Comparison between optic neuritis associated with antibody against myelin oligodendrocyte glycoprotein and presumed idiopathic optic perineuritis.

BACKGROUND: The aim of this study was to determine important clinical and radiological features that aid in distinguishing presumed idiopathic optic perineuritis (OPN) from optic neuritis (ON) associated with antibody against myelin oligodendrocyte glycoprotein (MOG-Ab). METHODS: This retrospective, case-control study recruited patients with MOG-Ab-associated ON from 2011 through 2018 and idiopathic OPN from 2009 through 2011. The presence of MOG-Ab was not investigated in idiopathic OPN, because MOG-Ab testing was not available until 2011. The clinical and radiological features and the disease course were compared between the two patient groups. RESULTS: A total of 48 patients with MOG-Ab-associated ON were identified. These included 15 patients showing optic nerve sheath enhancement (ONSE) and 33 with only optic nerve enhancement. Ocular pain with ocular movement and optic disc swelling were more common in patients with ONSE, who also exhibited a poorer initial visual acuity than did those without ONSE. However, the response to steroid treatment, incidence of relapse after steroid treatment, and visual outcome at the last visit were similar between subgroups. The clinical and radiological features and treatment outcome were similar between these patients with OPN and patients with MOG-Ab-associated ON with ONSE. On the other hand, the clinical features of MOG-Ab-associated ON without ONSE differed from those of idiopathic OPN. CONCLUSION: Our findings showed a substantial proportion of ONSE in patients with MOG-Ab-associated ON. In view of the similarities between these patients and patients with OPN, MOG-Ab testing should be performed in all patients with idiopathic OPN.

Once-daily, prolonged-release tacrolimus vs twice-daily, immediate-release tacrolimus in de novo living-donor liver transplantation: A Phase 4, randomized, open-label, comparative, single-center study.

Randomized, open-label, comparative, single-center, Phase 4, 24-week study comparing pharmacokinetics (PK), safety, and efficacy of once-daily, prolonged-release tacrolimus (PR-T) with twice-daily, immediate-release tacrolimus (IR-T) in adult de novo living-donor liver transplant (LDLT) recipients in Korea. All patients received intravenous tacrolimus from Day 0 (transplantation) for 4 days and were randomized (1:1) to receive oral PR-T or IR-T from Day 5. PK profiles were taken on Days 6 and 21. Primary endpoint: area under the concentration-time curve over 24 hour (AUC0-24 ). Predefined similarity interval for confidence intervals of ratios: 80%-125%. Secondary endpoints included: tacrolimus concentration at 24 hour (C24 ), patient/graft survival, biopsy-confirmed acute rejection (BCAR), treatment-emergent adverse events (TEAEs). One-hundred patients were included (PR-T, n = 50; IR-T, n = 50). Compared with IR-T, 40% and 66% higher mean PR-T daily doses resulted in similar AUC0-24 between formulations on Day 6 (PR-T:IR-T ratio of means 96.8%), and numerically higher AUC0-24 with PR-T on Day 21 (128.8%), respectively. Linear relationship was similar between AUC0-24 and C24 , and formulations. No graft loss/deaths, incidence of BCAR and TEAEs similar between formulations. Higher PR-T vs IR-T doses were required to achieve comparable systemic exposure in Korean de novo LDLT recipients. PR-T was efficacious; no new safety signals were detected.

Comparison of the anti-inflammatory effects of induced pluripotent stem cell-derived and bone marrow-derived mesenchymal stromal cells in a murine model of corneal injury.

BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) offer tremendous potential for therapeutic applications for inflammatory diseases. However, tissue-derived MSCs, such as bone marrow-derived MSCs (BM-MSCs), have considerable donor variations and limited expandability. It was recently demonstrated that MSCs derived from induced pluripotent stem cells (iPSC-MSCs) have less pro-tumor potential and greater expandability of homogenous cell population. In this study, we investigated the anti-inflammatory effects and mechanism of iPSC-MSCs in a murine model of chemical and mechanical injury to the cornea and compared the effects with those of BM-MSCs. METHODS: To create an injury, ethanol was applied to the corneal surface in mice, and the corneal epithelium was removed with a blade. Immediately after injury, mice received an intravenous injection of (i) iPSC-MSCs, (ii) BM-MSCs or (iii) vehicle. Clinical, histological and molecular assays were performed in the cornea to evaluate inflammation. RESULTS: We found that corneal opacity was significantly reduced by iPSC-MSCs or BM-MSCs. Histological examination revealed that the swelling and inflammatory infiltration in the cornea were markedly decreased in mice treated with iPSC-MSCs or BM-MSCs. Corneal levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were lower in iPSC-MSC- and BM-MSC-treated mice, compared with vehicle-treated controls. In contrast, iPSC-MSCs with a knockdown of the TNF-α stimulating gene (TSG)-6 did not suppress the levels of inflammatory cytokines and failed to reduce corneal opacity. CONCLUSIONS: Together these data demonstrate that iPSC-MSCs exert therapeutic effects in the cornea by reducing inflammation in part through the expression of TSG-6, and the effects are similar to those seen with BM-MSCs.

Portal vein stenting as a significant risk factor for biliary stricture in adult living donor liver transplantation.

BACKGROUND: Although perioperative portal vein (PV) stent implantation is an effective treatment for steno-occlusive disease in adult living donor liver transplantation (LDLT) recipients, we experienced high incidence of biliary anastomotic strictures (BAS) after PV stenting. In this study, we sought to clarify the relation between BAS and PV stenting and to suggest the possible mechanism of BAS and measures to reduce its incidence. METHODS: We retrospectively analyzed 44 LDLT recipients who underwent PV stent implantation across the line of PV anastomosis regardless of the location of steno-occlusion (stent group) and their matched controls (non-stented LDLT recipients, n=131). RESULTS: The incidence of BAS was higher in patients in the stent group than that in the control group (43.2% vs 17.6%, P=0.001). Cumulative 6-month and 1-, 2- and 5-year BAS rates were 31.8%, 34.1%, 41.4% and 43.2%, respectively, in the stent group and 13.0%, 13.8%, 16.1% and 17.8%, respectively, in the control group (P=0.001). Multivariate analysis revealed that PV stenting was an independent risk factor for BAS. CONCLUSIONS: Although PV stent implantation is a reliable treatment modality for steno-occlusive PV in adult LDLT recipients, innovative methods to prevent the PV stent from crossing the line of PV anastomosis may be necessary to reduce the incidence of postoperative BAS.

Toxicity and efficacy of type I interferons on the ocular surface: in vitro, animal, and clinical studies.

PURPOSE: To investigate the toxicity of type I interferons (IFNs) on the ocular surface and assess their efficacy in ocular surface tumors. METHODS: We examined the effects of IFN-α2a, IFN-α2b and IFN-ß on corneal epithelial cells and stromal fibroblasts in vitro as well as the impact of IFN-α2a on the ocular surface in mice. Additionally, we analyzed the therapeutic and adverse effects of topically administered IFN-α2a and IFN-α2b in patients with ocular surface tumors. Risk factors contributing to side effects were explored. RESULTS: IFN-α2a, IFN-α2b or IFN-ß reduced cell viability and induced pro-inflammatory cytokines in corneal epithelial cells and stromal fibroblasts. Furthermore, IFNs enhanced the expression of major histocompatibility complex class II and CD40 in corneal epithelial cells. In mice, subconjunctival IFN-α2a injection did not induce corneal epithelial defects or opacity, nor did it reduce aqueous tears or conjunctival goblet cells. In patients, topical IFN-α2a or IFN-α2b administration decreased tumor size and prevented recurrence; however, it was associated with mild side effects, including corneal epitheliopathy and conjunctival hyperemia. These complications were associated with longer IFN use, the presence of underlying ocular surface disease and concurrent use of mitomycin C or anti-glaucoma eye drops. CONCLUSION: Although type I IFNs cause direct toxicity on corneal cells, they do not induce significant side effects on the healthy ocular surface. Considering its therapeutic and preventive effects, topical type I IFN is safe and effective for treating ocular surface tumors. The potential for ocular side effects should be considered in eyes with identified risk factors.

