Ophthalmology – Presumed Ocular Histoplasmosis Syndrome

Basics

Description

Presumed ocular histoplasmosis syndrome (POHS) is a characteristic chorioretinal syndrome associated epidemiologically with prior exposure to Histoplasma capsulatum.

It is defined clinically by the classic combination of:

• Multiple punched-out chorioretinal scars (“histo spots”)
• Peripapillary chorioretinal atrophy
• Absence of anterior chamber inflammation and vitritis

The major sight-threatening complication is:

Macular neovascularization (MNV/CNV)

which may produce hemorrhage, exudation, subretinal fluid, fibrosis, and permanent central visual loss.

Important Modern Concept

The association between POHS and Histoplasma capsulatum is strong epidemiologically but remains:

Presumed rather than microbiologically proven in most affected eyes.

Classic POHS is not considered an active fungal infection of the eye.

Therefore:

• Antifungal therapy is not indicated for typical POHS
• Corticosteroids are not routine treatment
• Management is directed primarily toward MNV detection and treatment

Epidemiology

POHS is most strongly associated with areas where H. capsulatum is endemic, particularly in the United States:

• Ohio River Valley
• Mississippi River Valley
• Parts of the central and eastern United States

Many people in endemic regions have been exposed to Histoplasma without developing POHS.

Only a small proportion develop the characteristic ocular phenotype.

Histoplasma Exposure

Histoplasma capsulatum is a dimorphic fungus found particularly in soil contaminated by:

• Bird droppings
• Bat droppings

Exposure may occur around:

• Caves
• Chicken coops
• Old buildings
• Demolition sites
• Excavation
• Soil disruption

Most infections are:

• Asymptomatic
• Mild respiratory infections

The ocular syndrome may become clinically apparent long after the presumed systemic exposure.

Pathogenesis

The precise mechanism remains uncertain.

A proposed sequence is:

Prior systemic Histoplasma exposure → hematogenous seeding or immune-mediated choroidal injury → healed focal chorioretinal scars → later MNV in susceptible lesions

However, viable fungal organisms are generally not demonstrable in classic POHS lesions.

Thus the current concept favors:

• Prior infectious trigger
• Subsequent inflammatory/chorioretinal scarring
• Late neovascular complications

rather than chronic active fungal infection.

Genetics

Certain HLA associations have historically been reported, suggesting that:

Host immune susceptibility may influence the development of POHS

after Histoplasma exposure.

Routine genetic testing has no clinical role.

Clinical Presentation

Patients may be:

Completely asymptomatic

if lesions are peripheral or inactive.

Symptoms usually arise when MNV develops near the macula.

These may include:

• Metamorphopsia
• Central blur
• Paracentral scotoma
• Micropsia
• Reduced central vision

Laterality

POHS may be:

• Unilateral clinically
• Bilateral

Even when symptoms occur in only one eye, the fellow eye may show:

• Histo spots
• Peripapillary atrophy

Classic Fundus Triad

The classic triad is:

1. Punched-out chorioretinal scars
2. Peripapillary atrophy
3. No vitritis

The absence of vitreous inflammation is particularly important diagnostically.

Histo Spots

Histo spots are small, discrete, round or oval areas of:

• Chorioretinal atrophy
• RPE disturbance

They are commonly:

• Yellow-white when relatively fresh
• Pigmented or atrophic when healed

They may occur in:

• Macula
• Midperiphery
• Peripheral retina

Macular Histo Spots

Macular histo spots are clinically important because they increase the risk of:

Secondary MNV

which is the major cause of severe visual loss in POHS.

Peripapillary Atrophy

Typical peripapillary findings include:

• Circumferential or irregular chorioretinal atrophy
• Pigmentary alteration adjacent to the optic nerve

This may be subtle or extensive.

Histo Streaks

Linear chorioretinal scars may occasionally be seen and have historically been called:

Histo streaks

These are less diagnostically important than the classic triad.

Absence of Inflammation

Classic POHS lacks:

• Anterior chamber cells
• Vitreous cells
• Vitreous haze

This feature helps distinguish it from inflammatory disorders such as:

Multifocal choroiditis with panuveitis

Macular Neovascularization

MNV may develop adjacent to:

• Macular histo spots
• Peripapillary scars

Typical manifestations include:

• Gray-green subretinal lesion
• Subretinal hemorrhage
• Intraretinal or subretinal fluid
• Lipid exudation
• Pigment epithelial detachment
• Fibrosis

Peripapillary MNV

POHS may also produce:

Peripapillary MNV

which can enlarge toward:

• Papillomacular bundle
• Fovea

and become visually significant.

