RYAN VOLUME 2 - White Spot Syndromes and Related Diseases #77 Flashcards
What are the White Spot Syndromes?
Group of diseases likely driven by autoimmune dysfuction and characterized by disruption of the outer retina, RPE and the choroid or a combination of these.
Shared characteristics: blurred vision, photopsias, visual field changes, floaters, changes in contrast sensitivity
Is there any evidence of autoimmunity?
Although there is not an anti-retina antibody, an increased prevalence of systemic autoimmunity exist in both patients with WSS and their first- and second-degrees relatives.
Birdshot Chorioretinopathy -
Definition
Multiple small, cream colored lesions scattered around the optic disc radiating to the equator in a shotgun pattern with histopathologic evidence that the primary lesion is in the choroid. Bilateral, chronic process with vitritis, retinal vasculitis and CME.
Strong link with HLA-A29.
Birdshot Chorioretinopathy -
Symptons
Blurred vision, floaters, photopsias.
Most have 20/40 or better.
Eye generally not red or painful.
Severe nyctalopia may occur.
VF and color vision changes may occur.
Birdshot Chorioretinopathy -
Epidemiology
6 - 7.9% with patients with posterior uveitis.
Slight female preponderance.
Mean reported age at the onset: 53 years.
White people / Northern European descent
HLA-A29 (present in 7% of white people).
>90% of patients with BCR are HLA-A29 positive.
Birdshot Chorioretinopathy -
How many subtypes are there for the HLA-A29
11 subtypes.
HLA-A2902 is most commonly associated with BCR.
HLA-A2902 us 20 times more prevalent in white people than the HLA-A29*01.
The rest subtypes are exceedingly rare.
Birdshot Chorioretinopathy -
Fundus findings
Oval/round lesions, 1/2 - 1/4 DD in size, deep retina/choroid.
Can be subtle and asymmetric. Can coalesce.
Tend to cluster close to the disc.
Linear radiation away from the disc.
Align with choroidal blood vessels.
RPE and overlying retina appear intact but in chronic stages there may be RPE atrophy.
Minimal AS inflammation.
Optic disc edema, retinal vasculitis, CME, ERM.
Retinal / CNV.
Birdshot Chorioretinopathy -
2006 consensus on BCR diagnosis
- Bilateral
- At least 3 peripapillary lesions inferior or nasal to the disc
- Low grade AS inflammation (< or = 1+ cells)
- Low grade vitreous inflammation (< or = 2+ vitreous haze)
Supportive findings
- HLA-A29 +
- Retinal vasculitis
- CME
Exclusion criteria
- Significant keratic precipitates
- Posterior synechiae
- Infectious, neoplasic or inflammatory disease that may cause choroidal lesions
Birdshot Chorioretinopathy -
Clinical course and prognosis
Chronic disease. Does NOT regress.
Symptoms may be present for years prior to the onset of fundus lesions.
VA may be good despite the symptoms.
VA may decrease slowly despite the treatment.
20/40 or better in the best eye in 75%.
CME in 50.5% - most common cause of vision loss.
CNV in 5% (near the disc and bilateral).
Optic disc edema leading to atrophy may occur.
Preservation of Arden ratio (EOG) may be a positive factor for better outcome.
Birdshot Chorioretinopathy -
Fluorescein angiography
Early hypofluorescence.
Late diffuse HYPERfluorescence.
Increased transit time, leakage with CME, optic disc hyperfluorescence, disc/retinal neovascularization
Vessel wall staining
Birdshot Chorioretinopathy -
Indocyanine Green Angiography
Hypofluorescent lesions during intermediate and late phases(active disease). Lesions appear to align with medium to large vessels.
Hypofluorescent lesions may occur prior to clinical lesions.
Choroidal vessels appear indistinct.
Chronic disease may appear as isofluorescent lesions.
ICGA may prove useful to monitor efficacy of treatment because lesions may disappear with treatment.
Birdshot Chorioretinopathy -
OCT
Thinning of the retina and choroid in periphery.
