Circulating MicroRNAs as Biomarker for Vessel-Associated Retinal Diseases.

INTRODUCTION: Vessel-associated retinal diseases are a major cause of blindness and severe visual impairment. The identification of appropriate biomarkers is of great importance to better anticipate disease progression and establish more targeted treatment options. MicroRNAs (miRNAs) are short, single-stranded, noncoding ribonucleic acids that are involved in the posttranscriptional regulation of gene expression through hybridization with messenger RNA. The expression of certain miRNAs can be different in patients with pathological processes and can be used for the detection and differentiation of various diseases. In this study, we investigate to what extent previously in vitro identified miRNAs are present as cell-free circulating miRNAs in the serum and vitreous of human patients with and without vessel-associated retinal diseases. METHODS: Relative quantification by quantitative real-time polymerase chain reaction was used to analyze miRNA expression in patients with vessel-associated retinal diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion compared with control patients. RESULTS: In serum samples, miR-29a-3p and miR-192-5p showed increased expression in patients with neovascular AMD relative to control patients. Similarly, miR-335-5p, miR-192-5p, and miR-194-5p showed increased expression in serum from patients with proliferative DR. In vitreous samples, miR-100-5p was decreased in patients with proliferative DR. Differentially expressed miRNAs showed good diagnostic accuracy in receiver operating characteristic (ROC) and area under the ROC curve analysis. CONCLUSION: The miRNAs investigated in this study may have the potential to serve as biomarkers for vessel-associated retinal diseases. Combining multiple miRNAs may enhance the predictive power of the analysis.

Short-Time Ocular Ischemia Induces Vascular Endothelial Dysfunction and Ganglion Cell Loss in the Pig Retina.

Visual impairment and blindness are often caused by retinal ischemia-reperfusion (I/R) injury. We aimed to characterize a new model of I/R in pigs, in which the intraocular pathways were not manipulated by invasive methods on the ocular system. After 12 min of ischemia followed by 20 h of reperfusion, reactivity of retinal arterioles was measured in vitro by video microscopy. Dihydroethidium (DHE) staining, qPCR, immunohistochemistry, quantification of neurons in the retinal ganglion cell layer, and histological examination was performed. Retinal arterioles of I/R-treated pigs displayed marked attenuation in response to the endothelium-dependent vasodilator, bradykinin, compared to sham-treated pigs. DHE staining intensity and messenger RNA levels for HIF-1α, VEGF-A, NOX2, and iNOS were elevated in retinal arterioles following I/R. Immunoreactivity to HIF-1α, VEGF-A, NOX2, and iNOS was enhanced in retinal arteriole endothelium after I/R. Moreover, I/R evoked a substantial decrease in Brn3a-positive retinal ganglion cells and noticeable retinal thickening. In conclusion, the results of the present study demonstrate that short-time ocular ischemia impairs endothelial function and integrity of retinal blood vessels and induces structural changes in the retina. HIF-1α, VEGF-A, iNOS, and NOX2-derived reactive oxygen species appear to be involved in the pathophysiology.

Binostril versus mononostril approaches in endoscopic transsphenoidal pituitary surgery: clinical evaluation and cadaver study.

OBJECTIVE Over the past 2 decades, endoscopy has become an integral part of the surgical repertoire for skull base procedures. The present clinical evaluation and cadaver study compare binostril and mononostril endoscopic transnasal approaches and the surgical techniques involved. METHODS Forty patients with pituitary adenomas were treated with either binostril or mononostril endoscopic surgery. Neurosurgical, endocrinological, ophthalmological, and neuroradiological examinations were performed. Ten cadaver specimens were prepared, and surgical aspects of the preparation and neuroradiological examination were documented. RESULTS In the clinical evaluation, 0° optics were optimal in the nasal and sphenoidal phase of surgery for both techniques. For detection of tumor remnants, 30° optics were superior. The binostril approach was significantly more time consuming than the mononostril technique. The nasal retractor limited maneuverability of instruments during mononostril approaches in 5 of 20 patients. Endocrinological pituitary function, control of excessive hormone secretion, ophthalmological outcome, residual tumor, and rates of adverse events, such as CSF leaks and diabetes insipidus, were similar in both groups. In the cadaver study, there was no significant difference in the time required for dissection via the binostril or mononostril technique. The panoramic view was superior in the binostril group; this was due to the possibility of wider opening of the sella in the craniocaudal and horizontal directions, but the need for removal of more of the nasal septum was disadvantageous. CONCLUSIONS Because of maneuverability of instruments and a wider view in the sphenoid sinus, the binostril technique is superior for resection of large tumors with parasellar and suprasellar expansion and tumors requiring extended approaches. The mononostril technique is preferable for tumors with limited extension in the intra- and suprasellar area.

Use of a clinicoradiological score to determine the presurgical diagnosis of autoimmune hypophysitis in a teenage girl.

The distinction between autoimmune hypophysitis and other non-hormone secreting pituitary masses is often difficult to determine with certainty without pituitary biopsy and pathological examination. To aid in this distinction, the authors recently published a clinicoradiological scoring system, which they used in the case of a 15-year-old girl presented here. The patient presented with headache, visual field defects, polydipsia, and polyuria, and she was found to have secondary hypogonadism and hypoadrenalism. Magnetic resonance imaging showed a pituitary mass of approximately 2 cm in diameter. Application of the clinicoradiological parameters gave a score of -6, which favored a diagnosis of hypophysitis over that of adenoma. The presence of pituitary autoantibodies substantiated the diagnosis of hypophysitis. The patient was treated conservatively with high-dose prednisolone, and her symptoms improved markedly. This case illustrates the utility of using a clinicoradiological score when autoimmune hypophysitis is suspected since it can identify patients who can be treated without the need for pituitary surgery.

Primary treatment of acromegaly with high-dose lanreotide: a case series.

INTRODUCTION: The first-line treatment for acromegaly is transsphenoidal surgery. In approximately 50% of patients, however, a cure is not possible with surgery and alternatives are needed. Somatostatin analog therapy is the recommended first-line treatment in patients with such cases. Here we provide the first report of a high-dose lanreotide primary therapy in patients with acromegaly. CASE PRESENTATION: Six patients who were not suitable for surgery were given 60 mg of lanreotide (Autogel(R)) every four weeks. All patients were German nationals and Caucasian.When the response of our patients was unsatisfactory, the dose was increased sequentially to 90 mg every four weeks, 120 mg every four weeks, 120 mg every three weeks and 180 mg every three weeks. Treatment duration was 12 to 24 months. In all cases, the lanreotide dose was 120 mg every 4 weeks or higher. In five of our patients, growth hormone (GH) levels were successfully reduced (in three patients GH <2.5 ng/ml was achieved). Insulin-like growth factor 1 levels were normalized in three patients and decreased in two patients. One patient failed to show a biochemical response to lanreotide therapy or pegvisomant therapy.Tumor shrinkage or degeneration was observed in the five responding patients. No drug-related adverse events were noted. CONCLUSIONS: These results suggest that lanreotide at high doses of 120 mg every four weeks or more is an effective first-line therapy for patients with acromegaly that surgery alone cannot treat.