TUGAS JOERNAL READING

STASE MATA

PERIODE 2 Desember – 4 Januari 2020

KEPANITERAAN KLINIK SMF BAGIAN MATA

RUMAH SAKIT UMUM DAERAH H. ABDUL MOELOEK
FAKULTAS KEDOKTERAN UNIVERSITAS LAMPUNG
2020

Corneal Ulcer:
Diagnosis and Management
Prashant Garg MS
Gullapalli N Rao MD
Sight Savers’ Corneal Training Centre
L V Prasad Eye Institute
L V Prasad Marg
Banjara Hills
Hyderabad 500 034, India
Introduction
C orneal scar is a significant cause of
visual impairment and blindness in
the developing world. Corneal infections
are responsible for a large proportion of
this scarring. A review of the data on indi-
cations for corneal transplantation in the
developing world revealed that corneal
scar was the most common indication
(28.1%), of which keratitis accounted for
50.5%. Besides this, about 12.2% of all
grafts were done for active infectious ker-
atitis.1 Thus suppurative keratitis and its
complications constitute important causes
of ocular morbidity, particularly in the
developing world.
Almost any organism can invade the
corneal stroma if the normal corneal
defence mechanisms, i.e., lids, tear film
and corneal epithelium are compromised.
While viral infections are the leading
cause of corneal ulcer in the developed
nations (with Acanthamoeba infection in
contact lens wearers), bacteria, fungi and
Acantha- moebae are important
aetiological agents in the developing
world. The spectrum of corneal pathogens
shows a wide geograph- ical variation. At
L V Prasad Eye Institute, Hyderabad,
71.9% of all cases of ulcerative keratitis
were culture positive. Of the cul- ture
positive cases 63.9% were bacterial, 33%
were fungal, 2.1% were parasitic, and
6.2% were due to mixed infection. Various
organisms isolated from cases of
infectious keratitis are shown in Table 1.
Fig.2. Ring infiltrate in fungal keratitis
Photo: P Garg & G N Rao
In this article we focus on the diagnosis
and management of suppurative corneal
ulcer.
Diagnosis
A detailed history and thorough clinical
examination using the slit-lamp biomicro-
scope are important steps in the diagnosis
of corneal ulcer. Although clinical signs
may be insufficient to confirm infection, a
break in the continuity of the epithelium
associated with underlying stromal infil-
trate should be considered infectious
unless proved otherwise. Similarly, there
are no distinctive or exclusive signs to
identify the responsible organisms, but
clinical experience and careful slit-lamp
examination can point toward a probable
aetiological diagnosis in some cases.
Gram-positive cocci typically cause
localised round or oval ulceration with
greyish white stromal infiltrates having
distinct borders and minimal surrounding
stromal haze. Keratitis due to gram-nega-
tive bacteria typically follows a rapid
inflammatory destructive course charac-
terised by dense stromal suppuration and
hazy surrounding cornea with a ground
glass appearance. Fungal keratitis is usual-
ly characterised by a dry raised slough,
stromal infiltrate with feathery edges,
satellite lesions, and a thick endothelial
exudate. Acanthamoeba keratitis is charac-
terised by epithelial irregularities with
single or multiple stromal infiltrates in a
classical ring-shaped configuration. Severe
pain and radial keratoneuritis (i.e., inflam-
mation of the corneal nerves, seen as a
whitish outline of the corneal nerves) are
also characteristics of Acanthamoeba
infection.
Since the clinical appearance of suppu-
rative keratitis depends on many variables,
it is often difficult to arrive at an aetiologi-
cal diagnosis based entirely on slit-lamp
examination. For example, apart from
Acanthamoeba keratitis (Fig.1), the ring-
shaped infiltrate can be seen in fungal ker-
atitis (Fig.2), HSV (herpes simplex) kerati-
tis, and even in Pseudomonas keratitis.
Similarly, Nocardia keratitis presents clas-
sically with multiple small white infiltrates
arranged in a wreath pattern (Fig. 3), and it
can have fine filaments extending into the
surrounding cornea, similar to fungal kera-
titis. Pain out of proportion to the size of
infiltrate and radial keratoneuritis, classi-
cally described for contact lens-related
Review Article
Fig.1. Ring infiltrate in Acanthamoeba
keratitis
Photo: P Garg & G N Rao
Acanthamoeba keratitis, is rarely experi-
enced in non-contact lens related Acanth-
amoeba keratitis. The clinical picture is
often confused if the lesions are peripheral,
or advanced involving the entire cornea
(Fig. 4). Laboratory investigations are
therefore required if the causative organ-
ism is to be identified.
Laboratory Investigations
The laboratory procedures used in the
diag- nosis of infectious keratitis are based
on:
(a) direct visualisation of organisms in the
material.
(b) inoculation of material under appropri-
ate conditions to allow multiplication
of organisms.
Whenever a patient with infectious ker-
atitis presents, after detailed clinical exam-
ination, corneal scrapings are taken under
topical anaesthesia using a sterile No. 15
Bard Parker blade. Scrapings are taken
from the edges and base of the ulcer (see
Appendix). The material obtained is exam-
ined microscopically using Gram’s (see
Appendix) and Giemsa staining methods
and potassium hydroxide 10% or calcoflu-
or white preparation. Calcofluor white is a
fluorescent dye and requires a fluorescent
microscope. Lactophenol cotton blue stain
may also be used which does not require
a fluorescent microscope (see Appendix).
The material is also inoculated on various
solid and liquid media that facilitate the
Fig.3. Nocardia keratitis with multiple pin-
Community Eye Health Vol 12 No. 30 1999
head infiltrates and hypopyon Photo: P Garg & G N Rao
Corneal Ulcer
regarding the best option for community
scopy using Gram’s staining method and
potassium hydroxide (KOH) preparation is
simple and quick to perform and often
gives useful information for initial medical
management. Culture and sensitivity, on
the other hand, require more sophisticated
facilities.
Although the ophthalmic literature uni-
formly recommends that microbiological
investigations must be performed in all
Fig.4. Corneal destruction due to cases of infectious keratitis, these proce-
Pseudomonas infection dures require investment of a certain
Photo: P Garg & G N Rao
amount of time and expense by the oph-
thalmologist, the patient and ultimately the
growth of bacteria, fungi, and Acantha- medical system in general. A survey of
moeba. These include fresh blood agar, community ophthalmologists in southern
chocolate agar, Saburaud’s dextrose agar California showed that less than 20% of
(SDA), non-nutrient agar with an overlay corneal ulcers were treated in accordance
of Escherichia coli, thioglycolate broth and with textbook recommendations.2 Another
brain heart infusion broth (Fig. 5). These study found that less than 4% cases re-
media are incubated under appropriate quired a change in initial antibiotic therapy
atmospheric conditions and are examined based on an inadequate clinical response.3
daily for growth for at least seven days It has also been documented that there may
before a negative report is given. The be poor correlation between in vitro
growth on media is then identified antimicrobial sensitivity and in vivo clini-
and where appropriate is subjected to cal response. Consequently, there is some
an antimicrobial susceptibility test. Micro- controversy over the routine use of micro-
biological investigations (including anti-
microbial sensitivity testing) in the man-
Table 1: Various Isolates from Cases
agement of suppurative keratitis. Based on
of Infectious Keratitis. L V Prasad
the experience gained at the L V Prasad
Eye Institute: January 1991 – Eye Institute and a relatively higher inci-
December 1998 (n=2655) dence of fungal keratitis (33%) in the
Bacteria: n=1689 tropi- cal climate, we are of the opinion
Gram positive cocci that microscopic examination of corneal
Staphylococcus epidermidis32.4% scrap- ings using Gram’s staining
Staphylococcus aureus7.6% techniques and KOH (10%) preparation
Other staphylococci4.0% can provide useful guidance for initial
Streptococcus pneumoniae13.1% therapy in a case of suppurative keratitis.
-haemolytic streptococci5.3% Other
streptococci & micrococci 1.6% Treatment
Gram positive bacilli When treating a patient with suppurative
Corynebacterium 13.9% keratitis the clinician has 3 management
Bacillus 1.2% options:
Nocardia 1.7%
1. Complete microbiological work-up of
Mycobacterium 0.4%
Propionibacterium 1.2%
all ulcers, followed by initial therapy
based on the smear results;
Gram negative bacilli 2. Empirical therapy (based on previous
Pseudomonas 11.1% clinical experience) with one or more
Enterobacteriaceae 1.7% commercially available broad spectrum
Moraxella 1.4% antimicrobial agents; or
Aeromonas 0.4% 3. Microbiology work-up of severe ulcers
Acinetobacter 0.7% where the history or clinical findings
Haemophilus 0.8% suggest an atypical non-bacterial
F ngi: n=893 pathogen.
u Aspergillus 33.0% It is clear that option 1 is the best
Fusarium 35.1% approach for the tertiary referral practice,
Dematiaceous fungi 14.4% because most of the ulcers are severe or
Other hyaline fungi 16.4% caused by unusual or resistant organisms
Candida 1.0% that have failed to respond to initial thera-
Parasites: py. However, there is a lot of confusion
 Acanthamoeba
ophthalmologists.
22 A large proportion of
suppurative keratitis is caused by
bacteria (64%), most of which are
sensitive to broad spectrum antibiotics.
It is reason- able, therefore, to assume
that in small lesions that are away from
the visual axis and not associated with
risk factors for unusual organisms,
initial treatment may be started with a
broad spectrum antibiotic at frequent
intervals. These patients, how- ever,
need close daily follow up to make sure
the lesion is improving. At the earliest
evidence of deterioration the ulcer
should be subjected to a detailed
microbiology work-up or referred to a
centre where such facilities exist.
Treatment with a commercially
avail- able antibiotic that has a broad
spectrum of activity against gram-
negative and gram- positive organisms,
such as ciprofloxacin or ofloxacin,
seems to be the least expen- sive first
approach. However, there is a risk of
development of resistance particularly
with ciprofloxacin.
Microbiological investigations should
always be done for the following cases.
Severe ulcers (a rapidly progressing
infiltrate which is more than 6mm in
diameter or involves deeper stroma
or associated with imminent or actual
per- foration).
Cases where history and clinical
exami- nation suggest unusual non-
bacterial pathogens.
Initial treatment in Health
Community Eye theseVol
cases
12 No.should
30 1999 be
based on the microscopic examination.
Initial treatment in fungal keratitis is
usually started with natamycin (5%) sus-
pension administered half hourly. Various
antifungal agents used in the treatment of
keratitis are shown in Table 2.
For Acanthamoeba keratitis, treatment is
usually started with polyhexamethylene
biguanide (PHMB) 0.02% or
chlorhexidine 0.02% (Table 3). Antifungal
and anti- Acanthamoeba therapy is started
only when microbiological evidences
exists.
Fig.5. Various culture media used in
laboratory diagnosis of microbial keratitis
Photo: P Garg & G N Rao

