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To assess the predictive value of the tumor staging system in the AJCC Cancer Staging Manual, Eighth Edition, and histologic features for outcomes and metastasis patterns in conjunctival melanoma (CM).Retrospective, single-center cohort study.Eighty-three patients with CM were treated at Shanghai Ninth People's Hospital between 2000 and 2021.We reviewed the clinical and histologic parameters and used Kaplan-Meier survival curves and Cox proportional hazards regression models for risk factor analyses.Time to nodal/distant metastasis, disease-specific survival, metastatic pattern, and metastatic site.At presentation, 5 patients (6%) had clinical tumor (cT)1 disease, 34 patients (41%) had cT2 disease, and 44 patients (53%) had cT3 disease. Four patients (5%) had nodal metastasis (N1), and none had distant metastasis (M1). During follow-up, 12 patients (14%) developed nodal metastasis, 29 patients (35%) developed distant metastasis, and 26 patients (31%) died of disease. The brain, liver, and lung were common distant metastasis sites. Higher cT category was associated with increased risks of distant metastasis (P0.001) and disease-specific death (P = 0.002). The separate analysis of primary and recurrent tumors at presentation showed that the patients with cT3 tumors had a higher risk of distant metastasis than those with cT2 tumors. Greater tumor thickness, ulceration, and the presence of regression were correlated with distant metastasis. Previously unreported mutations were detected in the tumor suppressor genes FAT atypical cadherin 4 (FAT4) and spleen associated tyrosine kinase (SYK). Among the 29 patients who developed distant metastasis, we analyzed 2 patterns of metastasis: Eleven patients (38%) developed nodal metastasis before distant metastasis, and 18 patients (62%) developed distant metastasis without previously known nodal metastasis. The patients with cT3 tumors were more likely to follow the latter metastasis pattern (P = 0.02).Conjunctival melanoma presented with mostly advanced stages and high rates of distant metastasis in the current Chinese cohort. This study confirmed the prognostic value of the tumor staging system in the AJCC Cancer Staging Manual, Eighth Edition, for Chinese patients. Histologic features, such as tumor thickness and ulceration, should be emphasized when assessing prognosis and guiding the treatment of CM.

To identify the risk factors of orbital exenteration and to evaluate the prognosis of exenterated patients with conjunctival melanoma (CM).79 consecutive CM patients treated at our centre from January 2000 to September 2021 were included. The demographic, clinical and pathological characteristics were compared between eye-sparing patients and orbital exenteration patients. Main outcomes including progression-free survival (PFS), distant metastasis-free survival (DFS) and disease specific survival (DSS) were assessed in exenterated patients.The mean follow-up period was 46 ± 39 months. Risk factors for orbital exenteration were identified as worse cT category (OR, 50.75; 95% CI, 5.40-477.07; P = 0.001) and greater tumour thickness (OR, 1.27; CI, 1.04-1.55; P = 0.02). Of the 32 patients who underwent orbital exenteration, three (9.4%) had local recurrence; six (18.8%) experienced regional metastasis; sixteen (50.0%) suffered distant metastasis and fifteen (46.9%) died of metastatic disease. In patients who received orbital exenteration, palpebral conjunctiva involvement (PFS: P 0.01; DFS: P 0.05; DSS: P = 0.04), histological ulceration (PFS: P = 0.03; DFS: P = 0.01; DSS: P = 0.03) and regression (PFS: P = 0.01; DFS: P 0.01; DSS: P = 0.04) were identified as risk factors for poor prognosis. Caruncle involvement (P = 0.01) was also associated with increased risk of melanoma related mortality in exenterated patients.Histopathological factors should be taken into account when formulating surgical plans for orbital exenteration and when evaluating patients' prognosis following exenteration. For CM patients with caruncle or palpebral conjunctiva involvement, orbital exenteration should be considered for unresectable disease.

