Uveitis Flashcards
Which IOP lowering class of drugs would you want to avoid when treating a steroid-responder in the management of uveitis?
prostaglandins
What are the 3 mainstays of treatment for most uveitis?
Corticosteroids, cycloplegics, and treating the underlying cause
Which steroid drops are good choices for anterior uveitis?
Pred acetate susp. (generic), 1% Pred Forte (brand), and Durezol
What are the benefits and considerations for using Durezol?
Do not have to shake so is simpler for the patient, QID dosing instead of q1hr, stronger, $200-300, can be more likely to increase IOP
What are the benefits and considerations for using Pred Forte?
also expensive, have to shake, not as strong as Durezol, or as likely to increase IOP, dosing q1-2hr
When would you consider using a weaker steroid for uveitis?
for mild anterior uveitis, and if the patient is a steroid responder
General guidelines for steroid dosing for uveitis
hit it hard! q1-2hr for 1-2wks, may need loading dose, maintain dose until AC is free of cells
How do you taper in uveitis?
SLOW taper is very important, but can be very variable. Adjust based on severity/propensity for recurrence/length of tx
ex. QID x1wk, TID x1wk, BID x1wk, QD x1wk, stop
Instructions on the Rx for steroid for uveitis
ex. Pred Forte, 1 gtt OD q1hr while awake, taper as directed, 0 refills, NO SUBSTITUTION
What is a pulse dose?
circumstances when steroids are used for a short period of time and don’t require a taper, such as for corneal/conjunctival disease such as dry eye or episcleritis. Infrequently used in treating uveitis
What are the ocular side effects for topical steroids?
increased IOP, PSC, increased risk of bacterial/viral infection
What are some systemic side effects of steroids?
increased serum glucose, hyperlipidemia, hypertension, sodium and water retention edema, centripetal obesity, buffalo hump, impaired wound healing, suppression of hypothalamic-pituitary-adrenal system, secondary infections, osteoporosis, psychiatric, gastritis, etc.
What purpose do cycloplegics play in treating uveitis?
Cycloplegics prevent ciliary spasm, reducing symptoms and improving comfort of the patient, while stabiling blood aqueous barrier, and preventing formation of posterior synechiae
Which cycloplegics are the best for uveitis?
1 is homatropine 5%, can be hard to find though, then atropine, or cyclopentolate.
Scopolamine and tropicamide are not used for uveitis.
What is a contraindication that should be considered when prescribing a cycloplegic for uveitis?
narrow angles! and also the stronger cycloplegics are contraindicated in patients with Down syndrome (try to use the weakest ones if required)
What drop do we use to break posterior iris synechiae?
10% phenylephrine, in office only
What are other considerations for a uveitis exam?
DFE for every anterior uveitis patient same day is required! Have to look for signs of intermediate and posterior uveitis
When is the first follow up for uveitis patients?
RTC 1-3 days, not much improvement yet, and don’t release the patient once you start tapering the steroid as rebound inflammation may occur
What can we do for prophylaxis for uveitis?
Pred Forte may be used in a low dose indefinitely for those with frequent recurrence or chronic disease. 1 drop Pred Forte QD or every other day. Or small dose 10-20mg prednisone
When would you try oral/intra-/peri-ocular injected steroids?
when pred forte isn’t enough in moderate to severe non-infectious inflammation, posterior seg involvement (CME), or when the anterior uveitis is resistant to topicals
What is the usual choice and dose for oral steroids for uveitis?
0.5-1.5 mg/kg/day followed by taper (about 40-120 mg daily)
What are the added side effects for steroids injected periocularly (sub-tenon or sub-conj)?
sub-conj heme, conj/Tenon scarring, scleral perforation, abscess/infection
What steroids are used IVT for uveitis?
IVT triamcinolone (IVTA), Triescence or Kenalog
effective for 3 months in non-vitrectomized eyes
What are some medium to long-duration implanted steroids?
