Points to consider when developing drugs for dry eye syndrome

Changes in both the social environment (e.g., the increased use of electronic media) and the atmospheric environment (e.g., air pollution and dust) have contributed to an increasing incidence of eye disease and an increased need for eye care. Notably, the signs and symptoms of dry eye syndrome can impact the daily quality of life for various age groups, including the elderly, and usually requires active treatment. The symptoms of dry eye syndrome include tear film instability, hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities. As treatments for dry eye are being developed, a standardized guideline is needed to increase the efficiency of drug development and improve the quality of clinical trial data. In this paper, we present general considerations for the pharmaceutical industry and clinical trial investigators designing clinical trials focused on the development of drugs to treat dry eye syndrome.

Probiotic supplementation has sexdependent effects on immune responses in association with the gut microbiota in community-dwelling older adults:a randomized, double-blind, placebocontrolled, multicenter trial

BACKGROUND/OBJECTIVES@#Probiotics have been suggested as potent modulators of agerelated disorders in immunological functions, yet little is known about sex-dependent effects of probiotic supplements. Therefore, we aimed to investigate sex-dependent effects of probiotics on profiles of the gut microbiota and peripheral immune cells in healthy older adults. @*SUBJECTS/METHODS@#In a randomized, double-blind, placebo-controlled, multicenter trial, healthy elderly individuals ≥ 65 yrs old were administered probiotic capsules (or placebo) for 12 wk. Gut microbiota was analyzed using 16S rRNA gene sequencing and bioinformatic analyses. Peripheral immune cells were profiled using flow cytometry for lymphocytes (natural killer, B, CD4 + T, and CD8 + T cells), dendritic cells, monocytes, and their subpopulations. @*RESULTS@#Compared with placebo, phylum Firmicutes was significantly reduced in the probiotic group in women, but not in men. At the genus level, sex-specific responses included reductions in the relative abundances of pro-inflammatory gut microbes, including Catabacter and unclassified_Coriobacteriales, and Burkholderia and unclassified Enterobacteriaceae, in men and women, respectively. Peripheral immune cell profiling analysis revealed that in men, probiotics significantly reduced the proportions of dendritic cells and CD14 + CD16 - monocytes; however, these effects were not observed in women. In contrast, the proportion of total CD4 + T cells was significantly reduced in women in the probiotic group. Additionally, serum lipopolysaccharide-binding protein levels showed a decreasing tendency that were positively associated with changes in gut bacteria, including Catabacter (ρ = 0.678, P < 0.05) and Burkholderia (ρ = 0.673, P < 0.05) in men and women, respectively. @*CONCLUSIONS@#These results suggest that probiotic supplementation may reduce the incidence of inflammation-related diseases by regulating the profiles of the gut microbiota and peripheral immune cells in healthy elders in a sex-specific manner.

Magnetic resonance imaging features of syringobulbia in small breed dogs

Syringobulbia is a rare neurological disorder characterized by a fluid-filled cavity in the brainstem. In this study, clinical signs, features on magnetic resonance imaging (MRI), and the diseases present concurrently with syringobulbia were investigated in 33 small breed dogs. Most dogs (97%) had concurrent syringomyelia, and some dogs (24%) presented with vestibular or cranial nerve symptoms associated with the medulla oblongata. MRIs revealed slit-like, bulbous, and vertical linear shapes of the cavities on T2-weighted hyperintense and T1-weighted hypointense signals similar to the cerebrospinal fluid. Chiari-like malformations were identified in all dogs. This study highlights the association of syringobulbia with syringomyelia and Chiari-like malformations in small breed dogs with or without brainstem-associated clinical signs.

Comparison of Veno-arterial Extracorporeal Membrane Oxygenation Configurations for Patients Listed for Heart Transplantation

