Background: The periocular skin is neoplasms-prone to various benign and malignant. Periocular malignancies are more aggressive and challenging to cure and repair than those in other skin areas. In recent decades, immunotherapy has significantly advanced oncology, allowing the autoimmune system to target and destroy malignant cells. Skin malignancies, especially periocular tumors, are particularly sensitive to immunotherapy. This technique has dramatically impacted the successful treatment of challenging tumors. Main text: Extraocular cancers, including eyelid (basal cell carcinoma, squamous cell carcinoma, melanoma, merkel cell carcinoma), conjunctival tumors (conjunctival melanoma, ocular surface squamous neoplasia) and other rare tumors, are unique and challenging clinical situations. Several genetic alterations associated with the pathogenesis of these diseases have been identified, and molecular mechanism are essential for the development of the immunotherapy agents, such as Hedgehog pathway inhibitors (vismodegib and sonidegib) for basal cell carcinoma, BRAF/MEK inhibitors (vemurafenib, dabrafenib, and encorafenib) for melanoma, and immune checkpoint inhibitors (Avelumab, pembrolizumab) for Merkel cell carcinoma. Conclusions: The optimal treatment for periocular skin cancer depends on the type and size of the tumor and whether it involves orbital and adnexal structures. Adjuvant and neoadjuvant therapy with chemotherapy-targeted therapies and immune checkpoint inhibitors should be considered based on tumor type, tumor molecular profile, expected response rate, and candidacy for systemic treatment.

Background:With globalization, oculoplastic surgeons must understand the intricate morphological nuances of the periocular region across ethnicities to ensure precise treatment and avoid facial disharmony or dysfunction. Direct comparisons in two-dimensional (2D)-based periocular morphology between studies can be challenging due to the limited number of parameters and complicated variations in equipment, environments, measurement personnel, and methods. Therefore, it is imperative to explore the detailed three-dimensional (3D) periocular morphological disparities between young Caucasian and Chinese populations. This study aimed to establish gender- and ethnicity-specific 3D anthropometric data in periocular soft tissue for young Caucasian and Chinese adults and to determine the inter-racial and inter-gender differences. Methods:This descriptive, cross-sectional study enrolled 46 Asians and 101 Caucasians aged 18 to 30 years. 3D models were analyzed with 32 landmarks, yielding 21 linear distances, three curvatures, six angles, and three proportions. Comparisons were made across left and right eyes, ethnic groups, and sexes to assess ethnic disparities and sexual dimorphism. Results:Twenty-nine measurements were compared between the left and right sides revealing significant differences (P<0.002) in two measurements for Caucasian and Chinese females, respectively. However, these differences were submillimeter levels and potentially inconsequential in practical settings with left-right differences of -0.58 and -0.57 mm (P<0.001) for double-eyelid fold-palpebral margin distance (medial) (FPDm) and double-eyelid fold-palpebral margin distance (medial limbus) (FLmD) in Chinese females and -0.38 and -0.52 mm (P<0.001) for palpebral fissure width (PFW) and lower palpebral margin length (LPML) in Caucasian females. Caucasian males displayed significantly larger palpebral fissure height (PFH), iris diameter (ID), LPML, lateral canthal angle (LCA), canthal tilt (CT), palpebral fissure index (PFI), and canthal angular index (CAI), as well as smaller inner intercanthal distance (EnD), outer intercanthal distance (ExD), and canthal index (CI) than Chinese males (P<0.05). In contrast, Caucasian females showed significantly larger PFW, ID, LPML, LCA, CT, and CAI, as well as smaller EnD, ExD, CI, and medial canthal angle (MCA) than Chinese females (P<0.05). Furthermore, Caucasians showed more prominent double-eyelid folds, except at the pupil center in females. In eyebrow measurements, Caucasian males exhibited non-significant differences with Chinese males, while Caucasian females had significantly larger measurements at lateral positions but smaller ones at the endocanthion than Chinese females (P<0.05). Conclusions:This study established sex- and ethnicity-specific 3D anthropometric data for the periocular region of young Caucasian and Chinese adults. These findings must be considered for periocular disease diagnosis, surgical planning, and outcome evaluation across diverse sexual and ethnic populations.