Ozurdex (dexamethasone)
Retisert, Yutiq, Iluvien (flucinolone acetonide)
What are the added side effects for the medium to long-duration implanted steroid options?
higher likelihood of IOP spike, RD, vitreous hemorrhage, endophthalmitis, accelerated cataract formation
Ozurdex
FDA approved for posterior uveitis, biodegradable, injected into vitreous, effective for 3-6mo
Retisert
fluocinolone acetonide implantable device, FDA approved for posterior uveitis, non-biodegradable, sutured to sclera, effective for 2.5 years, higher sustained daily dose and others
Yutiq
fluocinolone acetonide insert, non-biodegradable, injected into vitreous, effective for 3 years, FDA approved for non-infectious posterior uveitis, 2019
Iluvien
fluocinolone acetonide insert, non-biodegradable, injected into vitreous, effective for 3 years, FDA approved for DME, but may be used off-label in uveitis
Immunosuppressive agents used in uveitis
biologics - infliximab, adalimumab, etanercept
antimetabolites - methotrexate, azathioprine, mycophenolate mofetil
T-cell inhibitors, alkylating agents
Humira (Adalimumab)
TNFa inhibitor, SQ injection, the only systemic non-steroid med FDA approved for non-infectious uveitis (intermediate, posterior, and pan) 2016. typically used alongside steroid therapy for chronic inflammation
for RA, JIA and HLA B27 diseases
Treatments for infectious uveitis
topical/IVT/po/IV antibiotics, antivirals, antiprotozoans, antifungals, etc.
Surgical managment for uveitis
unresponsive to medical tx, or for secondary complications like CME, ERM, RD, hypotony, glaucoma, cataract, vitreous opacification, lens-induced uveitis, endophthalmitis, or for placement of drug delivery system
Anterior uveitis symptoms
hyperemia, ocular pain (unique dull pain), photophobia, blurred vision, headache, (rarely asymptomatic)
Intermediate/posterior uveitis symptoms
possibly asymptomatic, blurred vision, floaters
Case history questions for uveitis
Laterality, timing/nature of onset, associated symptoms (positive and negative), aggravating/relieving factors, previous events
uveitis classification for onset
acute: sudden onset <6wks duration
chronic: persistent relapse in <3mo after d/c tx
recurrent: repeated episodes separated by periods of inactivity without tx >3mo in duration
granulomatous uveitis classification
presence of granulomatous signs: mutton fat KPs, Bussaca iris nodules, choroidal granulomas
due to granulomatous disease
What are the granulomatous diseases that can cause uveitis? (the ones that are capable of causing both gran and non-gran)
Lens-induced, VKH, Sympathetic ophthalmia, Sarcoidosis, Herpes, Intraocular foreign body, TB, Syphilis
What are the conditions that can cause uveitis but only non-granulomatous?
Toxoplasmosis, Behcets, Traumatic, MS, Onchocerciasis, Toxocariasis, TINU, JIA, Drug-induced, UGH, HLA-B27 diseases, Bartonella, TASS, Glaucomatocyclitic Crisis, Fuchs heterochromatic iridocyclitis, and Lyme disease
When other structures of the eye are involved with anterior uveitis we can refer to them as
Keratouveitis, or sclerouveitis
What is the most common form of uveitis (which area in eye)?
Anterior uveitis, includes iritis, iridocyclitis, and trabeculitis
Common signs of anterior uveitis
conjunctival injection, AC cells and flare, KPs, iris synechiae, hypopyon, iris nodules
Hypopyon
layering/settling of WBCs and protein in inferior AC, grading is based on height (ex. 2mm)
What are the 3 types of iris synechiae?
Anterior (iris to cornea), posterior (iris to lens), and peripheral anterior (PAS - iris to TM or peripheral cornea)
What secondary complication happens with PAS?
angle closure glaucoma
What secondary complications can happen with posterior synechiae?
pupillary block glaucoma and iris bombe
What is the difference between Busacca and Koeppe nodules?
