Detection of insulin oligomeric forms by a novel surface plasmon resonance-diffusion coefficient based approach.

Insulin is commonly used to treat diabetes and undergoes aggregation at the site of repeated injections in diabetic patients. Moreover, aggregation is also observed during its industrial production and transport and should be avoided to preserve its bioavailability to correctly adjust glucose levels in diabetic patients. However, monitoring the effect of various parameters (pH, protein concentration, metal ions, etc.) on the insulin aggregation and oligomerization state is very challenging. In this work, we have applied a novel Surface Plasmon Resonance (SPR)-based experimental approach to insulin solutions at various experimental conditions, monitoring how its diffusion coefficient is affected by pH and the presence of metal ions (copper and zinc) with unprecedented sensitivity, precision, and reproducibility. The reported SPR method, hereby applied to a protein for the first time, besides giving insight into the insulin oligomerization and aggregation phenomena, proved to be very robust for determining the diffusion coefficient of any biomolecule. A theoretical background is given together with the software description, specially designed to fit the experimental data. This new way of applying SPR represents an innovation in the bio-sensing field and expanding the potentiality of commonly used SPR instruments well over the canonical investigation of biomolecular interactions.

Prevalence of diabetes and diabetic macular edema in patients undergoing senile cataract surgery in Italy: The DIabetes and CATaract study.

BACKGROUND: The purpose of this study is to determine the prevalence of diabetes and diabetic macular edema in patients undergoing senile cataract surgery in Italy. METHODS: It is a prospective, multicenter, cross-sectional study. Thirteen ophthalmic units equally distributed across the Italian territory have been involved in the study. For a period of 3 months, all subjects undergoing phacoemulsification received an Optical Coherence Tompgraphy (OCT) scan and were screened for the anamnestic presence of diabetes. In addition, five selected units collected blood samples from all their patients to measure glycated hemoglobin (HbA1c) levels and detect the presence of occult diabetes (HbA1c > 6.5%). In diabetic patients, levels of retinopathy were measured and diabetic macular edema was considered significant (clinically significant macular edema) when foveal thickness was above 30% of normal levels. RESULTS: A total number of 3657 subjects have been screened. Among them, 20.4% were diabetics. Prevalence of diabetes was significantly higher in males (24.7%) than in females (17%). Levels of HbA1c were tested in a representative sample of 1216 consecutive subjects, and occult diabetes was diagnosed in 4.8% of cases. No significant differences were observed between age groups or different geographic areas. Among diabetic patients, diabetic macular edema of any kind was present in 27.5% (clinically significant macular edema (6.6%)). No significant differences were seen in the prevalence of diabetic macular edema between males and females or between age groups. Among the 745 diabetic patients, no signs of retinopathy were seen in 537 subjects (76.3%), while 101 patients (14.3%) had nonproliferative retinopathy, 13 (1.7%) had nontreated proliferative diabetic retinopathy, and 53 (7.5%) had laser-treated retinopathy. In the entire sample of 3657 subjects, a normal macula was present in 90.9% of cases, diabetic macular edema of any kind in 5.4%, and other maculopathies in 3.4%. CONCLUSION: In this large cohort study on patients undergoing cataract surgery, more than one-fourth were diabetics and more than one-fourth of these had diabetic macular edema. These high prevalences suggest the opportunity to plan an adequate preoperative assessment in all patients in order to reduce the risk of postoperative development or worsening of a sight-threatening complication such as chronic diabetic macular edema.

Eplerenone Versus Observation in the Treatment of Acute Central Serous Chorioretinopathy: A Retrospective Controlled Study.

INTRODUCTION: To investigate the effects of eplerenone compared to observation in the treatment of acute central serous chorioretinopathy (CSC). METHODS: Charts of consecutive patients with a diagnosis of acute CSC (visual symptoms < 12 weeks) were reviewed. Included patients were divided into a treatment group (treated with eplerenone) and a control group (observation). Main outcome measures included changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), height of subretinal fluid (SRF) and subfoveal choroidal thickness (CT) at 1 and 3 months in the two groups. RESULTS: Fifteen eyes of 15 patients (2 female, 13 male) and 12 eyes of 12 patients (1 female, 11 male [p = 1.000]) were included in the treatment and control groups, respectively. The mean age was 44 ± 9 (30-65) and 47 ± 11 years (28-66 years, p = 0.493), respectively. In the treatment group, BCVA improved significantly at 1 month (p = 0.018) and 3 months of follow-up (p = 0.011), while a non-significant improvement was seen in the control group. At 3 months, 12 of 15 eyes (80%) in the treatment group demonstrated complete SRF resolution, versus 3 of 12 eyes (25%) in the control group (p = 0.007). In the treatment group, SRF and CMT were significantly reduced at the 1-month follow-up (p = 0.014, p = 0.028, respectively) and the 3-month follow-up (p < 0.001 for both analyses), while in the control group the changes were not statistically significant. Eplerenone was well tolerated in all patients. CONCLUSION: Patients affected by acute CSC treated with eplerenone achieved greater and faster resolution of the disease compared to the observation group. Eplerenone may represent an attractive new first-line treatment option for acute CSC.

Pharmacotherapy of Central Serous Chorioretinopathy: A Review of the Current Treatments.

