Serum sclerostin level is positively associated with endothelial dysfunction measured by digital thermal monitoring in patients with type 2 diabetes: A prospective cross-sectional study.

Sclerostin and dickkopf-1 (DKK1), extracellular inhibitors of the canonical Wnt/ß-catenin signaling pathway, have been associated with vascular aging and atherosclerosis. This study aimed to assess the correlation of sclerostin and DKK1 concentrations with endothelial function measured using vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples were collected from 100 patients with T2DM. Endothelial function and VRI were measured using digital thermal monitoring and circulating sclerostin and DKK1 levels by enzyme-linked immunosorbent assays. VRI values < 1.0, 1.0-1.9, and > 2.0 indicated poor, intermediate, and good vascular reactivity, respectively. Overall, 30, 38, and 32 patients had poor, intermediate, and good vascular reactivity, respectively. Older age, higher serum glycated hemoglobulin, urinary albumin-to-creatinine ratio, and sclerostin as well as lower hypertension prevalence, systolic blood pressure, and diastolic blood pressure (DBP) were associated with poor VRI. Multivariable forward stepwise linear regression analysis showed that DBP (ß = 0.294, adjusted R2 change = 0.098, P < .001), log-glycated hemoglobin (ß = -0.235, adjusted R2 change = 0.050, P = .002), log-urine albumin-to-creatinine ratio (ß = -0.342, adjusted R2 change = 0.227, P < .001), and log-sclerostin level (ß = -0.327, adjusted R2 change = 0.101, P < .001) were independently associated with VRI. Serum sclerostin, along with glycated hemoglobin and albumin-to-creatinine ratio, exhibited a negative correlation with VRI, while DBP showed a positive correlation with VRI. These factors can independently predict endothelial dysfunction in patients with T2DM.

Ophthalmic characteristics and retinal vasculature changes in Williams syndrome, and its association with systemic diseases.

BACKGROUND: We aim to characterise the ophthalmic findings and retinal vasculature changes in patients with WS, and to analyse the correlation between ophthalmic manifestations and the associated systemic diseases. METHODS: This retrospective case-control study included 27 WS patients and 28 age-matched healthy participants. Stellate pattern of iris, central macular thickness (CMT), foveal width, retinal vessel diameter, superficial vascular density (SVD) of macula and foveal avascular zone (FAZ) were compared between WS patients and healthy participants. RESULTS: Twenty-five patients (93%) had the classic stellate iris presentation. Compared with healthy controls, WS patients had decreased CMT, increased foveal width and a lower SVD of macula (all P < 0.001). Significantly decreased mean retinal arterial (117.9 ± 9.9 µm vs. 133.0 ± 6.7 µm in WS and controls, respectively; p < 0.001) and venous (158.9 ± 11.2 µm vs. 174.0 ± 8.0 µm in WS and controls, respectively; p < 0.001) outer diameters, as well as mean arterial wall thickness (11.2 ± 1.3 µm vs. 12.2 ± 0.8 µm in WS and controls, respectively; p < 0.01) were found in WS. Stellate iris grading was significantly associated with CMT, foveal width, retinal vessel diameter (all p < 0.05), and a significant increase in the odds of having hypertension (Odds ratio (OR), 5.63; P < 0.05). The severity of stellate iris in WS seemed to have the trend of increasing risk of having pulmonary stenosis, tricuspid regurgitation and mitral regurgitation. CONCLUSIONS: This study provides the first in vivo evidence reflecting current knowledge on vessel morphology in WS patients that deficient circumferential growth is the predominant pathophysiologic changes resulting from elastin deficiency. The ophthalmic characteristics may serve as a complementary tool to diagnose and follow-up patients suffering from WS.

Bleb-related infection after primary trabeculectomy: medical chart reviews from 1993 to 2021.

