Electrospun PLLA Nanofiber Scaffolds and Their Use in Combination with BMP-2 for Reconstruction of Bone Defects

Introduction Adequate migration and differentiation of mesenchymal stem cells is essential for regeneration of large bone defects. To achieve this, modern graft materials are becoming increasingly important. Among them, electrospun nanofiber scaffolds are a promising approach, because of their high physical porosity and potential to mimic the extracellular matrix (ECM). Materials and Methods The objective of the present study was to examine the impact of electrospun PLLA nanofiber scaffolds on bone formation in vivo, using a critical size rat calvarial defect model. In addition we analyzed whether direct incorporation of bone morphogenetic protein 2 (BMP-2) into nanofibers could enhance the osteoinductivity of the scaffolds. Two critical size calvarial defects (5 mm) were created in the parietal bones of adult male Sprague-Dawley rats. Defects were either (1) left unfilled, or treated with (2) bovine spongiosa, (3) PLLA scaffolds alone or (4) PLLA/BMP-2 scaffolds. Cranial CT-scans were taken at fixed intervals in vivo. Specimens obtained after euthanasia were processed for histology, histomorphometry and immunostaining (Osteocalcin, BMP-2 and Smad5). Results PLLA scaffolds were well colonized with cells after implantation, but only showed marginal ossification. PLLA/BMP-2 scaffolds showed much better bone regeneration and several ossification foci were observed throughout the defect. PLLA/BMP-2 scaffolds also stimulated significantly faster bone regeneration during the first eight weeks compared to bovine spongiosa. However, no significant differences between these two scaffolds could be observed after twelve weeks. Expression of osteogenic marker proteins in PLLA/BMP-2 scaffolds continuously increased throughout the observation period. After twelve weeks osteocalcin, BMP-2 and Smad5 were all significantly higher in the PLLA/BMP-2 group than in all other groups. Conclusion Electrospun PLLA nanofibers facilitate colonization of bone defects, while their use in combination with BMP-2 also increases bone regeneration in vivo and thus combines osteoconductivity of the scaffold with the ability to maintain an adequate osteogenic stimulus

Supplementary Material for: Descemet Membrane Detachment Triggered by Contrast-Enhanced Computed Tomography in a Patient with History of Penetrating Keratoplasty for Keratoconus Treatment

Introduction: We report a case of late-onset Descemet membrane detachment triggered by contrast-enhanced computed tomography more than 30 years after penetrating keratoplasty for keratoconus and describe its successful treatment with air tamponade. Case Presentation: A 53-year-old woman with a history of uneventful penetrating keratoplasty more than 30 years ago for keratoconus presented with acute vision loss caused by corneal edema 2 days after undergoing contrast-enhanced computed tomography. Anterior segment optical coherence tomography (AS-OCT) revealed corneal stromal edema in the graft and Descemet’s fold, and partial Descemet membrane detachment without a tear. The patient received 0.1% betamethasone eye drops once every hour, along with sub-Tenon’s triamcinolone acetonide injection. Anti-inflammatory treatment improved corneal edema; however, the detachment area widened. Air tamponade facilitated complete Descemet membrane reattachment and improved corneal thickness with complete restoration of visual acuity. Conclusion: An immune response may have been involved in the progression of Descemet membrane detachment in this patient. Anti-inflammatory treatment may have facilitated Descemet membrane reattachment prior to air or gas tamponade. AS-OCT is an excellent imaging modality to detect Descemet membrane detachment in eyes with presumed late penetrating graft rejection or failure

Visual acuity loss associated with excessive “dry macula” in exudative age-related macular degeneration

10.2147/OPTH.S151999Clinical Ophthalmology12369-37

Visual acuity loss associated with excessive “dry macula” in exudative age-related macular degeneration

