The Ocular Surface 18 (2020) 396–402

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The Ocular Surface

journal homepage: www.elsevier.com/locate/jtos

Review Article

Giant papillary conjunctivitis: A review T

∗
Sarah E. Kenny, Cooper B. Tye, Daniel A. Johnson, Ahmad Kheirkhah
Department of Ophthalmology, Long School of Medicine, University of Texas Health at San Antonio, San Antonio, TX, USA

A B S T R A C T

Giant papillary conjunctivitis (GPC), which is characterized by the development of “giant” papillae on the superior tarsal conjunctiva, is a common complication in
contact lens wearers. This condition can be associated with excessive mucus production, itching, blurry vision, and diminished contact lens tolerance. Risk factors for
GPC include non-disposable lenses, infrequent lens replacement, long wearing time, inadequate lens hygiene, and atopy. Although the exact pathophysiology of GPC
remains incompletely understood, it likely develops from the combination of mechanical trauma to the superior tarsal conjunctiva and an immunologic response by
the conjunctiva to deposits on the anterior surface of the contact lens. With proper management, GPC has an excellent prognosis. In mild cases, prompt contact lens
cessation is sufficient for the resolution of signs and symptoms. For more severe cases, the use of topical anti-histaminic agents is indicated. Uncommonly, topical
steroids, non-steroidal anti-inflammatory agents, immunomodulatory medications, or very rarely surgery may be needed. In this review article, we provide a
comprehensive review of the available literature on GPC, with an emphasis on recent findings and treatment advances for this common condition.

1. Introduction 2. Method of literature selection

Giant papillary conjunctivitis (GPC), first described by T.F. Spring in
1974 [1], is a form of ocular inflammatory disease which is char-
acterized by the presence of “giant” papillae on the superior tarsal
conjunctiva [2–4]. Originally, the term “giant” papillae represented any
papillae of 1.0 mm or greater in diameter; however, more recent lit-
erature considers that GPC may be characterized by any papillae with
diameter of 0.3 mm or larger [5]. Although GPC is most commonly
associated with contact lens wear, it may occur with ocular prosthetics,
exposed sutures, exposed scleral buckles, glaucoma filtering blebs, and
elevated band keratopathy, among others. In cases where GPC has been
induced by contact lens wear, it has also been referred to as contact
lens-induced papillary conjunctivitis (CLPC) [6–8].
The exact pathophysiology of GPC is not well understood and it
likely has a multifactorial etiology, involving immunologic responses to
foreign bodies such as contact lenses and clinical manifestations that
surpass the physiologic inflammation induced by the foreign body
[9–11]. Patients usually complain of increased mucus production,
itching, blurry vision, foreign body sensation, diminished contact lens
tolerance, and increased lens awareness [12,13]. Despite education by
eye care providers regarding frequent contact lens replacement and
proper hygiene, GPC continues to be one of the most common com-
plications related to both soft and rigid contact lens wear [14]. In this
article, we provide a comprehensive review of the available literature
on GPC, with more emphasis on recent findings about this condition.
Although giant papillae may also be seen in vernal keratoconjunctivitis
(VKC), our review does not include the literature on such cases.
A primary literature search was conducted in PubMed using the
keywords giant papillae and giant papillary conjunctivitis. A secondary
literature search was conducted by reviewing the references of the in-
itially included articles. We included articles up to December 2019.
3. Etiology/incidence/risk factors
To better understand the etiology of GPC, investigators sought to
determine the incidence and predisposing factors that may precipitate
the development of GPC. Most of the information available on these is
related to GPC in contact lens wearers as discussed below. In fact, GPC
due to other conditions is rare [5].
The reported incidence of GPC in contact lens wearers varies widely
by study. Incidence rates of 1.5%–47.5% have been reported in the
literature [15–18]. The incidence of GPC appears to be influenced by
the frequency of contact lens replacement, type of contact lens, in-
creased wearing time, poor contact lens hygiene, increased lens size,
and poor lens fit [2,3,18–22]. Santodomingo-Rubido et al. found that
GPC developed less frequently in patients using daily wear contact
lenses (7.4%) compared to patients who wore contact lenses for 30 days
(17.0%) [23]. This finding was also concluded in a study by Porazinski
and Donshik where GPC was found in 36% of the group that changed
their lenses monthly and in 4.5% of those who changed their contact
lenses at intervals of every three weeks or less [18]. Furthermore, an
early study by Lustine et al. showed that irregular or infrequent lens
replacement and mediocre lens hygiene are two predominating risk

∗
Corresponding author. Medical Arts and Research Center, 8300 Floyd Curl Dr., San Antonio, TX, 78229, USA.
E-mail address: Kheirkhah@uthscsa.edu (A. Kheirkhah).

https://doi.org/10.1016/j.jtos.2020.03.007
Received 15 February 2020; Accepted 29 March 2020
1542-0124/ © 2020 Elsevier Inc. All rights reserved.
S.E. Kenny, et al.
factors for GPC [24].
The type of contact lens also plays a role in the incidence of GPC.
Although GPC was initially described following the use of hydrophilic
contact lenses [1], the condition has since been associated with a wide
variety of contact lens materials. GPC is more common with soft contact
lenses than with rigid lenses [6]. Wearing soft contact lenses is also
associated with an earlier onset of symptoms and an increased disease
severity when compared to the use of rigid contact lenses [25,26]. The
incidence of GPC among silicone hydrogel lenses is similar to that of
hydroxyethylmethacrylate (HEMA)-based hydrogel lenses [6]. How-
ever, silicone hydrogel contact lenses are more likely to have localized
GPC rather than generalized GPC (see below) [6]. Moreover, the in-
cidence has been found to be lower in disposable contact lenses when
compared to conventional non-disposable lenses. In a study by Poggio
et al., the incidence of GPC was 3.4% in conventional non-disposable
daily wear lenses and 1.2% in disposable daily wear contact lenses [30].
A study by Boswall et al. found a similar trend, with 34% of conven-
tional non-disposable extended lens wearers having GPC, as compared
to only 5% of disposable extended lens wearers [31].
There has been an association between atopy and GPC. Donshik
et al. found that the signs and symptoms of GPC are more severe in
atopic patients compared to non-atopic patients [6,26]. A correlation
between seasonal onset of allergies and GPC was also noted by Begley
et al. [32] Moreover, Porazinski and Donshik conducted a retrospective
review of frequent replacement contact lens wearers and found that
patients with GPC were significantly more likely to report a history of
allergy [18]. More recently, Tagliaferri et al. studied a large group of
patients who wore contact lenses continuously for up to 30 days and
found that 25% of patients developed GPC whose timing correlated
with the seasonal peaks in environmental allergens [33]. In the same
study, GPC was found not to be associated with history of prior GPC,
race, sex, or lens-to-cornea fitting relationship [33].
