Effect of Branching Degree of Dendritic Polyglycerols on Plasma Protein Adsorption: Relationship between Hydration States and Surface Morphology.

This study focuses on dendritic glycerols and investigates the construction of biocompatible surfaces by understanding how differences in the branching of these molecules change the interactions with the biological components. The two molecules, polyglycerol dendrimer (PGD), which has a completely branched structure, and hyperbranched polyglycerol (HPG), which has an incompletely branched structure, are compared and the differences in branching are evaluated. It is shown that PGD has a little bit more intermediate water than HPG, which reflects the differences in the branching. The effect of surface state on the adsorption of the plasma proteins, human serum albumin (HSA), fibrinogen (Fib), and fibronectin (FN), is discussed by modifying a glass surface using these molecules with different hydration states. The adsorption of HSA decreases to several percent for HPG and 10% for PGD compared to unmodified substrate. Although the adsorption of Fib decreases to 5% for HPG, an increase to 150% is observed for PGD. Since this specific Fib adsorption observed only onto PGD is suppressed in the cases of a mixed solution of HSA and Fib or sequentially using HSA solution and then Fib solution, it is thought that the Vroman effect is suppressed on the PGD-modified surface. Furthermore, when AFM measurements are performed in PBS to understand the surface roughness, PGD is found to be more highly non-uniform. Because of this, the nanometer scale roughness that is significantly observed only on the PGD-modified surface is thought to have an effect on the characteristic adsorption properties of Fib. Thus, although both PGD and HPG with different branching have intermediate water, the proportion differs between PGD and HPG. Therefore, it is found that differences occur in the plasma protein adsorption mechanisms depending on the coordinates and density of hydroxyl groups within the molecules.

A comparative study of transscleral suture-fixated and scleral-fixated intraocular lens implantation.

PURPOSE: To compare short-term clinical outcomes between scleral-fixated and transscleral suture-fixated intraocular lens (IOL) implantation. SEETING: Hiroshima Prefectural Hospital, Japan. DESIGN: A retrospective, nonrandomized, comparative case series. METHODS: Eighty-nine eyes of 87 patients were included in this study; 45 eyes underwent transscleral suture-fixated IOL implantation (group 1), and 44 eyes underwent scleral-fixated IOL implantation (group 2) between February 2009 and June 2017 in the department of Ophthalmology, Hiroshima Prefectural Hospital, Japan. The postoperative best corrected visual acuity (BCVA), degree of astigmatism, IOL astigmatism (total astigmatism-corneal astigmatism), and refractive error were all measured at 1-week and 1-month intervals. RESULTS: The mean preoperative BCVA in logarithm of minimum angle of resolution (log MAR) was 0.39 ± 0.56 and 0.46 ± 0.51 in groups 1 and 2, respectively, and the mean postoperative BCVA was 0.25 ± 0.41 and 0.34 ± 0.49 at 1 month. The postoperative degree of astigmatism in group 2 was significantly less than that in group 1 at 1 week and 1 month (p = 0.0046 and p = 0.021, respectively). The postoperative IOL astigmatism in group 2 was significantly less than that in group 1 at 1 week (p = 0.021), while the refractive error between the two groups was not significantly different at 1 week or 1 month. CONCLUSIONS: Scleral-fixated IOL implantation has equivalent BCVA and refractive error outcomes as transscleral suture-fixated IOL implantation during the early postoperative period without serious complications. Scleral-fixated IOL implantation appears to provide more stable fixation than suture-fixated IOL implantation.

Down-regulation of semaphorin 3F in rat retinal ganglion cells in response to optic nerve crush.

Glaucoma is characterized by degeneration of optic nerve axons and death of retinal ganglion cells (RGCs). Nerve crush and axotomy of the optic nerve are studied as models of RGC death in glaucoma and of axon regeneration. The mechanisms underlying the response of RGCs to axonal injury remain unclear, however. We have now examined the effects of optic nerve crush on the expression of members of the semaphorin family of neuronal guidance proteins in the rat retina. The expression of semaphorin 3F (Sema3F) in the retina was down-regulated at both the mRNA and protein levels at 7 days after optic nerve injury, whereas that of Sema3A, Sema3B or Sema3C remained unaffected. Immunohistofluorescence analysis and laser capture microdissection followed by reverse transcription-polymerase chain reaction analysis revealed that this loss of Sema3F expression occurred in the RGC layer of the retina. Furthermore, antibody-mediated neutralization of secreted Sema3F in retinal organ culture resulted in down-regulation of neuron-specific ßIII-tubulin (Tuj-1 antigen), a marker of RGCs. Our results suggest that Sema3F may contribute to the regulation of RGC function or survival and therefore warrants further investigation as a potential mediator of neuroprotection. Copyright © 2016 John Wiley & Sons, Ltd.

