocular surface inflammation in TEN. Autologous serum eyedrops, prepared after plasmapheresis completion and IVIg infusion, may be helpful in the management of the severe acute ocular complications of TEN.

Bromfenac eyedrops in the treatment of diabetic macular edema: a pilot study.

PURPOSE: To evaluate the efficacy and safety of topical bromfenac in patients with newly diagnosed diabetic macular edema (DME). METHODS: In this pilot study including 17 patients with monocular, newly diagnosed DME, diagnosis of DME was established by the detection of retinal thickening at or within 500 µm of the center of the macula on ophthalmoscopic examination, according to the Early Treatment Diabetic Retinopathy Study classification. Central macular thickness (CMT) was determined by optical coherence tomography. Bromfenac sodium hydrate 0.9 mg/mL eyedrops were administered in the affected eye twice daily for 30 days. Primary endpoints were changes in best-corrected visual acuity (BCVA) and CMT at the end of therapy. RESULTS: Topical bromfenac significantly reduced mean CMT, from 465.41 ± 118.47 µm at baseline to 388.88 ± 152.63 µm posttreatment (p = 0.02). There was no significant change in BCVA and differences in mean macular volume fell just short of statistical significance (p = 0.06). Treatment was well-tolerated, and there were no topical or systemic side effects. CONCLUSIONS: Topical bromfenac twice daily may play a role in the reduction of DME. These preliminary results warrant further larger multicenter studies to confirm our findings and establish whether topical bromfenac may be of long-term benefit in the treatment of DME.

Plasma Homocysteine and Asymmetrical Dimethyl-l-Arginine (ADMA) and Whole Blood DNA Methylation in Early and Neovascular Age-Related Macular Degeneration: A Pilot Study.

PURPOSE/AIM: To compare the plasma levels of homocysteine and asymmetrical dimethyl-l-arginine (ADMA) and the degree of whole blood DNA methylation in patients with early and neovascular age-related macular degeneration (AMD) and in controls without maculopathy of any sort. MATERIALS AND METHODS: This observational case-control pilot study included 39 early AMD patients, 27 neovascular AMD patients and 132 sex- and age-matched controls without maculopathy. Plasma homocysteine and ADMA concentrations and the degree of whole blood DNA methylation were measured. Quantitative variables were compared by Student's t-test or Mann-Whitney test. Logistic regression models were used to investigate the significance of the association between early or wet AMD and some variables. RESULTS: There were no significant differences in mean plasma homocysteine and ADMA concentrations and in the degree of whole blood DNA methylation between patients with early or neovascular AMD and their controls. Similarly, logistic regression analysis disclosed that plasma homocysteine and ADMA levels were not associated with an increased risk for early or neovascular AMD. CONCLUSIONS: We failed to demonstrate an association between early or neovascular AMD and increased plasma homocysteine and/or ADMA. Results also suggest that the degree of whole blood DNA methylation is not a marker of AMD.

A protocol for microbiologically safe preparation, storage, and use of autologous serum eye-drops in low-income countries.

INTRODUCTION: The study aimed to investigate whether the preparation, storage, and use of autologous serum in insulin syringes is microbiologically safe. METHODOLOGY: Blood samples (10 mL) were obtained from 10 volunteers. After centrifugation, the supernatant serum was removed and distributed in 5 sterile insulin syringes for each sample; syringes were numbered 0 to 4 and labelled with the subject's details. Syringes were immediately transported to the microbiology laboratory and stored in a refrigerator at +4°C. The "0" labelled syringes were separated from the others and 100 µl of serum from each syringe was immediately seeded on chocolate and Sabouraud agar plates, which were incubated aerobically at 37°C for 96 hours to detect any bacterial and/or fungal contamination. In the next 4 days, the same procedure was repeated for the remaining syringes: on day 1, the "1" labelled syringes were analyzed; on day 2, the "2" labelled ones, and so on. In a second experiment, blood samples were obtained from 5 different volunteers. The same procedure as above was followed, but each syringe was used for repeated cultures at 2-hour intervals, for a total of 12 cultures/day. The needle was removed and replaced for each inoculation and the syringes were stored in the refrigerator after use. RESULTS: Under these experimental conditions, none of the cultures showed microbial growth. CONCLUSIONS: Results suggest that, under the protocol described, preparation, storage and use of undiluted autologous serum in insulin syringes is inexpensive, fast, and microbiologically safe. This is of great importance for low-income countries.

