13 Clinical Trials Summary
13.0 Introduction
13.1 Cornea
13.2 Cataract
13.3 Medical Retina – Age-Related Macular Degeneration (AMD)
13.4 Medical Retina - Diabetes
13.5 Medical Retina – Retinal Vein Occlusion (RVO)
13.6 Vitreoretinal Surgery
13.7 Glaucoma
13.8 Oculoplastics
13.9 Paediatrics
13.10 Neuro-Ophthalmology
13.11 Ocular Oncology
13.7 Glaucoma
GLT [lxix]
Glaucoma laser trial
Newly diagnosed OAG: No difference between ALT and drops (superseded by SLT). ALT as effective as timolol 0.5% at 7yrs
Spaeth, G.L. 1985. The Glaucoma Laser Trial (GLT). Ophthalmic Surg 16(4) 227-228.
EMGT [lxx]
Early Manifest Glaucoma Trial
Newly diagnosed OAG: Decreasing IOP by 25% reduces progression by 1/3 (ALT + betaxolol vs. nothing), 45% of treated still progressed. Treatment delayed progression by 18 months
Leske, M.C., Heijl, A., Hyman, L. et al. 1999. Early Manifest Glaucoma Trial: design and baseline data. Ophthalmology 106(11) 2144-2153.
CIGTS [lxxi]
Collaborative Initial Glaucoma Treatment Study (Early)
Newly diagnosed OAG: Initial treatment with drops or trab
Drops = trab for initial Rx of newly diagnosed OAG (regarding VF loss)
Trab lower IOP but higher risk vision loss and cataract progression
Individualised target IOP (medical, laser or surgery) reduces progression of OAG (fixed reduction inadequate)
(Reversibility of cupping) – more in surgery
Eyes with variability of IOP do better with surgery
Patients with advanced glaucoma do better with surgery
Lichter, P.R., Musch, D.C., Gillespie, B.W. et al. 2001. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology 108(11) 1943-1953.
CNGTS [lxxii]
Collaborative Normal Tension Glaucoma Study
NTG: Decreased IOP by 30% by any means reduces progression by 2/3 (35% → 12%) [Pilo/ALT/Trab]
Risk factors for NTG prevalence (not progression): disc haemorrhage, female, migraine
1998. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group. Am J Ophthalmol 126(4) 487-497.
AGIS [lxxiii]
Advanced Glaucoma Intervention Study
Advanced OAG: ALT vs. trabeculectomy
ALT superior for African-American, trabs superior for Caucasians
No progression if IOP always < 18 or little fluctuation
Eyes with early average IOP > 17.5 had worsening of VF progression compared with IOP < 14
OHTS [lxxiv]
Ocular Hypertension Treatment Study IOP 24-32 one eye, 21-32 other eye
Ocular Hypertension: Decreased IOP by any medication by 20% halves progression to OAG (10% → 5%) NNT = 20 Risk factors for progression:
- Thin CCT <555um
- Older age
- Larger vertical CDR
- ↑ IOP
- Greater HVF PSD
Confirmed by European Glaucoma Prevention Study
Gordon, M.O., Beiser, J.A., Brandt, J.D. et al. 2002. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch Ophthalmol 120(6) 714-720; discussion 829-730.
TUBE vs. TRAB [lxxv]
Primary trab failed or previous cataract surgery (NOT for secondary glaucoma)
Tube – lower failure rate, less additional surgery.
Both had equal IOP reduction and use of supplemental therapy
Can achieve low IOP with tubes (mean 14mmHg)
Gedde, S.J., Schiffman, J.C., Feuer, W.J. et al. 2012. Treatment outcomes in the Tube Versus Trabeculectomy (TVT) study after five years of follow-up. Am J Ophthalmol 153(5) 789-803.e782.
EAGLE [lxxv]
CLE (clear lens extraction) vs LPI/drops/trab
PACG (IOP > 21) or PAC (IOP > 30) without cataract:
- LPI, drops and trabeculectomy is still effective
- CLE is better than standard of care from a QOL perspective
- CLE gives: more significant IOP reduction, less drops, less surgery
Azuara-Blanco, A., Burr, J., Ramsay, C. et al. 2016. Effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma (EAGLE): a randomised controlled trial. Lancet 388(10052) 1389-1397.
UKGTS [lxxvii]
Lantanoprost vs placebo
Phase III for UK to approve xalatan:
- Progression in 15% xalatan vs 26% placebo over 2 years (very short trial)
- Time to progression faster in placebo group
- ↓ IOP 3.8 with xalatan cf. 0.9 with placebo
- Not all glaucoma patients need to be treated
- Side effects, even in placebo group
Garway-Heath, D.F., Crabb, D.P., Bunce, C. et al. 2015. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. Lancet 385(9975) 1295-1304.
LOGTS [lxxviii]
Brimonidone vs timolol
Used as evidence for neuroprotection but many problems with this study limit applicability
Consider brimonidine as a second-line agent in a patient who is progressing despite good IOP and surgery is not appropriate
High drop-out rate in brimonidine group due to side effects
Krupin, T., Liebmann, J.M., Greenfield, D.S. et al. 2011. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol 151(4) 671-681.
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