Pseudomelanoma diagnosis in a tertiary ophthalmologic centre in Spain.

BACKGROUND: The purpose of this study was to determine the types and frequency of lesions that can be misdiagnosed as choroidal or ciliary body melanomas (posterior uveal tract melanoma [PUM]). METHODS: This is a retrospective, descriptive study examining data from patients referred to Hospital La Paz in Madrid with the diagnosis of possible PUM between January 2005 and March 2020. All patients referred for PUM were studied. In collaboration with an oncology-specialized ophthalmologic centre, each patient underwent a full ophthalmic examination, ultrasonography, and optical coherence tomography, with agreed clinical criteria used to differentiate melanomas from pseudomelanomas. RESULTS: In our cohort of 715 patients, 48.9% had pseudomelanomas. Thirty-five different conditions were misdiagnosed as melanomas. The 5 most common conditions were choroidal nevus (40.5%), peripheral exudative hemorrhagic chorioretinopathy (12%), choroidal hemangioma (10.5%), choroidal metastasis (8%), and age-related macular degeneration (4%). CONCLUSIONS: Altering the diagnosis and changing the treatment and prognosis for patients can be difficult for a referral centre. Herein we present the largest European cohort investigated and highlight the importance of identifying the correct diagnosis to prevent mistreatment and possible overtreatment. These misdiagnoses can have an emotional effect on patients and their families, which could be avoided with a correct diagnosis. We analyze the most common pseudomelanoma diagnoses to help physicians better diagnose patients in their care.

Effectiveness and safety of fluocinolone acetonide intravitreal implant in diabetic macular edema patients considered insufficiently responsive to available therapies (REACT): a prospective, non-randomized, and multicenter study.

OBJECTIVE: To assess the effectiveness and safety of the intravitreal fluocinolone-acetonide implant (FAc-i) in patients with chronic diabetic macular edema who did not sufficiently respond to other available therapies. METHODS: This was a multicenter, prospective, non-randomized, and phase-IV observational study conducted on patients with recurrent-DME who were insufficient responders to currently available therapies (REACT-Study). The primary end-point was the mean change in best-corrected-visual-acuity from baseline to month-24 values. RESULTS: Thirty-one eyes from 31 patients were included in the study. Mean age was 68.0 ± 7.7 years, and 10 (32.3%) were women. Study patients had received 5.3 ± 7.3 previous DME treatments before starting the study. In the overall study sample, BCVA improved from 56.1 ± 12.3 letters at baseline to 62.4 ± 17.0 letters at month-24 (p = 0.0510). The eyes with a baseline BCVA < 70 ETDRS letters had a significant improvement in BCVA from 53.2 ± 10.2 letters at baseline to 61.5 ± 17.9 letters at month-24 (p = 0.0165). In the overall study population, central-subfoveal-thickness (CST) was significantly reduced from 474.0 ± 135.1 µm at baseline to 333.4 ± 135.6 at month-24 (p < 0.0001). Similarly, macular-volume (MV) was significantly reduced from 10.7 ± 2.7 mm3 at baseline to 9.6 ± 2.9 mm3 (p = 0.0027) at month-24. Among the 31 study eyes, 19 (61.3%) required an additional treatment for DME. Throughout the study, 9 (29.0%) eyes required ocular hypotensive medication for controlling their intraocular-pressure and 5 (16.1%) eyes underwent cataract surgery. CONCLUSIONS: In DME eyes who did not sufficiently respond to previous therapies, the FAc-i was associated with an improvement in visual and anatomic outcomes. There were no unexpected adverse-events. TRIAL REGISTRATION NUMBER: EudraCT identifier: 2016-001680-37.

THREE-YEAR TREATMENT OUTCOMES OF AFLIBERCEPT VERSUS RANIBIZUMAB FOR DIABETIC MACULAR EDEMA: Data from the Fight Retinal Blindness! Registry.

