Glaucoma, the prevalence of which is increasing worldwide, is the second leading cause of blindness globally and the third in India. It is characterized by a group of ocular conditions which lead to optic nerve damage and loss of visual function. It has a significant impact on patients’ health-related quality of life (HRQoL) and also adds to the societal economic burden. [15]
Increasing age is a major risk factor for primary open-angle glaucoma. Most of the patients enrolled belonged to the age group of 41-65 years with no statistically significant difference between the two treatment groups (p = 0.167). The mean age was 60 ± 11 years in the timolol group and 55.2 ± 12.8 years in the latanoprost group. These results correlate with the visual impairment project and a number of other epidemiological studies which show that the prevalence of glaucoma increases dramatically with age especially after the age of 40 years. [18, 19, 20] This might be due to the decline in retinal ganglion cell number and reduced neural capacity. Thus, in older individuals, fewer ganglion cells need to be lost before there is detectable visual field loss. An alternate hypothesis is that, ageing may increase the inherent vulnerability of ganglion cells to IOP insult. [21] As the risk of glaucoma increases substantially with age, the number of those at risk of glaucoma is expected to grow exponentially over time with increasing life expectancy in India. Studies of gender influence on glaucoma prevalence have been conflicting. In the current study, there were a total of 28 males and 32 females among the study population with no statistically significant difference. This is consistent with the results obtained in both the studies conducted in urban and rural south Indian population where, no significant statistical association between gender and glaucoma prevalence was found. [6, 22] While a Bayesian meta-analysis conducted by Rudnicka A R et al and the ACES study reported higher rates of POAG amongst males, The Blue Mountains Eye Study conducted by Mitchell P et al reported higher rates in females. [23, 5, 24]
Although high IOP, advancing age, positive family history and ethnicity are the best established risk factors, a number of potential new risk factors have been identified more recently. People with diabetes are twice as likely to develop glaucoma as are non-diabetics. The evidence from experimental studies suggests that this may be attributed to enhanced susceptibility of the eye to stress and compromised autoregulation in diabetes. Widespread vascular damage in diabetes may also exacerbate the ischaemic insult seen in glaucoma. [21] While the meta-analysis conducted by Bonovas S et al and the Blue Mountains Eye Study reported a significant and consistent association between diabetes mellitus and glaucoma, the Rotterdam study and the Baltimore Eye Survey have failed to find any positive association. [25, 26, 27, 28] The evidence for the effect of blood pressure on glaucoma remains controversial due to their complex relationship. Higher systolic and mean arterial blood pressures were associated with a higher prevalence of POAG in The Los Angeles Eye Study. [29] The Blue Mountains Eye Study, the Egna-Neumarkt Glaucoma Study and the Rotterdam Eye Study also found that systemic hypertension increases the susceptibility to glaucoma, possibly due to a positive correlation between blood pressure and IOP. [30, 31, 32] Despite this positive correlation, the actual change in IOP with increasing blood pressure is small. It is also a counter intuitive association given that a high blood pressure should produce a high ocular perfusion pressure and thus give a protective effect. [21] Indeed, other epidemiological studies like the Barbados Eye study and the Early Manifest Glaucoma trial have found a greater prevalence of glaucoma in people with low blood pressure and suggest that systemic hypertension could actually be a protective factor, consistent with the possibility that low ocular perfusion pressure injures ganglion cells [33, 34] Among the 60 patients suffering from POAG enrolled in the present study, 13 of them were diabetic, 11 were hypertensives and 5 subjects had both diabetes and hypertension. But to draw conclusions from this study would not be apt given the limited number of participants and the complex and controversial associations between diabetes, hypertension and glaucoma.
There were 15 smokers and 28 alcoholics among the 60 subjects in this study. A small increase in IOP among smokers was also noted in The Blue Mountains Eye Study. [35] But, the prevalence of POAG has not been observed to vary between smokers and non-smokers in other studies. [36, 37] In a study conducted by Kang J H et al it was reported that alcohol consumption did not increase the risk of POAG. [38]
The most important and the only proven modifiable risk factor for glaucoma is increased intraocular pressure. [16] The role of IOP reduction in preventing optic nerve damage and visual loss has been upheld in numerous randomized prospective trials. Medical therapy is the standard of care in primary open angle glaucoma and also the mainstay of initial and long term IOP reduction in other types of glaucoma. [17] Although topical blockers are the first line drugs in the management of glaucoma, in recent times they have been replaced by prostaglandin analogues.
