Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies.

BACKGROUND: Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period. MAIN FINDINGS: We conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0-89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13-45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5-28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count < 4000/mL). SHORT CONCLUSION: CP therapy can be considered a potentially effective and relatively safe therapeutic option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors).

Association of Ocular Manifestations of Marfan Syndrome With Cardiovascular Complications.

PURPOSE: To evaluate associations between ocular manifestations of Marfan syndrome and cardiovascular complications. DESIGN: Retrospective cohort study. METHODS: The TriNetX Analytics platform, a federated health research network of aggregated deidentified electronic health record data of more than 119 million patients, was used to identify patients diagnosed with Marfan syndrome. Univariate logistic regression models were used to evaluate the association of ocular manifestations of Marfan syndrome (such as retinal tears/detachment, lens dislocation, and myopia), with cardiovascular comorbidities. Additional sensitivity analyses were performed using propensity matching. Odds ratios and 95% CIs were calculated for incidence of cardiovascular comorbidities (including aortic dissection, valvular disease, and arrhythmias) following diagnosis of Marfan syndrome. RESULTS: A total of 19,105 patients were identified who were diagnosed with Marfan disease without ocular manifestations, and an additional 3887 Marfan patients with ocular comorbidities. Patients who were diagnosed with ocular disease included 883 with ectopic lens, 417 with retinal tear or detachment, 683 with aphakia, 534 with pseudophakia, and 2465 with myopia. Patients with any ocular manifestations of Marfan were significantly more likely to be diagnosed with all cardiovascular comorbidities modeled including aortic aneurysm and dissection (OR 2.035; P < .0001), mitral valve prolapse (OR 2.725; P < .0001), tricuspid valve disorders (OR 2.142; P < .0001), cardiac arrhythmias (OR 1.836; P < .0001), and all cardiovascular outcomes combined (OR 2.194; P < .0001). CONCLUSIONS: In a large and diverse cohort of patients with Marfan syndrome, ocular manifestations of the disorder appear strongly associated with cardiovascular comorbidities.

Reporting Requirements, Confidentiality, and Legal Immunity for Physicians Who Report Medically Impaired Drivers.

Importance: Physicians play an important role in assessing patients' ability to drive. There is a dearth of peer-reviewed information on policies regarding physician reporting of medically impaired drivers. Objective: To investigate state reporting requirements and the availability of confidentiality and legal immunity for physicians who report medically impaired drivers. Design, Setting, and Participants: This cross-sectional study was conducted from November 1 to 30, 2022, in 3 rounds. First, all 50 US states' Department of Motor Vehicle (DMV) websites were systematically reviewed. Second, DMV staff from each state were surveyed via telephone. Third, each state's legal codes for driver licensing were reviewed. Main Outcomes and Measures: Outcome measures included the percentage of states with mandatory and voluntary reporting policies, reporting instructions on DMV websites, anonymous reporting options, and legal immunity for reporting physicians, in addition to characteristics of states' mandatory reporting policies (ie, types of medical conditions that require reporting) and policies surrounding the confidentiality of reports. The data were analyzed using descriptive statistics. Results: One-third of state DMV websites (17 [34%]) lacked instructions regarding physician reporting. Six states had mandatory reporting requirements; 4 of these states only required reporting of conditions characterized by lapses of consciousness. Only 3 states (6%) accepted anonymous reports, and 7 states (14%) deemed physician reports of medically impaired drivers confidential without exception. Nearly one-third of states (15 [30%]) deemed reports by physicians confidential, with the exception that reported drivers could find out who reported them if they asked for a copy of the reporting form. Most states (37 [74%]) had statutes that protected physicians from liability related to reporting medically impaired drivers. Conclusions and Relevance: This cross-sectional study of state reporting requirements regarding medically impaired drivers found many differences in state policies regarding mandatory reporting and the conditions that require reporting. There was also limited availability of online reporting instructions, anonymous reporting options, and legal protections for reporting physicians.

Multiomic Single Cell Sequencing Identifies Stemlike Nature of Mixed Phenotype Acute Leukemia and Provides Novel Risk Stratification.

