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Papers by Yu-chi Liu

Research paper thumbnail of Corneal dendritic cells in diabetes mellitus: A narrative review

Frontiers in Endocrinology, Jan 27, 2023

Diabetes mellitus is a global public health problem with both macrovascular and microvascular com... more Diabetes mellitus is a global public health problem with both macrovascular and microvascular complications, such as diabetic corneal neuropathy (DCN). Using in-vivo confocal microscopy, corneal nerve changes in DCN patients can be examined. Additionally, changes in the morphology and quantity of corneal dendritic cells (DCs) in diabetic corneas have also been observed. DCs are bone marrow-derived antigen-presenting cells that serve both immunological and nonimmunological roles in human corneas. However, the role and pathogenesis of corneal DC in diabetic corneas have not been well understood. In this article, we provide a comprehensive review of both animal and clinical studies that report changes in DCs, including the DC density, maturation stages, as well as relationships between the corneal DCs, corneal nerves, and corneal epithelium, in diabetic corneas. We have also discussed the associations between the changes in corneal DCs and various clinical or imaging parameters, including age, corneal nerve status, and blood metabolic parameters. Such information would provide valuable insight into the development of diagnostic, preventive, and therapeutic strategies for DM-associated ocular surface complications. KEYWORDS corneal dendritic cell, diabetic mellitus, corneal nerves, corneal epithelial cells, in vivo confocal microscopy, diabetic corneal neuropathy, diabetic microvascular complications, ocular surface 1 Diabetes mellitus and diabetic corneal neuropathy Diabetes mellitus (DM), characterised by elevated levels of blood glucose resulting from defective insulin secretion and/or action, has emerged to become a major global public health problem (1). In 2021, 537 million adults were living with diabetes, and estimably 6.7 million adults have died because of DM or its complications (2). The estimated global cost of diabetes

Research paper thumbnail of Sustained-release Drug-eluting Microrods as Ocular Implants

Investigative Ophthalmology & Visual Science, Sep 26, 2016

Research paper thumbnail of The use of TeraHertz scanning system as a quantitative tool in the evaluation of corneal edema

Investigative Ophthalmology & Visual Science, Jun 23, 2017

Research paper thumbnail of Corneal remodelling and topography following biological inlay implantation with combined crosslinking in a rabbit model

Scientific Reports, Mar 14, 2019

Implantation of biological corneal inlays, derived from small incision lenticule extraction, may ... more Implantation of biological corneal inlays, derived from small incision lenticule extraction, may be a feasible method for surgical management of refractive and corneal diseases. However, the refractive outcome is dependent on stromal remodelling of both the inlay and recipient stroma. This study aimed to investigate the refractive changes and tissue responses following implantation of 2.5-mm biological inlays with or without corneal collagen crosslinking (CXL) in a rabbit model. Prior to implantation, rotational rheometry demonstrated an almost twofold increase in corneal stiffness after CXL. After implantation, haze gradually subsided in the CXL-treated inlays (p = 0.001), whereas the untreated inlays preserved their clarity (p = 0.75). In-vivo confocal microscopy revealed reduced keratocyte cell count at the interface of the CXL inlays at week 8. Following initial steepening, regression was observed in anterior mean curvature from week 1 to 12, being most prominent for the non-CXL subgroups (non-CXL: −12.3 ± 2.6D vs CXL: −2.3 ± 4.4D at 90 μm depth, p = 0.03; non-CXL: −12.4 ± 8.0D vs CXL: −5.0 ± 4.0D at 120 μm depth, p = 0.22). Immunohistochemical analysis revealed comparable tissue responses in CXL and untreated subgroups. Our findings suggest that CXL of biological inlays may reduce the time before refractive stabilization, but longer postoperative steroid treatment is necessary in order to reduce postoperative haze.

