This document discusses a case of a 58-year-old woman presenting with recurrent eye pain and redness in both eyes. On examination, she was found to have diffuse anterior scleritis in the right eye and posterior scleritis, with a history of rheumatoid arthritis. The document then provides an overview of scleritis, including classification, pathogenesis, diagnostic approach, and treatment strategies depending on the type of scleritis and any underlying conditions. Treatment may involve NSAIDs, corticosteroids, immunosuppressants like methotrexate, or biologics, sometimes with surgical intervention for necrotizing scleritis. Non-infectious scleritis can indicate serious systemic diseases.

1. Dr Pramod K Sharma
Retina , Uvea & ocular immunology service
VSS Medical College, Burla

2. Example
A 58 years lady preseneted with recurrent severe pain & redness which is
alternating to both eyes since last year. Her VA in right eye is reduced this time.
She is having joint pain for which she is on Aceclofenac 100mg SR OD,
Salazopyrin 1g BID since 2 years by her rheumatologist.
Her hands showed typical z deformity with subcutaneous nodule on fingers. She
is dyspneic at little work.
Her ocular exam shows fiery red superior bulbar congestion, tender to touch as
well as to ocular movement. VA – OD -6/12, OS- 6/6. OD Fundus shows choroidal
fold
Investigation – Microcytic hypochromic anemia, Leukocytosis with raised
neutrophil count, ESR raised, High +ve titre Rh factor,
B Scan showed thickened RCS complex OD
Her old radiograph of hand suggestive of RA
What is the Diagnosis and how we will approach ?

3. Scleritis
 Eighty % of exterior of eye ball is sclera
 Most of the ophthalmologist give less importance as it
takes no active part in visual function like cornea,
lens, retina, uvea and optic nerve but carries infinite
visual significance as it encompasses these visual vital
structures.

4.  But this rarity significant scleral issues at times coupled
with profound systemic life threatening diseases.
 Watson & Hazleman pointed out in their text book “The
Sclera & Systemic Disorders “ that 27% of patients with
Necrotizing Scleritis are dead with in 5 years from systemic
vasculitic lesion.
 Similarly Maza & Foster in their text “ The Sclera “ found
scleritis may be a harbinger of severe immune mediated
vasculitidis.

5. Special anatomic consideration
 Divided into 3 layers- episclera, scleral stroma, lamina
fusca.
 Has profuse sensory innervation through ophthalmic
division of trigeminal ( long anterior & short posterior
ciliary nerve). That is Why scleral inflammation is very
painful.
 Episcleral vessels has no muscular layer but has
endothelium with its basement membrane and
discontinuous layer of pericytes. Here artery to artery
anastomosis exists where blood oscillates and sites for
immune complex deposit. That is why microangiopathy
disorders ( e.g. RA, SLE, PAN etc. ) affects sclera.

6. Etiology
 Exogenous agents-
 Viruses- HSV, VZV, EBV etc have direct cytopathic effect and they or
their components induce antigens that invoke an immune response*
 Bacteria & mycobacteria
 Fungi
 Protozoa- acanthemoeba
*Lider M et al. The infectious etiology of Vasculitis. Autoimmunity
.2009;42(5):432-8.

7.  Endogenous Substances-
Immunological cross reactivity of
glycosaminoglycan,collagen between sclera and other
organ suggest auto immunity*.
*Coster L et al. The Dermatan sulfate proteoglycans of bovine sclera and their
relationship to those of articular cartilage. J biol chem.1987:262:3809

8. Pathogenesis
 Interaction of genetically controlled mechanisms with
environmental factors such as viruses or trauma gives rise
to an autoimmune process that damages the vessels
through immune complex mediated type III
hypersensitivity.
 Persistent immunological injury leads to granulomatous
response via type IV hypersensitivity

9. Classification*
 Episcleritis-
- Simple
- Nodular
 Scleritis
- Anterior
- Diffuse
- Nodular
- Necrotizing
-with inflammation
- without inflammation ( scleromalacia perforancs)
-Posterior Scleritis
*Watson PG, Hayreh SS. Scleritis and episcleritis. Br J
Ophthalmol. 1976;60(3):163–91

10. Diagnostic Approach
 5 phases of approach
 1. Investigation 0f the illness
 Interview
 Major complaints- pain, redness ,photophobia, tenderness, decreased VA
 History of present illness-
 Past history-any systemic illness that can cause scleritis, any illness that might
eventually modify future therapy
 Family history- Genetic relation frequently seen in RA,SLE, AS, ReA, Behcet’s
disease,atopy etc
 Past & present therapy history- type, route,dosage, response, side effects,
related complication , concomitant Rx for other condition and reason for
discontinuation of therapy
 Review of the system-

11.  Physical Examination
systemic exam- head & Extremities
Ocular Exam- 1. Day light exam, SL exam-diffuse,
Slit, red free light exam
2. General eye exam- VA, pupil &
EOM, Cornea, Ant Uvea, Lens, fundus, IOP

