Tai-Chi Lin

CT of Globe Rupture: Analysis and Frequency of Findings

OBJECTIVE The objective of our study was to evaluate the CT characteristics of globe rupture. MATERIALS AND METHODS The medical records of patients seen in the emergency department with blunt, penetrating, or explosive orbit injury were retrospectively reviewed. A total of 75 patients (76 injured globes) were included (56 males and 19 females; average age, 45.1 years; age range, 5-95 years). CT examinations were reviewed by two experienced radiologists without knowledge of ophthalmologic findings, original orbital CT images, or surgical outcomes. RESULTS Of the 76 globe injuries, 33 (43%) were ruptured and 43 (57%) were nonruptured. There were significant differences between the ruptured and nonruptured globes with respect to intraocular hemorrhage, lens dislocation and destruction, an intraocular foreign body, intraocular gas, anterior chamber depth (ACD), and globe deformity and wall irregularity (p < 0.05). There was good interrater agreement between the two radiologists (kappa value range, 0.63-0.96). The average sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of CT for the detection of globe rupture based on readings by two radiologists were 76%, 85%, 80%, 82%, and 81%, respectively. CONCLUSION Although CT is extremely useful in the evaluation of ocular trauma, it should not be solely relied on for the diagnosis of globe rupture because of the potentially catastrophic consequences of an undiagnosed injury. A difference in ACD can be diagnostic of globe rupture.

Corneal neovascularization and contemporary antiangiogenic therapeutics.

Abstract Corneal neovascularization (NV), the excessive ingrowth of blood vessels from conjunctiva into the cornea, is a common sequela of disease insult that can lead to visual impairment. Clinically, topical steroid, argon laser photocoagulation, and subconjunctival injection of bevacizumab have been used to treat corneal NV. Sometimes, the therapies are ineffective, especially when the vessels are large. Large vessels are difficult to occlude and easily recanalized. Scientists and physicians are now dedicated to overcoming this problem. In this article, we briefly introduce the pathogenesis of corneal NV, and then highlight the existing animal models used in corneal NV research—the alkali‐induced model and the suture‐induced model. Most of all, we review the potential therapeutic targets (i.e., vascular endothelial growth factor and platelet‐derived growth factor) and their corresponding inhibitors, as well as the immunosuppressants that have been discovered in recent years by corneal NV studies.

Correlation between microRNA-34a levels and lens opacity severity in age-related cataracts

PurposeMicroRNA 34a (miR-34a) is involved in regulating tissue senescence. However, the role of miR-34a in age-related cataracts is unclear. In this study, we evaluated the correlations among the severity of lens opacity, patient age, and miR-34a expression level in the lens epithelium of age-related cataracts for clarifying the role of miR-34a in the lens senescence.MethodsThis study was carried as a case control study in the Department of Ophthalmology, Taipei Veterans General Hospital, Taiwan. We recorded age of each patient at the time of their cataract surgery and information regarding lens opacity according to a modified version of the Lens Opacities Classification System III. Correlations among age, lens opacity, and miR-34a expression levels were evaluated.ResultsThis study evaluated 110 patients with a mean age of 73.19 years (SD±10.2). Older patients had higher nuclear cataract (NC), cortical (C), and posterior subcapsular cataract (P) scores (one-way analysis of variance (ANOVA), P<0.05). miR-34a expression levels were significantly different between each age group (ANOVA post hoc Bonferroni’s test, P<0.001), and there were moderate correlations between high NC, C, and P cataract scores and high miR-34a levels (Pearson correlation coefficient; R=0.606, 0.575, and 0.515, respectively).ConclusionsThe current study demonstrated positive correlations between high miR-34a levels and high lens opacity severity in NC, C, or P cataracts. These results suggest that miR-34a expression has a role in lens senescence.

Using induced pluripotent stem cell-derived conditional medium to attenuate the light-induced photodamaged retina of rats

