Comparative Evaluation of Visual Outcomes in Combined Cataract and Vitrectomy for Idiopathic Epiretinal Membrane with an Advanced or Conventional Intraocular Lens.

INTRODUCTION: The aim of this study was to investigate the efficacy of new monofocal intraocular lens (IOL) in comparison with conventional monofocal IOL in patients undergoing combined cataract and vitrectomy surgery for epiretinal membrane (ERM). METHODS: This prospective non-randomized comparative study included 65 eyes of 65 patients who underwent combined cataract and vitrectomy for ERM with implantation of advanced monofocal IOL (Eyhance ICB00, 33 patients) and standard monofocal IOL (Tecnis ZCB00, 32 patients). Monocular visual acuities were measured 6 months post-operatively, including corrected and uncorrected distance visual acuity (CDVA, UCDVA), uncorrected intermediate visual acuity (UCIVA), and uncorrected near visual acuity (UCNVA). Furthermore, contrast sensitivity and metamorphopsia were measured. RESULTS: There was no significant difference between two groups regarding operation time, post-operative CDVA, UCDVA, UCNVA, and spherical equivalent (p > 0.05). Monocular UCIVA was significantly higher in the Eyhance IOL group than in the Tecnis IOL group (p = 0.005). The photopic and mesopic contrast sensitivities were comparable between each group for any spatial frequency (p > 0.05). The correlation coefficients from correlations between retinal wrinkling ratio and M score did not differ significantly between groups (p = 0.877), and the degree of metamorphopsia was not significantly related to the type of IOL (p = 0.969). CONCLUSIONS: In combined cataract and vitrectomy for ERM, Eyhance IOL provided significant better visual performance at intermediate distance than standard monofocal IOL without compromising operation time, distance vision, contrast sensitivity, and evaluating metamorphopsia. Eyhance IOL can be a useful option for both surgeons and patients.

Short-term Efficacy and Safety of Intravitreal Brolucizumab Injection for Treatment-Naive Exudate Age-related Macular Degeneration: A Multicenter Study.

PURPOSE: To compare short-term efficacy and safety of intravitreal brolucizumab injection with aflibercept in treatment-naive neovascular age-related macular degeneration (nAMD) patients. METHODS: A total of 59 eyes from 59 treatment-naive nAMD patients in three hospitals were retrospectively reviewed. Of which, 27 patients underwent intravitreal brolucizumab injections and 32 received aflibercept. After monthly consecutive three injections, best-corrected visual acuity (BCVA; in logarithm of minimal angle of resolution [logMAR]), central macular thickness (CMT), dry macula achievement rate, and intraocular inflammation (IOI) incidence were compared. RESULTS: After loading-phase treatment, BCVA was significantly increased from 0.48 ± 0.30 logMAR at baseline to 0.33 ± 0.21 logMAR at 3 months in the brolucizumab group (p = 0.002) and 0.40 ± 0.39 logMAR at baseline to 0.33 ± 0.36 logMAR at 3 months in the aflibercept group (p = 0.007). But there was no significant difference in BCVA improvement at 3 months between the two groups. CMT significantly decreased from 429.67 ± 250.59 µm at baseline to 210.67 ± 93.53 µm at 3 months in the brolucizumab group and from 346.69 ± 159.09 µm to 234.52 ± 83.42 µm in the aflibercept group (both p < 0.001). The amount of CMT reduction was significantly greater in the brolucizumab group after 3 months (p = 0.036). In typical AMD eyes, brolucizumab showed similar BCVA improvement but better CMT reduction at 3 months (p = 0.018). Dry macula achievement rate was not significantly different between the two groups. One IOI was observed in the brolucizumab group. CONCLUSIONS: Intravitreal injections of brolucizumab and aflibercept showed similar anatomical and functional outcomes. But CMT reduction was greater in the brolucizumab group. One IOI was identified, which was tolerable for topical agents. These results suggest that brolucizumab could be a novel first line treatment option for treating naive nAMD patients.