12.  2. Diagnostic tests
Blood & Urine tests
Unless the cause is infectious blood, urine lab test rarely establish a diagnosis of systemic disorder. So blanket testing is expensive & wasteful.
a. Rh factor- though 80% of RA patient is +ve for Rh factor but it is not specific test for RA. It’s high titre signifies severity of disease with extra articular manifestation.
b.Anti-CCP test – a better specificity test for RA than Rh factor.
c.ANA test – Ab to ds-DNA, ss-DNA, nRNP,sm RNP etc are indicative of autoimmune disease. Pattern of IF positivity has diagnostic significance.
d. ANCA test- PR-3 ( c-ANCA) specific for GPA, MPO( p-ANCA) specific for Microscopic polyangitis.
e. CICs- it’s detection is not essential of diagnosis but helps to support specific disorder. Also it’s level interpreted as response to therapy
f. Complement- Level of complement components decreased during complement activation. Ag-Ab reaction activates this pathway and consume complements as in auto-
immune disorder. Quantification of C3, C4 and CH50
g. HLA typing- Presence of certain HLA type increases the probability of presumptive diagnosis when clinical & radiological findings are equivocal. B27 for AS,ReA, B5 for
Behcet’s, DR4 for RA
h .Ab against infectious agents- FTA-ABS for syphilis, Lyme’s titre for Borreliosis, Ab for HSV,VZV etc
i. IGRAs- QuantiFERON-TB gold test, T-SPOT TB test
PCR
Smears & Cultures
Skin Testing
Radiologic Studies-
Chest x-ray, Sinus film, Sacro-illiac joint, limb joints
Other Imaging studies
A Scan, B-Scan, CT scan, MRI
 3.Biopsy
-detection of inflammatory microangiopathy in scleral or conjunctiva supports diagnosis of systemic vasculitis
- detection of infectious agents

13. 4. Data integration

14. Example
A 58 years lady preseneted with recurrent severe pain & redness which is alternating to both
eyes since last year. Her VA in right eye is reduced this time.
She is having joint pain for which she is on Aceclofenac 100mg SR OD, Salazopyrin 1g BID
since 2 years by her rheumatologist.
Her hands showed typical z deformity with subcutaneous nodule on fingers. She is dyspneic
at little work.
Her ocular exam shows fiery red superior bulbar congestion, tender to touch as well as to
ocular movement. VA – OD -6/12, OS- 6/6. OD Fundus shows choroidal fold
Investigation – Microcytic hypochromic anemia, Leukocytosis with raised neutrophil
count, ESR raised, High +ve titre Rh factor,
B Scan showed thickened RCS complex OD
Her old radiograph of hand suggestive of RA
What is the Diagnosis and how we will approach ?
 Diffuse Anterior Scleritis & posterior Scleritis with
Rheumatoid arthritis

15. Therapeutic Plan
 Episcleritis does not require any treament. Regrettably
many physician prescribe steroid preparations which has not
only have rebound effect but also side effects.
 If patient demand Rx or if his occupation demands as in actors ,
systemic NSAID may be instituted like scleritis for 6months with
taper.
 Episcleritis with systemic disorders requires specific therapy e.g.
SLE– HCQ, Gout-allopurinol, Rosacea- Tetracycline etc.
 Otherwise we recommend refrigerated tear substitute for
idiopathic episcleritis.

16. Infectious Scleritis
 With anti-microbial therapy ancillary anti-
inflammatory agents may be required e.g. Scleritis
associated with syphilis.
 Any patient with fungal etiology must not be under
corticosteroid.

17. Rx for Scleritis
 Systemic NSAID almost invariable effective. Sequential trials of
several NSAIDs may be required before one that is completely
effective found.
 We treat scleritis who responded NSAIDs, at least for 1 year
before attempting to taper and discontinue.
 Patients with associated disease require specific treatment e.g.
Rosacea, gout, atopy
 Patients with connective tissue or collagen vascular diseases
requires special consideration. Scleritis with GPA, PAN, RP
require aggressive therapy with cytotoxic agents like
cyclophosphamide.

18. Scleritis with RA
Diffuse scleritis
 Our first choice is NSAIDs. Before concluding for additional
systemic medications we go through 3 different NSAIDs .
 Our next step is additional short course of systemic
prednisolone typically 1mg/kg, taper when scleritis has resolved
totally and then switch to alternate day therapy once dose down
to 20mg/day.
 If no recurrence with topical steroid discontinuation and
20mg/day prednisone, next approach is 40mg on every other day
for 2 weeks, then 30mg, 20mg,15mg,10mg,7.5mg,5mg and finally
discontinued.
 Those who do not respond require low dose MTX weekly.

19. Nodular scleritis
Majority respond to systemic steroid program but some
require once a week MTX 15mg/week ( < 50kg, start
10mg ) as starting dose, which can be increased upto
35mg/week depending upon response.

20. Necrotizing scleritis
 It must be treated with systemic immunosuppressant. Systemic
prednisone with immunosuppressant works well.
 If unilateral and not severe, systemic prednisone and weekly MTX is
of choice.
 In bilateral and severe, not responding to MTX , Azathioprine 2mg/kg
is prefered. Other options available are Mycophenolate, Cyclosporine-A
& Biologic agents ( Infliximab, Adalimumab, Rituximab etc.).
 Cyclophosphamide is considered in severe or rapidly progressive cases.

22. Surgical treatment
 Virtually necessary for scleral reinforcement in necrotizing scleritis
where globe is threaten to perforate.
 Donor Sclera, periosteum, fascia lata are the graft material.
 However graft can not solve the problem. Essential ingredient is to
control or cure the underlying immunoregulatory dysfunction.

23. Take home message
 Non infectious Scleritis may be an ocular
manifestation of severe life threatening systemic
disease.
 Timely and judicious use of IMT can save visual
morbidity and life of the patient.