White dot

syndromes
 Introduction

• Definition: Inflammatory disorders of Unknown cause that involve the outer

retina, retinal pigment epithelium ,or choroid ,or a combination, in one or
both eyes in their second to sixth decades of life.

• Associated with a viral prodrome but well defined etiology is lacking for
these conditions.

• Typically seen in young, otherwise healthy adults.

• Symptoms include photopsia, floaters, decreased night vision, blurred vision

and visual field loss.
 TYPES

• Bird shot Choroidoretinopathy(BCR)

• Multifocal choroiditis and panuveitis(MCP)
• Punctate inner choroidopathy (PIC)
• Subretinal fibrosis and uveitis syndrome(SFU)
• Multiple evanesecent white dot syndrome (MEWDS)
• Acute posterior multifocal placoid pigment epitheliopahty(APMPPE)
• Serpiginous choroidopathy
Laboratory evaluation:
• Serologic testing for syphilis is recommended in all patient.
• Screening for tuberculosis should be conducted in those patient with known
exposure or risks
• Ocular diagnostic tests include FFA, OCT, ICG angiography, ERG studies

Treatment:
• Many white dot syndrome are benign and self limited.
• A few white dot syndrome are persistent and progressive with significant visual
consequences if untreated like MCP, Serpiginous choroiditis and birdshot
choroidopathy
• Mainstay of treatment includes local or systemic corticosteroids
 DIFFERENTIAL DIAGNOSIS

INFECTIOUS D/D NON INFECTIOUS D/D

• SYPHILIS • SARCOIDOSIS
• PRIMARY OCULAR HISTOPLASMOSIS • VKH SYNDROME
SYNDROME • SYMPATHETIC OPHTHALMIA
• TUBERCULOSIS • INTRAOCULAR LYMPHOMA
• DIFFUSE UNILATERAL SUBACUTE NEURO
RETINITIS.
Bird shot Choroidoretinopathy
• It is a bilateral and chronic process affecting choroid.
• Females are affected more then men within age group 40s-60s.
• HLA-A29 mutation is strongly associated with bird shot retinopathy.(seen in 95%
of patient)
• Symptoms - blurred vision, floaters, photopsia, defective colour vision and severe
nyctalopia despite normal visual acuity may also be a presenting symptom.
• Fundus –Multiple ill defined small, cream-colored, choroidal patches less than
one disc diameter in size, scattered around the optic disc and radiate to the
equator in a “shotgun” pattern involving posterior pole and midperiphery retina.

• The lesions radiate outward from the disc but spare the macula.

• They may appear to follow choroidal blood vessels peripherally.

• Other findings – Vitritis is a prominent finding along with retinal vasculitis
and optic disc edema.
• CME (in about 50% of patients) and epiretinal membrane (ERM)
formation may also develop.

• Diffuse narrowing of the retinal arterioles, perivascular nerve fibre layer

haemorrhages, and tortuosity of retinal vessels are seen. Choroidal
neovascularization (CNV) can occur.

• Histopathology- These suggest that the spots may be related to accumulation of

lymphocytes in the choroid at multiple levels, occasionally associated with
hemorrhage.
• FFA - The lesions shows hypofluorescence in the early phase, and diffuse
hyperfluorescence in the late phases.

• ICGA- the birdshot lesions appear hypofluorescent during the intermediate phase
of angiography and appear to be bordered by medium-to-large vessels.

• OCT - shows significant thinning of the retina and choroid in the peripheral
locations. Macular edema is confirmed with OCT.
• ERG- normal, but with time show rod and cones abnormalities.
Rx-

Corticosteroids have been the mainstay of treatment. Oral, sub-Tenon, intraocular

inj may be given and most recently sustained release fluocinolone acetonide have
been used.
• Immunosuppressives like – cyclosporine, azathioprine, methotrexate have been
used as monotherapy or as an adjunctive.

• Anti- VEGF’s therapy for choroidal neovascularization and CME patients can be
given.
 Multifocal choroiditis and
•panuveitis
Multifocal choroiditis and panuveitis (MCP) is an idiopathic inflammatory disorder
of unknown etiology affecting the choroid & retina.
• It is most often seen in myopic women between second and sixth decade of life
presenting with photopsia, decreased vision, floaters, photophobia.
• Usually bilateral but may be asymmetric with delayed development in fellow
eye.
• The etiology is not known but may be due to sensitization of antigens within
photoreceptors & retinal pigment epithelial cells by an exogenous pathogen. (
Epstain barr virus or HSV )
• Signs- anterior uveitis in 50% cases, vitritis, multifocal choroiditis.

