OCULAR INFLAMMATION
From the 28th Annual Scientific Meeting, presented by the Utah Ophthalmology Society, Eye MDs of Utah, Salt Lake
City, UT
Paul L. Zimmerman, MD, Associate Professor of Ophthalmology, Sanford School of Medicine, University of South
Dakota, Sioux Falls; Private Practice, Black Hills Regional Eye Center, Rapid City, SD
| Etiology: autoimmune response in sclera, possibly due to trauma, viral illness; inflammatory cascade causes vasculitis,
tissue edema, sometimes destruction, and necrosis
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| Classifications: episcleritis differs from scleritis; anterior scleritis—diffuse, nodular, necrotizing with or without inflammation;
posterior scleritis; episcleritis—benign, self-limiting; mild-to-moderate focal discomfort; not always
treated; patients self-medicate with naproxen; speaker does not use topical steroids for self-limiting disease (prevents patient
from using steroid for mild recurrent problems); scleritis—potentially severe, sight-threatening disease; significant
tissue destruction; complications (eg, uveitis, glaucoma, cataracts, macular edema, phthisis bulbi in severe cases); long-
term, persistent, or recurrent; occasionally isolated
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| Episcleritis symptoms and signs: mild-to-moderate pain, irritation, and lacrimation; sectorial areas of redness, rarely
diffuse; tender and nodular; consider scleritis when presented with occasional mild anterior chamber reaction; “roadmap
appearance” with chemosis and engorged superficial and deep episcleral vascular plexus; no scleral substance involvement;
technique for differentiating nodular episcleritis from nodular scleritis—shine very thin and bright slit-beam
from side; episcleritis produces 2 light reflexes from conjunctiva and chemosis off scleral surface; nodular scleritis produces
single reflex, with little tissue edema
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| Scleritis symptoms and signs: pain usually severe; one class of patients with little or no pain; erythema; photophobia;
blurred vision; malaise (due to rheumatologic disease or eye pain); global or sectorial erythema; brick red or violaceous
sclera; apparent in sunlight; uveal presentation with necrotizing scleritis; mild anterior chamber reaction; nodules; surrounding
episcleral inflammation with chemosis; most patients with scleritis have episcleritis with involvement of deep
episcleral plexus; presence of scleral edema; uveitis corollary
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| Presentation: boring (ie, intruding) pain radiating to jaw and temple; unilateral or bilateral facial pain (roadmap); deep
episcleral plexus with overriding episcleritis and scleral edema; new vascular channels within sclera; not seen in episcleritis
or elsewhere; treat systemically
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 | Diffuse anterior scleritis: most common form; seen with rheumatoid arthritis (RA); sectorial; widespread inflammation;
vascular pattern distortion; engorged conjunctival vessels; when global chemosis present, referred to as “brawny”
scleritis (tissue fluid in episcleral spaces and scleral edema)
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| Nodular anterior scleritis: second most common type; 16% to 44% incidence; localized nodules, usually single nodule;
usually unilateral; nodules intrinsic to sclera; no conjunctival movement when gently pushed with cotton applicator (in
nodular episcleritis, conjunctiva and fluid move); point tenderness
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| Necrotizing anterior scleritis: less common than diffuse or nodular types; disease more significant; inflammation; vascular
congestion, distortion and occlusion; bluish discoloration; uveal ciliary body or choroid noted through absent sclera; associated
anterior or posterior uveitis; conjunctival necrosis indicates systemic disease (ie, Wegener’s granulomatosis,
polyarteritis nodosa, RA); requires aggressive work-up; necrotizing scleritis without inflammation (sclero- malacia perforans)
occurs in elderly women with long-standing RA; conjunctiva with no Tenon’s; bare choroid present
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| Posterior scleritis: low incidence; frequently underdiagnosed; may represent 10% to 20% of scleritis; presentation—
