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Glaucoma Lens Particle Background Lens-particle glaucoma, a subclassification of lens-induced glaucoma,1,2,3,4,5 is a type of secondary open-angle glaucoma involving intraocular

retention of fragmented lens debris. Following surgery or injury, lens material may be sequestered within the capsular bag or dislocated into other areas of either the posterior eye or the anterior eye. Characteristically, large lens pieces spontaneously fragment further into small (sometimes invisible) particles that eventually migrate into the anterior chamber and obstruct aqueous outflow.6 Lens-particle glaucoma is not associated with decentration or dislocation of an intact lens. Pathophysiology The mechanism involves the following 4 processes: (1) presence of a nonintact lens capsule, usually violated during trauma or intraocular surgery; (2) dislocation of lens fragments into the anterior or posterior segment, with subsequent release of lens particles into the anterior chamber; (3) obstruction of trabecular meshwork by lens debris6 and inflammatory components7 ; and (4) reduction of the outflow facility of an open anterior chamber angle, resulting in elevation of intraocular pressure (IOP). Frequency United States The incidence of lens-particle glaucoma has not been specifically reported. The frequency of penetrating eye injury in the United States has been estimated at 3.1 per 100,000 person-years,8 with a predominance of young males. Mortality/Morbidity Mortality is not associated with this condition. Morbidity is rare. Race No known racial predilection exists. Sex No known gender predilection exists for lens-particle glaucoma. However, penetrating eye trauma, a risk factor for lens-particle glaucoma, has been reported to occur more commonly in young adult males.8 Alcohol abuse is a significant comorbidity in this population. Age All ages are affected, ranging from infancy (especially when involving congenital cataract surgery) to late adulthood. Penetrating eye injuries occur most frequently in young adults. However, lens-particle glaucoma probably occurs most commonly in elderly persons as a complication of cataract surgery. Clinical History

Patients are often asymptomatic.

Depending on the severity of IOP elevation and associated intraocular inflammation, symptoms of monocular eye pain, redness, and/or blurred vision may be present. Although spontaneous rupture of the lens capsule has been described, a recent or remote history of trauma or intraocular surgery2,9 particularly cataract extraction, typically is present. The onset of lens-particle glaucoma has been reported to occur many years after cataract surgery10,11
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Lens-particle glaucoma is commonly encountered in cases of phacoemulsification that were complicated by a posteriorly dislocated lens nucleus. Obstruction of the trabecular meshwork by lens material may have a role in the mechanism of an early postoperative IOP spike after uncomplicated phacoemulsification.

Lens-particle glaucoma also may cause elevated IOP after laser capsulotomy12 Obtain any history of YAG laser procedures in all pseudophakic patients under evaluation for glaucoma.

Dislocation of a posterior intraocular lens has been reported to cause late onset lensparticle glaucoma13

Treatment Medical Care


The elevated IOP of lens-particle glaucoma often responds to medical management. Topical beta-adrenergic antagonists are typical first-line agents. Topical alpha-adrenergic agonists and carbonic anhydrase inhibitors are considered adjunctive agents. Be especially cautious when choosing a topical carbonic anhydrase inhibitor in cases involving compromised corneal endothelial function; irreversible corneal decompensation has been described in such scenarios.

Prostaglandin analogues have not been tested, but exercise caution when using such agents in the postoperative period. Theoretical risks of increased inflammation and/or cystoid macular edema exist.

Likewise, miotic agents may exacerbate anterior segment inflammation. In emergency management of severe acute lens-particle glaucoma, hyperosmotic agents have a useful role in controlling IOP. In managing this condition, treat the associated uveitis. Initial therapy typically involves a topical corticosteroid agent in conjunction with a topical cycloplegic agent.

Surgical Care Consider surgical intervention in cases that involve large amounts of unabsorbed lens material, posteriorly dislocated lens or nuclear fragment, or uncontrolled IOP with conventional medical

management. Nucleus fragments in the anterior chamber should be removed surgically because of the risk of corneal decompensation. In contrast, cortical fragments in the anterior chamber often can be observed for breakdown and resorption, with appropriate medical management.

