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.

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.

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

PubMed

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

2015-01-01

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

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.

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

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.

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

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.

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.

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.

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.

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

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

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

PubMed

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

2016-07-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

Dysfunctional tear syndrome (DTS) is a common and complex condition affecting the ocular surface. The health and normal functioning of the ocular surface is dependent on a stable and sufficient tear film. Clinician awareness of conditions affecting the ocular surface has increased in recent years because of expanded research and the publication of diagnosis and treatment guidelines pertaining to disorders resulting in DTS, including the Delphi panel treatment recommendations for DTS (2006), the International Dry Eye Workshop (DEWS) (2007), the Meibomian Gland Dysfunction (MGD) Workshop (2011), and the updated Preferred Practice Pattern guidelines from the American Academy of Ophthalmology pertaining to dry eye and blepharitis (2013). Since the publication of the existing guidelines, new diagnostic techniques and treatment options that provide an opportunity for better management of patients have become available. Clinicians are now able to access a wealth of information that can help them obtain a differential diagnosis and treatment approach for patients presenting with DTS. This review provides a practical and directed approach to the diagnosis and treatment of patients with DTS, emphasizing treatment that is tailored to the specific disease subtype as well as the severity of the condition. PMID:28099212

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

PubMed

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

2014-01-01

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

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.

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.

Immunological impression cytology of the conjunctival epithelium in patients with thyroid orbitopathy-related dry eye.

PubMed

Hsu, S L; Lee, P Y; Chang, C H; Chen, C H

2016-08-30

Thyroid orbitopathy (TO) is an autoimmune disease that is complicated by ocular surface disorders, leading to discomfort. Dry eye is very prevalent in patients with TO. Recent studies on the pathogenesis of dry eye have focused on the inflammatory process, and some supporting evidence has been discovered. Because TO is a disorder of autoimmune origin, we assumed that the association between TO and dry eye is related to inflammation. Inflammation of the ocular surface in TO-related dry eye has not been well studied. In this study, we assessed cellular inflammation of the ocular surface and the cytokine profiles in patients with TO-related dry eye. Conjunctival impression cytology (CIC) was assessed with an immunofluorescent assay. TO-related dry eye was diagnosed by using the Schirmer test, tear break-up time, thyroid function, and clinical signs. CIC was combined with immunological staining of interleukin-1a (IL-1a), IL-1b, and IL- 6. The immunological impression cytology (IC) grade was compared to the clinical activity score of TO. All TO patients with dry eye were positive for IL-1a, IL-1b, and IL-6. However, the normal controls were also positive for IL-1a. A trend was observed between the clinical inflammatory score and immunological IC grade. This study was the first to delineate the immunological IC of TO-related dry eye. Our study aimed to investigate the pathogenesis of dry eye in TO. Our findings suggest that the conjunctival cytokines IL-1a, IL-1b, and IL-6 may play a role. The results of this study will be useful for future studies of additional inflammatory cytokines, and the levels of these cytokines could be used as an outcome to assess the efficacy of treatment, such as anti-cytokine or immunosuppression therapy, in patients with TO-related dry eye or other ocular surface inflammatory disorders.

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.

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.

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

Modified osteo-odonto keratoprosthesis--the Indian experience--results of the first 50 cases.

PubMed

Iyer, Geetha; Pillai, Vinay S; Srinivasan, Bhaskar; Falcinelli, Giovanni; Padmanabhan, Prema; Guruswami, Sitalakshmi; Falcinelli, Giancarlo

2010-07-01

To study the results of the modified osteo-odonto keratoprosthesis (MOOKP) surgery in bilateral end-stage ocular surface disorders. The MOOKP surgery is performed as a routine in 3 stages. Stage 1A involves removal of the iris and anterior vitrectomy with a corneal transplant if indicated. Stage 1B + 1C usually performed simultaneously involves harvesting the buccal mucosa and transplanting it onto the ocular surface along with fashioning of the osteo-odonto alveolar lamina. Stage 2 involves transplanting the osteo-odonto alveolar lamina to the eye 3 months later. The MOOKP surgery was completed in 50 eyes of 47 patients with a mean follow-up of 15.38 months (range: 1-54 months). Anatomic success was achieved in 96% of the eyes. Functional success of visual acuity > or = 20/60 was noted in 66% of eyes. Complications included oroantral fistula (6%), trophic mucosal alterations (8%), lamina exposure (central 6% and peripheral 8%), mucous membrane overgrowth (2%), hypotony (2%), expulsion of optic cylinder (4%), endophthalmitis (2%), glaucoma (20%), sterile vitritis (6%), and retinal detachment (2%). MOOKP is the keratoprosthesis of choice in bilateral end-stage ocular surface disorders in the Indian subcontinent. Complications do occur and have to be recognized and treated early.

[Light protection for xeroderma pigmentosum].

PubMed

Ettinger, M; Berneburg, M

2017-05-01

Xeroderma pigmentosum is a rare autosomal recessive disorder which is caused by germinal mutations responsible for the repair of ultraviolet (UV) radiation-induced DNA lesions. It is characterized by hypersensitivity to UV radiation, poikiloderma, ocular surface disease, and in some patients pronounced sunburn and neurological disease. Patients have a very high risk of developing ocular and skin cancer on exposed body sites. No cure is available for these patients except complete protection from all types of UV radiation.

Ocular allergy and dry eye syndrome.

PubMed

Bielory, Leonard

2004-10-01

Ocular allergy is a common clinical disorder that includes dry eye syndrome in its differential diagnosis. While ocular allergy treatments have continued to evolve since the early 1990s when the new prescription topical agents became available, there have been no major advances in the treatment of dry eye syndrome other than changes in the chemical structures of various artificial tear formulations. This review is timely and relevant due to the recent FDA approval of several new agents for the treatment of dry eye syndrome. The literature reviewed brings the practicing allergist/clinical immunologist up to date on the recent understanding that T-cell activation plays a key role in dry eye syndrome immunopathophysiology. In addition, the parallel novel treatment developments are discussed, including new formulations for tear substitutes, topical cyclosporine A and purinergic receptor (P2Y2) agonists. The recent developments bode well for patients who are referred for ocular allergy, including dry eye syndrome. A new formulation for a tear substitute that generates a 'soft gel' covering the ocular surface (in situ) is ideal for early forms of dry syndrome, while topical cyclosporine is the first new real prescription treatment for patients with moderate to severe forms of dry eye. Another potential agent to revolutionize the treatment of various disorders is based on the discovery of the purinergic receptor agonists. This is not only relevant for the production of mucin and the change in tear fluid content, but it may also have implications for other sinopulmonary disorders such as cystic fibrosis and chronic sinusitis.

Dry Eye Disease: Prevalence, Assessment, and Management.

PubMed

Rouen, Patricia A; White, Mary L

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

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.

Gender Disparities in Ocular Inflammatory Disorders*

PubMed Central

Sen, Hatice Nida; Davis, Janet; Ucar, Didar; Fox, Austin; Chan, Chi Chao; Goldstein, Debra A.

2014-01-01

Ocular inflammatory disorders disproportionately affect women, and the majority of affected women are of childbearing age. The role of sex or reproductive hormones has been proposed in many other inflammatory or autoimmune disorders, and findings from non-ocular autoimmune diseases suggest a complex interaction between sex hormones, genetic factors and the immune system. However, despite the age and sex bias, factors that influence this disparity are complicated and unclear. This review aims to evaluate the gender disparities in prevalence, incidence and severity of the most common infectious and non-infectious ocular inflammatory disorders. PMID:24987987

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

PubMed

Bellone, Rebecca R

2017-12-01

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

Current concepts of ocular adnexal surgery

PubMed Central

Borrelli, Maria; Geerling, Gerd

2013-01-01

Ophthalmic Plastic and Reconstructive Surgery is a specialized area of ophthalmology that deals with the management of deformities and abnormalities of the eyelids, lacrimal system and the orbit. An ophthalmoplastic surgeon is able to identify and correct abnormalities of the ocular adnexae such as ectropion, lid retraction, conjunctival scarring with severe entropion, that can cause secondary ocular surface disorders; manage patients with watering eye, and when needed intervene with a dacryocystorhinostomy by external or endonasal approach and moreover minimize disfigurement following enucleation or evisceration and prevent further corneal damage, alleviate complains of tearing and grittiness, but also cosmetic complaints in patients with Graves’ orbitopathy. Aim of this manuscript was to review current established and recently evolving surgical procedures. PMID:26504698

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

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.

Clinical-Radiologic Correlation of Extraocular Eye Movement Disorders: Seeing beneath the Surface.

PubMed

Thatcher, Joshua; Chang, Yu-Ming; Chapman, Margaret N; Hovis, Keegan; Fujita, Akifumi; Sobel, Rachel; Sakai, Osamu

2016-01-01

Extraocular eye movement disorders are relatively common and may be a significant source of discomfort and morbidity for patients. The presence of restricted eye movement can be detected clinically with quick, easily performed, noninvasive maneuvers that assess medial, lateral, upward, and downward gaze. However, detecting the presence of ocular dysmotility may not be sufficient to pinpoint the exact cause of eye restriction. Imaging plays an important role in excluding, in some cases, and detecting, in others, a specific cause responsible for the clinical presentation. However, the radiologist should be aware that the imaging findings in many of these conditions when taken in isolation from the clinical history and symptoms are often nonspecific. Normal eye movements are directly controlled by the ocular motor cranial nerves (CN III, IV, and VI) in coordination with indirect input or sensory stimuli derived from other cranial nerves. Specific causes of ocular dysmotility can be localized to the cranial nerve nuclei in the brainstem, the cranial nerve pathways in the peripheral nervous system, and the extraocular muscles in the orbit, with disease at any of these sites manifesting clinically as an eye movement disorder. A thorough understanding of central nervous system anatomy, cranial nerve pathways, and orbital anatomy, as well as familiarity with patterns of eye movement restriction, are necessary for accurate detection of radiologic abnormalities that support a diagnostic source of the suspected extraocular movement disorder. © RSNA, 2016.

Should patients with ocular genetic disorders have genetic testing?

PubMed

Zanolli, Mario T; Khetan, Vikas; Dotan, Gad; Pizzi, Laura; Levin, Alex V

2014-09-01

To discuss the risks, benefits and value of genetic testing for ocular genetic disease. Testing for ocular genetics diseases is becoming more available and successful gene therapy is being reported. Clinicians must prepare for this trend by considering diagnostic genetic testing for their patients. As advances continually occur in genetic testing for ocular genetic disorders, clinicians must develop an understanding of the potential risks and benefits for their patients.

Influence of vision on masticatory muscles function: surface electromyographic evaluation

PubMed Central

Ciavarella, Domenico; Palazzo, Antonio; De Lillo, Alfredo; Lo Russo, Lucio; Paduano, Sergio; Laino, Luigi; Chimenti, Claudio; Frezza, Federica; Lo Muzio, Lorenzo

2014-01-01

Summary The role of the ocular disorders (OD) in pathogenesis of MMp is still a controversal issue. Ocular arc reflexes (OAR) may involve changes in head and neck posture and generate modifications of contraction resulting in muscle contraction and finally weakness. sEMG tests were performed on 28 patients (13 with masticatory muscles pain and myopia/15 healthy) in rest position with eyes open and eyes closed. Patients group control (healthy patients) showed no significance difference in sEMG record in open/close test. In non healthy patients there were great differences between the sEMG recordings with eyes closed and open. Temporalis and masseters showed a statistical difference of means activation in two tests (temporalis p = 0.0010; masseters = 0.0006). Great difference there was in means muscles activation between open eyes healthy test and non healthy. No difference in close eyes test was evaluated in temporalis and masseters close test in the two groups. The exact causes of MMp are still unknown. The role how ocular disorders (OD) may play an important role in pathogenesis of MMp is still a controversal issue. Ocular arc reflexes (OAR) may involve changes in head and neck posture and generate modifications of contraction resulting in muscle contraction and finally weakness. PMID:25002919

Oral Antibiotics for Meibomian Gland-Related Ocular Surface Disease: A Report by the American Academy of Ophthalmology.

PubMed

Wladis, Edward J; Bradley, Elizabeth A; Bilyk, Jurij R; Yen, Michael T; Mawn, Louise A

2016-03-01

To review the existing medical literature on the role of oral antibiotics in the management of ocular surface disease (OSD) that arises from disorders of the meibomian glands and to assess the efficacy of oral antibiotics in the management of this common ocular disease. A literature search was last conducted on August 12, 2015, in the PubMed and Cochrane databases for English-language original research investigations that evaluated the role of doxycycline, minocycline, and azithromycin in OSD among adult patients. The searches identified 87 articles, and 8 studies ultimately met the criteria outlined for this assessment. The 8 studies identified in the search documented an improvement in meibomian gland-related OSD after treatment with these agents, although side effects were common. This search identified only 1 randomized, controlled trial to assess the efficacy of these medications. Although oral antibiotics are used commonly in the management of OSD, there is no level I evidence to support their use. There are only a few studies that have assessed the efficacy of oral antibiotics in clinically meaningful ways in the management of OSD that arises from disorders of the meibomian glands. The current level of evidence is insufficient to conclude that antibiotics are useful in managing OSD arising from disorders of the meibomian glands. The few existing studies on the topic indicate that oral antibiotics may be an effective treatment for OSD that results from meibomian gland disease. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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.

Epidemiology of hereditary ocular disorders.

PubMed

Rosenberg, Thomas

2003-01-01

Molecular genetic evidence has contributed significantly to the understanding of the fundamental molecular biology of the eye in health and disease, but it has also exposed the inadequacy of our traditional clinically based classification of hereditary eye disorders by unravelling significant genetic non-allelic heterogeneity in many eye disorders. Furthermore, our understanding of the epidemiology of hereditary ocular disorders has gained considerably by the establishment of mutation spectra in a rapidly growing number of monogenic eye disorders. In this overview, special emphasis has been put on the growing impact of genetic eye diseases in visual impairment, genetic heterogeneity, and the role of founder mutations for the skewed appearance of certain hereditary ocular disorders in some populations.

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.

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.

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

Visual Dysfunction Following Blast-Related Traumatic Brain Injury from the Battlefield

DTIC Science & Technology

2010-10-27

sequelae follow- ing a TBI [12, 13]. The occurrence of TBI-related ocular and visual disorders is varied, depending on the diagnostic criteria...measure, ocular/visual disor- der, was indicated by the ICD-9-CM diagnostic codes for ‘disorders of the eye and adnexa’ (360.0– 379.9) obtained from...II. Number and percentage of US service members in each ocular/visual disorder diagnostic category by TBI status. ICD-9-CM code and categorya TBI (n

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.

Plasma rich in growth factors eye drops to treat secondary ocular surface disorders in patients with glaucoma

PubMed Central

Sánchez-Avila, Ronald M; Merayo-Lloves, Jesus; Fernández, Maria Laura; Rodríguez-Gutiérrez, Luis Alberto; Rodríguez-Calvo, Pedro Pablo; Fernández-Vega Cueto, Andres; Muruzabal, Francisco; Orive, Gorka; Anitua, Eduardo

2018-01-01

Purpose To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) eye drops in patients with glaucoma with secondary ocular surface disorders (OSDs) due to surgeries and topical hypotensive drugs use. Materials and methods A retrospective case-series study design was used including six patients (eight eyes) diagnosed with glaucoma who received surgical (nonpenetrating deep sclerectomy and/or trabeculectomy) and medical treatments (hypotensive eye drops) to control intraocular pressure (IOP) and who developed secondary OSDs, unresponsive to conventional treatments. Patients were treated with PRGF eye drops (four times a day). Outcome measures were ocular surface disease index (OSDI), best-corrected visual acuity (BCVA, in logarithm of the minimum angle of resolution), visual analog scale (VAS), frequency and severity of symptoms, and IOP. The safety of the treatment was also evaluated. Results Six patients (seven eyes with open-angle glaucoma and one eye with uveitic glaucoma) treated with PRGF eye drops were evaluated. Mean age was 71 years (SD=7.2, range 58–79 years). Five were female and one was male. The mean treatment time was 21.8 weeks (SD=9.0, range 12–36 weeks). The mean time to reach closure of the corneal ulcer was 14.5 (SD=5.5) weeks. A statistical significant reduction in OSDI scale (50.6%), VAS frequency (53.1%), VAS severity (42.0%), and a 41.8% improvement in BCVA were observed (p<0.05). IOP also decreased by 16.6% (p=0.010). Only one of the six patients reported itching in both eyes as an adverse event (AE); however, the patient continued with the PRGF eye drops until the end of therapy; the remaining patients did not report any AEs during the follow-up period. Conclusions In patients with glaucoma and secondary OSDs refractive to conventional treatments, the treatment with PRGF eye drops could be considered a possible therapeutic option, because it demonstrates an improvement in the signs and symptoms of the ocular surface, as well as a better control of the IOP. This is an initial research work that can open doors for future research to confirm these findings. PMID:29760570

Plasma rich in growth factors eye drops to treat secondary ocular surface disorders in patients with glaucoma.

PubMed

Sánchez-Avila, Ronald M; Merayo-Lloves, Jesus; Fernández, Maria Laura; Rodríguez-Gutiérrez, Luis Alberto; Rodríguez-Calvo, Pedro Pablo; Fernández-Vega Cueto, Andres; Muruzabal, Francisco; Orive, Gorka; Anitua, Eduardo

2018-01-01

To evaluate the efficacy and safety of plasma rich in growth factors (PRGF) eye drops in patients with glaucoma with secondary ocular surface disorders (OSDs) due to surgeries and topical hypotensive drugs use. A retrospective case-series study design was used including six patients (eight eyes) diagnosed with glaucoma who received surgical (nonpenetrating deep sclerectomy and/or trabeculectomy) and medical treatments (hypotensive eye drops) to control intraocular pressure (IOP) and who developed secondary OSDs, unresponsive to conventional treatments. Patients were treated with PRGF eye drops (four times a day). Outcome measures were ocular surface disease index (OSDI), best-corrected visual acuity (BCVA, in logarithm of the minimum angle of resolution), visual analog scale (VAS), frequency and severity of symptoms, and IOP. The safety of the treatment was also evaluated. Six patients (seven eyes with open-angle glaucoma and one eye with uveitic glaucoma) treated with PRGF eye drops were evaluated. Mean age was 71 years (SD=7.2, range 58-79 years). Five were female and one was male. The mean treatment time was 21.8 weeks (SD=9.0, range 12-36 weeks). The mean time to reach closure of the corneal ulcer was 14.5 (SD=5.5) weeks. A statistical significant reduction in OSDI scale (50.6%), VAS frequency (53.1%), VAS severity (42.0%), and a 41.8% improvement in BCVA were observed ( p <0.05). IOP also decreased by 16.6% ( p =0.010). Only one of the six patients reported itching in both eyes as an adverse event (AE); however, the patient continued with the PRGF eye drops until the end of therapy; the remaining patients did not report any AEs during the follow-up period. In patients with glaucoma and secondary OSDs refractive to conventional treatments, the treatment with PRGF eye drops could be considered a possible therapeutic option, because it demonstrates an improvement in the signs and symptoms of the ocular surface, as well as a better control of the IOP. This is an initial research work that can open doors for future research to confirm these findings.

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.

The eye as a window to rare endocrine disorders

PubMed Central

Chopra, Rupali; Chander, Ashish; Jacob, Jubbin J.

2012-01-01

The human eye, as an organ, can offer critical clues to the diagnosis of various systemic illnesses. Ocular changes are common in various endocrine disorders such as diabetes mellitus and Graves’ disease. However there exist a large number of lesser known endocrine disorders where ocular involvement is significant. Awareness of these associations is the first step in the diagnosis and management of these complex patients. The rare syndromes involving the pituitary hypothalamic axis with significant ocular involvement include Septo-optic dysplasia, Kallman's syndrome, and Empty Sella syndrome all affecting the optic nerve at the optic chiasa. The syndromes involving the thyroid and parathyroid glands that have ocular manifestations and are rare include Mc Cune Albright syndrome wherein optic nerve decompression may occur due to fibrous dysplasia, primary hyperparathyroidism that may present as red eye due to scleritis and Ascher syndrome wherein ptosis occurs. Allgrove's syndrome, Cushing's disease, and Addison's disease are the rare endocrine syndromes discussed involving the adrenals and eye. Ocular involvement is also seen in gonadal syndromes such as Bardet Biedl, Turner's, Rothmund's, and Klinefelter's syndrome. This review also highlights the ocular manifestation of miscellaneous syndromes such as Werner's, Cockayne's, Wolfram's, Kearns Sayre's, and Autoimmune polyendocrine syndrome. The knowledge of these relatively uncommon endocrine disorders and their ocular manifestations will help an endocrinologist reach a diagnosis and will alert an ophthalmologist to seek specialty consultation of an endocrinologist when encountered with such cases. PMID:22629495

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.

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

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

PubMed

Tashakori-Sabzevar, Faezeh; Mohajeri, Seyed Ahmad

2015-05-01

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

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

PubMed

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

1998-11-01

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

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

PubMed

Gagnon, Michael R; Dickinson, Paul J

2005-05-01

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

[Ocular findings in Polish Armed Forces in Iraq and Afghanistan, a review of medical examinations by The Military Medical Commission in Łodz].

PubMed

Pastuszka, Mirosław; Goś, Roman; Jurowski, Piotr; Chrzaszcz, Agnieszka; Smigielski, Janusz; Nowak, Michał S

2013-01-01

To determine the prevalence of ocular disorders among Polish soldiers returning from Iraq and Afghanistan military campaigns. A retrospective review of medical records of the Military Medical Commission of Lodz, Poland was performed. Records of 296 randomly selected soldiers, including 98 who returned from Iraq in 2004 and in 198 who returned from Afghanistan in 2012, were assessed. All subjects underwent comprehensive ocular examinations according to the military regulations. We used statistical analysis to review the results. The incidence of ocular disorders in Iraq and Afghanistan groups was 17.3% and 15.1%, respectively. The study revealed that the most common disorders among soldiers were refractive errors affecting 6.8% subjects, followed by defective color vision (4.7%) and solar retinopathy (3.0%). Combat injuries were diagnosed in 3 subjects, including 2 cases of corneal injury and 1 case of retinal detachment due to blast exposure. Combat injuries occurred in 1% of soldiers returning from Iraq and Afghanistan military campaigns. There were no statistically significant differences between Iraq and Afghanistan groups in the incidence of ocular disorders. Solar retinopathy was the most common problem related to the long-term exposure to rough climate conditions in both groups. ocular findings, Iraq, Afghanistan.

4A syndrome: ocular surface investigation in an Italian young patient.

PubMed

Aragona, Pasquale; Rania, Laura; Roszkowska, Anna Maria; Puzzolo, Domenico; Micali, Antonio; Pisani, Antonina; Salzano, Giuseppina; Messina, Maria Francesca

2014-12-08

Allgrove's 4A syndrome determines ocular surface changes. This is the first report providing an up-to-dated analysis of the ocular surface in an affected patient. An 18-years-old male Caucasian patient, with a complex progressive gait disorder and adrenal insufficiency, was referred for ophthalmic evaluation, as part of the clinical assessment. He underwent the following tests: best corrected visual acuity, tear osmolarity, tear film break-up time (BUT), corneal fluorescein staining, Schirmer's I test, lid margin assessment, corneal sensitivity, in vivo corneal confocal microscopy, conjunctival impression cytology, tonometry and fundus exam. A dry eye condition was documented by the Schirmer's I test of 0 mm/5' in both eyes, accompanied by tear hyperosmolarity, mild meibomian gland dysfunction, reduced BUT, mucus filaments in the tear film and conjunctival epithelium metaplasic changes. The corneal confocal microscopy showed the presence of activated keratocytes, while the nerve pattern was normal. The dry eye in this patient appears to be due to tear aqueous deficiency and can be considered as part of the 4A syndrome. The decreased tear production, resulting from a deterioration of the autonomic innervation of the lacrimal glands rather than an impaired corneal innervation, can be considered as part of the systemic autonomic dysfunction present in this disease.

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.

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

PubMed

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

2018-06-04

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

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

PubMed

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

2013-09-01

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

Autophagy mediates cell cycle response by regulating nucleocytoplasmic transport of PAX6 in limbal stem cells under ultraviolet-A stress

PubMed Central

Laggner, Maria; Pollreisz, Andreas; Schmidinger, Gerald; Schmidt-Erfurth, Ursula; Chen, Ying-Ting

2017-01-01

Limbal stem cells (LSC) account for homeostasis and regeneration of corneal epithelium. Solar ultraviolet A (UVA) is the major source causing oxidative damage in the ocular surface. Autophagy, a lysosomal degradation mechanism, is essential for physiologic function and stress defense of stem cells. PAX6, a master transcription factor governing corneal homeostasis by regulating cell cycle and cell fate of LSC, responds to oxidative stress by nucleocytoplasmic shuttling. Impaired autophagy and deregulated PAX6 have been reported in oxidative stress-related ocular surface disorders. We hypothesize a functional role for autophagy and PAX6 in LSC’s stress response to UVA. Therefore, human LSC colonies were irradiated with a sub-lethal dose of UVA and autophagic activity and intracellular reactive oxygen species (ROS) were measured by CYTO-ID assay and CM-H2DCFDA live staining, respectively. Following UVA irradiation, the percentage of autophagic cells significantly increased in LSC colonies while intracellular ROS levels remained unaffected. siRNA-mediated knockdown (KD) of ATG7 abolished UVA-induced autophagy and led to an excessive accumulation of ROS. Upon UVA exposure, LSCs displayed nuclear-to-cytoplasmic translocation of PAX6, while ATG7KD or antioxidant pretreatment largely attenuated the intracellular trafficking event. Immunofluorescence showing downregulation of proliferative marker PCNA and induction of cell cycle regulator p21 indicates cell cycle arrest in UVA-irradiated LSC. Abolishing autophagy, adenoviral-assisted restoration of nuclear PAX6 or antioxidant pretreatment abrogated the UVA-induced cell cycle arrest. Adenoviral expression of an ectopic PAX gene, PAX7, did not affect UVA cell cycle response. Furthermore, knocking down PAX6 attenuated the cell cycle progression of irradiated ATG7KD LSC by de-repressing p21 expression. Collectively, our data suggest a crosstalk between autophagy and PAX6 in regulating cell cycle response of ocular progenitors under UVA stress. Autophagy deficiency leads to impaired intracellular trafficking of PAX6, perturbed redox balance and uncurbed cell cycle progression in UVA-stressed LSCs. The coupling of autophagic machinery and PAX6 in cell cycle regulation represents an attractive therapeutic target for hyperproliferative ocular surface disorders associated with solar radiation. PMID:28700649

Dry eye symptoms align more closely to non-ocular conditions than to tear film parameters.

PubMed

Galor, Anat; Felix, Elizabeth R; Feuer, William; Shalabi, Nabeel; Martin, Eden R; Margolis, Todd P; Sarantopoulos, Constantine D; Levitt, Roy C

2015-08-01

To evaluate the relationship between dry eye symptoms, non-ocular conditions and tear film parameters. Cross-sectional study. The study population consisted of patients who were seen in the Miami Veterans Affairs eye clinic. Patients filled out standardised questionnaires assessing dry eye symptoms (dry eye questionnaire 5 (DEQ5) and ocular surface disease index (OSDI)), non-ocular pain, depression and post-traumatic stress disorder (PTSD), and also underwent measurement of tear film parameters. Correlations between dry eye symptoms and non-ocular conditions as compared with tear film parameters. 136 patients with a mean age of 65 (SD 11) years participated in the study. All correlations between the dry eye questionnaire scores (DEQ5 and OSDI) and (A) self-reported non-ocular pain measures (numerical rating scale and pain history), (B) depression and (C) PTSD were significant and moderate in strength (Pearson's coefficient 0.24 to 0.60, p<0.01 for all). All correlations between the dry eye questionnaires and tear film measures were weak (Pearson's coefficient -0.10 to 0.18) and most were not significant. Multivariable linear regression analyses revealed that PTSD and non-ocular pain more closely associated with dry eye symptoms than did tear film parameters. Specifically, non-ocular pain and PTSD accounted for approximately 36% of the variability in DEQ5 scores (R=0.60) and approximately 40% of variability in OSDI scores (R=0.64). Of note, none of the tear parameters remained significantly associated with dry eye symptoms in either model. Dry eye symptoms more closely align to non-ocular pain, depression and PTSD than to tear film parameters. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect of chronic exposure to welding light on Calabar welders.

PubMed

Davies, K G; Asanga, U; Nku, C O; Osim, E E

2007-01-01

It was generally observed that welders in Calabar, Nigeria did not always wear their protective goggles during welding. Since chronic exposure to welding light can impair vision this study was done to assess the effect of exposure to welding light on ocular function of welders in Calabar, Nigeria. There were 195 subjects comprising 110 welders (test) and 85 control subjects. Both groups were all male and had similar age range. The tests employed were clinical examination for ocular disorders, assessment of visual acuity, and opthalmoscopy. Test questionnaire was also used to record information on length of service, precautionary measures at work place, age and past ocular illnesses. The study also compared incidence of ocular disorders between the two groups of welders (arc and carbide welders). The mean ages of the welders and their control were not significantly different (27.53 +/- 10.0 vs 27.78 +/- 8.5 yrs respectively). There was a significantly [P < 0.01] higher incidence of pingueculum, cataract, allergic conjunctivitis, corneal opacity, and keratoconjunctivitis (arc eye) in welders than in their control subjects. However, visual acuity, incidence of pterygium and glaucoma were similar. Between the two groups of welders, the incidence of pterygium, corneal opacity and keratoconjunctivitis was significantly [P < 0.01] higher in arc welders than carbide welders. The incidence of pingueculum and glaucoma were however, similar. In conclusion, chronic exposure to welding light without adequate precaution may cause ocular disorders. Arc welding is more dangerous to ocular function than carbide welding. Length of service and age are predisposing factors to ocular disorders in the welding business.

Ocular Fixation Abnormality in Patients with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Shirama, Aya; Kanai, Chieko; Kato, Nobumasa; Kashino, Makio

2016-01-01

We examined the factors that influence ocular fixation control in adults with autism spectrum disorder (ASD) including sensory information, individuals' motor characteristics, and inhibitory control. The ASD group showed difficulty in maintaining fixation especially when there was no fixation target. The fixational eye movement characteristics of…

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.

Corneal thickness in dry eyes in an Iraqi population.

PubMed

Ali, Noora Mauwafak; Hamied, Furkaan M; Farhood, Qasim K

2017-01-01

Dry eye disorder is a multifactorial disease of the tears and ocular surface that results in discomfort and visual disturbance. Corneal pachymetry becomes increasingly important in refractive surgery, for the accurate assessment of intraocular pressure, and in the preoperative assessment of other ocular surgeries. To assess the effect of dry eye disorder on the central corneal thickness (CCT) by comparing with CCT of normal eyes of age-matched individuals. The total number of eyes examined was 280 (140 dry eyes from 70 patients and 140 normal eyes from 70 individuals). Pentacam (Scheimpflug imaging system) was used for measuring the CCT of all eyes. Patients with dry eye syndrome had significantly lower CCT compared to the control group ( P <0.01). Its mean was 536.5 versus 561.3, respectively. CCT of dry eyes was significantly reduced when compared with age- and gender-matched population. This result can be attributed to chronic desiccation by the inflammatory mediators in dry eyes, leading to corneal thinning.

Surveillance of Vision and Ocular Disorders in Children with Down Syndrome

ERIC Educational Resources Information Center

Stephen, Elma; Dickson, Jennifer; Kindley, A. David; Scott, Christopher C.; Charleton, Patricia M.

2007-01-01

Children with Down syndrome have a high prevalence of ocular disorders. The UK Down's Syndrome Medical Interest Group (DSMIG) guidelines for ophthalmic screening were locally implemented into a protocol that included neonatal eye examination by an opthalmologist and a comprehensive ophthalmological examination (cycloplegic refraction,…

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.

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

[Prevalence of neurological disorders among children with Down syndrome].

PubMed

Gaete, Beatriz; Mellado, Cecilia; Hernández, Marta

2012-02-01

Neurological disturbances are common problems in children with Down Syndrome (DS). To determine the prevalence of neurological disorders affecting children with Down Syndrome. Review of medical records of 253 children aged from 1 day to 23 years affected with DS, attended at a public hospital and a University clinic. The overall prevalence of neurological disorders was 38.7%. The most common problems were ocular motor disorders in 26% of cases and epilepsy in 12%. Neurological disorders are more common in children with DS than in the general population. Motor ocular disorders and epilepsy are the predominant disturbances detected.

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

[Study of ocular surface electromyography signal analysis].

PubMed

Zhu, Bei; Qi, Li-Ping

2009-11-01

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

[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.

Gait Balance Disorder by Thalamic Infarction with the Disorder of Interstitial Nucleus of Cajal

PubMed Central

Kurosu, A.; Hayashi, Y.; Wada, K.; Nagaoka, M.

