Spectral-domain optical coherence tomography of peripheral lattice degeneration of myopic eyes before and after laser photocoagulation.

PURPOSE: To investigate the microstructural characteristics of lattice degenerations before and after laser photocoagulation in myopic eyes by spectral-domain optical coherence tomography (SD-OCT). METHODS: Twenty-five eyes of 25 consecutive patients at the High Myopia Clinic of the National Taiwan University Hospital were retrospectively reviewed. Myopic eyes with peripheral lattice degeneration were enrolled in the study. Best-corrected visual acuity (BCVA), axial length measurement, color fundus photography was performed. SD-OCT analyses on the lattice degeneration were performed before and after prophylactic laser photocoagulation. All patients were followed for at least 6 months. RESULTS: In total, 25 myopic eyes with peripheral lattice degenerations were studied. The mean refractive error was -9.92 ± 4.77 Diopters (D) with 21 (84%) of the eye being highly myopic (Over -6.0 D). The average axial length was 27.7 ± 1.86 mm. In these myopic eyes, retinal thinning was the most common finding (92%), followed by vitreoretinal traction (72%), retinoschisis (44%), vitreous membrane with deposits (36%), and retinal break with subretinal fluid (4%). A blunting effect of the vitreoretinal tractions was found after laser photocoagulation. CONCLUSION: To our knowledge we firstly investigated the pre- and post-laser photocoagulation microstructural changes using SD-OCT. It demonstrated a beneficial effect of retinoplasty, which released vitreoretinal tractions after laser photocoagulation. Combined with the findings of subtle microstructural retinal breaks and subretinal fluid, early prophylactic laser treatment warrants sincere consideration in these myopic eyes.

Multimodal imaging of linear lesions in the fundus of pathologic myopic eyes with macular lesions.

PURPOSE: To detect, using multimodal imaging, lacquer cracks (LCs) and myopic stretch lines (MSLs) in pathologic myopic eyes with macular hemorrhage (MHE) and those without. METHODS: We collected 18 consecutive pathologic myopic eyes (spherical equivalent ≤ -8.0 diopters) that had presented with linear, yellowish-white lesions in the macula. We categorized the eyes into either the MHE group or the non-MHE group. All underwent fluorescein angiography (FA), near infrared autofluorescence (NIA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD-OCT). RESULTS: In all 18 eyes, the linear lesions were hyperfluorescent under NIA imaging, but hypofluorescent under ICGA. All ten eyes in the MHE group had LCs, and two had both LCs and MSLs. None of the eight eyes in the non-MHE group had LCs. Regarding proximity to the MHE, LCs tended to locate closer than MSLs. Incidental perforating scleral vessels were clearly visible on the tracked SD-OCT scanning line, joining the choroid beneath the border of MHE. Sample cases are illustrated using delicate photographs and explanations. CONCLUSION: NIA imaging combined with SD-OCT and ICGA can detect and differentiate early the subtle difference between the two types of linear lesions in pathological myopic eyes. Notably, MSLs were not associated with MHEs or LCs in our consecutive series.

History and development of ophthalmology in Taiwan.

Western medicine was first introduced to Taiwan by medical missionaries in the mid-19th century. Modernization of medicine was systematically transplanted to Taiwan in the Japanese colonial period, and ophthalmology was established third among hospital departments, following internal medicine and surgery. Dr Hidetaka Yamaguchi, an ophthalmologist, was the first head of the Taihoku Hospital, later known as National Taiwan University Hospital (NTUH; Taipei, Taiwan). Ophthalmologists during the colonial period conducted studies on tropical and infectious eye diseases. After World War II, ophthalmologists at NTUH played an important role in medical education, residency training, studies, and teaching. Dr Yan-Fei Yang established the Taiwan Ophthalmological Society in 1960 and instituted its official journal in 1962. Dr Ho-Ming Lin established the Department of Ophthalmology at the Tri-Service General Hospital in the 1950s and the Veterans General Hospital in the 1960s. Taiwan ophthalmologists eradicated trachoma by 1971. Cataract surgery and penetrating keratoplasty were initially performed in the 1960s. Currently, there are about 1600 ophthalmologists in Taiwan conducting an estimated 120,000 cataract surgeries and 600 corneal transplantations annually. Many subspecialty societies have been established recently that serve to educate Taiwanese ophthalmologists and to connect with international ophthalmic societies. Taiwan ophthalmologists continue to contribute to the advancement of ophthalmic knowledge globally.

