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1.
  • Adil, Mohammed Yasin, et al. (author)
  • Meibomian Gland Morphology Is a Sensitive Early Indicator of Meibomian Gland Dysfunction
  • 2019
  • In: American Journal of Ophthalmology. - : ELSEVIER SCIENCE INC. - 0002-9394 .- 1879-1891. ; 200, s. 16-25
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To investigate the relationship between meibomian gland (MG) morphology and clinical dry eye tests in patients with meibomian gland dysfunction (MGD). DESIGN: Cross-sectional study. SUBJECTS: Total 538 MGD patients and 21 healthy controls. METHODS: MG loss on meibography images of upper (UL) and lower lids (LL) was graded on a scale of 0 (lowest degree of MG loss) to 3. MG length, thickness, and interglandular space in the UL were measured. Clinical tests included meibum expression and quality, tear film break-up time, ocular staining, osmolarity, Schirmer I, blink interval timing, and Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: Mean UL and LL meibogrades were significantly higher in MGD patients compared to controls (P amp;lt; .001 for UL and LL). The sensitivity and specificity of the meibograde as a diagnostic parameter for MGD was 96.7% and 85%, respectively. Schirmer I was significantly increased in MGD patients with meibograde 1 compared to patients with meibograde 0, 2, and 3 in the UL (P amp;lt; .05 ). MG thickness increased with higher meibograde (P amp;lt; .001). MG morphology correlated significantly but weakly with several clinical parameters (P amp;lt; .05). OSDI did not correlate with any MG morphologic parameter. CONCLUSIONS: Grading of MG loss using meibograde effectively diagnoses MGD. Compensatory mechanisms such as increased aqueous tear production and dilation of MGs make early detection of MGD difficult by standard clinical measures of dry eye, whereas morphologic analysis of MGs reveals an early stage of MGD, and therefore represents a complementary clinical parameter with diagnostic potential. (C) 2018 Elsevier Inc. All rights reserved.
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2.
  • Landsend, Erlend C. S., et al. (author)
  • Characteristics and Utility of Fundus Autofluorescence in Congenital Aniridia Using Scanning Laser Ophthalmoscopy
  • 2019
  • In: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 60:13, s. 4120-4128
  • Journal article (peer-reviewed)abstract
    • PURPOSE. To investigate fundus autofluorescence (FAF) and other fundus manifestations in congenital aniridia. METHODS. Fourteen patients with congenital aniridia and 14 age- and sex-matched healthy controls were examined. FAF images were obtained with an ultra-widefield scanning laser ophthalmoscope. FAF intensity was quantified in the macular fovea and in a macular ring surrounding fovea and related to an internal reference within each image. All aniridia patients underwent an ophthalmologic examination, including optical coherence tomography and slitlamp biomicroscopy. RESULTS. Mean age was 28.4 +/- 15.0 years in both the aniridia and control groups. Fovea could be defined by subjective assessment of FAF images in three aniridia patients (21.4%) and in all controls (P = 0.001). Mean ratio between FAF intensity in the macular ring and fovea was 1.01 +/- 0.15 in aniridia versus 1.18 +/- 0.09 in controls (P = 0.034). In aniridia, presence of foveal hypoplasia evaluated by biomicroscopy correlated with lack of foveal appearance by subjective analyses of FAF images (P = 0.031) and observation of nystagmus (P = 0.009). CONCLUSIONS. Aniridia patients present a lower ratio between FAF intensity in the peripheral and central macula than do healthy individuals. Both subjective and objective analyses of FAF images are useful tools in evaluation of foveal hypoplasia in aniridia.
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3.
