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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.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.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; P0.01). 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.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.

Figure S1: Gene ontology analysis of up-regulated and down-regulated differentially expressed proteins in each retinal region.; Table S1: List of differentially expressed proteins in each retinal region after myopia induction.

Bioresponsive hydrogels are smart materials that respond to various external stimuli and exhibit great potential as biosensors owing to their capability of real-time and label-free detection. Here, we propose a sensing platform based on bioresponsive hydrogels, employing the concept of moiré patterns. Two sets of line patterns with different pitch sizes are prepared; a hydrogel grating whose pitch size changes according to external stimuli and a reference grating with constant pitch size. The volume changes of the hydrogel caused by external stimuli changes the pitch size of the hydrogel grating, and subsequently, the pitch sizes of the moiré patterns (moiré signal), whose values can be obtained in a real-time and label-free manner through customized moiré microscopy and signal processing. After confirming that the pH-induced swelling of hydrogel could be monitored using moiré patterns, we performed moiré pattern-based detection of specific proteins using protein-responsive hydrogel that underwent shrinking via interaction with target proteins. Brain-derived neurotrophic factor and platelet-derived growth factor were selected as the model proteins, and our proposed system successfully detected both proteins at nanomolar levels. In both cases, the pitch size change of hydrogel grating was monitored much more sensitively using moiré patterns than through direct measurements. The changes in the moiré signals caused by target proteins were detected in

Background/aimsTo evaluate subtypes and characteristics of dry eye (DE) using conventional tests and dynamic tear interferometry, and to investigate determinants of disease severity in each DE subtype.Methods309 patients diagnosed with DE and 69 healthy controls were prospectively enrolled. All eyes were evaluated using Ocular Surface Disease Index (OSDI), Schirmer’s test I (ST1) and Meibomian gland dysfunction (MGD) grade were analysed. The tear interferometric pattern and lipid layer thickness were determined using DR-1α and LipiView II, respectively.ResultsDynamic interferometric analysis revealed 56.6% of patients with DE exhibited Jupiter patterns, indicative of aqueous-deficiency, while 43.4% exhibited crystal patterns, indicative of lipid deficiency. These findings were in accordance with classification based on ST1 scores and MGD grade. Conventional assessment indicated 286 patients exhibited evidence of evaporative DE (EDE) due to MGD, while only 11 exhibited signs of pure aqueous-deficient DE (pure ADDE, only ST1 ≤5 mm). Interestingly, of 286 patients with EDE, 144 were categorised into the mixed-ADDE/EDE group, in which ST1 was identified as a strong negative determinant of OSDI. In contrast, 72.2% of patients with mixed-ADDE/EDE exhibited Jupiter patterns (Jupiter mixed), while 27.8% exhibited crystal patterns (crystal mixed). OSDI values were significantly higher in the crystal-mixed group than in the Jupiter mixed, in which OSDI scores were independently associated with ST1 values only.ConclusionsOur findings indicate that majority of EDE patients also exhibit aqueous deficiency, which can aggravate symptoms even in patients with lipid-deficient mixed-ADDE/EDE. Conventional assessments should be combined with interferometric tear analysis to determine the most appropriate treatment for each DE patient.

Human breast milk (HBM)-derived exosomes contain various biological and immunological components. However, comprehensive immune-related and antimicrobial factor analysis requires transcriptomic, proteomic, and multiple databases for functional analyses, and has yet to be conducted. Therefore, we isolated and confirmed HBM-derived exosomes by detecting specific markers and examining their morphology using western blot and transmission electron microscopy. Moreover, we implemented small RNA sequencing and liquid chromatography-mass spectrometry to investigate substances within the HBM-derived exosomes and their roles in combating pathogenic effects, identifying 208 miRNAs and 377 proteins associated with immunological pathways and diseases. Integrated omics analyses identified a connection between the exosomal substances and microbial infections. In addition, gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway analyses demonstrated that HBM-derived exosomal miRNA and proteins influence immune-related functions and pathogenic infections. Finally, protein–protein interaction analysis identified three primary proteins (ICAM1, TLR2, and FN1) associated with microbial infections mediating pro-inflammation, controlling infection, and facilitating microbial elimination. Our findings determine that HBM-derived exosomes modulate the immune system and could offer therapeutic strategies for regulating pathogenic microbial infection.

Recent studies have demonstrated that the oral microbiome in patients with Sjögren’s syndrome (SS) is significantly different from that in healthy individuals. However, the potential role of the oral microbiome in SS pathogenesis has not been determined. In this study, stimulated intraductal saliva samples were collected from the parotid glands (PGs) of 23 SS and nine non-SS subjects through PG lavage and subjected to 16S ribosomal RNA amplicon sequencing. The correlation between the oral microbiome and clinical features, such as biological markers, clinical manifestations, and functional and radiological characteristics was investigated. The salivary microbial composition was examined using bioinformatic analysis to identify potential diagnostic biomarkers for SS. Oral microbial composition was significantly different between the anti-SSA-positive and SSA-negative groups. The microbial diversity in SS subjects was lower than that in non-SS sicca subjects. Furthermore, SS subjects with sialectasis exhibited decreased microbial diversity and Firmicutes abundance. The abundance of Bacteroidetes was positively correlated with the salivary flow rate. Bioinformatics analysis revealed several potential microbial biomarkers for SS at the genus level, such as decreased Lactobacillus abundance or increased Streptococcus abundance. These results suggest that microbiota composition is correlated with the clinical features of SS, especially the ductal structures and salivary flow, and that the oral microbiome is a potential diagnostic biomarker for SS.

Uncovering region-specific changes in the myopic retina can provide clues to the pathogenesis of myopia progression. After imposing form deprivation myopia in the right eye of 6-week-old rabbits, we investigated the proteome profile of each retinal region (central, mid-periphery, and far-periphery retina), using accurate high-resolution mass spectrometry. Protein expression was analyzed using gene ontology and network analysis compared with that of the control, the left eyes. Among 2065 proteins detected from whole retinal samples, 249 differentially expressed proteins (DEPs) were identified: 164 DEPs in the far-periphery, 39 in the mid-periphery, and 83 in the central retina. In network analysis, the far-periphery retina showed the most significant connectivity between DEPs. The regulation of coagulation was the most significant biological process in upregulated DEPs in the far-periphery retina. Proteasome was the most significant Kyoto Encyclopedia of Genes and Genomes pathway in downregulated DEPs in the central retina. Antithrombin-III, fibrinogen gamma chain, and fibrinogen beta chain were identified as hub proteins for myopia progression, which were upregulated in the far-periphery retina. Proteomic analysis in this study suggested that oxidative stress can be the primary pathogenesis of myopia progression and that the far-periphery retina plays a role as the key responder.