Background and Objectives@#Veno-arterial extracorporeal membrane oxygenation (VAECMO) as a bridge to eventual heart transplantation (HT) is increasingly used worldwide.However, the effect of different VA-ECMO types on HT outcomes remains unclear. @*Methods@#This was a retrospective observational study of 111 patients receiving VA-ECMO and awaiting HT. We assessed 3 ECMO configuration groups: peripheral (n=76), central (n=12), and peripheral to central ECMO conversion (n=23). Cox proportional hazards regression and landmark analysis were conducted to analyze the effect of the ECMO configuration on HT and in-hospital mortality rates. We also evaluated adverse events during ECMO support. @*Results@#HT was performed in the peripheral (n=48, 63.2%), central (n=10, 83.3%), and conversion (n=11, 47.8%) ECMO groups (p=0.133) with a median interval of 10.5, 16, and 30 days, respectively (p<0.001). The cumulative incidence of HT was significantly lower in the conversion group (hazard ratio, 0.292, 95% confidence interval, 0.145–0.586, p=0.001).However, there was no difference in in-hospital mortality (log-rank p=0.433). In the landmark analysis, in-hospital mortality did not differ significantly among the 3 groups.Although we did note a trend toward lower HT in the conversion group, the difference was not statistically significant. Surgical site bleeding occurred mainly in the central, while limb ischemia occurred mainly in the peripheral groups. @*Conclusions@#We suggest that if patients are being stably supported with their initial ECMO configuration, whether it is central or peripheral, it should be maintained, and ECMO conversion should only be cautiously performed when necessary.

Functional Insufficiency of Mitral and Tricuspid Valves Associated With Atrial Fibrillation: Impact of Postoperative Atrial Fibrillation Recurrence on Surgical Outcomes

Background and Objectives@#To identify the factors associated with adverse outcomes following surgery for functional insufficiency of the mitral valve (MV) or tricuspid valve (TV) associated with atrial fibrillation (AF). @*Methods@#We evaluated 100 patients (age, 66.5±10.0 years; 47 males) who consecutively underwent surgery for functional insufficiency of the MV or TV associated with AF between January 2000 and December 2020 at our center. The primary outcome was a composite endpoint of all-cause death, valve reoperation, congestive heart failure (CHF) requiring rehospitalization, and stroke. @*Results@#During follow-up (532 patients-years [PYs]), adverse events included death in 16 (3.0%/yr), MV reoperation in 1 (0.2%/yr), CHF in 14 (2.6%/yr), and stroke in 5 (0.9%/yr) patients, demonstrating a 5-year rate of freedom from the primary endpoint of 69.5%. The rate of postoperative AF was high even in those who underwent AF ablation (n=92), with cumulative rates of 48.1% at 1 year and 60.2% at 5 years. In multivariable analyses, the primary outcome was significantly associated with age (adjusted hazard ratio [aHR], 1.06; 95% confidence interval [CI], 1.02–1.10; p=0.005), chronic kidney disease (aHR, 7.76; 95% CI, 2.28–26.38;p=0.001), left atrial appendage exclusion (aHR, 0.35; 95% CI, 0.16–1.78; p=0.010), and postoperative AF as a time-varying covariate (aHR, 3.33; 95% CI, 1.50–7.40; p=0.003). @*Conclusion@#Among patients undergoing surgery for functional atrioventricular insufficiency associated with AF, a significant proportion showed recurrence of AF over time after concomitant AF ablation, which was significantly associated with poor clinical outcomes.

The Comparison of Long-term Surgical Results for Sensory Exotropia and Comitant Exotropia

Purpose@#To compare the long-term surgical outcomes of patients with sensory and concomitant exotropia and to define the factors associated with successful surgical outcomes in those with sensory exotropia. @*Methods@#The medical records of patients with sensory exotropia who underwent operations and were followed-up for at least 2 years were retrospectively reviewed. We enrolled patients exhibiting only best-corrected visual acuities ≤ 20/100 of the operated eyes. Surgical success was defined as a final distance deviation < 10 prism diopters (PD) with the eye in the primary position. Twenty-eight patients operated upon to treat sensory exotropia and 28 who underwent operations to treat concomitant exotropia who did not differ in terms of the gaze deviation angle were matched in terms of age, sex, and the preoperative distance and near distributions; their surgical outcomes were compared. Factors affecting such outcomes were identified using a multivariate Cox’s proportional hazards model. @*Results@#The mean follow-up times were 91.7 ± 45.8 months in the sensory and 42.6 ± 27.7 months in the concomitant exotropia groups. The cumulative probabilities of surgical success 2 years after surgery were 74.5% in the sensory and 74.4% in the intermittent exotropia groups, thus not significantly different (p = 0.988). The Cox’s proportional hazard model showed that a greater difference between the preoperative distant and near deviations was associated with recurrence (p = 0.091). @*Conclusions@#The long-term surgical outcomes of patients with sensory and concomitant exotropia were comparable. A high-level near-distance disparity increased the risk of recurrence.