Unlike cutaneous melanoma, uveal melanoma (UM) is characterized by mutations in GNAQ and GNA11 and remains a fatal disease because there is essentially no effective targeted therapy or immunotherapy available. We report the discovery of the copper ionophore elesclomol as a GNAQ/11-specific UM inhibitor. Elesclomol was identified in a differential cytotoxicity screen of an in-house tool compound library, and its in vivo pharmacological efficacy was further confirmed in zebrafish and mouse UM models. Mechanistically, elesclomol transports copper to mitochondria and produces a large amount of reactive oxygen species (ROS) as Cu(II) is reduced to Cu(I) in GNAQ/11-mutant UM cells, which selectively activates LATS1 kinase in the Hippo signaling pathway and consequently promotes YAP phosphorylation and inhibits its nuclear accumulation. The inactivation of YAP downregulates the expression of SNAI2, which in turn suppresses the migration of UM cells. These findings were cross validated by our clinical observation that YAP activation was found specifically in UM samples with a GNAQ/11 mutation. Furthermore, addition of binimetinib, a MEK inhibitor, to elesclomol increased its synthetic lethality to GNAQ/11-mutant UM cells, thereby overriding drug resistance. This effect was confirmed in an orthotopic xenograft model and in a patient-derived xenograft model of UM. These studies reveal a novel mechanistic basis for repurposing elesclomol by showing that copper homeostasis is a GNAQ/11-specific vulnerability in UM. Elesclomol may provide a new therapeutic path for selectively targeting malignant GNAQ/11-mutant UM.

The differential diagnosis of eyelid basal cell carcinoma (BCC) and sebaceous carcinoma (SC) is highly dependent on pathologist's experience. Herein, we proposed a fully automated differential diagnostic method, which used deep learning (DL) to accurately classify eyelid BCC and SC based on whole slide images (WSIs).We used 116 haematoxylin and eosin (HE)-stained sections from 116 eyelid BCC patients and 180 HE-stained sections from 129 eyelid SC patients treated at the Shanghai Ninth People's Hospital from 2017 to 2019. The method comprises two stages: patch prediction by the DenseNet-161 architecture-based DL model and WSI differentiation by an average-probability strategy-based integration module, and its differential performance was assessed by the carcinoma differentiation accuracy and F1 score. We compared the classification performance of the method with that of three pathologists, two junior and one senior. To validate the auxiliary value of the method, we compared the pathologists' BCC and SC classification with and without the assistance of our proposed method.Our proposed method achieved an accuracy of 0.983, significantly higher than that of the three pathologists (0.644 and 0.729 for the two junior pathologists and 0.831 for the senior pathologist). With the method's assistance, the pathologists' accuracy increased significantly (P0.05), by 28.8% and 15.2%, respectively, for the two junior pathologists and by 11.8% for the senior pathologist.Our proposed method accurately classifies eyelid BCC and SC and effectively improves the diagnostic accuracy of pathologists. It may therefore facilitate the development of appropriate and timely therapeutic plans.

Ocular adnexal sebaceous carcinoma (OASeC) is an aggressive eyelid carcinoma. Analysis of molecular-genetic drivers of this disease could reveal new prognostic markers and actionable targets for treatment. To identify somatically acquired genomic mutations in OASeC and explore their associations with metastasis, whole-exome sequencing on DNA extracted from retrospectively collected tumor samples was performed. Thirty-one patients in two orbital oncology centers with OASeC were included. Sequencing results were analyzed to detect mutations and explore their possible association with metastasis. The median patient age was 64 years. A total of 1780 candidate somatic mutations were identified with median mutation rate of 1.0/Mb (range, 0.2-13.6). The five most commonly mutated genes (as determined by MutSig; q value < 0.25) were TP53 (mutated in 22 cases), ZNF750 (13 cases), RB1 (12 cases), NOTCH1 (8 cases), and PCDH15 (5 cases). Mutations in ZNF750 or NOTCH1 pathway genes were present in 24 (77%) of the 31 cases; there was a trend toward mutual exclusivity of ZNF750 and NOTCH1 mutations. All eight tumors with NOTCH1 mutations also had TP53 and/or RB1 mutations. Four of the five PCDH15 mutations and all four PCDH15 missense mutations were identified in patients with metastatic disease, including one patient with distant metastasis and three with nodal metastasis. PCDH15 was significantly associated with metastasis (P = 0.01). We identified the most commonly mutated genes in a series of OASeCs and found a previously unreported mutation in OASeC, PCDH15 mutation, that was significantly associated with metastasis. NOTCH1 mutation is an actionable mutation; clinical trials targeting this mutation are available throughout the US and could be considered for patients with metastatic NOTCH1-mutant OASeC. TP53, ZNF750, RB1, and PCDH15 mutations are most likely loss-of-function mutations and may have diagnostic and prognostic importance.

