Long-term Outcomes of Surgeries for Retinal Detachment Secondary to Parasitic or Viral Infectious Retinitis.

PURPOSE: This study sought to compare the long-term outcomes of surgeries for retinal detachment (RD) secondary to viral or parasitic infectious retinitis. METHODS: A total of 47 eyes that received pars plana vitrectomy with or without scleral buckling due to RD secondary to polymerase chain reaction-proven viral (cytomegalovirus, varicella zoster virus, and herpes zoster virus) or parasitic (toxoplasma and toxocara) retinitis from October 1, 2006, to June 30, 2023, in a single medical center were retrospectively enrolled. RESULTS: Mean follow-up period was 59.03 ± 55.24 months in viral retinitis and 34.80 ± 33.78 months in parasitic retinitis after primary reattachment surgery. During follow-up, nine eyes (24.3%) with viral retinitis and five eyes (50.0%) with parasitic retinitis developed retinal redetachment. Visual acuity success at final follow-up was achieved in 19 eyes (51.4%) with viral retinitis and six eyes (60.0%) with parasitic retinitis (p = 0.64). The incidence of retinal redetachment during the 1st postoperative year was significantly higher in parasitic retinitis compared with viral retinitis (crude incidence, 0.21 vs. 0.85; p = 0.02). Hazard ratio analysis adjusted for age and sex showed 4.58-fold (95% confidence interval, 1.22-17.27; p = 0.03) increased risk of retinal redetachment in parasitic retinitis compared with viral retinitis during the 1st postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis. CONCLUSIONS: Compared with RD secondary to viral retinitis, RD secondary to parasitic retinitis showed higher incidence of retinal redetachment during the 1st postoperative year. Tamponade with silicone oil and preoperative diagnostic vitrectomy were associated with significantly decreased risk of retinal redetachment in patients with parasitic retinitis.

Factors predicting redislocation or suture-break in eyes after scleral-fixated intraocular lens.

PURPOSE: To investigate predictive factors for redislocation in patients with recurrent intraocular lens (IOL) dislocation following secondary scleral-fixated IOL (SFIOL) surgery. SETTING: Two tertiary referral hospitals. DESIGN: Retrospective case series. METHODS: Patients undergoing SFIOL surgery were grouped into redislocation and no-redislocation groups. Medical records of consecutive patients who underwent SFIOL surgery between June 2014 and December 2019 at two tertiary referral centers were reviewed. Data regarding patient demographics, treatment factors, anatomical and functional outcomes, and postoperative complications were recorded. RESULTS: We included 237 eyes of 225 patients (169 [75.1%] men). The redislocation group was more likely to have a younger mean age at the initial SFIOL surgery (redislocation vs no-redislocation, 55.4 vs 62.0 years, respectively; P=0.008), have a prior history of a previous suture-break (23 eyes, 52.3% vs 1 eye, 0.5%; P<0.001), and have undergone the initial SFIOL surgery using <1 mm-sized side-port incisions (17 eyes, 38.6% vs 32 eyes, 16.5%; P=0.002) than was the no-redislocation group. Additionally, the redislocation group had a higher occurrence of complications (P<0.001). Multivariable regression revealed that younger age, left eye involvement, aphakic status prior to the surgery, unremarkable primary IOL dislocation cause, need for ocular hypertension treatment and glaucoma surgery, and no large incision during the initial surgery were significantly (all P<0.05) associated with redislocation. CONCLUSION: Younger age, left eye involvement, postoperative complications like ocular hypertension and glaucoma, and techniques without large incisions increase the risk of redislocation. Conversely, lower risk factors include unremarkable surgery causes and a history of aphakic conditions.

Pose Tracking of Supermicrosurgical Robot Towards Multi-User Teleoperation.

This paper presents pose tracking experiments using a supermicrosurgical robot designed to consider teleoperation with multiple surgeons. Currently, existing supermicrosurgical robots assist only the primary surgeon. However, both primary and assistant surgeons need a high-precision motion for critical tasks that can easily damage microtissue. To assist multiple surgeons in supermicrosurgery with a surgical robot, dynamic collision avoidance becomes a critical issue due to the operation in a narrow surgical site. As a milestone to overcome this issue, we first developed a pose tracking algorithm by analyzing the inverse kinematics based on null-space control and a weighting matrix. Moreover, we also developed a control framework based on fully open-source software to run the pose tracking algorithm. Finally, we validated the proposed pose tracking algorithm by performing line tracing and rubber ring transferring experiments.

