Artificial Intelligence for Lamellar Keratoplasty. / Künstliche Intelligenz bei lamellierenden Keratoplastiken.

The training of artificial intelligence (AI) is becoming increasingly popular. More and more studies on lamellar keratoplasty are also being published. In particular, the possibility of non-invasive and high-resolution imaging technology of optical coherence tomography predestines lamellar keratoplasty for the application of AI. Although it is technically easy to perform, there are only a few studies on the use of AI to optimise lamellar keratoplasty. The existing studies focus primarily on the prediction probability of rebubbling in DMEK and DSAEK and on their graft adherence, as well as on the formation of a big bubble in DALK. In addition, the automated recording of routine parameters such as corneal oedema, endothelial cell density or the size of the graft detachment is now possible using AI. The optimisation of lamellar keratoplasty using AI holds great potential. Nevertheless, there are limitations to the published algorithms, in that they can only be transferred between centres, surgeons and different device manufacturers to a limited extent.

Risk factors for intraocular pressure elevation following Descemet membrane endothelial keratoplasty in Asian patients.

PURPOSE: To investigate risk factors for increased intraocular pressure (IOP) after Descemet membrane endothelial keratoplasty (DMEK) in Asian patients. METHODS: Data from January 2015 to February 2021 were obtained from our prospective database. IOP elevation after DMEK was defined as IOP ≥ 22 mmHg or an increase in IOP of ≥ 10 mmHg from baseline. In addition, we examined maximum IOP. Using iCare, we measured IOP 1, 2, 3, and 6 months after DMEK, and every 6 months thereafter. Logistic regression and linear regression were performed to find factors predictive of IOP elevation and maximum IOP, respectively, based on the results of univariate analysis. RESULTS: We enrolled 90 eyes (mean patient age, 74.9 ± 7.5 years; mean follow-up duration, 25.6 ± 9.9 months) that underwent DMEK. IOP elevation was present in 19 eyes (21%). IOP increased from 12.6 ± 3.9 mmHg preoperatively to a postoperative maximum of 17.0 ± 5.5 mmHg up to 36 months after DMEK (p < 0.0001). In univariate logistic regression analysis for IOP elevation, only one variable, pseudoexfoliation syndrome (PEX) and preexisting glaucoma, was significant (p < 0.05). Preexisting glaucoma without PEX (OR, 19.33; 95% CI, 4.75-93.46), PEX without glaucoma (OR, 7.25; 95% CI, 1.20-41.63), and PEX glaucoma (OR, 58.00; 95% CI, 6.78-1298.29) were associated with higher risk of IOP elevation. CONCLUSIONS: In this cohort, the eyes of patients with PEX and preexisting glaucoma were found to be prone to IOP elevation after DMEK.

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.

A Deep Learning Approach in Rebubbling After Descemet's Membrane Endothelial Keratoplasty.

PURPOSE: To evaluate the efficacy of deep learning in judging the need for rebubbling after Descemet's endothelial membrane keratoplasty (DMEK). METHODS: This retrospective study included eyes that underwent rebubbling after DMEK (rebubbling group: RB group) and the same number of eyes that did not require rebubbling (non-RB group), based on medical records. To classify the RB group, randomly selected images from anterior segment optical coherence tomography at postoperative day 5 were evaluated by corneal specialists. The criterion for rebubbling was the condition where graft detachment reached the central 4.0-mm pupil area. We trained nine types of deep neural network structures (VGG16, VGG19, ResNet50, InceptionV3, InceptionResNetV2, Xception, DenseNet121, DenseNet169, and DenseNet201) and built nine models. Using each model, we tested the validation data and evaluated the model. RESULTS: This study included 496 images (31 eyes from 24 patients) in the RB group and 496 images (31 eyes from 29 patients) in the non-RB group. Because 16 picture images were obtained from the same point of each eye, a total of 992 images were obtained. The VGG19 model was found to have the highest area under the receiver operating characteristic curve (AUC) of all models. The AUC, sensitivity, and specificity of the VGG19 model were 0.964, 0.967, and 0.915, respectively, whereas those of the best ensemble model were 0.956, 0.913, and 0.921, respectively. CONCLUSIONS: This automated system that enables the physician to be aware of the requirement of RB might be clinically useful.

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.

Descemet's membrane endothelial keratoplasty for pseudoexfoliation syndrome: a case series.

