A genome-wide association study identifies variants in KCNIP4 associated with ACE inhibitor-induced cough.

The most common side effect of angiotensin-converting enzyme inhibitor (ACEi) drugs is cough. We conducted a genome-wide association study (GWAS) of ACEi-induced cough among 7080 subjects of diverse ancestries in the Electronic Medical Records and Genomics (eMERGE) network. Cases were subjects diagnosed with ACEi-induced cough. Controls were subjects with at least 6 months of ACEi use and no cough. A GWAS (1595 cases and 5485 controls) identified associations on chromosome 4 in an intron of KCNIP4. The strongest association was at rs145489027 (minor allele frequency=0.33, odds ratio (OR)=1.3 (95% confidence interval (CI): 1.2-1.4), P=1.0 × 10(-8)). Replication for six single-nucleotide polymorphisms (SNPs) in KCNIP4 was tested in a second eMERGE population (n=926) and in the Genetics of Diabetes Audit and Research in Tayside, Scotland (GoDARTS) cohort (n=4309). Replication was observed at rs7675300 (OR=1.32 (1.01-1.70), P=0.04) in eMERGE and at rs16870989 and rs1495509 (OR=1.15 (1.01-1.30), P=0.03 for both) in GoDARTS. The combined association at rs1495509 was significant (OR=1.23 (1.15-1.32), P=1.9 × 10(-9)). These results indicate that SNPs in KCNIP4 may modulate ACEi-induced cough risk.

Genetic variation in the HLA region is associated with susceptibility to herpes zoster.

Herpes zoster, commonly referred to as shingles, is caused by the varicella zoster virus (VZV). VZV initially manifests as chicken pox, most commonly in childhood, can remain asymptomatically latent in nerve tissues for many years and often re-emerges as shingles. Although reactivation may be related to immune suppression, aging and female sex, most inter-individual variability in re-emergence risk has not been explained to date. We performed a genome-wide association analyses in 22,981 participants (2280 shingles cases) from the electronic Medical Records and Genomics Network. Using Cox survival and logistic regression, we identified a genomic region in the combined and European ancestry groups that has an age of onset effect reaching genome-wide significance (P>1.0 × 10(-8)). This region tags the non-coding gene HCP5 (HLA Complex P5) in the major histocompatibility complex. This gene is an endogenous retrovirus and likely influences viral activity through regulatory functions. Variants in this genetic region are known to be associated with delay in development of AIDS in people infected by HIV. Our study provides further suggestion that this region may have a critical role in viral suppression and could potentially harbor a clinically actionable variant for the shingles vaccine.

Academic clinician frontline-worker wellbeing and resilience during the COVID-19 pandemic experience: Were there gender differences?

Prior research suggests COVID-19 has amplified stress on Academic Clinician Frontline-Workers (ACFW). The aim of this paper is: (1) to better understand the experiences of ACFW during the COVID-19 pandemic including their mental-emotional wellbeing, academic productivity, clinical experiences, and (2) to examine any gender differences. A cross-sectional survey was administered to University of Minnesota/M Health Fairview systems' faculty February-June 2021. Of the 291 respondents, 156 were clinicians, with 91 (58 %) identifying as Frontline-Workers (ACFW). Faculty wellbeing was assessed using validated measures in addition to measures of productivity and sociodemographics. For example, ACFW reported a higher Work-Family Conflict (WFC) scores compared to non-ACFW (26.5 vs. 24.1, p = 0.057) but did not report higher Family-Work Conflict (FWC) scores (17.7 vs. 16.3, p = 0.302). Gender sub-analyses, revealed that women ACFW compared to men ACFW reported higher WFC scores (27.7 vs. 24.1, p = 0.021) and FWC (19.3 vs. 14.3, p = 0.004). Academically, ACFW reported submitting fewer grants and anticipated delays in promotion and tenure due to the COVID-19 (p = 0.035). Results suggest COVID-19 has exacerbated ACFW stress and gender inequities. Reports of anticipated delay in promotion for ACFW may pose a challenge for the long-term academic success of ACFW, especially women ACFW. In addition, women may experience higher FWC and WFC as compared to men. Schools of academic medicine should consider re-evaluating promotion/tenure processes and creating resources to support women ACFW as well as ACFW caregivers.

