How is eyeball growth associated with optic nerve head shape and glaucoma? The Lamina cribrosa/Bruch's membrane opening offset theory.

The optic nerve head (ONH) is a complex structure wherein the axons of the retinal ganglion cells extrude from the eyeball through three openings: 1) the Bruch's membrane opening (BMO) in the retinal layer, 2) the anterior scleral canal opening in the anterior scleral layer, and 3) the lamina cribrosa (LC). Eyeball expansion during growth induces an offset among openings, since the expansion affects the inner retinal and outer scleral layers differently: the posterior polar retinal structure is preserved by the preferential growth in the equatorial region, whereas no such regional difference is observed in the scleral layer. The various modes and extents of eyeball expansion result in diverse directionality and amount of offset among openings, which causes diverse ONH morphology in adults, especially in myopia. In this review, we summarize the ONH changes that occur during myopic axial elongation. These changes were observed prospectively in our previous studies, wherein LC shift and subsequent offset from the BMO center could be predicted by tracing the central retinal vascular trunk position. This offset induces the formation of γ-zone parapapillary atrophy or externally oblique border tissue. As a presumptive site of glaucomatous damage, the LC/BMO offset may render the LC pores in the opposite direction more vulnerable. To support such speculation, we also summarize the relationship between LC/BMO offset and glaucomatous damage. Indeed, LC/BMO offset is not only the cause of diverse ONH morphology in adults, but is also, potentially, an important clinical marker for assessment of glaucoma.

Optic nerve head factors associated with initial central visual field defect in primary open-angle glaucoma.

We investigated optic nerve head factors associated with initial parafoveal scotoma (IPFS) in primary open-angle glaucoma. Eighty (80) patients with an IPFS and 84 patients with an initial nasal step (INS) were compared. Central retinal vascular trunk (CRVT) deviation from the Bruch's membrane opening (BMO) center was measured as a surrogate of lamina cribrosa (LC)/BMO offset, and its obliqueness was defined as the absolute value of angular deviation from the fovea-BMO axis. Proximity of retinal nerve fiber layer defect (RNFLD) was defined as the angular deviation of the inner RNFLD margin from the fovea-BMO axis. Microvasculature dropout (MvD) was defined as a focal sectoral capillary dropout with no visible microvascular network identified in the choroidal layer. Factors associated with IPFS, as compared with INS, were assessed using logistic regression analyses and conditional inference tree analysis. The IPFS group had more oblique CRVT offset (P < 0.001), RNFLD closer to the fovea (P < 0.001), more MvD (P < 0.001), and more LC defects (P < 0.001) compared to the INS group. In logistic regression analyses, obliqueness of CRVT offset (P = 0.002), RNFLD proximity (P < 0.001), and MvD (P = 0.001) were significant factors influencing the presence of IPFS. Conditional inference tree analysis showed that RNFLD closer to the fovea (P < 0.001) in the upper level, more oblique CRVT offset (P = 0.013) and presence of MvD (P = 0.001) in the lower level were associated with the probability of having IPFS. IPFS was associated with closer RNFLD location to the fovea when assessed from the BMO. Oblique LC/BMO offset may not only mask RNFLD proximity to the fovea due to a deviated funduscopic disc appearance, but also potentiate IPFS via focal LC defect and MvD.

Comparison of current relative value unit-based prices and utility between common surgical procedures, including orthopedic surgeries, in South Korea.

BACKGROUND: The medical pricing system strongly influences physicians' job satisfaction and patient health outcomes. This study aimed to investigate the current relative value unit (RVU)-based pricing and utility of patients in commonly performed surgical procedures in South Korea. METHODS: Fifteen common surgical procedures were selected from OECD statistics, and three additional orthopedic procedures were examined. The current pricing of each surgical procedure was retrieved from the Korea National Health Insurance Service, and the corresponding utilities were obtained as quality-adjusted life year (QALY) gains from previous studies. The relationship between the current prices (RVUs) and the patients' utility (incremental QALY gains/year) was analyzed. Subgroup analysis was performed between fatal and non-fatal procedures and between orthopedic and non-orthopedic procedures. RESULTS: A significant negative correlation (r = - 0.558, p < 0.001) was observed between RVU and incremental QALY among all 18 procedures. The fatal subgroup had a significantly higher RVU than the non-fatal subgroup (p < 0.05), while the former had a significantly lower incremental QALY than the latter (p < 0.001). Orthopedic procedures showed higher incremental QALY values than non-orthopedic procedures, but they did not show higher prices (RVU). CONCLUSIONS: This paradoxical relationship between current prices and patient utility is attributed to the higher pricing of surgical procedures for fatal and urgent conditions. Orthopedic surgery has been found to be a cost-effective treatment strategy. These findings could contribute to a better understanding of the potential role of incremental QALY in pursuing value-based purchasing or reasonable modification of the current medical fee schedule.