4. Pathophysiology
The exact pathophysiology of GPC remains incompletely under-
stood; however, this condition likely develops from the combination of
mechanical trauma to the superior tarsal conjunctiva and an im-
munologic response by the conjunctiva to deposits on the anterior
surface of contact lens [5,9,10,13,21,34–36]. Although GPC most often
occurs with contact lens wear, the condition may also be seen in other
circumstances, including ocular prosthetics, exposed sutures, extruded
scleral buckles, dermoid tumors, and cyanoacrylate adhesives
[21,36–38]. As such, it has been postulated that the etiology is multi-
factorial, involving mechanical trauma to the conjunctiva and an im-
mune reaction involving both immediate and delayed hypersensitivities
[1,39]. In the former, conjunctival mast cells bound by IgE mount a
nonspecific response to a presenting antigen. With time, the adaptive
immune response is mounted by lymphocytes against the specific an-
tigen. Tissue inflammation and further infiltration of inflammatory
cells, including mast cells, eosinophils, and basophils, ensues [40].
Based on the findings of mast cells, eosinophils, and basophils in the
conjunctival epithelium, along with an increased number of plasma
cells, lymphocytes, and polymorphonuclear leukocytes in the stroma,
Allansmith et al. postulated that there is an immunologic basis for GPC
[12,13]. Further bolstering this idea, demonstration of elevated levels
of neutrophil chemotactic factors in the tears [41] and IgM deposition
on contact lenses [42] of symptomatic patients have further contributed
to the theory of immunologic origin. A study by Moschos et al. also
showed elevated levels of eotaxin, a potent eosinophil chemotactic
agent, in the tears of symptomatic patients with GPC. Eotaxin also ac-
tivates the respiratory burst associated with eosinophils. Thus, in-
creased levels of eotaxin can lead to increased recruiting and activation
of eosinophils in affected patients. The study by Moschos et al. noted a
linear correlation between the quantitative amounts of eotaxin present
in tears and the severity of symptoms of patients [43].
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The Ocular Surface 18 (2020) 396–402
Patients with GPC also show increased levels of interleukins 2, 4, 6,
8, and 11, RANTES, IgM, macrophage-colony stimulating factor (M-
CSF), and other inflammatory cytokines on both conjunctival tissue and
tear examination [41,42,44,45]. In patients with bilateral GPC but
asymmetric eye symptomatology, the expression of IgE was found to be
higher in the more symptomatic eye [46]. Decay accelerating factor
(DAF), which normally inhibits C3 complement activation and is typi-
cally found in tears and conjunctival samples, is also decreased in pa-
tients with GPC, causing an increase in complement activation in af-
fected patients [6,47]. The expression of leukotriene C4, known to
cause excess mucus production, edema, conjunctival injection, and
papillary formation, has been found to be elevated in tear fluid of soft
contact lens-induced GPC [48–50].
These increased levels of complement activation, interleukins, and
inflammatory cells are proposed to be responsible for the acute for-
mation of papillae in patients with GPC [6,43,44,51]. Chronically, pa-
tients with GPC develop stromal fibrosis and decreased cellularity [52].
Additionally, Xingwu et al. described the presence of M cells in the
conjunctiva-associated lymphoid tissue (CALT) of papillae and follicles
from the upper tarsal tissue of patients with GPC [53]. The presence of
these M cells, which are normally involved in upregulating immune
responses through the uptake and transport of antigens to upstream
immune cells, further supports the etiology of immune origin in GPC
[53]. Xingwu et al. postulated that these cells act as “sensors” on the
ocular surface and may translocate antigenic materials to B cells, in-
ducing an inflammatory response and the subsequent signs and symp-
toms of GPC [53].
Taken together, the increased levels of immune cells and associated
inflammatory proteins present in patients with GPC bolster the case for
an immunologic cause. However, it is not fully understood what drives
this immunologic reaction in these patients. It has been hypothesized
that the accumulation of protein deposits on contact lenses (see below)
may initiate the development of GPC in vulnerable individuals by
acting as antigenic stimuli [54,55]. These vulnerable individuals may
include those with a history of atopy and those who do not clean or
change their contact lenses frequently enough [13]. Several other stu-
dies have similarly shown that the accumulation of proteinaceous
debris on the anterior surface of the contact lens traumatizes the upper
conjunctiva and physically perturbs the epithelium, which results in the
aforementioned cellular and humoral immunologic response in the
conjunctival epithelium [10,56,57].
In summary, the above-mentioned studies bolster the idea that GPC
is multifactorial in nature. It seems that a history of atopy, poor lens
care, improper type of lens, and mechanical trauma all play a part in an
individual's development of GPC.
Lens deposits
Proteinaceous deposits, which occur on the anterior surface of all
worn contact lenses, have been implicated to induce an immunologic
response that results in the clinical manifestations of GPC. Fowler and
Allansmith examined the contact lens deposits of patients who wore
their contact lenses continuously for an average of 8 months and
compared them to those of patients who regularly cleaned their lenses
daily or weekly for at least 6 months. They found that continuously
worn therapeutic contact lenses were more thickly and uniformly
coated with proteinaceous deposits than cosmetic, routinely cleaned
contact lenses [58]. Furthermore, the amount and complexity of de-
posits coating the contact lens increased as the contact lenses were used
for longer periods of time [59].
Numerous studies have examined the histologic makeup of deposits
on various types of contact lenses [60–68]. In wearers without GPC, the
predominant protein present in the contact lens deposits was lysozyme,
and in lesser amounts, IgA, lactoferrin, IL-6, IL-8, and IgG, which are
found physiologically in tears [69]. Jones et al. found that contact
lenses take up tear proteins onto their surfaces upon placement onto
S.E. Kenny, et al.
individual's eyes, thus the composition of proteins found in tears often
mimics those found on the lenses themselves [70]. Other factors asso-
ciated with deposition of proteins on lenses include the surface quality
of the lens [71], lens pore size [72], and the charge of the proteins
present [64,72–74].
Microscopically, the presence of a thick, mucus-like material on
contact lenses is seen in patients both with and without GPC after just
30 minutes of lens wear [54,59]. Richard et al. measured the expression
levels of lysozyme, lactoferrin, and immunoglobulin in the deposits of
contact lenses belonging to both active GPC and non-GPC patients; they
found no statistically significant difference in these protein levels be-
tween the two groups [42]. However, significantly higher levels of
human serum albumin have been detected in deposits on extended-
wear contact lenses of patients with GPC [75].
Despite similar expression of lysozyme on contact lenses in both
GPC and non-GPC cases, the lysozyme deposited on contact lenses of
patients with GPC has been shown to be denatured, which may prompt
the immunologic response responsible for the signs and symptoms of
the condition [76–78]. Moreover, histologic examination of protein
deposits of silicone hydrogel contact lenses have shown that, although
silicone hydrogel lenses have lower levels of lysozyme deposition than
conventional lens material, the lysozyme that is present is largely de-
natured [76–79]. A recent study by Boone et al. also showed that all
silicone hydrogel lenses deposit protein with varying levels of lysozyme
denaturation [79].
The mechanism by which protein deposits starts or accentuate the
inflammatory process in GPC remains to be discovered.
