Ocular surface and tear functions after topical cyclosporine treatment in dry eye patients with chronic graft-versus-host disease.

PubMed

Wang, Y; Ogawa, Y; Dogru, M; Kawai, M; Tatematsu, Y; Uchino, M; Okada, N; Igarashi, A; Kujira, A; Fujishima, H; Okamoto, S; Shimazaki, J; Tsubota, K

2008-02-01

We investigated the effect of 0.05% topical cyclosporine (Cys) on the ocular surface and tear functions in dry eye patients with chronic GVHD (cGVHD) in a prospective comparative study. Thirty eyes of 15 patients refractory to baseline treatment were recruited and the patients assigned for topical Cys treatment group (14 eyes of 7 patients) and control group (12 eyes of 6 patients) respectively. Two patients dropped out because of intolerable irritation while using topical Cys eye drops. Visual analog scale symptom scores, corneal sensitivity, Schirmer I test value, tear film break-up time (TBUT), tear evaporation rate and ocular surface vital staining scores were recorded at baseline and at the end of the following one month. Conjunctival impression and brush cytology were performed before and after the treatment. After topical Cys treatment, significant improvements were found in symptom scores, corneal sensitivity, tear evaporation rate, TBUT, vital staining scores, goblet cells density, conjunctival squamous metaplasia grade, inflammatory cell numbers and the MUC5AC expression. Our study suggests that 0.05% topical Cys may be an effective treatment for dry eye patients with cGVHD. The improvements in the ocular surface and tear functions resulted presumably from the decreased inflammation, increased goblet cell density and MUC5AC mRNA expression. Bone Marrow Transplantation (2008) 41, 293-302; doi:10.1038/sj.bmt.1705900; published online 5 November 2007.

Scleral patch grafts in the management of uveal and ocular surface tumors.

PubMed

Barman, Manabjyoti; Finger, Paul T; Milman, Tatyana

2012-12-01

To evaluate the outcome of scleral patch grafts in a series of patients undergoing management for uveal and ocular surface tumors. Case series. Ten patients underwent scleral patch grafting. Five patients had uveal melanoma with extrascleral extension, 2 patients had scleromalacia secondary to plaque radiotherapy for uveal melanoma, 2 patients had suspicious uveoscleral nevi, and 1 patient had invasive conjunctival squamous cell carcinoma with scleral necrosis. Retrospective, interventional, noncomparative chart review of patients undergoing treatment for ocular tumors followed by scleral grafts in a tertiary eye care center in the United States between September 2003 and January 2011. Sclera was reconstructed with allogenic scleral grafts. Clinical observations were performed after grafting. Structural integrity, appearance, and stability of the grafts. Ten patients were reviewed. All melanoma cases received plaque radiotherapy with palladium 103. The cases with nevi and squamous cell carcinoma underwent local resection with cryotherapy as primary treatment. In 8 cases, scleral grafting was performed as part of the initial surgery. In all of these cases, satisfactory anatomic and functional outcomes were achieved. In 2 cases with scleromalacia secondary to radiotherapy for uveal melanoma, grafts were placed several years after the initial treatment. In these 2 cases, one showed signs of graft retraction, whereas another showed graft thinning. No patients experienced graft infection, rejection, or tumor recurrence. In this series, scleral grafts were well accepted when placed as part of the primary tumor management despite synchronous radiotherapy, scleral resection, or cryotherapy. Grafting was less successful when performed as a late procedure for radiation-induced scleromalacia. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Ocular surface changes in limbal stem cell deficiency caused by chemical injury: a histologic study of excised pannus from recipients of cultured corneal epithelium.

PubMed

Fatima, A; Iftekhar, G; Sangwan, V S; Vemuganti, G K

2008-09-01

To report histopathologic changes of the ocular surface pannus in patients with severe limbal stem cell deficiency (LSCD). Corneal and conjunctival pannus tissues from 29 patients undergoing ocular reconstruction with cultured limbal cell transplantation were included. The medical records of these patients were reviewed for demographics, aetiologic diagnosis, type of injury, interval between the initial insult and excision of pannus, and medical history involving human amniotic membrane (HAM) or limbal transplantation. The paraffin-embedded tissues were reviewed for epithelial changes, type-degree of fibrosis, degenerative changes, vascular changes, conjunctivalization of corneal surface, and evidence of residual HAM. We attempted a clinicopathologic correlation to understand the pathogenesis of pannus formation in LSCD. The 29 tissues were from 29 eyes of patients with primary aetiology of chemical burn in 89.6% (undetermined in 10.4%) of cases. The pannus showed epithelial hyperplasia in 62%, active fibrosis in 66%, severe inflammation in 21%, giant cell reaction in 28%, and stromal calcification in 14% cases. Goblet cells were seen over the cornea in 64% cases; their absence was associated with squamous metaplasia of the conjunctiva and with long duration of insult. Evidence of residual HAM was noted in 42% cases. The commonest cause of severe LSCD is alkali-induced injury. Goblet cells over the cornea were seen in 60% of cases. HAM used for ocular surface reconstruction could persist for long periods within the corneal pannus, thus raising the need for further studies with long-term follow-up.

An impression cytology based study of ocular surface in an urban population.

PubMed

Mukhopadhyay, Somnath; Dutta, Jayanta; Mitra, Jayati; Prakash, Ratnesh; Datta, Himadri

2013-04-01

To assess the health of ocular surface in a defined urban population, conjunctival goblet cell density and degree of surface squamous metaplasia were utilized as study tools. Two thousand names of those aged between 20 and 79 years from the 2006 electoral register in ward number 63 of Kolkata Corporation area were initially selected. Normal healthy human volunteers without any history of ocular surface disorder were recruited and divided into five age-groups. Impression cytology samples were obtained from interpalpebral part of bulbar conjunctiva from all the participants fixated and stained by a single observer. A stratified, clustered, disproportionate, random sampling method was used. The software used in the statistical analysis was EPI Info. The tests applied were t test and ANOVA. A variation in the number of goblet cells according to gender (women having less cells) and age (20-30 years group having the highest number of cells) was found. Those working outdoors were found to have fewer goblet cells compared to those who stay indoors. The majority of the people had grade 1 cytological appearance in both males and females. There was no statistically significant difference in Nelson's grading with age. People using coal and kerosene to cook were found to have a smaller goblet cell density than those who cooked on LPG or those who did not cook at all. Besides age and sex, environmental factors like the method of cooking and occupational variables (like outdoor activity, prolonged period of computer use, etc.) modify the health of the ocular surface. The results of this study will help put these findings into perspective as public health problems.

[Conjunctival squamous cell carcinoma: paradoxical response to interferon eyedrops].

PubMed

Mata, E; Conesa, E; Castro, M; Martínez, L; de Pablo, C; González, M L

2014-07-01

A 67 year-old male seen for a longstanding corneal-conjunctival tumor. topical interferon α2b (IFN-α2b) 10 U/ml. A significant increase in lesion size was observed after 8 weeks. A surgical excision with cryotherapy was then performed. Pathological examination confirmed the diagnosis of squamous cell carcinoma. At this time the patient was found to have a positive HIV serology. Conjunctival intraepithelial neoplasia (CIN) is a pre-cancerous lesion of the ocular surface. Medical treatment of CIN is essentially with IFN-α2b due to its antiviral/antitumor properties. In patients with HIV, treatment response could be paradoxical. We recommend serology for HIV before treatment with topical IFN-α2b. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Effect of Omega-3 Fatty Acids Dietary Supplementation on Ocular Surface and Tear Film in Diabetic Patients with Dry Eye.

PubMed

Georgakopoulos, Constantine D; Makri, Olga E; Pagoulatos, Dionisios; Vasilakis, Panagiotis; Peristeropoulou, Politimi; Kouli, Vasiliki; Eliopoulou, Maria I; Psachoulia, Caterina

2017-01-01

The objective of this study was to investigate the effect of dietary supplementation with omega-3 fatty acids on ocular surface and tear film in patients with type 2 diabetes suffering from dry eye. Thirty-six patients suffering from type 2 diabetes and moderate to severe dry eye syndrome were included in the study. Patients were assigned to receive omega-3 long-chain polyunsaturated fatty acids for 3 months. Tear film break-up time test, Schirmer-I test, and conjunctival impression cytology analysis were performed on all patients at baseline and after 1 and 3 months. The subjective symptoms of dry eye were evaluated with the Ocular Surface Disease Index (OSDI) questionnaire at the same time points. Patients' average age was 65.57 ± 4.27 years and the mean duration of diabetes was 14.85 ± 5.4 years. There was a statistically significant increase in Schirmer-I test results and tear break-up time score after 3 months of supplementary intake of omega-3 fatty acids compared to baseline (p < 0.05 and p < 0.001, respectively). Impression cytology demonstrated a significantly lower grade of conjunctival squamous cell metaplasia after 1 and 3 months of omega-3 fatty acids intake compared to baseline (p < 0.05 and p < 0.01, respectively). The OSDI score was statistically significant lower both at 1 and 3 months after omega-3 fatty acids supplementation compared to baseline (p < 0.001). Omega-3 fatty acids may effectively improve tear film characteristics, reverse ocular surface features, and alleviate the subjective symptoms associated with dry eye syndrome in patients with type 2 diabetes.

Combined excision, cryotherapy, and intraoperative mitomycin C (EXCRIM) for localized intraepithelial and squamous cell carcinoma of the conjunctiva.

PubMed

Sarici, Ahmet M; Arvas, Sema; Pazarli, Halit

2013-09-01

To report the results of patients undergoing combined excision, cryotherapy, and intraoperative mitomycin-C (EXCRIM) for primary ocular surface squamous neoplasia (OSSN) METHODS: A retrospective review of a non-comparative interventional case series. Histopathologically confirmed primary localized (less than four clock hours) OSSN treated with EXCRIM using adjuvant 0.02 % mitomycin-C (MMC) were included in the study. The main outcome measures were recurrence and complications related to MMC. The study enrolled 28 eyes of 28 patients with OSSN with a median age of 64.5 (range 43 to 84) years. The mean tumor size was 6.9 × 4.35 mm. There was corneal involvement in 23 of 28 (82 %). Seven patients (21 %) had delayed epithelial healing. Two of eight patients (25 %) with squamous cell carcinoma (SCC) had positive lateral margins. There were no recurrences over a mean follow-up of 49 months (range 24 to 96). The excision of OSSN combined with cryotherapy and intraoperative MMC is effective with a low recurrence rate. Long-term follow-up yielded favorable results.

Pathophysiology of ocular surface squamous neoplasia

PubMed Central

Gichuhi, Stephen; Ohnuma, Shin-ichi; Sagoo, Mandeep S.; Burton, Matthew J.

2014-01-01

The incidence of ocular surface squamous neoplasia (OSSN) is strongly associated with solar ultraviolet (UV) radiation, HIV and human papilloma virus (HPV). Africa has the highest incidence rates in the world. Most lesions occur at the limbus within the interpalpebral fissure particularly the nasal sector. The nasal limbus receives the highest intensity of sunlight. Limbal epithelial crypts are concentrated nasally and contain niches of limbal epithelial stem cells in the basal layer. It is possible that these are the progenitor cells in OSSN. OSSN arises in the basal epithelial cells spreading towards the surface which resembles the movement of corneo-limbal stem cell progeny before it later invades through the basement membrane below. UV radiation damages DNA producing pyrimidine dimers in the DNA chain. Specific CC → TT base pair dimer transformations of the p53 tumour-suppressor gene occur in OSSN allowing cells with damaged DNA past the G1-S cell cycle checkpoint. UV radiation also causes local and systemic photoimmunosuppression and reactivates latent viruses such as HPV. The E7 proteins of HPV promote proliferation of infected epithelial cells via the retinoblastoma gene while E6 proteins prevent the p53 tumour suppressor gene from effecting cell-cycle arrest of DNA-damaged and infected cells. Immunosuppression from UV radiation, HIV and vitamin A deficiency impairs tumour immune surveillance allowing survival of aberrant cells. Tumour growth and metastases are enhanced by; telomerase reactivation which increases the number of cell divisions a cell can undergo; vascular endothelial growth factor for angiogenesis and matrix metalloproteinases (MMPs) that destroy the intercellular matrix between cells. Despite these potential triggers, the disease is usually unilateral. It is unclear how HPV reaches the conjunctiva. PMID:25447808

Genetic Testing as a Tool to Identify Horses with or at Risk for Ocular Disorders.

PubMed

Bellone, Rebecca R

2017-12-01

Advances in equine genetics and genomics resources have enabled the understanding of some inherited ocular disorders and ocular manifestations. These ocular disorders include congenital stationary night blindness, equine recurrent uveitis, multiple congenital ocular anomalies, and squamous cell carcinoma. Genetic testing can identify horses with or at risk for disease and thus can assist in clinical management. In addition, genetic testing can identify horses that are carriers and thus can inform breeding decisions. Use of genetic tests in management and breeding decisions should aid in reducing the incidence of these disorders and improving the outcomes for horses at highest risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Pattern of ophthalmic lesions at two histopathology centres in Ethiopia.

PubMed

Assegid, A

2001-05-01

To describe the distribution of ocular, orbital and eyelid lesions that required histopathologic analysis in Ethiopian children and adults. A retrospective study. Tikur Anbessa and Menelik II Teaching hospitals, Addis Ababa, Ethiopia, during 1995 and 1999 period. Two hundred and ninety ophthalmic specimens were examined, 20% of which came from children. Half of the lesions had epithelial origin, about 30% were malignant, 22.6% were benign and 16.4% were potentially malignant. Squamous cell carcinoma was the leading conjunctival (26%), eyelid (33%), orbital (33%) and ocular (20%) lesion among adults and elderly people whereas only 6% of eyelid lesion were basal cell carcinomas. In children the most frequent intra-ocular as well as orbital tumour was retinoblastoma, 39%, followed by miscellaneous benign lesions (24%). More than half of the request forms were incomplete. In Addis Ababa, squamous cell carcinoma and retinoblastoma should be considered when evaluating ophthalmic lesions in adults and children, respectively. Clinicians and pathologists should improve their communication by filling in request forms, providing clear reports and making dialogue.

Clusterin in the eye: An old dog with new tricks at the ocular surface.

PubMed

Fini, M Elizabeth; Bauskar, Aditi; Jeong, Shinwu; Wilson, Mark R

2016-06-01

The multifunctional protein clusterin (CLU) was first described in 1983 as a secreted glycoprotein present in ram rete testis fluid that enhanced aggregation ('clustering') of a variety of cells in vitro. It was also independently discovered in a number of other systems. By the early 1990s, CLU was known under many names and its expression had been demonstrated throughout the body, including in the eye. Its homeostatic activities in proteostasis, cytoprotection, and anti-inflammation have been well documented, however its roles in health and disease are still not well understood. CLU is prominent at fluid-tissue interfaces, and in 1996 it was demonstrated to be the most highly expressed transcript in the human cornea, the protein product being localized to the apical layers of the mucosal epithelia of the cornea and conjunctiva. CLU protein is also present in human tears. Using a preclinical mouse model for desiccating stress that mimics human dry eye disease, the authors recently demonstrated that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration in the tears. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to LGALS3 (galectin-3), a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. CLU depletion from the ocular surface epithelia is seen in a variety of inflammatory conditions in humans and mice that lead to squamous metaplasia and a keratinized epithelium. This suggests that CLU might have a specific role in maintaining mucosal epithelial differentiation, an idea that can now be tested using the mouse model for desiccating stress. Most excitingly, the new findings suggest that CLU could serve as a novel biotherapeutic for dry eye disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Squamous cell carcinoma with sarcomatous stroma in the nasal cavity of a dog.

PubMed

Bosward, K L; Kessell, A E; Lucy, R J

2004-09-01

This is a report of an unusual squamous cell carcinoma in the nasal cavity of a dog. A 13-year-old Golden Retriever was presented with a unilateral nasal and ocular discharge. Although a nasal tumour was suspected, initial diagnostic investigations were unrewarding, and, with worsening clinical signs, the dog was euthanatized. Necropsy examination confirmed the presence of a nasal tumour that was composed histologically of both a well-differentiated squamous cell carcinoma component blending with a predominant spindle cell component. Immunohistochemical staining with anti-human keratin/cytokeratin (AE1/AE3, CAM 5.2 and broad spectrum cytokeratin), Vimentin, Desmin, smooth muscle actin and S-100 protein supported a diagnosis of a squamous cell carcinoma with (pseudo) sarcomatous stroma.

Topical chemotherapy for giant ocular surface squamous neoplasia of the conjunctiva and cornea: Is surgery necessary?

PubMed

Chaugule, Sonal S; Park, Jennifer; Finger, Paul T

2018-01-01

The purpose of this study is to report on the efficacy and safety of topical chemotherapy alone for giant ocular surface squamous neoplasia (OSSN). In this retrospective, interventional series, 10 eyes with giant OSSN underwent exfoliative biopsy to confirm the diagnosis followed by application of interferon alpha 2b (IFN α2b) and/or 5 fluorouracil, 1% (5FU). Reported outcome measures were tumor response, visual acuity, recurrence, systemic metastasis, and treatment complications. Ten patients (3 female, 7 male) had a mean age of 73 (median, 69; range 40-89) years. Mean tumor diameter was 13.1 (median, 12.3; range 8.2-19.4) mm. Five (50%) eyes were treated with IFN-α2b alone; 1 (10%) with 5-FU alone and 4 (40%) required both IFN-α2b and 5-FU. The mean duration of treatment was 3, 0.5, and 6.4 months for IFN-α2b alone, 5-FU alone, and both IFN-α2b and 5-FU respectively. Complete tumor response was observed in all 10 cases at mean follow-up of 12.8 (median, 11.5; range, 3-25) months. Complications noted were transient irritation and burning (n = 4), dry eyes (n = 2), and transient flu-like symptoms (n = 2). There was no evidence of chemotherapy-related symblepharon, stem cell deficiency, scleral thinning, or corneal opacity. There were no tumor recurrences, and no patient required surgical excision or cryotherapy. Topical chemotherapy was a safe and effective treatment, inducing complete regression in all cases of giant OSSN in this series. There were no sight-limiting complications.

9 CFR 314.11 - Handling of certain condemned products for purposes other than human food.

Code of Federal Regulations, 2010 CFR

2010-01-01

... INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY ORGANIZATION AND TERMINOLOGY; MANDATORY MEAT AND POULTRY... permission therefor is obtained from the circuit supervisor: Anasarca, Ocular Squamous Cell Carcinoma (after...

Correlation between the histological features of corneal surface pannus following ocular surface burns and the final outcome of cultivated limbal epithelial transplantation.

PubMed

Sati, Alok; Basu, Sayan; Sangwan, Virender S; Vemuganti, Geeta K

2015-04-01

To report the influence of histological features of corneal surface pannus following ocular surface burn on the outcome of cultivated limbal epithelial transplantation (CLET). On retrospectively reviewing the medical records of the patients who underwent autologous CLET from April 2002 to June 2012 at L V Prasad Eye Institute, Hyderabad, India, we could trace the histological reports in only 90 records. These 90 records, besides clinical parameters, were reviewed for the influence of various histological features on the final outcome of CLET. The histological features include epithelial hyperplasia (21.1%), surface ulceration (2.2%), goblet cells (62.2%), squamous metaplasia (11.1%), active fibrosis (31.1%), severe inflammation (8.9%), multinucleated giant cells (3.3%), stromal calcification (8.9%) and active proliferating vessels (5.6%). Among these histological features, patients with either hyperplasia or calcification in their excised corneal pannus show an unfavourable outcome compared with patients without hyperplasia (p=0.003) or calcification (p=0.018). A similar unfavourable outcome was not seen with other histological features and various clinical parameters. Presence of either calcific deposits or hyperplasia in the excised corneal pannus provides poor prognostication; hence, a proper counselling of such patients is mandatory along with a close follow-up. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The application of autologous serum eye drops in severe dry eye patients; subjective and objective parameters before and after treatment.

PubMed

Jirsova, Katerina; Brejchova, Kristyna; Krabcova, Ivana; Filipec, Martin; Al Fakih, Aref; Palos, Michalis; Vesela, Viera

2014-01-01

To assess the impact of autologous serum (AS) eye drops on the ocular surface of patients with bilateral severe dry eye and to draw a comparison between the clinical and laboratory examinations and the degree of subjective symptoms before and after serum treatment. A three-month prospective study was conducted on 17 patients with severe dry eye. AS eye drops were applied a maximum of 12 times a day together with regular therapy. Dry eye status was evaluated by clinical examination (visual acuity, Schirmer test, tear film breakup time, vital staining, tear film debris and meniscus), conjunctival impression cytology (epithelial and goblet cell density, snake-like chromatin, HLA-DR-positive and apoptotic cells) and subjectively by the patients. The application of AS eye drops led to a significant improvement in the Schirmer test (p < 0.01) and tear film debris (p < 0.05). The densities of goblet (p < 0.0001) and epithelial cells (p < 0.05) were significantly increased, indicating a decrease of squamous metaplasia after AS treatment. A significant decrease (p < 0.05) was found in the number of apoptotic, HLA-DR-positive and snake-like chromatin cells on the ocular surface. A significant improvement was found in all evaluated subjective symptoms. Altogether, the clinical results were improved in 77%, the laboratory results in 75% and the subjective feelings in 63% of the eyes. We found that three-month AS treatment led especially to the improvement of ocular surface dryness and damage of the epithelium. The improvement of dry eye after AS treatment correlated well with the clinical, laboratory and subjective findings. From the patients' subjective point of view, the positive effect of AS decreased with time, but still persisted up to three months after the end of therapy.

Effect of intermittent shear stress on corneal epithelial cells using an in vitro flow culture model.

PubMed

Hampel, Ulrike; Garreis, Fabian; Burgemeister, Fabian; Eßel, Nicole; Paulsen, Friedrich

2018-04-27

The aim of this study was to establish and to evaluate an in vitro model for culturing human telomerase-immortalized corneal epithelial (hTCEpi) cells under adjustable medium flow mimicking the movements of the tear film on the ocular surface. Using an IBIDI pump system, cells were cultured under unidirectional, continuous or oscillating, discontinuous medium flow. Cell surface and cytoskeletal architecture were investigated by scanning electron microscopy and immunofluorescence. Gene expression of e-cadherin, occludin, tight junction protein (TJP), desmoplakin, desmocollin and mucins was investigated by real-time PCR. Protein expression of desmoplakin, TJP, occludin and e-cadherin was analyzed by western blot and localization was detected by immunofluorescence. Rose bengal staining was used to assess mucin (MUC) barrier integrity. MUC1, -4 and -16 proteins were localized by immunofluorescence. Medium flow-induced shear stress dramatically changed cellular morphology of hTCEpi. Cells subjected to discontinuous shear stress displayed the typical flattened, polygonal cell shape of the superficial layer of stratified squamous epithelia. Cell surfaces showed less bulging under shear stress and less extracellular gaps. The mRNA expression of E-cadherin, occludin and TJP were increased under oscillatory medium flow. Desmoplakin and occludin protein were upregulated under oscillatory shear stress. Stress fiber formation was not aligned to flow direction. MUC1, -4, and -16 protein were localized under all culture conditions, a regulation on mRNA expression was not detectable. Rose Bengal uptake was diminished under unidirectional conditions. Our findings suggest that shear stress as it occurs at the ocular surface during blinking exerts marked effects on corneal epithelial cells, such as changes in cellular morphology and expression of cell junctions. The described model may be useful for in vitro investigations of ocular surface epithelia as it represents a much more physiologic reproduction of the in vivo situation than the commonly applied static culture conditions. Copyright © 2018. Published by Elsevier Inc.

Ocular squamous cell carcinoma in Holstein cows from the South of Brazil

PubMed Central

Fornazari, Gabrielle A.; Kravetz, Juliana; Kiupel, Matti; Sledge, Dodd; Filho, Ivan Roque De Barros; Montiani-Ferreira, Fabiano

2017-01-01

Aim: The aim of this study was to investigate 10 cases of bovine ocular squamous cell carcinoma (OSCC) diagnosed in Holstein or Holstein-crosses cows. Materials and Methods: The investigation was performed exclusively in OSCC cases diagnosed in the State of Paraná and Santa Catarina. A combination of two previously existing histopathological classifications systems was used. The tissue samples were tested for immunoexpression of p53 and p16 and polymerase chain reaction (PCR) for bovine herpesvirus and papillomavirus. Results: A positive correlation between number of mitotic figures and tissue invasion was found. Anaplasia parameters did not correlate well with tumor invasion of deeper tissues and mitotic counts. Six of 10 OSCC cases were in animals with heavily pigmented eyes. Immunoexpression of p53 and p16 was observed in 3 cases each. Bovine herpesvirus and papillomavirus were not detected by PCR. Conclusions: Our results indicate that OSCC occurrence is most likely multifactorial with genetic, phenotypic, and environmental influences contributing to the pathogenesis of the disease. PMID:29391681

Ocular surface squamous neoplasia in HIV-infected patients: current perspectives.

PubMed

Rathi, Shweta Gupta; Ganguly Kapoor, Anasua; Kaliki, Swathi

2018-01-01

Ocular surface squamous neoplasia (OSSN) refers to a spectrum of conjunctival and corneal epithelial tumors including dysplasia, carcinoma in situ, and invasive carcinoma. In this article, we discuss the current perspectives of OSSN associated with HIV infection, focusing mainly on the epidemiology, pathophysiology, clinical manifestations, diagnosis, and treatment of these tumors in patients with HIV. Upsurge in the incidence of OSSN with the HIV pandemic most severely affected sub-Saharan Africa, due to associated risk factors, such as human papilloma virus and solar ultraviolet exposure. OSSN has been reported as the first presenting sign of HIV/AIDS in 26%-86% cases, and seropositivity is noted in 38%-92% OSSN patients. Mean age at presentation of OSSN has dropped to the third to fourth decade in HIV-positive patients in developing countries. HIV-infected patients reveal large aggressive tumors, higher-grade malignancy, higher incidence of corneal, scleral, and orbital invasion, advanced-stage T4 tumors, higher need for extended enucleation/exenteration, and increased risk of tumor recurrence. Current management of OSSN in HIV-positive individuals is based on standard treatment guidelines described for OSSN in the general population, as there is little information available about various treatment modalities or their outcomes in patients with HIV. OSSN can occur at any time in the disease course of HIV/AIDS, and no significant trend has been discovered between CD4 count and grade of OSSN. Furthermore, the effect of highly active antiretroviral therapy on OSSN is controversial. The current recommendation is to conduct HIV screening in all cases presenting with OSSN to rule out undiagnosed HIV infection. Patient counseling is crucial, with emphasis on regular follow-up to address high recurrence rates and early presentation to an ophthalmologist for of any symptoms in the unaffected eye. Effective evidence-based interventions are needed to allow early diagnosis and treatment, as well as prevention of the disease.

Orbital amelanotic melanoma in xeroderma pigmentosum: A rare association

PubMed Central

Amitava, Abadan K; Mehdi, Ghazala; Sharma, Rajeev; Alam, Mohammad S

2008-01-01

Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder of DNA repair in which the body′s normal ability to repair damage caused by ultraviolet light is deficient. This leads to a 1000-fold increased risk of cutaneous and ocular neoplasms. Ocular neoplasms occurring in XP in order of frequency are squamous cell carcinoma, basal cell carcinoma and melanoma. Malignant melanomas occur at an early age in patients with XP. We report a case of XP with massive orbital melanoma in an eight-year-old boy which is unique due to its amelanotic presentation confirmed histopathologically. PMID:18711275

Coexistence of salivary gland cysticercosis with squamous cell carcinoma of the mandible.

PubMed

Mahajan, Dipti; Khurana, Nita; Setia, Namrata

2007-03-01

Cysticercosis is a parasitic infestation caused by the pork tapeworm larval stage, Cysticercus cellulosae. The majority of the cases present in ocular, cerebral, and subcutaneous locations. We report the presence of cysticercosis inside the submandibular gland in association with squamous cell carcinoma of the inferior alveolar ramus of the mandible. To the best of our knowledge, this is the first case report documenting cysticercosis inside a salivary gland. A 65-year-old male presented with complaints of an ulcerative lesion on the inferior alveolar ramus present for 2 months. Histological examination revealed a keratinizing well-differentiated squamous cell carcinoma involving the alveolar margin and mandible. The histopathological examination of the submandibular gland revealed cysticercosis. This case emphasizes the importance of adequate sampling of all the tissues obtained for associated infectious disorders, more so in immunosuppressed patients, which will help the clinician to manage the case appropriately.

Management of the ocular surface and tear film before, during, and after laser in situ keratomileusis.

PubMed

Albietz, Julie M; Lenton, Lee M

2004-01-01

To identify evidence-based, best practice strategies for managing the ocular surface and tear film before, during, and after laser in situ keratomileusis (LASIK). After a comprehensive review of relevant published literature, evidence-based recommendations for best practice management strategies are presented. Symptoms of ocular irritation and signs of dysfunction of the integrated lacrimal gland/ocular surface functional gland unit are common before and after LASIK. The status of the ocular surface and tear film before LASIK can impact surgical outcomes in terms of potential complications during and after surgery, refractive outcome, optical quality, patient satisfaction, and the severity and duration of dry eye after LASIK. Before LASIK, the health of the ocular surface should be optimized and patients selected appropriately. Dry eye before surgery and female gender are risk factors for developing chronic dry eye after LASIK. Management of the ocular surface during LASIK can minimize ocular surface damage and the risk of adverse outcomes. Long-term management of the tear film and ocular surface after LASIK can reduce the severity and duration of dry eye symptoms and signs. Strategies to manage the integrated ocular surface/lacrimal gland functional unit before, during, and after LASIK can optimize outcomes. As problems with the ocular surface and tear film are relatively common, attention should focus on the use and improvement of evidence-based management strategies.

The role of microbial flora on the ocular surface.

PubMed

Miller, Darlene; Iovieno, Alfonso

2009-10-01

Presence and interplay of microbial flora at the ocular surface reveal dynamic and evolving interactions with implications for both ocular surface health and disease. Data in this area are scarce or non-existent. The purpose of this review is to provide a snapshot of new and emerging developments in this area over the last 12 months. Recent findings signal potential roles for ocular surface microbial flora in both the preservation and extension of ocular surface health and in the initiation of new or escalation of common surface disorders. Contributions range from priming surface epithelial immune cells to regulating mucin composition and production. Other findings explore the emergent role of ocular microbial flora cross talk with pattern recognition receptors to protect and strengthen local and adaptive mucosal immunity while preserving vision. Deciphering the functional role of microbial communities at the ocular surface could bring new insights into and clarify the epidemiology and pathology of ocular surface dynamics in health and disease.

Surgical versus Medical Treatment of Ocular Surface Squamous Neoplasia: A Cost Comparison.

PubMed

Moon, Christina S; Nanji, Afshan A; Galor, Anat; McCollister, Kathryn E; Karp, Carol L

2016-03-01

The objective of this study was to compare the cost associated with surgical versus interferon-alpha 2b (IFNα2b) treatment for ocular surface squamous neoplasia (OSSN). A matched, case-control study. A total of 98 patients with OSSN, 49 of whom were treated surgically and 49 of whom were treated medically. Patients with OSSN treated with IFNα2b were matched to patients treated with surgery on the basis of age and date of treatment initiation. Financial cost to the patient was calculated using 2 different methods (hospital billing and Medicare allowable charges) and compared between the 2 groups. These fees included physician fees (clinic, pathology, anesthesia, and surgery), facility fees (clinic, pathology, and operating room), and medication costs. Time invested by patients was calculated in terms of number of visits to the hospital and compared between the 2 groups. Parking costs, transportation, caregiver wages, and lost wages were not considered in our analysis. Number of clinic visits and cost of therapy as represented by both hospital charges and Medicare allowable charges. When considering cost in terms of time, the medical group had an average of 2 more visits over 1 year compared with the surgical group. Cost as represented by hospital charges was higher in the surgical group (mean, $17 598; standard deviation [SD], $7624) when compared with the IFNα2b group (mean, $4986; SD, $2040). However, cost between the 2 groups was comparable when calculated on the basis of Medicare allowable charges (surgical group: mean, $3528; SD, $1610; medical group: mean, $2831; SD, $1082; P = 1.00). The highest cost in the surgical group was the excisional biopsy (hospital billing $17 598; Medicare allowable $3528), and the highest cost in the medical group was interferon ($1172 for drops, average 8.0 bottles; $370 for injections, average 5.4 injections). Our data in this group of patients previously demonstrated equal efficacy of surgical versus medical treatment. In this article, we consider costs of therapy and found that medical treatment involved two more office visits, whereas surgical treatment could be more or equally costly depending on insurance coverage. Copyright © 2016 American Academy of Ophthalmology. All rights reserved.

Recombinant interferon alpha 2b for ocular surface squamous neoplasia: An efficient and cost-effective treatment modality in Asian Indian patients

PubMed Central

Kaliki, Swathi; Singh, Swati; Iram, Sadiya; Tripuraneni, Dharani

2016-01-01

Purpose: The purpose was to study the efficacy of interferon alpha 2b (INF α2b) in the treatment of ocular surface squamous neoplasia (OSSN) and analyze its cost-effectiveness in India. Study Design: This was a retrospective study of thirty patients with OSSN treated with topical INF α2b (1 MIU/cc) ± perilesional INF α2b (5 MIU/cc). Results: The tumor involved cornea (n = 9, 30%), conjunctivo-limbal-corneal surface (n = 19, 63%), or bulbar conjunctiva (n = 2, 7%). The mean basal dimension of the tumor was 16 mm. The tumors belonged to Tis (n = 6, 20%) or T3 (n = 24, 80%) based on the American Joint Committee Classification, 7th edition. In the six patients with Tis, three cycles of topical INF α2b were used for immunoprevention. In the remaining 24 patients, INF α2b was advised for immunoreduction, but served as immunotherapy with 100% tumor regression in 22 (92%) cases, and resulted in 95% immunoreduction in 2 (6%) cases. Complete tumor regression by immunotherapy (n = 22) was achieved with a mean number of three topical INF α2b cycles and two perilesional injections. All these 22 patients received three additional topical INF α2b cycles after complete tumor regression. For immunoreduction (n = 2), both patients received six cycles of topical INF α2b which was three perilesional INF α2b injections. The mean total treatment cost per patient with INF α2b was INR 9164 ($US 137). Based on maximum basal diameter of tumor at presentation, the mean total treatment cost per patient with INF α2b was INR 4866 ($US 73) for eyes with microscopic evidence of tumor residue (n = 6), INR 9607 ($US 143) for tumors ≤10 mm (n = 13), and INR 10,985 ($US 164) for tumors >10 mm (n = 11), with two patients needing additional surgical excision for complete tumor control. Conclusion: INF α2b can be used for immunoreduction, immunotherapy, or immunoprevention of OSSN. INF α2b is a cost-effective treatment modality for OSSN at an average total treatment cost of INR 9164 ($US 137) per patient. PMID:27905329

Recombinant interferon alpha 2b for ocular surface squamous neoplasia: An efficient and cost-effective treatment modality in Asian Indian patients.

PubMed

Kaliki, Swathi; Singh, Swati; Iram, Sadiya; Tripuraneni, Dharani

2016-10-01

The purpose was to study the efficacy of interferon alpha 2b (INF α2b) in the treatment of ocular surface squamous neoplasia (OSSN) and analyze its cost-effectiveness in India. This was a retrospective study of thirty patients with OSSN treated with topical INF α2b (1 MIU/cc) ± perilesional INF α2b (5 MIU/cc). The tumor involved cornea (n = 9, 30%), conjunctivo-limbal-corneal surface (n = 19, 63%), or bulbar conjunctiva (n = 2, 7%). The mean basal dimension of the tumor was 16 mm. The tumors belonged to Tis (n = 6, 20%) or T3 (n = 24, 80%) based on the American Joint Committee Classification, 7th edition. In the six patients with Tis, three cycles of topical INF α2b were used for immunoprevention. In the remaining 24 patients, INF α2b was advised for immunoreduction, but served as immunotherapy with 100% tumor regression in 22 (92%) cases, and resulted in 95% immunoreduction in 2 (6%) cases. Complete tumor regression by immunotherapy (n = 22) was achieved with a mean number of three topical INF α2b cycles and two perilesional injections. All these 22 patients received three additional topical INF α2b cycles after complete tumor regression. For immunoreduction (n = 2), both patients received six cycles of topical INF α2b which was three perilesional INF α2b injections. The mean total treatment cost per patient with INF α2b was INR 9164 ($US 137). Based on maximum basal diameter of tumor at presentation, the mean total treatment cost per patient with INF α2b was INR 4866 ($US 73) for eyes with microscopic evidence of tumor residue (n = 6), INR 9607 ($US 143) for tumors ≤10 mm (n = 13), and INR 10,985 ($US 164) for tumors >10 mm (n = 11), with two patients needing additional surgical excision for complete tumor control. INF α2b can be used for immunoreduction, immunotherapy, or immunoprevention of OSSN. INF α2b is a cost-effective treatment modality for OSSN at an average total treatment cost of INR 9164 ($US 137) per patient.

The pathology of dry eye: the interaction between the ocular surface and lacrimal glands.

PubMed

Stern, M E; Beuerman, R W; Fox, R I; Gao, J; Mircheff, A K; Pflugfelder, S C

1998-11-01

Most dry-eye symptoms result from an abnormal, nonlubricative ocular surface that increases shear forces under the eyelids and diminishes the ability of the ocular surface to respond to environmental challenges. This ocular-surface dysfunction may result from immunocompromise due to systemic autoimmune disease or may occur locally from a decrease in systemic androgen support to the lacrimal gland as seen in aging, most frequently in the menopausal female. Components of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland, and interconnecting innervation act as a functional unit. When one portion is compromised, normal lacrimal support of the ocular surface is impaired. Resulting immune-based inflammation can lead to lacrimal gland and neural dysfunction. This progression yields the OS symptoms associated with dry eye. Restoration of lacrimal function involves resolution of lymphocytic activation and inflammation. This has been demonstrated in the MRL/lpr mouse using systemic androgens or cyclosporine and in the dry-eye dog using topical cyclosporine. The efficacy of cyclosporine may be due to its immunomodulatory and antiinflammatory (phosphatase inhibitory capability) functions on the ocular surface, resulting in a normalization of nerve traffic. Although the etiologies of dry eye are varied, common to all ocular-surface disease is an underlying cytokine/receptor-mediated inflammatory process. By treating this process, it may be possible to normalize the ocular surface/lacrimal neural reflex and facilitate ocular surface healing.

Ocular surface injury from a microwave superheated egg resulting in a pseudopterygium.

PubMed

Gagnon, Michael R; Dickinson, Paul J

2005-05-01

To describe the first case of ocular surface injury resulting in a pseudopterygium from a microwave superheated egg. Case report. A 12-year-old girl sustained an ocular surface injury resulting in a pseudopterygium from a microwave superheated egg. Microwave superheated eggs can result in ocular injury. This case illustrates the potential ocular danger involved with microwave ovens.

Ocular Safety of Topical Naltrexone

DTIC Science & Technology

2013-04-01

prescription medicines , vitamins and herbal supplements. Especially tell your doctor if you take any opioid-containing medicines for pain, cough, or...squamous cell carcinoma. International Journal of Molecular Medicine 2000;5:191-6. 13. Zagon IS, McLaughlin PJ. Naloxone prolongs the survival time of mice...human pancreatic adenocarcinoma. International Journal of Molecular Medicine 2000;5:77-84. 18 35. Zagon IS, Verderame MF, Zimmer WE, McLaughlin PJ

The tear film and ocular mucins.

PubMed

Davidson, Harriet J; Kuonen, Vanessa J

2004-01-01

Abstract The trilaminar tear film, composed of the lipid, aqueous and mucin layers, has many functions including defending the ocular surface. The aqueous layer has several soluble antimicrobial factors that protect the ocular surface. Ocular mucins have recently been studied with regard to their role in the defense of the eye as well as in dry eye syndromes. To date, 15 mucin genes have been identified, and six of these mucin genes are localized to or secreted by ocular glands or epithelia. Understanding the production, secretion and function of ocular mucins will aid in the treatment of dry eye syndromes and ocular surface microbial infections.

The mucosal surfaces of both eyes are immunologically linked by a neurogenic inflammatory reflex involving TRPV1 and substance P.

PubMed

Guzmán, Mauricio; Miglio, Maximiliano S; Zgajnar, Nadia R; Colado, Ana; Almejún, María B; Keitelman, Irene A; Sabbione, Florencia; Fuentes, Federico; Trevani, Analía S; Giordano, Mirta N; Galletti, Jeremías G

2018-06-04

Immunological interdependence between the two eyes has been reported for the cornea and the retina but not for the ocular mucosal surface. Intriguingly, patients frequently report ocular surface-related symptoms in the other eye after unilateral ocular surgery. Here we show how unilateral eye injuries in mice affect the mucosal immune response of the opposite ocular surface. We report that, despite the lack of lymphatic cross-drainage, a neurogenic inflammatory reflex in the contralateral conjunctiva is sufficient to increase, first, epithelial nuclear factor kappa B signaling, then, dendritic cell maturation, and finally, expansion of effector, instead of regulatory, T cells in the draining lymph node, leading to disrupted ocular mucosal tolerance. We also show that damage to ocular surface nerves is required. Using pharmacological inhibitors and agonists, we identified transient receptor potential vanilloid 1 (TRPV1) channel as the receptor sensing tissue damage in the injured eye and substance P released in the opposite ocular surface as the effector of the sympathetic response. Finally, blocking either step prevented subsequent ocular allergic reactions in the opposite eye in a unilateral corneal alkali burn model. This study demonstrates that both ocular surfaces are immunologically linked and suggests potential therapeutic targets for intervention.

Rebamipide suppresses PolyI:C-stimulated cytokine production in human conjunctival epithelial cells.

PubMed

Ueta, Mayumi; Sotozono, Chie; Yokoi, Norihiko; Kinoshita, Shigeru

2013-09-01

We previously documented that ocular surface epithelial cells could regulate ocular surface inflammation and suggested that, while Toll-like receptor 3 upregulates, EP3, one of the prostaglandin E2 receptors, downregulates ocular surface inflammation. Others reported that rebamipide, a gastroprotective drug, could not only increase the gastric mucus production, but also suppressed gastric mucosal inflammation and that it was dominantly distributed in mucosal tissues. The eyedrop form of rebamipide, approved in Japan for use in the treatment of dry eye diseases, upregulates mucin secretion and production, thereby suppressing superficial punctate keratopathy on the ocular surface of patients with this disease. In the current study, we investigated whether rebamipide has anti- inflammatory effects on the ocular surface. To examine the effects of rebamipide on polyI:C-induced cytokine expression by primary human conjunctival epithelial cells, we used enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction assay. We studied the effects of rebamipide on ocular surface inflammation in our murine experimental allergic conjunctivitis (EAC) model. Rebamipide could suppress polyI:C-induced cytokine production and the expression of mRNAs for CXCL10, CXCL11, RANTES, MCP-1, and IL-6 in human conjunctival epithelial cells. In our EAC model, the topical administration of rebamipide suppressed conjunctival allergic eosinophil infiltration. The topical application of rebamipide on the ocular surface might suppress ocular surface inflammation by suppressing the production of cytokines by ocular surface epithelial cells.

Emerging treatment paradigms of ocular surface disease: proceedings of the Ocular Surface Workshop.

PubMed

Rolando, M; Geerling, G; Dua, H S; Benítez-del-Castillo, J M; Creuzot-Garcher, C

2010-01-01

The objective of the Ocular Surface Workshop in Rome, Italy, on 6 February 2009, was to enhance the understanding of ocular surface disease (OSD) through an exploration of the nature of its complexities and current treatment paradigms across Europe. It was hoped that the peer-to-peer discussions and updates regarding common knowledge, clinical practices and shared experiences at this workshop would subsequently shape future treatment approaches to OSD.

Ocular surface injury from a microwave superheated liquid.

PubMed

Gagnon, Michael R; Walter, Keith A

2004-03-01

To describe the ocular surface injury resulting from a microwave superheated liquid. Case report. A 40-year-old man sustained an ocular surface injury from a microwave superheated liquid. The injury resulted in limbal stem cell damage requiring an autograft limbal stem cell transplantation. We are unaware of previous reports of microwave superheated liquids resulting in ocular injury. Microwave superheating of liquids is a potential ocular danger that should be brought to the attention of both ophthalmologists and their patients.

In utero eyeball development study by magnetic resonance imaging.

PubMed

Brémond-Gignac, D S; Benali, K; Deplus, S; Cussenot, O; Ferkdadji, L; Elmaleh, M; Lassau, J P

1997-01-01

The aim of this study was to measure fetal ocular development and to determine a growth curve by means of measurements in utero. Fetal ocular development was recorded by analysis of the results of magnetic resonance imaging (MRI). An anatomic study allowed definition of the best contrasted MRI sequences for calculation of the ocular surface. Biometric analysis of the values of the ocular surface in the neuro-ocular plane in 35 fetuses allowed establishment of a linear model of ocular growth curve in utero. Evaluation of ocular development may allow the detection and confirmation of malformational ocular anomalies such as microphthalmia.

Control of Cross Talk between Angiogenesis and Inflammation by Mesenchymal Stem Cells for the Treatment of Ocular Surface Diseases.

PubMed

Li, Fei; Zhao, Shao-Zhen

2016-01-01

Angiogenesis is beneficial in the treatment of ischemic heart disease and peripheral artery disease. However, it facilitates inflammatory cell filtration and inflammation cascade that disrupt the immune and angiogenesis privilege of the avascular cornea, resulting in ocular surface diseases and even vision loss. Although great progress has been achieved, healing of severe ocular surface injury and immunosuppression of corneal transplantation are the most difficult and challenging step in the treatment of ocular surface disorders. Mesenchymal stem cells (MSCs), derived from various adult tissues, are able to differentiate into different cell types such as endothelial cells and fat cells. Although it is still under debate whether MSCs could give rise to functional corneal cells, recent results from different study groups showed that MSCs could improve corneal disease recovery through suppression of inflammation and modulation of immune cells. Thus, MSCs could become a promising tool for ocular surface disorders. In this review, we discussed how angiogenesis and inflammation are orchestrated in the pathogenesis of ocular surface disease. We overviewed and updated the knowledge of MSCs and then summarized the therapeutic potential of MSCs via control of angiogenesis, inflammation, and immune response in the treatment of ocular surface disease.

[Study of ocular surface electromyography signal analysis].

PubMed

Zhu, Bei; Qi, Li-Ping

2009-11-01

Test ocular surface electromyography signal waves and characteristic parameters to provide effective data for the diagnosis and treatment of ocular myopathy. Surface electromyography signals tests were performed in 140 normal volunteers and 30 patients with ophthalmoplegia. Surface electrodes were attached to medial canthi, lateral canthi and the middle of frontal bone. Then some alternate flashing red lamps were installed on perimeter to reduce the movement of eyeball. The computer hardware, software, and A/D adapter (12 Bit) were used. Sampling frequency could be selected within 40 kHz, frequency of amplifier was 2 kHz, and input short circuit noise was less than 3 microV. For normal volunteers, the ocular surface electromyography signals were regular, and the electric waves were similar between different sex groups and age groups. While for patients with ophthalmoplegia, the wave amplitude of ocular surface electromyography signals were declined or disappeared in the dyskinesia direction. The wave amplitude was related with the degree of pathological process. The characteristic parameters of patients with ophthalmoplegia were higher than normal volunteers. The figures of ocular surface electromyogram obtained from normal volunteers were obviously different with that from patients with ophthalmoplegia. This test can provide reliable quantized data for the diagnosis and treatment of ocular myopathy.

Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye

PubMed Central

Bauskar, Aditi; Mack, Wendy J.; Mauris, Jerome; Argüeso, Pablo; Heur, Martin; Nagel, Barbara A.; Kolar, Grant R.; Gleave, Martin E.; Nakamura, Takahiro; Kinoshita, Shigeru; Moradian-Oldak, Janet; Panjwani, Noorjahan; Pflugfelder, Stephen C.; Wilson, Mark R.; Fini, M. Elizabeth; Jeong, Shinwu

2015-01-01

Dry eye is a common disorder caused by inadequate hydration of the ocular surface that results in disruption of barrier function. The homeostatic protein clusterin (CLU) is prominent at fluid-tissue interfaces throughout the body. CLU levels are reduced at the ocular surface in human inflammatory disorders that manifest as severe dry eye, as well as in a preclinical mouse model for desiccating stress that mimics dry eye. Using this mouse model, we show here that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to the galectin LGALS3, a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. These findings define a fundamentally new mechanism for ocular surface protection and suggest CLU as a biotherapeutic for dry eye. PMID:26402857

Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye.

PubMed

Bauskar, Aditi; Mack, Wendy J; Mauris, Jerome; Argüeso, Pablo; Heur, Martin; Nagel, Barbara A; Kolar, Grant R; Gleave, Martin E; Nakamura, Takahiro; Kinoshita, Shigeru; Moradian-Oldak, Janet; Panjwani, Noorjahan; Pflugfelder, Stephen C; Wilson, Mark R; Fini, M Elizabeth; Jeong, Shinwu

2015-01-01

Dry eye is a common disorder caused by inadequate hydration of the ocular surface that results in disruption of barrier function. The homeostatic protein clusterin (CLU) is prominent at fluid-tissue interfaces throughout the body. CLU levels are reduced at the ocular surface in human inflammatory disorders that manifest as severe dry eye, as well as in a preclinical mouse model for desiccating stress that mimics dry eye. Using this mouse model, we show here that CLU prevents and ameliorates ocular surface barrier disruption by a remarkable sealing mechanism dependent on attainment of a critical all-or-none concentration. When the CLU level drops below the critical all-or-none threshold, the barrier becomes vulnerable to desiccating stress. CLU binds selectively to the ocular surface subjected to desiccating stress in vivo, and in vitro to the galectin LGALS3, a key barrier component. Positioned in this way, CLU not only physically seals the ocular surface barrier, but it also protects the barrier cells and prevents further damage to barrier structure. These findings define a fundamentally new mechanism for ocular surface protection and suggest CLU as a biotherapeutic for dry eye.

Toluidine Blue 0.05% Vital Staining for the Diagnosis of Ocular Surface Squamous Neoplasia in Kenya.

PubMed

Gichuhi, Stephen; Macharia, Ephantus; Kabiru, Joy; Zindamoyen, Alain M'bongo; Rono, Hilary; Ollando, Ernest; Wanyonyi, Leonard; Wachira, Joseph; Munene, Rhoda; Onyuma, Timothy; Jaoko, Walter G; Sagoo, Mandeep S; Weiss, Helen A; Burton, Matthew J

2015-11-01

Clinical features are unreliable for distinguishing ocular surface squamous neoplasia (OSSN) from benign conjunctival lesions. To evaluate the adverse effects, accuracy, and interobserver variation of toluidine blue 0.05% vital staining in distinguishing OSSN, confirmed by histopathology, from other conjunctival lesions. Cross-sectional study in Kenya from July 2012 through July 2014 of 419 adults with suspicious conjunctival lesions. Pregnant and breastfeeding women were excluded. Comprehensive ophthalmic slitlamp examination was conducted. Vital staining with toluidine blue 0.05% aqueous solution was performed before surgery. Initial safety testing was conducted on large tumors scheduled for exenteration looking for corneal toxicity on histology before testing smaller tumors. We asked about pain or discomfort after staining and evaluated the cornea at the slitlamp for epithelial defects. Lesions were photographed before and after staining. Diagnosis was confirmed by histopathology. Six examiners assessed photographs from a subset of 100 consecutive participants for staining and made a diagnosis of OSSN vs non-OSSN. Staining was compared with histopathology to estimate sensitivity, specificity, and predictive values. Adverse effects were enumerated. Interobserver agreement was estimated using the κ statistic. A total of 143 of 419 participants (34%) had OSSN by histopathology. The median age of all participants was 37 years (interquartile range, 32-45 years) and 278 (66%) were female. A total of 322 of the 419 participants had positive staining while 2 of 419 were equivocal. There was no histological evidence of corneal toxicity. Mild discomfort was reported by 88 (21%) and mild superficial punctate keratopathy seen in 7 (1.7%). For detecting OSSN, toluidine blue had a sensitivity of 92% (95% CI, 87%-96%), specificity of 31% (95% CI, 25%-36%), positive predictive value of 41% (95% CI, 35%-46%), and negative predictive value of 88% (95% CI, 80%-94%). Interobserver agreement was substantial for staining (κ = 0.76) and moderate for diagnosis (κ = 0.40). With the high sensitivity and low specificity for OSSN compared with histopathology among patients with conjunctival lesions, toluidine blue 0.05% vital staining is a good screening tool. However, it is not a good diagnostic tool owing to a high frequency of false-positives. The high negative predictive value suggests that a negative staining result indicates that OSSN is relatively unlikely.

[Ocular surface system integrity].

PubMed

Safonova, T N; Pateyuk, L S

2015-01-01

The interplay of different structures belonging to either the anterior segment of the eye or its accessory visual apparatus, which all share common embryological, anatomical, functional, and physiological features, is discussed. Explanation of such terms, as ocular surface, lacrimal functional unit, and ocular surface system, is provided.

Xeroderma pigmentosum: a case report and review of the literature.

PubMed

Feller, L; Wood, N H; Motswaledi, M H; Khammissa, R A G; Meyer, M; Lemmer, J

2010-06-01

Inherited molecular defects in nucleotide excision repair genes cause the autosomal recessive condition xeroderma pigmentosum. Xeroderma pigmentosum is characterized by photo-hypersensitivity of sun-exposed tissues, and by a several thousand-fold increase in the risk of developing malignant neoplasms of the skin and of the eyes. Mutations in xeroderma pigmentosum genes that regulate nucleotide excision repair, not only predispose persons with xeroderma pigmentosum to multiple malignancies, but also promote premature cutaneous and ocular ageing, and in some cases promote progressive neurodegenerative changes. This paper describes a case of xeroderma pigmentosum with advanced cutaneous squamous cell carcinoma, actinic cheilitis and ocular lesions in a 19-year-old black woman. The extensive ultraviolet radiation-induced skin and eye damage are evidence of neglect of sun-protection and lack of appropriate medical care from childhood.

Extraocular Sebaceous Carcinoma on the Chest Wall – A Case Report

PubMed Central

SR, Diwakar; Thulasi, Vasudevaiah; Shenoy, K Manjunath

2014-01-01

Sebaceous carcinoma is a rare aggressive skin cancer derived from the epithelium of sebaceous glands. Sebaceous carcinomas are generally divided as ocular or extraocular locations. Very few cases of extra ocular sebaceous carcinomas have been reported till date. Among them only six cases were reported which were on the chest wall. We are hereby reporting the seventh case of sebaceous carcinoma on the chest wall. The disease exhibits diverse clinical presentations and histologic patterns, often resulting in a delay in an accurate diagnosis as it may mimic many other cutaneous malignancies like Dermatofibrosarcoma protuberance Basal Cell Carcinoma or Squamous Cell Carcinoma. High degree of suspicion is required and sebaceous carcinoma should be considered as one of the differential diagnosis for an ulceroproliferative growth on the skin. PMID:25121026

Functions of ocular surface mucins in health and disease

PubMed Central

Mantelli, Flavio; Argüeso, Pablo

2009-01-01

Purpose of review The purpose of the present review is to describe new concepts on the role of mucins in the protection of corneal and conjunctival epithelia and to identify alterations of mucins in ocular surface diseases. Recent findings New evidence indicates that gel-forming and cell surface-associated mucins contribute differently to the protection of the ocular surface against allergens, pathogens, extracellular molecules, abrasive stress, and drying. Summary Mucins are high molecular weight glycoproteins characterized by their extensive O-glycosylation. Major mucins expressed by the ocular surface epithelia include cell surface-associated mucins MUC1, -4 and -16, and the gel-forming mucin MUC5AC. Recent advances using functional assays have allowed the examination of their roles in the protection of corneal and conjunctival epithelia. Alterations in mucin and mucin O-glycan biosynthesis in ocular surface disorders, including allergy, non-autoimmune dry eye, autoimmune dry eye, and infection, are presented. PMID:18769205

Efficacy of plasma rich in growth factors for the treatment of dry eye.

PubMed

López-Plandolit, Silvia; Morales, María-Celia; Freire, Vanesa; Grau, Arturo E; Durán, Juan A

2011-12-01

To evaluate the efficacy of plasma rich in growth factors (PRGF) for the treatment of moderate/severe dry eye. PRGF treatment was administered to 16 patients who had moderate/severe dry eye diagnosed and who had not responded previously to other standard treatments. We quantified several growth factors present in the PRGF of each patient and obtained quantitative registers of the symptoms (modified score dry eye questionnaire), both before and after PRGF treatment. We also performed impression cytology to determine the degree of squamous metaplasia before and after PRGF treatment. PRGF treatment was associated with a statistically significant improvement in score dry eye questionnaire values (P < 0.001). Results from impression cytology corroborated this improvement, but the reduction in the degree of squamous metaplasia was not statistically significant. In 75% of patients treated with PRGF, no further treatments were required, whereas in the remaining 25% other ocular treatments could be reduced. PRGF led to symptom improvement in patients with moderate/severe dry eye. Surprisingly, the symptoms recorded in the dry eye questionnaire do not always agree with the degree of squamous metaplasia measured by impression cytology.

Effects of ocular surface strontium-90 beta radiotherapy in dogs latently infected with canine herpesvirus-1.

PubMed

Nicklin, Amanda M; McEntee, Margaret C; Ledbetter, Eric C

2014-12-05

Latent canine herpesvirus-1 (CHV-1) infections are common in domestic dogs, but stimuli causing viral reactivation and recrudescent disease are poorly understood. Immunosuppressive pharmaceuticals are currently the only experimentally established triggers for recurrent ocular CHV-1 infection in dogs; however, ocular CHV-1 shedding has been reported clinically following strontium-90 beta radiotherapy of the ocular surface and it has been speculated that radiotherapy can directly induce viral reactivation. Strontium-90 is used as a beta radiation source for the treatment of a variety of neoplastic and immune-mediated canine ocular surface diseases. In the present study, the effects of ocular surface strontium-90 beta radiotherapy in dogs latently infected with CHV-1 were evaluated. Ten mature dogs with experimentally induced latent CHV-1 infections were randomly divided into two groups: one group received a single fraction 50 Gy radiation dose in one application from a strontium-90 ophthalmic applicator and the second group received sham radiotherapy. Dogs were then monitored for 45 days for recurrent ocular CHV-1 infection using clinical and virological outcome measures. Clinical ophthalmic examinations, ocular sample CHV-1 PCR assays, and serum CHV-1 virus neutralizing antibody assays were performed at specified intervals. No abnormalities suggestive of recurrent CHV-1 ocular disease were observed on clinical examination in any dog during the study. Ocular viral shedding was not detected and CHV-1 virus neutralizing titers remained stable in all dogs. A single fraction 50 Gy radiation dose administered to the ocular surface by strontium-90 beta radiotherapy did not result in detectable recurrent ocular CHV-1 infection in mature dogs with experimentally induced latent infection. Copyright © 2014 Elsevier B.V. All rights reserved.

The enhancement of biological ocular UV radiation on beaches compared to the radiation on grass.

PubMed

Liu, Guang-Cong; Wang, Fang; Gao, Yan-Yan; Yang, Zheng; Hu, Li-Wen; Gao, Qian; Ri, Jun-Chol; Liu, Yang

2014-12-01

The influence of albedo on ocular UV exposure has seldom been reported. This paper aimed to explore the enhancement effect on measured ocular UV radiation due to a sand surface compared to measured ocular UV radiation due to a grass surface. We measured ambient and ocular UV radiation over the beach and grass surface in Sanya City of China (18.4°N, 109.7°E). The experimental apparatus was composed of a manikin and a dual-detector spectrometer. Integration of both UVA and UVB radiation was used to denote UV radiation. Then biologically effective ocular UVB radiation (UVBE) and the ratios of UVBE of two surfaces were calculated. Maximum of ocular UV radiation versus time over the two surfaces is bimodal. UVBE on the beach is significantly larger than UVBE on the sand, and UVBE peaked at different solar elevation angle (SEA) over the two surfaces (about 53° and 40° on the beach and grass, respectively, according to Bayesian regression). The maximum of ocular UVBE ratios is greater than two, which peaked SEA was about 50°. One hour's cumulative radiation under sunny weather exceeds thresholds for photokeratitis, conjunctivitis and lens damage. Higher albedo significantly increased biological ocular UV radiation. Tourists on tropical beaches should take protective measures and avoid facing the sun directly, especially when SEA is around 50°. Copyright © 2014 Elsevier B.V. All rights reserved.

Ocular surface reconstruction with a tissue-engineered nasal mucosal epithelial cell sheet for the treatment of severe ocular surface diseases.

PubMed

Kobayashi, Masakazu; Nakamura, Takahiro; Yasuda, Makoto; Hata, Yuiko; Okura, Shoki; Iwamoto, Miyu; Nagata, Maho; Fullwood, Nigel J; Koizumi, Noriko; Hisa, Yasuo; Kinoshita, Shigeru

2015-01-01

Severe ocular surface diseases (OSDs) with severe dry eye can be devastating and are currently some of the most challenging eye disorders to treat. To investigate the feasibility of using an autologous tissue-engineered cultivated nasal mucosal epithelial cell sheet (CNMES) for ocular surface reconstruction, we developed a novel technique for the culture of nasal mucosal epithelial cells expanded ex vivo from biopsy-derived human nasal mucosal tissues. After the protocol, the CNMESs had 4-5 layers of stratified, well-differentiated cells, and we successfully generated cultured epithelial sheets, including numerous goblet cells. Immunohistochemistry confirmed the presence of keratins 3, 4, and 13; mucins 1, 16, and 5AC; cell junction and basement membrane assembly proteins; and stem/progenitor cell marker p75 in the CNMESs. We then transplanted the CNMESs onto the ocular surfaces of rabbits and confirmed the survival of this tissue, including the goblet cells, up to 2 weeks. The present report describes an attempt to overcome the problems of treating severe OSDs with the most severe dry eye by treating them using tissue-engineered CNMESs to supply functional goblet cells and to stabilize and reconstruct the ocular surface. The present study is a first step toward assessing the use of tissue-engineered goblet-cell transplantation of nonocular surface origin for ocular surface reconstruction. ©AlphaMed Press.

Management of canine corneal squamous cell carcinoma with lamellar keratectomy and strontium 90 plesiotherapy: 3 cases.

PubMed

Nevile, Jessica C; Hurn, Simon D; Turner, Andrew G; McCowan, Christina

2015-05-01

To report three cases of canine corneal squamous cell carcinoma (SCC) treated with strontium 90 beta radiation as an adjunct to surgical excision. Corneal SCC was excised with lamellar keratectomy. This was followed by local application of strontium 90 beta radiation. Available case follow-up times range from 3 to 50 months. One case suffered a recurrence 5 months following initial excision and strontium 90 treatment. Strontium 90 beta radiation has been used extensively as an adjunctive treatment for equine corneal SCC and in other canine ocular tumors; however, there is a paucity of information regarding use in canine corneal SCC. The cases presented here suggest its use following keratectomy may be helpful in preventing disease recurrence. At the dosage used, severe adverse effects were not observed. © 2014 American College of Veterinary Ophthalmologists.

Improvement of chronic corneal opacity in ocular surface disease with prosthetic replacement of the ocular surface ecosystem (PROSE) treatment.

PubMed

Cressey, Anna; Jacobs, Deborah S; Remington, Crystal; Carrasquillo, Karen G

2018-06-01

To demonstrate clearing of chronic corneal opacities and improvement of visual acuity with the use of BostonSight prosthetic replacement of the ocular surface ecosystem (PROSE) treatment in ocular surface disease. We undertook retrospective analysis of the medical records of a series of patients who underwent PROSE treatment from August 2006 to December 2014. Patients were referred for ocular surface disease of various etiologies. Primary inclusion criterion was corneal opacity that improved with PROSE treatment. Patients were excluded if topical steroids or adjuvant therapy used once PROSE treatment was initiated. Underlying disease, prior treatment, clinical presentation, and clinical course were extracted from the medical record. Four patients are included in this series. There were three females and one male; median age at time of treatment initiation was 30 years (range = 0.5-58 years). Median duration of PROSE treatment at time of retrospective analysis was 3.5 years (range = 1-8 years). Two cases had corneal opacification in the context of neurotrophic keratopathy: a unilateral case due to presumed herpes simplex keratitis and a bilateral case due to congenital corneal anesthesia associated with familial dysautonomia. One case had corneal opacity from exposure related to seventh nerve palsy, and one had corneal opacification associated with recurrent surface breakdown, neurotrophic keratopathy, and limbal stem deficiency of uncertain etiology. After consistent wear of prosthetic devices used in PROSE treatment for support of the ocular surface, visual acuity improved and clearing of the opacities was observed, without use of topical steroids or adjuvant therapy. These cases demonstrate clearing of chronic corneal opacity with PROSE treatment for ocular surface disease. This clearing can occur with no adjuvant therapy, suggesting that restoration of ocular surface function and integrity allows for corneal remodeling.

Dry Eye Disease and Microbial Keratitis: Is There a Connection?

PubMed Central

Narayanan, Srihari; Redfern, Rachel L.; Miller, William L.; Nichols, Kelly K.; McDermott, Alison M.

2013-01-01

Dry eye is a common ocular surface disease of multifactorial etiology characterized by elevated tear osmolality and inflammation leading to a disrupted ocular surface. The latter is a risk factor for ocular surface infection, yet overt infection is not commonly seen clinically in the typical dry eye patient. This suggests that important innate mechanisms operate to protect the dry eye from invading pathogens. This article reviews the current literature on epidemiology of ocular surface infection in dry eye patients and laboratory-based studies on innate immune mechanisms operating at the ocular surface and their alterations in human dry eye and animal models. The review highlights current understanding of innate immunity in dry eye and identifies gaps in our knowledge to help direct future studies to further unravel the complexities of dry eye disease and its sequelae. PMID:23583043

Structure and Biological Roles of Mucin-type O-glycans at the Ocular Surface

PubMed Central

Guzman-Aranguez, Ana; Argüeso, Pablo

2010-01-01

Mucins are major components in mucus secretions and apical cell membranes on wet-surfaced epithelia. Structurally, they are characterized by the presence of tandem repeat domains containing heavily O-glycosylated serine and threonine residues. O-glycans contribute to maintaining the highly extended and rigid structure of mucins, conferring to them specific physical and biological properties essential for their protective functions. At the ocular surface epithelia, mucin-type O-glycan chains are short and predominantly sialylated, perhaps reflecting specific requirements of the ocular surface. Traditionally, secreted mucins and their O-glycans in the tear film have been involved in the clearance of debris and pathogens from the surface of the eye. New evidence, however, shows that O-glycans on the cell-surface glycocalyx have additional biological roles in the protection of corneal and conjunctival epithelia, such as preventing bacterial adhesion, promoting boundary lubrication, and maintaining the epithelial barrier function through their interaction with galectin-3. Abnormalities in mucin-type O-glycosylation have been identified in many disorders where the stability of the ocular surface is compromised. This review summarizes recent advances in understanding the structure, biosynthesis, and function of mucin-type O-glycans at the ocular surface and their alteration in ocular surface disease. PMID:20105403

Tear clearance implications for ocular surface health.

PubMed

de Paiva, Cintia Sade; Pflugfelder, Stephen C

2004-03-01

Tear clearance/turnover provides a global assessment of the function of the lacrimal functional unit and of tear exchange on the ocular surface. It is an indirect measure of dry eye induced inflammation on the ocular surface. It shows better correlation with the severity of ocular irritation symptoms and corneal epithelial disease in dry eye than the Schirmer 1 test. Delayed tear clearance may prove to be the best measure for identifying patients with tear film disorders who may respond to anti-inflammatory therapy.

Coal dust contiguity-induced changes in the concentration of TNF- and NF- B p65 on the ocular surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Z.Y.; Hong, J.; Liu, Z.Y.

2009-07-01

To observe the influence of coal dust on ocular surface of coal miners and rabbits with coal dust contiguity on expression TNF- and NF- Bp65 and dry eye occurrence. Expression TNF- and NF- Bp65 in ocular surface were determined. Results showed tear production, BUT and lysozyme decreased for coal miners and rabbits with coal dust contiguity. Coal dust exposure was linked to development of xerophthalmia, and induced a higher expression of NF- B p65 and TNF- perhaps as a mechanism to resist coal dust ocular surface injury.

The Relation of Ocular Surface Irregularity and Visual Disturbance in Early Stage Acanthamoeba Keratitis.

PubMed

Matsumoto, Yukihiro; Kodama, Asako; Goto, Eiki; Kawakita, Tetsuya; Dogru, Murat; Tsubota, Kazuo

2017-01-01

To evaluate the relation between ocular surface irregularity and visual disturbance in early stage Acanthamoeba keratitis (AK). Fifteen patients with culture-proven AK underwent routine ophthalmic examinations, including best-corrected visual acuity (BCVA) measurement, slitlamp biomicroscope examination, and corneal fluorescein dye staining test, in both the eyes. We also evaluated the corneal sensitivity with Cochet-Bonnet esthesiometer, tear functions by Schirmer's test, and ocular surface irregularity by corneal topography and compared the results with the contralateral healthy eyes in this study. The mean logarithm of the minimum angle of resolution BCVA (0.71±0.77) was significantly lower in the eyes with AK (P=0.002). Epithelial disorders were present in all eyes, and radial keratoneuritis in 14 eyes (93.3%). The mean corneal sensitivity (39.3±24.1 mm) was significantly lower in eyes with AK compared with the healthy eyes (P=0.005). The mean Schirmer's test value (22.5±12.0 mm) in eyes with AK was significantly higher compared with the healthy eyes (P=0.01). The ocular surface irregularity indices (the surface regularity index, 2.47±0.42; the surface asymmetry index, 3.24±1.31) were significantly higher in eyes with AK compared with contralateral healthy eyes (P<0.0001 and P<0.0001, respectively). The ocular surface disease in AK is associated with decrease in corneal sensitivity and increase in Schirmer's test value and ocular surface irregularity indices. The visual disturbance in AK may owe not only to corneal haze but also to ocular surface irregularity.

JBP485 promotes tear and mucin secretion in ocular surface epithelia

PubMed Central

Nakamura, Takahiro; Hata, Yuiko; Nagata, Maho; Yokoi, Norihiko; Yamaguchi, Shumpei; Kaku, Taiichi; Kinoshita, Shigeru

2015-01-01

Dry eye syndrome (DES), a multifactorial disease of the tears and ocular surface, is one of the most common ocular disorders. Tear film contains ocular mucins and is essential for maintaining the homeostasis of the wet ocular surface. Since there are a limited number of clinical options for the treatment of DES, additional novel treatments are needed to improve the clinical results. In this study, we found that placental extract-derived dipeptide (JBP485) clearly promoted the expression and secretion of gel-forming mucin 5ac (Muc5ac) in rabbit conjunctival epithelium. JBP485 also elevated the expression level of cell surface-associated mucins (Muc1/4/16) in rabbit corneal epithelium. The Schirmer tear test results indicated that JBP485 induced tear secretion in the rabbit model. Moreover, JBP485 clinically improved corneal epithelial damage in a mouse dry eye model. Thus, our data indicate that JBP485 efficiently promoted mucin and aqueous tear secretion in rabbit ocular surface epithelium and has the potential to be used as a novel treatment for DES. PMID:25996902

JBP485 promotes tear and mucin secretion in ocular surface epithelia.

PubMed

Nakamura, Takahiro; Hata, Yuiko; Nagata, Maho; Yokoi, Norihiko; Yamaguchi, Shumpei; Kaku, Taiichi; Kinoshita, Shigeru

2015-05-21

Dry eye syndrome (DES), a multifactorial disease of the tears and ocular surface, is one of the most common ocular disorders. Tear film contains ocular mucins and is essential for maintaining the homeostasis of the wet ocular surface. Since there are a limited number of clinical options for the treatment of DES, additional novel treatments are needed to improve the clinical results. In this study, we found that placental extract-derived dipeptide (JBP485) clearly promoted the expression and secretion of gel-forming mucin 5ac (Muc5ac) in rabbit conjunctival epithelium. JBP485 also elevated the expression level of cell surface-associated mucins (Muc1/4/16) in rabbit corneal epithelium. The Schirmer tear test results indicated that JBP485 induced tear secretion in the rabbit model. Moreover, JBP485 clinically improved corneal epithelial damage in a mouse dry eye model. Thus, our data indicate that JBP485 efficiently promoted mucin and aqueous tear secretion in rabbit ocular surface epithelium and has the potential to be used as a novel treatment for DES.

Ocular manifestations of xeroderma pigmentosum: long term follow-up highlights the role of DNA repair in protection from sun damage

PubMed Central

Brooks, Brian P; Thompson, Amy H; Bishop, Rachel J; Clayton, Janine A; Chan, Chi-Chao; Tsilou, Ekaterini T; Zein, Wadih M; Tamura, Deborah; Khan, Sikandar G.; Ueda, Takahiro; Boyle, Jennifer; Oh, Kyu-Seon; Imoto, Kyoko; Inui, Hiroki; Moriwaki, Shin-Ichi; Emmert, Steffen; Iliff, Nicholas T.; Bradford, Porcia; DiGiovanna, John J.; Kraemer, Kenneth H

2013-01-01

Objective Xeroderma pigmentosum (XP) is a rare autosomal recessive disease caused by mutations in DNA repair genes. Clinical manifestations of XP include mild to extreme sensitivity to ultraviolet radiation resulting in inflammation and neoplasia in sun-exposed areas of the skin, mucous membranes, and ocular surfaces. This report describes the ocular manifestations of XP in patients systematically evaluated in the Clinical Center at the National Institutes of Health. Design Retrospective Observational Case Series Participants Eighty-seven participants, aged 1.3 to 63.4 years, referred to the National Eye Institute for examination from 1964 to 2011. Eighty-three had XP, 3 had XP/Cockayne Syndrome complex, and 1 had XP/trichothiodystrophy complex. Methods Complete, age- and developmental stage-appropriate ophthalmic examination. Main Outcome Measures Visual acuity; eyelid, ocular surface and lens pathology; tear film and tear production measures; and cytological analysis of conjunctival surface swabs. Results Of the 87 patients, 91% had at least one ocular abnormality. The most common abnormalities were conjunctivitis (51%), corneal neovascularization (44%), dry eye (38%), corneal scarring (26%), ectropion (25%), blepharitis (23%), conjunctival melanosis (20%), and cataracts (14%). Thirteen percent of patients had some degree of visual axis impingement and 5% had no light perception in one or both eyes. Ocular surface cancer or a history of ocular surface cancer was present in 10% of patients. Patients with an acute sunburning skin phenotype were less likely to develop conjunctival melanosis and ectropion but more likely to develop neoplastic ocular surface lesions than non-burning patients. Some patients also showed signs of limbal stem cell deficiency. Conclusions Our longitudinal study reports the ocular status of the largest group of XP patients systematically examined at one facility over an extended period of time. Structural eyelid abnormalities, neoplasms of the ocular surface and eyelids, tear film and tear production abnormalities, ocular surface disease and inflammation, as well as corneal abnormalities were present in this population. Burning and non-burning XP patients exhibit different rates of important ophthalmologic findings, including neoplasia. Additionally, ophthalmic characteristics can help refine diagnoses in the case of XP complex phenotypes. DNA repair plays major role in protection of the eye from sunlight induced damage. PMID:23601806

The surface activity of purified ocular mucin at the air-liquid interface and interactions with meibomian lipids.

PubMed

Millar, Thomas J; Tragoulias, Sophia T; Anderton, Philip J; Ball, Malcolm S; Miano, Fausto; Dennis, Gary R; Mudgil, Poonam

2006-01-01

Ocular mucins are thought to contribute to the stability of the tear film by reducing surface tension. The purpose of this study was to compare the effect of different mucins and hyaluronic acid (HA) alone and mixed with meibomian lipids on the surface pressure at an air-liquid interface. A Langmuir trough and Wilhelmy balance were used to measure and compare the surface activity of bovine submaxillary gland mucin (BSM), purified BSM, purified bovine ocular mucin and HA, and mixtures of these with meibomian lipids, phosphatidylcholine, and phosphatidylglycerol. Their appearance at the surface of an air-buffer interface was examined using epifluorescence microscopy. Purified ocular mucin had no surface activity even at concentrations that were 100 times more than normally occur in tears. By contrast, commercial BSM caused changes to surface pressure that were concentration dependent. The surface pressure-area profiles showed surface activity with maximum surface pressures of 12.3-22.5 mN/m depending on the concentration. Purified BSM showed no surface activity at low concentrations, whereas higher concentrations reached a maximum surface pressure of 25 mN/m. HA showed no surface activity, at low or high concentrations. Epifluorescence showed that the mucins were located at the air-buffer interface and changed the appearance of lipid films. Purified bovine ocular mucin and HA have no surface activity. However, despite having no surface activity in their own right, ocular mucins are likely to be present at the surface of the tear film, where they cause an increase in surface pressure by causing a compression of the lipids (a reorganization of the lipids) and alter the viscoelastic properties at the surface.

Rehabilitation of orbital cavity after orbital exenteration using polymethyl methacrylate orbital prosthesis.

PubMed

Jain, Sumeet; Jain, Parul

2016-01-01

Squamous cell carcinoma of the eyelid is the second most common malignant neoplasm of the eye with the incidence of 0.09 and 2.42 cases/100 000 people. Orbital invasion is a rare complication but, if recognized early, can be treated effectively with exenteration. Although with advancements in technology such as computer-aided design and computer-aided manufacturing, material science, and retentive methods like implants, orbital prosthesis with stock ocular prosthesis made of methyl methacrylate retained by anatomic undercuts is quiet effective and should not be overlooked and forgotten. This clinical report describes prosthetic rehabilitation of two male patients with polymethyl methacrylate resin orbital prosthesis after orbital exenteration, for squamous cell carcinoma of the upper eyelid. The orbital prosthesis was sufficiently retained by hard and soft tissue undercuts without any complications. The patients using the prosthesis are quite satisfied with the cosmetic results and felt comfortable attending the social events.

Targeted delivery of hyaluronic acid to the ocular surface by a polymer-peptide conjugate system for dry eye disease.

PubMed

Lee, David; Lu, Qiaozhi; Sommerfeld, Sven D; Chan, Amanda; Menon, Nikhil G; Schmidt, Tannin A; Elisseeff, Jennifer H; Singh, Anirudha

2017-06-01

Hyaluronic acid (HA) solutions effectively lubricate the ocular surface and are used for the relief of dry eye related symptoms. However, HA undergoes rapid clearance due to limited adhesion, which necessitates frequent instillation. Conversely, highly viscous artificial tear formulations with HA blur vision and interfere with blinking. Here, we developed an HA-eye drop formulation that selectively binds and retains HA for extended periods of time on the ocular surface. We synthesized a heterobifunctional polymer-peptide system with one end binding HA while the other end binding either sialic acid-containing glycosylated transmembrane molecules on the ocular surface epithelium, or type I collagen molecule within the tissue matrix. HA solution was mixed with the polymer-peptide system and tested on both ex vivo and in vivo models to determine its ability to prolong HA retention. Furthermore, rabbit ocular surface tissues treated with binding peptides and HA solutions demonstrated superior lubrication with reduced kinetic friction coefficients compared to tissues treated with conventional HA solution. The results suggest that binding peptide-based solution can keep the ocular surface enriched with HA for prolonged times as well as keep it lubricated. Therefore, this system can be further developed into a more effective treatment for dry eye patients than a standard HA eye drop. Eye drop formulations containing HA are widely used to lubricate the ocular surface and relieve dry eye related symptoms, however its low residence time remains a challenge. We designed a polymer-peptide system for the targeted delivery of HA to the ocular surface using sialic acid or type I collagen as anchors for HA immobilization. The addition of the polymer-peptide system to HA eye drop exhibited a reduced friction coefficient, and it can keep the ocular surface enriched with HA for prolonged time. This system can be further developed into a more effective treatment for dry eye than a standard HA eye drop. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Aniridia and Brachmann-de Lange syndrome: a review of ocular surface and anterior segment findings.

PubMed

Lee, W Barry; Brandt, James D; Mannis, Mark J; Huang, Charles Q; Rabin, Gregory J

2003-03-01

To review the ocular surface and anterior segment findings in Brachmann-de Lange syndrome and describe a new case involving aniridia and congenital glaucoma. A newborn presented 2 days after birth with bilateral cloudy corneas, photophobia, and epiphora. We provide a 5-year descriptive history and clinical course with review of the literature on Brachmann-de Lange syndrome. Multiple ocular surgeries were performed for ocular sequelae from aniridia and congenital glaucoma including Ahmed valve placement and penetrating keratoplasties in both eyes. At 5.5 years of age, the child had a clear graft OD and amblyopia from graft failure OS following recurrent graft infections. A review of Brachmann-de Lange syndrome found 43 patients with ocular surface and anterior segment findings. The most common findings included conjunctivitis, blepharitis, microcornea, and corectopia. Aniridia and congenital glaucoma were not previously reported with Brachmann-de Lange syndrome. Ocular surface and anterior segment abnormalities must be considered when examining patients with Brachmann-de Lange syndrome. Ocular findings may include vision-threatening anomalies, as in our case with aniridia and congenital glaucoma. To our knowledge, these findings are previously unreported in Brachmann-de Lange syndrome.

Dry eye disease: an immune-mediated ocular surface disorder

PubMed Central

Stevenson, William; Chauhan, Sunil K.; Dana, Reza

2013-01-01

Dry eye disease is a multifactorial disorder of the tears and ocular surface characterized by symptoms of dryness and irritation. Although the pathogenesis of dry eye disease is not fully understood, it is recognized that inflammation has a prominent role in the development and propagation of this debilitating condition. Factors that adversely affect tear film stability and osmolarity can induce ocular surface damage and initiate an inflammatory cascade that generates innate and adaptive immune responses. These immunoinflammatory responses lead to further ocular surface damage and the development of a self-perpetuating inflammatory cycle. Herein, we review the fundamental links between inflammation and dry eye disease and discuss the clinical implications of inflammation in disease management. PMID:22232476

Accounting for Ethnicity-Related Differences in Ocular Surface Integrity as a Step Toward Understanding Contact Lens Discomfort.

PubMed

Chan, Stefanie M; Svitova, Tatyana F; Lin, Meng C

2017-01-01

Contact lens discomfort is a common problem that can lead to unsuccessful or limited contact lens wear. Although many factors may contribute to contact lens discomfort, limited research has explored the influence of ethnicity-related differences in the anatomy and physiology of the ocular surface. Therefore, we performed a search of the literature in PubMed using key words related to "ocular surface" paired with the terms "race" and "ethnicity." The goal of this review was to determine potential areas of research regarding ethnicity differences, particularly between Asian and non-Asian eyes, in ocular surface integrity to advance our understanding of contact lens discomfort.

SFTA3 - a novel surfactant protein of the ocular surface and its role in corneal wound healing and tear film surface tension.

PubMed

Schicht, Martin; Garreis, Fabian; Hartjen, Nadine; Beileke, Stephanie; Jacobi, Christina; Sahin, Afsun; Holland, Detlef; Schröder, Henrik; Hammer, Christian M; Paulsen, Friedrich; Bräuer, Lars

2018-06-28

The study aimed to characterize the expression and function of SFTA3 at the ocular surface and in tears. Ocular tissues, conjunctival (HCjE) and human corneal (HCE) epithelial cell lines as well as tearfilm of patients suffering from different forms of dry eye disease (DED) were analyzed by means of RT-PCR, western blot, immunohistochemistry, and ELISA. A possible role of recombinant SFTA3 in corneal wound healing was investigated performing in vitro scratch assays. Tear film regulatory properties were analyzed with the spinning drop method and the regulation of SFTA3 transcripts was studied in HCE and HCjE after incubation with proinflammatory cytokines as well as typical ocular pathogens by real-time RT-PCR and ELISA. The results reveal that human ocular tissue as well as tears of healthy volunteers express SFTA3 whereas tears from patients with DED showed significantly increased SFTA3 levels. In vitro wounding of HCE cell cultures that had been treated with recombinant SFTA3 demonstrated a significantly increased wound closure rate and rSFTA3 reduced the surface tension of tear fluid. The results indicate that SFTA3 at the ocular surface seemed to be involved in wound healing and the reduction of surface tension.

Interfacial Interaction between Transmembrane Ocular Mucins and Adhesive Polymers and Dendrimers Analyzed by Surface Plasmon Resonance

PubMed Central

Noiray, M.; Briand, E.; Woodward, A. M.; Argüeso, P.; Molina Martínez, I. T.; Herrero-Vanrell, R.; Ponchel, G.

