1. of Ocular Surface Disease
Dry Eye and
Molecular Mechanism
of Ocular Surface Disease
여의도성모병원
김 현 승

2. 외래 환자들 중 건성안 환자가 차지하는 비율은? 40% 이상 10% 미만 10.2% (20명) 9.2% (18명) 30~40%
외래 환자들 중 건성안 환자가 차지하는 비율은?
40% 이상
10.2% (20명)
10% 미만
9.2% (18명)
30~40%
15.8% (31명)
10~20%
27.0% (53명)
20~30%
37.8% (74명)
조사대상 ; 197명 안과 전문의
2006년 한국외안부연구회 건성안 심포지움

3. CONTENTS 01 Concepts and Definition 02 Classification 03
Treatment Guideline 04
Molecular Mechanism 05
Related Experiment

5. Instability of Tear film
Definition of Dry Eye
National Eye Institute (1994)
Tear Deficiency or Excessive Evaporation
Instability of Tear film
Damage to the Ocular surface
Symptoms of Ocular discomfort

6. Lacrimal Gland Functional Unit
Ocular Surface and
Lacrimal Gland Functional Unit
Emotion 
Neurogenic Inflammation
Immune Activation
Role of Androgens
Maintain Anti-inflammatory
State of the Functional Unit
Normalization of Meibomian
Lipid Composition
Restoration of Ocular Surface
CNS
CN VII Efferent Parasympathetic    
CN V1 Afferent 
“Tears on Demand”
Tear Support & Maintain Ocular Surface
Pflugfelder at al. 1998, Cornea

7. Pathology in Dry Eye Patients
Langerhans cells in conjunctiva
Abnormal expression of class II HLA DR Ag
Abnormal expression ICAM-1 protein
Abnormal increase of dendritic cells
Baudouin C. The Pathology of Dry Eye. Surv Ophthalmol 45(Suppl 2);2001:S211–20.
Gao J, Morgan G, Tieu D, Schwalb TA, Luo JY, Wheeler LA, Stern ME. ICAM-1 expression predisposes ocular tissues to immune-based inflammation in dry eye patients and Sjögrens syndrome-like MRL/lpr mice. Exper Eye Res 2004;78:823–835.

8. Interrupted Secretomotor Tears Inflame Ocular Surface
Dry Eye Disease; “An Immune-Mediated Inflammatory Disorder”
Interrupted Secretomotor
Nerve Impulses
Lacrimal Glands:
Neurogenic inflammation
T- cell activation
Cytokine secretion into tears
Tears Inflame Ocular Surface
Cytokines
Disrupt Neural Arc
Pflugfelder SC, Cornea, 2000

9. - 17 international specialists on dry eye in Delphi Panel
Dysfunctional Tear Syndrome
A Delphi Approach to Treatment Recommendations
- 17 international specialists on dry eye in Delphi Panel
Pupose ▶
current classification of aqueous-deficient versus evaporative
dry eye failed to incorporate inflammatory mechanisms
Proposes a new terminology for dry eye disease from recent pathophysiologic findings ▶
DTS (Dysfunctional Tear Syndrome)
More accurately reflected pathophysiological events in dry ey
Severity levels of dry eye disease relied on symptoms & signs
Treatment recommendations for severity levels in a stepwise
approach
Easier approach for general eye care practitioners
Behrens A et al. Cornea 2006

10. International Dry Eye Work Shop (2007) Multi factorial disease
Symptoms of Discomfort & Visual Disturbance
Tear Film Instability
Results in
Multi factorial disease
Increased Osmolarity
of the Tear Film
Accompanied by
Inflammation
Of the Ocular Surface
Dry eye 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.
It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface.
The Definition and Classification of Dry Eye Disease: Report of the definition and classification subcommittee of the international Dry Eye Workshop(2007) The Ocular Surface 2007;5:75-92

12. Classification of Dry Eye
National Eye Institute (1994)

13. Delphi Panel Dry Eye Classification
Dysfunctional Tear Syndrome
With Lid Margin Disease
Tear Distribution
Without Lid Margin Disease
Anterior
Posterior
Conjunctivochalasis
Lid and Lash Malposition
Elevated Surface Lesion
Reduced or Incomplete Blinking
Others
Severity Level I
Severity Level II
Severity Level III
Severity Level IV
Behrens A et al., Cornea 2006;25:

14. Delphi Panel Dry Eye Classification
Level Sign & Symptom
I Mild to moderate symptoms
Mild to moderate conjunctival staining
Unstable tear film
II Visual signs
Mild corneal punctate staining
Conjunctival staining
III Severe symptoms
Marked corneal punctate staining
Central corneal staining
Filamentary keratitis
IV Severe corneal staining, erosions
Conjunctival scarring