• Fundus- Multiple discrete, ovoid, yellowish grey lesions 50-350 micrometer in

diameter at the posterior pole and periphery, sometimes with linear clusters or
streak pattern.(D/D- POHS)

• Inactive lesions have sharply defined margins and pigmented borders.

• Peripapillary atrophy and optic disc edema may be present.

• It is associated with CME, deep choroidal neovascular membrane, ERM

formation. Diffuse subretinal fibrosis can also develop.
• FFA - FA in the acute stage show early hypofluorescence & late
hyperfluorescence.

• ICGA- shows hypofluorescent lesions suggestive of active choroiditis

commonly clustered around disc.
• ERG- normal until advanced retinal atrophy.
• VISUAL FIELD- large defects are seen not corresponding with examination
findings are seen.

Rx-
• Topical or systemic steroids. In chronic cases immunosuppressive agents can
be considered.
• Choroidal Neovascularisation can be managed with anti-VEGF therapy
with or without the use of corticosteroids.
Late staining on FFA
Punctate inner
choroidopathy
• It is an idiopathic inflammatory disease of the choroid.
• Young myopic females are affected with bilateral involvement.
• Association with Epstein-Barr virus and with HLA-DR2 positivity has been
reported.
• Symptoms – blurring of vision, floaters, photopsia or paracentral scotomas.
• Signs- anterior uveitis or vitritis is mild or may be absent.
• Cells and flare in the anterior chamber or vitreous cavity are typically absent.
The lack of vitreous inflammation is a hallmark of PIC.

• Fundus- several small yellow-white macular spots with fuzzy borders at the
level of the inner choroid and retina which may evolve into sharply demarcated
atrophic scars with little pigmentation.
• Serous retinal detachment may occur overlying an active lesion.

• Choroidal neovascular membranes occur in between 40 to 75% of patients from

healed scars. Recurrences are common.

• FA – Early hyperfluorescence and late staining of lesions.

• ICG shows numerous hypofluorescent spots in the middle and late phases

Rx-
• Systemic Corticosteroids are used in the active stages. CNV can be managed
with anti-VEGF injections in combination with oral steriods.
(C) FA arterial phase (D) FA late phase of eye
Sub-Retinal Fibrosis and Uveitis
Syndrome
• It is a rare form of panuveitis of unknown etiology affecting otherwise
healthy myopic women between the ages of 14 and 34 years.
• Autoimmune etiology has been implicated with the demonstration of local
antibodies and B-lymphocytes.

• Symptoms – It presents with unilateral symptoms despite bilateral

involvement detected on clinical examination.
• Signs- mild to moderate vitritis and anterior uveitis are seen.

• Fundus- white yellow lesions (50-500 μm) located in

the posterior pole to midperiphery at the level of the RPE.
• these lesions are accompanied by the appearance of turbid subretinal exudation
& this differentiates SFU from other white dot syndrome
• Over the next several months to years, the subretinal fibrin and turbid exudates
coalesce into large, white, stellate zones of subretinal fibrosis to involve most of
the retina and choroid.
• Serous neurosensory retinal detachment, CME, and CNV may also be observed.

• FFA- the acute lesions show early hyperfluorescence followed by late leakage.

• The disease course is marked by chronic recurrent inflammation and the visual
prognosis is guarded.

• Treatment is directed towards early diagnosis and aggressive management to

prevent fibrosis setting in the other eye.

• Once severe subretinal fibrosis develops, treatment has little benefit

Multiple evanescent white dot
syndrome
• It is an idiopathic inflammatory disorder of retina.
• It usually affects otherwise healthy, young, moderately myopic females in their
second to fourth decades of life.
• Symptoms- Patient presents with acute, painless, unilateral blurred or decreased
vision, photopsias, and central or paracentral scotoma corresponding to an
enlarged physiologic blind spot.
• Signs- mild vitritis may be present with disc edema.

• Fundus- multiple small (100-200 micron), ill-defined, grey white spots sparing the
fovea (perifoveal) at the level of the RPE or deep retina. These spots fade away
and are frequently missed but leave behind a characteristics orange granular
macular pigmentary change which is pathognomic and a dulled reflex.
• Rarely CNV may develop and may be the presenting sign.