  • Landsend, Erlend C. S., et al. (author)
  • The Level of Inflammatory Tear Cytokines is Elevated in Congenital Aniridia and Associated with Meibomian Gland Dysfunction
  • 2018
  • In: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 59:5, s. 2197-2204
  • Journal article (peer-reviewed)abstract
    • PURPOSE. To investigate the tear cytokine profile in congenital aniridia, and correlate cytokine levels with ophthalmologic findings. METHODS. We examined 35 patients with aniridia and 21 healthy controls. Tear fluid was collected with Schirmer I test and capillary tubes from each eye, and the concentration of 27 inflammatory cytokines determined using multiplex bead assay. Eyes of all participants were examined with tests for dry eye disease, including evaluation of meibomian glands (meibography). Differences in cytokine levels between the two groups were analyzed, and correlations between cytokine concentrations and ophthalmologic findings in the aniridia group investigated. RESULTS. The concentrations of six tear cytokines were significantly higher in aniridia patients than controls in both eyes, and included interleukin 1 beta (IL-1 beta), IL-9, IL-17A; eotaxin; basic fibroblast growth factor (bFGF/FGF2); and macrophage inflammatory protein 1 alpha (MIP-1 alpha/ CCL3). The ratio between the anti-inflammatory IL-1RA and the proinflammatory IL-1 beta was significantly lower in patients than controls in both eyes (P = 0.005 right eye and P = 0.001 left eye). Increasing concentration of IL-1 beta, IL-9, IL-17A, FGF2, and MIP-1 alpha correlated with parameters for meibomian gland dysfunction (MGD) in the aniridia group, including increasing atrophy of meibomian glands, and shorter break-up time of the tear film. CONCLUSIONS. A number of pro-inflammatory cytokines are significantly elevated in tear fluid from aniridia patients, and correlate with parameters for MGD in aniridia. Increased inflammation of the ocular surface may be a factor in the development of MGD in aniridia patients, and explain the high prevalence of MGD and dry eye disease in these patients.
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4.
  • Landsend, Erlend S., et al. (author)
  • The genetics of congenital aniridia-a guide for the ophthalmologist
  • 2018
  • In: Survey of ophthalmology. - : ELSEVIER SCIENCE INC. - 0039-6257 .- 1879-3304. ; 63:1, s. 105-113
  • Research review (peer-reviewed)abstract
    • Congenital aniridia is a rare panocular disease caused by fundamental disturbances in the development of the eye, characterized primarily by hypoplasia of the iris and macula. Severe secondary complications such as keratopathy, cataract, and glaucoma are common and often lead to considerable visual impairment or blindness. Many complications in aniridia patients are difficult to treat and present a challenge for the ophthalmologist. Increasingly, associated nonocular features of the disease are also being recognized. Over the past decades, major steps have been made in the understanding of the genetic basis of aniridia. Moreover, recent studies have prepared the ground for future treatment options based on specific mutations. Therefore, specific knowledge about genetics in aniridia has become more important than ever. We provide an overview of the field of aniridia genetics and its clinical implications. (C) 2017 Elsevier Inc. All rights reserved.
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5.
  • Magno, Morten Schjerven, et al. (author)
  • Chambered warm moist air eyelid warming devices - a review
  • 2022
  • In: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 100:5, s. 499-510
  • Research review (peer-reviewed)abstract
    • Background Eyelid warming is an important treatment for meibomian gland dysfunction (MGD). Specialized chambered devices, using warm moist air have been developed. Purpose To critically evaluate the literature on the safety and efficacy of chambered warm moist air devices in MGD treatment and pinpoint areas of future research. Methods PubMed and Embase were searched on 06 June 2021. The search term was (warm OR heat OR steam OR goggle OR spectacle OR moist air) AND (meibomian OR MGD OR blepharitis OR eyelid OR dry eye OR DED). All relevant articles with available English full text were included. Results Eighteen articles assessing the application of chambered warm moist air eyelid warming devices were identified. In single-application studies, steam-based eyelid warming increased the eyelid temperature and improved symptoms, lipid layer thickness, and tear film breakup time (TBUT). In treatment studies, the steam-based devices improved TBUT and symptom scores. However, in the only randomized controlled trial (RCT) comparing chambered steam-based heat to hot towel treatment, there was no difference between groups for the primary outcome measure; the proportion of subjects noting symptom improvement after 4 weeks. Conclusion Currently available chambered warm moist air eyelid warming devices are safe and effective at raising eyelid temperature to therapeutic levels and improving signs and symptoms of dry eye. However, it is not clear if they provide a greater benefit than other eyelid warming therapies. Further well-conducted RCTs comparing moist and dry heat devices should be conducted on patients across the range of DED severities and subtype spectrum.