To determine the relationship between tear film interferometric patterns and properties of lipid, including rheological properties.Prospective, cross-sectional laboratory investigation.This study included 105 subjects (94 dry eye patients and 11 normal participants). The subjects were divided into 3 categories (group 1, normal; group 2, thin; and group 3, irregular) according to interferometric patterns. According to tear interferometric patterns, ultra-performance liquid chromatography (LC) quadrupole-linear ion trap/mass spectrometry (MS)-based analysis was used to investigate lipid profiling of meibum. Rheological properties were examined by using a Langmuir-Blodgett trough with saline solution.Normal subjects showed Pearl-like patterns, and dry eye patients showed either irregular or thin patterns. Group 2 tended to be the evaporative type, and group 3 tended to be the aqueous-deficient type. Lipid profiling using LC-MS identified 280 lipid species of 25 lipid classes. In the meibum of the patient groups, the content of cholesteryl esters and nonpolar lipids was lower than that in the normal group. However, the content of polar lipids such as sphingolipids and phospholipids in the patient groups was higher than that in the normal group. Rheological properties showed that the lift-off areas were comparable among the 3 groups and the surface tension was the highest in group 1, followed by group 3 and group 2.The findings of this study suggest that tear interferometric patterns are associated with lipid profiling of meibum and its rheological properties. These results may contribute toward the development of new treatment modalities.

Purpose: To evaluate the effectiveness of different treatment modalities for dry eye in primary Sjögren’s syndrome with their potential overlapping influences. Methods: This study included 199 patients with newly diagnosed primary Sjögren’s syndrome from 2005 to 2020. Various treatment modalities for primary Sjögren’s syndrome were compared. Improvement of corneal staining based on Sjögren’s International Collaborative Clinical Alliance (SICCA) scores was the primary outcome. Results: The average follow-up period was 5.4 ± 3.1 (range, 2.0–14.1) years. Analysis of the individual treatments showed that punctal plug insertions in the lower and upper eyelids were strongly associated with improvement of SICCA scores (β = 2.70 and 1.80, p < 0.001 and

To evaluate the effects of meibomian gland dysfunction (MGD) and aqueous deficiency (AD) on friction-related disease (FRD).Cross-sectional comparative study. This study included 550 eyes (550 patients) with dry eye disease (DED). The DED subtype and dynamic tear-film parameters by automated assessments were investigated for the analysis of FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy).Patients with FRD had a higher proportion of moderate-to-severe MGD and AD (p 0.001 and p 0.001, respectively). The dropout rate of the meibomian gland was higher (30.5 ± 31.8 and 14.1 ± 25.0%, p 0.001), tear meniscus height (TMH) was lower (227.8 ± 60.4 and 241.7 ± 55.6 μm, p = 0.008), and he first non-invasive keratographic tear break-up time (NIKBUT-1) was shorter (5.9 ± 3.5 and 7.3 ± 3.7 s, p 0.001) in patients with FRD than in those without FRD. In the logistic regression analysis with clinical manifestation, both moderate-to-severe MGD and AD were associated with FRD (odds ratios [OR] 12.27, 95% confidence interval [CI] 7.72-19.50, and 2.31, 95% CI 1.43-3.71], p 0.001 and p 0.001, respectively). The dropout rate was positively associated with FRD (OR 1.017, 95% CI 1.010-1.023, p 0.001). TMH and NIKBUT-1 were negatively associated with FRD (OR 0.995, 95% CI 0.991-0.999, and 0.90, 95% CI 0.85-0.95, p = 0.039 and p 0.001, respectively).This study showed that FRD was highly associated with MGD and meibomian gland dropout rate, suggesting that FRD may be mainly affected by lipid components. AD and TMH also had a good but relatively lower association with FRD, compared to MGD and meibomian gland dropout rate.

Methods of the early detection of diseases are based on recognition of the smallest change in the levels of a disease-specific biomarker in body fluids. Among them, monitoring protein concentrations is crucial because most diseases are caused by dysregulated protein levels, rather than DNA or RNA levels. Recent studies have indicated that the proteins in the aqueous humor can be used as biomarkers to predict brain diseases. Therefore, mounting an insertion type sensor on the intraocular lens is a compelling candidate platform for monitoring potential brain disease patients. In particular, molecular reactive sensors that use affinity binding, such as molecularly imprinted hydrogels, allow simple label-free detection, as well as high bio-applicability and biocompatibility. Herein, we describe the fabrication of an optical sensor using a silica nanoparticle conjugated bioresponsive hydrogel to analyze protein biomarkers by measuring light interference in smartphone images. Conformational changes in biotin-conjugated hydrogels were observed through the presence of avidin, as a substitution for a novel biomarker, in interconnecting hydrogel networks. Uniformly arrayed nanoparticles interfered with light differently when the distance between the silica nanoparticles was varied according to target moiety binding. A blue-shift of the reflected light was evident in avidin solutions of up to 100 nM and was induced by shrinkage of the hydrogel. The results indicate that our well-defined, label-free bioresponsive hydrogel demonstrated strong potential to be widely applied as a bioresponsive light interfering hydrogel sensor.

Purpose Comparison of the parasympathetic and sympathetic neurons, including the dopaminergic neural system, in dry eye (DE)-induced pathophysiology has not been elucidated well. This study investigated the presence of dopamine receptors (DRs) and their functional roles in the lacrimal glands (LGs) of DE-induced mice. Methods After DE was induced in B6 mice for 2 weeks, the expression of tyrosine hydroxylase (TH), dopamine, and DRs (DR1, DR2, etc.) in the LGs and corneas were measured by quantitative RT-PCR, immunoblot, and ELISA. Using flow cytometry and ELISA, immune cell infiltration and inflammatory cytokine expression were determined in DE-induced LGs with or without DR blockers, SCH-23390 (DR1i), or melperone (DR2i). Corneal erosion scores were also investigated. Results The mRNA and protein levels of TH significantly increased in DE-induced LGs. The dopamine concentration of LGs was 9.51 pmol in DE (versus naive: 1.39 pmol; P < 0.001). Both DR1 and DR2 mRNA expression were significantly enhanced in desiccating stress compared with those in naive (3.7- and 2.1-fold, P < 0.001). Interestingly, DR1 and DR2 immunostaining patterns stained independently in DE-induced LGs. CD3+ and CD19+ cell infiltration was significantly increased by DR2i (P < 0.001) but not by DR1i. Furthermore, IFN-γ, IL-17, and TNF-α were significantly upregulated by DR2i compared with the blow-only condition. The severity of corneal erosion and inflammation was also aggravated by DR2i. Conclusions Upregulation of DR1 and DR2 was observed in DE-induced mouse LGs. As the inflammatory conditions are aggravated by the inhibition of DRs, especially DR2, their activity may be an important factor preserving ocular surface homeostasis.