2011-01-01

The interstitial nucleus of Cajal (INC) is thought to play an important role in torsional/vertical eye position and head posture, and disorders of the INC induce abnormal ocular movements and head tilt. Our patients with ocular tilt reactions simultaneously also had disturbances in ambulatory balance, yet no reports address the loss of balance control induced by disorders of the INC. We examined the ambulatory disturbances induced by INC lesion. We experienced three patients with ocular movement disorders and abnormal head tilt due to thalamic infarction. We performed ophthalmic examinations on and checked the balance of them. With funduscopy, abnormal cycloduction was seen in the unaffected side and normal cycloduction was observed in the affected side. Nevertheless, Hess charts showed distortions in the visual image of both eyes. They all had disorders of balance control. We tried to treat them using the Bobath approach for improving their ambulatory balance. With subsequent improvements in balance control it was possible for them to take short walks, but it was difficult to make any improvements in their ocular movement. The INC is related to balance control of ambulation and disorders of the INC induce ambulatory disturbances. Cycloduction was only observed in the unaffected side, but Hess charts showed distortions of the visual image in both eyes. Ambulation was briefly improved, but diplopia persisted in these patients. PMID:21769260

Corneal Mechanical Thresholds Negatively Associate With Dry Eye and Ocular Pain Symptoms.

PubMed

Spierer, Oriel; Felix, Elizabeth R; McClellan, Allison L; Parel, Jean Marie; Gonzalez, Alex; Feuer, William J; Sarantopoulos, Constantine D; Levitt, Roy C; Ehrmann, Klaus; Galor, Anat

2016-02-01

To examine associations between corneal mechanical thresholds and metrics of dry eye. This was a cross-sectional study of individuals seen in the Miami Veterans Affairs eye clinic. The evaluation consisted of questionnaires regarding dry eye symptoms and ocular pain, corneal mechanical detection and pain thresholds, and a comprehensive ocular surface examination. The main outcome measures were correlations between corneal thresholds and signs and symptoms of dry eye and ocular pain. A total of 129 subjects participated in the study (mean age 64 ± 10 years). Mechanical detection and pain thresholds on the cornea correlated with age (Spearman's ρ = 0.26, 0.23, respectively; both P < 0.05), implying decreased corneal sensitivity with age. Dry eye symptom severity scores and Neuropathic Pain Symptom Inventory (modified for the eye) scores negatively correlated with corneal detection and pain thresholds (range, r = -0.13 to -0.27, P < 0.05 for values between -0.18 and -0.27), suggesting increased corneal sensitivity in those with more severe ocular complaints. Ocular signs, on the other hand, correlated poorly and nonsignificantly with mechanical detection and pain thresholds on the cornea. A multivariable linear regression model found that both posttraumatic stress disorder (PTSD) score (β = 0.21, SE = 0.03) and corneal pain threshold (β = -0.03, SE = 0.01) were significantly associated with self-reported evoked eye pain (pain to wind, light, temperature) and explained approximately 32% of measurement variability (R = 0.57). Mechanical detection and pain thresholds measured on the cornea are correlated with dry eye symptoms and ocular pain. This suggests hypersensitivity within the corneal somatosensory pathways in patients with greater dry eye and ocular pain complaints.

Corneal Mechanical Thresholds Negatively Associate With Dry Eye and Ocular Pain Symptoms

PubMed Central

Spierer, Oriel; Felix, Elizabeth R.; McClellan, Allison L.; Parel, Jean Marie; Gonzalez, Alex; Feuer, William J.; Sarantopoulos, Constantine D.; Levitt, Roy C.; Ehrmann, Klaus; Galor, Anat

2016-01-01

Purpose To examine associations between corneal mechanical thresholds and metrics of dry eye. Methods This was a cross-sectional study of individuals seen in the Miami Veterans Affairs eye clinic. The evaluation consisted of questionnaires regarding dry eye symptoms and ocular pain, corneal mechanical detection and pain thresholds, and a comprehensive ocular surface examination. The main outcome measures were correlations between corneal thresholds and signs and symptoms of dry eye and ocular pain. Results A total of 129 subjects participated in the study (mean age 64 ± 10 years). Mechanical detection and pain thresholds on the cornea correlated with age (Spearman's ρ = 0.26, 0.23, respectively; both P < 0.05), implying decreased corneal sensitivity with age. Dry eye symptom severity scores and Neuropathic Pain Symptom Inventory (modified for the eye) scores negatively correlated with corneal detection and pain thresholds (range, r = −0.13 to −0.27, P < 0.05 for values between −0.18 and −0.27), suggesting increased corneal sensitivity in those with more severe ocular complaints. Ocular signs, on the other hand, correlated poorly and nonsignificantly with mechanical detection and pain thresholds on the cornea. A multivariable linear regression model found that both posttraumatic stress disorder (PTSD) score (β = 0.21, SE = 0.03) and corneal pain threshold (β = −0.03, SE = 0.01) were significantly associated with self-reported evoked eye pain (pain to wind, light, temperature) and explained approximately 32% of measurement variability (R = 0.57). Conclusions Mechanical detection and pain thresholds measured on the cornea are correlated with dry eye symptoms and ocular pain. This suggests hypersensitivity within the corneal somatosensory pathways in patients with greater dry eye and ocular pain complaints. PMID:26886896

Therapeutic potential of trichostatin A to control inflammatory and fibrogenic disorders of the ocular surface.

PubMed

Kitano, Ai; Okada, Yuka; Yamanka, Osamu; Shirai, Kumi; Mohan, Rajiv R; Saika, Shizuya

2010-12-31

To examine the effects of a histone deacetylase inhibitor, Trichostatin A (TSA), on the behavior of macrophages and subconjunctival fibroblasts in vitro and on ocular surface inflammation and scarring in vivo using an alkali burn wound healing model. Effects of TSA on expression of inflammation-related growth factors or collagen I were examined by real-time RT-PCR or immunoassay in mouse macrophages or human subconjunctival fibroblasts. Effects of TSA on trans forming growth factor β (TGFβ)/Smad signaling were evaluated with western blotting and/or immunocytochemistry. Alkali-burn injuries on the eyes of mice were performed with three µl of 0.5 N NaOH under general and topical anesthesia. TSA (600 µg/Kg daily) or vehicle was administered to animals via intraperitoneal (i.p.) injection. Histology and real-time RT-PCR investigations evaluated the effects of TSA on the healing process of the cornea. TSA inhibited TGFβ 1 and vascular endothelial growth factor (VEGF) expression in macrophages, and TGFβ1 and collagen I in ocular fibroblasts. It elevated the expression of 5'-TG-3'-interacting factor (TGIF) and Smad7 in fibroblasts and blocked nuclear translocation of phospho-Smad2. Real-time PCR and immunocytochemistry studies showed that systemic administration of TSA suppressed the inflammation and fibrotic response in the stroma and accelerated epithelial healing in the alkali-burned mouse cornea. Systemic administration of TSA reduces inflammatory and fibrotic responses in the alkali-burned mouse ocular surface in vivo. The mechanisms of action involve attenuation of Smad signal in mesenchymal cells and reduction in the activation and recruitment of macrophages. TSA has the potential to treat corneal scarring in vivo.

Correlation between vestibulo-ocular reflex and optokinetic afternystagmus in normal subjects and in patients with vestibular system disorders

PubMed Central

Dellepiane, M; Medicina, MC; Barettini, L; Mura, AC

2006-01-01

Summary Optokinetic afternystagmus follows optokinetic nystagmus as an expression of the central velocity storage integrator discharge and its fast phase is beating in the same direction as the previous optokinetic nystagmus. We investigated the correlation between vestibulo-ocular reflex and optokinetic afternystagmus in normal subjects and in patients with bilateral vestibular disorders. The aim of this study was to determine the possible role of optokinetic afternystagmus as a diagnostic test for identifying functional vestibular disorders. The subjects were examined by electronystagmography and vestibulo-ocular reflex, optokinetic nystagmus stare type as well as optokinetic afternystagmus were recorded. They were restrained in a rotatory drum chair, both the chair and the drum could be rotated, independently or coupled. For vestibulo-ocular reflex analysis, we studied post-rotatory-nystagmus from a velocity of 90°s. Optokinetic nystagmus was recorded at a drum velocity of 30°s and the registration continued in total darkness, after the illumination was switched off, to study optokinetic afternystagmus. We considered vestibulo-ocular reflex and optokinetic nystagmus gain, vestibulo-ocular reflex and optokinetic afternystagmus constant of time (tc) defined as the time necessary for the slow phase eye velocity to be reduced to 37% of its initial value. Results demonstrated that vestibulo-ocular reflex gain and ct showed a significant difference only in patients with reduced vestibular reflexia, while optokinetic nystagmus gain was greater only in patients with increased reflexia; optokinetic afternystagmus ct was different from the control group only in patients with hyporeflexia. In conclusion, our results suggest that vestibulo-ocular reflex and optokinetic afternystagmus ct are clinically more useful than the gain alone in testing vestibular disorders with hyporeflexia. On the other hand, we propose a new mathematical and statistical approach to study the temporal evolution of more parameters of the nystagmus. PMID:18383753

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.

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

PubMed

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

2014-12-05

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

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

PubMed

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

2014-12-01

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

[Ocular disturbances in neuromuscular disorders].

PubMed

Pénisson-Besnier, I; Lamirel, C

2008-11-01

Compared with other skeletal muscles, extraocular muscles have fundamentally distinct properties that make them selectively vulnerable to certain neuromuscular disorders. When the oculomotor signs are predominant, their temporal progression allows the clinician to make the distinction between a muscular disease (mitochondrial disorder, oculopharyngeal muscular dystrophy...) and a disorder of the neuromuscular junction (myasthenia gravis, botulism...). In other instances, such as myotonic dystrophy or facioscapulohumeral dystrophy, the ocular signs are not in the forefront but must be recognized by the ophthalmologist as hallmarks of a muscular disorder. In all cases, the collaboration between the neurologist and the ophthalmologist is fruitful.

Visual Behaviors and Adaptations Associated with Cortical and Ocular Impairment in Children.

ERIC Educational Resources Information Center

Jan, J. E.; Groenveld, M.

1993-01-01

This article shows the usefulness of understanding visual behaviors in the diagnosis of various types of visual impairments that are due to ocular and cortical disorders. Behaviors discussed include nystagmus, ocular motor dyspraxia, head position, close viewing, field loss adaptations, mannerisms, photophobia, and abnormal color perception. (JDD)

A trend toward smaller optical angles and medial-ocular distance in schizophrenia spectrum, but not in bipolar and major depressive disorders.

PubMed

Wang, Yi; Deng, Yi; Li, Zhi; Li, Xu; Zhang, Chen-Yuan; Jin, Zhen; Fan, Ming-Xia; Compton, Michael T; Cheung, Eric F C; Lim, Kelvin O; Chan, Raymond C K

2016-12-01

Minor physical anomalies (MPAs) are subtle signs of fetal developmental abnormalities that have been considered to be among the most replicated risk markers for schizophrenia-spectrum disorders. However, quantitative approaches are needed to measure craniofacial MPAs. The present study adopted an imaging-based quantitative approach to examine craniofacial MPAs across the spectrum of schizophrenia and affective disorders, to address their sensitivity and specificity. We sampled 31 patients with schizophrenia, 30 of their unaffected relatives, and 30 individuals with schizotypal personality traits, as well as 37 non-schizotypal controls. We also examined 17 patients with bipolar disorder and 19 patients with major depressive disorder. Five craniofacial MPAs were measured on anterior-posterior commissure-aligned T1-weighted images of an individual's native brain space: medial-ocular distance, lateral-ocular distance, optical angle, maximum skull length, and skull-base width. Compared to non-schizotypal controls, patients with schizophrenia and their relatives showed a trend toward having smaller optical angles and medial-ocular distance, while no difference was found in patients with bipolar or major depressive disorders, suggesting some degree of specificity to schizophrenia. Our approach may benefit future research on craniofacial MPAs as risk markers for schizophrenia-spectrum disorders, and may eventually be useful in strategies to enhance risk stratification using multiple risk markers. © 2016 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

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

A reinterpretation of certain disorders affecting the eye muscles and their tissues

PubMed Central

Poonyathalang, Anuchit; Khanna, Sangeeta; Leigh, R John

2007-01-01

Recent discoveries about the orbital tissues prompt a re-evaluation of the way that clinicians think about disorders affecting the extraocular muscles, their nerves and motoneurons in the brainstem. The revolutionary discovery that the orbital layers of the extraocular muscles insert not onto the eyeball, but into fibromuscular pulleys that guide the orbital layers, provides explanations for the kinematic properties of eye rotations and clinical findings in some patients with strabismus. The demonstration that all extraocular fibers types, except pale global fibers, lack synaptic folding provides an explanation for why saccades may remain fast in patients with limited ocular mobility due to myasthenia gravis. More than one mechanism may account for the observation that patients with disorders affecting the eye muscles or their nerves can present with the appearance of central disorders of ocular motility, such as internuclear ophthalmoplegia. New approaches to analyzing saccades in patients with disjunctive eye movements provide the means to identify disorders affecting the peripheral or central components of the ocular motor system, or both. PMID:19668518

Ocular Findings in Children With 22q11.2 Deletion Syndrome.

PubMed

Gokturk, Bahar; Topcu-Yilmaz, Pinar; Bozkurt, Banu; Yildirim, Mahmut Selman; Guner, Sukru Nail; Sayar, Esra Hazar; Reisli, Ismail

2016-07-01

To identify the ocular features of children diagnosed as having 22q11.2 deletion syndrome in a Turkish population, which is the most common microdeletion syndrome with a wide range of facial and ocular abnormalities. Sixteen children aged between 4 months and 18 years with a microdeletion in chromosome 22q11.2 underwent a detailed ophthalmological examination including uncorrected and best corrected visual acuity testing, stereoscopic vision examination, biomicroscopic and indirect fundus examination, and ocular motility testing. All patients had at least one ocular abnormality. The major abnormalities were eyelid abnormalities (eye hooding, narrow palpebral fissure, telecanthus, hypertelorism, sparse and thin eyebrows and eyelashes, blepharitis, and distichiasis), posterior embryotoxon, and tortuous retinal vessels in at least half of the patients. Other ophthalmological disorders were refractive errors, iris remnants, and strabismus. The chromosome 22q11.2 deletion syndrome is associated with a wide range of ocular disorders, which necessitates a comprehensive eye examination for appropriate treatment and follow-up. Ocular findings sometimes can provide a clue to the diagnosis of 22q11.2 deletion. [J Pediatr Ophthalmol Strabismus. 2016;53(4):218-222]. Copyright 2016, SLACK Incorporated.

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.

Molecular genetics of inherited eye disorders.

PubMed

MacDonald, I M; Sasi, R

1994-10-01

In the past 10 y, there have been considerable advances in the mapping, isolation, and characterization of many genes for important ocular conditions: retinitis pigmentosa, Norrie disease, Waardenburg syndrome, choroideremia, aniridia, retinoblastoma, and others. The candidate gene approach has now supplemented classical linkage studies and positional cloning in the investigation of ocular disorders. Developmentally expressed genes and animal models have provided insights as to the etiology of other disorders. With this knowledge at hand, genetic counselling for heritable eye diseases has been greatly improved.

Ocular Applications of Dipyridamole: A Review of Indications and Routes of Administration

PubMed Central

Isakov, Itzhak; Wlassoff, Wjatschesslaw; Ingram, April; Barishak, Y. Robert

2016-01-01

Abstract Dipyridamole was introduced decades ago as a treatment for angina, subsequently found to inhibit platelet aggregation. It is most commonly used, and approved for use in thromboembolism prevention, following surgery. Some of its recognized effects such as adenosine uptake inhibition, elevation of cAMP and cGMP levels, vasodilation, and tissue perfusion are important in various ocular disorders. For this reason, dipyridamole represents an interesting candidate as a therapeutic target for the treatment of eye disorders affecting different ocular structures. The aim of this article is to review the evidence and current understanding of the mechanisms by which dipyridamole exerts its effects on different ocular tissues, discuss the role of dipyridamole in clinical practice, and highlight areas of use and routes of administration. PMID:26696547

Tear Film Steroid Profiling in Dry Eye Disease by Liquid Chromatography Tandem Mass Spectrometry

PubMed Central

Agnifili, Luca; Cicalini, Ilaria; Calienno, Roberta; Zucchelli, Mirco; Mastropasqua, Leonardo; Sacchetta, Paolo; Del Boccio, Piero; Rossi, Claudia

2017-01-01

Dry eye disease (DED) is a multifactorial disorder of the ocular surface unit resulting in eye discomfort, visual disturbance, and ocular surface damage; the risk of DED increases with age in both sexes, while its incidence is higher among females caused by an overall hormonal imbalance. The role of androgens has recently investigated and these hormones were considered to have a protective function on the ocular surface. In order to correlate DED to tear steroid levels, a robust, specific, and selective method for the simultaneous quantification of cortisol (CORT), corticosterone (CCONE), 11-deoxycortisol (11-DECOL), 4-androstene-3,17-dione (ADIONE), testosterone (TESTO), 17α-hydroxyprogesterone (17-OHP), and progesterone (PROG) was developed and applied for the analysis of tear samples. The method involves a simple extraction procedure of steroids from tears collected on Schirmer strips, followed by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. In total, tear samples from 14 DED female patients and 13 healthy female controls were analysed and, CORT, ADIONE, and 17-OHP response levels resulted significantly decreased in dry eye patients respect to controls. The receiver operating characteristic (ROC) curve obtained by the combination of these three steroids (AUC = 0.964) demonstrated the good diagnostic power of the differential tear steroids in identifying DED. In conclusion, the present method made it possible, for the first time, to study steroid profiling directly in tear fluid. PMID:28672794

Bipolar Disorder With Psychotic Features and Ocular Toxoplasmosis: A Possible Pathogenetic Role of the Parasite?

PubMed

Del Grande, Claudia; Contini, Carlo; Schiavi, Elisa; Rutigliano, Grazia; Maritati, Martina; Seraceni, Silva; Pinto, Barbara; Dell'Osso, Liliana; Bruschi, Fabrizio

2017-03-01

Recent evidence suggests the involvement of Toxoplasma gondii infection in the emergence of psychotic and affective disorders. In this report, we describe the case of a young Brazilian woman affected by recurrent ocular toxoplasmosis and presenting with a manic episode with psychotic features in the context of a diagnosis of Bipolar Disorder (BD), type I. We observed a relationship between ocular manifestations and the clinical course of bipolar illness, confirmed by molecular analyses (nested-PCR), as well as by the high level of T. gondii specific IgG. This case report is the first showing the presence of circulating parasite DNA at the time of occurrence of psychiatric symptoms, thus providing further support for a possible role of the parasite in the pathogenesis of some cases of BD.

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

Thiolated nanostructured lipid carriers as a potential ocular drug delivery system for cyclosporine A: Improving in vivo ocular distribution.

PubMed

Shen, Jie; Deng, Yanping; Jin, Xuefeng; Ping, Qineng; Su, Zhigui; Li, Lejun

2010-12-15

Ophthalmic drug delivery with long pre-corneal retention time and high penetration into aqueous humor and intraocular tissues is the key-limiting factor for the treatment of ocular diseases and disorders. Within this study, the conjugate of cysteine-polyethylene glycol monostearate (Cys-PEG-SA) was synthesized and was used to compose the thiolated nanostructured lipid carrier (Cys-NLC) as a potential nanocarrier for the topical ocular administration of cyclosporine A (CyA). The rapid cross-linking process of Cys-PEG-SA in vitro was found in simulated physiological environment. The in vitro CyA release from Cys-NLC was slower than that of non-thiolated nanostructured lipid carriers (NLC) due to the cross-linking of thiomers on the surface of nanocarriers. After topical ocular administration in rabbits, the in vivo ocular distribution of CyA was investigated in comparison of Cys-NLC with non-thiolated NLCs and oil solution. The results showed that CyA concentration in systemic blood was very low and close to the detection limit. The area-under-the-curve (AUC(0-24h)) and mean retention time (MRT(0-24h)) of Cys-NLC group in aqueous humor, tear and eye tissues were significantly higher than that of oil solution, non-thiolated NLCs (p<0.05). These results demonstrated that the thiolated NLC could deliver high level of CyA into intraocular tissues due to its bioadhesive property and sustained release characteristics. Copyright © 2010 Elsevier B.V. All rights reserved.

We are not alone: a case for the human microbiome in extra intestinal diseases.

PubMed

Shivaji, S

2017-01-01

"Dysbiosis" in the gut microbiome has been implicated in auto-immune diseases, in inflammatory diseases, in some cancers and mental disorders. The challenge is to unravel the cellular and molecular basis of dysbiosis so as to understand the disease manifestation. Next generation sequencing and genome enabled technologies have led to the establishment of the composition of gut microbiomes and established that "dysbiosis" is the cause of several diseases. In a few cases the cellular and molecular changes accompanying dysbiosis have been investigated and correlated with the disease. Gut microbiome studies have indicated that Christensenella minuta controls obesity in mice, Faecalibacterium prausnitzii protects mice against intestinal inflammation and Akkermansia muciniphila reverses obesity and insulin resistance by secreting endocannabinoids. In mice polysaccharide antigen A on the surface of Bacteroides fragilis , reduces inflammation. Such experiments provide the link between the gut microbiome and human health but implicating dysbiosis with extra-intestinal diseases like arthritis, muscular dystrophy, vaginosis, fibromyalgia, some cancers and mental disorders appears to be more challenging. The relevance of gut microbiome to the eye appears to be very remote. But considering that the eye is the site of inflammatory diseases like uveitis, scleritis, Mooren's corneal ulcer etc. it is possible that these diseases are also influenced by dysbiosis. In mice signals from the gut microbiota activate retina specific T cells that are involved in autoimmune uveitis. Such information would open up new strategies for therapy where the emphasis would be on restoring the diversity in the gut by antibiotic or specific drug use, specific microbe introduction, probiotic use and fecal transplant therapy. The ocular surface microbiome may also be responsible for eye diseases in man but such studies are lacking. Microbiome of the healthy cornea and conjunctiva have been identified. But whether the ocular microbiome exhibits dysbiosis with disease? Whether ocular microbiome is influenced by the gut microbiome? What mediates the cross-talk between the gut and ocular microbiomes? These are questions that need to be addressed to understand idiopathic infections of the eye. Evaluating diseases remote from the gut would unfold the mysteries of the microbiome.

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2006-01-01

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

Ophthalmic manifestations in patients with ectodermal dysplasia syndromes.

PubMed

Keklikci, Ugur; Yavuz, Izzet; Tunik, Selcuk; Ulku, Zelal Baskan; Akdeniz, Sedat

2014-01-01

Ectodermal dysplasia (ED) is a disorder that results from abnormal formation of at least two of the four major ectodermal derivatives in the developing embryo. The ectoderm of the embryo forms the skin, teeth, hair and nails, sweat glands and part of the eyes. The aim of this article is to reveal ophthalmologic symptoms and signs as multidisciplinary, reliable criteria for ectodermal dysplasia. In this retrospective study, 24 patients with ED were analyzed from the recorded data. Ophthalmological examination of the patients, who had previously received the diagnosis of ED in the dental department, was done. During the examination, ocular symptoms related to tear film, corneal changes, lacrimal duct, periorbital hyperpigmentation, alteration lashes and eyebrows were evaluated. The age ranged between 3-45, and the mean and standard deviation (Mean ± SD) was 15.8 ± 7.4 years. The number of males was 13 (54.2%) and females, 11 (45.8%). Eighteen patients (75.0%) suffered from ocular complaints related to the ocular surface. In 11 of the patients with ED, there were dry eye symptoms. While the mean age of cases with eye involvement was 17.5, it was 23.1 in cases with dry eye symptoms. In the study, it was observed that, in patients with ED, ocular complaints, particularly dry eye symptoms, may increase as age advances.

Intracellular trafficking of hyaluronic acid-chitosan oligomer-based nanoparticles in cultured human ocular surface cells.

PubMed

Contreras-Ruiz, Laura; de la Fuente, María; Párraga, Jenny E; López-García, Antonio; Fernández, Itziar; Seijo, Begoña; Sánchez, Alejandro; Calonge, Margarita; Diebold, Yolanda

2011-01-27

Nanoparticles are a promising alternative for ocular drug delivery, and our group has proposed that they are especially suited for ocular mucosal disorders. The goal of the present study was to determine which internalization pathway is used by cornea-derived and conjunctiva-derived cell lines to take up hyaluronic acid (HA)-chitosan oligomer (CSO)-based nanoparticles (HA-CSO NPs). We also determined if plasmids loaded onto the NPs reached the cell nucleus. HA-CSO NPs were made of fluoresceinamine labeled HA and CSO by ionotropic gelation and were conjugated with a model plasmid DNA for secreted alkaline phosphatase. Human epithelial cell lines derived from the conjunctiva and the cornea were exposed to HA-CSO NPs for 1 h and the uptake was investigated in living cells by fluorescence microscopy. The influence of temperature and metabolic inhibition, the effect of blocking hyaluronan receptors, and the inhibition of main endocytic pathways were studied by fluorometry. Additionally, the metabolic pathways implicated in the degradation of HA-CSO NPs were evaluated by lysosome identification. There was intracellular localization of plasmid-loaded HACSO NPs in both corneal and conjunctival cells. The intracellular presence of NPs diminished with time. HA-CSO NP uptake was significantly reduced by inhibition of active transport at 4 °C and by sodium azide. Uptake was also inhibited by blocking hyaluronan receptors with anti-CD44 Hermes-1 antibody, by excess HA, and by filipin, an inhibitor of caveolin-dependent endocytosis. HA-CSO NPs had no effect on cell viability. The transfection efficiency of the model plasmid was significantly higher in NP treated cells than in controls. HA-CSO NPs were internalized by two different ocular surface cell lines by an active transport mechanism. The uptake was mediated by hyaluronan receptors through a caveolin-dependent endocytic pathway, yielding remarkable transfection efficiency. Most of HA-CSO NPs were metabolized within 48 h. This uptake did not compromise cell viability. These findings further support the potential use of HA-CSO NPs to deliver genetic material to the ocular surface.

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

PubMed

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

2017-06-01

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

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

PubMed

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

2003-03-01

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

Motion Detection in the Far Peripheral Vision Field

DTIC Science & Technology

2007-12-01

perimetry, SITA. Acta Ophthalmol 1997 , 75, 368-375. 43. Turpin , A.; McKendrick, A. M.; Johnson, C. A.; Vingrys, A. J. Properties of perimetric threshold...be a valuable clinical ophthalmic tool for early detection and differential diagnosis of ocular and neurologic disorders (11 through 17... differential diagnosis of ocular and neurologic disorders (11, 12, 14 through 17, 47). The purpose of the present investigation is to determine the feasibility

[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.

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.

UV-blocking spectacle lens protects against UV-induced decline of visual performance.

PubMed

Liou, Jyh-Cheng; Teng, Mei-Ching; Tsai, Yun-Shan; Lin, En-Chieh; Chen, Bo-Yie

2015-01-01

Excessive exposure to sunlight may be a risk factor for ocular diseases and reduced visual performance. This study was designed to examine the ability of an ultraviolet (UV)-blocking spectacle lens to prevent visual acuity decline and ocular surface disorders in a mouse model of UVB-induced photokeratitis. Mice were divided into 4 groups (10 mice per group): (1) a blank control group (no exposure to UV radiation), (2) a UVB/no lens group (mice exposed to UVB rays, but without lens protection), (3) a UVB/UV400 group (mice exposed to UVB rays and protected using the CR-39™ spectacle lens [UV400 coating]), and (4) a UVB/photochromic group (mice exposed to UVB rays and protected using the CR-39™ spectacle lens [photochromic coating]). We investigated UVB-induced changes in visual acuity and in corneal smoothness, opacity, and lissamine green staining. We also evaluated the correlation between visual acuity decline and changes to the corneal surface parameters. Tissue sections were prepared and stained immunohistochemically to evaluate the structural integrity of the cornea and conjunctiva. In blank controls, the cornea remained undamaged, whereas in UVB-exposed mice, the corneal surface was disrupted; this disruption significantly correlated with a concomitant decline in visual acuity. Both the UVB/UV400 and UVB/photochromic groups had sharper visual acuity and a healthier corneal surface than the UVB/no lens group. Eyes in both protected groups also showed better corneal and conjunctival structural integrity than unprotected eyes. Furthermore, there were fewer apoptotic cells and less polymorphonuclear leukocyte infiltration in corneas protected by the spectacle lenses. The model established herein reliably determines the protective effect of UV-blocking ophthalmic biomaterials, because the in vivo protection against UV-induced ocular damage and visual acuity decline was easily defined.

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

PubMed

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

2018-06-28

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

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2017-11-01

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

Ocular findings among young men: a 12-year prevalence study of military service in Poland.

PubMed

Nowak, Michal S; Jurowski, Piotr; Gos, Roman; Smigielski, Janusz

2010-08-01

To determine the prevalence of ocular diseases among young men and to assess the main ocular causes reflecting discharge from military service in Poland. A retrospective review of the medical records of 105 017 men undergoing a preliminary examination for military service during the period 1993-2004. Sample size for the study was calculated with 99% confidence within an error margin of 5%. All of the study participants were White men of European origin, most of whom live or lived in Poland. Data regarding the vision status were assessed in 1938 eyes of 969 participants. Two groups were distinguished based on the age of the participants: group I aged 18-24 years, and group II aged 25-34 years. Presented visual impairment [visual acuity (VA)<20/40)] followed by colour vision defects were the most common ocular disorders, accounting for 13.2%. There were statistically significant differences in uncorrected VA as well as in the rates of particular refractive errors in between the age groups (p<0.05). The prevalence of glaucoma and ocular hypertension was significantly higher in older participants. Six hundred and sixty-seven (68.8%) participants examined medically in the study period were accepted for military service. However, 302 (31.2%) failed their examination and were temporarily or permanently discharged from duty. Fifty-two of them (17.2%) were discharged because of various ocular disorders. The most common causes were high refractive errors, which accounted for 38.5% of all the ocular discharges, followed by chronic and recurrent diseases of the posterior segment of the eye, which accounted for 19.2%. The prevalence of ocular disorders among young men in an unselected military population was closer to the results obtained in other population-based studies comprising both men and women in the same age group. High refractive errors followed by chronic and recurrent diseases of the posterior segment of the eye are important causes of medical discharges from military service in Poland.

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.

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

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.

Noninvasive Dry Eye Assessment Using High-Technology Ophthalmic Examination Devices.

PubMed

Yamaguchi, Masahiko; Sakane, Yuri; Kamao, Tomoyuki; Zheng, Xiaodong; Goto, Tomoko; Shiraishi, Atsushi; Ohashi, Yuichi

2016-11-01

Recently, the number of dry eye cases has dramatically increased. Thus, it is important that easy screening, exact diagnoses, and suitable treatments be available. We developed 3 original and noninvasive assessments for this disorder. First, a DR-1 dry eye monitor was used to determine the tear meniscus height quantitatively by capturing a tear meniscus digital image that was analyzed by Meniscus Processor software. The DR-1 meniscus height value significantly correlated with the fluorescein meniscus height (r = 0.06, Bland-Altman analysis). At a cutoff value of 0.22 mm, sensitivity of the dry eye diagnosis was 84.1% with 90.9% specificity. Second, the Tear Stability Analysis System was used to quantitatively measure tear film stability using a topographic modeling system corneal shape analysis device. Tear film stability was objectively and quantitatively evaluated every second during sustained eye openings. The Tear Stability Analysis System is currently installed in an RT-7000 autorefractometer and topographer to automate the diagnosis of dry eye. Third, the Ocular Surface Thermographer uses ophthalmic thermography for diagnosis. The decrease in ocular surface temperature in dry eyes was significantly greater than that in normal eyes (P < 0.001) at 10 seconds after eye opening. Decreased corneal temperature correlated significantly with the tear film breakup time (r = 0.572; P < 0.001). When changes in the ocular surface temperature of the cornea were used as indicators for dry eye, sensitivity was 0.83 and specificity was 0.80 after 10 seconds. This article describes the details and potential of these 3 noninvasive dry eye assessment systems.

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

Changes in ocular higher-order aberrations following botulinum toxin treatment in patients with blepharospasm : BTX improves dry eye in patients with BEB.

PubMed

Isshiki, Yoshihiko; Ishikawa, Hiroto; Mimura, Osamu

2016-11-01

To evaluate the effects of botulinum toxin type A (BTX-A) treatment in patients with benign essential blepharospasm (BEB) by monitoring the ocular surface and ocular higher-order aberrations (HOAs) before and after treatment. The present study reports a prospective case series of 38 patients (76 eyes, 11 men and 27 women; mean age 66.8 ± 9.8 years) with BEB who underwent BTX-A treatment at Kokura Memorial Hospital between 2013 and 2014. Patients were evaluated for ophthalmoscopic findings, Schirmer I test, tear film break-up time (t-BUT), HOAs, fluctuation index (FI), stability index (SI) using a wavefront aberrometer, 15 subjective symptoms using the Dry Eye-Related Quality of Life Score (DEQS), and complications before and after the treatment. After BTX-A treatment, the Schirmer I test score improved significantly from 5.9 ± 5.4 to 8.7 ± 6.1 mm and t-BUT recovered from 5.2 ± 1.7 to 7.3 ± 1.7 s. HOAs were classified into four patterns: stable (60.5 %), small fluctuation (14.5 %), sawtooth (17.1 %), and reverse sawtooth (7.9 %), and they significantly reduced after the treatment. Only FI (not SI) showed a marked reduction, and the DEQS significantly improved from 44.7 ± 21.6 to 37.6 ± 21.0 after the treatment (p < 0.05). There were no complications during the observations. BTX-A is a treatment with a high potential to improve ocular surface disorders induced by BEB.

Corneal endothelial dysfunction in Pearson syndrome.