Intake of meat, meat mutagens, and iron and the risk of breast cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

BACKGROUND: Epidemiological evidence on meat intake and breast cancer is inconsistent, with little research on potentially carcinogenic meat-related exposures. We investigated meat subtypes, cooking practices, meat mutagens, iron, and subsequent breast cancer risk. METHODS: Among 52 158 women (aged 55-74 years) in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, who completed a food frequency questionnaire, 1205 invasive breast cancer cases were identified. We estimated meat mutagen and haem iron intake with databases accounting for cooking practices. Using Cox proportional hazards regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) within quintiles of intake. RESULTS: Comparing the fifth to the first quintile, red meat (HR=1.23; 95% CI=1.00-1.51, P trend=0.22), the heterocyclic amine (HCA), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), (HR=1.26; 95% CI=1.03-1.55; P trend=0.12), and dietary iron (HR=1.25; 95% CI=1.02-1.52; P trend=0.03) were positively associated with breast cancer. We observed elevated, though not statistically significant, risks with processed meat, the HCA 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), mutagenic activity, iron from meat, and haem iron from meat. CONCLUSION: In this prospective study, red meat, MeIQx, and dietary iron elevated the risk of invasive breast cancer, but there was no linear trend in the association except for dietary iron.

Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network.

Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of "precision medicine." The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

Impact of unilateral and bilateral vision loss on quality of life.

AIM: To investigate whether unilateral vision loss reduced any aspects of quality of life in comparison with normal vision and to compare its impact with that of bilateral vision loss. METHODS: This study used cluster stratified random sample of 3271 urban participants recruited between 1992 and 1994 for the Melbourne Visual Impairment Project. All predictors and outcomes were from the 5 year follow up examinations conducted in 1997-9. RESULTS: There were 2530 participants who attended the follow up survey and had measurement of presenting visual acuity. Both unilateral and bilateral vision loss were significantly associated with increased odds of having problems in visual functions including reading the telephone book, newspaper, watching television, and seeing faces. Non-correctable by refraction unilateral vision loss increased the odds of falling when away from home (OR = 2.86, 95% CI 1.16 to 7.08), getting help with chores (OR = 3.09, 95% CI 1.40 to 6.83), and becoming dependent (getting help with meals and chores) (OR = 7.50, 95% CI 1.97 to 28.6). Non-correctable bilateral visual loss was associated with many activities of daily living except falling. CONCLUSIONS: Non-correctable unilateral vision loss was associated with issues of safety and independent living while non-correctable bilateral vision loss was associated with nursing home placement, emotional wellbeing, use of community services, and activities of daily living. Correctable or treatable vision loss should be detected and attended to.

Effect of hoof angle on joint contact area in the equine metacarpophalangeal joint following simulated impact loading ex vivo.

REASONS FOR PERFORMING STUDY: To add to the existing data on impact loading of the metacarpophalangeal (MCP) joint as a precursor to assessing the potential role of impact in joint disease. OBJECTIVES: To examine the effect of impact loading on contact areas of the first phalanx (P1) and proximal sesamoids (PS) with the third metacarpal (McIII) under 3 hoof-strike conditions (toe-first, flat, heel-first). STUDY DESIGN: Randomised, repeated controlled experiment using cadaver material. METHODS: Eight cadaver limbs were subjected to randomised, repeated controlled trials where the hoof was struck by a pendulum impact machine (impact velocity 3.55 m/s) under 3 strike conditions. Data from pressure sensitive film placed over medial and lateral McIII condyles and lateromedially across the dorsal aspect of McIII were quantified: total areas of P1 and PS contact (cm(2) ) at maximum recorded pressure; centroid locations of contact areas relative to the sagittal ridge (cm) and transverse ridge (cm) and dispersion of pixels (cm(4) ) for each McIII condyle (medial/lateral). The effect of the strike conditions on each variable were statistically tested using repeated-measures ANOVA (α = 0.05). RESULTS: Contact area between P1 and McIII condyles fell in well-defined areas bounded by the sagittal and transverse ridge, contact areas from PS were smaller and widely dispersed across McIII palmar border. Ratio of contact area of P1 to PS was 2.83 (P<0001). Hoof strike had no significant effect on contact area (P>0.54) CONCLUSIONS: Contact at impact (primarily from P1 and distally situated on McIII), contrasts with contact areas at midstance from both P1 and PS, symmetrically placed. Under impact, the greatest contact area was on the dorsal aspect of the medial condyle and coincides with the area subjected to the greatest increase in subchondral bone stiffening in joint disease.

