C Alex Harper

Longitudinal Association of Glucose Metabolism With Retinopathy: Results from the Australian Diabetes Obesity and Lifestyle (AusDiab) study

OBJECTIVE—We determined the longitudinal association of glucose metabolism with retinopathy in a sample of the Australian population. RESEARCH DESIGN AND METHODS—The Australian Diabetes Obesity and Lifestyle (AusDiab) study is a national, longitudinal study of adults aged ≥25 years from 42 randomly selected areas of Australia. Retinopathy was assessed at baseline in 1999–2000 and 5 years later in 2004–2005 in participants identified as having diabetes (based on self-report and oral glucose tolerance test) and impaired glucose metabolism and in a random sample with normal glucose tolerance. Complete retinal data were available for 1,192 participants. Photographs were graded at two time points according to a simplified version of the Wisconsin grading system. RESULTS—The 5-year incidences of retinopathy were 13.9 and 3.0% among those with known and newly diagnosed diabetes at baseline, respectively. Of those who developed incident newly diagnosed diabetes at follow-up, 11.9% had retinopathy at baseline compared with 5.6% of those who did not progress to incident newly diagnosed diabetes (P = 0.037). After adjustment for factors identified as risk factors for diabetes, individuals with retinopathy signs at baseline were twice as likely to develop incident newly diagnosed diabetes compared with those who did not have retinopathy signs at baseline. CONCLUSIONS—The 5-year incidence of retinopathy was 13.9% among individuals with known diabetes. Nondiabetic individuals with retinopathy signs at baseline had a twofold higher risk of developing incident newly diagnosed diabetes 5 years later. This result provides further evidence that mild retinopathy signs may be a preclinical marker of underlying microvascular disease and future diabetes risk.

Aging Changes in Bruch's Membrane

Using histochemical staining techniques and electron microscopy, the authors have examined the histochemical properties and ultrastructure of Bruchs membrane in 30 human eyes with an age range of 1 to 95 years. The results analyzed in three age groups (0-30 years, 31-60 years, and older than 60 years) show that there is a progressive accumulation of lipids in Bruchs membrane with relation to age. Differences were found in the specific types of lipids in individual eyes. Five eyes stained for neutral lipids alone, four stained predominantly for phospholipids, and nine stained intensely for both neutral lipids and phospholipids. The deposits were associated with the progressive destruction of the native architecture of Bruchs membrane but no correlation was identified between specific inclusions in Bruchs membrane with a particular lipid. These results are significant to age-related macular disease (ARMD), and the lipid rich barrier in Bruchs membrane is implicated as a cause of photoreceptor dysfunction and pigment epithelial detachment.

Five‐year incidence of diabetic retinopathy in the Melbourne Visual Impairment Project

Background: The purpose of the present paper was to describe the 5‐year incidence and progression of diabetic retinopathy in the Melbourne Visual Impairment Project (VIP) cohort.

Is peripheral neuropathy associated with retinopathy and albuminuria in individuals with impaired glucose metabolism? The 1999-2000 AusDiab.

Individuals with impaired glucoses tolerance (IGT) or impaired fasting glucose (IFG) are at substantially increased risk of developing diabetes and cardiovascular disease (1). The extent to which individuals with IGT/IFG are also at risk of microvascular complications, such as neuropathy, retinopathy, and nephropathy, has not been as well defined. Some (2,3), but not all (4 –7), studies have shown that microvascular complications are more common in individuals with IGT/IFG than those with normal glucose metabolism. Peripheral neuropathy, a common microvascular complication of diabetes (8), is often associated with concomitant retinopathy (9) and albuminuria (9,10). Whether peripheral neuropathy is also associated with retinopathy and albuminuria in people with IGT/IFG is unclear and is examined in the current study.

Primary treatment of choroidal amelanotic melanoma with photodynamic therapy

The management of choroidal melanoma involves a delicate balance between preserving vision and preventing metastasis. Plaque brachytherapy has become standard management of most small lesions; however, this can result in radiation retinopathy and optic neuropathy. Transpupillary thermotherapy avoids these side‐effects; however, it can also result in visual loss and its effectiveness is limited in amelanotic lesions. Photodynamic therapy with verteporfin has shown promise in animal studies of choroidal melanoma, and has recently been used in the management of lesions that have failed to respond to conventional therapy. The authors report a case of primary treatment of a small choroidal amelanotic melanoma with photodynamic therapy using verteporfin.