2013-01-01

Purpose Development of the first in vitro method based on biosensor chip technology designed for probing the interfacial interaction phenomena between transmembrane ocular mucins and adhesive polymers and dendrimers intended for ophthalmic administration. Methods The surface plasmon resonance (SPR) technique was used. A transmembrane ocular mucin surface was prepared on the chip surface and characterized by QCM-D (Quartz Crystal Microbalance with Dissipation) and XPS (X-ray photoelectron spectroscopy). The mucoadhesive molecules tested were: hyaluronic acid (HA), carboxymethyl cellulose (CMC), hydroxypropylmethyl cellulose (HPMC), chitosan (Ch) and polyamidoamine dendrimers (PAMAM). Results While Ch originated interfacial interaction with ocular transmembrane mucins, for HA, CMC and HPMC, chain interdiffusion seemed to be mandatory for bioadherence at the concentrations used in ophthalmic clinical practise. Interestingly, PAMAM dendrimers developed permanent interfacial interactions with transmembrane ocular mucins whatever their surface chemical groups, showing a relevant importance of co-operative effect of these multivalent systems. Polymers developed interfacial interactions with ocular membrane-associated mucins in the following order: Ch(1 %) > G4PAMAM-NH2(2 %) = G4PAMAM-OH(2 %) > G3.5PAMAM-COOH(2 %)≫ CMC(0.5 %) = HA(0.2 %) = HPMC(0.3 %). Conclusions The method proposed is useful to discern between the mucin-polymer chemical interactions at molecular scale. Results reinforce the usefulness of chitosan and den-drimers as polymers able to increase the retention time of drugs on the ocular surface and hence their bioavailability. PMID:22565639

Ophthalmic Manifestations of Xeroderma Pigmentosum: A Perspective from the United Kingdom.

PubMed

Lim, Rongxuan; Sethi, Mieran; Morley, Ana M S

2017-11-01

To document the ocular manifestations of xeroderma pigmentosum (XP), presenting via the United Kingdom (UK) XP service, and to analyze the correlations between XP genotype and ophthalmic phenotype. Prospective observational case series. Eighty-nine patients seen by the UK Nationally Commissioned XP Service, from April 2010 to December 2014, with a genetically confirmed diagnosis of XP. Patients underwent a full ophthalmic examination at each visit. Clinical features from both eyes were recorded on a standard proforma. The most recent assessments were analyzed. A 2-tailed Fisher exact test was used to assess for differences in ocular features between patients in XP subgroups with impaired transcription coupled nucleotide excision repair (TC-NER) (category 1: XP-A, B, D, F, and G) and preserved TC-NER (category 2: XP-C, E, and V). Lid and periocular abnormalities, ocular surface pathologies, neuro-ophthalmologic abnormalities, lens and retinal abnormalities, and visual acuity (VA). Ninety-three percent of XP patients in our cohort had ocular involvement, with 65% describing photophobia. The most common abnormalities were in the periocular skin and ocular surface, including interpalpebral conjunctival melanosis (44%) and conjunctival injection (43%). Eleven percent of patients had required treatment for periocular cancers and 2% for ocular surface cancers. The most common neuro-ophthalmologic finding was minimal pupillary reaction to light (25%). Patients in category 2 had significantly more ocular surface abnormalities than patients in category 1, including a greater proportion of conjunctival injection (P = 0.003), conjunctival corkscrew vessels (P < 0.001), corneal scarring (P = 0.01) and pingueculae under the age of 50 (P = 0.02). Meanwhile, patients in category 1 had a higher proportion of poorly reactive pupils (P < 0.001) and abnormal ocular movements (P = 0.03) compared with those in category 2. Five patients (6%) presented to ophthalmologists with ocular surface signs related to XP, before any formal diagnosis of XP was made. A large proportion of XP patients have ocular involvement. Regular examination by an ophthalmologist is essential, especially in screening for eyelid and ocular surface tumors. The ocular phenotype-genotype segregation within XP patients suggests that XP is a heterogeneous and complex disease. With further study, we hope to offer these patients more individualized patient care. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

The ocular surface and tear film and their dysfunction in dry eye disease.

PubMed

Rolando, M; Zierhut, M

2001-03-01

The ocular surface, tear film, lacrimal glands, and eyelids act as a functional unit to preserve the quality of the refractive surface of the eye and to resist injury and protect the eye against changing bodily and environmental conditions. Events that disturb the homeostasis of this functional unit can result in a vicious cycle of ocular surface disease. The tear film is the most dynamic structure of the functional unit, and its production and turnover is essential to maintaining the health of the ocular surface. Classically, the tear film is reported to be composed of three layers: the mucin, aqueous, and lipid layers. The boundaries and real thickness of such layers is still under discussion. A dysfunction of any of these layers can result in dry eye disease.

Vitamin A Deficiency Due to Selective Eating as a Cause of Blindness in a High-Income Setting.

PubMed

Martini, Silvia; Rizzello, Angela; Corsini, Ilaria; Romanin, Benedetta; Fiorentino, Michelangelo; Grandi, Sara; Bergamaschi, Rosalba

2018-04-01

Vitamin A is a fat-soluble micronutrient involved in the regulation of several physiologic functions, such as visual acuity, epithelial tissue integrity, immune response, and gene expression, thus playing a crucial role in childhood growth and development. Although vitamin A deficiency (VAD) in resource-limited settings is still an actual issue and represents the leading cause of preventable childhood blindness, its occurrence in high-income countries is rare, although possibly underdiagnosed because of its nonspecific early manifestations. A good awareness of VAD symptoms and risk factors could aid its early diagnosis, which is fundamental to undertake a prompt treatment and to prevent ocular complications. Nevertheless, the role of restrictive dietary habits, increasingly common in developed countries, is often overlooked in infants and children. We present a case of VAD with permanent ocular sequelae in a 5-year-old girl from a high-income country. In the case described, VAD ensued from a highly restricted diet, mainly limited to oat milk, which had been followed for more than 2 years. This child presented with ocular symptoms, opportunistic infection, anemia, poor growth, and a diffuse squamous metaplasia of the bladder; after commencing retinol supplementation, a gradual healing of clinical VAD manifestations occurred, with the exception of the ocular sequelae, which resulted in irreversible visual loss. Copyright © 2018 by the American Academy of Pediatrics.

Therapeutic Effects of Sodium Hyaluronate on Ocular Surface Damage Induced by Benzalkonium Chloride Preserved Anti-glaucoma Medications

PubMed Central

Liu, Xing; Yu, Fen-Fen; Zhong, Yi-Min; Guo, Xin-Xing; Mao, Zhen

2015-01-01

Background: Long-term use of benzalkonium chloride (BAC)-preserved drugs is often associated with ocular surface toxicity. Ocular surface symptoms had a substantial impact on the glaucoma patients’ quality of life and compliance. This study aimed to investigate the effects of sodium hyaluronate (SH) on ocular surface toxicity induced by BAC-preserved anti-glaucoma medications treatment. Methods: Fifty-eight patients (101 eyes), who received topical BAC-preserved anti-glaucoma medications treatment and met the severe dry eye criteria, were included in the analysis. All patients were maintained the original topical anti-glaucoma treatment. In the SH-treated group (56 eyes), unpreserved 0.3% SH eye drops were administered with 3 times daily for 90 days. In the control group (55 eyes), phosphate-buffered saline were administered with 3 times daily for 90 days. Ocular Surface Disease Index (OSDI) questionnaire, break-up time (BUT) test, corneal fluorescein staining, corneal and conjunctival rose Bengal staining, Schirmer test, and conjunctiva impression cytology were performed sequentially on days 0 and 91. Results: Compared with the control group, SH-treated group showed decrease in OSDI scores (Kruskal-Wallis test: H = 38.668, P < 0.001), fluorescein and rose Bengal scores (Wilcoxon signed-ranks test: z = −3.843, P < 0.001, and z = −3.508, P < 0.001, respectively), increase in tear film BUT (t-test: t = −10.994, P < 0.001) and aqueous tear production (t-test: t = −10.328, P < 0.001) on day 91. The goblet cell density was increased (t-test: t = −9.981, P < 0.001), and the morphology of the conjunctival epithelium were also improved after SH treatment. Conclusions: SH significantly improved both symptoms and signs of ocular surface damage in patients with BAC-preserved anti-glaucoma medications treatment. SH could be proposed as a new attempt to reduce ocular surface toxicity, and alleviate symptoms of ocular surface damage in BAC-preserved anti-glaucoma medications treatment. PMID:26365960

The treatment of carcinoma in situ and squamous cell carcinoma of the conjunctiva with fractionated strontium-90 radiation in a population with a high prevalence of HIV.

PubMed

Lecuona, Karin; Stannard, Clare; Hart, Gregory; Rice, James; Cook, Colin; Wetter, Julie; Duffield, Maureen

2015-09-01

This study explores the safety and efficacy of strontium 90 (Sr-90) brachytherapy as the sole adjuvant therapy for carcinoma in situ (CIS) and squamous cell carcinoma (SCC) of the conjunctiva in a high HIV prevalent area. This is a retrospective case review of patients treated with 60 Gray Sr-90 brachytherapy in four divided doses after resection with a 2 mm margin and histological confirmation. Cryotherapy or alcohol debridement was not performed at the time of excision due to limited resources. Two plaque sizes, 8.5 mm and 18 mm, were used. Sixty-nine patients were treated and had a median follow-up of 27 months (range 6-127). Thirty-three (47.8%) were HIV-positive. CIS was present in 40.6% and SCC in 59.4%. The surgical margins were positive in 39 (56.5%). Twenty patients (29.0%) were treated with the 18 mm plaque and 49 (71.0%) with the 8.5 mm plaque. Eight (11.6%) patients developed a recurrence at a median of 5 months (range 2-40). Recurrences only occurred in patients treated with the 8.5 mm plaque (p=0.094). There was no significant effect of HIV status, positive margins or staging on the number of recurrences. Treatment side effects were a dry eye in five patients which was successfully managed with topical lubricants, and induced astigmatism of 1 dioptre of cylinder in one patient. Sr-90 brachytherapy is safe and effective in preventing recurrences in ocular surface squamous neoplasia in a high HIV prevalent setting. The 18 mm plaque size is superior to the 8.5 mm plaque size. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Protecting the ocular surface and improving the quality of life of dry eye patients: a study of the efficacy of an HP-guar containing ocular lubricant in a population of dry eye patients.

PubMed

Rolando, Maurizio; Autori, Silvia; Badino, Francesco; Barabino, Stefano

2009-06-01

The aim of this study was to evaluate the efficacy of a non-Newtonian tear substitute containing 0.4% polyethylene glycol 400 (PEG 400) and 0.3% propylene glycol in an 0.18% hydroxypropyl-guar (HPG) containing vehicle (Systane Lubricant Eye Drops; Alcon) in reducing the signs and symptoms of dry eye, as well as its effect on ocular protection. Twenty patients with moderate to severe dry eye were enrolled in a 28-day prospective, randomized, controlled study. Subjects self-administered the HPG containing ocular lubricant four times daily (QID) over the study duration. After 28 days, the effect of the HPG containing ocular lubricant was evaluated by means of the Global Staining Score (a measure of the corneal and conjunctival staining), inter-blink tear film stability, Ocular Protection Index (OPI), and subjective symptoms. The HPG containing ocular lubricant produced statistically significant improvements compared with baseline in dry eye symptoms (P < 0.0001 at Days 7, 14, and 28); in ocular surface staining, as measured by a reduction in the Global Staining Score (P < 0.0001 at Days 7, 14, and 28); and in the OPI (P = 0.0025 at Day 14 and P = 0.0067 at Day 28). The improvements in ocular surface staining and dry eye symptoms with the HPG containing ocular lubricant -- evident as early as the first follow-up visit (Day 7) and continued throughout the 28 days of the study with a concurrent, increase in OPI to a level greater than unity -- indicate that this preparation is a fast-acting, long-lasting, and effective treatment for dry eye. In concurrence with the results from previously published clinical studies, the HPG containing ocular lubricant has shown efficacy in alleviating the signs and symptoms of dry eye as well as affording improved ocular surface protection.

The Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis).

PubMed

Galor, Anat; Small, Leslie; Feuer, William; Levitt, Roy C; Sarantopoulos, Konstantinos D; Yosipovitch, Gil

2017-08-01

To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Analyses were performed to examine for differences between those with and without subjective complaints of ocular itch. The mean age was 62 years with 92% being male. Symptoms of DE and NOP were more frequent in patients with moderate-severe ocular itch compared to those with no or mild ocular itch symptoms. With the exception of ocular surface inflammation (abnormal matrix metalloproteinase 9 testing) which was less common in those with moderate-severe ocular itch symptoms, DE signs were not related to ocular itch. Individuals with moderate-severe ocular itch also demonstrated greater sensitivity to evoked pain on the forearm and had higher non-ocular pain, depression, and post-traumatic stress disorders scores, compared to those with no or mild itch symptoms. Subjects with moderate-severe ocular itch symptoms have more severe symptoms of DE, NOP, non-ocular pain and demonstrate abnormal somatosensory testing in the form of increased sensitivity to evoked pain at a site remote from the eye, consistent with generalized hypersensitivity.

The Relationship Between Ocular Itch, Ocular Pain, and Dry Eye Symptoms (An American Ophthalmological Society Thesis)

PubMed Central

Galor, Anat; Small, Leslie; Feuer, William; Levitt, Roy C.; Sarantopoulos, Konstantinos D.; Yosipovitch, Gil

2017-01-01

Purpose To evaluate associations between sensations of ocular itch and dry eye (DE) symptoms, including ocular pain, and DE signs. Methods A cross-sectional study of 324 patients seen in the Miami Veterans Affairs eye clinic was performed. The evaluation consisted of questionnaires regarding ocular itch, DE symptoms, descriptors of neuropathic-like ocular pain (NOP), and evoked pain sensitivity testing on the forehead and forearm, followed by a comprehensive ocular surface examination including corneal mechanical sensitivity testing. Analyses were performed to examine for differences between those with and without subjective complaints of ocular itch. Results The mean age was 62 years with 92% being male. Symptoms of DE and NOP were more frequent in patients with moderate-severe ocular itch compared to those with no or mild ocular itch symptoms. With the exception of ocular surface inflammation (abnormal matrix metalloproteinase 9 testing) which was less common in those with moderate-severe ocular itch symptoms, DE signs were not related to ocular itch. Individuals with moderate-severe ocular itch also demonstrated greater sensitivity to evoked pain on the forearm and had higher non-ocular pain, depression, and post-traumatic stress disorders scores, compared to those with no or mild itch symptoms. Conclusions Subjects with moderate-severe ocular itch symptoms have more severe symptoms of DE, NOP, non-ocular pain and demonstrate abnormal somatosensory testing in the form of increased sensitivity to evoked pain at a site remote from the eye, consistent with generalized hypersensitivity. PMID:29391860

Adjunctive radiotherapy with strontium-90 in the treatment of conjunctival squamous cell carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kearsley, J.H.; Fitchew, R.S.; Taylor, R.G.

1988-03-01

Squamous cell carcinoma of the ocular conjunctiva is a relatively rare malignancy which is attended by a high rate of local recurrence following simple surgical excision. To date, the management of conjunctival squamous cell cancer has been controversial. From 1950 to 1985, 146 consecutive patients with superficial conjunctival squamous cell cancer were treated at the Queensland Radium Institute. All patients were treated by simple surgical excision of the visible conjunctival lesion followed by adjunctive radiotherapy. Of 140 patients with histologically confirmed squamous cell cancer, 123 were treated with a strontium-90 source, 10 with a radon ring, and 7 with superficialmore » X ray therapy. Standard policy since 1960 has been to deliver an incident dose of 30 Gy in a single fraction within the first 48 post-operative hours to the surgical bed using a strontium-90 source on a stand-off eye applicator. This report will largely focus on the 123 patients who were treated with a strontium-90 source, of whom 107 received 30 Gy, 14 received 40 Gy (pre 1960) and one patient each received 20 and 25 Gy incident dose. Of 131 evaluable patients, there were only 3 who developed local recurrence. All 3 local recurrences developed in elderly men who had presented with extensive superficial primary tumors. Two of the three recurrences occurred in the two patients who were treated with doses less than 30 Gy. Both early and late radiation-induced complications following ablative surgery and treatment with strontium-90 were very uncommon. Three patients developed unsightly conjunctival telangiectasia, 2 patients developed a persistent scleral ulcer and 2 patients developed clinically significant cataracts.« less

Two Patients with Dry Eye Disease Followed Up Using an Expression Assay of Ocular Surface Mucin.

PubMed

Machida, Yumiko; Shoji, Jun; Harada, Natsuko; Inada, Noriko

2016-01-01

We report 2 patients with dry eye disease followed up using the expression levels of ocular surface mucin. Patient 1: a 57-year-old woman with Sjögren's syndrome-associated dry eyes experienced severe dryness and foreign body sensation in both her eyes, and instilled sodium hyaluronate ophthalmic solution 0.3% about 10-15 times daily. We measured the expression levels of MUC5AC mRNA (MUC5AC) and MUC16 mRNA (MUC16) by using real-time reversed transcription polymerase chain reaction for the specimens of modified impression cytology. Expression levels of MUC5AC and MUC16 on her ocular surface were very low. Subjective symptoms and expression levels of ocular surface mucin improved after combined treatment of rebamipide (4 times daily) and fluorometholone (once daily) ophthalmic suspension. Patient 2: a 62-year-old man with chronic graft-versus-host disease-associated dry eye experienced severe foreign body sensation and developed superficial punctate keratopathy with mucous thread and filamentary keratitis. Expression level of MUC5AC was very high at baseline. Subjective symptoms and expression levels of ocular surface mucin improved by combined treatment of rebamipide (4 times daily) and fluorometholone (once daily) ophthalmic suspension. Clinical test for MUC gene expression on the ocular surface was found to be useful in the follow-up of dry eye treatment.

Transnasal endoscopic approach with powered instrumentation for treating squamous papilloma in the nasopharyngeal surface of the soft palate.

PubMed

Lee, J-H; Lee, Y-O; Lee, C-H; Cho, K-S

2013-05-01

To demonstrate a safe and effective method for complete resection of squamous papilloma in the nasopharyngeal surface of the soft palate. This technique was used on a patient in whom the papilloma had twice recurred following uvulopalatopharyngoplasty. Case report and review of the relevant literature. The patient reported in this paper had recurrent squamous papilloma in the nasopharyngeal surface of the soft palate following uvulopalatopharyngoplasty. He also suffered from nasal regurgitation when drinking water. This lesion, which was difficult to access, was successfully treated via a transnasal endoscopic approach using powered instrumentation. This case report highlights a novel approach for the complete removal of a recurrent papilloma in a relatively inaccessible location. Compared with a transoral approach such as uvulopalatopharyngoplasty, the transnasal endoscopic approach using powered instrumentation could provide a safer, faster, easier and less invasive means of treating squamous papilloma in the nasopharyngeal surface of the soft palate, especially for a lesion that recurs following a transoral approach.

Development of a second-generation novel UVR sensor for the quantification of the light field at the anterior ocular surface

NASA Astrophysics Data System (ADS)

Fleming, David; Walsh, James E.; Moore, Linda; Bergmanson, Jan P. G.; McMahon, David

2005-06-01

Research has shown in recent years that acute and cumulative exposure to excessive ultraviolet radiation (UVR) can cause a range of degenerative ocular conditions such as pterygium, photokeratitis and pinguecula. The increase in natural solar UVR as a result of the depletion of the ozone layer has led to a greater awareness of the adverse effects of UVR on the anterior ocular surface tissues. The relevance of this lies in the fact that these tissues are not immune to photodamage and that there is selective absorption of UVR by conjunctival and corneal tissue in the anterior ocular surface. Therefore, there is a demand for more precise quantification and localisation of UVR incidence at the anterior ocular surface. A novel solar blind photodiode sensor array has been designed, constructed and tested for this purpose. The emphasis of the measurements made by this sensor system is the acquisition of real time, field based surveys of the ocular UVR light field in a broad range of insolation environments. These data will then provide a thorough database of UVR irradiances that can be related to induced damage of anterior ocular tissue. Results to date show the first measured, in-vivo, absolute UVR levels on the eye, the corresponding relative field across the eye and the presence of nasal-temporal biases that exist.

Limitations of an ocular surface inflammatory biomarker in impression cytology specimens.

PubMed

Yafawi, Rolla; Ko, Mira; Sace, Frederick P; John-Baptiste, Annette

2013-03-01

A number of ocular conditions, such as dry eye, are associated with inflammation on the surface of the eye leading to irritation and ocular pain. Many drugs such as chemotherapeutics, beta blockers, angiotensin-converting enzymes and so forth also cause dry eye but currently there are no validated ocular surface biomarkers available. We evaluated sample stability, assay sensitivity, reproducibility and overall performance of impression cytology (IC) utilizing the cellular surface biomarker human leukocyte antigen DR-1 (HLA-DR) as an ocular surface inflammatory biomarker by flow cytometry in a fit-for-purpose validation study. Additionally, subjects classified as normal or having various degrees of dry eye were evaluated to determine if HLA-DR could demonstrate a clear separation between normal and dry eye samples. The assay demonstrated high dynamic range detecting a broad range of fluorescent intensities in healthy donors. Additionally, inter, intra and stability assay results demonstrated strong concordance and low variability. Overall CV% for both assays were less than 25% for all measured parameters. However, high variability was observed for donor samples assayed beyond day 10 post IC sample collection (4.2-110.8 CV%). HLA-DR expression demonstrated a progressive increase in patients with mild to severe levels of dry eye disease providing sufficient evidence it is sensitive enough to monitor inflammatory effects of dry eye when coupled with additional biomarkers and/or methodologies such as cytokine analysis or ICAM-1. This biomarker can be used to monitor ocular surface disorders in patients and to evaluate potential treatment options during drug development. Although our results demonstrate this methodology is reproducible for routine evaluation, limitations around sample integrity exist. The ocular cell surface inflammatory biomarker, HLA-DR coupled with impression cytology is a simple non-invasive robust, specific and reproducible assay that can be utilized to measure inflammatory infiltrates on the surface of the eye in IC samples less than 10-days old.

Modeling of mouse eye and errors in ocular parameters affecting refractive state

NASA Astrophysics Data System (ADS)

Bawa, Gurinder

Rodents eye are particularly used to study refractive error state of an eye and development of refractive eye. Genetic organization of rodents is similar to that of humans, which makes them interesting candidates to be researched upon. From rodents family mice models are encouraged over rats because of availability of genetically engineered models. Despite of extensive work that has been performed on mice and rat models, still no one is able to quantify an optical model, due to variability in the reported ocular parameters. In this Dissertation, we have extracted ocular parameters and generated schematics of eye from the raw data from School of Medicine, Detroit. In order to see how the rays would travel through an eye and the defects associated with an eye; ray tracing has been performed using ocular parameters. Finally we have systematically evaluated the contribution of various ocular parameters, such as radii of curvature of ocular surfaces, thicknesses of ocular components, and refractive indices of ocular refractive media, using variational analysis and a computational model of the rodent eye. Variational analysis revealed that variation in all the ocular parameters does affect the refractive status of the eye, but depending upon the magnitude of the impact those parameters are listed as critical or non critical. Variation in the depth of the vitreous chamber, thickness of the lens, radius of the anterior surface of the cornea, radius of the anterior surface of the lens, as well as refractive indices for the lens and vitreous, appears to have the largest impact on the refractive error and thus are categorized as critical ocular parameters. The radii of the posterior surfaces of the cornea and lens have much smaller contributions to the refractive state, while the radii of the anterior and posterior surfaces of the retina have no effect on the refractive error. These data provide the framework for further refinement of the optical models of the rat and mouse eye and suggest that extra efforts should be directed towards increasing the linear resolution of the rodent eye biometry and obtaining more accurate data for the refractive indices of the lens and vitreous.

Ocular surface immunity: homeostatic mechanisms and their disruption in dry eye disease.

PubMed

Barabino, Stefano; Chen, Yihe; Chauhan, Sunil; Dana, Reza

2012-05-01

The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others' studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation. Copyright © 2012 Elsevier Ltd. All rights reserved.

Scleral Lenses in the Management of Corneal Irregularity and Ocular Surface Disease.

PubMed

Shorter, Ellen; Harthan, Jennifer; Nau, Cherie B; Nau, Amy; Barr, Joseph T; Hodge, David O; Schornack, Muriel M

2017-09-29

To describe current practice patterns regarding the use of scleral lens therapy in the management of corneal irregularity and ocular surface disease among eye care providers who fit scleral lenses. The Scleral Lenses in Current Ophthalmic Practice: an Evaluation (SCOPE) study group conducted an electronic survey of eye care providers from January 15 to March 31, 2015. Respondents ranked management options for corneal irregularity in the order in which they would generally consider their use. Respondents also ranked options for the management of ocular surface disease in the order in which they would use each of the treatments. Results for each option were analyzed as percentage first-place ranking; percentage first-, second-, or third-place ranking; and mean rank score. Survey responses were obtained from 723 providers who had fit 5 or more scleral lenses. Of these respondents, 629 ranked options for management of corneal irregularity and 612 ranked options for management of ocular surface disease. Corneal rigid gas-permeable lenses were the first option for management of corneal irregularity for 44% of respondents, and scleral lenses were the first option for 34% of respondents. Lubricant drops were the first therapeutic recommendation for ocular surface disease for 84% of respondents, and scleral lenses were ranked first by 6% of respondents. Scleral lenses rank second only to corneal rigid gas-permeable lenses for management of corneal irregularity. Scleral lenses are generally considered after other medical intervention and before surgery for the management of ocular surface disease.

Ocular Surface Immunity: Homeostatic Mechanisms and Their Disruption in Dry Eye Disease

PubMed Central

Barabino, Stefano; Chen, Yihe; Chauhan, Sunil; Dana, Reza

2012-01-01

The tear film, lacrimal glands, corneal and conjunctival epithelia and Meibomian glands work together as a lacrimal functional unit (LFU) to preserve the integrity and function of the ocular surface. The integrity of this unit is necessary for the health and normal function of the eye and visual system. Nervous connections and systemic hormones are well known factors that maintain the homeostasis of the ocular surface. They control the response to internal and external stimuli. Our and others’ studies show that immunological mechanisms also play a pivotal role in regulating the ocular surface environment. Our studies demonstrate how anti-inflammatory factors such as the expression of vascular endothelial growth factor receptor-3 (VEGFR-3) in corneal cells, immature corneal resident antigen-presenting cells, and regulatory T cells play an active role in protecting the ocular surface. Dry eye disease (DED) affects millions of people worldwide and negatively influences the quality of life for patients. In its most severe forms, DED may lead to blindness. The etiology and pathogenesis of DED remain largely unclear. Nonetheless, in this review we summarize the role of the disruption of afferent and efferent immunoregulatory mechanisms that are responsible for the chronicity of the disease, its symptoms, and its clinical signs. We illustrate current anti-inflammatory treatments for DED and propose that prevention of the disruption of immunoregulatory mechanisms may represent a promising therapeutic strategy towards controlling ocular surface inflammation. PMID:22426080

Functional anatomy and immunological interactions of ocular surface and adnexa.

PubMed

Paulsen, Friedrich

2008-01-01

This chapter gives an overview about the structures and physiology of the ocular surface and its adnexa and focuses in a second part on the possible meaning of eye-associated lymphoid tissue (EALT) in a context with the development of dry eye. Sections deal with (1) anatomy of the ocular surface, lacrimal gland, eyelid and nasolacrimal ducts. (2) The meaning and importance of the lacrimal functional unit and the function of the mucosal innate immune system are briefly summarized. (3) Finally, the occurrence and the possible function of EALT is discussed with regard to tolerance induction and dry eye. The epithelial surface of the eye and its specialized glandular infoldings produce the components of the tear film, which include water, protective antimicrobials, cytokines, lipids as well as mucins and trefoil factor family (TFF) peptides. Antimicrobials, mucins and TFF peptides perform a number of essential functions which, collectively, provide protection of the ocular surface. Their production changes in cases of dry eye. The development of EALT is a common feature frequently occurring in symptomatically normal conjunctiva and nasolacrimal ducts. The production of antimicrobials, mucins and TFF peptides can be linked with cell signaling, tear film rheology, and antimicrobial defense at the ocular surface. Changes in the production of such peptides and proteins in cases of dry eye support the assumption that these peptides and proteins are involved in the pathophysiological events that occur at the ocular surface and lacrimal apparatus. Whether special types of bacteria, viruses, or other factors, e.g., immune deviation, are responsible for the development of EALT in humans requires further investigation in prospective and experimental studies.

[Ocular Surface Evaluation in Patients Treated with Prostaglandin Analogues Considering Preservative Agent].

PubMed

Mlčáková, E; Mlčák, P; Karhanová, M; Langová, K; Marešová, K

The aim of this study was to evaluate the ocular surface in patients treated with prostaglandin analogues considering contained preservative agent. 60 patients with glaucoma or ocular hypertension treated with prostaglandin analogue monotherapy were enrolled in this observational study. 20 patients with glaucoma suspect or ocular hypertension without local or systemic glaucoma medication formed the control group. Demographic data and medical history were recorded for each participant. Patients filled in the Ocular surface disease index© (OSDI) questionnaire and underwent an ophthalmological examination including assessment of conjunctival hyperaemia according to Efron, tear film break up time (BUT) and fluorescein staining according to the Oxford grading scheme. Treated participants were divided into 3 groups according to the preservative contained in the currently used prostaglandin analogue: the preservative-free group (18 patients), the polyquaternium group (17 patients) and the benzalkonium chloride (BAK) group (25 patients). The control group had significantly lower fluorescein staining than the preservative-free group (p=0.001), the polyquaternium group (p=0.007) and the BAK group (p=0.002). The conjunctival hyperaemia was significantly lower in the preservative-free group compared to the polyquaternium group (p=0.011). There was no significant difference among the other groups. The difference neither in the OSDI score nor in the BUT was statistically important. This study confirmed that the ocular surface is worse in patients treated with prostaglandin analogue monotherapy than in people without glaucoma medication. A significant difference among treated patients depending on a preservative agent was not proved.Key words: benzalkonium chloride, glaucoma, ocular surface disease, preservatives, prostaglandin analogues.

Dry eye syndrome: developments and lifitegrast in perspective

PubMed Central

Lollett, Ivonne V; Galor, Anat

2018-01-01

Dry eye (DE) is a chronic ocular condition with high prevalence and morbidity. It has a complex pathophysiology and is multifactorial in nature. Chronic ocular surface inflammation has emerged as a key component of DE that is capable of perpetuating ocular surface damage and leading to symptoms of ocular pain, discomfort, and visual phenomena. It begins with stress to the ocular surface leading to the production of proinflammatory mediators that induce maturation of resident antigen-presenting cells which then migrate to the lymph nodes to activate CD4 T cells. The specific antigen(s) targeted by these pathogenic CD4+ T cells remains unknown. Two emerging theories include self-antigens by autoreactive CD4 T cells or harmless exogenous antigens in the setting of mucosal immunotolerance loss. These CD4 T cells migrate to the ocular surface causing additional inflammation and damage. Lifitegrast is the second topical anti-inflammatory agent to be approved by the US Food and Drug Administration for the treatment of DE and the first to show improvement in DE symptoms. Lifitegrast works by blocking the interaction between intercellular adhesion molecule-1 and lymphocyte functional associated antigen-1, which has been shown to be critical for the migration of antigen-presenting cells to the lymph nodes as well as CD4+ T cell activation and migration to the ocular surface. In four large multicenter, randomized controlled trials, lifitegrast has proven to be effective in controlling both the signs and symptoms of DE with minimal side effects. Further research should include comparative and combination studies with other anti-inflammatory therapies used for DE. PMID:29391773

Defensins and Other Antimicrobial Peptides at the Ocular Surface

PubMed Central

McDermott, Alison M.

2006-01-01

Although constantly exposed to the environment and “foreign bodies” such as contact lenses and unwashed fingertips, the ocular surface succumbs to infection relatively infrequently. This is, in large part, due to a very active and robust innate immune response mounted at the ocular surface. Studies over the past 20 years have revealed that small peptides with antimicrobial activity are a major component of the human innate immune response system. The ocular surface is no exception, with peptides of the defensin and cathelicidin families being detected in the tear film and secreted by corneal and conjunctival epithelial cells. There is also much evidence to suggest that the role of some antimicrobial peptides is not restricted to direct killing of pathogens, but, rather, that they function in various aspects of the immune response, including recruitment of immune cells, and through actions on dendritic cells provide a link to adaptive immunity. A role in wound healing is also supported. In this article, the properties, mechanisms of actions and functional roles of antimicrobial peptides are reviewed, with particular emphasis on the potential multifunctional roles of defensins and LL-37 (the only known human cathelicidin) at the ocular surface. PMID:17216098

Polyclonality of Staphylococcus epidermidis residing on the healthy ocular surface.

PubMed

Ueta, Mayumi; Iida, Tetsuya; Sakamoto, Masako; Sotozono, Chie; Takahashi, Junko; Kojima, Kentaro; Okada, Kazuhisa; Chen, Xiuhao; Kinoshita, Shigeru; Honda, Takeshi

2007-01-01

Staphylococcus epidermidis is part of the normal bacterial flora on the ocular surface. The chromosomal DNA of bacterial isolates obtained from the conjunctival sac, upper and lower lid margins, and upper and lower Meibomian glands of healthy volunteers was subjected to SmaI digestion and PFGE to study the genetic diversity of the organisms. Multiple colonies were also examined of S. epidermidis derived from the conjunctival sac of the same subjects. Lastly, commensal bacteria were harvested from the ocular surfaces of four healthy subjects once a month for 6 months, and the genetic background of the S. epidermidis isolates was analysed. It was found that bacterial strains not only from different subjects but also from multiple ocular surface sites of the same subject exhibited different PFGE patterns. In five of 42 subjects multiple colonies of S. epidermidis were isolated from the conjunctival sac; three harboured multiple colonies with different PFGE patterns, and two manifested multiple colonies with identical PFGE patterns. S. epidermidis isolated from the conjunctival sac of the same subjects over a 6-month period exhibited varying PFGE patterns. The data demonstrate the polyclonality of S. epidermidis on the healthy ocular surface.

Contact lens-related dry eye and ocular surface changes with mapping technique in long-term soft silicone hydrogel contact lens wearers.

PubMed

Sengor, Tomris; Aydin Kurna, Sevda; Ozbay, Nurver; Ertek, Semahat; Aki, Suat; Altun, Ahmet

2012-01-01

To evaluate ocular surface changes in long-term silicone hydrogel contact lens wearers. Thirty patients were included in this study. Twenty patients (40 eyes) using contact lenses constituted group 1 and 10 (20 eyes) volunteers constituted group 2. The duration of average contact lens usage was 7.74 ± 3.3 years. Ocular surface was evaluated by surface staining, tear film break-up time (TBUT), Schirmer I test, and conjunctival impression cytology with color-coded mapping technique and by the Ocular Surface Disease Index (OSDI). The mean break-up time was lower and staining scores were higher in group 1 (p<0.001) but Schirmer values were not significantly different from group 2 (p>0.05). The mean OSDI score was 34.59 ± 11.93 to 19.28 ± 6.7 in group 1 and 2. Increased metaplastic predominant changes of grade II and III were observed in the interpalpebral and perilimbal areas in group 1. Significant correlations were observed in TBUT, cornea staining, and grade II to grade III metaplasia ratios between duration of the lens usage and contact lens wear time in a day. Silicone hydrogel lenses produce significant changes on tear film and impression cytology of the ocular surface in long-term use.

The contribution of accommodation and the ocular surface to the microfluctuations of wavefront aberrations of the eye.

PubMed

Zhu, Mingxia; Collins, Michael J; Iskander, D Robert

2006-09-01

We have used videokeratoscopy and wavefront sensing to investigate the contribution of the ocular surface and the effect of stimulus vergence on the microfluctuations of the wavefront aberrations of the eye. The fluctuations of the wavefront aberrations were quantified by their variations around the mean and by using power spectrum analysis. Integrated power was determined in two regions: 0.1-0.7 Hz (low frequencies) and 0.8-1.8 Hz (high frequencies). Changes in the ocular surface topography were measured using high-speed videokeratoscopy and variations in the ocular wavefront aberrations were measured with a wavefront sensor. The microfluctuations of wavefront aberrations of the ocular surface were found to be considerably smaller than the microfluctuations of the wavefront aberrations of the total eye. The fluctuations in defocus while viewing a closer target at 2 or 4 D were found to be significantly greater than fluctuations in defocus when viewing a far target. This increase in defocus fluctuations (p < or = 0.001) occurred in both the low- and high-frequency regions of the power spectra.

Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: A retrospective study

PubMed Central

Sharma, Anjana; Panda, Anita

2007-01-01

Background: The extent of association of human papilloma virus (HPV) in human conjunctival neoplasias has been debated in studies originating from different parts of the world, but no substantial evidence has been generated on Indian subjects. This prompted us to carry out a retrospective study on conjunctival neoplasias diagnosed over the past 12 years. Materials and Methods: Histopathological and immunohistochemical analysis of 65 specimens of ocular neoplasias and 30 normal controls diagnosed between 1991 and 2002 at a tertiary eye care hospital, was undertaken. Formalin-fixed, paraffin-embedded tissues were reviewed for confirming histopathological diagnosis, presence of koilocytosis and changes related to actinic keratosis. Immunohistochemical analysis was done using HPV-specific monoclonal antibodies. Clinicopathological correlation and the association of HPV antigen with the histopathological features were performed. Results: Out of the 65 cases analyzed, 35 were papillomas and 30 were ocular surface squamous neoplasias (OSSN). The mean age was 48 years with a male preponderance. Histologically, koilocytosis was observed in 17.1% of papillomas and 36.6% of OSSN. Actinic keratosis was present in 33% of OSSN. Immunohistochemically 17.1% conjunctival papillomas stained positive for HPV antigen, all cases of OSSN were negative for HPV. There was no correlation between koilocytosis or actinic keratosis and the detection of HPV antigen. Conclusions: The association between HPV and conjunctival neoplasias is variable in different geographical areas and also depends on the methods of detection used. This study warrants the need for applying more advanced techniques at a molecular level to determine the possible etiology of HPV in conjunctival neoplasias among Asian-Indians. PMID:17699945

Penetration of mucoadhesive chitosan-dextran sulfate nanoparticles into the porcine cornea.

PubMed

Chaiyasan, Wanachat; Praputbut, Sakonwun; Kompella, Uday B; Srinivas, Sangly P; Tiyaboonchai, Waree

2017-01-01

Topical application of drugs to the eyes suffers from poor bioavailability at the ocular surface and in the anterior chamber. This is due to rapid clearance of the drug because of tear secretion and outflow. This study has investigated mucoadhesive and penetration characteristics of chitosan-dextran sulfate nanoparticles (CDNs), prepared by polyelectrolyte complexation technique, following topical administration to the ocular surface. Topical FITC-labeled CDNs (FCDNs; mean size of 400nm and a surface charge of +48mV) were retained on the porcine ocular surface for more than 4h. Topical FCDNs were partially endocytosed into porcine corneal epithelial cells via a clathrin-dependent pathway. After 6h of topical FCDNs, particles accumulated in the corneal epithelium but not found in the corneal stroma. When epithelium was removed, FCDNs penetrated the stroma. Thus, CDNs are potentially useful for drug/gene delivery to the ocular surface and to stroma when epithelium is damaged. Copyright © 2016 Elsevier B.V. All rights reserved.

The Effects of Increasing Ocular Surface Stimulation on Blinking and Tear Secretion

PubMed Central

Wu, Ziwei; Begley, Carolyn G.; Port, Nicholas; Bradley, Arthur; Braun, Richard; King-Smith, Ewen

2015-01-01

Purpose. To investigate the effect of varying levels of ocular surface stimulation on the timing and amplitude of the blink and tear secretion. Methods. Following instillation of fluorescein dye, increasing levels of air flow were directed toward the central corneas of 10 healthy subjects. Interblink interval (IBI), tear meniscus height (TMH), and fluorescence intensity were measured simultaneously. Because blinking can obscure changes in TMH, we developed novel measures of tear secretion by calculating tear meniscus fluorescein concentration (TMFC) from intensity using a mathematical model. The change of TMH and TMFC over trials and the slope of the TMFC within each IBI (IBI-TTR) were further calculated. Results. The mean IBI was decreased by 8.08 ± 8.54 seconds from baseline to maximum air stimulation. The TMH increase was highly variable (0.41 ± 0.39 mm) among subjects, compared to the fluorescence tear turnover metrics: decrease in TMFC of 2.84 ± 0.98 natural logarithm or ln(%) and IBI-TTR of 0.065 ± 0.032 ln(%)/sec. Ocular surface stimulation was highly correlated with the TMFC and IBI-TTR, but less so with TMH (Pearson's r = 0.71, 0.69, and 0.40, P < 0.01, respectively). Blinking and tearing were significantly correlated with each other (Pearson's r = 0.56, P < 0.01), but tearing lagged behind by an average of 6.54 ± 4.07 seconds. Conclusions. Blinking and tearing share a common origin with sensory stimulation at the ocular surface. Both showed a dose–response increase with surface stimulation and were correlated with each other. These methods can potentially be used to understand alterations in ocular surface sensory function and associated protective responses in dry eye and other disorders of the ocular surface. PMID:26132780

The Effects of Increasing Ocular Surface Stimulation on Blinking and Tear Secretion.

PubMed

Wu, Ziwei; Begley, Carolyn G; Port, Nicholas; Bradley, Arthur; Braun, Richard; King-Smith, Ewen

2015-07-01

To investigate the effect of varying levels of ocular surface stimulation on the timing and amplitude of the blink and tear secretion. Following instillation of fluorescein dye, increasing levels of air flow were directed toward the central corneas of 10 healthy subjects. Interblink interval (IBI), tear meniscus height (TMH), and fluorescence intensity were measured simultaneously. Because blinking can obscure changes in TMH, we developed novel measures of tear secretion by calculating tear meniscus fluorescein concentration (TMFC) from intensity using a mathematical model. The change of TMH and TMFC over trials and the slope of the TMFC within each IBI (IBI-TTR) were further calculated. The mean IBI was decreased by 8.08 ± 8.54 seconds from baseline to maximum air stimulation. The TMH increase was highly variable (0.41 ± 0.39 mm) among subjects, compared to the fluorescence tear turnover metrics: decrease in TMFC of 2.84 ± 0.98 natural logarithm or ln(%) and IBI-TTR of 0.065 ± 0.032 ln(%)/sec. Ocular surface stimulation was highly correlated with the TMFC and IBI-TTR, but less so with TMH (Pearson's r = 0.71, 0.69, and 0.40, P < 0.01, respectively). Blinking and tearing were significantly correlated with each other (Pearson's r = 0.56, P < 0.01), but tearing lagged behind by an average of 6.54 ± 4.07 seconds. Blinking and tearing share a common origin with sensory stimulation at the ocular surface. Both showed a dose-response increase with surface stimulation and were correlated with each other. These methods can potentially be used to understand alterations in ocular surface sensory function and associated protective responses in dry eye and other disorders of the ocular surface.

A nanomedicine to treat ocular surface inflammation: performance on an experimental dry eye murine model.

PubMed

Contreras-Ruiz, L; Zorzi, G K; Hileeto, D; López-García, A; Calonge, M; Seijo, B; Sánchez, A; Diebold, Y

2013-05-01

MUC5AC is a glycoprotein with gel-forming properties, whose altered expression has been implicated in the pathogenesis of dry eye disease. The aim of our study was to achieve an efficient in vivo transfection of MUC5AC, restore its normal levels in an inflamed ocular surface and determine whether restored MUC5AC levels improve ocular surface inflammation. Cationized gelatin-based nanoparticles (NPs) loaded with a plasmid coding a modified MUC5AC protein (pMUC5AC) were instilled in healthy and experimental dry eye (EDE) mice. MUC5AC expression, clinical signs, corneal fluorescein staining and tear production were evaluated. Ocular specimens were processed for histopathologic evaluation, including goblet cell count and CD4 immunostaining. Neither ocular discomfort nor irritation was observed in vivo after NP treatment. Expression of modified MUC5AC was significantly higher in ocular surface tissue of pMUC5AC-NP-treated animals than that of controls. In healthy mice, pMUC5AC-NPs had no effect on fluorescein staining or tear production. In EDE mice, both parameters significantly improved after pMUC5AC-NP treatment. Anterior eye segment of treated mice showed normal architecture and morphology with lack of remarkable inflammatory changes, and a decrease in CD4+ T-cell infiltration. Thus, pMUC5AC-NPs were well tolerated and able to induce the expression of modified MUC5A in ocular surface tissue, leading to reduction of the inflammation and, consequently improving the associated clinical parameters, such as tear production and fluorescein staining. These results identify a potential application of pMUC5AC-NPs as a new therapeutic modality for the treatment of dry eye disease.

The TFOS International Workshop on Contact Lens Discomfort: Report of the Subcommittee on Neurobiology

PubMed Central

Stapleton, Fiona; Marfurt, Carl; Golebiowski, Blanka; Rosenblatt, Mark; Bereiter, David; Begley, Carolyn; Dartt, Darlene; Gallar, Juana; Belmonte, Carlos; Hamrah, Pedram; Willcox, Mark

2013-01-01

This report characterizes the neurobiology of the ocular surface and highlights relevant mechanisms that may underpin contact lens–related discomfort. While there is limited evidence for the mechanisms involved in contact lens–related discomfort, neurobiological mechanisms in dry eye disease, the inflammatory pathway, the effect of hyperosmolarity on ocular surface nociceptors, and subsequent sensory processing of ocular pain and discomfort have been at least partly elucidated and are presented herein to provide insight in this new arena. The stimulus to the ocular surface from a contact lens is likely to be complex and multifactorial, including components of osmolarity, solution effects, desiccation, thermal effects, inflammation, friction, and mechanical stimulation. Sensory input will arise from stimulation of the lid margin, palpebral and bulbar conjunctiva, and the cornea. PMID:24058137

Isolation of the ocular surface to treat dysfunctional tear syndrome associated with computer use.

PubMed

Yee, Richard W; Sperling, Harry G; Kattek, Ashballa; Paukert, Martin T; Dawson, Kevin; Garcia, Marcie; Hilsenbeck, Susan

2007-10-01

Dysfunctional tear syndrome (DTS) associated with computer use is characterized by mild irritation, itching, redness, and intermittent tearing after extended staring. It frequently involves foreign body or sandy sensation, blurring of vision, and fatigue, worsening especially at the end of the day. We undertook a study to determine the effectiveness of periocular isolation using microenvironment glasses (MEGS) alone and in combination with artificial tears in alleviating the symptoms and signs of dry eye related to computer use. At the same time, we evaluated the relative ability of a battery of clinical tests for dry eye to distinguish dry eyes from normal eyes in heavy computer users. Forty adult subjects who used computers 3 hours or more per day were divided into dry eye sufferers and controls based on their scores on the Ocular Surface Disease Index (OSDI). Baseline scores were recorded and ocular surface assessments were made. On four subsequent visits, the subjects played a computer game for 30 minutes in a controlled environment, during which one of four treatment conditions were applied, in random order, to each subject: 1) no treatment, 2) artificial tears, 3) MEGS, and 4) artificial tears combined with MEGS. Immediately after each session, subjects were tested on: a subjective comfort questionnaire, tear breakup time (TBUT), fluorescein staining, lissamine green staining, and conjunctival injection. In this study, a significant correlation was found between cumulative lifetime computer use and ocular surface disorder, as measured by the standardized OSDI index. The experimental and control subjects were significantly different (P<0.05) in the meibomian gland assessment and TBUT; they were consistently different in fluorescein and lissamine green staining, but with P>0.05. Isolation of the ocular surface alone produced significant improvements in comfort scores and TBUT and a consistent trend of improvement in fluorescein staining and lissamine green staining. Isolation plus tears produced a significant improvement in lissamine green staining. The subjective comfort inventory and the TBUT test were most effective in distinguishing between the treatments used. Computer users with ocular surface complaints should have a detailed ocular surface examination and, if symptomatic, they can be effectively treated with isolation of the ocular surface, artificial tears therapy, and effective environmental manipulations.

Xeroderma pigmentosum with melanoma of face and its prosthetic management.

PubMed

Sadaf, Ayesha; Yazdanie, Nazia

2013-10-01

Xeroderma pigmentosum is a rare genetic disorder, characterized by cutaneous, ocular and neurological symptoms. Squamous cell carcinoma and melanoma are also its secondary characters. This case report is about maxillofacial prosthetic management of a 10 years old child presented with xeroderma pigmentosum. The nose of the patient was excised surgically due to melanoma. This case report elaborates the role of prosthodontist and the whole procedure of constructing the nasal prosthesis via conventional technique by using the patient's sibling nasal form as template. Regular follow up revealed marked improvement in esthetics, function and ultimately patient's quality of life.

A Review of Ocular Graft-Versus-Host Disease.

PubMed

Munir, Saleha Z; Aylward, James

2017-05-01

: Graft-versus-host disease (GVHD) is a major complication that occurs following allogeneic hematopoietic stem cell transplantation, which is a potential curative therapy used in a variety of malignant or benign hematological diseases. Graft-versus-host disease primarily occurs in many organs, but most notably in the skin, lungs, gastrointestinal tract, liver, eyes, mucosa, and musculoskeletal system. Ocular manifestations of GVHD may precede other systemic GVHD findings, and it may be a poor prognosis for mortality. While all parts of the eye may be affected, ocular GVHD occurs primarily in the ocular surface. Dry eye disease or keratoconjunctivitis sicca is the most common presenting manifestation of chronic ocular GVHD. Dry eye disease in ocular GVHD is a multifactorial process, which involves destruction and fibrosis of lacrimal glands and conjunctiva, leading to tear film deficiency and instability. Depending on the severity of ocular involvement and response to treatment, ocular GVHD may cause decreased quality of life. Management of GVHD begins with prevention by understanding risk factors and by implementing prophylactic treatment after allogeneic hematopoietic stem cell transplantation. A multidisciplinary approach to the prevention and treatment of GVHD is important, and there are currently no preventive therapies available for ocular GVHD. Once diagnosed, ocular GVHD treatment strategies target ocular surface lubrication and support, tear film stabilization, inflammation reduction, and surgical intervention. The goal of this review is to define ocular GVHD and its categorical manifestations, as well as to describe the importance of comprehensive assessment, diagnosis, and ophthalmologic treatment and management of ocular GVHD with a multidisciplinary approach.

Antibacterial activity of dilute povidone-iodine solutions used for ocular surface disinfection in dogs.

PubMed

Roberts, S M; Severin, G A; Lavach, J D

1986-06-01

Bacterial cultures of specimens from healthy canine eyelids and ocular surfaces were found to demonstrate bacterial growth in 69.7% (53/76) of the eyes sampled. Organisms most commonly isolated included: Staphylococcus aureus, alpha-hemolytic Streptococcus sp, S epidermidis, and Escherichia coli. Evaluation of dilute povidone-iodine solutions for effectiveness as ocular surface disinfectants was conducted. Bacterial growth initially detected in 32 of 46 eyes was not detected after disinfection with a 2-minute scrub and 2-minute soaking procedure, using 1:2, 1:10, or 1:50 dilutions of a povidone-iodine solution that contained 1% available iodine. The eyelid and ocular surfaces of 16 eyes were disinfected with 1:100 povidone-iodine solution. Bacterial growth initially present in 10 of 16 eyes was present in 1 eye after disinfection and consisted of a single colony of E coli. After eyes were disinfected with 1:10, 1:50, or 1:100 povidone-iodine solutions, there was no evidence of corneal epithelial edema or sloughing. In 15 eyes subjected to disinfection with the 1:2 dilution, one instance of epithelial corneal edema was noticed. A 1:50 dilution of povidone-iodine is recommended as an ocular surface disinfectant for use in presurgical situations.

Therapeutic inhibitors for the treatment of dry eye syndrome.

PubMed

Rodríguez-Pomar, Candela; Pintor, Jesus; Colligris, Basilio; Carracedo, Gonzalo

2017-12-01

Dry eye disease (DED), defined as a multifactorial disease of tears and ocular surface, results in symptoms of discomfort, ocular irritation, visual disturbance and tear film instability. This syndrome is accompanied of ocular surface inflammation and it is produced by a deficient activity of the lacrimal functional unit. In addition, it is associated with systemic autoimmune diseases such as Sjögren´s Syndrome, rheumatoid arthritis, systemic lupus erythematosus and some drug administration. The treatment of dry eye disease is based on the typical signs and symptoms of dry eye, which are associated with hyperosmolarity, ocular surface inflammation, discomfort, visual disturbance, and tear film instability. Areas covered: This review is focused on synthetic drugs currently used in clinical practice, from phase III development onwards to treat the ocular surface signs and symptoms of dry eye disease. Expert opinion: The multifactorial disease and the lack of correlation between signs and symptoms imply that not all the pharmacological approaches will be successful for dry eye. The correct design of the clinical trials, with appropriate endpoints, and the type of dry eye under study are complicated but mandatory. The anti-inflammatory and secretagogues drugs are both the main compounds to currently treat the dry eye disease.

Adjunctive radiotherapy with strontium-90 in the treatment of conjunctival squamous cell carcinoma.

PubMed

Kearsley, J H; Fitchew, R S; Taylor, R G

1988-03-01

Squamous cell carcinoma of the ocular conjunctiva is a relatively rare malignancy which is attended by a high rate of local recurrence following simple surgical excision. To date, the management of conjunctival squamous cell cancer has been controversial. From 1950 to 1985, 146 consecutive patients with superficial conjunctival squamous cell cancer were treated at the Queensland Radium Institute. All patients were treated by simple surgical excision of the visible conjunctival lesion followed by adjunctive radiotherapy. Of 140 patients with histologically confirmed squamous cell cancer, 123 were treated with a strontium-90 source, 10 with a radon "ring," and 7 with superficial X ray therapy. Standard policy since 1960 has been to deliver an incident dose of 30 Gy in a single fraction within the first 48 post-operative hours to the surgical bed using a strontium-90 source on a stand-off eye applicator. This report will largely focus on the 123 patients who were treated with a strontium-90 source, of whom 107 received 30 Gy, 14 received 40 Gy (pre 1960) and one patient each received 20 and 25 Gy incident dose. Of 131 evaluable patients, there were only 3 who developed local recurrence. All 3 local recurrences developed in elderly men who had presented with extensive superficial primary tumors. Two of the three recurrences occurred in the two patients who were treated with doses less than 30 Gy. Both early and late radiation-induced complications following ablative surgery and treatment with strontium-90 were very uncommon. Three patients developed unsightly conjunctival telangiectasia, 2 patients developed a persistent scleral ulcer and 2 patients developed clinically significant cataracts. This negligible degree of treatment-related side effects contrasts with the experience of 10 patients who had previously been treated with a radon ring, 8 of whom developed serious complications, although none developed local recurrence. On the basis of our excellent local control rates with minimal morbidity we would continue to advocate the use of simple surgical excision followed by 30 Gy beta radiation from a strontium-90 source as the definitive treatment for superficial conjunctival squamous cell cancer.

Ocular Surface Symptoms in Veterans Returning From Operation Iraqi Freedom and Operation Enduring Freedom

PubMed Central

Modi, Yasha S.; Qurban, Qirat; Zlotcavitch, Leonid; Echeverri, Roberto J.; Feuer, William; Florez, Hermes; Galor, Anat

2014-01-01

Purpose. To correlate situational exposures and psychiatric disease with self-reported ocular surface symptoms in a younger veteran population involved in Operation Iraqi Freedom and Operation Enduring Freedom (OIF/OEF). Methods. Cross-sectional study of all veterans evaluated in the OIF/OEF clinic between December 2012 and April 2013 who completed the dry eye questionnaire and screening evaluations for environmental exposures, posttraumatic stress disorder (PTSD), and depression. The main outcome measures were the influence of environmental exposure and psychiatric disease on ocular surface symptoms. Results. Of 115 participants, the average age was 33 years. While overseas, exposure to incinerated waste (odds ratio [OR] 2.67, 95% confidence interval [CI] 1.23–5.81, P = 0.02) and PTSD (OR 2.68, 95% CI 1.23–5.85, P = 0.02) were associated with self-reported ocular surface symptoms. On return to the United States, older age (OR per decade 2.66, 95% CI 1.65–4.31, P = 0.04) was associated with persistent symptoms and incinerated waste was associated with resolution of symptoms (OR 0.25, 95% CI 0.07–0.90, P = 0.04). When evaluating symptom severity, 26% of the responders complained of severe ocular surface symptoms, with PTSD (OR 3.10, 95% CI 1.22–7.88, P = 0.02) and depression (OR 4.28, 95% CI 1.71–10.68, P = 0.002) being significant risk factors for their presence. Conclusions. PTSD was significantly associated with ocular surface symptoms both abroad and on return to the United States, whereas air pollution in the form of incinerated waste, was correlated with reversible symptoms. PMID:24408975

Clinical evaluation of accommodation and ocular surface stability relavant to visual asthenopia with 3D displays

PubMed Central

2014-01-01

Background To validate the association between accommodation and visual asthenopia by measuring objective accommodative amplitude with the Optical Quality Analysis System (OQAS®, Visiometrics, Terrassa, Spain), and to investigate associations among accommodation, ocular surface instability, and visual asthenopia while viewing 3D displays. Methods Fifteen normal adults without any ocular disease or surgical history watched the same 3D and 2D displays for 30 minutes. Accommodative ability, ocular protection index (OPI), and total ocular symptom scores were evaluated before and after viewing the 3D and 2D displays. Accommodative ability was evaluated by the near point of accommodation (NPA) and OQAS to ensure reliability. The OPI was calculated by dividing the tear breakup time (TBUT) by the interblink interval (IBI). The changes in accommodative ability, OPI, and total ocular symptom scores after viewing 3D and 2D displays were evaluated. Results Accommodative ability evaluated by NPA and OQAS, OPI, and total ocular symptom scores changed significantly after 3D viewing (p = 0.005, 0.003, 0.006, and 0.003, respectively), but yielded no difference after 2D viewing. The objective measurement by OQAS verified the decrease of accommodative ability while viewing 3D displays. The change of NPA, OPI, and total ocular symptom scores after 3D viewing had a significant correlation (p < 0.05), implying direct associations among these factors. Conclusions The decrease of accommodative ability after 3D viewing was validated by both subjective and objective methods in our study. Further, the deterioration of accommodative ability and ocular surface stability may be causative factors of visual asthenopia in individuals viewing 3D displays. PMID:24612686

PRESERVATIVES FROM THE EYE DROPS AND THE OCULAR SURFACE

PubMed Central

Coroi, Mihaela Cristina; Bungau, Simona; Tit, Mirela

2015-01-01

The use of preservatives in eye drops (eyewashes) has known glory at the beginning, but the side effects that they have on the ocular surface have led to a decrease of their popularity. Lachrymal film dysfunction, ocular hyperemia, dotted keratitis or toxic keratopathy were reported and analyzed in terms of pathophysiological mechanism of the role played by preservatives in ophthalmic drops (eyewashes). This article reviews the most common preservatives and the existing alternatives for the maintenance of the eye sterile drops. PMID:27373107

Requirement of Smad4 from Ocular Surface Ectoderm for Retinal Development.

PubMed

Li, Jing; Wang, Shusheng; Anderson, Chastain; Zhao, Fangkun; Qin, Yu; Wu, Di; Wu, Xinwei; Liu, Jia; He, Xuefei; Zhao, Jiangyue; Zhang, Jinsong

2016-01-01

Microphthalmia is characterized by abnormally small eyes and usually retinal dysplasia, accounting for up to 11% of the blindness in children. Right now there is no effective treatment for the disease, and the underlying mechanisms, especially how retinal dysplasia develops from microphthalmia and whether it depends on the signals from lens ectoderm are still unclear. Mutations in genes of the TGF-β superfamily have been noted in patients with microphthalmia. Using conditional knockout mice, here we address the question that whether ocular surface ectoderm-derived Smad4 modulates retinal development. We found that loss of Smad4 specifically on surface lens ectoderm leads to microphthalmia and dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the delayed or failed differentiation and apoptosis of retinal cells. Microarray analyses revealed that members of Hedgehog and Wnt signaling pathways are affected in the knockout retinas, suggesting that ocular surface ectoderm-derived Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest that defective of ocular surface ectoderm may affect retinal development.

Requirement of Smad4 from Ocular Surface Ectoderm for Retinal Development

PubMed Central

Li, Jing; Wang, Shusheng; Anderson, Chastain; Zhao, Fangkun; Qin, Yu; Wu, Di; Wu, Xinwei; Liu, Jia; He, Xuefei; Zhao, Jiangyue; Zhang, Jinsong

2016-01-01

Microphthalmia is characterized by abnormally small eyes and usually retinal dysplasia, accounting for up to 11% of the blindness in children. Right now there is no effective treatment for the disease, and the underlying mechanisms, especially how retinal dysplasia develops from microphthalmia and whether it depends on the signals from lens ectoderm are still unclear. Mutations in genes of the TGF-β superfamily have been noted in patients with microphthalmia. Using conditional knockout mice, here we address the question that whether ocular surface ectoderm-derived Smad4 modulates retinal development. We found that loss of Smad4 specifically on surface lens ectoderm leads to microphthalmia and dysplasia of retina. Retinal dysplasia in the knockout mice is caused by the delayed or failed differentiation and apoptosis of retinal cells. Microarray analyses revealed that members of Hedgehog and Wnt signaling pathways are affected in the knockout retinas, suggesting that ocular surface ectoderm-derived Smad4 can regulate Hedgehog and Wnt signaling in the retina. Our studies suggest that defective of ocular surface ectoderm may affect retinal development. PMID:27494603

The Relationship Between High-Order Aberration and Anterior Ocular Biometry During Accommodation in Young Healthy Adults

PubMed Central

Ke, Bilian; Mao, Xinjie; Jiang, Hong; He, Jichang; Liu, Che; Li, Min; Yuan, Ying

2017-01-01

Purpose This study investigated the anterior ocular anatomic origin of high-order aberration (HOA) components using optical coherence tomography and a Shack-Hartmann wavefront sensor. Methods A customized system was built to simultaneously capture images of ocular wavefront aberrations and anterior ocular biometry. Relaxed, 2-diopter (D) and 4-D accommodative states were repeatedly measured in 30 young subjects. Custom software was used to correct optical distortions and measure biometric parameters from the images. Results The anterior ocular biometry changed during 2-D accommodation, in which central lens thickness, ciliary muscle thicknesses at 1 mm posterior to the scleral spur (CMT1), and the maximum value of ciliary muscle thickness increased significantly, whereas anterior chamber depth, CMT3, radius of anterior lens surface curvature (RAL), and radius of posterior lens surface curvature (RPL) decreased significantly. The changes in the anterior ocular parameters during 4-D accommodation were similar to those for the 2-D accommodation. \\begin{document}\

The leaves of Diospyros kaki exert beneficial effects on a benzalkonium chloride-induced murine dry eye model.

PubMed

Kim, Kyung-A; Hyun, Lee Chung; Jung, Sang Hoon; Yang, Sung Jae

2016-01-01

In this study, the beneficial effects of the oral administration of ethanol extract of Diospyros kaki (EEDK) were tested on a mouse dry eye model induced by benzalkonium chloride (BAC). A solution of 0.2% BAC was administered topically to mouse eyes for 14 days, twice daily, to induce dry eye. Various concentrations of EEDK were administrated daily by oral gavage for 14 days after BAC treatment. Preservative-free eye drops were instilled in the positive-control group. The tear secretion volume (Schirmer's test), tear break-up time (BUT), and fluorescein score were measured on the ocular surface. BAC-induced corneal damage was tested with hematoxylin-eosin staining. Moreover, apoptotic cell death in the corneal epithelial layer was investigated with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. The protein expression level of interleukin-1alpha (IL-1α), IL-1β, IL-6, tumor necrosis factor- alpha (TNF-α), and monocyte chemotactic protein-1 (MCP-1) was determined with western blot analysis. Furthermore, squamous metaplasia in the corneal epithelial layer was detected with immunofluorescent staining for cytokeratine-10. The cellular proliferation in the cornea was examined with immunohistochemical staining for Ki-67. EEDK treatment resulted in prolonged BUT, decreased fluorescein score, increased tear volume, and smoother epithelial cells compared with BAC treatment alone in the cornea. Moreover, EEDK treatment inhibited the inflammatory response and corneal epithelial cell death in a BAC-induced murine dry eye model, and changes in squamous cells were inhibited. Proliferative activity in the corneal epithelium cells was improved with EEDK. EEDK could be a potential therapeutic agent in the clinical treatment of dry eye.

Glycobiology of the ocular surface: Mucins and lectins

PubMed Central

Argüeso, Pablo

2013-01-01

Glycosylation is an important and common form of posttranscriptional modification of proteins in cells. A vast array of biological functions has been ascribed to glycans during the last decade thanks to a rapid evolution in glycomic technologies. Glycogenes highly expressed at the human ocular surface include families of glycosyltransferases, proteoglycans, glycan degradation proteins, as well as mucins and carbohydrate-binding proteins such as the galectins. On the apical glycocalyx, mucin O-glycans promote boundary lubrication, prevent bacterial adhesion and endocytic activity, and maintain epithelial barrier function through interactions with galectins. The emerging roles attributed to glycans are contributing to the appreciation of their biological capabilities at the ocular surface. PMID:23325272

Improvements in Signs and Symptoms of Dry Eye after Instillation of 2% Rebamipide.

PubMed

Igarashi, Tsutomu; Fujita, Miho; Yamada, Yumi; Kobayashi, Maika; Fujimoto, Chiaki; Takahashi, Hisatomo; Igarashi, Toru; Nakano, Yuichiro; Suzuki, Hisaharu; Takahashi, Hiroshi

2015-01-01

Because dry eye greatly reduces quality of life, this study aimed to examine rebamipide instillation in patients with dry eye and assess the improvement of signs and symptoms as evaluated with the Ocular Surface Disease Index, which is the most popular index and is highly reliable. From June 2013 through January 2014, we examined 50 eyes of 25 patients with dry eye (6 men and 19 woman) at our institution. Dry eye was diagnosed on the basis of the presence of symptoms, tear dynamics, and ocular surface abnormalities according to the Japanese criteria for dry eye. Before being enrolled, all patients underwent ocular surface health assessment, including history interviews, and completed the Ocular Surface Disease Index questionnaire. Patients received 2% rebamipide ophthalmic solution 4 times daily for 4 weeks. Signs and symptoms were analyzed before and 4 weeks after rebamipide administration. Tear dynamics, tear break-up time, and ocular surface abnormalities were measured and compared between before and 4 weeks after rebamipide administration. Of the 25 patients, 9 had definite dry eye and 16 had probable dry eye. Tear break-up time and the fluorescein staining score significantly improved after 4 weeks. However, no significant change was observed for the Schirmer test I and the lissamine green staining score. The administration of 2% rebamipide 4 times daily for 4 weeks improves the signs and symptoms of dry eye and improves patients' quality of life.

Plasma Rich in Growth Factors for the Treatment of Ocular Surface Diseases.

PubMed

Anitua, Eduardo; Muruzabal, Francisco; de la Fuente, María; Merayo, Jesús; Durán, Juan; Orive, Gorka

2016-07-01

The purpose of this work is to describe and review the technology of plasma rich in growth factors (PRGF), a novel blood derivative product, in the treatment of ocular surface disorders. To demonstrate the importance of this technology in the treatment of ocular pathologies, a thorough review of the preclinical and clinical literature results obtained following use of the different therapeutic formulations of PRGF was carried out. A literature search for applications of PGRF plasma in the ophthalmology field was carried out using the PubMed database. PRGF involves the use of patient's own biologically active proteins, growth factors, and biomaterial scaffolds for therapeutic purposes. This procedural technology is gaining interest in regenerative medicine due to its potential to stimulate and accelerate the tissue healing processes. The versatility and biocompatibility of this technology opens the door to a personalized medicine on ocular tissue regeneration. This review discusses the state of the art of the new treatments and technologies developed to promote ocular surface tissue regeneration. The standardized protocol that has been developed to source eye drops from PRGF technology is also described. The preclinical research, together with the most relevant clinical applications are summarized and discussed. The preliminary results suggest that the use of PRGF to enhance ocular tissue regeneration is safe and efficient.

Impact of wildfire smoke in Buenos Aires, Argentina, on ocular surface.

PubMed

Berra, Martin; Galperín, Gustavo; Dawidowski, Laura; Tau, Julia; Márquez, Isabel; Berra, Alejandro

2015-01-01

To evaluate the acute impact of the wildfire smoke episode in 2008 on the ocular surface of subjects living in the Metropolitan Area of Buenos Aires (MABA). A total of 86 subjects were evaluated: Group 1 comprised patients from a public ophthalmology hospital (N=35) and Group 2 comprised healthy volunteers (N=51). All subjects answered a questionnaire on ocular symptoms and underwent ophthalmologic examination [bulbar conjunctival hyperemia, corneal fluorescein staining, rose bengal vital staining, tear break-up time (TBUT), Schirmer I test, tear lysozyme, and impression cytology] during and after the acute episode. Concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), and particulate matter (PM) were measured before, during, and after the acute episode. Both groups showed a statically significant increase in ocular symptoms and bulbar conjunctival hyperemia and a statically significant decrease in tear break-up time during the acute episode. Group 1 showed more severe symptoms and a statistically significant increase in fluorescein and rose bengal staining intensities during the acute episode. We found a significant negative correlation between ocular symptoms and tear break-up time. During the episode, the levels of CO, NO2, and particulate matter in MABA were four times higher than the usual average levels for the same period in 2007 and 2009. Increased air pollution from the burning of biomass is associated with a decrease in the stability of the tear film (TBUT), generating areas of ocular surface exposure that may be the cause of the increased feeling of irritation. Group 1 was more affected by not having a healthy ocular surface, and thus consulted an ophthalmologist. Cytological changes in the conjunctiva were not observed, which could be due to the short duration of the episode.

Association between clinical diagnostic tests and health-related quality of life surveys in patients with dry eye syndrome.

PubMed

Mizuno, Yoshinobu; Yamada, Masakazu; Miyake, Yozo

2010-07-01

This study was performed to assess the impact of dry eye on patients' quality of life (QOL) and to analyze the association between subjective symptoms and ocular surface findings of dry eye. The study population consisted of 158 patients with dry eye aged 20 years or older who visited any of the 15 medical care facilities enrolled in the study. The backgrounds and ocular findings of the patients were investigated, and their QOL was evaluated with the Japanese version of the 25-item National Eye Institute Visual Functioning Questionnaire (VFQ-25) and of the Medical Outcomes Study (MOS) 8-item Short-Form Health Survey (SF-8) to examine the association between subjective symptoms and ocular surface findings. Of the patients enrolled, 15 were men and 143 were women, and their average age was 62.5 +/- 12.6 years. Sixty patients (38.0%) had comorbid Sjögren syndrome (SS). The results of Schirmer testing, fluorescein staining, and rose bengal staining for SS patients were significantly worse than those for the non-SS patients, but the VFQ-25 and SF-8 scores were not significantly different between the SS and non-SS patients. In the ocular surface findings, a weak association between the fluorescein staining scores and general vision scores, a subscale of the VFQ-25, was found. However, the ocular surface findings and VFQ-25/SF-8 results in the simple correlation analysis as well as in the multiple linear regression analysis showed no significant associations. Ocular surface findings and QOL scores of patients with dry eye appear to disagree. Therefore, it is necessary to address subjective symptoms and QOL scores in addition to examination findings when evaluating dry eye.

Expression of prostaglandin E receptor subtype EP4 in conjunctival epithelium of patients with ocular surface disorders: case-control study.

PubMed

Ueta, Mayumi; Sotozono, Chie; Yamada, Keiko; Yokoi, Norihiko; Inatomi, Tsutomu; Kinoshita, Shigeru

2012-01-01

To confirm the downregulation of PTGER4 mRNA in the conjunctiva of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and ocular cicatricial pemphigoid (OCP) patients and to examine the expression of its EP4 protein in the conjunctival epithelium of patients with various ocular surface disorders. Case-control study. We performed quantitative reverse transcription-PCR (RT-PCR) analysis of PTGER4 mRNA in conjunctival tissue sections from patients with SJS/TEN and OCP to confirm the downregulation of PTGER4 mRNA expression. We also analysed EP4 immunohistologically in other ocular surface disorders. Conjunctival tissues were obtained from patients undergoing surgical reconstruction of the ocular surface due to chemical eye burns, subacute SJS/TEN or chronic SJS/TEN, chronic OCP, severe graft versus host disease (GVHD) and from patients with Mooren's ulcers treated by resection of the inflammatory conjunctiva. The expression of PTGER4 mRNA and EP4 protein assessed by quantitative RT-PCR assay and immunohistological methods. PTGER4 mRNA was significantly lower in conjunctival tissues from SJS and OCP patients than in the control conjunctivochalasis samples. EP4 protein was detected in conjunctival epithelium from patients with chemical eye burn and in control conjunctival epithelium from patients with conjunctivochalasis. Its expression varied in conjunctival epithelium from patients with Mooren's ulcer. We did not detect EP4 immunoreactivity in conjunctival epithelium from patients with subacute SJS/TEN, severe GVHD, chronic SJS/TEN or OCP. The strong downregulation of EP4 expression in conjunctival epithelium from patients with OCP or SJS/TEN may be attributable to ocular surface inflammation.

Expression of prostaglandin E receptor subtype EP4 in conjunctival epithelium of patients with ocular surface disorders: case-control study

PubMed Central

Ueta, Mayumi; Sotozono, Chie; Yamada, Keiko; Yokoi, Norihiko; Inatomi, Tsutomu; Kinoshita, Shigeru

2012-01-01

Objectives To confirm the downregulation of PTGER4 mRNA in the conjunctiva of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) and ocular cicatricial pemphigoid (OCP) patients and to examine the expression of its EP4 protein in the conjunctival epithelium of patients with various ocular surface disorders. Design Case-control study. Setting and participants We performed quantitative reverse transcription-PCR (RT-PCR) analysis of PTGER4 mRNA in conjunctival tissue sections from patients with SJS/TEN and OCP to confirm the downregulation of PTGER4 mRNA expression. We also analysed EP4 immunohistologically in other ocular surface disorders. Conjunctival tissues were obtained from patients undergoing surgical reconstruction of the ocular surface due to chemical eye burns, subacute SJS/TEN or chronic SJS/TEN, chronic OCP, severe graft versus host disease (GVHD) and from patients with Mooren's ulcers treated by resection of the inflammatory conjunctiva. Primary and secondary outcome measures The expression of PTGER4 mRNA and EP4 protein assessed by quantitative RT-PCR assay and immunohistological methods. Results PTGER4 mRNA was significantly lower in conjunctival tissues from SJS and OCP patients than in the control conjunctivochalasis samples. EP4 protein was detected in conjunctival epithelium from patients with chemical eye burn and in control conjunctival epithelium from patients with conjunctivochalasis. Its expression varied in conjunctival epithelium from patients with Mooren's ulcer. We did not detect EP4 immunoreactivity in conjunctival epithelium from patients with subacute SJS/TEN, severe GVHD, chronic SJS/TEN or OCP. Conclusions The strong downregulation of EP4 expression in conjunctival epithelium from patients with OCP or SJS/TEN may be attributable to ocular surface inflammation. PMID:23065448

The Ocular Surface Chemical Burns

PubMed Central

Baradaran-Rafii, Alireza; Djalilian, Ali R.

2014-01-01

Ocular chemical burns are common and serious ocular emergencies that require immediate and intensive evaluation and care. The victims of such incidents are usually young, and therefore loss of vision and disfigurement could dramatically affect their lives. The clinical course can be divided into immediate, acute, early, and late reparative phases. The degree of limbal, corneal, and conjunctival involvement at the time of injury is critically associated with prognosis. The treatment starts with simple but vision saving steps and is continued with complicated surgical procedures later in the course of the disease. The goal of treatment is to restore the normal ocular surface anatomy and function. Limbal stem cell transplantation, amniotic membrane transplantation, and ultimately keratoprosthesis may be indicated depending on the patients' needs. PMID:25105018

[The epithelial junctional zones of the anal canal and cervix uterus: the ultrastructure of tumors of these zones].

PubMed

Chernyĭ, A P; Iakovleva, N I

1990-01-01

Relationships between squamous and columnar epithelia in the anal canal and cervix uteri of postnatal period and fetus were studied. The transitional stratified epithelial lining, which is called junctional epithelium, is interposed between the mentioned epithelia. The junctional epithelium has variable numbers of layers of epidermoid cells, which differ from cells of atypical squamous epithelium by some ultrastructural features of the cytoskeleton and cell surface and by a low content of glycogen. The hypothesis on the physiological significance of this epithelium is proposed. Ultrastructural features of the cytoskeleton and cell surface suggest that anal basaloid carcinomas and some cervical squamous carcinomas may develop from so-called junctional epithelium.

Efficacy and Safety of Carbomer-Based Lipid-Containing Artificial Tear Formulations in Patients With Dry Eye Syndrome.

PubMed

Chung, So-Hyang; Lim, Sung A; Tchach, Hungwon

2016-02-01

To evaluate the efficacy and safety profile of carbomer-based lipid-containing artificial tear formulations (CBLAT) in patients with dry eye syndrome. A multicenter parallel-group study was conducted in 412 patients with dry eye syndrome. Of these patients, 221 switched from using artificial tears to CBLAT (switching group) and 191 added CBLAT to their current treatment (add-on group). Ocular symptom scores, ocular staining grades, tear film breakup time (tBUT), Schirmer I test value, and Korean dry eye level (as defined by the Korean Corneal Disease Study Group guidelines) were evaluated at baseline and after 4 weeks of treatment. After 4 weeks of treatment, ocular surface staining grade, tBUT, Schirmer I value, ocular irritation symptom scores, and the positive rate of visual symptom improved significantly in both groups. Mean reductions in ocular surface staining grades (-0.8 ± 0.9) and ocular irritation symptom scores (-0.8 ± 0.8) in the add-on group were significantly higher than those (-0.5 ± 0.8 and -0.6 ± 0.8) in the switching group (P < 0.01 and P < 0.05). The positive rate of visual symptoms (44.2%) in the add-on group was significantly higher than that (26.4%) in the switching group (P < 0.01). The decrease of Korean dry eye level was 30.1% in the switching group and 51.6% in the add-on group. More patients in the add-on group had decreased dry eye levels than those in the switching group (P < 0.0001). CBLAT improves ocular surface staining grades, tBUT, Schirmer I values, and ocular symptoms in patients with dry eye syndrome.

Dry Eye as a Mucosal Autoimmune Disease

PubMed Central

Stern, Michael E.; Schaumburg, Chris S.; Pflugfelder, Stephen C.

2013-01-01

Dry eye is a common ocular surface inflammatory disease that significantly affects quality of life. Dysfunction of the lacrimal function unit (LFU) alters tear composition and breaks ocular surface homeostasis, facilitating chronic inflammation and tissue damage. Accordingly, the most effective treatments to date are geared towards reducing inflammation and restoring normal tear film. The pathogenic role of CD4+ T cells is well known, and the field is rapidly realizing the complexity of other innate and adaptive immune factors involved in the development and progression of disease. The data support the hypothesis that dry eye is a localized autoimmune disease originating from an imbalance in the protective immunoregulatory and proinflammatory pathways of the ocular surface. PMID:23360156

Detection of squamous carcinoma cells using gold nanoparticles

NASA Astrophysics Data System (ADS)

Dai, Wei-Yun; Lee, Sze-tsen; Hsu, Yih-Chih

2015-03-01

The goal of this study is to use gold nanoparticle as a diagnostic agent to detect human squamous carcinoma cells. Gold nanoparticles were synthesized and the gold nanoparticle size was 34.3 ± 6.2 nm. Based on the over-expression of epidermal growth factor receptor (EGFR) biomarkers in squamous carcinoma cells, we hypothesized that EGFR could be a feasible biomarker with a target moiety for detection. We further modified polyclonal antibodies of EGFR on the surface of gold nanoparticles. We found selected squamous carcinoma cells can be selectively detected using EGFR antibody-modified gold nanoparticles via receptor-mediated endocytosis. Cell death was also examined to determine the survival status of squamous carcinoma cells with respect to gold nanoparticle treatment and EGFR polyclonal antibody modification.

The role of the lacrimal functional unit in the pathophysiology of dry eye.

PubMed

Stern, Michael E; Gao, Jianping; Siemasko, Karyn F; Beuerman, Roger W; Pflugfelder, Stephen C

2004-03-01

The majority of dry eye symptoms are due to a chronic inflammation of the lacrimal functional unit resulting in a loss of tear film integrity and normal function. This leads to a reduction in the ability of the ocular surface to respond to environmental challenges. The underlying cause of tear film dysfunction is the alteration of tear aqueous, mucin, and lipid components. This may result from a systemic autoimmune disease or a local autoimmune event. A lack of systemic androgen support to the lacrimal gland has been shown to be a facilitative factor in the initiation of this type of pathophysiology. Tear secretion is controlled by the lacrimal functional unit consisting of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland and the interconnecting innervation. If any portion of this functional unit is compromised, lacrimal gland support to the ocular surface is impeded. Factors such as neurogenic inflammation and T cell involvement in the disease pathogenesis as well as newly developed animal models of ocular surface inflammation are discussed.

Lacrimal gland-derived IL-22 regulates IL-17-mediated ocular mucosal inflammation

PubMed Central

Ji, Yong Woo; Mittal, Sharad K.; Hwang, Ho Sik; Chang, Eun-Ju; Lee, Joon H.; Seo, Yuri; Yeo, Areum; Noh, Hyemi; Lee, Hye Sun; Chauhan, Sunil K.; Lee, Hyung Keun

2016-01-01

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. PMID:28051088

Biomaterials and Tissue Engineering Strategies for Conjunctival Reconstruction and Dry Eye Treatment

PubMed Central

Lu, Qiaozhi; Al-Sheikh, Osama; Elisseeff, Jennifer H.; Grant, Michael P.

2015-01-01

The ocular surface is a component of the anterior segment of the eye and is covered by the tear film. Together, they protect the vital external components of the eye from the environment. Injuries, surgical trauma, and autoimmune diseases can damage this system, and in severe cases, tissue engineering strategies are necessary to ensure proper wound healing and recovery. Dry eye is another major concern and a complicated disease affecting the ocular surface. More effective and innovative therapies are required for better outcomes in treating dry eye. This review focuses on the regenerative medicine of the conjunctiva, which is an essential part of the ocular surface system. Features and advances of different types of biomolecular materials, and autologous and allogeneic tissue grafts are summarized and compared. Specifically, vitrigel, a collagen membrane and novel material for use on the ocular surface, offers significant advantages over other biomaterials. This review also discusses a breakthrough microfluidic technology, “organ-on-a-chip” and its potential application in investigating new therapies for dry eye. PMID:26692712

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders.

PubMed

Nebbioso, Marcella; Del Regno, Paola; Gharbiya, Magda; Sacchetti, Marta; Plateroti, Rocco; Lambiase, Alessandro

2017-08-13

The tear film represents the interface between the eye and the environment. The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome. Despite having a multifactorial origin, the main risk factors are female gender and advanced age. Likewise, morphological changes in several glands and in the chemical composition of their secretions, such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors that maintain a steady ocular surface. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic inflammation that involves the ocular surface. DE syndrome is one of the most commonly encountered diseases in clinical practice, and many other causes related to daily life and the increase in average life expectancy will contribute to its onset. This review will consider the disorders of the ocular surface that give rise to such a widespread pathology. At the end, the most recent therapeutic options for the management of DE will be briefly discussed according to the specific underlying pathology.

Analysis of the Pathogenic Factors and Management of Dry Eye in Ocular Surface Disorders

PubMed Central

Del Regno, Paola; Sacchetti, Marta; Plateroti, Rocco

2017-01-01

The tear film represents the interface between the eye and the environment. The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome. Despite having a multifactorial origin, the main risk factors are female gender and advanced age. Likewise, morphological changes in several glands and in the chemical composition of their secretions, such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors that maintain a steady ocular surface. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic inflammation that involves the ocular surface. DE syndrome is one of the most commonly encountered diseases in clinical practice, and many other causes related to daily life and the increase in average life expectancy will contribute to its onset. This review will consider the disorders of the ocular surface that give rise to such a widespread pathology. At the end, the most recent therapeutic options for the management of DE will be briefly discussed according to the specific underlying pathology. PMID:28805710

Ocular findings in acquired immunodeficiency syndrome patients in Lagos, Nigeria.