Mixed phenotype acute leukemia (MPAL) is a leukemia whose biologic drivers are poorly understood, therapeutic strategy remains unclear, and prognosis is poor. We performed multiomic single cell (SC) profiling of 14 newly diagnosed adult MPAL patients to characterize the immunophenotypic, genetic, and transcriptional landscapes of MPAL. We show that neither genetic profile nor transcriptome reliably correlate with specific MPAL immunophenotypes. However, progressive acquisition of mutations is associated with increased expression of immunophenotypic markers of immaturity. Using SC transcriptional profiling, we find that MPAL blasts express a stem cell-like transcriptional profile distinct from other acute leukemias and indicative of high differentiation potential. Further, patients with the highest differentiation potential demonstrated inferior survival in our dataset. A gene set score, MPAL95, derived from genes highly enriched in this cohort, is applicable to bulk RNA sequencing data and was predictive of survival in an independent patient cohort, suggesting utility for clinical risk stratification.

The Volume-Cost Relationship: How Does Surgical Volume Affect Cost and Value in AIS Surgery.

STUDY DESIGN: Retrospective review. OBJECTIVE: The objective of this study was to evaluate and compare distribution of hospital and operating room charges and outcomes during posterior spinal fusion for adolescent idiopathic scoliosis (AIS) patients by high-volume (HV) and standard-volume (SV) surgeons at one institution and examine potential cost savings. SUMMARY OF BACKGROUND DATA: Increased surgical volume has been associated with improved perioperative outcomes after spinal deformity correction. However, there is a lack of information on how this may affect hospital costs. METHODS: Retrospective study of AIS patients undergoing posterior spinal fusion between 2013 and 2019. Demographic, x-ray, chart review and hospital costs were collected and compared between HV surgeons (≥50 AIS cases/y) and SV surgeons (<50/y). Comparative analyses were computed using Wilcoxon rank-sum, Kruskal-Wallis, and the Fisher exact tests. Average values with corresponding minimum-maximum rages were reported. RESULTS: A total of 407 patients (HV: 232, SV: 175) operated by 4 surgeons (1 HV, 3 SV). Radiographic parameters were similar between the groups. HV surgeons had significantly lower estimated blood loss (385.3 vs. 655.6 mL, P <0.001), fewer intraoperative transfusions (10.8% vs. 25.1%, P <0.001), shorter surgery time (221.6 vs. 324.9 min, P <0.001), and lower radiation from intraoperative fluoroscopy (4.4 vs. 6.4 mGy, P <0.001). HV patients had a significantly lower length of stay (4.3 vs. 5.3, P <0.001) and complication rate (0.4% vs. 4%, P =0.04).HV surgeons had significantly lower total costs ($61,716.24 vs. $72,745.93, P <0.001). This included lower transfusion costs ( P <0.001), operative time costs ( P <0.001), screw costs ( P <0.001), hospital stay costs ( P <0.001), and costs associated with 30-day emergency department returns ( P <0.001). CONCLUSION: HV surgeons had significantly lower operative times, lower estimated blood loss and transfusion rates and lower perioperative complications requiring readmission or return to emergency department resulting in lower health care costs. LEVEL OF EVIDENCE: Level III.

Lower-Extremity Segment-Length Prediction Accuracy of the Sanders Multiplier, Paley Multiplier, and White-Menelaus Formula.

BACKGROUND: Several methods are available to estimate leg lengths at maturity to facilitate the determination of timing of epiphysiodesis. We compared the Paley multiplier, Sanders multiplier, and White-Menelaus methods in an epiphysiodesis-aged cohort. We assessed intra- and interrater reliability for Sanders skeletal stages and Greulich and Pyle atlas skeletal age. METHODS: Actual growth was recorded in healthy, unoperated femoral and tibial segments from an epiphysiodesis database. The predicted and actual lengths were compared with use of the Paley multiplier and White-Menelaus methods, Greulich and Pyle skeletal age, and the Sanders multiplier using Sanders stages. Intra- and interrater reliability were assessed in a separate group of 76 skeletal age films. RESULTS: The cohort included 148 femora and 195 tibiae in 197 patients. Femoral length at maturity was slightly underestimated by the Sanders multiplier and staging, was overestimated by the Paley multiplier and skeletal age, and was most accurately predicted with use of the White-Menelaus formula and skeletal age. All methods overestimated tibial length at maturity. The whole-leg prediction accuracy of the Sanders multiplier and White-Menelaus formula were comparable and were more accurate than that of the Paley multiplier. For Sanders skeletal staging, the interrater reliability varied from 0.86 to 0.88 and the intrarater reliability varied from 0.87 to 0.96. For Greulich and Pyle skeletal age, the interrater reliability varied from 0.87 to 0.89 and the intrarater reliability varied from 0.91 to 0.95. CONCLUSIONS: Use of the Sanders multiplier and skeletal stages was more accurate than the Paley multiplier and skeletal age in this cohort. Use of the White-Menelaus formula and skeletal age was slightly more accurate in predicting femoral length and slightly less accurate in predicting tibial length compared with the Sanders multiplier. Intra- and interrater reliability were similar between Sanders skeletal stages and Greulich and Pyle atlas skeletal age. The White-Menelaus formula and skeletal age was the recommended method for predicting lower-extremity segment lengths at maturity and epiphysiodesis effect. Although easier to recall without referencing an atlas and not sex-specific, Sanders skeletal staging does not correspond directly to years of growth remaining, and thus cannot be used with the White-Menelaus formula. CLINICAL RELEVANCE: The Greulich and Pyle atlas to determine skeletal age and the White-Menelaus formula to determine growth remaining are reliable predictors of epiphysiodesis effect in the lower extremities.