Association between eyeball asymmetry and offset of openings in optic nerve head canal assessed by posterior polar eyeball topography.

We investigated three-dimensional (3D) eyeball protrusion and its association with the offset between the lamina cribrosa (LC) and Bruch's membrane opening (BMO). 3D-MRI scans were taken from 93 subjects (186 eyes). An ellipsoid was fitted along the posterior 2/3 contour of each eyeball. Eyeball asymmetry with focal bulging was determined by the existence of an adjacent outward protrusion/reciprocal inward depression pair, and the angular deviation of the outermost protruded point (OPP) was measured from the nasal side of the fovea-BMO axis. The LC/BMO offset was evaluated by measuring the central retinal vascular trunk (CRVT) location from the BMO center: (1) the angular deviation and (2) the offset index as the ratio between the CRVT-BMO center distance and the BMO radius in the same direction. Seventy-nine eyes (42%) were classified as having eyeball asymmetry, which had a more superior LC/BMO offset (P < 0.001) and a larger offset index (P = 0.002). In those eyes, the angular deviation of the OPP showed a significant correlation with that of the LC/BMO offset (r = -0.724, P < 0.001), as did protrusion depth with the offset index (r = 0.291, P = 0.009). The presence of eyeball asymmetry was associated with superior LC/BMO offset (P = 0.004) and larger offset index (P = 0.009). Superior LC/BMO offset was associated with older age (P < 0.001), shorter axial length (P < 0.001) and inferior location of OPP (P < 0.001). The location and extent of focal bulging were closely associated with those of LC/BMO offset. This indicates that focal bulging during expansion might be associated with diverse directionality of LC/BMO offset.

Prolonged Union in Conservative Treatment of Symphalangeal Toe Fractures: Case Series.

Background: Toe symphalangism is characterized by a fusion of the interphalangeal joint between the middle and distal phalanges. While typical lesser toe fractures heal well with conservative treatment, in our clinical experience, we encountered patients with symphalangeal toe fractures who experienced long-lasting pain and delayed radiographic union. Therefore, this study aimed to report radiographic outcomes following conservative treatment of symphalangeal fractures of the lesser toes. Methods: We retrospectively reviewed 14 patients with symphalangeal lesser toe fractures who were treated conservatively. We investigated the mechanism of injury and measured the time from the initial injury date to the complete radiographic union. The fracture gap distance was measured on an initial lateral radiograph. Results: Symphalangeal fractures involved the fourth toe in 4 patients (28.5%) and the fifth toe in 10 patients (71.4%). Regarding the mechanism of injury, 6 patients (42.9%) were injured by stubbing or bumping into the door, 5 patients (35.7%) were injured by tripping, 2 patients (14.3%) were injured by heavy objects falling directly on their toes, and 1 patient (2.3%) complained of pain after wearing pointed shoes for half a day. The mean time to complete union was 9.1 months, and the median period was 5.5 months (range, 0.8-29 months). The initial gap of the fracture was 0.60 mm (range, 0.30-1.04 mm). Conclusions: The results of our case series may help counsel patients in the outpatient clinic that prolonged healing time may be required for the union of symphalangeal toe fractures.

Postoperative Stability in Displaced Ankle Fractures With Concomitant Ligamentous Injuries.

