Ophthalmology – Multifocal Choroiditis / Punctate Inner Choroiditis

Basics

Description

Multifocal choroiditis (MFC) and punctate inner choroiditis (PIC) are inflammatory disorders affecting the choroid and outer retina.

Multifocal choroiditis with panuveitis is characterized by:

• Multiple active choroidal or chorioretinal lesions
• Vitreitis
• Frequently anterior uveitis
• Recurrent episodes of intraocular inflammation
• Risk of choroidal neovascularization and permanent chorioretinal scarring

Punctate inner choroiditis is closely related but typically:

• Occurs in young myopic women
• Produces small inflammatory lesions predominantly in the posterior pole
• Has little or no anterior chamber inflammation or vitreitis
• Frequently causes photopsias and central/paracentral scotomas

A related severe phenotype is diffuse subretinal fibrosis (DSF), in which inflammatory lesions coalesce and produce extensive subretinal fibrosis.

Etiology

The exact cause of MFC and PIC remains unknown.

They are believed to represent immune-mediated inflammatory chorioretinal disorders.

Possible mechanisms include:

• Abnormal autoimmune response against ocular antigens
• Molecular mimicry after exposure to an infectious or viral antigen
• Genetic susceptibility combined with an environmental trigger

MFC, PIC, and diffuse subretinal fibrosis may represent different manifestations along a common inflammatory disease spectrum.

Epidemiology

Multifocal Choroiditis

Typically affects:

• Young to middle-aged adults
• Women more often than men
• Commonly patients in the third to fourth decades of life

Punctate Inner Choroiditis

Classically occurs in:

• Young women
• Frequently myopic patients
• Otherwise healthy individuals

Both disorders may be bilateral, although disease activity may be markedly asymmetric.

History

Patients with MFC are usually otherwise healthy.

Some report a preceding:

• Viral-like illness
• Upper respiratory infection
• Nonspecific systemic prodrome

Common ocular complaints include:

• Blurred or decreased vision
• Floaters
• Photopsias
• Scotomas
• Peripheral visual field loss
• Metamorphopsia
• Distorted central vision

Symptoms may develop gradually.

Although patients may notice symptoms in only one eye initially, bilateral involvement is common.

Punctate Inner Choroiditis Symptoms

Patients with PIC commonly report:

• Photopsias
• Central or paracentral scotomas
• Metamorphopsia
• Blurred central vision

Because PIC often lacks significant anterior chamber or vitreous inflammation, the eye may appear externally quiet.

Physical Examination

Multifocal Choroiditis

Typical examination findings include:

• Vitreitis in most patients
• Anterior chamber inflammation in approximately half of cases
• Multiple yellow-white choroidal or chorioretinal lesions
• Pigmented borders around older lesions
• Chorioretinal scars in healed disease

The lesions:

• Are usually approximately 50–300 μm
• May occur throughout the posterior pole and peripheral fundus
• Represent focal inflammatory involvement of the choroid and outer retina

Older lesions often become:

• Punched-out
• Atrophic
• Pigmented

Punctate Inner Choroiditis

PIC lesions are generally:

• Small
• Yellow-white
• Located at the posterior pole
• Often at the level of the inner choroid/RPE/outer retina

Unlike classic MFC:

• Vitreitis is typically absent or minimal
• Anterior uveitis is generally absent

This distinction is clinically useful.

Diffuse Subretinal Fibrosis

In severe disease, multiple inflammatory lesions may coalesce, producing:

• Broad zones of subretinal fibrosis
• Macular distortion
• Extensive photoreceptor and RPE damage
• Severe irreversible visual loss

This phenotype is referred to as diffuse subretinal fibrosis syndrome.

Diagnostic Tests & Interpretation

Laboratory Evaluation

There is no specific laboratory test that confirms MFC or PIC.

Testing is primarily directed at excluding infectious and systemic inflammatory mimickers.

Depending on history, examination, and geographic exposure, investigations may include:

• Syphilis serology
• Tuberculosis testing
• Sarcoidosis evaluation
• Toxoplasmosis testing
• Lyme disease testing when epidemiologically appropriate

Before initiating systemic immunosuppression, baseline investigations commonly include:

• Complete blood count
• Liver function tests
• Renal function tests
• Screening for latent infection according to the proposed immunomodulatory agent

Imaging

Fundus Photography

Color and red-free fundus photography are useful for:

• Baseline documentation
• Assessing lesion distribution
• Comparing active versus healed lesions
• Monitoring progression or recurrence
• Documenting scar formation

Fluorescein Angiography

Fluorescein angiography (FA) is useful for identifying:

• Clinically inapparent lesions
• Active inflammatory lesions
• Choroidal neovascularization
• Cystoid macular edema
• Vascular leakage

Active lesions

Typically demonstrate:

• Early hypofluorescence from blockage
• Progressive hyperfluorescence or staining in later phases

Inactive lesions

May demonstrate:

• Window defects from RPE atrophy
• Late staining
• Persistent hypofluorescence if choriocapillaris loss is severe

Optical Coherence Tomography

OCT is essential for evaluating the macula.