BackgroundMetastasis dominates the prognosis of eyelid sebaceous carcinoma (SC). This study aimed to explore risk factors for nodal metastasis and develop a nomogram to predict nodal metastasis in patients with eyelid SC.MethodsA retrospective case–control study was performed, comprising 320 patients with eyelid SC. Cox analyses were employed to investigate predictors of metastasis-free survival (MFS), and a nomogram was established and validated by the bootstrap method.ResultsForty patients (12.5%) developed nodal metastasis during a median follow-up of 48.0 months, and the median period between the initial treatment and first nodal metastasis was 18.5 months (range 6.0–80.0 months). The 1-year, 3-year and 5-year nodal metastasis rates were 5.5%, 12.5% and 15.4%, respectively. Diffuse pattern (HR: 4.34, 95% CI 1.75 to 10.76, p=0.002), orbital invasion at presentation (HR: 3.22, 95% CI 1.42 to 7.33, p=0.005), perineural invasion (HR: 3.24, 95% CI 1.11 to 9.49, p=0.032) and high Ki-67 percentage (HR: 1.03, 95% CI 1.01 to 1.05, pConclusionsWe identified risk factors for nodal metastasis and developed a nomogram to provide individualised estimates of nodal metastasis for eyelid SC patients and guide postoperative management. This nomogram contained clinicopathological factors besides the T category of the TNM staging system and suggesting great clinical value.

Identifying tumor characteristics that correlate with metastasis and survival in patients with conjunctival melanoma can potentially lead to better outcomes through a better selection of patients for adjuvant treatments including potentially life-saving new melanoma therapy. The objective of this study was to validate the conjunctival melanoma staging criteria in the American Joint Committee on Cancer (AJCC) Cancer Staging Manual (8th edition) and explore the prognostic importance of tumor thickness, histologic ulceration, and sentinel lymph node biopsy (SLNB) findings in patients with conjunctival melanoma. This is a case series of 88 consecutive patients with conjunctival melanoma. Clinicopathologic characteristics were analyzed. Associations between pathologic characteristics and outcomes were studied using Kaplan-Meier survival analysis. Local recurrence, lymph node metastasis, distant metastasis, and disease-specific survival (DSS) were the main outcome measures. The study included 56 women and 32 men; the median age was 62 years. At presentation, 41 patients had T1 disease, 23 had T2 disease, 23 had T3, and 1 had T4 disease. Sixty-six patients had invasive conjunctival melanoma (median thickness, 1.56 mm), 17 had conjunctival melanoma in situ, and in 5 patients, tumor thickness could not be determined. Overall, 22 patients had ulceration. In total, 31 patients underwent SLNB, and 4 had a positive sentinel lymph node (SLN). The median follow-up time was 46.6 months. Overall, 12 patients had nodal metastasis at presentation or during follow-up, 19 patients had distant metastasis at last follow-up, and 14 patients died of the disease. Tumor thickness and ulceration were associated with increased risks of nodal metastasis, distant metastasis, and death from the disease. Overall, greater clinical T category at presentation was associated with increased risks of distant metastasis and disease-related death; however, the risks of distant metastasis and disease-related death did not differ between T1 (bulbar) and T2 (nonbulbar) tumors or between T2c,d (caruncular) and T1-T2a,b (noncaruncular) tumors. In patients who underwent SLNB, a positive SLN was associated with worse distant metastasis free survival and DSS. Consideration should be given to adding ulceration and emphasizing tumor thickness as the main determinants of pathologic T category for conjunctival melanoma in future AJCC classifications. The significant association between a positive SLN and worse DSS highlights the importance of SLNB for prognosis in patients with conjunctival melanoma and selecting high-risk patients for adjuvant drug treatment.

PURPOSE: Information regarding risk of metastasis and disease-related death (DD) from conjunctival squamous cell carcinoma (SCC) is relatively scarce. We explored prognostic factors for orbital exenteration, local recurrence, nodal metastasis, and DD in patients with conjunctival SCC. DESIGN: Retrospective cross-sectional study. METHODS: All consecutive patients with conjunctival SCC treated by the senior author at MD Anderson Cancer Center during1999–2018 were included. Survival curves were estimated using the Kaplan-Meier method, and survival differences were assessed using 2-sided log-rank tests. RESULTS: The study included 44 patients (24 men;20 women); median age was 64 years (range, 40–90). T categories at presentation were as follows: Tis, 20 patients; T2, 8; T3, 9; and T4, 7. Eighteen patients (41%) had tumors exclusively in the bulbar conjunctiva; 26(59%) had non-bulbar conjunctival involvement. The median follow-up time was 29.2 months (95% CI: 21.8–44.3). Orbital exenteration was performed in 10 cases (23%) and was associated with T3 or more advanced disease at presentation (p