BACKGROUND: To investigate the incidence of and risk factors for bleb-related infection (BRI) in patients who underwent mitomycin C-augmented primary trabeculectomy. METHODS: We reviewed the medical charts of consecutive patients who had received primary trabeculectomy in Taipei Veterans General Hospital. We recorded the demographic and clinical characteristics of patients before, during and after surgery. Furthermore, we recorded the time interval between surgery and infection onset, clinical manifestations and visual outcomes of patients with BRI. The cumulative incidence of BRI was estimated using the Kaplan-Meier method. A Cox proportional hazards model was used to explore factors associated with BRI. RESULTS: In total, 1663 eyes were postoperatively followed up for 94.57±65.23 months. The cumulative incidence of BRI was 1.86 per 1000 person-years during the 28-year follow-up period: 24 (1.44%) patients developed BRI and 6 (0.36%) patients additionally developed endophthalmitis. A multivariate analysis revealed a significant association of BRI with wound manipulation, high myopia and hyperlipidaemia. Patients younger than 60 years were more likely to receive wound manipulation than their elderly counterparts (<0.001). One year after BRI, the best corrected visual acuity of the eyes with blebitis did not change significantly, whereas that of the eyes with endophthalmitis worsened significantly. CONCLUSION: Risk factors for BRI after trabeculectomy include wound manipulation, high myopia and hyperlipidaemia. Considering myopia is highly prevalent throughout the world and is a risk factor for glaucoma, the lifelong risk of BRI after trabeculectomy in eyes with high myopia warrants the attention of ophthalmologists.

Pseudophakic pupillary block after phacoemulsification and posterior chamber intraocular lens implantation: Cause identification and treatment refinement.

BACKGROUND: Pseudophakic pupillary block (PPB) was rare in patients who undergo phacoemulsification and posterior chamber intraocular lens (PCIOL) implantation. Laser peripheral iridotomy was the most reported but ineffective treatment in the literature. METHODS: Retrospective, interventional case series of patients who developed PPB in Taipei Veterans General Hospital from 2017 to 2021. Clinical course, diagnostic methods, treatment and outcomes were recorded and discussed. RESULTS: Four eyes of three patients were documented. All of them had diabetes and diabetic retinopathy. Anterior segment Optical coherence tomography (OCT) of these patients showed an exudative membrane at the peripapillary area while slit lamp image could not provide a clear view due to the severely edematous corneal condition. Laser peripheral iridotomy and yttrium aluminum garnet (YAG) laser aiming to the peripapillary exudation were applied to break the PPB successfully. CONCLUSION: Diabetes mellitus, intravitreal injection and inflammation are crucial risk factors for PPB. Anterior segment OCT can be a useful diagnostic tool for the detection of the peripapillary exudative membrane while corneal clarity is compromised due to high intraocular pressure. In addition to peripheral laser iridotomy, an effective approach to resolve PPB may be the use of the YAG laser to break the exudative membrane.

Physical, Chemical, and Biological Properties of Chitosan-Coated Alginate Microparticles Loaded with Porcine Interleukin-1ß: A Potential Protein Adjuvant Delivery System.

We previously developed chicken interleukin-1ß (IL-1ß) mutants as single-dose adjuvants that induce protective immunity when co-administered with an avian vaccine. However, livestock such as pigs may require a vaccine adjuvant delivery system that provides long-lasting protection to reduce the need for successive booster doses. Therefore, we developed chitosan-coated alginate microparticles as a carrier for bovine serum albumin (BSA) or porcine IL-1ß (pIL-1ß) and assessed their physical, chemical, and biological properties. Electrospraying of the BSA-loaded alginate microparticles (BSA/ALG MPs) resulted in an encapsulation efficiency of 50%, and those MPs were then coated with chitosan (BSA/ALG/CHI MPs). Optical and scanning electron microscopy, zeta potential analysis, and Fourier transform infrared spectroscopy were used to characterize these MPs. The BSA encapsulation parameters were applied to ALG/CHI MPs loaded with pIL-1ß, which were not cytotoxic to porcine fibroblasts but had enhanced bio-activity over unencapsulated pIL-1ß. The chitosan layer of the BSA/ALG/CHI MPs prevented burst release and facilitated sustained release of pIL-1ß for at least 28 days. In conclusion, BSA/ALG/CHI MPs prepared as a carrier for pIL-1ß may be used as an adjuvant for the formulation of pig vaccines.

Late capsular blockage syndrome: Clinical and anterior segment optical coherence tomography characteristics.

