Connective tissue diseases can involve the eyes and cause various inflammatory conditions. Rheumatoid arthritis is a common cause of scleritis and episcleritis, occurring in 4-10% of patients. Keratoconjunctivitis sicca (dry eyes) is the most common ocular manifestation of rheumatoid arthritis, affecting 10-35% of patients, mostly women. Scleritis may occur and can cause vision loss if not treated adequately with immunosuppressants. Keratitis can also occur from corneal thinning or ulceration. Systemic lupus erythematosus can also cause ocular inflammation and is more common in women.

1. Eye Manifestations In Connective Tissue
Disorders
Dr. Amar Patil
PG Medicine

2. Introduction
Connective tissue disease refers to a group of disorders involving the
protein-rich tissue that supports organs and other parts of the body.
Examples of connective tissue are fat, bone, and cartilage. These
disorders often involve the joints, muscles, and skin, but they can also
involve other organs and organ systems, including the eyes, heart,
lungs, kidneys, gastrointestinal tract, and blood vessels.

3. • Many connective tissue diseases have abnormal immune system
activity with inflammation in tissues as a result of an immune system
that is directed against one’s own body tissues (autoimmunity).
• Ocular inflammation is seen as part of a number of systemic diseases
with autoimmune processes heading the list. Inflammation can affect
any part of the eye starting from the cornea anteriorly to the retina,
uveal tract and sclera posteriorly.
• In some conditions, uveitis or scleritis is the heralding presentation
and in others it determines the need for more aggressive
immunosuppressive therapy.

4. • The incidence, severity, and disease course of uveitis and scleritis are
variable with many factors contributing to the natural history of the
disease, including gender, the underlying systemic disease, and the
extent of the inflammatory process.

5. Anatomy of Eye

6. Sclera
• Sclera forms the posterior 5/6th of the opaque part of the external
fibrous tunic of the eyeball. In the anterior part it is covered by bulbar
conjunctiva.
• Histologically sclera consists of 3 layers: ( image)
i)Episcleral tissue – it is a thin dense vascularised layer of connective
tissue which covers the sclera proper.
ii) Sclera proper – it is an avascular structure which consists of dense
bundles of collagen fibres. The branch of collagen tissue cross each other
in all directions.

7. • iii) Lamina fusca – it is inner most part of sclera which blends with
supra choroidal and supra ciliary laminae of the uveal tract.

8. Episcleritis
• It is benign inflammation of the episclera involving the overlying
tenons capsule but not the underlying sclera.
• Types :
i. Simple episcleritis
ii. Nodular episcleritis
• Symptoms and Signs: Redness and ocular discomfort described as
gritty or burning sensation. Rarely mild photophobia and lacrimation
can occur

9. • Treatment :
i. Topical artifical tears: 0.5% carboxy methyl cellulose
ii. Topical NSAIDs: keratolac 0.3%
iii. Topical mild corticosteroid eye drops: fluorometholone.
iv. Cold compresses
v. Systemic NSAIDs: indomethacin (25mg three times a day)

10. Scleritis
• Scleritis refers to a chronic inflammation of the sclera proper.
• It is a comparatively serious disease which may cause visual
impairment and even loss of the eye if treated inadequately.
• Its incidence is much less than that of episcleritis. It usually occurs in
elderly patients (40-70 years) involving females more than the males.

11. Etiology :
• Autoimmune collagen disorders : Rheumatoid arthritis, is the most
common association. Overall about 5% cases of scleritis
• Metabolic disorders like gout and thyrotoxicosis have also been
reported to be associated with scleritis.
• Infections : Herpes zoster ophthalmicus, chronic staphylococcal and
streptococcal infection.
• Granulomatous diseases: Tuberculosis, syphilis, sarcoidosis, leprosy
can also cause scleritis.
• Miscellaneous conditions like irradiation, chemical burns, behcet's
disease and rosacea are also implicated

12. Symptoms:
• Patients complain of moderate to severe pain which is deep and
boring in character and often wakes the patient early in the morning .
• Ocular pain radiates to the jaw and temple. It is associated with
localised or diffuse redness, mild to severe photophobia and
lacrimation.
• Occasionally there occurs diminution of vision.

13. • Types
i. Non-necrotizing anterior diffuse scleritis
ii. Non-necrotizing anterior nodular scleritis
iii. Anterior necrotizing scleritis with inflammation
iv. Anterior necrotizing scleritis without inflammation (scleromalacia
perforans)
v. Posterior scleritis

14. Treatment:
• Non-necrotising scleritis - It is treated by topical steroid eyedrops and
systemic indomethacin 100 mg daily for a day and then 75 mg daily
until inflammation resolves.
• Necrotising scleritis - It is treated by topical steroids and heavy doses
of oral steroids tapered slowly. In non-responsive cases, immuno-
suppressive agents like methotrexate or cyclophosphamide may be
required.

15. • To distinguish from episcleritis and scleritis phenylephrine 2.5% eye
drops is used. The instillation of one or two drops in the affected eye
will constrict the superficial episcleral vessels but not the deeper
scleral vessels .

