Accuracy of Artificial Intelligence in Estimating Best-Corrected Visual Acuity From Fundus Photographs in Eyes With Diabetic Macular Edema.

Importance: Best-corrected visual acuity (BCVA) is a measure used to manage diabetic macular edema (DME), sometimes suggesting development of DME or consideration of initiating, repeating, withholding, or resuming treatment with anti-vascular endothelial growth factor. Using artificial intelligence (AI) to estimate BCVA from fundus images could help clinicians manage DME by reducing the personnel needed for refraction, the time presently required for assessing BCVA, or even the number of office visits if imaged remotely. Objective: To evaluate the potential application of AI techniques for estimating BCVA from fundus photographs with and without ancillary information. Design, Setting, and Participants: Deidentified color fundus images taken after dilation were used post hoc to train AI systems to perform regression from image to BCVA and to evaluate resultant estimation errors. Participants were patients enrolled in the VISTA randomized clinical trial through 148 weeks wherein the study eye was treated with aflibercept or laser. The data from study participants included macular images, clinical information, and BCVA scores by trained examiners following protocol refraction and VA measurement on Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Main Outcomes: Primary outcome was regression evaluated by mean absolute error (MAE); the secondary outcome included percentage of predictions within 10 letters, computed over the entire cohort as well as over subsets categorized by baseline BCVA, determined from baseline through the 148-week visit. Results: Analysis included 7185 macular color fundus images of the study and fellow eyes from 459 participants. Overall, the mean (SD) age was 62.2 (9.8) years, and 250 (54.5%) were male. The baseline BCVA score for the study eyes ranged from 73 to 24 letters (approximate Snellen equivalent 20/40 to 20/320). Using ResNet50 architecture, the MAE for the testing set (n = 641 images) was 9.66 (95% CI, 9.05-10.28); 33% of the values (95% CI, 30%-37%) were within 0 to 5 letters and 28% (95% CI, 25%-32%) within 6 to 10 letters. For BCVA of 100 letters or less but more than 80 letters (20/10 to 20/25, n = 161) and 80 letters or less but more than 55 letters (20/32 to 20/80, n = 309), the MAE was 8.84 letters (95% CI, 7.88-9.81) and 7.91 letters (95% CI, 7.28-8.53), respectively. Conclusions and Relevance: This investigation suggests AI can estimate BCVA directly from fundus photographs in patients with DME, without refraction or subjective visual acuity measurements, often within 1 to 2 lines on an ETDRS chart, supporting this AI concept if additional improvements in estimates can be achieved.

Correlation between change in central subfield thickness and change in visual acuity in macular edema due to retinal vein occlusion: post hoc analysis of COPERNICUS, GALILEO, and VIBRANT.

PURPOSE: Assess correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with macular edema due to retinal vein occlusion (RVO) that received intravitreal aflibercept injections (IAI). METHODS: Post hoc analysis of COPERNICUS and GALILEO trials for CRVO and VIBRANT trial for BRVO with relationships determined using Pearson correlation coefficient. RESULTS: In COPERNICUS, correlations (r) between change in CST and change in BCVA from baseline at weeks 12, 24, 52, and 100 were -0.36 (95% CI: -0.52, -0.18; P < 0.001), -0.38 (95% CI: -0.53, -0.20; P < 0.001), -0.44 (95% CI: -0.58, -0.27; P < 0.001), and -0.41 (95% CI: -0.56, -0.23; P < 0.001), respectively. CST changes accounted for only 21% of the variance in BCVA changes; every 100-µm decrease in CST was associated with a 2.1-letter increase in BCVA (P = 0.003). Similar findings were noted for GALILEO (r, -0.45 to -0.23) and VIBRANT (r, -0.36 to -0.32) trials. CONCLUSION: In eyes treated with IAI for macular edema due to RVO, correlation between change in CST and change in BCVA was weak to moderate. While change in CST may be helpful in determining the need for anti-VEGF therapy, these findings do not support using changes in CST as a surrogate for changes in visual acuity outcomes.

