Papers by Nyein Chan Lwin
Translational Vision Science & Technology
Scientific Reports
Femtosecond laser-assisted keratoplasty has been proposed as a treatment option for corneal trans... more Femtosecond laser-assisted keratoplasty has been proposed as a treatment option for corneal transplantation. In this study, we investigated and compared the outcomes of Ziemer Z8 femtosecond laser (FSL)-assisted penetrating keratoplasty (PK) using a liquid interface versus flat interface. Thirty fresh porcine eyes underwent FSL-assisted PK with the Z8 using different levels of energies (30%, 90% or 150%) and different interfaces (liquid or flat). The real-time intraocular pressure (IOP) changes, incision geometry, corneal endothelial damage, as well as the accuracy of laser cutting and tissue reaction, were performed and compared. We found that the overall average IOP at all laser trephination stages was significantly higher with the flat interface, regardless of the energy used (68.9 ± 15.0 mmHg versus 46.1 ± 16.6 mmHg; P < 0.001). The overall mean laser-cut angle was 86.2º ± 6.5º and 88.2º ± 1.0º, for the liquid and flat platform respectively, indicating minimal deviation from ...
BMC Ophthalmology, 2022
Background Peripheral iridectomy (PI), routinely performed during glaucoma filtration surgery, ma... more Background Peripheral iridectomy (PI), routinely performed during glaucoma filtration surgery, may contribute to scarring. This study aims to determine whether PI alters the concentrations of VEGF-A and TGF-β isoforms in the rabbit aqueous humour. Methods Anterior chamber paracentesis (ACP) was performed in both eyes of six New Zealand white rabbits, with additional surgical PI performed in the right eyes. Eyes were examined on postoperative days (PODs) 1, 7, 30 and 60 by means of the tonopen, slit-lamp biomicroscopy, and bead-based cytokine assays for TGF-β and VEGF-A concentrations in the aqueous humor. Results ACP caused a significant reduction in intraocular pressure (IOP) from mean preoperative 11.47 ± 1.01 mmHg to 5.67 ± 1.63 mmHg on POD 1 while PI did not cause further IOP reduction. Limbal conjunctival vasculature appeared slightly increased on POD 1 in both ACP and PI eyes with PI also causing mild bleeding from damaged iris vessels. Two PI eyes developed fibrinous anterior...
Investigative Ophthalmology & Visual Science, 2013
Investigative Ophthalmology & Visual Science, 2013
Scientific Reports, 2021
Terahertz (THz) technology has emerged recently as a potential novel imaging modality in biomedic... more Terahertz (THz) technology has emerged recently as a potential novel imaging modality in biomedical fields, including ophthalmology. However, the ocular biological responses after THz electromagnetic exposure have not been investigated. We conducted a rabbit study to evaluate the safety profiles of THz scanning on eyes, at a tissue, cellular, structural and functional level. Eight animals (16 eyes) were analysed after excessive THz exposure (control, 1 h, 4 h, and 1 week after continuous 4-h exposure; THz frequency = 0.3 THz with continuous pulse generated at 40 µW). We found that at all the time points, the corneas and lens remained clear with no corneal haze or lens opacity formation clinically and histopathologically. No thermal effect, assessed by thermographer, was observed. The rod and cone cell-mediated electroretinography responses were not significantly altered, and the corneal keratocytes activity as well as endothelial viability, assessed by in-vivo confocal microscopy, w...
