Alginate Hydrogel Integrated with a Human Fibroblast-Derived Extracellular Matrix Supports Corneal Endothelial Cell Functionality and Suppresses Endothelial-Mesenchymal Transition.

Human corneal transplantation is still the only option to restore the function of corneal endothelial cells (CECs). Therefore, there is an urgent need for hCEC delivery systems to replace the human donor cornea. Here, we propose an alginate hydrogel (AH)-based delivery system, where a human fibroblast-derived, decellularized extracellular matrix (ECM) was physically integrated with AH. This AH securely combined with the ECM (ECM-AH) was approximately 50 µm thick, transparent, and permeable. The surface roughness and surface potential provided ECM-AH with a favorable microenvironment for CEC adhesion and growth in vitro. More importantly, ECM-AH could support the structural (ZO-1) and functional (Na+/K+-ATPase) markers of hCECs, as assessed via western blotting and quantitative polymerase chain reaction, which were comparable with those of a ferritic nitrocarburizing (FNC)-coated substrate (a positive control). The cell density per unit area was also significantly better with ECM-AH than the FNC substrate at day 7. A simulation test of cell engraftment in vitro showed that hCECs were successfully transferred into the decellularized porcine corneal tissue, where they were mostly alive. Furthermore, we found out that the endothelial-mesenchymal transition (EnMT)-inductive factors (Smad2 and vimentin) were largely declined with the hCECs grown on ECM-AH, whereas the EnMT inhibitory factor (Smad7) was significantly elevated. The difference was statistically significant compared to that of the FNC substrate. Moreover, we also observed that TGF-ß1-treated hCECs showed faster recovery of cell phenotype on the ECM. Taken together, our study demonstrates that ECM-AH is a very promising material for hCEC culture and delivery, which endows an excellent microenvironment for cell function and phenotype maintenance.

Late spontaneous posterior capsule rupture with single-piece hydrophobic acrylic intraocular lens dislocation.

In this study, we described and discussed the late onset spontaneous posterior capsule rupture with intraocular lens (IOL) dislocation years after uncomplicated cataract surgery and implantation of hydrophobic acrylic IOLs. Eight patients presented with spontaneous posterior capsule rupture and IOL dislocation 5-20 years after uncomplicated phacoemulsification and IOL (AcrySof, Alcon, US) implantation. None of the patients had undergone posterior capsulotomy in the past. Four of the patients admitted habitual eye rubbing. An intact and well-centered continuous curvilinear capsulotomy edge was observed in all cases. IOLs were dislocated or displaced behind the anterior capsulotomy with a significant decrease in vision. A large rupture with a curled edge of the broken posterior capsule was visible. Dislocated IOLs were removed, and a three-piece IOL was inserted in the sulcus in six cases and suture fixated to the sclera in two cases. Improved vision was achieved in all cases. Although the mechanism underlying this late complication is unclear, habitual eye rubbing or IOL design may play a role. Further investigation is needed to prevent this complication in the future.

Nitric oxide: an old drug but with new horizons in ophthalmology-a narrative review.

Background and Objective: Based on basic knowledge and prior research on nitric oxide (NO), the potential of NO for treating eye diseases is reviewed, and the possibility of NO-based eye drops in clinical practice and the future potential of NO in ophthalmology are discussed. Methods: A PubMed search was performed for English-language original reports and reviews using the following key words: nitric oxide, eye, ocular, and drug. Key Content and Findings: NO is synthesized in the human body by NO synthase (NOS) from L-arginine or through enzyme-dependent reduction of dietary nitrate. Three types of NOS (eNOS, nNOS, and iNOS) are abundantly expressed in the eye under normal physiologic or pathologic conditions. The biological effect of NO in the eye is dose dependent. Low intraocular NO concentrations, produced by eNOS or nNOS, have various cellular effects, including vasodilation, intraocular pressure (IOP) regulation, and neuroprotection. iNOS induced under pathologic ocular conditions produces high NO concentrations in the local environment and mediates tissue inflammation, ocular cell apoptosis, and neurodegeneration. In particular, increased iNOS has been reported in glaucoma and retinal ischemic or degenerative diseases. NO plays a vital role in ocular injury. NO can facilitate ocular surface wound healing while eradicating pathogens such as bacteria and Acanthamoeba in chemical burns or infectious keratitis. Furthermore, NO has antifibrotic activity via the cyclic guanosine monophosphate (cGMP) signaling pathway. NO causes smooth muscle relaxation, which can be used to inhibit myopia progression in children. NO can be a stem cell modulator and may help in treating ocular stem cell disorders. Conclusions: Because of its diverse biologic effects, NO can be a key player in regulating ocular inflammation in various ocular diseases, aiding ocular surface wound healing, controlling IOP in glaucoma, alleviating retinal disease, and suppressing myopia progression. Although there remain limitations to the effective use of highly unstable state, gaseous NO, the role of NO in the field of ophthalmology can be greatly expanded through the development of novel NO donors and effective delivery platforms.