Correlation of Change in Central Subfield Thickness and Change in Visual Acuity in Neovascular AMD: Post Hoc Analysis of VIEW 1 and 2.

PURPOSE: Determine correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor agents. DESIGN: A post hoc analysis of VIEW 1 and 2 randomized clinical trials. METHODS: This analysis included participants randomized to ranibizumab 0.5 mg every 4 weeks (Rq4), intravitreal aflibercept injection 2 mg every 4 weeks (2q4), and intravitreal aflibercept injection 2 mg every 8 weeks after 3 monthly doses (2q8) to week 52, followed by capped as-needed (at least every 12 weeks) dosing to week 96. Relationship between changes in CST and BCVA was determined using Pearson correlation coefficient. RESULTS: Of 1815 eyes, 595 were assigned to the Rq4, 613 to 2q4, and 607 to 2q8 arms. Correlations (95% confidence intervals [CI]) at weeks 12, 52, and 96 were -0.08 (95% CI, -0.17 to 0.00), -0.05 (95% CI, -0.14 to 0.04), and -0.15 (95% CI, -0.24 to -0.06) for Rq4; -0.13 (95% CI, -0.21 to -0.04), -0.06 (95% CI, -0.14 to 0.03) and -0.04 (95% CI, -0.13 to 0.05) for 2q4, and -0.04 (95% CI, -0.12 to 0.05), -0.01 (95% CI, -0.09 to 0.08), and -0.01 (95% CI, -0.10 to 0.09) for 2q8. Linear regression analysis adjusted for relevant baseline factors showed CST changes accounted for 11% of BCVA changes. Every 100 µm decrease in CST was associated with a 0.3 letter decrease (P = .25) at week 52 and a 0.14 letter decrease (P = .69) at week 96. CONCLUSIONS: Weak or no correlation was found between changes in CST and BCVA with either agent or regimen, suggesting changes in CST should not be used as a surrogate for visual acuity outcomes in neovascular age-related macular degeneration.

Correlation of Change in Macular Thickness With Change in Visual Acuity in Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials.

Purpose: To assess the correlation between the change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in eyes with diabetic macular edema (DME) treated with fixed-dosing intravitreal aflibercept injection (IAI). Methods: This post hoc analysis of the VISTA and VIVID randomized controlled clinical trials, in which 862 eyes with central-involved DME were randomly assigned to IAI 2 mg every 4 weeks (2q4; 290 eyes), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8; 286 eyes), or macular laser (286 eyes) and followed through 100 weeks. Correlations between the change in CST and change in BCVA from baseline to weeks 12, 52, and 100 were assessed using the Pearson correlation. Results: The respective correlations (r [95% CI]) at weeks 12, 52, and 100 were -0.39 (-0.49 to -0.29), -0.27 (-0.38 to -0.15), and -0.30 (-0.41 to -0.17) in the 2q4 arm and -0.28 (-0.39 to -0.17), -0.29 (-0.41 to -0.17), and -0.33 (-0.44 to -0.20) in the 2q8 arm. Linear regression analysis of the correlation at week 100, adjusted for relevant baseline factors, showed CST changes accounted for 17% of the variance in BCVA changes; every 100-µm decrease in CST was associated with a 1.2-letter increase in BCVA (P = .001). Conclusions: Correlations between the change in CST and change in BCVA after 2q4 or 2q8 fixed-dosing IAI for DME were modest. Although a change in CST might be important in determining the need for antivascular endothelial growth factor for DME at follow-up, it was not a good surrogate for VA outcomes.

Celecoxib plus aspirin versus naproxen and lansoprazole plus aspirin: a randomized, double-blind, endoscopic trial.