BACKGROUND: To evaluate the clinical outcomes and features of Descemet's membrane endothelial keratoplasty (DMEK) for eyes with pseudoexfoliation syndrome (PEX). METHODS: In this retrospective study, 37 DMEK cases were reviewed from available medical records. Patients who exhibited endothelial dysfunction derived from PEX or Fuchs endothelial corneal dystrophy (FECD) and successfully underwent cataract surgery about four weeks before DMEK were enrolled. The best spectacle-corrected visual acuity (BSCVA), central corneal thickness (CCT), endothelial cell density (ECD), and incidence of intra-operative/post-operative complications of DMEK were analyzed. RESULTS: This study included 14 eyes of 14 patients (PEX: n = 6, FECD: n = 8). There was no primary graft failure. In the PEX group, BSCVA improved from 0.67 ± 0.28 at the preoperative point to 0.43 ± 0.14 at 1 month, 0.27 ± 0.10 at 3 months, and 0.19 ± 0.08 at 6 months after DMEK. The donor corneal ECD was 2704 ± 225 cells/mm2 at the preoperative point and decreased to 1691 ± 498 cells/mm2 at 1 month, 1425 ± 366 cells/mm2 at 3 months, and 1281 ± 340 cells/mm2 (52.7 ± 11.7% less than ECD of the donor graft) at 6 months after DMEK. None of the patients required rebubbling. When compared with the FECD group, no statistical difference was observed in CCT (p = 0.821); BSCVA (p = 0.001) and the reduction rate of ECD (p = 0.010) were relatively worse. CONCLUSIONS: DMEK is effective for the treatment of endothelial dysfunction due to PEX.

The ocular involvement did not accompany with the genital ulcer or the gastrointestinal symptoms at the early stage of Behçet's disease.

OBJECTIVES: This study aimed to identify patients with high-probability of ocular involvement of Behçet's disease (BD). METHODS: The Japanese Ministry of Health, Labour and Welfare provided dataset of ongoing nationwide BD registration project. A patient who had confirmed BD and who was suspected to have BD was registered. We mainly analyzed newly registered patients who had the data for all demographic and diagnostic parameters regardless of fulfilment of any diagnostic criteria. RESULTS: Among 3213 patients with confirmed or possible BD, 1382 (43.0%) were men and 1831 (57.0%) were women with a median age of 38 years (interquartile range (IQR) 30-49 years). The median duration between onset and registration was 0 year (IQR 0-3). A binomial multivariable logistic regression analysis revealed that being female (odds ratio (OR) 0.63, 95% confidence interval (CI) 0.53-0.75, p < .001), duration since onset (OR 1.33 per 10 years, 95% CI 1.18-1.51, p < .001), genital ulceration (OR 0.28, 95% CI 0.23-0.34, p < .001), and gastrointestinal symptoms (OR 0.36, 95% CI 0.30-0.44, p < .001) were related to the ocular lesion. Analyses based on data of 2800 patients who satisfied International criteria of BD, age-, sex-, duration-based subgroup analyses, analyses targeting iridocyclitis and retino-uveitis, and analysis including patients with missing data confirmed that the four factors were associated with the probability of eye involvement. CONCLUSION: The ocular involvement did not accompany with genital ulcer or gastrointestinal symptoms at the early stage of BD.

Clinical features of early-stage possible Behçet's disease patients with a variant-type major organ involvement in Japan.

Background: Clinical data of patients with entro-, vasculo-, and neuro-variant possible Behçet's disease (BD) based on Japanese criteria has not yet comprehensively reported. Methods: This ongoing nation-wide registration has been carried out by the Japanese Ministry of Health, Labour and Welfare. The Ministry asked physicians who diagnosed a patient with confirmed or possible BD to register the patient data by filling out a registration form. The Ministry provided us with the dataset after unlinkable anonymization. We analyzed 2003-2014 database generated from the early stage new cases. Results: Among the 7950 analyzable cases, 694 (8.7%) had variant-type possible BD without satisfying complete/incomplete criteria. Of the 694 patients, 479, 46, and 169 had entero-, vasculo-, and neuro-variant possible BD, respectively. Out of these 694 patients, 35 (5.0%) and 154 (22.2%) satisfied the International Study Group criteria and the International Criteria of BD, respectively. Entero-variant possible patients rarely (1.8%) had ocular lesions. Patients with vasculo-variant possible BD were featured by low genital ulceration risk (6.8%) and frequent positive HLA-B51 (60.0%). Neuro-variant possible BD was featured by high median age at registration (48 year). Vasculo- (69.6%) and neuro-variant (68.6%) BD patients showed clear male dominance. Epididymitis was very rare among variant-type possible BD men. Conclusion: We analyzed 694 early-stage variant-type possible BD cases. We believe the data from our study will contribute to further international discussion regarding BD diagnostic criteria and clarification of the clinical presentations of the Japanese variant-type possible BD patients.