It can demonstrate:

• Disruption of the outer retinal layers
• Photoreceptor loss
• RPE changes
• Subretinal fluid
• Intraretinal fluid
• Cystoid macular edema
• Choroidal neovascular membrane
• Fibrotic scar formation

Serial OCT is extremely useful for monitoring:

• Disease activity
• Treatment response
• Development of CNV
• Resolution of macular edema

OCT in PIC

Modern spectral-domain OCT may demonstrate focal abnormalities involving:

• RPE
• Ellipsoid zone
• Outer nuclear layer
• Choroid

Active lesions may protrude through or disrupt the RPE and outer retina before evolving into atrophic scars.

Indocyanine Green Angiography

Indocyanine green angiography may demonstrate more extensive choroidal involvement than is clinically visible.

It can show:

• Multiple hypofluorescent choroidal spots
• Areas of occult inflammatory activity

It may be particularly useful when the clinical diagnosis is uncertain.

Fundus Autofluorescence

Fundus autofluorescence can assist in demonstrating:

• Active RPE stress
• Areas of RPE loss
• Subclinical lesions
• Progression of chorioretinal atrophy

Hyperautofluorescent borders may indicate active or stressed RPE, whereas established atrophy generally becomes hypoautofluorescent.

Visual Field Testing

Visual field testing may show:

• Paracentral scotomas
• Peripheral field defects
• Enlarged blind spot

Visual field defects do not always correspond directly to currently active choroidal lesions.

Follow-Up During Active Disease

During active inflammation, patients may require examination every:

1–4 weeks

depending on:

• Severity
• Macular involvement
• Degree of vitreous inflammation
• Presence of CNV
• Treatment being used

Choroidal Neovascularization

One of the most important complications of both MFC and PIC is:

Choroidal neovascularization (CNV)

It may develop:

• Beneath the macula
• Adjacent to active inflammatory lesions
• In old scars
• In the peripapillary region
• Even after active inflammation has subsided

Patients should be educated to recognize:

• New metamorphopsia
• New central scotoma
• Sudden reduction in central vision

Amsler Grid

Home Amsler grid monitoring may help identify:

• New distortion
• New central scotoma
• Blurring
• Possible development of CNV

Any new change warrants prompt examination.

Differential Diagnosis

Important differential diagnoses include:

• Ocular syphilis
• Tuberculosis
• Toxoplasmosis
• Presumed ocular histoplasmosis syndrome
• Sarcoidosis
• Central serous chorioretinopathy
• Age-related macular degeneration
• Choroidal neovascularization from other causes
• Ocular trauma
• Acute posterior multifocal placoid pigment epitheliopathy
• Multiple evanescent white dot syndrome
• Birdshot chorioretinopathy
• Vogt–Koyanagi–Harada disease
• Intraocular lymphoma in atypical cases

Treatment

Treatment is determined by:

• Degree of active inflammation
• Laterality
• Macular involvement
• Presence of CNV
• Recurrence frequency
• Degree of structural damage

Medication

First Line

For significant posterior inflammation, topical corticosteroids alone are generally inadequate.

Treatment may include:

• Systemic corticosteroids
• Periocular corticosteroid injection
• Intravitreal corticosteroid therapy in selected cases

Topical corticosteroids may still be useful when there is significant anterior uveitis.

Important Precaution

Infectious causes must be excluded before starting corticosteroids or systemic immunosuppressive therapy.

Immunosuppression of an undiagnosed infectious posterior uveitis may result in severe disease progression.

Systemic Corticosteroids

Oral corticosteroids may be useful for:

• Bilateral disease
• Severe posterior inflammation
• Vision-threatening macular involvement
• Extensive active lesions

Long-term systemic corticosteroid therapy should generally be avoided when a steroid-sparing treatment strategy is appropriate.

Second-Line Therapy

Systemic immunomodulatory therapy may be indicated when:

• Disease is recurrent
• Inflammation is chronic
• Corticosteroid dependence develops
• Disease is bilateral and vision-threatening
• Corticosteroid toxicity is problematic

Potential steroid-sparing agents include, depending on the patient:

• Methotrexate
• Mycophenolate mofetil
• Azathioprine
• Cyclosporine
• Tacrolimus
• Selected biologic agents in refractory disease

These treatments require appropriate systemic monitoring.