5. Histologic pathology
Histologically, conjunctival tissue obtained from individuals with
GPC show a thickened and irregular epithelium with frequent presence
of erosions. There are pleomorphism and polymegathism of epithelial
cells [5]. The number of goblet cells seems to be increased [5]. There is
an abundance of inflammatory cells that comprise a complex, mixed
cellular infiltrate [80]. Mast cells, eosinophils, and basophils are com-
monly found in increased levels in epithelial samples, while stromal
samples show predominantly eosinophils and basophils [2,13,39]. It
has been demonstrated that the mast cells present in the conjunctival
epithelium of patients with GPC belong to a subset of mast cells (MCtc)
that are known to operate within the skin and mucosa of the small
intestine [5]. In patients with GPC, a significant percentage of the mast
cells have degranulated, leading to elevated levels of tear tryptase
[81,82]. Additionally, tear samples from affected patients also de-
monstrate increased levels of eosinophils and neutrophils [83]. Lym-
phocytes and plasma cells are also present in the conjunctiva of in-
dividuals with GPC, and their numbers are increased from control
tissues samples [5,84]. Moreover, conjunctival T lymphocytes have
increased expression of markers involved in antigen presentation, in-
cluding CD4+, CD45RO+, and HLA-DR+ [80].
6. Clinical manifestations
GPC is characterized clinically by the presence of giant papillae on
the tarsal plates, conjunctival injection, and thick mucus deposits in
both the tear film and medial canthal region [5,12,22]. However, it is
noteworthy that papillae are often present even in asymptomatic, non-
contact lens-wearing patients; a study by Allansmith et al. found that
small, uniform papillae are found in 69% of healthy subjects without
contact lenses [13]. Korb et al. found that 0.6% of patients who did not
wear contact lenses or experience GPC displayed conjunctival papillae
over 0.3 mm [85]. The presence of giant papillae in combination with
the common presenting symptoms, described below, will lead a clin-
ician to suspect GPC.
The most common presenting symptoms of GPC include itchiness,
blurry vision, excessive mucus production in the tear film, foreign body
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sensation, and decreased lens tolerance and wearing time [9,10]. Not
all patients with GPC experience all of these symptoms, and patients’
complaints may range from minimal itchiness to a complete inability to
tolerate contact lenses [29]. Signs of GPC include excess mucus pro-
duction, hyperemia, conjunctival opacification, and multiple giant pa-
pillae that measure 0.3 mm or greater in diameter and are highlighted
by fluorescein staining [5,37]. Larger papillae often have an overlying
white “caps” that regress as the condition improves and are likely due
to inflammatory infiltrates in the conjunctival epithelium [5]. Although
signs and symptoms are usually present bilaterally, one study found
that 10% of GPC cases were unilateral [46].
GPC may develop months, or even years, after successful and
asymptomatic contact lens wear [2]. It appears that there is a shorter
time to onset of GPC in soft contact lens wearers compared to rigid
contact lens wearers. In a study in 1977, Allansmith et al. reported that
the average length for the onset of GPC following contact lens initiation
was 10 months in soft contact lens users, compared to a range of 14
months to 9 years in the group that wore hard contact lenses [13].
Additionally, Donshik et al. found that symptoms are more severe in
patients with soft contact lenses [25,26].
In those individuals developing GPC due to contact use, character of
the papillae depends on the type of contact lens worn. Allansmith et al.
observed that the papillae associated with soft contact lens wear pro-
gressed from small clusters to elevated, giant papillae with a flattening
of the top surface and a “mushroom” appearance [13]. Conversely,
rigid contact lens wearers typically develop fewer papillae, which are
often crater-like [5].
There are variations in distribution of the giant papillae on the
upper tarsal conjunctiva based on the type of contact lens [13]. Al-
lansmith et al. reported that in soft contact lens wearers, the papillae
usually are located initially in zone 1 of the superior tarsal conjunctiva,
which is along the upper tarsal border, with subsequent spread to re-
maining areas [13]. In rigid contact lens wearers, papillae can be seen
alone in zones 2 (central area of the tarsal plate) and 3 (along the lid
margin), but are never observed solely in zone 1 [85]. In cases of GPC
attributed to exposed sutures, filtering blebs, and elevated band kera-
topathy, the papillae have been noted to localize in the region of the
superior tarsal conjunctiva directly overlying the inciting pathology
[5,38]. Cases of GPC attributed to scleral lenses or prosthetic shells are
often characterized by papillae on the tarsal surface and in the superior
fornix [5].
In another study, Holden differentiated cases of GPC based on
whether the papillae were confined to one or two zones of the tarsal
conjunctiva (“local”) or spread across more than two areas of the
conjunctiva (“general”) [86]. More recently, Skotnitsky et al. conducted
larger-scale studies confirming the existence of these local and general
clinical presentations of GPC [7,27]. Both forms display increased hy-
peremia and enlarged papillae [7,27].
Allansmith et al. proposed four stages of clinical manifestations of
GPC that develop as the condition progresses. Initially, in Stage 1,
symptoms cause minimal discomfort and include itchiness and mucus
in the nasal corner of the eye [2]. Patients often do not present to their
eye care provider until Stage 2, wherein they report increased lens
awareness and mildly blurred vision. These symptoms grow more se-
vere in Stage 3 and cause significant itching, mucous discharge, and
diminished ability to continue lens wear. In Stage 4, patients become
completely intolerant of lens wear due to foreign body sensation,
clouded lenses, and the presence of stringing mucus [2,34].
Complications that extend beyond these clinical manifestations are
rare. Two separate case reports describe pediatric patients who pre-
sented with ptosis, which, along with associated symptoms of GPC,
resolved following lens removal [87,88]. Beljan et al. postulated that
the ptosis may be caused by the edema that results from manipulation
of and pressure on the eyelids during contact lens placement and re-
moval [89]. In the most severe cases of GPC, a breakdown of superior
corneal epithelium may occur [3].
S.E. Kenny, et al.
7. Management/prevention
Despite the introduction and extensive adoption of daily contact
lenses, GPC continues to be a significant reason for contact lens cessa-
tion by patients [33]. In fact, it has been reported that this condition is a
common reason for discontinuation of contact lens wear [90]. While
there are numerous clinical trials that examine treatments for various
forms of ocular allergic diseases, most studies on GPC management
modalities do not meet the criteria for randomized controlled trials,
making it difficult for eye care providers to implement evidence-based
treatment protocols in their practice [91].
Elimination of the inciting agent, such as broken suture or exposed
scleral buckle, will lead to resolution of the related GPC. Since contact
lens wear is responsible for the initial trauma and inflammatory reac-
tion in most cases of GPC, temporary contact lens wear discontinuation
is the first step of management [8]. Discontinuation of contact lens
wear has been recommended for 2–4 weeks, or until signs and symp-
toms resolve [6,92,93]. Following this period, if possible, eye care
providers should refit the patient with either daily disposable soft
contact lenses or soft contact lenses that are replaced on an interval of
1–2 weeks [6].
