Research in Dry Eye: Report of the Research Subcommittee of the International Dry Eye WorkShop (2007)

doi:10.1016/S1542-0124(12)70086-1

The Ocular Surface

Volume 5, Issue 2, April 2007, Pages 179-193

https://doi.org/10.1016/S1542-0124(12)70086-1 Get rights and content

Abstract

Members of the DEWS Research Subcommittee reviewed research into the basic mechanisms underlying dry eye disease. Evidence was evaluated concerning the tear film, lacrimal gland and accessory lacrimal glands, ocular surface epithelia (including cornea and conjunctiva), meibomian glands, lacrimal duct system and the immune system. Consideration was given to both animal and human research data. Results are presented as a series of information matrices, identifying what is known and providing supporting references. An attempt is made to identify areas for further investigation.

References (216)

WD Mathers et al.
Tear flow and evaporation in patients with and without dry eye
Ophthalmology
(1996)
CH Dohlman et al.
The glycoprotein (mucus) content of tears from normals and dry eye patients
Exp Eye Res
(1976)
Y Ohashi et al.
Abnormal protein profiles in tears with dry eye syndrome
Am J Ophthalmol
(2003)
M Tishler et al.
Elevated tear interleukin-6 levels in patients with Sjogren syndrome
Ophthalmology
(1998)
JP Gilbard et al.
Tear film and ocular surface changes after closure of the meibomian gland orifices in the rabbit
Ophthalmology
(1989)
SC Pflugfelder et al.
Correlation of goblet cell density and mucosal epithelial membrane mucin expression with rose bengal staining in patients with ocular irritation
Ophthalmology
(1997)
A Sommer
Treatment of corneal xerophthalmia with topical retinoic acid
Am J Ophthalmol
(1983)
J Horwath-Winter et al.
Early changes in corneal sensation, ocular surface integrity, and tear-film function after laserassisted subepithelial keratectomy
J. Cataract Refract Surg
(2004)
JA Hovanesian et al.
Symptoms of dry eye and recurrent erosion syndrome after refractive surgery
J Cataract Refract Surg
(2001)
SE Wilson
Laser in situ keratomileusis-induced (presumed) neurotrophic epitheliopathy
Ophthalmology
(2001)

IU Scott et al.

Endophthalmitis associated with microbial keratitis

Ophthalmology

(1996)

S Kawasaki et al.

Up-regulated gene expression in the conjunctival epithelium of patients with Sjogren's syndrome

Exp Eye Res

(2003)

JP Gilbard et al.

Tear film and ocular surface changes in a rabbit model of neurotrophic keratitis

Ophthalmology

(1990)

MA Lemp

Report of the National Eye Institute/Industry Workshop on clinical trials in dry eyes

CLAO J

(1995)

JP Gilbard et al.

Osmolarity of tear microvolumes in keratoconjunctivitis sicca

Arch Ophthalmol

(1978)

RL Farris et al.

Diagnostic tests in keratoconjunctivitis sicca

CLAO J

(1983)

JJ Nichols et al.

Tear film, contact lens, and patient-related factors associated with contact lens-related dry eye

Invest Ophthalmol Vis Sci

(2006)

KL Krenzer et al.

Effect of androgen deficiency on the human meibomian gland and ocular surface

J Clin Endocrinol Metab

(2000)

WD Mathers et al.

Meibomian gland dysfunction in chronic blepharitis

Cornea

(1991)

K Tsubota et al.

Tear evaporation from the ocular surface

Invest Ophthalmol Vis Sci

(1992)

E Goto et al.

Tear evaporation dynamics in normal subjects and subjects with obstructive meibomian gland dysfunction

Invest Ophthalmol Vis Sci

(2003)

JM Cermak et al.

Is complete androgen insensitivity syndrome associated with alterations in the meibomian gland and ocular surface?

Cornea

(2003)

JC Mainstone et al.

Tear meniscus measurement in the diagnosis of dry eye

Curr Eye Res

(1996)

GU Kallarackal et al.

A comparative study to assess the clinical use of fluorescein meniscus time (FMT) with tear break up time (TBUT) and Schirmer's tests (ST) in the diagnosis of dry eyes

Eye

(2002)

G Savini et al.

Tear meniscus evaluation by optical coherence tomography

Ophthalmic Surg Lasers Imaging

(2006)

JP Craig et al.

Importance of the lipid layer in human tear film stability and evaporation

Optom Vis Sci

(1997)

JP Craig et al.

The role of tear physiology in ocular surface temperature

Eye

(2000)

JM Tiffany et al.

Tear film stability and tear surface tension

Curr Eye Res

(1989)

B Nagyova et al.

Components responsible for the surface tension of human tears

Curr Eye Res

(1999)

MJ Glasson et al.

Differences in clinical parameters and tear film of tolerant and intolerant contact lens wearers

Invest Ophthalmol Vis Sci

(2003)

CG Begley et al.

The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity

Invest Ophthalmol Vis Sci

(2003)

M Yamada et al.

Decreased tear lipocalin concentration in patients with meibomian gland dysfunction

Br J Ophthalmol

(2005)

P Argueso et al.

Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren's syndrome

Invest Ophthalmol Vis Sci

(2002)

H Zhao et al.

Quantification of MUC5AC protein in human tears

Cornea

(2001)

E Goto et al.

Differentiation of lipid tear deficiency dry eye by kinetic analysis of tear interference images

Arch Ophthalmol

(2003)

Y Danjo et al.

Observation of precorneal tear film in patients with Sjogren's syndrome

Acta Ophthalmol Scand

(1995)

WE Shine et al.

Keratoconjunctivitis sicca associated with meibomian secretion polar lipid abnormality

Arch Ophthalmol

(1998)

FH Grus et al.

Analysis of tear protein patterns for the diagnosis of dry eye

Adv Exp Med Biol

(2002)

T Virtanen et al.

Tear fluid plasmin activity of dry eye patients with Sjogren's syndrome

Acta Ophthalmol Scand

(1997)

AA Afonso et al.

Tear fluid gelatinase B activity correlates with IL-1alpha concentration and fluorescein clearance in ocular rosacea

Invest Ophthalmol Vis Sci

(1999)

L Sobrin et al.

Regulation of MMP-9 activity in human tear fluid and corneal epithelial culture supernatant

Invest Ophthalmol Vis Sci

(2000)

FH Grus et al.

SELDI-TOF-MS ProteinChip array profiling of tears from patients with dry eye

Invest Ophthalmol Vis Sci

(2005)

Y Danjo et al.

Ocular surface damage and tear lactoferrin in dry eye syndrome

Acta Ophthalmol (Copenh)

(1994)

BS Koo et al.

Comparative analysis of the tear protein expression in blepharitis patients using two-dimensional electrophoresis

J Proteome Res

(2005)

DV Seal

The effect of aging and disease on tear constituents

Trans Ophthalmol Soc UK

(1985)

M Glasson et al.

Lipid, lipase and lipocalin differences between tolerant and intolerant contact lens wearers

Curr Eye Res

(2002)

VV Aho et al.

Group IIA phospholipase A2 content of tears in patients with keratoconjunctivitis sicca

Graefes. Arch Clin Exp Ophthalmol

(2002 Jul)

Pflugfelder SC, Jones D, Ji Z, et al. Altered cytokine balance in the tear fluid and conjunctiva of patients with...

A Solomon et al.

Pro- and anti-inflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with dry-eye disease

Invest Ophthalmol Vis Sci

(2001)

MP Molloy et al.

Establishment of the human reflex tear 2D-PAGE reference map: a first step towards the diagnosis of disease

Electrophoresis

(1997)

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Hyperosmolarity of the ocular surface triggers inflammation and pathological damage in dry eye disease (DED). In addition to a reduction in quality of life, DED causes vision loss and when severe, blindness. Mitochondrial dysfunction occurs as a consequence of hyperosmolar stress. We have previously reported on a role for the insulin-like growth factor binding protein-3 (IGFBP-3) in the regulation of mitochondrial ultrastructure and metabolism in mucosal surface epithelial cells; however, this appears to be context-specific. Due to the finding that IGFBP-3 expression is decreased in response to hyperosmolar stress in vitro and in an animal model of DED, we next sought to determine whether the hyperosmolar stress–mediated decrease in IGFBP-3 alters mitophagy, a key mitochondrial quality control mechanism. Here we show that hyperosmolar stress induces mitophagy through differential regulation of BNIP3L/NIX and PINK1-mediated pathways. In corneal epithelial cells, this was independent of p62. The addition of exogenous IGFBP-3 abrogated the increase in mitophagy. This occurred through regulation of mTOR, highlighting the existence of a new IGFBP-3–mTOR signaling pathway. Together, these findings support a novel role for IGFBP-3 in mediating mitochondrial quality control in DED and have broad implications for epithelial tissues subject to hyperosmolar stress and other mitochondrial diseases.
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Étude transversale incluant 155 patients glaucomateux. Tous ont répondu au questionnaire « Ocular Surface Disease Index » (OSDI) et ont eu un examen ophtalmologique complet avec une évaluation précise de l’état de la surface oculaire. L’évaluation comprenait un test Shirmer I, une évaluation du TBUT (tear beak up time), un examen des paupières, de la conjonctive et de la cornée avec un test à la fluorescéine et au vert de Lissamine. Nous avons analysé les facteurs pouvant influencer le score OSDI et sa relation avec les signes biomicroscopiques.
Le score OSDI était ≥ 13 dans 61,3 % des cas et sévère dans 22,6 % des cas. Les altérations biomicroscopiques de la surface oculaire étaient au moins minimes dans 87,1 % des cas. Le score OSDI était statistiquement liée à l’âge (p < 0,001), la durée du traitement (p < 0,001), la plurithérapie (p = 0,011), l’utilisation du BAK (p = 0,004) ainsi qu’à la blépharite (p = 0,013), le dysfonctionnement Meibomien (p = 0,039), les néovaisseaux cornéens (p = 0,025) et la kératite ponctuée superficielle (KPS) (p = 0,044). Une discordance entre les signes fonctionnels et biomicroscopiques a été notée.
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Research Subcommittee members: Ilene K. Gipson, PhD (Chair); Pablo Argüeso, PhD; Roger Beuerman, PhD; Stefano Bonini, MD; Igor Butovich, PhD; Reza Dana, MD, MPH; Darlene Dartt, PhD; Dan Gamache, PhD; Bryan Ham, PhD; Marcia Jumblatt, PhD; Donald Korb, OD; Friederich Kruse, MD; Yoko Ogawa, MD; Friedrich Paulsen, MD, PhD; Michael Stern, PhD; Deborah F. Sweeney, PhD; John Tiffany, PhD; John Ubels, PhD; Mark Willcox, PhD.

