Low-concentration atropine eyedrops for myopia control in a multi-racial cohort of Australian children: A randomised clinical trial.

BACKGROUND: To test the hypothesis that 0.01% atropine eyedrops are a safe and effective myopia-control approach in Australian children. METHODS: Children (6-16 years; 49% Europeans, 18% East Asian, 22% South Asian, and 12% other/mixed ancestry) with documented myopia progression were enrolled into this single-centre randomised, parallel, double-masked, placebo-controlled trial and randomised to receive 0.01% atropine (n = 104) or placebo (n = 49) eyedrops (2:1 ratio) instilled nightly over 24 months (mean index age = 12.2 ± 2.5 and 11.2 ± 2.8 years, respectively). Outcome measures were the changes in spherical equivalent (SE) and axial length (AL) from baseline. RESULTS: At 12 months, the mean SE and AL change from baseline were -0.31D (95% confidence interval [CI] = -0.39 to -0.22) and 0.16 mm (95%CI = 0.13-0.20) in the atropine group and -0.53D (95%CI = -0.66 to -0.40) and 0.25 mm (95%CI = 0.20-0.30) in the placebo group (group difference p ≤ 0.01). At 24 months, the mean SE and AL change from baseline was -0.64D (95%CI = -0.73 to -0.56) and 0.34 mm (95%CI = 0.30-0.37) in the atropine group, and -0.78D (95%CI = -0.91 to -0.65) and 0.38 mm (95%CI = 0.33-0.43) in the placebo group. Group difference at 24 months was not statistically significant (p = 0.10). At 24 months, the atropine group had reduced accommodative amplitude and pupillary light response compared to the placebo group. CONCLUSIONS: In Australian children, 0.01% atropine eyedrops were safe, well-tolerated, and had a modest myopia-control effect, although there was an apparent decrease in efficacy between 18 and 24 months, which is likely driven by a higher dropout rate in the placebo group.

Western Australia Atropine for the Treatment of Myopia (WA-ATOM) study: Rationale, methodology and participant baseline characteristics.

IMPORTANCE: Atropine eyedrops are a promising treatment for slowing myopia progression in East Asian children. However, its effects on children in Australia, including those of non-Asian background, have not been well-studied. BACKGROUND: The Western Australia Atropine for the Treatment of Myopia (WA-ATOM) study aims to determine the efficacy and long-term effects of low-dose atropine eyedrops in myopia control. This paper describes the study rationale, methodology and participant baseline characteristics. DESIGN: Single-centre, double-masked, randomized controlled trial. PARTICIPANTS: Children (6-16 years) with spherical equivalent ≤-1.50 D in each eye, astigmatism ≤1.50 D and myopia progression by ≥0.50 D/year. METHODS: Enrolled children were randomly assigned 2:1 to receive 0.01% atropine or placebo eyedrops. Participants are examined every 6 months during first 3 years of the study (2-year treatment phase followed by a 1-year washout phase), and then at a 5-year follow-up (2 years after the end of the washout phase). MAIN OUTCOME MEASURES: Annual progression rate of myopia and axial length, tolerability to eyedrops and incidence and severity of unwanted effects. RESULTS: Out of 311 children who were referred, 242 were suitable for study participation, and 153 were subsequently enrolled. The baseline characteristics of enrolled participants are presented. CONCLUSIONS AND RELEVANCE: Outcomes of the WA-ATOM study will inform on the efficacy, tolerability, safety and long-term effects of low-dose atropine eyedrops in myopia control in Australian children. The impact of ocular sun exposure, iris colour and parental myopia on the efficacy of low-dose atropine will also be assessed.

Health Service Use and Mortality of the Elderly Blind.

