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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.

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, but existing methods are insufficient to screen early risk factors of diabetic retinopathy (DR). Here, we introduce non-evoked ERG as a simple, fast modality to record spontaneous activity, from which we developed a single random forest-based model that predicts disease cases in rodent models of obesity and in people with overweight, obesity, and metabolic syndrome. Classification performance was validated using a dataset from an independent eye center. Our algorithm can be coupled with different ERG sensors, including ones working with portative, non-mydriatic devices. Principal component and discriminant analysis suggest slow spontaneous ERG frequencies as main discriminators for our predictive model. Our study will facilitate the implementation of interventions for the prevention of overweight and obesity by providing a robust, quantitative, and non-invasive identification and follow-up approach, which should ultimately reduce DR incidence.

Objective To determine normal macular thickness values in a healthy Mexican population and its variation by age and gender using Huvitz spectral-domain optical coherence tomography (HOCT-1F). Methods This cross-sectional study included 211 consecutive eyes from clinically normal subjects (66 men, 145 women) between October 2018 and December 2018, with best-corrected visual acuities better than 20/30. One eye was selected for the macular scan using the Huvitz OCT (Huvitz OCT-1F, HOCT-1F, Huvitz Co., Ltd., Republic of Korea) with an automated segmentation algorithm. Three vertical and horizontal scans, centered on the fovea with an area of 9 mm, and a color 45° fundus photograph were obtained using Huvitz OCT-1F. Macular measurements were presented as means with standard deviations values for each of the nine regions defined by the Early Treatment Diabetic Retinopathy Study (ETDRS). Results The mean age was 34.3±11.9 years. Using the ETDRS map, the mean central subfield thickness (CST) was 227.4±18.9 µm. Male gender was associated with greater CST (P

Purpose: This is a case report of a male patient who suffered a high-voltage electrical burn and presented with bilateral pigmentary retinopathy. Methods: A 40-year-old man presented with bilateral vision loss following a high-voltage electrical injury sustained 10 years earlier. Family history, ocular history, and anterior segment evaluation were unremarkable. Results: Fundus examination revealed bilateral optic disc pallor, widespread areas of chorioretinal atrophy, and pigmentary changes surrounding the optic disc that partially involved the macula with some spared areas located on the superior retina. Conclusions: Retinal manifestations following a high-voltage electrical injury can resemble other hereditary and inflammatory diseases with similar clinical patterns, therefore, a meticulous family, medical, and clinical evaluation is essential.

Purpose: To analyze the macular ganglion cell-inner plexiform and retinal nerve fiber layer thicknesses after vitrectomy with the inverted flap technique for idiopathic macular holes. Methods: A prospective study was conducted on 28 eyes treated with surgery for idiopathic macular holes. The inverted internal limiting membrane flap technique assisted with Brilliant Blue staining (0.05%) was performed. Ophthalmologic examinations and quantitative analysis of the macular ganglion cell complex thickness were performed at baseline,1 and 3 months after surgery. Results: The preoperative mean thicknesses of the ganglion cell-inner plexiform layer and ganglion cell-inner plexiform layer + retinal nerve fiber layer were 88.9 and 124.8 µm, respectively. The mean ganglion cell-inner plexiform layer thicknesses at 1 and 3 months after surgery were reduced to 72.8 and 65.2 µm, respectively (p

This study aimed to compare clinical efficacy of retinal laser photocoagulation using a 577-nm multi-spot laser with pulses of 20 ms versus conventional 532-nm single-spot laser treatment with pulses of 100 ms, on the same patient with proliferative diabetic retinopathy (PDR) during 6-weeks follow-up. We included 46 eyes of patients treated at the retina service of the Mexican Institute of Ophthalmology, Queretaro, Mexico. Pan-retinal photocoagulation (PRP) was performed on one eye (Group 1) using multi-spot PRP with the EasyRet® 577 diode laser (Quantel Medical, Cournon d’Auvergne, France). On the other eye (Group 2), laser treatment was performed by the conventional single spot method using the Oculight SL® 532 diode laser (IRIDEX Corporation, Mountain View, CA, The USA). The primary endpoint was absence of signs in which the disease was considered active at 6 weeks and the secondary outcomes included laser parameters, best-corrected visual acuity (BCVA), central macular thickness (CMT) at baseline, and 6 weeks and results of subjective pain analysis. There was no significant difference between both treatment groups regarding age, gender, BCVA or CMT at baseline. At 6 weeks, PDR activity was similar between the groups (47.8 % versus 56.5%; p =0.55). No significant difference in CMT and BCVA was observed between the groups throughout the study period. Patient-reported pain scores were similar between the groups (5.0 versus 5.8; p = 0.30). However, total time of procedure was significantly shorter in group 1 (12.9 minutes [min] versus 22.3 min; p < 0.001). No major adverse events were identified We concluded that laser photocoagulation of the retina with the use of the multi-spot technology in patients with PDR has similar short-term efficacy to that of conventional single spot retinal photocoagulation. The multi-spot laser required less time to complete the procedure with more spots delivered to compensate its lower fluency, showing similar patient tolerance.

