Optic disc microvascularity in patients with intravitreal dexamethasone implantation for branch retinal vein occlusion.

PURPOSE: To compare changes in optic disc microvascular parameters before and after treatment of patients who received IVD for macular edema secondary to BRVO, using optical coherence tomography angiography (OCT-A). METHODS: Eighteen BRVO patients who received only IVD treatment and 20 healthy controls were retrospectively reviewed. Patients with moderate or severe IOP spikes (>6mmHg) after implantation were excluded from the study. Whole, peripapillary, inside disc capillary density and retinal nerve fiber layer thickness (RNFLT) were recorded at the 2nd and 6th months after implantation. RESULTS: Whole, peripapillary and inside disc capillary densities were significantly lower in BRVO patients before implantation than in the control group (P<0.001 for all comparisons). Despite a mild mean IOP increase after IVD, no significant change was observed in whole, peripapillary and inside disc capillary vascular densities in the 2nd and 6th months (P>0.05 for all comparisons). The mean RNFLT of BRVO patients before IVD was lower than the control group, but this difference was not statistically significant (110.1±12.3µm and 115.6±10.7µm, P=0.131). The mean RNFLT at the 2nd and 6th months did not show a statistically significant difference after implantation (P=0.239, P=0.459). CONCLUSIONS: OCT-A shows the decrease in whole, peripapillary and inside disc microvascular parameters in BRVO patients compared to healthy subjects. No significant change in optic nerve head microvascular parameters was observed in patients without moderate or severe IOP spikes after treatment with IVD.

Resuturing after penetrating keratoplasty without trauma: Indications and results.

PURPOSE: To determine the indications, frequency, influential factors and clinical outcomes of resuturing in an atraumatic setting after penetrating keratoplasty (PK). METHODS: Medical records of all patients who underwent resuturing in the absence of traumatic wound dehiscences after PK between January 1, 2007 and December 31, 2015 were reviewed. The cases were divided into 2 groups: patients with suture-related problems underwent mandatory resuturing (mandatory group), and patients with post-PK ectasia or a progressive increase in K values and surgically induced astigmatism underwent optional resuturing (Optional group). Patient demographics and surgical indications for PK, reasons for and frequency of resuturing, time between PK and resuturing, and clinical outcomes were evaluated. RESULTS: The frequency of resuturing was 9.03% (59 of 633), and the mean age was 39.15±17.80 years. The most common indication for PK was keratoconus (42.4%) and the interval between PK and resuturing ranged from 0.03 to 32 months. The underlying cause leading to resuturing was suture-related problems in 43 eyes (72.9%), development of ectasia or progressive steepening of the K values and surgically induced astigmatism in 16 eyes (27.1%). The mean visual acuity increased, the K value and astigmatism decreased significantly following resuturing in both the mandatory group and the Optional group (P≤0.2). The decrease in astigmatism and K values was more marked in the Optional group, as expected (P≤0.001). CONCLUSION: While resuturing is essential in order to obtain wound integrity in the setting of dehiscence, it is effective in terms of achieving higher visual acuities and lower astigmatism and K values in high astigmatism and post-PK ectasia cases.

Chitosan in viscosupplementation: in vivo effect on rabbit subchondral bone.

BACKGROUND: To investigate the effect of intra-articular injection of Chitosan (Cs) added to hyaluronic acid (HA) on subchondral bone during osteoarthritis (OA), microarchitectural parameters and mineral density were measured in a rabbit model of early OA. A novel hybrid hydrogel adding reacetylated Cs of fungal origin to HA was compared to high molecular weight HA commercial formulation. METHOD: Eighteen rabbits underwent unilateral anterior cruciate ligament transection (ACLT) and were divided into three groups (Saline-group, HA-group and Hybrid-group) depending on the intra-articular injection compound. Eight contralateral knees were used as non-operated controls (Contralateral-group). Micro-computed tomography was performed six weeks post-ACLT to study subchondral bone microarchitectural parameters and mineral density at an early stage of OA development. RESULTS: Cartilage thickness mean value was reduced only in Saline-group compared to Contralateral-group. When the Hybrid-group was compared to Saline-group, subchondral bone microarchitectural parameters (trabecular thickness and trabecular bone volume fraction) were significantly changed; subchondral bone plate and trabecular bone mineral densities (bone mineral density and tissue mineral density) were reduced. When the Hybrid-group was compared to HA-group, subchondral bone microarchitectural parameters (subchondral plate thickness and trabecular thickness) and trabecular bone mineral densities (bone mineral density and tissue mineral density) were significantly decreased. CONCLUSION: Conclusion: Compared to HA alone, the novel hybrid hydrogel, constituted of Cs added to HA, enhanced microarchitectural parameters and mineral density changes, leading to subchondral bone loss in a rabbit model of early experimental OA.