Macular retinal detachment associated with intrachoroidal cavitation in myopic patients.

PURPOSE: To investigate the clinical characteristics and treatment outcomes of macular retinal detachment (MRD) associated with intrachoroidal cavitation (ICC) in myopic patients. METHODS: In this retrospective, consecutive, interventional case series, five patients with ICC and associated MRD were enrolled from January 2005 to December 2012. Basic ocular characteristics and clinical appearances of their ICC and MRD were recorded. Individual treatment courses were assessed with fundus photographs and serial optical coherence tomography. RESULTS: The average age and refraction were 43.8 ± 11.0 years old and -9.37 ± 2.73 diopters, respectively. Initial BCVA ranged from 20/100 to 20/30. Definite communication between the ICC and the subretinal space was noted in one case, suspected curvilinear communication in two cases, and between the peripapillary area and the subretinal space in two cases. Two cases received intravitreal injection of perfluoropropane and peripapillary laser; subretinal fluid (SRF) resolved in one and decreased in the other. One case had SRF reabsorbed after prolonged use of topical carbonic anhydrase inhibitor. CONCLUSIONS: ICC in high myopic patients may be associated with MRD. There might be communication between the ICC and the subretinal space. Intravitreal injection of an expansile gas may be beneficial, but the best treatment remains undetermined.

Focal foveal atrophy of unknown etiology: clinical pictures and possible underlying causes.

BACKGROUND/PURPOSE: Focal foveal atrophy is defined as the presence of a small, focal, ill-defined, hypopigmented foveal or juxtafoveal lesion, with the remaining retina unaffected. The purpose of this study was to report the clinical characteristics and optical coherence tomography (OCT) in patients with focal foveal atrophy of unknown etiology. METHODS: The study was a retrospective observational case series. Data collected included complete ocular examination results for best corrected visual acuity (BCVA), ophthalmoscopy, fundus photography, fluorescein angiography, color sense discrimination tests, visual field tests, and OCT examinations. RESULTS: Twenty-three eyes in 21 patients were examined. The mean patient age was 49.2 ± 15.4 years. The mean BCVA was 20/25. The 21 patients were divided into three groups according to OCT results. Group 1 eyes (n = 10) had intact inner and outer hyperreflective layers (HRLs), with the signal of the inner HRL corresponding to the junction between the inner and outer photoreceptor segments and the outer HRL corresponding to the retinal pigment epithelium (RPE). Group 2 eyes (n = 9) had small hyporeflective defects with defects in the inner HRL at the fovea but an intact outer HRL. Group 3 eyes (n = 4) had small hyporeflective defects in both the inner and outer HRLs at the fovea. Groups 3 eyes had significantly lower visual acuity compared to Group 1 eyes and Group 2 eyes. There was no significant difference in visual acuity between Group 1 and Group 2 eyes. There were no significant differences among the groups with respect to color vision or foveal thickness. CONCLUSION: This is the first report of clinical presentations for patients with focal foveal atrophy of unknown etiology. OCT aided in the diagnosis and assessment of the degree of retinal structural abnormalities, but the real etiology of foveal atrophy remains unclear.

Foveola nonpeeling internal limiting membrane surgery to prevent inner retinal damages in early stage 2 idiopathic macula hole.

