Inhibiting corneal transplantation rejection via lymphatic vessel ligation in a novel murine model.

The lymphatic system is a crucial contributor to allograft rejection after corneal transplantation. However, no surgical procedures for the central pathway where conjunctival lymphatic vessels converge have been investigated. Therefore, we aimed to establish a murine model of lymphatic vessel ligation and evaluate its inhibitory effect on corneal allograft rejection. A tracer was used to visualise lymphatic vessels, and complications were evaluated. A surgical technique was developed to block the lymphatic vessels. Corneas from C57BL/6 mice were transplanted into BALB/c mice divided into two groups-one with and one without lymphatic vessel ligation, to evaluate their effects on allograft rejection. Graft opacity scores were evaluated for 8 weeks, and immunohistochemistry was used to quantify angiogenesis and lymphangiogenesis. 20% trypan blue used as a tracer showed clear inflow with no complications. The two sutures and cyanoacrylate glue combination demonstrated a blocking effect after 25 days and was thus used for lymphatic ligation. Three and nine out of fourteen eyes showed rejection at 8 weeks post-surgery in the lymphatic vessel ligation and control groups, respectively. Furthermore, neovascularisation and lymphangiogenesis significantly decreased in the lymphatic vessel ligation group. Overall, we present a novel therapeutic strategy for corneal transplantation.

Busin Glide-Assisted Pull-Through Insertion of Artificial Corneal Endothelium (EndoArt).

Background: Currently, the push-in technique through the corneal tunnel using a blunt-tip spatula is used to insert an artificial corneal endothelium (EndoArt) into the anterior chamber (AC). The device is useful for patients with bullous keratopathy; however, it may be difficult to manipulate the very thin implant through hazy cornea. Unlike DMEK graft, it cannot be stained and the F-mark is faint. So, visualizing and orienting the implant is a real challenge especially through a hazy cornea and inadequate AC visualization. Therefore, alternative EndoArt implantation techniques are needed in patients with advanced endothelial dysfunction to avoid complications. Purpose: To report an alternative technique for EndoArt implantation using a Busin glide. Technique: The EndoArt was loaded onto the Busin glide with the concave side of the EndoArt facing upward and was then pulled/pushed into the Busin glide opening. After the Descemet's membrane and endothelium were detached and removed in a circular fashion in a patient with advanced corneal endothelial decompensation, the Busin glide was inserted into the corneal incision, and the EndoArt was slowly pulled into the AC using retractor forceps. Finally, the air was injected into the AC. Conclusion: The Busin glide-assisted pull-through technique smoothly and securely inserted the EndoArt into the AC without upside-down attachment. This alternative technique can be useful for patients with a history of repeat intraocular surgeries or trauma with severe corneal edema to avoid potential complications such as epithelial implantation cysts or downgrowth.

Importance of Higher-Order Aberrations on Both Anterior and Posterior Surfaces After Pterygium Surgery.

PURPOSE: The purpose of this study was to investigate the changes in higher-order aberrations (HOAs), coma, and spherical aberrations (SAs) on the anterior, posterior, and total corneal surfaces after pterygium excision. METHODS: In this single-center study, we examined 19 eyes of 15 patients who underwent pterygium excision at Yokohama Minami Kyosai Hospital between January 2017 and December 2017. We also evaluated 25 eyes of 25 age-matched patients with no history of ocular disease as the control group. Corneal topography, total HOAs, coma, and SAs in all regions at 4 and 6 mm diameters were evaluated using anterior segment optical coherence tomography (CASIA SS-1000, Tomey, Japan). The pterygium area and extent were also assessed. RESULTS: Significant improvements in the HOAs, coma, and SAs at both diameters were observed in the total and anterior corneas from the first postoperative month. Notably, the posterior cornea showed significant improvements in HOAs (4 mm: P < 0.001 [log HOAs]; 6 mm: P = 0.001 [log HOAs]) and coma (4 mm: P = 0.003 [log coma], 6 mm: P = 0.002 [log coma]) within both diameters at 1 month postoperatively. A strong correlation was identified among the pterygium area, posterior HOAs, and coma (Spearman correlation = 0.651). Pterygium induced 2 D of astigmatism when extension exceeded 2.1 mm. CONCLUSIONS: HOAs in both the anterior and posterior corneas improved after pterygium excision. This finding underscores the importance of considering corneal aberrations on both anterior and posterior surfaces in pterygium management.

