Open-angle glaucoma

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

The American Academy of Ophthalmology supports the prompt and appropriate referral of individuals to an ophthalmologist when they present with intraocular pressure (IOP) at an abnormal level, transient or sustained loss of any part of the visual field, or a family history of glaucoma (especially if the patient is of African or Hispanic origin).[54]

The goal of treatment is to maintain quality of vision and to slow or halt neurodegeneration by lowering IOP.[55] Treatment should be initiated in patients with elevated IOP and/or visual changes and/or optic nerve changes.

Optic nerve health is tracked by assessment of the optic disk, retinal nerve fiber layer, macula, and visual field. IOP is maintained at a target level by pharmacotherapeutic and/or other interventions. If IOP is already high, and retinal damage has occurred, the aim is to lower the pressure to the target level. The target value is based on the degree of advancement of the disease.[56] A satisfactory IOP is determined by multiple factors that are specific to each patient.

Topical ophthalmic therapy

Initial treatment is usually with eye drops, and in the absence of surgical intervention, is usually lifelong. Clinical judgment and patient agreement inform the decision to start a specific medicine. If the pressure does not reduce to a satisfactory level, or if signs of progression occur, changing to a different agent or adding another eye drop may be appropriate. Use of some options may be limited by availability.

Recommended first-line options

Prostaglandin analogs (e.g., latanoprost, travoprost, bimatoprost, tafluprost) are considered superior to all other classes of pressure-lowering eye drops.[8][57] They act by increasing uveoscleral outflow and can lower IOP by 25% to 33%.[8]
Bimatoprost may reduce IOP more effectively than other prostaglandin analogs.[58][59]
If monotherapy with a prostaglandin analog fails to reduce IOP, or causes intolerable adverse reactions, the patient may be switched to an alternative topical ophthalmic agent. Where partial response is observed with good patient tolerance, combination therapy with agents from different classes may be considered.

First-line alternatives and add-on options

Beta-blockers (e.g., timolol, carteolol, betaxolol) may lower IOP by 20% to 25%.[8] Significant adverse effects include exacerbation of bronchial asthma, worsening of chronic obstructive pulmonary disease, and cardiovascular complications.[13] Management consists of stopping the offending beta-blocker and immediate treatment of systemic effects. Referral to the emergency department may be necessary. Betaxolol, a selective beta-blocker, is less likely to cause pulmonary adverse effects but lowers IOP to a lesser degree.[60]
Carbonic anhydrase inhibitors (e.g., brinzolamide, dorzolamide) act by decreasing the activity of carbonic anhydrase in the ciliary body, thereby lowering aqueous humor production. Topical carbonic anhydrase inhibitors are associated with significantly fewer adverse effects compared with oral administration. Topical carbonic anhydrase inhibitor therapy lowers IOP by 15% to 20%.[8]

Second-line alternatives and add-on options

Alpha-2 adrenergic agonists (e.g., apraclonidine, brimonidine) lower aqueous humor production. This class of drugs is known to cause local allergic reactions and should not be used in patients taking monoamine oxidase inhibitors. They lower IOP by 20% to 25%.[8] Brimonidine may cause mild hypotension; apraclonidine does not cross the blood-brain barrier, so does not cause cardiovascular adverse effects.[61] Alpha-2 adrenergic agonists are less commonly used in some countries, such as the UK.
Latanoprostene bunod is a nitric oxide-donating prostaglandin F2-alpha analog that combines the IOP-lowering effects of nitric oxide with that of a prostaglandin analog (it is rapidly metabolized to latanoprost acid). It is not, therefore, suitable for add-on therapy with other prostaglandin analogs. Latanoprostene bunod relaxes the trabecular meshwork and Schlemm’s canal to improve trabecular outflow. Pooled phase 3 data indicate that it has greater IOP-lowering efficacy than timolol at 1 month, and that this effect is maintained for 12 months.[62] The safety profile of latanoprostene bunod is comparable to that of other prostaglandin analogs.[63] It is unsuitable for patients who have not tolerated the adverse effects of other prostaglandin analogs, but it is a viable option when beta-blockers are poorly tolerated or ineffective.
Rho kinase inhibitors (e.g., netarsudil) have a novel mechanism of action, lowering IOP by modulating aqueous humor production and increasing outflow through the trabecular meshwork and Schlemm's canal. One Cochrane review concluded that netarsudil is probably inferior to latanoprost and only slightly inferior to timolol.[64] [ ] One subsequent systematic review and meta-analysis concluded that netarsudil is clinically noninferior to beta-blockers.[65]

Third-line alternatives and add-on options

Cholinergic agonists (e.g., pilocarpine) act by stimulating ciliary body contraction and opening the trabecular meshwork, so aqueous outflow is increased. IOP is decreased by 20% to 25%.[8] Cholinergic agents are rarely used due to patient intolerance and frequent dosing. When used, they are typically added to a multimedicine regimen.

