OCTA biomarkers in adults aged 50 and above: a prospective and cross-sectional community-based study.

BACKGROUND/AIMS: To assess the normative values and parameters of optical coherence tomography angiography (OCTA) influencing the best corrected visual acuity (BCVA) in adults aged 50 and above. METHODS: This was a prospective cross-sectional study from an eye screening programme in Hong Kong for 4188 citizens aged 50 and above. Images were analysed using a validated quantification software calculating vessel density and capillary perfusion density (CPD), along with other OCTA parameters, such as the foveal avascular zone area (FAZ) and circularity. OCTA data was collected from May 2019 to December 2020, including a total of 4188 healthy eyes from 4188 subjects. RESULTS: Mean superficial vessel density (MSVD) was 14.48 ± 3.60 mm- 1, while the mean capillary perfusion density (MCPD) was 0.41 ± 0.06. Multivariate analysis revealed ageing (ß = 0.321, p < 0.001), being male (ß=-0.089, p < 0.001), having a high body mass index (BMI) (ß = 0.039, p = 0.006), high FAZ area and low FAZ circularity (ß = 0.039 and - 0.034, p = 0.01 and 0.024 respectively), low MSVD in the outer ring (ß=-0.513, p < 0.001), specifically in the nasal and temporal outer quadrants (ß = -0.226 and - 0.259, p < 0.001 for both), and low MCPD in the outer superior quadrant (ß= -0.123, p = 0.016) being independently associated with BCVA. CONCLUSION: High FAZ area and low FAZ circularity, low MSVD in the outer ring, specifically the nasal and temporal outer quadrants, and low MCPD in the outer superior quadrant can be used as biomarkers in predicting a low visual acuity in adults aged 50 and above.

Exploring Patient Motivations and Impact of Asian Blepharoplasty.

To date, patient motivations for Asian blepharoplasty and the surgery's impact on quality of life have not been quantified. Here, we employed structured interviews and a web-based survey to better characterize patient motivations for Asian blepharoplasty and the impact of Asian blepharoplasty on self-reported domains of happiness, self-esteem, attractiveness, social life, and professional life. Structured interviews were conducted to inform a web-based survey regarding Asian blepharoplasty. Survey respondents used visual analog scales to rate their satisfaction with their eye shape, motivations for undergoing Asian blepharoplasty, and perceived outcomes after surgery. A total of 315 participants (mean 25.7 [18-58] years) of East or Southeast Asian descent were included. 185 participants expressed no desire for Asian blepharoplasty, 76 expressed some desire, and 54 had already undergone surgery. There were statistically significant differences regarding baseline satisfaction, perceived social limitation, and perceived professional limitations regarding eye shape (p < 0.0001). The Looking Glass Self index (comprised of media exposure, low self-esteem, and negative stereotypes related to eye shape) is negatively associated with preoperative satisfaction with eye shape (rho = -0.29, p < 0.01). The desire for social-professional advancement and the Looking Glass Self index significantly predict self-reported improvements in professional and social life, respectively (both p < 0.01). Asian blepharoplasty may be driven by functional, social, or economic patient motivations. Some patients may see Asian blepharoplasty as a potential solution for sociological concerns. These expectations should be further explored in physician-patient discussions regarding candidacy for surgery and establishing expectations for postoperative outcomes.

Premium intraocular lens implantation in eyes with vitrectomy done.