Effect of hoof orientation and ballast on acceleration and vibration in the hoof and distal forelimb following simulated impacts ex vivo.

REASONS FOR PERFORMING STUDY: We wished to add to the existing baseline data on impact loading of the distal limb as a precursor to assessing the potential role of impact in injury and joint disease. OBJECTIVES: To examine the effect of 3 hoof-strike conditions (toe first, flat and heel first) and 2 specimen masses (with and without a ballast of ∼2% body mass) on impact deceleration and vibration frequencies and energies at the hoof, first phalanx and third metacarpal. STUDY DESIGN: Biomechanical experiments in cadaver material. METHODS: Eight cadaver limbs were subjected to randomised, repeated controlled trials, in which the hoof was struck by a pendulum impact-testing machine (impact velocity, 3.55 m/s) in the 3 strike and 2 mass conditions. Data from triaxial accelerometers on the hoof, first phalanx and third metacarpal quantified, for all trials, the peak impact acceleration, frequencies in the first 6.4 ms following impact, the frequency with the most energy, 95% of the total energy and the frequency at 95% cumulative energy. The effects of the strike and mass conditions on each variable were statistically tested using repeated-measures ANOVA (α = 0.05). RESULTS: Signal energy reaching the third metacarpal was 6-31% of that at the hoof. A heel-first strike produced the largest peak accelerations and highest frequencies among all strike conditions, and changing the mass had no effect regardless of strike condition. CONCLUSIONS: Large accelerations that occur upon impact of the hoof with the ground are attenuated by the distal structures of the equine limb, but still carry considerable energy within the signal that could be damaging to tissue and are dependent on hoof-strike condition but not ballast. Our results suggest that impact loading on the hoof could be a factor in contributing to bone injury and joint disease in the distal limb.

Attributable risk estimates for cataract to prioritize medical and public health action.

PURPOSE: Cataract is the most common cause of blindness in the world. The purpose of this study was to estimate the population attributable risk associated with identified risk factors for cortical, nuclear, and posterior subcapsular (PSC) cataract in a representative sample of the Victorian population aged 40 years and older. METHODS: Cluster, stratified sampling was used and participants were recruited through a household census. At locally established test sites, standardized clinical examinations were performed to assess cataract and personal interviews were conducted to quantify potential risk factors. Multivariate logistic regression was used to determine the independent risk factors associated with the three types of cataract, and the population attributable risk was calculated. RESULTS: A total of 3271 (83% of eligible) of the urban residents and 1473 (92%) rural residents participated. The urban residents ranged in age from 40 to 98 years (mean, 59 years), and 1511 (46%) were men. The rural residents ranged in age from 40 to 103 years (mean, 60 years), and 701 (48%) were men. The overall prevalence of cortical cataract was 12.1% (95% CL 10.5, 13.8), nuclear cataract 12.6% (95% CL 9.61, 15.7), and PSC cataract 4.93% (95% CL 3.68, 6.17). Significant risk factors for cortical cataract included age, female gender, diabetes for greater than 5 years, gout for greater than 20 years, arthritis, myopia, average annual ocular UV-B exposure, and family history of cataract (parents or siblings). Significant risk factors for nuclear cataract included age, female gender, rural residence, age-related maculopathy, diabetes for greater than 5 years, smoker for greater than 30 years, and myopia. The significant risk factors for PSC cataract were age, rural residence, thiazide diuretic use, and myopia. Of the modifiable risk factors, ocular UV-B exposure explains 10% of the cortical cataract in the community, and cigarette smoking accounts for 17% of the nuclear cataract. CONCLUSIONS: Because of the near universal exposure to UV-B in the environment, ocular protection has one of the highest modifiable attributable risks for cortical cataract and would therefore be an ideal target for public health intervention. Quit smoking campaigns can be expanded to incorporate information about the excess cataract in the community associated with long-term smoking. Nonmodifiable risk factors such as age, gender, and long-term medication use have implications for the timely referral and treatment for those at higher risk of cataract.

