Why Do People (Still) Go Blind from Glaucoma?

Glaucoma is a progressive optic neuropathy and is the leading cause of irreversible blindness worldwide. Over 60 million people were estimated to be affected with open-angle glaucoma (OAG) in 2010, and bilateral blindness from the disease was estimated to be present in 4.5 million people with OAG in 2010, rising to 5.9 million people in 2020.1 In 1982, Grant and Burke2 published an article with a title similar to the present article suggesting three potential reasons why people go blind from glaucoma: one-third were undiagnosed; one-third had not been treated properly; and one-third were noncompliant with therapy. They also noted that, when abnormalities ranging from early glaucomatous cupping to advanced visual field defects were present at initial evaluation, progressive visual field loss continued to occur even with lowered intraocular pressure (IOP). In the consensus of Medical Treatment of Glaucoma by the World Glaucoma Association, the definition of target IOP includes the need to adjust therapy based on numerous factors, among them the initial level of damage, rate of progression, and life expectancy.3 It appears that eyes with more severe damage at presentation require lower IOP to prevent further functional loss or blindness. Forchheimer et al.4 investigated the relationship between baseline visual field damage, IOP, and rate of progression and found that among eyes with more severe functional damage (mean deviation MD worse than −12 dB), those with mean follow-up IOP < 14 mmHg progressed more slowly than those with higher pressures. Kotecha et al.5 found that following trabeculectomy, eyes showing changes in both optic nerve and visual field sensitivity had less IOP reduction from baseline compared with eyes showing no progression. Lee et al.6 reported that patients with more severe glaucomatous damage, as measured by both visual field and optic disc cupping, are at highest risk for rapid worsening of the disease and that more aggressive treatment of such patients should be considered to prevent visual disability. Heijl et al.7 showed that treatment is more effective in patients with MD better than −4.5 dB compared to patients with MD worse than −4.5 dB. Thirty years later, despite meaningful improvements in technology, therapeutic tools, and knowledge of the disease, patients continue to go blind from glaucoma. In a retrospective chart review by Peters et al.8 in Sweden, at the time of the last visit 42.2% and 16.4% of patients had at least one eye blind or bilateral blindness from glaucoma, respectively. Overall, the cumulative incidences of blindness in at least one eye and bilateral blindness from glaucoma were 26.5% and 5.5%, respectively, after 10 years, and 38.1% and 13.5% at 20 years.8 A recent report of the population-based study of all residents of Olmsted County, Minnesota,9 showed that the 20-year probability and the population incidence of blindness due to OAG in at least one eye decreased over the 45 years from 1965 to 2009. They also suggested that “… a subset of patients with glaucoma may have more aggressive disease and may be particularly susceptible to progression, possibly because of non-IOP-related factors that contribute to retinal ganglion cell (RGC) death and vision loss.”4 Although there is compelling evidence that “non-IOP-related factors” may indeed have a significant role in glaucoma pathogenesis,10–12 IOP is the major component associated with fast progression rate.13 In a recent review on the pathophysiology of glaucoma, Weinreb et al.14 stated that although the loss of ganglion cells is related to the level of IOP, other factors may also play a role. To date, there is no high-level evidence that non-IOP lowering medications can alter the progression of glaucoma. Yet, it is possible that other treatments may be needed to supplement IOP lowering or to make a given amount of IOP lowering more effective. Our working hypothesis is that even after 30 years of substantial advances in the field, the challenges faced by patients and eye care providers to prevent blindness due to glaucoma have not changed as substantially.