Outreach screening to address demographic and economic barriers to diabetic retinopathy care in rural China.

IMPORTANCE: Poor access to existing care for diabetic retinopathy (DR) limits effectiveness of proven treatments. OBJECTIVES: We examined whether outreach screening in rural China improves equity of access. DESIGN, SETTING AND PARTICIPANTS: We compared prevalence of female sex, age > = 65 years, primary education or below, and requiring referral care for DR between three cohorts with diabetes examined for DR in neighboring areas of Guangdong, China: passive case detection at secondary-level hospitals (n = 193); persons screened during primary-level DR outreach (n = 182); and individuals with newly- or previously-diagnosed diabetes in a population survey (n = 579). The latter reflected the "ideal" reach of a screening program. RESULTS: Compared to the population cohort, passive case detection reached fewer women (50·8% vs. 62·3%, p = 0·006), older adults (37·8% vs. 51·3%, p < 0·001), and less-educated persons (39·9% vs. 89·6%, p < 0·001). Outreach screening, compared to passive case detection, improved representation of the elderly (49·5% vs. 37·8%, p = 0·03) and less-educated (70·3% vs. 39·9%, p<0·001). The proportion of women (59.8% vs 62.3%, P>0.300) and persons aged > = 65 years (49.5% vs 51.3%, p = 0.723) in the outreach screening and population cohorts did not differ significantly. Prevalence of requiring referral care for DR was significantly higher in the outreach screening cohort (28·0%) than the population (14·0%) and passive case detection cohorts (7·3%, p<0·001 for both). CONCLUSIONS AND RELEVANCE: Primary-level outreach screening improves access for the poorly-educated and elderly, and removes gender inequity in access to DR care in this setting, while also identifying more severely-affected patients than case finding in hospital.

Fundus Autofluorescence Imaging in Macular Telangiectasia Type 2: MacTel Study Report Number 9.

PURPOSE: To investigate the role of fundus autofluorescence (FAF) imaging in the diagnosis of macular telangiectasia type 2 (MacTel) and to describe disease-associated FAF patterns and their origin. DESIGN: Cross-sectional multicenter study METHODS: FAF images were collected from the multicenter MacTel Natural History Observation and Registry Study. In a first qualitative approach, common FAF phenotypes were defined and correlated with multimodal imaging. We then evaluated how many eyes showed FAF changes, and temporal vs nasal asymmetry of FAF changes was graded. Finally, 100 eyes of MacTel patients and 100 control eyes (50 normal eyes and 50 eyes with other macular diseases) were combined and 2 masked graders assessed the presence of MacTel based on FAF images alone. RESULTS: The study included 807 eyes of 420 patients (33 eyes were excluded owing to poor image quality). Loss of macular pigment, cystoid spaces, pigment plaques, neovascular membranes, and ectatic vascular changes commonly caused characteristic changes on FAF images. All MacTel patients had macular FAF changes in at least 1 eye. In 95% of eyes, these changes were more pronounced temporally than nasally. Common FAF patterns were increased (60%) and mixed/decreased FAF (38%) and/or visibility of vascular changes such as blunted vessels or ectatic capillaries (79%). Based on those features, high diagnostic performance was achieved for detection of the disease based on FAF alone (Youden index up to 0.91). CONCLUSIONS: The study demonstrates that MacTel is consistently associated with disease-specific changes on FAF imaging. Those changes are typically more pronounced in the temporal parafovea.

Quantification of Key Retinal Features in Early and Late Age-Related Macular Degeneration Using Deep Learning.

PURPOSE: We sought to develop and validate a deep learning model for segmentation of 13 features associated with neovascular and atrophic age-related macular degeneration (AMD). DESIGN: Development and validation of a deep-learning model for feature segmentation. METHODS: Data for model development were obtained from 307 optical coherence tomography volumes. Eight experienced graders manually delineated all abnormalities in 2712 B-scans. A deep neural network was trained with these data to perform voxel-level segmentation of the 13 most common abnormalities (features). For evaluation, 112 B-scans from 112 patients with a diagnosis of neovascular AMD were annotated by 4 independent observers. The main outcome measures were Dice score, intraclass correlation coefficient, and free-response receiver operating characteristic curve. RESULTS: On 11 of 13 features, the model obtained a mean Dice score of 0.63 ± 0.15, compared with 0.61 ± 0.17 for the observers. The mean intraclass correlation coefficient for the model was 0.66 ± 0.22, compared with 0.62 ± 0.21 for the observers. Two features were not evaluated quantitatively because of a lack of data. Free-response receiver operating characteristic analysis demonstrated that the model scored similar or higher sensitivity per false positives compared with the observers. CONCLUSIONS: The quality of the automatic segmentation matches that of experienced graders for most features, exceeding human performance for some features. The quantified parameters provided by the model can be used in the current clinical routine and open possibilities for further research into treatment response outside clinical trials.