BACKGROUND: Central serous chorioretinopathy (CSC) is the fourth most frequent retinal disorder in terms of prevalence. It typically occurs in young subjects and affects men more often than women. CSC is characterized by serous retinal detachment (SRD) involving mainly the macular area. The clinical course is usually selflimited, with spontaneous resolution within 3 months. The persistence of SRD or multiple relapse may result in a chronic form of CSC distinguished by permanent retinal pigment epithelium (RPE) and photoreceptor damage. As the pathogenetic mechanism of CSC primarily involves RPE and choroidal vascularization, the current therapeutic approaches aim to restore the normal functions of RPE and normal choroidal vascular permeability. In this review, the authors aim to summarize the current therapeutic approach to CSC. METHODS: A comprehensive review of the literature was conducted in PubMed by searching for relevant studies on the current therapeutic options for CSC, including simple observation, conventional laser treatment, subthreshold laser treatment (SLT), photodynamic therapy (PDT) with verteporfin, treatment with mineralocorticoid receptor (MR) antagonists and treatment with anti-vascular endothelial growth factor drugs. RESULTS: Since most cases resolve spontaneously, the most common initial CSC treatment is observation. Current evidence suggests that PDT and SLT are valuable in improving visual acuity, reducing subretinal fluid and maintaining long-term effectiveness. No clear evidence of efficacy has been achieved for anti-VEGF. MR antagonists might be a viable choice for the treatment of chronic CSC. CONCLUSION: The pathophysiology of CSC remains poorly understood and as a consequence, the gold standard of care for CSC is yet to be defined. To date, PDT and SLT continue to offer good clinical outcomes. Positive preliminary results seem to emerge from the studies of MR antagonists.

FACTORS INFLUENCING VISUAL ACUITY IN PATIENTS RECEIVING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR MYOPIC CHOROIDAL NEOVASCULARIZATION.

PURPOSE: To identify the prognostic variables relative to myopic choroidal neovascularization (CNV) treated with intravitreal ranibizumab/bevacizumab. METHODS: Forty-eight patients with myopic CNV were enrolled in a prospective, interventional, non-randomized 12-month study. Intravitreal ranibizumab/bevacizumab was administered in a pro-re-nata regimen and re-treatment was performed in the presence of angiographic leakage, intraretinal/subretinal fluid on optical coherence tomography, new hemorrhages, five-letter decrease and increased metamorphosia. The primary outcome measures were the identification of the predictive value of symptom duration, patient's age, refractive error, best-corrected visual acuity (BCVA), central macular thickness (CMT), CNV area, CNV location, retinal hemorrhages, atrophy, lacquer cracks, and CNV-fundus autofluorescence pattern (hyper-fundus autofluorescence/patchy pattern). The secondary outcomes were patients requiring either one or two injections to achieve CNV stabilization. RESULTS: The mean BCVA improved from 0.49 ± 0.30 (logarithm of minimal angle resolution, Snellen equivalent 20/63) to 0.39 ± 0.32 (20/49) at 1-year follow-up (P = 0.043). Univariate and multiple stepwise linear regression analysis identified baseline BCVA (P = 0.0003), symptom duration (P = 0.005), CMT (P = 0.02), and fundus autofluorescence pattern (P = 0.005) as the explanatory variables on the final BCVA and the change in the mean BCVA. Overall, patients with better baseline BCVA, early diagnosis, lower CMT, or disclosing a hyperfundus autofluorescence CNV pattern achieved better visual outcomes. Patients responding with just one to two intravitreal injections (45.8%) obtained better visual outcomes compared with patients receiving three or more injections, and this group consisted of younger patients with lesser CMT, smaller CNV area, and fewer baseline hemorrhages. CONCLUSION: Ranibizumab/bevacizumab therapy was effective in improving and maintaining visual acuity in myopic choroidal neovascularization. Early diagnosis, better baseline BCVA, and hyperfundus autofluorescence CNV pattern were strongly associated with better functional outcomes. Moreover, CNV distinguished by its small size and low CMT responded more favorably, achieving a better visual outcome.

Retreatment with Ozurdex for macular edema secondary to retinal vein occlusion.

PURPOSE: To review the current practice of retreatment with Ozurdex injections in patients with macular edema (ME) secondary to retinal vein occlusion (RVO), and to recommend simple guidelines for Ozurdex reinjection in management of RVO. METHODS: This was a multicenter retrospective study of patients who received more than 2 Ozurdex injections for the treatment of ME in RVO. Recorded parameters included percent of patients with a 15-letter gain, visual acuity (VA) improvement from baseline, change in central macular thickness (CMT), time to reinjection, and occurrence of any complications. RESULTS: A total of 128 patients were included, 58 (45.3%) with central RVO (CRVO) and 70 (54.7%) with branch RVO (BRVO). Mean interval for Ozurdex reinjection was 5.9 months following the first injection and 8.7 months following the second. A >15-letter gain in VA was observed in 34 (48.8%) patients with CRVO and 16 (28%) patients with BRVO. Mean overall VA improvement at month 6 did not show significance (p>0.05); however, a significantly better mean VA improvement was seen in treatment-naïve eyes (p<0.03). The CMT was significantly reduced compared to baseline. The mean CMT decreased by 214.6 µm in eyes with BRVO (n = 53) and by 355.1 µm in eyes with CRVO (n = 63) (p = 0.002). Complication rates were very low. CONCLUSIONS: Repeated injections of Ozurdex are effective and have a favorable safety profile. In current practice, the retreatment interval with Ozurdex injections might be too long, precluding the full therapeutic potential of this treatment modality. A strategy for managing RVO patients treated with Ozurdex on an as-needed basis is provided.