Hidenori Takahashi,1–3 Yuji Inoue,1,2 Xue Tan,2,3 Satoru Inoda,1 Shinichi Sakamoto,1 Yusuke Arai,1 Yasuo Yanagi,4–6 Yujiro Fujino,2,3 Hidetoshi Kawashima1 1Department of Ophthalmology, Jichi Medical University, Shimotsuke, 2Department of Ophthalmology, The University of Tokyo, Bunkyo, 3Department of Ophthalmology, Japan Community Health Care Organization Tokyo Shinjuku Medical Center, Shinjuku, Japan; 4Medical Retina, Singapore National Eye Centre, 5Medical Retina, Singapore Eye Research Institute, 6Eye-ACP, Duke NUS Medical School, National University of Singapore, Singapore Purpose: To investigate the correlation between visual acuity and central macular thickness (CMT) and choroidal thickness (CCT) in patients with wet age-related macular degeneration (AMD). Methods: In this retrospective analysis, 14 eyes that received >10 ranibizumab injections (based on pro re nata [PRN] regimen) and maintained initial visual acuity gain were analyzed. The following 5 parameters were measured at the foveal center: CMT (distance from the inner limiting membrane [ILM] to Bruch’s membrane); central retinal thickness (CRT; distance from the ILM to the inner limit of the retinal pigment epithelium or subretinal fluid [SRF]); SRF thickness (SRFT); pigment epithelium detachment thickness (PEDT); and CCT. The correlation between the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) and the 5 parameters was examined with generalized estimating equations. Results: CMT, CRT, and CCT were negatively correlated with logMAR BCVA (P=0.031, 0.023, and 0.036, respectively) when only CMT values less than the thickness that maximized visual acuity for each eye were used for the analysis. Each 100-µm reduction in CMT, CRT, or CCT improved logMAR BCVA by -0.1, -0.08, or -0.07, respectively. SRFT and PEDT were not correlated with BCVA. The median CMT that maximized the visual acuity was 230 µm. Conclusion: Dry macula with CMT <230 µm was associated with temporary decrease in visual acuity in AMD patients whose visual acuity was maintained with PRN regimen. Keywords: age-related macular degeneration, intravitreal injections, ranibizumab, visual acuity, dry macul

Intravitreal aflibercept for exudative age-related macular degeneration with good visual acuity: 2-year results of a prospective study

Shinichi Sakamoto,1 Hidenori Takahashi,1,2 Yuji Inoue,1 Yusuke Arai,1 Satoru Inoda,1 Natsuko Kakinuma,2 Yujiro Fujino,2 Tatsuro Tanabe,2 Hidetoshi Kawashima,1 Yasuo Yanagi3–5 1Department of Ophthalmology, Jichi Medical University, Shimotsuke-shi, Tochigi, Japan; 2Department of Ophthalmology, Japan Community Health Care Organization Tokyo Shinjuku Medical Center, Tokyo, Japan; 3Medical Retina, Singapore National Eye Centre, Singapore; 4Medical Retina, Singapore Eye Research Institute, Singapore; 5Eye-ACP, Duke NUS Medical School, National University of Singapore, Singapore Purpose: We report the 2-year outcomes of intravitreal aflibercept (IVA) for exudative age-related macular degeneration (AMD) with good visual acuity (VA) and examine the baseline factors associated with good visual outcome. Materials and methods: This multicenter, prospective study evaluated 39 eyes (39 AMD patients) enrolled from August 2013 to August 2014 at 12 and 24 months. Only patients with initial best-corrected VA (BCVA) >0.3 logarithm of the minimum angle of resolution (20/40 Snellen) were eligible. Three consecutive monthly IVA injections were followed by 2 monthly injections for 12 months. Thereafter, patients received injections on a treat-and-extend regimen for up to 24 months. Outcome measures included BCVA and central macular thickness (CMT) at 12 and 24 months. Post hoc analysis, BCVA, and CMT were evaluated by AMD types (typical AMD [tAMD], type 1, and type 2 polypoidal choroidal vasculopathy [PCV]). Baseline characteristics and BCVA associations were evaluated with linear regression analysis and Student’s t-test. Results: Mean age was 69 years and 26 of 39 eyes were male. tAMD, type 1 and type 2 PCV occurred in 18, 12, and 9 eyes, respectively. Baseline mean BCVA was 0.097 logarithm of the minimum angle of resolution (20/25 Snellen) and showed significant improvement to 0.058 (20/22 Snellen, P=0.03) at 12 months and 0.066 (20/23) at 24 months. CMT improved significantly from 320 (99) µm (mean [SD]) to 250 (93) µm (P=0.002) at 12 months and 240 (93) µm (P=0.0005) at 24 months. BCVA and CMT were not significantly different among the three groups. Only subretinal hemorrhage (SRH) was significantly associated with improved BCVA. BCVA change from baseline was -0.12 with SRH and -0.011 without SRH (P=0.017) at 12 months. Conclusion: IVA showed good efficacy for exudative AMD with good VA at 24 months. tAMD and type 1 and 2 PCV showed similar prognosis. Baseline SRH predicted favorable long-term vision in AMD with good VA. Keywords: polypoidal choroidal vasculopathy, aflibercept, age-related macular degeneration, fixed regimen, good visual acuity, prospective study, treat-and-exten

Intravitreal aflibercept for exudative age-related macular degeneration with good visual acuity: 2-year results of a prospective study

10.2147/OPTH.S160961Clinical Ophthalmology121137-114