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At‐home visual acuity in children using a custom iPhone application compared with standardized in‐office visual acuity testing
Roberts, Tawna L. , Bothun, Erick D. , Zhu, Yufeng, Henderson, Robert J. , Boyle, Nicole M, Leske, David A. , Wernimont, Suzanne M., Marino, Carrie E, Manh, Vivian M. , Youngerman, Jillian M, Qayum, Jennifer N, Srinivasan, Gayathri , Titelbaum, Jenna R. , Crouch, Eric R. , Colburn, Jeffrey, Esposito, Christina , Zeto, V Lori, Connolly, Katie, Bhakta, Rita M, Lorenzana, Ingryd J., McDowell, Paula, Beaulieu, Wesley T, Kraker, Raymond T, Holmes, Jonathan M, Pineles, Stacy L., Weise, Katherine K., Cotter, Susan A, Group, Pediatric Eye Disease Investigator, Beaulieu, Wesley T , Kraker, Raymond T , Hatt, Sarah R. , Raghuram, Aparna , McDowell, Paula S., Kraker, Raymond T. , Holmes, Jonathan M. , Cotter, Susan A.

Optometry and Vision Science | May 1, 2026 | Volume: 103 | Issue: 4 | Pages: No page available

10.1002/ovs2.70040 | PMID 42062237 Get It

ABSTRACT Purpose To validate a custom smartphone application for at‐home visual acuity (VA) measurement in children. Methods A total of 452 children aged 3–17.5 years participated. Certified examiners measured in‐office test–retest VA (logMAR) using gold‐standard Amblyopia Treatment Study HOTV (3‐to‐6‐year‐olds, younger cohort) or electronic Early Treatment of Diabetic Retinopathy Study (7‐to‐17.5‐year‐olds, older cohort) protocols at 3–4.5 m and app‐based VA at 1.5 m. Caregivers measured at‐home app‐based VA at 1.5 m. Results Comparing at‐home app‐based with gold‐standard VA, in eyes 20/40 or better, 95% (143/151) and 93% (91/98) of the younger and older cohorts were within 2 lines, respectively (mean differences: younger = −0.03, older = −0.04; 95% limits‐of‐agreement half‐width (LOA): younger = ±0.26, older = ±0.22). In eyes 20/50 or worse, 66% (42/64) and 75% (76/101) of the younger and older cohorts were within 2 lines, respectively (mean differences: younger = 0.11, older = 0.13, LOA: younger = ±0.50, older = ±0.51). Comparing in‐office app‐based VA with gold‐standard VA, in eyes 20/40 or better, 98% (160/164) and 94% (99/105) of the younger and older cohorts were within 2 lines, respectively (mean differences: younger = −0.03, older = −0.03; LOA: younger = ±0.22; older = ±0.24). In eyes 20/50 or worse, 85% (60/71) and 91% (101/111) of the younger and older cohorts were within 2 lines, respectively (mean differences: younger = 0.04; older = 0.04; LOA: younger = ±0.39; older = ±0.24). For gold‐standard test–retest, in eyes 20/40 or better, 99% (163/164) and 99% (104/105) of the younger and older cohorts had retest within 2 lines, respectively (mean differences: younger = 0.00; older = 0.01; LOA: younger = ±0.17; older = ±0.11). For 20/50 or worse, 92% (66/72) and 100% (111/111) in the younger and older cohorts were within 2 lines, respectively (mean differences: younger = 0.01; older = 0.02; LOA: younger = ±0.35; older = ±0.15). Conclusions Our app demonstrated good concordance with the gold standard at home and in the office for eyes with VA of 20/40 or better. However, concordance decreased considerably for eyes with VA 20/50 or worse, particularly at home.
Three-Year Outcomes Following TAVR in Younger (
Modine, Thomas , Tchétché, Didier , Mieghem, Nicolas M. Van , Deeb, G. Michael , Chetcuti, Stanley, Yakubov, Steven J. , Sorajja, Paul , Gada, Hemal, Mumtaz, Mubashir , Ramlawi, Basel , Bajwa, Tanvir , Crouch, John , Teirstein, Paul S., Kleiman, Neal S. , Iskander, Ayman, Chu, Michael , Sudre, Arnaud , Huang, Jian, Popma, Jeffrey J. , Forrest, John K. , Van Mieghem, Nicolas M , Bagur, Rodrigo , Chu, Michael W A , Berthoumieu, Pierre , Sudre, Arnaud , Adrichem, Rik , Ito, Saki , Forrest, John K , Modine, Thomas , Sorajja, Paul , Bagur, Rodrigo , Ito, Saki , Huang, Jian Qun , Reardon, Michael J.

Circulation: Cardiovascular Interventions | October 18, 2024 | Volume: 17 | Issue: 11 | Pages: No page available

