The prokinetic levosulpiride elevates vasoinhibin levels in the vitreous of patients with proliferative diabetic retinopathy (PDR) suggesting clinical benefits due to the anti-vasopermeability and ...anti-angiogenic properties of vasoinhibin. We investigated the biological activity of levosulpiride in centre-involving diabetic macular oedema (DME).
Prospective, randomized, double-blinded, dual-centre, phase 2 trial in patients with centre-involving DME orally treated with placebo (n = 17) or levosulpiride (n = 17) for 8 weeks or in patients with PDR undergoing elective pars plana vitrectomy and receiving placebo (n = 18) or levosulpiride (n = 18) orally for the 1 week before vitrectomy.
Levosulpiride improved changes from baseline in best-corrected visual acuity (p ≤ 0.037), central foveal thickness (CFT, p ≤ 0.013), and mean macular volume (MMV, p ≤ 0.002) at weeks 4, 6, and 8 compared to placebo. At 8 weeks, the proportion of eyes gaining ≥5 ETDRS letters at 4 m (41% vs. 28%), losing ≥21 μm in CFT (55% vs. 28%), and dropping ≥0.06 mm
in MMV (65% vs. 29%) was higher after levosulpiride than placebo. The overall grading of visual and structural parameters improved with levosulpiride (p = 0.029). Levosulpiride reduced VEGF (p = 0.025) and PlGF (p = 0.008) levels in the vitreous of PDR patients. No significant adverse side-effects were detected.
Oral levosulpiride for 8 weeks improved visual and structural outcomes in patients with centre-involving DME by mechanisms that may include intraocular upregulation of vasoinhibin and downregulation of VEGF and PlGF. Larger clinical trials evaluating long-term efficacy and safety are warranted.
PRéCIS:: Intraocular pressure (IOP) measurement differences with Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) are affected by atmospheric pressure inside a hyperbaric ...chamber.
To compare IOP measurements obtained with GAT and DCT in 22 normal individuals at different atmospheric pressures simulated in a hyperbaric chamber.
The IOP of both eyes of 22 healthy volunteers was measured using GAT and DCT at 4 different atmospheric pressure levels.Starting at 1 Queretaro atmospheric pressure (QATM), the IOP was measured with GAT and DCT. The atmospheric pressure was then increased to 1.1 QATM (equivalent to 1032 m above sea level), 1.2 QATM (equivalent to 315 m above sea level), and 1.25 QATM (equivalent to sea level), starting 5 minutes after reaching each level. The limits of agreement between various measurements with each tonometer were calculated using the Bland-Altman plots.
The first 4 subjects were used to measure feasibility, consistency, variability, and the time needed for IOP to return to baseline after each atmospheric pressure increase.For the entire 44 eyes, the mean GAT IOP at 1 QATM was 12.23 mm Hg (range, 8 to 20 mm Hg; SD, 2.84) and mean DCT was 16.36 (range, 12.1 to 25.3; SD, 2.84), with a mean 4.14 mm Hg difference (range, -0.1 to 7.5 mm Hg; SD, 1.62; P<0.001).Using the second measurements of the first 4 subjects and those after 5 minutes of adaptation for the rest of the group at 1.1 QATM, mean GAT IOP was 11.05±2.68 mm Hg and mean DCT IOP was 15.60±3.02 mm Hg, for a mean difference between instruments of 4.56±1.81 mm Hg (P<0.001).At 1.2 QATM, mean GAT IOP was 11.14±2.53 mm Hg and mean DCT IOP was 15.39±2.91 mm Hg. The difference between instruments was 4.25±2.12 mm Hg (P<0.001).At 1.25 QATM, the mean GAT IOP was 12.39±3.11 mm Hg and mean DCT IOP was 14.91±2.73 mm Hg. The difference between instruments after 5 minutes of adaptation was 2.53±1.62 mm Hg (P<0.001).Generalized estimating equations for performing linear regression multivariable analysis using atmospheric pressure, expressed as altitude, and age as covariates, shows that the difference between GAT and DCT increases by 1 mm Hg per 673 m of increase of altitude above sea level. Age was not a significant predictor.
Acute changes in atmospheric pressure induce changes in IOP measurements for both GAT and DCT and in different directions. Despite the limitation of sample size, it may be postulated that the difference of IOP measurements between the 2 tonometers increases with lower atmospheric pressures.
