Efficacy of inverted inner limiting membrane flap technique for macular holes of ≤400 µm: A systematic review and meta-analysis.

PURPOSE: To evaluate the efficacy of inverted internal limiting membrane (ILM) flap technique in full-thickness macular holes (MHs) with a size of ≤400 µm compared to the ILM peeling technique. METHODS: Related literatures that compared inverted ILM flap and ILM peeling in MHs ≤ 400 µm were reviewed by searching electronic databases including Pubmed, EMbase, ClinicalTrials.gov, and Cochrane Library up to April 2023. The primary outcome measure was hole closure rate, and the secondary outcome measures were the mean postoperative best-corrected visual acuity (BCVA), retinal sensitivity, and outer status of the retinal layers, including the external limiting membrane and ellipsoid zone. The quality of the articles was assessed according to the revised version of the Cochrane risk-of-bias tool for randomized trials or the Newcastle-Ottawa scale. In the case of heterogeneity, a sensitivity analysis was conducted, and publication bias was visually evaluated using a funnel plot. RESULTS: This review included six studies with 610 eyes for the primary outcome and 385 eyes for the secondary outcomes, which were two randomized control trials and four retrospective studies. Pooled data revealed that the overall MH closure rate was 99.4% in the inverted ILM flap group and 96.2% in the ILM peeling group, without significant difference between the two groups (odds ratio = 3.91; 95% confidence interval, 0.82~18.69; P = 0.09). The inverted ILM flap technique did not have a favorable effect on the BCVA, retinal sensitivity, or recovery of the outer retinal layers. These results were consistent with those of the subgroup analysis of the different follow-up periods. No significant publication bias was observed. CONCLUSION: In eyes with MHs of ≤400 µm, both techniques demonstrated excellent surgical outcomes without significant differences. Therefore, surgical techniques can be selected according to surgeon preferences.

Factors Associated with Surgical Outcomes after Bilateral Lateral Rectus Recession in Children with Intermittent Exotropia.

Backgroud: To analyze the factors associated with surgical outcomes after bilateral rectus recession (BLR) in children with intermittent exotropia (IXT). Methods: A retrospective study was performed on 125 patients who had all received preoperative patch treatment with a ≥1 year follow-up. The surgical outcomes were grouped as success (esodeviation ≤5 PD to exodeviation ≤10 PD) or failure (esodeviation >5 PD or exodeviation >10 PD) according to the angle of deviation at 1 year postoperatively. The patients' magnitude of exodeviation, near and distant stereoacuity, and 3-mo patch responses were assessed. The factors associated with the surgical outcomes were determined using univariate and multivariate analyses. Results: Of the 125 patients, 102 (81.6%) and 23 (18.4%) were assigned to the success and failure groups, respectively. According to the univariate analysis, the absence of anisometropia, a smaller preoperative near exodeviation, a better near stereopsis, a smaller magnitude of deviation on day 1 postoperatively, and response to patching were significantly associated with surgical success for IXT after 1 year. In the multivariate analysis, distant esotropic deviation on day 1 postoperatively and response to patching were the factors affecting successful surgical outcomes. Conclusions: Esotropic distant deviation on day 1 postoperatively is a prognostic factor for favorable surgical outcomes. Preoperative patching could be a factor influencing surgical success in children with IXT.

Successful Management of Refractory Kimura Disease with CVP Chemotherapy: A Case Report.