BackgroundThe clinical and pathological risk factors for worse T stage and prognosis in eyelid and periocular squamous cell carcinomas (SCCs) remain unclear. P63 was reported to predict a worse prognosis in other SCCs; however, this correlation was not validated in eyelid and periocular SCCs.MethodsWe reported on a retrospective case series of 85 consecutive patients with eyelid and periocular SCCs from 1995 to 2019. Cox proportional hazards regression models and logistic regression models were applied for risk factor analysis.ResultsThirty-nine (45.8%) patients were diagnosed with T4 SCCs. Four (5.1%) patients developed nodal metastasis, and five (6.4%) patients developed distant metastasis during the follow-up. 2-year and 5-year disease-specific survival rates were 95.3% and 86.4%, respectively. Poorly or moderately differentiated eyelid and periocular SCCs were associated with worse T stage (p=0.001; p=0.008). Poor differentiation was associated with a higher risk of recurrence (p=0.024). Disease-specific death was more common in patients with T4 stage SCCs (p=0.038, HR=9.05). P63 expression was more common in patients with T3c or worse stage (p=0.008, OR=3.77). P63 expression alone was associated with worse differentiation (p=0.029), higher risk of perineural invasion (p=0.042, OR=4.61) and metastasis (p=0.009, HR=3.99). P63 expression (p=0.012, HR=7.80), coexpression of P63 and Ki67 (p=0.007, HR=9.21) and distant metastasis (p=0.001, HR=11.23) were associated with disease-specific death.ConclusionPatients presented with more aggressive orbital invasion features and a higher rate of distant metastasis in this cohort. P63 and coexpression of Ki67 predicted a worse stage, differentiation and prognosis, including metastasis and death due to disease.

Background/aimsTo validate the predictive value of the American Joint Committee on Cancer (AJCC) 8th-edition classification for local recurrence, metastasis and survival in patients with eyelid sebaceous carcinoma.MethodsWe performed a retrospective review of 100 consecutive patients with eyelid sebaceous carcinoma. Eyelid carcinomas were staged according to the AJCC 7th-edition and 8th-edition criteria. Associations between T and N categories and disease-related outcomes including local recurrence, lymph node metastasis, distant metastasis and survival were evaluated.Results60 women and 40 men had a median age of 67 years (range, 41–94 years). The proportions of patients who experienced local recurrence, lymph node metastasis, distant metastasis and death from disease were 6%, 21%, 7% and 6%, respectively. Two-year and 5-year disease-specific survival (DSS) rates were 93.8% and 92.0%, respectively. There were significant correlations between (1) T2c or worse category and lymph node metastasis (p=0.04) and distant metastasis (p=0.01), (2) T3b or worse category and local recurrence (p=0.01) and death from disease (p=0.01) and (3) N1 category at presentation and distant metastasis (pConclusionsT and N categories per AJCC 8th-edition classification are predictive of local recurrence, metastasis and DSS outcomes for eyelid sebaceous carcinoma. Surgeons should perform strict surveillance testing for nodal and systemic metastases in patients with T2c or worse T category and/or N1 disease at presentation.

Ocular adnexal sebaceous carcinoma (OASeC) is an aggressive eyelid carcinoma. Analysis of molecular-genetic drivers of this disease could reveal new prognostic markers and actionable targets for treatment. To identify somatically acquired genomic mutations in OASeC and explore their associations with metastasis, whole-exome sequencing on DNA extracted from retrospectively collected tumor samples was performed. Thirty-one patients in two orbital oncology centers with OASeC were included. Sequencing results were analyzed to detect mutations and explore their possible association with metastasis. The median patient age was 64 years. A total of 1780 candidate somatic mutations were identified with median mutation rate of 1.0/Mb (range, 0.2-13.6). The five most commonly mutated genes (as determined by MutSig; q value 0.25) were TP53 (mutated in 22 cases), ZNF750 (13 cases), RB1 (12 cases), NOTCH1 (8 cases), and PCDH15 (5 cases). Mutations in ZNF750 or NOTCH1 pathway genes were present in 24 (77%) of the 31 cases; there was a trend toward mutual exclusivity of ZNF750 and NOTCH1 mutations. All eight tumors with NOTCH1 mutations also had TP53 and/or RB1 mutations. Four of the five PCDH15 mutations and all four PCDH15 missense mutations were identified in patients with metastatic disease, including one patient with distant metastasis and three with nodal metastasis. PCDH15 was significantly associated with metastasis (P = 0.01). We identified the most commonly mutated genes in a series of OASeCs and found a previously unreported mutation in OASeC, PCDH15 mutation, that was significantly associated with metastasis. NOTCH1 mutation is an actionable mutation; clinical trials targeting this mutation are available throughout the US and could be considered for patients with metastatic NOTCH1-mutant OASeC. TP53, ZNF750, RB1, and PCDH15 mutations are most likely loss-of-function mutations and may have diagnostic and prognostic importance.