PURPOSE: Phacoemulsification with premium intraocular lens (IOL) implantation has been increasingly popular in the recent years. However, it is not commonly implanted in eyes who had underwent previous vitrectomy surgery as the contrast sensitivity is thought to be reduced and surgeons are worried about poor visualization of the posterior segment after implantation. Since cataract and vitreoretinal diseases often coexist, premium IOLs should be a considerable option for implantation in carefully selected cases. This study aims at reporting the postoperative near and distance visual acuity and subjective quality of vision in eyes with premium IOLs implantation and vitrectomy done. METHODS: Twenty eyes with posterior vitrectomy and premium IOL implantation from 2006 to 2018 were included. Fourteen eyes were included in Group 1 with patients who underwent a combined phacovitrectomy surgery in the same setting, and six eyes were included in Group 2 with patients who received premium IOL implantation after previous posterior vitrectomy. RESULTS: Both the postoperative corrected distance and near visual acuity at 1 month, 3 month and 1 year are improved in both groups. The subjective quality of vision as graded by the National Eye Institute Refractive Error Quality of Life Instrument-42 questionnaire also showed high patient satisfaction in both groups. CONCLUSION: We conclude that the presence of a multifocal IOL does not impede visualization of the posterior segment during vitrectomy surgery and surgical complications were not raised. With careful patient selection and preoperative assessment, premium IOLs can be a considerable option in patients requiring posterior vitrectomy. TRIAL REGISTRATION: Retrospectively registered with the HKSH Medical Group Research Committee (Ref No. RC-2019-31, Date of registration: December 13, 2019).

The prevalence of human papillomavirus in oropharyngeal cancer is increasing regardless of sex or race, and the influence of sex and race on survival is modified by human papillomavirus tumor status.

BACKGROUND: The purpose of this study was to evaluate the influence of sex and race/ethnicity upon prevalence trends of human papillomavirus (HPV) in oropharyngeal cancer (OPC) and survival after OPC. METHOD: This was a cohort study of patients included in the United States National Cancer Database who had been diagnosed with OPC between 2010 and 2015. Outcomes were HPV status of tumor specimens and overall survival. Sex- and race-stratified trends in HPV prevalence were estimated using generalized linear modeling. The influence of sex, race, and HPV tumor status on overall survival was compared by Kaplan-Meier method and Cox Proportional Hazards models. RESULTS: This analysis included 20,886 HPV-positive and 10,364 HPV-negative OPC patients. The prevalence of HPV-positive tumors was higher among men (70.6%) than women (56.3%) and increased significantly over time at a rate of 3.5% and 3.2% per year among men and women, respectively. The prevalence of HPV-positive tumors was highest among whites (70.2%), followed by Hispanics (61.3%), Asians (55.8%), and blacks (46.3%). Blacks and Hispanics experienced significantly more rapid increases in prevalence of HPV-positive tumors over time compared with whites (6.5% vs 5.6% vs 3.2% per year, respectively). In HPV-positive OPC, neither sex nor race/ethnicity was associated with survival among patients with HPV-positive OPC. In contrast, for HPV-negative OPC, risk of death was significantly higher for women versus men (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.08-1.26) and blacks versus whites (aHR, 1.21; 95% CI, 1.10-1.33). CONCLUSION: The prevalence of HPV-positive tumors is increasing for all sex and race/ethnicity groups in the United States. Sex and race are independently associated with survival for HPV-negative but not HPV-positive OPC.

Stretched Earlobe Piercings Negatively Impact Casual Observer Perceptions.

Patients with stretched earlobes seek reconstruction to mitigate social stigma. To date, there have been no studies measuring the impact of stretched earlobe piercings on casual observer perceptions. One-hundred seventy-three casual observers were enrolled via public-access web sites. Participants were randomly shown frontal and profile views of six subjects with stretched earlobe piercings and four controls. Participants evaluated photos for first impressions using a survey containing choices regarding personal attributes. Latent class analysis was performed to categorize observer ratings. Analysis of variance (ANOVA), bootstrap analysis, and permutations testing were used to evaluate the relationship between perceived attractiveness, success, and approachability scoring and stretched earlobe status. Latent class analysis categorized responses into three classes: positive, negative, and neutral. Patients with stretched earlobe piercings were significantly less likely to be classified as positive by observers without body modifications (i.e., tattoos and piercings) in comparison to control photos (30.9 and 40.1%, p = 0.007) and more likely to be classified as negative (38.5 and 28.1%, p = 0.002). These changes were abolished when photos were evaluated by observers with body modifications (p > 0.05). ANOVA revealed that stretched earlobe piercings and observer body modification status have a significant effect on rated approachability (F [1,1726] = 4.08, p = 0.04) and successfulness (F[1,1726] = 9.67, p = 0.002; F [1,1726] = 70.33, p < 0.0005). No significance was found for rated attractiveness (p > 0.05). Patients with stretched earlobe piercings were more likely to be classified as having negative affect display and being less approachable and successful compared with controls when evaluated by observers without body modifications. This effect was abolished when photos were evaluated by observers with body modifications. These findings validate patient motivations for seeking stretched earlobe repair.

