Reduction in Herpes Zoster Antiviral Use Since the Introduction of the Live-Attenuated Zoster Vaccine on Australia's National Immunisation Program: A Population-Based Study from 1994 to 2019.

INTRODUCTION: Zostavax, the live-attenuated vaccine used to prevent herpes zoster (HZ), has been available to individuals aged 70 and 71-79 years (phased catch-up) via Australia's National Immunisation Program (NIP) since 2016. There are limited data characterising the incidence of HZ at the level of the Australian population. National prescription data for antivirals used to treat HZ may be used as a proxy for HZ incidence. We aimed to examine trends in antiviral prescriptions supplied for the treatment of HZ in Australia pre- and post-2016, and to assess whether Zostavax's inclusion on the NIP correlated with a reduction in HZ antiviral prescription rates. METHODS: Using the Australian Pharmaceutical Benefits Scheme and Repatriation Pharmaceutical Benefits Scheme prescribing data, we analysed antiviral prescriptions supplied for the treatment of HZ Australia-wide between 1994 and 2019. Annual prescription rates were calculated, and trends and changes in HZ antiviral use were explored descriptively and using Poisson models. RESULTS: HZ antiviral prescription rates increased 2.6-fold (160%) between 1995 and 2015 [25.4 (95% CI 25.2, 25.6) and 65.3 (95% CI 64.9, 65.6) prescriptions per 10,000 people, respectively], and then decreased 0.45-fold (55%) between 2016 and 2018 [60.9 (95% CI 60.6, 61.2) and 27.5 (95% CI 27.3, 27.9) prescriptions per 10,000 people, respectively]. The prescription rate for the antiviral famciclovir restricted specifically for treating HZ in immunocompromised individuals increased 8.5-fold (750%) between 2006 (year first listed) and 2019 [0.3 (95% CI 0.3, 0.3) and 2.5 (95% CI 2.4, 2.6) prescriptions per 10,000 people, respectively]. CONCLUSION: The introduction of the live-attenuated HZ vaccine on Australia's formal national vaccination program was associated with a reduction in HZ antiviral prescription rates within the Australian population. The data suggest that the introduction of Shingrix, the non-live subunit zoster vaccine, may also be associated with a similar reduction in HZ antiviral prescriptions used to treat the immunocompromised, as well as the general population, given its accepted greater efficacy over Zostavax.

Prevalence of diabetic retinopathy in women with pregestational diabetes during pregnancy and the postpartum.

BACKGROUND: Diabetic retinopathy (DR) may be affected by pregnancy. The majority of prevalence data regarding DR in pregnancy predate the advent of contemporary guidelines for diabetes management during pregnancy. This study reports DR prevalence and associated risk factors in women with pregestational diabetes during pregnancy and the postpartum in Australia. METHODS: A total of 172 pregnant women with type 1 (T1DM) or type 2 diabetes diagnosed pre-pregnancy were prospectively recruited from two obstetrics hospitals in Melbourne (November 2017-March 2020). Eye examinations were scheduled in each trimester, at 3-, 6-, and 12-months postpartum. DR severity was graded from two-field fundus photographs by an independent grader utilising the Airlie House Classification. Sight-threatening DR (STDR) was defined as the presence of diabetic macular oedema or proliferative DR. RESULTS: Overall, 146 (84.9%) women had at least one eye examination during pregnancy. The mean age was 33.8 years (range 19-51), median diabetes duration was 7.0 years (IQR 3.0-17.0), 71 women (48.6%) had T1DM. DR and STDR prevalence during pregnancy per 100 eyes was 24.3 (95% CI 19.7-29.6) and 9.0 (95% CI 6.1-12.9); while prevalence in the postpartum was 22.2 (95% CI 16.5-29.3) and 10.0 (95% CI 5.4-17.9), respectively. T1DM, longer diabetes duration, higher HbA1c in early pregnancy, and pre-existing nephropathy were significant risk factors. CONCLUSIONS: The prevalence of DR in pregnant women was similar to the non-pregnant diabetic population in Australia. One in nine participants had STDR during pregnancy and the postpartum, highlighting the need to optimise DR management guidelines in pregnancy given the significant risk of vision loss.

Global Estimates of Diabetic Retinopathy Prevalence and Progression in Pregnant Women With Preexisting Diabetes: A Systematic Review and Meta-analysis.