PURPOSE: The purpose of this study was to investigate and present the results of a new vitrectomy technique to preserve the foveolar internal limiting membrane (ILM) during ILM peeling in early stage 2 macular holes (MH). METHODS: The medical records of 28 consecutive patients (28 eyes) with early stage 2 MH were retrospectively reviewed and randomly divided into two groups by the extent of ILM peeing. Group 1: foveolar ILM nonpeeling group (14 eyes), and group 2: total peeling of foveal ILM group (14 eyes). A donut-shaped ILM was peeled off, leaving a 400-µm-diameter ILM over foveola in group 1. RESULTS: Smooth and symmetric umbo foveolar contour was restored without inner retinal dimpling in all eyes in group 1, but not in group 2. The final vision was better in group 1 (P = 0.011). All eyes in group 1 (100 %) and seven of 14 eyes in group 2 (50 %)regained the inner segment/outer segment (IS/OS) line. Restoration of the umbo light reflex was found in 12 of 14 eyes in group 1 (86 %) but none in group 2 (0 %). CONCLUSIONS: Nonpeeling of the foveolar ILM in early stage 2 idiopathic MH surgery prevented inner retinal damages, restored umbo light reflex, achieved better foveolar microstructures, and led to better final visual acuity.

Long-term outcome of foveolar internal limiting membrane nonpeeling for myopic traction maculopathy.

PURPOSE: To investigate the long-term results of a novel technique to preserve the foveolar cone without peeling off the foveolar internal limiting membrane (ILM) during myopic traction maculopathy surgery. METHODS: Nineteen patients (19 eyes) were retrospectively studied and divided into 2 groups by the extent of ILM peeled and followed for more than 3 years. Group 1: foveolar ILM nonpeeling group (FN) (12 eyes) and Group 2: total peeling of foveal ILM group (TP) (7 eyes). A donut-shaped ILM was peeled off, leaving a 400-µm diameter ILM over foveola with a sharp margin in FN group. RESULTS: Macular hole was developed in 2 of the 7 eyes (28.6%) in the TP group and none in the FN group. Long-term central fovea thickness thinning and decrease of vision were found in the TP group, but not in the FN group (P < 0.05). Inner segment/outer segment line recovered in 75% of the 12 eyes in the FN group, but in only 14.3% of the 7 eyes in the TP group. CONCLUSION: Preservation of the foveolar cone by foveola nonpeeling surgery correlates with better anatomical and visual results than total peel, prevents long-term foveolar retinal thinning, and successfully saves the fovea from macular hole formation.

Transplantation of induced pluripotent stem cells without C-Myc attenuates retinal ischemia and reperfusion injury in rats.

Induced pluripotent stem cells (iPSC) are novel stem cell populations, but the role of iPSC in retinal ischemia and reperfusion (I/R) injury remains unknown. Since oncogene c-Myc is substantially contributed to tumor formation, in this study, we investigated the effects, mechanisms and safety of subretinal transplantation of iPSC without c-Myc (non-c-Myc iPSC) in a rat model of retinal I/R injury. Retinal I/R injury was induced by raising the intraocular pressure of Sprague-Dawley rats to 110 mmHg for 60 min. A subretinal injection of non-c-Myc iPSC or murine epidermal fibroblast was given 2 h after I/R injury. Electroretinograms (ERG) were performed to determine the functionality of the retinas. The surviving retinal ganglion cells (RGCs) and retinal apoptosis following I/R injury were determined by counting NeuN-positive cells in whole-mounted retinas and TUNEL staining, respectively. The generation of reactive oxygen species (ROS) and the activities of superoxide dismutase (SOD) and catalase (CAT) in the retinal tissues were determined by lucigenin- and luminol-enhanced chemiluminescence and enzyme-linked immunosorbent assay (ELISA). The degree of retinal oxidative damage was assessed by nitrotyrosine, acrolein, and 8-hydroxy-2'-deoxyguanosine (8-OHdG) staining. The expression of brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF) and basic fibroblast growth factor (bFGF) in retinas was measured by immunohistochemistry and ELISA. We found that subretinal transplantation of non-c-Myc iPSC significantly suppressed the I/R-induced reduction in the ERG a- and b-wave ratio, attenuated I/R-induced loss of RGCs and remarkably ameliorated retinal morphological changes. Non-c-Myc iPSC potentially increased the activities of SOD and CAT, decreased the levels of ROS, which may account for preventing retinal cells from apoptotic cell death. In addition, the levels of BDNF and CNTF in retina were significantly elevated in non-c-Myc iPSC-treated eyes. Track the non-c-Myc iPSC after transplantation, most transplanted cells are remained in the subretinal space, with spare cells express neurofilament M markers at day 28. Six months after transplantation in I/R injured rats, no tumor formation was seen in non-c-Myc iPSC graft. In conclusion, non-c-Myc iPSC effectively rescued I/R-induced retinal damages and diminished tumorigenicity. Non-c-Myc iPSC transplantation attenuated retinal I/R injury, possibly via a mechanism involving the regulation of oxidative parameters and paracrinal secretion of trophic factors.