Research paper thumbnail of High-resolution, non-contact, cellular level imaging of the cornea of the eye in vivo

Optics and Laser Technology, Jun 1, 2022

Research paper thumbnail of The application of Terahertz scanning system on corneas

Investigative Ophthalmology & Visual Science, Jul 22, 2019

Research paper thumbnail of Use of Anterior Segment Optical Coherence Tomography to Predict Corneal Graft Rejection in Small Animal Models

Investigative Ophthalmology & Visual Science, Sep 23, 2014

PURPOSE. To correlate the degree of anterior chamber (AC) inflammation and corneal thickness eval... more PURPOSE. To correlate the degree of anterior chamber (AC) inflammation and corneal thickness evaluated by anterior segment optical coherence tomography (ASOCT) with corneal graft rejection status and to explore the value of ASOCT in assisting the diagnosis or prediction of graft rejection using a rat penetrating keratoplasty (PK) model. METHODS. A total of 40 PKs were performed using Fisher rats (allogeneic groups) and Lewis rats (syngeneic group) as donors and Lewis rats as recipients: isograft control group (n ¼ 10), allograft untreated group (n ¼ 10), and allograft with 1% prednisolone acetate treatment group (n ¼ 20). All the grafts were evaluated for 28 days by a scoring rejection index (RI) to assess the graft opacity, edema, and neovascularization using slit lamp biomicroscopy. The AC inflammation and corneal graft thickness were assessed using ASOCT. RESULTS. All the allogeneic control grafts and four of the 20 allogeneic steroid-treated grafts developed rejection episodes. In the allogeneic treated group, the rejected grafts had a significantly higher mean AC inflammation grade at 1 week (grade 3.25 6 0.49 vs. 1.83 6 0.36, P < 0.001), significantly thicker central graft thickness at 2 weeks (455.25 6 42.42 lm vs. 381.247 6 12.51 lm, P ¼ 0.047), and a significantly higher RI at 4 weeks (7.75 6 0.63 vs. 4.60 6 0.13, P < 0.001) compared to the nonrejected grafts. Eyes with ‡grade 3 AC inflammation at 1 week, or with ‡400 lm central graft thickness at 2 weeks, were significantly associated with graft rejection (odds ratio [OR], 15.15, P ¼ 0.009, and OR, 9.75, P ¼ 0.014, respectively). CONCLUSIONS. The use of ASOCT to evaluate AC inflammation and corneal thickness aids in the early evaluation and diagnosis of graft rejection in animal models. Early increased AC inflammation was an early predictor of graft failure prior to definitive clinical evaluation.

Research paper thumbnail of Advances and Clinical Applications of Anterior Segment Imaging Techniques 2021

Research paper thumbnail of Improvement in Accommodation and Dynamic Range of Focus After Laser Scleral Microporation: A Potential Treatment for Presbyopia

Translational Vision Science & Technology

Research paper thumbnail of Femtosecond laser-assisted corneal transplantation with a low-energy, liquid-interface system

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 ...

Research paper thumbnail of Sustained Prednisolone Acetate-loaded Microfilm Drug Delivery System Effectively Prolongs corneal allograft survival in the rat keratoplasty model

Investigative Ophthalmology & Visual Science, 2013

Research paper thumbnail of Effects of Surgical Experience on Corneal Wound Healing and Inflammatory Responses after Small Incision Lenticule Extraction (SMILE)

Investigative Ophthalmology & Visual Science, 2015

Research paper thumbnail of Corneal Stability of LASIK and SMILE When Combined With Collagen Cross-Linking

Translational Vision Science & Technology, 2019

Purpose: We investigate whether small incision lenticule extraction (SMILE) is associated with le... more Purpose: We investigate whether small incision lenticule extraction (SMILE) is associated with less ectasia than laser-assisted in-situ keratomileusis (LASIK) and whether concomitant collagen cross-linking (CXL) is protective in SMILE Xtra and LASIK Xtra. Methods: Using an established LASIK rabbit ectasia model, we performed À5 diopter (D) LASIK on six eyes and À5 D SMILE on six eyes; five eyes had À5 D LASIK Xtra, five eyes À5 D SMILE Xtra. Anterior segment optical coherence tomography and corneal topography were performed preoperatively and 2, 4, and 6 weeks postoperatively. Mean (standard deviation [SD]) values of postoperative keratometry (K), maximum posterior elevation (MPE) and minimum corneal thickness (CT) were compared to preoperatively and among the surgical groups (paired t-test, analysis of variance). Results: Mean (SD) K values decreased significantly following SMILE, SMILE Xtra, LASIK, and LASIK Xtra. The MPE increased significantly (P , 0.05) following LASIK, SMILE, and SMILE Xtra, but not following LASIK Xtra (P ¼ 0.12). The MPE was less following SMILE than LASIK, but not statistically significant (week 2, 17.73 [5.77] vs. 22.75 [5.05] lm; P ¼ 0.13); post-LASIK Xtra MPE was less than that following LASIK (week 2. 13.39 [3.05] vs. 22.75 [5.05] lm; P , 0.001). CT decreased significantly in all surgical groups; no differences were detected among the groups. Conclusions: SMILE may have less potential than LASIK to induce ectasia. LASIK Xtra and SMILE Xtra showed the smallest increase in MPE. Translational Relevance: Concomitant CXL may be protective following keratorefractive surgery and may reduce further the risk of ectasia.