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6.
  • Magno, Morten Schjerven, et al. (author)
  • Hot towels: The bedrock of Meibomian gland dysfunction treatment-A review
  • 2023
  • In: Contact lens & anterior eye. - : ELSEVIER. - 1367-0484 .- 1476-5411. ; 46:2
  • Research review (peer-reviewed)abstract
    • Background: Meibomian gland dysfunction (MGD) reduces quality-of-life and hinders work productivity of millions of patients, with high direct and indirect societal costs. Thickened meibum obstructs the glands and disrupts ocular surface health. Heating the eyelids to soften and express meibum from the glands can be beneficial. The most accessible method for eyelid warming uses heated, wet towels. However, the efficacy of this treatment is reliant on the methodology, and evidence-based best-practice recommendations are needed. Purpose: To evaluate the literature on hot towels in MGD treatment and recommend a best-practice protocol for future research and patient treatment.Methods: Studies were identified through PubMed on the May 28, 2021, with the search terms: (warm* OR heat* OR thermal* OR towel OR wet towel) AND (meibomian OR MGD OR eyelid OR "dry eye" OR DED). All relevant original articles with English full-text were included.Results: The search yielded 903 results, of which 22 met the inclusion criteria. Across studies, hot towels were found to be effective at reducing ocular symptoms. However, without reheating, the temperature quickly fell below the therapeutic range, which was deemed to be between 40 degrees C and 47 degrees C. Towels heated to around 45 degrees C and reheated every-two minutes were most effective at increasing eyelid temperature, comparable or better than several commercially available eyelid warming devices. No adverse effects were reported in the studies. Conclusion: Hot towel treatment effectively warms the eyelids and reduces ocular symptoms, but must be standardized, and towels reheated to achieve maximum benefit. Future research should assess patient satisfaction with different hot towel treatment methods that reheat or replace the towel at least every-two minutes, to establish which methods yield the greatest compliance. Guidelines or clinical recommendations that do not mention the need for regular reheating during hot towel compress treatment should be updated to include this.
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7.
  • Olafsson, Jonatan, et al. (author)
  • TheraPearl Eye Mask and Blephasteam for the treatment of meibomian gland dysfunction : a randomized, comparative clinical trial
  • 2021
  • In: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Meibomian gland dysfunction (MGD) is the most common cause of dry eye disease (DED). In this study, we aimed to compare the effects of eyelid warming treatment using either TheraPearl Eye Mask (Bausch & Lomb Inc., New York, USA) or Blephasteam (Spectrum Thea Pharmaceuticals LTD, Macclesfield, UK) in a Norwegian population with mild to moderate MGD-related DED. An open label, randomized comparative trial with seventy patients (49 females, 21 males; mean age 53.6 years). Patients were randomly assigned to treatment with Blephasteam (n = 37) or TheraPearl (n = 33). All received a hyaluronic acid based artificial tear substitute (Hylo-Comod, Ursapharm, Saarbrucken, Germany). Patients were examined at baseline, and at three and six months initiation of treatment. Treatment efficacy was primarily evaluated by fluorescein breakup time (FBUT) and Ocular Surface Disease Index (OSDI) scores. Other outcome measures included ocular surface staining (OSS), Schirmers test, and meibomian quality and expressibility. Baseline parameter values did not differ between the groups. After six months of treatment, Blephasteam improved FBUT by 3.9 s (p < 0.01) and OSDI by 13.7 (p < 0.01), TheraPearl improved FBUT by 2.6 s (p < 0.01) and OSDI by 12.6 (p < 0.01). No difference between treatments was detected at 6 months (p = 0.11 for FBUT and p = 0.71 for OSDI), nor were there differences in the other tested parameters between the treatment groups. Blephasteam and TheraPearl are equally effective in treating mild to moderate MGD in a Norwegian population after 6-months of treatment. Clinicaltrials.gov ID: NCT03318874; Protocol ID: 2014/1983; First registration: 24/10/2017.