BACKGROUND Kimura disease is a rare, chronic inflammatory disorder typically presenting as a painless mass in the head or neck and associated with elevated serum immunoglobulin E and blood and tissue eosinophilia. Generally benign, its management is not well-defined, but corticosteroids are a common initial treatment. We detail a case of refractory Kimura disease successfully managed with CVP (Cyclophosphamide, Vincristine, Prednisone) chemotherapy and no recurrence during 6 rounds of treatment. CASE REPORT A 64-year-old woman, previously diagnosed with Kimura disease, returned to the hospital with upper eyelid ptosis. Upon examination, a solid mass was palpable in her left upper eyelid. Peripheral blood tests confirmed elevated IgE levels at 356.0 IU/ml. An excisional biopsy showed infiltration of lymphocytes and eosinophils, consistent with Kimura disease. Despite undergoing corticosteroid treatment, surgical debulking, radiation, and immunosuppressant therapy, her condition worsened. Concerns were raised due to imaging features suggestive of lymphoma, although no malignancy was evident in subsequent biopsies. It was decided to manage the disease using CVP chemotherapy, leading to significant symptom improvement. There have been no recurrences during the 12-month follow-up period. CONCLUSIONS Kimura disease is typically benign and responsive to treatment, but it often recurs and can progress. When symptoms are not controlled with conventional treatments, including corticosteroids, immunosuppressants, radiation, and surgical debulking, chemotherapy may be a reasonable option even when no definite signs of malignancy is identified. Further research is needed to explore the utility of CHOP and CVP in managing uncontrolled Kimura disease.

Does a preterm labor-assessment algorithm improve preterm labor-related knowledge, clinical practice confidence, and educational satisfaction?: a quasi-experimental study.

PURPOSE: Preterm birth is increasing, and obstetric nurses should have the competency to provide timely care. Therefore, training is necessary in the maternal nursing practicum. This study aimed to investigate the effects of practice education using a preterm-labor assessment algorithm on preterm labor-related knowledge and clinical practice confidence in senior nursing students. METHODS: A pre-post quasi-experimental design with three groups was used for 61 students. The preterm-labor assessment algorithm was modified into three modules from the preterm-labor assessment algorithm by March of Dimes. We evaluated preterm labor-related knowledge, clinical practice confidence, and educational satisfaction. Data were analyzed with the paired t-test and repeated-measures analysis of variance. RESULTS: The practice education using a preterm-labor assessment algorithm significantly improved both preterm labor-related knowledge and clinical practice confidence (paired t=-7.17, p<.001; paired t=-5.51, p<.001, respectively). The effects of the practice education using a preterm-labor assessment algorithm on knowledge lasted until 8 weeks but decreased significantly at 11 and 13 weeks after the program, while the clinical practice confidence significantly decreased at 8 weeks post-program. CONCLUSION: The practice education using a preterm-labor assessment algorithm was effective in improving preterm labor-related knowledge and clinical practice confidence. The findings suggest that follow-up education should be conducted at 8 weeks, or as soon as possible thereafter, to maintain knowledge and clinical confidence, and the effects should be evaluated.

Prognostic significance of thyroid-stimulating hormone receptor antibodies in moderate-to-severe graves' orbitopathy.

Design: Retrospective study. Purpose: The purpose of this retrospective study was to assess the changes in thyroid-stimulating hormone receptor (TSH-R) antibody levels following treatment in patients with moderate-to-severe and active Graves' orbitopathy (GO) and to investigate the correlation between these antibodies and treatment response. Methods: The subjects of this study comprised of patients newly diagnosed with moderate-to-severe and active GO within the age range of 19 to 79 years. All participants underwent intravenous methylprednisolone (IVMP) therapy for a duration of 12 weeks. Patients with a clinical activity score (CAS) decrease to or less than 3 and no symptom recurrence for at least 3months after the last dose of IVMP were classified as "Group 1". Those with a CAS equal to or greater than 4 were classified as "Group 2". TSH-R antibody levels were measured prior to and following IVMP treatment and treatment response was evaluated after the completion of IVMP therapy. All patients were monitored for a minimum of 6 months post-treatment, with ocular examinations and laboratory tests at the initial visit being included in the analysis. Results: The medical records of the 96 patients with GO were retrospectively reviewed. Seventy-five patients (78.1%) were response and 21 (21.9%) were non-responsive to IVMP treatment. A higher TSH-R antibody (TRAb) and thyroid-stimulating antibody (TSAb) following treatment were associated with a high risk of no treatment response (P = 0.017; P = 0.047, respectively). TRAb and TSAb levels before treatment were significantly related to TRAb and TSAb levels after treatment (P < 0.001, respectively). The cut-off values for the prediction of poor treatment response of the TRAb and TSAb before and after treatment were 8.305 IU/L, 5.035 IU/L and 449.5%, 361%, respectively (P = 0.027, P =0.001 and P = 0.136, P = 0.004, respectively). Conclusion: It was observed that elevated levels of TRAb and TSAb prior to IVMP treatment were positively correlated with post-treatment levels of these antibodies. Furthermore, in cases of non-response to IVMP therapy, a diminished decline in both antibodies was observed, and elevated levels of TRAb and TSAb post-treatment were found to be a significant predictor of poor treatment outcome. Measurement of TRAb and TSAb throughout the course of treatment in moderate-to-severe and active cases of GO may offer valuable insights into treatment prognosis and aid in the decision-making process regarding the potential need for increased IVMP dosage or alternative therapeutic strategies.

