Ophthalmology – Phacoanaphylactic Glaucoma

Basics

Description

Phacoanaphylactic glaucoma is an older term for secondary glaucoma occurring with phacoantigenic uveitis, an immune-mediated granulomatous inflammation directed against exposed lens proteins after disruption of the lens capsule.

Preferred modern terminology includes:

• Phacoantigenic uveitis
• Lens-induced uveitis with secondary glaucoma

The historical term phacoanaphylactic endophthalmitis is misleading because the reaction is not a true IgE-mediated anaphylactic process.

The disorder typically follows:

• Cataract surgery with retained lens material
• Penetrating or blunt trauma causing lens capsule rupture
• Rare spontaneous lens capsule disruption

Clinical Importance

The characteristic clinical combination is:

Persistent granulomatous anterior uveitis + elevated IOP after disruption of the lens capsule

The principal management goals are to:

1. Suppress inflammation.
2. Control IOP.
3. Identify and remove residual lens material when present.
4. Exclude infectious postoperative endophthalmitis.

Epidemiology

The condition is uncommon in modern cataract surgery because of:

• Improved phacoemulsification
• Better removal of cortical material
• Smaller incisions
• Improved vitreoretinal management of dropped lens fragments

It is more likely after:

• Complicated cataract surgery
• Posterior capsule rupture
• Retained lens fragments
• Lens trauma

Terminology

Several lens-induced inflammatory glaucomas must be distinguished.

Phacoantigenic Uveitis

• Immune-mediated granulomatous inflammation
• Requires lens capsule disruption
• Usually follows surgery or trauma
• Secondary glaucoma may occur

Lens-Particle Glaucoma

• Trabecular obstruction by lens particles and inflammatory cells
• Usually after surgery or trauma
• Less dependent on a specific immune sensitization mechanism

Phacolytic Glaucoma

• Occurs with a hypermature cataract
• Capsule is usually grossly intact
• Leakage of high-molecular-weight lens proteins produces macrophage-mediated trabecular obstruction

These entities may overlap clinically.

Pathophysiology

Normally, lens proteins are relatively sequestered from the immune system.

When the capsule is disrupted:

Lens proteins become exposed to the immune system

This can trigger a:

• Delayed immune response
• Granulomatous inflammatory reaction

Histologically, inflammation develops around lens material.

Mechanism of Glaucoma

IOP may rise because of:

• Inflammatory cells obstructing the trabecular meshwork
• Macrophages containing lens material
• Free lens particles
• Lens proteins
• Trabeculitis
• Peripheral anterior synechiae
• Posterior synechiae with secondary pupillary block in selected cases
• Steroid response during treatment

Therefore the glaucoma may be:

• Open-angle
• Secondary angle-closure
• Mixed mechanism

Etiology

Typical precipitating events include:

• Cataract surgery
• Posterior capsule rupture
• Dropped nuclear fragments
• Retained cortical material
• Penetrating ocular trauma
• Traumatic lens rupture

Rarely, spontaneous capsular rupture may occur.

History

Ask specifically about:

• Recent cataract surgery
• Complicated phacoemulsification
• Posterior capsule rupture
• Retained lens fragments
• Pars plana vitrectomy
• Ocular trauma
• Previous episodes of uveitis

Symptoms may include:

• Ocular pain
• Photophobia
• Redness
• Blurred vision
• Halos
• Headache if IOP is markedly elevated

Timing

Presentation may occur:

• Days
• Weeks
• Occasionally longer

after lens capsule disruption.

Persistent or recurrent postoperative inflammation should raise suspicion for:

• Retained lens material
• Phacoantigenic uveitis
• Chronic postoperative endophthalmitis
• TASS

Physical Examination

Typical findings include:

• Ciliary injection
• Anterior chamber cells and flare
• Granulomatous inflammation
• Mutton-fat keratic precipitates
• Posterior synechiae
• Elevated IOP
• Visible lens fragments in some cases

Granulomatous Uveitis

Inflammation may be characterized by:

• Large keratic precipitates
• Iris nodules occasionally
• Posterior synechiae
• Significant anterior chamber cellular reaction

The inflammation may persist until the inciting lens material is removed.

Lens Material

Residual lens material may be found:

• In the anterior chamber
• In the capsular bag
• Behind the iris
• In the vitreous cavity

Posteriorly retained lens fragments can be difficult to visualize directly.