Background and Objective: Basal cell carcinoma (BCC) is the most common type of malignant tumor and a subtype of non-melanoma skin cancer (NMSC). It has a slow progression, metastasizes extremely rarely, but sometimes causes severe local tissue destruction. The constantly increasing incidence of BCC results from a complex interaction between environmental, genetic, and other risk factors. Several oncogenes and antioncogenes have been proved to be involved in BCC pathogenesis, including the vital effector portions of the hedgehog (HH) signaling pathway (i.e., PTCH1, PTCH2, SMO or SUFU genes), MC1R, and TP53. HH signaling pathway dysregulation is related to dysplasia and carcinoma, including Gorlin syndrome (GS) and sporadic cancers. Mutations caused by ultraviolet (UV) light and/or copy-loss heterozygosity of related genes lead to the abnormal signaling pathway activation, responsible for over 90% of the BCC cases. This review intends to provide a revision of the genetic factors affecting BCC. Methods: The PubMed database was searched with a search algorithm [(basal cell carcinoma) OR (BCC)] AND [(gene) OR (pathway)], till May 2021, to filter out relevant publications. Relevant researches omitted from this search algorithm were also selected from the specific full-text papers reference lists. No language restrictions included in our search. Key Content and Findings: This review provides a revision of several potential mechanisms that may involve in BCC carcinogenesis. Some genetic agents have been considered the risk factors for BCC, including the vital effector portions of the HH signaling pathway, MC1R, and TP53. Certain inherited disorders, including Gorlin syndrome, xeroderma pigmentosum, and Bazex-Dupr & eacute;-Christol syndrome, are considered genetic risk factors for BCC, predisposing BCC at an early age. Other genes, such as BRCA1, BRCA2, CTLA-4, AS3MT, N-Myc and Hippo-YAP pathway target genes (MYCN PTPN14, PPP6C, STK19, LATS1) also show the potential relevance in BCC tumorigenesis and progression. Conclusions: The hereditary basis of BCCs can vary from targeted mutations in the HH signaling pathway to deficiencies of tumor suppressors and melanin synthesis. These may lead to DNA damage and promotes BCC growth. The knowledge and characterization of the BCC genetic factors could underlie the development of new therapies.

Introduction In this study, we measured the volume of customized tumor models in the periocular area using three-dimensional (3D) stereophotogrammetry and evaluated the reproducibility of these measurements. Methods Five tumor models of different colors and sizes were placed in different periocular positions, and 3D facial images were obtained from 68 healthy adult volunteers. Subsequently, the volumes of the tumor models were measured, and the intra- and interrater reproducibility was assessed. Results The gray 6 mm model revealed the highest reliable measurements in both Caucasians (intra- and interrater intraclass correlation coefficients of 0.981 and 0.899, mean absolute difference of 1.446 and 3.327 mm 3 , relative error measurement of 3.497% and 8.120%, technical error of measurement of 1.450 and 3.105 mm 3 , and relative technical error of measurement of 3.506% and 7.580%) and Asians (0.968 and 0.844, 1.974 and 4.067 mm 3 , 4.772% and 9.526%, 2.100 and 4.302 mm 3 , and 5.076% and 10.076%, respectively). The highest reliability of measurements in the lateral upper eyelid (0.88 and 0.95, 4.042 and 3.626 mm 3 , 9.730% and 9.020%, 5.714 and 3.358 mm 3 , and 9.730% and 8.350%, respectively) and medial upper eyelid (0.81 and 0.89, 4.313 and 4.226 mm 3 , 9.730% and 9.020%, 6.098 and 4.069 mm 3 , and 9.730% and 8.350%, respectively) with eyes closed was evident in Caucasians, while the same trend (0.841 and 0.815, 2.828 and 3.757 mm 3 , 9.860% and 9.840%, 4.052 and 4.308 mm 3 , and 9.860% and 9.740%, respectively) was observed in Asians in the medial canthus with eyes closed. Conclusions This study confirms, for the first time, the high reliability of periocular tumor volume measurements using 3D stereophotogrammetry, suggesting its feasibility for eyelid tumor measurement. Further trials are required to investigate its clinical use for documentation and follow-up of different eyelid tumors.

Graves ophthalmopathy (GO), which occurs in autoimmune thyroid disease, can reduce patients' quality of life due to its impact on visual function, physical appearance, and emotional health. Corticosteroids have been the first-line treatment for GO. More recently, the pathogenesis of GO has made significant progress. Various targeting biological agents and immunosuppressive agents make GO management more promising. Fully understanding GO pathogenesis and precise clinical management are beneficial for the prognosis of patients. Therefore, we conducted a comprehensive review of the medical management of GO and summarized research developments to highlight future research issues.

