Tear Dysfunction and the Cornea: LXVIII Edward

Jackson Memorial Lecture

STEPHEN C. PFLUGFELDER

● PURPOSE: To describe the cause and consequence of complex and highly regulated system to produce and
tear dysfunction–related corneal disease. distribute tears.
● DESIGN: Perspective on effects of tear dysfunction on Tear dysfunction is one of the most prevalent medical
the cornea. conditions, affecting tens of millions of patients worldwide.
● METHODS: Evidence is presented on the effects of tear Tear dysfunction is a more encompassing term than dry eye
dysfunction on corneal morphology, function, and for tear-associated disorders of the ocular surface and
health, as well as efficacy of therapies for tear dysfunc- cornea because it encompasses changes in tear composition
tion–related corneal disease. rather than tear volume.1 Tear dysfunction has long been
● RESULTS: Tear dysfunction is a prevalent eye disease recognized to cause corneal epithelial disease that can
and the most frequent cause for superficial corneal decrease visual performance and cause ocular irritation.
epithelial disease that results in corneal barrier disrup- Mechanisms responsible for these pathologic changes were
tion, an irregular optical surface, light scattering, optical poorly understood until evidence from recent clinical
aberrations, and exposure and sensitization of pain- studies and animal models indicated that altered tear
sensing nerve endings (nociceptors). Tear dysfunction– composition causes dysfunction, accelerated death, and
related corneal disease causes irritation and visual detachment of the superficial epithelium, leading to an
symptoms such as photophobia and blurred and fluctu- irregular corneal surface, an unstable tear layer, and hyper-
ating vision that may decrease quality of life. Dysfunc- esthesia of the corneal nerve endings. These changes in
tion of 1 or more components of the lacrimal functional the superficial cornea can significantly impact quality of
unit results in changes in tear composition, including life and productivity in patients suffering from tear dys-
elevated osmolarity and increased concentrations of ma- function. I provide here my perspective on the function of
trix metalloproteinases, inflammatory cytokines, and tears on maintaining corneal health, the impact of tear
chemokines. These tear compositional changes promote dysfunction on the cornea, and consequences of tear
disruption of tight junctions, alter differentiation, and dysfunction–related corneal disease on patient well-being
accelerate death of corneal epithelial cells. based on published evidence and research I have per-
● CONCLUSIONS: Corneal epithelial disease resulting formed over the past 25 years.
from tear dysfunction causes eye irritation and decreases
visual function. Clinical and basic research has improved
understanding of the pathogenesis of tear dysfunction– VISION STARTS AT THE TEAR LAYER
related corneal epithelial disease, as well as treatment
outcomes. (Am J Ophthalmol 2011;152:900 –909. THE TEAR/CORNEAL EPITHELIAL COMPLEX IS THE MAJOR
© 2011 by Elsevier Inc. All rights reserved.) light-refracting surface of the eye, accounting for approx-
imately 65% of the optical power of the eye.2 A smooth

T
HE CORNEA IS A TRULY UNIQUE OPTICALLY CLEAR and stable tear layer is essential for maintaining high-
tissue, devoid of blood vessels, that relies on tears to quality vision between blinks. Ultrastructural, biochemi-
maintain a moist, smooth, and lubricated surface in cal, and functional studies show that the precorneal tear
the face of near-constant exposure to ambient environ- layer is a gel composed of soluble mucus secreted by the
mental conditions during waking hours. Additionally, the conjunctival goblet cells and fluid and proteins secreted by
tears provide myriad factors that protect the cornea from the lacrimal glands.3– 6 This hydrophilic gel moves over
microbial infection and the sight-threatening effects of the membrane mucins (glycocalyx) on the superficial
excessive inflammation or prolonged wound healing. To corneal epithelial cells and serves as a medium to refresh
maintain corneal clarity and quality vision, humans have a the tear components and clear debris. The precorneal tear
layer provides a smooth coating over the irregular micro-
plicae on apical corneal epithelia cells. The normal tear
Accepted for publication Aug 23, 2011. film remains stable for the entire interblink interval,
From the Cullen Eye Institute, Department of Ophthalmology, Baylor although the precorneal layer has been observed by optical
College of Medicine, Houston, Texas.
Inquiries to Stephen C. Pflugfelder, Cullen Eye Institute, 6565 Fannin, coherence tomography (OCT) to gradually thin at a rate of
NC 205, Houston, TX 77030; e-mail: stevenp@bcm.edu 4 ␮m/minute because of evaporation and the pull of