16. Rheumatoid Arthritis
• Rheumatoid arthritis is a chronic inflammatory disease of unknown
etiology marked by symmetric ,peripheral polyarthritis.
• Ocular manifestations of this autoimmune disease vary and are mainly
i) Keratoconjunctivitis sicca
ii) Episcleritis
iii) Scleritis
iv) Keratitis
v) Uveitis
vi) Scleromalacia perforans.(Necrotising scleritis)
Their appearance, as well as their severity are related to RA chronicity and
resistance to therapy

17. Keratoconjunctivitis sicca (Dry eye syndrome)
• It is the most common eye sign of RA with a percentage of 10% - 35%.
• Dry eye can be either “aqueous deficient ” or “evaporative” type.
• Gender plays a key role with 90% of the patients being females
• Pathology:
i) It is caused by infiltration of the lacrimal gland by T and B lymphocytes,
leading to a secondary atrophy of the gland which is responsible for the
decrease of tears.
ii) Females with primary Sjogren’s syndrome (without any underlying
autoimmune problem) have elevated levels of antinuclear antibody(ANA)and
autoantibodies directed against Ro/SSA and La/SSB autoantigens. This is
thought to be secondary to higher estrogen levels in women, which, being
immune stimulatory, result in accelerated humoral and cell mediated
response

18. iii) The evaporative type of dry eye is secondary to tear film instability
and higher rate of evaporation. This is thought to be due to relative
androgen deficiency. Androgens play a role at various stages in lipid
metabolism. Meibomian glands are target organs for androgens.
Decreased levels of androgens therefore lead to altered lipid
component of meibomian secretions. This alters tear film composition
and leads to evaporative dry eye.
iv) Similarly, men on antiandrogen therapy(such as for prostate
cancer) are more commonly affected than others . Therefore, female
gender has been identified as a risk factor for the development of dry
eye .

19. • Symptoms and Signs:
i) The patients complain of a burning sensation of the eye, pain and
blurred vision.
ii) Foreign body sensation described as gritty feeling in eyes, and
there is also a hyperaemia of the conjunctiva (red eye).
iii) Mucus discharge and crusts are not uncommon.
iv) So the dominant findings of Keratoconjunctivitis sicca are two:
diminished corneal tear meniscus and abnormal Schirmer’s test.

20. • Treatment:
i) The primary goal in managing dry eye is to replenish or preserve
the tear film. The treatment is a combination of several actions.
ii) The patients should avoid dry environments and
overexposure to the sun.
iii) Natural tear substitutes are used
iv) In extreme cases occlusion of the lacrimal drainage, tarsorrhaphy
may be required in order to eliminate the problem.

21. Episcleritis
• Scleritis and episcleritis are the second most common ocular
manifestation of rheumatoid arthritis with RA being the most
common autoimmune etiology associated with scleritis.
• Occurs in 4% - 10% of RA patients.
• There are two forms of episcleritis: Simple episcleritis and the
Nodular episcleritis. The nodular is characterized by the presence of
subconjunctival nodules that are mobile over the sclera. The simple
(diffuse) episcleritis is more common.

23. • Symptoms and Signs:
I. The symptoms include sudden onset, with mild photophobia and
discomfort, no visual impairment.
II. Also mild pain may radiate into cheek,eye brows, temples.
III. The signs of episcleritis include bright red appearance of the eye
with engorged blood vessels.
IV. Also, there is no tenderness on palpation(Painless).
• Treatment:
I. Topical/oral steroids or NSAIDs.
II. Initial treatment of episcleritis should be focused on relieving
discomfort and stopping progression of the disease.

24. Scleritis
• Scleritis occurs with the same percentage as episcleritis does.
• In RA it is 4% - 10%. RA is a common cause of Scleritis.
• Scleritis may be diffuse, nodular, or necrotizing. Patients with non-
necrotizing scleritis usually have mild joint disease whereas
necrotizing disease tends to affect patients with severe long-standing
rheumatoid disease with extra-articular manifestations, most notably
rheumatoid nodules.
• Necrotizing scleritis without inflammation is a sign of long-standing
RA.

26. Symptoms and Signs
• Scleritis may have similar symptoms to episcleritis but Scleritis has a
gradual onset with a deep, boring pain which may radiate into cheek,
eyebrows and temples.
• Scleritis causes blurred vision and photophobia.
• Patients may have decreased visual acuity and tender nodules over
the sclera.
• There is more pain than in episcleritis and also there is tenderness on
palpation.
• The Scleritis patient will complain of pain while the Episcleritis-patient
will not.

27. Treatment:
• Initial treatment is by topical steroids.
• If there is non-necrotizing disease then treatment with topical and
oral NSAIDs.
• Also periocular steroid injections may be used in non-necrotizing and
necrotizing disease but their effects are usually transient.
• Corticosteroids by systemic route are used when NSAIDs are
contraindicated or ineffective. Cytotoxic/immunomodulatory agents
(such as cyclophosphamide, azathioprine, methotrexate,
mycophenolate mofetil) are usually necessary if the activity of the
disease is not fully controlled with steroids or they are used in order
to reduce the dose of corticosteroid in patients requiring long term
treatment.

28. • Immunosuppressive agents, including inhibitors of calcineurin:
cyclosporine and tacrolimus have been used as a long term
treatment.
• Monoclonal antibody/biological agents, such as infliximab and
rituximab are promising. Infliximab as an antagonist of TNF inhibits
the referred factor or serum or on the surface of target cells and
suppress the inflammatory process and rituximab as a monoclonal
anti-CD20 antibody for B lymphocytes eliminates the specific B
memory lymphocytes thereby inhibiting activation of antigen reactive
cells preventing their operation to create inflammation .
• Subconjunctival triamsinolone has also been used.

29. • The penetrating scleromalacia is a type of necrotizing scleritis without
inflammation, which typically may occur in older women with RA on
longer duration.
• The term penetrating is surprising since the penetration of the ball is
extremely unlikely and the integrity of the bulb remains thin but with
an intact layer of fibrous tissue.
• It forms necrosis of the sclera near the limbus without vascular
congestion. It has been very slow progress by scleral thinning and
uncovering the underlying choroid.
• The treatment may be effective in the initial stages, otherwise the
phthisis of the bulb follows.