In Vivo Electroporation Improves Retinal Delivery of Intravitreally Injected Exosomes.

Purpose: Mesenchymal stem cell (MSC)-derived exosomes are promising therapeutic agents and natural nanoscale delivery platforms for treating degenerative retinal diseases. This study investigated the effect of electroporation on the retinal delivery of intravitreally administered MSC-derived exosomes in a murine model. Methods: Exosomes isolated from adipose tissue-derived MSCs were stained with ExoGlow exosome-specific dye and administered to the right eyes of 40 Sprague-Dawley rats. Electroporation was performed in 20 rats immediately after intravitreal injection (electroporation group); 5 square pulses of 40 V/cm for 50 ms each with 950-ms intervals were administered. The remaining 20 rats were assigned to the no-electroporation group. The eyeballs were harvested 24 h later for evaluation. The total number of fluorescent particles per hyperfield was counted from the retinal flat mounts to quantify the retinal delivery of exosomes. Tissue damage after electroporation was evaluated using retinal histological sections and a terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end labeling (TUNEL) assay. Results: A significantly higher number of fluorescent particles per hyperfield were observed in the retinal flat mounts of the electroporation group compared with that in the no-electroporation group (599.0 ± 307.5 vs. 376.9 ± 175.4; P = 0.013). Retinal histological sections and TUNEL assays showed no signs of tissue damage after electroporation. Conclusions: In vivo electroporation can improve the retinal delivery of intravitreally injected exosomes.

Evaluation of a New Monofocal Intraocular Lens in Patients Undergoing Cataract and Vitrectomy Surgery for Idiopathic Macular Hole.

PURPOSE: To evaluate the usefulness of a newly generated monofocal intraocular lens (IOL) in patients who underwent combined cataract and pars plana vitrectomy (PPV) surgery for idiopathic macular hole (MH). METHODS: A prospective study was conducted on 89 eyes of 89 patients who underwent combined cataract and PPV surgery for MH. The patients were divided into two groups: Eyhance ICB00 and Tecnis ZCB00. Pre-operative characteristics, post-operative visual outcomes, contrast sensitivity, and complications were compared between the two groups. A univariate regression analysis was performed to identify the factors that may affect the postoperative visual outcomes. RESULTS: Both groups showed significant improvement in mean corrected distance visual acuity (CDVA) six months post-operation (p < 0.001). There was no significant difference in pre-operative characteristics or complications between the two groups. However, the Eyhance ICB00 group showed a significantly higher uncorrected intermediate visual acuity (UCIVA) value at 6 months after surgery than the Tecnis ZCB00 group (p = 0.014). Contrast sensitivity values were not significantly different between the two groups. The univariate regression analysis revealed a significant correlation between preoperative CDVA and minimum linear diameter of MH with postoperative UCIVA in the Eyhance ICB00 group. CONCLUSIONS: The newly generated Eyhance ICB00 IOL showed promising results in terms of post-operative UCIVA, with no significant difference in complications or contrast sensitivity values compared to the Tecnis ZCB00 IOL. These findings suggest that the Eyhance ICB00 IOL may be a useful option for patients who undergo combined cataract and PPV surgery for idiopathic MH, particularly for those who require intermediate visual acuity.

The Relationship between Rainfall Pattern and Epilithic Diatoms in Four Streams of Central-Western Korea for Three Years (2013-2015).