900 © 2011 BY ELSEVIER INC. ALL RIGHTS RESERVED. 0002-9394/$36.00

doi:10.1016/j.ajo.2011.08.023
 through dilution and removal through the nasolacrimal
duct system. Lipids secreted by the meibomian glands
retard tear evaporation.

TEAR DYSFUNCTION: A MAJOR

CLINICAL PROBLEM
TEAR DYSFUNCTION OCCURS WHEN THE LACRIMAL FUNC-
tional unit is no longer able to maintain a stable precorneal
tear layer. It may develop from dysfunction or disease of 1
FIGURE 1. Inferior tear meniscus measured by optical coher- or more components of the lacrimal functional unit. Tear
ence tomography (OCT) just before (Left) and 1 second after dysfunction is one of the most prevalent eye conditions.
(Right) a blink. Blinking decreased the tear meniscus area by Epidemiologic studies performed worldwide on different
two-thirds through upward pull over the cornea and lacrimal populations and using a variety of diagnostic criteria have
drainage.
reported the prevalence to range from 2% to 14.4%
depending on the study population and diagnostic crite-
ria.13–19 This translates to a prevalence of tear dysfunction
gravity toward the inferior meniscus.7 The precorneal tear in between 6 and 43.2 million people in the United States.
layer is replenished from the reservoir of tears in the A number of risk factors for dry eye have been identified.
inferior tear meniscus by blinking. This meniscus contains Age is perhaps the biggest risk factor, with the prevalence
75% to 90% of the tear volume (Figure 1).7,8 increasing in both men and woman with every decade of
To maintain continuous unobstructed vision, the eye is life over the age of 40, with a greater prevalence in women
open 92% of the time, with a blink rate of 15 times per than men at every age.18,19 Other risk factors identified
minute. This renders the cornea the most exposed mucosal include contact lenses,20,21 higher dietary consumption of
surface in the body. Thus, the corneal surface is presented n-6 to n-3 essential fatty acids,22 diabetes mellitus,16,17
with the challenge of resisting desiccation and maintaining cigarette smoking,16,23 prolonged video display viewing,21
a smooth optical surface during inter-blink intervals. It and low-humidity environments.24 Patients with tear dys-
must also be capable of surviving environmental, occupa- function typically report irritation symptoms including
tional, and recreational desiccating stress. To maintain foreign body sensation, burning, and dryness, as well as
clarity, the cornea must be resistant to microbial invasion vision-related symptoms such as photophobia and blurred
and be capable of initiating rapid, scar-free healing after and fluctuating vision. These symptoms may decrease
wounding. Because the cornea lacks blood vessels to supply quality of life in afflicted patients. In fact, the impact of
the antimicrobial defense and wound-healing factors nec- tear dysfunction on quality of life was rated to be equiva-
essary to combat these challenges, it depends on the tears lent to unstable angina using utility assessments.25 In some
to deliver them. Humans have highly complex tear- cases, the consequences of tear dysfunction can be devas-
secreting apparatus that we have termed the Lacrimal tating and result in functional and occupational disability.
Functional Unit (LFU), to maintain a stable precorneal tear The majority of the symptoms of tear dysfunction result
film (Figure 2).9 The LFU consists of an afferent compo- from corneal epithelial disease. Tear dysfunction has been
nent of trigeminal nociceptors in the cornea and ocular recognized for over a century as the major cause of superficial
surface that synapse in the brainstem with autonomic and corneal epithelial disease.26 It is now recognized that this
motor efferent nerves, as well as higher-order sensory epitheliopathy reduces corneal barrier function, causing an
neurons. Autonomic nerve fibers, primarily cholinergic, irregular optical surface, light scattering, optical aberrations,
have been found to innervate the meibomian glands, and exposure and sensitization of corneal nociceptors.
conjunctival goblet cells, and main and accessory lacrimal
glands.10 –12 Motor efferent fibers stimulate the orbicularis
oculi muscle to initiate blinking to express lipid secretions CHANGES IN TEAR COMPOSITION
from the meibomian glands, spread tears over the corneal AND CORNEAL EPITHELIAL DISEASE
surface, and direct them into the lacrimal puncta.
Tears contain a biochemically complex mixture of LACRIMAL GLAND DISEASE, MEIBOMIAN GLAND DISEASE,
factors (Table 1) that are produced by the lacrimal glands and reduced tear clearance from ocular surface diseases
and ocular surface epithelium to lubricate, support, pro- such as conjunctivochalasis have been reported to alter
tect, and heal the cornea (Figure 3). Reflex tear secretion tear composition (Table 2). Conditions causing dysfunc-
and blinking clear proteases and inflammatory mediators tion of the lacrimal gland, such as Sjögren syndrome, result
produced by the surface epithelium and resident immune in significantly decreased concentrations of certain pro-
cells that are capable of causing corneal epithelial disease teins and growth factors that are secreted by lacrimal