A Randomized Phase III Study of Patients With Advanced Gastric Adenocarcinoma Without Progression After Six Cycles of XELOX (Capecitabine Plus Oxaliplatin) Followed by Capecitabine Maintenance or Clinical Observation

Purpose@#Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. @*Materials and Methods@#Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. @*Results@#Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250–0.890; P=0.020). @*Conclusions@#After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

Simulation Method for the Physical Deformation of a Three-Dimensional Soft Body in Augmented Reality-Based External Ventricular Drainage / 대한의료정보학회지

Objectives@#Intraoperative navigation reduces the risk of major complications and increases the likelihood of optimal surgical outcomes. This paper presents an augmented reality (AR)-based simulation technique for ventriculostomy that visualizes brain deformations caused by the movements of a surgical instrument in a three-dimensional brain model. This is achieved by utilizing a position-based dynamics (PBD) physical deformation method on a preoperative brain image. @*Methods@#An infrared camera-based AR surgical environment aligns the real-world space with a virtual space and tracks the surgical instruments. For a realistic representation and reduced simulation computation load, a hybrid geometric model is employed, which combines a high-resolution mesh model and a multiresolution tetrahedron model. Collision handling is executed when a collision between the brain and surgical instrument is detected. Constraints are used to preserve the properties of the soft body and ensure stable deformation. @*Results@#The experiment was conducted once in a phantom environment and once in an actual surgical environment. The tasks of inserting the surgical instrument into the ventricle using only the navigation information presented through the smart glasses and verifying the drainage of cerebrospinal fluid were evaluated. These tasks were successfully completed, as indicated by the drainage, and the deformation simulation speed averaged 18.78 fps. @*Conclusions@#This experiment confirmed that the AR-based method for external ventricular drain surgery was beneficial to clinicians.

Short-term effect of growth hormone treatment in childhood leukemia survivors with growth hormone deficiency

Purpose@#Survivors of childhood leukemia are at risk of growth impairment due to intensive chemotherapy and radiation treatments. This study investigated the auxological and biochemical characteristics of childhood leukemia survivors diagnosed with growth hormone deficiency (GHD) and the changes in these parameters after 1 year of growth hormone (GH) treatment. @*Methods@#A total of 24 children diagnosed with GHD after leukemia treatment was analyzed. Clinical and biochemical data were collected retrospectively at leukemia diagnosis, GHD diagnosis, and 1 year after GH treatment. Standard deviation score (SDS) was calculated based on the age- and gender-adjusted population. @*Results@#Of the 24 children included in this study, 19 received GH treatment. The median age at GHD diagnosis was 12.3 years, and the median delay in bone age was 1.46 years. Height SDS decreased from -0.69 at leukemia diagnosis to -2.58 at GHD diagnosis (P<0.001). The change in height SDS with and without GH for 1 year was 0.35 and -0.21, respectively (P=0.044). In regression analyses, higher height SDS at GHD diagnosis and a smaller decrease of the height SDS between leukemia and GHD diagnoses were positively correlated with height SDS after GH treatment. @*Conclusion@#GH treatment could be beneficial and safe for improving height in childhood leukemia survivors with GHD. Height SDS at GHD diagnosis and reduction of height SDS between leukemia and GHD diagnosis could be potential factors in predicting the therapeutic effects. Close auxological monitoring is recommended for any childhood leukemia survivors who experience posttreatment height decline.

Pharmacological Management of Germinal Matrix-Intraventricular Hemorrhage

Germinal matrix-intraventricular hemorrhage (GM-IVH) is among the devastating neurological complications with mortality and neurodevelopmental disability rates ranging from 14.7% to 44.7% in preterm infants. The medical techniques have improved throughout the years, as the morbidity-free survival rate of very-low-birth-weight infants has increased; however, the neonatal and long-term morbidity rates have not significantly improved. To this date, there is no strong evidence on pharmacological management on GM-IVH, due to the limitation of well-designed randomized controlled studies. However, recombinant human erythropoietin administration in preterm infants seems to be the only effective pharmacological management in limited situations. Hence, further high-quality collaborative research studies are warranted in the future to ensure better outcomes among preterm infants with GM-IVH.

