Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor survival rate, largely due to the lack of early diagnosis. Although myeloid cells are crucial in the tumour microenvironment, whether their specific subset can be a biomarker of PDAC progression is unclear. METHODS: We analysed IL-22 receptor expression in PDAC and peripheral blood. Additionally, we analysed gene expression profiles of IL-10R2+/IL-22R1+ myeloid cells and the presence of these cells using single-cell RNA sequencing and murine orthotropic PDAC models, respectively, followed by examining the immunosuppressive function of IL-10R2+/IL-22R1+ myeloid cells. Finally, the correlation between IL-10R2 expression and PDAC progression was evaluated. RESULTS: IL-10R2+/IL-22R1+ myeloid cells were present in PDAC and peripheral blood. Blood IL-10R2+ myeloid cells displayed a gene expression signature associated with tumour-educated circulating monocytes. IL-10R2+/IL-22R1+ myeloid cells from human myeloid cell culture inhibited T cell proliferation. By mouse models for PDAC, we found a positive correlation between pancreatic tumour growth and increased blood IL-10R2+/IL-22R1+ myeloid cells. IL-10R2+/IL-22R1+ myeloid cells from an early phase of the PDAC model suppressed T cell proliferation and cytotoxicity. IL-10R2+ myeloid cells indicated tumour recurrence 130 days sooner than CA19-9 in post-pancreatectomy patients. CONCLUSIONS: IL-10R2+/IL-22R1+ myeloid cells in the peripheral blood might be an early marker of PDAC prognosis.

Improved predictability of pancreatic ductal adenocarcinoma diagnosis using a blood immune cell biomarker panel developed from bulk mRNA sequencing and single-cell RNA-sequencing.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a devastating cancer due to its poor survival rate, early detection, and resectability. This study aimed to determine the peripheral blood mononuclear cell (PBMC) immune biomarkers in patients with PDAC and investigate the PDAC-specific peripheral blood biomarker panel and validate its clinical performance. METHODS: In this prospective, blinded, case-control study, a biomarker panel formula was generated using a development cohort-including healthy controls, patients at high risk of PDAC, and patients with benign pancreatic disease, PDAC, or other gastrointestinal malignancies-and its diagnostic performance was verified using a validation cohort, including patients with ≥ 1 lesion suspected as PDAC on computed tomography (CT). RESULTS: RNA-sequencing of PBMCs from patients with PDAC identified three novel immune cell markers, IL-7R, PLD4, and ID3, as specific markers for PDAC. Regarding the diagnostic performance of the regression formula for the three biomarker panels, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.0%, 78.8%, 47.2%, 95.6%, and 79.8%, respectively. Based on the formula scores for the biomarker panel, the false-negative rate (FNR) of the biomarkers was 8% (95% confidence interval [CI] 3.0-13.0), which was significantly lower than that based on CT in the validation cohort (29.2%, 95% CI 20.8-37.6). CONCLUSIONS: The regression formula constructed using three PBMC biomarkers is an inexpensive, rapid, and convenient method that shows clinically useful performance for the diagnosis of PDAC. It aids diagnoses and differential diagnoses of PDAC from pancreatic disease by lowering the FNR compared to CT. Clinical trial registration Clinical Research Information Service, KCT0004614 (08 January 2020).

Efficacy and safety of 1% and 2% rebamipide clear solution in dry eye disease: a multicenter randomized trial.