United Kingdom Diabetic Retinopathy Electronic Medical Record (UK DR EMR) Users Group: report 4, real-world data on the impact of deprivation on the presentation of diabetic eye disease at hospital services.

AIM: To assess the impact of deprivation on diabetic retinopathy presentation and related treatment interventions, as observed within the UK hospital eye service. METHODS: This is a multicentre, national diabetic retinopathy database study with anonymised data extraction across 22 centres from an electronic medical record system. The following were the inclusion criteria: all patients with diabetes and a recorded, structured diabetic retinopathy grade. The minimum data set included, for baseline, age and Index of Multiple Deprivation, based on residential postcode; and for all time points, visual acuity, ETDRS grading of retinopathy and maculopathy, and interventions (laser, intravitreal therapies and surgery). The main  outcome measures were (1) visual acuity and binocular visual state, and (2) presence of sight-threatening complications and need for early treatment. RESULTS: 79 775 patients met the inclusion criteria. Deprivation was associated with later presentation in patients with diabetic eye disease: the OR of being sight-impaired at entry into the hospital eye service (defined as 6/18 to better than 3/60 in the better seeing eye) was 1.29 (95% CI 1.20 to 1.39) for the most deprived decile vs 0.77 (95% CI 0.70 to 0.86) for the least deprived decile; the OR for being severely sight-impaired (3/60 or worse in the better seeing eye) was 1.17 (95% CI 0.90 to 1.55) for the most deprived decile vs 0.88 (95% CI 0.61 to 1.27) for the least deprived decile (reference=fifth decile in all cases). There is also variation in sight-threatening complications at presentation and treatment undertaken: the least deprived deciles had lower chance of having a tractional retinal detachment (OR=0.48 and 0.58 for deciles 9 and 10, 95% CI 0.24 to 0.90 and 0.29 to 1.09, respectively); in terms of accessing treatment, the rate of having a vitrectomy was lowest in the most deprived cohort (OR=0.34, 95% CI 0.19 to 0.58). CONCLUSIONS: This large real-world study suggests that first presentation at a hospital eye clinic with visual loss or sight-threatening diabetic eye disease is associated with deprivation. These initial hospital visits represent the first opportunities to receive treatment and to formally engage with support services. Such patients are more likely to be sight-impaired or severely sight-impaired at presentation, and may need additional resources to engage with the hospital eye services over complex treatment schedules.

MACULAR TELANGIECTASIA TYPE 2: Quantitative Analysis of a Novel Phenotype and Implications for the Pathobiology of the Disease.

PURPOSE: To investigate retinal microcystoid spaces in macular telangiectasia type 2 with spectral domain optical coherence tomography. METHODS: Retrospective review of 135 patients enrolled in the MacTel Natural History Observation and Registry Study at Moorfields Eye Hospital, United Kingdom. One hundred seventy-two eyes from 86 patients who had a comparable scan protocol of at least 30 µm interval were included for analysis. Retinal microcystoid spaces were identified and segmented and metrics analyzed. RESULTS: From 172 eyes of 86 patients, microcystoid spaces were found in 11 eyes (6.4%) from 8 patients (9.3%). The mean number of microcystoid spaces per eye was 12.9 ± 18.2. Most were located in the inner nuclear layer. The inferonasal quadrant of the macula was the least commonly affected region. Microcystoid spaces were distributed entirely within the assumed macular telangiectasia area on blue light reflectance in all but 2 eyes (4 of 142 microcysts). The median diameter of the microcystoid spaces was 31 µm (range 15 µm-80 µm). CONCLUSION: Microcystoid spaces as a phenotype of macular telangiectasia should be considered in the differentials for microcystic edema. Understanding the pathogenesis of these lesions may provide further insight into the role of Müller cell dysfunction in this disorder.