Injectable Myocardial Matrix Hydrogel Mitigates Negative Left Ventricular Remodeling in a Chronic Myocardial Infarction Model.

A first-in-man clinical study on a myocardial-derived decellularized extracellular matrix hydrogel suggested the potential for efficacy in chronic myocardial infarction (MI) patients. However, little is understood about the mechanism of action in chronic MI. In this study, the authors investigated the efficacy and mechanism by which the myocardial matrix hydrogel can mitigate negative left ventricular (LV) remodeling in a rat chronic MI model. Assessment of cardiac function via magnetic resonance imaging demonstrated preservation of LV volumes and apical wall thickening. Differential gene expression analyses showed the matrix is able to prevent further negative LV remodeling in the chronic MI model through modulation of the immune response, down-regulation of pathways involved in heart failure progression and fibrosis, and up-regulation of genes important for cardiac muscle contraction.

The Ponseti Method for the Treatment of Clubfeet Associated With Amniotic Band Syndrome: A Single Institution 20-Year Experience.

BACKGROUND: Amniotic band syndrome (ABS) is a congenital disorder resulting in fibrous bands that can cause limb anomalies, amputations, and deformities. Clubfoot has been reported in up to 50% of patients with ABS. The purpose of this study is to compare treatment characteristics and outcomes of clubfoot patients with ABS to those with idiopathic clubfoot treated with the Ponseti method. METHODS: An Institution Review Board (IRB) approved retrospective review of prospectively gathered data was performed at a single pediatric hospital over a 20-year period. Patients with either idiopathic clubfeet or clubfeet associated with concomitant ABS who were <1 year of age and treated by the Ponseti method were included. Initial Dimeglio score, number of casts, need for heel cord tenotomy, recurrence, and need for further surgery were recorded. Outcomes were classified as "good" (plantigrade foot±heel cord tenotomy), "fair" (need for a limited procedure), or "poor" (need for a full posteromedial release). RESULTS: Forty-three clubfeet in 32 patients with ABS, and 320 idiopathic clubfeet in 215 patients were identified. Average age at last follow up was not different between ABS and idiopathic cohorts (7.4 vs. 5.2 y, P=0.233). Average Dimeglio score was lower in the ABS cohort (12.3 vs. 13.7, P=0.006). Recurrence rate was significantly higher in the ABS (62.8%) compared with idiopathic cohort (37.2%) (P=0.001). Clinical outcomes were significantly better in the idiopathic cohort (69.4% "good", 26.9% "fair", 3.8% "poor") compared with the ABS cohort (41.9% "good", 34.9% "fair", and 23.3% "poor") (P<0.001). Within the ABS cohort, no significant differences in clinical outcomes were found based upon location, severity, or presence of an ipsilateral lower extremity band. CONCLUSION: Clubfeet associated with ABS have higher rates of recurrence, a greater need for later surgery, and worse clinical outcomes than idiopathic clubfeet. This information may prove helpful in counseling parents of infants with ABS associated clubfeet. LEVEL OF EVIDENCE: Level III.

Risk of Retinal Artery Occlusion in Patients with Migraine.

