White Dot Syndromes & Uveitis Flashcards
Quenching on FA
Birdshot
MEWDS
- poorly understood, idiopathic inflammatory condition of the inner choroid and/or outer retina.
- u/L in younger myopic females
Si/Sx: central vision loss, enlarged blind spot, and photopsias.
- hallmark features = short-lived white dots usually lasting from days to a week after visual symptoms begin, permanent macular pigment stippling, macular wreath-like punctuate hyperfluorescence on fluorescein angiography [smaller hyerF dots make it up], and mild disc edema in some cases.
- SD-OCT: non-specific but DIAGNOSTIC OF MEWDS = disruption of IS/OS junction and RPE. disruption of the usual contour of these layers without evidence of retinal edema. Present even s/p white dots have resolved.
Similar changes can be seen in AZOOR, commotio retinae, and solar retinopathy.
Photopsias
AZOOR, MEWDS, idiopathic enlarged blind spot
Photopsias = prominent feature in a young patient with central vision loss should raise suspicion for these conditions.
Other causes of photopsias associated with vision loss are often short lasting (migraine), have prominent exam findings (retinal detachment or tears), or don’t typically present in a young patient (cancer-associated retinopathy and melanoma-associated retinopathy).
APMPPE
Block early stain late
Birdshot
vitiliginous chorioretinitis
- disease typically occurs in women
- always has some vitritis, has retinal lesions that are more numerous in the NASAL retina
- usually bilateral.
-peculiar FA phenomenon of “quenching” can occur in this disease whereby the dye disappears quickly from the retinal circulation
AZOOR
Acute zonal occult outer retinopathy (AZOOR) is often considered among the white dot syndromes and classically presents with acute onset of photopsias and an enlarged blind spot scotoma. Initially fundus findings are often absent but over time these patients develop retinal pigment epithelium atrophy extending off of the optic nerve and corresponding perfectly to their scotoma.
DFE: ZONAL REGIONS OF ATROPHY &HYPERPIGMENTATION (RPE clumping) along ON/temporal vascular arcades.
VF: defects match RPE atrophy region. Almost always has VF emanate from blind spot.
FA: large patches of “window defect” hyperfluorescence 2/2 increased transmission of choroidal fluorescence 2/2 loss of normal RPE overlying choroid
Idiopathic blind spot enlargement syndromes
“waste basket” - MEWDS and AZOOR
Look for fundus findings.
Normal DFE = Idiopathic blind spot enlargement syndrome
DFE w/temporal retinal whitening (days-weeks) with “granularity” of the macular RPE (permanent change) = MEWDS (MEWDS resolves usually w/in 3 mo)
AZOOR > 75% prominent photopsias. 60% of time is u/L.
Unlike MEWDS, AZOOR can involve the fellow eye in 60% of u/L cases
Serpiginous
blockage in the early frames, but early hyperfluorescence at the edges of the lesions
DDx: APMPPE (acute posterior multifocal placoid pigment epitheliopathy) since both can present with large placoid yellowish lesions at the level of the RPE. BUT APMPPE lesions resolve spontaneously over a few weeks and visual prognosis is generally good.
In select cases, treatment with immunosuppressives (e.g. mycophenylate, cyclosporine, azathioprine, and prednisone) may induce remission.
According to the BCSC, CNV only rarely occurs at the margin of an area of chorioretinal atrophy.
PIC (punctate inner choroidopathy)
- OCT: focal loss of IS/OS photoreceptor junction and RPE at fovea
- FA: window/staining defects 2/2 loss of these layers
- MYOPIC females (90%) 18-40 yo
- DFE: yellow-white chorioretinal lesions 100-300 um diameter at level of inner choroid and RPE. Found OU in 80% of cases. Progress to atrophic scars –> halo of depigmentation which often appears punched out. Subretinal neovascular membranes occur in at least 1/3 of cases.
