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Abstract Background Human papillomavirus (HPV) has been detected in eyelid sebaceous gland carcinoma (SGC) and squamous cell carcinoma (SCC), and detection rates greatly varied across studies. This study aimed to investigate the presence of HPV in eyelid SGC and SCC among Koreans and its correlation with clinicopathological characteristics. Methods Surgically resected eyelid samples diagnosed as SGC or SCC from January 1999 to June 2011 were identified from the pathology database of three referral centres in Korea. Clinicopathological information including origin (skin vs. tarsal conjunctiva) and treatment outcomes were retrospectively reviewed. Immunohistochemistry (IHC) for p16, HPV DNA in situ hybridisation (ISH), and polymerase chain reaction-based DNA microarray were performed in paraffin-embedded tissue sections. Results Our cohort included 34 SGC and 12 SCC cases with Asian ethnicity. HPV was detected in 4 SGC and 6 SCC by DNA microarray, while 2 SCC (16.7%) showed positivity in ISH. SCC of tarsal conjunctival origin was significantly more common in HPV-positive SCC than in HPV-negative SCC (5 of 6 vs. 0 of 6, P = 0.015, Fisher’s exact test). Among samples showing positive staining in p16 IHC, HPV positivity rates were 0.0% (0/19) in SGC and 100% (3/3) in SCC. There was no significant difference in overall and local recurrence rate in eyelid SGC and SCC according to the HPV status (P > 0.99). Conclusions HPV was found in a subset of eyelid SGC and SCC among Koreans and might be aetiologically related to SCC of tarsal conjunctival origin. Overexpression of p16 is considered to be inappropriate as an indicator of HPV infection in eyelid SGC. Further investigation is required to elucidate the transmission route and pathogenic roles of HPV.

Abstract Artificial intelligence as a screening tool for eyelid lesions will be helpful for early diagnosis of eyelid malignancies and proper decision-making. This study aimed to evaluate the performance of a deep learning model in differentiating eyelid lesions using clinical eyelid photographs in comparison with human ophthalmologists. We included 4954 photographs from 928 patients in this retrospective cross-sectional study. Images were classified into three categories: malignant lesion, benign lesion, and no lesion. Two pre-trained convolutional neural network (CNN) models, DenseNet-161 and EfficientNetV2-M architectures, were fine-tuned to classify images into three or two (malignant versus benign) categories. For a ternary classification, the mean diagnostic accuracies of the CNNs were 82.1% and 83.0% using DenseNet-161 and EfficientNetV2-M, respectively, which were inferior to those of the nine clinicians (87.0–89.5%). For the binary classification, the mean accuracies were 87.5% and 92.5% using DenseNet-161 and EfficientNetV2-M models, which was similar to that of the clinicians (85.8–90.0%). The mean AUC of the two CNN models was 0.908 and 0.950, respectively. Gradient-weighted class activation map successfully highlighted the eyelid tumors on clinical photographs. Deep learning models showed a promising performance in discriminating malignant versus benign eyelid lesions on clinical photographs, reaching the level of human observers.

Abstract The aim of this study is to characterize the microRNA (miRNA) expression signatures in patients with thyroid eye disease (TED) and identify miRNA biomarkers of disease activity. Total RNA was isolated from the sera of patients with TED (n = 10) and healthy controls (HCs, n = 5) using the miRNeasy Serum/Plasma Kit. The NanoString assay was used for the comprehensive analysis of 798 miRNA expression profiles. Analysis of specific miRNA signatures, mRNA target pathway analysis, and network analysis were performed. Patients with TED were divided into two groups according to disease activity: active and inactive TED groups. Differentially expressed circulating miRNAs were identified and tested using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) tests in the validation cohort. Among the 798 miRNAs analyzed, 173 differentially downregulated miRNAs were identified in TED patients compared to those in the HCs. Ten circulating miRNAs were differentially expressed between the active and inactive TED groups and regarded as candidate biomarkers for TED activity (one upregulated miRNA: miR-29c-3p; nine downregulated miRNAs: miR-4286, miR-941, miR-571, miR-129-2-3p, miR-484, miR-192-5p, miR-502-3p, miR-597-5p, and miR-296-3p). In the validation cohort, miR-484 and miR-192-5p showed significantly lower expression in the active TED group than in the inactive TED group. In conclusion, the expression levels of miR-484 and miR-192-5p differed significantly between the active and inactive TED groups, suggesting that these miRNAs could serve as circulating biomarkers of TED activity, however, these findings need to be validated in further studies.