BACKGROUND: Late capsular blockage syndrome (CBS) is a rare phenomenon which is found after cataract surgery. The mechanism, anterior segment optical coherence tomography (OCT) presentation, and clinical characteristics are not well studied. METHODS: We studied patients who developed late CBS in Taipei Veterans General Hospital from 2012 to 2019. Age, sex, systemic disease, ocular disease, interval between cataract surgery and CBS, axial length, type of intraocular lens implanted, grading of posterior capsular opacity, refraction, visual acuity, and anterior segment OCT findings were documented. Patients are categorized into two groups according to anterior segment OCT findings. All patients underwent Nd:YAG laser capsulotomy and were prescribed a low-dose topical steroid for 7 days. Postcapsulotomy refraction and visual acuity were recorded. All the clinical data were compared in the two groups. RESULTS: This study included 18 eyes with late CBS. Patients' median age was 80 (range, 54-92) years. The mean duration between cataract surgery and CBS diagnosis was 80.28 (range 15-136) months. According to anterior segment OCT findings, we subcategorized the patients into two groups: gravel appearance (n = 7) and milky (n = 11) appearance. After laser capsulotomy, mean visual acuity improved 0.18 ± 0.10 on the LogMAR. A significant myopic shift in refraction after laser capsulotomy was noted in the gravel appearance group compared to the milky appearance group ( p = 0.027). No patient developed complications or needed further treatment for CBS during the median follow-up of 14.5 months (range 1-84 months). CONCLUSION: High-resolution anterior segment OCT is useful for analyzing patients with late CBS. Our study implies that the two types of CBS presentation indicate different causes of late CBS formation, as well as distinct clinical presentation and postlaser capsulotomy refractive outcome. In addition, YAG laser capsulotomy is a safe late CBS treatment modality.

Refractive status, biometric components, and functional outcomes of patients with threshold retinopathy of prematurity: systemic review and a 17-year longitudinal study.

OBJECTIVE: To assess the long-term refractive status, visual outcome, astigmatism, and the change in biometric optic components in older adolescents up to age 17 years with threshold retinopathy of prematurity (ROP) treated with diode laser. METHODS: A retrospective, longitudinal study in which cycloplegic refraction, keratometry, and the biometric measurement of optic components were performed on 28 consecutive preterm eyes with laser-treated threshold ROP at age 17 years. The study results were statistically analysed and compared with age-matched full-term control. RESULTS: All patients with ROP had myopia (average spherical equivalent of - 6.35 D, ranges from - 1.25 to - 12.38 D), and 12 eyes (43%) were highly myopic (spherical equivalent < - 6.0 D). Threshold ROP eyes exhibited a significantly poorer visual acuity (P < 0.001), greater cylinder refractive error (P < 0.001), higher corneal astigmatism (P < 0.001), and flatter horizontal corneal curvature (P = 0.01) compared with age-matched controls. Biometric optic components analysis revealed a significant shallower anterior chamber depth (P < 0.001), thicker lens (P < 0.001), and shorter axial length (P = 0.021) in laser-treated ROP eyes compared with age-matched controls. CONCLUSIONS: In this 17-year longitudinal study, a higher prevalence of myopia and astigmatism was observed in laser-treated threshold ROP eyes compared with age-matched control eyes. Myopia and astigmatism in laser-treated ROP eyes typically progress through adolescence after school age. Therefore, we recommend that preterm patients with laser-treated threshold ROP should attend regular follow-up not only for refractive status but also for structural change of anterior segment until their adolescence.

Management of Delayed Complications of Hydrogel Scleral Buckles.

(1) Background: hydrogel scleral buckles (HSB)-related complications can happen decades after implantation, although this material has been retrieved for a long time. Due to its fragile texture, ensuring the complete removal of this material and avoiding complications are challenging. Incomplete removal, iatrogenic complication, recurrent retinal detachment, and infection could occur. (2) Methods: chart review of patients who developed delayed HSB-related complications and received removal of HSB in Taipei Veterans General Hospital from 2004 to 2021. The presenting symptoms, prior diagnosis before referral, clinical findings, image features, surgical technique, operative findings, and outcome were analyzed. Detailed surgical procedure and tips for removal were demonstrated in the study. (3) Results: a total of eleven patients were identified. The presenting symptoms include limitations to extraocular movement (ten eyes, 90.9%), ocular redness (eight eyes, 72.7%), ocular fullness (eight eyes, 72.7%), pain (six eyes, 54.5%), and exposed ocular foreign body (five eyes, 45.5%). Of note, six patients (54.5%) have monocular glaucoma and four of them have intractable high intraocular pressure. All patients underwent surgeries to smoothly remove swollen HSB via transcutaneous or transconjunctival approach. Most symptoms improved after surgery and no cases developed surgical-related complications. (4) Conclusions: although HSB have been off the market for decades, delayed complications are still emerging. Clinicians should remain alert for potential complications for patients with prior HSB surgeries. Early diagnosis and meticulous management can help to safely remove the expanded HSB and reduce the associated complications.

