Levosulpiride for the treatment of diabetic macular oedema: a phase 2 randomized clinical trial.

BACKGROUND/OBJECTIVE: 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). PATIENTS/METHODS: 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. RESULTS: 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 mm3 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. CONCLUSIONS: 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.

Preventable risk factors for type 2 diabetes can be detected using noninvasive spontaneous electroretinogram signals.

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.

Progressive Massive Choroidal Neovascularization, an Aggressive Phenotype: Case Report.

We report 2 cases of an aggressive choroidal neovascularization phenotype. A 77-year-old hypertensive woman, with a 4-year history of visual loss in her left eye, due to vitreous hemorrhage associated with a dome-shaped mass lesion underwent pars plana vitrectomy. An extensive subretinal hemorrhage was found, associated with extensive subretinal fibrosis, which was treated with endophotocoagulation and intravitreal injection of anti-VEGF. Best-corrected visual acuity after surgery was light perception. A 74-year-old woman with a 4-year history of treatment for choroidal neovascularization in both eyes presented with an extensive subretinal hemorrhage associated with exudation in the temporal peripheral retina. Lesions became larger despite monthly intravitreal anti-VEGF injections (14 injections) and verteporfin photodynamic therapy in both eyes. Throughout the years, the choroidal neovascular lesion continued to enlarge until it developed a severe vitreous hemorrhage. The patient rejected treatment and ended up with no light perception at the end of the follow-up (8 years). A rare severe choroidal neovascularization phenotype is presented here and would be considered to be at the aggressive extreme of the spectrum of a neovascular age-related macular degeneration or polypoidal choroidal vasculopathy that presents massive hemorrhage and exudation as much as in the posterior pole as in the peripheral retina.

Macular ganglion cell complex thickness after vitrectomy with the inverted flap technique for idiopathic macular holes.

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<0.001 and p<0.001, respectively). The mean postoperative ganglion cell-inner plexiform layer + retinal nerve fiber layer thickness was also reduced at 1 and 3 months (108.8 and 99.3 µm, respectively; p<0.001 and p<0.001, respectively). No significant difference was found between the preoperative and postoperative best-corrected visual acuities at 1 and 3 months (p<0.73 and p<0.14, respectively). CONCLUSION: The macular ganglion cell-inner plexiform layer and ganglion cell-inner plexiform layer + retinal nerve fiber layer thicknesses were significantly reduced after vitrectomy with the inverted flap technique assisted with Brilliant Blue staining (0.05%) for idiopathic macular holes.

Micropulse laser in patients with refractory and treatment-naïve center-involved diabetic macular edema: short terms visual and anatomic outcomes.

PURPOSE: The purpose of the study is to describe visual and anatomic outcomes of 5774nm micropulse laser photocoagulation in eyes with either treatment-naïve or refractory diabetic macular edema (DME) at 3 months. METHODS: This was a prospective case series that recruited 23 consecutive patients (33 eyes) with center-involved DME that was either treatment-naïve or had not responded to prior treatment. Micropulse therapy was performed with the Easy Ret 577 (Quantel Medical, Cournon d'Auvergne, France) diode laser in a high-density manner in eyes with treatment-naïve or refractory DME. The primary outcome was the change of best-corrected visual acuity (BCVA; logMAR) at 1 and 3 months. Secondary outcomes were changes in the central macular thickness (CMT), thickness area, macular volume, and macular capillary leakage at 1 and 3 months. RESULTS: There were no significant changes in BCVA at 3 months, with mean ± standard deviation (SD) of -0.08 ± 0.01 (p = 0.228) and + 0.01 ± 0.01 (p = 0.969) for treatment-naïve and refractory groups, respectively. The change in CMT at 3 months was statistically but not clinically significant in the treatment-naïve group only (mean ± SD; -30 ± 130 µm; p = 0.011). The macular volume and area thickness change were not statistically significant (p = 0.173 and p = 0.148 for macular volume and area thickness, respectively) in the treatment-naïve group. There was no difference concerning the leakage area in both groups. No adverse events were reported. CONCLUSION: We concluded that micropulse 577nm laser therapy maintained the visual acuity and macular thickness at 3 months in both treatment-naïve and refractory DME.

Association Between First- and Third-Month Responses to Intravitreal Ranibizumab for Diabetic Macular Edema.

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).

Central Macular Thickness in a Healthy Mexican Population Using Huvitz Optical Coherence Tomography.

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<0.001) compared to females. There was no association between mean macular CST (r2=0.011; P=0.11) and age. Macular thickness was thicker in the inner ring than in the outer ring, and there were no significant differences in mean CST among age groups (P=0.70). CONCLUSION: Normal macular thickness values using the Huvitz OCT in a Mexican healthy population aged from 18-70 years were thinner in the foveal macular region than values reported in other populations. Female patients had a thinner CST, and age was not correlated with macular thickness.