Ankle instability, which can be attributed to either the deltoid or lateral ligamentous complex, may be both a cause and a consequence of ankle fractures. This study aimed to assess postoperative ankle instability in patients with displaced ankle fractures. A total of 54 patients with displaced ankle fractures were included. Malleolar fractures were surgically reduced and fixated, and if necessary, the syndesmosis was stabilized. Concomitant deltoid injuries were left unrepaired. Ankle stress radiographs were taken approximately 25.4 months after surgery, with a standard deviation of 20.5 months. Radiographic measurements included the tibiotalar tilt angle (TT) on varus stress view, anterior translation of the talus (AT) on the anterior drawer view, and the medial clear space (MC) and tibiotalar tilt angle on the valgus stress view. These measurements were compared between the injured and the noninjured contralateral ankle for all patients as well as in a subgroup of 19 patients with concomitant deltoid and syndesmosis injuries. There were no significant differences in Varus TT (p = .675, p = .394), AT (p = .516, p = .967), Valgus MC (p = .190, p = 0.498), and Valgus TT (p = .173, p = .442) between the injured and noninjured ankles in the whole group of patients as well as in the subgroup of patients with concomitant deltoid and syndesmosis injuries. Patients with displaced ankle fractures exhibited radiographically stable ankles postoperatively. Syndesmosis fixation without deltoid ligament repair is a viable treatment option for achieving ankle stability postoperatively in fractures with both ligament injuries.

Radiographic Evaluation of the Association between Foot Deformities and Ankle Medial Osteoarthritis.

Background: Foot deformities can cause abnormal biomechanics of the ankle joint and the development of osteoarthritis. It was hypothesized that foot deformities would be related to medial ankle osteoarthritis, and this study investigated this relationship using radiographic measurements. Methods: Seventy-six ankles of 76 patients (32 men and 44 women; mean age, 69.0 years) with medial ankle osteoarthritis were included. Eleven radiographic measurements evaluated ankle joint orientation (tibial plafond inclination [TPI], medial distal tibial angle [MDTA], and anterior distal tibial angle [ADTA]), ankle joint incongruency (tibiotalar tilt [TT]), foot deformities (lateral talo-first metatarsal angle [Lat talo-1MT], anteroposterior talo-first metatarsal angle [AP talo-1MT], and talonavicular coverage), talar body migration (medial talar center migration [MTCM] and anterior talar center migration [ATCM]), internal rotation (IR) of the talus, and mechanical tibiofemoral angle. All were statistically analyzed using Pearson's correlation coefficients and regression analyses. Results: Ankle joint orientation to the ground (TPI, p = 0.002), increased foot arch (Lat talo-1MT, p < 0.001), and IR of the talus (p = 0.001) were significantly associated with ankle joint incongruency (TT) in linear regression analysis. Ankle joint incongruency (TT, p = 0.003), medial talar body migration (MTCM, p = 0.042), and increased foot arch (Lat talo-1MT, p = 0.022) were significantly associated with IR of the talus in the binary logistic regression analysis. MTCM was significantly correlated with TPI (r = 0.251, p = 0.029), TT (r = 0.269, p = 0.019), MDTA (r = 0.359, p = 0.001), ATCM (r = -0.522, p < 0.001), and AP talo-1MT (r = 0.296, p = 0.015). ATCM was significantly correlated with TPI (r = -0.253, p = 0.027), ADTA (r = 0.349, p = 0.002), and Lat talo-1MT (r = -0.344, p = 0.002). Conclusions: Ankle joint orientation, foot deformities, and talar rotation were associated with ankle joint incongruency in medial ankle osteoarthritis when evaluated radiographically. These findings need to be considered during surgical treatment for medial ankle osteoarthritis. However, the biomechanical significance of these radiographic measurements requires further investigation.

Dynamic Foot Pressure During Walking: A Potential Indicator of Bone Mineral Density.