Disciform Scar

Untreated or chronic MNV may evolve into:

• Fibrovascular scar
• Disciform macular scar

causing permanent central vision loss.

Diagnosis

POHS is a:

Clinical diagnosis

There is no laboratory test that confirms classic ocular disease.

Diagnosis rests on:

• Characteristic fundus findings
• Lack of vitreous inflammation
• Compatible epidemiologic history
• Imaging when MNV is suspected

Laboratory Testing

Routine testing for:

• Histoplasma antibodies
• Serum antigen
• Urine antigen

is generally:

Not useful for isolated POHS

because these tests are designed primarily for diagnosing active systemic histoplasmosis.

Histoplasmin Skin Testing

Histoplasmin skin testing is:

Obsolete for routine ophthalmic diagnosis

and should not be used to establish POHS.

Fundus Photography

Fundus photography is useful for documenting:

• Histo spots
• Peripapillary atrophy
• Hemorrhage
• Pigmentary change
• Scar progression

Optical Coherence Tomography

OCT is the key modern structural test when MNV is suspected.

It may demonstrate:

• Subretinal hyperreflective material
• Subretinal fluid
• Intraretinal fluid
• RPE elevation
• Fibrosis
• Outer retinal atrophy

OCT is also useful for monitoring response to anti-VEGF therapy.

OCT Angiography

OCTA can demonstrate a neovascular network without intravenous dye.

It is useful for:

• Detecting MNV
• Monitoring vascular activity
• Assessing lesions when fluorescein angiography is undesirable

However, OCTA should be interpreted alongside:

• Structural OCT
• Clinical examination

because visible flow does not always indicate active exudation.

Fluorescein Angiography

FA may show:

• Early hyperfluorescence of classic MNV
• Progressive leakage in active lesions
• Window defects corresponding to atrophic histo spots

It remains useful when:

• Diagnosis is uncertain
• Lesion activity needs clarification

Indocyanine Green Angiography

ICG is rarely required for routine POHS.

It may be useful when:

• Choroidal pathology is atypical
• Differential diagnosis remains uncertain

Differential Diagnosis

Important differentials include:

• Multifocal choroiditis with panuveitis
• Punctate inner choroidopathy
• Pathologic myopia
• Age-related macular degeneration
• Angioid streaks
• Idiopathic MNV
• Other causes of multifocal chorioretinal scars
• Ocular toxoplasmosis
• Ocular tuberculosis
• Syphilitic chorioretinitis
• Active fungal chorioretinitis

POHS vs Multifocal Choroiditis

This distinction is particularly important.

POHS

Typically:

• Punched-out scars
• Peripapillary atrophy
• No vitritis
• MNV may occur

Multifocal Choroiditis with Panuveitis

Typically:

• Similar punched-out lesions
• Vitritis present
• May have anterior chamber inflammation
• Often inflammatory symptoms
• MNV may also occur

The presence of intraocular inflammation argues strongly against classic POHS.

POHS vs Punctate Inner Choroidopathy

PIC usually occurs in:

• Young myopic women

and produces:

• Small yellow-white posterior pole lesions
• Little or no vitritis
• High risk of MNV

Unlike POHS, PIC generally lacks the classic combination of:

• Widespread histo spots
• Peripapillary atrophy
• Endemic Histoplasma association

POHS vs Pathologic Myopia

Myopic MNV occurs in eyes with:

• High axial myopia
• Tessellated fundus
• Lacquer cracks
• Posterior staphyloma
• Myopic macular degeneration

These structural findings distinguish it from typical POHS.

POHS vs AMD

AMD generally occurs in older adults and is associated with:

• Drusen
• Pigment epithelial abnormalities
• Geographic atrophy

POHS typically lacks:

Drusen as the central disease feature

and occurs in a younger population.

Active Histoplasma Chorioretinitis

An important distinction:

Classic POHS is not the same as active ocular histoplasmosis in an immunocompromised patient.

Disseminated histoplasmosis can occasionally produce:

• Active chorioretinitis
• Systemic illness
• Multiorgan infection

especially in:

• Advanced HIV
• Transplant recipients
• Other severely immunosuppressed patients

These patients require systemic infectious-disease evaluation and antifungal therapy.