Koeppe nodules are on the iris margin and are non-granulomatous, while Busacca iris nodules can be found anywhere on iris surface and are pathognomonic for granulomatous disease
What are the signs of intermediate uveitis?
vitritis, pars planitis: vitreous cells, haze, snowbanking
(sometimes cells are spillover from AC)
What are the possible signs of posterior uveitis
Retinitis/choroiditis: infiltrates, RPE atrophy, window defects, RPE hyperplasia, subretinal fibrosis, optic disc edema, CME, SRD, TRD, retinal vasculitis, angiitis, arteritis, periphlebitis, exudates
Panuveitis
inflammation in several ocular structures (AC and vitreous/retina/choroid)
must rule out infectious endophthalmitis!
Approximately how much of NGAU cases (non-traumatic) are idiopathic (no associated systemic or ocular condition)?
half
Uveitis is more likely to be systemic disease-mediated if
bilateral, recurrent, intermediate/posterior seg involved, granulomatous, pediatric, or does not respond to standard therapy
Sensitivity definition
the proportion of positives that are correctly labeled as such
Specificity definition
the proportion of negatives that are correctly labeled as such
Sensitivity formula (not PPV)
Sensitivity = TP/P = TP/(TP+FN)
Positive Predictive Value
PPV = TP/(TP+FP)
Specificity formula (not NPV)
Specificity = TN/N = TN/(TN+FP)
Negative Predictive Value
NPV = TN/(TN+FN)
CBC w/diff
combines several tests of the hematologic system, inexpensive, fast, common screening of RBCs, WBCs and platelets
Neutrophils/PMNs can show:
acute bacterial infection and trauma
Basophils and Eosinophils can show:
allergic or parasitic infection
Lymphocytes on bloodwork can show:
chronic bacterial or acute viral infections
ESR
sensitive but not specific, test for acute inflammation, injury and infection
norms for men is age/2 and for women is (age+10)/2
values >30 are typically abnormal
CRP
non-specific inflammation marker, typically should be <1.0 mg/dL
CMP
14 tests: glucose, calcium, albumin, total protein, sodium, potassium, CO2, chloride, BUN, creatinine, ALP, ALT, AST liver enzymes, bilirubin
ELISA
enzyme-linked immunosorbent assay used to detect organisms that aren’t easily cultured
HIV, toxo, TB, cocci, VZV, HSV, Lyme, WNV, HBV
IgM on ELISA indicates?
recent/active infection
IgG in ELISA indicates?
previous infection
What are the seronegative spondyloarthropathies associated with causing anterior uveitis?
Psoriatic arthritis, Ankylosing spondylitis, IBD (Crohn’s and Ulcerative Cholitis), Reactive arthritis, Non-specific HLA-B27 disease
HLA-B27+ percentages:
Highest prevalence in Whites and northern Europeans (~8%)
Between 32-50% of all cases of anterior uveitis are HLA-B27+
6% of the US population is HLA-B27+
88-90% of those w/ankylosing spondylitis are HLA-B27+
8% of caucasian have the gene, of these 2% will eventually get spondylitis
Systemic features of seronegative spondyloarthropathies
ocular inflammation (anterior uveitis), sacroiliitis with or without spondylitis on x-ray, inflammatroy asymmetric peripheral arthritis primarily in lower limbs, RF negative, ANA negative, strong association with HLA-B27, mucocutaneous lesions, rare cardiac disease
Ankylosing spondylitis
most common cause of uveitis among HLA-B27 diseases, young 15-40yo M>F, lower back pain, chronic arthritis of spine and sacroiliac joints, “bamboo spine” deformity
What type of uveitis often presents due to ankylosing spondylitis?