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.

Discovery of a novel 2-(1H-pyrazolo[3,4-b]pyridin-1-yl)thiazole derivative as an EP1 receptor antagonist and in vivo studies in a bone fracture model.

We describe a medicinal chemistry approach to the discovery of a novel EP1 antagonist exhibiting high potency and good pharmacokinetics. Our starting point is 1, an EP1 receptor antagonist that exhibits pharmacological efficacy in cystometry models following intravenous administration. Despite its good potency in vitro, the high lipophilicity of 1 is a concern in long-term in vivo studies. Further medicinal chemistry efforts identified 4 as an improved lead compound with good in vitro ADME profile applicable to long term in vivo studies. A rat fracture study was conducted with 4 for 4 weeks to validate its utility in bone fracture healing. The results suggest that this EP1 receptor antagonist stimulates callus formation and thus 4 has potential for enhancing fracture healing.

Clinical manifestations of Behçet's disease depending on sex and age: results from Japanese nationwide registration.

Objective: This report aimed to scrutinize the prevalence of Behçet's disease (BD)-related clinical manifestations based on age- and sex-specific subgroups using a Japanese nationwide registration database. Methods: The database of newly registered BD was obtained from the Japanese Ministry of Health, Labour and Welfare. Patients who met the International Criteria for Behçet's Disease were selected and analysed. Results: Among 6627 International Criteria for Behçet's Disease cases, 2651 (40.0%) were men and 3976 (60.0%) were women with a median age of 39 years (interquartile range: 31-50 years). Ocular lesion was more common in male [odds ratio (male: female) 2.64 (95% CI: 2.35, 2.95, P < 0.001)] and genital ulceration was more common in female (odds ratio = 0.29, 95% CI: 0.25, 0.32, P < 0.001). Ocular lesion (P < 0.001), arthritis (P < 0.001) and vascular lesions (P < 0.001) were more frequently observed in elderly registered patients. Contrarily, genital ulceration (P < 0.001), epididymitis of males (P = 0.023) and oral ulceration (P = 0.003) were more common in younger patients. Simultaneous assessment of sex and age revealed that male predominance of ocular involvement was found in the young adult generation, but not in patients over 70 year of age. A female predominance of genital ulcer was prominently observed in patients 20-59 year of age; however, the sex difference was not found in patients over 60 years of age. Sensitivity analysis using International Study Group criteria replicated the results. Conclusion: We showed that clinical phenotype in early phase of BD was different depending on onset age and sex.

Suppression of Allograft Rejection with Soluble VEGF Receptor 2 Chimeric Protein in a Mouse Model of Corneal Transplantation.

When a transparent cornea becomes opaque due to infectious diseases, trauma, or ophthalmic surgery, the impaired cornea is replaced with a donor cornea to improve visual function. In this corneal transplantation, the graft survival rate is comparatively high, partly because of lacking vascular and lymphatic vessel in cornea. However, the transplanted corneas sometimes become opaque if allograft rejection occurs. Suppression of allograft rejection is critical for favorable outcomes of corneal transplantation. The essential effects of endogenous monomeric soluble vascular endothelial growth factor receptors (VEGFRs) 1 and 2 have been reported in corneal angiogenesis and lymphangiogenesis. This study investigated the effects of dimeric soluble VEGFR2/Fc chimera protein on corneal allograft rejection for future clinical application. Allogeneic full-thickness corneal transplantation was performed in C57BL/6 to BALB/c mice. The recipients were treated by intrastromal injection of soluble VEGFR1/Fc chimera (sR1/Fc group), soluble VEGFR2/Fc chimera (sR2/Fc group), or human IgG1/Fc protein (IgG/Fc group) at 0, 7, and 14 days after surgery. Both hemangiogenesis and lymphangiogenesis were significantly suppressed in the corneas of the sR2/Fc group compared with the IgG/Fc group. All grafts failed due to corneal wound rupture in the sR1/Fc group. In the sR2/Fc group, respective donor-derived MHC class II(+)/CD11c(+) cells and CD11b-positive macrophage infiltration were reduced in the DLNs and the corneas showing a negative delayed-type hypersensitivity, compared with the IgG/Fc group. Our findings demonstrate that soluble VEGFR2/Fc chimera protein efficiently suppresses corneal allo-rejection, while reducing hemangiogenesis and lymhangiogenesis, and immune-competent cell-trafficking and may be a powerful tool for corneal allograft survival.