30. Scleromalacia Perforans

31. Keratitis
• Keratitis is another very important aspect of the ocular
manifestations. Corneal disease in patients with RA can be an isolated
complication, but it is mostly associated with keratoconjunctivitis
sicca (a form of anterior scleritis).
Symptoms and Signs
• Keratitis is being characterized by pain with photophobia, foreign
body sensation, red eye, tearing and decreased vision.
• Keratitis is caused by infiltration by inflammatory cells and maybe
characterized by corneal opacification or by corneal vascularization,
which can lead to ulceration.

32. • Peripheral ulcerative keratitis (PUK) is also associated with RA, which
may lead to rapid corneal keratolysis, perforation of the globe and
visual failure and is associated with systemic vasculitis in more than
50% of cases , which carries a high mortality rate and needs early and
aggressive treatment.
• The clinical presentation of PUK is variable, it may present after
intraocular surgery or arise de novo, and typically patients describe a
non-specific foreign body sensation with pain, watering eye and
reduced visual acuity.
• The peripheral cornea has morphological and immunological
characteristics that predispose to autoimmune inflammation. Unlike
the central avascular cornea, the peripheral is provided with nutrients
from the capillary.

34. • The vascular architecture of limbus is suitable for IgM accumulation,
complement C1 and immunocomplexes. The deposition of immune
complexes triggers the classical complement pathway, which in turn
induces chemotaxis of inflammatory cells, particularly neutrophils and
macrophages. These cells can release collagenases and other proteases
that destroy the corneal stroma.*
• Moreover, the proinflammatory cytokines such as interleukin-1 ,stimulates
stromal keratocytes to produce metalloproteinases, which may accelerate
destructive procedure.
• PUK described local imbalance in the ratio of the levels of a particular
collagenase (MMP-1) and the inhibitor (TIMP-1) and it has been suggested
that this imbalance is responsible for the rapid keratolysis*
*Silva, B.L., Cardozo, J.B., Marback, P., Machado, F.C., Galvão, V. and Santiago, M.B. (2010) Peripheral Ulcerative Keratitis: A
Serious Complication of Rheumatoid Arthritis. Rheumatology International, 30, 1267-1268.

35. Treatment
• Without treatment, the disease maybe self-limited.
• Treatment includes NSAIDs, topical/oral/IV corticosteroids and
Cytotoxics .
• Systemic administration of corticosteroids are used to treat acute
phase and cytotoxic immunomodulators (cyclophosphamide,
methotrexate, azathioprine) for long-term treatment.
• In cases of perforation PUK application corneal tissue glue or amniotic
membrane patch or keratoplasty.
• Systemic administration of cyclosporin as an immunosuppressant,
when the RA is in advanced stages. The decision regarding the
duration of treatment depends on whether associated with
underlying systemic vasculitis, response to treatment. Particular
caution is required when prescribing topical steroids to prevent
further thinning of the cornea*.
*Patel, S.J. and Lundy, D.C. (2002) Ocular Manifestations of Autoimmune Disease. 66.

36. Uveitis
• Uveitis (anterior uveitis/iridocyclitis, intermediate uveitis, posterior
uveitis/chorioretinitis, panuveitis) are several forms of intraocular
inflammation that may occur in rheumatoid arthritis .
• The clinical signs are reduced visual acuity, inflammatory infiltration
of the anterior chamber, synechiae and miosis .
• Treatment includes cycloplegics, topical steroids and
immunosuppressants.

38. Systemic Lupus Erythematous
• Systemic lupus erythematous is an autoimmune disease in which the
organs and cells undergo damage initially mediated by tissue binding
autoantibodies and immune complexes.
• Ocular manifestations cause significant morbidity in their own right,
but can also be a useful indicator of underlying systemic disease
activity. Although early recognition and treatment have led to a
reduction in severe ocular complications. Ocular involvement in SLE is
still a potentially blinding condition.
• Gender plays a key role with women being nine times more
commonly affected than men*
*MariaM.Choudhary et al, Gender and Ocular Manifestations of Connective Tissue Diseases and Systemic
Vasculitides Journal of Ophthalmology Volume 2014, Article ID 403042, 8 pages

39. • Ocular manifestations in SLE are fairly common, potentially sight
threatening and may be the presenting feature of their disease .
• SLE may affect almost any part of the eye and visual pathway.
Additionally drugs used in the treatment of SLE may cause ocular
problems such as cataract or retinopathy.

40. Pathology
• SLE may cause ocular disease by a number of mechanisms including
immune complex deposition and other antibody related mechanisms,
vasculitis and thrombosis. Immune complex deposition has been
identified in blood vessels of the conjunctiva, retina, choroid, sclera,
ciliary body, in the basement membranes of the ciliary body and
cornea, in the peripheral nerves of the ciliary body and conjunctiva*.
• Antibody dependent cytotoxicity may cause retinal cell death and
demyelination of the optic nerve. Pathogenic circulating antibodies
include anti-phospholipid antibodies (APLA) and antineuronal
antibodies
* Karpik AG, Schwartz MM, Dickey LE, Streeten BW, Roberts JL. Ocular immune reactants in patients dying
with systemic lupus erythematosus. Clin Immunol Immunopathol 1985;35:295–312