Traumatic aniridia with extensive episcleral pigmentation: a case report.

BACKGROUND: Traumatic aniridia has been documented in eyes with a history of cataract extraction through a clear corneal wound. The proposed hypothesis is that the iris tissue was squeezed out from the corneal wound as it is a relative weak point. However, traumatic aniridia with extensive pigmentation of the episclera has never been reported. CASE PRESENTATION: A patient, who has surgical histories of trabeculectomy and cataract surgery many years ago, presented with refractory high intraocular pressure (IOP), almost complete loss of the iris, and diffuse pigmentation of the episclera after he had suffered from a contusion injury. In addition to numerous pigment particles and cells in the anterior chamber and a well-centered intraocular lens, protruding uvea tissue with overlying conjunctiva adjacent to the site of trabeculectomy was noted. Gonioscopy showed absence of the iris with clear view of the ciliary body. CONCLUSIONS: The distinct presentation of this case indicates that the torn iris was displaced to the trapdoor instead of the clear cornea incision and was confined to the subconjunctival space. The scleral fistula serves as a less resistant point for releasing pressure compared to a healed corneal wound when the eye encounters a contusion injury. Further treatment options to lower IOP include repeated trabeculectomy, implantation of glaucoma drainage device, and endoscopic cyclophotocoagulation. Transscleral cyclophotocoagulation may be considered only after episcleral pigmentation has become less so as to avoid the risk of surface burn.

Structural Insight into the Contributions of the N-Terminus and Key Active-Site Residues to the Catalytic Efficiency of Glutamine Synthetase 2.

Glutamine synthetase (GS) catalyzes the condensation of ammonia and glutamate, along with ATP, to form glutamine. Despite extensive studies on GSs from eukaryotes and prokaryotes, the roles of the N-terminus and other structural features in catalysis remain unclear. Here we report the decameric structure of Drosophila melanogaster GS 2 (DmGS2). The N-terminal short helices, α1 and α2, constitute a meander region, and form hydrogen bonds with residues 3-5 in the N-terminal loop, which are not present in the GSs of other species. Deletion of α1 or α1-α2 inactivates DmGS2. Notably, the Arg4 in each monomer of one pentamer forms hydrogen bonds with Glu7, and Asp8 in the adjacent monomer of the other pentamer. Replacement of Arg4 with Asp (R4D) abolishes activity. Analytical ultracentrifugation revealed that Arg4 is crucial for oligomerization. Circular dichroism spectra revealed that R4D may alter the secondary structure. We mutated key residues to identify the substrate-binding site. As Glu140 binds glutamate and Glu311 binds ammonia, mutants E140A and E311A have little activity. Conversely, mutant P214A (P contributes to ATP binding) has higher activity than wild-type DmGS2. These findings expand the understanding of the structural and functional features of the N-terminal meander region of DmGS2 and the residues important for catalytic efficiency.

Optical coherence tomography-based diabetic macula edema screening with artificial intelligence.

BACKGROUND: Optical coherence tomography (OCT) is considered as a sensitive and noninvasive tool to evaluate the macular lesions. In patients with diabetes mellitus (DM), the existence of diabetic macular edema (DME) can cause significant vision impairment and further intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) is needed. However, the increasing number of DM patients makes it a big burden for clinicians to manually determine whether DME exists in the OCT images. The artificial intelligence (AI) now enormously applied to many medical territories may help reduce the burden on clinicians. METHODS: We selected DME patients receiving IVI of anti-VEGF or corticosteroid at Taipei Veterans General Hospital in 2017. All macular cross-sectional scan OCT images were collected retrospectively from the eyes of these patients from January 2008 to July 2018. We further established AI models based on convolutional neural network architecture to determine whether the DM patients have DME by OCT images. RESULTS: Based on the convolutional neural networks, InceptionV3 and VGG16, our AI system achieved a high DME diagnostic accuracy of 93.09% and 92.82%, respectively. The sensitivity of the VGG16 and InceptionV3 models was 96.48% and 95.15%., respectively. The specificity was corresponding to 86.67% and 89.63% for VGG16 and InceptionV3, respectively. We further developed an OCT-driven platform based on these AI models. CONCLUSION: We successfully set up AI models to provide an accurate diagnosis of DME by OCT images. These models may assist clinicians in screening DME in DM patients in the future.