Background Light injury to photoreceptor cells and retinal pigment epithelium may lead to oxidative stress and irreversible degeneration of retina, especially degeneration of the high energy‐demanded macula. The model of retinal photodamage could be applied to age‐related macular degeneration and other degenerative retinal diseases for exploring new treatments. Based on broadly investigated induced pluripotent stem cells (iPSC) in the field of retinal degeneration, we aimed to clarify further how the interaction progresses between iPSC‐conditional medium (CM) and light‐damaged retina. Methods iPSCs were generated from murine embryonic fibroblasts of C57/B6 mice by retroviral transfection of three factors: Oct4, Sox2, and Klf4. Cytokine array was performed to analyze the components of CM. Sprague–Dawley rats receiving white light exposure to retina were viewed as an animal model of light injury. The rats were divided into four subgroups: light‐injured rats receiving intravitreal injection of iPSC‐CM, apoptotic iPSC‐CM, or sodium phosphate buffer (PBS); and a control group without light damage. The electroretinography and thickness of outer nuclear layer were measured to document the therapeutic effects in each condition. Apoptosis arrays for detecting annexin V and caspase 3 were performed in the retinal tissues from each group. Results Murine embryonic fibroblasts were induced into iPSCs and expressed the marker genes similar to embryonic stem cells. These iPSCs can differentiate into Embryoid bodies (EBs), three germ layers in vitro and develop teratoma in severe combined immunodeficiency mice. The quantitative polymerase chain reaction of our iPSC‐CM showed significantly elevated fibroblast growth factor‐2, glial cell‐derived neurotrophic factor, and insulin‐like growth factor‐binding proteins‐1, ‐2, and ‐3. Compared to rats without photodamage, the light‐injured rats receiving iPSC‐CM had less reduction of outer nuclear layer thickness on Day 21 than other groups treated with either PBS or apoptotic iPSC‐CM. In the same animal model, both a‐ and b‐waves of electroretinography measurement in the group treated with iPSC‐CM were significantly maintained compared to the control group and others with apoptotic iPSC‐CM or PBS treatment. The apoptosis assay also demonstrated lower levels of annexin V and caspase 3 in the group with iPSC‐CM treatment than in other groups presenting increasing apoptotic markers. Conclusion The conditional medium of iPSCs contains plenty of cytoprotective, immune‐modulative and rescue chemicals, contributing to the maintenance of neuronal function and retinal layers in light‐damaged retina compared with apoptotic iPSC‐CM and PBS. The antiapoptotic effect of iPSC‐CM also shows promise in restoring damaged neurons. This result demonstrates that iPSC‐CM may serve as an alternative to cell therapy alone to treat retinal light damage and maintain functional and structural integrity of the retina.

Retinal stem cells and potential cell transplantation treatments

&NA; The retina, histologically composed of ten delicate layers, is responsible for light perception and relaying electrochemical signals to the secondary neurons and visual cortex. Retinal disease is one of the leading clinical causes of severe vision loss, including age‐related macular degeneration, Stargardts disease, and retinitis pigmentosa. As a result of the discovery of various somatic stem cells, advances in exploring the identities of embryonic stem cells, and the development of induced pluripotent stem cells, cell transplantation treatment for retinal diseases is currently attracting much attention. The sources of stem cells for retinal regeneration include endogenous retinal stem cells (e.g., neuronal stem cells, Müller cells, and retinal stem cells from the ciliary marginal zone) and exogenous stem cells (e.g., bone mesenchymal stem cells, adipose‐derived stem cells, embryonic stem cells, and induced pluripotent stem cells). The success of cell transplantation treatment depends mainly on the cell source, the timing of cell harvesting, the protocol of cell induction/transplantation, and the microenvironment of the recipients retina. This review summarizes the different sources of stem cells for regeneration treatment in retinal diseases and surveys the more recent achievements in animal studies and clinical trials. Future directions and challenges in stem cell transplantation are also discussed.

Stem Cell Therapy for Corneal Regeneration Medicine and Contemporary Nanomedicine for Corneal Disorders.

The ocular surface is the outermost part of the visual system that faces many extrinsic or intrinsic threats, such as chemical burn, infectious pathogens, thermal injury, Stevens–Johnson syndrome, ocular pemphegoid, and other autoimmune diseases. The cornea plays an important role in conducting light into the eyes and protecting intraocular structures. Several ocular surface diseases will lead to the neovascularization or conjunctivalization of corneal epithelium, leaving opacified optical media. It is believed that some corneal limbal cells may present stem cell-like properties and are capable of regenerating corneal epithelium. Therefore, cultivation of limbal cells and reconstruction of the ocular surface with these limbal cell grafts have attracted tremendous interest in the past few years. Currently, stem cells are found to potentiate regenerative medicine by their capability of differentiation into multiple lineage cells. Among these, the most common cell sources for clinical use are embryonic, adult, and induced stem cells. Different stem cells have varied specific advantages and limitations for in vivo and in vitro expansion. Other than ocular surface diseases, culture and transplantation of corneal endothelial cells is another major issue for corneal decompensation and awaits further studies to find out comprehensive solutions dealing with nonregenerative corneal endothelium. Recently, studies of in vitro endothelium culture and ρ-associated kinase (ROCK) inhibitor have gained encouraging results. Some clinical trials have already been finished and achieved remarkable vision recovery. Finally, nanotechnology has shown great improvement in ocular drug delivery systems during the past two decades. Strategies to reconstruct the ocular surface could combine with nanoparticles to facilitate wound healing, drug delivery, and even neovascularization inhibition. In this review article, we summarized the major advances of corneal limbal stem cells, limbal stem cell deficiency, corneal endothelial cell culture/transplantation, and application of nanotechnology on ocular surface reconstruction. We also illustrated potential applications of current knowledge for the future treatment of ocular surface diseases.

Laminin modification subretinal bio-scaffold remodels retinal pigment epithelium-driven microenvironment in vitro and in vivo.