Descemet Membrane Endothelial Keratoplasty in Corneal Endothelial Decompensation After a Forceps-Induced Corneal Birth Injury: Case Series and Technique.

PURPOSE: The aim of this study was to describe the efficacy of Descemet membrane endothelial keratoplasty (DMEK) in patients with corneal endothelial decompensation secondary to a forceps-induced corneal birth injury. METHODS: This was a retrospective, noncomparative, interventional case series. Four eyes of 4 patients (1 female and 3 males; mean age, 64.0 ± 4.7 years) with corneal endothelial decompensation due to forceps-induced corneal birth injury were included. DMEK was performed in all cases, using a combined technique, including the use of intraoperative optical coherence tomography, vital staining of Descemet membrane of both host and donor, removal of scarred Descemet membrane with side-port forceps and vitreous cutter to smoothen the posterior corneal surface, epithelial peeling, and illumination for visualization. The examination included preoperative and postoperative ophthalmologic examinations: best-corrected visual acuity (converted to logarithm of the minimum angle of resolution [logMAR]), intraocular pressure, endothelial cell density (ECD), and central corneal thickness. RESULTS: No postoperative complications were noted, and corneal transparency was maintained during follow-up (mean follow-up period, 32.0 ± 27.0 months; range, 3-71 months). The mean best-corrected visual acuity was 0.52 ± 0.35 logMAR preoperatively and 0.15 ± 0.09 logMAR at the last visit. The mean postoperative ECD was 1632 ± 631 cells/mm2 (mean ECD at baseline, 3167 cells/mm2). Central corneal thickness decreased from 640 ± 67 µm preoperatively to 576 ± 58 µm postoperatively. CONCLUSIONS: This study suggests that DMEK can be performed uneventfully in eyes with a forceps-induced corneal birth injury. The combination of surgical techniques may be an effective approach for DMEK.

Retinal Injury Activates Complement Expression in Müller Cells Leading to Neuroinflammation and Photoreceptor Cell Death.

Retinal detachment (RD) is a neurodegenerative blinding disease caused by plethora of clinical conditions. RD is characterized by the physical separation of retina from the underlying retinal pigment epithelium (RPE), eventually leading to photoreceptor cell death, inflammation, and vision loss. Albeit the activation of complement plays a critical role in the pathogenesis of RD, the retinal cellular source for complement production remains elusive. Here, using C3 tdTomato reporter mice we show that retinal injury upregulates C3 expression, specifically in Müller cells. Activation of the complement cascade results in the generation of proinflammatory cleaved products, C3a and C5a, that bind C3aR and C5aR1, respectively. Our flow cytometry data show that retinal injury significantly upregulated C3aR and C5aR1 in microglia and resulted in the infiltration of peripheral immune cells. Loss of C3, C5, C3aR or C5aR1 reduced photoreceptor cell death and infiltration of microglia and peripheral immune cells into the sub-retinal space. These results indicate that C3/C3aR and C5/C5aR1 play a crucial role in eliciting photoreceptor degeneration and inflammatory responses in RD.

Incidence of Graft Rejection in Descemet Membrane Endothelial Keratoplasty After COVID-19 mRNA Vaccination.

PURPOSE: The aim of this study was to investigate the Descemet membrane endothelial keratoplasty (DMEK) rejection rate after COVID-19 vaccination with an mRNA vaccine. METHODS: This was a multicenter, retrospective cohort study. A total of 198 patients who underwent DMEK between January 2006 and December 2020 were divided into 2 cohorts: consecutive patients who received at least 1 COVID-19 vaccination in 2021 (vaccination started from February 2021 in Japan) and nonvaccinated patients (control cohort). Patients who had a postoperative observation period of less than 90 days were excluded. The main outcome measurement was the incidence of graft rejection. A Cox proportional hazards regression model was used for comparisons with the nonvaccinated group. RESULTS: Six rejection episodes were observed in 198 patients (124 nonvaccinated and 74 vaccinated patients), with 1 occurring in the nonvaccinated group and 5 in the vaccinated group. In the univariate model, vaccination had a significant effect on rejection episodes ( P = 0.003). The effect of vaccination was also significant ( P = 0.004) after adjusting for covariates. CONCLUSIONS: This study suggests that there may be a higher rejection rate after COVID-19 vaccination in patients who underwent DMEK. Patients should be warned of the rejection risk and its typical symptoms before receiving an mRNA COVID-19 vaccine, although further larger studies are needed to confirm the involvement of vaccination.

