Letter Score Research Articles

Low frequency ranibizumab versus dexamethasone implant for macular oedema secondary to branch retinal vein occlusion

BackgroundThe aim was to make a real‐world comparison of the efficacy of ranibizumab, dexamethasone and grid laser treatments in macular oedema due to branch retinal vein occlusion (BRVO).MethodsForty‐four eyes of 44 consecutive patients with macular oedema secondary to BRVO were included. Treatment arms comprised standard care (StCARE, n = 15), intravitreal ranibizumab (RNB, n = 14) and dexamethasone implant (DEX, n = 15). No rescue laser was performed in DEX and RNB groups. Main outcome measures were mean change in visual acuity (VA) and the percentage of patients who gained 10 or more letters from baseline to six months and central retinal thickness (CRT).ResultsImprovements in mean logMAR VA (p = 0.642) and letter score from baseline to month 6 were not statistically significantly different in all three groups. Mean follow‐up was 13.9 ± 10.7 months in RNB, 11.9 ± 6.3 in DEX and 11.4 ± 6.6 in StCARE. Mean number of injections was 2.4 ± 1.4 (range: 1–6) in RNB and 1.9 ± 0.7 (range: 1–3) in DEX group over the follow‐up period. Mean letter gain was 13.5 in DEX (p = 0.067), 7.1 in RNB (p = 0.553) and 4.5 in StCARE (p = 0.362). Mean CRT at baseline was 512.8 μm in DEX, 505.1 μm in RNB and 345.5 μm in the StCARE group. At the last visit, RNB provided the maximum reduction in CRT. Mean CRT decrease was −146.5 μm (28.6 per cent) in DEX, −241.3 μm (47.8 per cent) in RNB and −45.6 μm (13.2 per cent) in StCARE (p = 0.030). A statistically significant intraocular pressure elevation occurred in the DEX group (p = 0.005).ConclusionBoth RNB and DEX provided a significant resolution in macular oedema. Low frequency injections limited the visual gain in ranibizumab therapy. Visual results could be better with higher frequency injections and early start of treatment. Dexamethasone implants may be preferable in terms of visual improvement under low frequency injection conditions. Close follow‐up is mandatory for detection of intraocular pressure elevations. Laser monotherapy is not a reasonable first‐line option in the era of injection therapies.

Examining Admission Factors Predicting Success in a Doctor of Nursing Practice Program.

Graduate nursing programs are challenged to select students who are likely to succeed and who add to nursing workforce diversity. For this retrospective study, researchers examined 5 years of admission and retention data from a 4-year Bachelor-to-Doctor of Nursing Practice (DNP) program (n=144) at a large public midwestern university. Using a multinomial logistic regression analysis, four factors were examined to determine which predicted student success, delayed success, or failure: last 60-credit grade point average (GPA), admission essay score, average recommendation letter score, and demographic data (i.e., race, age, gender). GPA, age, and race were found to be significant predictors of student outcomes in this program. Writing and recommendation scores and gender did not predict student outcomes. DNP admission committees should consider the weight given to the GPA in their admission formulas and be prepared to work with retention committees to support older and minority students. [J Nurs Educ. 2018;57(1):49-52.].

Validity Evidence for a Residency Admissions Standardized Assessment Letter for Pediatrics

ABSTRACTConstruct: This study aims to provide validity evidence for the standardized Assessment Letter for Pediatrics as a measure of competencies expected of a 1st-year pediatrics resident as part of a pediatric residency admissions process. Background: The Narrative Letter of Recommendation is a frequently used tool in the residency admissions process even though it has poor interrater reliability, lacks pertinent content, and does not correlate with residency performance. A newer tool, the Standardized Letter, has shown validity evidence for content and interrater reliability in other specialties. We sought to develop and provide validity evidence for the standardized Assessment Letter for Pediatrics. Approach: All 2012 and 2013 applicants invited to interview at the University of Geneva Pediatrics Residency Program provided 2 standardized Assessment Letters. Content for the letter was based on CanMEDS roles and ratings of 6 desired competencies and an overall assessment. Validity evidence was gathered for internal structure (Cronbach's alpha and generalizability), response process (interrater reliability with intraclass correlation), relations to other variables (Pearson's correlation coefficient), and consequences (logistic regression to predict admission). Results: One hundred fourteen faculty completed 142 standardized Assessment Letters for 71 applicants. Average overall assessment was 3.0 of 4 (SD = 0.59). Cronbach's alpha was 0.93. The G-coefficient was 0.59. The decision study projected that four Assessment Letters are needed to attain a G-coefficient of 0.73. Applicant variance (28.5%) indicated high applicant differentiation. The Assessment Letter intraclass coefficient was 0.51, 95% confidence interval (CI) [0.43, 0.59]. Assessment Letter scores were correlated with the structured interview (r = .28), 95% CI [0.05, 0.51]; global rating (r = .36), 95% CI [0.13, 0.58]; and admissions decision (r = .25), 95% CI [0.02, 0.46]. Assessment Letter scores did not predict the admissions decision (odds ratio = 1.67, p = .37) after controlling for the unique contribution of the structured interview and global rating scores. Conclusion: Validity evidence supports use of the Assessment Letter for Pediatrics; future studies should refine items to improve predictive validity and explore how to best integrate the Assessment Letter into the residency admissions process.