Carboxylated nanodiamond-mediated CRISPR-Cas9 delivery of human retinoschisis mutation into human iPSCs and mouse retina.

Nanodiamonds (NDs) are considered to be relatively safe carbon nanomaterials used for the transmission of DNA, proteins and drugs. The feasibility of utilizing the NDs to deliver CRISPR-Cas9 system for gene editing has not been clearly studied. Therefore, in this study, we aimed to use NDs as the carriers of CRISPR-Cas9 components designed to introduce the mutation in RS1 gene associated with X-linked retinoschisis (XLRS). ND particles with a diameter of 3 nm were functionalized by carboxylation of the surface and covalently conjugated with fluorescent mCherry protein. Two linear DNA constructs were attached to the conjugated mCherry: one encoded Cas9 endonuclease and GFP reporter, another encoded sgRNA and contained insert of HDR template designed to introduce RS1 c.625C>T mutation. Such nanoparticles were successfully delivered and internalized by human iPSCs and mouse retinas, the efficiency of internalization was significantly improved by mixing with BSA. The delivery of ND particles led to introduction of RS1 c.625C>T mutation in both human iPSCs and mouse retinas. Rs1 gene editing in mouse retinas resulted in several pathological features typical for XLRS, such as aberrant photoreceptor structure. To conclude, our ND-based CRISPR-Cas9 delivery system can be utilized as a tool for creating in vitro and in vivo disease models of XLRS. STATEMENT OF SIGNIFICANCE: X-linked retinoschisis (XLRS) is a prevalent hereditary retinal disease, which is caused by mutations in RS1 gene, whose product is important for structural organization of the retina. The recent development of genome editing techniques such as CRISPR-Cas9 significantly improved the prospects for better understanding the pathology and development of treatment for this disease. Firstly, gene editing can allow development of appropriate in vitro and in vivo disease models; secondly, CRISPR-Cas9 can be applied for gene therapy by removing the disease-causative mutation in vivo. The major prerequisite for these approaches is to develop safe and efficient CRISPR-Cas9 delivery system. In this study, we tested specifically modified nanodiamonds for such a delivery system. We were able to introduce Rs1 mutation into the mouse retina and, importantly, observed several XLRS-specific effects.

Dietary Supplementation with Hazelnut Oil Reduces Serum Hyperlipidemia and Ameliorates the Progression of Nonalcoholic Fatty Liver Disease in Hamsters Fed a High-Cholesterol Diet.

Objective: Hazelnut oil (HO) is rich in monounsaturated fatty acids and polyunsaturated fatty acids. This study intended to analyze the effects of hazelnut oil supplementation on the serum lipid profile and nonalcoholic fatty liver disease in hamsters fed a high-cholesterol (HC) diet. Methods: Hamsters were fed a basic diet (control group) and an HC diet (HC group) for 16 weeks (n = 10 in each group). Hamsters were fed an HC diet for four weeks to induce hyperlipidemia and were then fed an HC diet enriched with 5% (low-dose HC + HO group; n = 10) and 10% HO (high-dose HC + HO group; n = 10) for 12 weeks. Serum lipid levels, hepatic changes (including steatosis, inflammation, and fibrosis), and hepatic prooxidant-antioxidant status (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione S-transferase (GST)) were evaluated after the treatment period. Results: Hamsters in the control group showed normal serum lipid profiles, normal liver function, and moderate glycogen storage without hepatic steatosis. Hamsters in the HC group showed severe hyperlipidemia, severe hepatic steatosis, and moderate steatohepatitis (mononuclear cell and neutrophil infiltration, oval cell hyperplasia, and fibrosis). Compared to the HC group, both the low-dose and the high-dose HC + HO groups showed a significant reduction of hyperlipidemia (serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and very-low-density lipoprotein cholesterol (VLDL-C levels)) and improved liver function (serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT)). Additionally, compared to the HC group, intrahepatic triglyceride accumulation (IHTC) was significantly higher in the HC + HO group, while the incidence of steatohepatitis was significantly lower. The intake of the HC diet was associated with a higher level of lipid peroxidation (malondialdehyde, MDA) and a lower concentration of hepatic antioxidant enzymes (SOD, GPx, and GST), and all these factors were partially improved in the low-dose and high-dose HC + HO groups. Conclusions: Our findings indicate that the intake of HO reduced serum hyperlipidemia and oxidative stress and ameliorated the progression of nonalcoholic fatty liver disease in hamsters fed a high-cholesterol diet.