Research paper thumbnail of Evaluation of drug delivery and biocompatibility of biodegradable microfilms in the anterior segment of the rat model

Investigative Ophthalmology & Visual Science, 2013

Research paper thumbnail of Repeatability and Reproducibility of Corneal Biometric Measurements Using the Visante Omni and a Rabbit Experimental Model of Post-Surgical Corneal Ectasia

Translational Vision Science & Technology, Apr 28, 2015

To investigate the repeatability and reproducibility of the Visante Omni topography in obtaining ... more To investigate the repeatability and reproducibility of the Visante Omni topography in obtaining topography measurements of rabbit corneas and to develop a post-surgical model of corneal ectasia. Methods: Eight rabbits were used to study the repeatability and reproducibility by assessing the intra-and interobserver bias and limits of agreement. Another nine rabbits underwent different diopters (D) of laser in situ keratosmileusis (LASIK) were used for the development of ectasia model. All eyes were examined with the Visante Omni, and corneal ultrastructure were evaluated with transmission electron microscopy (TEM). Results: There was no significant intra-or interobserver difference for mean steep and flat keratometry (K) values of simulated K, anterior, and posterior elevation measurements. Eyes underwent À5 D LASIK had a significant increase in mean amplitude of astigmatism and posterior surface elevation with time (P for trend , 0.05). At 2 and 3 months, the À5 D LASIK group had significant greater mean amplitude of astigmatism (P ¼ 0.036; P ¼ 0.027) and posterior surface elevation (both P , 0.005) compared with control group. On TEM, the mean collagen fibril diameter and interfibril distance in the À5 D LASIK eyes were significantly greater than in controls at 3 months (P ¼ 0.018; P , 0.001). Conclusions: The Visante Omni provided imaging of the rabbit cornea with good repeatability and reproducibility. Application of À5 D LASIK treatment produced a rabbit model of corneal ectasia that was gradual in development and simulated the human condition. Translational Relevance: The results provide the foundations for the future evaluation of novel treatment modalities for post-surgical ectasia and keratoconus.

Research paper thumbnail of Descemet’s stripping automated endothelial keratoplasty and penetrating keratoplasty for Fuchs’ endothelial dystrophy

Acta Ophthalmologica, 2009

To compare the outcome of Descemet&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s stripping en... more To compare the outcome of Descemet&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s stripping endothelial keratoplasty (DSAEK) to that of penetrating keratoplasty (PK) in patients with Fuchs&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; endothelial dystrophy. The first 20 patients who underwent DSAEK at the Department of Ophthalmology, Aarhus University Hospital were compared to 20 patients treated with classic PK. Best-corrected visual acuity, subjective spectacle refraction and corneal thickness were registered before surgery and 1, 3, 6 and 12 months after DSAEK surgery; they were also measured before surgery and 12 months and 2-3 years after PK. Endothelial cell density was measured 12 months after surgery in both groups. Two primary graft failures were observed in the DSAEK group; no failures were seen in the PK group. Best spectacle-corrected visual acuity (BSCVA) at 12 months after surgery was significantly better in the DSAEK group (0.56 +/- 0.04) than in the PK group (0.33 +/- 0.06). At this time, 70% of the DSAEK-treated eyes but only 25% of PK-treated eyes had obtained a BSCVA of 0.5 or better. Two to three years after surgery, BSCVA was 0.5 or better in 55% of PK-treated eyes. Refractive ametropia and astigmatism were significantly smaller in DSAEK-treated eyes than in PK-treated eyes, even after suture removal and arcuate keratotomy. Endothelial cell density (cells/mm2) after 1 year was lower in DSAEK-treated (1.338 +/- 113) than in PK-treated eyes (1.610 +/- 124), but the difference was not statistically significant. DSAEK seems to be superior to PK in treating Fuchs&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; endothelial keratoplasty, although primary graft failure may be more common. Visual recovery is faster, and major ametropia and astigmatism is not induced. Long-term follow-up studies are essential to assess whether this conclusion also holds true more than 1 year after surgery.