PubMed

Kasbekar, Shivani A; Gonzalez-Martin, Jose A; Shafiq, Ayad E; Chandna, Arvind; Willoughby, Colin E

2013-01-01

Mitochondrial disorders are associated with well recognized ocular manifestations. Pearson syndrome is an often fatal, multisystem, mitochondrial disorder that causes variable bone marrow, hepatic, renal and pancreatic exocrine dysfunction. Phenotypic progression of ocular disease in a 12-year-old male with Pearson syndrome is described. This case illustrates phenotypic drift from Pearson syndrome to Kearns-Sayre syndrome given the patient's longevity. Persistent corneal endothelial failure was noted in addition to ptosis, chronic external ophthalmoplegia and mid-peripheral pigmentary retinopathy. We propose that corneal edema resulting from corneal endothelial metabolic pump failure occurs within a spectrum of mitochondrial disorders.

Ocular manifestations of drug and alcohol abuse

PubMed Central

Peragallo, Jason; Biousse, Valérie; Newman, Nancy J.

2015-01-01

Purpose of review To review commonly encountered adverse ocular effects of illicit drug use. Recent findings Drug and alcohol abuse can produce a variety of ocular and neuro-ophthalmic side effects. Novel, so-called “designer,” drugs of abuse can lead to unusual ocular disorders. Legal substances, when used in manners for which they have not been prescribed, can also have devastating ophthalmic consequences. Summary In this review we will systematically evaluate each part of the visual pathways and discuss how individual drugs may affect them. PMID:24100364

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.

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.

Ocular diseases: immunological and molecular mechanisms

PubMed Central

Song, Jing; Huang, Yi-Fei; Zhang, Wen-Jing; Chen, Xiao-Fei; Guo, Yu-Mian

2016-01-01

Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation. PMID:27275439

Ocular diseases: immunological and molecular mechanisms.

PubMed

Song, Jing; Huang, Yi-Fei; Zhang, Wen-Jing; Chen, Xiao-Fei; Guo, Yu-Mian

2016-01-01

Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation.

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.

Minor Salivary Gland Transplantation for Severe Dry Eyes.

PubMed

Wakamatsu, Tais Hitomi; SantʼAnna, Ana Estela Besteti Pires Ponce; Cristovam, Priscila Cardoso; Alves, Venâncio Avancini Ferreira; Wakamatsu, Alda; Gomes, José Alvaro Pereira

2017-11-01

Dry eye is a multifactorial disease comprising a wide spectrum of ocular surface alterations and symptoms of discomfort. In most patients with aqueous-deficient dry eye, pharmaceutical tear substitutes are used to control symptoms and prevent ocular surface damage. However, in severe dry eye conditions caused by cicatricial disorders, such as Stevens-Johnson syndrome and ocular cicatricial mucous membrane pemphigoid, noninvasive treatments are insufficient, and patients are at risk of developing complications that can lead to blindness. The use of salivary glands as a source of lubrication to treat severe cases of dry eye has been proposed by different authors. The first reports proposed parotid or submandibular gland duct transplantation into the conjunctival fornix. However, complications limited the functional outcomes. Minor salivary gland autotransplantation together with labial mucosa has been used as a complex graft to the conjunctival fornix in severe dry eye with a good outcome. Our group demonstrated significant improvements in best-corrected visual acuity, Schirmer I test score, corneal transparency, and neovascularization after using this technique. A symptoms questionnaire applied to these patients revealed improvements in foreign body sensation, photophobia, and pain. Similar to tears, saliva has a complex final composition comprising electrolytes, immunoglobulins, proteins, enzymes, and mucins. We demonstrated the viability of minor salivary glands transplanted into the fornix of patients with dry eye by performing immunohistochemistry on graft biopsies with antibodies against lactoferrin, lysozyme, MUC1, and MUC16. The findings revealed the presence of functional salivary gland units, indicating local production of proteins, enzymes, and mucins.

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

Recent Perspectives in Ocular Drug Delivery

PubMed Central

Gaudana, Ripal; Jwala, J.; Boddu, Sai H. S.; Mitra, Ashim K.

2015-01-01

Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders. PMID:18758924

Lenalidomide, an anti-tumor drug, regulates retinal endothelial cell function: Implication for treating ocular neovascular disorder

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

Dong, Ling-Feng; Yao, Jin; Wang, Xiao-Qun

Ocular angiogenesis is an important pathologic character of several ocular diseases, such as retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration (AMD). Inhibition of ocular angiogenesis has great therapeutic value for treating these dieses. Here we show that lenalidomide, an anti-tumor drug, has great anti-angiogenic potential in ocular diseases. Lenalidomide inhibits retinal endothelial cell viability in normal and pathological condition, and inhibits VEGF-induced endothelial cell migration and tube formation in vitro. Moreover, lenalidomide inhibits ocular angiogenesis in vivo through the reduction of angiogenesis- and inflammation-related protein expression. Collectively, lenalidomide is a promising drug for treating ocular angiogenesis through its anti-proliferative andmore » anti-inflammatory property. - Highlights: • Lenalidomide inhibits retinal endothelial cell viability in vitro. • Lenalidomide inhibits retinal endothelial cell migration and tube formation. • Lenalidomide inhibits pathological ocular angiogenesis in vivo. • Lenalidomide inhibits angiogenesis- and inflammation-related protein expression.« less

Defensins and Other Antimicrobial Peptides at the Ocular Surface

PubMed Central

McDermott, Alison M.

2006-01-01

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

Polyclonality of Staphylococcus epidermidis residing on the healthy ocular surface.

PubMed

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

2007-01-01

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

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

PubMed

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

2012-01-01

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

An historical ophthalmic study of Jane Austen.

PubMed

Wilson, Graham A

2012-11-01

Today, no other classic novelist has the popularity or power of Jane Austen, and in 2013 the world will celebrate 200 years of her comic masterpiece Pride and Prejudice. Her millions of fans have an abiding fascination with all aspects of her life, including her health and the cause of her death. This historical ophthalmic study of Jane Austen, based on very incomplete medical bibliographic data, finds that she had a mild ocular surface disorder from age 23. This disorder did not significantly impact on her visual performance for writing. There are many references to eyes in her novels, but Jane's eyes and those of her characters cannot contribute further to the debate around the cause of her death at age 41.

Eye disorders in newborn infants (excluding retinopathy of prematurity).

PubMed

Wan, Michael J; VanderVeen, Deborah K

2015-05-01

A screening eye examination is an essential part of the newborn assessment. The detection of many ocular disorders in newborn infants can be achieved through careful observation of the infant's visual behaviour and the use of a direct ophthalmoscope to assess the ocular structures and check the red reflex. Early diagnosis and subspecialty referral can have a critical impact on the prognosis for many ocular conditions, including potentially blinding but treatable conditions such as congenital cataracts, life-threatening malignancies such as retinoblastoma and harbingers of disease elsewhere such as sporadic aniridia and its association with the development of Wilms tumour. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The 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.

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

PubMed

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

2012-01-01

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

Ocular health assessment of cocoa farmers in a rural community in Ghana.

PubMed

Boadi-Kusi, Samuel Bert; Hansraj, Rekha; Kumi-Kyereme, Akwasi; Mashige, Khathutshelo Percy; Awusabo-Asare, Kofi; Ocansey, Stephen; Kyei, Samuel

2014-01-01

Cocoa farming provides employment for over 800,000 households in rural Ghana, with the country currently touted as the second largest producer of cocoa worldwide. Agriculture is one of the riskiest occupations for the eyes due to the numerous ocular hazards on farms. The authors conducted an ocular health assessment among cocoa farmers at Mfuom, a rural community in the Central Region of Ghana, to examine the ocular health status and the ocular safety measures used by cocoa farmers. A structured questionnaire was used to evaluate demographic characteristics, ocular injuries, and utilization of eye care services and ocular protection, and a clinical examination was used to evaluate their ocular status. Cocoa farmers were at high risk for ocular injuries and farm-related vision disorders and utilized eye care services and ocular protection poorly. Ocular condition identified were mainly refractive error (28.6%), cataract (20.0%), glaucoma (11.7%), conjunctivitis (13%), pterygium (2.7%), and cornea opacity (2.2%). There is a need for the introduction of an interventional eye care program to help address the ocular health challenges identified among the farmers. This can be done through collaborative efforts by educational institutions, government, and other role players in the agricultural industry to improve the quality of life of the vulnerable cocoa farmers in rural Ghana.

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.

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

PubMed

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

2013-05-01

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

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

PubMed Central

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

2013-01-01

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

Retinal tear presenting in a patient with ectrodactyly ectodermal dysplasia.

PubMed

Grogg, Jane Ann; Port, Nicholas; Graham, Trevor

2014-04-01

This article aims to report a case of known ectrodactyly ectodermal dysplasia in a young male patient who subsequently was found to have a retinal tear and localized retinal detachment. This is a case report of a 22-year-old white male patient with a history of ectrodactyly ectodermal dysplasia. Our patient initially presented with an acute exacerbation of bilateral, red, irritated eyes. No recent changes in vision were reported. The patient's ocular surface disease was consistent with ectrodermal dysplasia syndrome. However, a dilated fundus examination revealed an asymptomatic retinal tear with a surrounding localized retinal detachment. In this case, the patient presented with longstanding ocular surface disease known to be associated with this patient's inherited ectoderm disorder. In addition, this patient revealed a retinal tear, raising the possibility that patients with inherited congenital ectodermal dysplasia could be at risk for damaged structures originating from the neural ectoderm. In this heterogeneous disease, we are contributing to the existing literature a case of ectodermal dysplasia syndrome with obvious ectodermal complications that also had retinal findings leading us to speculate question if neural ectoderm could also be involved in this inherited disease.

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.

Progress in neuro-otology research in the last year.

PubMed

Tarnutzer, Alexander A; Straumann, Dominik

2012-11-01

Herein, we summarize articles in the field of neuro-otology published in the Journal of Neurology over the last year. Topics included acute and chronic vertigo as well as auditory and ocular motor disorders. Characteristic lesion locations in Pusher syndrome are reported and the usefulness of bedside ocular motor tests in vertebrobasilar stroke is revisited. Probing the vestibular system and its value in predicting the outcome in vegetative state is discussed. Several articles address new diagnostic and therapeutic approaches in different disorders associated with chronic vestibular, auditory or gait deficits. In a series of case reports, we focus on different eye movement disorders in the vertical plane, which are often difficult to assess.

Marshall M. Parks Memorial Lecture: Ocular Motor Misbehavior in Children: Where Neuro-Ophthalmology Meets Strabismus.

PubMed

Brodsky, Michael C

2017-06-01

Clinical diagnosis has been supplemented by neuroimaging advances, genetic discoveries, and molecular research to generate new neurobiological discoveries pertaining to early maldevelopment of ocular motor control systems. In this focused review, I examine recent paradigm shifts that have transformed our understanding of pediatric ocular motor disease at the prenuclear and infranuclear levels. The pathogenesis of complex ocular motor disorders, such as paradoxical pupillary constriction to darkness, benign tonic upgaze of infancy, congenital fibrosis syndrome, and the constellation of unique eye movements that accompany Joubert syndrome, are elucidated. Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

A Review of Ocular Graft-Versus-Host Disease.

PubMed

Munir, Saleha Z; Aylward, James

2017-05-01

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

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

PubMed

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

1986-06-01

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

Ocular Motor Indicators of Executive Dysfunction in Fragile X and Turner Syndromes

ERIC Educational Resources Information Center

Lasker, Adrian G.; Mazzocco, Michele M. M.; Zee, David S.

2007-01-01

Fragile X and Turner syndromes are two X-chromosome-related disorders associated with executive function and visual spatial deficits. In the present study, we used ocular motor paradigms to examine evidence that disruption to different neurological pathways underlies these deficits. We tested 17 females with fragile X, 19 females with Turner…

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.

Surveillance of vision and ocular disorders in children with Down syndrome.

PubMed

Stephen, Elma; Dickson, Jennifer; Kindley, A David; Scott, Christopher C; Charleton, Patricia M

2007-07-01

Children with Down syndrome have a high prevalence of ocular disorders. The UK Down's Syndrome Medical Interest Group (DSMIG) guidelines for ophthalmic screening were locally implemented into a protocol that included neonatal eye examination by an ophthalmologist and a comprehensive ophthalmological examination (cycloplegic refraction, ophthalmoscopy, and orthoptic assessment) by at least the age of 3 years, followed by preschool follow-up as indicated. We audited retrospectively surveillance for ocular disorders before and after the DSMIG-based guidelines were locally adopted in 1995. Results were compared for children born before and after the implementation of screening guidelines. A total of 81 children (43 females, 38 males) with Down syndrome were identified. After the DSMIG protocol, 34/36 children received a full ophthalmological examination in the neonatal period, compared with 9/27 children before 1995 (p<0.001). Neonatal screening resulted in the detection of cataracts in three infants. Mean age of first comprehensive ophthalmic screening outside the neonatal period was similar in the two groups (1y 6mo before guidelines vs 1y 9mo after), as were the proportion of children receiving preschool eye checks (27/30 before; 17/18 after). Overall, 65.7% children were screened in accordance with the guidelines, improving to 100% in recent years. At school age, 43% of the study population had significant refractive errors, with 27% having hypermetropia and astigmatism. Earlier prescription of glasses for refractive errors was seen (mean age 5y 6mo before guidelines; 3y 6mo after; p<0.001). Prevalence of other ocular disorders included strabismus (34/72, 47%), nasolacrimal duct obstruction (26/73, 35.6%), cataracts (5/64, 7.8%), and nystagmus (12/72, 16%). Establishment of the DSMIG-based local protocol has streamlined ocular surveillance. It is anticipated that this will improve developmental and functional outcomes in Down syndrome.

The correct diagnosis and therapeutic management of tear dysfunction: recommendations of the P.I.C.A.S.S.O. board.

PubMed

Rolando, Maurizio; Cantera, Emilia; Mencucci, Rita; Rubino, Pierangela; Aragona, Pasquale

2018-04-01

To describe a standard approach to manage tear dysfunction (TD), in order to obtain a clinically favourable outcome. TD is a highly prevalent, yet largely underdiagnosed, condition that affects from 5 to 30% of the population above 50 years old. Left untreated, TD is associated with eye discomfort and ocular surface disease, substantially affecting quality of life. Although the prevalence of this problem is increasing significantly, a standard approach to its prevention and treatment is not available yet. In September 2015, a team of Ocular Surface Italian Experts convened for a roundtable to discuss on the latest knowledge about diagnosis and treatments for TD and the real issues in the management of these patients. The discussion centred on the appropriate definition of TD, proposing a new classification of risk factors and how to identify them, how to make a correct diagnosis choosing the rational therapy (questionnaires, symptoms' time relation, seasonality, low tech diagnostic manoeuvres, specific tests for the detection of tear film disturbances leading to recognition of the level of disease and of the ocular system elements involved), which artificial tear matches the ideal profile for a rational therapy and which questions should be done to the patient. A multi-item flowchart for tear film dysfunction, with point-by-point explanatory guide, to better identify and manage the patient with this disorder is provided. The growing prevalence of TD demands increased attention. An appropriate prevention and a treatment pattern for the patient, combined with greater patient-practitioner interaction, and patient education is offered.

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

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

Cationic Thiolated Poly(aspartamide) Polymer as a Potential Excipient for Artificial Tear Formulations.

PubMed

Budai-Szűcs, Mária; Horvát, Gabriella; Szilágyi, Barnabás Áron; Gyarmati, Benjámin; Szilágyi, András; Berkó, Szilvia; Szabó-Révész, Piroska; Sandri, Giuseppina; Bonferoni, Maria Cristina; Caramella, Carla; Soós, Judit; Facskó, Andrea; Csányi, Erzsébet

2016-01-01

Dry eye disease is a relatively common ocular problem, which causes eye discomfort and visual disorders leading to a decrease in the quality of life. The aim of this study was to find a possible excipient for eye drop formulations, which is able to stabilize the tear film. A cationic thiolated polyaspartamide polymer, poly[(N-mercaptoethylaspartamide)-co-(N-(N',N'-dimethylaminoethyl)aspartamide)] (ThioPASP-DME), was used as a potential vehicle. Besides satisfying the basic requirements, the chemical structure of ThioPASP-DME is similar to those of ocular mucins as it is a protein-like polymer bearing a considerable number of thiol groups. The solution of the polymer is therefore able to mimic the physiological properties of the mucins and it can interact with the mucus layer via disulphide bond formation. The resultant mucoadhesion provides a prolonged residence time and ensures protective effect for the corneal/conjunctival epithelium. ThioPASP-DME also has an antioxidant effect due to the presence of the thiol groups. The applicability of ThioPASP-DME as a potential excipient in eye drops was determined by means of ocular compatibility tests and through examinations of the interactions with the mucosal surface. The results indicate that ThioPASP-DME can serve as a potential eye drop excipient for the therapy of dry eye disease.

[Case report of osteo-odonto keratoprosthesis (Strampelli) and of Dacron keratoprosthesis (Pintucci)].

PubMed

Chammartin, M; Goldblum, D; Früh, B; Wilkens, L; Bosshardt, D; Sarra, G-M

2009-03-01

In severe forms of ocular surface disorders keratoprostheses provide the ultimate possibility to restore vision. They are made of an optical cylinder integrated with a supporting biocompatible or biological haptic. We report on two patients with different types of keratoprostheses. An 88-year-old woman with ocular pemphigoid received in 1970 a bilateral osteo-odonto-keratoprosthesis (Strampelli). A 59-year-old man with refractory corneal ulcer after corneal grafting received in 2003 a keratoprosthesis with supporting Dacron tissue (Pintucci). The course 35 years after implantation of the osteo-odonto-keratoprosthesis was uneventful. Histologically there were no signs of loosening, rejection or infection. The autologous dentin, which was used for the fixation, was still present. The eye with the Dacron fixated prosthesis (Pintucci) had to be enucleated due to a loosening with endophthalmitis one and a half year after implantation. Keratoprostheses with autologous fixation often show good long-term results. On the other hand, prostheses with synthetic material are more often complicated by dislocation and inflammation.

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}\

Hypercholesterolemia-induced ocular disorder: Ameliorating role of phytotherapy.

PubMed

El-Sayyad, Hassan I H; Elmansi, Ahmed A; Bakr, Eman H M

2015-01-01

The ocular region is a complex structure that allows conscious light perception and vision. It is of ecto-mesodermal origin. Cholesterol and polyunsaturated fatty acids are involved in retinal cell function; however, hypercholesterolemia and diabetes impair its function. Retinal damage, neovascularization, and cataracts are the main complications of cholesterol overload. Dietary supplementation of selected plant products can lead to the scavenging of free reactive oxygen species, thereby protecting the ocular regions from the damage of hypercholesterolemia. This review illustrates the dramatic effects of increased cholesterol levels on the ocular regions. The effect of phytotherapy is discussed in relation to the different regions of the eye, including the retina, cornea, and lens. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Ophthalmologic abnormalities among students with cognitive impairment in eastern Taiwan: The special group with undetected visual impairment.

PubMed

Tsao, Wei-Shan; Hsieh, Hsi-Pao; Chuang, Yi-Ting; Sheu, Min-Muh

2017-05-01

Students with cognitive impairment are at increased risk of suffering from visual impairment due to refractive errors and ocular disease, which can adversely influence learning and daily activities. The purpose of this study was to evaluate the ocular and visual status among students at the special education school in Hualien. All students at the National Hualien Special Education School were evaluated. Full eye examinations were conducted by a skilled ophthalmologist. The students' medical records and disability types were reviewed. A total of 241 students, aged 7-18 years, were examined. Visual acuity could be assessed in 138 students. A total of 169/477 (35.4%) eyes were found to suffer from refractive errors, including 20 eyes with high myopia (≤-6.0 D) and 16 eyes with moderate hypermetropia (+3.0 D to +5.0 D). A total of 84/241 (34.8%) students needed spectacles to correct their vision, thus improving their daily activities and learning process, but only 15/241 (6.2%) students were wearing suitable corrective spectacles. A total of 55/241 students (22.8%) had ocular disorders, which influenced their visual function. The multiple disability group had a statistically significant higher prevalence of ocular disorders (32.9%) than the simple intellectual disability group (19.6%). Students with cognitive impairment in eastern Taiwan have a high risk of visual impairment due to refractive errors and ocular disorders. Importantly, many students have unrecognized correctable refractive errors. Regular ophthalmic examination should be administered to address this issue and prevent further disability in this already handicapped group. Copyright © 2016. Published by Elsevier B.V.

Initial Ophthalmic Findings in Turkish Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Kabatas, Emrah Utku; Ozer, Pinar Altiaylik; Ertugrul, Gokce Tasdemir; Kurtul, Bengi Ece; Bodur, Sahin; Alan, Burcu Ersoz

2015-01-01

Children with autism spectrum disorders (ASD) frequently have ophthalmologic disorders. Due to poor cooperation with ophthalmological examination, ocular abnormalities in such children may be overlooked. We retrospectively studied the records of 324 patients diagnosed as ASD that underwent ophthalmological examination between January 2011 and…

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.

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.

Dry Eye Disease in Patients with Newly Diagnosed Depressive Disorder.

PubMed

Tiskaoglu, Nesime Setge; Yazıcı, Alper; Karlıdere, Tunay; Sari, Esin; Oguz, Elif Yilmaz; Musaoglu, Musa; Aslan, Seyda; Samet Ermiş, Sıtkı

2017-05-01

Psychiatric conditions and not just the treatments themselves might be involved in the pathophysiology of dry eye disease (DED). The aim of our study was to evaluate the association between depression and DED using objective and subjective tests in patients with newly diagnosed depressive disorder who were not using any medication which may help us to determine the sole effect of depression on dry eye. Thirty-six patients from the psychiatry clinic with a new diagnosis of depressive disorder and 32 controls were included in the study. All met the Diagnostic and Statistical Manual IV criteria for depression. Beck Depression Inventory (BDI) was used to measure depression severity and the State-Trait Anxiety Inventory (Stai1, Stai2) for concomitant anxiety symptoms. The Ocular Surface Disease Index (OSDI) and Visual Functioning Questionnaires (VFQ25) were completed and used to confirm diagnosis of DED in conjunction with the tear break up time (TBUT), ocular surface vital dye staining, and Schirmer's test. The comparison of depressive and control groups revealed significantly lower Schirmer (20.3 ± 9.9 vs. 25.7 ± 9.3 mm) and TBUT (7.8 ± 5.7 vs. 12.5 ± 7.8 s) scores with a consistently higher Oxford score (1.8 ± 3.2 vs. 0.2 ± 0.4) in the depressive group. Although the parameters were affected in the depressive group, this did not influence OSDI (86.1 ± 13.6 vs. 86.6 ± 13.3) and VFQ25 (30.8 ± 21.6 vs. 38.5 ± 29.1) scores. In both groups, the three psychological test scores (Stai1-2 and BDI) were correlated to each other but none of these tests were correlated to OSDI, VRQL, Schirmer, TBUT, and Oxford staining scores. Our study shows a definite association between depression and DED. We feel that it is important that psychiatrists take this into account especially while prescribing antidepressants which may aggravate dry eye signs.

Republished review: Gene therapy for ocular diseases.

PubMed

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-07-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Gene therapy for ocular diseases.

PubMed

Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

2011-05-01

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

Case Report: Ocular Myasthenia Gravis Associated with In Vitro Fertilization Procedures.

PubMed

Yoo, Yung Ju; Han, Sang Beom; Yang, Hee Kyung; Hwang, Jeong-Min

2018-05-01

Ocular myasthenia gravis is a localized form of myasthenia gravis, which is a postsynaptic disorder of the neuromuscular junction that causes fluctuating weakness of extraocular muscles resulting from autoimmune mechanisms. In women with myasthenia, changes in sex hormone levels and administration of corticosteroids can trigger or worsen symptoms of myasthenia gravis. To describe a case of seronegative ocular myasthenia gravis whose first symptom appeared a day after in vitro fertilization procedure. A 37-year-old woman suddenly developed mild ptosis and fluctuating diplopia that worsened in the evening. Before the development of symptoms, she had undergone in vitro fertilization procedure and had taken oral steroids. Ocular motility examination revealed an intermittent exotropia in primary gaze at both distance and near. The neostigmine test confirmed her diagnosis as ocular myasthenia gravis. When taking a history for young women with sudden onset of binocular diplopia, steroids and sex hormones should be taken into account, which may trigger or exacerbate symptoms of ocular myasthenia gravis.

Common visual problems in children with disability

PubMed Central

Salt, Alison; Sargent, Jenefer

2014-01-01

Children with disability are at a substantially higher risk of visual impairment (VI) (10.5% compared with 0.16%) but also of ocular disorders of all types, including refractive errors and strabismus. The aetiology of VI in children with disability reflects that of the general population and includes cerebral VI, optic atrophy, as well as primary visual disorders such as retinal dystrophies and structural eye anomalies. VI and other potentially correctable ocular disorders may not be recognised without careful assessment and are frequently unidentified in children with complex needs. Although assessment may be more challenging than in other children, identifying these potential additional barriers to learning and development may be critical. There is a need to develop clearer guidelines, referral pathways and closer working between all professionals involved in the care of children with disability and visual disorders to improve our focus on the assessment of vision and outcomes for children with disability. PMID:25165073

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.

Distribution of CD163-positive cell and MHC class II-positive cell in the normal equine uveal tract.

PubMed

Sano, Yuto; Matsuda, Kazuya; Okamoto, Minoru; Takehana, Kazushige; Hirayama, Kazuko; Taniyama, Hiroyuki

2016-02-01

Antigen-presenting cells (APCs) in the uveal tract participate in ocular immunity including immune homeostasis and the pathogenesis of uveitis. In horses, although uveitis is the most common ocular disorder, little is known about ocular immunity, such as the distribution of APCs. In this study, we investigated the distribution of CD163-positive and MHC II-positive cells in the normal equine uveal tract using an immunofluorescence technique. Eleven eyes from 10 Thoroughbred horses aged 1 to 24 years old were used. Indirect immunofluorescence was performed using the primary antibodies CD163, MHC class II (MHC II) and CD20. To demonstrate the site of their greatest distribution, positive cells were manually counted in 3 different parts of the uveal tract (ciliary body, iris and choroid), and their average number was assessed by statistical analysis. The distribution of pleomorphic CD163- and MHC II-expressed cells was detected throughout the equine uveal tract, but no CD20-expressed cells were detected. The statistical analysis demonstrated the distribution of CD163- and MHC II-positive cells focusing on the ciliary body. These results demonstrated that the ciliary body is the largest site of their distribution in the normal equine uveal tract, and the ciliary body is considered to play important roles in uveal and/or ocular immune homeostasis. The data provided in this study will help further understanding of equine ocular immunity in the normal state and might be beneficial for understanding of mechanisms of ocular disorders, such as equine uveitis.

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

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

Relationship of ocular accommodation and motor skills performance in developmental coordination disorder.

PubMed

Rafique, Sara A; Northway, Nadia

2015-08-01

Ocular accommodation provides a well-focussed image, feedback for accurate eye movement control, and cues for depth perception. To accurately perform visually guided motor tasks, integration of ocular motor systems is essential. Children with motor coordination impairment are established to be at higher risk of accommodation anomalies. The aim of the present study was to examine the relationship between ocular accommodation and motor tasks, which are often overlooked, in order to better understand the problems experienced by children with motor coordination impairment. Visual function, gross and fine motor skills were assessed in children with developmental coordination disorder (DCD) and typically developing control children. Children with DCD had significantly poorer accommodation facility and amplitude dynamics compared to controls. Results indicate a relationship between impaired accommodation and motor skills. Specifically, accommodation anomalies correlated with visual motor, upper limb and fine dexterity task performance. Consequently, we argue accommodation anomalies influence the ineffective coordination of action and perception in DCD. Furthermore, reading disabilities were related to poorer motor performance. We postulate the role of the fastigial nucleus as a common pathway for accommodation and motor deficits. Implications of the findings and recommended visual screening protocols are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Serum Vitamin A Levels May Affect the Severity of Ocular Graft-versus-Host Disease.

PubMed

Tong, Jiefeng; Hu, Renjian; Zhao, Yingying; Xu, Yang; Zhao, Xiaoying; Jin, Xiuming

2017-01-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic option for a range of inherited and acquired hematological disorders. However, graft-versus-host disease (GVHD) remains the leading cause of non-relapse mortality in allogeneic HSCT recipients. Ocular involvement occurs in up to 80% of chronic GVHD patients. In our cases, the diagnosis of vitamin A deficiency was suspected for GVHD patients. Serum vitamin A measurements were conducted to confirm clinical suspicions. Our study revealed significant decrease in serum levels of vitamin A in chronic liver GVHD patients. Although there have been many studies evaluating ocular manifestations in patients with GVHD, the present study is, to our knowledge, the first to study the relationship between vitamin A and ocular manifestations of GVHD in humans. Our data suggest that vitamin A deficiency affects the severity of ocular GVHD in adults.

Prevalence of Presenting Conditions in Grey Seal Pups (Halichoerus grypus) Admitted for Rehabilitation

PubMed Central

Silpa, Marc A. C.; Thornton, Susan M.; Cooper, Tamara; Hedley, Joanna

2015-01-01

A retrospective survey was performed on the presenting conditions of 205 live grey seal pups (Halichoerus grypus) admitted to the Cornish Seal Sanctuary in Gweek, United Kingdom between May 2005 and March 2011. The purpose of the survey was to examine the prevalence of various presenting signs at the sanctuary. The presenting signs were classified into nine non-mutually exclusive categories: ocular disorders, nasal disorders, oral disorders, respiratory disorders, orthopaedic disorders, puncture wounds, abrasions, netting injuries, and onychia. The sex ratio of seal pups in this study was 1.35 males per female. Of the 205 examined for rehabilitation, 22 (10.73%) did not survive to release. 68.78% of grey seal pups presented with puncture wounds, 47.80% with respiratory disorders, 46.34% with ocular disorders, 42.63% malnourished, 36.59% with abrasions, 25.37% with oral disorders, 23.90% with nasal disorders, 11.71% with orthopaedic disorders, 9.27% with onychia, and 3.41% presented with netting injuries. 52% were normothermic, 42% were hyperthermic, and 5% were hypothermic. Associations between gender, outcome of rehabilitation, hospitalisation time and presenting disorders were examined. In addition, admissions rates were found to display seasonality. The results of this study will aid in future preparation of grey seal rehabilitation facilities. PMID:29061924

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.

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

Characterization of patients with ocular myasthenia gravis - A case series.

PubMed

Karni, Arnon; Asmail, Ali; Drory, Vivian E; Kolb, Hadar; Kesler, Anat

2016-09-01

Ocular myasthenia gravis (OMG) is sometimes difficult to diagnose and is probably both under-diagnosed and misdiagnosed. We studied the epidemiological parameters, relevant serology, electromyographic (EMG) findings, and the relationship between OMG and thymoma, thymus hyperplasia and other autoimmune disorders compared to generalized MG (GMG) in a case control study of 133 patients with MG (32 patients with OMG and 101 patients with GMG). The proportion of OMG among all MG patients was relatively high (24.1%). It affected more males than females and its onset was at an older age. Although anti-AChR Ab was detected in fewer OMG patients compared to GMG patients, the rate of positive serology in OMG patients was higher than previously reported. Male OMG patients had a higher positive serology rate than female OMG patients. OMG patients tended to have less supportive EMG evidence of neuromuscular disorder. Female OMG patients had higher rates of thymus hyperplasia and higher rates of other autoimmune disorders than males. Diagnosing MG in patients with solitary ocular manifestation may be difficult due to lower rates of paraclinic supportive tests. Awareness of the characteristics of OMG is important in order to avoid delayed or misdiagnosis of MG and to prevent avoidable iatrogenic complications.

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.

Abnormal Vestibulo-Ocular Reflexes in Autism: A Potential Endophenotype

DTIC Science & Technology

2013-06-01

Annual Report for 15 May 2012 – 14 May 2013 8 Table 5. Summary of Gaze Evoked Nystagmus Tests (no differences between groups) Target...abnormalities of vestibulo-ocular reflexes (VOR) in Autism Spectrum Disorder (ASD). Specific Aim 1: Characterize horizontal VOR post-rotary nystagmus ...without optokinetic feedback using a velocity step test. We hypothesize that in ASD vertical eye movement intrusions during horizontal nystagmus will

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.

Cationic Thiolated Poly(aspartamide) Polymer as a Potential Excipient for Artificial Tear Formulations

PubMed Central

Budai-Szűcs, Mária; Horvát, Gabriella; Szilágyi, Barnabás Áron; Gyarmati, Benjámin; Szilágyi, András; Berkó, Szilvia; Szabó-Révész, Piroska; Sandri, Giuseppina; Bonferoni, Maria Cristina; Caramella, Carla; Soós, Judit; Facskó, Andrea; Csányi, Erzsébet

2016-01-01

Dry eye disease is a relatively common ocular problem, which causes eye discomfort and visual disorders leading to a decrease in the quality of life. The aim of this study was to find a possible excipient for eye drop formulations, which is able to stabilize the tear film. A cationic thiolated polyaspartamide polymer, poly[(N-mercaptoethylaspartamide)-co-(N-(N′,N′-dimethylaminoethyl)aspartamide)] (ThioPASP-DME), was used as a potential vehicle. Besides satisfying the basic requirements, the chemical structure of ThioPASP-DME is similar to those of ocular mucins as it is a protein-like polymer bearing a considerable number of thiol groups. The solution of the polymer is therefore able to mimic the physiological properties of the mucins and it can interact with the mucus layer via disulphide bond formation. The resultant mucoadhesion provides a prolonged residence time and ensures protective effect for the corneal/conjunctival epithelium. ThioPASP-DME also has an antioxidant effect due to the presence of the thiol groups. The applicability of ThioPASP-DME as a potential excipient in eye drops was determined by means of ocular compatibility tests and through examinations of the interactions with the mucosal surface. The results indicate that ThioPASP-DME can serve as a potential eye drop excipient for the therapy of dry eye disease. PMID:27313866

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

Linkage mapping of the primary disease locus for collie eye anomaly.