Long-term surgical outcomes of basic-type exotropia in patients with hyperopia.

BACKGROUND: To investigate the surgical outcomes of basic-type exotropia in patients with hyperopia. METHODS: The medical records of patients who underwent surgery for basic-type exotropia and had been followed up for ≥ 2 years were retrospectively recruited. Patients with myopia and spherical equivalent (SE) < -1.0 diopters (D) were excluded. The patients were classified according to the SE: group H had a SE ≥ + 1.0 D, and group E had -1.0 ≤ SE < + 1.0 D. The surgical success rate and sensory outcome were compared. Surgical success was defined as exodeviation ≤ 10 prism diopters (PD) and esodeviation ≤ 5 PD at 6 m fixation. Stereoacuity was measured using the Titmus Preschool Stereoacuity Test. RESULTS: Seventy-five patients (24 males and 51 females, mean age 5.1 ± 2.6 years, range 2.7-14.8) were included. The SE ranged from -0.9 to 4.4 and 21 patients were classified into group H and 54 into group E. The success rates were higher in group H than in group E during the entire follow-up period, but the differences were significant only at the final examination. At the final follow-up, 11 of the 21 (52.4%) patients in group H and 15 of the 54 (27.7%) in group E maintained successful alignment, whereas 10 (47.6%) and 38 (70.4%) patients exhibited recurrence. Overcorrection was exhibited in one (1.9%) patient in group E. Sensory results were comparable between the groups. The follow-up period did not differ between the two groups. The survival analysis showed no difference in the surgical results between the two groups. CONCLUSIONS: Surgery for basic-type intermittent exotropia resulted in superior outcomes in patients with hyperopia compared to those with emmetropia.

Factors related to steroid treatment responsiveness in thyroid eye disease patients and application of SHAP for feature analysis with XGBoost.

Introduction: The primary treatment for active thyroid eye disease (TED) is immunosuppressive therapy with intravenous steroids. In this study, we attempted to predict responsiveness to steroid treatment in TED patients using eXtreme Gradient Boosting (XGBoost). Factors associated with steroid responsiveness were also statistically evaluated. Methods: Clinical characteristics and laboratory results of 89 patients with TED who received steroid treatment were retrospectively reviewed. XGBoost was used to explore responsiveness to steroid treatment, and the diagnostic performance was evaluated. Factors contributing to the model output were investigated using the SHapley Additive exPlanation (SHAP), and the treatment response was investigated statistically using SPSS software. Results: The eXtra Gradient Boost model showed high performance, with an excellent accuracy of 0.861. Thyroid-stimulating hormone, thyroid-stimulating immunoglobulin (TSI), and low-density lipoprotein (LDL) cholesterol had the highest impact on the model. Multivariate logistic regression analysis showed that less extraocular muscle limitation and high TSI levels were associated with a high risk of poor intravenous methylprednisolone treatment response. As a result of analysis through SHAP, TSH, TSI, and LDL had the highest impact on the XGBoost model. Conclusion: TSI, extraocular muscle limitation, and LDL cholesterol levels may be useful in predicting steroid treatment response in patients with TED. In terms of machine learning, XGBoost showed relatively robust and reliable results for small datasets. The machine-learning model can assist in decision-making for further treatment of patients with TED.