The escalating utilization of plastics in daily life has resulted in pervasive environmental pollution and consequent health hazards. The challenge of detecting and capturing microplastics, which are imperceptible to the naked eye, is exacerbated by their diminutive size, hydrophobic surface properties, and capacity to absorb organic compounds. This study focuses on the application of peptides, constituted of specific amino acid sequences, and microneedles for the rapid and selective identification of microplastics. Peptides, due to their smaller size and greater environmental stability compared with antibodies, emerge as a potent solution to overcome the limitations inherent in existing detection methodologies. To immobilize peptides onto microneedles, this study employed microneedles embedded with gold nanorods, augmenting them with sulfhydryl (SH) groups at the peptides’ termini. The sensor developed through this methodology exhibited efficient peptide binding to the microneedle tips, thereby facilitating the capture of microplastics. Raman spectroscopy was employed for the detection of microplastics, with the results demonstrating successful attachment to the microneedles. This novel approach not only facilitates localized analysis but also presents a viable strategy for the detection of microplastics across diverse environmental settings.

Abstract Although the clinical activity score (CAS) is a validated scoring system for identifying disease activity of thyroid-associated orbitopathy (TAO), it may produce differing results depending on the evaluator, and an experienced ophthalmologist is required for accurate evaluation. In this study, we developed a machine learning (ML)-assisted system to mimic an expert’s CAS assessment using digital facial images and evaluated its accuracy for predicting the CAS and diagnosing active TAO (CAS ≥ 3). An ML-assisted system was designed to assess five CAS components related to inflammatory signs (redness of the eyelids, redness of the conjunctiva, swelling of the eyelids, inflammation of the caruncle and/or plica, and conjunctival edema) in patients’ facial images and to predict the CAS by considering two components of subjective symptoms (spontaneous retrobulbar pain and pain on gaze). To train and test the system, 3,060 cropped images from 1020 digital facial images of TAO patients were used. The reference CAS for each image was scored by three ophthalmologists, each with > 15 years of clinical experience. We repeated the experiments for 30 randomly split training and test sets at a ratio of 8:2. The sensitivity and specificity of the ML-assisted system for diagnosing active TAO were 72.7% and 83.2% in the test set constructed from the entire dataset. For the test set constructed from the dataset with consistent results for the three ophthalmologists, the sensitivity and specificity for diagnosing active TAO were 88.1% and 86.9%. In the test sets from the entire dataset and from the dataset with consistent results, 40.0% and 49.9% of the predicted CAS values were the same as the reference CAS, respectively. The system predicted the CAS within 1 point of the reference CAS in 84.6% and 89.0% of cases when tested using the entire dataset and in the dataset with consistent results, respectively. An ML-assisted system estimated the clinical activity of TAO and detect inflammatory active TAO with reasonable accuracy. The accuracy could be improved further by obtaining more data. This ML-assisted system can help evaluate the disease activity consistently as well as accurately and enable the early diagnosis and timely treatment of active TAO.