41. Symptoms and signs
i. Pain (often accompanied by visible inflammation or redness)
usually indicates significant external/anterior segment disease.
ii. Problems with vision (blurring, distortion, double vision usually
indicates posterior segment/neuro-ophthalmic disease).
Causes of Red Eye in SLE
i. Common - Dry eye (kerato-conjunctivitis sicca)
ii. Less common – Episcleritis, Scleritis, Conjunctivitis (non-infective)
iii. Rare - Keratitis (other than kerato-conjunctivitis sicca)
Anterior uveitis

42. Causes of loss of vision in SLE
• Anterior segment - Severe kerato-conjunctivitis sicca
• Lens - Cataract (secondary to inflammation and/or
corticosteroids)
• Vitreous - Vitreous haemorrhage (secondary to proliferative
retinopathy)
• Retina - Severe vaso-occlusive retinopathy
Central retinal vein occlusion (CRVO)
Branch retinal vein occlusion (BRVO)
Central retinal arteriole occlusion (CRAO)
Branch retinal arteriole occlusion (BRAO)
Exudative retinal detachment
Toxic maculopathy (secondary to malarial
treatment)

43. • Choroid - Lupus choroidopathy
Choroidal effusion
Choroidal infarction
Choroidal neovascular membranes
Neuro-ophthalmic - Optic neuritis
Anterior ischaemic optic neuropathy
Posterior ischaemic optic neuropathy
Optic chiasmopathy
Cortical infarcts

44. • External eye disease
i) Eyelid disease - SLE (and discoid lupus erythematosus) can present
with a discoid lupus-type rash over the eyelids. These discrete raised
scaly lesions must be distinguished from the much more common
chronic blepharitis (inflammation of lid margins). These lesions usually
respond well to systemic but not topical antiinflammatory therapy.

45. ii) Lacrimal system disease - Dry eye syndrome (keratoconjunctivitis
sicca) is the most common ocular feature of SLE (around a third of
patients) and is often associated with secondary Sjogren’s syndrome .
Usually, symptoms are relatively mild (irritation, redness) but severe
pain and visual loss may occur. A reduced tear film and corneal changes
are evident on slit-lamp examination. Tear production can be assessed
by the Schirmer test. Milder forms of dry eye can be treated with
artificial tear drops.
iii) Orbital disease - Rare ocular presentations include orbital masses,
periorbital oedema, orbital myositis, acute orbital ischemia and
infarction are rare presentations of SLE. A biopsy is often necessary to
confirm the diagnosis. Treatment is with systemic immunosuppression

46. • Anterior segment disease
i) Corneal disease - Although the most common, the changes of dry
eye syndrome are not the only corneal manifestation of SLE.
Recurrent corneal erosions (large breaks in the corneal epithelium)
typically present as a painful watery eye that comes on at waking
and improves over the course of the day.
Another corneal presentation is punctate epithelial loss. This may
respond to systemic antimalarials suggesting that this may be an
autoimmune rather than a dry eye phenomenon*. Peripheral ulcerative
keratitis is rare and is an ominous marker of the presence of active
systemic vasculitis. Acute unilateral corneal stromal infiltration and
oedema has been reported and responds rapidly to topical
corticosteroid therapy.*
*Foster CS. Ocular surface manifestations of neurological and systemic disease. Int Ophthalmol Clin 1979;19:207–42.

47. ii) Episcleral and scleral disease - Episcleritis (superficial) and scleritis
(deeper inflammation of the sclera) are both seen in SLE, and may be
the presenting feature of the disease. Episcleritis usually presents with
mild, if any, irritation and redness due to injection of the superficial
blood vessels.
Scleritis is much more painful, may be sight threatening and requires
urgent assessment by an ophthalmologist. The pain is so severe that it
can wake the patient from sleep; it may be described as an ‘ache’ or
‘boring’ and may be generalized to the whole eye or the side of the
face..

48. • Anterior scleritis may be diffuse or nodular in distribution. Rarely it
may result in significant destruction (necrotizing scleritis) leaving an
area of scleral thinning.
• Posterior scleritis does not cause a red eye (unless it extends
anteriorly) but may cause visual problems, with blurring, change in
refraction and double vision. Although features may be present on
fundoscopy (oedema, choroidal detachments, exudative retinal
detachments), the diagnosis is most easily confirmed on B-scan
ultrasonography.

49. • Episcleritis does not usually require treatment, although artificial
tears may be soothing. The presence of scleritis may indicate activity
of the underlying disease and requires systemic therapy, ranging from
non steroidal anti-inflammatory drugs like flurbiprofen to
corticosteroids and other immunosuppressive agents (e.g.
cyclophosphamide, azathioprine, methotrexate, cyclosporin or
mycophenolate)
iii) Other anterior segment complications - Conjunctival inflammation
is uncommon. It presents with irritation, redness and may be
associated with lid follicles

50. • Posterior segment disease
i) Retinal disease - Retinal disease affects around 10% of SLE patients,
reflecting a reduction in frequency associated with improved control of
systemic disease. Mild retinopathy may be asymptomatic but more
severe disease may cause loss of vision, field defects, distortion or
floaters. Such visual symptoms are therefore an indication for urgent
ophthalmic review. The retinal signs often parallel the severity of
systemic inflammation, and may indicate inadequate control of the
systemic disease. The presence of APA is associated with more severe
retinopathy and vascular occlusions.*
*R. R. Sivaraj et al, Ocular manifestations of systemic lupus erythematosus, Rheumatology 2007;46:1757–
1762,Advance Access publication 5 August 2007

51. • Mild lupus retinopathy consists of cotton–wool spots, perivascular
hard exudates, retinal haemorrhages and vascular tortuosity.
• Other retinal presentations include large vessel occlusions (central
and branch retinal vein occlusions, central and branch retinal arteriole
occlusions) that are more common in the presence of APA,
pigmentary changes (pseudo-retinitis pigmentosa) and exudative
retinal detachments secondary to choroidal disease.

