Personalized treatment approaches in intraocular cancer.

Background: Intraocular malignant tumors represent a severe disease that threatens vision as well as life. To better extend the life of the patient, preserve visual function, and maintain ocular aesthetics, selecting the appropriate timing and methods of treatment becomes crucial. Main text: With the continuous advancement of medical technology, the techniques and methods for treating intraocular malignant tumors are constantly evolving. While surgery was once considered the optimal method to prolong patient survival and prevent local recurrence, the discovery and application of various treatments such as radiotherapy, laser therapy, chemotherapy, cryotherapy, and monoclonal antibodies have led to a greater diversity of treatment options. This diversity offers more possibilities to develop personalized treatment plans, and thereby maximize patient benefit. This article reviews the various treatment methods for intraocular malignant tumors, including indications for treatment, outcomes, and potential complications. Conclusions: Differentiating small intraocular malignant tumors from pigmented lesions is challenging, and ongoing monitoring with regular follow-up is required. Small to medium-sized tumors can be treated with radiotherapy combined with transpupillary thermotherapy. Depending on the tumor's distance from the optic disc, surgery with partial resection may be considered for distant tumors, while proximal tumors may require complete enucleation. Systemic chemotherapy has been widely applied to patients with retinal tumors, lymphomas, and intraocular metastatic cancers, but has limited efficacy in patients with choroidal melanoma. Antagonists of Vascular Endothelial Growth Factor (Anti-VEGF) drugs can improve patient vision and quality of life, while the efficacy of immunotherapy and molecular targeted therapy is still under research.

FACE-Q eye module for measuring patient-reported outcomes in blepharoplasty surgery: A validation study.

This study aimed to conduct a linguistic validation of all FACE-Q eye module scales in German, and to evaluate the reliability and validity of the scales in patients with blepharoplasty. According to international recommendations, all FACE-Q scales and checklists were translated from English to German. Psychometric testing of blepharoplasty surgery-related scales of translated versions were administered to patients with blepharochalasis or dermatochalasis and a history of blepharoplasty surgery (n = 64; 11 scales) or no history of blepharoplasty surgery (n = 65; seven scales), and to a group of control subjects (n = 64; seven scales). Most of the subscales showed acceptable internal consistency, with Cronbach's alphas ranging from 0.75 to 0.97. Intraclass correlation coefficients were high (0.70-0.92), indicating good reliability, with total values of 0.63 (95% CI 0.46-0.76) and 0.68 (95% CI 0.53-0.80) for the upper eyelid and social function scores, respectively. There was good discriminability between pre- and post-blepharoplasty patients and normal subjects (p < 0.05). The German-language version of the FACE-Q eye module is a successfully validated and helpful tool for assessing outcomes after blepharoplasty surgery, especially with respect to 'satisfaction with overall facial appearance', 'psychological well-being, social function', 'decision satisfaction, outcome satisfaction', and 'early-life impact recovery'.

Dynamic Measurement and Analysis of Upper Eyelid Changes Using Ultrasound Biomicroscopy.

PURPOSE: To define the regular upper eyelid anatomy and their changes during dynamic motion using ultrasonographically depicted structures. DESIGN: A cross-sectional study. METHODS: High-resolution ultrasound biomicroscopy (50MHz) was performed on 84 upper eyelids of 42 healthy volunteers without evidence of eyelid conditions. The skin-orbicularis oculi complex (SOOC), levator aponeurosis, and Müller's muscle-conjunctival complex were imaged. The thickness of these structures was measured in primary gaze and downgaze positions. RESULTS: SOOC and levator aponeurosis thickness was bigger with eyes open than with eyes closed (p < 0.01). With eyes closed, the thickness of SOOC on the pupillary midline and levator aponeurosis was positively correlated with age (p < 0.05, p < 0.01, respectively), and the thickness of levator aponeurosis and SOOC on the pupil midline was also positively correlated with BMI index (p < 0.05). Similarly, SOOC thickness on the medial and lateral canthus line is also positively correlated with BMI index and age (p < 0.05, p < 0.01, respectively). As for the differences between genders, the mean thickness of SOOC and levator aponeurosis was statistically different (p < 0.05, respectively). The magnitude of levator aponeurosis thickness in men varied more than in women in different ocular positions (p < 0.05). All measurements had an intramethod between 0.624 and 0.792, and inter-rater ICC and intrarater ICC between 0.748 and 0.850. CONCLUSIONS: Ultrasound biomicroscopy represents a noninvasive tool for the visualization of upper eyelid morphology. Expanding its application can help to understand the dynamics of upper eyelid physiological movement, aging, and disease research in different populations and evaluate surgical outcomes.