To study the effect of rainfall patterns on diatom communities in four major central western streams on the Korean Peninsula during the monsoon seasons of 2013 through 2015, we measured precipitation, environmental factors, and epilithic diatoms at 42 sites before (May) and after (August and September) each monsoon. The Mangyeonggang river and Sapgyocheon stream (SS) had a high percentage of low-permeability soil, and the stream had the highest proportion (49.1%) of surrounding land in urban areas. Precipitation and precipitation frequency was closely correlated with electrical conductivity and nutrients, and this was particularly evident in SS. Epilithic diatom abundance for the most abundant species as, Navicula minima, decreased in the stream in 2013 and 2014 and increased in 2015 when precipitation and precipitation frequency were low. This was not clearly distinguishable in the ecological characteristics of each watercourse's indicator species, except in SS. The dynamic community index was highest in 2015 (ca. 5.50), and the annual changes in the index were clearly shown in SS. The precipitation pattern and the dynamic community index were negatively correlated (r = -0.026~-0.385), and the precipitation within 2 weeks (r = -0.480 for SS) before the second sampling and the frequency of 10 mm of precipitation were closely correlated in the stream (r = -0.450 for SS). The distribution of epilithic diatoms in the four watercourses is therefore affected by monsoon precipitation and precipitation frequency, and the dynamic community index is determined by soil characteristics and land use.

Multifocal Electroretinography Changes over 12 Months after Resolution of Central Serous Chorioretinopathy: Prospective Observational Study.

INTRODUCTION: This prospective observational study aimed to evaluate the changes in retinal function after the anatomical resolution of central serous chorioretinopathy by multifocal electroretinography. METHODS: Thirty-two eyes of 32 patients with unilaterally resolved central serous chorioretinopathy were prospectively studied. Serial multifocal electroretinography examinations were performed at the initial visit for active central serous chorioretinopathy, the time of anatomical resolution (resolved central serous chorioretinopathy), and 3, 6, and 12 months after resolution. The peak amplitudes of the first kernel responses were analysed and compared with those in 27 age-matched normal controls. RESULTS: Compared with controls, the N1 amplitudes of rings 1-4 and P1 amplitudes of rings 1-3 showed statistically significant reductions at 12 months after the resolution of central serous chorioretinopathy (p < 0.05). The multifocal electroretinography amplitude substantially increased at the time of resolution and gradually improved until 3 months after the resolution of central serous chorioretinopathy. CONCLUSION: Serial examinations with multifocal electroretinography showed that retinal responses increased mostly after the resolution of central serous chorioretinopathy, and this improvement slowly progressed until 3 months; however, the multifocal electroretinography amplitudes remained statistically reduced 12 months after the anatomical resolution of central serous chorioretinopathy, indicating the residual functional deficits detected by multifocal electroretinography.

Vogt-Koyanagi-Harada syndrome-like uveitis after nivolumab administration as a treatment for ovarian cancer.

PURPOSE: To report a case of Vogt-Koyanagi-Harada (VKH) syndrome-like posterior uveitis after nivolumab administration to treat an ovarian cancer with an electrophysiological finding. A 61-year-old woman with ovarian cancer (stage 3A) and salpingo-oophorectomy surgery history visited the clinic complaining of blurred vision in both eyes. She had been enrolled a clinical trial using nivolumab in patients with ovarian cancer. She received four cycles of nivolumab administration and experienced blurred vision one week before the initial visit. There was no remarkable finding in the anterior segment and the vitreous body. Multiple subretinal fluid accumulations and serous retinal detachment were identified on the posterior pole. Subretinal fluid with choroidal folding was noted in optical coherence tomography, and multiple leakage points were also observed in wide-field fundus fluorescein angiography. Therefore, intravenous high-dose steroid pulse therapy was applied under the diagnosis of VKH syndrome-like posterior uveitis induced by an immunotherapy agent. After steroid therapy, the subretinal fluid was absorbed completely, and the patient's visual acuity was recovered to the normal range. The amplitudes in the multifocal electroretinogram were also restored after the treatment. CONCLUSION: Nivolumab is a human IgG4 monoclonal antibody and an immune checkpoint inhibitor. It is associated with the upregulation of T-cell activity by interfering with the interaction between the programmed death-1 (PD-1) receptor and the PD-ligand. Targeted therapy using immunotherapy agents has been widely used for malignant melanoma, lung cancer, renal cell carcinoma, and other cancers. However, immunotherapy agents such as nivolumab can induce autoimmune-related adverse events including uveitis. This report suggests that VKH syndrome-like posterior uveitis could be induced by nivolumab administration for an ovarian cancer treatment, which was resolved by steroid pulse therapy.