Effects of In Vitro Combination of Nitric Oxide Donors and Hypochlorite on Acanthamoeba castellanii Viability.

Purpose: To investigate the combined anti-Acanthamoeba effects of nitric oxide (NO) donors and hypochlorite to maximize amoebicidal outcomes while minimizing damage to human corneal epithelial cells (HCECs). Methods: Acanthamoeba castellanii and primary cultured HCECs and keratocytes were treated with sodium hypochlorite (NaOCl), NO donors (sodium nitroprusside [SNP] and sodium nitrite [NaNO2]), or a combination of hypochlorite and NO donors. The viability of A. castellanii, HCECs, and keratocytes was assessed. Minimal inhibitory concentration (MIC) and fractional inhibitory concentration of NaOCl and NO donors were determined. The activation of mammalian targets of rapamycin (mTOR) and ERK and the expression of nitrite reductase and Nrf2 were assessed in HCECs using Western blot analysis. The cysticidal effects of combined NaOCl and NO donors were also evaluated. Results: A dose-dependent toxicity was observed in A. castellanii, HCECs, and keratocytes when treated with NaOCl and SNP. The range of tested NaNO2 concentrations showed no significant toxicity to HCECs; however, dose-dependent toxicity to A. castellanii was observed. The MIC of NaOCl against HCECs and A. castellanii was 8.0 mg/mL. The MIC of NaNO2 and SNP was 500 mM and 10 mM in both HCECs and A. castellanii, respectively. Weak attenuation of the mTOR and ERK phosphorylation was observed and Nrf2 expression decreased slightly after exposure of HCECs to 2.0 mg/mL NaOCl. For the combination treatment, NaOCl (0.125 mg/mL) was selected based on the safety of HCECs and the toxicity of A. castellanii. A more potent anti-Acanthamoeba effect and HCEC toxicity were observed when NaOCl was combined with SNP rather than NaNO2. Conclusions: Combined NaOCl and NO donors had a stronger anti-Acanthamoeba effect compared to either drug alone. Translational Relevance: This study demonstrates that the combined use of various drugs for the treatment of Acanthamoeba infection can enhance the anti-Acanthamoeba effect while minimizing the toxicity of the individual drug.

Effect of Magnetic Microparticles on Cultivated Human Corneal Endothelial Cells.

Purpose: To investigate effects of magnetic microparticles on movement of magnet controlled human corneal endothelial cells (HCECs). Methods: Immortalized HCEC line (B4G12) and primary culture of HCECs were exposed to two commercially available magnetic micro- or nanoparticles, SiMAG (average size 100 nm) and fluidMAG (average size <1000 nm). Cell viability assays and reactive oxygen species production assays were performed. Cellular structural changes, intracellular distribution of microparticles, and expression levels of proteins related to cellular survival were analyzed. Ex vivo human corneas were exposed to microparticles to further evaluate their effects. Magnetic particle-laden HCECs were cultured under the influence of a neodymium magnet. Results: No significant decrease of viability was found in HCECs after exposure to both magnetic particles at concentrations up to 20 µg/mL for 48 hours. However, high concentrations (40 µg/mL and 80 µg/mL) of SiMAG and FluidMAG significantly decreased viability in immortalized HCECs, and only 80 µg/mL of SiMAG and FluidMAG decreased viability in primary HCECs after 48 hours of exposure. There was relative stability of viability at various concentrations of magnetic particles, despite a dose-dependent increase of reactive oxygen species, lactate dehydrogenase, and markers of apoptosis. Ex vivo human cornea study further revealed that exposure to 20 µg/mL of SiMAG and fluidMAG for 72 hours was tolerable. Endocytosed magnetic particles were mainly localized in the cytoplasm. The application of a magnetic field during cell culture successfully demonstrated that magnetic particle-loaded HCECs moved toward the magnet area and that the population density of HCECs was significantly increased. Conclusions: We verified short-term effects of SiMAG and fluidMAG on HCECs and their ability to control movement of HCECs by an external magnetic field. Translational Relevance: A technology of applying magnetic particles to a human corneal endothelial cell culture and controlling the movement of cells to a desired area using a magnetic field could be used to increase cell density during cell culture or improve the localization of corneal endothelial cells injected into the anterior chamber to the back of the cornea.

