Obostrana serozna korioretinopatija i pigmentni glaukom - koja je poveznica?

We present a patient with concurrent pigmentary glaucoma, bilateral central serous chorioretinopathy and unilateral optic disc pit, and propose a possible association of these conditions. Comprehensive ophthalmic examination of a 36-year-old man who was complaining of blurry vision and pain in the eyes showed reduced visual acuity on the left eye, elevated intraocular pressure in the right eye, bilateral signs of pigment dispersion syndrome, and bilateral central serous chorioretinopathy, combined with optic disc pit in the left eye. Visual field and optical coherence tomography findings demonstrated functional and structural glaucoma changes. Choroidal circulation abnormalities were observed by angiographic methods. Genetic and developmental anomalies of the external layer of the optic disc cup that gives rise to many anterior and posterior eye segment structures suggest a possible association of a clinical condition characterized by the combination of pigmentary glaucoma, central serous chorioretinopathy and optic disc pit. Future research would enable to determine proper diagnostic protocols, treatment and follow-up procedures for this chronic-progressive disorder.Prikazujemo slučaj bolesnika s pigmentnim glaukomom, obostranom centralnom seroznom korioretinopatijom i jednostranom jamicom optičkog diska te predlažemo moguću povezanost navedenih stanja. Sveobuhvatnim oftalmološkim pregledom 36-godišnjaka koji se žalio na zamagljen vid i bol u očima ustanovila se smanjena vidna oštrina lijevog oka, povišen očni tlak u desnom oku, obostrani znakovi sindroma disperzije pigmenta, obostrana centralna serozna korioretinopatija te jamica optičkog diska lijevo. Nalazi vidnog polja i optičke koherentne tomografije pokazali su glaukomske funkcionalne i strukturne promjene. Abnormalnosti koroidne cirkulacije uočene su angiografskim metodama. Genetske i razvojne anomalije vanjskog sloja čašice optičkog diska iz kojega se razvijaju strukture prednjeg i stražnjeg segmenta oka ukazuju na moguću vezu u kliničkom stanju koje obilježava kombinacija pigmentnog glaukoma, centralne serozne korioretinopatije i jamice optičkog diska. Buduća istraživanja bi omogućila utvrđivanje odgovarajućih dijagnostičkih postupaka, protokola liječenja i praćenja ovoga kronično-progresivnog stanja

Neinvazivno mjerenje pucanja suznog filma ručnim instrumentom za procjenu debljine lipidnog sloja suza

The aim was to determine feasibility and reliability of noninvasive tear break-up time (NIBUT) assessment using handheld lipid layer examination instrument, and to compare it with standard tear break-up time (TBUT) test. Fifty patients were enrolled, 31 with and 19 without dry eye symptoms. Schein questionnaire was used to assess dry eye symptoms. During examination, three NIBUT measurements were performed on each eye using handheld instrument, followed by three TBUT measurements. Receiver operating characteristic curves, sensitivity, specificity and logistic regression analysis were generated. Median NIBUT values were significantly shorter in dry eye symptom group than in control group in all three measurements (9, 8 and 8 s vs. 21, 22 and 21 s; p<0.001). TBUT values showed no significant difference between the groups in the first measurement (p=0.053), but the values were significantly shorter in dry eye symptom group in second and third measurements (p=0.020). The cutoff value to distinguish patients with symptoms of dry eye from control group was 12 seconds for NIBUT and 8 seconds for TBUT, with NIBUT having significantly higher sensitivity, specificity, area under the receiver operating characteristic curve and positive predictive value. NIBUT, measured by handheld lipid layer examination instrument, was superior to TBUT in detecting dry eye.Cilj ovoga istraživanja bio je ispitati pouzdanost mjerenja neinvazivnog testa pucanja suznog filma (NIBUT) pomoću ručnog instrumenta za procjenu debljine lipidnog sloja suza te ovu metodu usporediti sa standardnim invazivnim testom (TBUT). U istraživanje je bilo uključeno 50 ispitanika, 31 sa simptomima suhog oka i 19 bez njih. Za procjenu simptoma suhog oka rabio se standardni Scheinov upitnik. Za vrijeme pregleda provedena su tri mjerenja NIBUT-a pomoću ručnog instrumenta, potom tri mjerenja TBUT-a. Statističkom obradom podataka generirane su ROC krivulje, osjetljivost, specifičnost i regresijska analiza. Prosječna vrijednost NIBUT-a bila je značajno kraća u skupini bolesnika sa simptomima suhog oka nego u kontrolnoj skupini u sva tri mjerenja (9, 8, 8 s prema 21, 22, 21s; p<0.001). U prvom mjerenju se vrijednosti TBUT-a nisu značajno razlikovale među skupinama (p=0.053), no bile su značajno kraće u skupini sa simptomima suhog oka u drugom i trećem mjerenju (p=0.020). Granične vrijednosti testova NIBUT i TBUT bile su 12 i 8 sekunda, no NIBUT je imao bolju osjetljivost, specifičnost, područje ispod krivulje (AUC) te pozitivnu prediktivnu vrijednost. Metoda procjene NIBUT-a pomoću ručnog instrumenta za pregled debljine lipidnog sloja suza pokazala se boljom od testa TBUT u otkrivanju suhog oka