Surgical treatment of lamellar macular hole secondary to epiretinal membrane.

BACKGROUND: To examine the surgical results of lamellar macular hole (LMH) secondary to epiretinal membrane (ERM). METHODS: A 3-year retrospective review was performed of patients with LMH secondary to ERM that underwent ERM and internal limiting membrane (ILM) peeling. The main outcome measures included best-corrected visual acuity (BCVA) and postoperative macular structure. The results were compared with cases of idiopathic ERM with similar baseline demographic characteristics. RESULTS: Thirty eyes in 30 patients were collected. The mean BCVA improvement was 3.4 Snellen lines after a mean follow-up period of 16.9 months. Optical coherence tomography (OCT) showed improved macular contour in 27 cases. Patients with intravitreal gas tamponade exhibited a higher percentage of restoration of macular contour than those without (P = 0.016). Final BCVA was correlated with an intact photoreceptor inner segment-outer segment (IS-OS) junction (P = 0.03). The degree of visual improvement is less than that observed in idiopathic ERM patients. CONCLUSION: In LMH secondary to ERM with significant visual decrease, ERM and ILM peeling may improve BCVA. Postoperative gas tamponade is associated with better restoration of macular configuration. Final BCVA is related to an intact photoreceptor IS-OS junction rather than to the normalization of the macular contour.

Clinical characteristics and visual function tests with retinal tomographic correlation in patients with Stargardt's disease in Taiwan.

BACKGROUND/PURPOSE: Stargardt's disease is the most common form of juvenile macular dystrophy. The purpose of this study is to report the clinical characteristics, visual function, and retinal tomography of patients diagnosed with Stargardt's disease in Taiwan. METHODS: Retrospective case series; data collected include results of complete ophthalmic examinations: best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, fluorescein angiography, color sense discrimination test, electroculography (EOG), electroretinography (ERG), dark adaptation, visual field test, and optical coherence tomography (OCT) examinations focused on the macular area. RESULTS: Twenty patients were enrolled in this study. The mean age of the patients was 32.1 years. The mean logMAR-converted visual acuity of all patients was 0.96. Maculopathy with or without flecks was evident in all patients. Fluorescein angiography revealed hyperfluorescence in the macula of all cases. Varying degrees of color sense discrimination dysfunction were noted. Electrophysiologic studies showed subnormal to abnormal responses in most patients. Decreased foveal thickness was evident on OCT and foveal thickness was inversely associated with logMAR visual acuity. Also, logMAR visual acuity was associated with total error scores on the color sense discrimination test and the Arden ratio of EOG. The Arden ratio of EOG correlated with the thickness of the outer ring of the macula. CONCLUSION: Typical clinical presentations of Stargardt's disease were demonstrated in our case series. OCT findings showed a correlation between foveal thickness and visual acuity, making OCT a useful predictor for other visual function tests. Our results indicate that OCT is helpful in the evaluation of visual acuity and the progression of maculopathy in patients with Stargardt's disease.

Characteristics and treatment response of polypoidal choroidal vasculopathy in highly myopic eyes.