BACKGROUND: Physical skeletal loading can affect the bone mineral density (BMD). This study investigated the association between BMD and dynamic foot pressure during gait. METHODS: A total of 104 patients (mean age, 62.6 ± 12.4 years; 23 male and 81 female) who underwent dual x-ray absorptiometry and pedobarography were included. BMD values of the lumbar spine, femoral neck, and total femur were assessed. The mean and maximum pressures were measured at the hallux, lesser toes, 1st metatarsal head, 2nd and 3rd metatarsal heads, 4th and 5th metatarsal heads, midfoot, medial heel, and lateral heel. Multivariable regression analysis was performed to identify factors significantly associated with BMD. RESULTS: The lumbar spine BMD was significantly associated with the mean pressure at the 4th and 5th metatarsal heads (p = 0.041, adjusted R 2 of model = 0.081). The femoral neck BMD was significantly associated with the maximum pressure at the 2nd and 3rd metatarsal heads (p = 0.002, adjusted R 2 = 0.213). The total femoral BMD also showed a significant association with the maximum pressure at the 2nd and 3rd metatarsal heads (p = 0.003, adjusted R 2 = 0.360). CONCLUSIONS: Foot plantar pressure during gait was significantly associated with BMD, and could potentially be used to predict the presence of osteoporosis. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Predisposal of Interferon Regulatory Factor 1 Deficiency to Accumulate DNA Damage and Promote Osteoarthritis Development in Cartilage.

OBJECTIVE: Interferon regulatory factor 1 (IRF1) is a transcriptional regulator conventionally associated with immunomodulation. Recent molecular analyses mapping DNA binding sites of IRF1 have suggested its potential function in DNA repair. However, the physiologic significance of this noncanonical function remains unexplored. Here, we investigated the role of IRF1 in osteoarthritis (OA), a condition marked by senescence and chronic joint inflammation. METHODS: OA progression was examined in wild-type and Irf1-/- mice using histologic assessments and microcomputed tomography analysis of whole-joint OA manifestations and behavioral assessments of joint pain. An integrated analysis of assay for transposase-accessible chromatin with sequencing and whole transcriptome data was conducted for the functional assessment of IRF1 in chondrocytes. The role of IRF1 in DNA repair and senescence was investigated by assaying γ-H2AX foci and senescence-associated beta-galactosidase activity. RESULTS: Our genome-wide investigation of IRF1 footprinting in chondrocytes revealed its primary occupancies in the promoters of DNA repair genes without noticeable footprint patterns in those of interferon-responsive genes. Chondrocytes lacking IRF1 accumulated irreversible DNA damage under oxidative stress, facilitating their entry into cellular senescence. IRF1 was down-regulated in the cartilage of human and mouse OA. Although IRF1 overexpression did not elicit an inflammatory response in joints or affect OA development, genetic deletion of Irf1 caused enhanced chondrocyte senescence and exacerbated post-traumatic OA in mice. CONCLUSION: IRF1 offers DNA damage surveillance in chondrocytes, protecting them from oxidative stress associated with OA risk factors. Our study provides a crucial and cautionary perspective that compromising IRF1 activity renders chondrocytes vulnerable to cellular senescence and promotes OA development.

Natural course of talar avascular necrosis during short-term follow-up and factors associated with Disease progression.

BACKGROUND: This retrospective cohort study aimed to investigate the natural history of talar avascular necrosis (AVN) during short-term outpatient follow-up and to identify the risk factors for progression to collapse and arthritic changes. METHODS: Thirty-four cases of talar AVN from 34 patients (15 males, 19 females) were included. The mean age of the patients was 48.9 years (SD 16.0 years) and the mean follow-up period was 39.5 months (SD 42.0 months). The patients were divided into two groups i.e., progression and non-progression groups. The progression group consisted of those who showed aggravation of the Ficat stage during the follow-up period or advanced arthritis of the ankle joint (Ficat stage 4) at presentation. Demographic data and information regarding BMI, medical comorbidities, trauma history, bilaterality, and location of the lesion (shoulder vs. non-shoulder lesions) were collected. Following the univariate analysis, a binary logistic regression analysis was performed. RESULTS: The location of the talar AVN was the only significant factor (p = 0.047) associated with disease progression. A total of 14.3% (2 of 14) of the central (non-shoulder) talar AVN lesions showed progression, while 50% (10 of 20) of shoulder lesions aggravated during follow-up. Age, sex, bilaterality, medical comorbidities, and trauma history were not associated with progressive talar collapse or subsequent arthritic changes in talar AVN. CONCLUSIONS: Conservative treatment should be considered for a central lesion of the talar AVN because it tends to remain stable without progression. A more comprehensive study with a larger study population is required to establish the surgical indications for talar AVN. LEVEL OF EVIDENCE: Prognostic level III.