We investigated the clinical and genetic features of patients with severe phenotype of granular corneal dystrophy type 2 (GCD2) associated with compound heterozygosity in the transforming growth factor-β-induced (TGFBI) gene. Patients with severe GCD2 underwent ophthalmic examination (best-corrected visual acuity test, intraocular pressure measurement, slit-lamp examination, and slit-lamp photograph analysis) and direct Sanger sequencing of whole-TGFBI. The patient’s family was tested to determine the pedigrees. Five novel mutations (p.(His174Asp), p.(Ile247Asn), p.(Tyr88Cys), p.(Arg257Pro), and p.(Tyr468*)) and two known mutations (p.(Asn544Ser) and p.(Arg179*)) in TGFBI were identified, along with p.(Arg124His), in the patients. Trans-phase of TGFBI second mutations was confirmed by pedigree analysis. Multiple, extensive discoid granular, and increased linear deposits were observed in the probands carrying p.(Arg124His) and other nonsense mutations. Some patients who had undergone phototherapeutic keratectomy experienced rapid recurrence (p.(Ile247Asn) and p.(Asn544Ser)); however, the cornea was well-maintained in a patient who underwent deep anterior lamellar keratoplasty (p.(Ile247Asn)). Thus, compound heterozygosity of TGFBI is associated with the phenotypic variability of TGFBI corneal dystrophies, suggesting that identifying TGFBI second mutations may be vital in patients with extraordinarily severe phenotypes. Our findings indicate the necessity for a more precise observation of genotype–phenotype correlation and additional care when treating TGFBI corneal dystrophies.

Matrigel, a mouse tumor extracellular matrix protein mixture, is an indispensable component of most organoid tissue culture. However, it has limited the utility of organoids for drug development and regenerative medicine due to its tumor-derived origin, batch-to-batch variation, high cost, and safety issues. Here, we demonstrate that gastrointestinal tissue-derived extracellular matrix hydrogels are suitable substitutes for Matrigel in gastrointestinal organoid culture. We found that the development and function of gastric or intestinal organoids grown in tissue extracellular matrix hydrogels are comparable or often superior to those in Matrigel. In addition, gastrointestinal extracellular matrix hydrogels enabled long-term subculture and transplantation of organoids by providing gastrointestinal tissue-mimetic microenvironments. Tissue-specific and age-related extracellular matrix profiles that affect organoid development were also elucidated through proteomic analysis. Together, our results suggest that extracellular matrix hydrogels derived from decellularized gastrointestinal tissues are effective alternatives to the current gold standard, Matrigel, and produce organoids suitable for gastrointestinal disease modeling, drug development, and tissue regeneration.

Background: Mutations of the transforming growth factor-β-induced (TGFBI) gene produce various types of corneal dystrophy. Here, we report a novel de novo L509P mutation not located in a known hot spot of the transforming growth factor-β-induced (TGFBI) gene and its clinical phenotype, which resembles that of lattice corneal dystrophy type IIIA (LCD IIIA). Case presentation: A 36-year-old man (proband) visited our clinic due to decreased visual acuity with intermittent ocular irritation in conjunction with painful recurrent erosions in both eyes for 10 years. Molecular genetic analyses revealed a TGFBI L509P mutation (c.1526T>C) in the proband and one of his sons. Interestingly, neither TGFBI mutations nor corneal abnormalities were detected in either of the proband’s biological parents, indicating the occurrence of a de novo L509P mutation. Clinical examinations, including slit-lamp retro-illumination and Fourier-domain anterior segment optical coherence tomography (FD-OCT), revealed gray deposits in the anterior stroma and deeper refractile lines extending from limbus to limbus in both corneas of the proband, consistent with a diagnosis of LCD IIIA. Superficial diffuse haze and surface irregularity were observed in conjunction with corneal erosions and visual impairment, necessitating phototherapeutic keratectomy (PTK). A 60 μm PTK of the Bowman layer and anterior stroma of the proband’s left eye was performed following the removal of the epithelium in order to remove superficial corneal opacities. His BCVA improved from 20/400 to 20/50 at postoperative week 8 and was maintained for 45 months. Pinhole-corrected VA was 20/20 at the last visit, and corneal opacities had not recurred. Conclusions: An inheritable de novo mutation of L509P in the TGFBI gene can produce severe LCD IIIA, which can be successfully treated with OCT-guided PRK.

Our previous studies have shown that heat-killed Lactobacillus sakei K040706 exerts immunostimulatory and anti-inflammatory activities in macrophages, cyclophosphamide (CYP)-treated mice, and dextran sulfate sodium&ndash, induced colitis mice. However, the immunostimulatory effects of live Lactobacillus sakei K040706 (live K040706) against CYP-induced immunosuppression and its underlying molecular mechanisms remain unknown. Therefore, we investigated the immunostimulatory effects of live K040706 (108 or 109 colony forming unit (CFU)/day, p.o.) in CYP-induced immunosuppressed mice. Oral administration of live K040706 prevented the CYP-induced decreases in body weight, thymus index, natural killer (NK) cell activity, T and B cell proliferation, and cytokine (interferon (IFN)-&gamma, interleukin (IL)-2, and IL-12) production. The administration of live K040706 also exerted positive effects on the gut microbiota of CYP-induced mice, resulting in a microbiota composition similar to that of normal mice. Moreover, live K040706 significantly enhanced IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) production in the splenocytes and Peyer&rsquo, s patch (PP) cells of mice and increased bone marrow (BM) cell proliferation. Taken together, our data indicate that live K040706 may effectively accelerate recovery from CYP-induced immunosuppression, leading to activation of the immune system. Therefore, live K040706 may serve as a potential immunomodulatory agent against immunosuppression.