Levosulpiride Increases the Levels of Prolactin and Antiangiogenic Vasoinhibin in the Vitreous of Patients with Proliferative Diabetic Retinopathy.

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.

Submacular Cysticercosis Successfully Treated through Conservative Management: Case Report.

Appropriate medical management can be an alternative in those patients with submacular cysticercosis in whom achieving good visual outcome with vitreoretinal surgery is not possible. We report the case of a 25-year-old female who presented complaining of blurred vision in her left eye associated with photopsias and metamorphopsias of 3 months duration. Initial visual acuity in the right eye was 20/20 and 20/100 in the left eye. Upon indirect ophthalmoscopy in the left eye, a yellow-white, dome-shaped, elevated lesion with foveal involvement was observed. The rest of the ophthalmological examination proved normal. With clinical findings and images, submacular cysticercosis was diagnosed, and vitreoretinal surgery was suggested. Nevertheless, the patient did not accept the treatment; therefore, medical management was initiated. Central nervous system involvement was ruled out, and treatment with praziquantel and systemic prednisolone was initiated. Cysticercosis was resolved with significant improvement of her symptoms and visual acuity.

Different approaches in the management of macular hemorrhage: Case reports and a literature review. / Diferentes abordajes en el manejo de las hemorragias maculares: reporte de casos y revisión de literatura.

INTRODUCTION: Macular hemorrhages result in a sudden and profound loss of vision. The primary treatment modalities include observation, intravitreal injection of antiangiogenic drugs, neodymium-doped yttrium aluminum garnet hialoidotomy, intravitreal injection of gas with or without tissue plasminogen activator, as monotherapy or combined with surgery. In this paper, we report four cases of macular hemorrhages of different causes treated with different approaches, and we review the literature in this regard. CASE PRESENTATION: All four patients presented different causes of macular hemorrhage. The first case had a preretinal hemorrhage due to a Valsalva retinopathy and was treated with surgery. Case 2 had a multilevel macular hemorrhage due to a rupture of a retinal arteriolar macroaneurysm and was treated with pneumatic displacement, laser, and intravitreal ranibizumab. Case 3 presented an extensive subretinal hemorrhage due to a choroidal rupture after high-energy ocular trauma that was also successfully treated with surgery. The last case was a preretinal hemorrhage due to diabetic retinopathy managed with neodymium-doped yttrium aluminum garnet laser. Different treatment approaches were successfully performed in all cases with good outcomes. CONCLUSION: There is an extensive range of options available for the management of macular hemorrhages, and the best option depends on the characteristics of each particular case. Proper and timely management of these diseases can achieve an excellent visual outcome, especially if the location of the hemorrhage is preretinal.

INTRODUCCIÓN: Las hemorragias maculares producen una pérdida de la visión súbita y profunda. Las principales modalidades de tratamiento incluyen observación, inyección intravítrea de fármacos antiangiogénicos, hialoidotomía con láser neodymium-doped yttrium aluminium garnet, inyección intravítrea de gas y/o activador de plasminógeno tisular, en monoterapia o combinadas con cirugía. En el presente trabajo reportamos cuatro casos de hemorragias maculares de distintas causas, tratadas con diferentes abordajes, y realizamos una revisión de la literatura al respecto. PRESENTACIÓN DE CASOS: Los cuatro pacientes mostrados presentaron diferentes causas de hemorragias maculares. El primer caso tuvo una hemorragia prerretiniana debido a retinopatía de Valsalva y fue tratado con cirugía, el Caso 2 tuvo una hemorragia macular multinivel debido a una rotura de un macroaneurisma arteriolar retiniano y fue manejado con desplazamiento neumático, láser y ranibizumab intravítreo, el Caso 3 presentó una hemorragia subretiniana extensa debido a rotura coroidea posterior a un trauma ocular cerrado de alta energía y fue tratado exitosamente con cirugía. El último caso presentó una hemorragia prerretiniana debido a retinopatía diabética, manejada con láser neodymium-doped yttrium aluminium garnet. Los diferentes tratamientos fueron realizados exitosamente con buenos resultados. CONCLUSIÓN: Existen amplias opciones disponibles para el manejo de las hemorragias maculares y la mejor opción depende de las características de cada caso en particular. El manejo apropiado y oportuno de éstas puede lograr un resultado visual bueno, especialmente si la localización de la hemorragia es prerretiniana.