Pregnancy Considerations

Many immunomodulatory drugs may:

• Be teratogenic
• Affect fetal development
• Require discontinuation before conception

Treatment in pregnancy should therefore be coordinated with:

• Uveitis specialist
• Obstetrician
• Rheumatologist or other prescribing specialist

Choroidal Neovascularization Treatment

Modern treatment for inflammatory CNV generally centers on:

Intravitreal anti-VEGF therapy

Examples include:

• Bevacizumab
• Ranibizumab
• Aflibercept

Treatment of underlying inflammatory activity may also be necessary.

Historically used treatments include:

• Photodynamic therapy
• Thermal laser photocoagulation in selected extrafoveal lesions

These are used much less commonly than anti-VEGF therapy for macular CNV.

Cystoid Macular Edema

CME may respond to:

• Periocular corticosteroid
• Intravitreal corticosteroid
• Systemic anti-inflammatory therapy

Anti-VEGF treatment may occasionally be used depending on the mechanism and associated pathology.

Issues for Referral

Because posterior uveitis has numerous infectious and inflammatory mimickers and can cause permanent vision loss, patients should generally be managed by or referred to a:

Uveitis specialist

Additional referral may be needed to:

• Retina specialist for CNV, macular edema, or structural complications
• Rheumatology for systemic immunomodulatory therapy
• Infectious disease when an infectious cause is suspected

Surgery / Other Procedures

Cataract Surgery

Chronic inflammation and corticosteroid treatment may cause cataract.

Cataract surgery can be considered when:

• Cataract is visually significant
• Inflammation has been well controlled
• The eye has been appropriately quiet before surgery

Perioperative anti-inflammatory therapy is often required.

Steroid Implants

Sustained-release intraocular corticosteroid implants may be considered in selected cases of:

• Chronic posterior uveitis
• Recurrent disease
• Inadequate response to other therapy

Potential complications include:

• Cataract
• Ocular hypertension
• Glaucoma

Vitrectomy

Pars plana vitrectomy may be considered for:

• Visually significant vitreous opacities
• Diagnostic uncertainty
• Suspected intraocular lymphoma or infection
• Selected structural complications

Diagnostic vitreous sampling may be particularly important in atypical presentations.

Ongoing Care

Long-term follow-up is important because disease may recur after prolonged periods of inactivity.

Monitoring should include:

• Visual acuity
• Slit-lamp examination
• Vitreous inflammation
• Dilated fundus examination
• OCT
• Assessment for CNV
• Intraocular pressure
• Cataract development

Patient Education

Patients should be advised to seek prompt review for:

• New photopsias
• New floaters
• New scotoma
• Metamorphopsia
• Sudden or progressive central visual loss

Home Amsler grid monitoring can be useful.

Prognosis

MFC and PIC often follow a chronic or relapsing course lasting months to years.

Visual prognosis depends primarily on:

• Macular involvement
• Recurrent inflammation
• Development of CNV
• Cystoid macular edema
• Photoreceptor loss
• Extent of chorioretinal scarring
• Diffuse subretinal fibrosis

Patients without foveal involvement may maintain good central vision.

Repeated macular inflammation, CNV, or extensive fibrosis can result in severe permanent visual impairment.

Complications

Important complications include:

• Choroidal neovascularization
• Cystoid macular edema
• Subretinal fibrosis
• Chorioretinal atrophy
• Photoreceptor loss
• Cataract
• Ocular hypertension
• Glaucoma
• Steroid-related complications
• Permanent central visual loss

CNV may occur even when there is no clinically active inflammation, making long-term surveillance essential.

Ophthalmology Pearls

• MFC = multifocal choroidal lesions + vitreitis ± anterior uveitis.
• PIC = young myopic women + posterior pole punctate lesions + little or no vitreitis.
• The two disorders likely belong to a related inflammatory spectrum.
• CNV is one of the most important causes of visual loss and may develop even after inflammation appears inactive.
• OCT is indispensable for distinguishing inflammatory damage from treatable complications such as CNV, CME, or subretinal fluid.
• Before immunosuppression, exclude important infectious mimickers—particularly syphilis and tuberculosis.
• Anti-VEGF therapy is the main contemporary treatment for inflammatory CNV.
• Recurrent disease can lead to extensive subretinal fibrosis and irreversible visual loss.
• Long-term, often lifelong ophthalmic surveillance is appropriate because recurrence and CNV can occur after apparently quiet intervals.