Patient-Reported Outcome Measures (PROMs) with Refractive and Diffractive Extended Depth of Focus (EDOF) Intraocular Lenses.

BACKGROUND: Extended depth of focus intraocular lenses (EDOF-IOLs) provide unaided far- and mid-range vision. Refractive IOLs, in contrast to diffractive designs, are associated with a lower depth of focus and absence of dysphotopsia. The aim of this study was to assess spectacle independence for far-range, mid-range, and near-vision activities in patients after implantation of refractive or diffractive EDOF-IOLs using patient-reported outcome measures (PROMs) in a real-world setting. PATIENTS AND METHODS: In 2021 and 2022, all patients in a single center referred for bilateral cataract surgery were assigned to 7 experienced cataract surgeons who either bilaterally implanted only a diffractive EDOF-IOL (Carl Zeiss Meditec AG, AT LARA Jena, Germany, three surgeons) or refractive EDOF-IOL (Johnson & Johnson Vision Inc., Tecnis Eyhance Irvine, California, USA, four surgeons) at the surgeon's discretion, with the aim of bilateral emmetropia. Six months after both cataract surgeries, all patients were contacted by telephone and asked to report their outcomes using a structured questionnaire investigating their spectacle usage for various daily activities and their experience with night glare or halos. Inclusion criteria were a normal postoperative visual potential based on the preoperative examination and completion of the questionnaire regarding postoperative visual experience. RESULTS: Of the patients, 514 underwent bilateral cataract surgery aiming for bilateral emmetropia with the implantation of EDOF-IOLs (422 with Tecnis Eyhance and 92 with AT LARA). A complete questionnaire was obtained from 472 (92%) patients, who were included in the study (393 vs. 79). Comparing Tecnis Eyhance with AT LARA IOL, 54 vs. 57% patients were able to perform most of their daily activities without spectacles, 9 vs. 19% reported not being dependent on spectacles at all, 25 vs. 29% reported using their smartphones without spectacles, 15 vs. 49% patients reported experiencing glares or halos at night, and 1 vs.15% with driving disturbance. Overall, 95 vs. 93% patients described themselves as "satisfied" or "highly satisfied" with their IOL. CONCLUSIONS: With both types of EDOF-IOLs, the majority of patients could perform most of their daily activities without spectacles, except reading, and were highly satisfied with their IOLs. Patients with diffractive Zeiss AT LARA EDOF-IOLs were more likely to accomplish unaided near-range visual tasks; however, they were also at a higher risk of experiencing glares or halos at night.

Use of Spectacles after Cataract Surgery.

PURPOSE: The goal of this study was to investigate the use of spectacles in everyday life after bilateral cataract surgery with a preoperative refractive target of emmetropia in both eyes. In addition, we analyzed the total cost of spectacles and the patient's visual satisfaction at least 6 months after surgery. METHODS: Patients after bilateral cataract surgery with implantation of an aspheric monofocal IOL (Tecnis 1, Johnson & Johnson) with a preoperative refractive target of emmetropia in both eyes and a documented refractive outcome were included in this prospective observational study. In a phone interview ≥ 6 months after surgery, the following items were assessed: type of spectacles purchased and overall cost, type of activity with and duration of spectacle wear, and satisfaction with the visual situation. RESULTS: Seventy patients were included in this study. Depending on their postoperative refraction, patients were divided into group A (n = 27) with perfect emmetropia in both eyes (i.e., spherical equivalent [SE] of ≥ - 0.25 D to ≤ + 0.25 D), group B (n = 21) with achieved emmetropia in one eye (i.e., SE of ≥ - 0.25 D to ≤ + 0.25 D) and a myopic refraction in the other eye (< - 0.25 D), and group C (n = 22) with bilateral myopic results (SE of < - 0.25 D). Overall, 84% of patients had purchased new spectacles, mostly varifocals (59%) or reading glasses (24%) at the median cost of 980 Swiss Francs (mean: CHF 912 ± 746). Despite patients' initial reasoning for their lens choice to require reading glasses only, varifocal glasses were worn for more than 50% or all of awake time by 48% of patients in group A, 43% in group B, and 68% in group C. Despite their regular spectacles use, patients' visual satisfaction was very high in all three groups. CONCLUSIONS: Most patients who achieve perfect bilateral emmetropia after implantation of monofocal aspheric lenses buy varifocal spectacles within 6 months, and more than half of all patients use their varifocal spectacles for more than 50% of their awakening time. The costs for such spectacles are high.

Emergency Vitrectomies for Retinal Detachment Before and During the Coronavirus Pandemic - A Retrospective Single Centre Analysis.