Next-Generation Sequencing of Vitreoretinal Lymphoma by Vitreous Liquid Biopsy: Diagnostic Potential and Genotype/Phenotype Correlation.

Purpose: To determine the diagnostic potential of next-generation sequencing (NGS) in vitreous samples, analyze genotype-phenotype characteristics, and compare NGS of matched vitreous and brain samples in patients with associated central nervous system lymphoma (CNSL). Methods: A total of 32 patients suspected of vitreoretinal lymphoma (VRL) who underwent diagnostic vitrectomy and NGS were included in this retrospective observational case-series. Fresh vitreous specimens from diagnostic vitrectomy of VRL-suspected patients underwent NGS using a custom panel targeting 747 candidate genes for lymphoma. They also underwent malignancy cytology, interleukin (IL)-10/IL-6, immunoglobulin heavy chain (IGH)/immunoglobulin kappa light chain (IGK) monoclonality testing. MYD88 L265P mutation was examined from anterior chamber tap samples. The diagnosis of VRL was made based on typical clinical characteristics for VRL, as well as malignant cytology, IGH/IGK clonality, or IL-10/IL-6 > 1. Sensitivity and specificity of NGS were compared with conventional diagnostic tests. Brain tissues suspected of lymphoma were collected by stereotactic biopsy and underwent NGS. Genetic variations detected in NGS of vitreous and brain tissue specimens were compared. Results: The sensitivity values for cytology, IL-10/IL-6 > 1, clonality assays for IGH and IGK, MYD88 L265P detection in anterior chamber tap samples, and vitreous NGS were 0.23, 0.83, 0.68, 0.79, 0.67, and 0.85, with specificity values of 1.00, 0.83, 0.50, 0.25, 0.83, and 0.83, respectively. The sensitivity (0.85) of vitreous NGS was the highest compared to other conventional diagnostic tests for VRL. The most common mutations were MYD88 (91%), CDKN2A (36%), PIM1 (32%), IGLL5 (27%), and ETV6 (23%). Although several gene alterations demonstrated heterogeneity between the brain and eyes, some common mutational profiles were observed in matched vitreous and brain samples. Conclusions: Overall, NGS of the vitreous demonstrated high sensitivity among conventional diagnostic tests. VRL and CNSL appeared to have both shared and distinct genetic variations, which may suggest site-specific variations from a common origin.

ßTrCP1 promotes SLC35F2 protein ubiquitination and inhibits cancer progression in HeLa cells.

The solute carrier family 35 F2 (SLC35F2) belongs to membrane-bound carrier proteins that are associated with multiple cancers. The main factor that determines cancer progression is the expression level of SLC35F2. Thus, identifying the E3 ligase that controls SLC35F2 protein abundance in cancer cells is critical. Here, we identified ßTrCP1 interacting with and reducing the SLC35F2 protein level. ßTrCP1 signals SLC35F2 protein ubiquitination and reduces SLC35F2 protein half-life. The mRNA expression pattern between ßTrCP1 and SLC35F2 across a panel of cancer cell lines showed a negative correlation. Additionally, the depletion of ßTrCP1 accumulated SLC35F2 protein and promoted SLC35F2-mediated cell growth, migration, invasion, and colony formation ability in HeLa cells. Overall, we demonstrate that ßTrCP1 acts as a tumor suppressor by controlling SLC35F2 protein abundance in cancer cells. The depletion of ßTrCP1 promotes SLC35F2-mediated carcinogenesis. Thus, we envision that ßTrCP1 may be a potential target for cancer therapeutics.

Impact of guideline-directed medical therapy on 5-year mortality in patients with newly diagnosed peripheral artery disease.