BACKGROUND: To evaluate the efficacy of 1% and 2% rebamipide clear solution in the treatment of dry eye disease (DED). METHODS: Two hundred twenty patients with DED were randomly assigned to one of three groups: the 1% rebamipide, 2% rebamipide, or placebo (eye drops containing the same ingredients, except for the active components). Each eye drop was instilled four times daily for 12 weeks. Changes in tear film break-up time (TBUT), corneal and conjunctival staining score, Schirmer 1 test, and the Ocular Surface Disease Index (OSDI) from baseline to 12-week visit between the study groups were compared for efficacy assessment. RESULTS: The mean age of study patients was 43.8±14.2 years. The 1% and 2% rebamipide groups showed greater improvement in TBUT (1.99±1.87 and 2.02±2.21 s) at 12 weeks from baseline than the placebo group (1.25±2.93 s). The 2% rebamipide group showed greater improvement in the corneal staining score (- 3.15±2.00) at 12 weeks from baseline than the placebo group (- 2.85±1.80). The 1% and 2% rebamipide groups showed improvement in Schirmer 1 test (1.27±3.86 and 1.50±4.14 mm) at 12 weeks of treatment, but not the placebo group (0.55±2.99 mm). Both the rebamipide groups and the placebo group showed significantly improved OSDI after treatment for 12 weeks; however, there was no significant difference among the three groups. CONCLUSIONS: 1% and 2% rebamipide clear solutions are an effective therapeutic option for improving TBUT and tear volume, and stabilizing the corneal staining score in DED.

Integrated Analysis of Transcriptome and Proteome of the Human Cornea and Aqueous Humor Reveal Novel Biomarkers for Corneal Endothelial Cell Dysfunction.

Earlier studies have reported that elevated protein levels in the aqueous humor (AH) are associated with corneal endothelial cell dysfunction (CECD), but the details of the underlying mechanism as well as specific biomarkers for CECD remain elusive. In the present study, we aimed to identify protein markers in AH directly associated with changes to corneal endothelial cells (CECs), as AH can be easily obtained for analysis. We carried out an in-depth proteomic analysis of patient-derived AH as well as transcriptomic analysis of CECs from the same patients with bullous keratopathy (BK) resulting from CECD. We first determined differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) from CECs and AH in CECD, respectively. By combining transcriptomic and proteomic analyses, 13 shared upregulated markers and 22 shared downregulated markers were observed between DEGs and DEPs. Among these 35 candidates from biomarker profiling, three upregulated markers were finally verified via data-independent acquisition (DIA) proteomic analysis using additional individual AH samples, namely metallopeptidase inhibitor 1 (TIMP1), Fc fragment of IgG binding protein (FCGBP), and angiopoietin-related protein 7 (ANGPTL7). Furthermore, we confirmed these AH biomarkers for CECD using individual immunoassay validation. Conclusively, our findings may provide valuable insights into the disease process and identify biofluid markers for the assessment of CEC function during BK development.

Perivascular Stem Cell-Derived Cyclophilin A Improves Uterine Environment with Asherman's Syndrome via HIF1α-Dependent Angiogenesis.

Asherman's syndrome (AS) is characterized by intrauterine adhesions or fibrosis resulting from scarring inside the endometrium. AS is associated with infertility, recurrent miscarriage, and placental abnormalities. Although mesenchymal stem cells show therapeutic promise for the treatment of AS, the molecular mechanisms underlying its pathophysiology remain unclear. We ascertained that mice with AS, like human patients with AS, suffer from extensive fibrosis, oligo/amenorrhea, and infertility. Human perivascular stem cells (hPVSCs) from umbilical cords repaired uterine damage in mice with AS, regardless of their delivery routes. In mice with AS, embryo implantation is aberrantly deferred, which leads to intrauterine growth restriction followed by no delivery at term. hPVSC administration significantly improved implantation defects and subsequent poor pregnancy outcomes via hypoxia inducible factor 1α (HIF1α)-dependent angiogenesis in a dose-dependent manner. Pharmacologic inhibition of HIF1α activity hindered hPVSC actions on pregnancy outcomes, whereas stabilization of HIF1α activity facilitated such actions. Furthermore, therapeutic effects of hPVSCs were not observed in uterine-specific HIF1α-knockout mice with AS. Secretome analyses of hPVSCs identified cyclophilin-A as the major paracrine factor for hPVSC therapy via HIF1α-dependent angiogenesis. Collectively, we demonstrate that hPVSCs-derived cyclophilin-A facilitates HIF1α-dependent angiogenesis to ameliorate compromised uterine environments in mice with AS, representing the major pathophysiologic features of humans with AS.