PubMed

Lowe, Jennifer K; Kukekova, Anna V; Kirkness, Ewen F; Langlois, Mariela C; Aguirre, Gustavo D; Acland, Gregory M; Ostrander, Elaine A

2003-07-01

Collie eye anomaly (cea) is a hereditary ocular disorder affecting development of the choroid and sclera segregating in several breeds of dog, including rough, smooth, and Border collies and Australian shepherds. The disease is reminiscent of the choroidal hypoplasia phenotype observed in humans in conjunction with craniofacial or renal abnormalities. In dogs, however, the clinical phenotype can vary significantly; many dogs exhibit no obvious clinical consequences and retain apparently normal vision throughout life, while severely affected animals develop secondary retinal detachment, intraocular hemorrhage, and blindness. We report genetic studies establishing that the primary cea phenotype, choroidal hypoplasia, segregates as an autosomal recessive trait with nearly 100% penetrance. We further report linkage mapping of the primary cea locus to a 3.9-cM region of canine chromosome 37 (LOD = 22.17 at theta = 0.076), in a region corresponding to human chromosome 2q35. These results suggest the presence of a developmental regulatory gene important in ocular embryogenesis, with potential implications for other disorders of ocular vascularization.

Nystagmus and oscillopsia.

PubMed

Straube, A; Bronstein, A; Straumann, D

2012-01-01

The ocular motor system consists of several subsystems, including the vestibular ocular nystagmus saccade system, the pursuit system, the fixation and gaze-holding system and the vergence system. All these subsystems aid the stabilization of the images on the retina during eye and head movements and any kind of disturbance of one of the systems can cause instability of the eyes (e.g. nystagmus) or an inadequate eye movement causing a mismatch between head and eye movement (e.g. bilateral vestibular failure). In both situations, the subjects experience a movement of the world (oscillopsia) which is quite disturbing. New insights into the patho-physiology of some of the ocular motor disorders have helped to establish new treatment options, in particular in downbeat nystagmus, upbeat nystagmus, periodic alternating nystagmus, acquired pendular nystagmus and paroxysmal vestibular episodes/attacks. The discussed patho-physiology of these disorders and the current literature on treatment options are discussed and practical treatment recommendations are given in the paper. © 2011 The Author(s). European Journal of Neurology © 2011 EFNS.

Incidence and Long-term Outcomes of the HIV-Neuroretinal Disorder in Patients with the Acquired Immunodeficiency Syndrome

PubMed Central

Jabs, Douglas A.; Drye, Lea; Van Natta, Mark L.; Thorne, Jennifer E.; Holland, Gary N.

2014-01-01

Objectives Patients with the acquired immunodeficiency syndrome (AIDS) have an abnormality of retina/optic nerve function, manifested as decreased contrast sensitivity (in the absence of ocular opportunistic infections or media opacity), abnormalities on automated perimetry, and loss of retinal nerve fiber layer, even among those with good visual acuity, termed the HIV-neuroretinal disorder. The objectives of this study were to determine the prevalence, incidence, risk factors for, and outcomes of HIV-neuroretinal disorder. Design Prospective cohort study Participants 1822 patients with AIDS without ocular infections or media opacities. Methods Patients with HIV-neuroretinal disorder were identified by a contrast sensitivity < 1.50 log units in either eye in the absence of ocular opportunistic infections or media opacity. Main outcome measures Incidence of HIV-neuroretinal disorder, mortality, visual impairment (visual acuity 20/50 or worse), and blindness (20/200 or worse) on logarithmic visual acuity charts. Results Sixteen percent of participants had HIV-neuroretinal disorder at enrollment. The estimated cumulative incidence by 20 years after AIDS diagnosis was 51% (95% confidence interval [CI] 46%–55%). HIV-neuroretinal disorder was more common in women and African American persons. Risk factors for it included hepatitis C infection, low CD4+ T cells, and detectable HIV RNA in the blood. Patients with HIV neuroretinal disorder had a 70% excess mortality vs. those without it, even after adjusting for CD4+ T cells and HIV load (hazard ratio=1.7, 95% CI= 1.3–2.1, P<0.0001). Patients with HIV-neuroretinal disorder had increased risks of bilateral visual impairment (hazard ratio=6.5, 95% CI=2.6–10.6, P<0.0001) and blindness (hazard ratio=5.9, 95% CI=2.8–13.7, P=0.01) vs. those without HIV neuroretinal disorder. Conclusions HIV-neuroretinal disorder is a common finding among patients with AIDS, and it is associated with an increased mortality and an increased risk of visual impairment. Successful antiretroviral therapy decreases but does not eliminate the risk of HIV-neuroretinal disorder. PMID:25600199

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.

Moebius Sequence and Autism Spectrum Disorders--Less Frequently Associated than Formerly Thought

ERIC Educational Resources Information Center

Briegel, Wolfgang; Schimek, Martina; Kamp-Becker, Inge

2010-01-01

Moebius sequence is a rare congenital disorder usually defined as a combination of facial weakness with impairment of ocular abduction. It is questionable, whether there is a strong association of the sequence with autism spectrum disorders (ASDs) as suggested in some earlier case reports and studies. Twenty-two participants with Moebius sequence…

Lacritin and other new proteins of the lacrimal functional unit.

PubMed

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

2009-05-01

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

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

PubMed Central

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

2004-01-01

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

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

PubMed

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

2015-01-01

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

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.

A thermoreversible hydrogel as a biosynthetic bandage for corneal wound repair.

PubMed

Pratoomsoot, Chayanin; Tanioka, Hidetoshi; Hori, Kuniko; Kawasaki, Satoshi; Kinoshita, Shigeru; Tighe, Patrick J; Dua, Harminder; Shakesheff, Kevin M; Rose, Felicity Rosamari A J

2008-01-01

Ocular trauma and disorders that lead to corneal blindness account for over 2 million new cases of monocular blindness every year. A popular ocular surface reconstruction therapy, amniotic membrane transplantation, has been shown to aid corneal wound repair. However, the success rates of the procedure are variable. Here, we proposed to bioengineer a novel synthetic material that would serve as a biomimetic corneal bandage. The PLGA-PEG-PLGA triblock copolymer was synthesised via ring-opening polymerisation. Thermoreversible gelation behaviour was investigated at different polymer concentrations (23%, 30%, 35%, 40%, 45%, w/v) at temperatures ranging between 5 and 60 degrees C. Viscoelastic properties were studied in dynamic mechanical analysis with 1 degrees C/min temperature ramp. Cryo-SEM revealed a porous hydrogel with interconnecting networks. No adverse cytotoxicity was observed with an in vitro scratch-wound assay and in in vivo biocompatibility tests. We have demonstrated that the PLGA-PEG-PLGA hydrogel possessed a suitable gelling profile and, for the first time, the biocompatibility properties for this application as a potential bandage for corneal wound repair.

Lipid nanoparticles as drug/gene delivery systems to the retina.

PubMed

del Pozo-Rodríguez, Ana; Delgado, Diego; Gascón, Alicia R; Solinís, Maria Ángeles

2013-03-01

This review highlights the application of lipid nanoparticles (Solid Lipid Nanoparticles, Nanostructured Lipid Carriers, or Lipid Drug Conjugates) as effective drug/gene delivery systems for retinal diseases. Most drug products for ocular disease treatment are marketed as eye drop formulations but, due to ocular barriers, the drug concentration in the retina hardly ever turns out to be effective. Up to this date, several delivery systems have been designed to deliver drugs to the retina. Drug delivery strategies may be classified into 3 groups: noninvasive techniques, implants, and colloidal carriers. The best known systems for drug delivery to the posterior eye are intravitreal implants; in fact, some of them are being clinically used. However, their long-term accumulation might impact the patient's vision. On the contrary, colloidal drug delivery systems (microparticles, liposomes, or nanoparticles) can be easily administered in a liquid form. Nanoparticular systems diffuse rapidly and are better internalized in ocular tissues than microparticles. In comparison with liposomes, nanoparticles have a higher loading capacity and are more stable in biological fluids and during storage. In addition, their capacity to adhere to the ocular surface and interact with the endothelium makes these drug delivery systems interesting as new therapeutic tools in ophthalmology. Within the group of nanoparticles, those composed of lipids (Solid Lipid Nanoparticles, Nanostructred Lipid Carriers, and Lipid Drug Conjugates) are more biocompatible, easy to produce at large scale, and they may be autoclaved or sterilized. The present review summarizes scientific results that evidence the potential application of lipid nanoparticles as drug delivery systems for the retina and also as nonviral vectors in gene therapy of retina disorders, although much more effort is still needed before these lipidic systems could be available in the market.

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.

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.

Ultra High-Resolution Anterior Segment Optical Coherence Tomography in the Diagnosis and Management of Ocular Surface Squamous Neoplasia

PubMed Central

Thomas, Benjamin J.; Galor, Anat; Nanji, Afshan A.; Sayyad, Fouad El; Wang, Jianhua; Dubovy, Sander R.; Joag, Madhura G.; Karp, Carol L.

2014-01-01

The development of optical coherence tomography (OCT) technology has helped to usher in a new era of in vivo diagnostic imaging of the eye. The utilization of OCT for imaging of the anterior segment and ocular surface has evolved from time-domain devices to spectral-domain devices with greater penetrance and resolution, providing novel images of anterior segment pathology to assist in diagnosis and management of disease. Ocular surface squamous neoplasia (OSSN) is one such pathology that has proven demonstrable by certain anterior segment OCT machines, specifically the newer devices capable of performing ultra high-resolution OCT (UHR-OCT). Distinctive features of OSSN on high resolution OCT allow for diagnosis and differentiation from other ocular surface pathologies. Subtle findings on these images help to characterize the OSSN lesions beyond what is apparent with the clinical examination, providing guidance for clinical management. The purpose of this review is to examine the published literature on the utilization of UHR-OCT for the diagnosis and management of OSSN, as well as to report novel uses of this technology and potential directions for its future development. PMID:24439046

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.

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.

Eye disorders associated with obstructive sleep apnoea.

PubMed

West, Sophie D; Turnbull, Chris

2016-11-01

Obstructive sleep apnoea (OSA) is increasing in prevalence due to rising obesity. Public awareness is also growing. Although OSA is a disorder primarily of the upper airway during sleep, its physiological impact on other parts of the body is now well recognized. There is increasing interest in the association of OSA with various eye disorders. Work in this field has been directed predominantly to OSA prevalence and association studies, but some authors have tried to elucidate the effect of OSA therapies on eye diseases, including continuous positive airway pressure, upper airway surgery or bariatric surgery. This review discusses the publications in this area from the past year. The key ocular disorders featured in the studies and meta-analayses include glaucoma, floppy eyelid syndrome, nonarteritic ischaemic optic neuropathy, keratoconus, age-related macular degeneration and diabetic retinopathy. Associations with OSA were found with all these conditions, but aspects of the studies still leave gaps in our knowledge. This review highlights the need for ophthalmologists to consider OSA in their patients and also makes recommendations for future research studies, especially whether therapies for OSA can be effective for ocular disorders also.

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

PubMed

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

2004-09-01

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

Recent developments on dry eye disease treatment compounds.

PubMed

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

2014-01-01

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

Periocular Reconstruction in Patients with Facial Paralysis.

PubMed

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

2016-04-01

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

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

PubMed

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

2015-06-01

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

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

PubMed

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

2018-07-01

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

Dry eye disease as an inflammatory disorder.

PubMed

Calonge, Margarita; Enríquez-de-Salamanca, Amalia; Diebold, Yolanda; González-García, María J; Reinoso, Roberto; Herreras, José M; Corell, Alfredo

2010-08-01

Dry eye disease (DED) is a prevalent inflammatory disorder of the lacrimal functional unit of multifactorial origin leading to chronic ocular surface disease, impaired quality of vision, and a wide range of complications, eventually causing a reduction in quality of life. It still is a frustrating disease because of the present scarcity of therapies that can reverse, or at least stop, its progression. A comprehensive literature survey of English-written scientific publications on the role of inflammation in DED. New investigations have demonstrated that a chronic inflammatory response plays a key role in the pathogenesis of human DED. Additionally, correlations between inflammatory molecules and clinical data suggest that inflammation can be responsible for some of the clinical symptoms and signs. Research efforts to clarify its pathophysiology are leading to a better understanding of DED, demonstrating that inflammation, in addition to many other factors, plays a relevant role.

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.

Neurological disorders associated with DNA strand-break processing enzymes

PubMed Central

Jiang, Bingcheng; Glover, J.N. Mark

2016-01-01

The termini of DNA strand breaks induced by reactive oxygen species or by abortive DNA metabolic intermediates require processing to enable subsequent gap filling and ligation to proceed. The three proteins, tyrosyl DNA-phosphodiesterase 1 (TDP1), aprataxin (APTX) and polynucleotide kinase/phosphatase (PNKP) each act on a discrete set of modified strand-break termini. Recently, a series of neurodegenerative and neurodevelopmental disorders have been associated with mutations in the genes coding for these proteins. Mutations in TDP1 and APTX have been linked to Spinocerebellar ataxia with axonal neuropathy (SCAN1) and Ataxia-ocular motor apraxia 1 (AOA1), respectively, while mutations in PNKP are considered to be responsible for Microcephaly with seizures (MCSZ) and Ataxia-ocular motor apraxia 4 (AOA4). Here we present an overview of the mechanisms of these proteins and how their impairment may give rise to their respective disorders. PMID:27470939

Changes in tear volume and ocular symptoms of patients receiving oral anticancer drug S-1.

PubMed

Kuriki, Reiko; Hata, Tsuyoshi; Nakayama, Kinuyo; Ito, Yuichi; Misawa, Kazunari; Ito, Seiji; Tatematsu, Michiko; Kaneda, Norio

2018-01-01

Most eye disorders are not fatal but may deteriorate the quality of life of a patient. The eye disorder that is most frequently reported in the cancer chemotherapy is associated with the combination of tegafur/gimeracil/potassium oxonate (S-1). However, preventive methods or treatment methods for the eye disorder have not yet been established. This study aimed to determine changes in tear volume and subjective ocular symptoms during the treatment period in patients receiving S-1 monotherapy for early detection of adverse effects in the eye and establishment of its treatment methods. This study included eleven patients receiving S-1 monotherapy as a postoperative adjuvant chemotherapy for gastric cancer. Six subjective ocular symptoms including watering eyes were evaluated and changes in tear volume measured by the Schirmer's test in patients receiving S-1 during the treatment period. In the present study, the patients were divided into "no watering eyes" (patients not experienced watering eyes) group and "watering eyes" (patients experienced watering eyes even once) group. Six out of eleven patients developed watering eyes after receiving S-1 monotherapy. Among these, the earliest onset occurred on the 2nd week after oral administration. Watering eyes and eye discharge were highly related in patients having a trouble in daily life due to the decreased QOL. Changes in tear volume in the "watering eyes" group significantly increased compared to the "no watering eyes" group during the treatment period, especially when the patients had no subjective symptom of the increased tear volume. It is essential to prevent eye disorders including watering eyes as an adverse effect of S-1 administration. The present study recommends that the tear volume should be periodically measured using Schirmer's test, and the patient should be interviewed regarding the subjective ocular symptoms for the early detection of watering eyes caused by S-1 administration. If the tear volume can not be measured periodically, medical staffs should pay attention to the patient with eye discharge.

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.

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

PubMed

Gulati, Shilpa; Jain, Sandeep

2017-01-01

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

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

Evaluation of the Ocular Tolerance of Three Tacrolimus Topical Pharmaceutical Preparations by Bovine Corneal Opacity and Permeability Test.

PubMed

Pastor-Clerigues, Alfonso; Serrano, Adela; Milara, Javier; Marti-Bonmati, Ezequiel; Lopez-Perez, Francisco J; Garcia-Montanes, Sara; Sanfeliu, Joan; Saval-Victoria, Ana C; Cortijo, Julio

2016-07-01

Tacrolimus ocular preparations are commonly employed in autoimmune or inflammatory ocular disorders. However, currently there are not yet approved ocular formulations. Tacrolimus ocular side effects have been reported in clinical use, so the evaluation of different pharmaceutical preparations is mandatory. In this study, the local corneal tolerance and safety profile of three common tacrolimus 0.03% pharmaceutical preparations were evaluated. Corneal irritation and permeability of tacrolimus preparations were evaluated with the bovine corneal opacity and permeability (BCOP) test. Complementary corneal hematoxylin/eosin and immunohistochemistry staining for tight junctions and adherent junctions E-cadherin, VE-cadherin and zonula occludens-1 were examined and scored to evaluate and to confirm corneal disruption and irritation scores obtained with the BCOP method. Commercial brand ointment (Protopic®), topical compounded eye ointment (pharmacy elaboration) and tacrolimus suspension eye drops (elaborated from parenteral prograf®) were tested as potential ocular preparations to be used in clinics. Tacrolimus preparations hereby studied do not alter the opacity and permeability of the bovine cornea by more than three units, measured by the In Vitro Irritancy Score, neither affected the immunohistochemical parameters, composite score or transepithelial electrical resistance. Tacrolimus preparations studied can be safely applied as a topical ocular treatment.

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.

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

PubMed

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

2017-10-01

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

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

PubMed

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

2004-01-01

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

Recent developments on dry eye disease treatment compounds

PubMed Central

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

2013-01-01

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

Dry eyes: etiology and management.

PubMed

Latkany, Robert

2008-07-01

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

Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies

ClinicalTrials.gov

2018-03-21

Congenital Fibrosis of Extraocular Muscles; Duane Retraction Syndrome; Duane Radial Ray Syndrome; Mobius Syndrome; Brown Syndrome; Marcus Gunn Syndrome; Strabismus Congenital; Horizontal Gaze Palsy; Horizontal Gaze Palsy With Progressive Scoliosis; Facial Palsy; Facial Paresis, Hereditary, Congenital; Third Nerve Palsy; Fourth Nerve Palsy; Sixth Nerve Palsy; Synkinesis; Ocular Motility Disorders; Levator-Medial Rectus Synkinesis; Athabaskan Brainstem Dysgenesis; Tongue Paralysis; Ninth Nerve Disorder; Fifth Nerve Palsy; Seventh Nerve Palsy; Eleventh Nerve Disorder; Twelfth Nerve Disorder; Vagus Nerve Paralysis; Moebius Sequence

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

Aberrant ocular architecture and function in patients with Klinefelter syndrome.

PubMed

Brand, Cristin; Zitzmann, Michael; Eter, Nicole; Kliesch, Sabine; Wistuba, Joachim; Alnawaiseh, Maged; Heiduschka, Peter

2017-10-13

Klinefelter Syndrome (KS), the most common chromosomal disorder in men (47,XXY), is associated with numerous comorbidities. Based on a number of isolated case reports, we performed the first systematic and comprehensive evaluation of eye health in KS patients with a focus on ocular structure and vascularization. Twenty-one KS patients and 26 male and 38 female controls underwent a variety of non-invasive examinations investigating ocular morphology (examination of retinal thickness, optic nerve head, and cornea) and function (visual field testing and quantification of ocular vessel density by optical coherence tomography angiography). In comparison to healthy controls, KS patients exhibited a smaller foveal avascular zone and a decreased retinal thickness due to a drastically thinner outer nuclear layer. The cornea of KS patients showed a decreased peripheral thickness and volume. In perimetry evaluation, KS patients required brighter stimuli and gave more irregular values. KS patients show an ocular phenotype including morphological and functional features, which is very likely caused by the supernumerary X chromosome. Thus, KS should not be limited to infertility, endocrine dysfunction, neurocognitive and psychosocial comorbidities. Defining an aberrant ocular morphology and function, awareness for possible eye problems should be raised.

Detection of myasthenia gravis using electrooculography signals.

PubMed

Liang, T; Boulos, M I; Murray, B J; Krishnan, S; Katzberg, H; Umapathy, K

2016-08-01

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder resulting from skeletal muscle weakness and fatigue. An early common symptom is fatigable weakness of the extrinsic ocular muscles; if symptoms remain confined to the ocular muscles after a few years, this is classified as ocular myasthenia gravis (OMG). Diagnosis of MG when there are mild, isolated ocular symptoms can be difficult, and currently available diagnostic techniques are insensitive, non-specific or technically cumbersome. In addition, there are no accurate biomarkers to follow severity of ocular dysfunction in MG over time. Single-fiber electromyography (SFEMG) and repetitive nerve stimulation (RNS) offers a way of detecting and measuring ocular muscle dysfunction in MG, however, challenges of these methods include a poor signal to noise ratio in quantifying eye muscle weakness especially in mild cases. This paper presents one of the attempts to use the electric potentials from the eyes or electrooculography (EOG) signals but obtained from three different forms of sleep testing to differentiate MG patients from age- and gender-matched controls. We analyzed 8 MG patients and 8 control patients and demonstrated a difference in the average eye movements detected between the groups. A classification accuracy as high as 68.8% was achieved using a linear discriminant analysis based classifier.

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

PubMed Central

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

2017-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2009-11-01

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

Inhibition of Ultraviolet B-Induced Expression of the Proinflammatory Cytokines TNF-α and VEGF in the Cornea by Fucoxanthin Treatment in a Rat Model.

PubMed

Chen, Shiu-Jau; Lee, Ching-Ju; Lin, Tzer-Bin; Liu, Hsiang-Jui; Huang, Shuan-Yu; Chen, Jia-Zeng; Tseng, Kuang-Wen

2016-01-07

Ultraviolet B (UVB) irradiation is the most common cause of radiation damage to the eyeball and is a risk factor for human corneal damage. We determined the protective effect of fucoxanthin, which is a carotenoid found in common edible seaweed, on ocular tissues against oxidative UVB-induced corneal injury. The experimental rats were intravenously injected with fucoxanthin at doses of 0.5, 5 mg/kg body weight/day or with a vehicle before UVB irradiation. Lissamine green for corneal surface staining showed that UVB irradiation caused serious damage on the corneal surface, including severe epithelial exfoliation and deteriorated epithelial smoothness. Histopathological lesion examination revealed that levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF), significantly increased. However, pretreatment with fucoxanthin inhibited UVB radiation-induced corneal disorders including evident preservation of corneal surface smoothness, downregulation of proinflammatory cytokine expression, and decrease of infiltrated polymorphonuclear leukocytes from UVB-induced damage. Moreover, significant preservation of the epithelial integrity and inhibition of stromal swelling were also observed after UVB irradiation in fucoxanthin-treated groups. Pretreatment with fucoxanthin may protect against UVB radiation-induced corneal disorders by inhibiting expression of proinflammatory factors, TNF-α, and VEGF and by blocking polymorphonuclear leukocyte infiltration.

Dextran and protamine-based solid lipid nanoparticles as potential vectors for the treatment of X-linked juvenile retinoschisis.

PubMed

Delgado, Diego; del Pozo-Rodríguez, Ana; Solinís, Maria Ángeles; Avilés-Triqueros, Marcelino; Weber, Bernhard H F; Fernández, Eduardo; Gascón, Alicia R

2012-04-01

The goal of the present study was to analyze the potential application of nonviral vectors based on solid lipid nanoparticles (SLN) for the treatment of ocular diseases by gene therapy, specifically X-linked juvenile retinoschisis (XLRS). Vectors were prepared with SLN, dextran, protamine, and a plasmid (pCMS-EGFP or pCEP4-RS1). Formulations were characterized and the in vitro transfection capacity as well as the cellular uptake and the intracellular trafficking were studied in ARPE-19 cells. Formulations were also tested in vivo in Wistar rat eyes, and the efficacy was studied by monitoring the expression of enhanced green fluorescent protein (EGFP) after intravitreal, subretinal, and topical administration. The presence of dextran and protamine in the SLN improved greatly the expression of retinoschisin and EGFP in ARPE-19 cells. The nuclear localization signals of protamine, its ability to protect the DNA, and a shift in the entry mechanism from caveola-mediated to clathrin-mediated endocytosis promoted by the dextran, justify the increase in transfection. After ocular administration of the dextran-protamine-DNA-SLN complex to rat eyes, we detected the expression of EGFP in various types of cells depending on the administration route. Our vectors were also able to transfect corneal cells after topical application. We have demonstrated the potential usefulness of our nonviral vectors loaded with XLRS1 plasmid and provided evidence for their potential application for the management or treatment of degenerative retinal disorders as well as ocular surface diseases.

Dental stem cells: a future asset of ocular cell therapy.

PubMed

Yam, Gary Hin-Fai; Peh, Gary Swee-Lim; Singhal, Shweta; Goh, Bee-Tin; Mehta, Jodhbir S

2015-11-10

Regenerative medicine using patient's own stem cells (SCs) to repair dysfunctional tissues is an attractive approach to complement surgical and pharmacological treatments for aging and degenerative disorders. Recently, dental SCs have drawn much attention owing to their accessibility, plasticity and applicability for regenerative use not only for dental, but also other body tissues. In ophthalmology, there has been increasing interest to differentiate dental pulp SC and periodontal ligament SC (PDLSC) towards ocular lineage. Both can commit to retinal fate expressing eye field transcription factors and generate rhodopsin-positive photoreceptor-like cells. This proposes a novel therapeutic alternative for retinal degeneration diseases. Moreover, as PDLSC shares similar cranial neural crest origin and proteoglycan secretion with corneal stromal keratoctyes and corneal endothelial cells, this offers the possibility of differentiating PDLSC to these corneal cell types. The advance could lead to a shift in the medical management of corneal opacities and endothelial disorders from highly invasive corneal transplantation using limited donor tissue to cell therapy utilizing autologous cells. This article provides an overview of dental SC research and the perspective of utilizing dental SCs for ocular regenerative medicine.

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.

[Anophthalmia and microphthalmia requires multidisciplinary care. Many of the children also have other medical problems].

PubMed

Jugård, Ylva; Odersjö, Marie; Topa, Alexandra; Lindgren, Gun; Andersson Grönlund, Marita

2015-07-13

Anophthalmia/microphthalmia (A/M) are rare congenital eye malformations. Early intervention with ocular prosthesis can stimulate orbital growth and prevent facial asymmetry. We reviewed medical records from 18 individuals with A/M (0.8-31 years) treated with ocular prosthesis at Sahlgrenska University Hospital between 2000 and 2012. A majority had other ocular findings. Seven had subnormal visual acuity in the fellow eye, one third were in contact with vision support services and half of the group wore glasses. Eleven individuals had extra-ocular findings such as cardiac defect, hearing impairment and neuropsychiatric disorders, possibly indicating syndromic conditions. We suggest that investigation of A/M children should include ultrasound of the eye, optionally visual evoked potential and magnetic resonance imaging of the CNS. The ophthalmologist should initiate treatment with prosthesis, pediatric assessment, hearing tests and genetic counseling, but should also monitor visual development of the fellow eye.

Calorie restriction (CR) and CR mimetics for the prevention and treatment of age-related eye disorders.

PubMed

Kawashima, Motoko; Ozawa, Yoko; Shinmura, Ken; Inaba, Takaaki; Nakamura, Shigeru; Kawakita, Tetsuya; Watanabe, Mitsuhiro; Tsubota, Kazuo

2013-10-01

The morbidity of ocular diseases, including macular degeneration, diabetic retinopathy, and dry eye disease, has been gradually increasing worldwide. Because these diseases develop from age-associated ocular dysfunctions, interventions against the aging process itself may be a promising strategy for their management. Among the several approaches to interrupt aging processes, calorie restriction (CR) has been shown to recover and/or slow age-related functional declines in various organs, including the eye. Here, we review interventions against the aging process as potential therapeutic approaches to age-related ocular diseases. The effects of CR and CR mimetics in animal models of age-related eye diseases are explored. Furthermore, we discuss the possibilities of expanding this research to prospective studies to elucidate the molecular mechanisms by which CR and/or CR mimetics preserve ocular functions. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Ocular manifestations of gravity inversion.

PubMed

Friberg, T R; Weinreb, R N

To determine the ocular manifestations of inverting the human body into a head-down vertical position, we evaluated normal volunteers with applanation tonometry, fundus photography, fluorescein angiography, and ophthalmodynamometry. Compared with data obtained in the sitting position, the intraocular pressure more than doubled on inversion (35.6 +/- 4 v 14.1 +/- 2.8 mm Hg, n = 16), increasing to levels well within the glaucomatous range. Pressures in the central retinal artery underwent similar increases, while the caliber of the retinal arterioles decreased substantially. External ocular findings associated with gravity inversion included orbital congestion, conjunctival hyperemia, petechiae of the eyelids, excessive tearing (epiphora), and subconjunctival hemorrhage. We suggest that patients with retinal vascular abnormalities, macular degeneration, ocular hypertension, glaucoma, and similar disorders refrain from inversion altogether. Whether normal individuals will suffer irreversible damage from inversion is uncertain, but it seems prudent to recommend that prolonged periods of inverted posturing be avoided.

Developments in Ocular Genetics: 2013 Annual Review

PubMed Central

Aboobakar, Inas F.; Allingham, R. Rand

2014-01-01

Purpose To highlight major advancements in ocular genetics from the year 2013. Design Literature review. Methods A literature search was conducted on PubMed to identify articles pertaining to genetic influences on human eye diseases. This review focuses on manuscripts published in print or online in the English language between January 1, 2013 and December 31, 2013. A total of 120 papers from 2013 were included in this review. Results Significant progress has been made in our understanding of the genetic basis of a broad group of ocular disorders, including glaucoma, age-related macular degeneration, cataract, diabetic retinopathy, keratoconus, Fuchs’ endothelial dystrophy, and refractive error. Conclusions The latest next-generation sequencing technologies have become extremely effective tools for identifying gene mutations associated with ocular disease. These technological advancements have also paved the way for utilization of genetic information in clinical practice, including disease diagnosis, prediction of treatment response and molecular interventions guided by gene-based knowledge. PMID:25097799

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

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.

Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery.

PubMed

Mahlumba, Pakama; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

2016-07-30

Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects.

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.

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.

Ocular promoting activity of grape polyphenols-A review.

PubMed

Natarajan, Sithranga Boopathy; Hwang, Jin-Woo; Kim, Yon-Suk; Kim, Eun-Kyung; Park, Pyo-Jam

2017-03-01

The eye is a sensitive organ with complex optical system involves in the perception of light. Although it has several protective mechanisms by itself, various physiological and metabolic disorders are detrimental to the proper functioning of the visual system. Grape juice has long been used worldwide for its potent medicinal values including ocular promotion. Bioactivities of grape products are highly attributed to the presence of health promoting phytochemicals in them. Some phytochemicals present in the grape juice have been involved in the maintenance of intra-ocular pressure, regulation of glucose metabolisms and suppression of pro-inflammatory cytokines in the system. Particularly, the grape derived phytochemicals involve in minimizing various eye defects such as macular degradation, uvea, cataract formation, red eye, diabetic retinopathy and so on. However, only limited number of studies has been conducted so far focusing the ocular promoting activity of grape polyphenols. In this review, we discuss the role of grape polyphenols in ocular promotion relating their anti-oxidant, anti-microbial, anti-aging, anti-hypertensive and anti-inflammatory properties. Copyright © 2016. Published by Elsevier B.V.

The Educational and Psychological Interventions for Children and Adolescents with Marfan Syndrome.

ERIC Educational Resources Information Center

Stebbins, Molly S.; McIntosh, David E.

Marfan's syndrome is an autosomal dominant chromosomal disorder of connective tissue which may cause major abnormalities in the musculoskeletal, ocular (pertaining to the eye), and cardiovascular systems of the body. A description of this disorder is presented in this paper. It affects approximately .03 to .05% of the population; approximately…

Development of an Interactive Anatomical Three-Dimensional Eye Model

ERIC Educational Resources Information Center

Allen, Lauren K.; Bhattacharyya, Siddhartha; Wilson, Timothy D.

2015-01-01

The discrete anatomy of the eye's intricate oculomotor system is conceptually difficult for novice students to grasp. This is problematic given that this group of muscles represents one of the most common sites of clinical intervention in the treatment of ocular motility disorders and other eye disorders. This project was designed to develop a…

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.

Common visual problems in children with disability.

PubMed

Salt, Alison; Sargent, Jenefer

2014-12-01

Children with disability are at a substantially higher risk of visual impairment (VI) (10.5% compared with 0.16%) but also of ocular disorders of all types, including refractive errors and strabismus. The aetiology of VI in children with disability reflects that of the general population and includes cerebral VI, optic atrophy, as well as primary visual disorders such as retinal dystrophies and structural eye anomalies. VI and other potentially correctable ocular disorders may not be recognised without careful assessment and are frequently unidentified in children with complex needs. Although assessment may be more challenging than in other children, identifying these potential additional barriers to learning and development may be critical. There is a need to develop clearer guidelines, referral pathways and closer working between all professionals involved in the care of children with disability and visual disorders to improve our focus on the assessment of vision and outcomes for children with disability. 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 Comparison Study of Conjunctiva Disorders in Technical and Administrative Sawmill Workers in Nigeria

PubMed Central

Njinaka, Itiyafa; Uhumwangho, Odarosa M; Edema, Omolabake T; Dawodu, Oseluese A; Omoti, Afekhide E

2011-01-01

Background: Workers in the sawmilling industry are at risk of various ocular hazards as a direct result of the sawmilling processes. The aim of this study was to determine the pattern of conjunctival disorders between technical and administrative sawmill workers in Benin, Nigeria. Methods: A cross-sectional study was performed on sawmill workers in Benin, Nigeria, between January and May 2009, with the aid of pre-tested questionnaires. Ocular examination was performed on all subjects. Data obtained were recorded and analysed using SPSS version 13. Results: A total of 553 sawmill workers were studied, among whom 449 (81.2%) and 104 (18.8%) were technical and administrative workers, respectively. There were 496 (89.7%) males and 57 (10.3%) females. The age range was 15–80 years, with a mean of 38.9 years (SD 12.8). Pingueculum was found in 127 (23%) workers, among whom 122 (27.2%) were technical workers and 5 (4.8%) were administrative workers. Pterygium was present in 65 (11.8%) workers, among whom 64 (14.3%) were technical workers and 1 (1%) was an administrative worker. Seven (1.6%) technical workers used protective eyewear; 2 (0.4%) wore this protective eyewear regularly. Conclusion: Technical sawmill workers are at risk of developing conjunctival disorders, which result from chronic ocular irritation. This can be prevented by the provision of protective eye devices in the workplace. PMID:22135600

A comparison study of conjunctiva disorders in technical and administrative sawmill workers in Nigeria.