The retinal structural changes after subretinal implantation of three-dimensional (3D) microelectrodes were investigated in a mini pig. Three types of electrode were implanted into the subretinal spaces of nine mini pigs: 75-μm-high 3D electrodes on a 200-μm-thick right-angled polydimethylsiloxane (PDMS) substrate (group 1); a 140-μm-thick sloped PDMS substrate without electrodes (group 2); and a 140-μm-thick sloped PDMS substrate with 20-μm-high 3D electrodes (group 3). One mini pig was used as a control. Spectral domain–optical coherence tomography (SD–OCT) images were obtained at baseline and 2, 6, and 12 weeks post-surgery. Retinal specimens were immunostained using a tissue-clearing method 3 months post-implantation. The 75-μm-high 3D electrodes progressively penetrated the inner nuclear layer (INL) and touched the inner plexiform layer (IPL) 2 weeks post-surgery. At 6 weeks post-operatively, the electrodes were in contact with the nerve-fiber layer, accompanied by a severe fibrous reaction. In the other groups, the implants remained in place without subretinal migration. Immunostaining showed that retinal ganglion and bipolar cells were preserved without fibrosis over the retinal implants in groups 2 and 3 during the 12-week implantation period. In summary, SD–OCT and immunohistology results showed differences in the extent of reactions, such as fibrosis over the implants and penetration of the electrodes into the inner retinal layer depending on different types of electrodes. A sloped substrate performed better than a right-angled substrate in terms of retinal preservation over the implanted electrodes. The 20-μm-high electrodes showed better structural compatibility than the 75-μm-high 3D electrodes. There was no significant difference between the results of sloped implants without electrodes and 20-μm-high 3D electrodes, indicating that the latter had no adverse effects on retinal tissue.

With the advancement of the Internet of Things (IoT), numerous electronic devices are connected to each other and exchange a vast amount of data via the Internet. As the number of connected devices increases, security concerns have become more significant. As one of the potential solutions for security issues, hardware intrinsic physical unclonable functions (PUFs) are emerging semiconductor devices that exploit inherent randomness generated during the manufacturing process. The unclonable security key generated from PUF can address the inherent limitations of conventional electronic systems which depend solely on software. Although numerous PUFs based on the emerging memory devices requiring switching operations have been proposed, achieving hardware intrinsic PUF with low power consumption remains a key challenge. Here, we demonstrate that the process-induced nonlinear conductance variations of oxide semiconductor-based Schottky diodes provide a suitable source of entropy for the implementation of PUF without switching operation. Using a mild oxygen plasma treatment, the surface electron accumulation layer that forms naturally in oxide semiconductor film can be partially eliminated, resulting in a large variation of nonlinearity as an exotic entropy source. The mild plasma-treated Schottky diodes showed near ideal 50% average uniformity and uniqueness, as well as an ideal entropy value without the need for additional hardware area and power costs. These findings will pave the way for the development of hardware intrinsic PUFs to realize energy-efficient cryptographic hardware.

Purpose To quantitatively analyze morphological and functional alterations of the meibomian glands in eyes with marginal entropion and their changes after surgery. Methods Sixty eyes of 52 patients with marginal entropion and underwent meibography and interferometer were included. One-hundred and seventeen age- and sex-matched eyes with minimal to mild meibomian gland dysfunction (MGD) were recruited as control eyes. Meibomian gland loss (MGL) and lipid layer thickness (LLT) were compared between eyes with marginal entropion and control eyes. Subgroup analysis was performed according to the extent of entropion. MGL and average LLT at 1 and 5 months after surgery were compared with those of 20 eyes with marginal entropion followed without surgery. Results In eyes with marginal entropion, MGL was higher (27.7% vs. 12.8%, P = 0.014), and average LLT was thinner (64 nm vs. 86 nm, P = 0.005) than those in control eyes. MGL was higher in eyes with more extensive entropion (> 2/3 eyelid width) than in eyes with less extensive entropion (≤ 1/3 eyelid width) (40.5% vs. 13.2%, P = 0.001). Average LLT increased after surgery (97 nm at 1 month, P = 0.003; 75 nm at 5 months, P = 0.319), and thicker than that of eyes followed without surgery (97 nm vs. 66 nm, P = 0.046). MGLs after surgery remained unchanged from the preoperative MGL (all P > 0.7). Conclusion Marginal entropion is associated with morphological and functional alterations of the meibomian glands. Functional improvement after entropion repair suggests that marginal entropion could cause or exacerbate MGD. Further studies are required to establish the role of entropion repair in managing MGD.