The present study aimed to investigate the efficacy of tailored treatment for the management of scleral necrosis following pterygium surgery. A series of nine cases of scleral necrosis following pterygium excision between September 2009 and September 2012 were included. In cases where ischemia was the cause of scleral necrosis, Tenon's membrane covering (TMC) surgery was performed. For cases with surgically-induced necrotizing scleritis (SINS), systemic immunosuppressive therapy following surgical repair of the scleral defect was administered in the form of oral prednisolone (starting dose, 30-60 mg/day). Five patients with ischemic scleral necrosis received TMC postoperatively. Four patients with SINS received various doses of oral prednisolone according to their systematic immune state. All patients had successful postoperative results except one with rheumatoid arthritis, who postoperatively developed scleral patch graft melting within 2 weeks. Following aggressive immunosuppressive treatment, the scleral patch graft was saved. In conclusion, patients achieved positive results using tailored treatment according to the pathogenesis of their scleral necrosis.

Melanoma is an extremely aggressive disease with rapid progression, high metastatic potential and recurrence. Simultaneous correction of multiple tumor-specific gene abnormalities has become an attractive approach for developing therapeutics to treat melanoma. To potentiate anti-melanoma activity, we tested a "domino effect-like" therapeutic approach by uniquely targeting one defect and automatically triggering the endogenous corrections of other defects. Using this strategy, in a suspicious INK4b-ARF-INK4a gene cluster at chromosome 9p21, aberrant INK4a and INK4b defects were simultaneously endogenously auto-corrected after targeting the suppression of abnormal ANRIL lncRNA. In cell culture, this treatment significantly reduced the tumor metastatic capacity and tumor formation compared with absence of treatment. In animals harboring tumor xenografts, this therapeutic approach significantly inhibited tumor growth and reduced the tumor weight. Our results reveal a novel therapeutic strategy that significantly potentiates anti-melanoma efficiency by reprogramming the aberrant INK4-hub.

Uveal melanoma (UM) is the most common form of primary intraocular malignancy in adult and has the tendency to metastasize. BAP1 mutations are frequently found in UM and are associated with a poor prognosis. The role of BAP1 in cell cycle regulation is currently a research highlight, but its underlying mechanism is not well understood. Here, we report that BAP1 knockdown can lead to G1 arrest and is accompanied by a decrease in the expression of S phase genes in OCM1 cells. Furthermore, in chromatin immunoprecipitation experiments, BAP1 could bind to E2F1 responsive promoters and the localization of BAP1 to E2F1-responsive promoters is host cell factor-1 dependent. Moreover, BAP1 knockdown leads to increased H2AK119ub1 levels on E2F responsive promoters. Together, these results provide new insight into the mechanisms of BAP1 in cell cycle regulation.

Primary orbital arteriovenous malformations are a rare kind of vascular malformation lesions. The authors present a 17-year-old man presented with swelling and pulsation in the left upper eyelid. The angiogram of the left internal carotid artery showed that arteriovenous malformations at the left upper eyelid area were supplied with one of the branches of ophthalmic artery. In this report, the authors elaborated the comprehensive treatments of primary arteriovenous malformation.

