Smoking Intensity is Associated With Progressive Optic Nerve Head Vessel Density Loss in Glaucoma.

PRCIS: A lifetime history of greater smoking consumption was associated with faster vessel density loss over time. Smoking intensity should be considered when assessing the risk of glaucoma progression, as well as its management. PURPOSE: To investigate the relationship of smoking and smoking intensity, with the rate of optic nerve head (ONH) whole image capillary density (wiCD) loss in primary open angle glaucoma (POAG) and glaucoma suspect patients. METHODS: In this longitudinal study, patients with POAG who had at least 2 years of follow-up and optical coherence tomography angiography (OCTA) performed at a minimum of 4 visits were selected for study. The smoking intensity was calculated as the pack-year at the baseline OCTA. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on the rates of wiCD loss over time. Nonlinear least-squares estimation with piecewise regression model was used to investigate the cutoff point for the relationship between wiCD loss and smoking intensity. RESULTS: One hundred sixty-four eyes (69 glaucoma suspect and 95 POAG) of 110 patients were included with a mean (95% CI) follow-up of 4.0 (3.9 to 4.1) years. Of the 110 patients, 50 (45.5%) had a reported history of smoking. Greater smoking intensity was associated with faster wiCD loss [-0.11 (-0.23 to 0.00)] %/year per 10 pack-year higher; P =0.048) after adjusting for covariates. The wiCD thinning became significantly faster when smoking intensity was greater than 22.2 pack-years. Smoking had no effect on the rate of wiCD thinning in patients who smoked <22.2 pack-years during their lifetime. CONCLUSIONS: A history of greater smoking consumption was associated with faster vessel density loss, suggesting smoking intensity as a potential risk factor for glaucoma.

Impact of smoking on glaucoma.

PURPOSE OF REVIEW: Assessing whether lifestyle related factors play a role in causing primary open-angle glaucoma (POAG) is of great value to clinicians, public health experts and policy makers. Smoking is a major global public health concern and contributes to ocular diseases such as cataracts, and age-related macular degeneration through ischemic and oxidative mechanisms. Recently, smoking has been investigated as a modifiable risk factor for glaucoma. In the presence of an association with glaucoma, provision of advice and information regarding smoking to patients may help reduce the burden of disease caused by POAG. Therefore, the aim of this review is to summarize the current evidence regarding the effect of smoking in the pathogenesis of glaucoma and its incidence, progression as well as the benefits of smoking cessation. RECENT FINDINGS: While the association between glaucoma development and smoking history is controversial, in the last decade, several recent studies have helped to identify possible effects of smoking, especially heavy smoking, in regard to glaucomatous progression. Smoking cessation may possibly be protective against glaucoma progression. SUMMARY: Smoking may play a role in glaucoma progression and long-term smoking cessation may be associated with lower glaucoma progression. The dose-response relationship between smoking and glaucoma as well as therapeutic potential of smoking cessation needs to be further validated with both preclinical and rigorous clinical studies.

Associations of smoking and alcohol consumption with the development of open angle glaucoma: a retrospective cohort study.

OBJECTIVES: To investigate the associations of alcohol consumption and smoking with the development of perimetric glaucoma in patients with suspected glaucoma. DESIGN: A retrospective cohort study of patients suspected to have glaucoma enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). SETTING: Three tertiary glaucoma centres in the USA. PARTICIPANTS: 825 eyes of 610 patients with glaucoma suspect eyes with normal visual fields (VF) at baseline were followed over an average of 9 years from the DIGS and ADAGES studies. OUTCOME MEASURES: Development of glaucoma was defined as occurrence of three consecutive abnormal VF tests during follow-up. Univariable and multivariable Cox regression models were used to investigate lifestyle-related factors associated with development of VF loss over time. RESULTS: VF tests were abnormal three times in a row in 235 (28.5%) eyes. Alcohol consumption was associated with a higher risk of developing glaucoma (HR 1.57, 95% CI 1.03 to 2.38, p=0.037). In men, the risk of developing glaucoma in alcohol drinkers (HR 1.92, 95% CI 1.00 to 3.68, p=0.048) was greater than non-alcohol drinkers. In individuals of African descent, the risk of developing glaucoma in alcohol drinkers (HR 1.79, 95% CI 1.02 to 3.15, p=0.043) was greater than non-alcohol drinkers. Age was a modifier of the relationship between smoking and glaucomatous VF defects (p=0.048). The risk of developing glaucoma in smokers (HR 1.73, 95% CI 1.10 to 2.72, p=0.019) was greater than never smokers after adjustment for confounding factors in older patients (age >61 years). CONCLUSION: Alcohol consumption was associated with an increased risk of developing glaucoma, particularly in men and individuals of African descent. The risk of developing glaucoma among smokers suspected of having glaucoma was influenced by age, with older individuals having a higher risk than younger people. TRIAL REGISTRATION NUMBER: NCT00221897 and NCT00221923.

Risk factors for microcystic macular oedema in glaucoma.