BACKGROUND: While the corona pandemic and the resulting containment measures affect the number of elective surgical procedures, the impact on emergency surgical interventions is less tangible. This analysis quantifies the frequency of emergency vitrectomies for retinal detachment and investigates underlying factors. METHODS: Retrospective identification of patients who underwent primary emergency vitrectomies for retinal detachment at the Cantonal Hospital of Lucerne between 01.01.2018 - 31.12.2020. Parameters were collected, including demographics, date of hospitalisation, reported onset of symptoms, pre-operative best corrected visual acuity (BCVA), involvement of the macula, and canton of residence. RESULTS: Overall, a total of 665 patients with 683 eyes underwent emergency surgery for primary retinal detachment in the time span of 01.01.2018 - 31.12.2020. Median monthly number of surgeries was 20. During the first Swiss national lockdown (16.03.2020 - 19.04.2020), a minimum of 9 vitrectomies was recorded in March 2020. A maximum of 36 vitrectomies was conducted in August 2020. The mean age of patients was 61.5 years. Of the 665 patients, 133 (20.0%) were residents of the canton of Ticino. Median pre-operative BCVA was 0.25 over all three years, and no significant reduction in pre-operative BCVA was observed during or after the lockdown. The proportion of eyes with involvement of the macula was 52.2%. In 2018, this proportion (47.6%) was significantly lower than in 2019 and 2020 (Chi2 test, p < 0.001). However, cases with macular involvement in post lockdown months were not more frequent. Median time in days from reported symptom onset to hospitalisation was 5 days. In April 2020, the proportion of patients with > 14 days symptom duration was significantly higher (Chi2 test, p < 0.001). During the lockdown, there was a significant reduction in cases from Ticino. Also, patients from Ticino showed proportionally longer symptom duration after the lockdown. CONCLUSION: A significant reduction in the number of emergency vitrectomies was observed for the initial period of the coronavirus pandemic. Delayed emergency presentation is not assumed, since there was no increase in severity (i.e. macular involvement) or prolonged symptoms in the months following the lockdown. More protracted symptoms were only observed in patients from Ticino. The initial low numbers were generally made good later in the year.

Effect of Protective Measures on the Risk of SARS-CoV-2 Infection among Eye Clinic Staff Members.

BACKGROUND: Switzerland was strongly affected by the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that resulted in a nationwide lockdown in March 2020. Ophthalmologists were at most risk of contracting a SARS-CoV-2 infection due to their close working distance from patients. The aim of the study is to evaluate the overall effectiveness of protective measures on the risk of SARS-CoV-2 infection among employees in a large public eye hospital. MATERIAL AND METHODS: After lifting the lockdown in April 2020, standard precaution measures were taken, such as no handshaking and the use of operating face masks and a protective plastic shield on slit lamps and diagnostic devices. Only patients with no signs of SARS-CoV-2 disease were seen during the study period. Specific anti-SARS-CoV-2 IgG antibody titers were measured in eye clinic employees at the end of April 2020 (1st test phase) and in January 2021 (2nd test phase). The prevalence of SARS-CoV-2 IgG antibody titers among employees with daily patient contact was compared to staff members with no patient contact. RESULTS: The SARS-CoV-2 prevalence in employees with daily patient contact, with 0% in the 1st phase and 7.4% in the 2nd phase, was not significantly higher than the prevalence in the control group with no patient contact (0.9% in the 1st phase, p = 0.4; and 8.6% in the 2nd phase, p = 0.8). Furthermore, physicians were not at a significantly higher risk of SARS-CoV-2 infection compared to technicians, nurses, or office staff. CONCLUSIONS: This study shows that the abovementioned precaution measurements are effective in preventing transmission of SARS-CoV-2 infection in eye hospitals and enable us to resume practicing ophthalmology in a safe manner.

Outcomes and costs of Ranibizumab and Aflibercept treatment in a health-service research context.

