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

Ocular ultrasonography focused on the posterior eye segment: what radiologists should know.

PubMed

De La Hoz Polo, Marcela; Torramilans Lluís, Anna; Pozuelo Segura, Oscar; Anguera Bosque, Albert; Esmerado Appiani, Catalina; Caminal Mitjana, Josep Maria

2016-06-01

Ocular B-mode ultrasonography (US) is an important adjuvant for the clinical assessment of a variety of ocular diseases. When ophthalmoscopy is not possible, mainly due to opacification of the transparent media (e.g., mature cataract or vitreous haemorrhage), US can guide the ophthalmologist in diagnosing disease and choosing treatment. The superficial location and cystic structure of the eye make US ideal for imaging of the eye. Moreover, dynamic study helps distinguish between various conditions that would otherwise be difficult to differentiate in some clinical setting, such as vitreous, retinal, and choroidal detachment. US is also good technique for detecting other pathologic conditions such as lens dislocation, vitreous haemorrhage, asteroid hyalosis, optic disc drusen, and tumors (e.g., choroidal melanoma, metastases, hemangioma). An understanding of the basic anatomy of the eye, the US technique, and common entities that affect the ocular globe will allow radiologists to offer this valuable imaging modality to patients and referring clinicians. This article focuses on the US anatomy and pathologic conditions that affect the posterior ocular segment. • US is specially indicated when ocular fundus cannot be assessed on ophthalmoscopy. • Multipurpose equipment with high-frequency transducers is optimal for imaging the eye. • Ultrasound can reliably depict ocular anatomy and pathology as detachments and tumours. • Dynamic examination is vital for distinguishing certain pathologic conditions as detachments.

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.

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.

Screening athletes with Down syndrome for ocular disease.

PubMed

Gutstein, Walter; Sinclair, Stephen H; North, Rachel V; Bekiroglu, N

2010-02-01

Persons with Down syndrome are well known to have a high prevalence of vision and eye health problems, many of which are undetected or untreated primarily because of infrequent ocular examinations. Public screening programs, directed toward the pediatric population, have become more popular and commonly use letter or symbol charts. This study compares 2 vision screening methods, the Lea Symbol chart and a newly developed interactive computer program, the Vimetrics Central Vision Analyzer (CVA), in their ability to identify ocular disease in the Down syndrome population. Athletes with Down syndrome participating in the European Special Olympics underwent an ocular screening including history, auto-refraction, colour vision assessment, stereopsis assessment, motility assessment, pupil reactivity, and tonometry testing, as well as anterior segment and fundus examinations to evaluate for ocular disease. Visual acuity was tested with the Lea chart and CVA to evaluate these as screening tests for detecting ocular disease as well as significant, uncorrected refractive errors. Among the 91 athletes that presented to the screening, 79 (158 eyes) were sufficiently cooperative for the examination to be completed. Mean age was 26 years +/-10.8 SD. Significant, uncorrected refractive errors (>/=1.00 spherical equivalent) were detected in 28 (18%) eyes and ocular pathology in 51 (32%) eyes. The Lea chart sensitivity and specificity were 43% and 74%, respectively, for detecting ocular pathology and 58% and 100% for detecting uncorrected refractive errors. The CVA sensitivity and specificity were 70% and 86% for detecting pathology and 71% and 100% for detecting uncorrected refractive errors. This study confirmed the findings of prior studies in identifying a significant presence of uncorrected refractive errors and ocular pathology in the Down syndrome population. Screening with the Lea symbol chart found borderline sufficient sensitivity and specificity for the test to be used for screening in this population. The better sensitivity and specificity of the CVA, if adjusted normative values are utilized, appear to make this test sufficient for testing Down syndrome children for identifying both refractive errors and ocular pathology. Copyright 2010 American Optometric Association. Published by Elsevier Inc. All rights reserved.

Ocular growth in the fetus. 1. Comparative study of axial length and biometric parameters in the fetus.

PubMed

Denis, D; Righini, M; Scheiner, C; Volot, F; Boubli, L; Dezard, X; Vola, J; Saracco, J B

1993-01-01

The knowledge of ocular growth during fetal life, when compared with other fetal biometric parameters, could not only provide a better definition of malformation syndromes but could also give a better understanding of certain pathological processes in premature babies and in newborns. As the literature concerning prenatal ocular dimensions contains few data, the aim of this study was to measure the axial length of the globe (AL) in fetuses and compare this measurement with their gestational age, weight, height, head circumference (HC) and thoracic circumference (TC) in order to compile a reference table. In the present study, 76 globes from 38 fetuses (18-41 weeks gestational age) from the Department of Pathology (Timone University Hospital, Marseille) were examined. Ultrasonography A and B were used to measure the AL, and a pathological examination determined fetal weight, HC, TC and height. We were interested to find out which of the parameters studied would give the best correlation with ocular growth. Statistical analysis showed that HC remained the most discriminant factor and correlated best with ocular growth. We thus obtained an equation for ocular size according to HC that could serve as a basis for detecting pre- or postnatal ocular defects.

[Nasal NK/T cell lymphoma with outstanding performance of ocular symptoms].

PubMed

Liu, Lei; Zhao, Yulin; Wang, Jia; Ma, Fei

2012-09-01

To investigate the clinical features and misdiagnosis of nasal NK/T cell lymphoma with outstanding performance in ocular symptoms. Clinical data of 11 patients who had nasal NK/T cell lymphoma with the outstanding performances in ocular symptoms during 2009 to 2011 were retrospectively analyzed. The rate of misdiagnosis in the first diagnosis and first pathological diagnosis were 72.7% and 27.3% respectively. Nasal NK/T cell lymphoma with obvious ocular symptoms developed quickly and had almost special imaging findings. Nasal NK/T cell lymphoma with outstanding performance of ocular symptoms can be easily misdiagnosed. Comprehensive consideration of the clinical features, imaging findings and pathological examination do help to make accurate diagnosis early.

Functional and Morphologic Changes of Meibomian Glands in an Asymptomatic Adult Population.

PubMed

Yeotikar, Nisha S; Zhu, Hua; Markoulli, Maria; Nichols, Kelly K; Naduvilath, Thomas; Papas, Eric B

2016-08-01

The aim of the study was to understand natural changes of meibomian glands (MG) that occur with aging in the absence of any ocular pathology or ocular discomfort symptoms, to differentiate between "age normal" and pathologic or dysfunctional changes of the MG. A total of 185 subjects (109 females) with no pre-existing ocular and systemic abnormalities were recruited and divided into four age groups: 25 to 34, 35 to 44, 45 to 54, and 55 to 66 years. At a single visit, the following MG measures were collected: meibum quality (MQ) and MG expressibility (MGE) of the lower lid, and MG drop-out score (meiboscale) using infrared meibography of the upper and lower lids. Assessments of anterior eye, tear function variables, noninvasive and invasive tear breakup time (TBUT), corneal integrity, and lid wiper epitheliopathy were also performed during the visit. An Ocular Surface Disease Index (OSDI) questionnaire was used to record dry eye symptoms. Meibum lipids samples were collected and analyzed. A majority of the study population (61%) was asymptomatic. There was a significant worsening in the MQ (P< 0.048), MGE (P < 0.03), and meiboscale (P < 0.01) with increasing age. Significant increase was observed in anterior blepharitis (P < 0.001) and telangiectasia (P< 0.02) with aging. Interestingly, tear osmolarity decreased significantly (P < 0.001), while tear meniscus height (P < 0.001) and invasive TBUT (P = 0.02) increased with increase in age. There was no significant association between MG variables and sex, ocular discomfort symptoms, or meibum lipids classes. Progressive MG loss occurs normally with age accompanied by reduced quality and quantity of the meibum produced. However, clinical presentation of ocular discomfort symptoms is stalled without corresponding disruption to tear function.

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.

Canine, feline, and equine corneal vascular neoplasia: A retrospective study (2007-2015).

PubMed

Shank, Alba Maria M; Teixeria, Leandro B C; Dubielzig, Richard R

2018-04-24

Corneal vascular neoplasms (hemangioma and hemangiosarcoma) are rare in all species. Reported cases are single case reports in a single species. Archived cases of corneal hemangioma and hemangiosarcoma from dogs, cats, and horses were obtained from the Comparative Ocular Pathology Lab of Wisconsin (COPLOW, Madison, WI), tabulated, and examined. This retrospective study describes the breeds, ages, tumor types, and characteristics of vascular neoplasms that appeared to be primarily corneal in location, in feline, canine, and equine patients, with gross and histologic images. There is a discussion of predisposing factors and speculated association with chronic ocular surface disease. © 2018 American College of Veterinary Ophthalmologists.

Differential protein expression in tears of patients with primary open angle and pseudoexfoliative glaucoma.

PubMed

Pieragostino, Damiana; Bucci, Sonia; Agnifili, Luca; Fasanella, Vincenzo; D'Aguanno, Simona; Mastropasqua, Alessandra; Ciancaglini, Marco; Mastropasqua, Leonardo; Di Ilio, Carmine; Sacchetta, Paolo; Urbani, Andrea; Del Boccio, Piero

2012-04-01

Primary open angle (POAG) and pseudoexfoliative glaucoma (PXG) are the most common primary and secondary forms of glaucoma, respectively. Even though the patho-physiology, aqueous humor composition, risk factors, clinical features, therapy and drug induced ocular surface changes in POAG and PXG have been widely studied, to date information concerning tear protein characterization is lacking. Tears are a source of nourishment for ocular surface tissues and a vehicle to remove local waste products, metabolized drugs and inflammatory mediators produced in several ophthalmic diseases. In glaucoma, the proteomic definition of tears may provide insights concerning patho-physiology of the disease and ocular surface modifications induced by topical therapy. Our study aimed at characterizing protein patterns in tears of patients with medically controlled POAG and PXG. A comparative tears proteomic analysis by label-free LC-MS(E) highlighted differences in the expression of several proteins in the two glaucoma sub-types and control subjects, highlighting inflammation pathways expressed in both diseases. Results were independently reconfirmed by SDS-PAGE and linear MALDI-TOF MS, validating altered levels of Lysozyme C, Lipocalin-1, Protein S100, Immunoglobulins and Prolactin Inducible Protein. Moreover, we found a differential pattern of phosphorylated Cystatin-S that distinguishes the two pathologies. The most relevant results suggest that in both pathologies there may be active inflammation pathways related to the disease and/or induced by therapy. We show, for the first time, tear protein patterns expressed under controlled intraocular pressure conditions in POAG and PXG subjects. These findings could help in the understanding of molecular machinery underlying these ophthalmologic diseases, resulting in early diagnosis and more specific therapy.

Ophthalmic pathology of Nance-Horan syndrome: case report and review of the literature.

PubMed

Ding, Xiaoyan; Patel, Mrinali; Herzlich, Alexandra A; Sieving, Pamela C; Chan, Chi-Chao

2009-09-01

Nance-Horan syndrome (NHS) is a rare X-linked disorder typified by dense congenital central cataracts, microcornea, anteverted and simplex pinnae, brachymetacarpalia, and numerous dental anomalies due in most cases to a mutation in the NHS gene. We present a case of clinical manifestation and ocular pathology in a patient with NHS. This article also reviews and discusses the relevant literature. Classic and novel ocular pathological findings of a young male with NHS are described, including congenital cataracts, infantile glaucoma, scleral staphyloma, and severe retinal cystoid degeneration. We report a new pathological finding of severe retinal cystoid degeneration in this NHS patient and confirm abnormal development of the anterior chamber angle structure. These findings, coupled with our analysis of the available NHS literature, provide new understanding of the histopathological basis of ocular abnormalities and vision loss in NHS.

Murine neonatal infection provides an efficient model for congenital ocular toxoplasmosis.

PubMed

Lahmar, Ibtissem; Guinard, Marie; Sauer, Arnaud; Marcellin, Luc; Abdelrahman, Tamer; Roux, Michel; Mousli, Marc; Moussa, Adnan; Babba, Hamouda; Pfaff, Alexander W; Candolfi, Ermanno

2010-02-01

Congenital infection is one of the most serious settings of infection with the apicomplexan parasite Toxoplasma gondii. Ocular diseases, such as retinochoroiditis, are the most common sequels of such infection in utero. However, while numerous studies have investigated the physiopathology of acquired toxoplasmosis, congenital infection has been largely neglected so far. Here, we establish a mouse model of congenital ocular toxoplasmosis. Parasite load and ocular pathology have been followed for the first 4 weeks of life. Ocular infection developed slowly compared to cerebral infection. Even after 4 weeks, not all eyes were infected and ocular parasite load was low. Therefore, we evaluated a scheme of neonatal infection to overcome problems associated with congenital infection. Development of infection and physiopathology was similar, but at a higher, more reliable rate. In summary, we have established a valuable model of neonatal ocular toxoplasmosis, which facilitates the research of the underlying physiopathological mechanisms and new diagnostic approaches of this pathology. Copyright 2009 Elsevier Inc. All rights reserved.

Animal models of ocular angiogenesis: from development to pathologies.

PubMed

Liu, Chi-Hsiu; Wang, Zhongxiao; Sun, Ye; Chen, Jing

2017-11-01

Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, as well as corneal diseases with abnormal angiogenesis. Development of reproducible and reliable animal models of ocular angiogenesis has advanced our understanding of both the normal development and the pathobiology of ocular neovascularization. These models have also proven to be valuable experimental tools with which to easily evaluate potential antiangiogenic therapies beyond eye research. This review summarizes the current available animal models of ocular angiogenesis. Models of retinal and choroidal angiogenesis, including oxygen-induced retinopathy, laser-induced choroidal neovascularization, and transgenic mouse models with deficient or spontaneous retinal/choroidal neovascularization, as well as models with induced corneal angiogenesis, are widely used to investigate the molecular and cellular basis of angiogenic mechanisms. Theoretical concepts and experimental protocols of these models are outlined, as well as their advantages and potential limitations, which may help researchers choose the most suitable models for their investigative work.-Liu, C.-H., Wang, Z., Sun, Y., Chen, J. Animal models of ocular angiogenesis: from development to pathologies. © FASEB.

Endothelial TWIST1 Promotes Pathological Ocular Angiogenesis

PubMed Central

Li, Jie; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Fu, Zhongjie; Evans, Lucy P.; Tian, Katherine T.; Juan, Aimee M.; Hurst, Christian G.; Mammoto, Akiko; Chen, Jing

2014-01-01

Purpose. Pathological neovessel formation impacts many blinding vascular eye diseases. Identification of molecular signatures distinguishing pathological neovascularization from normal quiescent vessels is critical for developing new interventions. Twist-related protein 1 (TWIST1) is a transcription factor important in tumor and pulmonary angiogenesis. This study investigated the potential role of TWIST1 in modulating pathological ocular angiogenesis in mice. Methods. Twist1 expression and localization were analyzed in a mouse model of oxygen-induced retinopathy (OIR). Pathological ocular angiogenesis in Tie2-driven conditional Twist1 knockout mice were evaluated in both OIR and laser-induced choroidal neovascularization models. In addition, the effects of TWIST1 on angiogenesis and endothelial cell function were analyzed in sprouting assays of aortic rings and choroidal explants isolated from Twist1 knockout mice, and in human retinal microvascular endothelial cells treated with TWIST1 small interfering RNA (siRNA). Results. TWIST1 is highly enriched in pathological neovessels in OIR retinas. Conditional Tie2-driven depletion of Twist1 significantly suppressed pathological neovessels in OIR without impacting developmental retinal angiogenesis. In a laser-induced choroidal neovascularization model, Twist1 deficiency also resulted in significantly smaller lesions with decreased vascular leakage. In addition, loss of Twist1 significantly decreased vascular sprouting in both aortic ring and choroid explants. Knockdown of TWIST1 in endothelial cells led to dampened expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased endothelial cell proliferation. Conclusions. Our study suggests that TWIST1 is a novel regulator of pathologic ocular angiogenesis and may represent a new molecular target for developing potential therapeutic treatments to suppress pathological neovascularization in vascular eye diseases. PMID:25414194

Ophthalmic Pathology of Nance-Horan Syndrome: Case Report and Review of the Literature

PubMed Central

Ding, Xiaoyan; Patel, Mrinali; Herzlich, Alexandra A.; Sieving, Pamela C.; Chan, Chi-Chao

2009-01-01

Background Nance-Horan syndrome (NHS) is a rare X-linked disorder typified by dense congenital central cataracts, microcornea, anteverted and simplex pinnae, brachymetacarpalia, and numerous dental anomalies due in most cases to a mutation in the NHS gene. Material and Methods We present a case of clinical manifestation and ocular pathology in a patient with NHS. This article also reviews and discusses the relevant literature. Results Classic and novel ocular pathological findings of a young male with NHS are described, including congenital cataracts, infantile glaucoma, scleral staphyloma, and severe retinal cystoid degeneration. Conclusions We report a new pathological finding of severe retinal cystoid degeneration in this NHS patient and confirm abnormal development of the anterior chamber angle structure. These findings, coupled with our analysis of the available NHS literature, provide new understanding of the histopathological basis of ocular abnormalities and vision loss in NHS. PMID:19941417

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

Accuracy of vision technicians in screening ocular pathology at rural vision centres of southern India.

PubMed

Suram, Vasantha; Addepalli, Uday Kumar; Krishnaiah, Sannapaneni; Kovai, Vilas; Khanna, Rohit C

2016-03-01

There is paucity of data on the inter-observer agreement and diagnostic accuracy between a primary-care technician (vision technician) and an ophthalmologist. Hence, the current study was conducted to assess the accuracy of vision technicians, to screen potentially sight-threatening ocular conditions at rural vision centres of southern India and their agreement with an ophthalmologist. In July to August 2010, patients presenting to seven vision centres in Adilabad district (Andhra Pradesh) were selected and screened in a masked manner by seven vision technicians followed by an examination by a consultant ophthalmologist. Agreement was assessed between vision technicians and the ophthalmologist for screening of potential sight-threatening ocular conditions and decisions for referral. The ophthalmologist's findings were considered as the reference standard. Two hundred and seventy-nine patients were enrolled at seven vision centres with a mean age of 32.9 ± 21.8 years. Agreement for screening of ocular pathology was 0.82 (95 per cent CI, 0.8-0.83). There was excellent agreement for cataract (0.97; 95 per cent CI, 0.93-1), refractive error (0.98; 95 per cent CI, 0.96-1), corneal pathology (1.0; 95 per cent CI, 1.0-1.0) and other anterior segment pathology (0.95; 95 per cent CI, 0.9-1); the agreement was moderate to fair for detection of glaucoma suspects (0.43; 95 per cent CI, 0.28-0.60) and retinal pathology (0.39; 95 per cent CI, 0.14-0.63). Sensitivity for screening of anterior segment pathology was 94.6-100 per cent. There was a fair to moderate sensitivity for glaucoma suspect; 35.6 per cent (95 per cent CI, 21.9-51.2) and retinal pathology 26.3 per cent (95 per cent CI, 9.2-51.2). Specificity for screening of ocular pathology was 98.2 to 100 per cent. The kappa (κ) agreement for referral for any pathology was 0.82 (0.8-0.83) CONCLUSION: As there is good agreement between the vision technicians and the ophthalmologist for screening and referral of anterior segment pathology but moderate to fair for glaucoma suspects and retinal pathology, vision technicians would be a good resource at the primary level to screen for anterior segment pathology; however, they may need further training to detect posterior segment pathology. © 2016 Optometry Australia.

The ocular pathology of Norrie disease in a fetus of 11 weeks' gestational age.

PubMed

Parsons, M A; Curtis, D; Blank, C E; Hughes, H N; McCartney, A C

1992-01-01

The ocular pathology of Norrie disease was studied for the first time in a fetus of 11 weeks' gestation, following prenatal diagnosis using genetic markers for Norrie disease and elective abortion. The eyes were histologically normal, with no evidence of primary neuroectodermal maldevelopment of the retina, previously postulated to be the cause of the ocular changes. We believe that the retinal and other manifestations of Norrie disease are the result of a primary abnormality of vascular proliferation, probably in relation to persistent hyperplastic primary vitreous after approximately 14 weeks' gestation. We postulate that the ocular and otological effects of Norrie disease may be due to a genetically mediated abnormality of secretion of, or sensitivity to, angiogenic growth factors at endodermal-neuroectodermal interfaces during fetal and postnatal development.

Ophthalmic Manifestations and Histopathology of Xeroderma Pigmentosum: Two Clinicopathological Cases and a Review of the Literature

PubMed Central

Ramkumar, Hema L.; Brooks, Brian P.; Cao, Xiaoguang; Tamura, Deborah; DiGiovanna, John J.; Kraemer, Kenneth H.; Chan, Chi-Chao

2011-01-01

Xeroderma pigmentosum is a rare, autosomal recessive disease caused by a defect in DNA repair. Patients with xeroderma pigmentosum often have cutaneous and ocular sun sensitivity, freckle-like skin pigmentation, multiple skin and eye cancers, and, in some patients, progressive neurodegeneration. Xeroderma pigmentosum predominantly affects the UV exposed ocular surface, resulting in eyelid atrophy and cancers, corneal dryness, exposure keratopathy, and conjunctival tumors. We report the clinical history and ocular pathology of two Caucasian women who had xeroderma pigmentosum with neurological degeneration: Case 1, who died at age 44 and Case 2, who died at age 45. Case 1 with mutations in the XPA gene, had more than 180 basal cell carcinomas of her skin and eyelids and died from complications of neurodegeneration. Case 2, with mutations in the XPD gene, was sun protected and had 3 skin cancers. She died from complications of neurodegeneration and pneumonia. Both patients had bilateral pinguecula, corneal pannus and exposure keratopathy. Case 1 had bilateral optic atrophy, while Case 2 had bilateral peripheral retinal pigmentary degeneration. Both patients developed retinal gliosis. The ophthalmic manifestations and pathology of xeroderma pigmentosum are discussed and reviewed with respect to this report and other cases in the literature. These cases illustrate the role of DNA repair in protection of the eyes from UV damage and neurodegeneration of the retina. PMID:21684361

Ophthalmic manifestations and histopathology of xeroderma pigmentosum: two clinicopathological cases and a review of the literature.

PubMed

Ramkumar, Hema L; Brooks, Brian P; Cao, Xiaoguang; Tamura, Deborah; Digiovanna, John J; Kraemer, Kenneth H; Chan, Chi-Chao

2011-01-01

Xeroderma pigmentosum is a rare, autosomal recessive disease caused by a defect in DNA repair. Patients with xeroderma pigmentosum often have cutaneous and ocular sun sensitivity, freckle-like skin pigmentation, multiple skin and eye cancers, and, in some patients, progressive neurodegeneration. Xeroderma pigmentosum predominantly affects the ultraviolet (UV) exposed ocular surface, resulting in eyelid atrophy and cancers, corneal dryness, exposure keratopathy, and conjunctival tumors. We report the clinical history and ocular pathology of two white women who had xeroderma pigmentosum with neurological degeneration: Case 1 (died at age 44 years) and Case 2 (died at age 45 years). Case 1, with mutations in the XPA gene, had more than 180 basal cell carcinomas of her skin and eyelids and died from complications of neurodegeneration. Case 2, with mutations in the XPD gene, was sun-protected and had three skin cancers. She died from complications of neurodegeneration and pneumonia. Both patients had bilateral pinguecula, corneal pannus, and exposure keratopathy. Case 1 had bilateral optic atrophy, and Case 2 had bilateral peripheral retinal pigmentary degeneration. Both patients developed retinal gliosis. The ophthalmic manifestations and pathology of xeroderma pigmentosum are discussed and reviewed with respect to this report and other cases in the literature. These cases illustrate the role of DNA repair in protection of the eyes from UV damage and neurodegeneration of the retina. Published by Elsevier Inc.

Ocular Surface and Tear Film Changes in Older Women Working with Computers.

PubMed

Ribelles, Alfredo; Galbis-Estrada, Carmen; Parras, Maria A; Vivar-Llopis, Bárbara; Marco-Ramírez, Carla; Diaz-Llopis, Manuel

2015-01-01

The aim of this work is to investigate changes in the ocular surface (OS) and tear film (TF) by means of questionnaire-based subjective symptoms, TF break-up time, Schirmer test, and TF analysis in women working with computers and to analyze the effects of the oral supplementation with antioxidants/omega 3 fatty acids (A/ω3) in the OS outcomes. Women aged 40-65 years (n = 148) were recruited at the Administrative Offices of Valencia (Spain) and distributed into two age groups, 40-52 years (AGE1; n = 87) and 53-65 years (AGE2; n = 61), and then subdivided according to being (or not) computer users (CUG; NCUG) during the workday. Homogeneous subgroups were randomly assigned (or not) to the daily intake of three pills of A/ω3 for three months. At baseline and at the end of follow-up, personalized interviews and ocular examination were done. Reflex tear samples were collected from the inferior meniscus and processed for a multiplexed particle-based flow cytometry assay to measure proinflammatory molecules. Statistics were performed using the SPSS 15.0 program. The OS pathology was clinically evident in the AGE1-CUG (33%) versus the AGE2-CUG (64%) of women. Significantly higher interleukins-1β and -6 tear levels were found in the AGE1 versus the AGE2 women employees (P = 0.006 and P = 0.001, resp.), as well as in the CUG versus the NCUG (P = 0.001 and P = 0.000, resp.). Supplementation with A/ω3 positively influenced the OS pathology as manifested by the amelioration of the clinical signs/symptoms related to computer uses. Strategies involving a safe environment and oral micronutrient supplements may be managed within eye-care standards in older women.

Ocular Surface and Tear Film Changes in Older Women Working with Computers

PubMed Central

Ribelles, Alfredo; Parras, Maria A.; Vivar-Llopis, Bárbara; Marco-Ramírez, Carla; Diaz-Llopis, Manuel

2015-01-01

The aim of this work is to investigate changes in the ocular surface (OS) and tear film (TF) by means of questionnaire-based subjective symptoms, TF break-up time, Schirmer test, and TF analysis in women working with computers and to analyze the effects of the oral supplementation with antioxidants/omega 3 fatty acids (A/ω3) in the OS outcomes. Women aged 40–65 years (n = 148) were recruited at the Administrative Offices of Valencia (Spain) and distributed into two age groups, 40–52 years (AGE1; n = 87) and 53–65 years (AGE2; n = 61), and then subdivided according to being (or not) computer users (CUG; NCUG) during the workday. Homogeneous subgroups were randomly assigned (or not) to the daily intake of three pills of A/ω3 for three months. At baseline and at the end of follow-up, personalized interviews and ocular examination were done. Reflex tear samples were collected from the inferior meniscus and processed for a multiplexed particle-based flow cytometry assay to measure proinflammatory molecules. Statistics were performed using the SPSS 15.0 program. The OS pathology was clinically evident in the AGE1-CUG (33%) versus the AGE2-CUG (64%) of women. Significantly higher interleukins-1β and -6 tear levels were found in the AGE1 versus the AGE2 women employees (P = 0.006 and P = 0.001, resp.), as well as in the CUG versus the NCUG (P = 0.001 and P = 0.000, resp.). Supplementation with A/ω3 positively influenced the OS pathology as manifested by the amelioration of the clinical signs/symptoms related to computer uses. Strategies involving a safe environment and oral micronutrient supplements may be managed within eye-care standards in older women. PMID:26557673

Putting vital stains in context.

PubMed

Efron, Nathan

2013-07-01

While vital staining remains a cornerstone in the diagnosis of ocular disease and contact lens complications, there are many misconceptions regarding the properties of commonly used dyes by eye-care practitioners and what is and what is not corneal staining after instillation of sodium fluorescein. Similarly, the proper use and diagnostic utility of rose Bengal and lissamine green B, the other two ophthalmic dyes commonly used for assessing ocular complications, have similarly remained unclear. Due to the limitations of vital stains for definitive diagnosis, concomitant signs and symptoms in addition to a complete patient history are required. Over the past decade, there have been many reports of a type of corneal staining--often referred to as solution-induced corneal staining (SICS)--that is observed with the use of multipurpose solutions in combination with soft lenses, more specifically silicone hydrogel lenses. Some authors believe that SICS is a sign of lens/solution incompatibility; however, new research shows that SICS may be neither a measure of lens/solution biocompatibility nor 'true' corneal staining, as that observed in pathological situations. A large component of SICS may be a benign phenomenon, known as preservative-associated transient hyperfluorescence (PATH). There is a lack of correlated signs and/or symptoms with SICS/PATH. Several properties of SICS/PATH, such as appearance and duration, differentiate it from pathological corneal staining. This paper reviews the properties of vital stains, their use and limitations in assessment of the ocular surface, the aetiology of corneal staining, characteristics of SICS/PATH that differentiate it from pathological corneal staining and what the SICS/PATH phenomenon means for contact lens-wearing patients. © 2012 The Author. Clinical and Experimental Optometry © 2012 Optometrists Association Australia.

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

Albinism: Particular Attention to the Ocular Motor System

PubMed Central

Hertle, Richard W.

2013-01-01

The purpose of this report is to summarize an understanding of the ocular motor system in patients with albinism. Other than the association of vertical eccentric gaze null positions and asymmetric, (a) periodic alternating nystagmus in a large percentage of patients, the ocular motor system in human albinism does not contain unique pathology, rather has “typical” types of infantile ocular oscillations and binocular disorders. Both the ocular motor and afferent visual system are affected to varying degrees in patients with albinism, thus, combined treatment of both systems will maximize visual function. PMID:24014991

The Significance of the Discordant Occurrence of Lens Tumors in Humans versus Other Species

PubMed Central

Albert, Daniel M.; Phelps, Paul O.; Surapaneni, Krishna R.; Thuro, Bradley A.; Potter, Heather D.; Ikeda, Akihiro; Teixeira, Leandro B. C.; Dubielzig, Richard R.

2015-01-01

Purpose The purpose of this study was to determine in which species and under what conditions lens tumors occur. Design A review of data bases of available human and veterinary ocular pathological material and the previously reported literature. Participants Approximately 18,000 patients who had ocular surgical specimens submitted and studied at the University of Wisconsin School of Medicine and Public Health (UWSMPH) between 1920 and 2014 and 45,000 ocular veterinary cases from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) between 1983 and 2014. Methods Material in two major archived collections at the University of Wisconsin medical and veterinary schools were studied for occurrence of lens tumors. Tumor was defined as “a new growth of tissue characterized by progressive, uncontrolled proliferation of cells.” In addition, cases presented at 3 major eye pathology societies (Verhoeff-Zimmerman Ophthalmic Pathology Society, Eastern Ophthalmic Pathology Society, and The Armed Forces Institute of Pathology Ophthalmic Alumni Society) from 1975 through 2014 were reviewed. Finally, a careful search of the literature was carried out. Approval from the IRB to carry out this study was obtained. Main Outcome Measures The presence of tumors of the lens. Results The database search and literature review failed to find an example of a lens tumor in humans. In contrast, examples of naturally occurring lens tumors were found in cats, dogs, rabbits, and birds. 4.5% of feline intraocular and adnexal neoplasms (234/5153) in the veterinary school database were designated as feline ocular post-traumatic sarcoma (FOPTS), a tumor previously demonstrated to be of lens epithelial origin. Similar tumors were seen in rabbit eyes, a bird, and in a dog. All four species with lens tumors had a history of either ocular trauma or protracted uveitis. The literature search also revealed cases where lens tumors were induced in zebrafish, rainbow trout, hamsters, and mice, by carcinogenic agents (methylcholanthrene, thioacetamide), oncogenic viruses (SV40, HPV-16), and genetic manipulation. Conclusions Our results suggest that lens tumors do not occur in humans. In contrast, following lens capsule rupture, a lens tumor can occur in other species. We hypothesize that a genetic mechanism exists which prevents lens tumors in humans. PMID:26130328

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

Ultrasound and MRI of Pediatric Ocular Masses with Histopathologic Correlation

PubMed Central

Brennan, Rachel C.; Wilson, Matthew W.; Kaste, Sue; Helton, Kathleen J.; McCarville, M. Beth

2012-01-01

We review our experience with unusual ocular pathologies mimicking retinoblastoma that were referred to our institution over the past two decades. After presenting the imaging anatomy of the normal eye, we discuss pertinent clinical and pathological features, and illustrate the ultrasound and magnetic resonance imaging appearance of retinoblastoma, medulloepithelioma, uveal melanoma, persistent fetal vasculature, Coats disease, corneal dermoid, retinal dysplasia and toxocara granuloma. Features useful in discriminating between these entities are emphasized. PMID:22466750

Fundus autofluorescence imaging in an ocular screening program.

PubMed

Kolomeyer, A M; Nayak, N V; Szirth, B C; Khouri, A S

2012-01-01

Purpose. To describe integration of fundus autofluorescence (FAF) imaging into an ocular screening program. Methods. Fifty consecutive screening participants were included in this prospective pilot imaging study. Color and FAF (530/640 nm exciter/barrier filters) images were obtained with a 15.1MP Canon nonmydriatic hybrid camera. A clinician evaluated the images on site to determine need for referral. Visual acuity (VA), intraocular pressure (IOP), and ocular pathology detected by color fundus and FAF imaging modalities were recorded. Results. Mean ± SD age was 47.4 ± 17.3 years. Fifty-two percent were female and 58% African American. Twenty-seven percent had a comprehensive ocular examination within the past year. Mean VA was 20/39 in the right eye and 20/40 in the left eye. Mean IOP was 15 mmHg bilaterally. Positive color and/or FAF findings were identified in nine (18%) individuals with diabetic retinopathy or macular edema (n = 4), focal RPE defects (n = 2), age-related macular degeneration (n = 1), central serous retinopathy (n = 1), and ocular trauma (n = 1). Conclusions. FAF was successfully integrated in our ocular screening program and aided in the identification of ocular pathology. Larger studies examining the utility of this technology in screening programs may be warranted.

Fundus Autofluorescence Imaging in an Ocular Screening Program

PubMed Central

Kolomeyer, A. M.; Nayak, N. V.; Szirth, B. C.; Khouri, A. S.

2012-01-01

Purpose. To describe integration of fundus autofluorescence (FAF) imaging into an ocular screening program. Methods. Fifty consecutive screening participants were included in this prospective pilot imaging study. Color and FAF (530/640 nm exciter/barrier filters) images were obtained with a 15.1MP Canon nonmydriatic hybrid camera. A clinician evaluated the images on site to determine need for referral. Visual acuity (VA), intraocular pressure (IOP), and ocular pathology detected by color fundus and FAF imaging modalities were recorded. Results. Mean ± SD age was 47.4 ± 17.3 years. Fifty-two percent were female and 58% African American. Twenty-seven percent had a comprehensive ocular examination within the past year. Mean VA was 20/39 in the right eye and 20/40 in the left eye. Mean IOP was 15 mmHg bilaterally. Positive color and/or FAF findings were identified in nine (18%) individuals with diabetic retinopathy or macular edema (n = 4), focal RPE defects (n = 2), age-related macular degeneration (n = 1), central serous retinopathy (n = 1), and ocular trauma (n = 1). Conclusions. FAF was successfully integrated in our ocular screening program and aided in the identification of ocular pathology. Larger studies examining the utility of this technology in screening programs may be warranted. PMID:23316224

The prevalence of ocular diseases in polish Arabian horses.

PubMed

Paschalis-Trela, Katarzyna; Cywińska, Anna; Trela, Jan; Czopowicz, Michał; Kita, Jerzy; Witkowski, Lucjan

2017-11-07

Equine ocular diseases pose a medical challenge due to long-lasting and cost-consuming therapies as well as economic issues associated with potential decrease in value of affected horses. The scale of the problem is significant but difficult to precisely define because epidemiological data is limited and lacks consistency in presentation. To date, no retrospective studies specifically investigating Arabian horses have been published. The aim of this cross-sectional study was to investigate the prevalence of ocular lesions and define the ocular diseases present in Arabian horses from breeding farms in Poland. Clinical and ophthalmic examination of 615 Arabian horses at Polish breeding farms (15% of Arabian population in Poland) were performed and medical history from the previous 5 years was analyzed. Data was obtained from review of veterinary archives and epidemiological interview of the resident veterinarian at each farm. The prevalence of ocular diseases was 9.75%. The following pathologies were diagnosed (with their respective prevalence): equine recurrent uveitis (ERU; 5.5%); cataract not related to ERU (3.3%); non-visual eyes (1.13%); posttraumatic lesions (0.8%); glaucoma (0.16%). In this study, ERU was the most common ocular disease identified in Arabian horses in Poland. Its prevalence was lower than usually reported in Europe and the United States. There was no sex or farm predisposition but ocular disease prevalence increased with age. Other severe ocular pathologies were also observed, confirming that ocular diseases remain an important clinical problem.

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 ocular complications of boxing.

PubMed

Giovinazzo, V J; Yannuzzi, L A; Sorenson, J A; Delrowe, D J; Cambell, E A

1987-06-01

In cooperation with the New York State Athletic Commission, 74 boxers applying for a new or yearly renewal license were sequentially referred over a 2-year period for a complete dilated ocular examination at the Sports Vision Institute of the Manhattan Eye, Ear and Throat Hospital. At least one ocular injury was found in 66% of boxers. Vision-threatening injuries, defined as significant damage to the angle, lens, macula, or peripheral retina occurred in 58% of boxers. Nineteen percent of boxers had angle abnormalities. Nineteen percent of boxers had pathologic cataracts, over 70% of these were posterior subcapsular. Six boxers had macular lesions. A total of 24% of boxers had retinal tears. Standardized photographs were used to distinguish pathologic cataracts from congenital opacities and pathologic retinal tears from atrophic holes. Attempts were made to identify risk factors in boxing that might be predictive for ocular injury. Variables included age, weight division, left- or right-handedness, total number of losses, and total number of bouts. Significant correlations were found between the total number of bouts and the total number of losses, and the presence of retinal tears. College varsity athletes were selected as controls. Significant differences were found between boxers and controls for the total number of injuries, total vision-threatening injuries, and the number of retinal tears. A series of recommendations are proposed to aide in the early detection and prevention of serious ocular injuries.

The "demise" of diagnostic and research ocular pathology: temporary or forever?

PubMed

Apple, David J; Werner, Liliana; Mamalis, Nick; Olson, Randall J

2003-01-01

Several authorities have documented a significant decrease in support for modern eye pathology/pathology research laboratories. Indeed, many laboratories have closed or suffered marked cutbacks. The purpose of this report is to ask why this is so and to seek a possible means for reversing this trend. Observations from the senior author's experience and a case from author's facility are analyzed. There are several reasons for ocular pathologists' difficulties, such as financial problems, lack of vision, personality conflicts, and problems with the departmental administration. Until recently, most research and development in several subspecialty fields of ophthalmology, including biodevices research, has been done primarily by engineers and in-house workers in industry. This precludes proper independent, nonbiased control and guidance from academia. Most ocular pathologists have not participated in this relatively new and wide-open field. We suggest a new realm of activity for today's newly trained ocular pathologists. Based on personal experience of two decades of fruitful collaboration with industry, we believe that ocular pathologists are uniquely trained to apply their expertise to various new fields of research that most pathologists today have not utilized. An important example is research on clinicopathological aspects of implantable biodevices. In addition, support and oversight should be provided by the major ophthalmic societies, such as the American Academy of Ophthalmology, in order to retain (even regain) control over this field. This is mandatory in order to control the safety and efficacy of new drugs and devices being introduced almost daily. Only then can clear differentiation between profit and patient welfare be achieved as potentially dangerous devices and techniques are let loose on the market. The field of "routine, descriptive" eye pathology is severely wounded and will return only in an attenuated fashion. In general, full-time support for ocular pathologists will not be possible unless they seek extra support from the private sector, engage in a concurrent clinical practice, or are supported by an endowed chair (a wonderful alternative).