Purpose To report cases of necrotizing scleritis, a sight-threatening complication that can result from cosmetic conjunctivectomy procedures. Design Retrospective case series. Methods The medical records of consecutive patients who underwent eye-whitening conjunctivectomy with mitoycin C (MMC) treatment performed by 1 surgeon in South Korea and were referred to the authors' clinic between January 2011 and December 2015 were reviewed. The patients in whom findings of necrotizing scleritis with active inflammation were detected in an avascular area of previous conjunctivectomy were included. Results Of a total of 231 patients who had received cosmetic eye whitening, 4 patients who met the inclusion criteria were identified. The average length of time from cosmetic eye surgery to a diagnosis of necrotizing scleritis was 51 months and all patients had unilateral findings of necrotizing scleritis. There was no underlying systemic autoimmunity or infectious etiology in all cases. Three of these 4 patients were treated with a conjunctival flap; however, all 4 received systemic anti-inflammatory treatment with oral corticosteroids. The mean follow-up duration of the patients was 22.75 months. Conclusions Necrotizing scleritis is a severe complication that can arise after cosmetic eye-whitening conjunctivectomy with MMC. Because of the large area of the ocular surface that is treated in eye-whitening with MMC, the necrotizing scleritis that can ensue may be more extensive and severe than the surgically induced necrotizing scleritis following other periocular surgeries such as pterygium removal. Proper anti-inflammatory treatment and surgical intervention should be required for management of this complication.

Purpose While the normal cornea has limited innervation by the lymphatic system, chronic immune-inflammatory disorders such as dry eye (DE) can induce lymphangiogenesis in the ocular surface. Using a conditional knock-down murine model, Lyve-1 Cre ;VEGFR2 flox mice, this study investigated the role of lymphangiogenesis in the pathophysiology of DE. Methods DE was induced in both wild type (WT) B6 and Lyve-1 Cre ;VEGFR2 flox mice. Tissue immunostaining and volumetric gross measurements were used to assess changes in the ocular surface, skin, and lymph nodes (LNs). The expression of lymphangiogenic factors (TNF-α, IL-6/-8/-12/-17, VEGF-C/-D, IFN-γ, VEGFR-2/-3, Lyve-1, and podoplanin) and the frequency of immune cells (CD4, CD11b, and CD207) on the ocular surface and lacrimal glands were quantified by real-time polymerase chain reaction and flow cytometry. Results Compared to WT mice, there were fewer lymphatic vessels and a reduction in lymphangiogenic markers in the ocular surface and skin of Lyve-1 Cre ;VEGFR2 flox mice. After DE induction, mRNA levels of TNF-α, IL-8, and IFN-γ were significantly reduced in Lyve-1 Cre ;VEGFR2 flox mice compared to WT mice ( p Cre ;VEGFR2 flox mice with DE were significantly smaller and populated by fewer dendritic cells and effector T cells than those from WT mice ( p Cre ;VEGFR2 flox mice were notably intact like in the naive condition. Conclusions Inhibition of lymphangiogenesis in the cornea effectively attenuates not only the inflammatory response including trafficking of immune cells but also preserves corneal nerves under desiccating stress. Corneal lymphangiogenesis might be a contributing factor in deterioration on the ocular surface homeostasis.

To investigate the influence of periocular radiotherapy on meibomian glands.We evaluated 28 patients (40 eyes) who received radiotherapy (RT group) for conjunctival or orbital lymphoma and 30 age-matched control subjects (60 eyes). Subjects underwent slit-lamp examination of the eyelids, Schirmer test, meibography, and evaluation of tear film breakup time (TBUT), Ocular Surface Disease Index (OSDI) scores, meibomian glands evaluation (meiboscore, meibum expressibility, and lid margin abnormality scores), and tear film lipid layer thickness using an ocular surface interferometer. These parameters were compared between subjects in the RT and control groups.Meiboscores as well as meibum expressibility and OSDI scores in the RT group were significantly higher compared with those in the control group (1.6 ± 0.9 vs. 0.4 ± 0.6, 1.6 ± 1.0 vs. 0.2 ± 0.4, and 48.1 ± 21.4 vs. 6.2 ± 4.4, respectively, P0.001, all), whereas the Schirmer value (9.2 ± 5.1 vs. 12.3 ± 5.2, P = 0.004), TBUT (4.2 ± 2.5 vs. 6.4 ± 2.6, P = 0.001), and lipid layer thickness (61.0 ± 29.3 vs. 85.2 ± 20.0, P0.001) in the RT group were lower compared with those in the control group. The percentage of meibomian gland dropout was significantly correlated with age (P = 0.025) and total radiation dose (P = 0.012), regardless of the target location of irradiation. Even low-dose irradiated eyes (30 Gy) exhibited significantly higher meiboscores (P0.001) and shorter TBUT (P = 0.005) compared with control eyes.Eyes that received periocular radiotherapy exhibited relatively high tear film instability induced by meibomian gland dysfunction, contributing to the high severity of dry eye symptoms.

Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED), and in severe cases can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease. Acinar cells of the lacrimal glands, not inflammatory immune cells, are the primary source of IL-22, which suppresses inflammation in ocular surface epithelial cells upon desiccating stress. Moreover, loss of function analyses using IL-22 knock-out mice demonstrated that IL-22 is essential for suppression of ocular surface infiltration of Th17 cells and inhibition of DED induction. Our novel findings elucidate immunoregulatory function of lacrimal gland-derived IL-22 in inhibiting IL-17-mediated ocular surface epitheliopathy in DED thus making IL-22 a new relevant therapeutic target.

Previously, we first reported the identification of four p-coumaroyl anthocyanins (petanin, peonanin, malvanin, and pelanin) from the tuber epidermis of colored potato (Solanum tuberosum L. cv JAYOUNG). In this study, we investigated the anti-oxidative and anti-inflammatory effects of a mixture of peonanin, malvanin, and pelanin (10 : 3 : 3; CAJY). CAJY displayed considerable radical scavenging capacity of 1, 1-diphenyl-2-picryl-hydrazyl (DPPH), increased mRNA levels of the catalytic and modulatory subunit of glutamate cysteine ligase, and subsequent cellular glutathione content. These increases preceded the inhibition of lipopolysaccharide (LPS)-induced intracellular reactive oxygen species (ROS) production. CAJY inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a concentration-dependent manner at the protein, mRNA, and promoter activity levels. These inhibitions caused attendant decreases in the production of prostaglandin E2 (PGE2). CAJY suppressed the production and mRNA expression of tumor necrosis factor (TNF)-α and interleukin (IL)-6. Molecular data revealed that CAJY inhibited the transcriptional activity and translocation of nuclear factor κB (NF-κB) and phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3. Taken together, these results suggest that the anthocyanin mixture exerts anti-inflammatory effects in macrophages, at least in part by reducing ROS production and inactivating NF-κB and STAT 1/3.