BACKGROUND: To compare anti-VEGF treatments for macular disease in terms of costs and clinical outcomes. METHODS: We identified patients suffering from macular disease and treated either with aflibercept, ranibizumab or both at the largest public eye clinic in Switzerland between January 1st and December 31st 2016 who were insured in one of the two participating health insurance companies. Clinical data were extracted from the electronic health record system. The health insurers provided the health claim costs for the ophthalmologic care and the total health care costs of each patient in the observation period. Using multivariate regression models, we assessed the monthly ophthalmologic and the monthly total costs of patients with no history of switching (ranibizumab vs. aflibercept), patients with a history of switching from ranibizumab to aflibercept, patients switching during the observation period and a miscellaneous group. We examined baseline differences in age, proportion of males, visual acuity (letters), central retinal thickness (CRT) and treatment history before entering the study. We investigated treatment intensity and compared the changes in letters and CRT. RESULTS: The analysis involved 488 eyes (361 patients), 182 on ranibizumab treatment, and 63 on aflibercept treatment, 160 eyes with a history of switching from ranibizumab to aflibercept, and 45 switchers during follow-up and 38 eyes of the miscellaneous group. Compared to ranibizumab, monthly costs of ophthalmologic treatment were slightly higher for aflibercept treatment + 175.0 CHF (95%CI: 1.5 CHF to 348.3 CHF; p = 0.048) as were the total monthly costs + 581.0 CHF (95%CI: 159.5 CHF to 1002.4 CHF; p = 0.007). Compared to ranibizumab, the monthly treatment intensity with aflibercept was similar (+ 0.057 injections/month (95%CI -0.023 to 0.137; p = 0.162), corresponding to a projected annual number of 5.4 injections for ranibizumab vs. 6.1 injections for aflibercept. During follow-up, visus dropped by 0.7 letters with ranibizumab and increased by 0.6 letters with aflibercept (p = 0.243). CRT dropped by - 14.9 µm with ranibizumab and by - 19.5 µm with aflibercept (p = 0.708). The monthly costs of all other groups examined were higher. CONCLUSION: These real-life data show that aflibercept treatment is equally expensive, and clinical outcomes between the two drugs are similar.

Injections frequency and health care costs in patients treated with aflibercept compared to ranibizumab: new real-life evidence from Switzerland.

BACKGROUND: Previous analyses of real-life data indicated that injection frequency and health care costs did not differ for anti-VEGF treatment with aflibercept and ranibizumab. The objective of this study was to investigate whether this finding persisted when analysing a longer time period after licensing. METHODS: Retrospective analysis of health insurance claims data of two large Swiss basic health insurance plans including 28% of the Swiss population. Patients qualified for inclusion if aflibercept or ranibizumab treatment had been initiated between June 1, 2013 and November 1, 2014. Within this set, patients with at least 12 months of continuous insurance enrolment in the previous year, 12-month follow-up, and without change of anti-VEGF drug were considered. We examined the distribution of demographic data and patient characteristics between those receiving ranibizumab and those receiving aflibercept. Numbers of injections and associated health care expenditures observed during the 12-month follow-up period after incident treatment were the two outcomes considered. In multivariate regression analyses, controlling for possible confounding factors, we compared differences in these two outcomes between patients treated with aflibercept as compared to ranibizumab. RESULTS: A total of 3'058 patients were analysed, 790 (26%) receiving aflibercept and 2`268 receiving ranibizumab (74%). The use of aflibercept (average number of injections 6.2) as compared to ranibizumab (average number of injections 5.7) in the follow-up period of 1 to 12 months, was associated with a 12% increase in the injection frequency (95% confidence interval (CI) 6-17%; p < 0.001). CONCLUSIONS: Real-life data contradicts the assumption that aflibercept is used less frequently as compared to ranibizumab. This results in similar total health care expenditures for both anti-VEGF agents.

Colour Doppler analysis of ophthalmic vessels in the diagnosis of carotic artery and retinal vein occlusion, diabetic retinopathy and glaucoma: systematic review of test accuracy studies.

BACKGROUND: Colour Doppler analysis of ophthalmic vessels has been proposed as a promising tool in the diagnosis of various eye diseases, but the available diagnostic evidence has not yet been assessed systematically. We performed a comprehensive systematic review of the literature on the diagnostic properties of Colour Doppler imaging (CDI) assessing ophthalmic vessels and provide an inventory of the available evidence. METHODS: Eligible papers were searched electronically in (Pre) Medline, Embase and Scopus, and via cross-checking of reference lists. The minimum requirement to be included was the availability of original data and the possibility to construct a two-by-two table. Study selection, critical appraisal using the QUADAS II instrument and extraction of salient study characteristics was made in duplicate. Sensitivity and specificity was computed for each study. RESULTS: We included 11 studies (15 two-by-two tables) of moderate methodological quality enrolling 820 participants (range 30 to 118). In 44.4% participants were female (range 37-59% in specific subgroups). CDI was assessed for internal carotid stenosis, diabetic retinopathy, glaucoma, and branch or central retinal vein occlusion diagnosis. There was insufficient data to pool the results for specific illnesses. For the assessments of ophthalmic arteries, mean sensitivity was 0.69 (range 0.27-0.96) with a corresponding mean specificity of 0.83 (range 0.70-0.96). Mean sensitivity of the central retinal artery assessments was 0.58 (range 0.31-0.84) and the corresponding mean specificity was 0.82 (range 0.63-0.94). CONCLUSIONS: Robust assessments of the diagnostic value of colour Doppler analysis remain uncommon, limiting the possibilities to extrapolate its true potential for clinical practice. PROSPERO 2014:CRD42014014027.