The "demise" of diagnostic and research ocular pathology: temporary or forever?

PubMed Central

Apple, David J; Werner, Liliana; Mamalis, Nick; Olson, Randall J

2003-01-01

PURPOSE: Several authorities have documented a significant decrease in support for modern eye pathology/pathology research laboratories. Indeed, many laboratories have closed or suffered marked cutbacks. The purpose of this report is to ask why this is so and to seek a possible means for reversing this trend. METHODS: Observations from the senior author's experience and a case from author's facility are analyzed. RESULTS: There are several reasons for ocular pathologists' difficulties, such as financial problems, lack of vision, personality conflicts, and problems with the departmental administration. Until recently, most research and development in several subspecialty fields of ophthalmology, including biodevices research, has been done primarily by engineers and in-house workers in industry. This precludes proper independent, nonbiased control and guidance from academia. Most ocular pathologists have not participated in this relatively new and wide-open field. CONCLUSIONS: We suggest a new realm of activity for today's newly trained ocular pathologists. Based on personal experience of two decades of fruitful collaboration with industry, we believe that ocular pathologists are uniquely trained to apply their expertise to various new fields of research that most pathologists today have not utilized. An important example is research on clinicopathological aspects of implantable biodevices. In addition, support and oversight should be provided by the major ophthalmic societies, such as the American Academy of Ophthalmology, in order to retain (even regain) control over this field. This is mandatory in order to control the safety and efficacy of new drugs and devices being introduced almost daily. Only then can clear differentiation between profit and patient welfare be achieved as potentially dangerous devices and techniques are let loose on the market. The field of "routine, descriptive" eye pathology is severely wounded and will return only in an attenuated fashion. In general, full-time support for ocular pathologists will not be possible unless they seek extra support from the private sector, engage in a concurrent clinical practice, or are supported by an endowed chair (a wonderful alternative). PMID:14971571

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.

The temperature-sensitive mutants of Toxoplasma gondii and ocular toxoplasmosis.

PubMed

Lu, Fangli; Huang, Shiguang; Kasper, Lloyd H

2009-01-22

The risk of blindness caused by ocular toxoplasmosis supports efforts to improve our understanding for control of this disease. In this study, the involvement of CD8(+), CD4(+), B cell, and IL-10 gene in the immune response of primary ocular infection with the temperature-sensitive mutant (ts-4) of the RH Toxoplasma gondii strain, and in the protective immunity of ocular ts-4 vaccination and challenge with RH strain was investigated in murine models utilizing inbred C57BL/6 mice-deficient in CD4(+), CD8(+), B cells (microMT), or IL-10 gene. Compared to naive mice, all WT and mutant mice had different degree of ocular pathological changes after ts-4 ocular infection, in which both CD8 KO and IL-10 KO mice showed the most severe ocular lesions. Immunized by ts-4 intracameral (i.c.) inoculation, all mutant mice had partially decreased vaccine-induced resistance associated with increased ocular parasite burdens after RH strain challenge. A significant increase of the percentages of B cells and CD8(+) T cells in the draining lymph nodes were observed in WT and IL-10 KO mice after either infection or challenge. The levels of specific anti-toxoplasma IgG in both eye fluid and serum from all the mice were significantly increased after ts-4 i.c. immunization, except microMT mice. These results suggest that the avirulent ts-4 of T. gondii inoculated intracamerally can induce both ocular pathology and ocular protective immunity; CD4(+), CD8(+), B cell, and IL-10 gene are all necessary to the vaccine-induced resistance to ocular challenge by virulent RH strain, in which CD8(+) T cells are the most important component.

Critical role of caveolin-1 in ocular neovascularization and multitargeted antiangiogenic effects of cavtratin via JNK

PubMed Central

Jiang, Yida; Lin, Xianchai; Tang, Zhongshu; Lee, Chunsik; Tian, Geng; Du, Yuxiang; Yin, Xiangke; Ren, Xiangrong; Huang, Lijuan; Ye, Zhimin; Chen, Wei; Zhang, Fan; Mi, Jia; Gao, Zhiqin; Wang, Shasha; Chen, Qishan; Xing, Liying; Wang, Bin; Cao, Yihai; Sessa, William C.; Ju, Rong; Liu, Yizhi; Li, Xuri

2017-01-01

Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization. Importantly, combined administration of cavtratin and anti–VEGF-A inhibited neovascularization more effectively than monotherapy, suggesting the existence of other pathways inhibited by cavtratin in addition to VEGF-A. Indeed, we found that cavtratin suppressed multiple critical components of pathological angiogenesis, including inflammation, permeability, PDGF-B and endothelial nitric oxide synthase expression (eNOS). Mechanistically, we show that cavtratin inhibits CNV and the survival and migration of microglia and macrophages via JNK. Together, our data demonstrate the unique advantages of cavtratin in antiangiogenic therapy to treat neovascular diseases. PMID:28923916

Ophthalmic indications of amniotic membrane transplantation in Mexico: an eight years Amniotic Membrane Bank experience.

PubMed

Chávez-García, César; Jiménez-Corona, Aída; Graue-Hernández, Enrique O; Zaga-Clavellina, Verónica; García-Mejía, Mariana; Jiménez-Martínez, María Carmen; Garfias, Yonathan

2016-06-01

Amniotic membrane, the inner layer of the placenta, has biological properties (e.g. promotes epithelization, reduces fibrosis, secretes antimicrobial products and inhibits immune responses) which make it a useful option for several ophthalmologic procedures, especially those involving the ocular surface. Its use in eye surgery has been reported by other authors. To our knowledge, there is a lack of descriptive studies on surgical indications using amniotic membrane in Mexican population. Here we describe the eight years Amniotic Membrane Bank experience in Mexico, including a detailed protocol of the donors selection, tissue harvesting, preparation, storage and distribution of amniotic membrane since its establishment in 2007. Moreover, we describe the Ophthalmological indications of amniotic membrane transplantation of the total of 1686 amniotic membranes fragments used during eight years. The five most common indications for amniotic membrane transplantation were pterygium (46 %), corneal ulcers (12.6 %), conjunctival surface repair (11.1 %), neoplasms (7.4 %), and persistent epithelial defects (7.3 %). In addition, we compared the indications of amniotic membrane use in two different types of Institutions: general hospitals and ophthalmologic reference hospitals. We found interesting differences between the indications and use rates between these institutions, although pterygium was the most frequent pathology that amniotic membrane fragments were used in both institutions, there was up to a five-fold increase in the use of amniotic membrane for correction of persistent epithelial defects in reference hospitals which could be explained due to the more complex and severe ophthalmological pathologies admitted in reference hospitals. In conclusion, Amniotic Membrane is used in a numerous ocular pathologies and especially on pterygium in our Mexican population.

[Rapid imaging in orbito-ocular pathology. Contribution of gadolinium].

PubMed

Pigeau, I; Legeais, J M; D'Hermies, F; Fayet, B; Leport, M; Abenhaim, A; Guinet, C; Levy, C; Renard, G; Vadrot, D

1990-01-01

To evaluate Gradient-Echo Imaging (GEI) in orbito-ocular pathology, 15 volunteers and 34 patients (40 lesions) were examined with GEA T1 and GEA T2 (0.5 T). Results were compared with SE T1 in all cases, with SE T2 in 20 cases and with other imaging modalities (CT). 30 patients were examined before and after injection of gadolinium. Final diagnosis was obtained by surgery or biopsy in 24 cases or by combined results of imaging and clinical findings in 16 cases. Compared with SE, GEA demonstrated a better visualisation of optic nerve, orbital muscles, choroidal-retinal layer, lens capsule and episclera and a better detection of small lesions. It is very helpful for characterisation of lesions containing hemorrhages or paramagnetic components (melanine, gadolinium) or of vascular nature (angioma). Gadolinium was useful for detection of small lesions or characterisation of a few lesions. Thus GEA seems to be an efficient method for the evaluation of orbito-ocular pathology.

[Diagnostic significance of pathologic synkinesis for detection of pyramidal pathology].

PubMed

Baliasnyĭ, M M

1991-01-01

Five types of pathological synkinesis (++blepharo-ocular, ++blepharo-facial, ++bucco-manual, ++digito-digital on the hands, ++pedo-digital) are described. They are of definite importance for revealing pyramidal pathology including its early stages as well as for objective evaluation and observation of the time-course of changes in the illness.

Dry Eye Management: Targeting the Ocular Surface Microenvironment.

PubMed

Zhang, Xiaobo; M, Vimalin Jeyalatha; Qu, Yangluowa; He, Xin; Ou, Shangkun; Bu, Jinghua; Jia, Changkai; Wang, Junqi; Wu, Han; Liu, Zuguo; Li, Wei

2017-06-29

Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment.

Dry Eye Management: Targeting the Ocular Surface Microenvironment

PubMed Central

Zhang, Xiaobo; Jeyalatha M, Vimalin; Qu, Yangluowa; He, Xin; Ou, Shangkun; Bu, Jinghua; Jia, Changkai; Wang, Junqi; Wu, Han; Liu, Zuguo

2017-01-01

Dry eye can damage the ocular surface and result in mild corneal epithelial defect to blinding corneal pannus formation and squamous metaplasia. Significant progress in the treatment of dry eye has been made in the last two decades; progressing from lubricating and hydrating the ocular surface with artificial tear to stimulating tear secretion; anti-inflammation and immune regulation. With the increase in knowledge regarding the pathophysiology of dry eye, we propose in this review the concept of ocular surface microenvironment. Various components of the microenvironment contribute to the homeostasis of ocular surface. Compromise in one or more components can result in homeostasis disruption of ocular surface leading to dry eye disease. Complete evaluation of the microenvironment component changes in dry eye patients will not only lead to appropriate diagnosis, but also guide in timely and effective clinical management. Successful treatment of dry eye should be aimed to restore the homeostasis of the ocular surface microenvironment. PMID:28661456

A study of bedside ocular ultrasonography in the emergency department.

PubMed

Blaivas, Michael; Theodoro, Daniel; Sierzenski, Paul R

2002-08-01

The use of ocular ultrasonography for the evaluation of emergency patients has recently been described in the emergency medicine (EM) literature. There are a number of potential uses that may greatly aid the emergency physician (EP) and avoid lengthy consultation or other diagnostic tests. To examine the accuracy of bedside ultrasonography as performed by EPs for the evaluation of ocular pathology. This prospective, observational study took place in a high-volume, suburban community hospital with an EM residency program. All patients arriving with a history of eye trauma or acute change in vision were eligible to participate in the study. A 10-MHz linear-array transducer was used for imaging. All imaging was performed through a closed eyelid, using water-soluble ultrasound gel. Investigators filled out standardized data sheets and all examinations were taped for review. All ultrasound examinations were followed by orbital computed tomography or complete ophthalmologic evaluation from the ophthalmology service. Statistical analysis included sensitivity, specificity, and positive and negative predictive values. Sixty-one patients were enrolled in the study; 26 were found to have intraocular pathology on ultrasound. Of these, three had penetrating globe injuries, nine had retinal detachments, one had central retinal artery occlusion, and two had lens dislocations. The remaining pathology included vitreous hemorrhage and vitreous detachment. Emergency sonologists were in agreement with the criterion standard examination in 60 out of 61 cases. Emergency bedside ultrasound is highly accurate for ruling out and diagnosing ocular pathology in patients presenting to the emergency department. Further, it accurately differentiates between pathology that needs immediate ophthalmologic consultation and that which can be followed up on an outpatient basis.

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 Nerve Growth Factor (NGF) and NGF Eye Drop Application as Paradigms to Investigate NGF Neuroprotective and Reparative Actions.

PubMed

Tirassa, Paola; Rosso, Pamela; Iannitelli, Angela

2018-01-01

The eye is a central nervous system structure that is uniquely accessible to local treatment. Through the ocular surface, it is possible to access the retina, optic nerve, and brain. Animal models of retina degeneration or optic nerve crush could thus serve as tools to investigate whether and how factors, which are anterogradely or retrogradely transported through the optic nerve, might contribute to activate neuroprotection and eventually regeneration. Among these factors, nerve growth factor (NGF) plays a crucial role during development of the visual system, as well as during the entire life span, and in pathological conditions. The ability of NGF to exert survival and trophic actions on the retina and brain cells when applied intraocularly and topically as eye drops is critically reviewed here, together with the effects of ocular neurotrophins on neuronal pathways influencing body rhythm, cognitions, and behavioral functions. The latest data from animal models and humans are presented, and the mechanism of action of ocularly administered NGF is discussed. NGF eye drops are proposed as an experimental strategy to investigate the role and cellular targets of neurotrophins in the mechanism(s) underlying neurodegeneration/regeneration and their involvement in the regulation of neurological and behavioral dysfunctions.

Ultrasound biomicroscopic imaging in paediatric ocular toxocariasis.

PubMed

Liu, Jinghua; Li, Songfeng; Deng, Guangda; Yang, Wenli; Chen, Wei; Lu, Hai

2017-11-01

To determine the potential and usefulness of ultrasound biomicroscopy (UBM) as a diagnostic procedure on a larger cohort of paediatric patients with ocular toxocariasis. UBM was performed on 41 eyes of 41 patients with ocular toxocariasis in order to determine configuration of peripheral retina, pars plana and vitreous. Location and range of peripheral pathology using ophthalmoscopy with scleral indentation, UBM and intraoperative confirmation were recorded and compared. Pathological structures such as vitreous condensations or membranes of various configuration and extent were identified by UBM. UBM revealed peripheral granuloma and pseudocystic changes in the peripheral vitreous in 15 of 41 eyes. Compared with indirect ophthalmoscope, statistical analysis showed significant differences in the number of clock-hours of peripheral pathology detected by UBM (p=0.015), while statistical differences were not found between UBM and intraoperative peripheral examinations using scleral indentation (p=0.432). UBM seems to be a valuable and reliable diagnostic technique for the evaluation of patients with ocular toxocariasis. Longitudinal studies will have to determine the relevance of UBM findings for the individual clinical course and their influence on therapeutic decisions. 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/.

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.

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.

Significance of mucin on the ocular surface.

PubMed

Watanabe, Hitoshi

2002-03-01

To review the significance of mucin in the tear film and the ocular surface epithelium. Summary of the information on how mucin derived from the corneal and conjunctival epithelia and from goblet cells plays a role in the stability of the tear film over the ocular surface. The change in mucin expression derived from the ocular surface epithelium is also discussed with reference to ocular surface disease. The corneal and conjunctival epithelia produce transmembrane mucins such as MUC1, MUC2, and MUC4. In contrast, goblet cells produce the gel-forming secretory mucin, MUC5AC. The lacrimal gland produces MUC7. On the ocular surface, cooperation between transmembrane mucin and secretory mucin is necessary for the stability of the tear film. The expression of mucin from the ocular surface epithelium is coordinated from the time of eyelid opening and is altered in conditions such as squamous metaplasia and dry eye. This alteration may result in instability of the tear film. CONCLU SION: The induction of mucin from the ocular surface may facilitate the stability of the tear film, and increased knowledge may lead to the development of a new modality for the treatment of dry eye.

Ocular and uteroplacental pathology in a macaque pregnancy with congenital Zika virus infection

PubMed Central

Stewart, Laurel M.; Koenig, Michelle; Semler, Matthew; Breitbach, Meghan E.; Zeng, Xiankun; Weiler, Andrea M.; Barry, Gabrielle L.; Thoong, Troy H.; Wiepz, Gregory J.; Dudley, Dawn M.; Simmons, Heather A.; Mejia, Andres; Morgan, Terry K.; Salamat, M. Shahriar; Kohn, Sarah; Antony, Kathleen M.; Mohns, Mariel S.; Hayes, Jennifer M.; Schultz-Darken, Nancy; Schotzko, Michele L.; Peterson, Eric; Capuano, Saverio; Osorio, Jorge E.; O’Connor, Shelby L.; O’Connor, David H.; Golos, Thaddeus G.

2018-01-01

Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM), intraamniotic bacterial infection and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout fetal tissues and maternal immune system tissues at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal uterus, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in a rhesus macaque. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital ZIKV infection previously. While this case of ZIKV infection during pregnancy was complicated by bacterial infection with PPROM, the role of ZIKV on this outcome cannot be precisely defined, and further nonhuman primate studies will determine if increased risk for PPROM or other adverse pregnancy outcomes are associated with congenital ZIKV infection. PMID:29381706

Dry eye symptoms are increased in mice deficient in phospholipid transfer protein (PLTP).

PubMed

Setälä, Niko L; Metso, Jari; Jauhiainen, Matti; Sajantila, Antti; Holopainen, Juha M

2011-05-01

In the tear fluid the outermost part facing the tear-air interface is composed of lipids preventing evaporation of the tears. Phospholipid transfer protein (PLTP) mediates phospholipid transfer processes between serum lipoproteins and is also a normal component of human tears. To study whether PLTP plays any functional role in tear fluid we investigated PLTP-deficient mice, applying functional and morphologic analyses under normal housing and experimentally induced dry eye conditions. Aqueous tear fluid production, corneal epithelial morphology, barrier function, and occludin expression were assessed. In mice with a full deficiency of functional PLTP enhanced corneal epithelial damage, increased corneal permeability to carboxyfluorescein, and decreased corneal epithelial occludin expression were shown. These pathologic signs were worsened by experimentally induced dry eye both in wild-type and PLTP knock-out mice. Deficiency in the production of tear PLTP in mice is accompanied by corneal epithelial damage, a feature that is typical in human dry eye syndrome (DES). To complement animal experiments we collected tear fluid from human dry eye patients as well as healthy control subjects. Increased tear fluid PLTP activity was observed among DES patients. In conclusion, the presence of PLTP in tear fluid appears to be essential for maintaining a healthy and functional ocular surface. Increased PLTP activity in human tear fluid in DES patients suggests an ocular surface protective role for this lipid transfer protein. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A case report of ocular toxocariasis.

PubMed

Azira, N M S; Zeehaida, M

2011-04-01

Ocular toxocariasis is prevalent among children. The symptoms and signs may mimic other ocular pathologies such as malignancies and other infectious diseases (such as toxoplasmosis and syphilis). We presented a case of progressive blurring of vision in a single eye of a 9-year-old boy. The presence of anti-toxocara antibody in serum samples helps to confirmation the diagnosis in our patient. Despite of treatment, the boy had lost his vision on the affected eye.

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.

Conjunctival Goblet Cell Function: Effect of Contact Lens Wear and Cytokines

PubMed Central

García-Posadas, Laura; Contreras-Ruiz, Laura; Soriano-Romaní, Laura; Dartt, Darlene A.; Diebold, Yolanda

2015-01-01

This review focuses on conjunctival goblet cells and their essential function in the maintenance of eye health. The main function of goblet cells is to produce and secrete mucins that lubricate the ocular surface. An excess or a defect in those mucins leads to several alterations that makes goblet cells central players in maintaining the proper mucin balance and ensuring the correct function of ocular surface tissues. A typical pathology that occurs with mucous deficiency is dry eye disease, whereas the classical example of mucous hyperproduction is allergic conjunctivitis. In this review we analyze how goblet cell number and function can be altered in these diseases and in contact lens wearers. We found that most published studies focused exclusively on goblet cell number. However, recent advances have demonstrated that, along with mucin secretion, goblet cells are also able to secrete cytokines and respond to them. We describe the effect of different cytokines on goblet cell proliferation and secretion. We conclude that it is important to further explore the effect of contact lens wear and cytokines on conjunctival goblet cell function. PMID:26067396

A challenging case of ocular melanoma.

PubMed

Costache, Mariana; Dumitru, Adrian Vasile; Pătraşcu, Oana Maria; Popa-Cherecheanu, Daniela Alina; Bădilă, Patricia; Miu, Jeni Cătălina; Procop, Alexandru; Popa, Manuela; Tampa, Mircea Ştefan; Sajin, Maria; Simionescu, Olga; Cîrstoiu, Monica Mihaela

2015-01-01

Ocular melanoma is a rare malignancy found in clinical practice. In this paper, we present a case of highly aggressive ocular melanoma, which was surgically removed at the Department of Ophthalmology and diagnosed at the Department of Pathology, Emergency University Hospital, Bucharest, Romania, using conventional histopathological techniques. Uveal melanoma, a subset of ocular melanoma, has a distinct behavior in comparison to cutaneous melanoma and has a widely divergent prognosis. Approximately half of patients with ocular melanoma will develop metastatic disease, predominantly with hepatic, pulmonary or cerebral location, over a 10 to 15 years period. No systemic therapy was associated with an evident clinical outcome for patients with advanced disease and overall survival rate remains poor.

Healthy and pathological cerebellar Spiking Neural Networks in Vestibulo-Ocular Reflex.

PubMed

Antonietti, Alberto; Casellato, Claudia; Geminiani, Alice; D'Angelo, Egidio; Pedrocchi, Alessandra

2015-01-01

Since the Marr-Albus model, computational neuroscientists have been developing a variety of models of the cerebellum, with different approaches and features. In this work, we developed and tested realistic artificial Spiking Neural Networks inspired to this brain region. We tested in computational simulations of the Vestibulo-Ocular Reflex protocol three different models: a network equipped with a single plasticity site, at the cortical level; a network equipped with a distributed plasticity, at both cortical and nuclear levels; a network with a pathological plasticity mechanism at the cortical level. We analyzed the learning performance of the three different models, highlighting the behavioral differences among them. We proved that the model with a distributed plasticity produces a faster and more accurate cerebellar response, especially during a second session of acquisition, compared with the single plasticity model. Furthermore, the pathological model shows an impaired learning capability in Vestibulo-Ocular Reflex acquisition, as found in neurophysiological studies. The effect of the different plasticity conditions, which change fast and slow dynamics, memory consolidation and, in general, learning capabilities of the cerebellar network, explains differences in the behavioral outcome.

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.

A case report of ocular toxocariasis

PubMed Central

Azira, NMS; Zeehaida, M

2011-01-01

Ocular toxocariasis is prevalent among children. The symptoms and signs may mimic other ocular pathologies such as malignancies and other infectious diseases (such as toxoplasmosis and syphilis). We presented a case of progressive blurring of vision in a single eye of a 9-year-old boy. The presence of anti-toxocara antibody in serum samples helps to confirmation the diagnosis in our patient. Despite of treatment, the boy had lost his vision on the affected eye. PMID:23569750

Efficacy of High Frequency Ultrasound in Localization and Characterization of Orbital Lesions

PubMed Central

Gurushankar, G; Bhimarao; Kadakola, Bindushree

2015-01-01

Background The complicated anatomy of orbit and the wide spectrum of pathological conditions present a formidable challenge for early diagnosis, which is critical for management. Ultrasonography provides a detailed cross sectional anatomy of the entire globe with excellent topographic visualization and real time display of the moving organ. Objectives of the study To evaluate the efficacy of high frequency Ultrasound in localization of orbital diseases and to characterize various orbital pathologies sonologically. Materials and Methods Hundred eyes of 85 patients were examined with ultrasound using linear high frequency probe (5 to 17 MHz) of PHILPS IU22 ultrasound system. Sonological diagnosis was made based on location, acoustic characteristics, kinetic properties and Doppler flow dynamics. Final diagnosis was made based on clinical & laboratory findings/higher cross-sectional imaging/surgery & histopathology (as applicable). Diagnostic accuracy of ultrasonography was evaluated and compared with final diagnosis. Results The distinction between ocular and extraocular pathologies was made in 100% of cases. The overall sensitivity, specificity, NPV and accuracy of ultrasonography were 94.2%, 98.8%, 92.2% & 94.9% respectively for diagnosis of ocular pathologies and 94.2%, 99.2%, 95.9% & 95.2% respectively for extra ocular pathologies. Conclusion Ultrasonography is a readily available, simple, cost effective, non ionizing and non invasive modality with overall high diagnostic accuracy in localising and characterising orbital pathologies. It has higher spatial and temporal resolution compared to CT/MRI. However, CT/MRI may be indicated in certain cases for the evaluation of calcifications, bony involvement, extension to adjacent structures and intracranial extension. PMID:26500977

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.

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.

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.

Functional vision loss: a diagnosis of exclusion.

PubMed

Villegas, Rex B; Ilsen, Pauline F

2007-10-01

Most cases of visual acuity or visual field loss can be attributed to ocular pathology or ocular manifestations of systemic pathology. They can also occasionally be attributed to nonpathologic processes or malingering. Functional vision loss is any decrease in vision the origin of which cannot be attributed to a pathologic or structural abnormality. Two cases of functional vision loss are described. In the first, a 58-year-old man presented for a baseline eye examination for enrollment in a vision rehabilitation program. He reported bilateral blindness since a motor vehicle accident with head trauma 4 years prior. Entering visual acuity was "no light perception" in each eye. Ocular health examination was normal and the patient made frequent eye contact with the examiners. He was referred for neuroimaging and electrophysiologic testing. The second case was a 49-year-old man who presented with a long history of intermittent monocular diplopia. His medical history was significant for psycho-medical evaluations and a diagnosis of factitious disorder. Entering uncorrected visual acuities were 20/20 in each eye, but visual field testing found constriction. No abnormalities were found that could account for the monocular diplopia or visual field deficit. A diagnosis of functional vision loss secondary to factitious disorder was made. Functional vision loss is a diagnosis of exclusion. In the event of reduced vision in the context of a normal ocular health examination, all other pathology must be ruled out before making the diagnosis of functional vision loss. Evaluation must include auxiliary ophthalmologic testing, neuroimaging of the visual pathway, review of the medical history and lifestyle, and psychiatric evaluation. Comanagement with a psychiatrist is essential for patients with functional vision loss.

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.

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.

Laser applications and system considerations in ocular imaging

PubMed Central

Elsner, Ann E.; Muller, Matthew S.

2009-01-01

We review laser applications for primarily in vivo ocular imaging techniques, describing their constraints based on biological tissue properties, safety, and the performance of the imaging system. We discuss the need for cost effective sources with practical wavelength tuning capabilities for spectral studies. Techniques to probe the pathological changes of layers beneath the highly scattering retina and diagnose the onset of various eye diseases are described. The recent development of several optical coherence tomography based systems for functional ocular imaging is reviewed, as well as linear and nonlinear ocular imaging techniques performed with ultrafast lasers, emphasizing recent source developments and methods to enhance imaging contrast. PMID:21052482

[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.

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.

Oxidative stress and its downstream signaling in aging eyes

PubMed Central

Pinazo-Durán, María Dolores; Gallego-Pinazo, Roberto; García-Medina, Jose Javier; Zanón-Moreno, Vicente; Nucci, Carlo; Dolz-Marco, Rosa; Martínez-Castillo, Sebastián; Galbis-Estrada, Carmen; Marco-Ramírez, Carla; López-Gálvez, Maria Isabel; Galarreta, David J; Díaz-Llópis, Manuel

2014-01-01

Background Oxidative stress (OS) and its biomarkers are the biochemical end point of the imbalance between reactive oxygen species (ROS) production and the ability of the antioxidant (AOX) biological systems to fight against oxidative injury. Objective We reviewed the role of OS and its downstream signaling in aging eyes. Methods A search of the literature and current knowledge on the physiological and pathological mechanisms of OS were revisited in relation to the eyes and the aging process. Most prevalent ocular diseases have been analyzed herein in relation to OS and nutraceutic supplements, such as dry-eye disorders, glaucoma, age-related macular degeneration, and diabetic retinopathy. Results Clinical, biochemical, and molecular data from anterior and posterior eye segment diseases point to OS as the common pathogenic mechanism in the majority of these ocular disorders, many of which are pathologies causing visual impairment, blindness, and subsequent loss of life quality. Studies with nutraceutic supplements in aging eye-related pathologies have also been reviewed. Conclusion OS, nutritional status, and nutraceutic supplements have to be considered within the standards of care of older ophthalmologic patients. OS biomarkers and surrogate end points may help in managing the aging population with ocular diseases. PMID:24748782

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

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.

Confocal microscopy of epithelial and langerhans cells of the cornea in patients using travoprost drops containing two different preservatives.

PubMed

Marsovszky, László; Resch, Miklós D; Visontai, Zsuzsanna; Németh, János

2014-07-01

The recently developed confocal cornea microscopy offers the opportunity to examine pathologies of the cornea and to gain insight into the activity of innate immunity. We aimed to investigate the corneal epithelial and Langerhans cell (LC) densities along with dry eye parameters in primary open-angle glaucoma (POAG) subjects, treated with either of two commercially available travoprost 0.004 % topical medications containing different preservatives. (1: benzalkonium chloride 0.015 % (TravBAK) and 2: polyquaternium-1 (PQ) 0.001 % (TravPQ). Consecutive case series of nineteen POAG patients on TravBAK (mean age: 64.8 ± 13.6 years), nineteen POAG patients on TravPQ (mean age: 66.8 ± 11.3 years) and nineteen age-matched healthy control subjects (63.8 ± 8.2 years). Ocular surface disease index (OSDI), lid parallel conjunctival folds (LIPCOF), Schirmer test (ST) and tear break up time (TBUT) were assessed, and then corneal epithelial and LC densities were investigated with confocal microscopy. Tear production was significantly reduced in both glaucoma patient groups compared to healthy individuals (p < 0.05). TBUT was significantly reduced and epithelial cell densities were significantly greater in patients treated with TravBAK compared to healthy individuals (p < 0.05 for all). LC densities were greater in both glaucoma groups compared to control subjects (p < 0.05 for all). Travoprost therapy may compromise ocular surface. The limited alertness of the corneal immune system found in patients with TravPQ can be considered as indicators of a less disturbed ocular surface and better controlled corneal homeostasis.

Ocular toxicity of fludarabine

PubMed Central

Ding, Xiaoyan; Herzlich, Alexandra A; Bishop, Rachel; Tuo, Jingsheng; Chan, Chi-Chao

2008-01-01

The purine analogs, fludarabine and cladribine represent an important class of chemotherapy agents used to treat a broad spectrum of lymphoid malignancies. Their toxicity profiles include dose-limiting myelosuppression, immunosuppression, opportunistic infection and severe neurotoxicity. This review summarizes the neurotoxicity of high- and standard-dose fludarabine, focusing on the clinical and pathological manifestations in the eye. The mechanisms of ocular toxicity are probably multifactorial. With increasing clinical use, an awareness of the neurological and ocular vulnerability, particularly to fludarabine, is important owing to the potential for life- and sight-threatening consequences. PMID:18461151

Occupational peri-ocular contact dermatitis due to sensitization against black rubber components of a microscope.

PubMed

Kuijpers, D I M; Hillen, F; Frank, J A

2006-08-01

A 24-year-old female working in the Department of Pathology of a University Hospital developed an acute peri-ocular eczema clearly being related to her daily work at the microscope. Patch testing revealed delayed type hypersensitivity against the black rubber mix, N-isopropyl-N'-phenyl paraphenylenediamine, N-cyclohexyl-N'-phenyl paraphenylenediamine and the rubber ring situated on the ocular of the respective microscope. This is the first report, to our knowledge, on peri-orbital allergic contact eczema because of sensitization with rubber components of a microscope.

Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

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

Zhang, Han; Sonoda, Koh-Hei, E-mail: sonodak@med.kyushu-u.ac.jp; Hijioka, Kuniaki

2009-04-17

Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8{sup +} T cells reduced pathological preretinal NV,more » with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8{sup +} T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.« less

Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization.

PubMed

Zhang, Han; Sonoda, Koh-Hei; Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro

2009-04-17

Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8+ T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8+ T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

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.

Multiple etiologies of equine recurrent uveitis--A natural model for human autoimmune uveitis: A brief review.

PubMed

Witkowski, Lucjan; Cywinska, Anna; Paschalis-Trela, Katarzyna; Crisman, Mark; Kita, Jerzy

2016-02-01

Equine recurrent uveitis (ERU) has various etiologies, with Leptospira infection and genetic predisposition being the leading risk factors. Regardless of etiology, expression of ocular proteins associated with maintenance of the blood-ocular barrier is impaired in ERU. The recurring-remitting cycle of ERU repeatedly disrupts the blood-ocular barrier, allowing the previously immune-privileged ocular environment to become the site of a progressive local autoimmune pathology that ultimately results in tissue destruction and vision loss. The immune-mediated process involves humoral and cellular mechanisms. Intraocular antibodies either produced in the eye or that leak through the blood-ocular barrier, are often present at higher levels than in serum and react with antigens in ocular tissue of horses with ERU. Ocular infiltration of auto-aggressive lymphocytes occurs with each uveitis episode and is the most crucial contributor to inflammation and eye damage. Recurring uveitis episodes may be initiated when epitopes of an ocular antigen become visible to the immune system (intramolecular spreading) or another autoantigen (intermolecular spreading), resulting in a new inflammatory reaction. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

[Challenge and treatment strategy for ocular surface damage in patients with long term use of antiglaucoma drugs].

PubMed

He, Xiang-Ge

2011-02-01

Long term use of topical anti-glaucoma drugs has been shown to induce chronic conjunctivitis, superficial punctate keratitis (SPK) and dry eye symptom. Under these conditions, a loss of goblet cells in conjunctiva, epithelial squamous metaplasia and apoptosis were morphologically revealed. Benzalkonium Chloride (BKC), a most frequently used preservative in eye drops, has been found to be an important factor causing ocular surface damage. Furthermore, a big challenge for ophthalmologists is that toxic damage of medication to ocular surface tissues is mild, poor specificity, and delayed manifestation in patients, especially when coexisting with other ocular surface diseases. Impairment of ocular surface tissues greatly impacts the life quality of patients and subsequently influences compliance with glaucoma therapy. This paper emphasizes to take measures to prevent ocular surface tissue damage resulted from chronic use of topical anti-glaucoma drugs and further discusses the treatment strategy. Effective and long-lasting action drugs should always be selected for glaucomatous patients in order to decrease the frequency of topical instillation or at a more expensive medication, a fixed combination formula can be considered for glaucoma therapy. An early surgery or laser treatment is also proposed for the patients who require an IOP reduction with an existing ocular surface impairment. Future investigation and development of new medications with long-term efficacy and appropriate BKC are suggested and preservative-free or drugs with new preservative materials recommended.

Conjunctival flora of healthy and diseased eyes of grey seals (Halichoerus grypus): implications for treatment.

PubMed

Fleming, M; Bexton, S

2016-07-23

Ocular pathology is relatively common in stranded seals admitted to wildlife rehabilitation hospitals. Some have pre-existing problems, while others develop eye problems in captivity, and in particular ulcerative keratitis, due to factors such as large prominent eyes, suboptimal water quality, trauma and infighting. Despite treatment, corneal ulcerations can rapidly progress to 'melting' ulcers with subsequent rupture of the globe. In this case series, 32 grey seals (Halichoerus grypus) had conjunctival swabs taken on admission to a UK wildlife hospital to identify ocular bacterial flora and nine had subsequent swabs taken after four weeks to see if this changed in captivity. Additionally, nine seals with ocular pathology were also swabbed. Although a wide range of bacteria were cultured on admission, the most common isolates were Gemella haemolysans, Escherichia coli and Clostridium perfringens All 'melting' ulcers were associated with Pseudomonas aeruginosa, which suggests this bacterial species may be significant in the pathogenesis of progressive stromal ulceration in grey seals. British Veterinary Association.

Apatinib, an Inhibitor of Vascular Endothelial Growth Factor Receptor 2, Suppresses Pathologic Ocular Neovascularization in Mice.

PubMed

Kim, Koung Li; Suh, Wonhee

2017-07-01

Vascular endothelial growth factor (VEGF) signaling via VEGF receptor 2 (VEGFR2) plays a crucial role in pathologic ocular neovascularization. In this study, we investigated the antiangiogenic effect of apatinib, a pharmacologic inhibitor of VEGFR2 tyrosine kinase, against oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) in mice. Western blotting and in vitro angiogenesis assays were performed using human retinal microvascular endothelial cells (HRMECs). OIR was induced in neonatal mice by exposure to 75% oxygen from postnatal day (P) 7 to P12 and to room air from P12 to P17. Experimental CNV was induced in mice using laser photocoagulation. Apatinib was intravitreally and orally administered to mice. Neovascularization and phosphorylation of VEGFR2 were evaluated by immunofluorescence staining. Apatinib inhibited VEGF-mediated activation of VEGFR2 signaling and substantially reduced VEGF-induced proliferation, migration, and cord formation in HRMECs. A single intravitreal injection of apatinib significantly attenuated retinal or choroidal neovascularization in mice with OIR or laser injury-induced CNV, respectively. Retinal or choroidal tissues of the eyes treated with apatinib exhibited substantially lower phosphorylation of VEGFR2 than those of controls injected with vehicle. Intravitreal injection of apatinib did not cause noticeable ocular toxicity. Moreover, oral administration of apatinib significantly reduced laser-induced CNV in mice. Our study demonstrates that apatinib inhibits pathologic ocular neovascularization in mice with OIR or laser-induced CNV. Apatinib may, therefore, be a promising drug for the prevention and treatment of ischemia-induced proliferative retinopathy and neovascular age-related macular degeneration.

Human host defense peptides - role in maintaining human homeostasis and pathological processes.

PubMed

Dawgul, Malgorzata Anna; Greber, Katarzyna Ewa; Sawicki, Wieslaw; Kamysz, Wojciech

2016-12-12

The human body expresses over 100 host defense peptides and proteins (antimicrobial peptides, AMPs). The compounds are produced by tissues and mucosal surfaces, e.g. skin, the digestive and urinary tract, the ocular surface and neutrophils, and are believed to play a crucial role in defense from microbial infection. They are considered to protect the human body against microbial infections due to their antimicrobial and immunomodulatory activities. As well as having strong antimicrobial activity towards a broad spectrum of microorganisms, AMPs have been found to interact with neutrophils, monocytes and T-cells and promote the production of cytokines. They also neutralize the action of lipopolysaccharide (LPS) and play a crucial role in wound healing processes. In response to the microbial stimuli the AMPs are released in order to fight the infection, however there are several microorganisms evading the human immune system by downregulation of AMPs. Decreased or elevated expression of AMPs is associated also with several non-infectious diseases. Despite numerous studies conducted in the field of AMPs over the last few decades, their exact role in physiological and pathological processes remains to be explained. In this paper, we review the most significant human AMPs and their potential roles in maintaining human homeostasis as well as in pathological processes.

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.

Ocular findings in a case of trisomy 18 with variant of Dandy-Walker syndrome.