Table 2: Antifungal
Agents used in
Keratitis
Polyenes
Nystatin Amphotericin B Natamycin
Pyrimidines
Flucytosine
Imidazoles
Clotrimazole Miconazole Ketoconazole
Fluconazole Itraconazole
Modification of therapy is primarily based
on clinical response to initial therapy and
is guided by the results of culture and
sensi- tivity tests.
Supplementary Treatment
Cycloplegic agents such as atropine sul-
phate 1%, homatropine 1% or cyclopento-
late 1% instilled three times a day reduce
ciliary spasm and produce mydriasis,
thereby relieving pain and preventing
synechiae formation.Anti-glaucomaagents
are used when intraocular pressure is high.
If required, oral analgesics for pain may
be used.
The role of topical corticosteroids in the
management of suppurative keratitis is
controversial and hence they are best
avoided.
Simple debridement of necrotic debris
in conjunction with intensive topical
therapy may help facilitate drug
penetration espe- cially of anti-fungal
agents.
Tissue adhesive using N-butyl cyano-
acrylate with a bandage contact lens is
useful in cases with marked thinning or
perforation less than 2mm.
Penetrating keratoplasty is performed in
cases with advanced disease at presenta-
tion where there is no response to medical
therapy or when a large perforation is pre-
sent.
Prevention
Although not always a preventable
disease, certain steps may help reduce the
potential- ly severe consequences of
suppurative ker- atitis.
 Community awareness of risk factors for
suppurative keratitis such as minor trau-
ma and the use of contaminated tradi-
tional eye solutions in the eye
 Early recognition and institution of
appropriate therapy by community
health workers or ophthalmologists
 Prompt referral of advanced cases to ter-
tiary eye care centres
Corneal Ulcer
Table 3: Anti-Acanthamoeba Agents
used in Keratitis
Antiseptic biocides
Chlorhexidine PHMB
Aminoglycosides
Neomycin Paromomycin
Diamidines
Dibromopropamidine Hexamidine
Suppurative keratitis is a sight-threaten-
ing disorder. Early clinical suspicion,
ratio- nal use of laboratory diagnostic
procedures and appropriate therapy can go
a long way towards reducing ocular
damage from this disorder.
References
1. Dandona L, Krishnan R, Janarathanan M et al.
Indications for penetrating keratoplasty in
India. Indian J Ophthalmol 1997; 45: 163–8.
2. McDonnell PJ, Nobe J, Gauderman WJ et al.
Community care of corneal ulcers. Am J
Ophthalmol 1992; 114: 531–8.
3. McLeod SD, Kolahdouz-Isfahani A, Rosamian
K et al. The role of smears, cultures and anti-
biotic sensitivity testing in the management of
suspected infectious keratitis. Ophthalmology
1996; 103: 23–8.

Herpes Simplex Virus Keratitis

Herpes simplex virus infection is an
important cause of corneal scarring and
visual impairment. The clinical features
and treatment of herpetic corneal ulcera-
tion were the subject of an early edition
of the Journal (J Comm Eye Health
1990; 3: 1–4).
Herpes simplex virus is found world-
wide, sometimes with devastating
effects (see photos), although Drs Garg
and Rao rightly indicate that in develop-
ing countries other causes of corneal
ulceration arerelativelymore common.
The subject of herpes simplex virus
keratitis is not addressed in this particu-
lar issue of the Journal.
Herpes simplex virus keratitis
Editor. (and stomatitis) in an African child
Photos: John Sandford-Smith

Eye Health Tel: 00 44 (0)171 608 6910. Fax: 00 44

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Managing corneal foreign bodies
in office-based general practice
Alison Fraenkel, Lawrence R Lee, Graham A Lee
Background
Patients with a corneal foreign body may first present
to their general practitioner (GP). Safe and efficacious
management of these presentations avoids sight-
threatening and eye- threatening complications.
Removal of a simple, superficial
foreign body without a slit lamp is within The Royal
Australian College of General Practitioners’ (RACGP’s)
curriculum and scope of practice. Knowing the relevant
procedural skills and indications for referral is equally
important.
OBJECTIVE
The objective of this article is to provide an evidence-
based and expert-based guide to the management of
corneal foreign bodies in the GP’s office.
Discussion
History is key to identifying patient characteristics
and mechanisms of ocular injury that are red flags for
referral. Examination techniques and methods of
superficial foreign body removal without a slit lamp
are outlined, as well as the procedural threshold for
referral to an ophthalmologist.
Dr Masresha Abuhay, Dean of Gonder
Medical College, Ethiopia received a copy
of Community Eye Health from the
Editor’s son, David McGavin
Photo: James Moult
FOCUS
‘T here’s something in my eye!’ This is a common
ophthalmic problem in the rooms of general practitioners
(GPs). The Royal Australian College of General
Practitioners’ (RACGP’s) 2016 curriculum includes ‘the
removal of a foreign body, including any residual corneal ulcer
or rust’ as a required skill.1 Variability of access to a slit lamp
is acknowledged by the RACGP. 2 However, safe and effective
initial assessment and management of corneal foreign bodies
can be carried out with a good history, examination and
intervention using readily available equipment.
History
A thorough history of symptoms, mechanism of injury, suspected
material involved, timing of the incident and an ocular history
will direct management approach. Symptoms include a foreign
body sensation, grittiness, irritation, pain, redness,
photophobia,
blurred vision and excessive watering of the eyes. A particular
inciting event will usually be recalled.
Metallic foreign bodies in the context of hammering or
drilling metal-on-metal (Figure 1A), particularly in the
absence of protective eyewear, may just embed in the corneal
surface but can penetrate the eye if travelling at sufficiently
high velocity.3,4 In the case of globe penetration, urgent
referral to the nearest emergency department with
ophthalmological care should occur.5 Foreign bodies involving
organic material, such as those
sustained while gardening, carry a high risk of infection and often
warrant referral. Seeds (Figure 1B), insect scales (Figure 1C) and
caterpillar setae are infrequent, but have well-described vision
threatening consequences.6
The time of the incident is important. A superficial foreign
body embedded earlier that day is particularly amenable to
removal in a GP’s office as there will be no encroaching
corneal epithelium and no rust ring. If the inciting event
occurred a few days prior, and there has been an increase in
pain, significant worsening of vision and diffuse conjunctival
redness (Figure 1D), then a corneal infection and/or
endophthalmitis are more likely and urgent referral is indicated.

Figure 1. Corneal foreign bodies
A. Metallic particle from drilling; B. Seed; C. Insect scale; D. Keratitis and
endophthalmitis from a contact lens
It is important to note any previous eye conditions.
Concurrent contact lens use is an indication for referral
because of the risk of severe infection with unusual organisms.
Do not commence antibiotics as microbiological specimens
may need to be taken. Take care to ensure that amblyopia or
pre-existing poor vision in an eye is not mistaken for a
reduction in visual acuity associated with a foreign body.
Examination
The equipment required for the office-based examination and
removal of a corneal foreign body is outlined in Box 1.
Visual acuity
This is the most important but often overlooked parameter to
document in the patient’s medical notes. If there are no available
hard copies of a Snellen chart, it is sufficient to use those
Box 1. Equipment for removal of a corneal foreign body
in a general practitioner’s office
• Snellen chart
• Bright light source (eg pen torch, ophthalmoscope or a medical
light on a stand or wall-mounted)
• Eyelid speculum (optional)
• Loupes (if available)
• Fluorescein strip or drops
• Topical anaesthetic drops (eg oxybuprocaine 0.4%)
• Cobalt blue light, from an ophthalmoscope or Wood’s lamp
• Sterile cotton tips
• Sterile normal saline
• Sterile 25G 16 mm hypodermic needle or 15 scalpel blade
CORNEAL FOREIGN BODIES
FOCUS
available via smartphone apps or downloaded from the internet.
Snellen charts do not have to be positioned at the traditional
3 m or 6 m if these distances are not achievable, as long as
the distance used and distance specified by the visual acuity
chart, particularly if it is from the internet, are recorded. A
drop of topical anaesthetic can be instilled to reduce
interfering photophobia. If the patient cannot see any letters,
move the chart closer. In the case of a greater visual deficit,
record whether the patient can ‘count fingers’ and the
distance at which this is possible. If their vision does not
permit them to
count fingers, record whether they can detect ‘hand movement’
or have ‘perception of light’ at a distance of 10 cm.
Conjunctiva, cornea, anterior chamber and pupils
These structures can be examined with a bright-focused
light, such as a pen torch, ophthalmoscope or loupes. An
ophthalmoscope provides a magnified view of these structures
when dialled to +10D and held at 10 cm.7
The location, size and depth of the corneal foreign body
should be noted, particularly if it is in the central pupillary
zone. Surrounding corneal opacity may indicate a rust ring,
burn, infection, oedema or scar tissue. Irregularities in pupil
shape may indicate a penetrating foreign body causing iris
incarceration.
Eyelid eversion
If there is no sign of penetration, the upper and lower eyelids
of both eyes should always be single everted (Figure 2A) to
examine for foreign bodies on the tarsal plate (Figure 2B),
and the upper lids double everted (Figures 2C, D) to look for
foreign bodies in the upper fornix. These can be easily
missed, causing
Figure 2. Eyelid eversion
A. Single eversion; B. Subtarsal foreign body; C. Double eversion of eyelid
with moist cotton tip; D. Side view of double eversion
the patient ongoing foreign body symptoms despite removal of
the corneal lesion.
Fluorescein
Fluorescein is used to detect any epithelial defect associated
with the foreign body. It can be instilled via a moistened strip
or as drops, and the ocular surface viewed with a cobalt blue
filter from an ophthalmoscope or a Wood’s lamp. Multiple
vertically orientated linear abrasions should raise suspicion of a
tarsal plate foreign body. The Seidel’s test using 2% fluorescein
can detect an aqueous leak that will occur in non–self sealing
corneal perforations.
Differential diagnosis
A corneal abrasion with no foreign body is a possible
alternative diagnosis. The cornea is densely innervated by free
nerve endings, which makes it difficult to distinguish between
an abrasion and a foreign body on the basis of symptoms alone.
Of 1155 consecutive patients presenting to a UK emergency
department with an ocular foreign body sensation, 157 (13.6%)
had a corneal abrasion only.8 If no foreign body can be found
in the GP’s office examination and the foreign body sensation
persists overnight, referral should be made for review of the
eye on a slit lamp.
Other differential diagnoses include Herpes simplex virus
(HSV) keratitis, exposure keratopathy, chemical exposure,
ultraviolet exposure or ‘welding flash’ and recurrent corneal
erosion syndrome.3,9 These can be differentiated on the basis of
history.
Investigations
Generally, a corneal foreign body does not require further
investigation. If there is suspicion of ocular penetration, an
orbital X-ray, including lateral and anterior–posterior views, or
computed tomography (CT) scan can be requested. Magnetic
resonance imaging (MRI) is avoided in case of metallic foreign
bodies.
Removal of the foreign body
Refer to the list of equipment in Box 1.
Anaesthetic and pupil dilator
Instil local anaesthetic into both eyes as this reduces
blepharospasm. Topical oxybuprocaine 0.4% takes
approximately 20 seconds to work and lasts for 20 minutes. A
drop of topical pupil dilator such a cyclopentolate 1%, if
available, can be helpful to reduce ciliary spasm after removal
of a foreign body. Avoid atropine as its effects of pupil dilation
and loss of accommodation can last for two weeks or more.10
Removal techniques
The choice of technique will depend on the nature of the foreign
body, remembering that whatever instrument is used, the eye
should be approached from the side within a plane less than 5
cm from the face. This is less confronting for the patient as they
will not be able to clearly focus on the object, and eliminates the
blink reflex caused by an object approaching the eye front-on.
Cotton tip removal
Superficial foreign bodies with no surrounding corneal
reaction can often be removed in a dabbing or nudging
motion with a cotton tip soaked with local anaesthetic or
saline.
Hypodermic needle (25G 16 mm) or 15 blade removal
Corneal thickness is 0.55 mm centrally, and thicker
peripherally, so the removal of superficial foreign bodies poses
a low risk for perforation if a safe technique is observed. It can
be helpful to bend the tip of the needle 90° away from the
bevel using sterile forceps or the needle cap. Mount the needle
on the end of a cotton tip and work with the bevel side away
from the eye. The needle (Figure 3C) or blade (Figure 3D)
should be held tangential to the eye surface. Motions when
performing the procedure