52. • The mainstay of treatment for significant retinal disease is systemic
immunosuppression. Initial treatment is usually with oral
corticosteroids (e.g. prednisolone 1mg/kg/day), but may be preceded
by intravenous methylprednisolone (e.g. 500mg–1g daily for 3 days).
• ii) Choroidal disease - Choroidal disease is less common than
retinopathy but is probably underdiagnosed as a cause of visual loss
in SLE.

53. Neuro-ophthalmic disease
Optic nerve disease - Optic nerve disease occurs in around 1% of
patients with SLE , and includes optic neuritis and ischemic optic
neuropathy.
Optic neuritis presents acutely with unilateral loss of vision associated
with pain that is worse with eye movements. The prognosis is worse in
SLE associated optic neuritis, with more than half having a persistent
central scotoma and progressing to optic atrophy. Pathological studies
demonstrate infarction of the optic nerve secondary to extensive
arteriolar fibrinoid necrosis . Acute optic neuritis may also be bilateral
and associated with transverse myelopathy
In contrast to optic neuritis, optic neuropathy in SLE typically presents
with bilateral, acute painless loss of vision associated with an altitudinal
or arcuate field defect, with or without optic disc swelling. This is due to
occlusion of the small vessels of the optic nerves, which leads to
demyelination in mild cases or axonal necrosis in more severe cases

54. • Bilateral optic neuropathy that improves with immunosuppressive
treatment is suggestive of a more generalised CNS vasculitic
pathology .
• Visual prognosis following optic neuropathy is generally poor,
although good outcomes have been reported. Recurrence usually
worsens the prognosis. Occasional improvement following early
treatment with corticosteroids or pulsed cyclophosphamide have
been reported, with some patients needing anticoagulation in
addition to immunosuppression.

55. Polymyositis and Dermatomyositis
• Polymyositis and Dermatomyositis are a group of autoimmune
diseases characterized by inflammation of the skeletal muscles ;
when there is dermatological involvement , the condition is referred
to as dermatomyositis.
• Genetic factors play an important role and a strong association has
been identified with human leukocyte antigens HLA-B8 and DR3 and
DR52.

56. • Inflammatory myositis is relatively rare compared to other
rheumatologic diseases with around 5 new cases per million being
reported annually.
• Women are more commonly affected than men.
• Around 15% of the cases are associated with an underlying
malignancy.

57. • Ocular manifestations are as follows;
i. Heliotrope rash or purplish discoloration of the eyelids is the most
common ocular manifestation.
ii. Pediatric case reports exist about retinal vasculitis.
iii. Occasional cases of internuclear ophthalmoplegia have also been
reported.
iv. Involvement of the extraocular muscles is extremely rare and can
cause pain and ophthalmoplegia.

58. iv. The associated peri-orbital redness and oedema producing ptosis,
chemosis, and exophthalmos may initially be mistaken for infective
orbital cellulitis.
v. Additional features seen are conjunctivitis and iritis ,
episcleritis and uveitis with glaucoma.
• No gender differences have been observed in the incidence or
severity of ocular problems in the patient population.

59. Visual loss from optic neuropathy
• Optic neuropathy has been described in patients with dermatomyositis,
but only in association with retinopathy usually producing multiple
cotton wool spots is the most common finding and may be
asymptomatic.
• Pathology:
i) Retinal involvement is believed to be due to vasculitis with
endothelial disruption and platelet thrombi.

60. • Retinopathy is believed to be more common in children with
dermatomyositis because accompanying vasculitis is more common at
a younger age.
ii) Decreased vision has been attributed to retinopathy and infarction
within the retinal nerve fibre layer.
iii) Intraretinal haemorrhages and macular exudates have also been
described as causing decreased vision in patients with
dermatomyositis.

61. • Signs and symptoms
I. Blurred vision in both eyes that is gradually progressing.
II. The relative afferent pupillary defect, dyschromatopsia, visual field
defects and optic disc oedema in the absence of retinopathy give
evidence that the visual loss is from an optic neuropathy and not a
retinopathy.
• Treatment
I. Corticosteroid therapy (oral/iv)
II. Immunosupressants (high dose)

62. Marfan’s syndrome
• Marfan's syndrome (MFS) is an autosomal dominant connective
tissue disorder, caused by mutations in FBN1 gene on chromosome
15, which codes for the connective tissue protein fibrillin.
• Abnormalities in this protein often lead to a myriad of skeletal,
cardiovascular, and ocular abnormalities.

63. • Around 41% of the patients with MFS are initially seen for an ocular
pathology and diagnosed by an ophthalmologist.

64. • Ocular manifestations include;
i. Ectopia lentis
ii. Cataracts
iii. Myopia
iv. Astigmatism
v. Strabismus
vi. Retinal detachment
vii. Glaucoma

65. Ectopia lentis
Found in 50–80% of the eyes.
• Signs and symptoms
I. Fluctuating blurred vision.
II. Monocular diplopia
III. Pain
IV. Characteristically, lens tend to be displaced in superior-temporal
direction and often bilateral.