Screening fundus photography predicts and reveals risk factors for glaucoma conversion in eyes with large optic disc cupping.

This study aimed to investigate the risk factors for glaucoma conversion and progression in eyes with large optic disc cupping without retinal nerve fiber layer defect (RNFLD). Five hundred forty-two eyes of 271 subjects who had a vertical cup-to-disc ratio (CDR) ≥ 0.6 without RNFLD were enrolled. Characteristics for optic disc configuration (including CDR, vertical cupping, ISNT rule, disc ovality, peripapillary atrophy [PPA]-to-disc area [DA] ratio, and lamina cribrosa pore visibility) and blood vessels (including central retinal vessel trunk [CRVT] nasalization, bayoneting of vessels, baring of circumlinear vessels, history of disc hemorrhage [DH] and vessel narrowing/sclerotic change) were evaluated. From a median follow-up of 11.3 years, 26.6% of eyes (n = 144) developed RNFLD within a median of 5.1 years. Baseline factors, including vertical CDR ≥ 0.7 (hazard ratio [HR] = 2.12), vertical cupping (HR = 1.93), ISNT rule violation (HR = 2.84), disc ovality ≥ 1.2 (HR = 1.61), PPA-to-DA ratio ≥ 0.4 (HR = 1.77), CRVT nasalization ≥ 60% (HR = 1.77), vessel narrowing/sclerotic change (HR = 2.13), DH history (HR = 5.60), and baseline intraocular pressure ≥ 14 mmHg (HR = 1.70) were significantly associated with glaucoma conversion (all Ps < 0.05). An HR-matched scoring system based on initial fundus photography predicted glaucoma conversion with specificity of 90.4%. Careful examination of the optic nerve head and vascular structures can help to predict the risk of glaucoma conversion in eyes with large optic disc cupping.

Mesenchymal stromal cells for corneal transplantation: Literature review and suggestions for successful clinical trials.

Corneal transplantation is a routine procedure for patients with corneal blindness. Despite the streamlining of surgical techniques and deeper understanding of the cellular and molecular pathways mediating rejection, corticosteroids are still the main immunosuppressive regimen in corneal transplantation, and the 15-year survival of corneal transplants remains as low as 50%, which is poorer than that for most solid organ transplants. Recently, mesenchymal stromal cells (MSCs) with unique regenerative and immune-modulating properties have emerged as a promising cell therapy to promote transplant tolerance, minimize the use of immunosuppressants, and prevent chronic rejection. Here, we review the literature on preclinical studies of MSCs for corneal transplantation and summarize the key findings from clinical trials with MSCs in solid organ transplantation. Finally, we highlight current issues and challenges regarding MSC therapies and suggest strategies for safe and effective MSC-based therapies in clinical transplantation.

Peripapillary vessel parameters and mean ocular perfusion pressure in young healthy eyes: OCT angiography study.

BACKGROUND: To investigate the relationship between estimated mean ocular perfusion pressure (MOPP) and peripapillary perfusion density (PD) or vessel density (VD) as measured by spectral-domain optical coherence tomography angiography (OCTA) in young healthy eyes. METHODS: 132 healthy participants (264 eyes) under 45 years of age underwent optic disc OCTA scan sized 3×3 mm to acquire PD and VD in the superficial vascular complex (SVC). Optic nerve head (ONH) parameters including retinal nerve fibre layer (RNFL) thickness, rim area and disc area were measured. MOPP was estimated from systemic blood pressure and intraocular pressure (IOP). A linear mixed model was used to find the systemic and ocular factors associated with PD and VD. RESULTS: The average age of the subjects was 25.8±6.5 years. PD and VD showed a significant correlation with RNFL thickness (r=0.224, p<0.001 and r=0.214, p<0.001, respectively), but with MOPP, the correlation was only marginally significant (r=0.105, p=0.09 and r=0.112, p=0.07, respectively). After controlling for confounding factors, including age, sex, IOP, central corneal thickness, axial length and OCTA signal strength, PD and VD were significantly associated with ONH parameters (all p<0.05) but not with estimated MOPP (all p>0.05). CONCLUSION: PD and VD in the SVC were significantly associated with ONH parameters while showing no association with estimated MOPP. OCTA-derived VD may not represent perfusion pressure, but is rather more dependent on peripapillary structure.

