Lens-induced uveitis (LIU) is a granulomatous uveitis caused by exposure of lens proteins, which normally have immune privilege, into the eye. It is also called “phacoanaphylactic endophthalmitis.” It was first reported by Verhoeff and Lemoine in 1919.
The frequency among all uveitis cases is extremely rare, less than 1% 1, 2); in one systematic review, only 6 out of 140 cases were clinically diagnosed. 1) With advances in modern cataract surgery techniques, the incidence is further decreasing.
This disease is broadly classified into the following two types based on the mechanism of onset. 1)
Phacogenic (Type IV)
Also known as: phacoantigenic uveitis
Mechanism: Rupture of the lens capsule leads to massive exposure of lens proteins into the anterior chamber, triggering a type IV (cell-mediated, delayed-type) hypersensitivity reaction.
Causes: Mainly due to capsule damage from trauma or surgery.
Phacolytic
They are different diseases. Infectious endophthalmitis is a purulent inflammation caused by pathogenic microorganisms such as bacteria or fungi, whereas LIU is a sterile granulomatous inflammation due to an immune reaction to lens proteins. However, their clinical presentations can be similar, requiring differentiation. See the Diagnosis and Testing section for details.
Onset is often acute to subacute, with symptoms occurring only in the affected eye.
Slit-lamp microscopy findings are fundamental for diagnosis.
Both appear as white deposits at the bottom of the anterior chamber and can be difficult to differentiate by slit-lamp alone. LIU pseudohypopyon originates from macrophages and lens proteins, and confirmation of sterility via aqueous humor culture is key for differentiation.
The lens is an immunologically privileged organ developmentally, and lens proteins are not recognized as “self” by the immune system.2) Normally, the lens capsule acts as a barrier, preventing an immune response. LIU occurs when this barrier is disrupted.
Clinical diagnosis of LIU is not easy; in one report, only 6 out of 140 observed cases were clinically diagnosed. 1)
Differential diagnosis from the following diseases is particularly important. 1, 2)
| Differential Disease | Key Points for Differentiation |
|---|---|
| Infectious Endophthalmitis | Culture positive, rapid progression |
| TASS | Immediately after surgery, sterile |
| Sympathetic Ophthalmia | Inflammation also in the fellow eye |
If it occurs immediately after surgery, postoperative endophthalmitis or TASS is also possible. On the other hand, if symptoms develop long after surgery, or if there is a history of hypermature cataract or ocular trauma, LIU should be suspected. UBM and aqueous humor analysis help in differentiation.
Cataract surgery (lens extraction) is the only curative treatment. 2) Glaucoma surgery alone, such as trabeculectomy, is ineffective because it cannot remove the causative material. 2)
Control inflammation and intraocular pressure as much as possible before surgery.
Intraocular pressure reduction (for hypermature cataract or high IOP cases): 2)
Preoperative anti-inflammatory therapy (for phacogenic types): 1)
Phacoemulsification (PEA)
Indications: Cases with an intact or partially damaged capsule and a soft to moderately hard nucleus.
Features: Simultaneous IOL insertion (in-the-bag or sulcus fixation). If retrolental opacity is present, anterior vitrectomy is combined. 1)
Postoperative outcomes: Reports have achieved corrected visual acuity of 20/25 at 2 months postoperatively. 1)
Extracapsular Cataract Extraction (ECCE/MSICS)
Indications: Hypermature/hard nuclear cataracts (Morgagnian cataract). 2)
Features: Manual extracapsular extraction using iris hooks and trypan blue staining. Safety of MSICS surgery has been reported. 2)
Postoperative outcomes: Reports have achieved corrected visual acuity of 20/40 at 1 month postoperatively. 2)
Phacoanaphylactic Glaucoma
Definition (EGS 5th edition): Secondary glaucoma associated with granulomatous inflammation to lens proteins. 3)
Treatment strategy: Trabeculectomy alone is ineffective. Lens extraction is essential. Perform cataract surgery after preoperative management with intraocular pressure-lowering medications. 2, 3)
The lens is an organ that acquired immune privilege during embryonic development. 2) Lens proteins (α, β, γ crystallins) are sequestered early in development, so they are not registered in the T-cell repertoire and are treated as “non-self” proteins. Normally, the lens capsule contains these proteins and prevents contact with the immune system.
When the capsule is physically damaged, lens proteins are massively exposed into the anterior chamber. Sensitized T cells are activated, leading to a CD4-positive helper T cell-driven type IV (delayed) hypersensitivity reaction. Pathologically, zonal granuloma is characteristic, with multinucleated giant cells, epithelioid cells, and lymphocytes accumulating around the lens proteins. 2)
In hypermature cataracts, liquefaction of the nucleus leads to leakage of high-molecular-weight proteins such as α-crystallin through microscopic pores in the capsule. Engorged macrophages physically obstruct the trabecular meshwork, resulting in secondary open-angle glaucoma.
It is reported that more than 50% of LIU cases are complicated by secondary glaucoma (phacoanaphylactic glaucoma). 3) The 5th edition of the EGS Glaucoma Guidelines defines this as an independent disease entity. 3)
Preoperative evaluation of the capsule using ultrasound biomicroscopy (UBM) contributes to improved diagnostic accuracy.
Lopez-Zuniga et al. (2025) reported a case of LIU in a 76-year-old male where UBM confirmed an intact capsule, leading to a diagnosis of phacolytic type. This allowed appropriate planning of the surgical approach. 1)
UBM enables preoperative assessment of capsular rupture and aids in the choice between extracapsular cataract extraction and phacoemulsification. Future improvements in noninvasive preoperative diagnostic accuracy are expected through combination with OCT.
Conventionally, LIU was often considered an anterior segment disease, but inflammatory spread to the vitreous cavity (retrolental opacity) has come to be recognized.
Lopez-Zuniga et al. (2025) showed that performing anterior vitrectomy simultaneously with PEA + IOL insertion can achieve good postoperative visual acuity (20/25 at 2 months postoperatively) even in cases with retrolental opacity. 1)
In developing countries and rural areas, neglected cataracts lead to an increase in hypermature cataracts, and the incidence of LIU remains high. 2)
Bievel-Radulescu et al. (2021) reported the case of an 83-year-old farmer with limited healthcare access, highlighting the challenges of late-stage cataract management in rural areas. 2)
Cataract outreach programs and mobile ophthalmic surgical teams are gaining attention as preventive interventions.