The role of human papillomavirus on the prognosis and treatment of oropharyngeal carcinoma.

Human papillomavirus positive oropharyngeal cancer (HPV-positive OPC) is a distinct subtype of head and neck carcinoma (HNC) distinguished from HPV-negative HNC by its risk factor profile, clinical behavior, and molecular biology. Compared to HPV-negative HNC, HPV-positive OPC exhibits significantly better prognosis and an enhanced response to treatment. Recognition of the survival benefit of HPV-positive tumors has led to therapeutic de-intensification strategies aiming to mitigate treatment-related toxicities while maintaining high response rates. In this review, we summarize key aspects of oral HPV infection and the molecular mechanisms of HPV-related carcinogenesis. We review the clinical and molecular characteristics of HPV-positive OPC that contribute to its improved prognosis compared to HPV-negative HNC. We also discuss current and emerging treatment strategies, emphasizing potential mechanisms of treatment sensitivity and the role of therapeutic de-intensification in HPV-positive OPC. Lastly, we examine literature on the management and prognosis of recurrent/metastatic HPV-positive OPC with a focus on the role of salvage surgery in its management.

ONE-YEAR RESULTS OF HALF- VERSUS STANDARD-DOSE PHOTODYNAMIC THERAPY COMBINED WITH RANIBIZUMAB FOR POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To explore the efficacy of half-dose verteporfin photodynamic therapy (hd-PDT) and standard-dose photodynamic therapy (sd-PDT), when combined with ranibizumab in the treatment of polypoidal choroidal vasculopathy. METHODS: Subjects were allocated to either the hd-PDT arm or the sd-PDT arm. All subjects received an injection of ranibizumab and PDT treatment (dosage according to allocation) at baseline. Subjects were followed up monthly for 12 months, and re-treatment were given at each visit if criteria were met. RESULTS: There were 26 subjects in the hd-PDT arm and 32 in the sd-PDT arm. Overall mean age was 69.3 ± 9.4 years. Baseline demographics and ocular features did not differ significantly between the two arms. Improvement in vision and reduction in central retinal thickness were similar between the two arms. When presenting, visual acuity was better than 20/50 (logarithm of the minimum angle of resolution 0.4), or when there were three or less polyps angiogram, those treated with hd-PDT tended to perform better than those treated with sd-PDT. CONCLUSION: In general, hd-PDT was able to produce similar results as sd-PDT. Subgroup analysis revealed superior results with hd-PDT when baseline vision was 20/50 or better, or when there were three or less polyps on indocyanine green angiography.

Beyond glycolysis: GAPDHs are multi-functional enzymes involved in regulation of ROS, autophagy, and plant immune responses.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is an important enzyme in energy metabolism with diverse cellular regulatory roles in vertebrates, but few reports have investigated the importance of plant GAPDH isoforms outside of their role in glycolysis. While animals possess one GAPDH isoform, plants possess multiple isoforms. In this study, cell biological and genetic approaches were used to investigate the role of GAPDHs during plant immune responses. Individual Arabidopsis GAPDH knockouts (KO lines) exhibited enhanced disease resistance phenotypes upon inoculation with the bacterial plant pathogen Pseudomonas syringae pv. tomato. KO lines exhibited accelerated programmed cell death and increased electrolyte leakage in response to effector triggered immunity. Furthermore, KO lines displayed increased basal ROS accumulation as visualized using the fluorescent probe H2DCFDA. The gapa1-2 and gapc1 KOs exhibited constitutive autophagy phenotypes in the absence of nutrient starvation. Due to the high sequence conservation between vertebrate and plant cytosolic GAPDH, our experiments focused on cytosolic GAPC1 cellular dynamics using a complemented GAPC1-GFP line. Confocal imaging coupled with an endocytic membrane marker (FM4-64) and endosomal trafficking inhibitors (BFA, Wortmannin) demonstrated cytosolic GAPC1 is localized to the plasma membrane and the endomembrane system, in addition to the cytosol and nucleus. After perception of bacterial flagellin, GAPC1 dynamically responded with a significant increase in size of fluorescent puncta and enhanced nuclear accumulation. Taken together, these results indicate that plant GAPDHs can affect multiple aspects of plant immunity in diverse sub-cellular compartments.