Positioning
Lay the patient in a comfortable supine position, with the
involved eye closest to the attending clinician. Wear
loupes if they are available and illuminate the eye with a
medical
light or, alternatively, use the light and magnification from the
ophthalmoscope held in the non-dominant hand. Unfortunately,
the ophthalmoscope does not facilitate stereopsis. Ask the
patient to focus on a particular point on the ceiling so that the
foreign body sits as centrally between the lids as possible.
Avoiding the lids and lashes is more sterile, and reduces the
chance of eliciting a blink reflex. If necessary, the eyelids can
be kept open using an eyelid speculum, the examiner’s
fingertips, a cotton tip or an assistant.

Figure 3. Rust rings

A. Corneal rust ring; B. Use of moist cotton tip; C. Further removal with 25G
hypodermic needle; D. 15 blade scalpel

© The Royal Australian College of General Practitioners REPRINTED FROM AFP VOL.46, NO.3, MARCH 2017 91
2017
should come from the finer joints of the fingers, with the hand
resting on a firm point of contact.
The aim of the procedure is the safe and complete removal of
the foreign body and any surrounding rust ring (Figure 3A–D).
It is best to accomplish this in one to two sittings in total, so if
there is any doubt this has not been achieved then referral for
slit lamp
examination and complete removal is advised. The site of a
residual rust ring, even at the peripheral cornea, is at risk of
infection and recurrent erosion. The flat part of the 15 blade tip
can be useful to remove the rust ring (Figure 3D). Dental burrs
should be avoided because of the risk of deeper damage to the
corneal stroma and infection from the usual non-sterile status of
the instrument.
Irrigation
Irrigation of the ocular surface and upper and lower fornices
can be performed after the procedure to wash out any residual
loose foreign body material. A 10 mL ampoule of sterile saline
is usually sufficient.
Post-procedure
Antibiotic ointment such as chloramphenicol 0.5% should be
instilled and a double eye pad applied, with the inner one doubled
over in a manner that the eyelid cannot be opened. The patient
needs instruction not to drive or operate machinery while wearing
the eye pad. This must be documented clearly in the patient’s
medical notes. Generally, eye pads are kept on for a period of
24 hours to expedite healing of the epithelial defect and for
pain relief. An alternative approach is to omit the eye pad but
use the antibiotic ointment or drops four times a day. This
depends on the doctor’s and patient’s preference. The literature
strongly suggests that there is no difference in time to healing
or complication rate with or without patching.11,12 Over-the-
counter oral analgesia can be used for pain relief. Do not
discharge the patient with topical anaesthetic drops; these result
in an increased complication rate from corneal anaesthesia.13
Laboratory research also suggests time-dependant and dose-
dependant toxicity.14
The patient can be examined the following day to measure
visual acuity again and repeat fluorescein staining. Any
increase
Box 2. Indications for referral to an ophthalmologist
• Penetrating eye injury or intraocular foreign body
• Incomplete removal or practitioner uncertainty
• Persisting foreign body symptoms
• Persisting rust ring
• Persisting vision loss
• Keratitis
• Endophthalmitis
• Persisting epithelial defect
• Recurrent erosion
• Paediatric or uncooperative patients that may require
examination under anaesthesia
in pain, photophobia, redness, epithelial defect size or
opacity may indicate the onset of keratitis and requires a
referral.
Topical antibiotics in the form of ointment or drops, which
are less blurring, are continued four times a day for five to
seven days. This visit is also an opportune time for patient
education on the importance of wearing eye protection while
undertaking activities that pose risks. A certificate of leave
from work or study for one to two days is not unreasonable.
Paediatrics
Patients younger than 10 years of age are much less likely to
tolerate examination and foreign body removal. Irrigation and
removal with a cotton tip can be attempted after instillation of
topical anaesthetic drops, provided the patient’s head can be
stabilised with safety. If there is any concern, the patient needs
to be referred to a paediatric facility where examination and
treatment under general anaesthesia are possible.
Referral and prognosis
Most corneal foreign bodies result in minimal superficial
scarring of no visual significance. However, removal of a
corneal foreign body without the aid of a slit-lamp can be a
challenging procedure, and if the GP does not feel safe to
proceed, referral to an ophthalmologist is warranted. This
pertains particularly to central and paracentral corneal foreign
bodies that are deeper than expected. Even when removed
with minimal iatrogenic trauma, this location caries a higher
risk of a visually significant corneal scar. Pertinent indications
for referral are summarised in Box 2.
Key points
• Initial assessment and management of corneal foreign bodies is
within the scope of a GP.
• A moistened cotton bud, 25G hypodermic needle or 15 blade is a
suitable approach for superficial foreign bodies and rust rings in
the office provided there is good light, adequate magnification
and a cooperative patient.
• Referral to an ophthalmologist is indicated if there are any
concerns.
Authors
Alison Fraenkel BBiomedSc, MBBS, Preclinical Fellow, City Eye Centre,
Brisbane, Qld
Lawrence R Lee MBBS, FRANZCO, FRACS, Associate Professor, City Eye
Centre, University of Queensland; Royal Brisbane & Womens Hospital, Brisbane,
Qld. eye@cityeye.com.au
Graham A Lee MD, MBBS, FRANZCO, Associate Professor, City Eye Centre,
University of Queensland; Mater Hospital, Brisbane, Qld
Competing interests: None.
Provenance and peer review: Commissioned, externally reviewed.
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 RESEARCH ARTICLE

Impact of pterygium on the ocular surface

and meibomian glands
Ana Claudia Viana Wanzeler 1☯¤*, Italo Antunes Franc¸ a Barbosa1☯¤, Bruna
Duarte1,2☯, Eduardo Buzolin Barbosa1☯, Daniel Almeida Borges1☯, Monica Alves1☯
1 Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas—
UNICAMP, Campinas, SP, Brazil, 2 Pontific Catholic University of Campinas–PUCCAMP,
Campinas, SP, Brazil

☯ These authors contributed equally to this work.

¤ Current Address: Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas
— UNICAMP, Campinas, SP, Brazil.
* anaclaudiavw@yahoo.com.br

Abstract

OPEN ACCESS Competing interests: The authors have declared that no competing interests exist.

Citation: Wanzeler ACV, Barbosa IAF, Duarte

B, Barbosa EB, Borges DA, Alves M (2019)
Impact of pterygium on the ocular surface
and meibomian glands. PLoS ONE 14(9):
e0213956. https://doi.
org/10.1371/journal.pone.0213956

Editor: Deepak Shukla, University of

Illinois at Chicago, UNITED STATES

Received: March 1, 2019

Accepted: August 19, 2019

Published: September 12, 2019

Copyright: © 2019 Wanzeler et al. This is an

open access article distributed under the
terms of the Creative Commons Attribution
License, which permits unrestricted use,
distribution, and reproduction in any medium,
provided the original author and source are
credited.

Data Availability Statement: All relevant data

are within the manuscript and Supporting
Information files.

Funding: Funded by �M.A. Grant

(#2014/19138-5). Fundac¸ão de Amparo a
Pesquisa Estado de São Paulo.
’http://www.fapesp.br/. The funders had no role
in study design, data collection and analysis,
decision to publish, or preparation of the
manuscript. �The other authors received
no specific funding for this work.
Purpose Pterygium greatly impacts on ocular surface by inducing direct alterations in the
To analyze how ocular surface pattern of meibomian glands besides corneal irregularities, conjunctival hyperemia
parameters correlate to and lacrimal film alterations, inducing significant symptoms and potential signs of
presence of pterygium and dysfunction.
investi- gate the possible
impact of pterygia on tear film
findings and meibomian glands
findings.

Methods
We investigated objective
parameters of the ocular surface
such as conjunctival hyperemia,
tear film stability and volume,
meibomian gland dysfunction, dry
eye disease, corneal topog-
raphy comparing healthy
individuals and correlating with
the pterygium clinical
presentation.

Results
A total of 83 patients were
included. Corneal astigmatism
induction was 2.65 ± 2.52 D (0.4–
11.8). The impact of pterygium on
the ocular surface parameters
compared to matched con- trols
was seen in: conjunctival
hyperemia (control
1.55±0.39/pterygium 2.14±0.69; p
= 0.0001), tear meniscus height
(control 0.24±0.05 mm/pterygium
0.36±0.14mm; p 0.0002),
meiboscore lower eyelid (control
0.29±0.64/pterygium 1.38±0.95; p
0.0001) and meiboscore upper
eyelid (control
0.53±0.62/pterygium 0.98±0.75; p
= 0.0083). We found a high
number of pterygium patients
(88%) presented meibomian
gland alterations. Interestingly,
meibo- mian gland loss was
coincident to the localization of
the pterygium in 54% of the upper
and 77% lower lids.