PIC and MCP = spectrum of same disease
CNV = MCC permanent vision loss in PIC
no systemic association
OHS vs. MCP
Both have punched out lesions
However, OHS has NO VITRITIS, as opposed to 90% MCP pts with vitritis.
MCP (multifocal choroiditis and panuveitis)
poor Px (like serpiginous. MC in females, affects OU
Type I
Anaphylactic or atopic
mast cells and histamine
Example? Allergic conjunctivitis seasonal component Atopic conjunctivitis environmental triggers less seasonal ezcema, asthma Anaphylaxis
Type II
Cytotoxic
Foreign or autoantigens
Example?
OCP (IgA deposits in BM)
Mooren Ulcer
Type III
Immune-complex reaction
Example? Scleritis Vasculitis Phacoanaphylaxis Stevens-Johnson syndrome
Type IV
Delayed hypersensitivity
T Cell mediated
Example? Contact dermatitis Phlyctenulosis Corneal graft rejection Sarcoid, TB
Type V
Stimulating antibody
Example?
Graves’ disease
Giant cells (3 types)
1) Langhans
Nuclei in periphery
What disease?
TB, sarcoidosis
2) Touton
mid-peripheral ring of nuceli
What disease?
JXG, chalazion, xanthelasma
3) Foreign Body
Randomly-distributed nuceli
Anterior scleritis
Female > male, bilateral (50%)
Systemic associations? (50%)
RA, SLE, PAN, Wegener, relapsing polychondritis, Reiter
Syphilis, TB, VZV, Lyme, Bartonella
3 Types? Diffuse (40%) Nodular (40%) Necrotizing (15%) Most destructive
Path?
Palisading histiocytes, multinucleated giant cells, scleral necrosis
Scleromalacia perforans?
Frequent in RA
Painless, minimal inflammation
Thin sclera with herniating uvea
Posterior scleritis (2%)
Symptoms?
proptosis, restricted eye motility
Clinical Signs?
Choroidal folds, exudative RD, papilledema, ACG from choroidal thickening, lower eyelid retraction
Diagnostic testing?
Thickened posterior sclera on U/S (“T” sign), CT, or MRI
Systemic association?
None
Treatment?
Topical or oral steroids
NO subconj or subtenon steroids (can cause scleral necrosis)
Immunosupression: MTX, cyclosporine, cyclophosphamide
Reiter syndrome
Young adult males
HLA-B27
Triggered by infection (usu. GI)
Dysentery, chlamydia, ureaplasma, shigella, salmonella, yersinia
Triad? Can’t see, can’t pee, can’t climb a tree
Conjunctivitis (+/- iritis)
Urethritis
Polyarthritis
2 additional criteria?
Keratoderma blennorrhagicum: Rash on palms and soles of feet
Balanitis: rash on distal penis
Minor criteria?
Plantar fasciitis, achilles tendinitis, nail-bed pitting, palate ulcers, tongue ulcers
Other seronegative dx w/ uveitis?
Ankylosing spondylitis
Psoriatic arthritis
Ulcerative colitis»_space; Crohn’s disease
Uveitis:
How long after quiescent for PK?
How long after quiescent to CE?
CE = 3 mo PK = 6 mo
Wegener Granulomatosis
Systemic granulomatous vasculitis
Ocular findings? Scleritis (25%) Posterior scleritis with exudative RD Recurring orbital pseudotumor Proptosis Retinal vasculitis, retinitis
Systemic findings?
Lung & renal involvement
Sinusitis, epistaxis
Saddle-nose deformity
Diagnosis?
cANCA (95% sensitive, 88% specific)
Tissue biopsy
Treatment?
Immunosuppression (cyclophosphamide), TMP-SMX (bactrim)
80% mortality rate if untreated
Juvenile Idiopathic Arthritis
3 types? Pauciarticular (2 types ?) Type 1: early-onset 80% girls RF-, ANA+ (60%), HLA-B27- Chronic uveitis (30%)
Type 2: late-onset
90% boys
RF-, ANA-, HLA-B27+ (75%)
Acute uveitis (15%)
=== Polyarticular Uveitis rare 85% girls; 40% of JRA; 75% RF- ====
Still’s disease
Uveitis rare; systemic JRA w/ high fever, rash, organomegaly
60% boys, 20% of JRA
Symptoms?