Purpose Portable three-dimensional imaging systems are becoming increasingly common for facial measurement analysis. However, the reliability of portable devices may be affected by the necessity to take three pictures at three time points. The purpose of this study was to evaluate the effectiveness of portable devices for assessing the periocular region. Methods In 60 Caucasian volunteers (120 eyes), four facial scans (twice for each instrument) using the portable VECTRA H2 and static VECTRA M3 devices were performed; patients' heads were kept straight, looking ahead, with a neutral facial expression. One assessor set 52 periocular landmarks in the periocular area of each image and subsequently assessed intra- and inter-device reliability by comparing two within-device measurements and one between-device measurement, respectively. Results The mean absolute difference (MAD) (0.13 and 0.12 units), relative error of measurement (REM) (0.61 and 0.68%), technical error of measurement (TEM)(1.02 and 0.80 units), relative TEM (rTEM) (5.51 and 4.43%), and intraclass correlation coefficient (ICC) (0.89, 0.89) showed good intra-device reliability for M3 and H2; MAD (0.63, 0.62 units), REM (2.83, 2.69%), TEM (1.31, 1.10 units), rTEM (7.62, 5.57%), and ICC (0.79, 0.83) indicated that inter-device reliability deteriorated compared to intra-device reliability and that the inter-device reliability of the first scan (moderate) was lower than that of the average of the two scans (good). Conclusions The portable VECTRA H2 device proved reliable in assessing most periocular linear distances, curve distances, and angles; some improvement in inter-device reliability can be achieved by using the average of two scans.

Purpose To determine age-and sex-related changes in periocular morphology in Caucasians using a standardized protocol. Methods Healthy Caucasian volunteers aged 18–35 and 60–90 years old were recruited from the Department of Ophthalmology, Faculty of Medicine and University Hospital, Cologne, between October 2018 and May 2020. Volunteers with facial asymmetry, facial deformities, history of facial trauma, facial surgery, botox injection, eyelid ptosis, strabismus, or nystagmus, were excluded. Standardized three-dimensional facial photos of 68 young volunteers and 73 old volunteers were taken in this clinical practice. Position changes of endocanthion, pupil center, and exocanthion were analyzed in different age and gender groups, including palpebral fissure width (PFW): distance between endocanthions (En-En), pupil centers (Pu–Pu), exocanthions (Ex-Ex), endocanthion and nasion (En-Na), pupil center and nasion (Pu-Na), exocanthion and nasion (Ex-Na), endocanthion and pupil center (Pu-En), exocanthion and pupil center (Pu-Ex), and palpebral fissure inclination (PFI); angle of endocanthions to nasion (En-Na-En), pupils to nasion (Pu-Na-Pu), exocanthions to nasion (Ex-Na-Ex); endocanthion inclination (EnI), and exocanthion inclination (ExI). Results PFW, En-En, Ex-Na, Pu-Ex, PFI, ExI, and Ex-Na-Ex were significantly different between the young and old groups ( p ≤ 0.004). There were sex-related differences in PFW, Ex-Ex, En-Na, Pu-Na, Ex-Na, Pu-En, PFI, and EnI between both groups ( p ≤ 0.041). Conclusion The position change of the pupil is minimal relative to age; it is preferred to establish the reference plane to describe periocular changes. The endocanthion tends to move temporally and inferiorly, while the exocanthion tends to shift nasally and inferiorly with age.

Background To explore the research trends for uveal melanoma with bibliometric methods using Web of Science Core Collection (WoSCC) and PubMed (PM). Methods To find UM-related studies, "uveal melanoma" was used as search term in the WoSCC and PM for the period time from 2000 to 2020. Bibliographic coupling analysis was used to investigate the journals with the highest number of UM-related publications. VOSviewer (VV) was used for mapping the knowledge domain and visualizing the co-occurrence of terms, authors, organizations, countries, co-citation literature, and keywords. The knowledge map based on WoSCC and PM was compared. Results In the WoSCC 3,748 articles were found, while in PM the search resulted in 3,403 articles. The number of original articles has steadily grown in general in the past two decades. The top ten authors were contributing to 23% (n = 856) of all publications, while the top 10 institutions published 41% (n = 1524) of all articles. The top 3 journals with the highest number of publications for UM-related research included Investigative ophthalmology & visual science, Ophthalmology, and British Journal of Ophthalmology. Co-occurrence analysis based on author keywords showed 6 clusters. The most frequent keywords included are metastasis, prognosis, and brachytherapy. The latest research hotspots focused on BAP1, immunotherapy and GNAQ. Conclusions Genetics and immunology are the latest research frontiers in uveal melanoma. There is a clear need for interdisciplinary, molecular and clinical research approaches to improve the fatal prognosis of uveal melanoma patients.