Interpretation of the glaucoma “landmark studies”

The Ocular Hypertension Treatment study (OHTS),1 the Early Manifest Glaucoma trial (EMGT),2 the Advanced Glaucoma Intervention Study (AGIS),3 the Collaborative Initial Glaucoma Treatment Study (CIGTS)4 and the Collaborative Normal Tension Glaucoma Study (CNTGS)5 are often referred to as the “landmark studies”, as these were prospective, multicentre, masked, randomised controlled trials (RCTs). Objective endpoints were ensured by uniform use of automated perimetry and stereo disc photography. With the cost of the landmark studies reaching US$132 million, it is unlikely they will be repeated. Therefore, accurate interpretation of their findings is vital.

A commonly held belief is that the landmark studies have demonstrated beyond doubt that lowering intraocular pressure (IOP) is of benefit in preventing the onset of glaucoma in ocular hypertension (OH) and in reducing disease progression in eyes with primary open-angle glaucoma (POAG). Reflecting this commonly held interpretation of the landmark studies, Weinreb and Khaw wrote in their seminar on “Primary open-angle glaucoma”6 that “Lowering the intraocular pressure (IOP) prevents progression at early and late stages of the disease. The degree of protection is related to the degree of IOP reduction”.

This interpretation of the landmark studies is unequivocally positive as to the benefits of reducing IOP and encourages efforts to reach a low enough IOP to confer “protection”. The landmark studies certainly imply that lowering IOP is beneficial, but do not suggest that “The degree of protection is related to the degree of IOP reduction”.

For eyes with a baseline IOP less than 32 mmHg, The landmark studies support the following conclusions:

• Lowering IOP is not of proven benefit in either OH or normal tension glaucoma (NTG).1 5

• Lowering IOP is of marginal benefit compared to no treatment in POAG.2

• With treatment of POAG there was no statistically significant relationship between …