The UK Diabetic Retinopathy Electronic Medical Record (UK DR EMR) Users Group, Report 2: real-world data for the impact of cataract surgery on diabetic macular oedema.

AIM: To assess the rate of 'treatment-requiring diabetic macular oedema (DMO)' in eyes for the two years before and after cataract surgery. METHODS: Multicentre national diabetic retinopathy (DR) database study with anonymised data extraction across 19 centres from an electronic medical record system. INCLUSION CRITERIA: eyes undergoing cataract surgery in patients with diabetes with no history of DMO prior to study start. The minimum dataset included: age, visual acuity (all time-points), injection episodes, timing of cataract surgery and ETDRS grading of retinopathy and maculopathy. MAIN OUTCOME MEASURE: rate of developing first episode of treatment-requiring DMO in relation to timing of cataract surgery in the same eye. RESULTS: 4850 eyes met the inclusion criteria. The rate of developing treatment-requiring DMO in this cohort was 2.9% in the year prior to surgery versus 5.3% in the year after surgery (p<0.01). The risk of 'treatment-requiring DMO' increased sharply after surgery, peaking in the 3-6 months' period (annualised rates of 5.2%, 6.8%, 5.6% and 4.0% for the 0-3, 3-6, 6-9 and 9-12 months' post-operative time periods respectively). Risk was associated with pre-operative grade of retinopathy: risk of DMO in the first year post-operatively being 1.0% (no DR pre-operatively), 5.4% (mild non-proliferative diabetic retinopathy; NPDR), 10.0% (moderate NPDR), 13.1% (severe NPDR) and 4.9% (PDR) (p<0.01). CONCLUSIONS: This large real-world study demonstrates that the rate of developing treatment-requiring DMO increases sharply in the year after cataract surgery for all grades of retinopathy, peaking in the 3-6 months' postoperative period. Patients with moderate and severe NPDR are at particularly high risk.

UK AMD/DR EMR REPORT IX: comparative effectiveness of predominantly as needed (PRN) ranibizumab versus continuous aflibercept in UK clinical practice.

AIMS: To compare the effectiveness of continuous aflibercept versus pro re nata (PRN) ranibizumab therapy for neovascular age-related macular degeneration (nAMD). METHODS: Multicentre, national electronic medical record (EMR) study on treatment naive nAMD eyes undergoing PRN ranibizumab or continuous (fixed or treat and extend (F/TE)) aflibercept from 21 UK hospitals. Anonymised data were extracted, and eyes were matched on age, gender, starting visual acuity (VA) and year of starting treatment. Primary outcome was change in vision at 1 year. RESULTS: 1884 eyes (942 eyes in each group) were included. At year 1, patients on PRN ranibizumab gained 1.6 ETDRS (Early Treatment Diabetic Retinopathy Study) letters (95% CI 0.5 to 2.7, p=0.004), while patients on F/TE aflibercept gained 6.1 letters (95% CI 5.1 to 7.1, p=2.2e-16). Change in vision at 1 year of the F/TE aflibercept group was 4.1 letters higher (95% CI 2.5 to 5.8, p=1.3e-06) compared with the PRN ranibizumab group after adjusting for age, starting VA, gender and year of starting therapy. The F/TE aflibercept group had significantly more injections compared with the PRN ranibizumab group (7.0 vs 5.8, p<2.2e-16), but required less clinic visits than the PRN ranibizumab group (10.8 vs 9.0, p<2.2e-16). Cost-effectiveness analysis showed an incremental cost-effectiveness ratio of 58 047.14 GBP/quality-adjusted life year for continuous aflibercept over PRN ranibizumab. CONCLUSION: Aflibercept achieved greater VA gains at 1 year than ranibizumab. The observed VA differences are small and likely to be related to more frequent treatment with aflibercept, suggesting that ranibizumab should also be delivered by F/TE posology.

Natural history and effect of therapeutic interventions on subretinal fluid causing foveal detachment in macular telangiectasia type 2.