[Metastasis in the periocular region]. / Metastase in der periokulären Region.

Orbital and periocular metastatic tumors used to be considered very rare; however, with the constant updating of drugs and detection methods for cancer treatment, new chemotherapies and radiation treatments are being used. The life expectancy of cancer patients has become longer and periocular metastases are becoming easier to detect. Our knowledge of this rare disease of metastases also needs to be updated. This article reviews the incidence, symptomatic presentation, clinical features, diagnostic approaches and current treatment of metastatic tumors of the orbit and ocular adnexa in these patients.

A UV-related risk analysis in ophthalmic malignancies: Increased UV exposure may cause ocular malignancies.

Purpose: To explore the role of ultraviolet radiation (UVR) in the occurrence and development of various ocular malignancies. Methods: In this article, we retrieved ocular malignancy data from the Global Cancer Observatory (GCO) and performed correlation analysis with the global UV index and sunshine duration. We searched for associated studies using the following databases: Embase, Pubmed, Cochrane Library, and Google Scholar. We conducted the literature by searching the Mesh terms denoting an exposure of interest ("UV radiation", "ultraviolet rays", and "ocular malignancies", All studies included are published until December 30, 2023 without language restrictions. Results: The mechanisms and epidemiological statistics of UVR on the onset and progression of eyelid malignancies are the most studied and clear. The role of UVR in conjunctival melanoma is similar to that in eyelid melanoma. The relationship between uveal melanoma and UVR is controversial, however, it may have at least a certain impact on its prognosis. UVR causes ocular surface squamous neoplasia by further activating HPV infection. Conclusions: UVR is a decisive risk factor for ocular malignancies, but the incidence of ultraviolet-induced tumors is also affected by many other factors. A correct and comprehensive understanding of the mechanisms of UVR in the pathogenesis of ocular malignant tumors can provide patients with more effective and selective immune regulation strategies.

Periocular Asymmetry Index in Caucasian Populations Using Three-dimensional Photogrammetry Assessment.

OBJECTIVE: To quantitatively assess the periocular asymmetry and investigate its sex and age-related differences in a Caucasian population using three-dimensional (3D) stereophotogrammetry. METHOD: Standardized 3D photos of the periocular region of 301 Caucasians were taken using the VECTRA M3 3D Imaging System. Standardized landmarks were positioned, and data measurements in the periocular region were obtained from these images using VAM software and assessed using intraclass correlation coefficients (ICC) for reliability. Absolute differences and asymmetry index between the right and the left periocular region were calculated with a focus on gender and age-related differences. RESULT: Fissure height asymmetry was positively correlated with age (p < 0.01). Furthermore, reflex distance asymmetry was positively correlated with age in the elderly group (p < 0.05). Absolute differences of upper eyelid crease were 0.65 ± 0.79 mm for females and 0.90 ± 0.94 mm for males (p < 0.05). In the elderly group, the absolute differences of reflex distance were 0.664 ± 0.471 mm for males and 0.470 ± 0.408 mm for females (p < 0.05), while the absolute differences of fissure height were 0.619 ± 0.469 mm and 0.436 ± 0.372 mm, respectively (p < 0.05). All measurements had an inter-rater ICC and intra-rater ICC between 0.761 and 0.957. CONCLUSION: Periocular asymmetry is more prominent in older and male people. 3D photogrammetry is a reliable tool to detect periocular asymmetry and might provide an accurate and effective reference for periocular cosmetic, plastic, and reconstructive surgery in the clinical routine. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors. www.springer.com/00266 .

