Senescent characteristics of human corneal endothelial cells upon ultraviolet-A exposure.

PURPOSE: The objective of this study was to investigate the senescent phenotypes of human corneal endothelial cells (hCEnCs) upon treatment with ultraviolet (UV)-A. METHODS: We assessed cell morphology, senescence-associated ß-galactosidase (SA-ß-gal) activity, cell proliferation and expression of senescence markers (p16 and p21) in hCEnCs exposed to UV-A radiation, and senescent hCEnCs induced by ionizing radiation (IR) were used as positive controls. We performed RNA sequencing and proteomics analyses to compare gene and protein expression profiles between UV-A- and IR-induced senescent hCEnCs, and we also compared the results to non-senescent hCEnCs. RESULTS: Cells exposed to 5 J/cm2 of UV-A or to IR exhibited typical senescent phenotypes, including enlargement, increased SA-ß-gal activity, decreased cell proliferation and elevated expression of p16 and p21. RNA-Seq analysis revealed that 83.9% of the genes significantly upregulated and 82.6% of the genes significantly downregulated in UV-A-induced senescent hCEnCs overlapped with the genes regulated in IR-induced senescent hCEnCs. Proteomics also revealed that 93.8% of the proteins significantly upregulated in UV-A-induced senescent hCEnCs overlapped with those induced by IR. In proteomics analyses, senescent hCEnCs induced by UV-A exhibited elevated expression levels of several factors part of the senescence-associated secretory phenotype. CONCLUSIONS: In this study, where senescence was induced by UV-A, a more physiological stress for hCEnCs compared to IR, we determined that UV-A modulated the expression of many genes and proteins typically altered upon IR treatment, a more conventional method of senescence induction, even though UV-A also modulated specific pathways unrelated to IR.

Donor Corneal Endothelial Cell Maturity and Its Impact on Graft Survival in Glaucoma Patients Undergoing Corneal Transplantation.

PURPOSE: To examine corneal graft survival via corneal endothelial cell density (ECD) and corneal endothelial cell loss (ECL) at 5 years post-transplantation in the eyes of patients with and without a history of undergoing glaucoma surgery according to the maturity of the donor corneal endothelial cells. DESIGN: Prospective cohort study. METHODS: This prospective cohort study included 17 patients with glaucoma and 51 patients without glaucoma who underwent Descemet's stripping automated endothelial keratoplasty or penetrating keratoplasty at the Baptist Eye Institute, Kyoto, Japan, between October 2014 and October 2016. Human corneal endothelial cells were cultured from residual peripheral donor cornea tissue, and the maturity of the cells was evaluated by cell surface markers (ie, CD166+, CD44-/dull, CD24-, and CD105-) using fluorescence-activated cell sorting. Kaplan-Meier analysis or the chi-square test was used to assess the rate of successful corneal graft survival post-transplantation. RESULTS: At 36 months postoperatively, the mean ECD and ECL in the glaucoma-bleb eyes were 1197 ± 352 cells/mm2 and 55.5% ± 13.9% in the high-maturity group and 853 ± 430 cells/mm2 and 67.7% ± 18.1% in the low-maturity group, respectively. Kaplan-Meier analysis revealed that at 5 years postoperatively, the overall rate of survival was 45%, that is, 100% in the high-maturity group and 25% in the low-maturity group (P < .05). CONCLUSIONS: The findings in this prospective cohort study revealed that the use of donor corneal grafts containing mature-differentiated corneal endothelial cells could maintain the survival of the transplanted graft for a long-term period, even in patients with a history of undergoing glaucoma surgery.

The existence of senescent cells in conjunctival epithelium from elderly individuals.