10.1161/circinterventions.124.014018 | PMID 39421943 Get It

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an alternative to surgery in patients with severe aortic stenosis, but data are limited on younger, low-risk patients. This analysis compares outcomes in low-surgical-risk patients aged <75 years receiving TAVR versus surgery. METHODS: The Evolut Low Risk Trial randomized 1414 low-risk patients to treatment with a supra-annular, self-expanding TAVR or surgery. We compared rates of all-cause mortality or disabling stroke, associated clinical outcomes, and bioprosthetic valve performance at 3 years between TAVR and surgery patients aged <75 years. RESULTS: In patients <75 years, 352 were randomized to TAVR and 351 to surgery. Mean age was 69.1±4.0 years (minimum 51 and maximum 74); Society of Thoracic Surgeons Predicted Risk of Mortality was 1.7±0.6%. At 3 years, all-cause mortality or disabling stroke for TAVR was 5.7% and 8.0% for surgery ( P =0.241). Although there was no difference between TAVR and surgery in all-cause mortality, the incidence of disabling stroke was lower with TAVR (0.6%) than surgery (2.9%; P =0.019), while surgery was associated with a lower incidence of pacemaker implantation (7.1%) compared with TAVR (21.0%; P <0.001). Valve reintervention rates (TAVR 1.5%, surgery 1.5%, P =0.962) were low in both groups. Valve performance was significantly better with TAVR than surgery with lower mean aortic gradients ( P <0.001) and lower rates of severe prosthesis-patient mismatch ( P <0.001). Rates of valve thrombosis and endocarditis were similar between groups. There were no significant differences in rates of residual ≥moderate paravalvular regurgitation. CONCLUSIONS: Low-risk patients <75 years treated with supra-annular, self-expanding TAVR had comparable 3-year all-cause mortality and lower disabling stroke compared with patients treated with surgery. There was significantly better valve performance in patients treated with TAVR. REGISTRATION: URL: https://clinicaltrials.gov ; Unique identifier: NCT02701283.
Endocrine-Sensitive Disease Rate in Postmenopausal Patients With Estrogen Receptor–Rich/ERBB2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, or Their Combination
Cynthia, X. , Sanati, Souzan , Leitch, A. Marilyn , Unzeitig, Gary, Fernández-Martínez, Aranzazu , Fan, Cheng , Gibbs, Richard A. , Dockter, Travis , Hahn, Olwen, Guenther, Joseph M., Caudle, Abigail S. , Crouch, Erika C., Tiersten, Amy , Mita, Monica , Razaq, Wajeeha, Rimawi, Mothaffar F. , Weiss, Anna , Perou, Charles M. , Carey, Lisa A. , Dockter, Travis J, Carey, Lisa A , Perou, Charles M , Rimawi, Mothaffar , Fernandez-Martinez, Aranzazu , Suman, Vera J. , Vij, Kiran R , Anurag, Meenakshi , Hoog, Jeremy , Watson, Mark A. , Hieken, Tina J. , Wang, Yang , Winer, Eric P. , Hunt, Kelly K. , Ellis, Matthew J. , Partridge, Ann H.