67. V. Phacodonesis and/or iridodonesis may commonly present even in
the absence of evident lens dislocation.
VI. Develop cataracts several decades earlier compared to unaffected
individuals.
• Treatment
I. Surgical management of these cases with anterior lensectomy,
limited vitrectomy, and iris/scleral-fixated intraocular lenses or
aphakic correction are indicated where ametropia cannot be
achieved by optical refraction or when the refractive status becomes
unstable, in the presence of significant anisometropia, complete
dislocation of the lens and lens-induced glaucoma or uveitis.

68. Myopia
Present in around 40% of the cases.
• Pathology
i. These patients develop lenticular myopia resulting from
spherophakia and axial myopia resulting from globe elongation.

69. Astigmatism
• Pathology
i. Combined effect of corneal toxicity and lens subluxation. The cornea
is typically flat in these patients.
ii. Anterior chamber angle in these patients is usually wide with
immature trabecular meshwork and displacement of schlemm's
canal.
iii. Sphincter and dilator muscle of the iris are usually underdeveloped
causing eccentric pupil or mydriasis. Iris transillumination defects
may present in some cases.

70. Strabismus
• Incidence in strabismus in patients with MFS is increased compared to
general population.
• Specifically, exotropia has been reported in up to 11.7% of patients with
MFS, whereas esotropia has been found in 2.1% of patients.
• Pathology
i. Abnormal afferent visual inputs to cortical centers caused by ectopia
lentis and craniofacial abnormalities may contribute to the higher
prevalence of strabismus in MFS.

71. Retinal detachment
• Common ocular complication.
• The incidence of retinal detachment in MFS ranges from 5% to 11%
and more commonly seen in younger adults.
• This risk further increases (38%) with the presence of ectopia lentis or
following surgical extraction of the lens.

72. Glaucoma
• Around 35% of the patients develop glaucoma during their lifetime
and primary open-angle glaucoma is the most common.
• Other causes of glaucoma in these patients are lens dislocation and
surgery.

73. • Overall treatment
i. Patients must be closely followed up for complications such as
glaucoma, retinal detachment, cataract, and amblyopia.
ii. Awareness and prompt recognition of the ocular manifestations of
MFS by the general ophthalmologist, especially in the absence of
family history and distinct musculoskeletal features, may not only
enable the improvement and preservation of sight, but by relevant
referrals to the internists and comprehensive management by a
multidisciplinary team including a geneticist, orthopedics, and
cardiologist, may also improve the morbidity and mortality of these
patients.

74. Osteogenesis imperfecta
• Osteogenesis imperfecta is a genetic disorder of connective tissue
characterized by increased bone fragility and usually associated with
hearing loss , abnormalities of dentition and blue sclera.
• Ocular manifestations include;
i. Blue sclera
ii. Blindness
iii. Retinal detachment

75. • Most affected individuals have mutation in either the COL1A1 or
COL1A2 genes that encode the chains of type I procollagen.

76. Blue sclera
• The sclera can vary in color from normal to a slightly bluish to a bright
blue.
• Pathology
i. The blue sclera result from thinning of abnormal sclera , leading to
the transmission of the uveal tissue to the observer.
• Treatment
I. Vitrectomy

77. Blindness
• Blindness usually results from corneal opacity , secondary glaucoma
and hyperplasia of the vitreous.

78. Retinal detachment
• Pathology
i. Patients with osteogenesis imperfecta are more prone to retinal
detachment because decreased scleral rigidity leads to increases
tractional forces on the peripheral retina.

79. • Treatment
For uncomplicated cases the standard for repair is ;
I. Scleral buckling surgery
II. Pneumatic retinopexy
III. Primary vitrectomy
For acute or chronic macular-sparing shallow retinal
detachments without proliferating vitreoretinopathy;
I. Laser photocoagulation

80. Scleroderma
• Scleroderma is a generalized connective tissue disease of unknown
origin with heterogeneous manifestations
• It is characterized by abnormal fibroblast proliferation leading to
deposition of extracellular matrix in the skin, blood vessels, and
viscera.
• This results in stiffening of the connective tissue structures in the skin
and body organs.

81. • Symtoms and signs
i. Telangiectasia
ii. Eyelid changes : dermal sclerosis of the eyelids and Lid stiffness is
associated with woody texture on palpation and difficulty with lid
eversion.
iii. Conjunctival changes: This comprises of vascular congestion,
telangiectasia and varicosities of conjunctival vessels, intravascular
sludging, and loss of fine vessels.

83. iv. Lacrimal function changes :A tear defect of varying severity.
V. Iris changes :punctate defects of the iris pigment epithelium
appearing as Spotty areas of transillumination in all zones of the iris
Vi. Fundus changes : There will be retinal arterial sclerosis with
constriction of the affected venous branch due to sclerosis of the
adjacent arterial adventitial sheath.

84. • Treament
• Telangiectasia such as those on the face, can be treated with local
laser therapy. Sun exposure should be minimized as it can worsen
telangiectasias.
• Lacrimal function changes :Topical lubricants

85. Stills Disease
• It is a rare systemic autoinflammatory disease characterized by the
classic triad of persistent high spiking fevers, joint pain , and a
distinctive salmon-colored rash.

86. • Symptoms and signs
i. Iridocyclitis :This iridocyclitis is commonly of a quiet sero-fibrinous
non-granulomatous type.
Fine posterior synechiae commonly develop
and may be seen extending as filmy grey bands
from the anterior surface of the iris near
the pupil margin to the anterior lens capsule.

87. • The quiet insidious nature of the iridocyclitis is characteristic.
• There is no pain . The inflammation may subside for long periods-
months or years and then recur.
• Iridocyclitis is sub-acute in nature with definite redness of the eye,
photophobia and some discomfort.