PURPOSE: Compare the 3-year outcomes of ranibizumab versus aflibercept in eyes with diabetic macular edema in daily practice. METHODS: This was a retrospective analysis of naive diabetic macular edema eyes starting intravitreal injections of ranibizumab (0.5 mg) or aflibercept (2 mg) from January 1, 2013 to December 31, 2017 that were collected in the Fight Retinal Blindness! Registry. RESULTS: We identified 534 eyes (ranibizumab-267 and aflibercept-267) of 402 patients. The adjusted mean (95% confidence interval) visual acuity change of +1.3 (-0.1 to 4.2) letters in the ranibizumab group and +2.4 (-0.2 to 5.1) letters (P = 0.001) in the aflibercept group at 3 years was not clinically different. However, the adjusted mean CST change seemed to remain significantly different throughout the 3-year period with higher reductions in favor of aflibercept (-87.8 [-108.3 to -67.4] µm for ranibizumab vs. -114.4 [-134.4 to -94.3] for aflibercept; P < 0.01). When baseline visual impairment was moderate (visual acuity ≤68 Early Treatment Diabetic Retinopathy Study letters), we found a faster improvement in visual acuity in eyes treated with aflibercept up until 18 months of treatment than eyes treated with ranibizumab, which then stayed similar until 36 months of treatment, whereas there was no apparent difference when baseline visual impairment was mild (visual acuity ≥69 Early Treatment Diabetic Retinopathy Study letters). The rate of serious adverse events was low. CONCLUSION: Aflibercept and ranibizumab were both effective and safe for diabetic macular edema over 3 years.

Cyclophilins A and B oppositely regulate renal tubular epithelial cell phenotype.

Restoration of kidney tubular epithelium following sublethal injury sequentially involves partial epithelial-mesenchymal transition (pEMT), proliferation, and further redifferentiation into specialized tubule epithelial cells (TECs). Because the immunosuppressant cyclosporine-A produces pEMT in TECs and inhibits the peptidyl-prolyl isomerase (PPIase) activity of cyclophilin (Cyp) proteins, we hypothesized that cyclophilins could regulate TEC phenotype. Here we demonstrate that in cultured TECs, CypA silencing triggers loss of epithelial features and enhances transforming growth factor ß (TGFß)-induced EMT in association with upregulation of epithelial repressors Slug and Snail. This pro-epithelial action of CypA relies on its PPIase activity. By contrast, CypB emerges as an epithelial repressor, because CypB silencing promotes epithelial differentiation, prevents TGFß-induced EMT, and induces tubular structures in 3D cultures. In addition, in the kidneys of CypB knockout mice subjected to unilateral ureteral obstruction, inflammatory and pro-fibrotic events were attenuated. CypB silencing/knockout leads to Slug, but not Snail, downregulation. CypB support of Slug expression depends on its endoplasmic reticulum location, where it interacts with calreticulin, a calcium-buffering chaperone related to Slug expression. As CypB silencing reduces ionomycin-induced calcium release and Slug upregulation, we suggest that Slug expression may rely on CypB modulation of calreticulin-dependent calcium signaling. In conclusion, this work uncovers new roles for CypA and CypB in modulating TEC plasticity and identifies CypB as a druggable target potentially relevant in promoting kidney repair.

Use of OCT Angiography in Choroidal Melanocytic Tumors.

OBJECTIVE: To describe OCTA findings in choroidal melanocytic tumors, especially the microcirculation patterns, and to try to correlate with the histopathological studies. METHODS: Cross-sectional, comparative, observational study. 70 cases, including 55 choroidal nevi and 15 choroidal melanomas. Three different observers evaluated specific variables in the choriocapillaris layer on AOCT images and searched for images which described histopathologic vascular patterns, and also, a general description of the images was made. Complementary multi-imaging studies included EDI SD-OCT, color and autofluorescence fundus imaging, Doppler ultrasound, and indocyanine/fluorescein angiography. MAIN RESULTS: Good quality studies were acquired in 80% of the cases, with kappa indexes 0.768-0.958. Nevus OCTA images were described mainly as hyperreflective (72.7%), whereas choroidal melanoma as iso/hyporeflective (62.5%). Avascular areas were found in 50.96% and in 33.3% of choroidal nevus and choroidal melanomas, respectively. A neovascular membrane was found only in cases of choroidal nevus (16.3%). Only in cases of choroidal melanomas, we found vascular loops (6.6%) or vascular networks (6.6%). CONCLUSION: OCTA is a promising new technology that can be used to study in vivo the differential characteristics of microcirculations between posterior segment melanocytic lesions. Today, larger studies are needed to corroborate these findings and to correlate it with malignancy.