Discrete outer retinal and choroidal hypereflective foci.
Hyporeflective in the suprachoroidal space - correlates to the presence of symptoms.
Perivascular retinal thickness correlates to the activity of vasculitis.
Birdshot Chorioretinopathy -
OCT Angiography
Decreased vessel density (specially deep outer retinal plexus).
Decreased choroidal flow.
Larger choroidal vessels on the edges of the lesions.
Retinal capillary loops and ioncreased intercapillary spaces.
Thinning of the retina and hyperreflective foci in the outer retina.
Generalized thinning of the choroid and loss of Sattler’s layer.
Hyperreflective foci in the choroid.
Flow voids in the choroid.
— findings suggest that the the focal lesions develop in Haller’s layer eraly on and expand anteriorly if untreated.
Birdshot Chorioretinopathy -
Fundus autofluorescence
Hypoautofluorescent lesions. Usually, there are more hypoFAF lesions than clinical lesions
Diffuse hypoautofluorescence was correlated with chronicity.
Birdshot Chorioretinopathy -
Electroretinogram
Early stage disease abnormal ERG x Late stage disease abnormal ERG
Early - electronegative ERG pattern
- Supernormal ERG amplitudes
- Decrease in b-wave amplitude versus a-wave amplitude - inflammation
- Rod b-wave may be affected prior to the photopic b-wave and flicker
Late
- Progressive decrease in a-wave and b-wave amplitudes.
- 30 Hz flicker implicit time is abnormal in 70% of patients at baseline
ERG findings may improve with treatment.
Birdshot Chorioretinopathy -
Visual field
Peripheral constriction
Enlarged blind spot
Central / paracentral scotomas
Generalized diminished sensitivity
It is unlikely that the birdshots lesions themselves cause scotomas.
The changes may be reversible with immunosuppression - MONITORING component.
Birdshot Chorioretinopathy -
Adaptive optics
Patchy loss of photoreceptors on AO-SLO that colocalized with areas of photoreceptor disruption on OCT.
Reduced cone density.
Birdshot Chorioretinopathy -
Systemic associations
No definitive systemic associations.
Hearing loss / cutaneous vitiligo/ vascular disease.
Birdshot Chorioretinopathy -
Pathogenesis
Inflammation as a primary feature.
Lesions consist of an accumulation of lymphocytes (CD8+T that secret IL-17) in the choroid at multiple levels, occasionally associated with hemorrhage.
Nongranulomatous nodular choroidal infiltration was reported.
Increased IL-17 levels in the aqueous humor.
HLA-A29 - ERAP2 - IL-17
Birdshot Chorioretinopathy -
Diferential diagnosis
Sarcoidosis.
Sympathetic ophthalmia.
Pars planitis.
Syphilitic chorioretinitis.
Intraocular B-cell lymphoma.
MFC.
Panuveitis sd.
Birdshot Chorioretinopathy -
Management
Corticosteroids (oral, sub-tenon, intraocular)- reduce CME, inflammation and ON edema, improve symptoms.
Immunosuppressive therapy - consider when low dose steroids are not sufficient at controlling disease and for long-term refractory cases.
- Cyclosporine (inhibits T lymphocytes and prevents S-Ag-induced experimental uveitis). Nephrotoxicity / hypertension.
- Azathioprine / Mycophenolate mofetil / Methotrexate (antimetabolites) - bone marrow suppression and hepatotoxicity.
- Cyclophosphamide and chlorambucil (alkylating agents). bone marrow suppression / malignancies.
- Daclizumab (monoclonal antibody against alpha-subunit of the IL-2 receptor of T-cells)
-Infliximab / Adalimumab
- Secukinumab (Targeted IL-17 human monoclonal antibody) - was NOT found to be effective in early trials.