VOL. 152, NO. 6 TEAR DYSFUNCTION AND THE CORNEA 901

FIGURE 2. Integrated Lacrimal Functional Unit (LFU) that regulates secretion and delivery of tears to the cornea and ocular
surface. Nociceptors in the cornea (yellow) synapse with autonomic, motor, and higher sensory neurons in the brainstem that
innervate the tear-producing glands and orbicularis muscle to initiate blinking. Reprinted with permission from Beuerman R,
et al.116

TABLE 1. Role of Tear Components in Corneal Health

Role Component References

Lubrication MUC1, MUC4, MUC16, 101-103

MUC5AC
Wound healing EGF, substance P, TGF-␤ 104-106
Antimicrobial Lactoferrin, lysosyme, 107-111
defense defensins (␣ and ␤),
IgA
Anti-inflammatory IL-1RA, TGF-␤2 37, 106, 112
Protease TIMP1, SLPI 43, 113
inhibitors

EGF ⫽ epidermal growth factor; IL-1RA ⫽ interleukin 1

receptor antagonist; MUC ⫽ mucin gene; SLPI ⫽ secretory
leukocyte peptidase inhibitor; TGF⫽ transforming growth factor;
TIMP1 ⫽ tissue inhibitor of matrix metalloproteinase 1.

FIGURE 3. The precorneal tear layer contains factors pro-

acinar cells into tears, including lactoferrin and epidermal duced by the lacrimal glands, conjunctval goblet cells, and
growth factor (EGF).27,28 Reduced tear EGF concentration surface epithelium that lubricate (mucins), heal (epidermal
was found to correlate with severity of corneal fluorescein growth factor [EGF]), and protect the cornea from infection
staining in patients with tear dysfunction.28 Exposure of (lactoferrin, defensins, IgA) and excessive inflammation (inter-
the corneal epithelium to increased osmolarity or to leukin 1 receptor antagonist [IL-1RA], transforming growth
certain inflammatory/immune cytokines has been found to factor beta [TGF-␤], and tissue inhibitor of matrix metallopro-
promote inflammation, abnormal differentiation, acceler- teinase 1 [TIMP1]). MMP-9 ⴝ matrix metalloproteinase 9.
ated detachment, and programmed death (apoptosis) of