Removal of cortical debris from the posterior chamber usually requires irrigation and aspiration of lens material adherent to the lens capsule or ciliary sulcus.
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Intraocular lens repositioning or exchange may be necessary. Capsulectomy with anterior vitrectomy also may be indicated if the posterior capsule and/or zonules are not intact. Anterior chamber washout, achieved by irrigation and aspiration of balanced salt solution, is recommended to maximally remove the lens debris from the angle.

Management of posterior dislocation of lens material varies depending on the anticipated risk of complications. Prompt vitreoretinal surgery is usually indicated. However, a total lens dislocation with an intact capsule may not require immediate surgical intervention because the risks of glaucomatous, inflammatory, or retinal complications are lower in this setting.

Similarly, very small intravitreal nuclear fragments may be tolerated without specific intervention. Both the lens-particleinduced glaucoma and the inflammatory response appear to be proportionate to the size of the fragment.

Large nuclear fragments are tolerated poorly in the posterior segment, even over short periods. Because of significant risks of further complications, the primary cataract surgeon should not attempt to retrieve intravitreal lens fragments from an anterior approach.17,18,19,20 Immediate consultation with a vitreoretinal surgeon is recommended.

Pars plana vitrectomy (with removal of lens fragments by aspiration with a fragmatome in the midanterior vitreous cavity) has become the indicated management for large intravitreal nucleus fragments.19,20,21,22,23,24,25 Immediate pars plana vitrectomy at the same sitting for dislocated lens fragments during cataract surgery has been described.26,27,5

Posterior vitreolensectomy has been associated with postoperative improvement or resolution of lens-particle glaucoma. Good visual outcomes have been reported.20,21,22,24,25

Consultations

Immediately obtain a vitreoretinal consultation in the event of posterior lens dislocation as a complication of cataract surgery. Several studies have indicated that early vitrectomy (within 3 wk postoperatively) is associated with more favorable visual results.28,26,27

Also, consider a retinal consultation to assist in differentiating postoperative phacoantigenic uveitis from endophthalmitis or sympathetic ophthalmia.

Medication

The goal of therapy is IOP reduction. Medications often can be used short term and then discontinued. IOP should be monitored after stopping medications, and therapy should be reinstituted when necessary. Bimatoprost (Lumigan), travoprost (Travatan), latanoprost (Xalatan), and unoprostone (Rescula) are ophthalmic prostaglandin analogs approved in the United States. Bimatoprost is a prostamide analog with ocular hypotensive activity. It mimics the IOP-lowering activity of prostamides via the prostamide pathway. Travoprost and unoprostone are prostaglandin F2-alpha (ie, dinoprost) analogs similar to latanoprost. They are selective FP prostanoid receptor agonists believed to reduce IOP by increasing uveoscleral outflow. They are indicated for the lowering of IOP in patients with open-angle glaucoma or ocular hypertension who are intolerant of other IOP-lowering medications or insufficiently responsive (failed to achieve target IOP determined after multiple measurements over time) to another IOP-lowering medication. Bimatoprost and travoprost are each administered once daily at bedtime (ie, 1 gtt in affected eye[s] hs); whereas, unoprostone must be administered twice daily. They have not been studied in pediatric patients. The role of prostaglandin analogs in the management of lens-particle glaucoma has not been specifically reported. These medications are contraindicated if hypersensitivity has been documented. No drug interactions have been reported. All are classified as pregnancy category C (ie, fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus). All ocular prostaglandin analogs demonstrate the unusual adverse effect of permanent increase in pigment of the iris (ie, increases brown pigment) and eyelid, and they may increase eyelash growth. Bacterial keratitis may occur. Use is cautioned in uveitis or macular edema. They should not be used if inflammation is present. Beta-blockers Topical beta-adrenergic receptor antagonists decrease aqueous humor production by the ciliary body. Adverse effects are due to systemic absorption of the drug, resulting in decreased cardiac output and bronchoconstriction. In susceptible patients, this may cause bronchospasm, bradycardia, heart block, or hypotension. Monitor the patient's pulse rate and blood pressure. Patients may be instructed to perform punctal occlusion after administering the drops. Depression or anxiety may be experienced in some patients, and sexual dysfunction may be initiated or exacerbated. Levobunolol (Betagan, AKBeta) 0.25%, 0.5% Nonselective beta-adrenergic blocking agent that lowers IOP by reducing aqueous humor production and possibly increases outflow of aqueous humor. Dosing Adult 1 gtt bid Pediatric