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8.
  • Xiao, Jiaxin, et al. (author)
  • Diagnostic Test Efficacy of Meibomian Gland Morphology and Function
  • 2019
  • In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
  • Journal article (peer-reviewed)abstract
    • Meibomian gland dysfunction (MGD) is the leading cause of dry eye and proposed treatments are based on disease severity. Our purpose was to establish reliable morphologic measurements of meibomian glands for evaluating MGD severity. This retrospective, cross-sectional study included 100 MGD patients and 20 controls. The patients were classified into dry eye severity level (DESL) 1-4 based on symptoms and clinical parameters including tear-film breakup time, ocular staining and Schirmer I. The gland loss, length, thickness, density and distortion were analyzed. We compared the morphology between patients and controls; examined their correlations to meibum expressibility, quality, and DESL. Relative to controls, the gland thickness, density and distortion were elevated in patients (p amp;lt; 0.001 for all tests). The area under the receiver operating characteristic curve was 0.98 (95% confidence interval [CI], 0.96-1.0) for gland loss, and 0.96 (CI 0.91-1.0) for gland distortion, with a cutoff value of six distorted glands yielding a sensitivity of 93% and specificity of 97% for MGD diagnosis. The gland distortion was negatively correlated to the meibum expressibility (r = -0.53; p amp;lt; 0.001) and DESL (r = -0.22, p = 0.018). In conclusion, evaluation of meibomian gland loss and distortion are valuable complementary clinical parameters to assess MGD status.
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9.
  • Xiao, Jiaxin, et al. (author)
  • Functional and Morphological Evaluation of Meibomian Glands in the Assessment of Meibomian Gland Dysfunction Subtype and Severity
  • 2020
  • In: American Journal of Ophthalmology. - : ELSEVIER SCIENCE INC. - 0002-9394 .- 1879-1891. ; 209, s. 160-167
  • Journal article (peer-reviewed)abstract
    • PURPOSE: To classify subtypes of meibomian gland dysfunction (MGD) and evaluate the dependency of dry eye signs, symptoms, and parameters on MGD subtype. DESIGN: Cross-sectional study. Study Population: the right eyes of 447 patients with MGD of various subtypes and 20 healthy volunteers. METHODS: Patients were divided into 4 subtypes of MGD based on meibum expression, meibum quality, and MG loss on meibography images (meibograde of 0-6). Subtypes were patients with high meibum delivery (hypersecretory and nonobvious MGD) and those with low meibum delivery (hyposecretory and obstructive MGD). Additional clinical tests included tear film break-up time (TFBUT), ocular staining, osmolarity, Schirmer I, blink interval timing and the Ocular Surface Disease Index (OSDI) questionnaire. RESULTS: A total of 78 eyes had hypersecretory MGD; 49 eyes had nonobvious MGD; 66 eyes had hyposecretory MGD; and 254 eyes had obstructive MGD. Increased tear film osmolarity and lower TFBUT were found in the low-delivery groups; hyposecretory (P = 0.006, P = 0.016) and obstructive MGD (P = 0.008, P = 0.006) relative to high-delivery MGD (hypersecretory and nonobvious groups, respectively). Worse ocular symptoms and ocular staining were also found in low-delivery MGD groups than the high delivery MGD groups (P amp;lt; 0.01 and P amp;lt; 0.006, respectively). " CONCLUSIONS: Patients with low-delivery MGD had worse dry eye parameters and ocular symptoms than those with high meibum delivery, indicating the pivotal role of meibum secretion in ocular surface health that should be targeted in MGD therapy. Furthermore, nonobvious MGD cannot be diagnosed using conventional dry eye tests and requires morphologic assessment of meibography images to confirm MG loss. ((C) 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)
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10.