Posterior Segment Findings

If lens material has dropped posteriorly, there may be:

• Vitritis
• Retained nuclear fragment
• Cystoid macular edema
• Retinal edema
• Reduced fundus view

Intraocular Pressure

IOP may range from mildly elevated to:

Severely elevated

Mechanisms include:

• Trabecular inflammatory obstruction
• Lens-particle obstruction
• Peripheral anterior synechiae
• Steroid response

Diagnostic Approach

The key questions are:

1. Is retained lens material present?
2. Is this sterile inflammation or infection?
3. What mechanism is causing the elevated IOP?
4. Is there posterior segment involvement?

Slit-Lamp Examination

Evaluate for:

• Corneal edema
• Keratic precipitates
• Anterior chamber cell/flare
• Hypopyon
• Lens fragments
• Posterior synechiae
• Surgical wound integrity

Gonioscopy

When feasible, gonioscopy may demonstrate:

• Lens material in the angle
• Trabecular inflammatory debris
• Peripheral anterior synechiae
• Secondary angle closure

Dilated Fundus Examination

Assess for:

• Dropped lens fragments
• Vitritis
• Retinal inflammation
• Cystoid macular edema
• Retinal tears or detachment after complicated surgery

B-Scan Ultrasonography

B-scan is useful when the posterior segment cannot be visualized because of:

• Corneal edema
• Severe inflammation
• Media opacity

It may help identify:

• Retained lens fragments
• Vitreous opacities
• Retinal detachment

Anterior Segment Imaging

UBM or AS-OCT may occasionally help detect:

• Retained anterior lens material
• Angle abnormalities
• Capsular remnants

particularly when fragments are hidden behind the iris.

Aqueous or Vitreous Sampling

Sampling is not routinely required for classic sterile phacoantigenic inflammation.

It becomes important when:

Infectious endophthalmitis cannot be excluded.

Possible tests include:

• Gram stain
• Culture
• PCR in selected cases

Histopathology

Classic histology demonstrates:

• Polymorphonuclear leukocytes
• Epithelioid histiocytes
• Multinucleated giant cells

arranged around:

Lens material

This produces a zonal granulomatous inflammatory pattern.

Differential Diagnosis

Important differentials include:

• Lens-particle glaucoma
• Phacolytic glaucoma
• Chronic postoperative endophthalmitis
• Toxic anterior segment syndrome
• Exacerbation of preexisting uveitis
• Retained lens fragments without immune granulomatous reaction
• Sympathetic ophthalmia
• Uveitic glaucoma from another cause

Chronic Postoperative Endophthalmitis

One of the most important mimics is indolent infection, particularly from:

Cutibacterium acnes

formerly Propionibacterium acnes.

Clues include:

• Recurrent inflammation after steroid taper
• White plaque within the capsular bag
• Vitritis
• Chronic postoperative course

Infection must be excluded before assuming the process is purely immune-mediated.

Toxic Anterior Segment Syndrome

TASS usually presents:

• Within approximately 12–48 hours after surgery
• With diffuse limbus-to-limbus corneal edema
• Marked anterior chamber inflammation
• Minimal pain
• No significant vitritis

It results from:

Sterile toxic injury, not lens-protein sensitization.

Phacolytic Glaucoma

Phacolytic glaucoma generally occurs in an eye with:

• Mature or hypermature cataract
• Intact-appearing capsule
• High IOP
• Anterior chamber inflammation

Macrophages and lens proteins obstruct the trabecular meshwork.

Definitive treatment is:

Cataract extraction

after initial IOP control.

Lens-Particle Glaucoma

Lens-particle glaucoma occurs when:

• Lens fragments physically enter the anterior chamber

usually after:

• Trauma
• Cataract surgery

It may resemble phacoantigenic uveitis but is primarily a:

Mechanical-inflammatory trabecular obstruction

rather than a classic granulomatous immune response.

Treatment Principles

Management consists of:

1. Control inflammation.
2. Lower IOP.
3. Remove retained lens material.
4. Treat complications.

Definitive control often requires:

Removal of the inciting lens material.

Topical Corticosteroids

Topical corticosteroids are first-line for ocular inflammation.

Examples include:

• Prednisolone acetate
• Difluprednate in selected severe cases

Dosing depends on severity and may initially be frequent.

Steroids should subsequently be:

Tapered according to clinical response

after definitive treatment.

Cycloplegic Therapy

Cycloplegics may be useful when there is:

• Significant ciliary spasm
• Pain
• Posterior synechiae

Examples include:

• Cyclopentolate
• Atropine in more severe disease

IOP-Lowering Therapy

Aqueous suppressants are generally preferred.

Options include:

• Topical beta-blockers
• Topical carbonic anhydrase inhibitors
• Alpha-2 agonists
• Oral acetazolamide when needed

Hyperosmotic Therapy

For severe acute IOP elevation, temporary treatment may include:

• IV mannitol
• Oral hyperosmotic agents in selected patients

This is generally a bridge to definitive treatment rather than long-term therapy.

