Phacoanaphylactic Uveitis
1. What is Phacoanaphylactic Endophthalmitis?
Section titled “1. What is Phacoanaphylactic Endophthalmitis?”Phacoanaphylactic endophthalmitis (Phacoanaphylactic Uveitis) is a persistent granulomatous anterior uveitis caused by a type III allergic reaction (immune complex type) to lens proteins. It develops as an immune response to lens proteins leaking from a damaged lens capsule due to trauma or surgery, spontaneous rupture of a hypermature cataract, or a dislocated lens in the vitreous. It often occurs 1 to 14 days after surgery or trauma.
In English literature, it is also called “Phacoanaphylactic Endophthalmitis,” “Phacoanaphylaxis,” or “Lens-induced Granulomatous Uveitis.” It is a subtype of lens-induced uveitis (LIU) 1).
Inflammation may persist after cataract surgery. According to the US IRIS Registry (7,513,604 cases), the incidence of persistent uveitis after cataract surgery was 1.68% 3).
Position of This Disease in Lens-Induced Uveitis
Section titled “Position of This Disease in Lens-Induced Uveitis”Lens-induced uveitis (LIU) is classified into the following three subtypes.
- Phacoanaphylactic uveitis (this disease): Type III allergic reaction (immune complex type). Severe granulomatous anterior uveitis. Characterized by mutton-fat keratic precipitates. May be complicated by secondary glaucoma.
- Phacolytic uveitis: Primarily involves physical obstruction by macrophages. Inflammatory findings are relatively mild. Non-granulomatous to weakly granulomatous.
- Inflammation due to retained lens material: Acute inflammation caused by residual cortical material after surgery.
This disease is fundamentally different from phacolytic uveitis in terms of immune mechanism and pathological findings. It is characterized by strong granulomatous inflammation due to type III allergy (immune complex type), and the presence or absence of mutton-fat KP is an important differentiating point.
Epidemiology
Section titled “Epidemiology”- Occurs unilaterally4)
- No gender difference, no racial difference, no HLA association4)
- When caused by spontaneous liquefaction, it is mainly seen in elderly individuals4)
- Onset background: 1 to 14 days after lens damage due to trauma or surgery, spontaneous capsular rupture in hypermature cataract, dislocated lens into the vitreous
The immune mechanisms are fundamentally different. Lens-induced uveitis is a severe granulomatous inflammation caused by type III allergy (immune complex type), characterized by mutton-fat keratic precipitates. In contrast, phacolytic glaucoma involves macrophages phagocytosing free lens proteins, physically obstructing the trabecular meshwork, with inflammation being non-granulomatous to mildly granulomatous. Clinically, the presence of mutton-fat KP is an important finding suggestive of lens-induced uveitis.
2. Main symptoms and clinical findings
Section titled “2. Main symptoms and clinical findings”Subjective symptoms
Section titled “Subjective symptoms”- Ciliary injection (marked)
- Eye pain (associated with elevated intraocular pressure)
- Decreased visual acuity
Clinical findings
Section titled “Clinical findings”In lens-induced uveitis, ciliary injection, mutton-fat keratic precipitates, anterior chamber cells and flare, and protein are observed. The clinical features of lens-induced uveitis and phacolytic glaucoma are compared below.
