Sensitivity, Specificity, and Cutoff Identifying Optic Atrophy by Macular Ganglion Cell Layer Volume in Syndromic Craniosynostosis.

PURPOSE: To determine the sensitivity, specificity, and cutoff of macular ganglion cell layer (GCL) volume consistent with optic atrophy in children with syndromic craniosynostosis and to investigate factors independently associated with reduction in GCL volume. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Patients with syndromic craniosynostosis evaluated at Boston Children's Hospital (2010-2022) with reliable macular OCT scans. METHODS: The latest ophthalmic examination that included OCT macula scans was identified. Age at examination, sex, ethnicity, best-corrected logarithm of the minimum angle of resolution (logMAR) visual acuity, cycloplegic refraction, and funduscopic optic nerve appearance were recorded in addition to history of primary or recurrent elevation in intracranial pressure (ICP), Chiari malformation, and obstructive sleep apnea (OSA). Spectral-domain OCT software quantified segmentation of macula retinal layers and was checked manually. MAIN OUTCOME MEASURES: The primary outcome was determining sensitivity, specificity, and optimal cutoff of GCL volume consistent with optic atrophy. The secondary outcome was determining whether previously elevated ICP, OSA, Chiari malformation, craniosynostosis diagnosis, logMAR visual acuity, age, or sex were independently associated with lower GCL volume. RESULTS: Median age at examination was 11.9 years (interquartile range, 8.5-14.8 years). Fifty-eight of 61 patients (112 eyes) had reliable macula scans, 74% were female, and syndromes represented were Apert (n = 14), Crouzon (n = 17), Muenke (n = 6), Pfeiffer (n = 6), and Saethre-Chotzen (n = 15). Optimal cutoff identifying optic atrophy was a GCL volume < 1.02 mm3 with a sensitivity of 83% and specificity of 77%. Univariate analysis demonstrated that significantly lower macular GCL volume was associated with optic atrophy on fundus examination (P < 0.001), Apert syndrome (P < 0.001), history of elevated ICP (P = 0.015), Chiari malformation (P = 0.001), OSA (P < 0.001), male sex (P = 0.027), and worse logMAR visual acuity (P < 0.001). Multivariable median regression analysis confirmed that only OSA (P = 0.005), optic atrophy on fundus examination (P = 0.003), and worse logMAR visual acuity (P = 0.042) were independently associated with lower GCL volume. CONCLUSIONS: Surveillance for optic atrophy by GCL volume may be useful in a population where cognitive skills can limit acquisition of other key ophthalmic measures. It is noteworthy that OSA is also associated with lower GLC volume in this population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Two siblings with GAPO syndrome: Ophthalmic presentation and histopathologic findings.

BACKGROUND: GAPO syndrome (growth retardation, alopecia, pseudoanodontia, optic atrophy) is a rare, autosomal recessive connective tissue disorder with only 60 reported cases. Ophthalmic manifestations vary and include hypertelorism, optic atrophy, and glaucoma. There have been three reported cases of GAPO syndrome with craniosynostosis. MATERIALS/METHODS: We describe two new siblings with GAPO syndrome and craniosynostosis and the first histopathologic analysis of Tenon's capsule and extraocular muscle in this syndrome. RESULTS: Both siblings presented with papilledema and V-pattern strabismus in addition to the alopecia, brittle eyelashes, growth retardation, and pseudoanodontia that characterize GAPO syndrome. Cranial vault expansion, though successful, was complicated by lack of distinct periosteal layers, thin dural adherence to bone, and extensive venous bleeding. Tenons encountered during strabismus surgery was inelastic and highly vascular. Histopathological analysis revealed hyalinization of Tenon's and a thickened, homogenized, amorphous appearance, similar to the extracellular matrix abnormalities described in skin and other organs Histopathological analysis of extraocular muscle was, in contrast, unremarkable. CONCLUSIONS: GAPO impacts the extracellular matrix of Tenon's resulting in inelasticity and hypervascularity. Ophthalmologists should be mindful of these aberrant characteristics when planning surgery in this population.