Purpose: This work examines the relationship between first- and third-month anatomical and visual response with antivascular endothelial growth factor for diabetic macular edema. Methods: We prospectively evaluated 58 eyes with center-involved diabetic macular edema. Response was categorized upon the anatomical status after 3 monthly doses based on the reduction of central macular thickness (CMT) from baseline (≥20% or not). Correlation analysis between the anatomical response status, gained letters, optical coherence tomography morphological features, and other baseline characteristics were obtained. Results: Twenty-five eyes (43.1%) achieved an anatomical reduction of ≥20% at the third month. Those with a reduction of ≥20% of CMT had subretinal fluid ( P < .01), lower hemoglobin A1c values ( P < .01), lower proportion of intraretinal cysts ( P < .01), a greater anatomical reduction, and visual improvement at the first month of treatment. Multiple logistic regression analysis, showed that the change of CMT after the first injection was an independent predictor for the anatomical reduction of ≥20% after the loading phase ( P < .05). Best corrected visual acuity gain after the first dose showed a significant association with an improvement of ≥10 letters after the loading phase ( P < .05), but not for macular thickness reduction. Conclusions: First month anatomical reduction was associated with the anatomical response at 3 months ( P = .042) after monthly ranibizumab therapy. Visual improvement at the first month was predictive only for the visual outcome after the 3 monthly doses ( P = .032).

Objective To determine normal macular thickness values in a healthy Mexican population and its variation by age and gender using Huvitz spectral-domain optical coherence tomography (HOCT-1F). Methods This cross-sectional study included 211 consecutive eyes from clinically normal subjects (66 men, 145 women) between October 2018 and December 2018, with best-corrected visual acuities better than 20/30. One eye was selected for the macular scan using the Huvitz OCT (Huvitz OCT-1F, HOCT-1F, Huvitz Co., Ltd., Republic of Korea) with an automated segmentation algorithm. Three vertical and horizontal scans, centered on the fovea with an area of 9 mm, and a color 45° fundus photograph were obtained using Huvitz OCT-1F. Macular measurements were presented as means with standard deviations values for each of the nine regions defined by the Early Treatment Diabetic Retinopathy Study (ETDRS). Results The mean age was 34.3±11.9 years. Using the ETDRS map, the mean central subfield thickness (CST) was 227.4±18.9 µm. Male gender was associated with greater CST (P

Purpose High circulating levels of the hormone prolactin (PRL) protect against experimental diabetic retinopathy (DR) due to the retinal accumulation of vasoinhibin, a PRL fragment that inhibits blood vessel permeability and growth. A phase 2 clinical trial is investigating a new therapy for DR based on elevating serum PRL levels with levosulpiride, a prokinetic dopamine D2 receptor blocker. Here, we tested whether levosulpiride-induced hyperprolactinemia elevates PRL and vasoinhibin in the vitreous of volunteer patients with proliferative DR (PDR) undergoing elective pars plana vitrectomy. Methods Patients were randomized to receive placebo (lactose pill, orally TID; n = 19) or levosulpiride (25 mg orally TID; n = 18) for the 7 days before vitrectomy. Vitreous samples from untreated non-diabetic (n = 10) and PDR (n = 17) patients were also studied. Results Levosulpiride elevated the systemic (101 ± 13 [SEM] vs. 9.2 ± 1.3 ng/mL, P < 0.0001) and vitreous (3.2 ± 0.4 vs. 1.5 ± 0.2 ng/mL, P < 0.0001) levels of PRL, and both levels were directly correlated (r = 0.58, P < 0.0002). The vitreous from non-diabetic patients or from PDR patients treated with levosulpiride, but not from placebo-treated PDR patients, inhibited the basic fibroblast growth factor (bFGF)- and vascular endothelial growth factor (VEGF)-induced proliferation of endothelial cells in culture. Vasoinhibin-neutralizing antibodies reduced the vitreous antiangiogenic effect. Matrix metalloproteases (MMPs) in the vitreous cleaved PRL to vasoinhibin, and their activity was higher in non-diabetic than in PDR patients. Conclusions Levosulpiride increases the levels of PRL in the vitreous of PDR patients and promotes its MMP-mediated conversion to vasoinhibin, which can inhibit angiogenesis in DR. Translational Relevance These findings support the potential therapeutic benefit of levosulpiride against vision loss in diabetes.