BACKGROUND & AIMS: Patients requiring low-dose aspirin along with nonsteroidal anti-inflammatory drugs are at increased risk for gastrointestinal injury. This study compared the incidence of gastroduodenal ulcers in patients treated with low-dose aspirin and a cyclooxygenase-2 selective nonsteroidal anti-inflammatory drug or a nonselective nonsteroidal anti-inflammatory drug plus the proton pump inhibitor lansoprazole. METHODS: Subjects 18 years or older with osteoarthritis, without gastroduodenal ulcer or erosive esophagitis at baseline endoscopy, and a cardiovascular indication for prophylaxis low-dose (81 or 325 mg) aspirin were prescribed open-label aspirin and blindly randomized to celecoxib 200 mg/day or naproxen 500 mg twice daily plus lansoprazole 30 mg once daily. Endoscopy was performed at 12 weeks or early termination. RESULTS: One thousand forty-five subjects were randomized and received at least 1 dose of study medication, and 854 (n = 426 celecoxib, n = 428 naproxen plus lansoprazole) subjects with both baseline and final visit endoscopies were evaluable for the primary efficacy analysis. Among these subjects, the rate of endoscopically confirmed gastroduodenal ulcers was not different in the celecoxib (9.9%) and naproxen plus lansoprazole (8.9%; treatment difference [95% confidence interval], 1.0% [-2.9% to 4.9%]) groups. CONCLUSIONS: In patients with osteoarthritis taking low-dose aspirin, the use of celecoxib or naproxen plus lansoprazole resulted in similar rates of gastroduodenal ulceration.

Pharmacokinetics and pharmacodynamics of lansoprazole in children 13 to 24 months old with gastroesophageal reflux disease.

OBJECTIVES: To evaluate the pharmacokinetics and pharmacodynamics of lansoprazole in children between 13 and 24 months of age with gastroesophageal reflux disease (GERD). METHODS: From the population of 66 children with symptomatic GERD, erosive esophagitis (> or = grade 2) or esophageal pH < 4 for > 4.2% of the 24-h period who participated in a phase I/II, open-label, multicenter (11 sites) US study, a subanalysis of 8 toddlers between 13 and 24 months of age was performed. All children were treated, based on body weight, with lansoprazole 15 mg once daily for 8 to 12 weeks. If a child were still symptomatic after 2 weeks of treatment, then the dose of lansoprazole could be increased to twice daily at the discretion of the investigator. Pharmacokinetic parameters were assessed at day 5. Twenty-four-hour median intragastric pH and the percentage of time intragastric pH > 3 or > 4 were assessed at baseline and at day 5 of treatment. Symptom response was assessed by investigator interview and daily diary. Safety was monitored by physical examinations including vital signs, adverse event assessments and laboratory evaluations. RESULTS: Pharmacokinetic analysis of 5 children found a mean time to reach maximum concentration of 1.4 h, maximal plasma concentrations of 894 ng/mL, area under the concentration time curve of 1906 ng * h/mL and a half-life of 0.66 h. Significant (P < or = 0.027) increases from baseline to day 5 were observed in mean 24-h intragastric pH (2.76-3.52) and the percentages of time pH were > 3 (29.46%-55.36%) and pH was > 4 (16.96%-40.77%). Six of the 8 children had improvement in their overall GERD symptom severity on the basis of investigator assessment, and a reduction was seen in the percentage of days with moderate, severe or very severe GERD symptoms compared with baseline. The dosage of lansoprazole was increased in 3 of the 8 children. Median fasting serum gastrin level increased from 65.0 pg/mL at baseline to 136.5 pg/mL at the final visit. Treatment-related events were mild constipation (1 subject) and mild diarrhea (1 subject). CONCLUSIONS: Although larger studies are needed to confirm these results, lansoprazole displays pharmacokinetic and pharmacodynamic parameters in children between 13 and 24 months of age that are similar to those results observed in older children as well as adults.

Presenting symptoms of nonerosive and erosive esophagitis in pediatric patients.