PURPOSE: To determine whether blindness in older people is associated with increased health service use and mortality. DESIGN: Retrospective matched cohort study from July 1, 1999, through June 30, 2010. PARTICIPANTS: A blind cohort 65 years of age and older from a volunteer blind register and a cohort of age- and gender-matched controls selected randomly from the Western Australian electoral roll. METHODS: Person-level linked hospital, emergency department (ED), mental health, and death records for the blind and control cohorts were used. Generalized estimating equations assuming a negative binomial distribution were used to estimate relative rates of hospital admissions, lengths of stay, and mortality after adjusting for sociodemographic variables and comorbidity. Emergency department and mental health service visits also were quantified. MAIN OUTCOME MEASURES: Relative rates of hospital admissions, lengths of stay, and mortality, as well as crude proportions of ED and mental health service visits. RESULTS: The blind cohort comprised 1726 individuals alongside 1726 matched controls; 39% were men, and the mean age was 83 years. Combined, the cohorts accumulated a total of 34 130 hospital admissions amounting to 201 867 bed-days. After adjusting for the principal reason for hospital admission and comorbidity, the blind cohort was admitted to the hospital 11% (95% confidence interval [CI], 6%-17%) more often than the control cohort. The blind cohort also stayed in the hospital longer than the controls, but this effect varied by age. Blind participants 65 to 69 years of age spent 88% more days (95% CI, 27%-178%) in the hospital compared with age-matched controls, whereas there was no difference in length of stay between the cohorts by 80 years of age (rate ratio, 1.10; 95% CI, 0.97-1.25). A larger proportion of the blind cohort visited a hospital ED and accessed mental health services compared with the control cohort. CONCLUSIONS: Health service use is increased for the elderly blind compared with age-matched controls after accounting for comorbidity. The elderly blind have more hospital admissions, ED visits, and mental health-related visits. The younger elderly blind stay longer in hospital. However, there was no evidence of worse mortality outcomes after adjusting for comorbidity.

Hospitalization rates of children who are blind.

BACKGROUND: To evaluate the impact of blindness on hospitalization rates of children. DESIGN: Matched cohort study. PARTICIPANTS: Children confirmed as legally blind (2003-2009), age- and gender-matched to control cohort of normally sighted children from the state register of births. METHODS: The rates and reasons for admission to hospital were compared using hospital morbidity records. The association of blindness with rates of admission and length of stay in hospital, 2003-2010, were estimated using multivariate negative binomial regression models. MAIN OUTCOME MEASURES: Descriptive statistics, incident rate ratios, and predicted means for hospital separations and length of stay. RESULTS: Fifty-nine blind and 59 control children had a combined total of 107 separations accounting for 237 bed days in hospital after the index date of legal blindness. The median age at the index date was 8 years. Over 90% of separations and 92% of bed days were incurred by 22 blind children. Blind children had four (95% confidence interval 1.9-9.3) times more hospital separations and stayed in hospital six (95% confidence interval 1.9-17.5) times longer than the control cohort children. There were more than 40 times as many comorbidities recorded by the blind children (n = 201) compared with the control children (n = 5). A third of the blind children were hospitalized for respiratory conditions. CONCLUSIONS: Children who are born or become blind in childhood have more and longer periods in hospital than sighted children likely because of complex comorbid health problems. There was a disproportionate incidence of comorbid respiratory diseases in the blind children.

The epidemiology of eye injuries in Western Australia: a retrospective 10-year study.

CLINICAL RELEVANCE: Eye injuries constitute a significant cause of preventable lifelong visual impairment or blindness. It is important to identify the context in which these injuries occur to develop intervention programs to reduce the incidence and severity of injury. BACKGROUND: To evaluate the nature, external cause, place of occurrence and incidence rate of eye injuries treated at hospitals in Western Australia. METHODS: Retrospective, population-based study of patients presenting to all emergency departments or admitted to hospital with primary or secondary eye injuries between 2005 and 2014. RESULTS: The combined incidence rate of eye injuries requiring tertiary care was 278 per 100 000 person-years (95% CI 276-280). Significantly more males (79%, 44 569) presented to emergency departments (p < 0.001), and most injuries involved the cornea and conjunctiva (83%). The injury incidence rate was 248 per 100 000 person-years (95% CI 246-250). A total of 2823 and 3951 individuals were admitted to hospital for a primary or secondary eye injury, respectively. The most frequent primary diagnosis on admission was contusion (19%). Assault (24%) was the most common cause of injury requiring inpatient treatment. Indigenous individuals were hospitalised for an eye injury at a rate of 109 per 100 000 person-years (95% CI 102-116), compared to 27 (95% CI 26-27) for non-Indigenous individuals. Each year was associated with an increase in the mean number of eye injuries (7% and 5% for emergency department and hospital admission data, respectively). CONCLUSION: Indigenous individuals and males experience eye injuries requiring tertiary management disproportionately. Indigenous female patients were conspicuously affected by eye injuries. Remedial intervention strategies should incorporate violence prevention as assault is a significant cause of eye injury.

Corneal Transplant Follow-up Study II: a randomised trial to determine whether HLA class II matching reduces the risk of allograft rejection in penetrating keratoplasty.

