25th RCOphth Congress, President's Session paper:25 years of progress in medical retina

The quarter century since the foundation of the Royal College of Ophthalmologists has coincided with immense change in the subspecialty of medical retina, which has moved from being the province of a few dedicated enthusiasts to being an integral, core part of ophthalmology in every eye department. In age-related macular degeneration, there has been a move away from targeted, destructive laser therapy, dependent on fluorescein angiography to intravitreal injection therapy of anti-growth factor agents, largely guided by optical coherence tomography. As a result of these changes, ophthalmologists have witnessed a marked improvement in visual outcomes for their patients with wet age-related macular degeneration (AMD), while at the same time developing and enacting entirely novel ways of delivering care. In the field of diabetic retinopathy, this period also saw advances in laser technology and a move away from highly destructive laser photocoagulation treatment to gentler retinal laser treatments. The introduction of intravitreal therapies, both steroids and anti-growth factor agents, has further advanced the treatment of diabetic macular oedema. This era has also seen in the United Kingdom the introduction of a coordinated national diabetic retinopathy screening programme, which offers an increasing hope that the burden of blindness from diabetic eye disease can be lessened. Exciting future advances in retinal imaging, genetics, and pharmacology will allow us to further improve outcomes for our patients and for ophthalmologists specialising in medical retina, the future looks very exciting but increasingly busy.

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.

Improving the cost-effectiveness of photographic screening for diabetic macular oedema:a prospective, multi-centre, UK study

Background/aims: Retinal screening programmes in England and Scotland have similar photographic grading schemes for background (non-proliferative) and proliferative diabetic retinopathy, but diverge over maculopathy. We looked for the most cost-effective method of identifying diabetic macular oedema from retinal photographs including the role of automated grading and optical coherence tomography, a technology that directly visualises oedema. Methods: Patients from seven UK centres were recruited. The following features in at least one eye were required for enrolment: microaneurysms/dot haemorrhages or blot haemorrhages within one disc diameter, or exudates within one or two disc diameters of the centre of the macula. Subjects had optical coherence tomography and digital photography. Manual and automated grading schemes were evaluated. Costs and QALYs were modelled using microsimulation techniques. Results: 3540 patients were recruited, 3170 were analysed. For diabetic macular oedema, England's scheme had a sensitivity of 72.6% and specificity of 66.8%; Scotland 's had a sensitivity of 59.5% and specificity of 79.0%. When applying a ceiling ratio of £30 000 per quality adjusted life years (QALY) gained, Scotland's scheme was preferred. Assuming automated grading could be implemented without increasing grading costs, automation produced a greater number of QALYS for a lower cost than England's scheme, but was not cost effective, at the study's operating point, compared with Scotland's. The addition of optical coherence tomography, to each scheme, resulted in cost savings without reducing health benefits. Conclusions: Retinal screening programmes in the UK should reconsider the screening pathway to make best use of existing and new technologies.

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.

Improving the economic value of photographic screening for optical coherence tomography-detectable macular oedema:a prospective, multicentre, UK study