symptoms of orbital disease; full-appearing orbit; proptosis; decreased vision; Marcus Gunn pupil; pain on extraocular
muscle movement; diplopia; lid edema; must differentiate between posterior scleritis and other orbital processes; some
anterior scleritis possible; inflammatory progression behind equator; subretinal masses; exudative retinal detachments;
severe visual changes; signs of proptosis; chorioretinal folds; subretinal edema; serous retinal detachment; subretinal
mass
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| Peripheral ulcerative keratitis (PUK): seen in patients with scleritis; indicative of serious systemic disease; requires diligent
work-up, review of systems; true scleritis in 25% to 33% of patients; isolated idiopathic disease diagnosis of
exclusion
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| Associated collagen vascular diseases: RA most common; occasionally systemic lupus erythematosis; relapsing
polychondritis rare condition, but common in patients with anterior scleritis; ankylosing spondylitis, Reiter syndrome
(rare; patients with “hot” unilateral iritis); dermatomytosis; scleroderma; Still’s disease; patients with polyarteritis nodosa
or Wegener’s granulomatosis die if untreated
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| Other associated disorders: IgA nephropathy (patients have diffuse generalized anterior scleritis [“red eye”]); occasional
episcleral edema (keep comfortable); gout (rare); do not overlook erythema nodosum and lethal midline granuloma;
anterior scleritis, inflammatory bowel disease (PUK common); infectious diseases causing scleritis—syphilis;
herpes (simplex and zoster); acanthamebiasis; mucomycosis; diabetics with severely compromised immune systems usually
have orbital process; Lyme disease; postoperative pterygium with conjunctival graft; use of mytomycin C and fluorouracil
(5-FU) in glaucoma filtering surgery; bacteria (especially Pseudomonas species, and other gram negative types)
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| Work-up: include patients with recurrent episcleritis (except those with blepharitis or negative review of systems)
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| Tests and screening: complete blood cell count (CBC) with differential; syphilis serology; fluorescent treponemal antibody-
absorption (FTA-ABS) test (speaker prefers to Venereal Disease Research Laboratory [VDRL] test and rapid plasma reagin
[RPR] screening because even when negative, these do not rule out past exposure); rheumatoid factor; antinuclear
antibody; erythrocyte sedimentation rate (level of 100 indicates polyarteritis nodosa or temporal arteritis); antineutrophil
cytoplasmic antibody (ANCA) panel to rule out Wegener’s granulomatosis; Chemistry 20 (gouty scleritis); viral serology
sometimes helpful; urinalysis detects nephritis or nephritic syndrome related to renal vasculitis; chest or joint x-ray to detect
sarcoidosis or inflammatory arthritis
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| Ultrasonography (US), computed tomography (CT), and biopsy: US helpful in posterior scleritis; orbital CT used for posterior
disease; biopsy detects postoperative infectious scleritis but aggravates inflammatory scleritis; routine medical
consult not necessary; US detects serous retinal detachment and variable scleral edema; B-scan US provides more data;
orbital CT shows scleral thickening; contrast uptake shows active inflammation and elucidates orbital myositis, posterior
scleritis, and orbital pseudotumor (similar diseases); electron micrographs—provide cellular information (eg,
metabolically active scleral cells, extra- and intracellular collagen degradation, collagen phagocytosis)
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| Complications: uveitis; glaucoma due to outflow congestion, increased episcleral venous pressure, angle closure,
neovascular causes, or steroid use; cataracts; keratitis, especially PUK; retinal detachment; retinal pigment epithelium/
choroidal detachment; nerve and macular edema in posterior and long-standing anterior scleritis cause cranial nerve palsies;
scleral thinning; rarely perforation