Effect of Adding Dexamethasone to Continued Ranibizumab Treatment in Patients With Persistent Diabetic Macular Edema

ImportanceSome eyes have persistent diabetic macular edema (DME) following anti–vascular endothelial growth factor (anti-VEGF) therapy for DME. Subsequently adding intravitreous corticosteroids to the treatment regimen might result in better outcomes than continued anti-VEGF therapy alone.ObjectiveTo compare continued intravitreous ranibizumab alone with ranibizumab plus intravitreous dexamethasone implant in eyes with persistent DME.Design, Setting, and ParticipantsPhase 2 multicenter randomized clinical trial conducted at 40 US sites in 129 eyes from 116 adults with diabetes between February 2014 and December 2016. Eyes had persistent DME, with visual acuity of 20/32 to 20/320 after at least 3 anti-VEGF injections before a run-in phase, which included an additional 3 monthly 0.3-mg ranibizumab injections. Data analysis was according to intent to treat.InterventionsFollowing the run-in phase, study eyes that had persistent DME and were otherwise eligible were randomly assigned to receive 700 μg of dexamethasone (combination group, 65 eyes) or sham treatment (ranibizumab group, 64 eyes) in addition to continued 0.3-mg ranibizumab in both treatment arms as often as every 4 weeks based on a structured re-treatment protocol.Main Outcomes and MeasuresThe primary outcome was change in mean visual acuity letter score at 24 weeks as measured by the electronic Early Treatment Diabetic Retinopathy Study (E-ETDRS). The principal secondary outcome was change in mean central subfield thickness as measured with the use of optical coherence tomography.ResultsOf the 116 randomized patients, median age was 65 years (interquartile range [IQR], 58-71 years); 50.9% were female and 60.3% were white. Mean (SD) improvement in visual acuity from randomization was 2.7 (9.8) letters in the combination group and 3.0 (7.1) letters in the ranibizumab group, with the adjusted treatment group difference (combination minus ranibizumab) of –0.5 letters (95% CI, −3.6 to 2.5; 2-sided P = .73). Mean (SD) change in central subfield thickness in the combination group was –110 (86) μm compared with –62 (97) μm for the ranibizumab group (adjusted difference, –52; 95% CI, −82 to −22; 2-sided P < .001). Nineteen eyes (29%) in the combination group experienced increased intraocular pressure or initiated treatment with antihypertensive eyedrops compared with 0 in the ranibizumab group (2-sided P < .001).Conclusions and RelevanceAlthough its use is more likely to reduce retinal thickness and increase intraocular pressure, the addition of intravitreous dexamethasone to continued ranibizumab therapy does not improve visual acuity at 24 weeks more than continued ranibizumab therapy alone among eyes with persistent DME following anti-VEGF therapy.Trial Registrationclinicaltrials.gov Identifier: NCT01945866

SCORE2 Report 5: Vision-Related Function in Patients With Macular Edema Secondary to Central Retinal or Hemiretinal Vein Occlusion

To describe baseline vision-related function, measured with the National Eye Institute Visual Function Questionnaire (NEI VFQ-25), in patients with macular edema secondary to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) in the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2); evaluate the baseline relationship between NEI VFQ-25 scores with visual acuity letter score (VALS) and central retinal thickness; and compare baseline NEI VFQ-25 scores in SCORE2 participants with those in normal-vision reference populations and patients in other retinal vein occlusion trials. Multicenter, noninferiority randomized controlled trial. SCORE2 was designed to assess whether intravitreal bevacizumab is noninferior to intravitreal aflibercept for treatment of decreased vision attributable to macular edema owing to CRVO or HRVO. SCORE2 enrolled 362 participants, including 305 with CRVO and 57 with HRVO. Analyses were of cross-sectional baseline data. The main outcome measures were baseline NEI VFQ-25 composite and subscale scores. SCORE2 participants' baseline NEI VFQ-25 composite and subscale scores are significantly lower compared with 3 normal-vision reference populations (P < .01; except for ocular pain score) and similar to patients in other retinal vein occlusion clinical trials. Baseline VALS in the better eye was correlated with baseline NEI VFQ-25 composite and subscale scores of general vision, near activities, role difficulties, dependency, and color vision, with correlations ranging from 0.19 to 0.26 (P < .05 for each score). CRVO and HRVO patients in SCORE2 had significantly worse baseline patient-reported vision-related function than normal vision populations, despite the disease being primarily unilateral with typically excellent vision in the fellow eye.