Evaluation of efficacy was the primary objective of this study. The baseline mean IOP was comparable between the two groups (p = 0.354). There was a significant reduction in mean IOP at 12 weeks in both timolol (6.77 ± 1.48 mmHg, 25.9%) and latanoprost (7.97 ± 1.27 mmHg, 31.25%) groups but it was significantly greater (p < 0.0001) with latanoprost 0.005% administered once daily in the evening compared to timolol 0.5% administered twice daily. Hence latanoprost was found to be a more potent and effective ocular hypotensive than timolol.
Similar outcomes were noted in a meta-analysis of randomised controlled trials comparing latanoprost with timolol conducted by Zhang W Y et al who found that both latanoprost 0.005% administered once daily and timolol 0.5% administered twice daily reduced IOP. However, latanoprost (30.2%) showed better IOP lowering effect compared to timolol (26.9%). [3] The study results were also consistent with a pooled-data analysis of three randomized double-masked studies done by Hedman K et al in which a 1.2 mmHg more reduction (p < 0.0001) in diurnal IOP was seen with latanoprost compared to timolol. [14] Similar observations were also made in studies from India, Egypt and the Philippines [11, 12, 39] The Scandinavian Latanoprost Study Group, The UK Latanoprost Study Group and The United States Latanoprost study group have also upheld these findings. [40, 41, 42] In another long-term cost and efficacy analysis done in Germany, though patients on latanoprost and timolol had similar clinical outcomes, patients in the timolol group required more medications and more frequent therapy changes compared to those in the latanoprost group. [43]
Another way to evaluate the clinical efficacy of different ocular hypotensive drugs is to analyse the number of patients reaching a specific target IOP. In this study significantly more eyes (2 = 4.6, df = 1, p = 0.032) treated with latanoprost (46, 76.6%) achieved target IOP as compared to those treated with timolol (35, 58.3%). These results are in line with the study conducted in the Philippines. [12]
The adverse effects encountered were mild to moderate local ocular adverse effects and there was no statistically significant difference between the groups (p = 0.54). There were no serious adverse effects observed in either group and both study medications were well tolerated. Conjunctival hyperaemia was seen in more number of patients receiving latanoprost compared to patients receiving timolol but was not statistically significant. Increased iris pigmentation, which is a known side effect of prostaglandin analogues was not seen in the latanoprost treated patients in this study. While a similar adverse effect profile was also seen in studies conducted in Egypt and the Philippines, a significantly higher incidence of conjunctival hyperaemia and iris pigmentation was noted in patients treated with latanoprost compared to timolol in the meta-analysis and few other studies mentioned earlier. [11, 12, 3, 40, 41, 42] Failing to find increased iris pigmentation in the present study could be due to the dark irides of the study subjects or short study duration.
There were no systemic side effects observed in both the treatment groups during the study, though according to previous studies latanoprost is said to be associated with lesser systemic side effects. [42] Ophthalmic timolol has been reported to reduce blood pressure, cause bradycardia and bronchospasm in patients with cardiovascular or pulmonary disorders warranting caution in its use. [3]
Prostaglandin analogues have also been reported to lower nocturnal IOP, have a persistent therapeutic effect and a lesser non-responder rate compared to timolol in other studies. [14] Hence they have now become the most popular ocular hypotensives. In this context, such studies would be valuable in decision making of glaucoma management. However, short time frame and open labeled design are the limitations of this study. Also, since glaucoma is a chronic disease, it would be preferable to evaluate the cost-effectiveness of the IOP lowering agents over a longer time period as latanoprost though more effective than timolol, is also more expensive.
Conclusion
The prostaglandin analogue latanoprost was shown to have a higher documented efficacy in the form of additional 1.2 mmHg decrease in IOP with more number of eyes reaching target IOP, similar patient tolerability as timolol and a convenience of once daily dosing. Hence latanoprost is a preferable and effective option for the management of primary open angle glaucoma.