OBJECTIVE: Current guidelines recommend that patients with peripheral artery disease (PAD) should be treated with antithrombotic agents, renin-angiotensin-system blockers, and statins. However, the clinical impact of guideline-directed medical therapy (GDMT) on long-term mortality in patients with newly diagnosed PAD remains unclear. We aimed to investigate the prevalence of GDMT and evaluate 5-year mortality according to GDMT after PAD diagnosis. METHODS: This retrospective cohort study, using nationwide health insurance claims data in Korea, included patients newly diagnosed with PAD between 2006 and 2015. GDMT was defined as the use of all drugs, including antithrombotic agents, renin-angiotensin-system blockers, and statins, within 3 months of PAD diagnosis. The primary endpoint was all-cause mortality. RESULTS: We investigated 19,561 newly diagnosed patients with PAD without proven cardiovascular disease. Among the study population, 4378 patients (22.4%) were categorized in the GDMT and 15,183 (77.6%) in the non-GDMT groups. During the 5-year follow-up, GDMT showed a lower incidence of all-cause mortality than that of non-GDMT (2.8% vs 4.8%; adjusted hazard ratio, 0.329; 95% confidence interval, 0.257-0.421; P < .001). Even in the propensity-matched population, GDMT showed a lower mortality rate than non-GDMT (hazard ratio, 0.283; 95% confidence interval, 0.217-0.370; P < .001). As the number of guideline-recommended drugs increased, the mortality rate decreased proportionately. CONCLUSIONS: After PAD diagnosis, GDMT was associated with a lower incidence of mortality regardless of proven cardiovascular disease. This retrospective analysis showed an insufficient prevalence of GDMT among patients with PAD in real-world practice.

Ginsenoside Rg2 inhibits osteoclastogenesis by downregulating the NFATc1, c-Fos, and MAPK pathways.

Ginsenosides, among the most active components of ginseng, exhibit several therapeutic effects against cancer, diabetes, and other metabolic diseases. However, the molecular mechanism underlying the anti-osteoporotic activity of ginsenoside Rg2, a major ginsenoside, has not been clearly elucidated. This study aimed to determine the effects of ginsenoside Rg2 on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. Results indicate that ginsenoside Rg2 inhibits RANKLinduced osteoclast differentiation of bone marrow macrophages (BMMs) without cytotoxicity. Pretreatment with ginsenoside Rg2 significantly reduced the RANKL-induced gene expression of c-fos and nuclear factor of activated T-cells (Nfatc1), as well as osteoclast-specific markers tartrate-resistant acid phosphatase (TRAP, Acp5) and osteoclast-associated receptor (Oscar). Moreover, RANKL-induced phosphorylation of mitogen-activated protein kinases (MAPKs) was decreased by ginsenoside Rg2 in BMM. Therefore, we suggest that ginsenoside Rg2 suppresses RANKLinduced osteoclast differentiation through the regulation of MAPK signaling-mediated osteoclast markers and could be developed as a therapeutic drug for the prevention and treatment of osteoporosis. [BMB Reports 2023; 56(10): 551-556].

One-stage reconstruction using a fibula osteocutaneous free flap and an anterolateral thigh free flap for an extensive composite defect after en bloc resection of squamous cell carcinoma on the mouth floor, mandible, and anterior neck: A CARE-compliant case report.

RATIONALE: Although regional metastasis to the lymph nodes is common in advanced oral cancer, extensive local invasion into surrounding structures such as the mandible, skin and soft tissue of the neck, and masticator space is relatively rare. Sometimes surgical treatment cannot be performed and only palliative chemotherapy and radiation therapy are offered to preserve the quality of life of patients with advanced oral cancer. Nevertheless, the surgical resection of tumors remains the most effective treatment. This study presents a case of aggressive mouth floor cancer in which extensive composite defects on the mouth floor, oral mucosa, mandible, skin and soft tissue of the neck caused by tumor resection were reconstructed. PATIENT CONCERNS: A 66-year-old man and a 65-year-old man with no significant personal or family history visited our clinic due to a large and multiple masses on the floor of the mouth and both sides of the neck. DIAGNOSIS: Histopathological evaluation of the biopsy specimen revealed squamous cell carcinoma. INTERVENTIONS: A fibula osteocutaneous free flap and customized titanium plate were used for the intraoral lining. Mandibular reconstruction was performed using a 3D-printed bone model, and an anterolateral thigh free flap was used to resurface the anterior of the neck. OUTCOMES: Reconstruction using this method was successful, and excellent functional and aesthetic outcomes were achieved without cancer recurrence. LESSONS: This study show that the reconstruction of extensive composite defects of the oral mucosa, mandible, and neck soft tissue following surgical resection of mouth floor cancer can be performed in a single-stage operation. Through a single-stage reconstruction, both excellent functional aspects without cancer recurrence and satisfactory aesthetic outcomes can be obtained.