902 AMERICAN JOURNAL OF OPHTHALMOLOGY DECEMBER 2011

 transcriptional activation of genes encoding inflammatory,
TABLE 2. Tear Composition Changes Associated With matrix metalloproteinase (particularly MMP-9), and pro-
Corneal Epithelial Disease apoptotic factors.33,34
MMP-9 has been found to regulate physiological shed-
Tear Component Change Reference
ding of the corneal epithelium through lysis of the mem-
Sodium ion 1 osmolarity 114 brane-spanning tight junction protein occludin.35,36 In
Growth factor 2 EGF 28, 83 eyes with normal tear production, MMP-9 exists predom-
Cytokine/chemokine 1 IFN-ϒ, IL-1, IL-6, 28, 83 inantly in a latent inactive form and the low levels of
IL-8, MIP-1␣
mature MMP-9 are bound to its physiological inhibitor,
Protease MMP-9 40, 93, 115
tissue inhibitor of matrix metalloproteinase 1 (TIMP1).37,38
EGF ⫽ epidermal growth factor; IFN- ␥ ⫽ interferon gamma;
MMP-9 activity increases in the closed eye during sleep
IL ⫽ interleukin; MIP-1␣ ⫽ macrophage inflammatory protein 1 when tear production and clearance decrease.39 A diurnal
alpha; MMP-9 ⫽ matrix metalloproteinase 9. increase in MMP-9 expression was found to contribute to
controlled extracellular cleavage of junctional complexes
in the apical corneal epithelium in the Xenopus cornea
and it may make a similar contribution to physiological
turnover in the human cornea (Wiechmann AF, Pflug-
felder SC, Howard E. IOVS 2011 ARVO Abstract 303).
MMP-9 activity on the ocular surface increases in eyes
with tear dysfunction because of increased production by
stressed epithelial cells and infiltrating leukocytes, as well
as increased activity of its physiological activators (eg,
MMP-3) and reduced tear concentrations of TIMPs.40 – 43
Increased MMP-9 activity accelerates detachment of apical
corneal epithelium, exposing less mature subapical epithelial
cells and nociceptors, as shown in Figure 5. Furthermore,
loose epithelium, decreased surface lubrication, and friction
from blinking exacerbates the problem and may promote
FIGURE 4. Tear dysfunction–related alterations in tear com- development of filamentary keratitis.44 – 46 Disruption of the
position, including increased osmolarity and inflammatory cy-
apical barrier can cause irritation and reduce visual perfor-
tokines produced by epithelial cells (IL-1 and TNF-␣) and
mance, as discussed below. Pathways mediated by the stress
activated CD4ⴙ T cells (IFN-␥ and IL-17), activate the c-jun
n-terminal kinase (JNK) and nuclear factor ␬B (NF-␬B) stress kinase JNK2 were found to be primarily responsible for the
signaling pathways, leading to transcription of stress genes such MMP-mediated corneal barrier disruption in experimental
as inflammatory cytokines and chemokines, matrix metallopro- dry eye.47 JNK2 has been reported to have a similar function
teinases (MMPs), pro-apoptotic factors, and cornified envelop in osmotically induced barrier disruption in the colonic
precursor proteins. IFN-␥ ⴝ interferon gamma. epithelium.48
In addition to the ocular surface epithelium, inflamma-
tory mediators produced by inflammatory/immune cells
the corneal epithelium (Figure 4). Elevated tear osmolar- that reside on the ocular surface or that are recruited to the
ity, primarily attributed to increased Na⫹ ion concentra- conjunctival epithelium, particularly CD4⫹ T cells, were
tion, is a common feature of tear dysfunction caused by found to participate in the development of corneal epithe-
lacrimal and meibomian gland disease.29 The mean osmo- lial disease in dry eye. Our group has found that exposure
larity measured in tears— collected from the inferior me- to desiccating stress recruits activated CD4⫹ T cells of the
niscus in eyes with tear dysfunction— has been found to be Th1 and Th17 lineages to the ocular surface.49,50 Inter-
about 20 to 40 mOsm/L greater than the normal tear film, feron gamma (IFN-␥), the signature cytokine produced by
ranging from 314 to 365 mOmol/L29; however, osmolarity Th1 cells, was found to induce apoptosis of the cornea and
in areas of break-up of the precorneal tear layer has been conjunctival epithelia, while interleukin 17 (IL-17) pro-
calculated to be much higher and consistent with values of duced by Th17 cells stimulated production of MMPs 3 and
560 mOsm/L measured in tear samples collected from the 9 by the corneal epithelium.50 –52 The corneal epithelium
entire ocular surface of mice with experimentally induced has been found to express receptors for both IFN-␥ and
dry eye.30 –32 Exposure to a high-osmolality environment IL-17.50,52
has been identified as a considerable stress to the corneal Desiccation, osmotic stress, and the inflammatory cyto-
epithelium, resulting in activation of the mitogen- kines IL-1 and IFN-␥ can promote skin epidermal-like
activated protein kinase (MAPK) and nuclear factor ␬B differentiation in the corneal epithelium with increased
(NF-␬B) stress signaling pathways in these cells (Figure 4). production of cornified envelope precursors that are absent
These pathways initiate a cascade of events, including or produced at low levels in unstressed corneal epithelial

