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Sutasinee Boonsopon, M.D.*, Swetha Dhanireddy, M.D.**, Ambika Manhapra, BA.**,***, C. Stephen Foster,
M.D.**,***,****
*Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, ailand, **Massachusetts Eye Research
and Surgery Institution, Waltham, MA, USA, ***Ocular Immunology and Uveitis Foundation, Waltham, MA, USA, ****Harvard Medical School,
Department of Ophthalmology, Boston, MA, USA.
Ocular Manifestations in Rheumatoid Arthritis
ABSTRACT
Rheumatoid arthritis (RA) is an inammatory rheumatic disease that generally damages synovial-line joints.
Extra-articular manifestations of RA have been reported in cases of multiorgan involvement. ese manifestations
can occur in the hematologic and cardiovascular system, lungs, kidneys, and eyes. Various ocular manifestations of
RA have been previously reported including keratoconjunctivitis sicca, conjunctivitis, uveitis, scleritis, retinal vascular
occlusion, optic neuritis, and amaurosis fugax. It is important to recognize these ocular issues as manifestations of
RA since they can sometimes be a response marker for the onset of an immune reactivation. Urgent management
of ocular complications is essential to manage sight-threatening complications and prevent further damage to the
eyes.
Keywords: Rheumatoid arthritis; connective tissue disease; autoimmune disease; ocular manifestations; eye
involvement (Siriraj Med J 2022; 74: 340-349)
Corresponding author: C. Stephen Foster
E-mail: sfoster@mersi.com
Received 27 January 2021 Revised 6 March 2022 Accepted 11 March 2022
ORCID ID: https://orcid.org/0000-0002-6612-5653
http://dx.doi.org/10.33192/Smj.2022.41
All material is licensed under terms of
the Creative Commons Attribution 4.0
International (CC-BY-NC-ND 4.0)
license unless otherwise stated.
List of abbreviations
AION; anterior ischemic optic neuropathy
C; complement
CCP; cyclic citrullinated peptide
CD; cluster of dierentiation
DMARDs; disease-modifying antirheumatic drugs
FDA; Food and Drug Administration
HLA; human leukocyte antigen
Ig; immunoglobulin
IL; interleukin
JIA; juvenile idiopathic arthritis
KCS; keratoconjunctivitis sicca
MMP; matrix metalloproteinases
MTX; methotrexate
NSAIDs; non-steroidal anti-inammatory drugs
PUK; peripheral ulcerative keratitis
RA; rheumatoid arthritis
RF; rheumatoid factor
SMIs; small molecule inhibitors
SS; SjÖgren’s syndrome
TNF-
α; tumor necrosis factor-alpha
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Rheumatoid arthritis (RA)
Introduction of ocular manifestation of rheumatoid
arthritis
Origin/history of the ocular manifestation of
rheumatoid arthritis
Rheumatoid arthritis (RA) is a chronic progressive
autoimmune disease characterized by polyarticular synovitis.
Ocular complications, which are caused by inammatory
mediators such as immune complex depositions and
upregulation of pro-inammatory cytokines such as
tumor necrosis factor-α (TNF-α) and interleukin (IL)
6, are commonly associated with dry eye, peripheral
ulcerative keratitis (PUK), and scleritis.
1-3
Epidemiology
RA is reported to be the most common systemic
autoimmune disease. It aects roughly 1% of the general
population.
4
Previously, extra-articular manifestations of
RA were believed to occur in the late stages of the disease,
following joint inammation
5
, but we now know that
extra-articular complications can present at any stage of
the disease.
3
Extra-articular manifestations oen present
as hematologic and cardiovascular complications, while
ocular complications are less common.
3
Pathophysiology
TNF-α, IL-1, and IL-6, as proinammatory cytokines,
are believed to be involved in the inammatory pathway.
3
Prada J et al. investigated specic gene probes for TNF-α
and IL-6 from paraffin corneal sections from seven
patients who had corneal ulcerations/perforations with
RA. e results revealed TNF-α expression in 71% and
IL-6 expression in 100% of the analysed tissue samples.
6
Unfortunately, there was no control group in their study.
e authors concluded that collagenolytic corneal damage
was caused by the production of metalloproteinases as
a result of the upregulation of the proinammatory
cytokines. RA patients who presented with necrotizing
scleritis and/or PUK were involved in one of our studies.