Meniscal biomechanical alterations in an ACLT rabbit model of early osteoarthritis.

OBJECTIVE: The purpose of this study was to analyze the early biomechanical alterations of menisci during the early stage of osteoarthritis (OA) development and to correlate them with the chemical composition and matrix alteration. A particular focus was paid to pathological changes in glycosaminoglycan (GAG) content and collagen fiber architecture. DESIGN: Menisci (n = 24) were removed from rabbits' knee joints 6 weeks following surgical anterior cruciate ligament transection (ACLT). Both the anterior and posterior regions of medial and lateral menisci were characterized using indentation tests, Raman microspectroscopy (RM), biphotonic confocal microscopy (BCM) and histology. RESULTS: Mechanical and matrix alterations occurred in both regions of medial and lateral menisci. A significant decrease in the mechanical properties was observed in OA menisci, with a mean reduced modulus from 2.3 to 1.1 MPa. Microstructural observations revealed less organized and less compact collagen bundles in operated menisci than in contralateral menisci, as well as a loss of fiber tension. GAG content was increased in OA menisci, especially in the damaged areas. Neither changes in the secondary structure of collagen nor mineralization were detected through RM at this stage of OA. CONCLUSION: ACLT led to a disorganization of the collagen framework at the early stage of OA development, which decreases the mechanical resistance of the menisci. GAG content increases in response to this degradation. All of these results demonstrate the strong correlation between matrix and mechanical alterations.

A novel biocompatible hyaluronic acid-chitosan hybrid hydrogel for osteoarthrosis therapy.

A conventional therapy for the treatment of osteoarthrosis is intra-articular injection of hyaluronic acid, which requires repeated, frequent injections. To extend the viscosupplementation effect of hyaluronic acid, we propose to associate it with another biopolymer in the form of a hybrid hydrogel. Chitosan was chosen because of its structural similarity to synovial glycosaminoglycans, its anti-inflammatory effects and its ability to promote cartilage growth. To avoid polyelectrolyte aggregation and obtain transparent, homogeneous gels, chitosan was reacetylated to a 50% degree, and different salts and formulation buffers were investigated. The biocompatibility of the hybrid gels was tested in vitro on human arthrosic synoviocytes, and in vivo assessments were made 1 week after subcutaneous injection in rats and 1 month after intra-articular injection in rabbits. Hyaluronic acid-chitosan polyelectrolyte complexes were prevented by cationic complexation of the negative charges of hyaluronic acid. The different salts tested were found to alter the viscosity and thermal degradation of the gels. Good biocompatibility was observed in rats, although the calcium-containing formulation induced calcium deposits after 1 week. The sodium chloride formulation was further tested in rabbits and did not show acute clinical signs of pain or inflammation. Hybrid HA-Cs hydrogels may be a valuable alternative viscosupplementation agent.

A novel oxido-viscosifying Hyaluronic Acid-antioxidant conjugate for osteoarthritis therapy: biocompatibility assessments.

To overcome the problem of fast degradation of Hyaluronic Acid (HA) in the treatment of osteoarthritis (OA), HA was protected against the oxidative stress generated by the pathology. Antioxidant conjugated HAs were synthesized and tested in vitro for their resistance in an oxidative environment mimicking OA. HA-4-aminoresorcinol (HA-4AR) displayed the interesting property of increasing in viscosity under oxidative conditions because of crosslinking induced by electron transfer. The novel HA polymer conjugate was shown to be biocompatible in vitro on fibroblast-like synoviocytes extracted from an arthritic patient. This HA conjugate was also assessed in vivo by intra-articular injection in healthy rabbits and was found to be comparable to the native polymer in terms of biocompatibility. This study suggests that HA-4AR is a promising candidate for a next generation viscosupplementation formulation.