PubMed

Lim, Fong-Fong; Ng, Yan-Yan; Hu, Jui-Ming; Chen, Suh-Jen; Su, Pen-Hua; Chen, Jia-Yuh

2010-10-01

Trisomy 18 is the second most common chromosomal syndrome and has multiple dysmorphic features. However, ocular findings in trisomy 18 are rarely reported. Retinal folds are the most common ocular finding described to date, although retinal hypopigmentation, dysplasia, and areas of hemorrhage and gliosis are also found in trisomy 18. Dandy-Walker syndrome is a brain malformation that has been reported in association with numerous chromosomal abnormalities, although it has rarely been reported in association with trisomy 18. Here, we present a case of trisomy 18 with ocular pathology and variant of Dandy-Walker syndrome, a combination that has not previously been reported. Copyright © 2010 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.

Animal models to assess the therapeutic efficacy of human serum and serum-converted platelet lysates for dry eye syndrome: Seeing is believing.

PubMed

Tseng, Ching-Li; Seghatchian, Jerard; Burnouf, Thierry

2015-08-01

There is much interest in the clinical use of serum-converted human blood or platelet concentrates in regenerative medicine, most specifically for wound healing and tissue repair of soft and hard tissues. The scientific rationale supporting the clinical efficacy of these preparations is based on the expectation that their physiological mixture of natural growth factors can orchestrate cell expansion and differentiation in vivo. However, a lack of standardization and regulatory oversight of these blood materials maintain a perception of uncertainty in the scientific and medical community on the value of these preparations for some clinical indications. More studies are needed to understand the mechanism of action underlying their expected efficacy and standardize their use, and benefit from their biological versatility. One application of serum is as eye drop for treating dry eye syndrome (DES), a multifactorial disease of the ocular surface, which has a prevalence of 15% of more in the population. DES can lead to chronic inflammation of the ocular surface, surface impairment in the cornea and conjunctiva, and, in patients with Sjogren syndrome, result in a disruption of the ocular surface epithelium. Objective experimental assessment of safety and efficacy of serum eye drops can help establish scientific rationale in optimal product composition and use. This can be achieved, first, through cell cultures with relevant cell models, before considering, then, animal studies using DES animal models. Several models have been evaluated and are reported in this concise review. The model we have developed encompasses the use of rabbits, where their eyes are treated with 0.1% benzalkonium chloride (BAC), a common preservative in ophthalmic agents, 3 times daily for 4 weeks. This relatively mild treatment results in moderate DES pathology, with a stable shortage of tear secretion throughout a 7-week study period, which we found suitable for assessing efficacy of serum eye drops. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

APR-246/PRIMA-1Met Inhibits and Reverses Squamous Metaplasia in Human Conjunctival Epithelium.

PubMed

Li, Jing; Li, Cheng; Wang, Guoliang; Liu, Zhen; Chen, Pei; Yang, Qichen; Dong, Nuo; Wu, Huping; Liu, Zuguo; Li, Wei

2016-02-01

Squamous metaplasia is a common pathologic condition in ocular surface diseases for which there is no therapeutic medication in clinic. In this study, we investigated the effect of a small molecule, APR-246/PRIMA-1(Met), on squamous metaplasia in human conjunctival epithelium. Human conjunctival explants were cultured for up to 12 days under airlifting conditions. Epithelial cell differentiation and proliferation were assessed by Cytokeratin 10 (K10), K14, K19, Pax6, MUC5AC, and p63 immunostaining patterns. β-catenin and TCF-4 immunofluorescent staining and real-time PCR characterized Wnt signaling pathway involvement. Pterygium clinical samples were cultured under airlifting conditions with or without APR-246 for 4 days. p63, K10, β-catenin, and TCF-4 expression in pterygial epithelium was determined by immunofluorescent staining and real-time PCR. Airlift conjunctival explants resulted in increased stratification and intrastromal epithelial invagination. Such pathology was accompanied by increases in K10, K14, and p63 expression, whereas K19 and Pax6 levels declined when compared to those in freshly isolated tissue. On the other hand, APR-246 reversed all of these declines in K10, K14, and p63 expression. Furthermore, K19 and Pax6 increased along with rises in goblet cell density. These effects of APR-246 were accompanied by near restoration of normal conjunctival epithelial histology. APR-246 also reversed squamous metaplasia in pterygial epithelium that had developed after 4 days in ex vivo culture. Reductions in squamous metaplasia induced by APR-246 suggest it may provide a novel therapeutic approach in different squamous metaplasia-associated ocular surface diseases.

Bell's Palsy Treatment

MedlinePlus

Subspecialties Cataract/Anterior Segment Comprehensive Ophthalmology Cornea/External Disease Glaucoma Neuro-Ophthalmology/Orbit Pediatric Ophthalmology/Strabismus Ocular Pathology/Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis ...

Using Eye Makeup

MedlinePlus

Subspecialties Cataract/Anterior Segment Comprehensive Ophthalmology Cornea/External Disease Glaucoma Neuro-Ophthalmology/Orbit Pediatric Ophthalmology/Strabismus Ocular Pathology/Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis ...

Reduced vision in highly myopic eyes without ocular pathology: the ZOC-BHVI high myopia study.

PubMed

Jong, Monica; Sankaridurg, Padmaja; Li, Wayne; Resnikoff, Serge; Naidoo, Kovin; He, Mingguang

2018-01-01

The aim was to investigate the relationship of the magnitude of myopia with visual acuity in highly myopic eyes without ocular pathology. Twelve hundred and ninety-two highly myopic eyes (up to -6.00 DS both eyes, no astigmatic cut-off) with no ocular pathology from the ZOC-BHVI high myopia study in China, had cycloplegic refraction, followed by subjective refraction and visual acuities and axial length measurement. Two logistic regression models were undertaken to test the association of age, gender, refractive error, axial length and parental myopia with reduced vision. Mean group age was 19.0 ± 8.6 years; subjective spherical equivalent refractive error was -9.03 ± 2.73 D; objective spherical equivalent refractive error was -8.90 ± 2.60 D and axial length was 27.0 ± 1.3 mm. Using visual acuity, 82.4 per cent had normal vision, 16.0 per cent had mildly reduced vision, 1.2 per cent had moderately reduced vision, 0.3 per cent had severely reduced vision and no subjects were blind. The percentage with reduced vision increased with spherical equivalent to 74.5 per cent from -15.00 to -39.99 D, axial length to 67.7 per cent of eyes from 30.01 to 32.00 mm and age to 22.9 per cent of those 41 years and over. Spherical equivalent and axial length were significantly associated with reduced vision (p < 0.0001). Age and parental myopia were not significantly associated with reduced vision. Gender was significant for one model (p = 0.04). Mildly reduced vision is common in high myopia without ocular pathology and is strongly correlated with greater magnitudes of refractive error and axial length. Better understanding is required to minimise reduced vision in high myopes. © 2017 Optometry Australia.

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.

Anterior ocular abnormalities of captive Asian elephants (Elephas maximus indicus) in Thailand.

PubMed

Kraiwong, Natapong; Sanyathitiseree, Pornchai; Boonprasert, Khajohnpat; Diskul, Phiphatanachatr; Charoenphan, Patara; Pintawong, Weerasak; Thayananuphat, Aree

2016-07-01

To survey and classify anterior ocular abnormalities in 1478 captive Asian elephants (Elephas maximus indicus) in six regions of Thailand. Anterior ocular examination was performed in both eyes (n = 2956) of 1478 elephants selected from the annual health check program involving 2958 animals within six regions of Thailand from January to November 2013. Lesions were described and compared between age and gender. A total of 17.83% (527/2956) of examined eyes from 24.97% (369/1478) of examined elephants had anterior ocular abnormalities. The most common lesions in these examined eyes were frothy ocular discharge (5.85%), corneal edema (5.31%), and conjunctivitis (5.18%). In addition, epiphora, phthisis bulbi, other corneal abnormalities, anterior uveitis, and lens abnormalities were noted. Almost all lesions increased in frequency with age (P < 0.01). Regular ophthalmic examination in elephants should be included in their annual health check program. Early detection and treatment of any ocular abnormality may avoid the development of subsequent irreversible ocular pathology. © 2015 American College of Veterinary Ophthalmologists.

What Is Refractive Surgery?

MedlinePlus

Subspecialties Cataract/Anterior Segment Comprehensive Ophthalmology Cornea/External Disease Glaucoma Neuro-Ophthalmology/Orbit Pediatric Ophthalmology/Strabismus Ocular Pathology/Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis ...

Ocular flutter following Zika virus infection.

PubMed

Karam, Emely; Giraldo, Jose; Rodriguez, Flor; Hernandez-Pereira, Carlos E; Rodriguez-Morales, Alfonso J; Blohm, Gabriela M; Paniz-Mondolfi, Alberto E

2017-12-01

Zika virus (ZIKV) is an emerging flavivirus which has been linked to a number of neurologic manifestations such as Guillain-Barré syndrome (GBS), transverse myelitis, and meningo-encephalitis. Ophthalmologic manifestations are increasingly being reported; however, ocular dyskinesias have not been described in this context to date. Herein, we report a case of a 22-year-old female who presented with ocular flutter and associated Guillain-Barré syndrome following acute ZIKV infection. We speculate that although such symptoms may have originated from a direct viral insult, a post-infectious autoimmune mechanism may not be excluded. Physicians should include ZIKV as well as other flaviviruses in their diagnostic workup for all patients with ocular flutter/opsoclonus, after excluding other non-infectious causes of central nervous system pathology. To the best of our knowledge, this is the first report on the association of ocular flutter, GBS, and ZIKV infection.

Nanotherapies for the treatment of ocular diseases.

PubMed

Reimondez-Troitiño, S; Csaba, N; Alonso, M J; de la Fuente, M

2015-09-01

The topical route is the most frequent and preferred way to deliver drugs to the eye. Unfortunately, the very low ocular drug bioavailability (less than 5%) associated with this modality of administration, makes the efficient treatment of several ocular diseases a significant challenge. In the last decades, it has been shown that specific nanocarriers can interact with the ocular mucosa, thereby increasing the retention time of the associated drug onto the eye, as well as its permeability across the corneal and conjunctival epithelium. In this review, we comparatively analyze the mechanism of action and specific potential of the most studied nano-drug delivery carriers. In addition, we present the success achieved until now using a number of nanotherapies for the treatment of the most prevalent ocular pathologies, such as infections, inflammation, dry eye, glaucoma, and retinopathies. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

[Acquired disorders of color vision].

PubMed

Lascu, Lidia; Balaş, Mihaela

2002-01-01

This article is a general view of acquired disorders of color vision. The revision of the best known methods and of the etiopathogenic classification is not very important in ophthalmology but on the other hand, the detection of the blue defect advertise and associated ocular pathology. There is a major interest in serious diseases as multiple sclerosis, AIDS, diabetes melitus, when the first ocular sign can be a defect in the color vision.

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.

Childhood Eye Diseases and Conditions

MedlinePlus

Subspecialties Cataract/Anterior Segment Comprehensive Ophthalmology Cornea/External Disease Glaucoma Neuro-Ophthalmology/Orbit Pediatric Ophthalmology/Strabismus Ocular Pathology/Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis ...

Genetic Testing and Eye Disease

MedlinePlus

Subspecialties Cataract/Anterior Segment Comprehensive Ophthalmology Cornea/External Disease Glaucoma Neuro-Ophthalmology/Orbit Pediatric Ophthalmology/Strabismus Ocular Pathology/Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis ...

What Is Giant Cell Arteritis?

MedlinePlus

Subspecialties Cataract/Anterior Segment Comprehensive Ophthalmology Cornea/External Disease Glaucoma Neuro-Ophthalmology/Orbit Pediatric Ophthalmology/Strabismus Ocular Pathology/Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis ...

Corneal erosion and Kindler syndrome.

PubMed

Signes-Soler, Isabel; Rodriguez-Prats, Jose Luis; Carbonell, Stella; Tañá-Rivero, Pedro

2013-01-01

To describe a very common corneal pathology in a patient with Kindler syndrome. We report the case of a 21-year-old woman, who presented to the Ophthalmology Department as an emergency presentation because of ocular pain in the left eye that radiated to other areas of the face and neck. After an exhaustive clinical interview, it was determined that the patient had a rare disease (Kindler syndrome). Ophthalmologic examination revealed corneal erosion on the left eye. No other significant conditions were found. After the application of conventional treatment, the corneal integrity was completely restored. We describe a very rare syndrome. Although conventional treatment restored corneal integrity, it is important to remember that ocular signs and symptoms are often associated with systemic pathologies.

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.

Ocular Manifestations of Mosquito-Transmitted Diseases.

PubMed

Karesh, James W; Mazzoli, Robert A; Heintz, Shannon K

2018-03-01

Of the 3,548 known mosquito species, about 100 transmit human diseases. Mosquitoes are distributed globally throughout tropical and temperate regions where standing water sources are available for egg laying and the maturation of larva. Female mosquitoes require blood meals for egg production. This is the main pathway for disease transmission. Mosquitoes carry several pathogenic organisms responsible for significant ocular pathology and vision loss including West Nile, Rift Valley, chikungunya, dengue viruses, various encephalitis viruses, malarial parasites, Francisella tularensis, microfilarial parasites, including Dirofilaria, Wuchereria, and Brugia spp., and human botfly larvae. Health care providers may not be familiar with many of these mosquito-transmitted diseases or their associated ocular findings delaying diagnosis, treatment, and recovery of visual function. This article aims to provide an overview of the ocular manifestations associated with mosquito-transmitted diseases.

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

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.

Biophotonics in diagnosis and modeling of tissue pathologies

NASA Astrophysics Data System (ADS)

Serafetinides, A. A.; Makropoulou, M.; Drakaki, E.

2008-12-01

Biophotonics techniques are applied to several fields in medicine and biology. The laser based techniques, such as the laser induced fluorescence (LIF) spectroscopy and the optical coherence tomography (OCT), are of particular importance in dermatology, where the laser radiation could be directly applied to the tissue target (e.g. skin). In addition, OCT resolves architectural tissue properties that might be useful as tumour discrimination parameters for skin as well as for ocular non-invasive visualization. Skin and ocular tissues are complex multilayered and inhomogeneous organs with spatially varying optical properties. This fact complicates the quantitative analysis of the fluorescence and/or light scattering spectra, even from the same tissue sample. To overcome this problem, mathematical simulation is applied for the investigation of the human tissue optical properties, in the visible/infrared range of the spectrum, resulting in a better discrimination of several tissue pathologies. In this work, we present i) a general view on biophotonics applications in diagnosis of human diseases, ii) some specific results on laser spectroscopy techniques, as LIF measurements, applied in arterial and skin pathologies and iii) some experimental and theoretical results on ocular OCT measurements. Regarding the LIF spectroscopy, we examined the autofluorescence properties of several human skin samples, excised from humans undergoing biopsy examination. A nitrogen laser was used as an excitation source, emitting at 337 nm (ultraviolet excitation). Histopathology examination of the samples was also performed, after the laser spectroscopy measurements and the results from the spectroscopic and medical analysis were compared, to differentiate malignancies, e.g. basal cell carcinoma tissue (BCC), from normal skin tissue. Regarding the OCT technique, we correlated human data, obtained from patients undergoing OCT examination, with Monte Carlo simulated cornea and retina tissues for diagnosis of ocular diseases.

High-hyperopia database, part I: clinical characterisation including morphometric (biometric) differentiation of posterior microphthalmos from nanophthalmos

PubMed Central

Relhan, N; Jalali, S; Pehre, N; Rao, H L; Manusani, U; Bodduluri, L

2016-01-01

Purpose To characterise and differentiate posterior microphthalmos (PM) and nanophthalmos (NO) using morphometric parameters. Patients and methods Consecutive case database of patients with hyperopia >+7.00 D sphere was analysed retrospectively for clinical and biometric characterisation. Thirty-eight consecutive high-hyperopic subjects (75 eyes) with axial lengths <20.5 mm underwent uniform comprehensive ocular evaluation. Twenty-five subjects were diagnosed as PM and 13 as NO based on the horizontal corneal diameter. Parameters analysed included visual acuity, refraction, horizontal corneal diameter, anterior chamber depth, lens thickness, axial length, fundus changes, and associated ocular pathology. Primary outcome measures: ocular biometry difference between PM and NO. Secondary outcome measures: differences in associated ocular pathologies between PM and NO. Results Hyperopia ranged from +7 to +17 D and was similar in the two groups. Lens thickness was statistically more in NO than in PM group (4.53±0.75 mm vs 3.82±0.48 mm, P <0.001), whereas anterior chamber depth was more in the PM than in NO group (3.26±0.36 mm, vs 2.59±0.37 mm, P<0.001). NO had higher association with angle-closure glaucoma (66.7% vs 0%) and pigmentary retinopathy (38.5 vs 8.0%) but lesser association with macular folds (0% vs 24%) as compared with PM. NO was associated with poorer visual acuity. Conclusion PM and NO have significant differences in lens thickness, anterior chamber depth, prevalence of glaucoma, pigmentary retinopathy, macular pathology, and visual acuity while being similar in hyperopic refraction. PMID:26493039

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

A thermographic study on eyes affected by Age-related Macular Degeneration: Comparison among various forms of the pathology and analysis of risk factors

NASA Astrophysics Data System (ADS)

Matteoli, Sara; Finocchio, Lucia; Biagini, Ilaria; Giacomelli, Giovanni; Sodi, Andrea; Corvi, Andrea; Virgili, Gianni; Rizzo, Stanislao

2016-05-01

The aims of this study are to investigate (1) the ocular thermographic profiles in eyes affected by Age related Macular Degeneration (AMD) and age-matched controls to detect possible hemodynamic abnormalities that could be involved in the pathogenesis of the disease, (2) whether any risk factors associated with the disease could affect the development of a form of AMD rather than another. Thirty-four eyes with Age-Related Maculopathy (ARM), 41 eyes with dry AMD, 60 eyes affected by wet AMD, and 74 eyes with fibrotic AMD were included in the study. The control group consisted of 48 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, systemic diseases and a body temperature higher than 37.5 °C. A total of 210 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The Ocular Surface Temperature (OST) of five ocular areas was calculated by means of an image processing technique from the infrared images. Two-sample t-test, one-way ANOVA test and multivariate analysis were used for statistical analyses. ANOVA analyses showed no significant differences among AMD groups (P-value > 0.05), however, OST in AMD patients was significantly lower than in controls (P-value < 0.0001). Smokers showed higher possibility (P-value = 0.012) of developing wet AMD instead of dry AMD. Infrared thermography may be a helpful, non-invasive and not time-consuming method to be used in the management of patients with this common degenerative maculopathy.

[Ocular manifestations of AIDS in Dakar].

PubMed

Ndoye, N B; Sow, P S; Ba, E A; Ndiaye, M R; Wade, A; Coll-Seck, A M

1993-01-01

In this prospective study undertaken between november 1989 and december 1991, the authors report their observations of ocular lesions seen in a cohort of 67 AIDS patients hospitalised in the Infectious Diseases department CHU Fann Dakar. Ocular lesions were discovered in 52.23%. These lesions were observed in both HIV-1 and HIV-2 positive patients, however they were much more common in the former group (77.14%). Rétinal pathology was by far the most frequently observed (63%) and yet classic retinis was not discovered in our series. We feel that the ophtalmologist should play a key role in the routine care of AIDS patients especially in surveillance of retinal changes.

Retinal Detachment: Torn or Detached Retina Symptoms

MedlinePlus

Subspecialties Cataract/Anterior Segment Comprehensive Ophthalmology Cornea/External Disease Glaucoma Neuro-Ophthalmology/Orbit Pediatric Ophthalmology/Strabismus Ocular Pathology/Oncology Oculoplastics/Orbit Refractive Management/Intervention Retina/Vitreous Uveitis ...

The ophthalmological observations in Caelius Aurelianus text on acute and on chronic diseases.

PubMed

Laios, Konstantinos; Moschos, Marilita; Androutsos, George

2016-12-01

Caelius Aurelianus' Latin translation, De morbis acutis et chronicis, of Soranus of Ephesus' original Greek work is a work devoted to internal medicine. Nevertheless, there are some observations about ocular pathologies which reveal the level of the knowledge at that time about the eye and their use as elements of pathological semiology.

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.

Professor Sergei Semjonovic Golovin (1866-1931): A Pioneer of Ocular Surgery.

PubMed

Moschos, Marilita M

2017-10-01

Professor Sergei Semjonovic Golovin (1866-1931) is considered as one of the founders of ophthalmology in Russia. He received a worldwide reputation thanks to his achievements in ocular surgery and pathology. He introduced new surgical techniques such as Golovin's operation (Exenteratio orbitosinualis), Golovin's osteoplastic frontal sinus operation, ligation of orbital veins, and opticociliary neurectomy. He also introduced his "cytotoxic theory" to interpret sympathetic ophthalmia. He was a reputable professor of ophthalmology.

Correction of Refractive Errors in Rhesus Macaques (Macaca mulatta) Involved in Visual Research

PubMed Central

Mitchell, Jude F; Boisvert, Chantal J; Reuter, Jon D; Reynolds, John H; Leblanc, Mathias

2014-01-01

Macaques are the most common animal model for studies in vision research, and due to their high value as research subjects, often continue to participate in studies well into old age. As is true in humans, visual acuity in macaques is susceptible to refractive errors. Here we report a case study in which an aged macaque demonstrated clear impairment in visual acuity according to performance on a demanding behavioral task. Refraction demonstrated bilateral myopia that significantly affected behavioral and visual tasks. Using corrective lenses, we were able to restore visual acuity. After correction of myopia, the macaque's performance on behavioral tasks was comparable to that of a healthy control. We screened 20 other male macaques to assess the incidence of refractive errors and ocular pathologies in a larger population. Hyperopia was the most frequent ametropia but was mild in all cases. A second macaque had mild myopia and astigmatism in one eye. There were no other pathologies observed on ocular examination. We developed a simple behavioral task that visual research laboratories could use to test visual acuity in macaques. The test was reliable and easily learned by the animals in 1 d. This case study stresses the importance of screening macaques involved in visual science for refractive errors and ocular pathologies to ensure the quality of research; we also provide simple methodology for screening visual acuity in these animals. PMID:25427343

Correction of refractive errors in rhesus macaques (Macaca mulatta) involved in visual research.

PubMed

Mitchell, Jude F; Boisvert, Chantal J; Reuter, Jon D; Reynolds, John H; Leblanc, Mathias

2014-08-01

Macaques are the most common animal model for studies in vision research, and due to their high value as research subjects, often continue to participate in studies well into old age. As is true in humans, visual acuity in macaques is susceptible to refractive errors. Here we report a case study in which an aged macaque demonstrated clear impairment in visual acuity according to performance on a demanding behavioral task. Refraction demonstrated bilateral myopia that significantly affected behavioral and visual tasks. Using corrective lenses, we were able to restore visual acuity. After correction of myopia, the macaque's performance on behavioral tasks was comparable to that of a healthy control. We screened 20 other male macaques to assess the incidence of refractive errors and ocular pathologies in a larger population. Hyperopia was the most frequent ametropia but was mild in all cases. A second macaque had mild myopia and astigmatism in one eye. There were no other pathologies observed on ocular examination. We developed a simple behavioral task that visual research laboratories could use to test visual acuity in macaques. The test was reliable and easily learned by the animals in 1 d. This case study stresses the importance of screening macaques involved in visual science for refractive errors and ocular pathologies to ensure the quality of research; we also provide simple methodology for screening visual acuity in these animals.

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

Pharmacologic Activation of Wnt Signaling by Lithium Normalizes Retinal Vasculature in a Murine Model of Familial Exudative Vitreoretinopathy.

PubMed

Wang, Zhongxiao; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Favazza, Tara L; Morss, Peyton C; Saba, Nicholas J; Fredrick, Thomas W; He, Xi; Akula, James D; Chen, Jing

2016-10-01

Familial exudative vitreoretinopathy (FEVR) is characterized by delayed retinal vascular development, which promotes hypoxia-induced pathologic vessels. In severe cases FEVR may lead to retinal detachment and visual impairment. Genetic studies linked FEVR with mutations in Wnt signaling ligand or receptors, including low-density lipoprotein receptor-related protein 5 (LRP5) gene. Here, we investigated ocular pathologies in a Lrp5 knockout (Lrp5(-/-)) mouse model of FEVR and explored whether treatment with a pharmacologic Wnt activator lithium could bypass the genetic defects, thereby protecting against eye pathologies. Lrp5(-/-) mice displayed significantly delayed retinal vascular development, absence of deep layer retinal vessels, leading to increased levels of vascular endothelial growth factor and subsequent pathologic glomeruloid vessels, as well as decreased inner retinal visual function. Lithium treatment in Lrp5(-/-) mice significantly restored the delayed development of retinal vasculature and the intralaminar capillary networks, suppressed formation of pathologic glomeruloid structures, and promoted hyaloid vessel regression. Moreover, lithium treatment partially rescued inner-retinal visual function and increased retinal thickness. These protective effects of lithium were largely mediated through restoration of canonical Wnt signaling in Lrp5(-/-) retina. Lithium treatment also substantially increased vascular tubular formation in LRP5-deficient endothelial cells. These findings suggest that pharmacologic activation of Wnt signaling may help treat ocular pathologies in FEVR and potentially other defective Wnt signaling-related diseases. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A survey on computer aided diagnosis for ocular diseases

PubMed Central

2014-01-01

Background Computer Aided Diagnosis (CAD), which can automate the detection process for ocular diseases, has attracted extensive attention from clinicians and researchers alike. It not only alleviates the burden on the clinicians by providing objective opinion with valuable insights, but also offers early detection and easy access for patients. Method We review ocular CAD methodologies for various data types. For each data type, we investigate the databases and the algorithms to detect different ocular diseases. Their advantages and shortcomings are analyzed and discussed. Result We have studied three types of data (i.e., clinical, genetic and imaging) that have been commonly used in existing methods for CAD. The recent developments in methods used in CAD of ocular diseases (such as Diabetic Retinopathy, Glaucoma, Age-related Macular Degeneration and Pathological Myopia) are investigated and summarized comprehensively. Conclusion While CAD for ocular diseases has shown considerable progress over the past years, the clinical importance of fully automatic CAD systems which are able to embed clinical knowledge and integrate heterogeneous data sources still show great potential for future breakthrough. PMID:25175552

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.

[Autologous serum tears: Long-term treatment in dry eye syndrome].

PubMed

Beylerian, M; Lazaro, M; Magalon, J; Veran, J; Darque, A; Grimaud, F; Stolowy, N; Beylerian, H; Sabatier, F; Hoffart, L

2018-03-01

Dry eye disease is a multifactorial pathology of the ocular surface. The high incidence of this pathology, as well as its significant impact on quality of life and vision and its financial cost, makes it a real public health problem. While the treatment of mild cases is generally simple and effective, treatment of severe forms is often disappointing. The use of autologous serum tears (AST) represents a therapeutic alternative for the most severe cases. The purpose of our study is to evaluate the efficacy of long-term AST treatment in patients with severe dry eye disease refractory to conventional treatment or secondary to systemic diseases such as Sjögren's syndrome or Graft versus Host disease (GVH), or ocular pathologies such as neurotrophic keratitis, chemical burns and ocular cicatricial pemphigoid. This is a monocentric retrospective observational study conducted on 47 patients, with 83 eyes treated with autologous serum eye drops for isolated or secondary dry eye disease at the Marseille Public Hospitals between April 2014 and April 2017. The patients' subjective symptoms (ocular surface disease index [OSDI] score), their degree of satisfaction and the side effects were collected using questionnaires. Tear Break Up Time (BUT) and Schirmer scores were noted. A clinical evaluation based on fluorescein staining (Oxford score) was carried out prior to treatment with AST at P0 followed by 5 periods: P1 (between 1 and 3 months), P2 (3 to 9 months), P3 (9 to 15 months), P4 (15 months to 24 months), and P5 (>24 months). Out of the 83 eyes treated, the mean age was 54.39±21.56. There were 20 males (42.55 %) and 27 females (57.44 %); treatment indications consisted mainly of 25.53 % GVH, 21.27 % severe dry eye disease and 19.14 % Sjögren syndrome. The mean duration of follow-up was 9.82 months±15.50. The OSDI score decreased by 19.32 points±29.37 (P<0.05) between P0 and P1 and by 23.06 points±18.41 (P<0.05) between P0 and P4. The Oxford clinical score showed a significant decrease by the third month of treatment, between P0 and P2, by 1.32 points±1.76 (P<0.05). The Schirmer test and the BUT also showed an improvement in dry eye symptoms over time with AST, significantly at P1 (P<0.05). Complementary biological analyzes on the composition of AST are under way in order to identify predictive factors of effectiveness; patients not responding to AST treatment might respond to allogeneic serum from healthy donor cord blood. On this first series of 83 eyes treated with ASD, clinical efficacy was noted in most of the patients. No infectious complications were reported, and the satisfaction rate was very high. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Spdef null mice lack conjunctival goblet cells and provide a model of dry eye.

PubMed

Marko, Christina K; Menon, Balaraj B; Chen, Gang; Whitsett, Jeffrey A; Clevers, Hans; Gipson, Ilene K

2013-07-01

Goblet cell numbers decrease within the conjunctival epithelium in drying and cicatrizing ocular surface diseases. Factors regulating goblet cell differentiation in conjunctival epithelium are unknown. Recent data indicate that the transcription factor SAM-pointed domain epithelial-specific transcription factor (Spdef) is essential for goblet cell differentiation in tracheobronchial and gastrointestinal epithelium of mice. Using Spdef(-/-) mice, we determined that Spdef is required for conjunctival goblet cell differentiation and that Spdef(-/-) mice, which lack conjunctival goblet cells, have significantly increased corneal surface fluorescein staining and tear volume, a phenotype consistent with dry eye. Microarray analysis of conjunctival epithelium in Spdef(-/-) mice revealed down-regulation of goblet cell-specific genes (Muc5ac, Tff1, Gcnt3). Up-regulated genes included epithelial cell differentiation/keratinization genes (Sprr2h, Tgm1) and proinflammatory genes (Il1-α, Il-1β, Tnf-α), all of which are up-regulated in dry eye. Interestingly, four Wnt pathway genes were down-regulated. SPDEF expression was significantly decreased in the conjunctival epithelium of Sjögren syndrome patients with dry eye and decreased goblet cell mucin expression. These data demonstrate that Spdef is required for conjunctival goblet cell differentiation and down-regulation of SPDEF may play a role in human dry eye with goblet cell loss. Spdef(-/-) mice have an ocular surface phenotype similar to that in moderate dry eye, providing a new, more convenient model for the disease. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Validity and Acceptance of Color Vision Testing on Smartphones.

PubMed

Ozgur, Omar K; Emborgo, Trisha S; Vieyra, Mark B; Huselid, Rebecca F; Banik, Rudrani

2018-03-01

Ishihara color plates (ICP) are the most commonly used color vision test (CVT) worldwide. With the advent of new technologies, attempts have been made to streamline the process of CVT. As hardware and software evolve, smartphone-based testing modalities may aid ophthalmologists in performing more efficient ophthalmic examinations. We assess the validity of smartphone color vision testing (CVT) by comparing results using the Eye Handbook (EHB) CVT application with standard Ishihara color plates (ICP). Prospective case-control study of subjects 18 years and older with visual acuity of 20/100 or better at 14 inches. The study group included patients with any ocular pathology. The color vision deficient (CVD) group was patients who failed more than 2 plates. The control group had no known ocular pathology. CVT was performed with both ICP and EHB under standardized background illuminance. Eleven plates were tested with each modality. Validity of EHB CVT and acceptance of EHB CVT were analyzed. Statistical analyses were performed using Bland-Altman plot with limits of agreement (LOA) at the 95th percentile of differences in score, independent samples t tests with 95% confidence interval (CI), and Pearson χ tests. The Bland-Altman plot showed agreement between correct number of plates in EHB and ICP for the study subjects (bias, -0.25; LOA, -1.92 to 1.42). Agreement was also observed between the correct number of plates in EHB and ICP for the controls (bias, -0.01; LOA, -0.61 to 0.59) and CVD (bias, -0.50; LOA, -4.64 to 3.64) subjects. The sensitivity of EHB was 0.92 (95% CI 0.76-1.07) and the specificity of EHB was 1.00 (95% CI 1.00-1.00). Fifty-nine percent preferred EHB, 12% preferred ICP, and 29% had no preference. In healthy controls and patients with ocular pathology, there was an agreement of CVT results comparing EHB with ICP. Overall, the majority preferred EHB to ICP. These findings demonstrate that further testing is required to understand and improve the validity of smartphone CVT in subjects with ocular pathology.

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.

Tear film and ocular surface assessment in psoriasis.

PubMed

Aragona, Emanuela; Rania, Laura; Postorino, Elisa Imelde; Interdonato, Alberto; Giuffrida, Roberta; Cannavò, Serafinella Patrizia; Puzzolo, Domenico; Aragona, Pasquale

2018-03-01

Psoriasis is a skin disease with also systemic involvement: its impact on the eye is not well established and often clinically underestimated. Aim of this study was to investigate the presence of ocular discomfort symptoms and of ocular surface changes in a population of patients with psoriasis. For this cross-sectional, comparative study, 66 patients with psoriasis were subdivided according to the presence of arthritis and to the use of biological therapy. All patients underwent clinical evaluation with the following tests: Ocular Surface Disease Index Questionnaire, Tearscope examination, meibometry, tear film breakup time, corneal and conjunctival fluorescein staining, Schirmer I test, corneal aesthesiometry, meibomian gland dysfunction (MGD) assessment and conjunctival impression cytology. 28 healthy subjects were also enrolled and treated with the same clinical tests. A statistical analysis of the results was performed. Patients with psoriasis showed a significant deterioration of the ocular surface tests, if compared with healthy subjects, demonstrated by tear film lipid layer alteration, tear film instability, corneal and conjunctival epithelial suffering and mild squamous metaplasia at impression cytology. No differences were found in ocular surface test results of the psoriatic group when patients were divided according to the presence of arthritis, whereas the anti-inflammatory treatment with biological drugs demonstrated a significant improvement of corneal stain and MGD. Our findings suggest that the ocular surface involvement in patients with psoriasis indicates the need of periodic ophthalmological examinations to diagnose the condition and allow a proper treatment, so contributing to the amelioration of patients' quality of life. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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.

Quantitative Fourier Domain Optical Coherence Tomography Imaging of the Ocular Anterior Segment

NASA Astrophysics Data System (ADS)

McNabb, Ryan Palmer

Clinical imaging within ophthalmology has had transformative effects on ocular health over the last century. Imaging has guided clinicians in their pharmaceutical and surgical treatments of macular degeneration, glaucoma, cataracts and numerous other pathologies. Many of the imaging techniques currently used are photography based and are limited to imaging the surface of ocular structures. This limitation forces clinicians to make assumptions about the underlying tissue which may reduce the efficacy of their diagnoses. Optical coherence tomography (OCT) is a non-invasive, non-ionizing imaging modality that has been widely adopted within the field of ophthalmology in the last 15 years. As an optical imaging technique, OCT utilizes low-coherence interferometry to produce micron-scale three-dimensional datasets of a tissue's structure. Much of the human body consists of tissues that significantly scatter and attenuate optical signals limiting the imaging depth of OCT in those tissues to only 1-2mm. However, the ocular anterior segment is unique among human tissue in that it is primarily transparent or translucent. This allows for relatively deep imaging of tissue structure with OCT and is no longer limited by the optical scattering properties of the tissue. This goal of this work is to develop methods utilizing OCT that offer the potential to reduce the assumptions made by clinicians in their evaluations of their patients' ocular anterior segments. We achieved this by first developing a method to reduce the effects of patient motion during OCT volume acquisitions allowing for accurate, three dimensional measurements of corneal shape. Having accurate corneal shape measurements then allowed us to determine corneal spherical and astigmatic refractive contribution in a given individual. This was then validated in a clinical study that showed OCT better measured refractive change due to surgery than other clinical devices. Additionally, a method was developed to combine the clinical evaluation of the iridocorneal angle through gonioscopy with OCT.

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

Hydrosilylated Porous Silicon Particles Function as an Intravitreal Drug Delivery System for Daunorubicin

PubMed Central

Hartmann, Kathrin I.; Nieto, Alejandra; Wu, Elizabeth C.; Freeman, William R.; Kim, Jae Suk; Chhablani, Jay; Sailor, Michael J.

2013-01-01

Abstract Purpose To evaluate in vivo ocular safety of an intravitreal hydrosilylated porous silicon (pSi) drug delivery system along with the payload of daunorubicin (DNR). Methods pSi microparticles were prepared from the electrochemical etching of highly doped, p-type Si wafers and an organic linker was attached to the Si-H terminated inner surface of the particles by thermal hydrosilylation of undecylenic acid. DNR was bound to the carboxy terminus of the linker as a drug-loading strategy. DNR release from hydrosilylated pSi particles was confirmed in the excised rabbit vitreous using liquid chromatography–electrospray ionization–multistage mass spectrometry. Both empty and DNR-loaded hydrosilylated pSi particles were injected into the rabbit vitreous and the degradation and safety were studied for 6 months. Results The mean pSi particle size was 30×46×15 μm with an average pore size of 15 nm. Drug loading was determined as 22 μg per 1 mg of pSi particles. An ex vivo drug release study showed that intact DNR was detected in the rabbit vitreous. An in vivo ocular toxicity study did not reveal clinical or pathological evidence of any toxicity during a 6-month observation. Hydrosilylated pSi particles, either empty or loaded with DNR, demonstrated a slow elimination kinetics from the rabbit vitreous without ocular toxicity. Conclusions Hydrosilylated pSi particles can host a large quantity of DNR by a covalent loading strategy and DNR can be slowly released into the vitreous without ocular toxicity, which would appear if an equivalent quantity of free drug was injected. PMID:23448595

Nanoparticles for Retinal Gene Therapy

PubMed Central

Conley, Shannon M.; Naash, Muna I.

2010-01-01

Ocular gene therapy is becoming a well-established field. Viral gene therapies for the treatment of Leber’s congentinal amaurosis (LCA) are in clinical trials, and many other gene therapy approaches are being rapidly developed for application to diverse ophthalmic pathologies. Of late, development of non-viral gene therapies has been an area of intense focus and one technology, polymer-compacted DNA nanoparticles, is especially promising. However, development of pharmaceutically and clinically viable therapeutics depends not only on having an effective and safe vector but also on a practical treatment strategy. Inherited retinal pathologies are caused by mutations in over 220 genes, some of which contain over 200 individual disease-causing mutations, which are individually very rare. This review will focus on both the progress and future of nanoparticles and also on what will be required to make them relevant ocular pharmaceutics. PMID:20452457

Space Flight-Associated Neuro-ocular Syndrome.