Advanced age-related macular degeneration (AMD) may lead to geographic atrophy or fibrovascular scar at macular, dysfunctional retinal microenvironment, and cause profound visual loss. Recent clinical trials have implied the potential application of pluripotent cell-differentiated retinal pigment epithelial cells (dRPEs) and membranous scaffolds implantation in repairing the degenerated retina in AMD. However, the efficacy of implanted membrane in immobilization and supporting the viability and functions of dRPEs, as well as maintaining the retinal microenvironment is still unclear. Herein we generated a biomimetic scaffold mimicking subretinal Bruchs basement from plasma modified polydimethylsiloxane (PDMS) sheet with laminin coating (PDMS-PmL), and investigated its potential functions to provide a subretinal environment for dRPE-monolayer grown on it. Firstly, compared to non-modified PDMS, PDMS-PmL enhanced the attachment, proliferation, polarization, and maturation of dRPEs. Second, PDMS-PmL increased the polarized tight junction, PEDF secretion, melanosome pigment deposit, and phagocytotic-ability of dRPEs. Third, PDMS-PmL was able to carry a dRPEs/photoreceptor-precursors multilayer retina tissue. Finally, the in vivo subretinal implantation of PDMS-PmL in porcine eyes showed well-biocompatibility up to 2-year follow-up. Notably, multifocal ERGs at 2-year follow-up revealed well preservation of macular function in PDMS-PmL, but not PDMS, transplanted porcine eyes. Trophic PEDF secretion of macular retina in PDMS-PmL group was also maintained to preserve retinal microenvironment in PDMS-PmL eyes at 2 year. Taken together, these data indicated that PDMS-PmL is able to sustain the physiological morphology and functions of polarized RPE monolayer, suggesting its potential of rescuing macular degeneration in vivo.

Retinal prostheses in degenerative retinal diseases.

Abstract Degenerative retinal diseases may lead to significant loss of vision. Age‐related macular degeneration (AMD) and retinitis pigmentosa (RP), which eventually affect the photoreceptors, are the two most common retinal degenerative diseases. Once the photoreceptorcells are lost, there are no known effective therapies for AMD or RP. The concept of retinal prosthesis is to elicit neural activity in the remaining retinal neurons by detecting light and converting it into electrical stimuli using artificial devices. Subretinal, epiretinal, and other retinal prostheses implants are currently designed to restore functional vision in retinal degenerative diseases. In this review, we have summarized different types of retinal prostheses, implant locations, and visual outcomes. Our discussions will further elucidate the results from clinical trials, and the challenges that will need to be overcome to more efficaciously assist patients with AMD and RP in the future.

Optical coherence tomography in spontaneous resolution of vitreomacular traction syndrome.

Vitreomacular traction syndrome (VTS) is a vitreoretinal interface abnormality. The disorder is caused by incomplete posterior vitreous detachment with persistent traction on the macula that produces symptoms and decreased vision. Most symptomatic eyes with VTS undergo a further decrease in visual acuity. Spontaneous complete vitreomacular separation occurs infrequently in eyes with VTS. Surgical intervention may be considered if severe metamorphopsia and decreased visual quality occur. Herein, we report 2 typical cases of idiopathic VTS with spontaneous resolution of vitreo-retinal traction demonstrated by optical coherence tomography. Optical coherence tomography is a sensitive and useful tool for the confirmation of diagnosis and for the serial anatomical evaluation of patients with VTS.

Visual prognosis of massive submacular hemorrhage in polypoidal choroidal vasculopathy with or without combination treatment.

Background Submacular hemorrhage associated with polypoidal choroidal vasculopathy (PCV) may cause severe visual loss. The purpose of this study is to report the visual prognosis of massive submacular hemorrhage in patients with PCV. Methods Twenty patients with PCV and submacular hemorrhage who received either subretinal tissue plasminogen activator (TPA) with vitrectomy or intravitreal injection of TPA and gas to achieve pneumatic displacement of the hemorrhage were enrolled. Additionally, combination treatment with either photodynamic therapy (PDT) or intravitreal injection of vascular endothelial growth factor inhibitors (anti‐VEGF) was performed to treat the underlying PCV. Results Five patients received subretinal TPA with vitrectomy and 15 patients received intravitreal injection of TPA and gas to remove or displace the submacular hemorrhage. Combination treatment with PDT and intravitreal anti‐VEGF was performed in three patients and intravitreal anti‐VEGF injection alone in 13 patients. The mean logarithm of the minimal angle of resolution converted from the best corrected visual acuity (BCVA) were improved at 3 months, 6 months, and 12 months. Better initial BCVA, smaller size of submacular hemorrhage and younger age were statistically significant predictors for BCVA. Combination treatment with PDT showed significant efficacy in the improvement of BCVA. Conclusion Combination treatment of submacular hemorrhage secondary to PCV may yield visual and anatomic improvements. Initial BCVA, the initial size of submacular hemorrhage and age were significant predictors for visual prognosis.