Birth-related retinal hemorrhages: The Soonchunhyang University Cheonan Hospital universal newborn eye screening (SUCH-NES) study.

PURPOSE: To report the prevalence, related factors, and characteristics of birth-related retinal hemorrhages (RHs) according to their severity in healthy newborns using a telemedicine network and wide-field digital retinal imaging (WFDRI). METHODS: Newborns who underwent WFDRI at 61 obstetrics/gynecology hospitals between January 2017 and December 2019 were enrolled. Demographics and related factors were compared among newborns with and without RHs. The newborns' eyes were divided into the minimal, mild, moderate, and severe groups according to the number of RHs, and characteristics like bilaterality, laterality, involved retinal layer, involved zone, macular and/or optic nerve (ON) involvement were compared. RESULTS: Among 56247 newborns, 13026 had birth-related RHs (23.2%). Normal spontaneous vaginal delivery (NSVD) showed the highest association with RHs (odds ratio, 19.774; 95% confidence interval, 18.277-21.393; P < 0.001) on multivariate analysis. Bilateral RHs (8414/13026; 64.59%) were more common than unilateral RHs (4612/13026; 35.41%); however, unilateral RHs (2383/4217; 56.51%) were more common than bilateral RHs (1834/4217; 43.49%) in the minimal group. RHs showed no laterality differences between the two eyes (P = 0.493). Most RHs were intraretinal (18678/21440; 87.12%), and 2328 (31.65%) eyes with preretinal hemorrhage were observed in the severe group. Zone I RHs were common in the minimal (7072/7090; 99.75%), mild (4953/4960; 99.86%), and moderate (2013/2035; 98.92%) groups; zone I and II RHs were common in the severe group (4843/7355; 65.85%); and RHs in zone III were rare (7/21440; 0.03%). Most RHs showed no macular and/or ON involvement in the minimal and mild group; however, this was common in the severe group (7111/7355; 96.68%). CONCLUSIONS: Birth-related RHs were common in healthy newborns and were significantly associated with NSVD. RHs were usually bilateral, intraretinal, and distributed posterior to the retina, but severe RHs had unique characteristics. Future long-term and longitudinal studies are required to elucidate the prognosis of severe RHs.

Prediction of Geosmin at Different Depths of Lake Using Machine Learning Techniques.

Geosmin is a major concern in the management of water sources worldwide. Thus, we predicted concentration categories of geosmin at three different depths of lakes (i.e., surface, middle, and bottom), and analyzed relationships between geosmin concentration and factors such as phytoplankton abundance and environmental variables. Data were collected monthly from three major lakes (Uiam, Cheongpyeong, and Paldang lakes) in Korea from May 2014 to December 2015. Before predicting geosmin concentration, we categorized it into four groups based on the boxplot method, and multivariate adaptive regression splines, classification and regression trees, and random forest (RF) were applied to identify the most appropriate modelling to predict geosmin concentration. Overall, using environmental variables was more accurate than using phytoplankton abundance to predict the four categories of geosmin concentration based on AUC and accuracy in all three models as well as each layer. The RF model had the highest predictive power among the three SDMs. When predicting geosmin in the three water layers, the relative importance of environmental variables and phytoplankton abundance in the sensitivity analysis was different for each layer. Water temperature and abundance of Cyanophyceae were the most important factors for predicting geosmin concentration categories in the surface layer, whereas total abundance of phytoplankton exhibited relatively higher importance in the bottom layer.

Surgical Outcomes of Vitrectomy for Macular Hole-induced Retinal Detachment According To Various Surgical Methods: A Multicenter Retrospective Study.