Advances in ophthalmic drug delivery technology for postoperative management after cataract surgery.

INTRODUCTION: Cataract surgery is becoming more common due to an aging world population. Intraocular lenses and surgical technique have developed remarkably recently, but the development of postoperative medication to prevent postsurgery complications has been relatively delayed. We still largely depend on eye drops for the management of post-cataract-surgery patients. Mental and physical problems that often occur in elderly cataract patients make it difficult for patients to apply eye drops by themselves. It is necessary to develop new effective drug delivery methods. AREAS COVERED: This updated review article provides a brief review of why drug management is needed following cataract surgery and an overview of current developments in new drug delivery methods for ophthalmic treatment. In particular, various novel drug delivery methods that can be used for post-cataract-surgery management and their current development stages are extensively reviewed. EXPERT OPINION: Rapidly developing technologies, such as intraocular and external ophthalmic implants, polymers, and nanotechnology, are being actively applied to develop novel drug delivery systems for safe and effective management after cataract surgery. Their goal is to achieve sufficient drug release for the desired duration with a single application. These will largely replace the inconvenience of eye drops for elderly patients in the future.

Low Contrast Visual Evoked Potentials for Early Detection of Optic Neuritis.

Optic neuritis (ON) detection is important for the early diagnosis and management of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). However, the conventional high-contrast visual evoked potential (VEP) used for ON detection lacks sensitivity for identifying ON presenting as mild or unremarkable visual disturbance, which is common in first-episode ON. Therefore, this study aimed to investigate whether a change in contrast or check size improves the sensitivity of VEP to first-ever ON. In total, 60 patients with the demyelinating disease (29 MS and 31 idiopathic patients with ON) without ON or with first-ever ON at least 6 months prior and 32 healthy controls underwent neuro-ophthalmic evaluations. VEPs were induced using three pattern-reversal checkerboard stimuli having, respectively, 10% contrast with a check size of 32' (LC32 VEP), 100% contrast with a check size of 32' (HC32 VEP; conventional VEP), and 100% contrast with a check size of 16' (HC16 VEP). The receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) were calculated to determine the most appropriate VEP method for detecting optic nerve involvement. The optimal cut-off point was determined using the Youden index (J-index). The McNemar test was used to determine whether dichotomous proportions were equivalent. In comparison with first-ever ON eyes (n = 39) and healthy eyes (n = 64), LC32 VEP showed the highest AUC for discriminating ON (0.750, p < 0.001; 0.730 for HC32 VEP, p < 0.001; 0.702 for HC16 VEP, p = 0.001). In the first-ever ON group, LC32 VEP and conventional HC32 VEP were abnormal in 76.9 and 43.6%, respectively (McNemar, p < 0.001), and combining these tests did not improve sensitivity. These indicate that LC32 VEP is the most sensitive method for detecting first-ever ON. Visual evoked potential with 10% contrast stimuli was superior to conventional VEP for detecting first-ever ON. Thus, adding these LC stimuli might be helpful in identifying optic nerve involvement in ON with mild or unremarkable visual impairment.

Retinal cytotoxicity of silica and titanium dioxide nanoparticles.

