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.

Childhood-onset Leber hereditary optic neuropathy.

BACKGROUND: The onset of Leber hereditary optic neuropathy (LHON) is relatively rare in childhood. This study describes the clinical and molecular genetic features observed in this specific LHON subgroup. METHODS: Our retrospective study consisted of a UK paediatric LHON cohort of 27 patients and 69 additional cases identified from a systematic review of the literature. Patients were included if visual loss occurred at the age of 12 years or younger with a confirmed pathogenic mitochondrial DNA mutation: m.3460G>A, m.11778G>A or m.14484T>C. RESULTS: In the UK paediatric LHON cohort, three patterns of visual loss and progression were observed: (1) classical acute (17/27, 63%); (2) slowly progressive (4/27, 15%); and (3) insidious or subclinical (6/27, 22%). Diagnostic delays of 3-15 years occurred in children with an insidious mode of onset. Spontaneous visual recovery was more common in patients carrying the m.3460G>A and m.14484T>C mutations compared with the m.11778G>A mutation. Based a meta-analysis of 67 patients with available visual acuity data, 26 (39%) patients achieved a final best-corrected visual acuity (BCVA) ≥0.5 Snellen decimal in at least one eye, whereas 13 (19%) patients had a final BCVA <0.05 in their better seeing eye. CONCLUSIONS: Although childhood-onset LHON carries a relatively better visual prognosis, approximately 1 in 5 patients will remain within the visual acuity criteria for legal blindness in the UK. The clinical presentation can be insidious and LHON should be considered in the differential diagnosis when faced with a child with unexplained subnormal vision and optic disc pallor.

UK Age-Related Macular Degeneration Electronic Medical Record System (AMD EMR) Users Group Report IV: Incidence of Blindness and Sight Impairment in Ranibizumab-Treated Patients.

PURPOSE: To study the incidence of blindness and sight impairment in treatment-naive patients receiving ranibizumab (Lucentis) for neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) National Health Service. DESIGN: Multicenter nAMD database study. PARTICIPANTS: A total of 11 135 patients who collectively received 92 976 treatment episodes to 12 951 eyes. METHODS: Data were extracted from 14 UK centers using the same electronic medical record system (EMR). The EMR-mandated collection of a data set (defined before first data entry) including: age, Early Treatment Diabetic Retinopathy Study visual acuity letter score (VA) for both eyes at all visits, and injection episodes. Participating centers used overwhelmingly a pro re nata re-treatment posology at intended monthly follow-up visits following a loading phase of 3 monthly injections. MAIN OUTCOME MEASURES: Incidence of blindness and sight impairment (VA in the better-seeing eye <38 letters [≤20/200 Snellen, approximately], and <68 letters [≤20/50 Snellen, approximately] at 2 consecutive visits, or 1 visit if no further follow-up data) in each year after initiating treatment. RESULTS: Information from >300 000 clinic visits (2.8 million data points) collected over 5 years was collated from 14 centers. Mean age at first treatment was 79.7 years (standard deviation = 9.19 years), with a female preponderance (63%). The mean (median) VA at baseline in the better-seeing eye was 67.2 (72.0) letters, 20/40- (20/40+) approximate Snellen conversion. The cumulative incidence of new blindness and sight impairment in patients with treated nAMD in at least 1 eye at years 1 to 4 after first injection were 5.1%, 8.6%, 12% and 15.6% for new blindness and 29.6%, 41.0%, 48.7%, and 53.7% for new sight impairment, but with significant reductions in the rates between year cohorts initiating treatment (blindness [P = 4.72 × 10-08], sight impaired [P = 3.27 × 10-06]). CONCLUSIONS: To the best of our knowledge, this is the first multicenter real-world study on the incidence of blindness and sight impairment based on VA data in patients treated with ranibizumab for nAMD, and its results show low incidences of both blindness and sight impairment, which both declined during the study period.

UK AMD EMR USERS GROUP REPORT V: benefits of initiating ranibizumab therapy for neovascular AMD in eyes with vision better than 6/12.