Outcome of extremely low birth weight infants with a history of neonatal acute kidney injury.

OBJECTIVE: To study the outcome of extremely low birth weight (ELBW) infants with a history of acute kidney injury (AKI). METHOD: In a retrospective, case control study, medical records of all ELBW infants admitted to the neonatal intensive care unit (NICU) between Jan 2002 and Dec 2011 were reviewed. Medical records were reviewed for infants' demographics, blood pressure (BP) at NICU discharge and at ≥3 years, and estimated glomerular filtration rate (eGFR) at ≥2 years. RESULTS: During the study period, 222 patients met the inclusion criteria, of whom 10% (23 out of 222) had AKI stage 2 and 3, 39% (87 out of 222) had AKI stage 1, and the rest did not have AKI. At NICU discharge, there was a difference in diastolic BP (DBP) among infants who had AKI stages 2 and 3, those who had stage 1, and those who did not have AKI (53 ± 12 vs 46 ± 9 vs 46 ± 11 mmHg respectively; p = 0.007), and 11% (23 out of 209) had hypertension (HTN). Although there was a significant correlation between the rise in SCr and DBP at NICU discharge in infants with AKI (R = 0.304; p = 0.004), there was no difference in HTN between infants with and those without AKI. At ≥2 years of age, 4% (5 out of 120) across all groups had an eGFR < 90 ml/min/1.73m2 or chronic kidney disease (CKD). At ≥3 years of age, 5% (11 out of 222) had HTN. CONCLUSION: At NICU discharge, infants with AKI stages 2 and 3 have a higher DBP than infants with stage 1 AKI and those who did not have AKI. However, there is no difference in the rate of HTN between the two groups. At ≥2 years ELBW infants are at risk for CKD independently of whether or not they develop neonatal AKI.

Subcategorization of Perineural Invasion Stratifies Oral Cavity Squamous Cell Carcinoma Prognosis.

OBJECTIVE: To evaluate whether subcategorization of perineural invasion (PNI) improves the prognostic resolution of the American Joint Committee on Cancer, Eighth Edition (AJCC8) staging system in oral cavity squamous cell carcinoma (OCSCC). METHODS: OCSCC tumor specimens from patients seen at a tertiary care institution who underwent primary surgical resection between January 2019 and June 2021 were sorted into four PNI categories: negative, intratumoral, peripheral, and extratumoral. The prognostic effect of these PNI categories were assessed through Kaplan-Meier, Cox regression, and log-rank testing using recurrence-free survival (RFS) and overall survival (OS) as primary and secondary outcomes respectively. RESULTS: A total of 158 patients were examined. The median follow-up time was 21 months. PNI subcategorization further stratified RFS (p = 0.007) and OS (p = 0.002). Extratumoral PNI was associated with a 4.5-fold increase in recurrence risk (adjusted hazards ratio [aHR]: 4.53; 95% confidence interval [CI]: 1.1-18.66) and worse OS when compared with PNI negative disease (aHR: 5.71; 95% CI: 1.0-32.67). Peripheral PNI was associated with worse OS (aHR: 5.7; 95% CI: 1.35-24.08) but not worse RFS (p = 0.18) when compared with PNI negative disease. Interestingly, intratumoral PNI was not associated with significant differences in RFS (p = 0.087) or OS (p = 0.22) when compared with PNI negative disease. CONCLUSIONS: Subcategorization of OCSCC tumors into extratumoral, peripheral, and intratumoral PNI stratifies RFS and OS when compared with patients with PNI negative disease in an incremental fashion. This pilot study suggests that there may be added benefit in subcategorization of PNI in the prognostic evaluation of OCSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1656-1662, 2024.