PubMed

Onakoya, A O; Odeyemi, M G; Aribaba, O T; Akinsola, F B

2012-01-01

There is paucity of studies on the prevalence and pattern of ocular complication in HIV patients in developing countries where 90% of all HIV sufferers live. Most studies were carried out in industrialized countries and are not representative of the spectrum of ocular complication of HIV and it's prevalence in developing countries. To determine the prevalence of ocular disorders in adult (> 15 years ) AIDS patients at PEPFAR clinic in Lagos, Nigeria. All consecutive adult Seropositive HIV/AIDS patients of PEPFAR Clinic at the Lagos University Teaching Hospital between February 1st-March 15th 2008 were enrolled into the study Cross sectional and non randomized, convenient study was used. Biodata and medical history were recorded on interviewer administered questionnaire. Participants were examined according to standard protocol comprising visual acuity, intraocular pressure, anterior segment examination with slit lamp biomicroscopy, dilated fundoscopy and fundus photograph where necessary. PCV, CD4+ count, viral load at diagnosis, stage of HIV disease were extracted from patients' records. Details of drug were regimen also recorded. Data analysis was performed with EPI-lnfo 6.04 version; Chi square and student t test used to describe statistical association. A total of 400 patients were studied. Male:female ratio was 1.7 and mean age was 40 years (S.D. + 9.12). Ocular disorders seen in 78.5% of patients; HIV related ocular disorders occurred in 45 (11.3) patients. Conjunctival microvasculopathy 166 patients (41.5%), pingueculum in 114 (28.5%), pterygium in 76 (19.0%), refractive error in 93 (23.3%), cataract in 12 (3.0%), and 22 (5.5%) Glaucoma suspects. HIV retinopathy and allergic eye disease in one patient each (0.3%). Presumed Cytomegalovirus retinitis 7 (1.8%), 14 (3.5%) Toxoplasmosis, 8 (2.0%) HZO, and 15 (3.8%) Presumed Squamous cell carcinoma. Eighty six (21.5%) of the patients had no abnormality. 91.4% of eyes examined had visual acuity with best correction of > 6/18. CD4+ in 79.3% of the patients was > 200 cells/ul and < 5% had counts < 50 cells with an overall mean of 406 cell/ul. 375 (93.8%) patients were on Highly Active Antiretroviral therapy (HAART), and 25 (6.2%) were not. Study revealed low prevalence of HIV related ocular disorders. This could be due to few patients at low level of immunosuppresion where the infections occur.

Ocular surface and tear film status among contact lens wearers and non-wearers who use VDT at work: comparing three different lens types.

PubMed

Tauste, Ana; Ronda, Elena; Baste, Valborg; Bråtveit, Magne; Moen, Bente E; Seguí Crespo, María-Del-Mar

2018-04-01

To analyze differences in the ocular surface appearance and tear film status of contact lens wearers and non-wearers in a group of visual display terminals (VDT) workers and additionally to assess differences between lens materials. Cross-sectional study of 236 office workers, of whom 92 were contact lens wearers. Workers provided information on their contact lenses (conventional hydrogel, silicone hydrogel or rigid gas permeable lenses) and exposure to VDT at work. Ocular surface and tear film status were determined by the presence of bulbar, limbal and lid redness, lid roughness and corneal staining type, and by Schirmer's and tear break-up time tests (TBUT). A generalized linear model was used to calculate the crude (cRR) and age- and sex-adjusted (aRR) relative risk to measure the association between ocular surface and tear film abnormalities and contact lens use and type. The aRR of ocular surface abnormalities was higher in contact lens wearers compared to non-wearers: bulbar redness (aRR 1.69; 95% CI 1.25-2.30), limbal redness (aRR 2.87; 1.88-4.37), lid redness (aRR 2.53; 1.35-4.73) and lid roughness (aRR 7.03; 1.31-37.82). VDT exposure > 4 h/day increased wearers' risk of limbal and lid redness. Conventional hydrogel wearers had the highest risk of ocular surface abnormalities, followed by silicone hydrogel wearers. Both contact and non-contact lens wearers had a high prevalence of altered TBUT (77.3 and 75.7% respectively) and Schirmer (51.8 and 41.3%). Regular contact lens use during VDT exposure at work increases risk of bulbar, limbal and lid redness, and lid roughness, especially in soft contact lens wearers. The high prevalence of altered TBUT and Schirmer's results in all participants suggests that VDT use greatly affects tear film characteristics.

Cutaneous and laryngeal squamous cell carcinoma in mixed epidermolysis bullosa, kindler syndrome.

PubMed

Mizutani, Hiromi; Masuda, Koji; Nakamura, Naomi; Takenaka, Hideya; Tsuruta, Daisuke; Katoh, Norito

2012-05-01

Kindler syndrome is a rare autosomal recessive genodermatosis characterized by trauma-induced acral blisters in infancy and childhood, photosensitivity, and progressive poikiloderma. Other clinical features include chronic erosive gingivitis, dysphagia, esophageal and urethral strictures, ectropion, and an increased risk of mucocutaneous squamous cell carcinoma. We describe a patient with Kindler syndrome associated with squamous cell carcinoma of the skin and larynx. He had squamous cell carcinoma on his left knee with simultaneous unresectable laryngeal carcinoma at the age of 43 years. The squamous cell carcinoma on his knee was excised and the laryngeal carcinoma was treated with radiation therapy. Although pathophysiology of Kindler syndrome and its frequency of association with cancer are still not fully elucidated, we speculate that long-term erosion and regeneration of mucosal and cutaneous surfaces may have induced squamous cell carcinoma on the patient's knee and larynx.

Ocular surface alterations and in vivo confocal microscopic characteristics of corneas in patients with myasthenia gravis.

PubMed

Erkan Turan, Kadriye; Kocabeyoglu, Sibel; Bekircan-Kurt, Can Ebru; Bezci, Figen; Erdem-Ozdamar, Sevim; Irkec, Murat

2018-03-01

To evaluate ocular surface alterations and characteristics of corneal basal epithelium and subbasal nerves in patients with myasthenia gravis. Myasthenia gravis patients (n = 21) and healthy controls (n = 20) were enrolled. All participants underwent ocular surface testing in the following order: tear break-up time, lissamine green staining, Schirmer I test with anesthesia, and Ocular Surface Disease Index questionnaire. The Cochet-Bonnet esthesiometer was used to measure corneal sensitivity. Basal epithelial cells and subbasal nerves were evaluated using in vivo confocal microscopy. Myasthenia gravis patients had higher Ocular Surface Disease Index score (13.9 ± 15.0 vs 1.4 ± 2.2, p < 0.001) and lissamine green staining score (0.6 ± 0.4 vs 0.2 ± 0.4, p = 0.007). Break-up time score (9.3 ± 3.0 vs 9.9 ± 1.9, p = 0.481) and Schirmer I test score (16.5 ± 9.2 vs 19.3 ± 8.4, p = 0.323) did not differ significantly. Corneal sensation was 0.4 g/mm 2 in all eyes. Patients with myasthenia gravis had lower basal epithelial cell density (3775.7 ± 938.1 vs 4983.1 ± 608.5, p < 0.001) and total nerve density (1956.1 ± 373.3 vs 2277.9 ± 405.0, p = 0.012) and higher subbasal nerve tortuosity (1.9 ± 0.8 vs 1.6 ± 0.7, p = 0.007) than controls. A significant increase in Ocular Surface Disease Index scores was found with decreasing basal epithelial cell density (rho = -0.518, p = 0.001). There was a significantly moderate negative correlation between the duration of myasthenia gravis and the number of corneal nerves (rho = -0.497, p = 0.022). Significant alterations of basal epithelial cells and subbasal nerves were demonstrated in myasthenia gravis patients although there was no difference of corneal sensitivity between myasthenia gravis patients and healthy controls. Thus, it should be borne in mind that myasthenia gravis patients deserve further evaluation with regard to ocular surface disease.

Mucin gene expression is not regulated by estrogen and/or progesterone in the ocular surface epithelia of mice.

PubMed

Lange, Christine; Fernandez, Jolene; Shim, David; Spurr-Michaud, Sandra; Tisdale, Ann; Gipson, Ilene K

2003-07-01

Dry eye syndrome is prevalent in post-menopausal women, and post-menopausal women secrete less mucus in their reproductive tracts. Using a mouse model, the purpose of this study was to determine if estrogen and/or progesterone regulates Muc4 and Muc5AC gene expression in the ocular surface epithelia, as the hormones do in reproductive tract epithelia. Adult C57BL/6 mice were ovariectomized, and 19 days later, pellets containing estrogen, progesterone, or a combination were inserted subcutaneously. Ocular surface and reproductive tract tissues were harvested following seven days of hormone treatment. A control group consisted of ovariectomized mice that received no hormone treatment. Real-time reverse transcription-polymerase chain reaction was used to determine the tissue expression levels of mucin mRNA of each treatment group relative to the control. Muc4 mRNA expression levels were determined for the reproductive tract, and both Muc4 and Muc5AC expression levels were determined for the ocular surface epithelia. Muc4 and Muc5AC gene expression in ocular surface and Muc4 in reproductive tract epithelia was demonstrated by In Situ hybridization, and Muc4 and Muc5AC protein was demonstrated in the epithelia of animals in the experimental groups. The mRNA expression levels of Muc4 and Muc5AC and the immunofluorescence localization pattern in the ocular surface epithelia were not significantly different in any hormone treatment group when compared to the control ovariectomized group. By comparison, mice that were administered estrogen had a significant increase of Muc4 mRNA in the reproductive tract epithelia, progesterone given in combination with estrogen antagonized the upregulatory effects of estrogen in the reproductive tract, and the amount of Muc4 mRNA in the reproductive tract of progesterone-treated animals was not different from ovariectomized controls. Immunofluorescence localization of Muc4 in the reproductive tract epithelia of the experimental groups correlated to message levels, with lack of Muc4 protein detected in the control and progesterone groups. In comparison to reproductive tract epithelia, Muc4 and Muc5AC are not hormonally regulated by estrogen or progesterone in the ocular surface epithelia of mice. These data demonstrate that regulation of epithelial mucin genes is tissue specific.

Local synthesis of sex hormones: are there consequences for the ocular surface and dry eye?

PubMed

Gibson, Emma J; Stapleton, Fiona; Wolffsohn, James S; Golebiowski, Blanka

2017-12-01

Sex hormones are associated with the physiology and pathophysiology of almost all organs in the body, as well as most diseases. Interest in the associations between sex hormones and ocular tissues has increased in recent years. Androgens may have a positive effect on dry eye, whereas the effects of oestrogen on ocular conditions remain unclear. Intracrinology, the local synthesis and metabolism of hormones that is unique to humans, is of relevance to the eye and may help to explain why studies of the relationship between oestrogens and dry eye signs and symptoms are inconclusive. Knowledge of the pathways of hormone formation and metabolism is crucial to understanding the pathogenesis of ocular disease including dry eye. This review examines the mechanisms of steroidal sex hormone biosynthesis and reviews the significance of locally produced sex hormones, with a focus on ocular surface tissues. Much of the current literature is based on animal studies, which may not be transferable to humans due to the absence of intracrine production in animals. A large proportion of the human studies investigate systemic hormone levels rather than local levels. There is subsequently a need for additional studies to provide a better understanding of the local production of sex hormones within the human eye and ocular surface and to clarify the relationships between ocular levels of sex hormones and conditions including dry eye. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Preservative-free treatment in glaucoma: who, when, and why.

PubMed

Stalmans, Ingeborg; Sunaric Mégevand, Gordana; Cordeiro, M Francesca; Hommer, Anton; Rossetti, Luca; Goñi, Francisco; Heijl, Anders; Bron, Alain

2013-01-01

To review and summarize the available literature on the effect of preservatives on the eye, to provide practical guidance for the clinical assessment of the ocular surface in glaucoma patients, and to define patient populations that might benefit from preservative-free topical intraocular pressure (IOP)-lowering agents. This manuscript is based on a combination of a literature review on preservatives and the eye and expert opinion from glaucoma specialists with an interest in ocular surface disease. There is an increasingly recognized association between eyedrop preservatives and ocular surface disease. Preservative-free therapy is now available for a wide range of active compounds, although there are still some misconceptions regarding their appropriate use. For patients treated topically for glaucoma or ocular hypertension, a rough estimate could be that 20% may need treatment with topical IOP-reducing agents that are free from preservatives. This review provides an up-to-date account of the literature regarding preservatives and the eye, as well as suggestions and recommendations on to when to use preservative-free antiglaucoma treatment.

Therapeutic use of mini-scleral lenses in a patient with Graves' ophthalmopathy.

PubMed

Harthan, Jennifer S

2014-01-01

Patients with Graves' ophthalmopathy can be very challenging to manage secondary to the complex nature of their disease presentation. Patients may present with a variety of ocular findings including: lid retraction, periorbital and lid swelling, chemosis, conjunctival hyperemia, proptosis, optic neuropathy, restrictive myopathy, exposure keratopathy and/or keratoconjunctivitis sicca. Mini-scleral and scleral lens designs have been important in the management of irregular and regular corneas, and in the therapy of ocular surface diseases. We present here the case of a 48-year-old Caucasian male who had been diagnosed with Graves' ophthalmopathy 13 years earlier. With significant ocular surface staining and over ten diopters of astigmatism, the patient had never been able to wear contact lenses comfortably. After being fit with the Mini-Scleral Design™ lenses, his vision improved to 20/25 OU, his ocular surface improved, and overall quality of vision increased. Copyright © 2012 Spanish General Council of Optometry. Published by Elsevier Espana. All rights reserved.

Insects have hairy eyes that reduce particle deposition

NASA Astrophysics Data System (ADS)

Amador, G. J.; Durand, F.; Mao, W.; Pusulri, S.; Takahashi, H.; Nguyen, V.-T.; Shimoyama, I.; Alexeev, A.; Hu, D. L.

2015-12-01

An insect's eyes may make up to 40% of its body's surface, and are in danger of being coated by foreign particles such as dust and pollen. To protect them, several insect species possess an array of ocular hairs evenly spaced between each photoreceptor unit. Although these hairs have been observed for over 50 years, their purpose remains a mystery. In this study, we elucidate the function of ocular hairs using a combination of experiments, numerical simulation and micro-fabrication. We measure the eyes of 18 species of insects and find that the length of their ocular hairs is equal to their spacing. We conduct wind tunnel experiments using both an insect eye mimic and an at-scale fabricated micro-pillar array of the same dimensions as the insect eye. Our experiments and simulations show that ocular hairs reduce airflow at the eye surface by up to 90%. We conclude that ocular hairs act similarly to mammalian eyelashes: as insects fly, ocular hairs deflect incoming air and create a zone of stagnant air. Airflow and particle deposition are reduced dramatically, while light is only minimally occluded. Micro-scale ocular hairs may find application in the deployment of sensors outdoors, for which accumulation of airborne dust and pollen has no current solution.

A MODEL FOR THE TEAR FILM AND OCULAR SURFACE TEMPERATURE FOR PARTIAL BLINKS

PubMed Central

Deng, Quan; Braun, R. J.; Driscoll, T. A.; King-Smith, P. E.

2015-01-01

In this paper, we investigate the dynamics of tear film and the associated temperature variation for partial blinks. We investigate the mechanism of fluid supply during partial blink cycles, and compare the film thickness with observation in vivo. We find that varying the thickness of the fluid layer beneath the moving upper lid improves the agreement for the in vivo measurement of tear film thickness after a half blink. By examining the flux of the fluid, we provide an explanation of this assumption. We also investigate the temperature dynamics both at the ocular surface and inside the simulated anterior chamber. Our simulation results suggest that the ocular surface temperature readjusts rapidly to normal temperature distribution after partial blinks. PMID:25635242

Detection of sialomucin complex (MUC4) in human ocular surface epithelium and tear fluid.

PubMed

Pflugfelder, S C; Liu, Z; Monroy, D; Li, D Q; Carvajal, M E; Price-Schiavi, S A; Idris, N; Solomon, A; Perez, A; Carraway, K L

2000-05-01

To evaluate human ocular surface epithelium and tear fluid for the presence of sialomucin complex (MUC4), a high-molecular-weight heterodimeric glycoprotein composed of mucin (ASGP-1) and transmembrane (ASGP-2) subunits. Reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis assays were used to identify sialomucin complex RNA in ocular surface epithelia. Immunoprecipitation and immunoblot analysis were used to identify immunoreactive species in human tears and in the corneal and conjunctival epithelia using antibodies specific for carbohydrate and peptide epitopes on the sialomucin complex subunits. Immunofluorescence staining was used to detect sialomucin complex in frozen sections and impression cytology specimens of human cornea and conjunctival epithelia. ASGP-1- and ASGP-2-specific sequences were amplified from RNA extracted from both conjunctival and corneal epithelial biopsies by RT-PCR. Sialomucin complex transcripts were also detected in these tissues by Northern blot analysis, with a greater level of RNA detected in the peripheral than the central corneal epithelium. Sialomucin complex was immunoprecipitated from tear fluid samples and both corneal and conjunctival epithelia and detected by immunoblot analysis with specific anti-ASGP-1 and anti-ASGP-2 antibodies. The ASGP-1 peptide antibody HA-1 stained the full thickness of the corneal and conjunctival epithelia. In contrast, antibody 15H10, which reacts against a carbohydrate epitope on ASGP-1, stained only the superficial epithelial layers of these tissues. No staining was observed in the conjunctival goblet cells. Sialomucin complex was originally identified in rat mammary adenocarcinoma cells and has recently been shown to be produced by the ocular surface epithelia of rats. Furthermore, it has been identified as the rat homologue of human MUC4 mucin. The present studies show that it is expressed in the stratified epithelium covering the surface of the human eye and is present in human tear fluid. Expression of a carbohydrate-dependent epitope on the mucin subunit (ASGP-1) of sialomucin complex occurs in a differentiation-dependent fashion. Sialomucin complex joins MUC1 as another membrane mucin produced by the human ocular surface epithelia but is also found in the tear fluid, presumably in a soluble form, as found on the rat ocular surface.

Lacritin and other new proteins of the lacrimal functional unit.

PubMed

McKown, Robert L; Wang, Ningning; Raab, Ronald W; Karnati, Roy; Zhang, Yinghui; Williams, Patricia B; Laurie, Gordon W

2009-05-01

The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as 'an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them'. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over 200 new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin's low nanomolar mitogenic activity. The lacritin-binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction.

Ocular surface epithelium induces expression of human mucosal lymphocyte antigen (HML-1) on peripheral blood lymphocytes

PubMed Central

Gomes, J A P; Dua, H S; Rizzo, L V; Nishi, M; Joseph, A; Donoso, L A

2004-01-01

Background/aims: Peripheral blood CD8+ lymphocytes that home to mucosal surfaces express the human mucosal lymphocyte antigen (HML-1). At mucosal surfaces, including the ocular surface, only intraepithelial CD8+ lymphocytes express HML-1. These lymphocytes are retained in the intraepithelial compartment by virtue of the interaction between HML-1 and its natural ligand, E-cadherin, which is expressed on epithelial cells. The purpose of this study was to determine whether ocular surface epithelial cells (ocular mucosa) could induce the expression of human mucosal lymphocyte antigen on peripheral blood lymphocytes. Methods: Human corneal and conjunctival epithelial cells were co-cultured with peripheral blood lymphocytes. Both non-activated and activated lymphocytes were used in the experiments. After 7 days of incubation, lymphocytes were recovered and analysed for the antigens CD8/HML-1, CD4/HML-1, CD3/CD8, CD3/CD4, CD3/CD25, CD8/CD25, and CD4/CD25 by flowcytometry. Results: Significant statistical differences were observed in the CD8/HML-1 expression when conjunctival epithelial cells were co-cultured with non-activated and activated lymphocytes (p = 0.04 for each) and when corneal epithelial cells were co-cultured with non-activated lymphocytes (p = 0.03). Significant statistical difference in CD4/HML-1 expression was observed only when conjunctival epithelial cells were co-cultured with activated lymphocytes (p = 0.02). Conclusion: Ocular surface epithelial cells can induce the expression of human mucosal lymphocyte antigen on CD8+ (and to some extent on CD4+) lymphocytes. This may allow the retention of CD8+ and CD4+ lymphocytes within the epithelial compartment of the conjunctiva and play a part in mucosal homing of lymphocytes. PMID:14736792

Effect of 0.3% Hydroxypropyl Methylcellulose/Dextran Versus 0.18% Sodium Hyaluronate in the Treatment of Ocular Surface Disease in Glaucoma Patients: A Randomized, Double-Blind, and Controlled Study.

PubMed

Prabhasawat, Pinnita; Ruangvaravate, Ngamkae; Tesavibul, Nattaporn; Thewthong, Maneerat

2015-01-01

To compare the efficacy and safety of 0.3% hydroxypropyl methylcellulose/dextran (HPMC/dextran) and 0.18% sodium hyaluronate (SH) in the treatment of ocular surface disease in patients using antiglaucoma drugs containing preservatives. This was a double-blind, randomized, parallel-group study in 70 glaucoma patients with Ocular Surface Disease Index (OSDI) score greater than 20 points and/or presence of ocular signs. Patients were randomized to receive either preservative-free 0.3% HPMC/dextran (n=35) or preservative-free 0.18% SH (n=35). Treatment was 1 drop in each eye, 4 times a day. Data were collected at baseline, at day 7 and day 28. The groups were homogeneous at baseline. At day 28, both treatments showed significant improvements (P<0.05) in the mean OSDI score, lid skin and lid margin inflammation, conjunctival injection, and expressibility of meibomian glands, corneal staining score, fluorescein tear breakup time (FBUT), and Schirmer I test. However, the mean OSDI score, lid margin inflammation and conjunctival injection showed significant improvements (P<0.05) in the SH group at days 7 and 28, compared to the HPMC/dextran group. FBUT and the Schirmer I test also showed significant improvements (P<0.05) in the SH group compared to the HPMC/dextran group, at day 28. No adverse reactions were observed in either group. Preservative-free artificial tear, 0.3% HPMC/dextran, and 0.18% SH, caused a significant relief of the ocular surface disease in glaucoma patients. However, 0.18% SH led to a greater improvement in ocular signs and symptoms than 0.3% HPMC/dextran.

Rebamipide protects against glaucoma eyedrop-induced ocular surface disorders in rabbits

PubMed Central

Kawaguchi, Ichiro; Higashide, Tomomi; Takeji, Yasuhiro; Sakurai, Kazushi; Kawaguchi, Chiaki; Sugiyama, Kazuhisa

2017-01-01

Purpose This study aimed to determine if rebamipide eyedrops can improve ocular surface damage caused by the use of glaucoma eyedrops. Methods Female Kbl:Dutch rabbits were used to evaluate glaucoma eyedrop-induced ocular surface damage; one eye of each rabbit was untreated and the other was administered glaucoma eyedrops for 30 days. To evaluate the effects of rebamipide on ocular surface damage, one eye of each rabbit was administered vehicle-treated glaucoma eyedrops and the other was administered rebamipide-treated glaucoma eyedrops for 30 days. Corneal and conjunctival epithelial damage was evaluated using fluorescein and rose bengal staining, respectively. Conjunctival inflammation was observed by light microscopy with hematoxylin-eosin staining. Dark cells (in which the corneal microvilli were damaged) were analyzed by scanning electron microscopy. Results There were no significant differences in fluorescein staining between the untreated and glaucoma eyedrop-treated groups; however, rose bengal staining and the number of inflammatory cells in the conjunctiva significantly increased after glaucoma eyedrop treatment. There was a four-fold increase in the number of dark cells in the glaucoma eyedrop-treated group compared to untreated. In contrast, in the conjunctiva of the rebamipide-treated glaucoma eyedrop group, rose bengal staining scores, the number of inflammatory cells, and the number of dark cells were decreased compared to the vehicle-treated glaucoma eyedrop group. Conclusions Results from our in vivo rabbit study demonstrated that short-term use of glaucoma eyedrops induces corneal epithelium disorders at the cellular level, but that simultaneous use of rebamipide has the potential to protect and repair the ocular surface. PMID:29049370

Rebamipide protects against glaucoma eyedrop-induced ocular surface disorders in rabbits.

PubMed

Kawaguchi, Ichiro; Kobayashi, Akira; Higashide, Tomomi; Takeji, Yasuhiro; Sakurai, Kazushi; Kawaguchi, Chiaki; Sugiyama, Kazuhisa

2017-01-01

This study aimed to determine if rebamipide eyedrops can improve ocular surface damage caused by the use of glaucoma eyedrops. Female Kbl:Dutch rabbits were used to evaluate glaucoma eyedrop-induced ocular surface damage; one eye of each rabbit was untreated and the other was administered glaucoma eyedrops for 30 days. To evaluate the effects of rebamipide on ocular surface damage, one eye of each rabbit was administered vehicle-treated glaucoma eyedrops and the other was administered rebamipide-treated glaucoma eyedrops for 30 days. Corneal and conjunctival epithelial damage was evaluated using fluorescein and rose bengal staining, respectively. Conjunctival inflammation was observed by light microscopy with hematoxylin-eosin staining. Dark cells (in which the corneal microvilli were damaged) were analyzed by scanning electron microscopy. There were no significant differences in fluorescein staining between the untreated and glaucoma eyedrop-treated groups; however, rose bengal staining and the number of inflammatory cells in the conjunctiva significantly increased after glaucoma eyedrop treatment. There was a four-fold increase in the number of dark cells in the glaucoma eyedrop-treated group compared to untreated. In contrast, in the conjunctiva of the rebamipide-treated glaucoma eyedrop group, rose bengal staining scores, the number of inflammatory cells, and the number of dark cells were decreased compared to the vehicle-treated glaucoma eyedrop group. Results from our in vivo rabbit study demonstrated that short-term use of glaucoma eyedrops induces corneal epithelium disorders at the cellular level, but that simultaneous use of rebamipide has the potential to protect and repair the ocular surface.

Tear Osmolarity and Correlation With Ocular Surface Parameters in Patients With Dry Eye.

PubMed

Mathews, Priya M; Karakus, Sezen; Agrawal, Devika; Hindman, Holly B; Ramulu, Pradeep Y; Akpek, Esen K

2017-11-01

To analyze the distribution of tear film osmolarity in patients with dry eye and its association with other ocular surface parameters. Tear osmolarity and other quantitative dry eye parameters were obtained from patients with 1) clinically significant dry eye (significant symptoms and ocular surface staining, n = 131), 2) symptoms-only dry eye (significant symptoms but no significant ocular surface staining, n = 52), and 3) controls (no significant symptoms or staining, n = 42). Tear osmolarity varied significantly across groups (P = 0.01), with patients with clinically significant dry eye having the highest tear osmolarity (312.0 ± 16.9 mOsm/L), control patients having the lowest tear osmolarity (305.6 ± 9.7 mOsm/L), and patients with symptoms-only dry eye falling in between (307.4 ± 5.6 mOsm/L). Patients with clinically significant dry eye also tended to have a greater intereye difference in osmolarity (12.0 ± 13.4) than did the individuals with symptoms-only dry eye (9.1 ± 12.4) and controls (9.0 ± 7.4) (P = 0.06). In multivariable regression models, higher tear osmolarity was associated with higher Ocular Surface Disease Index, discomfort subscore (P = 0.02), and higher corneal and conjunctival staining scores (P < 0.01 for both). Worse eye tear osmolarity was not correlated with the corresponding tear film breakup time or Schirmer test (P > 0.05 for both). Individuals with symptomatic dry eye that is not yet clinically significant seem to have higher and more variable osmolarity measurements than controls, potentially indicating that changes in osmolarity precede clinical findings.

[Optimization of benzalkonium chloride concentration in 0.0015% tafluprost ophthalmic solution from the points of ocular surface safety and preservative efficacy].

PubMed

Asada, Hiroyuki; Takaoka-Shichijo, Yuko; Nakamura, Masatsugu; Kimura, Akio

2010-06-01

Optimization of benzalkonium chloride (alkyl dimethylbenzylammonium chloride: BAK) concentration as preservative in 0.0015% tafluprost ophthalmic solution (Tapros 0.0015% ophthalmic solution), an anti-glaucoma medicine, was examined from the points of ocular surface safety and preservative efficacy. BAKC(12), which is dodecyl dimethylbenzylammonium chloride, and BAKmix, which is the mixture of dodecyl, tetradecyl and hexadecyl dimethylbenzylammonium chloride were used in this study. The effects of BAKC(12) concentrations and the BAK types, BAKC(12) and BAKmix, in tafluprost ophthalmic solution on ocular surface safety were evaluated using the in vitro SV 40-immobilized human corneal epithelium cell line (HCE-T). Following treatments of Tafluprost ophthalmic solutions with BAKC(12), its concentration dependency was observed on cell viability of HCE-T. The cell viability of HCE-T after treatment of these solutions with 0.001% to 0.003% BAKC(12) for 5 minutes were the same level as that after treatment of the solution without BAK. Tafluprost ophthalmic solution with 0.01% BAKC(12) was safer for the ocular surface than the same solution with 0.01% BAKmix. Preservatives-effectiveness tests of tafluprost ophthalmic solutions with various concentrations of BAKC(12) were performed according to the Japanese Pharmacopoeia (JP), and solutions with more than 0.0005% BAKC(12) conformed to JP criteria. It was concluded that 0.0005% to 0.003% of BAKC(12) in tafluprost ophthalmic solution was optimal, namely, well-balanced from the points of ocular surface safety and preservative efficacy.

Anterior Corneal, Posterior Corneal, and Lenticular Contributions to Ocular Aberrations.

PubMed

Atchison, David A; Suheimat, Marwan; Mathur, Ankit; Lister, Lucas J; Rozema, Jos

2016-10-01

To determine the corneal surfaces and lens contributions to ocular aberrations. There were 61 healthy participants with ages ranging from 20 to 55 years and refractions -8.25 diopters (D) to +3.25 D. Anterior and posterior corneal topographies were obtained with an Oculus Pentacam, and ocular aberrations were obtained with an iTrace aberrometer. Raytracing through models of corneas provided total corneal and surface component aberrations for 5-mm-diameter pupils. Lenticular contributions were given as differences between ocular and corneal aberrations. Theoretical raytracing investigated influence of object distance on aberrations. Apart from defocus, the highest aberration coefficients were horizontal astigmatism, horizontal coma, and spherical aberration. Most correlations between lenticular and ocular parameters were positive and significant, with compensation of total corneal aberrations by lenticular aberrations for 5/12 coefficients. Anterior corneal aberrations were approximately three times higher than posterior corneal aberrations and usually had opposite signs. Corneal topographic centers were displaced from aberrometer pupil centers by 0.32 ± 0.19 mm nasally and 0.02 ± 0.16 mm inferiorly; disregarding corneal decentration relative to pupil center was significant for oblique astigmatism, horizontal coma, and horizontal trefoil. An object at infinity, rather than at the image in the anterior cornea, gave incorrect aberration estimates of the posterior cornea. Corneal and lenticular aberration magnitudes are similar, and aberrations of the anterior corneal surface are approximately three times those of the posterior surface. Corneal decentration relative to pupil center has significant effects on oblique astigmatism, horizontal coma, and horizontal trefoil. When estimating component aberrations, it is important to use correct object/image conjugates and heights at surfaces.

Topically applied 1% voriconazole induces dysplastic changes on the ocular surface: animal study.

PubMed

Arikan, Gul; Karatas, Ezgi; Lebe, Banu; Ayhan, Ziya; Utine, Canan Asli; Kutsoylu, Oya Eren; Gunenc, Uzeyir; Yilmaz, Osman

2018-04-26

To identify the risk of inducing ocular surface dysplasia following topical administration of 1% voriconazole eye drop. Fourteen noninflamed healthy eyes of 14 white adult New Zealand rabbits were included in the study. The rabbits were randomly divided into two groups comprised of 7 rabbits each. Group 1 received topical 1% voriconazole and Group 2 received topical saline as the control group. In all animals, right eye was selected for the study. In Group 1 (Voriconazole Group), single drop of voriconazole was instilled every 10 min consecutively for 17 times a day for 60 days. In Group 2 (Control Group), single drop of saline was instilled every 10 min consecutively for 17 times a day for 60 days. At two months, animals were sacrificed and study eyes were enucleated with the eyelids. The specimens were stained with hematoxylin-eosin and histopathologic changes in cornea, bulbar and palpebral conjunctiva were evaluated under light microscope. There were no macroscopically visible lesions on the ocular surface of any rabbits. Histopathological evaluation showed mild to moderate dysplasia localized mainly in the limbus and extending to the adjacent cornea and bulbar conjunctiva in all rabbits in Voriconazole Group. Severe dysplasia or carcinoma in situ was not observed. In the Control Group, dysplasia was not observed, at all. This animal study provides a possible relationship between topically administered 1% voriconazole and ocular surface dysplasia. We recommend ophthalmologists to be aware of the risk of ocular surface dysplasia in patients received voriconazole eye drop.

Relevance of Lipid-Based Products in the Management of Dry Eye Disease.

PubMed

Garrigue, Jean-Sébastien; Amrane, Mourad; Faure, Marie-Odile; Holopainen, Juha M; Tong, Louis

2017-11-01

Components of the ocular surface synergistically contribute to maintaining and protecting a smooth refractive layer to facilitate the optimal transmission of light. At the air-water interface, the tear film lipid layer (TFLL), a mixture of lipids and proteins, plays a key role in tear surface tension and is important for the physiological hydration of the ocular surface and for ocular homeostasis. Alterations in tear fluid rheology, differences in lipid composition, or downregulation of specific tear proteins are found in most types of ocular surface disease, including dry eye disease (DED). Artificial tears have long been a first line of treatment in DED and aim to replace or supplement tears. More recently, lipid-containing eye drops have been developed to more closely mimic the combination of aqueous and lipid layers of the TFLL. Over the last 2 decades, our understanding of the nature and importance of lipids in the tear film in health and disease has increased substantially. The aim of this article is to provide a brief overview of our current understanding of tear film properties and review the effectiveness of lipid-based products in the treatment of DED. Liposome lid sprays, emulsion eye drops, and other lipid-containing formulations are discussed.

Thermal fluctuation based study of aqueous deficient dry eyes by non-invasive thermal imaging.

PubMed

Azharuddin, Mohammad; Bera, Sumanta Kr; Datta, Himadri; Dasgupta, Anjan Kr

2014-03-01

In this paper we have studied the thermal fluctuation patterns occurring at the ocular surface of the left and right eyes for aqueous deficient dry eye (ADDE) patients and control subjects by thermal imaging. We conducted our experiment on 42 patients (84 eyes) with aqueous deficient dry eyes and compared with 36 healthy volunteers (72 eyes) without any history of ocular surface disorder. Schirmer's test, Tear Break-up Time, tear Meniscus height and fluorescein staining tests were conducted. Ocular surface temperature measurement was done, using an FL-IR thermal camera and thermal fluctuation in left and right eyes was calculated and analyzed using MATLAB. The time series containing the sum of squares of the temperature fluctuation on the ocular surface were compared for aqueous deficient dry eye and control subjects. Significant statistical difference between the fluctuation patterns for control and ADDE was observed (p < 0.001 at 95% confidence interval). Thermal fluctuations in left and right eyes are significantly correlated in controls but not in ADDE subjects. The possible origin of such correlation in control and lack of correlation in the ADDE subjects is discussed in the text. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of Dry Eye and Meibomian Gland Dysfunction in Teenagers with Myopia through Noninvasive Keratograph

PubMed Central

Wang, Xiu; Lu, Xiaoxiao; Yang, Jun; Wei, Ruihua; Yang, Liyuan; Zhao, Shaozhen; Wang, Xilian

2016-01-01

Purpose. This study aims to evaluate dry eye and ocular surface conditions of myopic teenagers by using questionnaire and clinical examinations. Methods. A total of 496 eyes from 248 myopic teenagers (7–18 years old) were studied. We administered Ocular Surface Disease Index (OSDI) questionnaire, slit-lamp examination, and Keratograph 5M. The patients were divided into 2 groups based on OSDI dry eye standard, and their ocular surfaces and meibomian gland conditions were evaluated. Results. The tear meniscus heights of the dry eye and normal groups were in normal range. Corneal fluorescein scores were significantly higher whereas noninvasive break-up time was dramatically shorter in the dry eye group than in the normal group. All three meibomian gland dysfunction parameters (i.e., meibomian gland orifice scores, meibomian gland secretion scores, and meibomian gland dropout scores) of the dry eye group were significantly higher than those of the normal group (P < 0.0001). Conclusions. The prevalence of dry eye in myopic teenagers is 18.95%. Meibomian gland dysfunction plays an important role in dry eye in myopic teenagers. The Keratograph 5M appears to provide an effective noninvasive method for assessing ocular surface situation of myopic teenagers. PMID:26881059

Changes in the tear film and ocular surface from dry eye syndrome.

PubMed

Johnson, Michael E; Murphy, Paul J

2004-07-01

Dry eye syndrome (DES) refers to a spectrum of ocular surface diseases with diverse and frequently multiple aetiologies. The common feature of the various manifestations of DES is an abnormal tear film. Tear film abnormalities associated with DES are tear deficiency, owing to insufficient supply or excessive loss, and anomalous tear composition. These categorizations are artificial, as in reality both often coexist. DES disrupts the homeostasis of the tear film with its adjacent structures, and adversely affects its ability to perform essential functions such as supporting the ocular surface epithelium and preventing microbial invasion. In addition, whatever the initial trigger, moderate and severe DES is characterized by ocular surface inflammation, which in turn becomes the cause and consequence of cell damage, creating a self-perpetuating cycle of deterioration. Progress has been made in our understanding of the aetiology and pathogenesis of DES, and these advances have encouraged a proliferation of therapeutic options. This article aims to amalgamate prevailing ideas of DES development, and to assist in that, relevant aspects of the structure, function, and production of the tear film are reviewed. Additionally, a synopsis of therapeutic strategies for DES is presented, detailing treatments currently available, and those in development.

Improved impression cytology techniques for the immunopathological diagnosis of superficial viral infections

PubMed Central

Thiel, M; Bossart, W; Bernauer, W

1997-01-01

BACKGROUND—For epidemiological and therapeutic reasons early diagnosis of superficial viral infections is crucial. Conventional microbiological techniques are expensive, time consuming, and not sufficiently sensitive. In this study impression cytology techniques were evaluated to analyse their diagnostic potential in viral infections of the ocular surface.
METHOD—A Biopore membrane device instead of the original impression cytology technique was used to allow better quality and handling of the specimens. The impressions were processed, using monoclonal antibodies and immunoperoxidase or immunofluorescence techniques to assess the presence of herpes simplex virus, varicella zoster virus, or adenovirus antigens. Ocular surface specimens from healthy individuals (n=10) and from patients with suspected viral surface disease (n=19) were studied. Infected and non-infected cell cultures served as controls.
RESULTS—This modified technique of impression cytology allowed the collection of large conjunctival and corneal epithelial cell layers with excellent morphology. Immunocytological staining of these samples provided diagnostic results for all three viruses in patients with viral surface disease.
CONCLUSIONS—The use of Biopore membrane devices for the collection of ocular surface epithelia offers new diagnostic possibilities for external eye diseases. Immunopathological methods that are applied directly on these membrane devices can provide virological results within 1-4 hours. This contributes considerably to the clinical management of patients with infectious diseases of the ocular surface.

 PMID:9505824

Tear film aberration dynamics and vision-related quality of life in patients with dry eye disease.

PubMed

Denoyer, Alexandre; Rabut, Ghislaine; Baudouin, Christophe

2012-09-01

Corneal and ocular wavefront aberrations were recorded together with clinical examination results and patient-reported vision-related quality-of-life evaluation results to define the relevance of dynamic optical analysis of the eye in dry eye disease (DED). Prospective and comparative clinical study. Forty DED patients and 40 age- and gender-matched control subjects. Serial measurements of ocular and corneal higher-order aberrations (HOAs) after blink were performed for 10 seconds using the KR-1 aberrometer (Topcon, Clichy, France). Vision-related health-targeted quality of life was evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. The clinical examination included tear film assessment (tear film break-up time and Schirmer I test), ocular surface damage assessment with the Oxford and van Bijsterveld indexes, and Meibomian dysfunction grading. Tear osmolarity also was measured. The time course of HOAs and modulation transfer function (MTF) was compared between groups and was analyzed in comparison with the OSDI and clinical data in DED patients. The root mean square of ocular and corneal total HOAs, particularly third-order aberrations, significantly increased over the 10-second period in DED patients, whereas no change occurred in controls. Analysis of MTF revealed progressive degradation of ocular optical quality resulting from loss of contrast at intermediate and high spatial frequencies in DED patients compared with controls. The progression index for corneal HOAs was correlated with the subjective index of patient-reported visual outcomes and with objective clinical findings of tear film and ocular surface damage. Objective measurement of the time course of HOAs may constitute a new single instrument to evaluate and manage patients with DED because it reliably reflects the completeness of the disease. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Eye cosmetic usage and associated ocular comfort.

PubMed

Ng, Alison; Evans, Katharine; North, Rachel; Purslow, Christine

2012-11-01

Eye cosmetics usage is commonplace and whilst some products such as eyeliner are applied with close proximity to the ocular surface, there is little knowledge of the short- and long-term ocular effects of eye cosmetic formulations. This study aimed to investigate the use of eye cosmetics and identify any relationships between ocular comfort and cosmetic usage. Results were collated from an online survey comprising 23 questions that recorded demographics, Ocular Surface Disease Index (OSDI) score, extent and range of eye cosmetic use and perceived comfort differences with and without eye cosmetics. The 1360 female respondents (median age 25, interquartile range 20-34 years) completed the survey; 83% reported using eye cosmetics regularly (≥ 3 times per week) with mascara being most commonly used. Fifty three per cent used at least three different eye cosmetics products regularly. OSDI scores of cosmetics users were similar to non-users (p = 0.083), but perceived comfort was greater when cosmetics were not used (p < 0.001). In occasional cosmetics users (use of products < 3 times per week), 65% reported a reduction in comfort when cosmetics were used. Median OSDI scores suggested a trend towards reduced comfort amongst eyeliner users (p = 0.07) although frequency and type of cosmetic products used did not appear to influence OSDI scores. This study shows the use of multiple eye cosmetics is extensive and associated with the perception of ocular discomfort. With such widespread use of these products, more research is required to assess the effect on the ocular surface and tear film, which may be underestimated. Ophthalmic & Physiological Optics © 2012 The College of Optometrists.

The Effect of Tear Supplementation with 0.15% Preservative-Free Zinc-Hyaluronate on Ocular Surface Sensations in Patients with Dry Eye.

PubMed

Perényi, Kristóf; Dienes, Lóránt; Kornafeld, Anna; Kovács, Balázs; Kiss, Huba J; Szepessy, Zsuzsanna; Nagy, Zoltán Z; Barsi, Árpád; Acosta, M Carmen; Gallar, Juana; Kovács, Illés

To evaluate the effect of tear supplementation with preservative free 0.15% zinc-hyaluronate on ocular surface sensations and corneal sensitivity in dry eye patients. Ocular surface sensations were assessed using the ocular surface disease index (OSDI) questionnaire and by recording ocular sensations during forced blinking in parallel with noninvasive tear film breakup time measurement in 20 eyes of 20 dry eye patients. Corneal sensitivity thresholds to selective stimulation of corneal mechano-, thermal- and chemical receptors were measured using the Belmonte gas esthesiometer. All baseline measurements were repeated after 1 month of treatment with 0.15% zinc-hyaluronate. After 1 month, a significant decrease in mean OSDI score (from 35.66 ± 12.36 to 15.03 ± 11.22; P < 0.001) and a significant improvement in tear film breakup time (from 3.83 ± 0.80 to 8.67 ± 4.50 s; P < 0.001) was observed compared to baseline. Sensory responses during the interblink period also significantly decreased after 1 month (P < 0.004). Corneal sensitivity thresholds to mechanical stimulation (90.61 ± 20.35 vs. 103.92 ± 17.97 mL/min; P < 0.025) and chemical stimulation (33.21 ± 0.51 vs. 33.58% ± 0.44% CO 2 ; P < 0.025) significantly increased after 1 month, however sensitivity thresholds to thermal stimulation remained unchanged compared to baseline (P > 0.05). Prolonged use of 0.15% zinc-hyaluronate results in an improvement of tear film stability and a decrease of dry eye complaints. The decrease in corneal mechano-and polymodal receptor excitability suggests that zinc-hyaluronate helps to recover normal corneal sensitivity, and thus might have a beneficial additional effect on reducing ocular surface complaints in dry eye patients.

Mucins in contact lens wear and dry eye conditions.

PubMed

Ramamoorthy, Padmapriya; Nichols, Jason J

2008-08-01

Ocular mucins are thought to play integral roles in ocular surface lubrication, anchoring of the aqueous, stabilizing the lipid components of the tear film, eliminating foreign bodies and pathogens, and with potential involvement in cell cycle mediation and apoptotic activity of ocular surface epithelia. Ocular mucins are of secreted and membrane-associated types. Secreted mucins may be of large gel-forming type or small soluble mucins (e.g., MUC5AC and MUC7). Membrane-associated mucins such as MUCs 1 and 4 are a major component of the glycocalyx. They are thought to render structural support to the microplicae and mediate epithelial cell cycle and apoptotic activity. The alterations in ocular mucins with contact lens wear are unclear. Recent work shows mucin expression may be up-regulated during the early years of contact lens wear, and with long-term lens wear, mucin expression may return to normal levels or sub-normal levels, although this is not well understood. Further, the polar nature of mucins may be associated with their affinity for contact lens surfaces making them a component of contact lens deposition. This has potential implications in the wettability and tolerability of contact lenses, and may be impacted by surface coatings, polymer characteristics, or care solutions. Conjunctival mucin gene expression and secretion may be deficient in several ocular surface disorders associated with dry eye. Deficiency and alterations in glycosylation characteristics of MUC5AC and MUC2 have been reported in both Sjögren and non-Sjögren dry eye types. Decreased binding of the membrane-associated mucin MUC16 to the conjunctival epithelium has been reported in Sjögren dry eye while MUC1 alterations have been reported in Sjögren and non-Sjögren dry eye states. In view of the mucin involvement in dry eye conditions, stimulation of mucus secretion pathways may hold promise in the pharmaceutical treatment of dry eye.

Management of patients with ocular manifestations in vesiculobullous disorders affecting the mouth.

PubMed

Hansen, M S; Klefter, O N; Julian, H O; Lynge Pedersen, A M; Heegaard, S

2017-10-01

Pemphigoid and pemphigus diseases as well as Stevens-Johnson syndrome present as vesiculobullous disorders of the skin and may additionally involve both the oral cavity and the ocular surface. Ocular involvement ranges from mild irritation and dry eye disease to chronic conjunctivitis, symblepharon, eyelid malposition, ocular surface scarring and severe visual loss. In addition to diagnostic assessments, ophthalmologists must treat the dry eye and meibomian gland dysfunction components of these diseases using a stepladder approach, including eyelid hygiene and lubricants. Topical anti-inflammatory therapy is used to treat acute inflammatory exacerbations of the ocular surface, but it cannot prevent scarring alone. Intralesional antimetabolite therapy can cause regression of conjunctival pathology in selected cases. Hence, patients with vesiculobullous disorders should be managed by a multidisciplinary team representing ophthalmology, dermatology, otolaryngology, oral medicine and pathology, internal medicine and intensive care. Systemic treatments including corticosteroids, azathioprine, cyclophosphamide, cyclosporine and mycophenolate mofetil help control inflammation. Intravenous immunoglobulins, plasmapheresis and targeted antibody therapy can be used in selected, severe and treatment-resistant cases. Local surgical management may include debridement of pseudomembranes, lysis of symblepharon, amniotic and mucous membrane grafting as well as reconstructive procedures. Prospective, multicentre, international studies are recommended to further support evidence-based practice. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Infection and Replication of Influenza Virus at the Ocular Surface.

PubMed

Creager, Hannah M; Kumar, Amrita; Zeng, Hui; Maines, Taronna R; Tumpey, Terrence M; Belser, Jessica A

2018-04-01

Although influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work has shown that isolates of multiple subtypes from both ocular and respiratory infections are capable of replication in human ex vivo ocular tissues and corneal or conjunctival cell monolayers, leaving the determinants of ocular tropism unclear. Here, we evaluated the effect of several variables on tropism for ocular cells cultured in vitro and examined the potential effect of the tear film on viral infectivity. All viruses tested were able to replicate in primary human corneal epithelial cell monolayers subjected to aerosol inoculation. The temperature at which cells were cultured postinoculation minimally affected infectivity. Replication efficiency, in contrast, was reduced at 33°C relative to that at 37°C, and this effect was slightly greater for the conjunctivitis isolates than for the respiratory ones. With the exception of a seasonal H3N2 virus, the subset of viruses studied in multilayer corneal tissue constructs also replicated productively after either aerosol or liquid inoculation. Human tears significantly inhibited the hemagglutination of both ocular and nonocular isolates, but the effect on viral infectivity was more variable, with tears reducing the infectivity of nonocular isolates more than ocular isolates. These data suggest that most influenza viruses may be capable of establishing infection if they reach the surface of ocular cells but that this is more likely for ocular-tropic viruses, as they are better able to maintain their infectivity during passage through the tear film. IMPORTANCE The potential spread of zoonotic influenza viruses to humans represents an important threat to public health. Unfortunately, despite the importance of cellular and tissue tropism to pathogenesis, determinants of influenza virus tropism have yet to be fully elucidated. Here, we sought to identify factors that limit the ability of most influenza viruses to cause ocular infection. Although ocular symptoms in humans caused by avian influenza viruses tend to be relatively mild, these infections are concerning due to the potential of the ocular surface to serve as a portal of entry for viruses that go on to establish respiratory infections. Furthermore, a better understanding of the factors that influence infection and replication in this noncanonical site may point toward novel determinants of tropism in the respiratory tract. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Oculoplastic technique of connecting a glaucoma valve shunt to extraorbital locations in cases of severe glaucoma.

PubMed

Rubin, Peter A D; Chang, Eli; Bernardino, Carlo Roberto; Hatton, Mark P; Dohlman, Claes H

2004-09-01

To describe a technique for inserting glaucoma shunts to the sinuses or the lacrimal sac as a means of lowering intraocular pressure in patients with refractory glaucoma associated with severe ocular surface disease. Nineteen patients with severe ocular surface disease necessitating a keratoprosthesis and with intractable glaucoma underwent placement of a modified Ahmed shunt to direct aqueous in the maxillary or ethmoid sinus or lacrimal sac. Intraocular pressure is presently well controlled without glaucoma medications in two thirds of patients. None of the patients had endophthalmitis. Established oculoplastic surgery techniques may be used to redirect aqueous to extraorbital locations and effectively lower intraocular pressure in patients with severe ocular surface disease and refractory glaucoma. This procedure has not been associated with endophthalmitis.

Recent developments on dry eye disease treatment compounds.

PubMed

Colligris, Basilio; Alkozi, Hanan Awad; Pintor, Jesus

2014-01-01

Dry eye syndrome is a common tears and ocular surface multifactorial disease, described by changes in the ocular surface epithelia related to reduced tears quantity and ocular surface sensitivity, leading to inflammatory reaction. Managing the eye inflammation proved helpful to patients with dry eye disease and current treatment is based on the use of topically applied artificial tear products/lubricants, tear retention management, stimulation of tear secretion and using anti-inflammatory drugs. In this article we revise the corresponding literature and patents assembling the new treatment approaches of novel and future pharmaceutical compounds destined for the dry eye disease treatment. The most frequent categories of compounds presented are secretagogues and anti-inflammatory drugs. These compounds are the research outcome of novel therapeutic strategies designed to reduce key inflammatory pathways and restore healthy tear film.

Periocular Reconstruction in Patients with Facial Paralysis.

PubMed

Joseph, Shannon S; Joseph, Andrew W; Douglas, Raymond S; Massry, Guy G

2016-04-01

Facial paralysis can result in serious ocular consequences. All patients with orbicularis oculi weakness in the setting of facial nerve injury should undergo a thorough ophthalmologic evaluation. The main goal of management in these patients is to protect the ocular surface and preserve visual function. Patients with expected recovery of facial nerve function may only require temporary and conservative measures to protect the ocular surface. Patients with prolonged or unlikely recovery of facial nerve function benefit from surgical rehabilitation of the periorbital complex. Current reconstructive procedures are most commonly intended to improve coverage of the eye but cannot restore blink. Copyright © 2016 Elsevier Inc. All rights reserved.

Ocular surface involvements in ectrodactyly-ectodermal dysplasia-cleft syndrome.

PubMed

Kennedy, David P; Chandler, John W; McCulley, James P

2015-06-01

To present the ocular manifestation of 2 cases of ectrodactyly-ectodermal dysplasia-cleft syndrome, a multiple congenital anomaly syndrome caused by a single point mutation of the p63 gene that controls epidermal development and homeostasis and to present treatment options. Patient 1 presented with mild signs and symptoms of dry eye and limbal stem cell deficiency with retention of 20/30 vision. Patient 2 presented with severe signs and symptoms of limbal stem cell deficiency with diffuse corneal scarring and counting fingers vision. This second patient's course was complicated by allergic conjunctivitis and advanced steroid-induced glaucoma. The cause of visual loss in ectrodactyly-ectodermal dysplasia-cleft syndrome appears to be multifactorial and likely includes inflammation of the ocular surface, tear film abnormalities, eyelid abnormalities, and limbal stem cell deficiency. Treatment modalities including lubrication, contact lenses, and limbal stem cell transplantation are reviewed. The ophthalmic conditions seen in ectrodactyly-ectodermal dysplasia-cleft syndrome frequently lead to vision loss. Early correct diagnosis and appropriate therapy are paramount because p63 gene mutations have a critical role in maintaining the integrity of the ocular surface in the setting of limbal stem cell deficiency, especially if there are other ocular surface insults such as lid disease, meibomian gland dysfunction and toxicity from topical medications. Patients should be monitored at regular, frequent intervals; and particular attention should be taken to avoid adverse secondary effects of these conditions and medications. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Exploring topical anti-glaucoma medication effects on the ocular surface in the context of the current understanding of dry eye.

PubMed

Wong, Aaron B C; Wang, Michael T M; Liu, Kevin; Prime, Zak J; Danesh-Meyer, Helen V; Craig, Jennifer P

2018-07-01

To assess tear film parameters, ocular surface characteristics, and dry eye symptomology in patients receiving topical anti-glaucoma medications. Thirty-three patients with a diagnosis of open angle glaucoma or ocular hypertension, receiving unilateral topical anti-glaucoma medication for at least 6 months, were recruited in a cross-sectional, investigator-masked, paired-eye comparison study. Tear film parameters, ocular surface characteristics, and dry eye symptomology of treated and fellow eyes were evaluated and compared. The mean ± SD age of the participants was 67 ± 12 years, and the mean ± SD treatment duration was 5.3 ± 4.4 years. Treated eyes had poorer non-invasive tear film breakup time (p = 0.03), tear film osmolarity (p = 0.04), bulbar conjunctival hyperaemia (p = 0.04), eyelid margin abnormality grade (p = 0.01), tear meniscus height (p = 0.03), and anaesthetised Schirmer value (p = 0.04) than fellow eyes. There were no significant differences in dry eye symptomology, meibomian gland assessments, and ocular surface staining between treated and fellow eyes (all p > 0.05). Adverse changes in tear film stability, tear osmolarity, conjunctival hyperaemia, and eyelid margins were observed in treated eyes. This suggests that inflammatory mechanisms may be implicated in the development of dry eye in patients receiving long term topical anti-glaucoma therapy. Copyright © 2018 Elsevier Inc. All rights reserved.

Impairment of vascularization of the surface covering epithelium induces ischemia and promotes malignization: a new hypothesis of a possible mechanism of cancer pathogenesis.

PubMed

Karseladze, A I

2015-06-01

To study the peculiarities of vascularization at the stromal-epithelial interface in different types of epithelia and their alterations in precancerous lesions. Peritumoral tissues of 310 patients, tissues of 180 healthy persons and of 50 human embryos and fetuses were used. Traditional histological as well as immunohistochemical methods have been used. The study reveals that the occurrence of blood capillaries in surface squamous epithelium is an ordinary event, both in healthy persons and in peritumoral regions of the patients with squamous cell carcinoma. Glandular epithelial coverings, as well as transitional epithelium, do not contain blood vessels. In squamous epithelium, only basal cells are in contact with the membrane and underlying stroma, the cells of the upper layer receiving nutrients through diffusion. Thus, the cells of squamous epithelium are more vulnerable to blood deficiency, since for instance in the pseudo-multilayered respiratory epithelium each cell is attached directly to the basal membrane and has more ample access to the blood supply. Metaplastic squamous epithelium has a markedly reduced vascularization and seems to be more sensitive to carcinogenic stimuli. High-grade dysplastic squamous epithelium and carcinoma in situ do not contain blood vessels. The process of redistribution of vascular network occurring at the interface of epithelial-stromal frontier plays an important role in maintaining the adequate metabolism of cells including those of epithelial covering. Impairment of this mechanism most probably promotes precancerous alterations.

Application of Hydrogel Template Strategy in Ocular Drug Delivery.

PubMed

Shin, Crystal S; Marcano, Daniela C; Park, Kinam; Acharya, Ghanashyam

2017-01-01

The hydrogel template strategy was previously developed to fabricate homogeneous polymeric microparticles. Here, we demonstrate the versatility of the hydrogel template strategy for the development of nanowafer-based ocular drug delivery systems. We describe the fabrication of dexamethasone-loaded nanowafers using polyvinyl alcohol and the instillation of a nanowafer on a mouse eye. The nanowafer, a small circular disk, is placed on the ocular surface, and it releases a drug as it slowly dissolves over time, thus increasing ocular bioavailability and enhancing efficiency to treat eye injuries.

Ocular Pharmacology of Tear Film, Dry Eye, and Allergic Conjunctivitis.

PubMed

Gulati, Shilpa; Jain, Sandeep

2017-01-01

Dry Eye Disease (DED) is "a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear-film instability with potential damage to the ocular surface." DED comprises two etiologic categories: aqueous-deficient dry eye (ADDE) and evaporative dry eye (EDE). Diagnostic workup of DED should include clinical history, symptom questionnaire, fluorescein TBUT, ocular surface staining grading, Schirmer I/II, lid and meibomian pathology, meibomian expression, followed by other available tests. New diagnostic tests employ the Oculus Keratograph, which performs non-invasive tear-film analysis and a bulbar redness (BR). The TearLab Osmolarity Test enables rapid clinical evaluation of tear osmolarity. Lipiview is a recently developed diagnostic tool that uses interferometry to quantitatively evaluate tear-film thickness. In DED, epithelial and inflammatory cells produce a variety of inflammatory mediators. A stagnant tear film and decreased concentration of mucin result in the accumulation of inflammatory factors that can penetrate tight junctions and cause epithelial cell death. DED treatment algorithms are based on severity of clinical signs and symptoms, and disease etiology. Therapeutic approaches include lubricating artificial tears and immunomodulatory agents.

Early Changes in Ocular Surface and Tear Inflammatory Mediators after Small-Incision Lenticule Extraction and Femtosecond Laser-Assisted Laser In Situ Keratomileusis

PubMed Central

Gao, Shaohui; Li, Saiqun; Liu, Liangping; Wang, Yong; Ding, Hui; Li, Lili; Zhong, Xingwu

2014-01-01

Purpose To characterize the early ocular-surface changes or tear inflammatory-mediators levels following small-incision lenticule extraction (ReLEx smile) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). Methods Forty-seven myopic subjects were recruited for this prospective study. Fifteen underwent ReLEx smile and thirty-two underwent FS-LASIK. Corneal fluorescein (FL) staining, tear break-up time (TBUT), Schirmer I test (SIT), ocular surface disease index (OSDI) and central corneal sensitivity were evaluated in all participants. Tears were collected and analyzed for interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF) and intercellular adhesion molecule-1 (ICAM-1) levels using multiplex magnetic beads. All measurements were preformed preoperatively and 1 day, 1 week, 1 month and 3 months postoperatively. Results FL scores in ReLEx smile group were lower than those of FS-LASIK group 1 week postoperatively (P = 0.010). Compared to the FS-LASIK group, longer TBUT were observed in ReLEx smile group 1 month (P = 0.029) and 3 months (P = 0.045) postoperatively. No significant differences were found in tear secretion for the two groups (P>0.05). OSDI scores were higher in FS-LASIK group 1 month after surgery (P = 0.020). Higher central corneal sensitivity was observed in ReLEx smile group 1 week, 1 month and 3 months (P<0.05) postoperatively. Compared to FS-LASIK group, lower and faster recovery of IL-6 and NGF levels in tears was observed in ReLEx smile group postoperatively (P<0.05). Tears TNF-α and ICAM-1 concentrations were not significantly different between the two groups at any follow-up time (P>0.05). Moreover, IL-6 and NGF levels correlated with ocular surface changes after ReLEx smile or FS-LASIK. Conclusions In the early postoperative period, ReLEx smile results in milder ocular surface changes than FS-LASIK. Furthermore, the tear inflammatory mediators IL-6 and NGF may play a crucial role in the ocular surface healing process following ReLEx smile and FS-LASIK. PMID:25211490

Early changes in ocular surface and tear inflammatory mediators after small-incision lenticule extraction and femtosecond laser-assisted laser in situ keratomileusis.

PubMed

Gao, Shaohui; Li, Saiqun; Liu, Liangping; Wang, Yong; Ding, Hui; Li, Lili; Zhong, Xingwu

2014-01-01

To characterize the early ocular-surface changes or tear inflammatory-mediators levels following small-incision lenticule extraction (ReLEx smile) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). Forty-seven myopic subjects were recruited for this prospective study. Fifteen underwent ReLEx smile and thirty-two underwent FS-LASIK. Corneal fluorescein (FL) staining, tear break-up time (TBUT), Schirmer I test (SIT), ocular surface disease index (OSDI) and central corneal sensitivity were evaluated in all participants. Tears were collected and analyzed for interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF) and intercellular adhesion molecule-1 (ICAM-1) levels using multiplex magnetic beads. All measurements were preformed preoperatively and 1 day, 1 week, 1 month and 3 months postoperatively. FL scores in ReLEx smile group were lower than those of FS-LASIK group 1 week postoperatively (P = 0.010). Compared to the FS-LASIK group, longer TBUT were observed in ReLEx smile group 1 month (P = 0.029) and 3 months (P = 0.045) postoperatively. No significant differences were found in tear secretion for the two groups (P>0.05). OSDI scores were higher in FS-LASIK group 1 month after surgery (P = 0.020). Higher central corneal sensitivity was observed in ReLEx smile group 1 week, 1 month and 3 months (P<0.05) postoperatively. Compared to FS-LASIK group, lower and faster recovery of IL-6 and NGF levels in tears was observed in ReLEx smile group postoperatively (P<0.05). Tears TNF-α and ICAM-1 concentrations were not significantly different between the two groups at any follow-up time (P>0.05). Moreover, IL-6 and NGF levels correlated with ocular surface changes after ReLEx smile or FS-LASIK. In the early postoperative period, ReLEx smile results in milder ocular surface changes than FS-LASIK. Furthermore, the tear inflammatory mediators IL-6 and NGF may play a crucial role in the ocular surface healing process following ReLEx smile and FS-LASIK.

Computer vision syndrome: a review.

PubMed

Blehm, Clayton; Vishnu, Seema; Khattak, Ashbala; Mitra, Shrabanee; Yee, Richard W

2005-01-01

As computers become part of our everyday life, more and more people are experiencing a variety of ocular symptoms related to computer use. These include eyestrain, tired eyes, irritation, redness, blurred vision, and double vision, collectively referred to as computer vision syndrome. This article describes both the characteristics and treatment modalities that are available at this time. Computer vision syndrome symptoms may be the cause of ocular (ocular-surface abnormalities or accommodative spasms) and/or extraocular (ergonomic) etiologies. However, the major contributor to computer vision syndrome symptoms by far appears to be dry eye. The visual effects of various display characteristics such as lighting, glare, display quality, refresh rates, and radiation are also discussed. Treatment requires a multidirectional approach combining ocular therapy with adjustment of the workstation. Proper lighting, anti-glare filters, ergonomic positioning of computer monitor and regular work breaks may help improve visual comfort. Lubricating eye drops and special computer glasses help relieve ocular surface-related symptoms. More work needs to be done to specifically define the processes that cause computer vision syndrome and to develop and improve effective treatments that successfully address these causes.

Ocular surface disease incidence in patients with open-angle glaucoma.

PubMed

Radenković, Marija; Stanković-Babić, Gordana; Jovanović, Predrag; Djordjević-Jocić, Jasmina; Trenkić-Božinović, Marija

2016-01-01

Ocular surface disease (OSD) is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbances, tear film instability with potential damage to the ocular surface, accompanied by increased tear film osmolarity and inflammation of the ocular surface. It is a consequence of disrupted homeostasis of lacrimal functional unit. The main pathogenetic mechanism stems from tear hyperosmolarity and tear film instability. The etiological classification is hyposecretory (Sy-Sjögren and non-Sjögren) and evaporative (extrinsic and intrinsic) form. Delphi panel classification grades disease stages. Antiglaucoma topical therapy causes exacerbation or occurrence of symptoms of dry eye due to main ingredients or preservatives (benzalkonium chloride – BAK), which are dose- and time-dependent. BAK reduces the stability of the lipid layer of tears, the number of goblet cells, induces apoptosis and inflammatory infiltration. The aim of this study was the analysis of the OSD incidence in open-angle glaucoma patients caused by topical medicamentous therapy. Retrospective analysis of examined patients with open-angle glaucoma was used. Increased incidence of moderate and advanced OSD Index degrees in the group of primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma. According to the Delphi Panel Scale the most common grade is IIb (POAG and pseudoexfoliative glaucoma). Evaporative form of OSD prevailed in all treatment groups. High percentage of dry eye in patients with higher concentrations of preservatives applied was noticed. OSD should be timely diagnosed and treated. Dry eye has an impact on surgical outcome and postoperative visual acuity, and in order to improve patient compliance and quality of life, symptoms of dry eye should be addressed and medications with lower concentrations of preservatives should be applied.

Impact of oral vitamin D supplementation on the ocular surface in people with dry eye and/or low serum vitamin D.

PubMed

Yang, Chih-Huang; Albietz, Julie; Harkin, Damien G; Kimlin, Michael G; Schmid, Katrina L

2018-02-01

To determine the possible association between serum vitamin D levels and dry eye symptoms, and the impact of an oral vitamin D supplement. Three linked studies were performed. (i) 29 older adult participants, (ii) 29 dry eyed participants, and (iii) 2-month vitamin D supplementation for 32 dry eyed/low serum vitamin D levelled participants. All participants were assessed by the Ocular Surface Diseases Index (OSDI) to determine dry eye symptoms, and the phenol red thread test (PRT) and/or Schirmer's tear test, tear meniscus height, non-invasive tear break up time, grading ocular surface redness and fluorescein staining of the cornea to detect the tear quality and ocular surface conditions. Blood samples were collected for serum vitamin D analysis and interleukin-6 (IL-6) levels. Among older adult participants, vitamin D levels were negatively correlated with dry eye symptoms, the severity of dry eye, and associated with tired eye symptom. Vitamin D levels of people with dry eye diagnosis were not correlated with OSDI scores and IL-6 levels; while IL-6 levels showed correlation with tear production. In supplement study, vitamin D levels increased by 29mol/l, while dry eye symptoms and grading of corneal staining appeared significant reductions. No significant changes in IL-6 levels. Low vitamin D levels (<50nmol/l) were associated with dry eye symptoms in older individuals but not those diagnosed with dry eye. Vitamin D supplement increased the vitamin D levels, and improved dry eye symptoms, the tear quality and ocular surface conditions. Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

[Oral flaxseed oil (Linum usitatissimum) in the treatment for dry-eye Sjögren's syndrome patients].

PubMed

Pinheiro, Manuel Neuzimar; dos Santos, Procópio Miguel; dos Santos, Regina Cândido Ribeiro; Barros, Jeison de Nadai; Passos, Luiz Fernando; Cardoso Neto, José

2007-01-01

To evaluate if oral flaxseed oil (Linum usitatissimum), which reduces the inflammation in rheumatoid arthritis, may help keratoconjunctivitis sicca's treatment in Sjögren's syndrome patients. In a randomized clinical trial, 38 female patients with rheumatoid arthritis or systemic lupus erithematosus associated with keratoconjunctivitis sicca and Sjögren's syndrome were consecutively selected from patients of the Department of Rheumatology of the Amazonas University Hospital. Keratoconjunctivitis sicca diagnosis was based on a dry-eye symptom survey score (Ocular Surface Disease Index - OSDI), Schirmer-I test, fluorescein break-up time, 1% Rose Bengal staining of ocular surface measured by the van Bijsterveld scale. All patients had ocular surface inflammation evaluated and quantified by conjunctival impression cytology, before and after the study. The subjects were divided into three groups with 13 (Group I), 12 (Group II) and 13 (Group III) patients. Group I received flaxseed oil capsules with a final 1 g/day dosis, Group II flaxseed oil capsules with a final 2 g/day dosis and Group III - controls - placebo, for 180 days. Comparing the results at the beginning and at the end of the treatment, statistically significant changes (p<0.05) in symptoms (OSDI), ocular surface inflammation quantified by conjunctival impression cytology, Schirmer-I test and fluorescein break-up time occurred in Groups I e II when compared to controls. Therapy with oral flaxseed oil capsules 1 or 2 g/day reduces ocular surface inflammation and ameliorates the symptoms of keratoconjunctivitis sicca in Sjögren's syndrome patients. Long-term studies are needed to confirm the role of this therapy for keratoconjunctivitis sicca in Sjögren's syndrome.

Corneal and conjunctival sensory function: the impact on ocular surface sensitivity of change from low to high oxygen transmissibility contact lenses.

PubMed

Golebiowski, Blanka; Papas, Eric B; Stapleton, Fiona

2012-03-09

Deprivation of oxygen to the ocular surface during contact lens wear has been implicated in the alteration of sensory function. This study investigates whether increasing oxygen availability through discontinuation of contact lens wear or transfer into highly oxygen transmissible (high Dk/t) lenses leads to a change in corneal or conjunctival sensitivity. Twenty-seven long-term extended wearers of low Dk/t soft contact lenses ceased lens wear for 1 week and were refitted with high Dk/t silicone hydrogel lenses. A control group of 25 nonwearers matched for age and sex was also recruited. Central corneal and inferior conjunctival sensitivity were measured using an air-jet aesthesiometer. Threshold was determined using a staircase technique. Measurements were taken during low Dk/t lens wear; after 1 week of no wear; and after 1, 3, 6, and 12 months of high Dk/t lens wear. Measurements were carried out on one occasion on the nonwearers. Corneal sensitivity decreased 1 week after discontinuation of low Dk/t lenses and no further change in sensitivity occurred with high Dk/t lens wear. Conjunctival sensitivity did not change over the same time frame. Ocular surface sensitivity in long-term low Dk/t soft lens wearers was similar to that of nonwearers. Sensitivity was higher in females than males in the nonwearers, but not in the lens-wearing group. An interaction of sex on change in conjunctival threshold was found in the lens wearers. These findings indicate that factors other than oxygen availability alone determine sensitivity of the ocular surface. Silicone hydrogel contact lenses appear to have only a minor impact on ocular surface sensitivity in previous lens wearers.

Temperatures of the Ocular Surface, Lid, and Periorbital Regions of Sjögren's, Evaporative, and Aqueous-Deficient Dry Eyes Relative to Normals.

PubMed

Abreau, Kerstin; Callan, Christine; Kottaiyan, Ranjini; Zhang, Aizhong; Yoon, Geunyoung; Aquavella, James V; Zavislan, James; Hindman, Holly B

2016-01-01

To compare the temperatures of the ocular surface, eyelid, and periorbital skin in normal eyes with Sjögren's syndrome (SS) eyes, evaporative dry eyes (EDE), and aqueous deficient dry eyes (ADDE). 10 eyes were analyzed in each age-matched group (normal, SS, EDE, and ADDE). A noninvasive infrared thermal camera captured two-dimensional images in three regions of interest (ROI) in each of three areas: the ocular surface, the upper eyelid, and the periorbital skin within a controlled environmental chamber. Mean temperatures in each ROI were calculated from the videos. Ocular surface time-segmented cooling rates were calculated over a 5-s blink interval. Relative to normal eyes, dry eyes had lower initial central OSTs (SS -0.71°C, EDE -0.55°C, ADDE -0.95°C, KW P<.0001) and lower central upper lid temperatures (SS -0.24°C, ADDE -0.51°C, and EDE -0.54°C, KW P<.0001). ADDE eyes had the lowest initial central OST (P<.0001), while EDE eyes had the lowest central lid temperature and lower periorbital temperatures (P<.0001). Over the 5-s interblink interval, the greatest rate of temperature loss occurred following eyelid opening, but varied by group (normals -0.52, SS -0.73, EDE -0.63, and ADDE -0.75°C/s). The ADDE group also had the most substantial heat loss over the 5-s interblink interval (-0.97°C). Differences in OST may be related to thermal differences in lids and periorbita along with an altered tear film. Thermography of the ocular surface, lids, and surrounding tissues may help to differentiate between different etiologies of dry eye. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic Effect of Human Adipose Tissue-Derived Mesenchymal Stem Cells in Experimental Corneal Failure Due to Limbal Stem Cell Niche Damage.

PubMed

Galindo, Sara; Herreras, José M; López-Paniagua, Marina; Rey, Esther; de la Mata, Ana; Plata-Cordero, María; Calonge, Margarita; Nieto-Miguel, Teresa

2017-10-01

Limbal stem cells are responsible for the continuous renewal of the corneal epithelium. The destruction or dysfunction of these stem cells or their niche induces limbal stem cell deficiency (LSCD) leading to visual loss, chronic pain, and inflammation of the ocular surface. To restore the ocular surface in cases of bilateral LSCD, an extraocular source of stem cells is needed to avoid dependence on allogeneic limbal stem cells that are difficult to obtain, isolate, and culture. The aim of this work was to test the tolerance and the efficacy of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) to regenerate the ocular surface in two experimental models of LSCD that closely resemble different severity grades of the human pathology. hAT-MSCs transplanted to the ocular surface of the partial and total LSCD models developed in rabbits were well tolerated, migrated to inflamed tissues, reduced inflammation, and restrained the evolution of corneal neovascularization and corneal opacity. The expression profile of the corneal epithelial cell markers CK3 and E-cadherin, and the limbal epithelial cell markers CK15 and p63 was lost in the LSCD models, but was partially recovered after hAT-MSC transplantation. For the first time, we demonstrated that hAT-MSCs improve corneal and limbal epithelial phenotypes in animal LSCD models. These results support the potential use of hAT-MSCs as a novel treatment of ocular surface failure due to LSCD. hAT-MSCs represent an available, non-immunogenic source of stem cells that may provide therapeutic benefits in addition to reduce health care expenses. Stem Cells 2017;35:2160-2174. © 2017 AlphaMed Press.

Differential regulation of membrane-associated mucins in the human ocular surface epithelium.

PubMed

Hori, Yuichi; Spurr-Michaud, Sandra; Russo, Cindy Leigh; Argüeso, Pablo; Gipson, Ilene K

2004-01-01

Membrane-associated mucins present in the apical cells of the ocular surface epithelium (MUC1, -4, and -16) are believed to contribute to the maintenance of a hydrated and wet-surfaced epithelial phenotype. Serum and retinoic acid (RA) have been used to treat drying ocular surface diseases. The goal of this study was to determine whether serum or RA regulates the production of membrane-associated mucins in human conjunctival epithelial cells. A telomerase-immortalized human conjunctival epithelial cell line (HCjE) was used. Cells were cultured in serum-free medium to confluence and then cultured with either 10% calf serum or with 100 nM RA for 0 to 72 hours. Conventional RT-PCR was used to determine the expression of retinoic acid receptors (RARs) and quantitative real-time PCR was used to investigate the mRNA expression of MUC1, -4, and -16. Protein levels were assayed by immunoblot analysis, using the antibodies HMFG-2, 1G8, or OC125, which are specific to MUC1, -4 and -16, respectively. To determine whether RA-associated MUC4 mRNA induction is a direct or indirect effect, HCjE cells were treated with RA and the protein synthesis inhibitor cycloheximide (1.0 microg/mL) for 12 hours. MUC1 and -16, but not -4, mRNAs were detectable in HCjE cells grown in serum-free medium. Real-time PCR revealed that MUC4 mRNA was significantly induced by serum 3 hours after its addition, and that MUC1 and MUC16 mRNA levels were significantly upregulated at 72 hours. Western blot analysis demonstrated that the MUC1, -4, and -16 proteins increased over time after addition of serum. Conventional RT-PCR analysis demonstrated that RAR-alpha and -gamma mRNA were expressed in native human conjunctival tissue as well as in the HCjE cells. Treatment with RA upregulated the expression of both MUC4 and -16 mRNA and protein, but MUC1 was unaffected. Because the protein synthesis inhibitor cycloheximide did not prevent the RA-associated induction of MUC4 mRNA, the action of RA on the MUC4 promoter may be direct. The membrane-associated mucins of the ocular surface epithelia, MUC1, -4, and -16, are differentially regulated by serum and RA in the telomerase-immortalized human conjunctival epithelial cell line. Serum derived from vessels in the conjunctiva may play an important role in mucin regulation in the ocular surface epithelia. These data also support the clinical efficacy of autologous serum and RA application in patients with ocular surface diseases. Furthermore, the data suggest that MUC4 and -16 are particularly important hydrophilic molecules involved in maintenance of a healthy ocular surface.

Recent developments on dry eye disease treatment compounds

PubMed Central

Colligris, Basilio; Alkozi, Hanan Awad; Pintor, Jesus

2013-01-01

Dry eye syndrome is a common tears and ocular surface multifactorial disease, described by changes in the ocular surface epithelia related to reduced tears quantity and ocular surface sensitivity, leading to inflammatory reaction. Managing the eye inflammation proved helpful to patients with dry eye disease and current treatment is based on the use of topically applied artificial tear products/lubricants, tear retention management, stimulation of tear secretion and using anti-inflammatory drugs. In this article we revise the corresponding literature and patents assembling the new treatment approaches of novel and future pharmaceutical compounds destined for the dry eye disease treatment. The most frequent categories of compounds presented are secretagogues and anti-inflammatory drugs. These compounds are the research outcome of novel therapeutic strategies designed to reduce key inflammatory pathways and restore healthy tear film. PMID:24526854

Dry eyes: etiology and management.

PubMed

Latkany, Robert

2008-07-01

Until recently, the cause of dry eye syndrome was uncertain and the treatment was palliative. Since discovering that dry eyes are caused by inflammation, there has been an abundance of research focusing on anti-inflammatory therapies, other contributing causes, and better diagnostic testing. This review summarizes some of the interesting published research on ocular surface disease over the past year. The definition of dry eye now highlights the omnipresent symptom of blurry vision. The re-evaluation of ocular surface staining, tear meniscus height, and visual change will allow for a better diagnosis and understanding of dry eyes. Punctal plugs, and oral and topical anti-inflammatory use will strengthen our arsenal against ocular surface disease. Major progress has occurred in the past few years in gaining a better understanding of the etiology of dry eye syndrome, which will inevitably lead to more effective therapeutic options.

Xeroderma pigmentosum at a tertiary care center in Saudi Arabia.

PubMed

Alwatban, Lenah; Binamer, Yousef

2017-01-01

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder caused by defective DNA repair that results in extreme sensitivity to ultraviolet (UV) rays. Depending on the type of XP, the disease may affect the skin, eyes and nervous system. Describe the dermatologic manifestations in patients suffering from XP. Retrospective, descriptive review of medical records. Dermatology clinic at tertiary care center in Riyadh. This study included Saudi patients with clinically confirmed XP. Demographic and clinical data including pathology and associated conditions and outcomes. Of 21 patients with XP, the most common manifestation was lentigines, affecting 18 patients (86%). The most common skin cancer was basal cell carcinoma followed by squamous cell carcinoma (SCC) affecting 15 (71.4%) and 9 (42.8%), respectively. Other skin findings included neurofibroma, trichilemmoma and seborrheic keratosis. Ocular involvement included photophobia, which was the most common finding followed by dryness and ocular malignancies. Two patients showed neurological involvement, which correlated with the type of mutation. Considering that XP is a rare genetic disease, this description of our patient population will aid in early recognition and diagnosis. Retrospective and small number of patients. Genetic analyses were done for only 5 of the 21 patients.

Indications for eye removal over a 13-year period at an ophthalmology referral center in São Paulo, Brazil.

PubMed

Hime, Bernardo; Isenberg, Jordan; Rocha, Gustavo; Lowen, Marcia; Morales, Melina; Fernandes, Bruno Franco; Belfort, Rubens N

2017-01-01

To analyze the indications and types of eye removal at Latin America's highest-volume ophthalmic reference center in São Paulo, Brazil. A retrospective analysis was conducted of surgical pathological reports in the electronic database of the Ophthalmology Department of the Universidade Federal de São Paulo Hospital of patients who underwent eye-removal procedures between January 2000 and December 2012. A total of 412 cases met the inclusion criteria for this study. The most common indications for eye removal were ocular melanoma and retinoblastoma, representing 35.4% and 31.1% of the total cases, respectively. Other frequent indications included endophthalmitis (6.3%), nonspecific inflammation (4.1%), squamous cell carcinoma (3.6%), panophthalmitis (3.4%), and phthisis bulbi (1.2%). The remaining indications accounted for 14.8% of all cases, with each accounting for <1% of the total cases. Enucleation was the most common eye-removal procedure seen in our study. The two most common indications for eye removal were ocular melanoma and retinoblastoma. Alternative treatment options are effective in limiting the need for eye removal but are constrained by our public center's so cioeconomic context.

Dry eye disease caused by viral infection: review.

PubMed

Alves, Monica; Angerami, Rodrigo Nogueira; Rocha, Eduardo Melani

2013-01-01

Dry eye disease and ocular surface disorders may be caused or worsened by viral agents. There are several known and suspected virus associated to ocular surface diseases. The possible pathogenic mechanisms for virus-related dry eye disease are presented herein. This review serves to reinforce the importance of ophthalmologists as one of the healthcare professional able to diagnose a potentially large number of infected patients with high prevalent viral agents.

Relevance of Lipid-Based Products in the Management of Dry Eye Disease

PubMed Central

Amrane, Mourad; Faure, Marie-Odile; Holopainen, Juha M.; Tong, Louis

2017-01-01

Abstract Components of the ocular surface synergistically contribute to maintaining and protecting a smooth refractive layer to facilitate the optimal transmission of light. At the air–water interface, the tear film lipid layer (TFLL), a mixture of lipids and proteins, plays a key role in tear surface tension and is important for the physiological hydration of the ocular surface and for ocular homeostasis. Alterations in tear fluid rheology, differences in lipid composition, or downregulation of specific tear proteins are found in most types of ocular surface disease, including dry eye disease (DED). Artificial tears have long been a first line of treatment in DED and aim to replace or supplement tears. More recently, lipid-containing eye drops have been developed to more closely mimic the combination of aqueous and lipid layers of the TFLL. Over the last 2 decades, our understanding of the nature and importance of lipids in the tear film in health and disease has increased substantially. The aim of this article is to provide a brief overview of our current understanding of tear film properties and review the effectiveness of lipid-based products in the treatment of DED. Liposome lid sprays, emulsion eye drops, and other lipid-containing formulations are discussed. PMID:28956698

Comparison of Cornea Module and DermaInspect for noninvasive imaging of ocular surface pathologies

NASA Astrophysics Data System (ADS)

Steven, Philipp; Müller, Maya; Koop, Norbert; Rose, Christian; Hüttmann, Gereon

2009-11-01

Minimally invasive imaging of ocular surface pathologies aims at securing clinical diagnosis without actual tissue probing. For this matter, confocal microscopy (Cornea Module) is in daily use in ophthalmic practice. Multiphoton microscopy is a new optical technique that enables high-resolution imaging and functional analysis of living tissues based on tissue autofluorescence. This study was set up to compare the potential of a multiphoton microscope (DermaInspect) to the Cornea Module. Ocular surface pathologies such as pterygia, papillomae, and nevi were investigated in vivo using the Cornea Module and imaged immediately after excision by DermaInspect. Two excitation wavelengths, fluorescence lifetime imaging and second-harmonic generation (SHG), were used to discriminate different tissue structures. Images were compared with the histopathological assessment of the samples. At wavelengths of 730 nm, multiphoton microscopy exclusively revealed cellular structures. Collagen fibrils were specifically demonstrated by second-harmonic generation. Measurements of fluorescent lifetimes enabled the highly specific detection of goblet cells, erythrocytes, and nevus-cell clusters. At the settings used, DermaInspect reaches higher resolutions than the Cornea Module and obtains additional structural information. The parallel detection of multiphoton excited autofluorescence and confocal imaging could expand the possibilities of minimally invasive investigation of the ocular surface toward functional analysis at higher resolutions.

Investigational and experimental drugs for intraocular pressure reduction in ocular hypertension and glaucoma.

PubMed

Lusthaus, Jed Asher; Goldberg, Ivan

2016-10-01

Intraocular pressure (IOP) is the most significant modifiable risk factor to prevent onset or progression of glaucoma. Glaucoma prevalence continues to increase, emphasizing the need for improved ocular hypotensive treatment options. To try to improve on both tolerance and IOP control of currently available therapies, different receptors or mechanisms are being explored to reduce IOP more effectively and to improve tolerance. We review synthetic topical and oral drugs in early development for the management of ocular hypertension and glaucoma. New therapeutic agents for IOP control have been discovered; some appear to be reasonably tolerated. IOP reduction may be limited with some agents, but other benefits although unproven may compensate for this, such as less ocular surface disease, enhanced neuro-protection or increased ocular blood flow. Further product development promises improved treatment options for ocular hypertensives and glaucoma sufferers.