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| Topical: speaker opposed to topical therapy for scleritis, topical corticosteroid use, or nonsteroidal anti-inflammatory
drugs (NSAIDs) in episcleritis; topical corticosteroids for uveitis and glaucoma; harmful in PUK (instead use systemic
corticosteroids)
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| Systemic: oral NSAIDs (eg, piroxicam) treatment of choice for chronic episcleritis; 20-mg dose tapered to 10 mg with
food; practical approach; oral corticosteroids (60-80 mg of prednisone) to treat scleritis; abolishes pain quickly; difficult
to taper; systemic antimetabolites (eg, methotrexate, azathioprine, cyclosporine) and newer-generation drugs (eg,
infliximab [Remicade], mycophenolate mofetil [MMF; CellCept]) may have future role
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| “Express lane” approach: 0.05 to 0.1 mL triamcinolone injection with 30-gauge needle near inflammation site; no systemic
side effects; monitor for glaucoma; may require repeating in 2 to 3 mo
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| Surgical: eg, young patient, active lifestyle has scleral thinning or risk for perforation; scleral or corneal homograft; fascia
lata or periosteal autografts provide less rejection and inflammation, easier to manipulate; difficult to dissect conjunctiva
from choroid without bleeding or perforation; place graft, sew with 10.0 vicryl or nylon sutures; replace
conjunctiva (running or mattress suture); cover graft completely to avoid necrosis and inflammation
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| Prognosis: diffuse disease relatively benign; nodular necrotizing disease worse; monitor patients for surgical and systemic
complications; high rate of systemic disease with nodular conditions; systemic disease must be treated
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| UVEITIS AND PARS PLANITIS
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| Intermediate uveitis: International Uveitis Study Group definition—inflammation centered in anterior vitreous, pars
plana ciliaris, and peripheral retina; associated diseases—multiple sclerosis (MS; especially in older patients); sarcoidosis;
human T-lymphotropic virus type 1 (HTLV-1) infection in endemic areas; Whipple’s disease; retinitis pigmentosa;
HTLV-1 infections—patients from Japan, Central Asia, Caribbean, and South America; acute onset, unilateral, more anterior
chamber reaction, keratic precipitates (KP), posterior vasculitis (not common in pars planitis [PP]); self-limiting;
good response to steroids; some relapse; PP—most common form; idiopathic intermediate uveitis of young people, accompanied
by pars plana exudate (“snowbank”); incidence 4% to 15% in uveitis; approximately equally distributed between
males and females; peaks in late first decade (ages 4-18 yr; two thirds boys) and late 20s (ages 20-40 yr; two thirds
women); bilateral in >90%; speaker believes always bilateral; asymmetric; worldwide, 5% to 15% of patients with uveitis
have PP
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| Segment signs in PP: anterior—quiet eye with mild anterior chamber reaction; occasional fine or mutton-fat KP or
posterior synechiae (especially early on); Khodadoust line visible; appears as discrete corneal endothelial rejection line;
anteriorly no KP, no findings; posteriorly, mutton-fat KP and corneal edema; occasional trabecular precipitates lead to peripheral
anterior synechiae in “fair number” of cases; posterior—vitreous cells sine qua non; clumps of inflammatory
cells (vitreous “snowballs”); periphlebitis common (hard to see; near snowbank and inferior retinal periphery); cystoid
macular edema (CME) common (most common cause of permanent vision loss in PP patients); “hot nerve” and possible
subtle vasculitis on fluorescein stain; in study (Henderly), 15% of uveitis patients had PP (10% with classic form [PP with
snowbank] and 5% with variant form [classic findings without snowbank])
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| Complications of PP: cataracts; children have disease for 3 to 15 yr; CME common; anterior and posterior synechiae;
retinal detachment; glaucoma less common; neovascularization
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| Differential diagnosis of PP: sarcoidosis—usually more granulomatous, anterior segment findings, more mutton-fat