PURPOSE: To investigate the surgical outcomes of vitrectomy for macular hole-induced retinal detachment(MHRD), with respect to the surgical adjunctive method used. METHOD: We performed retrospective multicenter study of patients who underwent vitrectomy for MHRD. The visual/anatomical outcomes after vitrectomy were analyzed. We also analyzed these outcomes according to surgical method and the presence of persistent macular hole after the vitrectomy. RESULT: Thirty-four patients (34 eyes) from 6 hospitals were included in this study. The mean age of the patients was 64.56 ± 12.23 years; 31 patients (91.2%) were female. The mean LogMAR best-corrected visual acuity (BCVA) significantly improved 6 months after vitrectomy (p < .001). Retinal detachment completely improved in 32 eyes (94.1%). The visual prognoses and macular hole closure rates were not different depending on subretinal fluid drainage site. The presence or absence of a persistent macular hole after vitrectomy did not affect the visual outcomes. However, the recurrence of MHRD was significantly higher in eyes with persistent macular holes(p = .015). CONCLUSION: The surgeries to treat MHRD differed in terms of the procedure depending on the surgeons, but the visual outcomes did not differ depending on the surgical adjunctive method employed. There were no differences in the visual prognoses, regardless of whether there was a persistent macular hole; however, recurrence was significantly higher in eyes with persistent macular holes. Therefore, further surgical treatment might be considered for eyes with persistent macular holes after MHRD surgery.

Correlations among metamorphopsia test scores, optical coherence tomography findings and multifocal electroretinogram responses in epiretinal membrane patients.

PURPOSE: To quantify metamorphopsia with a novel objective method in patients with epiretinal membrane (ERM) and to compare the relationships among metamorphopsia scores, spectral-domain optical coherence tomography (OCT) findings, and multifocal electroretinogram (mfERG) results. METHODS: This study included 52 eyes of 52 patients with idiopathic ERM who underwent comprehensive ophthalmologic examinations, including measurement of best-corrected visual acuity (BCVA), OCT, and mfERG. The degree of metamorphopsia was quantified using MonPack One® (Metrovision, Perenchies, France). On the topographic map of the early treatment diabetic retinopathy (ETDRS) grid, retinal thickness in the central, superior, inferior, nasal, and temporal subfields were measured, and metamorphopsia scores for each corresponding subfield were also obtained. The amplitudes and implicit times of mERG were elicited from each subfield. Then, the correlations among metamorphopsia scores, OCT findings, and mfERG responses were analyzed. RESULTS: The mean age of the patients was 65.3 ± 18.5 y, and the average metamorphopsia score of the individual subfields was 2.03 ± 1.18. Initial BCVA was 0.50 ± 0.12 logMAR, but there was no significant correlation between metamorphopsia scores and BCVA. The metamorphopsia scores from the central subfields showed significant correlations with central retinal thickness (CRT) (p = 0.001). The mean metamorphopsia scores in the central subfield showed a significant relationship with the mean N1 and P1 amplitudes (p = 0.001, p = 0.048, respectively), while no relationship was observed between metamorphopsia scores and mfERG amplitudes in other subfields. CONCLUSIONS: The degree of metamorphopsia in patients with ERM could be objectively quantified in each subfield using a novel metamorphopsia test. The metamorphopsia scores were significantly correlated with retinal thickness, especially at the central subfields, and the scores in the central subfields were significantly correlated with the N1 and P1 amplitudes of mfERG. Thus, the metamorphopsia test can be a useful method to evaluate metamorphopsia symptoms for patients with ERM.

Swept-source optical coherence tomography angiography findings of diabetic papillopathy after intravitreal bevacizumab.