Nutraceuticals for Diabetic Retinopathy: Recent Advances and Novel Delivery Systems.

Diabetic retinopathy (DR) is a major vision-threatening disease among the working-age population worldwide. Present therapeutic strategies such as intravitreal injection of anti-VEGF and laser photocoagulation mainly target proliferative DR. However, there is a need for early effective management in patients with early stage of DR before its progression into the more severe sight-threatening proliferative stage. Nutraceuticals, natural functional foods with few side effects, have been proposed to be beneficial in patients with DR. Over the decades, many studies, either in vitro or in vivo, have demonstrated the advantages of a number of nutraceuticals in DR with their antioxidative, anti-inflammatory, neuroprotective, or vasoprotective effects. However, only a few clinical trials have been conducted, and their outcomes varied. The low bioavailability and instability of many nutraceuticals have indeed hindered their utilization in clinical use. In this context, nanoparticle carriers have been developed to deliver nutraceuticals and to improve their bioavailability. Despite its preclinical nature, research of interventive nutraceuticals for DR may yield promising information in their clinical applications.

Recurrence morbidity of olfactory neuroblastoma.

BACKGROUND: With modern treatment paradigms, olfactory neuroblastoma (ONB) has favorable overall survival (OS); however, the incidence of recurrence remains high. The primary aims of this study were to delineate the prognosis of recurrence of ONB and explore how recurrence subsites are associated with OS, disease-specific survival (DSS), and further recurrence. METHODS: A retrospective chart review of ONB cases from nine academic centers between 2005 and 2021 was completed. Tumor characteristics, recurrence subsites, timelines to recurrence, additional recurrences, and survival estimates were determined using descriptive and time-to-event analyses. RESULTS: A final cohort of 233 patients was identified, with 70 (30.0%) patients recurring within 50.4 (standard deviation ±40.9) months of diagnosis on average, consisting of local (50%), neck (36%), intracranial (9%), and distant (6%) recurrence. Compared with subjects without recurrence, patients with recurrence had significantly different primary American Joint Committee on Cancer T stage (p < 0.001), overall stage (p < 0.001), and modified Kadish scores (p < 0.001). Histopathology identified that dural involvement and positive margins were significantly greater in recurrent cases. First recurrence was significantly associated with worse 5-year DSS (hazard ratio = 5.62; p = 0.003), and subjects with neck or local recurrence had a significantly better DSS compared to intracranial or distant recurrence. CONCLUSIONS: Recurrent cases of ONB have significantly different stages and preoperative imaging factors. Patients with local or neck recurrence, however, have better DSS than those with intracranial or distant recurrence, independent of initial tumor stage or Hyams grade. Identifying specific factors that confer an increased risk of recurrence and DSS is important for patient counseling in addition to surveillance planning.

Ocular manifestations and diagnosis of tuberculosis involving the uvea: a case series.

BACKGROUND: Ocular tuberculosis (TB) affects 1-2% of patients with TB, with TB uveitis being the most common. This series aims to look at different manifestations of tuberculosis associated uveitis and the different tests used to make a presumptive or definitive diagnosis. METHODS: Patients diagnosed with TB related uveitis in Hong Kong SAR between 2017 and 2020 were reviewed. Demographics, clinical features, investigations and treatments of patients were collected. RESULTS: Fifteen eyes in 10 patients with a mean age 57.30 ± 10.17 years were included. The ocular manifestations on presentation included anterior uveitis (50%), posterior uveitis (40%) and panuveitis (10%), where 70% of them were unilateral and 30% were bilaterally infected; on subsequent visits the manifestations further developed into posterior uveitis (40%), panuveitis (40%) and anterior uveitis (20%), where 50% of them were unilateral and 50% bilateral infected. Tuberculosis tests were positive in 5 out of 7 Mantoux tests, 4 out of 4 T-SPOT TB tests, 3 out of 4 QuantiFERON-TB gold tests, 1 out of 1 lymph node biopsy, 0 out of 9 chest x-rays, and no aqueous fluid polymerase chain reaction (PCR) was tested. Vision impairing complications were seen in 6 patients where retinal vasculitis was most commonly seen. With anti-TB treatment prescribed in 9 patients, side effects occurred in 5 patients, including ocular hypertension, disc swelling, and hepatitis. CONCLUSIONS: Ocular TB infections may manifest in various forms, and can involve different parts of the eye. Bilateral involvement of TB is commonly presented, and both eyes should be evaluated at every follow up. When TB is suspected in a patient, diagnostic confirmation requires multimodal investigations where a negative chest x-ray is not useful in ruling out ocular TB infections, especially in an endemic region like Hong Kong. In these patients, it is crucial to have a high index of suspicion for TB, even when they do not demonstrate classical respiratory signs and symptoms of TB.