PubMed

Njinaka, Itiyafa; Uhumwangho, Odarosa M; Edema, Omolabake T; Dawodu, Oseluese A; Omoti, Afekhide E

2011-07-01

Workers in the sawmilling industry are at risk of various ocular hazards as a direct result of the sawmilling processes. The aim of this study was to determine the pattern of conjunctival disorders between technical and administrative sawmill workers in Benin, Nigeria. A cross-sectional study was performed on sawmill workers in Benin, Nigeria, between January and May 2009, with the aid of pre-tested questionnaires. Ocular examination was performed on all subjects. Data obtained were recorded and analysed using SPSS version 13. A total of 553 sawmill workers were studied, among whom 449 (81.2%) and 104 (18.8%) were technical and administrative workers, respectively. There were 496 (89.7%) males and 57 (10.3%) females. The age range was 15-80 years, with a mean of 38.9 years (SD 12.8). Pingueculum was found in 127 (23%) workers, among whom 122 (27.2%) were technical workers and 5 (4.8%) were administrative workers. Pterygium was present in 65 (11.8%) workers, among whom 64 (14.3%) were technical workers and 1 (1%) was an administrative worker. Seven (1.6%) technical workers used protective eyewear; 2 (0.4%) wore this protective eyewear regularly. Technical sawmill workers are at risk of developing conjunctival disorders, which result from chronic ocular irritation. This can be prevented by the provision of protective eye devices in the workplace.

Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia-telangiectasia.

PubMed

Shaikh, Aasef G; Marti, Sarah; Tarnutzer, Alexander A; Palla, Antonella; Crawford, Thomas O; Zee, David S; Straumann, Dominik

2013-11-01

Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disorder with prominent eye movement deficits localizing to the cerebellum. We sought to determine if 4-aminopyridine (4-AP), which putatively enhances the precision of Purkinje neurons, could improve the disorders of eye movements and vestibular function in A-T. The influence of 4-AP on disorders of eye movements and vestibular function was studied in four A-T patients. The effects on the cerebellar control of vestibulo-ocular reflex (VOR) was quantitatively assessed by the decay time constant of per- and post-rotational nystagmus during constant velocity en bloc rotations. The length of the VOR time constant determines the fidelity of the vestibular velocity storage, a neural mechanism that increases the bandwidth of VOR under cerebellar control. The VOR time constant was not increased in A-T patients. The latter is explained by the extent of cerebellar lesion as previously described in A-T and other cerebellar disorders. Nevertheless, 4-AP shortened the VOR time constant during horizontal rotations. Severe disinhibition of velocity storage in subjects with putatively profound cerebellar degeneration manifest periodic alternating nystagmus (PAN). Among two A-T subjects who manifested PAN, 4-AP reduced the peak slow phase velocity of the more severely affected individual and abrogated the PAN in the other. Two A-T subjects manifested horizontal and vertical spontaneous nystagmus (SN) in primary gaze, 4-AP reduced its slow phase velocity. We conclude that in subjects with A-T 4-AP has a prominent effect on the ocular motor and vestibular deficits that are ascribed to the loss of cerebellar Purkinje neurons.

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.

Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome

PubMed Central

Bodranghien, Florian; Bastian, Amy; Casali, Carlo; Hallett, Mark; Louis, Elan D.; Mariën, Peter; Nowak, Dennis A.; Schmahmann, Jeremy D.; Serrao, Mariano; Steiner, Katharina Marie; Strupp, Michael; Tilikete, Caroline; Timmann, Dagmar; van Dun, Kim

2017-01-01

The cerebellum is involved in sensorimotor operations, cognitive tasks and affective processes. Here, we revisit the concept of the cerebellar syndrome in the light of recent advances in our understanding of cerebellar operations. The key symptoms and signs of cerebellar dysfunction, often grouped under the generic term of ataxia, are discussed. Vertigo, dizziness, and imbalance are associated with lesions of the vestibulo-cerebellar, vestibulo-spinal, or cerebellar ocular motor systems. The cerebellum plays a major role in the online to long-term control of eye movements (control of calibration, reduction of eye instability, maintenance of ocular alignment). Ocular instability, nystagmus, saccadic intrusions, impaired smooth pursuit, impaired vestibulo-ocular reflex (VOR), and ocular misalignment are at the core of oculomotor cerebellar deficits. As a motor speech disorder, ataxic dysarthria is highly suggestive of cerebellar pathology. Regarding motor control of limbs, hypotonia, a- or dysdiadochokinesia, dysmetria, grasping deficits and various tremor phenomenologies are observed in cerebellar disorders to varying degrees. There is clear evidence that the cerebellum participates in force perception and proprioceptive sense during active movements. Gait is staggering with a wide base, and tandem gait is very often impaired in cerebellar disorders. In terms of cognitive and affective operations, impairments are found in executive functions, visual-spatial processing, linguistic function, and affective regulation (Schmahmann’s syndrome). Nonmotor linguistic deficits including disruption of articulatory and graphomotor planning, language dynamics, verbal fluency, phonological, and semantic word retrieval, expressive and receptive syntax, and various aspects of reading and writing may be impaired after cerebellar damage. The cerebellum is organized into (a) a primary sensorimotor region in the anterior lobe and adjacent part of lobule VI, (b) a second sensorimotor region in lobule VIII, and (c) cognitive and limbic regions located in the posterior lobe (lobule VI, lobule VIIA which includes crus I and crus II, and lobule VIIB). The limbic cerebellum is mainly represented in the posterior vermis. The cortico-ponto-cerebellar and cerebello-thalamocortical loops establish close functional connections between the cerebellum and the supratentorial motor, paralimbic and association cortices, and cerebellar symptoms are associated with a disruption of these loops. PMID:26105056

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

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.

Abnormalities of gaze in cerebrovascular disease.

PubMed

Pedersen, R A; Troost, B T

1981-01-01

Disorders of ocular motility may occur after injury at several levels of the neuraxis. Unilateral supranuclear disorders of gaze tend to be transient; bilateral disorders more enduring. Nuclear disorders of gaze also tend to be enduring and are frequently present in association with long tract signs and cranial nerve palsies on opposite sides of the body. Nystagmus is a reliable sign of posterior fossa or peripheral eight nerve pathology. Familiarity with these concepts may help the clinician answer questions regarding localization and prognosis.

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.

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.

Bioengineered Lacrimal Gland Organ Regeneration in Vivo

PubMed Central

Hirayama, Masatoshi; Tsubota, Kazuo; Tsuji, Takashi

2015-01-01

The lacrimal gland plays an important role in maintaining a homeostatic environment for healthy ocular surfaces via tear secretion. Dry eye disease, which is caused by lacrimal gland dysfunction, is one of the most prevalent eye disorders and causes ocular discomfort, significant visual disturbances, and a reduced quality of life. Current therapies for dry eye disease, including artificial tear eye drops, are transient and palliative. The lacrimal gland, which consists of acini, ducts, and myoepithelial cells, develops from its organ germ via reciprocal epithelial-mesenchymal interactions during embryogenesis. Lacrimal tissue stem cells have been identified for use in regenerative therapeutic approaches aimed at restoring lacrimal gland functions. Fully functional organ replacement, such as for tooth and hair follicles, has also been developed via a novel three-dimensional stem cell manipulation, designated the Organ Germ Method, as a next-generation regenerative medicine. Recently, we successfully developed fully functional bioengineered lacrimal gland replacements after transplanting a bioengineered organ germ using this method. This study represented a significant advance in potential lacrimal gland organ replacement as a novel regenerative therapy for dry eye disease. In this review, we will summarize recent progress in lacrimal regeneration research and the development of bioengineered lacrimal gland organ replacement therapy. PMID:26264034

An Overview on Dry Eye Treatment: Approaches for Cyclosporin A Delivery

PubMed Central

Yavuz, Burçin; Bozdağ Pehlivan, Sibel; Ünlü, Nurşen

2012-01-01

Dry eye syndrome (DES, Keratoconjunctivitis sicca) is a common disorder of the tear film caused by decreased tear production or increased evaporation. Changes in tear composition also promote inflammation on the ocular surface by various mechanisms. Artificial tear drops, tear retention treatment, stimulation of tear secretion, or anti-inflammatory drugs may be used for dry eye treatment according to the severity of the disease. For untreated patients, the risk of ocular infection increases at considerable level and clinical course of the disease may proceed up to infection, corneal ulcer, and blindness. Artificial tears and/or punctual occlusions are used for tear replacement or preservation. New treatment approaches are designed to modify the underlying disease process. For the treatment of severe dry eye disease, cyclosporin A (CsA), the first one of the new generation immunomodulatory drugs, which has an anti-inflammatory effect, is frequently used. CsA has immunosuppressive effects following systemic application. Following local administration of CsA, it is expected to obtain effective drug concentration at the target area and to avoid the various side effects associated with systemic delivery. Microspheres, implants, and liposomes have been developed for administration of CsA subconjunctivally in order to enhance its efficiency. PMID:22619624

An update on dry eye disease molecular treatment: advances in drug pipelines.

PubMed

Colligris, Basilio; Crooke, Almudena; Huete-Toral, Fernando; Pintor, Jesus

2014-07-01

Dry eye disease is a common disorder provoking changes in tear film and ocular surface. Untreated dry eye could cause ocular infections, corneal ulcer and blindness. Only a few drugs are authorized so far for the treatment of dry eye disease and the possibilities of evolution in this sector are immense. Consequently, a significant number of new potential solutions are under development or placed in the pharmaceutical pipeline, promising better results and lesser side effects. In this article, the corresponding literature and recent Phase III clinical trial data and the corresponding literature, for dry eye disease treatment are reviewed, revealing the new strategic movements in drug pipelines. From the clinical trial results, the advancement in tear substitutes and secretagogues in addressing specific deficiencies of tear components even though not resolving the underlying conditions of the disease is evident. The vast majority of new compounds under development are anti-inflammatories, steroids, non-steroids and antibiotics; however, there are also some novel lubricating drops and mucin-tear secretagogues. A future aggressive therapy for dry eye, depending on the severity of the symptoms, would include combinations of soft steroids, anti-inflammatories, such as cyclosporine A, with the addition of the new polyvalent mucin and tear secretagogues.

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.

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.

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.

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.

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.

A review on recent advances in dry eye: Pathogenesis and management

PubMed Central

Bhavsar, Ankita S.; Bhavsar, Samir G.; Jain, Sunita M.

2011-01-01

Keratoconjunctivitis sicca, more commonly known as dry eye, is an extremely common and often unrecognized disease. It is the condition in ophthalmology that in its mild grade of severity will affect most of the population at one time or other. Due to a wide variety of presentations and symptoms, it often frustrates the ophthalmologists as well as patients. Due to multifactorial and elusive etiology, it is often challenging to treat dry eye. Ocular surface disorders are also clinically important to treat especially in terms of visual acuity. Xero-dacryology is therefore becoming a very important branch of ophthalmology. Recent studies have given insight into the inflammatory etiology of dry eye. The conventional and main approach to the treatment of dry eye is providing lubricating eye drops or tear substitutes. However, the newer treatment approach is to target the underlying cause of dry eye instead of conventional symptomatic relief. In light of the above knowledge, the present article focuses on newer theories on pathogenesis of dry eye and their impact on dry eye management. Method of Literature Search: A systematic literature review was performed using PubMed databases in two steps. The first step was oriented to articles published for dry eye. The second step was focused on the role of inflammation and anti-inflammatory therapy for dry eye. The search strategy was not limited by year of publication. A manual literature search was also undertaken from authentic reference books on ocular surface disease. PMID:21897618

Tear dynamics in healthy and dry eyes.

PubMed

Cerretani, Colin F; Radke, C J

2014-06-01

Dry-eye disease, an increasingly prevalent ocular-surface disorder, significantly alters tear physiology. Understanding the basic physics of tear dynamics in healthy and dry eyes benefits both diagnosis and treatment of dry eye. We present a physiological-based model to describe tear dynamics during blinking. Tears are compartmentalized over the ocular surface; the blink cycle is divided into three repeating phases. Conservation laws quantify the tear volume and tear osmolarity of each compartment during each blink phase. Lacrimal-supply and tear-evaporation rates are varied to reveal the dependence of tear dynamics on dry-eye conditions, specifically tear osmolarity, tear volume, tear-turnover rate (TTR), and osmotic water flow. Predicted periodic-steady tear-meniscus osmolarity is 309 and 321 mOsM in normal and dry eyes, respectively. Tear osmolarity, volume, and TTR all match available clinical measurements. Osmotic water flow through the cornea and conjunctiva contribute 10 and 50% to the total tear supply in healthy and dry-eye conditions, respectively. TTR in aqueous-deficient dry eye (ADDE) is only half that in evaporative dry eye (EDE). The compartmental periodic-steady tear-dynamics model accurately predicts tear behavior in normal and dry eyes. Inclusion of osmotic water flow is crucial to match measured tear osmolarity. Tear-dynamics predictions corroborate the use of TTR as a clinical discriminator between ADDE and EDE. The proposed model is readily extended to predict the dynamics of aqueous solutes such as drugs or fluorescent tags.

Infrared ocular thermography in dogs with and without keratoconjunctivitis sicca.

PubMed

Biondi, Flávia; Dornbusch, Peterson T; Sampaio, Manuella; Montiani-Ferreira, Fabiano

2015-01-01

Infrared thermography was used to measure temperature differences of the corneal surface between nasal and temporal limbus regions and central cornea of normal dogs and dogs with keratoconjunctivitis sicca (KCS), in order to establish temperature values in normal canine eyes and in patients with decreased Schirmer tear tests (STT) values. Dogs investigated were all either patients seen at the Veterinary Teaching Hospital of Federal University of Paraná or normal dogs that belonged to the same institution. STT were performed in all eyes. A total of 40 control eyes (STT ≥15 mm/min) and 20 eyes with low STT values (STT ≤14 mm/min) were examined. The mean STT value for eyes with normal STT values was 22.9 ± 3.9 mm/min (mean ± standard deviation), and the mean STT value for eyes with low STT value was 7.2 ± 4.8 mm/min. The mean corneal temperature was significantly lower in eyes with low STT values than in control eyes (P < 0.0001). The following significant correlations were found: (i) Schirmer and breakup time (BUT) (P = 0.0001, r = 0.5); (ii) STT values and corneal surface temperature (P = 0.001, r = 0.256); (iii) STT values and age (P = 0.0001, r = -0.448); (iv) age and corneal surface temperature (P = 0.0001, r = -0.281); and (v) BUT and corneal surface temperature (P = 0.0001, r = 0.36). Thermography is a method that can differentiate between eyes with normal and abnormal STT values. In the future, thermography might be incorporated as part of the ophthalmic examination and perhaps become a popular ancillary test for the diagnoses of ocular surface disorders. © 2013 American College of Veterinary Ophthalmologists.

Whole exome analysis identifies dominant COL4A1 mutations in patients with complex ocular phenotypes involving microphthalmia.

PubMed

Deml, B; Reis, L M; Maheshwari, M; Griffis, C; Bick, D; Semina, E V

2014-11-01

Anophthalmia/microphthalmia (A/M) is a developmental ocular malformation defined as complete absence or reduction in size of the eye. A/M is a heterogenous disorder with numerous causative genes identified; however, about half the cases lack a molecular diagnosis. We undertook whole exome sequencing in an A/M family with two affected siblings, two unaffected siblings, and unaffected parents; the ocular phenotype was isolated with only mild developmental delay/learning difficulties reported and a normal brain magnetic resonance imaging (MRI) in the proband at 16 months. No pathogenic mutations were identified in 71 known A/M genes. Further analysis identified a shared heterozygous mutation in COL4A1, c.2317G>A, p.(Gly773Arg) that was not seen in the unaffected parents and siblings. Analysis of 24 unrelated A/M exomes identified a novel c.2122G>A, p.(Gly708Arg) mutation in an additional patient with unilateral microphthalmia, bilateral microcornea and Peters anomaly; the mutation was absent in the unaffected mother and the unaffected father was not available. Mutations in COL4A1 have been linked to a spectrum of human disorders; the most consistent feature is cerebrovascular disease with variable ocular anomalies, kidney and muscle defects. This study expands the spectrum of COL4A1 phenotypes and indicates screening in patients with A/M regardless of MRI findings or presumed inheritance pattern. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ocular Health and Safety Assessment among Mechanics of the Cape Coast Metropolis, Ghana.

PubMed

Abu, Emmanuel Kwasi; Boadi-Kusi, Samuel Bert; Opuni, Prince Quarcoo; Kyei, Samuel; Owusu-Ansah, Andrew; Darko-Takyi, Charles

2016-01-01

To conduct an ocular health and safety assessment among mechanics in the Cape Coast Metropolis, Ghana. This descriptive cross sectional study included 500 mechanics using multistage sampling. All participants filled a structured questionnaire on demographic data, occupational history and ocular health history. Study participants underwent determination of visual acuity (VA) using LogMAR chart, external eye examination with a handheld slit lamp biomicroscope, dilated fundus examination, applanation tonometry and refraction. Out of 500 mechanics, 433 were examined (response rate, 87%) comprised of 408 (94.2%) male and 25 (5.8%) female subjects. The prevalence of visual impairment (i.e. presenting VA < 6/18) among the respondents was 2.1%. Eye injuries were reported in 171 (39.5%) mechanics probably due to the large number of workers, 314 (72.5%), who did not use eye protective devices. Mechanics in the auto welding category were at the highest risk of sustaining an eye injury (odds ratio [OR], 13.4; P < 0.001). Anterior segment ocular disorders were mostly pterygia while posterior segment eye disorders included glaucoma suspects and retinochoroidal lesions. The development of pterygia was associated with the number of years a mechanic stayed on the job. Eye care seeking behavior among the participants was poor. Eye injuries were prevalent among the mechanics as the use of eye protection was low. Eye safety should be made an integral part of the public health agenda in the Cape Coast Metropolis.

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

NASA Astrophysics Data System (ADS)

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

2010-01-01

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

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

USDA-ARS?s Scientific Manuscript database

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

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

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

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

Impact of Conjunctivochalasis on Visual Quality of Life: A Community Population Survey

PubMed Central

Xiang, Jun; Ge, Ling; Gong, Lan; Xu, Jianjiang

2014-01-01

Conjunctivochalasis (Cch) is a very common ocular disorder, which can cause an unstable tear film and ocular discomfort. The study of vision-related quality of life (VR-QoL) in a community population with Cch can provide a better understanding of the impact of Cch on common people than objective clinical examinations alone. This cross-sectional comparative study enrolled 360 participants ≥40 years old living in Sanle Community, Shanghai. In the study, 198 subjects were diagnosed with Cch and 86 with dry eye syndrome (DES) without Cch. The remaining 76 subjects were normal controls. Socio-demographical data were collected, and Cch and related ocular symptoms and signs were evaluated. In addition, all participants were required to complete the Chinese version of the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and Ocular Surface Disease Index Questionnaire (OSDI). Main outcome measures include the comparison on the OSDI score and VFQ-25 score among the subgroups, and the correlation of these scores with the socio-demographical and clinical data. The results revealed that subjects with Cch had significantly decreased tear film stability even compared with those with DES (P = 0.001). The participants with either Cch or DES reported significantly higher OSDI scores and lower VFQ-25 composite scores than the normal controls (P<0.001 and 0.007 respectively). Further comparisons among the subgroups of Cch revealed that the following factors were associated with higher OSDI scores and lower VFQ-25 composite scores: nasal-side Cch, chalasis folds higher than tear meniscus height, punctal occlusion, or increased extent of chalasis on digital pressure. In conclusion, Cch was associated with an adverse impact on VR-QoL in a community population, and the impairment in VR-QoL had a significant correlation with disease severity and tear film abnormalities. PMID:25330252

Impact of conjunctivochalasis on visual quality of life: a community population survey.

PubMed

Le, Qihua; Cui, Xinhan; Xiang, Jun; Ge, Ling; Gong, Lan; Xu, Jianjiang

2014-01-01

Conjunctivochalasis (Cch) is a very common ocular disorder, which can cause an unstable tear film and ocular discomfort. The study of vision-related quality of life (VR-QoL) in a community population with Cch can provide a better understanding of the impact of Cch on common people than objective clinical examinations alone. This cross-sectional comparative study enrolled 360 participants ≥ 40 years old living in Sanle Community, Shanghai. In the study, 198 subjects were diagnosed with Cch and 86 with dry eye syndrome (DES) without Cch. The remaining 76 subjects were normal controls. Socio-demographical data were collected, and Cch and related ocular symptoms and signs were evaluated. In addition, all participants were required to complete the Chinese version of the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) and Ocular Surface Disease Index Questionnaire (OSDI). Main outcome measures include the comparison on the OSDI score and VFQ-25 score among the subgroups, and the correlation of these scores with the socio-demographical and clinical data. The results revealed that subjects with Cch had significantly decreased tear film stability even compared with those with DES (P = 0.001). The participants with either Cch or DES reported significantly higher OSDI scores and lower VFQ-25 composite scores than the normal controls (P<0.001 and 0.007 respectively). Further comparisons among the subgroups of Cch revealed that the following factors were associated with higher OSDI scores and lower VFQ-25 composite scores: nasal-side Cch, chalasis folds higher than tear meniscus height, punctal occlusion, or increased extent of chalasis on digital pressure. In conclusion, Cch was associated with an adverse impact on VR-QoL in a community population, and the impairment in VR-QoL had a significant correlation with disease severity and tear film abnormalities.

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.

Ocular morbidity prevalence among school children in Shimla, Himachal, North India.

PubMed

Gupta, Madhu; Gupta, Bhupinder P; Chauhan, Anil; Bhardwaj, Ashok

2009-01-01

Data on eye diseases among school children is not readily available. Considering the fact that one-third of India's blind lose their eyesight before the age of 20 years and many of them are under five when they become blind, early detection and treatment of ocular morbidity among children is important. To estimate the prevalence of ocular morbidity among school children of age 6-16 years. Government and private coeducational schools in urban area of Shimla. Cross-sectional. Government and private coeducational schools selected by stratified random sampling. About 1561 school children, studying in elementary through secondary class in these schools were examined from August 2001 to January 2002 in Shimla. A doctor did visual acuity and detailed ophthalmic examination. The Chi-square test was used to test differences in proportions. Differences were considered to be statistically significant at the 5% level. Prevalence of ocular morbidity was 31.6% (CI=29.9-32.1%), refractive errors 22% (CI=21.1-22.8%), squint 2.5% (CI=2.4-2.6%), color blindness 2.3% (CI=2.2-2.4%), vitamin A deficiency 1.8 % (CI=1.7-1.9%), conjunctivitis 0.8% (CI=0.79-0.81%). Overall prevalence of ocular morbidity in government and private schools did not show any statistical significant difference. Prevalence of conjunctivitis was significantly (P< 0.5) more in government schools. A high prevalence of ocular morbidity among high-school children was observed. Refractive errors were the most common ocular disorders.

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.

Apremilast Use in a Case of Cicatricial Ectropion Secondary to Severe Lamellar Ichthyosis.

PubMed

Abboud, Jean-Paul J; Whittington, Alexander; Ahmed, Masih; Himebaugh, Jesse T; Wiley, Lee A; Haffar, Ahmad; Nguyen, John

Ichthyosis is a cutaneous disorder characterized by excessive amounts of dry thickened skin surface scales. Ocular manifestations of ichthyosis include cicatricial ectropion, which may cause exposure keratoconjunctivitis and rarely corneal perforation. Topical emollients, anti-inflammatory ointments, and systemic retinoids have been used to control the disease process, while surgical correction with donor graft has been reserved for severe cases involving corneal exposure. The authors report a case of a Caucasian male with lamellar ichthyosis with severe bilateral upper and lower eyelid cicatricial ectropion and corneal ulceration requiring surgical correction. Treatment with apremilast, a novel phosphodiesterase-4 inhibitor, for the treatment of a concomitant plaque psoriasis achieved good control of his skin diseases and minimized the recurrence of eyelid ectropion.

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

PubMed

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

2015-12-01

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

Influenza Virus Respiratory Infection and Transmission Following Ocular Inoculation in Ferrets

PubMed Central

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

2012-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

Ocular Stem Cell Research from Basic Science to Clinical Application: A Report from Zhongshan Ophthalmic Center Ocular Stem Cell Symposium

PubMed Central

Ouyang, Hong; Goldberg, Jeffrey L.; Chen, Shuyi; Li, Wei; Xu, Guo-Tong; Li, Wei; Zhang, Kang; Nussenblatt, Robert B.; Liu, Yizhi; Xie, Ting; Chan, Chi-Chao; Zack, Donald J.

2016-01-01

Stem cells hold promise for treating a wide variety of diseases, including degenerative disorders of the eye. The eye is an ideal organ for stem cell therapy because of its relative immunological privilege, surgical accessibility, and its being a self-contained system. The eye also has many potential target diseases amenable to stem cell-based treatment, such as corneal limbal stem cell deficiency, glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa (RP). Among them, AMD and glaucoma are the two most common diseases, affecting over 200 million people worldwide. Recent results on the clinical trial of retinal pigment epithelial (RPE) cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) in treating dry AMD and Stargardt’s disease in the US, Japan, England, and China have generated great excitement and hope. This marks the beginning of the ocular stem cell therapy era. The recent Zhongshan Ophthalmic Center Ocular Stem Cell Symposium discussed the potential applications of various stem cell types in stem cell-based therapies, drug discoveries and tissue engineering for treating ocular diseases. PMID:27102165

Age-Dependent Ocular Dominance Plasticity in Adult Mice

PubMed Central

Lehmann, Konrad; Löwel, Siegrid

2008-01-01

Background Short monocular deprivation (4 days) induces a shift in the ocular dominance of binocular neurons in the juvenile mouse visual cortex but is ineffective in adults. Recently, it has been shown that an ocular dominance shift can still be elicited in young adults (around 90 days of age) by longer periods of deprivation (7 days). Whether the same is true also for fully mature animals is not yet known. Methodology/Principal Findings We therefore studied the effects of different periods of monocular deprivation (4, 7, 14 days) on ocular dominance in C57Bl/6 mice of different ages (25 days, 90–100 days, 109–158 days, 208–230 days) using optical imaging of intrinsic signals. In addition, we used a virtual optomotor system to monitor visual acuity of the open eye in the same animals during deprivation. We observed that ocular dominance plasticity after 7 days of monocular deprivation was pronounced in young adult mice (90–100 days) but significantly weaker already in the next age group (109–158 days). In animals older than 208 days, ocular dominance plasticity was absent even after 14 days of monocular deprivation. Visual acuity of the open eye increased in all age groups, but this interocular plasticity also declined with age, although to a much lesser degree than the optically detected ocular dominance shift. Conclusions/Significance These data indicate that there is an age-dependence of both ocular dominance plasticity and the enhancement of vision after monocular deprivation in mice: ocular dominance plasticity in binocular visual cortex is most pronounced in young animals, reduced but present in adolescence and absent in fully mature animals older than 110 days of age. Mice are thus not basically different in ocular dominance plasticity from cats and monkeys which is an absolutely essential prerequisite for their use as valid model systems of human visual disorders. PMID:18769674

Fifteen-minute consultation-the child with a developmental disability: is there an ocular or visual abnormality?

PubMed

Salt, Alison; Sargent, Jenefer

2017-12-01

To present a structured approach for an outpatient consultation for a child with developmental disability who may have an ocular or visual disorder. Review of relevant literature and description of the approach to ocular and visual assessment which could be used by any paediatrician. A systematic approach to history, observation and examination of a child with a developmental disability will assist in identifying a possible visual problem. A structured referral letter will ensure that the child will receive the most appropriate assessment to clarify the problem and appropriate management in the eye clinic. © 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.

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

PubMed

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

2017-02-28

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

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

PubMed

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

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

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

PubMed

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

2003-10-01

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

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

PubMed

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

2017-01-01

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

Altered Mucin and Glycoprotein Expression in Dry Eye Disease.

PubMed

Stephens, Denise N; McNamara, Nancy A

2015-09-01

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

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

PubMed Central

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

2015-01-01

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

Man with a Swollen Eye: Nonspecific Orbital Inflammation in an Adult in the Emergency Department.

PubMed

Zhang, Xiao Chi; Statler, Brittney; Suner, Selim; Lloyd, Maureen; Curley, David; Migliori, Michael E

2018-07-01

Nonspecific orbital inflammation (NSOI) is a rare idiopathic ocular pathology characterized by unilateral, painful orbital swelling without identifiable infectious or systemic disorders, which can be complicated by optic nerve compromise. A 50-year-old man presented to the Emergency Department with recurring, progressive painless left eye swelling, decreased visual acuity, and binocular diplopia in the absence of trauma, infection, or known malignancy. His physical examination was notable for left-sided decreased visual acuity, an afferent pupillary defect, severe left eye proptosis and chemosis, and restricted extraocular movements; his dilatated funduscopic examination was notable for ipsilateral retinal folds within the macula, concerning for a disruption between the sclera and the retina. Ocular examination of the right eye was unremarkable. Laboratory data were unrevealing. Gadolinium-enhanced magnetic resonance imaging showed marked thickening of the left extraocular muscles associated with proptosis, dense inflammatory infiltration of the orbital fat, and characteristics consistent with perineuritis. The patient was diagnosed with NSOI with optic neuritis and admitted for systemic steroid therapy; he was discharged on hospital day 2 after receiving high-dose intravenous (i.v.) methylprednisolone with significant improvement. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: NSOI is a rare and idiopathic ocular emergency, with clinical mimicry resembling a broad spectrum of systemic diseases such as malignancy, autoimmune diseases, endocrine disorders, and infection. Initial work-up for new-onset ocular proptosis should include comprehensive laboratory testing and gadolinium-enhanced magnetic resonance imaging. Timely evaluation by an ophthalmologist is crucial to assess for optic nerve involvement. Signs of optic nerve compromise include decreased visual acuity, afferent pupillary defect, or decreased color saturation. Patients with optic nerve compromise require admission for aggressive anti-inflammatory therapy with i.v. steroids in an attempt to reduce risk of long-term visual sequelae. Our case demonstrates a severe presentation of this disorder and exhibits remarkable visual recovery after 48 h of systemic i.v. steroid treatment. Published by Elsevier Inc.

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.

Greater disruption to control of voluntary saccades in autistic disorder than Asperger's disorder: evidence for greater cerebellar involvement in autism?

PubMed

Stanley-Cary, Chloe; Rinehart, Nicole; Tonge, Bruce; White, Owen; Fielding, Joanne

2011-03-01

It remains unclear whether autism and Asperger's disorder (AD) exist on a symptom continuum or are separate disorders with discrete neurobiological underpinnings. In addition to impairments in communication and social cognition, motor deficits constitute a significant clinical feature in both disorders. It has been suggested that motor deficits and in particular the integrity of cerebellar modulation of movement may differentiate these disorders. We used a simple volitional saccade task to comprehensively profile the integrity of voluntary ocular motor behaviour in individuals with high functioning autism (HFA) or AD, and included measures sensitive to cerebellar dysfunction. We tested three groups of age-matched young males with normal intelligence (full scale, verbal, and performance IQ estimates >70) aged between 11 and 19 years; nine with AD, eight with HFA, and ten normally developing males as the comparison group. Overall, the metrics and dynamics of the voluntary saccades produced in this task were preserved in the AD group. In contrast, the HFA group demonstrated relatively preserved mean measures of ocular motricity with cerebellar-like deficits demonstrated in increased variability on measures of response time, final eye position, and movement dynamics. These deficits were considered to be consistent with reduced cerebellar online adaptation of movement. The results support the notion that the integrity of cerebellar modulation of movement may be different in AD and HFA, suggesting potentially differential neurobiological substrates may underpin these complex disorders.

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

[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.

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.

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.