BACKGROUND/AIMS: To identify clinical characteristics and factors associated with microcystic macular edema (MME) in patients with primary open-angle glaucoma (POAG). METHODS: We included 315 POAG eyes between 2010 and 2019 with good-quality macular volume scans that had reliable visual fields (VF) available within 6 months in this observational retrospective cohort study. Eyes with retinal pathologies except for epiretinal membrane (ERM) were excluded. The inner nuclear layer was qualitatively assessed for the presence of MME. Global mean deviation (MD) and Visual Field Index (VFI) decay rates, superior and inferior MD rates and pointwise total deviation rates of change were estimated with linear regression. Logistic regression was performed to identify baseline factors associated with the presence of MME and to determine whether MME is associated with progressive VF loss. RESULTS: 25 out of 315 eyes (7.9%) demonstrated MME. The average (±SD) age and MD in eyes with and without MME was 57.2 (±8.7) versus 62.0 (±9.9) years (p=0.02) and -9.8 (±5.7) versus -4.9 (±5.3) dB (p<0.001), respectively. Worse global MD at baseline (p=0.001) and younger age (p=0.02) were associated with presence of MME. ERM was not associated with the presence of MME (p=0.84) in this cohort. MME was not associated with MD and VFI decay rates (p>0.49). CONCLUSIONS: More severe glaucoma and younger age were associated with MME. MME was not associated with faster global VF decay in this cohort. MME may confound monitoring of glaucoma with full macular thickness.

Smoking and progressive retinal nerve fibre layer thinning in glaucoma.

BACKGROUND/AIMS: To investigate the relationship between smoking and smoking intensity, and the rate of retinal nerve fibre layer (RNFL) thinning in patients with primary open angle glaucoma (POAG). METHODS: In this longitudinal study, patients with POAG who had at least 3 years of follow-up with a minimum of 5 visits of optical coherence tomography (OCT) were enrolled. The smoking intensity was calculated as the pack-year at the baseline OCT. Univariable and multivariable linear mixed models were used to determine the effect of each parameter on the rates of RNFL thinning over time. Non-linear least-squares estimation with piecewise regression model was used to investigate the cut-off point for the relationship between circumpapillary RNFL thinning and smoking intensity. RESULTS: A total of 466 eyes of 314 patients were included over the mean (95% CI) follow-up of 6.6 (6.4 to 6.7) years. Of the 314 patients, 121 (39%) had reported any history of smoking. Greater smoking intensity was associated with faster RNFL thinning (-0.06 (95% CI -0.11 to 0.00) µm/year per 10 pack-year higher; p=0.031) after adjusted for confounding factors. RNFL thinning became significantly faster when smoking intensity was >8 pack-year. CONCLUSIONS: Smoking intensity is associated with faster rates of RNFL thinning. Evaluation of smoking intensity might add information to the assessment of risk of glaucoma progression. Future studies are required to explore if withdrawing smoking as a modifiable risk factor can decrease progression in patients with glaucoma.

Smoking Cessation May Reduce Risk of Visual Field Progression in Heavy Smokers.

PRCIS: The earlier a person quits smoking the more likely is the optic nerve be spared from damage. PURPOSE: To investigate the effect of smoking cessation on visual field (VF) progression in glaucoma. METHODS: Primary open angle glaucoma patients with a minimum of 3 years follow-up and 5 VFs were included. Linear mixed models were used to investigate the effects of smoking on the rates of 24-2 VF mean deviation loss after adjusting for confounding factors. Cox proportional hazard regression was used to identify whether different levels of smoking intensity were associated with VF progression with respect to different duration of quitting. RESULTS: Five hundred eleven eyes of 354 patients were included over the mean follow-up of 12.4 years. Mean baseline age (95% confidence interval) was 62.3 (61.2, 63.4) years. One hundred forty nine (42.1%) patients were smokers. In a multivariable model, smoking intensity was associated with faster VF loss (-0.06, 95% confidence interval (-0.10, -0.01) dB/year per 10 pack-years, P =0.01) among smokers. Heavy smokers (≥20 pack-years) who had quit ˂25 years prior had significantly greater odds of VF progression compared with never smokers (odds ratio=2.49 (1.01, 6.08); P =0.046). There was no significant difference in odds of VF progression in heavy smokers who had quit smoking more than 25 years compared with never smokers ( P =0.43). A significantly higher proportion of VF progression was found in heavy smokers who quit < 25 years compared with heavy smokers who quit ≥25 years by Kaplan-Meier analysis ( P =<0.001). CONCLUSIONS: After ≥25 years of smoking cessation, the risk of VF progression in former heavy smokers becomes similar to never smokers. Long-term smoking cessation may be associated with lower VF progression in glaucoma patients.

Effects of Smoking on Optic Nerve Head Microvasculature Density in Glaucoma.