Conjunctival and/or scleral biopsy samples revealed
microangiopathy with brinoid necrosis, vessel invasion
by neutrophils, and/or vascular immunodeposits with
immunoglobulin (Ig) A, IgG, IgM, complement (C) 3
and C4 in all patients with PUK and in 83% of patients
with necrotizing scleritis.
7
Moreover, RA patients who
experienced dry eye were found to have high levels of IL-17
in their tears.
8
A prospective case-control study among 72
RA patients revealed that there was no correlation between
joint activity and the severity of keratoconjunctivitis
sicca (KCS) symptoms.
9
Ocular manifestation of RA (Table 1)
Denition/criteria for diagnosis
Secondary SjÖgren’s syndrome (SS) and KCS
RA is one of the most common autoimmune
disorders associated with KCS.
10
Lymphocytic inltration
and destruction of acini in the lacrimal glands results
in secondary SS.
10
is lymphocyte inltration from
pathological sections of lacrimal glands obtained from
patients with primary SS and secondary SS cannot be
distinguished. e severity of dry eye symptoms and
corneal uorescein dye staining were similar in both
primary SS and secondary SS. ese features suggest
autoimmune mechanisms as a cause of dry eye, which is
fairly common in many systemic autoimmune diseases.
10
Pathophysiology
Lymphocyte and plasma cell inltration is generally
found in the tubuloacinar glands of lacrimal gland
lobules.
11-13
Symptoms and signs
e most common clinical presentation of secondary
SS is dry eye. In addition, patients may also experience
redness, light sensitivity, ocular burning sensation, foreign
body sensation, and painful supercial keratitis. Punctate
erosion, which can be detected through uorescein, rose
bengal, or lissamine green staining, is also common.
Moreover, some patients can present with visual deciencies,
corneal epitheliopathy, lament keratopathy, and plaque
formation. Diagnosis of secondary SS can also be conrmed
through objective measures such as a decrease in lacrimal
secretion (hyposecretion) through Schirmer’s test and
a decrease in lacrimal stability, measured by a decrease
in tear break-up time.
14,15
Episcleritis
Episcleritis is the inammation of episcleral tissue
over the sclera. e frequency of episcleritis in RA patients
was reported to be 0.17-3.7%.
16
Pathophysiology
Increased inammation associated with RA can lead
to the inltration of white blood cells to the episcleral
tissue and result in episcleritis. is causes the anterior
ciliary arteries to become congested and more prominent.
In addition, the dysregulation of levels of cytokines
such as transforming growth factor b in tear uid and
the subsequent loss in tear integrity are believed to be
related to episcleritis.
14
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TABLE 1. Comparison of mean number of decayed teeth by CFUs within groups.
Ocular manifestations Frequency among RA individuals References
Keratoconjunctivitis sicca 18-90% 14
Episcleritis 1-5% 14
Scleritis 1-6% 14
Anterior uveitis 14-42% 14
Peripheral ulcerative keratitis 1-2% 44
Retinal vasculitis 18% (subclinical) 36
Choroiditis rare
Optic neuropathy rare
Abbreviations: RA; rheumatoid arthritis
Symptoms and signs
Episcleritis patients generally present with red eyes
as a result of vasodilation of supercial radial episcleral
vessels, which can be sectoral, diuse, or nodular. Bilateral
involvement was found in 40% of episcleritis cases.
16
e disease itself is painless and visual loss has not been
reported. In order to dierentiate between episcleritis
and scleritis, 10% phenylephrine drops can be instilled
to assess if the characteristic constricting and blanching
of episcleral vessels associated with episcleritis occurs.
14
Scleritis
e most common systemic association with scleritis
that has been reported is RA.
17,18
About one-h to one-
fourth of patients with scleritis have RA and conversely,
0.2-6.3% of RA patients suer from scleritis.
19
Most RA
patients develop articular manifestations preceding the
onset of scleritis. Necrotizing scleritis, which is the most
severe form of scleritis, is caused by vascular occlusion
of the aected area, shown in Fig 1. Associated uveitis
and peripheral ulcerative keratitis may be associated with
scleral inammation. Complicated cataract and secondary
glaucoma are frequently found in patients with scleritis,
especially in those patients with severely inamed eyes.
17
On the other hand, patients can also develop anterior
scleritis without inammation, known as scleromalacia
perforans (Fig 2). inning of the sclera and visible uveal
tissue gradually develops as a late complication of the
inammatory processes; however spontaneous perforation
is rare. Posterior scleritis can also be associated with RA.