Examination compliance and screening for diabetic retinopathy: a 2‐year follow‐up study

Early detection and timely treatment of diabetic retinopathy can preserve vision, yet many people with diabetes do not have their eyes examined regularly. The purpose of this study was to examine eye care practices of people with diabetes who had not previously accessed eye care services on a regular basis. Screening with non‐mydriatic retinal photography for diabetic retinopathy was initiated in 1996, and targeted people with diabetes who did not access eye care services on a regular basis. Each test area was revisited 2 years after the initial screening. Patients that did not attend the biennial screening were followed up by mail survey. Although none of the participants in this study had been previously accessing eye care services on a regular basis, 87% did so after attending the screening. These results indicate that mobile screening with non‐mydriatic photography, as an adjunct to current eye care services, has the potential to increase examination compliance for diabetic retinopathy and to achieve sustained behaviour change.

Ocular–central nervous system lymphoma mimicking posterior scleritis with exudative retinal detachment

OBJECTIVE We describe an unusual ocular presentation of ocular-central nervous system lymphoma in a young patient. DESIGN Interventional case report and literature review. METHODS A previously well 24-year-old white woman presented with left eye pain and reduced vision. Episcleral injection, globe tenderness, an afferent pupil defect, and exudative retinal detachment were present. Computed tomographic scan of the head and orbits demonstrated scleral thickening, retinal detachment, and no other abnormality. A provisional diagnosis of posterior scleritis with exudative retinal detachment was made. Investigation for underlying connective tissue diseases was negative. There was an initial prompt response to corticosteroid therapy. The patients symptoms and signs then recurred, and a left third cranial nerve palsy developed. Systemic investigations including lumbar puncture ultimately led to the diagnosis of primary T-cell central nervous system (CNS) lymphoma. Serologic tests for human immunodeficiency virus were negative. MAIN OUTCOME MEASURES AND RESULTS The patient underwent orbital and cranial irradiation and intrathecal and systemic chemotherapy. Despite an initial response to treatment, she returned with a recurrence of the lymphoma in the anterior segment of the left eye. Her systemic disease progressed rapidly, and she died shortly thereafter. CONCLUSIONS This patients young age and initial presentation mimicking posterior scleritis with unilateral exudative retinal detachment, without evidence of vitreous involvement, are highly unusual for ocular involvement in primary CNS lymphoma. A review of the literature highlights the atypical nature of this presentation.

Increased serum kallistatin levels in type 1 diabetes patients with vascular complications

BackgroundKallistatin, a serpin widely produced throughout the body, has vasodilatory, anti-angiogenic, anti-oxidant, and anti-inflammatory effects. Effects of diabetes and its vascular complications on serum kallistatin levels are unknown.MethodsSerum kallistatin was quantified by ELISA in a cross-sectional study of 116 Type 1 diabetic patients (including 50 with and 66 without complications) and 29 non-diabetic controls, and related to clinical status and measures of oxidative stress and inflammation.ResultsKallistatin levels (mean(SD)) were increased in diabetic vs. control subjects (12.6(4.2) vs. 10.3(2.8) μg/ml, p = 0.007), and differed between diabetic patients with complications (13.4(4.9) μg/ml), complication-free patients (12.1(3.7) μg/ml), and controls; ANOVA, p = 0.007. Levels were higher in diabetic patients with complications vs. controls, p = 0.01, but did not differ between complication-free diabetic patients and controls, p > 0.05. On univariate analyses, in diabetes, kallistatin correlated with renal dysfunction (cystatin C, r = 0.28, p = 0.004; urinary albumin/creatinine, r = 0.34, p = 0.001; serum creatinine, r = 0.23, p = 0.01; serum urea, r = 0.33, p = 0.001; GFR, r = -0.25, p = 0.009), total cholesterol (r = 0.28, p = 0.004); LDL-cholesterol (r = 0.21, p = 0.03); gamma-glutamyltransferase (GGT) (r = 0.27, p = 0.04), and small artery elasticity, r = -0.23, p = 0.02, but not with HbA1c, other lipids, oxidative stress or inflammation. In diabetes, geometric mean (95%CI) kallistatin levels adjusted for covariates, including renal dysfunction, were higher in those with vs. without hypertension (13.6 (12.3-14.9) vs. 11.8 (10.5-13.0) μg/ml, p = 0.03). Statistically independent determinants of kallistatin levels in diabetes were age, serum urea, total cholesterol, SAE and GGT, adjusted r2 = 0.24, p < 0.00001.ConclusionsSerum kallistatin levels are increased in Type 1 diabetic patients with microvascular complications and with hypertension, and correlate with renal and vascular dysfunction.