PURPOSE: We sought to determine if migraine is associated with increased risk of retinal artery occlusion (RAO). DESIGN: Retrospective cohort study. METHODS: We reviewed a large insurance claims database for patients with migraine and matched control subjects without migraine between 2007 and 2016. Cox proportional hazard regression models were used to investigate the association between migraine and risk of all RAO, central RAO (CRAO), branch RAO (BRAO), and "other" RAO, which includes transient and partial RAO. Primary outcome measures included the incidence of all RAO, including CRAO, BRAO, and other RAO, after first migraine diagnosis. RESULT: There were 418,965 patients with migraine who met the study criteria and were included in the analysis with the appropriate matched control subjects. Among the 418,965 patients with migraine, 1060 (0.25%) were subsequently diagnosed with RAO, whereas only 335 (0.08%) of the patients without migraine were diagnosed with RAO. The hazard ratio (HR) for incident all RAO in patients with migraine compared with those without migraine was 3.48 (95% confidence interval [CI] 3.07-3.94; P < .0001). This association was consistent across all types of RAO, including CRAO (HR 1.62 [95% CI 1.15-2.28]; P = .004), BRAO (HR 2.09 [95% CI 1.60-2.72]; P < .001), and other types of RAO (HR 4.61 [95% CI 3.94-5.38]; P < .001). Patients with migraine with aura had a higher risk for incident RAO compared with those with migraine without aura (HR 1.58 [95% CI 1.40-1.79]; P < .001). This association was consistent for BRAO (HR 1.43 [95% CI 1.04-1.97]; P < .03) and other types of RAO (HR 1.67 [95% CI 1.45-1.91]; P < .001) but was not statistically significant for CRAO (HR 1.18 [95% CI 0.75-1.87]; P = .475). Significant risk factors for this association included increased age, male sex, acute coronary syndrome, valvular disease, carotid disease, hyperlipidemia, hypertension, retinal vasculitis or inflammation, and systemic lupus erythematosus. CONCLUSIONS: Migraine is associated with increased risk of all types of RAO and migraine with aura is associated with increased risk of RAO compared with migraine without aura.

A Prospective Comparison of Wavefront-Guided LASIK versus Wavefront-Guided PRK After Previous Keratorefractive Surgery.

PURPOSE: To compare the results of retreatment with wavefront-guided LASIK versus wavefront-guided PRK for residual refractive error following previous myopic keratorefractive surgery. METHODS: In this prospective study, 32 eyes of 28 patients after prior myopic keratorefractive surgery underwent retreatment with flap-lift wavefront-guided LASIK (n = 12) or wavefront-guided PRK (n = 20) for residual refractive error. Safety, efficacy, predictability, and wavefront outcomes were evaluated. RESULTS: At last follow-up, both LASIK and PRK retreatment resulted in similar improvement in visual acuity with respective mean ± standard deviation (SD) uncorrected distance visual acuity of -0.07 ± 0.11 logMAR and -0.06 ± 0.13 logMAR (p = 0.87). In the study, 16.7% of LASIK and 33.3% of PRK eyes gained one or more lines of best-corrected distance visual acuity (CDVA), while 16.7% and 9.5% of eyes lost one or more lines of CDVA with LASIK and PRK, respectively. One hundred % of LASIK eyes and 89.5% of PRK eyes were within ± 0.50 diopters of emmetropia. Wavefront analysis demonstrated similar reductions in total RMS error higher-order aberrations (p = 0.84) with no difference in coma, trefoil, or spherical aberration between eyes undergoing LASIK or PRK retreatment. CONCLUSION: Wavefront-guided LASIK and wavefront-guided PRK following previous keratorefractive surgery demonstrate similar safety, efficacy, and predictability with comparable wavefront outcomes.

Refractive Outcomes for Cataract Surgery With Toric Intraocular Lenses at a Veterans Affairs Medical Center.

Background: Refractive outcomes for cataract surgery with toric intraocular lenses (IOLs) are not well described in a teaching hospital setting. This study investigated the refractive outcomes of cataract surgery with toric IOLs at an academic-affiliated Veterans Affairs Medical Center (VAMC) and compared the accuracy of 2 biometric formulae for toric IOL power calculation. Methods: A retrospective chart review of patients who received cataract surgery with toric IOLs from November 2013 to May 2018 was conducted. The Holladay 2 and Barrett toric IOL formulae were used to predict the postoperative refraction for each cataract surgery. The main outcome measures were best-corrected visual acuity (BCVA) and the difference in cylinder between the preoperative and postoperative manifest refractions. The accuracy of each biometric formula was also assessed using 2-tailed t tests of the mean absolute error, and subgroup analyses were conducted for short, medium, and long eyes. Results: Of 325 charts reviewed, 283 patients met the inclusion criteria; 87% (248/283) of these surgeries were performed by resident surgeons. The median postoperative BCVA was 20/20, and 92% of patients had a postoperative BCVA of 20/25 or better. There was no statistically significant difference in mean absolute error between the 2 formulae for the entire axial length range (P = .21), as well as the short (P = .94), medium (P = .49), and long axial length (P = .08) groups. Conclusions: To our knowledge, this is the largest study that compared the performance of the Barrett toric and Holladay 2 formulae and the first that made the comparison in a teaching hospital setting. This study suggests that the 2 formulae have similar refractive outcomes across all axial lengths.

