Looking Through The Eye: Ocular Involvement

of Autoimmune Disease
Rina La Distia Nora, MD
 There are
more than
100
autoimmune
diseases

https://www.aarda.org/diseaselist/
Possible clinical scenarios

• Patient have eye

complaints: related or
not related to the
main disease?
• Need to complete a
diagnostic criteria

• There is an eye inflammation

with possible differential
diagnosis: is there any other
organ involvement?
• Treatment collaboration and
to observe the systemic effect
Intraocular Extraocular: orbita/adnexa and ocular
surface

The possibilities of eye problems vs

100 autoimmune disease
• Organization of the eye to support its function
• Mechanism of autoimmunity in intraocular inflammation:
uveitis
• How ophthalmologist approach eye inflammation:
• Anatomical location
• Etiological classification
Highly organized and complex tissue to
for an optimal visual function!

Internal / Sensorineural Layer

Retina (Macula,Optic Nerve, Vitreous Humor)

Median / Vascular layer (Uvea)

Iris Ciliary body Choroid

External / Fibrous layer

Cornea Limbus Sclera

Caspi et al., 2010

Why the eye is an immune privileged organ?

1. True blood ocular barrier: efficient separation of the eye from the
immune system
2. Educational local gate: local inhibition responses by the unique
intraocular microenvironment
3. Educational systemic gate: systemic induction of
immunosuppressive regulatory T cells
 2. Local
educational gate:
outer blood retinal
1. True barrier: inner barrier
blood retinal barrier

2. Local
educational gate:
blood aqueous
barrier

Shechter et al., 2013

3. Systemic educational
gate: T-regulatory cells
instead of T-helper cells
 Autoimmunity mechanism?

1. Aberrant immune
recognition of self.
2. Innate inflammatory reaction
triggered by environmental microbial or
autologous tissue damage danger
signals
Caspi et al., 2010
How ophthalmologists approach eye
inflammation?
Approach in uveitis cases
Recognize anatomical location (along with ocular imaging) and
pathognomonic history, signs, and symptoms!

What is the most common cause?

Step ladder work up

Treat judiciously and collaborate!

Follow up and watch for complication.

 Umbrella term for more than 30 individual disease entities

C l a s s i f i c a t i o n : Exclude
c a u infectious
s e uveitis first!
La Distia Nora 2018, Thesis
 Indonesia, La Distia South Thailand, Germany, Jakob
Nora et al 2017 Sittivarakul et al E et al 2015,
Characteristic
(n=146) 2013 (n=254) n=1916
n (%) n (%) n (%)
Laterality
Unilateral 100 (68%) 151 (60%) --
Bilateral 46 (32%) 130 (40%) --
Anatomical location
Anterior uveitis 29 (20%) 90 (35%) 870 (45%)
Intermediate uveitis 4 (3%) 9 (3%) 434 (23%)
Anterior and Intermediate uveitis -- 17 (7%) --
Posterior uveitis 56 (38%) 50 (20%) 259 (13.5%)
Panuveitis 55 (38%) 88 (35%) 119 (6%)

What is Etiology
Infections 48 (33%) 69 (27%) 254 (13%)

the most Toxoplasmosis

Tuberculosis
30 (20%)
12 (8%)
18 (7%)
3 (2%)
80 (4%)
21 (1%)

common
Herpetic anterior uveitis (HSV, VZV) 2 (1.2%) 12 (5%) 79 (4%)
CMV anterior uveitis 1 (0.6%) 8 (3%) 8 (0.4%)
Acute retinal necrosis 2 (1.2%) 10 (4%) 10 (0.5%)

cause?
Syphillis 1 (0.6%) 7 (3%) 4 (0.2%)

Non infectious associated with systemic

11 (7.5%) 66 (26%) 495 (26%)
disease
VKH 4 (2.5%) 28 (11%) 4 (0.2%)
Behçet disease 4 (2.5%) 18 (7%) 35 (2%)
Ankylosing spondilytis -- 7 (3%) 83 (4%)
SLE 1 (0.6%) 3 (1%) 3 (1.5%)
Inflammatory bowel disease -- 2 (1%) 16 (0.8%)
Sarcoidosis 1 (0.6%) 2 (1%) 86 (4.5%)