Refractive errors in an urban population in Southern India: the Andhra Pradesh Eye Disease Study.

PURPOSE: To assess the prevalence, distribution, and demographic associations of refractive error in an urban population in southern India. METHODS: Two thousand five hundred twenty-two subjects of all ages, representative of the Hyderabad population, were examined in the population-based Andhra Pradesh Eye Disease Study. Objective and subjective refraction was attempted on subjects >15 years of age with presenting distance and/or near visual acuity worse than 20/20 in either eye. Refraction under cycloplegia was attempted on all subjects < or =15 years of age. Spherical equivalent >0.50 D in the worse eye was considered as refractive error. Data on objective refraction under cycloplegia were analyzed for subjects < or =15 years and on subjective refraction were analyzed for subjects >15 years of age. RESULTS: Data on refractive error were available for 2,321 (92.0%) subjects. In subjects < or =15 years of age, age-gender-adjusted prevalence of myopia was 4.44% (95% confidence interval [CI], 2.14%-6.75%), which was higher in those 10 to 15 years of age (odds ratio, 2.75; 95% CI, 1.25-6.02), of hyperopia 59.37% (95% CI, 44.65%-74.09%), and of astigmatism 6.93% (95% CI, 4.90%-8.97%). In subjects >15 years of age, age-gender-adjusted prevalence of myopia was 19.39% (95% CI, 16.54%-22.24%), of hyperopia 9.83% (95% CI, 6.21%-13.45%), and of astigmatism 12.94% (95% CI, 10.80%-15.07%). With multivariate analysis, myopia was significantly higher in subjects with Lens Opacity Classification System HI nuclear cataract grade > or =3.5 (odds ratio, 9.10; 95% CI, 5.15-16.09), and in subjects with education of class 11 or higher (odds ratio, 1.80; 95% CI, 1.18-2.74); hyperopia was significantly higher in subjects > or =30 years of age compared with those 16 to 29 years of age (odds ratio, 37.26; 95% CI, 11.84-117.19), in females (odds ratio, 1.86; 95% CI, 1.33-2.61), and in subjects belonging to middle and upper socioeconomic strata (odds ratio, 2.10; 95% CI, 1.09-4.03); and astigmatism was significantly higher in subjects > or =40 years of age (odds ratio, 3.00; 95% CI, 2.23- 4.03) and in those with education of college level or higher (odds ratio, 1.73; 95% CI, 1.07-2.81). CONCLUSIONS: These population-based data on distribution and demographic associations of refractive error could enable planning of eye-care services to reduce visual impairment caused by refractive error. If these data are extrapolated to the 255 million urban population of India, among those >15 years of age an estimated 30 million people would have myopia, 15.2 million hyperopia, and 4.1 million astigmatism not concurrent with myopia or hyperopia; in addition, based on refraction under cycloplegia, 4.4 million children would have myopia and 2.5 million astigmatism not concurrent with myopia or hyperopia.

Blindness in the Indian state of Andhra Pradesh.