The prevalence of preoperative medical testing and consultation in cataract surgery patients at a teaching hospital.

PURPOSE: To investigate the prevalence of preoperative cataract surgery testing and consultation at a single United States teaching hospital. SETTING: Academic-affiliated Veterans Affairs Medical Center. DESIGN: Retrospective chart review. METHODS: This study included patients who received cataract surgery from 2014 to 2018. For patients with bilateral cataracts, the second surgery was excluded to ensure independent selection. Charlson Comorbidity Index (CCI) scores and heart disease status were recorded. The outcomes of interest were preoperative testing, such as complete blood count, chemistry panel, and echocardiography, and consultation (office visits to non-ophthalmologists) during the period between the date the decision was made to proceed with surgery and the cataract surgery date. RESULTS: For this study 1320 charts were reviewed; 1257 (95.2%) patients met the study criteria. The mean CCI score was 1.7; 42.0% (528/1257) had heart disease. The prevalence of preoperative testing was 0.08% (1/1257). The prevalence of preoperative consultation was 4.2% (53/1257); 86.8% (46/53) of patients received cardiology consultation; 17.0% (9/53) pulmonology; and 15.1% (8/53) primary care. Of the patients who received cardiac consultation, 63.0% (29/46) had heart disease; the remaining had an electrocardiogram abnormality. CONCLUSIONS: There was a low prevalence of preoperative testing and consultation for cataract surgery at this teaching hospital. Further studies using medical record data are needed to assess the current rates and the role of preoperative testing and consultation for cataract surgery patients.

Association of Visual Impairment With Risk of Incident Dementia in a Women's Health Initiative Population.

Importance: Dementia affects a large and growing population of older adults. Although past studies suggest an association between vision and cognitive impairment, there are limited data regarding longitudinal associations of vision with dementia. Objective: To evaluate associations between visual impairment and risk of cognitive impairment. Design, Setting, and Participants: A secondary analysis of a prospective longitudinal cohort study compared the likelihood of incident dementia or mild cognitive impairment (MCI) among women with and without baseline visual impairment using multivariable Cox proportional hazards regression models adjusting for characteristics of participants enrolled in Women's Health Initiative (WHI) ancillary studies. The participants comprised community-dwelling older women (age, 66-84 years) concurrently enrolled in WHI Sight Examination (enrollment 2000-2002) and WHI Memory Study (enrollment 1996-1998, ongoing). The study was conducted from 2000 to the present. Exposures: Objectively measured visual impairment at 3 thresholds (visual acuity worse than 20/40, 20/80, or 20/100) and self-reported visual impairment (determined using composite survey responses). Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs for incident cognitive impairment after baseline eye examination were determined. Cognitive impairment (probable dementia or MCI) was based on cognitive testing, clinical assessment, and centralized review and adjudication. Models for (1) probable dementia, (2) MCI, and (3) probable dementia or MCI were evaluated. Results: A total of 1061 women (mean [SD] age, 73.8 [3.7] years) were identified; 206 of these women (19.4%) had self-reported visual impairment and 183 women (17.2%) had objective visual impairment. Forty-two women (4.0%) were ultimately classified with probable dementia and 28 women (2.6%) with MCI that did not progress to dementia. Mean post-eye examination follow-up was 3.8 (1.8) years (range, 0-7 years). Women with vs without baseline objective visual impairment were more likely to develop dementia. Greatest risk for dementia was among women with visual acuity of 20/100 or worse at baseline (HR, 5.66; 95% CI, 1.75-18.37), followed by 20/80 or worse (HR, 5.20; 95% CI, 1.94-13.95), and 20/40 or worse (HR, 2.14; 95% CI, 1.08-4.21). Findings were similar for risk of MCI, with the greatest risk among women with baseline visual acuity of 20/100 or worse (HR, 6.43; 95% CI, 1.66-24.85). Conclusions and Relevance: In secondary analysis of a prospective longitudinal cohort study of older women with formal vision and cognitive function testing, objective visual impairment appears to be associated with an increased risk of incident dementia. However, incident cases of dementia and the proportion of those with visual impairment were low. Research is needed to evaluate the effect of specific ophthalmic interventions on dementia.