In these cases, subretinal uid, macular edema, papillitis,
Fig 1. Necrotizing scleritis with associated peripheral ulcerative
keratitis in rheumatoid arthritis patient.
Fig 2. Scleral thinning with exposure of the choroid covered by
healthy conjunctiva without inammation, which is also known as
scleromalacia perforans.
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or uveal inammation can result in the deterioration of
vision (Fig 3). RA-associated scleritis is typically classied
as a condition of intermediate severity.
20
Fig 3. Fundus uorescein angiogram of rheumatoid arthritis patient
who had posterior uveitis with papillitis, retinal vasculitis and cystoid
macular edema in the right eye.
Pathophysiology
Histopathological examination of scleral tissue of
patients with scleritis has shown brinoid necrosis and
vascular inltration, specically inltration of macrophages
and T-lymphocytes. ese ndings are similar to what
is found in patients with occlusive retinal vasculitis.
21,22
Furthermore, collagenase matrix metalloproteinase-3
(MMP-3), MMP-8, and MMP-9 are speculated to be
responsible for collagen breakdown, in combination
with the imbalance of MMP and tissue inhibitors of
MMPs.
14,23
Symptoms and signs
Severe eye pain is the main symptom of scleritis.
Bilateral involvement was found in half of cases.
24
Redness
(deep violaceous hue) with scleral edema and dilation
of the supercial and deep episcleral vascular plexuses
are important signs of scleritis. Tearing, photophobia,
and decreased visual acuity can also be found.
14
Classication regarding anatomical location
The location of inflammation compared to the
insertion of the rectus muscles is used to classify scleritis
to either anterior scleritis and posterior scleritis. Anterior
scleritis is more commonly found compared to posterior
scleritis.
15,16
e diagnosis of posterior scleritis is more
challenging. Ocular examination in the early stages of
inammation may sometimes show no abnormalities,
while more severe cases may reveal optic disc swelling,
retinal fold, retinal exudates, subretinal uid and macular
edema.
15
Ocular pain is an important feature that should
alert the physician to assess if scleritis is present. Blurred
vision is commonly associated with scleritis, as a result
of refractive shi from thickened posterior sclera or
from the inammatory processes itself. Patients may
experience metamorphopsia from macular fold and
macular edema.
25
B-scan ultrasonography is the most
useful diagnostic tool, which conrms the diagnosis of
posterior scleritis by showing scleral thickening and
demonstrating any scleral nodules, if present.
26
(Fig 4)
Fig 4. B-scan ultrasonography of the right eye shows chorioretinal
thickening with classicT-sign, which represent subtenon uid in
patient with posterior scleritis.
Classification regarding the pattern of scleral
inammation
Scleritis can be classified into diffuse scleritis,
nodular scleritis and necrotizing scleritis with or without
inflammation. Diffuse anterior scleritis is the most
common type of RA associated scleritis, followed by
nodular anterior, necrotizing, and posterior scleritis.
27
Diuse scleritis is more benign than other types of scleral
inammation.
28
Necrotizing scleritis with inammation
is a type of inammation that increases the probability
of other ocular complications such as marginal keratitis,
anterior uveitis, and secondary ocular hypertension, and
disease associations include connective tissue diseases and
vasculitic diseases with infectious diseases, rosacea, and
foreign body.
16
Scleromalacia perforans is characterized
by the bluish-grey hue of the sclera without any sign of
inammation. It was believed to be a result of scleral
thinning.
25
Peripheral ulcerative keratitis
PUK is relatively common in patients with connective
tissue diseases, especially among RA patients.
17
PUK can
lead to corneal melt syndrome and ocular perforation, and
may be associated with scleritis.
17
Corneal perforation is
the most severe ocular complication in RA patients.
24
We
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344
reported the mortality rate of RA patients’ concurrence
with PUK and/or necrotizing scleritis was approximately
50% at 10 years without immunosuppressive medication.
e major cause of death in that study was rheumatoid
vasculitis.
29
When PUK is found in RA patients, urgent
multidisciplinary management is required.
24
Pathophysiology
Both cellular and humoral immunity are involved
in the inammation process. T- and B-lymphocytes play
an important role in increasing antibody production
and immune-complex deposition around the peripheral
cornea.
30, 31
Inammatory cells, specically neutrophils and
macrophages, are recruited to the cornea by C activation.
24
Collagenases and other proteases, secreted from those
inammatory cells, cause corneal melting and eventually
perforation.