PURPOSE: The ocular surface microenvironment changes with aging. However, it remains unclear if cellular senescence influences the ocular surface. We investigated the presence of p16INK4a-expressing senescent cells in healthy human conjunctiva. STUDY DESIGN: Clinical and experimental. METHODS: Healthy conjunctival tissue samples were obtained from middle-aged and elderly subjects. RT-qPCR was performed to assess the expression of senescence markers CDKN2A (p16INK4a) and CDKN1A (p21CIP1/WAF1) and immunostaining was performed to examine the expression of the senescence marker p16INK4a, stem cell markers Ki67 and p63, tight-junction marker ZO-1. RESULTS: Our study involved 19 conjunctival tissue samples (10 elderly and 9 middle-aged), mean age [elderly: 75.8 ± 3.7 years (72-81), middle-aged: 52.7 ± 7 years (38-59)], sex (elderly: 3 men, 7 women; middle-aged: 3 men, 6 women). The expression of p16INK4a was significantly increased at the RNA level in the elderly compared to middle-aged (p < 0.05). Positivity rate of p16INK4a was significantly elevated in the elderly (15.0 ± 7.8%) compared to middle-aged (0.2 ± 0.6%) (p < 0.05). Positivity rate of Ki67and p63 was significantly reduced in the elderly (1.7 ± 1.7% and 16.5 ± 9.5%) compared to middle-aged (3.9 ± 1.8% and 24.7 ± 5.7%) (p < 0.05). ZO-1 expression was reduced in tissue samples showing p16INK4a-positivity but retained in tissue samples in which p16INK4a was undetectable. CONCLUSIONS: Senescent cells accumulate with age in the conjunctival epithelium, accompanied by a decrease in Ki67, p63 and ZO-1 expressing cells.

Strategic combination of cultivated oral mucosal epithelial transplantation and postoperative limbal-rigid contact lens-wear for end-stage ocular surface disease: a retrospective cohort study.

PURPOSE: To provide the long-term outcome of patients with end-stage severe ocular surface disease (OSD) consecutively treated with cultivated oral mucosal epithelial transplantation (COMET) followed by limbal-rigid contact lens (CL)-wear therapy. DESIGN: Retrospective cohort. METHODS: In 23 eyes of 18 patients with severe OSD who underwent COMET surgery between 2002 and 2019 and who were followed with limbal-rigid CL-wear therapy for at least 1 year postoperative, patient demographics, best-corrected visual acuity (BCVA, logMAR), Ocular Surface Grading Scores (OSGS), surgical indication and adverse events were reviewed. Primary and secondary outcomes were BCVA and OSGS changes at baseline and final examination, respectively. RESULTS: This study involved 16 patients with Stevens-Johnson syndrome and 2 patients with mucous membrane pemphigoid (mean age: 59±15 years). The indications for COMET were as follows: corneal reconstruction for vision improvement (10 eyes (43.5%)), corneal reconstruction for persistent epithelial defect (4 eyes (17.4%)) and conjunctival (fornix) reconstruction for symblepharon release (9 eyes (39.1%)). The mean duration of CL-wear postsurgery was 6.4±3.9 years (range: 1.4 to 13.3 years). The mean BCVA at baseline and at final follow-up was logMAR 1.9±0.5 and 1.3±0.7, respectively (p<0.05). Compared with those at baseline, the OSGSs for symblepharon and upper and lower fornix shortening showed significant improvement at each follow-up time point post treatment initiation. No serious intraoperative or postoperative adverse events were observed. CONCLUSION: In patients afflicted with severe OSD, COMET combined with limbal-rigid CL-wear therapy postsurgery was found effective for vision improvement and ocular surface stabilisation.

Gene expression signatures of human senescent corneal and conjunctival epithelial cells.

PURPOSE: This study aimed to investigate the senescent phenotypes of human corneal and conjunctival epithelial cells. METHODS: We examined cell morphology, senescence-associated ß-galactosidase (SA-ß-gal) activity, cell proliferation, and expression of senescence markers (p16 and p21). RNA sequencing analysis was conducted to compare gene expression profiles between senescent and non-senescent cells. Finally, the potential involvement of senescent cells in the pathogenesis of ocular surface diseases was investigated. RESULTS: X-irradiated corneal and conjunctival epithelial cells exhibited typical senescence phenotypes, i.e., flattened morphologies, increased SA-ß-gal activity, decreased cell proliferation, and increased expression of senescence markers, p16 and p21. RNA-seq analysis revealed substantial differences in gene expression profiles between senescent corneal (SCo) and conjunctival epithelial cells (SCj). Moreover, SCj were detected in pathological conjunctival tissues associated with limbal stem cell deficiency (LSCD) due to Stevens-Johnson syndrome or chemical burns, potentially being involved in abnormal differentiation. CONCLUSION: This study highlights the cellular and molecular characteristics of senescent ocular surface cells, particularly in SCj that show abnormal keratin expression, and their potential roles in severe ocular surface diseases and pathology.