Performance, safety and efficiency comparison between 10,000 and 5000 cuts per minute vitrectomy using a 25G cutter: a prospective randomized controlled study.

PURPOSE: This study aims to compare the performance of the 25+® UltraVit® 5000 cuts per minute (cpm) vitrectomy probe versus the 25+ ® Ultravit 10,000 cpm® beveled tip, dual drive vitrectomy probe. METHOD: In this prospective randomised controlled clinical trial, 52 eyes of 52 consecutive patients were randomized into either the 10,000 cpm (25 patients) or 5000 cpm vitrectomy group (27 patients). Patients were evaluated preoperatively, intraoperatively, and postoperatively on the first day, and at 1 week, 1 month and 3 months. The main outcome measures were vitrectomy time, and secondary endpoints were time to induction of posterior vitreous detachment, intraoperative complications, and number of instruments used. RESULTS: The vitrectomy time was shorter in the 10,000 cpm group (413.7 s) compared to the 5000 cpm group (463.4 s), although there was no significant difference (p = 0.5999). One patient had an iatrogenic retinal break in the 10,000 cpm group while two patients had an iatrogenic retinal break in the 5000 cpm group. The time for posterior vitreous detachment (PVD) induction and the number of instruments used were not significantly different between the two groups. CONCLUSION: The difference in vitrectomy times between the 10,000 cpm vitrectomy probe and the 5000 cpm cutter were not statistically significant. This may suggest that other factors affect efficiency rather than the limitations of equipment.

SRSF5 Regulates the Expression of BQ323636.1 to Modulate Tamoxifen Resistance in ER-Positive Breast Cancer.

About 70% of breast cancer patients are oestrogen receptor-positive (ER +ve). Adjuvant endocrine therapy using tamoxifen (TAM) is an effective approach for preventing local recurrence and metastasis. However, around half of the patients will eventually develop resistance. Overexpression of BQ323636.1 (BQ) is one of the mechanisms that confer TAM resistance. BQ is an alternative splice variant of NCOR2. The inclusion of exon 11 generates mRNA for NCOR2, while the exclusion of exon 11 produces mRNA for BQ. The expression of SRSF5 is low in TAM-resistant breast cancer cells. Modulation of SRSF5 can affect the alternative splicing of NCOR2 to produce BQ. In vitro and in vivo studies confirmed that the knockdown of SRSF5 enhanced BQ expression, and conferred TAM resistance; in contrast, SRSF5 overexpression reduced BQ expression and, thus, reversed TAM resistance. Clinical investigation using a tissue microarray confirmed the inverse correlation of SRSF5 and BQ. Low SRSF5 expression was associated with TAM resistance, local recurrence and metastasis. Survival analyses showed that low SRSF5 expression was associated with poorer prognosis. We showed that SRPK1 can interact with SRSF5 to phosphorylate it. Inhibition of SRPK1 by a small inhibitor, SRPKIN-1, suppressed the phosphorylation of SRSF5. This enhanced the proportion of SRSF5 interacting with exon 11 of NCOR2, reducing the production of BQ mRNA. As expected, SRPKIN-1 reduced TAM resistance. Our study confirms that SRSF5 is essential for BQ expression. Modulating the activity of SRSF5 in ER +ve breast cancer will be a potential approach to combating TAM resistance.

Recurrence patterns among patients with sinonasal mucosal melanoma: A multi-institutional study.