BACKGROUND/AIMS: To study the effectiveness and clinical relevance of eyes treated with good (better than 6/12 or >70 Early Treatment Diabetic Retinopathy Study letters) visual acuity (VA) when initiating treatment with ranibizumab for neovascular age-related macular degeneration (nAMD) in the UK National Health Service. Currently eyes with VA better than (>) 6/12 are not routinely funded for therapy. METHODS: Multicentre national nAMD database study on patients treated 3-5 years prior to the analysis. Anonymised structured data were collected from 14 centres. The primary outcome was the mean VA at year 1, 2 and 3. Secondary measures included the number of clinic visits and injections. RESULTS: The study included 12 951 treatment-naive eyes of 11 135 patients receiving 92 976 ranibizumab treatment episodes. A total of 754 patients had baseline VA better than 6/12 and at least 1-year of follow up. Mean VA of first treated eyes with baseline VA>6/12 at year 1, 2, 3 were 6/10, 6/12, 6/15, respectively and those with baseline VA 6/12 to >6/24 were 6/15, 6/17, 6/20, respectively (p values <0.001 for comparing differences between 6/12 and 6/12-6/24 groups). For the second eyes with baseline VA>6/12, mean VA at year 1, 2, 3 were 6/9, 6/9, 6/10 and those with baseline VA 6/12 to >6/24 were 6/15, 6/15, 6/27, respectively (p values <0.001-0.005). There was no significant difference in the average number of clinic visits or injections between those with VA better and worse than 6/12. CONCLUSIONS: All eyes with baseline VA>6/12 maintained better mean VA than the eyes with baseline VA 6/12 to >6/24 at all time points for at least 2 years. The significantly better visual outcome in patients who were treated with good baseline VA has implications on future policy regarding the treatment criteria for nAMD patients' funding.

The neovascular age-related macular degeneration database: report 2: incidence, management, and visual outcomes of second treated eyes.

PURPOSE: To study the characteristics of second treated eyes in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab in the United Kingdom National Health Service. DESIGN: Multicenter national nAMD database study. PARTICIPANTS: Twelve thousand nine hundred fifty-one treatment-naïve eyes of 11,135 patients receiving 92,976 ranibizumab injections. METHODS: Up to 5 years of routinely collected, anonymized data within electronic medical record systems were extracted remotely from 14 centers. Participating centers exclusively used ranibizumab to treat nAMD (loading phase of 3 monthly injections followed by monthly visits and pro re nata re-treatment). The minimum data set included: age, logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) at baseline and at all subsequent visits, and injection episodes. MAIN OUTCOME MEASURES: Baseline, change and actual VA over 3 years, and number of treatments and clinic visits. RESULTS: During the study, 1816 (16.3%) of the 11 135 patients received treatment to the fellow eye. Mean baseline and final VA were 0.66 (standard deviation, 0.32) and 0.65 (0.40) for first treated eyes and 0.41 (0.34) and 0.56 (0.40) for second treated eyes. The rate of VA loss after the loading phase was similar in first and second treated eyes (0.03 and 0.05 logMAR units/year). When fellow eyes with baseline VA worse than 20/200 were excluded to restrict analyses to eyes at risk of nAMD, the rate of second-eye involvement was 14.0% per year (42%/3 years). Mean number of injections/visits in years 1, 2, and 3 were similar for first and second treated eyes (5.6/8.2, 3.9/8.0, 3.8/8.2 and 5.5/8.7, 3.6/9.4, and 3.8/9.1, respectively). CONCLUSIONS: Second treated eyes with nAMD commence treatment with better baseline VA, do not show significant vision gain but maintain better VA than first treated eyes at all time points for at least 3 years, making them the more important eye functionally. These data highlight the high burden of second eye involvement, with almost half of all eyes at risk requiring bilateral treatment by 3 years, and the need for regular monitoring of fellow eyes for best visual outcomes which theoretically may reduce the benefits of extended monitoring regimens.

Keratometry obtained by corneal mapping versus the IOLMaster in the prediction of postoperative refraction in routine cataract surgery.

BACKGROUND: To establish whether simulated keratometry values obtained by corneal mapping (videokeratography) would provide a superior refractive outcome to those obtained by Zeiss IOLMaster (partial coherence interferometry) in routine cataract surgery. DESIGN: Prospective, non-randomized, single-surgeon study set at the The Royal United Hospital, Bath, UK, District General Hospital. PARTICIPANTS: Thirty-three patients undergoing routine cataract surgery in the absence of significant ocular comorbidity. METHODS: Conventional biometry was recorded using the Zeiss IOLMaster. Postoperative refraction was calculated using the SRK/T formula and the most appropriate power of lens implanted. Preoperative keratometry values were also obtained using Humphrey Instruments Atlas Version A6 corneal mapping. MAIN OUTCOME MEASURES: Achieved refraction was compared with predicted refraction for the two methods of keratometry after the A-constants were optimized to obtain a mean arithmetic error of zero dioptres for each device. RESULTS: The mean absolute prediction error was 0.39 dioptres (standard deviation 0.29) for IOLMaster and 0.48 dioptres (standard deviation 0.31) for corneal mapping (P = 0.0015). Keratometry readings between the devices were highly correlated by Spearman correlation (0.97). The Bland-Altman plot demonstrated close agreement between keratometers, with a bias of 0.0079 dioptres and 95% limits of agreement of -0.48-0.49 dioptres. CONCLUSIONS: The IOLMaster was superior to Humphrey Atlas A6 corneal mapping in the prediction of postoperative refraction. This difference could not have been predicted from the keratometry readings alone. When comparing biometry devices, close agreement between readings should not be considered a substitute for actual postoperative refraction data.