Suprachoroidal Triamcinolone Acetonide for Retinal Vein Occlusion: Results of the Tanzanite Study

To compare the safety and efficacy of treatment with suprachoroidal triamcinolone acetonide (CLS-TA) plus intravitreal aflibercept vs. treatment with aflibercept alone in patients with macular edema due to retinal vein occlusion (RVO). Randomized masked controlled clinical trial. Forty-six patients with RVO. Subjects were randomized 1:1 to suprachoroidal injection of CLS-TA plus intravitreal aflibercept (combination arm) or sham suprachoroidal injection plus aflibercept (aflibercept arm), followed by aflibercept as needed at months 1, 2, and 3 in each arm. The primary efficacy end point was the number of protocol-required aflibercept re-treatments through month 3. Secondary outcomes included mean improvement from baseline best-corrected visual acuity (BCVA), central subfield thickness (CST), and the percentage of participants with CST ≤310 μm at each time point. The number of re-treatments were reduced in the combination arm compared with that in the aflibercept arm (23 vs. 9; -61%; P= 0.013) and the percentage of participants requiring no re-treatments was increased (78% vs. 30%; P= 0.003). The mean improvement from baseline BCVA letter score in combination vs. that in the aflibercept arms was 16.1 vs. 11.4 (P= 0.20) at month 1, 20.4 vs. 11.9 (P= 0.04) at month 2, and 18.9 vs. 11.3 (P= 0.09) at month 3. The mean baseline CST in the combination arm (731.1 μm) decreased into the normal range at month 1 (284.7 μm) and remained there at months 2 and 3 (272.4 μm and 285.4 μm). The mean baseline CST (727.5 μm) in the aflibercept arm decreased to 322.8 μm at month 1 and increased at months 2 and 3 (383.4μm and 384.6 μm). Edema resolution (CST ≤ 310 μm) occurred in 87.0%, 87.0%, and 78.3% of participants in the combination arm at months 1, 2, and 3, respectively, vs. 56.5%, 47.8%, and 47.8% of participants in the aflibercept arm. In the combination arm, 1 participant had cataract progression and 4 (2 with preexistent glaucoma) had increased intraocular pressure that was controlled with topical medication. Combination intravitreal aflibercept and suprachoroidal CLS-TA is well tolerated and significantly reduces the need for additional intravitreal aflibercept injections over a 3-month period in patients with RVO. Preliminary evidence suggests that combination therapy may sustain edema resolution and improve visual outcomes.

High-Dose Decanted Triamcinolone for Treatment-Resistant Persistent Macular Edema.

To report the outcomes of decanted high-dose intravitreal triamcinolone acetonide (HD-IVTA) injection for treatment-resistant persistent macular edema (ME). Seventy-seven eyes of 70 consecutive patients who failed prior treatments for persistent ME received as-needed HD-IVTA injections. Best-corrected visual acuity and central macular thickness (CMT) were assessed at all follow-up visits. Thirty-three eyes (42.8%) had ME following pars plana vitrectomy. The mean ETDRS letter score from baseline improved by 6.3 letters ± 11.5 letters at 3 months (P < .001) and 4.8 letters ± 11.4 letters at 12 months (P = .016). The mean change in CMT from baseline was significant at all follow-up visits (P < .001). During 1-year follow-up, 49 eyes (63.6%) required only one HD-IVTA injection. The mean time for reinjection was 6 months ± 2.4 months (range: 1.6 months to 10.5 months) after the first injection of HD-IVTA. The incidence of elevated intraocular pressure was 40.2% (31 of 77 eyes). Of these, one eye required glaucoma surgery. Among 14 phakic eyes, 21.4% (three eyes) developed cataract formation requiring surgery. A single HD-IVTA injection can provide a long duration of effect on ME of up to 6 months. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:717-726.].

Comparison of 12-month therapeutic effect of conbercept and ranibizumab for diabetic macular edema: a real-life clinical practice study

BackgroundTo compare the efficacy of intravitreal conbercept and ranibizumab in the treatment of diabetic macular edema (DME) in a real-life clinical practice.MethodsThis was a retrospective study. Among 62 Chinese patients with DME, 32 patients (36 eyes) received intravitreal conbercept (IVC) injections and 30 patients (32 eyes) received intravitreal ranibizumab (IVR) injections, once a month for 3 months followed by as needed therapy. All participants had at least 12 months of follow-up. We compared the changes in best-corrected visual acuity (BCVA) letter score and central retinal thickness (CRT) between groups, as well as the number of intravitreal injections delivered. Safety was assessed with the incidence of adverse events (AEs).ResultsAt month 12, the mean BCVA letter score improved by 9.3 ± 5.2 with conbercept, and by 8.9 ± 4.4 with ranibizumab, the mean CRT reduction was 138.4 ± 97.7 μm and 145.2 ± 72.5 μm, respectively. There was no statistically significant difference of improvement in BCVA (P = 0.756) and decrease in CRT (P = 0.748) between the two groups. The number of intravitreal injections delivered was significantly higher (P = 0.027) in the IVR group (7.2 ± 1.0 per eye) than in the IVC group (6.6 ± 0.9 per eye). There were no severe ocular adverse reactions or systemic adverse events.ConclusionsBoth conbercept and ranibizumab are effective in the treatment of DME, achieving the similar clinical efficacy. In comparison to ranibizumab, conbercept shows a longer treatment interval and fewer intravitreal conbercept injections are needed.