Investigative Ophthalmology & Visual Science, 2015
Translational Vision Science & Technology, 2020
To investigate the postoperative inflammatory and wound-healing responses after laser scleral mic... more To investigate the postoperative inflammatory and wound-healing responses after laser scleral microporation for presbyopia. Methods: Thirty porcine eyes were used for the optimization of laser intensities first. Six monkeys (12 eyes) received scleral microporation with an erbium yttrium aluminum garnet (Er:YAG) laser, and half of the eyes received concurrent subconjunctival collagen gel to modulate wound-healing response. The intraocular pressure (IOP) and the laser ablation depth were evaluated. The animals were euthanized at 1, 6, and 9 months postoperatively. The limbal areas and scleras were harvested for histologic analysis and immunofluorescence of markers for inflammation (CD11b and CD45), wound healing (CD90, tenascin-C, fibronectin, and HSP47), wound contraction (α-smooth muscle actin [α-SMA]), vascular response (CD31), nerve injury (GAP43), and limbal stem cells (P63 and telomerase). Results: In the nonhuman primate study, there was a significant reduction in IOP after the procedure. Overall, the ablation depth was 76.6% to 81.2% at 1 month and slightly decreased to 71.5% to 72.7% at 9 months. Coagulative necrosis around the micropores, as well as expression of CD11b, CD45, tenascin, fibronectin, HSP47, and GAP43, was distinct at 1 month but subsided with time. Collagen gel treatment significantly suppressed the upregulation of CD11b, CD45, fibronectin, and tenascin-C. The expression of CD90, α-SMA, and CD31 was minimal in all eyes. Conclusions: The study demonstrated the course of inflammatory and wound-healing responses following laser scleral microporation. The tissue responses were small and self-limited, resolved with time, and were suppressed by concurrent collagen treatment. It provides a useful understanding of this new procedure. Translational Relevance: The results would be helpful in the laser parameter modification to improve the long-term treatment stability.
Eye and Vision, 2019
Background: Optical coherence tomography angiography (OCTA) is a novel non-invasive angiography t... more Background: Optical coherence tomography angiography (OCTA) is a novel non-invasive angiography technology that has recently been extensively studied for its utility in anterior segment imaging. In this study, we compared a split-spectrum amplitude decorrelation angiography (SSADA) OCTA and an optical micro-angiography (OMAG SD) OCTA system to current angiographic technique, indocyanine green angiography (ICGA), to assess corneal vascularisation in an animal model. Methods: We imaged 16 rabbits, (one eye per animal) with corneal vascularisation using SSADA OCTA (AngioVue; Optovue Inc., USA), OMAG OCTA (Angioscan; RS-3000 Nidek Co. Ltd., Japan) and ICGA in the same region of interest of the cornea at successive time-points. We then analysed all scanned images for vessel density measurements and used paired t-tests and Bland-Altman plots to examine for significant differences. The en-face segmentation images from each of the OCTA scans were also extracted and were matched at every 50 μm segmentation to be compared for vessel density at the respective depths. Results: Bland-Altman plots revealed a good agreement between all three imaging techniques (P > 0.05) for all vessel density measurements computed, and the ranges of 95% limit of agreement were acceptable from a clinical perspective. No significant difference was reported, with ICGA (μ = 16.52 ± 8.94%) being more comparable to the OMAG OCTA (μ = 16.23 ± 9.51%; p = 0.50) than the SSADA OCTA (μ = 17.09 ± 7.34%; p = 0.33) system. Also, a good correlation value (r > 0.9) was obtained when comparing the vessel density measurements of the en-face segmentations between the OCTA systems. Conclusions: Comparable vessel density quantification between the two OCTA systems, and with ICGA was obtained. Segmentation analysis of the vasculature at different depths showed varied performance in the two OCTA systems relative to each other. The implications of the study may help to aid in the development of better OCTA algorithms for the anterior segment and its use in clinical translational research.
Investigative ophthalmology & visual science, Jan 2, 2018
To evaluate the safety and feasibility of intrastromal injection of human corneal stromal keratoc... more To evaluate the safety and feasibility of intrastromal injection of human corneal stromal keratocytes (CSKs) and its therapeutic effect on a rodent early corneal opacity model. Twelve research-grade donor corneas were used in primary culture to generate quiescent CSKs and activated stromal fibroblasts (SFs). Single and repeated intrastromal injections of 2 to 4 × 104 cells to rat normal corneas (n = 52) or corneas with early opacities induced by irregular phototherapeutic keratectomy (n = 16) were performed, followed by weekly examination of corneal response under slit-lamp biomicroscopy and in vivo confocal microscopy with evaluation of haze level and stromal reflectivity, and corneal thickness using anterior segment optical coherence tomography (AS-OCT). Time-lapse tracing of Molday ION-labelled cells was conducted using Spectralis OCT and label intensity was measured. Corneas were collected at time intervals for marker expression by immunofluorescence, cell viability, and apoptos...