Discovery of 2-(1H-indazol-1-yl)-thiazole derivatives as selective EP(1) receptor antagonists for treatment of overactive bladder by core structure replacement.

We have designed a series of potent EP1 receptor antagonists. These antagonists are a series of 2-(1H-indazol-1-yl)-thiazoles in which the core structure was replaced with pyrazole-phenyl groups. In preliminary conscious rat cystometry experiments, two representative candidates, 2 and 22, increased bladder capacity. In particular, the increase using 22 was approximately 2-fold that of the baseline. More detailed profiling of this compound and further optimization of this series promises to provide a novel class of drug for treating overactive bladder (OAB).

Descemet Membrane Detachment Triggered by Contrast-Enhanced Computed Tomography in a Patient with a History of Penetrating Keratoplasty for Keratoconus Treatment.

Introduction: We report a case of late-onset Descemet membrane detachment triggered by contrast-enhanced computed tomography more than 30 years after penetrating keratoplasty for keratoconus and describe its successful treatment with air tamponade. Case Presentation: A 53-year-old woman with a history of uneventful penetrating keratoplasty more than 30 years ago for keratoconus presented with acute vision loss caused by corneal edema 2 days after undergoing contrast-enhanced computed tomography. Anterior-segment optical coherence tomography (AS-OCT) revealed corneal stromal edema in the graft and Descemet's fold and partial Descemet membrane detachment without a tear. The patient received 0.1% betamethasone eye drops once every hour, along with sub-Tenon's triamcinolone acetonide injection. Anti-inflammatory treatment improved corneal edema; however, the detachment area widened. Air tamponade facilitated complete Descemet membrane reattachment and improved corneal thickness with complete restoration of visual acuity. Conclusion: An immune response may have been involved in the progression of Descemet membrane detachment in this patient. Anti-inflammatory treatment may have facilitated Descemet membrane reattachment prior to air or gas tamponade. AS-OCT is an excellent imaging modality to detect Descemet membrane detachment in eyes with presumed late penetrating graft rejection or failure.

Double-Bubble Technique Assisted by Holding Forceps: A Modified Technique in Descemet Membrane Endothelial Keratoplasty for Vitrectomized Eyes With Scleral Fixated Intraocular Lens.

PURPOSE: Several techniques have been developed for graft unfolding approaches in Descemet membrane endothelial keratoplasty (DMEK). However, despite these techniques, graft deployment and configuration in eyes with deep anterior chambers remain challenging in some cases. Therefore, in this study, we described a modified technique for DMEK, known as the "double-bubble technique assisted by holding forceps." METHODS: This was a retrospective interventional case series. Patients who underwent DMEK between August 2022 and July 2023, including cases with a history of vitrectomy and scleral fixation of intraocular lens, were enrolled in this study. Two experienced surgeons performed DMEK. In brief, after graft insertion into the anterior chamber, the first bubble with a small volume of air was injected above the graft to open the tight roll, and the graft edge was held using a 25-gauge graft manipulator. The second bubble was injected underneath the graft for fixation, while the graft edge was grasped using forceps during gas injection. The graft was released from the forceps. Best spectacle corrected visual acuity, central corneal thickness, endothelial cell density, and incidence of postoperative complications were measured before and after DMEK. RESULTS: Eleven eyes of 11 patients were included in this study (mean follow-up period, 4.5 ± 4.4 months). Best spectacle corrected visual acuity and central corneal thickness significantly improved postoperatively ( P < 0.001). Rebubbling was required in 2 eyes; no other postoperative complications or primary graft failure were observed. CONCLUSIONS: The present technique enables safe and feasible DMEK surgery in vitrectomized eyes with scleral fixated IOLs and in those with a deep anterior chamber.