Comparison of Eylea® with Lucentis® as first-line therapy in patients with treatment-naïve neovascular age-related macular degeneration in real-life clinical practice: retrospective case-series analysis.

BACKGROUND: To identify differences between Ranibizumab and Aflibercept in treatment-naïve patients with neovascular age-related macular degeneration (nvAMD) in a real-life clinical setting. METHODS: We compared two groups of patients with a fairly similar prognosis either receiving Aflibercept or Ranibizumab within a pro re nata regimen for 1 year. Changes in visual acuity (letters) and central foveal thickness (CFT) and frequency of injections after completing the loading phase were evaluated using two separate multivariate mixed linear models. RESULTS: When correcting for baseline differences between the Aflibercept (11 eyes) and Ranibizumab (16 eyes) group, there was neither divergence in visual acuity (-0.97 letters (95 % CI. -6.06-4.12); p = 0.709), nor a significant difference in the reduction of CFT (-25.16 µm, 95 % CI; (-78.01-27.68); p = 0.351) between the two groups 1 year after treatment initiation. Also, the number of injection did not differ (0.04 (95 % CI; -0.16-0.09); p = 0.565). CONCLUSION: In contrast to health claims, treatment-naïve nvAMD, Ranibizumab and Aflibercept were equivalent in terms of functional and morphologic outcomes and number of injections when studied in real-life clinical practice.

Penetration of a topically administered anti-tumor necrosis factor alpha antibody fragment into the anterior chamber of the human eye.

OBJECTIVE: To determine whether topically applied ESBA105, a single-chain antibody fragment against tumor necrosis factor (TNF)-α, could efficiently penetrate into the anterior chamber of the human eye. DESIGN: Multicenter, interventional cohort study. PARTICIPANTS: Otherwise healthy patients undergoing cataract surgery (cohorts I-III) or combined cataract surgery and vitrectomy (cohort IV). METHODS: ESBA105 (n = 57) or placebo (n = 22) was preoperatively applied as eye drops to 1 eye in patients scheduled for cataract surgery (n = 73) or combined cataract surgery and vitrectomy (n = 6). ESBA105 was administered on the day of surgery at 1-hour intervals (last dose 1 hour preoperatively) as 1.6 mg in 4 drops for cohort I (n = 15) and as 3.2 mg in 8 drops for cohorts II (n = 15) and IV (n = 6). Cohort III (n = 43) was randomized 1:1 in double-masked fashion to receive either ESBA105 6.4 mg or placebo over 4 days using 4 drops per day at 4-hour intervals (last dose 12 hours preoperatively). Aqueous humor (all cohorts), vitreous humor (cohort IV only), and blood samples (all cohorts) were collected for measurement of ESBA105. MAIN OUTCOME MEASURES: ESBA105 intraocular concentration. RESULTS: Both 4 times daily over 4 days dosing (cohort III) and 8 times daily dosing (cohorts II and IV) resulted in reliably high ESBA105 concentrations in aqueous humor. Mean molar excess of intraocular ESBA105 over its target (intraocular TNF-α) was calculated as 96-fold (cohort III) to 359-fold (cohorts II and IV). Results from the cohorts receiving 4 and 8 hourly drops per 1 day (cohorts I, II, and IV) indicated that dose-dependent intraocular concentrations of ESBA105 were achieved within hours of dosing. After 8 times daily dosing, 5 of 6 vitreous samples (cohort IV) had undetectable ESBA105 levels. ESBA105 was detected in 17 of 55 preoperative serum samples but no longer detectable in serum 1 day after surgery (0 of 19 samples). In cohort III, treatment-emergent adverse events were identical between ESBA105 and placebo groups (2 cases each of eye irritation). CONCLUSIONS: These results demonstrate that the topically applied single-chain antibody fragment ESBA105 penetrated into the anterior chamber of the human eye at therapeutic levels.

System usability, user satisfaction and long-term adherence to mobile hyperacuity home monitoring-prospective follow-up study.