Intraocular Pressure Outcomes and Risk Factors for Failure in the Collaborative Bleb-Related Infection Incidence and Treatment Study.

PURPOSE: To evaluate the efficacy and safety of trabeculectomy for patients with glaucoma who were enrolled in the Collaborative Bleb-related Infection Incidence and Treatment Study (CBIITS). DESIGN: Multicenter, prospective, cohort study. PARTICIPANTS: A total of 829 eyes in 829 patients with glaucoma who had undergone trabeculectomy alone or trabeculectomy combined with phacoemulsification at 34 clinical centers were examined in this study. MAIN OUTCOME MEASURES: Intraocular pressures (IOPs, in millimeters of mercury), risk factors for surgical failure, and surgical complications. METHODS: The enrollment period was 2 years, and follow-up was conducted every 6 months for up to 5 years. Outcomes were measured at 6-month intervals. Four levels of success were defined by achievement of the following IOP: (A) 4

Effect of intravitreal bevacizumab on iris vessels in neovascular glaucoma patients.

BACKGROUND: We aimed to investigate the effects of a single 1-mg injection of intravitreal bevacizumab on iris vessels in neovascular glaucoma (NVG) patients. METHODS: Twenty-two surgically resected irises from glaucoma patients were obtained during trabeculectomy. Eight were from patients with NVG who received a 1-mg injection of intravitreal bevacizumab (IVB) before glaucoma surgery, eight were from patients with primary open-angle glaucoma (POAG), and six were from patients with NVG who were not administered IVB. The collected iris specimens were compared after immunohistochemical staining with anti-CD34 monoclonal antibodies and anti-VEGF monoclonal antibody, and the percentage of CD34-positive and VEGF-positive regions in the total area of the specimens from the three groups was compared. RESULTS: The difference in the CD34-positive area between all groups was statistically significant (p = 0.0061, Kruskal-Wallis test). There was no significant difference in the CD34-positive area between the NVG with IVB group and the POAG group (p = 0.3017, Mann-Whitney U test with Bonferroni correction). The POAG group had significantly fewer CD34-positive regions than the NVG without IVB group (p = 0.0019, Mann-Whitney U test with Bonferroni correction). Many vessels remained in the iris stroma, and there was no significant difference in the CD34-positive area between the NVG with IVB and NVG without IVB groups (p = 0.0357, Mann-Whitney U test with Bonferroni correction). The ratio of the length of CD34 expression on the iris surface in the NVG without IVB group was significantly longer than that in the NVG with IVB group (p = 0.0002, Mann-Whitney U test). The difference in VEGF expression between all groups was statistically significant (p = 0.04, Kruskal-Wallis test). There was no significant difference between the NVG with IVB group and the NVG without IVB group (p = 0.7963 Mann-Whitney U test with Bonferroni correction). The frequency of hyphema and fibrin formation in the anterior chamber 1 day after surgery between the two NVG groups was not statistically significant. CONCLUSION: A single intravitreal dose of IVB at 1 mg/0.04 ml to eyes with rubeotic glaucoma reduced the neovascularization in the human iris surface, but could not eliminate completely neovascularization in iris stroma. This finding implies that the prevention of hyphema and fibrin formation based on the slit-lamp examination can not be predicted, even if neovascularization in iris surface seems to be eliminated by a single dose of IVB.

Effectiveness of trabeculectomy with mitomycin C for glaucomatous eyes with low intraocular pressure on treatment eye drops.