BACKGROUND: To compare the characteristics and treatment responses of polypoidal choroidal vasculopathy (PCV) between highly myopic and non-highly myopic eyes. METHODS: This retrospective cohort study included patients diagnosed with PCV at the clinic of National Taiwan University Hospital between 2013 and 2019. The diseased eyes were grouped per refractive error and axial length at diagnosis. Imaging data were used to retrieve the PCV characteristics, and electronic medical records were used to retrieve the treatment responses. RESULTS: Among 116 eyes with PCV, 11 eyes of 10 patients were highly myopic; seven of these patients were women. All highly myopic eyes showed a thin subfoveal choroid, while three eyes had a pachychoroid phenotype with significant focal choroidal thickening. After treatment with either intravitreal anti-vascular endothelial growth factor (VEGF) injections, photodynamic therapy (PDT), or both, best-corrected visual acuity was better in the high-myopia group at 1 year. Visual acuity at presentation and the presence of feeder vessels were found to be predictors of the visual outcome. CONCLUSIONS: In this study we reported, to the best of our knowledge, the largest cohort of PCV in highly myopic eyes to date. Female predominance, lower incidence of subretinal haemorrhage, and a thin choroid with a focal pachychoroid phenotype were found to characterise PCV in highly myopic eyes. Visual acuity transiently improved after either anti-VEGF monotherapy or combination therapy with PDT.

Comparison of Refractive Outcomes in Patients with Highly Myopic Versus Non-highly Myopic Eyes Undergoing Phacovitrectomy.

INTRODUCTION: Combined phacovitrectomy is gaining popularity due to efficiency and immediate visual improvement. However, concerns regarding erroneous intraocular lens (IOL) calculation in combination surgery are increasing, such as myopic shift owing to a thick macula and consequent underestimation of the axial length. Therefore, this study aimed to compare the refractive outcomes of combined phacovitrectomy in patients with highly myopic and non-highly myopic eyes. METHODS: A retrospective chart review was performed on patients who received combined phacoemulsification, intraocular lens implantation, and small gauge pars plana vitrectomy for cataract and macular pathologies in highly myopic and non-highly myopic eyes. Pre- and postoperative evaluation and ocular parameters were recorded, and analyses were performed using the Student's t test and regression analysis. RESULTS: A total of 133 patients with macular pathologies, including myopic tractional maculopathy, macular hole, and epiretinal membrane, were enrolled. SRK II or SRK/T models were used for calculating IOL. The mean absolute error of refraction change was 0.65 D; 83.5% of patients were within 1-D error, 57.9% within 0.5-D error, and 35.3% within 0.25-D error, with SRK/T showing better precision and yielding more myopic shift. Furthermore, the predictive accuracy of SRK II or SRK/T was better in patients with non-highly myopic eyes. Moreover, Barrett's universal II formula was not superior to SRK II or SRK/T in the prediction of postoperative refractive error (p = 0.48). CONCLUSION: Refractive outcomes were satisfactory in the cohort of patients with highly myopic eyes. The combined implementation of SRK II and SRK/T was not inferior to Barrett's universal II formula in predicting satisfactory refractive outcomes. Combination surgery can be an option for patients with both cataract and macular pathologies.

Correlation of Visual Acuity and Outer Retinal Thickness in Myopic Atrophic Maculopathy: A Retrospective Review.

INTRODUCTION: Myopic atrophic maculopathy is prevalent among patients with pathologic myopia and frequently leads to relentless vision loss. Several grading systems were established to facilitate the understanding of myopic atrophic maculopathy. However, the anatomical details in different stages of myopic maculopathy are so far not clearly elucidated. This study aims to investigate the visual acuity and retinal sublayer features in highly myopic eyes with varying severities of myopic atrophic maculopathy (MAM). METHODS: The clinical records of 111 consecutive patients (158 eyes) with high myopia (refractive error ≤ -6.0 D and axial length ≥ 26.0 mm) were reviewed. Fundus photography, optical coherence tomography (OCT), and best-corrected visual acuity (BCVA) were measured. MAM was graded according to the META-analysis for Pathologic Myopia (META-PM) classification system. Myopic choroidal neovascularization (mCNV) and dome-shaped macula (DSM) were also investigated. RESULTS: Among the 158 eyes, 18 (11%), 21(13%), 24 (15%), 25 (16%), 23 (15%), and 24 (15%) had tessellated fundus, diffuse chorioretinal atrophy, diffuse chorioretinal atrophy with DSM, patchy atrophy, patchy atrophy with DSM, and MAM with mCNV, respectively. A total of 23 (15%) eyes had macular atrophy without mCNV. Progressive thinning in the Henle's fiber and outer nuclear layers, myoid and ellipsoid zone (MEZ), outer segment (OS), and interdigitation zone and retinal pigmented epithelium based on the severity of MAM (p-value < 0.001) was found. MEZ and OS were most significantly reduced in thickness (p-value < 0.001). The presence of mCNV demonstrated significant outer retinal layer thinning compared with that of the tessellated fundus (p-value = 0.031). Patchy atrophy with DSM showed statistically poorer BCVA compared with that without (p-value = 0.008). CONCLUSION: Visual acuity and outer retinal sublayer characteristics were correlated with the severity of MAM. Outer retinal sublayer analysis by spectrum-domain OCT shed some light on the mechanisms of MAM progression.