Ocular surface disease in patients with glaucoma or ocular hypertension treated with either BAK-preserved latanoprost or BAK-free travoprost

PubMed Central

Katz, Gregory; Springs, Clark L; Craven, E Randy; Montecchi-Palmer, Michela

2010-01-01

Purpose The preservative benzalkonium chloride (BAK) may adversely affect ocular surface health. This study evaluated symptoms of ocular surface disease (OSD) in patients previously treated with a BAK-preserved therapy to lower their intraocular pressure, who either continued that therapy or switched to a BAK-free therapy. Methods Eligible adult patients with ocular hypertension or open-angle glaucoma that had been controlled with BAK-preserved latanoprost 0.005% monotherapy (Xalatan®) for at least one month and had a score of ≥ 13 (0 = none, 100 = most severe) on the Ocular Surface Disease Index (OSDI) questionnaire were entered into this prospective, double-masked, randomized, active-controlled, multicenter trial. By random assignment, patients either continued with BAK-preserved latanoprost 0.005% or transitioned to BAK-free travoprost 0.004% (Travatan Z® ophthalmic solution). OSDI scores were assessed again after six and 12 weeks. Results For the 678 evaluable patients, mean change in OSDI score from baseline to week 12 favored the travoprost 0.004% BAK-free group, but was not statistically different between groups (P = 0.10). When patients with mild OSD at baseline were assessed after 12 weeks, the mean OSDI score was significantly lower (P = 0.04) in the BAK-free travoprost 0.004% group (score = 11.6 ± 10.8 units) than in the BAK-preserved latanoprost 0.005% group (score = 14.4 ± 11.9 units), and a significantly larger percentage (P < 0.01) improved to normal OSDI scores in the BAK-free travoprost 0.004% group (62.9% of group) than in the BAK-preserved latanoprost 0.005% group (47.0% of group). Patients pretreated with BAK-preserved latanoprost 0.005% for >24 months were significantly more likely (P = 0.03) to improve to a normal OSDI score after 12 weeks if they were switched to BAK-free travoprost 0.004% (47.9% of group) than if they remained on BAK-preserved latanoprost 0.005% (33.9% of group). Conclusions Switching from BAK-preserved latanoprost 0.005% to BAK-free travoprost 0.004% yielded significant improvements in symptoms of OSD in patients with glaucoma or ocular hypertension. PMID:21151330

Randomised masked trial of the clinical safety and tolerability of MGO Manuka Honey eye cream for the management of blepharitis

PubMed Central

Craig, Jennifer P; Wang, Michael T M; Ganesalingam, Kalaivarny; Rupenthal, Ilva D; Swift, Simon; Loh, Chee Seang; Te Weehi, Leah; Cheung, Isabella M Y; Watters, Grant A

2017-01-01

Objective To assess the clinical safety and tolerability of a novel MGO Manuka Honey microemulsion (MHME) eye cream for the management of blepharitis in human subjects. Methods and analysis Twenty-five healthy subjects were enrolled in a prospective, randomised, paired-eye, investigator-masked trial. The MHME eye cream (Manuka Health New Zealand) was applied to the closed eyelids of one eye (randomised) overnight for 2 weeks. LogMAR visual acuity, eyelid irritation symptoms, ocular surface characteristics and tear film parameters were assessed at baseline, day 7 and day 14. Expression of markers of ocular surface inflammation (matrix metalloproteinase-9 and interleukin-6) and goblet cell function (MUC5AC) were quantified using impression cytology at baseline and day 14. Results There were no significant changes in visual acuity, eyelid irritation symptoms, ocular surface characteristics, tear film parameters and inflammatory marker expression during the 2-week treatment period in treated and control eyes (all p>0.05), and measurements did not differ significantly between eyes (all p>0.05). No major adverse events were reported. Two subjects experienced transient ocular stinging, presumably due to migration of the product into the eye, which resolved following aqueous irrigation. Conclusion The MHME eye cream application was found to be well tolerated in healthy human subjects and was not associated with changes in visual acuity, ocular surface characteristics, tear film parameters, expression of markers of inflammation or goblet cell function. The findings support future clinical efficacy trials in patients with blepharitis. Trial registration number ACTRN12616000540415 PMID:29354710

Analysis of Factors Associated With the Tear Film Lipid Layer Thickness in Normal Eyes and Patients With Dry Eye Syndrome.

PubMed

Jung, Ji Won; Park, Si Yoon; Kim, Jin Sun; Kim, Eung Kweon; Seo, Kyoung Yul; Kim, Tae-Im

2016-08-01

To determine the effects of clinical variables, including age, sex, history of refractive or cataract surgery, contact lens use, and ocular surface and meibomian gland parameters on the lipid layer thickness (LLT) in normal subjects and patients with dry eye syndrome (DES). A total of 64 normal subjects and 326 patients with DES were enrolled, and they underwent measurements of LLT with a LipiView interferometer and tear meniscus height using optical coherence tomography, tear film break-up time (TBUT) determination, ocular surface staining, Schirmer's test, examination of the lid margins and meibomian glands, and assessment using the Ocular Surface Disease Index (OSDI). In normal subjects, the median (range) LLT was 67 (33-100) nm, and age was the only factor that was significantly associated with LLT (β = 0.678, P = 0.028). In patients with DES, the median (range) LLT was 84 (20-100) nm, and 79.0% of the participants fulfilled the diagnostic criteria for meibomian gland dysfunction (MGD). In a multivariate analysis, increased age and female sex were significantly related to increased LLT (β = 0.282, P = 0.005 and β = 11.493, P < 0.001), and hypersecretory MGD and lid margin inflammation were independently associated with increased LLT (β = 11.299, P = 0.001 and β = 12.747, P = 0.001). Lipid layer thickness measurements using a new interferometer are significantly affected by demographic factors such as age, sex, ocular surgical history, and MGD type. Therefore, all of these factors must be considered in the diagnosis of ocular surface diseases.

Ocular surface temperature in patients with evaporative and aqueous-deficient dry eyes: a thermographic approach.

PubMed

Matteoli, S; Favuzza, E; Mazzantini, L; Aragona, P; Cappelli, S; Corvi, A; Mencucci, R

2017-07-26

In recent decades infrared thermography (IRT) has facilitated accurate quantitative measurements of the ocular surface temperature (OST), applying a non-invasive procedure. The objective of this work was to develop a procedure based on IRT, which allows characterizing of the cooling of the ocular surface of patients suffering from dry eye syndrome, and distinguishing among patients suffering from aqueous deficient dry eye (ADDE) and evaporative dry eyes (EDE). All patients examined (34 females and 4 males, 23-84 years) were divided into two groups according to their Schirmer I result (⩽ 7 mm for ADDE and  >  7 mm for EDE), and the OST was recorded for 7 s at 30 Hz. For each acquisition, the temperatures of the central cornea (CC) as well as those of both temporal and nasal canthi were investigated. Findings showed that the maximum temperature variation (up to 0.75  ±  0.29 °C) was at the CC for both groups. Furthermore, patients suffering from EDE tended to have a higher initial OST than those with ADDE, explained by the greater quantity of the tear film, evenly distributed over the entire ocular surface, keeping the OST higher initially. Results also showed that EDE patients had an average cooling rate higher than those suffering from ADDE, confirming the excessive evaporation of the tear film. Ocular thermography paves the way to become an effective tool for differentiating between the two different etiologies of dry eye syndrome.

Ocular complications of diabetes mellitus

PubMed Central

Sayin, Nihat; Kara, Necip; Pekel, Gökhan

2015-01-01

Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world’s most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases. PMID:25685281

Evaluation of Ocular Surface Disease in Patients with Glaucoma

PubMed Central

Mathews, Priya M.; Ramulu, Pradeep Y.; Friedman, David S.; Utine, Canan A.; Akpek, Esen K.

2013-01-01

Purpose To evaluate the subjective and objective measures of ocular surface disease in patients with glaucoma. Design Cross-sectional study. Participants Sixty-four glaucoma subjects with bilateral visual field (VF) loss and 59 glaucoma suspects with normal VFs. Methods Consecutive patients were recruited prospectively from the Wilmer Eye Institute Glaucoma Clinic. Main Outcome Measures Tear film breakup time (TBUT), corneal staining score (0–15), and Schirmer’s test results were included as objective metrics, whereas the Ocular Surface Disease Index (OSDI) questionnaire was administered to assess symptoms. Total OSDI score, vision-related subscore (derived from questions about vision and task performance), and discomfort-related subscore (derived from questions about ocular surface discomfort) were calculated for each subject. Results Seventy-five percent (48/64) of glaucoma subjects and 41% (24/59) of glaucoma suspects were receiving topical medications. The corneal staining grade was greater in glaucoma subjects than in glaucoma suspects (6.4 vs. 4.1; P<0.001), but groups did not differ with regard to TBUT or Schirmer’s results (P>0.20 for both). Multivariate regression models showed that topical glaucoma therapy burden was associated with a significantly higher total corneal staining grade (β, +0.9 for each additional glaucoma drop; 95% confidence interval [CI], 0.5–1.3; P<0.001), but not with TBUT or Schirmer’s results (P>0.20 for both). Glaucoma subjects had significantly higher total OSDI scores than glaucoma suspects (16.7 vs. 7.9; P<0.001). This largely was the result of higher vision-related subscores in the glaucoma group (11.1 vs. 3.3; P<0.001). Ocular discomfort–related subscores, however, were similar in both groups (5.7 vs. 4.6; P = 0.30). In multivariate analyses, each 5-decibel decrement in better-eye VF mean deviation was associated with a 4.7-point increase in total OSDI score (95% CI, 1.9–7.5; P = 0.001) and a 3.7-point increase in the vision-related subscore (95% CI, 1.7–5.6; P<0.001) but did not predict a higher discomfort-related subscore (β, 1.1 point; P = 0.07). Topical glaucoma therapy burden was not associated with higher total OSDI score or vision- or discomfort-related subscore (P>0.20 for all). Conclusions Glaucoma is associated with significant ocular surface disease, and topical glaucoma therapy burden seems predictive of corneal staining severity. However, OSDI is a poor metric for capturing ocular surface disease in glaucoma because symptoms seem to be related largely to VF loss. PMID:23714318

Microbial Keratitis: Could Contact Lens Material Affect Disease Pathogenesis?

PubMed Central

Evans, David J.; Fleiszig, Suzanne M. J.

2012-01-01

Microbial keratitis is a sight-threatening complication associated with contact lenses. The introduction of silicone hydrogel lens materials with increased oxygen transmission to the ocular surface has not significantly altered the incidence of microbial keratitis. These data suggest that alternate, or additional, predisposing factors involving lens wear must be addressed to reduce or eliminate these infections. The contact lens can provide a surface for microbial growth in situ, and can also influence ocular surface homeostasis through effects on the tear fluid and corneal epithelium. Thus, it is intuitive that future contact lens materials could make a significant contribution to preventing microbial keratitis. Design of the “right” material to prevent microbial keratitis requires understanding the effects of current materials on bacterial virulence in the cornea, and on ocular surface innate defenses. Current knowledge in each of these areas will be presented, with a discussion of future directions needed to understand the influence of lens material on the pathogenesis of microbial keratitis. PMID:23266587

Lacritin and Other New Proteins of the Lacrimal Functional Unit

PubMed Central

McKown, Robert L.; Wang, Ningning; Raab, Ronald W.; Karnati, Roy; Zhang, Yinghui; Williams, Patricia B.; Laurie, Gordon W.

2009-01-01

The lacrimal functional unit (LFU) is defined by the 2007 International Dry Eye WorkShop as ‘an integrated system comprising the lacrimal glands, ocular surface (cornea, conjunctiva and meibomian glands) and lids, and the sensory and motor nerves that connect them’. The LFU maintains a healthy ocular surface primarily through a properly functioning tear film that provides protection, lubrication, and an environment for corneal epithelial cell renewal. LFU cells express thousands of proteins. Over two hundred new LFU proteins have been discovered in the last decade. Lacritin is a new LFU-specific growth factor in human tears that flows through ducts to target corneal epithelial cells on the ocular surface. When applied topically in rabbits, lacritin appears to increase the volume of basal tear secretion. Lacritin is one of only a handful of tear proteins preliminarily reported to be downregulated in blepharitis and in two dry eye syndromes. Computational analysis predicts an ordered C-terminal domain that binds the corneal epithelial cell surface proteoglycan syndecan-1 (SDC1) and is required for lacritin’s low nanomolar mitogenic activity. The lacritin binding site on the N-terminus of SDC1 is exposed by heparanase. Heparanase is constitutively expressed by the corneal epithelium and appears to be a normal constituent of tears. Binding triggers rapid signaling to downstream NFAT and mTOR. A wealth of other new proteins, originally designated as hypothetical when first identified by genomic sequencing, are expressed by the human LFU including: ALS2CL, ARHGEF19, KIAA1109, PLXNA1, POLG, WIPI1 and ZMIZ2. Their demonstrated or implied roles in human genetic disease or basic cellular functions are fuel for new investigation. Addressing topical areas in ocular surface physiology with new LFU proteins may reveal interesting new biological mechanisms and help get to the heart of ocular surface dysfunction. PMID:18840430

Efficacy of a New Ocular Surface Modulator in Restoring Epithelial Changes in an In Vitro Model of Dry Eye Syndrome.

PubMed

Barabino, Stefano; De Servi, Barbara; Aragona, Salvatore; Manenti, Demetrio; Meloni, Marisa

2017-03-01

So far tear substitutes have demonstrated a limited role in restoring ocular surface damage in dry eye syndrome (DES). The aim of this study was to assess the efficacy of a new ocular surface modulator in an in vitro model of human corneal epithelium (HCE) damaged by severe osmotic stress mirroring the features of dry eye conditions. A reconstructed HCE model challenged by the introduction of sorbitol in the culture medium for 16 h was used to induce an inflammatory pathway and to impair the tight junctions integrity determining a severe modification of the superficial layer ultrastructure. At the end of the overnight stress period in the treated HCE series, 30 μl of the ocular surface modulator (T-LysYal, Sildeha, Switzerland) and of hyaluronic acid (HA) in the control HCE series were applied for 24 h. The following parameters were quantified: scanning electron microscopy (SEM), trans-epithelial electrical resistance (TEER), immunofluorescence analysis of integrin β1 (ITG-β1), mRNA expression of Cyclin D-1 (CCND1), and ITG-β1. In the positive control after the osmotic stress the HCE surface damage was visible at the ultrastructural level with loss of cell-cell interconnections, intercellular matrix destruction, and TEER reduction. After 24 h of treatment with T-LysYal, HCE showed a significant improvement of the ultrastructural morphological organization and increased expression of ITG-β1 at the tissue level when compared to positive and control series. A significant increase of mRNA expression for ITG-β1 and CCND1 was shown in the HA-treated cells compared to T-LysYal. TEER measurement showed a significant reduction in all groups after 16 h without modifications after the treatment period. This study has shown the possibility of a new class of agents denominated ocular surface modulators to restore corneal cells damaged by dry eye conditions. Further in vivo studies are certainly necessary to confirm these results.

Comparison of efficacy and ocular surface toxicity of topical preservative-free methylprednisolone and preserved prednisolone in the treatment of acute anterior uveitis.

PubMed

Hedayatfar, Alireza; Hashemi, Hassan; Asgari, Soheila; Chee, Soon-Phaik

2014-04-01

The aim of this study was to compare the antiinflammatory effect and ocular surface toxicity of topical nonpreserved methylprednisolone sodium succinate 1% and preserved prednisolone acetate suspension 1% for the management of acute anterior uveitis (AAU). In this prospective, randomized, investigator-masked, comparative clinical trial, patients with mild-to-moderate noninfectious AAU were assigned randomly to receive either hourly nonpreserved methylprednisolone 1% (group A) or preserved prednisolone 1% (group B) eye drops followed by a 2-week tapering regimen. Anterior chamber cells and flare were clinically evaluated for the objective comparison of the antiinflammatory effect. The main outcome measure was the percentage of patients with a resolution of inflammation (anterior chamber cells <1+) on day 14. Ocular surface toxicity was assessed by means of the corneal fluorescein staining score, tear breakup time, Schirmer I test, and questionnaire-based grading of ocular discomfort parameters. Seventy-two eyes of 68 patients were studied, of which 38 eyes were enrolled in group A and 34 eyes were enrolled in group B. On day 14, 76.3% of the patients in group A had resolution of inflammation compared with 70.6% of the patients in group B, proving noninferiority (χ = 0.303, P = 0.582). The mean anterior chamber cell grade reduction for patients in group A was similar to that in group B (2.52 vs. 2.86, respectively; P = 0.92). Group A patients showed significantly lower corneal fluorescein staining scores (P < 0.001) and reported milder subjective ocular discomfort (0.55 vs. 1.43, P = 0.01) as compared with group B. Both preparations demonstrated equal antiinflammatory effects for the treatment of AAU. Nonpreserved methylprednisolone eye drops exhibited a significantly lower ocular surface toxicity profile and milder subjective discomfort when compared with that exhibited by preserved prednisolone.

The zebrafish eye—a paradigm for investigating human ocular genetics

PubMed Central

Richardson, R; Tracey-White, D; Webster, A; Moosajee, M

2017-01-01

Although human epidemiological and genetic studies are essential to elucidate the aetiology of normal and aberrant ocular development, animal models have provided us with an understanding of the pathogenesis of multiple developmental ocular malformations. Zebrafish eye development displays in depth molecular complexity and stringent spatiotemporal regulation that incorporates developmental contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar to that seen in humans. For this reason, and due to its genetic tractability, external fertilisation, and early optical clarity, the zebrafish has become an invaluable vertebrate system to investigate human ocular development and disease. Recently, zebrafish have been at the leading edge of preclinical therapy development, with their amenability to genetic manipulation facilitating the generation of robust ocular disease models required for large-scale genetic and drug screening programmes. This review presents an overview of human and zebrafish ocular development, genetic methodologies employed for zebrafish mutagenesis, relevant models of ocular disease, and finally therapeutic approaches, which may have translational leads in the future. PMID:27612182

Development of infrared thermal imager for dry eye diagnosis

NASA Astrophysics Data System (ADS)

Chiang, Huihua Kenny; Chen, Chih Yen; Cheng, Hung You; Chen, Ko-Hua; Chang, David O.

2006-08-01

This study aims at the development of non-contact dry eye diagnosis based on an infrared thermal imager system, which was used to measure the cooling of the ocular surface temperature of normal and dry eye patients. A total of 108 subjects were measured, including 26 normal and 82 dry eye patients. We have observed that the dry eye patients have a fast cooling of the ocular surface temperature than the normal control group. We have developed a simplified algorithm for calculating the temperature decay constant of the ocular surface for discriminating between normal and dry eye. This study shows the diagnostic of dry eye syndrome by the infrared thermal imager system has reached a sensitivity of 79.3%, a specificity of 75%, and the area under the ROC curve 0.841. The infrared thermal imager system has a great potential to be developed for dry eye screening with the advantages of non-contact, fast, and convenient implementation.

Molecular Histopathology Using Gold Nanorods and Optical Coherence Tomography

PubMed Central

Prabhulkar, Shradha; Matthews, Jared; Rawal, Siddarth; Awdeh, Richard M.

2013-01-01

Purpose. To examine the novel application of a commercially available optical coherence tomography (OCT) system toward molecular histopathology using gold nanorod (GNR) linked antibodies as a functionalized contrast agent to evaluate ocular surface squamous neoplasia (OSSN). Methods. GNRs were synthesized and covalently attached to anti–glucose transporter-1 (GLUT-1) antibodies via carbodiimide chemistry. Three specimens from each of three distinct categories of human conjunctival tissue were selected for analysis, including conjunctiva without epithelial atypia (controls); conjunctival intraepithelial neoplasia, carcinoma in situ (CIS); and conjunctival squamous cell carcinoma (SCC). Tissue sections were incubated initially with GNR tagged anti–GLUT-1 antibodies and then with a fluorescent-tagged secondary antibody. Immunofluorescence and OCT imaging of the tissue was performed and the results were correlated to the light microscopic findings on traditional hemotoxyin and eosin stained sections. Results. No binding of the functionalized GNRs was observed within the epithelium of three normal conjunctiva controls. While immunofluorescence disclosed variable binding of the functionalized GNRs to atypical epithelial cells in all six cases of OSSN, the enhancement of the OCT signal in three cases of CIS was insufficient to distinguish these specimens from normal controls. In two of three cases of SCC, binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to atypical epithelial cells which stained intensely on immunofluorescence imaging. Binding of functionalized GNRs was sufficient to produce an increased scattering effect on OCT in areas correlating to regions of erythrocytes and hemorrhage which stained intensely on immunofluorescence imaging within all nine tested samples. Conclusions. We have demonstrated the use of OCT for molecular histopathology using functionalized gold nanorods in the setting of OSSN. Our results suggest a threshold concentration of functionalized GNRs within tissue is required to achieve a detectable enhancement in scattering of the OCT signal. PMID:23307958

Primary iris stromal cyst with rapid growth.

PubMed

Xiao, Yang; Wang, Yu-Hong; Niu, Gai-Ling; Gao, Min

2009-11-01

To describe the clinical features and the surgical management of primary iris stromal cyst with rapid growth. A 14-year-old Chinese-Mongolian girl was referred to us with a 1-month history of obstructed vision and photophobia. On an examination, a semitransparent cyst with a densely pigmented posterior wall was revealed in the anterior chamber of the left eye. The information regarding the location and extent of the cyst was further analyzed by anterior segment optical coherence tomography and ultrasound biomicroscopy. It arose within the iris stroma, measuring 7.52 x 3.60 mm. Blood vessels on the surface of the lesion were revealed by iris angiography. There was no history of amniocentesis, birth trauma, antecedent ocular injury, or maternal illness during gestation. The diagnosis of primary iris stromal cyst was made. A combination of needle aspiration, piecemeal resection of cyst wall, cryotherapy, and argon laser photocoagulation with overlapped spots was used. Histopathology of the cyst wall revealed nonkeratinized, multilayered, stratified squamous epithelium with clusters of goblet cells. Complete resolution of the cyst was successfully achieved. The visual acuity improved to 20/25 from counting fingers. At 6 months of follow-up, there was no recurrence. Complete eradication and devitalization of any remaining epithelial cells are the key factors for preventing recurrence and diffuse epithelialization of the anterior chamber.

Chronic dry eye in PRK and LASIK: manifestations, incidence and predictive factors

PubMed Central

Bower, Kraig S.; Sia, Rose K.; Ryan, Denise S.; Mines, Michael J.; Dartt, Darlene A.

2017-01-01

Purpose To evaluate dry eye manifestations following photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) and determine the incidence and predictive factors of chronic dry eye using a set of dry eye criteria. Setting Walter Reed Army Medical Center, Washington, DC, USA Methods This is a prospective non-randomized clinical study of 143 active duty U.S. Army personnel aged 29.9±5.2 years with myopia or myopic astigmatism (manifest spherical equivalent −3.83±1.96 diopters) undergoing either PRK or LASIK. Dry eye evaluation was performed pre- and postoperatively. Main outcome measures included dry eye manifestations, incidence, and predictive factors of chronic dry eye. Results Schirmer scores, corneal sensitivity, ocular surface staining, surface regularity index (SRI), and responses to dry eye questionnaire significantly changed over time after PRK. After LASIK, significant changes were observed in tear breakup time, corneal sensitivity, ocular surface staining, and responses to questionnaire. At twelve months postoperatively, 5.0% of PRK and 0.8% of LASIK participants developed chronic dry eye. Regression analysis showed preoperatively lower Schirmer score will significantly influence development of chronic dry eye after PRK whereas preoperatively lower Schirmer score or higher ocular surface staining score will significantly influence the occurrence of chronic dry eye after LASIK. Conclusions Chronic dry eye is uncommon after PRK and LASIK. Ocular surface and tear film characteristics during preoperative examination may help predict chronic dry eye development in PRK and LASIK. PMID:26796443

Clinical implications of mast cell involvement in allergic conjunctivitis.

PubMed

Elieh Ali Komi, D; Rambasek, T; Bielory, L

2018-03-01

The conjunctiva is a common site for the allergic inflammatory response due to it being highly vascularized, having constant exposure to environmental pollutants and allergenic pollens and having a unique conjunctival associated lymphoid tissue. The primary morbidity of anterior surface conjunctival disorders that include allergic conjunctivitis and tear film disorders is associated with its high frequency of involvement rather than its severity, although the more chronic forms can involve the cornea and lead to sight-threatening conditions. Ocular allergy is associated with IgE-mediated mast cell activation in conjunctival tissue leading to the release of preformed mediators including histamine and proteases and subsequent de novo formation of lipid-derived mediators and cytokines that trigger a cascade of cellular and molecular events leading to extensive migration and infiltration of inflammatory cells to the ocular surface. The trafficking of neutrophils, eosinophils, and lymphocytes to the ocular surface is due to establishing various chemokine gradients (mainly CCL11, CCL24, CCL5, MCP-3, and MCP-4), cell surface expression of adhesion molecules (such as VCAM-1 the ligand for VLA-4), and leukocyte adhesion to vascular endothelium. The release of preformed mediators underlies the acute ocular surface response while the secondary influx of inflammatory cells leading to the recruitment and activation of eosinophils and the subsequent activation of Th2 and Th1 lymphocytes at the level of the conjunctiva reflects the late-phase reaction. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Alkali Burn of the Ocular Surface Associated With a Commonly Used Antifog Agent for Eyewear: Two Cases and a Review of Previous Reports.

PubMed

Welling, John D; Pike, Evan C; Mauger, Thomas F

2016-02-01

To report 2 cases of ocular chemical burns associated with the use of a swim goggle antifog agent and to review the literature for this and similar antifog products. Case reports and systematic review of the medical literature, material safety data, product safety reports, and consumer reviews. Two males, one 46 years and the other 41 years, were referred to our clinic with chemical burns of the ocular surface after using the same goggle antifog agent while swimming in a triathlon. Both sustained significant epithelial defects. Fortunately, with prompt treatment, both of our patients returned to their baseline vision within a few weeks without suffering sight-threatening complications. These are the first cases of ocular chemical burn secondary to use of an eyewear antifog agent to be reported in the medical literature. Similar reports found in consumer forums suggest that our cases are not isolated and these products may have the potential to cause vision-threatening chemical burns.

Ocular chemical injuries and their management.

PubMed

Singh, Parul; Tyagi, Manoj; Kumar, Yogesh; Gupta, K K; Sharma, P D

2013-05-01

Chemical burns represent potentially blinding ocular injuries and constitute a true ocular emergency requiring immediate assessment and initiation of treatment. The majority of victims are young and exposure occurs at home, work place and in association with criminal assaults. Alkali injuries occur more frequently than acid injuries. Chemical injuries of the eye produce extensive damage to the ocular surface epithelium, cornea, anterior segment and limbal stem cells resulting in permanent unilateral or bilateral visual impairment. Emergency management if appropriate may be single most important factor in determining visual outcome. This article reviews the emergency management and newer techniques to improve the prognosis of patients with chemical injuries.

In Vivo Confocal Microscopy of the Ocular Surface: From Bench to Bedside

PubMed Central

Villani, Edoardo; Baudouin, Christophe; Efron, Nathan; Hamrah, Pedram; Kojima, Takashi; Patel, Sanjay V.; Pflugfelder, Stephen C.; Zhivov, Andrey; Dogru, Murat

2014-01-01

In vivo confocal microscopy (IVCM) is an emerging technology that provides minimally invasive, high resolution, steady-state assessment of the ocular surface at the cellular level. Several challenges still remain but, at present, IVCM may be considered a promising technique for clinical diagnosis and management. This mini-review summarizes some key findings in IVCM of the ocular surface, focusing on recent and promising attempts to move “from bench to bedside”. IVCM allows prompt diagnosis, disease course follow-up, and management of potentially blinding atypical forms of infectious processes, such as acanthamoeba and fungal keratitis. This technology has improved our knowledge of corneal alterations and some of the processes that affect the visual outcome after lamellar keratoplasty and excimer keratorefractive surgery. In dry eye disease, IVCM has provided new information on the whole-ocular surface morphofunctional unit. It has also improved understanding of pathophysiologic mechanisms and helped in the assessment of prognosis and treatment. IVCM is particularly useful in the study of corneal nerves, enabling description of the morphology, density, and disease- or surgically induced alterations of nerves, particularly the subbasal nerve plexus. In glaucoma, IVCM constitutes an important aid to evaluate filtering blebs, to better understand the conjunctival wound healing process, and to assess corneal changes induced by topical antiglaucoma medications and their preservatives. IVCM has significantly enhanced our understanding of the ocular response to contact lens wear. It has provided new perspectives at a cellular level on a wide range of contact lens complications, revealing findings that were not previously possible to image in the living human eye. The final section of this mini-review provides a focus on advances in confocal microscopy imaging. These include 2D wide-field mapping, 3D reconstruction of the cornea and automated image analysis. PMID:24215436

Co-ordinated ocular development from human iPS cells and recovery of corneal function.

PubMed

Hayashi, Ryuhei; Ishikawa, Yuki; Sasamoto, Yuzuru; Katori, Ryosuke; Nomura, Naoki; Ichikawa, Tatsuya; Araki, Saori; Soma, Takeshi; Kawasaki, Satoshi; Sekiguchi, Kiyotoshi; Quantock, Andrew J; Tsujikawa, Motokazu; Nishida, Kohji

2016-03-17

The eye is a complex organ with highly specialized constituent tissues derived from different primordial cell lineages. The retina, for example, develops from neuroectoderm via the optic vesicle, the corneal epithelium is descended from surface ectoderm, while the iris and collagen-rich stroma of the cornea have a neural crest origin. Recent work with pluripotent stem cells in culture has revealed a previously under-appreciated level of intrinsic cellular self-organization, with a focus on the retina and retinal cells. Moreover, we and others have demonstrated the in vitro induction of a corneal epithelial cell phenotype from pluripotent stem cells. These studies, however, have a single, tissue-specific focus and fail to reflect the complexity of whole eye development. Here we demonstrate the generation from human induced pluripotent stem cells of a self-formed ectodermal autonomous multi-zone (SEAM) of ocular cells. In some respects the concentric SEAM mimics whole-eye development because cell location within different zones is indicative of lineage, spanning the ocular surface ectoderm, lens, neuro-retina, and retinal pigment epithelium. It thus represents a promising resource for new and ongoing studies of ocular morphogenesis. The approach also has translational potential and to illustrate this we show that cells isolated from the ocular surface ectodermal zone of the SEAM can be sorted and expanded ex vivo to form a corneal epithelium that recovers function in an experimentally induced animal model of corneal blindness.

Sleep and mood disorders in dry eye disease and allied irritating ocular diseases.

PubMed

Ayaki, Masahiko; Kawashima, Motoko; Negishi, Kazuno; Kishimoto, Taishiro; Mimura, Masaru; Tsubota, Kazuo

2016-03-01

The aim of the present study was to evaluate sleep and mood disorders in patients with irritating ocular diseases. The study design was a cross-sectional/case-control study conducted in six eye clinics. Out of 715 outpatients diagnosed with irritating ocular surface diseases and initially enrolled, 301 patients with dry eye disease (DED) and 202 age-matched control participants with other ocular surface diseases were analyzed. The mean Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS) scores were 6.4 ± 3.2 and 11.1 ± 5.7 for severe DED (n = 146), 5.5 ± 3.3 and 9.8 ± 4.0 for mild DED (n = 155), 5.5 ± 3.1 and 9.5 ± 6.6 for chronic conjunctivitis (n = 124), and 5.0 ± 3.3 and 8.9 ± 5.3 for allergic conjunctivitis (n = 78). There were significant differences among these diagnostic groups for PSQI (P < 0.05). Regression analysis of patients with DED revealed the PSQI and HADS scores were significantly correlated with the severity of DED (P < 0.05). Our results demonstrate that sleep quality in patients with DED is significantly worse than in patients with other irritating ocular surface diseases and it is correlated with the severity of DED.

Episcleral, intrascleral, and suprachoroidal routes of ocular drug delivery - recent research advances and patents.

PubMed

Gilger, Brian C; Mandal, Abhirup; Shah, Sujay; Mitra, Ashim K

2014-01-01

Subconjunctival/episcleral, intrascleral, and suprachoroidal routes of drug delivery for treatment of posterior segment eye diseases have become more feasible and popular in the past few years. These routes have the advantage of bypassing the main barriers to topical drug penetration, the ocular surface epithelium, the conjunctivallymphatics, and in the case of deep intrascleral and suprachoroidial delivery, the sclera barrier. Many ocular drug delivery application devices, drug delivery methods, and therapeutics that have been developed for intravitreal use can also be used subconjunctivally, intrasclerally, and in the suprachoroidal space. Alternatively, site-specific devices, such microneedles, and therapeutics, such as hydrogel matrices, have been developed to enhance ocular drug delivery. This manuscript will review the recent research advances and patents on episcleral, intrascleral, and suprachoroidal routes of ocular drug delivery.

Nontuberculous Mycobacterial Ocular Infections: A Systematic Review of the Literature

PubMed Central

Kheir, Wajiha J.; Sheheitli, Huda; Abdul Fattah, Maamoun; Hamam, Rola N.

2015-01-01

Nontuberculous or atypical mycobacterial ocular infections have been increasing in prevalence over the past few decades. They are known to cause periocular, adnexal, ocular surface and intraocular infections and are often recalcitrant to medical therapy. These infections can potentially cause detrimental outcomes, in part due to a delay in diagnosis. We review 174 case reports and series on nontuberculous mycobacterial (NTM) ocular infections and discuss etiology, microbiology, risk factors, diagnosis, clinical presentation, and treatment of these infections. History of interventions, trauma, foreign bodies, implants, contact lenses, and steroids are linked to NTM ocular infections. Steroid use may prolong the duration of the infection and cause poorer visual outcomes. Early diagnosis and initiation of treatment with multiple antibiotics are necessary to achieve the best visual outcome. PMID:26106601

Corneal Epitheliopathy After Trauma by Fake Snow Powder in a 7-year-old Child

PubMed Central

Al-Amry, Mohammad A.; Al-Ghadeer, Huda A.

2016-01-01

Fake snow is a polymer of sodium polyacrylates used in games and celebrations. Despite the product leaflet that indicates safety, contact with the ocular surface can cause injury. We report a case of a child with corneal epitheliopathy due to a chemical burn injury after ocular surface contact with fake snow. The case was managed with epithelial debridement and a bandage contact lenses and topical antibiotics with complete resolution. PMID:27555717

Development of Causative Treatment Strategies for Lacrimal Gland Insufficiency by Tissue Engineering and Cell Therapy. Part 2: Reconstruction of Lacrimal Gland Tissue: What Has Been Achieved So Far and What Are the Remaining Challenges?

PubMed

Massie, Isobel; Dietrich, Jana; Roth, Mathias; Geerling, Gerd; Mertsch, Sonja; Schrader, Stefan

2016-10-01

The lacrimal gland is located in the upper temporal compartment of the orbita, and along with the ocular surface, eye lids, and sensory and motor nerves forms the lacrimal functional unit (LFU). The LFU is responsible for producing, distributing, and maintaining the tear film in order to maintain a smooth, moist, and regular ocular surface epithelium such that appropriate refractive properties are achieved and the eyeball is protected against dust, debris, and pathogens. If the main lacrimal gland is impaired (due to either disease or injury), this balance is disrupted, and severe quantitative dry eye syndrome (DES) can develop. DES treatments remain palliative, with the most commonly used therapies being based on tear substitution, tear retention, and control of inflammation on the ocular surface. Causative treatments such as salivary gland transplantation have shown to reduce symptoms in very severe cases, however can cause problems on the ocular surface due to different properties of saliva and tears. Therefore, causative approaches for treating DES by regeneration or reconstruction of lacrimal gland tissue depending on disease severity seem highly appealing. This article reviews current approaches for in vitro reconstruction of lacrimal gland tissue. Finally, the limitations that must be overcome before a new, tissue-engineered therapy may be delivered to clinic will be discussed.

α-Melanocyte-stimulating hormone ameliorates ocular surface dysfunctions and lesions in a scopolamine-induced dry eye model via PKA-CREB and MEK-Erk pathways.

PubMed

Ru, Yusha; Huang, Yue; Liu, Huijuan; Du, Juan; Meng, Zhu; Dou, Zexia; Liu, Xun; Wei, Rui Hua; Zhang, Yan; Zhao, Shaozhen

2015-12-21

Dry eye is a highly prevalent, chronic, and multifactorial disease that compromises quality of life and generates socioeconomic burdens. The pathogenic factors of dry eye disease (DED) include tear secretion abnormalities, tear film instability, and ocular surface inflammation. An effective intervention targeting the pathogenic factors is needed to control this disease. Here we applied α-Melanocyte-stimulating hormone (α-MSH) twice a day to the ocular surface of a scopolamine-induced dry eye rat model. The results showed that α-MSH at different doses ameliorated tear secretion, tear film stability, and corneal integrity, and corrected overexpression of proinflammatory factors, TNF-α, IL-1β, and IFN-γ, in ocular surface of the dry eye rats. Moreover, α-MSH, at 10(-4) μg/μl, maintained corneal morphology, inhibited apoptosis, and restored the number and size of conjunctival goblet cells in the dry eye rats. Mechanistically, α-MSH activated both PKA-CREB and MEK-Erk pathways in the dry eye corneas and conjunctivas; pharmacological blockade of either pathway abolished α-MSH's protective effects, suggesting that both pathways are necessary for α-MSH's protection under dry eye condition. The peliotropic protective functions and explicit signaling mechanism of α-MSH warrant translation of the α-MSH-containing eye drop into a novel and effective intervention to DED.

Xenogeneic Acellular Conjunctiva Matrix as a Scaffold of Tissue-Engineered Corneal Epithelium

PubMed Central

Zhao, Haifeng; Qu, Mingli; Wang, Yao; Wang, Zhenyu; Shi, Weiyun

2014-01-01

Amniotic membrane-based tissue-engineered corneal epithelium has been widely used in the reconstruction of the ocular surface. However, it often degrades too early to ensure the success of the transplanted corneal epithelium when treating patients with severe ocular surface disorders. In the present study, we investigated the preparation of xenogeneic acellular conjunctiva matrix (aCM) and evaluated its efficacy and safety as a scaffold of tissue-engineered corneal epithelium. Native porcine conjunctiva was decellularized with 0.1% sodium dodecyl sulfate (SDS) for 12 h at 37°C and sterilized via γ-irradiation. Compared with native conjunctiva, more than 92% of the DNA was removed, and more than 90% of the extracellular matrix components (glycosaminoglycan and collagen) remained after the decellularization treatment. Compared with denuded amniotic membrane (dAM), the aCM possessed favorable optical transmittance, tensile strength, stability and biocompatibility as well as stronger resistance to degradation both in vitro and in vivo. The corneal epithelial cells seeded on aCM formed a multilayered epithelial structure and endured longer than did those on dAM. The aCM-based tissue-engineered corneal epithelium was more effective in the reconstruction of the ocular surface in rabbits with limbal stem cell deficiency. These findings support the application of xenogeneic acellular conjunctiva matrix as a scaffold for reconstructing the ocular surface. PMID:25375996

α-Melanocyte-stimulating hormone ameliorates ocular surface dysfunctions and lesions in a scopolamine-induced dry eye model via PKA-CREB and MEK-Erk pathways

PubMed Central

Ru, Yusha; Huang, Yue; Liu, Huijuan; Du, Juan; Meng, Zhu; Dou, Zexia; Liu, Xun; Wei, Rui Hua; Zhang, Yan; Zhao, Shaozhen

2015-01-01

Dry eye is a highly prevalent, chronic, and multifactorial disease that compromises quality of life and generates socioeconomic burdens. The pathogenic factors of dry eye disease (DED) include tear secretion abnormalities, tear film instability, and ocular surface inflammation. An effective intervention targeting the pathogenic factors is needed to control this disease. Here we applied α-Melanocyte-stimulating hormone (α-MSH) twice a day to the ocular surface of a scopolamine-induced dry eye rat model. The results showed that α-MSH at different doses ameliorated tear secretion, tear film stability, and corneal integrity, and corrected overexpression of proinflammatory factors, TNF-α, IL-1β, and IFN-γ, in ocular surface of the dry eye rats. Moreover, α-MSH, at 10−4 μg/μl, maintained corneal morphology, inhibited apoptosis, and restored the number and size of conjunctival goblet cells in the dry eye rats. Mechanistically, α-MSH activated both PKA-CREB and MEK-Erk pathways in the dry eye corneas and conjunctivas; pharmacological blockade of either pathway abolished α-MSH’s protective effects, suggesting that both pathways are necessary for α-MSH’s protection under dry eye condition. The peliotropic protective functions and explicit signaling mechanism of α-MSH warrant translation of the α-MSH-containing eye drop into a novel and effective intervention to DED. PMID:26685899

Effects of the rigid gas permeable contact lense use on tear and ocular surface among keratoconus patients.

PubMed

Yuksel Elgin, Cansu; Iskeleli, Guzin; Aydin, Ovgu

2018-06-01

To investigate changes in tear and ocular surface of patients with keratoconus using rigid gas permeable contact lenses (RGPCL) and compare them against keratoconus patients who were not using lenses as well as a control group of healthy subjects. 24 keratoconus patients using RGPCL (Group 1) 22 patients who were not using lenses (Group 3) and 21 healthy subjects (Group 3) were included in the study. Subjective complaints about the subjects' eyes have been investigated using the ocular-surface disease index (OSDI). After the control of best-corrected visual acuity, anterior chamber and fundus examinations were performed. Schirmer (p-value=0.01) and tear break up mean comparison tests (p-value=0.002) revealed significant differences across different groups but tear osmolarity analysis did not (p-value >0.05). Oxford and OSDI scores were compatible with Schirmer and tear break up test comparisons. (for both p-value=0.001) Moreover, no statistical differences were seen in impression cytology measures between groups. (p-value >0.05) CONCLUSIONS: The erosion in the tear film stability is in line with the erosion in the ocular surface epithelium. Taking into account the statistical indifference between the impression cytology measures across groups, the break up time differences may be attributed to the collagen destruction in tear. Copyright © 2017 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Treatment of ocular rosacea: comparative study of topical cyclosporine and oral doxycycline.

PubMed

Arman, Aysegul; Demirseren, Duriye Deniz; Takmaz, Tamer

2015-01-01

To compare the effectiveness of topical cyclosporine A emulsion with that of oral doxycycline for rosacea associated ocular changes and dry eye complaints. One hundred and ten patients with rosacea were screened. Thirty-eight patients having rosacea associated eyelid and ocular surface changes and dry eye complaints were included in the study. Patients were randomly divided into two groups: nineteen patients were given topical cyclosporine twice daily and nineteen patients were given oral doxycycline 100 mg twice daily for the first month and once daily for the following two months. Symptom and sign scores, ocular surface disease index questionnarie and tear function tests were evaluated at baseline and monthly for 3mo. Three months after results were compared with that of baseline. Mean values of symptom, eyelid sign and corneal/conjunctival sign scores of each treatment group at baseline and 3mo after treatments were compared and both drugs were found to be effective on rosacea associated ocular changes (P<0.001). Cyclosporine was more effective in symptomatic relief and in the treatment of eyelid signs (P=0.01). There was statistically significant increase in the mean Schirmer score with anesthesia and tear break up time scores in the cyclosporine treatment group compared to the doxycycline treatment group (P<0.05). Cyclosporine as a topical drug can be used in the treatment of rosacea associated ocular complications because it is more effective than doxycycline. In addition ocular rosacea as a chronic disease requires long term treatment and doxycycline has various side effects limiting its long term usage.

Solitary Tracheobronchial Papilloma: Cytomorphology and ancillary studies with histologic correlation.

PubMed

Lang, Tee U; Khalbuss, Walid E; Monaco, Sara E; Pantanowitz, Liron

2011-03-03

Solitary tracheobronchial papilloma (STBP) is a rare benign tumor that primarily involves the tracheobronchial tree. Human papilloma virus (HPV) infection is associated with dysplasia and a high risk of carcinoma in these lesions. The cytomorphology of STBP is not well established in the literature. Our aim is to characterize the cytomorphologic features of STBP, with histologic correlation in a series of 6 patients - 4 males and 2 females - with a mean age of 67 years (range, 53-88 years). There were 5 biopsy-proven squamous papillomas and 1 glandular papilloma. On surgical biopsy, squamous papillomas exhibited cytological atypia (4 graded mild and 1 graded moderate with focal severe dysplasia), surface erosion, and inflammation. Cytology specimens available for review included a combination of 4 fine-needle aspirations (FNAs), 2 bronchoalveolar lavages and 2 (of 3) bronchial brushings. Cytologic findings associated with squamous papillomas included atypical squamous cells and rare squamous cell resembling koilocyte in 1 bronchial brushing. Sheets of squamous cells were identified in another specimen. Several cases had a prominent background of acute inflammation, and candida was present in 1 specimen. HPV in-situ hybridization was positive in 1 case and negative in 2 cases. A p16 immunocytochemical stain performed on 1 cell block was negative. In conclusion, although STBP is a rare neoplasm, these cases may be encountered in respiratory cytology samples. FNA of papillomas yields fewer lesional cells compared to exfoliative samples. These lesions may be mistaken in cytology specimens for squamous cell carcinoma, squamous-lined cavitary lesions, an infectious (fungal) process, reactive squamous metaplasia, or oral contamination.

The effects of 2% rebamipide ophthalmic solution on the tear functions and ocular surface of the superoxide dismutase-1 (sod1) knockout mice.

PubMed

Ohguchi, Takeshi; Kojima, Takashi; Ibrahim, Osama M; Nagata, Taeko; Shimizu, Takahiko; Shirasawa, Takuji; Kawakita, Tetsuya; Satake, Yoshiyuki; Tsubota, Kazuo; Shimazaki, Jun; Ishida, Susumu

2013-11-21

To investigate the efficacy of 2% rebamipide ophthalmic solution on the tear functions and ocular surface status of the superoxide dismutase-1(Sod1(-/-)) mice. Two percent Rebamipide ophthalmic solution was applied to 40-week-old male Sod1(-/-) and wild-type (WT) mice four times a day for 2 weeks. We examined the cytokine concentrations in the tear fluid (by CytoBead assay), tear film break-up time, amount of tear production, and expressions of mucins 1, 4, and 5AC, by RT-PCR. We also performed vital staining of the ocular surface, PAS staining for muc5AC, and immunohistochemical stainings for 4-hydroxy-2-nonenal (4-HNE), 8-hydroxy-2'-deoxyguanosine (8-OHdG), in the conjunctiva to compare the results before and after rebamipide instillations. The tear functions and ocular surface epithelial damage scores were significantly worse in the Sod1(-/-) than in the WT mice. Application of 2% rebamipide for 2 weeks significantly improved the tear film break-up time, the amount of tear production, and the corneal epithelial damage scores, which also significantly increased the conjunctival goblet cell density and muc5 mRNA expression, in the Sod1(-/-) mice. The mean IL-6, IL-17, TNF-α, and IFN-γ levels in the tear fluid were reduced significantly along with a significant decrease in the density of cells positive for 4-HNE and 8-OHdG in the conjunctiva. Two percent Rebamipide ophthalmic solution significantly improved the tear stability and corneal epithelial damage, and enhanced the expression of muc5 mRNA on the ocular surface. We also observed anti-inflammatory effects in the tear film together with antioxidative effects in the conjunctiva, suggesting the efficacy of rebamipide in age-related dry eye disease attributable to SOD1 knockout.

Comparing the Effects of Particulate Matter on the Ocular Surfaces of Normal Eyes and a Dry Eye Rat Model.

PubMed

Han, Ji Yun; Kang, Boram; Eom, Youngsub; Kim, Hyo Myung; Song, Jong Suk

2017-05-01

To compare the effect of exposure to particulate matter on the ocular surface of normal and experimental dry eye (EDE) rat models. Titanium dioxide (TiO2) nanoparticles were used as the particulate matter. Rats were divided into 4 groups: normal control group, TiO2 challenge group of the normal model, EDE control group, and TiO2 challenge group of the EDE model. After 24 hours, corneal clarity was compared and tear samples were collected for quantification of lactate dehydrogenase, MUC5AC, and tumor necrosis factor-α concentrations. The periorbital tissues were used to evaluate the inflammatory cell infiltration and detect apoptotic cells. The corneal clarity score was greater in the EDE model than in the normal model. The score increased after TiO2 challenge in each group compared with each control group (normal control vs. TiO2 challenge group, 0.0 ± 0.0 vs. 0.8 ± 0.6, P = 0.024; EDE control vs. TiO2 challenge group, 2.2 ± 0.6 vs. 3.8 ± 0.4, P = 0.026). The tear lactate dehydrogenase level and inflammatory cell infiltration on the ocular surface were higher in the EDE model than in the normal model. These measurements increased significantly in both normal and EDE models after TiO2 challenge. The tumor necrosis factor-α levels and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were also higher in the EDE model than in the normal model. TiO2 nanoparticle exposure on the ocular surface had a more prominent effect in the EDE model than it did in the normal model. The ocular surface of dry eyes seems to be more vulnerable to fine dust of air pollution than that of normal eyes.

Expression of Lipid Peroxidation Markers in the Tear Film and Ocular Surface of Patients with Non-Sjogren Syndrome: Potential Biomarkers for Dry Eye Disease.

PubMed

Choi, Won; Lian, Cui; Ying, Li; Kim, Ga Eon; You, In Cheon; Park, Soo Hyun; Yoon, Kyung Chul

2016-09-01

To investigate the expression of lipid peroxidation markers in the tear film and ocular surface and their correlation with disease severity in patients with dry eye disease. The concentrations of hexanoyl-lysine (HEL), 4-hydroxy-2-nonenal (HNE), and malondialdehyde (MDA) were measured with enzyme-linked immunosorbent assays in tears obtained from 44 patients with non-Sjogren syndrome dry eye and 33 control subjects. The correlations between the marker levels and the tear film and ocular surface parameters, including tear film break-up time (BUT), Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, corneal sensitivity, conjunctival goblet cell density, and symptom score, were analyzed. The expression of the lipid peroxidation markers HEL, 4-HNE, and MDA in the conjunctiva was evaluated using immunohistochemistry. The concentrations of HEL, 4-HNE, and MDA were 279.84 ± 69.98 nmol/L, 0.02 ± 0.01 μg/mL, and 3.80 ± 1.05 pmol/mg in control subjects and 283.21 ± 89.67 nmol/L (p = 0.97), 0.20 ± 0.03 μg/mL (p < 0.01), and 13.32 ± 4.03 pmol/mg (p < 0.01) in dry eye patients. 4-HNE and MDA levels significantly correlated with BUT, Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, conjunctival goblet cell density, and symptom score (p < 0.05), whereas HEL levels did not correlate with these parameters. Staining intensities for 4-HNE and MDA increased in dry eye patients. The expression of late lipid peroxidation markers, 4-HNE and MDA, increases in the tear film and ocular surface of patients with dry eye. The levels correlate with various tear film and ocular surface parameters and may reflect the severity of dry eye disease.

Corneal Expression of SLURP-1 by Age, Sex, Genetic Strain, and Ocular Surface Health

PubMed Central

Swamynathan, Sudha; Delp, Emili E.; Harvey, Stephen A. K.; Loughner, Chelsea L.; Raju, Leela; Swamynathan, Shivalingappa K.

2015-01-01

Purpose Although secreted Ly6/urokinase-type plasminogen activator receptor–related protein-1 (Slurp1) transcript is highly abundant in the mouse cornea, corresponding protein expression remains uncharacterized. Also, SLURP1 was undetected in previous tear proteomics studies, resulting in ambiguity about its baseline levels. Here, we examine mouse corneal Slurp1 expression in different sexes, age groups, strains, and health conditions, and quantify SLURP1 in human tears from healthy or inflamed ocular surfaces. Methods Expression of Slurp1 in embryonic day-13 (E13), E16, postnatal day-1 (PN1), PN10, PN20, and PN70 Balb/C, FVBN, C57Bl/6, and DBA/2J mouse corneas, Klf4Δ/ΔCE corneas with corneal epithelial–specific ablation of Klf4, migrating cells in wild-type corneal epithelial wound edge, and in corneas exposed to pathogen-associated molecular patterns (PAMPs) poly(I:C), zymosan-A, or Pam3Csk4 was examined by QPCR, immunoblots, and immunofluorescent staining. Human SLURP1 levels were quantified by ELISA in tears from 34 men and women aged 18 to 80 years. Results Expression of Slurp1, comparable in different strains and sexes, was low in E13, E16, PN1, and PN10 mouse corneas, and increased rapidly after eyelid opening in a Klf4-dependent manner. We found Slurp1 was downregulated in corneas exposed to PAMPs, and in migrating cells at the wound edge. Human SLURP1 expression, comparable in different sexes and age groups, was significantly decreased in tears from inflamed ocular surfaces (0.34%) than those from healthy individuals (0.77%). Conclusions These data describe the influence of age, sex, genetic background, and ocular surface health on mouse corneal expression of Slurp1, establish the baseline for human tear SLURP1 expression, and identify SLURP1 as a useful diagnostic and/or therapeutic target for inflammatory ocular surface disorders. PMID:26670825

Comparative effect of lens care solutions on blink rate, ocular discomfort and visual performance.

PubMed

Yang, Shun-nan; Tai, Yu-chi; Sheedy, James E; Kinoshita, Beth; Lampa, Matthew; Kern, Jami R

2012-09-01

To help maintain clear vision and ocular surface health, eye blinks occur to distribute natural tears over the ocular surface, especially the corneal surface. Contact lens wearers may suffer from poor vision and dry eye symptoms due to difficulty in lens surface wetting and reduced tear production. Sustained viewing of a computer screen reduces eye blinks and exacerbates such difficulties. The present study evaluated the wetting effect of lens care solutions (LCSs) on blink rate, dry eye symptoms, and vision performance. Sixty-five adult habitual soft contact lens wearers were recruited to adapt to different LCSs (Opti-free, ReNu, and ClearCare) in a cross-over design. Blink rate in pictorial viewing and reading (measured with an eyetracker), dry eye symptoms (measured with the Ocular Surface Disease Index questionnaire), and visual discrimination (identifying tumbling E) immediately before and after eye blinks were measured after 2 weeks of adaption to LCS. Repeated measures anova and mixed model ancova were conducted to evaluate effects of LCS on blink rate, symptom score, and discrimination accuracy. Opti-Free resulted in lower dry eye symptoms (p = 0.018) than ClearCare, and lower spontaneous blink rate (measured in picture viewing) than ClearCare (p = 0.014) and ReNu (p = 0.041). In reading, blink rate was higher for ClearCare compared to ReNu (p = 0.026) and control (p = 0.024). Visual discrimination time was longer for the control (daily disposable lens) than for Opti-Free (p = 0.007), ReNu (p = 0.009), and ClearCare (0.013) immediately before the blink. LCSs differently affected blink rate, subjective dry eye symptoms, and visual discrimination speed. Those with wetting agents led to significantly fewer eye blinks while affording better ocular comfort for contact lens wearers, compared to that without. LCSs with wetting agents also resulted in better visual performance compared to wearing daily disposable contact lenses. These presumably are because of improved tear film quality. © 2012 The College of Optometrists.

Evaluation of the inhalation toxicity of diethylethanolamine (DEEA) in rats.

PubMed

Hinz, J P; Thomas, J A; Ben-Dyke, R

1992-04-01

Diethylethanolamine (DEEA), an industrial anticorrosive additive, was evaluated in rats for its potential toxicity. A 2-week inhalation exposure to 10 ppm revealed no signs of toxicity. At 56 ppm, rats exhibited signs of nasal irritation and corneal opacities. Significant mortality (males, 90%; females, 50%) occurred at 301 ppm. Histopathology revealed inflammatory cell infiltrations of the nasal turbinate mucosa and squamous metaplasia after exposure to 56 ppm. In the 14-week subchronic study, rats were exposed to 0, 11, 25, or 76 ppm. During exposure to DEEA, transient signs of mild to moderate respiratory irritation (noises or rales) were observed with a frequency and severity that was dose dependent. These signs usually cleared within 1 hr post-exposure. However, at 76 ppm some rats continued to exhibit these respiratory signs overnight. There were no significant DEEA-induced changes in either blood chemistry or neurobehavioral parameters. Nasal cavities of rats exposed to 25 or 76 ppm revealed evidence of inflammatory cell infiltration, focal hyperplasia, and squamous metaplasia in the respiratory epithelium of the anterior nasal turbinates. Hypertrophic goblet cells, focal necrosis, and exudate in the nasal lumen were also seen at 76 ppm. DEEA vapors failed to produce persistent ocular or respiratory tract toxicity below 26 ppm. The no-observed-effect-level in this study was 10 ppm.

An atrophic, telangiectatic patch at the distal border of the tongue: a mucous membrane manifestation of xeroderma pigmentosum.

PubMed

Bologna, Sheyla Batista; Harumi Nakajima Teshima, Tathyane; Lourenço, Silvia Vanessa; Nico, Marcello Menta Simonsen

2014-01-01

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by clinical and cellular sensitivity, pigmentary changes, and early development of malignancies in sun-exposed mucocutaneous and ocular structures due to a defective ability to repair intracellular DNA damage. Individuals with XP also have a greater frequency of oral cancer, particularly squamous cell carcinoma of the anterior third of the tongue. The current study reports four cases of XP that exhibited a characteristic crescent-shaped, atrophic, telangiectatic area on the distal border of the tongue and correlates this lesion with the development of tumors at this site during follow-up. The tongue lesion was photographed and biopsied in the four patients. During routine follow-up visits, new biopsies were performed if additional tongue lesions were observed. The studied lesions were similar in the four patients. During follow-up, squamous cell carcinoma developed in one patient and pyogenic granuloma developed in three patients and was relapsing in one. The lesion remained stable in one patient during the study. The atrophic and telangiectatic patches probably occur because of chronic sun damage to the exposed portion of the tongue, and this area has a high predisposition for the development of benign and malignant tumors. © 2014 Wiley Periodicals, Inc.

Incorporation of liquid lipid in lipid nanoparticles for ocular drug delivery enhancement

NASA Astrophysics Data System (ADS)

Shen, Jie; Sun, Minjie; Ping, Qineng; Ying, Zhi; Liu, Wen

2010-01-01

The present work investigates the effect of liquid lipid incorporation on the physicochemical properties and ocular drug delivery enhancement of nanostructured lipid carriers (NLCs) and attempts to elucidate in vitro and in vivo the potential of NLCs for ocular drug delivery. The CyA-loaded or fluorescein-marked nanocarriers composed of Precifac ATO 5 and Miglyol 840 (as liquid lipid) were prepared by melting-emulsion technology, and the physicochemical properties of nanocarriers were determined. The uptake of nanocarriers by human corneal epithelia cell lines (SDHCEC) and rabbit cornea was examined. Ex vivo fluorescence imaging was used to investigate the ocular distribution of nanocarriers. The in vitro cytotoxicity and in vivo acute tolerance were evaluated. The higher drug loading capacity and improved in vitro sustained drug release behavior of lipid nanoparticles was found with the incorporation of liquid lipid in lipid nanoparticles. The uptake of nanocarriers by the SDHCEC was increased with the increase in liquid lipid loading. The ex vivo fluorescence imaging of the ocular tissues indicated that the liquid lipid incorporation could improve the ocular retention and penetration of ocular therapeutics. No alternation was macroscopically observed in vivo after ocular surface exposure to nanocarriers. These results indicated that NLC was a biocompatible and potential nanocarrier for ocular drug delivery enhancement.

Genome-Wide Association Study of Entropion Eyelid in Multiple Breeds of Sheep

USDA-ARS?s Scientific Manuscript database

Entropion is an inversion of the eyelid margin causing lashes or external hairs to rub against the ocular surface. If uncorrected, discomfort, ocular damage, increased eye infection rates, and potential blindness can occur. Entropion affects many mammalian species, can be expressed in both upper and...

Release of Membrane-associated Mucins from Ocular Surface Epithelia

PubMed Central

Blalock, Timothy D.; Spurr-Michaud, Sandra J.; Tisdale, Ann S.; Gipson, Ilene K.

2008-01-01

Purpose Three membrane-associated mucins (MAMs)—MUC1, MUC4 and MUC16—are expressed at the ocular surface epithelium. Soluble forms of MAMs are detected in human tears, but the mechanisms of their release from the apical cells are unknown. The purpose of this study was to identify physiologic agents that induce ocular surface MAM release. Methods An immortalized human corneal-limbal epithelial cell line (HCLE) expressing the same MAMs as native tissue was used. An antibody specific to MUC16’s cytoplasmic tail was developed to confirm that only the extracellular domain is released into the tear fluid or culture media. Effects of agents that have been shown to be present in tears or are implicated in release/shedding of MAMs in other epithelia (neutrophil elastase, tumor necrosis factor (TNF), TNF-α-converting enzyme, and matrix metalloproteinases-7 and –9) were assessed on HCLE cells. HCLE cell surface proteins were biotinylated to measure efficiency of induced MAM release and surface restoration. Effects of induced release on surface barrier function were measured by rose bengal dye penetrance. Results MUC16 in tears and in HCLE-conditioned medium lacked the cytoplasmic tail. TNF induced release of MUC1, MUC4, and MUC16 from the HCLE surface. Matrix metalloproteinase-7 and neutrophil elastase induced release of MUC16 but not MUC1 or MUC4. Neutrophil elastase removed 68% of MUC16—78% of which was restored to the HCLE cell surface 24 hours after release. Neutrophil elastase-treated HCLE cells showed significantly reduced rose bengal dye exclusion. Conclusions Results suggest that extracellular domains of MUC1, 4, and 16 can be released from the ocular surface by agents present in tears. Neutrophil elastase and TNF present in higher amounts in dry eye patients’ tears may cause MAM release—allowing rose bengal staining. PMID:18436821

Dry eye disease: pathophysiology, classification, and diagnosis.

PubMed

Perry, Henry D

2008-04-01

Dry eye disease (DED) is a multifactorial disorder of the tear film and ocular surface that results in eye discomfort, visual disturbance, and often ocular surface damage. Although recent research has made progress in elucidating DED pathophysiology, currently there are no uniform diagnostic criteria. This article discusses the normal anatomy and physiology of the lacrimal functional unit and the tear film; the pathophysiology of DED; DED etiology, classification, and risk factors; and DED diagnosis, including symptom assessment and the roles of selected diagnostic tests.

The Role of Medications in Causing Dry Eye

PubMed Central

Fraunfelder, Frederick T.; Sciubba, James J.; Mathers, William D.

2012-01-01

The purpose of this paper is to review the possible role of polypharmacy in causing dry eye disease (DED), reflecting the complex interactions and complications associated with the use of multiple systemic and topical ocular medications. The pharmacological, physiological, anatomical, and histological mechanisms causing dry mouth differ little from those causing dry eye. Oral polypharmacy is the most common cause of dry mouth, but has not been investigated as a cause of dry eye. Topical ocular polypharmacy has been shown to cause DED. Information on drugs that likely cause or aggravate DED and the controversial role of preservatives in topical ocular medications are examined. Systemic or topical ocular medications and preservatives used in topical ocular drugs may cause dry eye through the drug's therapeutic action, ocular surface effects, or preservatives, and the effects probably are additive. Long-term use of topical ocular medications, especially those containing preservatives such as BAK, may play an important role in DED and the role of polypharmacy needs further study. We review possible ways to decrease the risk of medication-related dry eye. PMID:23050121

γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL

PubMed Central

Kefala, Maria; Kottaridi, Christine; Spathis, Aris; Gouloumi, Alina-Roxani; Pouliakis, Abraham; Pappas, Asimakis; Sioulas, Vasileios; Chrelias, Charalambos; Karakitsos, Petros; Panayiotides, Ioannis

2017-01-01

Background γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas. Methods Immunostaining for phospho-γH2AX was performed in sections from histologically confirmed cervical SIL and carcinomas, as well as from normal cervices used as controls. In total, 275 cases were included in the study: 112 low grade SIL (LGSIL), 99 high grade SIL (HGSIL), 24 squamous cell carcinoma (SCC), 12 adenocarcinoma and 28 cervical specimens with no essential lesions. Correlation of histological grading, high risk vs. low risk HPV virus presence, activated vs. non-activated status (by high risk HPV mRNA expression) and γH2AX expression in both basal and surface segments of the squamous epithelium was performed. Results Gradual increase of both basal and surface γH2AX expression was noted up from normal cervices to LGSIL harboring a low risk HPV type, to LGSIL harboring a high risk virus at a non-activated state (p<0.05). Thereafter, both basal and surface γH2AX expression dropped in LGSIL harboring a high risk virus at an activated state and in HGSIL. Conclusions γH2AX could serve as a potential biomarker discriminating between LGSIL and HGSIL, as well as between LGSIL harboring high risk HPV at an activated state. PMID:28118377

Differential effect of rebamipide on transmembrane mucin biosynthesis in stratified ocular surface epithelial cells.

PubMed

Uchino, Yuichi; Woodward, Ashley M; Argüeso, Pablo

2016-12-01

Mucins are a group of highly glycosylated glycoproteins responsible for the protection of wet-surfaced epithelia. Recent data indicate that transmembrane mucins differ in their contribution to the protective function of the ocular surface, with MUC16 being the most effective barrier on the apical surface glycocalyx. Here, we investigated the role of the mucoprotective drug rebamipide in the regulation of transmembrane mucin biosynthesis using stratified cultures of human corneal and conjunctival epithelial cells. We find that the addition of rebamipide to corneal, but not conjunctival, epithelial cells increased MUC16 protein biosynthesis. Rebamipide did not affect the levels of MUC1, 4 and 20 compared to control. In these experiments, rebamipide had no effect on the expression levels of Notch intracellular domains, suggesting that the rebamipide-induced increase in MUC16 biosynthesis in differentiated corneal cultures is not regulated by Notch signaling. Overall these findings indicate that rebamipide induces the differential upregulation of MUC16 in stratified cultures of human corneal epithelial cells, which may have implications to the proper restoration of barrier function in ocular surface disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of magnetic field strength and receiver coil in ocular MRI: a phantom and patient study.

PubMed

Erb-Eigner, K; Warmuth, C; Taupitz, M; Willerding, G; Bertelmann, E; Asbach, P

2013-09-01

Generally, high-resolution MRI of the eye is performed with small loop surface coils. The purpose of this phantom and patient study was to investigate the influence of magnetic field strength and receiver coils on image quality in ocular MRI. The eyeball and the complex geometry of the facial bone were simulated by a skull phantom with swine eyes. MR images were acquired with two small loop surface coils with diameters of 4 cm and 7 cm and with a multi-channel head coil at 1.5 and 3 Tesla, respectively. Furthermore, MRI of the eye was performed prospectively in 20 patients at 1.5 Tesla (7 cm loop surface coil) and 3 Tesla (head coil). These images were analysed qualitatively and quantitatively and statistical significance was tested using the Wilcoxon-signed-rank test (a p-value of less than 0.05 was considered to indicate statistical significance). The analysis of the phantom images yielded the highest mean signal-to-noise ratio (SNR) at 3 Tesla with the use of the 4 cm loop surface coil. In the phantom experiment as well as in the patient studies the SNR was higher at 1.5 Tesla by applying the 7 cm surface coil than at 3 Tesla by applying the head coil. Concerning the delineation of anatomic structures no statistically significant differences were found. Our results show that the influence of small loop surface coils on image quality (expressed in SNR) in ocular MRI is higher than the influence of the magnetic field strength. The similar visibility of detailed anatomy leads to the conclusion that the image quality of ocular MRI at 3 Tesla remains acceptable by applying the head coil as a receiver coil. © Georg Thieme Verlag KG Stuttgart · New York.

Sutureless Fixation of Amniotic Membrane for Therapy of Ocular Surface Disorders

PubMed Central

Kotomin, Ilya; Valtink, Monika; Hofmann, Kai; Frenzel, Annika; Morawietz, Henning; Werner, Carsten; Funk, Richard H. W.; Engelmann, Katrin

2015-01-01

Amniotic membrane is applied to the diseased ocular surface to stimulate wound healing and tissue repair, because it releases supportive growth factors and cytokines. These effects fade within about a week after application, necessitating repeated application. Generally, amniotic membrane is fixed with sutures to the ocular surface, but surgical intervention at the inflamed or diseased site can be detrimental. Therefore, we have developed a system for the mounting of amniotic membrane between two rings for application to a diseased ocular surface without surgical intervention (sutureless amniotic membrane transplantation). With this system, AmnioClip, amniotic membrane can be applied like a large contact lens. First prototypes were tested in an experiment on oneself for wearing comfort. The final system was tested on 7 patients in a pilot study. A possible influence of the ring system on the biological effects of amniotic membrane was analyzed by histochemistry and by analyzing the expression of vascular endothelial growth factor-A (VEGF-A), hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF 2) and pigment epithelium-derived factor (PEDF) from amniotic membranes before and after therapeutic application. The final product, AmnioClip, showed good tolerance and did not impair the biological effects of amniotic membrane. VEGF-A and PEDF mRNA was expressed in amniotic membrane after storage and mounting before transplantation, but was undetectable after a 7-day application period. Consequently, transplantation of amniotic membranes with AmnioClip provides a sutureless and hence improved therapeutic strategy for corneal surface disorders. Trial Registration ClinicalTrials.gov NCT02168790 PMID:25955359

Chronic dry eye in photorefractive keratectomy and laser in situ keratomileusis: Manifestations, incidence, and predictive factors.

PubMed

Bower, Kraig S; Sia, Rose K; Ryan, Denise S; Mines, Michael J; Dartt, Darlene A

2015-12-01

To evaluate dry-eye manifestations after photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) and determine the incidence and predictive factors of chronic dry eye using a set of dry-eye criteria. Walter Reed Army Medical Center, Washington, DC, USA. Prospective, non-randomized clinical study. Dry-eye evaluation was performed before and after surgery. Main outcome measures included dry-eye manifestations, incidence, and predictive factors of chronic dry eye. This study comprised 143 active-duty U.S. Army personnel, ages 29.9 ± 5.2 years, with myopia or myopic astigmatism (manifest spherical equivalent -3.83 ± 1.96 diopters) having PRK or LASIK. Schirmer scores, corneal sensitivity, ocular surface staining, surface regularity index, and responses to dry-eye questionnaire significantly changed over time after PRK. After LASIK, significant changes were observed in tear breakup time, corneal sensitivity, ocular surface staining, and responses to questionnaire. Twelve months postoperatively, 5.0% of PRK and 0.8% of LASIK participants developed chronic dry eye. Regression analysis showed that pre-operatively lower Schirmer score will significantly influence development of chronic dry eye after PRK, whereas preoperatively, lower Schirmer score or higher ocular surface staining score will significantly influence the occurrence of chronic dry eye after LASIK. Chronic dry eye was uncommon after PRK and LASIK. Ocular surface and tear-film characteristics during pre-operative examination might help to predict chronic dry-eye development in PRK and LASIK. The authors have no financial interest in any product, drug, instrument, or equipment discussed in this manuscript. Copyright © 2015 ASCRS and ESCRS. All rights reserved.

Influenza Virus Respiratory Infection and Transmission Following Ocular Inoculation in Ferrets

PubMed Central

Belser, Jessica A.; Gustin, Kortney M.; Maines, Taronna R.; Pantin-Jackwood, Mary J.; Katz, Jacqueline M.; Tumpey, Terrence M.

2012-01-01

While influenza viruses are a common respiratory pathogen, sporadic reports of conjunctivitis following human infection demonstrates the ability of this virus to cause disease outside of the respiratory tract. The ocular surface represents both a potential site of virus replication and a portal of entry for establishment of a respiratory infection. However, the properties which govern ocular tropism of influenza viruses, the mechanisms of virus spread from ocular to respiratory tissue, and the potential differences in respiratory disease initiated from different exposure routes are poorly understood. Here, we established a ferret model of ocular inoculation to explore the development of virus pathogenicity and transmissibility following influenza virus exposure by the ocular route. We found that multiple subtypes of human and avian influenza viruses mounted a productive virus infection in the upper respiratory tract of ferrets following ocular inoculation, and were additionally detected in ocular tissue during the acute phase of infection. H5N1 viruses maintained their ability for systemic spread and lethal infection following inoculation by the ocular route. Replication-independent deposition of virus inoculum from ocular to respiratory tissue was limited to the nares and upper trachea, unlike traditional intranasal inoculation which results in virus deposition in both upper and lower respiratory tract tissues. Despite high titers of replicating transmissible seasonal viruses in the upper respiratory tract of ferrets inoculated by the ocular route, virus transmissibility to naïve contacts by respiratory droplets was reduced following ocular inoculation. These data improve our understanding of the mechanisms of virus spread following ocular exposure and highlight differences in the establishment of respiratory disease and virus transmissibility following use of different inoculation volumes and routes. PMID:22396651

Feasibility of quantitatively diagnosing cornea infection using Raman spectroscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Bai, Yanru; Chen, Keren; Mishra, Arti; Beuerman, Roger; Liu, Quan

2017-02-01

Ocular infection is a serious eye disease that could lead to blindness without prompt and proper treatment. In pathology, ocular infection is caused by microorganisms such as bacteria, fungi or viruses. The essential prerequisite for the optimal treatment of ocular infection is to identify the microorganism causing infection early as each type of microorganism requires a different therapeutic approach. The clinical procedure for identifying the microorganism species causing ocular infection includes Gram staining (for bacteria)/microscopy (for fungi) and the culture of corneal surface scraping, or aqueous and vitreous smear samples taken from the surface of infected eyes. The culture procedure is labor intensive and expensive. Moreover, culturing is time consuming, which usually takes a few days or even weeks. Such a long delay in diagnosis could result in the exacerbation of patients' symptoms, the missing of the optimal time frame for initiating treatment and subsequently the rising cost for disease management. Raman spectroscopy has been shown highly effective for non-invasive identification of both fungi and bacteria qualitatively. In this study, we investigate the feasibility of identifying the microorganisms of ocular infection and quantifying the concentrations using Raman spectroscopy by measuring not only gram negative and gram positive bacteria but also infected cornea. By applying a modified orthogonal projection approach, the relative concentration of each bacteria species could be quantified. Our results indicate the great potential of Raman spectroscopy as an alternative tool for non-invasive diagnosis of ocular infection and could play a significantly role in future ophthalmology.

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies.

PubMed

Mandal, Abhirup; Bisht, Rohit; Rupenthal, Ilva D; Mitra, Ashim K

2017-02-28

Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials. The mucoadhesive nature of these polymeric micelles results in enhanced contact with the ocular surface while their small size allows better tissue penetration. Most importantly, being highly water soluble, these polymeric micelles generate clear aqueous solutions which allows easy application in the form of eye drops without any vision interference. Enhanced stability, larger cargo capacity, non-toxicity, ease of surface modification and controlled drug release are additional advantages with polymeric micelles. Finally, simple and cost effective fabrication techniques render their industrial acceptance relatively high. This review summarizes structural frameworks, methods of preparation, physicochemical properties, patented inventions and recent advances of these micelles as effective carriers for ocular drug delivery highlighting their performance in preclinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Understanding the Presence and Roles of Ap4A (Diadenosine Tetraphosphate) in the Eye.

PubMed

Crooke, Almudena; Guzman-Aranguez, Ana; Carracedo, Gonzalo; de Lara, Maria J Perez; Pintor, Jesus

Diadenosine tetraphosphate abbreviated Ap 4 A is a naturally occurring dinucleotide, which is present in most of the ocular fluids. Due to its intrinsic resistance to enzyme degradation compared to mononucleotides, this molecule can exhibit profound actions on ocular tissues, including the ocular surface, ciliary body, trabecular meshwork, and probably the retina. The actions of Ap 4 A are mostly carried out by P2Y 2 receptors, but the participation of P2X2 and P2Y 6 in processes such as the regulation of intraocular pressure (IOP), together with the P2Y 2 , is pivotal. Beyond the physiological role, this dinucleotide can present on the ocular surface keeping a right production of tear secretion or regulating IOP. It is important to note that exogenous application of Ap 4 A to cells or animal models can significantly modify pathophysiological conditions and thus is an attractive therapeutic molecule. The ocular location where Ap 4 A actions have not been fully elucidated is in the retina. Although some analogues show interesting actions on pathological situations such as retinal detachment, little is known about the real effect of this dinucleotide, this being one of the challenges that require pursuing in the near future.

Comparing goblet cell densities in patients wearing disposable hydrogel contact lenses versus silicone hydrogel contact lenses in an extended-wear modality.

PubMed

Lievens, Christopher W; Connor, Charles G; Murphy, Heather

2003-10-01

The current study evaluates the response of the ocular surface to extended contact lens wear by comparing a new silicone hydrogel lens to an ACUVUE 2 lens. Twenty subjects with an average age of 28 years were randomly assigned to a fitting with ACUVUE 2 or PureVision lenses. Ocular surface assessment by impression cytology was performed at baseline and for the 6 months after initiation of lens wear. Although goblet cell density significantly increased with wear time, no statistically significant difference was observed between the contact lens groups. The average baseline goblet cell percentages were as follows: ACUVUE 2 group, 1.44; PureVision group, 1.11. The 6-month averages were as follows: ACUVUE 2 group, 3.16; PureVision group, 2.22. It appears that silicone hydrogel lenses may be slightly less irritating to the ocular surface than lenses not containing silicone. This could be a promising indicator for successful 30-day continuous wear.

Prevalencia de síntomas de enfermedad de la superficie ocular en pacientes que acuden a consulta oftalmológica.

PubMed

Garza-León, Manuel; Hernández-Quintela, Everardo; Cámara-Castillo, Héctor G; Parra-Collin, Paola de la; Covarrubias-Espinosa, Paola; Sánchez-Huerta, Valeria; Castillo-Ruiz, Alejandro Del; Rodríguez-Sixtos, Fernando; Pacheco-Patrón, Jorge; Ochoa-Tabares, Juan Carlos; Soto-Ortiz, Karina; Hernández-Olguin, Karen

2017-01-01

To determine the prevalence of symptoms of ocular surface disease (OSDI) surface disease and its relationship with associated risk factors in patients of ophthalmic practices using OSDI questionnaire. A cross-sectional survey was conducted Between September and December 2014 to assess the prevalence and risk factors for OSDI. The OSDI average value was 40.46 ± 23.62 points, with 86.4% of patients (1967) having a OSDI score higher than 12 points. Women had OSDI symptoms more frequently than men (odds ratio: 1.17; 95% confidence interval: 1.08-1.28) and higher OSDI score (42.12 ± 24.03 vs. 38.01 ± 22.81 points). Patients without disease were younger than the patients with severe disease (45.30 ± 18.32 vs. 50.62 ± 18.86). Ophthalmological patients have a prevalence of 80.4% of OSDI. Female and older age was associated with ocular surface disease. Copyright: © 2017 SecretarÍa de Salud

Altered Mucin and Glycoprotein Expression in Dry Eye Disease.

PubMed

Stephens, Denise N; McNamara, Nancy A

2015-09-01

Mucins are among the many important constituents of a healthy tear film. Mucins secreted and/or associated with conjunctival goblet cells, ocular mucosal epithelial cells, and the lacrimal gland must work together to create a stable tear film. Although many studies have explored the mechanism(s) whereby mucins maintain and protect the ocular surface, the effects of dry eye on the structure and function of ocular mucins are unclear. Here, we summarize current findings regarding ocular mucins and how they are altered in dry eye. We performed a literature review of studies exploring the expression of mucins produced and/or associated with tissues that comprise the lacrimal functional unit and how they are altered in dry eye. We also summarize new insights on the immune-mediated effects of aqueous tear deficiency on ocular surface mucins that we discovered using a mouse model of dry eye. Although consistent decreases in MUC5AC and altered expression of membrane-bound mucins have been noted in both Sjögren and non-Sjögren dry eye, many reports of altered mucins in dry eye are contradictory. Mechanistic studies, including our own, suggest that changes in the glycosylation of mucins rather than the proteins themselves may occur as the direct result of local inflammation induced by proinflammatory mediators, such as interleukin-1. Altered expression of ocular mucins in dry eye varies considerably from study to study, likely attributed to inherent difficulties in analyzing small-volume tear samples, as well as differences in tear collection methods and disease severity in dry eye cohorts. To better define the functional role of ocular mucin glycosylation in the pathogenesis of dry eye disease, we propose genomic and proteomic studies along with biological pathway analysis to reveal novel avenues for exploration.

Efficacy and safety of two new formulations of artificial tears in subjects with dry eye disease: a 3-month, multicenter, active-controlled, randomized trial

PubMed Central

Simmons, Peter A; Liu, Haixia; Carlisle-Wilcox, Cindy; Vehige, Joseph G

2015-01-01

Purpose To evaluate and compare the efficacy and safety of two investigational artificial tear formulations (CHO-1 and CHO-2) containing carmellose sodium, hyaluronic acid at different concentrations, and osmoprotectants, with a standard carmellose sodium-containing formulation (Refresh Tears [RT]) in the treatment of dry eye disease. Subjects and methods In this 3-month, double-masked, multicenter study, subjects (n=305) were randomized 1:1:1 to receive CHO-1, CHO-2, or RT, used as needed but at least twice daily. The primary endpoint was change in ocular surface disease index (OSDI) score from baseline to day 90. Other key outcomes included symptoms evaluated on a visual analog scale, corneal and conjunctival staining, and adverse events. Results OSDI scores and dry eye symptoms showed a rapid and sustained reduction from baseline in each group. Both CHO-1 and CHO-2 met the primary efficacy endpoint of noninferiority to RT in day 90 OSDI score change from baseline. OSDI ocular symptoms subscale improved more with CHO-1 than CHO-2 (P=0.048). In subjects with clinically relevant baseline ocular surface staining (>14 total score of a maximum of 55), day 90 improvements were greater with CHO-1 and CHO-2 than RT (P≤0.044). Day 90 improvements in OSDI ocular symptoms subscale scores were also greater with CHO-1 than RT (P<0.007) in subjects with clinically relevant ocular staining. All treatments were well tolerated. Conclusion Both combination artificial tear formulations were efficacious and well tolerated in subjects with dry eye. CHO-1 demonstrated the best performance in improving ocular symptoms and reducing ocular staining in this heterogeneous study population. PMID:25931807

Will vaccination against human papillomavirus prevent eye disease? A review of the evidence.

PubMed

Hughes, D S; Powell, N; Fiander, A N

2008-04-01

The role of human papillomavirus (HPV) infection in eye disease is controversial. However, a recent case illustrates the possible role of HPV in conjunctival squamous carcinoma and the potentially devastating effects of this disease. The development of two vaccines to prevent infection with HPV types most commonly associated with anogenital cancers has led to debate about the pros and cons of a national immunisation programme to prevent cervical cancer. The introduction of such a vaccination programme may have an additional beneficial effect on the occurrence of some head and neck, including ocular, cancers. This review discusses the nature of papillomaviruses, mechanisms of infection and carcinogenesis, the possible role of HPV in eye disease, and finally the likely impact of the new prophylactic vaccines.

Regulation of ocular surface inflammation by prostaglandin E receptor subtype EP3.

PubMed

Ueta, Mayumi

2010-11-01

We first investigated whether the prostaglandin (PG) E2-PGE receptor subtype EP3 axis regulates the development of murine experimental allergic conjunctivitis because it has been reported that this pathway negatively regulates allergic reactions in a murine allergic asthma model. We observed that EP3 is constitutively expressed in mice conjunctival epithelium. EP3 knockout mice demonstrated significantly increased eosinophil infiltration in conjunctiva after ragweed challenge compared with wild-type mice. Consistently, significantly higher expression of eotaxin-1 messenger RNA was observed in Ptger3-/- mice. Conversely, treatment of wild-type mice with an EP3-selective agonist significantly decreased eosinophil infiltration, which was blunted in Ptger3-/- mice. Expression of cyclooxygenase-2 and PGE synthases was upregulated and PGE2 content increased in the eyelids after ragweed challenge. These data suggest that PGE2 acts on EP3 in the conjunctival epithelium and downregulates the progression of experimental allergic conjunctivitis. We next examined and compared the expression of EP3 in human conjunctival epithelium in various ocular surface diseases. Human conjunctival epithelium expressed EP3-specific messenger RNA and EP3 protein. Although we could clearly find positive signals in the conjunctival epithelium from patients with noninflammatory ocular surface diseases such as conjunctivochalasis and pterygium, we could not find positive signals in that from those with inflammatory disorders such as Stevens-Johnson syndrome and ocular cicatricial pemphigoid. Likewise, expression of the PGE receptor subtype EP4 was clearly found in the conjunctival epithelium from patients with conjunctivochalasis and pterygium but not from patients with Stevens-Johnson syndrome and ocular cicatricial pemphigoid.