Importance: Diabetic retinopathy (DR) may be worsened by pregnancy in pregnant women with preexisting type 1 diabetes (T1D) or type 2 diabetes (T2D). Conflicting findings from previous studies have resulted in inconsistencies in guidelines regarding DR management in pregnancy. Global estimates of DR prevalence and progression in pregnancy are therefore required to provide clearer information about the overall true burden of DR in this population. Objective: To estimate the prevalence of DR and its progression rate in pregnant women with preexisting T1D or T2D diagnosed before pregnancy. Data Sources: For this systematic review and meta-analysis, conducted from November 27, 2018, to June 29, 2021, a systematic literature search was conducted in MEDLINE/Ovid, Embase/Ovid, and Scopus databases to identify English-language articles that were published from inception through October 2020. Study Selection: Observational studies that reported on DR and its changes in pregnant women with preexisting T1D and T2D. Data Extraction and Synthesis: Two independent reviewers extracted relevant data from each included study. Data were pooled using a random-effects model with the Freeman-Tukey double arcsine transformation. This study followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Main Outcomes and Measures: Prevalence of any DR, proliferative DR (PDR), and DR progression rates. Results: A total of 18 observational studies involving 1464 pregnant women with T1D and 262 pregnant women with T2D were included in the analysis. The pooled prevalence of any DR and PDR in early pregnancy was 52.3 (95% CI, 41.9-62.6) and 6.1 (95% CI, 3.1-9.8) per 100 pregnancies, respectively. The pooled progression rate per 100 pregnancies for new DR development was 15.0 (95% CI, 9.9-20.8), worsened nonproliferative DR was 31.0 (95% CI, 23.2-39.2), progression from nonproliferative DR to PDR was 6.3 (95% CI, 3.3-10.0), and worsened PDR was 37.0 (95% CI, 21.2-54.0). DR progression rates per 100 pregnancies were similar between the T1D and T2D groups, except for the development of new DR (T1D groups: 15.8; 95% CI, 10.5-21.9; T2D groups: 9.0; 95% CI, 4.9-14.8). A global trend toward a lower DR progression rate was observed after the 1989 St Vincent Declaration. Conclusions and Relevance: Results of this systematic review and meta-analysis suggest that women with T1D and T2D had a similar risk of DR progression during pregnancy. Despite improvements in the management of diabetes and diabetes during pregnancy, DR prevalence and progression in pregnant women with diabetes remains higher than the nonpregnant population with diabetes, highlighting the need to improve DR management in pregnancy.

Epidemiology of episcleritis and scleritis in urban Australia.

IMPORTANCE: The epidemiology of episcleritis and scleritis in Australia is largely unknown. BACKGROUND: To determine the incidence, prevalence and clinical characteristics of episcleritis and scleritis in Melbourne. DESIGN: Retrospective longitudinal study. PARTICIPANTS: Patients aged ≥18 years with episcleritis or scleritis seen at the Royal Victorian Eye and Ear Hospital from November 2014 to October 2015. METHODS: Medical record review confirmed clinical diagnosis and characteristics. Incidence and prevalence were calculated using estimates of the adult population in areas of Melbourne with ≥30 ocular presentations/year to the emergency department. MAIN OUTCOME MEASURES: Diagnosis of active episcleritis or scleritis, aetiology, ocular complications and treatments. RESULTS: From a general population of 3 408 068, we confirmed 149 new and 23 pre-existing cases of active episcleritis, and 35 new and 23 pre-existing cases of active scleritis. Incidence per 100 000 person-years was 4.4 (95% confidence interval [CI] 3.7-5.1) for episcleritis and 1.0 (95% CI 0.7-1.4) for scleritis, while 12-month prevalence was 5.1 (95% CI 4.3-5.9) and 1.7 (1.3-2.2) per 100 000 persons, respectively. Systemic disease was associated with 10% of episcleritis compared with 34% of scleritis (P < .001). Ocular complications were seen in 3% (6/184) of episcleritis eyes and 44% (32/72) of scleritis eyes, with the commonest being anterior uveitis (12/72) and ocular hypertension (14/72). At presentation, scleritis patients were commonly treated with oral non-steroidal anti-inflammatory drugs (60%) and prednisolone (19%). By 12 months, 24% of scleritis patients required immunosuppressants. CONCLUSIONS AND RELEVANCE: Rates of episcleritis and scleritis in our single-centre Australian study were low. Episcleritis was usually benign, whereas scleritis had increased ocular complications and systemic disease.

The association between intravitreal ranibizumab therapy and serum cytokine concentrations in patients with diabetic macular edema.

