Correlation between retinal vessel rarefaction and psychometric measures in an older Southern Italian population.

Objective: To explore the linear association between inner retinal layers thickness and macular capillary density compared to variations of global cognition evaluated by psychometric measures in a cohort of Mediterranean subjects aged 65+ years. Materials and methods: We performed a cross-sectional analysis of 574 participants aged 65 years+ drawn from a population-based Southern Italian study. All subjects underwent neurological evaluations, including global cognitive screening, the Mini-Mental State Examination (MMSE) and frontal assessment battery (FAB), together with an ophthalmic examination including optical coherence tomography (OCT) and OCT-Angiography. We assessed the average thickness of the ganglion cell complex (GCC) and the retinal nerve fiber layer (RNFL), the foveal avascular zone area, and vascular density (VD) of superficial (SVD) and deep (DVD) capillary plexi at the foveal and parafoveal area. Linear regression was applied to assess associations of ocular measurements with MMSE and FAB scores. Results: In the linear regression model, foveal DVD (beta = 0.01, 95% CI:0.004-0.052), whole DVD (beta = 0.04, 95% CI:0.02-0.08), and whole SVD (beta = 0.04, 95% CI:0.02-0.07) showed a positive association with MMSE. In addition, foveal SVD (beta = 0.01, 95% CI:0.003-0.05) and whole SVD (beta = 0.03, 95% CI:0.004-0.08) were positively associated with the FAB score. We found no further significant association between the MMSE score or the FAB score and the average thickness of the GCC and RNFL, and FAZ area. Conclusion: A direct linear association between the VD of the macular capillary plexi with global and frontal cognitive functions was observed in elderly subjects.

Association of Neuroretinal Thinning and Microvascular Changes with Hypertension in an Older Population in Southern Italy.

BACKGROUND: Retinal microvasculature assessment at capillary level may potentially aid the evaluation of early microvascular changes due to hypertension. We aimed to investigate associations between the measures obtained using optical coherence tomography (OCT) and OCT-angiography (OCT-A) and hypertension, in a southern Italian older population. METHODS: We performed a cross-sectional analysis from a population-based study on 731 participants aged 65 years+ subdivided into two groups according to the presence or absence of blood hypertension without hypertensive retinopathy. The average thickness of the ganglion cell complex (GCC) and the retinal nerve fiber layer (RNFL) were measured. The foveal avascular zone area, vascular density (VD) at the macular site and of the optic nerve head (ONH) and radial peripapillary capillary (RPC) plexi were evaluated. Logistic regression was applied to assess the association of ocular measurements with hypertension. RESULTS: GCC thickness was inversely associated with hypertension (odds ratio (OR): 0.98, 95% confidence interval (CI): 0.97-1). A rarefaction of VD of the ONH plexus at the inferior temporal sector (OR: 0.95, 95% CI: 0.91-0.99) and, conversely, a higher VD of the ONH and RPC plexi inside optic disc (OR: 1.07, 95% CI: 1.04-1.10; OR: 1.04, 95% CI: 1.02-1.06, respectively) were significantly associated with hypertension. CONCLUSION: A neuroretinal thinning involving GCC and a change in capillary density at the peripapillary network were related to the hypertension in older patients without hypertensive retinopathy. Assessing peripapillary retinal microvasculature using OCT-A may be a useful non-invasive approach to detect early microvascular changes due to hypertension.

Insulin Granule-Loaded MicroPlates for Modulating Blood Glucose Levels in Type-1 Diabetes.

Type-1 diabetes (T1DM) is a chronic metabolic disorder resulting from the autoimmune destruction of ß cells. The current standard of care requires multiple, daily injections of insulin and accurate monitoring of blood glucose levels (BGLs); in some cases, this results in diminished patient compliance and increased risk of hypoglycemia. Herein, we engineered hierarchically structured particles comprising a poly(lactic-co-glycolic) acid (PLGA) prismatic matrix, with a 20 × 20 µm base, encapsulating 200 nm insulin granules. Five configurations of these insulin-microPlates (INS-µPLs) were realized with different heights (5, 10, and 20 µm) and PLGA contents (10, 40, and, 60 mg). After detailed physicochemical and biopharmacological characterizations, the tissue-compliant 10H INS-µPL, realized with 10 mg of PLGA, presented the most effective release profile with ∼50% of the loaded insulin delivered at 4 weeks. In diabetic mice, a single 10H INS-µPL intraperitoneal deposition reduced BGLs to that of healthy mice within 1 h post-implantation (167.4 ± 49.0 vs 140.0 ± 9.2 mg/dL, respectively) and supported normoglycemic conditions for about 2 weeks. Furthermore, following the glucose challenge, diabetic mice implanted with 10H INS-µPL successfully regained glycemic control with a significant reduction in AUC0-120min (799.9 ± 134.83 vs 2234.60 ± 82.72 mg/dL) and increased insulin levels at 7 days post-implantation (1.14 ± 0.11 vs 0.38 ± 0.02 ng/mL), as compared to untreated diabetic mice. Collectively, these results demonstrate that INS-µPLs are a promising platform for the treatment of T1DM to be further optimized with the integration of smart glucose sensors.

Retinal Vascular Density on Optical Coherence Tomography Angiography and Age-Related Central and Peripheral Hearing Loss in a Southern Italian Older Population.