Diabetic retinopathy management guidelines

Diabetic retinopathy (DR) is an important cause of avoidable blindness worldwide. Seventy percent of diabetes occur in low and lower-middle income countries. Clinical practice guidelines for the management of DR have been implemented throughout the world, but mainly in developed nations. However, there is considerable variation between existing guidelines in the recommended frequency of referral, methods for examination and personnel involved in screening and review. This review compares the differences between current available guidelines in the context of the current medical evidence and also addresses the implications for management of DR in countries with limited resources.

Cardiovascular Adverse Effects of Phenylephrine Eyedrops A Systematic Review and Meta-analysis

IMPORTANCE Topical phenylephrine hydrochloride is routinely administered with few safety precautions, but evidence regarding its systemic safety to date is controversial. As even short-term variations in 24-hour blood pressure (BP) and heart rate (HR) can adversely affect cardiovascular health, better evidence on phenylephrines effects on HR and BP is required. OBJECTIVE To perform a meta-analysis of available evidence regarding cardiovascular adverse effects of topical phenylephrine. DATA SOURCES PubMed, MEDLINE, and the Cochrane Database of Systematic Reviews and Clinical Trials were searched for relevant literature from January 1, 1970, to January 1, 2014, using a combination of the following search terms: topical, ocular, ophthalmic, phenylephrine, tropicamide, cardiovascular effect, side effect, blood pressure, heart rate, mydriatic, and eye drops. A total of 70 articles related to the topic were identified and all full texts were retrieved. STUDY SELECTION Randomized clinical trials reporting change in BP and HR for adults were included in this review. All studies reporting results for neonates or infants, not reporting standard deviations, or not specifying the time of measurement or the concentration of phenylephrine used were excluded. DATA EXTRACTION AND SYNTHESIS Data from randomized clinical trials that reported BP and/or HR as well as the time following administration of topical phenylephrine at which measurements were obtained by concentration of phenylephrine as a mean change and its standard deviation were extracted. Data were synthesized by concentration of phenylephrine and time of measurement following topical application using random-effects models with inverse variance weighting to account for heterogeneity across studies. MAIN OUTCOMES AND MEASURES Difference in BP and HR after topical administration of phenylephrine. RESULTS Eight RCTs with a total of 916 participants were included. Data were available for phenylephrine, 2.5%, at 20 to 30 minutes and 60 minutes or longer after administration, and neither BP nor HR changed at either time. Following application of phenylephrine, 10%, BP increased at 5 and 10 minutes (mean difference for both, +15 mm Hg; 95% CI, 11.94-18.54; P < .001) but decreased at 20 to 30 minutes and 60 minutes or longer with no changes detected against baseline. A mean increase in HR by 4.48 beats/min (95% CI, 1.09-7.88; P = .01) was present at 20 to 30 minutes following application of phenylephrine, 10%, and HR decreased by 60 minutes or longer with no changes detected compared with baseline. CONCLUSIONS AND RELEVANCE Phenylephrine, 2.5%, leads to no clinically relevant change in BP or HR, and the changes in BP and HR seen with phenylephrine, 10%, are short lived. Thus, phenylephrine, 2.5%, is safe to use in clinical routine.