PURPOSE: To determine the current prevalence and causes of blindness in the Indian state of Andhra Pradesh to assess if blindness has decreased since the last survey of 1986-1989. METHODS: A population-based epidemiology study, using a stratified, random, cluster, systematic sampling strategy, was conducted in the state of Andhra Pradesh in India. Participants of all ages (n = 10,293), 87.3% of the 11,786 eligible, from 94 clusters in one urban and three rural areas representative of the population of Andhra Pradesh, underwent interview and a detailed dilated ocular evaluation by trained professionals. Blindness was defined as presenting distance visual acuity < 6/60 or central visual field < 20(o) in the better eye. RESULTS: Two hundred seventy-five participants were blind, a prevalence of 1.84% (95% confidence interval, 1.49%-2.19%) when adjusted for the age, sex, and urban-rural distribution of the population in 2000. The causes of this blindness were easily treatable in 60.3% (cataract, 44%; refractive error, 16.3%). Preventable corneal disease, glaucoma, complications of cataract surgery, and amblyopia caused another 19% of the blindness. Blindness was more likely with increasing age and decreasing socioeconomic status, and in female subjects and in rural areas. Among the 76 million population of Andhra Pradesh, 714,400 are estimated to have cataract-related blindness (615,600 cataract, 53,200 cataract surgery-related complications, 45,600 aphakia), and 228,000 refractive error-related blindness (159,600 myopia, 22,800 hyperopia, 45,600 refractive error-related amblyopia). If 95% of the cataract and refractive error blindness in Andhra Pradesh had been treated effectively, 3.4 and 7.4 million blind-person-years, respectively, could have been prevented. If 90% of the blindness due to preventable corneal disease and glaucoma had been prevented, another 2.7 million blind-person-years could have been prevented. CONCLUSIONS: The prevalence of blindness in this Indian state has increased from 1.5% in the late 1980s to 1.84% currently, as against the target of the National Program for Control of Blindness to reduce the prevalence to 0.3% by 2000. The number of people with cataract-related blindness has not reduced even with the eye care policy focus on cataract. Reduction of blindness in India will require strategies that are more effective than those that have been pursued so far.

Prevalence and risk factors of myopia in Victoria, Australia.

OBJECTIVE: To determine the prevalence and risk factors of myopia in urban and rural Victoria, Australia. PARTICIPANTS AND METHODS: The Visual Impairment Project is a population-based prevalence study of eye disease in which both urban and rural adult populations were examined. Refractive data on the participants were collected using logMAR visual acuity, corrective lens measurement, and subjective refraction. All refractive error data were converted into spherical equivalent and myopia was defined at 2 levels: worse than -0.5 diopters (D) and worse than -1.00 D. RESULTS: A total of 3271 (83%) urban and 1473 (91%) rural residents were examined. The overall prevalence of myopia worse than -0.50 D in the population was 17% (95% confidence limit = 15.8%, 18.0%). Prevalence of myopia decreased from 24% in those aged 40 to 49 years to 12% in those aged 70 to 79 years, and then increased to 17% in people older than 80 years. The younger age groups also had higher usage of myopic corrective lenses throughout their lives than the older age groups, indicating an increased use of myopic corrective lenses in recent times. Myopia was found to be significantly higher in people with higher education levels (chi2 = 119.20, P < .001), in clerks and professionals (chi2 = 132.53, P < .001), in people born in southeast Asia (chi2 = 77.62, P < .001), and in people with higher degrees of nuclear opacity (chi2 = 55.26, P < .001). CONCLUSION: Myopia rates in the Visual Impairment Project generally decrease with age and use of myopic correction has increased in recent times. Myopia was significantly related to education level, occupation, country of birth, and nuclear opacity.

Predictability of excimer laser treatment of myopia. Melbourne Excimer Laser Group.

OBJECTIVE: To prospectively examine the predictability of excimer laser photorefractive keratectomy and photoastigmatic refractive keratectomy for myopia that ranged from -1 to -18 diopters (D). METHODS: Patients were treated with an excimer laser and followed up prospectively for 12 months. Low myopia was treated in one ablation zone (6.0 mm), high myopia in two ablation zones (5.0 and 6.0 mm), and extreme myopia in three ablation zones (4.5, 5.0, and 6.0 mm) with a maximum treatment of 15 D. Data were analyzed to determine the distribution of the various postoperative outcomes by preoperative myopia. RESULTS: Two hundred seventy-four low myopes, 189 high myopes, and 41 extreme myopes were available for 12-month follow-up. The re-treatment rate increased with preoperative myopia. The predictability of refraction and uncorrected and best corrected visual acuity progressively decreased with increasing myopia. The likelihood of losing lines of best corrected visual acuity and corneal haze increased with increasing myopia. CONCLUSION: These data should help in the counseling of patients about the likely outcome if they have excimer laser surgery to correct myopia.

Overcorrection after excimer laser treatment of myopia and myopic astigmatism. Melbourne Excimer Laser Group.