32
Abnormal MMP-2 production and the
presence of MMP-9
33,34
, and possibly other MMPs have
been thought to be related to PUK progression.
Symptoms and signs
Symptoms and signs of PUK include ocular pain
and redness, photophobia, tearing, visual deterioration
from corneal astigmatism or corneal opacity, peripheral
corneal thinning, and ulceration
15
(Fig 5).
longstanding rheumatoid factor (RF) positive cases.
37
Circulating immune complex, co-stimulatory molecule
(CD28) on naive T cells, and proinammatory cytokines
are involved in the inammatory processes.
38
Intraocular
inammation, more specically retinal vasculitis (despite
its rare presentation), PUK and necrotizing scleritis, is
considered as a clinical manifestation of rheumatoid
vasculitis.
36,39
Symptoms and signs
Most RA patients with retinal vasculitis are
asymptomatic and show no clinical signs of retinal
vasculitis. However subclinical retinal vasculitis with
retinal vascular leakage on fundus uorescein angiogram
has been reported in 18% of RA patients.
40
Optic neuritis and anterior ischemic optic neuropathy
(AION)
Optic neuritis and AION occur at a lower frequency
compared to PUK, corneal melt, and scleritis.
10
Optic
disc swelling can occur secondary to posterior scleritis.
17
Risk factors
Predisposing genetic factors such as the human
leukocyte antigen (HLA)-DR4 allele, and inappropriate
immune mechanisms leading to immune complex deposition
and microvasculitis in the joint play a pivotal role in the
pathogenesis and joint destruction of RA.
7
High titers of
RF, circulating immune complexes, cryoglobulinemia
and hypocomplementemia are strongly associated with
rheumatoid systemic vasculitis.
41
ese laboratory parameters
also have been abnormal in a high percentage of patients
with RA who developed necrotizing scleritis and/or PUK,
observed in our study.
7
Patients who were both anticyclic
citrullinated peptide (anti-CCP) and RF positive tend
to have more severe ocular disease.
42-44
Treatment
Indications for treatment
Most RA patients have dry eye symptoms, which
is generally mild to moderate in severity. Treatment for
these patients comprise of lubricating eye drops, and in
some instances, topical cyclosporine eye drops.
24
e use
of autologous serum tear drops is typically reserved for
more severe cases of dry eye.
45
Systemic medications
such as doxycycline can inhibit MMP and induce T
cell apoptosis, which is also useful in decreasing the
inammatory cascade associated with dry eye syndrome.
46,47
For the more severe cases of dry eye, such as dry eye
with corneal epitheliopathy, scleritis, and PUK, the
previously mentioned therapy is generally inadequate
Fig 5. Anterior segment photograph showing an extensive area of
peripheral corneal thinning with abnormal feeding vessel in a patient
with peripheral ulcerative keratitis associated with rheumatoid
arthritis.
Retinal vasculitis
Retinal vasculitis, which describes inammation of
retinal blood vessels can result in poor visual outcome
35
and is associated with several connective tissue diseases,
including RA.
36
Pathophysiology
Rheumatoid vasculitis is believed to be related to
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to control the disease
10
(Fig 5). Almost every type of
scleritis eventually requires systemic therapy such as
non-steroidal anti-inammatory drugs (NSAIDs) and
corticosteroids.
28
Immunomodulatory therapy is indicated
in PUK or scleritis patients who fail to respond to oral
corticosteroid therapy. erapy failure is dened as
having persistent inammation, disease progression,
intolerability to corticosteroid side eects, or unable to
taper prednisolone to physiologic doses.
27
e treatment
modalities for ocular manifestations in RA is summarized
in Table 2.
Medical treatment
Non-steroidal anti-inammatory medications
Oral NSAIDs are considered useful in mild forms
of scleritis.
25
ey can be used as a rst-line therapy for
patients with non-necrotizing scleritis.
48
Necrotizing
scleritis, which is the more severe form of scleritis, and
posterior scleritis, where the inammatory site located
at the back of the eye, require systemic corticosteroid
therapy, and eventually immunomodulatory therapy.
25
Corticosteroids
Initial treatment that is eective at controlling active
inammation is high doses of systemic corticosteroids. For
the more severe cases such as necrotizing scleritis or PUK
with impending corneal perforation, methylprednisolone
infusion is recommended. During maintenance therapy, slow
taper of the medication is required. Relapsed inammation
can oen occur during the tapering of medication.
