Backgroundvon Hippel-Lindau disease (VHL) is a multisystem cancer syndrome caused by mutations in the VHL gene. Retinal hemangioblastoma is one of the most common tumours, and when it appears near the optic nerve, its treatment is challenging and risky. To date, no treatment has proven effective in changing the course of the disease. This study was designed to evaluate the safety and effectiveness of propranolol in controlling these tumours.MethodsSeven patients were included. All patients took a daily dose of 120 mg of propranolol for 1 year. Clinical variables were assessed at baseline, and at 1, 3, 6, 9 and 12 months. The primary endpoint of the study was the number and size of retinal hemangioblastomas. On every visit, retinal outcomes and blood biomarkers (such as vascular endothelial growth factor (VEGF) and miR210) were analysed.ResultsNumber and size of retinal hemangioblastomas remained stable in all patients. All of them had initially increased levels of VEGF and miR210. There was a gradual reabsorption of retinal exudation in two patients, correlating with a progressive decrease of both biomarkers. The only adverse effect reported was hypotension in one patient.ConclusionsPropranolol could be used to treat retinal hemangioblastomas in VHL patients, although more studies are needed to determine the ideal dose and long-term effect. VEGF and miR210 should be explored as biomarkers of disease activity. As far as we know, these are the first biomarkers proposed to monitor the VHL disease activity.Trial registration number2014-003671-30

Progranulin (PGRN) is a glycoprotein formed by 593 amino acids encoded by the GRN gene. It has an important role in immunity and inflammatory response, as well as in tissue recovery. Its role in musculoskeletal inflammatory diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and intervertebral disc degeneration disease (IVDD), is, nowadays, an important target to investigate. The objective of this review is to systematically sum up all the recent findings concerning PGRN as a target in the development and resolution of the inflammatory diseases. PubMed was examined with the terms combinations (Progranulin) AND (Lupus Erythematosus, Systemic), (Progranulin) AND (Arthritis, Rheumatoid), and (Progranulin) AND (Intervertebral Disc Degeneration). PubMed was examined with the terms combinations (Atsttrin) AND (Lupus Erythematosus, Systemic), (Atsttrin) AND (Arthritis, Rheumatoid), and (Atsttrin) AND (Intervertebral Disc Degeneration). Moreover, research through Web of Science was performed searching the same items. The inclusion criteria were: studies whose main topic were progranulin, or atsttrin, with emphasis on the three selected diseases. On the other hand, the exclusion criteria were studies that only focused on diseases not related to RA, lupus or IVDD, in addition to the previous published literature reviews. Since few results were obtained, we did not filter by year. The records assessed for eligibility were 23, including all the studies with the information in state of art of progranulin and its capability to be a potential target or treatment for each one of the selected diseases. As these results are descriptive and not clinical trials, we did not perform risk of bias methods. Within these results, many studies have shown an anti-inflammatory activity of PGRN in RA. PGRN levels in serum and synovial fluids in RA patients were reported higher than controls. On the other hand, serum levels were directly correlated with SLE disease activity index, suggesting an important role of PGRN as a player in the progression of inflammatory diseases and a therapeutical approach for the recovery. This review has some limitations due to the small number of studies in this regard; therefore, we highlight the importance and the necessity of further investigation. No external funding was implicated in this systematical review.

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Purpose. von Hippel Lindau (VHL) disease is a familiar syndrome associated with benign and malignant tumors. These tumors appear in the retina, cerebellum, spinal cord, and kidney. Retinal hemangioblastomas are one of the earliest and most frequent manifestations of this entity, and they can lead to blindness at a young age. Propranolol could be a promising treatment for retinal hemangioblastomas in von Hippel Lindau disease. Methods. Prospective cohort study. Seven patients with VHL disease and ocular affection that had rejected conventional treatment were included. Prospective analysis of seven patients was performed. We evaluated them for three years, with a complete ophthalmic evaluation that included: visual acuity, intraocular pressure, an examination of the anterior segment of the eye, fundoscopy, retinography, and optical coherence tomography (OCT). Heart rate and blood pressure on each patient were also measured. During the follow-up evaluation, two patients discontinued the treatment with propranolol after the first year and rejected any further treatment for their ocular affection; the rest continued therapy for the three years. Results: Visual acuity and tumor areas remained stable in 4 patients. Increased and new retinal exudation area was found in the two patients that discontinued the treatment with oral propranolol. Conclusions: Oral propranolol has shown a role in the reabsorption of retinal exudates in patients with von Hippel Lindau affection. It could delay or stabilize the ocular disease, maintaining visual acuity, and avoiding further complications in these patients. It is a well-known and available drug, without so many secondary effects, that could also have a role in other ocular diseases that course with exudation.

Background. von Hippel Lindau (VHL) disease is a familial syndrome associated with benign and malignant tumours. These tumours appear in the retina, among other locations. The retinal hemangioblastomas are one of the earliest and most frequent manifestations of this entity, and they can lead to blindness at a young age. Propranolol could be a promising treatment for retinal hemangioblastomas in von Hippel Lindau disease Methods. Prospective cohort study of seven patients with VHL disease and ocular affection that had rejected conventional treatment, taking oral propranolol. We evaluated them for three years, with a complete ophthalmic evaluation that included: visual acuity, intraocular pressure, an examination of the anterior segment of the eye, fundoscopy, retinography, and optical coherence tomography (OCT). Heart rate and blood pressure were also measured. During the follow-up evaluation, two patients discontinued the treatment with propranolol after the first year and rejected any further treatment for their ocular affection; the rest continued therapy. Results. Visual acuity and tumour areas remained stable in 4 patients. Increased and new retinal exudation area was found in the two patients that discontinued the treatment with oral propranolol. Conclusions. Oral propranolol has shown a role in the reabsorption of retinal exudates in patients with VHL affection. It could delay or stabilise the ocular disease, maintaining visual acuity and avoiding further complications in these patients. It is a well-known and available drug, without so many secondary effects, that could also have a role in other ocular diseases that course with exudation. Trial registration. VHL-HOPE-2014-1. EudraCT Number: 2014-003671-30; Registered 22 September 2014 - https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-003671-30/ES