Increasing evidence suggests that aberrant long non-coding RNAs (lncRNAs) are significantly correlated with the pathogenesis, development and metastasis of cancers. RHPN1 antisense RNA 1 (RHPN1-AS1) is a 2030-bp transcript originating from human chromosome 8q24. However, the role of RHPN1-AS1 in uveal melanoma (UM) remains to be clarified. In this study, we aimed to elucidate the molecular function of RHPN1-AS1 in UM. The RNA levels of RHPN1-AS1 in UM cell lines were examined using the quantitative real-time polymerase chain reaction (qRT-PCR). Short interfering RNAs (siRNAs) were designed to quench RHPN1-AS1 expression, and UM cells stably expressing short hairpin (sh) RHPN1-AS1 were established. Next, the cell proliferation and migration abilities were determined using a colony formation assay and a transwell migration/invasion assay. A tumor xenograft model in nude mice was established to confirm the function of RHPN1-AS1 in vivo. RHPN1-AS1 was significantly upregulated in a number of UM cell lines compared with the normal human retinal pigment epithelium (RPE) cell line. RHPN1-AS1 knockdown significantly inhibited UM cell proliferation and migration in vitro and in vivo. Our data suggest that RHPN1-AS1 could be an oncoRNA in UM, which may serve as a candidate prognostic biomarker and target for new therapies in malignant UM.

Importance To our knowledge, there are no validation studies to date of the prognostic value of theAJCC Cancer Staging Manual, eighth edition (AJCC 8), criteria for eyelid and periocular squamous cell carcinoma. Objective To determine the association of tumor (T) category inAJCC 8 with local recurrence, nodal metastasis, distant metastasis, and disease-specific survival (DSS) for eyelid and periocular squamous cell carcinoma. Design, Setting, and Participants In this retrospective, single-center cohort study, 109 consecutive patients with eyelid and periocular squamous cell carcinoma treated from January 1999 to April 2018 were included. Patients with secondary involvement of the periocular region were excluded. Main Outcomes and Measures Local recurrence, nodal metastasis, distance metastasis, and DSS. Results Of the 109 included patients, 81 (74.3%) were male, and the median (range) age was 66 (40-91) years. At presentation, 43 patients (39.4%) had recurrent tumor, 4 (3.7%) had nodal metastasis, and 1 (0.9%) had distant metastasis. The median (range) follow-up was 23 (1-161) months. During follow-up, 11 patients (10.1%) developed local recurrence, 7 (6.4%) developed nodal metastasis, 2 (1.8%) developed distant metastasis, and 9 (8.3%) died of disease. The 5-year DSS rate was 87.7% (95% CI, 79.5-96.9). Chronic immunosuppression (hazard ratio, 47.24; 95% CI, 7.33-304.30;P Conclusions and Relevance These findings suggest that T category inAJCC 8 is associated with nodal metastasis and DSS. Immunosuppression and presentation with recurrent disease are associated with increased risk of future local recurrence. Patients with tumors of clinical stage T2c or worse at presentation are at increased risk of nodal metastasis and worse DSS and should undergo surveillance for nodal metastasis. Future studies, ideally prospective in design, could provide greater confidence in these findings.

Aim The aim of this study was to compare the efficacy and safety of propranolol versus corticosteroids for the treatment of periorbital infantile haemangiomas (IHs). Methods A literature review using PubMed, Ovid Medline, EBSCO, Springer, Web of Knowledge, Cochrane Library, CNKI and associated references before 2 March 2013 was conducted. The main outcomes were distribution of locations, response rate, rebound growth rate, spherical and cylinder power before and after treatment, amblyopia rate and adverse events. Results Thirty-one studies including 425 patients met the inclusion criteria. A total of 70.6% of patients were female, 89.6% of the periorbital IHs were located in the upper or lower eyelid area. The most common administration routes involved oral propranolol and intralesional injection of corticosteroids. The mean response rate was 94.0% for propranolol and 82.3% for corticosteroid (P = 0.001). The rebound growth rate was 13.9% for propranolol and 12.0% for steroids (P = 0.71). Astigmatism was reduced in both propranolol and steroid studies (P < 0.0001, P < 0.0001), but a significant reduction in spherical power was only demonstrated in propranolol studies (P = 0.005). A total of 31.1% of patients treated with corticosteroids developed post-operative amblyopia compared with 16.7% of patients treated with propranolol (P = 0.04). Oral propranolol seemed to induce more temporary adverse events than intralesional corticosteroids administration (24.0% vs. 9.6%, P = 0.006). Conclusion Propranolol may represent an effective therapy for periorbital IHs compared with the use of corticosteroids; however, further randomised control studies are needed to compare adverse events.