- Tocilizumab (IL-6 receptor antagonist) - beneficial in patients with refractory CME
Placoid Diseases
- Acute posterior multifocal placoid pigment epitheliopathy (APMPPE)
- Serpiginous choroiditis (SC)
- Relentless placoid chorioretinitis (RPC)
- Persistent placoid maculopathy (PPM)
Placoid lesions due to choroidal flow deficits
OCT: opacification of the Henle’s layer and variable loss in the ONL.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Symptoms
Onset of central vision loss, blurred vision, paracentral scotoma, metamorphopsia, “spots” in the vision and photopsias.
Bilateral 75%.
If unilateral, fellow eye involved in few days or weeks.
Headaches, stiff neck and malaise may accompany ocular symptoms.
Recent viral sd/ vaccination.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Epidemiology
Male = female
20 - 50 y.o.
Older individuals may have worse outcome with moderate or severe vision loss due to GA or CNV.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Fundus findings
Multiple round flat confluent cream-colored lesions with indistinct margins scattered in PP and periphery. Lesions of different ages can be visible.
The lesions tend to resolve centrally with hypopigmentation.
Later, mild pigment mottling and, finally, increasing coarse pigment clumping may ensue.
Lesions can enlarge.
Localized serous detachments may occur.
Vasculitis. Subhyaloid hemorrhage. CNV. Disc edema.
Variable uveitis.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Clinical course and prognosis
Improvement of the visual symptoms within 2 - 4 weeks.
60% of the eyes have residual visual symptoms.
Foveal involvemente - important prognostic marker
70% of the eyes present with foveal involvement.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Fluorescein angiography
Early hypofluorescence.
Late HYPERflourescence - staining (progressive/irregular)
As the process becomes inactive, HYPERfluorescence due to window defects in the mottled RPE develops
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Indocyanine Green Angiography
Early hypofluorescence. Late hypofluorescence.
As lesions heal, late hypofluorescence becomes smaller and less defined (supports choroidal ischemia).
More hypofluorescence in acute fase due to swollen outer retina and RPE.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
OCT
Serous detachment - bacillary detachment (splitting of the photoreceptor layer).
– presence of reflective material in the fluid
Mild hyperreflective area above the RPE in the photoreceptor layer corresponding to the placoid lesions.
Hyperreflective lesions radiating in the Henle fiber layer and widened choriocapillaris - acute phase
Drusen-like abnormalities and RPE disruption.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
OCT Angiography
Flow deficits. Improve as lesions heal.
Areas of deficits may extend beyond clinical lesions .
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Fundus autofluorescence
As lesions heal:
Clinically - lesions become pigmented centrally and have a halo of depigmentation
FAF - central intense HYPERautofluorescence and hypoautofluorescence corresponding to the depigmented halo.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Electrophisiology
ERG normal or minimally subnormal.
Abnormal Arden ration reported.
ERG and EOG may normalize
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Systemic associations
CNS - cerebral vasculitis / meningoencephalitis / stroke / sixth CN palsy / hearing loss.
– CSF: pleocytosis
MRI and CSF analysis are important!
Systemic vasculitis.
Erythema nodosum, ulcerative colitis, thyroiditis, nephritis, juvenile rheumatoid arthritis.
Granulomatosis with polyangiitis, pulmonary tuberculosis, sarcoidosis.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Pathogenesis
Vascular insult - choroidal ischemia - RPE and photoreceptor disruption.
Viral illness: mumps, adenovirus, coxsckievirus B.
Bacteria - Lyme, GAS.
Vaccine - influenza, varicella, menigoC conjugate, hep B.
Lymph T.
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Differential diagnosis
Acute syphilitic posterior placoid chorioretinopathy - FA, ICGA and OCTA do not show inner choroidal ischemia.
SC, RPC, PPM.
Systemic vasculitis
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) -
Management
Steroids - if CNS involvement.
Idiopathic Serpiginous Choroiditis
Helicoid peripapillary chorioretinal degeneration
Bilateral, chronic, progressive, assymetric
Outer retina, RPE, choriocapillaris and large choroidal vessels
Idiopathic Serpiginous Choroiditis
Clinical course
Asymptomatic until fovea affected,
Blurred vision. Paracentral scotomas (absolute in acute stage, relative when healing)
Idiopathic Serpiginous Choroiditis
Epidemiology
Healthy individuals
30 - 70 yo.