Translational vision science & technology, 2018
To compare the postoperative higher-order-aberrations (HOAs) after hyperopic small incision lenti... more To compare the postoperative higher-order-aberrations (HOAs) after hyperopic small incision lenticule extraction (SMILE), hyperopic laser-assisted in situ keratomileusis LASIK), and lenticule implantation for correction of hyperopia. Eighteen monkeys were divided to six groups: +2.00 D and +4.00 D hyperopic SMILE, +2.00 D and +4.00 D hyperopic LASIK ( = 6 eyes for each), and lenticule implantation with a -2.00 D and -4.00 D lenticule ( = 3 eyes for each). The corneal HOAs were evaluated preoperatively and 3-month postoperatively. At 3-month postoperatively, the spherical aberrations significantly increased toward negative direction in all +4.00 D groups (all < 0.05). There was a significant change toward more negative values in the third-order vertical coma in the SMILE +4.00 D and LASIK +4.00 D groups ( = 0.026 and = 0.036, respectively). There were also significant changes in the third-order horizontal trefoil ( = 0.034) and oblique secondary astigmatism ( = 0.012) in the LASIK...
Scientific reports, Jan 30, 2018
Corneal inlays are a relatively new treatment option for presbyopia. Using biological inlays, der... more Corneal inlays are a relatively new treatment option for presbyopia. Using biological inlays, derived from lenticules extracted from small incision lenticule extraction, may offer advantages over commercialized synthetic inlays in the aspect of biocompatibility. We conducted a non-human primate study to evaluate the safety, predictability, efficacy and tissue response after autogeneic, decellularized xenogeneic and xenogeneic lenticule implantation. The lenticule implantation effectively resulted in central corneal steepening (simulated keratometric values increased by 1.8-2.3 diopters), central hyper-prolate changes (asphericity Q values changed by -0.26 to -0.36), corneal anterior surface elevation (7.7-9.3 μm) and reasonable effective zone (1.5-1.8 times of the lenticule physical diameter), with no differences among the three groups. Slit lamp microscopy, transmission electron microscopy, confocal microscopy, histology and immunohistochemistry analyses confirmed the biocompatibil...
Investigative ophthalmology & visual science, Feb 1, 2018
To investigate the drug release profiles of a tacrolimus-loaded poly(D,L-lactide-co-ε-caprolacton... more To investigate the drug release profiles of a tacrolimus-loaded poly(D,L-lactide-co-ε-caprolactone) (PLC) microfilm, and to evaluate its efficacy on the treatment of allergic conjunctivitis using a mouse model. The in vitro and in vivo drug release profiles were first characterized. Balb/c mice were immunized with short ragweed (SRW) injection followed by re-challenges with topical SRW solution. The mice were divided into six groups (n = 12 in each): negative control (NC); positive control (PC); tacrolimus eye drops (Te); subconjunctival tacrolimus microfilm (Tm); dexamethasone eye drops (De); and tacrolimus + dexamethasone eye drops (Te+De). The mice were evaluated for 28 days by a scoring system for allergic conjunctivitis. Histopathologic and immunohistochemical staining with CD11c, CD4, and IL-4 were performed. The microfilms were biocompatible and delivered clinically sufficient dose in a sustained manner, with a steady rate of 0.212 to 0.243 μg/day in vivo. Compared to the PC ...
Investigative Opthalmology & Visual Science, 2017
PURPOSE. Secreted protein acidic and rich in cysteine (SPARC) and Hevin are structurally related ... more PURPOSE. Secreted protein acidic and rich in cysteine (SPARC) and Hevin are structurally related matricellular proteins involved in extracellular matrix assembly. In this study, we compared the anterior chamber biometric parameters and iris collagen properties in SPARC-, Hevin-and SPARC-/Hevin-null with wild-type (WT) mice. The right eyes of 53 WT, 35 SPARC-, 56 Hevin-, and 63 SPARC-/Hevin-null mice were imaged using the RTVue-100 Fourier-domain optical coherence tomography system. The parameters measured were anterior chamber depth (ACD), trabecular-iris space area (TISA), angle opening distance (AOD), and pupil diameter. Biometric data were analyzed using analysis of covariance and adjusted for age, sex, and pupil diameter. Expression of Col1a1, Col8a1, and Col8a2 transcripts in the irises was measured by quantitative polymerase chain reaction. Collagen fibril thickness was evaluated by transmission electron microscopy. Mice that were SPARC-and SPARC-/Hevin-null had 1.28-and 1.25-fold deeper ACD, 1.45-and 1.53-fold larger TISA, as well as 1.42-and 1.51-fold wider AOD than WT, respectively. These measurements were not significantly different between SPARC-and SPARC-/Hevin-null mice. The SPARC-null iris expressed lower Col1a1, but higher Col8a1 and Col8a2 transcripts compared with WT. Collagen fibrils in the SPARC-and SPARC-/Hevin-null irises were 1.5-and 1.7-fold thinner than WT, respectively. The Hevin-null iris did not differ from WT in these collagen properties. CONCLUSIONS. SPARC-null mice have deeper anterior chamber as well as wider drainage angles compared with WT. Therefore, SPARC plays a key role in influencing the spatial organization of the anterior segment, potentially via modulation of collagen properties, while Hevin is not likely to be involved.
