Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
add-on or switch to another topical ophthalmic
Treatment recommended for SOME patients in selected patient group
If a prostaglandin analog monotherapy fails to reduce intraocular pressure (IOP), or causes intolerable adverse effects, the patient may be switched to an alternative topical ophthalmic agent. Options include beta-blockers, alpha-2 adrenergic agonists, carbonic anhydrase inhibitors, latanoprostene bunod, rho kinase inhibitors, and cholinergic agonists, alone or in combination.
Beta-blockers (e.g., timolol, carteolol, betaxolol) are a first-line alternative/add-on option. They 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) are another first-line alternative/add-on option. They decrease activity of the carbonic anhydrase enzyme in the ciliary body, thereby lowering aqueous humor production. Topical carbonic anhydrase inhibitors are associated with significantly fewer adverse effects compared with oral administration and lower IOP by 15% to 20%.[8]
Alpha-2 adrenergic agonists (e.g., apraclonidine, brimonidine) are a second-line alternative/add-on option. They 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. Alpha-2 adrenergic agonists 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 another second-line alternative. It 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 latanoprostene bunod had greater IOP-lowering efficacy than timolol at 1 month, and that this effect was maintained for 12 months.[62] The safety profile of latanoprostene bunod is comparable to 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]
[ 
]
A subsequent systematic review and meta-analysis concluded that netarsudil is clinically noninferior to beta-blockers.[65]
Cholinergic agonists (e.g., pilocarpine) are a third-line alternative/add-on option. Cholinergic agonists 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.
Topical ophthalmic agents from different classes are often combined when treatment response is partial. A fixed-dose combination eye drop that includes two or more active drugs from different classes in a single dosage is more convenient for the patient and may improve adherence. Various therapeutic combinations are available.[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 side effects, medication adherence, and past medical history).
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) can cause systemic adverse effects and may prove incompatible with patients who have severe cardiovascular or pulmonary disease.
Treatment is generally lifelong, unless surgical intervention is undertaken or a medication change is required.
Primary options
Beta-blocker
timolol ophthalmic: (0.25% or 0.5%) 1 drop into the affected eye(s) twice daily; (0.25% or 0.5% gel) 1 drop into the affected eye(s) once daily
OR
Beta-blocker
carteolol ophthalmic: (1%) 1 drop into the affected eye(s) twice daily
OR
Beta-blocker
betaxolol ophthalmic: (0.25% or 0.5%) 1-2 drops into the affected eye(s) twice daily
OR
Carbonic anhydrase inhibitor
brinzolamide ophthalmic: (1%) 1 drop into the affected eye(s) three times daily
OR
Carbonic anhydrase inhibitor
dorzolamide ophthalmic: (2%) 1 drop into the affected eye(s) three times daily
Secondary options
Alpha-2 adrenergic agonist
apraclonidine ophthalmic: (0.5%) 1-2 drops into the affected eye(s) three times daily
OR
Alpha-2 adrenergic agonist
brimonidine ophthalmic: (0.1% or 0.15%) 1 drop into the affected eye(s) three times daily
OR
Prostaglandin analog
latanoprostene bunod ophthalmic: (0.024%) 1 drop into the affected eye(s) once daily in the evening
OR
Rho kinase inhibitor
netarsudil ophthalmic: (0.02%) 1 drop into the affected eye(s) once daily in the evening
Tertiary options
Cholinergic agonist
pilocarpine ophthalmic: (1%, 2%, 4%) 1 drop into the affected eye(s) up to four times daily
surgery
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 is less invasive because it does not involve a full-thickness breach of the eye wall, but it has a higher degree of surgical difficulty compared with trabeculectomy. Techniques include deep sclerectomy, viscocanalostomy, and canaloplasty. Although nonpenetrating procedures may be less effective at lowering intraocular pressure (IOP) than trabeculectomy, they have a preferable safety profile.[81] The type of surgery chosen should be tailored to the patient's needs.
Microinvasive glaucoma surgery involves minimal trauma to ocular tissues. It typically refers to the use of implants, devices, or techniques to reduce IOP. Examples include ab-interno trabeculectomy and trabecular microbypass stents. In patients with newly diagnosed advanced glaucoma, primary treatment with trabeculectomy may offer superior intraocular pressure control compared with eye drops.[82]
Very advanced glaucoma with poor vision prognosis may benefit from cyclodestructive procedures. Such procedures damage the ciliary body and decrease aqueous humor production.
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 by 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]
[ ]
[ ]
Surgeries can cause some loss of vision and make the eye more susceptible to infection and inflammation.
[ ]
Infections are treated aggressively with ophthalmic and intraocular antibiotics. Inflammation will subside as infection subsides. Mild loss of vision may resolve in time or be permanent.
Antifibrotic agents may be considered to reduce postoperative scarring in patients undergoing trabeculectomy, but they may increase risk for bleb leak, infection, and hypotony.[8]
surgery
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.
Nonpenetrating glaucoma surgery is less invasive because it does not involve a full-thickness breach of the eye wall, but it has a higher degree of surgical difficulty compared with trabeculectomy. Techniques include deep sclerectomy, viscocanalostomy, and canaloplasty. Although nonpenetrating procedures may be less effective at lowering intraocular pressure (IOP) than trabeculectomy, they have a preferable safety profile.[81] The type of surgery chosen should be tailored to the patient's needs.
Microinvasive glaucoma surgery involves minimal trauma to ocular tissues. It typically refers to the use of implants, devices, or techniques to reduce IOP. Examples include ab-interno trabeculectomy and trabecular microbypass stents. In patients with newly diagnosed advanced glaucoma, primary treatment with trabeculectomy may offer superior intraocular pressure control compared with eye drops.[82]
Very advanced glaucoma with poor vision prognosis may benefit from cyclodestructive procedures. Such procedures damage the ciliary body and decrease aqueous humor production.
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 by direct ablation of the meshwork.[83] One Cochrane review found low-quality evidence that combined cataract and glaucoma surgery may result in better control of intraocular pressure compared with 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]
[ ]
[ ]
Surgeries can cause some loss of vision and make the eye more susceptible to infection and inflammation.
[ ]
Infections are treated aggressively with ophthalmic and intraocular antibiotics. Inflammation will subside as infection subsides. Mild loss of vision may resolve in time or be permanent.
Antifibrotic agents may be considered to reduce postoperative scarring in patients undergoing trabeculectomy, but they may increase risk for bleb leak, infection, and hypotony.[8]
Choose a patient group to see our recommendations
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
Use of this content is subject to our disclaimer