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Evidence Based Medicine: Glaucoma Studies

The Ocular Hypertension Treatment Study


  • The Ocular Hypertension Treatment Study (OHTS) determined whether topical ocular hypotensive medications are effective in delaying or preventing the onset of primary open-angle glaucoma (POAG) in patients demonstrating no signs of glaucomatous damage


  • 1636 patients with IOPs ranging from 24-32 mmHg in one eye and 21-32 mmHg in the other eye were selected to receive treatment (any type of commercially available topical hypotensive. 817 patients), or observation (no treatment, 819 patients)

  • Goal: Reduce IOP by 20% or more in treated group


  • The mean IOP reduction in the group that received treatment was 22.5% compared to the group that did not receive treatment (4%)

  • At the five-year follow-up, the probability of developing POAG was 4.4% in the treated group vs. 9.5% in the group left untreated.

  • Repeatable visual field defects and optic nerve head deterioration was less noticeable in the treated group


  • Ocular hypotensives were very effective in delaying/preventing the onset of POAG in individuals with NTG

  • In a subsequent OHTS report, central corneal thickness (CCT) was found to be a powerful predictor for development of POAG; the risk of POAG was inversely related to CCT. Patients with CCT < 555um were three-times more likely to develop POAG than patients with CCT> 588um.


Glaucoma Laser Trial


  • The Glaucoma Laser Trial (GLT) compared the safety and efficacy of argon laser trabeculoplasty (ALT) as an alternative to topical glaucoma drops as initial therapy in treating patients with POAG


  • 271 patients with newly diagnosed glaucoma

  • One eye received timolol maleate 0.5%; the fellow eye was treated with ALT


  • 2-year follow-up: Eyes treated with ALT had a 1-2 mmHg additional IOP decrease and required fewer prescriptions of two or more medications compared to eyes treated with timolol maleate 0.5% alone.

  • 44% of eyes at the end of two years were controlled by ALT alone

  • 70% of eyes at the end of two years were controlled by ALT and timolol maleate 0.5%

  • 30% of eyes at the end of two years were controlled with timolol maleate 0.5% alone

  • Visual acuity and visual field testing showed no significant difference between the two groups

  • At the seven and nine-year follow-ups, no significant differences in CD ratios were noted between the two groups


  • This study was completed prior to the advent of prostaglandin analogues, topical CAIs, and alpha-agonisits, but suggests ALT may be an alternative as initial glaucoma therapy


The Collaborative Normal-Tension Glaucoma Study


  • The Collaborative Normal-Tension Glaucoma Study (CNTGS) aimed to determine whether IOP is a factor in the pathogenesis of normal-tension glaucoma (NTG).


  • 140 patients with NTG and high-risk VF defects: 79 (56%) eyes were randomized to receive no treatment. 61 (44%) eyes were randomized to receive treatment (medications, laser, and/or surgery to decrease IOP 30% from baseline)


  • Compared to the untreated group, there was a statistically significant favorable effect in eyes that had an IOP reduction of 30% or greater from baseline on visual field and optic nerve deterioration.

  • 65% of patients in the untreated group showed no progression of their disease in the follow-ups


  • IOP is involved in the pathology of NTG, therapy is effective in lowering IOP, and a 30% reduction is beneficial to patients to prevent glaucoma from progressing.

  • Because a significant amount of patients left untreated showed no exacerbation of their disease at follow-ups, a choice of therapy must be carefully thought out.



Collaborative Initial Glaucoma Treatment Study


  • The Collaborative Initial Glaucoma Treatment Study (CIGTS) sought to determine if medication or filtering surgery (trabeculectomy) was more beneficial as initial treatment of glaucoma.


  • 607 patients with newly diagnosed open angle glaucoma

  • One eye from each patient was selected to receive topical medication; the other eye underwent surgery (trabeculectomy)

  • Patients were evaluated every six months for five years


  • Visual field loss did not significantly differ between the two groups after five years

  • Surgically treated patients had an initial increased risk of substantial visual acuity loss compared with eyes treated topically

  • At the four-year follow-up average visual acuities between the two groups were the same

  • The surgically treated group had on average a 3.5 mmHg additional IOP decrease compared to the topically treated group, but had a greater rate of cataract surgery


  • Initial medication and surgical treatment showed similar end-results in visual field outcomes and final visual acuities

  • Aggressive IOP lowering in both groups minimized visual field loss

  • The researchers concluded that changing the recommended “medication first” approach was not warranted


Early Manifest Glaucoma Trial


  • The Early Manifest Glaucoma Trial (EMGT) compared the effect of immediately lowering IOP vs no treatment of later treatment on the progression of newly detected open-angle glaucoma (OAG)




  • A significant amount of patients diagnosed with NTG were randomized to receive treatment (laser trabeculoplasty plus topical betaxolol) or no treatment.


  • Treatment lowered IOP by roughly 5 mmHg (25% reduction)

  • Glaucomatous progression was seen less frequently in treated patients (45%) compared to those patients that were not treated (62%).


  • After six years, glaucomatous progression was less in the treated vs untreated group

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