高山 卓也

Retinal breaks are critical lesions that can cause retinal detachment and vision loss if not detected and treated early. Automated, accurate delineation of retinal breaks in ultra-widefield fundus (UWF) images remains challenging. In this study, we developed and validated a deep learning segmentation model based on the PraNet architecture to localize retinal breaks in break-positive cases. We trained and evaluated the model using a dataset comprising 34,867 UWF images of 8083 cases. Performance was assessed using image-level segmentation metrics, including accuracy, precision, recall, Intersection over Union (IoU), dice score, and centroid distance score. The model achieved an accuracy of 0.996, precision of 0.635, recall of 0.756, IoU of 0.539, dice score of 0.652, and centroid distance score of 0.081. To our knowledge, this is the first study to present pixel-level segmentation of retinal breaks in UWF images using deep learning. The proposed PraNet-based model showed high accuracy and robust segmentation performance, highlighting its potential for clinical application.

Aflibercept and brolucizumab, two anti-VEGF agents used as intravitreal injections in ophthalmology, differ significantly in molecular weight (aflibercept-115 kDa and brolucizumab-26 kDa). Using aqueous humor samples collected after drug administration, we measured and performed a comparative analysis of pharmacokinetics and half-lives of these drugs in the human eye. Since the quantification of monoclonal antibodies (mAbs) using antigen-antibody reactions, such as ELISA, is influenced by endogenous ligands or anti-drug antibodies, we employed nano-surface and molecular-orientation limited proteolysis (nSMOL), combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS), for accurate measurements. Aqueous humor samples were collected from 59 eyes of 59 patients treated with aflibercept and 52 eyes of 52 patients treated with brolucizumab. Samples were obtained with a median post-injection period of 30 (range, 2-49) days for aflibercept and 28 (range, 4-60) days for brolucizumab. A population pharmacokinetic (PPK) analysis revealed that the half-life of aflibercept in human aqueous humor was significantly shorter than that of brolucizumab, 2.88 days versus 9.00 days, respectively (p = 1.16 × 10-7). Using the same mass spectrometry conditions, we calculated the half-lives of the two drugs. These results may be useful for optimizing the efficacy of these drugs in clinical practice.

PURPOSE: We report a rare case of microbial keratitis caused by Nigrospora oryzae. OBSERVATIONS: A 72-year-old Japanese woman was injured by plant debris and developed oval corneal ulcers and hypopyon in the anterior chamber. After 5 days, she complained of pain, redness, and vision loss in her left eye and was treated with antibacterial eye drops and an ointment (1.5 % levofloxacin hydrate, cefmenoxime hydrochloride, and sterilization and disinfection eye drops; SAN-IODE and ofloxacin ophthalmic ointment). Examination revealed a worsening oval corneal ulcer with Descemet's folds and a faint hypopyon. Considering the infection from soil or plants and the poor response to intensive antibacterial eye drops, topical antifungal eye drops, i.e., 1 % voriconazole eye drops, and 1 % natamycin ointment were applied. Direct microscopy of the corneal scraping with Gram staining was performed and the result was negative. Cultures from corneal scrapings showed the growth of dark colonies after several days. The colony was identified as Nigrospora oryzae by sequencing of the fungal internal transcribed spacer region. Pain and vision loss improved with improvement in corneal ulcers. The antifungal treatment was administered for 37 days. Discontinuation of the eye drops after 1 month did not result in keratitis recurrence. At the final follow-up at 70 days, the best-corrected visual acuity was 20/25, with persistent small corneal opacity. CONCLUSIONS AND IMPORTANCE: Here, we report a case of fungal keratitis caused by Nigrospora oryzae. Microbiological identification of the causes of rare infections is difficult in clinical laboratories, necessitating the use of advanced molecular techniques based on amplification and sequencing of appropriate phylogenetic markers. Nigrospora oryzae responds to topical voriconazole and natamycin.

The estimation of central choroidal thickness from colour fundus images can improve disease detection. We developed a deep learning method to estimate central choroidal thickness from colour fundus images at a single institution, using independent datasets from other institutions for validation. A total of 2,548 images from patients who underwent same-day optical coherence tomography examination and colour fundus imaging at the outpatient clinic of Jichi Medical University Hospital were retrospectively analysed. For validation, 393 images from three institutions were used. Patients with signs of subretinal haemorrhage, central serous detachment, retinal pigment epithelial detachment, and/or macular oedema were excluded. All other fundus photographs with a visible pigment epithelium were included. The main outcome measure was the standard deviation of 10-fold cross-validation. Validation was performed using the original algorithm and the algorithm after learning based on images from all institutions. The standard deviation of 10-fold cross-validation was 73 μm. The standard deviation for other institutions was reduced by re-learning. We describe the first application and validation of a deep learning approach for the estimation of central choroidal thickness from fundus images. This algorithm is expected to help graders judge choroidal thickening and thinning.

BACKGROUND: This study reports the first cases of scleritis following intravitreal brolucizumab (IVBr) injection for nAMD, emphasizing the need to be aware of the possibility of scleritis following IVBr injections. CASE PRESENTATION: Case 1. A 74-year-old Japanese man with nAMD complained of conjunctivitis and decreased vision in the right eye 8 days after his eighth IVBr injection. Examination revealed scleritis without anterior inflammation. Topical 0.1% betamethasone and 0.3% gatifloxacin eye drops were started. The scleritis worsened in the following 2 weeks and became painful. He underwent sub-Tenon's capsule triamcinolone acetonide (STTA) injection. Two days later, he returned with a complaint of severe vision loss. Fundus examination revealed retinal artery occlusion, vasculitis, and vitreous opacity in the right eye. Vitreous surgery was performed. CASE 2: An 85-year-old Japanese woman with nAMD in the right eye complained of reddening of the eye 27 days after her fifth IVBr injection. Examination showed conjunctivitis and scleritis without anterior inflammation in the right eye. She was started on 0.1% fluorometholone and 0.5% levofloxacin hydrate eye drops. The scleritis worsened in the following 3 weeks. Her treatment was switched to 0.1% betamethasone eye drops. One month later, the scleritis had improved and a sixth IVBr injection was administered. There was no worsening of the scleritis at that time. However, 1 month after a seventh IVBr injection, she complained of severe hyperemia and decreased vision. Fundus examination revealed vitreous opacification. She underwent STTA, and the vitreous opacity improved in 24 days. Case 3. A 57-year-old Japanese man with nAMD complained of pain and decreased vision in the right eye 21 days after a fourth IVBr injection. Examination revealed scleritis with high intraocular pressure but no anterior chamber or fundus inflammation. STTA and topical eye drops were performed. One month later, scleritis improved but visual acuity didn't due to progression of nAMD. CONCLUSIONS: Intraocular inflammation following IVBr injection may progress to the posterior segment. Scleritis can occur after IVBr injection, and topical eye drops alone may not be sufficient for initial treatment. Clinicians should consider the possibility of scleritis in patients with worsening inflammation after IVBr injection.

INTRODUCTION: The aim of this study was to investigate the safety and efficacy of a single injection of intravitreal faricimab (IVF) in patients with neovascular age-related macular degeneration (nAMD) who had a prior treatment history. METHODS: A retrospective analysis was conducted on a consecutive cohort of 80 eyes of 75 patients with nAMD who had a prior history of treatment with an injection of anti-vascular endothelial growth factor. Best-corrected visual acuity (BCVA), central subfield thickness (CST), and central choroidal thickness (CCT) were compared before the initial IVF injection and after a treatment interval matching the previous duration. RESULTS: Central choroidal thickness decreased significantly following the IVF injection, but there was no significant change in BCVA or CST. Mean (± standard deviation) BCVA changed from 0.34 ± 0.37 to 0.36 ± 0.40 (P = 0.29), CST changed from 242 ± 72 to 242 ± 82 µm (P = 0.99), and CCT changed from 189 ± 98 to 179 ± 97 µm (P < 0.0001). When the changes were evaluated according to the previous anti-VEGF agent administered, CCT was found to be significantly decreased by 8.7 ± 2.5 µm (P < 0.0001) in eyes previously treated with brolucizumab and by 13.1 ± 3.6 µm (P < 0.0001) in eyes previously treated with aflibercept. No adverse events were observed during the study period. CONCLUSION: Intravitreal faricimab injection is a safe and effective treatment for nAMD in terms of short-term outcomes. Further long-term study is necessary.

The purpose of this study was to evaluate changes in the proportion of lymphoid neoplasm subtypes in South Korea. A total of 8615 cases of lymphoid neoplasms diagnosed in 1997-2016 at Samsung Medical Center in South Korea were classified according to the 2008 World Health Organization system. The total number and proportion of lymphoid neoplasms were compared between these two decades, with data from nationwide studies, and with other countries. To evaluate changes in the proportion of subtypes, crude rate of each subtype per 100 lymphoma patients during each decade and age adjusted rate were calculated. There were 3024 patients with lymphoid neoplasm in 1997-2006, and 5591 in 2007-2016, which represents an average increase of 1.85 times over the 20-year study period. Crude rate and age adjusted rate were increased in Hodgkin's lymphoma and mature B cell lymphoma while precursor lymphoid neoplasms and mature T cell lymphoma were decreased. Among B cell neoplasms, age adjusted rate of plasma cell neoplasm, follicular lymphoma, mantle cell lymphoma increased while there was no significant change in extranodal marginal zone lymphoma and Burkitt lymphoma. The increase in follicular lymphoma was due to the increases in nodal follicular lymphoma of low grade and duodenal-type follicular lymphoma. These results are consistent with the dynamics of causative factors, including socioeconomic factors, in Korea.