Prostaglandin Analogs

Prostaglandin analogs may lower IOP but are often used cautiously during:

• Active severe uveitis
• Significant cystoid macular edema

They are not absolutely contraindicated in every inflammatory glaucoma but are often not the first choice during active postoperative inflammation.

Miotics

Miotics are generally avoided because they may:

• Worsen inflammation
• Promote posterior synechiae
• Increase ciliary spasm

Surgical Removal of Lens Material

The definitive treatment is:

Removal of retained lens material when clinically significant.

The surgical approach depends on location.

Anterior Segment Lens Fragments

Fragments in the:

• Anterior chamber
• Capsular bag
• Anterior vitreous

may be removed by an:

Anterior segment surgeon

using irrigation/aspiration or other appropriate techniques.

Posteriorly Retained Lens Fragments

Posteriorly displaced nuclear fragments usually require:

Pars plana vitrectomy

by a vitreoretinal surgeon.

Surgery may include:

• Vitrectomy
• Removal of lens fragments
• Fragmatome-assisted removal for dense nuclear material

Timing of Vitrectomy

Timing depends on:

• Fragment size
• Degree of inflammation
• IOP
• Corneal edema
• Macular status

Significant retained nuclear material with:

• Severe inflammation
• Uncontrolled IOP
• Persistent corneal edema

generally favors timely vitreoretinal intervention.

Cystoid Macular Edema

CME may accompany chronic postoperative inflammation.

Treatment may include:

• Topical corticosteroids
• Topical NSAIDs
• Periocular or intraocular corticosteroids in selected cases

after infection has been excluded.

Persistent Glaucoma

IOP may remain elevated after lens removal because of:

• Trabecular damage
• Peripheral anterior synechiae
• Steroid response
• Chronic uveitic glaucoma

Long-term glaucoma therapy may therefore be necessary.

Glaucoma Surgery

If IOP remains uncontrolled despite:

• Lens removal
• Control of inflammation
• Maximal tolerated medical treatment

surgery may be required.

Options include:

• Glaucoma drainage device
• Trabeculectomy in selected eyes
• Cyclophotocoagulation in refractory disease

In uveitic eyes, drainage devices are frequently important because filtration surgery may fail from inflammation and scarring.

Follow-Up

During active disease, follow-up should be:

Frequent

depending on:

• IOP
• Degree of inflammation
• Corneal edema
• Retained lens material
• Response to therapy

Some patients require review every:

• Day
• Few days

until stable.

Long-Term Monitoring

After inflammation resolves, monitor for:

• Persistent glaucoma
• Peripheral anterior synechiae
• Steroid-induced ocular hypertension
• Cystoid macular edema
• Optic nerve damage

Prognosis

Prognosis depends on:

• Duration of inflammation
• Magnitude of IOP elevation
• Amount and location of retained lens material
• Corneal damage
• Macular involvement
• Timing of definitive treatment

Prompt recognition and removal of significant retained material generally improves outcome.

Complications

Potential complications include:

• Secondary glaucoma
• Permanent optic nerve damage
• Peripheral anterior synechiae
• Posterior synechiae
• Cystoid macular edema
• Corneal edema
• Chronic uveitis
• Vitreous inflammation
• Surgical complications from vitrectomy or glaucoma surgery

Ophthalmology Pearls

• “Phacoanaphylactic glaucoma” is an older term; the preferred modern concept is phacoantigenic uveitis with secondary glaucoma.
• It occurs after lens capsule disruption, most commonly from cataract surgery or trauma.
• The inflammatory reaction is granulomatous and directed against exposed lens proteins, not a true anaphylactic reaction.
• Think of it in a patient with persistent granulomatous uveitis and elevated IOP after complicated cataract surgery or lens trauma.
• Retained lens fragments may be located in the anterior chamber or vitreous cavity.
• Removal of clinically significant retained lens material is the definitive treatment.
• Posteriorly dropped nuclear fragments usually require pars plana vitrectomy.
• Use topical corticosteroids plus aqueous-suppressant glaucoma therapy while arranging definitive management.
• Avoid routine miotics during active inflammation.
• Always distinguish this disorder from chronic postoperative endophthalmitis, especially Cutibacterium acnes infection.
• Also distinguish it from phacolytic glaucoma, in which the capsule is generally intact and hypermature lens proteins leak into the anterior chamber.
• Persistent IOP elevation after inflammation resolves may reflect permanent trabecular damage or synechial angle closure and can require long-term glaucoma treatment or surgery.