PURPOSE: To examine the efficacy and safety of current trabeculectomy with mitomycin C in Japan for glaucomatous eyes with low intraocular pressure (IOP). METHODS: Two hundred ninety-four eyes of 294 patients with IOP ≤21 mmHg before surgery were studied; all patients were participants in the Collaborative Bleb-related Infection Incidence and Treatment Study (CBIITS), a multicentre, prospective, cohort study conducted at 34 ophthalmological institutions throughout Japan. All eyes had an intraocular pressure ≤ 21 mmHg and had undergone trabeculectomy alone or phacotrabeculectomy. Two success criteria were used: Criterion A comprised 20% reduction of baseline IOP and Criterion B comprised 30% reduction of baseline IOP. The primary outcome was the success rate for each of these criteria. RESULTS: The qualified success rates were 87.3% for Criterion A and 42.0% for Criterion B at 5 years. Mean IOP was significantly reduced, from 16.7 ± 2.7 to 11.6 ± 4.0 mmHg at 5 years after trabeculectomy (p < 0.0001); the number of anti-glaucoma medications significantly decreased from 2.7 ± 1.1 to 1.0 ± 1.2 (p < 0.0001) at 5 years after the surgery. Three or more trabeculectomies, and needling were related to increased risk of failure. Incidences of postoperative hyphema, infection, shallow anterior chamber and bleb leakage were 2.4%, 2.4%, 2.0% and 3.4%, respectively. CONCLUSIONS: This study showed that trabeculectomy with mitomycin C is an effective procedure with few surgical complications for reducing IOP in patients, even if preoperative IOP was within the normal range.

Craniosynostosis in a patient with a de novo 15q15-q22 deletion.

Interstitial deletions involving the chromosomal band 15q15 are very rare. A total of five cases were previously reported. Here another case of a 15q15.2-q22.2 deletion is reported, presenting with severe craniosynostosis of coronary, metopic, and sagittal sutures. The chromosome 15 with the 17.7-Mb deletion was of the paternal origin. A critical region for craniosynostosis may be located at the 734-kb segment at 15q15.2. Interestingly, the entire FBN1 gene was deleted in this patient.

The signs of ocular-surface disorders after switching from latanoprost to tafluprost/timolol fixed combination: a prospective study.

PURPOSE: To evaluate the ocular-surface safety of a 0.001% benzalkonium chloride-containing tafluprost/timolol fixed combination (TTFC) in patients with primary open-angle glaucoma (POAG) or ocular hypertension who have inadequate intraocular pressure (IOP) control with latanoprost monotherapy. METHODS: This study is a multicenter, prospective, single-arm, open-label clinical study. Patients with POAG or ocular hypertension who have inadequate IOP control with latanoprost monotherapy were considered eligible. After providing informed consent, patients continued latanoprost monotherapy for 12 weeks, followed by a switch to TTFC. We evaluated the extent of ocular-surface damage using superficial punctate keratopathy (SPK) score, tear breakup time (TBUT), hyperemia score, IOP, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate at 0, 4, and 12 weeks after switching. RESULTS: A total of 68 patients were enrolled, of whom, 64 patients were included in the final analysis. No significant changes in SPK score, TBUT, or hyperemia score were observed at 4 and 12 weeks compared with week 0. IOP decreased significantly at 4 (13.9±2.5 mmHg) and 12 (14.1±2.5 mmHg) weeks, relative to week 0 (15.3±2.7 mmHg). No significant changes in either SBP or DBP were observed during the study, although patients' mean heart rate decreased significantly after switching to TTFC. Adverse drug reactions to TTFC occurred in seven patients including two incidences of asthma and one of arrhythmia, and no events were serious. CONCLUSION: The ocular-surface safety of TTFC is not significantly different to that of latanoprost. Furthermore, switching from latanoprost to TTFC in patients with insufficient IOP control has additive IOP-lowering effects. TTFC is an effective approach for patients receiving latanoprost monotherapy who require more intensive IOP reduction.

Persistent hypotony after trabeculectomy: incidence and associated factors in the Collaborative Bleb-Related Infection Incidence and Treatment Study.