Clinical Characteristics of Patients with Intermittent Exotropia According to the Response to Short-term Prism Adaptation Test.

PURPOSE: To evaluate the prevalence of the prism adaptation response in patients with intermittent exotropia (IXT) using the short-term prism adaptation test (PAT) and to assess factors associated with prism adaptation response in IXT patients. METHODS: A case-controlled retrospective analysis was performed on 113 patients with IXT without prior surgical treatment. Age, sex, visual acuity, refraction, stereoacuity, control scale, type of exotropia, history of occlusion, and presence of accompanying visual symptoms were recorded. Prism alternate cover test (PACT) was performed with fixation targets at 6 m and 1/3 m. All patients underwent short-term PAT wearing prism glasses that offset the exodeviation previously measured by PACT. After 30 minutes, angle deviation was measured, and patients were classified into either an increase group, which had an increase in deviation ≥5 prism diopters after short-term PAT, or a no-change group. Analysis was performed to investigate the clinical factors influencing the increase in exodeviation after short-term PAT. RESULTS: Fifty patients (44.2%) showed an increase ≥5 prism diopters during distance or near fixation after short-term PAT compared to the previous PACT: 12 patients (10.6%) showed an increment at distance fixation, and 45 patients (39.8%) showed an increase at near fixation. At distance fixation, the increase-group had a significantly smaller maximum angle measured by PACT. At near distance, age at PAT, maximum distance angle, minimum distance angle, maximum near angle, minimum near angle, angle fluctuation at near, and IXT type showed significant associations with positive short-term PAT response. In the multivariate analysis, older age and smaller maximum near angle were significantly associated with positive short-term PAT response at near fixation. CONCLUSIONS: Short-term PAT could be helpful in older IXT patients with a small maximum angle of deviation at near fixation to mitigate the vergence aftereffect and show the maximum angle of deviation.

Quantitative analysis of neural tissues around the optic disc after panretinal photocoagulation in patients with diabetic retinopathy.

In this retrospective cross-sectional study, we quantitatively analyzed the tomographic features in the neural tissues around the optic disc in patients with diabetic retinopathy with and without panretinal photocoagulation. We analyzed 206 eyes, comprising 33 normal eyes in subjects without diabetes (group I), 30 eyes without diabetic retinopathy (group II), 66 eyes with non-proliferative diabetic retinopathy (group III), 45 eyes with panretinal photocoagulation (group IV), and 32 eyes with normal tension glaucoma (group V). Sequential images acquired using swept-source optical coherence tomography in three-dimensional mode were used to measure peripapillary retinal nerve fiber layer thickness, neuro-retinal rim thickness, anterior lamina cribrosa depth, prelaminar thickness, and thickness of the lamina cribrosa. The peripapillary retinal nerve fiber layer thickness and lamina cribrosa thickness were significantly thinner in group IV than in group III (p = 0.019 and p < 0.001). However, there was no significant difference in rim thickness, anterior lamina cribrosa depth, or prelaminar thickness between groups III and IV (p = 0.307, p = 0.877, and p = 0.212). Multivariate analysis revealed that time since panretinal photocoagulation and thickness of the lamina cribrosa had a significant effect on peripapillary retinal nerve fiber layer thickness (p < 0.001 and p = 0.014). In group IV, there was a negative correlation between time elapsed since panretinal photocoagulation and peripapillary retinal nerve fiber layer thickness, rim thickness, and thickness of the lamina cribrosa (r = -0.765, r = -0.490, and r = -0.419), but no correlation with prelaminar thickness or anterior lamina cribrosa depth (r = 0.104 and r = -0.171). Panretinal photocoagulation may be related to thinning of the peripapillary retinal nerve fiber layer, rim thickness, and lamina cribrosa, but not prelaminar thickness or anterior lamina cribrosa depth. These features are different from the peripapillary features of eyes with typical normal tension glaucoma.