Lens-Induced Glaucoma

Etiology

Congenital Ectopia Lentis (EL) can result in aqueous flow obstruction. Various forms include the following:

• Marfan syndrome - Bilateral supero-temporal subluxation of the lens with occasional acute dislocation and PBG in early childhood[2]
• Homocystinuria - Bilateral inferonasal lenticular subluxation with acute anterior chamber dislocation and PBG are common.[3]
• Weill-Marchesani syndrome - Microspherophakia, ciliary body hypoplasia, PBG, and inverse glaucoma are associated.
• Others: Ehler-Danlos syndrome, sulfite oxidase deficiency, hyperlysinemia, aniridia, Alport syndrome, Axenfeld-Rieger syndrome, and Peter anomaly type 3

Acquired includes the following:

• Trauma - Can cause anterior dislocation of lens and PBG. Traumatic rupture of the lens causes immediate LPIG or a delayed PAG.
• Post-surgery - Retained loose lenticular matter can precipitate an acute attack of LPIG or a chronic PAG.
• Intumescent cataract - Can cause PMG.
• HMSC - Micro-ruptures in the lens capsule cause PLG.

Epidemiology

The epidemiology varies across developed and developing countries. The congenital varieties form a greater proportion in the developed countries with easy access to healthcare. The estimated prevalence of congenital ectopia lentis is 6.4 per 100,000 population.[4] 

In developing countries with more limited resources, acquired LIG from advanced senile cataracts is the more prevalent subtype. The incidence of LIG is up to 2.4% at the time of the presentation of senile cataracts with a female preponderance.[1]

Pathophysiology

PLG: Flocks coined the term - Phacolytic glaucoma (see Image. Phacolytic Glaucoma).[5] Epstein described the role of high-molecular-weight lens protein (HMW-LP) in the pathogenesis of PLG.[6][7] Microdefects in the cataractous lens capsule lead to a progressive leak of the soluble lens proteins into the aqueous humor. The macrophages phagocytose these proteins and block the trabecular meshwork (TM), causing acute open-angle glaucoma.[6] The recent theory states that HMW-LP directly obstructs the TM to impede the aqueous outflow and precipitates PLG. The increase in the content of HMW-LP in the human lens with increasing age supports this theory.

LPIG: Lens-particle-induced glaucoma was previously mislabeled as 'phacotoxic uveitis.' Lens particles are released after extra-capsular cataract extraction (ECCE) or a traumatic lens capsule rupture. The lens particles deposit directly into the TM, obstructing the aqueous outflow and leading to open-angle glaucoma (see Image. Lens Particle Glaucoma). There is minimal-to-nil inflammation in LPIG.

PAG: Verhoeff and Lemoine described this entity as 'endophthalmitis phacoanaphylactica.[8] The release of lens particles is similar to LPIG (see Image. Phacoanaphylactic Glaucoma). There is a sensitization period of 1 to 14 days between the release and the onset of glaucoma.[9] The inflammation of TM is mediated by type III hypersensitivity - Arthus type reaction mediated by IgG and the complement system.[10]

PBG: The mechanism of classic pupillary block glaucoma is obstruction of aqueous flow in the mid-dilated pupil. An anteriorly positioned lens may worsen this condition. The ectopia lentis with an anteriorly dislocated lens also blocks the aqueous flow similarly. 

PMG: Phacomorphic glaucoma is precipitated by a sudden increase in the volume of the cataractous lens (see Image. Phacomorphic Glaucoma). The presence of an intumescent cataractous lens leads to pupillary block. Acute angle-closure with a shallow anterior chamber, with an open angle in the contralateral eye, suggests PMG. 

Histopathology

For the acute inflammatory entities - PLG and PAG, a cytopathology examination of the aqueous humor suggests 2 distinct inflammatory patterns. PLG shows a chronic inflammatory reaction and macrophages with engulfed lens proteins.[11] PAG has a granulomatous reaction zone with polymorphonuclear leukocytes, giant cells, epithelioid cells, and a cuff of lymphocytes and plasma cells.[12] 

History and Physical

The common ocular complaints in patients of LIG are:

• Redness of the eye- sudden onset
• Unilateral eye pain - sudden onset, may be accompanied by headache, nausea, and vomiting
• Diminution of vision - gradually progressive in cases of cataracts
• Colored halos, photophobia, and epiphora 

A detailed history of the presenting symptoms' onset, duration, and progression is essential. The clinician must note any history of similar episodes or ocular surgery. Any clinical history suggestive of a contraindication to systemic steroid use like osteoporosis, peptic ulcer disease, psychiatric illness, or tuberculosis should be elicited.