PURPOSE: To evaluate the usability and long-term adherence to the mobile hyperacuity app Alleye in patients with retinal pathology. METHODS: We enroled 72 patients (95 eyes) mainly treated for wet AMD (48/95; 50.5%). We calculated changes of clinical characteristics and the System Usability Score (SUS), and personal ratings of usefulness and number of tests performed per month at a follow-up visit of eighteen months. RESULTS: At baseline, mean best corrected visual acuity (BCVA) was 74.9 letters (SD 14.8), mean age was 69.9 (SD 11.4) and 39/72 (54.2%) were female. Of included patients, 47/72 (65.2%) reported to use mobile devices daily. The retention rate until last follow-up was 73.6 % (53/72). The median SUS score at baseline was 90 (interquartile range (IQR) 82.5-95) and 92.5 (IQR 82.5-95) in the follow-up. No association between changes of SUS and clinical characteristics was seen. At baseline, 76.4% (55/72) stated that they would recommend the app to a friend, 83.3% (60/72) were very satisfied with the app and 58/72 (80.6%) of respondents said they trusted the app. These assessments remained similar among patients remaining on the program until the follow-up. Patients who dropped out of the study (n = 19) did not differ in age, gender, BCVA, and SUS at baseline, but stated that they did not use the mobile device daily (Odds Ratio 7.40 (95%CI: 2.32-23.65); p = 0.001). CONCLUSIONS: The majority of users willing to perform home monitoring with the Alleye app are satisfied with the usability and have a positive attitude towards its trustworthiness and usefulness.

Transforming ophthalmology in the digital century-new care models with added value for patients.

Ophthalmology faces many challenges in providing effective and meaningful eye care to an ever-increasing group of people. Even health systems that have so far been able to cope with the quantitative patient increase, due to their funding and the availability of highly qualified professionals, and improvements in practice routine efficiency, will be pushed to their limits. Further pressure on care will also be caused by new active substances for the largest group of patients with AMD, the so-called dry form. Treatment availability for this so far untreated group will increase the volume of patients 2-3 times. Without the adaptation of the care structures, this quantitative and qualitative expansion in therapy will inevitably lead to an undersupply.There is increasing scientific evidence that significant efficiency gains in the care of chronic diseases can be achieved through better networking of stakeholders in the healthcare system and greater patient involvement. Digitalization can make an important contribution here. Many technological solutions have been developed in recent years and the time is now ready to exploit this potential. The exceptional setting during the SARS-CoV-2 pandemic has shown many that new technology is available safely, quickly, and effectively. The emergency has catalyzed innovation processes and shown for post-pandemic time after that we are equipped to tackle the challenges in ophthalmic healthcare - ultimately for the benefit of patients and society.

Comparative Assessment of Retinal Blood Flow Velocity Changes Following Brimonidine and Brinzolamide Administration Using Retinal Function Imaging.

PURPOSE: Impaired ocular blood flow has been associated with the etiopathogenesis of glaucoma. Topical brimonidine lowers intraocular pressure, a major glaucoma risk factor. However, brimonidine's influence on retinal blood flow remains to be fully elucidated. Our aim was to compare the effect of topical brimonidine and brinzolamide administration on retinal blood flow velocity in second and third order vessels in healthy adults using the retinal function imager. METHODS: In 10 healthy probands between 23 and 32 years of age, one eye was randomly selected to receive 2 treatment rounds with 3 single doses of brimonidine 2 mg/mL and brinzolamide 10 mg/mL at 12-hour intervals each. The fellow eyes served as intra-individual controls. Immediately before the first drop and 2 hours after the last drop of each treatment round, all subjects were examined, including Goldmann tonometry, Pascal tonometry, assessment of retinal blood flow velocity using the retinal function imager, as well as blood pressure and pulse measurements. RESULTS: Intraocular pressure decreased significantly in treated eyes while remaining stable in control eyes, indicating reliable application of brimonidine and brinzolamide drops. In contrast, retinal blood flow velocities did not demonstrate any significant differences between groups after both treatment rounds. CONCLUSIONS: Neither brimonidine nor brinzolamide appear to alter retinal blood flow velocity in a clinically relevant manner. The slight velocity changes detected in our study are likely physiologic fluctuations. Our findings do not support the rationale of a detrimental effect of topical brimonidine on ocular blood flow and hence brimonidine may be further administered for lowering intraocular pressure with the appropriate caution. However, our study is strongly limited by the small sample size and, thus, further research with larger cohorts of healthy volunteers and patients with glaucoma is needed to confirm the results. TRANSLATIONAL RELEVANCE: The study provides information about the effect of the topically administered antiglaucoma medications brimonidine and brinzolamide on the ocular blood flow and its regulation. The findings indicate that beside the lowering of IOP there is no evidence for an additional effect on the development of glaucoma.

False alarms and the positive predictive value of smartphone-based hyperacuity home monitoring for the progression of macular disease: a prospective cohort study.

