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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.

Many recent studies have demonstrated the efficacy of intense pulsed light (IPL) for the treatment of meibomian gland dysfunction (MGD); however, its effective treatment targets have not yet been elucidated. This study aimed to investigate the baseline characteristics associated with an improvement in symptoms after IPL treatment; to examine the course of change in inflammatory tear cytokines, meibomian gland function, and tear stability; and to investigate the correlation between cytokines and ocular surface parameters. Thirty participants underwent three sessions of IPL treatment. During each examination, tear film lipid layer interferometry, meibography, tear meniscus height measurement, tear sampling, and slit-lamp examination were performed, and the Ocular Surface Disease Index (OSDI) questionnaire was administered. Meibum quality, meibum expressibility, lid margin abnormality, tear film break-up time (TBUT), ocular surface staining, and the OSDI significantly improved after treatment. Poor meibum expressibility and short TBUT were associated with greater recovery in the OSDI after IPL. Tear levels of IL-4, IL-6, IL-10, IL-17A, and TNF-α decreased after IPL, and IL-6, and TNF-α were correlated with the improvement in meibum expressibility. Therefore, IPL treatment improved meibomian gland function, stabilized the tear film, and decreased ocular surface inflammation. Patients with obstructive MGD and tear instability were more likely to experience an improvement in ocular discomfort after IPL treatment.

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.

We aimed to determine the clinical impact of conjunctivochalasis (CCh) and its correction using high-frequency radiowave electrosurgery (HFR-ES), for signs and symptoms of dry eye disease (DED). Forty patients diagnosed with symptomatic CCh were prospectively enrolled. As a result, patients with CCh had moderate to severe DED and most of them exhibited meibomian gland dysfunction (MGD). Corneo-conjunctival fluorescein staining score (CFS) and all lid-parallel-conjunctival-folds scores (LIPCOFs) were positively correlated. Nasal LIPCOF significantly correlated with symptoms and tear volume. Central, temporal, and total LIPCOF significantly correlated with MG loss, MGD stage, and lipid layer thickness. Independent significant factors associated with total LIPCOF included CFS, tear break-up time, and MGD stage. One month following HFR-ES, CCh was completely resolved in all cases. Patient age and preoperative nasal LIPCOF were determinants of outcomes associated with postoperative improvements in symptoms. Ocular surface parameters significantly improved, but MGD-related signs did not. Collectively, CCh associated with MGD severity deteriorates not only tear film stability and reservoir capacity, leading to DED exacerbation. Therefore, CCh should be corrected in patients with DED and MGD. Younger patients with nasal CCh are likely to experience more symptomatic relief after HFR-ES. Particularly, management for MGD should be maintained after CCh correction.

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.

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.

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

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.

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.

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).