Conclusion
Introduction
Pterygium is a non-neoplastic elastotic degeneration originated in the bulbar conjunctiva that
extends to the corneal surface. It can cause symptoms of discomfort, corneal irregularities, aes-
thetics issues thus compromising visual acuity and patients‘quality of life. [1–3] The prevalence of
pterygium varies worldwide. Global prevalence was estimated in 10.2% to 12%, reaching higher
numbers in tropical regions. Several risk factors have been associated with pterygia, such as
geographical latitude, residence in rural areas, old age, race, sex, sun exposure, chronic irritation
and inflammation. [4,5]
Some studies have pointed to tear film and ocular surface varying changes related to pteryg-
ium, but consistent correlations remain unknown. [6–9] Although numerous theories have been
listed in the pathogenesis of the pterygium (e.g. exposure to ultraviolet radiation, viral infection,
oxidative stress, genetic problems, inflammatory mediators, extracellular matrix modulators) the
mechanism responsible development remains controversial. [10] And a better understanding of the
pathophysiological mechanisms associated with pterygium, the morpho- logical alterations on the
ocular surface and functional impact may contribute to specific approaches and more effective
therapeutic proposals for this common ocular condition.
This study aimed to evaluate how ocular surface parameters correlate with pterygium clini- cal
presentation and its impact on ocular surface structures and homeostasis.

Materials and methods

The present study had a transversal, observational and non-interventional design. It was per- formed
after approval from the local research ethics committee (Research Ethics Committee of the State
University of Campinas—Campus Campinas, CAAE 57716516.1.0000.5404 Nº1757.550) and was
conducted in accordance with the tenets of the Declaration of Helsinki and current legislation on
clinical research. Written informed consent was obtained from all subjects after the explanation of
the procedures and study requirements.
All propaedeutic methods were performed in accordance with specific guidelines and regu-
lations. Data was collected during the ophthalmologic exams and in the inclusion of partici- pants
older than 18 years of age diagnosed with pterygium at the Cornea and External Disease
Ambulatory, Department of Ophthalmology, University of Campinas.
Pterygium patients (n = 52) and healthy volunteers (n = 31) were included. We recorded
personal and family history of pterygium, ocular and systemic comorbidities, ocular or sys- temic
medications, visual acuity as well as a full ophthalmic exam. Ancilliary ocular surface evaluation
consisted of: corneal topography, meibography, meniscometry, non-invasive tear film break-up
time measurement, conjunctival hyperemia quantification using the Oculus Keratograph 5M
(OCULUS Optikgera¨te GmbH, Wetzlar, Germany). All procedures were per- formed by the same
examiner as detailed described:
1. Tear film stability: evaluated the Non-invasive Tear Film Break-up Time (NITBUT) by
Ker- atograph 5M through the evaluation of the point by point Placido concentric circles
image during continuous eye-opening interval. The OCULUS Keratograph 5M device was
used to perform a non-invasive method for observation and detection of the tear film
rupture time–non-invasive tear break-up time (NITBUT). The area of first tear film
rupture and its progression throughout the examination time are measured and recorded
automatically without operator intervention. Avoiding the instillation of fluorescein
eliminates any influ- ence in the tear film content and properties and a misinterpretation of
results. The software analyzes Placido’s projected rings in the tear film, automatically
detecting distortions or dis- continuities in the reflected ring pattern. Results are recorded
over time and space and

2 / 10
 translated into a color-coded map. When the corneal image is aligned the following mes- sage
appears: [Please blink 2 times] and measurement are taken automatically. "Break (first)" gives
the moment when the first break is detected on any surface segment. Break (Mean) gives the
mean breaking time for all surface segments where the rupture occurred.
2. Tear meniscus height measured in millimeters in images taken by Keratograph
5M equipment.
3. Meibomian Gland Function: non-contact infrared meibography was performed in the
lower and upper lid using Keratograph 5M. Gland dropout was assessed using meiboscan
infrared device according to the instructions. Meiboscore was used for assessment of the
meibography in the evaluation of the infrared captured images of the meibomian glands.
The classification scale, adapted from Arita et al., used the following degrees for each
eyelid: 0 (no loss of meibomian glands); 1 (loss of the meibomian gland involving less
than one- third of the total meibomian gland area); 2 (loss between one third and two
thirds of the total area of the meibomian gland); and 3 (loss more than two-thirds of the
total meibomian gland area). [11]
4. Pterygium evaluation: pterygium patients were classified according their graduation:
grade 1 to 4 according to fibrovascular tissue extension towards the cornea (grade 1 when
the lesion reaches the limbus, grade 2 when it covers the cornea at about 2 mm, grade 3
when it reaches the pupil margin and grade 4 when it exceeds the pupil). Indeed,
biomicroscopic aspect was noted as involutive atrophic or fleshy (involutive allows the
visualization of structures immediately below and fleshy when fibrovascular tissue
prevents proper visuali- zation of underneath structures). [12] Hence, corneal topography
images were taken for keratometries and astigmatism measurements.
Exploratory data analysis was performed through summary measures (mean, standard
deviation, minimum, median, maximum, frequency and percentage). Comparison between groups
was performed using the Wilcoxon test. The correlation between numerical variables was assessed
using the Spearman coefficient. The level of significance was 5%. The analyses were performed
using the computer program The SAS System for Windows (Statistical Analy- sis System),
version 9.4. (SAS Institute Inc, Cary, NC, USA).

Results
A total of 83 patients were included in this study (52 pterygium patients and 31 healthy volun-
teers). Mean age of 53.69 ± 11.29 (26–75) years old in pterygium groups and 57.32 ± 7.30 (39–
72) in healthy participants (p = 0.6084).
Pterygia classification regarding tissue progression from limbus to the visual axis was: 1.9%
as grade 1; 59.5% grade 2; 32.7% grade 3; and 5.8% as grade 4 (tissue over visual axis). In addi-
tion, 15.4% were atrophic and 84.6% had a fleshy/active clinical appearance. Corneal astigma-
tism induction was 2.65 ± 2.52 D (0.4–11.8). Table 1 shows ocular surface parameters in
pterygium patients and controls and Table 2 shows data distribution according to the pteryg- ium
grades and appearance (Table 3).
Compared to control participants, pterygium patients presented significant alterations regarding
hyperemia (control 1.55±0.39–95% CI 0.02–0.34; pterygium 2.14±0.69–95% CI 1.95–
2.36; p 0.0001), tear meniscus height (control 0.24±0.05 mm- 95% CI 0.22–0.26; pterygium 0.36
±0.14mm—95% CI 0.32–0.40; p 0.0002) and meiboscore lower eyelid (control 0.29±0.64–95%
CI 0.05–0.52; pterygium 1.38±0.95–95% CI 0.77–1.19; p 0.0001) and meiboscore upper eyelid
(control 0.53±0.62–95% IC 0.29–0.76; pterygium 0.98±0.75–95% IC 0.77–1.19; p 0.0083).
Table 1. Comparisons of ocular Surface parameters in pterygium and healthy participants.
Control Pterygiu
m
Mean ± SD 95% CI Mean ± SD 95% CI P value
Age 57.32±7.30 5.76–14.43 53.69±11.2 50.55– 0.6084
(years) 9 56.84
Visual Acuity 0.85±0.21 0.77–0.94 0.63±0.31 0.54–0.71 0.0001�
Tear meniscus height 0.24±0.05 0.22–0.26 0.36±0.14 0.32–0.40 0.0001�
NITBUT first Breakup 10.6±6.51 8.22–13.01 10.64±5.29 9.16–12.11 0.8728
NITBUT average Breakup 14.28±6.06 11.88–16.68 13.55±5.55 12.01– 0.6605
15.10
Conjunctival hyperemia 1.55±0.39 0.02–0.34 2.14±0.69 1.95–2.36 0.0001�
Meiboscore lower 0.29±0.64 0.05–0.52 1.38±0.95 0.77–1.19 0.0001�
Meiboscore upper 0.53±0.62 0.29–0.76 0.98±0.75 0.77–1.19 0.0083�
https://doi.org/10.1371/journal.pone.0213956.t001

We found that 88% of patients presented abnormalities on meibomian glands. Interest- ingly, in
54% of the upper eyelids and 77% of the lower eyelids, the meibomian gland loss appeared nasally
in the same localization of the pterygium. Fig 1 shows the distribution of the meibomian gland
involvement in the upper and lower eyelid and Fig 2 exemplifies the meibo- graphy alterations in
pterygium patients. Indeed, correlation analysis according to both pte- rygium classifications were
performed and corroborated to these findings. Regarding to the extension over the limbus in grades
1–4 meiboscore, significant correlations to the localization of the pterygium in both eyelid were
demonstrated and when evaluating by clinical appearance atrophic pterygium meiboscore superior
correlated with inferior compromise and in fleshy ones, both meiboscores correlated with the
pterygium localization, as shown in Tables 4 and 5.
Regarding the subjective symptoms, the patients’ complaints were evaluated as parameters
such as tearing, ocular discomfort, aesthetics and blurred vision. Such symptoms are closely
related to the tear film and ocular surface abnormalities described.

Discussion
The present study shows that pterygium has a great impact on the parameters and structures of the
ocular surface. It can induce corneal astigmatism, conjunctival hyperemia, tear film abnormalities
and significant structural alterations in the meibomian glands.