The retina plays a key role in human vision. It is composed of cells that are essential for vision signal generation. Thus far, conventional medications have been ineffective for treating retinal diseases because of the intrinsic blood-retinal barrier. Nanoparticles (NPs) are promising effective platforms for ocular drug delivery. However, nanotoxicity in the retinal tissue has not received much attention. This study used R28 cells (a retinal precursor cell line that originated from rats) to investigate the safety of two commonly used types of NPs: silica nanoparticles (SiO2NPs, 100 nm) and titanium dioxide nanoparticles (TiO2NPs, 100 nm). Cellular viability and reactive oxygen species generation were measured after 24, 48, and 72 h of exposure to each NP. Cellular autophagy and the mTOR pathways were evaluated. The retinal toxicity of the NPs was investigated in vivo in rat models. Both types of NPs were found to induce significant dose-dependent toxicity on the R28 cells. A significant elevation of reactive oxygen species generation was also observed. Increased autophagy and decreased mTOR phosphorylation were observed after SiO2NPs and TiO2NPs exposure. The diffuse apoptosis of the retinal cellular layers was detected after intravitreal injection.

Novel Corneal Endothelial Cell Carrier Couples a Biodegradable Polymer and a Mesenchymal Stem Cell-Derived Extracellular Matrix.

Here, we report a transparent, biodegradable, and cell-adhesive carrier that is securely coupled with the extracellular matrix (ECM) for corneal endothelial cell (CEC) transplantation. To fabricate a CEC carrier, poly(lactide-co-caprolactone) (PLCL) solution was poured onto the decellularized ECM (UMDM) derived from in vitro cultured umbilical cord blood-MSCs. Once completely dried, ECM-PLCL was then peeled off from the substrate. It was 20 µm thick, transparent, rich in fibronectin and collagen type IV, and easy to handle. Surface characterizations exhibited that ECM-PLCL was very rough (54.0 ± 4.50 nm) and uniformly covered in high density by ECM and retained a positive surface charge (65.2 ± 57.8 mV), as assessed via atomic force microscopy. Human CECs (B4G12) on the ECM-PLCL showed good cell attachment, with a cell density similar to the normal cornea. They could also maintain a cell phenotype, with nicely formed cell-cell junctions as assessed via ZO-1 and N-cadherin at 14 days. This was in sharp contrast to the CEC behaviors on the FNC-coated PLCL (positive control). A function-related marker, Na+/K+-ATPase, was also identified via western blot and immunofluorescence. In addition, primary rabbit CECs showed a normal shape and they could express structural and functional proteins on the ECM-PLCL. A simulation test confirmed that CECs loaded on the ECM-PLCL were successfully engrafted into the decellularized porcine corneal tissue, with a high engraftment level and cell viability. Moreover, ECM-PLCL transplantation into the anterior chamber of the rabbit eye for 8 weeks proved the maintenance of normal cornea properties. Taken together, this study demonstrates that our ECM-PLCL can be a promising cornea endothelium graft with an excellent ECM microenvironment for CECs.

Moxifloxacin releasing intraocular implant based on a cross-linked hyaluronic acid membrane.

Intraocular antibiotic delivery is an important technique to prevent bacterial infection after ophthalmic surgery, such as cataract surgery. Conventional drug delivery methods, such as antibiotic eye drops, have limitations for intraocular drug delivery due to the intrinsic barrier effect of the cornea. Therefore, frequent instillation of antibiotic eyedrops is necessary to reach a sufficient bactericidal concentration inside the eye. In this study, an intraocular implant, MXF-HA, that combines hyaluronic acid (HA) and moxifloxacin (MXF) was developed to increase the efficiency of intraocular drug delivery after surgery. MXF-HA is manufactured as a thin, transparent, yellow-tinted membrane. When inserted into the eye in a dry state, MXF-HA is naturally hydrated and settles in the eye, and the MXF contained therein is delivered by hydrolysis of the polymer over time. It was confirmed through in vivo experiments that MXF delivery was maintained in the anterior chamber of the eye at a concentration sufficient to inhibit Pseudomonas aeruginosa and Staphylococcus aureus for more than 5 days after implantation. These results suggest that MXF-HA can be utilized as a potential drug delivery method for the prevention and treatment of bacterial infections after ophthalmic surgery.

Visual fatigue induced by watching virtual reality device and the effect of anisometropia.