PRCIS: Decreased superficial whole image capillary density was observed in open angle glaucoma (OAG) patients with high smoking intensity. PURPOSE: To investigate the effects of smoking on optic nerve head capillary density measured by optical coherence tomography angiography in patients with OAG. METHODS: In this retrospective cross-sectional study, perimetric and preperimetric glaucoma patients enrolled in the Diagnostic Innovations in Glaucoma Study (DIGS) with optical coherence tomography angiography follow-up were included. Univariable and multivariable linear mixed analysis were performed to determine the effects of different variables on the superficial whole image capillary density. RESULTS: A total of 432 eyes of 271 glaucoma patients comprising 63 preperimetric (106 eyes) and 208 perimetric OAG (326 eyes) were included. A history of tobacco consumption was reported in 105 (38.8%). Among smokers, mean (95% confidence interval) smoking intensity was 12.8 (10.2, 15.5) pack-years. After adjusting for age, glaucoma severity and other confounders, each 10 pack-year increase in smoking intensity (95% confidence interval) was associated with -0.54 (-1.06, -0.02) % lower whole image capillary density ( P =0.041). CONCLUSIONS: Smoking intensity is associated with reduced optic nerve vessel density in glaucoma.

Impact of Smoking on Visual Field Progression in a Long-term Clinical Follow-up.

PURPOSE: To investigate the effect of smoking on rates of progressive visual field (VF) damage over time in glaucoma. DESIGN: Retrospective cohort study. PARTICIPANTS: Five hundred eleven eyes of 354 patients with glaucoma followed up from multicenter glaucoma registries. METHODS: In this longitudinal study, 354 patients with primary open-angle glaucoma with a minimum of 3 years of follow-up and 5 VF tests were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. Univariate and multivariate linear mixed models were used to investigate the effects of smoking on rates of 24-2 VF mean deviation loss. Visual field progression was defined using pointwise linear and significant negative VF mean deviation loss. Logistic regression was used to identify baseline factors and whether different levels of smoking intensity were associated with VF progression. Kaplan-Meier survival analysis and the log-rank test were used to compare the cumulative risk ratio of progression between smoker and never smoker groups. MAIN OUTCOME MEASURES: Visual field progression. RESULTS: Five hundred eleven eyes of 354 patients were included over the median follow-up of 12.5 years. Median baseline age was 64.8 years. Of the 354 patients, 124 (35%) were Black, and 149 (42.1%) and 168 (59.8%) had reported a history of smoking or alcohol consumption, respectively. In a multivariate model, higher smoking intensity was associated with faster VF loss (coefficient, -0.05 decibels (dB)/year per 10 pack-years; 95% confidence interval [CI], -0.08 to -0.01 dB/year per 10 pack-years; P = 0.010). Developing VF progression in eyes of heavy smokers (≥ 20 pack-years) was 2.2 times more than in eyes of patients without smoking history (odds ratio, 2.21; 95% CI, 1.02-4.76; P = 0.044). Statistically significant differences were found between heavy smokers (≥ 20 pack-years) and never smokers by Kaplan-Meier analysis (P = 0.011, log-rank test). CONCLUSIONS: Heavy smokers are more likely to sustain VF loss in eyes with glaucoma. The prospective longitudinal design of this study supports the hypothesis that levels of smoking may be a significant predictor for glaucoma progression. Additionally, this information can be used for clinically relevant tobacco prevention and intervention messages.

Multipressure Dial Goggle Effects on Circumpapillary Structure and Microvasculature in Glaucoma Patients.

PURPOSE: To evaluate the effects of pressure changes induced by a multipressure dial (MPD) on circumpapillary retinal nerve fiber layer (RNFL) and capillary density (CD) measurements in patients with glaucoma using OCT angiography (OCTA). DESIGN: Prospective interventional study. PARTICIPANTS: Twenty-four patients with primary open-angle glaucoma. METHODS: One eye of each patient underwent negative pressure application with the MPD. The MPD alters intraocular pressure (IOP) relative to atmospheric pressure by generating a negative pressure vacuum within a goggle chamber that is placed over the eye. Each participant underwent serial high density OCTA imaging (AngioVue) of the optic nerve head at different negative pressure increments of -5 mmHg, starting from 0 mmHg, ending at -20 mmHg, and then returning to baseline. Images were acquired after 2 minutes of sustained negative pressure at each target pressure to allow for stabilization of the retinal structures and microvasculature. The RNFL thickness and CD measurements were automatically calculated using the native AngioVue software, and then exported for analysis. MAIN OUTCOME MEASURES: The influence of different levels of negative pressure on circumpapillary RNFL thickness and CD measurements, assessed by a linear mixed-effects model with repeated measures. RESULTS: The mean (± SD) age was 71.0 years (± 7.8 years), the baseline IOP was 17.5 mmHg (± 3.6 mmHg), and there was a mean 24-2 mean deviation of -2.80 dB (± 2.55 dB). Serial circumpapillary CD measurements showed a statistically significant dose-dependent increase from baseline, without negative pressure application, to the maximum negative pressure application of -20 mmHg (difference, 2.27%; P = 0.010). Capillary density measurements then decreased symmetrically when lowering the negative pressure to baseline. Circumpapillary CD measurements at target negative pressures of -10 mmHg, -15 mmHg, and -20 mmHg were significantly higher than the baseline measurements (all P values < 0.05). Circumpapillary RNFL thickness remained the same throughout different levels of negative pressure. CONCLUSIONS: Circumpapillary CD measurements showed a dose-dependent increase with the induction of negative pressure, while RNFL thickness measurements remained unchanged.