Comparison of Using One Trabecular Microbypass Stent versus Two during Cataract Surgery at Two Sites: One-Year Follow-Up.

PURPOSE: To compare IOP and ocular hypotensive medication reduction of using one trabecular microbypass stent versus two in patients with open-angle glaucoma. Setting. Palo Alto Veterans Affairs (VA) Hospital and the Byers Eye Institute at Stanford University, Palo Alto, California, USA. DESIGN: Retrospective case series. METHODS: A chart review included patients who underwent trabecular microbypass implantation with cataract surgery in 2015-2017, with at least one-year follow-up. Subjects were divided into two groups by location (always one stent at Stanford versus two stents at the VA). Primary outcome measures included IOP and medication reduction at baseline and 12-month follow-up. RESULTS: 132 subjects (166 eyes) were included. The preoperative IOP was 16.3 ± 3.4 mmHg on 2.6 ± 1.1 medications in the one-stent group (N = 85) and 17.5 ± 3.1 mmHg on 2.7 ± 0.6 medications in the two-stent group (N = 81). There was no significant difference between the two groups (p = 0.06). At the 12-month visit, there was a 13.37% ± 2.93 reduction in IOP in the 1-stent group (p ≤ 0.001) and 13.49% ± 2.69 in the 2-stent group (p ≤ 0.001); both were not significantly different from each other (p = 0.074). At 12 months, there was also a 14.5% reduction in medication use for the 1-stent group and 15.3% reduction in the 2-stent group, both statistically significant from baseline, (p = 0.022 and p = 0.037, respectively). CONCLUSIONS: Implantation with either one or two stents during cataract surgery in patients with glaucoma demonstrated similar IOP and med reduction in both groups between the two sites.

Assessing the Quality of Published Surveys in Ophthalmology.

PURPOSE: Surveys are an important research modality in ophthalmology, but their quality has not been rigorously assessed. This study evaluated the quality of published ophthalmic surveys. METHODS: Three survey methodologists, three senior ophthalmologists, and two research assistants developed a survey evaluation instrument focused on survey development and testing; sampling frame; response bias; results reporting; and ethics. Two investigators used the instrument to assess the quality of all ophthalmic surveys that were published between January 1, 2018 and December 31, 2018; indexed in MEDLINE/PubMed, Embase, and/or Web of Science; contained the search terms "ophthalmology" and "survey" or "questionnaire" in the title and/or abstract; and were available in English. RESULTS: The search identified 626 articles; 60 met the eligibility criteria and were assessed with the survey evaluation instrument. Most surveys (93%; 56/60) defined the study population; 48% (29/60) described how question items were chosen; 30% (18/60) provided the survey for review or described the questions in sufficient detail; 30% (18/60) were pre-tested or piloted; 25% (15/60) reported validity/clinical sensibility testing; 15% (9/60) described techniques used to assess non-response bias; and 63% (38/60) documented review by an institutional review board (IRB). CONCLUSION: The quality of published ophthalmic surveys can be improved by focusing on survey development, pilot testing, non-response bias and institutional review board review. The survey evaluation instrument can help guide researchers in conducting quality ophthalmic surveys and assist journal editors in evaluating surveys submitted for publication.

Accuracy of biometric formulae for intraocular lens power calculation in a teaching hospital.

AIM: To evaluate the accuracy of three commonly used biometric formulae across different axial lengths (ALs) at one United States Veterans Affairs teaching hospital. METHODS: A retrospective chart review was conducted from November 2013 to May 2018. One eye of each patient who underwent cataract surgery with a monofocal intraocular lens (IOL) was included. The range of postoperative follow-up period was from 3wk to 4mo. The Holladay 2, Barrett Universal II, and Hill-Radial Basis Function (Hill-RBF) formulae were used to predict the postoperative refraction for all cataract surgeries. For each formula, we calculated the prediction errors [including mean absolute prediction error (MAE)] and the percentage of eyes within ±0.25 diopter (D) and ±0.5 D of predicted refraction. We performed subgroup analyses for short (AL<22.0 mm), medium (AL 22.0-25.0 mm), and long eyes (AL>25.0 mm). RESULTS: A total of 1131 patients were screened, and 909 met the inclusion criteria. Resident ophthalmologists were the primary surgeons in 710 (78.1%) cases. We found no statistically significant difference in predictive accuracy among the three formulae over the entire AL range or in the short, medium, and long eye subgroups. Across the entire AL range, the Hill-RBF formula resulted in the lowest MAE (0.384 D) and the highest percentage of eyes with postoperative refraction within ±0.25 D (42.7%) and ±0.5 D (75.5%) of predicted. All three formulae had the highest MAEs (>0.5 D) and lowest percentage within ±0.5 D of predicted refraction (<55%) in short eyes. CONCLUSION: In cataract surgery patients at our teaching hospital, three commonly used biometric formulae demonstrate similar refractive accuracy across all ALs. Short eyes pose the greatest challenge to predicting postoperative refractive error.