The effect of small anisometropia on visual fatigue when using virtual reality (VR) devices was investigated. Participants (n = 34) visited three times. In the first visit, VR exposure (10 min) was conducted with the full correction of the refractive error of both eyes. Experimental anisometropia was induced by adding a + 1.0 dioptre spherical lens either on the dominant eyes in the second visit or on the non-dominant eyes in the third visit. At each visit, the participants played a predetermined video game using a head-mounted display VR for 10 min. Visual fatigue was assessed before and after playing VR game using the Virtual Reality Symptom Questionnaire (VRSQ) and high-frequency component of accommodative microfluctuation. Results showed that watching VR induced significant increase of VRSQ score, significant decrease in the maximum accommodation power and objective increase in visual fatigue. Experimental anisometropia induction either on the dominant or non-dominant eyes did not aggravate visual fatigue. Practitioner summary: Mild differences in refractive error (up to 1.0 dioptre) between both eyes do not significantly increase ocular fatigue by viewing virtual reality device (10 min). The impact of small anisometropia may be limited in developing a virtual reality device. Abbreviations: VR: virtual reality; VRSQ: virtual reality symptom questionnaire; HMD: head-mounted display; HFC: high-frequency component.

Nitric oxide attenuated transforming growth factor-ß induced myofibroblast differentiation of human keratocytes.

Nitric oxide (NO) has the potential to modulate myofibroblast differentiation. In this study, we investigated the effect of exogenous NO on the myofibroblast differentiation of human keratocytes using sodium nitrite as a NO donor. Myofibroblasts were induced by exposing resting keratocytes to transforming growth factor (TGF)-ß1. N-cadherin and α-smooth muscle actin (αSMA) were used as myofibroblast markers. Both resting keratocytes and -stimulated keratocytes were exposed to various concentrations of sodium nitrite (1 µM to 1000 mM) for 24 to 72 h. Exposure to sodium nitrite did not alter keratocytes' viability up to a 10 mM concentration for 72 h. However, significant cytotoxicity was observed in higher concentrations of sodium nitrite (over 100 mM). The expression of αSMA and N-cadherin was significantly increased in keratocytes by TGF-ß1 stimulation after 72 h incubation. The addition of sodium nitrite (1 mM) to TGF-ß1-stimulated keratocytes significantly decreased αSMA and N cadherin expression. Smad3 phosphorylation decreased after sodium nitrite (1 mM) exposure in TGF-ß1-stimulated keratocytes. The effect of NO was reversed when NO scavenger, 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) was added in the culture medium. Application of sodium nitrite resulted in significant decrease of corneal opacity when measured at 2 weeks after the chemical burn in the mouse. These results verified the potential therapeutic effect of NO to decrease myofibroblast differentiation of human keratocytes and corneal opacity after injury.

Evaluation of moxifloxacin-induced cytotoxicity on human corneal endothelial cells.

Moxifloxacin hydrochloride (MXF) is widely used for the prevention of bacterial endophthalmitis after intraocular surgeries. However, the safety issue of intracameral injection of MXF for human corneal endothelial cells (HCECs) is still debatable. In this study, we investigated concentration-dependent cytotoxicity (0.05-1 mg/ml) of MXF for immortalized HCECs (B4G12 cell) and the underlying mechanism. Reactive oxygen generation (ROS) and cell viability after MXF exposure was measured. Flow cytometric analysis and TUNEL assay was used to detect apoptotic HCECs after MXF exposure. Ultrastructure of damaged HCECs by MXF was imaged by transmission electron microscope. Western blot analysis and caspase 2, 3 and 8 analysis were used to reveal the underlying mechanism of MXF induced damage in HCECs. We found that MXF induced dose-dependent cytotoxicity in HCECs. MXF exposure increased ROS generation and induced autophagy in HCECs. Increased LDH release represented the cellular membrane damage by MXF. In addition, caspases activation, Bax/Bcl-xL-dependent apoptosis pathway and apoptosis inducing factor nuclear translocation were all involved in MXF induced HCECs' damage, especially after exposure to high dose of MXF (0.5 and 1.0 mg/ml). These findings suggest that MXF toxicity on HCECs should be thoroughly considered by ophthalmologists when intracameral injection of MXF is planned.

Development of a novel hyaluronic acid membrane for the treatment of ocular surface diseases.