JAMA Oncology | January 18, 2024 | Volume: 10 | Issue: 3 | Pages: 362

10.1001/jamaoncol.2023.6038 | PMID 38236590 Get It

Importance Adding fulvestrant to anastrozole (A+F) improved survival in postmenopausal women with advanced estrogen receptor (ER)–positive/ERBB2 (formerly HER2)–negative breast cancer. However, the combination has not been tested in early-stage disease. Objective To determine whether neoadjuvant fulvestrant or A+F increases the rate of pathologic complete response or ypT1-2N0/N1mic/Ki67 2.7% or less residual disease (referred to as endocrine-sensitive disease) over anastrozole alone. Design, Setting, and Participants A phase 3 randomized clinical trial assessing differences in clinical and correlative outcomes between each of the fulvestrant-containing arms and the anastrozole arm. Postmenopausal women with clinical stage II to III, ER-rich (Allred score 6-8 or &amp;gt;66%)/ERBB2-negative breast cancer were included. All analyses were based on data frozen on March 2, 2023. Interventions Patients received anastrozole, fulvestrant, or a combination for 6 months preoperatively. Tumor Ki67 was assessed at week 4 and optionally at week 12, and if greater than 10% at either time point, the patient switched to neoadjuvant chemotherapy or immediate surgery. Main Outcomes and Measures The primary outcome was the endocrine-sensitive disease rate (ESDR). A secondary outcome was the percentage change in Ki67 after 4 weeks of neoadjuvant endocrine therapy (NET) (week 4 Ki67 suppression). Results Between February 2014 and November 2018, 1362 female patients (mean [SD] age, 65.0 [8.2] years) were enrolled. Among the 1298 evaluable patients, ESDRs were 18.7% (95% CI, 15.1%-22.7%), 22.8% (95% CI, 18.9%-27.1%), and 20.5% (95% CI, 16.8%-24.6%) with anastrozole, fulvestrant, and A+F, respectively. Compared to anastrozole, neither fulvestrant-containing regimen significantly improved ESDR or week 4 Ki67 suppression. The rate of week 4 or week 12 Ki67 greater than 10% was 25.1%, 24.2%, and 15.7% with anastrozole, fulvestrant, and A+F, respectively. Pathologic complete response/residual cancer burden class I occurred in 8 of 167 patients and 17 of 167 patients, respectively (15.0%; 95% CI, 9.9%-21.3%), after switching to neoadjuvant chemotherapy due to week 4 or week 12 Ki67 greater than 10%. PAM50 subtyping derived from RNA sequencing of baseline biopsies available for 753 patients (58%) identified 394 luminal A, 304 luminal B, and 55 nonluminal tumors. A+F led to a greater week 4 Ki67 suppression than anastrozole alone in luminal B tumors (median [IQR], −90.4% [−95.2 to −81.9%] vs −76.7% [−89.0 to −55.6%]; P &amp;lt; .001), but not luminal A tumors. Thirty-six nonluminal tumors (65.5%) had a week 4 or week 12 Ki67 greater than 10%. Conclusions and Relevance In this randomized clinical trial, neither fulvestrant nor A+F significantly improved the 6-month ESDR over anastrozole in ER-rich/ERBB2-negative breast cancer. Aromatase inhibition remains the standard-of-care NET. Differential NET response by PAM50 subtype in exploratory analyses warrants further investigation. Trial Registration ClinicalTrials.gov Identifier: NCT01953588
Complications Occurring Through 5 Years Following Primary Intraocular Lens Implantation for Pediatric Cataract
Yen, Kimberly G., Repka, Michael X. , Sutherland, Desirae R. , Haider, Kathryn M. , Kraker, Raymond T. , Galvin, Jennifer, Li, Zhuokai , Holmes, Jonathan M. , Group, Pediatric Eye Disease Investigator, Wallace, David K. , Enyedi, Laura B. , Jones, Sarah K., Hug, Denise, Stahl, Erin D., Dent, Rebecca J., Kong, Lingkun , Wang, Serena , Gallerson, Bryan K., Hutchinson, Amy K., Lenhart, Phoebe D. , Brower, Judy, Morrison, David G., Ruark, Scott T., Mets-Halgrimson, Rebecca, Yoon, Hawke , Hamidullah, Aaliyah, Anderson, Jill S., Holleschau, Ann M., Superstein, Rosanne , Bélanger, Caroline, Fallaha, Nicole, Hamel, Patrick , Thibeault, Maryse, Tamkins, Susanna M. , Park, Hee-Jung S., Trumler, Anya A., Liu, Xiaonong, Astle, William F., Sanders, Emi , McOwen, Diana C., Gray, Michael E. , Yang, Michael B. , Bowman, Corey S., Therriault, Margaret, Smith, Heather , Whitaker, Michele E., Örge, Faruk , Grigorian, A. Paula, Baird, Alicia M., Strominger, Mitchell B. , Klein, Shelley, Kemmer, Jacquelyn D., Neiman, Alexandra E., Mendoza, Myra N., Frohwein, Jill J., Bremer, Don L., Cassady, Cybil, Golden, Richard P., Jordan, Catherine O., Oravec, Sara A., Yanovitch, Tammy L. , Lunsford, Keven, Nye, Christina, Shea, Caroline, Stillman, SueAnn M., Iderstine, Stephen C. Van, Robertson, Elisa, Cruz, Oscar A., Ghadban, Rafif, Govreau, Dawn, Longmuir, Susannah Q. , Shan, Xiaoyan, Taylor, Kate , Powell, Christine, Hammond, Benjamin P., Gearinger, Matthew D., Czubinski, Andrea, Salvin, Jonathan, Fisher, Alicia, Lee, Katherine A., Brooks, Daniel , Schweinler, Bonita R., Sala, Nicholas A., Sala, Allyson M., Summers, Allison I. , Karr, Daniel J. , Wilson, Lorri B., Rauch, Paula K., O’Hara, Mary, Gandhi, Nandini, Hashmi, Tania, Colburn, Jeffrey, Dittman, Eileen, Whitfill, Charles R., Wheeler, Amy M., McCourt, Emily A. , Singh, Jasleen , Welnick, Nanastasia, Azar, Nathalie F., Baker, Joseph, Droste, Patrick J. , Peters, Robert J., Hilbrands, Jan, Pineles, Stacy L., Bernardo, Marianne J., Peterson, Edward, Peterson, Charla H., Kumar, Kartik , Melese, Ephrem, Lingua, Robert W., Grijalva, Jeff, Crouch, Earl R., Crouch, Earl R., Ventura, Gaylord, Anninger, William, Benson, Shawn L., Karp, Karen A. , Smith, Jordana M., Brickman-Kelleher, Jill, Ticho, Benjamin H., Khammar, Alexander J., Clausius, Deborah A., Guo, Suquin, Chamberlain, Carolyn, Schloff, Susan, Madigan, William P., Burkman, Donna, Ramsey, Jean E., McConnell, Kate H. , Friedman, Ilana, Rosado, José , Sauberan, Donald P., Hemberger, Jody C., Davis, Patricia L., Rudaitis, Indre, Lowery, Robert S., Cupit, Shawn, Bothun, Erick D. , Wernimont, Suzanne M., Neilsen, Rebecca A., Baran, Francine, Gladstone, Amy, Smith, Justin , Mellott, Mei, Kieser, Troy, Erzurum, S. Ayse , Colon, Beth, Shah, Birva, Quebbemann, Micaela, Austin, Darrell S., Boyle, Nicole M., Conner, Courtney L., Chandler, Danielle L. , Donahue, Quayleen, Fimbel, Brooke P., Robinson, Julianne L., Hercinovic, Amra, Hoepner, James E., Kaplon, Joseph D., Melia, Michele , Ortiz, Gillaine, Woodard, Victoria C., Stutz, Kathleen M., Everett, Donald F., Diener‐West, Marie , Baker, John D., Davis, Barry R. , Phelps, Dale L. , Poff, Stephen W., Tychsen, Lawrence , Bradfield, Yasmin S., Foster, Nicole C. , Plager, David A. , Silver, Jayne L., Weise, Katherine K., Verderber, Lisa C. , Dean, Trevano W., Campomanes, Alejandra G. de Alba , Young, Marielle P. , Rahmani, Bahram , Whitehead, George F., Lambert, Scott R. , Kurup, Sudhi P. , Kraus, Courtney L. , Hatt, Sarah R. , Cotter, Susan A. , Group, Pediatric Eye Disease Investigator, Freedman, Sharon F. , Prakalapakorn, Sasapin Grace , Ranaivo, Hantamalala Ralay , Areaux, Raymond G. , Chang, Ta Chen , Traboulsi, Elias I. , Ghasia, Fatema F. , Chen, Vicki, Rogers, David L. , LaRoche, G. Robert, Larson, Scott A. , Clarke, Michael W. , Hendricks, Dorothy H. , Jin, Jing , Brooks, Daniel, Rauch, Paula K., Baker, Joseph, Peterson, Edward, Crouch, Earl R., Suh, Donny Won , Christiansen, Stephen P. , Herlihy, Erin P. , Beck, Roy W. , Henderson, Robert J. , Wu, Rui , Saunders, Richard Anthony , Salchow, Daniel J. , Birch, Eileen E. , Manny, Ruth E. , Holmes, Jonathan M.