Skotnitsky et al. recommended a slightly different approach, de-
pending on whether the patient has local or general GPC. They sug-
gested that patients with local GPC may continue contact lens wear if
they are prescribed with a new pair of contact lenses of the same or
alternate type [7]. However, if symptoms persist or recur, the eye care
provider should prescribe daily disposable or frequent replacement
contact lenses [7]. General GPC may be managed by discontinuation of
contact lenses until symptoms have completely resolved and papillae
have decreased in both size and intensity [7].
If switching to more frequent replacement of the lens is not possible,
for example due to the cost or in cases of rigid-gas permeable contact
lenses, appropriate contact lens hygiene becomes of paramount im-
portance. In order to establish an uncomplicated contact lens wear, it is
important for patients to adhere to regular and effective contact lens
hygiene practice. Several studies have examined various contact lens
cleaning regimens and their effects on protein and lipid deposits on the
contact lens [12,39]. Zhu et al. studied the outcomes of the “rub and
rinse” technique for cleaning contact lenses and found it to be effica-
cious for reducing bacterial load and removing tear deposits on worn
contact lenses, although the study did not focus specifically on patients
affected by GPC [94]. The use of polyhexamethylene biguanide solution
to remove protein depositions was also studied by Luensmann et al.,
however this solution did not show any significant improvement in
protein removal compared to control lenses [95]. Donshik et al. re-
commended daily contact lens cleaning with hydrogen peroxide and
unpreserved saline solution, and once-to twice-weekly enzymatic
cleaning of contact lenses that are replaced at intervals of more than
two weeks [6].
Of note, Donshik et al. found that in a group of patients with GPC
who continued to wear contact lenses and simply changed the cleaning
regimen, only 50% were able to continue to wear their contact lenses in
the long term [26]. Decreasing the wearing time of contact lens can
play an important role in management of GPC. Furthermore, contact
lenses with poorly designed edges should be avoided due to possible
additional trauma to the conjunctiva. A switch from soft contact lens to
rigid gas-permeable contact lens may also be considered if other mea-
sured have failed to cause resolution of signs and symptoms of GPC [5].
Anti-allergic therapies are often used to treat GPC during the tem-
porary period of contact lens discontinuation [6,96–98]. These include
antihistaminic agents, mast cell stabilizers, or dual-acting agents. To-
pical cromolyn sodium, a mast cell stabilizer, has been shown to be
effective for GPC along with a proper lens hygiene. Meisler et al. found
that cromolyn sodium is effective for treating symptoms and reducing
the size and prominence of papillae that may remain following
symptom resolution [99]. Kruger et al. also demonstrated the efficacy
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The Ocular Surface 18 (2020) 396–402
of cromolyn sodium in a group of patients who failed to respond to
initial management of contact lens wear discontinuation, robust hy-
giene, and refitting with a different contact lens type [100]. Cromolyn
can be applied to the eye while wearing contact lens [5]. Lodoxamide,
another mast cell stabilizing agent, has also been shown to significantly
decrease the levels of leukotriene B4 and leukotriene C4 levels in pa-
tients with ocular prosthetic-associated GPC [101]. Fahy et al. found
lodoxamide to be more effective and rapidly acting than cromolyn so-
dium for treating GPC [102]. Numerous other studies have shown that
other antihistamines or dual-acting agents, including alcaftadine, olo-
patadine, emedestine, ketotifen and bepotastine are safe and effective
for symptom relief, especially itching, in patients with GPC
[98,103–105].
When anti-allergic medications do not sufficiently improve symp-
toms, or in severe cases of GPC, steroid eye drops can be an appropriate
therapeutic option [8]. To reduce steroid-related side effects, such as
increased intraocular pressure (IOP), “soft steroids” can be a proper
choice for this indication. Two studies examined the safety and efficacy
of loteprednol etabonate 0.5% for GPC and found that it significantly
improved ocular itching and lens intolerance and decreased the mag-
nitude of papillae [106,107]. In both studies, patients received lote-
prednol etabonate 0.5% four times a day for six weeks. Saurbhi et al.
compared the efficacy of olopatadine (a dual-acting agent) and fluor-
ometholone (a steroid) for the treatment of mild to moderate GPC in a
randomized, double-masked study. For eight weeks, the patients re-
ceived twice daily therapy of olopatadine 0.1%, fluorometholone 0.1%,
or both. The three groups showed comparable improvement of ocular
redness, itching, tearing, and contact lens tolerance. Olopatadine and
fluorometholone in combination was initially more effective than either
medication alone, but at the conclusion of the study, the three groups
had comparable improvement in signs and symptoms of GPC [108].
Topical non-steroidal anti-inflammatory drugs (NSAIDs) are another
treatment option for individuals with GPC due to their reduction in
prostaglandins. Several studies have shown NSAIDs to be efficacious at
reducing conjunctival injection and itching in individuals affected by
allergic ocular conditions, including GPC [109–112]. A study by Uchio
found that NSAIDs also play a role in reducing fibroblastic and vascular
endothelial cell activity in individuals with GPC and other allergic
conjunctival diseases through the inactivation of local inflammatory
cells [113]. Due to these effects, NSAIDs could be used as an adjunct to
steroids in individuals with uncontrolled GPC, or as an alternate
therapy to these drugs in individuals with adverse effects to steroids,
including increased IOP [113].
In rare instances where signs and symptoms of GPC persist despite
the above-mentioned management, patients with GPC may require
immunomodulatory therapy. Kymionis et al. reported on a refractory
case of GPC that resolved after one month of tacrolimus 0.03% oint-
ment, which is a calcineurin inhibitor [114]. The case described had not
responded to antihistamines, mast cell stabilizers, topical corticoster-
oids, and surgical resection-cryopexy [114]. Moreover, there are many
reports on the safety and efficacy of topical tacrolimus and cyclosporine
A in treatment of the giant papillae associated with vernal kerato-
conjunctivitis [115–119]. Additional studies are needed to evaluate the
role these immunomodulatory medications in treatment of GPC.
Very rarely, surgery may be needed for severe, refractory cases of
GPC. There is a paucity of data on the surgical approach for such cases;
however, procedures similar to what described for VKC-associated giant
papillae would be reasonable. These include cryotherapy of papillae,
excision of papillae, and excision of papillae followed by either am-
niotic membrane transplantation, autologous conjunctival graft, or oral
mucosal transplantation to cover tarsal defects [25,120–122].
In summary, the primary course of treatment of contact lens-in-
duced GPC is discontinuation of contact lens wear for up to four weeks
[6,123]. Adjunctive therapy, consisting of anti-allergic medications,
may be used [93]. Topical steroids or immunomodulatory agents may
be added to the treatment course for patients whose symptoms persist
S.E. Kenny, et al.
following anti-allergic therapy [106,107,124]. Following contact lens
discontinuation and medical therapy, patients may restart contact lens
wear with a new pair of contact lenses. Ideally, patients should be
prescribed daily disposable contact lenses or contact lenses that are
replaced on a more frequent basis, preferably every two weeks or less
[6].