BACKGROUND: Home monitoring of hyperacuity allows early detection of progression in exudative neovascular age-related macular degeneration (nvAMD) and diabetic macular oedema (DMO). However, false alarms may pose a significant burden to both patients and healthcare professionals alike. PURPOSE: To assess the false alarm rate and positive predictive value of smartphone-based home monitoring of nvAMD and DMO. METHODS: Patients treated with anti-angiogenic therapy in a pro re nata scheme for nvAMD or DMO at the Medical Retina service (Lucerne, Switzerland) between March and June 2016 were included in this prospective cohort study. The home monitoring test Alleye (Oculocare Ltd, Switzerland) provided a session score from 0-100 in addition to a traffic-light system feedback via the smartphone application. Three consecutive "red" scores were considered as a positive test or alarm signal. Specificity, 1-specificity (false alarm rate) and the predictive value for optical coherence tomography-based disease progression were analysed. RESULTS: 73 eyes of 56 patients performed 2258 tests in 222 "follow-up periods". Progression was observed in 141 periods (63.5%). The specificity of the test was 93.8% (95% CI: 86.2-98.0%), the false alarm rate 6.1% (95% CI: 2.0-13.8%), and the positive predictive value 80.0% (95% CI: 59.3-93.2%) for the detection of progression. CONCLUSION: False alarm rates for the detection of progression in macular disease via home monitoring is low. These findings suggest that home monitoring may be a useful adjunct for remote management of nvAMD and DMO.

Visual outcomes and treatment adherence of patients with macular pathology using a mobile hyperacuity home-monitoring app: a matched-pair analysis.

OBJECTIVE: We compared patients with neovascular age-related macular degeneration (nvAMD), diabetic macular oedema (DMO) and other macular pathologies testing their vision with the hyperacuity home-monitoring app Alleye to patients not performing home-monitoring regarding clinical outcomes and clinical management. DESIGN: Matched-pair analysis. SETTING: Retina Referral Centre, Switzerland. PARTICIPANTS: For each eye using Alleye, we matched 2-4 controls not using home-monitoring based on age, gender, number of previous intravitreal injections (IVI), best corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study letters), central macular thickness (CRT) and time point of enrolment, using the Mahalanobis distance matching algorithm. We included 514 eyes (288 patients); 107 eyes with nvAMD using home monitoring and 218 controls not using home monitoring, 25 eyes with DMO (n=52 controls) and 40 eyes with miscellaneous conditions (n=72 controls). 173 eyes (33.7%) received no IVI during follow-up. MAIN OUTCOME MEASURES: Improvement of ≥5 letters, number of injection visits and treatment retention after correcting for differences in baseline characteristics with multivariate analyses. RESULTS: The mean follow-up duration was 809 days (range 147-1353) and the mean number of IVI/year among treated eyes was 6.7 (SD 3.1). Mean age at baseline was 70.4 years (SD 10.9), BCVA was 77.6 letters (SD 11.6) and CRT was 263.6 µm (SD 86.7) and was similar between patients using and not using home monitoring. In multivariate analyses, patients using home monitoring had a higher chance to improve visual acuity by ≥5 letters (OR 1.67 (95% CI 1.01 to 2.76; p=0.044)) than controls. Treated eyes using home monitoring had less injection visits/year (-0.99 (95% CI -1.59 to -0.40; p=0.001)) and a longer treatment retention +69.2 days (95% CI 2.4 to 136.0; p=0.042). These effects were similar across retinal pathologies. CONCLUSIONS: This data suggest that patients capable of performing mobile hyperacuity home monitoring benefit in terms of visual acuity and discontinue treatment less often than patients not using home monitoring.

Reliability and diagnostic performance of a novel mobile app for hyperacuity self-monitoring in patients with age-related macular degeneration.

PURPOSE: To assess the reliability and the diagnostic performance of a novel CE (European Conformity)-marked and FDA (Food and Drug Administration)-cleared dot patient self-monitoring test (Alleye, Oculocare medical Inc.) for the detection and characterization of metamorphopsia in age-related macular degeneration (AMD). METHODS: Three consecutive tests were performed in 63 wet AMD, 26 dry AMD, and 19 age-matched healthy eyes. In addition, the test was performed in 34 young healthy eyes. The mean Alleye score and standard deviations (SDs) were calculated for each eye and group. We compared and tested healthy with dry and wet AMD eyes and assessed the extent to which the test discriminated between healthy subjects and patients with dry and wet AMD using the area under the receiver operating characteristic curve (AUC). RESULTS: The mean (SD) Alleye score was 49.5 (16.1) in wet AMD eyes, 62.1 (22.5) in dry AMD eyes, 69.8 (10.2) in age-matched healthy eyes, and 85.3 (10.0) in young healthy subjects. Compared to age-matched healthy subjects, the AUC (95% confidence interval) to detect wet AMD was 0.845 (0.759-0.932), and 0.660 (0.520-0.799) to discriminate between dry and wet AMD. Compared to young healthy subjects, the AUC to detect dry AMD was 0.799 (0.675-0.923), and 0.969 (0.940-0.997) to detect wet AMD. CONCLUSIONS: This is the first assessment of Alleye in clinical practice. The test is highly accurate to detect wet AMD and reasonably accurate to classify dry vs. wet AMD. Data from longitudinal monitoring and its role in the therapeutic management of AMD is warranted.