Characteristics of Focused Ultrasound Mediated Blood-Brain Barrier Opening in Magnetic Resonance Images

Objective@#: The blood-brain barrier (BBB) is an obstacle for molecules to pass through from blood to the brain. Focused ultrasound is a new method which temporarily opens the BBB, which makes pharmaceutical delivery or removal of neurodegenerative proteins possible. This study was demonstrated to review our BBB opening procedure with magnetic resonance guided images and find specific patterns in the BBB opening. @*Methods@#: In this study, we reviewed the procedures and results of two clinical studies on BBB opening using focused ultrasound regarding its safety and clinical efficacy. Magnetic resonance images were also reviewed to discover any specific findings. @*Results@#: Two clinical trials showed clinical benefits. All clinical trials demonstrated safe BBB opening, with no specific side effects. Magnetic resonance imaging showed temporary T1 contrast enhancement in the sonication area, verifying the BBB opening. Several low-signal intensity spots were observed in the T2 susceptibility-weighted angiography images, which were also reversible and temporary. Although these spots can be considered as microbleeding, evidence suggests these are not ordinary microbleeding but an indicator for adequate BBB opening. @*Conclusion@#: Magnetic resonance images proved safe and efficient BBB opening in humans, using focused ultrasound.

Non-Arteritic Ischemic Optic Neuropathy Following COVID-19 Vaccination in Korea: A Case Series

Background@#To report the clinical manifestations of non-arteritic anterior ischemic optic neuropathy (NAION) cases after coronavirus disease 2019 (COVID-19) vaccination in Korea. @*Methods@#This multicenter retrospective study included patients diagnosed with NAION within 42 days of COVID-19 vaccination. We collected data on vaccinations, demographic features, presence of vascular risk factors, ocular findings, and visual outcomes of patients with NAION. @*Results@#The study included 16 eyes of 14 patients (6 men, 8 women) with a mean age of 63.5 ± 9.1 (range, 43–77) years. The most common underlying disease was hypertension, accounting for 28.6% of patients with NAION. Seven patients (50.0%) had no vascular risk factors for NAION. The mean time from vaccination to onset was 13.8 ± 14.2 (range, 1–41) days. All 16 eyes had disc swelling at initial presentation, and 3 of them (18.8%) had peripapillary intraretinal and/or subretinal fluid with severe disc swelling. Peripapillary hemorrhage was found in 50% of the patients, and one (6.3%) patient had peripapillary cotton-wool spots. In eight fellow eyes for which we were able to review the fundus photographs, the horizontal cup/ disc ratio was less than 0.25 in four eyes (50.0%). The mean visual acuity was logMAR 0.6 ± 0.7 at the initial presentation and logMAR 0.7 ± 0.8 at the final visit. @*Conclusion@#Only 64% of patients with NAION after COVID-19 vaccination have known vascular and ocular risk factors relevant to ischemic optic neuropathy. This suggests that COVID-19 vaccination may increase the risk of NAION. However, overall clinical features and visual outcomes of the NAION patients after COVID-19 vaccination were similar to those of typical NAION.

Factors affecting bone mineral density in children and adolescents with secondary osteoporosis

Purpose@#This study aimed to investigate the clinical factors associated with bone mineral density (BMD) among children and adolescents with osteoporosis secondary to treatment for underlying clinical conditions. @*Methods@#We retrospectively reviewed the medical records of patients aged 10–18 years and evaluated them for lumbar spine BMD (LSBMD) after treatment for underlying diseases, including hemato-oncologic, rheumatologic system, and inflammator y bowel diseases. LSBMD measured by dual-energy x-ray absorptiometry (DXA) performed from March 2019 to March 2021 was evaluated. We analyzed 117 patients who underwent initial DXA after treatment for underlying diseases. @*Results@#Subjects in this study had multiple underlying diseases: hemato-oncologic (78.6%), rheumatologic (11.1%), and inflammatory bowel diseases (10.3%). There was no significant association between the z-score and bone metabolic markers (P>0.05). However, higher cumulative glucocorticoid (GC) dose significantly reduced LSBMD z-score (P=0.029). Moreover, the association between cumulative dose of GC and initial z-score of LSBMD was significant in logarithmic regression analysis (P=0.003, R2=0.149). GC accumulation was a significant risk factor for vertebral fracture when the initial BMD was evaluated after treatment (P=0.043). Bone metabolic markers did not significantly influence the risk of vertebral fracture. @*Conclusion@#Initial bone mass density of the lumbar spine evaluated after long-term GC use for underlying diseases is a predictor of further vertebral fractures.

