The retinopathy of prematurity: a study of incidence and the identification of those babies at risk: myopia associated with prematurity

The ocular problems associated with premature birth have been with us ever since it was discovered that the application of high levels of inspired oxygen provided a reduction in mortality. The consequence of this reduction in mortality has been a rise in morbidity; these mortality and morbidity rates have oscillated during the attempt to find a reasonable balance. The use of contemporary technology during the attempt both to understand the premature baby's delicate physiology and to maintain life to younger and lighter babies has not yet produced stability. The incidence of typical retinal maldevelopment, retinopathy of prematurity (RCP), was analysed by serial weekly ophthalmoscopy examinations in a regional special care baby unit, 579 examinations being made on 138 babies. The best instrument for this examination was found to be a compact indirect ophthalmoscope incorporating an inverting eyepiece - the Reichert Jung monocular indirect ophthalmoscope. The optimum time for ocular examination to discover potential ocular morbidity was at 33 weeks post-conceptual age (PCA) with continued examinations to the age of 37 weeks PCA. The babies that were found to be at risk of a significant grade of RCP were found to be of a birth weight of less than 1251 grams or had an estimated gestational age at birth of 30 weeks or less. A refractive state of myopia was found to be the norm. The myopia reduced as life progressed to attain emmetropia around the age of 50 weeks PCA or 22 weeks survival. The reduction of the myopic state was found to be dependent on birth weight and gestational age at birth, the youngest and therefore the lightest being more predictable in attaining emmetropia. Refractive variations were found to be coincident with the timings of certain medical treatment regimes and a hypothesis is postulated as to the mechanism of this association.

Higher prevalence of retinopathy in diabetic patients of South Asian ethnicity compared with white Europeans in the community:a cross-sectional study

OBJECTIVE—The purpose of this study was to compare prevalence and risk factors for diabetic retinopathy among U.K. residents of South Asian or white European ethnicity. RESEARCH DESIGN AND METHODS—This was a community-based cross-sectional study involving 10 general practices; 1,035 patients with type 2 diabetes were studied: 421 of South Asian and 614 of white European ethnicity. Diabetic retinopathy, sight-threatening retinopathy, maculopathy, and previous laser photocoagulation therapy were assessed after grading of retinal photographs. Data were collected on risk factors including age, duration, and treatment of diabetes, blood pressures, serum total cholesterol, and A1C. RESULTS—Patients of South Asian ethnicity had significantly higher systolic (144 vs. 137 mmHg, P < 0.0001) and diastolic (84 vs. 74 mmHg, P < 0.0001) blood pressure, A1C (7.9 vs. 7.5%, P < 0.0001), and total cholesterol (4.5 vs. 4.2 mmol/l, P < 0.0001). Diabetic retinopathy was detected in 414 (40%) patients (189 South Asian [45%] versus 225 white European [37%]; P = 0.0078). Sight-threatening retinopathy was detected in 142 (14%) patients (68 South Asian [16%] versus 74 white European [12%]; P = 0.0597). After adjustment for confounders, there were significantly elevated risks of any retinopathy and maculopathy for South Asian versus white European patients. CONCLUSIONS—Patients of South Asian ethnicity had a significantly higher prevalence of diabetic retinopathy and maculopathy, with significantly elevated systolic and diastolic blood pressure, A1C, and total cholesterol; lower attained age; and younger age at diagnosis. Earlier onset of disease and higher levels of modifiable risk factors make early detection of diabetes, annual referral for retinal screening, and intensive risk factor control key elements in addressing this health inequality.

Evaluating digital diabetic retinopathy screening in people aged 90 years and over

Introduction: The English National Screening Programme determines that all people with diabetes aged 12 and over should be screened annually for diabetic retinopathy (DR) until they die. Purpose: This study aimed to evaluate digital DR screening in patients aged 90 and over to establish whether it is appropriate to cease screening at age 90. Methods: A retrospective analysis of 200 randomly selected patients with diabetes aged 90 and over within the Birmingham and Black Country Screening Programme. Results: 179 (90%) patients attended screening at least once after turning 90 years of age. To date, the mean number of screens per person 90+ was two (range 1–6) and the mean age of the first of these screens was 91 years (range 90–98 years). 133 (74%) were put on annual recall after their first screen in their 90’s, of which 58% had no visible DR bilaterally. 38 (21%) were referred to ophthalmology - 35 (92%) for non-DR reasons and three for maculopathy. Of the 133 patients put on annual recall, 75 (56%) were screened at least once more. Seven improved, 36 remained stable, three became unsuitable and 29 deteriorated. Of the latter, 18 patients were referred to ophthalmology; one of these for DR. Conclusion: Patients with diabetes aged 90 and over are at low risk of sight threatening DR and annual screening in this age group may be unnecessary. However, annual screening does provide opportunistic identification.