The role of various imaging techniques in identifying and locating intraocular foreign bodies related to open-globe injury: three case reports and literature review. / Papel de distintas técnicas de imagen para identificar y localizar cuerpos extraños intraoculares relacionados con trauma ocular abierto: reporte de tres casos y revisión de la literatura.

BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSION: 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.

ANTECEDENTES: 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. PRESENTACIÓN DEL CASO: 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. CONCLUSIÓN: 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.

Diferentes abordajes en el manejo de las hemorragias maculares: reporte de casos y revisión de literatura / Different approaches in the management of macular hemorrhage: case reports and a literature review

INTRODUCCIÓN: Las hemorragias maculares producen una pérdida de la visión súbita y profunda. Las principales modalidades de tratamiento incluyen observación, inyección intravítrea de fármacos antiangiogénicos, hialoidotomía con láser neodymium-doped yttrium aluminium garnet, inyección intravítrea de gas y/o activador de plasminógeno tisular, en monoterapia o combinadas con cirugía. En el presente trabajo reportamos cuatro casos de hemorragias maculares de distintas causas, tratadas con diferentes abordajes, y realizamos una revisión de la literatura al respecto. PRESENTACIÓN DE CASOS: Los cuatro pacientes mostrados presentaron diferentes causas de hemorragias maculares. El primer caso tuvo una hemorragia prerretiniana debido a retinopatía de Valsalva y fue tratado con cirugía, el Caso 2 tuvo una hemorragia macular multinivel debido a una rotura de un macroaneurisma arteriolar retiniano y fue manejado con desplazamiento neumático, láser y ranibizumab intravítreo, el Caso 3 presentó una hemorragia subretiniana extensa debido a rotura coroidea posterior a un trauma ocular cerrado de alta energía y fue tratado exitosamente con cirugía. El último caso presentó una hemorragia prerretiniana debido a retinopatía diabética, manejada con láser neodymium-doped yttrium aluminium garnet. Los diferentes tratamientos fueron realizados exitosamente con buenos resultados. CONCLUSIÓN: Existen amplias opciones disponibles para el manejo de las hemorragias maculares y la mejor opción depende de las características de cada caso en particular. El manejo apropiado y oportuno de éstas puede lograr un resultado visual bueno, especialmente si la localización de la hemorragia es prerretiniana.

INTRODUCTION: Macular hemorrhages result in a sudden and profound loss of vision. The primary treatment modalities include observation, intravitreal injection of antiangiogenic drugs, neodymium-doped yttrium aluminum garnet hialoidotomy, intravitreal injection of gas with or without tissue plasminogen activator, as monotherapy or combined with surgery. In this paper, we report four cases of macular hemorrhages of different causes treated with different approaches, and we review the literature in this regard. CASE PRESENTATION: All four patients presented different causes of macular hemorrhage. The first case had a preretinal hemorrhage due to a Valsalva retinopathy and was treated with surgery. Case 2 had a multilevel macular hemorrhage due to a rupture of a retinal arteriolar macroaneurysm and was treated with pneumatic displacement, laser, and intravitreal ranibizumab. Case 3 presented an extensive subretinal hemorrhage due to a choroidal rupture after high-energy ocular trauma that was also successfully treated with surgery. The last case was a preretinal hemorrhage due to diabetic retinopathy managed with neodymium-doped yttrium aluminum garnet laser. Different treatment approaches were successfully performed in all cases with good outcomes. CONCLUSION: There is an extensive range of options available for the management of macular hemorrhages, and the best option depends on the characteristics of each particular case. Proper and timely management of these diseases can achieve an excellent visual outcome, especially if the location of the hemorrhage is preretinal.

Electric Shock Retinopathy: Case Report of a Late Retinal Manifestation.

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.

Papel de distintas técnicas de imagen para identificar y localizar cuerpos extraños intraoculares relacionados con trauma ocular abierto: reporte de tres casos y revisión de la literatura / The role of various imaging techniques in identifying and locating intraocular foreign bodies related to open-globe injury: three case reports and literature review

ANTECEDENTES 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. PRESENTACIÖN DEL CASO 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. CONCLUSIÓN 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: 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. CASE PRESENTATION: 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. CONCLUSION: 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.

Incidence of retinopathy of prematurity type 1 and type 2 in a regional Hospital of Social Security in the state of Queretaro, Mexico (2017-2018).

