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There is no competing financial interest in this research. This research has not received external funding from public or private entities, nor do any of its authors have a personal financial interest in them or any family member or institutional affiliation. Furthermore, none of the authors has received grants or any forms of compensation (travel funding, consultancies, board position, patents, royalty arrangement, stock share or bonds). None of the authors has been nominated for relevant employment or received remuneration for being an expert witness or providing testimony about this ongoing research. The APC was funded by PAIDI Group RNM-279 "Geografia Fisica y Territorio"., Climate change generates negative impacts on human health. However, little is known about specific impacts on eye diseases, especially in arid and semi-arid areas where increases in air temperatures are expected. Therefore, the main goals of this research are: (i) to highlight the association between common eye diseases and environmental factors; and (ii) to analyze, through the available literature, the health expenditure involved in combating these diseases and the savings from mitigating the environmental factors that aggravate them. Mixed methods were used to assess the cross-variables (environmental factors, eye diseases, health costs). Considering Southern Spain as an example, our results showed that areas with similar climatic conditions could increase eye diseases due to a sustained increase in temperatures and torrential rains, among other factors. We highlight that an increase in eye diseases in Southern Spain is conditioned by the effects of climate change by up to 36.5%; the economic burden of the main eye diseases, extrapolated to the rest of the country, would represent an annual burden of 0.7% of Spain’s Gross Domestic Product. In conclusion, the increase in eye diseases has a strong economic and social impact that could be reduced with proper management of the effects of climate change. We propose a new concept: disease sink, defined as any climate change mitigation action which reduces the incidence or morbidity of disease., PAIDI Group RNM-279

Duchenne muscular dystrophy (DMD) is a fatal genetic disorder characterized by progressive muscle wasting that has currently no cure. Exon-skipping strategy represents one of the most promising therapeutic approaches that aim to restore expression of a shorter but functional dystrophin protein. The antisense field has remarkably progress over the last years with recent accelerated approval of the first antisense oligonucleotide-based therapy for DMD, Exondys 51, though the therapeutic benefit remains to be proved in patients. Despite clinical advances, the poor effective delivery to target all muscle remains the main hurdle for antisense drug therapy. This review describes the antisense-based exon-skipping approach for DMD, from proof-of-concept to first marketed drug. We discuss the main obstacles to achieve a successful exon-skipping therapy and the latest advances of the international community to develop more powerful chemistries and more sophisticated delivery systems in order to increase potency, bioavailability and safety. Finally, we highlight the importance of collaborative efforts and early dialogue between drug developers and regulatory agencies in order to overcome difficulties, find appropriate outcome markers and collect useful data.