Objectives: To determine the best photographic surrogate markers for detecting sight-threatening macular oedema (MO) in people with diabetes attending UK national screening programmes. Design: A multicentre, prospective, observational cohort study of 3170 patients with photographic signs of diabetic retinopathy visible within the macular region [exudates within two disc diameters, microaneurysms/dot haemorrhages (M/DHs) and blot haemorrhages (BHs)] who were recruited from seven study centres. Setting: All patients were recruited and imaged at one of seven study centres in Aberdeen, Birmingham, Dundee, Dunfermline, Edinburgh, Liverpool and Oxford. Participants: Subjects with features of diabetic retinopathy visible within the macular region attending one of seven diabetic retinal screening programmes. Interventions: Alternative referral criteria for suspected MO based on photographic surrogate markers; an optical coherence tomographic examination in addition to the standard digital retinal photograph. Main outcome measures: (1) To determine the best method to detect sight-threatening MO in people with diabetes using photographic surrogate markers. (2) Sensitivity and specificity estimates to assess the costs and consequences of using alternative strategies. (3) Modelled long-term costs and quality-adjusted life-years (QALYs). Results: Prevalence of MO was strongly related to the presence of lesions and was roughly five times higher in subjects with exudates or BHs or more than two M/DHs within one disc diameter. Having worse visual acuity was associated with about a fivefold higher prevalence of MO. Current manual screening grading schemes that ignore visual acuity or the presence of M/DHs could be improved by taking these into account. Health service costs increase substantially with more sensitive/less specific strategies. A fully automated strategy, using the automated detection of patterns of photographic surrogate markers, is superior to all current manual grading schemes for detecting MO in people with diabetes. The addition of optical coherence tomography (OCT) to each strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. Conclusions: Compared with all current manual grading schemes, for the same sensitivity, a fully automated strategy, using the automated detection of patterns of photographic surrogate markers, achieves a higher specificity for detecting MO in people with diabetes, especially if visual acuity is included in the automated strategy. Overall, costs to the health service are likely to increase if more sensitive referral strategies are adopted over more specific screening strategies for MO, for only very small gains in QALYs. The addition of OCT to each screening strategy, prior to referral, results in a reduction in costs to the health service with no decrement in the number of MO cases detected. © Queen's Printer and Controller of HMSO 2013.

Is it safe to increase diabetic retinopathy screening intervals in patients with no/background diabetic retinopathy?

Patients who present with background DR should continue to be screened annually as a high prportion of these patients develop sight threatening DR (12%). A low prportion of patients with no DR at baseline were referred for STDR (1.3%). Out of the 51 patients in this category referred only 1 required laser. The authors suggest that patients graded R0M0 could be screened biannually.

Is it safe to increase diabetic retinopathy screening intervals in patients with no background diabetic retinopathy?

Introduction. A 4 year retrospective follow up of 996 patients who pre-sented with no DR and 500 with background DR at baseline digital DR screening in 2006. Purpose. To evaluate the safety of increasing screening intervals in patients with no diabetic retinopathy (DR) or with background DR.Methods. A 4 year retrospective follow up of 996 patients who presented with no DR and 500 with background DR at baseline digital DR screening in 2006.results. Background DR Group: Of the 500 subjects that had back-ground DR in 2006, 231 were referred for DR, with an average DR routine referral rate of 12% (46 subjects) per year. nodrgrouP. Of the 996 patients who had no DR at baseline, 51 were referred over the 4 years for sight threatening DR (STDR), of these 45 patients have definite STDR confirmed by ophthalmological examination. 78% of these had type 2 diabetes and mean age at referral was 60 years (25-87). Mean diabetes duration was 10.7 years (3-32), with a mean HbA1c of 7.8% (5.7-11.3%). Eight patients (0.9%) were referred in the first year, 9 (0.9%) in the second year, 19 (1.9%) in the third year and 15 (1.5%) in the fourth year. 86% of referrals were for maculopathy, and all had observable retinopathy and none required ophthalmology clinic assessment or laser treatment.If biannual screening was adopted for patients with no DR at baseline, allowing for patients who subsequently develop background DR and would then revert to annual screening, a total of 7 (0.7%) patients would not have been appropriately referred for STDR and would have waited a further year for identification. None of the 51 referrals across the 4 years required laser treatment apart from just one patient who developed PDR in year 4 (2010) and had background since 2007.conclusIons. It could be recommended that it is safe to screen pa-tients with no DR biannually due to the low risk of developing STDR. However, patients who present with background DR should continue to be screened annually as there is a significant proportion developing STDR and would not be identified at an appropriate screening interval.

Reply: 'Myopic foveoschisis: An ectatic retinopathy, not a schisis'