Diagnostic ability of macular ganglion cell asymmetry in Preperimetric Glaucoma.

BACKGROUND: To evaluate the diagnostic ability of macular ganglion cell asymmetry to diagnose preperimetric glaucoma (PPG), using Cirrus spectral domain optical coherence tomography (OCT). METHODS: This prospective study included 67 eyes of 67 patients with PPG and 67 eyes of 67 age- and refractive error-matched controls. We measured circumpapillary RNFL (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness and optic nerve head (ONH) parameters using OCT. Macular ganglion cell asymmetries were expressed as absolute difference and ratios between inferior hemisphere and superior hemisphere, inferotemporal (IT) and superotemporal (ST), IT and superonasal (SN), IT and inferonasal (IN), ST and IN as well as temporal and nasal. An asymmetry index was assigned by taking the absolute value of log10 of the ratio. The area under the receiver operating characteristics curve (AUROC), partial AUROC (pAUROC) ≥ specificities 90 and 95%, cutoff values and sensitivities at specificities 90 and 95% was analyzed. RESULTS: Parameters with largest AUROCs were IT GCIPL thickness (0.784), average RNFL thickness (0.767), and average C/D (0.746). For macular asymmetry parameters, log IT/SN index had the largest AUROC (0.734), followed by log IT/IN index (0.725), and absolute difference of IT-SN GCIPL thickness (0.715). Performance was comparable between the best measures of asymmetry analysis (log IT/SN index) and those of cpRNFL, GCIPL, and ONH parameters (all P > 0.05). The IT/SN asymmetry index not only had the largest pAUROC based on the pAUROCs ≥90 and 95% specificity (0.044 and 0.019) but also had the highest diagnostic sensitivity at 90 and 95% specificities (52.2 and 46.3%). CONCLUSIONS: GCIPL asymmetry measurements have diagnostic ability comparable to cpRNFL, GCIPL, and ONH analysis for PPG. The best macular ganglion cell asymmetry parameter was IT/SN asymmetry index, which could be a new parameter to detect early structural changes in PPG.

Correlation between sclerostin and Dickkopf-1 with aortic arterial stiffness in patients with type 2 diabetes: A prospective, cross-sectional study.

BACKGROUND: Sclerostin and Dickkopf-1 are extracellular inhibitors of the canonical Wnt/ß-catenin signalling pathway, which is implicated in the development of arterial stiffness. However, the correlation between aortic stiffness and sclerostin or Dickkopf-1 levels in patients with type 2 diabetes mellitus is unknown. METHODS: Fasting blood samples were collected from 125 patients with type 2 diabetes mellitus. Aortic stiffness was measured by carotid-femoral pulse wave velocity, and high aortic stiffness was defined by a carotid-femoral pulse wave velocity of >10 m/s. The serum sclerostin and Dickkopf-1 concentrations were determined using commercially available enzyme-linked immunosorbent assays. RESULTS: In total, 46 patients with type 2 diabetes mellitus (36.8%) had high levels of aortic stiffness. Compared to the control group without aortic stiffness, this group was significantly older, had higher systolic and diastolic blood pressures, had higher blood urea nitrogen, creatinine, urinary albumin-to-creatinine ratio and serum sclerostin levels, and had significantly lower high-density lipoprotein cholesterol levels and estimated glomerular filtration rates. After adjusting for confounders, serum sclerostin [odds ratio = 1.005 (1.002-1.007), p = 0.002] levels remained an independent predictor of aortic stiffness. Multivariate analysis showed that the serum sclerostin level ( ß = 0.374, adjusted R2 change = 0.221, p < 0.001) was positively associated with carotid-femoral pulse wave velocity. CONCLUSION: Serum levels of sclerostin, but not Dickkopf-1, are positively correlated with carotid-femoral pulse wave velocity and independently predict aortic stiffness in patients with type 2 diabetes mellitus.