PurposeTo investigate the association between the bony nasolacrimal duct (NLD) size and outcomes of nasolacrimal silicone intubation for incomplete primary acquired nasolacrimal duct obstruction (PANDO).MethodsPatients who underwent silicone intubation for incomplete PANDO and had undergone facial computed tomography (CT) were included. Surgical success was judged by both epiphora improvement and normalized tear meniscus height (TMH; < 300 μm) on anterior segment optical coherence tomography at 3 months after tube removal. The area, major axis diameter, and minor axis diameter of the elliptic bony NLD sections were measured in 1.0 mm-thick axial CT images. These bony NLD sizes were analyzed for associations with surgical success and TMH normalization.ResultsEighty-one eyes of 48 patients were investigated. The smallest area and the smallest minor axis diameter were significantly larger in the success group (49 eyes), compared with those in the failure group (median smallest minor axis diameter: 4.7 mm vs. 3.8 mm, P = 0.008, Mann-Whitney U test). There was also a tendency for the TMH normalization rate to significantly increase as the smallest area and the smallest minor axis diameter increased (P = 0.028 and 0.037, respectively, Fisher's 2 × 4 tests). Under multivariable logistic regression analysis using generalized estimating equation, a larger smallest minor axis diameter was associated with success of the nasolacrimal silicone intubation (odds ratio: 2.481, 95% confidence interval: 1.143-5.384).ConclusionSurgical success of the nasolacrimal silicone intubation in incomplete PANDO is associated with a larger smallest minor axis diameter of the bony NLD. This finding will help understand the pathophysiology of surgical failure after nasolacrimal silicone intubation.

Abstract Background Trastuzumab emtansine (Kadcyla®, T-DM1) is an antibody-drug conjugate used to treat HER2 (human epidermal growth factor receptor 2) overexpressing metastatic breast cancer. In this report, we present the first case of lacrimal drainage system stenosis identified after T-DM1 administration, and its successful treatment with a topical steroid. Case presentation A 36-year-old female with metastatic breast cancer was referred for excessive tearing of both eyes. She previously underwent mastectomy and was treated with multiple anti-cancer regimens. However, metastases to liver and bone were identified and T-DM1 was administered. After 2 months, epiphora developed in both eyes and the patient was referred for ophthalmologic examination. The height of the tear meniscus was increased. The fluorescein dye disappearance test (FDDT) showed a delayed clearance in both eyes. Diagnostic lacrimal probing demonstrated a lower distal canalicular stenosis in both eyes. Dacryocystography indicated multiple focal narrowing of nasolacrimal duct in the right eye and diffused narrowing of nasolacrimal duct in the left eye. Topical eyedrop of tobramycin 0.3% and dexamethasone 0.1% were prescribed four times a day. After 2 months of treatment, the patient reported relief from epiphora, and the height of tear meniscus was normalized in both eyes. Conclusion T-DM1 administration in breast cancer treatment can induce lacrimal drainage system stenosis, which can be treated effectively with a topical steroid.

Abstract Background To elucidate the clinical features of strabismus associated with IgG4-related ophthalmic disease (IgG4-ROD). Case summary All of the four patients with IgG4-ROD showed marked enlargement of the extraocular muscles, however, two patients showed orthotropia with full ductions and versions. One patient showed a small angle of exotropia and hypertropia of less than 5 prism diopters. One remaining patient showed orthotropia, full ductions and versions despite marked enlargement of the extraocular muscles, then developed hypertropia up to 35 prism diopters with activation of inflammation, which promptly improved after treatment with oral steroids. Conclusions IgG4-ROD usually shows normal ocular motility despite extraocular muscle enlargement, which is the key distinguishing feature from other orbital inflammatory diseases. Active flare-up with increased serum IgG4 levels may produce a large angle of eye deviation, but mostly respond well to steroid treatment.