Full text: We thank Tsilimbaris et al1 for their comments on the appropriateness of the term ‘myopic foveoschisis’ to describe the condition that is characterized by the separation of neural retina layers associated with high myopia and posterior staphyloma. They have proposed the term ‘myopic ectatic retinopathy’ as a more literal and functionally more accurate descriptor of the condition to avoid the use of the word ‘schisis’, which may be misleading because it is also used to describe other conditions where there is separation of neural retina layers without the presence of staphyloma.2 Using the word ‘ectatic’ for this condition would imply that we are fairly certain about the pathogenesis and mechanistic factors that underlie its development and progression. However, this is not the case, unfortunately, as our review of the literature has shown. There are several theories ranging from vitreous traction to sclerosing changes of retinal vessels to progression of staphylomas as possible etiological factors. Therefore, it is likely to be multifactorial in nature—hence the success reported with different procedures that address either the vitreous traction factor using vitrectomy, peel plus tamponade or the scleral ectasia factor using posterior buckling techniques. In the absence of a good understanding of underlying pathogenesis, it is probably best to use purely descriptive names rather than mechanistic terms. The use of descriptive terms, even though similar, do not necessarily cause confusion as long as they are widely accepted as differentiating terminology, for example, postoperative pseudophakic cystoid macular edema (Irvine–Gass syndrome) vs cystoid macular edema associated with posterior uveitis in a phakic patient. The introduction of too many mechanistic or pathogenetic terms in the absence of clear understating of etiology can in fact cause more confusion, for example, serous chorioretinopathy vs central serous retinopathy vs serous choroidopathy. The confinement to broad descriptive terms can enhance communication and reduce confusion without committing to any presumption about etiology until it is better understood. This approach is probably best illustrated by the recent advances in the understanding of mactel21, a condition initially described and classified, using descriptive nomenclature, by Don Gass as bilateral, idiopathic acquired juxtafoveolar telangiectasis (Group2A) and as distinctly different from unilateral, congenital parafoveolar telangiectasis (Group 1A; Gass,3 pp 504–506 vs 127–128). Finally, it is worthy to note that for myopic foveoschisis associated with a staphyloma that is associated with outer layer macular detachment, Don Gass also descriptively included the additional observation (before the advent of OCT) that the retinal profile was concave rather than convex in shape, thereby differentiating it from rhegmatogenous detachments with recruitment of subretinal fluid that is associated with posteriorly located breaks and macular holes in myopic eyes. References 1.Tsilimbaris MK, Vavvas DG, Bechrakis NE. Myopic foveoschisis: an ectatic retinopathy, not aschisis. Eye 2016; 30: 328–329. 2.Powner MB, Gillies MC, Tretiach M, Scott A, Guymer RH, Hageman GS et al. Perifoveal müller cell depletion in a case of macular telangiectasia type 2. Ophthalmology 2010; 117(12): 2407–2416. 3.Gass DM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment, 4th edn. Mosby-Yearbook: St. Louis, 1997.

Enhancing the Visualization of the Peripheral Retina with Wide Field-of-View Optical Coherence Tomography

The goal of my Ph.D. thesis is to enhance the visualization of the peripheral retina using wide-field optical coherence tomography (OCT) in a clinical setting.

OCT has gain widespread adoption in clinical ophthalmology due to its ability to visualize the diseases of the macula and central retina in three-dimensions, however, clinical OCT has a limited field-of-view of 300. There has been increasing interest to obtain high-resolution images outside of this narrow field-of-view, because three-dimensional imaging of the peripheral retina may prove to be important in the early detection of neurodegenerative diseases, such as Alzheimer's and dementia, and the monitoring of known ocular diseases, such as diabetic retinopathy, retinal vein occlusions, and choroid masses.

Before attempting to build a wide-field OCT system, we need to better understand the peripheral optics of the human eye. Shack-Hartmann wavefront sensors are commonly used tools for measuring the optical imperfections of the eye, but their acquisition speed is limited by their underlying camera hardware. The first aim of my thesis research is to create a fast method of ocular wavefront sensing such that we can measure the wavefront aberrations at numerous points across a wide visual field. In order to address aim one, we will develop a sparse Zernike reconstruction technique (SPARZER) that will enable Shack-Hartmann wavefront sensors to use as little as 1/10th of the data that would normally be required for an accurate wavefront reading. If less data needs to be acquired, then we can increase the speed at which wavefronts can be recorded.

For my second aim, we will create a sophisticated optical model that reproduces the measured aberrations of the human eye. If we know how the average eye's optics distort light, then we can engineer ophthalmic imaging systems that preemptively cancel inherent ocular aberrations. This invention will help the retinal imaging community to design systems that are capable of acquiring high resolution images across a wide visual field. The proposed model eye is also of interest to the field of vision science as it aids in the study of how anatomy affects visual performance in the peripheral retina.