After a patient with GPC has been treated successfully and is able to
resume contact lens wear, it is important to implement changes that
will lower the risk of recurrence, such as increasing the frequency of
lens replacement and promoting maintenance of lens hygiene
[12,18,25,122,125]. Multiple studies have established that increasing
the frequency of contact lens replacement to 2–3 weeks or less lowers
the risk of developing GPC [18,25,126]. Disposable daily wear contact
lenses may be a more suitable option for patients with a history of atopy
or GPC, since there is a decreased exposure to potentially allergic so-
lutions and cleaners [127]. Although the use of daily disposable contact
lenses may lower a patient's risk of GPC, the condition may still develop
in patients wearing these lenses [21,128–130]. Prescribing a contact
lens of a different polymer type may also be considered for preventing
recurrence [25,26]. In addition, patients must be educated on their
ability to reduce the risk of recurrence by adhering to an appropriate
contact lens wear schedule and cleaning routine. Education by eye care
providers about treatment and recurrence prevention of GPC is critical,
since persistent nonadherence to appropriate contact lens wear and
care is part of the reason why GPC continues to be a significant com-
plication associated with contact lens wear [131]. However, with
proper management, the prognosis of GPC is excellent.
Financial disclosures
The authors have no financial interest in this manuscript.
Funding
None.
Declaration of competing interest
None.
References
[1] Spring TF. Reaction to hydrophilic lenses. Med J Aust 1974;1(12):449–50.
[2] Allansmith MR. Clinical aspects of giant papillary conjunctivitis. Proc Inst Med
Chicago 1981;34(4):106–7.
[3] Farkas P, Kassalow TW, Farkas B. Clinical management and control of giant pa-
pillary conjunctivitis secondary to contact lens wear. J Am Optom Assoc
1986;57(3):197–200.
[4] Leonardi A, Bogacka E, Fauquert JL, et al. Ocular allergy: recognizing and diag-
nosing hypersensitivity disorders of the ocular surface. Allergy
2012;67(11):1327–37.
[5] Dunn SP, Heidemann DG. Giant papillary conjunctivitis. In: Mannis M, Holland E,
editors. Cornea. Elsevier; 2017. p. 542–8.
[6] Donshik PC, Ehlers WH, Ballow M. Giant papillary conjunctivitis. Immunol Allergy
Clin. North. Am 2008;28(1):83–103.
[7] Skotnitsky C, Sankaridurg PR, Sweeney DF, Holden BA. General and local contact
lens induced papillary conjunctivitis (CLPC). Clin Exp Optom 2002;85(3):193–7.
[8] Takamura E, Uchio E, Ebihara N, et al. Japanese guidelines for allergic con-
junctival diseases 2017. Allergol Int 2017;66(2):220–9.
[9] Mackie IA, Wright P. Giant papillary conjunctivitis (secondary vernal) in associa-
tion with contact lens wear. Trans Ophthalmol Soc U K 1978;98(1):3–9.
[10] Childress CM, Nemeth S. A review of contact lens induced giant papillary con-
junctivitis. J Ophthalmic Nurs Technol 1988;7(1):12–7.
[11] Efron N. Contact lens wear is intrinsically inflammatory. Clin Exp Optom
2019;100(1):3–19.
[12] Richmond PP, Allansmith MR. Giant papillary conjunctivitis. Int Ophthalmol Clin
1981;21(2):65–82.
[13] Allansmith MR, Korb DR, Greiner JV, Henriquez AS, Simon MA, Finnemore VM.
Giant papillary conjunctivitis in contact lens wearers. Am J Ophthalmol
1977;83(5):697–708.
[14] Forister JF, Forister EF, Yeung KK, et al. Prevalence of contact lens-related com-
plications: UCLA contact lens study. Eye Contact Lens 2009;35(4):176–80.
400
The Ocular Surface 18 (2020) 396–402
[15] Alemany A, Redal A. Giant papillary conjunctivitis in soft and rigid lens wear.
Contactologia 1991;13:14–7.
[16] Lamer L. Extended wear contact lenses for myopes. A follow-up study of 400 cases.
Ophthalmology 1983;90(2):156–61.
[17] Alipour F, Khaheshi S, Soleimanzadeh M, Heidarzadeh S, Heydarzadeh S. Contact
lens-related complications: a review. J Ophthalmic Vis Res 2017;12(2):193–204.
[18] Porazinski AD, Donshik PC. Giant papillary conjunctivitis in frequent replacement
contact lens wearers: a retrospective study. CLAO J 1999;25(3):142–7.
[19] Molinari JF. The clinical management of giant papillary conjunctivitis. Am J
Optom Physiol Opt 1981;58(10):886–91.
[20] Farkas P, Kassalow TW, Farkas B. The use of enzyme tablets to control grade III
GPC with PMMA lenses. J Am Optom Assoc 1984;55(11):836–7.
[21] Meisler DM, Keller WB. Contact lens type, material, and deposits and giant pa-
pillary conjunctivitis. CLAO J 1995;21(1):77–80.
[22] Hart DE, Schkolnick JA, Bernstein S, Wallach D, Gross DF. Contact lens induced
giant papillary conjunctivitis: a retrospective study. J Am Optom Assoc
1989;60(3):195–204.
[23] Santodomingo-Rubido J, Wolffsohn JS, Gilmartin B. Adverse events and dis-
continuations during 18 months of silicone hydrogel contact lens wear. Eye
Contact Lens 2007;33(6 Pt 1):288–92.
[24] Lustine T, Bouchard CS, Cavanagh HD. Continued contact lens wear in patients
with giant papillary conjunctivitis. CLAO J 1991;17(2):104–7.
[25] Donshik PC. Contact lens chemistry and giant papillary conjunctivitis. Eye Contact
Lens 2003;29(1 Suppl):S37–9.
[26] Donshik PC. Giant papillary conjunctivitis. Trans Am Ophthalmol Soc
1994;92:687–744.
[27] Skotnitsky CC, Naduvilath TJ, Sweeney DF, Sankaridurg PR. Two presentations of
contact lens-induced papillary conjunctivitis (CLPC) in hydrogel lens wear: local
and general. Optom Vis Sci 2006;83(1):27–36.
[29] Dumbleton K. Noninflammatory silicone hydrogel contact lens complications. Eye
Contact Lens 2003;29(1 Suppl):S186–9.
[30] Poggio EC, Abelson MB. Complications and symptoms with disposable daily wear
contact lenses and conventional soft daily wear contact lenses. CLAO J
1993;19(2):95–102.
[31] Boswall GJ, Ehlers WH, Luistro A, Worrall M, Donshik PC. A comparison of con-
ventional and disposable extended wear contact lenses. CLAO J
1993;19(3):158–65.
[32] Begley CG, Riggle A, Tuel JA. Association of giant papillary conjunctivitis with
seasonal allergies. Optom Vis Sci 1990;67(3):192–5.
[33] Tagliaferri A, Love TE, Szczotka-Flynn LB. Risk factors for contact lens-induced
papillary conjunctivitis associated with silicone hydrogel contact lens wear. Eye
Contact Lens 2014;40(3):117–22.