Clinical Features, Long-Term Outcomes, and Prognostic Factors of Eales' Disease in Korean Patients.

PURPOSE: We studied Korean patients with Eales' disease to document clinical features, long-term outcomes, and explore its association with TB, given South Korea's high TB burden. METHODS: We retrospectively reviewed medical records of Eales' disease patients for clinical characteristics, long-term outcomes, and its association with TB. RESULTS: Among 106 eyes, the average age of diagnosis was 39.28 years, with 82.7% male and 58.7% having unilateral involvement. Patients who underwent vitrectomy showed greater long-term improvement in visual acuity (P = .047), while those with glaucoma filtration surgery showed less improvement (P = .008). Having glaucoma through disease progression was associated with poor visual outcomes (odds ratio=15.556, P < .02). 27 out of 39 patients (69.23%) who underwent IGRA screening tested positive for TB. CONCLUSIONS: In Korean patients with Eales' disease, we observed male predominance, unilateral presentation, older age of onset, and a link with TB. Timely diagnosis and management should be considered to maintain good vision in patients with Eales' disease.

CRISPR/Cas9 mediated specific ablation of vegfa in retinal pigment epithelium efficiently regresses choroidal neovascularization.

The CRISPR/Cas9 system easily edits target genes in various organisms and is used to treat human diseases. In most therapeutic CRISPR studies, ubiquitously expressed promoters, such as CMV, CAG, and EF1α, are used; however, gene editing is sometimes necessary only in specific cell types relevant to the disease. Therefore, we aimed to develop a retinal pigment epithelium (RPE)-specific CRISPR/Cas9 system. We developed a CRISPR/Cas9 system that operates only in retinal pigment epithelium (RPE) by expressing Cas9 under the RPE-specific vitelliform macular dystrophy 2 promoter (pVMD2). This RPE-specific CRISPR/pVMD2-Cas9 system was tested in human retinal organoid and mouse model. We confirmed that this system works specifically in the RPE of human retinal organoids and mouse retina. In addition, the RPE-specific Vegfa ablation using the novel CRISPR-pVMD2-Cas9 system caused regression of choroidal neovascularization (CNV) without unwanted knock-out in the neural retina in laser-induced CNV mice, which is a widely used animal model of neovascular age-related macular degeneration. RPE-specific Vegfa knock-out (KO) and ubiquitous Vegfa KO were comparable in the efficient regression of CNV. The promoter substituted, cell type-specific CRISPR/Cas9 systems can be used in specific 'target cell' therapy, which edits genes while reducing unwanted off- 'target cell' effects.

Therapeutic effect of modified double-dose photodynamic therapy in circumscribed choroidal haemangioma.

AIMS: To retrospectively compare the therapeutic effect of modified double-dose photodynamic therapy (PDT) with standard-dose PDT in patients with circumscribed choroidal haemangioma (CCH). METHODS: Thirty-nine patients with CCH were categorised in two groups by PDT type. The standard-dose group (n=12) was treated with 6 mg/m2 verteporfin and a 689 nm laser for 83 s. The modified double-dose group (n=27) received one vial of verteporfin (15 mg), and the dose was calculated for each patient based on body surface area, then irradiance time was adjusted according to calculated verteporfin dose to achieve a 'double'-dose effect. Treatment outcomes (foveal centre thickness, subretinal fluid, tumour thickness and diameter) were measured at baseline and 1 year post-treatment; subretinal fluid levels were also measured at 1, 3 and 6 months post-treatment. RESULTS: No differences in baseline characteristics were found between the two groups. The modified double-dose group showed a greater reduction in tumour thickness (45.3% vs 20.6%, p=0.013) and tumour volume (60.0% vs 30.0%, p=0.006) at 1 year post-treatment. Recurred or non-complete resolution patients in the standard-dose group tended to show much increased subretinal fluid than those in the modified double-dose group at 1-year post-treatment. CONCLUSION: Modified double-dose PDT is an effective and safe protocol for symptomatic CCH management, greater tumour regression and potentially better resolution of subretinal fluid compared with standard PDT.