PubMed

Lee, Andrew G; Mader, Thomas H; Gibson, C Robert; Tarver, William

2017-09-01

New and unique physiologic and pathologic systemic and neuro-ocular responses have been documented in astronauts during and after long-duration space flight. Although the precise cause remains unknown, space flight-associated neuro-ocular syndrome (SANS) has been adopted as an appropriate descriptive term. The Space Medicine Operations Division of the US National Aeronautics and Space Administration (NASA) has documented the variable occurrence of SANS in astronauts returning from long-duration space flight on the International Space Station. These clinical findings have included unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts. The clinical findings of SANS have been correlated with structural changes on intraorbital and intracranial magnetic resonance imaging and in-flight and terrestrial ultrasonographic studies and ocular optical coherence tomography. Further study of SANS is ongoing for consideration of future manned missions to space, including a return trip to the moon or Mars.

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.

Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma

PubMed Central

Zode, Gulab S.; Sharma, Arti B.; Lin, Xiaolei; Searby, Charles C.; Bugge, Kevin; Kim, Gun Hee; Clark, Abbot F.; Sheffield, Val C.

2014-01-01

Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open-angle glaucoma (POAG). The underlying pathology of glucocorticoid-induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid-induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0.1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid-induced glaucoma in human patients. Furthermore, dexamethasone-induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma. PMID:24691439

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.

ADAM9 Is Involved in Pathological Retinal Neovascularization▿

PubMed Central

Guaiquil, Victor; Swendeman, Steven; Yoshida, Tsunehiko; Chavala, Sai; Campochiaro, Peter A.; Blobel, Carl P.

2009-01-01

Pathological ocular neovascularization, caused by diabetic retinopathy, age-related macular degeneration, or retinopathy of prematurity, is a leading cause of blindness, yet much remains to be learned about its underlying causes. Here we used oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) to assess the contribution of the metalloprotease-disintegrin ADAM9 to ocular neovascularization in mice. Pathological neovascularization in both the OIR and CNV models was significantly reduced in Adam9−/− mice compared to wild-type controls. In addition, the level of ADAM9 expression was strongly increased in endothelial cells in pathological vascular tufts in the OIR model. Moreover, tumor growth from heterotopically injected B16F0 melanoma cells was reduced in Adam9−/− mice compared to controls. In cell-based assays, the overexpression of ADAM9 enhanced the ectodomain shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin, so the enhanced expression of ADAM9 could potentially affect pathological neovascularization by increasing the shedding of these and other membrane proteins from endothelial cells. Finally, we provide the first evidence for the upregulation of ADAM9-dependent shedding by reactive oxygen species, which in turn are known to play a critical role in OIR. Collectively, these results suggest that ADAM9 could be an attractive target for the prevention of proliferative retinopathies, CNV, and cancer. PMID:19273593

ADAM9 is involved in pathological retinal neovascularization.

PubMed

Guaiquil, Victor; Swendeman, Steven; Yoshida, Tsunehiko; Chavala, Sai; Campochiaro, Peter A; Blobel, Carl P

2009-05-01

Pathological ocular neovascularization, caused by diabetic retinopathy, age-related macular degeneration, or retinopathy of prematurity, is a leading cause of blindness, yet much remains to be learned about its underlying causes. Here we used oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) to assess the contribution of the metalloprotease-disintegrin ADAM9 to ocular neovascularization in mice. Pathological neovascularization in both the OIR and CNV models was significantly reduced in Adam9(-/-) mice compared to wild-type controls. In addition, the level of ADAM9 expression was strongly increased in endothelial cells in pathological vascular tufts in the OIR model. Moreover, tumor growth from heterotopically injected B16F0 melanoma cells was reduced in Adam9(-/-) mice compared to controls. In cell-based assays, the overexpression of ADAM9 enhanced the ectodomain shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin, so the enhanced expression of ADAM9 could potentially affect pathological neovascularization by increasing the shedding of these and other membrane proteins from endothelial cells. Finally, we provide the first evidence for the upregulation of ADAM9-dependent shedding by reactive oxygen species, which in turn are known to play a critical role in OIR. Collectively, these results suggest that ADAM9 could be an attractive target for the prevention of proliferative retinopathies, CNV, and cancer.

Canine ocular protothecosis: A review of 14 cases.

PubMed

Shank, Alba Maria M; Dubielzig, Richard D; Teixeira, Leandro B C

2015-09-01

To examine a series of 14 cases of canine ocular protothecosis from archived cases from the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW), and compare gross and histologic findings. Archival records from COPLOW were searched for canine cases of ocular protothecosis. Fourteen cases that contained matching criteria were identified, and gross and histologic findings, and clinical records for each case were tabulated, examined, and compared (2001-2013). Of the 14 cases identified, six had evidence of systemic disease, as per clinical history. Two of the 14 cases had Prototheca identified via cytology of ocular fluid or retinal exudate; in the remainder of cases, Prototheca identified via cytology of ocular fluid or retinal exudate in the remaining 12 cases, Prototheca was identified upon histologic examination of the submitted globe(s). Presenting ocular clinical signs were variable and nonspecific. Duration of ocular clinical signs varied from days to months. Fundoscopically, white membranes or plaques were identified on or around the retina in five cases. Retinal detachment was identified in 13 of the 14 submitted globes on gross examination following fixation and sectioning. The predominant histologic finding was granulomatous chorioretinitis with retinal detachment, with variable numbers of Prototheca within the inflammatory infiltrate. Due to the nonspecific nature of the ocular signs, a diagnosis of protothecosis generally is not made until enucleation and histopathologic examination of the globe(s). Retinal detachment and blindness were common. Cytologic sampling of retinal plaques and exudate may provide a rapid way to identify Prototheca. © 2014 American College of Veterinary Ophthalmologists.

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.

Visual and Ocular Manifestations of Alzheimer’s Disease and Their Use as Biomarkers for Diagnosis and Progression

PubMed Central

Javaid, Fatimah Zara; Brenton, Jonathan; Guo, Li; Cordeiro, Maria F.

2016-01-01

Alzheimer’s disease (AD) is the most common form of dementia affecting the growing aging population today, with prevalence expected to rise over the next 35 years. Clinically, patients exhibit a progressive decline in cognition, memory, and social functioning due to deposition of amyloid β (Aβ) protein and intracellular hyperphosphorylated tau protein. These pathological hallmarks of AD are measured either through neuroimaging, cerebrospinal fluid analysis, or diagnosed post-mortem. Importantly, neuropathological progression occurs in the eye as well as the brain, and multiple visual changes have been noted in both human and animal models of AD. The eye offers itself as a transparent medium to cerebral pathology and has thus potentiated the development of ocular biomarkers for AD. The use of non-invasive screening, such as retinal imaging and visual testing, may enable earlier diagnosis in the clinical setting, minimizing invasive and expensive investigations. It also potentially improves disease management and quality of life for AD patients, as an earlier diagnosis allows initiation of medication and treatment. In this review, we explore the evidence surrounding ocular changes in AD and consider the biomarkers currently in development for early diagnosis. PMID:27148157

The Eye As a Biomarker for Alzheimer's Disease

PubMed Central

Lim, Jeremiah K. H.; Li, Qiao-Xin; He, Zheng; Vingrys, Algis J.; Wong, Vickie H. Y.; Currier, Nicolas; Mullen, Jamie; Bui, Bang V.; Nguyen, Christine T. O.

2016-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in dementia and eventual death. It is the leading cause of dementia and the number of cases are projected to rise in the next few decades. Pathological hallmarks of AD include the presence of hyperphosphorylated tau and amyloid protein deposition. Currently, these pathological biomarkers are detected either through cerebrospinal fluid analysis, brain imaging or post-mortem. Though effective, these methods are not widely available due to issues such as the difficulty in acquiring samples, lack of infrastructure or high cost. Given that the eye possesses clear optics and shares many neural and vascular similarities to the brain, it offers a direct window to cerebral pathology. These unique characteristics lend itself to being a relatively inexpensive biomarker for AD which carries the potential for wide implementation. The development of ocular biomarkers can have far implications in the discovery of treatments which can improve the quality of lives of patients. In this review, we consider the current evidence for ocular biomarkers in AD and explore potential future avenues of research in this area. PMID:27909396

Acquired color vision deficiency.

PubMed

Simunovic, Matthew P

2016-01-01

Acquired color vision deficiency occurs as the result of ocular, neurologic, or systemic disease. A wide array of conditions may affect color vision, ranging from diseases of the ocular media through to pathology of the visual cortex. Traditionally, acquired color vision deficiency is considered a separate entity from congenital color vision deficiency, although emerging clinical and molecular genetic data would suggest a degree of overlap. We review the pathophysiology of acquired color vision deficiency, the data on its prevalence, theories for the preponderance of acquired S-mechanism (or tritan) deficiency, and discuss tests of color vision. We also briefly review the types of color vision deficiencies encountered in ocular disease, with an emphasis placed on larger or more detailed clinical investigations. Copyright © 2016 Elsevier Inc. All rights reserved.

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 cholesterol-dependent cytolysin pneumolysin from Streptococcus pneumoniae binds to lipid raft microdomains in human corneal epithelial cells.

PubMed

Taylor, Sidney D; Sanders, Melissa E; Tullos, Nathan A; Stray, Stephen J; Norcross, Erin W; McDaniel, Larry S; Marquart, Mary E

2013-01-01

Streptococcus pneumoniae (pneumococcus) is an opportunistic bacterial pathogen responsible for causing several human diseases including pneumonia, meningitis, and otitis media. Pneumococcus is also a major cause of human ocular infections and is commonly isolated in cases of bacterial keratitis, an infection of the cornea. The ocular pathology that occurs during pneumococcal keratitis is partly due to the actions of pneumolysin (Ply), a cholesterol-dependent cytolysin produced by pneumococcus. The lytic mechanism of Ply is a three step process beginning with surface binding to cholesterol. Multiple Ply monomers then oligomerize to form a prepore. The prepore then undergoes a conformational change that creates a large pore in the host cell membrane, resulting in cell lysis. We engineered a collection of single amino acid substitution mutants at residues (A370, A406, W433, and L460) that are crucial to the progression of the lytic mechanism and determined the effects that these mutations had on lytic function. Both Ply(WT) and the mutant Ply molecules (Ply(A370G), Ply(A370E), Ply(A406G), Ply(A406E), Ply(W433G), Ply(W433E), Ply(W433F), Ply(L460G), and Ply(L460E)) were able to bind to the surface of human corneal epithelial cells (HCECs) with similar efficiency. Additionally, Ply(WT) localized to cholesterol-rich microdomains on the HCEC surface, however, only one mutant (Ply(A370G)) was able to duplicate this behavior. Four of the 9 mutant Ply molecules (Ply(A370E), Ply(W433G), Ply(W433E), and Ply(L460E)) were deficient in oligomer formation. Lastly, all of the mutant Ply molecules, except Ply(A370G), exhibited significantly impaired lytic activity on HCECs. The other 8 mutants all experienced a reduction in lytic activity, but 4 of the 8 retained the ability to oligomerize. A thorough understanding of the molecular interactions that occur between Ply and the target cell, could lead to targeted treatments aimed to reduce the pathology observed during pneumococcal keratitis.

The Cholesterol-Dependent Cytolysin Pneumolysin from Streptococcus pneumoniae Binds to Lipid Raft Microdomains in Human Corneal Epithelial Cells

PubMed Central

Taylor, Sidney D.; Sanders, Melissa E.; Tullos, Nathan A.; Stray, Stephen J.; Norcross, Erin W.; McDaniel, Larry S.; Marquart, Mary E.

2013-01-01

Streptococcus pneumoniae (pneumococcus) is an opportunistic bacterial pathogen responsible for causing several human diseases including pneumonia, meningitis, and otitis media. Pneumococcus is also a major cause of human ocular infections and is commonly isolated in cases of bacterial keratitis, an infection of the cornea. The ocular pathology that occurs during pneumococcal keratitis is partly due to the actions of pneumolysin (Ply), a cholesterol-dependent cytolysin produced by pneumococcus. The lytic mechanism of Ply is a three step process beginning with surface binding to cholesterol. Multiple Ply monomers then oligomerize to form a prepore. The prepore then undergoes a conformational change that creates a large pore in the host cell membrane, resulting in cell lysis. We engineered a collection of single amino acid substitution mutants at residues (A370, A406, W433, and L460) that are crucial to the progression of the lytic mechanism and determined the effects that these mutations had on lytic function. Both PlyWT and the mutant Ply molecules (PlyA370G, PlyA370E, PlyA406G, PlyA406E, PlyW433G, PlyW433E, PlyW433F, PlyL460G, and PlyL460E) were able to bind to the surface of human corneal epithelial cells (HCECs) with similar efficiency. Additionally, PlyWT localized to cholesterol-rich microdomains on the HCEC surface, however, only one mutant (PlyA370G) was able to duplicate this behavior. Four of the 9 mutant Ply molecules (PlyA370E, PlyW433G, PlyW433E, and PlyL460E) were deficient in oligomer formation. Lastly, all of the mutant Ply molecules, except PlyA370G, exhibited significantly impaired lytic activity on HCECs. The other 8 mutants all experienced a reduction in lytic activity, but 4 of the 8 retained the ability to oligomerize. A thorough understanding of the molecular interactions that occur between Ply and the target cell, could lead to targeted treatments aimed to reduce the pathology observed during pneumococcal keratitis. PMID:23577214

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.

Emerging therapies in allergic conjunctivitis and dry eye syndrome.

PubMed

Nye, Michael; Rudner, Shara; Bielory, Leonard

2013-08-01

Inflammatory disorders of the anterior surface of the eye consist of a spectrum of disorders that range from ocular allergy, dry eye syndrome (DES), and various infections. They exhibit similar pathological profiles, but have divergent immune mechanisms with some overlap. A number of novel treatments are currently being studied that capitalize on the growing understanding of underlying immunopathophysiology. The goal of this review is to examine the emerging pipeline for noninfectious inflammatory disorders of the anterior surface of the eye - primarily allergic conjunctivitis (AC) and DES - in light of the recent basic science discoveries that have fueled their development. Novel molecules for the treatment of AC and DES from clinicaltrials.gov as well as recently filed patents for new molecular entities were reviewed from PUBMED and OVID. Significant progress toward targeted treatments for AC and DES has become increasingly reliant on understanding the immunomodulatory and inflammatory mechanisms of the conjunctiva.

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.

Eclectic Ocular Comorbidities and Systemic Diseases with Eye Involvement: A Review.

PubMed

Pinazo-Durán, María D; Zanón-Moreno, Vicente; García-Medina, José J; Arévalo, J Fernando; Gallego-Pinazo, Roberto; Nucci, Carlo

2016-01-01

Coexistence of several ocular diseases is more frequent than suspected. In spite of the refractive errors, one or more of the following can be detected simultaneously: glaucoma, cataracts, uveitis, age-related macular degeneration, and dry eyes. In addition, as people age, ocular comorbidities are much more usually seen. Specific diseases are openly acknowledged to affect the eyes and vision, such as diabetes mellitus, hypertension blood pressure, arthritis, hyperthyroidism, neurodegenerative disorders, hematologic malignancies, and/or systemic infections. Recent advances in early diagnosis and therapy of the ophthalmic pathologies have reinforced patient options to prevent visual impairment and blindness. Because of this, it is essential not to overlook sight-threatening conditions such as the ocular comorbidities and/or the eye involvement in the context of systemic disorders. Moreover, the important role of the multidisciplinary cooperation to improve and sustain management of patients affected with eclectic ocular comorbidities and/or systemic disorders with eye repercussion is specifically addressed. This review intends to shed light on these topics to help in making opportune diagnosis and appropriately managing the affected patients.

Eclectic Ocular Comorbidities and Systemic Diseases with Eye Involvement: A Review

PubMed Central

Zanón-Moreno, Vicente; García-Medina, José J.; Arévalo, J. Fernando; Gallego-Pinazo, Roberto; Nucci, Carlo

2016-01-01

Coexistence of several ocular diseases is more frequent than suspected. In spite of the refractive errors, one or more of the following can be detected simultaneously: glaucoma, cataracts, uveitis, age-related macular degeneration, and dry eyes. In addition, as people age, ocular comorbidities are much more usually seen. Specific diseases are openly acknowledged to affect the eyes and vision, such as diabetes mellitus, hypertension blood pressure, arthritis, hyperthyroidism, neurodegenerative disorders, hematologic malignancies, and/or systemic infections. Recent advances in early diagnosis and therapy of the ophthalmic pathologies have reinforced patient options to prevent visual impairment and blindness. Because of this, it is essential not to overlook sight-threatening conditions such as the ocular comorbidities and/or the eye involvement in the context of systemic disorders. Moreover, the important role of the multidisciplinary cooperation to improve and sustain management of patients affected with eclectic ocular comorbidities and/or systemic disorders with eye repercussion is specifically addressed. This review intends to shed light on these topics to help in making opportune diagnosis and appropriately managing the affected patients. PMID:27051666

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.

Ultrasonography of the eye and orbit.

PubMed

Eisenberg, H M

1985-11-01

The eye and orbit are excellent subjects for ultrasonic evaluation. Examination and interpretation are relatively simple procedures. The normal ultrasonic anatomy of the eye and orbit is presented. Some examples of ocular and orbital pathology are discussed also.

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.

Quantitative reflection spectroscopy at the human ocular fundus

NASA Astrophysics Data System (ADS)

Hammer, Martin; Schweitzer, Dietrich

2002-01-01

A new model of the reflection of the human ocular fundus on the basis of the adding-doubling method, an approximate solution of the radiative transport equation, is described. This model enables the calculation of the concentrations of xanthophyll in the retina, of melanin in the retinal pigment epithelium and the choroid, and of haemoglobin in the choroid from fundus reflection spectra. The concentration values found in 12 healthy subjects are in excellent agreement with published data. In individual cases of pathologic fundus alterations, possible benefits to the ophthalmologic diagnostics are demonstrated.

Vision Profile and Ocular Characteristics of Special Olympics Athletes: Report from India.

PubMed

Gothwal, Vijaya K; Sumalini, Rebecca; Narasaiah, Asa; Panda, Soumya

2017-08-01

Previous reports, albeit isolated, of vision and ocular screening of athletes with intellectual disability participating in the Special Olympics, UK, indicated high rates of refractive error and ocular morbidity; however, there have been no reports of similar sports events for this population from India. This study set out to evaluate the vision profile and ocular characteristics of athletes with intellectual disability attending the Special Olympics Lions Club International Opening Eyes (SOLCIOE) event in 2012 in India. A cross-sectional study was conducted, where a protocol-based ophthalmological assessment was performed by trained optometrists at a tertiary eye care center. Overall, 172 athletes (mean age 18.6 years, 70% male) with intellectual disability participated, and 138 (80%) were able to cooperate for complete or nearly complete vision and ocular assessment. A total of 56 (32%) had never had a previous vision or ocular health status examination. A total of 46 (32%) presented with low vision (World Health Organization definition <6/18 to 3/60 in the better eye), 21% needed a first or updated spectacle prescription, and 28% had significant ocular pathology as the cause of visual loss. The proportions of refractive errors and ocular disorders in athletes with intellectual disability attending the SOLCIOE program in South India are similar to those reported for able-bodied school-aged children in urban and rural India. Like that of their able-bodied peers, the visual needs of children with intellectual disability are also not adequately being met.

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.

Ocular injuries from fireworks: the 11-year experience of a US level I trauma center.

PubMed

Chang, I T; Prendes, M A; Tarbet, K J; Amadi, A J; Chang, S-H; Shaftel, S S

2016-10-01

PurposeCharacterize ocular trauma and visual outcomes from firework injuries at a level I trauma center.MethodsRetrospective review of all firework injuries at Harborview Medical Center between 2003 and 2013.ResultsThree hundred and twenty-seven patients sustained firework injuries, of which 100 (31%) sustained ocular injuries. The average age of all patients who sustained fireworks injuries was 24.2 years, 89% were male and 54% of injuries occurred within 48 h of 4 July. Ocular injuries were most commonly caused by mortars (24%) and rockets (22%). Rockets were associated with four times the frequency of ocular injuries as compared with non-ocular injuries (P<0.001). Spectators were more likely to sustain ocular injuries than non-ocular injuries (P=0.001). The most common injuries sustained were corneal abrasions (67%), hyphemas (42%), eyelid injuries (39%), and ruptured globes (17%). Twenty-eight percent of patients with ocular injuries required surgical intervention. Ruptured globes occurred in 17% of patients, with the majority being complex corneoscleral lacerations. Fifty-eight percent of patients who sustained ruptured globes were left with no light perception in the affected eye. Average follow-up was 188 days. Average visual acuity significantly improved from logMAR 1.8±1.6 at presentation to logMAR 1.3±1.8 at last follow-up.ConclusionsFirework-related ocular trauma frequently results in vision-threatening pathology. Prompt referral to and treatment by ophthalmologists is critical. This study documents the dangers inherent in the personal use of fireworks and provides data that may help guide public policy to decrease the frequency of these devastating injuries.

Ocular injuries from fireworks: the 11-year experience of a US level I trauma center

PubMed Central

Chang, I T; Prendes, M A; Tarbet, K J; Amadi, A J; Chang, S-H; Shaftel, S S

2016-01-01

Purpose Characterize ocular trauma and visual outcomes from firework injuries at a level I trauma center. Methods Retrospective review of all firework injuries at Harborview Medical Center between 2003 and 2013. Results Three hundred and twenty-seven patients sustained firework injuries, of which 100 (31%) sustained ocular injuries. The average age of all patients who sustained fireworks injuries was 24.2 years, 89% were male and 54% of injuries occurred within 48 h of 4 July. Ocular injuries were most commonly caused by mortars (24%) and rockets (22%). Rockets were associated with four times the frequency of ocular injuries as compared with non-ocular injuries (P<0.001). Spectators were more likely to sustain ocular injuries than non-ocular injuries (P=0.001). The most common injuries sustained were corneal abrasions (67%), hyphemas (42%), eyelid injuries (39%), and ruptured globes (17%). Twenty-eight percent of patients with ocular injuries required surgical intervention. Ruptured globes occurred in 17% of patients, with the majority being complex corneoscleral lacerations. Fifty-eight percent of patients who sustained ruptured globes were left with no light perception in the affected eye. Average follow-up was 188 days. Average visual acuity significantly improved from logMAR 1.8±1.6 at presentation to logMAR 1.3±1.8 at last follow-up. Conclusions Firework-related ocular trauma frequently results in vision-threatening pathology. Prompt referral to and treatment by ophthalmologists is critical. This study documents the dangers inherent in the personal use of fireworks and provides data that may help guide public policy to decrease the frequency of these devastating injuries. PMID:27285323

Opacification of piggyback IOLs associated with an amorphous material attached to interlenticular surfaces.

PubMed

Werner, L; Shugar, J K; Apple, D J; Pandey, S K; Escobar-Gomez, M; Visessook, N; Evans, B B

2000-11-01

To report the pathological and ultrastructural features and interval surgical management of an atypical case of opacification between piggyback intraocular lenses (IOLs). Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, and Nature Coast EyeCare Institute and Surgery Center, Perry, Florida, USA. Opacification between 2 acrylic piggyback lenses was observed 16 months after implantation, with decreased best corrected visual acuity and a hyperopic shift. Elschnig pearls were observed in the peripheral interface between the lenses, and the central interface was occupied by an amorphous material. The pearls were surgically aspirated, but attempts to remove the central material were unsuccessful. The lenses were explanted and sent to the laboratory. Staining with hematoxylin and eosin (H&E), examination under a light microscope, and scanning electron microscopic analysis were performed. The surfaces of the anterior IOL were relatively clear. The amorphous material, mostly attached to the center of the anterior surface of the posterior IOL, was homogeneously stained with H&E. No cell nucleus was observed in this region. Scanning electron microscopy showed that the IOL edge presented a smooth, regular surface relatively free of deposits. The most central region was covered by an irregular layer of an amorphous compact material with some cracks, fissures, or both on its surface. Although the exact composition of the material between the lenses could not be established, hypotheses were advanced to understand the pathological mechanism associated with this condition. This case is different from those in previous reports of opacification composed of cortex and cells between piggyback IOLs.

TRI Microspheres prevent key signs of dry eye disease in a murine, inflammatory model.

PubMed

Ratay, Michelle L; Balmert, Stephen C; Acharya, Abhinav P; Greene, Ashlee C; Meyyappan, Thiagarajan; Little, Steven R

2017-12-13

Dry eye disease (DED) is a highly prevalent, ocular disorder characterized by an abnormal tear film and ocular surface. Recent experimental data has suggested that the underlying pathology of DED involves inflammation of the lacrimal functional unit (LFU), comprising the cornea, conjunctiva, lacrimal gland and interconnecting innervation. This inflammation of the LFU ultimately results in tissue deterioration and the symptoms of DED. Moreover, an increase of pathogenic lymphocyte infiltration and the secretion of pro-inflammatory cytokines are involved in the propagation of DED-associated inflammation. Studies have demonstrated that the adoptive transfer of regulatory T cells (Tregs) can mediate the inflammation caused by pathogenic lymphocytes. Thus, as an approach to treating the inflammation associated with DED, we hypothesized that it was possible to enrich the body's own endogenous Tregs by locally delivering a specific combination of Treg inducing factors through degradable polymer microspheres (TRI microspheres; TGF-β1, Rapamycin (Rapa), and IL-2). This local controlled release system is capable of shifting the balance of Treg/T effectors and, in turn, preventing key signs of dry eye disease such as aqueous tear secretion, conjunctival goblet cells, epithelial corneal integrity, and reduce the pro-inflammatory cytokine milieu in the tissue.

Down-regulation of Pax6 is associated with abnormal differentiation of corneal epithelial cells in severe ocular surface diseases

PubMed Central

Li, W; Chen, Y-T; Hayashida, Y; Blanco, G; Kheirkah, A; He, H; Chen, S-Y; Liu, C-Y; Tseng, SCG

2010-01-01

Pax6 is the universal master control gene for eye morphogenesis. Other than retina and lens, Pax6 also expressed in the ocular surface epithelium from early gestation until the postnatal stage, in which little is known about the function of Pax6. In this study, corneal pannus tissues from patients with ocular surface diseases such as Stevens–Johnson syndrome (SJS), chemical burn, aniridia and recurrent pterygium were investigated. Our results showed that normal ocular surface epithelial cells expressed Pax6. However, corneal pannus epithelial cells from the above patients showed a decline or absence of Pax6 expression, accompanied by a decline or absence of K12 keratin but an increase of K10 keratin and filaggrin expression. Pannus basal epithelial cells maintained nuclear p63 expression and showed activated proliferation, evidenced by positive Ki67 and K16 keratin staining. On 3T3 fibroblast feeder layers, Pax6 immunostaining was negative in clones generated from epithelial cells harvested from corneal pannus from SJS or aniridia, but positive in those from the normal limbal epithelium; whereas western blots showed that some epithelial clones expanded from pannus retained Pax6 expression. Transient transfection of an adenoviral vector carrying EGFP–Pax6 transgenes into these Pax6− clones increased both Pax6 and K12 keratin expression. These results indicate that Pax6 helps to maintain the normal corneal epithelial phenotype postnatally, and that down-regulation of Pax6 is associated with abnormal epidermal differentiation in severe ocular surface diseases. Reintroduction of activation of the Pax6 gene might be useful in treating squamous metaplasia of the ocular surface epithelium. PMID:18027901

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

[Eye and the pregnacy].

PubMed

Dima, Anne Marie

2012-01-01

Pregnancy is associated with changes in many organs and systems including the eyes. Sometimes in pregnancy may appear physiological and pathological ocular changes that may be associated with pre-existing problems. In such cases it is very important interdisciplinary collaboration gynecologist, ophthalmologist.

[Rare ocular manifestation with suspect alport syndrome].

PubMed

Krejčířová, I; Varadyová, B; Doležel, Z; Autrata, R; Matúšová, J; Gregorová, E

2014-06-01

The authors mention a case report of a 13 year old girl with renal disease, who visited the outpatient Department of Pediatric Ophthalmology, University Hospital Brno with subjective complaints on decreased vision of both eyes. Ophthalmologic examination showed physiological foveolar reflex on fundus and very discrete changes of the retinal pigment epithelium in macula, the fundus periphery was without pathology. OCT images showed bilateral atrophy of central macula and changes at the level of the photoreceptors. The authors describe a rare ocular manifestation of macular atrophy with suspect Alport syndrome, which strengthened the suspicion of this disease. The authors also mention other possible ocular manifestations of Alport syndrome and compare the findings with the up to date international references. Key words: Alport syndrome, X heterozygot Alport syndrome, macular atrophy, lentikonus.

Space flight-associated neuro-ocular syndrome (SANS).

PubMed

Lee, Andrew G; Mader, Thomas H; Gibson, C Robert; Brunstetter, Tyson J; Tarver, William J

2018-03-12

Interesting novel and somewhat perplexing physiologic and pathologic neuro-ocular findings have been documented in astronauts during and after long duration space flight (LDSF). These findings collectively have been termed the "space flight-associated neuro-ocular syndrome" (SANS). The National Aeronautics and Space Administration (NASA) in the United States has meticulously and prospectively documented the clinical, ultrasound, optical coherence tomography imaging, and radiographic findings of SANS including unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts (i.e., cotton wool spots). NASA and collaborating researchers continue to study SANS in preparation for future manned missions to space, including continued trips to the ISS, a return to the moon, or perhaps new voyages to the asteroid belt, or the planet, Mars.

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}\

Ocular toxoplasmosis II: clinical features, pathology and management

PubMed Central

Butler, Nicholas J; Furtado, João M; Winthrop, Kevin L; Smith, Justine R

2014-01-01

The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis. PMID:22712598

Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis.

PubMed

Chen, Wei; Zhang, Xiaobo; Liu, Mimi; Zhang, Jingna; Ye, Ya; Lin, Ying; Luyckx, Jacques; Qu, Jia

2009-09-01

The disaccharide trehalose is a key element involved in anhydrobiosis (the capability of surviving almost complete dehydration) in many organisms. Its presence also confers resistance to desiccation and high osmolarity in bacterial and human cells by protecting proteins and membranes from denaturation. The present study used a novel murine dry eye model induced by controlled low-humidity air velocity to determine whether topically applied trehalose could heal ocular surface epithelial disorders caused by ocular surface desiccation. In addition, the efficacy of 87.6 mM trehalose eyedrops was compared with that of 20% serum, the efficacy of which has been well documented. Mice ocular surface epithelial disorders were induced by exposure of murine eyes to continuous controlled low-humidity air velocity in an intelligently controlled environmental system (ICES) for 21 days, which accelerated the tear evaporation. The mice were then randomized into three groups: the control group received PBS (0.01 M) treatment; a second group received 87.6 mM trehalose eyedrops treatment; and the third group received mice serum eyedrops treatment. Each treatment was administered as a 10 microl dose every 6 h for 14 days. The resultant changes in corneal barrier function and histopathologic examination of cornea and conjunctiva were analyzed and the level of apoptosis on the ocular surface was assessed using active caspase-3. After 14 days of treatment, the corneal fluorescein staining area, the ruffling and desquamating cells on the apical corneal epithelium, as well as the apoptotic cells on ocular surface epithelium had significantly reduced in eyes treated with trehalose compared with those treated with serum and PBS. In contrast, after 14 days of treatment, improvements in the thickness of the corneal epithelium, the squamous metaplasia in conjunctival epithelium and the number of goblet cells of the conjunctiva were less marked in eyes treated with trehalose compared with serum. These results demonstrated that trehalose could improve the appearance of ocular surface epithelial disorders due to desiccation through suppression of apoptosis. Trehalose produces some of the same responses as serum upon topical application and can maintain corneal health.

Antioxidant delivery pathways in the anterior eye.

PubMed

Umapathy, Ankita; Donaldson, Paul; Lim, Julie

2013-01-01

Tissues in the anterior segment of the eye are particular vulnerable to oxidative stress. To minimise oxidative stress, ocular tissues utilise a range of antioxidant defence systems which include nonenzymatic and enzymatic antioxidants in combination with repair and chaperone systems. However, as we age our antioxidant defence systems are overwhelmed resulting in increased oxidative stress and damage to tissues of the eye and the onset of various ocular pathologies such as corneal opacities, lens cataracts, and glaucoma. While it is well established that nonenzymatic antioxidants such as ascorbic acid and glutathione are important in protecting ocular tissues from oxidative stress, less is known about the delivery mechanisms used to accumulate these endogenous antioxidants in the different tissues of the eye. This review aims to summarise what is currently known about the antioxidant transport pathways in the anterior eye and how a deeper understanding of these transport systems with respect to ocular physiology could be used to increase antioxidant levels and delay the onset of eye diseases.

Nanocarriers for treatment of ocular neovascularization in the back of the eye: new vehicles for ophthalmic drug delivery.

PubMed

Shen, Hsin-Hui; Chan, Elsa C; Lee, Jia Hui; Bee, Youn-Shen; Lin, Tsung-Wu; Dusting, Gregory J; Liu, Guei-Sheung

2015-01-01

Pathologic neovascularization of the retina is a major cause of substantial and irreversible loss of vision. Drugs are difficult to deliver to the lesions in the back of the eye and this is a major obstacle for the therapeutics. Current pharmacological approach involves an intravitreal injection of anti-VEGF agents to prevent aberrant growth of blood vessels, but it has limitations including therapeutic efficacy and side-effects associated with systemic exposure and invasive surgery. Nanotechnology provides novel opportunities to overcome the limitations of conventional delivery system to reach the back of the eye through fabrication of nanostructures capable of encapsulating and delivering small molecules. This review article introduces various forms of nanocarrier that can be adopted by ocular drug delivery systems to improve current therapy. The application of nanotechnology in medicine brings new hope for ocular drug delivery in the back of the eye to manage the major causes of blindness associated with ocular neovascularization.

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

Useful field of view test performance throughout adulthood in subjects without ocular disorders.

PubMed

Woutersen, Karlijn; van den Berg, Albert V; Boonstra, F Nienke; Theelen, Thomas; Goossens, Jeroen

2018-01-01

Previous research has shown an age-related decline in Useful Field of View (UFOV) test performance, which measures the duration required to extract relevant information from a scene in three subtasks. However, these results are mostly based on data that may have been confounded by (age-related) ocular diseases. We examined UFOV performance in subjects aged 19.5 to 70.3 years to investigate how UFOV performance changes throughout adulthood. All subjects underwent a thorough ophthalmological examination to exclude ocular disorders. We also examined some elementary visual functions, i.e., near and far visual acuity, crowding and contrast sensitivity. We investigated whether these functions were related to age and whether they could explain a possible age-related decline in UFOV performance. The subjects (n = 41) performed very well on almost every measure and reached far better UFOV and visual acuity scores than those reported by other studies that relied on self-reported absence of ocular pathology. We did not find significant relationships between age and any of the elementary visual functions or the first two UFOV subtasks (R2UFOV1 = 0.03, p = 0.25; R2UFOV2 = 0.07, p = 0.10). However, we found an age-related decline in performance on the third UFOV subtask (R2UFOV3 = 0.36, p < 0.001), which was unrelated to performance on the elementary visual function tasks. Our results show that performance on the first two UFOV subtasks as well as central elementary visual functions may remain high in the absence of obvious ophthalmological pathology.

Anti-VEGF aptamer (pegaptanib) therapy for ocular vascular diseases.

PubMed

Ng, Eugene W M; Adamis, Anthony P

2006-10-01

Vascular endothelial growth factor (VEGF) is a central regulator of both physiological and pathological angiogenesis. Pegaptanib, a 28-nucleotide RNA aptamer specific for the VEGF(165) isoform, binds to it in the extracellular space, leaving other isoforms unaffected, and inhibits such key VEGF actions as promotion of endothelial cell proliferation and survival, and vascular permeability. Pegaptanib already has been examined as a treatment for two diseases associated with ocular neovascularization, age-related macular degeneration (AMD) and diabetic macular edema (DME). Preclinical studies have shown that VEGF(165) alone mediates pathological ocular neovascularization and that its inactivation by pegaptanib inhibits the choroidal neovascularization observed in patients with neovascular AMD. In contrast, physiological vascularization, which is supported by the VEGF(121) isoform, is unaffected by this inactivation of VEGF(165). In addition, animal model studies have shown that intravitreous injection of pegaptanib can inhibit the breakdown of the blood-retinal barrier characteristic of diabetes and even can reverse this damage to some degree. These preclinical findings formed the basis for randomized controlled trials examining the efficacy of pegaptanib as a therapy for AMD and DME. The VEGF Inhibition Study in Ocular Neovascularization (VISION) trial comprising two replicate, pivotal phase 3 studies, demonstrated that intravitreous injection of pegaptanib resulted in significant clinical benefit, compared with sham injection, for all prespecified clinical end points, irrespective of patient demographics or angiographic subtype, and led to pegaptanib's approval as a treatment for AMD. A phase 2 trial has provided support for the efficacy of intravitreous pegaptanib in the treatment of DME.

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.

Prevalence, type, and prognosis of ocular lesions in shelter and owned-client dogs naturally infected by Leishmania infantum

PubMed Central

Pietro, Simona Di; Bosco, Valentina Rita Francesca; Crinò, Chiara; Francaviglia, Francesco; Giudice, Elisabetta

2016-01-01

Aim: The point prevalence of ocular lesions due to leishmaniasis was evaluated in 127 dogs living in a municipal shelter placed in a highly endemic area (Sicily, Italy). Moreover, the period prevalence, the type, and prognosis of lesions due to leishmaniasis were evaluated in 132 dogs with ocular pathologies referred to a Veterinary Teaching Hospital (VTH) in the same endemic area over a 3-year period. Materials and Methods: All the dogs were submitted to ophthalmological examination. The diagnosis of leishmaniasis was made by cytological, serological (immune-fluorescent antibody test), and molecular (quantitative polymerase chain reaction) tests. Results: The point prevalence of ocular lesions in 45 shelter dogs with leishmaniasis was 71.11% (45/127 dogs). The most frequent ocular lesion was blepharitis (50%) while anterior uveitis was observed in only 9.37% of cases. The period prevalence of ocular lesions due to leishmaniasis in the VTH group was 36.36% (48/132 dogs). In both groups, most of the lesions were bilateral and involved the anterior segment. Anterior uveitis was the most frequent ophthalmic finding in client-owned dogs (37.50%), but it occurred in only 9.37% of the shelter dogs. Keratouveitis often occurred during or after antiprotozoal treatment (14.58%; 7/48). In this study, the healing of eye injury following systemic antiprotozoal treatment was recorded in about half of cases (48%; 12/25 dogs), in which follow-up was possible. In more than 1/3 of cases (36%; 9/25), there was an improvement, but it was necessary to associate a long-term topical treatment; most of them, as well as those who had not responded to systemic therapy (16%; 4/25), had anterior uveitis or keratoconjunctivitis sicca. Conclusions: Ocular manifestations involve up to 2/3 of animals affected by canine leishmaniasis and lesions account for over 1/3 of ophthalmic pathologies observed at a referral clinic in an endemic area. The occurrence of anterior uveitis is more frequent in client-owned dogs than in shelter dogs. The onset of keratouveitis during or after antiprotozoal treatment could be attributed to the treatment or to a recurrence of the systemic form. The post-treatment uveal immune reaction, already observed in humans, could explain the difference in the frequency of keratouveitis between client-owned and shelter dogs, which have never been treated. PMID:27397988

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.