Barriers and facilitators to the implementation of a novel web-based sleep apnea management platform.

STUDY OBJECTIVE: Obstructive sleep apnea (OSA) is a highly prevalent yet underdiagnosed disorder affecting US military Veterans. The Remote Veterans Apnea Management Platform (REVAMP) is a web-based OSA management program created to improve access to care. REVAMP was launched within the Veterans Health Administration (VHA) in July 2017, with variable patient recruitment rates (from 0 to 573 patients per site) at the first 10 Veterans Affairs (VA) medical centers (Wave-1 sites). This study aimed to examine the contextual circumstances surrounding the implementation of REVAMP from the provider perspective to inform strategies to increase its uptake at future rollout sites. METHODS: A purposive sample of REVAMP site leaders from the Wave-1 sites was recruited with additional staff members being solicited as well. Semi-structured interviews were conducted. Two independent coders reviewed individual transcripts using content analysis to identify emerging themes. RESULTS: Fifteen individuals from Wave-1 sites were interviewed. Implementation of REVAMP was facilitated by the presence of leadership support, staff, and time dedicated to REVAMP, and perceived usefulness of REVAMP by staff as well as positive feedback from the Veterans using REVAMP. The difficulty of supporting Veteran creation of login credentials to the program and integrating REVAMP into the existing workflow were major barriers to its implementation. CONCLUSION: Improving leadership engagement, simplifying the enrollment process, and enhancing the medical staff experience through shared best practice alerts were identified as actions needed to improve the penetration of REVAMP at future rollout sites.

Early Quantitative Partial Weight-Bearing Exercise After Periarticular Fractures of the Tibia Using a Lower-Body Positive-Pressure Treadmill: A Case Series.

The partial weight-bearing protocol after lower limb fracture is an important issue in postoperative rehabilitation. Because it is difficult to quantify the actual weight load and provide a constant weight, the protocol is unestablished. By training with a lower-body positive-pressure treadmill and using an in-shoe pressure-measuring device, partial weight-bearing exercise can be performed with quantified loads. This case series illustrates the applicability of an early quantitative partial weight-bearing rehabilitation program using lower-body positive-pressure treadmill with an in-shoe pressure-measuring device after periarticular tibial fractures, which provides a quantitatively predetermined constant load.

Association between adherence to continuous positive airway pressure treatment and cost among medicare enrollees.

OBJECTIVE: To analyze the cost associated with sleep apnea and effects of continuous positive airway pressure (CPAP) treatment on costs among fee-for-service Medicare beneficiaries. METHODS: Retrospective cohort design using 5% Medicare claims between 2006 and 2010. Medicare beneficiaries with and without sleep apnea diagnosis between 2007 and 2008 were identified and followed retrospectively for 2 years pre-index-date and 2 years post-index-date. We defined CPAP fill as at least one durable medical equipment claim for CPAP in 6-month period. At least three CPAP fills was defined as "full adherence," and one or two CPAP fills was "partial adherence." We used interrupted time series and generalized linear log-link models to study the association between sleep apnea, CPAP treatment, and costs. To minimize bias, we used propensity score and instrumental variables approach. RESULTS: Sleep apnea was associated with higher costs (odds ratio [OR] = 1.60; 95% confidence interval [CI] = 1.58, 1.63) compared to those without sleep apnea. Almost half of those with sleep apnea received CPAP treatment. Interrupted time series analysis indicated post level increase in mean monthly cost for full CPAP adherence group, partial CPAP adherence group and no-CPAP group. However, the increase was smallest for the full CPAP adherence group. Full CPAP adherence was associated with lower change in cost (OR = 0.92; 95% CI = 0.88, 0.97) compared to the no-CPAP group. CONCLUSIONS: Medicare beneficiaries with sleep apnea experience increased cost. Full adherence to CPAP treatment for sleep apnea was associated with lower increase in cost. These findings emphasize the need to effectively identify and treat sleep apnea in Medicare patients.