Non infectious limited to the eye/ ocular

clinical syndromes 21 (14%) 45 (18%) 388 (20%)
HLA-B27 related -- 20 (8%) 136 (7%)
FUS 4 (2.5%) 5 (2%) 133 (7%)
SO -- 2 (1%) --

Unknown cause 66 (45%) 74 (30%) 676 (35%)

Characteristic Indonesia, La Distia Nora et al 2017 South Thailand, Sittivarakul et al 2013 Germany, Jakob E et al 2015
(n=146) (n=254) n=1916
n (%) n (%) n (%)
Anterior
Infection Herpes Herpes Herpes
Systemic disease Masquerade Ankylosing spondilytis Ankylosing spondilytis
Ocular clinical syndrome FUS HLA-B27 + anterior uveitis, FUS HLA-B27 + anterior uveitis, FUS
Intermediate
Infection -- Syphilis Toxoplasmosis
Systemic disease -- Behçet disease Multiple sclerosis
Ocular clinical syndrome Pars planitis Cogan syndrome FUS, sarcoidosis
Posterior
Infection Toxoplasmosis, TB Toxoplasmosis Toxoplasmosis
Systemic disease Behçet disease Behçet disease Behçet disease, sarcoidosis
Ocular clinical syndrome Neuroretinitis Eales disease, serpiginous choroidopathy APMPPE, serpiginous chorioretinitis
Panuveitis
Infection TB, toxoplasmosis Toxoplasmosis Toxoplasmosis
Systemic disease VKH, Behçet disease VKH, Behçet disease Behçet disease, sarcoidosis
Ocular clinical syndrome Masquerade, MCP Ocular sarcoidosis, MCP Ocular sarcoidosis, MCP

What is the most common

cause?
Recognize anatomical location
a n d p a t h o g n o m o n i c h i s t o r y,
signs, and symptoms!
Describe clinical course of uveitis
Recognize anatomical location and
pathognomonic history, signs, and symptoms!
• Cells in anterior chamber and vitreous
• Characteristics
• Quantification +0.5 up to +4
• Keratic precipitate’s characteristic
• Presence of iris nodules and synechiae
• Differentiate retinal and choroidal involvement
• Recognize the presence of vaculitis
Cells
 Medium
sized
Fine pigmented KPs KPs
Look for iris atrophy, high
IOP
Iris
nodules

occluded
pupil
Iris atrophy
look for fine pigmented
KPs, high IOP
Broad based posterior
synechiae: TB Filiform
posterior synechiae

Gupta et al 2010
No posterior synechiae!

Look for white cataract and small

iris nodules: FUS
Other intraocular and extraocular
signs and symptoms in autoimmune
diseases
 Optic Neuritis
Uveitis Keratitis

(Pupil) Keratokonjungtivitis Sicca

(Iris)
(Conjunctiva)
Scleritis (Sclera)
(Limbus)

Episcleritis
Exophthalmos
Andrade et al., 2016
 Keratitis
Symptoms
Interstitial keratitis in psoriasis and RA patient
• Red eye, Pain with photophobia, foreign body sensation,
tearing, eye, decreased vision/blurred

Signs
• Inflammatory cell infiltrate, corneal corneal ulceration,
corneal ulceration Interstitial keratitis in SLE patient

Autoimmune diseases
• Rheumatoid arthritis, Wegener granulomatosis

Peripheral ulcerative keratitis on ANCA-associated vasculitis

(Generali, Cantarini and Selmi, 2015; Patel and Diane, 2020; Levitt et al, 2015)
 Keratoconjunctivitis Sicca
Symptoms
• Dry eye, burning, pain, blurred vision, pruritus, foreign-
body sensation, mucous threads, and crusting about the
eyelids
Signs
• Diminished corneal tear meniscus, abnormal Schirmer’s
test

Autoimmune diseases
Severe tear deficiency of a patient with Sjögren syndrome
• Rheumatoid arthritis, Sjögren’s Syndrome, SLE who presented with sterile corneal melt and perforation.