[34] Katelaris CH. Giant papillary conjunctivitis–a review. Acta Ophthalmol Scand
Suppl 1999(228):17–20.
[35] Udell IJ, Meisler DM. Giant papillary conjunctivitis. Int Ophthalmol Clin
1986;26(1):35–41.
[36] Friedlaender MH. Some unusual nonallergic causes of giant papillary con-
junctivitis. Trans Am Ophthalmol Soc 1990;88:343–9.
[37] Srinivasan BD, Jakobiec FA, Iwamoto T, DeVoe AG. Giant papillary conjunctivitis
with ocular prostheses. Arch Ophthalmol 1979;97(5):892–5.
[38] Heidemann DG, Dunn SP, Siegal MJ. Unusual causes of giant papillary con-
junctivitis. Cornea 1993;12(1):78–80.
[39] Richmond PP. Giant papillary conjunctivitis: an overview. J Am Optom Assoc
1979;50(3):343–7.
[40] Allansmith M. Treatment of giant papillary conjunctivitis. In: Flattau E, editor.
Considerations in contact lens use under adverse conditions: proceedings of a
symposium. Washington DC: National Research Council, National Academies Press
(US); 1991. p. 74–83.
[41] Elgebaly SA, Donshik PC, Rahhal F, Williams W. Neutrophil chemotactic factors in
the tears of giant papillary conjunctivitis patients. Invest Ophthalmol Vis Sci
1991;32(1):208–13.
[42] Richard NR, Anderson JA, Tasevska ZG, Binder PS. Evaluation of tear protein
deposits on contact lenses from patients with and without giant papillary con-
junctivitis. CLAO J 1992;18(3):143–7.
[43] Moschos MM, Eperon S, Guex-Crosier Y. Increased eotaxin in tears of patients
wearing contact lenses. Cornea 2004;23(8):771–5.
[44] Shoji J, Inada N, Sawa M. Antibody array-generated cytokine profiles of tears of
patients with vernal keratoconjunctivitis or giant papillary conjunctivitis. Jpn J
Ophthalmol 2006;50(3):195–204.
[45] Calder VL, Jolly G, Hingorani M, et al. Cytokine production and mRNA expression
by conjunctival T-cell lines in chronic allergic eye disease. Clin Exp Allergy
1999;29(9):1214–22.
[46] Fukagawa K, Saito H, Azuma N, Tsubota K, Iikura Y, Oguchi Y. Histamine and
tryptase levels in allergic conjunctivitis and vernal keratoconjunctivitis. Cornea
1994;13(4):345–8.
[47] Szczotka LB, Cocuzzi E, Medof ME. Decay-accelerating factor in tears of contact
lens wearers and patients with contact lens-associated complications. Optom Vis
Sci 2000;77(11):586–91.
[48] Sengör T, Irkeç M, Gülen Y, Taşeli M, Erker H. Tear LTC4 levels in patients with
subclinical contact lens related giant papillary conjunctivitis. CLAO J
1995;21(3):159–62.
[49] Hingorani M, Calder VL, Buckley RJ, Lightman SL. The role of conjunctival epi-
thelial cells in chronic ocular allergic disease. Exp Eye Res 1998;67:491–500.
[50] Irkeç MT, Orhan M, Erdener U. Role of tear inflammatory mediators in contact
lens-associated giant papillary conjunctivitis in soft contact lens wearers. Ocul
Immunol Inflamm 1999;7(1):35–8.
S.E. Kenny, et al.
[51] Choi TH, Ko MK, Choe JK. Increased numbers of Langerhans cell and expression of
HLA-Dr antigen in the giant papilla of patients with giant papillary conjunctivitis.
Kor J Ophthalmol 1996;10(1):18–23.
[52] Sarac O, Erdener U, Irkec M, Us D, Gungen Y. Tear eotaxin levels in giant papillary
conjunctivitis associated with ocular prosthesis. Ocul Immunol Inflamm
2003;11(3):223–30.
[53] Zhong X, Liu H, Pu A, Xia X, Zhou X. M cells are involved in pathogenesis of human
contact lens-associated giant papillary conjunctivitis. Arch Immunol Ther Exp
(Warsz) 2007;55(3):173–7.
[54] Fowler SA, Greiner JV, Allansmith MR. Soft contact lenses from patients with giant
papillary conjunctivitis. Am J Ophthalmol 1979;88(6):1056–61.
[55] Fowler SA, Allansmith MR. The surface of the continuously worn contact lens.
Arch Ophthalmol 1980;98(7):1233–6.
[56] Ballow M, Donshik PC, Rapacz P, Maenza R, Yamase H, Muncy L. Immune re-
sponses in monkeys to lenses from patients with contact lens induced giant pa-
pillary conjunctivitis. CLAO J 1989;15(1):64–70.
[57] Palmisano PC, Ehlers WH, Donshik PC. Causative factors in unilateral giant pa-
pillary conjunctivitis. CLAO J 1993;19(2):103–7.
[58] Fowler SA, Allansmith MR. The effect of cleaning soft contact lenses. A scanning
electron microscopic study. Arch Ophthalmol 1981;99(8):1382–6.
[59] Fowler SA, Allansmith MR. Evolution of soft contact lens coatings. Arch
Ophthalmol 1980;98(1):95–9.
[60] Subbaraman LN, Woods J, Teichroeb JH, Jones L. Protein deposition on a lathe-cut
silicone hydrogel contact lens material. Optom Vis Sci 2009;86(3):244–50.
[61] Nichols JJ. Deposition on silicone hydrogel lenses. Eye Contact Lens
2013;39(1):20–3.
[62] Subbaraman LN, Glasier MA, Varikooty J, Srinivasan S, Jones L. Protein deposition
and clinical symptoms in daily wear of etafilcon lenses. Optom Vis Sci
2012;89(10):1450–9.
[63] Omali NB, Zhao Z, Zhu H, Tilia D, Willcox MD. Quantification of individual pro-
teins in silicone hydrogel contact lens deposits. Mol Vis 2013;19:390–9.
[64] Omali NB, Subbaraman LN, Coles-Brennan C, Fadli Z, Jones LW. Biological and
clinical implications of lysozyme deposition on soft contact lenses. Optom Vis Sci
2015;92(7):750–7.
[65] Poyraz C, Irkec M, Mocan MC. Elevated tear interleukin-6 and interleukin-8 levels
associated with silicone hydrogel and conventional hydrogel contact lens wear.
Eye Contact Lens 2012;38(3):146–9.
[66] van der Worp E, Bornman D, Ferreira DL, Faria-Ribeiro M, Garcia-Porta N,
Gonzalez-Meijome JM. Modern scleral contact lenses: a review. Cont Lens Anterior
Eye 2014;37(4):240–50.
[67] Zhao Z, Carnt NA, Aliwarga Y, et al. Care regimen and lens material influence on
silicone hydrogel contact lens deposition. Optom Vis Sci 2009;86(3):251–9.
[68] Zhao Z, Naduvilath T, Flanagan JL, et al. Contact lens deposits, adverse responses,
and clinical ocular surface parameters. Optom Vis Sci 2010;87(9):669–74.