Real-world visual acuity outcomes between ranibizumab and aflibercept in treatment of neovascular AMD in a large US data set

PurposeTo examine 12-month real-world visual acuity outcomes and treatment patterns in neovascular age-related macular degeneration (nAMD) eyes, including those with pigment epithelial detachment (PED), receiving ranibizumab or aflibercept.Patients and methodsElectronic medical records were used to identify ranibizumab or aflibercept-treated nAMD eyes with 12 months follow-up from first prescription. The primary objective was to compare mean change in visual acuity (VA) between index and month 12, in eyes treated with ranibizumab and aflibercept to assess the non-inferiority of ranibizumab vs aflibercept using a −5 letter non-inferiority margin. The number of injections and non-injection visits during follow-up were key secondary objectives.ResultsA total of 3350 ranibizumab and 4300 aflibercept treatment-naive eyes were included. At month 12, mean change from index in VA letter score was −0.30 for ranibizumab and −0.19 for aflibercept (P=0.81). The adjusted difference of mean change was −0.14 (−0.79 to 0.51) (P=0.67) (generalized estimating equations method) confirming the non-inferiority of ranibizumab. Eyes received a similar number of injections during follow-up. The mean (±SD) number of ranibizumab and aflibercept injections were 6.70 (±2.54) and 7.00 (±2.40), respectively (P<0.0001). In PED eyes, the mean (±SD) change between baseline to month 12 was 1.25 (±11.3) for ranibizumab and −0.39 (±13.3) for aflibercept (adjusted between-group difference 1.80 (−0.71 to 4.30; P=0.16)) achieved with a mean (±SD) 7.85 (±2.68) ranibizumab and 7.47 (±2.45) aflibercept injections, (P=0.11).ConclusionsRanibizumab and aflibercept treatment yielded comparable VA outcomes in nAMD eyes, including those with PED, with similar treatment patterns over 12 months in real-world clinical practice.

The relationship between salivary C-reactive protein and cognitive function in children aged 11–14 years: Does psychopathology have a moderating effect?

Elevated C-reactive protein (CRP), a non-specific biomarker of systemic bodily inflammation, has been associated with more pronounced cognitive impairments in adults with psychiatric disorders, particularly in the domains of memory and executive function. Whether this association is present in early life (i.e., the time at which the cognitive impairments that characterise these disorders become evident), and is specific to those with emerging psychiatric disorders, has yet to be investigated. To this end, we examined the association between salivary CRP and cognitive function in children aged 11–14years and explored the moderating effect of psychopathology. The study utilised data from an established longitudinal investigation of children recruited from the community (N=107) that had purposively over-sampled individuals experiencing psychopathology (determined using questionnaires). CRP was measured in saliva samples and participants completed assessments of cognition (memory and executive function) and psychopathology (internalising and externalising symptoms and psychotic-like experiences). Linear regression models indicated that higher salivary CRP was associated with poorer letter fluency (β=−0.24, p=0.006) and scores on the inhibition (β=−0.28, p=0.004) and inhibition/switching (β=−0.36, p<0.001) subtests of the colour-word interference test, but not with performance on any of the memory tasks (working, visual, and verbal memory tasks). Results were largely unchanged after adjustment for psychopathology and no significant interactions between CRP and psychopathology were observed on any cognitive measure. Our findings provide preliminary evidence that elevated salivary CRP is associated with poorer cognitive function in early life, but that this association is not moderated by concurrent psychopathology. These findings have implications for early intervention strategies that attempt to ameliorate cognitive deficits associated with emerging psychiatric disorders. Further research is needed to determine whether salivary CRP levels can be used as a valid marker of peripheral inflammation among healthy adolescents.

Measuring the Value of New Drugs: Validity and Reliability of 4 Value Assessment Frameworks in the Oncology Setting.