Table 2. Data distribution according to pterygium extension over the limbus (grades 1–4).
Grades 1– Grades 3–
2 4
Mean ± SD 95% CI Mean ± SD 95% CI P value
Age (years) 51.5 ± 11.3 47.3–55.6 57.1 ± 10.9 52–62.2 0.09
K1 43.2 ± 2 42.5–44 42.8 ± 3.8 40.7–45 0.92
K2 44.9 ± 1.9 44.1–45.6 47.5 ± 3.2 45.7–49.3 0.001�
Corneal astigmatism 1.6 ± 1.1 1.1–2 4.6 ± 3.3 2.7–6.4 0.006�
(pterygium)
NITBUT 9.8 ± 4.8 8.1–11.6 9.9 ± 5.1 7.6–12.3 0.95
Conjunctival hyperemia 2.7 ± 0.6 2.4–2.9 2.7 ± 0.6 2.4–3 0.96
Tear meniscus height 0.3 ± 0.1 0.3–0.4 0.3 ± 0.1 0.2–0.4 0.27
Red eye (0–10) 7.7 ± 3 6.3–9.1 8 ± 2.1 6.7–9.4 0.96
Irritation (0–10) 7.1 ± 1.7 6.3–7.9 6.5 ± 3.4 4.3–8.6 0.92
Tearing (0–10) 5.8 ± 3.6 4.1–7.4 6 ± 3.9 3.4–8.5 0.76
Blurred vision (0–10) 6.7 ± 3.5 5.1–8.3 7.2 ± 2.9 5.4–9 0.95
Aesthetics (0–10) 7.9 ± 3 6.5–9.3 7.5 ± 3.2 5.4–9.5 0.66
https://doi.org/10.1371/journal.pone.0213956.t002
Table 3. Data distribution according to the pterygium clinical presentation (atrophic and fleshy).
Atrophic Fleshy
Mean ± SD 95% CI Mean ± SD 95% CI P value
Age (years) 58.5 ± 13.3 47.3–69.6 52.8 ± 10.8 49.5–56.1 0.26
K1 42.7 ± 3.3 40–45.5 43.2 ± 2.5 42.3–44 0.40
K2 46.2 ± 5.2 41.8–50.6 45.7 ± 1.8 45–46.2 0.40
Corneal astigmatism 3.5 ± 2.7 1.1–5.8 2.4 ± 2.4 1.6–3.2 0.18
(pterygium)
NITBUT 9.5 ± 7.1 3.5–15 10 ± 4.5 8.7–11.5 0.36
Conjunctival hyperemia 2.3 ± 0.1 2.5–2.9 2.7 ± 0.7 1.8–2.9 0.005�
Tear meniscus height 0.4 ± 0.2 0.2–0.6 0.3 ± 0.1 0.31–0.39 0.25
Red eye (0–10) 9±1 7.7–10 7.7 ± 2.8 6.6–8.8 0.82
Irritation (0–10) 7±2 4.5–9.4 6.8 ± 2.5 5.9–7.8 0.51
Tearing (0–10) 6.4 ± 2.6 3–9.6 5.8 ± 3.8 4.4–7.3 0.92
Blurred vision (0–10) 8.8 ± 1 7.4–10 6.7 ± 3.4 5.4–7 0.25
Aesthetics (0–10) 7 ± 2.9 3.3–10.6 8±3 6.8–9 0.34
https://doi.org/10.1371/journal.pone.0213956.t003

Ocular hyperemia can be considered as a clinical sign of inflammation that may suggest severity
and progression of a specific disease. [13] High rates of hyperemia were observed in the eyes with
pterygium, which may be explained by the number of fleshy pterygia present in this study and by
the richer vascularization of the pterygium itself, even in the atrophic ones. The advantage of using
the image analysis method is that one can eliminate individual variabil- ity and the bias of
subjective classification. [14]
Although pterygium symptoms resemble dry eye and others ocular surface diseases symp- toms,
such as dryness and irritation, no decrease on non-invasive tear break-up time (NIT- BUT) was
observed in this cohort. A study carried out in 2014 had already shown that the size of the
pterygium does not correlate with the tear break-up time and the results of the Schir- mer‘s test.
[15] Another study comparing Schirmer’s test results and tear break-up time before and after
pterygium surgery showed that, even with the removal of the pterygium, there were no changes in
those tests results one month after surgery. [16] On the other hand, Ozsutcu
et al. found lower values of tear film test and Schirmer I test in eyes with pterygium when com-
pared to healthy eyes, which can be explained by the significantly higher tear osmolarity levels

Fig 1. Meiboscore classification in control individuals (blue: lower eyelid; green: upper eyelid) and pterygium patients
(yellow: lower eyelid; red: upper eyelid).
https://doi.org/10.1371/journal.pone.0213956.g001
 Fig 2. Examples of meibography alterations in pterygium patients where gland dropout (yellow arrow) occurred along
with the topography of the fibrovascular tissue (red arrow) upper eyelid (grade 2; grade 2; grade 1) and lower eyelid
(grade 1; grade 2; grade 2) respectively.
https://doi.org/10.1371/journal.pone.0213956.g002

found in the study.[6] In our study pterygium patients had statistically higher tear meniscus height
and no differences in NITBUT, which may be pointed as a picture of the ocular surface
compensatory mechanisms. Higher measurements of tear meniscus may be related to chronic
ocular inflammation and friction and abnormal distribution of tear film leading to surface dis-
turbances in tear flow dynamics and reflex tearing, as described in previous studies.[16] Although,
normal tear function and no alteration on tear meniscus height has been already described in the
pterygium patients [14,17]
Pterygium can induce corneal aberrations that compromise patients’ visual acuity. Studies
indicate the length of the pterygium and vascularization as predictive factors for increased induction
of astigmatism.[17–19] On the other hand, pterygium excision leads to a decrease in acquired
astigmatism to acceptable levels, as shown by studies that evaluated the impact of sur- gery on
corneal astigmatism reduction.[20] Regarding the surgical procedure, there was no significant effect
on the degree of astigmatism were found comparing different surgical tech- niques.[21]

Table 4. Correlations between meibomian gland dysfunction and ocular surface parameters according to pterygium grades (1–4).
Grade 1–2 Grade 3–
4
Meiboscore Meiboscore Meiboscore Meiboscore
superior inferior superior inferior
K1 0.037 0.287 0.444 0.426
K2 0.212 0.093 0.580� 0.262
CA 0.309 -0.226 -0.198 -0.402
NITBUT 0.151 0.050 0.085 -0.425
TMH 0.213 0.226 0.090 0.213
CH -0.042 0.190 0.154 0.293
Meiboscore superior 0.277 0.483�
MGD/PTCOL 0.578 � 0.069 0.580 � 0.424
superior
Meiboscore inferior 0.277 0.483�
MGD/PTCOL inferior 0.147 0.557 �
0.521� 0.768�

Correlations coefficient value by Spearman analysis of Meibomian Gland Dysfunction and Pterygium extension over the limbus (grades 1–4).
�
P < 0.05. MG: Meibomian Gland; K: keratometry; CA: corneal Astigmatism; NITBUT: Non-Invasive Tear Breakup Time; TMH: Tear Meniscus Height; CH:
Conjunctival Hyperemia; MGD/PTCOL: MG drop dropout area/pterygium colocalization

https://doi.org/10.1371/journal.pone.0213956.t004
Table 5. Correlations between meibomian gland dysfunction and ocular surface parameters according to pterygium clinical appearance (atrophic and fleshy).
Atrophic Fleshy
Meiboscore Meiboscore Meiboscore Meiboscore
superior inferior superior inferior
K1 0.326 0.377 0.149 0.403
K2 -0.078 0.025 0.184 -0.011
CA -0.223 -0.107 0.181 -0.415�
NITBUT 0.299 -0.264 <0.000 -0.204
1
TMH 0.534 0.088 0.127 0.269
CH 0.143 0.529 -0.022 0.186
Meiboscore superior 0.800 0.277
MGD/PTCOL 0.276 0.266 0.590� 0.202
superior
Meiboscore inferior 0.800� 0.277
MGD/PTCOL inferior 0.690 0.800 0.234 0.616�

Correlations coefficient value by Spearman analysis of Meibomian Gland Dysfunction and Pterygium clinical appearance (atrophic/fleshy).
�
P < 0.05. MG: Meibomian Gland; K: keratometry; CA: corneal Astigmatism; NITBUT: Non-Invasive Tear Breakup Time; TMH: Tear Meniscus Height; CH:
Conjunctival Hyperemia; MGD/PTCOL: MG drop dropout area/pterygium colocalization

https://doi.org/10.1371/journal.pone.0213956.t005

Meibomian gland dysfunction (MGD) is a chronic and diffuse disorder occurs in meibo- mian
glands. The etiology of MGD includes primary causes which are not fully understood, and
secondary causes including ocular disorders such as blepharitis, conjunctivitis, etc., and systemic
disease such as lupus erythematosus, Sjogren syndrome. [22] MGD was found in a significant
number of pterygium patients. Interestingly, areas of meibomian gland loss coinci- dently
appeared in the nasal topographic localization of the pterygium, both in the upper and lower
eyelids. Wu et al described recently, a similar association of pterygium and MGD. This study
reported NIBUT, meibomian gland dropout and meibum score alterations in pterygium patients.[9]
However, besides these findings, by evaluating each patient meibography picture, an association
of the dropout area related to the topography of the pterygium was observed in a considered
number of cases, to our knowledge, no association with pterygium localization was described
before. [23]
The ocular surface homeostasis is crucial to guarantee comfort, quality of vision and proper
maintenance of all structures that compose this functional unit. Such peculiar relationship can be
profoundly changed by the loss of regularity promoted by the pterygium growth, as well as
changes meibomian gland and tear film changes described herein. However, a deep under-
standing of the underlying pathophysiological mechanisms related to those MGD and tear film
alterations still requires further investigation. We can hypothesized that those changes might be
related to local inflammatory conditions and the release of inflammatory cytokines that can spread
to the anterior and posterior margin of the eyelid, resulting in meibomian gland alterations, as seen
in other ocular surface disorders.[23] It was suggest direct inflamma- tory damage to eyelid due to
elevated inflammatory status and the release of inflammatory cytokines, including tumor necrosis
factor-α, interleukin-4, and interleukin-5, may spread to the anterior and posterior lid margin, thus
resulting in meibomian gland changes.[24] Indeed, chronic repeated inflammation might also
cause meibum stagnation followed by the keratini- zation of orifices in the meibomian glands.
[23] Another mechanism can be attributed to mechanic trauma, due to an effect of the direct
friction caused by the pterygium in the tarsal conjunctiva may play a contributory role. Similar
trauma condition have been studied in con- tact lens users, associated with adverse changes in
meibomian gland morphology and in the
 condition of the lid margin and meibum, suggesting that contact lenses negatively affect mei-
bomian glands.[25]
However, this finding demands further exploration. Of note, meibomian gland proper pro-
duction and delivery is crucial to tear film stability and evaporative dry eye is considered the most
common subtype of disease affection a great number of individuals worldwide. Thus, dis- ruption of
meibomian gland function negatively impacts both the quality and quantity of mei- bum and in turn
affects ocular surface health. Increased tear evaporation, tear film instability and consequent
hyperosmolarity, inflammation and ocular surface damage lead to ocular dis- comfort and visual
disruption. The findings related to pterygium and meibomian gland described in this study, may
indicate a need of closer attention regarding to quantification of related symptoms, search of clinical
signs and overall preventive measurements to guarantee meibomian gland functional support, such
as eyelid hygiene, mechanical expression and other procedures.
Some limitations of this study must be pointed out. Our sample consisted of patients that
consecutively presented for consultation. Although with distinct grades according to the pro-
posed classification system, the included participants had primary, nasal pterygia. Recurrent and
temporally located pterygia may carry different features, not evaluated in this study. The use of
noninvasive technology for ocular surface study has proved to be of great value, but a broad
investigation of tear and tissue inflammatory mediators may enhance the understanding of
pterygium mechanisms and the ocular surface changes described herein.
This study demonstrated a detailed evaluation of the clinical parameters of the ocular sur- face in
the pterygium population and quantified the symptoms. Therefore, our results not only allowed for a
contribution to the understanding of the disease but also created new perspec- tives for future
studies.