JAMA Ophthalmology | June 23, 2023 | Volume: 141 | Issue: 8 | Pages: 705

10.1001/jamaophthalmol.2023.2335 | PMID 37347490 Get It

Importance Lensectomy with primary intraocular lens (IOL) implantation is often used in the management of nontraumatic pediatric cataract, but long-term data evaluating the association of age and IOL location with the incidence of complications are limited. Objective To describe the incidence of complications and additional eye surgeries through 5 years following pediatric lensectomy with primary IOL implantation and association with age at surgery and IOL location. Design, Setting, and Participants This prospective cohort study used Pediatric Eye Disease Investigator Group cataract registry data from 61 institution- and community-based practices over 3 years (June 2012 to July 2015). Participants were children younger than 13 years without baseline glaucoma who had primary IOL implantation (345 bilateral and 264 unilateral) for nontraumatic cataract. Data analysis was performed between September 2021 and January 2023. Exposures Lensectomy with primary IOL implantation. Main Outcome and Measures Five-year cumulative incidence of complications by age at surgery (&amp;lt;2 years, 2 to &amp;lt;4 years, 4 to &amp;lt;7 years, and 7 to &amp;lt;13 years) and by IOL location (sulcus vs capsular bag) were estimated using Cox proportional hazards models. Results The cohort included 609 eyes from 491 children (mean [SD] age, 5.6 [3.3] years; 261 [53%] male and 230 [47%] female). Following cataract extraction with primary IOL implantation, a frequent complication was surgery for visual axis opacification (VAO) (cumulative incidence, 32%; 95% CI, 27%-36%). Cumulative incidence was lower with anterior vitrectomy at the time of IOL placement (12%; 95% CI, 8%-16%) vs without (58%; 95% CI, 50%-65%), and the risk of undergoing surgery for VAO was associated with not performing anterior vitrectomy (hazard ratio [HR], 6.19; 95% CI, 3.70-10.34; P &amp;lt; .001). After adjusting for anterior vitrectomy at lens surgery, there were no differences in incidence of surgery for VAO by age at surgery (&amp;lt;2 years, HR, 1.35 [95% CI, 0.63-2.87], 2 to &amp;lt;4 years, HR, 0.86 [95% CI, 0.44-1.68], 4 to &amp;lt;7 years, HR, 1.06 [95% CI, 0.72-1.56]; P = .74) or by capsular bag vs sulcus IOL fixation (HR, 1.22; 95% CI, 0.36-4.17; P = .75). Cumulative incidence of glaucoma plus glaucoma suspect by 5 years was 7% (95% CI, 4%-9%), which did not differ by age after controlling for IOL location and laterality. Conclusions and Relevance In this cohort study, a frequent complication following pediatric lensectomy with primary IOL was surgery for VAO, which was associated with primary anterior vitrectomy not being performed but was not associated with age at surgery or IOL location. The risk of glaucoma development across all ages at surgery suggests a need for long-term monitoring.
Incidence of Glaucoma-Related Adverse Events in the First 5 Years After Pediatric Lensectomy
Bothun, Erick D. , Repka, Michael X. , Kraker, Raymond T. , Leske, David A. , Li, Zhuokai , Astle, William F., Holmes, Jonathan M. , Group, Pediatric Eye Disease Investigator, Wallace, David K. , Enyedi, Laura B. , Jones, Sarah K., Hug, Denise, Stahl, Erin D., Dent, Rebecca J., Kong, Lingkun , Wang, Serena , Gallerson, Bryan K., Hutchinson, Amy K., Lenhart, Phoebe D. , Brower, Judy, Morrison, David G., Ruark, Scott T., Mets-Halgrimson, Rebecca, Yoon, Hawke , Hamidullah, Aaliyah, Anderson, Jill S., Holleschau, Ann M., Superstein, Rosanne , Bélanger, Caroline, Fallaha, Nicole, Hamel, Patrick , Thibeault, Maryse, Tamkins, Susanna M. , Park, Hee-Jung S., Trumler, Anya A., Liu, Xiaonong, Sanders, Emi , McOwen, Diana C., Gray, Michael E. , Yang, Michael B. , Bowman, Corey S., Galvin, Jennifer, Therriault, Margaret, Smith, Heather , Whitaker, Michele E., Örge, Faruk , Grigorian, A. Paula, Baird, Alicia M., Strominger, Mitchell B. , Klein, Shelley, Kemmer, Jacquelyn D., Neiman, Alexandra E., Mendoza, Myra N., Frohwein, Jill J., Bremer, Don L., Cassady, Cybil, Golden, Richard P., Jordan, Catherine O., Oravec, Sara A., Yanovitch, Tammy L. , Lunsford, Keven, Nye, Christina, Shea, Caroline, Stillman, SueAnn M., Iderstine, Stephen C. Van, Robertson, Elisa, Cruz, Oscar A., Ghadban, Rafif, Govreau, Dawn, Longmuir, Susannah Q. , Shan, Xiaoyan, Taylor, Kate , Powell, Christine, Hammond, Benjamin P., Gearinger, Matthew D., Czubinski, Andrea, Salvin, Jonathan, Fisher, Alicia, Lee, Katherine A., Brooks, Daniel , Schweinler, Bonita R., Sala, Nicholas A., Sala, Allyson M., Summers, Allison I. , Karr, Daniel J. , Wilson, Lorri B., Rauch, Paula K., O’Hara, Mary, Gandhi, Nandini, Hashmi, Tania, Colburn, Jeffrey, Dittman, Eileen, Whitfill, Charles R., Wheeler, Amy M., McCourt, Emily A. , Singh, Jasleen , Welnick, Nanastasia, Azar, Nathalie F., Baker, Joseph, Droste, Patrick J. , Peters, Robert J., Hilbrands, Jan, Pineles, Stacy L., Bernardo, Marianne J., Peterson, Edward, Peterson, Charla H., Kumar, Kartik , Melese, Ephrem, Lingua, Robert W., Grijalva, Jeff, Crouch, Earl R., Crouch, Earl R., Ventura, Gaylord, Anninger, William, Benson, Shawn L., Karp, Karen A. , Smith, Jordana M., Brickman-Kelleher, Jill, Ticho, Benjamin H., Khammar, Alexander J., Clausius, Deborah A., Guo, Suquin, Chamberlain, Carolyn, Schloff, Susan, Madigan, William P., Burkman, Donna, Ramsey, Jean E., McConnell, Kate H. , Friedman, Ilana, Rosado, José , Sauberan, Donald P., Hemberger, Jody C., Davis, Patricia L., Rudaitis, Indre, Lowery, Robert S., Cupit, Shawn, Mohney, Brian G., Wernimont, Suzanne M., Neilsen, Rebecca A., Baran, Francine, Gladstone, Amy, Smith, Justin , Mellott, Mei, Kieser, Troy, Erzurum, S. Ayse , Colon, Beth, Shah, Birva, Quebbemann, Micaela, Austin, Darrell S., Boyle, Nicole M., Conner, Courtney L., Chandler, Danielle L. , Donahue, Quayleen, Fimbel, Brooke P., Robinson, Julianne L., Hercinovic, Amra, Hoepner, James E., Kaplon, Joseph D., Melia, Michele , Ortiz, Gillaine, Woodard, Victoria C., Stutz, Kathleen M., Sutherland, Desirae R. , Everett, Donald F., Diener‐West, Marie , Baker, John D., Davis, Barry R. , Phelps, Dale L. , Poff, Stephen W., Tychsen, Lawrence , Bradfield, Yasmin S., Foster, Nicole C. , Plager, David A. , Salchow, Daniel J. , Silver, Jayne L., Weise, Katherine K., Verderber, Lisa C. , Dean, Trevano W., Yen, Kimberly G., Campomanes, Alejandra G. de Alba , Young, Marielle P. , Rahmani, Bahram , Haider, Kathryn M. , Whitehead, George F., Lambert, Scott R. , Kurup, Sudhi P. , Kraus, Courtney L. , Wu, Rui, Hatt, Sarah R. , Freedman, Sharon F. , Cotter, Susan A. , Group, Pediatric Eye Disease Investigator, Prakalapakorn, Sasapin Grace , Ranaivo, Hantamalala Ralay , Areaux, Raymond G. , Chang, Ta Chen , Traboulsi, Elias I. , Ghasia, Fatema F. , Chen, Vicki, Rogers, David L. , LaRoche, G. Robert, Larson, Scott A. , Clarke, Michael W. , Hendricks, Dorothy H. , Jin, Jing , Brooks, Daniel, Rauch, Paula K., Baker, Joseph, Peterson, Edward, Crouch, Earl R., Suh, Donny Won , Christiansen, Stephen P. , Herlihy, Erin P. , Beck, Roy W. , Henderson, Robert J. , Saunders, Richard Anthony , Birch, Eileen E. , Manny, Ruth E. , Holmes, Jonathan M.