VOL. 152, NO. 6 TEAR DYSFUNCTION AND THE CORNEA 903

FIGURE 5. Reduced tear production and desiccation in experimental dry eye in mice leads to proteolytic dissolution of tight
junction protein occludin and accelerated desquamation in the apical epithelial cells (Top), resulting in exposure of less
differentiated subapical epithelia and activated nociceptors that signal discomfort from the ocular surface (Bottom).

cells.49,53 Furthermore, exposure to high osmolarity acti- that increase firing as the temperature decreases from 34 to
vates intrinsic apoptotic pathways in corneal epithelial 24 C have been shown to regulate basal tear flow by the
cells that can lead to accelerated turnover of the apical lacrimal gland.59 More rapid corneal cooling in eyes with
epithelium.54 Increased numbers of cornifying, dead, and tear dysfunction and accelerated tear break-up likely re-
detaching epithelial cells may be responsible for the sults in increased nerve firing that may be interpreted as
increased number of opaque corneal epithelial cells that eye discomfort.60,61 Studies evaluating corneal sensitivity
have been observed by confocal microscopy and metaplas- in dry eye have reported conflicting results of either
tic cells noted in conjunctival impression cytology of heightened or reduced sensitivity. Hyperesthesia has been
patients with tear dysfunction.55–57 observed in several studies using a gas esthesiometer,62,63
while studies testing mechanical sensitivity with a nylon
monofilament have generally found reduced sensitivity to
CLINICAL CONSEQUENCES OF TEAR this mechanical stimulus.64,65 The conflicting findings of
DYSFUNCTION ON THE SUPERFICIAL hyperesthesia or hypoesthesia in eyes with tear dysfunction
CORNEA may be attributed to the type of test stimulus applied
or corneal nerve degeneration that may develop in eyes
THE PRINCIPAL CLINICAL MANIFESTATION OF TEAR DYS-
with long-standing tear dysfunction, particularly Sjögren
function–related superficial corneal epithelial disease is eye
irritation. Typical symptoms consist of dryness, foreign syndrome.66,67
body sensation, and burning. Patients often complain of Many patients with corneal epitheliopathy complain of
exquisite sensitivity to wind or drafts from air conditioning photosensitivity that in some cases can be severe and
vents. While the mechanisms responsible for these irrita- disabling, forcing them to wear tinted glasses and avoid
tion symptoms are not fully understood, it appears they are bright lights. This symptom may be attributed in part to
attributable in large part to greater exposure of corneal light scattering from the irregular tear film and superficial
nociceptors to environmental stimuli, as well as sensitiza- corneal epithelium. Videokeratoscopic surface regularity
tion of these nerve endings by inflammatory mediators. indices have found greater surface irregularity in eyes with
Rosenthal and associates have proposed the term “corneal tear dysfunction that correlated with the severity of cor-
neuralgia” to describe the heightened corneal sensitivity neal fluorescein staining.68 Serial corneal topographic
associated with tear dysfunction.58 Transient receptor measurements taken of the open eye after a blink have
potential cation channel subfamily member 8 (TRPM8) observed a more rapid increase of corneal surface irregu-
ion channels in cold receptors in the corneal epithelium larity than eyes with normal tear function and the rate of