25,49
Topical steroids can be used as an adjunctive treatment
for scleritis with anterior uveitis.
25
Immunosuppressant medications
About ¼ of scleritis patients require immunomodulatory
therapy to control their inammation.
19
In RA associated
scleritis, the indication for immunosuppressants is broad.
7
Antimetabolite
Methotrexate (MTX) has proved to be highly
benecial.
7
MTX has less potential toxicity compared to
cytotoxic agents and is used as a rst-line medication in the
chemotherapeutic management of PUK and necrotizing
scleritis in most patients with RA. Azathioprine is a second-
line medication for chemotherapeutic management in
RA.
7
Calcineurin inhibitor
Cyclosporine is a second line drug, which may be
successful in select cases.
31
Cytotoxic agent
Chlorambucil has been used as a treatment option for
RA, but its ecacy related to extra-articular manifestation
is rarely reported. Cyclophosphamide has been the most
eective, but
7
is associated with higher toxicity.
Biologic agents
Biologic agents are usually reserved for the treatment
of RA that is refractory to conventional therapy. ey
have a favorable safety prole as compared to cytotoxic
agents but their use must be closely monitored to avoid the
reactivation of latent infections such as mycobacterium
tuberculosis and to avoid the risk of opportunistic
infections.
44,50
TNF inhibitors
TNF inhibitors that are approved by the U.S. Food
and Drug Administration (FDA) for the treatment of
RA are etanercept (Enbrel®), iniximab (Remicade®),
adalimumab (Humira®)
3
, certolizumab pegol (Cimzia®)
and golimumab (Simponi®).
51
TNF inhibitors can decrease
inammation and corneal destruction by decreasing
the products of MMP, such as MMP-9, which halts the
destruction of corneal epithelial basement membrane
and the degradation of extracellular matrix of the
corneal stroma.
34,52,53
MTX may have synergistic eects
when combined with TNF inhibitors.
54
Etanercept and
adalimumab were also reportedly successful in select
cases.
55,56
Iniximab is the more favorable treatment
option, especially in uveitis, because of its successful
outcomes.
57,58
On the other hand, some reports suggested
that etanercept may induce intractable scleritis or is
ineective in treating scleritis.
59,60
Certolizumab pegol,
a newer TNF-α inhibitor, has been used to treat extra-
articular manifestations of RA, but very few reports have
been published on this medication.
61
is medication
diers from the older TNF-α inhibitors in that it has a
longer half-life with less toxicity.
62
e use of golimumab in
several case reports and case series demonstrate successful
control of recalcitrant uveitis associated with juvenile
idiopathic arthritis (JIA), Adamantiades-Behçet’s disease,
idiopathic retinal vasculitis, spondyloarthropathies, and
HLA-B27 positivity.
63-67
IL-1 inhibitor
Anakinra (Kineret®) is approved by the FDA.
3
In scleritis, both TNF-α and IL-1 released by the local
inammatory cell inltrate have been associated with
scleral destruction.
68
An observation by C. Botsios et al.
demonstrates the ecacy of anakinra in RA associated
diuse scleritis.
69
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TABLE 2. Treatment modalities for ocular complications in rheumatoid arthritis.