Corneal Lymphangiogenesis: Current Pathophysiological Understandings and Its Functional Role in Ocular Surface Disease.

The cornea is a transparent and avascular tissue that plays a central role in light refraction and provides a physical barrier to the external environment. Corneal avascularity is a unique histological feature that distinguishes it from the other parts of the body. Functionally, corneal immune privilege critically relies on corneal avascularity. Corneal lymphangiogenesis is now recognized as a general pathological feature in many pathologies, including dry eye disease (DED), corneal allograft rejection, ocular allergy, bacterial and viral keratitis, and transient corneal edema. Currently, sizable data from clinical and basic research have accumulated on the pathogenesis and functional role of ocular lymphangiogenesis. However, because of the invisibility of lymphatic vessels, ocular lymphangiogenesis has not been studied as much as hemangiogenesis. We reviewed the basic mechanisms of lymphangiogenesis and summarized recent advances in the pathogenesis of ocular lymphangiogenesis, focusing on corneal allograft rejection and DED. In addition, we discuss future directions for lymphangiogenesis research.

Retraction Note: Comparison of 0.05% cyclosporine and 3% diquafosol solution for dry eye patients: a randomized, blinded, multicenter clinical trial.

An amendment to this paper has been published and can be accessed via the original article.

Protocol for the first clinical trial to investigate safety and efficacy of corneal xenotransplantation in patients with corneal opacity, corneal perforation, or impending corneal perforation.

BACKGROUND: Xenotransplantation using fresh porcine corneas has been suggested as a feasible alternative to overcome the shortage of human donor corneas. Successful long-term survival of grafts without evidence of xenozoonosis in clinically applicable pig-to-non-human primate corneal transplantation model has brought researchers close to human clinical trials. Accordingly, we aimed to prepare a clinical trial protocol to conduct the first corneal xenotransplantation. METHODS: We developed the clinical trial protocol based on international consensus statement on conditions for undertaking clinical trials of corneal xenotransplantation developed by the International Xenotransplantation Society. Detailed contents of the protocol have been modified with reference to comments provided by ophthalmologists and multidisciplinary experts, including an infectionist, an organ transplantation specialist, a clinical pharmacologist, a neuropsychiatrist, a laboratory medicine doctor, and a microbiologist. RESULTS: Two patients with bilateral legal corneal blindness (best-corrected visual acuity ≤20/200 in the better eye and ≤20/1000 in the candidate eye) or with (impending) corneal perforation will be enrolled. During the screening period, participants and their family members will have two separate deep consideration periods before signing informed consent forms. Each patient will undergo corneal xenotransplantation using fresh corneas from Seoul National University miniature pigs. Commercially available immunosuppressants will be administered and systemic infection prophylaxis will be performed according to the program schedule. After transplantation, each patient will be monitored at a specialized clinic to investigate safety up to 2 years and efficacy up to 1 year. CONCLUSIONS: A detailed clinical trial protocol for the first corneal xenotransplantation reflecting the global guidelines is provided.

Comparison of 0.05% cyclosporine and 3% diquafosol solution for dry eye patients: a randomized, blinded, multicenter clinical trial.