Accuracy of a technology-assisted eye exam in evaluation of referable diabetic retinopathy and concomitant ocular diseases.

PubMed

Conlin, Paul R; Asefzadeh, Baharak; Pasquale, Louis R; Selvin, Gerald; Lamkin, Rebecca; Cavallerano, Anthony A

2015-12-01

Digital retinal imaging using store-and-forward technology is used to screen for diabetic retinopathy (DR). Its usefulness in detecting non-diabetic eye diseases is uncertain. We determined the level of agreement between teleretinal imaging supplemented with visual acuity and intraocular pressure (IOP) measurements (ie, technology-assisted eye (TAE) exam) and a comprehensive eye exam in evaluation for DR and non-diabetic ocular conditions. We conducted a prospective, observational study with two parallel evaluations. Patients with diabetes (n=317) had a TAE exam and a comprehensive eye exam on the same day. A subset of participants with normal baseline exams (n=72) had follow-up exams 1 year later. We measured the level of agreement for referable ocular findings. Agreement for referable ocular findings was moderate (n=389, agreement: 77%; κ: 0.55), due in part to ungradable exams (22%). However, about half of the ungradable exams had findings that warranted referral. There was substantial agreement for follow-up exams (n=72, agreement: 93%; κ: 0.63). Among all gradable exams (n=303), the TAE exam had 86% sensitivity and 84% specificity for referable ocular findings, with high agreement (≥94%) for DR and other major ocular diagnoses. There was moderate-to-substantial agreement between a TAE exam and a comprehensive eye exam for referable ocular findings in patients with diabetes. Ungradable exams were a frequent marker of ocular pathology. Teleretinal imaging may be a useful evaluation for both diabetic and non-diabetic ocular conditions. 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-guided ocular growth in a mutant chicken model with diminished visual acuity

PubMed Central

Ritchey, Eric R.; Zelinka, Christopher; Tang, Junhua; Liu, Jun; Code, Kimberly A.; Petersen-Jones, Simon; Fischer, Andy J.

2012-01-01

Visual experience is known to guide ocular growth. We tested the hypothesis that vision-guided ocular growth is disrupted in a model system with diminished visual acuity. We examine whether ocular elongation is influenced by form-deprivation (FD) and lens-imposed defocus in the Retinopathy, Globe Enlarged (RGE) chicken. Young RGE chicks have poor visual acuity, without significant retinal pathology, resulting from a mutation in guanine nucleotide-binding protein β3 (GNB3), also known as transducin β3 or Gβ3. The mutation in GNB3 destabilizes the protein and causes a loss of Gβ3 from photoreceptors and ON-bipolar cells. (Ritchey et al. 2010)FD increased ocular elongation in RGE eyes in a manner similar to that seen in wild-type (WT) eyes. By comparison, the excessive ocular elongation that results from hyperopic defocus was increased, whereas myopic defocus failed to significantly decrease ocular elongation in RGE eyes. Brief daily periods of unrestricted vision interrupting FD prevented ocular elongation in RGE chicks in a manner similar to that seen in WT chicks. Glucagonergic amacrine cells differentially expressed the immediate early gene Egr1 in response to growth-guiding stimuli in RGE retinas, but the defocus-dependent up-regulation of Egr1 was lesser in RGE retinas compared to that of WT retinas. We conclude that high visual acuity, and the retinal signaling mediated by Gβ3, is not required for emmetropization and the excessive ocular elongation caused by FD and hyperopic defocus. However, the loss of acuity and Gβ3 from RGE retinas causes enhanced responses to hyperopic defocus and diminished responses to myopic defocus. PMID:22824538

Polarized light microscopy for 3-dimensional mapping of collagen fiber architecture in ocular tissues.

PubMed

Yang, Bin; Jan, Ning-Jiun; Brazile, Bryn; Voorhees, Andrew; Lathrop, Kira L; Sigal, Ian A

2018-04-06

Collagen fibers play a central role in normal eye mechanics and pathology. In ocular tissues, collagen fibers exhibit a complex 3-dimensional (3D) fiber orientation, with both in-plane (IP) and out-of-plane (OP) orientations. Imaging techniques traditionally applied to the study of ocular tissues only quantify IP fiber orientation, providing little information on OP fiber orientation. Accurate description of the complex 3D fiber microstructures of the eye requires quantifying full 3D fiber orientation. Herein, we present 3dPLM, a technique based on polarized light microscopy developed to quantify both IP and OP collagen fiber orientations of ocular tissues. The performance of 3dPLM was examined by simulation and experimental verification and validation. The experiments demonstrated an excellent agreement between extracted and true 3D fiber orientation. Both IP and OP fiber orientations can be extracted from the sclera and the cornea, providing previously unavailable quantitative 3D measures and insight into the tissue microarchitecture. Together, the results demonstrate that 3dPLM is a powerful imaging technique for the analysis of ocular tissues. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Safety study of intravitreal and suprachoroidal Laponite clay in rabbit eyes.

PubMed

Prieto, Esther; Vispe, Eugenio; De Martino, Alba; Idoipe, Miriam; Rodrigo, María J; Garcia-Martin, Elena; Fraile, José M; Polo-Llorens, Vicente; Mayoral, José A

2018-03-01

To study the safety and biocompatibility of Laponite clay (LAP) within an intravitreal and suprachoroidal administration in rabbit eyes. Thirty-two New Zealand albino rabbits were divided into two experimental groups to test intravitreal (IVT group) and suprachoroidal (SCS group) administration of a 100-μl and 50-μl Laponite suspension respectively. Following injection, the eyes were monitored by ocular tonometry, slit-lamp eye examination and indirect ophthalmoscopy, at 24 h, 1, 4, 12, and 14 weeks post administration. Histological examination was also performed to determine whether any ocular pathological change had occurred. Throughout the study, LAP presence in vitreous was estimated by complexometric titration with ethylenediaminetetraacetic acid (EDTA), taking advantage of the Laponite high content of magnesium ions. Neither significant differences in the intraocular pressure, nor relevant ocular complications were found in the two experimental groups after LAP administration. The histology of the retina remained unchanged. LAP presence in vitreous could be indirectly confirmed by complexometric titration until 14 weeks post administration in eyes of IVT group. Laponite could be considered as a vehicle for potential clinical use in ocular drug administration, due to its proven ocular biocompatibility and its transparency in gel state.

Ocular Angiogenesis: Vascular Endothelial Growth Factor and Other Factors.

PubMed

Rubio, Roman G; Adamis, Anthony P

2016-01-01

Systematic study of the mechanisms underlying pathological ocular neovascularization has yielded a wealth of knowledge about pro- and anti-angiogenic factors that modulate diseases such as neovascular age-related macular degeneration. The evidence implicating vascular endothelial growth factor (VEGF) in particular has led to the development of a number of approved anti-VEGF therapies. Additional proangiogenic targets that have emerged as potential mediators of ocular neovascularization include hypoxia-inducible factor-1, angiopoietin-2, platelet-derived growth factor-B and components of the alternative complement pathway. As for VEGF, knowledge of these factors has led to a product pipeline of many more novel agents that are in various stages of clinical development in the setting of ocular neovascularization. These agents are represented by a range of drug classes and, in addition to novel small- and large-molecule VEGF inhibitors, include gene therapies, small interfering RNA agents and tyrosine kinase inhibitors. In addition, combination therapy is beginning to emerge as a strategy to improve the efficacy of individual therapies. Thus, a variety of agents, whether administered alone or as adjunctive therapy with agents targeting VEGF, offer the promise of expanding the range of treatments for ocular neovascular diseases. © 2016 S. Karger AG, Basel.

Genome-Wide Identification of Chlamydia trachomatis Antigens Associated with Trachomatous Trichiasis

PubMed Central

Lu, Chunxue; Holland, Martin J.; Gong, Siqi; Peng, Bo; Bailey, Robin L.; Mabey, David W.; Wu, Yimou; Zhong, Guangming

2012-01-01

Purpose. Chlamydia trachomatis is the leading infectious cause of blindness. The goal of the current study was to search for biomarkers associated with C. trachomatis–induced ocular pathologies. Methods. We used a whole genome scale proteome array to systematically profile antigen specificities of antibody responses to C. trachomatis infection in individuals from trachoma-endemic communities with or without end-stage trachoma (trichiasis) in The Gambia. Results. When 61 trichiasis patients were compared with their control counterparts for overall antibody reactivity with organisms of different chlamydial species, no statistically significant difference was found. Both groups developed significantly higher titers of antibodies against C. trachomatis ocular serovars A and B than ocular serovar C, genital serovar D, or Chlamydia psittaci, whereas the titers of anti–Chlamydia pneumoniae antibodies were the highest. When antisera from 33 trichiasis and 26 control patients (with relatively high titers of antibodies to C. trachomatis ocular serovars) were reacted with 908 C. trachomatis proteins, 447 antigens were recognized by at least 1 of the 59 antisera, and 10 antigens by 50% or more antisera, the latter being designated as immunodominant antigens. More importantly, four antigens were preferentially recognized by the trichiasis group, with antigens CT414, CT667, and CT706 collectively reacting with 30% of trichiasis antisera but none from the normal group, and antigen CT695 reacting with 61% of trichiasis but only 31% of normal antisera. On the other hand, eight antigens were preferentially recognized by the control group, with antigens CT019, CT117, CT301, CT553, CT556, CT571, and CT709 together reacting with 46% of normal antisera and none from the trichiasis group, whereas antigen CT442 reacted with 35% of normal and 19% of trichiasis antisera respectively. Conclusions. The current study, by mapping immunodominant C. trachomatis antigens and identifying antigens associated with both ocular pathology and protection, has provided important information for further understanding chlamydial pathogenesis and the development of subunit vaccines. PMID:22427578

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

Lymphotoxin-beta receptor blockade reduces CXCL13 in lacrimal glands and improves corneal integrity in the NOD model of Sjögren's syndrome

PubMed Central

2011-01-01

Introduction In Sjögren's syndrome, keratoconjunctivitis sicca (dry eye) is associated with infiltration of lacrimal glands by leukocytes and consequent losses of tear-fluid production and the integrity of the ocular surface. We investigated the effect of blockade of the lymphotoxin-beta receptor (LTBR) pathway on lacrimal-gland pathology in the NOD mouse model of Sjögren's syndrome. Methods Male NOD mice were treated for up to ten weeks with an antagonist, LTBR-Ig, or control mouse antibody MOPC-21. Extra-orbital lacrimal glands were analyzed by immunohistochemistry for high endothelial venules (HEV), by Affymetrix gene-array analysis and real-time PCR for differential gene expression, and by ELISA for CXCL13 protein. Leukocytes from lacrimal glands were analyzed by flow-cytometry. Tear-fluid secretion-rates were measured and the integrity of the ocular surface was scored using slit-lamp microscopy and fluorescein isothiocyanate (FITC) staining. The chemokine CXCL13 was measured by ELISA in sera from Sjögren's syndrome patients (n = 27) and healthy controls (n = 30). Statistical analysis was by the two-tailed, unpaired T-test, or the Mann-Whitney-test for ocular integrity scores. Results LTBR blockade for eight weeks reduced B-cell accumulation (approximately 5-fold), eliminated HEV in lacrimal glands, and reduced the entry rate of lymphocytes into lacrimal glands. Affymetrix-chip analysis revealed numerous changes in mRNA expression due to LTBR blockade, including reduction of homeostatic chemokine expression. The reduction of CXCL13, CCL21, CCL19 mRNA and the HEV-associated gene GLYCAM-1 was confirmed by PCR analysis. CXCL13 protein increased with disease progression in lacrimal-gland homogenates, but after LTBR blockade for 8 weeks, CXCL13 was reduced approximately 6-fold to 8.4 pg/mg (+/- 2.7) from 51 pg/mg (+/-5.3) in lacrimal glands of 16 week old control mice. Mice given LTBR blockade exhibited an approximately two-fold greater tear-fluid secretion than control mice (P = 0.001), and had a significantly improved ocular surface integrity score (P = 0.005). The mean CXCL13 concentration in sera from Sjögren's patients (n = 27) was 170 pg/ml, compared to 92.0 pg/ml for sera from (n = 30) healthy controls (P = 0.01). Conclusions Blockade of LTBR pathways may have therapeutic potential for treatment of Sjögren's syndrome. PMID:22044682

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 prevalence and characteristics of chronic ocular itch: a cross-sectional survey.

PubMed

Stull, Carolyn; Valdes-Rodriguez, Rodrigo; Shafer, Brian M; Shevchenko, Alina; Nattkemper, Leigh A; Chan, Yiong-Huak; Tabaac, Sydney; Schardt, Martin J; Najjar, Dany M; Foster, William J; Yosipovitch, Gil

2017-03-01

In this cross-sectional study, we aimed to determine the prevalence and characteristics of chronic ocular itch in an outpatient ophthalmology and optometry clinic. Four hundred patients from an outpatient ophthalmology and optometry clinic were enrolled. The presence and characteristics of chronic ocular itch were assessed by a questionnaire. Data regarding ophthalmologic, dermatologic, and systemic conditions as well as current medications were extracted from medical records. Chronic ocular itch was present in 118 (29.5%) of 400 participants. Chronic ocular pruritus was significantly more prevalent in females [ P =0.015; odds ratio (OR)=1.8; 95% confidence interval (CI), 1.1-2.8] and was significantly associated with the presence of allergic conjunctivitis [51.8% (n=45); P <0.001; OR=5.0; 95% CI, 3.0-8.3], dry eye syndrome [40.1% (75); P <0.001; OR=2.6; 95% CI, 1.7-4.1], blepharitis [43.8% (n=21); P =0.021; OR=2.0; 95% CI, 1.1-3.8], and atopic dermatitis [50.0% (n=10); P =0.023; OR=2.6; 95% CI, 1.1-5.8]. Chronic ocular itch was not significantly associated with systemic conditions, or the use of prescribed ophthalmologic medications. Chronic ocular itch is common and may be related to ophthalmologic or dermatologic pathologies. The present findings highlight the importance of identifying and managing this uncomfortable symptom that may negatively impact the quality of life and sleep of affected patients.

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

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

The retina/RPE proteome in chick myopia and hyperopia models: Commonalities with inherited and age-related ocular pathologies

PubMed Central

Riddell, Nina; Faou, Pierre; Murphy, Melanie; Giummarra, Loretta; Downs, Rachael A.; Rajapaksha, Harinda

2017-01-01

Purpose Microarray and RNA sequencing studies in the chick model of early optically induced refractive error have implicated thousands of genes, many of which have also been linked to ocular pathologies in humans, including age-related macular degeneration (AMD), choroidal neovascularization, glaucoma, and cataract. These findings highlight the potential relevance of the chick model to understanding both refractive error development and the progression to secondary pathological complications. The present study aimed to determine whether proteomic responses to early optical defocus in the chick share similarities with these transcriptome-level changes, particularly in terms of dysregulation of pathology-related molecular processes. Methods Chicks were assigned to a lens condition (monocular +10 D [diopters] to induce hyperopia, −10 D to induce myopia, or no lens) on post-hatch day 5. Biometric measures were collected following a further 6 h and 48 h of rearing. The retina/RPE was then removed and prepared for liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) on an LTQ-Orbitrap Elite. Raw data were processed using MaxQuant, and differentially abundant proteins were identified using moderated t tests (fold change ≥1.5, Benjamini-Hochberg adjusted p<0.05). These differentially abundant proteins were compared with the genes and proteins implicated in previous exploratory transcriptome and proteomic studies of refractive error, as well as the genes and proteins linked to the ocular pathologies listed above for which myopia or hyperopia are risk factors. Finally, gene set enrichment analysis (GSEA) was used to assess whether gene sets from the Human Phenotype Ontology database were enriched in the lens groups relative to the no lens groups, and at the top or bottom of the protein data ranked by Spearman’s correlation with refraction at 6 and 48 h. Results Refractive errors of −2.63 D ± 0.31 D (mean ± standard error, SE) and 3.90 D ± 0.37 D were evident in the negative and positive lens groups, respectively, at 6 h. By 48 h, refractive compensation to both lens types was almost complete (negative lens −9.70 D ± 0.41 D, positive lens 7.70 D ± 0.44 D). More than 140 differentially abundant proteins were identified in each lens group relative to the no lens controls at both time points. No proteins were differentially abundant between the negative and positive lens groups at 6 h, and 13 were differentially abundant at 48 h. As there was substantial overlap in the proteins implicated across the six comparisons, a total of 390 differentially abundant proteins were identified. Sixty-five of these 390 proteins had previously been implicated in transcriptome studies of refractive error animal models, and 42 had previously been associated with AMD, choroidal neovascularization, glaucoma, and/or cataract in humans. The overlap of differentially abundant proteins with AMD-associated genes and proteins was statistically significant for all conditions (Benjamini-Hochberg adjusted p<0.05), with over-representation analysis implicating ontologies related to oxidative stress, cholesterol homeostasis, and melanin biosynthesis. GSEA identified significant enrichment of genes associated with abnormal electroretinogram, photophobia, and nyctalopia phenotypes in the proteins negatively correlated with ocular refraction across the lens groups at 6 h. The implicated proteins were primarily linked to photoreceptor dystrophies and mitochondrial disorders in humans. Conclusions Optical defocus in the chicks induces rapid changes in the abundance of many proteins in the retina/RPE that have previously been linked to inherited and age-related ocular pathologies in humans. Similar changes have been identified in a meta-analysis of chick refractive error transcriptome studies, highlighting the chick as a model for the study of optically induced stress with possible relevance to understanding the development of a range of pathological states in humans. PMID:29259393

Ocular toxoplasmosis II: clinical features, pathology and management.

PubMed

Butler, Nicholas J; Furtado, João M; Winthrop, Kevin L; Smith, Justine R

2013-01-01

The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

New clinical and experimental insights into Old World and neotropical ocular toxoplasmosis.

PubMed

Pfaff, Alexander W; de-la-Torre, Alejandra; Rochet, Elise; Brunet, Julie; Sabou, Marcela; Sauer, Arnaud; Bourcier, Tristan; Gomez-Marin, Jorge E; Candolfi, Ermanno

2014-02-01

Retinal lesions or other ocular manifestations are serious consequences of infection with the protozoan parasite Toxoplasma gondii. Whilst classically considered a consequence of congenital transmission, recent screening studies estimated that 2% of T. gondii seropositive persons in Europe and North America have retinal lesions, most of them persisting unnoticed. The situation is more dramatic in South America, probably due to the predominance of virulent strains. Some of these strains seem to exhibit ocular or neuronal tropism and are responsible for severe ocular lesions. Despite the medical importance, the physiopathological mechanisms have only recently begun to be elucidated. The particular immune-privileged situation in the eye has to be considered. Studies on French patients showed low or undetectable ocular parasite loads, but a clear Th1/Th17 type immune reaction. Suitable mouse models have appeared in the last few years. Using such a model, IL-17A proved to impair parasite control and induce pathology. In contrast, in South American patients, the parasite seems to be much less efficiently controlled through a Th2 type or suppressive immune response that favors parasite replication. Finally, several host genetic markers controlling immune response factors have been associated with ocular involvement of T. gondii infection, mainly in South America. Copyright © 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

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.

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.

Concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci.

PubMed

Mathes, Rachel L; Burdette, Erin L; Moore, Phillip A; Myrna, Kathern E

2012-03-01

To report concurrent clinical intraocular findings in horses with depigmented punctate chorioretinal foci and to document any correlation with equine recurrent uveitis (ERU). Records of 131 horses (241 eyes) examined at the University of Georgia Veterinary Teaching hospital from 2001 to 2010 were reviewed with either clinically normal fundi or depigmented punctate chorioretinal foci in the absence of other fundic pathology. Data collected included patient signalment, concurrent clinical ocular findings and follow-up information. Sex, presence of no other intraocular findings, presence of ERU, presence of cataracts, and presence of vitreal disease were compared between normal and foci groups using chi-squared analysis. Age and length of follow-up time were compared using a student's t-test. Ninety-one horses (167 eyes) with chorioretinal foci and forty horses (74 eyes) with clinically normal ocular fundi were examined. Fifty-eight (64%) horses with chorioretinal foci and 20 (50%) horses with clinically normal fundi had a normal intraocular examination. There was no significant difference in any of the criteria examined between groups. Horses with depigmented punctate chorioretinal foci, in the absence of other fundic pathology, are not more likely to have intraocular disease or ERU than horses with clinically normal ocular fundi. These findings suggest that depigmented punctate fundic foci in horses are not indicative of or associated with ERU. © 2011 American College of Veterinary Ophthalmologists.

Pathogenic role and therapeutic potential of pleiotrophin in mouse models of ocular vascular disease.

PubMed

Wang, Weiwen; LeBlanc, Michelle E; Chen, Xiuping; Chen, Ping; Ji, Yanli; Brewer, Megan; Tian, Hong; Spring, Samantha R; Webster, Keith A; Li, Wei

2017-11-01

Angiogenic factors play an important role in the pathogenesis of diabetic retinopathy (DR), neovascular age-related macular degeneration (nAMD) and retinopathy of prematurity (ROP). Pleiotrophin, a well-known angiogenic factor, was recently reported to be upregulated in the vitreous fluid of patients with proliferative DR (PDR). However, its pathogenic role and therapeutic potential in ocular vascular diseases have not been defined in vivo. Here using corneal pocket assays, we demonstrated that pleiotrophin induced angiogenesis in vivo. To investigate the pathological role of pleiotrophin we used neutralizing antibody to block its function in multiple in vivo models of ocular vascular diseases. In a mouse model of DR, intravitreal injection of pleiotrophin-neutralizing antibody alleviated diabetic retinal vascular leakage. In a mouse model of oxygen-induced retinopathy (OIR), which is a surrogate model of ROP and PDR, we demonstrated that intravitreal injection of anti-pleiotrophin antibody prevented OIR-induced pathological retinal neovascularization and aberrant vessel tufts. Finally, pleiotrophin-neutralizing antibody ameliorated laser-induced choroidal neovascularization, a mouse model of nAMD, suggesting that pleiotrophin is involved in choroidal vascular disease. These findings suggest that pleiotrophin plays an important role in the pathogenesis of DR with retinal vascular leakage, ROP with retinal neovascularization and nAMD with choroidal neovascularization. The results also support pleiotrophin as a promising target for anti-angiogenic therapy.

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.

Central Corneal Thickness and its Relationship to Intra-Ocular and Epidmiological Determinants.

PubMed

Tayyab, Ali; Masrur, Amena; Afzal, Farooq; Iqbal, Fyza; Naseem, Kamran

2016-06-01

To measure central corneal thickness in Pakistani population and determine its relationship to intra-ocular pressure, age, gender and ethnicity. Cross-sectional observation study. Pakistan Institute of Medical Sciences, Islamabad, Pakistan, between December 2013 and February 2015. The right eyes of 1000 cases (496 males and 504 females) were recruited for this study. Inclusion criteria were Pashtun or Punjabi ethnicity, intra-ocular pressure < 22 mmHg, gonioscopically open angles, cup-disk-ratio < 0.5, and age matched normal visual fields. Cases with prior ocular surgery, contact lens use, corneal pathologies, myopia or hypermetropia > ±3.0 diopters, astigmatism of > ±1.0 diopters were excluded. Central corneal thickness was measured using a TopCon non-contact specular microscope. Intra-ocular pressure was measured using Goldmann applanation tonometer. Frequency distribution, test of significance, and regression analysis was carried out using Statistical Package for Social Sciences version 20.0. Mean age was 47.31 ±11.78 years. Ethnic composition was 51.6% (n=516) Pashtun and 48.4% (n=484) Punjabi. The mean central corneal thickness was 503.96 (±12.47) µm, while the mean intra-ocular pressure was 15.61 (±2.68) mmHg. Regression analysis showed a significant association between central corneal thickness and intra-ocular pressure (p=0.00) and age (p=0.00). A±100 µchange in central corneal thickness was associated with change in IOPof ±3.30 mmHg, whereas central corneal thickness decreased by 0.12 µm per year. No significant association could be established between central corneal thickness and ethnicity (p=0.19). Central corneal thickness of the studied races was comparable to non-Caucasians which affects intra-ocular pressure measurements, and decreases with increasing age. No relationship was observed between central corneal thickness and ethnicity or gender.

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

Occlusion of retinal capillaries caused by glial cell proliferation in chronic ocular inflammation.

PubMed

Bianchi, E; Ripandelli, G; Feher, J; Plateroti, A M; Plateroti, R; Kovacs, I; Plateroti, P; Taurone, S; Artico, M

2015-01-01

The inner blood-retinal barrier is a gliovascular unit in which glial cells surround capillary endothelial cells and regulate retinal capillaries by paracrine interactions. During chronic ocular inflammation, microvascular complications can give rise to vascular proliferative lesions, which compromise visual acuity. This pathologic remodelling caused by proliferating Müller cells determines occlusion of retinal capillaries. The aim of the present study was to identify qualitative and quantitative alterations in the retinal capillaries in patients with post-traumatic chronic ocular inflammation or post-thrombotic vascular glaucoma. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in retinal inflammation. Our electron microscopy findings demonstrated that during chronic ocular inflammation, thickening of the basement membrane, loss of pericytes and endothelial cells and proliferation of Müller cells occur with irreversible occlusion of retinal capillaries. Angiogenesis takes place as part of a regenerative reaction that results in fibrosis. We believe that VEGF and pro-inflammatory cytokines may be potential therapeutic targets in the treatment of this disease although further studies are required to confirm these findings.

Evaluation of the norrie disease gene in a family with incontinentia pigmenti.

PubMed

Shastry, B S; Trese, M T

2000-01-01

Incontinentia pigmenti (IP) is an ectodermal multisystem disorder which can affect dental, ocular, cardiac and neurologic structures. The ocular changes of IP can have a very similar appearance to the retinal detachment of X-linked familial exudative vitreoretinopathy, which has been shown to be caused by the mutations in the Norrie disease gene. Therefore, it is of interest to determine whether similar mutations in the gene can account for the retinal pathology in patients with IP. To test our hypothesis, we have analyzed the entire Norrie disease gene for a family with IP, by single strand conformational polymorphism followed by DNA sequencing. The sequencing data revealed no disease-specific sequence alterations. These data suggest that ocular findings of IP are perhaps associated with different genes and there is no direct relationship between the genotype and phenotype. Copyright 2000 S. Karger AG, Basel

Revisiting the role of erythropoietin for treatment of ocular disorders

PubMed Central

Shirley Ding, S L; Leow, S N; Munisvaradass, R; Koh, E H; Bastion, M L C; Then, K Y; Kumar, S; Mok, P L

2016-01-01

Erythropoietin (EPO) is a glycoprotein hormone conventionally thought to be responsible only in producing red blood cells in our body. However, with the discovery of the presence of EPO and EPO receptors in the retinal layers, the EPO seems to have physiological roles in the eye. In this review, we revisit the role of EPO in the eye. We look into the biological role of EPO in the development of the eye and the physiologic roles that it has. Apart from that, we seek to understand the mechanisms and pathways of EPO that contributes to the therapeutic and pathological conditions of the various ocular disorders such as diabetic retinopathy, retinopathy of prematurity, glaucoma, age-related macular degeneration, optic neuritis, and retinal detachment. With these understandings, we discuss the clinical applications of EPO for treatment of ocular disorders, modes of administration, EPO formulations, current clinical trials, and its future directions. PMID:27285322

Bim expression in endothelial cells and pericytes is essential for regression of the fetal ocular vasculature.

PubMed

Wang, Shoujian; Zaitoun, Ismail S; Johnson, Ryan P; Jamali, Nasim; Gurel, Zafer; Wintheiser, Catherine M; Strasser, Andreas; Lindner, Volkhard; Sheibani, Nader; Sorenson, Christine M

2017-01-01

Apoptosis plays a central role in developmental and pathological angiogenesis and vessel regression. Bim is a pro-apoptotic Bcl-2 family member that plays a prominent role in both developmental and pathological ocular vessel regression, and neovascularization. Endothelial cells (EC) and pericytes (PC) each play unique roles during vascular development, maintenance and regression. We recently showed that germline deletion of Bim results in persistent hyaloid vasculature, increased retinal vascular density and prevents retinal vessel regression in response to hyperoxia. To determine whether retinal vascular regression is attributable to Bim expression in EC or PC we generated mice carrying a conditional Bim allele (BimFlox/Flox) and VE-cadherin-cre (BimEC mice) or Pdgfrb-cre (BimPC mice). BimEC and BimPC mice demonstrated attenuated hyaloid vessel regression and postnatal retinal vascular remodeling. We also observed decreased retinal vascular apoptosis and proliferation. Unlike global Bim -/- mice, mice conditionally lacking Bim in EC or PC underwent hyperoxia-mediated vessel obliteration and subsequent retinal neovascularization during oxygen-induced ischemic retinopathy similar to control littermates. Thus, understanding the cell autonomous role Bim plays in the retinal vascular homeostasis will give us new insight into how to modulate pathological retinal neovascularization and vessel regression to preserve vision.

Update on pathology of ocular parasitic disease

PubMed Central

Das, Dipankar; Ramachandra, Varsha; Islam, Saidul; Bhattacharjee, Harsha; Biswas, Jyotirmay; Koul, Akanksha; Deka, Panna; Deka, Apurba

2016-01-01

Parasites are a group of eukaryotic organisms that may be free-living or form a symbiotic or parasitic relationship with the hosts. Consisting of over 800,000 recognized species, parasites may be unicellular (Protozoa) or multicellular (helminths and arthropods). The association of parasites with human population started long before the emergence of civilization. Parasitic zoonotic diseases are prevalent worldwide including India. Appropriate epidemiological data are lacking on existing zoonotic parasitic diseases, and newer diseases are emerging in our scenario. Systemic diseases such as cysticercosis, paragonimiasis, hydatidosis, and toxoplasmosis are fairly common. Acquired Toxoplasma infections are rising in immune-deficient individuals. Amongst the ocular parasitic diseases, various protozoas such as Cystoidea, trematodes, tissue flagellates, sporozoas etc. affect humans in general and eyes in particular, in different parts of the world. These zoonoses seem to be a real health related problem globally. Recent intensification of research throughout the world has led to specialization in biological fields, creating a conducive situation for researchers interested in this subject. The basics of parasitology lie in morphology, pathology, and with recent updates in molecular parasitology, the scope has extended further. The current review is to address the recent update in ophthalmic parasites with special reference to pathology and give a glimpse of further research in this field. PMID:27958200

Update on pathology of ocular parasitic disease.

PubMed

Das, Dipankar; Ramachandra, Varsha; Islam, Saidul; Bhattacharjee, Harsha; Biswas, Jyotirmay; Koul, Akanksha; Deka, Panna; Deka, Apurba

2016-11-01

Parasites are a group of eukaryotic organisms that may be free-living or form a symbiotic or parasitic relationship with the hosts. Consisting of over 800,000 recognized species, parasites may be unicellular (Protozoa) or multicellular (helminths and arthropods). The association of parasites with human population started long before the emergence of civilization. Parasitic zoonotic diseases are prevalent worldwide including India. Appropriate epidemiological data are lacking on existing zoonotic parasitic diseases, and newer diseases are emerging in our scenario. Systemic diseases such as cysticercosis, paragonimiasis, hydatidosis, and toxoplasmosis are fairly common. Acquired Toxoplasma infections are rising in immune-deficient individuals. Amongst the ocular parasitic diseases, various protozoas such as Cystoidea, trematodes, tissue flagellates, sporozoas etc. affect humans in general and eyes in particular, in different parts of the world. These zoonoses seem to be a real health related problem globally. Recent intensification of research throughout the world has led to specialization in biological fields, creating a conducive situation for researchers interested in this subject. The basics of parasitology lie in morphology, pathology, and with recent updates in molecular parasitology, the scope has extended further. The current review is to address the recent update in ophthalmic parasites with special reference to pathology and give a glimpse of further research in this field.

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.

Advances in the treatment of ocular dryness associated with Sjögren׳s syndrome.

PubMed

Ciurtin, Coziana; Ostas, Anca; Cojocaru, Viorica M; Walsh, Stephen B; Isenberg, David A

2015-12-01

Sjögren´s syndrome (SS) is an autoimmune rheumatic disease that is characterised by decreased exocrine gland function and frequent ocular symptoms associated with eye dryness. Significantly, dry eyes can lead to corneal abrasions, infection, ulceration, chronic scarring and, in severe cases, perforation. The available conventional therapies have limited efficacy and there are no biologic therapies licensed for use in SS patients. A literature search of PubMed (MEDLINE) and EMBASE electronic data bases was performed covering the period from January 1994 to September 2014. Evidence was graded in categories I-IV and a treatment algorithm, comprising first line, second line and rescue therapies for ocular dryness associated with SS was proposed. It is based on the current evidence of efficacy of different therapies and explores their link with the pathogenesis of ocular dryness associated with SS. Recent developments in the understanding of the pathogenesis of SS provided evidence that the ocular dryness is associated with pathologic infiltration and dysfunction of the lacrimal glands and changes in the tear composition, together with abnormalities involving the neurosecreting circuits. There is good evidence for the efficacy of topical artificial tears, antiinflammatories and Cyclosporine, and oral Pilocarpine and Cevimeline in controlling the symptoms of ocular dryness associated with SS. Conventional DMARDs are not particularly effective in addressing the symptoms of ocular dryness associated with SS, despite being commonly prescribed for other SS manifestations. Emerging evidence suggests that B cell and co-stimulatory targeted therapy may play a role in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

Emerging toxicities in the treatment of non-small cell lung cancer: ocular disorders.

PubMed

Agustoni, Francesco; Platania, Marco; Vitali, Milena; Zilembo, Nicoletta; Haspinger, Eva; Sinno, Valentina; Gallucci, Rosaria; de Braud, Filippo; Garassino, Marina Chiara

2014-02-01

The treatment of advanced disease (stage IIIb and IV) of non-small cell lung cancer (NSCLC) is based on systemic treatment with platinum-based chemotherapy or biological compounds depending on the disease molecular profile. In the last few years, intensive investigational efforts in anticancer therapy have led to the registration of new active chemotherapeutic agents, combination regimens, and biological drugs, expanding choices for customizing individual treatment. However, the introduction of new drugs in the clinical setting has led to several new toxicities, creating some difficulties in daily management. Among these, ocular toxicity is generally overlooked as more common toxicities such as myelosuppression, stomatitis, diarrhea, vomiting, "hand-foot syndrome", and neurological alterations attract greater attention. Ophthalmic complications from cytotoxic chemotherapeutics are rare, transient, and of mild/moderate intensity but irreversible acute disorders are possible. The best way to prevent potential irreversible visual complications is an awareness of the potential for ocular toxicity because dose reductions or early drug cessation can prevent serious ocular complications in the majority of cases. However, given the novelty of many therapeutic agents and the complexity of ocular pathology, oncologists may be unfamiliar with these adverse effects of anticancer therapy. Although toxicities from chemotherapy are generally intense but short lasting, toxicities related to targeted drugs are often milder but longer lasting and can persist throughout treatment. Here we review the principal clinical presentations of ocular toxicity arising from chemotherapy [1-3], target therapies [4], and newly developed drugs and provide some recommendations for monitoring and management of ocular toxicity. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Role of radiation therapy in the management of ocular reticulum cell sarcoma. [Efficacy and complications

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

Margolis, L.; Fraser, R.; Lichter, A.

Nine patients with ocular lymphomas were seen in the Department of Ophthalmology and the Division of Radiation Oncology at UCSF and Ralph K. Davies Medical Center, San Francisco, from 1968 through 1974. Six of the 9 patients had visual symptoms as the first manifestation of their disease. Eight of the 9 patients developed intracranial lymphoma at some time during the course of the disease. Despite lymphoma work-up including bone marrow biopsies and lymphangiogram, only 1 patient was found to have documented systemic involvement. The diagnosis of ocular lymphoma was based on pathologic material from the eye in 5 cases ormore » from central nervous system biopsy in 4 patients in association with tumor cell infiltrates in the retina and vitreous clouding. Radiation therapy to the eyes improved vision in 10 of 13 eyes treated in 8 patients. The usual dose was in the range of 3500 to 4500 rads given over 4 to 5 weeks. In addition, 7 patients received central nervous system irradiation. Review of the literature reinforced the findings of this series showing the frequent association of ocular lymphoma with intracranial lymphoma and the rare systemic dissemination. This disease process has previously been referred to as ocular reticulum cell sarcoma.« less

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

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.

Complete 360° circumferential gonioscopic optical coherence tomography imaging of the iridocorneal angle

PubMed Central

McNabb, Ryan P.; Challa, Pratap; Kuo, Anthony N.; Izatt, Joseph A.

2015-01-01

Clinically, gonioscopy is used to provide en face views of the ocular angle. The angle has been imaged with optical coherence tomography (OCT) through the corneoscleral limbus but is currently unable to image the angle from within the ocular anterior chamber. We developed a novel gonioscopic OCT system that images the angle circumferentially from inside the eye through a custom, radially symmetric, gonioscopic contact lens. We present, to our knowledge, the first 360° circumferential volumes (two normal subjects, two subjects with pathology) of peripheral iris and iridocorneal angle structures obtained via an internal approach not typically available in the clinic. PMID:25909021

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.

Topographic analyses of shape of eyes with pathologic myopia by high-resolution three-dimensional magnetic resonance imaging.

PubMed

Moriyama, Muka; Ohno-Matsui, Kyoko; Hayashi, Kengo; Shimada, Noriaki; Yoshida, Takeshi; Tokoro, Takashi; Morita, Ikuo

2011-08-01

To analyze the topography of human eyes with pathologic myopia by high-resolution magnetic resonance imaging (MRI) with volume rendering of the acquired images. Observational case series. Eighty-six eyes of 44 patients with high myopia (refractive error ≥-8.00 diopters [D] or axial length >26.5 mm) were studied. Forty emmetropic eyes were examined as controls. The participants were examined with an MRI scanner (Signa HDxt 1.5T, GE Healthcare, Waukesha, WI), and T(2)-weighted cubes were obtained. Volume renderings of the images from high-resolution 3-dimensional (3D) data were done by computer workstation. The margins of globes were then identified semiautomatically by the signal intensity, and the tissues outside the globes were removed. The 3D topographic characteristic of the globes and the distribution of the 4 distinct shapes of globes according to the symmetry and the radius of curvature of the contour of the posterior segment: the barrel, cylindric, nasally distorted, and temporally distorted types. In 69.8% of the patients with bilateral high myopia, both eyes had the same ocular shape. The most protruded part of the globe existed along the central sagittal axis in 78.3% of eyes and was slightly inferior to the central axis in the remaining eyes. In 38 of 68 eyes (55.9%) with bilateral pathologic myopia, multiple protrusions were observed. The eyes with 2 protrusions were subdivided into those with nasal protrusions and those with temporal protrusions. The eyes with 3 protrusions were subdivided into nasal, temporal superior, and temporal inferior protrusions. The eyes with visual field defects that could not be explained by myopic fundus lesions significantly more frequently had a temporally distorted shape. Eyes with ≥2 protrusions had myopic chorioretinal atrophy significantly more frequently than eyes with ≤1 protrusion. Our results demonstrate that it is possible to obtain a complete topographic image of human eyes by high-resolution MRI with volume-rendering techniques. The results showed that there are different ocular shapes in eyes with pathologic myopia, and that the difference in the ocular shape is correlated with the development of vision-threatening conditions in eyes with pathologic myopia. The author(s) have no proprietary or commercial interest in any materials discussed in this article. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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.