Slight male predilection.
Higher HLA-B7 - Finnish study.
Idiopathic Serpiginous Choroiditis
Fundus findings
Classic presentation
- One/several geographic patches of gray or creamy yellow placoid outer retinal and RPE lesions in the peripapilllary region.
- Progresses with recurrences in a centrifugal manner.
- Edematous outer retina
- Serous retinal detachmente.
- Lesions resolve with or without treatment in weeks.
- Extensive RPE and choriocapillaris atrophy.
- Recurrences at the edge of old scars but not always .
Macular serpiginous choroiditis
- Same, except for the location.
- Poorer prognosis.
- Misdiagnosed as AMD, macular dystrohpies or toxoplasmosis.
Idiopathic Serpiginous Choroiditis
Other ocular findings
Nongranulomatous anterior uveitis.
Fine vitreous cells.
CNV, vasculitis, ON edema, bilateral FTMH.
Idiopathic Serpiginous Choroiditis
Clinical course / prognosis
Recurrences with months / years intervals. Usually one eye is active at a time.
Healing in 2 - 8 weeks
Vision loss correlates to the foveal involvement
Idiopathic Serpiginous Choroiditis
Fluorescein angiography
Early phase hypofluorescence. Borders may be HYPER (intact choriocapillaris or leakage when old lesion).
Late phase HYPERfluorescence due to staining.
Idiopathic Serpiginous Choroiditis
Indocyanine green angiography
Early phase hypofluorescence.
Late phase hypofluorescence.
Better to assess the choroid / active lesions.
More extensive than FA and clinical evaluation.
Idiopathic Serpiginous Choroiditis
OCT
Retinal atrophy and disruption of photoreceptor layers.
RPE thinning, intraretinal fluid, cystic changes.
Choroid / deeper retinal layers increased reflectance.
Hyperreflective of ONL and Henle’s layer (OPL).
Idiopathic Serpiginous Choroiditis
OCT angiography
Decrease choriocapillaris flow.
Improves with treatment.
Idiopathic Serpiginous Choroiditis
Fundus autofluorescence
Active/inactive areas.
New lesions: HYPERautofluorescent.
Old lesions: hypoautofluorescent.
Recurrence: HYPERautofluorescence ant the border of older lesions.
Lag behind OCTA findings.
Idiopathic Serpiginous Choroiditis
Electrophisiology
ERG normal,
EOG abnormal if extense lesions.
Perimetry: scotomas may not be permanent.
Microperimetry may be able to detect subclinical lesions.
Systemic associations
Systemic lupus erythematosus, Crohn’s disease, celiac disease, extrapyramidal dystonia
Idiopathic Serpiginous Choroiditis
Pathogenesis
Unknown.
Inner choroid ischemia.
Lymphocytic infiltrate.
Virus (herpes family) / Candida.
Elevated factor VIII - occlusive mechanism
Degenerative etiology
Idiopathic Serpiginous Choroiditis
Diferential diagnosis
Tuberculosis related SC.
APMPPE.
WSS in general.
Sarcoidosis, systemic non-Hodgkin lymphoma, AAS, toxo, syphilis, posterior scleritis.
Lupus, toxemia of pregnancy, DIVC, thrombotic thrombocytopenic purpura, malignat hypertension
Idiopathic Serpiginous Choroiditis
Management
TB skin test, chest radiography, quantiferonTB gold
ACE, VDRL. FTA Abs, toxoplasma, viral screen.
AC tap if cells.
Steroids - agressive if foveal involvement.
When tapered, lesions may recur.
Immunosuppresive agents - same as BSC.
Tuberculous Serpiginous Choroiditis
More vitritis.
More multifocal lesions involvind the periphery.
Smaller lesions.
Similar FA.
FAF may distinguish
– Stippled autofluorescence of tuberculous disease
Choroidal infiltration and RPE elevation may be visible (OCT).