PloS one, 2017
Presbyopic inlays have mostly been implanted under a corneal flap. Implantation in a pocket has a... more Presbyopic inlays have mostly been implanted under a corneal flap. Implantation in a pocket has advantages including less postoperative dry eye and neurotrophic effect, and better biomechanical corneal stability. This study investigated the effect of different pocket and flocket dimensions on corneal stability and refractive power after Raindrop™ implantation, and the associated wound healing response. Ten New Zealand White rabbits had bilateral pocket Raindrop™ implantation. Eyes were allocated to 4 groups: pockets with 4mm, 6mm, and 8mm diameters, and 8mm flocket. They were examined pre-operatively, at day 1, weeks 1, 2, 3 and 4 post-surgery with anterior segment optical coherence tomography, corneal topography and in-vivo confocal microscopy. After euthanasia (week 4), CD11b, heat shock protein (HSP) 47 and fibronectin corneal immunohistochemistry was performed. Corneal thickness (mean±SD) increased from 360.0±16.2μm pre-operatively to 383.9±32.5, 409.4±79.3, 393.6±35.2, 396.4±50...
Biomaterials, Mar 1, 2017
Naturally-bioactive hydrogels like gelatin provide favorable properties for tissue-engineering bu... more Naturally-bioactive hydrogels like gelatin provide favorable properties for tissue-engineering but lack sufficient mechanical strength for use as implantable tissue engineering substrates. Complex fabrication or multi-component additives can improve material strength, but often compromises other properties. Studies have shown gelatin methacrylate (GelMA) as a bioactive hydrogel with diverse tissue growth applications. We hypothesize that, with suitable material modifications, GelMA could be employed for growth and implantation of tissue-engineered human corneal endothelial cell (HCEC) monolayer. Tissue-engineered HCEC monolayer could potentially be used to treat corneal blindness due to corneal endothelium dysfunction. Here, we exploited a sequential hybrid (physical followed by UV) crosslinking to create an improved material, named as GelMA+, with over 8-fold increase in mechanical strength as compared to regular GelMA. The presence of physical associations increased the subsequent...
Scientific Reports, 2016
Refractive surgical treatment of hyperopia still remains a challenge for refractive surgeons. A n... more Refractive surgical treatment of hyperopia still remains a challenge for refractive surgeons. A new nomogram of small incision lenticule extraction (SMILE) procedure has recently been developed for the treatment of hyperopia. In the present study, we aimed to evaluate the wound healing and inflammatory responses of this new nomogram (hyperopic-SMILE), and compared them to those of hyperopic-laser-assisted in situ keratomileusis (LASIK), using a rabbit model. A total of 26 rabbits were used, and slit lamp biomicroscopy, autorefractor/keratometer, intraocular pressure measurement, anterior segment optical coherence tomography, corneal topography, and in vivo confocal microscopy examinations were performed during the study period of 4 weeks. The corneas were then harvested and subject to immunofluorescence of markers for inflammation (CD11b), wound healing (fibronectin) and keratocyte response (HSP47). The lenticule ultrastructual changes were also analyzed by transmission electron mic...