Aim: To investigate the association between intravitreal ranibizumab therapy and serum cytokine concentrations in patients with diabetic macular edema (DME). Methods: Twenty-five patients with center-involved DME were recruited prospectively. Serum samples were collected from the patients before and 4 weeks after two ranibizumab injections. The levels of 32 cytokines at these two time points were assessed using a multiplex array assay. Results: Following two ranibizumab injections, there was a statistically significant decrease in the median [interquartile range] levels of Interleukin 1-1beta (IL-1ß) from 5.56 [3.6, 8.75] to 2.33 [1.51, 2.89], Interleukin 13 (IL-13) from 4.30 [1.84, 18.55] to 0.38 [0.38, 0.78], granulocyte-colony stimulating factor (G-CSF) from 64.65 [42.9, 108] to 37.8 [27.3, 46.37], Interferon gamma (IFN-γ) from 241 [103.33, 753.4] to 94.4626 [42.04, 118.58], Interferon gamma-induced protein 10 (IP-10) from 234.68 [144.16, 285.98] to 158.73 [94.71, 198.64], Macrophage Inflammatory Protein-1 alpha (MIP-1α) from 3.65 [2.62, 11.02] to 1.41 [0.94, 1.88], and Tumor necrosis factor- alpha (TNF-α) from 131.09 [100.68,28 240.27] to 45.19 [24.04, 68.55]. There was a statistically significant increase in the levels of Interleukin 9 (IL-9) from 0.76 [0.76, 7.03] to 19.67 [5.36 27.76], Macrophage Inflammatory Protein-1 beta (MIP-1ß) from 0.28 [0.28, 30 0.28] to 6.79 [I3.74, 14.16], Vascular endothelial growth factor (VEGF) from 2.55 [2.55, 2.55] to 25.24 [14.51, 41.73], and soluble vascular endothelial growth factor -1 (sVEGFR-1) from 333.92 [204.99, 440.43] to 500.12 [38.7, 786.91]. A Bonferroni-corrected p value of 0.00156 was considered statistically significant. Conclusions: In patients with DME, intravitreal ranibizumab therapy appears to influence the serum levels of a range of cytokines. After two injections, intravitreal ranibizumab therapy appears to be associated with a significant decrease in inflammatory mediators and a rise in VEGF and sVEGFR1.

Patterns of Vitamin D Levels and Exposures in Active and Inactive Noninfectious Uveitis Patients.

PURPOSE: To compare serum vitamin D levels and patterns of ultraviolet light and dietary exposure among patients with active and inactive noninfectious uveitis and population controls. DESIGN: Prospective case-control study. All participants (n = 151) underwent serum 25-hydroxy vitamin D measurement and completed a questionnaire on vitamin D intake and ultraviolet light exposure. Serum 25-hydroxy vitamin D levels were compared between active and inactive uveitis groups and with local population estimates. PARTICIPANTS: Adult patients with active and inactive noninfectious uveitis were recruited from 2 Victorian tertiary hospitals and 1 private ophthalmic practice. METHODS: Serum 25-hydroxy vitamin D levels were compared between patients with active and inactive uveitis and population-based estimates of serum 25-hydroxy vitamin D levels, stratified by geographic region and season. Vitamin D intakes and exposures based on questionnaire results, including vitamin D supplementation and sunlight exposures on weekdays and weekends, were compared between active and inactive uveitis groups. MAIN OUTCOME MEASURES: Serum vitamin D levels, intake of vitamin D, and exposure to sources of vitamin D. RESULTS: The median level of serum vitamin D in those with active uveitis (n = 74) was 46 nmol/l (interquartile range [IQR], 29-70 nmol/l), significantly lower than in the inactive control group (n = 77) at 64 nmol/l (IQR, 52-79 nmol/l; P < 0.001). The active uveitis group also showed lower median serum vitamin D levels than the local population median of 62 nmol/l (IQR, 46-77 nmol/l). Vitamin D supplementation also was associated significantly with uveitis inactivity (P = 0.026, Kendall's τ test). In a subanalysis of vitamin D-deficient participants, sun exposure was associated significantly with uveitis inactivity (P = 0.014 for weekday and weekend analyses). CONCLUSIONS: Participants with active uveitis showed significantly lower serum 25-hydroxy vitamin D levels than inactive uveitis patients and local population-based estimates. Vitamin D supplementation was found to be associated with decreased uveitis activity, as was sun exposure in those with vitamin D deficiency. These results suggest that vitamin D supplementation should be studied as an option for the prevention of uveitis relapse in at-risk patients.