Ocular Pseudoexfoliation and Cardiovascular Disease: A National Cross-Section Comparison Study

PubMed Central

French, Dustin D; Margo, Curtis E; Harman, Lynn E

2012-01-01

Background: Pseudoexfoliation is a systemic disorder characterized by the deposition of extracellular matrix material. The microfibrillar material that gives rise to the condition is visible clinically in the anterior segment of the eye, and is also found in other tissues, including blood vessels, skin, gallbladder, kidneys, lungs, and heart. Aims: The present study aims to determine whether ocular pseudoexfoliation is associated with selected cardiovascular diseases. Materials and Methods: A cross-section comparison study was conducted with the help of the Veterans Health Administration databases, using the International Classification of Diseases, Ninth revision, Clinical Modification for pseudoexfoliation of lens capsule and pseudoexfoliation glaucoma. Selected cardiovascular diseases and risk factors for cardiovascular disease were identified using the appropriate medical codes. Patients with primary open-angle glaucoma, chronic sinusitis, and benign prostatic hyperplasia served as the comparison groups. A logistic regression model was used to control for age, gender, race, and major cardiovascular risk factors. Results: There were 6,046 case patients with pseudoexfoliation; approximately half were diagnosed with pseudoexfoliation glaucoma. Various stages of ischemic heart disease, cardiomyopathy, and aortic aneurysm were significantly associated with ocular pseudoexfoliation, after controlling for age, gender, race, and major cardiovascular risk factors. Associations, in general, were less demonstrable relative to the primary open-angle glaucoma comparison group. Conclusion: Associations of ocular pseudoexfoliation with cardiovascular diseases were generally fewer and less pronounced when compared to patients with primary open-angle glaucoma. These results add to the results of earlier studies, which suggest that open-angle glaucoma itself might be a risk factor for certain cardiovascular disorders. PMID:23112968

Prevalence and severity of ocular involvement in Graves' disease according to sex and age: A clinical study from Babol, Iran.

PubMed

Gharib, Sara; Moazezi, Zoleika; Bayani, Mohammad Ali

2018-01-01

Thyroid-associated eye disease (TED), previously known as Graves' ophthalmopathy is a cosmetically and functionally debilitating disease that is seen worldwide. The aim of this study was to evaluate the prevalence and clinical severity of ocular manifestations of Graves' disease according to sex, age and duration in northern Iran. Between April 2011 and March 2012, 105 patients with Graves' disease, underwent ophthalmic examination, including ocular motility, exophthalmometry, intraocular pressure (IOP), slit lamp and fundoscopy. Patients received scores according to modified Werner's NO SPECS classification. Ocular involvement was found in 70 patients with established Graves's disease. The mean age was 35.0 years, (SD 13.0, range 15 to 69). The most common ocular findings were exophthalmometric proptosis of more than 20 mm (63.8%), lid lag (55.7%), lid retraction (52.8%) and tearing (38.6%). Almost 70% of patients had bilateral involvement. Elevated IOP was seen in 15 (25.4%) patients, and was significantly related to proptosis (P=0.007). More than half of the patients (n=36, 52.2%) had a modified Werner's NO SPECS score of 3.00. Clinical severity as shown by the increasing number of signs and symptoms per patient was correlated to increasing age (r=0.31, P=0.01) but not to gender (P=0.17). Both functional (ocular motility disorders, increased IOP) and cosmetic (proptosis, periorbital edema) sequels are common ocular presentations in patients with Graves' disease. Proptosis was the most common finding in this study and was associated with elevated IOP. Clinical severity was found to correlate to increasing age.

Contribution of laboratory methods in diagnosing clinically suspected ocular toxoplasmosis in Brazilian patients.

PubMed

Mattos, Cinara C B; Meira, Cristina S; Ferreira, Ana I C; Frederico, Fábio B; Hiramoto, Roberto M; Almeida, Gildásio C; Mattos, Luiz C; Pereira-Chioccola, Vera L

2011-07-01

This prospective study evaluated the value of laboratorial diagnosis in ocular toxoplasmosis analyzing peripheral blood samples from a group of Brazilian patients by immunologic and molecular methods. We analyzed blood samples from 184 immunocompetent patients with ocular disorders divided into 2 groups: Group I, composed of samples from 49 patients with ocular toxoplasmosis diagnosed by clinical features; Group II, samples from 135 patients with other ocular diseases. Samples were assayed by conventional polymerase chain reaction (cnPCR), real-time PCR (qPCR) for Toxoplasma gondii, indirect immunofluorescence reaction (IF), avidity test (crude tachyzoite lysate as antigen), and excreted-secreted tachyzoite proteins as antigen (ESA-ELISA). cnPCR and qPCR profiles were concordant in all samples. Positive PCR was shown in 40.8% of group I patients. The majority of the positive blood samples (75%) were taken from patients with toxoplasmic retinochoroiditis scars, and the others (25%), from patients with retinal exudative lesions. Despite that 86 of the 135 patients from Group II had asymptomatic toxoplasmosis, all DNA blood samples had negative PCR. Concordant results were shown in the data obtained by serologic methods. Around 24% of the patients with ocular toxoplasmosis had high antibody titers determined by ESA-ELISA and IF. Anti-ESA antibodies are shown principally in patients with active infection. Collectively, these data demonstrate the presence of tachyzoites in the blood of patients with chronic infection, supporting the idea of recurrent disease. Circulating parasites in blood of immunocompetent individuals may be associated with the reactivation of the ocular disease. Copyright © 2011 Elsevier Inc. All rights reserved.

Ocular morbidity prevalence among school children in Shimla, Himachal, North India

PubMed Central

Gupta, Madhu; Gupta, Bhupinder P; Chauhan, Anil; Bhardwaj, Ashok

2009-01-01

Background Data on eye diseases among school children is not readily available. Considering the fact that one-third of India's blind lose their eyesight before the age of 20 years and many of them are under five when they become blind, early detection and treatment of ocular morbidity among children is important. Aim To estimate the prevalence of ocular morbidity among school children of age 6-16 years. Settings Government and private coeducational schools in urban area of Shimla. Design Cross-sectional Materials and Methods Government and private coeducational schools selected by stratified random sampling. About 1561 school children, studying in elementary through secondary class in these schools were examined from August 2001 to January 2002 in Shimla. A doctor did visual acuity and detailed ophthalmic examination. Statistical analysis The Chi-square test was used to test differences in proportions. Differences were considered to be statistically significant at the 5% level. Results Prevalence of ocular morbidity was 31.6% (CI=29.9-32.1%), refractive errors 22% (CI=21.1-22.8%), squint 2.5% (CI=2.4-2.6%), color blindness 2.3% (CI=2.2-2.4%), vitamin A deficiency 1.8 % (CI=1.7-1.9%), conjunctivitis 0.8% (CI=0.79-0.81%). Overall prevalence of ocular morbidity in government and private schools did not show any statistical significant difference. Prevalence of conjunctivitis was significantly (P<0.5) more in government schools. Conclusion A high prevalence of ocular morbidity among high-school children was observed. Refractive errors were the most common ocular disorders. PMID:19237787

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

PubMed

Malik, Adeela; Claoué, Charles

2012-12-01

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

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

PubMed

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

2010-02-01

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

The Effects of Increasing Ocular Surface Stimulation on Blinking and Sensation

PubMed Central

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

2014-01-01

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

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.

Downbeat nystagmus due to ranitidine in a pediatric patient.

PubMed

Butragueño Laiseca, Laura; Toledo Del Castillo, Blanca; Rodríguez Jimenez, Cristina; Manrique-Rodríguez, Silvia; Pérez Moreno, Jimena

2017-07-01

Ranitidine has not been considered as a potential cause of ocular movement conditions. However, it is known that the vestibular nucleus complex, that has a key role in gaze control and vestibule-ocular reflexes, receives hypothalamic histaminergic innervations. Some studies reported the effect of ranitidine blocking the excitatory responses of vestibular nuclei neurons to histamine. We report the first case of a downbeat nystagmus secondary to ranitidine in an infant. A 3-month-old female developed a downbeat gaze after starting treatment with ranitidine for a pediatric gastroesophageal reflux disease. Microbiological test were negative and neuroblastoma evaluation was normal. As ranitidine is widely prescribed in the pediatric population, clinicians should be aware of its potential to cause ocular movements disorders. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Encephalocraniocutaneous lipomatosis with calvarial exostosis - Case report and review of literature

PubMed Central

Thakur, Shruti; Thakur, Vijay; Sood, Ram Gopal; Thakur, Charu Smita; Khanna, Shweta

2013-01-01

Encephalocraniocutaneous lipomatosis (ECCL), also known as Haberland syndrome, is a rare syndrome with unknown etiology. The syndrome is characterized by a triad of unique cutaneous, ocular, and central nervous system (CNS) manifestations. The cutaneous hallmark, nevus psiloliparus (NP), along with overlying alopecia is a constant feature. Choristoma of the eyelid is the most common ocular manifestation, while intracranial lipoma is the predominant CNS finding. Genetic counseling is required to emphasize that the disorder, although congenital, is not inheritable. We present a 21-year-old female with cutaneous, ocular, and CNS features satisfying the diagnostic criteria for ECCL. To our knowledge, this is the first case of ECCL having a large temporal exostosis. The objective of this article is to better understand the phenotypic spectrum of this syndrome whose molecular basis is still unknown. PMID:24604937

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.

Biologic Therapy for HLA-B27-associated Ocular Disorders.

PubMed

Gueudry, Julie; Thorne, Jennifer E; Bansie, Rakesh; Braun, Juergen; van Hagen, P Martin; Bodaghi, Bahram

2017-04-01

The treatment of articular and extra-articular manifestations associated with HLA-B27 has undergone dramatic changes over the past two decades, mainly as a consequence of the introduction of biologic agents and in particular anti-tumor necrosis factor α (anti-TNFα) agents. Uveitis is known to be the most frequent extra-articular feature in HLA-B27-associated spondyloarthritides. Topical corticosteroids and cycloplegic agents remain the cornerstones of treatment. However, biologic therapy may be effective in the management of refractory or recurrent forms of uveitis. This review gives an update on the management of HLA-B27-associated ocular disorders with biologics, including anti-TNFα agents and non-anti-TNFα biologic modifier drugs. There is an emerging role for newer biologics targeting interleukin-12/23 and interleukin-17 for the treatment of spondyloarthritides but data on their efficacy on anterior uveitis are sparse.

Multisegment coloboma in a case of Marfan syndrome: another possible effect of increased TGFβ signaling.

PubMed

LeBlanc, Shannon K; Taranath, Deepa; Morris, Scott; Barnett, Christopher P

2014-02-01

Colobomata are etiologically heterogeneous and may occur as an isolated defect or as a feature of a variety of single-gene disorders, chromosomal syndromes, or malformation syndromes. Although not classically associated with Marfan syndrome, colobomata have been described in several reports of Marfan syndrome, typically involving the lens and rarely involving other ocular structures. While colobomata of the lens have been described in Marfan syndrome, there are very few reports of coloboma involving other ocular structures. We report a newborn boy presenting with coloboma of the iris, lens, retina, and optic disk who was subsequently diagnosed with Marfan syndrome. Marfan syndrome is a disorder of increased TGFβ signaling, and recent work in the mouse model suggests a role for TGFβ signaling in eye development and coloboma formation, suggesting a causal association between Marfan syndrome and coloboma. Crown Copyright © 2014. Published by Mosby, Inc. All rights reserved.

Severe Ocular Inflammation Following Ranibizumab or Aflibercept Injections for Age-Related Macular Degeneration: A Retrospective Claims Database Analysis

PubMed Central

Souied, Eric H.; Dugel, Pravin U.; Ferreira, Alberto; Hashmonay, Ron; Lu, Jingsong; Kelly, Simon P.

2016-01-01

ABSTRACT Purpose: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents including ranibizumab and aflibercept are used to treat patients with ocular disorders such as neovascular age-related macular degeneration (nAMD); however, the injections are associated with rare instances of severe ocular inflammation. This study compared severe ocular inflammation rates in patients treated with ranibizumab versus aflibercept. Methods: United States physician-level claims data covering an 18-month period for each therapy were analyzed. The primary analysis compared severe ocular inflammation event rates per 1000 injections. Sensitivity and subgroup analyses evaluated the impact of factors including intraocular surgery, intravitreal antibiotic administration, and previous intravitreal injections. Results: The analysis included 432,794 injection claims (ranibizumab n = 253,647, aflibercept n = 179,147); significantly, more unique severe ocular inflammation events occurred in patients receiving aflibercept than ranibizumab (1.06/1000 injections, 95% confidence interval [CI], 0.91–1.21, vs. 0.64/1000 injections, 95% CI 0.54–0.74; p < 0.0001). Comparable results were observed for analyses of patients who had undergone glaucoma or cataract surgeries, had antibiotic-associated endophthalmitis, had non-antibiotic-associated endophthalmitis, and were non-treatment-naive. In contrast, no significant differences in severe ocular inflammation claims were recorded in treatment-naive patients who had no record of anti-VEGF treatment in the 6 months preceding the index claim. No significant change occurred in the rate of severe ocular inflammation claims over time following ranibizumab treatment. Conclusions: Severe ocular inflammation was more frequent following intravitreal injection with aflibercept than with ranibizumab during routine clinical use in patients with nAMD. This highlights the importance of real-world, post-approval, observational monitoring of novel medicines, and may aid clinical decision-making, including choice of anti-VEGF agent. PMID:26855278

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.

[Ocular cicatricial pemphigoid - state of the art in clinic and therapy for a problematic disease].

PubMed

Rübsam, A; Klein, J P; Pleyer, U

2013-08-01

The ocular cicatricial pemphigoid (OCP) belongs to a family of chronically progressive autoimmune disorders, predominantly affecting mucous membranes (mucous membrane pemphigoids). It is an immunopathologically heterogeneous group of disorders with variable phenotypes that share the unique feature of a subepidermal blistering, through disruption of the adhesion between epidermis and dermis. A key feature is the chronically active inflammation with consecutive fibrosis, leading to a partial or complete loss of function of the affected organ. The ocular disease as a chronic cicatrising conjunctivitis is a common manifestation of the mucous membrane pemphigoid. The identification of the subtle pathology and the prompt initiation of an appropriate therapy are of pivotal importance. One purpose is to prevent further vision loss due to extensive corneal scarring and life-threatening systemic complications, such as the formation of oesophageal or tracheal strictures. So far there are no prospective, randomised studies, regarding the therapy guidelines with an evidence level more than III. The autoimmune nature of the disease implies that systemic immunosuppression is the only effective treatment option, most notably in extended stages. The aim of our study is to give a guideline for a stage adjusted therapy with conventional immunosuppressants and to give a perspective for alternative therapies, especially for recalcitrant disease. Georg Thieme Verlag KG Stuttgart · New York.

IMAGE-GUIDED EVALUATION AND MONITORING OF TREATMENT RESPONSE IN PATIENTS WITH DRY EYE DISEASE

PubMed Central

Hamrah, Pedram

2014-01-01

Dry eye disease (DED) is one of the most common ocular disorders worldwide. The pathophysiological mechanisms involved in the development of DED are not well understood and thus treating DED has been a significant challenge for ophthalmologists. Most of the currently available diagnostic tests demonstrate low correlation to patient symptoms and have low reproducibility. Recently, sophisticated in vivo imaging modalities have become available for patient care, namely, in vivo confocal microscopy (IVCM) and optical coherence tomography (OCT). These emerging modalities are powerful and non-invasive, allowing real-time visualization of cellular and anatomical structures of the cornea and ocular surface. Here we discuss how, by providing both qualitative and quantitative assessment, these techniques can be used to demonstrate early subclinical disease, grade layer-by-layer severity, and allow monitoring of disease severity by cellular alterations. Imaging-guided stratification of patients may also be possible in conjunction with clinical examination methods. Visualization of subclinical changes and stratification of patients in vivo, allows objective image-guided evaluation of tailored treatment response based on cellular morphological alterations specific to each patient. This image-guided approach to DED may ultimately improve patient outcomes and allow studying the efficacy of novel therapies in clinical trials. PMID:24696045

Fast ray-tracing of human eye optics on Graphics Processing Units.

PubMed

Wei, Qi; Patkar, Saket; Pai, Dinesh K

2014-05-01

We present a new technique for simulating retinal image formation by tracing a large number of rays from objects in three dimensions as they pass through the optic apparatus of the eye to objects. Simulating human optics is useful for understanding basic questions of vision science and for studying vision defects and their corrections. Because of the complexity of computing such simulations accurately, most previous efforts used simplified analytical models of the normal eye. This makes them less effective in modeling vision disorders associated with abnormal shapes of the ocular structures which are hard to be precisely represented by analytical surfaces. We have developed a computer simulator that can simulate ocular structures of arbitrary shapes, for instance represented by polygon meshes. Topographic and geometric measurements of the cornea, lens, and retina from keratometer or medical imaging data can be integrated for individualized examination. We utilize parallel processing using modern Graphics Processing Units (GPUs) to efficiently compute retinal images by tracing millions of rays. A stable retinal image can be generated within minutes. We simulated depth-of-field, accommodation, chromatic aberrations, as well as astigmatism and correction. We also show application of the technique in patient specific vision correction by incorporating geometric models of the orbit reconstructed from clinical medical images. Copyright © 2014 Elsevier Ireland 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

Ultraviolet Radiation: Cellular Antioxidant Response and the Role of Ocular Aldehyde Dehydrogenase Enzymes

PubMed Central

Marchitti, Satori A.; Chen, Ying; Thompson, David C.; Vasiliou, Vasilis

2011-01-01

Solar ultraviolet radiation (UVR) exposes the human eye to near constant oxidative stress. Evidence suggests that UVR is the most important environmental insult leading to the development of a variety of ophthalmoheliosis disorders. UVR-induced reactive oxygen species are highly reactive with DNA, proteins and cellular membranes, resulting in cellular and tissue damage. Antioxidant defense systems present in ocular tissues function to combat reactive oxygen species and protect the eye from oxidative damage. Important enzymatic antioxidants are the superoxide dismutases, catalase, glutathione peroxidases, glutathione reductase and members of the aldehyde dehydrogenase (ALDH) superfamily. Glutathione, ascorbic and uric acids, α-tocopherol, NADPH and ferritin serve as small molecule, nonenzymatic antioxidants. Ocular tissues have high levels of these antioxidants which are essential for the maintenance of redox homeostasis in the eye and protection against oxidative damage. ALDH1A1 and ALDH3A1, present abundantly in the cornea and lens, have been shown to have unique roles in the defense against UVR and the downstream effects of oxidative stress. This review presents the properties and functions of ocular antioxidants that play critical roles in the cellular response to UVR exposure, including a focused discussion of the unique roles that the ALDH1A1 and ALDH3A1 enzymes have as multi-functional ocular antioxidants. PMID:21670692

Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression.

PubMed

Danno, Hiroki; Michiue, Tatsuo; Hitachi, Keisuke; Yukita, Akira; Ishiura, Shoichi; Asashima, Makoto

2008-04-08

The neural-related genes Sox2, Pax6, Otx2, and Rax have been associated with severe ocular malformations such as anophthalmia and microphthalmia, but it remains unclear as to how these genes are linked functionally. We analyzed the upstream signaling of Xenopus Rax (also known as Rx1) and identified the Otx2 and Sox2 proteins as direct upstream regulators of Rax. We revealed that endogenous Otx2 and Sox2 proteins bound to the conserved noncoding sequence (CNS1) located approximately 2 kb upstream of the Rax promoter. This sequence is conserved among vertebrates and is required for potent transcriptional activity. Reporter assays showed that Otx2 and Sox2 synergistically activated transcription via CNS1. Furthermore, the Otx2 and Sox2 proteins physically interacted with each other, and this interaction was affected by the Sox2-missense mutations identified in these ocular disorders. These results demonstrate that the direct interaction and interdependence between the Otx2 and Sox2 proteins coordinate Rax expression in eye development, providing molecular linkages among the genes responsible for ocular malformation.

The Gait Disorder in Downbeat Nystagmus Syndrome

PubMed Central

Schniepp, Roman; Wuehr, Max; Huth, Sabrina; Pradhan, Cauchy; Schlick, Cornelia; Brandt, Thomas; Jahn, Klaus

2014-01-01

Background Downbeat nystagmus (DBN) is a common form of acquired fixation nystagmus with key symptoms of oscillopsia and gait disturbance. Gait disturbance could be a result of impaired visual feedback due to the involuntary ocular oscillations. Alternatively, a malfunction of cerebellar locomotor control might be involved, since DBN is considered a vestibulocerebellar disorder. Methods Investigation of walking in 50 DBN patients (age 72±11 years, 23 females) and 50 healthy controls (HS) (age 70±11 years, 23 females) using a pressure sensitive carpet (GAITRite). The patient cohort comprised subjects with only ocular motor signs (DBN) and subjects with an additional limb ataxia (DBNCA). Gait investigation comprised different walking speeds and walking with eyes closed. Results In DBN, gait velocity was reduced (p<0.001) with a reduced stride length (p<0.001), increased base of support (p<0.050), and increased double support (p<0.001). Walking with eyes closed led to significant gait changes in both HS and DBN. These changes were more pronounced in DBN patients (p<0.001). Speed-dependency of gait variability revealed significant differences between the subgroups of DBN and DBNCA (p<0.050). Conclusions (I) Impaired visual control caused by involuntary ocular oscillations cannot sufficiently explain the gait disorder. (II) The gait of patients with DBN is impaired in a speed dependent manner. (III) Analysis of gait variability allows distinguishing DBN from DBNCA: Patients with pure DBN show a speed dependency of gait variability similar to that of patients with afferent vestibular deficits. In DBNCA, gait variability resembles the pattern found in cerebellar ataxia. PMID:25140517

The gait disorder in downbeat nystagmus syndrome.

PubMed

Schniepp, Roman; Wuehr, Max; Huth, Sabrina; Pradhan, Cauchy; Schlick, Cornelia; Brandt, Thomas; Jahn, Klaus

2014-01-01

Downbeat nystagmus (DBN) is a common form of acquired fixation nystagmus with key symptoms of oscillopsia and gait disturbance. Gait disturbance could be a result of impaired visual feedback due to the involuntary ocular oscillations. Alternatively, a malfunction of cerebellar locomotor control might be involved, since DBN is considered a vestibulocerebellar disorder. Investigation of walking in 50 DBN patients (age 72 ± 11 years, 23 females) and 50 healthy controls (HS) (age 70 ± 11 years, 23 females) using a pressure sensitive carpet (GAITRite). The patient cohort comprised subjects with only ocular motor signs (DBN) and subjects with an additional limb ataxia (DBNCA). Gait investigation comprised different walking speeds and walking with eyes closed. In DBN, gait velocity was reduced (p<0.001) with a reduced stride length (p<0.001), increased base of support (p<0.050), and increased double support (p<0.001). Walking with eyes closed led to significant gait changes in both HS and DBN. These changes were more pronounced in DBN patients (p<0.001). Speed-dependency of gait variability revealed significant differences between the subgroups of DBN and DBNCA (p<0.050). (I) Impaired visual control caused by involuntary ocular oscillations cannot sufficiently explain the gait disorder. (II) The gait of patients with DBN is impaired in a speed dependent manner. (III) Analysis of gait variability allows distinguishing DBN from DBNCA: Patients with pure DBN show a speed dependency of gait variability similar to that of patients with afferent vestibular deficits. In DBNCA, gait variability resembles the pattern found in cerebellar ataxia.

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.

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.

Orbital amelanotic melanoma in xeroderma pigmentosum: A rare association

PubMed Central

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

2008-01-01

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

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

PubMed

Korogiannaki, Myrto; Zhang, Jianfeng; Sheardown, Heather

2017-10-01

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

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

PubMed Central

Dartt, Darlene A.

2013-01-01

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

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

PubMed

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

2016-09-01

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

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

PubMed

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

2005-04-01

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

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

NASA Astrophysics Data System (ADS)

Pfeiffer, Karsten; Bendl, Rolf

2001-03-01

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

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

PubMed Central

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

2015-01-01

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

An increase in circulating B cell-activating factor in childhood-onset ocular myasthenia gravis.

PubMed

Motobayashi, Mitsuo; Inaba, Yuji; Nishimura, Takafumi; Kobayashi, Norimoto; Nakazawa, Yozo; Koike, Kenichi

2015-04-01

Myasthenia gravis is a B cell-mediated autoimmune disorder. The pathophysiology of childhood-onset ocular myasthenia gravis remains unclear. We investigated serum B cell-activating factor levels and other immunological parameters in child patients with ocular myasthenia gravis. Blood samples were obtained from 9 children with ocular myasthenia gravis and 20 age-matched controls. We assayed serum concentrations of B cell-activating factor, anti-acetylcholine receptor antibody titers, 7 types of cytokines (interleukins-2, -4, -6, -10, and -17A; interferon-γ; tumor necrosis factor-α) as well as the percentages of peripheral blood CD4+, CD8+, and CD19+ cells. Serum B cell-activating factor levels were significantly higher before immunosuppressive therapy in patients with childhood-onset ocular myasthenia gravis than in controls and decreased after immunosuppressive therapy. A significant positive correlation was observed between serum B cell-activating factor levels and anti-acetylcholine receptor antibody titers in patients with myasthenia gravis. Serum B cell-activating factor concentrations did not correlate with the percentages of CD4+, CD8+, and CD19+ cells or the CD4+/CD8+ ratio. No significant differences were observed in the levels of the 7 different types of cytokines examined, including interleukin-17A, between preimmunosuppressive therapy myasthenia gravis patients and controls. Circulating B cell-activating factor may play a key role in the pathophysiology of childhood-onset ocular myasthenia gravis. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel nanosystems for the treatment of ocular inflammation: Current paradigms and future research directions.

PubMed

Lalu, Lida; Tambe, Vishakha; Pradhan, Deepak; Nayak, Kritika; Bagchi, Suchandra; Maheshwari, Rahul; Kalia, Kiran; Tekade, Rakesh Kumar

2017-12-28

Ocular discomforts involve anterior/posterior-segment diseases, symptomatic distress and associated inflammations and severe retinal disorders. Conventionally, the formulations such as eye drops, eye solutions, eye ointments and lotions, etc. were used as modalities to attain relief from such ocular discomforts. However, eye allows limited access to these traditional formulations due to its unique anatomical structure and dynamic ocular environment and therefore calls for improvement in disease intervention. To address these challenges, development of nanotechnology based nanomedicines and novel nanosystems (liposomes, cubosomes, polymeric and lipidic nanoparticles, nanoemulsions, spanlastics and nano micelles) are currently in progress (some of them are already marketed such as Eye-logic liposomal eye spray@Naturalife, Ireland). Today, it is one of the central concept in designing more accessible formulations for deeper segments of the eyes. These nanosystems has largely enabled the availability of medicaments at required site in a required concentration without inversely affecting the eye tissues; and therefore, attaining the excessive considerations from the formulation scientists and pharmacologists worldwide. The entrapment of drugs, genes, and proteins inside these novel systems is the basis that works at the bio-molecular level bestows greater potential to eradicate disease causatives. In this review, we highlighted the recent attempts of nanotechnology-based systems for treating and managing various ocular ailments. The progress described herein may pave the way to new, highly effective and vital ocular nanosystems. Copyright © 2017. Published by Elsevier B.V.

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

PubMed

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

2018-07-01

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

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

PubMed

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

2015-04-01

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

Inflammation in dry eye.

PubMed

Stern, Michael E; Pflugfelder, Stephen C

2004-04-01

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

Juvenile xanthogranuloma of the corneoscleral limbus: case report and review of the literature.

PubMed

Chaudhry, Imtiaz A; Al-Jishi, Zohair; Shamsi, Farrukh A; Riley, Fenwick

2004-01-01

Juvenile xanthogranuloma is a benign histiocytic cutaneous disorder mainly occurring in infants which may affect the eye. Ocular manifestations usually present in the form of iris lesions with secondary hyphema and glaucoma, but juvenile xanthogranuloma may also present as a corneoscleral limbal mass. We present the case of an 18-month-old female infant with ocular juvenile xanthogranuloma occurring as a corneoscleral limbal mass without associated cutaneous or systemic findings. The limbal mass lesion was excised by lamellar dissection and histopathological studies revealed histiocytes admixed with lymphocytes, plasma cells, and eosinophils; foreign body and Touton giant cells present throughout the specimen confirmed the diagnosis of juvenile xanthogranuloma. At 14-month follow-up, there was no recurrence of the limbal mass. The natural history of this uncommon ocular condition is discussed and the relevant literature reviewed. Juvenile xanthogranuloma should be considered in the differential diagnosis of any corneoscleral limbal mass lesion, particularly in children.

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

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

Subterranean mammals show convergent regression in ocular genes and enhancers, along with adaptation to tunneling

PubMed Central

Partha, Raghavendran; Chauhan, Bharesh K; Ferreira, Zelia; Robinson, Joseph D; Lathrop, Kira; Nischal, Ken K

2017-01-01

The underground environment imposes unique demands on life that have led subterranean species to evolve specialized traits, many of which evolved convergently. We studied convergence in evolutionary rate in subterranean mammals in order to associate phenotypic evolution with specific genetic regions. We identified a strong excess of vision- and skin-related genes that changed at accelerated rates in the subterranean environment due to relaxed constraint and adaptive evolution. We also demonstrate that ocular-specific transcriptional enhancers were convergently accelerated, whereas enhancers active outside the eye were not. Furthermore, several uncharacterized genes and regulatory sequences demonstrated convergence and thus constitute novel candidate sequences for congenital ocular disorders. The strong evidence of convergence in these species indicates that evolution in this environment is recurrent and predictable and can be used to gain insights into phenotype–genotype relationships. PMID:29035697

Characterization of the pH and Temperature in the Rabbit, Pig, and Monkey Eye: Key Parameters for the Development of Long-Acting Delivery Ocular Strategies.

PubMed

Lorget, Florence; Parenteau, Audrey; Carrier, Michel; Lambert, Daniel; Gueorguieva, Ana; Schuetz, Chris; Bantseev, Vlad; Thackaberry, Evan

2016-09-06

Many long-acting delivery strategies for ocular indications rely on pH- and/or temperature-driven release of the therapeutic agent and degradation of the drug carrier. Yet, these physiological parameters are poorly characterized in ocular animal models. These strategies aim at reducing the frequency of dosing, which is of particular interest for the treatment of chronic disorders affecting the posterior segment of the eye, such as macular degeneration that warrants monthly or every other month intravitreal injections. We used anesthetized white New Zealand rabbits, Yucatan mini pigs, and cynomolgus monkeys to characterize pH and temperature in several vitreous locations and the central aqueous location. We also established post mortem pH changes in the vitreous. Our data showed regional and species differences, which need to be factored into strategies for developing biodegradable long-acting delivery systems.

Ataxia telangiectasia: learning from previous mistakes

PubMed Central

Kumar, Naveen; Aggarwal, Puneet; Dev, Nishanth; kumar, Gunjan

2012-01-01

Ataxia telangiectasia is an early onset neurodegenerative disorder. We report a case of childhood onset ataxia and ocular telangiectasia, presenting with pulmonary infection. The patient was diagnosed as ataxia telangiectasia. The patient succumbed to death owing to late diagnosis and sepsis. PMID:23242084

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.

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.

Referral patterns to an ophthalmic outpatient clinic by general practitioners and ophthalmic opticians and the role of these professionals in screening for ocular disease.

PubMed

Harrison, R J; Wild, J M; Hobley, A J

1988-11-05

Case notes of 1113 consecutive new patients referred to a consultant ophthalmologist at a district general hospital were reviewed to determine the source and efficacy of referrals and the current screening practices of general practitioners and ophthalmic opticians. General practitioners initiated referral in 546 cases (49%) and ophthalmic opticians referral in 439 (39%). Visual loss or visual disturbance was the most important single reason for referral (345 cases; 31%), followed by suspected glaucoma (145 cases; 13%), abnormalities of binocular vision (140; 12.5%), disorders of eyelids or ocular adnexa (127; 11%), and red eye (86; 8%). General practitioners referred many more patients with disorders of the eyelids and adnexa and ophthalmic opticians many more patients with suspected glaucoma. Ophthalmic opticians were far more likely than general practitioners to refer patients with suspected glaucoma correctly. A total of 180 patients (16%) were referred from ocular screening, in 149 cases by ophthalmic opticians and in 10 by general practitioners. Seventy patients had glaucoma or incomplete features of glaucoma, all of them referred by ophthalmic opticians. Of eight diabetic patients referred by ophthalmic opticians, three had asymptomatic disease and in two diabetes was diagnosed as a result of ocular screening. No patient was referred for asymptomatic diabetic retinopathy from screening by general practitioners. Ophthalmic opticians were more likely than general practitioners to diagnose retinopathy requiring photocoagulation. Use of a community based service to screen for glaucoma could save unnecessary consultant outpatient appointments. A similar service could facilitate detection of diabetic retinopathy at a stage when treatment is most effective.

Referral patterns to an ophthalmic outpatient clinic by general practitioners and ophthalmic opticians and the role of these professionals in screening for ocular disease.

PubMed Central

Harrison, R. J.; Wild, J. M.; Hobley, A. J.

1988-01-01

Case notes of 1113 consecutive new patients referred to a consultant ophthalmologist at a district general hospital were reviewed to determine the source and efficacy of referrals and the current screening practices of general practitioners and ophthalmic opticians. General practitioners initiated referral in 546 cases (49%) and ophthalmic opticians referral in 439 (39%). Visual loss or visual disturbance was the most important single reason for referral (345 cases; 31%), followed by suspected glaucoma (145 cases; 13%), abnormalities of binocular vision (140; 12.5%), disorders of eyelids or ocular adnexa (127; 11%), and red eye (86; 8%). General practitioners referred many more patients with disorders of the eyelids and adnexa and ophthalmic opticians many more patients with suspected glaucoma. Ophthalmic opticians were far more likely than general practitioners to refer patients with suspected glaucoma correctly. A total of 180 patients (16%) were referred from ocular screening, in 149 cases by ophthalmic opticians and in 10 by general practitioners. Seventy patients had glaucoma or incomplete features of glaucoma, all of them referred by ophthalmic opticians. Of eight diabetic patients referred by ophthalmic opticians, three had asymptomatic disease and in two diabetes was diagnosed as a result of ocular screening. No patient was referred for asymptomatic diabetic retinopathy from screening by general practitioners. Ophthalmic opticians were more likely than general practitioners to diagnose retinopathy requiring photocoagulation. Use of a community based service to screen for glaucoma could save unnecessary consultant outpatient appointments. A similar service could facilitate detection of diabetic retinopathy at a stage when treatment is most effective. PMID:3144331

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.