Sustentabilidad y variabilidad climática: acciones agroecológicas participativas de adaptación y resiliencia socioecológica en la región alto-andina colombiana / Sustentability and climate variability: participatory agroecologycal actions to adaptation and socio-ecological reesilience in the colombian high- andean region

La variabilidad climática constituye en la actualidad uno de los principales factores de riesgo para la agricultura y la seguridad alimentaria mundial. Los ecosistemas más vulnerables en Colombia son los que se ubican en la zona alto-andina donde miles de familias campesinas se dedican a la agricultura en pequeña escala. Los programas enfocados a adaptar la agricultura a la variabilidad climática no se apoyan suficientemente en el conocimiento local ni motivan a las comunidades para la acción. Esta investigación propuso un análisis de la relación entre sustentabilidad y adaptación a la variabilidad climática, reconociendo de manera participativa los principales factores de riesgo para la sustentabilidad de la agricultura a partir de indicadores y analizando la efectividad de planes de mejora en la capacidad adaptativa de la agricultura alto-andina. Se desarrolló como un estudio de caso con 13 productores familiares vinculados a la Asociación Red Agroecológica Campesina de Subachoque, en 3 fases: a) creación de un marco de análisis sobre los principales factores de riesgo para la agricultura; b) evaluación de la sustentabilidad a partir de indicadores propios y c) implementación de planes para aumentar la capacidad adaptativa de la agricultura. La evaluación realizada en dos momentos diferentes demostró mejora en los 9 indicadores generados, de forma que la implementación de las acciones para mejorar la sustentabilidad influyeron positivamente sobre la capacidad de las fincas para adaptarse a los riesgos de la variabilidad climática. Las estrategias agroecológicas implementadas mejoraron la resiliencia socioecológica de los agroecosistemas manejados por agricultores familiares, aumentando la posibilidad de que respondan mejor ante cualquier escenario de cambio ambiental.

Climate variability constitutes actually one of the main risks to agriculture and food security in the world. The most vulnerable ecosystems in Colombia are located in the high region of the Andeans where thousands of families farming lives from agriculture in small scale. The programs aimed to adapt the agriculture to climate variability do not take into account the local knowledge; neither motivates communities to action. This research proposed an analysis of the relationship between sustainability and agricultural adaptation to climate variability in a participatory way, recognizing the main risk factors to agriculture sustainability using indicators and analyzing the effectiveness of improving plans to the agricultural adaptation capacity in the high-Andeans. It was developed as a study case with 13 farmers linked to the Agro-ecological Farming Net Association of Subachoque. 3 phases were developed: a) the creation of a framework regarding the main the risks factors to the agriculture; b) sustainability appraisal based on own indicators and c) implementation of plans to increase the agricultural adaptation capacity. The appraisal developed in 2 different moments showed improving in the 9 indicators suggesting that the implementation of actions to the sustainability of farming positively influenced on the farms capacity to face the risks of the climate variability. The agro-ecological strategies implemented, improving the socio-ecological resilience of agro-ecosystems managed by family farmers, increasing the possibility that they better responding to any scenario of environmental change.

Vitreous diagnosis in neoplastic diseases.

Vitreous body is an intraocular structure, origin of diverse pathologies, but is also the place where cells and inflammatory mediators are released coming from several pathologic processes. These inflammatory reactions can happen in any other ocular location like choroid, retina, optic nerve, or ciliary body and vitreous humor constitutes a stagnant reservoir for these resulting substances and debris. Through the recent techniques of vitreous collecting, handling, and analysis, increasingly more sophisticated and with fewer complications, cellularity and molecules in the vitreous of challenging pathologies for the ophthalmologist can now be studied. The most usefulness for vitreous diagnosis would be the masquerade syndromes, and the best exponent in this group is the primary vitreoretinal lymphoma (PVRL), in which cytology and an IL-10/IL-6 ratio more than 1 is fundamental for the diagnosis.

Atypical clinical presentation and long-term survival in a patient with optic nerve medulloepithelioma: a case report.

INTRODUCTION: Medulloepithelioma is a rare congenital tumor of the primitive medullary neuroepithelium. A significant proportion of patients with medulloepithelioma arising from the optic nerve die from intracranial spread or cerebral metastasis. Because it has no known distinct clinical features and because of its low frequency, this tumor presents within the first two to six years of life and is usually misdiagnosed clinically as a different type of optic nerve tumor. Here, we describe a new and atypical case of medulloepithelioma of the optic nerve in a 12-year-old boy. To the best of our knowledge, he is the oldest reported patient to present with this disease and, now as an adult, has the longest documented period of disease-free survival. CASE PRESENTATION: A 12-year-old Caucasian boy with headache and unilateral amaurosis was referred for a presumed optic nerve glioma to our hospital. A computed tomography scan showed optic nerve enlargement, and fundoscopy showed a whitish mass at the optic disc. Our patient had been followed at his local hospital for four years for an 'optic disc cyst' with no change or progression. He experienced mild progressive visual impairment during that period. He was admitted for resection, and a histopathological analysis revealed a medulloepithelioma of the optic nerve. Supplemental orbital radiotherapy was performed. He remained disease-free for 25 years. CONCLUSIONS: Medulloepithelioma of the optic nerve can clinically mimic more common pediatric tumors, such as optic glioma, meningioma, or retinoblastoma. Thus, medulloepithelioma should be included in the differential diagnoses of pediatric optic nerve lesions. Fundoscopy in these patients may provide relevant information for diagnosis. Anterior optic nerve medulloepitheliomas may behave differently from and have a better prognosis than medulloepitheliomas that have a more posterior location. Our case report illustrates that long-term survival can be achieved in patients with this malignant tumor.