ResumenPresentamos el caso de un ex toxicómano de 50 años que acudió a consulta de oftalmología con visión borrosa bilateral. En la anamnesis refería su desintoxicación 20 años atrás, con abstinencia total desde entonces y buena reinserción social. Su historia clínica reflejaba serología de hepatitis B+ y C+, pero VIH− y recientemente comenzó con esclerosis múltiple, controlada con interferón beta. Señalaba haber padecido últimamente un resfriado invernal prolongado.En la exploración oftalmológica se apreciaba una uveítis bilateral con precipitados queráticos. En funduscopia del ojo derecho destacaban múltiples granulomas coroideos y zonas de vasculitis periférica, activas y cicatriciales. La funduscopia del ojo izquierdo era normal.Tras diversas pruebas diagnósticas, como radiografía torácica y TAC pulmonar, se detectaron varios nódulos pulmonares. Asimismo, se realizó una prueba de Mantoux que resultó fuertemente positiva. La analítica mostraba neutropenia y linfopenia importantes. Por todo ello se hizo un diagnóstico de presunción de panuveítis secundaria a tuberculosis sistémica.Se administraron fármacos antituberculosos y corticoides sistémicos, con buena respuesta clínica sistémica y ocular.El interferón beta 1b es un inmunomodulador apropiado para la esclerosis múltiple, pero sus principales efectos secundarios son alteraciones analíticas como leucopenia, linfocitopenia y trombocitopenia.Los linfocitos CD4+ T, leucocitos, macrófagos y granulocitos, con la producción de sus mediadores interferón gamma, IL-12 o TNF-α son fundamentales para controlar al Mycobacterium tuberculosis. Por ello, antes de introducir Interferón beta 1b, convendría realizar técnicas de screening, como la prueba de Mantoux o el interferon gamma release assay–(quantiferon-TB) para detectar posibles tuberculosis latentes potencialmente activables.AbstractAn ex-drug addict 50 years-old man came to our hospital with bilateral blurred vision. The anamnesis revealed his detoxification 20 years ago, with complete drug abstinence since then and a good social reinsertion. His medical history showed a serology for Hepatitis B+ and C+ viruses, but it showed VIH−. Recently, he began to suffer multiple sclerosis disease, but it was well-controlled with interferon-beta. He also mentioned to have suffered a recent, prolonged winter cold.The ophthalmologic examination enables identification of bilateral uveitis with keratic precipitates. The right eye funduscopy revealed several choroidal granulomas, besides healed and actives peripheral vasculitis zones. The left eye funduscopy was normal.After several diagnostic tests as chest x-ray and pulmonary CAT scan, several pulmonary nodules were found. Also, it was carried out a Mantoux-test that was strongly positive. The blood analysis showed neutropenia and lymphopenia. Consequently, we proposed a presumptive diagnosis of panuveitis related to systemic tuberculosis.Anti-tuberculosis drugs and systemic corticoids were given, with a good clinical and ocular response.Interferon-beta 1b is a suitable immunomodulator for multiple sclerosis treatment, but its main secondary effects are blood abnormalities as leukopenia, lymphocytopenia and thrombocytopenia.CD4+ T lymphocytes, leukocytes, macrophages and granulocytes, furthermore the production of its mediators: interferon gamma, IL-12 or TNF-α, are essential to control Mycobacterium tuberculosis. Thus, before introduction of interferon-beta 1b, it would be advisable to attempt screening techniques, as Mantoux-test or interferon gamma release assay (quantiferon-TB) to detect probably latent tuberculosis, potentially likely to be active again.

ResumenLa retinosis pigmentaria unilateral es una patología relativamente infrecuente, no habiendo sido recogidos más de un centenar de casos en la bibliografía científica desde 1865. Por tanto, la asociación con foseta papilar es todavía más infrecuente, no quedando descartado un mecanismo intrínseco común.Presentamos el caso de una paciente de 66 años de edad, seguida desde el año 2000 en nuestro servicio, con una coincidencia de foseta papilar y retinosis pigmentaria unilateral en el mismo ojo. Como consecuencia de la foseta papilar desarrolló un proceso de desprendimiento seroso macular que no se reabsorbió espontáneamente y que acabó produciendo un agujero lamelar macular.Este tipo de complicaciones actualmente son en algunos casos tratadas con vitrectomía; sólo que la coincidencia en el mismo ojo de retinosis pigmentaria y foseta papilar hizo que se modificara la indicación terapéutica por la enorme degeneración y atrofia de la retina periférica de dicho ojo. Así, se optó finalmente por una fotocoagulación con láser de argón en el borde de la foseta papilar, consiguiendo una importante ganancia visual y evitando las variaciones visuales que a lo largo del día experimentaba la paciente, por haberse acumulado líquido en la mácula a lo largo de la noche, frenando el proceso de deterioro macular.AbstractUnilateral retinitis pigmentosa is a relatively rare disease: scientific research has not found more than one hundred cases since 1865. Therefore, this pathology in association with optic disc pit is increasingly rare; in this association it is possible to understand a common intrinsic mechanism.We show a 66-years-old woman monitored since 2000 by our service, with a unilateral retinitis pigmentosa and optic disc pit coincidence in the same eye. As a result of the optic disc pit she developed a serous macular detachment which was not naturally reabsorbed and which caused a lamellar macular hole.These complications are actually treated with vitrectomy in some cases; but the unilateral retinitis pigmentosa and optic disc pit coincidence in the same eye forced us to modify the therapeutic indication because of a wide degeneration and the atrophy of peripheral retina of that eye. Thus, we finally chose to apply argon laser photocoagulation in peripheral area of optic disc pit, achieving an important visual improvement and saving the patient from visual variation she used to suffer throughout the day because of a liquid accumulation in macula during the night. so her macular damage process stopped.