Successful Treatment of Optic Neuropathy Associated with Sphenoid Sinus Aspergillosis.

PURPOSE: We report a case of optic neuropathy related to sphenoid sinus aspergillosis which showed good visual recovery with surgery and medical antifungal treatment. METHODS: Observational case study Case Presentation A 62-year-old man presented with decreased visual acuity in the right eye for 3 weeks. His visual acuity was counting fingers in the right eye and 20/20 in the left eye. Relative afferent pupillary defects were detected in the right eye. Optic neuropathy related to invasive fungal sphenoid sinusitis was suspected via radiologic evaluation. Endoscopic sinus surgery was performed and histopathological examination revealed aspergillosis. Amphotericin B combined with ceftriaxone and metronidazole was started. After the fungal culture results were positive for the Aspergillus species, amphotericin B was changed to voriconazole. At 1 month after surgery, visual acuity improved to 20/25. CONCLUSION: Appropriate radiologic evaluation can be helpful when optic neuropathy associated with a fungal infection is suspected, and timely surgical and medial treatment should be considered.

Clinical Results According to Inferior Oblique Manipulation in Patients with Inferomedial Blowout Fracture Involving the Orbital Strut.

Background: Detachment of the inferior oblique muscle may be necessary under certain circumstances to repair a large inferomedial orbital fracture involving the orbital strut. This study aimed to evaluate the outcomes of patients who underwent surgeries with and without inferior oblique muscle reattachment after its detachment to repair the orbital wall fractures. Methods: Forty patients who underwent repair of combined floor and medial orbital wall fracture involving the orbital strut at a single tertiary institution between January 2014 and December 2020 were reviewed. Groups 1 and 2 comprised 20 patients each, who underwent surgery with inferior oblique muscle detachment without and with reattachment, respectively, and were followed up for at least 6 months postoperatively. Enophthalmos, Goldmann diplopia test, alignment test, ocular motility test, and orbital inferomedial angle ratio were the outcome measures. Results: Statistically significant improvement was observed in ocular motility, diplopia, and enophthalmos postoperatively at the 1- and 6-month follow-up (p < 0.01). The mean postoperative inferomedial angle ratio (102.28 ± 10.62%) was improved significantly compared with the preoperative inferomedial angle ratio (115.61 ± 4.38%) (p = 0.004) in all patients. After surgery, inferior oblique muscle underaction was observed in seven and six patients in groups 1 and 2, respectively, which was associated with preoperative extraocular movement limitation and strabismus. Two patients showed diplopia in both groups at the last follow-up; they had inferior oblique muscle underaction but no enophthalmos. Conclusion: Orbital fracture repair with or without inferior oblique muscle reattachment was clinically effective and safe; however, patients with preoperative strabismus and extraocular motility limitation should be informed of the increased risk of postoperative complications.

Binocular function in patients with intermittent exotropia accompanied by unilateral congenital ptosis.