Optimization of biometry for intraocular lens implantation using the Zeiss IOLMaster.

PURPOSE: To compare the accuracy of biometry using conventional A-scan ultrasonography and partial coherence interferometry, and to improve the accuracy of biometry by sequential audit of postoperative refractive error. METHODS: The study was performed in three phases. In phase 1, 20 consecutive patients undergoing routine phacoemulsification underwent biometry using both A-scan ultrasonography and the Zeiss IOLMaster (ZIOLM). A single experienced optometrist refracted all patients 2 weeks after surgery. The errors between expected and achieved refraction were calculated and compared between the two methods. In phases 2 and 3, a further 22 and 20 patients, respectively, were recruited and only the ZIOLM was used for biometry. The manufacturer's suggested A-constant was refined and the error between expected and achieved refraction was calculated. RESULTS: In phase 1, the median unexpected error for the ZIOLM was +0.63 (interquartile range +0.368 to +1.015) and for A-scan biometry was - 0.24 (interquartile range - 1.335 to +0.802). In phase 1 65% of patients' postoperative refractions were found to be within 1.0 D of emmetropia using the ZIOLM (55% using A-scan biometry). Refinements to the A-constant improved this to 95% by phase 3. CONCLUSION: An error was identified in IOL power estimation with the ZIOLM, when using the manufacturer's recommended A-constant (recommended and previously optimized ultrasound A-constant 118.0; ZIOLM optimized A-constant 118.6). Serial modifications to the A-constant were successful in reducing the unexpected error to well within the tolerance limits of published international standards.

Optimization of biometry for intraocular lens implantation using the Zeiss IOLMaster.

PURPOSE: To compare the accuracy of biometry using conventional A-scan ultrasonography and partial coherence interferometry, and to improve the accuracy of biometry by sequential audit of postoperative refractive error. METHODS: The study was performed in three phases. In phase 1, 20 consecutive patients undergoing routine phacoemulsification underwent biometry using both A-scan ultrasonography and the Zeiss IOLMaster (ZIOLM). A single experienced optometrist refracted all patients 2 weeks after surgery. The errors between expected and achieved refraction were calculated and compared between the two methods. In phases 2 and 3, a further 22 and 20 patients, respectively, were recruited and only the ZIOLM was used for biometry. The manufacturer's suggested A-constant was refined and the error between expected and achieved refraction was calculated. RESULTS: In phase 1, the median unexpected error for the ZIOLM was+0.63 (interquartile range+0.368 to+1.015) and for A-scan biometry was --0.24 (interquartile range--1.335 to+0.802). In phase 1 65% of patients' postoperative refractions were found to be within 1.0 D of emmetropia using the ZIOLM (55% using A-scan biometry). Refinements to the A-constant improved this to 95% by phase 3. CONCLUSION: An error was identified in IOL power estimation with the ZIOLM, when using the manufacturer's recommended A-constant (recommended and previously optimized ultrasound A-constant 118.0; ZIOLM optimized A-constant 118.6). Serial modifications to the A-constant were successful in reducing the unexpected error to well within the tolerance limits of published international standards.

Human retinal molecular weight exclusion limit and estimate of species variation.

PURPOSE: To determine the maximum size of molecule capable of freely diffusing across human retina, referred to as the retinal exclusion limit (REL), and the location of any sites of high resistance to diffusion. To assess the degree of interspecies variation in the REL of three animals commonly used to model human disease. METHODS: Trephines of human neuroretina were mounted in a modified Ussing chamber. FITC-dextrans of various molecular weights (MWT) were dissolved in phosphate-buffered saline, and the rate of transretinal diffusion was determined over 24 hours with a spectrophotometer. The theoretical REL was calculated by extrapolating the linear relationship between the rate of diffusion and log(MWT). In separate experiments to determine the sites of barrier to diffusion, FITC-dextrans with a MWT greater than the calculated REL were applied to either the inner or outer retinal surface, processed as frozen sections, and viewed with a fluorescence microscope. Experiments to determine the REL were repeated in bovine, porcine, and rabbit retina. RESULTS: The REL in human tissue was 76.5+/-1.5 kDa (6.11+/-0.04 nm). The inner and outer plexiform layers formed the sites of highest resistance to diffusion. The REL in pigs, cattle, and rabbits were 60 +/- 11.5, 78.5 +/- 20.5, and 86 +/- 30 kDa, respectively (5.68 +/- 0.45, 6.18 +/- 0.61, and 6.38 +/- 0.88 nm). CONCLUSIONS: In humans, the inner and outer plexiform layers are sites of high resistance to the diffusion of large molecules, resulting in an REL of 76.5 kDa. There was only moderate interspecies variation in the REL of the animals studied, suggesting that they provide adequate models for the study of human transretinal macromolecular diffusion.