AIM: To report the natural history of subretinal fluid (SRF) causing foveal detachment in macular telangiectasia type 2 (MacTel) and our experience of therapeutic intervention with intravitreal steroids or antivascular endothelial growth factor inhibitor (anti-VEGF) agents in some cases. METHODS: Retrospective case series. Three of the MacTel study's largest registries were searched to identify eyes with foveal detachment. RESULTS: We identified 7 eyes from 6 exclusively female patients. The prevalence of foveal detachment was low, present in 1.4% of the assessed MacTel population. Age at presentation ranged from 50 to 66 years. Follow-up ranged from 2 to 8 years. There was late-phase leakage on fluorescein angiography from what was presumed to be ectatic capillaries. The SRF fluctuated without a rapid decline in visual acuity in cases that were not treated. When they were, intravitreal anti-VEGF and steroid therapy in general reduced SRF, at least temporarily, but did not halt the gradual long-term decrease in visual acuity. In one case, optical coherence tomography angiography showed significant reduction in the extent of the predominantly deep intraretinal vascular complex 1 month after anti-VEGF therapy. DISCUSSION AND CONCLUSIONS: As the natural history of this unusual MacTel phenotype is not characterised by rapid visual decline, intervention with intravitreal anti-VEGF or steroid therapy may not be necessary.

UK Neovascular Age-Related Macular Degeneration Database. Report 6: time to retreatment after a pause in therapy. Outcomes from 92†976 intravitreal ranibizumab injections.

BACKGROUND/AIMS: To study the time to retreatment in eyes with neovascular age-related macular degeneration (nAMD) that had been treatment-free for intervals of 3 months, 6 months, 9 months and 12 months during the maintenance phase of ranibizumab therapy within the UK National Health Service. METHODS: In this multicentre national nAMD database study, structured data were collected from 14 centres (involving 12 951 eyes receiving 92 976 ranibizumab injections). Patients were treated with three fixed, monthly injections in a loading phase of treatment, followed by a pro re nata retreatment regimen in a maintenance phase. Eyes with a treatment-free interval (TFI) of 3 months, 6 months, 9 months or 12 months in the maintenance phase were identified and the time to retreatment after these TFIs was determined. RESULTS: The time to retreatment for the 20th and 50th centiles was 0.58/2.54 months after a 3-month TFI, 2.07/9.62 months after a 6-month TFI, 3.69/15.84 months after a 9-month TFI and 5.90/22.49 months after a 12-month TFI. Following a TFI of 3 months, 6 months, 9 months and 12 months, 68%, 44%, 31% and 21% of eyes required retreatments after an additional 6 months of follow-up, respectively. Similarly, after 12 months of follow-up, 77%, 56%, 43% and 34% of these eyes required retreatment. CONCLUSIONS: This study provides times to retreatment in eyes with nAMD that have been treatment-free for intervals of 3-12 months and demonstrates the likelihood of repeat therapy within the next year, even after a TFI of 12 months. These outcomes can help plan appropriate follow-up intervals for patients who have been treatment-free for intervals of up to 12 months.

The Evolution of Teleophthalmology Programs in the United Kingdom: Beyond Diabetic Retinopathy Screening.

Modern ophthalmic practice in the United Kingdom is faced by the challenges of an aging population, increasing prevalence of systemic pathologies with ophthalmic manifestations, and emergent treatments that are revolutionary but dependent on timely monitoring and diagnosis. This represents a huge strain not only on diagnostic services but also outpatient management and surveillance capacity. There is an urgent need for newer means of managing this surge in demand and the socioeconomic burden it places on the health care system. Concurrently, there have been exponential increases in computing power, expansions in the strength and ubiquity of communications technologies, and developments in imaging capabilities. Advances in imaging have been not only in terms of resolution, but also in terms of anatomical coverage, allowing new inferences to be made. In spite of this, image analysis techniques are still currently superseded by expert ophthalmologist interpretation. Teleophthalmology is therefore currently perfectly placed to face this urgent and immediate challenge of provision of optimal and expert care to remote and multiple patients over widespread geographical areas. This article reviews teleophthalmology programs currently deployed in the United Kingdom, focusing on diabetic eye care but also discussing glaucoma, emergency eye care, and other retinal diseases. We examined current programs and levels of evidence for their utility, and explored the relationships between screening, teleophthalmology, disease detection, and monitoring before discussing aspects of health economics pertinent to diabetic eye care. The use of teleophthalmology presents an immense opportunity to manage the steadily increasing demand for eye care, but challenges remain in the delivery of practical, viable, and clinically proven solutions.

Automated retinal image analysis for diabetic retinopathy in telemedicine.