The biological behavior of sebaceous carcinoma (SeC) is relatively indolent; however, local invasion or distant metastasis is sometimes reported. Nevertheless, a lack of understanding of the genetic background of SeC makes it difficult to apply effective systemic therapy. This study was designed to investigate major genetic alterations in SeCs in Korean patients. A total of 29 samples, including 20 ocular SeCs (SeC-Os) and 9 extraocular SeCs (SeC-EOs), were examined. Targeted next-generation sequencing tests including 171 cancer-related genes were performed. TP53 and PIK3CA genes were frequently mutated in both SeC-Os and SeC-EOs with slight predominance in SeC-Os, whereas the NOTCH1 gene was more commonly mutated in SeC-EOs. In clinical correlation, mutations in RUNX1 and ATM were associated with development of distant metastases, and alterations in MSH6 and BRCA1 were associated with inferior progression-free survival (all p < 0.05). In conclusion, our study revealed distinct genetic alterations between SeC-Os and SeC-EOs and some important prognostic molecular markers. Mutations in potentially actionable genes, including EGFR, ERBB2, and mismatch repair genes, were noted, suggesting consideration of a clinical trial in intractable cases.

PurposeTo investigate longitudinal changes in risk factors for amblyopia in children treated with congenital nasolacrimal duct obstruction (CNLDO).MethodsRetrospective observational case control study. A total of 446 children under 4 years of age who underwent probing and/or intubation for CNLDO between January 2004 and January 2018, and 446 age-matched controls were included. Cycloplegic refraction and ocular alignment were investigated at the time of treatment and after at least one year of symptom improvement. Children were classified as having amblyopia risk factors on the basis of the American Association for Pediatric Ophthalmology and Strabismus guideline in 2013.Main outcome measuresThe prevalence of amblyogenic refractive errors, and determinants associated with the presence of amblyogenic refractive errors in CNLDO patients.ResultsThe prevalence of amblyogenic refractive errors in CNLDO patients (5.4%) was similar to that of the control group (6.5%) (P = 0.571). After one year of symptom improvement in CNLDO patients, the prevalence of amblyogenic refractive errors was 4.7%. There was no difference in the prevalence of amblyogenic refractive errors between unilateral and bilateral CNLDO patients. Multivariate analysis revealed that manifest strabismus was the only risk factor related with the presence of amblyogenic refractive errors (odds ratio = 6.383, confidence interval = 1.205-33.826, P = 0.029).ConclusionsThis study found no evidence to suggest that the prevalence of amblyopia risk factors is higher in CNLDO patients compared with normal controls. Manifest strabismus was the only determinant associated with the presence of amblyogenic refractive errors.

This study presents the fabrication of three-dimensional (3D) microelectrodes for subretinal stimulation, to accommodate adjacent return electrodes surrounding a stimulating electrode. For retinal prosthetic devices, the arrangement of return electrodes, the electrode size and spacing should be considered together, to reduce the undesired dissipation of electric currents. Here, we applied the hexagonal arrangement to the microelectrode array for the localized activation of retinal cells and better visual acuity. To provide stimuli more efficiently to non-spiking neurons, a 3D structure was created through a customized pressing process, utilizing the elastic property of the materials used in the fabrication processes. The diameter and pitch of the Pt-coated electrodes were 150 μm and 350 μm, respectively, and the height of the protruded electrodes was around 20 μm. The array consisted of 98 hexagonally arranged electrodes, supported by a flexible and transparent polydimethylsiloxane (PDMS) base, with a thickness of 140 μm. Also, the array was coated with 2 μm-thick parylene-C, except the active electrode sites, for more focused stimulation. Finally, the electrochemical properties of the fabricated microelectrodes were characterized, resulting in the mean impedance of 384.87 kΩ at 1 kHz and the charge storage capacity (CSC) of 2.83 mC·cm−2. The fabricated microelectrodes are to be combined with an integrated circuit (IC) for additional in vitro and in vivo experiments.