BACKGROUND: This study is aim to compare the clinical effectiveness between the two most prominent dry eye disease (DED)-specific eye drops, 0.05% cyclosporine (CN) and 3% diquafosol (DQ). METHODS: This is a multi-centered, randomized, masked, prospective clinical study. A total of 153 DED patients were randomly allocated to use CN twice per day or DQ six times daily. Cornea and conjunctival staining scores (NEI scale), tear break-up time (TBUT), Schirmer test scores, and ocular surface disease index (OSDI) score were measured at baseline, 4 and 12 weeks after treatment. RESULTS: At 12 weeks after treatment, NEI scaled scores were significantly reduced from the baseline by - 6.60 for CN and - 6.63 for DQ group (all P < 0.0001, P = 0.9739 between groups). TBUT and Schirmer values for CN were significantly improved from the baseline at 4 and 12 weeks (P = 0.0034, P < 0.0001 for TBUT, P = 0.0418, P = 0.0031 for Schirmer test). However, for DQ, TBUT showed significant improvement at 12 weeks only (P = 0.0281). Mean OSDI score differences from the baseline to 12 weeks were improved by - 13.03 ± 19.63 for CN and - 16.11 ± 20.87 for DQ, respectively (all P < 0.0001, P = 0.854 between groups). Regarding drug compliance, the mean instillation frequency of CN was less than that of DQ (P < 0.001). There were no statistically significant intergroup differences in safety evaluation. CONCLUSIONS: The level of improvement regarding NEI, TBUT, and OSDI scores were not significantly different between the two treatment groups. However, with regards to the early improvement of TBUT and patient compliance, patients using CN improved faster and with greater adherence to drug usage than did those treated with DQ. TRIAL REGISTRATION: KCT0002180 , retrospectively registered on 23 December 2016.

Comparison between Wavefront-optimized and corneal Wavefront-guided Transepithelial photorefractive keratectomy in moderate to high astigmatism.

BACKGROUND: To compare the clinical outcomes of wavefront-optimized (WFO) transepithelial photorefractive keratectomy (trans-PRK) and corneal wavefront-guided (CWFG) trans-PRK for myopic eyes with moderate to high astigmatism. METHODS: One hundred ninety-six eyes (196 patients) with moderate to high astigmatism (≥ 1.75 D) treated with WFO or CWFG trans-PRK (101 and 95 eyes, respectively) were retrospectively registered. Safety, efficacy, predictability, vector analysis, and corneal aberrations were compared between groups preoperatively and at 6 months postoperatively. RESULTS: At postoperative 6 months, the mean logMAR uncorrected distance visual acuity was similar in the WFO (- 0.07 ± 0.08) and CWFG (- 0.07 ± 0.07) groups. Safety, efficacy, and predictability of refractive and visual outcomes were also similar. The correction indices were 1.02 ± 0.14 and 1.03 ± 0.13 in the WFO and CWFG groups, respectively, with no significant difference. The absolute values of the angle of error were significantly higher in the WFO group (2.28 ± 2.44 vs. 1.40 ± 1.40; P = 0.002). Corneal total root mean square higher-order aberrations and corneal spherical aberrations increased postoperatively in both groups; however, the change was smaller in the CWFG group. Corneal coma showed a significant increase postoperatively only in the WFO group. CONCLUSIONS: WFO and CWFG trans-PRK are safe and effective for correcting moderate to high astigmatism. However, CWFG trans-PRK provides a more predictable astigmatism correction axis and fewer induced corneal aberrations.

Augmentation of GNSS by Low-Cost MEMS IMU, OBD-II, and Digital Altimeter for Improved Positioning in Urban Area.

This paper proposes an efficient multi-sensor system to complement GNSS (Global Navigation Satellite System) for improved positioning in urban area. The proposed system augments GNSS by low-cost MEMS IMU (Micro Electro Mechanical Systems Inertial Measurement Unit), OBD (On-Board Diagnostics)-II, and digital altimeter modules. For improved availability of time synchronization in urban area, an adaptive synchronization method is proposed to combine the external PPS (Pulse Per Second) signal and the internal onboard clock. For improved positioning accuracy and availability, a 17-state Kalman filter is formulated for efficient multi-sensor fusion, including OBD-II and digital altimeter modules. A strategy to apply different types of measurement updates is also proposed for improved performance in urban area. Four experiment results with field-collected measurements evaluates the performance of the proposed GNSS/IMU/OBD-II/altimeter system in various aspects, including accuracy, precision, continuity, and availability.

PTK7+ Mononuclear Cells Express VEGFR2 and Contribute to Vascular Stabilization by Upregulating Angiopoietin-1.