Ocular surface diseases (OSD) can cause serious visual deterioration and discomfort. Commercial artificial tear solution containing hyaluronic acid (HA) show excellent biocompatibility and unique viscoelastic characteristics. Here, we developed a novel HA membrane (HAM) by chemical crosslinking using 1,4-butanediol diglycidyl ether for the effective treatment of OSDs. The main purpose of HAMs is to provide sustained release of HA to modulate the wound healing response in OSDs. The safety and efficacy of HAMs were investigated using primary cultured human corneal epithelial cells and various OSD rabbit models. In the dry state, the HAM is firm, transparent, and easy to manipulate. When hydrated, it swells rapidly with high water retention and over 90% transmission of visible light. Human corneal epithelial cells and rabbit eyes showed no toxic response to HAM. Addition of HAMs to the culture medium enhanced human corneal epithelial cell viability and expression of cell proliferation markers. Investigation of HAM wound healing efficacy using mechanical or chemical corneal trauma and conjunctival surgery in rabbits revealed that application of HAMs to the ocular surface enhanced healing of corneal epithelium and reduced corneal limbal vascularization, opacity and conjunctival fibrosis. The therapeutic potential of HAMs in various OSDs was successfully demonstrated.

IgG4-related disease presenting as recurrent scleritis combined with optic neuropathy.

BACKGROUND: We report a case of atypical presentation of IgG4-related disease (IgG4-RD) with recurrent scleritis and optic nerve involvement. CASE PRESENTATION: A 61-year-old male presented with ocular pain and injection in his left eye for 2 months. Ocular examination together with ancillary testing led to the diagnosis of scleritis, which relapsed in spite of several courses of steroid treatment. After cessation of steroid, the patient complained of severe retro-orbital pain and blurred vision. His best corrected vision was count finger, the pupil was mid-dilated and a relative afferent pupillary defect was found. Funduscopic examination demonstrated disc swelling. Magnetic resonance imaging (MRI) showed enhancing soft tissue encasing the left globe, medial rectus muscle and optic nerve. Systemic work-up revealed multiple nodules in right lower lung and a biopsy showed histopathological characteristics of IgG4-RD. Long-term treatment with corticosteroids and a steroid-sparing agent (methotrexate) led to significant improvement in signs and symptoms with no recurrence for 2 years. CONCLUSIONS: This case highlights the significance of IgG4-RD in the differential diagnosis of recurrent scleritis. IgG4-RD may cause optic neuropathy resulting in visual loss. Early diagnosis and proper treatment can prevent irreversible organ damage and devastating visual morbidity.

Effects of Nonporous Silica Nanoparticles on Human Trabecular Meshwork Cells.

PRECIS: Silica nanoparticles (SiNPs), which are potential drug carriers for glaucoma treatment, may induce mild dose-dependent cytotoxicity but not so severe as to compromise a mammalian target of rapamycin (mTOR) pathway in immortalized trabecular meshwork (TM) cells. PURPOSE: Nanoparticle-based ophthalmic drug delivery is a promising field of drug development. In this study, we evaluated the effect of nonporous SiNPs on human TM cells. METHODS: TM cells were exposed to different concentrations (0 to 100 µg/mL) of SiNPs (50, 100, and 150 nm) for up to 48 hours. Transmission electron microscopy confirmed the intracellular distribution of SiNPs. Cellular viability assay, reactive oxygen species generation, autophagy, and activation of the mTOR pathway were evaluated. Histologic analysis of the TM structure was performed after intracameral injection of SiNPs (0.05 mL of 200 µg/mL concentration) in rabbits. RESULTS: SiNPs were taken up by TM cells and localized in the cytoplasm. Neither nuclear entry nor mitochondrial damage was observed. SiNPs induced a mild but dose-dependent increase of lactate dehydrogenase. However, neither increase of intracellular reactive oxygen species levels nor apoptosis was observed after SiNPs exposure. Significant coactivation of autophagy and the mTOR pathway were observed with exposure to SiNPs. Aqueous plexus structure was well maintained without inflammation in rabbits after SiNPs exposure. CONCLUSIONS: SiNPs induce mild and dose-dependent cytotoxicity in TM cells. However, the toxicity level is not enough to compromise the mTOR pathway of TM cells and histologic structure of the aqueous plexus tissue.

Comparison of clinical outcomes after femtosecond laser in situ keratomileusis in eyes with low or high myopia.