Epidemiology of uveitis in urban Australia.

IMPORTANCE: Few prior studies have described the epidemiology of uveitis in the Australian population. BACKGROUND: To report the incidence and period prevalence of active uveitis in Melbourne and detail their subtypes and aetiologies. DESIGN: Cross-sectional study using retrospective medical record review in a tertiary hospital. PARTICIPANTS: Patients with a coded diagnosis of uveitis who attended the emergency department or specialist ocular immunology clinic at the Royal Victorian Eye and Ear Hospital between November 2014 through October 2015 (N = 1752). METHODS: Medical records were reviewed to confirm the date of diagnosis and subtype of uveitis. Incidence and prevalence rates were calculated utilizing estimates of the adult population residing in areas of greater Melbourne with more than 30 ocular-related presentations to the emergency department annually. MAIN OUTCOMES AND MEASURES: Presence and date of onset, anatomical distribution and aetiology of uveitis. RESULTS: During the study period, 734 new cases of uveitis and 502 cases of pre-existing uveitis requiring active treatment were confirmed. These figures yielded an incidence of 21.54 (CI 20.03, 23.15) per 100 000 person-years and a period prevalence of 36.27 (CI 34.30, 38.35) per 100 000 persons. The distribution of prevalent uveitis cases was anterior (75%), intermediate (6%), posterior (15%) and panuveitis (4%). An infectious aetiology accounted for 13.4% of cases, a systemic associated disease for 26.4% of cases, and no cause was identified in 60.2% of cases. CONCLUSION AND RELEVANCE: The incidence and prevalence rates of uveitis in urban Australia were lower than recent studies from the United States and Europe.

Differences in practice of ophthalmology by gender in Australia.

IMPORTANCE: The number of females practising ophthalmology is rising. It is known that practice patterns between female and male ophthalmologists differ. Understanding the differences will help to inform future workforce planning. BACKGROUND: To investigate the differences in clinical practice between female and male ophthalmologists in Australia. DESIGN: Cross-sectional study. PARTICIPANTS: Ophthalmologists participating in the Royal Australian & New Zealand College of Ophthalmologists workforce survey, and/or Medicine in Australia: Balancing Employment and Life survey, and those who made claims from Medicare Benefits Schedule Australia. METHODS: Combined analysis of de-identified 2014 data from the surveys and Medicare Benefits Schedule. MAIN OUTCOME MEASURES: Hours worked, service provision, remuneration and social circumstances. RESULTS: Female ophthalmologists provided 35% fewer services per ophthalmologist per year (2834 vs 4328) than male ophthalmologists. Female ophthalmologists received approximately half the annual income of male ophthalmologists; median self-reported net personal annual income was AUD122 500 (interquartile range [IQR] 96 000-225 000) for females compared to AUD245 000 (IQR 180 000-365 000) for males (P = .01). The median self-reported hours worked per week was 35.0 (IQR 28.0-46.0) for females and 41.8 (IQR 36.5-48.5) for males (P = 0.04). A higher proportion of females practise in medical subspecialties, while a higher proportion of males practise in surgical subspecialties. CONCLUSIONS AND RELEVANCE: Female ophthalmologists earn less compared to male ophthalmologists after accounting for lower service provision and hours worked. Difference in income may be partially accounted for by higher total number of services and procedural services provided by male ophthalmologists. Understanding differences between female and male ophthalmologists will help to inform future medical workforce planning.

Prospective randomised clinical trial of intravitreal bevacizumab versus triamcinolone in eyes with diabetic macular oedema undergoing cataract surgery: 6-month results.

AIM: To report the 6-month results of a clinical trial that compared intravitreous bevacizumab (BVB) 1.25 mg versus triamcinolone acetonide (TA) 4 mg when administered as an adjunct during cataract surgery to patients with diabetic macular oedema (DMO). METHODS: Prospective, double-masked, single-centre (Royal Victorian Eye and Ear Hospital, Melbourne) clinical trial. Patients with visually significant cataract and centre-involving DMO (either current or prior) were randomised (1: 1) to receive either intravitreous BVB 1.25 mg or TA 4 mg at the time of cataract surgery and if required at review. Main outcome measures were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline to the 6-month time point of this 12-month study. RESULTS: 61 eyes of 58 patients were enrolled. At baseline, both groups were similar in terms of BCVA and CMT (p>0.2). At 6 months, there was no significant difference in vision between the groups, with mean letter gain of +21.4 (95% CI +14.5 to +28.4) in the TA group and +17.3 (95% CI +12.1 to +22.6) in the BVB group (p=0.35). The TA group had a significant sustained anatomical improvement at 6 months, with a reduction in CMT (-51.4 µm; 95% CI -98.2 to -4.7) compared with thickening in the BVB group (+15.6 µm; 95% CI -26.4 to +57.7, p=0.04). CONCLUSIONS: When given as an adjunct to cataract surgery, both TA and BVB improved visual outcomes at 6 months postoperatively. However, only TA resulted in sustained improvement in CMT, with the majority not requiring any further treatment postoperatively.