OBJECTIVE: In angiogenesis, circulating mononuclear cells are recruited to vascular lesions; however, the underlying mechanisms are poorly understood. APPROACH AND RESULTS: Here, we characterize the functional role of protein tyrosine kinase 7 (PTK7)-expressing CD11b(+) mononuclear cells in vitro and in vivo using a mouse model of angiogenesis. Although the frequencies of PTK7(+)CD11b(+) cells in the bone marrow remained similar after vascular endothelial growth factor-A-induced neovascularization, we observed an 11-fold increase in the cornea. Importantly, vascular endothelial growth factor-A-induced chemotaxis of PTK7(+) cells was mediated by vascular endothelial growth factor receptor 2. In a coculture with endothelial cells, PTK7(+)CD11b(+) cells stabilized the vascular network for 2 weeks by expressing high levels of angiopoietin-1. The enhanced vascular stability was abolished by knockdown of angiopoietin-1 in PTK7(+)CD11b(+) cells and could be restored by angiopoietin-1 treatment. CONCLUSIONS: We conclude that PTK7 expression in perivascular mononuclear cells induces vascular endothelial growth factor receptor 2 and angiopoietin-1 expression and thus contributes to vascular stabilization in angiogenesis.

Comparison of surface roughness and bacterial adhesion between cosmetic contact lenses and conventional contact lenses.

OBJECTIVE: To compare physical characteristics of cosmetic contact lenses (Cos-CLs) and conventional contact lenses (Con-CLs) that might affect susceptibility to bacterial adhesion on the contact lens (CL) surface. METHODS: Surface characteristics of Cos-CLs and Con-CLs made from the same material by the same manufacturer were measured by atomic force microscopy (AFM) and scanning electron microscopy. To determine the extent and rate of bacterial adhesion, Cos-CL and Con-CL were immersed in serum-free Roswell Park Memorial Institute media containing Staphylococcus aureus or Pseudomonas aeruginosa. Additionally, the rate of removal of adherent bacteria was evaluated using hand rubbing or immersion in multipurpose disinfecting solutions (MPDS). RESULTS: The mean surface roughness (root mean square and peak-to-valley value) measured by AFM was significantly higher for Cos-CL than for Con-CL. At each time point, significantly more S. aureus and P. aeruginosa adhered to Cos-CL than to Con-CL, which correlated with the surface roughness of CL. In Cos-CL, bacteria were mainly found on the tinted surface rather than on the noncolored or convex areas. Pseudomonas aeruginosa attached earlier than S. aureus to all types of CL. However, P. aeruginosa was more easily removed from the surface of CL than S. aureus by hand rubbing or MPDS soaking. CONCLUSIONS: Increased surface roughness is an important physical factor for bacterial adhesion in Cos-CL, which may explain why rates of bacterial keratitis rates are higher in Cos-CL users in CL physical characteristics.

Spatial epidemiology of dry eye disease: findings from South Korea.

BACKGROUND: DED rate maps from diverse regions may allow us to understand world-wide spreading pattern of the disease. Only few studies compared the prevalence of DED between geographical regions in non-spatial context. Therefore, we examined the spatial epidemiological pattern of DED prevalence in South Korea using a nationally representative sample. METHODS: We analyzed 16,431 Korean adults aged 30 years or older of the 5th Korea National Health and Nutrition Examination Survey. DED was defined as previously diagnosed by an ophthalmologist as well as symptoms experienced. Multiple logistic regression analysis was used to assess the spatial pattern in the prevalence of DED, and effects of environmental factors. RESULTS: Among seven metropolitan cities and nine provinces, three metropolitan cities located in the southeast of Korea revealed the highest prevalence of DED. After adjusting for sex, age and survey year, people living in urban areas had higher risk of having DED. Adjusted odds ratio for having previously diagnosed DED was 1.677 (95% CI 1.299-2.166) for metropolitan cities and 1.580 (95% CI 1.215-2.055) for other cities compared to rural areas. Corresponding odds ratio for presenting DED symptoms was 1.388 (95% CI 1.090-1.766) for metropolitan cities and 1.271 (95% CI 0.999-1.617) for other cities. Lower humidity and longer sunshine duration were significantly associated with DED. Among air pollutants, SO2 was associated with DED, while NO2, O3, CO, and PM10 were not. CONCLUSION: Our findings suggest that prevalence of DED can be affected by the degree of urbanization and environmental factors such as humidity and sunshine duration.