Silk film biomaterials for ocular surface repair

NASA Astrophysics Data System (ADS)

Lawrence, Brian David

Current biomaterial approaches for repairing the cornea's ocular surface upon injury are partially effective due to inherent material limitations. As a result there is a need to expand the biomaterial options available for use in the eye, which in turn will help to expand new clinical innovations and technology development. The studies illustrated here are a collection of work to further characterize silk film biomaterials for use on the ocular surface. Silk films were produced from regenerated fibroin protein solution derived from the Bombyx mori silkworm cocoon. Methods of silk film processing and production were developed to produce consistent biomaterials for in vitro and in vivo evaluation. A wide range of experiments was undertaken that spanned from in vitro silk film material characterization to in vivo evaluation. It was found that a variety of silk film properties could be controlled through a water-annealing process. Silk films were then generated that could be use in vitro to produce stratified corneal epithelial cell sheets comparable to tissue grown on the clinical standard substrate of amniotic membrane. This understanding was translated to produce a silk film design that enhanced corneal healing in vivo on a rabbit injury model. Further work produced silk films with varying surface topographies that were used as a simplified analog to the corneal basement membrane surface in vitro. These studies demonstrated that silk film surface topography is capable of directing corneal epithelial cell attachment, growth, and migration response. Most notably epithelial tissue development was controllably directed by the presence of the silk surface topography through increasing cell sheet migration efficiency at the individual cellular level. Taken together, the presented findings represent a comprehensive characterization of silk film biomaterials for use in ocular surface reconstruction, and indicate their utility as a potential material choice in the development of innovative procedures and technologies for corneal repair.

Transcription, Translation, and Function of Lubricin, a Boundary Lubricant, at the Ocular Surface

PubMed Central

Schmidt, Tannin A.; Sullivan, David A.; Knop, Erich; Richards, Stephen M.; Knop, Nadja; Liu, Shaohui; Sahin, Afsun; Darabad, Raheleh Rahimi; Morrison, Sheila; Kam, Wendy R.; Sullivan, Benjamin D.

2013-01-01

Importance Lubricin may be an important barrier to the development of corneal and conjunctival epitheliopathies that may occur in dry eye disease and contact lens wear. Objective To test the hypotheses that lubricin (ie, proteoglycan 4 [PRG4]), a boundary lubricant, is produced by ocular surface epithelia and acts to protect the cornea and conjunctiva against significant shear forces generated during an eyelid blink and that lubricin deficiency increases shear stress on the ocular surface and promotes corneal damage. Design, Setting, and Participants Human, porcine, and mouse tissues and cells were processed for molecular biological, immunohistochemical, and tribological studies, and wild-type and PRG4 knockout mice were evaluated for corneal damage. Results Our findings demonstrate that lubricin is transcribed and translated by corneal and conjunctival epithelial cells. Lubricin messenger RNA is also present in lacrimal and meibomian glands, as well as in a number of other tissues. Absence of lubricin in PRG4 knockout mice is associated with a significant increase in corneal fluorescein staining. Our studies also show that lubricin functions as an effective friction-lowering boundary lubricant at the human cornea-eyelid interface. This effect is specific and cannot be duplicated by the use of hyaluronate or bovine serum albumin solutions. Conclusions and Relevance Our results show that lubricin is transcribed, translated, and expressed by ocular surface epithelia. Moreover, our findings demonstrate that lubricin presence significantly reduces friction between the cornea and conjunctiva and that lubricin deficiency may play a role in promoting corneal damage. PMID:23599181

Transcription, translation, and function of lubricin, a boundary lubricant, at the ocular surface.

PubMed

Schmidt, Tannin A; Sullivan, David A; Knop, Erich; Richards, Stephen M; Knop, Nadja; Liu, Shaohui; Sahin, Afsun; Darabad, Raheleh Rahimi; Morrison, Sheila; Kam, Wendy R; Sullivan, Benjamin D

2013-06-01

Lubricin may be an important barrier to the development of corneal and conjunctival epitheliopathies that may occur in dry eye disease and contact lens wear. To test the hypotheses that lubricin (ie, proteoglycan 4 [PRG4 ]), a boundary lubricant, is produced by ocular surface epithelia and acts to protect the cornea and conjunctiva against significant shear forces generated during an eyelid blink and that lubricin deficiency increases shear stress on the ocular surface and promotes corneal damage. Human, porcine, and mouse tissues and cells were processed for molecular biological, immunohistochemical, and tribological studies, and wild-type and PRG4 knockout mice were evaluated for corneal damage. Our findings demonstrate that lubricin is transcribed and translated by corneal and conjunctival epithelial cells. Lubricin messenger RNA is also present in lacrimal and meibomian glands, as well as in a number of other tissues. Absence of lubricin in PRG4 knockout mice is associated with a significant increase in corneal fluorescein staining. Our studies also show that lubricin functions as an effective friction-lowering boundary lubricant at the human cornea-eyelid interface. This effect is specific and cannot be duplicated by the use of hyaluronate or bovine serum albumin solutions. Our results show that lubricin is transcribed, translated, and expressed by ocular surface epithelia. Moreover, our findings demonstrate that lubricin presence significantly reduces friction between the cornea and conjunctiva and that lubricin deficiency may play a role in promoting corneal damage.

Ocular surface changes following oral anticholinergic use for overactive bladder.

PubMed

Sekeroglu, Mehmet Ali; Hekimoglu, Emre; Tasci, Yasemin; Dolen, Ismail; Arslan, Umut

2016-09-01

To investigate the effect of oral solifenacin succinate on Schirmer I test results, tear break-up time (TBUT) and Ocular Surface Disease Index (OSDI) scores in overactive bladder (OAB) patients and to compare these results with those of healthy control subjects. The female OAB patients who were prescribed oral solifenacin succinate 5 mg/day (Group I, N = 80) and age-matched healthy female subjects (Group II, N = 40) were recruited for the study and underwent ophthalmological examination prior to oral treatment and after 4 weeks. They completed the OSDI questionnaire and underwent ocular surface tests including Schirmer I test and TBUT. The statistical analysis of the Schirmer I test and TBUT revealed no significant difference between the baseline and 4th week values in both groups (Group I, p = 0.506 and p = 0.070 consecutively) (Group II, p = 0.810 and p = 0.823 consecutively). OSDI scores were found to be significantly increased in group I (21.8 ± 4.2 vs 23.1 ± 4.6, p = 0.020) and remained unchanged in group II (20.5 ± 7.0 vs 20.7 ± 7.0, p = 0.805). Short-term solifenacin succinate treatment has no effect on the Schirmer I test results and TBUT, but ocular surface symptoms appeared to be exacerbated in respect with increased OSDI scores. However, the clinical significance needs to be further evaluated with larger studies.

Ocular Surface Disease in Glaucoma: Effect of Polypharmacy and Preservatives.

PubMed

Ramli, Norlina; Supramaniam, Gowri; Samsudin, Amir; Juana, Azida; Zahari, Mimiwati; Choo, May May

2015-09-01

To evaluate the prevalence of ocular surface disease (OSD) in glaucoma and nonglaucoma subjects using different clinical tests and to determine the effect of number of antiglaucoma medications and preservatives on OSD. This is a cross-sectional, case-comparison study at the Eye Clinic of the University of Malaya Medical Centre, Malaysia, between June 2012 and January 2013. Glaucoma subjects (n = 105) using topical antiglaucoma medications were compared with control subjects (n = 102) who were not on any topical medications. The presence of OSD was assessed using the tear film breakup time (TBUT) test, corneal staining, Schirmer test, and Ocular Surface Disease Index (OSDI) questionnaire grading. The prevalence of OSD varied from 37 to 91% in the glaucoma group, depending on the type of clinical test. More subjects in the glaucoma group had corneal staining (63% vs. 36%, p = 0.004), abnormal Schirmer tests (39% vs. 25%, p = 0.049), and moderate OSDI symptoms (17% vs. 7%, p = 0.028). The percentage with abnormal TBUT increased with higher numbers of topical medications and was high with both benzalkonium chloride-containing and preservative-free eye drops (90% and 94%, respectively, both p < 0.001). Benzalkonium chloride was associated with a nearly three times higher odds ratio of showing abnormal OSDI. Ocular surface disease is common in those using topical antiglaucoma medications. Abnormal TBUT is associated with increasing number of eye drops and benzalkonium chloride-containing eye drops, although this also occurs with the use of preservative-free eye drops.

Ocular surface infections in northeastern state of malaysia: a 10-year review of bacterial isolates and antimicrobial susceptibility.

PubMed

Rahman, Zaidah A; Harun, Azian; Hasan, Habsah; Mohamed, Zeehaida; Noor, Siti S Md; Deris, Zakuan Z; Ismail, Nabilah; Hassan, Asma S; Ahmad, Fadzhilah; Yaakub, Azhany

2013-09-01

Ocular surface infections that include infections of conjunctiva, adnexa, and cornea have the potential risk of causing blindness within a given population. Empirical antibiotic therapy is usually initiated based on epidemiological data of common causative agents. Thus, the aims of this study were to determine the bacterial agents and their susceptibility patterns of isolates from ocular surface specimens in our hospital. This is a retrospective analysis and records of bacterial isolates from ocular surface specimens in Hospital Universiti Sains Malaysia from January 2001 to December 2010 were examined. Specimens were processed according to standard laboratory procedures. Antimicrobial susceptibility testing was conducted based on Clinical and Laboratory Standards Institute recommendations. Only single, nonrepetitive isolates were included in the analysis. A total of 1,267 isolates were obtained during the study period, which comprised Staphylococcus aureus (n = 299, 23.6%), Pseudomonas aeruginosa (n = 194, 15.3%), Streptococcus pneumoniae (n = 108, 8.5%), Haemophilus influenzae (n = 100, 7.9%), Haemophilus parainfluenzae (n = 84, 6.6%), and Enterobacter spp. (n = 81, 6.4%). Fungi contributed to 4.4% of the total isolates. The antimicrobial susceptibility testing demonstrated that gram-positive bacteria were generally resistant to gentamicin (19%-57%), whereas gram-negative bacteria were resistant to chloramphenicol (27%-58%). Based on the above results, knowledge of the initial Gram stain findings is imperative before the commencement of empirical antibiotic therapy. Therefore, a simple Gram staining for all eye specimens is highly recommended.

7-Hydroxystaurosporine and Irinotecan Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors or Triple Negative Breast Cancer (Currently Accruing Only Triple-negative Breast Cancer Patients Since 6/8/2007)

ClinicalTrials.gov

2013-09-27

Advanced Adult Primary Liver Cancer; Carcinoma of the Appendix; Estrogen Receptor-negative Breast Cancer; Extensive Stage Small Cell Lung Cancer; Gastrointestinal Stromal Tumor; HER2-negative Breast Cancer; Metastatic Gastrointestinal Carcinoid Tumor; Ovarian Sarcoma; Ovarian Stromal Cancer; Progesterone Receptor-negative Breast Cancer; Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Adult Primary Liver Cancer; Recurrent Anal Cancer; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Borderline Ovarian Surface Epithelial-stromal Tumor; Recurrent Breast Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Endometrial Carcinoma; Recurrent Esophageal Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Prostate Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Recurrent Small Cell Lung Cancer; Recurrent Small Intestine Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Small Intestine Adenocarcinoma; Small Intestine Leiomyosarcoma; Small Intestine Lymphoma; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Anal Cancer; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Borderline Ovarian Surface Epithelial-stromal Tumor; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Endometrial Carcinoma; Stage IV Esophageal Cancer; Stage IV Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IV Gastric Cancer; Stage IV Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Prostate Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Stage IVA Cervical Cancer; Stage IVB Cervical Cancer; Triple-negative Breast Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer; Unspecified Adult Solid Tumor, Protocol Specific; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Skin cancer in black patients.

PubMed

Fleming, I D; Barnawell, J R; Burlison, P E; Rankin, J S

1975-03-01

Skin cancer is rare in black patients. The clinical course and pathology of 58 cases are presented and reviewed. These include 38 squamous cell carcinomas, 13 malignant melanomas, and 7 basal cell carcinomas. Sixty-one percent of the squamous cell carcinomas developed in unexposed areas, with sunlight exposure apparently not being an important etiologic factor. Forty-one percent of the squamous cell carcinomas had predisposing factors such as burn scars or chronic infection. Squamous cell carcinoma in black patients is an aggressive disease, with 29% developing regional lymph node metastasis, and a mortality of 29%. Malignant melanomas occurred most frequently on the plantar surface of the foot (76%). Melanoma is also a virulent tumor in black patients, with 11 of 13 patients developing lymph node metastasis and only 2 patients surviving. Skin cancer in black patients presents a very different clinical picture than that seen in white patients. It is important that these factors be considered when planning therapy.

Ocular Adverse Events Associated with Antibody–Drug Conjugates in Human Clinical Trials

PubMed Central

Miller, Paul E.; Mannis, Mark J.

2015-01-01

Abstract This article reviews ocular adverse events (AEs) reported in association with administration of antibody–drug conjugates (ADCs) in human clinical trials. References reporting ocular toxicity or AEs associated with ADCs were collected using online publication searches. Articles, abstracts, or citations were included if they cited ocular toxicities or vision-impairing AEs with a confirmed or suspected association with ADC administration. Twenty-two references were found citing ocular or vision-impairing AEs in association with ADC administration. All references reported use of ADCs in human clinical trials for treatment of various malignancies. The molecular target and cytotoxic agent varied depending on the ADC used. Ocular AEs affected a diversity of ocular tissues. The most commonly reported AEs involved the ocular surface and included blurred vision, dry eye, and corneal abnormalities (including microcystic corneal disease). Most ocular AEs were not severe (≤ grade 2) or dose limiting. Clinical outcomes were not consistently reported, but when specified, most AEs improved or resolved with cessation of treatment or with ameliorative therapy. A diverse range of ocular AEs are reported in association with administration of ADCs for the treatment of cancer. The toxicologic mechanism(s) and pathogenesis of such events are not well understood, but most are mild in severity and reversible. Drug development and medical professionals should be aware of the clinical features of these events to facilitate early recognition and intervention in the assessment of preclinical development programs and in human clinical trials. PMID:26539624

Expression of Ulex europaeus agglutinin I lectin-binding sites in squamous cell carcinomas and their absence in basal cell carcinomas. Indicator of tumor type and differentiation.

PubMed

Heng, M C; Fallon-Friedlander, S; Bennett, R

1992-06-01

Lectins bind tightly to carbohydrate moieties on cell surfaces. Alterations in lectin binding have been reported to accompany epidermal cell differentiation, marking alterations in membrane sugars during this process. The presence of UEA I (Ulex europaeus agglutinin I) L-fucose-specific lectin-binding sites has been used as a marker for terminally differentiated (committed) keratinocytes. In this article, we report the presence of UEA-I-binding sites on squamous keratinocytes of well-differentiated squamous cell carcinomas, with patchy loss of UEA I positivity on poorly differentiated cells of squamous cell carcinomas, suggesting a possible use for this technique in the rapid assessment of less differentiated areas within the squamous cell tumor. The absence of UEA-I-binding sites on basal cell carcinomas may be related to an inability of cells comprising this tumor to convert the L-D-pyranosyl moiety on basal cells to the L-fucose moiety, resulting in an inability of basal cell carcinoma cell to undergo terminal differentiation into a committed keratinocyte.

Meibomian gland dysfunction and ocular discomfort in video display terminal workers.

PubMed

Fenga, C; Aragona, P; Cacciola, A; Spinella, R; Di Nola, C; Ferreri, F; Rania, L

2008-01-01

Meibomian gland dysfunction (MGD) is one of the most common ocular disorders encountered in clinical practice. The clinical manifestations of MGD are related to the changes in the tear film and ocular surface with symptoms of ocular discomfort. In recent years, many surveys have evaluated symptoms associated with the use of Video Display Terminals (VDT), and VDT use is recognized as a risk factor for eye discomfort. The aim of the present study was to determine if the presence of MGD contributes to the signs and symptoms of ocular discomfort during the use of VDT. In course of a routine health surveillance programme, a group of 70 subjects fulfilled the inclusion criteria and responded to a questionnaire about symptoms of ocular discomfort. The following ocular tests were performed: tear break-up time, fluorescein corneal stain, and basal tear secretion test. A total of 52 subjects out of 70 (74.3%) had MGD. A statistically significant correlation between the symptoms of ocular discomfort and hours spent on VDT work was observed in the total population (r=0.358; P=0.002; 95% CI 0.13-0.54) and in the group of subjects with MGD (r=0.365; P=0.009; 95% CI 0.103-0.58). Such correlation was not shown in subjects without MGD. The high prevalence of MGD among the subjects with symptoms of ocular discomfort suggests that this diagnosis should be considered when occupational health practitioners encounter ocular complaints among VDT operators. It appears that MGD can contribute to the development of ocular discomfort in VDT operators.

[Novel current and future therapy options for treatment of dry eye disease].

PubMed

Messmer, E M

2018-02-01

Dry eye disease was redefined by the dry eye workshop (DEWS II) in May 2017. According to the new definition "dry eye is a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film and accompanied by ocular symptoms". The current definition encompasses etiological factors, such as instability and hyperosmolarity of the tear film, ocular surface inflammation and damage as well as a new aspect compared to the former definition, neurosensory abnormalities. Recent and future therapeutic options for dry eye focus on treatment of the aforementioned pathogenetic events. New tear substitutes, medications and devices to stimulate tear production, innovative anti-inflammatory treatment, medications to influence corneal innervation and new methods for treatment of Meibomian gland dysfunction are already available or will be available in the near future.

Ocular manifestations of rheumatoid arthritis and their correlation with anti-cyclic citrullinated peptide antibodies.

PubMed

Vignesh, Ammapati Paul Pandian; Srinivasan, Renuka

2015-01-01

To study the ocular manifestations of rheumatoid arthritis and to correlate the role of anti-cyclic citrullinated peptide antibody (anti-CCP antibody) with the ocular manifestations. Three-hundred and ninety-two eyes of the 196 rheumatoid arthritis patients who attended the ophthalmology outpatient department underwent a detailed ocular examination using slit lamp biomicroscopy and ophthalmoscopy. The tear function of all the patients was assessed using Schirmer's test, tear film break-up time and ocular surface staining. The anti-CCP antibody titers for all the rheumatoid arthritis patients were estimated using enzyme-linked immunosorbent assay tests. Seventy-seven patients (135 eyes, 39%) out of the 196 patients studied had ocular manifestations typical of rheumatoid arthritis. Dry eye was the most common manifestation (28%, 54 patients). Of the patients, 78% was females (60 patients). The mean duration of rheumatoid arthritis in patients with ocular manifestations was 5.4±2.7 years and without ocular manifestations was 2.1±1.6years. Three percent of the patients had episcleritis (six patients). Scleritis was present in 2% of the patients (four patients). Peripheral ulcerative keratitis and sclerosing keratitis was present in 1% of the population each (two patients each). Eighty-five percent (66 patients) had bilateral manifestations 15% (eleven patients) had unilateral manifestations. There was a strong association between the presence of anti-CCP antibodies and ocular manifestations of rheumatoid arthritis which was shown by the statistically significant P-value of <0.0001. Ocular manifestations are a significant part of the extra-articular manifestation of rheumatoid arthritis. Dry eye was the most common ocular manifestation. There was a statistically significant association between the presence of anti-CCP antibodies specific to rheumatoid arthritis and the ocular manifestations.

Periocular Skin Cancer in Solid Organ Transplant Recipients.

PubMed

Perry, Julian D; Polito, Sara C; Chundury, Rao V; Singh, Arun D; Fritz, Michael A; Vidimos, Allison T; Gastman, Brian R; Koyfman, Shlomo A

2016-01-01

To determine the proportion of solid organ transplant recipients developing periocular nonmelanoma skin cancer and to describe the morbidity of these cancers in transplant recipients. Cohort study. Consecutive patients undergoing solid organ transplantation at the Cleveland Clinic between 1990 and 2008. The charts of all patients receiving a solid organ transplant from 1990-2008 evaluated in the dermatology department for a subsequent biopsy-proven head and neck malignancy through April 2015 were reviewed. Patients with a periocular region nonmelanoma skin cancer (NMSC) or a nonperiocular NMSC causing a complication requiring eyelid surgery were included. Charts were reviewed for demographic data; transplant date, type, and source; immunosuppressive agents received at diagnosis; and type of NMSC, number of nonperiocular NMSCs, ophthalmologic findings, and periocular sequelae after the repair. Primary outcome measures included the type, location, final defect size, tumor-node-metastasis classification, presence of perineural invasion, and reconstruction technique(s) used for each periocular NMSC. Secondary outcome measures included the type and treatment of ocular sequelae due to nonperiocular facial NMSC. A total of 3489 patients underwent solid organ transplantation between 1990 and 2008. Of these, 420 patients were evaluated in the dermatology clinic for biopsy-proven NMSC of the head and neck during the study period, and 11 patients (15 malignancies) met inclusion criteria. Nine patients developed 12 periocular malignancies and 3 patients required eyelid surgery for facial malignancies outside the periocular zone. All 11 patients developed a squamous cell carcinoma (14 malignancies), and 1 patient (1 malignancy) also developed a periocular basal cell carcinoma. There was orbital invasion in 4 cases and paranasal and/or cavernous sinus invasion in 3 cases. Two patients underwent exenteration. Seven cases required reconstruction with a free flap or graft. Periocular sequelae included lower eyelid ectropion (6 malignancies), dry eye and/or exposure symptoms (8 malignancies), unilateral vision loss (3 malignancies), and facial nerve paresis (5 malignancies). Squamous cell carcinoma affecting the periocular region represents a risk of solid organ transplantation and may produce significant ocular morbidity, including the need for major eyelid reconstruction, globe loss, and disfiguring surgery. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Transport and interaction of cosmetic product material within the ocular surface: beauty and the beastly symptoms of toxic tears.

PubMed

Malik, Adeela; Claoué, Charles

2012-12-01

Eye cosmetics such as mascara, eye shadow and eyeliner are used extensively to highlight the eyes, and are normally applied external to the ocular surface. Adverse reactions of cosmetics within the ocular surface include mild discomfort, eyelid dermatitis, pre-corneal tear film instability, and keratitis. These are attributed mainly to the preservative (benzalkonium chloride (BAC)) constituent of cosmetic product material (CPM). Transport of CPM from an external environment to any location on the ocular surface, essentially precedes the adverse interactions occurring at the location, and the control of these transport modes is therefore of clinical relevance. The inter-transport of CPM across the TF occurs due to both diffusion and drift processes. Diffusion of neutral species is driven by concentration gradients, and the drift of cationic BAC is influenced by the inherent electric field; determined by the distribution of the various ions secreted into the aqueous layer, and the negative glycocalyx charge at the mucin layer. In the presence of mucin deficiency, the corneal epithelium is exposed to invasion by both incident BAC and lipophilic species. The transport of cationic BAC across the TF may be controlled by regulating the secretion of various electrolytes at the lacrimal gland. This is of clinical significance in reducing corneal epithelial adverse effects. However, the risks of adverse effects at the corneal surface due to invasion by the lipophilic species remain. Patients with mucin deficiency, and especially those on eye ointment/drops medication, should be discouraged from using cosmetics in a way likely to contaminate the TF. Copyright © 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Case control study of dry eye and related ocular surface abnormalities in Ibadan, Nigeria.

PubMed

Bekibele, C O; Baiyeroju, A M; Ajaiyeoba, A; Akang, E E U; Ajayi, B G K

2010-02-01

Tear instability is associated with symptoms of ocular discomfort and irritation. Many patients with dry eyes remain untreated due to improper diagnoses. To identify symptoms and surface abnormalities associated with dry eyes. One hundred and fifty-six eyes of 78 subjects attending the Eye Clinic of the University College Hospital Ibadan were screened for dry eyes/tear instability using rose Bengal stain (graded 0-9), tear break-up time (TBUT), Schirmer's 1 tests, tear meniscus height and a standardised symptoms questionnaire. Grades 4-9 rose Bengal staining were considered as positive dry eye and were compared with grades 0-3 staining eyes as negative controls. Mean tear meniscus height, Schirmer's test and TBUT were lower among cases than their corresponding control eyes. The difference between the mean Schirmer's test values of cases and their controls were statistically significant (P = 0.00 for right eyes and P = 0.002 for left eyes). Rose Bengal grades were inversely correlated with the mean Schirmer's values (Pearson correlation -0.429, P = 0.05 for right eyes and -0.335, P = 0.03 for left eyes) and TBUT (Pearson correlation -0.316, P = 0.05 for right eyes and -0.212, P = 0.06 for left eyes). About 95.8% of the cases were symptomatic, as opposed to 70.4% of the controls (P = 0.01, Fisher's exact test) and 95.8% of dry right eyes compared to 61.1% of their controls had ocular surface abnormalities (P = 0.001), while 89.5% of dry left eyes compared to 62.7% of controls had surface abnormalities (P = 0.07). A close relationship exists between ocular irritation symptoms, surface abnormalities and functional evidence of tear instability. Such patients should be treated empirically or screened for dry eyes.

The Effects of Increasing Ocular Surface Stimulation on Blinking and Sensation

PubMed Central

Wu, Ziwei; Begley, Carolyn G.; Situ, Ping; Simpson, Trefford

2014-01-01

Purpose. The purpose of this study was to determine how increasing ocular surface stimulation affected blinking and sensation, while controlling task concentration. Methods. Ten healthy subjects concentrated on a task while a custom pneumatic device generated air flow toward the central cornea. Six flow rates (FRs) were randomly presented three times each and subjects used visual analog scales to record their sensory responses. The interblink interval (IBI) and the FR were recorded simultaneously and the IBI, sensory response, and corresponding FR were determined for each trial. The FR associated with a statistically significant decrease in IBI, the blink increase threshold (BIT), was calculated for each subject. Results. Both the mean and SD of IBI were decreased with increasing stimulation, from 5.69 ± 3.96 seconds at baseline to 1.02 ± 0.37 seconds at maximum stimulation. The average BIT was 129 ± 20 mL/min flow rate with an IBI of 2.33 ± 1.10 seconds (permutation test, P < 0.001). After log transformation, there was a significant linear function between increasing FR and decreasing IBI within each subject (Pearson's r ≤ −0.859, P < 0.05). The IBI was highly correlated with wateriness, discomfort, and cooling ratings (Pearson's r ≤ −0.606, P < 0.001). Conclusions. There was a dose-response–like relationship between increased surface stimulation and blinking in healthy subjects, presumably for protection of the ocular surface. The blink response was highly correlated with ocular surface sensation, which is not surprising given their common origins. The BIT, a novel metric, may provide an additional end point for studies on dry eye or other conditions. PMID:24557346

Effects of poly(2-hydroxyethyl methacrylate) and poly(vinyl-pyrrolidone) hydrogel implants on myopic and normal chick sclera

PubMed Central

Su, James; Iomdina, Elena; Tarutta, Elena; Ward, Brian; Song, Jie; Wildsoet, Christine F.

2008-01-01

There has been generally little attention paid to the utilization of biomaterials as an anti-myopia treatment. The purpose of this study was to investigate whether polymeric hydrogels, either implanted or injected adjacent to the outer scleral surface, slow ocular elongation. White Leghorn (gallus gallus domesticus) chicks were used at 2 weeks of age. Chicks had either (1) strip of poly(2-hydroxyethyl methacrylate) (pHEMA) implanted monocularly against the outer sclera at the posterior pole, or (2) an in situ polymerizing gel [main ingredient: poly(vinyl-pyrrolidone) (PVP)] injected monocularly at the same location. Some of the eyes injected with the polymer were fitted with a diffuser or a −10D lens. In each experiment, ocular lengths were measured at regular intervals by high frequency A-scan ultrasonography, and chicks were sacrificed for histology at staged intervals. No in vivo signs of either orbital or ocular inflammation were observed. The pHEMA implant significantly increased scleral thickness by the third week, and the implant became encapsulated with fibrous tissue. The PVP-injected eyes left otherwise untreated, showed a significant increase in scleral thickness, due to increased chondrocyte proliferation and extracellular matrix deposition. However, there was no effect of the PVP injection on ocular elongation. In eyes wearing optical devices, there was no effect on either scleral thickness or ocular elongation. These results represent “proof of principle” that scleral growth can be manipulated without adverse inflammatory responses. However, since neither approach slowed ocular elongation, additional factors must influence scleral surface area expansion in the avian eye. PMID:19109950

A Novel Combination Therapy for Patients With Dry Eye Disease: A Pilot Study.

PubMed

Smith, Will; McMahon, David; Nymark, Maria

2018-05-01

Context • Approximately 25% of the US population suffers from dry eyes or some abnormality of the exposed ocular surface. Investigation of effective modalities for their management is needed. Objective • The study intended to examine the efficacy of a proprietary, daily, Dry Eye Protocol consisting of daily use of a moist, heated, ocular compress and intake of an omega-3 dietary supplement in treatment of ocular surface disease. Design • The research team designed a 4-wk, clinically based, open-label, multicenter cohort study. Setting • The study took place at 6 private eye care practices throughout the United States: Beverly Hills, CA, USA; San Diego, CA, USA; Sunnyvale, CA, USA; Park City, UT, USA; Tarpon Spring, FL, USA; and Kennewick, WA, USA. Participants • Participants were adults between 18 and 75 y of age who had established ocular surface disease based on clinical findings and the results of testing using the ocular surface disease index (OSDI). Intervention • For period of 30 d, participants used a combined daily protocol that included (1) application of a moist, heated, eye compress and (2) a nutritional therapy via an omega-3 supplement in an oral triglyceride form. Outcome Measures • Measures included the OSDI and a test of tear break-up time (TBUT). Results • Of the original 35 participants, 33 completed the 4-wk protocol. The participants using the proprietary Dry Eye Protocol showed significant improvements from baseline, demonstrated by a 49% decrease in OSDI scores (P = .0015); and 46% of participants reported becoming asymptomatic of dry eye symptoms. A significant improvement was also observed in TBUT, increasing from 3.0 to 5.4 s. Conclusions • Daily use of the proprietary Dry Eye Protocol that included a high dosage of triglyceride omega-3 and use of a moist, heated, compress daily showed significant improvement for participants in OSDI and TBUT and should be considered to be a first-line therapy for patients with dry eye disease.

Antimicrobial role of human meibomian lipids at the ocular surface.

PubMed

Mudgil, Poonam

2014-10-14

Human meibomian lipids form the outermost lipid layer of the tear film and serve many important functions to maintain its integrity. Although not investigated earlier, these lipids may have antimicrobial properties that help in strengthening the innate host defense of tears at the ocular surface. The aim of this study was to investigate the antimicrobial role of human meibomian lipids. Ocular pathogenic bacteria, Staphylococcus aureus 31, Pseudomonas aeruginosa 19, Pseudomonas aeruginosa 20, and Serratia marcescens 35, were grown in the presence and absence of human meibomian lipids in an artificial tear solution at the physiological temperature. Viable counts were obtained to note the number of bacteria surviving the treatment with meibomian lipids. Bacterial cells were imaged using scanning electron microscopy to observe the damages caused by meibomian lipids. Viable count results showed that in the presence of meibomian lipids, growth of all bacteria was considerably lower. Scanning electron microscopy showed that meibomian lipids caused extensive cellular damage to bacteria as manifested in smaller size, loss of aggregation, abnormal phenotype, cellular distortion, damaged cell wall, and cell lysis. This is the first-ever report of the antimicrobial role of human meibomian lipids. These lipids possess antimicrobial properties against both Gram-positive and Gram-negative bacteria and are involved in the innate host defense of tears in protecting the ocular surface against microbial pathogens. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

PRGF exerts more potent proliferative and anti-inflammatory effects than autologous serum on a cell culture inflammatory model.

PubMed

Anitua, E; Muruzabal, F; de la Fuente, M; Riestra, A; Merayo-Lloves, J; Orive, G

2016-10-01

Ocular graft versus host disease (oGVHD) is part of a systemic inflammatory disease that usually affects ocular surface tissues manifesting as a dry eye syndrome. Current treatments provide unsatisfactory results. Blood-derived products, like plasma rich in growth factors (PRGF) emerge as a potential therapy for this disease. The purpose of this study was to evaluate the tissue regeneration and anti-inflammatory capability of PRGF, an autologous platelet enriched plasma eye-drop, compared to autologous serum (AS) obtained from oGVHD patients on ocular surface cells cultured in a pro-inflammatory environment. PRGF and AS were obtained from four GVHD patients. Cell proliferation and inflammation markers, intercellular adhesion molecule-1 (ICAM-1) and cyclooxygenase-2 (COX-2), were measured in corneal and conjunctival fibroblastic cells cultured under pro-inflammatory conditions and after treatment with PRGF or AS eye drops. Moreover, cell proliferation increased after treatment with PRGF and AS, though this enhancement in the case of keratocytes was significantly higher with PRGF. PRGF eye drops showed a significant reduction of both inflammatory markers with respect to the initial inflammatory situation and to the AS treatment. Our results concluded that PRGF exerts more potent regenerative and anti-inflammatory effects than autologous serum on ocular surface fibroblasts treated with pro-inflammatory IL-1β and TNFα. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mucosal tolerance disruption favors disease progression in an extraorbital lacrimal gland excision model of murine dry eye.

PubMed

Guzmán, Mauricio; Keitelman, Irene; Sabbione, Florencia; Trevani, Analía S; Giordano, Mirta N; Galletti, Jeremías G

2016-10-01

Dry eye is a highly prevalent immune disorder characterized by a dysfunctional tear film and a Th1/Th17 T cell response at the ocular surface. The specificity of these pathogenic effector T cells remains to be determined, but auto-reactivity is considered likely. However, we have previously shown that ocular mucosal tolerance to an exogenous antigen is disrupted in a scopolamine-induced murine dry eye model and that it is actually responsible for disease progression. Here we report comparable findings in an entirely different murine model of dry eye that involves resection of the extraorbital lacrimal glands but no systemic muscarinic receptor blockade. Upon ocular instillation of ovalbumin, a delayed breakdown in mucosal tolerance to this antigen was observed in excised but not in sham-operated mice, which was mediated by interferon γ- and interleukin 17-producing antigen-specific T cells. Consistently, antigen-specific regulatory T cells were detectable in sham-operated but not in excised mice. As for other models of ocular surface disorders, epithelial activation of the NF-κB pathway by desiccating stress was determinant in the mucosal immune outcome. Underscoring the role of mucosal tolerance disruption in dry eye pathogenesis, its prevention by a topical NF-κB inhibitor led to reduced corneal damage in excised mice. Altogether these results show that surgically originated desiccating stress also initiates an abnormal Th1/Th17 T cell response to harmless exogenous antigens that reach the ocular surface. This event might actually contribute to corneal damage and challenges the conception of dry eye as a strictly autoimmune disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of bilastine upon the ocular symptoms of allergic rhinoconjunctivitis.

PubMed

Bartra, J; Mullol, J; Montoro, J; Jáuregui, I; del Cuvillos, A; Dávila, I; Ferrer, M; Sastre, J; Valero, A

2011-01-01

Ocular symptoms often accompany allergic rhinitis and can be as or even more bothersome for the patient than the actual nasal symptoms. Ocular manifestations of allergic rhinoconjunctivitis may result from both direct allergen-mediated mast cell stimulation on the surface of the eye and naso-ocular reflexes--histamine being one of the mediators of symptoms onset. An H1 antihistamine would be the first line treatment for allergic conjunctivitis. Since allergic conjunctivitis is always (or almost always) accompanied by nasal symptoms, a second-generation H1 antihistamine administered via oral route is the drug of choice for jointly managing both the nasal and the ocular symptoms--minimizing the impact of the effects inherent to first-generation H, antihistamine, including particularly drowsiness. Bilastine is a new H1 antihistamine with an excellent safety profile, developed for the treatment of allergic rhinoconjunctivitis and urticaria, with potency similar to that of cetirizine and desloratadine, and superior to that of fexofenadine. This new drug has been shown to be effective in controlling the ocular symptoms of allergic rhinoconjunctivitis.

Design and elaboration of freeze-dried PLGA nanoparticles for the transcorneal permeation of carprofen: Ocular anti-inflammatory applications.

PubMed

Parra, Alexander; Mallandrich, Mireia; Clares, Beatriz; Egea, María A; Espina, Marta; García, María L; Calpena, Ana C

2015-12-01

This work aimed the design and development of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) for the ocular delivery of Carprofen (CP) by a central rotatable composite design 2(3)+ star. NPs showed adequate size for ocular administration (189.50 ± 1.67 nm), low polydispersity (0.01 ± 0.01), negative charge surface (-22.80 ± 0.66 mV) and optimal entrapment efficiency (74.70 ± 0.95%). Physicochemical analysis confirmed that CP was dispersed inside the NPs. The drug release followed a first order kinetic model providing greater sustained CP release after lyophilization. Ex vivo permeation analysis through isolated rabbit cornea revealed that a sufficient amount of CP was retained in the tissue avoiding excessive permeation and thus, potential systemic levels. Ex vivo ocular tolerance results showed no signs of ocular irritancy, which was also confirmed by in vivo Draize test. In vivo ocular anti-inflammatory efficacy test confirmed an optimal efficacy of NPs and its potential application in eye surgery. Copyright © 2015 Elsevier B.V. All rights reserved.

Incomplete response to artificial tears is associated with features of neuropathic ocular pain.

PubMed

Galor, Anat; Batawi, Hatim; Felix, Elizabeth R; Margolis, Todd P; Sarantopoulos, Konstantinos D; Martin, Eden R; Levitt, Roy C

2016-06-01

Artificial tears are first-line therapy for patients with dry eye symptoms. It is not known, however, which patient factors associate with a positive response to therapy. The purpose of this study was to evaluate whether certain ocular and systemic findings are associated with a differential subjective response to artificial tears. Cross-sectional study of 118 individuals reporting artificial tears use (hypromellose 0.4%) to treat dry eye-associated ocular pain. An evaluation was performed to assess dry eye symptoms (via the dry eye questionnaire 5 and ocular surface disease index), ocular and systemic (non-ocular) pain complaints and ocular signs (tear osmolarity, tear breakup time, corneal staining, Schirmer testing with anaesthesia, and eyelid and meibomian gland assessment). The main outcome measures were factors associated with differential subjective response to artificial tears. By self-report, 23 patients reported no improvement, 73 partial improvement and 22 complete improvement in ocular pain with artificial tears. Patients who reported no or partial improvement in pain with artificial tears reported higher levels of hot-burning ocular pain and sensitivity to wind compared with those with complete improvement. Patients were also asked to rate the intensity of systemic pain elsewhere in the body (other than the eye). Patients who reported no or incomplete improvement with artificial tears had higher systemic pain scores compared with those with complete improvement. Both ocular and systemic (non-ocular) pain complaints are associated with a differential subjective response to artificial tears. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Vision-Related Quality of Life in Patients with Ocular Graft-versus-Host Disease.

PubMed

Saboo, Ujwala S; Amparo, Francisco; Abud, Tulio B; Schaumberg, Debra A; Dana, Reza

2015-08-01

To assess the vision-related quality of life (QOL) in a cohort of patients with ocular graft-versus-host disease (GVHD). Prospective study. Eighty-four patients diagnosed with chronic ocular GVHD. We assessed the vision-related QOL with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). The symptoms of ocular GVHD were assessed using the Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE) questionnaires. We assessed vision-related QOL with the NEI-VFQ-25 and compared the scores obtained from patients with ocular GVHD with those from a healthy population. In the ocular GVHD population, we also evaluated the associations between the NEI-VFQ-25 and the dry eye symptoms measured by the OSDI and SANDE questionnaires, age, duration of disease, best-corrected visual acuity (BCVA), corneal fluorescein staining (CFS), tear break-up time, and Schirmer test. The mean composite NEI-VFQ-25 score in patients with ocular GVHD was 76.5±17. Compared with healthy subjects, patients with ocular GVHD reported reduced scores on all NEI-VFQ-25 subscales (each P < 0.001) with the exception of color vision (P = 0.11). The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = -0.81, P < 0.001), SANDE (R = -0.56, P < 0.001), CFS (R = -0.36, P = 0.001), and BCVA (R = -0.30, P = 0.004). Patients with ocular GVHD experience measurable impairment of vision-related QOL. This study highlights the impact of ocular GVHD on the vision-related QOL, and thus the importance of comprehensive diagnosis and treatment of this condition. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Vision-Related Quality of Life in Patients with Ocular Graft-versus-host Disease

PubMed Central

Saboo, Ujwala S; Amparo, Francisco; Abud, Tulio B; Schaumberg, Debra A; Dana, Reza

2015-01-01

Objective To assess the vision-related quality of life in a cohort of patients with ocular graft-versus-host disease (GVHD). Design Prospective study. Participants Eighty-four patients diagnosed with chronic ocular GVHD Methods We assessed the vision-related quality of life with the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). The symptoms of ocular GVHD were assessed using the Ocular Surface Disease Index (OSDI) and Symptom Assessment in Dry Eye (SANDE) questionnaires. Main outcome measures We assessed vision-related quality of life with NEI-VFQ-25 and compared the scores obtained from patients with ocular GVHD to those from a healthy population. In the ocular GVHD population, we also evaluated the associations between the NEI-VFQ-25 and dry eye symptoms measured by OSDI and SANDE questionnaires, age, duration of disease, best-corrected visual acuity, corneal fluorescein staining, tear break-up time, and Schirmer test. Results The mean composite NEI-VFQ-25 score in patients with ocular GVHD was 76.5 ± 17. Compared to healthy subjects, ocular GVHD patients reported reduced scores on all NEI-VFQ-25 subscales (each P < 0.001) with exception of color vision (P = 0.11). The NEI-VFQ-25 composite scores significantly correlated with OSDI (R = −0.81, P < 0.001), SANDE (R = −0.56, P < 0.001), corneal fluorescein staining (R = −0.36, P = 0.001) and best-corrected visual acuity (R = −0.30, P = 0.004). Conclusion Patients with ocular GVHD experience measurable impairment of vision-related quality of life. This study highlights the impact of ocular GVHD on the vision-related quality of life, and hence the importance of comprehensive diagnosis and treatment of this condition. PMID:26001816

Corneal Sensitivity in Tear Dysfunction and its Correlation with Clinical Parameters and Blink Rate

PubMed Central

Rahman, Effie Z.; Lam, Peter K.; Chu, Chia-Kai; Moore, Quianta; Pflugfelder, Stephen C.

2015-01-01

Purpose To compare corneal sensitivity in tear dysfunction due to a variety of causes using contact and non-contact esthesiometers and to evaluate correlations between corneal sensitivity, blink rate and clinical parameters. Design Comparative observational case series. Methods Ten normal and 33 subjects with tear dysfunction [meibomian gland disease (n = 11), aqueous tear deficiency (n = 10) - without (n = 7) and with (n = 3) Sjögren syndrome (SS) and conjunctivochalasis (n = 12)] were evaluated. Corneal sensitivity was measured with Cochet-Bonnet and air jet esthesiometers and blink rate by electromyelography. Eye irritation symptoms, tear meniscus height, tear break-up time (TBUT), and corneal and conjunctival dye staining were measured. Between group means were compared and correlations calculated. Results Compared with control (Cochet-Bonnet 5.45 mm, air esthesiometer 3.62 mg), mean sensory thresholds were significantly higher in aqueous tear deficiency using either Cochet-Bonnet (3.6 mm; P = 0.003) or air (11.7 mg; P = 0.046) esthesiometers, but were not significantly different in the other groups. Reduced corneal sensitivity significantly correlated with more rapid TBUT and blink rate, and greater irritation and ocular surface dye staining with one or both esthesiometers. Mean blink rates were significantly higher in both aqueous tear deficiency and conjunctivochalasis compared with control. Among all subjects, blink rate positively correlated with ocular surface staining and irritation and inversely correlated with TBUT. Conclusion Amongst conditions causing tear dysfunction, reduced corneal sensitivity is associated with greater irritation, tear instability, ocular surface disease and blink rate. Rapid blinking is associated with worse ocular surface disease and tear stability. PMID:26255576

[Eye-associated lymphoid tissue (EALT) is continuously spread throughout the ocular surface from the lacrimal gland to the lacrimal drainage system].

PubMed

Knop, E; Knop, N

2003-11-01

Components of the mucosal immune system (MALT) have been identified in the conjunctiva (as CALT) and the lacrimal drainage system (as LDALT). Their structural and functional relation with the established immune protection by the lacrimal gland is unclear. Macroscopically normal and complete tissues of the conjunctiva, lacrimal drainage system and lacrimal gland from human body donors were investigated by analysis of translucent whole mounts, and using histology, immunohistology as well as scanning and transmission electron microscopy. A typical diffuse lymphoid tissue, composed of effector cells of the immune system (T-lymphocytes and IgA producing plasma cells) under an epithelium that contains the IgA transporter SC, is not isolated in the conjunctiva and lacrimal drainage system. It is anatomically continuous from the lacrimal gland along its excretory ducts into the conjunctiva and from there via the lacrimal canaliculi into the lacrimal drainage system. Lymphoid follicles occur in a majority (about 60%) and with bilateral symmetry. The topography of CALT corresponds to the position of the cornea in the closed eye. These results show that the MALT of the lacrimal gland, conjunctiva and lacrimal drainage system constitute an anatomical and functional unit for immune protection of the ocular surface. Therefore it should be integrated as an "eye-associated lymphoid tissue" (EALT) into the MALT system of the body. EALT can detect ocular surface antigens by the lymphoid follicles and can supply other organs and the ocular surface including the lacrimal gland with specific effector cells via the regulated recirculation of lymphoid cells.

Efficacy of punctal occlusion in management of dry eyes after laser in situ keratomileusis for myopia.

PubMed

Alfawaz, Abdullah M; Algehedan, Saeed; Jastaneiah, Sabah S; Al-Mansouri, Samir; Mousa, Ahmed; Al-Assiri, Abdullah

2014-03-01

To evaluate the effect of punctal plug use in preventing dry eye after laser in situ keratomileusis (LASIK). A randomized clinical trial at a tertiary eye care center, Riyadh, Saudi Arabia. Participants underwent LASIK for myopia in both eyes and a lower punctal occlusion in one eye only while the other eye served as control. Both eyes received the same postoperative medications except for lubricant duration (subject eye: four times per day for one week; control eye: four times per day for 6 months). Participants were evaluated at 1 week, 2, and 6 months after surgery for signs and symptoms of dry eye. The main outcome measures were visual acuity; ocular surface parameters; and Ocular Surface Disease Index questionnaire. Seventy-eight eyes of 39 patients were included in this study. The Ocular Surface Disease Index scores of eyes with punctal plugs were better at all follow-up visits, and the differences between both eyes were statistically significant (1 week, p < 0.0001; 2 months, p < 0.0001; 6 months, p = 0.008). At the final follow-up visit, the percentage of normal eyes was higher in eyes with punctal plugs for all ocular surface parameters (Schirmer 1 test, 94.9%; tear breakup time, 77.8%; punctate epithelial keratitis score, 71.8%) compared to eyes without occlusion (Schirmer 1 test, 92.3%; tear breakup time, 58.3%; punctate epithelial keratitis score, 53.8%); however, such differences were not statistically significant. Punctal plug insertion after LASIK surgeries may minimize the need for frequent lubricant application and hence improve patient satisfaction.

Tear cytokine profile as a noninvasive biomarker of inflammation for ocular surface diseases: standard operating procedures.

PubMed

Wei, Yi; Gadaria-Rathod, Neha; Epstein, Seth; Asbell, Penny

2013-12-23

To provide standard operating procedures (SOPs) for measuring tear inflammatory cytokine concentrations and to validate the resulting profile as a minimally invasive objective metric and biomarker of ocular surface inflammation for use in multicenter clinical trials on dry eye disease (DED). Standard operating procedures were established and then validated with cytokine standards, quality controls, and masked tear samples collected from local and distant clinical sites. The concentrations of the inflammatory cytokines in tears were quantified using a high-sensitivity human cytokine multiplex kit. A panel of inflammatory cytokines was initially investigated, from which four key inflammatory cytokines (IL-1β, IL-6, INF-γ, and TNF-α) were chosen. Results with cytokine standards statistically satisfied the manufacturer's quality control criteria. Results with pooled tear samples were highly reproducible and reliable with tear volumes ranging from 4 to 10 μL. Incorporation of the SOPs into clinical trials was subsequently validated. Tear samples were collected at a distant clinical site, stored, and shipped to our Biomarker Laboratory, where a masked analysis of the four tear cytokines was successfully performed. Tear samples were also collected from a feasibility study on DED. Inflammatory cytokine concentrations were decreased in tears of subjects who received anti-inflammatory treatment. Standard operating procedures for human tear cytokine assessment suitable for multicenter clinical trials were established. Tear cytokine profiling using these SOPs may provide objective metrics useful for diagnosing, classifying, and analyzing treatment efficacy in inflammatory conditions of the ocular surface, which may further elucidate the mechanisms involved in the pathogenesis of ocular surface disease.

TFOS DEWS II pain and sensation report

PubMed Central

Belmonte, Carlos; Nichols, Jason J.; Cox, Stephanie M.; Brock, James A.; Begley, Carolyn G.; Bereiter, David A.; Dartt, Darlene A.; Galor, Anat; Hamrah, Pedram; Ivanusic, Jason J.; Jacobs, Deborah S.; McNamara, Nancy A.; Rosenblatt, Mark I.; Stapleton, Fiona; Wolffsohn, James S.

2017-01-01

Pain associated to mechanical and chemical irritation of the eye surface is mediated by trigeminal ganglia mechano- and polymodal nociceptor neurons while cold thermoreceptors detect wetness and reflexly maintain basal tear production and blinking rate. These neurons project into two regions of the trigeminal brain stem nuclear complex: ViVc, activated by changes in the moisture of the ocular surface and VcC1, mediating sensory-discriminative aspects of ocular pain and reflex blinking. ViVc ocular neurons project to brain regions that control lacrimation and spontaneous blinking and to the sensory thalamus. Secretion of the main lacrimal gland is regulated dominantly by autonomic parasympathetic nerves, reflexly activated by eye surface sensory nerves. These also evoke goblet cell secretion through unidentified efferent fibers. Neural pathways involved in the regulation of Meibonian gland secretion or mucins release have not been identified. In dry eye disease, reduced tear secretion leads to inflammation and peripheral nerve damage. Inflammation causes sensitization of polymodal and mechano-nociceptor nerve endings and an abnormal increase in cold thermoreceptor activity, altogether evoking dryness sensations and pain. Long-term inflammation and nerve injury alter gene expression of ion channels and receptors at terminals and cell bodies of trigeminal ganglion and brainstem neurons, changing their excitability, connectivity and impulse firing. Perpetuation of molecular, structural and functional disturbances in ocular sensory pathways ultimately leads to dysestesias and neuropathic pain referred to the eye surface. Pain can be assessed with a variety of questionaires while the status of corneal nerves is evaluated with esthesiometry and with in vivo confocal microscopy. PMID:28736339

[Research progress of conscious pain and neurosensory abnormalities in dry eye disease].

PubMed

Lin, X; Liu, Z L; Wu, J L; Liu, Z G

2018-02-11

Dry eye is one of the most common ocular problems in ophthalmology clinic. With the change of social environment and people's life style, the prevalence of dry eye disease is increasing. Currently, the diagnosis criteria for dry eye is controversial, diagnosis of dry eye mainly rely on the comprehensive assessment of symptoms and the presence of associated ocular surface signs. However, previous studies have shown a poor correlation between dry eye symptoms and objective clinical signs in patients. Recent studies have found that neuropathic pain plays an important role in the occurrence of discordance between symptoms and signs in dry eye disease. The purpose of this paper is to present the conception of pain, the distribution and function of sensory nerves in ocular surface, the prevalence and mechanism of neuropathic pain and analgesic treatment in dry eye disease. (Chin J Ophthalmol, 2018, 54: 144-148) .

Correlation between acute conjunctivitis and Asian dust on ocular surfaces.

PubMed

Ko, Ryota; Hayashi, Masahiko; Hayashi, Hideyuki; Hayashi, Kazue; Kato, Hitoshi; Kurata, Yoshinori; Fuchino, Yuki; Nakamichi, Toshifumi; Migita, Hironori; Yano, Hiroko; Sakata, Tetsuya; Uchio, Eiichi

2016-01-01

The aim of this study was to determine the presence of Asian dust particles (ADP) in patients suffering from conjunctivitis and its correlation with clinical scores for conjunctivitis. Forty-five patients from the Fukuoka area who were newly diagnosed acute conjunctivitis were selected. The degrees of inflammatory reaction, itchy sensation, hyperemia, eye discharge, and foreign body sensation were clinically recorded and scored. Eyes were washed with physiological solution. Solid particles collected from the washing solution were observed using a scanning electron microscope. Of the 45 samples, 44 were positive for the elements silicon (Si) and aluminum (Al), which are components of ambient Asian dust. Higher conjunctivitis scores were found in the subgroup in which the Asian dust/whole particle ratio was greater than average. This is the first apparent report on the correlation between amount of ADP exposure at the ocular surface and severity of ocular symptoms.

Effects of lodoxamide (LOD), disodium cromoglycate (DSCG) and N-acetyl-aspartyl-glutamate sodium salt (NAAGA) on ocular active anaphylaxis.

PubMed

Goldschmidt, P; Luyckx, J

1996-04-01

LOD, DSCG and NAAGA eye-drops were evaluated on experimentally-induced ocular active anaphylaxis in guinea pigs. Twelve animals per group were sensitized with egg albumin i.p. and challenged on the surface of the eye 14 days later. Two days before challenge, animals were treated with LOD, DSCG or NAAGA 4 times a day. Permeability indexes were calculated after intracardiac injection of Evans Blue. No effect on ocular active anaphylaxis was found with LOD nor with DSCG. NAAGA was able to significantly reduce blood-eye permeability indexes.

Surface modification of model hydrogel contact lenses with hyaluronic acid via thiol-ene "click" chemistry for enhancing surface characteristics.

PubMed

Korogiannaki, Myrto; Zhang, Jianfeng; Sheardown, Heather

2017-10-01

Discontinuation of contact lens wear as a result of ocular dryness and discomfort is extremely common; as many as 26% of contact lens wearers discontinue use within the first year. While patients are generally satisfied with conventional hydrogel lenses, improving on-eye comfort continues to remain a goal. Surface modification with a biomimetic, ocular friendly hydrophilic layer of a wetting agent is hypothesized to improve the interfacial interactions of the contact lens with the ocular surface. In this work, the synthesis and characterization of poly(2-hydroxyethyl methacrylate) surfaces grafted with a hydrophilic layer of hyaluronic acid are described. The immobilization reaction involved the covalent attachment of thiolated hyaluronic acid (20 kDa) on acrylated poly(2-hydroxyethyl methacrylate) via nucleophile-initiated Michael addition thiol-ene "click" chemistry. The surface chemistry of the modified surfaces was analyzed by Fourier transform infrared spectroscopy-attenuated total reflectance and X-ray photoelectron spectroscopy. The appearance of N (1s) and S (2p) peaks on the low resolution X-ray photoelectron spectroscopy spectra confirmed successful immobilization of hyaluronic acid. Grafting hyaluronic acid to the poly(2-hydroxyethyl methacrylate) surfaces decreased the contact angle, the dehydration rate, and the amount of nonspecific sorption of lysozyme and albumin in comparison to pristine hydrogel materials, suggesting the development of more wettable surfaces with improved water-retentive and antifouling properties, while maintaining optical transparency (>92%). In vitro testing also showed excellent viability of human corneal epithelial cells with the hyaluronic acid-grafted poly(2-hydroxyethyl methacrylate) surfaces. Hence, surface modification with hyaluronic acid via thiol-ene "click" chemistry could be useful in improving contact lens surface properties, potentially alleviating symptoms of contact lens related dryness and discomfort during wear.

Neural Regulation of Lacrimal Gland Secretory Processes: Relevance in Dry Eye Diseases

PubMed Central

Dartt, Darlene A.

2013-01-01

The lacrimal gland is the major contributor to the aqueous layer of the tear film which consists of water, electrolytes and proteins. The amount and composition of this layer is critical for the health, maintenance, and protection of the cells of the cornea and conjunctiva (the ocular surface). Small changes in the concentration of tear electrolytes have been correlated with dry eye syndrome. While the mechanisms of secretion of water, electrolytes and proteins from the lacrimal gland differ, all three are under tight neural control. This allows for a rapid response to meet the needs of the cells of the ocular surface in response to environmental conditions. The neural response consists of the activation of the afferent sensory nerves in the cornea and conjunctiva to stimulate efferent parasympathetic and sympathetic nerves that innervate the lacrimal gland. Neurotransmitters are released from the stimulated parasympathetic and sympathetic nerves that cause secretion of water, electrolytes, and proteins from the lacrimal gland and onto the ocular surface. This review focuses on the neural regulation of lacrimal gland secretion under normal and dry eye conditions. PMID:19376264

[Hyperosmolarity: Intracellular effects and implication in dry eye disease].

PubMed

Warcoin, E; Clouzeau, C; Brignole-Baudouin, F; Baudouin, C

2016-09-01

Dry eye disease is a multifactorial disease affecting the lacrimal functional unit and which has a significant impact on the quality of life of patients. This pathology works as a vicious circle at the ocular surface in which hyperosmolarity of the tear film plays a key role. This review intends to describe the different reported intracellular effects induced by hyperosmolarity in cells: alteration of cytoskeleton, cell cycle slowdown, adaptation mechanisms triggered as restoration of cell volume and accumulation of compatible osmolytes, the crucial role of the osmoprotectant factor Nuclear Factor of the Activated T cells-5 (NFAT5), apoptosis, as well as oxidative stress and inflammatory responses caused by this particular condition. Reported effects of hyperosmolarity in the experimental studies specific of dry eye disease concerning ocular surface cells will be described in parallel. Indeed, these data allow to understand a part of the pathophysiology of the disease, and specially the links between tear hyperosmolarity and inflammation of the ocular surface, the second key of the pathology phenomenon. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

An assessment of the pattern of spontaneous eyeblink activity under the influence of topical ocular anaesthesia.

PubMed

Naase, Taher; Doughty, Michael J; Button, Norman F

2005-04-01

To determine whether there is a change in the pattern of human eyeblink events under topical ocular anaesthesia. Forty male subjects, aged between 19 and 52 years and with no significant ocular surface disease, were recruited. Their spontaneous eyeblink activity, in primary eye gaze position and in silence, was recorded for 5-min periods, before and after instillation of benoxinate 0.4% eyedrops. The surface anaesthesia was confirmed by aesthesiometry. The spontaneous eyeblink rate (SEBR) decreased from 9.1+/-4.0 blinks/min to an average of 5.7+/-3.3 blinks/min, with 37 subjects showing a decreased eyeblink rate under anaesthesia. Three blink patterns were observed before anaesthesia (symmetrical, J-type and I-type) and these were essentially unchanged under anaesthesia. These studies confirm that the SEBR is usually reduced under surface anaesthesia (so is sensitive to exogenous control) but the pattern of the eyeblink activity is unchanged (so is less sensitive to exogenous control). The removal of exogenous stimuli by anaesthesia does not shift the eyeblink pattern to a single type, so indicates endogenous control.

Real-time dose calculation and visualization for the proton therapy of ocular tumours

NASA Astrophysics Data System (ADS)

Pfeiffer, Karsten; Bendl, Rolf

2001-03-01

A new real-time dose calculation and visualization was developed as part of the new 3D treatment planning tool OCTOPUS for proton therapy of ocular tumours within a national research project together with the Hahn-Meitner Institut Berlin. The implementation resolves the common separation between parameter definition, dose calculation and evaluation and allows a direct examination of the expected dose distribution while adjusting the treatment parameters. The new tool allows the therapist to move the desired dose distribution under visual control in 3D to the appropriate place. The visualization of the resulting dose distribution as a 3D surface model, on any 2D slice or on the surface of specified ocular structures is done automatically when adapting parameters during the planning process. In addition, approximate dose volume histograms may be calculated with little extra time. The dose distribution is calculated and visualized in 200 ms with an accuracy of 6% for the 3D isodose surfaces and 8% for other objects. This paper discusses the advantages and limitations of this new approach.

Potential Role of Induced Pluripotent Stem Cells (IPSCs) for Cell-Based Therapy of the Ocular Surface

PubMed Central

Casaroli-Marano, Ricardo P.; Nieto-Nicolau, Núria; Martínez-Conesa, Eva M.; Edel, Michael; Álvarez-Palomo, Ana B.

2015-01-01

The integrity and normal function of the corneal epithelium are crucial for maintaining the cornea’s transparency and vision. The existence of a cell population with progenitor characteristics in the limbus maintains a dynamic of constant epithelial repair and renewal. Currently, cell-based therapies for bio replacement—cultured limbal epithelial transplantation (CLET) and cultured oral mucosal epithelial transplantation (COMET)—present very encouraging clinical results for treating limbal stem cell deficiency (LSCD) and restoring vision. Another emerging therapeutic approach consists of obtaining and implementing human progenitor cells of different origins in association with tissue engineering methods. The development of cell-based therapies using stem cells, such as human adult mesenchymal or induced pluripotent stem cells (IPSCs), represent a significant breakthrough in the treatment of certain eye diseases, offering a more rational, less invasive, and better physiological treatment option in regenerative medicine for the ocular surface. This review will focus on the main concepts of cell-based therapies for the ocular surface and the future use of IPSCs to treat LSCD. PMID:26239129

IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duprez, Frederic, E-mail: frederic.duprez@ugent.be; Madani, Indira; Morbee, Lieve

2012-05-01

Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages weremore » T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival. Avoidance of severe dry eye syndrome and radiation-induced blindness suggests IMRT as a standard treatment for sinonasal tumors.« less

Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye.

PubMed

Ramsay, Eva; Del Amo, Eva M; Toropainen, Elisa; Tengvall-Unadike, Unni; Ranta, Veli-Pekka; Urtti, Arto; Ruponen, Marika

2018-07-01

On the surface of the eye, both the cornea and conjunctiva are restricting ocular absorption of topically applied drugs, but barrier contributions of these two membranes have not been systemically compared. Herein, we studied permeability of 32 small molecular drug compounds across an isolated porcine cornea and built a quantitative structure-property relationship (QSPR) model for the permeability. Corneal drug permeability (data obtained for 25 drug molecules) showed a 52-fold range in permeability (0.09-4.70 × 10 -6  cm/s) and the most important molecular descriptors in predicting the permeability were hydrogen bond donor, polar surface area and halogen ratio. Corneal permeability values were compared to their conjunctival drug permeability values. Ocular drug bioavailability and systemic absorption via conjunctiva were predicted for this drug set with pharmacokinetic calculations. Drug bioavailability in the aqueous humour was simulated to be <5% and trans-conjunctival systemic absorption was 34-79% of the dose. Loss of drug across the conjunctiva to the blood circulation restricts significantly ocular drug bioavailability and, therefore, ocular absorption does not increase proportionally with the increasing corneal drug permeability. Copyright © 2018 Elsevier B.V. All rights reserved.

Correlations among ocular surface temperature difference value, the tear meniscus height, Schirmer's test and fluorescein tear film break up time.

PubMed

Su, Tai Yuan; Ho, Wei Ting; Lu, Chien Yi; Chang, Shu Wen; Chiang, Huihua Kenny

2015-04-01

To report the use of a thermographer for measuring ocular surface temperature, and to evaluate the correlation among the obtained temperature difference values (TDVs) and dry eye parameters (tear meniscus height (TMH); Schirmer's test results; fluorescent tear breakup time (FTBUT)). Forty-three participants (age 40.2±14.7 years; range 21-67 years) from Far Eastern Memorial Hospital, Taiwan were recruited for the study. The surface temperature was measured at the centre of the ocular surface for 4 s after blinking. TDV was defined as the change in corneal surface temperature relative to that of the preceding eye opening, where TDV01, TDV02, TDV03, and TDV04 represent the values obtained 1, 2, 3, and 4 s after blinking, respectively. Anterior segment optical coherence tomography (AS-OCT) was employed to measure the lower TMH. Schirmer's test with topical anaesthetic was conducted to measure the basal tear secretion. The FTBUT was recorded using a digital camera. TDV measurement exhibited high reliability (intraclass correlation coefficient=0.91). TDV03 exhibited the highest significance and strongest positive correlation with the TMH (r=0.52, p=0.0003) and Schirmer's test value (r=0.39, p=0.008), whereas the TDV03-FTBUT correlation was non-significant. Age correlated negatively and significantly with the TDV (r= -0.35, p=0.021), TMH (r= -0.33, p=0.031), and Schirmer's test value (r= -0.31, p=0.044). TDV03 remained significantly correlated with the TMH and Schirmer's test value after adjustment for age. The thermographer was effective in capturing temperature changes in the ocular surface. The temperature difference 3 s after blinking appears to be correlated with lower TMH and Schirmer test values. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Inflammation in dry eye.

PubMed

Stern, Michael E; Pflugfelder, Stephen C

2004-04-01

Dry eye is a condition of altered tear composition that results from a diseased or dysfunctional lacrimal functional unit. Evidence suggests that inflammation causes structural alterations and/or functional paralysis of the tear-secreting glands. Changes in tear composition resulting from lacrimal dysfunction, increased evaporation and/or poor clearance have pro-inflammatory effects on the ocular surface. This inflammation is responsible in part for the irritation symptoms, ocular surface epithelial disease, and altered corneal epithelial barrier function in dry eye. Anti-inflammatory therapies for dry eye target one or more of the inflammatory mediators/pathways that have been identified in dry eye.

Simulations of simple Bovine and Homo sapiens outer cortex ocular lens membrane models with a majority concentration of cholesterol.

PubMed

Adams, Mark; Wang, Eric; Zhuang, Xiaohong; Klauda, Jeffery B

2017-11-21

The lipid composition of bovine and human ocular lens membranes has been probed, and a variety of lipids have been found including phosphatidylcholine (PC), phosphatidylethanolamine (PE), sphingomyelin (SM), and cholesterol (CHOL) with cholesterol being present in particularly high concentrations. In this study, we use the all-atom CHARMM36 force field to simulate binary, ternary, and quaternary mixtures as models of the ocular lens. High concentration of cholesterol, in combination with different and varying diversity of phospholipids (PL) and sphingolipids (SL), affect the structure of the ocular lens lipid bilayer. The following analyses were done for each simulation: surface area per lipid, component surface area per lipid, deuterium order parameters (S CD ), electron density profiles (EDP), membrane thickness, hydrogen bonding, radial distribution functions, clustering, and sterol tilt angle distribution. The S CD show significant bilayer alignment and packing in cholesterol-rich bilayers. The EDP show the transition from liquid crystalline to liquid ordered with the addition of cholesterol. Hydrogen bonds in our systems show the tendency for intramolecular interactions between cholesterol and fully saturated lipid tails for less complex bilayers. But with an increased number of components in the bilayer, the acyl chain of the lipids becomes a less important characteristic, and the headgroup of the lipid becomes more significant. Overall, cholesterol is the driving force of membrane structure of the ocular lens membrane where interactions between cholesterol, PL, and SL determine structure and function of the biomembrane. The goal of this work is to develop a baseline for further study of more physiologically realistic ocular lens lipid membranes. This article is part of a Special Issue entitled: Emergence of Complex Behavior in Biomembranes edited by Marjorie Longo. Copyright © 2017 Elsevier B.V. All rights reserved.

Correlation of Superior Canal Dehiscence Surface Area With Vestibular Evoked Myogenic Potentials, Audiometric Thresholds, and Dizziness Handicap.

PubMed

Hunter, Jacob B; O'Connell, Brendan P; Wang, Jianing; Chakravorti, Srijata; Makowiec, Katie; Carlson, Matthew L; Dawant, Benoit; McCaslin, Devin L; Noble, Jack H; Wanna, George B

2016-09-01

To correlate objective measures of vestibular and audiometric function as well as subjective measures of dizziness handicap with the surface area of the superior canal dehiscence (SCD). Retrospective chart review and radiological analysis. Single tertiary academic referral center. Preoperative computed tomography imaging, patient survey, audiometric thresholds, and vestibular evoked myogenic potential (VEMP) testing in patients with confirmed SCD. Image analysis techniques were developed to measure the surface area of each SCD in computed tomography imaging. Preoperative ocular and cervical VEMPs, air and bone conduction thresholds, air-bone gap, dizziness handicap inventory scores, and surface area of the SCD. Fifty-three patients (mean age 52.7 yr) with 84 SCD were analyzed. The median surface area of dehiscence was 1.44 mm (0.068-8.23 mm). Ocular VEMP amplitudes (r = 0.61, p <0.0001), cervical VEMP amplitudes (r = 0.62, p <0.0001), air conduction thresholds at 250 Hz (r = 0.25, p = 0.043), and air-bone gap at 500 Hz (r = 0.27, p = 0.01) positively correlated with increasing size of dehiscence. An inverse relationship between cervical VEMP thresholds (r = -0.56, p < 0.0001) and surface area of the dehiscence was observed. No association between dizziness handicap and surface area was identified. Among patients with confirmed SCD, ocular and cervical VEMP amplitudes, cervical VEMP thresholds, and air conduction thresholds at 250 Hz are significantly correlated with the surface area of the dehiscence.

BILATERAL RETINOCHOROIDITIS CAUSED BY AN ATYPICAL STRAIN OF TOXOPLASMA GONDII

PubMed Central

Bottós, Juliana; Miller, Robin H.; Belfort, Rubens N.; Macedo, Ana Carolina; Belfort, Rubens; Grigg, Michael E.

2012-01-01

Background A 53-year-old man presented with an acute bilateral posterior uveitis with extensive necrotizing retinochoroiditis but without chorioretinal scarring. A thorough workup did not reveal any underlying disease. The possibilities of atypical ocular toxoplasmosis as well as herpetic retinal necrosis were considered and specific therapy instituted, with little improvement. The patient died within two months as result of an undifferentiated squamous cell carcinoma. Methods Histopathological examination, immunohistochemistry and multi-locus polymerase chain reaction confirmed T. gondii infection of the retina Results Macroscopic examination of enucleated globe showed extensive retinal necrosis and vitreous detachment. Histological examination of retinal tissue identified numerous round–to-elliptical toxoplasmic cysts within the retina, with retinal necrosis and minimal choroidal inflammation. Immunohistochemical analyses confirmed the cysts were due to Toxoplasma gondii. DNA extracted from formalin-fixed, paraffin-embedded tissue sections was subjected to multi-locus PCR analysis at the following typing loci: SAG1, SAG2, SAG3, SAG4, B1, NTS2, GRA6, and GRA7. DNA sequencing of positive PCR products at the NTS2, SAG1, and GRA7 loci confirmed the presence of a non-archetypal strain of T. gondii infecting the eye of the patient experiencing a severe, atypical ocular toxoplasmosis Conclusion A highly divergent, non-archetypal strain of Toxoplasma gondii was responsible for causing a severe, atypical bilateral retinochoroiditis in a patient from Brazil. PMID:19666926

Amniotic membrane transplantation for corneal surface reconstruction after excision of corneolimbal squamous cell carcinomas in nine horses.

PubMed

Ollivier, F J; Kallberg, M E; Plummer, C E; Barrie, K P; O'Reilly, S; Taylor, D P; Gelatt, K N; Brooks, D E

2006-01-01

The purpose of this study was to evaluate the usefulness and effectiveness of permanent amniotic membrane transplantation as an adjunctive treatment to superficial keratectomy alone or combined with strontium-90 irradiation for treatment of equine corneolimbal squamous cell carcinoma (SCC) to decrease corneal scarring and recurrence rate. The retrospective case study included 11 horses (n = 12 eyes) diagnosed and treated for ocular SCC that involved the limbus and cornea. Nine of those horses (n = 9 eyes) were treated between 2002 and 2006, with superficial lamellar keratectomy alone or combined with strontium-90 irradiation and followed by placement of a permanent amniotic membrane graft in the surgical defect. The level of scarring (i.e. the clarity of the cornea) resulting with the use of amniotic membrane was subjectively compared to cases where a permanent bulbar conjunctival graft was performed following keratectomy combined with strontium-90 irradiation or cryotherapy (n = 3 eyes). Recurrence was defined as the postoperative and postirradiation regrowth of SCC in the same site and globe. The nine horses that received an amniotic membrane graft after keratectomy alone or combined with irradiation showed a minimal level of scarring in a cornea that regained a greater transparency in comparison to the horses that were treated with a bulbar conjunctival graft. All of the horses that received an amniotic membrane graft had 226 +/- 218 days of follow-up without tumor recurrence (mean +/- SD), ranging from 21 days to 778 days. The combination of superficial keratectomy alone or associated with beta-irradiation and permanent amniotic membrane transplantation is an effective treatment of corneal or corneolimbal SCC in horses. The placement of an amniotic membrane material represents an alternative surgical procedure to bulbar conjunctival grafts, especially if there is a lack of bulbar conjunctiva tissue available after tumor resection or if a particularly large corneal resection is necessary. The amniotic membrane is incorporated into the corneal defect and seems to create noticeably much less scarring than a corneal defect covered by bulbar conjunctiva.

TFOS DEWS II Definition and Classification Report.

PubMed

Craig, Jennifer P; Nichols, Kelly K; Akpek, Esen K; Caffery, Barbara; Dua, Harminder S; Joo, Choun-Ki; Liu, Zuguo; Nelson, J Daniel; Nichols, Jason J; Tsubota, Kazuo; Stapleton, Fiona

2017-07-01

The goals of the TFOS DEWS II Definition and Classification Subcommittee were to create an evidence-based definition and a contemporary classification system for dry eye disease (DED). The new definition recognizes the multifactorial nature of dry eye as a disease where loss of homeostasis of the tear film is the central pathophysiological concept. Ocular symptoms, as a broader term that encompasses reports of discomfort or visual disturbance, feature in the definition and the key etiologies of tear film instability, hyperosmolarity, and ocular surface inflammation and damage were determined to be important for inclusion in the definition. In the light of new data, neurosensory abnormalities were also included in the definition for the first time. In the classification of DED, recent evidence supports a scheme based on the pathophysiology where aqueous deficient and evaporative dry eye exist as a continuum, such that elements of each are considered in diagnosis and management. Central to the scheme is a positive diagnosis of DED with signs and symptoms, and this is directed towards management to restore homeostasis. The scheme also allows consideration of various related manifestations, such as non-obvious disease involving ocular surface signs without related symptoms, including neurotrophic conditions where dysfunctional sensation exists, and cases where symptoms exist without demonstrable ocular surface signs, including neuropathic pain. This approach is not intended to override clinical assessment and judgment but should prove helpful in guiding clinical management and research. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnosis of X-Linked Hypohidrotic Ectodermal Dysplasia by Meibography and Infrared Thermography of the Eye.

PubMed

Kaercher, Thomas; Dietz, Jasna; Jacobi, Christina; Berz, Reinhold; Schneider, Holm

2015-09-01

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of ectodermal dysplasia. Clinical characteristics include meibomian gland disorder and the resulting hyperevaporative dry eye. In this study, we evaluated meibography and ocular infrared thermography as novel methods to diagnose XLHED. Eight infants, 12 boys and 14 male adults with XLHED and 12 healthy control subjects were subjected to a panel of tests including the ocular surface disease index (OSDI), meibography and infrared thermography, non-invasive measurement of tear film break-up time (NIBUT) and osmolarity, Schirmer's test, lissamine green staining and fluorescein staining. Sensitivity and specificity were determined for single tests and selected test combinations. Meibography had 100% sensitivity and specificity for identifying XLHED. Infrared thermography, a completely non-invasive procedure, revealed a typical pattern for male subjects with XLHED. It was, however, less sensitive (86% for adults and 67% for children) than meibography or a combination of established routine tests. In adults, OSDI and NIBUT were the best single routine tests (sensitivity of 86% and 71%, respectively), whereas increased tear osmolarity appeared as a rather unspecific ophthalmic symptom. In children, NIBUT was the most convincing routine test (sensitivity of 91%). Meibography is the most reliable ophthalmic examination to establish a clinical diagnosis in individuals with suspected hypohidrotic ectodermal dysplasia, even before genetic test results are available. Tear film tests and ocular surface staining are less sensitive in children, but very helpful for estimating the severity of ocular surface disease in individuals with known XLHED.

Cicatricial changes in ocular pemphigus

PubMed Central

Chirinos-Saldaña, P; Zuñiga-Gonzalez, I; Hernandez-Camarena, J C; Navas, A; Ramirez-Luquin, T; Robles-Contreras, A; Jimenez-Martinez, M C; Ramirez-Miranda, A; Bautista-de Lucio, V M; Graue-Hernandez, E O

2014-01-01

Purpose To describe the clinical characteristics of ocular involvement in patients with pemphigus at an ophthalmological referral center. Methods A retrospective review was conducted on patients with the immunopathological diagnosis of pemphigus examined between 1 January 2000 and 1 April 2010. Uncorrected distance visual acuity (UDVA), best corrected distance visual acuity (BCVA), ocular symptoms, and ocular surface inflammatory and scarring changes were assessed. Results A total of 15 patients were identified, with a mean age of 68.27±14.35 years, and 80% (n=12) were female. Extraocular involvement was reported in one patient. All of the eyes showed cicatricial changes in the conjunctiva. In all, 6 eyes (20%) were classified as stage I; 12 eyes (40%) as stage II; 10 eyes (33%) as stage III; and 2 eyes (7%) as stage IV. A statistically significant association was found between BCVA and the severity of ocular involvement. The mean BCVA logMAR was 1.66 (20/914), with a range from logMAR 0 (20/20) to logMAR 4 (NLP). Other ocular diseases were found in 8 (53.3%), systemic diseases in 10 (66.7%), and the use of pemphigus-inducing drugs in 10 patients (66.7%). Conclusions The present report represents the largest series of ocular involvement in pemphigus confirmed by immunopathology. The clinical manifestations varied from conjunctival hyperemia to corneal scarring and perforation. There was a strong association between scarring changes and low BCVA. Ocular and systemic diseases as well as the use of pemphigus-inducing drugs may predispose to ocular cicatricial changes observed in this series. PMID:24480839

Spontaneous Blinking from a Tribological Viewpoint.

PubMed

Pult, Heiko; Tosatti, Samuele G P; Spencer, Nicholas D; Asfour, Jean-Michel; Ebenhoch, Michael; Murphy, Paul J

2015-07-01

The mechanical forces between the lid wiper and the ocular surface, and between a contact lens and the lid wiper, are reported to be related to dry eye symptoms. Furthermore, the mechanical forces between these sliding partners are assumed to be related to the ocular signs of lid-wiper epitheliopathy (LWE) and lid-parallel conjunctival folds (LIPCOF). Recent literature provides some evidence that a contact lens with a low coefficient of friction (CoF) improves wearing comfort by reducing the mechanical forces between the contact lens surface and the lid wiper. This review discusses the mechanical forces during spontaneous blinks from a tribological perspective, at both low and high sliding velocities, in a healthy subject. It concludes that the coefficient of friction of the ocular surfaces appears to be strongly comparable to that of hydrophilic polymer brushes at low sliding velocity, and that, with increased sliding velocity, there is no wear at the sliding partners' surfaces thanks to the presence of a fluid film between the two sliding partners. In contrast, in the case of dry eye, the failure to maintain a full fluid film lubrication regime at high blinking speeds may lead to increased shear rates, resulting in deformation and wear of the sliding pairs. These shear rates are most likely related to tear film viscosity. Copyright © 2015 Elsevier Inc. All rights reserved.

Microbial contamination of contact lenses, lens care solutions, and their accessories: a literature review.

PubMed

Szczotka-Flynn, Loretta B; Pearlman, Eric; Ghannoum, Mahmoud

2010-03-01

A contact lens (CL) can act as a vector for microorganisms to adhere to and transfer to the ocular surface. Commensal microorganisms that uneventfully cohabitate on lid margins and conjunctivae and potential pathogens that are found transiently on the ocular surface can inoculate CLs in vivo. In the presence of reduced tissue resistance, these resident microorganisms or transient pathogens can invade and colonize the cornea or conjunctiva to produce inflammation or infection. The literature was reviewed and used to summarize the findings over the last 30 years on the identification, enumeration, and classification of microorganisms adherent to CLs and their accessories during the course of normal wear and to hypothesize the role that these microorganisms play in CL infection and inflammation. Lens handling greatly increases the incidence of lens contamination, and the ocular surface has a tremendous ability to destroy organisms. However, even when removed aseptically from the eye, more than half of lenses are found to harbor microorganisms, almost exclusively bacteria. Coagulase-negative Staphylococci are most commonly cultured from worn lenses; however, approximately 10% of lenses harbor Gram-negative and highly pathogenic species, even in asymptomatic subjects. In storage cases, the incidence of positive microbial bioburden is also typically greater than 50%. All types of care solutions can become contaminated, including up to 30% of preserved products. The process of CL-related microbial keratitis and inflammation is thought to be preceded by the presence or transfer or both of microorganisms from the lens to the ocular surface. Thus, this detailed understanding of lens-related bioburden is important in the understanding of factors associated with infectious and inflammatory complications. Promising mechanisms to prevent bacterial colonization on lenses and lens cases are forthcoming, which may decrease the incidence of microbially driven CL complications.

Effects of Menthol-Containing Artificial Tears on Tear Stimulation and Ocular Surface Integrity in Normal and Dry Eye Rat Models.

PubMed

Ahn, Somin; Eom, Youngsub; Kang, Boram; Park, Jungboung; Lee, Hyung Keun; Kim, Hyo Myung; Song, Jong Suk

2018-05-01

To evaluate the effects of menthol-containing artificial tears on tear stimulation and ocular surface integrity in normal and dry eye rat models. A total of 54 male Lewis rats were used. The levels of tear secretion and tear MUC5AC concentrations were compared between the menthol-containing artificial tear-treated group (menthol group) and the vehicle-treated group (vehicle group). The groups were compared after a single instillation to evaluate the immediate effects, and after repeated instillation (five times a day for 5 days) to evaluate the longer-term effects. Tear lactate dehydrogenase (LDH) activity was measured to evaluate eye drop instillation-induced ocular surface damage. The effects of menthol-containing artificial tears were also evaluated in a dry eye rat model. After a single instillation of menthol-containing artificial tears, tear secretion increased from 4.37 (±0.75) mm at baseline to 7.37 (±1.60) mm. However, after repeated instillations, the effects of tear stimulation decreased. The tear MUC5AC concentration was significantly lower in the menthol group than in the vehicle group after a single instillation, but not after repeated instillation. However, the tear LDH concentration was significantly increased in the menthol group after repeated instillation. In the dry eye rat model, the extent of menthol-induced tear stimulation was reduced. Menthol-containing artificial tears increased tear secretion, but lowered the tear MUC5AC concentration. Menthol-induced tear stimulation was reduced after repeated instillation for 5 days and in the dry eye rat model. Conversely, repeated instillation of menthol-induced ocular surface damage, resulting in increased tear LDH activity.

Regional differences in rat conjunctival ion transport activities

PubMed Central

Yu, Dongfang; Thelin, William R.; Rogers, Troy D.; Stutts, M. Jackson; Randell, Scott H.; Grubb, Barbara R.

2012-01-01

Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na+ transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface. PMID:22814399

Effects of silicone hydrogel contact lenses on ocular surface after Sub-Bowman's Keratomileusis.

PubMed

Gao, Shaohui; Wu, Junshu; Li, Lili; Wang, Yong; Zhong, Xingwu

2013-11-01

To evaluate the efficacy of silicone hydrogel contact lenses on ocular surface after Sub-Bowman Keratomileusis (SBK). Forty-six patients suffered from myopia underwent a bilateral SBK. Post-operatively, one eye of each patient wore a PureVision contact lens for 24 h as a treated eye and the contralateral eye was as a blank control. Afterwards, corneal fluorescein (FL) staining, tear break-up time (TBUT), schirmer I test (SIT), central corneal thickness (CCT), ocular surface disease index (OSDI), corneal hysteresis (CH), corneal resistance factor (CRF) and corneal flap complications were assessed 1 d (except for CH and CRF), 1 week, 1 month and 3 months postoperatively. Following SBK, in contrast to the control, corneal fluorescein staining of treated eyes were significantly reduced and tear break-up time of treated eyes were significantly improved at 1 d and 1 week after SBK. However, Schirmer I test of treated and control eyes were not different after SBK. Central corneal thickness of treated eyes were significantly thinner than that of control at 1 d after SBK, however, there were no differences at other time points. Ocular surface disease index of treated eyes were obviously alleviated more than that of control at 1 d after SBK, but no differences were found at other visits. Moreover, Corneal hysteresis and corneal resistance factor of treated and un-treated eyes were not different after surgery. And also the rate of corneal flap complications were not different between treated and control eyes after SBK. Silicone hydrogel contact lenses played a positive role in accelerating corneal epithelial healing, enhancing tear film stability and reducing discomfort of patients in the early stage after SBK.

The relation of functional visual acuity measurement methodology to tear functions and ocular surface status.