Conclusion
The present study shows that pterygium impacts on ocular surface parameters, especially by
inducing direct alterations in the pattern of meibomian glands and tear film.

Supporting information
S1 Data. wanzeler.dataset.
(XLSX)

Author Contributions
Conceptualization: Ana Claudia Viana Wanzeler, Italo Antunes Franc¸a Barbosa, Bruna Duarte,
Monica Alves.
Data curation: Ana Claudia Viana Wanzeler, Italo Antunes Franc¸a Barbosa, Bruna Duarte,
Eduardo Buzolin Barbosa.
Formal analysis: Ana Claudia Viana Wanzeler, Italo Antunes Franc¸a Barbosa, Eduardo Buzo- lin
Barbosa, Daniel Almeida Borges.
Funding acquisition: Monica Alves.
Investigation: Ana Claudia Viana Wanzeler, Italo Antunes Franc¸a Barbosa, Eduardo Buzolin
Barbosa.
Methodology: Ana Claudia Viana Wanzeler, Italo Antunes Franc¸a Barbosa.
Project administration: Monica Alves.
 Resources: Italo Antunes Franc¸a Barbosa, Bruna Duarte.
Supervision: Monica Alves.
Validation: Daniel Almeida Borges.
Visualization: Daniel Almeida
Borges.
Writing – original draft: Ana Claudia Viana Wanzeler.
Writing – review & editing: Italo Antunes Franc¸a Barbosa, Bruna Duarte, Eduardo
Buzolin Barbosa, Daniel Almeida Borges, Monica Alves.

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 ARCH soc E sP OFTALMOL . 2 0 1 6;9 1(3):134–137

ARCHIVOS DE LA
SOCIEDAD ESPAÑOLA DE
OFTALMOLOGÍA

Short communication

Foreign body embedded in the iris after cataract surgery 6

E. Santos-Bueso ∗, M. Jiménez-Santos, D. Díaz-Valle, J.A. Gegúndez-Fernández,
R. Cuin˜ a-Sardin˜ a, J.M. Benítez-del-Castillo, J. García-Sánchez
UNIDAD de NeurOOFTALMOLOGÍA, Servicio de OFTALMOLOGÍA, HOSPITAL Clínico SAN CARLOS, MADRID, SPAIN

A R T I C L E I N F O A B s T R A C T

Article history:
CASE report: A 75-year-old woman who had had cataract surgery in her left eye and showed a visual acuity
Received 29 November 2014
of 0.8 twenty-four hours post-surgery. Biomicroscopy revealed a foreign body attached to the iris in the nasal
Accepted 3 November 2015
sector that coincided with the main incision of the pha- coemulsification, which was then removed in a
Available online 28 February 2016
second surgical procedure. It was analyzed and described as an inert structure made of plastic.
Discussion: The possible origin of the presence of a fragment of plastic in the postoperative period
Keywords: Foreign following cataract surgery is established. In this case, its inert nature did not cause any further intraocular
body Iris inflammation. Its rigid structure also favored its attachment to the iris, thus avoiding any other complications.
Cataract surgery There must be greater preventative measures during cataract surgery, including checking the instruments and
Phacoemulsification accessories before and after the surgical procedure.
Plastic © 2015 Sociedad Espan˜ ola de Oftalmología. Published by Elsevier España, S.L.U. All rights
reserved.

Cuerpo extran˜ o enclavado en iris después de cirugía de catarata

R E s U M E N
PALABRas CLAve: Cuerpo
CASO clínico: Mujer de 75 an˜ os intervenida de catarata en ojo izquierdo, que presentaba a las 24 h una agudeza
extran˜ o Iris
visual de 0,8. En la biomicroscopia destacaba un cuerpo extran˜ o anclado al iris en sector nasal coincidente
Cirugía de catarata
con la incisión principal de la facoemulsificación, que fue retirado en un segundo acto quirúrgico. Fue
Facoemulsificación
analizado e informado como estructura inerte de naturaleza plástica.
Plástico

6
Please cite this article as: Santos-Bueso E, Jiménez-Santos M, Díaz-Valle D, Gegúndez-Fernández JA, Cuin˜ a-Sardin˜ a R, Benítez-del- Castillo JM, et al. Cuerpo
extran˜ o enclavado en iris después de cirugía de catarata. Arch Soc Esp Oftalmol. 2016;91:134–137.
∗
Corresponding AUTHOR.
E-mail address: esbueso@hotmail.com (E. Santos-Bueso).
2173-5794/© 2015 Sociedad Espan˜ ola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
 ARCH soc EsP OFTALMOL . 2 0 1 6;9 1(3):134–137 135

Discusión: Planteamos el posible origen de la presencia del resto plástico en el postopera- torio de
la cirugía de la catarata. En este caso su naturaleza inerte no desencadenó mayor inflamación
intraocular. Además, la estructura rígida favoreció su anclaje al iris evitando otras complicaciones.
Deben extremarse las medidas preventivas en la cirugía de la catarata revisando incluso los
instrumentos y accesorios al terminar la cirugía.
© 2015 Sociedad Espan˜ ola de Oftalmología. Publicado por Elsevier España, S.L.U. Todos
los derechos reservados.

Introduction

The presence of foreign bodies (FB) in the anterior

chamber (AC) after cataract surgery is an infrequent
finding, although it must be taken into account even
when the surgery was ade- quately carried out. The
nature of said foreign bodies can be diverse, although the
most frequent ones are cataract nuclear fragments (NF)
that remain retained and hidden 1,2 behind the iris, in
iridian crypts or the iridocorneal angle. In these cases,
corneal and macular edema can occur in the immediate
postop or even several years later, making diagnosis
difficult due to not relating clinic with the surgery when
the NF are not visible.1,2
In addition, metal remains of the surgical material
have been described,3 intraocular lens haptics4,5 and even Fig. 2 – Foreign body detail.
cotton fibers.6 The present report describes the presence
of a plas- tic anchored to the iris in the immediate
cataract surgery postop in a 75-year-old patient, and
discusses the possible origin thereof.

Clinic case report

inflammation in the AC. Intraocular pressure (IOP) was
Female, 75, who underwent cataract operation in the left
eye with phacoemulsification and intra-ocular lens
implant, who exhibited 24 h later a visual acuity of 0.8.
Biomicroscopy showed a shiny FB (Figs. 1 and 2) in the
nasal iridian sector, matching the main
phacoemulsification incision. In addi- tion, the patient
exhibited slight corneal edema and slight

Fig. 1 – Foreign body in anterior chamber, 24 h after

cataract surgery.

of 16 mmHg while ocular fundus (OF) was normal. AC

optic coherence tomography was taken with Cirrus® HD-
OCT (Carl Zeiss Meditec, Dublin, California, USA)
which showed the FB anchored to the iris and projected
toward the AC (Figs. 3). The patient was intervened with
the Stellaris® phacoemulsifica- tor (Baush + Lomb,
Aliso Viejo, California, USA) applying the
microincision technique.
Twenty-four hours later, the patient was intervened
again to extract the FB, which required active traction
with forceps as its anchoring to the iris was confirmed.
The FB was sent to the pathological anatomy
department for analysis and reported as inert plastic
structure, suggesting possible origin in the han- dle of
the phacoemulsificator tip. One week later, the patient
exhibited VA of 0.8, with slight residual corneal edema
and slight AC inflammation. IOP was of 14 mmHg and
OF was nor- mal, without macular edema. At month 1
and 3 the patient was asymptomatic, with VA of 0.9 and
rest of examination normal, upon which she was given
hospital release.

Discussion

The presence of FBs in cataract surgery postop is

infrequent but it can give rise to ocular complications
with loss of secondary vision. In turn, NFs can produce
corneal edema, intraocular inflammation or even
macular edema in the
136 ARCH soc EsP OFTALMOL . 2 0 1 6;9 1(3):134–137

High Definition Images: Anterior Segment 5 Line OD OS

Raster
Scan Angle: Spacing: 0.25 Length: 3 mm
0º mm

Fig. 3 – Cirrus® HD-OCT (Carl Zeiss Meditec, Dublin, California, USA) optic coherence tomography of the foreign
body fixed to the iris.

immediate postop or during a period of time that can
extend several years after surgery.
Even though the most frequent FBs are retained NFs,
a range of FBs of different nature can be encountered.
Varma et al.3 described a piece of metal that detached
from the tip of the chopper and anchored in the ciliary
angle, which later mobilized and was removed with
Micro Forceps and gonioscopy. Gokhale4 described
corneal edema secondary to a detached intraocular lens
haptic which was retained and subsequently moved
toward the corneal endothelium. Solano et al.5 described
2 cases of nontraumatic deinsertion of the intraocular
lens haptics of 3 pieces, 16 and 20 years respec- tively after
cataract surgery. The presence of cotton fibers in the AC
was observed by Shimada et al.6 in 1.7% of inter- vened
patients, a percentage which increased to 6.4% during
surgery. However, said cotton fibers did not produce
inflam- mation within a follow-up of one year. Similarly,
Bakbak et al.7 considered that retained fibers did not
cause additional
short-term inflammation and were well tolerated, in
contrast with other retained FBs.
The case presented herein is infrequent and has not
yet been described. The form and nature of the FB
indicate that it could originate from 2 possible sources.
On the one hand, it could have detached from the
plastic cover of the phacoemul- sificator handpiece.
This cover may have not been placed and adjusted
adequately and, when the phacoemulsification pro-
cess was activated, the tip of the piece could have
destroyed the plastic, observing in the elevated
structure the overlap- ping and parallel fragmentation
lines produced by ultrasound (Fig. 2). The plastic went
unnoticed during the surgery and it affixed to the iris,
which avoided its displacement toward the
iridocorneal angle of the corneal endothelium. At the
end of the surgery, said phacoemulsificator handpiece
plastic cover fragment went unnoticed.
Another hypothesis is that the plastic could have
detached from the thread used to adjust the
phacoemulsificator tip
 ARCH soc EsP OFTALMOL . 2 0 1 6;9 1(3):134–137 137

during calibration. In this case it must have remained

hid-
REFERENCE s
den throughout the surgery, which is unlikely because these
remains are generally visible in different stages of the surgery,
above all during irrigation and final aspiration. It could have remained hidden behind the iris, subsequently moving and
attaching itself to the iris after surgery.
At any rate and regardless of the origin of the FB, its inert and plastic nature did not produce any inflammation apart
from that of the surgery. Even so, it was decided to remove it due to the apparent risk of displacement causing compli-
cations in the future. The approach toward FBs should be individual on the basis of the characteristics of each FB and
patient. If access is difficult and the FB remains stable, a conservative approach can be adopted, with regular patient
examinations. However, the potential long-term instability of all FBs makes their extraction recommendable.
As conclusion, preventive measures in cataract surgery must be extreme, checking the instruments at the end of the
surgery as well as the integrity of all accessories. These meas- ures should also be applied in all surgeries, even those
with apparent evidence of success.