OBJECTIVE: To study the incidence and associations of overcorrection after excimer laser treatment of myopia and myopic astigmatism. METHODS: The study cohort consisted of 645 patients who had photorefractive or photoastigmatic refractive keratectomy done by an excimer laser during a 2-year period. Patients were assessed 1,3,6, and 12 months postoperatively. The variables evaluated were visual acuity, refraction, keratometry, and corneal clarity. RESULTS: At 1 month, overcorrection of more than +1 diopter spherical equivalent (SEQ) was seen in 22% of the eyes. This progressively regressed so that only 8.6% of the 140 eyes that were overcorrected at 1 month were overcorrected at 1 year. Overall, 2.2% of eyes were overcorrected at 1 year. The magnitude of attempted correction and use of topical nonsteroidal anti-inflammatory drugs disclosed a notable association with occurrence of overcorrection at 1, 3, and 6 months. The use of bandage contact lenses also was associated with overcorrection at 1 and 3 months. After controlling for myopia and use of contact lenses, the odds of overcorrection for use of topical nonsteroidal anti-inflammatory drugs at 1,3, and 6 months were 2.21 (95% confidence limits [CL]=1.49, 3.44), 1.69 (95% CL=0.88, 3.24), and 2.01 (95% CL=0.88, 4.56), respectively. The odds of overcorrection with bandage contact lenses were 1.79 (95% CL=1.05, 3.05) at 1 month and 2.42 (95% CL=1.23, 4.75) at the end of 3 months. No associations were seen between overcorrection and age, gender, surgical technique, or simultaneous astigmatic corrections. CONCLUSIONS: Overcorrection is common during the early postlaser treatment period and is associated with degree of myopia, use of nonsteroidal anti-inflammatory drugs, and bandage contact lens wear.

Age-specific causes of bilateral visual impairment.

OBJECTIVES: To describe the age-specific prevalence of common eye diseases causing bilateral visual impairment and estimate the total number of Australians with cause-specific visual impairment. METHODS: Cluster-stratified random sample of 5147 residents aged 40 years and older from urban and rural areas and aged-care facilities. Participants completed a standardized interview and eye examination. Four levels of bilateral visual impairment were defined: less than 20/40 to 20/60 and/or homonymous hemianopia (mild), less than 20/60 to 20/200 or better and/or less than 20 degrees to 10 degrees radius field (moderate), less than 20/200 to 10/200 and/or less than 10 degrees to 5 degrees radius field (severe), and less than 1O/ 200 and/or less than 50 radius field (profound). The major cause of vision loss was identified for all participants found to be visually impaired. RESULTS: Uncorrected refractive error was the most common cause of bilateral visual impairment across all decades of life, rising from 0.5% in 40- to 49-year-olds to 13% among those aged 80 years and older. Prevalence of visual impairment due to diabetic retinopathy was 0.7% in 50- to 59-year-olds and 0.8% in those older than 80 years. Visual impairment due to glaucoma had a prevalence of 0.7% among 60-year-olds and rose to 4% of those older than 90 years. The prevalence of visual impairment due to cataract (only present in those aged 70 years or older) rose from 0.6% to 11% in those older than 90 years, and the prevalence of visual impairment due to age-related macular degeneration rose from 0.8% to 16% in those older than 90 years. CONCLUSIONS: The predominant causes of visual impairment change with age. Recognition of these patterns is fundamental for early diagnosis and treatment of eye disease and, where appropriate, referral for rehabilitation.

Association of demographic, familial, medical, and ocular factors with intraocular pressure.

OBJECTIVE: To describe the distribution and associations of demographic, familial, medical, and ocular factors with intraocular pressure (IOP). METHODS: A cluster stratified random sample of urban and rural residents of Victoria, Australia, aged 40 years and older. Participants completed an interview and underwent a standardized dilated ophthalmic examination including measurement of IOP with an electronic applanation tonometer (Tono-Pen). Glaucoma status (possible, probable, definite) was determined by a consensus panel. The main outcome measure was IOP. RESULTS: The mean age of the 4576 participants was 59 years, 53% were women, 32% were born overseas, and 132 had open-angle glaucoma. Geometric mean (SD) IOP was 14.3 (+/-1.5) mm Hg. The relationship between IOP and nuclear sclerosis, iris color, and family history of glaucoma depended on glaucoma status. In those with glaucoma, family history of glaucoma and country of birth were significantly associated with IOP in multivariate models (model: r(2) = 0.08, P =.01). In the group without glaucoma, place of residence, use of alcohol, iris color, vitamin E intake, and spherical equivalent were associated with IOP (model: r(2) = 0.01, P =.006). CONCLUSION: In participants with glaucoma, genetic factors seem to be stronger predictors of IOP, whereas in those without glaucoma, lifestyle and physiological factors seem to play a greater role.