Research paper thumbnail of Reshaping and Customization of SMILE-Derived Biological Lenticules for Intrastromal Implantation

Investigative Opthalmology & Visual Science, 2018

PURPOSE. To evaluate the feasibility of excimer laser reshaping of biological lenticules availabl... more PURPOSE. To evaluate the feasibility of excimer laser reshaping of biological lenticules available after small incision lenticule extraction (SMILE). METHODS. Fresh and cryopreserved SMILE-derived human lenticules underwent excimer laser ablation for stromal reshaping. The treatment effects in the lasered group were compared with the nonlasered group with respect to changes in surface functional groups (by Fourier transform infrared spectroscopy [FTIR]) and surface morphology (by scanning electron microscopy [SEM] and atomic force microscopy [AFM]). Ten SMILE-derived porcine lenticules, five nonlasered (107-lm thick, À6 diopter [D] spherical power) and five excimer lasered (50% thickness reduction), were implanted into a 120-lm stromal pocket of 10 porcine eyes. Corneal thickness and topography were assessed before and after implantation. RESULTS. FTIR illustrated prominent changes in the lipid profile. The collagen structure was also affected by the laser treatment but to a lesser extent. SEM exhibited a more regular surface for the lasered lenticules, confirmed by the lower mean R z value (290.1 6 96.1 nm vs. 380.9 6 92.6 nm, P ¼ 0.045) on AFM. The lasered porcine lenticules were thinner than the nonlasered controls during overhydration (132 6 26 lm vs. 233 6 23 lm, P < 0.001) and after 5 hours in a moist chamber (46 6 3 lm vs. 57 6 3 lm, P < 0.001). After implantation, the nonlasered group showed a tendency toward a greater increase in axial keratometry (6.63 6 2.17 D vs. 5.60 6 3.79 D, P ¼ 0.613) and elevation (18.6 6 15.4 vs. 15.2 6 5.5, P ¼ 0.656) than the lasered group. CONCLUSIONS. Excimer laser ablation may be feasible for thinning and reshaping of SMILEderived lenticules before reimplantation or allogenic transplantation. However, controlled lenticule dehydration before ablation is necessary in order to allow stromal thinning.

Research paper thumbnail of Application of Novel Drugs for Corneal Cell Regeneration

Journal of ophthalmology, 2018

Corneal transplantation has been the only treatment method for corneal blindness, which is the ma... more Corneal transplantation has been the only treatment method for corneal blindness, which is the major cause of reversible blindness. However, despite the advancement of surgical techniques for corneal transplantation, demand for the surgery can never be met due to a global shortage of donor cornea. The development of bioengineering and pharmaceutical technology provided us with novel drugs and biomaterials that can be used for innovative treatment methods for corneal diseases. In this review, the authors will discuss the efficacy and safety of pharmacologic therapies, such as Rho-kinase (ROCK) inhibitors, blood-derived products, growth factors, and regenerating agent on corneal cell regeneration. The promising results of these agents suggest that these can be viable options for corneal reconstruction and visual rehabilitation.

Research paper thumbnail of Corneal lenticule storage before reimplantation

Molecular vision, 2017

To explore the optimal lenticule storage conditions that maintain lenticule integrity and clarity... more To explore the optimal lenticule storage conditions that maintain lenticule integrity and clarity. A total of 99 lenticules obtained from myopic patients undergoing small incision lenticule extraction (SMILE) were divided into four combinations for short-term storage conditions: PBS, Dulbecco's Modified Eagle's Medium (DMEM), Optisol GS, or anhydrous glycerol. Two thirds of the lenticules were further stored for 4 weeks under eight different conditions. Clarity evaluation with transmittance measurements, cell-death assays with terminal deoxynucleotidyl transferase-mediated nick end labeling assay (TUNEL), collagen fibril spacing and necrotic response assessed with transmission electron microscopy (TEM), and immunohistochemistry analysis for human leukocyte antigens (HLAs) and CD45 for immunogenicity, and matrix metalloproteinase (MMP)-2 for keratocyte response, were undertaken at baseline, 48 h (short term), and 4 weeks (long term). The TUNEL and immunogenicity results were ...

Research paper thumbnail of Higher-Order-Aberrations Following Hyperopia Treatment: Small Incision Lenticule Extraction, Laser-Assisted In Situ Keratomileusis and Lenticule Implantation

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...