[69] Gudmundsson OG, Woodward DF, Fowler SA, Allansmith MR. Identification of
proteins in contact lens surface deposits by immunofluorescence microscopy. Arch
Ophthalmol 1985;103(2):196–7.
[70] Jones L, Brennan NA, Gonzalez-Meijome J, et al. The TFOS International
Workshop on Contact Lens Discomfort: report of the contact lens materials, design,
and care subcommittee. Invest Ophthalmol Vis Sci 2013;54(11):37–70.
[71] Castillo EJ, Koenig JL, Anderson JM, Lo J. Characterization of protein adsorption
on soft contact lenses. I. Conformational changes of adsorbed human serum al-
bumin. Biomaterials 1984;5(6):319–25.
[72] Garrett Q, Chatelier RC, Griesser HJ, Milthorpe BK. Effect of charged groups on the
adsorption and penetration of proteins onto and into carboxymethylated poly
(HEMA) hydrogels. Biomaterials 1998;19(23):2175–86.
[73] Garrett Q, Laycock B, Garrett RW. Hydrogel lens monomer constituents modulate
protein sorption. Invest Ophthalmol Vis Sci 2000;41(7):1687–95.
[74] Sack RA, Jones B, Antignani A, Libow R, Harvey H. Specificity and biological
activity of the protein deposited on the hydrogel surface. Relationship of polymer
structure to biofilm formation. Invest Ophthalmol Vis Sci 1987;28(5):842–9.
[75] Tan ME, Demirci G, Pearce D, Jalbert I, Sankaridurg P, Willcox MD. Contact lens-
induced papillary conjunctivitis is associated with increased albumin deposits on
extended wear hydrogel lenses. Adv Exp Med Biol 2002;506(Pt B):951–5.
[76] Jones L, Senchyna M, Glasier MA, et al. Lysozyme and lipid deposition on silicone
hydrogel contact lens materials. Eye Contact Lens 2003;29(1 Suppl):S75–9.
[77] Senchyna M, Jones L, Louie D, May C, Forbes I, Glasier MA. Quantitative and
conformational characterization of lysozyme deposited on balafilcon and etafilcon
contact lens materials. Curr Eye Res 2004;28(1):25–36.
[78] Subbaraman LN, Bayer S, Glasier MA, Lorentz H, Senchyna M, Jones L. Rewetting
drops containing surface active agents improve the clinical performance of silicone
hydrogel contact lenses. Optom Vis Sci 2006;83(3):143–51.
[79] Boone A, Heynen M, Joyce E, Varikooty J, Jones L. Ex vivo protein deposition on
bi-weekly silicone hydrogel contact lenses. Optom Vis Sci 2009;86(11):1241–9.
[80] Metz DP, Bacon AS, Holgate S, Lightman SL. Phenotypic characterization of T cells
infiltrating the conjunctiva in chronic allergic eye disease. J Allergy Clin Immunol
1996;98(3):686–96.
[81] Greiner JV, Weidman TA, Korb DR, Allansmith MR. Histochemical analysis of
secretory vesicles in nongoblet conjunctival epithelial cells. Acta Ophthalmol
1985;63(1):89–92.
[82] Butrus SI, Ochsner KI, Abelson MB, Schwartz LB. The level of tryptase in human
tears. An indicator of activation of conjunctival mast cells. Ophthalmology
1990;97(12):1678–83.
[83] Wille H, Mølgaard IL. Giant papillary conjunctivitis in connection with cor-
neoscleral supramid (nylon) suture knots. Acta Ophthalmol 1984;62(1):75–83.
[84] Greiner JV, Covington HI, Allansmith MR. Surface morphology of giant papillary
401
The Ocular Surface 18 (2020) 396–402
conjunctivitis in contact lens wearers. Am J Ophthalmol 1978;85(2):242–52.
[85] Korb DR, Allansmith MR, Greiner JV, Henriquez AS, Richmond PP, Finnemore VM.
Prevalence of conjunctival changes in wearers of hard contact lenses. Am J
Ophthalmol 1980;90(3):336–41.
[86] Holden BA, Sankaridurg PR, Jalbert I. Adverse events and infections. In: Sweeney
DF, editor. Silicone hydrogels: the rebirth of continuous wear. Oxford: Butterworth
Press; 2000. p. 150–213.
[87] Sheldon L, Biedner B, Geltman C, Sachs U. Giant papillary conjunctivitis and ptosis
in a contact lens wearer. J Pediatr Ophthalmol Strabismus 1979;16(2):136–7.
[88] Molinari JF. Transient ptosis secondary to giant papillary conjunctivitis in a hy-
drogel lens patient. J Am Optom Assoc 1983;54(11):1007–9.
[89] Beljan J, Beljan K, Beljan Z. Complications caused by contact lens wearing. Coll
Antropol 2013;37(Suppl 1):179–87.
[90] Urgacz A, Mrukwa E, Gawlik R. Adverse events in allergy sufferers wearing contact
lenses. Postepy Dermatol Alergol 2015;32(3):204–9.
[91] Mantelli F, Lambiase A, Bonini S. Clinical trials in allergic conjunctivits: a sys-
tematic review. Allergy 2011;66(7):919–24.
[92] Kari O, Saari KM. Diagnostics and new developments in the treatment of ocular
allergies. Curr Allergy Asthma Rep 2012;12(3):232–9.
[93] Baab S, Le PH, Kinzer EE. Allergic conjunctivitis. StatPearls [Internet]. Treasure
Island (FL). StatPearls Publishing; 2020. 2019 Dec 22.
[94] Zhu H, Bandara MB, Vijay AK, Masoudi S, Wu D, Willcox MD. Importance of rub
and rinse in use of multipurpose contact lens solution. Optom Vis Sci
2011;88(8):967–72.
[95] Luensmann D, Heynen M, Liu L, Sheardown H, Jones L. The efficiency of contact
lens care regimens on protein removal from hydrogel and silicone hydrogel lenses.
Mol Vis 2010;16:79–92.
[96] Anderson DF. Management of seasonal allergic conjunctivitis (SAC): current
therapeutic strategies. Clin Exp Allergy 2001;31(6):823–6.
[97] Lim CHL, Stapleton F, Mehta JS. Review of contact lens-related complications. Eye
Contact Lens 2018;44(Suppl 2):1–10.
[98] Wingard JB, Mah FS. Critical appraisal of bepotastine in the treatment of ocular
itching associated with allergic conjunctivitis. Clin Ophthalmol 2011;5:201–7.
[99] Meisler DM, Berzins UJ, Krachmer JH, Stock EL. Cromolyn treatment of giant
papillary conjunctivitis. Arch Ophthalmol 1982;100(10):1608–10.
[100] Kruger CJ, Ehlers WH, Luistro AE, Donshik PC. Treatment of giant papillary
conjunctivitis with cromolyn sodium. CLAO J 1992;18(1):46–8.