Impact of Obstructive Sleep Apnea on Optic Nerve Function in Patients With Craniosynostosis and Recurrent Intracranial Hypertension.

PURPOSE: Assessment of combined impact of intracranial hypertension (ICH) and obstructive sleep apnea (OSA) on optic nerve function in children with craniosynostosis (CS). DESIGN: Retrospective cross-sectional study. METHODS: Patients treated at Boston Children's Hospital for CS who had an ophthalmic examination that included pattern reversal (pr)VEP (2013-2014) and history of ICH based on direct measurement, papilledema, or classic features on neuroimaging and during cranial vault expansion were included. History of OSA was determined by polysomnography and associated conditions, including apnea and (adeno)tonsillectomy. Subjects were divided into 4 groups: group 1, resolved ICH absent history of OSA; group 2, resolved ICH with history of OSA; group 3, recurrent ICH absent history of OSA; and group 4, recurrent ICH with history of OSA. Predictor variables included latency of P100 component of pattern-reversal visual evoked potential, best-corrected visual acuity, optic nerve appearance, visual fields, and global retinal nerve fiber layer. Primary outcome was association of prolonged P100 latency with resolved vs recurrent ICH and OSA. RESULTS: Twenty-eight children met inclusion criteria (mean age 11.6 ± 6.9 years): group 1 (n = 3), group 2 (n = 6), group 3 (n = 8), and group 4 (n = 11). P100 latencies were not prolonged in groups 1 and 2. Three of 8 in group 3 and 9 of 11 in group 4 had prolonged P100 latency. Group 4 was significantly worse than group 3 (P = .005). CONCLUSIONS: History of OSA, in addition to recurrent ICH, is associated with greatest risk of optic neuropathy with CS. Ophthalmologists should encourage early management of OSA as well as ICH to optimize ophthalmic outcomes.

Increased risk for new-onset hypertension in midlife male snorers: The 14-year follow-up study.

While the association between sleep-related breathing disorders such as snoring and hypertension has been well established, it still remains unclear whether the association differs by age and gender. Therefore, in this 14-year follow-up study, we examined the independent association between self-reported snoring and the incidence of hypertension by gender and age groups in a large cohort of Korean adults. A total of 4,954 adults, aged 40-69 years, free of hypertension at baseline were enrolled. Participants were divided into three groups based on a self-reported snoring frequency: never; occasional (snoring <4 nights per week); and habitual snorer (snoring ≥4 nights). At baseline and biennial follow-up visits, blood pressure was measured by trained examiners. Incident hypertension was defined as the first occurrence at any follow-up examination where the participants had blood pressure ≥140/90 mmHg or were being treated with antihypertensive medication. After adjusting for known cardiovascular risk factors, only in men aged ≤45 years was habitual snoring significantly associated with a 1.5 times higher risk for incident hypertension than never snoring. In this age group, habitual snoring was significantly associated with increased risk for the development of hypertension, regardless of the presence of excessive daytime sleepiness. In women, snoring was not significantly associated with hypertension incidence in any age group. The present study suggests that young male snorers may be at high risk for the future development of hypertension, which has important clinical implications for early detection and treatment of snoring to reduce the burden of cardiovascular disease.

Patient Characteristics and Surgical Approach Impacting Simultaneous to Alternate Prism Cover Test Disparity After Exotropia Surgery: A Quantitative Look at the Difference in Motor Outcomes.