PURPOSE: We report a case of diabetic papillopathy (DP) treated with intravitreal bevacizumab injections and evaluated for disc vessel changes using swept-source optical coherence tomography angiography (SS-OCTA). OBSERVATIONS: A 52-year-old man was referred with a 1-week history of acute painless decreased vision in both eyes (OU). His best-corrected visual acuity (BCVA) was 20/40 in the right eye (OD) and 20/100 in the left eye (OS). Fundus examination showed swollen optic discs with superficial radially oriented telangiectatic vessels, peripapillary splinter hemorrhages, and hard exudates OU. On SS-OCTA, B-scan images displayed blood flow signals in the thickened retinal nerve fiber layer (RNFL) of the optic disc and superficial RNFL slab images displayed radially oriented telangiectatic vessels OU. Laboratory tests revealed previously unknown diabetes, and we diagnosed the patient with DP OU. Two weeks after an intravitreal injection of bevacizumab OS, the disc swelling, radially oriented telangiectatic vessels, and peripapillary splinter hemorrhages had decreased OS. The superficial RNFL slab OS also depicted decreased radially oriented telangiectatic vessels. However, OD showed no interval changes. Two weeks after an intravitreal bevacizumab injection OD, improved BCVA, decreased disc swelling, radially oriented telangiectatic vessels, and peripapillary splinter hemorrhages were observed OU. The superficial RNFL slab also showed decreased radially oriented telangiectatic vessels OU. CONCLUSIONS AND IMPORTANCE: This case showed that bevacizumab is a useful treatment option for DP as they resolve underlying optic nerve capillary vasculopathy. SS-OCTA demonstrated resolved superficial telangiectatic vessels of the optic disc which has not been previously described.

A RANDOMIZED PAIRED-EYE TRIAL OF INTRAVITREAL DEXAMETHASONE IMPLANT FOR CYSTOID MACULAR EDEMA IN RETINITIS PIGMENTOSA.

PURPOSE: To evaluate the efficacy and safety of intravitreal dexamethasone (DEX) implant in retinitis pigmentosa patients with cystoid macular edema (CME). METHODS: In this randomized, noncontrolled, paired-eye, single crossover clinical trial, one eye of retinitis pigmentosa patients with bilateral CME with central macular thickness of >250 µm was randomized to intravitreal DEX implant while the fellow eye was observed. Both eyes were started on topical dorzolamide. At Month 6, DEX implant was eligible for both eyes when CME was >250 µm. Patients were followed up until Month 12. Primary outcome measures were the central macular thickness and best-corrected visual acuity changes from baseline at Month 2. RESULTS: Fourteen patients with bilateral RP-CME were included. Study eyes showed significant central macular thickness decrease (median, -147.5 µm; P = 0.001) and best-corrected visual acuity improvement (median, +6 letters; P = 0.001) at Month 2, but not at Month 6. Intravitreal DEX implant at Month 6 produced comparable efficacy to baseline treatment in 11 fellow eyes and 12 study eyes. Topical dorzolamide did not show significant therapeutic efficacy. During 12 months, elevated intraocular pressure of >21 mmHg and cataract progression were observed in 14.3% and 40.0% of study eyes. CONCLUSION: Intravitreal DEX implant can both reduce macular thickness and improve vision in RP-CME, while repeated injection is required.

Benthic Diatom Communities in Korean Estuaries: Species Appearances in Relation to Environmental Variables.

In the Korean Peninsula's southern estuaries, the distributive characteristics of epilithic diatoms and the important environmental factors predicting species occurrence were examined. The collection of diatoms and measurements of water quality and land-use were performed every May between 2009 and 2016, with no influence from the Asian monsoon and snow. Throughout the study, 564 diatoms were classified with first and second dominant species of Nitzschia inconspicua and N. perminuta. Based on diatom appearance and standing crops, the 512 sampling stations were divided into four groups by cluster analysis, and two regions, namely the West and East Sea. Geographically, G1, G2, G3, and G4 were located in the East Sea, Southeast Sea, West Sea, and Southwest Sea, respectively. Canonical correspondence analysis (CCA) results indicated that environmental factors, such as turbidity, electric conductivity (EC), and total phosphorus (TP), significantly influenced the distribution of epilithic diatoms. A random forest model showed that major environmental factors influencing the diatom species appearance included EC, salinity, turbidity, and total nitrogen. This study demonstrated that the spatial distribution of epilithic diatoms in the southern estuaries of the Korean Peninsula was determined by several factors, including a geographically higher tidal current-driven turbidity increase and higher industrial or anthropogenic nutrient-loading.