Scientific reports, Jul 15, 2016
Recent developments in optical coherence tomography (OCT) systems for the cornea have limited res... more Recent developments in optical coherence tomography (OCT) systems for the cornea have limited resolution or acquisition speed. In this study we aim to evaluate the use of a 'micro-OCT' (μOCT ~1 μm axial resolution) compared to existing imaging modalities using animal models of corneal endothelial disease. We used established cryoinjury and bullous keratopathy models in Sprague Dawley rats comparing ex vivo μOCT imaging in normal and diseased eyes to (1) histology; (2) in vivo confocal microscopy (IVCM); and (3) scanning electron microscopy (SEM). Qualitative and quantitative comparisons amongst imaging modalities were performed using mean endothelial cell circularity [(4π × Area)/Perimeter(2)] with coefficient of variation (COV). We found that μOCT imaging was able to delineate endothelial cells (with nuclei), detect inflammatory cells, and corneal layers with histology-like resolution, comparable to existing imaging modalities. The mean endothelial cell circularity score wa...
Journal of Refractive Surgery, 2016
To investigate the early corneal wound healing and inflammatory responses after small incision le... more To investigate the early corneal wound healing and inflammatory responses after small incision lenticule extraction (SMILE) with different power of corrections and surgical experiences using a rabbit model. Twenty-four rabbits underwent SMILE with -2.00, -4.00, and -8.00 diopters (D) correction. One eye of each rabbit was operated on by surgeon 1 (experienced) and the contralateral eye was operated on by surgeon 2 (novice). Slit-lamp examination, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy were performed at 1 day and 1 week postoperatively. The corneas were harvested for immunofluorescence of markers for inflammation (CD11b), wound healing (fibronectin), and keratocyte response (HSP47). All corneas appeared clear throughout the follow-up period. In vivo confocal microscopy showed a greater reflectivity after -8.00 D than -2.00 D correction at day 1 at the lenticule anterior, posterior, and extracted lenticule planes (surgeon 1: P = .004, .041, and .038; surgeon 2: P = .012, .045, and .031). Different refractive corrections did not significantly affect the expression of CD11b, fibronectin, and HSP47. In the -2.00 D group, eyes operated on by surgeon 2 had thicker central corneal thickness evaluated by AS-OCT (P = .049) and exhibited more CD11b- and HSP47-positive cells at day 1 at the small vertical incision (P = .039 and .042). The early inflammatory and wound healing responses after SMILE were minimal. In the early postoperative period, less surgical experience resulted in an increased inflammatory response in low myopic corrections. Greater keratocyte response was seen in high myopic corrections irrespective of surgeon experience. [J Refract Surg. 2016;32(5):346-353.].
ACS Biomaterials Science & Engineering, 2015
Bacterial infection following implantation of an artificial corneal scaffold is a serious complic... more Bacterial infection following implantation of an artificial corneal scaffold is a serious complication. Conventional antibiotic prophylaxis, which includes topical vancomycin application, is limited by low bioavailability, high dosing requirement, and poor patient compliance. The ideal option to overcome these issues is an antibiotic-eluting corneal prosthesis that sustains the local release of drug. In this study, we incorporated vancomycin in thick 15% collagen hydrogels to create an artificial corneal scaffold with anti-infective capability. The incorporation of vancomycin did not significantly alter the Young's modulus, transparency and refractive index of the vancomycin-loaded hydrogel (VH), which were 0.79 ± 0.04 MPa (p = 0.233 compared to blank hydrogel), 94.3 ± 2.3% (p = 0.115) and 1.346 ± 0.005 (p = 0.264), respectively. In vitro, the drug elution was sustained for up to 7 days. The VH was subsequently implanted intrastromally in rabbit corneas, replacing stromal tissue that was removed following femtosecond laser-assisted small incision lenticule extraction procedure. In vivo, the vancomcyin could be detected in the aqueous humor for up to 10 days. We then created a corneal infectious keratitis model by intrastromal injection of 1 × 108 CFU/ml of Staphylococcus aureus inoculate on day 2 postimplantation. On day 3 postinfection, the VH-implanted corneas were clear and nonedematous and showed a substantial reduction of log 2.5 in S. aureus compared to the blank hydrogel-implanted corneas, which appeared hazy, edematous, and had excessive inflammation. Immunohistochemistry of inflammatory marker, CD18, demonstrated a significant reduction in inflammatory cells in VH-implanted corneas (49 ± 9 cells/unit area) compared to blank hydrogel-implanted corneas (523 ± 15 cells/unit area) (p < 0.001). In conclusion, we have demonstrated the efficacy of a drug-eluting corneal implant in preventing perioperative bacterial infections.
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Papers by Nyein Chan Lwin