  • Yazdani, Mazyar, et al. (author)
  • Tear Production Levels and Dry Eye Disease Severity in a Large Norwegian Cohort
  • 2018
  • In: Current Eye Research. - : TAYLOR & FRANCIS INC. - 0271-3683 .- 1460-2202. ; 43:12, s. 1465-1470
  • Journal article (peer-reviewed)abstract
    • Purpose: To determine if the Schirmer I test (without anesthesia) cut-off value is a predictor of dry eye severity in a large Norwegian cohort of dry eye disease (DED) patients, which are grouped into six levels of tear production. Methods: Patients (n = 1090) with DED of different etiologies received an extensive dry eye work-up: osmolarity (Osm), tear meniscus height (TMH), tear film break-up time (TFBUT), ocular protection index (OPI), ocular surface staining (OSS), Schirmer I test (ST), meibum expressibility (ME), and meibum quality (MQ). Classification of dry eye severity level (DESL) and diagnosis of meibomian gland dysfunction (MGD) were also included. The cohort was divided into six groups: below and above cut-off values of 5 (groups 1 and 2), 10 (groups 3 and 4), and 15 mm (groups 5 and 6) of ST. Mann-Whitney test and Chi-Square test were used for group comparison of parameters (p amp;lt;= 0.05). Results: The groups 1, 3, and 5 had values indicating more severe DED than the groups 2, 4, 6 with significant difference in DESL, Osm, TFBUT, OPI, OSS, and TMH. Regardless of the choice of cut-off values, there was no statistically significant difference in ME, MQ, and MGD between groups below and above selected cut-off value. When gender difference was considered in each group, significant difference was only observed for DESL (groups 2, 4, and 5), TFBUT (groups 2, 4, and 5), OPI (groups 2 and 6), and ME (group1). Conclusions: Schirmer I is a robust discriminator for DESL, Osm, TFBUT, OPI, OSS, and TMH, but not for ME, MQ, and MGD. Patients with lower tear production levels presented with more severe DED at all three defined cut-off values. Interestingly, the differences in the mean values of DESL were minimal although statistically significant. Thus, the clinical value of different Schirmer levels appears to be limited.
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11.
  • Bakken, Ingvild M., et al. (author)
  • The use of in vivo confocal microscopy in fungal keratitis - Progress and challenges
  • 2022
  • In: Ocular Surface. - : Elsevier. - 1542-0124. ; 24, s. 103-118
  • Journal article (peer-reviewed)abstract
    • Fungal keratitis (FK) is a serious and sight-threatening corneal infection with global reach. The need for prompt diagnosis is paramount, as a delay in initiation of treatment could lead to irreversible vision loss. Current "gold standard" diagnostic methods, namely corneal smear and culture, have limitations due to diagnostic insensitivity and their time-consuming nature. PCR is a newer, complementary method used in the diagnosis of fungal keratitis, whose results are also sample-dependent. In vivo confocal microscopy (IVCM) is a promising complementary diagnostic method of increasing importance as it allows non-invasive real-time direct visualization of potential fungal pathogens and manifesting infection directly in the patients cornea. In numerous articles and case reports, FK diagnosis by IVCM has been evaluated, and different features, approaches, sensitivity/specificity, and limitations have been noted. Here, we provide an up-to-date, comprehensive review of the current literature and present the authors combined recommendations for fungal identification in IVCM images, while also looking to the future of FK assessment by IVCM using artificial intelligence methods.
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12.