OBJECTIVE: To evaluate recurrence patterns and survival after recurrence among patients with sinonasal mucosal melanoma (SNMM). METHODS: This was a multi-institutional retrospective review from seven U.S. institutions of patients with SNMM from 1991 to 2022. Recurrence was categorized as local, regional, distant, or multifocal. Kaplan-Meier tests were used to evaluate disease-free survival (DFS), overall survival (OS), and post-recurrence survival (PRS) reported with standard errors (SE) and log-rank testing used for comparison. Cox-regression was further used, with hazard ratios (HR) and 95% confidence intervals (CI) reported. RESULTS: Among 196 patients with SNMM, there were 146 patients with recurrence (74.5%). Among all patients, 60-month DFS (SE) was 15.5% (2.9%), 60-month OS (SE) was 44.7% (3.7%), mean age ± standard deviation at diagnosis was 69.7 ± 12.5 years, and 54.6% were female. In 26 patients who underwent primary treatment of the neck, 60-month DFS did not differ from no treatment (p > 0.05). Isolated distant recurrence was most common (42.8%), followed by local (28.3%), multifocal (20.7%), and regional recurrence (8.3%). Among patients with regional recurrence in the neck, there was no 60-month PRS benefit for patients undergoing salvage neck dissection or radiation (p > 0.05). Among patients with distant recurrence, only immunotherapy was associated with improved 12-month PRS (HR = 0.32, 95% CI = 0.11-0.92, p = 0.034), and no treatment group was associated with improved 24- or 60-month PRS (p > 0.05). CONCLUSION: SNMM is associated with a high recurrence rate and poor survival. Primary treatment of the neck was not associated with reduced recurrence, and immunotherapy for treatment of distant recurrence was associated with increased 12-month PRS.

mTOR Signalling Pathway: A Potential Therapeutic Target for Ocular Neurodegenerative Diseases.

Recent advances in the research of the mammalian target of the rapamycin (mTOR) signalling pathway demonstrated that mTOR is a robust therapeutic target for ocular degenerative diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. Although the exact mechanisms of individual ocular degenerative diseases are unclear, they share several common pathological processes, increased and prolonged oxidative stress in particular, which leads to functional and morphological impairment in photoreceptors, retinal ganglion cells (RGCs), or retinal pigment epithelium (RPE). mTOR not only modulates oxidative stress but is also affected by reactive oxygen species (ROS) activation. It is essential to understand the complicated relationship between the mTOR pathway and oxidative stress before its application in the treatment of retinal degeneration. Indeed, the substantial role of mTOR-mediated autophagy in the pathogenies of ocular degenerative diseases should be noted. In reviewing the latest studies, this article summarised the application of rapamycin, an mTOR signalling pathway inhibitor, in different retinal disease models, providing insight into the mechanism of rapamycin in the treatment of retinal neurodegeneration under oxidative stress. Besides basic research, this review also summarised and updated the results of the latest clinical trials of rapamycin in ocular neurodegenerative diseases. In combining the current basic and clinical research results, we provided a more complete picture of mTOR as a potential therapeutic target for ocular neurodegenerative diseases.

The role of anti-vascular endothelial growth factor in treatment of retinopathy of prematurity-a current review.

The review aims to evaluate the uses of conventional laser therapy and intravitreal injection of various anti-VEGF in terms of efficacy and side effects for the treatment of retinopathy of prematurity. A literature search of the publication, concerning conventional laser treatment and intravitreal injection of anti-VEGF for ROP. A total of 40 articles were reviewed after curation by the authors for relevance. Intravitreal anti-VEGF showed better ocular efficacy in zone I ROP while laser therapy had a lower recurrence rate in zone II. Comparing the two mainstay anti-VEGF agents, bevacizumab showed lower ROP recurrence rate than ranibizumab. Anti-VEGF has a higher chance in developing persistent peripheral avascularisation compared to conventional laser therapy, but a lower chance of developing high myopia. Ranibizumab has a lower systemic absorption than bevacizumab, despite having no difference in the incidence of persistent peripheral avascularisation. In conclusion, it is advised that intravitreal anti-VEGF should be used as the first-line treatment for zone I ROP while laser therapy should be the mainstay for zone II ROP owing to the different pathogenetic mechanisms. In patients with recurrence after initial anti-VEGF injection, that given ranibizumab may opt to repeat the injection while that given bevacizumab should consider supplement laser ablative treatment.