JAMA Ophthalmology | February 16, 2023 | Volume: 141 | Issue: 4 | Pages: 324

10.1001/jamaophthalmol.2022.6413 | PMID 36795393 Get It

ImportanceGlaucoma can develop following cataract removal in children.ObjectiveTo assess the cumulative incidence of glaucoma-related adverse events (defined as glaucoma or glaucoma suspect) and factors associated with risk of these adverse events in the first 5 years after lensectomy prior to 13 years of age.Design, Setting, and ParticipantsThis cohort study used longitudinal registry data collected at enrollment and annually for 5 years from 45 institutional and 16 community sites. Participants were children aged 12 years or younger with at least 1 office visit after lensectomy from June 2012 to July 2015. Data were analyzed from February through December 2022.ExposuresUsual clinical care after lensectomy.Main Outcomes and MeasuresThe main outcomes were cumulative incidence of glaucoma-related adverse events and baseline factors associated with risk of these adverse events.ResultsThe study included 810 children (1049 eyes); 443 eyes of 321 children (55% female; mean [SD] age, 0.89 [1.97] years) were aphakic after lensectomy, and 606 eyes of 489 children (53% male; mean [SD] age, 5.65 [3.32] years) were pseudophakic. The 5-year cumulative incidence of glaucoma-related adverse events was 29% (95% CI, 25%-34%) in 443 eyes with aphakia and 7% (95% CI, 5%-9%) in 606 eyes with pseudophakia; 7% (95% CI, 5%-10%) of aphakic eyes and 3% (95% CI, 2%-5%) of pseudophakic eyes were diagnosed as glaucoma suspect. Among aphakic eyes, a higher risk for glaucoma-related adverse events was associated with 4 of 8 factors, including age less than 3 months (vs ≥3 months: adjusted hazard ratio [aHR], 2.88; 99% CI, 1.57-5.23), abnormal anterior segment (vs normal: aHR, 2.88; 99% CI, 1.56-5.30), intraoperative complications at time of lensectomy (vs none; aHR, 2.25; 99% CI, 1.04-4.87), and bilaterality (vs unilaterality: aHR, 1.88; 99% CI, 1.02-3.48). Neither of the 2 factors evaluated for pseudophakic eyes, laterality and anterior vitrectomy, were associated with risk of glaucoma-related adverse events.Conclusions and RelevanceIn this cohort study, glaucoma-related adverse events were common after cataract surgery in children; age less than 3 months at surgery was associated with elevated risk of the adverse events in aphakic eyes. Children with pseudophakia, who were older at surgery, less frequently developed a glaucoma-related adverse event within 5 years of lensectomy. The findings suggest that ongoing monitoring for the development of glaucoma is needed after lensectomy at any age.
Relationships among Clinical Factors and Patient‐reported Outcome Measures in Adults with Convergence Insufficiency
Lorenzana, Ingryd J., Leske, David A. , Dean, Trevano W., Jenewein, Erin C. , Dagi, Linda R. , Beal, Casey J. , Retnasothie, Dashaini V., Esposito, Christina , Erzurum, S. Ayse , Aldrich, Amy E., Crouch, Eric R. , Li, Zhuokai , Kraker, Raymond T. , Holmes, Jonathan M. , Group, The Pediatric Eye Disease Investigator, Larson, Scott A. , Miller, Aaron M. , Hatt, Sarah R. , Pang, Yi , Cotter, Susan A. , Group, The Pediatric Eye Disease Investigator, Holmes, Jonathan M.