Conflict of interest

No conflict of interests was declared by the authors.

1. Asensio-Sánchez VM, Ajamil S, Ramoa-Osorio R,
Trujillo-Guzmán L. Sudden macular edema 2 years after cataract surgery due to retained nuclear fragment. Arch Soc Esp Oftalmol. 2014;89:272–4.
2. Pandit RT, Cobum AG. Sudden corneal edema due to retained lens nuclear fragment presenting 8.5 years after cataract surgery. J Cataract Refract Surg.
2011;37:1165–7.
3. Varma DK, Shaikh VM, Hillson TR, Ahmed II. Migration of retained chopper tip after phacoemulsification. J Cataract Refract Surg. 2010;36:857–
60.
4. Gokhale NS. Late corneal edema due to retained foldable lens fragment. Indian J Ophthalmol. 2009;57:230–1.
5. Solano JM, Baratz KH, Mahr MA, Erice JC. Late spontaneous haptic disinsertion from a three-piece intraocular lens. Am J Ophthamol. 2007;143:521–
2.
6. Shimada H, Arai S, Kawamata T, Nakashizuka H, Hattori T, Yuzawa M. Frequency, source, and prevention of cotton fibers in the anterior chamber
during cataract surgery. J Cataract Refract Surg. 2008;34:1389–92.
7. Bakbak B, Gedik S, Ozturk BT, Koktekir BE, Gonul S, Yilmaz M. Quantitative assessment of anterior chamber inflammation in patients with retained
presumed intraocular cotton fiber
after phacoemulsification. Ocul Immunol Inflamm. 2013;21: 207–11.

Lkjopkjopkokoko[pk
 Hindawi
Journal of Ophthalmology
Volume 2018, Article ID 2474173, 5 pages
https://doi.org/10.1155/2018/2474173

Research Article
Corneal Epithelial Damage and Impaired Tear Functions in
Patients with Inflamed Pinguecula

Erkut Ku¨çu¨k ,1 Ug˘ur Yılmaz,2 and Ku¨rsad Ramazan Zor1

Ophthalmology Department, Nig˘de O¨ mer Halisdemir University, Faculty of Medicine, 51240 Nig˘de, Turkey
1
2
Ophthalmology Department, Pamukkale University Faculty of Medicine, 20160 Denizli, Turkey

Correspondence should be addressed to Erkut Ku¨çu¨k; erkutkucuk@yahoo.com

Received 30 July 2018; Revised 27 September 2018; Accepted 9 October 2018; Published 31 October 2018

Academic Editor: Jesu´s Pintor

Copyright © 2018 Erkut Ku¨çu¨k et al. This is an open access article distributed under the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the
original work is properly cited.
Purpose. In this study, we evaluated corneal epithelial integrity and tear film parameters in patients with
inflamed pinguecula and compared these findings with their fellow eyes and with healthy controls. Methods.
We evaluated the fluorescein staining properties and performed the tear break-up time (TBUT) test and
Schirmer 2 test (ST2) measurements of 32 patients who had symptomatic unilateral inflamed pinguecula and
compared the results with their fellow eyes and also with an age- and sex-matched control group. Results.
Twenty-three eyes (72%) in the inflamed pinguecula group and 1 eye (3.1%) in the fellow eyes group had
punctate epithelial staining (PES) or epithelial defect on the nasal cornea (p < 0.001). There was no PES or
�
epithelial defect in the control group. Eyes with inflamed pinguecula (n 32) had lower TBUT and ST2 values
�
compared to the control group (n 32) (p < 0.001 for both). Fellow eyes (n 32) also had lower TBUT and ST2
values compared to the control group (p 0.003 for both). There was no difference in the TBUT� and ST2 results
between the eyes with inflamed pinguecula and fellow eyes (p 0.286 and p 0.951, respectively). Conclusion. A
high percentage of eyes with inflamed pinguecula had nasal corneal epithelial staining or epithelial defect. We
also found lower TBUT and ST2 results in eyes with inflamed pinguecula and the fellow eyes compared to the
control group. These findings may be important in pathogenesis of pinguecula and pterygium and also in
uncovering their relation.

1. Introduction Pterygium is a triangular growth of conjunctival fibro-

vascular tissue onto the cornea, usually located at the nasal
Pinguecula is a yellowish elevated mass commonly
located on the nasal bulbar conjunctiva close to the
limbus [1]. Its prevalence increases with age, and
ultraviolet radiation (UVR) is a risk factor in its
pathogenesis [2, 3]. Male gender and diabetes mellitus
are also reported risk factors [4]. Histological studies
reported abnormal differentiation and squamous
metaplasia of the conjunctival epithelium, ex-
aggeration and distortion in the production of elastic
fibers, and abnormality of their organization in the
subepithelial connective tissue [5–7]. It was reported
that 22.5% to 70.1% of the population has pinguecula
[4, 8]. This heterogeneity in the prevalence may be due
to differences in age, geo- graphic location, and
ethnicity of participants. Pinguecula may be inflamed,
causing hyperemia, pain, and foreign body sensation.
cornea. Its prevalence is lower than that of pinguecula.
It can cause decreased visual acuity, irritation, and pain
due to inflammation and cosmetic problems. Although
surgery is effective in its treatment, the risk of
recurrence is still an important problem. Ultraviolet
radiation (UVR) is thought to be a factor in the
development of both pinguecula and pterygium. It is
hypothesized that UVR causes conjunctival
degeneration and the formation of pinguecula. With in-
creased exposure, corneal epithelial and stem cells may
be affected and lead to the formation of pterygium [9,
10]. But it is still unknown if pinguecula is a precursor
of pterygium or if so, what causes its progress to
pterygium.
Several studies reported abnormalities of tear
function tests in pinguecula patients [2, 11]. The
abnormality of the tear film and mechanical trauma
may cause inflammation of pinguecula [12]. Inflamed
pinguecula has attracted little attention in the
ophthalmic community. In this study, we investigated
the fluorescein staining properties and tear film
 Journal of
Ophthalmology
discussed the role of these parameters in the possible
evo- lution of the inflamed pinguecula to pterygium.
2. Materials and Methods
This controlled multicenter study was performed in the
Ophthalmology Department of Nig˘de O¨ mer
Halisdemir
University (Nig˘de, Turkey) and Ophthalmology
Department of Pamukkale University Hospital (Denizli,
Turkey). Both cities are located at the same latitude
(38°), and they have the same distance from the equator.
Denizli is located approxi- mately 124 km from the
Aegean Sea, and Nig˘de is located 130 km from the
Mediterranean Sea. Although regional differences can
exist, these two cities show similar climatic
characteristics. Thirty-two consecutive patients who
applied to these clinics between July 2017 and
September 2017 and had symptomatic unilateral
inflamed pinguecula were in- cluded. Twelve of these
patients were from Pamukkale
University Hospital and 20 from Nig˘de O¨ mer
Halisdemir
University Ophthalmology Department. Symptomatic
inflamed pinguecula was described as a combination of
vascular congestion and hyperemia of the pinguecula
and adjacent conjunctiva in biomicroscopic examination
together with patients’ description of a recent increase in
ocular redness and one or more of the following
symptoms: pho- tophobia, pain, foreign-body sensation,
discomfort, and tearing. Two independent experienced
ophthalmologists (EK and UY) diagnosed the patients
for inclusion criteria. A control group (n 32) was
formed from age-matched in- dividuals that did not
�
have any ophthalmic disease other than refractive
problems. Subjects who had corneal pathologies,
allergic conditions, previous corneal and/or conjunctival
surgery, meibomian gland dysfunction, active ocular in-
fection, and contact lens users were excluded. All
participants underwent complete ophthalmologic
examination. To ensure reproductivity, all patients
diagnosed with inflamed pin- guecula were reexamined,
and tests of the tear function were performed on the
following day in the morning in the ophthalmologists’
dimly lit examination room. Corneal staining properties
were evaluated using fluorescein sodium solution 2%
(Fluorescite ; Alcon Laboratories, Inc., Fort Worth,
Texas 76134, USA). For TBUT test measurements, a
®
drop of 2% fluorescein solution was applied to the
lateral inferior fornix. The patient was asked to blink
several times for uniform distribution of fluorescein and
then instructed to look ahead without blinking. The time
from the last blink to the appearance of the first dry spot
on the cornea was recorded using the cobalt blue filter
of the biomicroscope and a stopwatch. Three
consecutive measurements were made, and the mean of
measurements was recorded. Thirty minutes later, in the
dimly lit examining room, a topical anesthetic agent
proparacaine hydrochloride 0.5% drop (Alcaine ; Alcon,
Fort Worth, TX) was applied to the inferior fornix, and
three minutes later, a standard Schirmer test filter strip
(Bio Schirmer ; Bio-Tech Vision Care, Ahmedabad, ® be an im- portant factor [2, 3]. Fluorescein is a
Gujarat, India) was inserted into the lateral inferior
fornix at the junction of the middle and lateral thirds of
®
the lower eyelid, taking care not to touch cornea. The
patient was asked to keep eyes open and blink as
necessary. After five minutes, the filter
2
strip was removed and wetting was recorded. This study
was performed according to the tenets of Declaration of
Helsinki, and the study received approval from
Pamukkale University Ethics Committee. Written
informed consent and verbal informed consent were
taken from patients and controls. Statistical analysis was
performed using SPSS version 20.0
(IBM Corporation, Armonk, NY). Test results were
expressed
as mean ± standard deviation (SD). The distribution of
the variables was tested using the Kolmogorov–
Smirnov test. The chi-square test was used to compare
groups for gender and nasal corneal epithelial staining.
Independent-samples T test was used to compare the
groups for age. For BUT and ST2 values, the Kruskal–
Wallis one-way test was used to test the difference
among groups and Mann–Whitney U test was used to
compare groups. In all analyses, p values <0.05 were
considered as statistically significant.
3. Results
There was no significant difference in age and gender
be- tween inflamed pinguecula and control groups � (p
0.862 and� p 0.794, respectively) (Table 1). Thirty-two
eyes of 32 patients had inflamed pinguecula. All
inflamed pingueculae were on the nasal conjunctiva
(Figure 1). There were pin- guecula in 13 (40 %) and
pterygium in 3 (9%) of the fellow eyes (n 32). There
�
was no pinguecula or pterygium in the control group.
Twenty-three eyes (72%) had punctate epithelial
staining (PES) or epithelial defect on the nasal cornea in
eyes with inflamed pinguecula (Figures 2(a) and 2(b)).
There was one eye (3.1%) with corneal PES in the
fellow eyes group. The difference was statistically
significant (p < 0.001). There was no corneal PES or
epithelial defect in the control group.
The mean values of TBUT tests of eyes with inflamed
pinguecula, fellow eyes, and control eyes were 8.1 ± 3.9
s, 9.3 ±
4.3 s, and 13.5 ± 4.9 s, respectively (Table 2). The eyes
with inflamed pinguecula had significantly lower TBUT
values compared to the control group (p < 0.001). Fellow
eyes also had lower TBUT values than the control
� group
(p 0.003). There was no significant difference in the
TBUT results be- tween eyes with inflamed pinguecula
and fellow eyes (p 0.286). The mean values of ST2
� of eyes with inflamed pinguecula, fellow eyes, and
results
control eyes were 11.6 ±
5.1 s, 11.6 ± 5.3 s, and 17.6 ± 7.8 s, respectively. The
eyes with inflamed pinguecula had significantly lower
ST2 values compared to the control group (p < 0.001).
Fellow eyes also had lower ST2 values than the control
group (p 0.003). There was no significant difference� in
the ST2 results between the eyes with inflamed
pinguecula and fellow eyes (p � 0.951).
4. Discussion
Pinguecula is a common disease of the conjunctiva
whose exact etiology is unknown. UVR is reported to
diagnostic dye com- monly used in ophthalmic
practice. Although the underlying cellular mechanism
of corneal staining is incompletely understood,
fluorescein staining of the ocular surface is a
common diagnostic feature of ocular diseases, and it
is
 TABLE 1: Demographic characteristics of groups.
Inflamed pinguecula group (n � 32) Control group (n � 32) p
Age (years) (mean ± SD) 32.78 ± 10.35 32.31 ± 11.07 0.862a
Female, n (%) 21 (65.6%) 20 (62.5%) b
Sex 0.794
Male, n (%) 11 (34.4%) 12 (37.5%)
a
Independent-samples T test; bchi-square test; p value <0.05 is statistically significant.