Usu. asymptomatic w/ recurrent AC inflammation
JIA Rx and Px
Treatment:
Steroids, immunomodulation
Avoid IOL after cataract surgery!
Worse prognosis if?
RF-, ANA+
Pauciarticular > Polyarticular
Lower limb joints > upper limb
Blau Syndrome
Familial juvenile systemic granulomatosis
Inheritance: AD
Multifocal choroiditis, vasculitic skin rash, polyarthritis, no pulmonary involvement
DDx of iritis + high IOP?
Fuchs Heterochromic Posner-Schlossman Sarcoidosis Herpetic uveitis Toxoplasmosis Syphilis
Fuchs heterochromic iridocyclitis
Young, unilateral, chronic
Clinical findings?
Iris stromal atrophy (heterochromia)
Minimal cell / flare in AC +/- ant vit
Diffuse stellate KP
Amsler sign? Heme during paracentesis from fine angle vessels (not NV) no PAS Cataracts (cortical) Glaucoma Infectious cause? Rubella, CMV Associated with toxoplasmosis
Treatment?
No steroids
Behcet syndrome
Idiopathic occlusive vasculitis
Common in?
Young adults; M>F
Eastern Mediterranean to Japan
HLA-B5 subset B51
Triad?
Iritis with hypopyon
Oral aphthous ulcers
Genital ulcers
Other ocular findings?
Panuveitis, retinitis, vasculitis, optic neuritis
Patchy retinal whitening (like CWS, but parallel to NFL)
Maybe quiet with hypopyon
Usually bilateral
Other systemic lesions?
Erythema nodosum, arthritis, epididymitis, GI ulcers, pulmonary artery aneurysms, CNS vasculitis + stroke
Treatment?
Immunosuppression (cyclosporine & azathioprine are proven in clinical trials)
Sarcoidosis
Black, age 20-50, M=F
Ocular involvement (50%)
Granulomatous ant. uveitis (most common)
Mutton-fat KPs
Iris nodules?
Koeppe (pupil margin; both granulomatous & non-granulomatous)
Busacca (iris stroma; only granulomatous)
Berlin (angle; only granulomatous)
Posterior uveitis Vitritis, vasculitis, CME, exudative RD Candle-wax dripping on retinal veins Choroidal granulomas Retinal lesions rare Optic nerve, poss. CNS involvement Eyelid skin nodules Lacrimal gland enlargement Conjunctival granulomas Band keratopathy Nummular keratitis
Systemic involvement
Hilar nodules
Gallium scan “Panda Sign”
Path?
Noncaseating granuloma
Langhans cell histiocytes
Mikulicz syndrome?
- Dry eyes from lacrimal, salivary gland involvement
Heerfordt syndrome?
- Constitutional symptoms, parotid swelling, facial nerve paralysis
Lofgren syndrome?
- Bilateral hilar lymphadenopathy, arthropathy, fever, erythema nodosum
Intermediate uveitis
Etiology? planitis Pars = Idiopathic (90%) Sarcoid, MS, Lyme, Toxocariasis, syphilis, TB, connective tissue dx 90% chronic/recurrent Usually bilateral
Clinical signs? Snowballs in vitreous Snowbanks on pars plana FA: peripheral venular cuffing + leakage Chronic changes: PAS, band keratopathy, CME, PSC, ERM, RD, vitreous cellular opacification, peripheral retinal NV, vitreous hemorrhage
Treatment?
Subtenon steroids, peripheral laser, IMT
Toxoplasmosis
Infection with T gondii (protozoan)
Acquired vs. Congenital?
Acquired: ingestion of bradyzoites from raw meat or cat litter)
Congenital: transmission of tachyzoites from mother’s blood
Ocular findings?