904 AMERICAN JOURNAL OF OPHTHALMOLOGY DECEMBER 2011

change corresponded to the severity of corneal epithelial costeroids, tetracyclines, and n-3/n-6 essential fatty acids
disease.69,70 have also been found to decrease production of a variety of
Corneal epithelial disease may also reduce optical per- inflammatory mediators and improve corneal epithelial
formance. Many patients with tear dysfunction complain disease.87–92 The efficacy of corticosteroids and tetracy-
of fluctuating vision that may improve following instilla- clines on corneal barrier function may be attributable to
tion of artificial tears. Often patients with tear dysfunction their ability to inhibit MMP activity.89,90,93 Compounds
have normal visual acuity measured by conventional meth- that inhibit leukocyte migration into the ocular surface
ods; however, reduced visual performance has been found tissues in dry eye, such as integrin ␣4␤1 (VLA-4) or
with more sophisticated measures of visual function. Pa- chemokine receptor 2 (CCR2) antagonists, were found to
tients with corneal epithelial disease were noted to have improve corneal barrier function in animal models of dry
greater reduction in contrast sensitivity and low-contrast eye.94,95
visual acuity than eyes with normal tear function.40,71–74 A For severe corneal epitheliopathy from tear dysfunction,
number of studies have reported increased levels of higher- the prosthetic replacement of the ocular surface ecosystem
order aberrations, particularly coma, in eyes with tear (PROSE), a specially designed scleral-bearing contact lens
dysfunction.75,76 These alterations in visual quality lead to with a fluid-filled reservoir over the cornea, has proven to
a reduction in functional visual acuity.77,78 be an excellent option for improving irritation symptoms
Tear dysfunction can directly or indirectly increase the and visual acuity.96,97 The fluid-filled reservoir shields the
risk for developing microbial keratitis. Tear fluid contains cornea from blink trauma, noxious environmental stimuli,
factors that inhibit microbial attachment and invasion and inflammatory mediators in the tears. The body-
into the corneal epithelium.79 Corneal epitheliopathy temperature saline reservoir also prevents corneal cooling
from severe tear dysfunction has also been identified as a and nerve firing that occurs in the inter-blink intervals.
risk factor for microbial keratitis.80,81 Patients may experience almost immediate relief in pho-
Eyes with reduced tear clearance associated with mei- tophobia and irritation symptoms after placing the device
bomian gland disease have been reported to have increased on the cornea. Compared to artificial tears, autologous
levels of tear EGF and VEGF that has been found to be serum (20%) was found to significantly improve corneal
associated with subepithelial fibrosis and peripheral epithelial disease in patients with severe dry eye.98 Injec-
vascularization.82,83 tion of botulinum toxin A in the lid has been found to
decrease blink force and to improve superior limbic kera-
toconjunctivitis and filamentary keratitis.99,100
APPROACHES TO TREAT TEAR
DYSFUNCTION–RELATED CORNEAL
DISEASE DISCUSSION
INCREASED KNOWLEDGE REGARDING THE CELLULAR AND THIS PERSPECTIVE HAS DESCRIBED THE EFFECTS OF TEAR
molecular mechanisms of tear dysfunction–mediated cor- dysfunction on the cornea. Corneal disease resulting from
neal epithelial disease has prompted use of therapies that tear dysfunction is one of the most common eye conditions
target disease-related factors and has generated buzz in the and a major cause for patients seeking eye care. Irritation
pharmaceutical industry about topical use of targeted and visual disturbance from superficial corneal epithelial
immunomodulators. Over the past decade there has been a disease can greatly impact productivity and quality of life
trend toward increased use of anti-inflammatory therapies in afflicted patients. Changes in tear composition appear to
to improve comfort, corneal smoothness, and barrier func- be primarily responsible for the corneal epithelial barrier
tion. Cyclosporin A (CsA), the only FDA-approved ther- disruption and activation of stress pathways in the corneal
apy for tear dysfunction, inhibits T-cell activation and epithelium that lead to an irregular and poorly lubricated
production of the Th cytokines IFN-␥ and IL-17.84,85 corneal surface. Greater understanding of the mechanisms
Topical CsA significantly reduced severity of corneal responsible for these pathologic changes has led to new
fluorescein staining after 4 and 6 months of use.86 Corti- treatment options and improved outcomes.