Treatment

Inactive POHS Without MNV

No treatment is required for:

• Inactive histo spots
• Stable peripapillary atrophy
• Asymptomatic scars

Management consists of:

• Observation
• Patient education
• Surveillance for MNV

Antifungal Therapy

Antifungal treatment is not indicated for classic POHS.

The ocular syndrome does not represent proven active fungal replication.

Antifungal therapy is reserved for:

Active systemic or ocular histoplasmosis, not presumed ocular histoplasmosis syndrome.

Corticosteroids

Routine corticosteroid treatment is:

Not recommended for typical POHS

because the classic syndrome lacks active intraocular inflammation.

If active inflammatory choroiditis is present, reconsider whether the diagnosis is actually:

• Multifocal choroiditis
• PIC
• Infectious choroiditis
• Another inflammatory disorder

rather than classic POHS.

Treatment of MNV

The modern first-line treatment for POHS-associated MNV is:

Intravitreal anti-VEGF therapy

Anti-VEGF Therapy

Agents used include:

• Bevacizumab
• Ranibizumab
• Aflibercept
• Other approved anti-VEGF agents depending on region and availability

Treatment usually produces:

• Reduction in fluid
• Reduction in hemorrhage
• Stabilization or improvement of visual acuity

Treatment Strategy

Treatment is individualized using:

• OCT evidence of activity
• Visual acuity
• Hemorrhage
• Symptoms

Many patients require:

• Several initial injections
• Followed by PRN or treat-and-extend style monitoring

The exact strategy depends on lesion behavior.

Anti-VEGF Prognosis

POHS-associated MNV often responds:

Very well to anti-VEGF therapy

particularly when detected early before:

• Foveal fibrosis
• Extensive atrophy

Thermal Laser

Thermal laser photocoagulation was historically used for:

• Extrafoveal MNV

but it is now rarely used because:

Anti-VEGF therapy provides superior anatomic flexibility and avoids immediate laser scotoma.

Photodynamic Therapy

Verteporfin PDT was also used historically.

It has largely been superseded by:

Anti-VEGF therapy

but may occasionally have a role in unusual refractory cases.

Submacular Surgery

Surgical removal of MNV was historically attempted.

It is now:

Obsolete for routine POHS-associated MNV

because anti-VEGF therapy provides better risk-benefit balance.

Follow-Up

Patients with inactive POHS should have periodic examination.

Frequency depends on:

• Presence of macular scars
• Fellow-eye history of MNV
• Symptoms
• Age
• Other macular disease

Annual follow-up is reasonable for many stable patients.

Higher-Risk Follow-Up

More frequent review is appropriate when there is:

• Previous MNV
• Macular histo spot
• Recent new symptoms
• Suspicious OCT changes
• Fellow-eye neovascular disease

Home Monitoring

Patients should monitor central vision using:

• Amsler grid
• Preferably monocularly

They should report immediately:

• New distortion
• Wavy lines
• Central blur
• Missing areas
• New scotoma

Prognosis

Patients without MNV usually maintain:

Excellent vision

because peripheral histo spots are often visually insignificant.

Visual prognosis depends primarily on:

• Development of MNV
• Location relative to fovea
• Speed of diagnosis
• Response to anti-VEGF
• Degree of residual fibrosis or atrophy

Fellow-Eye Risk

Patients who develop MNV in one eye are at increased risk of:

• MNV in the fellow eye

especially if the fellow eye contains:

• Macular histo spots

Long-term bilateral surveillance is therefore important.

Complications

The principal complication is:

Macular neovascularization

which can cause:

• Subretinal hemorrhage
• Exudation
• Fibrosis
• Disciform scar
• Permanent central visual loss

Other POHS lesions usually remain stable.