Management of Patients with Newly Diagnosed Diabetic Mellitus: Ophthalmologic Outcomes in Intensive versus Conventional Glycemic Control.

BACKGROUND AND OBJECTIVE: Diabetic retinopathy, a microvascular complication of diabetes mellitus, is one of the most important causes of visual loss in developed countries. Our objective is to evaluate the efficacy of intensive versus conventional glycemic control of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients in terms of ophthalmologic outcome, pathogenesis of the early worsening of diabetic retinopathy, risk factors for early worsening and diabetic retinopathy progression. METHODS: A literature search on publications concerning glycaemic control in diabetic retinopathy and management of newly diagnosed diabetes mellitus by intensive versus conventional glycaemic control. RESULTS: A total of 22 articles were reviewed after curation by the authors for relevance. Nineteen articles are randomized control trial, 2 articles are observational studies and 1 is clinical trial. Fifteen articles investigated the glycaemic control in T1DM-related diabetic retinopathy and 8 on T2DM-related diabetic retinopathy. The level of glycemia (in terms of HbA1c level) is significantly related to the diabetic retinopathy progression in both T1DM and T2DM. Intensive glycemic control was found to reduce the development of severe diabetic retinopathy, including severe non-proliferative diabetic retinopathy, neovascularization, clinically significant macular edema and loss of vision. Early worsening of diabetic retinopathy commonly occurs during the first year of intensive treatment, especially those initially present with proliferative or severe non-proliferative retinopathy. However, most patients with early worsening can recover and their long-term ophthalmologic outcomes are better when compared to conventional glycemic control. CONCLUSION: The current guideline on HbA1c level is considered sufficient for the minimization of diabetic retinopathy progression. More frequent monitoring for early worsening should be recommended for newly diagnosed diabetes cases already presenting with retinopathy.

Treatment of large, chronic and persistent macular hole with internal limiting membrane transposition and tuck technique.

BACKGROUND: Large, chronic full thickness macular holes which failed previous treatments are difficult to manage and even left untreated due to poor prognosis. A retrospective review of consecutive cases with chronic (at least 1 year) full thickness macular holes and internal limiting membrane (ILM) free flap transposition with tuck technique, after previously failed vitrectomy. METHODS: This was a retrospective and interventional study conducted in a single centre by a single surgeon. Patients with full thickness macular hole for at least 1 year and at least one previously failed vitrectomy with ILM peeling were recruited. A 25G vitrectomy with ILM free flap transposition was done without assistance of PFCL, viscoelastic or autologous blood. The free flap was manually tucked into the macular hole free space and gas fluid exchange was performed with 20% SF6 as tamponade. The patients were postured prone for 2 weeks postoperatively. Best corrected visual acuity, macular hole duration, previous surgeries, optical coherence tomography (OCT) appearance, hole size and closure rate were recorded. RESULTS: 8 consecutive patients were included from May 2016 to Feb 2018. Transposition surgery was performed an average of 1481 days (SD 1096) after diagnosis of macular hole and average of 1226 days (SD 1242) after first vitrectomy. Macular hole mean size was 821 µm (SD 361.3), preoperative VA was logMAR 1.038 (SD 0.19), postoperative VA was logMAR 0.69 (SD 0.19) at 3 months. There were 1.13 lines gained and a significant improvement of logMAR 0.33 (p = 0.0084) at 6 months. Hole closure was seen in 7 out of 8 eyes (87.5%). The OCT with failed closure showed ILM flap within a flat hole, however no overlying neurosensory layers was seen. The duration from diagnosis to surgery was 2349 days in this case. CONCLUSION: Free flap ILM transposition tuck without the use of additional intraoperative tamponade is an effective technique in treating large chronic macular holes with previously failed primary macular hole surgeries.Trial registration (IRB of the Hong Kong University and Hospital Authority Hong Kong West Cluster, ref UW19-440), June 17, 2019.