Iron overload in aging Bmp6−/− mice induces exocrine pancreatic injury and fibrosis due to acinar cell loss

The relationship between hemochromatosis and diabetes has been well established, as excessive iron deposition has been reported to result in impaired function of the endocrine and exocrine pancreas. Therefore, the objective of the present study was to analyze the effects of iron accumulation on the pancreata and glucose homeostasis in a bone morphogenetic protein 6‑knockout (Bmp6‑/‑) mouse model of hemochromatosis. The sera and pancreatic tissues of wild‑type (WT) and Bmp6‑/‑ mice (age, 3 and 10 months) were subjected to biochemical and histological analyses. In addition, 18F‑fluorodeoxyglucose biodistribution was evaluated in the liver, muscle, heart, kidney and adipose tissue of both animal groups. The results demonstrated that 3‑month‑old Bmp6‑/‑ mice exhibited iron accumulation preferentially in the exocrine pancreas, with no signs of pancreatic injury or fibrosis. No changes were observed in the glucose metabolism, as pancreatic islet diameter, insulin and glucagon secretion, blood glucose levels and glucose uptake in the liver, muscle and adipose tissue remained comparable with those in the WT mice. Aging Bmp6‑/‑ mice presented with progressive iron deposits in the exocrine pancreas, leading to pancreatic degeneration and injury that was characterized by acinar atrophy, fibrosis and the infiltration of inflammatory cells. However, the aging mice exhibited unaltered blood glucose levels and islet structure, normal insulin secretion and moderately increased α‑cell mass compared with those in the age‑matched WT mice. Additionally, iron overload and pancreatic damage were not observed in the aging WT mice. These results supported a pathogenic role of iron overload in aging Bmp6‑/‑ mice leading to iron‑induced exocrine pancreatic deficiency, whereas the endocrine pancreas retained normal function

Iron regulation mechanisms of bone morphogenetic protein pathway in tissue and plasma

Koštani morfogenetski protein 6 (BMP6) je ključni regulator hepcidina, proteina koji sudjeluje u održavanju homeostaze željeza. Istražili smo utjecaj željeza na BMP6 u tkivima i plazmi, te zašto ostale BMP molekule nisu u mogućnosti spriječiti hematokromatozu u Bmp6 -/- miševa. Kod miševa divljeg tipa, 4 sata nakon tretmana željezom dolazi do povećanja izražaja gena za BMP6 i hepcidin u jetri, dok je izražaj ostalih BMP molekula nepromijenjen. BMP6 je detektiran u cirkulaciji miševa i štakora, te je pružen prvi dokaz utjecaja željeza na povećanje razine BMP6 u plazmi. Naprotiv, u Bmp6 -/- miševa, tretman željezom dovodi do zakašnjele i slabije aktivacije Smad signalnog puta i sinteze hepcidina u jetri nakon 24 sata, zajedno s povećanim izražajem gena za BMP2, 4, 5 i 9 u duodenumu i BMP5 i BMP7 u jetri. Povećana sinteza BMP7 u jetri potencijalno doprinosi indukciji izražaja gena za hepcidin, što je dodatno podržano BMP7 terapijom koja dovodi do djelotvorne sinteze hepcidina i normalizacije serumskog željeza. No, sinteza BMP7 nije povezana s metabolizmom željeza, već s uzročnim oštećenjima jetre gdje BMP7 predstavlja mogući oblik obrambenog mehanizma od viška nakupljenog željeza. Rezultati pokazuju da akutna doza željeza aktivira kompenzacijske mehanizme s različitim BMP molekulama, ali nedovoljnog intenziteta da bi se spriječila hematokromatoza u Bmp6 -/- miševa. Učinkovita terapija s BMP7 sugerira da je BMP6 bitan, ali ne isključiv regulator homeostaze željeza in vivo.Bone morphogenetic protein 6 (BMP6) is a key regulator of hepcidin expression, a key iron regulatory hormone. We investigated the effect of iron on Bmp6 expression in tissues and plasma, and why other BMPs could not prevent hemochromatosis in Bmp6 -/- mice. In WT mice, 4 hours following iron challenge liver Bmp6 and Hamp expression were increased, while expression of other Bmps was not affected. In parallel, we provided the first evidence that iron increased the circulating BMP6 level. On the contrary, in Bmp6 -/- mice, iron challenge lead to a 24 hours delayed and blunted activation of liver Smad signaling and hepcidin expression, that was accompanied by an increased expression of Bmp2, 4, 5 and 9 in the duodenum and Bmp5 and Bmp7 in the liver. High liver Bmp7 expression potentially contributed to the late hepcidin response, which was further supported by BMP7 therapy resulting in an effective hepcidin expression and normalization of serum iron. However, BMP7 synthesis was not associated with iron metabolism, but the causal hepatic injuries where BMP7 represented a form of defense mechanism to the excessive iron accumulation. Our data indicate that iron activated BMP compensatory mechanisms that were not sufficient for preventing hemochromatosis in Bmp6 -/- mice. However, the effective BMP7 therapy suggested that BMP6 is an essential but not exclusive in vivo regulator of iron homeostasis