The retinal pigment epithelial response after retinal laser photocoagulation in diabetic mice.

To investigate the characteristics of regenerated retinal pigment epithelial (RPE) cells after retinal laser photocoagulation in diabetic mice. C57BL/6J mice were used to induce diabetes using intraperitoneal injection of streptozotocin. The proliferation of RPE cells after laser photocoagulation was determined using the 5-ethynyl-2'-deoxyuridine (EdU) assay in both diabetic and wild-type mice. The morphological changes of RPE cells were evaluated by using Voronoi diagram from immunostaining for ß-catenin. Characteristics of regenerated cells were evaluated by quantifying the mRNA and protein levels of RPE and epithelial-mesenchymal transition (EMT) markers. There were significantly less EdU-positive cells in laser-treated areas in diabetic mice than wild-type mice. Hexagonality was extensively lost in diabetic mice. Many EdU-positive cells were co-localized with Otx2-positive cells in the center of the laser-treated areas in wild-type mice, but only EdU-positive cells were widely distributed in diabetic mice. Quantitative analysis of mRNA and protein levels showed that the expression levels of RPE markers, Pax6, Mitf, and Otx2, were significantly decreased in RPE of diabetic mice compared with that of wild-type mice, whereas the expression levels of EMT markers, vimentin and fibronectin, were significantly increased. The proliferation and hexagonality of regenerating RPE cells were impaired after laser photocoagulation, and the regenerated RPE cells lost their original properties in diabetic mice. Further clinical research is needed to elucidate the RPE response after laser photocoagulation in diabetic patients.

The role of Wnt/ß-catenin signaling in the restoration of induced pluripotent stem cell-derived retinal pigment epithelium after laser photocoagulation.

To investigate the role of Wnt/ß-catenin signaling pathway in the restoration of induced pluripotent stem cell-derived retinal pigment epithelium (hiPSC-RPE) after laser photocoagulation. After differentiation of RPE cells from hiPSCs, laser photocoagulation was performed. Activation of Wnt/ß-catenin signaling at days 1 and 5 after laser photocoagulation was evaluated by expression of ß-catenin. Cell proliferation and alteration in cell-to-cell contact at day 5 after laser photocoagulation with or without Dickkopf-1 (Dkk-1) treatment were studied using ethynyl-2'-deoxyuridine (EdU) assay and zonula occludens-1 (ZO-1) expression analysis, respectively. The mRNA levels of Wnt genes at day 5 after laser photocoagulation were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Activation of Wnt/ß-catenin signaling at days 1 and 5 after laser photocoagulation was confirmed by ß-catenin accumulation in the cytoplasm and nucleus of hiPSC-RPE. Many EdU-positive cells also expressed ß-catenin, and the number of EdU-positive cells was decreased at day 5 after laser photocoagulation after Dkk-1 treatment, indicating that Wnt/ß-catenin signaling mediated hiPSC-RPE proliferation. ZO-1 expression was not decreased with Dkk-1 treatment at day 5 after laser photocoagulation, indicating that Wnt/ß-catenin signaling mediated hiPSC-RPE restoration. At day 5, after laser photocoagulation, mRNA levels of Wnt2b, Wnt3, Wnt5a, Wnt7a, and Wnt10b were increased. Wnt/ß-catenin signaling has a crucial role in restoration of hiPSC-RPE proliferation after laser photocoagulation. Manipulation of Wnt/ß-catenin signaling while elucidating the underlying mechanisms of RPE restoration might have a therapeutic potential in retinal degenerative diseases.