Ophthalmology Pearls

• POHS is diagnosed clinically by punched-out chorioretinal scars, peripapillary atrophy, and absence of vitritis.
• The classic lesions are called histo spots.
• POHS is strongly associated epidemiologically with prior Histoplasma capsulatum exposure, especially in the Ohio and Mississippi River valleys, but direct fungal causation within the eye is usually unproven.
• No vitreous inflammation is a key diagnostic feature; vitritis should make you reconsider multifocal choroiditis or another inflammatory/infectious process.
• Most patients are asymptomatic until macular neovascularization develops.
• MNV is the major cause of vision loss in POHS.
• Macular histo spots increase the risk of subsequent MNV.
• Routine Histoplasma serology, urine antigen, and skin testing are not useful for diagnosing classic POHS.
• OCT is central for detecting and monitoring MNV; OCTA and FA are useful adjuncts.
• Intravitreal anti-VEGF therapy is first-line treatment for POHS-associated MNV.
• Thermal laser, PDT, and submacular surgery are largely historical treatments in the anti-VEGF era.
• Antifungal therapy is not indicated for classic POHS, because it is not considered active ocular fungal infection.
• Classic POHS should be distinguished from disseminated histoplasmosis with active chorioretinitis in immunocompromised patients, which requires systemic antifungal treatment.
• Stable POHS without MNV requires observation, periodic follow-up, and home central-vision monitoring.
• New metamorphopsia or central blur should prompt urgent OCT evaluation for MNV.

Important Modern Concept The association between POHS and Histoplasma capsulatum is strong epidemiologically but remains: Presumed rather than microbiologically proven in most affected eyes. Classic POHS is not considered an active fungal infection of the eye. Therefore:  Antifungal therapy is not indicated for typical POHS Corticosteroids are not routine treatment Management is directed primarily toward MNV detection and treatment

Epidemiology POHS is most strongly associated with areas where H. capsulatum is endemic, particularly in the United States:  Ohio River Valley Mississippi River Valley Parts of the central and eastern United States  Many people in endemic regions have been exposed to Histoplasma without developing POHS. Only a small proportion develop the characteristic ocular phenotype.

Histoplasma Exposure Histoplasma capsulatum is a dimorphic fungus found particularly in soil contaminated by:  Bird droppings Bat droppings  Exposure may occur around:  Caves Chicken coops Old buildings Demolition sites Excavation Soil disruption  Most infections are:  Asymptomatic Mild respiratory infections  The ocular syndrome may become clinically apparent long after the presumed systemic exposure.

Pathogenesis The precise mechanism remains uncertain. A proposed sequence is: Prior systemic Histoplasma exposure → hematogenous seeding or immune-mediated choroidal injury → healed focal chorioretinal scars → later MNV in susceptible lesions However, viable fungal organisms are generally not demonstrable in classic POHS lesions. Thus the current concept favors:  Prior infectious trigger Subsequent inflammatory/chorioretinal scarring Late neovascular complications  rather than chronic active fungal infection.

Genetics Certain HLA associations have historically been reported, suggesting that: Host immune susceptibility may influence the development of POHS after Histoplasma exposure. Routine genetic testing has no clinical role.

Clinical Presentation Patients may be: Completely asymptomatic if lesions are peripheral or inactive. Symptoms usually arise when MNV develops near the macula. These may include:  Metamorphopsia Central blur Paracentral scotoma Micropsia Reduced central vision

Laterality POHS may be:  Unilateral clinically Bilateral  Even when symptoms occur in only one eye, the fellow eye may show:  Histo spots Peripapillary atrophy

Classic Fundus Triad The classic triad is:  Punched-out chorioretinal scars Peripapillary atrophy No vitritis  The absence of vitreous inflammation is particularly important diagnostically.

Histo Spots Histo spots are small, discrete, round or oval areas of:  Chorioretinal atrophy RPE disturbance  They are commonly:  Yellow-white when relatively fresh Pigmented or atrophic when healed  They may occur in:  Macula Midperiphery Peripheral retina

Macular Histo Spots Macular histo spots are clinically important because they increase the risk of: Secondary MNV which is the major cause of severe visual loss in POHS.

Peripapillary Atrophy Typical peripapillary findings include:  Circumferential or irregular chorioretinal atrophy Pigmentary alteration adjacent to the optic nerve  This may be subtle or extensive.

Histo Streaks Linear chorioretinal scars may occasionally be seen and have historically been called: Histo streaks These are less diagnostically important than the classic triad.

Absence of Inflammation Classic POHS lacks:  Anterior chamber cells Vitreous cells Vitreous haze  This feature helps distinguish it from inflammatory disorders such as: Multifocal choroiditis with panuveitis

Macular Neovascularization MNV may develop adjacent to:  Macular histo spots Peripapillary scars  Typical manifestations include:  Gray-green subretinal lesion Subretinal hemorrhage Intraretinal or subretinal fluid Lipid exudation Pigment epithelial detachment Fibrosis

Peripapillary MNV POHS may also produce: Peripapillary MNV which can enlarge toward:  Papillomacular bundle Fovea  and become visually significant.