Francisella tularensis and Bartonella hanselae are also associated to SC
Relentless Placoid Chorioretinitis
Clinical symptoms
Epidemiology
Sudden painless vision loss.
Metamorphopsia and floaters.
17 - 51 yo.
Male = female
Relentless Placoid Chorioretinitis
Fundus findings
Bilateral posterior creamy-white lesions at the level of the RPE.
Lesions smaller than APMPPE.
As they heal, pigmented chorioretinal atrohpy develops.
Lesions can persist, grow and recur.
Hallmark: presence of numerous (>50 to hundreds) lesions with involvement anterior and posterior to the equator (periphery first, posterior pole later).
Mild vitritis.
SRF.
Disc swelling.
Iritis with KP’s.
Relentless Placoid Chorioretinitis
Clinical course
Prolonged.
Multiple relapses and recurrences (both eyes simultaneously)
Pigemented chorioretinal atrophy in weeks.
Central vision affected in untreated cases.Relentless Placoid Chorioretinitis
Relentless Placoid Chorioretinitis
Fluorescein angiography
Early hypofluorescence.
Late HYPERfluorescence (staining).
Relentless Placoid Chorioretinitis
ICGA
Early hypo.
Late hypo.
Relentless Placoid Chorioretinitis
OCT
SRF.
PED.
Central (zone 1): dome-shaped elevation in IS/OS junction. Loss of ellipsoid zone and RPE thinning with SRF.
Peripheral to this (zone 2): IS/OS thickened and SRF.
Outermost region (zone 3): normal IS/OS band and mild hyperreflective outer retinal layers.
Relentless Placoid Chorioretinitis
Fundus autofluorescence
Marked hypoautofluorescence in areas of widespread chorioretinal atrophy.
Zone 1: hypoauto
Zone 2: HYPERauto
Zone 3: hypoauto but less than in zone 1
Relentless Placoid Chorioretinitis
Electrophisiology
EOG and ERG may be reduced.
Relentless Placoid Chorioretinitis
Systemic associations
Hashimoto thyroiditis / aseptic meningitis
Relentless Placoid Chorioretinitis
Pathogenesis
Choroidal ischemia. Similar to APMPPE/ SC
Relentless Placoid Chorioretinitis
Diferential diagnosis
APMPPE and SC…
Relentless Placoid Chorioretinitis
Management
Steroids +/- immunosuppression
Adalimumab may be beneficial
Compare APMPPE, SC and RPC - photo on the phone
Persistent Placoid Maculopathy
Clinical Symptoms
Gradual decreased vision
No pain
More commonly in one eye
Photopsias and decline in color vision can occur
Persistent Placoid Maculopathy
Epidemiology
50 - 68 yo
Vision preserved until atrophy of RPE or CNV (both common)
Scarring occurs in the region of CNV
Persistent Placoid Maculopathy
Fundus findings
Bilateral, almost symmetric large whitish plaque-like lesions at the level of the outer retina and RPE.
Centered in the fovea.
Not contiguous to the optic disc.
Jigsaw pattern to the margins.
Gradual fading of the whitish lesions occurs (months - years).
Satellite lesions can occur.
RPE clumping and mottling can occur.
CNV is common.
No cells in the AS.
Vitreous cells may be present.
Persistent Placoid Maculopathy
Fluorescein angiography
Early hypofluorescence
Late HYPERfluorescence
Persistent Placoid Maculopathy
ICGA
Persistent hypofluorescence
Persistent Placoid Maculopathy
OCT
Hyperreflectivity of the ONL
Disruption of the ELM
Complete restoration of the outer retina could occur
Persistent Placoid Maculopathy
OCTA
Decreased flow of the choriocapillaris corresponding to the ICGA hypofluorescence
Apparently, the flux is impaired in the choriocapillaris only.