The eye is an extension of the central nervous system (CNS) and contains aqueous humor (AH), which is a fluid rich in biomolecules secreted from intraocular tissues; thus, this organ allows for non-invasive visualization of early changes in CNS disorders. There is a growing interest in developing implantable devices, such as intraocular-lens (IOL), for specific medical uses, including intraocular monitoring. We describe a novel IOL-sensing system for detecting AH biomarkers via biocompatible enzyme-activatable fluorogenic hydrogel sensors. Matrix-metalloproteinase-9, a biomarker of degenerative CNS and eye disorders, was selected as a target. A peptide-probe-incorporated fluorogenic IOL (FIOL) was developed using diacrylamide-group-modified poly(ethyleneglycol) (PEGDAAm) biocompatible hydrogels, adjusting the hydrogel mesh size to allow selective penetration of the target while blocking non-targets, using label-free detection with semi-permanently implantable sensors, and demonstrating the clinical feasibility of FIOL through in vivo testing. This novel FIOL-based sensing system represents a promising approach for liquid biopsy of intraocular fluids.

Purpose To compare the changes in human tear proteome and clinical effects following topical cyclosporine A (CsA) 0.05% or diquafosol tetrasodium (DQS) 3% treatment of dry eye disease (DED), and to identify biomarkers for determining disease severity and treatment effectiveness in DED. Methods A total of 18 patients were diagnosed with non-Sjogren DED. Nine patients in each group were treated with topical CsA 0.05% or DQS 3% for 4 weeks. Tear samples were collected after evaluation of tear breakup time, corneal and conjunctival erosion staining, and results of Schirmer's test 1 before and after treatment. Proteomes were characterized using liquid chromatography mass spectrometry, and proteins exhibiting a fold change >1.5 or

Transforming growth factor beta-induced (TGFBI) corneal dystrophies are a group of inherited progressive corneal diseases. Accumulation of transforming growth factor beta-induced protein (TGFBIp) is involved in the pathogenesis of TGFBI corneal dystrophies; however, the exact molecular mechanisms are not fully elucidated. In this review article, we summarize the current knowledge of TGFBI corneal dystrophies including clinical manifestations, epidemiology, most common and recently reported associated mutations for each disease, and treatment modalities. We review our current understanding of the molecular mechanisms of granular corneal dystrophy type 2 (GCD2) and studies of other TGFBI corneal dystrophies. In GCD2 corneal fibroblasts, alterations of morphological characteristics of corneal fibroblasts, increased susceptibility to intracellular oxidative stress, dysfunctional and fragmented mitochondria, defective autophagy, and alterations of cell cycle were observed. Other studies of mutated TGFBIp show changes in conformational structure, stability and proteolytic properties in lattice and granular corneal dystrophies. Future research should be directed toward elucidation of the biochemical mechanism of deposit formation, the relationship between the mutated TGFBIp and the other materials in the extracellular matrix, and the development of gene therapy and pharmaceutical agents.

Purpose The purpose of this study was to investigate the expression of death ligands in the lacrimal glands (LGs), identify upstream factors that regulate their expression, and determine the functional roles of these factors in the pathogenesis of dry eye disease (DED). Methods For DED experiment, ex vivo coculture system with LG and in vivo murine model using a controlled environment chamber were utilized. C57BL/6 mice and hypoxia-inducible factor (HIF)-1α conditional knockout (CKO) mice were used. Immunohistochemical staining, polymerase chain reaction, and immunoblotting were performed to determine levels of death ligands including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in DED-induced LGs. Additionally, acinar cell and CD45+ cell apoptosis was determined with neutralizing TRAIL treatment. Results Desiccating stress significantly increased HIF-1α expression in LG-acinar cells. Furthermore, HIF-1α deficiency significantly enhanced the infiltration of CD45+ inflammatory cells in LG and induced LG-acinar cell death. Meanwhile, only TRAIL expression was increased in DED-LG, but abrogated in HIF-1α CKO. Interestingly, the main source of TRAIL was the CD45- LG-acinar cells, but not CD45+ immune cells after DED induction. Using ex vivo coculture system, we confirmed LG-induced apoptosis of immune cells via HIF-1α-mediated TRAIL secretion following DED. Consistent with ex vivo, the insufficiency of HIF-1α and TRAIL enhanced recruitment of inflammatory cells to the LG and subsequently exacerbated ocular surface damage in DED mice. Conclusions Our findings offer novel insight into the regulatory function of acinar cell-derived TRAIL in limiting inflammatory damage and could be implicated in the development of potential therapeutic strategies for DED.

Alzheimer's disease (AD) is an ageing-related neurodegenerative disease characterized and diagnosed by deposition of insoluble amyloid-β (Aβ) plaques in the brain. The plaque accumulation in the brain directly affects reduced levels of Aβ in cerebrospinal fluid (CSF) and blood, as Aβ can freely transport the blood-brain barrier, and clinical investigations have suggested these two biofluids as promising samples for in vitro diagnosis. Given that the human eye structurally resembles the brain and Aβ accumulation often observed in the ocular region of AD patients, in this study, we examined aqueous humor Aβ as another possible surrogate biomarker. First, using the acute Aβ-infused AD mouse model by injecting Aβ to the CSF in intracerebroventricular region of normal ICR mice, we investigated whether Aβ concentration in the aqueous humor in AD models is positively correlated with the concentration in the CSF. Then, we examined the correlation of aqueous humor Aβ levels with increased plaque deposition in the brain and reduced Aβ levels in both CSF and blood in adult and aged 5XFAD Alzheimer transgenic mice. Collectively, the synthetic Aβ injected into CSF immediately migrate to the aqueous humor, however, the age-dependently reducing pattern of Aβ levels in CSF and blood was not observed in the aqueous humor.