AIM: To compare the clinical results of femtosecond (FS) laser in situ keratomileusis (LASIK) in high myopic patients and low myopic patients. METHODS: This study included 212 myopic eyes undergoing LASIK using a VisuMax 500kHz FS laser. All treated eyes were assigned to one of two groups according to preoperative manifest spherical refraction: low myopia group (A, >-4.0 D) and high myopia group (B, ≤-4.0 D). Uncorrected and corrected distance visual acuity (UDVA, CDVA), refractive errors, and higher-order aberrations (HOAs) were measured preoperatively and 1wk, 1, 3 and 6mo postoperatively. RESULTS: At 6mo of follow-up, 92% and 76% had a UDVA of 20/20 or better in group A and B, respectively (P=0.037) and UDVA was significantly different between two groups (P=0.042). Six and seven percentage lost one line of CDVA in group A and B, respectively (P=0.572) and no eyes in both groups lost more than two lines. Each group had 87% and 76% of treated eyes within ±0.5 D of the intended correction (P=0.186), and 13% and 43% with a change of >0.50 D in spherical equivalent from 1wk to 6mo postoperatively (P=0.005). In terms of postoperative astigmatism, each group had 89.1% and 76.6% within ±0.50 D, respectively and there was significant difference (P=0.006). Group A tends to induce smaller HOAs than group B. CONCLUSION: FS LASIK is effective and safe for correcting high myopia as well as low myopia. However, high myopic eyes showed more postoperative astigmatism and HOAs which affect visual acuity.

Changes in Collagen Structure and Permeability of Rat and Human Sclera After Crosslinking.

Purpose: To use second harmonic generation imaging and fluorescence recovery after photobleaching to demonstrate alterations in scleral collagen structure and permeability after crosslinking in rat and human eyes. Methods: Excised rat and human scleras were imaged ex vivo with an inverted two-photon excitation fluorescence microscope before and after photochemical crosslinking using riboflavin and 405-nm laser light. Fluorescence recovery after photobleaching was applied to measure the diffusion of fluorescein isothiocyanate-dextran across the sclera. Results: Crosslinking caused scleral collagen fibers to become wavier and more densely packed, with surface collagen being more affected than deeper collagen fibers. Crosslinked sclera showed significantly decreased permeability in the irradiation zone and also extended as far as 250 µm outside the irradiation zone. Conclusions: Photochemical crosslinking induced changes in scleral structure and permeability that extended to tissue even outside the irradiation zone. Translational Relevance: Ultrastructural changes associated with the emerging clinical technique of photochemical scleral crosslinking have not been well characterized. We demonstrate not only changes in scleral collagen by second harmonic generation imaging but also the associated functional changes in tissue permeability by fluorescence recovery after photobleaching. We report the novel finding of reduced permeability extending well beyond the direct irradiation zone. This has implications for control in the clinical setting.

A case of severe flare reaction observed in HLA B27 associated acute anterior uveitis.

BACKGROUND: Anterior chamber flare reaction refers to the light reflection from the protein in aqueous humor. We report a case of very severe flare reaction observed in human leukocyte antigen (HLA)- B27 associated acute anterior uveitis (AAU). CASE PRESENTATION: An age 43 male patient visited the uveitis clinic complaining of decreased visual acuity in the right eye which developed 1 week before. The detailed ophthalmic examination revealed very severe flare reaction in the anterior chamber with diffuse conjunctival hyperemia in the right eye. Pupil margin and iris details were barely observable. Oral prednisolone 20 mg daily with topical 1% prednisolone acetate (Pred Forte, Allergan, CA) every 2 h and 1% topical cyclopentolate (Cyclogyl, Alcon, TX) three times daily were immediately prescribed. The next day, the flare reaction of the right eye decreased significantly and inflammatory cells in the anterior chamber were visible. Detailed fundus examination revealed no inflammatory signs on the retina and ciliary body. Later, the blood test revealed positive HLA B27 and autoantibodies against lupus anticoagulant with mild elevation of C reactive protein. There were no signs for ankylosing spondylitis. Continued treatment and tapering of topical 1% prednisolone acetate for 4 weeks led to the complete resolution of the anterior uveitis. CONCLUSIONS: We experienced HLA-B27 AAU with the feature of a very severe flare reaction. Conventional uveitis treatment was successful to acquire the complete resolution of the inflammation.