Objective: To elucidate the clinical features of ocular motility and the risk factors for recurrence in idiopathic orbital myositis. Methods: The medical records of 31 patients diagnosed with idiopathic orbital inflammation between 2003 and 2019 were retrospectively reviewed. All patients were initially treated with corticosteroids. Treatment outcome and ocular motility were noted. Results: Twenty-six patients (84%) had unilateral involvement and five patients (16%) were bilateral. Of the 31 patients, 22 patients (71%) showed ocular motility limitation. The mean grading scale of extraocular muscle (EOM) limitation was −1.65 ± 1.80. EOM limitation was found in the same direction of the most affected muscle in 14 patients (64%), while 8 patients (36%) showed duction limitation in the opposite direction. Nine patients (35%) suffered from recurrence. Recurrence was more likely to occur in patients with multiple muscle involvement (p < 0.001). The interval to relapse of symptoms after discontinuation of steroids was significantly shorter in patients with multiple recurrences compared to those with a single recurrence (1.8 ± 0.8 weeks versus 6.0 ± 1.4 weeks, p = 0.020). Conclusions: Idiopathic orbital myositis showed variable degrees of ocular motility limitation, and limitation in the same direction of the action of the affected muscle was more frequent. Recurrent myositis was more likely to have multiple muscle involvement. Rapid relapse of symptoms after discontinuation of steroids was a significant indicator of multiple recurrences.

To investigate the factors affecting recovery of diplopia and limited ocular motility in pediatric patients who underwent surgery for orbital wall fracture.Retrospective observational case series.In this retrospective observational case series, 150 pediatric patients (1-18 years old) who were diagnosed with orbital medial wall or floor fracture and underwent corrective surgery between 2004 and 2016 at Seoul National University Bundang Hospital were included. The medical records of patients with orbital medial wall or floor fracture were reviewed, including sex, age, diplopia, ocular motility, preoperative computed tomographic finding, and surgical outcomes. Factors affecting recovery of diplopia and ocular motility limitation were analyzed.Of the 150 patients (134 boys; mean age, 14.4 years) who underwent corrective surgery for orbital wall fracture, preoperative binocular diplopia was found in 76 (50.7%) patients and limited ocular motility in 81 (54.0%). Presence of muscle incarceration or severe supraduction limitation delayed the recovery of diplopia. In case of ocular motility limitation, presence of muscle incarceration and retrobulbar hemorrhage were related with the delayed resolution. Multivariate analysis revealed supraduction limitation (Hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.19-2.55), larger horizontal orbital floor defects (HR = 1.22, 95% CI = 1.07-1.38), and shorter time interval to first visit (HR = 0.73) as negative prognostic factors for the recovery of diplopia. In addition, muscle incarceration (HR = 3.53, 95% CI = 1.54-8.07) and retrobulbar hemorrhage (HR = 3.77, 95% CI = 1.45-9.82) were found as negative prognostic factors for the recovery of motility limitation.Presence of muscle incarceration and retrobulbar hemorrhage, horizontal length of floor fracture, supraduction limitation, and time interval from trauma to first visit were correlated with the surgical outcomes in pediatric orbital wall fracture patients. These results strengthen that the soft tissue damage associated with bony fracture affects the orbital functional unit. When managing children with orbital wall fracture, meticulous physical examination and thorough preoperative computed tomography based evaluation will help physicians to identify damage of orbital functional unit.