Is twelve years old an acceptable age at which to begin Diabetic Retinopathy Screening?

Introduction: The English National Screening Programme for diabetic retinopathy (ENSPDR) states that “all people with diabetes aged 12 years and over should be offered screening” Purpose: The audit aims to assess whether the current guideline is suitable and whether diabetes duration should be taken into account when deciding at what age to start screening patients. Method: Retrospective analysis of 143 randomly selected patients aged twelve years or younger who have attended diabetic retinopathy (DR) screening in the Birmingham and Black Country Screening Programme. Results: 98% had Type 1 diabetes and mean visual acuity (VA) was 6/5 (6/4-6/36). 73 were under 12 with 7 the youngest age and 70 were aged 12. Both groups had mean diabetes duration of 5 years (1month-11years). For those under 12, 7/73 (9.6%) had background DR, of these mean diabetes duration was 7 years (6-8) and the youngest aged 8. In those aged 12, 5/70 (7.1%) had background DR; of these mean diabetes duration was 8 years (6-11). In total 12 (8.4%) patients aged 12 years or under developed DR. No patients had retinopathy worse than background changes. One patient was referred to ophthalmology for VAs of 6/12, 6/18 and was diagnosed with optic atrophy so returned to annual screening. Conclusion: The results suggest that the current guideline on when to begin screening should be readdressed as more patients under twelve developed DR than those aged 12. Diabetes duration may help when deciding what age to start screening adolescent patients as DR was not seen in those with disease duration.

What is the prevalence of diabetic macular oedema involving the centre of the macula in patients undergoing digital diabetic retinopathy screening

Free Paper Sessions Design. Retrospective analysis. Purpose. To assess the prevalence of center-involving diabetic macular oedema (CIDMO) and risk factors. Methods. Retrospective review of patients who were screen positive for maculopathy (M1) during 2010 in East and North Birmingham. The CIDMO was diagnosed by qualitative identification of definite foveal oedema on optical coherence tomography (OCT). Results. Out of a total of 15,234 patients screened, 1194 (7.8%) were screen positive for M1 (64% bilateral). A total of 137 (11.5% of M1s) were diagnosed with macular oedema after clinical assessment. The OCT results were available for 123/137; 69 (56.1%) of these had CI-DMO (30 bilateral) which is 0.5% of total screens and 5.8% of those screen positive for M1. In those with CIDMO 60.9% were male and 63.8% Caucasian; 90% had type 2 diabetes and mean diabetes duration was 20 years (SD 9.7, range 2-48). Mean HbA1c was 8.34%±1.69, with 25% having an HbA1c =9%. Furthermore, 62% were on insulin, 67% were on antihypertensive therapy, and 64% were on a cholesterol-lowering drug. A total of 37.7% had an eGFR between 30% and 60% and 5.8% had eGFR <30. The only significant difference between the CIDMO and non-CIDMO group was mean age (67.83±12.26 vs 59.69±15.82; p=0.002). A total of 65.2% of those with CIDMO also had proliferative or preproliferative retinopathy in the worst eye and 68.1% had subsequently been treated with macular laser at the time of data review. Conclusions. The results show that the prevalence of CIDMO in our diabetic population was 0.5%. A significant proportion of macula oedema patients were found to have type 2 diabetes with long disease duration, suboptimal glycemic and hypertensive control, and low eGFR. The data support that medical and diabetic review of CIDMO patients is warranted particularly in the substantial number with poor glycemic control and if intravitreal therapies are indicated.

Proliferative diabetic retinopathy (R3) referrals from the digital diabetic retinopathy screening program:urgency of appointment in the hospital eye service achieved and needed?