Not established Interactions May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects) Contraindications Documented hypersensitivity; COPD; CHF; asthma; cardiac conduction defects; breastfeeding Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Beta-blockade may potentiate muscle weakness that is consistent with certain myasthenic symptoms (eg, diplopia, ptosis, generalized weakness); product may have sulfites, which may cause allergic-type reactions in certain susceptible persons Betaxolol (Betoptic) 0.25%, 0.5% Selectively blocks beta1-adrenergic receptors with little or no effect on beta2-receptors. Reduces IOP by reducing production of aqueous humor. Dosing Adult 1 gtt bid Pediatric Not established Interactions May have additive systemic effects if patient is already on systemic beta-blockers Contraindications Documented hypersensitivity; CHF; cardiac conduction defects (possibly less effect on airways due to beta1 selectivity); breastfeeding Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Beta-blockade may potentiate muscle weakness consistent with myasthenic symptoms; product may have sulfites, which may cause hypersensitivity reactions in susceptible persons Carteolol HCl (Ocupress) 1% Blocks beta1- and beta2-receptors and has mild intrinsic sympathomimetic effects. Dosing

Adult 1 gtt bid Pediatric Not established Interactions May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects) Contraindications Documented hypersensitivity; CHF; asthma; cardiac conduction defects; breastfeeding Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Product may have sulfites, which may cause allergic-type reactions in certain susceptible persons Timolol maleate (Timoptic, Timoptic XE) 0.25%, 0.5% May reduce elevated and normal IOP, with or without glaucoma, by reducing production of aqueous humor or by outflow. Dosing Adult 1 gtt bid Pediatric Not established Interactions May cause bradycardia and asystole when used in combination with systemic beta-blockers (may cause additive effects) Contraindications Documented hypersensitivity; bronchial asthma; sinus bradycardia; second- and third-degree AV block; severe COPD; overt cardiac failure; cardiogenic shock Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Product may have sulfites, which may cause allergic-type reactions in susceptible patients; may exacerbate or precipitate heart block, asthma, COPD, and mental changes (especially in elderly persons)

Adrenergic agonists Topical adrenergic agonists (sympathomimetics) decrease aqueous production and reduce resistance to aqueous outflow. Adverse effects include dry mouth and allergenicity. Brimonidine (Alphagan) Selective alpha2-receptor that reduces aqueous humor formation and increases uveoscleral outflow. Dosing Adult 1 gtt bid (bid dosing may be as effective as tid) Pediatric Not established Interactions Coadministration with topical beta-blockers may further decrease IOP; tricyclic antidepressants may decrease effects of brimonidine; CNS depressants, such as barbiturates, opiates, and sedatives, may potentiate effects of brimonidine Contraindications Documented hypersensitivity; patients receiving MAOIs Precautions Pregnancy B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals Precautions May exacerbate or precipitate ocular irritation, topical sensitivity, vasovagal attack, and optic nerve ischemia in patients with advanced glaucomatous optic neuropathy Apraclonidine (Iopidine) 0.5%, 1% Reduces elevated, as well as normal, IOP whether or not accompanied by glaucoma. Apraclonidine is a relatively selective alpha-adrenergic agonist that does not have significant local anesthetic activity. Has minimal cardiovascular effects. Dosing Adult 1 gtt tid Pediatric Not established Interactions Monitor pulse and BP frequently when giving cardiovascular drugs; not for use concurrently with MAOIs Contraindications Documented hypersensitivity; patients on MAOIs or have taken them in the past 14 d Precautions

Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions May exacerbate or precipitate ocular irritation, topical sensitivity, vasovagal attack, and optic nerve ischemia in patients with advanced glaucomatous optic neuropathy Carbonic anhydrase inhibitors Reduce secretion of aqueous humor by inhibiting carbonic anhydrase (CA) in the ciliary body. These drugs are less effective, and their duration of action is shorter than many other classes of drugs. Adverse effects are relatively rare but include superficial punctate keratitis, acidosis, paresthesias, nausea, depression, and lassitude. Corneal decompensation has been reported when this class of drugs is used in patients with corneal endothelial dysfunction. Dorzolamide HCl (Trusopt) 2% Used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one ophthalmic drug is being used, administer the drugs at least 10 min apart. Reversibly inhibits CA, reducing hydrogen ion secretion at renal tubule, and increases renal excretion of sodium, potassium bicarbonate, and water to decrease production of aqueous humor. Dosing Adult 1 gtt tid Pediatric Not established Interactions Coadministration with high-dose salicylate therapy may increase toxicity; may have additive systemic effects if patient is already on oral CA inhibitors Contraindications Documented hypersensitivity Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Local ocular adverse effects, primarily conjunctivitis and lid reactions, may occur with long-term administration of dorzolamide (discontinue therapy and evaluate patient before restarting therapy) Brinzolamide (Azopt) 1%

Catalyzes reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. May use concomitantly with other topical ophthalmic drug products to lower IOP. If more than one topical ophthalmic drug is being used, administer drugs at least 10 min apart. Dosing Adult 1 gtt tid Pediatric Not established Interactions May have additive systemic effects if patient is already on oral CA inhibitors Contraindications Documented hypersensitivity Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Local ocular adverse effects, primarily conjunctivitis and lid reactions, may occur with long-term administration (discontinue therapy and evaluate patient before restarting therapy) Dorzolamide HCl/timolol maleate (Cosopt) Combination drug of carbonic anhydrase inhibitor and beta-blocker. Dosing Adult 1 gtt bid Pediatric Not established Interactions Coadministration with high-dose salicylate therapy may increase toxicity; may have additive systemic effects if patient is already on oral CA inhibitors Contraindications Documented hypersensitivity; COPD; CHF; asthma; cardiac conduction defects; breastfeeding Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions

Local ocular adverse effects, primarily conjunctivitis and lid reactions, may occur with long-term administration of dorzolamide (discontinue therapy and evaluate patient before restarting therapy); product may have sulfites, which may cause allergic-type reactions in susceptible patients Acetazolamide (Diamox) Inhibits enzyme carbonic anhydrase, reducing rate of aqueous humor formation, which, in turn, reduces IOP. Used for adjunctive treatment of chronic simple (open-angle) glaucoma and secondary glaucoma and preoperatively in acute angle-closure glaucoma when delay of surgery desired to lower IOP. Dosing Adult 125-250 mg tab PO qid or 500 mg cap PO bid; total dose not to exceed 1 g/24 h Pediatric Not established Interactions Can decrease therapeutic levels of lithium and alter excretion of drugs (eg, amphetamines, quinidine, phenobarbital, salicylates) by alkalinizing urine. Contraindications Documented hypersensitivity; hepatic disease; severe renal disease; adrenocortical insufficiency; severe pulmonary obstruction Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Patients with impaired hepatic function may go into coma; may cause substantial increase in blood glucose in some diabetic patients; severe toxicities include decrease of potassium level and blood dyscrasia such as aplastic anemia Methazolamide (Neptazane) Reduces aqueous humor formation by inhibiting enzyme CA, which results in decreased IOP. Dosing Adult 25-100 mg PO bid Pediatric Not established Interactions May increase toxicity of salicylate, digoxin; coadministration with other diuretics may induce hypokalemia; decreases effects of lithium and alters excretion of other drugs by alkalinizing urine

Contraindications Documented hypersensitivity; renal impairment Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Caution in respiratory acidosis and diabetes mellitus; impairs mental alertness and/or physical coordination; hematuria, glycosuria, polyuria, hepatic insufficiency, bone marrow suppression, thrombocytopenia/purpura, agranulocytosis, urticaria, pruritus, and rash may occur Cycloplegic agents Cholinergic antagonists commonly are used in the management of anterior intraocular inflammation, and, occasionally, they may be used in eyes with lens-particle glaucoma that have an active phacoantigenic uveitis. These topical drugs exert mydriatic and cycloplegic effects on the iris and ciliary body and reduce the permeability of the blood-aqueous barrier. Scopolamine 0.25% (I-Hyoscine) Topical antimuscarinic agent with potent mydriatic and cycloplegic action. Blocks action of acetylcholine at parasympathetic sites in the smooth muscle, producing pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia). Dosing Adult 1 gtt bid/tid/qid Pediatric Not established Interactions None reported Contraindications Documented hypersensitivity; narrow-angle glaucoma; bladder outlet obstruction; ileus/GI obstruction Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Avoid excessive systemic absorption by compressing lacrimal sac using digital pressure for 1-3 min after instillation; may produce drowsiness, blurred vision, or sensitivity to light (due to dilated pupils);