Medications Route of administrations Indications Evidence
Articial tears ED KCS
Autologous serum ED KCS
Topical cyclosporine ED KCS
Doxycycline Oral KCS
NSAIDs ED/ oral Episcleritis/ scleritis (mild form)
Corticosteroids ED/ oral/ IV Episcleritis/ scleritis/ PUK/ uveitis
Immunosuppressant
Antimetabolite
Methotrexate Oral/ SC Scleritis/ PUK/ uveitis First line
Scleritis/ PUK/ uveitis
Azathioprine Oral Second line
Mycophenolate mofetil Oral Scleritis/ PUK/ uveitis -
Calcineurin inhibitor
Cyclosporine Oral Scleritis/ PUK/ uveitis Second line
Cytotoxic agents
Cyclophosphamide Oral/ IV Scleritis/ PUK/ uveitis Recommended in
severe and/ or
refractory cases
Chlorambucil Oral Uveitis -
Biologic agents
TNF inhibitors
Iniximab IV Scleritis/ PUK/ uveitis RCT
Adalimumab SC Scleritis/ PUK/ uveitis FDA-approved
Certolizumab pegol SC Uveitis Case reports
Golimumab SC Uveitis Case reports
Etanercept SC Not recommended (less effective) Phase II/III
IL-inhibitors
Anakinra SC Scleritis Case reports
Tocilizumab SC/ IV Scleritis/ PUK/ uveitis Case reports
Gevokizumab SC Scleritis Phase I/II
B-cell depletion
Rituximab IV Scleritis/ PUK/ uveitis Phase I/II
Cytotoxic T-lymphocyte antigen 4
Abatacept SC/ IV Scleritis/ uveitis Case reports
Small molecules inhibitors
Janus kinase
Tofacitinib Oral Scleritis/ uveitis Phase II
Baricitinib Oral Uveitis Case reports
Filgotinib Oral NA NA
Pecitinib Oral NA NA
Decernotinib Oral NA NA
Other new medications
ACTH gel SC Scleritis Phase II
Sirolimus Subconjunctival Scleritis Case reports
Abbreviations: ED; eye drops, KCS; keratoconjunctivitis sicca, NSAIDs; non-steroidal anti-inammatory drugs, IV; intravenous, PUK;
peripheral ulcerative keratitis, SC; subcutaneous, TNF; tumor necrosis factor, RCT; randomized controlled trial, FDA; food and drug
administration, IL; interleukin, NA; not applicable, ACTH; adrenocorticotropic hormone
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IL-6 inhibitor
Tocilizumab (Actemraâ) is approved for the treatment
of RA and JIA.
70
Successful suppression of PUK in RA
patient with tocilizumab has been reported.
71
B-cell depletion
Rituximab (Rituxanâ) is a chimeric monoclonal
antibody against cluster of dierentiation (CD) 20 aimed
at depleting B cells. It is reported as a successful treatment
for many connective tissue diseases, including RA. T-cell
activation in scleritis and PUK might be associated with
the existence of B lymphocytes surrounding blood vessels,
resulting in immediate action of rituximab.
72,73
Cytotoxic T-lymphocyte antigen 4 (CTLA 4)
Abatacept (Orenciaâ) is a recent yet widely utilized
therapeutic option in RA.
74
Its ecacy to treat extra-
articular manifestations is under investigation. One
patient developed PUK while on abatacept, and the
treatment was switched to tofacitinib citrate (Xeljanzâ)
combined with corneal gluing within one week, which
led to a successful treatment of the PUK.
75
Several reports
demonstrated its ecacy to control or improve refractory
JIA related uveitis.
76-79
Surgical treatment
Surgical indication for scleritis and PUK is
corneoscleral melting with impending perforation or
perforation, both of which require immediate surgical
intervention. Surgery can also be used as an adjunctive
treatment to decrease or halt the progression of active
inammation in some instances.
25
Surgical interventions
include cyanoacrylate adhesive, tectonic corneal gra,
conjunctival flap, and scleral grafting. Conjunctival
resection may also be done to enhance the healing process
of PUK by decreasing the number of inammatory cells
and cytokines surrounding the cornea and thus, promoting
corneal epithelialization.
7,80
A combination treatment of
immunomodulatory medication and adjuvant surgical
intervention can generally preserve the eyeball in most
of the RA patients, but visual outcome is sometimes
unsatised.
7
Future direction
Recently, there has been development of small
molecule inhibitors (SMIs) for RA as a new generation
of targeted synthetic disease-modifying antirheumatic
drugs (DMARDs). ese medications can block pro-
inammatory pathways such as Janus kinase, mitogen-
activated protein kinase, and spleen tyrosine kinase.
81
e
therapeutic treatment of SMIs for ocular manifestations
related to RA is yet to be investigated.
44
ACKNOWLEDGEMENTS
None
Funding disclosure
is was an unfunded study.
Conict of interest
S Boonsopon, S Dhanireddy and A Manhapra
report no conict of interest. C. Stephen Foster reports
no conict of interest, but declares consultancies with
Aldeyra erapeutics, Allakos, Bausch & Lomb Surgical,
Inc, Eyegate Pharma, Genentech, Novartis, pSivida;
grants or grants pending with Aciont, Alcon, Aldeyra
erapeutics, Bausch & Lomb, Clearside Biomedica,
Dompé pharmaceutical, Eyegate Pharma, Mallinckrodt
pharmaceuticals, Novartis Pharmaceuticals, pSivida,
Santen; payment for lectures including service on speaking
bureaus: Alcon, Allergan, Mallinckrodt pharmaceuticals;
stock or stock options: Eyegate Pharma.
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