Detection of serum antibodies cross-reacting with Mycobacterium avium subspecies paratuberculosis and beta-cell antigen zinc transporter 8 homologous peptides in patients with high-risk proliferative diabetic retinopathy.

PURPOSE: MAP3865c, a Mycobacterium avium subspecies paratuberculosis (MAP) cell membrane protein, has a relevant sequence homology with zinc transporter 8 (ZnT8), a beta-cell membrane protein involved in Zn++ transportation. Recently, antibodies recognizing MAP3865c epitopes have been shown to cross-react with ZnT8 in type 1 diabetes patients. The purpose of this study was to detect antibodies against MAP3865c peptides in patients with high-risk proliferative diabetic retinopathy and speculate on whether they may somehow be involved in the pathogenesis of this severe retinal disorder. METHODS: Blood samples were obtained from 62 type 1 and 80 type 2 diabetes patients with high-risk proliferative diabetic retinopathy and 81 healthy controls. Antibodies against 6 highly immunogenic MAP3865c peptides were detected by indirect ELISA. RESULTS: Type 1 diabetes patients had significantly higher rates of positive antibodies than controls. Conversely, no statistically significant differences were found between type 2 diabetes patients and controls. After categorization of type 1 diabetes patients into two groups, one with positive, the other with negative antibodies, we found that they had similar mean visual acuity (∼ 0.6) and identical rates of vitreous hemorrhage (28.6%). Conversely, Hashimoto's thyroiditis prevalence was 4/13 (30.7%) in the positive antibody group and 1/49 (2%) in the negative antibody group, a statistically significant difference (P = 0.016). CONCLUSIONS: This study confirmed that type 1 diabetes patients have significantly higher rates of positive antibodies against MAP/ZnT8 peptides, but failed to find a correlation between the presence of these antibodies and the severity degree of high-risk proliferative diabetic retinopathy. The significantly higher prevalence of Hashimoto's disease among type 1 diabetes patients with positive antibodies might suggest a possible common environmental trigger for these conditions.

A biomonitoring study on blood levels of beta-hexachlorocyclohexane among people living close to an industrial area.

BACKGROUND: A chemical plant manufacturing pesticides has been operating since the 1950's in the Sacco River Valley (Central Italy). In 2005, high beta-hexachlorocyclohexane (Beta-HCH) concentrations were found in milk of cows raised and fed near the river. We report the results of a biomonitoring study conducted in this region to evaluate the body burden of Beta-HCH and to identify the determinants of the human contamination. METHODS: We defined four residential areas by their distance from the chemical plant and the river, and selected a stratified random sample of 626 people aged 25-64 years. We evaluated the association, in terms of the geometric mean ratio (GMR), between several potential determinants and Beta-HCH serum concentrations using multivariate linear regression analysis. RESULTS: Two hundred forty-six serum samples were analysed to assess Beta-HCH levels (mean concentration: 99 ng/g lipid; Standard Deviation: 121; Geometric Mean: 60.6; Geometric Standard Deviation: 2.65). We found a strong association between Beta-HCH and living in the area close to the river (GMR: 2.00; 95%CI: 1.36-2.94). Beta-HCH levels were also associated with age, level of education, use of private wells and consumption of local food. CONCLUSIONS: The results suggest that people living close to the river may have been contaminated by Beta-HCH, most likely through water from private wells and privately grown food. A programme of epidemiological and clinical surveillance is on-going on this population.

Meibomian gland dysfunction and hypercholesterolemia.