Disciform Scar Untreated or chronic MNV may evolve into:  Fibrovascular scar Disciform macular scar  causing permanent central vision loss.

Diagnosis POHS is a: Clinical diagnosis There is no laboratory test that confirms classic ocular disease. Diagnosis rests on:  Characteristic fundus findings Lack of vitreous inflammation Compatible epidemiologic history Imaging when MNV is suspected

Laboratory Testing Routine testing for:  Histoplasma antibodies Serum antigen Urine antigen  is generally: Not useful for isolated POHS because these tests are designed primarily for diagnosing active systemic histoplasmosis.

Histoplasmin Skin Testing Histoplasmin skin testing is: Obsolete for routine ophthalmic diagnosis and should not be used to establish POHS.

Fundus Photography Fundus photography is useful for documenting:  Histo spots Peripapillary atrophy Hemorrhage Pigmentary change Scar progression

Optical Coherence Tomography OCT is the key modern structural test when MNV is suspected. It may demonstrate:  Subretinal hyperreflective material Subretinal fluid Intraretinal fluid RPE elevation Fibrosis Outer retinal atrophy  OCT is also useful for monitoring response to anti-VEGF therapy.

OCT Angiography OCTA can demonstrate a neovascular network without intravenous dye. It is useful for:  Detecting MNV Monitoring vascular activity Assessing lesions when fluorescein angiography is undesirable  However, OCTA should be interpreted alongside:  Structural OCT Clinical examination  because visible flow does not always indicate active exudation.

Fluorescein Angiography FA may show:  Early hyperfluorescence of classic MNV Progressive leakage in active lesions Window defects corresponding to atrophic histo spots  It remains useful when:  Diagnosis is uncertain Lesion activity needs clarification

Indocyanine Green Angiography ICG is rarely required for routine POHS. It may be useful when:  Choroidal pathology is atypical Differential diagnosis remains uncertain

Differential Diagnosis Important differentials include:  Multifocal choroiditis with panuveitis Punctate inner choroidopathy Pathologic myopia Age-related macular degeneration Angioid streaks Idiopathic MNV Other causes of multifocal chorioretinal scars Ocular toxoplasmosis Ocular tuberculosis Syphilitic chorioretinitis Active fungal chorioretinitis

POHS vs Multifocal Choroiditis This distinction is particularly important. POHS Typically:  Punched-out scars Peripapillary atrophy No vitritis MNV may occur  Multifocal Choroiditis with Panuveitis Typically:  Similar punched-out lesions Vitritis present May have anterior chamber inflammation Often inflammatory symptoms MNV may also occur  The presence of intraocular inflammation argues strongly against classic POHS.

POHS vs Punctate Inner Choroidopathy PIC usually occurs in:  Young myopic women  and produces:  Small yellow-white posterior pole lesions Little or no vitritis High risk of MNV  Unlike POHS, PIC generally lacks the classic combination of:  Widespread histo spots Peripapillary atrophy Endemic Histoplasma association

POHS vs Pathologic Myopia Myopic MNV occurs in eyes with:  High axial myopia Tessellated fundus Lacquer cracks Posterior staphyloma Myopic macular degeneration  These structural findings distinguish it from typical POHS.

POHS vs AMD AMD generally occurs in older adults and is associated with:  Drusen Pigment epithelial abnormalities Geographic atrophy  POHS typically lacks: Drusen as the central disease feature and occurs in a younger population.

Active Histoplasma Chorioretinitis An important distinction: Classic POHS is not the same as active ocular histoplasmosis in an immunocompromised patient. Disseminated histoplasmosis can occasionally produce:  Active chorioretinitis Systemic illness Multiorgan infection  especially in:  Advanced HIV Transplant recipients Other severely immunosuppressed patients  These patients require systemic infectious-disease evaluation and antifungal therapy.

Treatment Inactive POHS Without MNV No treatment is required for:  Inactive histo spots Stable peripapillary atrophy Asymptomatic scars  Management consists of:  Observation Patient education Surveillance for MNV

Antifungal Therapy Antifungal treatment is not indicated for classic POHS. The ocular syndrome does not represent proven active fungal replication. Antifungal therapy is reserved for: Active systemic or ocular histoplasmosis, not presumed ocular histoplasmosis syndrome.