Patients with intermittent exotropia (IXT) have a wide range of binocular deficits. This study aims to evaluate the effect of ptosis on the binocular function of patients with IXT. Clinical records of 45 IXT patients with congenital ptosis (IXT-ptosis group) and 58 age-matched IXT patients without ptosis (IXT only group) who presented for eye examination between January 2017 and June 2020 were retrospectively reviewed. Patients with amblyopia were excluded to rule out the effects of visual acuity on binocularity. Best-corrected visual acuity (BCVA), the magnitude of exodeviation at distance and at near, stereopsis, and office-based control scores at the first visit were reviewed. The binocular functions of the two groups were compared. The mean ± SD age of the overall patients was 6.6 ± 2.7 years. There were no significant differences in the distribution of age, sex, spherical equivalent refraction, or BCVA between the two groups (all p > 0.05). Although the office-based control scores at distance and near were slightly worse in the IXT-ptosis group, the differences were not statistically significant (at distance, 2.8 ± 1.87 vs. 2.2 ± 1.13, p = 0.08; at near, 1.8 ± 0.67 vs. 1.6 ± 0.74, p = 0.11). Furthermore, the IXT-ptosis group had worse stereopsis at distance (p = 0.01). There were no significant differences between the two groups in near stereopsis or exodeviation magnitude (p > 0.05). A larger proportion of patients had suppression on the Bagolini test in the IXT-ptosis group than in the IXT-only group (p = 0.04). The IXT-ptosis group had worse distance stereoacuity, and a larger proportion of patients had suppression on the Bagolini test than the IXT only group. In IXT patients, the presence of coexisting ptosis can have a further deleterious impact on binocular function.

Endonasal Endoscopic Removal of Orbital Cavernous Venous Malformation With Optic Neuropathy.

Several surgical methods have been employed, but the management of orbital cavernous venous malformations at the orbital apex remains challenging. The authors present an endonasal endoscopy-assisted removal of an orbital apex cavernous venous malformation compressing the optic nerve with the addition of an inferomedial conjunctival approach. A 43-year-old Asian man presented with an orbital cavernous venous malformation incidentally found radiographically with a history of decreased vision of 20/50 oculus dexter (OD). The patient's visual field index was 22%, with signs of optic neuropathy. An endonasal endoscopic procedure combining transconjunctival and caruncular orbitotomies was adopted because of its deep posterior placement inside the orbit. The cavernous venous malformation was removed without complications, and the visual function of the patients recovered. For these challenging lesions, an endonasal endoscopic technique with an anterior orbitotomy may be a promising alternative. Simple packing material may adequately repair the medial orbital wall; there were no complications during the 12-month follow-up period.

Comparison of vision-related quality of life in patients with homonymous hemianopia and monocular blindness.

To evaluate the vision-related quality of life (QoL) in patients with homonymous hemianopia (HH). The study compared the QoL in 32 patients with HH and 33 patients with monocular blindness. Best-corrected visual acuity (BCVA) and visual field test were investigated. The National Eye Institute-Visual Function Questionnaire 25 (NEI VFQ-25) and independent mobility questionnaires (IMQs) were used to assess their perceived visual and physical functioning abilities. The results of QoL questionnaires were compared in two groups. The mean deviation (MD) in the better eye was significantly lower in the HH group than in the monocular blindness group. The composite scores of NEI-VFQ and IMQs were significantly lower in the HH patients than in the monocular blindness patients. The driving-related score was significantly lower in patients with right hemianopsia than in those with left hemianopsia. The outdoor activity-related score was significantly lower in patients aged less than 55 years than in patients aged 55 years and more. Homonymous hemianopia had a negative impact on patients' QoL by limiting their vision related activities compared to monocular blindness. The MD of the better eye in the HH patients reflects the binocular visual field and can affect the real visual function and QoL.

Predictive value of OCT and MRI for postoperative visual recovery in patients with chiasmal compressive lesions.

PURPOSE: We aimed to investigate the predictive value of retinal thickness measured by optical coherence tomography (OCT) and mass biometrics measured using magnetic resonance image (MRI) for visual recovery after surgery for removal of a mass compressing the optic chiasm. METHODS: Consecutive patients who showed typical temporal visual field defect (VFD) with respect to the vertical meridian due to a chiasmal compressive mass and who underwent mass removal surgery were recruited. Ophthalmic examination was performed preoperatively and postoperatively. Retinal thickness was measured by the Cirrus OCT. The height and size of the mass and suprasellar extension (SSE) in both the sagittal and coronal planes were evaluated. Patients were divided into two groups based on the improvement in VFD (mean deviation [MD] change ≥ 5 dB: group R; others: group NR) and clinical characteristics were compared. RESULTS: Fifteen patients were included in the study. Eight (53.3%) patients were allocated into group R and others (7 patients, 46.7%) into group NR. Age, sex, initial visual acuity, initial MD was not different between the two groups. The retinal thicknesses were not different while tumor height, volume, and both sagittal and coronal SSE were significantly different between the two groups. (p = 0.029, 0.014, <0.001, and <0.001, respectively) All MRI parameters showed significant predictive value for the degree of MD recovery. CONCLUSION: MRI showed better predictive value than OCT in predicting postoperative VFD recovery in patients with temporal VFDs due to chiasmal compressive disorder.