OBJECTIVE: Hypercholesterolemia (total cholesterol ≥ 200 mg/dl) is a significant risk factor for ischemic heart, cerebrovascular, and peripheral vascular disease. Increased cholesterol in the glandular secretion has been postulated to be necessary for the development of meibomian gland dysfunction (MGD), a common form of chronic blepharitis. The purpose of this study was to investigate a possible correlation between MGD and hypercholesterolemia in young and middle-aged patients (aged 18-54 years). DESIGN: Observational, case-control pilot study. PARTICIPANTS AND CONTROLS: Sixty symptomatic patients with MGD with no history of hypercholesterolemia and 63 controls without MGD and with no history of hypercholesterolemia, accrued from January 2011 to June 2012. INTERVENTIONS: Body mass index (BMI), fasting blood triglycerides, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), glucose, and creatinine were measured. Z test or Student t test was used, when appropriate, to calculate differences between groups. Stepwise logistic regression models were used to calculate the estimates of odds ratios (ORs), considering MGD as the dependent variable and including sex, age, BMI, triglycerides, total cholesterol, LDL, HDL, glucose, and creatinine as covariates. MAIN OUTCOME MEASURES: Fasting blood levels of total cholesterol, LDL, and HDL (milligrams/deciliter). RESULTS: Hypercholesterolemia was found in 35 cases (58.3%) and 4 controls (6.3%), a statistically significant difference (P < 0.0001). Mean total cholesterol, LDL, and HDL were 210.8 ± 4.4, 127.6 ± 3.9, and 61.6 ± 1.8 mg/dl, respectively, in cases and 162.9 ± 3.1, 94.2 ± 2.6, and 52.5 ± 1.3 mg/dl, respectively, in controls. All differences were statistically significant (P ≤ 0.0001). Stepwise logistic regression analysis, including sex, BMI, triglycerides, total cholesterol, and glucose as covariates, revealed that MGD was significantly associated with higher blood levels of total cholesterol (OR, 1.07; 95% confidence interval [CI], 1.04-1.09; P < 0.001). Likewise, MGD was found to be significantly associated with increased blood levels of LDL (OR, 1.07; 95% CI, 1.04-1.09; P < 0.001) and HDL (OR, 1.11; 95% CI, 1.06-1.17; P < 0.001). CONCLUSIONS: The results suggest that young and middle-aged patients with MGD with no history of hypercholesterolemia may have higher blood cholesterol levels than controls of similar age without MGD. If this finding is confirmed by larger studies, MGD may become a marker of previously unknown hypercholesterolemia and ophthalmologists may increase their role in the early detection of an important risk factor for cardiovascular disease.

[Epidemiologic studies on the health status of the population living in the Sacco River Valley]. / Indagini epidemiologiche sullo stato di salute della popolazione residente nell'area della Valle del Sacco.

UNLABELLED: OBIETTIVO: to analyze the health status of the population living in an area close to the Colleferro industrial plant. SETTING AND PARTICIPANTS: the area of the Sacco River Valley, Central Italy nearby Rome, has been heavily polluted over the years by industrial wastes deriving from the chemical industrial plant in Colleferro. In 2006, it was discovered that the herds of livestock were contaminated by beta-hexachlorocycloexane (ß-HCH, an industrial waste belonging, as well as lindane, to the group of hexachlorocycloexane isomers). MAIN OUTCOME MEASURES: the analyses of mortality and morbidity were carried out for the 1998-2007 period (calculation of standardized mortality ratios, SMR), and for the period 2003-2007 (calculation of standardized hospitalization ratios, SHR), respectively. The general population in the Lazio Region has been considered as reference. In addition, a biomonitoring study was conducted on a sample of the population living in 4 areas of the Sacco River Valley with different levels of exposure and the following persistent organic pollutants were measured in the blood (α, ß and γ-HCH, HCB p,p'-DDT and p,p'- DDE, 6 NDL-PCB congeners and 12 DL-PCBs, PCDDs and PCDFs), and heavy metals (Cd, Hg, Pb). RESULTS: cancer mortality in men was increased in the area (SMR=1.20), especially for specific cancer sites (stomach, larynx, lungs, pleura, myeloma); in women an excess of mortality from diabetes was detected (SMR=1.44). The analysis of morbidity indicated an excess of hospitalization for various cancers (larynx, myeloma) in men, for respiratory illness and asthma in both genders and for thyroid disease in women. The biomonitoring study found high mean concentration of ß-HCH (mean: 99.05 ng/g fat, SD=121.3), with higher levels in the population living along the river (mean=150 ng/g fat; SD=153.5), likely occurred through water and local food. CONCLUSION: the area of Colleferro has been polluted by multiple sources and the human population has been exposed to industrial chemicals, toxic substances in the workplace, and to the cumulative accumulation of organic pesticides especially through water and food.