Sarcoidosis-related Uveitis: Clinical Presentation, Disease Course, and Rates of Systemic Disease Progression After Uveitis Diagnosis.

OBJECTIVE: To document the clinical presentation, treatment, and visual outcome of sarcoid uveitis and to determine the timing and potential risk factors of sarcoidosis progression to symptomatic systemic disease from the time of sarcoid uveitis diagnosis. DESIGN: Retrospective, interventional case series. METHODS: Subjects: Patients with dual diagnoses of uveitis and presumed/biopsy-proven sarcoidosis. PROCEDURE: Retrospective review of 143 patient records from the Royal Victorian Eye and Ear Hospital and Eye Surgery Associates in Melbourne, Australia, between October 1990 and April 2014 coded with the dual diagnoses of uveitis and sarcoidosis. Only patients with uveitis and presumed or biopsy-proven sarcoidosis (N = 113) were included. MAIN OUTCOME MEASURES: Ascertainment of rate and time (months) to the development of symptomatic systemic sarcoidosis from uveitis onset; comparison of the patient demographics, characteristics of uveitis, treatment, and visual outcome between those who developed systemic sarcoidosis and those who remained systemically asymptomatic. RESULTS: Uveitis was the initial presenting complaint of sarcoidosis in 78.8% (n = 89). Twenty-three patients had concurrent undiagnosed systemic disease at presentation and 29 subsequently developed symptomatic sarcoidosis in an organ uninvolved at uveitis onset. The median time to the development of symptomatic systemic sarcoidosis was 12 months. No statistically significant association was ascertained between any particular uveitis characteristic and extraocular sarcoidosis progression. CONCLUSION: Uveitis was the initial presentation of sarcoidosis in the vast majority of our subjects. Concurrent undiagnosed systemic sarcoidosis was common at the time of uveitis onset. A high index of suspicion for subsequent systemic progression should also be maintained, especially within the first 5 years of the uveitis diagnosis.

The Influence of Intravitreal Ranibizumab on Inflammation-associated Cytokine Concentrations in Eyes With Diabetic Macular Edema.

Purpose: To evaluate the effect of intravitreal ranibizumab injections on aqueous concentrations of angiogenic or inflammatory cytokines in patients with diabetic macular edema (DME). Methods: Thirty eyes of 25 patients with center-involved DME were recruited to the study. All had a central macular thickness (CMT) of >300 µm and best-corrected visual acuity (BCVA) between 28 and 70 logMAR letters (Snellen equivalent 20/320-20/40). At baseline, all eyes had 0.1 mL of aqueous collected before ranibizumab treatment. At week 4, a second ranibizumab injection was administered and at week 8, aqueous sampling was repeated before a third ranibizumab injection. From week 12, all eyes were followed at 4-weekly intervals and the need for ranibizumab treatment was determined by BCVA and CMT measurements. Levels of 32 cytokines were assessed at baseline and at week 8 using a multiplex array assay. Results: Following two consecutive ranibizumab injections, there was a statistically significant reduction in VEGF (P < 0.00001), as well as IL-1ß (P = 0.00006), IL-7 (P = 0.00002), IL-8 (P = 0.00023), IL-10 (P < 0.00001), IL-12 (P < 0.00001), IL-17 (P = 0.00024), MCP-1 (P = 0.00023), and TNF-α (P < 0.00001). There was also an upregulation of soluble VEGF receptor-2 (P = 0.00004). A P < 0.0015 was considered significant in this study. Conclusions: Ranibizumab treatment influences various inflammatory cytokine concentrations in addition to reducing aqueous VEGF concentrations in patients with DME. This may contribute to its therapeutic effect in patients with DME.

Association Between Diabetes-Related Eye Complications and Symptoms of Anxiety and Depression.