PURPOSE: To investigate the relationship between simultaneous prism and cover test (SPCT) and alternate prism and cover test (APCT) outcomes after exotropia surgery, and to identify characteristics associated with significant disparity between them. METHODS: Review of sensorimotor outcomes 2 to 6 months after exotropia surgery identified patients with alignment documented by both SPCT and APCT at the same examination. Two hundred seventy-four and 319 patients had both measurements recorded at distance and near, respectively. Correlation between the SPCT and APCT and range of APCT when the SPCT measurement was zero were determined. Patient characteristics studied for association with a difference between the SPCT and APCT exceeding known APCT test-retest variability included age, visual acuity, fusion, intermittency, pattern, preoperative and postoperative angle, and treatment with or without medial rectus resection. RESULTS: SPCT and APCT outcomes were strongly correlated (P < .001), significantly different (P < .001), and linearly related. The percentage of patients who were orthotropic (SPCT = 0) was 76% at distance and 80% at near. Misalignment of 10 prism diopters (PD) or less by the APCT was present in 92% of orthotropic patients at distance and 84% at near. Surgery without medial rectus resection (P = .015), larger preoperative angle (P = .003), intermittent exotropia (P = .028), and postoperative exotropia rather than esotropia (P < .001) were associated with a significant SPCT-APCT difference. CONCLUSIONS: Although a greater postoperative SPCT-APCT disparity was confirmed for patients with intermittent exotropia, it also independently associated with a larger preoperative deviation and surgery without medial rectus resection. Performing medial rectus resection, a surgeon's prerogative, provides more apparently consistent postoperative alignment characterized by less SPCT-APCT disparity. [J Pediatr Ophthalmol Strabismus. 2017;54(4):222-230.].

Goal-determined metrics to assess outcomes of exotropia surgery.

PURPOSE: To present a goal-determined methodology for monitoring outcomes after surgery for exotropia. METHODS: The goal-determined metric required surgeons to rank four possible goals preoperatively: (1) binocular potential, (2) restoration of eye contact, (3) diplopia control; and (4) torticollis management. Potential preoperative risk factors were noted. Goal-specific outcomes criteria were applied to the latest sensory-motor examination, 2-6 months after surgery. The medical records of patients who underwent surgery from 2007 to 2012 were retrospectively reviewed with respect to the goal-directed metric. RESULTS: A total of 852 patients were evaluated in the study period: 411 for restoration of eye contact; 347 for binocular potential; 78 for diplopia resolution; and16 for torticollis management. Excellent (62%) or good (16%) outcomes were achieved in 78%. Procedures to resolve diplopia (OR, 6.56; 95% CI, 3.39-12.68) and to restore eye contact (OR, 3.74; 95% CI, 2.65-5.29) were more likely to result in excellent outcomes than procedures to improve binocular potential. Simultaneous surgery for dissociated vertical deviation (OR, 0.38; 95% CI, 0.16-0.92) and preoperative near deviation ≥50(Δ) (OR, 0.27; 95% CI, 0.17-0.42) limited likelihood of an excellent outcome. Outcomes monitored by simultaneous rather than alternate prism and cover test were more likely graded excellent (OR, 5.16; 95% CI, 3.50-7.62). Applying motor criteria from the binocular potential goal to the entire cohort diminished putative outcomes (P < 0.001). CONCLUSIONS: Goal-determined metric monitoring outcomes of exotropia surgery provides outcomes germane to the reason for intervention, enables analysis of risk factors affecting outcomes, and facilitates reporting on heterogeneous populations.

Parent-reported symptoms of attention deficit hyperactivity disorder in children with intermittent exotropia before and after strabismus surgery.