To determine the mucinogenic effect of dry eye (DE) treatment drugs currently in use, we compared the levels of mucin production and inflammatory cytokine expression on the ocular surfaces using a DE-induced mice model.C57BL/6 mice were separated into 6 groups: a control group, DE-induced mice with the vehicle and treated with cyclosporine A (CsA), rebamipide (Reb), diquafosol tetrasodium (DQS), or prednisolone (Pred). The mRNA expression of MUC 1, 4, 16, 5AC, and proinflammatory cytokines on the corneal epithelia were determined by quantitative real-time polymerase chain reaction. Expression of each MUC was evaluated using flow cytometry and immunohistostaining. Conjunctival goblet cells were analyzed through periodic acid-Schiff (PAS) staining.Desiccating stress significantly decreased both mRNA and protein levels of all MUCs in the cornea. CsA mainly enhanced MUC5AC, with an increase in PAS-positive cells, whereas DQS chiefly increased membrane-associated mucins (MM). However, Reb only minimally increased expression of MUC5AC and Pred only increased MUC4. MUC16 did not show any significant change in any group. On the contrary, the mRNA levels of interleukin (IL)-1β, -6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were increased in the DE corneas of the control mice and were reduced by all treatments; in particular, IL-6 was significantly suppressed.Topical DQS and CsA not only ameliorated ocular surface inflammation under desiccating stress but also upregulated both MM and secretory mucins (SM) and contributed to conjunctival goblet cell recovery, compared to Reb and Pred. Both anti-inflammatory and secretory factors should be considered simultaneously when measuring the treatment effect of DE drugs.

To compare objective accommodation of phakic and pseudophakic eyes between two different age groups. Eighty-three eyes (83 participants aged ≥ 40 years) with a visual acuity of 20/25 or better, and refractive error < spherical − 1.0 diopters (D) and cylindrical 1.0 D, were included. Forty-four patients had undergone phacoemulsification and monofocal intraocular lens implantation and were examined 6 months post-surgery. Participants were divided into groups 1 (pseudophakic, age

Purpose Normal-tension glaucoma (NTG) is a heterogenous disease, and there is still controversy about subclassifications of this disorder. On the basis of spectral-domain optical coherence tomography (SD-OCT), we subdivided NTG with hierarchical cluster analysis using optic nerve head (ONH) parameters and retinal nerve fiber layer (RNFL) thicknesses. Patients and methods A total of 200 eyes of 200 NTG patients between March 2011 and June 2012 underwent SD-OCT scans to measure ONH parameters and RNFL thicknesses. We classified NTG into homogenous subgroups based on these variables using a hierarchical cluster analysis, and compared clusters to evaluate diverse NTG characteristics. Results Three clusters were found after hierarchical cluster analysis. Cluster 1 (62 eyes) had the thickest RNFL and widest rim area, and showed early glaucoma features. Cluster 2 (60 eyes) was characterized by the largest cup/disc ratio and cup volume, and showed advanced glaucomatous damage. Cluster 3 (78 eyes) had small disc areas in SD-OCT and were comprised of patients with significantly younger age, longer axial length, and greater myopia than the other 2 groups. Conclusions A hierarchical cluster analysis of SD-OCT scans divided NTG patients into 3 groups based upon ONH parameters and RNFL thicknesses. It is anticipated that the small disc area group comprised of younger and more myopic patients may show unique features unlike the other 2 groups.

Previously, we first reported the identification of four p-coumaroyl anthocyanins (petanin, peonanin, malvanin, and pelanin) from the tuber epidermis of colored potato (Solanum tuberosum L. cv JAYOUNG). In this study, we investigated the anti-oxidative and anti-inflammatory effects of a mixture of peonanin, malvanin, and pelanin (10 : 3 : 3; CAJY). CAJY displayed considerable radical scavenging capacity of 1, 1-diphenyl-2-picryl-hydrazyl (DPPH), increased mRNA levels of the catalytic and modulatory subunit of glutamate cysteine ligase, and subsequent cellular glutathione content. These increases preceded the inhibition of lipopolysaccharide (LPS)-induced intracellular reactive oxygen species (ROS) production. CAJY inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in a concentration-dependent manner at the protein, mRNA, and promoter activity levels. These inhibitions caused attendant decreases in the production of prostaglandin E

To understand the pathophysiology of dry eye disease (DED), it is necessary to characterize proteins in the ocular surface fluids, including tear fluid (TF) and lacrimal fluid (LF). There have been several reports of TF proteomes, but few proteomic studies have examined LF secreted from the lacrimal gland (LG). Therefore, we characterized the proteins constituting TF and LF by liquid chromatography mass spectrometry. TF and LF were collected from patients with non-Sjögren syndrome DED and from healthy subjects. Through protein profiling and label-free quantification, 1165 proteins from TF and 1448 from LF were identified. In total, 849 proteins were present in both TF and LF. Next, candidate biomarkers were verified using the multiple reaction monitoring assay in both TF and LF of 17 DED patients and 17 healthy controls. As a result, 16 marker proteins were identified (fold-change > 1.5, p-value

PURPOSE To determine the effect of lowering femtosecond laser energy on the surface quality of the intrastromal interface during small incision lenticule extraction (SMILE). METHODS Forty age- and diopter-matched female patients (40 eyes) with moderate myopia received SMILE with different energy levels (100 to 150 nJ) and fixed spot separation (4.5 μm). Five human corneal lenticules from each energy group were evaluated by atomic force microscopy and scanning electron microscopy (SEM). Both anterior and posterior surface characteristics of the lenticules were assessed. RESULTS All measurements of surface roughness were approximately three times higher and in the anterior and posterior surface of the lenticules with the energy level of 150 nJ than with 100 nJ (P < .001). Furthermore, atomic force microscopy analysis found that energy differences of 15 nJ or more made a significant difference in surface roughness at energy levels of 115 nJ or higher. Interestingly, there was no significant difference in all roughness values of both surfaces among the 100, 105, and 110 nJ groups. In addition, all values of surface roughness were significantly positively correlated with laser energy for both anterior and posterior surfaces of the lenticule (P < .001). Consistent with atomic force microscopy results, SEM also showed that the SMILE lenticules in the higher laser energy group had more irregular surfaces. CONCLUSIONS Lowering laser energy levels can improve surface quality of the lenticule of SMILE. To achieve better visual outcomes with faster recovery after the procedure, it is recommended to reduce the laser energy to less than 115 nJ at a spot separation of 4.5 μm. [J Refract Surg. 2017;33(9):617-624.].