This study aims to analyze clinical and pathological characteristics of ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL) accompanying IgG4-positive cells. Fifty patients with a diagnosis of primary non-conjunctival ocular adnexal EMZL were enrolled in this study. The number of IgG4-positive cells and the ratio of IgG/IgG4 were evaluated by immunohistochemistry in the biopsy specimens. The patients were divided into two groups based on the absolute number and the ratio of IgG4-positive cells (IgG4-posivite vs IgG4-negative groups). The demographic data, clinical staging at diagnosis, histopathological characteristics, and response to initial treatment were comparatively analyzed between the 2 groups. Five (10%) of 50 patients were defined as IgG4-positive group, and all the cases showed characteristic histological features such as extensive plasma cell infiltration and dense fibrosis. Most of these patients (4 of 5 patients) had lymphoma of the lacrimal gland. The patients from the IgG4-positive group showed a lower response rate to initial treatment (87.5 vs 33%, p = 0.03) than IgG4-negative group with a median follow-up period of 38 months. A part of the ocular adnexal EMZLs were accompanied with IgG4-positive cells. Significantly, most IgG4-positive ocular adnexal EMZLs occurred in the lacrimal gland, and can be related with a more frequent treatment failure.

Background Down-sloping sensorineural hearing loss (SNHL) in people in their teens and 20s hampers efficient learning and communication and in-depth social interactions. Nonetheless, its aetiology remains largely unclear, with the exception of some potential causative genes, none of which stands out especially in people in their teens and 20s. Here, we examined the role and genotype–phenotype correlation of lipoxygenase homology domain 1 (LOXHD1) in down-sloping SNHL through a cohort study. Methods Based on the Seoul National University Bundang Hospital (SNUBH) genetic deafness cohort, in which the patients show varying degrees of deafness and different onset ages (n=1055), we have established the ’SNUBH Teenager–Young Adult Down-sloping SNHL’ cohort (10–35 years old) (n=47), all of whom underwent exome sequencing. Three-dimensional molecular modelling, minigene splicing assay and short tandem repeat marker genotyping were performed, and medical records were reviewed. Results LOXHD1 accounted for 33.3% of all genetically diagnosed cases of down-sloping SNHL (n=18) and 12.8% of cases in the whole down-sloping SNHL cohort (n=47) of young adults. We identified a potential common founder allele, as well as an interesting genotype–phenotype correlation. We also showed that transcript 6 is necessary and probably sufficient for normal hearing. Conclusions LOXHD1 exceeds other genes in its contribution to down-sloping SNHL in young adults, rising as a signature causative gene, and shows a potential but interesting genotype–phenotype correlation. [ABSTRACT FROM AUTHOR]

Background/Aims To report the long-term outcomes of enucleation and insertion of porous polyethylene (PP) orbital implant according to the evolving surgical techniques and implant in patients with paediatric retinoblastoma. Methods Patients with paediatric retinoblastoma who underwent enucleation and PP implant insertion from December 1998 to December 2014 were retrospectively reviewed and divided into four groups: group A, classic enucleation +PP implant; group B, enucleation +PP implant +anterior closure of the posterior Tenon's (ACPT) capsule; group C, enucleation +PP implant +free orbital fat graft +ACPT and group D, enucleation +smooth surface tunnel PP implant +ACPT. Survival analysis of implant exposure and eyelid malpositions was performed. Results One hundred and ninety-eight eyes of 196 patients were included. The median follow-up period was 13.0 years (range, 5.0-21.1). A 20 mm implant was inserted for 149 eyes (75.3%). The 10-year exposure-free survival probabilities were 44.6% in group A, 96.4% in group B, 97.4% in group C and 97.7% in group D. ACPT was associated with significant reduction in implant exposure (p<0.001). The most common eyelid malposition was upper eyelid ptosis (24.2%). The eyelid malposition-free survival probability did not differ among the four groups. However, the insertion of a 20 mm implant was associated with significant reduction in upper eyelid ptosis and lower eyelid entropion (p=0.004 and 0.038, respectively). Conclusions The long-term postenucleation implant exposure was rare after PP implant insertion and ACPT, even with a 20 mm-diameter implant. A larger implant can be beneficial in long-term prevention of eyelid malposition. [ABSTRACT FROM AUTHOR]