Glaucoma Treatment Selection
Decision Logic, Side Effects & Taiwan Reality

1. Core principle: lifelong individualized management

Why isn't treatment just 'here's a bottle of drops'?

• Target IOP is individualized — AAO 2025 PPP suggests an initial 20-30% reduction below baseline, but actual numbers depend on severity (mild ≤18-21, moderate 15-18, severe ≤12 mmHg), progression rate, life expectancy and side-effect tolerance
• IOP is only a surrogate — what matters is whether visual field and optic-nerve structure stop deteriorating. If IOP is 'at target' but OCT/fields still worsen, treatment must be intensified
• Treatment is lifelong — glaucoma is incurable, nerve damage is irreversible, and stopping treatment may allow further progression
• Adherence is the deciding factor — studies show 1-year drop adherence is only 50-60%, which is why fixed-dose combinations, laser and durable surgical options matter so much

When the doctor says 'let's try another one' or 'let's add a bottle,' it isn't a verdict on prior treatment — it's optimization. With this mindset, the rest of the ladder makes sense.

2. First-line: SLT laser vs eye drops

① LiGHT trial: the evidence rewriting first-line

The LiGHT trial (Lancet 2019) is the key trial for SLT as first-line: 718 newly diagnosed OAG or OHT patients in the UK randomized to first-line SLT vs eye drops.

• 3-year: similar IOP control, but the SLT arm needed fewer cataract/glaucoma surgeries
• 6-year extension (JAMA Ophthalmology 2023): drop-free at every visit was 69.8% in the SLT arm vs 0% in the drops arm; less visual-field progression, fewer cataract/glaucoma surgeries, and lower overall cost

② NICE 2022 rewrites the guideline

On the strength of LiGHT, NICE 2022 NG81 lists 360° SLT as first-line for newly diagnosed OAG and OHT with IOP ≥ 24 mmHg, instead of drops. Other guidelines (AAO PPP, EGS) remain more neutral, accepting either drops or SLT as first-line.

③ Why do most Taiwanese ophthalmologists still start with drops?

This isn't a deviation from guidelines but practical individualization:

• NHI coverage differs: most drops are covered, while SLT coverage varies by hospital (some self-pay or partial pay)
• Primary-care access: drops are dispensed at any clinic; SLT is mostly available at mid-to-large hospitals
• Patient preference: many patients are wary of 'laser' and prefer trying drops first
• SLT not suitable for some: pigment dispersion syndrome, advanced glaucoma, patients unable to position
• SLT isn't universal: ~20% of patients respond poorly to SLT and ultimately still need drops

3. The five PGA drops: a complete comparison

Prostaglandin analogues (PGAs) are the most potent single-agent IOP-lowering drops, with the fewest systemic side effects and only once-daily dosing — making them the first-line drug class in most international guidelines. Taiwanese clinics see five main PGAs: latanoprost, bimatoprost, travoprost, tafluprost, and the newer dual-mechanism (uveoscleral + NO-mediated trabecular outflow) latanoprostene bunod (Vyzulta) — marketed in Taiwan but NHI coverage is restricted (often self-pay unless specific criteria are met, such as failure of other PGAs).

① Why are PGAs dosed in the evening?

IOP follows a diurnal rhythm — most people peak at night (2-6 a.m. supine), 2-6 mmHg higher than daytime. PGAs are dosed once daily and last ~24 hours, so evening dosing (1-2 hours before bed) covers the nocturnal peak. If a dose is missed, take it on noticing — don't double up the next day (PGAs paradoxically lose efficacy with overdosing, the known 'ceiling effect').

② Five-PGA comparison table

* Ranges are illustrative from international literature; individual variation is large. NHI coverage follows the latest national announcement.

③ PGA-specific side effects in detail

* Overall, bimatoprost has the highest side-effect frequency and tafluprost the lowest. PAP is significant enough to warrant the dedicated callout below.

④ Which PGA for whom?

Choose latanoprost: most adults without contraindications — many generics, lowest cost, full NHI coverage, relatively mild side effects. Start broad, escalate if needed.

Choose bimatoprost: latanoprost insufficient and stronger drop needed; patient unbothered by cosmetic side effects (lashes, PAP).

Choose tafluprost (especially preservative-free):

• Significant dry eye, ocular surface disease, contact-lens wearers
• BAK preservative allergy
• Patients heading toward glaucoma surgery — minimize conjunctival fibrosis to preserve trab/MIGS success (emphasized by ESCRS and EGS)

Avoid bimatoprost:

• Young women (cosmetic asymmetry from unilateral use)
• Pre-existing ptosis or lid laxity
• Appearance-sensitive professions

Caution with any PGA: active uveitis; CME history or recent cataract surgery; HSV keratitis history.