(Generali, Cantarini and Selmi, 2015; Patel and Diane, 2020; Akpek et al 2019)
 Schematic view of an anterior portion of the eye and
tear film layers

The Schirmer’s test is used to assess

the function of the lacrimal glands.

Andrade et al., 2016

 Scleritis
Symptoms
• Gradual onset; deep pain may radiate into cheek eyebrows,
and temples; blurred vision; photophobia

Signs Scleritis in RA
Engorged scleral vessels do not blanch with
• Decreased visual acuity; bluish appearance with engorged application of topical phenylephrine 2.5 %
blood vessels; may have immovable, tender nodules over
the sclera, general tenderness on palpation; engorged blood
vessels do not blanch with phenylephrine
Autoimmune diseases
• Rheumatoid arthritis, Wegener granulomatosis

(Generali, Cantarini and Selmi, 2015; Patel and Diane, 2020)

 Episcleritis
Symptoms
• Sudden onset; mild ache may radiate into cheek,
eyebrows, and temples; no blurred vision; photophobia Bright red appearance.
Blanching of the vessels occurs with application
of topical phenylephrine 2.5 %
Signs
• No change in visual acuity; bright red appearance with
engorged blood vessels; may have movable, nontender
nodules over the episclera;; engorged blood vessels
blanch with phenylephrine, no tenderness on palpation
Autoimmune diseases
• Rheumatoid arthritis, Wegener granulomatosis,
polyarteritis nodosa Extensive episcleritis with dilated blood vessels
at the temporal region in an RA patient
(Generali, Cantarini and Selmi, 2015; Patel and Diane, 2020)
 Exophthalmos
Symptoms
• Irritable and gritty eyes, double or blurred vision,
photophobia, increased tearing, orbital pressure Widened palpebral fissure

Signs (Generali, Cantarini and Selmi, 2015; Patel and Diane, 2020)

• Protruding globe, widened palpebra fissures, conjunctival

injection and chemosis, lid lag and retraction, exposure
keratitis

Autoimmune diseases
• Thyroid Ophthalmopathy (Grave’s Disease)
Soft tissue involvement

(Generali, Cantarini and Selmi, 2015; Patel and Diane, 2020)

Step ladder work up
Treat judiciously and collaborate!
• Suppress inflammation
• Reduce pain and photophobia
• Prevent further damage to the eye structure
• Rehabilitate visual function
• Prevent permanent visual loss
• Limit the medication side effect
• Prevent recurrences
• Induce remission
Treat judiciously and collaborate!
• Mainstay treatment: anti inflammatory agents (steroid)
• Absolute indication for steroid sparing agents/ immunosuppressive
treatment (IMT) : e.g. Behçet disease, sympathetic ophthalmia
• Exclude infection, give appropriate anti microbe.
• Decide whether to give the steroid concurrently or after the antimicrobe
• Know when:
• Not to be aggressive and it is OK to have some cells left. E.g. Intermediate
uveitis
• Aggressive: no cells policy! E.g. Behçet disease, JIA
Foster et al, 2015
Complication in uveitis
• Glaucoma
• Cataract
• Hypotonic eye
• Retinal detachment
• CME
• Visual field defect
 CONCLUSION
• The eye is a highly organized and complex structure to support its optimal
visual function

• The eyes are frequently involved in autoimmune diseases and may offer a
diagnostic clue through identifying the anatomical involvement, thus
collaboration among specialists is essential.

• With appropriate screening, comprehensive examination and laboratory

evaluation, autoimmune disease can be identified and treated to prevent
further ophthalmic, neurologic and systemic morbidity
 Acknowledgement
• Prof. Dr. dr. Ratna Sitompul, SpM(K)
• Dr. dr. Made Susiyanti, SpM(K)
• Dr. dr. Lukman Edwar, SpM(K)
• dr. Yulia Aziza, SpM(K)
• Mei Riasanti, Ssi
• dr. Nihal Sofyan

rina.ladistia@ui.ac.id