Optometry and Vision Science | August 1, 2022 | Volume: 99 | Issue: 9 | Pages: 692-701

10.1097/opx.0000000000001929 | PMID 35914096 Get It

SIGNIFICANCE When exploring relationships among clinical measures and patient‐reported outcome measures in adults with convergence insufficiency, worse symptoms (Convergence Insufficiency Symptom Survey [CISS] score) seemed to be correlated with worse reading function domain score (Adult Strabismus‐20 quality‐of‐life questionnaire). After treatment, improved symptoms were associated with improved reading function quality of life. PURPOSE This study aimed to explore relationships between clinical measures and patient‐reported outcome measures in adults undergoing treatment for symptomatic convergence insufficiency. METHODS In a prospective multicenter observational study, we evaluated adults with symptomatic convergence insufficiency (i.e., clinical measures of near exodeviation, receded near point of convergence, reduced near positive fusional vergence; CISS score ≥21). Fifty‐seven participants treated with vision therapy/exercises (n = 35) or base‐in prism (n = 22) were analyzed. Spearman correlation coefficients ( R ) were used to assess associations among the three clinical measures and patient‐reported outcome measures (CISS, Diplopia Questionnaire, four Adult Strabismus‐20 quality‐of‐life domains) before treatment (baseline) and after 10 weeks and 1 year. Associations were interpreted to be present when the lower limit of the 95% confidence interval (CI) was moderate to strong ( R ≥ 0.4). RESULTS Among multiple exploratory analyses, the only moderate to strong baseline correlation was between worse CISS and worse Adult Strabismus‐20 reading function scores ( R = 0.62; 95% CI, 0.43 to 0.76). Regarding change in measures with treatment, the only moderate to strong correlations were between improved CISS and improved Adult Strabismus‐20 reading function scores for prism at 10 weeks ( R = 0.78; 95% CI, 0.52 to 0.91) and 1 year ( R = 0.85; 95% CI, 0.65 to 0.94) and for vision therapy/exercises at 1 year ( R = 0.78; 95% CI, 0.57 to 0.89). CONCLUSIONS In exploratory analyses, we found positive correlations between CISS symptom scores and reading function quality‐of‐life scores. The absence of correlations between symptoms and individual clinical measures is consistent with clinical experience that, in convergence insufficiency, symptoms and clinical findings can be discordant.
Abstract CT026: The effect of intrinsic subtype on inhibition of tumor growth by anastrozole vs. fulvestrant vs. the combination: Results from the Alliance neoadjuvant endocrine therapy (NET) ALTERNATE trial
Fan, Cheng , Gibbs, Richard A. , Sanati, Souzan , Watson, Mark , Dockter, Travis , Hahn, Olwen, Guenther, Joseph M., Caudle, Abigail S. , Crouch, Erica M. , Tiersten, Amy , Mita, Monica , Razaq, Wajeeha, Leitch, A. Marilyn , Unzeitig, Gary, Winer, Eric, Weiss, Anna , Hunt, Kelly, Cynthia, X. , Ellis, Matthew J. , Anurag, Meenakshi , Hoog, Jeremy , Fernández-Martínez, Aranzazu , Vij, Kiran R , Watson, Mark, Crouch, Erica, Hieken, Tina J. , Wang, Yang , Partridge, Ann H. , Perou, Charles M. , Suman, Vera J. , Carey, Lisa A.

Cancer Research | June 15, 2022 | Volume: 82 | Issue: 12_Supplement | Pages: CT026-CT026