KP; Fuchs heterochromic iridocyclitis—patients rarely need treatment; stellate KP on cornea, usually unilateral; posterior
spillover—more anterior segment signs, history of pain and photophobia; Irvine-Gass syndrome—postsurgical
patients; retinitis—retinal signs; amyloidosis—uncommonly presents as PP; lung and liver amyloid infiltrates; difficult
diagnosis; Whipple’s disease—gastrointestinal symptoms; MS—some clinicians suggest magnetic resonance imaging
(MRI) for older PP patients; speaker disagrees (perform neurologic review of symptoms, follow up with MRI, consult
neurologist as needed); masquerade syndromes—important; in unilateral PP, patients have syndrome or tumor; in elderly
patients with PP or in >35-yr-old patients with new-onset PP, consider large cell lymphoma or other diseases
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| Work-up for PP: not needed in patient with first episode of unilateral anterior uveitis; others with cells in eyes need
work-up; CBC with differential, chest x-ray (for sarcoidosis), and FTA; patients with history of chronic nonproductive
cough and shortness of breath require chest CT or measurement of angiotensin-converting enzyme (ACE); cranial MRI
for MS patients; Lyme serology in endemic areas (eg, Northeastern states); medical consultation for masquerade syndromes;
high suspicion with unilateral disease; relatively benign when treated appropriately; classic PP—more CME,
more severe vitritis and vasculitis, worse vision; overall good prognosis
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| Etiology of PP: not well understood; speaker suspects autoimmune response against vitreous (not confirmed); retinal degeneration;
possible unidentified infectious agent; possible inherited tendency; histopathology—uvea shows mild round
cell and lymphocytic infiltrates; retina displays traction from snowbank (traction retinal detachment), and lymphocytic cuffing
of retinal vasculature; snowbank consists of fibroglial and fibrous tissue, condensed inflammatory tissue, mononuclear
cell infiltrate (always vascularized); T lymphocytes, few B cells
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| Treatment: Kaplan’s 4-step approach—1) corticosteroids; oral prednisone in divided doses (1 mg/kg; 5-10 mg tid) for
young children; single morning dose in adults prevents insomnia; sub-Tenon’s injection option; 2) cryotherapy (laser) to
snowbank, to peripheral retina posteriorly; 3) pars plana vitrectomy effective but invasive; cataract development; 4) cytotoxic
immunosuppressive medications effective; speaker prefers methotrexate, due to remissions; cyclosporine effective,
but no remission; do not use routinely; 5) Food and Drug Administration approved fluocinolone implant (Retisert) in
2006
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| Therapeutic cautions and take-home message: be patient; regardless of therapy, vision improves slowly; treat using
4-step approach; communicate with parents; wait 4 to 6 mo before determining failure of steroid therapy; adjust immunosuppressant
doses; do not treat neovascularization initially with panretinal photocoagulation (PRP; treat with anti-
inflammatory agents; can use PRP if recalcitrant); keep eye quiet (with corticosteroids or other treatment) for 3 mo before
performing cataract surgery; use 3-piece lens; speaker always arranges for pars plana vitrectomy to be performed at same
time (makes sense to remove vitreous, probable seat of inflammation); intravitreal corticosteroids useful; acrylic lenses
preferred, polymethylmethacrylate (PMMA) lenses acceptable; speaker avoids silicone in patients with inflammation;
speaker suggests starting CME treatment early (20/25 vision); do not treat isolated floaters; most patients do well with
modern phacoemulsification, intraocular lens, pars plana vitrectomy surgeries (phaco/IOL/PPV) and filtering/shunt surgery
as needed
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Suggested Reading
Androudi S et al: Safety and efficacy of intravitreal triamcinolone acetonide for uveitic macular edema. Ocul Immunol
Inflamm 13:205, 2005; Atchia II et al: Rheumatoid arthritis-associated necrotizing scleritis and peripheral ulcerative