Risk factors for age-related maculopathy: the Visual Impairment Project.

OBJECTIVE: To describe the risk factors and associated population attributable risk for age-related maculopathy (ARM) and age-related macular degeneration (AMD) in Australians aged 40 years and older. METHODS: Residents were recruited from 9 randomly selected urban clusters and 4 randomly selected rural clusters in Victoria, Australia. At locally established test sites, the following information was collected: visual acuity, medical and health history, lifetime sunlight exposure, dietary intake, and fundus photographs. Age-related maculopathy and AMD were graded from the fundus photographs using an international classification and grading system. Backwards logistic regression was used to identify the independent risk factors for ARM and AMD. RESULTS: The participation rate was 83% (n = 3271) among the urban residents and 92% (n = 1473) among the rural residents. Gradable fundus photographs of either eye were available for 4345 (92%) of the 4744 participants. There were 656 cases of ARM, giving a weighted prevalence of 15.1% (95% confidence limit [CL], 13.8, 16.4); and there were 30 cases of AMD, giving a weighted prevalence of 0.69% (95% CL, 0.33, 1.03). In multiple logistic regression, the risk factors for AMD were as follows: age (odds ratio [OR], 1.23; 95% CL, 1.17, 1.29), smoked cigarettes for longer than 40 years (OR, 2.39; 95% CL, 1.02, 5.57), and ever taken angiotensin-converting enzyme inhibitors (OR, 3.26; 95% CL, 1.33, 8.01). The magnitude of all of these risk factors was slightly less for ARM, and having ever taken blood cholesterol-lowering medications was also significant (OR, 1.67; 95% CL, 1.12, 2.47; P =.001). CONCLUSION: Smoking is the only modifiable risk factor for ARM and AMD, among the many environmental and systemic factors that were assessed.

Pseudoexfoliation syndrome in Australian adults.

PURPOSE: To describe the prevalence and correlates of pseudoexfoliation syndrome in Australians aged 40 years and older. METHODS: Cluster, stratified sampling was employed to identify a cohort representative of the population of the state of Victoria aged 40 years and older that included urban, rural, and nursing home residents. A standardized personal interview and clinical eye examination, including intraocular pressure, were performed at locally established test sites. The presence of any pseudoexfoliation material on the iris or lens capsule was noted on dilated slit-lamp examination. Participants were classified as having pseudoexfoliation syndrome if any pseudoexfoliation material was present in either eye. Univariate analyses with t tests and chi-square were first employed to evaluate risk factors for pseudoexfoliation. Any factors with P <.10 were then fitted in a backward stepwise logistic regression model. For the final multivariate models, P <.05 was considered statistically significant. RESULTS: A total of 3,271 of the urban residents (83% of eligible), 403 nursing home residents (90% of eligible), and 1473 rural residents (92%) participated. The urban residents ranged in age from 40 to 98 years (mean = 59), and 1,511 (46%) were men. The nursing home residents ranged in age from 46 to 101 years (mean 82), and 85 (21%) were men. The rural residents ranged in age from 40 to 103 years (mean 60), and 701 (47.5%) were men. Participants with bilateral cataract extraction were excluded from further analyses. The overall rate of pseudoexfoliation syndrome in this population was 0.98% (95% confidence limit = 0.57, 1.28). The prevalence of pseudoexfoliation material in either eye increased significantly with age. No cases of pseudoexfoliation syndrome were observed in people aged 90 years and older. However, people with bilateral cataract surgery had been excluded from these analyses. After adjusting for age and cataract, only glaucoma remained significantly related to pseudoexfoliation (odds ratio = 3.80, 95% confidence limit = 1.73, 8.33). DISCUSSION: In conclusion, we found only two strong correlates of pseudoexfoliation in our population-based sample of Victorians aged 40 years and older: age and glaucoma.