Determining the precise location of intraocular foreign bodies is crucial for the management of patients with open-globe injury. Computed tomography is the most common method for detecting intraocular foreign bodies in the posterior segment. In this article, we describe three cases of open-globe injury with different types of intraocular foreign bodies in the posterior segment that were accurately located using computed tomography scans and B-scan ultrasonography.Each of the three cases of open-globe injury described in this report had different types of ocular trauma, clinical symptoms, and intraocular foreign bodies. Computed tomography scans showed the exact location of the intraocular foreign bodies in the posterior segment in two of the three cases. A B-scan ultrasound was used to determine the location of a non-metallic intraocular foreign body in the third case. All three patients had intraocular foreign bodies, and one of them had an additional orbital foreign body. Case 1 had a perforating eye injury with the additional intraorbital foreign body; Cases 2 and Case 3 had different types of intraocular foreign bodies and prognoses. Various treatment approaches were used, ranging from observation to surgery, depending on the location of the intraocular foreign bodies, and all cases were successfully managed. These three cases show that proper use of various types of imaging tests is indispensable in the context of an intraocular foreign body related to open-globe injury.Imaging techniques are crucial for the detection of an intraocular foreign body, and computed tomography is one of the simplest and most useful, especially in cases of open-globe injury.La ubicación precisa de un cuerpo extraño intraocular es crucial para el manejo de pacientes con trauma ocular abierto. La tomografía computarizada se usa habitualmente para detectar su ubicación en el segmento posterior. Reportamos tres casos con diferentes cuerpos extraños intraoculares en el segmento posterior, que fueron localizados con precisión mediante la tomografía computarizada y ecografía modo B.Presentamos tres casos con diferentes mecanismos de trauma, tipos de cuerpo extraño intraocular, síntomas clínicos y pronóstico visual. La tomografía computarizada determinó la ubicación exacta de todos los cuerpos extraños intraoculares en el segmento posterior. El ultrasonido modo B se realizó en un paciente con un cuerpo extraño intraocular no metálico. El primer caso tuvo una lesión ocular perforante con un cuerpo extraño intraorbitario; el caso dos y el caso tres presentaron diferentes tipos de cuerpos extraños intraoculares con pronóstico diferente. El manejo y el pronóstico fue distinto en todos los casos; todos se manejaron con éxito. La ubicación exacta de los cuerpos extraños intraoculares utilizando las diferentes modalidades de diagnóstico es importante en estos pacientes. Estos casos sirven como recordatorio de que el uso adecuado de las pruebas de imagen es indispensable en el contexto de un cuerpo extraño intraocular relacionado con trauma ocular abierto.Las diferentes técnicas de imágenes son muy importantes para la detección de un cuerpo extraño intraocular. La tomografía computarizada es una de las modalidades de imagen más simple y efectiva para la localización de cuerpos extraños intraoculares relacionadas con trauma ocular abierto.

Background 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. Methods 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. Discussion 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 and dissemination 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. Clinical trial registration Registered at www.ClinicalTrials.gov, ID: NCT03161652 on May 18, 2017.

The prolactin/vasoinhibin axis defines an endocrine system, in which prolactin (PRL) and vasoinhibins regulate blood vessel growth and function, the secretion of other hormones, inflammatory and immune processes, coagulation, and behavior. The core element of the PRL/vasoinhibin axis is the generation of vasoinhibins, which consists in the proteolytic cleavage of their precursor molecule PRL. Vasoinhibins can interact with multiple different partners to mediate their effects in various tissues and anatomical compartments, indicating their pleiotropic nature. Based on accumulating knowledge about the PRL/vasoinhibin axis, two clinical trials were initiated, in which vasoinhibin levels are the target of therapeutic interventions. One trial investigates the effect of levosulpiride, a selective dopamine D2-receptor antagonist, on retinal alterations in patients with diabetic macular edema and retinopathy. The rationale of this trial is that the levosulpiride-induced hyperprolactinemia resulting in increased retinal vasoinhibins could lead to beneficiary outcomes in terms of a vasoinhibin-mediated antagonization of diabetes-induced retinal alterations. Another trial investigated the effect of bromocriptine, a dopamine D2-receptor agonist, for the treatment of peripartum cardiomyopathy. The rationale of treatment with bromocriptine is the inhibition of vasoinhibin generation by substrate depletion to prevent detrimental effects on the myocardial microvascularization. The trial demonstrated that bromocriptine treatment was associated with a high rate of left ventricular recovery and low morbidity and mortality. Therapeutic interventions into the PRL/vasoinhibin axis bear the risk of side effects in the areas of blood coagulation, blood pressure, and alterations of the mental state.