Long-term outcomes after adjunctive topical 5-flurouracil or mitomycin C for the treatment of surgically excised, localized ocular surface squamous neoplasia.

PubMed

Bahrami, Bobak; Greenwell, Timothy; Muecke, James S

2014-01-01

To report rates of recurrence and complications of localized ocular surface squamous neoplasia treated with 5-fluorouracil or mitomycin C as adjunctive treatment to surgical excision. Long-term follow up of two prospective, non-comparative interventional case series. One hundred fifty-three eyes with histologically confirmed localized, non-invasive ocular surface squamous neoplasia. 89 eyes were treated with adjuvant 5-fluorouracil and 64 eyes were treated with adjuvant mitomycin C. Following surgical excision±cryotherapy patients received topical 5-fluorouracil 1% four times daily for two weeks or topical mitomycin C 0.04% four times daily for two to three 1-week cycles. Ocular surface squamous neoplasia recurrence, complications of therapy and compliance. Median follow up was 33.6 (range 12-84) months and 57.9 (range 12-160) months in 5-fluorouracil and mitomycin C groups, respectively. There was one recurrence in the 5-fluorouracil group and no recurrences in the mitomycin C group. Side-effects occurred in 69% of 5-fluorouracil patients and 41% of mitomycin C patients. Five patients (6%) required intervention for treatment-related side-effects in the 5-fluorouracil group versus 11 (17%) in the mitomycin C group. No vision-threatening complications were noted. Long-term recurrence of localised ocular surface squamous neoplasia is rare when topical 5-fluorouracil or mitomycin C are used as adjunctive treatment to surgical excision. While side-effects are common, the majority are transient and rarely limit compliance. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

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.

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.

Interaction of somatoform and vestibular disorders

PubMed Central

Best, C; Eckhardt‐Henn, A; Diener, G; Bense, S; Breuer, P; Dieterich, M

2006-01-01

Background The high coincidence of organic vestibular and somatoform vertigo syndromes has appeared to support pathogenic models showing a strong linkage between them. It was hypothesised that a persisting vestibular dysfunction causes the development of anxiety disorders. Objective To determine the relation between vestibular deficits and somatoform vertigo disorders in an interdisciplinary prospective study. Methods Participants were divided into eight diagnostic groups: healthy volunteers (n = 26) and patients with benign paroxysmal positioning vertigo (BPPV, n = 11), vestibular neuritis (n = 11), Menière's disease (n = 7), vestibular migraine (n = 15), anxiety (n = 23), depression (n = 12), or somatoform disorders (n = 22). Neuro‐otological diagnostic procedures included electro‐oculography with rotatory and caloric testing, orthoptic examination with measurements of subjective visual vertical (SVV) and ocular torsion, and a neurological examination. Psychosomatic diagnostic procedures comprised interviews and psychometric instruments. Results Patients with BPPV (35.3%) and with vestibular neuritis (52.2%) had pathological test values on caloric irrigation (p<0.001). Otolith dysfunction with pathological tilts of SVV and ocular torsion was found only in patients with vestibular neuritis (p<0.001). Patients with Menière's disease, vestibular migraine, and psychiatric disorders showed normal parameters for vestibular testing but pathological values for psychometric measures. There was no correlation between pathological neurological and pathological psychometric parameters. Conclusions High anxiety scores are not a result of vestibular deficits or dysfunction. Patients with Menière's disease and vestibular migraine but not vestibular deficits showed the highest psychiatric comorbidity. Thus the course of vertigo syndromes and the possibility of a pre‐existing psychopathological personality should be considered pathogenic factors in any linkage between organic and psychometric vertigo syndromes. PMID:16614028

Contributions of Interleukin‐33 and TSLP in a papain‐soaked contact lens‐induced mouse conjunctival inflammation model

PubMed Central

Sugita, Jobu; Asada, Yosuke; Ishida, Waka; Iwamoto, Satoshi; Sudo, Katsuko; Suto, Hajime; Matsunaga, Toru; Fukuda, Ken; Fukushima, Atsuki; Yokoi, Norihiko; Ohno, Tatsukuni; Azuma, Miyuki; Ebihara, Nobuyuki; Saito, Hirohisa; Kubo, Masato; Nakae, Susumu

2017-01-01

Abstract Introduction Pathological changes of severe chronic allergic conjunctivitis are driven not only via acquired immunity but also via innate immunity. Type 2 immune response‐initiating cytokines may play some roles as innate immunity‐dependent components of the ocular surface inflammation. To investigate the involvement of type 2 immune response‐initiating cytokines in innate immunity‐dependent, papain‐induced conjunctival inflammation model using IL‐25‐, IL‐33‐, and TSLP receptor (TSLPR)‐knockout (KO) mice with reference to basophils and ILC2. Methods Papain‐soaked contact lenses (papain‐CLs) were installed in the conjunctival sacs of C57BL/6‐IL‐25 KO, IL‐33 KO, TSLPR KO, Rag2 KO, Bas‐TRECK, and wild‐type mice and their eyes were sampled at day 5. The eosinophil and basophil infiltration in papain‐CL model was evaluated histologically and cytokine expression was examined. To clarify the roles of basophils and ILC2, basophil/ILC2‐depletion experiments were carried out. Results Papain‐induced conjunctival inflammation exhibited eosinophil infiltration and upregulation of Th2 cytokine expression. Reduction of eosinophil and basophil infiltration and attenuated Th2 cytokine expression were observed in the papain‐CL model using IL‐33 KO and TSLPR KO mice. Depletion of basophils or ILC2s in the conjunctivae of the papain‐CL model reduced eosinophil infiltration. Conclusions Innate immunity‐driven type 2 immune responses of the ocular surface are dependent on IL‐33, TSLP, basophils, and ILC2. These components may be possible therapeutic targets for refractory allergic keratoconjunctivitis. PMID:28730605

Genome-Wide Identification of Circular RNAs as a Novel Class of Putative Biomarkers for an Ocular Surface Disease.

PubMed

Li, Xiu-Miao; Ge, Hui-Min; Yao, Jin; Zhou, Yun-Fan; Yao, Mu-Di; Liu, Chang; Hu, Hai-Tao; Zhu, Yun-Xi; Shan, Kun; Yan, Biao; Jiang, Qin

2018-06-27

Pterygium is a common ocular surface disease with an unknown etiology and threatens vision as it invades into the cornea. Circular RNAs (circRNAs) are a novel class of RNA transcripts that participate in several physiological and pathological processes. However, the role of circRNAs in pathogenesis of pterygium remains largely unknown. Genome-wide circRNA expression profiling was performed to identify pterygium -related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was performed to predict the function of differentially expressed circRNAs in pterygium. MTT assays, Ki67 staining, Transwell assay, Hoechst 33342 staining, and Calcein-AM/PI staining were performed to determine the effect of circRNA silencing on pterygium fibroblast and epithelial cell function. Approximately 669 circRNAs were identified to be abnormally expressed in pterygium tissues. GO analysis demonstrated that the host genes of differentially expressed circRNAs were targeted to extracellular matrix organization (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis showed that dysregulated circRNAs-mediated regulatory networks were mostly enriched in focal adhesion signaling pathway. Notably, circ_0085020 (circ-LAPTM4B) was shown as a potential biomarker for pterygium. circ_0085020 (circ-LAPTM4B) silencing affected the viability, proliferation, migration, and apoptosis of pterygium fibroblast and epithelial cells in vitro. This study provides evidence that circRNAs are involved in the pathogenesis of pterygium and might constitute promising targets for the therapeutic intervention of pterygium. © 2018 The Author(s). Published by S. Karger AG, Basel.

Binocular misalignments elicited by altered gravity provide evidence for nonlinear central compensation

PubMed Central

Beaton, Kara H.; Huffman, W. Cary; Schubert, Michael C.

2015-01-01

Increased ocular positioning misalignments upon exposure to altered gravity levels (g-levels) have been strongly correlated with space motion sickness (SMS) severity, possibly due to underlying otolith asymmetries uncompensated in novel gravitational environments. We investigated vertical and torsional ocular positioning misalignments elicited by the 0 and 1.8 g g-levels of parabolic flight and used these data to develop a computational model to describe how such misalignments might arise. Ocular misalignments were inferred through two perceptual nulling tasks: Vertical Alignment Nulling (VAN) and Torsional Alignment Nulling (TAN). All test subjects exhibited significant differences in ocular misalignments in the novel g-levels, which we postulate to be the result of healthy individuals with 1 g-tuned central compensatory mechanisms unadapted to the parabolic flight environment. Furthermore, the magnitude and direction of ocular misalignments in hypo-g and hyper-g, in comparison to 1 g, were nonlinear and nonmonotonic. Previous linear models of central compensation do not predict this. Here we show that a single model of the form a + bgε, where a, b, and ε are the model parameters and g is the current g-level, accounts for both the vertical and torsional ocular misalignment data observed inflight. Furthering our understanding of oculomotor control is critical for the development of interventions that promote adaptation in spaceflight (e.g., countermeasures for novel g-level exposure) and terrestrial (e.g., rehabilitation protocols for vestibular pathology) environments. PMID:26082691

Galectins expressed differently in genetically susceptible C57BL/6 and resistant BALB/c mice during acute ocular Toxoplasma gondii infection.

PubMed

Chen, S-J; Zhang, Y-X; Huang, S-G; Lu, F-L

2017-07-01

Ocular toxoplasmosis (OT) caused by Toxoplasma gondii is a major cause of infectious uveitis, however little is known about its immunopathological mechanism. Susceptible C57BL/6 (B6) and resistant BALB/c mice were intravitreally infected with 500 tachyzoites of the RH strain of T. gondii. B6 mice showed more severe ocular pathology and higher parasite loads in the eyes. The levels of galectin (Gal)-9 and its receptors (Tim-3 and CD137), interferon (IFN)-γ, IL-6 and IL-10 were significantly higher in the eyes of B6 mice than those of BALB/c mice; however, the levels of IFN-α and -β were significantly decreased in the eyes and CLNs of B6 mice but significantly increased in BALB/c mice after infection. After blockage of galectin-receptor interactions by α-lactose, neither ocular immunopathology nor parasite loads were different from those of infected BALB/c mice without α-lactose treatment. Although the expressions of Gal-9/receptor were significantly increased in B6 mice and Gal-1 and -3 were upregulated in both strains of mice upon ocular T. gondii infection, blockage of galectins did not change the ocular pathogenesis of genetic resistant BALB/c mice. However, IFN-α and -β were differently expressed in B6 and BALB/c mice, suggesting that type I IFNs may play a protective role in experimental OT.

Xeroderma pigmentosum with bilateral ocular surface squamous neoplasia and review of the literature

PubMed Central

Kalamkar, Charudutt; Radke, Nishant; Mukherjee, Amrita; Radke, Snehal

2016-01-01

Xeroderma pigmentosum is a rare genetic disorder associated with various ocular malignancies. Here we report a single paediatric case of xeroderma pigmentosum with bilateral ocular surface squamous neoplasia (OSSN) presenting with diffuse lesion in one eye and a large mass in the other eye. Diffuse OSSN in one eye was treated with topical chemotherapy using mitomycin-C (0.04%) and the large OSSN in the other eye was treated with a combination of surgery and topical chemotherapy. Long-term follow-up and a multimodality treatment approach are necessary to identify and manage recurrences of OSSN in XP. PMID:27166000

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.

Xeroderma pigmentosum with bilateral ocular surface squamous neoplasia and review of the literature.

PubMed

Kalamkar, Charudutt; Radke, Nishant; Mukherjee, Amrita; Radke, Snehal

2016-05-10

Xeroderma pigmentosum is a rare genetic disorder associated with various ocular malignancies. Here we report a single paediatric case of xeroderma pigmentosum with bilateral ocular surface squamous neoplasia (OSSN) presenting with diffuse lesion in one eye and a large mass in the other eye. Diffuse OSSN in one eye was treated with topical chemotherapy using mitomycin-C (0.04%) and the large OSSN in the other eye was treated with a combination of surgery and topical chemotherapy. Long-term follow-up and a multimodality treatment approach are necessary to identify and manage recurrences of OSSN in XP. 2016 BMJ Publishing Group Ltd.

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.

[Nystagmus].

PubMed

Jutila, Topi; Hirvonen, Timo P

2013-01-01

Physiological nystagmus stabilizes gaze during head movements and pathological nystagmus reflects a disorder of the vestibulo-ocular reflex (VOR). Pathological nystagmus appears or strengthens usually during change in head position. Therefore, dizziness or nystagmus associated with head movements is not specific to benign paroxysmal positional vertigo unless it is verified in specific positional test. Peripheral nystagmus decelerates during visual fixation, accelerates when gaze is turned towards the fast phase, does not change direction, and is usually composed of several directional components unlike central nystagmus. The velocity and frequency of the slow phase of nystagmus can be measured with electronystagmography or video-oculography.

A very rare case of bloody tears with enigmatic epistaxis and haematuria.

PubMed

Ho, Jason Z S; de Silva, Julian; Olver, Jane

2011-03-01

Bloody tears are a rare symptom that can be caused by local or systemic pathology. We describe a very rare case of bloody tears that resulted from hyperthyroidism. A 15-year-old female patient presented with a 6-month history of bloody tears and epistaxis. Examination excluded local ocular and nasal pathology, including neoplasm and coagulopathy. Systemic investigations identified elevated thyroid function and following treatment her symptoms resolved. We discuss the mechanism by which hyperthyroidism may induce haemostatic dysfunction. We present the first case of bloody tears secondary to thyroid dysfunction.

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.

[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.

Severe Phenotype of Keratitis-Ichthyosis-Deafness Syndrome With Presumed Ocular Surface Squamous Neoplasia.

PubMed

Serrano-Ahumada, Ana Silvia; Cortes-González, Vianney; González-Huerta, Luz María; Cuevas, Sergio; Aguilar-Lozano, Luis; Villanueva-Mendoza, Cristina

2018-02-01

The aim of this study was to describe a case of severe keratitis-ichthyosis-deafness (KID) syndrome with ocular surface squamous neoplasia. The affected patient underwent complete ocular and systemic examinations. The molecular studies included polymerase chain reaction amplification and automated DNA sequencing of the complete gap junction beta-2 (GJB2) gene coding sequence. A 30-year-old man presented with generalized erythro-hyperkeratosis and deafness and complaints of decreased visual acuity, tearing, and photophobia. Ophthalmic examination showed corneal erosion, vascularization, and a gray gelatinous lesion partially covering the right cornea, suggestive of squamous neoplasia. The clinical features were characteristic of KID syndrome. This diagnosis was confirmed with a DNA analysis showing the pathogenic variant p.D50N in the GJB2 gene. Presumed squamous neoplasia was treated with topical interferon α2b. KID syndrome is a very rare disease that has been reported with an incremental incidence of squamous cell carcinoma of the mucous membranes and skin (12%-15%). Here, we presented a case of severe systemic KID syndrome with ocular surface squamous neoplasia.

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.

Potential of FTIR spectroscopy for analysis of tears for diagnosis purposes.

PubMed

Travo, Adrian; Paya, Clément; Déléris, Gérard; Colin, Joseph; Mortemousque, Bruno; Forfar, Isabelle

2014-04-01

It has been widely reported that the tear film, which is crucially important as a protective barrier of the eye, undergoes biochemical changes as a result of a wide range of ocular pathology. This tends to suggest the possibility of early detection of ocular diseases on the basis of biochemical analysis of tears. However, studies of tears by conventional methods of biomolecular and biochemical analysis are often limited by methodological difficulties. Moreover, such analysis could not be applied in the clinic, where structural and morphological analyses by, mainly, slit-lamp biomicroscopy remains the recommended method. In this study, we assessed, for the first time, the potential of FTIR spectroscopy combined with advanced chemometric processing of spectral data for analysis of raw tears for diagnosis purposes. We first optimized sampling and spectral acquisition (tears collection method, tear sample volume, and preservation of the samples) for accurate spectral measurement. On the basis of the results, we focused our study on the possibility of discriminating tears from normal individuals from those of patients with different ocular pathologies, and showed that the most discriminating spectral range is that corresponding to variations of CH2 and CH3 of lipid aliphatic chains. We also report more subtle discrimination of tears from patients with keratoconus and those from patients with non-specific inflammatory ocular diseases, on the basis of variations in spectral ranges attributed notably to lipid and carbohydrate vibrations. Finally, we also succeeded in distinguishing tears from patients with early-stage and late-stage keratoconus on the basis of spectral features attributed to protein structure. Therefore, this study strongly suggests that FTIR spectral analysis of tears could be developed as a valuable and cost-saving tool for biochemical-based detection of ocular diseases, potentially before the appearance of the first morphological signs of diseases. Combined with supervised modelling methods and with use of a spectral data base acquired for representative patients, such a spectral approach could be a useful addition to current methods of clinical analysis for improvement of patient care.

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.

Phototoxic effects of an operating microscope on the ocular surface and tear film.

PubMed

Hwang, Hyung Bin; Kim, Hyun Seung

2014-01-01

We evaluated light exposure-induced dry eye syndrome by investigating the phototoxic effects of an operating microscope on the ocular surface and tear film in rabbits. Sixty eyes of 30 rabbits were divided into 3 groups based on the intensity of light exposure received from an operating microscope: Control group, no exposure to light; group A, 40,000-lx intensity for 30 minutes; and group B, 100,000-lx intensity for 30 minutes. To evaluate the potential damage to the ocular surface and tear film, Schirmer tests, rose bengal staining, and conjunctival impression cytology were performed before the light exposure and at 1, 3, and 5 days afterward. In addition, the expression of interleukin 1-beta was analyzed in tear samples. The expression of mucin 5AC was evaluated using immunofluorescence staining, and periodic acid-Schiff staining was conducted on conjunctival tissues. Corneal and conjunctival tissues were observed by means of electron microscopy. Potential damage to the ocular surface and tear film was found in the light-exposed groups as evidenced by decreased aqueous tear production, devitalized corneal and conjunctival epithelial cells, squamous metaplasia of conjunctival epithelial cells, decreased conjunctival goblet cell density, decreased expression of mucin 5AC, ultrastructural cellular damage to corneal and conjunctival tissues, and increased interleukin 1-beta expression in tears. This damage was more noticeable in group B than in group A (P < 0.05). Light exposure from an operating microscope had phototoxic effects on the ocular surface and tear film in this in vivo experiment. These changes seemed to intensify as the intensity of the light increased. Therefore, excessive light exposure during ophthalmic procedures could be a pathogenic factor in dry eye syndrome after a surgery is performed.

The utilization of an ocular wound chamber on corneal epithelial wounds

PubMed Central

McDaniel, Jennifer S; Holt, Andrew W; Por, Elaine D; Eriksson, Elof; Johnson, Anthony J; Griffith, Gina L

2018-01-01

Purpose Currently available ocular moisture chambers are not adequate to manage the treatment of periocular burns, corneal injuries, and infection. The purpose of these studies was to demonstrate that a flexible, semi-transparent ocular wound chamber device adapted from technology currently used on dermal wounds is safe for use on corneal epithelial injuries. Materials and methods A depilatory cream (Nair™, 30 seconds) was utilized to remove the excess hair surrounding the left eyes of anesthetized Institute Armand Frappier (IAF) hairless, female guinea pigs (Crl:HA-Hrhr). A 4 mm corneal epithelium defect was created using a corneal rust ring remover (Algerbrush®II). Epithelial defects were either left untreated or the eyes were fitted with an ocular wound chamber and 0.5 mL of hydroxypropyl methylcellulose (HPMC) gel (GenTeal®) or HPMC liquid (GenTeal®) was injected into each chamber (N=5 per group). At 0, 24, 48, and 72 hours fluorescein and optical coherence tomography imaging was collected and the intraocular pressure (IOP) was measured. H&E staining was performed on corneal and eyelid skin samples and evaluated by a veterinary pathologist. Results Corneal epithelial wounds demonstrated 100% closure rates when left untreated or treated with an ocular wound chamber containing HPMC gel at 72 hours while wounds treated with an ocular wound chamber containing HPMC liquid were 98% healed. No significant differences were found in corneal thickness and wound healing, IOP, or eyelid skin pathology in any treatment group when compared to controls. Conclusions This study indicates that adapted wound chamber technology can be safely used on sterile, corneal epithelial wounds without adverse effects on periocular or ocular tissue when filled with a liquid or gel. PMID:29785086

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.

Canine viral infections.

PubMed

Willis, A M

2000-09-01

The ophthalmic effects of viral infection are varied. With the added possibility for pathologic effects of attenuated vaccine viruses, the diagnosis of viral diseases can be a challenge. In many cases, ocular manifestations can provide added support to a presumptive diagnosis of viral disease, thereby underscoring the benefit of thorough ophthalmic examination of any animal with nonspecific signs of illness.

Wavefront shaping to correct intraocular scattering

NASA Astrophysics Data System (ADS)

Artal, Pablo; Arias, Augusto; Fernández, Enrique

2018-02-01

Cataracts is a common ocular pathology that increases the amount of intraocular scattering. It degrades the quality of vision by both blur and contrast reduction of the retinal images. In this work, we propose a non-invasive method, based on wavefront shaping (WS), to minimize cataract effects. For the experimental demonstration of the method, a liquid crystal on silicon (LCoS) spatial light modulator was used for both reproduction and reduction of the realistic cataracts effects. The LCoS area was separated in two halves conjugated with the eye's pupil by a telescope with unitary magnification. Thus, while the phase maps that induced programmable amounts of intraocular scattering (related to cataract severity) were displayed in a one half of the LCoS, sequentially testing wavefronts were displayed in the second one. Results of the imaging improvements were visually evaluated by subjects with no known ocular pathology seeing through the instrument. The diffracted intensity of exit pupil is analyzed for the feedback of the implemented algorithms in search for the optimum wavefront. Numerical and experimental results of the imaging improvements are presented and discussed.

The retina as a window to the brain-from eye research to CNS disorders.

PubMed

London, Anat; Benhar, Inbal; Schwartz, Michal

2013-01-01

Philosophers defined the eye as a window to the soul long before scientists addressed this cliché to determine its scientific basis and clinical relevance. Anatomically and developmentally, the retina is known as an extension of the CNS; it consists of retinal ganglion cells, the axons of which form the optic nerve, whose fibres are, in effect, CNS axons. The eye has unique physical structures and a local array of surface molecules and cytokines, and is host to specialized immune responses similar to those in the brain and spinal cord. Several well-defined neurodegenerative conditions that affect the brain and spinal cord have manifestations in the eye, and ocular symptoms often precede conventional diagnosis of such CNS disorders. Furthermore, various eye-specific pathologies share characteristics of other CNS pathologies. In this Review, we summarize data that support examination of the eye as a noninvasive approach to the diagnosis of select CNS diseases, and the use of the eye as a valuable model to study the CNS. Translation of eye research to CNS disease, and deciphering the role of immune cells in these two systems, could improve our understanding and, potentially, the treatment of neurodegenerative disorders.

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.

Expression Analysis of the Transmembrane Mucin MUC20 in Human Corneal and Conjunctival Epithelia

PubMed Central

Woodward, Ashley M.; Argüeso, Pablo

2014-01-01

Purpose. Cell surface mucins are a group of highly O-glycosylated transmembrane glycoproteins responsible for the protection of epithelial cells on mucosal surfaces. The aim of this study was to investigate the localization and regulation of mucin 20 (MUC20) at the ocular surface. Methods. Localization of MUC20 in human corneal and conjunctival epithelia was evaluated by immunofluorescence microscopy. Immortalized corneal (HCLE) and conjunctival (HCjE) cell lines were grown at different stages of differentiation and subjected to quantitative PCR and Western blot analyses. Cell surface proteins on apical cell membranes were biotinylated and isolated by neutravidin chromatography. Results. The MUC20 was detected throughout the entire human ocular surface epithelia, predominantly in cell membranes within intermediate cell layers. In conjunctiva, MUC20 also was observed in the cytoplasm of apical cells within the stratified squamous epithelium, but not in goblet cells. Quantitative PCR and immunoblotting demonstrated expression of MUC20 in HCLE and HCjE cells. Induction of differentiation with serum-containing medium resulted in upregulation of MUC20 mRNA and protein. Biotin labeling of the surface of stratified cultures revealed low levels of MUC20 protein on apical glycocalyces. Further, MUC20 was not detected in the cell culture media or in human tears, suggesting that the extracellular domain of MUC20 is not released from the ocular surface as described previously for other cell surface mucins. Conclusions. Our results indicate that MUC20 is a novel transmembrane mucin expressed by the human corneal and conjunctival epithelia, and suggest that differential expression of MUC20 during differentiation has a role in maintaining ocular surface homeostasis. PMID:25168902

Integrated instrument for dynamic light scattering and natural fluorescence measurements

NASA Astrophysics Data System (ADS)

Rovati, Luigi; Pollonini, Luca; Ansari, Rafat R.

2001-06-01

Over the past two decades, great efforts have been made in ophthalmology to use optical techniques based on dynamic light scattering and tissue natural fluorescence for early (at molecular level) diagnosis of ocular pathologies. In our previous studies, the relationship between the corneal AF and DLS decay widths of ocular tissues were established by performing measurements on diabetes mellitus patients. In those studies, corneal AF mean intensities were significantly correlated with DLS decay width measurements for each diabetic retinopathy grade in the vitreous and in the cornea. This suggested that the quality of the diagnosis could be significantly improved by properly combining these two powerful techniques into a single instrument. Our approach is based on modifying a commercial scanning ocular fluorometer (Fluorotron Master, Ocumetrics Inc., CA, USA) to include both techniques in the same scanning unit. This configuration provides both DLS and AF real time measurements from the same ocular volume: they can be located in each section of the optical axis of the eye from the cornea to the retina. In this paper, the optical setup of the new system is described and preliminary in-vitro and in-vivo measurements are presented.

Viral infection of the lungs through the eye.

PubMed

Bitko, Vira; Musiyenko, Alla; Barik, Sailen

2007-01-01

Respiratory syncytial virus (RSV) is the foremost respiratory pathogen in newborns and claims millions of lives annually. However, there has been no methodical study of the pathway(s) of entry of RSV or its interaction with nonrespiratory tissues. We and others have recently established a significant association between allergic conjunctivitis and the presence of RSV in the eye. Here we adopt a BALB/c mouse model and demonstrate that when instilled in the live murine eye, RSV not only replicated robustly in the eye but also migrated to the lung and produced a respiratory disease that is indistinguishable from the standard, nasally acquired RSV disease. Ocularly applied synthetic anti-RSV small interfering RNA prevented infection of the eye as well as the lung. RSV infection of the eye activated a plethora of ocular cytokines and chemokines with profound relevance to inflammation of the eye. Anticytokine treatments in the eye reduced ocular inflammation but had no effect on viral growth in both eye and lung, demonstrating a role of the cytokine response in ocular pathology. These results establish the eye as a major gateway of respiratory infection and a respiratory virus as a bona fide eye pathogen, thus offering novel intervention and treatment options.

An unusual cause of post-operative orbital edema in a child after general anesthesia

PubMed Central

Tobias, Joseph D.; Jagannathan, Narasimhan; Sawardekar, Amod; Bhalla, Tarun

2011-01-01

We present an unusual ocular complication during the perioperative period, bilateral orbital edema in an otherwise healthy child after an outpatient surgical procedure. Ocular complications under general anesthesia remain a rare event. When periorbital edema is present, the appropriate work-up includes ruling out the potential for an allergic event by reviewing the medications administered and serum tryptase testing. Ophthalmology consultation should be considered to exclude pathology native to the eye itself. An allergist may assist in confirming a diagnosis and for allergic testing, if indicated. In our patient, the eventual diagnosis of exclusion was that of a localized reaction to the cellophane-based eye tape. PMID:21655032

An unusual cause of post-operative orbital edema in a child after general anesthesia.

PubMed

Tobias, Joseph D; Jagannathan, Narasimhan; Sawardekar, Amod; Bhalla, Tarun

2011-01-01

We present an unusual ocular complication during the perioperative period, bilateral orbital edema in an otherwise healthy child after an outpatient surgical procedure. Ocular complications under general anesthesia remain a rare event. When periorbital edema is present, the appropriate work-up includes ruling out the potential for an allergic event by reviewing the medications administered and serum tryptase testing. Ophthalmology consultation should be considered to exclude pathology native to the eye itself. An allergist may assist in confirming a diagnosis and for allergic testing, if indicated. In our patient, the eventual diagnosis of exclusion was that of a localized reaction to the cellophane-based eye tape.

Iris Positioning Using a Grid Attached to a Spring Bow for a Custom Ocular Prosthesis.

PubMed

Chamaria, Ankita; Aras, Meena Ajay; Chitre, Vidya; Costa, Godwin Clovis Da

2017-03-01

Eyes are among the first features of the face to be noticed. Loss of an eye due to congenital, traumatic or pathologic aetiologies causes disfigurement and loss of sensory feedback. It leaves a psychological impact on the patient, thus prosthesis should be provided at the earliest to raise the spirits of the afflicted. Iris positioning is one of the important steps in fabricating customized ocular prosthesis. In facial asymmetry cases, comparison of both irises together can be a major disadvantage. This case report illustrates the use of a unique customized frame spring bow assembly to position the iris disk using the established parallelism between inter pupillary line to the horizontal plane.

Severe ocular sequelae of congenital toxoplasmosis: huge macular scar.

PubMed

Zahir, Fadoua; Abdellaoui, Meriem; Younes, Samar; Benatiya, Idriss A; Tahri, Hicham

2015-01-01

Retinochoroiditis is the most common ocular manifestation of congenital toxoplasmosis, but other associated ophthalmological pathologies can also occur. Ophthalmologists are rarely able to distinguish between toxoplasmic retinochoroiditis due to infection acquired before or after birth, unless other clinical or serological indications are present. This article reports a case of a 3-year-old boy with abnormalities suggestive of congenital toxoplasmosis. The clinical and complementary examinations are discussed. The education of pregnant women is crucial for the prevention of congenital toxoplasmosis. Awareness of antenatal and postnatal presenting signs and symptoms is important for clinicians, because early diagnosis and treatment may minimize sequelae. Untreated, the majority of affected infants will develop chorioretinitis, deafness and/or neurological symptoms.

Efficiency of RAFT-synthesized PDMAEMA in gene transfer to the retina.

PubMed

Bitoque, Diogo B; Simão, Sónia; Oliveira, Ana V; Machado, Susana; Duran, Margarita R; Lopes, Eduardo; da Costa, Ana M Rosa; Silva, Gabriela A

2017-01-01

Gene therapy has long been heralded as the new hope to evolve from symptomatic care of genetic pathologies to a full cure. Recent successes in using gene therapy for treating several ocular and haematopoietic pathologies have shown the great potential of this approach that, in the early days, relied on the use of viral vectors, which were considered by many to be undesirable for human treatment. Therefore, there is considerable interest and effort in developing non-viral vectors, with efficiency close to that of viral vectors. The aim of this study was to develop suitable non-viral carriers for gene therapy to treat pathologies affecting the retina. In this study poly(2-(N,N-dimethylamino)ethyl methacrylate), PDMAEMA was synthesized by reversible addition-fragmentation chain transfer (RAFT) and the in vitro cytocompatibility and transfection efficiency of a range of polymer:DNA ratios evaluated using a retinal cell line; in vivo biocompatibility was evaluated by ocular injection in C57BL/6 mice. The results showed that through RAFT, it is possible to produce a defined-size polymer that is compatible with cell viability in vitro and capable of efficiently directing gene expression in a polymer-DNA ratio-dependent manner. When injected into the eyes of mice, these vectors induced a transient, mild inflammation, characteristic of the implantation of medical devices. These results form the basis of future studies where RAFT-synthesized PDMAEMA will be used to deliver gene expression systems to the retina of mouse models of retinal pathologies. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

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

Ocular firework injuries at New Year's eve.

PubMed

Sacu, Stefan; Ségur-Eltz, Nikolaus; Stenng, Karin; Zehetmayer, Martin

2002-01-01

To prospectively study mechanisms and injury characteristics of ocular firework burns. A prospective analysis of all patients with firework injuries attending the Department of Ophthalmology, University of Vienna, between 1994 and 2001. We looked for classes of fireworks and mechanisms of injuries. The number of diagnoses was established and their severity classified. During this period (8 years) we identified 116 eyes of 102 patients. 67/102 (66%) of all injuries were caused by class II and III fireworks. Patients ranged between 4 and 83 years. Ocular injuries occurred more frequently in males (69, 68%) and affected the right eye in 53 patients (52.5%). Ocular firework injuries to minors (under the age of 18 years) occurred in 48 (49%). The most common types of injury were skin and corneal erosions and abrasions (32/116, 28%). 11/116 eyes (10%) had severe injuries. 8 of 11 severe injuries (72%) occurred in minors (<18 years). 2 patients (1.7%) developed permanent blindness. In 32/116 patients (28%), the ocular trauma resulted in visual impairment, mainly due to corneal scars or retinal pathologies. In all patients, the severity index was 1.4 +/- 0.8. In minors the severity index was 1.6 +/- 1.0, in adults 1.2 +/- 0.5 (p = 0.013). Injuries in minors were significantly more severe than those in adults. Possible preventive measures include legislation, education of minors and eye protection. Copyright 2002 S. Karger AG, Basel

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.

The cellular mechanisms of dry eye: from pathogenesis to treatment.

PubMed

Mantelli, Flavio; Massaro-Giordano, Mina; Macchi, Ilaria; Lambiase, Alessandro; Bonini, Stefano

2013-12-01

Dry eye is a complex disease characterized by changes in the ocular surface epithelia related to reduced quality and/or quantity of tears, inflammatory reaction, and impairment of ocular surface sensitivity. It has recently been proposed that increased tear osmolarity represents a main trigger to the altered cellular mechanisms leading to epithelial damage in dry eye. However, dry eye pathogenesis is multifactorial, with cytotoxic inflammatory mediators, altered lacrimal gland secretion and nerve function, squamous metaplasia of the conjunctival epithelium and decrease of goblet cells density, all playing a role in a detrimental loop that perpetuates and worsens damage to the corneal and conjunctival epithelia. Current topical treatments for dry eye patients include the use of lubricants and anti-inflammatory drugs. However, lubricants only improve symptoms temporarily, and chronic use of topical steroids is associated to severe ocular side effects such as cataract and glaucoma. The deeper understanding of the cellular mechanisms that are altered in dry eye is opening novel perspectives for patients and physicians, who are seeking treatments capable not only of improving symptoms but also of restoring the homeostasis of the ocular surface. In this review, we will focus on novel anti-inflammatory agents and on nerve growth factor, a neurotrophin that is altered in dry eye and has been suggested as a main player in the neuroimmune cross-talk of the ocular surface as well as in the stimulation of corneal sensitivity, epithelial proliferation and differentiation, and stimulation of mucin production by goblet cells. J. Cell. Physiol. 228: 2253-2256, 2013. © 2013 Wiley Periodicals, Inc. Copyright © 2013 Wiley Periodicals, Inc.

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

[Effect of antenatal spiramycin treatment on the frequency of retinochoroiditis due to congenital toxoplasmosis in a Colombian cohort].

PubMed

Zuluaga, Liliana María; Hernández, John Camilo; Castaño, Carlos Felipe; Donado, Jorge Hernando

2017-04-01

Gestational toxoplasmosis is frequent and severe. There is still debate about the benefits of treatment against ocular manifestations in the newborn. Spiramycin treatment is used for this purpose, unfortunately prenatal diagnosis is sometimes delayed and pregnant women are not treated. To describe the relationship between treatment with spiramycin during pregnancy in mothers with gestational toxoplasmosis and development of ocular toxoplasmosis in newborns. We conducted a descriptive study of a case series. We evaluated a prospective cohort of patients diagnosed with gestational toxoplasmosis during three years at the Retinology Service at the Clínica Universitaria Bolivariana in Medellín. Gestational toxoplasmosis was found in 23 mothers; 15 (65%) were treated during pregnancy with 3 g per day of spiramycin, eight (35%) patients were untreated. In the treated group just one newborn developed ocular toxoplasmosis (6.6%), in contrast with five (62.5%) of the eight patients who did not receive treatment. These results suggest that pregnancy treatment reduces the relative risk of ocular toxoplasmosis in the newborn by 96% (95% CI: 33 - 100%). Only two (14%) of the patients who were evaluated, had nervous system involvement related to toxoplasmosis in CT scan or cerebral ultrasound. These two patients also developed ocular pathology and were diagnosed at the time of birth, so they did not received antenatal treatment. A protective effect was found against the ocular involvement in patients whose mother received treatment with spiramycin (OR=0.04;95% CI: 0.00-0.67), p<0.01 (Fisher's Exact Test).

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.

Surgical Reconstruction of Ocular Surface Tumors Using Fibrin Sealant Tissue Adhesive.

PubMed

Queiroz de Paiva, Aline Roseane; Abreu de Azevedo Fraga, Larissa; Torres, Virgínia Laura Lucas

2016-10-01

To evaluate the surgical outcomes of ocular surface reconstruction in corneal-conjunctival tumors using fibrin tissue adhesive. A prospective noncomparative study was performed between May 2013 and February 2015. Patients were submitted to routine surgical procedure for corneal-conjunctival tumor excision followed by amniotic membrane graft transplantation using fibrin tissue adhesive (Evicel®, Omrix Biopharmaceuticals Ltd., Israel). Results were assessed on the 1st, 7th, 15th and 30th postoperative days to analyze subjective complaints, adhesiveness and positioning of the graft, potential complications and recurrences. Twenty-five eyes were analyzed (male, 14). The diagnosis after the treatment was categorized as squamous cell neoplasia, dysplasia, actinic keratosis, squamous papilloma and compound melanocytic nevus. Few significant symptoms were reported, such as mild hyperemia and ocular dyscomfort. One case developed a conjunctival granuloma which regressed after topical treatment. All grafts were successful with no displacements or retraction postoperatively. There was no clinical recurrence of the tumor in a mean time of follow-up of 11 months. Fibrin tissue adhesive is safe and effective in the surgery of ocular surface tumor. In this series, sutureless amniotic membrane transplantation using fibrin glue has the potential to shorten the surgical time, mitigate inflammation postoperatively and improve patient discomfort.

James Wardrop and equine recurrent uveitis.

PubMed

Paglia, Danielle T; Miller, Paul E; Dubielzig, Richard R

2004-08-01

James Wardrop should be remembered not only as one of the founders of ocular pathology but also for his contributions to the field of comparative ophthalmology. He described a "specific inflammation" that veterinarians today know as equine recurrent uveitis. As described by Wardrop in the 19th century, this condition is known today to eventually lead to blindness.