  • Björkblom, Benny, et al. (author)
  • Xenobiotic- and Serum-Free Culture of Oral Mucosal Epithelial Cells on Contact Lenses
  • 2016
  • In: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 41:1, s. 20-27
  • Journal article (peer-reviewed)abstract
    • Purpose/aim: Cultured autologous oral mucosal epithelial cells (OMECs) have proven useful in the treatment of ocular surface disorders. This study is the first to investigate the potential of expanding OMEC in a xenobiotic- and serum-free medium using therapeutic contact lenses (CLs) as a substrate and carrier.Materials and methods: Porcine OMEC were seeded on laminin-coated lotrafilcon A therapeutic CLs with the density of 8x10(4)cells/lens and cultured in a defined serum and xenobiotic-free medium. Confocal immunofluorescence microscopy was used to analyze the following: (1) cellular morphology by using rhodamine-phalloidin staining of F-actin, (2) phenotype by applying antibodies against the progenitor cell marker p63 and the putative stem cell marker ABCG2 and (3) cell viability by using propidium iodide and Hoechst 33342 dual staining.Results: Porcine OMEC attached well to the CLs, and cell-to-cell contacts were evident. After three days in culture, the OMEC displayed a confluent monolayer with uniform cobblestone morphology, whereas stratified cultures with 2-3 layers were formed after six days. No significant difference in expression of p63 was observed after three-day culture (79.414.8%) compared with six-day culture (60.3 +/- 18.9%). ABCG2 expression in the basal cell layer was 6.3 +/- 1.0% and 4.8 +/- 1.8% after three- and six-day culture, respectively. The basal layer viability of cultured OMECs was 99.3 +/- 0.2% and 82.8 +/- 1.1% after three and six days culture, respectively.Conclusions: The use of therapeutic CLs has potential as a substrate and carrier for OMEC cultured in a xenobiotic- and serum-free culture system.
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14.
  • Fineide, Fredrik, et al. (author)
  • Topical glaucoma medications - Clinical implications for the ocular surface
  • 2022
  • In: Ocular Surface. - : Elsevier. - 1542-0124. ; 26, s. 19-49
  • Journal article (peer-reviewed)abstract
    • Glaucoma is a leading cause of irreversible blindness. The use of topical eye drops to reduce intraocular pressure remains the mainstay treatment. These eye drops frequently contain preservatives designed to ensure sterility of the compound. A growing number of clinical and experimental studies report the detrimental effects of not only these preservatives but also the active pharmaceutical compounds on the ocular surface, with resultant tear film instability and dry eye disease. Herein, we critically appraise the published literature exploring the effects of preservatives and pharmaceutical compounds on the ocular surface.
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15.
  • Fostad, Ida G., et al. (author)
  • Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility
  • 2016
  • In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 11:5, s. e0155214-
  • Journal article (peer-reviewed)abstract
    • The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sjogrens syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52% women and 48% men) with DED were included. Patient demographics were: 0 to 19 years (1%), 20 to 39 (25%), 40 to 59 (34%), 60 to 79 (35%) and 80 to 99 (5%). Xerostomia, defined as "daily symptoms of dry mouth the last three months" (as presented in SSQ) was reported by 23% of the patients. Female sex was more common among patients with xerostomia (81%) than among non-xerostomia patients (44%; Pamp;lt; 0.001). Patients with xerostomia (60 +/- 15 years) were older than those without xerostomia (51 +/- 17; Pamp;lt; 0.001). The use of prescription drugs was more prevalent among xerostomia patients (65%) than among non-xerostomia patients (35%; Pamp;lt; 0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 +/- 10.0) than those without xerostomia (12.9 +/- 8.0; Pamp;lt; 0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 +/- 0.7) than those without xerostomia (0.7 +/- 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients.
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16.
  • Fostad, Ida G., et al. (author)
  • Identification of Objective Morphometric Markers of Xerostomia in the Oral Mucosa Epithelium with In Vivo Confocal Microscopy
  • 2017
  • In: Microscopy and Microanalysis. - : CAMBRIDGE UNIV PRESS. - 1431-9276 .- 1435-8115. ; 23:1, s. 88-96
  • Journal article (peer-reviewed)abstract
    • The purpose of this work was to determine whether the morphology of the oral mucosa epithelium (OME) of patients with xerostomia differ from patients without xerostomia. In total, 34 patients with dry eye disease (DED) with or without xerostomia were examined at The Norwegian Dry Eye Disease Clinic with in vivo confocal microscopy of the lower lip. In addition, age- and gender-matched healthy controls (HC) were included. DED patients with xerostomia had a higher superficial to deep backscatter ratio compared with DED patients without xerostomia (p=0.002) and HC (p=0.001). Regression analysis demonstrated that this ratio was related to xerostomia independently of gender and age (pamp;lt;0.001). Sensitivity and specificity of detecting xerostomia were 0.78 and 0.85, respectively, when using a superficial to deep backscatter ratio cut-off value of 0.995 (p=0.004). The mean nucleus to cytosol backscatter ratio in the superficial OME was lower in patients with xerostomia than in those without xerostomia (p=0.034). In vivo confocal microscopy is a potential tool for evaluating the oral cavity and to assess changes in the OME associated with xerostomia, objectively and quantitatively. The cause of the increased backscatter in the superficial OME in xerostomia, however, remains to be elucidated.