Using the optical model from aim two, we will design and reduce to practice a clinical OCT system that is capable of imaging a large (800) field-of-view with enhanced visualization of the peripheral retina. A key aspect of this third and final aim is to make the imaging system compatible with standard clinical practices. To this end, we will incorporate sensorless adaptive optics in order to correct the inter- and intra- patient variability in ophthalmic aberrations. Sensorless adaptive optics will improve both the brightness (signal) and clarity (resolution) of features in the peripheral retina without affecting the size of the imaging system.

The proposed work should not only be a noteworthy contribution to the ophthalmic and engineering communities, but it should strengthen our existing collaborations with the Duke Eye Center by advancing their capability to diagnose pathologies of the peripheral retinal.

Trends in blindness due to diabetic retinopathy among adults aged 18-69 years over a decade in Ireland

Aims: To describe trends in the incidence of visual impairment and blindness due to diabetic retinopathy among adults aged 18–69 years in Ireland between 2004 and 2013. Methods: Data on visual impairment due to diabetic retinopathy in adults aged 18–69 years or over who are registered with the National Council for the Blind of Ireland, (2004–2013) were analysed. Annual incidence rates were calculated for the adult population and the population with diagnosed diabetes. Poisson regression was used to test for changes in rates over time. The relative, attributable and population risk of blindness and visual impairment due to diabetic retinopathy were calculated for 2013. Results: Over the decade, the prevalence of diagnosed diabetes increased from 2.1% to 3.6%. Among people with diagnosed diabetes, the incidence of visual impairment due to diabetic retinopathy increased from 6.4 (95% CI 2.4–13.9) per 100,000 in 2004 to 11.7 (95% CI 5.9–21.0) per 100,000 in 2013. The incidence of blindness due to diabetic retinopathy varied from 31.9 per 100,000 (95% CI 21.6–45.7) in 2004 to 14.9 per 100,000 (95% CI 8.2–25.1) in 2013. Conclusions: Our findings indicate the need for increased attention to preventive measures for microvascular complications among adults with diabetes in Ireland. Retinopathy screening has been standardised in Ireland, these findings provide useful baseline statistics to monitor the impact of this population-based screening programme.

Epidemiology of diabetes and complications among adults in the Republic of Ireland 1998-2015: a systematic review and meta-analysis

Background: Accurate estimates of the burden of diabetes are essential for future planning and evaluation of services. In Ireland, there is no diabetes register and prevalence estimates vary. The aim of this review was to systematically identify and review studies reporting the prevalence of diabetes and complications among adults in Ireland between 1998 and 2015 and to examine trends in prevalence over time. Methods: A systematic literature search was carried out using PubMed and Embase. Diabetes prevalence estimates were pooled by random-effects meta-analysis. Poisson regression was carried out using data from four nationally representative studies to calculate prevalence rates of doctor diagnosed diabetes between 1998 and 2015 and was also used to assess whether the rate of doctor diagnosed diabetes changed over time. Results: Fifteen studies (eight diabetes prevalence and seven complication prevalence) were eligible for inclusion. In adults aged 18 years and over, the national prevalence of doctor diagnosed diabetes significantly increased from 2.2 % in 1998 to 5.2 % in 2015 (p trend ≤ 0.001). The prevalence of diabetes complications ranged widely depending on study population and methodology used (6.5–25.2 % retinopathy; 3.2–32.0 % neuropathy; 2.5-5.2 % nephropathy). Conclusions: Between 1998 and 2015, there was a significant increase in the prevalence of doctor diagnosed diabetes among adults in Ireland. Trends in microvascular and macrovascular complications prevalence could not be examined due to heterogeneity between studies and the limited availability of data. Reliable baseline data are needed to monitor improvements in care over time at a national level. A comprehensive national diabetes register is urgently needed in Ireland.