| Feature | Lens-induced uveitis | Phacolytic glaucoma |
|---|---|---|
| Immune mechanism | Type III allergy (immune complex type) | Macrophage phagocytosis and obstruction |
| Keratic precipitates | Mutton-fat KP (granulomatous) | Fine KP (non-granulomatous) |
| Anterior chamber inflammation | Severe (with fibrin and hypopyon) | Mild to moderate |
| Mechanism of intraocular pressure elevation | Inflammatory trabecular meshwork obstruction | Physical obstruction by macrophages and protein |
| Onset timing | Most commonly 1–14 days postoperatively | Frequently spontaneous onset in hypermature cataract |
Other major clinical findings:
- Mutton-fat keratic precipitates (mutton-fat KP): Evidence of granulomatous inflammation. A characteristic finding of this disease4)
- Ciliary injection and conjunctival injection (marked)4)
- Anterior chamber inflammation (flare and cells, increased protein)
- Fibrin exudation
- Posterior synechiae
- Hypopyon (in severe cases)4)
- Elevated intraocular pressure (secondary glaucoma due to inflammatory obstruction of the trabecular meshwork)
- Vitreous opacity (when inflammation is severe)
- In the case of hypermature cataract, shimmering substances in the anterior chamber 4)
- After cataract surgery, residual lens nucleus and cortex are observed in the anterior chamber 4)
Most cases occur 1 to 14 days after surgery. There are also late-onset cases, sometimes within a few weeks. The timing differs when caused by spontaneous capsular rupture of hypermature cataract. The onset time also depends on the amount of residual lens material and the individual’s immune reactivity.
3. Causes and Risk Factors
Section titled “3. Causes and Risk Factors”Lens proteins normally exist as “sequestered antigens” immunologically. Since being enclosed within the lens capsule during embryonic development, they have no contact with the immune system. When the lens capsule is damaged, lens proteins are exposed to the aqueous humor and vitreous, triggering a type III allergic reaction (immune complex type).
Main risk factors:
- Traumatic rupture of the lens capsule (perforating ocular trauma)
- Residual cortex after cataract surgery (especially in cases of massive retention) 4)
- Spontaneous capsule rupture and liquefaction of hypermature cataract
- Lens dislocation into the vitreous cavity
Diabetes (IRR 1.87, 95% CI 1.84-1.90) and female sex (IRR 1.14, 95% CI 1.12-1.15) have been reported as risk factors for postoperative persistent uveitis 3). Diagnosis of IPICS requires exclusion of retained lens fragments, IOL malposition, herpetic eye disease, and other conditions 5).
Pathological findings: Granulomatous inflammation centered on the lens. Epithelioid cells and multinucleated giant cells accumulate around lens material. This pathological finding is an important histological distinguishing feature from phacolytic uveitis.
The overall prevalence of uveitis after cataract surgery is approximately 1.1–1.8%, and most cases are transient and resolve. The development of phacoanaphylactic endophthalmitis depends on individual immune susceptibility and the amount of residual lens material, so it does not occur in all cases.
4. Diagnosis and Examination Methods
Section titled “4. Diagnosis and Examination Methods”There are no clear diagnostic criteria4). If iridocyclitis findings appear within days to weeks after rupture of the lens capsule due to surgery or trauma, and residual lens components are clearly present, this condition can be diagnosed. Exposure of lens components into the anterior chamber and vitreous cavity is important for diagnosis4).
Standard Examinations
Section titled “Standard Examinations”- Slit-lamp microscopy: Confirmation of mutton-fat keratic precipitates, fibrin, posterior synechiae, and residual lens material
- Intraocular pressure measurement: Evaluation of secondary glaucoma
- Gonioscopy: Confirmation of glaucoma mechanism (presence of peripheral anterior synechiae)
- Bacteriological examination of aqueous humor and vitreous fluid: Differentiation from infectious endophthalmitis. Bacterial culture and PCR4)
- B-mode ultrasonography: Exclusion of retinal detachment and abscess, and evaluation of anterior vitreous opacity when fundus is not visible4)
- Histopathological examination of aqueous humor: Detection of lens components4)
- Western blot: Detection of lens-specific proteins in aqueous humor may aid diagnosis2)
- Systemic examination: White blood cell count, inflammatory markers, and blood glucose are often normal4)
Differential Diagnosis
Section titled “Differential Diagnosis”| Differential Disease | Key Points for Differentiation |
|---|---|
| Bacterial endophthalmitis (acute postoperative) | Within a few days postoperatively. Severe hypopyon and vitreous opacity. Culture positive |
| P. acnes delayed-onset endophthalmitis | Weeks to months post-surgery. White plaque on lens capsule. Cannot be ruled out even if bacteria are not detected. |
| TASS | Within 24 hours post-surgery. Diffuse corneal edema. Non-infectious. |
| Sympathetic ophthalmia | After penetrating ocular trauma. Bilateral. Sunset glow fundus. Exudative retinal detachment in the fundus. |
| Phacolytic glaucoma | Inflammatory findings are minimal, with elevated intraocular pressure as the main feature. Develops from hypermature cataract. |
In differentiation from sympathetic ophthalmia, key distinguishing points are that it is unilateral and that exudative retinal detachment rarely occurs in the fundus4).