PubMed

Kaido, Minako; Ishida, Reiko; Dogru, Murat; Tsubota, Kazuo

2011-09-01

To investigate the relation of functional visual acuity (FVA) measurements with dry eye test parameters and to compare the testing methods with and without blink suppression and anesthetic instillation. A prospective comparative case series. Thirty right eyes of 30 dry eye patients and 25 right eyes of 25 normal subjects seen at Keio University School of Medicine, Department of Ophthalmology were studied. FVA testing was performed using a FVA measurement system with two different approaches, one in which measurements were made under natural blinking conditions without topical anesthesia (FVA-N) and the other in which the measurements were made under the blink suppression condition with topical anesthetic eye drops (FVA-BS). Tear function examinations, such as the Schirmer test, tear film break-up time, and fluorescein and Rose Bengal vital staining as ocular surface evaluation, were performed. The mean logMAR FVA-N scores and logMAR Landolt visual acuity scores were significantly lower in the dry eye subjects than in the healthy controls (p < 0.05), while there were no statistical differences between the logMAR FVA-BS scores of the dry eye subjects and those of the healthy controls. There was a significant correlation between the logMAR Landolt visual acuities and the logMAR FVA-N and logMAR FVA-BS scores. The FVA-N scores correlated significantly with tear quantities, tear stability and, especially, the ocular surface vital staining scores. FVA measurements performed under natural blinking significantly reflected the tear functions and ocular surface status of the eye and would appear to be a reliable method of FVA testing. FVA measurement is also an accurate predictor of dry eye status.

Cytokine and chemokine levels in tears from healthy subjects.

PubMed

Carreño, Ester; Enríquez-de-Salamanca, Amalia; Tesón, Marisa; García-Vázquez, Carmen; Stern, Michael E; Whitcup, Scott M; Calonge, Margarita

2010-11-01

There is growing evidence for the existence of an 'immune tone' in normal tears. The aim of this study was to determine the levels of a large panel of cytokines and chemokines in tears obtained from healthy subjects. These levels can then serve as baseline values for comparison with patients suffering from ocular surface diseases. Nine healthy subjects participated in this study, and normal ocular surface health was documented by the results of a dry eye questionnaire, Schirmer strip wetting, and vital staining of the cornea. Four microliters of tears were collected from each eye and analysed separately with multiplex bead-based assays for the concentration of 30 cytokines and chemokines. Twenty-five cytokines/chemokines were detected. CCL11/Eotaxin1, GM-CSF, G-CSF, IFN-γ, IL-2, IL-3, IL-4, IL-5, IL-10, IL-13, IL-12p70, IL-15, CX3CL1/Fractalkine, TNF-α, epidermal growth factor, and CCL4/MIP-1β were present at 5-100 pg/ml. IL-1β, IL-6, IL-7A, CXCL8/IL-8, and CCL2/MCP-1 were present at 100-400 pg/ml. IL-1Ra, CXCL10/IP-10 and vascular endothelial growth factor were present at more than 1000 pg/ml. Multiplex bead-based assays are convenient for cytokine/chemokine detection in tears. Fracktalkine has been detected in human healthy tears for the first time. The knowledge of cytokine/chemokine concentrations in tears from normal subjects is an important reference for further comparison with patients suffering from ocular surface diseases. Variability in their levels can reflect a phenomenon of potential importance for the understanding of the ocular surface cytokine pattern. © 2010 The Authors. Journal compilation © 2010 Acta Ophthalmol.

Influence of femtosecond lenticule extraction and small incision lenticule extraction on corneal nerve density and ocular surface: a 1-year prospective, confocal, microscopic study.

PubMed

Ishii, Rie; Shimizu, Kimiya; Igarashi, Akihito; Kobashi, Hidenaga; Kamiya, Kazutaka

2015-01-01

To compare the influence of femtosecond lenticule extraction (FLEx) and small incision lenticule extraction (SMILE) on corneal nerve density and the ocular surface for equivalent degrees of correction of myopia. Sixty eyes of 30 patients (8 males and 22 females, mean age: 31.0 ± 6.0 years) were included in the study. The patients underwent FLEx in 1 eye and SMILE in the other eye by random assignment. Subbasal nerve density was measured using confocal microscopy preoperatively and at 1 week, 1 and 3 months, and 1 year postoperatively. Ocular surface parameters such as Schirmer's test results, tear film break-up time, and corneal sensation were performed preoperatively and at 1 and 3 months postoperatively. In the FLEx group, subbasal nerve density was 18,390 ± 6,090 µm/mm(2) preoperatively and 5,770 ± 3,490 µm/mm(2) at 1 year postoperatively (P < .001, Dunnett's test). In the SMILE group, subbasal nerve density was 16,810 ± 6,220 µm/mm(2) preoperatively and 11,870 ± 8,200 µm/mm(2) at 1 year postoperatively (P = .21). The decrease in corneal nerve density was significantly less after SMILE than after FLEx at all postoperative visits (Mann-Whitney U test, P < .05). FLEx resulted in a significant decrease in Schirmer's test results, tear film break-up time, and corneal sensation at all postoperative visits, whereas SMILE induced no significant changes in these parameters (P > .05). There was less damage to the sub-basal nerve plexus of the cornea and less effect on the ocular surface parameters after SMILE than after FLEx. Copyright 2015, SLACK Incorporated.

Regional differences in rat conjunctival ion transport activities.

PubMed

Yu, Dongfang; Thelin, William R; Rogers, Troy D; Stutts, M Jackson; Randell, Scott H; Grubb, Barbara R; Boucher, Richard C

2012-10-01

Active ion transport and coupled osmotic water flow are essential to maintain ocular surface health. We investigated regional differences in the ion transport activities of the rat conjunctivas and compared these activities with those of cornea and lacrimal gland. The epithelial sodium channel (ENaC), sodium/glucose cotransporter 1 (Slc5a1), transmembrane protein 16 (Tmem16a, b, f, and g), cystic fibrosis transmembrane conductance regulator (Cftr), and mucin (Muc4, 5ac, and 5b) mRNA expression was characterized by RT-PCR. ENaC proteins were measured by Western blot. Prespecified regions (palpebral, fornical, and bulbar) of freshly isolated conjunctival tissues and cell cultures were studied electrophysiologically with Ussing chambers. The transepithelial electrical potential difference (PD) of the ocular surface was also measured in vivo. The effect of amiloride and UTP on the tear volume was evaluated in lacrimal gland excised rats. All selected genes were detected but with different expression patterns. We detected αENaC protein in all tissues, βENaC in palpebral and fornical conjunctiva, and γENaC in all tissues except lacrimal glands. Electrophysiological studies of conjunctival tissues and cell cultures identified functional ENaC, SLC5A1, CFTR, and TMEM16. Fornical conjunctiva exhibited the most active ion transport under basal conditions amongst conjunctival regions. PD measurements confirmed functional ENaC-mediated Na(+) transport on the ocular surface. Amiloride and UTP increased tear volume in lacrimal gland excised rats. This study demonstrated that the different regions of the conjunctiva exhibited a spectrum of ion transport activities. Understanding the specific functions of distinct regions of the conjunctiva may foster a better understanding of the physiology maintaining hydration of the ocular surface.

Improvements in Topical Ocular Drug Delivery Systems: Hydrogels and Contact Lenses.

PubMed

Ribeiro, Andreza Maria; Figueiras, Ana; Veiga, Francisco

2015-01-01

Conventional ophthalmic systems present very low corneal systemic bioavailability due to the nasolacrimal drainage and the difficulty to deliver the drug in the posterior segment of ocular tissue. For these reasons, recent advances have focused on the development of new ophthalmic drug delivery systems. This review provides an insight into the various constraints associated with ocular drug delivery, summarizes recent findings in soft contact lenses (SCL) and the applications of novel pharmaceutical systems for ocular drug delivery. Among the new therapeutic approaches in ophthalmology, SCL are novel continuous-delivery systems, providing high and sustained levels of drugs to the cornea. The tendency of research in ophthalmic drug delivery systems development are directed towards a combination of several technologies (bio-inspired and molecular imprinting techniques) and materials (cyclodextrins, surfactants, specific monomers). There is a tendency to develop systems which not only prolong the contact time of the vehicle at the ocular surface, but also at the same time slow down the clearance of the drug. Different materials can be applied during the development of contact lenses and can be combined with natural inspired strategies of drug immobilization and release, providing successful tools for ocular drug delivery systems.

Dry Eye: an Inflammatory Ocular Disease

PubMed Central

Hessen, Michelle; Akpek, Esen Karamursel

2014-01-01

Keratoconjunctivitis sicca, or dry eye, is a common ocular disease prompting millions of individuals to seek ophthalmological care. Regardless of the underlying etiology, dry eye has been shown to be associated with abnormalities in the pre-corneal tear film and subsequent inflammatory changes in the entire ocular surface including the adnexa, conjunctiva and cornea. Since the recognition of the role of inflammation in dry eye, a number of novel treatments have been investigated designed to inhibit various inflammatory pathways. Current medications that are used, including cyclosporine A, corticosteroids, tacrolimus, tetracycline derivatives and autologous serum, have been effective for management of dry eye and lead to measurable clinical improvement. PMID:25279127

Development of ocular drug delivery systems using molecularly imprinted soft contact lenses.

PubMed

Tashakori-Sabzevar, Faezeh; Mohajeri, Seyed Ahmad

2015-05-01

Recently, significant advances have been made in order to optimize drug delivery to ocular tissues. The main problems in ocular drug delivery are poor bioavailability and uncontrollable drug delivery of conventional ophthalmic preparations (e.g. eye drops). Hydrogels have been investigated since 1965 as new ocular drug delivery systems. Increase of hydrogel loading capacity, optimization of drug residence time on the ocular surface and biocompatibility with the eye tissue has been the main focus of previous studies. Molecular imprinting technology provided the opportunity to fulfill the above-mentioned objectives. Molecularly imprinted soft contact lenses (SCLs) have high potentials as novel drug delivery systems for the treatment of eye disorders. This technique is used for the preparation of polymers with specific binding sites for a template molecule. Previous studies indicated that molecular imprinting technology could be successfully applied for the preparation of SCLs as ocular drug delivery systems. Previous research, particularly in vivo studies, demonstrated that molecular imprinting is a versatile and effective method in optimizing the drug release behavior and enhancing the loading capacity of SCLs as new ocular drug delivery systems. This review highlights various potentials of molecularly imprinted contact lenses in enhancing the drug-loading capacity and controlling the drug release, compared to other ocular drug delivery systems. We have also studied the effects of contributing factors such as the type of comonomer, template/functional monomer molar ratio, crosslinker concentration in drug-loading capacity, and the release properties of molecularly imprinted hydrogels.

A mass and solute balance model for tear volume and osmolarity in the normal and the dry eye.

PubMed

Gaffney, E A; Tiffany, J M; Yokoi, N; Bron, A J

2010-01-01

Tear hyperosmolarity is thought to play a key role in the mechanism of dry eye, a common symptomatic condition accompanied by visual disturbance, tear film instability, inflammation and damage to the ocular surface. We have constructed a model for the mass and solute balance of the tears, with parameter estimation based on extensive data from the literature which permits the influence of tear evaporation, lacrimal flux and blink rate on tear osmolarity to be explored. In particular the nature of compensatory events has been estimated in aqueous-deficient (ADDE) and evaporative (EDE) dry eye. The model reproduces observed osmolarities of the tear meniscus for the healthy eye and predicts a higher concentration in the tear film than meniscus in normal and dry eye states. The differential is small in the normal eye, but is significantly increased in dry eye, especially for the simultaneous presence of high meniscus concentration and low meniscus radius. This may influence the interpretation of osmolarity values obtained from meniscus samples since they need not fully reflect potential damage to the ocular surface caused by tear film hyperosmolarity. Interrogation of the model suggests that increases in blink rate may play a limited role in compensating for a rise in tear osmolarity in ADDE but that an increase in lacrimal flux, together with an increase in blink rate, may delay the development of hyperosmolarity in EDE. Nonetheless, it is predicted that tear osmolarity may rise to much higher levels in EDE than ADDE before the onset of tear film breakup, in the absence of events at the ocular surface which would independently compromise tear film stability. Differences in the predicted responses of the pre-ocular tears in ADDE compared to EDE or hybrid disease to defined conditions suggest that no single, empirically-accessible variable can act as a surrogate for tear film concentration and the potential for ocular surface damage. This emphasises the need to measure and integrate multiple diagnostic indicators to determine outcomes and prognosis. Modelling predictions in addition show that further studies concerning the possibility of a high lacrimal flux phenotype in EDE are likely to be profitable.

Long term safety and tolerability of Tafluprost 0.0015% vs Timolol 0.1% preservative-free in ocular hypertensive and in primary open-angle glaucoma patients: a cross sectional study.

PubMed

Rolle, Teresa; Spinetta, Roberta; Nuzzi, Raffaele

2017-08-03

The effects of preservatives of antiglaucoma medications on corneal surface and tear function have been widely shown in literature; it's not the same as regards the active compounds themselves. The purpose of our study was to compare Ocular Surface Disease (OSD) signs and symptoms of Tafluprost 0.0015% versus preservative free (PF) Timolol 0.1% eyedrops in ocular hypertensive (OH) and in primary open-angle glaucoma (POAG) patients. A cross-sectional study included patients in monotherapy for at least 36 months with Tafluprost 0.0015% (27) or PF Timolol 0.1% (24) and 20 healthy age and sex-matched volunteers. All subjects underwent clinical tests (Schirmer I and break-up time), in vivo confocal microscopy (IVCM) and were surveyed using Ocular Surface Disease Index (OSDI) and Glaucoma Symptoms Scale (GSS) questionnaires. The groups were compared with ANOVA, Kruskal-Wallis test, t-test, Mann-Whitney test and Bonferroni's adjustment of p-values. No significant differences were found in questionnaires scores, clinical tests, IVCM variables between therapy groups. Tafluprost 0.0015% group showed significantly higher OSDI score, basal epithelial cells density, stromal reflectivity, sub-basal nerves tortuosity (p = 0.0000, 0.037, 0.006, 0.0000) and less GSS score, number of sub-basal nerves (p = 0.0000, 0.037) than controls but similar clinical tests results (p > 0.05). PF Timolol group had significantly higher OSDI score, basal epithelial cells density, stromal reflectivity and sub-basal nerve tortuosity (p = 0.000, 0.014, 0.008, 0.002), less GSS score, BUT and number of sub-basal nerves (p = 0.0000, 0.026, 0.003) than controls. Compared to PF Timolol 0.1%, Tafluprost 0.0015% showed similar safety with regards to tear function and corneal status and a similar tolerability profile. Both therapy groups show some alterations in corneal microstructure but no side effects on tear function except for an increased tear instability in PF Timolol 0.1% group. Ophtalmologists should be aware that even PF formulations may lead to a mild ocular surface impairment.

Interpreting the corneal response to oxygen: Is there a basis for re-evaluating data from gas-goggle studies?

PubMed

Papas, Eric B; Sweeney, Deborah F

2016-10-01

When anoxia (0% oxygen) is created within a gas-tight goggle, ocular physiological responses, including corneal swelling, limbal hyperaemia and pH change, are known to vary, depending on the presence or absence of a low, oxygen transmissibility contact lens. A new theory is proposed to account for this discrepancy based on the concept of lid derived oxygen, whereby oxygen originating from the vascular plexus of the palpebral conjunctiva supplements that available to the ocular surface in an open, normally blinking eye, even when the surrounding gaseous atmosphere is anoxic. The effect of a lid derived contribution to corneal oxygenation was assessed by using existing experimental data to model open-eye, corneal swelling behavior as a function of atmospheric oxygen content, both with and without the presence of a contact lens. These models predict that under atmospheric anoxia, contact lens wear results in 13.2% corneal swelling compared with only 5.4% when the lens was absent. Lid derived oxygen acts to provide the ocular surface in the non-contact lens wearing, normally blinking, open-eye with up to 4.7% equivalent oxygen concentration, even within the anoxic environment of a nitrogen filled goggle. Correcting for lid derived oxygen eliminates previously observed discrepancies in corneal swelling behavior and harmonizes the models for the contact lens wearing and gas-goggle cases. On this basis it is proposed that true anoxia at the ocular surface cannot be achieved by atmospheric manipulation (i.e. a gas-goggle) alone but requires an additional presence, e.g. a low, oxygen transmissibility contact lens, to prevent access to oxygen from the eyelids. Data from previously conducted experiments in which the gas-goggle paradigm was used, may have been founded on underestimates of the real oxygen concentration acting on the ocular surface at the time and if so, will require re-interpretation. Future work in this area should consider if a correction for lid derived oxygen is necessary. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dry Eye Disease: Prevalence, Assessment, and Management.

PubMed

Rouen, Patricia A; White, Mary L

Dry eye disease is a chronic condition of the corneal surface marked by persistent symptoms of irritation or burning that can cause inflammatory damage to the cornea and conjunctiva if untreated. Common risk factors for this syndrome include advancing age, female sex, low humidity environments, systemic medications, and autoimmune disorders. Treatments to relieve symptoms include tear replacement, humidification, improved nutrition, and anti-inflammatory ocular agents. Home healthcare nurses can identify signs and symptoms of dry eye syndrome and initiate strategies that range from warm compresses to physician referrals for more aggressive treatment. Consistent management of this condition improves quality of life and minimizes damage to the ocular surface.

Diabetic corneal neuropathy: clinical perspectives.

PubMed

Bikbova, Guzel; Oshitari, Toshiyuki; Baba, Takayuki; Bikbov, Mukharram; Yamamoto, Shuichi

2018-01-01

Diabetic keratopathy is characterized by impaired innervation of the cornea that leads to decreased sensitivity, with resultant difficulties with epithelial wound healing. These difficulties in wound healing put patients at risk for ocular complications such as surface irregularities, corneal infections, and stromal opacification. Pathological changes in corneal innervations in diabetic patients are an important early indicator of diabetic neuropathy. The decrease in corneal sensitivity is strongly correlated with the duration of diabetes as well as the severity of the neuropathy. This review presents recent findings in assessing the ocular surface as well as the recent therapeutic strategies for optimal management of individuals with diabetes who are susceptible to developing diabetic neuropathy.

The Effect of Rebamipide on Ocular Surface Disorders Induced by Latanoprost and Timolol in Glaucoma Patients.

PubMed

Tokuda, Naoto; Kitaoka, Yasushi; Matsuzawa, Akiko; Miyamoto, Junsuke; Sakae, Shinsuke; Munemasa, Yasunari; Takagi, Hitoshi

2015-01-01

Purpose. To examine the efficacy of ophthalmic rebamipide suspensions on ocular surface disorders induced by antiglaucoma eye drops. Patients and Methods. Forty eyes of 40 patients receiving latanoprost (0.005%) and timolol (0.5%) were included in this randomized prospective study. The patients were randomly divided into two groups (n = 20): the rebamipide-treated group and control group. Changes in intraocular pressure, tear film break-up time (TBUT), and corneal epithelial barrier function were evaluated at baseline, 4 weeks, and 8 weeks after rebamipide administration. Furthermore, superficial punctate keratopathy severity was evaluated by scoring the lesion area and density. Results. There was no significant difference in intraocular pressure before and after rebamipide treatment. However, corneal epithelial barrier function improved significantly 4 and 8 weeks after rebamipide treatment. TBUT was partially, but significantly, increased (P = 0.02) 8 weeks after rebamipide treatment, whereas no significant change was observed at 4 weeks. Additionally, a significant decrease in area and density of keratopathy was observed 8 weeks after rebamipide treatment but not at 4 weeks. The control group showed no significant difference compared to baseline. Conclusions. Our data suggests that rebamipide treatment may reduce the occurrence of drug-induced ocular surface disorder.

Rebamipide ophthalmic suspension for the treatment of dry eye syndrome: a critical appraisal

PubMed Central

Kashima, Tomoyuki; Itakura, Hirotaka; Akiyama, Hideo; Kishi, Shoji

2014-01-01

Rebamipide was initially developed and approved for use in treating gastric ulcers and lesions associated with gastritis. Discovery of its ability to increase gastric mucin led to investigations of its effect on ocular surface mucin and the subsequent development for use in dry eye patients. Investigations have confirmed that rebamipide increases corneal and conjunctival mucin-like substances along with improving corneal and conjunctival injury. Clinically, rebamipide ophthalmic suspensions can effectively treat tear deficiency and mucin-caused corneal epithelial damage, and can restore the microstructure responsible for tear stability. Topical rebamipide has also been shown to be effective in treating other ocular surface disorders such as lagophthalmos, lid wiper epitheliopathy, and persistent corneal erosion. Rebamipide’s ability to modify epithelial cell function, improve tear stability, and suppress inflammation in the absence of any known major side effects suggest that it may be a beneficial first drug of choice for severe dry eye treatment and other ocular surface disorders. This review summarizes the history and development of this innovative dry eye treatment from its initial use as an effective stomach medication to its current use in the treatment of dry eye in Japan. PMID:24940041

Dysfunctional tear syndrome: dry eye disease and associated tear film disorders - new strategies for diagnosis and treatment.

PubMed

Milner, Mark S; Beckman, Kenneth A; Luchs, Jodi I; Allen, Quentin B; Awdeh, Richard M; Berdahl, John; Boland, Thomas S; Buznego, Carlos; Gira, Joseph P; Goldberg, Damien F; Goldman, David; Goyal, Raj K; Jackson, Mitchell A; Katz, James; Kim, Terry; Majmudar, Parag A; Malhotra, Ranjan P; McDonald, Marguerite B; Rajpal, Rajesh K; Raviv, Tal; Rowen, Sheri; Shamie, Neda; Solomon, Jonathan D; Stonecipher, Karl; Tauber, Shachar; Trattler, William; Walter, Keith A; Waring, George O; Weinstock, Robert J; Wiley, William F; Yeu, Elizabeth

2017-01-01

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition.

[Effect of anti-inflammatory therapy on the treatment of dry eye syndrome].

PubMed

Mrukwa-Kominek, Ewa; Rogowska-Godela, Anna; Gierek-Ciaciura, Stanisława

2007-01-01

Dry eye syndrome is a common chronic disease; agents and strategies for its effective management are still lacking. The syndrome tends to be accompanied by ocular surface inflammation; therefore, the use of anti-inflammatory agents might prove beneficial. The authors present up-to-date guidelines, strategies, and efficacy of dry eye syndrome management, including anti-inflammatory treatment. As no diagnostic tests are now available to assess ocular surface inflammation severity, the right timing to launch an anti-inflammatory agent is difficult to determine. Patients with mild intermittent bouts of symptoms which can be alleviated with ophthalmic lubricants do not typically require anti-inflammatory therapy. The latter should be considered in those who do not respond to lubricating drops, obtain poor results on clinical tests, and show symptoms of ocular surface irritation (eg. conjunctivae redness). Anti-inflammatory treatment of dry eye syndrome may include short-term corticosteroids, cyclosporine A emulsion, oral tetracycline therapy, oral omega-3 fatty acid supplements, and autologous serum eye drops. Anti-inflammatory treatment should be safe and effective; potential benefits should be evaluated for each individual patient. The authors have reviewed the advantages of anti-inflammatory treatment in dry eye syndrome, presented in literature.

Preliminary effects of oral uridine on the ocular surface in dry eye patients.

PubMed

Chang, Ki Cheol; Oh, Joo Youn; In, Youn Seok; Kim, Mee Kum; Shin, Ki Cheul; Wee, Won Ryang; Lee, Jin Hak; Park, Myung Gyu

2009-08-01

We designed a randomized, double blinded, 3-months controlled prospective clinical study to investigate effects of oral uridine on the ocular surface in dry eye patients. Twenty-seven patients who diagnosed as dry eye with lower than 5 mm of wetting in the Schirmer strip, with corneal epithelial erosion and who completely followed-up till 3 months were enrolled. Corneal-conjunctival fluorescein staining, non-anesthetic Schirmer test, impression cytology, and Ocular Surface Disease Index (OSDI) were evaluated in the experimental and placebo groups at the baseline, 1 and 3 months after start of medication in a double blinded manner. Fluorescein stain score of the cornea was markedly decreased in oral uridine group compared to the placebo group at 3 months after medication (P=0.032, Mann-Whitney U test). The Schirmer wetting score for the oral uridine group was significantly increased (P=0.001, Wilcoxon signed rank test) at 3 months and its difference between two groups was statistically significant (P=0.030, Mann-Whitney U test). OSDI scores were significantly decreased at 1 and 3 months in treatment group. Oral uridine is effective in treatment of dry eyes.

Dysfunctional tear syndrome: dry eye disease and associated tear film disorders – new strategies for diagnosis and treatment

PubMed Central

Milner, Mark S.; Beckman, Kenneth A.; Luchs, Jodi I.; Allen, Quentin B.; Awdeh, Richard M.; Berdahl, John; Boland, Thomas S.; Buznego, Carlos; Gira, Joseph P.; Goldberg, Damien F.; Goldman, David; Goyal, Raj K.; Jackson, Mitchell A.; Katz, James; Kim, Terry; Majmudar, Parag A.; Malhotra, Ranjan P.; McDonald, Marguerite B.; Rajpal, Rajesh K.; Raviv, Tal; Rowen, Sheri; Shamie, Neda; Solomon, Jonathan D.; Stonecipher, Karl; Tauber, Shachar; Trattler, William; Walter, Keith A.; Waring, George O.; Weinstock, Robert J.; Wiley, William F.; Yeu, Elizabeth

2017-01-01

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition. PMID:28099212

Ocular surface changes in thyroid eye disease.

PubMed

Ismailova, Dilyara S; Fedorov, Anatoly A; Grusha, Yaroslav O

2013-04-01

To study the incidence and risk factors of ocular surface damage in thyroid eye disease (TED) and to determine histological changes underlying positive vital staining in this condition. Forty-six patients (92 eyes) with TED were included in this study. Routine ophthalmologic examination, Schirmer test I, vital staining and corneal sensitivity were performed. Fifteen patients with positive vital staining underwent impression cytology and incisional biopsy. Positive vital staining with lissamine green was observed in 56 eyes (60.9%), 30 patients (65.2%). The average degree of staining was 4.57 ± 0.44 (National Eye Institute Workshop grading system). Severe dry eye syndrome was found in 16%. The following histological changes of conjunctiva were revealed: significant epithelial dystrophy with cell polymorphism, goblet cells loss, excessive desquamation and epithelial keratinization with local leukocytic infiltration of substantia propria. According to our results dry eye syndrome is present in 65.2% of patients (60.9% eyes) with TED. Significant risk factors of ocular surface damage in TED were exophthalmos, lagophthalmos, palpebral fissure height and lower lid retraction. Positive conjunctival staining results from punctuate epithelial erosions and excessive desquamation of superficial cells. Histopathologic changes detected in conjunctiva consistent with dry eye and are not specific for TED.

Rebamipide ophthalmic suspension for the treatment of dry eye syndrome: a critical appraisal.

PubMed

Kashima, Tomoyuki; Itakura, Hirotaka; Akiyama, Hideo; Kishi, Shoji

2014-01-01

Rebamipide was initially developed and approved for use in treating gastric ulcers and lesions associated with gastritis. Discovery of its ability to increase gastric mucin led to investigations of its effect on ocular surface mucin and the subsequent development for use in dry eye patients. Investigations have confirmed that rebamipide increases corneal and conjunctival mucin-like substances along with improving corneal and conjunctival injury. Clinically, rebamipide ophthalmic suspensions can effectively treat tear deficiency and mucin-caused corneal epithelial damage, and can restore the microstructure responsible for tear stability. Topical rebamipide has also been shown to be effective in treating other ocular surface disorders such as lagophthalmos, lid wiper epitheliopathy, and persistent corneal erosion. Rebamipide's ability to modify epithelial cell function, improve tear stability, and suppress inflammation in the absence of any known major side effects suggest that it may be a beneficial first drug of choice for severe dry eye treatment and other ocular surface disorders. This review summarizes the history and development of this innovative dry eye treatment from its initial use as an effective stomach medication to its current use in the treatment of dry eye in Japan.

Biopharmaceutical profile of pranoprofen-loaded PLGA nanoparticles containing hydrogels for ocular administration.

PubMed

Abrego, Guadalupe; Alvarado, Helen; Souto, Eliana B; Guevara, Bessy; Bellowa, Lyda Halbaut; Parra, Alexander; Calpena, Ana; Garcia, María Luisa

2015-09-01

Two optimized pranoprofen-loaded poly-l-lactic-co glycolic acid (PLGA) nanoparticles (PF-F1NPs; PF-F2NPs) have been developed and further dispersed into hydrogels for the production of semi-solid formulations intended for ocular administration. The optimized PF-NP suspensions were dispersed in freshly prepared carbomer hydrogels (HG_PF-F1NPs and HG_PF-F2NPs) or in hydrogels containing 1% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone) in order to improve the ocular biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (NSAID), by prolonging the contact of the pranoprofen with the eye, increasing the drug retention in the organ and enhancing its anti-inflammatory and analgesic efficiency. Carbomer 934 has been selected as gel-forming polymer. The hydrogel formulations with or without azone showed a non-Newtonian behavior and adequate physicochemical properties for ocular instillation. The release study of pranoprofen from the semi-solid formulations exhibited a sustained release behavior. The results obtained from ex vivo corneal permeation and in vivo anti-inflammatory efficacy studies suggest that the ocular application of the hydrogels containing azone was more effective over the azone-free formulations in the treatment of edema on the ocular surface. No signs of ocular irritancy have been detected for the produced hydrogels. Copyright © 2015 Elsevier B.V. All rights reserved.

[Transplantation of autologous labial salivary glands for severe dry eye].

PubMed

Luo, Shun-rong; Zou, Liu-he; Yan, Chao; Pan, Zhi-qiang; Liu, Jing-ming; Chen, Zhi-yuan; Yin, Wei-hong

2013-01-01

Autologous labial salivary gland transplantation has been a promising alternative for the treatment of severe dry eye. In this article, we describe the results of the ocular surface changes after labial salivary gland transplantation and investigate the feasibility of this treatment. The results of this technique in 8 patients (eyes) who suffered from severe dry eye were prospectively analyzed after surgery (follow-up of 6 months). The best-corrected visual acuity, Schirmer I test, degree of discomfort, usage of pharmaceutical tear substitutes, tear interferometry and slit lamp examination were investigated at different time before and after surgery. All grafts remained viable and the survival rate is 100%. All patients showed significant increase in the Schirmer's test and they expressed great improvement in their ocular discomfort. The use of artificial tear substitutes was reduced because of the increased ocular surface lubrication. Although the authors' long-term experience still is limited, we believe that the procedure is a promising alternative approach for severe dry eye.

Dry Eye Syndrome in Menopause and Perimenopausal Age Group.

PubMed

Peck, Travis; Olsakovsky, Leslie; Aggarwal, Shruti

2017-01-01

Dry eye disease (DED) is a multifactorial ocular surface disease that causes symptoms of ocular pain, discomfort, and decreased visual acuity. It significantly affects quality of life of patients. It is more prevalent in the females and is being specifically in the menopausal and postmenopausal age group. This is believed to be due to the changes in balance of sex hormones. Sex hormones - estrogens and androgens - influence production of all components of the tear film including aqueous layer, lipid, and mucin. Various mechanisms such as decrease in hormonal levels, shift in feedback mechanisms, and changes in receptor receptivity interplay to alter the ocular surface homeostasis and subsequently result in DED. Several studies have suggested potential role of hormone replacement therapy in menopause-associated dry eye symptoms. The purpose of this review is to help the non ophthalmic physicians about DED encountered commonly in menopausal age group. It is important for primary care physicians to understand DED due to its high prevalence, often debilitating symptoms and the potentially preventable and treatable nature of the condition.

Impact of Eye Cosmetics on the Eye, Adnexa, and Ocular Surface.

PubMed

Ng, Alison; Evans, Katharine; North, Rachel V; Jones, Lyndon; Purslow, Christine

2016-07-01

Despite the fact that cosmetic products undergo rigorous testing to ensure they are safe for human use, some users report mild discomfort following their application. The cutaneous changes, such as allergic dermatitis, are well reported, but the ocular changes associated with eye cosmetic use are less so. Some pigmented cosmetic products may accumulate within the lacrimal system and conjunctivae over many years of use, but immediate reports of eye discomfort after application are most common. Changes to the tear film and its stability may occur shortly after application, and contact lens wearers can also be affected by lens spoliation from cosmetic products. Additionally, creams used in the prevention of skin aging are often applied around the eyes, and retinoids present in these formulations can have negative effects on meibomian gland function and may be a contributing factor to dry eye disease. The aim of this review is to summarize current knowledge regarding the impact of cosmetic products on the eye, ocular surface, and tear film.

Novel surface-modified nanostructured lipid carriers with partially deacetylated water-soluble chitosan for efficient ocular delivery.

PubMed

Tian, Baocheng; Luo, Qiuhua; Song, Shuangshuang; Liu, Dandan; Pan, Hao; Zhang, Wenji; He, Ling; Ma, Shilin; Yang, Xinggang; Pan, Weisan

2012-03-01

The objective of this study was to propose novel surface-modified nanostructured lipid carriers with partially deacetylated water-soluble chitosan (NLC-PDSC) as an efficient ocular delivery system to improve its transcorneal penetration and precorneal retention. PDSC with a deacetylation degree of around 50% was synthesized using an improved method. NLC loaded with flurbiprofen (FB) were prepared by melt emulsification method. They presented spherical morphology under both transmission electron microscope and scanning electron microscope. After coating with 0.15% (w/v) PDSC solution, the NLC showed a core-shell structure and a reversed zeta potential. The enhanced transcorneal penetration of the coated NLC was evaluated using isolated rabbit corneas, with significantly increased apparent permeability coefficient being 1.40- and 1.75-fold of the NLC and FB phosphate solution (FB-sol; p < 0.05), respectively. Precorneal retention assessed by gamma scintigraphy in vivo showed that the area under the remaining activity-time curve of the PDSC-coated formulation was 1.3-fold of the NLC and 2.4-fold of FB-sol. Moreover, in vivo ocular tolerance study indicated that there was no difference in irritation between the coated and noncoated NLC. In conclusion, novel NLC demonstrate high potential for ocular drug delivery. Copyright © 2011 Wiley Periodicals, Inc.

Implantation of refractive multifocal intraocular lens with a surface-embedded near section for cataract eyes complicated with a coexisting ocular pathology

PubMed Central

Ouchi, M; Kinoshita, S

2015-01-01

Purpose To evaluate the postoperative outcomes of cataract eyes complicated with coexisting ocular pathologies that underwent implantation of a refractive multifocal intraocular lens (MIOL) with a surface-embedded near section. Methods LENTIS MPlus (Oculentis GmbH) refractive MIOLs were implanted in 15 eyes with ocular pathologies other than cataract (ie, six high-myopia eyes with an axial length longer than 28 mm, two fundus albipunctatus eyes, two branch retinal-vein occlusion eyes, four glaucoma eyes (one with high myopia), and two keratoconus eyes). Uncorrected or corrected distance and near visual acuity (VA) (UDVA, UNVA, CDVA, and CNVA), contrast sensitivity, and defocus curve were measured at 1 day and 6 months postoperatively, and each patient completed a 6-month postoperative questionnaire regarding vision quality and eyeglass use. Results Thirteen eyes (87%) registered 0 or better in CDVA and 12 eyes (73%) registered better than 0 in CNVA. Contrast sensitivity in the eyes of all patients was comparable to that of normal healthy subjects. No patient required eyeglasses for distance vision, but three patients (20%) required them for near vision. No patient reported poor or very poor vision quality. Conclusion With careful case selection, sectorial refractive MIOL implantation is effective for treating cataract eyes complicated with ocular pathologies. PMID:25744442

Implantation of refractive multifocal intraocular lens with a surface-embedded near section for cataract eyes complicated with a coexisting ocular pathology.

PubMed

Ouchi, M; Kinoshita, S

2015-05-01

To evaluate the postoperative outcomes of cataract eyes complicated with coexisting ocular pathologies that underwent implantation of a refractive multifocal intraocular lens (MIOL) with a surface-embedded near section. LENTIS MPlus (Oculentis GmbH) refractive MIOLs were implanted in 15 eyes with ocular pathologies other than cataract (ie, six high-myopia eyes with an axial length longer than 28 mm, two fundus albipunctatus eyes, two branch retinal-vein occlusion eyes, four glaucoma eyes (one with high myopia), and two keratoconus eyes). Uncorrected or corrected distance and near visual acuity (VA) (UDVA, UNVA, CDVA, and CNVA), contrast sensitivity, and defocus curve were measured at 1 day and 6 months postoperatively, and each patient completed a 6-month postoperative questionnaire regarding vision quality and eyeglass use. Thirteen eyes (87%) registered 0 or better in CDVA and 12 eyes (73%) registered better than 0 in CNVA. Contrast sensitivity in the eyes of all patients was comparable to that of normal healthy subjects. No patient required eyeglasses for distance vision, but three patients (20%) required them for near vision. No patient reported poor or very poor vision quality. With careful case selection, sectorial refractive MIOL implantation is effective for treating cataract eyes complicated with ocular pathologies.

Ozone depletion and solar ultraviolet radiation: ocular effects, a United nations environment programme perspective.

PubMed

Cullen, Anthony P

2011-07-01

To describe he role played by the United Nations Environmental Effects Panel with respect to the ocular effects of stratospheric ozone depletion and present the essence of the Health Chapter of the 2010 Assessment. A consideration of solar ultraviolet radiation (UVR) at the Earth's surface as it is affected by atmospheric changes and how these influence sunlight-related eye diseases. A review of the current Assessment with emphasis on pterygium, cataract, ocular melanoma, and age-related macular degeneration. Although the ozone layer is projected to recover slowly in the coming decades, continuing vigilance is required regarding exposure to the sun. Evidence implicating solar UVR, especially UVB, in every tissue of the eye continues to be amassed. The need for ocular UV protection existed before the discovery of the depletion of the ozone layer and will continue even when the layer fully recovers in approximately 2100.

Glycobiology of ocular angiogenesis

PubMed Central

Markowska, Anna I; Cao, Zhiyi; Panjwani, Noorjahan

2014-01-01

Ocular neovascularization can affect almost all the tissues of the eye: the cornea, the iris, the retina, and the choroid. Pathological neovascularization is the underlying cause of vision loss in common ocular conditions such as diabetic retinopathy, retinopathy of prematurity and age-related macular neovascularization. Glycosylation is the most common covalent posttranslational modification of proteins in mammalian cells. A growing body of evidence demonstrates that glycosylation influences the process of angiogenesis and impacts activation, proliferation, and migration of endothelial cells as well as the interaction of angiogenic endothelial cells with other cell types necessary to form blood vessels. Recent studies have provided evidence that members of the galectin class of β-galactoside-binding proteins modulate angiogenesis by novel carbohydrate-based recognition systems involving interactions between glycans of angiogenic cell surface receptors and galectins. This review discusses the significance of glycosylation and the role of galectins in the pathogenesis of ocular neovascularization. PMID:25108228

Dry eye symptoms align more closely to non-ocular conditions than to tear film parameters.

PubMed

Galor, Anat; Felix, Elizabeth R; Feuer, William; Shalabi, Nabeel; Martin, Eden R; Margolis, Todd P; Sarantopoulos, Constantine D; Levitt, Roy C

2015-08-01

To evaluate the relationship between dry eye symptoms, non-ocular conditions and tear film parameters. Cross-sectional study. The study population consisted of patients who were seen in the Miami Veterans Affairs eye clinic. Patients filled out standardised questionnaires assessing dry eye symptoms (dry eye questionnaire 5 (DEQ5) and ocular surface disease index (OSDI)), non-ocular pain, depression and post-traumatic stress disorder (PTSD), and also underwent measurement of tear film parameters. Correlations between dry eye symptoms and non-ocular conditions as compared with tear film parameters. 136 patients with a mean age of 65 (SD 11) years participated in the study. All correlations between the dry eye questionnaire scores (DEQ5 and OSDI) and (A) self-reported non-ocular pain measures (numerical rating scale and pain history), (B) depression and (C) PTSD were significant and moderate in strength (Pearson's coefficient 0.24 to 0.60, p<0.01 for all). All correlations between the dry eye questionnaires and tear film measures were weak (Pearson's coefficient -0.10 to 0.18) and most were not significant. Multivariable linear regression analyses revealed that PTSD and non-ocular pain more closely associated with dry eye symptoms than did tear film parameters. Specifically, non-ocular pain and PTSD accounted for approximately 36% of the variability in DEQ5 scores (R=0.60) and approximately 40% of variability in OSDI scores (R=0.64). Of note, none of the tear parameters remained significantly associated with dry eye symptoms in either model. Dry eye symptoms more closely align to non-ocular pain, depression and PTSD than to tear film parameters. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Profile of ocular trauma in industries-related hospital.

PubMed

Shashikala, P; Sadiqulla, Mohammed; Shivakumar, D; Prakash, K H

2013-05-01

Ocular trauma is a worldwide cause of visual morbidity, a significant proportion of which occurs in the industrial workplace and includes a spectrum of simple ocular surface foreign bodies, abrasions to devastating perforating injuries causing blindness. Being preventable is of social and medical concern. A prospective case series study, to know the profile of ocular trauma at a hospital caters exclusively to factory employees and their families, to co-relate their demographic and clinical profile and to identify the risk factors. Patients with ocular trauma who presented at ESIC Model hospital, Rajajinagar, Bangalore, from June 2010 to May 2011 were taken a detailed demographic data, nature and cause of injury, time interval between the time of injury and presentation along with any treatment received. Ocular evaluation including visual acuity, anterior and posterior segment findings, intra-ocular pressure and gonio-scopy in closed globe injuries, X-rays for intraocular foreign body, B-scan and CT scan were done. Data analyzed as per the ocular trauma classification group. The rehabilitation undertaken medically or surgically was analyzed. At follow-up, the final best corrected visual acuity was noted. A total of 306 cases of ocular trauma were reported; predominantly in 20-40 year age group (72.2%) and in men (75%). The work place related cases were 50.7%and of these, fall of foreign bodies led the list. Visual prognosis was poorer in road traffic accidents rather than work place injuries owing to higher occurrence of open globe injuries and optic neuropathy. Finally, 11% of injured cases ended up with poor vision. Targeting groups most at risk, providing effective eye protection, and developing workplace safety cultures may together reduce occupational eye injuries.

Colored corn starch dust explosion-related ocular injuries at a Taiwan water park: A preliminary report from a single medical center

PubMed Central

Liao, Yi-Lin; Yeh, Lung-Kun; Tsai, Yueh-Ju; Chen, Shin-Yi

2016-01-01

Purpose: To elucidate the manifestations of ocular injuries in the colored corn starch dust explosion at a Taiwan water park. Methods: This is a retrospective, non-comparative, consecutive-interventional case series. Fifty explosion-injury patients on 27 June 2015 treated at Chang-Gung Memorial Hospital, Linkou, were included. Thorough ophthalmic examinations were based on emergent triage and consecutive ophthalmological consultations. Multiple ocular and systemic parameters were assessed. Results: Of the 100 eyes in the 50 cases reviewed, 22 cases were male and 28 cases were female. The mean age was 22.08 ± 4.64 years, and the mean burn total body surface area (TBSA) of patients was 45.92 ± 20.30%. Of the 50 patients, 20 had Grade 1 ocular burns, and the others were without ocular involvement. Two of the 20 cases that presented Grade 1 ocular burns died within 1 month due to other systemic complications. The most common ocular manifestations among those with ocular injuries included periocular swelling (75%), followed by conjunctival chemosis (65%), conjunctival hyperemia (50%), singed eyelashes (20%), cornea epithelial defects (10%), and punctate keratopathy (5%). It is worth mentioning that one patient developed herpes simplex keratitis due to stress 3 weeks after being burned. Half of the 50 patients had facial burns. Specifically, the patients with a greater TBSA presented more significant ocular-burn manifestations than those patients with lower TBSA. Conclusion: Prompt ophthalmologic consultations are particularly necessary for mass burn-casualty patients with facial burns, inhalation injuries, and greater TBSA. The inspection and control of all ignition sources and the manipulation of dust with low concentrations and in an open space are crucial factors to prevent future dust explosions. PMID:29018726

The Effect of Ambient Titanium Dioxide Microparticle Exposure to the Ocular Surface on the Expression of Inflammatory Cytokines in the Eye and Cervical Lymph Nodes.

PubMed

Eom, Youngsub; Song, Jong Suk; Lee, Hyun Kyu; Kang, Boram; Kim, Hyeon Chang; Lee, Hyung Keun; Kim, Hyo Myung

2016-12-01

To investigate the ocular immune response following exposure to airborne titanium dioxide (TiO2) microparticles. Rats in the TiO2-exposed group (n = 10) were exposed to TiO2 particles for 2 hours twice daily for 5 days, while the controls (n = 10) were not. Corneal staining score and tear lactic dehydrogenase (LDH) activity were measured to evaluate ocular surface damage, serum immunoglobulin (Ig) G and E were assayed by using enzyme-linked immunosorbent assay, and the size of cervical lymph nodes was measured. In addition, the expression of interleukin (IL)-4, IL-17, and interferon (IFN)-γ in the anterior segment of the eyeball and cervical lymph nodes was measured by immunohistochemistry, real-time reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analysis. Median corneal staining score (3.0), tear LDH activity (0.24 optical density [OD]), and cervical lymph node size (36.9 mm2) were significantly higher in the TiO2-exposed group than in the control group (1.0, 0.13 OD, and 26.7 mm2, respectively). Serum IgG and IgE levels were found to be significantly elevated in the TiO2-exposed group (P = 0.021 and P = 0.021, respectively). Interleukin 4 expression was increased in the anterior segment of the eyeball and lymph nodes following TiO2 exposure, as measured by immunostaining, real-time RT-PCR, and Western blot. In addition, IL-17 and IFN-γ levels were also increased following TiO2 exposure compared to controls as measured by immunostaining. Exposure to airborne TiO2 induced ocular surface damage. The Type 2 helper T-cell pathway seems to play a dominant role in the ocular immune response following airborne TiO2 exposure.

Photodynamic Therapy (PDT) using intratumoral injection of the 5- aminolevulinic acid (5-ALA) for the treatment of eye cancer in cattle

NASA Astrophysics Data System (ADS)

Hage, Raduan; Mancilha, Geraldo; Zângaro, Renato A.; Munin, Egberto; Plapler, Hélio

2007-02-01

A six-year old Holstein cow with an eye cancer (ocular squamous cell carcinoma) involving the third eyelid and conjunctiva was submitted to photodynamic therapy using intratumoral 20% aminolevulinic acid (5-ALA - Aldrich Chemical Company, Milwaukee, USA) and a light emitting diode (LED - VET LED - MMOptics (R)) with wavelength between 600 and 700 nm, 2 cm diameter circular light beam, power of 150 mW, light dose of 50 J/cm2 as a source of irradiation. Fifteen days after the experimental procedure we observed about 50% tumor reduction and complete remission after 3 months. Relapse was not observed up to 12 months after the treatment. Although the study only includes one animal not allowing definite conclusions, it indicates that PDT represents a safe and technically feasible approach in the treatment of eye cancer in cattle.

Goblet Cells of the Conjunctiva: A Review of Recent Findings

PubMed Central

Gipson, Ilene K

2016-01-01

Goblet cells within the conjunctival epithelium are specialized cells that secrete mucins onto the surface of the eye. Recent research has demonstrated new characteristics of the cells, including factors influencing their differentiation, their gene products and their functions at the ocular surface. The following review summarizes the newly discovered aspects of the role of Spdef, a member of the Ets transcription factor family in conjunctival goblet cell differentiation, the newly discovered goblet cell products including claudin2, the Wnt inhibitor Frzb, and the transmembrane mucin Muc16. The current concepts of conjunctival goblet cell function, including debris removal and immune surveillance are reviewed, as are changes in the goblet cell population in ocular surface diseases. Major remaining questions regarding conjunctival cell biology are discussed. PMID:27091323

Acute sensitivity of the oral mucosa to oncogenic K-ras

PubMed Central

van der Weyden, Louise; Alcolea, Maria P; Jones, Philip H; Rust, Alistair G; Arends, Mark J; Adams, David J

2011-01-01

Mouse models of cancer represent powerful tools for analysing the role of genetic alterations in carcinogenesis. Using a mouse model that allows tamoxifen-inducible somatic activation (by Cre-mediated recombination) of oncogenic K-rasG12D in a wide range of tissues, we observed hyperplasia of squamous epithelium located in moist or frequently abraded mucosa, with the most dramatic effects in the oral mucosa. This epithelium showed a sequence of squamous hyperplasia followed by squamous papilloma with dysplasia, in which some areas progressed to early invasive squamous cell carcinoma, within 14 days of widespread oncogenic K-ras activation. The marked proliferative response of the oral mucosa to K-rasG12D was most evident in the basal layers of the squamous epithelium of the outer lip with hair follicles and wet mucosal surface, with these cells staining positively for pAKT and cyclin D1, showing Ras/AKT pathway activation and increased proliferation with Ki-67 and EdU positivity. The stromal cells also showed gene activation by recombination and immunopositivity for pERK indicating K-Ras/ERK pathway activation, but without Ki-67 positivity or increase in stromal proliferation. The oral neoplasms showed changes in the expression pattern of cytokeratins (CK6 and CK13), similar to those observed in human oral tumours. Sporadic activation of the K-rasG12D allele (due to background spontaneous recombination in occasional cells) resulted in the development of benign oral squamous papillomas only showing a mild degree of dysplasia with no invasion. In summary, we show that oral mucosa is acutely sensitive to oncogenic K-ras, as widespread expression of activated K-ras in the murine oral mucosal squamous epithelium and underlying stroma can drive the oral squamous papilloma–carcinoma sequence. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:21381032

A review of scoring systems for ocular involvement in chronic cutaneous bullous diseases.

PubMed

Lee, Brendon W H; Tan, Jeremy C K; Radjenovic, Melissa; Coroneo, Minas T; Murrell, Dedee F

2018-05-22

Epidermolysis bullosa (EB) and autoimmune blistering diseases (AIBD) describe a group of rare chronic dermatoses characterized by cutaneous fragility and blistering. Although uncommon, significant ocular surface disease (OSD) may occur in both and require ophthalmological assessment. Disease scoring systems have a critical role in providing objective and accurate assessment of disease severity. The objectives of this report were, firstly, to document the prevalence and severity of ocular involvement in EB/AIBD. Secondly, to review and evaluate existing ocular and systemic scoring systems for EB/AIBD. Finally, to identify areas where further development of ocular specific tools in EB/AIBD could be pursued. A literature search was performed in October 2017 utilising Medline, Embase, and Scopus databases. The results were restricted by date of publication, between 01.01.1950 and 31.10.2017. The reference lists of these articles were then reviewed for additional relevant publications. Articles of all languages were included if an English translation was available. Articles were excluded if they were duplicates, had no reference to ocular involvement in EB/AIBD or described ocular involvement in other diseases. Descriptions of ocular involvement in EB/AIBD were identified in 88 peer-reviewed journal articles. Findings reported include but are not limited to: cicatrising conjunctivitis, meibomian gland dysfunction, dry eye disease, trichiasis, symblepharon, fornix fibrosis, keratopathy, ectropion/entropion, ankyloblepharon, corneal ulceration, visual impairment and blindness. Although scoring systems exist for assessment of OSD in mucous membrane pemphigoid, no such tools exist for the other AIBD subtypes or for EB. Several systemic scoring systems exist in the dermatological literature that are efficacious in grading overall EB/AIBD severity, but have limited inclusion of ocular features. To the best of our knowledge, there is no recognised or validated scoring systems which comprehensively stages or grades the spectrum of ocular manifestations in EB/AIBD. There are a range of ocular complications documented in EB and AIBD. Development of a comprehensive ocular scoring system for EB/AIBD which incorporates the delineation between 'activity' and 'damage' would facilitate more objective patient assessment, improved longitudinal monitoring, comparison of intervention outcomes, and provide commonality for discussion of these patients due to the multidisciplinary nature of their care.

The value of high-resolution anoscopy in the diagnosis of anal cancer precursor lesions in HIV-positive patients.

PubMed

Gimenez, Felicidad; Costa-e-Silva, Ivan Tramujas da; Daumas, Adriana; Araújo, José de; Medeiros, Sara Grigna; Ferreira, Luiz

2011-01-01

Anal cancer, although a still rare disease, is being observed in ascending rates among some population segments known to be at risk for the development of the disease. Human papillomavirus (HPV) infection, immunodepression and anal intercourse are some factors associated with the development of the malignancy. Its similarities to cervical cancer have led to many studies aiming to establish guidelines for detecting and treating precursor lesions of anal cancer, with the goal of prevention. High-resolution anoscopy is routinely used for the diagnosis of anal cancer precursor lesions in many centers but the medical literature is still deficient concerning the role of this diagnostic modality. To evaluate diagnostic validation and precision measures of high-resolution anoscopy in comparison to histopathological results of anal biopsies performed in HIV-positive patients treated at the Tropical Medicine Foundation of Amazonas, AM, Brazil. To observe any possible association between some risk factors for the development of anal cancer and the presence of anal squamous intraepithelial lesions. A hundred and twenty-eight HIV-positive patients were submitted to anal canal cytological sampling for the detection of HPV infection by a PCR based method. High-resolution anoscopy was then performed after topical application of acetic acid 3% in the anal canal for 2 minutes. Eventual acetowhite lesions that were detected were recorded in respect to location, and classified by their tinctorial pattern, distribution aspect, relief, surface and vascular pattern. Biopsies of acetowhite lesions were performed under local anesthesia and the specimens sent to histopathological analysis. The patients were interviewed for the presence of anal cancer risk factors. The prevalences of anal HPV infection and of anal squamous intraepithelial lesions in the studied population were, respectively, 79% and 39.1%. High-resolution anoscopy showed sensibility of 90%, specificity of 19.23%, positive predictive value of 41.67%, negative predictive value of 75%, and a kappa coefficient of 0.076. From the analyzed lesions, high-grade squamous intraepithelial lesions was more frequently observed in association to dense (68%), flat (61%), smooth (61%), non-papillary (83%) and normal vascular pattern (70%) acetowhite lesions, while low-grade squamous intraepithelial lesions tended to be associated to dense (66%), flat-raised or raised (68%), granular (59%), non-papillary (62%) and normal vascular pattern (53%) acetowhite lesions. No statistical significance was observed as to the association of epidemiological characteristics and of most of the investigated anal cancer risk factors and presence of acetowhite lesions or anal squamous intraepithelial lesions. However, anal receptive sex and anal HPV infection were significantly associated to anal squamous intraepithelial lesions (P = 0.0493 and P = 0.006, respectively). High-resolution anoscopy demonstrated to be a sensitive, but not specific test for the detection of anal squamous intraepithelial lesions. Risk factors anal receptive sex and anal HPV infection were significantly associated to the presence of anal squamous intraepithelial lesions. Based on high-resolution anoscopy image data, acetowhite lesions relief and surface pattern were prone to distinguish between low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions.

Frequency and risk factors associated with dry eye in patients attending a tertiary care ophthalmology center in Mexico City.

PubMed

Martinez, Jaime D; Galor, Anat; Ramos-Betancourt, Nallely; Lisker-Cervantes, Andrés; Beltrán, Francisco; Ozorno-Zárate, Jorge; Sánchez-Huerta, Valeria; Torres-Vera, Marco-Antonio; Hernández-Quintela, Everardo

2016-01-01

The purpose of this study was to ascertain the frequency and risk factors of dry eye (DE) among patients attending a tertiary care ophthalmology center in Mexico. Approximately 338 consecutive new patients attending a tertiary care ophthalmology center in Mexico City underwent an ocular surface examination, which included tear film break-up time, fluorescein corneal staining, Schirmer's test, and evaluation of meibum quality. Symptoms of DE were evaluated by the Ocular Surface Disease Index and Dry Eye Questionnaire-5. Information on demographics, exposures, past medical and ocular history, and medications was also collected. The frequency of severe DE symptoms was found to be 43% based on the Ocular Surface Disease Index and 30% based on Dry Eye Questionnaire-5. Risk factors significantly associated with increased DE symptoms included dry mouth and gastrointestinal ulcer medications. With regard to signs, aqueous tear deficiency was a less-frequent finding (22%) in our population than evaporative deficiency (94%). Risk factors associated with aqueous tear deficiency were dry mouth and diuretic use. No risk factors were associated with evaporative deficiency. Risk factors associated with meibomian gland dysfunction included old age, male sex, arthritis, and use of an antihypertensive. The only risk factor associated with corneal staining was dry mouth. This is the first study to demonstrate the frequency of symptomatic and clinical DE in a tertiary care ophthalmology center in Mexico. The frequency of DE ranged from 30% using a symptomatic definition to 94% using objective measures. Different risk factors were found for different aspects of DE, suggesting differing underlying pathophysiologies behind different DE subtypes.

A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

PubMed Central

Yang, Qian; Zhang, Yafang; Liu, Xiuping; Wang, Nan; Song, Zhenyu; Wu, Kaili

2017-01-01

Models of benzalkonium chloride (BAC)-induced ocular disruption have been created and are widely used in various animals. This study aimed to compare the effects of BAC on the ocular surfaces of C57BL/6 and BALB/c mice. C57BL/6 and BALB/c mice were treated separately with BAC eye-drops at different concentrations. Eyes were evaluated by scoring epithelial disruption, corneal opacity and neovascularization in vivo, and by histological assays with hematoxylin/eosin (H/E) and periodic acid-Schiff stainings and by determining the expression of inflammatory factors in vitro on Days 7 and 14. The in vivo corneal epithelial disruption, corneal edema/opacity and neovascularization, which were in accordance with the results of the H/E staining and peaked at Day 7, were observed in a dose-dependent manner in the BAC-treated mice, with more severe signs in the C57BL/6 mice than the BALB/c mice. The loss of conjunctival goblet cells in the conjunctivas and the increasing expression of monocyte chemoattractant protein 1 (MCP-1), growth-regulated protein alpha (GROa) and macrophage inflammatory protein-1 alpha (MIP-1a) in the corneas were found in a dose-dependent manner in both strains of mice. Topical application of BAC can dramatically disrupt the ocular surfaces of C57BL/6 and BALB/c mice, and the disruptions were much more severe in the C57BL/6 mice that received high doses of BAC. PMID:28245636

Current concepts of ocular adnexal surgery

PubMed Central

Borrelli, Maria; Geerling, Gerd

2013-01-01

Ophthalmic Plastic and Reconstructive Surgery is a specialized area of ophthalmology that deals with the management of deformities and abnormalities of the eyelids, lacrimal system and the orbit. An ophthalmoplastic surgeon is able to identify and correct abnormalities of the ocular adnexae such as ectropion, lid retraction, conjunctival scarring with severe entropion, that can cause secondary ocular surface disorders; manage patients with watering eye, and when needed intervene with a dacryocystorhinostomy by external or endonasal approach and moreover minimize disfigurement following enucleation or evisceration and prevent further corneal damage, alleviate complains of tearing and grittiness, but also cosmetic complaints in patients with Graves’ orbitopathy. Aim of this manuscript was to review current established and recently evolving surgical procedures. PMID:26504698

Glycerogelatin-based ocular inserts of aceclofenac: physicochemical, drug release studies and efficacy against prostaglandin E₂-induced ocular inflammation.

PubMed

Mathurm, Manish; Gilhotra, Ritu Mehra

2011-01-01

An attempt has been made in the present study to formulate soluble ocular inserts of aceclofenac to facilitate the bioavailability of the drug into the eye, as no eye drop solution could be formulated. Glycero-gelatin ocular inserts/films were prepared and physicochemical parameters and drug release profiles of glycerol-gelatin films of aceclofenac were compared with surface cross-linked films of similar compositions. Ocular irritation of the developed formulation was also checked by HET-CAM test and efficacy of the developed formulation against prostaglandin-induced ocular inflammation in rabbit eye was determined. The non-cross-linked films showed poor mechanical, physicochemical properties, and very little potential of sustaining drug release, however cross-linking the films enhanced tensile strength by 70%, but elasticity decreased by 95%. The cross-linked ocular inserts showed less swelling than non-cross-linked. Formulation AF8 (20% gelatin and 70% glycerin, treated by cross-linker for 1 h) demonstrated the longest drug release for 24 h. As per the kinetic models all films showed a constant drug release with Higuchi diffusion mechanism. Formulation was found to be practically non-irritant. The optimized formulation was tested and compared with eye drops of aceclofenac for anti-inflammatory activity in rabbits against PGE₂-induced inflammation. In vivo studies with developed formulation indicated a significant inhibition of PGE₂-induced PMN migration as compared to eye drops. In conclusion, ocular inserts of aceclofenac was found promising as it achieved sustained drug release and better pharmacodynamic activity.

The natural history of Stevens–Johnson syndrome: patterns of chronic ocular disease and the role of systemic immunosuppressive therapy

PubMed Central

De Rojas, M Victoria; Dart, John K G; Saw, Valerie P J

2007-01-01

Objective To characterize patterns of chronic ocular disease in patients with Stevens–Johnson syndrome (SJS) and its variant toxic epidermal necrolysis (TEN), and to describe their response to treatment. Methods Retrospective case series. A review of hospital records of 30 patients (60 eyes) with ocular manifestations of SJS or TEN was carried out. The principal outcome measure was to identify and classify the patterns of chronic ocular disease in SJS and TEN. The secondary outcome measure was the response to treatment. Results Patterns of chronic ocular disease observed after the acute episode included: mild/moderate SJS, severe SJS, ocular surface failure (SJS‐OSF), recurrent episodic inflammation (SJS‐RI), scleritis (SJS‐S) and progressive conjunctival cicatrisation resembling mucous membrane pemphigoid (SJS‐MMP). The median follow‐up was 5 years (range 0–29). 19 patients (29 eyes (48%)) developed SJS‐OSF, SJS‐RI, SJS‐S or SJS‐MMP during follow‐up. SJS‐OSF was present in 12 patients (18 eyes (30%)). In 5 patients (eight eyes) this developed 1 year after the acute illness, without any further inflammatory episodes; it was associated with SJS‐RI in 1 patient (2 eyes), with SJS‐RI and SJS‐S in 1 patient (1 eye), with SJS‐S in 1 patient (1 eye) and with SJS‐MMP in 4 patients (6 eyes). Episodes of SJS‐RI occurred in 4 patients (7 eyes (12%)). The median time from acute disease to the first episode of SJS‐RI was 8.5 years (range 5–63). SJS‐S developed in 2 patients (4 eyes (7%)), of which 2 eyes subsequently developed SJS‐OSF. SJS‐MMP developed in 5 patients (10 eyes (16.6%)). The median duration from the acute stage to the diagnosis of SJS‐MMP was 2 years (range 1–14). Immunosuppressive therapy successfully controlled inflammation in 10/10 patients with SJS‐MMP, SJS‐RI or SJS‐S. Conclusion Ocular disease in SJS/TEN is not limited solely to the sequelae of the acute phase illness. Patients and physicians need to know that ocular disease progression, due to surface failure and/or acute inflammatory conditions, may occur at variable periods following the acute disease episode. Recognition of this, and prompt access to specialist services, may optimise management of these uncommon patterns of disease in SJS. PMID:17314145

Long-term effect of surface light scattering and glistenings of intraocular lenses on visual function.

PubMed

Hayashi, Ken; Hirata, Akira; Yoshida, Motoaki; Yoshimura, Koichi; Hayashi, Hideyuki

2012-08-01

To investigate the long-term effect of surface light scattering and glistenings of various intraocular lenses (IOLs) on visual function and optical aberrations after cataract surgery. Case-control study. Thirty-five eyes that underwent implantation of a hydrophobic acrylic, silicone, or polymethyl methacrylate (PMMA) IOL more than 10 years ago were recruited. The scattering light intensity of the surface and internal matrix of the optic was measured using Scheimpflug photography. Visual acuity (VA) was measured using VA charts, and contrast VA and that with glare (glare VA) were examined using a contrast sensitivity tester. Ocular higher-order aberrations (HOAs) were measured using a Hartmann-Shack aberrometer. Mean scattering light intensity of the surface and internal matrix of the optic was significantly higher in the acrylic group than in the silicone and PMMA groups (P < .0001). Mean uncorrected VA, photopic and mesopic contrast VA and glare VA, and HOAs did not differ significantly among groups, although mean corrected VA in the acrylic group was significantly better than that in the other groups (P = .0023). Scattering light intensity of the surface and internal matrix did not correlate with VA, contrast VA, or glare VA, and did not correlate with ocular and internal optic HOAs in the acrylic group. At more than 10 years postoperatively, visual function, including contrast sensitivity, and ocular HOAs were comparable among eyes that received acrylic, silicone, and PMMA IOLs. Surface scattering and glistenings with the acrylic IOLs were not significantly correlated with visual function and optical aberrations. Copyright © 2012 Elsevier Inc. All rights reserved.

Nanostructured lipid carriers as novel ophthalmic delivery system for mangiferin: improving in vivo ocular bioavailability.

PubMed

Liu, Rui; Liu, Zhidong; Zhang, Chengui; Zhang, Boli

2012-10-01

The aim of this study was to develop a novel nanostructured lipid carriers (NLCs) system to improve ocular bioavailability of mangiferin (MGN) for the potential treatment of cataract. The physicochemical properties of MGN-loaded NLC (MGN-NLC) formulation were characterized by particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, morphological property, and crystalline state. in vitro characteristics were investigated by drug release from NLC system, physical stability, and corneal permeation through excised rabbit cornea. Moreover, in vivo ocular tolerability was assessed by a modified Draize test and histological microscopy. Preocular retention capability was evaluated by slit-lamp observation. Pharmacokinetic study in the aqueous humor was performed by microdialysis technique. Transmission electron microscopy depicted spherical and uniform morphology. Differential scanning calorimetry and X-ray diffractometry displayed imperfect crystalline lattice. The optimized MGN-NLC formulation exhibited a sustained drug release with 3 months stability and 4.31-fold increase of in vitro corneal permeation. Furthermore, in vivo studies exhibited a high tolerance in the ocular tissues and prolonged drug retention capacity on the corneal surface. Finally, pharmacokinetic study suggested a 5.69-fold increase of ocular bioavailability compared with MGN solution (MGN-SOL). Therefore, NLC system is a promising approach for ocular delivery of MGN. Copyright © 2012 Wiley Periodicals, Inc.

Microscopic and spectroscopic evaluation of novel PLGA-chitosan Nanoplexes as an ocular delivery system.

PubMed

Jain, Gaurav K; Pathan, Shadab A; Akhter, Sohail; Jayabalan, Nirmal; Talegaonkar, Sushma; Khar, Roop K; Ahmad, Farhan J

2011-02-01

The interaction of PLGA-chitosan Nanoplexes with ocular mucosa was investigated ex vivo and in vivo to assess their potential as ocular delivery system. Fluorescent Rhodamine Nanoplexes (Rd-Nanoplexes) were prepared by ionotropic gelation method. The size and morphology of Nanoplexes was investigated by TEM, SEM and PCS. The corneal retention, uptake and penetration of Nanoplexes were analyzed by spectrofluorimetry and confocal microscopy. Corneas from Rd-Nanoplexes-treated rabbits were evaluated for the in vivo uptake and ocular tolerance. The Nanoplexes prepared were round with a mean diameter of 115.6±17nm and the encapsulation efficiency of Rd was 59.4±2.5%. Data from ex vivo and in vivo studies showed that the amounts of Rd in the cornea were significantly higher for Nanoplexes than for a control Rd solution, these amounts being fairly constant for up to 24h. Confocal microscopy of the corneas revealed paracellular and transcellular uptake of the Nanoplexes. The uptake mechanism postulated was adsorptive-mediated endocytosis and opening of the tight junctions between epithelial cells. No alteration was microscopically observed after ocular surface exposure to Nanoplexes. Taken together, these data demonstrate that Nanoplexes are potentially useful as ocular drug carriers. Copyright © 2010 Elsevier B.V. All rights reserved.

OCT-based profiler for automating ocular surface prosthetic fitting (Conference Presentation)

NASA Astrophysics Data System (ADS)

Mujat, Mircea; Patel, Ankit H.; Maguluri, Gopi N.; Iftimia, Nicusor V.; Patel, Chirag; Agranat, Josh; Tomashevskaya, Olga; Bonte, Eugene; Ferguson, R. Daniel

2016-03-01

The use of a Prosthetic Replacement of the Ocular Surface Environment (PROSE) device is a revolutionary treatment for military patients that have lost their eyelids due to 3rd degree facial burns and for civilians who suffer from a host of corneal diseases. However, custom manual fitting is often a protracted painful, inexact process that requires multiple fitting sessions. Training for new practitioners is a long process. Automated methods to measure the complete corneal and scleral topology would provide a valuable tool for both clinicians and PROSE device manufacturers and would help streamline the fitting process. PSI has developed an ocular anterior-segment profiler based on Optical Coherence Tomography (OCT), which provides a 3D measure of the surface of the sclera and cornea. This device will provide topography data that will be used to expedite and improve the fabrication process for PROSE devices. OCT has been used to image portions of the cornea and sclera and to measure surface topology for smaller contact lenses [1-3]. However, current state-of-the-art anterior eye OCT systems can only scan about 16 mm of the eye's anterior surface, which is not sufficient for covering the sclera around the cornea. In addition, there is no systematic method for scanning and aligning/stitching the full scleral/corneal surface and commercial segmentation software is not optimized for the PROSE application. Although preliminary, our results demonstrate the capability of PSI's approach to generate accurate surface plots over relatively large areas of the eye, which is not currently possible with any other existing platform. Testing the technology on human volunteers is currently underway at Boston Foundation for Sight.

Prevalence of dry eye syndrome after allogeneic hematopoietic stem cell transplantation.

PubMed

Ivanir, Yair; Shimoni, Avichai; Ezra-Nimni, Orit; Barequet, Irina S

2013-05-01

To evaluate the prevalence, severity, and effect of dry eye in patients after allogeneic hematopoietic stem cell transplantation (aHSCT) and to correlate the findings to the duration after transplantation. A total of 222 eyes of 111 patients after aHSCT at the Department of Bone Marrow Transplantation, Sheba Medical Center, Israel in a consecutive 3-year period. All patients underwent a full ophthalmic examination and filled the ocular surface disease index (OSDI) questionnaire to assess ocular involvement in the form of dry eye syndrome or any other ocular manifestation. The main outcome measures were best-corrected visual acuity, tear break-up time, corneal fluorescein staining, Schirmer test, and OSDI questionnaire. A total of 111 patients were recruited. In 37%, a diagnosis of ocular graft versus host disease was previously made and 46% had no previous ocular examination. Schirmer test was less than 5 mm in 50% of all patients, and in 30% of patients with undiagnosed ocular involvement. The mean OSDI score was 13, and in 28% it was above 20. Correlation was found between visual acuity decrease and high OSDI score to the diagnosis of ocular graft versus host disease and signs of dry eye syndrome. A trend of worsening dry eye was observed up to the second half of the second year posttransplantation. Although many patients are either asymptomatic or do not seek ophthalmic examination, severe dry eye is a common finding after aHSCT. Mandatory follow-up, patient education, and early treatment may improve the quality of life.

[Preservatives in ophthalmology].

PubMed

Messmer, E M

2012-11-01

Preservatives are a legal requirement for eye drops in multidose containers. Moreover, they are necessary for stabilization and intraocular penetration for a number of ophthalmic preparations. Most preservatives act in a relatively unspecific manner as detergents or by oxidative mechanisms and thereby cause side effects at the ocular surface. They may also affect the lens, trabecular meshwork and the retina. Benzalkonium chloride is the most commonly used preservative in ophthalmology and is more toxic than other or newer preservatives, such as polyquaternium-1 (Polyquad), sodium perborate, oxychloro-complex (Purite®) and SofZia. Preservative-free topical medication is highly recommended for patients with ocular surface disease, frequent eye drop administration, proven allergy to preservatives and contact lens wear.

Computed tear film and osmolarity dynamics on an eye-shaped domain

PubMed Central

Li, Longfei; Braun, Richard J.; Driscoll, Tobin A.; Henshaw, William D.; Banks, Jeffrey W.; King-Smith, P. Ewen

2016-01-01

The concentration of ions, or osmolarity, in the tear film is a key variable in understanding dry eye symptoms and disease. In this manuscript, we derive a mathematical model that couples osmolarity (treated as a single solute) and fluid dynamics within the tear film on a 2D eye-shaped domain. The model includes the physical effects of evaporation, surface tension, viscosity, ocular surface wettability, osmolarity, osmosis and tear fluid supply and drainage. The governing system of coupled non-linear partial differential equations is solved using the Overture computational framework, together with a hybrid time-stepping scheme, using a variable step backward differentiation formula and a Runge–Kutta–Chebyshev method that were added to the framework. The results of our numerical simulations provide new insight into the osmolarity distribution over the ocular surface during the interblink. PMID:25883248

Ocular injury with high-pressure paint: a case report.

PubMed

Bandyopadhyay, Chitrabhanu; Mitra, Arjit; Harrison, Rosalind J

2009-01-01

Chemical injury to the eye is an ophthalmic emergency that can be caused by a work-related accident or common household products. Uradil SZ261 G3Z-65 is a resin containing butyl gycol (2-butoxyethanol) and ethyl ethanol amine (2-dimethyaminoethanol). It is used in stoving enamels for interior and exterior use. The authors report a case of ocular surface injury with a highpressure industrial spray paint-Waterborne Stoving Gentian Blue containing Uradil.

Safety parameters for avoiding acute ocular damage from the reflected CO2 (10.6 microns) laser beam.

PubMed

Friedman, N R; Saleeby, E R; Rubin, M G; Sandu, T; Krull, E A

1987-11-01

Reflections from instruments in the surgical field involving the CO2 laser beam present a serious ocular hazard. In addition to the use of plastic or glass protective eyewear, this hazard can be minimized by utilizing anodized instruments and recognizing the specific distances at which various reflections are no longer hazardous depending upon certain variables, including laser output wattage, emergent beam lengths, and surface characteristics of the reflecting instruments.

[Light protection for xeroderma pigmentosum].

PubMed

Ettinger, M; Berneburg, M

2017-05-01

Xeroderma pigmentosum is a rare autosomal recessive disorder which is caused by germinal mutations responsible for the repair of ultraviolet (UV) radiation-induced DNA lesions. It is characterized by hypersensitivity to UV radiation, poikiloderma, ocular surface disease, and in some patients pronounced sunburn and neurological disease. Patients have a very high risk of developing ocular and skin cancer on exposed body sites. No cure is available for these patients except complete protection from all types of UV radiation.

HPV- and non-HPV-related subtypes of penile squamous cell carcinoma (SCC): Morphological features and differential diagnosis according to the new WHO classification (2015).

PubMed

Sanchez, Diego F; Cañete, Sofía; Fernández-Nestosa, María José; Lezcano, Cecilia; Rodríguez, Ingrid; Barreto, José; Alvarado-Cabrero, Isabel; Cubilla, Antonio L

2015-05-01

The majority of penile carcinomas are squamous cell carcinomas originating in the squamous mucosa covering the glans, coronal sulcus, or inner surface of the foreskin, the 3 latter sites comprising the penile anatomical compartments. There is a variegated spectrum of subtypes of penile squamous cell carcinomas according to recent classification schemes. Currently, because of etiological and prognostic considerations, 2 morphologically and molecularly distinctive groups of subtypes of penile SCCs based on the presence of HPV were delineated. The predominant cell composition of tumors associated with HPV is the basaloid cell, which is the hallmark and best tissue marker for the virus. Tumors negative for the virus, however, are preferentially of lower grade and keratinizing maturing neoplasms with the exception of sarcomatoid carcinoma. HPV is detected in research studies by PCR or in situ hybridization (ISH) technologies, but p16 immunohistochemical stain is an adequate and less-expensive surrogate that is useful in the routine practice of pathology. The aim of this review is to demonstrate the variable morphological phenotypic expression of penile tumors separating non-HPV- and HPV-related neoplasms and to add morphological information that will justify subclassifying squamous cell carcinomas in a number of special subtypes. A brief discussion of the differential diagnosis in each category is also provided. Copyright © 2015 Elsevier Inc. All rights reserved.

Multimodal imaging of ocular surface of dry eye subjects

NASA Astrophysics Data System (ADS)

Zhang, Aizhong; Salahura, Gheorghe; Kottaiyan, Ranjini; Yoon, Geunyoung; Aquavella, James V.; Zavislan, James M.

2016-03-01

To study the relationship between the corneal lipid layer and the ocular surface temperature (OST), we conducted a clinical trial for 20 subjects. Subjects were clinically screened prior to the trial. Of the 20 subjects, 15 have Meibomian gland dysfunction (MGD), and 5 have aqueous-deficient dry eye (ADDE). A custom, circularly polarized illumination video tearscope measured the lipid layer thickness of the ocular tear film. A long-wave infrared video camera recorded the dynamic thermal properties of the ocular team film. The results of these two methods were analyzed and compared. Using principal component analysis (PCA) of the lipid layer distribution, we find that the 20 subjects could be categorized into five statistically significant groups, independent of their original clinical classification: thin (6 subjects), medium (5 subjects), medium and homogenous (3 subjects), thick (4 subjects), and very thick (2 subjects) lipids, respectively. We also conducted PCA of the OST data, and recategorized the subjects into two thermal groups by k-means clustering: one includes all ADDE subjects and some MGD subjects; the other includes the remaining MGD subjects. By comparing these two methods, we find that dry eye subjects with thin (<= 40 nm) lipids have significantly lower OST, and a larger OST drop range, potentially due to more evaporation. However, as long as the lipid layer is not thin (> 40 nm), there is no strong correlation between the lipid layer thickness and heterogeneity and the OST patterns.

Prepare to Care, A Supported Self-Management Intervention for Head and Neck Cancer CaregiversHead and Neck Cancer

ClinicalTrials.gov

2018-04-26

Caregiver; Malignant Head and Neck Neoplasm; Paranasal Sinus Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage I Hypopharyngeal Squamous Cell Carcinoma; Stage I Laryngeal Squamous Cell Carcinoma; Stage I Lip and Oral Cavity Squamous Cell Carcinoma; Stage I Oropharyngeal Squamous Cell Carcinoma; Stage II Hypopharyngeal Squamous Cell Carcinoma; Stage II Laryngeal Squamous Cell Carcinoma; Stage II Lip and Oral Cavity Squamous Cell Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Lip and Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Laryngeal Squamous Cell Carcinoma; Stage IV Lip and Oral Cavity Squamous Cell Carcinoma; Stage IV Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Hypopharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Hypopharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

Hydrocortisone concentration influences time to clinically significant healing of acute inflammation of the ocular surface and adnexa - results from a double-blind randomized controlled trial.

PubMed

Sergiyenko, Nikolay; Sukhina, Ludmila; Bezdetko, Pavel; Kovalenko, Yuriy; Nikitin, Nikolai; Merzbacher, Matthias; Gross, Dorothea; Kohnen, Ralf

2014-05-10

The efficacy of topical ophthalmic corticosteroids depends upon small modifications in preparations, such as drug concentration.The aim of this study was to confirm that hydrocortisone acetate (HC-ac) ophthalmic ointments of 2.5% and 1% are more effective than a 0.5% eye ointment. In this randomized, double-blind, placebo-controlled, parallel-group clinical study, the change of signs and symptoms of acute inflammation of the ocular surface and adnexa was evaluated in 411 subjects. Median time to clinically relevant response as estimated by 50% reduction in clinical signs and symptoms (CSS) total score over the entire trial was similar for subjects treated with HC-ac 2.5% (73.5 h) and for subjects treated with HC-ac 1.0% (67.7 h) and was considerably and significantly longer for subjects treated with HC-ac 0.5% (111.8 h) [p < 0.001 for both dosages]. All trial medications were safe and well tolerated. Hydrocortisone acetate 2.5% and Hydrocortisone acetate 1% eye ointments are efficacious and safe treatments for acute inflammations of the ocular surface or adnexa, and showed significantly better efficacy than a control group treated with Hydrocortisone acetate 0.5% therapy. Current Controlled Trials ISRCTN15464650.

Mechanisms Involved in Injury and Repair of the Murine Lacrimal Gland: Role of Programmed Cell Death and Mesenchymal Stem Cells

PubMed Central

Zoukhri, Driss

2011-01-01

The non-keratinized epithelia of the ocular surface are constantly challenged by environmental insults, such as smoke, dust, and airborne pathogens. Tears are the sole physical protective barrier for the ocular surface. Production of tears in inadequate quantity or of inadequate quality results in constant irritation of the ocular surface, leading to dry eye disease, also referred to as keratoconjunctivitis sicca (KCS). Inflammation of the lacrimal gland, such as occurs in Sjögren’s syndrome, sarcoidosis, chronic graft versus-host disease, and other pathological conditions, results in inadequate secretion of the aqueous layer of the tear film, and is a leading cause of dry eye disease. The hallmarks of lacrimal gland inflammation are the presence of immune cell infiltrates, loss of acinar epithelial cells (the secreting cells), and increased production of proinflammatory cytokines. To date, the mechanisms leading to acinar cell loss and the associated decline in lacrimal gland secretion are still poorly understood. It is also not understood why the remaining lacrimal gland cells are unable to proliferate in order to regenerate a functioning lacrimal gland. This article reviews recent advances in exocrine tissue injury and repair, with emphasis on the roles of programmed cell death and stem/progenitor cells. PMID:20427009

Exploring the Predisposition of the Asian Eye to Development of Dry Eye.

PubMed

Craig, Jennifer P; Wang, Michael T M; Kim, Dabin; Lee, Jung Min

2016-07-01

To investigate the influence of eyelid shape on tear film quality, ocular surface characteristics and dry eye symptomatology by comparing Asian and Caucasian populations. Seventy-four age-matched participants were recruited in a cross-sectional study. Participants were classified into Asian single lid (ASL), Asian double lid (ADL), and Caucasian double lid (CDL) groups. Dry eye symptomatology, ocular surface characteristics, and tear film quality were evaluated in a single clinical session. Meibomian gland dropout was significantly greater in both the ASL and ADL groups than in the CDL group (all P<.05). A greater proportion of ASL and ADL participants exhibited incomplete blinking than CDL patients (all P<.05). There were no significant differences in tear film quality and dry eye symptomatology between the three groups (all P>.05). Exposed ocular surface area, lissamine green staining, and lid wiper epitheliopathy were significantly greater in the ADL group compared to the CDL group (all P<.05). The CDL group displayed significantly greater anterior blepharitis and lid telangiectasia grades compared to both ASL and ADL groups (all P<.05). A higher degree of meibomian gland dropout and incomplete blinking was observed in both Asian groups compared to the Caucasian group, potentially predisposing these groups to dry eye. Copyright © 2016 Elsevier Inc. All rights reserved.

Oral antioxidant therapy for marginal dry eye.

PubMed

Blades, K J; Patel, S; Aidoo, K E

2001-07-01

To assess the efficacy of an orally administered antioxidant dietary supplement for managing marginal dry eye. A prospective, randomised, placebo controlled trial with cross-over. Eye Clinic, Department of Vision Sciences, Glasgow Caledonian University. Forty marginal dry eye sufferers composed of 30 females and 10 males (median age 53 y; range 38-69 y). Baseline assessments were made of tear volume sufficiency (thread test), tear quality (stability), ocular surface status (conjunctival impression cytology) and dry eye symptoms (questionnaire). Each subject was administered courses of active treatment, placebo and no treatment, in random order for 1 month each and results compared to baseline. Tear stability and ocular surface status were significantly improved following active treatment (P<0.05). No changes from baseline were detected following administration of placebo and no treatment (P>0.05). Absolute increase in tear stability correlated with absolute change in goblet cell population density. Tear volume was not improved following any treatment period and dry eye symptom responses were subject to placebo effect. Oral antioxidants improved both tear stability and conjunctival health, although it is not yet understood whether increased ocular surface health mediates increased tear stability or vice versa. This study was supported by a PhD scholarship funded by the Department of Vision Sciences, Glasgow Caledonian University, Scotland. Antioxidant supplements and placebos were kindly donated by Vitabiotics.

4A syndrome: ocular surface investigation in an Italian young patient.

PubMed

Aragona, Pasquale; Rania, Laura; Roszkowska, Anna Maria; Puzzolo, Domenico; Micali, Antonio; Pisani, Antonina; Salzano, Giuseppina; Messina, Maria Francesca

2014-12-08

Allgrove's 4A syndrome determines ocular surface changes. This is the first report providing an up-to-dated analysis of the ocular surface in an affected patient. An 18-years-old male Caucasian patient, with a complex progressive gait disorder and adrenal insufficiency, was referred for ophthalmic evaluation, as part of the clinical assessment. He underwent the following tests: best corrected visual acuity, tear osmolarity, tear film break-up time (BUT), corneal fluorescein staining, Schirmer's I test, lid margin assessment, corneal sensitivity, in vivo corneal confocal microscopy, conjunctival impression cytology, tonometry and fundus exam. A dry eye condition was documented by the Schirmer's I test of 0 mm/5' in both eyes, accompanied by tear hyperosmolarity, mild meibomian gland dysfunction, reduced BUT, mucus filaments in the tear film and conjunctival epithelium metaplasic changes. The corneal confocal microscopy showed the presence of activated keratocytes, while the nerve pattern was normal. The dry eye in this patient appears to be due to tear aqueous deficiency and can be considered as part of the 4A syndrome. The decreased tear production, resulting from a deterioration of the autonomic innervation of the lacrimal glands rather than an impaired corneal innervation, can be considered as part of the systemic autonomic dysfunction present in this disease.