4. Other drug classes — side effects in detail

When PGA monotherapy is insufficient or contraindicated, other classes are added or substituted. Each has a distinctive side-effect profile, and the doctor evaluates systemic status (asthma, heart disease, diabetes, sulfa allergy, age) before prescribing. Below: a comparison table first, then per-class deep dives.

① Five-class quick-reference table

② β-blocker — the systemic-side-effect concern

The most common second-line add-on (about +5-7 mmHg on top of PGA). But topical β-blockers reach systemic circulation; their effects can rival oral β-blockers — a frequently underestimated clinic risk.

Other effects to monitor: fatigue, reduced exercise tolerance, depression (especially in elderly), sexual dysfunction. Betaxolol is β1-selective with less airway impact (relative — not absolute — contraindication for asthma) but also weaker IOP reduction.

③ α2 agonist — high allergy rate

Brimonidine is the most common α2 in Taiwan, typically third-line on top of PGA + β-blocker; apraclonidine is mainly used short-term peri-SLT to prevent IOP spikes.

Hallmark feature: high rate of allergic conjunctivitis — 10-15% develop redness/itching/lid swelling within 6 months and must stop. Other points:

• Strict contraindication in infants — toxicity case reports of respiratory depression, somnolence, hypotension
• Elderly drowsiness, dizziness — avoid before driving; consider evening dosing if necessary
• Reasonable β-blocker alternative for asthmatics

④ Carbonic anhydrase inhibitors — topical mild, oral potent but short-term

Topical (Brinzolamide, Dorzolamide) lowers IOP 15-20% with mostly ocular side effects: metallic taste (drainage to mouth), stinging, transient blur. Systemic effects are minimal, but patients with marginal corneal endothelium (Fuchs etc.) face decompensation risk and warrant careful evaluation.

⑤ Rho kinase inhibitors — newer, weaker, unique mechanism

Netarsudil (Rhopressa) and Ripasudil are newer agents that directly relax the trabecular meshwork to enhance outflow — a mechanism distinct from existing drugs. Limited Taiwan availability (Netarsudil rarely marketed; Ripasudil more common in Japan).

Weaker IOP lowering (10-20%) with mainly ocular side effects: over half develop severe hyperemia, subconjunctival hemorrhage (painless redness), and corneal verticillata (slit-lamp visible but vision-sparing). Use case: add-on after multiple agents fail, or alternative for patients with PGA / β-blocker contraindications.

⑥ Pilocarpine — relegated to special indications

Largely reduced role today; almost exclusively used for:

• Acute angle-closure: miotic to open angle (caution: only after other agents have lowered IOP — earlier dosing worsens ciliary ischemia)
• Pre-LPI miosis
• Rare special indications (juvenile glaucoma, post-op IOP spikes, etc.)

Why is it less used? Miosis causes poor night vision; sustained ciliary contraction induces myopia; headache and brow ache are common. Most importantly: pilocarpine can precipitate retinal detachment in high myopia — the principal reason it has fallen out of long-term use.

⑦ Preservative BAK — the hidden long-term toll

Most drops contain BAK preservative; chronic exposure across multiple bottles causes ocular surface epithelial damage, chronic conjunctivitis, dry-eye worsening, and allergic reactions. The key but often-overlooked impact: subconjunctival fibrosis reduces the success rate of future trabeculectomy or MIGS.

5. Fixed-dose combination drops (Taiwan-available list)

When monotherapy is insufficient and two classes are needed, the choice is between two separate bottles or a single combination bottle. Reasons to combine:

① Why use a combination?

1. Better adherence: drops per day cut from 4 to 2, with measurably better compliance
2. Less BAK exposure: two bottles each contain BAK; one combination halves the load
3. Reduces washout: two separate bottles spaced too closely (< 5 min) wash each other out
4. Simpler prescription

② When NOT to combine?

• Want to adjust each agent independently (combos can't be down-titrated)
• Hard to attribute side effects (which component caused it?)
• Need different timing (PGA at night, others in morning)

③ Taiwan-available combination drops

PGA + β-blocker (Timolol) — once nightly

Profile: strongest, most popular, once nightly. Contraindicated in asthma/heart disease (β-blocker limit).

CAI + β-blocker — twice daily

Profile: suitable as the 'third weapon' on top of PGA, or as primary therapy in PGA-intolerant patients. Asthma/heart disease still contraindicated.

α2 + β-blocker — twice daily

Profile: β-blocker + α2 combination, but causes drowsiness in elderly; contraindicated in infants.