Differentiation is made by bacterial culture and PCR of aqueous humor and vitreous. Pathological detection of lens components is also useful. Delayed-onset endophthalmitis caused by P. acnes is often difficult to diagnose based on clinical findings alone. Even if bacteria cannot be detected, infection cannot be completely ruled out, so comprehensive judgment is necessary. If infection cannot be ruled out, consider antibiotics after culture collection.
5. Standard Treatment
Section titled “5. Standard Treatment”Early diagnosis and initiation of treatment are most important. If a large amount of lens material remains, surgical removal of the lens material is essential and the most effective treatment.
Surgical Treatment (Curative Treatment)
Section titled “Surgical Treatment (Curative Treatment)”- Removal of residual lens material by phacoemulsification and aspiration (PEA): Curative treatment. First choice when a large amount remains.
- Intracapsular cataract extraction (ICCE) + anterior vitrectomy: In cases of hypermature cataract4).
- Anterior chamber irrigation + complete removal of residual cortex: When intraocular pressure is poorly controlled and anti-inflammatory drugs are ineffective4)
- If the residual lens material is very small, it may heal with observation alone4)
Preoperative anti-inflammatory therapy (bridging treatment) and pharmacotherapy
Section titled “Preoperative anti-inflammatory therapy (bridging treatment) and pharmacotherapy”The following are used during preoperative and conservative management.
| Stage | Treatment | Drugs/Procedures |
|---|---|---|
| 1. Preoperative anti-inflammatory therapy | Steroids + mydriatics + intraocular pressure-lowering drugs | Betamethasone 0.1% eye drops (4–6 times/day), atropine 1% eye drops (1–2 times/day), timolol 0.5% eye drops (2 times/day) |
| 2. Curative treatment | Surgical removal of retained lens material | PEA or ICCE ± anterior vitrectomy |
| 3. Conservative management | When small amount remains and spontaneous absorption is expected | Topical steroid (short-term). Avoid long-term use |
| 4. Refractory cases | When anti-inflammatory and intraocular pressure-lowering drugs are ineffective | Anterior chamber washout + complete removal of residual cortex |
Details of each medication:
- Steroid eye drops: 0.1% betamethasone sodium phosphate eye drops (4–6 times daily)
- Subconjunctival steroid injection: For severe inflammation (e.g., dexamethasone 2 mg)
- Mydriatic agents: 1% atropine sulfate eye drops (1–2 times daily) or 0.5% tropicamide eye drops (to prevent posterior synechiae and manage pupil)
- Beta-blocker eye drops: 0.5% timolol maleate (twice daily)
- Carbonic anhydrase inhibitors: 1% dorzolamide hydrochloride eye drops (3 times daily) or oral acetazolamide 250 mg (2–4 times daily)
If the residual amount is small and spontaneous absorption is expected, observation with topical steroids may be possible. However, if a large amount of lens material remains, surgical removal is the definitive treatment, and steroids alone are insufficient. Long-term steroid use carries risks of side effects such as increased intraocular pressure, so if the effect is inadequate, surgery should be considered promptly.