PURPOSE: To investigate the incidence of and factors associated with persistent hypotony after trabeculectomy with mitomycin C in the Collaborative Bleb-Related Infection Incidence and Treatment Study (CBIITS), a 5-year prospective multicenter study. METHODS: A total of 955 eyes of 955 patients who underwent trabeculectomy with mitomycin C were studied. Surgical failure was defined as insufficient intraocular pressure (IOP) reduction (IOP > 21 mmHg or <20 % IOP reduction, or further glaucoma surgeries), loss of light perception, or persistent hypotony (IOP ≤ 5 mmHg persisting for >6 months). Factors associated with persistent hypotony in eyes with sufficient IOP reduction were determined by survival analysis and logistic regression analysis. RESULTS: The cumulative probabilities of surgical success and persistent hypotony at 5 years were 62.0 ± 1.7 % (±standard error) and 7.7 ± 0.9 %, respectively. In 685 eyes with sufficient IOP reduction, preoperative IOP (mmHg), limbus-based conjunctival flap, or choroidal detachment that occurred within 6 months of the surgery were significant risk factors for persistent hypotony [Cox proportional hazards regression model: hazard ratio, 0.95, 2.27, 3.24; 95 % confidence interval (CI), 0.91-0.98, 1.21-4.23, 1.51-6.95; P = 0.005, 0.01, 0.003, respectively]. Bleb infection and final visual acuity (logarithm of the minimal angle of resolution) were significantly associated with persistent hypotony (logistic regression: odds ratio, 8.74, 1.37; 95 % CI, 1.89-40.4, 1.03-1.82; P = 0.006, 0.029, respectively). CONCLUSIONS: In the CBIITS, eyes with successful IOP reduction, a limbus-based conjunctival flap, lower preoperative IOP, and choroidal detachment that occurred within 6 months of the surgery were identified as risk factors for persistent hypotony.

Histological findings of uveal capillaries in rabbit eyes after multiple intravitreal injections of bevacizumab.

PURPOSE: To evaluate the potential toxicity of multiple intravitreal injections of bevacizumab on the uveal capillaries of rabbit eyes. MATERIALS AND METHODS: Nine eyes of nine rabbits that received single intravitreal injections of bevacizumab (IVB) constituted the single IVB group, while nine eyes of nine rabbits that received three injections of IVB, with an interval of 28 days between injections, constituted the repeat IVB group. Seven eyes of seven rabbits constituted the control group. The rabbits in the single and repeat IVB groups were sacrificed 7 and 28 d after the single and third IVB injection, respectively. Uveal specimens were compared between groups after immunohistochemical staining. Ultrastructural findings were evaluated by electron microscopy. Control group rabbits were sacrificed 7 d after saline injection. Clinical examination and fundus fluorescein angiography were performed at baseline, 7 d after the first injection, and after the last injection. RESULTS: Differences in the CD31-positive areas of the iris, ciliary body and choroid 7 d after IVB were not statistically significant among the single IVB, repeat IVB and control groups (p = 0.0749, p = 0.7237 and p = 0.7346, respectively; analysis of variance). Endothelial cell fenestrations (ECFs) in the choriocapillaris and ciliary body observed by electron microscopy on day 7 in the single and repeat IVB groups were decreased by 50% (p < 0.0001) and 33% (p < 0.0001), respectively, in both IVB groups compared with those in the control group. However, ECFs observed on day 28 in both groups were comparable to those observed in the control group. CONCLUSIONS: Single IVB and repeated IVB did not have any effect on normal vessel endothelium density as per immunohistochemical findings. Ultrastructural findings revealed that IVB transiently decreased the ECFs in the choriocapillaris and ciliary body.

Comparison of the prevalence of plateau iris configurations between angle-closure glaucoma and open-angle glaucoma using ultrasound biomicroscopy.

PURPOSE: To determine the prevalence of plateau iris configurations in acute primary angle-closure (APAC), chronic angle-closure glaucoma (CACG), and open-angle glaucoma (OAG) eyes using ultrasound biomicroscopy. MATERIALS AND METHODS: The study included fellow eyes of 27 APAC patients, 26 OAG patients, and 26 CACG patients with no history of APAC. Patients with a history of earlier intraocular surgery or argon laser peripheral iridoplasty were excluded from the study. Eyes that had not undergone laser peripheral iridotomy were excluded from APAC and CACG groups. Radial scans were carried out using ultrasound biomicroscopy in all 4 quadrants. A plateau iris configuration within a quadrant was defined by the presence of an anteriorly positioned ciliary process, a narrow ciliary sulcus, a steeply rising peripheral iris, followed by a downward angulation from the corneoscleral wall and the presence of a flat iris plane. Eyes with plateau iris configurations were defined as those having at least 2 quadrants fulfilling these criteria. RESULTS: Plateau iris configurations were found in fellow eyes of 10 of 27 patients with (37.0%) APAC, 9 of 26 (34.6%) patients with CACG, and 5 of 26 (19.2%) patients with OAG. No significant difference in the prevalence of plateau iris configurations was observed among the 3 groups (P=0.314, χ2 test). CONCLUSIONS: Eyes with OAG had a higher rate of plateau iris configurations than expected. Longitudinal studies to evaluate plateau iris height are required to determine its significance in the pathogenesis of angle-closure glaucoma.