Long-term Change of Subfoveal Choroidal Thickness in Behçet's Disease Patients with Posterior Uveitis.

PURPOSE: To evaluate long-term changes of subfoveal choroidal thickness (SCT) in Behçet's disease (BD) patients with posterior uveitis. METHODS: Changes in SCT measured with enhanced depth imaging optical coherence tomography during quiescent phase were assessed during >24 months in 63 BD patients and control group. RESULTS: Baseline characteristics showed no difference, but the BD group showed poorer visual acuity (p = 0.013) and smaller SCT (p = 0.006) at final examination. Mean SCT in the BD group decreased from 291.0 to 268.1 µm (p<0.001) during the mean period of 38.5 months. Mean change rate of SCT in the BD group was greater than controls (-7.2 vs 2.0 µm/year; p<0.001) and was associated with longer active inflammation (p<0.001). Patients with longer disease duration showed smaller baseline SCT (p = 0.03). CONCLUSIONS: In BD patients, choroidal thickness decreased over time, which was associated with length of active inflammation. It suggests intraocular inflammation in BD affects the choroid as well as the retina.

En face optical coherence tomography findings in a case of Alport syndrome.

Alport syndrome is a rare hereditary disease that is associated with retinal abnormalities such as dot-and-fleck retinopathy and temporal macular thinning. The main pathophysiological process of Alport syndrome is loss of the collagen network in the basement membrane. However, the alterations in each retinal layer have not been fully evaluated. In the case presented here, we evaluated the retina of a patient with Alport syndrome using en face optical coherence tomography (OCT). The findings suggested that the primary alterations occur in the internal limiting membrane and the retinal pigment epithelium basement membrane which is a part of the Bruch's membrane. The adjacent retinal layers are damaged subsequently. In conclusion, en face OCT could be useful in evaluating retinal abnormalities and understanding their underlying pathophysiology in Alport syndrome.

The effect on choroidal changes of the route of systemic corticosteroids in acute Vogt-Koyanagi-Harada disease.

PURPOSE: To determine whether route of corticosteroid administration during the acute stage of Vogt-Koyanagi-Harada (VKH) disease affects depigmentary change and subfoveal choroidal thickness (SCT) during the convalescent stage. METHODS: In this retrospective comparative study, VKH patients with the interval between diagnosis and final follow-up of ≥ 24 months were divided into two groups according to route of systemic corticosteroid; intravenous pulse therapy (IV pulse group) and oral administration (oral group). Sunset glow fundus (SGF) scores determined by ultra-wide field retinal imaging and SCT determined by enhanced depth imaging optical coherence tomography were compared. RESULTS: Forty eyes (20 patients) were included in the IV pulse group and 33 eyes (18 patients) in the oral group. At final follow-up, the IV pulse group showed significantly lower mean SGF score, indicating less advanced depigmentary change (3.7 ± 1.5 vs. 5.1 ± 1.2, P = 0.007) and greater mean SCT (239.7 ± 71.1 µm vs. 183.8 ± 72.6 µm, P = 0.012) than the oral group. However, visual acuities did not differ (P = 0.245). In a cross-sectional evaluation at multiple time points from disease onset, the IV pulse group showed significantly lower SGF scores from 1 to 6 years and greater SCTs from 2 to 5 years. Multivariable regression analysis showed that IV pulse therapy and less frequent and shorter duration of inflammation predicted a lower SGF score (R2 = 0.291, P < 0.001), and young age, IV pulse therapy, and shorter duration of inflammation predicted greater SCT (R2 = 0.27, P < 0.001). CONCLUSIONS: Compared to oral administration, high dose IV pulse corticosteroids during the acute stage of VKH disease resulted in less choroidal change during the convalescent stage.