unilateral, alternating, recurrent acute anterior uveitis
DX and TX for ankylosing spondylitis
DX: SI x-ray, ESR and CRP may also be elevated
TX: oral steroid and mydriatic, referral to rheumatology, good repsonse to NSAIDs, also immunosuppressive therapy, physical therapy
Psoriatic arthritis
causes NGAU, conjunctivitis, is in 1-2% of the caucasian population
DX: clinical suspicion, rheumatology consult
TX: corticosteroid, mydriatics, NSAIDs, other immunosuppressive therapy, physical therapy
Reactive arthritis
young 15-40yo M>F, systemic triad: urethritis, arthritis, mucocutaneous (mouth and genital) lesions. Ocular: conjunctivitis and NGAU
IBD
GI symptoms and arthritis that waxes and wanes, anterior uveitis, episcleritis
DX: GI consult, colonoscopy w/biopsy
IBD tx
Ocular tx - steroid and mydriatic
Systemic tx - immunosuppressive therapy (be careful with NSAIDs as can exacerbate GI symptoms), surgical excision of inflamed bowel, physical therapy
Sarcoidosis
multisystem granulomatous disease, non-caseating (skin, eye, lung, lymph node involvement), african descent, F>M, adults, mortality of 3-10%
Symptoms: SOB, fever, fatigue, pulmonary granulomas, skin lesions
Ocular: dry eye, eyelid/orbital granulomas, uveitis (often anterior granulomatous, and often bilateral)
Sarcoidosis testing/dx
elevated serum ACE, elevated serum/urine calcium, abnormal CXR: bilateral hilar lymphadenopathy, abnormal gallium scan (panda and lambda sign), definitive dx w/biopsy showing non-caseating granulomas
Sarcoidosis tx
ocular tx: steroid, mydriatic, ATs for dry eye, oculoplastics consult if granulomas affecting lids
systemic tx: steroids and other immunosuppressive therapy
pulmonology, dermatology, etc.
VKH
primarily in darker complexions, 20-40yo, slight F>M, an autoimmune disorder involving multiple systems (ocular, auditory, nervous, and integumentary), often HLA-B22+
VKH symptoms and ocular presentation
Ocular: diffuse granulomatous uveitis w/SRD, reccurence common, starts as choroiditis and gets worse, to bilateral panuveitis and SRD, “sunset glow” fundus
Prodromal phase: fever, HA, neck stiffness, vertigo
Systemic: tinnitus, vitiligo, poliosis, alopecia
Behcet disease
relapsing vasculitis/inflammatory disorder, triad: ocular inflammation, oral/genital aphthous ulcers (painful), skin lesions
Asian M>F, often HLA-B51+
Tx: systemic steroids limited so need to use other immunomodulatory therapy
Behcet disease ocular manifestations
Anterior uveitis with hypopyon, often recurrent but not chronic
also possible: retinal vasculitis, retinal hemorrhages, and vein occlusions, mac edema, optic disc edema
OIS
characterized by lack of blood flow to the eye, thrombotic in carotid arteries, >50yo with new-onset anterior uveitis, M>F, mild AC reaction (20% of the time), dot and blot hemes, amaurosis fugax, ischemia eventually, TIAs and CVAs
OIS tx
OIS uveitis is non-responsive to steroids
can do a carotid endarterectomy when benefit outweighs risks
Intermediate uveitis DDx
Idiopathic, sarcoidosis, syphilis, Lyme, cat scratch disease, MS, intraocular lymphoma
MS associated intermediate uveitis
Often with pars plana snowbanking, demyelinating disease of CNS
Dx with MRI
1% of pts with MS will have uveitis
1% of uveitis pts will have MS
What percent of all uveitis cases are pediatric?