BackgroundNo comprehensive study currently exists on the supply of ophthalmologists across Latin America. We explored sociogeographic inequalities in the availability and distribution of ...ophthalmologists across 14 Latin American countries.MethodsThe National Ophthalmologic Societies of Argentina, Bolivia, Brazil, Colombia, Costa Rica, Chile, the Dominican Republic, Ecuador, Guatemala, Mexico, Paraguay, Peru, Uruguay and Venezuela provided data on affiliated ophthalmologists by first-order subnational divisions in 2013. Human Development Index (HDI) estimates at the corresponding subnational division were used as equity stratifiers. Distributional inequality of ophthalmologists within each country was assessed by the health concentration index (HCI) and the index of dissimilarity (ID), along with the mean level of ophthalmologists per population.ResultsAcross all countries studied, there were 5.2 ophthalmologists per 100 000 population on average (95% CI 5.0 to 5.4) in 2013, with a mean HCI of 0.26 (0.16 to 0.37) and a mean relative ID of 22.7% (20.9% to 24.7%). There was wide inequality in ophthalmologist availability between countries, ranging from 1.2 (1.1 to 1.4) in Ecuador to 8.6 (8.5 to 8.8) in Brazil. All countries had positive (ie, pro-rich) HCI values ranging from 0.68 (0.66 to 0.71) in Guatemala to 0.02 (−0.11 to 0.14) in Venezuela. Correspondingly, redistributive potential to achieve equity was closest in Venezuela (ID: 1.5%) and farthest in Guatemala (ID: 60.3%). Benchmarked against regional averages, most countries had a lower availability of ophthalmologists and higher relative inequality.ConclusionsThere is high inequality in the level and distribution of ophthalmologists between and within countries in Latin America, with a disproportionate number concentrated in more developed, socially advantaged areas. More equitable access to ophthalmologists could be achieved by implementing incentivised human resources redistribution programmes and by improving the social determinants of health in underserved areas.
Diabetic retinopathy (DR) and diabetic macular edema (DME) are potentially blinding, microvascular retinal diseases in people with diabetes mellitus. Preclinical studies support a protective role of ...the hormone prolactin (PRL) due to its ocular incorporation and conversion to vasoinhibins, a family of PRL fragments that inhibit ischemia-induced retinal angiogenesis and diabetes-derived retinal vasopermeability. Here, we describe the protocol of an ongoing clinical trial investigating a new therapy for DR and DME based on elevating the circulating levels of PRL with the prokinetic, dopamine D2 receptor blocker, levosulpiride.
It is a prospective, randomized, double-blind, placebo-controlled trial enrolling male and female patients with type 2 diabetes having DME, non-proliferative DR (NPDR), proliferative DR (PDR) requiring vitrectomy, and DME plus standard intravitreal therapy with the antiangiogenic agent, ranibizumab. Patients are randomized to receive placebo (lactose pill, orally TID) or levosulpiride (75 mg/day orally TID) for 8 weeks (DME and NPDR), 1 week (the period before vitrectomy in PDR), or 12 weeks (DME plus ranibizumab). In all cases the study medication is taken on top of standard therapy for diabetes, blood pressure control, or other medical conditions. Primary endpoints in groups 1 and 2 (DME: placebo and levosulpiride), groups 3 and 4 (NPDR: placebo and levosulpiride), and groups 7 and 8 (DME plus ranibizumab: placebo and levosulpiride) are changes from baseline in visual acuity, retinal thickness assessed by optical coherence tomography, and retinal microvascular abnormalities evaluated by fundus biomicroscopy and fluorescein angiography. Changes in serum PRL levels and of PRL and vasoinhibins levels in the vitreous between groups 5 and 6 (PDR undergoing vitrectomy: placebo and levosulpiride) serve as proof of principle that PRL enters the eye to counteract disease progression. Secondary endpoints are changes during the follow-up of health and metabolic parameters (blood pressure, glycated hemoglobin, and serum levels of glucose and creatinine). A total of 120 patients are being recruited.
This trial will provide important knowledge on the potential benefits and safety of elevating circulating and intraocular PRL levels with levosulpiride in patients with DR and DME.
Ethics approval has been obtained from the Ethics Committees of the National University of Mexico (UNAM) and the Instituto Mexicano de Oftalmología, I.A.P. Dissemination will include submission to peer-reviewed scientific journals and presentation at congresses.
Registered at www.ClinicalTrials.gov, ID: NCT03161652 on May 18, 2017.
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.
Abstract Cataract is the primary cause of treatable blindness in low- and middle-income countries. Due to limited resources, the public sector often fails to provide adequate services, resulting in ...long waiting times, low quality or significant quantity gaps. Nonprofits are crucial in providing supplementary or complementary funding and resources for affordable eye care and other public goods and services. This study evaluates costs and benefits of cataract surgery at the nonprofit Mexican Institute of Ophthalmology (IMO) using data from interviews conducted in 2022 to estimate its social return. For every peso invested, the average stakeholder receives a 12:1 return in improved autonomy, self-confidence, and reduced stress levels. Sensitivity analysis suggests a SROI ratio of at least 2:1 in the most restrictive scenario, increasing to 33:1 under more lenient assumptions. Measuring and communicating the social value of nonprofit activities is critical for optimizing resource allocation, enhancing accountability, and generating valuable insights into their effectiveness.
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