• FFA- it may reveal disc capillary leakage and late punctate staining,
characteristically in a wreath like pattern.

• ICGA- multiple hypofluorescent spots that are more numerous than those
seen clinically or in FA.

• Visual field defects are variable and range from generalized depression,
paracentral or temporal scotoma to enlargement of the blind spot.
( D/D- Retrobulbar optic neuritis)

• ERG- profound decrease in a-wave amplitude.(increase in b/a ratio).

• Prognosis is excellent with visual recovery in 2-10 weeks without

treatment.
However, residual symptoms including photopsias and enlargement of the blind
spot may persist for months.

• Recurrences are uncommon (10-15 % of patients) and have a similarly good

prognosis.

• Treatment is not needed in view of the favourable natural course.

Acute posterior multiocal placoid
pigment epitheliopathy(APMPPE)
• It affects healthy young adults with no gender predilection.
• It is an acute condition which starts unilaterally and then becomes bilateral.
• An antecedent viral prodrome occurs, and it is speculated to occur because of cell
mediated immunity to viral antigen.(mumps, adenovirus, coxsackivirus) .
• Associated with erythema nodosum, Wegener granulomatosis, polyarteritis
nodosa, cerebral vasculitis, scleritis and episcleritis, sarcoidosis and
ulcerative colitis indicating towards auto immune pathology.
• A genetic predisposition may be present as there is association of HLA-B7
and HLA-DR2.
• Symptoms – sudden onset of unilateral diminution of vision , photopsia, fellow
eye is affected within few days or weeks, headache and other neurological
symptoms are common

• Signs – Anterior segment is quiet with mild vitritis.

• Fundus- multiple, large, flat, yellow creamy to placoid lesions at RPE level.
They are 1-2 disc diameters in size and are located throughout the posterior
pole.

• Acute lesions heal over a period of 2-6 weeks with RPE pigmentary alterations &
resultant chorioretinal atrophy.

• Atypical findings include papillitis, retinal vasculitis, retinal vascular occlusive

disease, retinal neovascularization, and exudative retinal detachment.
• FFA –early hypofluorescence with late hyperfluorescent staining.
• ICGA – demonstrates non perfusion of choriocapillaries or focal
hypofluorescence is seen.
• Lumbar puncture and CNS imaging to be done in patients with neurological
symptoms.

Rx-
• APMPPE is a self limiting condition which needs no treatment.
• Recurrences are less
• There are no convincing data to suggest that treatment with systemic
corticosteroids is beneficial in altering the visual outcome.
• It may be used in patients with extensive macular involvement, CNS,
vasculitis & other associated autoimmune conditions
Serpiginous
choroidopathy
• It is also known as geographical helicoid peripapillary choroidopathy (GHPC).
• It affects healthy patients from the second to seventh decades of life. Men and
women are affected equally.
• It is usually bilateral but highly assymetrical, chronic, and progressive
inflammatory condition.
• Its etiology is unknown.
• Associated with HLA- B7 and retinal s-antigen.
• The disease is usually recurrent over years with relatively poor prognosis.
• Symptoms – patient present with painless, unilateral, paracentral scotomata
and decreased vision.
• Signs – mild vitritis.
• Fundus shows asymmetric bilateral disease with characteristic gray white
lesions at the level of the RPE with a pseudopodial or geographic extension
from the peripapillary area into the posterior fundus.

• The disease starts around optic disc and extends gradually. Around 5% cases have
the disease starting at central macula

• The healed inactive chorioretinal lesions appear as well-demarcated geographic

atrophic areas with or without pigment epithelial hyperplasia.

• Recurrent attacks are typical with a progressive centrifugal extension

• Late complications include retinal vein occlusion, macular hole, subretinal fibrosis
and CNV usually occurring at the border of an old scar.
• FFA- shows early hypofluorescence and then late staining of the active edge of
the lesion

• ICGA- hypofluorescence throughout all phases of the study for both acute and old
lesions

• Other investigations - investigated for TB, syphilis, sarcoidosis,

Rx- systemic steroids.

• immunosuppressive (cyclosporine, azathioprine,cyclophosphamide) may

be effective alone or in combination,
Reference
s
• Ryan’s retina edition 6 – section 4 chapter 79
• White dot syndromes - Delhi J Ophthalmol 2015; 25 (4): 223-232