CD40 agonist antibody mediated improvement of chronic Cryptosporidium infection in patients with X-linked hyper IgM syndrome.

X-linked hyper-IgM syndrome (XHM) is a combined immune deficiency disorder caused by mutations in CD40 ligand. We tested CP-870,893, a human CD40 agonist monoclonal antibody, in the treatment of two XHM patients with biliary Cryptosporidiosis. CP-870,893 activated B cells and APCs in vitro, restoring class switch recombination in XHM B cells and inducing cytokine secretion by monocytes. CP-870,893 infusions were well tolerated and showed significant activity in vivo, decreasing leukocyte concentration in peripheral blood. Although specific antibody responses were lacking, frequent dosing in one subject primed T cells to secrete IFN-g and suppressed oocyst shedding in the stool. Nevertheless, relapse occurred after discontinuation of therapy. The CD40 receptor was rapidly internalized following binding with CP-870,893, potentially explaining the limited capacity of CP-870,893 to mediate immune reconstitution. This study demonstrates that CP-870,893 suppressed oocysts shedding in XHM patients with biliary cryptosporidiosis. The continued study of CD40 agonists in XHM is warranted.

Optic neuropathy following orbital irradiation for Graves' ophthalmopathy: a case report and literature review.

Radiation optic neuropathy (RON) is a devastating complication of radiotherapy to the anterior visual pathway resulting in acute, profound and sometimes irreversible visual loss. Cumulative doses of radiation that exceed 50 Gy or radiation fractions of greater than 2 Gy are usually required for RON to develop. Several factors, such as diabetes and pre-existing compression of the optic nerve, are associated with a higher risk for developing RON at lower doses of radiation. We report a case of presumed subacute RON following orbital irradiation for Graves' ophthalmopathy, successfully treated with megadoses of intravenous corticosteroids.

Emotional responses and attitudes to the peace talks with ETA / Respuestas emocionales y actitudes hacia las conversaciones de paz con ETA

In this study, two questions are analyzed: (1) what the emotions provoked by the Spanish government's declaration of its intention to negotiate a peace process with the terrorist group ETA are; (2) how these emotions relate to different attitudes to this negotiation. A questionnaire was applied to a sample of 263 university students. A confirmatory factor analysis was conducted to verify how emotions were organized and an ANOVA was subsequently conducted to analyze the relationship between emotions and attitudes to negotiation. With respect to the first question, the emotions which are linked to the negotiation process are classified in a three factor model (enthusiasm, anger and anxiety), and with respect to the second, it became clear that the emotion of anger is associated with subjects who are against negotiation. At the same time, enthusiasm and anxiety were associated with different attitudes to negotiation, support and rejection respectively; however, both these emotions were also found to be present among those who wanted the different political parties to reach an agreement and face the process of negotiation with a common policy.

En este estudio se analizan dos cuestiones: (1) cuáles son las emociones provocadas por la declaración del gobierno español ante su intención de negociar un proceso de paz con el grupo terrorista ETA; (2) cómo dichas emociones se relacionan con distintas actitudes hacia esa negociación. Se aplicó un cuestionario a una muestra de 263 estudiantes universitarios. Se realizó un análisis factorial confirmatorio con el fin de verificar cómo se organizaban las emociones y posteriormente se hizo un ANOVA para analizar la relación entre las emociones y las actitudes hacia la negociación. Con respecto a la primera cuestión, las emociones que se vinculan al proceso de negociación se clasifican dentro de un modelo con tres factores (entusiasmo, ira y ansiedad), y con respecto a la segunda, se observó que la emoción de ira está asociada a las personas que están en contra de la negociación. Al mismo tiempo, el entusiasmo y la ansiedad se asociaron con distintas actitudes respecto a la negociación, de apoyo y de rechazo, respectivamente; sin embargo, también se encontró que ambas emociones estaban presentes en las personas que querían que los distintos partidos políticos alcanzaran un acuerdo e hicieran frente al proceso de negociación con una política común.