IMPORTANCE: This study is needed to clarify inconsistent findings regarding the association between diabetes-related eye complications and psychological well-being. OBJECTIVE: To examine the association between severity of diabetic retinopathy (DR) and diabetic macular edema (DME) with symptoms of depression and anxiety in adults with diabetes. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional study was conducted in a tertiary eye hospital in Melbourne, Australia. The study comprised 519 participants with diabetes. The median duration of diabetes was 13.0 (interquartile range, 14.0) years. The study was conducted from March 1, 2009, to December 24, 2010. EXPOSURES: Patients underwent a comprehensive eye examination in which dilated fundus photographs (disc and macula centered) were obtained and graded for the presence and severity of DR and DME. Presenting distance uniocular and binocular visual acuity were assessed using a 3-m logMAR chart. MAIN OUTCOMES AND MEASURES: Symptoms of depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS), which comprises 7 questions specific to anxiety and 7 specific to depression with scores ranging from 0 to 21; scores higher than 8 signify possible anxiety or depression. The ordinal raw scores of the HADS questionnaire were transformed to estimates of interval measure using Rasch analysis and evaluated as continuous variables. Participants also completed standardized interview-administered questionnaires. Blood samples were assessed for hemoglobin A1c, fasting blood glucose, and serum lipids. Multiple linear regression models were used to determine the associations between the severity of DR and DME with symptoms of anxiety and depression and commonality analysis was used to quantify the unique variance explained. RESULTS: Of the 519 participants in the study, 170 individuals (32.8%) were female; mean (SD) age was 64.9 (11.6) years. Raw scores indicated that 80 individuals (15.4%) screened positive for depressive symptoms and 118 persons (22.7%) screened positive for symptoms of anxiety. In multivariate analysis using Rasch scores, severe nonproliferative DR (NPDR)/PDR was independently associated with greater depressive symptoms (regression coefficient [ß] = 0.69; 95% CI, 0.03-1.34) after controlling for sociodemographic factors and clinical characteristics, including visual acuity. A history of depression or anxiety accounted for 60.6% (95% CI, 23.9%-83.2%) of the unique variance in depressive symptoms, and severe NPDR or PDR contributed to 19.1% (95% CI, 1.7%-44.4%) of the total explained variance of depressive symptoms. Diabetic macular edema was not associated with depressive symptoms. No association between DR and symptoms of anxiety was identified. CONCLUSIONS AND RELEVANCE: Severe NPDR or PDR, but not DME, was independently associated with depressive symptoms. The severity of DR could be an indicator to prompt monitoring of depression in at-risk individuals with diabetes. Further work is required to replicate these findings and determine the clinical significance of the association.

Hypertensive retinopathy: comparing the Keith-Wagener-Barker to a simplified classification.

PURPOSE: This study assessed the interobserver and intraobserver grading reliability of the Keith-Wagener-Barker (KWB) system to the proposed Mitchell-Wong 'simplified' three-grade classification for hypertensive retinopathy. METHODS: Digital retinal images of normal and hypertensive human fundii (n = 50 per group) were randomly graded by an optometrist and an ophthalmologist using the two systems. Interobserver agreement was compared to a 'gold standard' research grader. Intraobserver agreement was assessed through a repeat grading after 6 months. Cohen's kappa coefficients were used to assess the degree of agreement. RESULTS: Both clinicians demonstrated a good level of agreement with the KWB and simplified classification compared with a 'gold standard' grader; there was no significant difference in the level of agreement for either of the two classification methods for either observer. The simplified classification was found to be equally as efficacious as the KWB system with respect to interobserver and intraobserver agreement for both practitioners. CONCLUSION: These findings indicate that the simplified classification of hypertensive retinopathy is both reliable and repeatable. The advantage of the simplified method over the KWB system in correlating retinal microvascular signs to incident cardiovascular risk supports its adoption in clinical practice.

Global prevalence and major risk factors of diabetic retinopathy.

OBJECTIVE: To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS: A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20-79 years. RESULTS: A total of 35 studies (1980-2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5-34.8) for any DR, 6.96% (6.87-7.04) for proliferative DR, 6.81% (6.74-6.89) for diabetic macular edema, and 10.2% (10.1-10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A(1c), and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS: There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.

Natural history of central retinal vein occlusion: an evidence-based systematic review.