Low-flow orbital or periorbital venous malformation (OVM) is the most common periorbital vascular lesion that may produce an appearance defect, visual dysfunction, internal hemorrhage, and thrombosis. Intralesional injection of pingyangmycin as a minimally invasive, gentle intervention may have better outcomes in treating low-flow OVMs compared with other currently used methods.To investigate the efficacy and safety of intralesional injection of pingyangmycin for treatment of low-flow OVM.A retrospective, noncomparative, interventional case series was conducted in a single medical center. Thirty-three consecutive patients with low-flow OVMs undergoing intralesional injection of pingyangmycin were included in the study.Injections of 1 to 5 mL of a pingyangmycin 1.5-mg/mL mixture with lidocaine hydrochloride, 2%, were given. Each patient received 1 to 4 injections at an interval of 6 to 8 weeks between February 2002 and January 2013. Mixture volume was determined on a basis of 0.5 mL of solution per cubic centimeter of the lesion. The maximum dose for 1 injection was 8 mg. Clinical observations were well documented before and after treatment.Reduction of lesion volume based on ultrasound-measured volume; overall appearance, including blue color and thickness of lesions before and after treatment; and adverse events were evaluated.Patients received a median of 2 (range, 1-4) intralesional injections of pingyangmycin. The mean pretreatment volume was 4.4 cm3 and posttreatment volume was 1.0 cm3 (t = 4.63; P.001), with a mean decrease of 84% (range, 28%-100%). Marked to moderate improvement in the volume of the lesions was noticed in 31 eyes (94%; 25 of 33 [76%] with marked improvement and 6 of 33 [18%] with moderate improvement). Improvement occurred in 95% (18 of 19) of superficial lesions, 100% (3 of 3) of deep lesions, and 91% (10 of 11) of combined lesions. We noticed significant improvements in blue color and thickness on the basis of investigator scores from clinical photographs taken before and after treatment. None of the patients had recurrence noted at their final follow-up. Adverse events were limited to swelling of the conjunctiva and localized subcutaneous atrophy.The results of intralesional pingyangmycin injection for treatment of low-flow OVM are encouraging and associated with a low risk of adverse events.

China's fisheries industry has undergone significant development in recent years. In this paper, a valuable source of information on present aquatic product production, processing methods and practices is being provided, and is supported by adequate statistical data. Inland and marine aquaculture have substantially increased fish and shellfish production in the past few years, and modern technologies employed for aquatic product processing are emphasised.

The aim of this study was to compare the efficacy and safety of propranolol versus corticosteroids for the treatment of periorbital infantile haemangiomas (IHs).A literature review using PubMed, Ovid Medline, EBSCO, Springer, Web of Knowledge, Cochrane Library, CNKI and associated references before 2 March 2013 was conducted. The main outcomes were distribution of locations, response rate, rebound growth rate, spherical and cylinder power before and after treatment, amblyopia rate and adverse events.Thirty-one studies including 425 patients met the inclusion criteria. A total of 70.6% of patients were female, 89.6% of the periorbital IHs were located in the upper or lower eyelid area. The most common administration routes involved oral propranolol and intralesional injection of corticosteroids. The mean response rate was 94.0% for propranolol and 82.3% for corticosteroid (P = 0.001). The rebound growth rate was 13.9% for propranolol and 12.0% for steroids (P = 0.71). Astigmatism was reduced in both propranolol and steroid studies (P0.0001, P0.0001), but a significant reduction in spherical power was only demonstrated in propranolol studies (P = 0.005). A total of 31.1% of patients treated with corticosteroids developed post-operative amblyopia compared with 16.7% of patients treated with propranolol (P = 0.04). Oral propranolol seemed to induce more temporary adverse events than intralesional corticosteroids administration (24.0% vs. 9.6%, P = 0.006).Propranolol may represent an effective therapy for periorbital IHs compared with the use of corticosteroids; however, further randomised control studies are needed to compare adverse events.

HIV-1-associated ocular complications, such as microvasculopathies, can lead to the loss of vision in HIV-1-infected patients. Even in patients under highly active antiretroviral therapy, ocular lesions are unavoidable. Ocular complications have been demonstrated to be closely related to the breakdown of the blood-retinal-barrier (BRB); however, the underlying mechanism is not clear. The data from this study indicated that the HIV-1 Tat protein induced the apoptosis of human retinal microvascular endothelial cells (HRMECs) and retinal pigmen epithelium (RPE) cells, which compose the inner BRB and the outer BRB, respectively. In addition, this study found that the activation of N-methyl-D-aspartate receptors (NMDARs) was involved in the apoptosis of RPE cells, but it caused no changes in HRMECs. Furthermore, both cell types exhibited enhanced expression of Bak, Bax and Cytochrome c. The inhibition of Tat activity protected against the apoptosis induced by NMDAR activation and prevented the dysregulation of Bak, Bax and Cytochrome c, revealing an important role for the mitochondrial pathway in HIV-1 Tat-induced apoptosis. Together, these findings suggest a possible mechanism and may identify a potential therapeutic strategy for HIV-1-associated ocular complications.