BACKGROUND: Retinopathy of prematurity (ROP), the primary cause of blindness in children, is a potential complication for 7.7% of live births in Mexico. Given that less than one-third of all neonatal intensive care units follow Mexican National ROP guidelines, there have been few reports regarding the incidences of types 1 and 2 ROP. METHODS: This was a retrospective study that investigated the incidence and onset of ROP in a representative sample of children in Mexico. We analyzed the results obtained by the ROP Detection and Treatment Program, compliant with the Mexican National ROP guidelines, over a 1-year period. This study included 132 children who were born prematurely, were initially screened between October 2, 2017 and October 1, 2018, and underwent follow-up based on their risk group (in accordance with the Mexican National ROP guidelines). RESULTS: The mean gestational age (GA) at birth was 32 weeks and 3 days (32w3d) (95% CI, ± 3 days), and the mean birth weight (BW) was 1594 g (95% CI, ± 96 g). The clinical features were as follows: 36.4% had immature retina without ROP, 22.0% had mild ROP, 5.3% had type 2 ROP, 27.3% had type 1 ROP, and 1.5% had advanced disease. Premature children with ROP requiring treatment (i.e., type 1 ROP + advanced ROP) were born at an MGA of 30w4d (95% CI, ± 5d; range, 26-35 weeks); their MBW was 1316 g (95% CI, ± 110 g; range, 830-2220 g). Diagnosis of ROP requiring treatment was made at a mean postmenstrual age (PMA) of 37w3d (95% CI, ± 5d; range, 31w1d to 42w1d). CONCLUSION: In Mexico, screening and close ophthalmological follow-up of children who present with risk factors of birth weight < 1750 g and gestational age ≤ 34 weeks, both of which are observed more frequently in children with type 1 ROP, appears essential for implementing timely treatments (within 72 h). This is particularly important for children with PMA between 36 and 38 weeks, which is considered to be the peak age for disease stages that require timely intervention.

Basis and Design of a Randomized Clinical Trial to Evaluate the Effect of Levosulpiride on Retinal Alterations in Patients With Diabetic Retinopathy and Diabetic Macular Edema.

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.

Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes.

Importance: A deep learning system (DLS) is a machine learning technology with potential for screening diabetic retinopathy and related eye diseases. Objective: To evaluate the performance of a DLS in detecting referable diabetic retinopathy, vision-threatening diabetic retinopathy, possible glaucoma, and age-related macular degeneration (AMD) in community and clinic-based multiethnic populations with diabetes. Design, Setting, and Participants: Diagnostic performance of a DLS for diabetic retinopathy and related eye diseases was evaluated using 494 661 retinal images. A DLS was trained for detecting diabetic retinopathy (using 76 370 images), possible glaucoma (125 189 images), and AMD (72 610 images), and performance of DLS was evaluated for detecting diabetic retinopathy (using 112 648 images), possible glaucoma (71 896 images), and AMD (35 948 images). Training of the DLS was completed in May 2016, and validation of the DLS was completed in May 2017 for detection of referable diabetic retinopathy (moderate nonproliferative diabetic retinopathy or worse) and vision-threatening diabetic retinopathy (severe nonproliferative diabetic retinopathy or worse) using a primary validation data set in the Singapore National Diabetic Retinopathy Screening Program and 10 multiethnic cohorts with diabetes. Exposures: Use of a deep learning system. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity of the DLS with professional graders (retinal specialists, general ophthalmologists, trained graders, or optometrists) as the reference standard. Results: In the primary validation dataset (n = 14 880 patients; 71 896 images; mean [SD] age, 60.2 [2.2] years; 54.6% men), the prevalence of referable diabetic retinopathy was 3.0%; vision-threatening diabetic retinopathy, 0.6%; possible glaucoma, 0.1%; and AMD, 2.5%. The AUC of the DLS for referable diabetic retinopathy was 0.936 (95% CI, 0.925-0.943), sensitivity was 90.5% (95% CI, 87.3%-93.0%), and specificity was 91.6% (95% CI, 91.0%-92.2%). For vision-threatening diabetic retinopathy, AUC was 0.958 (95% CI, 0.956-0.961), sensitivity was 100% (95% CI, 94.1%-100.0%), and specificity was 91.1% (95% CI, 90.7%-91.4%). For possible glaucoma, AUC was 0.942 (95% CI, 0.929-0.954), sensitivity was 96.4% (95% CI, 81.7%-99.9%), and specificity was 87.2% (95% CI, 86.8%-87.5%). For AMD, AUC was 0.931 (95% CI, 0.928-0.935), sensitivity was 93.2% (95% CI, 91.1%-99.8%), and specificity was 88.7% (95% CI, 88.3%-89.0%). For referable diabetic retinopathy in the 10 additional datasets, AUC range was 0.889 to 0.983 (n = 40 752 images). Conclusions and Relevance: In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes.

From Bench to Bedside: Translating the Prolactin/Vasoinhibin Axis.

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.

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

BACKGROUND: The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. METHODS: Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. RESULTS: Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. CONCLUSIONS: Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.