Research paper thumbnail of Corneal dendritic cells in diabetes mellitus: A narrative review

Frontiers in Endocrinology, Jan 27, 2023

Diabetes mellitus is a global public health problem with both macrovascular and microvascular com... more Diabetes mellitus is a global public health problem with both macrovascular and microvascular complications, such as diabetic corneal neuropathy (DCN). Using in-vivo confocal microscopy, corneal nerve changes in DCN patients can be examined. Additionally, changes in the morphology and quantity of corneal dendritic cells (DCs) in diabetic corneas have also been observed. DCs are bone marrow-derived antigen-presenting cells that serve both immunological and nonimmunological roles in human corneas. However, the role and pathogenesis of corneal DC in diabetic corneas have not been well understood. In this article, we provide a comprehensive review of both animal and clinical studies that report changes in DCs, including the DC density, maturation stages, as well as relationships between the corneal DCs, corneal nerves, and corneal epithelium, in diabetic corneas. We have also discussed the associations between the changes in corneal DCs and various clinical or imaging parameters, including age, corneal nerve status, and blood metabolic parameters. Such information would provide valuable insight into the development of diagnostic, preventive, and therapeutic strategies for DM-associated ocular surface complications. KEYWORDS corneal dendritic cell, diabetic mellitus, corneal nerves, corneal epithelial cells, in vivo confocal microscopy, diabetic corneal neuropathy, diabetic microvascular complications, ocular surface 1 Diabetes mellitus and diabetic corneal neuropathy Diabetes mellitus (DM), characterised by elevated levels of blood glucose resulting from defective insulin secretion and/or action, has emerged to become a major global public health problem (1). In 2021, 537 million adults were living with diabetes, and estimably 6.7 million adults have died because of DM or its complications (2). The estimated global cost of diabetes

Research paper thumbnail of Sustained-release Drug-eluting Microrods as Ocular Implants

Investigative Ophthalmology & Visual Science, Sep 26, 2016

Research paper thumbnail of The use of TeraHertz scanning system as a quantitative tool in the evaluation of corneal edema

Investigative Ophthalmology & Visual Science, Jun 23, 2017

Research paper thumbnail of Corneal remodelling and topography following biological inlay implantation with combined crosslinking in a rabbit model

Scientific Reports, Mar 14, 2019

Implantation of biological corneal inlays, derived from small incision lenticule extraction, may ... more Implantation of biological corneal inlays, derived from small incision lenticule extraction, may be a feasible method for surgical management of refractive and corneal diseases. However, the refractive outcome is dependent on stromal remodelling of both the inlay and recipient stroma. This study aimed to investigate the refractive changes and tissue responses following implantation of 2.5-mm biological inlays with or without corneal collagen crosslinking (CXL) in a rabbit model. Prior to implantation, rotational rheometry demonstrated an almost twofold increase in corneal stiffness after CXL. After implantation, haze gradually subsided in the CXL-treated inlays (p = 0.001), whereas the untreated inlays preserved their clarity (p = 0.75). In-vivo confocal microscopy revealed reduced keratocyte cell count at the interface of the CXL inlays at week 8. Following initial steepening, regression was observed in anterior mean curvature from week 1 to 12, being most prominent for the non-CXL subgroups (non-CXL: −12.3 ± 2.6D vs CXL: −2.3 ± 4.4D at 90 μm depth, p = 0.03; non-CXL: −12.4 ± 8.0D vs CXL: −5.0 ± 4.0D at 120 μm depth, p = 0.22). Immunohistochemical analysis revealed comparable tissue responses in CXL and untreated subgroups. Our findings suggest that CXL of biological inlays may reduce the time before refractive stabilization, but longer postoperative steroid treatment is necessary in order to reduce postoperative haze.