6. Pathophysiology and Detailed Mechanism
Section titled “6. Pathophysiology and Detailed Mechanism”Lens proteins are enclosed within the lens capsule during fetal development and exist as “sequestered antigens” without contact with the immune system. After lens capsule rupture, lens proteins (mainly alpha-crystallin, etc.) are exposed to the aqueous humor and vitreous, initiating the pathogenic mechanism.
Pathological process:
- Lens capsule rupture (trauma, surgery, spontaneous rupture of hypermature cataract) → lens proteins exposed to aqueous humor and vitreous
- Exposed lens proteins trigger a type III allergic reaction (immune complex-mediated reaction)
- Tissue deposition of immune complexes → complement activation → neutrophil infiltration → tissue damage
- If prolonged, granuloma formation by epithelioid cells and multinucleated giant cells
- Granulomatous inflammation spreads to the trabecular meshwork → impaired aqueous outflow → secondary glaucoma (phacoanaphylactic glaucoma)
- Persistent inflammation → risk of cyclitic membrane formation → danger of tractional retinal detachment
Pathophysiological difference from phacolytic glaucoma: Phacolytic glaucoma is a reaction in which macrophages phagocytose free lens proteins and physically obstruct the trabecular meshwork, and is not a type III allergic reaction. The hypersensitivity granulomatous inflammation is stronger, and the risk of prolonged and chronic inflammation is higher.
This disease is unilateral, and exudative retinal detachment in the fundus is rare4). The inflammation remaining unilateral is an important distinguishing point from sympathetic ophthalmia, which is bilateral.
7. Latest Research and Future Perspectives
Section titled “7. Latest Research and Future Perspectives”- Detection of lens-specific proteins in aqueous humor by Western blotting has been reported as a diagnostic aid (Tanito et al. 2009)2). In traumatic lens-induced uveitis, detecting lens-specific proteins such as alpha-crystallin and beta-crystallin in aqueous humor may provide objective diagnostic assistance.
- Large-scale epidemiological data from the US IRIS Registry (7,513,604 cases) on persistent postoperative uveitis after cataract surgery (PUPPI): incidence rate was 1.68%. Risk factors for persistent postoperative uveitis included diabetes (IRR 1.87, 95% CI 1.84-1.90) and female sex (IRR 1.14, 95% CI 1.12-1.15)3). Note that these data cover all types of postoperative uveitis after cataract surgery, not limited to lens-induced uveitis.
- A report on the diagnosis and management of idiopathic persistent iritis after cataract surgery (IPICS) proposes the concept of idiopathic persistent iritis after excluding residual lens fragments, IOL malposition, and history of herpetic eye disease5).
- The frequency of chronic postoperative uveitis varies among reports, and attention should be paid to differences in definitions and observation periods6).
8. References
Section titled “8. References”- Nche EN, Amer R. Lens-induced uveitis: an update. Graefes Arch Clin Exp Ophthalmol. 2020;258(7):1359-1365.
- Tanito M, Kaidzu S, Katsube T, Nonoyama S, Takai Y, Ohira A. Diagnostic Western blot for lens-specific proteins in aqueous fluid after traumatic lens-induced uveitis. Jpn J Ophthalmol. 2009;53(4):436-439. doi:10.1007/s10384-009-0671-x.
- Acharya B, Hyman L, Tomaiuolo M, Zhang Q, Dunn JP. Prolonged Undifferentiated Postoperative Pseudophakic Iridocyclitis. Ophthalmology. 2024.
- 日本眼炎症学会ぶどう膜炎診療ガイドライン作成委員会. ぶどう膜炎診療ガイドライン. 日眼会誌. 2019;123(6):635-696.
- Soifer M, Mousa HM, Jammal AA, et al. Diagnosis and management of idiopathic persistent iritis after cataract surgery (IPICS). Am J Ophthalmol. 2022;234:250-258.
- Patel C, Kim SJ, Chomsky A, Saboori M. Incidence and risk factors for chronic uveitis following cataract surgery. Ocul Immunol Inflamm. 2013;21(2):130-134.