6%
Most pediatric uveitis is:
anterior, non-infectious, due to JIA (95% of non infectious pediatric cases are JIA or other spondyloarthropathies)
JIA
Chronic bilateral NGAU (recurrent, often asymptomatic!)
oligoarticular JIA at highest risk, RF negative, make up 95% of childhood anterior uveitis, F>M, age 4-16
can present with band keratopathy, and irregular pupil due to posterior synechiae
pediatric uveitis prognosis with the presence of synechiae
(+) PS: 58% ended up 20/200 or worse
(-) PS: 3% ended up 20/200 or worse
ANA+, younger age, and uveitis preceding arthritis is also associated with poorer outcomes
Managing JIA uveitis
ANY CHILD with uveitis warrants rheumatology consult
pts with chronic anterior uveitis should be seen at least q3mo
TINU: Tubulointerstitial Nephritis and Uveitis Syndrome
Bilateral NGAU
possible cell-mediated hypersensitivity, F>M, children and young adults, rare
systemic: high ESR, proteinuria, increased urinary beta 2 microglobulin, and serum creatinine
TINU dx and tx
DX: renal biopsy, nephrology, pediatrics, urinary beta 2 microglobulin
TX: topical steroid/cycloplegic, systemic steroids/immunomodulators
recurrence in >50% of cases with uveitis
Glaucomatocyclitic Crisis
20-50yo, M=F, recurrent, unilateral trabeculitis, mild NGAU, extremely high IOP, mild discomfort, diagnosis of exclusion, tx with IOP lowering drops, corticosteroids QID
Fuchs heterochromic iridocyclitis
young adults, M=F, idiopathic, chronic mild unilateral NGAU, stellate KP, smooth iris, heterochromia in later stages, unilateral PSC
Lens-induced uveitis
auto-immune type reaction to excessive leakage of lens material, accompanied by ocular hypertension, r/o endophthalmitis! and sympathetic ophthalmia
UGH - Uveitis Glaucoma Hyphema Syndrome
triad of anterior uveitis, hyphema, and increased IOP, can be caused by AC-IOL friction against iris or from iris implants
What do you assume hyphema is from if no trauma/surgical history?
assume NVI
considerations when a patient has hyphema
wait until cleared before doing gonio to look for angle recession, limit physical activity, sleep w/head elevated, manage any ocular HTN, sx management if non-clearing, uncontrolled IOP, or corneal staining
Traumatic uveitis
20% of all iritis, young M>F, NGAU
Vossius ring, dx: h/o of recent injury
tx: cycloplegic, pred acetate 1% QID usually sufficient
Vossius ring
pigment on anterior capsule of lens due to severe blunt trauma
mimics pigment due to posterior synechiae
Endophthalmitis symptoms
redness, sensitivity to light, vision loss, pain (RSVP)
INFECTIOUS!
managing endophthalmitis
treat empirically, don’t wait for confirmation, IVT antibiotics
presenting VA is most important prognostic indicator
review importance of lid hygiene with patients before surgery!
TASS
rare sterile inflammation in the immediate post-op period (12-24hr) after cataract sx
tx: topical steroid once endophthalmitis is ruled out, otherwise treat as infectious
Sympathetic ophthalmia
rare inflammatory condition in which one eye with penetrating injury or surgery incites an inflammatory response in the other eye. presents as a granulomatous non-necrotizing inflammation in uveal tract of both eyes (bilateral panuveitis)
Drug-induced uveitis
bisphosphonates (Bonia and Fosamax), oral fluoroquinolones (moxi), rifabutin, systemic sulfonamides, cidofovir, intradermal vaccines (influenza, hepatitis B, BCG)
Immune recovery uveitis
immune response after HIV+ individuals start HAART therapy and CD4+ T-lymphocytes rise. Low-grade vitritis with or without papillitis, CME, ERM
Uveitis in pregnancy/breastfeeding
pred forte is not tested in human trials but is expected to be low risk for the fetus due to limited systemic absorption
when in doubt call the OB
Acute Uveitis (causes summary)
Traumatic, ankylosis spondylitis
(not complete)
Chronic uveitis (causes summary)
Fuchs heterochromic iridocyclitis, JIA
(not complete)
Bilateral uveitis (causes summary)
TINU, JIA, sarcoidosis
(not complete)