10.1158/1538-7445.am2022-ct026 Get It

Abstract Introduction: The ALTERNATE trial randomized postmenopausal women with ER Allred 6-8 HER2- breast cancer to 6 months of NET with anastrozole (A), fulvestrant (F) or the combination (A+F). Biopsies were taken preNET and after 4-weeks(wks). Patients with Ki67 values &gt;10% at 4-wks were offered triage to neoadjuvant chemotherapy. Patients with on-treatment Ki67 ≤ 10% who completed NET underwent surgery and Ki67 was reassessed. The primary endpoint was endocrine-sensitive disease rate (ESDR). ESD is defined as pCR or PEPI-0 residual disease (pT1-2, pN0, Ki67 ≤ 2.7%). We previously reported that the ESDR difference between the F-containing arms and the A arm was not &gt;10% (ASCO 2020) and that baseline RNA-seq-based intrinsic subtypes predicted outcomes overall (SABCS 2021). Herein we describe relationships between PAM50 intrinsic subtype and Ki67 values by treatment arm because comparative drug effectiveness in adjuvant endocrine therapy studies in ER+ HER2- breast cancer can be predicted by the degree of Ki67 suppression (PMC3518447). Methods: 743 of the 1297 eligible patients (A: 264; F: 231; A+F: 248) had RNA extracted from preNET frozen tumor biopsies with &gt;50% tumor content and subjected to RNA seq. Intrinsic subtypes were then assigned as LumA, LumB, and NonLum (Basal or HER2-E) using open-source PAM50-based informatics. Differences in the proportion with wk4 Ki67 &gt; 10%, % change in wk4 ki67, and surgical CCCA (Ki67 ≤ 2.7%) rate (sxCCCA) between treatments and by intrinsic subtype was assessed using stratified logistic regression, Wilcoxon rank sum test, and Fisher’s exact test, respectively. Analysis of sxCCCA excluded those who failed to complete NET for reasons other than disease progression or early Ki67 &gt;10%. Results: Amongst the 358 LumA cases there were no significant differences in Ki67-based endpoints between treatments. Among the 292 LumB cases, the wk4 ki67 &gt; 10% rate was lower with A+F (19.4%) than A (43%) (P=0.0002) and was somewhat lower in F (31%) versus A (P=0.076). The % change in wk4 Ki67 in LumB cases, adjusted for baseline Ki67, showed markedly superior suppression for A+F versus A (-90% vs. -77%; P=&lt;0.0001) and versus F (-90% vs. -80%; P=0.0026). Furthermore sxCCCA rates were significantly higher with A+F than A (53% vs. 25% P = &lt;0.0001) and somewhat higher for F (37%) than A (p=0.068), indicating that superior antiproliferative effects for A+F persist after 6 months on therapy. Lack of Ki67 suppression in response to treatment was observed in the majority of 43 NonLum samples regardless of treatment. Conclusion: The combination of A+F was significantly more effective than either drug alone for the control of LumB breast cancer cell proliferation. This suggests that A+F may be a more effective adjuvant endocrine therapy than A alone in LumB disease. The lower Ki67 suppression with A alone also suggests that poorer outcome in some LumB tumors may be due to insufficient ER targeting rather than ER-independent tumor growth Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG), NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org. (MJE) CPRIT RR140033, P50-CA186784, P50-CA58223, U01-CA214125, U24-CA210954, Gift from Ralph and Lisa Eads, McNair Scholarship. ClinicalTrials.gov Identifier: NCT01953588 Citation Format: Matthew J. Ellis, Meenakshi Anurag, Jeremy Hoog, Aranzazu Fernandez-Martinez, Cheng Fan, Richard Gibbs, Souzan Sanati, Kiran Vij, Mark Watson, Travis Dockter, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erica Crouch, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J. Hieken, Yang Wang, A. Marilyn Leitch, Gary W. Unzeitig, Eric Winer, Anna Weiss, Kelly Hunt, Ann H. Partridge, Charles M. Perou, Vera Suman, Cynthia X. Ma, Lisa A. Carey. The effect of intrinsic subtype on inhibition of tumor growth by anastrozole vs. fulvestrant vs. the combination: Results from the Alliance neoadjuvant endocrine therapy (NET) ALTERNATE trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT026.
Rasch‐calibrated Intermittent Exotropia Symptom Questionnaire for Children
Holmes, Jonathan M., Leske, David A., Hercinovic, Amra, Hatt, Sarah R., Chandler, Danielle L., Li, Zhuokai, Melia, B. Michele, Chen, Angela M., Erzurum, Sergul Ayse, Crouch, Eric R., Jenewein, Erin C., Kraker, Raymond T., Cotter, Susan A., Group, Pediatric Eye Disease Investigator, Holmes, Jonathan M. , Holmes, Jonathan M., Leske, David A., Hercinovic, Amra, Hatt, Sarah R., Chandler, Danielle L., Li, Zhuokai, Melia, B. Michele, Chen, Angela M., Erzurum, Sergul Ayse, Crouch, Eric R., Jenewein, Erin C., Kraker, Raymond T., Cotter, Susan A., Group, Pediatric Eye Disease Investigator, Holmes, Jonathan M.

Optometry and Vision Science | April 12, 2022 | Volume: 99 | Issue: 6 | Pages: 513-520

10.1097/opx.0000000000001901 | PMID 35412528 Get It

SIGNIFICANCE A rigorously designed and calibrated symptom questionnaire for childhood intermittent exotropia would be useful for clinical care and for research. PURPOSE The aim of this study was to Rasch‐calibrate and evaluate the previously developed Child Intermittent Exotropia Symptom Questionnaire using data gathered as part of a randomized clinical trial. METHODS The questionnaire was administered to 386 children aged 3 to 10 years with intermittent exotropia who were enrolled in a randomized clinical trial comparing overminus with nonoverminus spectacles. Participants were followed at 6 and 12 months while on treatment and at 18 months off treatment. Factor analysis determined dimensionality, and Rasch analysis evaluated questionnaire performance. Logit values were converted to 0 (best) to 100 (worst). We evaluated differences in questionnaire scores between treatment groups and time points, and correlations with control scores. RESULTS The Child Intermittent Exotropia Symptom Questionnaire was unidimensional. Rasch analysis indicated that there was no notable local dependence and no significant differential item functioning for sex or age. There was suboptimal targeting (mean logit, −1.62), and person separation was somewhat poor (0.95). There were no significant differences in the Child Intermittent Exotropia Symptom score between overminus spectacles and nonoverminus spectacles at 6, 12, and 18 months. Combining data from both treatment groups, there was significant improvement from baseline at all follow‐up visits (e.g., mean change from baseline to 12 months, −6.6 points; 95% confidence interval, −8.6 to −4.6). Child Intermittent Exotropia Symptom scores were not correlated with distance or near control scores at 12 months. CONCLUSIONS The seven‐item Rasch‐scored Child Intermittent Exotropia Symptom Questionnaire is limited by suboptimal performance. Future study is needed to determine whether it may be useful for clinical practice and for research.
Abstract PD9-03: Pam50 intrinsic subtype and risk of recurrence score (ROR) for the prediction of endocrine (ET) sensitivity and pathologic response to chemotherapy in postmenopausal women with clinical stage II/III estrogen receptor positive (ER+) and HER
Cynthia, X. , Dockter, Travis , Fernández-Martínez, Aranzazu , Fan, Cheng , Gibbs, Richard A. , Sanati, Souzan , Watson, Mark , Hahn, Olwen, Guenther, Joseph M., Caudle, Abigail S. , Crouch, Erika C., Tiersten, Amy , Mita, Monica , Razaq, Wajeeha, Leitch, A. Marilyn , Unzeitig, Gary, Weiss, Anna , Fernandez-Martinez, Aranzazu , Anurag, Meenakshi , Hoog, Jeremy , Vij, Kiran R , Watson, Mark, Hieken, Tina J. , Wang, Yang , Winer, Eric P. , Hunt, Kelly K. , Partridge, Ann H. , Carey, Lisa A. , Perou, Charles M. , Ellis, Matthew J. , Suman, Vera J.