Persistent Placoid Maculopathy
Fundus autofluorescence
Hypoautofluorescence correlating with RPE damage
Healed lesions show hyperauto and hypoauto
Persistent Placoid Maculopathy
Eletrophysiology
Normal
Persistent Placoid Maculopathy
Systemic associations
Nothing definitive.
Hypertension is common
Persistent Placoid Maculopathy
Pathogenesis
Choriocapillaris hypoperfusion
Persistent Placoid Maculopathy
Differential diagnosis
SC, APMPPE, RPC, Syphilitic posterior placoid chorioretinitis.
Persistent Placoid Maculopathy
Treatment
Oral / periocular corticosteroids
Multifocal choroiditis / Punctate inner choroidopathy
Symptoms
Decreased central vision, photopsias, floaters, metamorphopsia, paracentral/temporal scotomas, ocular discomfort, photophobia (peripapillary lesions - activity of the disease).
More than half have 20/100 or less in the worse eye.
Multifocal choroiditis / Punctate inner choroidopathy
Epidemiology
White women with myopia (mean -4.6 D)
Second to sixth decades of life (most around 30s)
Multifocal choroiditis / Punctate inner choroidopathy
Findings
Acute phase: round/oval yellow lesions (1 to several hundred) in the outer retina and RPE. Size 50 to 1000 micra.
Posterior pole, peripapillary region and midperiphery.
Nasal retina often shows clustering.
When limited to the posterior pole, an occasional linear pattern forms.
Initial lesions: sub-RPE, neurosensory detachment may appear.
Lesions erupt into the overlying retina.
With time, the lesions evolve into chorioretinal scars.
After 2-3 years, they become more distinct and pigmented, similar to the punched-out lesions of POHS.
CNV is common. (25 - 30%).
If peripheral linear scars parallel to the ora: Schlaegel lines.
ON edema and atrophy may apper.
Peripapillary subretinal fibrosis: napkin ring.
Quiescent or mild to moderate anterior uveitis.
Non-granulomatous KP and posterior synechiae can be present.
Mild to moderate vitritis.
Findings may be asymmetric.
Multifocal choroiditis / Punctate inner choroidopathy
Fluorescein angiography
Early hypo
Late HYPER (stain)
Healed lesions: window defect
Dumbbell-shapped pattern of subretinal fibrosis
Multifocal choroiditis / Punctate inner choroidopathy
ICGA
Hypo (early/mid/late) round spots (more than FA and fundus exam)
Large choroidal vessels may cross the lesion areas
HYPERfluorescence of the wall of choroidal vessels was noted (possible vasculitis)
Multifocal choroiditis / Punctate inner choroidopathy
OCT
Nodular collections below the RPE that erupted into the subretinal space and outer retina (drusen like material).
Choroidal hyperreflectivity below the infiltrates.
Stages (Zhang)
Choroidal infiltrates - sub-RPE nodules - chorioretinal nodules - regression - retina herniation
Foveal outer retinal hyperreflectivity (FORH): hyperreflectivity finger-like projections extending from the RPE into the ONL associated with discontinuous interdigitation and EZ and extensions of the hyperreflective foci to the internal limiting membrane.
Multifocal choroiditis / Punctate inner choroidopathy
Fundus Autofluorescence
Hypoautofluor exceeding those that were clinically detected.
Many resolved with immunosuppression
HYPERauto borders or entire lesions can appear in active lesions
Multifocal choroiditis / Punctate inner choroidopathy
Electrophysiology
Cone and rod depression in MFC with retinal and choroidal atrophy.
Multifocal choroiditis / Punctate inner choroidopathy
VF
Blind spot enlargement (if normal optic nerve - Acute Idiopatic Blind Spot Enlargement [AIBSE] - MEWDS and MFC)
Peripapillary disfunction rather than optic nerve problem.
Scotomas in areas of PR loss, scarring or serous detachment.
Import to monitor the disease.
Multifocal choroiditis / Punctate inner choroidopathy
Systemic associations
EBV - not proven
– IgM against viral capsid antigen or the Epstein-Barr early antigen were present in patients with MFC.
Sarcoidosis