Characteristics of Ophthalmology Trials Registered in ClinicalTrials.gov, 2007-2018.

PURPOSE: To perform a comprehensive analysis of characteristics of ophthalmology trials registered in ClinicalTrials.gov. DESIGN: Cross-sectional study. METHODS: All 4,203 ophthalmologic clinical trials registered on ClinicalTrials.gov between October 1, 2007, and April 30, 2018, were identified by using medical subject headings (MeSH). Disease condition terms were verified by manual review. Trial characteristics were assessed through frequency calculations. Hazard ratios and 95% confidence intervals were determined for characteristics associated with early discontinuation. RESULTS: The majority of trials were multiarmed (73.6%), single-site (69.4%), randomized (64.8%), and had <100 enrollees (66.3%). A total of 33% used a data-monitoring committee (DMC), and 50.6% incorporated blinding. Other groups (51.6%) were funded by industry, whereas 2.6% were funded by the US National Institutes of Health (NIH). NIH trials were significantly more likely to address oncologic (NIH = 15.5%, Other = 3%, Industry = 1.5%; P < 0.001) or pediatric disease (NIH = 20.9%, Other = 5.9%, Industry = 1.4%; P < 0.001). Industry-sponsored trials (69.6% of phase 3 trials) were significantly more likely to be randomized (Industry = 68.7%, NIH = 58.9%, Other = 60.8%; P < 0.001) and blinded (Industry = 57.2%, NIH = 42.7%, Other = 43.5%; P < 0.001). A total of 359 trials (8.5%) were discontinued early, and 530 trials (12.6%) had unknown status. Trials were less likely to be discontinued if funded by sources other than industry (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.55-0.95; P = 0.021) and/or had a DMC (HR, 0.71; 95% CI, 0.55-0.92; P = 0.010). CONCLUSIONS: Ophthalmology trials in the past decade reveal heterogeneity across study funding sources. NIH trials were more likely to support historically underfunded subspecialties, whereas Industry trials were more likely to face early discontinuation. These trends emphasize the importance of carefully monitored and methodologically sound trials with deliberate funding allocation.

Automated extraction of ophthalmic surgery outcomes from the electronic health record.

OBJECTIVE: Comprehensive analysis of ophthalmic surgical outcomes is often restricted by limited methodologies for efficiently and accurately extracting clinical information from electronic health record (EHR) systems because much is in free-text form. This study aims to utilize advanced methods to automate extraction of clinical concepts from the EHR free text to study visual acuity (VA), intraocular pressure (IOP), and medication outcomes of cataract and glaucoma surgeries. METHODS: Patients who underwent cataract or glaucoma surgery at an academic medical center between 2009 and 2018 were identified by Current Procedural Terminology codes. Rule-based algorithms were developed and used on EHR clinical narrative text to extract intraocular lens (IOL) power and implant type, as well as to create a surgery laterality classifier. MedEx (version 1.3.7) was used on free-text clinical notes to extract information on eye medications and compared to information from medication orders. Random samples of free-text notes were reviewed by two independent masked annotators to assess inter-annotator agreement on outcome variable classification and accuracy of classifiers. VA and IOP were available from semi-structured fields. RESULTS: This study cohort included 6347 unique patients, with 8550 stand-alone cataract surgeries, 451 combined cataract/glaucoma surgeries, and 961 glaucoma surgeries without concurrent cataract surgery. The rule-based laterality classifier achieved 100% accuracy compared to manual review of a sample of operative notes by independent masked annotators. For cataract surgery alone, glaucoma surgery alone, or combined cataract/glaucoma surgeries, our automated extraction algorithm achieved 99-100% accuracy compared to manual annotation of samples of notes from each group, including IOL model and IOL power for cataract surgeries, and glaucoma implant for glaucoma surgeries. For glaucoma medications, there was 90.7% inter-annotator agreement. After adjudication, 85.0% of medications identified by MedEx determined to be correct. Determination of surgical laterality enabled evaluation of pre- and postoperative VA and IOP for operative eyes. CONCLUSION: This text-processing pipeline can accurately capture surgical laterality and implant model usage from free-text operative notes of cataract and glaucoma surgeries, enabling extraction of clinical outcomes including visual acuities, intraocular pressure, and medications from the EHR system. Use of this approach with EHRs to assess ophthalmic surgical outcomes can benefit research groups interested in studying the safety and clinical efficacies of different surgical approaches.

Multimodal Imaging and Functional Testing in a North Carolina Macular Disease Family: Toxoplasmosis, Fovea Plana, and Torpedo Maculopathy Are Phenocopies.

PURPOSE: To describe multimodal imaging and corresponding functional studies in a newly found family with North Carolina macular dystrophy (NCMD). To our knowledge, this is an original report using OCT angiography to evaluate persons with NCMD. DESIGN: A descriptive, retrospective study of a family with NCMD. PARTICIPANTS: A total of 3 participants, representing 3 generations of a single family, each demonstrating a different grade of NCMD, underwent clinical and genetic testing. METHODS: Diagnostic multimodal imaging and functional testing of the retina included color fundus photography, fundus autofluorescence, intravenous fluorescein angiography, spectral-domain OCT and OCT angiography, multifocal electroretinography, full-field electroretinography, and microperimetry. DNA sequencing was performed using Sanger sequencing techniques. MAIN OUTCOME MEASURES: Spectral-domain OCT images, fundus photographs, fundus autofluorescence images, fluorescein angiograms, OCT angiograms, multifocal electroretinography images, full-field electroretinography images, and microperimetry maps. Sanger sequencing was performed for molecular diagnosis. RESULTS: Multimodal imaging helped to demonstrate the nature of the retinal and choroidal lesions in each participant and the extent of visual function. Genetic testing demonstrated the variant 2 point mutation (chromosome 6: 99593111) in the deoxyribonuclease 1 hypersensitivity binding site on chromosome 6q16 causing overexpression of the retinal transcription factor PRDM13. CONCLUSIONS: NCMD has great phenotypic variability, which can be appreciated only by examining multiple family members. To our knowledge, this is an original report that shows a correlation of functional studies with multimodal imaging. These findings are consistent with NCMD being a developmental abnormality of the macula. All layers of the retina and choroid demonstrate maldevelopment and varying degrees of malfunction. Although PRDM13 is expressed in the amacrine cells, we have yet to identify an abnormality specific to this cellular layer. The retinal vasculature appears to be surprisingly well preserved or intact by OCT angiogram compared with that shown in intravenous fluorescein angiograms. OCT angiograms suggest that foveal hypoplasia is a phenocopy of grade 1 NCMD, torpedo maculopathy is a phenocopy of grade 2 NCMD, and in this single family, congenital toxoplasmosis is a phenocopy of grade 3 NCMD.

The route of the visual receptor rhodopsin along the cilium.

The photoreceptor outer segment is the most elaborate primary cilium, containing large amounts of rhodopsin (RHO) in disk membranes that grow from a connecting cilium. The movement of RHO along the connecting cilium precedes formation of the disk membranes. However, the route that RHO takes has not been clearly determined; some reports suggest that it follows an intracellular, vesicular route along the axoneme, possibly as an adaptation for the high load of delivery or the morphogenesis of the disk endomembranes. We addressed this question by studying RHO in cilia of IMCD3 cells and mouse rod photoreceptors. In IMCD3 cilia, fluorescence recovery after photobleaching (FRAP) experiments with fluorescently tagged RHO supported the idea of RHO motility in the ciliary plasma membrane and was inconsistent with the hypothesis of RHO motility within the lumen of the cilium. In rod photoreceptors, FRAP of RHO-EGFP was altered by externally applied lectin, supporting the idea of plasmalemmal RHO dynamics. Quantitative immunoelectron microscopy corroborated our live-cell conclusions, as RHO was found to be distributed along the plasma membrane of the connecting cilium, with negligible labeling within the axoneme. Taken together, the present findings demonstrate RHO trafficking entirely via the ciliary plasma membrane.This article has an associated First Person interview with the first author of the paper.