DESIGN. Retrospective analysis PURPOSE. To assess the clinical characteristics and outcomes of patients identified with proliferative diabetic retinopathy (PDR) referred from the screening program to the hospital eye services (HES) METHODS. a retrospective analysis of urgently referred PDR cases to Birmingham Heartlands HES from august 2008 until July 2010 RESULTS. 130 urgent diabetic retinopathy referrals were made and reviewed. 103 (68% male, 80% type 2 diabetes) were referred for PDR with a mean age of 59 years, mean diabetes duration of 17.8years. 69% were on insulin treatment at the time of the screening, with mean HbA1c of 10.4% (range-5.7 to 16.5%). 65% of the patients were offered appointments at HES within two weeks after referral from the screening. 50.5% of the patients were seen in the HES within 2 weeks, 22 and 16 % were seen 2-4 and 4-8 weeks after referral respectively. 6 patients never attended ophthalmology examination during the two years of review. Of all the attendees, 56% were booked for pan retinal photocoagulation (PRP) & 9(9.3%) for macular laser respectively on their 1st HES visit. 75% of the patients were newly diagnosed PDR and 26 had previous PRP laser but lost to follow up. 63 patients ( 66%) received either PRP or macular laser treatment (85.7% of which is PRP). 63% of the PRP treatment was performed within a month of first HES attendance. Retinopathy grading discrepancy between the screening program and HES was noted in 20% (21 patients). CONCLUSIONS. This data suggests that the digital screening programme is appropriately identifying high risk patients with PDR with timely PRP laser treatment in the majority of patients but raises concern over patients lost to follow up (hence failsafe tracking of appointment attendance), and review of grading discrepancies between the ophthalmology and screening service.

Neurodegeneration is an early event in diabetic retinopathy:therapeutic implications

Diabetic retinopathy (DR) remains the leading cause of blindness among working-age individuals in developed countries. Current treatments for DR are indicated in advanced stages of the disease and are associated with significant adverse effects. Therefore, new pharmacological treatments for the early stages of DR are needed. DR has been classically considered to be a microcirculatory disease of the retina. However, there is growing evidence to suggest that retinal neurodegeneration is an early event in the pathogenesis of DR, which participates in the microcirculatory abnormalities that occur in DR. Therefore, the study of the underlying mechanisms that lead to neurodegeneration will be essential for identifying new therapeutic targets. From the clinical point of view, the identification of those patients in whom retinal neurodegeneration appears will be crucial for implementing early treatment based on neuroprotective drugs. When the early stages of DR are the therapeutic target, it would be inconceivable to recommend an aggressive treatment such as intravitreous injections. By contrast, topical administration of neuroprotective drugs by using eye drops is a possible option. However, clinical trials to determine the safety and effectiveness of this non-invasive route, as well as a standardisation of the methods for monitoring neurodegeneration, are needed.

Plasma vascular endothelial growth factor, angiopoietin-2, and soluble angiopoietin receptor tie-2 in diabetic retinopathy:effects of laser photocoagulation and angiotensin receptor blockade

Background: Proliferative diabetic retinopathy (PDR) may be a response to abnormal angiogenic growth factors such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), and the soluble angiopoietin receptor tie-2. The authors hypothesised the following: (a) there are differences in plasma levels of these growth factors in different grades of diabetic retinopathy; and (b) that the effects of intervention with panretinal laser photocoagulation (PRP) for PDR, and angiotensin receptor blockade (using eprosartan) for patients with other grades of diabetic retinopathy will be to reduce levels of the growth factors. Methods: Cross sectional and interventional study (using PRP and eprosartan) in diabetic patients. VEGF, Ang-2, and tie-2 were measured by ELISA. Results: VEGF (p<0.001) and Ang-2 levels (p<0.001) were significantly higher in 93 diabetic patients compared to 20 healthy controls, with the highest levels in grade 2 and grade 3 diabetic retinopathy (p<0.05). Tie-2 was lower in diabetics compared to controls (p = 0.008), with no significant differences between the diabetic subgroups. Overall, VEGF significantly correlated with Ang-2 (p<0.001) and tie-2 (p = 0.004) but the correlation between Ang-2 and tie-2 levels was not significant (p = 0.065). Among diabetic patients only, VEGF levels were significantly correlated with Ang-2 (p<0.001) and tie-2 (p<0.001); the correlation between Ang-2 and tie-2 levels was also significant (p<0.001). There were no statistically significant effects of laser photocoagulation on plasma VEGF, Ang-2, and tie-2 in the 19 patients with PDR, or any effects of eprosartan in the 28 patients with non-proliferative diabetic retinopathy. Conclusion: Increased plasma levels of VEGF and Ang-2, as well as lower soluble tie-2, were found in diabetic patients. The highest VEGF and Ang-2 levels were seen among patients with pre-proliferative and proliferative retinopathy, but there was no relation of tie-2 to the severity of retinopathy. As the majority of previous research into Ang-2 and tie-2 has been in relation to angiogenesis and malignancy, the present study would suggest that Ang-2 and tie-2 may be used as potential indices of angiogenesis in diabetes mellitus (in addition to VEGF) and may help elucidate the role of the angiopoietin/tie-2 system in this condition.