OBJECTIVE: To describe the natural history of central retinal vein occlusion (CRVO) based on the best available evidence from the literature. CLINICAL RELEVANCE: Central retinal vein occlusion is a common sight-threatening retinal vascular disease. Despite the introduction of new interventions, the natural history of CRVO is unclear. METHODS: Systemic review of all English language articles retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008. This was supplemented by hand-searching references of review articles published within the last 5 years. Two investigators independently identified all relevant observational studies evaluating the natural history of RVO and all clinical trials evaluating interventions for CRVO; an untreated control arm was included. RESULTS: Of 5966 citations retrieved, 53 studies were reviewed, providing 3271 eyes with CRVO for analysis of its natural history. Visual acuity (VA) was generally poor at baseline (<20/40) and decreased further over time. Although 6 studies reported an improvement in VA, none of these improvements resulted in VA better than 20/40. Up to 34% of eyes with nonischemic CRVO converted to ischemic CRVO over a 3-year period. In ischemic CRVO cases, neovascular glaucoma developed in at least 23% of eyes within 15 months. In nonischemic CRVO cases, macular edema resolved in approximately 30% of eyes over time, and subsequent neovascular glaucoma was rare. CONCLUSIONS: Untreated eyes with CRVO generally had poor VA, which declined further over time. One quarter of eyes with nonischemic CRVO converted to ischemic CRVO.

Natural history of branch retinal vein occlusion: an evidence-based systematic review.

OBJECTIVE: To describe the natural history of branch retinal vein occlusion (BRVO) based on the best available evidence from the literature. CLINICAL RELEVANCE: Branch retinal vein occlusion is the second most frequent major retinal vascular disease. Although several new treatments for BRVO are currently being introduced, data on its natural history are sparse. METHODS: English language articles were retrieved using a keyword search of MEDLINE, EMBASE, Current Contents, and the Cochrane Library to November 13, 2008, supplemented by manually searching the references of review articles published within the last 5 years. All relevant observational studies evaluating the natural history of BRVO and all clinical trials evaluating BRVO interventions with an untreated control arm were independently identified by 2 investigators. RESULTS: Of a total of 5965 citations retrieved, 24 eligible studies were identified and reviewed, providing 1608 eyes with BRVO with data on natural history. Visual acuity (VA) was moderately poor at baseline (<20/40). Although VA generally improved, with mean improvement ranging from 1 letter at 6 weeks to 28 letters up to 24 months, few studies reported improvement beyond 20/40. Over a 1-year period, 5% to 15% of eyes developed macular edema (ME), but of those with ME at baseline, 18% to 41% resolved. At baseline, 5% to 6% of eyes had bilateral BRVO, with 10% developing fellow eye involvement over time. There were few high-quality studies on other outcomes, including development of new vessels. CONCLUSIONS: Visual acuity generally improved in eyes with BRVO without intervention, although clinically significant improvement beyond 20/40 was uncommon.

Quantitative assessment of early diabetic retinopathy using fractal analysis.

OBJECTIVE: Fractal analysis can quantify the geometric complexity of the retinal vascular branching pattern and may therefore offer a new method to quantify early diabetic microvascular damage. In this study, we examined the relationship between retinal fractal dimension and retinopathy in young individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional study of 729 patients with type 1 diabetes (aged 12-20 years) who had seven-field stereoscopic retinal photographs taken of both eyes. From these photographs, retinopathy was graded according to the modified Airlie House classification, and fractal dimension was quantified using a computer-based program following a standardized protocol. RESULTS: In this study, 137 patients (18.8%) had diabetic retinopathy signs; of these, 105 had mild retinopathy. Median (interquartile range) retinal fractal dimension was 1.46214 (1.45023-1.47217). After adjustment for age, sex, diabetes duration, A1C, blood pressure, and total cholesterol, increasing retinal vascular fractal dimension was significantly associated with increasing odds of retinopathy (odds ratio 3.92 [95% CI 2.02-7.61] for fourth versus first quartile of fractal dimension). In multivariate analysis, each 0.01 increase in retinal vascular fractal dimension was associated with a nearly 40% increased odds of retinopathy (1.37 [1.21-1.56]). This association remained after additional adjustment for retinal vascular caliber. CONCLUSIONS: Greater retinal fractal dimension, representing increased geometric complexity of the retinal vasculature, is independently associated with early diabetic retinopathy signs in type 1 diabetes. Fractal analysis of fundus photographs may allow quantitative measurement of early diabetic microvascular damage.

Readability of prescription labels and medication recall in a population of tertiary referral glaucoma patients.