PURPOSE: To investigate the symptoms of attention deficit hyperactivity disorder (ADHD) as reported by parents in children with intermittent exotropia [X(T)] and to determine whether strabismus surgery for X(T) affects ADHD symptoms. MATERIALS AND METHODS: Fifty-one consecutive children undergoing muscle surgery for X(T) were prospectively recruited. One parent of each child completed the ADHD rating scale IV (ADHD RS-IV) assessment consecutively before and one year after surgery. Patients whose preoperative scores were above the cut-off point, the 90th percentile based on a Korean sample, were regarded as demonstrating the ADHD trait. The impact of muscle surgery on ADHD symptoms was assessed by comparing the preoperative scores with the post-operative scores. RESULTS: Eight (15.7%) of the 51 patients demonstrated the ADHD trait. ADHD RS-IV scores following strabismus surgery significantly decreased in patients with the ADHD trait (p=0.014), while they did not differ in patients without the ADHD trait. Seven (87.5%) of the 8 patients with the ADHD trait showed improvement in their ADHD RS-IV scores after surgery. There was no difference in surgical success rates between X(T) patients with and without the ADHD trait. CONCLUSION: The ADHD trait was relatively common in children with X(T), and the parent-reported symptoms of the children with the ADHD trait improved after strabismus surgery. These results suggest that childhood X(T) may be one contributing factor to ADHD- related symptoms.

Practical aspects and efficacy of intraoperative adjustment in concomitant horizontal strabismus surgery.

PURPOSE: To analyze the practical aspects and advantages of one-stage adjustable surgery under topical anesthesia in concomitant horizontal strabismus. METHODS: A retrospective review of 363 patients was completed to assess (1) the frequency of need to perform adjustment, (2) the amount and pattern of adjustment, and (3) the final alignment at least 6 months after surgery. Intraoperative adjustment was performed strictly toward the aim of orthophoria or slight overcorrection (heterophoria < 6 prism diopters [PD]) while avoiding diplopia. RESULTS: Of the 363 patients, 261 (72%) required intraoperative adjustment. Of these, 85% of exotropes underwent a decreased amount of surgery compared with the standard amount, whereas 58% of esotropes underwent an increased amount of surgery. Forty-two patients underwent a one-muscle surgery instead of the scheduled two-muscle surgery, and all had less than 35 PD preoperative angle of deviation. Success rates were 83% in all patients with one-stage adjustable sutures and 87% in patients who underwent adjustment. In 42 patients with one-muscle surgery instead of two-muscle surgery, 32 (76%) obtained successful results. CONCLUSION: Intraoperative adjustment was effective in concomitant horizontal strabismus surgery and can provide the opportunity to avoid a large overcorrection, especially in cases with moderate angle horizontal muscle surgery.

Cannabinoid hyperemesis relieved by compulsive bathing.

Cannabinoid hyperemesis is a clinical syndrome characterized by repeated vomiting and associated learned compulsive hot water bathing behavior due to long-term marijuana use. Research has identified type 1 cannabinoid receptors in the intestinal nerve plexus that have an inhibitory effect on gastrointestinal motility. This inhibitory effect may lead to hyperemesis in marijuana users. The thermoregulatory role of endocannabinoids may be responsible for the patient's need to take hot showers. We report 2 cases of cannabinoid hyperemesis that demonstrate this unusual adverse effect of marijuana use.

The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A.

The immunosuppressive action of the calcineurin inhibitor cyclosporine A (CsA) stems from the inhibition of nuclear factor of activated T cells (NFAT) signaling in T cells. CsA is also used for the treatment of proteinuric kidney diseases. As it stands, the antiproteinuric effect of CsA is attributed to its immunosuppressive action. Here we show that the beneficial effect of CsA on proteinuria is not dependent on NFAT inhibition in T cells, but rather results from the stabilization of the actin cytoskeleton in kidney podocytes. CsA blocks the calcineurin-mediated dephosphorylation of synaptopodin, a regulator of Rho GTPases in podocytes, thereby preserving the phosphorylation-dependent synaptopodin-14-3-3 beta interaction. Preservation of this interaction, in turn, protects synaptopodin from cathepsin L-mediated degradation. These results represent a new view of calcineurin signaling and shed further light on the treatment of proteinuric kidney diseases. Novel calcineurin substrates such as synaptopodin may provide promising starting points for antiproteinuric drugs that avoid the serious side effects of long-term CsA treatment.

Outcomes of 6 hour part-time occlusion treatment combined with near activities for unilateral amblyopia.