88. Treatment
• It is mainly by mydriatics and cortisone. Suppressing inflammation
and preventing adhesions is the main stay of the treatment.
• Cortisone and hydrocortisone 1 percent drops and ointment is used.
Drops should be instilled 2- or 4-hrly during the day and the ointment
before going to sleep at night.

89. ii. Band Keratopathy (Corneal Band Opacity).-This is a striking feature
and common complication of the ocular inflammation occurs in still's
disease only in association with iridocyclitis.
• The opacity usually extends across the cornea in the inter-palpebral
area, more below than above the centre of the
pupil and is subepithelial at the
level of bowman's membrane.

90. • It consists of closely-grouped grey dots interspersed with clear round
lacunae of varying sizes. These clear fenestrations are said to be caused
by the corneal nerve filaments which perforate bowman's membrane to
form the subepithelial plexus.
Treatment
• Subconjunctival injections of cortisone.
• Chelation : EDTA(Edetate Disodium)
• If there is sufficiently gross opacity, lamellar keratoplasty might seem to
be indicated.

91. iii. Cataract :This forms the third feature of what might be called the
"ocular triad" of Still's disease.
• It is seen typically as a complicated cataract, usually first in the
posterior lens cortex and then in the anterior cortex, and it matures
rapidly, causing profound interference with vision.
• Treatment : Repeated needling operations ,but only when the
iridocyclitis has been fully controlled and the eye has been free from
inflammation for some months.

92. iv. Fibrinous exudate : inflammatory deposits on the lens capsule in
the pupillary area can also cause considerable interference with
vision and may be followed by localized subcapsular opacities.
V. Secondary glaucoma: It is another possible complication. Extensive
adhesions between iris and lens result in seclusio pupilli and iris
bombe which must be promptly relieved by iridectomy.

93. vi. Hypotony can also occur as a terminal event when the ciliary body
is so disrupted by prolonged inflammation that the ciliary processes
can no longer produce aqueous humour, phthisis bulbi then gradually
develops.

94. Behcet’s Disease
• Behçet’s disease (BD) is a chronic, relapsing inflammatory disorder of
unknown etiology and characterized by obstructive vasculitis. It can
involve both the arteries and veins of almost any organ and
characterized by recurrent oral and genital aphthous ulcers, ocular
inflammation, and skin lesions.
• The frequency of ocular involvement in patients with BD is
approximately 70%-90% . The ocular disease manifests approximately
in 2-3 years after the initial symptoms noted.
• Males are more frequently involved, has an earlier disease onset, and
has a more severe disease.

95. Occular Manifestations – Symptoms and Signs
• The characteristic ocular involvement is a relapsing remitting
panuveitis.
• The ocular inflammatory episodes in BD are characteristically
associated with a sudden severe onset of visual loss. Severity and
number of repeated inflammatory attacks involving the posterior
segment determine the extent of permanent structural changes and
the resultant rate of irreversible visual loss. Because of that, Behçet
panuveitis is a medical emergency, which must be treated
immediately.

96. ANTERİOR SEGMENT:
• Iridocyclitis ± hypopyon, Secondary glaucoma ,Secondary cataract
• Less frequent findings:
Episcleritis,Scleritis,Conjunctivitis, Subconjunctival haemorrhage,-
Conjunctival ulcers, Filamentary keratitis,Corneal immune ring opacity.

97. POSTERİOR SEGMENT:
• Vitritis, Retinal perivasculitis, Retinal hemorrhage and infarction due
to occlusive vasculitic attacks, Retinitis, Diffuse retinal or optic disc
edema, Optic disc hyperemia, Venous engorgement, Cystoid macular
edema, Macular ischemia, Macular scarring, Pigment epithelial
changes,Epiretinal membrane formation.
End stage ocular disease:
• Optic atrophy, Vascular attenuation and sheathing, Diffuse retinal
atrophy.

98. Treatment
• The primary goals of management are symptom control, early
suppression of inflammation and prevention of end-organ damage.
Even though therapy of acute disease is essential, to prevent or at
least to decrease the number of repetitive ocular and systemic
inflammatory episodes is important.
• Many treatment modalities have been tried in ocular BD with varying
claims of success. For the time being, the most commonly used
agents are corticosteroids, cytotoxic drugs, colchicine, and tacrolimus.

99. Ehler‘s Danlos Syndrome
• It’s a heterogenous group of inherited connective tissue disorders
Characterized by hyperextensible skin, hypermobile joints and
connective tissue/ cutaneous fragility.
• These symptoms are result of gene mutations affecting the structure of
various collagen types.
• Mainly affecting the eye , as 80% of eye is made up of collagen.
• The frequency of Ehler's Danlos syndrome has been estimated at 1
case in 50,000 to 1 case in 200,000 and prevalence is reported to be 1
case in approximately 400,000.
• Type 6, the ocular form, affects 2%of patients and is inherited in an
autosomal recessive pattern.

100. Signs and symptoms
• Keratoconus-Abnormal corneal curvature occurs when it becomes
cone shaped, usually occurs in 2nd & 3rd decade of life.

101. • Angioid streaks - These are cracks in the Bruch's membrane or
anchoring membrane of retina. The streaks usually radiate from optic
disc .

102. • High myopia- characterizd by shortsightedness. Results because cornea
is to steep to focus point of light rays entering the pupil in front of the
retina.
• Blue sclera-bluish appearance attributed to a thinning of sclera,
noticeable at the limbus..