Grading and disease management in national screening for diabetic retinopathy in England and Wales

Aims - A National Screening Programme for diabetic eye disease in the UK is in development. We propose a grading and early disease management protocol to detect sight-threatening diabetic retinopathy and any retinopathy, which will allow precise quality assurance at all steps while minimizing false-positive referral to the hospital eye service. Methods - Expert panel structured discussions between 2000 and 2002 with review of existing evidence and grading classifications. Proposals - Principles of the protocol include: separate grading of retinopathy and maculopathy, minimum number of steps, compatible with central monitoring, expandable for established more complex systems and for research, no lesion counting, no ‘questionable’ lesions, attempt to detect focal exudative, diffuse and ischaemic maculopathy and fast track referral from primary or secondary graders. Sight-threatening diabetic retinopathy is defined as: preproliferative retinopathy or worse, sight-threatening maculopathy and/or the presence of photocoagulation. In the centrally reported minimum data set retinopathy is graded into four levels: none (R0), background (R1), preproliferative (R2), proliferative (R3). Maculopathy and photocoagulation are graded as absent (M0, P0) or present (M1, P1). Discussion - The protocol developed by the Diabetic Retinopathy Grading and Disease Management Working Party represents a new consensus upon which national guidelines can be based leading to the introduction of quality-assured screening for people with diabetes.

Diabetic retinopathy and blockade of the renin–angiotensin system:new data from the DIRECT study programme

The pathogenesis and medical management of diabetic retinopathy is reviewed. The importance of good control of blood glucose and blood pressure remain key elements in the prevention and treatment of diabetic retinopathy, and a number of specific metabolic pathways have been identified that may be useful additional targets for therapeutic intervention. Trial data, however, aimed specifically to answer the questions of optimum medical management are limited, so the DIRECT study of renin-angiotensin blockade using oral candesartan 32 mg daily is a welcome addition to our knowledge. This arose from the promising improvement of retinopathy outcomes in the EUCLID study of lisinopril in type I diabetes. In DIRECT, 5 years of candesartan treatment in type I diabetes reduced the incidence of retinopathy by two or more steps (EDTRS) in severity by 18% (P = 0.0508) and, in a post hoc analysis, reduced the incidence of retinopathy by three-step progression by 35% (P = 0.034). In type I diabetes patients there was no effect on progression of established retinopathy. In contrast, in type II diabetes, 5 years of candesartan treatment resulted in 34% regression of retinopathy (P ≤0.009). Importantly, an overall significant change towards less-severe retinopathy was noted in both type I and II diabetes (P0.03). Although there is still no absolute proof that these effects were specific to RAS blockade, or just an effect of lower blood pressure, it is reasonable to conclude that candesartan has earned a place in the medical management of diabetic retinopathy, to prevent the problem in type I diabetes and to treat the early stages in type II diabetes. © 2010 Macmillan Publishers Limited All rights reserved.

Diabetes : intravitreous ranibizumab for proliferative diabetic retinopathy

The Diabetic Retinopathy Clinical Research Network has published the 2-year results of a 5-year study comparing intravitreous ranibizumab with panretinal laser photocoagulation in patients with proliferative diabetic retinopathy. The results suggest that intravitreous ranibizumab will become a valuable treatment option, although its exact role remains to be defined.

Evaluating digital diabetic retinopathy screening in people aged 90 years and over

To evaluate the effectiveness of digital diabetic retinopathy screening in patients aged 90 years and over.MethodsThis is a retrospective analysis of 200 randomly selected patients eligible for diabetic retinopathy screening aged 90 years and over within the Birmingham, Solihull, and Black Country Screening Programme.ResultsOne hundred and seventy-nine (90%) patients attended screening at least once. 133 (74%) annual screening after their first screen, of whom 59% had no detectable diabetic retinopathy; 38 (21%) were referred for ophthalmology clinical assessment-36 for nondiabetic retinopathy reasons and two for diabetic maculopathy. Cataract accounted for 50% of all referrals for ophthalmology clinical assessment. Of the 133 patients placed on annual screening, 93 (70%) were screened at least once more. In terms of level of diabetic retinopathy, assessability or other ocular pathologies, 8 improved, 51 remained stable, and 31 deteriorated. Of the latter, 19 patients were referred for ophthalmology clinical assessment; none of these for diabetic retinopathy.ConclusionsScreening provides opportunistic identification of important nondiabetic retinopathy eye conditions. However, in view of the low identification rate of sight-threatening diabetic retinopathy in patients aged 90 years and over, and the current mission statement of the NHS Diabetic Eye Screening Programme, systematic annual diabetic retinopathy screening may not be justified in this age group of patients, but rather be performed in optometric practice.