[101] Akman A, Irkeç M, Orhan M, Erdener U. Effect of lodoxamide on tear leukotriene
levels in giant papillary conjunctivitis associated with ocular prosthesis. Ocul
Immunol Inflamm 1998;6(3):179–84.
[102] Fahy GT, Easty DL, Collum LMT, Benedict-Smith A, Hillery M, Parsons DG.
Randomised double-masked trial of lodoxamide and sodium cromoglycate in al-
lergic eye disease: a multicentre study. Eur J Ophthalmol 1992;2(3):144–9.
[103] Chigbu DI, Coyne AM. Update and clinical utility of alcaftadine ophthalmic so-
lution 0.25% in the treatment of allergic conjunctivitis. Clin Ophthalmol
2015;9:1215–25.
[104] Mahvan TD, Buckley WA, Hornecker JR. Alcaftadine for the prevention of itching
associated with allergic conjunctivitis. Ann Pharmacother 2012;46(7–8):1025–32.
[105] Horak F, Stubner P, Zieglmayer R, Kawina A, Moser M, Lanz R. Onset and duration
of action of ketotifen 0.025% and emedastine 0.05% in seasonal allergic con-
junctivitis : efficacy after repeated pollen challenges in the vienna challenge
chamber. Clin Drug Invest 2003;23(5):329–37.
[106] Asbell P, Howes J. A double-masked, placebo-controlled evaluation of the efficacy
and safety of loteprednol etabonate in the treatment of giant papillary con-
junctivitis. CLAO J 1997;23(1):31–6.
[107] Friedlaender MH, Howes J. A double-masked, placebo-controlled evaluation of the
efficacy and safety of loteprednol etabonate in the treatment of giant papillary
conjunctivitis. The Loteprednol Etabonate Giant Papillary Conjunctivitis Study
Group I. Am J Ophthalmol 1997;123(4):455–64.
[108] Khurana S, Sharma N, Agarwal T, et al. Comparison of olopatadine and fluor-
ometholone in contact lens-induced papillary conjunctivitis. Eye Contact Lens
2010;36(4):210–4.
[109] Bielory L, Friedlaender MH. Allergic conjunctivitis. Immunol Allergy Clin. North.
Am 2008;28(1):43–58.
[110] Swamy BN, Chilov M, McClellan K, Petsoglou C. Topical non-steroidal anti-in-
flammatory drugs in allergic conjunctivitis: meta-analysis of randomized trial
data. Ophthalmic Epidemiol 2007;14(5):311–9.
[111] Miraldi Utz V, Kaufman AR. Allergic eye disease. Pediatr Clin 2014;61(3):607–20.
[112] Mishra GP, Tamboli V, Jwala J, Mitra AK. Recent patents and emerging ther-
apeutics in the treatment of allergic conjunctivitis. Recent Pat Inflamm Allergy
Drug Discov 2011;5(1):26–36.
[113] Uchio E. Possibility of non‐steroidal treatment in allergic conjunctival diseases.
Allergol Int 2004;53(4):315–9.
[114] Kymionis GD, Goldman D, Ide T, Yoo SH. Tacrolimus ointment 0.03% in the eye
for treatment of giant papillary conjunctivitis. Cornea 2008;27(2):228–9.
[115] Vichyanond P, Tantimongkolsuk C, Dumrongkigchaiporn P, Jirapongsananuruk O,
Visitsunthorn N, Kosrirukvongs P. Vernal keratoconjunctivitis: result of a novel
therapy with 0.1% topical ophthalmic FK-506 ointment. J Allergy Clin Immunol
2004;113(2):355–8.
[116] Kheirkhah A, Zavareh MK, Farzbod F, Mahbod M, Behrouz MJ. Topical 0.005%
tacrolimus eye drop for refractory vernal keratoconjunctivitis. Eye
2011;25(7):872–80.
[117] Vichyanond P, Kosrirukvongs P. Use of cyclosporine A and tacrolimus in treatment
of vernal keratoconjunctivitis. Curr Allergy Asthma Rep 2013;13(3):308–14.
[118] BenEzra D, Pe'er J, Brodsky M, Cohen E. Cyclosporine eyedrops for the treatment
of severe vernal keratoconjunctivitis. Am J Ophthalmol 1986;101(3):278–82.
S.E. Kenny, et al.
[119] Secchi AG, Tognon MS, Leonardi A. Topical use of cyclosporine in the treatment of
vernal keratoconjunctivitis. Am J Ophthalmol 1990;110(6):641–5.
[120] Del Prete A, Chiosi E, Magli A, Calandriello M, Bernardo B, Bracale G. Surgical
treatment and desensitization therapy of giant papillary allergic conjunctivitis.
Ophthalmic Surg 1992;23(11):776–9.
[121] Lai Y, Sundar G, Ray M. Surgical treatment outcome of medically refractory huge
giant papillary conjunctivitis. Am J Ophthalmol Case Rep 2017;8:22–4.
[122] Allansmith MR. Pathology and treatment of giant papillary conjunctivitis. I. The
U.S. perspective. Clin Therapeut 1987;9(5):443–50.
[123] Donshik PC, Ballow M, Luistro A, Samartino L. Treatment of contact lens-induced
giant papillary conjunctivitis. CLAO J 1984;10(4):346–50.
[124] Bartlett JD, Howes JF, Ghormley NR, Amos JF, Laibovitz R, Horwitz B. Safety and
efficacy of loteprednol etabonate for treatment of papillae in contact lens-asso-
ciated giant papillary conjunctivitis. Curr Eye Res 1993;12(4):313–21.
[125] Papas EB, Ciolino JB, Jacobs D, et al. The TFOS international workshop on contact
lens discomfort: report of the management and therapy subcommittee. Invest
Ophthalmol Vis Sci 2013;54(11):183–203.
[126] Donshik PC, Porazinski AD. Giant papillary conjunctivitis in frequent-replacement
402
The Ocular Surface 18 (2020) 396–402
contact lens wearers: a retrospective study. Trans Am Ophthalmol Soc
1999;97:205–16.
[127] Cho P, Boost MV. Daily disposable lenses: the better alternative. Cont Lens
Anterior Eye 2013;36(1):4–12.
[128] Bucci FA, Lopatynsky MO, Jenkins PL, Mackay AT, Rickert DG, Gold RM.
Comparison of the clinical performance of the Acuvue disposable contact lens and
CSI lens in patients with giant papillary conjunctivitis. Am J Ophthalmol
1993;115(4):454–9.
[129] Maguen E, Rosner I, Caroline P, Macy JI, Nesburn AB. A retrospective study of
disposable extended wear lenses in 100 patients: year 2. CLAO J
1992;18(4):229–31.
[130] Lin ST, Mandell RB, Leahy CD, Newell JO. Protein accumulation on disposable
extended wear lenses. CLAO J 1991;17(1):44–50.
[131] Yeung KK, Forister JF, Forister EF, Chung MY, Han S, Weissman BA. Compliance
with soft contact lens replacement schedules and associated contact lens-related
ocular complications: the UCLA Contact Lens Study. Optometry
2010;81(11):598–607.