Evaluation

The evaluation of lens-induced glaucoma includes:

• Measure the best-corrected visual acuity and any improvement with the pinhole. For EL cases, cycloplegic refraction may be performed. 
• Facial symmetry and head posture
• Binocular alignment: The eyes with advanced cataracts and poor vision can have sensory exotropia. A comitant squint since childhood suggests a poor visual prognosis in unilateral EL cases. 

Clinical Examination

• Ocular adnexa: Possible swelling and redness of the eyelids
• Conjunctiva: Congestion and chemosis 
• Sclera: Dilated episcleral vessels
• Cornea: The raised IOP causes stromal edema, sub-epithelial bullae, and Descemet membrane folds. PAG and PLG cases show fresh keratitic precipitates on the posterior surface of the cornea. Lens proteins deposit on the posterior surface of the cornea in LPIG. 
• Anterior chamber (AC): AC depth decreases in PMG and PBG. The aqueous humor shows lens particles in LPIG. PAG and PLG show AC reactions due to inflammatory cells and AC flare due to leakage of inflammatory proteins. PLG shows hyper-refringent particles composed of calcium oxalate or cholesterol crystals.[13]
• Iris: PBG and PMG show anterior bowing of the iris. Prolonged inflammation in PAG or PLG may present with posterior synechiae and peripheral anterior synechiae (PAS). Inflammatory pseudo-hypopyon is rarely seen in PAG.
• Pupil: The cases with a prolonged rise of IOP have a vertically oval pupil due to ischemia of the sphincter pupillae muscle. PBG has a classical mid-dilated pupil. Chronic PAG and PLG cases can exhibit a festooned pupil. A brisk consensual light reflex in the contralateral eye suggests an excellent visual prognosis. 
• Lens: PMG shows an intumescent mature senile cataract (MSC). In LPIG, a rupture of the lens capsule with a cataractous lens may be visible. PLG shows MSC or HMSC. PAG can have a ruptured lens capsule or an anterior capsulorhexis with residual lens matter. PBG due to EL demonstrates an anteriorly positioned lens. 
• Posterior segment: Cases of total cataracts obstruct the view of the fundus. 

Investigations

• Applanation tonometry (AT): Goldmann AT is the gold standard for IOP measurement.
• Gonioscopy: Angle examination is mandatory in cases with a clear cornea. PMG shows a closed or an occludable angle in the involved eye, with a narrow or open-angle in the contralateral eye depending on the stage of cataract in that eye. An occludable angle in the contralateral eye suggests a PBG mechanism. LPIG shows an open angle with lens particle deposition. Chronic PLG and PAG may have synechial angle closure with PAS formation. EL often has a 'volcano configuration' of the iris, with the pupil forming the central crater.
• Ocular ultrasonography provides an image of the posterior segment in cases with no view of the fundus. 
• Anterior segment ocular coherence tomography (AS-OCT): A reduced AC depth and angle opening distance, increased lens vault, and axial length correlate with PMG.[14]
• Aqueous humor cytology is rarely required to help elucidate the pathology in uveitis of unknown etiology. It helps differentiate PAG or PLG from infective conditions.

Treatment / Management

The primary goal is adequate intraocular pressure (IOP) control. The definitive management is the removal of inciting lenticular matter. 

IOP Management

• Laser peripheral iridotomy (LPI): For PBG and PMG, it may relieve any component of the pupillary block but may be insufficient to control the IOP.
• Topical antiglaucoma medication (AGM): The first-line management includes beta-blockers, alpha-agonists, and carbonic anhydrase inhibitors. Prostaglandin analogs and miotics can be used but may increase intraocular inflammation. 
• Systemic IOP-lowering agents: Hyperosmotic agents (eg, mannitol) and carbonic anhydrase inhibitors (acetazolamide) augment the effect of topical agents. Vigilant monitoring of kidney function and serum electrolytes is essential.
• Corticosteroids: Topical and systemic corticosteroids lower the inflammation in PAG and PLG before the definitive cataract surgery.
• Pars plana vitrectomy is sometimes required before cataract surgery if there is inadequate anterior chamber space to safely perform the procedure in cases of hyper-maturity or intumescent cataracts.