Vitritis/retinitis next to old scars (congenital lesions usually in macula; acquired lesions usually in periphery)
Headlight in fog appearance
Systemic signs in congenital toxo?
Seizures, cerebral calcifications
If AIDS patient, check neuroimaging (30% have brain lesions)
Toxoplasmosis Rx
Treatment? Triple therapy (x 1 yr if congenital) Pyrimethamine, sulfadiazine, folinic acid +/-prednisone Bactrim DS BID Atovaquone (attacks cyst too!) 750mg TID Clindamycin (if pregnant) Intravitreal clindamycin + dexamethasone
Presumed Ocular Histoplasmosis Syndrome Rx
Treatment? Steroids (PO or IVt) – no clear evidence Laser (based on MPS) for CNV Anti-VEGF for CNV Submacular surgery for CNV
Submacular Surgery Trial (SST): Modest benefit for CNV from POHS if BCVA <20/100
Presumed Ocular Histoplasmosis Syndrome Dx and demographic
Presumed infection with H. capsulatum (fungus)
Geographic associations?
Ohio-Mississippi River Valley
San Joaquin Valley
Typically age 20-50
HLA association? HLA-B7
Ocular findings? Punched-out chorioretinal scars (histo spots) Peripapillary atrophy CNV (5% of patients) No vitritis
Chest X-ray may show?
Hilar adenopathy or calcifications
DDx Posterior Uveitis - Infectious
o. Infectious: Bacterial endophthalmitis
o. Viral ARN CMV EBV Rubella Measles SSPE
o. Fungal
POHS (NO vitritis)
Candidiasis
o. Protozoal: Toxoplasmosis gondii
o. Helminthic
Toxocariasis canis
Cysticercosis
DUSN
Venules affected in posterior uveitis
Sarcoidosis
MS
Birdshot
Eales
Arterioles affected in posterior uveitis
Arterioles SLE PAN Toxo HSV/VZV
Immunologic Posterior Uveitis
o. Collagen vascular
SLE
PAN
Wegener granulomatosis
o. Retinochoroidopathies APMPPE ARPE/Krill (NO vitritis) Birdshot MEWDS PIC (NO vitritis) Serpiginous MCP
CMV retinitis Signs and path
Occurs when CD4
CMV Rx
Treatment?
Intravitreal ganciclovir or foscarnet
Induction x 2wks:
IV ganciclovir (5mg/kg BID; neutropenia)
IV foscarnet (90mg/kg BID; renal failure)
PO valganciclovir (900mg BID x 3wks)
Then lower dose & switch to PO: PO valganciclovir (900mg daily) Cidofovir (renal failure, uveitis, ciliary body shutdown; needs probenicid + IVF)
Common symptom of congenital CMV?
Hearing loss
Acute Retinal Necrosis (ARN)
Systemic condition?
Healthy NOT immunosupressed
Etiology? HSV, VZV, CMV Bilateral “BARN” (20%) Ocular findings? Occlusive retinal arteriolitis Severe vitritis Yellow-white peripheral retinitis Anterior uveitis RD (75%, highest risk at 8-12wks)
Treatment? Induction x 14 days: IV Acyclovir (800mg 5x/day) PO Famvir (500mg TID) PO Valacyclovir (1gm TID) Then lower dose, switch to PO Prophylactic laser for RD
Visual prognosis?
poor
Progressive Outer Retinal Necrosis
Systemic condition?
AIDS
Etiology?
VZV, other herpes viruses
Commonly bilateral w/ rapid progression
Ocular Findings?
Multifocal deep, dense retinal lesions
Mild vitritis
Spares retinal vasculature with cracked mud appearance (unlike ARN & CMV)
Treatment?
IV ganciclovir
Intravitreal foscarnet
DDx of Neuroretinitis?
Cat-Scratch disease DUSN Syphilis Lyme Leber idiopathic stellate neuroretinitis
Parinaud Oculoglandular Syndrome
Infection by?
Bartonella henselae (most common), tularemia, lymphogranuloma venereum, TB, syphilis, sporotrichosis, etc.