observe caution while driving or performing other tasks requiring alertness, coordination, or physical dexterity Homatropine 5% (AK-Homatropine, Isopto homatropine) Topical antimuscarinic agent with moderate cycloplegic and mydriatic effects. Homatropine is less potent than scopolamine, and the toxicity of homatropine is one fiftieth of that of atropine. Dosing Adult 1 gtt bid/tid/qid Pediatric Not established Interactions None reported Contraindications Documented hypersensitivity; narrow-angle glaucoma Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Caution in elderly persons where increased IOP may be present; toxic anticholinergic systemic adverse effects can occur but are rare when used sparingly; adverse effects are more common in children, especially infants; compressing lacrimal sac by digital pressure for 1-3 min following instillation minimizes systemic absorption Corticosteroids Corticosteroid agents commonly are used in combination with topical cycloplegics in the management of anterior uveitis. In cases of lens-particle glaucoma, the use of steroids is limited to eyes that have coexisting intraocular inflammation. Prednisolone acetate 1% (Pred Forte) Topical ophthalmic corticosteroid with approximately 3-5 times the potency of hydrocortisone. Topical corticosteroid therapy should be withdrawn by tapering the dosage. Dosing Adult 1 gtt 1-8 times/d; dosage may be adjusted according to severity of inflammation, up to 1 gtt q1h Pediatric Not established Interactions None reported

Contraindications Documented hypersensitivity; infectious diseases of the eye, particularly those associated with herpes simplex virus, zoster, fungi, and mycobacteria Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Caution in elderly persons where increased IOP may be present; toxic anticholinergic systemic adverse effects can occur but are rare when used sparingly; adverse effects are more common in children, especially infants; compressing lacrimal sac by digital pressure for 1-3 min following instillation minimizes systemic absorption Loteprednol etabonate 0.5% (Lotemax) Topical ophthalmic corticosteroid. Although less potent, loteprednol may be associated with a lower risk of steroid-induced IOP elevation when compared to prednisolone and may be preferred in patients with glaucoma who have mild-to-moderate intraocular inflammation. Topical corticosteroid therapy should be withdrawn by tapering the dosage. Dosing Adult 1 gtt 1-6 times/d; dosage may be adjusted according to severity of inflammation, up to 1 gtt q1h Pediatric Not established Interactions None reported Contraindications Documented hypersensitivity; infectious diseases of the eye, particularly those associated with herpes simplex virus, zoster, fungi, and mycobacteria Precautions Pregnancy C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus Precautions Steroid-induced elevation of IOP is a particular risk in patients with glaucoma; topical corticosteroid also associated with secondary ocular infections involving bacterial, viral, and fungal pathogens; caution in cases with erosive ocular surface disease, especially in eyes with exposure or other risk factors for corneal ulceration Complications

In addition to glaucoma, complications of retained intraocular lens particles include corneal decompensation, chronic uveitis, and cystoid macular edema.23 Pars plana vitrectomy for displaced nuclear fragments can be associated with complications21,25,22,23,24,29 of persistent glaucoma, uveitis, corneal edema, cystoid macular edema, epiretinal membrane, vitreous hemorrhage, retinal detachment, and choroidal hemorrhage.

Prognosis

Prognosis is generally good with appropriately timed medical and surgical intervention.23
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Studies have reported final visual acuities of 20/40 or better in approximately two thirds of cases of dropped nucleus requiring vitrectomy. 24,28,25,27 Elevated IOP improves significantly in response to the surgical removal of intraocular lens material. A nonsurgical approach may be equally successful in cases of small retained lens cortical fragments, if inflammation and IOP can be controlled acceptably, cellular processes in the trabecular meshwork are clearing the lens material.

Chronic open-angle glaucoma occurs in some patients following an episode of lensparticle glaucoma when lens particles have been reabsorbed. The transient presence of lens debris in the anterior chamber angle has been theorized to possibly cause long-lasting trabecular dysfunction.

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