HELLP Syndrome a Severe Form of Preeclampsia: a Comparative Study of Clinical and Laboratorial Parameters

The objective of this study was to compare clinical, laboratorial, maternal and perinatal results between HELLP Syndrome and severe Preeclampsia. An observational study comparing women with HELLP Syndrome (n=71) to women with severe preeclampsia (n=253) was done. The authors analyzed the early course of the pathologies and the outcomes in both groups. HELLP syndrome occurred in 28% of all the cases and was more frequent at gestational age before 32 weeks (n=39 – 55%) than severe preeclampsia (n=108 - 42%), with more newborns weighting less than 1500g (27 – 38.6% vs 65 – 25.6%; p=0.036). Thrombocytopenia below 100 000/μL (aOR, 2.14; 95% CI, 1.49 – 3.06) and LDH>1 000 UI/L (aOR: 5.17; 95% CI 2.19 – 12.16) were risk factors for HELLP. Maternal morbidity (eclampsia, abruptio placentae, and acute renal failure) was similar in both cohorts; eight stillbirths (6 in severe preeclampsia and 2 in HELLP Syndrome) occurred. There were no maternal deaths. In conclusion, in this study the authors confirmed that HELLP Syndrome is a severe form of preeclampsia with an earlier presentation in pregnancy, worst laboratorial findings and more prematurity rates.

Purtscher-like retinopathy

Purtscher-like retinopathy is associated with retinal hemorrhages and ischaemia probably due to the complement-mediated leukoembolization. It is a rare and severe angiopathy found in conditions such as acute pancreatitis. Case. We present a case of a 53-year-old man who presented with a Purtscher-like retinopathy associated with the development of acute pancreatitis in the context of a Klatskin tumour (a hilar cholangiocarcinoma). The ophthalmologic evaluation revealed the best corrected visual acuity (BCVA) of 20/32 in the right eye (RE) and of 20/40 in the left eye (LE); biomicroscopy of anterior segment showed scleral icterus and fundoscopy revealed peripapillary cotton-wool spots, optic disc edema, and RPE hypo- and hyperpigmentation in the middle peripheral retina in both eyes with an intraretinal hemorrhage in the LE. 15 months after the initial presentation, without ophthalmological treatment, there was an improvement of BCVA to 20/20 in both eyes and optical coherence tomography (OCT) revealed areas of reduction of retinal nerve fiber layer thickness corresponding to the previous cotton-wool spots. Conclusion. Purtscher-like retinopathy should not be neglected in complex clinical contexts. Its unclear pathophysiology determines an uncertain treatment strategy, but a meticulous follow-up is compulsory in order to avoid its severe complications.

Use of GLP-1 mimetic in type 2 diabetes mellitus: is it the end of fragility fractures?

International audience

Comparison of Complications and Efficacy of NIPPV and Nasal CPAP in Preterm Infants With RDS

Background: Respiratory distress syndrome (RDS) is one of the most common diseases in neonates admitted to NICU. For this important cause of morbidity and mortality in preterm neonates, several treatment methods have been used. To date, non-invasive methods are preferred due to fewer complications. Objectives: Herein, two non-invasive methods of ventilation support are compared: NCPAP vs. NIPPV. Patients and Methods: This is a randomized clinical trial. Premature neonates with less than 34 weeks gestation, suffering from RDS entered the study, including 151 newborns admitted to Vali-Asr NICU during 2012-2013. Most of these patients received surfactant as early rescue via INSURE method and then randomly divided into two NCPAP (73 neonates) and NIPPV (78 neonates) groups. Both early and late complications are compared including extubation failure, hospital length of stay, GI perforation, apnea, intraventricular hemorrhage (IVH) and mortality rate. Results: The need for re-intubation was 6% in NIPPV vs. 17.6% in NCPAP group, which was statistically significant (P = 0.031). The length of hospital stay was 23.92 ± 13.5 vs. 32.61 ± 21.07 days in NIPPV and NCPAP groups, respectively (P = 0.002). Chronic lung disease (CLD) was reported to be 4% in NCPAP and 0% in NIPPV groups (P = 0.035). The most common complication occurred in both groups was traumatization of nasal skin and mucosa, all of which fully recovered. Gastrointestinal perforation was not reported in either group. Conclusions: This study reveals the hospital length of stay, re-intubation and BPD rates are significantly declined in neonates receiving NIPPV as the treatment for RDS.