Successful treatment of a patient with recurrent metastatic clear cell carcinoma of the uterine cervix

Clear cell carcinoma (CCC) of the uterine cervix is a rare gynecologic cancer that accounts for 4–9% of adenocarcinoma of the uterine cervix. Two types of uterine cervical CCCs are known: A type that is associated with in utero exposure to diethylstilbestrol (DES) and idiopathic type that is unrelated to DES exposure. Due to its rare incidence, the clinical behavior and pathological characteristics of CCCs are not fully described and treatment recommendations are not standardized. Moreover, only a few cases are reported on the recurrent metastatic CCCs and the results of various treatment trials are inconsistent. We present a case of successfully treated idiopathic metastatic CCC of the uterine cervix that recurred after concurrent chemoradiotherapy.

Rotational Vertebral Artery Syndrome (Bow Hunter’s Syndrome): A Rare Differential Diagnosis in Patients With Syncope / 대한신경손상학회지

Syncope is a common symptom in clinical practice. Rotational vertebral artery occlusion syndrome, also referred to as Bow Hunter’s syndrome (BHS), is a rare condition associated with syncope and is caused by mechanical occlusion or stenosis secondary to mechanical compression of the vertebral artery during head rotation. BHS is associated with a multifactorial etiology; however, in most cases, this condition is attributed to degenerative changes. A 53-year-old man visited our hospital for the evaluation of fainting and dizziness episodes that occurred when he turned his head. Evaluation as an outpatient in the Department of Neurology showed a positive result on the Frenzel goggle test. Transfemoral cerebral angiography performed at the Department of Neurosurgery revealed stenosis of the proximal right vertebral artery. Complete occlusion of the vertebral artery was observed, and the head was turned to the right. Decompression and fusion were performed, and the contributory lesion was completely removed. Postoperative imaging confirmed complete removal of the spur and sufficient vertebral artery decompression; the patient’s symptoms resolved postoperatively.

Adrenocortical carcinoma and a sporadic MEN1 mutation in a 3-year-old girl: a case report

Childhood adrenocortical carcinoma (ACC) is a rare disease that is mostly linked to familial cancer syndrome. Although the prevalence of ACC is extremely low in children, it is clinically important to diagnose ACC early because age and tumor stage are closely related to prognosis. From this perspective, understanding the underlying genetics and possible symptoms of ACC is crucial in managing ACC with familial cancer syndromes. In this report, we present the case of a 3-year-old girl who initially presented with symptoms of precocious puberty and was later found to have ACC by imaging analysis. On genetic analysis, the patient was found to have a MEN1 gene mutation. MEN1 mutations are found in patients with multiple endocrine neoplasia type 1 (MEN1), usually precipitating multiple endocrine tumors, including pituitary adenoma, parathyroid hyperplasia, and adrenal tumors. Although MEN1 mutation is usually inherited in an autosomal dominant manner, neither of the patient’s parents had the same mutation, making hers a case of sporadic MEN1 mutation with initial presentation of ACC. The clinical course and further investigations of this patient are discussed in detail in this report.

Dual Pallidal and Thalamic Deep Brain Stimulation for Complex Ipsilateral Dystonia

Purpose@#Globus pallidus pars interna (GPi) has become an established target for deep brain stimulation (DBS) in dystonia. Previous studies suggest that targeting the ventralis oralis (Vo) complex nucleus improves dystonic tremor or even focal dystonia. Research has also demonstrated that multi-target DBS shows some benefits over single target DBS. In this study, we reviewed patients who had undergone unilateral DBS targeting the GPi and Vo. @*Materials and Methods@#Five patients diagnosed with medically refractory upper extremity dystonia (focal or segmental) underwent DBS. Two DBS electrodes each were inserted unilaterally targeting the ipsilateral GPi and Vo. Clinical outcomes were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and Disability Rating Scale. @*Results@#BFMDRS scores decreased by 55% at 1-month, 56% at 3-month, 59% at 6-month, and 64% at 12-month follow up. Disability Rating Scale scores decreased 41% at 1-month, 47% at 3-month, 50% at 6-month, and 60% at 12-month follow up. At 1 month after surgery, stimulating both targets improved clinical scores better than targeting GPi or Vo alone. @*Conclusion@#Unilateral thalamic and pallidal dual electrode DBS may be as effective or even superior to DBS of a single target for dystonia. Although the number of patients was small, our results reflected favorable clinical outcomes.