The efficacy and safety of beta-blockers versus corticosteroids in the treatment of infantile hemangiomas (IHs) is controversial. This study aimed to summarize evidence described in the literature and to assess the quality of studies involving beta-blockers and corticosteroids for the treatment of cutaneous IHs. Comparative studies were collected from 15 online electronic databases, including OVID Medline, PubMed, ISI Web of Science, CENTRAL, CNKI, ChiCTR, JPCTR, CTRIndia, IranCTR, SLCTR, ISRCTRN, NLCTR, GCTR, ANCTR, ClinicalTrial. gov, and associated references. Studies without a control group were excluded, and the remaining studies were assessed by two reviewers independently using the Downs & Black scale for reported quality. The main areas assessed in the included studies were volume changes, overall improvement in appearance, eye function, and adverse events. Ten comparative studies were included with a total of 419 children. A meta-analysis was not performed due to the considerable heterogeneity across studies. Some evidence showed that beta-blockers are superior to steroids in reducing volume and improving the overall appearance of IHs, such as lightening of the color and flattening of the surface. Conclusions regarding improved eye function and adverse events were divided, and no consensus has been reached on the superiority of one treatment over another. No episodes of severe-onset asthma, hypotension, or bradycardia occurred in the beta-blocker treatment due to the rigorous exclusion of patients with contraindications. Available studies indicate that beta-blockers are an alternative option to corticosteroids for IH treatment with respect to volume shrinkage and improvement in appearance. No evidence has shown a significant difference in improved eye function and adverse events between beta-blockers and corticosteroids in the treatment of IH; indeed, there is a lack of well-designed, high-quality randomized control trials.

Age-related macular degeneration (AMD) is a major cause of irreversible blindness. Choroidal structural changes seem to be inevitable in AMD pathogenesis. Our study revealed associated choroidal microstructural changes in AMD eyes. The aim of the study was to compare choroidal microstructural changes in eyes with AMD of different stages. The study was a retrospective, cross-sectional case series. The participants comprised of 32 age-matched normal eyes as controls, and 26 fellow uninvolved eyes of intermediate/late AMD, 29 of early AMD, 28 of intermediate AMD, and 39 of late AMD. All subjects underwent comprehensive ophthalmologic examination. The choroid images, including subfoveal choroidal thickness, percentage of Sattler layer area, and en face images of the choroid, were obtained using spectral-domain optical coherence tomography. The main outcome measures were subfoveal choroidal thickness changes, percentage of Sattler layer area changes, and en face images of the choroid in AMD eyes. One hundred fifty-four eyes of 96 individuals with mean age of 67.1±9.2 years were included. The mean subfoveal choroidal thickness was 295.4 ± 56.8 μm in age-matched normal eyes, 306.7 ± 68.4 μm in fellow uninvolved eyes with AMD, 293.8 ± 80.4 μm in early AMD, 215.6 ± 80.4 μm in intermediate AMD, and 200.4 ± 66.6 μm in late AMD (F = 14.2, all P

Congenital ocular malformation may lead to failure of the development of ocular regions and visual function in the pediatric population. Orbital bones are established within the first 2 months of embryogenesis. Any abnormalities may lead to failure in development of the ocular region. In this case report, we present a newborn with congenital canthus malposition, a distorted tarsus, and mild enophthalmos caused by an embryogenesis fibroma, which although rare, can result in amblyopia. Surgical resection of the fibroma followed by orbital reconstruction of the canthus, correction of malposition and tarsus extension were performed. Twelve months and 5 years follow-up showed no recurrence and the visual acuity was 20/20 in the left eye and 16/20 in the right. The deformity of the left orbit was corrected without complications and was symmetrical with the right side. This is the first known case of children with embryonic fibroma. It is likely that early reconstruction surgery may avoid visual occlusion and ocular malformation.