Lens Extraction - ideally performed after adequate IOP control

• Cataract extraction. Per the surgeons' experience, conventional ECCE, small incision cataract surgery (SICS), or phacoemulsification techniques are employed to remove the lens.
• The traumatic lens rupture and residual lenticular matter after cataract surgery respond well to total lens aspiration in cases of LPIG and PAG. 
• Various techniques may be employed for gross lens subluxation or anterior dislocation in EL, depending on the degree of subluxation. Phacoemulsification combined with sutured capsular segments may be preferred for mild to moderate subluxation. Vitrectomy combined with pars plana lensectomy or intracapsular cataract extraction may be required for severe or posterior subluxation.
• Cataract surgery can still be performed to control inflammation and pain for patients who deny the perception of light and thus are unlikely to improve vision.

Visual Rehabilitation

• Primary implantation of a posterior chamber intraocular lens (IOL) can be performed in cases with an intact posterior capsule and adequate bag stability.
• For subluxated cataracts, devices like capsule tension rings or Cionne rings stabilize the bag and facilitate the implantation of a posterior chamber IOL.
• For ICCE and lensectomy cases, a primary or secondary scleral-fixated IOL or an anterior chamber IOL have variable success rates. In the post-surgery period, topical AGMs control the IOP.
• Gonio-synechialysis, in conjunction with cataract surgery, is a management option for PAS formation in chronic LIG.
• PLG - An immediate lens extraction alone results in a well-controlled IOP if the preceding history is less than a week. For a history of more than 2 weeks, combined cataract surgery with trabeculectomy shows better IOP control.[15]
• PMG - Cataract surgery alone is useful for IOP control and visual rehabilitation for patients presenting within 4 weeks. A combined surgery - lens extraction and trabeculectomy, is planned for chronic PMG.[16]
• For painful blind eyes, cataract surgery or cyclodiode laser treatment may be considered to lower the IOP.
(B2)

Differential Diagnosis

Acute angle-closure glaucoma (ACG): This entity can be confused with PMG or PLG. Eliciting a positive family history of glaucoma and a history of past similar episodes helps differentiate them. Gonioscopy of the contralateral eye helps distinguish the exact mechanism.

Ciliary block glaucoma (CBG): Malignant glaucoma or aqueous misdirection syndrome occurs due to anterior rotation of the ciliary body and accumulation of aqueous behind the anterior hyaloid. PBG is a commonly confused entity. Laser peripheral iridotomy (LPI) is diagnostic as it provides relief of the PBG attack, while no lowering of the IOP occurs in CBG. 

Supra-choroidal hemorrhage: It can mimic PBG with a flat AC and raised IOP. A detailed fundus evaluation shows a classic dark red elevation, or, in cases of poor fundus view, a B-scan ultrasound can be performed to aid in the diagnosis. 

Choroidal effusion: This condition classically presents with a low IOP. If the effusion involves a ciliary body and secondary cyclodialysis, it can present with raised IOP and a flat AC, mimicking PBG.

Post-traumatic endophthalmitis: The presence of a hypopyon, elevated IOP, corneal edema, or AC flare with a ruptured lens can mimic or coexist with PAG. A microbiological evaluation of the anterior chamber or vitreous tap helps exclude endophthalmitis.

Prognosis

An early presentation and prompt management may allow a good visual prognosis. Early lens extraction under adequate IOP control is the cornerstone of management. Delayed and chronic presentations have a poorer prognosis. The development of PAS is a poor prognostic indicator and requires regular IOP monitoring with medical and/or surgical management.

The combined cataract extraction with trabeculectomy has good IOP control in the immediate post-surgical period. However, the trabeculectomy failure rates of combined surgery are high in the long term.

Complications

The complications that can manifest with lens-induced glaucoma are as follows:

• Persistent inflammation
• Pigment and/or proteinaceous deposits on the IOL 
• PAS formation - synechial ACG
• Persistent elevation of IOP with failure of glaucoma filtration surgery
• Poor gain of vision
• Glaucomatous optic atrophy
• Endophthalmitis
• Expulsive choroidal hemorrhage
• Loss of vision
• Painful atrophic bulbi
• Phthisis bulbi