Person:

Schaumberg, Debra A.

Objective To estimate the prevalence and risk factors for dry eye disease (DED) among US men.

Methods Cross-sectional prevalence survey among male participants 50 years and older in the Physicians' Health Studies I (N = 18 596) and II (N = 6848). We defined DED as the presence of clinically diagnosed dry eye or severe symptoms (both dryness and irritation constantly or often). We calculated the age-standardized prevalence of DED adjusted to the age distribution of US men in 2004 and projected estimates forward to 2030. We compared DED prevalence with a similar cohort of women and examined associations with possible risk factors.

Results The prevalence of DED increased with age, from 3.90% among men aged 50 to 54 years to 7.67% among men 80 years and older (Pfor trend <.001). High blood pressure (odds ratio, 1.28; 95% confidence interval, 1.12-1.45) and benign prostatic hyperplasia (odds ratio, 1.26; 95% confidence interval, 1.09-1.44) were associated with a higher risk of DED. Use of antidepressants, antihypertensives, and medications to treat benign prostatic hyperplasia were also associated with increased risk of DED. The age-standardized prevalence of DED was 4.34%, or 1.68 million men 50 years and older, and is expected to affect more than 2.79 million US men by 2030.

Conclusions Dry eye disease is prevalent and increases with age, hypertension, benign prostatic hyperplasia, and antidepressant use.

Context Postmenopausal hormone replacement therapy (HRT) use is common in the United States. Some research suggests that estrogen may have detrimental effects on the tear film and could influence the development of dry eye syndrome, but few data are available on this relationship.

Objective To determine the relationship of HRT and dry eye syndrome.

Design, Setting, and Participants The Women's Health Study, a large cohort study in which 25 665 postmenopausal women provided information about use of HRT at baseline (1992), 12, and 36 months and dry eye syndrome at 48 months.

Main Outcome Measures (1) Clinically diagnosed dry eye syndrome, as reported by participants; (2) severe symptoms (both ocular dryness and irritation either constantly or often); and (3) either clinically diagnosed dry eye syndrome or severe symptoms, compared between women who used HRT vs those who did not.

Results For the combined end point of either clinically diagnosed dry eye syndrome or severe symptoms, the multivariable-adjusted odds ratios were 1.69 (95% confidence interval [CI], 1.49-1.91) for estrogen use alone and 1.29 (95% CI, 1.13-1.48) for estrogen plus progesterone/progestin use compared with no HRT use. Each 3-year increase in the duration of HRT use was associated with a significant 15% (95% CI, 11%-19%) elevation in risk of clinically diagnosed dry eye syndrome or severe symptoms. Results were similar for the combined end point of clinically diagnosed dry eye syndrome and severe symptoms.

Conclusions These data suggest that women who use HRT, particularly estrogen alone, are at increased risk of dry eye syndrome. Physicians caring for women who are taking or considering HRT should be apprised of this potential complication.

Context Low-level lead exposure may increase the risk for a number of chronic age-related diseases. Several studies have documented the presence of lead in lenses with cataract. The intrusion of lead into the lens may alter lens redox status and cause protein conformational changes that decrease lens transparency.

Objective To determine the relationship of cumulative lead exposure with the development of cataract.

Design, Setting, and Participants Tibial (cortical) and patellar (trabecular) bone lead levels were measured by K x-ray fluorescence between 1991 and 1999 in a subset of participants in the Normative Aging Study (NAS), a Boston-based longitudinal study of aging in men. Among the first 795 NAS participants to have bone lead levels measured, we reviewed eye examination data (collected routinely every 3-5 years) for the period after the bone lead measurements were taken. We limited the population to men aged 60 years and older who had sufficient eye examination information available (n = 642). Blood lead levels were also measured.

Main Outcome Measures Cataract assessment was done while masked to the lead level results. A participant was considered to have cataract if there was documentation for either eye of cataract surgery or a cataract graded clinically as 3+ or higher on a 4-point scale. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated as estimates of the magnitude and significance of the relationship of lead exposure with cataract, in logistic regression models.

Results The mean age of the study participants was 69 years and cataract was identified in 122 men. The age-adjusted OR (95% CI) for cataract for men in the highest vs lowest quintile of tibia lead level was 2.68 (1.31-5.50). Further adjustment for pack-years of cigarette smoking, diabetes, blood lead levels, and intake of vitamin C, vitamin E, and carotenoids resulted in an OR of 3.19 (95% CI, 1.48-6.90). For patella lead level, there was an increased risk of cataract in the highest vs lowest quintile (OR, 1.88; 95% CI, 0.88-4.02), but the trend was not significant (P = .16). Blood lead levels, more indicative of short-term exposure levels, were not significantly associated with cataract (OR, 0.89; 95% CI, 0.46-1.72; P = .73).

Conclusions These epidemiological data suggest that accumulated lead exposure, such as that commonly experienced by adults in the United States, may be an important unrecognized risk factor for cataract. This research suggests that reduction of lead exposure could help decrease the global burden of cataract.

Background: Dry eye syndrome (DES) is a prevalent ocular condition, but information on risk or protective factors is lacking.

Objective: We aimed to determine the association between dietary intake of n-3 and n-6 fatty acids and their ratio and the presence of DES.