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.

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

[Preimplantation genetic diagnosis and monogenic inherited eye diseases].

PubMed

Hlavatá, L; Ďuďáková, Ľ; Trková, M; Soldátová, I; Skalická, P; Kousal, B; Lišková, P

Preimplantation genetic diagnosis (PGD) is an established application of genetic testing in the context of in vitro fertilization. PGD is an alternative method to prenatal diagnosis which aims to prevent the transmission of an inherited disorder to the progeny by implanting only embryos that do not carry genetic predisposition for a particular disease. The aim of this study is to provide an overview of eye disorders for which PGD has been carried out. The European literature search focused on best practices, ethical issues, risks and results of PGD for inherited eye disorders. PGD is performed for a number of ocular disorders; a prerequisite for its application is however, the knowledge of a disease-causing mutation(s). The main advantage of this method is that the couple is not exposed to a decision of whether or not to undergo an abortion. Qualified counselling must be provided prior to the PGD in order to completely understand the risk of disability in any child conceived, consequences of disease manifestation, and advantages as well as limitations of this method. In the group of non-syndromic eye diseases and diseases in which ocular findings dominate, PGD has been performed in European countries for aniridia, choroideremia, congenital fibrosis of extraocular muscles, Leber congenital amaurosis, ocular albinism, retinitis pigmentosa, X-linked retinoschisis, Stargardt disease, blepharophimosis-ptosis-inverse epicanthus syndrome and retinoblastoma. Sexing for X-linked or mitochondrial diseases has been carried out for blue cone monochromatism, choroideremia, familial exudative vitreoretinopathy, Leber hereditary optic neuropathy, macular dystrophy (not further specified), Norrie disease, X-linked congenital stationary night blindness, X-linked retinoschisis and nystagmus (not further specified). In recent years, there has been an increase in potential to use PGD. The spectrum of diseases for this method has widened to include severe inherited eye diseases.Key words: preimplantation genetic diagnosis; monogenic eye diseases; in vitro fertilization.

Assessment of ocular toxoplasmosis patients reported at a tertiary center in the northeast of Iran.

PubMed

Hosseini, Seyedeh Maryam; Moghaddas, Elham; Sharifi, Karim; Dadgar Moghaddam, Malihe; Shamsian, Seyed Aliakbar

2018-01-15

Ocular toxoplasmosis, which is caused by the single-cell parasite Toxoplasma gondii, is currently the most significant cause of posterior uveitis in the world. No previous studies have described the prevalence and clinical features of ocular toxoplasmosis in the northeast of Iran. The purpose of the current study was to address this gap. In this retrospective study, the medical records of 488 uveitis patients who presented to the Khatam-al-Anbia Eye Hospital of Mashhad University of Medical Sciences, a tertiary ophthalmology center in the northeast of Iran, between January 2013 and December 2015 were evaluated. The clinical features and risk factors of 99 (20%) consecutive patients with ocular toxoplasmosis were extracted. Ninety-nine including 53 (53.5%) female and 46 (46.5%) male patients with ocular toxoplasmosis were included in the analysis. Reduced vision (77%) and floaters (15.2%) were the most common presenting symptoms. The age category that was most affected by ocular toxoplasmosis was 20-40 years (range: 11-65 years) with a mean age of 27.2. All patients had retinochoroiditis, but just two had anterior uveitis. All of the extracted patients, with the exception of three patients, had unilateral involvement. None of the patients had any other medical disorders with the exception of one woman, who had diabetes. Only four recurring ocular toxoplasmosis patients were referred to the education hospital during the study. Serology data were available for just 32 patients, of which 31 (96.8%) were IgG positive, and 1 (3.2%) was IgM positive. Toxoplasma gondii was responsible for 20% of the patients of uveitis that presented to the largest ophthalmology center in the northeast of Iran. There is a high incidence of patients of ocular toxoplasmosis in the northeast of Iran, and it is a significant cause of uveitis and visual impairment in this area.

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.

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

PubMed

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

2015-01-01

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

Dry Eye: an Inflammatory Ocular Disease

PubMed Central

Hessen, Michelle; Akpek, Esen Karamursel

2014-01-01

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

Cerebral palsy characterization by estimating ocular motion

NASA Astrophysics Data System (ADS)

González, Jully; Atehortúa, Angélica; Moncayo, Ricardo; Romero, Eduardo

2017-11-01

Cerebral palsy (CP) is a large group of motion and posture disorders caused during the fetal or infant brain development. Sensorial impairment is commonly found in children with CP, i.e., between 40-75 percent presents some form of vision problems or disabilities. An automatic characterization of the cerebral palsy is herein presented by estimating the ocular motion during a gaze pursuing task. Specifically, After automatically detecting the eye location, an optical flow algorithm tracks the eye motion following a pre-established visual assignment. Subsequently, the optical flow trajectories are characterized in the velocity-acceleration phase plane. Differences are quantified in a small set of patients between four to ten years.

Varicella Zoster Complications

PubMed Central

Nagel, Maria A.; Gilden, Don

2013-01-01

Opinion statement Varicella zoster virus (VZV) is an exclusively human neurotropic alphaherpesvirus. Primary infection causes varicella (chickenpox), after which virus becomes latent in ganglionic neurons along the entire neuraxis. With advancing age or immunosuppression, cell-mediated immunity to VZV declines and virus reactivates to cause zoster (shingles), which can occur anywhere on the body. Skin lesions resolve within 1-2 weeks, while complete cessation of pain usually takes 4-6 weeks. Zoster can be followed by chronic pain (postherpetic neuralgia), cranial nerve palsies, zoster paresis, meningoencephalitis, cerebellitis, myelopathy, multiple ocular disorders and vasculopathy that can mimic giant cell arteritis. All of the neurological and ocular disorders listed above may also develop without rash. Diagnosis of VZV-induced neurological disease may require examination of CSF, serum and/ or ocular fluids. In the absence of rash in a patient with neurological disease potentially due to VZV, CSF should be examined for VZV DNA by PCR and for anti-VZV IgG and IGM. Detection of VZV IgG antibody in CSF is superior to detection of VZV DNA in CSF to diagnose vasculopathy, recurrent myelopathy, and brainstem encephalitis. Oral antiviral drugs speed healing of rash and shorten acute pain. Immunocompromised patients require intravenous acyclovir. First-line treatments for post-herpetic neuralgia include tricyclic antidepressants gabapentin, pregabalin, and topical lidocaine patches. VZV vasculopathy, meningoencephalitis, and myelitis are all treated with intravenous acyclovir. PMID:23794213

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

PubMed

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

2010-01-01

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

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

PubMed

Rolle, Teresa; Spinetta, Roberta; Nuzzi, Raffaele

2017-08-03

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

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

PubMed

Papas, Eric B; Sweeney, Deborah F

2016-10-01

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

Gene Therapy in the Cornea: 2005-present

PubMed Central

Mohan, Rajiv R.; Tovey, Jonathan C.K.; Sharma, Ajay; Tandon, Ashish

2011-01-01

Successful restoration of vision in human patients with gene therapy affirmed its promise to cure ocular diseases and disorders. The efficacy of gene therapy is contingent upon vector and mode of therapeutic DNA introduction into targeted cells/tissues. The cornea is an ideal tissue for gene therapy due to its ease of access and relative immune-privilege. Considerable progress has been made in the field of corneal gene therapy in last 5 years. Several new gene transfer vectors, techniques and approaches have evolved. Although corneal gene therapy is still in its early stages of development, the potential of gene-based interventions to treat corneal abnormalities have begun to surface. Identification of next generation viral and nanoparticle vectors, characterization of delivered gene levels, localization, and duration in the cornea, and significant success in controlling corneal disorders, particularly fibrosis and angiogenesis, in experimental animal disease models, with no major side effects have propelled gene therapy a step closer towards establishing gene-based therapies for corneal blindness. Recently, researchers have assessed the delivery of therapeutic genes for corneal diseases and disorders due to trauma, infections, chemical, mechanical, and surgical injury, and/or abnormal wound healing. This review provides an update on the developments in gene therapy for corneal diseases and discusses the barriers that hinder its utilization for delivering genes in the cornea. PMID:21967960

Molecular links among the causative genes for ocular malformation: Otx2 and Sox2 coregulate Rax expression

PubMed Central

Danno, Hiroki; Michiue, Tatsuo; Hitachi, Keisuke; Yukita, Akira; Ishiura, Shoichi; Asashima, Makoto

2008-01-01

The neural-related genes Sox2, Pax6, Otx2, and Rax have been associated with severe ocular malformations such as anophthalmia and microphthalmia, but it remains unclear as to how these genes are linked functionally. We analyzed the upstream signaling of Xenopus Rax (also known as Rx1) and identified the Otx2 and Sox2 proteins as direct upstream regulators of Rax. We revealed that endogenous Otx2 and Sox2 proteins bound to the conserved noncoding sequence (CNS1) located ≈2 kb upstream of the Rax promoter. This sequence is conserved among vertebrates and is required for potent transcriptional activity. Reporter assays showed that Otx2 and Sox2 synergistically activated transcription via CNS1. Furthermore, the Otx2 and Sox2 proteins physically interacted with each other, and this interaction was affected by the Sox2-missense mutations identified in these ocular disorders. These results demonstrate that the direct interaction and interdependence between the Otx2 and Sox2 proteins coordinate Rax expression in eye development, providing molecular linkages among the genes responsible for ocular malformation. PMID:18385377

Diabetic corneal neuropathy: clinical perspectives.

PubMed

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

2018-01-01

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

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

PubMed

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

2007-01-01

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

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

PubMed

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

2009-08-01

We designed a randomized, double blinded, 3-months controlled prospective clinical study to investigate effects of oral uridine on the ocular surface in dry eye patients. Twenty-seven patients who diagnosed as dry eye with lower than 5 mm of wetting in the Schirmer strip, with corneal epithelial erosion and who completely followed-up till 3 months were enrolled. Corneal-conjunctival fluorescein staining, non-anesthetic Schirmer test, impression cytology, and Ocular Surface Disease Index (OSDI) were evaluated in the experimental and placebo groups at the baseline, 1 and 3 months after start of medication in a double blinded manner. Fluorescein stain score of the cornea was markedly decreased in oral uridine group compared to the placebo group at 3 months after medication (P=0.032, Mann-Whitney U test). The Schirmer wetting score for the oral uridine group was significantly increased (P=0.001, Wilcoxon signed rank test) at 3 months and its difference between two groups was statistically significant (P=0.030, Mann-Whitney U test). OSDI scores were significantly decreased at 1 and 3 months in treatment group. Oral uridine is effective in treatment of dry eyes.

Ocular surface changes in thyroid eye disease.

PubMed

Ismailova, Dilyara S; Fedorov, Anatoly A; Grusha, Yaroslav O

2013-04-01

To study the incidence and risk factors of ocular surface damage in thyroid eye disease (TED) and to determine histological changes underlying positive vital staining in this condition. Forty-six patients (92 eyes) with TED were included in this study. Routine ophthalmologic examination, Schirmer test I, vital staining and corneal sensitivity were performed. Fifteen patients with positive vital staining underwent impression cytology and incisional biopsy. Positive vital staining with lissamine green was observed in 56 eyes (60.9%), 30 patients (65.2%). The average degree of staining was 4.57 ± 0.44 (National Eye Institute Workshop grading system). Severe dry eye syndrome was found in 16%. The following histological changes of conjunctiva were revealed: significant epithelial dystrophy with cell polymorphism, goblet cells loss, excessive desquamation and epithelial keratinization with local leukocytic infiltration of substantia propria. According to our results dry eye syndrome is present in 65.2% of patients (60.9% eyes) with TED. Significant risk factors of ocular surface damage in TED were exophthalmos, lagophthalmos, palpebral fissure height and lower lid retraction. Positive conjunctival staining results from punctuate epithelial erosions and excessive desquamation of superficial cells. Histopathologic changes detected in conjunctiva consistent with dry eye and are not specific for TED.

Biopharmaceutical profile of pranoprofen-loaded PLGA nanoparticles containing hydrogels for ocular administration.

PubMed

Abrego, Guadalupe; Alvarado, Helen; Souto, Eliana B; Guevara, Bessy; Bellowa, Lyda Halbaut; Parra, Alexander; Calpena, Ana; Garcia, María Luisa

2015-09-01

Two optimized pranoprofen-loaded poly-l-lactic-co glycolic acid (PLGA) nanoparticles (PF-F1NPs; PF-F2NPs) have been developed and further dispersed into hydrogels for the production of semi-solid formulations intended for ocular administration. The optimized PF-NP suspensions were dispersed in freshly prepared carbomer hydrogels (HG_PF-F1NPs and HG_PF-F2NPs) or in hydrogels containing 1% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone) in order to improve the ocular biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (NSAID), by prolonging the contact of the pranoprofen with the eye, increasing the drug retention in the organ and enhancing its anti-inflammatory and analgesic efficiency. Carbomer 934 has been selected as gel-forming polymer. The hydrogel formulations with or without azone showed a non-Newtonian behavior and adequate physicochemical properties for ocular instillation. The release study of pranoprofen from the semi-solid formulations exhibited a sustained release behavior. The results obtained from ex vivo corneal permeation and in vivo anti-inflammatory efficacy studies suggest that the ocular application of the hydrogels containing azone was more effective over the azone-free formulations in the treatment of edema on the ocular surface. No signs of ocular irritancy have been detected for the produced hydrogels. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinical applications of fundus autofluorescence in retinal disease.

PubMed

Yung, Madeline; Klufas, Michael A; Sarraf, David

2016-01-01

Fundus autofluorescence (FAF) is a non-invasive retinal imaging modality used in clinical practice to provide a density map of lipofuscin, the predominant ocular fluorophore, in the retinal pigment epithelium. Multiple commercially available imaging systems, including the fundus camera, the confocal scanning laser ophthalmoscope, and the ultra-widefield imaging device, are available to the clinician. Each offers unique advantages for evaluating various retinal diseases. The clinical applications of FAF continue to expand. It is now an essential tool for evaluating age related macular degeneration, macular dystrophies, retinitis pigmentosa, white dot syndromes, retinal drug toxicities, and various other retinal disorders. FAF may detect abnormalities beyond those detected on funduscopic exam, fluorescein angiography, or optical coherence tomography, and can be used to elucidate disease pathogenesis, form genotype-phenotype correlations, diagnose and monitor disease, and evaluate novel therapies. Given its ease of use, non-invasive nature, and value in characterizing retinal disease, FAF enjoys increasing clinical relevance. This review summarizes common ocular fluorophores, imaging modalities, and FAF findings for a wide spectrum of retinal disorders.

Allergic manifestations of contact lens wearing.

PubMed

Solomon, Abraham

2016-10-01

Contact lens-induced papillary conjunctivitis (CLPC) is a common ocular allergic disease in contact lens wearers. In its more severe form, it can cause giant papillary conjunctivitis, resulting in contact lens intolerance and the need to discontinue the use of contact lenses. This review presents the pathogenesis, clinical manifestations and management guidelines of this common disorder. Different types of contact lenses are associated with differences in the severity of CLPC. Refitting patients with silicone hydrogel contact lenses or with daily disposable contact lenses may improve the signs and symptoms of CLPC. The recent introduction of the topical immunomodulatory agent tacrolimus in other severe allergic eye diseases may apply in suppressing the allergic inflammation in CLPC as well. CLPC is a common ocular disorder in contact lens wearers, with a significant impact on the quality of vision. It should be promptly recognized by healthcare practitioners and managed by modifications of the types and wearing schedules of contact lenses, as well as novel treatment options with topical immunomodulators.

Resveratrol and Ophthalmic Diseases

PubMed Central

Abu-Amero, Khaled K.; Kondkar, Altaf A.; Chalam, Kakarla V.

2016-01-01

Resveratrol, a naturally occurring plant polyphenol found in grapes, is the principal biologically active component in red wine. Clinical studies have shown that resveratrol due to its potent anti-oxidant and anti-inflammatory properties are cardio-protective, chemotherapeutic, neuroprotective, and display anti-aging effects. Oxidative stress and inflammation play a critical role in the initiation and progression of age-related ocular diseases (glaucoma, cataract, diabetic retinopathy and macular degeneration) that lead to progressive loss of vision and blindness. In vitro and in vivo (animal model) experimental studies performed so far have provided evidence for the biological effects of resveratrol on numerous pathways including oxidative stress, inflammation, mitochondrial dysfunction, apoptosis, pro-survival or angiogenesis that are implicated in the pathogenesis of these age-related ocular disorders. In this review, we provide a brief overview of current scientific literature on resveratrol, its plausible mechanism(s) of action, its potential use and current limitations as a nutritional therapeutic intervention in the eye and its related disorders. PMID:27058553

[Transplantation of autologous labial salivary glands for severe dry eye].

PubMed

Luo, Shun-rong; Zou, Liu-he; Yan, Chao; Pan, Zhi-qiang; Liu, Jing-ming; Chen, Zhi-yuan; Yin, Wei-hong

2013-01-01

Autologous labial salivary gland transplantation has been a promising alternative for the treatment of severe dry eye. In this article, we describe the results of the ocular surface changes after labial salivary gland transplantation and investigate the feasibility of this treatment. The results of this technique in 8 patients (eyes) who suffered from severe dry eye were prospectively analyzed after surgery (follow-up of 6 months). The best-corrected visual acuity, Schirmer I test, degree of discomfort, usage of pharmaceutical tear substitutes, tear interferometry and slit lamp examination were investigated at different time before and after surgery. All grafts remained viable and the survival rate is 100%. All patients showed significant increase in the Schirmer's test and they expressed great improvement in their ocular discomfort. The use of artificial tear substitutes was reduced because of the increased ocular surface lubrication. Although the authors' long-term experience still is limited, we believe that the procedure is a promising alternative approach for severe dry eye.

Dry Eye Syndrome in Menopause and Perimenopausal Age Group.

PubMed

Peck, Travis; Olsakovsky, Leslie; Aggarwal, Shruti

2017-01-01

Dry eye disease (DED) is a multifactorial ocular surface disease that causes symptoms of ocular pain, discomfort, and decreased visual acuity. It significantly affects quality of life of patients. It is more prevalent in the females and is being specifically in the menopausal and postmenopausal age group. This is believed to be due to the changes in balance of sex hormones. Sex hormones - estrogens and androgens - influence production of all components of the tear film including aqueous layer, lipid, and mucin. Various mechanisms such as decrease in hormonal levels, shift in feedback mechanisms, and changes in receptor receptivity interplay to alter the ocular surface homeostasis and subsequently result in DED. Several studies have suggested potential role of hormone replacement therapy in menopause-associated dry eye symptoms. The purpose of this review is to help the non ophthalmic physicians about DED encountered commonly in menopausal age group. It is important for primary care physicians to understand DED due to its high prevalence, often debilitating symptoms and the potentially preventable and treatable nature of the condition.

Impact of Eye Cosmetics on the Eye, Adnexa, and Ocular Surface.

PubMed

Ng, Alison; Evans, Katharine; North, Rachel V; Jones, Lyndon; Purslow, Christine

2016-07-01

Despite the fact that cosmetic products undergo rigorous testing to ensure they are safe for human use, some users report mild discomfort following their application. The cutaneous changes, such as allergic dermatitis, are well reported, but the ocular changes associated with eye cosmetic use are less so. Some pigmented cosmetic products may accumulate within the lacrimal system and conjunctivae over many years of use, but immediate reports of eye discomfort after application are most common. Changes to the tear film and its stability may occur shortly after application, and contact lens wearers can also be affected by lens spoliation from cosmetic products. Additionally, creams used in the prevention of skin aging are often applied around the eyes, and retinoids present in these formulations can have negative effects on meibomian gland function and may be a contributing factor to dry eye disease. The aim of this review is to summarize current knowledge regarding the impact of cosmetic products on the eye, ocular surface, and tear film.

Novel surface-modified nanostructured lipid carriers with partially deacetylated water-soluble chitosan for efficient ocular delivery.

PubMed

Tian, Baocheng; Luo, Qiuhua; Song, Shuangshuang; Liu, Dandan; Pan, Hao; Zhang, Wenji; He, Ling; Ma, Shilin; Yang, Xinggang; Pan, Weisan

2012-03-01

The objective of this study was to propose novel surface-modified nanostructured lipid carriers with partially deacetylated water-soluble chitosan (NLC-PDSC) as an efficient ocular delivery system to improve its transcorneal penetration and precorneal retention. PDSC with a deacetylation degree of around 50% was synthesized using an improved method. NLC loaded with flurbiprofen (FB) were prepared by melt emulsification method. They presented spherical morphology under both transmission electron microscope and scanning electron microscope. After coating with 0.15% (w/v) PDSC solution, the NLC showed a core-shell structure and a reversed zeta potential. The enhanced transcorneal penetration of the coated NLC was evaluated using isolated rabbit corneas, with significantly increased apparent permeability coefficient being 1.40- and 1.75-fold of the NLC and FB phosphate solution (FB-sol; p < 0.05), respectively. Precorneal retention assessed by gamma scintigraphy in vivo showed that the area under the remaining activity-time curve of the PDSC-coated formulation was 1.3-fold of the NLC and 2.4-fold of FB-sol. Moreover, in vivo ocular tolerance study indicated that there was no difference in irritation between the coated and noncoated NLC. In conclusion, novel NLC demonstrate high potential for ocular drug delivery. Copyright © 2011 Wiley Periodicals, Inc.

Implantation of refractive multifocal intraocular lens with a surface-embedded near section for cataract eyes complicated with a coexisting ocular pathology

PubMed Central

Ouchi, M; Kinoshita, S

2015-01-01

Purpose To evaluate the postoperative outcomes of cataract eyes complicated with coexisting ocular pathologies that underwent implantation of a refractive multifocal intraocular lens (MIOL) with a surface-embedded near section. Methods LENTIS MPlus (Oculentis GmbH) refractive MIOLs were implanted in 15 eyes with ocular pathologies other than cataract (ie, six high-myopia eyes with an axial length longer than 28 mm, two fundus albipunctatus eyes, two branch retinal-vein occlusion eyes, four glaucoma eyes (one with high myopia), and two keratoconus eyes). Uncorrected or corrected distance and near visual acuity (VA) (UDVA, UNVA, CDVA, and CNVA), contrast sensitivity, and defocus curve were measured at 1 day and 6 months postoperatively, and each patient completed a 6-month postoperative questionnaire regarding vision quality and eyeglass use. Results Thirteen eyes (87%) registered 0 or better in CDVA and 12 eyes (73%) registered better than 0 in CNVA. Contrast sensitivity in the eyes of all patients was comparable to that of normal healthy subjects. No patient required eyeglasses for distance vision, but three patients (20%) required them for near vision. No patient reported poor or very poor vision quality. Conclusion With careful case selection, sectorial refractive MIOL implantation is effective for treating cataract eyes complicated with ocular pathologies. PMID:25744442

Implantation of refractive multifocal intraocular lens with a surface-embedded near section for cataract eyes complicated with a coexisting ocular pathology.

PubMed

Ouchi, M; Kinoshita, S

2015-05-01

To evaluate the postoperative outcomes of cataract eyes complicated with coexisting ocular pathologies that underwent implantation of a refractive multifocal intraocular lens (MIOL) with a surface-embedded near section. LENTIS MPlus (Oculentis GmbH) refractive MIOLs were implanted in 15 eyes with ocular pathologies other than cataract (ie, six high-myopia eyes with an axial length longer than 28 mm, two fundus albipunctatus eyes, two branch retinal-vein occlusion eyes, four glaucoma eyes (one with high myopia), and two keratoconus eyes). Uncorrected or corrected distance and near visual acuity (VA) (UDVA, UNVA, CDVA, and CNVA), contrast sensitivity, and defocus curve were measured at 1 day and 6 months postoperatively, and each patient completed a 6-month postoperative questionnaire regarding vision quality and eyeglass use. Thirteen eyes (87%) registered 0 or better in CDVA and 12 eyes (73%) registered better than 0 in CNVA. Contrast sensitivity in the eyes of all patients was comparable to that of normal healthy subjects. No patient required eyeglasses for distance vision, but three patients (20%) required them for near vision. No patient reported poor or very poor vision quality. With careful case selection, sectorial refractive MIOL implantation is effective for treating cataract eyes complicated with ocular pathologies.

Ozone depletion and solar ultraviolet radiation: ocular effects, a United nations environment programme perspective.

PubMed

Cullen, Anthony P

2011-07-01

To describe he role played by the United Nations Environmental Effects Panel with respect to the ocular effects of stratospheric ozone depletion and present the essence of the Health Chapter of the 2010 Assessment. A consideration of solar ultraviolet radiation (UVR) at the Earth's surface as it is affected by atmospheric changes and how these influence sunlight-related eye diseases. A review of the current Assessment with emphasis on pterygium, cataract, ocular melanoma, and age-related macular degeneration. Although the ozone layer is projected to recover slowly in the coming decades, continuing vigilance is required regarding exposure to the sun. Evidence implicating solar UVR, especially UVB, in every tissue of the eye continues to be amassed. The need for ocular UV protection existed before the discovery of the depletion of the ozone layer and will continue even when the layer fully recovers in approximately 2100.

Glycobiology of ocular angiogenesis

PubMed Central

Markowska, Anna I; Cao, Zhiyi; Panjwani, Noorjahan

2014-01-01

Ocular neovascularization can affect almost all the tissues of the eye: the cornea, the iris, the retina, and the choroid. Pathological neovascularization is the underlying cause of vision loss in common ocular conditions such as diabetic retinopathy, retinopathy of prematurity and age-related macular neovascularization. Glycosylation is the most common covalent posttranslational modification of proteins in mammalian cells. A growing body of evidence demonstrates that glycosylation influences the process of angiogenesis and impacts activation, proliferation, and migration of endothelial cells as well as the interaction of angiogenic endothelial cells with other cell types necessary to form blood vessels. Recent studies have provided evidence that members of the galectin class of β-galactoside-binding proteins modulate angiogenesis by novel carbohydrate-based recognition systems involving interactions between glycans of angiogenic cell surface receptors and galectins. This review discusses the significance of glycosylation and the role of galectins in the pathogenesis of ocular neovascularization. PMID:25108228

Profile of ocular trauma in industries-related hospital.

PubMed

Shashikala, P; Sadiqulla, Mohammed; Shivakumar, D; Prakash, K H

2013-05-01

Ocular trauma is a worldwide cause of visual morbidity, a significant proportion of which occurs in the industrial workplace and includes a spectrum of simple ocular surface foreign bodies, abrasions to devastating perforating injuries causing blindness. Being preventable is of social and medical concern. A prospective case series study, to know the profile of ocular trauma at a hospital caters exclusively to factory employees and their families, to co-relate their demographic and clinical profile and to identify the risk factors. Patients with ocular trauma who presented at ESIC Model hospital, Rajajinagar, Bangalore, from June 2010 to May 2011 were taken a detailed demographic data, nature and cause of injury, time interval between the time of injury and presentation along with any treatment received. Ocular evaluation including visual acuity, anterior and posterior segment findings, intra-ocular pressure and gonio-scopy in closed globe injuries, X-rays for intraocular foreign body, B-scan and CT scan were done. Data analyzed as per the ocular trauma classification group. The rehabilitation undertaken medically or surgically was analyzed. At follow-up, the final best corrected visual acuity was noted. A total of 306 cases of ocular trauma were reported; predominantly in 20-40 year age group (72.2%) and in men (75%). The work place related cases were 50.7%and of these, fall of foreign bodies led the list. Visual prognosis was poorer in road traffic accidents rather than work place injuries owing to higher occurrence of open globe injuries and optic neuropathy. Finally, 11% of injured cases ended up with poor vision. Targeting groups most at risk, providing effective eye protection, and developing workplace safety cultures may together reduce occupational eye injuries.

Colored corn starch dust explosion-related ocular injuries at a Taiwan water park: A preliminary report from a single medical center

PubMed Central

Liao, Yi-Lin; Yeh, Lung-Kun; Tsai, Yueh-Ju; Chen, Shin-Yi

2016-01-01

Purpose: To elucidate the manifestations of ocular injuries in the colored corn starch dust explosion at a Taiwan water park. Methods: This is a retrospective, non-comparative, consecutive-interventional case series. Fifty explosion-injury patients on 27 June 2015 treated at Chang-Gung Memorial Hospital, Linkou, were included. Thorough ophthalmic examinations were based on emergent triage and consecutive ophthalmological consultations. Multiple ocular and systemic parameters were assessed. Results: Of the 100 eyes in the 50 cases reviewed, 22 cases were male and 28 cases were female. The mean age was 22.08 ± 4.64 years, and the mean burn total body surface area (TBSA) of patients was 45.92 ± 20.30%. Of the 50 patients, 20 had Grade 1 ocular burns, and the others were without ocular involvement. Two of the 20 cases that presented Grade 1 ocular burns died within 1 month due to other systemic complications. The most common ocular manifestations among those with ocular injuries included periocular swelling (75%), followed by conjunctival chemosis (65%), conjunctival hyperemia (50%), singed eyelashes (20%), cornea epithelial defects (10%), and punctate keratopathy (5%). It is worth mentioning that one patient developed herpes simplex keratitis due to stress 3 weeks after being burned. Half of the 50 patients had facial burns. Specifically, the patients with a greater TBSA presented more significant ocular-burn manifestations than those patients with lower TBSA. Conclusion: Prompt ophthalmologic consultations are particularly necessary for mass burn-casualty patients with facial burns, inhalation injuries, and greater TBSA. The inspection and control of all ignition sources and the manipulation of dust with low concentrations and in an open space are crucial factors to prevent future dust explosions. PMID:29018726

The Effect of Ambient Titanium Dioxide Microparticle Exposure to the Ocular Surface on the Expression of Inflammatory Cytokines in the Eye and Cervical Lymph Nodes.

PubMed

Eom, Youngsub; Song, Jong Suk; Lee, Hyun Kyu; Kang, Boram; Kim, Hyeon Chang; Lee, Hyung Keun; Kim, Hyo Myung

2016-12-01

To investigate the ocular immune response following exposure to airborne titanium dioxide (TiO2) microparticles. Rats in the TiO2-exposed group (n = 10) were exposed to TiO2 particles for 2 hours twice daily for 5 days, while the controls (n = 10) were not. Corneal staining score and tear lactic dehydrogenase (LDH) activity were measured to evaluate ocular surface damage, serum immunoglobulin (Ig) G and E were assayed by using enzyme-linked immunosorbent assay, and the size of cervical lymph nodes was measured. In addition, the expression of interleukin (IL)-4, IL-17, and interferon (IFN)-γ in the anterior segment of the eyeball and cervical lymph nodes was measured by immunohistochemistry, real-time reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analysis. Median corneal staining score (3.0), tear LDH activity (0.24 optical density [OD]), and cervical lymph node size (36.9 mm2) were significantly higher in the TiO2-exposed group than in the control group (1.0, 0.13 OD, and 26.7 mm2, respectively). Serum IgG and IgE levels were found to be significantly elevated in the TiO2-exposed group (P = 0.021 and P = 0.021, respectively). Interleukin 4 expression was increased in the anterior segment of the eyeball and lymph nodes following TiO2 exposure, as measured by immunostaining, real-time RT-PCR, and Western blot. In addition, IL-17 and IFN-γ levels were also increased following TiO2 exposure compared to controls as measured by immunostaining. Exposure to airborne TiO2 induced ocular surface damage. The Type 2 helper T-cell pathway seems to play a dominant role in the ocular immune response following airborne TiO2 exposure.

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

A nonrandomized, open-label study to evaluate the effect of nasal stimulation on tear production in subjects with dry eye disease.

PubMed

Friedman, Neil J; Butron, Karla; Robledo, Nora; Loudin, James; Baba, Stephanie N; Chayet, Arturo

2016-01-01

Dry eye disease (DED), a chronic disorder affecting the tear film and lacrimal functional unit, is a widely prevalent condition associated with significant burden and unmet treatment needs. Since specific neural circuits play an important role in maintaining ocular surface health, microelectrical stimulation of these pathways could present a promising new approach to treating DED. This study evaluated the efficacy and safety of nasal electrical stimulation in patients with DED. This prospective, open-label, single-arm, nonrandomized pilot study included 40 patients with mild to severe DED. After undergoing two screening visits, enrolled subjects were provided with a nasal stimulation device and instructed to use it at home four times daily (or more often as needed). Follow-up assessments were conducted up to day 180. The primary efficacy endpoint was the difference between unstimulated and stimulated tear production quantified by Schirmer scores. Additional efficacy endpoints included change from baseline in corneal and conjunctival staining, symptoms evaluated on a Visual Analog Scale, and Ocular Surface Disease Index scores. Safety parameters included adverse event (AE) rates, visual acuity, intraocular pressure, slit-lamp biomicroscopy, indirect ophthalmoscopy, and endoscopic nasal examinations. Mean stimulated Schirmer scores were significantly higher than the unstimulated scores at all visits, and corneal and conjunctival staining and symptom scores from baseline to day 180 were significantly reduced. No serious device-related AEs and nine nonserious AEs (three device-related) were reported. Intraocular pressure remained stable and most subjects showed little or no change in visual acuity at days 30 and 180. No significant findings from other clinical examinations were noted. Neurostimulation of the nasolacrimal pathway is a safe and effective means of increasing tear production and reducing symptoms of dry eye in patients with DED.