Microglia refine developing retinal astrocytic and vascular networks through the complement C3/C3aR axis.

Microglia, a resident immune cell of the central nervous system (CNS), play a pivotal role in facilitating neurovascular development through mechanisms that are not fully understood. Previous reports indicate a role for microglia in regulating astrocyte density. This current work resolves the mechanism through which microglia facilitate astrocyte spatial patterning and superficial vascular bed formation in the neuroretina during development. Ablation of microglia increased astrocyte density and altered spatial patterning. Mechanistically, we show that microglia regulate the formation of the spatially organized astrocyte template required for subsequent vascular growth, through the complement C3/C3aR axis during neuroretinal development. Lack of C3 or C3aR hindered the developmental phagocytic removal of astrocyte bodies and resulted in increased astrocyte density. In addition, increased astrocyte density was associated with elevated proangiogenic extracellular matrix gene expression in C3- and C3aR-deficient retinas, resulting in increased vascular density. These data demonstrate that microglia regulate developmental astrocyte and vascular network spatial patterning in the neuroretina via the complement axis.

[Initial and Long-term Results of Omental Flap Coverage for the Complications after Thoracic Aortic Aneurysm Repair].

OBJECTIVE: Here, we will review the initial remote results of omental flap coverage (OFC) after thoracic aortic aneurysm repair and report on its efficacy and problems. METHODS: We performed 567 thoracic aortic aneurysm surgeries from January 2007 to December 2021, including OFC in 16 patients( 2.8%, 10 males, mean age 65 years:range 30-82 years) who underwent OFC. RESULTS: OFC was performed in 14 cases of mediastinitis and 2 cases of perigraft seroma. 13 cases were performed at the same admission as the initial surgery, and 3 cases were performed after the discharge. The causative organisms of mediastinitis were methicillin-resistant Staphylococcus aureus (MRSA) in 4 cases, methicillin-resistant coagulase negative Staphylococcus( MRCNS) in 2 cases, Staphylococcus, Acinetobacter, Klebsiella, and methicillin-resistant Staphylococcus epidermidis( MRSE) in 1 case each, and unknown in 4 cases. All cases underwent successful reoperation with OFC alone, except in 1 case in which redo root replacement was performed for an anastomotic pseudoaneurysm. The overall hospital mortality was 31% (4 cases for MOF, 1 case for anastomotic hemorrhage). Of the 11 patients who were discharged alive, two died remotely (heart failure, senility), and no cases of reinfection were encountered. CONCLUSION: OFC is an effective treatment not only for mediastinitis but also for perigraft seroma while significantly reducing the risk of reinfection.

HLA-A26 is a risk factor for Behçet's disease ocular lesions.

BACKGROUND: How HLA-A26 modulates Behçet's disease (BD) ocular lesions such as iridocyclitis and retinochorioiditis has not been scrutinized. METHODS: Ministry of Health, Labour and Welfare of Japan provided us a database of BD patients who were registered from 2003 to 2014. We selected patients who satisfied International Criteria for BD and whose data for HLA-A26 was available. RESULTS: Eligible 557 patients consisting of 238 men (42.7%) and 319 women (57.3%), whose median age was 38 years old (interquartile range 29-47) were analyzed. Prevalence of general ocular lesions, iridocyclitis, retinochorioiditis, and chronic lesions were 43.1%, 30.7%, 34.1%, and 17.4%, respectively. The prevalence of ocular lesions was higher among HLA-A26 carriers compared to that among HLA-A26 non-carriers with odds ratio (OR) of 2.5 (95% confidence interval (95% CI) 1.8-3.5, p < .001) for general ocular lesions, OR of 2.5 (95% CI 1.7-3.6, p < .001) for iridocyclitis, OR of 2.8 (95% CI 1.9-4.0, p < .001) for retinochorioiditis, and OR of 2.7 (95% CI 1.7-4.3, p < .001) for 'chronic ocular lesion following iridocyclitis or retinochorioiditis'. The HLA-A26 had a similar impact on ocular lesions between HLA-B51 positive and negative cases (Breslow-Day test, p > .05). However, the HLA-A26 had a larger impact on iridocyclitis for men compared to women (Breslow-Day test, p = .040). The male HLA-A26 carriers had higher risk of iridocyclitis with OR of 3.4 (95% CI 2.0-5.9, p < .001), while the OR for women was 1.5 (95% CI 0.9-2.6, p = .146). CONCLUSION: HLA-A26 carriers had higher risk for iridocyclitis and retinochorioiditis. However, the impact was more prominent for men.