Ocular surface inflammation, and nerve growth factor level in tears in active thyroid-associated ophthalmopathy.

PubMed

Yoon, Jin Sook; Choi, Soo Hyun; Lee, Joon H; Lee, Sung Jun; Lee, Sang Yeul

2010-02-01

To measure tear nerve growth factor (NGF) concentrations in cases of active thyroid-associated ophthalmopathy (TAO) before and after glucocorticoid treatment, and to correlate NGF levels with disease inflammatory activity and thyroid autoantibody concentration. The study involved 20 patients with active TAO and 20 age- and gender-matched controls. Tear break-up time (BUT) was obtained, the Schirmer test was performed, and tear NGF/total protein ratio was measured in control subjects and patients with active TAO before, and 2 and 4 weeks after, steroid treatment. Tear BUT and Schirmer values significantly increased after 2 and 4 weeks of steroid treatment (p < 0.001 and p = 0.004 respectively). Baseline tear NGF/total protein ratio was higher in patients with active TAO than in control subjects, and the ratio significantly decreased after 2 and 4 weeks of steroid treatment (p < 0.001). Tear NGF/total protein ratio did not correlate with inflammatory activity score, exophthalmos value and thyroid binding inhibiting immunoglobulin (TBII) level (p > 0.05). Tear NGF may have a specific role in ocular surface inflammation, which protects against ocular surface damage in patients with active TAO. Anti-inflammatory treatment significantly reduced the level of NGF in tears, increased tear film stability and production, and decreased congestive symptoms.

Modified osteo-odonto keratoprosthesis--the Indian experience--results of the first 50 cases.

PubMed

Iyer, Geetha; Pillai, Vinay S; Srinivasan, Bhaskar; Falcinelli, Giovanni; Padmanabhan, Prema; Guruswami, Sitalakshmi; Falcinelli, Giancarlo

2010-07-01

To study the results of the modified osteo-odonto keratoprosthesis (MOOKP) surgery in bilateral end-stage ocular surface disorders. The MOOKP surgery is performed as a routine in 3 stages. Stage 1A involves removal of the iris and anterior vitrectomy with a corneal transplant if indicated. Stage 1B + 1C usually performed simultaneously involves harvesting the buccal mucosa and transplanting it onto the ocular surface along with fashioning of the osteo-odonto alveolar lamina. Stage 2 involves transplanting the osteo-odonto alveolar lamina to the eye 3 months later. The MOOKP surgery was completed in 50 eyes of 47 patients with a mean follow-up of 15.38 months (range: 1-54 months). Anatomic success was achieved in 96% of the eyes. Functional success of visual acuity > or = 20/60 was noted in 66% of eyes. Complications included oroantral fistula (6%), trophic mucosal alterations (8%), lamina exposure (central 6% and peripheral 8%), mucous membrane overgrowth (2%), hypotony (2%), expulsion of optic cylinder (4%), endophthalmitis (2%), glaucoma (20%), sterile vitritis (6%), and retinal detachment (2%). MOOKP is the keratoprosthesis of choice in bilateral end-stage ocular surface disorders in the Indian subcontinent. Complications do occur and have to be recognized and treated early.

Therapeutic targets in dry eye syndrome.

PubMed

Peral, Assumpta; Domínguez-Godínez, Carmen O; Carracedo, Gonzalo; Pintor, Jesús

2008-04-01

Dry eye is a multifactorial disease of the tears and the ocular surface that manifests with a wide variety of signs and symptoms. It is prevalent in about 33% of the population worldwide. Due to the importance of the pathology, new tests, drugs and technologies have been developed to assist the diagnosis, management and follow-up of the disease. Current available therapies try to alleviate symptoms and to reduce signs in order to restore the ocular surface. Depending on the etiology of the pathology it is possible to use lubricants, secretagogues, biological tear substitutes or antiinflammatory drugs, either independently or combined. Nowadays, the therapies under clinical trial are devoted to stimulating tear components (e.g., diquafosol, a P2Y receptor agonist), or mucin secretion (e.g., rebamipide, an amino acid analogue of quinolinone). Others include gefarnate, a water-insoluble terpene fatty acid that contributes to restoring mucins on the ocular surface, or cevimeline, an oral cholinergic agonist that reduces the symptoms associated with dry eye. Other potential compounds described in patents are in a lower phase of drug development. These compounds come from different families of therapies, and among others, can be found in the form of steroidal and nonsteroidal antiinflammatory agents, vitamins A and D, neurotransmitters and neuropeptides. Copyright 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

Corneal Mechanical Thresholds Negatively Associate With Dry Eye and Ocular Pain Symptoms.

PubMed

Spierer, Oriel; Felix, Elizabeth R; McClellan, Allison L; Parel, Jean Marie; Gonzalez, Alex; Feuer, William J; Sarantopoulos, Constantine D; Levitt, Roy C; Ehrmann, Klaus; Galor, Anat

2016-02-01

To examine associations between corneal mechanical thresholds and metrics of dry eye. This was a cross-sectional study of individuals seen in the Miami Veterans Affairs eye clinic. The evaluation consisted of questionnaires regarding dry eye symptoms and ocular pain, corneal mechanical detection and pain thresholds, and a comprehensive ocular surface examination. The main outcome measures were correlations between corneal thresholds and signs and symptoms of dry eye and ocular pain. A total of 129 subjects participated in the study (mean age 64 ± 10 years). Mechanical detection and pain thresholds on the cornea correlated with age (Spearman's ρ = 0.26, 0.23, respectively; both P < 0.05), implying decreased corneal sensitivity with age. Dry eye symptom severity scores and Neuropathic Pain Symptom Inventory (modified for the eye) scores negatively correlated with corneal detection and pain thresholds (range, r = -0.13 to -0.27, P < 0.05 for values between -0.18 and -0.27), suggesting increased corneal sensitivity in those with more severe ocular complaints. Ocular signs, on the other hand, correlated poorly and nonsignificantly with mechanical detection and pain thresholds on the cornea. A multivariable linear regression model found that both posttraumatic stress disorder (PTSD) score (β = 0.21, SE = 0.03) and corneal pain threshold (β = -0.03, SE = 0.01) were significantly associated with self-reported evoked eye pain (pain to wind, light, temperature) and explained approximately 32% of measurement variability (R = 0.57). Mechanical detection and pain thresholds measured on the cornea are correlated with dry eye symptoms and ocular pain. This suggests hypersensitivity within the corneal somatosensory pathways in patients with greater dry eye and ocular pain complaints.

Corneal Mechanical Thresholds Negatively Associate With Dry Eye and Ocular Pain Symptoms

PubMed Central

Spierer, Oriel; Felix, Elizabeth R.; McClellan, Allison L.; Parel, Jean Marie; Gonzalez, Alex; Feuer, William J.; Sarantopoulos, Constantine D.; Levitt, Roy C.; Ehrmann, Klaus; Galor, Anat

2016-01-01

Purpose To examine associations between corneal mechanical thresholds and metrics of dry eye. Methods This was a cross-sectional study of individuals seen in the Miami Veterans Affairs eye clinic. The evaluation consisted of questionnaires regarding dry eye symptoms and ocular pain, corneal mechanical detection and pain thresholds, and a comprehensive ocular surface examination. The main outcome measures were correlations between corneal thresholds and signs and symptoms of dry eye and ocular pain. Results A total of 129 subjects participated in the study (mean age 64 ± 10 years). Mechanical detection and pain thresholds on the cornea correlated with age (Spearman's ρ = 0.26, 0.23, respectively; both P < 0.05), implying decreased corneal sensitivity with age. Dry eye symptom severity scores and Neuropathic Pain Symptom Inventory (modified for the eye) scores negatively correlated with corneal detection and pain thresholds (range, r = −0.13 to −0.27, P < 0.05 for values between −0.18 and −0.27), suggesting increased corneal sensitivity in those with more severe ocular complaints. Ocular signs, on the other hand, correlated poorly and nonsignificantly with mechanical detection and pain thresholds on the cornea. A multivariable linear regression model found that both posttraumatic stress disorder (PTSD) score (β = 0.21, SE = 0.03) and corneal pain threshold (β = −0.03, SE = 0.01) were significantly associated with self-reported evoked eye pain (pain to wind, light, temperature) and explained approximately 32% of measurement variability (R = 0.57). Conclusions Mechanical detection and pain thresholds measured on the cornea are correlated with dry eye symptoms and ocular pain. This suggests hypersensitivity within the corneal somatosensory pathways in patients with greater dry eye and ocular pain complaints. PMID:26886896

Mucoadhesive microparticles with a nanostructured surface for enhanced bioavailability of glaucoma drug.

PubMed

Park, Chun Gwon; Kim, Young Kook; Kim, Mi Jeung; Park, Min; Kim, Myung Hun; Lee, Seung Ho; Choi, Sung Yoon; Lee, Won Seok; Chung, You Jung; Jung, Young Eun; Park, Ki Ho; Choy, Young Bin

2015-12-28

Topical drug administration to the eye is limited by low drug bioavailability due to its rapid clearance from the preocular surface. Thus, multiple daily administrations are often needed, but patient compliance is low, hence a high chance of unsatisfactory treatment of ocular diseases. To resolve this, we propose mucoadhesive microparticles with a nanostructured surface as potential carriers for delivery of brimonidine, an ocular drug for glaucoma treatment. For sustained drug delivery, the microparticles were composed mainly of a diffusion-wall material, poly(lactic-co-glycolic acid) and a mucoadhesive polymer, polyethylene glycol, was used as an additive. Due to their nanostructured surface, the microparticles with a mucoadhesive material exhibited a 13-fold increase in specific surface area and could thus adhere better to the mucous layer on the eye, as compared with the conventional spherical microparticles. When loaded with brimonidine, the mucoadhesive microparticles with a nanostructured surface increased both drug bioavailability and its activity period by a factor of more than 2 over Alphagan P, a marketed eye drop of brimonidine. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of tear evaporation from ocular surface by functional infrared thermography.

PubMed

Tan, Jen-Hong; Ng, E Y K; Acharya, U Rajendra

2010-11-01

A novel technique was developed to measure tear evaporation and monitor its variation with respect to time, for the studying of ocular physiology based on dynamic functional infrared thermography and the first law of thermodynamics using the measured ocular surface temperatures (OSTs). This is a noninvasive, noncontact temperature measuring method that is widely applied in the field of biomedicine. A simple method based on the ocular thermal data was proposed to measure the rate of tear evaporation. The OST of 60 normal subjects were recorded in the form of sequential thermal images. For each thermal sequence, the ocular region was selected and warped to a standard form. Thermal data within the regions were processed, on the basis of the first law of thermodynamics to derive the evaporation rate. For elder subjects (aged above 35), the rate was determined to be 55.82 Wm(-2) and for younger subjects, the rate was 58.9 Wm(-2). The corneal rate of evaporation in elder subjects was found statistically (p < 0.11) larger than their younger counterparts. The rate of blinking was observed to be related to the variation of evaporation rate. The authors have measured the evaporation rate on a sequence of thermographic images. A region of interest was selected at first and the same region on all the images were warped into a standard form. Calculations were performed based on the thermal data in those regions to obtain the values of interest. The authors found that the tear evaporation rate for subjects of all age groups was 57.36 +/- 12.73 Wm(-2) and the corneal tear evaporation was higher in elder subjects. The corneal rate of evaporation fluctuated in a larger magnitude in subjects who blinked more than average.

Increased numbers of Demodex in contact lens wearers.

PubMed

Jalbert, Isabelle; Rejab, Shazana

2015-06-01

The aim of this study was to determine if Demodex infestation is more frequent in contact lens wearers than in nonwearers. Secondary aims were to evaluate the effects of Demodex on the ocular surface (symptoms and signs) and to evaluate the ability of confocal laser scanning microscopy to detect and quantify the Demodex infestation compared with the conventional light microscopic technique. Forty Asian female participants (20 nonwearers, 20 lens wearers) with a mean (± SD) age of 27 (± 9) years were recruited. Ocular comfort scores (Ocular Surface Disease Index, Ocular Comfort Index, and Dry Eye Questionnaire), vital staining (corneal, conjunctival, and lid wiper), tear osmolarity, tear breakup time, and meibomian gland evaluation were evaluated. Demodex was detected using in vivo confocal microscopy and conventional light microscopy. The number of Demodex was higher in lens wearers than in nonwearers (7.6 [± 5.8] vs. 5.0 [± 3.1]; p = 0.02). Demodex was observed in a large majority (90%) of lens wearers and in 65% of nonwearers using confocal microscopy (p = 0.06). The detection rate was lower in both groups using conventional light microscopy (p = 0.003) where Demodex could only be confirmed in 70% and 60% of lens wearers and nonwearers, respectively. The number of Demodex tended to increase with age (ρ = 0.28, p = 0.08), but Demodex did not appear to affect ocular comfort or any clinical signs (p > 0.05). Contact lens wearers harbor Demodex as frequently as nonwearers and in higher numbers, which is best detected using in vivo confocal microscopy. The significance of these findings is uncertain because no associations were found with any symptoms and signs of dry eye disease.

Immunological impression cytology of the conjunctival epithelium in patients with thyroid orbitopathy-related dry eye.

PubMed

Hsu, S L; Lee, P Y; Chang, C H; Chen, C H

2016-08-30

Thyroid orbitopathy (TO) is an autoimmune disease that is complicated by ocular surface disorders, leading to discomfort. Dry eye is very prevalent in patients with TO. Recent studies on the pathogenesis of dry eye have focused on the inflammatory process, and some supporting evidence has been discovered. Because TO is a disorder of autoimmune origin, we assumed that the association between TO and dry eye is related to inflammation. Inflammation of the ocular surface in TO-related dry eye has not been well studied. In this study, we assessed cellular inflammation of the ocular surface and the cytokine profiles in patients with TO-related dry eye. Conjunctival impression cytology (CIC) was assessed with an immunofluorescent assay. TO-related dry eye was diagnosed by using the Schirmer test, tear break-up time, thyroid function, and clinical signs. CIC was combined with immunological staining of interleukin-1a (IL-1a), IL-1b, and IL- 6. The immunological impression cytology (IC) grade was compared to the clinical activity score of TO. All TO patients with dry eye were positive for IL-1a, IL-1b, and IL-6. However, the normal controls were also positive for IL-1a. A trend was observed between the clinical inflammatory score and immunological IC grade. This study was the first to delineate the immunological IC of TO-related dry eye. Our study aimed to investigate the pathogenesis of dry eye in TO. Our findings suggest that the conjunctival cytokines IL-1a, IL-1b, and IL-6 may play a role. The results of this study will be useful for future studies of additional inflammatory cytokines, and the levels of these cytokines could be used as an outcome to assess the efficacy of treatment, such as anti-cytokine or immunosuppression therapy, in patients with TO-related dry eye or other ocular surface inflammatory disorders.

Effects of silicone hydrogel contact lens wear on ocular surface sensitivity to tactile, pneumatic mechanical, and chemical stimulation.

PubMed

Situ, Ping; Simpson, Trefford L; Jones, Lyndon W; Fonn, Desmond

2010-12-01

To determine the effects of silicone hydrogel lens wear and lens-solution interactions on ocular surface sensitivity. Forty-eight adapted lens wearers completed the study, which comprised two phases. Phase 1 included habitual lens wear, no lens wear (7 ± 3 days), and balafilcon A lenses (PV; PureVision; Bausch & Lomb, Rochester, NY) with a hydrogen peroxide-based regimen for 2 weeks; phase 2 included wear of PV with the use of a multipurpose solution containing either polyhexamethylene-biguanide (PHMB) or Polyquad/Aldox (Alcon Laboratories, Fort Worth, TX) preservative, each for 1 week, with a 2-week washout period between solutions. Tactile and pneumatic (mechanical and chemical) stimuli were delivered, and thresholds were determined by Cochet-Bonnet (Luneau Ophthalmologie, Chartres, France) and Belmonte (Cooperative Research Centre for Eye Research and Technology, Sydney, NSW, Australia) pneumatic esthesiometers, respectively. Corneal and conjunctival thresholds and staining scores were assessed at baseline, after 2 and 8 hours of lens wear on day 1 and at the end of each wearing cycle (2 hours). In phase 1, compared to the no-lens baseline, corneal tactile thresholds increased at the 1-day, 8-hour and the 2-week visits (P < 0.05), whereas conjunctival mechanical thresholds decreased at the 1-day, 2-hour and the 2-week visits (P < 0.05). In phase 2, the chemical thresholds were lower with PHMB-preserved solution compared with the Polyquad/Aldox system at the 1-day, 2-hour and the 1-week visits (P < 0.05). Staining scores correlated inversely with conjunctival chemical thresholds (all P < 0.05). Ocular surface sensitivity changed in adapted lens wearers, when lenses were refit after a no-lens interval and during lens wear with different care regimens. The corneal staining that was observed with certain lens-solution combinations was accompanied by sensory alteration of the ocular surface-that is, higher levels of staining correlated with increased conjunctival chemical sensitivity. (ClinicalTrials.gov number, NCT00455455.).

Analysis of Cytokine Levels in Tears and Clinical Correlations After Intense Pulsed Light Treating Meibomian Gland Dysfunction.

PubMed

Liu, Ruixing; Rong, Bei; Tu, Ping; Tang, Yun; Song, Wenjing; Toyos, Rolando; Toyos, Melissa; Yan, Xiaoming

2017-11-01

To investigate the change from baseline of inflammatory markers in tears of dry eye disease (DED) subjects owing to meibomian gland dysfunction (MGD) after intense pulsed light (IPL) treatment and meibomian gland expression (MGE) compared to sham treatment, and the correlations with ocular surface parameters. Randomized, double-masked, controlled study. Those randomized into the active treatment arm received 3 consecutive treatments (14∼16 J/cm 2 ) approximately 4 weeks apart in the periocular region. Control eyes received 3 treatments in the same intervals of 0 J/cm 2 . Tear samples in all eyes were collected and analyzed at baseline, week 12, and/or week 4 for interleukin (IL)-17A, IL-6, and prostaglandin E2 (PGE2). The correlations between cytokines and ocular surface parameters were analyzed before and after IPL treatment. All of the inflammatory markers declined in value compared to baselines. IL-17A and IL-6 showed statistically significant decreases compared to sham treatment at each measured time point. PGE2 showed statistically significant decreases compared to sham at week 12. Results showed that the expressions of IL-17A and IL-6 correlated well with ocular surface parameters of the lower eyelid before IPL. The changed values of IL-6 and PGE2 in tears correlated with the changed values of partial ocular surface parameters after IPL treatment in study eyes, respectively. The study results suggest that IPL can significantly reduce inflammatory markers in tears of patients suffering with DED owing to MGD after IPL treatment. These findings indicate that IL-17A and IL-6 play roles in the pathogenesis of DED owing to MGD, and the reduction of the inflammatory factors is consistent with the improvement of partial clinical symptoms and signs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Microbial Contamination of Contact Lenses, Lens Care Solutions, and Their Accessories: A Literature Review

PubMed Central

Szczotka-Flynn, Loretta B.; Pearlman, Eric; Ghannoum, Mahmoud

2012-01-01

Purpose A contact lens (CL) can act as a vector for microorganisms to adhere to and transfer to the ocular surface. Commensal microorganisms that uneventfully cohabitate on lid margins and conjunctivae and potential pathogens that are found transiently on the ocular surface can inoculate CLs in vivo. In the presence of reduced tissue resistance, these resident microorganisms or transient pathogens can invade and colonize the cornea or conjunctiva to produce inflammation or infection. Methods The literature was reviewed and used to summarize the findings over the last 30 years on the identification, enumeration, and classification of microorganisms adherent to CLs and their accessories during the course of normal wear and to hypothesize the role that these microorganisms play in CL infection and inflammation. Results Lens handling greatly increases the incidence of lens contamination, and the ocular surface has a tremendous ability to destroy organisms. However, even when removed aseptically from the eye, more than half of lenses are found to harbor microorganisms, almost exclusively bacteria. Coagulase-negative Staphylococci are most commonly cultured from worn lenses; however, approximately 10% of lenses harbor Gram-negative and highly pathogenic species, even in asymptomatic subjects. In storage cases, the incidence of positive microbial bioburden is also typically greater than 50%. All types of care solutions can become contaminated, including up to 30% of preserved products. Conclusions The process of CL-related microbial keratitis and inflammation is thought to be preceded by the presence or transfer or both of microorganisms from the lens to the ocular surface. Thus, this detailed understanding of lens-related bioburden is important in the understanding of factors associated with infectious and inflammatory complications. Promising mechanisms to prevent bacterial colonization on lenses and lens cases are forthcoming, which may decrease the incidence of microbially driven CL complications. PMID:20168237

Release of complement regulatory proteins from ocular surface cells in infections.

PubMed

Cocuzzi, E; Guidubaldi, J; Bardenstein, D S; Chen, R; Jacobs, M R; Medof, E M

2000-11-01

The decay accelerating factor (DAF or CD55) and the membrane inhibitor of reactive lysis (MIRL or CD59), two complement regulatory proteins that protect self cells from autologous complement-mediated injury, are attached to corneal and cqonjunctival epithelial cells by glycosylphos-phatidylinositol (GPI) anchors. We sought to 1) determine the frequency with which bacteria recovered from patients with infections of the eye elaborate factors that can remove these surface proteins from ocular cells, 2) determine the spectrum of bacteria from other sites that have similar effects, and 3) establish the time interval required for reconstitution of the two regulators. Culture supernatants of 18 ocular isolates [P. aeruginosa (n = 3), S. marcescens (n = 1), S. epidermidis (n = 9), and S. aureus (n = 5)], and > 100 other clinical specimens isolated in the hospital's microbiology laboratory [P. mirabilis (n = 1), S. aureus (n = 65), S. epidermidis (n = 24), B. cereus (n = 12), H. influenzae (n = 15), and Enterobacter sp. (n = 21)] were incubated at 37 degrees C for various times with conjunctival epithelial cells, conjunctival fibroblasts or HeLa cells and the release of DAF and CD59 proteins from the surfaces of the cells analyzed by 2-site immunoradiometric assays and by Western blotting. The kinetics of recovery of DAF and CD59 expression on the cells was measured by flow cytometry. DAF and/or CD59 release from the cell monolayers varied from < 5% to > 99% at as much as a 1:81 dilution of the supernatant from some bacteria. On conjunctival epithelial cells, more than 8 hr was required for 44% recovery of DAF expression and for 50% recovery of CD59 expression. Bacteria produce phospholipases and/or other enzymes which can efficiently remove DAF and CD59 from ocular cell surfaces. This phenomenon may correlate with their in vivo pathogenicity.

Neurturin-deficient mice develop dry eye and keratoconjunctivitis sicca.

PubMed

Song, Xiu Jun; Li, De-Quan; Farley, William; Luo, Li Hui; Heuckeroth, Robert O; Milbrandt, Jeffrey; Pflugfelder, Stephen C

2003-10-01

Neurturin has been identified as a neurotrophic factor for parasympathetic neurons. Neurturin-deficient (NRTN(-/-)) mice have defective parasympathetic innervation of their lacrimal glands. This study was conducted to evaluate tear function and ocular surface phenotype in NRTN(-/-) mice. Determined by tail genomic DNA PCR, 25 NRTN(-/-) mice and 17 neurturin-normal (NRTN(+/+)) mice aged 6 weeks to 4 months were evaluated. Aqueous tear production, tear fluorescein clearance and corneal sensation were serially measured. Corneal permeability to AlexaFluor dextran (AFD; Molecular Probes, Eugene, OR) was measured by a fluorometric assay at 485 nm excitation and 530 nm emission. Histology was evaluated in PAS-stained sections. Mucin and HLA class II (IA) antigen were assessed by immunofluorescent staining. Tear IL-1beta was measured by ELISA, and tear matrix metalloproteinase (MMP)-9 by zymography. Gene expression in the corneal epithelia was analyzed by semiquantitative RT-PCR. In comparison to that in age-matched NRTN(+/+) mice, aqueous tear production, tear fluorescein clearance, and corneal sensation were significantly reduced in NRTN(-/-) mice, whereas corneal permeability to AFD was significantly increased. Immunoreactive MUC-4 and -5AC mucin and goblet cell density (P < 0.001) in the conjunctiva of NRTN(-/-) mice were lower than in NRTN(+/+) mice. The expression of MUC-1 and -4 mRNA by the corneal epithelium was reduced in NRTN(-/-) mice. There were a significantly greater number of IA antigen-positive conjunctival epithelial cells in NRTN(-/-) mice than NRTN(+/+) mice. Tear fluid IL-1beta and MMP-9 concentrations and the expression of IL-1beta, TNF-alpha, macrophage inflammatory protein (MIP)-2, cytokine-induced neutrophil chemoattractant (KC), and MMP-9 mRNA by the corneal epithelia were significantly increased in NRTN(-/-) mice, compared with NRTN(+/+) mice. Neurturin-deficient mice show phenotypic changes and ocular surface inflammation that mimic human keratoconjunctivitis sicca. This model supports the importance of a functional ocular surface-central nervous system-lacrimal gland sensory-autonomic neural network in maintaining ocular surface health and homeostasis.

Effects of Prolonged Reading on Dry Eye.

PubMed

Karakus, Sezen; Agrawal, Devika; Hindman, Holly B; Henrich, Claudia; Ramulu, Pradeep Y; Akpek, Esen K

2018-04-25

To demonstrate the effects of prolonged silent reading on tear film and ocular surface parameters. Prospective, observational clinical study. A total of 177 patients with dry eye and 34 normal controls aged 50 years and older. After evaluating symptoms using the Ocular Surface Disease Index (OSDI) questionnaire, the following tests were performed in consecutive order: automated noninvasive tear break-up time (TBUT), surface asymmetry and regularity indices, Schirmer's testing without anesthesia, corneal staining using fluorescein, and conjunctival staining using lissamine green. The participants were then asked to read a 30-minute validated passage silently. The tests were repeated after the reading task. Changes in tear film and ocular surface parameters after reading. All parameters, with the exception of surface asymmetry index, worsened after the reading task in patients with dry eye and in controls. The worsening reached a statistical significance for corneal and conjunctival staining in the dry eye group (P < 0.001) and for corneal staining in the control group (P < 0.01). At baseline, OSDI scores correlated only with corneal and conjunctival staining scores (r = 0.19, P = 0.006 and r = 0.27, P < 0.001). Among postreading measurements, baseline OSDI scores correlated with TBUT (r = -0.15, P = 0.03) in addition to corneal and conjunctival staining (r = 0.25, P < 0.001 and r = 0.22, P = 0.001). Changes in TBUT and Schirmer's test correlated significantly with their respective baseline values (r = -0.61, P < 0.001 and r = -0.44, P < 0.001), indicating that the more unstable the tear film and the lower the aqueous tear secretion, the worse they became after the prolonged reading task. Worsening in corneal staining directly correlated with the baseline conjunctival staining (r = 0.17, P = 0.02) and surface regularity index (r = 0.21, P = 0.01). Evaluating tear film and ocular surface parameters at rest may miss clinical findings brought about by common everyday tasks such as reading, leading to discordance between patient-reported symptoms and clinician-observed signs. Quantifying dry eye after visually straining activities such as prolonged silent reading may help better understand patient symptomatology. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Mucin characteristics of human corneal-limbal epithelial cells that exclude the rose bengal anionic dye.

PubMed

Argüeso, Pablo; Tisdale, Ann; Spurr-Michaud, Sandra; Sumiyoshi, Mika; Gipson, Ilene K

2006-01-01

Rose bengal is an organic anionic dye used to assess damage of the ocular surface epithelium in ocular surface disease. It has been proposed that mucins have a protective role, preventing rose bengal staining of normal ocular surface epithelial cells. The current study was undertaken to evaluate rose bengal staining in a human corneal-limbal epithelial (HCLE) cell line known to produce and glycosylate membrane-associated mucins. HCLE cells were grown to confluence in serum-free medium and switched to DMEM/F12 with 10% serum to promote differentiation. Immunolocalization of the membrane-associated mucins MUC1 and MUC16 and the T-antigen carbohydrate epitope was performed with the monoclonal antibodies HMFG-2 and OC125 and jacalin lectin, respectively. To assess dye uptake, cultures were incubated for 5 minutes with 0.1% rose bengal and photographed. To determine whether exclusion of negatively charged rose bengal requires a negative charge at the cell surface, cells were incubated with fluoresceinated cationized ferritin. The effect of hyperosmotic stress on rose bengal staining in vitro was evaluated by increasing the ion concentration (Ca+2 and Mg+2) in the rose bengal uptake assay. The cytoplasm and nucleus of confluent HCLE cells cultured in media without serum, lacking the expression of MUC16 but not MUC1, as well as human corneal fibroblasts, which do not express mucins, stained with rose bengal. Culture of HCLE cells in medium containing serum resulted in the formation of islands of stratified cells that excluded rose bengal. Apical cells of the stratified islands produced MUC16 and the T-antigen carbohydrate epitope on their apical surfaces. Colocalization experiments demonstrated that fluoresceinated cationized ferritin did not bind to these stratified cells, indicating that rose bengal is excluded from cells that lack negative charges. Increasing the amounts of divalent cations in the media reduced the cellular area protected against rose bengal uptake. These results indicate that stratification and differentiation of corneal epithelial cells, as measured by the capacity to produce the membrane-associated mucin MUC16 and the mucin-associated T-antigen carbohydrate on their apical surfaces provide protection against rose bengal penetrance in vitro and suggest a role for membrane-associated mucins and their oligosaccharides in the protection of ocular surface epithelia.

Mucin Characteristics of Human Corneal-Limbal Epithelial Cells that Exclude the Rose Bengal Anionic Dye

PubMed Central

Argüeso, Pablo; Tisdale, Ann; Spurr-Michaud, Sandra; Sumiyoshi, Mika; Gipson, Ilene K.

2005-01-01

Purpose Rose bengal is an organic anionic dye used to assess damage of the ocular surface epithelium in ocular surface disease. It has been proposed that mucins have a protective role, preventing rose bengal staining of normal ocular surface epithelial cells. The current study was undertaken to evaluate rose bengal staining in a human corneal-limbal epithelial (HCLE) cell line known to produce and glycosylate membrane-associated mucins. Methods HCLE cells were grown to confluence in serum-free medium and switched to DMEM/F12 with 10% serum to promote differentiation. Immunolocalization of the membrane-associated mucins MUC1 and MUC16 and the T-antigen carbohydrate epitope was performed with the monoclonal antibodies HMFG-2 and OC125 and jacalin lectin, respectively. To assess dye uptake, cultures were incubated for 5 minutes with 0.1% rose bengal and photographed. To determine whether exclusion of negatively charged rose bengal requires a negative charge at the cell surface, cells were incubated with fluoresceinated cationized ferritin. The effect of hyperosmotic stress on rose bengal staining in vitro was evaluated by increasing the ion concentration (Ca+2 and Mg+2) in the rose bengal uptake assay. Results The cytoplasm and nucleus of confluent HCLE cells cultured in media without serum, lacking the expression of MUC16 but not MUC1, as well as human corneal fibroblasts, which do not express mucins, stained with rose bengal. Culture of HCLE cells in medium containing serum resulted in the formation of islands of stratified cells that excluded rose bengal. Apical cells of the stratified islands produced MUC16 and the T-antigen carbohydrate epitope on their apical surfaces. Colocalization experiments demonstrated that fluoresceinated cationized ferritin did not bind to these stratified cells, indicating that rose bengal is excluded from cells that lack negative charges. Increasing the amounts of divalent cations in the media reduced the cellular area protected against rose bengal uptake. Conclusions These results indicate that stratification and differentiation of corneal epithelial cells, as measured by the capacity to produce the membrane-associated mucin MUC16 and the mucin-associated T-antigen carbohydrate on their apical surfaces provide protection against rose bengal penetrance in vitro and suggest a role for membrane-associated mucins and their oligosaccharides in the protection of ocular surface epithelia. PMID:16384952

The effects of 2 week senofilcon-A silicone hydrogel contact lens daily wear on tear functions and ocular surface health status.

PubMed

Dogru, Murat; Ward, Samantha K; Wakamatsu, Tais; Ibrahim, Osama; Schnider, Cristina; Kojima, Takashi; Matsumoto, Yukihiro; Ogawa, Junko; Shimazaki, Jun; Tsubota, Kazuo

2011-04-01

To prospectively investigate the effects of 2 week senofilcon A contact lens (CL) daily wear on the functional visual acuity (VA), ocular surface and tear film. Seventeen right eyes of 17 senofilcon A CL wearers without any ocular or systemic diseases were examined before and 2 weeks after lens wear. Visual acuity measurements, tear evaporation rate, ELISA for tear cytokines, strip meniscometry, tear lipid layer interferometry, tear film break-up time (BUT), in vivo confocal microscopy, corneal sensitivity, ocular surface vital staining, Schirmer I test and brush cytology for MUC5AC mRNA expression were performed before and after CL wear. The best corrected Landolt VA, functional VA parameters, the mean lipid layer interferometry grades, tear evaporation rates, Schirmer test values, vital staining scores and in vivo confocal microscopy parameters did not show any significant differences after 2 weeks of CL wear. The tear film BUT showed a significant decrease together with a significant down regulation of MUC5 AC mRNA expression after CL wear. A statistically significant elevation in the mean tear interleukin (IL)-6 concentration was also observed after 2 weeks of CL wear. Two week senofilcon A daily CL wear seems to be associated with tear instability, a decrease in MUC5AC expression, and elevation of IL-6 in tears without significant alterations in epithelial damage scores or in the morphology or density of in vivo keratoconjunctival cells and nerves. Alterations associated with long term wear and patients with dry eye disease need to be studied in future trials. Copyright © 2010 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Frequency and risk factors associated with dry eye in patients attending a tertiary care ophthalmology center in Mexico City

PubMed Central

Martinez, Jaime D; Galor, Anat; Ramos-Betancourt, Nallely; Lisker-Cervantes, Andrés; Beltrán, Francisco; Ozorno-Zárate, Jorge; Sánchez-Huerta, Valeria; Torres-Vera, Marco-Antonio; Hernández-Quintela, Everardo

2016-01-01

Purpose The purpose of this study was to ascertain the frequency and risk factors of dry eye (DE) among patients attending a tertiary care ophthalmology center in Mexico. Methods Approximately 338 consecutive new patients attending a tertiary care ophthalmology center in Mexico City underwent an ocular surface examination, which included tear film break-up time, fluorescein corneal staining, Schirmer’s test, and evaluation of meibum quality. Symptoms of DE were evaluated by the Ocular Surface Disease Index and Dry Eye Questionnaire-5. Information on demographics, exposures, past medical and ocular history, and medications was also collected. Results The frequency of severe DE symptoms was found to be 43% based on the Ocular Surface Disease Index and 30% based on Dry Eye Questionnaire-5. Risk factors significantly associated with increased DE symptoms included dry mouth and gastrointestinal ulcer medications. With regard to signs, aqueous tear deficiency was a less-frequent finding (22%) in our population than evaporative deficiency (94%). Risk factors associated with aqueous tear deficiency were dry mouth and diuretic use. No risk factors were associated with evaporative deficiency. Risk factors associated with meibomian gland dysfunction included old age, male sex, arthritis, and use of an antihypertensive. The only risk factor associated with corneal staining was dry mouth. Conclusion This is the first study to demonstrate the frequency of symptomatic and clinical DE in a tertiary care ophthalmology center in Mexico. The frequency of DE ranged from 30% using a symptomatic definition to 94% using objective measures. Different risk factors were found for different aspects of DE, suggesting differing underlying pathophysiologies behind different DE subtypes. PMID:27499613

Can We Improve the Tolerance of an Ocular Prosthesis by Enhancing Its Surface Finish?

PubMed

Litwin, Andre S; Worrell, Emma; Roos, Jonathan C P; Edwards, Barry; Malhotra, Raman

Patients who wear an ocular prosthesis frequently suffer with dry eye symptoms and socket discharge, often on a daily basis. The aim of the study was to determine whether a smoother, optical quality polish of the prosthesis' surface could improve symptoms and wear tolerance. The study was designed as single-center, single-masked, prospective randomized controlled trial. Eighty-eight consecutive patients undergoing annual ocular prosthesis maintenance review were approached from the prosthesis clinic. Forty-one out of 49 eligible patients were recruited. Participants were randomized to either a standard or a higher "optical quality" polish of their prosthesis. At entry to the trial, at 1 month, and 12 months they completed a questionnaire covering cleaning, lubricant use, inflammation, discomfort, and discharge. Lower scores indicated better tolerance of the prosthesis. At each visit, the prosthesis was stained and photographed against a standard background to assess deposit build up. Primary outcome measures were 1) a subjective questionnaire score and 2) an objective assessment of surface deposit build-up on prosthetic eyes by standardized photographic grading. Forty-one patients participated in the study. The median age of their prosthesis was 36 months (range 9 months-40 years). There was no statistically significant difference in questionnaire scores or deposit build up between the 2 groups at baseline. By 12-months, the higher optical quality polish showed a statistically significant reduction in symptoms and frequency of discharge (2.19 vs. 3.85; p = 0.05-lower scores better). Scoring of the prosthesis' deposit build-up showed a significant difference at 1 month, but this was not sustained at 12 months. Creating an optical quality finish to an ocular prosthesis reduces deposit build up on artificial eyes. The authors found this modification improved patient tolerance at 12 months.

Therapeutic potential of trichostatin A to control inflammatory and fibrogenic disorders of the ocular surface.

PubMed

Kitano, Ai; Okada, Yuka; Yamanka, Osamu; Shirai, Kumi; Mohan, Rajiv R; Saika, Shizuya

2010-12-31

To examine the effects of a histone deacetylase inhibitor, Trichostatin A (TSA), on the behavior of macrophages and subconjunctival fibroblasts in vitro and on ocular surface inflammation and scarring in vivo using an alkali burn wound healing model. Effects of TSA on expression of inflammation-related growth factors or collagen I were examined by real-time RT-PCR or immunoassay in mouse macrophages or human subconjunctival fibroblasts. Effects of TSA on trans forming growth factor β (TGFβ)/Smad signaling were evaluated with western blotting and/or immunocytochemistry. Alkali-burn injuries on the eyes of mice were performed with three µl of 0.5 N NaOH under general and topical anesthesia. TSA (600 µg/Kg daily) or vehicle was administered to animals via intraperitoneal (i.p.) injection. Histology and real-time RT-PCR investigations evaluated the effects of TSA on the healing process of the cornea. TSA inhibited TGFβ 1 and vascular endothelial growth factor (VEGF) expression in macrophages, and TGFβ1 and collagen I in ocular fibroblasts. It elevated the expression of 5'-TG-3'-interacting factor (TGIF) and Smad7 in fibroblasts and blocked nuclear translocation of phospho-Smad2. Real-time PCR and immunocytochemistry studies showed that systemic administration of TSA suppressed the inflammation and fibrotic response in the stroma and accelerated epithelial healing in the alkali-burned mouse cornea. Systemic administration of TSA reduces inflammatory and fibrotic responses in the alkali-burned mouse ocular surface in vivo. The mechanisms of action involve attenuation of Smad signal in mesenchymal cells and reduction in the activation and recruitment of macrophages. TSA has the potential to treat corneal scarring in vivo.

Chemokine receptors CCR6 and CXCR3 are necessary for CD4(+) T cell mediated ocular surface disease in experimental dry eye disease.

PubMed

Coursey, Terry G; Gandhi, Niral B; Volpe, Eugene A; Pflugfelder, Stephen C; de Paiva, Cintia S

2013-01-01

CD4(+) T cells are essential to pathogenesis of ocular surface disease in dry eye. Two subtypes of CD4(+) T cells, Th1 and Th17 cells, function concurrently in dry eye to mediate disease. This occurs in spite of the cross-regulation of IFN-γ and IL-17A, the prototypical cytokines Th1 and Th17 cells, respectively. Essential to an effective immune response are chemokines that direct and summon lymphocytes to specific tissues. T cell trafficking has been extensively studied in other models, but this is the first study to examine the role of chemokine receptors in ocular immune responses. Here, we demonstrate that the chemokine receptors, CCR6 and CXCR3, which are expressed on Th17 and Th1 cells, respectively, are required for the pathogenesis of dry eye disease, as CCR6KO and CXCR3KO mice do not develop disease under desiccating stress. CD4(+) T cells from CCR6KO and CXCR3KO mice exposed to desiccating stress (DS) do not migrate to the ocular surface, but remain in the superficial cervical lymph nodes. In agreement with this, CD4(+) T cells from CCR6 and CXCR3 deficient donors exposed to DS, when adoptively transferred to T cell deficient recipients manifest minimal signs of dry eye disease, including significantly less T cell infiltration, goblet cell loss, and expression of inflammatory cytokine and matrix metalloproteinase expression compared to wild-type donors. These findings highlight the important interaction of chemokine receptors on T cells and chemokine ligand expression on epithelial cells of the cornea and conjunctiva in dry eye pathogenesis and reveal potential new therapeutic targets for dry eye disease.

Chemokine Receptors CCR6 and CXCR3 Are Necessary for CD4+ T Cell Mediated Ocular Surface Disease in Experimental Dry Eye Disease

PubMed Central

Coursey, Terry G.; Gandhi, Niral B.; Volpe, Eugene A.; Pflugfelder, Stephen C.; de Paiva, Cintia S.

2013-01-01

CD4+ T cells are essential to pathogenesis of ocular surface disease in dry eye. Two subtypes of CD4+ T cells, Th1 and Th17 cells, function concurrently in dry eye to mediate disease. This occurs in spite of the cross-regulation of IFN-γ and IL-17A, the prototypical cytokines Th1 and Th17 cells, respectively. Essential to an effective immune response are chemokines that direct and summon lymphocytes to specific tissues. T cell trafficking has been extensively studied in other models, but this is the first study to examine the role of chemokine receptors in ocular immune responses. Here, we demonstrate that the chemokine receptors, CCR6 and CXCR3, which are expressed on Th17 and Th1 cells, respectively, are required for the pathogenesis of dry eye disease, as CCR6KO and CXCR3KO mice do not develop disease under desiccating stress. CD4+ T cells from CCR6KO and CXCR3KO mice exposed to desiccating stress (DS) do not migrate to the ocular surface, but remain in the superficial cervical lymph nodes. In agreement with this, CD4+ T cells from CCR6 and CXCR3 deficient donors exposed to DS, when adoptively transferred to T cell deficient recipients manifest minimal signs of dry eye disease, including significantly less T cell infiltration, goblet cell loss, and expression of inflammatory cytokine and matrix metalloproteinase expression compared to wild-type donors. These findings highlight the important interaction of chemokine receptors on T cells and chemokine ligand expression on epithelial cells of the cornea and conjunctiva in dry eye pathogenesis and reveal potential new therapeutic targets for dry eye disease. PMID:24223818

Long-term effect of BAK-free travoprost on ocular surface and intraocular pressure in glaucoma patients after transition from latanoprost.

PubMed

Aihara, Makoto; Otani, Shin-ichiro; Kozaki, Jun; Unoki, Kazuhiko; Takeuchi, Masamitsu; Minami, Keiichiro; Miyata, Kazunori

2012-01-01

To assess the efficacy and tolerability of benzalkonium chloride (BAK)-free travoprost after transition from BAK-preserved latanoprost. This was a prospective, open-label, multicenter study in patients with open-angle glaucoma or ocular hypertension who had been treated with latanoprost monotherapy for at least 3 months. The main outcome measures were superficial punctate keratopathy (SPK), hyperemia, and intraocular pressure (IOP). At baseline, 1, 3, and 12 months, hyperemia, SPK, and IOP were consecutively assessed. Hyperemia was assessed using a 4-grade scale. SPK was assessed by fluorescence staining observed by Area-Density classification. The IOP was measured by Goldmann applanation tonometry. One hundred and fourteen patients participated in this study. Twenty-eight patients discontinued medications by 1 month. Sixty-seven patients completed the study. Transition from latanoprost to BAK-free travoprost showed no significant effect on hyperemia at 1 month, but showed significant decreases at 3 and 12 months compared with baseline (P<0.05). The prevalence of SPK, especially its severity score, at all points were significantly reduced compared with baseline (P<0.05). The IOP at baseline and at 12 months after transition was 14.9±3.4 and 14.3±3.3 mm Hg, indicating a significant reduction after the change in regimen compared with baseline (P<0.05). Treatment for 12 months with BAK-free travoprost after BAK-preserved latanoprost resulted in fewer ocular surface complications, as indicated by the reduced prevalence of SPK and decreased hyperemia, and no clinically relevant changes in IOP. BAK-free travoprost may have beneficial effects on the ocular surface while showing IOP-lowering efficacy comparable with BAK-preserved eye drops.

Evaluation of lipid oxidative stress status and inflammation in atopic ocular surface disease

PubMed Central

Wakamatsu, Tais H.; Ayako, Igarashi; Takano, Yoji; Matsumoto, Yukihiro; Ibrahim, Osama M.A.; Okada, Naoko; Satake, Yoshiyuki; Fukagawa, Kazumi; Shimazaki, Jun; Tsubota, Kazuo; Fujishima, Hiroshi

2010-01-01

Background Although the oxidative stress status in atopic skin disease has been reported to be elevated, there are still no studies related to the status of oxidative stress in atopic ocular surface disease. The purpose of this study was to evaluate the ocular surface lipid oxidative stress status and inflammation in atopic keratoconjunctivitis (AKC) patients and normal subjects. Methods Twenty eight eyes of 14 patients (9 males, 5 females) with AKC and 18 eyes of 9 age and sex matched (4 males and 5 females) normal healthy controls were examined in this prospective study. The severity of atopic dermatitis (AD) was scored by the SCORing Atopic Dermatitis (SCORAD) index. All subjects underwent Schirmer test, tear film break up time (BUT), fluorescein/Rose Bengal stainings, tear collection, and brush cytology from the upper palpebral conjunctiva. The brush cytology samples were stained with Diff-Quik for differentiation of inflammatory cells and immunohistochemistry (IHC) staining with HEL (hexanoyl-lysine) and 4-HNE (4-hydroxy-2-nonenal) to study lipid oxidation. HEL and cytokine (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ)) levels were measured by enzyme-linked immunosorbent assay (ELISA) from tear samples of AKC patients and control subjects. Toluidine Blue and IHC staining with HEL, 4-HNE and cluster of differentiation 45 (CD45) were performed on papillary samples of AKC patients. This study was conducted in compliance with the “Declaration of Helsinki.” Results The tear stability and vital staining scores were significantly worse in eyes of AKC patients (p<0.05) compared to the controls. Inflammatory cells and positively stained conjunctival epithelial cells for HEL and 4-HNE showed a significant elevation in brush cytology samples of AKC patients. Significantly higher levels of HEL and cytokines were detected in tears of AKC patients compared to controls. Papillary specimens also revealed many CD45 inflammatory cells as well as many cells positively stained with HEL and 4-HNE in IHC. A strong significant linear positive correlation between conjunctival inflammation and epithelial lipid oxidative stress status was observed. Conjunctival lipid oxidative stress also correlated strongly with tear HEL levels and epithelial damage scores. Conclusions The ocular surface disease in AKC was characterized by marked tear instability, ocular surface epithelial damage, increase in inflammatory infiltrates and presence of increased lipid oxidation. PMID:21139696

Optimised laser microdissection of the human ocular surface epithelial regions for microarray studies

PubMed Central

2013-01-01

Background The most important challenge of performing insitu transcriptional profiling of the human ocular surface epithelial regions is obtaining samples in sufficient amounts, without contamination from adjacent tissue, as the region of interest is microscopic and closely apposed to other tissues regions. We have effectively collected ocular surface (OS) epithelial tissue samples from the Limbal Epithelial Crypt (LEC), limbus, cornea and conjunctiva of post-mortem cadaver eyes with laser microdissection (LMD) technique for gene expression studies with spotted oligonucleotide microarrays and Gene 1.0 ST arrays. Methods Human donor eyes (4 pairs for spotted oligonucleotide microarrays, 3 pairs for Gene 1.0 ST arrays) consented for research were included in this study with due ethical approval of the Nottingham Research Ethics Committee. Eye retrieval was performed within 36 hours of post-mortem period. The dissected corneoscleral buttons were immersed in OCT media and frozen in liquid nitrogen and stored at −80°C till further use. Microscopic tissue sections of interest were taken on PALM slides and stained with Toluidine Blue for laser microdissection with PALM microbeam systems. Optimisation of the laser microdissection technique was crucial for efficient and cost effective sample collection. Results The starting concentration of RNA as stipulated by the protocol of microarray platforms was taken as the cut-off concentration of RNA samples in our studies. The area of LMD tissue processed for spotted oligonucleotide microarray study ranged from 86,253 μm2 in LEC to 392,887 μm2 in LEC stroma. The RNA concentration of the LMD samples ranged from 22 to 92 pg/μl. The recommended starting concentration of the RNA samples used for Gene 1.0 ST arrays was 6 ng/5 μl. To achieve the desired RNA concentration the area of ocular surface epithelial tissue sample processed for the Gene 1.0 ST array experiments was approximately 100,0000 μm2 to 130,0000 μm2. RNA concentration of these samples ranged from 10.88 ng/12 μl to 25.8 ng/12 μl, with the RNA integrity numbers (RIN) for these samples from 3.3 to 7.9. RNA samples with RIN values below 2, that had failed to amplify satisfactorily were discarded. Conclusions The optimised protocol for sample collection and laser microdissection improved the RNA yield of the insitu ocular surface epithelial regions for effective microarray studies on spotted oligonucleotide and affymetrix platforms. PMID:24160452

Nanoparticles in the ocular drug delivery

PubMed Central

Zhou, Hong-Yan; Hao, Ji-Long; Wang, Shuang; Zheng, Yu; Zhang, Wen-Song

2013-01-01

Ocular drug transport barriers pose a challenge for drug delivery comprising the ocular surface epithelium, the tear film and internal barriers of the blood-aqueous and blood-retina barriers. Ocular drug delivery efficiency depends on the barriers and the clearance from the choroidal, conjunctival vessels and lymphatic. Traditional drug administration reduces the clinical efficacy especially for poor water soluble molecules and for the posterior segment of the eye. Nanoparticles (NPs) have been designed to overcome the barriers, increase the drug penetration at the target site and prolong the drug levels by few internals of drug administrations in lower doses without any toxicity compared to the conventional eye drops. With the aid of high specificity and multifunctionality, DNA NPs can be resulted in higher transfection efficiency for gene therapy. NPs could target at cornea, retina and choroid by surficial applications and intravitreal injection. This review is concerned with recent findings and applications of NPs drug delivery systems for the treatment of different eye diseases. PMID:23826539

Vestibular evoked myogenic potentials (VEMPs) in central neurological disorders.

PubMed

Venhovens, J; Meulstee, J; Verhagen, W I M

2016-01-01

Several types of acoustic stimulation (i.e. tone bursts or clicks), bone-conducted vibration, forehead taps, and galvanic stimulation elicit myogenic potentials. These can be recorded in cervical and ocular muscles, the so called vestibular evoked myogenic potentials (VEMPs). The cervical VEMP (cVEMP) resembles the vestibulo-collic reflex and the responses can be recorded from the ipsilateral sternocleidomastoid muscle. The ocular VEMP resembles the vestibulo-ocular reflex and can be recorded from extra-ocular muscles by a surface electrode beneath the contralateral infraorbital margin. Initially, the literature concerning VEMPs was limited to peripheral vestibular disorders, however, the field of VEMP testing is rapidly expanding, with an increasing focus on central neurological disorders. The current literature concerning VEMP abnormalities in central neurological disorders is critically reviewed, especially regarding the methodological aspects in relation to quality as well as the clinical interpretation of the VEMP results. Suggestions for further research are proposed as well as some clinically useful indications. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

The improvement of dry eye after cataract surgery by intraoperative using ophthalmic viscosurgical devices on the surface of cornea

PubMed Central

He, Yuan; Li, Jia; Zhu, Jingfen; Jie, Ying; Wang, Ningli; Wang, Jun

2017-01-01

Abstract Backgroud: This study aimed to investigate the protective effect of intraoperative used hydroxypropyl methylcellulose (HPMC 2%) on the ocular surface after cataract surgery. Methods: A total of 149 eyes (149 patients) diagnosed with age-related cataract, age 69.19 ± 9.74 years, were enrolled in this prospective, parallel-design, continuous, randomised controlled study. Patients were randomly assigned to receive HPMC 2% (study group) or balanced salt solution (control group) during the surgery to moisturize the cornea surface. The Ocular Surface Disease Index, Schirmer test without topical anesthetics, tear break-up time, and corneal fluorescein staining were assessed preoperatively, 1 day, 1 week, and 1 month after the surgery, respectively. Results: The Schirmer test value of male patients in the study group at 1 week postoperation was higher than that of male patients in the control group (P = .019). For patients diagnosed with dry eye before the surgery, Schirmer test value in the male patients in the study group at 1 month after surgery was higher than that in the male patients in the control group (P = .037). Furthermore, for the cluster of preoperative dry eye patients whose surgical time was longer than median, corneal fluorescein staining of the patients in the study group was superior to that of the patients in the control group (P = .032). Conclusion: Intraoperative use of HPMC 2% on the cornea surface could improve clinical outcomes of tear film and ocular surface health to some degree, especially in the patients diagnosed with dry eye before the surgery, male patients, and patients whose surgical time was relatively longer. PMID:29390284

Correlation of corneal thickness, endothelial cell density and anterior chamber depth with ocular surface temperature in normal subjects.

PubMed

Pattmöller, Johanna; Wang, Jiong; Zemova, Elena; Seitz, Berthold; Eppig, Timo; Langenbucher, Achim; Szentmáry, Nóra

2015-09-01

To analyze corneal surface temperature profile in a young and healthy study population and to determine the impact of corneal thickness (CT), anterior chamber depth (ACD), and endothelial cell density (ECD) on surface temperature. In this prospective, single-center study 61 healthy right eyes of 61 subjects without tear film pathologies (mean age 24.9 ± 6.7 years) were recruited. Ocular surface temperature (OST) was measured with the Ocular Surface Thermographer TG-1000. From Pentacam HR CT and ACD, and from specular microscopy ECD and central corneal thickness (CCT) were acquired. From the raw measurement data (OST, CT and ACD) we extracted a) local OST the corneal center and 3mm away from the center at the 3, 6, and 9 o'clock positions, and b) Zernike parameters Z1, Z2 and Z3 to evaluate the general temperature profile within a 6mm circular area around the center. Overall, there was no correlation between OST and CT, ACD or ECD. Local OST did not correlate with CT at any measurement position. On average local OST was highest at measurement positions where CT was lowest, but without reaching statistical significance. Baseline OST was highest at thin corneal regions and temperature decay over time was smallest in those regions. Z1, Z2 and Z3 correlated well with CT. In healthy subjects corneal thickness, endothelial cell density and anterior chamber depth have no effect on corneal surface temperature. The general temperature profile seems to be influenced by the corneal thickness profile effecting a higher temperature and lower decay at thinner corneal regions. Copyright © 2014. Published by Elsevier GmbH.

Ganetespib Window of Opportunity Study in Head and Neck Cancers

ClinicalTrials.gov

2016-07-22

Stage I Hypopharyngeal Squamous Cell Carcinoma; Stage I Laryngeal Squamous Cell Carcinoma; Stage I Oral Cavity Squamous Cell Carcinoma; Stage I Oropharyngeal Squamous Cell Carcinoma; Stage II Hypopharyngeal Squamous Cell Carcinoma; Stage II Laryngeal Squamous Cell Carcinoma; Stage II Oral Cavity Squamous Cell Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma

The relationship between demodex and ocular discomfort.

PubMed

Lee, Seok Hyun; Chun, Yeoun Sook; Kim, Jae Hoon; Kim, Eung Suk; Kim, Jae Chan

2010-06-01

To determine the correlative relationship between the prevalence of Demodex in eyelashes and the severity of ocular discomfort, by investigating the demographic epidemiology associated with Demodex. One hundred seventy patients underwent epilation of four eyelashes of each eye, and the number of Demodex was counted. The patients answered questionnaires about ocular surface discomfort and underwent ophthalmic examinations, including slit lamp, tear film breakup time (BUT), Schirmer test, and microbial culturing. The correlative relationship between the number of Demodex and these variable data was analyzed. Demodex was found in 120 (70%) of the 170 tested patients. Of 1360 eyelashes, 740 (54%) had Demodex. There was no significant difference in the prevalence of Demodex between males and females (P = 0.35). The number of Demodex showed significant positive correlations with increased age, ocular discomfort, and 1/BUT (P < 0.001), but not with the Schirmer scores. The number of Demodex was significantly higher in patients with conjunctival papillary hypertrophy than in those without (P = 0.003). The presence or distribution of bacteria on eyelashes was similar between eyelids with and without Demodex. However, methicillin-resistant Staphylococcus aureus (MRSA) was detected more often on eyelids with Demodex, but this difference was not statistically significant. There is a strong correlation between the number of Demodex and the severity of ocular discomfort, suggesting that Demodex plays a pathogenic role in the ocular discomfort linked with aging.

Eye and orbit ultrasound

MedlinePlus

Echography - eye orbit; Ultrasound - eye orbit; Ocular ultrasonography; Orbital ultrasonography ... eye is numbed with medicine (anesthetic drops). The ultrasound wand (transducer) is placed against the front surface ...

Agrin and Perlecan Mediate Tumorigenic Processes in Oral Squamous Cell Carcinoma

PubMed Central

Kawahara, Rebeca; Granato, Daniela C.; Carnielli, Carolina M.; Cervigne, Nilva K.; Oliveria, Carine E.; Martinez, César A. R.; Yokoo, Sami; Fonseca, Felipe P.; Lopes, Marcio; Santos-Silva, Alan R.; Graner, Edgard; Coletta, Ricardo D.; Leme, Adriana Franco Paes

2014-01-01

Oral squamous cell carcinoma is the most common type of cancer in the oral cavity, representing more than 90% of all oral cancers. The characterization of altered molecules in oral cancer is essential to understand molecular mechanisms underlying tumor progression as well as to contribute to cancer biomarker and therapeutic target discovery. Proteoglycans are key molecular effectors of cell surface and pericellular microenvironments, performing multiple functions in cancer. Two of the major basement membrane proteoglycans, agrin and perlecan, were investigated in this study regarding their role in oral cancer. Using real time quantitative PCR (qRT-PCR), we showed that agrin and perlecan are highly expressed in oral squamous cell carcinoma. Interestingly, cell lines originated from distinct sites showed different expression of agrin and perlecan. Enzymatically targeting chondroitin sulfate modification by chondroitinase, oral squamous carcinoma cell line had a reduced ability to adhere to extracellular matrix proteins and increased sensibility to cisplatin. Additionally, knockdown of agrin and perlecan promoted a decrease on cell migration and adhesion, and on resistance of cells to cisplatin. Our study showed, for the first time, a negative regulation on oral cancer-associated events by either targeting chondroitin sulfate content or agrin and perlecan levels. PMID:25506919

Fundoscopy Exam

NASA Image and Video Library

2015-08-05

ISS044E033352 (08/05/2015) --- NASA astronaut Scott Kelly (left) assists Japan Aerospace Exploration Agency (JAXA) astronaut Kimiya Yui (right) with measurements for the ongoing Ocular Health study. Yui is seen operating a device called a Fundoscope which is used to take images of the retinal surface of an astronaut’s eye. Ocular Health is gathering data on crew visual health during and after long-duration space station missions to characterize how living in microgravity can affect the visual, vascular and central nervous systems.

Model-based conifer crown surface reconstruction from multi-ocular high-resolution aerial imagery

NASA Astrophysics Data System (ADS)

Sheng, Yongwei

2000-12-01

Tree crown parameters such as width, height, shape and crown closure are desirable in forestry and ecological studies, but they are time-consuming and labor intensive to measure in the field. The stereoscopic capability of high-resolution aerial imagery provides a way to crown surface reconstruction. Existing photogrammetric algorithms designed to map terrain surfaces, however, cannot adequately extract crown surfaces, especially for steep conifer crowns. Considering crown surface reconstruction in a broader context of tree characterization from aerial images, we develop a rigorous perspective tree image formation model to bridge image-based tree extraction and crown surface reconstruction, and an integrated model-based approach to conifer crown surface reconstruction. Based on the fact that most conifer crowns are in a solid geometric form, conifer crowns are modeled as a generalized hemi-ellipsoid. Both the automatic and semi-automatic approaches are investigated to optimal tree model development from multi-ocular images. The semi-automatic 3D tree interpreter developed in this thesis is able to efficiently extract reliable tree parameters and tree models in complicated tree stands. This thesis starts with a sophisticated stereo matching algorithm, and incorporates tree models to guide stereo matching. The following critical problems are addressed in the model-based surface reconstruction process: (1) the problem of surface model composition from tree models, (2) the occlusion problem in disparity prediction from tree models, (3) the problem of integrating the predicted disparities into image matching, (4) the tree model edge effect reduction on the disparity map, (5) the occlusion problem in orthophoto production, and (6) the foreshortening problem in image matching, which is very serious for conifer crown surfaces. Solutions to the above problems are necessary for successful crown surface reconstruction. The model-based approach was applied to recover the canopy surface of a dense redwood stand using tri-ocular high-resolution images scanned from 1:2,400 aerial photographs. The results demonstrate the approach's ability to reconstruct complicated stands. The model-based approach proposed in this thesis is potentially applicable to other surfaces recovering problems with a priori knowledge about objects.

Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery

PubMed Central

Vasconcelos, Aimee; Vega, Estefania; Pérez, Yolanda; Gómara, María J; García, María Luisa; Haro, Isabel

2015-01-01

In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)–polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen’s egg test–chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery. PMID:25670897

Coupling Osmolarity Dynamics within Human Tear Film on an Eye-Shaped Domain

NASA Astrophysics Data System (ADS)

Li, Longfei; Braun, R. J.; Driscoll, T. A.; Henshaw, W. D.; Banks, J. W.; King-Smith, P. E.

2013-11-01

The concentration of ions in the tear film (osmolarity) is a key variable in understanding dry eye symptoms and disease. We derived a mathematical model that couples osmolarity (treated as a single solute) and fluid dynamics within the tear film on a 2D eye-shaped domain. The model concerns the physical effects of evaporation, surface tension, viscosity, ocular surface wettability, osmolarity, osmosis and tear fluid supply and drainage. We solved the governing system of coupled nonlinear PDEs using the Overture computational framework developed at LLNL, together with a new hybrid time stepping scheme (using variable step BDF and RKC) that was added to the framework. Results of our numerical simulations show good agreement with existing 1D models (for both tear film and osmolarity dynamics) and provide new insight about the osmolarity distribution over the ocular surface during the interblink.

Intracellular trafficking of hyaluronic acid-chitosan oligomer-based nanoparticles in cultured human ocular surface cells.

PubMed

Contreras-Ruiz, Laura; de la Fuente, María; Párraga, Jenny E; López-García, Antonio; Fernández, Itziar; Seijo, Begoña; Sánchez, Alejandro; Calonge, Margarita; Diebold, Yolanda

2011-01-27

Nanoparticles are a promising alternative for ocular drug delivery, and our group has proposed that they are especially suited for ocular mucosal disorders. The goal of the present study was to determine which internalization pathway is used by cornea-derived and conjunctiva-derived cell lines to take up hyaluronic acid (HA)-chitosan oligomer (CSO)-based nanoparticles (HA-CSO NPs). We also determined if plasmids loaded onto the NPs reached the cell nucleus. HA-CSO NPs were made of fluoresceinamine labeled HA and CSO by ionotropic gelation and were conjugated with a model plasmid DNA for secreted alkaline phosphatase. Human epithelial cell lines derived from the conjunctiva and the cornea were exposed to HA-CSO NPs for 1 h and the uptake was investigated in living cells by fluorescence microscopy. The influence of temperature and metabolic inhibition, the effect of blocking hyaluronan receptors, and the inhibition of main endocytic pathways were studied by fluorometry. Additionally, the metabolic pathways implicated in the degradation of HA-CSO NPs were evaluated by lysosome identification. There was intracellular localization of plasmid-loaded HACSO NPs in both corneal and conjunctival cells. The intracellular presence of NPs diminished with time. HA-CSO NP uptake was significantly reduced by inhibition of active transport at 4 °C and by sodium azide. Uptake was also inhibited by blocking hyaluronan receptors with anti-CD44 Hermes-1 antibody, by excess HA, and by filipin, an inhibitor of caveolin-dependent endocytosis. HA-CSO NPs had no effect on cell viability. The transfection efficiency of the model plasmid was significantly higher in NP treated cells than in controls. HA-CSO NPs were internalized by two different ocular surface cell lines by an active transport mechanism. The uptake was mediated by hyaluronan receptors through a caveolin-dependent endocytic pathway, yielding remarkable transfection efficiency. Most of HA-CSO NPs were metabolized within 48 h. This uptake did not compromise cell viability. These findings further support the potential use of HA-CSO NPs to deliver genetic material to the ocular surface.

Effect of benzalkonium chloride-free latanoprost ophthalmic solution on ocular surface in patients with glaucoma.

PubMed

Walimbe, Tejaswini; Chelerkar, Vidya; Bhagat, Purvi; Joshi, Abhijeet; Raut, Atul

2016-01-01

Benzalkonium chloride (BAK), included as a preservative in many topical treatments for glaucoma, induces significant toxicity and alters tear breakup time (TBUT). BAK-containing latanoprost, an ester prodrug of prostaglandin F2α, can cause ocular adverse events (AEs) associated with BAK. The purpose of this study was to evaluate the efficacy and safety of BAK-free latanoprost. A prospective, open-label, single-arm, multicenter, 8-week study in patients with primary open-angle glaucoma or ocular hypertension taking BAK-containing latanoprost for ≥12 months was performed. Patients were switched to BAK-free latanoprost ophthalmic solution 0.005% administered once daily, and eyes were assessed after 28 and 56 days. Primary efficacy and safety variables were TBUT and treatment-emergent AEs, respectively. At day 56, 40 eyes were evaluable. Mean TBUT increased significantly from baseline (3.67±1.60 seconds) to 5.03±2.64 and 6.06±3.39 seconds after 28 and 56 days of treatment with BAK-free latanoprost (P<0.0001). Ocular Surface Disease Index(©) (OSDI(©)) score also decreased significantly to 12.06±13.40 and 7.06±10.75 at 28 and 56 days, respectively, versus baseline (18.09±18.61, P<0.0001). In addition, inferior corneal staining score decreased significantly to 0.53 from baseline (0.85, P=0.0033). A reduction in conjunctival hyperemia and intraocular pressure was observed at both time points. No treatment-related serious AEs were evident and 12 (26.08%) treatment-emergent AEs occurred in seven patients, with eye pain and irritation being the most frequent. No clinically significant changes in vital signs or slit lamp examinations were observed. Results indicate that switching from BAK-containing latanoprost to BAK-free latanoprost resulted in significant improvements in TBUT, OSDI(©) score, and inferior corneal staining score, and measurable reductions in conjunctival hyperemia score. Furthermore, BAK-free latanoprost was well tolerated with only mild-to-moderate and self-limiting AEs. BAK-free latanoprost appears to be effective in protecting ocular surface integrity in glaucoma patients but further studies are needed to confirm this beneficial effect.

Anterior segment and external ocular disorders associated with HIV infections in the era of HAART in Chiang Mai University Hospital, a prospective descriptive cross sectional study.

PubMed

Singalavanija, Tassapol; Ausayakhun, Somsanguan; Tangmonkongvoragul, Chulaluck

2018-01-01

Human immunodeficiency virus (HIV) causes impairment to the human immune system which leads to immunocompromised conditions, including ocular complications. Several important HIV-associated disorders may involve the anterior segment, ocular surface, and adnexae organ such as dry eye, blepharitis which reduce quality of life of patients. In present, potent antiretroviral therapies HAART (highly active antiretroviral therapy) has improved the length and quality of life which may lead to an increased prevalence of anterior segment ocular disorders. Hence, this study has been undertaken to identify the prevalence and associated factors of anterior segment and external ocular disorder in HIV infected patients in the era of HAART. A prospective descriptive cross sectional study was carried out in HIV positive patients conducted at the Department of Ophthalmology, Chiang Mai University Hospital, from February 2014 to October 2015. Detail history and ocular examination was carried out to examine for anterior segment and external ocular disorders. A total number of 363 patients were included for this prospective cross-sectional study. From the total of 363 patients, 123 patients had an anterior segment and external ocular disorder which account as the prevalence of 33.9%. The most common anterior segment manifestations was dry eye seen in 36 patients (9.9%), followed by posterior blepharitis (Meibomian gland dysfunction) seen in 23 patients (6.3%) and anterior blepharitis seen in 12 patients (3.3%). Other ocular complications included microvasculopathy, immune recovery uveitis, conjunctivitis, papilloma, anterior uveitis, corneal ulcer, nevus, trichiasis, molluscum contangiosum, Kaposi sarcoma, interstitial keratitis, conjunctival lymphangiectasia, dacryocystitis, vernal keratoconjunctivitis and eyelid penicilosis. In this study, the prevalance of anterior segment disorders was higher than in the preHAART era. Dry eye, blepharitis and uveitis were the top three most common anterior segment disorders in the HAART era. The statistical analysis showed no association between age, sex, CD4 count, duration of infection or receiving HAART and anterior segment disorders. Anterior segment abnormalities reduce the quality of life of patients, so ophthalmologists have to be aware and complete ocular examination should be performed in all HIV infected patients.

Anterior segment and external ocular disorders associated with HIV infections in the era of HAART in Chiang Mai University Hospital, a prospective descriptive cross sectional study

PubMed Central

Ausayakhun, Somsanguan

2018-01-01

Human immunodeficiency virus (HIV) causes impairment to the human immune system which leads to immunocompromised conditions, including ocular complications. Several important HIV-associated disorders may involve the anterior segment, ocular surface, and adnexae organ such as dry eye, blepharitis which reduce quality of life of patients. In present, potent antiretroviral therapies HAART (highly active antiretroviral therapy) has improved the length and quality of life which may lead to an increased prevalence of anterior segment ocular disorders. Hence, this study has been undertaken to identify the prevalence and associated factors of anterior segment and external ocular disorder in HIV infected patients in the era of HAART. A prospective descriptive cross sectional study was carried out in HIV positive patients conducted at the Department of Ophthalmology, Chiang Mai University Hospital, from February 2014 to October 2015. Detail history and ocular examination was carried out to examine for anterior segment and external ocular disorders. A total number of 363 patients were included for this prospective cross-sectional study. From the total of 363 patients, 123 patients had an anterior segment and external ocular disorder which account as the prevalence of 33.9%. The most common anterior segment manifestations was dry eye seen in 36 patients (9.9%), followed by posterior blepharitis (Meibomian gland dysfunction) seen in 23 patients (6.3%) and anterior blepharitis seen in 12 patients (3.3%). Other ocular complications included microvasculopathy, immune recovery uveitis, conjunctivitis, papilloma, anterior uveitis, corneal ulcer, nevus, trichiasis, molluscum contangiosum, Kaposi sarcoma, interstitial keratitis, conjunctival lymphangiectasia, dacryocystitis, vernal keratoconjunctivitis and eyelid penicilosis. In this study, the prevalance of anterior segment disorders was higher than in the preHAART era. Dry eye, blepharitis and uveitis were the top three most common anterior segment disorders in the HAART era. The statistical analysis showed no association between age, sex, CD4 count, duration of infection or receiving HAART and anterior segment disorders. Anterior segment abnormalities reduce the quality of life of patients, so ophthalmologists have to be aware and complete ocular examination should be performed in all HIV infected patients. PMID:29466424

Electrically atomised formulations of timolol maleate for direct and on-demand ocular lens coatings.

PubMed

Mehta, Prina; Al-Kinani, Ali A; Haj-Ahmad, Rita; Arshad, Muhammad Sohail; Chang, Ming-Wei; Alany, Raid G; Ahmad, Zeeshan

2017-10-01

Advances in nanotechnology have enabled solutions for challenging drug delivery targets. While the eye presents numerous emerging opportunities for delivery, analysis and sensing; issues persist for conventional applications. This includes liquid phase formulation localisation on the ocular surface once administered as formulated eye-drops; with the vast majority of dosage (>90%) escaping from the administered site due to tear production and various drainage mechanisms. The work presented here demonstrates a single needle electrohydrodynamic (EHD) engineering process to nano-coat (as an on demand and controllable fiber depositing method) the surface of multiple contact lenses rendering formulations to be stationary on the lens and at the bio-interface. The coating process was operational based on ejected droplet charge and glaucoma drug timolol maleate (TM) was used to demonstrate surface coating optimisation, bio-surface permeation properties (flux, using a bovine model) and various kinetic models thereafter. Polymers PVP, PNIPAM and PVP:PNIPAM (50:50%w/w) were used to encapsulate the active. Nano-fibrous and particulate samples were characterised using SEM, FTIR, DSC and TGA to confirm structural and thermal stability of surface coated formulations. More than 52% of nano-structured coatings (for all formulations) were <200nm in diameter. In vitro studies show coatings to exhibit biphasic release profiles; an initial burst release followed by sustained release; with TM-loaded PNIPAM coating releasing most drug after 24h (89.8%). Kinetic modelling (Higuchi, Korsmeyer-Peppas) was indicative of quasi-Fickian diffusion whilst biological evaluation demonstrates adequate ocular tolerability. Results from permeation studies indicate coated lenses are ideal to reduce dosing regimen, which in turn will reduce systemic drug absorption. Florescent microscopy demonstrated probe and probe embedded coating behaviour from lens surface in vitro. The multiple lens surface coating method demonstrates sustained drug release yielding promising results; suggesting both novel device and method to enhance drug activity at the eyes surface which will reduce formulation drainage. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Intratumoral PV701 in Treating Patients With Advanced or Recurrent Unresectable Squamous Cell Carcinoma of the Head and Neck

ClinicalTrials.gov

2013-01-23

Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

Oral Rigosertib for Squamous Cell Carcinoma

ClinicalTrials.gov

2017-06-22

Head and Neck Squamous Cell Carcinoma; Anal Squamous Cell Carcinoma; Lung Squamous Cell Carcinoma; Cervical Squamous Cell Carcinoma; Esophageal Squamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Penile Squamous Cell Carcinoma

CEACAM1 is overexpressed in oral tumors and related to tumorigenesis.

PubMed

Wang, Fu-Fang; Guan, Bing-Xin; Yang, Jing-Yan; Wang, Hai-Tao; Zhou, Cheng-Jun

2017-03-01

Carcinoembryonic antigen-related adhesion molecule 1 (CEACAM1) is a type 1 transmembrane glycoprotein belonging to the CEA family, which has been known to exist as either soluble forms in body fluids or membrane-bound forms on the cell surface. Aberrant CEACAM1 expression is associated with tumorigenesis and has been reported in a variety of human tumors, especially malignancies. The aim of this study is to determine the expression of CEACAM1 in oral tumors, trying to study CEACAM1 different expressions as a function of histotype. CEACAM1 expression was observed by immunohistochemistry (IHC) with mouse anti-human antibody for CEACAM1. IHC was performed using avidin-biotin-diaminobenzidine staining. The results were expressed as average score ± SD (0 = negative/8 = highest) for each histotype. Oral tumors expressed more CEACAM1 than normal tissues including squamous and salivary epithelia (P < 0.05). In malignancies, the squamous cell carcinoma overexpressed CEACAM1, compared to well-differentiated squamous cell with more membranous expression; the intermediately and poorly differentiated squamous cell carcinoma showed more cytoplasmic expression (P < 0.05). In addition, the salivary tumors significantly expressed more CEACAM1 than squamous cell carcinoma (P < 0.05). So, we thought oral tumors overexpressed CEACAM1 and the cytoplasmic CEACAM1 might be involved in tumorigenesis, and also CEACAM1 might be regarded as a marker of salivary glandular tumors.

A Protective Eye Shield for Prevention of Media Opacities during Small Animal Ocular Imaging

PubMed Central

Bell, Brent A.; Kaul, Charles; Hollyfield, Joe G.

2014-01-01

Optical coherence tomography (OCT), scanning laser ophthalmoscopy (SLO) and other non-invasive imaging techniques are increasingly used in eye research to document disease-related changes in rodent eyes. Corneal dehydration is a major contributor to the formation of ocular opacities that can limit the repeated application of these techniques to individual animals. General anesthesia is usually required for imaging, which is accompanied by the loss of the blink reflex. As a consequence, the tear film cannot be maintained, drying occurs and the cornea becomes dehydrated. Without supplemental hydration, structural damage to the cornea quickly follows. Soon thereafter, anterior lens opacities can also develop. Collectively these changes ultimately compromise image quality, especially for studies involving repeated use of the same animal over several weeks or months. To minimize these changes, a protective shield was designed for mice and rats that prevent ocular dehydration during anesthesia. The eye shield, along with a semi-viscous ophthalmic solution, is placed over the corneas as soon as the anesthesia immobilizes the animal. Eye shields are removed for only the brief periods required for imaging and then reapplied before the fellow eye is examined. As a result, the corneal surface of each eye is exposed only for the time required for imaging. The device and detailed methods described here minimize the corneal and lens changes associated with ocular surface desiccation. When these methods are used consistently, high quality images can be obtained repeatedly from individual animals. PMID:25245081

Tear Film Osmolarity in Subjects with Acute Allergic Rhinoconjunctivitis

PubMed Central

NITODA, EIRINI; LAVARIS, ANASTASIOS; LAIOS, KONSTANTINOS; ANDROUDI, SOPHIA; KALOGEROPOULOS, CHRIS D; TSATSOS, MICHAEL; DAMASKOS, CHRISTOS; GARMPIS, NIKOLAOS; MOSCHOS, MARILITA M

2018-01-01

Background/Aim: Acute allergic rhinoconjuctivitis is the most common form of ocular allergies. The pathogenetic mechanisms are based on an immunoglobulin E (IgE)-mediated hypersensitivity reaction. On the other hand, tear osmolarity has been suggested to be an index of ocular surface damage and inflammation. These data were the motive to investigate the levels of tear osmolarity in subjects with acute allergic rhinoconjuctivitis, before and after administration of artificial tears. Patients and Methods: Forty-five subjects with acute allergic rhinoconjuctivitis were randomly divided into three groups, based on the type of artificial tears that they received: Group A (Thera tears), Group B (Wet therapy) and Group C (Tears Naturale free). The eye drops were administered six times a day for 60 days and all subjects underwent grading of subjective symptoms and clinical examination at baseline and at the end of the treatment. Results: The diagnosis of severe eye disease, which was based on ocular surface disease index (OSDI; Allergan, Inc, Irvine, CA, USA) and tear osmolarity values, concerned all patients at baseline. Although the administration of artificial tears significantly ameliorated the symptoms and the ocular variables in all groups, the results were better in the first group. Tear osmolarity was strongly and negatively correlated with tear film breakup time (BUT) and Schirmer I test at 2 months. Contrariwise, symptoms were eliminated, when tear osmolarity was decreased. Conclusion: Acute allergic rhinoconjuctivitis is characterized by tear hyperosmolarity, which can be rehabilitated with the administration of hypotonic artificial tears. PMID:29475928

Impact of Chemical Structure on Conjunctival Drug Permeability: Adopting Porcine Conjunctiva and Cassette Dosing for Construction of In Silico Model.

PubMed

Ramsay, Eva; Ruponen, Marika; Picardat, Théo; Tengvall, Unni; Tuomainen, Marjo; Auriola, Seppo; Toropainen, Elisa; Urtti, Arto; Del Amo, Eva M

2017-09-01

Conjunctiva occupies most of the ocular surface area, and conjunctival permeability affects ocular and systemic drug absorption of topical ocular medications. Therefore, the aim of this study was to obtain a computational in silico model for structure-based prediction of conjunctival drug permeability. This was done by employing cassette dosing and quantitative structure-property relationship (QSPR) approach. Permeability studies were performed ex vivo across fresh porcine conjunctiva and simultaneous dosing of a cassette mixture composed of 32 clinically relevant drug molecules with wide chemical space. The apparent permeability values were obtained using drug concentrations that were quantified with liquid chromatography tandem-mass spectrometry. The experimental data were utilized for building a QSPR model for conjunctival permeability predictions. The conjunctival permeability values presented a 17-fold range (0.63-10.74 × 10 -6 cm/s). The final QSPR had a Q 2 value of 0.62 and predicted the external test set with a mean fold error of 1.34. The polar surface area, hydrogen bond donor, and halogen ratio were the most relevant descriptors for defining conjunctival permeability. This work presents for the first time a predictive QSPR model of conjunctival drug permeability and a comprehensive description on conjunctival isolation from the porcine eye. The model can be used for developing new ocular drugs. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Influence of Ophthalmic Solutions on Tear Components.

PubMed

Shigeyasu, Chika; Yamada, Masakazu; Akune, Yoko

2016-11-01

Tear fluids are a mixture of secretions derived from lacrimal glands, accessory lacrimal glands, conjunctiva, and meibomian glands. Compositional changes to tears occur in the normal state and during ocular surface disease, such as dry eye conditions. We have investigated compositional changes to tears after topical application of ophthalmic solutions, with regard to tear-specific proteins (secretory immunoglobulin A, lactoferrin, lipocalin-1, and lysozyme) and ocular surface mucin in normal and dry eye conditions using high-performance liquid chromatography. After application of saline solution (0.9% sodium chloride) in normal subjects, transient but significant decreases in all tear components were observed. The recovery of protein concentrations took up to 30 minutes and lasted longer when the saline solution was applied more frequently. When applying ophthalmic solutions, a balance between washout and dilutional effects should be considered in addition to the therapeutic effect. Investigation of the effect of diquafosol solution (3%) in normal subjects revealed a significant increase in sialic acid concentration, a marker of ocular mucin, at 5 minutes after application, whereas a significant decrease was observed with saline. This result indicates the accelerated secretion of mucin from ocular tissues induced by diquafosol. A clinical study to determine the efficacy of diquafosol in patients with dry eye revealed improvements in tear breakup time, keratoconjunctival staining scores, and Schirmer test score, accompanied by an increase in sialic acid concentration in tears. Investigating normal and dry eye conditions through tear analysis may clarify the pathophysiology of dry eye conditions and support the efficacy of treatments.

Effects of vitamin D receptor knockout on cornea epithelium gap junctions.

PubMed

Lu, Xiaowen; Watsky, Mitchell A

2014-05-06

Gap junctions are present in all corneal cell types and have been shown to have a critical role in cell phenotype determination. Vitamin D has been shown to influence cell differentiation, and recent work demonstrates the presence of vitamin D in the ocular anterior segment. This study measured and compared gap junction diffusion coefficients among different cornea epithelium phenotypes and in keratocytes using a noninvasive technique, fluorescence recovery after photobleaching (FRAP), and examined the influence of vitamin D receptor (VDR) knockout on epithelial gap junction communication in intact corneas. Previous gap junction studies in cornea epithelium and keratocytes were performed using cultured cells or ex vivo invasive techniques. These invasive techniques were unable to measure diffusion coefficients and likely were disruptive to normal cell physiology. Corneas from VDR knockout and control mice were stained with 5(6)-carboxyfluorescein diacetate (CFDA). Gap junction diffusion coefficients of the corneal epithelium phenotypes and of keratocytes, residing in intact corneas, were detected using FRAP. Diffusion coefficients equaled 18.7, 9.8, 5.6, and 4.2 μm(2)/s for superficial squamous cells, middle wing cells, basal cells, and keratocytes, respectively. Corneal thickness, superficial cell size, and the superficial squamous cell diffusion coefficient of 10-week-old VDR knockout mice were significantly lower than those of control mice (P < 0.01). The superficial cell diffusion coefficient of heterozygous mice was significantly lower than control mice (P < 0.05). Our results demonstrate differences in gap junction dye spread among the epithelial cell phenotypes, mirroring the epithelial developmental axis. The VDR knockout influences previously unreported cell-to-cell communication in superficial epithelium.