103. • Posterior staphyloma- is a streching or distortion in the posterior aspect
of eye. Scleral tissue bubbles which results in a significant myopic shift
i.e, increased shortsightedness

104. • Retinal detachments-preceded by a shower of sparks & floaters are
trapped debris in vitreous of the eye. Blue sclera-bluish appearance
attributed to a thinning of sclera, noticeable at the limbus.

105. • Macular degeneration-contains the highest concentration of vision
receptors, when the macula atrophies causing pigment changes and
decrease in keen vision to occur.

106. • Glaucoma- increase in intraocular pressure which leads to vision
impairment till blindness, as well as a progressive loss of peripheral
vision.
• Cataracts - the lens tissue discolours naturally resulting in cloudy lens.
• Dry eye - results in when normal coating of tears on the eye is
diminished.

107. Treatment
i) Medical care
• Eye drops are used for dry eye.
ii) Surgical care
• Corneal transplant is required for keratoconus.
• Corrective lenses are an effective treatment for high myopia

108. Systemic Vasculitidies
• The vasculitic syndromes have been classified by the predominant
sizes of the blood vessels most commonly involved.
• Ophthalmic manifestations are protean and nonspecific and are
secondary to vasculitis of the ophthalmic circulation.
• Conjunctivitis, episcleritis, and scleritis are the most common
presentations. The patients typically present with painful red eye
except in episcleritis where the condition might be painless and
usually self-limiting

109. • Cicatrizing conjunctivitis resulting in symblepharon more commonly
of the upper eyelid can be seen in uncontrolled disease .
• Scleritis associated with systemic vasculitis requires more aggressive
treatment than idiopathic scleritis or from other etiologies.
• Retinal arterial involvement can be in the form of central retinal
artery occlusion or a branch of it. Involvement of posterior ciliary
circulation can cause ischemic optic neuritis.

110. Sjogren’s Syndrome
• It is a chronic ,slowly progressive autoimmune disease characterized
by lymphocytic infiltration of the exocrine glands resulting in
xerostomia and dry eyes.
• Occular Manifestations: Keratoconjunctivitis sicca
• Signs and Symptoms
i. Sandy gritty feeling under eyelids
ii. Accumulation of secretions in thick strands at the inner canthi
iii. Decreased tearing

111. iv. Redness ,Itching and increased photosensitivity.
v. Slit lamp examination shows punctate corneal ulcerations .
Treatment
i. Tear drops – Hydroxypropyl methylcellulose
ii. Corneal ulcerations – Eye patching and boric acid ointment.

112. Scleritis Anterior Uveitis Posterior Uveitis
Rheumatoid arthritis Rheumatoid arthritis Idioapthic
SLE SLE Sarcoidosis
Behcet’s disease Ankylosing spondylosis Behcet’s disease
Sarcoidosis Sarcoidosis
Dermatomyositis Reiters syndrome
Wegner,s granulomatosis Spondyloarthritis
Spondyloarthritis
Panuveitis
Idiopathic
Behcet’s disease
Sarcoidosis
Ankylosing spondylosis
Rheumatological Emergency :
i) Scleromalacia Perforans(RA)
ii) Acute iridocyclitis ( seronegative
spondyloarthritis)
iii) Retinal vein thrombosis(Antiphospholipid
syndrome)

113. References
• MariaM.Choudhary et al, Gender and Ocular Manifestations of Connective Tissue Diseases and Systemic
Vasculitides Journal of Ophthalmology Volume 2014, Article ID 403042.
• Foster CS. Ocular surface manifestations of neurological and systemic disease. Int Ophthalmol Clin
1979;19:207–42
• Karpik AG, Schwartz MM, Dickey LE, Streeten BW, Roberts JL. Ocular immune reactants in patients dying
with systemic lupus erythematosus. Clin Immunol Immunopathol 1985;35:295–312
• R. R. Sivaraj et al, Ocular manifestations of systemic lupus erythematosus, Rheumatology 2007;46:1757–
1762,Advance Access publication 5 August 2007
• Silva, B.L., Cardozo, J.B., Marback, P., Machado, F.C., Galvão, V. and Santiago, M.B. (2010) Peripheral
Ulcerative Keratitis: A Serious Complication of Rheumatoid Arthritis. Rheumatology International, 30, 1267-
1268.
• Waduthantri S. Ocular manifestations of Marfan's syndrome. Med J DY Patil Univ [serial online] 2017
[cited 2017 Jul 21];10:118-9.
• Diamantis Almaliotis et al, Ocular Manifestations in Rheumatoid Arthritis Open Journal of Ophthalmology,
2016, 6, 170-175 .

114. • R.H.West et al, Ocular involvement in scleroderma British Journal of Ophthalmology, 1979, 63, 845-847.
• Yonca Aydın Akova and Sirel Gür Güngör et al, Ocular Involvement in Behçet’s Disease ,review article.
• Kasper et al,Harrisons’s Principles of internal medicine 19th edition.

115. Thank you

118. Seronegative Spondyloarthropathies
• Ankylosing spondylitis:
Occular features occur in 25% of the patients
i. Uveitis
• Occular pain,redness and blurred vision.
• It classically alternates between the two eyes.
ii. Scleritis and conjunctivitis may rarely occur.

119. Reiters Syndrome:
i. Bilateral mucopurulrnt conjunctivitis(58%)
ii. Non granulomatous anterior uveitis
iii. Keratitis
iv. Anterior scleritis and episcleritis

120. Psoriatic arthritis:
• Anterior uveitis(7 – 20%) – Non granulomatous.
• Scleritis is srare.