What are the new types of ophthalmic drugs for treating glaucoma, especially in patients with a history of trabeculectomy and complications like cystic blebs?

New Ophthalmic Drug Classes for Glaucoma

The newest classes of ophthalmic drugs for glaucoma include Rho kinase (ROCK) inhibitors (netarsudil) and combination therapies pairing ROCK inhibitors with prostaglandin analogues (netarsudil/latanoprost), which represent the first novel mechanism of action since prostaglandin analogues emerged in the mid-1990s. 1, 2

Novel Drug Classes

Rho Kinase (ROCK) Inhibitors

• Netarsudil 0.02% is the first FDA-approved ROCK inhibitor for glaucoma, working through a novel mechanism by increasing trabecular meshwork outflow and reducing episcleral venous pressure 1
• This represents the first new drug class with a distinct mechanism of action in over two decades 2

Fixed-Dose Combination Therapy

• Netarsudil/latanoprost 0.02%/0.005% (ROCKLATAN) combines ROCK inhibition with prostaglandin analogue therapy in a single formulation 1
• Clinical trials demonstrate this combination provides 1-3 mmHg greater IOP reduction compared to either netarsudil or latanoprost monotherapy throughout 12 months of treatment 1
• The combination is dosed once daily in the evening 1

Established First-Line Therapy

Prostaglandin Analogues (PGAs)

• PGAs remain the most effective initial medical treatment for reducing IOP in both open-angle glaucoma and primary angle-closure glaucoma 3
• Bimatoprost 0.03% is a widely-used PGA that reduces IOP by increasing uveoscleral outflow, with maximum effect reached within 8-12 hours after administration 4
• PGAs can be combined with other drug classes (such as 0.5% timolol) to achieve better IOP reduction 3

Important Caveats with PGAs

• PGAs cause more conjunctival hyperemia (15-45% of patients) than other monotherapy options but have a favorable systemic safety profile 3, 4
• Permanent iris pigmentation can occur with continued use, though periorbital pigmentation and eyelash changes may be reversible after discontinuation 4
• Eyelash changes (increased length, thickness, number) occur gradually and are usually reversible 4

Adjunctive Therapy Options

Alpha-2 Adrenergic Agonists

• Brimonidine is effective as adjunctive therapy and for preventing IOP spikes after laser trabeculoplasty 3
• Can be used perioperatively to prevent temporary IOP elevations, particularly in severe disease 3

Carbonic Anhydrase Inhibitors

• Topical formulations (dorzolamide, brinzolamide) provide additional 15-20% IOP reduction when added to other agents 5
• Oral/IV formulations reserved for acute IOP crises or refractory cases 5

Special Considerations for Post-Trabeculectomy Patients

Managing Cystic Blebs

• Fornix-based conjunctival flaps are strongly preferred over limbus-based flaps when performing trabeculectomy, as they result in diffuse blebs (29% cystic rate) rather than cystic blebs (90% cystic rate with limbus-based flaps) 6, 7
• Cystic blebs carry significantly higher risks of late-onset infection, bleb leaks, and hypotony 3, 7
• In patients with existing cystic blebs from prior surgery, medical therapy should be optimized before considering revision surgery 3

Bleb Management Adjuncts

• 5-fluorouracil needling has proven effective for reviving failing filtering blebs 3
• Antifibrotic agents (mitomycin-C, 5-fluorouracil) improve IOP control but increase risks of hypotony, late bleb leak, and infection that must be weighed against benefits 3

Treatment Algorithm

For patients with history of trabeculectomy and cystic blebs:

1. Maximize medical therapy first with PGA monotherapy (if not already on maximum tolerated therapy) 3
2. Add adjunctive agents if monotherapy insufficient: consider netarsudil/latanoprost combination or add topical carbonic anhydrase inhibitor or brimonidine 3, 1
3. Avoid multiple daily dosing of PGAs as this decreases efficacy 4
4. Monitor for bleb complications including late leaks, infection, and hypotony at each visit 3
5. Consider 5-fluorouracil needling if bleb failure occurs before proceeding to repeat surgery 3

Critical Pitfalls to Avoid

• Never administer PGAs more than once daily as increased frequency reduces IOP-lowering effectiveness 4
• Do not use topical NSAIDs after trabeculectomy as they provide no advantage over topical steroids for postoperative IOP control 3
• Avoid limbus-based conjunctival flaps in any future trabeculectomy procedures due to 90% cystic bleb rate and 20% infection risk 7
• Monitor for macular edema when using bimatoprost in aphakic or pseudophakic patients with torn posterior capsule 4
• Remove contact lenses before instilling bimatoprost due to benzalkonium chloride absorption and discoloration risk 4

Evidence Limitations

• No systematic review evidence supports neuroprotection, nutritional supplementation, or alternative therapies for glaucoma management 3
• Uncertainty remains regarding MIGS devices and their comparative effectiveness versus traditional surgery 3
• No high-quality evidence exists for managing encapsulated blebs or late bleb leaks specifically 3