Pericardial Versus Porcine Valves for Surgical Aortic Valve Replacement

Background and Objectives@#There still are controversies on which type between bovine pericardial and porcine valves is superior in the setting of aortic valve replacement (AVR). This study aims to compare clinical outcomes of AVR using between pericardial or porcine valves. @*Methods@#The study involved consecutive 636 patients underwent isolated AVR using stented bioprosthetic valves between January 2000 and May 2016. Of these, pericardial and porcine valves were implanted in 410 (pericardial group) and 226 patients (porcine group), respectively. Clinical outcomes including survival, structural valve deterioration (SVD) and trans-valvular pressure gradient were compared between the groups. To adjust for potential selection bias, inverse probability treatment weighting (IPTW) was conducted. @*Results@#The mean follow-up duration was 60.1±50.2 months. There were no significant differences in the rates of early mortality (3.1% vs. 3.1%; p=0.81) and SVD (0.3%/patient-year [PY] vs. 0.5%/PY; p=0.33) between groups. After adjustment using IPTW, however, landmark mortality analyses showed a significantly lower late (>8 years) mortality risk in pericardial group over porcine group (hazard ratio [HR], 0.61; 95% confidence interval, [CI] 0.41–0.90; p=0.01) while the risks of SVD were not significantly difference between groups (HR, 0.45; 95% CI, 0.12–1.70; p=0.24). Mean pressure gradient across prosthetic AV was lower in the Pericardial group than the Porcine group at both immediate postoperative point and latest follow-up (p values <0.001). @*Conclusions@#In patients undergoing bioprosthetic surgical AVR, bovine pericardial valves showed superior results in terms of postoperative hemodynamic profiles and late survival rates over porcine valves.

Modified Harada-Ito Procedure with Intraoperative Adjustable Sutures Using a Mendez Ring for Excyclotorsion

Purpose@#We report a case of using a modified Harada-Ito procedure with intraoperative adjustment via a Mendez ring in a patient with bilateral superior oblique palsy, resulting in satisfactory postoperative outcomes.Case summary: A 47-year-old male patient presented with bilateral diplopia after cerebral hemorrhage. Bilateral superior oblique palsy was diagnosed, and double Maddox rod tests confirmed 20° of excyclotorsion in both eyes. After 6 months of observation, surgical correction was attempted. To check the amount of cyclodeviation, a modified Harada–Ito procedure was performed on the superior oblique muscle after marking at the 6 and 12 o'clock positions of the corneal limbus. Following the procedure, a Mendez ring was placed on the limbus to check for the amount of incyclotorsion. Thirty degrees of incyclotorsion was aimed at both eyes, and a 5-mm resection of the right superior oblique tendon was performed for additional correction. There was no complaint of diplopia at 6 months postoperatively, and no deviation was observed. @*Conclusions@#A modified Harada-Ito procedure with intraoperative adjustment using a Mendez ring effectively corrected excyclotorsion with torsional diplopia.

Extensive Leukoencephalopathy in Spastic Paraplegia Type 4: Possible Role of Cerebral Autosomal Arteriopathy With Subcortical Infarcts and Leukoencephelopathy

Despite recent advances in next-generation sequencing, the underlying etiology of adult-onset leukoencephalopathy has been difficult to elucidate. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a representative hereditary adult-onset leukoencephalopathy associated with vasculopathy. Leukoencephalopathy in spastic paraplegia type 4 (SPG4) is known to be rare, but it might be underestimated because most spastic paraplegia with leukoencephalopathy is rarely considered. We report a case of co-occurring SPG4 and CADASIL. A 61-year-old male presented with sudden visual impairment after a headache. He showed a spastic gait and had a family history with similar symptoms. An SPG4 gene mutation and a pathogenic variant in the NOTCH3 gene were found. This case shows that the diverse and complex clinical manifestations of patients with extensive leukoencephalopathy are related to more than one gene mutation. We also suggest the necessity for relevant genetic tests in the diagnosis of adult-onset leukoencephalopathy.