Clinical and Multimodal Imaging Features of Choroidal Nevi in the Korean Population.

Choroidal nevus is a precursor of choroidal melanoma. Multimodal imaging has become vital in predicting the malignant transformation of choroidal nevi. This single-center, retrospective study analyzed clinical characteristics and multimodal imaging findings of 168 choroidal nevi (164 patients) of the Korean population. The mean age at presentation was 50 ± 15 (range, 13−85) (women, n = 88 [53.7%]). Choroidal nevi (melanotic, n = 164 [97.6%]; postequatorial, n = 160 [95.2%]) were densely located between the optic disc and foveola (65.5%). The mean maximum linear basal diameter on fundus photography and thickness on optical coherence tomography were 2.97 ± 1.51 mm and 521 ± 297 µm, respectively. On ultrasonography, the mean thickness was 0.87 ± 0.60 mm. Choroidal nevi in women were associated with a higher maximum linear basal diameter (3.23 ± 1.65 vs. 2.68 ± 1.21 mm; p = 0.033) and age at diagnosis (52 ± 14 vs. 47 ± 16 years; p = 0.046) than those in men. Choroidal nevi with associated subretinal fluid (23.2%) presented with larger basal diameter (p = 0.049) and thickness on B-scan and optical coherence tomography (p < 0.001), but a younger age at diagnosis (p < 0.001) than those of dry nevi. This multimodal imaging study of choroidal nevi revealed some distinct characteristics, including topographic distribution, sex-related differences, and a younger age at diagnosis of nevi with fluid.

Diagnostic Accuracy of Vitreous Cytology in Patients with Vitreoretinal Lymphoma.

(1) Background: To determine the diagnostic value of vitreous cytology in patients with vitreoretinal lymphoma (VRL) and evaluate its diagnostic accuracy relative to that of other diagnostic tests. (2) Methods: In total, 38 eyes from 38 patients with VRL who underwent diagnostic vitrectomy and were followed up for at least 6 months were analyzed. The clinical manifestations and VRL diagnostic rates for all diagnostic tests were determined. (3) Results: The presence of vitreous cells/opacity was the most common ophthalmic finding (97.4%), followed by sub-retinal pigment epithelial infiltration (65.8%) and retinal hemorrhage (21.1%). The VRL diagnostic rates were 89.3% for interleukin (IL)-10 levels > 50 pg/mL; 82.1% for IL-10/IL-6 ratios > 1; 60.0% and 63.3% for immunoglobulin heavy chain and kappa light chain clonality assays, respectively; and 44.4% for vitreous cytology. The VRL diagnostic rate for vitreous cytology was significantly lower in the steroid pretreatment group than in the non-steroid pretreatment group (p = 0.007). (4) Conclusions: The VRL detection rate for vitreous cytology was lower than that for the other tests, especially in patients who received steroid pretreatment. These findings suggest that even if vitreous cytology findings are negative, other tests and characteristic fundus findings should be evaluated to confirm VRL diagnosis.

Predicting Visual Outcomes in Choroidal Osteoma Treated with Anti-vascular Endothelial Growth Factor.