Several organizations have developed frameworks to systematically assess the value of new drugs. To evaluate the convergent validity and interrater reliability of 4 value frameworks to understand the extent to which these tools can facilitate value-based treatment decisions in oncology. Eight panelists used the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), Institute for Clinical and Economic Review (ICER), and National Comprehensive Cancer Network (NCCN) frameworks to conduct value assessments of 15 drugs for advanced lung and breast cancers and castration-refractory prostate cancer. Panelists received instructions and published clinical data required to complete the assessments, assigning each drug a numeric or letter score. Kendall's Coefficient of Concordance for Ranks (Kendall's W) was used to measure convergent validity by cancer type among the 4 frameworks. Intraclass correlation coefficients (ICCs) were used to measure interrater reliability for each framework across cancers. Panelists were surveyed on their experiences. Kendall's W across all 4 frameworks for breast, lung, and prostate cancer drugs was 0.560 (P= 0.010), 0.562 (P = 0.010), and 0.920 (P < 0.001), respectively. Pairwise, Kendall's W for breast cancer drugs was highest for ESMO-ICER and ICER-NCCN (W = 0.950, P = 0.019 for both pairs) and lowest for ASCO-NCCN (W = 0.300, P = 0.748). For lung cancer drugs, W was highest pairwise for ESMO-ICER (W = 0.974, P = 0.007) and lowest for ASCO-NCCN (W = 0.218, P = 0.839); for prostate cancer drugs, pairwise W was highest for ICER-NCCN (W = 1.000, P < 0.001) and lowest for ESMO-ICER and ESMO-NCCN (W = 0.900, P = 0.052 for both pairs). When ranking drugs on distinct framework subdomains, Kendall's W among breast cancer drugs was highest for certainty (ICER, NCCN: W = 0.908, P = 0.046) and lowest for clinical benefit (ASCO, ESMO, NCCN: W = 0.345, P = 0.436). Among lung cancer drugs, W was highest for toxicity (ASCO, ESMO, NCCN: W = 0. 944, P < 0.001) and lowest for certainty (ICER, NCCN: W = 0.230, P = 0.827); and among prostate cancer drugs, it was highest for quality of life (ASCO, ESMO: W = 0.986, P = 0.003) and lowest for toxicity (ASCO, ESMO, NCCN: W = 0.200, P = 0.711). ICC (95% CI) for ASCO, ESMO, ICER, and NCCN were 0.800 (0.660-0.913), 0.818 (0.686-0.921), 0.652 (0.466-0.834), and 0.153 (0.045-0.371), respectively. When scores were rescaled to 0-100, NCCN provided the narrowest band of scores. When asked about their experiences using the ASCO, ESMO, ICER, and NCCN frameworks, panelists generally agreed that the frameworks were logically organized and reasonably easy to use, with NCCN rated somewhat easier. Convergent validity among the ASCO, ESMO, ICER, and NCCN frameworks was fair to excellent, increasing with clinical benefit subdomain concordance and simplicity of drug trial data. Interrater reliability, highest for ASCO and ESMO, improved with clarity of instructions and specificity of score definitions. Continued use, analyses, and refinements of these frameworks will bring us closer to the ultimate goal of using value-based treatment decisions to improve patient care and outcomes. This work was funded by Eisai Inc. Copher and Knoth are employees of Eisai Inc. Bentley, Lee, Zambrano, and Broder are employees of Partnership for Health Analytic Research, a health services research company paid by Eisai Inc. to conduct this research. For this study, Cohen, Huynh, and Neville report fees from Partnership for Health Analytic Research. Outside of this study, Cohen receives grants and direct consulting fees from various companies that manufacture and market pharmaceuticals. Mei reports a grant from Eisai Inc. during this study. The other authors have no disclosures to report. Study concept and design were contributed by Bentley and Broder, with assistance from Elkin and Cohen. Bentley took the lead in data collection, along with Elkin, Huynh, Mukherjea, Neville, Mei, Popescu, Lee, and Zambrano. Data interpretation was performed by Bentley and Broder, along with Elkin, Cohen, Copher, and Knoth. The manuscript was written primarily by Bentley, along with Elkin and Broder, and revised by Bentley, Broder, Elkin, Cohen, Copher, and Knoth. Select components of this work's methods were presented at ISPOR 19th Annual European Congress held in Vienna, Austria, October 29-November 2, 2016, and Society for Medical Decision Making 38th Annual North American Meeting held in Vancouver, Canada, October 23-26, 2016.

Macular Sensitivity Measured With Microperimetry in Stargardt Disease in the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Study

New outcome measures for treatment trials for Stargardt disease type 1 (STGD1) and other macular diseases are needed. Microperimetry allows mapping of light sensitivity of the macula and provides topographic information on visual function beyond visual acuity. To measure and analyze retinal light sensitivity of the macula in STGD1 using fundus-controlled perimetry (microperimetry). This was a multicenter prospective cohort study. A total of 199 patients and 326 eyes with molecularly confirmed (ABCA4) STGD1 underwent testing with the Nidek MP-1 microperimeter as part of the multicenter, prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study. Sensitivity of 68 retinal loci was tested, and the mean sensitivity (MS) was determined; each point was categorized as "normal," "relative," or "deep" scotoma. Mean sensitivity and the number of points with normal sensitivity, relative, or deep scotomas. Mean (SD) patient age was 34.2 (14.7) years, mean (SD) best-corrected visual acuity of all eyes was 47.8 (16.9) Early Treatment Diabetic Retinopathy Study letter score (approximately 20/100 Snellen equivalent), and mean MS of all eyes of all 68 points was 11.0 (5.0) dB. The median number of normal points per eye was 49 (mean [SD], 41.3 [20.8]; range, 0-68); abnormal sensitivity and deep scotomas were more prevalent in the central macula. Mean sensitivity was lower in the fovea (mean [SD], 2.7 [4.4] dB) than in the inner (mean [SD], 6.8 [5.8] dB) and outer ring (mean [SD], 12.7 [5.3] dB). Overall MS per eye was 0.086 dB lower per year of additional age (95% CI, -0.13 to -0.041; P < .001) and 0.21 dB lower per additional year of duration of STGD1 (95% CI, -0.28 to -0.14; P < .001). Longer duration of STGD1 was associated with worse MS (β = -0.18; P < .001), with a lower number of normal test points (β = -0.71; P < .001), and with a higher number of deep scotoma points (β = -0.70; P < .001). We found 11 eyes with low MS (<6 dB) but very good best-corrected visual acuity of at least 72 Early Treatment Diabetic Retinopathy Study letter score (20/40 Snellen equivalent). We provide an extensive analysis of macular sensitivity parameters in STGD1 and demonstrate their association with demographic characteristics and vision. These data suggest microperimetry testing provides a more comprehensive assessment of retinal function and will be an important outcome measure in future clinical trials.