Usually occurs 2-3 weeks after scratch
Ocular findings? Unilateral Granulomatous conjunctivitis Preauricular adenopathy No leakage on FA
Treatment?
Supportive (disease self-limited)
Doxycycline +/- rifampin (if worse)
Other ocular manifestation of B.henselae?
Neuroretinitis
Disc edema, uveitis, macular star
Self-limited; spontaneous improvement
Diffuse Unilateral Subacute
Neuroretinitis (DUSN)
Helminth infection by? Toxocara canis Baylisascaris procyonis (N. America) Ancylostoma caninum (Southeast U.S.)
Ocular findings?
White dots in outer retina
with vitritis and papillitis
“Wiped-out” fundus late
Decreased ERG late
Treatment?
laser worm
Cysticercosis
Infection by?
Taenia solium tapeworm
Death of worm causes severe inflammation
West Nile Virus
Transmission by mosquito
Most infection subclinical (80%), or as febrile illness (20%)
Ocular findings present in 80% of cases with neurological involvement
Ocular findings?
Multifocal chorioretinitis with characteristic “target-like” lesions in mid-periphery
Randomly distributed or in linear arays
FA: early hypofluorescence and late staining
Non-granulomatous anterior uveitis
Conjunctivitis, subconjunctival hemorrhage
Optic neuritis
Treatment?
None; supportive therapy & infection control
Usually self-limited and symptomatic
DDx Multifocal CSCR
Hypotony Posterior scleritis Sympathetic ophthalmia VKH Lymphoma Lupus Uveal effusion syndrome
Lymphoma
Most common type?
Diffuse large B-cell lymphoma
Multiple deep yellowish spots, mild vitritis
FA finding?
Leopard skin fundus
Elevated intraocular levels of? IL-10 Especially in elderly Must rule out CNS lymphoma with LP Treatment: Whole-brain and ocular XRT Intrathecal MTX IV cytotoxic agents
VKH
Bilateral granulomatous panuveitis
Caused by autoimmunity to melanin/melanocytes
Asian, Native Americans, Hispanics, 30-50 y/o
Caucasians, Africans rare
Stages?
Treatment?
Periocular steroid injections
VKH Stage 1.
Stage 1. Prodromal:
Viral, CNS symptoms (HA, seizures, tinnitus)
VKH Stage 2.
Stage 2.Uveitis: Choroidal NV Optic neuropathy (disc edema) Hypotony Bilateral exudative RD, but CME rare
VKH Stage 3.
Stage 3. Convalescent:
Vitiligo, alopecia, poliosis
Sugiura sign (paralimbal vitiligo)
Sunset glow fundus (depigmented choroid)
VKH Stage 4.
Stage 4. Recurrent:
chronic uveitis
VKH Dx
CSF? Pleocytosis
U/S? Diffuse choroidal thickening
HLA? DR4
Path? Dalen Fuchs nodules. Also seen in SO.
Sympathetic Ophthalmia
Bilateral granulomatous panuveitis Entire uveal tract involved Antigen is uveal pigment Sparing of choriocapillaris SO has “sympathy” for the choriocapillaris, unlike VKH
Dalen-Fuchs nodules?
Collection of inflammatory cells on inner surface of Bruch’s membrane (between RPE and Bruch’s)
seen in VKH & SO
HLA-A29 assoc/w?
HLA-A29
Birdshot (96% strongest assocation)
HLA-B27 assoc/w?
Reiter’s, Ankylosing spondylitis, psoriatic arthritis, IBD
Whipple’s disease
JRA
Klebsiella (cross reaction)
HLA-B5 / B51 assoc/w?
Behcet’s disease
HLA-B7 assoc/w?
POHS
HLA-DR4 assoc/w?
VKH
HLA-DR15 assoc/w?
Pars planitis
Serpiginous/MCP/Birdshot have what in common?
Chronic Middle-Age Poor visual outcome Needs steroid therapy Associated with CNV
APMPEE/MEWDS/PIC have what in common?