Test performance of optical coherence tomography angiography in detecting retinal diseases: a systematic review and meta-analysis.

OBJECTIVE: To investigate the diagnostic accuracy of optical coherence tomography angiography (OCTA) in detecting vascular characteristics of chorio-retinal disease. METHODS: Evidence acquisition: We searched Web of Science, Scopus, and Medline by the citation of references and complemented these electronic searches by checking the list of references of included and review articles. Screening, selection, assessment, and extraction was performed in parallel by two authors. RESULTS: Evidence synthesis: Systematic review and exploratory meta-analysis. The ten studies that contributed to the meta-analysis enrolled 440 eyes and allowed constructing ten two-by-two tables. The tables reported on detection of choroidal neovascularization (CNV) in eyes suffering from either age-related macular degeneration (4), central serous chorioretinopathy (2), myopia (2), foveomacular vitelliform dystrophy (1), or a mixed cohort suffering from multiple retinal diseases (1). Of the ten studies, six used a cohort and four a case-control design. We found a pooled sensitivity of 0.90 (95% confidence intervals (CIs): 0.82-0.95) and a pooled specificity of 0.97 (95% CI: 0.89-0.99). Corresponding positive and negative likelihood ratios were 32.3 (95% CI: 7.4-141.6) and 0.10 (95% CI: 0.06-0.20), respectively. No pooling was possible for retinal vascular parameters of diabetic retinopathy, polypoidal choroidal vasculopathy, or detection of CNV activity. CONCLUSIONS: The results of highly biased and heterogeneous studies assessing the diagnostic performance of OCTA highlight the need for further analyses of methodologically sound and sufficiently sized clinical evaluations.

Effect of total anti-VEGF treatment exposure on patterns of choroidal neovascularisation assessed by optical coherence tomography angiography in age-related macular degeneration: a retrospective case series.

OBJECTIVE: To compare clinical characteristics of patients suffering from neovascular age-related macular degeneration (nAMD) with mature and immature choroidal neovascularisation (CNV) as assessed by optical coherence tomography angiography (OCTA). To explore the effect of total anti-vascular endothelial growth factor exposure on the occurrence of mature CNV when correcting for potential confounders. METHODS AND ANALYSIS: In this retrospective case series, we included 40 eyes of 36 patients with nAMD with CNV assessed by OCTA at the Manchester Eye Hospital between June 2016 and June 2017. A retinal specialist masked to patient information graded CNV depicted on OCTA scans. For statistical comparisons, we used t-tests, Fisher's exact tests and a mixed-effects logistic regression model. RESULTS: 18 patients (20 eyes) were treatment naïve, and the mean number of intravitreal injections (IVI) in the remaining eyes was 18.4 (range 2-71). The mean duration of nAMD was 19.3 months (range 0-87.4). 25 eyes (62.5%) exhibited mature CNV. Eyes with mature CNV did not differ from those with immature CNV regarding age (+2.8 years; p=0.288) or duration of disease (+9.4 months; p=0.061). However, they had a higher number of IVIs (+3.1; p=0.035). Among eyes with best corrected visual acuity over 25 letters, there was a strong association between the number of IVIs (0 vs 1-20: OR 68.01 [95% CI 1.30 to 3546.99; p=0.036], 0 vs >20 IVI: OR 380.01 [95% CI 2.60 to 55 464.89; p=0.019]) and maturity status when correcting for potential confounders. CONCLUSION: Maturity status of CNV as assessed by OCTA may indicate treatment exposure of CNV in nAMD.

Automated deep learning design for medical image classification by health-care professionals with no coding experience: a feasibility study.