Validity and reliability of four value frameworks for cancer drugs.

6603 Background: Little is known about the validity and reliability of value assessment frameworks. Methods: Eight panelists used the ASCO, ESMO, ICER, and NCCN frameworks to conduct value assessments of 15 drugs for advanced lung and breast cancers and castration refractory prostate cancer. Panelists received instructions and published clinical data to complete the assessments, assigning each drug a numeric or letter score. We used Kendall’s W coefficient to measure convergent validity by cancer type among frameworks and intraclass correlation coefficients (ICC) to measure framework inter-rater reliability across cancers. Panelists were surveyed on their experiences. Results: Kendall’s W for breast, lung, and prostate cancer drugs were 0.560 ( p= 0.010), 0.562 ( p= 0.010), and 0.920 ( p&lt; 0.001), respectively. Pairwise and subdomain W are shown in the table. ICC (95% CI) for ASCO, ESMO, ICER, and NCCN were 0.800 (0.660-0.913), 0.818 (0.686-0.921), 0.652 (0.466-0.834), and 0.153 (0.045-0.371), respectively. Panelists generally agreed the frameworks were logically organized and easy to use. Conclusions: Convergent validity among the frameworks was fair to excellent, increasing with clinical benefit subdomain concordance and simplicity of drug trial data. Inter-rater reliability, highest for ASCO and ESMO, improved with clarity of instructions and specificity of score definitions. Continued use, analyses, and refinements of the frameworks will bring us closer to using value-based treatment decisions to improve patient care and outcomes. [Table: see text]

Effect of Bevacizumab vs Aflibercept on Visual Acuity Among Patients With Macular Edema Due to Central Retinal Vein Occlusion

ImportanceStudies have established the efficacy and safety of aflibercept for the treatment of macular edema due to central retinal vein occlusion. Bevacizumab is used off-label to treat this condition despite the absence of supporting data.ObjectiveTo investigate whether bevacizumab is noninferior to aflibercept for the treatment of macular edema secondary to central retinal or hemiretinal vein occlusion.Design, Setting, and ParticipantsThe SCORE2 randomized noninferiority clinical trial was conducted at 66 private practice or academic centers in the United States, and included 362 patients with macular edema due to central retinal or hemiretinal vein occlusion who were randomized 1:1 to receive aflibercept or bevacizumab. The first participant was randomized on September 17, 2014, and the last month 6 visit occurred on May 6, 2016. Analyses included data available as of December 30, 2016.InterventionsEyes were randomized to receive intravitreal injection of bevacizumab (1.25 mg; n = 182) or aflibercept (2.0 mg; n = 180) every 4 weeks through month 6.Main Outcomes and MeasuresThe primary outcome was mean change in visual acuity (VA) letter score (VALS) from the randomization visit to the 6-month follow-up visit, based on the best-corrected electronic Early Treatment Diabetic Retinopathy Study VALS (scores range from 0-100; higher scores indicate better VA). The noninferiority margin was 5 letters, and statistical testing for noninferiority was based on a 1-sided 97.5% confidence interval.ResultsAmong 362 randomized participants (mean [SD] age, 69 [12] years; 157 [43.4%] women; mean [SD] VALS at baseline, 50.3 [15.2] [approximate Snellen VA 20/100]), 348 (96.1%) completed the month 6 follow-up visit. At month 6, the mean VALS was 69.3 (a mean increase from baseline of 18.6) in the bevacizumab group and 69.3 (a mean increase from baseline of 18.9) in the aflibercept group (model-based estimate of between-group difference, −0.14; 97.5% CI, −3.07 to ∞; P = .001 for noninferiority), meeting criteria for noninferiority. Ocular adverse events in the aflibercept group included 4 participants with intraocular pressure (IOP) more than 10 mm Hg greater than baseline; ocular adverse events in the bevacizumab group included 1 participant with endophthalmitis (culture negative), 9 with IOP more than 10 mm Hg greater than baseline, 2 with IOP higher than 35 mm Hg, and 1 with angle-closure glaucoma not attributed to the study drug or procedure.Conclusions and RelevanceAmong patients with macular edema due to central retinal or hemiretinal vein occlusion, intravitreal bevacizumab was noninferior to aflibercept with respect to visual acuity after 6 months of treatment.