Elevation of angiogenic factor Cysteine-rich 61 levels in vitreous of patients with proliferative diabetic retinopathy.

PURPOSE: Cysteine-rich 61 (Cyr61) is one of the angiogenic factors involved in proliferative diabetic retinopathy (PDR). To further investigate its role, we measure and compare the vitreous levels of Cyr61 and vascular endothelial growth factor in patients with PDR and to localize Cyr61 expression in associated proliferative epiretinal membranes. METHODS: Vitreous obtained from 56 patients with active PDR, 16 patients with active PDR pretreated with bevacizumab, 19 patients with quiescent PDR, 15 non-PDR patients with diabetic macular edema, and 25 patients with non-diabetic-related eye diseases were subjected to enzyme-linked immunosorbent assay for Cyr61 and vascular endothelial growth factor levels. Epiretinal membranes from 18 patients were stained immunohistochemically for Cyr61. RESULTS: Vitreous Cyr61 levels were significantly higher in active PDR patients, quiescent PDR patients, and diabetic macular edema patients compared with non-diabetic control patients (P < 0.01). Pretreatment of bevacizumab significantly suppressed vitreous vascular endothelial growth factor levels; however, it did not inhibit vitreous Cyr61 levels in active PDR patients. Cysteine-rich 61 was strongly detected in endothelial cells and myofibroblasts within active PDR membranes but not in idiopathic epiretinal membrane. CONCLUSION: Vitreous Cyr61 levels were related to different states of PDR and correlated with vascular endothelial growth factor levels in PDR patients. Pretreatment of bevacizumab did not inhibit vitreous Cyr61 levels in active PDR patients. Cysteine-rich 61 might mediate angiogenesis and post-angiogenic fibrosis in PDR.

Macular thickness and aging in retinitis pigmentosa.

PURPOSE: This study was designed to analyze macular tomography in patients of different ages with retinitis pigmentosa (RP) and correlate their visual function with macular thickness, which was measured by optical coherence tomography. METHODS: In all, 75 RP patients and 75 controls were stratified into three age groups and macular thickness was measured by optical coherence tomography. The tomography was subdivided into three circular zones, four quadrants, and nine areas for analysis. Ophthalmic examinations, which involved ophthalmoscopic examinations, dark adaptation tests, visual acuities, visual field examinations, electrooculography, and color sense discrimination tests, were performed. RESULTS: Macular thickness of the RP patients decreased in the middle age group (45- to 55-year old), whereas the oldest group showed an increased thickness. The thickness of the outer inferior area remained virtually unchanged, whereas the thickness of the inner temporal area showed the most fluctuation with age. In terms of circular sections, the most dramatic changes in macular thickness were observed in the fovea, and the aging effect decreased outward to the outer ring. Furthermore, the thickness of the fovea was more important than the thickness of the inner ring and the outer ring for electrooculography, visual acuity, and color sense discrimination in RP patients. CONCLUSIONS: In middle age RP patients, the macular thickness decreased, whereas an increased thickness was observed in patients older than 55 years. In addition, the inner temporal area was the most fragile, and the outer inferior area was the least affected in patients with RP.

Examining rhodopsin retention in endoplasmic reticulum and intracellular localization in vitro and in vivo by using truncated rhodopsin fragments.