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.

Keratoprostheses for corneal blindness: a review of contemporary devices

PubMed Central

Avadhanam, Venkata S; Smith, Helen E; Liu, Christopher

2015-01-01

According to the World Health Organization, globally 4.9 million are blind due to corneal pathology. Corneal transplantation is successful and curative of the blindness for a majority of these cases. However, it is less successful in a number of diseases that produce corneal neovascularization, dry ocular surface and recurrent inflammation, or infections. A keratoprosthesis or KPro is the only alternative to restore vision when corneal graft is a doomed failure. Although a number of KPros have been proposed, only two devices, Boston type-1 KPro and osteo-odonto-KPro, have came to the fore. The former is totally synthetic and the latter is semi-biological in constitution. These two KPros have different surgical techniques and indications. Keratoprosthetic surgery is complex and should only be undertaken in specialized centers, where expertise, multidisciplinary teams, and resources are available. In this article, we briefly discuss some of the prominent historical KPros and contemporary devices. PMID:25945031

Surgical outcome of deep anterior lamellar keratoplasty with air-assisted manual dissection for corneas with previous inflammation or fibrosis

PubMed Central

Ho, Yi-Ju; Wu, Cheng-Hsiu; Chen, Hung-Chi; Hsiao, Chin-Shi; Hsueh, Yi-Jen; Ma, David Hui-Kang

2017-01-01

PURPOSE: To report our experience in air-assisted manual dissection deep anterior lamellar keratoplasty (DALK) for the treatment of corneal scar with previous inflammation and fibrosis. MATERIALS AND METHODS: We retrospectively reviewed the medical history of 21 patients (male:female = 13:8 mean age 41.9 years old) with corneal pathology from previous infection and inflammation. Trephination diameter ranged from 7.0 to 8.0 mm, and the graft was oversized by 0.25–0.50 mm. Debulking technique was performed to expose Descemet's membrane after filling stroma with air. Starting from postoperative 3 months, selective suture removal was performed to reduce corneal astigmatism. RESULTS: The mean follow-up period was 59.9 ± 19.8 (20–96) months. Intraoperative microperforation occurred in 2 eyes (9.5%); however, there was no shift to penetrating keratoplasty. Air-bubble tamponade was performed in 7 eyes (33.3%) for postoperative gapping of the graft. There were 2 failed grafts (9.5%) due to corneal ulcer while all the other grafts remained clear throughout follow-up. The mean preoperative best-corrected visual acuity (BCVA) was 1.84 ± 0.66 logMAR, which improved to 0.74 ± 0.63 (P < 0.01). The average sphere power was − 0.88 ± 3.88 diopter (D), average cylinder power 3.03 ± 1.46D, and average endothelial count 1877 ± 375 cells/mm2. CONCLUSION: In severe ocular surface diseases, big-bubble technique frequently failed to separate predescemtic plane; however, it effectively created air-filled stroma which was easier to remove. Although BCVA was suboptimal due to ocular surface disorders, graft survival and clarity rate is high, justifying the application of DALK in these cases. PMID:29296551

Plasma rich in growth factors (PRGF) eye drops stimulates scarless regeneration compared to autologous serum in the ocular surface stromal fibroblasts.

PubMed

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

2015-06-01

Autologous serum (AS) eye drops was the first blood-derived product used for the treatment of corneal pathologies but nowadays PRGF arises as a novel interesting alternative to this type of diseases. The purpose of this study was to evaluate and compare the biological outcomes of autologous serum eye drops or Plasma rich in growth factors (PRGF) eye drops on corneal stromal keratocytes (HK) and conjunctival fibroblasts (HConF). To address this, blood from healthy donors was collected and processed to obtain autologous serum (AS) eye drops and plasma rich in growth factors (PRGF) eye drops. Blood-derivates were aliquoted and stored at -80°C until use. PDGF-AB, VEGF, EGF, FGFb and TGF-β1 were quantified. The potential of PRGF and AS in promoting wound healing was evaluated by means of proliferation and migration assays in HK and HConF. Fibroblast cells were induced to myofibroblast differentiation after treatment with 2.5ng/mL of TGF-β1. The capability of PRGF and AS to prevent and inhibit TGF-β1-induced differentiation was evaluated. Results showed significant higher levels of all growth factors analyzed in PRGF eye drops compared to AS. Moreover, PRGF eye drops enhanced significantly the biological outcomes of both HK and HConF, and reduced TGF-β1-induced myofibroblast differentiation in contrast to autologous serum eye drops (AS). In summary, these results suggest that PRGF exerts enhanced biological outcomes than AS. PRGF may improve the treatment of ocular surface wound healing minimizing the scar formation compared to AS. Results obtained herein suggest that PRGF protects and reverses the myofibroblast phenotype while promotes cell proliferation and migration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Establishment of an appropriate animal model for lacritin studies: cloning and characterization of lacritin in monkey eyes.

PubMed

Nakajima, T; Walkup, R D; Tochigi, A; Shearer, T R; Azuma, M

2007-11-01

Lacritin is a mitogen of human salivary gland cells as well as a stimulator of human corneal epithelial cells. It is expected to be an important factor in maintaining the surrounding ocular surface. The monkey would be a relevant animal model in which to study the role of lacritin in ophthalmic physiology and pathology. However, to our knowledge, no cDNA cloning or functional analysis of monkey lacritin has been performed. Thus, the purposes of this study were: (1) to clone the monkey ortholog of lacritin; (2) to characterize lacritin in tears from several species; and (3) to determine the tissues where lacritin is produced and secreted. cDNA for lacritin from rhesus macaque contained 547 bp, with 411 bp in an open reading frame (ORF) encoding a protein of 137 amino acids. Monkey lacritin showed 89% amino acid homology with human lacritin; one amino acid was deleted in all three monkey strains. The predicted MW of mature lacritin was 12.2 kDa, and the isoelectric point was 4.99. Lacritin showed anomalous migration at approximately 21.0 kDa on SDS-PAGE, as confirmed by immunoblotting and amino acid sequencing. Similar to native lacritin in monkey tears, a 21 kDa band was also detected in human tears. In contrast, no lacritin was observed at a similar position on SDS-PAGE in rat, rabbit and dog tears. In the monkey, lacritin mRNA was expressed highly in the lacrimal gland, moderately in the conjunctiva and the meibomian gland, and weakly in corneal epithelium. In primates, lacritin was produced in the lacrimal gland and secreted into tear fluid. These results suggest that lacritin might be important for the maintenance of the ocular surface in higher animals, such as monkeys and humans.

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.

Iris Positioning Using a Grid Attached to a Spring Bow for a Custom Ocular Prosthesis

PubMed Central

Aras, Meena Ajay; Chitre, Vidya; Costa, Godwin Clovis Da

2017-01-01

Eyes are among the first features of the face to be noticed. Loss of an eye due to congenital, traumatic or pathologic aetiologies causes disfigurement and loss of sensory feedback. It leaves a psychological impact on the patient, thus prosthesis should be provided at the earliest to raise the spirits of the afflicted. Iris positioning is one of the important steps in fabricating customized ocular prosthesis. In facial asymmetry cases, comparison of both irises together can be a major disadvantage. This case report illustrates the use of a unique customized frame spring bow assembly to position the iris disk using the established parallelism between inter pupillary line to the horizontal plane. PMID:28511522

Vitamin D: Implications for Ocular Disease and Therapeutic Potential

PubMed Central

Reins, Rose Y.; McDermott, Alison M.

2015-01-01

Vitamin D is a multifunctional hormone that is now known to play a significant role in a variety of biological functions in addition to its traditional role in regulating calcium homeostasis. There are a large number of studies demonstrating that adequate vitamin D levels are important in maintaining health and show that vitamin D is able to be utilized at local tissue sites. In the eye, we have increasing evidence of the association between disease and vitamin D. In this narrative review, we summarize recent findings on vitamin D and its relationship to various ocular pathologies and the therapeutic potential for some of these, as well as examine the basic science studies that demonstrate that vitamin D is biologically relevant in the eye. PMID:25724179

Protecting the retinal neurons from glaucoma: lowering ocular pressure is not enough.

PubMed

Pascale, Alessia; Drago, Filippo; Govoni, Stefano

2012-07-01

The retina is theater of a number of biochemical reactions allowing, within its layers, the conversion of light impulses into electrical signals. The axons of the last neuronal elements, the ganglion cells, form the optic nerve and transfer the signals to the brain. Therefore, an appropriate cellular communication, not only within the different retinal cells, but also between the retina itself and the other brain structures, is fundamental. One of the most diffuse pathologies affecting retinal function and communication, which thus reverberates in the whole visual system, is glaucoma. This insidious disease is characterized by a progressive optic nerve degeneration and sight loss which may finally lead to irreversible blindness. Nevertheless, the progressive nature of this pathology offers an opportunity for therapeutic intervention. To better understand the cellular processes implicated in the development of glaucoma useful to envision a targeted pharmacological strategy, this manuscript first examines the complex cellular and functional organization of the retina and subsequently identifies the targets sensitive to neurodegeneration. Within this context, high ocular pressure represents a key risk factor. However, recent literature findings highlight the concept that lowering ocular pressure is not enough to prevent/slow down glaucomatous damage, suggesting the importance of combining the hypotensive treatment with other pharmacological approaches, such as the use of neuroprotectants. Therefore, this important and more novel aspect is extensively considered in this review, also emphasizing the idea that the neuroprotective strategy should be extended to the entire visual system and not restricted to the retina. Copyright © 2012 Elsevier Ltd. All rights reserved.

A mouse model of ocular blast injury that induces closed globe anterior and posterior pole damage

PubMed Central

Hines-Beard, Jessica; Marchetta, Jeffrey; Gordon, Sarah; Chaum, Edward; Geisert, Eldon E.; Rex, Tonia S.

2012-01-01

We developed and characterized a mouse model of primary ocular blast injury. The device consists of: a pressurized air tank attached to a regulated paintball gun with a machined barrel; a chamber that protects the mouse from direct injury and recoil, while exposing the eye; and a secure platform that enables fine, controlled movement of the chamber in relation to the barrel. Expected pressures were calculated and the optimal pressure transducer, based on the predicted pressures, was positioned to measure output pressures at the location where the mouse eye would be placed. Mice were exposed to one of three blast pressures (23.6, 26.4, or 30.4psi). Gross pathology, intraocular pressure, optical coherence tomography, and visual acuity were assessed 0, 3, 7, 14, and 28 days after exposure. Contralateral eyes and non-blast exposed mice were used as controls. We detected increased damage with increased pressures and a shift in the damage profile over time. Gross pathology included corneal edema, corneal abrasions, and optic nerve avulsion. Retinal damage was detected by optical coherence tomography and a deficit in visual acuity was detected by optokinetics. Our findings are comparable to those identified in Veterans of the recent wars with closed eye injuries as a result of blast exposure. In summary, this is a relatively simple system that creates injuries with features similar to those seen in patients with ocular blast trauma. This is an important new model for testing the short-term and long-term spectrum of closed globe blast injuries and potential therapeutic interventions. PMID:22504073

The use of contact lenses in low vision rehabilitation: optical and therapeutic applications.

PubMed

Vincent, Stephen J

2017-09-01

Ocular pathology that manifests at an early age has the potential to alter the vision-dependent emmetropisation mechanism, which co-ordinates ocular growth throughout childhood. The disruption of this feedback mechanism in children with congenital or early-onset visual impairment often results in the development of significant ametropia, including high levels of spherical refractive error, astigmatism and anisometropia. This review examines the use of contact lenses as a refractive correction, low vision aid and therapeutic intervention in the rehabilitation of patients with bilateral, irreversible visual loss due to congenital ocular disease. The advantages and disadvantages of the use of contact lenses for increased magnification (telescopes and microscopes) or field expansion (reverse telescopes) are discussed, along with the benefits and practical considerations for the correction of pathological high myopia. The historical and present use of therapeutic tinted contact lenses to reduce photosensitivity and nystagmus in achromatopsia, albinism and aniridia are also presented, including clinical considerations for the contact lens practitioner. In addition to the known optical benefits in comparison to spectacles for high levels of ametropia (an improved field of view for myopes and fewer inherent oblique aberrations), contact lenses may be of significant psycho-social benefit for patients with low vision, due to enhanced cosmesis and reduced conspicuity and potential related effects of improved self-esteem and peer acceptance. The contact lens correction of patients with congenital vision impairment can be challenging for both practitioner and patient but should be considered as a potential optical or therapeutic solution in modern low vision rehabilitation. © 2017 Optometry Australia.

Identification of biomechanical properties of the cornea: the ocular response analyzer.

PubMed

Terai, Naim; Raiskup, Frederik; Haustein, Michael; Pillunat, Lutz E; Spoerl, Eberhard

2012-07-01

Several methods have been devised for measuring geometric parameters of the cornea but, until now, the biomechanics of the cornea have been largely ignored. The relatively new Ocular Response Analyzer (ORA) provides such biomechanical information. In order to correctly interpret the underlying biomechanics of ORA data, we review reported ORA measurements and provide a compendium of factors influencing these measurements, with discussion of possible explanations for ORA measurement results. This review comprised a literature search using "ocular response analyzer" and "ocular response analyser" as keywords. We reviewed and compared reported results from recent ORA studies so obtained, with an eye to understanding corneal biomechanics. Several ORA biomechanical parameters of the cornea - corneal hysteresis (CH) and corneal resistant factor (CRF) - characterize the viscoelastic properties of the cornea, especially those of the ground substance. The impact on CH and CRF values of various independent factors, e.g. intraocular pressure (IOP), age, central corneal thickness (CCT), and corneal swelling, are discussed. The impact on CH and CRF of treatment-related structural changes of the cornea, i.e. those occurring after refractive surgical procedures, placement of intracorneal rings, and collagen crosslinking (CXL), as well as pathological changes of the cornea, e.g. those resulting from keratoconus, edema, and glaucoma, are discussed. Changes in CRF and CH may be reflective of structural changes in the ground substance of the cornea. Thus, ORA provides invaluable information for delineating biomechanical conditions pertaining to the cornea, with special regard to ocular diseases, e.g. keratoconus and glaucoma.

Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases.

PubMed

Nguyen, Quan Dong; De Falco, Sandro; Behar-Cohen, Francine; Lam, Wai-Ching; Li, Xuri; Reichhart, Nadine; Ricci, Federico; Pluim, Jennifer; Li, William W

2018-02-01

The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research. © 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation and European Association for Vision & Eye Research.

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.

Value of subjective visual reduction in patients with acute-onset floaters and/or flashes.

PubMed

Hurst, Jonathan; Johnson, Davin; Law, Christine; Schweitzer, Kelly; Sharma, Sanjay

2015-08-01

To quantify the association between subjective visual reduction (SVR) and retinal pathology in patients with acute-onset monocular floaters or flashes, or both. Prospective cohorts study involving all new patients referred for acute-onset floaters or flashes, or both, to a tertiary care emergency eye clinic in Kingston, Ontario, between July 1, 2011, and June 29, 2012 (n = 333). All patients were evaluated for the presence of SVR in a standardized fashion, as well as other known risk factors for retina pathology including a family history of retinal tear or retinal detachment, a personal history of retinal tear or detachment, high myopia, and ocular trauma. Our major outcome was urgent retinal pathology, defined as retina pathology requiring a same-day referral to a retina specialist for evaluation, management, or both. SVR was strongly associated with retinal pathology (likelihood ratio 7.9, 95% CI 5.2-12.1). Patients with SVR are at increased risk for urgent retinal pathology and should be triaged for urgent ophthalmologic examination. Copyright © 2015 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Clinical predictors for the prognosis of myasthenia gravis.

PubMed

Wang, Lili; Zhang, Yun; He, Maolin

2017-04-19

Clinical predictors for myasthenia gravis relapse and ocular myasthenia gravis secondary generalization during the first two years after disease onset remain incompletely identified. This study attempts to investigate the clinical predictors for the prognosis of Myasthenia Gravis. Eighty three patients with myasthenia gravis were concluded in this study. Baseline characteristics were analyzed as predictors. Relapse of myasthenia gravis developed in 26 patients (34%). Generalization developed in 34 ocular myasthenia gravis patients (85%). Other autoimmune diseases were observed more commonly in relapsed myasthenia gravis (P = 0.012). Second generalization group contained more late onset patients (P = 0.021). Ocular myasthenia gravis patients with thymus hyperplasia progressed more rapidly than those with other thymus pathology (P = 0.027). Single onset symptom of ocular myasthenia gravis such as ptosis or diplopia predicted early progression than concurrence of ptosis and diplopia (P = 0.027). Treatment effect including glucocorticoid, pyridostigmine, thymectomy, IVIG, immunosuppressive drugs did not show significant difference between the relapsed and non-relapsed groups. The treatment outcome also showed no difference between the single OMG and second generalized groups. Occurrence of associated autoimmune disease can serve as a potential predictor for myasthenia gravis relapse. Either ptosis or diplopia, as well as thymic hyperplasia can predict generalization in the first six months.

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.

[Pediatric case series in an ophthalmic camp in Turkana (Kenya)].

PubMed

Noval, S; Cabrejas, L; Jarrín, E; Ruiz-Guerrero, M; Ciancas, E

2013-12-01

Turkana is the largest district in Kenya, situated in the Northwest of the country. It features a semi-nomadic population of 850,000. Around 60% of population lives below the poverty threshold. The ratio of doctors is 1:75,000 inhabitants. Five ophthalmologists took part in the last deployment in November. Local staff had previously selected the patients from the rural areas, as well as in Lodwar, the capital of the district. Of the 371 patients who attended the clinic, 128 required surgery. To describe the pediatric population attended to in the last «Turkana Eye Project» Camp. Description of the ophthalmic pathologies of the children seen in the clinic in this surgical camp, and the diagnostic and therapeutic options according to the limitations of the environment. Of the 371 patients, 54 were younger than 15 years old (14.5%). Four children had surgery (3.25% of the 128 patients). In 2 more cases surgery was the indicated but not performed. Therefore, of the total of 54 cases, 6 could be considered as surgical (11.1%), and 17 suffered ophthalmic problems other than refraction defects, or mild ocular surface pathologies: traumatic cataracts, neuropathies, impetigo, exophthalmos, retinal dystrophies, dermoid cysts, or nyctalopia. The etiology was traumatic in four of the 17 children (23.5%). Surgical camps are increasing in the developing countries. They are usually focused on particular pathologies, such as cataracts or trachoma. Our case series shows the importance of pediatric teams and the need to be prepared to face complex pediatric pathologies. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

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...

Pathogenesis of Acute and Delayed Corneal Lesions after Ocular Exposure to Sulfur Mustard Vapor

DTIC Science & Technology

2012-01-01

mechanistic understanding and therapeutic development. Here we evaluate the histopathologic, biochemical and ultrastructural expressions of...were identified, including destabilization of the basal corneal epithelium , basement membrane zone abnormalities and stromal deformation. Clinical...pathology of MGK, in part resulting from persistent necrosis of the basal corneal epithelium and deterioration of the basement membrane. The findings

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

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

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.

[Corneal manifestations in systemic diseases].

PubMed

Zarranz Ventura, J; De Nova, E; Moreno-Montañés, J

2008-01-01

Systemic diseases affecting the cornea have a wide range of manifestations. The detailed study of all pathologies that cause corneal alteration is unapproachable, so we have centered our interest in the most prevalent or characteristic of them. In this paper we have divided these pathologies in sections to facilitate their study. Pulmonar and conective tissue (like colagen, rheumatologic and idiopathic inflamatory diseases), dermatologic, cardiovascular, hematologic, digestive and hepatopancreatic diseases with corneal alteration are described. Endocrine and metabolic diseases, malnutrition and carential states are also studied, as well as some otorhinolaryngologic and genetic diseases that affect the cornea. Finally, a brief report of ocular toxicity induced by drugs is referred.

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

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.

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.

Delivery of therapeutics for deep-seated ocular conditions - status quo.

PubMed

Nguyen, Hubert; Eng, Shawn; Ngo, Thanh; Dass, Crispin R

2018-04-19

There is a need for research into designing effective pharmaceutical systems for delivering therapeutic drugs to the posterior of the eye for glaucoma-related pathology, macular degeneration, diabetic retinopathy, macular oedema, retinitis and choroiditis. Conventionally, eye drops have been extensively utilised for topical drug delivery to the anterior segment of the eye, but are less effective for delivery of therapeutics to the back of the eye due to significant barriers hampering drug penetration into the target intraocular tissue. This review explores some of the current and novel delivery systems employed to deliver therapeutics to the back of the eye such as those using liposomes, ocular implants, in situ gels, and nanoparticles, and how they can overcome some of these limitations. Issues such as blinking, precorneal fluid drainage, tear dilution and turnover, conjunctiva and nasal drug absorption, the corneal epithelium, vitreous drug clearance, and the blood-ocular barriers are reviewed and discussed. Further studies are needed to address their shortcomings such as drug compatibility and stability, economic viability and patient compliance. © 2018 Royal Pharmaceutical Society.

Trachoma and Ocular Chlamydial Infection in the Era of Genomics

PubMed Central

Derrick, Tamsyn; Roberts, Chrissy h.; Last, Anna R.; Burr, Sarah E.; Holland, Martin J.

2015-01-01

Trachoma is a blinding disease usually caused by infection with Chlamydia trachomatis (Ct) serovars A, B, and C in the upper tarsal conjunctiva. Individuals in endemic regions are repeatedly infected with Ct throughout childhood. A proportion of individuals experience prolonged or severe inflammatory episodes that are known to be significant risk factors for ocular scarring in later life. Continued scarring often leads to trichiasis and in-turning of the eyelashes, which causes pain and can eventually cause blindness. The mechanisms driving the chronic immunopathology in the conjunctiva, which largely progresses in the absence of detectable Ct infection in adults, are likely to be multifactorial. Socioeconomic status, education, and behavior have been identified as contributing to the risk of scarring and inflammation. We focus on the contribution of host and pathogen genetic variation, bacterial ecology of the conjunctiva, and host epigenetic imprinting including small RNA regulation by both host and pathogen in the development of ocular pathology. Each of these factors or processes contributes to pathogenic outcomes in other inflammatory diseases and we outline their potential role in trachoma. PMID:26424969

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

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.

Severe myopia with unusual retinal anomalies and Dandy-Walker sequence in two sibs. A distinct new neuro-ocular disorder.

PubMed

de Crecchio, Giuseppe; Cennamo, Gilda; de Leeuw, Nicole; Ventruto, Maria Luisa; Lonardo, Maria Concetta; Friso, Patrizia; Ventruto, Valerio

2013-12-01

We have observed a male and a female, sibs of non-consanguineous parents, affected by severe myopia with characteristic retinal defects and Dandy-Walker variant. The peculiarity of the retinopathy consists of pathological myopia with anomalous vitreal fenestrated membranes in the retinal periphery. We suppose that these associations may configure a new genetic syndrome.

High-resolution 3D MR microangiography of the rat ocular circulation.

PubMed

Shih, Yen-Yu I; Muir, Eric R; Li, Guang; De La Garza, Bryan H; Duong, Timothy Q

2012-07-01

To develop high-spatial-resolution magnetic resonance (MR) microangiography techniques to image the rat ocular circulation. Animal experiments were performed with institutional Animal Care Committee approval. MR microangiography (resolution, 84×84×84 μm or 42×42×84 μm) of the rat eye (eight rats) was performed by using a custom-made small circular surface coil with an 11.7-T MR unit before and after monocrystalline iron oxide nanoparticle (MION) injection. MR microangiography measurements were made during air, oxygen, and carbogen inhalation. From three-dimensional MR microangiography, the retina was virtually flattened to enable en face views of various retinal depths, including the retinal and choroidal vascular layers. Signal intensity changes within the retinal or choroidal arteries and veins associated with gas challenges were analyzed. Statistical analysis was performed by using paired t tests, with P<.05 considered to indicate a significant difference. Bonferroni correction was used to adjust for multiple comparisons. The central retinal artery, long posterior ciliary arteries, and choroidal vasculature could be distinguished on MR microangiograms of the eye. With MR microangiography, retinal arteries and veins could be distinguished on the basis of blood oxygen level-dependent contrast. Carbogen inhalation-enhanced MR microangiography signal intensity in both the retina (P=.001) and choroid (P=.027) compared with oxygen inhalation. Carbogen inhalation showed significantly higher signal intensity changes in the retinal arteries (P=.001, compared with oxygen inhalation), but not in the veins (P=.549). With MION administration, MR microangiography depicted retinal arterial vasoconstriction when the animals were breathing oxygen (P=.02, compared with animals breathing air). MR microangiography of the eye allows depth-resolved imaging of small angiographic details of the ocular circulation. This approach may prove useful in studying microvascular pathologic findings and neurovascular dysfunction in the eye and retina. © RSNA, 2012.

Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility

PubMed Central

Eidet, Jon R.; Utheim, Tor P.; Ræder, Sten; Lagali, Neil S.; Messelt, Edvard B.; Dartt, Darlene A.

2016-01-01

The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sjögren’s syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52% women and 48% men) with DED were included. Patient demographics were: 0 to 19 years (1%), 20 to 39 (25%), 40 to 59 (34%), 60 to 79 (35%) and 80 to 99 (5%). Xerostomia, defined as “daily symptoms of dry mouth the last three months” (as presented in SSQ) was reported by 23% of the patients. Female sex was more common among patients with xerostomia (81%) than among non-xerostomia patients (44%; P<0.001). Patients with xerostomia (60 ± 15 years) were older than those without xerostomia (51 ± 17; P<0.001). The use of prescription drugs was more prevalent among xerostomia patients (65%) than among non-xerostomia patients (35%; P<0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 ± 10.0) than those without xerostomia (12.9 ± 8.0; P<0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 ± 0.7) than those without xerostomia (0.7 ± 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients. PMID:27148875

Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility.

PubMed

Fostad, Ida G; Eidet, Jon R; Utheim, Tor P; Ræder, Sten; Lagali, Neil S; Messelt, Edvard B; Dartt, Darlene A

2016-01-01

The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sjögren's syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52% women and 48% men) with DED were included. Patient demographics were: 0 to 19 years (1%), 20 to 39 (25%), 40 to 59 (34%), 60 to 79 (35%) and 80 to 99 (5%). Xerostomia, defined as "daily symptoms of dry mouth the last three months" (as presented in SSQ) was reported by 23% of the patients. Female sex was more common among patients with xerostomia (81%) than among non-xerostomia patients (44%; P<0.001). Patients with xerostomia (60 ± 15 years) were older than those without xerostomia (51 ± 17; P<0.001). The use of prescription drugs was more prevalent among xerostomia patients (65%) than among non-xerostomia patients (35%; P<0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 ± 10.0) than those without xerostomia (12.9 ± 8.0; P<0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 ± 0.7) than those without xerostomia (0.7 ± 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients.

Vasoregression: A Shared Vascular Pathology Underlying Macrovascular And Microvascular Pathologies?

PubMed Central

Gupta, Akanksha

2015-01-01

Abstract Vasoregression is a common phenomenon underlying physiological vessel development as well as pathological microvascular diseases leading to peripheral neuropathy, nephropathy, and vascular oculopathies. In this review, we describe the hallmarks and pathways of vasoregression. We argue here that there is a parallel between characteristic features of vasoregression in the ocular microvessels and atherosclerosis in the larger vessels. Shared molecular pathways and molecular effectors in the two conditions are outlined, thus highlighting the possible systemic causes of local vascular diseases. Our review gives us a system-wide insight into factors leading to multiple synchronous vascular diseases. Because shared molecular pathways might usefully address the diagnostic and therapeutic needs of multiple common complex diseases, the literature analysis presented here is of broad interest to readership in integrative biology, rational drug development and systems medicine. PMID:26669709

EMMPRIN modulates epithelial barrier function through a MMP-mediated occludin cleavage: implications in dry eye disease.

PubMed

Huet, Eric; Vallée, Benoit; Delbé, Jean; Mourah, Samia; Prulière-Escabasse, Virginie; Tremouilleres, Magali; Kadomatsu, Kenji; Doan, Serge; Baudouin, Christophe; Menashi, Suzanne; Gabison, Eric E

2011-09-01

Dry eye is a common disease that develops as a result of alteration of tear fluid, leading to osmotic stress and a perturbed epithelial barrier. Matrix metalloproteinase-9 (MMP-9) may be important in dry eye disease, as its genetic knockout conferred resistance to the epithelial disruption. We show that extracellular matrix metalloproteinase inducer (EMMPRIN; also termed CD147), an inducer of MMP expression, participates in the pathogenesis of dry eye through MMP-mediated cleavage of occludin, an important component of tight junctions. EMMPRIN expression was increased on the ocular surface of dry eye patients and correlated with those of MMP-9. High osmolarity in cell culture, mimicking dry eye conditions, increased both EMMPRIN and MMP-9 and resulted in the disruption of epithelial junctions through the cleavage of occludin. Exogenously added recombinant EMMPRIN had similar effects that were abrogated in the presence of the MMP inhibitor marimastat. Membrane occludin immunostaining was markedly increased in the apical corneal epithelium of both EMMPRIN and MMP-9 knock-out mice. Furthermore, an inverse correlation between EMMPRIN and occludin membrane staining was consistently observed both in vitro and in vivo as a function of corneal epithelial cells differentiation. These data suggest a possible role of EMMPRIN in regulating the amount of occludin at the cell surface in homeostasis beyond pathological situations such as dry eye disease, and EMMPRIN may be essential for the formation and maintenance of organized epithelial structure. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Protective Effects of Morus alba Leaves Extract on Ocular Functions of Pups from Diabetic and Hypercholesterolemic Mother Rats

PubMed Central

El-Sayyad, H.I.H.; El-Sherbiny, M.A.; Sobh, M.A.; Abou-El-Naga, A.M.; Ibrahim, M.A.N.; Mousa, S.A.

2011-01-01

Phytotherapy is frequently considered to be less toxic and free from side effects than synthetic drugs. Hence, the present study was designed to investigate the protective use of crude water extract of Morus alba leaves on ocular functions including cataractogenesis, biochemical diabetic and hypercholesterolemic markers, retinal neurotransmitters and retinopathy of rat pups maternally subjected to either diabetes and/or hypercholesterolemia. Application of crude water extract of Morus alba resulted in amelioration of the alterations of maternal serum glucose, LDL, HDL, total cholesterol and creatine phosphokinase activity as well as retinal neurotransmitters including acetylcholine (ACE), adrenaline (AD), nor-adrenaline (NAD), serotonin (5-HT), histamine (HS), dopamine (DA) and gamma amino butyric acid (GABA). The retina of pups of either diabetic and/or hypercholesterolemia mothers exhibited massive alterations of retinal neurotransmitters. The alterations of retinal neurotransmitters were correlated with the observed pathological alterations of retinal pigmented epithelium, photoreceptor inner segment and ganglion cells and increased incidence of DNA fragmentation and apoptosis cell death. However, protection with Morus alba extract led to amelioration of the pathological alterations of retinal neurons and estimated neurotransmitters. Furthermore, a striking incidence of cataract was detected in pups of either diabetic and/or hypercholesterolemic mothers. Highest cataractogenesis was observed in pups of combined -treated groups. Our data indicate that experimental maternal diabetes alone or in combination with hypercholesterolemia led to alteration in the ocular structures of their pups, with an increasing incidence of cataract and retinopathy, and the effects of the extract might be attributed to the hypoglycaemic, antihypercholesterolemic and anti-oxidative potential of flavonoids, the major components of the plant extract. PMID:21697998

Protective effects of Morus alba leaves extract on ocular functions of pups from diabetic and hypercholesterolemic mother rats.

PubMed

El-Sayyad, H I H; El-Sherbiny, M A; Sobh, M A; Abou-El-Naga, A M; Ibrahim, M A N; Mousa, S A

2011-01-01

Phytotherapy is frequently considered to be less toxic and free from side effects than synthetic drugs. Hence, the present study was designed to investigate the protective use of crude water extract of Morus alba leaves on ocular functions including cataractogenesis, biochemical diabetic and hypercholesterolemic markers, retinal neurotransmitters and retinopathy of rat pups maternally subjected to either diabetes and/or hypercholesterolemia. Application of crude water extract of Morus alba resulted in amelioration of the alterations of maternal serum glucose, LDL, HDL, total cholesterol and creatine phosphokinase activity as well as retinal neurotransmitters including acetylcholine (ACE), adrenaline (AD), nor-adrenaline (NAD), serotonin (5-HT), histamine (HS), dopamine (DA) and gamma amino butyric acid (GABA). The retina of pups of either diabetic and/or hypercholesterolemia mothers exhibited massive alterations of retinal neurotransmitters. The alterations of retinal neurotransmitters were correlated with the observed pathological alterations of retinal pigmented epithelium, photoreceptor inner segment and ganglion cells and increased incidence of DNA fragmentation and apoptosis cell death. However, protection with Morus alba extract led to amelioration of the pathological alterations of retinal neurons and estimated neurotransmitters. Furthermore, a striking incidence of cataract was detected in pups of either diabetic and/or hypercholesterolemic mothers. Highest cataractogenesis was observed in pups of combined -treated groups. Our data indicate that experimental maternal diabetes alone or in combination with hypercholesterolemia led to alteration in the ocular structures of their pups, with an increasing incidence of cataract and retinopathy, and the effects of the extract might be attributed to the hypoglycaemic, antihypercholesterolemic and anti-oxidative potential of flavonoids, the major components of the plant extract.

CXCL10 Is Required to Maintain T-Cell Populations and to Control Parasite Replication during Chronic Ocular Toxoplasmosis

PubMed Central

Norose, Kazumi; Kikumura, Akitoshi; Luster, Andrew D.; Hunter, Christopher A.

2011-01-01

Purpose. Toxoplasma gondii is a major cause of ocular disease, which can lead to permanent vision loss in humans. T cells are critically involved in parasite control, but little is known about the molecules that promote T-cell trafficking and migration in the retina. Thus, the aim of this study was to image and dissect the T-cell response during chronic toxoplasmic retinochoroiditis. Methods. C57BL/6 mice were infected with the Me49 strain of T. gondii, and T cells that infiltrated the eye were analyzed by flow cytometry and imaged using multiphoton microscopy. IFN-γ, CXCL9, CXCL10, and CXCR3 mRNA levels were measured by real-time PCR. To investigate the role of CXCL10, mice were treated with anti–CXCL10 antibodies, and histopathology and immunohistochemistry were performed to monitor changes in pathology, cellular infiltration, and parasite burden in the eye. Results. Infection with T. gondii leads to the infiltration of highly activated motile T cells into the eye. These cells express CXCR3 and are capable of producing IFN-γ and TNF-α, and CD8+ T cells express granzyme B. The expression of CXCL9 and CXCL10 in the retina was significantly upregulated during chronic infection. Treatment of chronically infected mice with anti–CXCL10 antibodies led to decreases in the numbers of CD3+, CD4+, and CD8+ T cells and the amount of IFN-γ mRNA expression in the retina and an increase in replicating parasites and ocular pathology. Conclusions. The maintenance of the T-cell response and the control of T. gondii in the eye during chronic infection is dependent on CXCL10. PMID:20811054

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.

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.

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.

Clinicopathologic Assessment of Ocular Adnexal Lymphoproliferative Lesions at a Tertiary Eye Hospital in Iran.

PubMed

Asadi-Amoli, Fahimeh; Nozarian, Zohreh; Bonaki, Hirbod Nasiri; Mehrtash, Vahid; Entezari, Samaneh

2016-01-01

The most common type of ocular lymphoma is non-Hodgkin lymphoma (NHL), categorized into two groups: indolent (slow growing) and aggressive (rapid growing). Differentiating benign reactive lymphoid hyperplasia (RLH) from malignant ocular adnexal lymphoma (OAL) is challenging. Histopathology, immunohistochemistry (IHC) and ow cytometry have been used as diagnostic tools in such cases. In this retrospective case series, from 2002 to 2013 at Farabi Eye Center, 110 patients with ocular lymphoproliferative disease were enrolled. Prevalence, anatomical locations, mean age at diagnosis and the nal diagnosis of the disease with IHC were assessed. Comparison between previous pathologic diagnoses and results of IHC was made. Immunoglobulin light chains and B-cell and T-cell markers and other immuno-phenotyping markers including CD20, CD3, CD5, CD23, CD10, CYCLIND1 and BCL2 were evaluated to determine the most accurate diagnosis. The lymphomas were categorized based on revised European-American lymphoma (REAL) classi cation. Mean age±SD (years) of the patients was 55.6 ±19.3 and 61% were male. Patients with follicular lymphoma, large B-cell lymphoma or chronic lymphocytic leukemia/small cell lymphoma (CLL/SLL) tended to be older. Nine patients with previous diagnoses of low grade B-cell lymphoma were re-evaluated by IHC and the new diagnoses were as follows: extranodal marginal zone lymphoma(EMZL) (n=1), SLL(n=1), mantle cell lymphoma (MCL) (n=3), reactive lymphoid hyperplasia RLH (n=2). Two cases were excluded due to poor blocks. Flow cytometry reports in these seven patients revealed SLL with positive CD5 and CD23, MCL with positive CD5 and CyclinD1 and negative CD23, EMZL with negative CD5,CD23 and CD10. One RLH patient was negative for Kappa/Lambda and positive for CD3 and CD20 and the other was positive for all of the light chains, CD3 and CD20. Orbit (49.1%), conjunctiva (16.1%) and lacrimal glands (16.1%) were the most common sites of involvement. Accurate pathological classi cation of lesions is crucial to determine proper therapeutic approaches. This can be achieved through precise histologic and IHC analyses by expert pathologists.

Inferior oblique muscle paresis as a sign of myasthenia gravis.

PubMed

Almog, Yehoshua; Ben-David, Merav; Nemet, Arie Y

2016-03-01

Myasthenia gravis may affect any of the six extra-ocular muscles, masquerading as any type of ocular motor pathology. The frequency of involvement of each muscle is not well established in the medical literature. This study was designed to determine whether a specific muscle or combination of muscles tends to be predominantly affected. This retrospective review included 30 patients with a clinical diagnosis of myasthenia gravis who had extra-ocular muscle involvement with diplopia at presentation. The diagnosis was confirmed by at least one of the following tests: Tensilon test, acetylcholine receptor antibodies, thymoma on chest CT scan, or suggestive electromyography. Frequency of involvement of each muscle in this cohort was inferior oblique 19 (63.3%), lateral rectus nine (30%), superior rectus four (13.3%), inferior rectus six (20%), medial rectus four (13.3%), and superior oblique three (10%). The inferior oblique was involved more often than any other muscle (p<0.01). Eighteen (60%) patients had ptosis, six (20%) of whom had bilateral ptosis. Diagnosing myasthenia gravis can be difficult, because the disease may mimic every pupil-sparing pattern of ocular misalignment. In addition diplopia caused by paresis of the inferior oblique muscle is rarely encountered (other than as a part of oculomotor nerve palsy). Hence, when a patient presents with vertical diplopia resulting from an isolated inferior oblique palsy, myasthenic etiology should be highly suspected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Morphologic analysis of artifacts in human fetal eyes confounding histopathologic investigations.