Children and adolescents with symptomatic gastroesophageal reflux disease (GERD) and erosive esophagitis (EE) of grade >/=2 (n=45) or nonerosive esophagitis (NEE) (n=45) were assessed to determine the relationship between presenting symptoms, esophagitis severity, and patient age. Overall, regurgitation/vomiting, abdominal pain, and cough were the most frequent symptoms. The prevalence and severity of anorexia/feed refusal was significantly greater in EE versus NEE children; this symptom was also significantly more prevalent in younger (1-5 years) children (both NEE and EE groups) compared to older children. Cough was significantly less severe in NEE adolescents than in younger children. Cough, anorexia/feed refusal, and regurgitation/vomiting were more severe and heartburn was less severe in EE children aged 1-5 years compared with older patients. In conclusion, GERD in children manifests differently than that in adults and symptoms vary with patient age. Symptoms were not predictive of presence or lack of mucosal damage.

Coadministration of lansoprazole and naproxen does not affect the pharmacokinetic profile of methotrexate in adult patients with rheumatoid arthritis.

Drugs prescribed for rheumatoid arthritis are often associated with gastrointestinal toxicity, and proton pump inhibitors may be coadministered for gastroprotection. In this open-label study, the effect of lansoprazole 30 mg qd and naproxen 500 mg bid on the pharmacokinetic profile of methotrexate was investigated. Twenty-seven adult rheumatoid arthritis patients on stable oral methotrexate doses (7.5-15 mg/week) for a minimum of 3 months were enrolled. Methotrexate pharmacokinetics were assessed on days -1 (methotrexate alone) and 7 (methotrexate with lansoprazole and naproxen). Pharmacokinetics of methotrexate and 7-hydroxymethotrexate were not altered by coadministration of methotrexate with lansoprazole and naproxen; point estimates and 90% confidence intervals for the peak plasma concentration and area under the plasma concentration-time curve of methotrexate and 7-hydroxymethotrexate were within the 0.80 to 1.25 boundaries. Therefore, coadministration of naproxen and lansoprazole for 7 days does not affect the pharmacokinetic profile of low doses of methotrexate.

Taste comparisons for lansoprazole strawberry-flavoured delayed-release orally disintegrating tablet and ranitidine peppermint-flavoured syrup in children.

OBJECTIVE: To compare the flavour and taste preferences of two acid-inhibitory therapies in children. SUBJECTS AND SETTING: 104 (52 male and 52 female) healthy children aged 6-11 years participated in this phase IV single-centre, taste-test study after parental consent was obtained. METHODS: Children were divided into two groups based upon age: group 1 included children aged 6-8 years and group 2 included children aged 9-11 years. Within each group an equal number of male and female subjects were recruited. Within each of the four strata defined by group and sex, an equal number of subjects were randomised to taste the strawberry-flavoured lansoprazole 15mg orally disintegrating tablet or the ranitidine 75mg/5mL peppermint-flavoured syrup samples in position 1. In group 1, the lansoprazole 15mg delayed-release orally disintegrating tablet was dispersed in 5mL of water, while in group 2, children gently rolled the tablet on the tongue until dissolution, before swallowing the particles. Children given the dose of lansoprazole dispersed in water (group 1) and the ranitidine dose (groups 1 and 2) were to taste it, swish it in their mouth for up to 10 seconds, and then swallow it. Children were given ambient temperature water and unsalted crackers to cleanse the palate during a 10-minute break between tastings. MAIN OUTCOME MEASURES: After each tasting, children rated their degree of liking on a five-point facial hedonic scale (5 = like very much, 1 = dislike very much). Product preference was recorded after the tasting of both samples. RESULTS: Among group 1 and group 2 participants, 86.5% (45/52) and 90.4% (47/52) of children, respectively, 'liked' ('like a little' or 'like very much') the strawberry-flavoured lansoprazole orally disintegrating tablet. The proportion of children who 'liked' the peppermint-flavoured ranitidine syrup was lower than the proportion who liked lansoprazole, and the proportions were similar between the groups: 13.5% (7/52) in group 1 and 9.6% (5/52) in group 2. Children in both groups preferred the strawberry-flavoured lansoprazole delayed-release orally disintegrating tablet: 92% (95% CI 81.1, 97.8; p < 0.001) of those in group 1 and 98% (95% CI 89.7, 100.0; p < 0.001) of those in group 2. CONCLUSION: After tasting both products, >92% of children aged from 6-11 years preferred the strawberry-flavoured lansoprazole delayed-release orally disintegrating tablet, either dissolved in a small amount of water or allowed to dissolve on the tongue, over the peppermint-flavoured ranitidine syrup.