Combination topical therapy

Topical ophthalmic agents from different classes are often combined when treatment response is partial. A fixed-dose combination eye drop that combines two or more active drugs from different classes in a single dose is more convenient for the patient and may improve adherence.
Various therapeutic combinations are available (e.g., prostaglandin analog plus a beta-blocker; beta-blocker plus a carbonic anhydrase inhibitor; beta-blocker plus an alpha-2 adrenergic agonist; rho kinase inhibitor plus a prostaglandin analog).[64][66][67][68][69][70][71][72] [ ]
Choice will depend on availability (proprietary combination eye drop formulation availability varies between countries) and patient factors (e.g., preference, allergies and adverse effects, medication adherence, and past medical history).

Adverse effects of topical therapy

All topical ophthalmic medications have local adverse effects; when severe, these can be managed by changing to a different drug.

Some eye drops (e.g., beta-blockers) also cause systemic adverse effects and may prove incompatible with patients who have severe cardiovascular or pulmonary disease.

Laser therapy

Laser treatments to the trabecular meshwork may be used to increase aqueous humor drainage. Several methods are available, but one Cochrane systematic review found no single laser technology to be better than another.[73]

Laser trabeculoplasty can also be used first line in primary open-angle glaucoma.[74][75][76] It is an option when eye drops fail to adequately lower IOP or are contraindicated (e.g., cardiovascular or pulmonary disease).[33]

Some laser treatments, such as argon laser trabeculoplasty, may damage the trabecular meshwork and elevate pressure transiently. Repeat argon laser therapy confers increased risk of complications compared with initial argon laser trabeculoplasty.[8] Selective laser trabeculoplasty can be repeated and is associated with less mechanical damage.[77][78][79]

Perioperative eye drops may be useful in preventing IOP spikes in the first 2-24 hours after laser trabeculoplasty.[8][80]

Ongoing topical ophthalmic therapy may be required in addition to laser treatment.[33]

Surgical intervention

When topical ophthalmic therapy and laser treatment fails, or the patient is unable to comply, incisional surgery is performed to facilitate aqueous humor outflow. Surgical options can be tailored to the severity of glaucoma and response to medical treatment. Common surgical techniques include trabeculectomy and aqueous shunt.

If the patient has cardiovascular or pulmonary disease prohibiting use of certain eye drops, and rapidly progressing disease, surgical intervention may be the first-line treatment.[8][33]

Nonpenetrating glaucoma surgery

Nonpenetrating glaucoma surgery is less invasive because it does not involve a full-thickness breach of the eye wall. Techniques include deep sclerectomy, viscocanalostomy, and canaloplasty. Nonpenetrating procedures may be less effective at lowering IOP than trabeculectomy, but with a preferable safety profile.[81] The type of surgery chosen should be tailored to the patient's needs.

Nonpenetrating procedures have a higher degree of surgical difficulty compared with trabeculectomy.

Microinvasive glaucoma surgery

Surgical procedures that involve minimal trauma to ocular tissues. Microinvasive glaucoma surgery typically refers to the use of implants, devices, or techniques to reduce IOP. Examples include ab-interno trabeculectomy and trabecular microbypass stents.

One two-arm, parallel, multicenter, pragmatic randomized controlled trial found no difference in health-related quality of life between primary trabeculectomy and primary glaucoma eye drops for patients with newly diagnosed advanced glaucoma.[82] IOP control was superior in the trabeculectomy arm. Modeling suggested that trabeculectomy may be more cost-effective over the patient’s lifetime.[82]

Cyclodestructive procedures

Very advanced glaucoma with poor vision prognosis may benefit from cyclodestructive procedures. Such procedures damage the ciliary body and decrease aqueous humor production.

Concurrent cataract and glaucoma surgery

Several procedures have been developed to treat glaucoma in patients undergoing cataract surgery. These provide direct access to Schlemm's canal by stenting across the trabecular meshwork or direct ablation of the meshwork.[83]

One Cochrane review found low-quality evidence that combined cataract and glaucoma surgery may result in better IOP control than cataract surgery alone.[84] [ ] Subsequent narrative reviews support the additive effects of cataract surgery with different glaucoma procedures for lowering IOP.[85][86]

Consideration should be given to cataract surgery with minimally invasive procedures, such as iStent or Hydrus, that can improve IOP and reduce the burden of eye drops, usually without introducing additional risk over the base procedure.[87][88][89][90] [ ] [ ]

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