PURPOSE: A randomised trial to test the hypothesis that human leucocyte antigen (HLA) class II matching reduces the risk of allograft rejection in high-risk penetrating keratoplasty (PK). METHODS: All transplants were matched for HLA class I antigens (≤2 mismatches at the A and B loci) and corneas were allocated to patients by cohort minimisation to achieve 0, 1 or 2 HLA class II antigen mismatches. The corneal transplants (n=1133) were followed for 5 years. The primary outcome measure was time to first rejection episode. RESULTS: Cox regression analysis found no influence of HLA class II mismatching on risk of immunological rejection (HR 1.13; 95% CI 0.79 to 1.63; p=0.51). The risk of rejection in recipients older than 60 years was halved compared with recipients ≤40 years (HR 0.51; 95% CI 0.36 to 0.73; p=0.0003). Rejection was also more likely where cataract surgery had been performed after PK (HR 3.68; 95% CI 1.95 to 6.93; p<0.0001). In univariate analyses, preoperative factors including chronic glaucoma (p=0.02), vascularisation (p=0.01), inflammation (p=0.03), ocular surface disease (p=0.0007) and regrafts (p<0.001) all increased the risk of rejection. In the Cox model, however, none of these factors was individually significant but rejection was more likely where≥2 preoperative risk factors were present (HR 2.11; 95% CI 1.26 to 3.47; p<0.003). CONCLUSIONS: HLA class II matching, against a background of HLA class I matching, did not reduce the risk of allograft rejection. Younger recipient age, the presence of ≥2 preoperative risk factors and cataract surgery after PK all markedly increased the risk of allograft rejection. TRIAL REGISTRATION NUMBER: ISRCTN25094892.

Quality of life of the most severely vision-impaired.

BACKGROUND: To explore the interaction between vision impairment, perceived quality of life loss and willingness to trade remaining life for vision gain. DESIGN: Community-based cross-sectional study. PARTICIPANTS: Legally blind or severely vision-impaired people selected randomly from the Association for the Blind of Western Australia register. METHODS: Individuals were examined by consultant ophthalmologists and completed the Impact of Vision Impairment profile quality of life assessment and a Time Trade-Off evaluation. Vision-related utility values were calculated. The results were analysed using univariate and multivariate regression methods. MAIN OUTCOME MEASURES: IVI Rasch Logits and TTO utility values (TTO UV). RESULTS: 156 people volunteered to contribute to the study. The median age was 80 (19-97) years, and 56% were female. Being legally blind (logMAR > 1) (95% CI 1.1 to 5.2, P = 0.003), clinically depressed (95% CI -11.2 to -1.8, P = 0.007) or more than 40 years of age (95% CI 0.9 to 8.1, P = 0.015) significantly lowered overall impact of vision impairment scores. The emotional domain of impact of vision impairment was associated with willingness to trade part of remaining life. A 5-Logit increase in impact of vision impairment emotional score resulted in a 21% (95% CI 10 to 31) decrease in the odds of being likely to trade life for sight. The Australian definition of blindness compared with World Health Organisation or USA best separates those with perceived loss and appears useful in identifying vision loss-related morbidity. CONCLUSIONS: These results suggest that emotional health and lack of depression are important determinants for quality and value of life.

Assessing the diagnostic validity of a blind register.

BACKGROUND: To validate the accuracy of clinical ophthalmic information held on the West Australian blind register. DESIGN: Community-based cross-sectional study. PARTICIPANTS: Legally blind or severely vision-impaired people were selected randomly from the Association for the Blind of Western Australia register. METHODS: Individuals were reviewed by one of two consultant ophthalmologists. MAIN OUTCOME MEASURES: The positive predictive value (ppv), sensitivity and specificity for legal blindness status and diagnostic causes of vision loss were calculated using data extracted from the Association for the Blind of Western Australia blind register. RESULTS: 273 blind or near blind people were reviewed from the register total of 4271 individuals. There were more women (57%) than men, median age 81 years. For legal blindness status the ppv was 0.88 (95% confidence interval [CI] 0.82-0.92), sensitivity 0.75 (95% CI 0.74-0.84) and specificity 0.6 (95% CI 0.46-0.73). The ppv for the diagnostic causes of blindness were: age-related macular degeneration = 0.95 (95% CI 0.91-0.97), retinitis pigmentosa ppv = 1 (95% CI 0.81-1.0), diabetic retinopathy ppv = 0.9 (95% CI 0.57-0.99), optic neuropathies ppv = 0.77 (95% CI 0.51-0.92) and glaucoma ppv = 0.87 (95% CI 0.7-0.96). Forty individuals (15%) had treatable conditions contributing to their vision loss. CONCLUSIONS: The blind register diagnoses and legal blindness status are of high accuracy. This information allows useful linkages to other databases for studies of blindness interactions. A regular updating mechanism would improve the future accuracy of this valuable regional asset. The presence of untreated cataract suggests that regular follow up and appropriate treatment may help optimize vision in blind patients.

