Non-apoptotic regulated cell death in Fuchs endothelial corneal dystrophy.

Introduction: Fuchs endothelial corneal dystrophy (FECD) is the leading cause of corneal blindness in developed countries. Corneal endothelial cells in FECD are susceptive to oxidative stress, leading to mitochondrial dysfunction and cell death. Oxidative stress causes many forms of cell death including parthanatos, which is characterized by translocation of apoptosis-inducing factor (AIF) to the nucleus with upregulation of poly (ADP-ribose) polymerase 1 (PARP-1) and poly (ADP-ribose) (PAR). Although cell death is an important aspect of FECD, previous reports have often analyzed immortalized cell lines, making the evaluation of cell death difficult. Therefore, we established a new in vitro FECD model to evaluate the pathophysiology of FECD. Methods: Corneal endothelial cells were derived from disease-specific induced pluripotent stem cells (iPSCs). Hydrogen peroxide (H2O2) was used as a source for oxidative stress to mimic the pathophysiology of FECD. We investigated the responses to oxidative stress and the involvement of parthanatos in FECD-corneal endothelial cells. Results: Cell death ratio and oxidative stress level were upregulated in FECD with H2O2 treatment compared with non-FECD control, indicating the vulnerability of oxidative stress in FECD. We also found that intracellular PAR, as well as PARP-1 and AIF in the nucleus were upregulated in FECD. Furthermore, PARP inhibition, but not pan-caspase inhibition, rescued cell death, DNA double-strand breaks, mitochondrial membrane potential depolarization and energy depletion, suggesting that cell death was mainly due to parthanatos. Conclusions: We report that parthanatos may be involved in the pathophysiology of FECD and targeting this cell death pathway may be a potential therapeutic approach for FECD.

A Comprehensive Assessment of Tear-Film-Oriented Diagnosis (TFOD) in a Dacryoadenectomy Dry Eye Model.

Tear film instability is a major cause of dry eye disease. In order to treat patients with short tear film breakup time (TBUT)-type dry eye, the development of tear film stabilizing agents is essential. However, the lack of an appropriate animal model of tear film instability has made drug development difficult. Although rabbit dry eye models have been reported in the past, there are only a few reports that focus on tear film instability. Herein, we assessed the tear film stability of a rabbit dry eye model induced by dacryoadenectomy. A clinical evaluation of the ocular surface, interferometry, and histological assessments of the cornea and conjunctiva were performed. Following the removal of the lacrimal glands, TBUT was shortened significantly, with dimple and random breakup patterns prominently observed. Furthermore, the blink rate in this model increased after dacryoadenectomy, suggesting that this model partially captured the phenotypes of human short TBUT-type dry eye and may be useful as an animal model for investigating potential drug candidates.

Annular choroidal detachment following intravitreal aflibercept injection in a patient with nivolumab treatment: a case report.

BACKGROUND: To present a novel case that developed annular choroidal detachment after intravitreal anti-vascular endothelial growth factor antibody injection in a patient after immune checkpoint inhibitor treatment. CASE PRESENTATION: A 58-year-old Japanese man presented visual impairment in the right eye. Ophthalmological examination revealed macular edema in the right eye, which suggested the possibility of age-related macular degeneration. Following the intravitreal aflibercept injection, the annular choroidal detachment was observed in the injected eye. As hypotony or thick sclera was not observed, choroidal detachment seemed to have appeared due to enhanced inflammation by intravitreal injection. The patient had a history of stage IV paranasal cavity cancer and was treated with nivolumab, an immune checkpoint inhibitor. The immune response might have been enhanced due to the use of nivolumab so that intravitreal injection triggered inflammation. Three weeks after sub-tenon injection of triamcinolone acetonide, macular edema and choroidal detachment improved. CONCLUSIONS: Intravitreal aflibercept injection caused annular choroidal detachment in our patient, presumably because the immune system was activated after nivolumab treatment. To the best of our knowledge, this is the first case report of annular choroidal detachment that developed after intravitreal injection in a patient with a history of nivolumab therapy. With the increasing use of immune checkpoint inhibitors in patients with various cancers, clinicians should be aware of these potentially associated immune-related adverse events.

Micro-incision vitrectomy surgery for primary rhegmatogenous retinal detachments with posterior vitreous detachments in elderly patients: Preoperative characteristics and surgical outcomes.

PURPOSE: To assess the preoperative characteristics and surgical outcomes of using micro-incision vitrectomy surgery (MIVS) to treat RRD with posterior vitreous detachment (PVD) in an older and a younger patient group. METHODS: This retrospective cohort study included 407 eyes from 397 patients with primary RRD with PVD who were consecutively treated in our hospital from February 2016 to February 2020. PVD was diagnosed clinically by the presence of a Weiss ring, or was diagnosed morphologically via optical coherence tomography and subsequently confirmed during surgery. The main outcome measures were preoperative RRD characteristics, best-corrected visual acuity (BCVA), and postoperative complications. RESULTS: Data were analysed from 55 eyes in the elderly group (age 70 and older), and 352 eyes in the young group (age 69 and younger). There was no significant inter-group difference in the initial reattachment rate. Preoperative characteristics indicated that elderly patients had a significantly lower rate of phakic eyes, shorter mean axial length, lower lattice incidence, and longer time spans from onset to surgery. There were no significant between-group differences in the incidence of the following complications: fibrin formation, intraocular pressure elevation, epi-retinal membrane on the macula, intraocular lens optic capture, proliferative vitreoretinopathy, and vitreous haemorrhage. While the elderly patients had significant postoperative improvements in BCVA, these improvements were significantly lower than those of the younger patients. CONCLUSIONS: This study highlighted the characteristics and surgical outcomes of MIVS in elderly patients with RRD. Although the time from onset to surgery was longer, MIVS still can be performed safely to improve older patients' postoperative BCVA.