Conjunctival impression cytology evaluation of patients with dry eye disease using scleral contact lenses.

PubMed

Weber, Sarah La Porta; Hazarbassanov, Rossen Mihaylov; Nasaré, Alex; Gomes, José Álvaro Pereira; Hofling-Lima, Ana Luisa

2017-06-01

To evaluate conjunctival impression cytology and HLADR expression changes after wearing scleral contact lenses (ScCLs) for moderate to severe dry eye disease (DED). Prospective interventional case series. Forty-one eyes from 25 patients with moderate to severe DED were evaluated for Esclera ScCL treatment. Best-corrected visual acuity (BCVA) and slit-lamp findings were assessed. Impression cytology specimens were obtained from DED patients at the baseline and after wearing ScCLs for 12 months. The impression cytology specimens were analyzed using morphological results score, and HLA-DR positive cells were detected and quantified. The values were compared to assess the IC changes after wearing ScCLs. Forty-one eyes from 25 patients were fitted with ScCLs to manage DED. The underlying diseases were Stevens-Johnson syndrome (22 eyes), Sjogren's syndrome (11 eyes), graft-versus-host disease (2 eyes), dry eye after keratomileusis (2 eyes) and undifferentiated ocular surface disease (4 eyes). The HE-PAS impression cytology score did not differ significantly before and after wearing ScCLs for 12 months in DED patients (p>0.05). The percentage of eyes expressing the HLA-DR antigen in the temporal conjunctiva after wearing ScCL for 12 months significantly increased in patients with Sjogren's syndrome (11.11% to 66.66%; p=0.0498). In groups with Stevens Johnson syndrome and other ocular surface disorders, we did not observe statistically significant differences (p>0.05). The ScCLs did not change the parameters used to evaluate inflammatory processes, which were measured using conjunctival impression cytology and HLA-DR expression, except in Sjogren syndrome, in which there was an unexpected increase in HLA expression. Copyright © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

Clinical study to assess the efficacy of Keshanjana and Netra Parisheka in the management of Shushkakshipaka (dry eye syndrome).

PubMed

Vardhan, Prabhakar; Dhiman, Kartar Singh

2014-01-01

Dry eye syndrome (DES) is a common ophthalmic problem predominantly affecting middle-aged and elderly people. It is a disease of deficient or deranged tears and ocular surface disorder producing symptoms of discomfort, visual disturbance, and tears film instability. Shushkakshipaka, an etymologically and clinically similar entity to DES, is defined in Ayurveda as the disease affecting all parts of the eye characterized by Paka (inflammation) due to Shuskatva (dryness) caused by altered coherence of Ashru (tears) with ocular surface or due to lack of Ashru. To compare the effect of Keshanjana and Netra Parisheka in Shushkakshipaka with artificial tear drops (carboxy methyl cellulose [CMC]). To search a safe, potent and cost-effective Ayurvedic treatment for DES, a randomized comparative clinical trial was conducted on 32 patients. Patients were divided in two groups 15 in group I and 17 in group II. Group I treated with artificial tear drop four times a day for topical use and group II treated with combination therapy of Keshanjana applied topically once a day and Netra Prisheka was done thrice a day. The effect of Ayurvedic management was found to be equivalent to the standard therapy, although the trial drugs provided more relief in foreign body sensation, burning sensation, dryness, pain, photophobia, itching, crusting, stuck eyelids, tear meniscus, conjunctival congestion, Schirmer I test, and tear film break-up time (TUBT). The standard therapy provided more relief than trial drugs in mucous discharges, transiently blurred vision, redness, and the presence of mucin debris in tear film. Keshanjana and Netra Parisheka can be used as a potent, safe and cost-effective treatment to ameliorate the symptoms of DES.

Clinical study to assess the efficacy of Keshanjana and Netra Parisheka in the management of Shushkakshipaka (dry eye syndrome)

PubMed Central

Vardhan, Prabhakar; Dhiman, Kartar Singh

2014-01-01

Background: Dry eye syndrome (DES) is a common ophthalmic problem predominantly affecting middle-aged and elderly people. It is a disease of deficient or deranged tears and ocular surface disorder producing symptoms of discomfort, visual disturbance, and tears film instability. Shushkakshipaka, an etymologically and clinically similar entity to DES, is defined in Ayurveda as the disease affecting all parts of the eye characterized by Paka (inflammation) due to Shuskatva (dryness) caused by altered coherence of Ashru (tears) with ocular surface or due to lack of Ashru. Aim: To compare the effect of Keshanjana and Netra Parisheka in Shushkakshipaka with artificial tear drops (carboxy methyl cellulose [CMC]). Materials and Methods: To search a safe, potent and cost-effective Ayurvedic treatment for DES, a randomized comparative clinical trial was conducted on 32 patients. Patients were divided in two groups 15 in group I and 17 in group II. Group I treated with artificial tear drop four times a day for topical use and group II treated with combination therapy of Keshanjana applied topically once a day and Netra Prisheka was done thrice a day. Results: The effect of Ayurvedic management was found to be equivalent to the standard therapy, although the trial drugs provided more relief in foreign body sensation, burning sensation, dryness, pain, photophobia, itching, crusting, stuck eyelids, tear meniscus, conjunctival congestion, Schirmer I test, and tear film break-up time (TUBT). The standard therapy provided more relief than trial drugs in mucous discharges, transiently blurred vision, redness, and the presence of mucin debris in tear film. Conclusion: Keshanjana and Netra Parisheka can be used as a potent, safe and cost-effective treatment to ameliorate the symptoms of DES. PMID:26664237

Goblet Cells of the Conjunctiva: A Review of Recent Findings

PubMed Central

Gipson, Ilene K

2016-01-01

Goblet cells within the conjunctival epithelium are specialized cells that secrete mucins onto the surface of the eye. Recent research has demonstrated new characteristics of the cells, including factors influencing their differentiation, their gene products and their functions at the ocular surface. The following review summarizes the newly discovered aspects of the role of Spdef, a member of the Ets transcription factor family in conjunctival goblet cell differentiation, the newly discovered goblet cell products including claudin2, the Wnt inhibitor Frzb, and the transmembrane mucin Muc16. The current concepts of conjunctival goblet cell function, including debris removal and immune surveillance are reviewed, as are changes in the goblet cell population in ocular surface diseases. Major remaining questions regarding conjunctival cell biology are discussed. PMID:27091323

Stability and Ocular Pharmacokinetics of Celecoxib-Loaded Nanoparticles Topical Ophthalmic Formulations.

PubMed

Ibrahim, Mohammed Mostafa; Abd-Elgawad, Abd-Elgawad Helmy; Soliman, Osama Abd-Elazeem; Jablonski, Monica M

2016-12-01

A spontaneous emulsification and/or solvent diffusion method was used for the preparation of celecoxib-loaded nanoparticles (NPs) using polymers, including chitosan (CS), sodium alginate, poly-ε-caprolactone (PCL), poly-l-lactide, and poly-d,l-lactide-co-glycolide. NPs were incorporated into vehicles (eye drops, in situ gelling system, and gel). Formulations were subjected to an accelerated stability study by storing them at elevated temperatures of 30, 35, and 45°C for 6 months. Formulations were evaluated monthly for general appearance, pH, viscosity, particle size, polydispersity index, zeta potential, and drug content. Gels containing CS-NPs and PCL-NPs were selected for an ocular pharmacokinetics study using Sprague-Dawley rats due to their high stability and long shelf lives (24.56 and 33.76 months, respectively). The gel improved NP stability by keeping it inside its network structure, which protected them from aggregation and interacting with water. Our formulations improved celecoxib bioavailability due to their bioadhesivness, thus preventing their rapid removal. Also, NPs acted as drug reservoirs that adhered to eye surface and continuously released the drug. The availability of celecoxib in all eye tissues and its absence in plasma suggests that our formulation could be used for anterior eye disorders and also for treatment of diseases associated with the posterior eye with no systemic side effects. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

A review of scoring systems for ocular involvement in chronic cutaneous bullous diseases.

PubMed

Lee, Brendon W H; Tan, Jeremy C K; Radjenovic, Melissa; Coroneo, Minas T; Murrell, Dedee F

2018-05-22

Epidermolysis bullosa (EB) and autoimmune blistering diseases (AIBD) describe a group of rare chronic dermatoses characterized by cutaneous fragility and blistering. Although uncommon, significant ocular surface disease (OSD) may occur in both and require ophthalmological assessment. Disease scoring systems have a critical role in providing objective and accurate assessment of disease severity. The objectives of this report were, firstly, to document the prevalence and severity of ocular involvement in EB/AIBD. Secondly, to review and evaluate existing ocular and systemic scoring systems for EB/AIBD. Finally, to identify areas where further development of ocular specific tools in EB/AIBD could be pursued. A literature search was performed in October 2017 utilising Medline, Embase, and Scopus databases. The results were restricted by date of publication, between 01.01.1950 and 31.10.2017. The reference lists of these articles were then reviewed for additional relevant publications. Articles of all languages were included if an English translation was available. Articles were excluded if they were duplicates, had no reference to ocular involvement in EB/AIBD or described ocular involvement in other diseases. Descriptions of ocular involvement in EB/AIBD were identified in 88 peer-reviewed journal articles. Findings reported include but are not limited to: cicatrising conjunctivitis, meibomian gland dysfunction, dry eye disease, trichiasis, symblepharon, fornix fibrosis, keratopathy, ectropion/entropion, ankyloblepharon, corneal ulceration, visual impairment and blindness. Although scoring systems exist for assessment of OSD in mucous membrane pemphigoid, no such tools exist for the other AIBD subtypes or for EB. Several systemic scoring systems exist in the dermatological literature that are efficacious in grading overall EB/AIBD severity, but have limited inclusion of ocular features. To the best of our knowledge, there is no recognised or validated scoring systems which comprehensively stages or grades the spectrum of ocular manifestations in EB/AIBD. There are a range of ocular complications documented in EB and AIBD. Development of a comprehensive ocular scoring system for EB/AIBD which incorporates the delineation between 'activity' and 'damage' would facilitate more objective patient assessment, improved longitudinal monitoring, comparison of intervention outcomes, and provide commonality for discussion of these patients due to the multidisciplinary nature of their care.

Frequency and risk factors associated with dry eye in patients attending a tertiary care ophthalmology center in Mexico City.

PubMed

Martinez, Jaime D; Galor, Anat; Ramos-Betancourt, Nallely; Lisker-Cervantes, Andrés; Beltrán, Francisco; Ozorno-Zárate, Jorge; Sánchez-Huerta, Valeria; Torres-Vera, Marco-Antonio; Hernández-Quintela, Everardo

2016-01-01

The purpose of this study was to ascertain the frequency and risk factors of dry eye (DE) among patients attending a tertiary care ophthalmology center in Mexico. Approximately 338 consecutive new patients attending a tertiary care ophthalmology center in Mexico City underwent an ocular surface examination, which included tear film break-up time, fluorescein corneal staining, Schirmer's test, and evaluation of meibum quality. Symptoms of DE were evaluated by the Ocular Surface Disease Index and Dry Eye Questionnaire-5. Information on demographics, exposures, past medical and ocular history, and medications was also collected. The frequency of severe DE symptoms was found to be 43% based on the Ocular Surface Disease Index and 30% based on Dry Eye Questionnaire-5. Risk factors significantly associated with increased DE symptoms included dry mouth and gastrointestinal ulcer medications. With regard to signs, aqueous tear deficiency was a less-frequent finding (22%) in our population than evaporative deficiency (94%). Risk factors associated with aqueous tear deficiency were dry mouth and diuretic use. No risk factors were associated with evaporative deficiency. Risk factors associated with meibomian gland dysfunction included old age, male sex, arthritis, and use of an antihypertensive. The only risk factor associated with corneal staining was dry mouth. This is the first study to demonstrate the frequency of symptomatic and clinical DE in a tertiary care ophthalmology center in Mexico. The frequency of DE ranged from 30% using a symptomatic definition to 94% using objective measures. Different risk factors were found for different aspects of DE, suggesting differing underlying pathophysiologies behind different DE subtypes.

A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

PubMed Central

Yang, Qian; Zhang, Yafang; Liu, Xiuping; Wang, Nan; Song, Zhenyu; Wu, Kaili

2017-01-01

Models of benzalkonium chloride (BAC)-induced ocular disruption have been created and are widely used in various animals. This study aimed to compare the effects of BAC on the ocular surfaces of C57BL/6 and BALB/c mice. C57BL/6 and BALB/c mice were treated separately with BAC eye-drops at different concentrations. Eyes were evaluated by scoring epithelial disruption, corneal opacity and neovascularization in vivo, and by histological assays with hematoxylin/eosin (H/E) and periodic acid-Schiff stainings and by determining the expression of inflammatory factors in vitro on Days 7 and 14. The in vivo corneal epithelial disruption, corneal edema/opacity and neovascularization, which were in accordance with the results of the H/E staining and peaked at Day 7, were observed in a dose-dependent manner in the BAC-treated mice, with more severe signs in the C57BL/6 mice than the BALB/c mice. The loss of conjunctival goblet cells in the conjunctivas and the increasing expression of monocyte chemoattractant protein 1 (MCP-1), growth-regulated protein alpha (GROa) and macrophage inflammatory protein-1 alpha (MIP-1a) in the corneas were found in a dose-dependent manner in both strains of mice. Topical application of BAC can dramatically disrupt the ocular surfaces of C57BL/6 and BALB/c mice, and the disruptions were much more severe in the C57BL/6 mice that received high doses of BAC. PMID:28245636

Glycerogelatin-based ocular inserts of aceclofenac: physicochemical, drug release studies and efficacy against prostaglandin E₂-induced ocular inflammation.

PubMed

Mathurm, Manish; Gilhotra, Ritu Mehra

2011-01-01

An attempt has been made in the present study to formulate soluble ocular inserts of aceclofenac to facilitate the bioavailability of the drug into the eye, as no eye drop solution could be formulated. Glycero-gelatin ocular inserts/films were prepared and physicochemical parameters and drug release profiles of glycerol-gelatin films of aceclofenac were compared with surface cross-linked films of similar compositions. Ocular irritation of the developed formulation was also checked by HET-CAM test and efficacy of the developed formulation against prostaglandin-induced ocular inflammation in rabbit eye was determined. The non-cross-linked films showed poor mechanical, physicochemical properties, and very little potential of sustaining drug release, however cross-linking the films enhanced tensile strength by 70%, but elasticity decreased by 95%. The cross-linked ocular inserts showed less swelling than non-cross-linked. Formulation AF8 (20% gelatin and 70% glycerin, treated by cross-linker for 1 h) demonstrated the longest drug release for 24 h. As per the kinetic models all films showed a constant drug release with Higuchi diffusion mechanism. Formulation was found to be practically non-irritant. The optimized formulation was tested and compared with eye drops of aceclofenac for anti-inflammatory activity in rabbits against PGE₂-induced inflammation. In vivo studies with developed formulation indicated a significant inhibition of PGE₂-induced PMN migration as compared to eye drops. In conclusion, ocular inserts of aceclofenac was found promising as it achieved sustained drug release and better pharmacodynamic activity.

The natural history of Stevens–Johnson syndrome: patterns of chronic ocular disease and the role of systemic immunosuppressive therapy

PubMed Central

De Rojas, M Victoria; Dart, John K G; Saw, Valerie P J

2007-01-01

Objective To characterize patterns of chronic ocular disease in patients with Stevens–Johnson syndrome (SJS) and its variant toxic epidermal necrolysis (TEN), and to describe their response to treatment. Methods Retrospective case series. A review of hospital records of 30 patients (60 eyes) with ocular manifestations of SJS or TEN was carried out. The principal outcome measure was to identify and classify the patterns of chronic ocular disease in SJS and TEN. The secondary outcome measure was the response to treatment. Results Patterns of chronic ocular disease observed after the acute episode included: mild/moderate SJS, severe SJS, ocular surface failure (SJS‐OSF), recurrent episodic inflammation (SJS‐RI), scleritis (SJS‐S) and progressive conjunctival cicatrisation resembling mucous membrane pemphigoid (SJS‐MMP). The median follow‐up was 5 years (range 0–29). 19 patients (29 eyes (48%)) developed SJS‐OSF, SJS‐RI, SJS‐S or SJS‐MMP during follow‐up. SJS‐OSF was present in 12 patients (18 eyes (30%)). In 5 patients (eight eyes) this developed 1 year after the acute illness, without any further inflammatory episodes; it was associated with SJS‐RI in 1 patient (2 eyes), with SJS‐RI and SJS‐S in 1 patient (1 eye), with SJS‐S in 1 patient (1 eye) and with SJS‐MMP in 4 patients (6 eyes). Episodes of SJS‐RI occurred in 4 patients (7 eyes (12%)). The median time from acute disease to the first episode of SJS‐RI was 8.5 years (range 5–63). SJS‐S developed in 2 patients (4 eyes (7%)), of which 2 eyes subsequently developed SJS‐OSF. SJS‐MMP developed in 5 patients (10 eyes (16.6%)). The median duration from the acute stage to the diagnosis of SJS‐MMP was 2 years (range 1–14). Immunosuppressive therapy successfully controlled inflammation in 10/10 patients with SJS‐MMP, SJS‐RI or SJS‐S. Conclusion Ocular disease in SJS/TEN is not limited solely to the sequelae of the acute phase illness. Patients and physicians need to know that ocular disease progression, due to surface failure and/or acute inflammatory conditions, may occur at variable periods following the acute disease episode. Recognition of this, and prompt access to specialist services, may optimise management of these uncommon patterns of disease in SJS. PMID:17314145

Long-term effect of surface light scattering and glistenings of intraocular lenses on visual function.

PubMed

Hayashi, Ken; Hirata, Akira; Yoshida, Motoaki; Yoshimura, Koichi; Hayashi, Hideyuki

2012-08-01

To investigate the long-term effect of surface light scattering and glistenings of various intraocular lenses (IOLs) on visual function and optical aberrations after cataract surgery. Case-control study. Thirty-five eyes that underwent implantation of a hydrophobic acrylic, silicone, or polymethyl methacrylate (PMMA) IOL more than 10 years ago were recruited. The scattering light intensity of the surface and internal matrix of the optic was measured using Scheimpflug photography. Visual acuity (VA) was measured using VA charts, and contrast VA and that with glare (glare VA) were examined using a contrast sensitivity tester. Ocular higher-order aberrations (HOAs) were measured using a Hartmann-Shack aberrometer. Mean scattering light intensity of the surface and internal matrix of the optic was significantly higher in the acrylic group than in the silicone and PMMA groups (P < .0001). Mean uncorrected VA, photopic and mesopic contrast VA and glare VA, and HOAs did not differ significantly among groups, although mean corrected VA in the acrylic group was significantly better than that in the other groups (P = .0023). Scattering light intensity of the surface and internal matrix did not correlate with VA, contrast VA, or glare VA, and did not correlate with ocular and internal optic HOAs in the acrylic group. At more than 10 years postoperatively, visual function, including contrast sensitivity, and ocular HOAs were comparable among eyes that received acrylic, silicone, and PMMA IOLs. Surface scattering and glistenings with the acrylic IOLs were not significantly correlated with visual function and optical aberrations. Copyright © 2012 Elsevier Inc. All rights reserved.

Nanostructured lipid carriers as novel ophthalmic delivery system for mangiferin: improving in vivo ocular bioavailability.

PubMed

Liu, Rui; Liu, Zhidong; Zhang, Chengui; Zhang, Boli

2012-10-01

The aim of this study was to develop a novel nanostructured lipid carriers (NLCs) system to improve ocular bioavailability of mangiferin (MGN) for the potential treatment of cataract. The physicochemical properties of MGN-loaded NLC (MGN-NLC) formulation were characterized by particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, morphological property, and crystalline state. in vitro characteristics were investigated by drug release from NLC system, physical stability, and corneal permeation through excised rabbit cornea. Moreover, in vivo ocular tolerability was assessed by a modified Draize test and histological microscopy. Preocular retention capability was evaluated by slit-lamp observation. Pharmacokinetic study in the aqueous humor was performed by microdialysis technique. Transmission electron microscopy depicted spherical and uniform morphology. Differential scanning calorimetry and X-ray diffractometry displayed imperfect crystalline lattice. The optimized MGN-NLC formulation exhibited a sustained drug release with 3 months stability and 4.31-fold increase of in vitro corneal permeation. Furthermore, in vivo studies exhibited a high tolerance in the ocular tissues and prolonged drug retention capacity on the corneal surface. Finally, pharmacokinetic study suggested a 5.69-fold increase of ocular bioavailability compared with MGN solution (MGN-SOL). Therefore, NLC system is a promising approach for ocular delivery of MGN. Copyright © 2012 Wiley Periodicals, Inc.

Microscopic and spectroscopic evaluation of novel PLGA-chitosan Nanoplexes as an ocular delivery system.

PubMed

Jain, Gaurav K; Pathan, Shadab A; Akhter, Sohail; Jayabalan, Nirmal; Talegaonkar, Sushma; Khar, Roop K; Ahmad, Farhan J

2011-02-01

The interaction of PLGA-chitosan Nanoplexes with ocular mucosa was investigated ex vivo and in vivo to assess their potential as ocular delivery system. Fluorescent Rhodamine Nanoplexes (Rd-Nanoplexes) were prepared by ionotropic gelation method. The size and morphology of Nanoplexes was investigated by TEM, SEM and PCS. The corneal retention, uptake and penetration of Nanoplexes were analyzed by spectrofluorimetry and confocal microscopy. Corneas from Rd-Nanoplexes-treated rabbits were evaluated for the in vivo uptake and ocular tolerance. The Nanoplexes prepared were round with a mean diameter of 115.6±17nm and the encapsulation efficiency of Rd was 59.4±2.5%. Data from ex vivo and in vivo studies showed that the amounts of Rd in the cornea were significantly higher for Nanoplexes than for a control Rd solution, these amounts being fairly constant for up to 24h. Confocal microscopy of the corneas revealed paracellular and transcellular uptake of the Nanoplexes. The uptake mechanism postulated was adsorptive-mediated endocytosis and opening of the tight junctions between epithelial cells. No alteration was microscopically observed after ocular surface exposure to Nanoplexes. Taken together, these data demonstrate that Nanoplexes are potentially useful as ocular drug carriers. Copyright © 2010 Elsevier B.V. All rights reserved.

Analysis of nystagmus response to a pseudorandom velocity input

NASA Technical Reports Server (NTRS)

Lessard, C. S.

1986-01-01

Space motion sickness was not reported during the first Apollo missions; however, since Apollo 8 through the current Shuttle and Skylab missions, approximately 50% of the crewmembers have experienced instances of space motion sickness. Space motion sickness, renamed space adaptation syndrome, occurs primarily during the initial period of a mission until habilation takes place. One of NASA's efforts to resolve the space adaptation syndrome is to model the individual's vestibular response for basis knowledge and as a possible predictor of an individual's susceptibility to the disorder. This report describes a method to analyse the vestibular system when subjected to a pseudorandom angular velocity input. A sum of sinusoids (pseudorandom) input lends itself to analysis by linear frequency methods. Resultant horizontal ocular movements were digitized, filtered and transformed into the frequency domain. Programs were developed and evaluated to obtain the (1) auto spectra of input stimulus and resultant ocular resonse, (2) cross spectra, (3) the estimated vestibular-ocular system transfer function gain and phase, and (4) coherence function between stimulus and response functions.

OCT-based profiler for automating ocular surface prosthetic fitting (Conference Presentation)

NASA Astrophysics Data System (ADS)

Mujat, Mircea; Patel, Ankit H.; Maguluri, Gopi N.; Iftimia, Nicusor V.; Patel, Chirag; Agranat, Josh; Tomashevskaya, Olga; Bonte, Eugene; Ferguson, R. Daniel

2016-03-01

The use of a Prosthetic Replacement of the Ocular Surface Environment (PROSE) device is a revolutionary treatment for military patients that have lost their eyelids due to 3rd degree facial burns and for civilians who suffer from a host of corneal diseases. However, custom manual fitting is often a protracted painful, inexact process that requires multiple fitting sessions. Training for new practitioners is a long process. Automated methods to measure the complete corneal and scleral topology would provide a valuable tool for both clinicians and PROSE device manufacturers and would help streamline the fitting process. PSI has developed an ocular anterior-segment profiler based on Optical Coherence Tomography (OCT), which provides a 3D measure of the surface of the sclera and cornea. This device will provide topography data that will be used to expedite and improve the fabrication process for PROSE devices. OCT has been used to image portions of the cornea and sclera and to measure surface topology for smaller contact lenses [1-3]. However, current state-of-the-art anterior eye OCT systems can only scan about 16 mm of the eye's anterior surface, which is not sufficient for covering the sclera around the cornea. In addition, there is no systematic method for scanning and aligning/stitching the full scleral/corneal surface and commercial segmentation software is not optimized for the PROSE application. Although preliminary, our results demonstrate the capability of PSI's approach to generate accurate surface plots over relatively large areas of the eye, which is not currently possible with any other existing platform. Testing the technology on human volunteers is currently underway at Boston Foundation for Sight.

[Biopsychosocial profile of patients with anophthalmia in the south of Minas Gerais - Brazil].

PubMed

Cabral, Luiz Gustavo Megda; Martelli Júnior, Hercílio; Leite, Denise Moura; Sabatini Júnior, David; Freitas, Amanda Beatriz Dahdah Aniceto de; Miranda, Roseli Teixeira; Swerts, Mário Sérgio Oliveira; Barros, Letízia Monteiro de

2008-01-01

To evaluate the biopsychosocial profile of patients with anophthalmia, with emphasis on the psychological and functional impact of eye loss and the social reintegration of this population. Prospective analyses of 84 patients (50 males and 34 females), rehabilitated or in the rehabilitation process with ocular prostheses were interviewed by means of a questionnaire with dimensions involving the etiology of the ocular defect, degree of adaptation to the ocular prosthesis, and impact on professional, family and social activities. The right eye was affected in 45.2% of the patients, the left eye in 51.2%, and the rest of the patients had bilateral anophthalmia. Difficulty in adapting to monocular vision was reported by 47.6% of the patients. The main causes of anophthalmia in males were eye injuries due to accidents (54%), and, in females, acquired diseases (38.2%). For the total studied population, the eye loss occurred at a mean of 20.5 +/- 18.41 years, and the elapsed time until the first rehabilitation with ocular prosthesis was of 8.6 +/- 13.10 years. Most patients (66.1%) reported satisfaction and good adaptation to the prosthesis. Feelings of sadness, shame and shyness were frequently reported. Anophtalmic patients often exhibit psychic and/or functional disorders which hinder their social, professional and family readaptation, and this is aggravated by both economic factors and lack of public services that provide rehabilitative treatment. Public information campaigns could also be useful to prevent causes that lead to ocular loss.

HIV-1 gp120 Glycoprotein Interacting with Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Non-integrin (DC-SIGN) Down-Regulates Tight Junction Proteins to Disrupt the Blood Retinal Barrier and Increase Its Permeability.

PubMed

Qian, Yi-Wen; Li, Chuan; Jiang, Ai-Ping; Ge, Shengfang; Gu, Ping; Fan, Xianqun; Li, Tai-Sheng; Jin, Xia; Wang, Jian-Hua; Wang, Zhi-Liang

2016-10-28

Approximately 70% of HIV-1 infected patients acquire ocular opportunistic infections and manifest eye disorders during the course of their illness. The mechanisms by which pathogens invade the ocular site, however, are unclear. Under normal circumstances, vascular endothelium and retinal pigment epithelium (RPE), which possess a well developed tight junction complex, form the blood-retinal barrier (BRB) to prevent pathogen invasion. We hypothesize that disruption of the BRB allows pathogen entry into ocular sites. The hypothesis was tested using in vitro models. We discovered that human RPE cells could bind to either HIV-1 gp120 glycoproteins or HIV-1 viral particles. Furthermore, the binding was mediated by dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) expressed on RPE cells. Upon gp120 binding to DC-SIGN, cellular NF-κB signaling was triggered, leading to the induction of matrix metalloproteinases, which subsequently degraded tight junction proteins and disrupted the BRB integrity. DC-SIGN knockdown or prior blocking with a specific antibody abolished gp120-induced matrix metalloproteinase expression and reduced the degradation of tight junction proteins. This study elucidates a novel mechanism by which HIV, type 1 invades ocular tissues and provides additional insights into the translocation or invasion process of ocular complication-associated pathogens. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of Gabapentin/Memantine on the Infantile Nystagmus Syndrome in the Zebrafish Model: Implications for the Therapy of Ocular Motor Diseases.

PubMed

Bögli, Stefan Yu; Afthinos, Maresa; Huang, Melody Ying-Yu

2017-06-01

Infantile nystagmus syndrome (INS) is a disorder characterized by typical horizontal eye oscillations. Due to the uncertain etiology of INS, developing specific treatments remains difficult. Single reports demonstrated, on limited measures, alleviating effects of gabapentin and memantine. In the current study, we employed the zebrafish INS model belladonna (bel) to conduct an in-depth study of how gabapentin and memantine interventions alleviate INS signs, which may further restore visual conditions in affected subjects. Moreover, we described the influence of both medications on ocular motor functions in healthy zebrafish, evaluating possible iatrogenic effects. Ocular motor function and INS characteristics were assessed by eliciting optokinetic response, spontaneous nystagmus, and spontaneous saccades in light and in dark, in 5- to 6-day postfertilization bel larvae and heterozygous siblings. Single larvae were recorded before and after a 1-hour drug treatment (200 mM gabapentin/0.2 mM memantine). Both interventions significantly reduced nystagmus intensity (gabapentin: 59.98%, memantine: 39.59%). However, while the application of gabapentin affected all tested ocular motor functions, memantine specifically reduced nystagmus amplitude and intensity, and thus left controls completely unaffected. Finally, both drug treatments resulted in specific changes in nystagmus waveform and velocity. Our study provides deeper insight into gabapentin and memantine treatment effect in the zebrafish INS model. Moreover, this study should establish zebrafish as a pharmacologic animal model for treating nystagmus and ocular motor disease, serving as a basis for future large-scale drug screenings.

Unilateral glaucoma in Sotos syndrome (cerebral gigantism).

PubMed

Yen, M T; Gedde, S J; Flynn, J T

2000-12-01

To report a patient with unilateral glaucoma associated with Sotos syndrome. Sotos syndrome (cerebral gigantism) is a disorder of growth and development with characteristic facial changes and normal endocrine function. Ocular manifestations may also include megalocornea, iris hypoplasia, cataracts, megalophthalmos, strabismus, nystagmus, and retinal dystrophy. Case report. A 50 year-old man with the clinical features of Sotos syndrome presented with complaints of decreased vision in the left eye. Ophthalmologic examination revealed bilateral megalocornea, megalophthalmos, iris hypoplasia and transillumination defects, cataracts, and unilateral glaucoma. Intraocular pressure was lowered, and visual field loss was stabilized with topical medications. Sotos syndrome patients should be examined routinely to allow for early detection and treatment of potential ocular problems, including glaucoma.

Prevalence of dry eye syndrome after allogeneic hematopoietic stem cell transplantation.

PubMed

Ivanir, Yair; Shimoni, Avichai; Ezra-Nimni, Orit; Barequet, Irina S

2013-05-01

To evaluate the prevalence, severity, and effect of dry eye in patients after allogeneic hematopoietic stem cell transplantation (aHSCT) and to correlate the findings to the duration after transplantation. A total of 222 eyes of 111 patients after aHSCT at the Department of Bone Marrow Transplantation, Sheba Medical Center, Israel in a consecutive 3-year period. All patients underwent a full ophthalmic examination and filled the ocular surface disease index (OSDI) questionnaire to assess ocular involvement in the form of dry eye syndrome or any other ocular manifestation. The main outcome measures were best-corrected visual acuity, tear break-up time, corneal fluorescein staining, Schirmer test, and OSDI questionnaire. A total of 111 patients were recruited. In 37%, a diagnosis of ocular graft versus host disease was previously made and 46% had no previous ocular examination. Schirmer test was less than 5 mm in 50% of all patients, and in 30% of patients with undiagnosed ocular involvement. The mean OSDI score was 13, and in 28% it was above 20. Correlation was found between visual acuity decrease and high OSDI score to the diagnosis of ocular graft versus host disease and signs of dry eye syndrome. A trend of worsening dry eye was observed up to the second half of the second year posttransplantation. Although many patients are either asymptomatic or do not seek ophthalmic examination, severe dry eye is a common finding after aHSCT. Mandatory follow-up, patient education, and early treatment may improve the quality of life.

[Preservatives in ophthalmology].

PubMed

Messmer, E M

2012-11-01

Preservatives are a legal requirement for eye drops in multidose containers. Moreover, they are necessary for stabilization and intraocular penetration for a number of ophthalmic preparations. Most preservatives act in a relatively unspecific manner as detergents or by oxidative mechanisms and thereby cause side effects at the ocular surface. They may also affect the lens, trabecular meshwork and the retina. Benzalkonium chloride is the most commonly used preservative in ophthalmology and is more toxic than other or newer preservatives, such as polyquaternium-1 (Polyquad), sodium perborate, oxychloro-complex (Purite®) and SofZia. Preservative-free topical medication is highly recommended for patients with ocular surface disease, frequent eye drop administration, proven allergy to preservatives and contact lens wear.