Muscle and Bone Defects in Metastatic Disease

Purpose of Review The present review addresses most recently identified mechanisms implicated in metastasis-induced bone resorption and muscle-wasting syndrome, known as cachexia. Recent Findings Metastatic disease in bone and soft tissues is often associated with skeletal muscle defects. Recent studies have identified a number of secreted molecules and extracellular vesicles that contribute to cancer cell growth and metastasis leading to bone destruction and muscle atrophy. In addition, alterations in muscle microenvironment including dysfunctions in hepatic and mitochondrial metabolism have been implicated in cancer-induced regeneration defect and muscle loss. Moreover, we review novel in vitro and animal models including promising new drug candidates for bone metastases and cancer cachexia. Preservation of bone health could be highly beneficial for maintaining muscle mass and function. Therefore, a better understanding of molecular pathways implicated in bone and muscle crosstalk in metastatic disease may provide new insights and identify new strategies to improve current anticancer therapeutics

Exogenous heparin binds and inhibits bone morphogenetic protein 6 biological activity

PURPOSE: The purpose of this study was to explore the effect of heparin on bone morphogenetic protein 6 (BMP6) osteogenic activity. ----- METHODS: Western blot analysis was used to confirm the binding of BMP6 to heparin and to observe its effect on BMP6 signaling in C2C12-BRE-Luc myoblasts. Real-time RT-PCR was performed for the expression analysis of alkaline phosphatase (ALP) and osteocalcin (OC) in C2C12 myoblasts treated with BMP6 and heparin for 72 hours. Rat ectopic bone formation assay was performed to explore the effect of heparin on BMP6 osteogenic activity. Two weeks following implantation the implants were analysed morphologically and histologically. A mouse osteoporotic model was used to test the ability of BMP6 to improve the bone quality in vivo in the presence of heparin, followed by DEXA and μCT analyses. Blood coagulation was tested in rats previously treated with BMP6. ----- RESULTS: BMP6 specifically bound to heparin and induced Smad1/5/8 phosphorylation which was inhibited by heparin. After 48 and 72 hours of treatment, heparin inhibited BMP6-induced ALP and OC expression in C2C12 cells. Heparin dose dependently inhibited BMP6-induced new bone and cartilage formation in the rat ectopic bone formation assay, while in osteoporotic mice heparin inhibited the BMP6 potential to improve the bone quality as evidenced by decreased bone mineral density and trabecular bone parameters. Interestingly, BMP6 prevented the effect of heparin on the blood coagulation parameters. ----- CONCLUSION: The interaction of BMP6 with heparin might contribute to the heparin-induced osteoporosis and blood coagulation

Meibomian Gland Assessment in Routine Ophthalmology Practice

This cross-sectional study aimed to investigate the connection between meibomian gland (MG) excreta quantity and quality after MG expression (MGX), dry eye disease (DED) symptoms, and objective DED signs and to clarify the relationship between dry eye and MG function in DED pathophysiology. The study included 200 subjects, 100 with and 100 without dry eye symptoms. Schein questionnaire was used to determine the severity of dry eye symptoms and self-reported skin type for facial skin dryness self-evaluation. Objective dry eye signs were assessed by monitoring conjunctival hyperemia, lid parallel conjunctival folds (LIPCOF), tear break-up time (TBUT), fluorescein surface staining and digital MGX. Subjects with DED symptoms had significantly lower MG quantity scores than healthy controls (p p = 0.002), Schein questionnaire score (p p = 0.019), self-reported skin type (p p p = 0.041). After adjustment for age and gender in a logistic regression analysis, dry eye was independently and significantly associated with self-reported skin type (OR 0.73, p p p = 0.019), TBUT (OR 0.77, p p < 0.001). Dry eye symptoms and objective signs correlated well in this study. MGX discriminated between the subjects with and without DED symptoms and was associated with other objective DED signs. Results showed a significant association between meibum quality and quantity, MG function, DED and facial skin dryness self-perception. This paper established a correlation between dry eye symptoms caused by MG dysfunction and dry skin, which can help general health practitioners consider dry eye as a cause of chronic eye complaints with patients who report dry skin