PURPOSE: To evaluate the outcome of the part-time occlusion therapy with near activities in monocular amblyopic patients according to gender, age, severity of amblyopia, and the cause of amblyopia. METHODS: Fifty eight patients who were prescribed part-time occlusion therapy with near activity from July 1998 to October 2004, were included in this retrospective study. All patients were divided into groups by gender, age, severity of amblyopia, and the cause of amblyopia. Main outcome measures were best corrected visual acuity, line improvement, and success rate. RESULTS: At the end of patch therapy, visual acuity improved from baseline by an average of 3.2+/-2.5 lines (0.33+/-0.26 log MAR), and follow-up period was 19.71+/-14.61 months (1.62+/-1.20 years). At the last follow-up, visual acuity improved from baseline by an average of 3.7+/-2.4 lines (0.38+/-0.26 log MAR), and follow-up period was 37.41+/-25.83 months (3.08+/-2.12 years). The success rate was 86% (50 patients) at the end of patch therapy. In 44 patients out of 50 patients (88%), the visual acuity was maintained. While 43 patients out of 47 patients who were less than 7 years old (91%) achieved success, 7 patients out of 11 patients 7 years or older (64%) achieved success (p=0.035). CONCLUSIONS: Six-hour part-time occlusion treatment combined with near activities appears to be favorable in treating 58 children during follow-up of mean 3.08 years. The significant factor was the age at initial treatment.

Enhanced stereocomplex formation of poly(L-lactic acid) and poly(D-lactic acid) in the presence of stereoblock poly(lactic acid).

Stereoblock poly(lactic acid) (sb-PLA) is incorporated into a 1:1 polymer blend system of poly(L-lactic acid) (PLLA) and poly(D-lactic acid) (PDLA) that has a high molecular weight to study its addition effect on the stereocomplex (sc) formation of PLLA and PDLA. The ternary polymer blend films are first prepared by casting polymer solutions of sb-PLA, PLLA, and PDLA with different compositions. Upon increasing the content of sb-PLA in the blend films the sc crystallization is driven to a higher degree, while the formation of homo-chiral (hc) crystals is decreased. Lowering the molecular weight of the incorporated sb-PLA effectively increases the sc formation. Consequently, it is revealed that sb-PLA can work as a compatibilizer to improve the poor sc formation in the polymer blend of PLLA and PDLA.

Outcome study of two standard and graduated augmented modified Kestenbaum surgery protocols for abnormal head postures in infantile nystagmus.

BACKGROUND AND PURPOSE: Since Kestenbaum and Anderson, several ophthalmologists have reported the results of different surgical procedures, for abnormal head posture in infantile nystagmus. In this study, we tried to evaluate the surgical results of Parks' original 5-6-7-8 mm modified Kestenbaum procedure and our own 6-7-6-7 mm modified Kestenbaum procedure, designed to reduce some of the problems encountered with other variations of these techniques. METHODS: Medical records of 92 patients, who had modified Kestenbaum surgery (5-6-7-8 mm or 6-7-6-7 mm) at The Yonsei Medical Center, from March 1991 to September 2001 with a follow-up period of more than 6 months, were reviewed retrospectively. We compared Parks' modified Kestenbaum surgery (5- 6-7-8 mm) performed on 51 patients with our own modified Kestenbaum surgery (6-7-6-7 mm) on 41 patients. Each procedure was done with graded augmentation according to the amount of the face turn and the null point in electro-oculography. RESULTS: In the follow-up of an average 33 months, 45 out of 51 patients (88.2%) who underwent Parks' modified procedures showed face turn less than 10 degrees. In the follow-up of an average 29 months, 36 out of 41 patients (87.8%) with 6-7-6-7 mm procedure had face turn less than 10 degrees. CONCLUSIONS: We suggest that 6-7-6-7 mm modified Kestenbaum procedures with a graded augmentation may be a safe and efficient procedure to correct abnormal head posture in infantile nystagmus with a minimum decrease in ocular motility.