Pars plana vitrectomy combined with penetrating keratoplasty and transscleral-sutured intraocular lens implantation in complex eyes: a case series.

BACKGROUND: The aim of this study was to evaluate the clinical outcomes of pars plana vitrectomy (PPV) combined with penetrating keratoplasty (PKP) and transscleral-sutured intraocular lens (IOL) implantation (IOL-suture) in complex eyes. METHODS: In this prospective, consecutive interventional case series, patients who underwent PKP combined with PPV and IOL implantation from July 2014 to March 2018 at Yokohama Minami Kyosai Hospital were enrolled. The postoperative best corrected visual acuity (BCVA) (converted to logarithm of the minimal angle of resolution [logMAR] units), intraocular pressure (IOP, mmHg), endothelial cell density (ECD, cells/mm2), graft survival, complications, astigmatism, and spherical equivalent (dioptres [D]) were evaluated. RESULTS: This study included 11 eyes of 11 patients (three females and eight males; mean age, 61.8 ± 13.9 years) with an injury (n = 6) or bullous keratopathy (n = 5). The BCVA significantly improved from 1.50 ± 0.66 logMAR preoperatively to 0.78 ± 0.59 logMAR (p < 0.001) postoperatively. The baseline ECD significantly decreased from 2396 ± 238 cells/mm2 preoperatively to 1132 ± 323 cells/mm2 (p < 0.001) postoperatively. Despite two rejection episodes, graft survival rates were 100%. The mean follow-up period was 38.0 ± 20.5 months. Two patients required combined glaucoma surgery, and three patients underwent subsequent glaucoma surgery. Postoperative astigmatism and spherical equivalent were 3.9 ± 3.2 D and 0.29 ± 2.18 D, respectively. CONCLUSION: The combination of PKP, PPV, and IOL-suture implantation could be a safe and effective approach for eyes requiring anterior segment surgery; however, these eyes are associated with a higher incidence of glaucoma surgery.

The influence of HLA-B51 on clinical manifestations among Japanese patients with Behçet's disease: A nationwide survey.

Objectives: To scrutinize the influence of HLA-B51 to each clinical manifestation of patients with Behçet's disease (BD) using a database of the Ministry of Health, Labour and Welfare of Japan.Methods: The database of newly registered patients with BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met International Criteria for Behçet's Disease (ICBD) and had data for HLA-B51 were selected and analyzed.Results: Among the 3044 analyzable cases, 1334 (43.8%) were men and 1710 (56.2%) were women; the median age was 38 years (IQR 29-48). HLA-B51 was positive for 1334 (44.5%). Prevalence of selected manifestations was 98.5% for oral ulceration, 85.5% for skin lesion, 42.1% for ocular lesion, 69.1% for genital ulceration, and 29.0% for gastrointestinal symptom. HLA-B51-positive patients had higher risk for ocular lesion (OR 1.59, 95%CI: 1.37-1.84; p < .001) and lower risk for genital ulceration (OR 0.72, 95%CI: 0.62-0.84; p < .001) and gastrointestinal symptom (OR 0.65, 95%CI: 0.55-0.77; p < .001). No significant difference was observed for other organ involvement; oral ulceration, skin lesion, positive pathergy test, arthritis, epididymitis, vascular lesion, or neurological manifestation. Subgroup analyses revealed that HLA-B51 was not related to genital ulceration in the cases with an ICBD score of 6 or higher and that HLA-B51 tended to more largely affect the risk of three manifestations for men compared to that for women.Conclusion: HLA-B51 positive is a risk factor for ocular lesion and vice versa for genital ulceration and gastrointestinal symptoms in patients with Japanese BD.