THE AUTHOR HAS COMPLETED AND SUBMITTED THE ICMJE FORM FOR DISCLOSURE OF POTENTIAL CONFLICTS OF INTEREST AND
indicates consulting fees from Allergan, Alcon, and GlaxoSmithKline, and honoraria from Allergan. Publication of this article was supported by National
Institute of Health (Bethesda, Maryland) grants EY11915 and RO1EY018090 to S.C.P.; and grants from Research to Prevent Blindness (New York, New York),
The Oshman Foundation (Houston, Texas), The William Stamps Farish Fund (Houston, Texas), The Hamill Foundation (Houston, Texas), and Allergan, Inc
(Irvine, California). The author is responsible for writing and all aspects of preparation of this manuscript. This work would not have been possible without
the contributions of the author’s mentors and collaborators: Dan B. Jones, Edward W.D. Norton (posthumous), John Clarkson, Richard K. Parrish, Richard K.
Forster, William W. Culbertson, Sally Atherton, Michael E. Stern, Scheffer Tseng, De-Quan Li, Andrew J. Huang, and Cintia S. de Paiva.
Given the editorial perspective nature of this manuscript, there are no issues related to IRB approval; HIPAA compliance; Clinical Trials registration,
number, and location; or Institutional Animal Care and Use Committee guidelines.

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 Biosketch
Stephen C. Pflugfelder, MD, graduated from Colgate University summa cum laude and SUNY Upstate Medical University
Syracuse where he was elected to AOA. He did his Ophthalmology residency at Baylor College of Medicine where he
served as Chief Resident in 1984. After completing a Cornea fellowship at the Bascom Palmer Eye Institute of the
University of Miami School of Medicine, he was appointed to the faculty of the Bascom Palmer Eye Institute in 1985 and
was promoted to Professor in 1998. He joined the faculty of the Cullen Eye Institute of Baylor College of Medicine as a
Professor and Director of the Ocular Surface Center in July 2000. He was awarded the James and Margaret Elkins Chair
in Ophthalmology at the Baylor College of Medicine in 2001. Dr Pflugfelder has published over 190 peer-reviewed articles
and over 45 book chapters and monographs, primarily in the field of cornea diseases and surgery. He served as a co-editor
for Dry Eye and Ocular Surface Disorders, a comprehensive textbook on the subject that was published in 2004. He was
included in the last five editions of “Best Doctors in America”. He received the American Academy of Ophthalmology
Senior Achievement Award in 2000 and a Research to Prevent Blindness Senior Investigator Award in 2002. He served
as Chairman of the American Academy of Ophthalmology Lifelong Education for Ophthalmologists Committee and as
a member of the American Academy of Ophthalmology Preferred Practice Pattern Committee on Corneal and Ocular
Surface diseases. He serves on the Editorial Boards of the journals American Journal of Ophthalmology, Cornea, Investigative
Ophthalmology and Visual Science and The Ocular Surface. Dr Pflugfelder will present the Edward Jackson Memorial Lecture
at the 2011 American Academy of Ophthalmology. His research interests include the role of inflammation in dry eye and
corneal bioengineering.

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