There will be an estimated 552 million persons with diabetes globally by the year 2030. Over half of these individuals will develop diabetic retinopathy, representing a nearly insurmountable burden for providing diabetes eye care. Telemedicine programmes have the capability to distribute quality eye care to virtually any location and address the lack of access to ophthalmic services. In most programmes, there is currently a heavy reliance on specially trained retinal image graders, a resource in short supply worldwide. These factors necessitate an image grading automation process to increase the speed of retinal image evaluation while maintaining accuracy and cost effectiveness. Several automatic retinal image analysis systems designed for use in telemedicine have recently become commercially available. Such systems have the potential to substantially improve the manner by which diabetes eye care is delivered by providing automated real-time evaluation to expedite diagnosis and referral if required. Furthermore, integration with electronic medical records may allow a more accurate prognostication for individual patients and may provide predictive modelling of medical risk factors based on broad population data.

A randomized trial to assess functional and structural effects of ranibizumab versus laser in diabetic macular edema (the LUCIDATE study).

PURPOSE: To compare the functional and structural effects of ranibizumab versus macular laser therapy in patients with center-involving diabetic macular edema. DESIGN: Prospective, randomized, single-masked clinical trial. SETTING: Single center. STUDY POPULATION: Thirty-three eyes of 33 patients with center-involving diabetic macular edema, with best corrected visual acuity of 55 to 79 Early Treatment Diabetic Retinopathy Study letters at baseline, completing the 48-week study period. INTERVENTION: Subjects were randomized 2:1 to 3 loading doses of ranibizumab then retreatment every 4 weeks as required; or macular laser therapy at baseline, repeated as required every 12 weeks. Exploratory Outcome Measures: Structural imaging studies included greatest linear dimension and area of foveal avascular zone, perifoveal capillary dropout grade, and presence of morphologic features of diabetic macular edema on Spectralis optical coherence tomography (Heidelberg Engineering GmbH, Heidelberg, Germany). Functional measures: Visual acuity, retinal sensitivity in the central 4 and 12 degrees on microperimetry, color contrast sensitivity protan and tritan thresholds, pattern and full-field electroretinogram amplitudes and implicit times, and multifocal electroretinogram amplitude distribution. These were reported at 12, 24, and 48 weeks. RESULTS: Ranibizumab-treated subjects gained 6.0 vs 0.9 letters lost for laser, demonstrated improved tritan and protan color contrast thresholds, and improved retinal sensitivity. Electrophysiologic function also improved after ranibizumab therapy. No safety issues were evident. Better retinal thickness reduction and structural improvement in optical coherence tomography features of diabetic macular edema were seen with ranibizumab therapy than in the laser group. There was no evidence of progressive ischemia with ranibizumab therapy. CONCLUSIONS: Ranibizumab therapy in the treatment of diabetic macular edema seems to improve retinal function and structure as demonstrated by this evaluation of different assessment methods.

Clinical course and treatment outcomes of Sorsby fundus dystrophy.

PURPOSE: To analyze the natural history of Sorsby fundus dystrophy and the effect of various treatment methods for choroidal neovascularization (CNV) in this dystrophy. DESIGN: Historical cohort study. METHODS: A cohort of 42 patients with the Ser181 Cys TIMP3 mutation were identified from the electronic database of genetic retinal diseases in Moorfields Eye Hospital. Retrospective analyses of case records were carried out. Serial best-corrected visual acuity, fundus findings, age at onset of CNV, initial location of CNV, time taken for CNV to progress to subfoveal location, and the interval between development of CNV in the first and second eye were recorded. The time taken for CNV to recur to a subfoveal location in patients in whom argon laser photocoagulation was carried out for extrafoveal CNV also was documented. In cases where photodynamic therapy (PDT) was carried out for subfoveal CNV, the visual outcome, number of PDT treatments, and progression of lesion size were noted. RESULTS: The median age at onset of CNV in the first eye was 46.1 years and in the second eye was 50.3 years. The mean interval between the development of CNV in the first and second eye was 4.5 years. The median age at which vision fell to 20/200 or below was 48 years (first eye) and 54 years (second eye). Argon laser therapy and PDT are not effective in treating CNV of patients with this dystrophy. Antiangiogenic agents may be more effective in this condition. CONCLUSIONS: The main cause of blindness resulting from this dystrophy is CNV. Antiangiogenic agents may be useful in preventing visual loss as a result of this condition.