Iris Posterior Synechiae After Descemet Membrane Endothelial Keratoplasty in Asian Eyes: Prevention and Management of Posterior Synechiae.

OBJECTIVES: To evaluate the efficacy of a mydriatic agent for posterior synechiae after phacoemulsification and intraocular lens (IOL) implantation followed by Descemet membrane endothelial keratoplasty (staged DMEK). METHODS: In this prospective study, the outcomes of DMEK with or without mydriasis (0.5% tropicamide and 0.5% phenylephrine hydrochloride [Mydrin-P; Santen, Osaka, Japan]) after the DMEK procedure were analyzed. Patients underwent IOL implantation approximately 4 weeks before DMEK. Six months after DMEK, the iris posterior synechiae severity score was evaluated based on the extent of posterior synechiae affecting the eight areas (45° each) of the pupillary rim (posterior synechiae score; grades 0-8). Best spectacle-corrected visual acuity, central corneal thickness, endothelial cell density, axial length, and the amount of air at the end of the surgery were also evaluated. RESULTS: Fifteen eyes of 15 patients (mydriatic: n=8, control: n=7) were eligible for inclusion. Iris posterior synechiae were detected in all seven eyes (100.0%) in the control group, whereas they were noted in two eyes in the mydriatic group (25%). The mean iris posterior synechiae score was 0.69±1.20 in the mydriatic group and was significantly lower than that in the control group (4.57±0.90; P<0.001). There was no significant difference in other clinical factors. Although the incidence and scores of posterior synechiae in the control group were higher, the incidence was significantly reduced with the use of a mydriatic agent (in the mydriatic group). CONCLUSIONS: Use of a mydriatic agent is an effective measure to prevent postoperative synechiae after DMEK.

Effect of Graft Shift Direction on Graft Detachment and Endothelial Cell Survival After Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To investigate the effects of graft shift orientation on clinical outcomes after Descemet membrane endothelial keratoplasty (DMEK). METHODS: This study used intraoperative video images to retrospectively examine the effect of graft shift direction in 50 eyes of 50 patients. Correlations were assessed between graft shift direction and multiple parameters. RESULTS: The graft detachment rate was higher in eyes with an inferior graft shift than in those without (superior, 0% and 5.0%; nasal, 0% and 20.0%; inferior, 16.7% and 55.0%; temporal, 16.7% and 45.0%; and any segment, 23.3% and 65.0%; for graft shift-negative and graft shift-positive cases, respectively). Postoperative endothelial cell density reduction was higher in eyes with an inferior graft shift (1 month, 23.6% ± 13.7% and 37.5% ± 18.8%; 3 months, 31.6% ± 16.4% and 45.2% ± 15.2%; and 6 months, 39.8% ± 14.9% and 50.7% ± 16.6%; for graft shift-negative and graft shift-positive cases, respectively). Eyes with a superior graft shift had lower postoperative endothelial cell density reduction than those without (1 month, 36.9% ± 16.6% and 20.0% ± 13.1%; 3 months, 45.3% ± 13.3% and 27.4% ± 16.2%; and 6 months, 51.3% ± 14.6% and 35.9% ± 14.5%; for graft shift-negative and graft shift-positive cases, respectively). Graft shift direction did not affect postoperative best-corrected visual acuity or central corneal thickness. CONCLUSIONS: Graft shift direction in DMEK, especially inferior graft shift, affected the postoperative graft detachment rate. Superior graft shift had a beneficial effect on postoperative corneal endothelial values. These data suggest that inferior graft shift should be avoided in DMEK.

The association analysis between HLA-A*26 and Behçet's disease.