PubMed

Herwig, Martina C; Müller, Annette M; Holz, Frank G; Loeffler, Karin U

2011-04-25

Human fetal eyes are an excellent source for studies of the normal ocular development and for examining early ocular changes associated with various syndromes in the context of a pediatric pathologic or prenatal sonographic diagnosis. However, artifacts caused by different factors often render an exact interpretation difficult. In this study, the frequency and extent of artifacts in human fetal eyes were investigated with the aim of distinguishing more precisely these artifacts from real findings, allowing also for a more diligent forensic interpretation. The cohort included 341 fetal eyes, ranging in age from 8 to 38 weeks of gestation, that were investigated macroscopically and by light microscopy. In most specimens, artifacts such as pigment spillage and autolytic changes of the retina were noted. Nearly all specimens showed changes of the lens with remarkable similarities to cataractous lenses in adult eyes. Structural ocular changes associated with systemic syndromes were also observed and in most instances could be distinguished from artifacts. Morphologic changes in fetal eyes should be classified in artifacts caused by way of abortion, mechanical effects from the removal of the eyes, delayed fixation with autolysis, and the fixative itself and should be distinguished from genuine structural abnormalities associated with ocular or systemic disease. This classification can be fairly difficult and requires experience. In addition, lens artifacts are often misleading, and the diagnosis of a fetal cataract should not be made based on histopathologic examination alone.

Ocular Fundus Photography as a Tool to Study Stroke and Dementia.

PubMed

Cheung, Carol Y; Chen, Christopher; Wong, Tien Y

2015-10-01

Although cerebral small vessel disease has been linked to stroke and dementia, due to limitations of current neuroimaging technology, direct in vivo visualization of changes in the cerebral small vessels (e.g., cerebral arteriolar narrowing, tortuous microvessels, blood-brain barrier damage, capillary microaneurysms) is difficult to achieve. As the retina and the brain share similar embryological origin, anatomical features, and physiologic properties with the cerebral small vessels, the retinal vessels offer a unique and easily accessible "window" to study the correlates and consequences of cerebral small vessel diseases in vivo. The retinal microvasculature can be visualized, quantified and monitored noninvasively using ocular fundus photography. Recent clinic- and population-based studies have demonstrated a close link between retinal vascular changes seen on fundus photography and stroke and dementia, suggesting that ocular fundus photography may provide insights to the contribution of microvascular disease to stroke and dementia. In this review, we summarize current knowledge on retinal vascular changes, such as retinopathy and changes in retinal vascular measures with stroke and dementia as well as subclinical makers of cerebral small vessel disease, and discuss the possible clinical implications of these findings in neurology. Studying pathologic changes of retinal blood vessels may be useful for understanding the etiology of various cerebrovascular conditions; hence, ocular fundus photography can be potentially translated into clinical practice. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

PREVALENCE AND PATHOLOGIC FEATURES OF CHLAMYDIA PECORUM INFECTIONS IN SOUTH AUSTRALIAN KOALAS (PHASCOLARCTOS CINEREUS).

PubMed

Speight, K Natasha; Polkinghorne, Adam; Penn, Rachel; Boardman, Wayne; Timms, Peter; Fraser, Tamieka; Johnson, Kathryn; Faull, Rachel; Bate, Sarah; Woolford, Lucy

2016-04-28

Chlamydia pecorum infection is highly prevalent in many koala ( Phascolarctos cinereus ) populations in the eastern states of Australia, causing ocular and urogenital tract disease. In contrast, the current prevalence of chlamydiosis in South Australian (SA) koalas is largely unknown, with few reports of clinical cases. We examined 65 SA rescued wild koalas at necropsy and collected ocular and urogenital swabs for the detection of C. pecorum by PCR. We detected C. pecorum in ocular or urogenital swabs from 57 koalas (88%), and 34 koalas were positive at both ocular and urogenital sites. Clinically overt chlamydial disease was present in only 12 (21%) positive koalas. Gross lesions were often externally inapparent as they affected the urogenital tract (n=5), and 24 infected koalas had microscopically evident lesions only. Lesions were predominantly mild and included conjunctivitis, cystitis, and urethritis. Reproductive tract disease was infrequently observed. We detected C. pecorum in 16 (28%) koalas with no evidence of chlamydial disease, suggesting the presence of subclinical carriers in this population. Based on these findings, chlamydiosis has a higher occurrence in SA koala populations than previously thought, but is most often mild and does not always result in overt clinical disease; inapparent and subclinical infections appear common. Further studies of the prevalence in wild-caught SA koalas are needed along with research into the host and bacterial factors that may influence disease outcome in these animals.

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.

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.

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

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.

[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.

Slime-producing Staphylococcus epidermidis and S. aureus in acute bacterial conjunctivitis in soft contact lens wearers.

PubMed

Catalanotti, Piergiorgio; Lanza, Michele; Del Prete, Antonio; Lucido, Maria; Catania, Maria Rosaria; Gallè, Francesca; Boggia, Daniela; Perfetto, Brunella; Rossano, Fabio

2005-10-01

In recent years, an increase in ocular pathologies related to soft contact lens has been observed. The most common infectious agents were Staphylococcus spp. Some strains produce an extracellular polysaccharidic slime that can cause severe infections. Polysaccharide synthesis is under genetic control and involves a specific intercellular adhesion (ica) locus, in particular, icaA and icaD genes. Conjunctival swabs from 97 patients with presumably bacterial bilateral conjunctivitis, wearers of soft contact lenses were examined. We determined the ability of staphylococci to produce slime, relating it to the presence of icaA and icaD genes. We also investigated the antibiotic susceptibility and Pulsed Field Gel Electrophoresis (PFGE) patterns of the clinical isolates. We found that 74.1% of the S. epidermidis strains and 61.1% of the S. aureus strains isolated were slime producers and showed icaA and icaD genes. Both S. epidermidis and S. aureus slime-producing strains exhibited more surface hydrophobicity than non-producing slime strains. The PFGE patterns overlapped in S. epidermidis strains with high hydrophobicity. The similar PFGE patterns were not related to biofilm production. We found scarce matching among the Staphylococcus spp. studied, slime production, surface hydrophobicity and antibiotic susceptibility.

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.

Development of TWO HD Vapor Exposure Techniques in a Rabbit Ocular Model: A Pilot Study

DTIC Science & Technology

2008-05-01

descriptive pathology report was performed; however, scores were given as outlined in the Methods section for corneal ulceration, necrosis ...regardless of vapor application method. Corneal epithelial necrosis was reported in only one rabbit (#21), the 4-minute VC. There appeared to be no...corneal endothelium damage or stromal necrosis associated with either duration of HD exposure or vapor application, indicating that although damages to

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

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

An enhanced functional ability questionnaire (faVIQ) to measure the impact of rehabilitation services on the visually impaired

PubMed Central

Wolffsohn, James Stuart; Jackson, Jonathan; Hunt, Olivia Anne; Cottriall, Charles; Lindsay, Jennifer; Gilmour, Richard; Sinclair, Anne; Harper, Robert

2014-01-01

AIM To develop a short, enhanced functional ability Quality of Vision (faVIQ) instrument based on previous questionnaires employing comprehensive modern statistical techniques to ensure the use of an appropriate response scale, items and scoring of the visual related difficulties experienced by patients with visual impairment. METHODS Items in current quality-of-life questionnaires for the visually impaired were refined by a multi-professional group and visually impaired focus groups. The resulting 76 items were completed by 293 visually impaired patients with stable vision on two occasions separated by a month. The faVIQ scores of 75 patients with no ocular pathology were compared to 75 age and gender matched patients with visual impairment. RESULTS Rasch analysis reduced the faVIQ items to 27. Correlation to standard visual metrics was moderate (r=0.32-0.46) and to the NEI-VFQ was 0.48. The faVIQ was able to clearly discriminate between age and gender matched populations with no ocular pathology and visual impairment with an index of 0.983 and 95% sensitivity and 95% specificity using a cut off of 29. CONCLUSION The faVIQ allows sensitive assessment of quality-of-life in the visually impaired and should support studies which evaluate the effectiveness of low vision rehabilitation services. PMID:24634868

An enhanced functional ability questionnaire (faVIQ) to measure the impact of rehabilitation services on the visually impaired.

PubMed

Wolffsohn, James Stuart; Jackson, Jonathan; Hunt, Olivia Anne; Cottriall, Charles; Lindsay, Jennifer; Gilmour, Richard; Sinclair, Anne; Harper, Robert

2014-01-01

To develop a short, enhanced functional ability Quality of Vision (faVIQ) instrument based on previous questionnaires employing comprehensive modern statistical techniques to ensure the use of an appropriate response scale, items and scoring of the visual related difficulties experienced by patients with visual impairment. Items in current quality-of-life questionnaires for the visually impaired were refined by a multi-professional group and visually impaired focus groups. The resulting 76 items were completed by 293 visually impaired patients with stable vision on two occasions separated by a month. The faVIQ scores of 75 patients with no ocular pathology were compared to 75 age and gender matched patients with visual impairment. Rasch analysis reduced the faVIQ items to 27. Correlation to standard visual metrics was moderate (r=0.32-0.46) and to the NEI-VFQ was 0.48. The faVIQ was able to clearly discriminate between age and gender matched populations with no ocular pathology and visual impairment with an index of 0.983 and 95% sensitivity and 95% specificity using a cut off of 29. The faVIQ allows sensitive assessment of quality-of-life in the visually impaired and should support studies which evaluate the effectiveness of low vision rehabilitation services.

Identification of spectral phenotypes in age-related macular degeneration patients

NASA Astrophysics Data System (ADS)

Davis, Bert; Russell, Steven; Abramoff, Michael; Nemeth, Sheila C.; Barriga, E. Simon; Soliz, Peter

2007-02-01

The purpose of this study is to show that there exists a spectral characteristic that differentiates normal macular tissue from various types of genetic-based macular diseases. This paper demonstrates statistically that hyperspectral images of macular and other retinal tissue can be used to spectrally differentiate different forms of age-related macular degeneration. A hyperspectral fundus imaging device has been developed and tested for the purpose of collecting hyperspectral images of the human retina. A methodology based on partial least squares and ANOVA has been applied to determine the hyperspectral representation of individual spectral characteristics of retinal features. Each discrete tissue type in the retina has an identifiable spectral shape or signature which, when combined with spatial context, aids in detection of pathological features. Variations in the amount and distribution of various ocular pigments or the inclusion of additional biochemical substances will allow detection of pathological conditions prior to traditional histological presentation. Fundus imaging cameras are ubiquitous and are one of the most common imaging modalities used in documenting a patient's retinal state for diagnosis, e.g. remotely, or for monitoring the progression of an ocular disease. The added diagnostic information obtained with only a minor retro-fit of a specialized spectral camera will lead to new diagnostic information to the clinical ophthalmologist or eye-care specialist.

Recurrent conjunctivitis as a presentation of munchausen syndrome by proxy.

PubMed

Baskin, Darrell E; Stein, Fernando; Coats, David K; Paysse, Evelyn A

2003-08-01

To report a case of Munchausen syndrome by proxy, which manifested as recurrent bilateral keratoconjunctivitis in an infant. Interventional case report. The patient underwent numerous diagnostic studies, including two endoscopies, skin biopsy, conjunctival pH measurement, and a skeletal survey. She underwent daily eye examinations until the corneal and conjunctival epithelial defects resolved. Resolution of cutaneous, mucosal, corneal, and conjunctival epithelial defects. A punch biopsy of the right postauricular area was performed, and pathology subsequently determined that the findings seemed to be the result of an exogenous injury. The conjunctival pH was 8.0, consistent with exposure to an exogenous, caustic agent. The acute ocular lesions resolved. Munchausen syndrome by proxy can be seen with ophthalmic manifestations and should be considered in the differential diagnosis when ocular abnormalities cannot be explained after a thorough and methodical evaluation.

Ocular histopathology in Eastern equine encephalitis: A case report.

PubMed

Lad, Eleonora M; Ong, Sally S; Proia, Alan D

2017-04-01

To describe the ophthalmic symptoms and histopathological findings in a human case of Eastern equine encephalitis (EEE). The patient was a septuagenarian male whose presentation and clinical course were thought to be most consistent with viral meningoencephalitis. ELISA suggested recent infection with EEE virus. Microscopic analysis of the brain demonstrated perivascular lymphohistiocytic cuffing which was consistent with viral type encephalitis. Similarly, both eyes manifested a lymphohistiocytic infiltrate in the retina and optic nerve and a reduced number of ganglion cells. To our knowledge, this is the first report of ophthalmological and ocular pathology observations in an EEE patient. Interestingly, the inflammatory findings in the retina are reminiscent of the central nervous system effects of EEE virus. These findings are relevant given the recent epidemic of microcephaly and ophthalmic complications secondary to another arboviral virus, the Zika virus.

Antiadhesive Character of Mucin O-glycans at the Apical Surface of Corneal Epithelial Cells

PubMed Central

Sumiyoshi, Mika; Ricciuto, Jessica; Tisdale, Ann; Gipson, Ilene K.; Mantelli, Flavio; Argüeso, Pablo

2008-01-01

Purpose Prolonged contact of opposite mucosal surfaces, which occurs on the ocular surface, oral cavity, reproductive tract, and gut, requires a specialized apical cell surface that prevents adhesion. The purpose of this study was to evaluate the contribution of mucin O-glycans to the antiadhesive character of human corneal–limbal epithelial (HCLE) cells. Methods Mucin O-glycan biosynthesis in HCLE cells was disrupted by metabolic interference with benzyl-α-GalNAc. The cell surface mucin MUC16 and its carbohydrate epitope H185 were detected by immunofluorescence and Western blot. HCLE cell surface features were assessed by field emission scanning electron microscopy. Cell–cell adhesion assays were performed under static conditions and in a parallel plate laminar flow chamber. Results Benzyl-α-GalNAc disrupted the biosynthesis of O-glycans without affecting apomucin biosynthesis or cell surface morphology. Static adhesion assays showed that the apical surface of differentiated HCLE cells expressing MUC16 and H185 was more antiadhesive than undifferentiated HCLE cells, which lacked MUC16. Abrogation of mucin O-glycosylation in differentiated cultures with benzyl-α-GalNAc resulted in increased adhesion of applied corneal epithelial cells and corneal fibroblasts. The antiadhesive effect of mucin O-glycans was further demonstrated by fluorescence video microscopy in dynamic flow adhesion assays. Cationized ferritin labeling of the cell surface indicated that anionic repulsion did not contribute to the antiadhesive character of the apical surface. Conclusions These results indicate that epithelial O-glycans contribute to the antiadhesive properties of cell surface–associated mucins in corneal epithelial cells and suggest that alterations in mucin O-glycosylation are involved in the pathology of drying mucosal diseases (e.g., dry eye). PMID:18172093

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.

A new experimental device to evaluate eye ulcers using a multispectral electrical impedance technique

NASA Astrophysics Data System (ADS)

Bellotti, Mariela I.; Bast, Walter; Berra, Alejandro; Bonetto, Fabián J.

2011-07-01

We present a novel experimental technique to determine eye ulcers in animals using a spectral electrical impedance technique. We expect that this technique will be useful in dry eye syndrome. We used a sensor that is basically a platinum (Pt) microelectrode electrically insulated by glass from a cylindrical stainless steel counter-electrode. This sensor was applied to the naked eye of New Zealand rabbits (2.0-3.5 kg in weight). Whereas half of the eyes were normal (control), we applied to the remainder a few drops of 20% (v/v) alcohol to produce an ulcer in the eye. Using a multispectral electrical impedance system we measured ulcerated and control eyes and observed significant difference between normal and pathological samples. We also investigated the effects of different applied pressures and natural degradation of initially normal eyes as a function of time. We believe that this technique could be sufficiently sensitive and repetitive to help diagnose ocular surface diseases such as dry eye syndrome.

A new experimental device to evaluate eye ulcers using a multispectral electrical impedance technique.

PubMed

Bellotti, Mariela I; Bast, Walter; Berra, Alejandro; Bonetto, Fabián J

2011-07-01

We present a novel experimental technique to determine eye ulcers in animals using a spectral electrical impedance technique. We expect that this technique will be useful in dry eye syndrome. We used a sensor that is basically a platinum (Pt) microelectrode electrically insulated by glass from a cylindrical stainless steel counter-electrode. This sensor was applied to the naked eye of New Zealand rabbits (2.0-3.5 kg in weight). Whereas half of the eyes were normal (control), we applied to the remainder a few drops of 20% (v/v) alcohol to produce an ulcer in the eye. Using a multispectral electrical impedance system we measured ulcerated and control eyes and observed significant difference between normal and pathological samples. We also investigated the effects of different applied pressures and natural degradation of initially normal eyes as a function of time. We believe that this technique could be sufficiently sensitive and repetitive to help diagnose ocular surface diseases such as dry eye syndrome.

Ultrasonic evaluation of orbito-ocular trauma in Benin-City, Nigeria.

PubMed

Eze, K C; Enock, M E; Eluehike, S U

2009-09-01

To find out the causes, time of presentation for ultrasound scan, pattern of eye injuries and orbital ultrasound findings in patients with orbito-ocular trauma. Retrospective study of request cards, case notes and ultrasound reports of 67 patients who had trauma to the eye and were assessed with ultrasonography over a 3-year period (between 20th January 2000 and 19th January 2003) was done. The collected data included age, sex, presenting complaint, past medical history, duration of the injury before presentation to ultrasonographic study and ultrasound findings. Sixty-seven patients were seen consisting of 54 males (83.58%) and 11 females (16.42%) with male to female ratio of 5:1. Age range was 4 to 91 years with mean age of 30.8 years. 44 patients (65. 67%) had blunt trauma while 23 patients (34.32%) had penetrating trauma. The causes of the ocular trauma include road traffic accidents 32 (47.76%), assaults 16 (23.88%), gunshot injuries 10 (14. 93%), sports injuries 5 (7.46%), and falls from heights 4 (5.92%) patients. 42 patients (53.73%), especially those with severe injuries presented late for ultrasonography. Those who made early presentation were cases of assault because of police involvement. Forty-five patients (67.16%) had structurally identifiable pathology in one or both eyes. Retinal detachment 18 (26.87%), vitreous haemorrhage 17 (25.37%), traumatic cataract 13 (19.40), ruptured globe 6 (8.96%) and posterior dislocation of the lens 6 (8.96) were the commonest abnormal sonographic findings. In 22 patients (32.84%) both eyes were normal. Ultrasound scan is a useful imaging modality for examination of the globe in patients with ocular trauma. Road traffic accident is the commonest cause of traumatic ocular injury affecting the globe. Retinal detachment and vitreous haemorrhage are the most frequent injuries to the globe diagnosed by ultrasound scan. Measures to reduce road traffic accidents will have far reaching positive effect in preventing blindness resulting from orbito-ocular trauma in Nigeria.

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.

Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in different geographical regions.

PubMed

Chanudet, E; Zhou, Y; Bacon, C M; Wotherspoon, A C; Müller-Hermelink, H-K; Adam, P; Dong, H Y; de Jong, D; Li, Y; Wei, R; Gong, X; Wu, Q; Ranaldi, R; Goteri, G; Pileri, S A; Ye, H; Hamoudi, R A; Liu, H; Radford, J; Du, M-Q

2006-07-01

Infectious agents play a critical role in MALT lymphoma development. Studies from Italy showed Chlamydia psittaci infection in 87% of ocular adnexal MALT lymphomas and complete or partial regression of the lymphoma after C. psittaci eradication in four of nine cases. However, C. psittaci was not demonstrated in ocular adnexal MALT lymphomas from the USA. This study was thus designed to investigate further the role of C. psittaci, and other infectious agents commonly associated with chronic eye disease, in the development of ocular adnexal MALT lymphoma. The presence of C. psittaci, C. trachomatis, C. pneumoniae, herpes simplex virus 1 and 2 (HSV1, HSV2), and adenovirus 8 and 19 (ADV8, ADV19) was assessed separately by polymerase chain reaction in 142 ocular adnexal MALT lymphomas, 53 non-marginal zone lymphomas, and 51 ocular adnexal biopsies without a lymphoproliferative disorder (LPD), from six geographical regions. C. psittaci was detected at similar low frequencies in non-LPD and non-marginal zone lymphoma groups from different geographical regions (0-14%). Overall, the prevalence of C. psittaci was significantly higher in MALT lymphomas (22%) than in non-LPD (10%, p=0.042) and non-marginal zone lymphoma cases (9%, p=0.033). However, the prevalence of C. psittaci infection in MALT lymphoma showed marked variation among the six geographical regions examined, being most frequent in Germany (47%), followed by the East Coast of the USA (35%) and the Netherlands (29%), but relatively low in Italy (13%), the UK (12%), and Southern China (11%). No significant differences in the detection of C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8, and ADV19 were found between lymphomas and controls from different geographical regions. In conclusion, our results show that C. psittaci, but not C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8 or ADV19, is associated with ocular adnexal MALT lymphoma and that this association is variable in different geographical areas. Copyright (c) 2006 Pathological Society of Great Britain and Ireland.

Determination of retinal surface area.

PubMed

Nagra, Manbir; Gilmartin, Bernard; Thai, Ngoc Jade; Logan, Nicola S

2017-09-01

Previous attempts at determining retinal surface area and surface area of the whole eye have been based upon mathematical calculations derived from retinal photographs, schematic eyes and retinal biopsies of donor eyes. 3-dimensional (3-D) ocular magnetic resonance imaging (MRI) allows a more direct measurement, it can be used to image the eye in vivo, and there is no risk of tissue shrinkage. The primary purpose of this study is to compare, using T2-weighted 3D MRI, retinal surface areas for superior-temporal (ST), inferior-temporal (IT), superior-nasal (SN) and inferior-nasal (IN) retinal quadrants. An ancillary aim is to examine whether inter-quadrant variations in area are concordant with reported inter-quadrant patterns of susceptibility to retinal breaks associated with posterior vitreous detachment (PVD). Seventy-three adult participants presenting without retinal pathology (mean age 26.25 ± 6.06 years) were scanned using a Siemens 3-Tesla MRI scanner to provide T2-weighted MR images that demarcate fluid-filled internal structures for the whole eye and provide high-contrast delineation of the vitreous-retina interface. Integrated MRI software generated total internal ocular surface area (TSA). The second nodal point was used to demarcate the origin of the peripheral retina in order to calculate total retinal surface area (RSA) and quadrant retinal surface areas (QRSA) for ST, IT, SN, and IN quadrants. Mean spherical error (MSE) was -2.50 ± 4.03D and mean axial length (AL) 24.51 ± 1.57 mm. Mean TSA and RSA for the RE were 2058 ± 189 and 1363 ± 160 mm 2 , respectively. Repeated measures anova for QRSA data indicated a significant difference within-quadrants (P < 0.01) which, contrasted with ST (365 ± 43 mm 2 ), was significant for IT (340 ± 40 mm 2 P < 0.01), SN (337 ± 40 mm 2 P < 0.01) and IN (321 ± 39 mm 2 P < 0.01) quadrants. For all quadrants, QRSA was significantly correlated with AL (P < 0.01) and exhibited equivalent increases in retinal area/mm increase in AL. Although the differences between QRSAs are relatively small, there was evidence of concordance with reported inter-quadrant patterns of susceptibility to retinal breaks associated with PVD. The data allow AL to be converted to QRSAs, which will assist further work on inter-quadrant structural variation. © 2017 Anatomical Society.

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.

Differentiation of ocular fundus fluorophores by fluorescence lifetime imaging using multiple excitation and emission wavelengths

NASA Astrophysics Data System (ADS)

Hammer, M.; Schweitzer, D.; Schenke, S.; Becker, W.; Bergmann, A.

2006-10-01

Ocular fundus autofluorescence imaging has been introduced into clinical diagnostics recently. It is in use for the observation of the age pigment lipofuscin, a precursor of age - related macular degeneration (AMD). But other fluorophores may be of interest too: The redox pair FAD - FADH II provides information on the retinal energy metabolism, advanced glycation end products (AGE) indicate protein glycation associated with pathologic processes in diabetes as well as AMD, and alterations in the fluorescence of collagen and elastin in connective tissue give us the opportunity to observe fibrosis by fluorescence imaging. This, however, needs techniques able to differentiate particular fluorophores despite limited permissible ocular exposure as well as excitation wavelength (limited by the transmission of the human ocular lens to >400 nm). We present an ophthalmic laser scanning system (SLO), equipped with picosecond laser diodes (FWHM 100 ps, 446 nm or 468 nm respectively) and time correlated single photon counting (TCSPC) in two emission bands (500 - 560 nm and 560 - 700 nm). The decays were fitted by a bi-exponential model. Fluorescence spectra were measured by a fluorescence spectrometer fluorolog. Upon excitation at 446 nm, the fluorescence of AGE, FAD, and lipofuscin were found to peak at 503 nm, 525 nm, and 600 nm respectively. Accordingly, the statistical distribution of the fluorescence decay times was found to depend on the different excitation wavelengths and emission bands used. The use of multiple excitation and emission wavelengths in conjunction with fluorescence lifetime imaging allows us to discriminate between intrinsic fluorophores of the ocular fundus. Taken together with our knowledge on the anatomical structure of the fundus, these findings suggest an association of the short, middle and long fluorescence decay time to the retinal pigment epithelium, the retina, and connective tissue respectively.

Subclinical vestibular dysfunction in migraine patients: a preliminary study of ocular and rectified cervical vestibular evoked myogenic potentials.

PubMed

Kim, Chul-Ho; Jang, Min-Uk; Choi, Hui-Chul; Sohn, Jong-Hee

2015-01-01

Many studies have identified various vestibular symptoms and laboratory abnormalities in migraineurs. Although the vestibular tests may be abnormal, the changes may exist without vestibular symptoms. To date, vestibular-evoked myogenic potential (VEMP) has been the easiest and simplest test for measuring vestibular function in clinical practice. Cervical VEMP (cVEMP) represents a vestibulo-collic reflex, whereas ocular VEMP (oVEMP) reflects a vestibulo-ocular pathway. Therefore, we determined whether ocular and rectified cervical VEMPs differed in patients with migraine or tension type headache (TTH) and compared the results to controls with no accompanying vestibular symptoms. The present study included 38 females with migraine without aura, 30 with episodic TTH, and 50 healthy controls without vestibular symptoms. oVEMP and cVEMP using a blood pressure manometer were recorded during a headache-free period. From the VEMP graphs, latency and amplitude parameters were analyzed, especially following EMG rectification in cVEMP. With respect to oVEMP, the migraine group exhibited significantly longer mean latencies of bilateral n1 and left p1 than the other groups (p < 0.05). Amplitudes of n1-p1 were lower than in other groups, but the difference did not reach statistical significance. In regards to cVEMP, p13 and n23 latencies and amplitudes after rectification did not differ significantly among groups. An abnormal interictal oVEMP profile was associated with subclinical vestibular dysfunction in migraineurs, suggesting pathology within the vestibulo-ocular reflex. oVEMP is a more reliable measure than cVEMP to evaluate vestibular function in migraineurs, although results from the two tests in patients with migraine are complementary.

Ocular dimensions in relation to auxological data in a sample of Swedish children aged 4-15 years.

PubMed

Raffa, Lina H; Hellström, Ann; Aring, Eva; Andersson, Susann; Grönlund, Marita Andersson

2014-11-01

The purpose was to characterize normal growth patterns of ocular and optical components and to relate them to auxological data in a sample of Swedish children aged 4-15 years. A prospective cross-sectional study was carried out in 143 Swedish children with a mean age of 9.8 years. Variables including gestational age (GA), weight, length and head circumference (HCF) at birth and at the time of assessment were registered. Visual acuity (VA), cycloplegic refraction and biometric measures were obtained. Palpebral fissure length and inner canthal distance were measured. Optic disc morphology as seen on fundus photographs was analysed. Children born more mature, with male predilection, were found to have deeper anterior and vitreous chamber depths, longer axial lengths and thinner crystalline lens thickness. No correlations were found between ocular biometric measurements and VA or refraction after adjustment for confounding variables. Inner canthal distance was significantly correlated with birth length (p = 0.03), height, weight, BMI and HCF (p = 0.0008, p = 0.0007, p = 0.037, and p = 0.04, respectively) at time of assessment. Total axial length was found to be significantly correlated with GA (p = 0.0226) and length at assessment in girls (p = 0.0084). Right optic disc and rim areas decreased with increasing age (p = 0.0078 and p = 0.0107, respectively); however, optic disc parameters were not dependent on any other variable. These normative values may serve as a basis for the ocular findings and their relationship to auxological data in Caucasian children aged 4-15 years, as well as for future comparison in patients with paediatric ocular pathologies. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

[Magnetic resonance imaging and ultrasonography in dogs and cats with ocular and orbital diseases. Part 1: Ocular diseases].

PubMed

von Krosigk, F; Steinmetz, A; Ellenberger, C; Oechtering, G

2012-01-01

This two-part study describes the clinical usefulness and value of ultrasound and magnetic resonance imaging (MRI) in dogs and cats with ocular (n=30) and orbital diseases (n=31). MRI and ultrasonography characteristics are described in single cases with ocular and orbital disease. Ultrasonography and MRI were performed in 15 dogs and 15 cats with intraocular neoplasia or intraocular inflammatory disease. In all patients with intraocular neoplasia, sonography revealed masses with increased echogenicity and fairly uniform echotexture, thus allowing the tentative diagnosis of an intraocular tumour. In these cases, MRI often proved to be a valuable diagnostic tool in showing the complete extent of intraocular lesion. An additional benefit of MRI was seen in the tissue characterization of tumours based on MRI signal characteristics and pattern of contrast enhancement. Discreet intraocular inflammatory alterations, in particular to the anterior and posterior segment of the eyeball, were more clearly shown by ultrasound than by MRI. Neoplasia could be excluded and inflammatory disease was successfully diagnosed using MRI due to the different image sequences with or without contrast medium administration. Traumatic ruptures of the lens capsule and the globe after trauma were depicted more clearly with MRI. When opacity of the anterior eye segment is present, various intraocular changes can be quickly diagnosed by ultrasound with high accuracy, without requiring anaesthesia of the patient. MRI of the globe allows differentiation of diverse pathologies, gives detailed information of infiltration in orbital structures and the exact degree of ocular lesions after trauma. This additional evidence often makes it easier to predict the correct prognosis and choose the best therapy.

Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome

PubMed Central

Kamiyoshi, Naohiro; Fu, Xue Jun; Morisada, Naoya; Nozu, Yoshimi; Ye, Ming Juan; Imafuku, Aya; Miura, Kenichiro; Yamamura, Tomohiko; Minamikawa, Shogo; Shono, Akemi; Ninchoji, Takeshi; Morioka, Ichiro; Nakanishi, Koichi; Yoshikawa, Norishige; Kaito, Hiroshi; Iijima, Kazumoto

2016-01-01

Background and objectives Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in collagen 4A3 and/or collagen 4A4 accounts for <5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear. Design, setting, participants, & measurements We conducted a retrospective analysis of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (a total of 72 patients) from 16 unrelated families. Patients with suspected Alport syndrome after pathologic examination who were referred from anywhere in Japan for genetic analysis from 2006 to 2015 were included in this study. Clinical, laboratory, and pathologic data were collected from medical records at the point of registration for genetic diagnosis. Genetic analysis was performed by targeted resequencing of 27 podocyte-related genes, including Alport–related collagen genes, to make a diagnosis of autosomal dominant Alport syndrome and identify modifier genes or double mutations. Clinical data were obtained from medical records. Results The median renal survival time was 70 years, and the median age at first detection of proteinuria was 17 years old. There was one patient with hearing loss and one patient with ocular lesion. Among 16 patients who underwent kidney biopsy, three showed FSGS, and seven showed thinning without lamellation of the glomerular basement membrane. Five of 13 detected mutations were reported to be causative mutations for autosomal recessive Alport syndrome in previous studies. Two families possessed double mutations in both collagen 4A3 and collagen 4A4, but no modifier genes were detected among the other podocyte–related genes. Conclusions The renal phenotype of autosomal dominant Alport syndrome was much milder than that of autosomal recessive Alport syndrome or X–linked Alport syndrome in men. It may, thus, be difficult to make an accurate diagnosis of autosomal dominant Alport syndrome on the basis of clinical or pathologic findings. No modifier genes were identified among the known podocyte–related genes. PMID:27281700

Genetic, Clinical, and Pathologic Backgrounds of Patients with Autosomal Dominant Alport Syndrome.

PubMed

Kamiyoshi, Naohiro; Nozu, Kandai; Fu, Xue Jun; Morisada, Naoya; Nozu, Yoshimi; Ye, Ming Juan; Imafuku, Aya; Miura, Kenichiro; Yamamura, Tomohiko; Minamikawa, Shogo; Shono, Akemi; Ninchoji, Takeshi; Morioka, Ichiro; Nakanishi, Koichi; Yoshikawa, Norishige; Kaito, Hiroshi; Iijima, Kazumoto

2016-08-08

Alport syndrome comprises a group of inherited heterogeneous disorders involving CKD, hearing loss, and ocular abnormalities. Autosomal dominant Alport syndrome caused by heterozygous mutations in collagen 4A3 and/or collagen 4A4 accounts for <5% of patients. However, the clinical, genetic, and pathologic backgrounds of patients with autosomal dominant Alport syndrome remain unclear. We conducted a retrospective analysis of 25 patients with genetically proven autosomal dominant Alport syndrome and their family members (a total of 72 patients) from 16 unrelated families. Patients with suspected Alport syndrome after pathologic examination who were referred from anywhere in Japan for genetic analysis from 2006 to 2015 were included in this study. Clinical, laboratory, and pathologic data were collected from medical records at the point of registration for genetic diagnosis. Genetic analysis was performed by targeted resequencing of 27 podocyte-related genes, including Alport-related collagen genes, to make a diagnosis of autosomal dominant Alport syndrome and identify modifier genes or double mutations. Clinical data were obtained from medical records. The median renal survival time was 70 years, and the median age at first detection of proteinuria was 17 years old. There was one patient with hearing loss and one patient with ocular lesion. Among 16 patients who underwent kidney biopsy, three showed FSGS, and seven showed thinning without lamellation of the glomerular basement membrane. Five of 13 detected mutations were reported to be causative mutations for autosomal recessive Alport syndrome in previous studies. Two families possessed double mutations in both collagen 4A3 and collagen 4A4, but no modifier genes were detected among the other podocyte-related genes. The renal phenotype of autosomal dominant Alport syndrome was much milder than that of autosomal recessive Alport syndrome or X-linked Alport syndrome in men. It may, thus, be difficult to make an accurate diagnosis of autosomal dominant Alport syndrome on the basis of clinical or pathologic findings. No modifier genes were identified among the known podocyte-related genes. Copyright © 2016 by the American Society of Nephrology.

Ocular Coherence Tomography in the Evaluation of Anterior Eye Injuries in Space Flight

NASA Technical Reports Server (NTRS)

Fer, Dan M.; Law, Jennifer; Wells, Julia

2017-01-01

While Ocular Coherence Tomography (OCT) is not a first-line modality to evaluate anterior eye structures terrestrially, it is a resource already available on the International Space Station (ISS) that can be used in medical contingencies that involve the anterior eye. With remote guidance and subject matter expert (SME) support from the ground, a minimally trained crewmember can now use OCT to evaluate anterior eye pathologies on orbit. OCT utilizes low-coherence interferometry to produce detailed cross-sectional and 3D images of the eye in real time. Terrestrially, it has been used to evaluate macular pathologies and glaucoma. Since 2013, OCT has been used onboard the ISS as one part of a suite of hardware to evaluate the Visual Impairment/Intracranial Pressure risk faced by astronauts, specifically assessing changes in the retina and choroid during space flight. The Anterior Segment Module (ASM), an add-on lens, was also flown for research studies, providing an opportunity to evaluate the anterior eye in real time if clinically indicated. Anterior eye pathologies that could be evaluated using OCT were identified. These included corneal abrasions and ulcers, scleritis, and acute angle closure glaucoma. A remote guider script was written to provide ground specialists with step-by-step instructions to guide ISS crewmembers, who do not get trained on the ASM, to evaluate the anterior eye. The instructions were tested on novice subjects and/or operators, whose feedback was incorporated iteratively. The final remote guider script was reviewed by SME optometrists and NASA flight surgeons. The novel application of OCT technology to space flight allows for the acquisition of objective data to diagnose anterior eye pathologies when other modalities are not available. This demonstrates the versatility of OCT and highlights the advantages of using existing hardware and remote guidance skills to expand clinical capabilities in space flight.

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.

The contribution of the sclera and lamina cribrosa to the pathogenesis of glaucoma: Diagnostic and treatment implications.

PubMed

Quigley, Harry A

2015-01-01

Glaucoma, the second most common cause of world blindness, results from loss of retinal ganglion cells (RGC). RGC die as a consequence of injury to their axons, as they pass through the transition between the environment within the eye and that of the retrobulbar optic nerve, as they course to central visual centers. At the optic nerve head (ONH), axonal transport becomes abnormal, at least in part due to the effect of strain induced by intraocular pressure (IOP) on the sclera and ONH. Animal glaucoma models provide the ability to study how alterations in ocular connective tissues affect this pathological process. New therapeutic interventions are being investigated to mitigate glaucoma blindness by modifying the remodeling of ocular tissues in glaucoma. Some genetically altered mice are resistant to glaucoma damage, while treatment of the sclera with cross-linking agents makes experimental mouse glaucoma damage worse. Inhibition of transforming growth factor β activity is strikingly protective. Treatments that alter the response of ocular connective tissues to IOP may be effective in protecting those with glaucoma from vision loss. © 2015 Elsevier B.V. All rights reserved.

Microrobots: a new era in ocular drug delivery.

PubMed

Fusco, Stefano; Ullrich, Franziska; Pokki, Juho; Chatzipirpiridis, George; Özkale, Berna; Sivaraman, Kartik M; Ergeneman, Olgaç; Pané, Salvador; Nelson, Bradley J

2014-11-01

Ocular microrobots have the potential to change the way in which we treat a variety of diseases at the anterior and the posterior segments of the eye. Wireless manipulation and positioning of drug delivery magnetic millimeter and submillimeter platforms into the eye constitute a potential route for minimally invasive targeted therapy. However, the field is still in its infancy and faces challenges related to the fabrication, control an interaction with complex biological environments. This review briefly introduces the complex anatomy and physiology of the eye, which renders limitations to the current treatments of ocular diseases. The topical administration of eye drops, intravitreal injections and drug delivery implants is briefly mentioned together with their drawbacks. The authors also analyze the minimally invasive microrobotic approach as an alternative method and report the recent advancements in the fabrication, control, manipulation and drug delivery. Although microrobotics is a young field, a significant amount of work has been developed to face different challenges related to the minimally invasive manipulation of microdevices in the eye. Current research is already at the state of in vivo testing for systems and their biocompatibility. It is expected that the general concepts acquired will soon be applied for specific interventions, especially for posterior eye pathologies.

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.

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.

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.