Comparison of results of excimer laser correction of all degrees of myopia at 12 months postoperatively. The Melbourne Excimer Laser Group.

UNLABELLED: To examine prospectively the efficacy and safety of photorefractive keratectomy and photoastigmatic refractive keratectomy. METHODS: We treated 645 eyes (440 patients) with a VisX Twenty/Twenty excimer laser and followed them up for 12 months. RESULTS: The percentage of eyes with myopia between -5.01 and -10.00 diopters spherical equivalent within 1 and 2 diopters of emmetropia at 12 months was 65% (123 of 189) and 90% (170 of 189), respectively, whereas the corresponding percentages for eyes with myopia greater than -10.00 diopters spherical equivalent were 39% (16 of 41) and 56% (23 of 41), and for eyes with myopia of -5.00 diopters spherical equivalent or less, 87% (238 of 273) and 99% (270 of 273), respectively. Uncorrected visual acuity of 20/20 and 20/40 or better at 12 months was attained in 47% (129 of 273) and 87% (237 of 273) of the eyes with myopia -5.00 diopters spherical equivalent or less, respectively. At 12 months, 48 (25%) of the 189 eyes with myopia between -5.01 and -10.00 diopters spherical equivalent had uncorrected visual acuity of 6/6 or better and 135 (71%), 6/12. At 12 months, one eye (2%) with myopia greater than -10.00 diopters spherical equivalent had uncorrected visual acuity of 6/6 and 11 (27%) of 41 eyes, 6/12. Ten (4%) of the 273 eyes with myopia of -5.00 diopters spherical equivalent or less, 15 (8%) of the 189 eyes with myopia between -5.01 and -10.00 diopters spherical equivalent, and nine (22%) of the 41 eyes with myopia greater than -10.00 diopters spherical equivalent had lost two or more LogMAR lines of best-corrected visual acuity at 12 months. CONCLUSION: Excimer laser surgery is highly reliable for myopia of -5.00 diopters spherical equivalent or less and is less reliable for greater myopia.

Undercorrection after excimer laser refractive surgery. Excimer Laser Group.

PURPOSE: The incidence and correlations of undercorrection were studied for 1 year after excimer laser surgery for myopia or myuopic astigmatism. METHODS: A consecutive series of 645 eyes of 440 patients were studied. Eyes were examined preoperatively and at 1, 3, 6, and 12 months after surgery. The parameters evaluated were visual acuity, refraction, and corneal clarity. RESULTS: Following excimer laser surgery, undercorrection of > or = -1.00 diopters gradually increased from 10% at 1 month to 40% at 12 months. Increasing degree of preoperative myopia was significantly associated with increasing occurrence of undercorrection at 3 months (chi 2 = 17.3, P < .001), 6 months (chi 2 = 53.6, P < .001), and 12 months (chi 2 = 64.8, P < .001). Undercorrection was more common in eyes that had had photorefractive keratectomy than in those that had had photoastigmatic refractive keratectomy (odds ratio, 0.40; 95% confidence interval, 0.25 to 0.60). At 1 year, a loss of 2 or more lines of best-corrected visual acuity was recorded in 38% of undercorrected patients. Loss of 2 or more lines of best-corrected visual acuity was more common in patients undercorrected by -1.00 diopter or more (odds ratio, 8.8; 95% confidence interval, 5.4 to 14.6). No relationship was seen between corneal haze and loss of best-corrected visual acuity. Undercorrection was not associated with age, gender, use of nonsteroidal anti-inflammatory drugs, bandage contact lens wear, or corneal haze. Patients with lower degrees of myopia reached a stable refraction more quickly. At 6 months, 71% were within +/- 0.5 diopter of 1-year refraction. Of 17 patients with undercorrection who were treated with topical corticosteroids, only one patient showed a permanent beneficial change. CONCLUSION: Occurrence of undercorrection is more common in patients with severe myopia and when simultaneous astigmatic corrections are undertaken.