PURPOSE: To evaluate readability of eye drop labels and accurate recall of prescription instructions in a glaucoma population. METHODS: A hospital-based, cross-sectional study. A trained, interviewer examined patient ability to read standard and larger font medication labels. A questionnaire was administered to ascertain accurate recall of prescribed eye drops. Clinical information was obtained through independent chart review. Glaucoma severity was classified according to a glaucoma staging system. The setting for the study was the glaucoma outpatient clinic, Royal Victorian Eye and Ear Hospital (Melbourne, Australia), a major tertiary referral centre. A total of 200 glaucoma patients (96.2% response), aged 45-90 years, on eye drops took part in the study. Non-English-speaking patients were excluded. The main outcome measure was the ability to read prescribed medication labels and accurately recall treatment regime was compared with glaucoma severity and the number of eye drops. RESULTS: Of the glaucoma patients, 12% were unable to read standard pharmacy labels. Only 5.5% were unable to read the larger font labels. Of the patients, 32% were not able to accurately recall the type of drops or prescribed frequency of instillation. An inability to read standard labels was associated with a threefold reduction in the likelihood of accurate medication recall (95% confidence intervals, 1.40-7.66, P < 0.05). Patients with three or more types of eye drops were five times less likely to recall their medications (95% confidence interval, 0.07-0.57, P < 0.05). CONCLUSIONS: Inability to read or recall prescribed eye drops was associated with glaucoma severity and the number of prescribed eye drops. These factors may impact significantly on patients' adherence to glaucoma medications.

How do the Australian guidelines for lipid-lowering drugs perform in practice? Cardiovascular disease risk in the AusDiab Study, 1999-2000.

OBJECTIVE: To determine how well the current Pharmaceutical Benefits Scheme (PBS) eligibility criteria for subsidy of lipid-lowering drugs compare with current national guidelines for determining the population at high risk of developing cardiovascular disease (CVD). DESIGN AND PARTICIPANTS: Analyses of the population-based, cross-sectional Australian Diabetes, Obesity and Lifestyle (AusDiab) study, conducted in 1999-2000. The 1991 Framingham risk prediction equation was used to compute 5-year risk of developing first-time CVD in 8286 participants aged 30-74 years with neither CVD nor diabetes. Based on the National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand guidelines, people with either 5-year CVD risk > or = 15% or with 5-year CVD risk of 10%-< 15% and the metabolic syndrome were defined as having estimated high absolute CVD risk. MAIN OUTCOME MEASURES: 5-year CVD risk; estimated population with high CVD risk. RESULTS: Among participants without prevalent CVD or diabetes, 7.9% of men and 1.5% of women had a 5-year CVD risk > or = 15%. Of the estimated residential Australian population in 2000 aged 30-74 years without CVD or diabetes, 717 000 people were considered to be at high absolute CVD risk. Among the high-risk AusDiab participants without CVD or diabetes, only 16.9% of men and 15.4% of women were being treated with lipid-lowering drugs. Of the 9.6% of participants free of CVD and diabetes who were untreated but eligible for subsidy under PBS criteria, only 27.4% had an estimated high absolute CVD risk. CONCLUSION: Strategies for CVD prevention using lipid-lowering medications can be improved by adoption of the absolute-risk approach.

Retinal vascular caliber changes after intravitreal triamcinolone treatment for diabetic macular edema.

PURPOSE: To describe the changes in retinal vascular caliber in response to a single injection of intravitreal triamcinolone (IVTA) in patients with refractory diabetic macular edema. METHODS: Prospective data from a randomized clinical trial were used. The effects of IVTA versus sham injections in patients with refractory diabetic macular edema were evaluated in a randomized clinical trial involving 69 eyes of 43 patients. Of these, 28 eyes (15 IVTA and 13 sham) of 21 patients had gradable retinal photographs at the baseline and 3-month follow-up visit for analysis in the present study. Retinal vascular caliber was measured from digital fundus photographs and summarized as central retinal artery (CRAE) and vein (CRVE) equivalents in all eyes at baseline and at the 3-month follow-up visit. RESULTS: Over the 3 months of the study, there was a significant reduction compared to baseline in retinal arteriolar (147.8 microm vs. 140.0 microm, P = 0.047) and venular (219.5 microm vs. 198 microm, P = 0.039) caliber in eyes treated with IVTA. There was no change in retinal arteriolar (139.9 microm vs. 139.2 microm, P = 0.878) or venular (220.3 microm vs. 217.6 microm, P = 0.534) caliber in those treated with sham injections. CONCLUSIONS: IVTA has a significant narrowing effect on both retinal arteriolar and venular diameter in eyes with diabetic macular edema (ClinicalTrials.gov number, NCT00148330).