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17.
  • He, Min, et al. (author)
  • Artificial Polymeric Scaffolds as Extracellular Matrix Substitutes for Autologous Conjunctival Goblet Cell Expansion
  • 2016
  • In: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 57:14, s. 6134-6146
  • Journal article (peer-reviewed)abstract
    • PURPOSE. We fabricated and investigated polymeric scaffolds that can substitute for the conjunctival extracellular matrix to provide a substrate for autologous expansion of human conjunctival goblet cells in culture. METHODS. We fabricated two hydrogels and two silk films: (1) recombinant human collagen (RHC) hydrogel, (2) recombinant human collagen 2-methacryloylxyethyl phosphorylcholine (RHC-MPC) hydrogel, (3) arginine-glycine-aspartic acid (RGD) modified silk, and (4) poly-D-lysine (PDL) coated silk, and four electrospun scaffolds: (1) collagen, (2) poly(acrylic acid) (PAA), (3) poly(caprolactone) (PCL), and (4) poly(vinyl alcohol) (PVA). Coverslips and polyethylene terephthalate (PET) were used for comparison. Human conjunctival explants were cultured on scaffolds for 9 to 15 days. Cell viability, outgrowth area, and the percentage of cells expressing markers for stratified squamous epithelial cells (cytokeratin 4) and goblet cells (cytokeratin 7) were determined. RESULTS. Most of cells grown on all scaffolds were viable except for PCL in which only 3.6 +/- 2.2% of the cells were viable. No cells attached to PVA scaffold. The outgrowth was greatest on PDL-silk and PET. Outgrowth was smallest on PCL. All cells were CK7-positive on RHCMPC while 84.7 +/- 6.9% of cells expressed CK7 on PDL-silk. For PCL, 87.10 +/- 3.17% of cells were CK7-positive compared to PET where 67.10 +/- 12.08% of cells were CK7-positive cells. CONCLUSIONS. Biopolymer substrates in the form of hydrogels and silk films provided for better adherence, proliferation, and differentiation than the electrospun scaffolds and could be used for conjunctival goblet cell expansion for eventual transplantation once undifferentiated and stratified squamous cells are included. Useful polymer scaffold design characteristics have emerged from this study.
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18.
  • Islam, Rakibul, et al. (author)
  • Effect of Storage Temperature on Structure and Function of Cultured Human Oral Keratinocytes
  • 2015
  • In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 10:6, s. e0128306-
  • Journal article (peer-reviewed)abstract
    • Purpose/Aims To assess the effect of storage temperature on the viability, phenotype, metabolism, and morphology of cultured human oral keratinocytes (HOK). Materials and Methods Cultured HOK cells were stored in HEPES- and sodium bicarbonate-buffered Minimum Essential Medium (MEM) at nine temperatures in approximately 4 degrees C increments from 4 degrees C to 37 degrees C for seven days. Cells were characterized for viability by calcein fluorescence, phenotype retention by immunocytochemistry, metabolic parameters (pH, glucose, lactate, and O-2) within the storage medium by blood gas analysis, and morphology by scanning electron microscopy and light microscopy. Results Relative to the cultured, but non-stored control cells, a high percentage of viable cells were retained only in the 12 degrees C and 16 degrees C storage groups (85%+/- 13% and 68%+/- 10%, respectively). Expression of ABCG2, Bmi1, C/EBP delta, PCNA, cytokeratin 18, and caspase-3 were preserved after storage in the 5 groups between 4 degrees C and 20 degrees C, compared to the non-stored control. Glucose, pH and pO(2) in the storage medium declined, whereas lactate increased with increasing storage temperature. Morphology was best preserved following storage of the three groups between 12 degrees C, 16 degrees C, and 20 degrees C. Conclusion We conclude that storage temperatures of 12 degrees C and 16 degrees C were optimal for maintenance of cell viability, phenotype, and morphology of cultured HOK. The storage method described in the present study may be applicable for other cell types and tissues; thus its significance may extend beyond HOK and the field of ophthalmology.