Clinical Characteristics for Predicting Recovery of Acquired Fourth Cranial Nerve Palsy.

BACKGROUND: Fourth cranial nerve palsy is the most common disease diagnosed in patients with vertical diplopia. Although it is reported to present a good prognosis, there are currently no agreed on prognostic factors that anticipate the recovery of the palsy other than the etiology. The purpose of this study was to investigate the prognostic factors of acquired fourth cranial nerve palsy. METHODS: The medical records of consecutive patients diagnosed with acquired unilateral fourth cranial nerve palsy from 2010 to 2020 and followed up for ≥6 months were retrospectively reviewed. The cause and degree of palsy, ocular deviation (horizontal, vertical, and cyclo), and fundus torsion were reviewed. The cause of palsy was classified as ischemic, traumatic, intracranial mass, others, or idiopathic. Patients were divided into 2 groups according to palsy recovery: complete recovery (group CR) or not CR (group NCR). The clinical characteristics of the 2 groups were compared, and the risk factors for incomplete recovery were investigated. RESULTS: Thirty-five patients (25 men) were included in the study. The average age was 55.94 ± 16.11 years. CR was achieved in 23 patients (65.7%), and the time to recovery was 3.91 ± 4.03 months. The most common cause was traumatic (40.0%), followed by ischemia (37.1%), intracranial mass (11.4%), others (8.6%), and idiopathic (2.9%). The degree of palsy and fundus torsion was significantly higher in group NCR (P = 0.010 and P = 0.001). Severe oculomotor limitation, large fundus torsion, and intracranial mass cause rather than ischemic cause indicated a higher risk of incomplete or no recovery (P = 0.016, P = 0.009, and P = 0.043). CONCLUSION: Identifying whether a patient has an intracranial mass, severe oculomotor limitation, or large fundus excyclotorsion may be useful for predicting the recovery of acquired unilateral fourth cranial nerve palsy.

Establishment of a prediction tool for ocular trauma patients with machine learning algorithm.

AIM: To predict final visual acuity and analyze significant factors influencing open globe injury prognosis. METHODS: Prediction models were built using a supervised classification algorithm from Microsoft Azure Machine Learning Studio. The best algorithm was selected to analyze the predicted final visual acuity. We retrospectively reviewed the data of 171 patients with open globe injury who visited the Pusan National University Hospital between January 2010 and July 2020. We then applied cross-validation, the permutation feature importance method, and the synthetic minority over-sampling technique to enhance tool performance. RESULTS: The two-class boosted decision tree model showed the best predictive performance. The accuracy, precision, recall, F1 score, and area under the receiver operating characteristic curve were 0.925, 0.962, 0.833, 0.893, and 0.971, respectively. To increase the efficiency and efficacy of the prognostic tool, the top 14 features were finally selected using the permutation feature importance method: (listed in the order of importance) retinal detachment, location of laceration, initial visual acuity, iris damage, surgeon, past history, size of the scleral laceration, vitreous hemorrhage, trauma characteristics, age, corneal injury, primary diagnosis, wound location, and lid laceration. CONCLUSION: Here we devise a highly accurate model to predict the final visual acuity of patients with open globe injury. This tool is useful and easily accessible to doctors and patients, reducing the socioeconomic burden. With further multicenter verification using larger datasets and external validation, we expect this model to become useful worldwide.