Bilateral juxtapapillary choroidal neovascularization secondary to Birdshot chorioretinopathy—case report

Central vision loss, photopsia, floaters, and macular edema in a highly myopic patient can easily be misinterpreted as high myopia complications. In atypical cases, detailed examination and a thorough diagnostic workup are required to establish the proper diagnosis, which is often beyond the scope of diagnoses initially considered

Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice

PURPOSE: Iron overload accelerates bone loss in mice lacking the bone morphogenetic protein 6 (Bmp6) gene, which is the key endogenous regulator of hepcidin, iron homeostasis gene. We investigated involvement of other BMPs in preventing haemochromatosis and subsequent osteopenia in Bmp6-/- mice. ----- METHODS: Iron-treated wild-type (WT) and Bmp6-/- mice were analysed for hepcidin messenger RNA (mRNA) and tissue and blood BMP levels by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), immunohistochemistry, Western blot, enzyme-linked immunosorbent assay (ELISA) and proximity extension assay. BMPs labeled with technetium-99m were used in pharmacokinetic studies. ----- RESULTS: In WT mice, 4 h following iron challenge, liver Bmp6 and hepcidin expression were increased, while expression of other Bmps was not affected. In parallel, we provided the first evidence that BMP6 circulates in WT mice and that iron increased the BMP6 serum level and the specific liver uptake of (99m)Tc-BMP6. In Bmp6-/- mice, iron challenge led to blunted activation of liver Smad signaling and hepcidin expression with a delay of 24 h, associated with increased Bmp5 and Bmp7 expression and increased Bmp2, 4, 5 and 9 expression in the duodenum. Liver Bmp7 expression and increased circulating BMP9 eventually contributed to the late hepcidin response. This was further supported by exogenous BMP7 therapy resulting in an effective hepcidin expression followed by a rapid normalisation of plasma iron values and restored osteopenia in Bmp6-/- mice. ----- CONCLUSION: In Bmp6-/- mice, iron activated endogenous compensatory mechanisms of other BMPs that were not sufficient for preventing hemochromatosis and bone loss. Administration of exogenous BMP7 was effective in correcting the plasma iron level and bone loss, indicating that BMP6 is an essential but not exclusive in vivo regulator of iron homeostasis

Tolerability in Glaucoma Patients Switched from Preserved to Preservative-Free Prostaglandin-Timolol Combination: A Prospective Real-Life Study

Purpose: To evaluate the effect of switching from preserved prostaglandin analog-timolol fixed combinations (PG-timolol FCs) to preservative-free latanoprost-timolol FC (PF-LT) on intraocular pressure (IOP), ocular surface health, and tolerability in glaucoma and ocular hypertension (OH) patients with the concurrent ocular surface disease (OSD). Methods: This was a longitudinal, prospective, interventional, real-life study among 42 patients. Up to 3 visits were planned, at baseline, 30, and 90 days to assess efficacy on IOP decrease and local tolerance. The severity of OSD symptoms [Ocular Surface Disease Index (OSDI) questionnaire], subjective drug tolerability [visual analog scale (VAS)], conjunctival hyperemia (McMonnies scale), and tear break-up time (TBUT) were the main parameters assessed. Results: Data from 36 patients were available for statistical analysis. IOP was significantly reduced at day 30 and day 90 compared to baseline (16 vs 14 vs 14 mmHg, p < 0.001). Significant improvement was demonstrated in OSD symptoms, signs, and VAS scores from the baseline to the second and third visits. Median OSDI (27.1 vs 9.6 vs 4.2, p < 0.001), conjunctival hyperemia (2 vs 1 vs 1, p < 0.001), corneal surface staining (p < 0.001), and conjunctival staining scores (p < 0.001), and the percentage of patients with eyelid and periocular hyperemia (61.1 vs 12.5 vs 2.8%, p < 0.001), significantly decreased. TBUT (4 vs 5 vs 6 s, p < 0.001) and VAS score regarding tolerability (5 vs 2 vs 1, p < 0.001) significantly increased. Conclusion: A switch from preserved PG-timolol FCs to PF-LT improved tolerability and optimized IOP control, providing better adherence with greater chances of treatment success