keratitis treated successfully with infliximab. J Clin Rheumatol 12:291, 2006; Choi JY et al: Primary intraocular lymphoma:
A review. Semin Ophthalmol. 21:125, 2006; Feiz V, Redline DE: Infectious scleritis after pars plana vitrectomy
because of methicillin-resistant Staphylococcus aureus resistant to fourth-generation fluoroquinolones. Cornea 26:238, 2007;
Foster CS: Diagnosis and treatment of juvenile idiopathic arthritis-associated uveitis. Curr Opin Ophthalmol 14:395,
2003; Galor A et al: Differential effectiveness of etanercept and infliximab in the treatment of ocular inflammation. Ophthalmology
113:2317, 2006 Harper SL et al: Wegener's granulomatosis: the relationship between ocular and systemic
disease. J Rheumatol 28:1025, 2001; Henderly DE et al: The significance of the pars plana exudate in pars planitis. Am J
Ophthalmol 15:669, 1987; Jabs DA et al: Standardization of uveitis nomenclature for reporting clinical data. Results of
the First International Workshop. Am J Ophthalmol 140:509, 2005; Jabs DA et al: Guidelines for the use of immunosuppressive
drugs in patients with ocular inflammatory disorders: recommendations of an expert panel. Am J Ophthalmol
130:492, 2000; Kafkala C et al: Masquerade scleritis. Ocul Immunol Inflamm 13:479, 2005; Kim EC, Foster CS:
Immunomodulatory therapy for the treatment of ocular inflammatory disease: evidence-based medicine recommendations for
use. Int Ophthalmol Clin 46:141, 2006; Kranias G et al: Bilateral atypical nodular posterior scleritis. Eur J Ophthalmol
16:614, 2006; Lim L et al: Biologic therapies for inflammatory eye disease. Clin Experiment Ophthalmol 34:365, 2006;
Meldrum ML et al: Collagen vascular diseases: cutaneous manifestations in ophthalmology. Ophthal Plast Reconstr
Surg 16:459, 2000; Ooi KG et al: Necrotising anterior scleritis in a late-onset rheumatoid arthritis (LORA) patient. Ocul
Immunol Inflamm 15:33, 2007; Pakrou N et al: Wegener's granulomatosis: ophthalmic manifestations and management.
Semin Arthritis Rheum 35:284, 2006; Perez VL et al: Ocular manifestations and concepts of systemic vasculitides. Surv
Ophthalmol 49:399, 2004; Perez VL, Foster CS: Uveitis with neurological manifestations. Int Ophthalmol Clin 41:41,
2001; Rojas B et al: Medical treatment of macular edema in patients with uveitis. Doc Ophthalmol 97:399, 1999; Smith
RJ, Maloney RK: Laser in situ keratomileusis in patients with autoimmune diseases. J Cataract Refract Surg 32:1292,
2006; Stavrou P et al: Pars plana vitrectomy in patients with intermediate uveitis. Ocul Immunol Inflamm 9:141, 2001;
Strauss EC, Foster CS: Atopic ocular disease. Ophthalmol Clin North Am 15:1, 2002; Su CY et al: Immunologic
and clinical manifestations of infectious scleritis after pterygium excision. Cornea 25:663, 2006; Zein G et al: Multiple
sclerosis-associated uveitis. Ocul Immunol Inflamm 12:137, 2004
Educational Objectives
| The goal of this program is to improve the diagnosis and management of scleritis, pars planitis, and uveitis. After
hearing and assimilating this program, the clinician will be better able to:
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| 1. Differentiate scleritis from episcleritis.
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| 2. Integrate appropriate work-ups for scleritis and recurrent episcleritis.
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| 3. Choose the most effective treatment options for scleritis and recurrent episcleritis.
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| 4. Recognize classic and atypical signs and symptoms of pars planitis.
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| 5. Utilize the Kaplan 4-step approach for treating pars planitis.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose relevant
financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts
were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial
interest. For this program, the speaker reported nothing to disclose.
Acknowledgements
Dr. Zimmerman addressed the 28th Annual Scientific Meeting, held February 23, 2007, in Salt Lake City, UT, and sponsored
by the Utah Ophthalmology Society. The Audio-Digest Foundation thanks Dr. Zimmerman and the Utah Ophthalmology
Society for their cooperation in the production of this program.
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