Corneal transplant follow-up study II (CTFS II): a prospective clinical trial to determine the influence of HLA class II matching on corneal transplant rejection: baseline donor and recipient characteristics.

PURPOSE: To describe a study to determine the influence of HLA class II matching on allograft rejection of high-risk, full-thickness corneal transplants. METHODS: A prospective, longitudinal, clinical trial (ISRCTN25094892) with a primary outcome measure of time to first clinically determined rejection episode. Tissue typing used DNA-based techniques. Corneas were allocated to patients with ≤2 human leucocyte antigen (HLA) class I antigen mismatches by cohort minimisation to achieve 0, 1 or 2 HLA class II (HLA-DR) antigen mismatches. Transplants were to be followed up at 6 months and then annually on the anniversary of surgery for 5 years. Power calculations estimated a sample size of 856 transplants to detect a 0.1 difference in probability of rejection at 1 year between HLA class II matched and mismatched transplants at the 5% level of significance with 80% power. RESULTS: To allow for loss to follow-up, 1133 transplants in 980 patients were accrued to the study between 3 September 1998 and 2 June 2011. 17% of transplants had 0 HLA-DR mismatches. The most frequent indication was bullous keratopathy, accounting for 27% of transplants and 54% of the transplants were regrafts. Median waiting time for a matched graft was 3 months. Donor and recipient characteristics were distributed evenly across the study groups. CONCLUSION: Recruitment to the CFS II has closed with 1077/1133 transplants meeting all the study criteria. Follow-up has been completed and final analysis of the data has started. TRIAL REGISTRATION NUMBER: ISRCTN25094892 andUKCRNID9871, Pre-results.

Pterygia are indicators of an increased risk of developing cutaneous melanomas.

AIM: To investigate whether pterygium is an indicator of an increased risk of cutaneous melanoma (CM). METHODS: A matched-cohort study, using linked health administrative data sets to identify all hospital-treated pterygium in Western Australia (WA) between 1979 and 2014. We identified pterygium cases from hospital diagnosis and/or procedure International Classification of Diseases 9th revision (ICD-9) and 10th revision (ICD-10) codes and matched cases by age, sex and residential postcode to WA Electoral Roll controls with no known history of pterygium. Both cohorts were linked to the WA Cancer Registry and the WA Deaths Registry. RESULTS: 23 625 people had pterygium treatment (64% male) in WA hospitals. The median age for pterygium diagnosis and/or treatment was 49 years (range 14-96). There were significantly more CM cases in the pterygium cohort compared with the control cohort (1083 vs 874; p<0.001). In a logistic regression analysis, there was a 24% increase in the odds of developing a CM in the pterygium cohort, compared with controls, after controlling for other predictors (OR 1.24, 95% CI 1.1 to 1.4). The incident rate ratio (IRR) of a malignant CM diagnosis was 20% greater in people who had treatment for a pterygium compared with controls (IRR 1.2, 95% CI 1.0 to 1.4). CONCLUSION: The presence of a pterygium indicates a significantly increased risk of developing a CM. Eye care providers who see patients with developing pterygia should advise these patients of this increased risk and recommend regular skin surveillance.

Mortality and hospital morbidity of working-age blind.

AIM: Determine whether blindness in people aged 18-65 years was associated with increased rates of mortality, hospitalisation and length of stay. METHODS: A retrospective matched cohort study of legally blind people and normally sighted controls, aged 18-65 years, comparing mortality rates and hospital morbidity records. RESULTS: Together, 419 blind and 419 controls accumulated 12 258 hospital separations over the 11-year study period. The blind had an age-specific mortality rate seven times greater (12/1000 person years) than the general population (1.8/1000 person years) (p<0.001). Blindness was recorded as a comorbid condition for 76 (22%) blind individuals, on just 255 (2.3%) hospital separation records. Psychiatric, mental or behavioural conditions were the most frequently recorded diagnoses, after dialysis and endocrine conditions. After adjusting for comorbidities, the blind cohort had 1.5 times more hospital separations (p=0.007, 95% CI 1.1 to 2.0) and 2.2 times more bed days (p=0.016, 95% CI 1.4 to 4.1) compared with the control cohort. CONCLUSIONS: Recognition and acknowledgement of in-patients' blind status may assist in understanding the frequent and extended health service utilisation rates. Encouraging and promoting the uptake and access to rehabilitation support services would be measures that may reduce the health service burden of blindness, the incidence of depression and other mental health problems.