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19.
  • Jackson, Catherine, et al. (author)
  • Effect of Storage Temperature on Cultured Epidermal Cell Sheets Stored in Xenobiotic-Free Medium
  • 2014
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e105808-
  • Journal article (peer-reviewed)abstract
    • Cultured epidermal cell sheets (CECS) are used in regenerative medicine in patients with burns, and have potential to treat limbal stem cell deficiency (LSCD), as demonstrated in animal models. Despite widespread use, short-term storage options for CECS are limited. Advantages of storage include: flexibility in scheduling surgery, reserve sheets for repeat operations, more opportunity for quality control, and improved transportation to allow wider distribution. Studies on storage of CECS have thus far focused on cryopreservation, whereas refrigeration is a convenient method commonly used for whole skin graft storage in burns clinics. It has been shown that preservation of viable cells using these methods is variable. This study evaluated the effect of different temperatures spanning 4 degrees C to 37 degrees C, on the cell viability, morphology, proliferation and metabolic status of CECS stored over a two week period in a xenobiotic-free system. Compared to non-stored control, best cell viability was obtained at 24 degrees C (95.2 +/- 9.9%); reduced cell viability, at approximately 60%, was demonstrated at several of the temperatures (12 degrees C, 28 degrees C, 32 degrees C and 37 degrees C). Metabolic activity was significantly higher between 24 degrees C and 37 degrees C, where glucose, lactate, lactate/glucose ratios, and oxygen tension indicated increased activation of the glycolytic pathway under aerobic conditions. Preservation of morphology as shown by phase contrast and scanning electron micrographs was best at 12 degrees C and 16 degrees C. PCNA immunocytochemistry indicated that only 12 degrees C and 20 degrees C allowed maintenance of proliferative function at a similar level to non-stored control. In conclusion, results indicate that 12 degrees C and 24 degrees C merit further investigation as the prospective optimum temperature for short-term storage of cultured epidermal cell sheets.
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20.
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21.
  • Landsend, Erlend C. S., et al. (author)
  • Congenital aniridia - A comprehensive review of clinical features and therapeutic approaches
  • 2021
  • In: Survey of ophthalmology. - : Elsevier Science INC. - 0039-6257 .- 1879-3304. ; 66:6, s. 1031-1050
  • Research review (peer-reviewed)abstract
    • Congenital aniridia is a rare genetic eye disorder with total or partial absence of the iris from birth. In most cases the genetic origin of aniridia is a mutation in the PAX6 gene, lead-ing to involvement of most eye structures. Hypoplasia of the fovea is usually present and is associated with reduced visual acuity and nystagmus. Aniridia-associated keratopathy, glaucoma, and cataract are serious and progressive complications that can further reduce visual function. Treatment of the ocular complications of aniridia is challenging and has a high risk of side effects. New approaches such as stem cell therapy may, however, offer better prognoses. We describe the various ocular manifestations of aniridia, with a special focus on conditions that commonly require treatment. We also review the growing literature reporting systemic manifestations of the disease. (c) 2021 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ).
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22.
  • Van Velthoven, Arianne J. H., et al. (author)
  • Future directions in managing aniridia-associated keratopathy
  • 2023
  • In: Survey of ophthalmology. - : ELSEVIER SCIENCE INC. - 0039-6257 .- 1879-3304. ; 68:5, s. 940-956
  • Research review (peer-reviewed)abstract
    • Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.
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