Effects of particulate matter exposure on the expression of the SARS-CoV-2 ACE2 receptor in ocular surface tissues and cells.

Particulate matter (PM) has been reported to be one of the risk factor for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, although the ocular surface is deeply affected by both PM exposure and SARS-COV-2 infection, no studies have investigated the effects of PM exposure on the ocular route of SARS-COV-2 infection. To this end, we explored the effects of PM on the expression of SARS-COV-2-associated receptors and proteins in ocular surface. Herein, short- and long-term PM-exposed rat models were established by topically administering PM for 3 and 10 days, respectively. Immortalized human corneal epithelial cells (HCECs) and human conjunctival epithelial cells (HCjECs) were exposed to PM. ACE2, TMPRSS2, CD147, and ADAM17 expression levels were measured by western blot analysis. Our results show that short-term PM exposure had little effect on the expressions of ACE2, TMPRSS2, and CD147 in ocular surface tissues. However, long-term PM exposure decreased the ACE2 expression in conjunctival tissues and increased the CD147 expression in corneal or conjunctival tissues. PM exposure reduced the ACE2 expression by increasing the ADAM17 expression and ACE2 shedding level in HCECs and HCjECs. Our findings suggest that long-term PM exposure down-regulate the expression of the SARS-CoV-2 receptor ACE2 in conjunctival tissues through ADAM17-dependent ACE2 shedding. However, long-term PM exposure up-regulates the expression of another SARS-CoV-2 receptor CD147 in ocular surface tissues, accompanied by ocular surface damage and cytotoxicity. This study provides a new insight into uncovering potential risk factors for infection with SARS-CoV-2 via the ocular route.

Flt-1 regulates vascular endothelial cell migration via a protein tyrosine kinase-7-dependent pathway.

Protein tyrosine kinase 7 (PTK7) is a pseudokinase whose precise function in regulating angiogenesis remains unknown. The purpose of this study was to define the mechanisms by which PTK7 promotes vascular endothelial growth factor-A (VEGF-A)-induced angiogenesis in vivo and in vitro. Immunoblotting was used to measure PTK7 expression in several types of vascular endothelial cells. Using both immunoprecipitation and immunoblotting, PTK7 was found to join a receptor complex with Flt-1 (VEGFR1), but not with KDR/Flk-1 (VEGFR2) or with Flt-4 (VEGFR3). By surface plasmon resonance analysis, the interaction between Flt-1 and PTK7 was confirmed and found to be intensified by VEGF-A. Flt-1 phosphorylation and downstream signals of Akt, and focal adhesion kinase (FAK) thus induced were down-regulated by inhibition of PTK7 expression using siRNA. Moreover, PTK7 overexpression in endothelial cells resulted in enhanced angiogenesis in vitro. In contrast, neovascularization induced in vivo by VEGF-A pellets was significantly decreased by injection of siRNA targeting PTK7. These data suggest that PTK7 serves an essential role in Flt-1-mediated angiogenesis.

A novel pro-lymphangiogenic function for Th17/IL-17.

Th17 cells, in addition to their proinflammatory functions, have been recognized as potent inducers of angiogenesis in autoimmune diseases and malignancies. In the present study, we demonstrate distinct mechanisms by which IL-17 induces lymphangiogenesis. Using the mouse cornea micropocket and cell culture assays, our data demonstrate that IL-17 directly promotes growth of lymphatic vessels by inducing increased expression of prolymphangiogenic VEGF-D and proliferation of lymphatic endothelial cells. However, IL-17-induced growth of blood vessels is primarily mediated through IL-1ß secretion by IL-17-responsive cells. Furthermore, in vivo blockade of IL-17 in a preclinical model of Th17-dominant autoimmune ocular disease demonstrates a significant reduction in the corneal lymphangiogenesis and in the progression of clinical disease. Taken together, our findings demonstrate a novel prolymphangiogenic function for Th17/IL-17, indicating that IL-17 can promote the progression and amplification of immunity in part through its induction of lymphangiogenesis.