Proprietary interests of Subcommittee members are disclosed on pages 202 and 204.

Reprints are not available. Articles can be accessed at: www.tearfilm.org

Correspondence related to this chapter of the DEWS Report should be directed to: Ilene K. Gipson PhD, Schepens Eye Research Inst, 20 Staniford Street, Boston, MA 02114-2500. Tel: 617-912-0210. Fax: 617-912-0126. Email: [email protected]

Pablo Argüeso participated in the writing of the manuscript.

View full text

DEWS Clinical and Basic ResearchResearch in Dry Eye: Report of the Research Subcommittee of the International Dry Eye WorkShop (2007)

Abstract

Ophthalmology

Exp Eye Res

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Am J Ophthalmol

J. Cataract Refract Surg

J Cataract Refract Surg

Ophthalmology

Ophthalmology

Exp Eye Res

Ophthalmology

Report of the National Eye Institute/Industry Workshop on clinical trials in dry eyes

CLAO J

Osmolarity of tear microvolumes in keratoconjunctivitis sicca

Arch Ophthalmol

Diagnostic tests in keratoconjunctivitis sicca

CLAO J

Tear film, contact lens, and patient-related factors associated with contact lens-related dry eye

Invest Ophthalmol Vis Sci

Effect of androgen deficiency on the human meibomian gland and ocular surface

J Clin Endocrinol Metab

Meibomian gland dysfunction in chronic blepharitis

Cornea

Tear evaporation from the ocular surface

Invest Ophthalmol Vis Sci

Tear evaporation dynamics in normal subjects and subjects with obstructive meibomian gland dysfunction

Invest Ophthalmol Vis Sci

Is complete androgen insensitivity syndrome associated with alterations in the meibomian gland and ocular surface?

Cornea

Tear meniscus measurement in the diagnosis of dry eye

Curr Eye Res

A comparative study to assess the clinical use of fluorescein meniscus time (FMT) with tear break up time (TBUT) and Schirmer's tests (ST) in the diagnosis of dry eyes

Eye

Tear meniscus evaluation by optical coherence tomography

Ophthalmic Surg Lasers Imaging

Importance of the lipid layer in human tear film stability and evaporation

Optom Vis Sci

The role of tear physiology in ocular surface temperature

Eye

Tear film stability and tear surface tension

Curr Eye Res

Components responsible for the surface tension of human tears

Curr Eye Res

Differences in clinical parameters and tear film of tolerant and intolerant contact lens wearers

Invest Ophthalmol Vis Sci

The relationship between habitual patient-reported symptoms and clinical signs among patients with dry eye of varying severity

Invest Ophthalmol Vis Sci

Decreased tear lipocalin concentration in patients with meibomian gland dysfunction

Br J Ophthalmol

Decreased levels of the goblet cell mucin MUC5AC in tears of patients with Sjogren's syndrome

Invest Ophthalmol Vis Sci

Quantification of MUC5AC protein in human tears

Cornea

Differentiation of lipid tear deficiency dry eye by kinetic analysis of tear interference images

Arch Ophthalmol

Observation of precorneal tear film in patients with Sjogren's syndrome

Acta Ophthalmol Scand

Keratoconjunctivitis sicca associated with meibomian secretion polar lipid abnormality

Arch Ophthalmol

Analysis of tear protein patterns for the diagnosis of dry eye

Adv Exp Med Biol

Tear fluid plasmin activity of dry eye patients with Sjogren's syndrome

Acta Ophthalmol Scand

Tear fluid gelatinase B activity correlates with IL-1alpha concentration and fluorescein clearance in ocular rosacea

Invest Ophthalmol Vis Sci

Regulation of MMP-9 activity in human tear fluid and corneal epithelial culture supernatant

Invest Ophthalmol Vis Sci

SELDI-TOF-MS ProteinChip array profiling of tears from patients with dry eye

Invest Ophthalmol Vis Sci

Ocular surface damage and tear lactoferrin in dry eye syndrome

Acta Ophthalmol (Copenh)

Comparative analysis of the tear protein expression in blepharitis patients using two-dimensional electrophoresis

J Proteome Res

The effect of aging and disease on tear constituents

Trans Ophthalmol Soc UK

Lipid, lipase and lipocalin differences between tolerant and intolerant contact lens wearers

DEWS Clinical and Basic Research
Research in Dry Eye: Report of the Research Subcommittee of the International Dry Eye WorkShop (2007)