Dioxygen-binding kinetics and thermodynamics of a series of dicopper(I) complexes with bis[2-(2-pyridyl)ethyl]amine tridendate chelators forming side-on peroxo-bridged dicopper(II) adducts.

Copper-dioxygen interactions are of interest due to their importance in biological systems as reversible O2- carriers, oxygenases, or oxidases and also because of their role in industrial and laboratory oxidation processes. Here we report on the kinetics (stopped-flow, -90 to 10 degrees C) of O2-binding to a series of dicopper(I) complexes, [Cu2(Nn)(MeCN)2]2+ (1Nn) (-(CH2)n- (n = 3-5) linked bis[(2-(2-pyridyl)ethyl]amine, PY2) and their close mononuclear analogue, [(MePY2)Cu(MeCN)]+ (3), which form mu-eta 2:eta 2-peroxodicopper(II) complexes [Cu2(Nn)-(O2)]2+ (2Nn) and [(MePY2)Cu]2(O2)]2+ (4), respectively. The overall kinetic mechanism involves initial reversible (k+,open/k-,open) formation of a nondetectable intermediate O2-adduct [Cu2(Nn)(O2)]2+ (open), suggested to be a CuI...CuII-O2- species, followed by its reversible closure (k+,closed/k-,closed) to form 2Nn. At higher temperatures (253 to 283 K), the first equilibrium lies far to the left and the observed rate law involves a simple reversible binding equilibrium process (kon,high = (k+,open/k-,open)(k+,closed)). From 213 to 233 K, the slow step in the oxygenation is the first reaction (kon,low = k+,open), and first-order behavior (in 1Nn and O2) is observed. For either temperature regime, the delta H++ for formation of 2Nn are low (delta H++ = -11 to 10 kJ/mol; kon,low = 1.1 x 10(3) to 4.1 x 10(3) M-1 s-1, kon,high = 2.2 x 10(3) to 2.8 x 10(4) M-1 s-1), reflecting the likely occurrence of preequilibria. The delta H degree ranges between -81 and -84 kJ mol-1 for the formation of 2Nn, and the corresponding equilibrium constant (K1) increases (3 x 10(8) to 5 x 10(10) M-1; 183 K) going from n = 3 to 5. Below 213 K, the half-life for formation of 2Nn increases with, rather than being independent of, the concentration of 1Nn, probably due to the oligomerization of 1Nn at these temperatures. The O2 reaction chemistry of 3 in CH2Cl2 is complicated, including the presence of induction periods, and could not be fully analyzed. However, qualitative comparisons show the expected slower intermolecular reaction of 3 with O2 compared to the intramolecular first-order reactions of 1Nn. Due to the likelihood of the partial dimerization of 3 in solution, the t1/2 for the formation of 4 remains constant with increasing complex concentration rather than decreasing. Acetonitrile significantly influences the kinetics of the O2 reactions with 1Nn and 3. For 1N4, the presence of MeCN inhibits the formation of a previously (Jung et al, J. Am. Chem. Soc. 1996, 118, 3763-3764) observed intermediate. Small amounts of added MeCN considerably slow the oxygenation rates of 3, inhibit its full formation to 4, and increase the length of the induction period. The results for 1Nn and their mononuclear analogue 3 are presented, and they are compared with each other as well as with other dinucleating dicopper(I) systems.

Reversible cleavage and formation of the dioxygen O-O bond within a dicopper complex.

A key step in dioxygen evolution during photosynthesis is the oxidative generation of the O-O bond from water by a manganese cluster consisting of M2(mu-O)2 units (where M is manganese). The reverse reaction, reductive cleavage of the dioxygen O-O bond, is performed at a variety of dicopper and di-iron active sites in enzymes that catalyze important organic oxidations. Both processes can be envisioned to involve the interconversion of dimetal-dioxygen adducts, M2(O2), and isomers having M2(mu-O)2 cores. The viability of this notion has been demonstrated by the identification of an equilibrium between synthetic complexes having [Cu2(mu-eta2:eta2-O2)]2+ and [Cu2(mu-O)2]2+ cores through kinetic, spectroscopic, and crystallographic studies.