BACKGROUND: Deep learning has the potential to transform health care; however, substantial expertise is required to train such models. We sought to evaluate the utility of automated deep learning software to develop medical image diagnostic classifiers by health-care professionals with no coding-and no deep learning-expertise. METHODS: We used five publicly available open-source datasets: retinal fundus images (MESSIDOR); optical coherence tomography (OCT) images (Guangzhou Medical University and Shiley Eye Institute, version 3); images of skin lesions (Human Against Machine [HAM] 10000), and both paediatric and adult chest x-ray (CXR) images (Guangzhou Medical University and Shiley Eye Institute, version 3 and the National Institute of Health [NIH] dataset, respectively) to separately feed into a neural architecture search framework, hosted through Google Cloud AutoML, that automatically developed a deep learning architecture to classify common diseases. Sensitivity (recall), specificity, and positive predictive value (precision) were used to evaluate the diagnostic properties of the models. The discriminative performance was assessed using the area under the precision recall curve (AUPRC). In the case of the deep learning model developed on a subset of the HAM10000 dataset, we did external validation using the Edinburgh Dermofit Library dataset. FINDINGS: Diagnostic properties and discriminative performance from internal validations were high in the binary classification tasks (sensitivity 73·3-97·0%; specificity 67-100%; AUPRC 0·87-1·00). In the multiple classification tasks, the diagnostic properties ranged from 38% to 100% for sensitivity and from 67% to 100% for specificity. The discriminative performance in terms of AUPRC ranged from 0·57 to 1·00 in the five automated deep learning models. In an external validation using the Edinburgh Dermofit Library dataset, the automated deep learning model showed an AUPRC of 0·47, with a sensitivity of 49% and a positive predictive value of 52%. INTERPRETATION: All models, except the automated deep learning model trained on the multilabel classification task of the NIH CXR14 dataset, showed comparable discriminative performance and diagnostic properties to state-of-the-art performing deep learning algorithms. The performance in the external validation study was low. The quality of the open-access datasets (including insufficient information about patient flow and demographics) and the absence of measurement for precision, such as confidence intervals, constituted the major limitations of this study. The availability of automated deep learning platforms provide an opportunity for the medical community to enhance their understanding in model development and evaluation. Although the derivation of classification models without requiring a deep understanding of the mathematical, statistical, and programming principles is attractive, comparable performance to expertly designed models is limited to more elementary classification tasks. Furthermore, care should be placed in adhering to ethical principles when using these automated models to avoid discrimination and causing harm. Future studies should compare several application programming interfaces on thoroughly curated datasets. FUNDING: National Institute for Health Research and Moorfields Eye Charity.

A comparison of deep learning performance against health-care professionals in detecting diseases from medical imaging: a systematic review and meta-analysis.

BACKGROUND: Deep learning offers considerable promise for medical diagnostics. We aimed to evaluate the diagnostic accuracy of deep learning algorithms versus health-care professionals in classifying diseases using medical imaging. METHODS: In this systematic review and meta-analysis, we searched Ovid-MEDLINE, Embase, Science Citation Index, and Conference Proceedings Citation Index for studies published from Jan 1, 2012, to June 6, 2019. Studies comparing the diagnostic performance of deep learning models and health-care professionals based on medical imaging, for any disease, were included. We excluded studies that used medical waveform data graphics material or investigated the accuracy of image segmentation rather than disease classification. We extracted binary diagnostic accuracy data and constructed contingency tables to derive the outcomes of interest: sensitivity and specificity. Studies undertaking an out-of-sample external validation were included in a meta-analysis, using a unified hierarchical model. This study is registered with PROSPERO, CRD42018091176. FINDINGS: Our search identified 31 587 studies, of which 82 (describing 147 patient cohorts) were included. 69 studies provided enough data to construct contingency tables, enabling calculation of test accuracy, with sensitivity ranging from 9·7% to 100·0% (mean 79·1%, SD 0·2) and specificity ranging from 38·9% to 100·0% (mean 88·3%, SD 0·1). An out-of-sample external validation was done in 25 studies, of which 14 made the comparison between deep learning models and health-care professionals in the same sample. Comparison of the performance between health-care professionals in these 14 studies, when restricting the analysis to the contingency table for each study reporting the highest accuracy, found a pooled sensitivity of 87·0% (95% CI 83·0-90·2) for deep learning models and 86·4% (79·9-91·0) for health-care professionals, and a pooled specificity of 92·5% (95% CI 85·1-96·4) for deep learning models and 90·5% (80·6-95·7) for health-care professionals. INTERPRETATION: Our review found the diagnostic performance of deep learning models to be equivalent to that of health-care professionals. However, a major finding of the review is that few studies presented externally validated results or compared the performance of deep learning models and health-care professionals using the same sample. Additionally, poor reporting is prevalent in deep learning studies, which limits reliable interpretation of the reported diagnostic accuracy. New reporting standards that address specific challenges of deep learning could improve future studies, enabling greater confidence in the results of future evaluations of this promising technology. FUNDING: None.