The strongest genetic risk factor of Behçet's disease (BD) is HLA-B*51. Our group previously reported that HLA-A*26 is independently associated with the risk of the onset of BD apart from HLA-B*51. Here, we re-evaluated the association between HLA-A*26 and BD in the Japanese population. We also performed a comprehensive literature search and meta-analyzed the extracted published data concerning the relationship between HLA-A*26 and BD to estimate the odds ratio (OR) of HLA-A*26 to BD. In this study, we genotyped 611 Japanese BD patients and 2,955 unrelated ethnically matched healthy controls. Genotyping results showed that the phenotype frequency of HLA-A*26 was higher in BD patients than in controls (OR = 2.12, 95% CI: 1.75-2.56). Furthermore, within the HLA-B*51-negative populations, the phenotype frequency of HLA-A*26 was significantly higher in BD patients than in controls (OR = 3.10, 95% CI: 2.43-3.95). Results obtained from meta-analysis combined with our data showed that the modified OR of HLA-A*26 became 1.80 (95% CI:1.58-2.06), whereas within the HLA-B*51-negative population, the modified OR became 4.02 (95% CI: 2.29-7.05). A subgroup analysis arranged by the geographical regions showed HLA-A*26 is in fact associated with the onset of BD in Northeast Asia (OR = 2.11, 95% CI: 1.75-2.56), but not in the Middle East or in Europe.

Comparison of trypan blue and Brilliant Blue G for staining of the anterior lens capsule during cataract surgery: short-term results.

PURPOSE: The present study aimed to evaluate the potential corneal endothelial cell toxicity of trypan blue (TB) and Brilliant Blue G (BBG), two dyes used to stain the anterior capsule in cataract surgery. METHODS: We conducted a single-center, prospective, randomized study in which 150 eyes of 117 patients were randomly divided into control (CT), TB, and BBG groups. Preoperative and postoperative (1, 3, and 6 months) values for corrected distance visual acuity (CDVA), corneal endothelial cell count, and central corneal thickness were compared among the three groups. RESULTS: A total of 111 eyes from 88 patients were completely analyzed. The CDVA (logarithm of the minimal angle of resolution) values in the CT, TB, and BBG groups 1 month after surgery were 0.001, 0.023, and 0.019, respectively. The corneal endothelial cell counts 6 months after surgery were 2711 ± 225, 2748 ± 251, and 2680 ± 284 cells/mm2, respectively. The central corneal thicknesses 6 months after surgery were 524.3 ± 35.5, 532.2 ± 36.1, and 531.4 ± 33.0 µm, respectively. There were no significant differences in CDVA, endothelial cell count, or central corneal thickness among the three groups during the follow-up period. CONCLUSIONS: Our findings indicate that neither TB nor BBG was associated with detectable toxicity to corneal endothelial cells during cataract surgery, even when injected directly into the anterior chamber. Additionally, BBG exhibited equivalent staining efficiency to TB.

Short Axial Length and Iris Damage Are Associated With Iris Posterior Synechiae After Descemet Membrane Endothelial Keratoplasty in Asian Eyes.

PURPOSE: To evaluate the frequency and severity of iris posterior synechiae after Descemet membrane endothelial keratoplasty (DMEK) and to investigate possible causes of iris posterior synechiae. METHODS: Twenty-three eyes were investigated in 20 Asian patients who underwent DMEK 1 month after phacoemulsification and intraocular lens implantation surgery. A preexisting iris damage score was defined by iris damage and classified into 5 grades. Six months after DMEK, the iris posterior synechiae severity score was evaluated based on the extent of posterior synechiae, according to every 45 degrees of the pupillary rim (posterior synechiae score, 0-8). Correlations were analyzed between the posterior synechiae score and preexisting factors (preexisting iris damage score, axial length [AXL], anterior chamber depth, and anterior chamber volume, both before and after cataract surgery). RESULTS: Iris posterior synechiae appeared in 20 of 23 eyes (87.0%). Best spectacle-corrected visual acuity significantly improved at 6 months after DMEK (P < 0.001). Endothelial cell density was 1596 ± 530 cells/mm (P < 0.001); loss of cell density was 37.8 ± 19.9% at 6 months. Single regression analysis showed that the onset of iris posterior synechiae was correlated with the preexisting iris damage score (P = 0.006, r = 0.55), AXL (P < 0.001, r = -0.71), anterior chamber depth (P < 0.001, r = -0.70), and anterior chamber volume before cataract surgery (P < 0.001, r = -0.79). CONCLUSIONS: Iris posterior synechiae after DMEK frequently appeared in Asian eyes with shorter AXLs or a damaged iris.