PURPOSE: To determine potential factors associated with the long-term visual prognoses in patients with choroidal osteoma undergoing anti-vascular endothelial growth factor (VEGF) treatment. DESIGN: Retrospective case series. METHODS: Patients diagnosed at tertiary high-volume hospitals between January 2000 and December 2020 were evaluated. The primary outcome measure was visual acuity at 5-year follow-up. The secondary outcome measures included factors associated with favorable vision, defined as loss of <1 line and >20/200 vision. RESULTS: Of 38 eyes from 36 patients (22 female, 61%; mean age 38 years) with choroidal osteoma, 23 eyes (61%) received anti-VEGF treatment (bevacizumab 1.25mg/0.05 cc, monthly or treat-and-extend) and 65% completed the 5 years of follow-up. All treated eyes had associated chorioretinal comorbidities (subretinal fluid 91%; choroidal neovascularization 74%; subretinal hemorrhage 30%). Although there was significant vision loss by 5 years (P = .002), 12 eyes (44%) had favorable outcomes. Only tumor thickness was significantly associated with unfavorable visual outcomes (OR 917.1, 95% CI 1.0-5687.7; P = .049). The optimal cut-off point predictive of visual outcomes was 1.4 mm, and tumor thickness ≥ 1.4 mm was associated with unfavorable vision (OR 27.0, 95% CI 2.0-368.4; P = .013). CONCLUSIONS: Among patients with choroidal osteoma undergoing anti-VEGF therapy, a particular patient subset presented with divergent outcomes with very poor vision. Tumor thickness appeared to be the differentiating factor and is thus a potential prognostic indicator for long-term visual prognoses.

Inhibitory Effect of Biotransformed-Fucoidan on the Differentiation of Osteoclasts Induced by Receptor for Activation of Nuclear Factor-κB Ligand.

Bone homeostasis is regulated by constant remodeling through osteogenesis by osteoblasts and osteolysis by osteoclasts and osteoporosis can be provoked when this balance is broken. Present pharmaceutical treatments for osteoporosis have harmful side effects and thus, our goal was to develop therapeutics from intrisincally safe natural products. Fucoidan is a polysaccharide extracted from many species of brown seaweed, with valuable pharmaceutical activities. To intensify the effect of fucoidan on bone homeostasis, we hydrolyzed fucoidan using AMG, Pectinex and Viscozyme. Of these, fucoidan biotransformed by Pectinex (Fu/Pec) powerfully inhibited the induction of tartrate-resistant acid phosphatase (TRAP) activity in osteoclasts differentiated from bone marrow macrophages (BMMs) by the receptor for activation of nuclear factor-κB ligand (RANKL). To investigate potential of lower molecular weight fucoidan it was separated into >300 kDa, 50-300 kDa, and <50 kDa Fu/Pec fractions by ultrafiltration system. The effects of these fractions on TRAP and alkaline phosphatase (ALP) activities were then examined in differentiated osteoclasts and MC3T3-E1 osteoblasts, respectively. Interestingly, 50-300 kDa Fu/Pec suppressed RANKL-induced osteoclasts differentiation from BMMs but did not synergistically enhance osteoblasts differentiation induced by osteogenic agents. In addition, this fraction inhibited the expressions of NFATc1, TRAP, OSCAR, and RANK, which are all key transcriptional factors involved in osteoclast differentiation, and those of Src, c-Fos and Mitf, as determined by RT-PCR. In conclusion, enzymatically low-molecularized 50-300 kDa Fu/Pec suppressed TRAP by downregulating RANKL-related signaling, contributing to the inhibition of osteoclasts differentiation, and represented a potential means of inducing bone remodeling in the background of osteoporosis.

Complications, treatments, and visual prognosis of choroidal osteomas.

PURPOSE: This study aims to report complications, treatments, and visual prognosis of choroidal osteoma. METHODS: We retrospectively reviewed electronic medical records and multimodal images of 41 patients with choroidal osteoma. RESULTS: Visually significant complications included choroidal neovascularization (CNV) in 21 (47.7%) eyes and subretinal fluid (SRF) without CNV in 14 (31.8%) eyes. The most common treatment was intravitreal anti-vascular endothelial growth factor (VEGF) injection: 13 (61.9%) eyes with CNV received an average of 6.3 injections, and 6 (42.9%) eyes with SRF but without CNV received 1.8 injections. As the first-line treatment, intravitreal anti-VEGF injection induced complete or partial remission in 93.4% of eyes with CNV and 57.1% of eyes with SRF. The probability of legally low vision estimated at 3 and at 5 years was 29.1% and 34.2%, respectively. The presence of CNV and outer retinal tubulation (ORT) was independent risk factors for vision loss (adjusted odds ratio, 8.08 and 6.94, respectively). CONCLUSIONS: The development of CNV and ORT was strong risk factors for visual impairment. Due to the frequent recurrence of complications and poor visual prognosis, regular check-ups and appropriate treatment choices are warranted.