Ulcer recurrence in high-risk patients receiving nonsteroidalanti-inflammatory drugs plus low-dose aspirin: results of a post HOC subanalysis.

BACKGROUND: Concomitant aspirin use is a risk factor for nonsteroidal anti-inflammatory drug (NSAID)-associated upper gastrointestinal toxicity. In high-risk individuals, such as those with a history of NSAID-related gastric ulcer bleeding, gastroprotective therapy with a proton pump inhibitor has been reported to reduce the risk of recurrent aspirin-associated gastroduodenal ulcer bleeding. OBJECTIVE: This analysis compared the efficacy of misoprostol, lansoprazole, and placebo in reducing the risk of gastric or duodenal ulcer recurrence in patients taking NSAIDs and low-dose aspirin. METHODS: This post hoc subanalysis was based on a previous multicenter, prospective, randomized, double-blind, placebo-controlled, 12-week study in patients who had a history of gastric ulcer, were Helicobacter pylori negative, required chronic NSAID therapy, and were free of gastric or duodenal ulcer on baseline endoscopy. The study treatments were misoprostol 200 microg QID or lansoprazole 15 or 30 mg OD. The subanalysis included data from patients in the intent-to-treat cohort who took aspirin at an amount

Comparison of the pharmacokinetics of lansoprazole 15- and 30-mg sachets for suspension versus intact capsules.

OBJECTIVE: The pharmacokinetic profiles of single doses of lansoprazole 15- and 30-mg sachets for suspension were compared with those of corresponding doses of lansoprazole oral capsules. METHODS: Healthy adult male and female subjects were randomized (1:1 ratio) into 2 Phase 1, open-label, single-dose, 2-sequence, 2-period complete crossover studies. In the first study, each subject received 1 lansoprazole 15-mg sachet mixed with water and 1 lansoprazole 15-mg oral capsule; in the second study, each subject received 1 lansoprazole 30-mg sachet mixed with water and 1 lansoprazole 30-mg oral capsule. Administration of the 2 formulations was separated by a washout period of > or =7 days. Blood samples were collected before and after each administration to assess the pharmacokinetic parameters of lansoprazole and bioequivalence between suspension and capsule. RESULTS: Thirty-six subjects (19 males, 17 females) with a mean (SD) age of 32.0 (9.6) years and mean (SD) body weight of 68.6 (10.5) kg received lansoprazole 15 mg. Thirty-six subjects (22 males, 14 females) with a mean (SD) age of 38.0 (8.3) years and mean (SD) body weight of 75.1 (9.7) kg received lansoprazole 30 mg. The pharmacokinetic parameters of the 15- and 30-mg lansoprazole sachets for suspension were similar to those of the corresponding doses of the oral capsules. The mean (SD) values for C(max) and AUC from time 0 to infinity (AUC(0-infinity) for the lansoprazole 15-mg sachet (591.9 [242.3] ng/mL and 1614 [2065] ng.h/mL, respectively) did not differ significantly from those for the lansoprazole 15-mg capsules (578.6 [275.2] ng/mL and 1620 [2290] ng.h/mL, respectively). These parameters also did not differ significantly between the lansoprazole 30-mg sachet and 30-mg capsule: mean (SD) C(max), 1103 (428.3) and 1077 (465.6) ng/mL, respectively; mean (SD) AUC(0-infinity), 2655 (1338) and 2669 (1311) ng.h/mL, respectively. The 90% Cls for C(max) and AUC(0-infinity) ratios were contained within the 0.80 to 1.25 equivalence range, supporting bioequivalence. CONCLUSIONS: These findings suggest that the 15- and 30-mg lansoprazole sachets for suspension are bioequivalent to the corresponding doses of oral capsules. The sachet for suspension may provide an alternative route of administration to patients who have difficulty swallowing solid oral formulations.