FIGURE 1: An inflamed pinguecula.

(a) (b)

FIGURE 2: (a) Epithelial defect and (b) fluorescent staining in a patient with
inflamed pinguecula.

TABLE 2: Schirmer 2 and TBUT test results of the groups.

Patient eyes with

inflamed Patient eyes p# for
Control eyes intergroup
pinguecula (n � without inflamed
� (n 32)
pinguecula (n �32) p∗ comparisons
32) (Group 1)
(Group 2) (Group 3) Groups Groups
Groups 1 vs 2
1 vs 3 2 vs 3
Mean ± SD 8.1 ± 3.9 9.3 ± 4.3 13.5 ±
BUT (s) Median 8.0 8.0 4.9 <0.005 0.286 <0.001 0.003
14.0
Range 3–19 3–18 4–25
Mean ± SD 11.6 ± 11.6 ± 17.6 ±
ST2 Median 5.1 5.3 7.8 <0.005 0.951 <0.001 0.003
(mm) 11.0 10.5 20.0
Range 3–22 2–21 4–30
∗
p value for comparison among three groups (Kruskal–Wallis one-way test). #p values for intergroup comparisons (Mann–Whitney U
test). p value <0.05 is statistically significant.
frequently used to assess ocular surface integrity,
particularly the cornea [13, 14]. A high rate of nasal
corneal PES or epithelial defect was present in the
inflamed pinguecula group compared to fellow eyes and
control group in our study. This finding was not
reported in previous studies. We could not find reports
regarding the fluorescein staining of the nasal cornea in
pinguecula patients in our literature review. The
pathogenesis of this staining may be similar to dellen
formation in which corneal thinning occurs usually
close to limbus due to reduced tear film spread over a
focal corneal area and is usually associated with an
adjacent focal conjunctival or corneal elevation.
Reduced tear break-up time was also reported to be
associated with dellen formation [15]. In dry eye
patients, corneal fluorescein staining usually occurs
symmetrically on the corneal surface without a pre-
dilection for a specific part [16]. Our study suggests that
an inflamed and elevated pinguecula may affect the
distribution of the tear film and cause a desiccated
epithelium in the nasal cornea close to the limbus. Also,
impaired tear function evidenced by lower TBUT and
ST2 results in these patients may aggravate this
situation. These factors together may cause epithelial
cell damage and staining in the nasal cornea. There may
be other effects of inflammation on the nasal corneal
epithelium other than affecting tear film spread since
previous reports on pinguecula without inflammation
did not report nasal corneal fluorescein staining. The in-
flammatory cells and mediators may cause epithelial
cell damage or may affect the epithelial healing in
inflamed pinguecula patients.
Og˘uz et al found that eyes with pinguecula have
signif- icantly lower TBUT values compared to the
healthy controls [11]. Schirmer 1 test (ST1) results were
not significantly different between the eyes with
pinguecula and control group in their study. Dong et al.
found that TBUT values improved after pinguecula
excision, but ST1 results did not change [5]. Both
TBUT and ST2 results were significantly lower in the
eyes with inflamed pinguecula and fellow eyes
compared to the control group in our study. TBUT
measurements have inherent variability, and taking
multiple readings and aver- aging the results is one way
of improving repeatability [17]. Therefore, we used
averaging the multiple readings in our study. Similar to
these studies, TBUT values were also lower in our
study. But unlike them, we also found lower ST2
results. This may be due to difference in study
population since we investigated only patients with
inflamed pinguecula. The results of our study indicate
that both tear film stability and tear production were
affected in patients with inflamed pinguecula. Balogun
and coworkers compared the TBUT values of pterygium
and pinguecula patients and healthy controls. The mean
TBUT values were not significantly dif- ferent between
pinguecula group and healthy controls [18]. The
inclusion of only inflamed pinguecula patients in our
study and the differences in the geographic location and
age of the participants may explain the different
findings of Bola- gun’s study and the present one.
To understand whether inflamed pinguecula causes
abnormalities of tear film or tear film abnormalities
cause inflammation of the pinguecula, we compared the
test re- sults of these patients with those of the fellow
eyes. We found
that the TBUT and ST2 results are not
significantly different between the eyes with inflamed
pinguecula and fellow eyes. Fellow eyes also had
abnormalities of the tear film function, and nearly
50% of these eyes had uninflamed pinguecula (40%)
or pterygium (9%). Considering one of our
diagnostic criteria of inflamed pinguecula “patients
description of a recent increase in ocular redness”
together with these results of the fellow eyes, we think
that abnormality of the tear film may be present before
the inflammation of pin- guecula similar to current
results of fellow eyes. Our study suggests that
impaired tear film together with mechanical irritation
of this elevated tissue makes pinguecula prone to
inflammation.
Pterygium is a triangular growth of conjunctival
fibro- vascular tissue onto the cornea. Specific stimulus
leading to pterygium formation is still unknown [19].
Although there are similarities in the pathogenesis and
histopathological findings of these two ocular surface
diseases, it is still unknown if pinguecula is a precursor
of pterygium and if so, what causes it to progress to
pterygium [1, 6]. Dong et al. reported that abnormal
epithelial differentiation is present in pinguecula tissue
and that pinguecula epithelium has proliferative ca-
pacity exhibiting characteristics of squamous
proliferative diseases [5]. There are also several reports
indicating the role of inflammatory cytokines and
growth factors (GFs) in the pathogenesis of pterygium
[19–21]. These GFs and cytokines are also important in
the normal corneal wound healing and overexpressed in
pterygia. Interleukin-1 and epidermal growth factor
were reported to be important, and they have an additive
effect on corneal epithelial cell migration in corneal
epithelial wounds [22]. Epidermal growth factor was
also shown to induce cell migration in pterygium
epithelium and fibroblasts [20]. Kim et al. emphasized
the importance of myofibroblasts in pterygium
formation [23]. They stated that pterygium may be a
product of an exaggerated repair process after injury to
the ocular surface and prolonged inflammation leading
to tissue damage and fibrosis. They also emphasized the
importance of stromal cell-derived factor-1 and trans-
forming growth factor-beta with other GFs and
inflammatory mediators in the activation of pterygium
fibroblasts. These studies mainly emphasize the
importance of inflammatory cytokines and GFs in the
pterygium formation and that the pterygium may be an
exaggerated repair process.
Archila and Arenas stated that exposure to chronic
solar radiation causes alteration of conjunctival stroma
and leads to pinguecula formation. This causes
disruption of tear film and an area of dryness which
results in drying of conjunctiva and formation of
microulcers on the epithelium. Then, as a part of
protective changes, conjunctiva tries to cover erosion and
leads to pterygium formation [24]. Based on the
literature, our results suggest that abnormal tear film and
improper lubri- cation together with ocular surface
irregularity due to pin- guecula may cause inflammation
of the pinguecula, and these factors cause epithelial
defects on the nasal cornea. In- flammation and corneal
epithelial damage may cause release of GFs and
cytokines which act together to close the wound and
relieve the inflammation in these patients. UVR was
reported to cause limbal stem cell failure on the nasal
cornea [10]. When corneal healing does not occur
properly due to limbal stem cell failure, a prolonged
inflammatory response and exaggerated wound healing
process may occur, and these mediators act on
pinguecula epithelium and stroma, leading to
proliferation towards the nasal cornea to close the
wound. Our study suggests that nasal corneal epithelial
damage in inflamed pinguecula patients may be a
stimulus for exaggerated wound repair causing the
release of GFs leading to growth of con- junctival
epithelium onto the cornea. Inflamed pinguecula patients
with impaired ocular surface lubrication and nasal
 corneal epithelial defects may be a subgroup of
pinguecula patients who have a propensity to progress
to pterygium.
Our study is a cross-sectional study, and it is a
limitation of our study. Another limitation is that we
did not perform histologic or cytologic examination.
The diagnosis of pin- guecula is mostly clinical, and
due to typical appearance, diagnosis of pinguecula is
usually easy but sometimes other pathologies can
mimic pinguecula.
In conclusion, to our knowledge, this is the first
study evaluating corneal staining properties and tear
functions in inflamed pinguecula patients. In a high
percentage of inflamed pinguecula groups, we found
nasal corneal epi- thelial staining or epithelial defect.
We found lower TBUT and ST2 results in this group.
These findings may be im- portant in uncovering the
relation of pinguecula and pterygium and also in their
pathogenesis. Inflammation, corneal epithelial integrity,
and impaired tear film param- eters may be important
factors in the evolution of the pinguecula to pterygium.
Data Availability
The data used to support the findings of this study are
available from the corresponding author upon
request.
Conflicts of Interest
There are no financial and personal relationships with
other people or organizations that could inappropriately
influence the present study. The authors have no
commercial, pro- prietary, and financial interest in the
material presented in this manuscript.
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