BACKGROUND: Age-related hearing loss (ARHL) and retinal vessel changes have both been associated to neurodegeneration/dementia, suggesting a possible link between these 2 conditions in older age. We aimed to determine whether superficial and deep vascular density (SVD and DVD) of the capillary plexi of macular vasculature can be associated with peripheral ARHL and age-related central auditory central processing (CAPD). METHOD: We analyzed data on 886 older participants (65 years+, age range: 65-92 years) in the cross-sectional population-based Salus in Apulia Study. Optical coherence tomography angiography was used to measure SVD and DVD of the capillary plexi of the macula at the 3-mm circle area centered on the fovea (whole retina), the parafoveal quadrant, and foveal quadrant. Disabling peripheral ARHL was defined as >40 dB hearing level of pure tone average on the frequencies from 0.5, 1, 2, and 4 KHz in the better ear, and age-related CAPD as <50% at the Synthetic Sentence Identification with Ipsilateral Competitive Message test in at least one ear. RESULTS: DVD at the whole retina and at the parafoveal quadrant were inversely associated only with age-related CAPD (odds ratio [OR]: 0.93, 95% confidence interval [CI]: 0.88-0.96 and OR: 0.94, 95 CI: 0.90-0.99, respectively). No further associations with peripheral ARHL were evident. CONCLUSIONS: Retinal vasculature is associated with central auditory processing pathology, possibly playing an important role in early detection and intervention. The association of retinal vascular density with age-related CAPD may bring us a further step forward in understanding the biological mechanisms underlying the links between neurodegeneration/dementia and ARHL.

Emerging Nano- and Micro-Technologies Used in the Treatment of Type-1 Diabetes.

Type-1 diabetes is characterized by high blood glucose levels due to a failure of insulin secretion from beta cells within pancreatic islets. Current treatment strategies consist of multiple, daily injections of insulin or transplantation of either the whole pancreas or isolated pancreatic islets. While there are different forms of insulin with tunable pharmacokinetics (fast, intermediate, and long-acting), improper dosing continues to be a major limitation often leading to complications resulting from hyper- or hypo-glycemia. Glucose-responsive insulin delivery systems, consisting of a glucose sensor connected to an insulin infusion pump, have improved dosing but they still suffer from inaccurate feedback, biofouling and poor patient compliance. Islet transplantation is a promising strategy but requires multiple donors per patient and post-transplantation islet survival is impaired by inflammation and suboptimal revascularization. This review discusses how nano- and micro-technologies, as well as tissue engineering approaches, can overcome many of these challenges and help contribute to an artificial pancreas-like system.

Timolol 0.1% gel versus timolol 0.5% eyedrops in the prophylaxis of ocular hypertension after phacoemulsification surgery.

PURPOSE: To determine the efficacy of timolol 0.1% gel in preventing increased intraocular pressure (IOP) after uncomplicated cataract surgery. METHODS: In this prospective, double-blinded, randomized study were enrolled 70 patients who underwent uncomplicated cataract surgery with phacoemulsification and intraocular lens implantation. After cataract surgery, 25 patients received a single instillation of timolol 0.1% gel (group A); 20 a single instillation of timolol 0.5% eyedrops (group B); and 25 no treatment (group C). The IOP was measured before surgery (T0) and 5 minutes (T1), 2 hours ± 30 minutes (T2), 4 hours ± 30 minutes (T3), and 24 hours ± 180 minutes after surgery (T4). RESULTS: The patients in groups A and B had lower mean IOP values than those in group C at T2, T3, and T4; IOP was higher at T2 and T3 than at T1 in the control group. The IOP spikes in group C were higher than those observed in groups A and B: at T2, they were observed in 40% of the patients in group A, 30% in group B, and 76% in group C; and at T3, in respectively 20%, 10%, and 68%; and at T4, in respectively 4%, 0%, and 28%. CONCLUSIONS: Timolol 0.1% gel is as effective as timolol 0.5% eyedrops in reducing IOP and in limiting the occurrence of IOP spikes for up to 24 hours after phacoemulsification.

Evaluation of the efficacy and safety of the ophthalmic insert Mydriasert in patients undergoing retinal angiography.

PURPOSE: To verify the efficacy to obtain mydriasis and cardiovascular safety of Mydriasert (ophthalmic insert containing tropicamide and phenylephrine) in diabetic and nondiabetic patients undergoing retinal angiography by comparing it with usually administered eyedrops (tropicamide 1% and phenylephrine 10%). METHODS: This was a prospective randomized study. A total of 154 eyes of 77 patients were randomly divided into 2 groups: group 1 consisted of 78 eyes, group 2 consisted of 76 eyes, and the patients were monitored for pupillary dilation, blood pressure, heart rate, and possible adverse effects at 0, 20, 40, 60, and 90 minutes. RESULTS: No severe adverse effects were observed in either group. In the entire sample studied, the mean pupillary diameter was greater in the eyedrops group after 20 and 40 minutes, while mydriasis was similar in the 2 groups after 60 minutes. The diabetic patients treated with Mydriasert had less mydriasis than those treated with eyedrops after 20 and 40 minutes, and diabetic patients showed less mydriasis than the nondiabetic patients after 60 and 90 minutes. There was no significant between-group difference in mean heart rate or systolic and diastolic blood pressure at any of the time points. CONCLUSIONS: Mydriasert assures an adequate degree of mydriasis for retinal angiography in both diabetic and nondiabetic patients. There are no differences in efficacy or safety between the insert and the usually administered eyedrops, but the low total drug dose administered with the insert reduces the risk of cardiovascular side effects.