Cancer Research | March 8, 2022 | Volume: 82 | Issue: 4_Supplement | Pages: PD9-03-PD9-03

10.1158/1538-7445.sabcs21-pd9-03 Get It

Abstract Background: Neoadjuvant ET (NET) offers an opportunity to assess ET sensitivity for ER+ HER2- BC and potentially to tailor therapy. Ki67 &gt;10% on biopsy after 2-4 weeks (wks) of NET identifies patients (pts) with intrinsic ET resistance; while pathologic complete response (pCR) and modified preoperative endocrine prognostic index of 0 (mPEPI 0: pT1-2N0, Ki67 ≤2.7%) at surgery indicates sensitivity to ET. However, on-NET biopsy is not always acceptable or feasible and delays the ET sensitivity determination. PAM50 ROR score and intrinsic subtypes by tumor RNA profiling are prognostic in pts with early stage ER+ HER2- BC, and predict pCR rates to neoadjuvant chemotherapy (NCT) (PMC2667820). We therefore hypothesized that PAM50 analysis on pre-NET biopsies could predict the likelihood of a) a high on-NET Ki67, b) mPEPI-0 or pCR at surgery and, c) pCR for pts triaged to NCT. Methods: The ALTERNATE trial is a phase III study that randomized postmenopausal pts with clinical stage II/III ER+ (Allred score 6-8) HER2- BC to receive neoadjuvant anastrozole, fulvestrant, or both for 6 months before surgery. Research biopsy was required at pre-NET and wk 4, then optional at wk 12. Pts with Ki67 &gt;10% on biopsy at wk 4 or 12 discontinued NET and were offered NCT. PAM50 intrinsic subtype and ROR-P values were generated from mRNA sequencing (RNASeq) analysis on pre-NET biopsies using open-source informatics (PMC7723687) and evaluated for prediction of on-NET Ki67 &gt;10% at wk 4 or 12, pCR or mPEPI-0 post NET, and pCR post NCT. Results: 749 of 1,297 eligible trial pts were included in the analyses, after excluding 548 pts due to insufficient pre-NET tumor for RNASeq (n=511) or PAM50 normal subtype (n=37). Similar to the entire ALTERNATE population, the rate of Ki67 &gt;10% at wk 4 or 12 was 24.4% (95% CI: 21.4-27.7%) and the rate of mPEPI-0/pCR post NET was 19.8% (95% CI: 17.0-22.8%). There were 393 (52.5%) Lum A, 302 (40.3%) Lum B, and 54 (7.2%) non-Lum (9 Basal, 45 HER2-E) BCs. These included 196 (26.2%) ROR-P low, 354 (47.3%) ROR-P medium and 199 (26.6%) ROR-P high BCs. Both the rates of Ki67 &gt;10% at wk 4 or 12 and mPEPI-0/pCR differed significantly with respect to PAM50 subtype or ROR-P category, such that Lum A or ROR-P low BCs were least likely to have a Ki67 &gt;10% at wk 4 or 12 and most likely to achieve mPEPI-0/pCR (Table). 93 of 168 (55.4%) pts triaged to NCT had RNA-seq results, yielding 26 Lum A, 49 Lum B, 4 Basal and 14 HER2-E, with the pCR rates of 0%, 6.1%, 0%, and 21.4%, respectively. There were 10 ROR-P low, 39 medium, and 44 high tumors, with a pCR rate of 0%, 5.1% and 9.1%, respectively. Conclusion: These data indicate that both baseline ROR-P and intrinsic subtype are predictive of early on-NET Ki67 &gt; 10% and mPEPI 0/pCR at surgery after NET. For pts triaged to NCT based on an early on-NET Ki67 &gt;10%, the HER2-E group had the highest pCR rate (20%) and no pCRs were observed in Lum A. These data may be useful for directing neoadjuvant therapy in postmenopausal pts with ER+ HER2- BC. Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG), NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org. (MJE) CPRIT RR140033, P50CA186784, P50-CA58223, U01 CA214125, U24CA210954, Gift from Ralph and Lisa Eads, McNair Scholarship. Trials.gov Identifier: NCT01953588. Table 1.Rates of Ki67 &gt;10% and mPEPI-0/pCR post NET by PAM50 subtype and ROR-P categoryKi67 &gt;10% at wk 4 or 12mPEPI 0/pCR post NETPAM50 SubtypenYes, n (%)PnNo, n (%)PLum A37251 (13.7%) 95% CI: 10.4-17.6%&lt;0.0001393104 (26.5%) 95%CI: 22.2-31.1%&lt;0.0001Lum B29394 (32.1%) 95% CI: 26.8-37.8%30243 (14.2%) 95%CI: 10.5-18.7%Non-luminal (Basal and HER2-E)5338 (71.7%) 95%CI: 57.6-83.2%541 (1.9%) 95%CI: 0.05-9.9%ROR-P CategorynYes, n (%)PnNo, n (%)PLow18018 (10.0%) 95%CI: 6.0-15.3%&lt;0.000119660 (30.6%) 95%CI: 24.2-37.6%&lt;0.0001Intermediate34474 (21.5%) 95%CI: 17.3-26.2%35471 (20.1%) 95%CI: 16.0-24.6%High19491 (46.9%) 95%CI: 39.7-54.2%19917 (8.5%) 95%CI: 5.1-13.3% Citation Format: Cynthia X Ma, Meenakshi Anurag, Travis Dockter, Jeremy Hoog, Aranzazu Fernandez-Martinez, Cheng Fan, Richard Gibbs, Souzan Sanati, Kiran Vij, Mark Watson, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erika Crouch, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, A. Marilyn Leitch, Gary W Unzeitig, Anna Weiss, Eric P Winer, Kelly Hunt, Ann H Partridge, Lisa A Carey, Charles M Perou, Matthew J Ellis, Vera Suman. Pam50 intrinsic subtype and risk of recurrence score (ROR) for the prediction of endocrine (ET) sensitivity and pathologic response to chemotherapy in postmenopausal women with clinical stage II/III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) in the alternate trial (Alliance A011106) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD9-03.