Soy Isoflavones in Preventing Head and Neck Cancer Recurrence in Patients With Stage I-IV Head and Neck Cancer Undergoing Surgery

ClinicalTrials.gov

2016-09-01

Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Stage I Hypopharyngeal Squamous Cell Carcinoma; Stage I Laryngeal Squamous Cell Carcinoma; Stage I Laryngeal Verrucous Carcinoma; Stage I Lip and Oral Cavity Squamous Cell Carcinoma; Stage I Oral Cavity Verrucous Carcinoma; Stage I Oropharyngeal Squamous Cell Carcinoma; Stage II Hypopharyngeal Squamous Cell Carcinoma; Stage II Laryngeal Squamous Cell Carcinoma; Stage II Laryngeal Verrucous Carcinoma; Stage II Lip and Oral Cavity Squamous Cell Carcinoma; Stage II Oral Cavity Verrucous Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Laryngeal Verrucous Carcinoma; Stage III Lip and Oral Cavity Squamous Cell Carcinoma; Stage III Oral Cavity Verrucous Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma

Sorafenib Tosylate, Cisplatin, and Docetaxel in Treating Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

ClinicalTrials.gov

2018-05-22

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Apoptosis of conjunctival epithelial cells before and after the application of autologous serum eye drops in severe dry eye disease.

PubMed

Rybickova, Ivana; Vesela, Viera; Fales, Ivan; Skalicka, Pavlina; Jirsova, Katerina

2016-06-01

To assess the impact of autologous serum eye drops on the level of ocular surface apoptosis in patients with bilateral severe dry eye disease. This prospective study was conducted on 10 patients with severe dry eye due to graft versus host disease (group 1) and 6 patients with severe dry eye due to primary Sjögren's syndrome (group 2). Impression cytology specimens from the bulbar conjunctiva were obtained before and after a three-month treatment with 20% autologous serum eye drops applied a maximum of 12 times a day together with regular therapy with artificial tears. The percentage of apoptotic epithelial cells was evaluated immunochemically using anti-active caspase 3 antibody. In group 1, the mean percentage of apoptotic cells was 3.6% before the treatment. The three-month treatment led to a significant decrease to a mean percentage of 1.8% (P = 0.028). The mean percentage of apoptotic conjunctival cells decreased from 5.4% before the treatment to 3.8% in group 2; however, these results did not reach the level of significance. Three-month autologous serum treatment led to the improvement of ocular surface apoptosis, especially in the group of patients with severe dry eye due to graft versus host disease. This result supports the very positive effect of autologous serum on the ocular surface in patients suffering from severe dry eye.

EFFECT OF INFLAMMATION ON LACRIMAL GLAND FUNCTION

PubMed Central

Zoukhri, Driss

2005-01-01

The lacrimal gland is the main contributor to the aqueous layer of the tear film. It secretes proteins, electrolytes and water, which helps to nourish and protect the ocular surface. Lacrimal gland secretion is primarily under neural control, which is achieved through a neural reflex arc. Stimuli to the ocular surface activate afferent sensory nerves in the cornea and conjunctiva. This in turn activates efferent parasympathetic and sympathetic nerves in the lacrimal gland to stimulate secretion. Sex steroid hormones are also important regulators of lacrimal gland functions. A decrease or lack of lacrimal gland secretion is the leading cause of aqueous tear deficient dry eye syndrome (DES). It has been suggested that DES is an inflammatory disorder that affects the ocular surface and the lacrimal gland. In several pathological instances, the lacrimal gland can become a target of the immune system and show signs of inflammation. This can result from autoimmune diseases (Sjögren's syndrome), organ transplantation (graft versus host disease), or simply as a result of aging. The hallmarks of lacrimal gland inflammation are the presence of focal lymphocytic infiltrates and increased production of proinflammatory cytokines. The mechanisms leading to lacrimal gland dysfunction are still poorly understood. Apoptosis, production of autoantibodies, hormonal imbalance, alterations in signaling molecules, neural dysfunction, and increased levels of proinflammatory cytokines have been proposed as possible mediators of lacrimal gland insufficiency in disease states. PMID:16309672

Effects of environment pollution on the ocular surface.

PubMed

Jung, Se Ji; Mehta, Jodhbir S; Tong, Louis

2018-04-01

The twenty-first century is fraught with dangers like climate change and pollution, which impacts human health and mortality. As levels of pollution increase, respiratory illnesses and cardiovascular ailments become more prevalent. Less understood are the eye-related complaints, which are commonly associated with increasing pollution. Affected people may complain of irritation, redness, foreign body sensation, tearing, and blurring of vision. Sources of pollution are varied, ranging from gases (such as ozone and NO 2 ) and particulate matter produced from traffic, to some other hazards associated with indoor environments. Mechanisms causing ocular surface disease involve toxicity, oxidative stress, and inflammation. Homeostatic mechanisms of the ocular surface may adapt to certain chronic changes in the environment, so affected people may not always be symptomatic. However there are many challenges associated with assessing effects of air pollution on eyes, as pollution is large scale and difficult to control. Persons with chronic allergic or atopic tendencies may have a pre-existing state of heightened mucosal immune response, hence they may have less tolerance for further environmental antigenic stimulation. It is beneficial to identify vulnerable people whose quality of life will be significantly impaired by environmental changes and provide counter measures in the form of protection or treatment. Better technologies in monitoring of pollutants and assessment of the eye will facilitate progress in this field. Copyright © 2018 Elsevier Inc. All rights reserved.

Management of Corneal Scarring Secondary to Herpes Zoster Keratitis.

PubMed

Hassan, Omar M; Farooq, Asim V; Soin, Ketki; Djalilian, Ali R; Hou, Joshua H

2017-08-01

To review the management of visually significant corneal scarring secondary to herpes zoster keratitis (HZK). Literature review. Management options for visually significant corneal scarring secondary to HZK include scleral contact lenses, photorefractive or phototherapeutic keratectomy, lamellar keratoplasty, penetrating keratoplasty, and keratoprosthesis. Many authors recommend tarsorrhaphy in at-risk patients at the time of corneal transplantation. Most published studies either did not mention or did not use systemic antivirals at the time of surgery. Longer quiescent periods before surgical intervention may be associated with increased rates of graft survival. Reports of HZK recurrence after live-attenuated vaccine administration suggest that risks and benefits of the vaccine should be carefully considered. Overall, the prognosis of surgical intervention for corneal scarring due to HZK relies on appropriate patient selection and measures to ensure ocular surface stability. There remains a serious risk of ocular surface instability and corneal melt in these patients. Unfortunately, there is a lack of prospective studies in this area to guide clinical management. Patients with visually significant corneal scarring secondary to HZK may have good outcomes with the appropriate medical and surgical considerations, particularly in the absence of active ocular surface disease and inflammation. Those with active disease may benefit from delaying surgical intervention until a satisfactory quiescent period has been achieved. Prospective studies, such as the proposed Zoster Eye Disease Study, are imperative for validating these principles and determining evidence-based management guidelines.

Effects of DA-6034, a flavonoid derivative, on mucin-like glycoprotein and ocular surface integrity in a rabbit model.

PubMed

Choi, Seul Min; Seo, Mi Jeong; Lee, Yeong Geon; Lee, Min Jung; Jeon, Hyung Jun; Kang, Kyung Koo; Ahn, Byoung Ok; Yoo, Moohi

2009-01-01

This study was designed to assess whether DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone monohydrate), a new synthetic derivative of eupatilin, increases secretion of mucin-like glycoprotein and some mucins species in conjunctiva and cornea, and contributes to the preservation of ocular surface integrity. Human conjunctival and corneal epithelial cells were incubated with DA-6034 (1-250 microM). To investigate mucin secreting activity more directly, isolated rat conjunctival goblet cells were also used. Corneal protection was investigated using a desiccation-induced rabbit model of dry eye syndrome. It was found that DA-6034 increased mucin-like glycoprotein levels of both conjunctival and corneal epithelial cells at concentrations above 100 microM. Using human conjunctival epithelial cells, it was demonstrated that treatment with DA-6034 (200 microM) significantly increased production of some mucins species including MUC1, MUC2, MUC4, MUC5AC, MUC5B, and MUC16. DA-6034 also significantly increased MUC5AC production from conjunctival goblet cells isolated from rats. In the rabbit desiccation model, an ophthalmic suspension containing 3% DA-6034 significantly reduced corneal damage induced by desiccation. These results suggest that DA-6034 is a good candidate for treatment of dry eye through maintaining ocular surface integrity, which might be related to mucin secretion.

Effect of chitosan-N-acetylcysteine conjugate in a mouse model of botulinum toxin B-induced dry eye.

PubMed

Hongyok, Teeravee; Chae, Jemin J; Shin, Young Joo; Na, Daero; Li, Li; Chuck, Roy S

2009-04-01

To evaluate the effect of a thiolated polymer lubricant, chitosan-N-acetylcysteine conjugate (C-NAC), in a mouse model of dry eye. Eye drops containing 0.5% C-NAC, 0.3% C-NAC, a vehicle (control group), artificial tears, or fluorometholone were applied in a masked fashion in a mouse model of induced dry eye from 3 days to 4 weeks after botulinum toxin B injection. Corneal fluorescein staining was periodically recorded. Real-time reverse transcriptase-polymerase chain reaction and immunofluorescence staining were performed at the end of the study to evaluate inflammatory cytokine expressions. Mice treated with C-NAC, 0.5%, and fluorometholone showed a downward trend that was not statistically significant in corneal staining compared with the other groups. Chitosan-NAC formulations, fluorometholone, and artificial tears significantly decreased IL-1beta (interleukin 1beta), IL-10, IL-12alpha, and tumor necrosis factor alpha expression in ocular surface tissues. The botulinum toxin B-induced dry eye mouse model is potentially useful in evaluating new dry eye treatment. Evaluation of important molecular biomarkers suggests that C-NAC may impart some protective ocular surface properties. However, clinical data did not indicate statistically significant improvement of tear production and corneal staining in any of the groups tested. Topically applied C-NAC might protect the ocular surface in dry eye syndrome, as evidenced by decreased inflammatory cytokine expression.

Durvalumab Before Surgery in Treating Patients With Oral Cavity or Oropharynx Cancer

ClinicalTrials.gov

2017-12-20

Human Papillomavirus Infection; Stage I Oral Cavity Squamous Cell Carcinoma; Stage I Oropharyngeal Squamous Cell Carcinoma; Stage II Oral Cavity Squamous Cell Carcinoma; Stage II Oropharyngeal Squamous Cell Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma

Temsirolimus With or Without Cetuximab in Patients With Recurrent and/or Metastatic Head and Neck Cancer Who Did Not Respond to Previous Therapy

ClinicalTrials.gov

2017-02-23

Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Major Salivary Gland Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Major Salivary Gland Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Major Salivary Gland Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma

Ocular volumetry using fast high-resolution MRI during visual fixation.

PubMed

Tanitame, K; Sone, T; Miyoshi, T; Tanitame, N; Otani, K; Akiyama, Y; Takasu, M; Date, S; Kiuchi, Y; Awai, K

2013-04-01

Volumetry may be useful for evaluating treatment response and prognosis of intraocular lesions. Phantom, volunteer, and patient studies were performed to determine whether ocular MR volumetry is reproducible. Half-Fourier single-shot RARE and FSPGR sequences at 1.5T with a 76-mm-diameter surface coil were optimized to obtain still ocular images. Volumetry accuracies of each sequence were compared with simulated subretinal phantom volumes. Ocular volumetry was performed in 15 volunteers twice in 1 week by using contiguous axial images of the globes while the subjects stared at a target, and images were acquired in 2 seconds before the subjects were instructed to blink, with this process repeated as necessary. Imaging, intraobserver, and interobserver reproducibility for volumes of the whole eyeball and anterior chamber were assessed. Ocular volumetry was also performed in 6 patients with intraocular tumors before and after treatment. The phantom study demonstrated that measurement error rates with RARE were significantly lower than with FSPGR (P<.01). The volunteer study demonstrated excellent imaging and intraobserver reproducibility of RARE volumetry for whole eyeballs and anterior chambers (P<.01). Although no interobserver differences were observed in anterior chamber volume measurement (P=.33), there was a significant difference between the 2 observers in eyeball volume measurement (P<.01). Follow-up volumetric data were useful for treatment decisions in all patients. Ocular volumetry from contiguous ultrafast RARE images obtained during visual fixation is feasible in volunteer and patient studies and is superior to FSPGR images.

Characterization of the corneal surface in limbal stem cell deficiency and after transplantation of cultured allogeneic limbal epithelial cells.

PubMed

Chen, Peng; Zhou, Qingjun; Wang, Junyi; Zhao, Xiaowen; Duan, Haoyun; Wang, Yao; Liu, Ting; Xie, Lixin

2016-09-01

The objective of this study was to characterize the changes that occur in the cornea during Limbal Stem Cell Deficiency (LSCD) and on the corneal surface after transplantation of ex vivo cultured allogeneic limbal epithelial transplantation (CALET). Forty-one pannus were analyzed to characterize the changes found in the cornea in LSCD. Nineteen impression cytology samples, including 14 pannus and five corneal buttons, obtained during subsequent procedures from patients who had undergone CALET were examined to assess the effect of CALET and to determine the long-term fate of donor cells. The presence of donor and recipient epithelial cells in each sample was determined by short tandem repeat (STR) amplification and fluorescent-multiplex polymerase chain reaction (PCR). Phenotypic analysis of the epithelium was performed by immunohistochemistry and real-time PCR. The expression of lineage markers was similar between pannus and conjunctivae, but not to corneas. Objective long-term benefits from the transplantation were recorded in most cases. After CALET, the lineage markers in the excised corneal buttons and pannus showed a limbus phenotype. DNA analysis of the 19 cases showed no donor cells present on the ocular surface beyond three months after CALET. LSCD was characterized by ingrowth of abnormal, inflamed tissue with a conjunctival phenotype. CALET was a useful technique for restoring the ocular surface in LSCD. However, such benefits did not necessarily correlate with survival of measurable numbers of donor cells on the ocular surface. The absence of donor DNA beyond three months raises questions regarding the period of ongoing immunosuppression and the origin of the regenerated corneal epithelium.

Sunitinib, Cetuximab, and Radiation Therapy in Treating Patients With Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck

ClinicalTrials.gov

2013-07-01

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Salivary Gland Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Application of erbium: YAG laser in ocular ablation.

PubMed

Tsubota, K

1990-01-01

Recent developments in lasers have provided us the possibility of laser ocular surgery. The xenon, argon, neodymium:YAG and dye lasers have been successfully used in out-patient clinics. The excimer laser has been attracting researchers' interest in the new application of laser to cornea and lens. The erbium:YAG laser emits a 2.94-microns beam that can ablate the transparent ocular tissues such as lenses and corneas. The author has applied this laser to the cornea, lens, vitreous and other ocular tissues. The erbium:YAG laser beam was directed through a 1.5-meter-long, 200-microns-diameter fiberoptic guide. The radiant energy measured about 50 mJ at the end of the probe. The laser was emitted as a 400-microsecond pulse. Freshly enucleated rabbit eyes were used in this study. Laser burns were applied to the tissue surface at various energy settings. At minimal power, the tissues were coagulated by the erbium:YAG laser application. At a power of more than 636-954 mJ/mm2, tissue began to evaporate; the tissue loss was observed under a surgical light microscope. Corneal photoablation, lens ablation, iridotomy, trabeculotomy, cutting of the vitreous and retinal ablation were easily performed. Like the excimer laser, the erbium:YAG laser is a potential tool for ocular surgery.

Phase II Randomized Trial of the Combination of Cetuximab and Sorafenib or Single Agent Cetuximab

ClinicalTrials.gov

2017-12-28

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Entolimod in Treating Patients With Stage III-IV Squamous Cell Head and Neck Cancer Receiving Cisplatin and Radiation Therapy

ClinicalTrials.gov

2013-12-10

Mucositis; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Cisplatin With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

ClinicalTrials.gov

2017-03-22

Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Squamous Cell Carcinoma; Stage IVB Laryngeal Verrucous Carcinoma; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVB Oral Cavity Verrucous Carcinoma; Stage IVB Oropharyngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Squamous Cell Carcinoma; Stage IVC Laryngeal Verrucous Carcinoma; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Stage IVC Oral Cavity Verrucous Carcinoma; Stage IVC Oropharyngeal Squamous Cell Carcinoma; Tongue Carcinoma

Erlotinib in Treating Patients With Advanced Non-Small Cell Lung Cancer, Ovarian Cancer, or Squamous Cell Carcinoma of the Head and Neck

ClinicalTrials.gov

2013-01-08

Recurrent Non-small Cell Lung Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IV Non-small Cell Lung Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx

Nasal Colonisation by Staphylococcus aureus Depends upon Clumping Factor B Binding to the Squamous Epithelial Cell Envelope Protein Loricrin

PubMed Central

Mulcahy, Michelle E.; Geoghegan, Joan A.; Monk, Ian R.; O'Keeffe, Kate M.; Walsh, Evelyn J.

2012-01-01

Staphylococcus aureus asymptomatically colonises the anterior nares, but the host and bacterial factors that facilitate colonisation remain incompletely understood. The S. aureus surface protein ClfB has been shown to mediate adherence to squamous epithelial cells in vitro and to promote nasal colonisation in both mice and humans. Here, we demonstrate that the squamous epithelial cell envelope protein loricrin represents the major target ligand for ClfB during S. aureus nasal colonisation. In vitro adherence assays indicated that bacteria expressing ClfB bound loricrin most likely by the “dock, lock and latch” mechanism. Using surface plasmon resonance we showed that ClfB bound cytokeratin 10 (K10), a structural protein of squamous epithelial cells, and loricrin with similar affinities that were in the low µM range. Loricrin is composed of three separate regions comprising GS-rich omega loops. Each loop was expressed separately and found to bind ClfB, However region 2 bound with highest affinity. To investigate if the specific interaction between ClfB and loricrin was sufficient to facilitate S. aureus nasal colonisation, we compared the ability of ClfB+ S. aureus to colonise the nares of wild-type and loricrin-deficient (Lor−/−) mice. In the absence of loricrin, S. aureus nasal colonisation was significantly impaired. Furthermore a ClfB− mutant colonised wild-type mice less efficiently than the parental ClfB+ strain whereas a similar lower level of colonisation was observed with both the parental strain and the ClfB− mutant in the Lor−/− mice. The ability of ClfB to support nasal colonisation by binding loricrin in vivo was confirmed by the ability of Lactococcus lactis expressing ClfB to be retained in the nares of WT mice but not in the Lor−/− mice. By combining in vitro biochemical analysis with animal model studies we have identified the squamous epithelial cell envelope protein loricrin as the target ligand for ClfB during nasal colonisation by S. aureus. PMID:23300445

Talactoferrin in Treating Patients With Relapsed or Refractory Non-Small Cell Lung Cancer or Squamous Cell Head and Neck Cancer

ClinicalTrials.gov

2016-07-30

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Non-small Cell Lung Cancer; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Topical administration of interleukin-1 receptor antagonist as a therapy for aqueous-deficient dry eye in autoimmune disease.

PubMed

Vijmasi, Trinka; Chen, Feeling Y T; Chen, Ying Ting; Gallup, Marianne; McNamara, Nancy

2013-01-01

Dry eye is commonly associated with autoimmune diseases such as Sjögren's syndrome (SS), in which exocrinopathy of the lacrimal gland leads to aqueous tear deficiency and keratoconjunctivitis sicca (KCS). KCS is among the most common and debilitating clinical manifestations of SS that is often recalcitrant to therapy. We established mice deficient in the autoimmune regulator (Aire) gene as a model for autoimmune-mediated aqueous-deficient dry eye. In Aire-deficient mice, CD4+ T cells represent the main effector cells and local signaling via the interleukin-1 (IL-1/IL-1R1) pathway provides an essential link between autoreactive CD4+ T cells and ocular surface disease. In the current study, we evaluated the efficacy of topical administration of IL-1R1 antagonist (IL-1RA) anakinra in alleviating ocular surface damage resulting from aqueous-deficient dry eye in the setting of autoimmune disease. We compared the effect of commercially available IL-1R1 antagonist, anakinra (50 μg/mL concentration) to that of carboxymethylcellulose (CMC) vehicle control as a treatment for dry eye. Age-matched, Aire-deficient mice were treated three times daily with anakinra or CMC vehicle for 14 days using side-by-side (n = 4 mice/group) and paired-eye (n = 5) comparisons. We assessed (1) ocular surface damage with lissamine green staining; (2) tear secretion with wetting of phenol-red threads; (3) goblet cell (GC) mucin glycosylation with lectin histochemistry; (4) immune cell infiltration using anti-F4/80, CD11c, and CD4 T cell antibodies; and (5) gene expression of cornified envelope protein, Small Proline-Rich Protein-1B (SPRR1B) with real-time quantitative polymerase chain reaction. Aire-deficient mice treated with anakinra experienced significant improvements in ocular surface integrity and tear secretion. After 7 days of treatment, lissamine green staining decreased in eyes treated with anakinra compared to an equivalent increase in staining following treatment with CMC vehicle alone. By day 14, lissamine green staining in anakinra-treated eyes remained stable while eyes treated with CMC vehicle continued to worsen. Accordingly, there was a progressive decline in tear secretion in eyes treated with the CMC vehicle compared to a progressive increase in the anakinra-treated eyes over the 2-week treatment period. Aberrant acidification of GC mucins and pathological keratinization of the ocular surface were significantly reduced in anakinra-treated eyes. Significantly fewer Maackia amurensis leukoagglutinin positive goblet cells were noted in the conjunctiva of anakinra-treated eyes with a corresponding decrease in the expression of the pathological keratinization marker, SPRR1B. Finally, there was a downward trend in the infiltration of each immune cell type following anakinra treatment, but the cell counts compared to eyes treated with the vehicle alone were not significantly different. IL-1R antagonist, anakinra, demonstrates therapeutic benefits as a topical treatment for aqueous-deficient dry eye in a spontaneous mouse model of autoimmune KCS that mimics the clinical characteristics of SS. Targeting the IL-1/IL-1R1 signaling pathway through topical administration of IL-1RA may provide a novel option to improve ocular surface integrity, increase tear secretion, and restore the normal glycosylation pattern of GC mucins in patients with SS.

Topical administration of interleukin-1 receptor antagonist as a therapy for aqueous-deficient dry eye in autoimmune disease

PubMed Central

Vijmasi, Trinka; Chen, Feeling YT; Chen, Ying Ting; Gallup, Marianne

2013-01-01

Purpose Dry eye is commonly associated with autoimmune diseases such as Sjögren’s syndrome (SS), in which exocrinopathy of the lacrimal gland leads to aqueous tear deficiency and keratoconjunctivitis sicca (KCS). KCS is among the most common and debilitating clinical manifestations of SS that is often recalcitrant to therapy. We established mice deficient in the autoimmune regulator (Aire) gene as a model for autoimmune-mediated aqueous-deficient dry eye. In Aire-deficient mice, CD4+ T cells represent the main effector cells and local signaling via the interleukin-1 (IL-1/IL-1R1) pathway provides an essential link between autoreactive CD4+ T cells and ocular surface disease. In the current study, we evaluated the efficacy of topical administration of IL-1R1 antagonist (IL-1RA) anakinra in alleviating ocular surface damage resulting from aqueous-deficient dry eye in the setting of autoimmune disease. Methods We compared the effect of commercially available IL-1R1 antagonist, anakinra (50 μg/mL concentration) to that of carboxymethylcellulose (CMC) vehicle control as a treatment for dry eye. Age-matched, Aire-deficient mice were treated three times daily with anakinra or CMC vehicle for 14 days using side-by-side (n=4 mice/group) and paired-eye (n=5) comparisons. We assessed (1) ocular surface damage with lissamine green staining; (2) tear secretion with wetting of phenol-red threads; (3) goblet cell (GC) mucin glycosylation with lectin histochemistry; (4) immune cell infiltration using anti-F4/80, CD11c, and CD4 T cell antibodies; and (5) gene expression of cornified envelope protein, Small Proline-Rich Protein-1B (SPRR1B) with real-time quantitative polymerase chain reaction. Results Aire-deficient mice treated with anakinra experienced significant improvements in ocular surface integrity and tear secretion. After 7 days of treatment, lissamine green staining decreased in eyes treated with anakinra compared to an equivalent increase in staining following treatment with CMC vehicle alone. By day 14, lissamine green staining in anakinra-treated eyes remained stable while eyes treated with CMC vehicle continued to worsen. Accordingly, there was a progressive decline in tear secretion in eyes treated with the CMC vehicle compared to a progressive increase in the anakinra-treated eyes over the 2-week treatment period. Aberrant acidification of GC mucins and pathological keratinization of the ocular surface were significantly reduced in anakinra-treated eyes. Significantly fewer Maackia amurensis leukoagglutinin positive goblet cells were noted in the conjunctiva of anakinra-treated eyes with a corresponding decrease in the expression of the pathological keratinization marker, SPRR1B. Finally, there was a downward trend in the infiltration of each immune cell type following anakinra treatment, but the cell counts compared to eyes treated with the vehicle alone were not significantly different. Conclusions IL-1R antagonist, anakinra, demonstrates therapeutic benefits as a topical treatment for aqueous-deficient dry eye in a spontaneous mouse model of autoimmune KCS that mimics the clinical characteristics of SS. Targeting the IL-1/IL-1R1 signaling pathway through topical administration of IL-1RA may provide a novel option to improve ocular surface integrity, increase tear secretion, and restore the normal glycosylation pattern of GC mucins in patients with SS. PMID:24068863

PI3K Inhibitor BKM120 and Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

ClinicalTrials.gov

2017-05-22

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Salivary Gland Squamous Cell Carcinoma; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Optimization and physicochemical characterization of a triamcinolone acetonide-loaded NLC for ocular antiangiogenic applications.

PubMed

Araújo, J; Gonzalez-Mira, E; Egea, M A; Garcia, M L; Souto, E B

2010-06-30

The purpose of this study was to develop a novel nanostructured lipid carrier (NLC) for the intravitreal-targeting delivery of triamcinolone acetonide (TA) by direct ocular instillation. A five-level central composite rotable design was used to study the influence of four different variables on the physicochemical characteristics of NLCs. The analysis of variance (ANOVA) statistical test was used to assess the optimization of NLC production parameters. The systems were produced by high pressure homogenization using Precirol ATO5 and squalene as solid and liquid lipids respectively, and Lutrol F68 as surfactant. Homogenization at 600 bar for 3 cycles of the optimized formulation resulted in the production of small NLC (mean diameter < 200 nm) with a homogeneous particle size distribution (polydispersity index (PI) approximately 0.1), of negatively charged surface (approximately |45| mV) and high entrapment efficiency (approximately 95%). Surface morphology was assessed by SEM which revealed fairly spherical shape. DSC, WAXS and FT-IR analyses confirmed that TA was mostly entrapped into the NLC, characterized by an amorphous matrix. In vivo Draize test showed no signs of ocular toxicity. 2010 Elsevier B.V. All rights reserved.

How Ocular Surface Disease Impacts the Glaucoma Treatment Outcome

PubMed Central

Kaštelan, Snježana; Tomić, Martina; Metež Soldo, Kata; Salopek-Rabatić, Jasminka

2013-01-01

The treatment goals for glaucoma are lowering the intraocular pressure and preservation of vision. Topical hypotensive drops are the standard form of therapy which is often associated with some symptoms of toxicity, ocular inflammation, allergy, or ocular surface disease (OSD). OSD is a common comorbidity in glaucoma patients, and its prevalence with glaucoma increases with age. Use of topical treatment could additionally increase symptoms of OSD mostly due to preservatives added to multidose medication bottles used to reduce the risk of microbial contamination. This toxicity has been particularly associated with BAK, the most commonly used preservative which damages conjunctival and corneal epithelial cells and significantly aggravates OSD symptoms. OSD adversely affects patients' quality of life causing discomfort and problems with vision which in turn may result in noncompliance, lack of adherence, and eventually visual impairment. In the management of glaucoma patients OSD symptoms should not be overlooked. If they are present, topical glaucoma treatment should be adapted by decreasing the amount of drops instilled daily, using BAK-free or preservative-free medication and lubricants if necessary. Awareness of the presence and importance of OSD will in turn improve patients' adherence and compliance and thus ultimately the preservation of long-term vision. PMID:24224176

Poly(amidoamine) dendrimers as ophthalmic vehicles for ocular delivery of pilocarpine nitrate and tropicamide.

PubMed

Vandamme, Th F; Brobeck, L

2005-01-20

The purpose of this study was to determine the influence of a controlled incremental increase in size, molecular weight and number of amine, carboxylate and hydroxyl surface groups in several series of poly(amidoamine) (PAMAM) dendrimers for controlled ocular drug delivery. The duration of residence time was evaluated after solubilization of several series of PAMAM dendrimers (generations 1.5 and 2-3.5 and 4) in buffered phosphate solutions containing 2 per thousand (w/v) of fluorescein. The New Zealand albino rabbit was used as an in vivo model for qualitative and quantitative assessment of ocular tolerance and retention time after a single application of 25 microl of dendrimer solution to the eye. The same model was also used to determine the prolonged miotic or mydriatic activities of dendrimer solutions, some containing pilocarpine nitrate and some tropicamide, respectively. Residence time was longer for the solutions containing dendrimers with carboxylic and hydroxyl surface groups. No prolongation of remanence time was observed when dendrimer concentration (0.25-2%) increased. The remanence time of PAMAM dendrimer solutions on the cornea showed size and molecular weight dependency. This study allowed novel macromolecular carriers to be designed with prolonged drug residence time for the ophthalmic route.

Spectroscopy With Surface Coils and Decoupling

ClinicalTrials.gov

2015-12-23

Adrenal Cortical Cancer; Brain Cancer; Breast Cancer; CNS Cancer; Colon Cancer; HEENT Cancer; Hodgkin's Disease; Kaposi's Sarcoma; Liver Cancer; Lung Cancer; Non-Hodgkin's Lymphoma; Ovarian Cancer; Pancreatic Cancer; Prostate Cancer; Rectal Cancer; Renal Cancer; Sarcoma; Squamous Cell Carcinoma; Thyroid Cancer

A new nonhuman primate model of severe dry eye.

PubMed

Qin, Yi; Tan, Xiaobo; Zhang, Yingnan; Jie, Ying; Labbe, Antoine; Pan, Zhiqiang

2014-05-01

The aim of this study was to establish a new rhesus monkey model of severe dry eye. A total of 8 rhesus monkeys were used for the study. Four monkeys had their main lacrimal gland and nictitating membrane surgically removed (group 1). Another 4 monkeys had a similar surgery with further application of 50% trichloroacetic acid on the bulbar conjunctiva (group 2). The ocular surface was evaluated before and after the surgery (1, 4, 8, 12, and 24 weeks) using Schirmer-1 test, corneal fluorescein staining, and the lissamine green test. Conjunctival impression cytology was also performed before and 24 weeks after the surgery. Finally, the cornea and the conjunctiva were evaluated using light microscopy. A significant decrease in tear secretion was observed in all operated eyes. Schirmer test data measured were ≤4 mm in all the operated eyes. Slit-lamp examination also revealed abnormal staining in all the operated eyes that remained stable until the end of the experiment. In group 2, corneal fluorescein staining and lissamine green test values were always ≥5 (max 12) and ≥4 (max 9), respectively. Impression cytology specimens of both the treated groups showed conjunctival squamous metaplasia and a decreased number of goblet cells. Under light microscopy, the corneal epithelium appeared irregular with edematous basal epithelial cells. The conjunctiva showed a decreased goblet cell density with infiltration of inflammatory cells. Complete removal of the principal lacrimal gland and nictitating membrane associated with the application of 50% trichloroacetic acid on the conjunctiva could induce severe dry eye in rhesus monkeys.

Quantification of surfactant proteins in tears of patients suffering from dry eye disease compared to healthy subjects.

PubMed

Posa, Andreas; Paulsen, Friedrich; Dietz, Richard; Garreis, Fabian; Sander, Ralph; Schicht, Martin; Sel, Saadettin; Scholz, Michael; Hammer, Christian M; Bräuer, Lars

2018-03-01

To quantify and compare the amounts of surfactant proteins SP-A, SP-B, SP-C and SP-D in the tear fluid collected from patients with dry eye syndrome and from individuals with a healthy ocular surface. Schirmer strips were used to collect tear fluid from both eyes of 241 volunteers (99 men, 142 women; age range: 18-87 years). Dry eye syndrome was diagnosed by ophthalmologists in 125 patients, whereas the healthy control group comprised 116 individuals. The total protein concentration was determined via Bradford assay. The relative concentration of surfactant proteins SP-A through -D was measured by enzyme-linked immuno-sorbent assay (ELISA). The mean relative concentrations of SP-A, SP-C and SP-D were significantly higher in the dry eye group as compared to the healthy controls (p<0.05, one-way ANOVA). SP-B was also detected at a higher concentration in the dry eye group, but the difference to the control group was not statistically significant. The upregulation of SP-A and SP-D in the dry eye group is probably related to these proteins' known antimicrobial and immunomodulatory effects at the ocular surface. It may represent a pathophysiological response to the inflammatory condition of the ocular surface in dry eye. The upregulation of SP-B and SP-C may represent an effort of the lacrimal system to reduce surface tension and thus to counteract the increased tendency of the tear film to tear in dry eye. Copyright © 2017 Elsevier GmbH. All rights reserved.

Polymicrobial and microsporidial keratitis in a patient using Boston scleral contact lens for Sjogren's syndrome and ocular cicatricial pemphigoid.

PubMed

Fernandes, Merle; Sharma, Savitri

2013-04-01

To report a rare case of microsporidial and polymicrobial keratitis in a patient with Sjogren's syndrome and ocular cicatricial pemphigoid. This is a descriptive case report. A 66-year-old lady diagnosed with Sjogren's syndrome (SS) and ocular cicatricial pemphigoid (OCP) presented to us with microbial keratitis after using a Boston sclera contact lens for a painful epithelial defect. After 9 days of medical treatment, she underwent therapeutic penetrating keratoplasty. 10% potassium hydroxide and calcofluor white wet mount revealed microsporidial spores. Gram positive cocci and Gram variable bacilli on Gram stain were identified as Staphylococcus epidermidis and Corynebacterium accolens in culture. Histopathological examination of the corneal tissue confirmed the presence of microsporidial spores. Microsporidal keratitis can occur in patients with severe ocular surface disease due to SS and OCP. Predisposing factors include dry eye, local and systemic immunosuppression and Boston scleral contact lens. Early surgical intervention may be needed to eradicate the infection. Copyright © 2012 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

PLGA-PEG-PLGA hydrogel for ocular drug delivery of dexamethasone acetate.

PubMed

Gao, Yuan; Sun, Yan; Ren, Fuzheng; Gao, Shen

2010-10-01

This study aims to investigate the suitability of thermosensitive triblock polymer poly-(DL-lactic acid-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA as a matrix material for ocular delivery of dexamethasone acetate (DXA). The copolymer was synthesized and evaluated for its thermosensitive and gelation properties. DXA in situ gel-forming solution based on PLGA-PEG-PLGA copolymer of 20% (w/w) was prepared and evaluated for ocular pharmacokinetics in rabbit according to the microdialysis method, which was compared to the normal eye drop. The copolymer with 20% (w/w) had a low critical solution temperature of 32 degrees C, which is close to the surface temperature of the eye. The C(max) of DXA in the anterior chamber for the PLGA-PEG-PLGA solution was 125.2 microg/mL, which is sevenfold higher than that of the eye drop, along with greater area under the concentration-time curves (AUC). These results suggest that the PLGA-PEG-PLGA copolymer is potential thermosensitive in situ gel-forming material for ocular drug delivery, and it may improve the bioavailability, efficacy of some eye drugs.

Ficlatuzumab With or Without Cetuximab in Treating Patients With Cetuximab-Resistant, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-02-02

Head and Neck Basaloid Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage IV Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Nasopharyngeal Keratinizing Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Head and Neck Cancer; Oropharyngeal Cancer; HNSCC

24-Hour Efficacy and Ocular Surface Health with Preservative-Free Tafluprost Alone and in Conjunction with Preservative-Free Dorzolamide/Timolol Fixed Combination in Open-Angle Glaucoma Patients Insufficiently Controlled with Preserved Latanoprost Monotherapy.

PubMed

Konstas, Anastasios-Georgios; Boboridis, Konstadinos G; Kapis, Paraskevas; Marinopoulos, Konstantinos; Voudouragkaki, Irini C; Panayiotou, Dimitrios; Mikropoulos, Dimitrios G; Pagkalidou, Eirini; Haidich, Anna-Bettina; Katsanos, Andreas; Quaranta, Luciano

2017-01-01

The aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD). Prospective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period. Forty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001). In this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy. ClinicalTrials.gov (NCT02802137). Santen.

[The role of microRNAs in head and neck squamous cell carcinoma : Biomarkers for prognosis, therapy selection, and novel therapeutics].

PubMed

Heß, A K; Weichert, W; Budach, V; Tinhofer, I

2016-05-01

Despite recent advances in radiochemotherapy, treatment of locally advanced head and neck squamous cell carcinoma is still challenging, and survival rates have improved only slightly. This is due to the high frequency of metastases and local and/or regional tumor recurrences that have acquired radio- or chemoresistance. MiRNAs regulate diverse processes in tumorigenesis, metastasis, and therapy resistance in head and neck squamous cell carcinoma. Hence, miRNAs are highly valued in biomarker studies. Establishment of the miRNA profiles of oropharyngeal tumors enables personalized treatment selection, since expression of distinct miRNAs can predict the response to two different radiochemotherapy regimens. Development of novel miRNA therapeutics has a high clinical potential for further improving treatment of cancerous disease. The use of nanoparticles with distinct surface modifications as miRNA vectors permits prolonged bioavailability, high efficacy in tumor targeting, and low toxicity. Nevertheless, the efficacy of miRNA therapy has only been shown in animal models to date.

Cetuximab & Nivolumab in Patients With Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-06-13

Squamous Cell Carcinoma of the Oropharynx; Squamous Cell Carcinoma of the Larynx; Squamous Cell Carcinoma of the Oral Cavity; Squamous Cell Carcinoma of the Hypopharynx; Squamous Cell Carcinoma of the Paranasal Sinus; Head and Neck Squamous Cell Carcinoma; Squamous Cell Cancer; Head and Neck Carcinoma

Radiation Therapy With or Without Cisplatin in Treating Patients With Stage III-IV Squamous Cell Carcinoma of the Head and Neck Who Have Undergone Surgery

ClinicalTrials.gov

2017-12-07

Head and Neck Squamous Cell Carcinoma; Laryngeal Squamous Cell Carcinoma, Spindle Cell Variant; Stage III Hypopharyngeal Squamous Cell Carcinoma; Stage III Laryngeal Squamous Cell Carcinoma; Stage III Laryngeal Verrucous Carcinoma; Stage III Oral Cavity Squamous Cell Carcinoma; Stage III Oral Cavity Verrucous Carcinoma; Stage III Oropharyngeal Squamous Cell Carcinoma; Stage IVA Hypopharyngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Squamous Cell Carcinoma; Stage IVA Laryngeal Verrucous Carcinoma; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Oral Cavity Verrucous Carcinoma; Stage IVA Oropharyngeal Squamous Cell Carcinoma

Phase 1b Food Based Modulation of Biomarkers in Human Tissues at High-Risk for Oral Cancer.

ClinicalTrials.gov

2018-03-05

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Salivary Gland Squamous Cell Carcinoma; Stage 0 Hypopharyngeal Cancer; Stage 0 Laryngeal Cancer; Stage 0 Lip and Oral Cavity Cancer; Stage 0 Nasopharyngeal Cancer; Stage 0 Oropharyngeal Cancer; Stage 0 Paranasal Sinus and Nasal Cavity Cancer; Stage I Salivary Gland Cancer; Stage I Squamous Cell Carcinoma of the Hypopharynx; Stage I Squamous Cell Carcinoma of the Larynx; Stage I Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage I Squamous Cell Carcinoma of the Nasopharynx; Stage I Squamous Cell Carcinoma of the Oropharynx; Stage I Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage I Verrucous Carcinoma of the Larynx; Stage I Verrucous Carcinoma of the Oral Cavity; Stage II Salivary Gland Cancer; Stage II Squamous Cell Carcinoma of the Hypopharynx; Stage II Squamous Cell Carcinoma of the Larynx; Stage II Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage II Squamous Cell Carcinoma of the Nasopharynx; Stage II Squamous Cell Carcinoma of the Oropharynx; Stage II Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage II Verrucous Carcinoma of the Larynx; Stage II Verrucous Carcinoma of the Oral Cavity; Stage III Salivary Gland Cancer; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Oral Cavity Squamous Cell Carcinoma; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Nasal Cavity and Paranasal Sinus Cancer; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Oral Cavity Squamous Cell Carcinoma; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Oral Cavity Squamous Cell Carcinoma; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Paranasal Sinus and Nasal Cavity Squamous Cell Carcinoma; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer

Onalespib in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck Receiving Radiation Therapy and Cisplatin

ClinicalTrials.gov

2018-04-23

Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

Erlotinib, Docetaxel, and Radiation Therapy in Treating Patients With Locally Advanced Head and Neck Cancer

ClinicalTrials.gov

2014-06-05

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Verrucous Carcinoma of the Larynx; Stage III Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IVA Squamous Cell Carcinoma of the Larynx; Stage IVA Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVA Squamous Cell Carcinoma of the Oropharynx; Stage IVA Verrucous Carcinoma of the Larynx; Stage IVA Verrucous Carcinoma of the Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Larynx; Stage IVB Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVB Squamous Cell Carcinoma of the Oropharynx; Stage IVB Verrucous Carcinoma of the Larynx; Stage IVB Verrucous Carcinoma of the Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Larynx; Stage IVC Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IVC Squamous Cell Carcinoma of the Oropharynx; Stage IVC Verrucous Carcinoma of the Larynx; Stage IVC Verrucous Carcinoma of the Oral Cavity; Tongue Cancer; Untreated Metastatic Squamous Neck Cancer With Occult Primary

Plasma rich in growth factors membrane as coadjuvant treatment in the surgery of ocular surface disorders.

PubMed

Sanchez-Avila, Ronald M; Merayo-Lloves, Jesús; Riestra, Ana C; Berisa, Silvia; Lisa, Carlos; Sánchez, José Alfonso; Muruzabal, Francisco; Orive, Gorka; Anitua, Eduardo

2018-04-01

To evaluate the safety and efficacy of the surgical use of plasma rich in growth factors fibrin membrane (mPRGF) in different ocular surface pathologies.Fifteen patients with different corneal and conjunctival diseases were included in the study. Patients were grouped according to the use of mPRGF as graft (corneal and/or conjunctival) or dressing; they were also grouped according to the surgical subgroup of intervention (persistent corneal ulcer [PCU], keratoplasty, superficial keratectomy, corneal perforation, and pterygium). Best corrected visual acuity, intraocular pressure (IOP), inflammation control time (ICT), mPRGF AT (PRGF membrane absorption time), and the healing time of the epithelial defect (HTED) were evaluated throughout the clinical follow-up time. Safety assessment was also performed reporting all adverse events.mPRGF showed a total closure of the defect in 13 of 15 patients (86.7%) and a partial closure in 2 patients (13.3%). The mean follow-up time was 11.1 ± 4.2 (4.8-22.8) months, the mean ICT was 2.5 ± 1.1 (1.0-4.0) months, the mean mPRGF AT was 12.4 ± 2.0 (10.0-16.0) days, and for the global HTED the mean was 2.9 ± 1.2 (1-4.8) months. Results showed an improvement in BCVA in all patients, with an overall improvement of 2.9 in Vision Lines. The BCVA significantly improved (P < .05) in the groups of corneal graft and dressing. In the PCU subgroup (6 patients), the healing time of epithelial defect was significantly reduced (P < .05) in patients treated only with the mPRGF in comparison to those which mPRGF therapy was associated to the amniotic membrane. The IOP remained stable (P > .05) throughout the clinical follow-up time. No adverse events were reported after mPRGF use.The mPRGF is effective and safe as coadjuvant treatment in surgeries related with ocular surface disorders, being an alternative to the use of amniotic membrane. The mPRGF accelerates tissue regeneration after ocular surface surgery thus minimizing inflammation and fibrosis.

Amniotic membrane transplantation for ocular disease: a review of the first 233 cases from the UK user group

PubMed Central

Saw, Valerie P J; Minassian, Darwin; Dart, John K G; Ramsay, Andrew; Henderson, Hugo; Poniatowski, Stefan; Warwick, Ruth M; Cabral, Suzanne

2007-01-01

Background Amniotic membrane transplantation (AMT), as a new tool in the armamentarium of therapies available for ocular surface problems, became widely available in the UK in 1998. This study evaluates the indications for treatment, the surgical procedures used, and the results of a subset of the first AMT cases carried out by the group using this nationally available supply. This user group model provides data which is different from that obtained from uncontrolled case series, or clinical trials, and may be more representative of the outcomes that can be expected when a procedure becomes widely available. Methods The first 233 AMTs, performed by the UK user group, were evaluated by audit and outcomes were assessed at 3 months. Results Of the 233 transplants, there were 126 (54.1%) valid outcome returns: the outcome for persistent epithelial defects was a healed and stable surface in 11/35 (31.4%, 95% CI 16.9 to 49.3); for chemical/thermal injuries, a healed uninflamed eye with clear cornea in 5/18 (27.8%, 95% CI 9.7 to 53.4); for bullous keratopathy a pain‐free, stable surface without bullae in 4/18 (22.2%, 95% CI 6.4 to 47.6); for ocular surface reconstruction, an epithelialised uninflamed conjunctiva without scarring in 12/23 (52.2%, 95% CI 30.6 to 73.2); and for limbal stem cell deficiency, a corneal phenotype in 4/7 (57.1%). The operative technique least associated with failure was use of a bandage contact lens at the end of the procedure (OR 0.19, 95% CI 0.06 to 0.59, p = 0.004). Previous treatment with topical steroids was significantly associated with failure (OR 5.70, 95% CI 1.77 to 18.43, p = 0.004). Conclusion Although the outcome criteria used in this study were stringent, and the follow‐up duration was short, the results of AMT by this user group were generally less favourable than those of previously reported case series. Controlled clinical trials would improve the quality of evidence for use of amniotic membrane in ocular disease. PMID:17314154

Plasma rich in growth factors eye drops to treat secondary ocular surface disorders in patients with glaucoma

PubMed Central

Sánchez-Avila, Ronald M; Merayo-Lloves, Jesus; Fernández, Maria Laura; Rodríguez-Gutiérrez, Luis Alberto; Rodríguez-Calvo, Pedro Pablo; Fernández-Vega Cueto, Andres; Muruzabal, Francisco; Orive, Gorka; Anitua, Eduardo

2018-01-01

Purpose To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) eye drops in patients with glaucoma with secondary ocular surface disorders (OSDs) due to surgeries and topical hypotensive drugs use. Materials and methods A retrospective case-series study design was used including six patients (eight eyes) diagnosed with glaucoma who received surgical (nonpenetrating deep sclerectomy and/or trabeculectomy) and medical treatments (hypotensive eye drops) to control intraocular pressure (IOP) and who developed secondary OSDs, unresponsive to conventional treatments. Patients were treated with PRGF eye drops (four times a day). Outcome measures were ocular surface disease index (OSDI), best-corrected visual acuity (BCVA, in logarithm of the minimum angle of resolution), visual analog scale (VAS), frequency and severity of symptoms, and IOP. The safety of the treatment was also evaluated. Results Six patients (seven eyes with open-angle glaucoma and one eye with uveitic glaucoma) treated with PRGF eye drops were evaluated. Mean age was 71 years (SD=7.2, range 58–79 years). Five were female and one was male. The mean treatment time was 21.8 weeks (SD=9.0, range 12–36 weeks). The mean time to reach closure of the corneal ulcer was 14.5 (SD=5.5) weeks. A statistical significant reduction in OSDI scale (50.6%), VAS frequency (53.1%), VAS severity (42.0%), and a 41.8% improvement in BCVA were observed (p<0.05). IOP also decreased by 16.6% (p=0.010). Only one of the six patients reported itching in both eyes as an adverse event (AE); however, the patient continued with the PRGF eye drops until the end of therapy; the remaining patients did not report any AEs during the follow-up period. Conclusions In patients with glaucoma and secondary OSDs refractive to conventional treatments, the treatment with PRGF eye drops could be considered a possible therapeutic option, because it demonstrates an improvement in the signs and symptoms of the ocular surface, as well as a better control of the IOP. This is an initial research work that can open doors for future research to confirm these findings. PMID:29760570

Plasma rich in growth factors eye drops to treat secondary ocular surface disorders in patients with glaucoma.

PubMed

Sánchez-Avila, Ronald M; Merayo-Lloves, Jesus; Fernández, Maria Laura; Rodríguez-Gutiérrez, Luis Alberto; Rodríguez-Calvo, Pedro Pablo; Fernández-Vega Cueto, Andres; Muruzabal, Francisco; Orive, Gorka; Anitua, Eduardo

2018-01-01

To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) eye drops in patients with glaucoma with secondary ocular surface disorders (OSDs) due to surgeries and topical hypotensive drugs use. A retrospective case-series study design was used including six patients (eight eyes) diagnosed with glaucoma who received surgical (nonpenetrating deep sclerectomy and/or trabeculectomy) and medical treatments (hypotensive eye drops) to control intraocular pressure (IOP) and who developed secondary OSDs, unresponsive to conventional treatments. Patients were treated with PRGF eye drops (four times a day). Outcome measures were ocular surface disease index (OSDI), best-corrected visual acuity (BCVA, in logarithm of the minimum angle of resolution), visual analog scale (VAS), frequency and severity of symptoms, and IOP. The safety of the treatment was also evaluated. Six patients (seven eyes with open-angle glaucoma and one eye with uveitic glaucoma) treated with PRGF eye drops were evaluated. Mean age was 71 years (SD=7.2, range 58-79 years). Five were female and one was male. The mean treatment time was 21.8 weeks (SD=9.0, range 12-36 weeks). The mean time to reach closure of the corneal ulcer was 14.5 (SD=5.5) weeks. A statistical significant reduction in OSDI scale (50.6%), VAS frequency (53.1%), VAS severity (42.0%), and a 41.8% improvement in BCVA were observed ( p <0.05). IOP also decreased by 16.6% ( p =0.010). Only one of the six patients reported itching in both eyes as an adverse event (AE); however, the patient continued with the PRGF eye drops until the end of therapy; the remaining patients did not report any AEs during the follow-up period. In patients with glaucoma and secondary OSDs refractive to conventional treatments, the treatment with PRGF eye drops could be considered a possible therapeutic option, because it demonstrates an improvement in the signs and symptoms of the ocular surface, as well as a better control of the IOP. This is an initial research work that can open doors for future research to confirm these findings.

Immunocytochemistry of cell surface heparan sulfate proteoglycan in mouse tissues. A light and electron microscopic study.

PubMed

Hayashi, K; Hayashi, M; Jalkanen, M; Firestone, J H; Trelstad, R L; Bernfield, M

1987-10-01

The core protein of the proteoglycan at the cell surface of NMuMG mouse mammary epithelial cells bears both heparan and chondroitin sulfate chains and is recognized by the monoclonal antibody 281-2. Using this antibody and the peroxidase-antiperoxidase staining technique in adult mouse tissues, we found that the antibody recognizes the antigen in a highly restricted distribution, staining a variety of epithelial cells but no cells derived from embryonic mesoderm or neural crest. The antibody fails to stain any stromal (mesenchymal) or neuronal cells, with the exception of plasma cells and Leydig cells. Squamous and transitional epithelia stain intensely over their entire surfaces, whereas cuboidal and columnar epithelia stain moderately and only at the lateral surface of the basal cells. Within squamous and transitional epithelial tissues that undergo physiological regeneration (e.g., epidermis), the most superficial and differentiated cell types fail to stain. Within glandular and branched epithelia (e.g., pancreas), the secretory alveolar cells fail to stain. When evaluated by electron microscopy, granular deposits of stain are seen on the plasma membrane, especially on lateral surfaces, but none are noted within the cells or the basement membrane. These results indicate that in adult tissues the core protein of this heparan sulfate-rich proteoglycan is expressed almost exclusively at epithelial cell surfaces. Expression appears to be lost as the cells become either mature or highly differentiated.

Characterization of human ocular mucin secretion mediated by 15(S)-HETE.

PubMed

Jumblatt, James E; Cunningham, Lauren T; Li, Yang; Jumblatt, Marcia M

2002-11-01

The eicosanoid 15-(S)-hydroxy-5,8,11,13-eicosatetraenoic acid [15(S)-HETE] is reported to stimulate mucin production in both airway and ocular surface epithelia. The current study was undertaken to evaluate the effects of 15(S)-HETE on secretion of specific ocular mucins by human conjunctiva. Segments of human bulbar conjunctival tissue were incubated with 15(S)-HETE (1-1000 nM) for 30 minutes at 37 degrees C. Secretion of human ocular mucins MUC1, MUC2, MUC4, and MUC5AC into the incubation media was measured by dot-blot immunoassay using antibodies directed to unique mucin polypeptide epitopes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting were used to verify the specificity of anti-mucin antibody binding and to investigate the presence of MUC1 mucin in human tears. 15(S)-HETE (10(-8)-10(-6) M) stimulated secretion of conjunctival mucins in a concentration-dependent manner. Significant increases in total mucin secretion were observed at 10(-7) M 15(S)-HETE with a maximum response (>50% increase above controls) at 10(-6) M. Results of immunoassays showed that 15(S)-HETE differentially stimulates secretion of MUC1 mucin with no detectable effects on MUC2, MUC4, or MUC5AC release. Western analysis of tear samples from human volunteers indicated that MUC1 is a component of the preocular tear film. The results demonstrate that 15(S)-HETE is a selective secretogogue for MUC1 in isolated human conjunctival tissue. Although the biochemical mechanism(s) and cellular origins of MUC1 secretion remain to be established, the ubiquitous expression of MUC1 in corneal and conjunctival epithelia and its presence in human tears suggest that secreted MUC1 may contribute to the mucin layer that coats and protects the ocular surface.

Radiation Therapy With Durvalumab or Cetuximab in Treating Patients With Stage III-IVB Head and Neck Cancer Who Cannot Take Cisplatin

ClinicalTrials.gov

2018-06-15

Head and Neck Squamous Cell Carcinoma; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

Cisplatin, Intensity-Modulated Radiation Therapy, and Pembrolizumab in Treating Patients With Stage III-IV Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-05-18

CDKN2A-p16 Negative; Stage III Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage III Laryngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7

Using typical endoscopic features to diagnose esophageal squamous papilloma.

PubMed

Wong, Ming-Wun; Bair, Ming-Joug; Shih, Shou-Chuan; Chu, Cheng-Hsin; Wang, Horng-Yuan; Wang, Tsang-En; Chang, Chen-Wang; Chen, Ming-Jen

2016-02-21

To better understand some of the superficial tiny lesions that are recognized as squamous papilloma of the esophagus (SPE) and receive a different pathological diagnosis. All consecutive patients with esophageal polypoid lesions detected by routine endoscopy at our Endoscopy Centre between October 2009 and June 2014 were retrospectively analysed. We enrolled patients with SPE or other superficial lesions to investigate four key endoscopic appearances (whitish color, exophytic growth, wart-like shape, and surface vessels) and used narrow band imaging (NBI) to distinguish their differences. These series endoscopic images of each patient were retrospectively reviewed by three experienced endoscopists with no prior access to the images. All lesion specimens obtained by forceps biopsy were fixed in formalin and processed for pathological examination. The following data were collected from patient medical records: gender, age, indications for esophagogastroduodenoscopy, and endoscopic characteristics including lesion location, number, color, size, surface morphology, surrounding mucosa, and surface vessels under NBI. Clinicopathological features were also compared. During the study period, 41 esophageal polypoid lesions from 5698 endoscopic examinations were identified retrospectively. These included 24 patients with pathologically confirmed SPE, 11 patients with squamous hyperplasia, three patients with glycogenic acanthosis, two patients with ectopic sebaceous glands, and one patient with a xanthoma. In the χ (2) test, exophytic growth (P = 0.003), a wart-like shape (P < 0.001), and crossing surface vessels under NBI (P = 0.001) were more frequently observed in SPE than in other lesion types. By contrast, there was no significant difference regarding the appearance of a whitish color between SPE and other lesion types (P = 0.872). The most sensitive characteristic was wart-like projections (81.3%) and the most specific was exophytic growth (87.5%). Promising positive predictive values of 84.2%, 80.8%, and 82.6% were noted for exophytic growth, wart-like projections, and surface vessel crossing on NBI, respectively. The use of three key typical endoscopic appearances--exophytic growth, a wart-like shape, and vessel crossing on the lesion surface under NBI--has a promising positive predictive value of 88.2%. This diagnostic triad is useful for the endoscopic diagnosis of SPE.

Using typical endoscopic features to diagnose esophageal squamous papilloma

PubMed Central

Wong, Ming-Wun; Bair, Ming-Joug; Shih, Shou-Chuan; Chu, Cheng-Hsin; Wang, Horng-Yuan; Wang, Tsang-En; Chang, Chen-Wang; Chen, Ming-Jen

2016-01-01

AIM: To better understand some of the superficial tiny lesions that are recognized as squamous papilloma of the esophagus (SPE) and receive a different pathological diagnosis. METHODS: All consecutive patients with esophageal polypoid lesions detected by routine endoscopy at our Endoscopy Centre between October 2009 and June 2014 were retrospectively analysed. We enrolled patients with SPE or other superficial lesions to investigate four key endoscopic appearances (whitish color, exophytic growth, wart-like shape, and surface vessels) and used narrow band imaging (NBI) to distinguish their differences. These series endoscopic images of each patient were retrospectively reviewed by three experienced endoscopists with no prior access to the images. All lesion specimens obtained by forceps biopsy were fixed in formalin and processed for pathological examination. The following data were collected from patient medical records: gender, age, indications for esophagogastroduodenoscopy, and endoscopic characteristics including lesion location, number, color, size, surface morphology, surrounding mucosa, and surface vessels under NBI. Clinicopathological features were also compared. RESULTS: During the study period, 41 esophageal polypoid lesions from 5698 endoscopic examinations were identified retrospectively. These included 24 patients with pathologically confirmed SPE, 11 patients with squamous hyperplasia, three patients with glycogenic acanthosis, two patients with ectopic sebaceous glands, and one patient with a xanthoma. In the χ2 test, exophytic growth (P = 0.003), a wart-like shape (P < 0.001), and crossing surface vessels under NBI (P = 0.001) were more frequently observed in SPE than in other lesion types. By contrast, there was no significant difference regarding the appearance of a whitish color between SPE and other lesion types (P = 0.872). The most sensitive characteristic was wart-like projections (81.3%) and the most specific was exophytic growth (87.5%). Promising positive predictive values of 84.2%, 80.8%, and 82.6% were noted for exophytic growth, wart-like projections, and surface vessel crossing on NBI, respectively. CONCLUSION: The use of three key typical endoscopic appearances - exophytic growth, a wart-like shape, and vessel crossing on the lesion surface under NBI - has a promising positive predictive value of 88.2%. This diagnostic triad is useful for the endoscopic diagnosis of SPE. PMID:26900297

Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-06-19

Recurrent Hypopharyngeal Squamous Cell Carcinoma; Recurrent Laryngeal Squamous Cell Carcinoma; Recurrent Laryngeal Verrucous Carcinoma; Recurrent Lip and Oral Cavity Squamous Cell Carcinoma; Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary; Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma; Recurrent Oral Cavity Verrucous Carcinoma; Recurrent Oropharyngeal Squamous Cell Carcinoma; Recurrent Salivary Gland Carcinoma; Salivary Gland Squamous Cell Carcinoma; Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary; Stage IV Hypopharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Major Salivary Gland Cancer AJCC v7; Stage IVA Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Laryngeal Verrucous Carcinoma AJCC v7; Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Major Salivary Gland Cancer AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Cancer AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Laryngeal Verrucous Carcinoma AJCC v7; Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Major Salivary Gland Cancer AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Cancer AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Laryngeal Verrucous Carcinoma AJCC v7; Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Major Salivary Gland Cancer AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Cancer AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7; Tongue Carcinoma; Untreated Metastatic Squamous Cell Carcinoma to Neck With Occult Primary

A novel technique of contrast-enhanced optical coherence tomography imaging in evaluation of clearance of lipids in human tears.

PubMed

Napoli, Pietro Emanuele; Coronella, Franco; Satta, Giovanni Maria; Fossarello, Maurizio

2014-01-01

The aim of this work was to gather preliminary data in different conditions of healthy eyes, aqueous tear deficient dry eyes, obstructive meibomian gland disease (MGD) and non-obvious obstructive MGD (NOMGD) individuals, using a new, contrast-enhanced optical coherence tomography (OCT) imaging method to evaluate the clearance of lipids in human tears. Eighty-two adult patients presenting with complaints of ocular irritation were studied for abnormalities of the ocular surface and classified as healthy (n = 21), aqueous tear deficient dry eyes (n = 20), obstructive MGD (n = 15) and NOMGD (n = 26) individuals. A lipid-based tracer, containing an oil-in-water emulsion, was used to obtain an enhanced OCT imaging of the lower tear meniscus. After instillation, a dramatic initial increase of reflectivity of the lower tear meniscus was detected by OCT, followed by a decay back to baseline values over time. Based on this finding, the clearance of lipids was measured in real-time by Fourier-domain anterior segment OCT. The differences in the clearance of lipids among the four groups as well as the correlations between symptom questionnaire score, standardized visual scale test, fluorescein break-up time, ocular surface fluorescein staining score, Schirmer I test scores were found to be statistically significant. The individual areas under the curve of the clearance of lipids calculated by the receiver operating characteristic curve technique ranged from 0.66 to 0.98, suggesting reliable sensitivity and specificity of lipid-enhanced OCT imaging. This new technique of contrast-enhanced OCT imaging of the tear film following lipid-based tracer instillation provides a measure of the clearance of lipids. The quantitative values found are in agreement with other methods of evaluation of the lacrimal system. An improvement of the clinician's ability in the diagnosis and understanding of abnormalities of the ocular surface may be achieved by this simple approach.

Effects of topical acne treatment on the ocular surface in patients with acne vulgaris.

PubMed

Aslan Bayhan, Seray; Bayhan, Hasan Ali; Çölgeçen, Emine; Gürdal, Canan

2016-12-01

To assess the ocular side effects during topical retinoid-antibiotic combination treatment in patients with facial acne vulgaris. Forty-three patients applying topical isotretinoin+erythromycin combination (isotrexin gel, GlaxoSmithKline) once daily for the treatment of acne vulgaris were enrolled. Full ophthalmologic examination, Schirmer test (with topical anesthesia), fluorescein break-up time (BUT), corneal fluorescein staining and tear osmolarity measurement with the TearLab system (TearLab Corporation) were carried out before and at the end of the first month of the treatment. For evaluation of symptoms participants completed the ocular surface disease index (OSDI) questionnaire at each visit. The mean age of the patients was 23.16±3.03 (18-30) years. Mean tear osmolarity increased significantly from 282.09±8.95 mOsm/L at baseline to 300.39±16.65 mOsm/L after the treatment (p<0.001). BUT decreased from an average of 11.93±1.12s at baseline to 6.65±3.03s at the end of the first month (p<0.001). The OSDI score worsened significantly (5.41±3.65 vs 21.53±12.95, p<0.001) and punctate epitheliopathy was seen in 51% of eyes after the treatment. The average Schirmer values were 13.09±1.90 and 12.41±2.44mm/5min before and at the end of the first month of the treatment, respectively (p=0.117). The findings of this study indicate that topical retinoid-antibiotic combination treatment causes significant signs and symptoms of dry eye. Patients receiving topical treatment for acne should be evaluated regularly to ensure the timely detection and treatment of pathologic signs on the ocular surface. Copyright © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Predicting success with silicone-hydrogel contact lenses in new wearers.

PubMed

Best, Nigel; Drury, Laura; Wolffsohn, James S

2013-10-01

to evaluate changes in tear metrics and ocular signs induced by six months of silicone-hydrogel contact lens wear and the difference in baseline characteristics between those who successfully continued in contact lens wear compared to those that did not. Non-invasive Keratograph, Tearscope and fluorescein tear break-up times (TBUTs), tear meniscus height, bulbar and limbal hyperaemia, lid-parallel conjunctival folds (LIPCOF), phenol red thread, fluorescein and lissamine-green staining, and lid wiper epitheliopathy were measured on 60 new contact lens wearers fitted with monthly silicone-hydrogels (average age 36±14 years, 40 females). Symptoms were evaluated by the Ocular Surface Disease Index (OSDI). After six months full time contact lens wear the above metrics were re-measured on those patients still in contact lens wear (n=33). The initial measurements were also compared between the group still wearing lenses after six months and those who had ceased lens wear (n=27). There were significant changes in tear meniscus height (p=0.031), bulbar hyperaemia (p=0.011), fluorescein TBUT (p=0.027), corneal (p=0.007) and conjunctival (p=0.009) staining, LIPCOF (p=0.011) and lid wiper epitheliopathy (p=0.002) after six months of silicone-hydrogel wear. Successful wearers had a higher non-invasive (17.0±8.2s vs 12.0±5.6s; p=0.001) and fluorescein (10.7±6.4s vs 7.5±4.7s; p=0.001) TBUT than drop-outs, although OSDI (cut-off 4.2) was also a strong predictor of success. Silicone-hydrogel lenses induced significant changes in the tear film and ocular surface as well as lid margin staining. Wettability of the ocular surface is the main factor affecting contact lens drop-out. Copyright © 2013 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Topical Ocular Drug Delivery to the Back of the Eye by Mucus-Penetrating Particles

PubMed Central

Schopf, Lisa R.; Popov, Alexey M.; Enlow, Elizabeth M.; Bourassa, James L.; Ong, Winston Z.; Nowak, Pawel; Chen, Hongming

2015-01-01

Purpose: Enhanced drug exposure to the ocular surface typically relies on inclusion of viscosity-enabling agents, whereas delivery to the back of the eye generally focuses on invasive means, such as intraocular injections. Using our novel mucus-penetrating particle (MPP) technology, which rapidly and uniformly coats and penetrates mucosal barriers, we evaluated if such drug formulations could increase ocular drug exposure and improve topical drug delivery. Methods: Pharmacokinetic (PK) profiling of topically administered loterprednol etabonate formulated as MPP (LE-MPP) was performed in rabbits and a larger species, the mini-pig. Pharmacodynamic evaluation was done in a rabbit model of VEGF-induced retinal vascular leakage. Cellular potency and PK profile were determined for a second compound, KAL821, a novel receptor tyrosine kinase inhibitor (RTKi). Results: We demonstrated in animals that administration of LE-MPP increased exposure at the ocular surface and posterior compartments. Furthermore using a rabbit vascular leakage model, we demonstrated that biologically effective drug concentrations of LE were delivered to the back of the eye using the MPP technology. We also demonstrated that a novel RTKi formulated as MPPs provided drug levels to the back of the eye above its cellular inhibitory concentration. Conclusions: Topical dosing of MPPs of LE or KAL821 enhanced drug exposure at the front of the eye, and delivered therapeutically relevant drug concentrations to the back of the eye, in animals. Translational Relevance: These preclinical data support using MPP technology to engineer topical formulations to deliver therapeutic drug levels to the back of the eye and could provide major advancements in managing sight-threatening diseases. PMID:26101724

Tear Film Osmolarity in Subjects with Acute Allergic Rhinoconjunctivitis.

PubMed

Nitoda, Eirini; Lavaris, Anastasios; Laios, Konstantinos; Androudi, Sophia; Kalogeropoulos, Chris D; Tsatsos, Michael; Damaskos, Christos; Garmpis, Nikolaos; Moschos, Marilita M

2018-01-01

Acute allergic rhinoconjuctivitis is the most common form of ocular allergies. The pathogenetic mechanisms are based on an immunoglobulin E (IgE)-mediated hypersensitivity reaction. On the other hand, tear osmolarity has been suggested to be an index of ocular surface damage and inflammation. These data were the motive to investigate the levels of tear osmolarity in subjects with acute allergic rhinoconjuctivitis, before and after administration of artificial tears. Forty-five subjects with acute allergic rhinoconjuctivitis were randomly divided into three groups, based on the type of artificial tears that they received: Group A (Thera tears), Group B (Wet therapy) and Group C (Tears Naturale free). The eye drops were administered six times a day for 60 days and all subjects underwent grading of subjective symptoms and clinical examination at baseline and at the end of the treatment. The diagnosis of severe eye disease, which was based on ocular surface disease index (OSDI; Allergan, Inc, Irvine, CA, USA) and tear osmolarity values, concerned all patients at baseline. Although the administration of artificial tears significantly ameliorated the symptoms and the ocular variables in all groups, the results were better in the first group. Tear osmolarity was strongly and negatively correlated with tear film breakup time (BUT) and Schirmer I test at 2 months. Contrariwise, symptoms were eliminated, when tear osmolarity was decreased. Acute allergic rhinoconjuctivitis is characterized by tear hyperosmolarity, which can be rehabilitated with the administration of hypotonic artificial tears. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

SB-715992 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

ClinicalTrials.gov

2017-01-13

Metastatic Squamous Neck Cancer With Occult Primary Squamous Cell Carcinoma; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity

Contact lens strategies for the patient with dry eye.

PubMed

Sindt, Christine W; Longmuir, Reid A

2007-10-01

Dry eye is the most common reason for contact lens (CL) discontinuation, and the patient with pre-existing dry eye presents particular challenges to the CL fitter. Poor tear film quality/stability, oxygen deprivation, lens deposits, and adverse reactions to CL solutions all contribute to dry eye, and lid disease, allergies, environmental factors, and medications can further hamper successful CL wear by the patient with dry eye. Health and comfort of the ocular surface is affected by the water content, ionicity, oxygen permeability, and modulus of elasticity of the lens, as well as by surface characteristics, such as protein, lipid, and mucin deposition; protein adsorption; and wettability. The choice of CL cleaning solutions with regard to action, cytotoxicity, and biocompatibility are as important as the choice of the CL itself. With appropriate management of the lid, meibomian gland, and ocular surface conditions that produce dry eye, careful selection of lenses and solutions, and vigilant follow-up, successful CL wear should be achievable for the dry eye patient.

ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment

ClinicalTrials.gov

2018-03-02

Oral Cavity Neoplasm; Oropharyngeal Neoplasm; Stage I Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage I Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage II Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage II Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

Selenomethionine in Reducing Mucositis in Patients With Locally Advanced Head and Neck Cancer Who Are Receiving Cisplatin and Radiation Therapy

ClinicalTrials.gov

2014-08-08

Chemotherapeutic Agent Toxicity; Mucositis; Radiation Toxicity; Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage III Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Xerostomia

VX-970, Cisplatin, and Radiation Therapy in Treating Patients With Locally Advanced HPV-Negative Head and Neck Squamous Cell Carcinoma

ClinicalTrials.gov

2018-06-11

Head and Neck Squamous Cell Carcinoma; Human Papillomavirus Negative; Stage III Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v6 and v7; Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IV Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7; Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma AJCC v7; Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v7

Malassezia spp on the periocular skin of dogs and their association with blepharitis, ocular discharge, and the application of ophthalmic medications.

PubMed

Newbold, Georgina M; Outerbridge, Catherine A; Kass, Philip H; Maggs, David J

2014-06-01

To determine how frequently Malassezia spp were identified on the periocular skin of dogs and assess the respective associations between the presence of Malassezia spp on the periocular skin and blepharitis, ocular discharge, and the application of ophthalmic medications. Prospective clinical study. 167 eyelids of 84 dogs. Samples obtained from the surface of the eyelid skin by use of adhesive tape were evaluated cytologically for the presence of Malassezia spp. Dogs were grouped on the basis of the presence of blepharitis, nature of ocular discharge, and whether ophthalmic medications were applied, and the proportion of samples with Malassezia spp was compared among the groups. Malassezia spp were detected in 19 samples, of which 15 were obtained from eyes without blepharitis and 14 were obtained from eyes treated with topical ophthalmic medications. The proportion of samples with Malassezia spp was significantly higher for eyes with ocular discharge than for eyes without ocular discharge, especially if that discharge was mucoid or mucopurulent, and for eyes that were treated with aqueous-based medications only or a combination of oil- and aqueous-based medications than for eyes that were not treated. Malassezia organisms were detected on the periocular skin of 3 of 56 (5%) clinically normal dogs. Malassezia organisms were also frequently found on the periocular skin of dogs that had mucoid or mucopurulent ocular discharge or that were administered topical aqueous-based ophthalmic medications, and the periocular skin of these dogs should be cytologically evaluated for Malassezia organisms.

Bandage soft contact lenses for ocular graft-versus-host disease

PubMed Central

Inamoto, Yoshihiro; Sun, Yi-Chen; Flowers, Mary E. D.; Carpenter, Paul A.; Martin, Paul J.; Li, Peng; Wang, Ruikang; Chai, Xiaoyu; Storer, Barry E.; Shen, Tueng T.; Lee, Stephanie J.

2015-01-01

To examine safety and efficacy of bandage soft contact lenses (BSCLs) for ocular chronic graft-versus host disease (GVHD), we conducted a phase II clinical trial. Extended-wear BSCLs were applied under daily topical antibiotics prophylaxis. Patients completed standardized symptom questionnaires at enrollment and at 2 weeks, 4 weeks and 3 months afterwards. Ophthalmologic assessment was performed at enrollment, at 2 weeks and afterwards as medically needed. Assessments at follow-up were compared with baseline by paired t-test. Nineteen patients with ocular GVHD who remained symptomatic despite conventional treatments were studied. The mean Lee eye subscale score was 75.4 at enrollment, and improved significantly to 63.2 at 2 weeks (p=0.01), to 61.8 at 4 weeks (p=0.005) and to 56.3 at 3 months (p=0.02). The ocular surface disease index score and 11-point eye symptom ratings also improved significantly. According to the Lee eye subscale, clinically meaningful improvement was observed in 9 patients (47%) at 2 weeks, in 11 (58%) at 4 weeks and in 9 (47%) at 3 months. Visual acuity improved significantly at 2 weeks compared with enrollment values. Based on slit lamp exam at 2 weeks, punctate epithelial erosions improved in 58% of the patients, showed stability in 16% and worsened in 5%. No corneal ulceration or ocular infection occurred. BSCLs are a widely available, safe and effective treatment option that improves manifestations of ocular graft-versus host disease in approximately 50% of patients. This study was registered at www.clinicaltrials.gov as NCT01616056. PMID:26189353

Clinical and histologic description of ocular anatomy in captive black-tailed prairie dogs (Cynomys ludovicianus).

PubMed

Meekins, Jessica M; Eshar, David; Rankin, Amy J; Henningson, Jamie N

2016-03-01

To describe the clinical and histologic ocular anatomy of the black-tailed prairie dog (PD). Seventeen captive black-tailed PDs (11 males and six females), ranging in age from approximately 4 months to 4.5 years. Complete ocular examinations, including slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, were performed under isoflurane anesthesia. The globes (n = 2) of one black-tailed PD were harvested immediately after euthanasia and processed after formalin fixation. Staining with hematoxylin-eosin, cytokeratin AE1/AE3, glial fibrillary acidic protein, chromogranin A, claudin-5, smooth muscle actin, and vimentin was performed for light microscopic evaluation. A thick mucinous precorneal tear film was present on the ocular surface. A vestigial nictitating membrane was identified in the medial canthus area. The limbus was heavily pigmented, the iris was a dark homogenous brown, and the pupil was round. Funduscopically, there was no tapetum lucidum, the retinal vascular pattern was holangiotic, and a horizontally elongated optic disk was visualized. The most common ocular abnormalities were acquired eyelid margin defects, present in seven eyes of six black-tailed PDs (35.3%). On histologic examination, the retina was asymmetric, thicker below the optic disk and thinner above it. The black-tailed PD fundus is atapetal with a holangiotic retinal vessel pattern and a horizontally elongated optic disk. Acquired lesions of the peri-ocular and eyelid region were the most common documented abnormality. Unique anatomic features of the globe and adnexa were confirmed with histologic and immunohistochemical analysis. © 2015 American College of Veterinary Ophthalmologists.

Thiolated nanostructured lipid carriers as a potential ocular drug delivery system for cyclosporine A: Improving in vivo ocular distribution.

PubMed

Shen, Jie; Deng, Yanping; Jin, Xuefeng; Ping, Qineng; Su, Zhigui; Li, Lejun

2010-12-15

Ophthalmic drug delivery with long pre-corneal retention time and high penetration into aqueous humor and intraocular tissues is the key-limiting factor for the treatment of ocular diseases and disorders. Within this study, the conjugate of cysteine-polyethylene glycol monostearate (Cys-PEG-SA) was synthesized and was used to compose the thiolated nanostructured lipid carrier (Cys-NLC) as a potential nanocarrier for the topical ocular administration of cyclosporine A (CyA). The rapid cross-linking process of Cys-PEG-SA in vitro was found in simulated physiological environment. The in vitro CyA release from Cys-NLC was slower than that of non-thiolated nanostructured lipid carriers (NLC) due to the cross-linking of thiomers on the surface of nanocarriers. After topical ocular administration in rabbits, the in vivo ocular distribution of CyA was investigated in comparison of Cys-NLC with non-thiolated NLCs and oil solution. The results showed that CyA concentration in systemic blood was very low and close to the detection limit. The area-under-the-curve (AUC(0-24h)) and mean retention time (MRT(0-24h)) of Cys-NLC group in aqueous humor, tear and eye tissues were significantly higher than that of oil solution, non-thiolated NLCs (p<0.05). These results demonstrated that the thiolated NLC could deliver high level of CyA into intraocular tissues due to its bioadhesive property and sustained release characteristics. Copyright © 2010 Elsevier B.V. All rights reserved.

Burning Eye Syndrome: Do Neuropathic Pain Mechanisms Underlie Chronic Dry Eye?

PubMed

Kalangara, Jerry P; Galor, Anat; Levitt, Roy C; Felix, Elizabeth R; Alegret, Ramon; Sarantopoulos, Constantine D

2016-04-01

Dry eye is a multi-factorial disorder that manifests with painful ocular symptoms and visual disturbances, which can only be partly attributed to tear dysfunction. This disorder may also involve neuroplasticity in response to neuronal injury. This review will emphasize the key characteristics of dry eye pain and its pathologic mechanisms, making the argument that a subset of dry eye represents a neuropathic pain disorder of the eye, more appropriately called "burning eye syndrome." A literature review was conducted using a PubMed search focusing on dry eye, corneal nociception, and neuropathic pain. Articles were reviewed and those discussing clinical course, pathophysiology, and neuronal regulation of chronic ocular pain as related to dry eye were summarized. We found that there is a discordance between ocular pain and dryness on the ocular surface. Although tear dysfunction may be one of the initial insults, its persistence may be associated with repeated ocular sensory nerve injury leading to an acute-to-chronic pain transition associated with neuropathologic changes (peripheral and central sensitization), neuronal dysfunction, and spontaneous ocular pain. Dry eye is becoming a major health concern due to its increasing incidence, significant morbidity, and economic burden. Recent evidence suggests that a subset of dry eye may be better represented as a chronic neuropathic pain disorder due to its features of dysesthesia, spontaneous pain, allodynia, and hyperalgesia. Future therapies targeted at the underlying neuroplasticity may yield improved efficacy for patients with this subset of dry eye, which we term "burning eye syndrome." © 2015 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cisplatin and Radiation Therapy With or Without Erlotinib Hydrochloride in Treating Patients With Stage III or Stage IV Head and Neck Cancer

ClinicalTrials.gov

2013-05-08

Stage III Squamous Cell Carcinoma of the Hypopharynx; Stage III Squamous Cell Carcinoma of the Larynx; Stage III Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage III Squamous Cell Carcinoma of the Nasopharynx; Stage III Squamous Cell Carcinoma of the Oropharynx; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx

Functional lacrimal gland regeneration by transplantation of a bioengineered organ germ

PubMed Central

Hirayama, Masatoshi; Ogawa, Miho; Oshima, Masamitsu; Sekine, Yurie; Ishida, Kentaro; Yamashita, Kentaro; Ikeda, Kazutaka; Shimmura, Shigeto; Kawakita, Tetsuya; Tsubota, Kazuo; Tsuji, Takashi

2013-01-01

The lacrimal gland has a multifaceted role in maintaining a homeostatic microenvironment for a healthy ocular surface via tear secretion. Dry-eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye diseases that cause corneal epithelial damage and results in significant loss of vision and a reduction in the quality of life. Here we demonstrate orthotopic transplantation of bioengineered lacrimal gland germs into adult mice with an extra-orbital lacrimal gland defect, a mouse model that mimics the corneal epithelial damage caused by lacrimal gland dysfunction. The bioengineered lacrimal gland germs and harderian gland germs both develop in vivo and achieve sufficient physiological functionality, including tear production in response to nervous stimulation and ocular surface protection. This study demonstrates the potential for bioengineered organ replacement to functionally restore the lacrimal gland. PMID:24084941

Influence of investment, disinfection, and storage on the microhardness of ocular resins.

PubMed

Goiato, Marcelo Coelho; dos Santos, Daniela Micheline; Gennari-Filho, Humberto; Zavanelli, Adriana Cristina; Dekon, Stefan Fiuza de Carvalho; Mancuso, Daniela Nardi

2009-01-01

The longevity of an ocular prosthesis is directly related to the resistance to erosion of its material. The purpose of this study was to evaluate the effects of chemical disinfection and the method of investment on the microhardness of ocular prosthesis acrylic resin. Thirty-two test specimen investments were obtained in two silicones. A segment was cut in each test specimen, and each specimen was fixed in an acrylic disk. The specimens were then polished and submitted to the first microhardness test before immersion in distilled water and incubation for 2 months. During this 2-month period, the specimens were immersed in a water bath at 37 degrees C and were disinfected daily; half were disinfected with neutral soap and the other half were disinfected with 4% chlorhexidine gluconate. After the storage phase and disinfection, a second microhardness test was performed. The surface microhardness values for the acrylic resins were submitted to ANOVA, followed by the Tukey test. The disinfection and the period of storage did not statistically influence the surface microhardness of the acrylic resin, independent of the method of investment of the specimens (Zetalabor or Vipi Sil). The investment of specimens with Zetalabor silicone presented a greater surface hardness, independent of the type of disinfection and the period of storage. Based on these results, we suggest that the microhardness of the resin evaluated was not influenced by the method of disinfection or the time of storage used and was affected only by the investment material.

Cost-effectiveness of osteo-odonto keratoprosthesis in Singapore.

PubMed

Dong, Di; Tan, Anna; Mehta, Jodhbir S; Tan, Donald; Finkelstein, Eric Andrew

2014-01-01

To determine the long-term cost-effectiveness of osteo-odonto keratoprosthesis (OOKP) relative to no treatment among patients with end-stage corneal and ocular surface diseases in Singapore. Cost-effectiveness analysis based on data from a retrospective cohort study. From a health system perspective, we calculated the incremental cost-effectiveness ratio of OOKP treatment relative to no treatment over a 30-year horizon, based on data from a cohort of 23 patients who underwent OOKP surgery between 2004 and 2009 at Singapore National Eye Centre. Preoperative and postoperative vision-related quality-of-life values were estimated from patients' visual outcomes and were used to calculate the gain in quality-adjusted life years (QALYs) resulting from OOKP treatment. Unsubsidized costs for surgery, consultations, examinations, medications, follow-up visits, and treatments for complications were retrieved from patients' bills to estimate the total costs associated with OOKP treatment. Sensitivity analyses were conducted to test the robustness of the model. Over a 30-year period, OOKP treatment, compared with no treatment, improved QALYs by 3.991 among patients with end-stage corneal and ocular surface diseases at an additional cost of S$67 840 (US$55 150), resulting in an incremental cost-effectiveness ratio of S$17 000/QALY (US$13 820/QALY). Based on commonly cited cost-effectiveness benchmarks, the OOKP is a cost-effective treatment for patients with end-stage corneal and ocular surface diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Association of IL-21 cytokine with severity of primary Sjögren syndrome dry eye.

PubMed

Lim, Sung A; Nam, Doo Hyun; Lee, Jee Hye; Kwok, Seung-Ki; Park, Sung-Hwan; Chung, So-Hyang

2015-03-01

IL-21 plays an important role in primary Sjögren syndrome (SS) pathogenesis. The purpose of this study was to evaluate IL-21 expression in tears and the conjunctiva and to analyze the impact of IL-21 on primary SS dry eyes. Eighty subjects were enrolled in this study: 30 patients with primary SS dry eye (30 eyes); 30 patients with non-SS dry eye (30 eyes), and 20 normal controls. Tear IL-21 levels were measured by flow cytometry, and IL-21 gene expression in the conjunctiva from impression cytology was evaluated by quantitative polymerase chain reaction. Ocular Surface Disease Index, tear film breakup time, Schirmer I test, and ocular surface staining scores were obtained for all patients. Primary SS dry eyes had significantly higher tear IL-21 levels than non-SS dry eyes and normal controls (P < 0.01). In addition, IL-21 gene expression in the conjunctiva was also higher in primary SS dry eyes than in non-SS dry eyes and normal controls (P < 0.01). However, there were no significant differences in IL-21 expression in tears and the conjunctiva between non-SS dry eyes and controls. The tear IL-21 level was significantly correlated with ocular surface stain scores (r = 0.54, P < 0.01) and Schirmer I test values (r = -0.23, P < 0.05) in primary SS dry eyes. Our findings suggest that severity of primary SS dry eye is associated with IL-21.