Role of the Senescence-Associated Factor Dipeptidyl Peptidase 4 in the Pathogenesis of SARS-CoV-2 Infection.

During cellular senescence, persistent growth arrest and changes in protein expression programs are accompanied by a senescence-associated secretory phenotype (SASP). In this study, we detected the upregulation of the SASP-related protein dipeptidyl peptidase 4 (DDP4) in human primary lung cells rendered senescent by exposure to ionizing radiation. DPP4 is an exopeptidase that plays a crucial role in the cleavage of various proteins, resulting in the loss of N-terminal dipeptides and proinflammatory effects. Interestingly, our data revealed an association between severe coronavirus disease 2019 (COVID-19) and DDP4, namely that DPP4 levels increased in the plasma of patients with COVID-19 and were correlated with age and disease progression. Although we could not determine the direct effect of DDP4 on viral replication, mechanistic studies in cell culture revealed a negative impact on the expression of the tight junction protein zonula occludens-1 (ZO-1), which contributes to epithelial barrier function. Mass spectrometry analysis indicated that DPP4 overexpressing cells exhibited a decrease in ZO-1 and increased expression of pro-inflammatory cytokines and chemokines. By investigating the effect of DPP4 on the barrier function of human primary cells, we detected an increase in ZO-1 using DPP4 inhibitors. These results provide an important contribution to our understanding of DPP4 in the context of senescence, suggesting that DPP4 plays a major role as part of the SASP. Our results provide evidence that cellular senescence, a hallmark of aging, has an important impact on respiratory infections.

Twelve-year outcome of Rho-associated protein kinase inhibitor eye drop treatment for Fuchs endothelial corneal dystrophy: A case study.

Purpose: To report the safety, efficacy, and long-term outcome in a case of Fuchs endothelial corneal dystrophy (FECD) treated by Rho-associated protein kinase (ROCK)-inhibitor eye drops in combination with removal of degenerated corneal endothelial cells (CECs) subsequent to transcorneal freezing. Observations: A 52-year-old Japanese man diagnosed with early-stage FECD developed central corneal edema with decreased visual acuity (VA) in his left eye and was treated by ROCK inhibitor eye drops (Y-27632 10mM) q.i.d. for 1 week starting immediately subsequent to the removal of the damaged CECs via 2-mm-diameter transcorneal freezing in May 18, 2010. Before treatment, the best-corrected VA (BCVA) was 20/20 OD and 20/63 OS, and the central corneal thickness in the left eye was 643 µm and specular microscopy image at the central cornea was not detected due to edema. Corneal transparency recovered, and the BCVA improved to 20/20 within two weeks. At 12 years post treatment, the cornea in left eye remained transparent without corneal edema, and the CEC density at the central cornea was 1294 cells/mm2 and the central corneal thickness was 581 µm. The annual decrease of CECs at the central cornea was 1.1%, and VA was maintained at 20/25. Multiple guttae were observed in the peripheral region, but few in the central region were removed by transcorneal freezing treatment, and relatively normal and healthy CECs were observed. Conclusions and importance: The findings in this case suggest the potential long-term safety and efficacy of the medical therapy by ROCK-inhibitor eye drop for early-stage FECD.

Dyslipidemia Exacerbates Meibomian Gland Dysfunction: A Systematic Review and Meta-Analysis.