More than 100 mutations of rhodopsin have been identified to be associated with retinitis pigmentosa (RP), and mostly autosomal-dominant RP (ADRP). The majority of rhodopsin-associated ADRP is caused by protein misfolding and ER retention. In this study, we aimed to evaluate rhodopsin folding, exiting the ER and intracellular localization through expression of the rhodopsin fragments in COS-1 cells as well as in the transgenic zebrafish. We cloned human rhodopsin cDNA, which was then divided into the N-terminal domain, the C-terminal domain, and the fragment between the N- and C-terminal domains, and examine their intracellular expression in vitro and in vivo. We introduced a point mutation, either F45L or G51V, into this fragment and observed the intracellular localization of these mutants in COS-1 cells and in the zebrafish. The results revealed all of the truncated rhodopsin fragments except for the C-terminal domain and the full-length rhodopsin which had some plasma membrane localization, formed aggregates nearby or within the ER in COS-1 cells; however, the N-terminally truncated rhodopsin fragment, the C-terminal domain, and the full-length rhodopsin could traffic to the ROS in the zebrafish. Besides, the F45L mutation and the G51Vmutation in the rhodopsin fragment between the N- and C-terminal domains produced different effects on the aggresome formation and the intracellular distribution of the mutants both in vivo and in vitro. This current study provides new information about the mutant rhodopsin as well as in treatment of the RP in humans in the future.

Biomarkers in the pathogenesis of epiretinal membrane and myopic traction maculopathy: Effects of internal limiting membrane incompliance and posterior staphyloma.

BACKGROUND: This study compared the structural and vascular intraretinal changes between epiretinal membrane and myopic traction maculopathy eyes. METHODS: An observational retrospective study of treatment-naïve epiretinal membrane and myopic traction maculopathy eyes was conducted to identify biomarkers of a 3 × 3 mm macular region centered on the fovea, using optical coherence tomography angiography. RESULTS: The myopic traction maculopathy and epiretinal membrane groups comprised 27 and 32 eyes, respectively. In the myopic traction maculopathy group, the spherical equivalent was more myopic and the axial length was longer than in the epiretinal membrane group. Myopic traction maculopathy eyes had larger outer and smaller inner retinal volumes, larger area and perimeter of foveal avascular zones, greater circularity of foveal avascular zones, and smaller foveal vessel density in the superficial layer than epiretinal membrane eyes. Internal limiting membrane incompliance and staphyloma were significantly more in the myopic traction maculopathy group than in the epiretinal membrane group. CONCLUSIONS: The intraretinal changes in myopic traction maculopathy eyes compared with epiretinal membrane eyes showed larger avascular zones, which may have been caused by tangential internal limiting membrane incompliance. Anteroposterior traction forces from staphyloma in myopic traction maculopathy eyes may lead to larger outer retinal volumes. In epiretinal membrane eyes, traction forces confined to the superficial retina caused large inner retinal volumes and foveal acircularity.

Clinical Characteristics of Highly Myopic Patients With Asymmetric Myopic Atrophic Maculopathy-Analysis Using Multimodal Imaging.

Purpose: To evaluate the factors associated with asymmetric myopic atrophic maculopathy (MAM) in highly myopic patients. Methods: We enrolled highly myopic patients with asymmetric MAM according to the atrophy, traction, and neovascularization (ATN) classification. The results of color fundus photography, optical coherence tomography (OCT), OCT angiography, and corneal visualization Scheimpflug technology (Corvis ST tonometry) were reviewed. The association between inter-eye differences in clinical features and MAM grading was analyzed using logistic regression analysis. Results: Among the 72 eyes of 36 patients 61.0 ± 9.3 years of age, 9, 33, 17, and 13 eyes had A1, A2, A3, and A4, respectively. The mean axial length was 30.44 ± 1.92 mm, and there was no significant difference between eyes with less severe and more severe MAM. The inter-eye differences in MAM grading were associated with the inter-eye differences in the presence of Bruch's membrane defects (P = 0.014), ellipsoid zone disruption (P = 0.013), vessel density of the deep retinal layer (P = 0.022), foveal avascular zone circularity (P = 0.012), foveal avascular zone area (P = 0.049), flow area of the choriocapillaris (P = 0.013), vessel diameter (P = 0.045), and fractal dimension (P = 0.015). No Corvis ST parameter was statistically significant. A higher difference in the choriocapillaris flow area (P = 0.013; adjusted odds ratio = 1.10 [1.02-1.18]) remained associated with higher inter-eye differences in MAM grading in the multivariable regression. Conclusions: A smaller choriocapillaris flow area was associated with more severe MAM, suggesting that vascular factors play pivotal roles in MAM.