Acute
Young
Good visual outcome
No treatment needed
Serpiginous/MCP/Birdshot differentiating factors?
M=F in serpiginous and birdshot
F> M in MCP
APMPEE/MEWDS/PIC differentiating factors?
F > M in MEWDS and PIC
M = F in APMPEE
Viral Prodrome/Mild Vitritis: MEWDS/APMPEE
Viral Prodrome/No Vitritis: PIC
Acute Posterior Multifocal Placoid Pigment Epitheliopathy (APMPPE)
Mnemonic: Acute Prodrome, Minor People, Prognosis Excellent
Occurs in young patients
1/3 have viral prodrome (days to weeks earlier)
Usually mild visual loss
Ocular findings?
Bilateral multiple creamy placoid subretinal lesions (FA: early hypo and late stain)
Mild vitritis
Systemic manifestations? Erythema nodosum Thyroiditis Microvascular nephropathy Cerebral vasculitis Etiology unknown, likely obstructive vasculitis with non-perfusion of terminal choroidal lobules
Treatment & Prognosis?
No treatment, good prognosis (80% has VA>20/40)
Self-limited, resolves in weeks to months
Serpiginous Choroiditis
Occurs in middle-age patients (age 30-60)
Similar to APMPPE, but chronic & recurrent
Usually asymptomatic until fovea affected
Ocular findings?
Bilateral grayish-yellow geographic lesion, usu. emanating from optic disc w/ snake-like appearance (FA: early hypo, late stain)
Mild vitritis
Risk of CNV if macula involved
Treatment & Prognosis?
Systemic steroids for active juxtafoveal lesions, IMT (e.g. azathioprine & cyclosporine) if recurrent
Anti-VEGF or laser if CNV occurs
Poor prognosis (50% has central VA loss)
Ampiginous Choroiditis
aka Relentless Placoid Choroidopathy
Ocular findings?
Bilateral multifocal lesions similar to APMPPE, but progresses relentlessly over months
Treatment & Prognosis?
Steroid & IMT (e.g MTX, Cellcept)
Multiple Evanescent White Dot Syndrome
Occurs often in young women (age 20-45)
1/3 have viral prodrome (days to weeks earlier)
Symptoms?
Blurred vision with shimmering photopsias
Enlarged blind spot
Ocular findings?
Unilateral white dots at level of RPE (FA: early hyper, wreath-like late stain)
Mild vitritis
Decreased A-wave on ERG
Treatment & Prognosis?
No treatment; good prognosis
Self-limited (self resolve in 3-10 weeks)
DDx enlarged blind spot?
Disc edema
ONH drusen
MEWDS
IEBSS
Punctate Inner Choroidopathy
Mainly in young myopic women (age 18-40)
Ocular findings?
Bilateral white-yellow chorioretinal lesions (~100-200 microns) mostly posterior pole (FA: early hyper, late stain)
No vitritis
Risk of CNV
Clinically similar to POHS, but symptomatic and negative Histoplasmin skin test
Treatment & Prognosis?
No treatment if no CNV
Good prognosis if no CNV (50-75% of patients have BCVA>20/25)
Birdshot Chorioretinopathy
Usually occurs in middle-age (age 40-60)
HLA Association?
HLA-A29 (highest association 95%, but also 7% of healthy)
Ocular findings?
Biilateral cream-colored spots (50-100mm) in posterior pole, usually radiating from optic nerve
FA findings?
subtle compared with ophthalmoscopic appearance
“quenching” (dye disappears quickly from vessels)
Mild vitritis; vascular attenuation & leakage
Optic disc edema or atrophy; CME
Painless eye
Decreased scotopic ERG
Monitoring?
CME & perivascular edema on OCT
HVF & ERG
Treatment & Prognosis?
Early aggressive IMT (cyclosporine, azathioprine, MTX, Cellcept)
Intravitreal triamcinolone
Poor prognosis chronic & recurring