Clinical Outcomes of Descemet Membrane Endothelial Keratoplasty Using a Preloaded Imported Graft.

PURPOSE: Although the popularity of Descemet membrane endothelial keratoplasty (DMEK) is increased, there is still few clinical studies in Korea. In this study, we aimed to report the initial clinical outcomes of DMEK in patients followed up for more than 6 months. METHODS: A total of 96 eyes that underwent DMEK by a single surgeon for Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy, or other indications were evaluated for best-corrected visual acuity (BCVA), endothelial cell density (ECD), central corneal thickness (CCT), postoperative complications, and graft survival. RESULTS: The postoperative BCVA significantly increased compared to the preoperative BCVA by 59.4% (1.00 ± 0.77 logarithm of the minimum angle of resolution vs. 0.67 ± 0.76 logarithm of the minimum angle of resolution, p < 0.001). The average preoperative ECD was 754 ± 382 cells/mm2, increasing to 1,333 ± 562 cells/mm2 at 3 months (76.8%, p < 0.001), 1,334 ± 632 cells/mm2 at 6 months (76.9%, p < 0.001), 1,121 ± 474 cells/mm2 at 12 months (48.7%, p = 0.024), and 972 ± 458 cells/mm2 at 24 months postoperatively (28.9%, p = 0.445). Compared to 3 months, the ECD declined by 15.9% at 12 months (p = 0.009) and 27.1% at 24 months postoperatively (p = 0.158). The average CCT was 675 ± 113 µm preoperatively, decreasing to 581 ± 102, 574 ± 101, and 594 ± 94 µm at 6, 12, and 24 months after DMEK, respectively (p < 0.001 between all follow-up time points). Allograft rejection was detected in three (3.1%) and 14 eyes (14.6%) underwent retransplantation at an average of 10.1 ± 8.4 months after DMEK. CONCLUSIONS: DMEK is promising for maintaining corneal clarity, low postoperative complication rates, and stable graft longevity.

Long-Term Follow-Up of Corneal Endothelial Cell Changes After Iris-Fixated Phakic Intraocular Lens Explantation.

PURPOSE: The purpose of this study was to evaluate long-term corneal endothelial cell changes and visual outcomes after iris-fixated phakic intraocular lens (pIOL) explantation in patients with endothelial damage and to investigate potential predictors of endothelial injury. METHODS: Consecutive patients undergoing pIOL explantation with corneal endothelial cell density (ECD) <2000 cells/mm 2 at the time of the procedure were retrospectively reviewed in a single tertiary center. All patients were treated between April 2016 and October 2020 at a high-volume referral-based tertiary hospital. The primary outcome was the change in corneal endothelial parameters, including ECD, over long-term follow-up. Secondary outcomes included changes in corrected distance visual acuity and analysis of prognostic factors. RESULTS: This study included 44 eyes from 28 patients with an average age of 42.5 ± 7.8 years (range: 27-63). Mean ECD before explantation was 1375.4 ± 468.2 cells/mm 2 (range: 622-1996), and the average duration of follow-up after explantation was 20.5 months (6-58.2). Two years after explantation, ECD had significantly decreased by more than 25% to 1019.6 ± 368.6 (608-1689; P < 0.01). However, there was no significant change in corrected distance visual acuity (20/23-20/22, P = 0.59). Longer operation duration (odds ratio, 1.004; P = 0.04) was the only significant factor weakly associated with postoperative decreases in ECD. CONCLUSIONS: Although ECD continuously decreased despite pIOL explantation on a long-term follow-up, patients did not experience any discomfort or showed decreases in visual acuity. Therefore, a careful follow-up is required for possible endothelial injury after pIOL explantation.