The CNTG trial: Intra-ocular pressure reduction slows progression of normal-tension glaucoma [Classics Series]

Classics Series, Landmark Trials in Medicine

1. Reduction of intra-ocular pressure (IOP) with topical medications in normal-tension glaucoma significantly reduced risk of progression to visual field impairment and/or optic disc damage.

Original Date of Publication: July 1998

Study Rundown: Increased intraocular pressure (IOP) is known to be a significant risk factor for glaucoma. However, some patients with glaucoma demonstrate normal IOP, known as normal tension glaucoma (NTG). Prior to the Collaborative Normal Tension Glaucoma (CNTG) study, it was unclear whether reducing IOP would be beneficial in this subset of patients as well. The CNTG trial randomized approximately 140 patients with NTG to observation or IOP-lower treatments. After an average of eight years of follow-up, the study found that lowering IOP significantly reduced the incidence of visual field impairment and/or optic disc damage compared to control. Cataracts occurred at a substantially higher rate in the treatment group, potentially cofounding the result; however, the significant benefit of reducing IOP in NTG patients remained after statistical correction. Limitations include that providers were not blinded to randomization, although the outcome assessors were masked. In addition, not all patients in the observation arm were randomized, and the time required to reach the goal of 30% IOP decrease was prolonged. Sample size was also quite limited compared to other randomized controlled trials in ophthalmology. Nonetheless, this study demonstrates that IOP reduction even in NTG patients may be beneficial.

Click to read Part I in the American Journal of Ophthalmology

Click to read Part II in the American Journal of Ophthalmology

In-Depth [randomized controlled trial]: Approximately 140 patients diagnosed with NTG (normal IOP with optic disc abnormalities) were randomized to the observation arm or treatment arm involving the use of topical ocular antihypertensive drops and/or filtration surgery to decrease IOP by 30%. Patients were evaluated every 3-6 months with optic disc imaging and visual field testing. If the patient were thought to have glaucomatous progression, images were forwarded to a masked review committee, which would confirm the findings. Kaplan-Meier survival analysis showed that after correction, mean survival time was 2,049 ± 129 days and 1,427 ± 139 days in the treatment and observation arms, respectively (p=0.005). A significantly higher rate of cataract was found in the treatment arm (38% vs. 14%, p=0.0011), which affected visual field testing. When the data was corrected for this confounder, the significance of IOP lowering treatment still remained (p=0.0034). IOP lowering therefore may be beneficial in delaying the progression of glaucoma even in NTG patients.

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