Macular ganglion cell asymmetry for detecting paracentral scotoma in early glaucoma.

PURPOSE: We evaluated macular ganglion cell asymmetry as a tool for diagnosing paracentral scotoma (PCS) in early glaucoma. PATIENTS AND METHODS: This prospective study compared 58 patients with early glaucoma and PCS to 58 age-matched control individuals. All glaucomatous eyes had scotoma within the central 12 degrees of fixation and confined to one hemifield. We measured circumpapillary retinal nerve fiber layer (cpRNFL) thickness, macular ganglion cell-inner plexiform layer (GCIPL) thickness, and optic nerve head (ONH) parameters with Cirrus spectral domain optical coherence tomography. Macular ganglion cell asymmetry was expressed as the absolute differences and the ratios between the inferior and superior hemispheres, inferotemporal (IT) and superotemporal (ST) areas, IT and superonasal (SN) areas, IT and inferonasal (IN) areas, and ST and IN areas. The asymmetry index was the absolute log10 of the ratio. The area under the receiver operating characteristics curve (AUROC) and partial AUROC (pAUROC, specificities ≥90%) were analyzed for each parameter. RESULTS: All GCIPL parameters and most cpRNFL parameters were significantly lower in early glaucoma than in controls. The best discriminating parameters were inferior RNFL thickness, average RNFL thickness, and minimum GCIPL thickness. The macular ganglion cell asymmetry parameters with the largest AUROCs were the log IT/ST index, the absolute difference in IT-ST GCIPL thicknesses, and the log IT/SN index. Performance was comparable between the log IT/ST index and the cpRNFL (inferior RNFL thickness, P=0.129), GCIPL (minimum GCIPL thickness, P=0.358), and ONH parameters (vertical cup-to-disc ratio, P=0.475). CONCLUSION: The IT/ST asymmetry index may be useful as a new parameter for detecting structural changes in glaucoma patients with PCS.

Development of a full thickness macular hole after vitrectomy for rhegmatogenous retinal detachment: a sequential study via optical coherence tomography.

BACKGROUND: To demonstrate a full thickness macular hole (MH) development after vitrectomy (VT) for rhegmatogenous retinal detachment (RRD) and to investigate the possible disease mechanism with optical coherence tomography (OCT). CASE PRESENTATION: A 47-year-old female underwent 23G vitrectomy surgery to repair the macula-detached RRD successfully. However, intraretinal cysts initially developed two months after surgery. Cysts gradually increased in number and size, and cystoid macular edema was noted at the 5th month. Thereafter, inner retina dehiscence and a lamellar macular hole developed. The lamellar hole further dehisced and progressed into a full-thickness MH at the 10th month. The patient then received 23G vitrectomy and internal limiting membrane peeling surgery. OCT and fundus picture showed macular hole sealed 10 days afterward. CONCLUSIONS: The mechanism of secondary MH included tangential traction, cystoid degeneration of macula, and glial migration. The sequential OCT studies provide evidence to support the disease mechanism of cystoid degeneration of the macula.

Conjunctival papilloma: Clinical features, outcome, and factors related to recurrence.

PURPOSE: The purpose of the study was to evaluate the clinical features, treatment, and outcome of patients with conjunctival papilloma. MATERIALS AND METHODS: Twenty-two patients (22 eyes) with biopsy-proven conjunctival papilloma between January 2005 and January 2015 in a tertiary medical center were retrospectively reviewed. Clinical profiles, treatment, outcome, and factors related to recurrence were evaluated. RESULTS: There were 16 males (73%) and 6 females (27%), with a mean age of 47 years. The most common location of conjunctival papilloma was the caruncle (43%), followed by palpebral conjunctiva (29%), bulbar conjunctiva (14%), and fornix (14%). Recurrence developed in five patients (22.7%). The risk of postoperative recurrence was significantly related to the presence of bulbar conjunctival papilloma with corneal involvement (P = 0.043) and surgical excision alone (P = 0.039). One case with multiple recurrences developed nonkeratinizing carcinoma. Two young females developed conjunctival papilloma even after receiving human papillomavirus vaccinations. CONCLUSION: The recurrence of conjunctival papilloma is not uncommon, especially for those patients underwent surgical excision alone. Surgical excision with adjunctive therapy and long-term follow-up is rational for the treatment of conjunctival papilloma.