CAI + α2 (no β-blocker) — usable in asthma/heart disease

Profile: β-blocker-free — key option when asthmatic or arrhythmic patients need two-class therapy.

PGA + Rho kinase

④ Combination drop strategy

1. Failure on 3 classes (including PGA) → adding a combination bottle outperforms adding a monotherapy (if the new class is novel)
2. Both bottles needed long-term → switch to an equivalent combo to reduce drops and BAK
3. Combo at initial diagnosis? Most guidelines still recommend starting with PGA monotherapy and adding as needed; combo first-line only for very high initial IOP requiring rapid lowering

6. Add-on vs switch — the decision logic

When PGA monotherapy is insufficient, there are two paths: add-on or switch. How to decide?

① When to add

• Partially effective: IOP dropped but not at target (e.g., baseline 24 → 19 on PGA, target 17) → add second class
• Patient can manage multiple bottles (adherence, schedule allows)
• Side effects tolerable

② When to switch

• No effect: barely any IOP change on PGA → try another PGA (inter-individual variability exists) or switch class
• Intolerable side effects: severe redness, marked PAP → switch to latanoprost/tafluprost or non-PGA
• Allergy: switch to PF or different class

③ Mono-ocular drug trial

In some scenarios (uncertain drug efficacy), the clinician may put the new drug in one eye while keeping the old drug in the other for a period, then compare IOP. This isolates the drug effect more cleanly than switching both eyes simultaneously (controlling for diurnal variation, measurement noise, spontaneous IOP fluctuation).

④ Washout considerations

• PGA → another PGA: no washout needed, swap directly
• PGA → non-PGA: 4-6 week washout recommended to re-establish baseline IOP
• Combo → mono: similar to above

7. The role of SLT and repeat treatment

The detailed SLT indications, mechanism and procedure are in Chapter 2. Here we focus on two common clinic questions:

① Does repeat SLT still work?

Yes. Unlike old ALT, SLT doesn't destroy trabecular tissue and is repeatable. Studies show:

• First SLT typically lasts 3-5 years (wide individual variation)
• When effect wanes, repeat SLT achieves comparable response
• Multiple repeats are possible, but if 2-3 rounds fail, escalate to other options

② Do I still need drops after SLT?

Three outcome categories:

• Complete success (IOP at target and stable): can suspend drops, monitor; reintroduce drops only when SLT effect fades
• Partial success: SLT + fewer drops (e.g., from three to one)
• Failure (no meaningful drop): return to drops, consider other options

③ When SLT is not suitable

• Pigment dispersion syndrome, pigmentary glaucoma (excessive inflammation risk)
• Advanced glaucoma needing large IOP drops → SLT usually insufficient
• Active uveitis
• Corneal opacity preventing clear meshwork visualization
• Inability to position (severe cervical spine issues, tremor)

8. MIGS — a complete brand guide

MIGS (Minimally Invasive Glaucoma Surgery) is a fast-evolving field since 2010. Common features: small wound, conjunctiva-sparing, safer, faster recovery, moderate IOP lowering (less than trab). The most common application is combined with cataract surgery — leveraging the cataract incision to add a glaucoma intervention.

① Six-MIGS comparison table

② Per-device key points

iStent inject W (Glaukos) — earliest FDA-approved (2018 W version) trabecular-bypass MIGS with a tiny implant (< 0.4 mm). Combined with cataract surgery yields ~20% additional IOP drop. Conjunctiva fully spared, preserving future trab success.

Hydrus Microstent (Alcon) — 8 mm nitinol scaffold that dilates Schlemm canal over ~90° (combining bypass and channel expansion). HORIZON trial 5-year data shows superiority over cataract surgery alone.

XEN Gel Stent (AbbVie) — most trab-like mechanism: gelatin tube drains aqueous from anterior chamber to subconjunctival space, forming a small bleb. Outpatient under local anesthesia with fewer complications than trab; some need post-op 5-FU. Caveat: conjunctiva is breached, potentially reducing future trab success.

PreserFlo MicroShunt (Santen) — FDA-approved 2023, subconjunctival drainage similar to XEN but made from SIBS biocompatible polymer; stiffer and more positionally stable, with lumen/length engineered to avoid hypotony. Conjunctiva-involving, with the same future-trab consideration.

Kahook Dual Blade (New World Medical) — pure excisional, no implant: a dual-bladed instrument excises a strip of trabecular meshwork. No foreign-body reaction, lower cost, also useful for pigmentary glaucoma. Slightly weaker IOP lowering than other MIGS but fully spares conjunctiva.

OMNI 360 Surgical System (Sight Sciences) — full 360° treatment (trabeculotomy + canalplasty) rather than focal; theoretically broader effect. Confirm Taiwan availability locally.

⑦ Why was CyPass withdrawn? A cautionary case

CyPass Micro-Stent (Alcon), FDA-approved 2016, was a suprachoroidal MIGS device. But the COMPASS-XT 5-year extension found significant corneal endothelial cell loss, prompting voluntary global withdrawal in 2018.

Lesson: 'minimally invasive' doesn't equal long-term safety. Newer MIGS aren't necessarily better than those with 5-10 years of data.

⑧ MIGS practical principles

1. Mild-moderate OAG only, not advanced: advanced disease needs aggressive lowering — MIGS usually insufficient
2. Combined with cataract = ideal timing: gain a MIGS without an extra incision
3. Conjunctiva preservation matters: future trab fares better with virgin conjunctiva (a key consideration with subconjunctival-drainage MIGS like XEN/PreserFlo)
4. Cost & NHI: most MIGS in Taiwan are self-pay; pricing varies by device and hospital from tens of thousands NTD to over 100k (consult the operating hospital)
5. Not a panacea: failed MIGS may still require trab or tube shunt

9. Traditional surgery ladder

① Trabeculectomy — still the gold standard for advanced disease

• Oldest (since 1968), strongest IOP-lowering: can reach < 10 mmHg; some patients off all drops
• Mechanism: a guarded scleral flap allows aqueous to drain into a subconjunctival bleb
• NICE 2022 lists it as first-choice for advanced COAG
• PTVT trial (AJO 2022) 3-year data: trab achieves stronger IOP reduction and fewer drops than tube as primary surgery; overall success rates comparable
• Complications: early bleb leak, hypotony, infection (blebitis, endophthalmitis); late encapsulation failure, accelerated cataract, vision loss
• Close follow-up (every 1-2 weeks for first 2 months, then taper)
• Long-term bleb infection risk (annual endophthalmitis ~0.2-0.5%)

② Tube shunt (Ahmed / Baerveldt)

• For: failed trab, complex cases (uveitic, neovascular, post-corneal-transplant, post-trauma), pediatric glaucoma
• Two main brands:
• PTVT: 5-year success rates comparable to trab; failure modes differ (less bleb infection but tube migration / endothelial loss)
• Complications: tube migration, endothelial loss, diplopia (compression on extraocular muscles)

③ Cyclophotocoagulation

• Mechanism: laser destruction of ciliary epithelium reduces aqueous production rather than enhancing outflow
• Three modalities:
• Not first-line surgery; reserved for failed prior surgeries or eyes with poor visual prognosis

④ When to escalate from drops/laser to traditional surgery?

• 3 classes (including PGA) + SLT, IOP still not at target
• Visual field continues to progress (≥ 2 consistent 24-2 fields over 6 months)
• OCT shows RNFL thinning beyond normal aging rate
• Uncontrolled IOP after acute angle-closure
• Severe drug side effects preventing continued use

10. The special pathway for angle-closure glaucoma

PACG management differs from OAG because the mechanism is angle closure, not trabecular dysfunction.

① Laser peripheral iridotomy (LPI) — prophylactic or therapeutic?

• Mechanism: a small hole in the peripheral iris allows aqueous to bypass the pupil, relieving pupillary block
• Therapeutic LPI (post-attack or chronic angle-closure): standard care
• Prophylactic LPI (suspect narrow angle, no prior attack): controversial.
  • ZAP trial (Zhongshan Angle Closure Prevention, 2019) showed that while prophylactic LPI reduces acute attacks, absolute risk is low — routine prophylaxis isn't clearly superior to observation
  • Current trend: prophylactic LPI for high-risk (clear narrow angle + family history + Asian ancestry); observation for lower-risk

② EAGLE trial: cataract surgery as treatment for PACG

EAGLE trial (Lancet 2016) reshaped angle-closure management: 419 PACG/PAC patients randomized to LPI + medical therapy vs primary lens extraction (+ IOL).

• 3-year: lens extraction arm had better IOP control, higher quality of life, less need for further IOP-lowering interventions
• Conclusion: for PACG/PAC patients with even mild lens opacity, early lens extraction + IOL is a reasonable first-line approach (no need to wait for vision to drop)

③ Practical PACG management in Taiwan

1. Acute attack: medical IOP control (oral acetazolamide, α2, β-blocker) → pilocarpine (after IOP drops) → LPI or paracentesis → consider lens extraction
2. Chronic / progressive after LPI: evaluate lens extraction + possible combined MIGS (goniosynechialysis) depending on angle status
3. PAC (narrow angle without prior attack): prophylactic LPI for high-risk; observation otherwise

11. Taiwan-specific considerations

① Disproportionately high NTG share

Local studies (including the Shihpai Eye Study) consistently show most Taiwanese glaucoma patients have IOP within the 'normal' range. Implications:

• The 'IOP > 21' cutoff misses many patients
• Optic nerve (fundus / OCT) and visual fields matter more than IOP alone
• Targets need stronger individualization (CNTGS proved 30% reduction helps NTG too)

② Higher PACG share than Western populations

Taiwanese and East/Southeast Asian populations have shorter axial lengths and shallower anterior chambers; PACG is 2-3× more prevalent than in Western populations. Practical implications:

• Gonioscopy at initial visit is critical
• Lens extraction has elevated role in PACG (EAGLE-supported)
• Cataract evaluation in elderly should include angle-closure risk assessment

③ Taiwan NHI coverage (three tiers)

• Mostly covered: most PGAs, β-blockers, α2 agonists, CAIs as monotherapy and standard combinations (Cosopt, DuoTrav, Ganfort, Combigan, Xalacom); trabeculectomy; acute angle-closure laser treatment
• Hospital-dependent / partial: SLT, preservative-free formulations, some newer combinations
• Mostly self-pay or restricted: MIGS devices (iStent, Hydrus, XEN, PreserFlo, Kahook), premium PF formulations, Rho kinase inhibitors (mostly self-pay); latanoprostene bunod (Vyzulta) is NHI-covered with restricted criteria

* Actual coverage follows the latest National Health Insurance Administration announcement and hospital-specific rules; this article describes general tiers only.

④ Considerations for remote-area patients

Taiwanese patients in mountainous regions, outer islands and rural areas face:

• Difficulty with monthly clinic visits → poor adherence
• Limited access to perimetry equipment
• SLT or early lens extraction + MIGS particularly suited here → reduces long-term drop dependence
• Also consider 3-month prescriptions and PF formulations (preserve ocular surface)

③ Taiwan NHI coverage rules (April 2026)

Section 14.1 'Anti-glaucoma drops' of the Taiwan NHI Drug Coverage Regulations (April 2026 version) is summarized below. Confirm latest at the NHIA website.

Prescription rules — key points:

• Chronic prescriptions limited to ophthalmologists (since June 2025), with IOP value documented at the visit
• Non-ophthalmologists can prescribe at most 1 month at a time, with patient self-monitoring + ophthalmology referral within 3 months
• No co-administration within same class (e.g., can't use two PGAs or two β-blockers simultaneously)
• Remote areas: per NHI's Telemedicine Coverage Plan, local + ophthalmologist via video can jointly prescribe chronic refills

What this means for patients in practice:

• NHI prefers β-blockers as first-line — clinically PGAs are often preferred (better efficacy, once-daily convenience), but NHI requires prior β-blocker failure/contraindication/intolerance documented. The physician judges based on individual context
• Fixed combinations require failed monotherapy first under NHI — patients wanting fewer drops need prior monotherapy on record; direct combination = self-pay
• Preservative-free single-dose units are gentler for long-term use, ocular surface sensitivity, or coexisting DED; NHI covers — discuss with your ophthalmologist
• SLT laser, MIGS, traditional glaucoma surgery are not in drug coverage; some are NHI-covered (procedure fee + standard supplies), some are self-pay (specialty devices like iStent, XEN gel stent). Discuss specifics with your ophthalmologist

* Source: NHIA Drug Coverage Regulations, April 2026, Section 14.1 Anti-glaucoma drops (14.1.1 monotherapy, 14.1.2 combinations). Surgical procedures are covered under separate medical-payment regulations, not in the drug regulations referenced here.

12. 8 common decision-making Q&As

Closing

Glaucoma treatment is a marathon, not a sprint. From new diagnosis (SLT or PGA), to add-on or switch, to laser, MIGS, or trab — every decision isn't 'better' or 'worse', but an individualized integration of target IOP, side-effect profile, lifestyle, adherence, and NHI/economic burden.

After reading, hopefully you can have a deeper conversation with your doctor at the next visit:

• Ask why this drug (understanding boosts adherence)
• Ask how to monitor side effects (PAP, allergy, systemic effects)
• Ask what's next (if this isn't enough, what's the next step?)
• Ask about NHI vs self-pay differences (avoid unnecessary 'upgrades')

A doctor's job isn't just writing prescriptions — it's walking with you through this optic-nerve preservation campaign. Understanding the full treatment ladder is the best preparation a patient can do.