To determine the effect of lowering laser energy on clinical outcomes in small-incision lenticule extraction (SMILE).Prospective randomized clinical trial.A total of 151 patients (151 eyes) with moderate myopia scheduled for SMILE were included: 58 eyes received SMILE with low energy (100, 105, and 110 nJ; L-SMILE group) and 93 with conventional energy (115-150 nJ; C-SMILE group). Patients received complete ophthalmic examinations preoperatively and over 3 months postoperatively.Uncorrected distance visual acuity (logMAR UDVA) 1 day and 1 week postoperatively was significantly better in L-SMILE than in C-SMILE (P.001 and P = .005, respectively). There was no significant difference between the groups at 1 and 3 months. L-SMILE induced significantly fewer corneal aberrations compared with C-SMILE at 1 week and 1 month postoperatively (both P.01), but there were no significant differences at 3 months. Though there was no difference in logMAR UDVA over the postoperative period between the 100, 105, and 110 nJ subgroups, there was a significant difference in logMAR UDVA on postoperative day 1 between L-SMILE and each subgroup in which an energy level of 115 nJ or higher was used. Furthermore, logMAR UDVA on postoperative day 1 showed a significant correlation with laser energy (r = 0.451, P.001) and multiple linear regression analysis revealed that energy level was the only independent factor associated with logMAR UDVA on postoperative day 1 (P.001).SMILE using femtosecond energy of less than 115 nJ facilitates better visual acuity with less induction of corneal aberrations in the early postoperative period.

To investigate automated values from an advanced corneal topographer with a built-in real keratometer, color camera, and ocular surface interferometer for the evaluation of non-Sjögren dry eye syndrome (NSDES) with meibomian gland dysfunction (MGD).Sixty-four patients (64 eyes) diagnosed with NSDES with MGD were enrolled. All eyes were evaluated using the Ocular Surface Disease Index (OSDI), fluorescence staining score, tear film breakup time (TBUT), Schirmer test, and MGD grade. Noninvasive Keratograph average tear film breakup time (NIKBUTav), tear meniscus height (TMHk), meibomian gland (MG) dropout grade, and lipid layer thickness (LLT) using interferometry were measured.Among automated indexes, NIKBUTav (mean 7.68 ± 4.07 s) and the MG dropout grade (mean 1.0 ± 0.5) significantly correlated with the OSDI (mean 40.6 ± 22.9) (r = -0.337, P = 0.006; and r = 0.201, P = 0.023, respectively), as did all conventional indicators, except the Schirmer score (mean 9.1 ± 5.9 mm). TMHk (mean 0.21 ± 0.18 mm) had significant correlation with the Schirmer score, the staining score (mean 1.2 ± 0.7), TBUT (mean 3.8 ± 1.8 s), and NIKBUTav (r = 0.298, P = 0.007; r = -0.268, P = 0.016; r = 0.459, P0.001; and r = 0.439, P0.001, respectively), but not any MGD indicator, even the MG dropout grade. NIKBUTav showed significant correlations with all clinical parameters and other automated values, except the Schirmer score and LLT (mean 83.94 ± 20.82 nm) (all (Equation is included in full-text article.)≥ 0.25 and P0.01). The MG dropout grade highly correlated with all indexes except TMHk (all (Equation is included in full-text article.)≥ 0.25 and P0.05). LLT was significantly associated with TBUT, MGD grade (mean 2.0 ± 0.7), and MG dropout grade (r = 0.219, P = 0.047; r = -0.221, P = 0.039; and r = 0.433, P0.001, respectively), although it was not related to patient symptoms.Automated noninvasive measurements using an advanced corneal topographer and LLT measured with an ocular surface interferometer can be alternatives to conventional methods to evaluate tear conditions on the ocular surface; the former device can provide information about conformational MG changes in NSDES with MGD.

Background: Surgical lifting and scraping is a well-known treatment for epithelial ingrowth, but treatment for epithelial ingrowth on the centrally perforated laser in situ keratomileusis (LASIK) flap has not been well studied. Case presentation: We present a patient who had epithelial ingrowth to the backside of the flap through a central LASIK flap laceration with a stellate shape. The patient had undergone uncomplicated bilateral LASIK surgery 3 years before the trauma. Because the epithelial ingrowth was suspected during the first visit 2 weeks after trauma, and definite epithelial ingrowth was noted during the additional 2 week observation period, the ingrown epithelial tissue was removed mechanically with a number 15 blade after lifting of the flap 4 weeks after the trauma. An amniotic membrane overlay was applied over the cornea and was sutured tightly to the episclera to firmly press down the flap to the remaining posterior stroma, to prevent growth of the epithelium again to the backside of the flap. At the last follow-up visit, 5 months after surgery, the patient's visual acuity remained stabilized with no sign of recurrent epithelial ingrowth. Conclusion: These results showed that an amniotic membrane patch can be a useful adjuvant in the treatment of epithelial ingrowth, even on the central stellate laceration of the LASIK flap over the visual axis.

We identified the characteristics of myeloid-derived suppressor cells (MDSCs) and investigated their mechanism of induction and their functional role in allograft rejection using a murine corneal allograft model. In mice, MDSCs coexpress CD11b and myeloid differentiation antigen Gr-1. Gr-1+CD11b+ cells infiltrated allografted corneas between 4 d and 4 wk after surgery; however, the frequencies of Gr-1+CD11b+ cells were not different between accepted and rejected allografts or in peripheral blood or BM. Of interest, Gr-1intCD11b+ cells, but not Gr-1hiCD11b+ cells, infiltrated the accepted graft early after surgery and expressed high levels of immunosuppressive cytokines, including IL-10, TGF-β, and TNF-related apoptosis-inducing ligand. This population remained until 4 wk after surgery. In vitro, only high dose (>100 ng/ml) of IFN-γ plus GM-CSF could induce immunosuppressive cytokine expression in Gr-1intCD11b+ cells. Furthermore, adoptive transfer of Gr-1intCD11b+ cells reduced T cell infiltration, which improved graft survival. In conclusion, high-dose IFN-γ in allograft areas is essential for development of Gr-1intCD11b+ MDSCs in corneal allografts, and subtle environmental changes in the early period of the allograft can result in a large difference in graft survival.

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.