Dry eye is a multifactorial and common age-related ocular surface disease. Dyslipidemia has been reported to be involved in meibomian gland dysfunction (MGD). However, it has not been clearly identified which lipid abnormality is responsible for MGD. In this systematic review and meta-analysis, we discuss how lipid profile changes with aging is responsible for MGD development. METHODS: An article search was performed in PubMed, EMBASE, and Web of Science. Eleven studies involving dyslipidemia in patients with MGD were identified. Five out of eleven studies were further analyzed with meta-analysis. The preferred reporting items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. Study-specific estimates (prevalence of dyslipidemia in MGD patients) were combined using one-group meta-analysis in a random-effects model. RESULTS: Meta-analysis revealed that high total cholesterol (TC) and high triglycerides (TG) were significantly associated with MGD prevalence, with odds ratios of 5.245 (95% confidence interval [CI]: 1.582-17.389; p < 0.001) and 3.264 (95% CI: 1.047-10.181; p < 0.001), respectively, but high low-density lipoprotein (LDL) and low high-density lipoprotein (HDL) were not identified. Systematic review found that the percentage of MGD patients with TC ≥ 200 mg/dL ranged from 20.0-77.6%, TG ≥ 150 mg/dL ranged from 8.3-89.7%, whereas, in the aged-match-adjusted controls, TC range of 200 mg/dL or higher and TG range of 150 mg/dL was 6.1-45.1% and 1.1-47.8%, respectively. The severity of MGD was higher with dyslipidemia. CONCLUSION: Dyslipidemia and higher TC and TG are significant risk factors for MGD.

The Biologic Character of Donor Corneal Endothelial Cells Influences Endothelial Cell Density Post Successful Corneal Transplantation.

Purpose: Corneal endothelial cell density (ECD) gradually decreases after corneal transplantation by unknown biologic, biophysical, or immunologic mechanism. Our purpose was to assess the association between donor corneal endothelial cell (CEC) maturity in culture and postoperative endothelial cell loss (ECL) after successful corneal transplantation. Design: Prospective cohort study. Participants: This cohort study was conducted at Baptist Eye Institute, Kyoto, Japan, between October 2014 and October 2016. It included 68 patients with a 36-month follow-up period who had undergone successful Descemet stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty. Methods: Human CECs (HCECs) from remaining peripheral donor corneas were cultured and evaluated for maturity by surface markers (CD166+, CD44-/dull, CD24-, and CD105-) using fluorescence-activated cell sorting. Postoperative ECD was assessed according to the mature-differentiated HCEC contents: high-maturity group: > 70%, middle-maturity group: 10% to 70%, low-maturity group: < 10%. The successful rate of ECD maintained at 1500 cells/mm2 at 36 months postoperative was analyzed using the log-rank test. Main Outcome Measures: Endothelial cell density and ECL at 36 months postoperative. Results: The 68 included patients (mean [standard deviation] age 68.1 [13.6] years, 47.1% women, 52.9% DSAEK). The high, middle, and low-maturity groups included 17, 32, and 19 eyes, respectively. At 36 months postoperative, the mean (standard deviation) ECD significantly decreased to 911 (388) cells/mm2 by 66% in the low-maturity group, compared with 1604 (436) by 40% and 1424 (613) cells/mm2 by 50% in the high and middle-maturity groups (P < 0.001 and P = 0.007, respectively) and the low-maturity group significantly failed to maintain ECD at 1500 cells/mm2 at 36 months postoperative (P < 0.001). Additional ECD analysis for patients who underwent DSAEK alone displayed a significant failure to maintain ECD at 1500 cells/mm2 at 36 months postoperative (P < 0.001). Conclusions: The high content of mature-differentiated HCECs expressed in culture by the donor peripheral cornea was coincident with low ECL, suggesting that a high-maturity CEC content predicts long-term graft survival. Understanding the molecular mechanism for maintaining HCEC maturity could elucidate the mechanism of ECL after corneal transplantation and aid in developing effective interventions. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

A case of lattice corneal dystrophy type 1 with bilateral Mooren's ulcer.

Purpose: To report a rare case of lattice corneal dystrophy type 1 (LCD1) with bilateral Mooren's ulcer. Observations: This case involved a 62-year-old male patient with LCD1 who presented with the primary complaint of experiencing pain and photophobia in both eyes for 2 months prior to his initial visit. Upon examination, a peripheral corneal ulcer was observed in both eyes covering more than 3 of the 4 quadrants, accompanied with ciliary injection and severe corneal infiltration. He was diagnosed with Mooren's ulcer, and treatment with 0.1% betamethasone and 0.5% levofloxacin eye drops and systemic cyclosporine and betamethasone was initiated. At 1-month post treatment initiation, a remaining ulceration ridge was observed on the corneal surface in his left eye, which was subsequently resected. Complete epithelialization was achieved at 1-month postoperative in the left eye and after 6-months of conservative topical treatment in the right eye. At 8-9 years post onset of Mooren's ulcer, the patient underwent penetrating keratoplasty in both eyes while undergoing treatment with oral cyclosporine administration for severe corneal opacity due to progression of lattice dystrophy. Post treatment, there has been no recurrence of ulcerations, even though more that 10 years has passed since the onset of Mooren's ulcer. Conclusions and importance: To the best of our knowledge, this is the first reported case of LCD1 with bilateral Mooren's ulcer, and in this rare case, the patient was successfully treated with a combination of steroid, cyclosporine, and peripheral superficial keratectomy, and a good visual outcome was achieved after penetrating keratoplasty (PK) under the use of systemic cyclosporine.

Does senescence play a role in age-related macular degeneration?

Advanced age is the most established risk factor for developing age-related macular degeneration (AMD), one of the leading causes of visual impairment in the elderly, in Western and developed countries. Similarly, after middle age, there is an exponential increase in pathologic molecular and cellular events that can induce senescence, traditionally defined as an irreversible loss of the cells' ability to divide and most recently reported to also occur in select post-mitotic and terminally differentiated cells, such as neurons. Together these facts raise the question as to whether or not cellular senescence, may play a role in the development of AMD. A number of studies have reported the effect of ocular-relevant inducers of senescence using primarily in vitro models of poorly polarized, actively dividing retinal pigment epithelial (RPE) cell lines. However, in interpretating the data, the fidelity of these culture models to the RPE in vivo, must be considered. Fewer studies have explored the presence and/or impact of senescent cells in in vivo models that present with phenotypic features of AMD, leaving this an open field for further investigation. The goal of this review is to discuss current thoughts on the potential role of senescence in AMD development and progression, with consideration of the model systems used and their relevance to human disease.

Current Advancements in Corneal Cell-Based Therapy.

Corneal epithelial stem cells (CEpSCs) mostly reside at the limbal area and are responsible for tissue homeostasis throughout life. Once complete CEpSC deficiency occurs, regenerative medicine cell-based therapy using CEpSCs or their alternatives can provide successful clinical outcomes. Due to an improved understanding of CEpSCs and mucosal epithelial stem cells, major advancements have been made over the past few decades in in vivo and ex vivo cell-based ocular surface reconstruction therapies for the treatment of severe ocular surface diseases. New therapeutic concepts and clinical strategies are emerging for the treatment of corneal endothelial dysfunction. For example, unlike corneal epithelial cells, in vivo corneal endothelial cells (CECs) stop proliferating and are arrested in the G1 phase of the cell cycle due to cell-to-cell contact inhibition and exposure to a high concentration of transforming growth factor-beta in the aqueous humor. Thus, the production of CECs with good functionality in culture has consistently been difficult. To solve this problem, Rho-associated protein kinase inhibition has taken center stage, as it not only makes the production of human CECs in culture closely mimic the functional characteristics of in vivo healthy CECs possible but also helps sustain those biological properties. Thus, cultured human CEC injection therapy is now moving to the forefront for the treatment of corneal endothelial failure. Herein, we summarize key historical discoveries in corneal cell-based regenerative medicine and illustrate the concept of corneal cell therapy for the treatment of refractory corneal epithelial and endothelial diseases.

Prevalence of Comorbidity between Dry Eye and Allergic Conjunctivitis: A Systematic Review and Meta-Analysis.

This systematic review aimed to determine the comorbid dry eye (DE) and allergic conjunctivitis (AC) prevalence. We searched PubMed and EMBASE for articles published until 22 March 2022, combining the terms "(dry eye OR keratoconjunctivitis sicca) AND allergic conjunctivitis." Study-specific estimates (DE and AC incidence rates among patients with AC and DE, respectively) were combined using the one-group meta-analysis in a random-effects model. The initial search yielded 700 studies. Five articles reporting AC incidence among individuals with DE and six articles reporting DE incidence among individuals with AC were included in the qualitative synthesis. In these nine articles, the total sample size was 7254 patients. The DE incidence among individuals with AC was 0.9-97.5%; the AC incidence among individuals with DE was 6.2-38.0%. One-group meta-analysis using a random-effects model showed that 47.2% (95% confidence interval: 0.165-0.779; 320/1932 cases) of patients with AC had comorbid DE and 17.8% (95% confidence interval: 0.120-0.236; 793/4855 cases) of patients with DE had comorbid AC, as defined by each article. Complimentary screening and treatment for patients with DE and AC may improve long-term outcomes and prevent chronic ocular damage in highly susceptible populations.

Impact of aging on the pathophysiology of dry eye disease: A systematic review and meta-analysis.

PURPOSE: Dry eye disease (DED) is a common age-related ocular surface disease. However, it is unknown how aging influences the ocular surface microenvironment. This systematic review aims to investigate how the aging process changes the ocular surface microenvironment and impacts the development of DED. METHODS: An article search was performed in PubMed, EMBASE, and Web of Science. 44 studies reporting on age-related ocular changes and 14 large epidemiological studies involving the prevalence of DED were identified. 8 out of 14 epidemiological studies were further analyzed with meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were followed. Study-specific estimates (impact of aging on the prevalence of DED) were combined using one-group meta-analysis in a random-effects model. RESULTS: Meta-analysis revealed the prevalence of DED in the elderly aged 60 years old or older was 5519 of 60107 (9.2%) and the odds ratio of aging compared to younger age was 1.313 (95% confidence interval [CI]; 1.107, 1.557). With increasing age, the integrity of the ocular surface and tear film stability decreased. Various inflammatory cells, including senescent-associated T-cells, infiltrated the ocular surface epithelium, lacrimal gland, and meibomian gland, accompanied by senescence-related changes, including accumulation of 8-OHdG and lipofuscin-like inclusions, increased expression of p53 and apoptosis-related genes, and decreased Ki67 positive cells. CONCLUSIONS: The aging process greatly impacts the ocular surface microenvironment, consequently leading to DED.

Alteration in meibum lipid composition and subjective symptoms due to aging and meibomian gland dysfunction.

PURPOSE: To investigate the alteration in lipid composition of meibum, objective clinical signs, and subjective symptoms associated with aging and meibomian gland (MG) dysfunction (MGD). METHODS: In 10 MGD patients [4 males/6 females, mean age: 65.6 ± 7.9 years (range: 50-79 years)] and 24 healthy volunteer subjects [young subjects: 6 males/6 females, mean age: 25.7 ± 3.8 years (range: 20-35 years), elderly subjects: 6 males/6 females, mean age: 58.4 ± 7.5 years (range: 50-79 years)], three objective clinical signs were evaluated: MG orifice obstruction, meibum score, and tear film lipid layer interference pattern. Subjective symptoms were analyzed via a 15-item questionnaire. After careful collection of meibum samples, comprehensive lipid analysis was performed via liquid chromatography-mass spectrometry. Data was analyzed via JMP® ver. 13 (SAS Institute, Inc., Cary, NC) statistical analysis software. RESULTS: In the MGD patients and elderly subjects, there was a significant decrease in non-polar lipids such as cholesterol esters (ChEs), while a significant increase in polar lipids [cholesterol (Ch), (O-acyl)-ω-hydroxy fatty acid (OAHFA), and free fatty acid (FA)] in total lipids (Tukey-Kramer test: p < 0.05). Triglyceride was significantly increased only in MGD patients (p < 0.05). Symptom scores representative of vision quality (i.e., blurred vision/haziness) were significantly negatively-correlated with the ratio of the non-polar lipid ChE, while significantly positively correlated with the polar lipids Ch, OAHFA, and FA (Spearman's rank correlation coefficient: p < 0.05). CONCLUSIONS: Our findings revealed that both MGD and aging affect the composition ratio of major meibum lipids, resulting in the appearance of subjective symptoms.

The relationship between nasal and conjunctival cultures of antimicrobial-resistant isolates of methicillin-resistant Staphylococcus aureus.

PURPOSE: Nasal screening is performed to avoid the complications of postoperative surgical site infections (SSI), especially those due to antimicrobial-resistant species such as methicillin-resistant Staphylococcus aureus (MRSA). This study examined the relationship between bacterial isolates from the conjunctiva and the nasal cavity. METHODS: All patients were diagnosed with ocular surface infections, and the organisms in the conjunctiva and the nasal cavity were isolated. We investigated the relationship of the following antimicrobial-resistant bacteria between the conjunctiva and the nose: MRSA, methicillin-resistant CNS (MRCNS), levofloxacin-resistant (LVFX-R) Corynebacterium spp. Data were analyzed using Fisher's exact test, and the odds ratio was examined. RESULTS: This study included 188 eyes of 188 subjects (87 males and 101 females; mean age 58.5 years, range 11-97 years). MRSA (4 eyes), MRCNS (29 eyes), and LVFX-R Corynebacterium spp. (41 eyes) were identified from the conjunctiva, and MRSA (6 eyes), MRCNS (38 eyes), and LVFX-R Corynebacterium spp. (41 eyes) were identified from the nasal cavity. There was a significant relationship detected between the conjunctiva and the nose for MRSA, MRCNS, and LVFX-R Corynebacterium spp. MRSA displayed high sensitivity (0.750, 95% confidence interval [CI]; 0.301 to 0.987) and specificity (0.984, 95% CI; 0.953 to 0.996) in nasal cavity cultures, and the odds ratio was 181.00 times (95% CI; 18.41 to 2320). CONCLUSION: This study showed a significant relationship between conjunctival and nasal cultures of MRSA, MRCNS, and LVFX-R Corynebacterium spp., suggesting that nasal cavity culture is a potentially useful screening method for detecting resistant bacteria, especially MRSA, in the conjunctiva.

Role of Immune Cell Diversity and Heterogeneity in Corneal Graft Survival: A Systematic Review and Meta-Analysis.

Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction pathways are critical therapeutic targets. In this analysis, we aimed to review the current literature on various immunotherapeutic approaches for corneal-allograft rejection using the PubMed, EMBASE, Web of Science, Cochrane, and China National Knowledge Infrastructure. Retrievable data for meta-analysis were screened and assessed. The review, which evaluated multiple immunotherapeutic approaches to prevent corneal allograft rejection, showed extensive involvement of innate and adaptive immunity components. Understanding the contribution of this immune diversity to the ocular surface is critical for ensuring corneal allograft survival.

Structural changes of corneal epithelium in belantamab-associated superficial keratopathy using anterior segment optical coherence tomography.

PURPOSE: To describe structural changes in corneal epithelium using anterior segment optical coherence tomography (AS-OCT) in two relapsed and refractory multiple myeloma (RRMM) patients with bilateral belantamab-associated superficial keratopathy (BASK). OBSERVATIONS CASE 1: A 56-year-old male who was diagnosed with RRMM and initiated on belantamab mafodotin, presented on day 42 (three weeks after the second infusion) with decreased pinhole visual acuity from 20/20 and 20/25 to 20/70 and 20/50 in the right eye and left eye, respectively. Slit-lamp examination revealed moderate superficial keratopathy with microcystic-like epithelial changes (MECs) in the paracentral cornea in both eyes. AS-OCT demonstrated increased bilateral heterogeneous signal intensity and hyperreflective lesions as well as increased thickness in the paracentral corneal epithelium with uninvolved central cornea. Given bilateral MECs, the third infusion was withheld, and then given on day 62 after five weeks of drug-free interval. Although MECs had improved on day 82, pinhole visual acuity remained at 20/50 and 20/40 in the right eye and the left eye. AS-OCT showed that hyperreflective lesions mostly resolved and corneal epithelial thickness returned to baseline, despite a slightly increased persisting heterogeneous signal intensity in the peripheral corneal epithelium in both eyes. CASE 2: A 77-year-old male with RRMM was started on belantamab mafodotin infusions. His pinhole visual acuity decreased from 20/40 and 20/30 at baseline to 20/60 and 20/40 on day 41 (three weeks after the second infusion) in the right eye and left eye, respectively. Slit-lamp examination showed diffuse, moderate MECs in both eyes, which was more severe in the peripheral cornea. AS-OCT demonstrated increased bilateral heterogeneous signal intensity and hyperreflective lesions in the corneal epithelium, which are more severe in the right eye along with increased corneal epithelial thickness. Therefore, belantamab mafodotin was withheld. CONCLUSIONS AND IMPOTANCE: AS-OCT objectively demonstrated structural changes such as signal intensity and thickness alterations with hyperreflective lesions in the corneal epithelium related to BASK. AS-OCT might be useful for clinicians to monitor ocular surface adverse events in RRMM patients receiving belantamab mafodotin and to adjust therapeutic plans for the patients.

The Transmission of SARS-CoV-2 Infection on the Ocular Surface and Prevention Strategies.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health problem. Although the respiratory system is the main impaired organ, conjunctivitis is one of its common findings. However, it is not yet understood if SARS-CoV-2 can infect the eye and if the ocular surface can be a potential route of SARS-CoV-2 transmissions. Our review focuses on the viral entry mechanisms to give a better understanding of the interaction between SARS-CoV-2 and the eye. We highlighted findings that give evidence for multiple potential receptors of SARS-CoV-2 on the ocular surface. Additionally, we focused on data concerning the detection of viral RNA and its spike protein in the various ocular tissues from patients. However, the expression level seemed to be relatively low compared to the respiratory tissues as a result of a unique environment surrounding the ocular surface and the innate immune response of SARS-CoV-2. Nevertheless, our review suggests the ocular surface as a potential route for SARS-CoV-2 transmission, and as a result of this study we strongly recommend the protection of the eyes for ophthalmologists and patients at risk.

Current Evidence for Corynebacterium on the Ocular Surface.

Corynebacterium species are commonly found in the conjunctiva of healthy adults and are recognized as non-pathogenic bacteria. In recent years, however, Corynebacterium species have been reported to be potentially pathogenic in various tissues. We investigated Corynebacterium species on the ocular surface and reviewed various species of Corynebacterium in terms of their antimicrobial susceptibility and the underlying molecular resistance mechanisms. We identified a risk for Corynebacterium-related ocular infections in patients with poor immunity, such as patients with diabetes or long-term users of topical steroids, and in those with corneal epithelial damage due to trauma, contact lens wear, lagophthalmos, and trichiasis. The predominant strain in the conjunctiva was C. macginleyi, and the species associated with keratitis and conjunctivitis were C. macginleyi, C. propinquum, C. mastitidis, C. pseudodiphtheriticum, C. accolens, C. striatum, C. xerosis, and C. bovis. Overall, Corynebacterium species present on the ocular surface were resistant to quinolones, whereas those in the nasal cavity were more susceptible. The prevalence of fluoroquinolone-resistant Corynebacterium has not changed in the past 10 years; however, Corynebacterium species remain susceptible to third-generation cephems. In conclusion, the use of third-generation cephems should be a reasonable and pragmatic approach for treatment of ocular infections caused by Corynebacterium species.