Research paper thumbnail of High-resolution, non-contact, cellular level imaging of the cornea of the eye in vivo

Optics and Laser Technology, Jun 1, 2022

Research paper thumbnail of The application of Terahertz scanning system on corneas

Investigative Ophthalmology & Visual Science, Jul 22, 2019

Research paper thumbnail of Use of Anterior Segment Optical Coherence Tomography to Predict Corneal Graft Rejection in Small Animal Models

Investigative Ophthalmology & Visual Science, Sep 23, 2014

PURPOSE. To correlate the degree of anterior chamber (AC) inflammation and corneal thickness eval... more PURPOSE. To correlate the degree of anterior chamber (AC) inflammation and corneal thickness evaluated by anterior segment optical coherence tomography (ASOCT) with corneal graft rejection status and to explore the value of ASOCT in assisting the diagnosis or prediction of graft rejection using a rat penetrating keratoplasty (PK) model. METHODS. A total of 40 PKs were performed using Fisher rats (allogeneic groups) and Lewis rats (syngeneic group) as donors and Lewis rats as recipients: isograft control group (n ¼ 10), allograft untreated group (n ¼ 10), and allograft with 1% prednisolone acetate treatment group (n ¼ 20). All the grafts were evaluated for 28 days by a scoring rejection index (RI) to assess the graft opacity, edema, and neovascularization using slit lamp biomicroscopy. The AC inflammation and corneal graft thickness were assessed using ASOCT. RESULTS. All the allogeneic control grafts and four of the 20 allogeneic steroid-treated grafts developed rejection episodes. In the allogeneic treated group, the rejected grafts had a significantly higher mean AC inflammation grade at 1 week (grade 3.25 6 0.49 vs. 1.83 6 0.36, P < 0.001), significantly thicker central graft thickness at 2 weeks (455.25 6 42.42 lm vs. 381.247 6 12.51 lm, P ¼ 0.047), and a significantly higher RI at 4 weeks (7.75 6 0.63 vs. 4.60 6 0.13, P < 0.001) compared to the nonrejected grafts. Eyes with ‡grade 3 AC inflammation at 1 week, or with ‡400 lm central graft thickness at 2 weeks, were significantly associated with graft rejection (odds ratio [OR], 15.15, P ¼ 0.009, and OR, 9.75, P ¼ 0.014, respectively). CONCLUSIONS. The use of ASOCT to evaluate AC inflammation and corneal thickness aids in the early evaluation and diagnosis of graft rejection in animal models. Early increased AC inflammation was an early predictor of graft failure prior to definitive clinical evaluation.

Research paper thumbnail of Advances and Clinical Applications of Anterior Segment Imaging Techniques 2021

Research paper thumbnail of Improvement in Accommodation and Dynamic Range of Focus After Laser Scleral Microporation: A Potential Treatment for Presbyopia

Translational Vision Science & Technology

Research paper thumbnail of Femtosecond laser-assisted corneal transplantation with a low-energy, liquid-interface system

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 ...

Research paper thumbnail of Sustained Prednisolone Acetate-loaded Microfilm Drug Delivery System Effectively Prolongs corneal allograft survival in the rat keratoplasty model

Investigative Ophthalmology & Visual Science, 2013

Research paper thumbnail of Effects of Surgical Experience on Corneal Wound Healing and Inflammatory Responses after Small Incision Lenticule Extraction (SMILE)

Investigative Ophthalmology & Visual Science, 2015

Research paper thumbnail of Corneal Stability of LASIK and SMILE When Combined With Collagen Cross-Linking

Translational Vision Science & Technology, 2019

Purpose: We investigate whether small incision lenticule extraction (SMILE) is associated with le... more Purpose: We investigate whether small incision lenticule extraction (SMILE) is associated with less ectasia than laser-assisted in-situ keratomileusis (LASIK) and whether concomitant collagen cross-linking (CXL) is protective in SMILE Xtra and LASIK Xtra. Methods: Using an established LASIK rabbit ectasia model, we performed À5 diopter (D) LASIK on six eyes and À5 D SMILE on six eyes; five eyes had À5 D LASIK Xtra, five eyes À5 D SMILE Xtra. Anterior segment optical coherence tomography and corneal topography were performed preoperatively and 2, 4, and 6 weeks postoperatively. Mean (standard deviation [SD]) values of postoperative keratometry (K), maximum posterior elevation (MPE) and minimum corneal thickness (CT) were compared to preoperatively and among the surgical groups (paired t-test, analysis of variance). Results: Mean (SD) K values decreased significantly following SMILE, SMILE Xtra, LASIK, and LASIK Xtra. The MPE increased significantly (P , 0.05) following LASIK, SMILE, and SMILE Xtra, but not following LASIK Xtra (P ¼ 0.12). The MPE was less following SMILE than LASIK, but not statistically significant (week 2, 17.73 [5.77] vs. 22.75 [5.05] lm; P ¼ 0.13); post-LASIK Xtra MPE was less than that following LASIK (week 2. 13.39 [3.05] vs. 22.75 [5.05] lm; P , 0.001). CT decreased significantly in all surgical groups; no differences were detected among the groups. Conclusions: SMILE may have less potential than LASIK to induce ectasia. LASIK Xtra and SMILE Xtra showed the smallest increase in MPE. Translational Relevance: Concomitant CXL may be protective following keratorefractive surgery and may reduce further the risk of ectasia.