Design: Of the 39,876 female health professionals in the Women's Health Study (WHS), we studied cross-sectionally 32,470 women aged 45 to 84 years who provided information on diet and DES. We assessed intake of fatty acids by a validated food frequency questionnaire, and DES using self-reports of clinically diagnosed cases. Of the sample, 1546 (4.7%) subjects reported a clinical diagnosis of DES. We used logistic regression models to estimate the odds ratios (OR) and 95% confidence intervals (CI) to describe the relationships of fatty acid intake with DES. We analyzed the association between consumption of fish and DES in a similar way. Results: After adjusting for demographic factors, hormone therapy, and total fat intake, the OR (CI) for the highest versus lowest fifth of n-3 fatty acids was 0.83 (0.70-0.98), P[trend]=0.05. A higher ratio of n-6/n-3 fatty acid consumption was associated with significantly increased risk of DES, OR (CI) =2.51 (1.13-5.58) for >15/1 versus <4/1 (P[trend]=0.01). In addition, tuna consumption was inversely associated with DES (OR=0.81, CI=0.66-0.99 for 2-4 113 g (4 oz) servings/week, and OR=0.32, CI=0.13-0.79 for 5-6 servings/week versus ≤1 servings/week; P[trend]=0.005).

Conclusion: These results suggest that a higher dietary intake of n-3 fatty acids is associated with a decreased presence of DES in women. These findings are consistent with anecdotal clinical observations and postulated biological mechanisms.

Purpose

To evaluate the impact of dry eye syndrome (DES) on vision-associated quality of life.

Design

Cross-sectional study.

Methods

We identified 450 participants in the Women’s Health Study (WHS) and 240 participants in the Physicians’ Health Study (PHS) and sent a supplementary questionnaire asking how much their everyday activities were limited by symptoms of dry eye and to what degree problems with their eyes limited them in reading, driving, working at the computer, their professional activity, and watching TV. By design, one-third of study subjects had clinically diagnosed DES or severe symptoms and two-thirds did not. We used logistic regression to examine relationships of DES with reported problems with everyday activities in each cohort and pooled estimates using meta-analysis methods.

Results

Of the participants invited, 85% completed the supplementary questionnaire, including 135 WHS and 55 PHS participants with DES, and 250 WHS and 149 PHS participants without DES. Controlling for age, diabetes, hypertension and other factors, those with DES were more likely to report problems with reading (OR=3.64, 95% CI 2.45–5.40, P< 0.0001); carrying out professional work (OR=3.49, 95% CI 1.72–7.09, P= 0.001); using a computer (OR=3.37, 95% CI 2.11–5.38, P< 0.0001); TV watching (OR=2.84, 95% CI 1.05–7.74, P=0.04); driving during the day (OR=2.80, 95% CI 1.58–4.96, P< 0.0001); and driving at night (OR=2.20, 95% CI 1.48–3.28, P<0.0001).

Conclusions

DES is associated with a measurable adverse impact on several common and important tasks of daily living, further implicating this condition as an important public health problem deserving increased attention and resources.

Objective To study the efficacy of topical application of alpha-linolenic acid (ALA) and linoleic acid (LA) for dry eye treatment.

Methods Formulations containing ALA, LA, combined ALA and LA, or vehicle alone, were applied to dry eyes induced in mice. Corneal fluorescein staining and the number and maturation of corneal CD11b+ cells were determined by a masked observer in the different treatment groups. Real-time polymerase chain reaction was used to quantify expression of inflammatory cytokines in the cornea and conjunctiva.

Results Dry eye induction significantly increased corneal fluorescein staining; CD11b+ cell number and major histocompatibility complex Class II expression; corneal IL-1α and tumor necrosis factor α (TNF-α) expression; and conjunctival IL-1α, TNF-α, interferon γ, IL-2, IL-6, and IL-10 expression. Treatment with ALA significantly decreased corneal fluorescein staining compared with both vehicle and untreated controls. Additionally, ALA treatment was associated with a significant decrease in CD11b+ cell number, expression of corneal IL-1α and TNF-α, and conjunctival TNF-α.

Conclusions Topical ALA treatment led to a significant decrease in dry eye signs and inflammatory changes at both cellular and molecular levels.

Clinical Relevance Topical application of ALA omega-3 fatty acid may be a novel therapy to treat the clinical signs and inflammatory changes accompanying dry eye syndrome.

Objective To study the effect of topical application of very late antigen 4 (VLA-4) small-molecule antagonist (anti–VLA-4 sm) in a mouse model of dry eye disease.

Methods Anti–VLA-4 sm (or control vehicle) was applied topically to mice placed in a controlled-environment chamber. Corneal fluorescein staining and conjunctival T-cell enumeration were performed in the different treatment groups. Real-time polymerase chain reaction was used to quantify expression of inflammatory cytokines in the cornea and conjunctiva.

Results Dry eye syndrome induced increased corneal fluorescein staining, corneal and conjunctival tumor necrosis factor α messenger RNA expression, and T-cell infiltration into the conjunctiva. Very late antigen 4 blockade significantly decreased corneal fluorescein staining compared with the untreated dry eye disease and control vehicle–treated groups (P < .001 and P = .02, respectively). In addition, VLA-4 blockade was associated with a significant decrease in conjunctival T-cell numbers (P < .001 vs control vehicle–treated group) and tumor necrosis factor-α transcript levels in the cornea (P = .04 vs control vehicle–treated group) and conjunctiva (P = .048 vs control vehicle–treated group).

Conclusion Application of topical anti–VLA-4 sm led to a significant decrease in dry eye signs and suppression of inflammatory changes at the cellular and molecular levels.

Clinical Relevance Topical blockade of VLA-4 may be a novel therapeutic approach to treat the clinical signs and inflammatory changes accompanying dry eye disease.