An office-based fix-and-follow grading system assessing visual function in preverbal children.

BACKGROUND: Assessing visual function in infants is usually challenging. Fix-and-Follow is a simple and popular method for assessing early development of visual perception in infants, currently however, there is no formal reproducible method for grading the capacity of fix-and-follow. This study was to develop and validate a new fix-and-follow grading system for assessing visual function development in preverbal children. METHODS: In this cross-sectional study, the fix-and-follow grades was evaluated in 21 consecutive preverbal children. Fixation was categorised as grade 1 if there was no response to the target and grade 2 if there was a response but only for < 3 s. Grades of 3 and 4 were assigned based capacities to (1) fix on a moving target for ≥3 s, and (2) shift fixation from one target to another. If only one of these two criteria was met, grade 3 was assigned. If both were met, grade 4 was assigned. Following was evaluated using smooth pursuit movement, where grade 1 indicated no movement, grade 2 partial movement, and grade 3 complete movement. Two ophthalmologists independently applied the grading method in all patients. Then one of two examiners repeated the examinations to investigate the intra-observer agreement of the grading system. RESULTS: Intra-observer agreement was excellent (Kappa coefficient = 0.823) and inter-observer agreement was good (Kappa coefficient = 0.625). All patients who exhibited abnormal ocular movement had score discrepancy between a new fix-and-following grading examination. CONCLUSIONS: The new fix-and-follow grading scale can be applied easily in preverbal children in an office setting, and it proved reliable and reproducible.

An Overview of the Korean Intermittent Exotropia Multicenter Study by the Korean Association for Pediatric Ophthalmology and Strabismus.

The Korean Intermittent Exotropia Multicenter Study (KIEMS), which was initiated by the Korean Association of Pediatric Ophthalmology and Strabismus, is a collaborative multicenter study on intermittent exotropia in Korea. The KIEMS was designed to provide comprehensive information, including subjective and objective findings of intermittent exotropia in a large study population. A total of 65 strabismus specialists in 53 institutions contributed to this study, which, to date, is one of the largest clinical studies on intermittent exotropia. In this article, we provide a detailed methodology of the KIEMS to help future investigations that may use the KIEMS data.

Diagnostic yield of targeted next-generation sequencing in infantile nystagmus syndrome.

Background: Infantile nystagmus syndrome (INS) is a genetically heterogeneous disorder. Identifying genetic causes of INS would help clinicians to facilitate clinical diagnosis and provide appropriate treatment. The aim of this study was to determine the diagnostic utility of targeted next-generation sequencing (NGS) for INS.Materials and methods: We recruited 37 patients who were referred to the Neuro-ophthalmology clinics for evaluations of INS. NGS was performed using a targeted panel that included 98 candidate genes associated with INS. We identified pathogenic variants according to guidelines of the American College of Medical Genetics and Genomics. We also calculated the sensitivity and specificity of each clinical sign to assess the diagnostic yield of our gene panel.Results: After variant filtering, annotation, and interpretation, the potential pathogenic variants were detected in 13 of the 37 patients, achieving a molecular diagnostic rate of 35%. The identified genes were PAX6 (n = 4), FRMD7 (n = 4), GPR143 (n = 2), CACNA1F (n = 1), CNGA3 (n = 1) and GUCY2D (n = 1). In approximately 30% (n = 4) of the patients, the initial clinical diagnosis was revised after a molecular diagnosis was performed. The presence of a family history had the highest predictive power for a molecular diagnosis (sensitivity = 61.5%, specificity = 91.7%), and the sensitivity increased when the family history was considered together with one of two clinical signs such as pendular nystagmus waveforms or anterior segment dysgenesis.Conclusions: Our study shows that targeted NGS can be useful to determine a molecular diagnosis for patients with INS. Targeted NGS also helps to confirm a clinical diagnosis in atypical phenotypes or unresolved cases.