Research paper thumbnail of Evaluation of drug delivery and biocompatibility of biodegradable microfilms in the anterior segment of the rat model

Investigative Ophthalmology & Visual Science, 2013

Research paper thumbnail of Repeatability and Reproducibility of Corneal Biometric Measurements Using the Visante Omni and a Rabbit Experimental Model of Post-Surgical Corneal Ectasia

Translational Vision Science & Technology, Apr 28, 2015

To investigate the repeatability and reproducibility of the Visante Omni topography in obtaining ... more To investigate the repeatability and reproducibility of the Visante Omni topography in obtaining topography measurements of rabbit corneas and to develop a post-surgical model of corneal ectasia. Methods: Eight rabbits were used to study the repeatability and reproducibility by assessing the intra-and interobserver bias and limits of agreement. Another nine rabbits underwent different diopters (D) of laser in situ keratosmileusis (LASIK) were used for the development of ectasia model. All eyes were examined with the Visante Omni, and corneal ultrastructure were evaluated with transmission electron microscopy (TEM). Results: There was no significant intra-or interobserver difference for mean steep and flat keratometry (K) values of simulated K, anterior, and posterior elevation measurements. Eyes underwent À5 D LASIK had a significant increase in mean amplitude of astigmatism and posterior surface elevation with time (P for trend , 0.05). At 2 and 3 months, the À5 D LASIK group had significant greater mean amplitude of astigmatism (P ¼ 0.036; P ¼ 0.027) and posterior surface elevation (both P , 0.005) compared with control group. On TEM, the mean collagen fibril diameter and interfibril distance in the À5 D LASIK eyes were significantly greater than in controls at 3 months (P ¼ 0.018; P , 0.001). Conclusions: The Visante Omni provided imaging of the rabbit cornea with good repeatability and reproducibility. Application of À5 D LASIK treatment produced a rabbit model of corneal ectasia that was gradual in development and simulated the human condition. Translational Relevance: The results provide the foundations for the future evaluation of novel treatment modalities for post-surgical ectasia and keratoconus.

Research paper thumbnail of Descemet’s stripping automated endothelial keratoplasty and penetrating keratoplasty for Fuchs’ endothelial dystrophy

Acta Ophthalmologica, 2009

To compare the outcome of Descemet&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s stripping en... more To compare the outcome of Descemet&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s stripping endothelial keratoplasty (DSAEK) to that of penetrating keratoplasty (PK) in patients with Fuchs&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; endothelial dystrophy. The first 20 patients who underwent DSAEK at the Department of Ophthalmology, Aarhus University Hospital were compared to 20 patients treated with classic PK. Best-corrected visual acuity, subjective spectacle refraction and corneal thickness were registered before surgery and 1, 3, 6 and 12 months after DSAEK surgery; they were also measured before surgery and 12 months and 2-3 years after PK. Endothelial cell density was measured 12 months after surgery in both groups. Two primary graft failures were observed in the DSAEK group; no failures were seen in the PK group. Best spectacle-corrected visual acuity (BSCVA) at 12 months after surgery was significantly better in the DSAEK group (0.56 +/- 0.04) than in the PK group (0.33 +/- 0.06). At this time, 70% of the DSAEK-treated eyes but only 25% of PK-treated eyes had obtained a BSCVA of 0.5 or better. Two to three years after surgery, BSCVA was 0.5 or better in 55% of PK-treated eyes. Refractive ametropia and astigmatism were significantly smaller in DSAEK-treated eyes than in PK-treated eyes, even after suture removal and arcuate keratotomy. Endothelial cell density (cells/mm2) after 1 year was lower in DSAEK-treated (1.338 +/- 113) than in PK-treated eyes (1.610 +/- 124), but the difference was not statistically significant. DSAEK seems to be superior to PK in treating Fuchs&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; endothelial keratoplasty, although primary graft failure may be more common. Visual recovery is faster, and major ametropia and astigmatism is not induced. Long-term follow-up studies are essential to assess whether this conclusion also holds true more than 1 year after surgery.