Baseline Factors Associated With 6-Month Visual Acuity and Retinal Thickness Outcomes in Patients With Macular Edema Secondary to Central Retinal Vein Occlusion or Hemiretinal Vein Occlusion

Macular edema (ME) is the leading cause of decreased visual acuity (VA) associated with retinal vein occlusion (RVO). Identifying factors associated with better outcomes in RVO eyes treated with anti-vascular endothelial growth factor (VEGF) therapy may provide information useful in counseling patients. To investigate baseline characteristics associated with 6-month VA and central subfield thickness (CST) outcomes in participants in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). A total of 362 patients with central RVO or hemi-RVO were enrolled between September 17, 2014, and November 18, 2015, and randomized 1:1 in a masked fashion to receive bevacizumab or aflibercept. At month 6, 348 participants (96%) had VA outcomes measured and 335 participants (93%) had spectral domain optical coherence tomography outcomes measured. The current data analysis was conducted from February 27, 2017, to April 7, 2017. Eyes were randomly assigned to receive an intravitreal injection of bevacizumab, 1.25 mg, or aflibercept, 2.0 mg, at baseline and every 4 weeks, with the primary outcome measured at 6 months. Change from baseline in VA letter score (VALS), VALS gain of 15 or more, change from baseline in CST, CST less than 300 µm, and resolution of ME. Baseline factors associated with 6-month outcome at the 0.05 level in univariate regressions were included in multivariate regressions, with those significant after multiplicity control by the Hochberg method reported. The mean (SD) age of patients was 69 (12) years, and 43% were women. Younger patient age (odds ratio [OR], 0.95 per year of age; 95% CI, 0.93-0.98; P = .007) and lower baseline VALS (OR, 0.96 per letter; 95% CI, 0.94-0.98; P < .001) were associated with a 6-month VALS gain of 15 or greater. Compared with bevacizumab, aflibercept treatment was associated with a higher odds of ME resolution (OR, 3.59; 95% CI, 2.22-5.80; P < .001) and CST less than 300 µm (OR, 5.30; 95% CI, 2.40-11.67; P = .001), but not with a better VA outcome. Macular edema was less likely to resolve in eyes that received anti-VEGF treatment prior to study participation (OR, 0.33; 95% CI, 0.17-0.64; P = .03). In eyes treated with bevacizumab or aflibercept, younger age and worse baseline VALS were associated with better 6-month VA outcomes. Aflibercept treatment was associated with more favorable spectral domain optical coherence tomography outcomes but not VA outcomes. These findings may be useful in assessing expected response at month 6 after monthly injection of anti-VEGF agents for treating ME due to CRVO and HRVO. clinicaltrials.gov Identifier: NCT01969708.

The Effects of Acute Stress on Memory, Attention and Cognition in Healthy Human Volunteers

The study was designed to investigate the effects of an acute naturalistic stressor, namely, examination of stress on memory, attention and cognition in healthy human volunteers. Fifty-three students participated in this study. All the volunteers were assessed for their neuropsychological states, which are memory, attention and cognition, during non-examination and examination period. The neuropsychological tests used in this study were- logical memory test, digit span test, letter cancellation test, trail making test and Stroop test. It was revealed that there was significant difference (p&lt;0.05) in the score of logical memory II, backward and total score of digit span, time taken to complete letter cancellation test and score in part C of Stroop test in the exam period. The present study thus demonstrated that acute naturalistic stress improves attention while impairs delayed memory retrieval and cognition.Bangladesh Pharmaceutical Journal 20(1): 14-19, 2017

Efficacy of intravitreal aflibercept injections for Japanese patients with polypoidal choroidal vasculopathy.

PurposeTo evaluate the efficacy of intravitreal aflibercept therapy in treatment-naïve Japanese patients with polypoidal choroidal vasculopathy (PCV) using Early Treatment Diabetic Retinopathy Study (ETDRS) letter scores.Subjects and methodsThis study was a prospective, nonrandomized, interventional exploratory clinical trial performed in an institutional setting. Patients with PCV were treated with intravitreal aflibercept 2 mg/0.05 mL every 2 months after 3 initial monthly doses, for 1 year. Visual acuity test using the ETDRS chart and indocyanine green angiography was performed at baseline and at 6 and 12 months after initiating the treatment, in addition to routine examinations performed at each visit. The main outcome measure was the proportion of patients who achieved <15 ETDRS letter score loss.ResultsTwenty-two patients were enrolled in this study. Nineteen (86%) patients were eligible for analysis. All the patients maintained their visual acuity (<15 ETDRS letter score loss) at 12 months. The ETDRS letter scores were 64.1 at baseline and 69.8 at 12 months (P<0.039). The polyps regressed completely in 14 (74%) patients at 12 months. Cataract progressed in 1 eye, but this progression was considered to be a senile change.ConclusionsJapanese patients with treatment-naïve PCV, who were treated with intravitreal aflibercept every 2 months after 3 initial monthly doses, exhibited a significant increase in ETDRS letter scores and a high rate of polyp resolution at 12 months.