Clinical features and long-term treatment outcomes in choroidal tuberculoma.

PURPOSE: To investigate the clinical features and treatment outcomes of patients with choroidal tuberculoma. METHODS: In this retrospective, observational case series, the medical records of five patients with choroidal tuberculoma who were followed up at a university hospital for at least 6 months were analyzed. RESULTS: Of five patients, one was male and four were female. The overall mean age was 38.0 ± 9.4 years (mean follow-up: 41.2 ± 33.8 months). Tuberculin skin test was performed in three patients, and it was positive in two of them. Interferon-gamma assay was performed in two patients and was positive in all two. Three patients had systemic tuberculosis involving the lung or other organs. Five patients were treated with antitubercular therapy for a period of 9.6 ± 8.6 months. Systemic corticosteroid treatment was performed in 3 patients, with a period of 3.5 ± 0.7 months. One patient with a recurrent vascularized tuberculoma was successfully treated with single intravitreal bevacizumab injection. CONCLUSION: Choroidal tuberculoma can develop without evidence of systemic tuberculosis and can recur despite antitubercular treatment. High index of suspicion is important in early detection, and management of choroidal tuberculoma. In cases of suspected choroidal tuberculoma, positive results on immunological tests would be sufficient to initiate antitubercular therapy even if radiological evidence of systemic tuberculosis is not found. Antitubercular therapy combined with systemic corticosteroids provided favorable results. Intravitreal injection of anti-vascular endothelial growth factor may be considered for highly vascularized choroidal tuberculoma.

Paired comparisons of mutational profiles before and after brachytherapy in asian uveal melanoma patients.

Uveal melanoma(UM) is the most common primary intraocular malignancy in adults. However, the incidence of UM in Asia is 10 to 20 times less than in Western populations. Therefore, for the first time, we report our whole exome sequencing (WES) data analysis to discover differences in the molecular features of Asian and Western UM, and to determine the disparities between the primary tumor before brachytherapy and enucleated samples after brachytherapy. WES of 19 samples (13 primary tumors, 5 enucleation samples after brachytherapy, and 1 liver metastasis) from 13 patients diagnosed with UM and treated between 2007 and 2019 at the Yonsei University Health System (YUHS) were analyzed using bioinformatics pipelines. We identified significantly altered genes in Asian UM and changes in mutational profiles before and after brachytherapy using various algorithms. GNAQ, BAP1, GNA11, SF3B1 and CYSLTR2 were significantly mutated in Asian UM, which is similar that reported frequently in previous Western-based UM studies. There were also similar copy number alterations (M3, 1p loss, 6p gain, 8q gain) in both groups. In paired comparisons of the same patients, DICER1 and LRP1B were distinctly mutated only in tumor samples obtained after brachytherapy using rare-variant association tests (P = 0.01, 0.01, respectively). The mutational profiles of Asian UM were generally similar to the data from previous Western-based studies. DICER1 and LRP1B were newly mutated genes with statistical significance in the regrowth samples after brachytherapy compared to the primary tumors, which may be related to resistance to brachytherapy.

Serial Detection of MYD88 L265P Mutation in the Aqueous Humor of a Patient with Vitreoretinal Lymphoma for Disease Monitoring.

PURPOSE: To report a case of a patient whose MYD88 mutation disappeared from the aqueous humor following treatment with intravitreal methotrexate. METHODS: A retrospective review of clinical, histopathological and imaging records. RESULTS: A 49-year-old woman presented with bilateral primary vitreoretinal lymphoma confirmed by molecular and next-generation sequencing studies on vitreous biopsy samples. Initially, the MYD88 L265P mutation was detected in aqueous samples of both eyes. Serial testing for MYD88 L265P mutations performed on aqueous samples collected at the time of the weekly intravitreal methotrexate injections showed the mutation ceased to be detected after four weekly injections in the non-vitrectomized right eye and after two weekly injections in the vitrectomized left eye. Clinical improvement accompanied the negativization of the mutation in both eyes. CONCLUSION: We present a case that demonstrates the possible utilization of serial testing for the MYD88 L265P mutation as a tool for monitoring disease course in vitreoretinal lymphoma.