15. International Dry Eye Work Shop (2007)
3 Classification
A. Etiopathogenic
B. Causative mechanism
C. Severity
Pflugfelder SC, et al, The Ocular Surface, 2007

16. Etiopathogenic Classification
2007 DEWS
DRY EYE
Aqueous deficient
Evaporative
Sjogran Syndrome Dry eye
Intinsic
Extrinsic
Non-Sjogren Dry eye
Meibomian Oil Deficiency
Vit.A Deficiency
Topical Drugs Preservatives
Primary
병인적 분류
Lacrimal Dificiency
Disorders of Lid Aperture
Secondary
Contact Lens Wear
Lacrimal G.
Duck Obstruction
Low Blink Late
Ocular Surface Disease (ex.Allergy)
Reflux block
Drug Action Accutane
Systemic drugs

17. Causative Mechanism of Dry Eye

18. Severity Classification
2007 DEWS
The Definition and Classification of Dry Eye Disease: Report of the definition and classification subcommittee of the international Dry Eye Workshop(2007) The Ocular Surface 2007;5:75-92

20. Delphi Panel Treatment Guideline
Eliminate Environmental/Drug Factors
Preserved Tears
Control Allergy
Dietary Modification (↑ Omega-3,6 FA)
LEVEL 1
Unpreserved Tears
Gels / PM Ointment
Cyclosporin A
Steroids
Secretagogues
LEVEL 2
Oral Tetracyclines
Autologous Serum
Punctal Plugs (after inflammation controlled)
LEVEL 3
Systemic Immunosuppressives
Topical Vitamin A
Contact Lenses
Moisture Goggles
Surgery (tarsorrhapy, AMT)
LEVEL 4

21. 2007 DEWS Treatment Guideline
Eliminate Environmental/ Dietary Modification
Elimination of offending systemic medications
Artificial tear substitutes, gels/ointments
Eye lid therapy
LEVEL 1
Anti-inammatories (Cyclosporin A, Steroids)
Tetracyclines (for meibomianitis, rosacea)
Punctal plugs
Secretogogues
Moisture chamber spectacles
LEVEL 2
Serum
Contact lenses
Permanent punctal occlusion
LEVEL 3
Systemic anti-inammatory agents
Surgery
(lid surgery, tarsorrhaphy; mucus membrane, salivary gland, amniotic membrane transplantation)
LEVEL 4

22. One treatment used most frequently for dry eye
Nichols JJ, CLSO, 2010

23. Treatment Guideline
한국형 가이드라인에 의한 분류 (가안)

24. Treatment Guideline
한국형 가이드라인에 의한 분류 (가안)

25. Treatment Guideline
한국형 가이드라인에 의한 분류 (가안)

26. NEI / Industry workshop
건성안의 개념 및 치료방침의 변화
눈물샘의 기능적 단위
NEI / Industry workshop
/ Delphi Panel
안구표면 시스템
Ocular Surface System
Dry Eye Workshop
개념의 변화
FROM TO
염증요소를 제거
눈물성분의 자연적인 생성을 자극
- 안구표면상피의 건강과 방어기능
을 유지
단순히 인공누액으로 안구표면에
수분을 공급, 윤활작용을 호전
Paradigm Shift
Management & Therapy of Dry Eye Disease. The Ocular Surface 2007;5:

28. Molecualr Mechanism of Ocular Surface Disease in Dry Eye

29. Causative Mechanism of Dry Eye

30. Hyperosmolarity in Tear Fluid
Hyperosmolarity has been recognized as a key factor in the pathogenesis of keratoconjunctivitis sicca (KCS) for decades
Elevated tear fluid osmolarity has been referred to as the “gold standard” for diagnosis of dry eye
Farris RL. Tear osmolarity--a new gold standard? Adv Exp Med Biol. 1994;350:
The exact mechanism by which hyperosmolarity induced pathologic changes and irritation symptoms remained a mystery

31. Tear Osmolarity – A New Gold Standard?
R. Linsy Farris, Adv Exp Med Biol. 1994;350:

32. Hyperosmolarity and Inflammation
Hyperosmolarity has been reported to significantly increase production of
inflammatory cytokines (such as IL-1)
chemokines (such as IL-8)
in human peripheral blood leukocytes,
bronchial epithelial cells
Shapiro L, Dinarello CA. Hyperosmotic stress as a stimulant for proinflammatory cytokine production. Exp Cell Res. 1997;231(2):
Hashimoto S, Matsumoto K, Gon Y, Nakayama T, Takeshita I, Horie T. Hyperosmolarity-induced interleukin-8 expression in human bronchial epithelial cells through p38 mitogen-activated protein kinase. Am J Respir Crit Care Med. 1999;159(2):

33. 산악인 오은선 - 히말라야 14좌 등반 - 카첸중가 (8586m)?
경청해 주셔서 감사합니다.