The Clinical Importance of Changes in Diabetic Retinopathy Severity Score

To investigate the clinical importance of changes in diabetic retinopathy severity score (DRSS) in patients with diabetic macular edema (DME) treated with intravitreal ranibizumab. Post hoc analysis of the phase III RIDE and RISE studies of ranibizumab for treatment of DME. Four hundred sixty-eight eyes treated with ranibizumab from randomization with gradable DRSS on baseline fundus photographs. Visual and anatomic outcomes were examined in eyes grouped according to DRSS change from baseline to month24. Mean best-corrected visual acuity (BCVA) letter score change, proportion of patients with 15 or more Early Treatment Diabetic Retinopathy Study (ETDRS) letter score change, mean contrast sensitivity change, proportion of patients with resolved macular edema, and leakage on fluorescein angiography. Most (56.8%) patients treated with ranibizumab experienced 1-step or more improvement in DRSS from baseline to month 24; 40.0% had no change, and 3.2% experienced DRSS worsening. Patients with DRSS stability or improvement had greater mean BCVA letter score changes (+15.1,+14.2,+11.3, and+11.2 letters for ≥3-step improvement, ≥2-step improvement, 1-step improvement, and no DRSS change, respectively) compared with+5.0 letters in patients who had any DRSS worsening. Best-corrected visual acuity letter score gain of 15 letters or more was more common in patients with 2-step or 3-step or more DRSS improvement (51.9% and 44.6%, respectively) compared with those with a 1-step DRSS improvement, no change, or worsening (37.9%, 39.6%, and 26.7%, respectively). A loss of 15 letters or more in BCVA was more common in patients with any DRSS worsening (13.3%) compared with patients who had stable or improved DRSS (0%-2.8%). Resolution of macular edema was more common in patients with DRSS improvement: 84.2%, 87.7%, and 92.3% of patients with 1-step, 2-step or more, and 3-step or more improvement in DRSS achieved central foveal thickness of 250μm or less, compared with 65.2% and 53.3% of patients who had no DRSS change or any DRSS worsening. These findings provide further support that improvement in DRSS is a clinically important outcome that should be evaluated as a measure of treatment effectiveness in future studies of diabetic eye disease.

AGE-RELATED CLINICAL OUTCOME AFTER MACULAR HOLE SURGERY.

To evaluate functional and anatomical retinal recovery according to patient age using spectral domain optical coherence tomography in eyes with surgically closed macular holes. We retrospectively studied 83 eyes with anatomically closed idiopathic macular holes after surgery confirmed by spectral domain optical coherence tomography. Patients were divided into four subgroups based on age (Group 1: ≤ 60, Group 2: 61-65, Group 3: 66-70, Group 4: > 70). Best-corrected visual acuity and reconstruction of the external limiting membrane and ellipsoid zone after surgery were documented for 12 months. Mean patient age was 64.5 ± 9.8 years (range 44-81). Mean visual improvement in logMAR units (ETDRS letter score) at 12 months was worse in older age subgroups (Group 1: 0.4 ± 0.3 [20], Group 2: 0.4 ± 0.3 [20], Group 3: 0.2 ± 0.3 [10], Group 4: 0.1 ± 0.3 [5], P = 0.001). When age was more than 65 years, total number of eyes with restored retinal microstructure after surgery was lower (22 eyes, 53.7%; 32 eyes, 76.2%; P = 0.018) and time (months) to structural recovery was longer (10.2, 7.1, P < 0.001) than age under 65 years. Visual improvement corresponded to recovery of the outer retinal layers. In multivariate analysis, patients of older age (odds ratio, 0.91; 95% CI, 0.89-0.93) had less visual improvement at month 12. Poor visual outcomes and delayed microstructural recovery occurred in older subjects after anatomically closed macular hole surgery. Older age may be indicative of poor clinical outcome in repaired macular holes.

SCORE2 Report 2: Study Design and Baseline Characteristics

To describe the design and baseline characteristics of participants in the Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2) and to compare with cohorts from other retinal vein occlusion trials. Phase III prospective, multicenter, randomized clinical trial designed to assess whether intravitreal bevacizumab is noninferior to intravitreal aflibercept for treatment of decreased vision attributable to macular edema associated with central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO). Total of 362 participants: 307 with CRVO and 55 with HRVO. Demographic and study eye characteristics are summarized and compared between CRVO and HRVO study participants. Baseline ophthalmic characteristics, including visual acuity and retinal thickness, and medical history characteristics, including hypertension, diabetes mellitus, and coronary artery disease. The mean age of participants was 69 years, 76% of participants were white, and 90% were non-Hispanic. There was a racial disparity with respect to disease type, with 38% of HRVO patients being black compared with 11% of CRVO patients (P value adjusted for multiple testing= 0.0001). This is similar to findings from the previous SCORE Study. Comorbidities included hypertension (77%), diabetes mellitus (31%), and coronary artery disease (15%). At baseline, mean visual acuity letter score was 50 (20/100) (range, 19-73 [20/400 to 20/40]), mean optical coherence tomography (OCT)-measured central subfield thickness was 678 μm (range, 300-1203 μm), and mean number of months from diagnosis of macular edema to randomization was 6 (range, 0-104 months). One hundred twenty (33%) SCORE2 participants had been treated previously with anti-vascular endothelial growth factor (anti-VEGF) therapy, with these participants having baseline visual acuity letter score and OCT-measured central subfield thickness similar to those without prior anti-VEGF treatment, but longer mean duration of macular edema before randomization (18 months vs. 1 month for those without prior anti-VEGF treatment; P < 0.0001). The SCORE2 cohort is a heterogeneous population, including both CRVO and HRVO eyes and both treatment-naïve eyes and eyes treated previously with anti-VEGF, which will allow study results to have broad applicability to CRVO and HRVO patients receiving treatment for macular edema. Similarities of the baseline characteristics of the SCORE2 population to other CRVO trial cohorts will allow meaningful comparisons of outcome results across trials.