PURPOSE. The purpose of this study was to investigate the effectiveness of tumor necrosis factor (TNF)-a blocker for treatment of dry eye (DE)-induced inflammation and determine a more effective method to suppress lacrimal gland inflammation. Efficacy of topical versus systemic administration of TNF-a blockers was determined using a murine dry eye (DE) model. METHODS. The TNF-a blocker HL036 was developed by modification of the TNF receptor I. Protein purity, binding affinity, and clearance of TNF-a was compared with etanercept. Using DE-induced C57BL/6 mice, corneal erosion and goblet cell counts were measured after subcutaneous or topical treatment with etanercept or HL036. Inflammatory cytokines in cornea and lacrimal glands were determined by quantitative RT-PCR and ELISA. RESULTS. HL036 showed TNF-a binding affinity comparable to etanercept, as measured by surface plasmon resonance. HL036 concentration was significantly higher in cornea and anterior segment than etanercept and effectively eliminated TNF-a on ocular surfaces. Etanercept was preferentially concentrated in the posterior segment. Corneal erosion and goblet cell counts were improved only with topically applied etanercept and HL036. Ocular surface IFN-c, IL-6, and IL-21 were significantly decreased by topical HL036. DE-induced lacrimal gland IFN-c and IL-6 expression was effectively suppressed by topical etanercept and HL036. CONCLUSIONS. Topical TNF-a blockers effectively suppressed lacrimal gland and corneal inflammation by suppressing IFN-c, IL-21, and IL-6. Differences in TNF-a affinity, clearance, and local concentration of blockers may account for the anti-inflammatory effects in different ocular regions.

To the Editor: We recently identified a family with lattice corneal dystrophy type IIIA (LCD IIIA) associated with a novel threonine-to-proline (T621P) mutation in the transforming growth factor-beta induced (TGFBI) gene. The 50-year-old female proband (II-2) visited our clinic because of decreased visual acuity. Slit-lamp examination disclosed thick, branching, refractile, ropy lattice lines located in both stromal corneas, which extended to the limbus radially (Figures AA-AC, available in the online version of this article). The right cornea showed a higher number of lattice lines than the left cornea. Molecular analysis involving bidirectional complete sequencing demonstrated a novel T621P mutation in exon 14 of TGFBI. After we identified this new mutation, we performed genetic and clinical examinations on 10 other family members (Severance Hospital Institutional Review Board [No. 4-2014-1046]). The corneas of elderly affected members (I-1, II-1, and II-2) showed the LCD IIIA phenotype with asymmetry between both corneas, as reported for LCD IIIA. Three family members in their mid-twenties (III-1, III2, and III-4) had clear corneas despite having the mutated TGFBI gene (Figure AD). This suggests that the family had a late-onset form of LCD IIIA. The 26-year-old son of the proband (III-3), who had undergone LASIK 5 years earlier at a different facility, maintains clear corneas and showed no mutation in the recent genetic test. He was aware that his grandmother and mother had visual problems but was not aware of the genetic basis of the condition. Therefore, he did not notify the surgeon of any visual problems of the family before the LASIK procedure because he was not asked about them. The relatively late onset of LCD IIIA is favorable for young affected individuals in that visual acuity is well preserved until advanced age. However, the III-3 family member, who is the only one having the normal gene among the four genetically examined cousins, highlights the worrying possibility of young adults harboring the mutation but having clear corneas and undergoing LASIK.

The pathogenesis of immune-mediated lacrimal gland (LG) dysfunction in Sjogren's syndrome has been thoroughly studied. However, the majority of dry eye (DE) is not related to Sjogren type, and its pathophysiology remains unclear. The purpose of this study was to determine and investigate the protective mechanisms against DE stress in mice. DE induced prominent blood vessel loss without apoptosis or necrosis in the LG. Autophagic vacuoles, distressed mitochondria, and stressed endoplasmic reticulum were observed via electron microscopy. Immunoblotting confirmed the increase in autophagic markers. Glycolytic activities were enhanced with increasing levels of succinate and malate that, in turn, activated hypoxia-inducible factor (HIF)-1 alpha. Interestingly, the areas of stable HIF-1 alpha expression overlapped with COX-2 and MMP-9 upregulation in LGs of DE-induced mice. We generated HIF-1 alpha conditional knockout (CKO) mice in which HIF-1 alpha expression was lost in the LG. Surprisingly, normal LG polarities and morphologies were completely lost with DE induction, and tremendous acinar cell apoptosis was observed. Similar to Sjogren's syndrome, CD3(+) and CD11b(+) cells infiltrated HIF-1 alpha CKO LGs. Our results show that DE induced the expression of HIF-1 alpha that activated autophagy signals to prevent further acinar cell damage and to maintain normal LG function.

Comparison of Surface Roughness and Bacterial Adhesion between Cosmetic Contact Lenses and Conventional Contact Lenses 지용우1⋅홍순호2⋅정동룡3⋅김응권1,4⋅이형근1,4 Yong Woo Ji, MD, Soon Ho Hong, Dong Yong Chung, Eung Kweon Kim, MD, Hyung Keun Lee, MD 연세대학교 의과대학 안과학교실 시기능개발 연구소, 연세대학교 의과대학 강남세브란스병원 진단검사의학 미생물학과, 연세 의생명연구원 형태학연구실, 연세대학교 의과대학 안과학교실 각막이상증 연구소 Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea Division of Microbiology, Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea Morphology Lab., Yonsei Biomedical Research Institute, Seoul, Korea Institute of Corneal Dystrophy Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea

Purpose: We analyzed dose distribution depending on the width of gating window to determine the proper width of gating window in gated radiation therapy.Methods: A three dimensional breathing simulator with house phantom was built to simulate periodic sinusoidal breathing motion of 4 seconds/cycle and 3cm fan shape movement. This was driven synchronized with Real‐time Position Management (RPM) system (Varian Medical Systems, Palo Alto, CA, USA), and thereafter 4D‐CT images were acquired. Three treatment fields (0°, 120°, 240°) with gating plan using treatment planning system (Eclipse, Varian, USA) were performed aimed to be exposed 200cGy to isocenter. Dose evaluations regarding static, non‐gated motion, 60% (phase of 20%–80%), 40% (phase of 30%–70%), 30% (phase of 40%–70%), 20% (phase of 40%–60%) and 15% (phase of 40%–55%) of gated motion were carried out using EBT2 film, and extents of field size, high dose exposed, penumbra were analyzed. Results: In most cases, dose differences compared to static were getting decreased as the width of gating window was decreased. Non‐gated motion showed −74.5% dose discrepancies compared to static exposed, whereas 15% respiratory gating window showed within 1% dose difference. Dose differences of 40% gating window was −30.7% whereas 30% gating window showed −6.3% dose discrepancies. Dose difference was rapidly reduced from 30% gating window against non‐gated motion to 40% gating window in all cases of field size, high dose area, and penumbra. Conclusions: 15% respiratory gating window was regarded the most ideal width of gating window, but it will significantly increase beam delivery time over a conventional treatment. Therefore, considering beam delivery time and dose distributions of high dose area, field size, and penumbra, 30% respiratory gating window would be recommended. This work was supported by Nuclear Research & Development Program of the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST).