AXIN1 bi-allelic variants disrupting the C-terminal DIX domain cause craniometadiaphyseal osteosclerosis with hip dysplasia.

Sclerosing skeletal dysplasias result from an imbalance between bone formation and resorption. We identified three homozygous, C-terminally truncating AXIN1 variants in seven individuals from four families affected by macrocephaly, cranial hyperostosis, and vertebral endplate sclerosis. Other frequent findings included hip dysplasia, heart malformations, variable developmental delay, and hematological anomalies. In line with AXIN1 being a central component of the ß-catenin destruction complex, analyses of primary and genome-edited cells harboring the truncating variants revealed enhanced basal canonical Wnt pathway activity. All three AXIN1-truncating variants resulted in reduced protein levels and impaired AXIN1 polymerization mediated by its C-terminal DIX domain but partially retained Wnt-inhibitory function upon overexpression. Addition of a tankyrase inhibitor attenuated Wnt overactivity in the AXIN1-mutant model systems. Our data suggest that AXIN1 coordinates the action of osteoblasts and osteoclasts and that tankyrase inhibitors can attenuate the effects of AXIN1 hypomorphic variants.

Acute Pelvic and Hip Apophyseal Avulsion Fractures in Adolescents: A Summary of 719 Cases.

BACKGROUND: Apophyseal avulsion fractures of the pelvis and hip are common injuries in adolescent athletes. However, high volume comparative studies elucidating the spectrum of injuries are largely absent from the literature. The current study provides a comprehensive analysis of demographic, anatomic, pathophysiological, clinical, and athletic-related variables associated with such injuries in an extensive population of affected adolescents. METHODS: A retrospective review was performed of records of patients presenting to a single tertiary care pediatric hospital between January 1, 2005, and July 31, 2020, collecting variables including patient sex, age, body mass index, fracture location, injury mechanism, sport at the time of injury, and duration of prodromal symptoms. RESULTS: Seven hundred nineteen fractures were identified in 709 patients. The average patient age was 14.6, and 78% of the fractures occurred in male patients. The anterior inferior iliac spine (33.4%), anterior superior iliac spine (30.5%), and ischial tuberosity (19.4%) were the most common fracture sites. The most common injury mechanisms were running (27.8%), kicking (26.7%), and falls (8.8%). The most common sports at the time of injury were soccer (38.1%), football (11.2%), and baseball (10.5%). Fracture site was significantly associated with patient sex, age, body mass index, laterality, mechanism, sport, time from injury, and presence of prodromal symptoms. The annual volume of pelvic avulsion fractures treated at the institution increased significantly from n=17 in 2005 to n=75 in 2019. CONCLUSIONS: Adolescent pelvic and hip avulsion fractures occur during a narrow window of age and skeletal maturation and are frequently sustained during sporting activities. Each fracture location is associated with certain demographic, mechanistic, and patient-specific characteristics. The associations between fracture site and patient-specific or injury-specific variables offer insights into the pathophysiology and possible underlying biomechanical risk factors that contribute to these injuries. LEVEL OF EVIDENCE: This is a level III retrospective study.

Do Osteochondroplasty Alone, Intertrochanteric Derotation Osteotomy, and Flexion-Derotation Osteotomy Improve Hip Flexion and Internal Rotation to Normal Range in Hips With Severe SCFE? - A 3D-CT Simulation Study.

BACKGROUND: Severe slipped capital femoral epiphysis (SCFE) leads to femoroacetabular impingement and restricted hip motion. We investigated the improvement of impingement-free flexion and internal rotation (IR) in 90 degrees of flexion following a simulated osteochondroplasty, a derotation osteotomy, and a combined flexion-derotation osteotomy in severe SCFE patients using 3D-CT-based collision detection software. METHODS: Preoperative pelvic CT of 18 untreated patients (21 hips) with severe SCFE (slip-angle>60 degrees) was used to generate patient-specific 3D models. The contralateral hips of the 15 patients with unilateral SCFE served as the control group. There were 14 male hips (mean age 13±2 y). No treatment was performed before CT. Specific collision detection software was used for the calculation of impingement-free flexion and IR in 90 degrees of flexion and simulation of osteochondroplasty, derotation osteotomy, and combined flexion-derotation osteotomy. RESULTS: Osteochondroplasty alone improved impingement-free motion but compared with the uninvolved contralateral control group, severe SCFE hips had persistently significantly decreased motion (mean flexion 59±32 degrees vs. 122±9 degrees, P <0.001; mean IR in 90 degrees of flexion -5±14 degrees vs. 36±11 degrees, P <0.001). Similarly, the impingement-free motion was improved after derotation osteotomy, and impingement-free flexion after a 30 degrees derotation was equivalent to the control group (113± 42 degrees vs. 122±9 degrees, P =0.052). However, even after the 30 degrees derotation, the impingement-free IR in 90 degrees of flexion persisted lower (13±15 degrees vs. 36±11 degrees, P <0.001). Following the simulation of flexion-derotation osteotomy, mean impingement-free flexion and IR in 90 degrees of flexion increased for combined correction of 20 degrees (20 degrees flexion and 20 degrees derotation) and 30 degrees (30 degrees flexion and 30 degrees derotation). Although mean flexion was equivalent to the control group for both (20 degrees and 30 degrees) combined correction, the mean IR in 90 degrees of flexion persisted decreased, even after the 30 degrees combined flexion-derotation (22±22 degrees vs. 36 degrees±11, P =0.009). CONCLUSIONS: Simulation of derotation-osteotomy (30 degrees correction) and flexion-derotation-osteotomy (20 degrees correction) normalized hip flexion for severe SCFE patients, but IR in 90 degrees of flexion persisted slightly lower despite significant improvement. Not all SCFE patients had improved hip motion with the performed simulations; therefore, some patients may need a higher degree of correction or combined treatment with osteotomy and cam-resection, although not directly investigated in this study. Patient-specific 3D-models could help individual preoperative planning for severe SCFE patients to normalize the hip motion. LEVEL OF EVIDENCE: III, case-control study.

Prediction of Late Dysplasia Based on Ultrasound and Plain X-Ray at 6 Months.

BACKGROUND: Developmental dysplasia of the hip represents a spectrum of deformity. Residual dysplasia at 2 years of age is associated with an increased risk for osteoarthritis and functional limitations. We compared the prognostic value of 6-month imaging modalities and aimed to identify optimal diagnostic metrics for the prediction of residual dysplasia. METHODS: After IRB approval, patients who underwent Pavlik treatment between 2009 and 2018 with 2-year follow-up were identified. Sonographs [ultrasound (US)] and radiographs (x-ray) were obtained at 6-month and 2-year-old visits. Dysplasia at 2 years was defined as an acetabular index (AI) >24 degrees. Receiver operating characteristic curves were constructed to quantitatively compare the prognostic ability of US and x-ray-based measures at 6 months. Youden's index [(YI) (values range from 0 (poor test) to 1 (perfect test)] was used to evaluate existing cutoffs at 6 months of age (normal measurements: alpha angle (AA) ≥60 degrees, femoral head coverage (FHC) ≥50%, and AI <30 degrees) relative to newly proposed limits. RESULTS: Fifty-nine patients were included, of which 28.8% of patients (95% CI: 17.3 to 40.4%) had acetabular dysplasia at 2 years. After adjusting for sex, AA [Area under the Curve (AUC): 80] and AI (AUC: 79) at 6 months of age were better tests than FHC (AUC: 0.77). Current diagnostic cutoffs for AA (YI: 0.08), AI (YI: 0.0), and FHC (YI: 0.06) at 6 months had poor ability to predict dysplasia at 2 years. A composite test of all measures based on proposed cutoffs (AA ≥73 degrees, FHC > 62% and AI ≤24 degrees) was a better predictor of dysplasia at 2 years (Youden's index (YI): 0.63) than any single metric. CONCLUSIONS: The rate of residual dysplasia remains concerning. The 6-month x-ray and US both play a role in the ongoing management of the developmental dysplasia of the hip. The prediction of dysplasia is maximized when all metrics are considered collectively. Existing parameters were not accurate; We recommend the following cutoffs: AA ≥73 degrees, FHC > 62%, and AI ≤24 degrees. These cutoffs must be validated. LEVEL OF EVIDENCE: Prognostic Level II.

Effects of joint loading on the development of capital femoral epiphysis morphology.

INTRODUCTION: The deleterious influence of increased mechanical forces on capital femoral epiphysis development is well established; however, the growth of the physis in the absence of such forces remains unclear. The hips of non-ambulatory cerebral palsy (CP) patients provide a weight-restricted (partial weightbearing) model which can elucidate the influence of decreased mechanical forces on the development of physis morphology, including features related to development of slipped capital femoral epiphysis (SCFE). Here we used 3D image analysis to compare the physis morphology of children with non-ambulatory CP, as a model for abnormal hip loading, with age-matched native hips. MATERIALS AND METHODS: CT images of 98 non-ambulatory CP hips (8-15 years) and 80 age-matched native control hips were used to measure height, width, and length of the tubercle, depth, width, and length of the metaphyseal fossa, and cupping height across different epiphyseal regions. The impact of age on morphology was assessed using Pearson correlations. Mixed linear model was used to compare the quantified morphological features between partial weightbearing hips and full weightbearing controls. RESULTS: In partial weightbearing hips, tubercle height and length along with fossa depth and length significantly decreased with age, while peripheral cupping height increased with age (r > 0.2, P < 0.04). Compared to normally loaded (full weightbearing) hips and across all age groups, partially weightbearing hips' epiphyseal tubercle height and length were smaller (P < .05), metaphyseal fossa depth was larger (P < .01), and posterior, inferior, and anterior peripheral cupping heights were smaller (P < .01). CONCLUSIONS: Smaller epiphyseal tubercle and peripheral cupping with greater metaphyseal fossa size in partial weightbearing hips suggests that the growing capital femoral epiphysis requires mechanical stimulus to adequately develop epiphyseal stabilizers. Deposit low prevalence and relevance of SCFE in CP, these findings highlight both the role of normal joint loading in proper physis development and how chronic abnormal loading may contribute to various pathomorphological changes of the proximal femur (i.e., capital femoral epiphysis).

Generalized Joint Laxity Is Associated With Dynamic Hip Ultrasonography Measures in Female Athlete Patients Who Are Not Hypermobile.

OBJECTIVES: To investigate ultrasound (US) femoroacetabular translation measurements in female athlete patients. METHODS: A prospective cross-sectional study was conducted in female athlete patients <50 years. Demographic data, Beighton score/hypermobility status, and sport participation were collected. Hip dysplasia was determined using radiographic measurements (lateral center edge angle, anterior center edge angle, Tönnis angle); femoral version angles were measured with CT or MR. Femoroacetabular translation US measures included neutral (N), neutral flexed (NF), extension external rotation/apprehension (EER) positions. Maximal difference (delta) between US measures was calculated. RESULTS: 206/349 female hips were analyzed (median age 21.2 years [range, 12-49.5]). The primary sport group was performing arts (45%, 92/206). Mean Beighton score was 5.2 (SD, 2.5) with 61% (129/206) of hips exhibiting hypermobility (Beighton score ≥5). For each additional unit of Beighton score, N US measurement increased by 0.7 mm (ß = 0.7; 95% confidence interval [CI] = 0.22-1.25; P < .001), NF by 1 mm ( ß = 0.9; 95% CI = 0.3-1.43; P = .002) and EER by 0.8 mm ( ß = 0.8; 95% CI = 0.27-1.37; P < .001) when adjusting for age and dysplasia status. A positive correlation was detected between NF (r = 0.19; 95% CI = 0.05-0.33; P = .007) and EER (r = 0.19; 95% CI = 0.05-0.32; P = .01) with Tönnis angle and a negative correlation between the delta and femoral version (r = -0.20; 95% CI = -0.35 to 0.03; P = .02). No difference in US measures was detected across sport groups (N [P = .24], NF [P = .51], EER [P = .20], delta [P = .07]). CONCLUSION: Beighton score was independently associated with dynamic US measures in female athlete patients who are not hypermobile when controlling for other factors.

Limited Hip Flexion and Internal Rotation Resulting From Early Hip Impingement Conflict on Anterior Metaphysis of Patients With Untreated Severe SCFE Using 3D Modelling.

INTRODUCTION: Slipped capital femoral epiphysis (SCFE) is the most common hip disorder in adolescent patients that can result in complex 3 dimensional (3D)-deformity and hip preservation surgery (eg, in situ pinning or proximal femoral osteotomy) is often performed. But there is little information about location of impingement.Purpose/Questions: The purpose of this study was to evaluate (1) impingement-free hip flexion and internal rotation (IR), (2) frequency of impingement in early flexion (30 to 60 degrees), and (3) location of acetabular and femoral impingement in IR in 90 degrees of flexion (IRF-90 degrees) and in maximal flexion for patients with untreated severe SCFE using preoperative 3D-computed tomography (CT) for impingement simulation. METHODS: A retrospective study involving 3D-CT scans of 18 patients (21 hips) with untreated severe SCFE (slip angle>60 degrees) was performed. Preoperative CT scans were used for bone segmentation of preoperative patient-specific 3D models. Three patients (15%) had bilateral SCFE. Mean age was 13±2 (10 to 16) years and 67% were male patients (86% unstable slip, 81% chronic slip). The contralateral hips of 15 patients with unilateral SCFE were evaluated (control group). Validated software was used for 3D impingement simulation (equidistant method). RESULTS: (1) Impingement-free flexion (46±32 degrees) and IRF-90 degrees (-17±18 degrees) were significantly ( P <0.001) decreased in untreated severe SCFE patients compared with contralateral side (122±9 and 36±11 degrees).(2) Frequency of impingement was significantly ( P <0.001) higher in 30 and 60 degrees flexion (48% and 71%) of patients with severe SCFE compared with control group (0%).(3) Acetabular impingement conflict was located anterior-superior (SCFE patients), mostly 12 o'clock (50%) in IRF-90 degrees (70% on 2 o'clock for maximal flexion). Femoral impingement was located on anterior-superior to anterior-inferior femoral metaphysis (between 2 and 6 o'clock, 40% on 3 o'clock and 40% on 5 o'clock) in IRF-90 degrees and on anterior metaphysis (40% on 3 o'clock) in maximal flexion and frequency was significantly ( P <0.001) different compared with control group. CONCLUSION: Severe SCFE patients have limited hip flexion and IR due to early hip impingement using patient-specific preoperative 3D models. Because of the large variety of hip motion, individual evaluation is recommended to plan the osseous correction for severe SCFE patients. LEVEL OF EVIDENCE: Level III.

Magnetization-prepared 2 Rapid Gradient-Echo MRI for B1 Insensitive 3D T1 Mapping of Hip Cartilage: An Experimental and Clinical Validation.

Background Often used for T1 mapping of hip cartilage, three-dimensional (3D) dual-flip-angle (DFA) techniques are highly sensitive to flip angle variations related to B1 inhomogeneities. The authors hypothesized that 3D magnetization-prepared 2 rapid gradient-echo (MP2RAGE) MRI would help provide more accurate T1 mapping of hip cartilage at 3.0 T than would 3D DFA techniques. Purpose To compare 3D MP2RAGE MRI with 3D DFA techniques using two-dimensional (2D) inversion recovery T1 mapping as a standard of reference for hip cartilage T1 mapping in phantoms, healthy volunteers, and participants with hip pain. Materials and Methods T1 mapping at 3.0 T was performed in phantoms and in healthy volunteers using 3D MP2RAGE MRI and 3D DFA techniques with B1 field mapping for flip angle correction. Participants with hip pain prospectively (July 2019-January 2020) underwent indirect MR arthrography (with intravenous administration of 0.2 mmol/kg of gadoterate meglumine), including 3D MP2RAGE MRI. A 2D inversion recovery-based sequence served as a T1 reference in phantoms and in participants with hip pain. In healthy volunteers, cartilage T1 was compared between 3D MP2RAGE MRI and 3D DFA techniques. Paired t tests and Bland-Altman analysis were performed. Results Eleven phantoms, 10 healthy volunteers (median age, 27 years; range, 26-30 years; five men), and 20 participants with hip pain (mean age, 34 years ± 10 [standard deviation]; 17 women) were evaluated. In phantoms, T1 bias from 2D inversion recovery was lower for 3D MP2RAGE MRI than for 3D DFA techniques (mean, 3 msec ± 11 vs 253 msec ± 85; P < .001), and, unlike 3D DFA techniques, the deviation found with MP2RAGE MRI did not correlate with increasing B1 deviation. In healthy volunteers, regional cartilage T1 difference (109 msec ± 163; P = .008) was observed only for the 3D DFA technique. In participants with hip pain, the mean T1 bias of 3D MP2RAGE MRI from 2D inversion recovery was -23 msec ± 31 (P < .001). Conclusion Compared with three-dimensional (3D) dual-flip-angle techniques, 3D magnetization-prepared 2 rapid gradient-echo MRI enabled more accurate T1 mapping of hip cartilage, was less affected by B1 inhomogeneities, and showed high accuracy against a T1 reference in participants with hip pain. © RSNA, 2021.

Does the Capital Femoral Physis Bony MorphologyDiffer in Children with Symptomatic Cam-type Femoroacetabular Impingement.

BACKGROUND: The epiphyseal tubercle, the corresponding metaphyseal fossa, and peripheral cupping are key stabilizers of the femoral head-neck junction. Abnormal development of these features in the setting of supraphysiologic physeal stress under high forces (for example, forces that occur during sports activity) may result in a cam morphology. Although most previous studies on cam-type femoroacetabular impingement (FAI) have mainly focused on overgrowth of the peripheral cupping, little is known about detailed morphologic changes of the epiphyseal and metaphyseal bony surfaces in patients with cam morphology. QUESTIONS/PURPOSES: (1) Does the CT-based bony morphology of the peripheral epiphyseal cupping differ between patients with a cam-type morphology and asymptomatic controls (individuals who did not have hip pain)? (2) Does the CT-based bony morphology of the epiphyseal tubercle differ between patients with a cam-type morphology and asymptomatic controls? (3) Does the CT-based bony morphology of the metaphyseal fossa differ between patients with a cam-type morphology and asymptomatic controls? METHODS: After obtaining institutional review board approval for this study, we retrospectively searched our institutional database for patients aged 8 to 15 years with a diagnosis of an idiopathic cam morphology who underwent a preoperative CT evaluation of the affected hip between 2005 and 2018 (n = 152). We excluded 96 patients with unavailable CT scans and 40 patients with prior joint diseases other than cam-type FAI. Our search resulted in 16 patients, including nine males. Six of 16 patients had a diagnosis of bilateral FAI, for whom we randomly selected one side for the analysis. Three-dimensional (3-D) models of the proximal femur were generated to quantify the size of the peripheral cupping (peripheral growth of the epiphysis around the metaphysis), epiphyseal tubercle (a beak-like prominence in the posterosuperior aspect of the epiphysis), and metaphyseal fossa (a groove on the metaphyseal surface corresponding to the epiphyseal tubercle). A general linear model was used to compare the quantified anatomic features between the FAI cohort and 80 asymptomatic hips (aged 8 to 15 years; 50% male) after adjusting for age and sex. A secondary analysis using the Wilcoxon matched-pairs signed rank test was performed to assess side-to-side differences in quantified morphological features in 10 patients with unilateral FAI. RESULTS: After adjusting for age and sex, we found that patients with FAI had larger peripheral cupping in the anterior, posterior, superior, and inferior regions than control patients who did not have hip symptoms or radiographic signs of FAI (by 1.3- to 1.7-fold; p < 0.01 for all comparisons). The epiphyseal tubercle height and length were smaller in patients with FAI than in controls (by 0.3- to 0.6-fold; p < 0.02 for all comparisons). There was no difference in tubercle width between the groups. Metaphyseal fossa depth, width, and length were larger in patients with FAI than in controls (by 1.8- to 2.3-fold; p < 0.001 for all comparisons). For patients with unilateral FAI, we saw similar peripheral cupping but smaller epiphyseal tubercle (height and length) along with larger metaphyseal fossa (depth) in the FAI side compared with the uninvolved contralateral side. CONCLUSION: Consistent with prior studies, we observed more peripheral cupping in patients with cam-type FAI than control patients without hip symptoms or radiographic signs of FAI. Interestingly, the epiphyseal tubercle height and length were smaller and the metaphyseal fossa was larger in hips with cam-type FAI, suggesting varying inner bone surface morphology of the growth plate. The docking mechanism between the epiphyseal tubercle and the metaphyseal fossa is important for epiphyseal stability, particularly at early ages when the peripheral cupping is not fully developed. An underdeveloped tubercle and a large fossa could be associated with a reduction in stability, while excessive peripheral cupping growth would be a factor related to improved physeal stability. This is further supported by observed side-to-side differences in tubercle and fossa morphology in patients with unilateral FAI. Further longitudinal studies would be worthwhile to study the causality and compensatory mechanisms related to epiphyseal and metaphyseal bony morphology in pathogenesis cam-type FAI. Such information will lay the foundation for developing imaging biomarkers to predict the risk of FAI or to monitor its progress, which are critical in clinical care planning. LEVEL OF EVIDENCE: Level III, prognostic study.

How Common Is Femoral Retroversion and How Is it Affected by Different Measurement Methods in Unilateral Slipped Capital Femoral Epiphysis?

BACKGROUND: Although femoral retroversion has been linked to the onset of slipped capital femoral epiphysis (SCFE), and may result from a rotation of the femoral epiphysis around the epiphyseal tubercle leading to femoral retroversion, femoral version has rarely been described in patients with SCFE. Furthermore, the prevalence of actual femoral retroversion and the effect of different measurement methods on femoral version angles has yet to be studied in SCFE. QUESTIONS/PURPOSES: (1) Do femoral version and the prevalence of femoral retroversion differ between hips with SCFE and the asymptomatic contralateral side? (2) How do the mean femoral version angles and the prevalence of femoral retroversion change depending on the measurement method used? (3) What is the interobserver reliability and intraobserver reproducibility of these measurement methods? METHODS: For this retrospective, controlled, single-center study, we reviewed our institutional database for patients who were treated for unilateral SCFE and who had undergone a pelvic CT scan. During the period in question, the general indication for obtaining a CT scan was to define the surgical strategy based on the assessment of deformity severity in patients with newly diagnosed SCFE or with previous in situ fixation. After applying prespecified inclusion and exclusion criteria, we included 79 patients. The mean age was 15 ± 4 years, 48% (38 of 79) of the patients were male, and 56% (44 of 79) were obese (defined as a BMI > 95th percentile (mean BMI 34 ± 9 kg/m2). One radiology resident (6 years of experience) measured femoral version of the entire study group using five different methods. Femoral neck version was measured as the orientation of the femoral neck. Further measurement methods included the femoral head's center and differed regarding the level of landmarks for the proximal femoral reference axis. From proximal to distal, this included the most-proximal methods (Lee et al. and Reikerås et al.) and most-distal methods (Tomczak et al. and Murphy et al.). Most proximally (Lee et al. method), we used the most cephalic junction of the greater trochanter as the landmark and, most distally, we used the center base of the femoral neck superior to the lesser trochanter (Murphy et al.). The orientation of the distal femoral condyles served as the distal reference axis for all five measurement methods. All five methods were compared side-by-side (involved versus uninvolved hip), and comparisons among all five methods were performed using paired t-tests. The prevalence of femoral retroversion (< 0°) was compared using a chi-square test. A subset of patients was measured twice by the first observer and by a second orthopaedic resident (2 years of experience) to assess intraobserver reproducibility and interobserver reliability; for this assessment, we used intraclass correlation coefficients. RESULTS: The mean femoral neck version was lower in hips with SCFE than in the contralateral side (-2° ± 13° versus 7° ± 11°; p < 0.001). This yielded a mean side-by side difference of -8° ± 11° (95% CI -11° to -6°; p < 0.001) and a higher prevalence of femoral retroversion in hips with SCFE (58% [95% CI 47% to 69%]; p < 0.001) than on the contralateral side (29% [95% CI 19% to 39%]). These differences between hips with SCFE and the contralateral side were higher and ranged from -17° ± 11° (95% CI -20° to -15°; p < 0.001) based on the method of Tomczak et al. to -22° ± 13° (95% CI -25° to -19°; p < 0.001) according to the method of Murphy et al. The mean overall femoral version angles increased for hips with SCFE using more-distal landmarks compared with more-proximal landmarks. The prevalence of femoral retroversion was higher in hips with SCFE for the proximal methods of Lee et al. and Reikerås et al. (91% [95% CI 85% to 97%] and 84% [95% CI 76% to 92%], respectively) than for the distal measurement methods of Tomczak et al. and Murphy et al. (47% [95% CI 36% to 58%] and 60% [95% CI 49% to 71%], respectively [all p < 0.001]). We detected mean differences ranging from -19° to 4° (all p < 0.005) for 8 of 10 pairwise comparisons in hips with SCFE. Among these, the greatest differences were between the most-proximal methods and the more-distal methods, with a mean difference of -19° ± 7° (95% CI -21° to -18°; p < 0.001), comparing the methods of Lee et al. and Tomczak et al. In hips with SCFE, we found excellent agreement (intraclass correlation coefficient [ICC] > 0.80) for intraobserver reproducibility (reader 1, ICC 0.93 to 0.96) and interobserver reliability (ICC 0.95 to 0.98) for all five measurement methods. Analogously, we found excellent agreement (ICC > 0.80) for intraobserver reproducibility (reader 1, range 0.91 to 0.96) and interobserver reliability (range 0.89 to 0.98) for all five measurement methods in healthy contralateral hips. CONCLUSION: We showed that femoral neck version is asymmetrically decreased in unilateral SCFE, and that differences increase when including the femoral head's center. Thus, to assess the full extent of an SCFE deformity, femoral version measurements should consider the position of the displaced epiphysis. The prevalence of femoral retroversion was high in patients with SCFE and increased when using proximal anatomic landmarks. Since the range of femoral version angles was wide, femoral version cannot be predicted in a given hip and must be assessed individually. Based on these findings, we believe it is worthwhile to add evaluation of femoral version to the diagnostic workup of children with SCFE. Doing so may better inform surgeons as they contemplate when to use isolated offset correction or to perform an additional femoral osteotomy for SCFE correction based on the severity of the slip and the rotational deformity. To facilitate communication among physicians and for the design of future studies, we recommend consistently reporting the applied measurement technique. LEVEL OF EVIDENCE: Level III, prognostic study.

What Is the Association Among Epiphyseal Rotation, Translation, and the Morphology of the Epiphysis and Metaphysis in Slipped Capital Femoral Epiphysis?

BACKGROUND: Contemporary studies have described the rotational mechanism in patients with slipped capital femoral epiphysis (SCFE). However, there have been limited patient imaging data and information to quantify the rotation. Determining whether the epiphysis is rotated or translated and measuring the epiphyseal displacement in all planes may facilitate planning for surgical reorientation of the epiphysis. QUESTIONS/PURPOSES: (1) How does epiphyseal rotation and translation differ among mild, moderate, and severe SCFE? (2) Is there a correlation between epiphyseal rotation and posterior or inferior translation in hips with SCFE? (3) Does epiphyseal rotation correlate with the size of the epiphyseal tubercle or the metaphyseal fossa or with epiphyseal cupping? METHODS: We identified 51 patients (55% boys [28 of 51]; mean age 13 ± 2 years) with stable SCFE who underwent preoperative CT of the pelvis before definitive treatment. Stable SCFE was selected because unstable SCFE would not allow for accurate assessment of rotation given the complete displacement of the femoral head in relation to the neck. The epiphysis and metaphysis were segmented and reconstructed in three-dimensions (3-D) for analysis in this retrospective study. One observer (a second-year orthopaedic resident) performed the image segmentation and measurements of epiphyseal rotation and translation relative to the metaphysis, epiphyseal tubercle, metaphyseal fossa, and the epiphysis extension onto the metaphysis defined as epiphyseal cupping. To assess the reliability of the measurements, a randomly selected subset of 15 hips was remeasured by the primary examiner and by the two experienced examiners independently. We used ANOVA to calculate the intraclass and interclass correlation coefficients (ICCs) for intraobserver and interobserver reliability of rotational and translational measurements. The ICC values for rotation were 0.91 (intraobserver) and 0.87 (interobserver) and the ICC values for translation were 0.92 (intraobserver) and 0.87 (intraobserver). After adjusting for age and sex, we compared the degree of rotation and translation among mild, moderate, and severe SCFE. Pearson correlation analysis was used to assess the associations between rotation and translation and between rotation and tubercle, fossa, and cupping measurements. RESULTS: Hips with severe SCFE had greater epiphyseal rotation than hips with mild SCFE (adjusted mean difference 21° [95% CI 11° to 31°]; p < 0.001) and hips with moderate SCFE (adjusted mean difference 13° [95% CI 3° to 23°]; p = 0.007). Epiphyseal rotation was positively correlated with posterior translation (r = 0.33 [95% CI 0.06 to 0.55]; p = 0.02) but not with inferior translation (r = 0.16 [95% CI -0.12 to 0.41]; p = 0.27). There was a positive correlation between rotation and metaphyseal fossa depth (r = 0.35 [95% CI 0.08 to 0.57]; p = 0.01), width (r = 0.41 [95% CI 0.15 to 0.61]; p = 0.003), and length (r = 0.56 [95% CI 0.38 to 0.75]; p < 0.001). CONCLUSION: This study supports a rotational mechanism for the pathogenesis of SCFE. Increased rotation is associated with more severe slips, posterior epiphyseal translation, and enlargement of the metaphyseal fossa. The rotational nature of the deformity, with the center of rotation at the epiphyseal tubercle, should be considered when planning in situ fixation and realignment surgery. Avoiding placing a screw through the epiphyseal tubercle-the pivot point of rotation- may increase the stability of the epiphysis. The realignment of the epiphysis through rotation rather than simple translation is recommended during the open subcapital realignment procedure. Enlargement of the metaphyseal fossa disrupts the interlocking mechanism with the tubercle and increases epiphyseal instability. Even in the setting of a stable SCFE, an increased fossa enlargement may indicate using two screws instead of one screw, given the severity of epiphyseal rotation and the risk of instability. Further biomechanical studies should investigate the number and position of in situ fixation screws in relation to the epiphyseal tubercle and metaphyseal fossa. LEVEL OF EVIDENCE: Level III, prognostic study.

Treatment Options for End-Stage Hip Disease in Adolescents: To Replace, Fuse, or Reconstruct?

INTRODUCTION: This paper aims to review the indications criteria for the surgical treatment of adolescents with hip osteoarthritis and summarize the contemporary techniques that orthopaedic surgeons can apply for hip reconstruction. DISCUSSION: Hip osteoarthritis remains a concerning burden to North American society. While the rate of total hip replacement (THR) in younger patients has increased in the last decades, younger patients may have a higher risk of revision hip replacement because of their increased level of activity and expected patient longevity compared with the elderly. Increased demand for multiple revision surgeries is a concern for the adolescent patient. Although in general THR has been increasingly recommended for the treatment of end-stage osteoarthritis secondary to pediatric hip disorders, hip arthrodesis remains a beneficial alternative for the treatment of severe hip disease secondary to infection and for patients who desire to engage in a very active lifestyle. Hip preservation procedures are ideally performed in the prearthritic stage or in hips with minimal degeneration to preserve the joint and achieve the most optimal outcomes. However, adolescents and young adults with moderate and rarely advanced arthritis may benefit from surgical treatment using hip preservation techniques. CONCLUSIONS: Treatment of adolescents with pain and dysfunction because of end-stage hip disease is challenging and controversial. THR and arthrodesis are the 2 principal alternatives. However, in particular circumstances, hip reconstruction may be recommended.

The Effect of Modality and Landmark Selection on MRI and CT Femoral Torsion Angles.

Background Assessment of femoral torsion at preoperative hip imaging is commonly recommended. However, it is unclear whether MRI is as accurate as CT and how different methods affect femoral torsion measurements. Purpose To compare MRI- and CT-based assessment of femoral torsion by using four commonly used measurement methods in terms of agreement, reproducibility, and reliability and to compare femoral torsion angles between the four different measurement methods. Materials and Methods This retrospective study evaluated patients with hip pain who underwent CT and 3-T MRI of the hip including sequences of the pelvis and distal condyles between May 2017 and June 2018. The four measurement methods differed regarding the landmark levels for the proximal femoral reference axis and included measurements at the level of the greater trochanter, femoral neck, base of the femoral neck, and level of the lesser trochanter. Intraclass correlation coefficients (ICCs) were calculated, and Bland-Altman analysis was performed. Results Forty-five patients (mean age ± standard deviation, 19 years ± 5; 27 female) and 57 hips were evaluated. Inter- and intrarater reliability were excellent for each of the four CT- and MRI-based measurement methods (ICC range, 0.97-0.99). Mean difference between CT- and MRI-based measurement ranged from 0.3° ± 3.4 (P = .58) to 2.1° ± 4.1 (P < .001). Differences between CT and MRI were within the corresponding ICC variation for all four measurement methods. Mean torsion angles were greater by 17.6° for CT and 18.7° for MRI (all P < .001) between the most proximal to the most distal measurement methods. Conclusion MRI- and CT-based femoral torsion measurements showed high agreement and comparable reliability and reproducibility but were dependent on the level of selected landmarks used to define the proximal reference axis. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Zoga in this issue.

What Proportion of Patients Undergoing Bernese Periacetabular Osteotomy Experience Nonunion, and What Factors are Associated with Nonunion?

BACKGROUND: The Bernese periacetabular osteotomy (PAO) is one of the most-used surgical techniques to treat symptomatic acetabular dysplasia. Although good functional and radiographic short-term and long-term outcomes have been reported, several complications after PAO have been described. One complication that may compromise clinical results is nonunion of an osteotomy. However, the exact prevalence and risk factors associated with nonunion are poorly elucidated. QUESTIONS/PURPOSES: (1) What proportion of patients have complete bony healing versus nonunion during the first year after PAO? (2) What is the clinical and functional impact of nonunion at a minimum of 1 year after PAO, as assessed by the modified Harris hip score (mHHS) and the Hip Disability and Osteoarthritis Outcome Score (HOOS)? (3) What patient-specific or surgery-specific factors are associated with nonunion at 6 months and at a minimum of 1 year postoperatively? METHODS: Between January 2012 and December 2015, we retrospectively identified 314 patients who underwent PAO at our institution. During this period, 28 patients with a diagnosis different from symptomatic acetabular dysplasia (reverse PAO for acetabular over-coverage: n = 25; PAO for skeletal chondrodysplasia: n = 3) underwent PAO but were ineligible to participate. Hence, 286 patients underwent PAO to treat symptomatic acetabular dysplasia during the study period and were considered eligible. Inclusion criteria were patients with a complete set of postoperative radiographs (AP, Dunn lateral, and false-profile) at 12 months or more postoperatively. Eighteen percent (51 of 286) of the patients underwent staged, bilateral PAOs, but we only included the first PAO. Finally, 14% (41 of 286) of the patients were excluded because they had an incomplete set of postoperative radiographs at 12 months or more. The study comprised 245 patients. Eighty-five percent (209 of 245) of the patients were female and the mean age at surgery was 24 years ± 9 years. The healing status (complete healing vs. nonunion) was recorded for ischial, superior pubic, supraacetabular, and posterior column osteotomies at each subsequent visit. Nonunion was defined as noncontiguous osseous union with a persistent radiolucent line across any osteotomy site and was recorded at 3 months, approximately 6 months, and approximately 12 months postoperatively. Calculation of Cohen's kappa statistic coefficients showed the classification had perfect interobserver agreement (0.53; 95% confidence interval, 0.12-0.93), but there was moderate intraobserver agreement between those who healed and those with nonunion. The HOOS and mHHS were collected preoperatively and at a minimum of 1 year after PAO. The HOOS contains five separate subscales for pain, symptoms, activity of daily living, sport and recreational function, and hip-related quality of life. The HOOS responses are normalized on a scale of 0 (worst) to 100 (best). The mHHS includes pain and function scales and is overall interpreted on a scale from 0 (worst) to 100 (best). Eighty-six percent (211 of 245) of the patients with a complete set of images at their 12-month visit completed the mHHS and 89% (217 of 245) completed the HOOS. We collected information from the patients' medical records about their symptomatic status and additional treatment for nonunion. A logistic regression analysis was used to investigate factors associated with nonunion at 6 and 12 months postoperatively. RESULTS: Only 45% (96 of 215) of the patients had complete radiographic healing of all osteotomy sites at the 6-month visit and 55% (119 of 215) had not healed completely. However, 92% (225 of 245) demonstrated complete radiographic healing of all osteotomy sites at approximately 1 year postoperatively. The proportion of nonunion at a minimum of 12 months after PAO was 8% (20 of 245 patients). There was no difference in the mHHS after 1 year or more of follow-up between patients with nonunion and patients with complete healing after PAO (nonunion mean mHHS: 73; 95% CI, 62-85 versus healed: 82; 95% CI, 80-85; p = 0.13) and HOOS pain (nonunion mean HOOS pain: 80; 95% CI, 71-90 versus healed: 86; 95% CI, 83-88; p = 0.16). Similarly, no difference was identified for HOOS symptoms (nonunion mean: 72; 95% CI, 63-80 versus healed: 78; 95% CI, 75-81; p = 0.11), HOOS activities of daily living (nonunion mean: 86; 95% CI, 78-94 versus healed: 91; 95% CI, 89-93; p = 0.09), HOOS sports and recreation (nonunion mean: 70; 95% CI, 57-83 versus healed: 78; 95% CI, 75-82; p = 0.18); and HOOS quality of life (nonunion mean: 60; 95% CI, 46-75 versus healed: 69; 95% CI, 65-72; p = 0.28). After controlling for potentially confounding variables such as gender, age, chisel type, and preoperative anterior center-edge angle, we found that higher BMI (per 1 k/m; odds ratio 1.14; 95% CI, 1.06-1.22; p < 0.01), older age (per 1 year; OR 1.05; 95% CI, 1.01-1.08; p < 0.01) and more-severe acetabular dysplasia as assessed by a decreased preoperative lateral center-edge angle (per 1°; OR 1.06; 95% CI, 1.02-1.11; p < 0.01) were independently associated with nonunion of one or more osteotomy sites at 6 months postoperatively. Only age was an independent predictor of nonunion at 12 months postoperatively (per 1 year; OR 1.06; 95% CI, 1.01-1.11; p = 0.02). CONCLUSIONS: Our study helps us to understand radiographic healing during the first year after PAO to treat symptomatic acetabular dysplasia. Fewer than half of the patients had complete healing of their osteotomies at 6 months postoperatively. More than 90% of patients can expect to have completely healed osteotomy sites at 12 months postoperatively. Surgeons should avoid unnecessary interventions if nonunion is observed radiographically at 6 months postoperatively. Although there was no difference in the HOOS and mHHS between patients with nonunion and those with complete healing, further research with a larger cohort is needed to clarify the impact of nonunion on clinical and functional outcomes after PAO. Surgeons should consider using strategies to enhance osteotomy healing in those who undergo PAO, such as optimizing vitamin D levels and using local bone grafts in older patients, those with a high BMI, and patients with severe acetabular dysplasia. LEVEL OF EVIDENCE: Level III, therapeutic study.

What Is the Accuracy and Reliability of the Peritubercle Lucency Sign on Radiographs for Early Diagnosis of Slipped Capital Femoral Epiphysis Compared With MRI as the Gold Standard?

BACKGROUND: The diagnosis of slipped capital femoral epiphysis (SCFE) often is delayed. Although lack of clinical suspicion is the main cause of delayed diagnosis, typical radiographic changes may not be present during the initial phases of SCFE. The peritubercle lucency sign for follow-up of the contralateral hip in patients with unilateral SCFE may be beneficial in assisting the early diagnosis. However, the accuracy and reliability of this sign in patients with SCFE is unknown. QUESTIONS/PURPOSES: (1) What is the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the peritubercle lucency sign on radiographs for the early diagnosis of SCFE compared with MRI as the gold standard? (2) What are the interobserver and intraobserver reliabilities of the peritubercle lucency sign on radiographs? METHODS: Between 2000 and 2017, 71 patients underwent MRI for an evaluation of pre-slip or a minimally displaced SCFE. Sixty percent of hips (43 of 71) had confirmed SCFE or pre-slip based on the presence of hip pain and MRI changes, and these patients underwent in situ pinning. Three independent experienced observers reviewed MR images of the 71 hips and agreed on the presence of a juxtaphyseal bright-fluid signal suggesting bone marrow edema in these 43 hips with SCFE, and absence MRI changes in the remaining 28 hips. The same three experienced observers and two inexperienced observers, including a general radiologist and an orthopaedic surgery resident, blindly assessed the radiographs for the presence or absence of the peritubercle lucency sign, without information about the diagnosis. Diagnostic accuracy measures including sensitivity, specificity, PPV, and NPV were evaluated. Intraobserver and interobserver agreements were calculated using kappa statistics. RESULTS: The overall accuracy of the peritubercle lucency sign on radiographs was 94% (95% CI 91 to 96), sensitivity was 97% (95% CI 95 to 99), specificity was 89% (95% CI 90 to 96), PPV was 93% (95% CI 90 to 96), and NPV was 95% (95% CI 92 to 99). All accuracy parameters were greater than 85% for the five observers, regardless of experience level. Intraobserver agreement was perfect (kappa 1.0), and interobserver agreement was excellent for the peritubercle lucency sign on radiographs across the five observers (kappa 0.81 [95% CI 0.73 to 0.88]). The reliability was excellent for experienced observers (kappa 0.88 [95% CI 0.74 to 1.00]) and substantial for inexperienced observers (kappa 0.70 [95% CI 0.46 to 0.93]), although no difference was found with the numbers available (p = 0.18). CONCLUSIONS: The peritubercle lucency sign on radiographs is accurate and reliable for the early diagnosis of SCFE compared with MRI as the gold standard. Improving the early diagnosis of SCFE may be possible with increased awareness, high clinical suspicion, and a scrutinized evaluation of radiographs including an assessment of the peritubercle lucency sign. LEVEL OF EVIDENCE: Level III, diagnostic study.

What Is the Impact of Periacetabular Osteotomy Surgery on Patient Function and Activity Levels?

BACKGROUND: Periacetabular osteotomy (PAO) is a hip preserving procedure performed often in younger, highly active patients. However, counseling patients is difficult, as there are limited data regarding activity level after PAO. The purpose of this study is to analyze the physical activity levels after PAO in a large, prospective multicenter cohort. METHODS: Prospectively collected data from a multicenter study group included 359 hips treated by PAO for hip dysplasia at a mean age of 25.1 years. Patient demographics, radiographic measures, operative data, and clinical outcomes were evaluated preoperatively, at 1 year, and at minimum 2 years postoperatively. Activity level was assessed with the University of California Los Angeles (UCLA) activity score, and patients were stratified into low activity, moderate activity, and high activity groups based on preoperative function. RESULTS: Compared to preoperative scores across the complete cohort, postoperative UCLA scores were improved on average 0.6 points at final follow-up (P = .001). The low activity and moderate activity groups had significant improvement in UCLA scores (P < .001 and P = .0007, respectively), while the high activity groups saw a significant decrease in UCLA activity scores (P < .0001). Modified Harris Hip Score, Hip Disability and Osteoarthritis Score Pain, and Hip Disability and Osteoarthritis Score Sports and Recreation scores were significantly improved across all preoperative activity levels. Multivariable linear regression (r2 = 0.45) confirmed prior ipsilateral surgery as a predictor for change in UCLA score (P = .002). CONCLUSION: Overall, these data suggest that consistent improvements in activity level and function can be expected following PAO surgery, with greater gains experienced by patients with lower preoperative levels of activity.

Capital Femoral Epiphyseal Cupping and Extension May Be Protective in Slipped Capital Femoral Epiphysis: A Dual-center Matching Cohort Study.

BACKGROUND: Peripheral cupping of the capital femoral epiphysis over the metaphysis has been reported as a precursor of cam morphology, but may also confer stability of the epiphysis protecting it from slipped capital femoral epiphysis (SCFE). The purpose of this study was to investigate the relationship between a novel morphologic parameter of inherent physeal stability, epiphyseal cupping, and the development of SCFE in a dual-center matched-control cohort study. METHODS: We performed a dual-center age-matched and sex-matched cohort study comparing 279 subjects with unilateral SCFE and 279 radiographically normal controls from 2 tertiary children's hospitals. All SCFE patients had at least 18 months of radiographic follow-up for contralateral slip surveillance. Anteroposterior and frog lateral pelvis radiographs were utilized to measure the epiphyseal cupping ratio and the current standard measure of inherent physeal stability, the epiphyseal extension ratio. RESULTS: Control hips were found to have greater epiphyseal cupping than the contralateral uninvolved hip of SCFE subjects both superiorly (0.28±0.08 vs. 0.24±0.06; P<0.001) and anteriorly (0.22±0.07 vs. 0.19±0.06; P<0.001). The 58/279 (21%) subjects who went on to develop contralateral slip had decreased epiphyseal cupping superiorly (0.25±0.07 vs. 0.23±0.05; P=0.03) and anteriorly (0.20±0.06 vs. 0.17±0.04; P<0.001). When we compared controls with hips that did not progress to contralateral slip and hips that further developed a contralateral SCFE, 1-way ANOVA demonstrated a stepwise decrease in epiphyseal cupping and epiphyseal extension ratio in the anterior and superior planes from control hips to contralateral hips without subsequent slip to contralateral hips that developed a SCFE (P<0.01 for each). CONCLUSIONS: This study provides further evidence that epiphyseal cupping around the metaphysis is associated with decreased likelihood of SCFE and may reflect increased inherent physeal stability. Epiphyseal cupping may represent an adaptive mechanism to stabilize the epiphysis during adolescence at the long-term cost of the eventual development of associated cam-femoroacetabular impingement deformity. LEVELS OF EVIDENCE: Level III-prognostic Study.

Vascular Supply to the Femoral Head in Patients With Healed Slipped Capital Femoral Epiphysis.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) is one of the most common hip disorders. The vascularity of the lateral epiphyseal vessels supplying the femoral head in patients with healed SCFE has not been well defined. The purpose of this study was to characterize the location and number of lateral epiphyseal vessels in young adults with healed SCFE. METHODS: This was a retrospective study of 17 patients (18 hips) with a diagnosis of SCFE and a matched control group of 17 patients (17 hips) with developmental dysplasia of the hip. All patients underwent high-resolution contrast-enhanced magnetic resonance imaging to visualize the path of the medial femoral circumflex artery and the lateral epiphyseal arterial branches supplying the femoral head. RESULTS: There were 5 unstable SCFEs and 13 stable SCFEs with an average slip angle of 31 degrees. (All patients had been treated with in situ pinning and screw removal). Average age at time of magnetic resonance imaging was 24.5 years (range, 15 to 34 y). The lateral epiphyseal vessels reliably inserted on the posterior-superior aspect of the femoral neck from the superior-anterior to the superior-posterior position in both the SCFE and control groups. An average of 2 (±0.8) retinacular vessels were identified in the SCFE group compared with 5.2 (±0.7) retinacular vessels in the control group (P<0.001). CONCLUSIONS: In healed SCFE, the lateral epiphyseal vessels reliably insert in the same anatomic region as patients with hip dysplasia; however, the overall number of vessels is significantly lower.

A new dye based on anthocyanins from the acai fruit (Euterpe oleracea) for chromovitrectomy in humans: clinical trial results.

PURPOSE: To test the applicability of the acai dye at a 25% concentration for identifying the posterior hyaloids and internal limiting membranes (ILMs) during pars plana vitrectomy (PPV) in human eyes with macular holes (MHs). METHODS: This study included 25 patients with chronic idiopathic MHs. The exclusion criteria included glaucoma, previous significant ocular conditions, and previous ocular surgeries except uncomplicated cataract. Ten surgeons performed 23-gauge four-port PPV, phacoemulsification, posterior hyaloid detachment, ILM peeling guided by dye staining, and perfluoropropane injection. The patients remained prone for 5 days postoperatively. The patients were evaluated postoperatively after 1, 30, and 180 days. The surgeons completed a questionnaire regarding the dye's staining abilities. RESULTS: The posterior hyaloids and ILMs stained purple in all eyes. The final best-corrected visual acuity improved significantly (p < 0.001) from preoperatively (1.37 ± 0.29) to 180 days postoperatively (1.05 ± 0.43). The MHs closed in 76% of eyes. CONCLUSION: The acai dye at a 25% concentration identified posterior hyaloids and ILMs during PPVs in humans. Dye toxicity was unlikely.

INTRAVITREAL ZIV-AFLIBERCEPT FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results.

PURPOSE: To evaluate the 52-week safety and efficacy of intravitreal ziv-aflibercept in patients with neovascular age-related macular degeneration. METHODS: All patients received three monthly intravitreal injections of 0.05 mL of ziv-aflibercept (1.25 mg) followed by a pro re nata regimen. The best-corrected visual acuity and spectral domain optical coherence tomography were obtained at baseline and monthly. Full-field and multifocal electroretinograms were obtained at baseline and 4, 13, 26, and 52 weeks. For some full-field electroretinography parameters, we calculated the differences between baseline and 52 weeks and then compared those differences between treated and untreated fellow eyes. RESULTS: Fifteen patients were included and 14 completed the 52-week follow-up. The mean best-corrected visual acuity improved from 0.95 ± 0.41 (20/200) at baseline to 0.75 ± 0.51 (20/125) logarithm of the minimum angle of resolution at 52 weeks (P = 0.0066). The baseline central retinal thickness decreased from 478.21 ± 153.48 µm to 304.43 ± 98.59 µm (P = 0.0004) at 52 weeks. Full-field electroretinography parameters used to assess retinal toxicity after intravitreal injections (rod response and oscillatory potentials) remained unchanged during follow-up. The average multifocal electroretinography macular response in 5° showed increased N1-P1 amplitude and decreased P1 implicit time (P < 0.05). One patient presented with intraocular inflammation after the seventh intravitreal procedure. CONCLUSION: The results suggested that intravitreal ziv-aflibercept might be safe and effective for treating neovascular age-related macular degeneration. More patients and a longer follow-up are needed to confirm the long-term outcomes of intravitreal ziv-aflibercept.