Corticosteroids Routine corticosteroid treatment is: Not recommended for typical POHS because the classic syndrome lacks active intraocular inflammation. If active inflammatory choroiditis is present, reconsider whether the diagnosis is actually:  Multifocal choroiditis PIC Infectious choroiditis Another inflammatory disorder  rather than classic POHS.

Treatment of MNV The modern first-line treatment for POHS-associated MNV is: Intravitreal anti-VEGF therapy

Anti-VEGF Therapy Agents used include:  Bevacizumab Ranibizumab Aflibercept Other approved anti-VEGF agents depending on region and availability  Treatment usually produces:  Reduction in fluid Reduction in hemorrhage Stabilization or improvement of visual acuity

Treatment Strategy Treatment is individualized using:  OCT evidence of activity Visual acuity Hemorrhage Symptoms  Many patients require:  Several initial injections Followed by PRN or treat-and-extend style monitoring  The exact strategy depends on lesion behavior.

Anti-VEGF Prognosis POHS-associated MNV often responds: Very well to anti-VEGF therapy particularly when detected early before:  Foveal fibrosis Extensive atrophy

Thermal Laser Thermal laser photocoagulation was historically used for:  Extrafoveal MNV  but it is now rarely used because: Anti-VEGF therapy provides superior anatomic flexibility and avoids immediate laser scotoma.

Photodynamic Therapy Verteporfin PDT was also used historically. It has largely been superseded by: Anti-VEGF therapy but may occasionally have a role in unusual refractory cases.

Submacular Surgery Surgical removal of MNV was historically attempted. It is now: Obsolete for routine POHS-associated MNV because anti-VEGF therapy provides better risk-benefit balance.

Follow-Up Patients with inactive POHS should have periodic examination. Frequency depends on:  Presence of macular scars Fellow-eye history of MNV Symptoms Age Other macular disease  Annual follow-up is reasonable for many stable patients.

Higher-Risk Follow-Up More frequent review is appropriate when there is:  Previous MNV Macular histo spot Recent new symptoms Suspicious OCT changes Fellow-eye neovascular disease

Home Monitoring Patients should monitor central vision using:  Amsler grid Preferably monocularly  They should report immediately:  New distortion Wavy lines Central blur Missing areas New scotoma

Prognosis Patients without MNV usually maintain: Excellent vision because peripheral histo spots are often visually insignificant. Visual prognosis depends primarily on:  Development of MNV Location relative to fovea Speed of diagnosis Response to anti-VEGF Degree of residual fibrosis or atrophy

Fellow-Eye Risk Patients who develop MNV in one eye are at increased risk of:  MNV in the fellow eye  especially if the fellow eye contains:  Macular histo spots  Long-term bilateral surveillance is therefore important.

Complications The principal complication is: Macular neovascularization which can cause:  Subretinal hemorrhage Exudation Fibrosis Disciform scar Permanent central visual loss  Other POHS lesions usually remain stable.

Ophthalmology Pearls  POHS is diagnosed clinically by punched-out chorioretinal scars, peripapillary atrophy, and absence of vitritis. The classic lesions are called histo spots. POHS is strongly associated epidemiologically with prior Histoplasma capsulatum exposure, especially in the Ohio and Mississippi River valleys, but direct fungal causation within the eye is usually unproven. No vitreous inflammation is a key diagnostic feature; vitritis should make you reconsider multifocal choroiditis or another inflammatory/infectious process. Most patients are asymptomatic until macular neovascularization develops. MNV is the major cause of vision loss in POHS. Macular histo spots increase the risk of subsequent MNV. Routine Histoplasma serology, urine antigen, and skin testing are not useful for diagnosing classic POHS. OCT is central for detecting and monitoring MNV; OCTA and FA are useful adjuncts. Intravitreal anti-VEGF therapy is first-line treatment for POHS-associated MNV. Thermal laser, PDT, and submacular surgery are largely historical treatments in the anti-VEGF era. Antifungal therapy is not indicated for classic POHS, because it is not considered active ocular fungal infection. Classic POHS should be distinguished from disseminated histoplasmosis with active chorioretinitis in immunocompromised patients, which requires systemic antifungal treatment. Stable POHS without MNV requires observation, periodic follow-up, and home central-vision monitoring. New metamorphopsia or central blur should prompt urgent OCT evaluation for MNV.