Regulation of Cyr61/CCN1 expression by hypoxia through cooperation of c-Jun/AP-1 and HIF-1α in retinal vascular endothelial cells.

Hypoxia is the most important factor in the pathogenesis of diabetic retinopathy. Cysteine-rich 61 (Cyr61) is one of the angiogenic factors involved in the development of proliferative diabetic retinopathy (PDR). The aim of this study was to investigate the mechanism of hypoxia-induced Cyr61 expression in retinal vascular endothelial cells. The hypoxia-induced expression of mRNA and protein of Cyr61 was studied in monkey choroidal retinal vascular endothelial (RF/6A) cells. Luciferase reporter assays and electrophoretic mobility shift assays were used to identify the hypoxia responsible region and transcription factors in the Cyr61 promoter. Chromatin immunoprecipitation and immunoprecipitation were performed to study the role of hypoxia-inducible factor (HIF)-1α and c-Jun/activator protein-1 (AP-1) in Cyr61 transcriptional regulation. The results showed that hypoxia significantly induced Cyr61 mRNA and protein expression in RF/6A cells. The effect was mediated through phosphorylation of c-Jun. Luciferase assays, electrophoretic mobility shift assays, chromatin immunoprecipitation and immunoprecipitation showed that HIF-1α interacted with c-Jun/AP-1 and their binding on the AP-1 binding motif within the Cyr61 promoter induced the expression of Cyr61. In conclusion, hypoxia controlled the transcriptional regulation of the Cyr61 gene in RF/6A cells by cooperation of HIF-1α and c-Jun/AP-1. Cyr61 might play an important role in ischemic retinal diseases, such as PDR.

Expressions of lymphotactin and its receptor, XCR, in Lewis rats with experimental autoimmune anterior uveitis.

BACKGROUND: To demonstrate the expression of lymphotactin and its receptor (XCR) in the iris/ciliary body and popliteal lymph node, and to clarify their roles in experimental autoimmune anterior uveitis (EAAU). METHODS: Uveitis was induced in Lewis rats by injection of melanin-associated antigen into the peritoneum and footpad. At defined time points, mRNA expression levels of lymphotactin and XCR in the iris/ciliary body and popliteal lymph node were measured by semiquantitative polymerase chain reaction. Lymphotactin levels in aqueous humor and serum after immunization were determined by enzyme-linked immunosorbent assay. In a separate experiment, an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC; 200 mg/kg/day), was injected daily into the intraperitoneum after immunization. Cellular sources of lymphotactin were determined by immunhistochemical staining and flow cytometry. RESULTS: Lymphotactin mRNA was upregulated in the iris/ciliary body with a peak level at day 14, which is in line with the disease course. XCR mRNA was expressed maximally and then declined gradually from days 5 to 21. With an expression pattern similar to that of mRNA expression, lymphotactin in aqueous humor had attracted corresponding numbers of leukocytes. PDTC markedly inhibited the expression of lymphotactin in aqueous humor and serum. Immunohistochemical staining and flow cytometry analysis revealed that the expression of lymphotactin was detected in infiltrated inflammatory cells, dominantly CD8+ T cells, and increased along with inflammation. CONCLUSIONS: The lymphotactin and XCR interaction might direct distinct lymphocytes subsets to inflammatory sites. Lymphotactin could regulate the inflammatory process. Lymphotactin expression may be modulated, at least in part, through the NF-κB signaling pathway.