Research paper thumbnail of Reshaping and Customization of SMILE-Derived Biological Lenticules for Intrastromal Implantation

Investigative Opthalmology & Visual Science, 2018

PURPOSE. To evaluate the feasibility of excimer laser reshaping of biological lenticules availabl... more PURPOSE. To evaluate the feasibility of excimer laser reshaping of biological lenticules available after small incision lenticule extraction (SMILE). METHODS. Fresh and cryopreserved SMILE-derived human lenticules underwent excimer laser ablation for stromal reshaping. The treatment effects in the lasered group were compared with the nonlasered group with respect to changes in surface functional groups (by Fourier transform infrared spectroscopy [FTIR]) and surface morphology (by scanning electron microscopy [SEM] and atomic force microscopy [AFM]). Ten SMILE-derived porcine lenticules, five nonlasered (107-lm thick, À6 diopter [D] spherical power) and five excimer lasered (50% thickness reduction), were implanted into a 120-lm stromal pocket of 10 porcine eyes. Corneal thickness and topography were assessed before and after implantation. RESULTS. FTIR illustrated prominent changes in the lipid profile. The collagen structure was also affected by the laser treatment but to a lesser extent. SEM exhibited a more regular surface for the lasered lenticules, confirmed by the lower mean R z value (290.1 6 96.1 nm vs. 380.9 6 92.6 nm, P ¼ 0.045) on AFM. The lasered porcine lenticules were thinner than the nonlasered controls during overhydration (132 6 26 lm vs. 233 6 23 lm, P < 0.001) and after 5 hours in a moist chamber (46 6 3 lm vs. 57 6 3 lm, P < 0.001). After implantation, the nonlasered group showed a tendency toward a greater increase in axial keratometry (6.63 6 2.17 D vs. 5.60 6 3.79 D, P ¼ 0.613) and elevation (18.6 6 15.4 vs. 15.2 6 5.5, P ¼ 0.656) than the lasered group. CONCLUSIONS. Excimer laser ablation may be feasible for thinning and reshaping of SMILEderived lenticules before reimplantation or allogenic transplantation. However, controlled lenticule dehydration before ablation is necessary in order to allow stromal thinning.

Research paper thumbnail of Application of Novel Drugs for Corneal Cell Regeneration

Journal of ophthalmology, 2018

Corneal transplantation has been the only treatment method for corneal blindness, which is the ma... more Corneal transplantation has been the only treatment method for corneal blindness, which is the major cause of reversible blindness. However, despite the advancement of surgical techniques for corneal transplantation, demand for the surgery can never be met due to a global shortage of donor cornea. The development of bioengineering and pharmaceutical technology provided us with novel drugs and biomaterials that can be used for innovative treatment methods for corneal diseases. In this review, the authors will discuss the efficacy and safety of pharmacologic therapies, such as Rho-kinase (ROCK) inhibitors, blood-derived products, growth factors, and regenerating agent on corneal cell regeneration. The promising results of these agents suggest that these can be viable options for corneal reconstruction and visual rehabilitation.

Research paper thumbnail of Corneal lenticule storage before reimplantation

Molecular vision, 2017

To explore the optimal lenticule storage conditions that maintain lenticule integrity and clarity... more To explore the optimal lenticule storage conditions that maintain lenticule integrity and clarity. A total of 99 lenticules obtained from myopic patients undergoing small incision lenticule extraction (SMILE) were divided into four combinations for short-term storage conditions: PBS, Dulbecco's Modified Eagle's Medium (DMEM), Optisol GS, or anhydrous glycerol. Two thirds of the lenticules were further stored for 4 weeks under eight different conditions. Clarity evaluation with transmittance measurements, cell-death assays with terminal deoxynucleotidyl transferase-mediated nick end labeling assay (TUNEL), collagen fibril spacing and necrotic response assessed with transmission electron microscopy (TEM), and immunohistochemistry analysis for human leukocyte antigens (HLAs) and CD45 for immunogenicity, and matrix metalloproteinase (MMP)-2 for keratocyte response, were undertaken at baseline, 48 h (short term), and 4 weeks (long term). The TUNEL and immunogenicity results were ...

Research paper thumbnail of Higher-Order-Aberrations Following Hyperopia Treatment: Small Incision Lenticule Extraction, Laser-Assisted In Situ Keratomileusis and Lenticule Implantation

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...