Personalized treatment concepts in extraocular cancer.

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.

The structure and function of the human choroid.

In this manuscript, the structure of the human choroid is reviewed with emphasis of the macro- and microscopic anatomy including Bruch's membrane, choriocapillaris, Sattler's and Haller's layer, and the suprachoroid. We here discuss the development of the choroid, as well as the question of choroidal lymphatics, and further the neuronal control of this tissue, as well as the pathologic angiogenesis. Wherever possible, functional aspects of the various structures are included and reviewed.

Quantifying Dermatochalasis Using 3-Dimensional Photogrammetry.

BACKGROUND: Creating an appropriate treatment plan for patients with dermatochalasis requires careful investigation of the periocular region. Utilizing photographic documentation can assist physicians in conducting preoperative analysis and managing expectations regarding surgical outcomes. OBJECTIVES: This study aimed to quantify the periocular characteristics of dermatochalasis patients using standardized 3D imaging and to compare age and sex-related changes in periocular features. METHODS: In this cross-sectional study, we recruited 145 Caucasian patients with periocular dermatochalasis, comprising 48 men and 97 women, aged between 35 and 91 years. Standardized three-dimensional facial photographs were taken using the 3D Imaging system VECTRA M3. Linear dimensions, curve length, angle, indices, and sizes were measured and analyzed, including palpebral fissure height (PFH), palpebral fissure width (PFW), upper lid fold-palpebral margin distance (FPD), upper palpebral margin length (UPML), lower palpebral margin length (LPML), canthal tilt (CT), palpebral fissure index (PFI), upper eyelid area, and ocular surface area. RESULTS: In the female group, the left-side PFH was slightly larger than the right-side PFH (P = 0.023), but the difference was less than 1mm. The corresponding PFI also showed a difference in the female group (P = 0.009). Statistically significant differences were shown in genders for specific parameters, except PFI (P = 0.251) and CT (P = 0.098). Among males, PFW (R = -0.523, p < 0.001) and LPML (R = -0.514, P = 0.264) decreased moderately with age. The correlation between UPML and age was weak (R = -0.367, P = 0.010). Similarly, among females, moderate correlations were found between age and PFW (R = -0.566, P < 0.001) and LPML (R = -0.537, P < 0.001). Additionally, PFH (R = -0.315, P = 0.002), UPML (R = -0.381, P < 0.001), and ocular surface area (R = -0.457, P < 0.001) showed weak correlations with age. CONCLUSIONS: The study found that dermatochalasis usually affects both eyes simultaneously, and age is a significant factor in the morphological changes of certain periocular features regardless of sex. The PFI is not influenced by age or sex. These findings may provide useful information for surgical planning and understanding age-related changes in the periocular area. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Differential diagnostics of chronic eye pain from a neurological perspective-What can also lie behind it]. / Differenzialdiagnosen chronischer Augenschmerzen aus neurologischer Sicht ­ Was auch dahinterstecken kann.

Periorbital pain and pain in the eye may arise from nociceptive processes such as chronic ocular surface destruction and inflammation, from neuropathic processes or often from a combination of different mechanisms. An important differential diagnosis are primary headache disorders and other neurological diseases, for example of inflammatory origin, which trigger secondary pain. Chronic eye pain therefore requires interdisciplinary collaboration in the diagnostics and treatment.

Evaluation of the Portable Next-Generation VECTRA H2 3D Imaging System for Measuring Upper Eyelid Area and Volume.

BACKGROUND: Although a portable 3-dimensional (3D) imaging system has been used for periocular measurement analysis, this system has yet to be tested and validated for periocular area and volume measurements. OBJECTIVES: The aim of this study was to define the upper eyelid and upper eyelid fold region through a modified landmark strategy and validate a portable 3D imaging system for area and volume measurements in this periocular region. METHODS: Eighty-one healthy adult Caucasians underwent 3D facial imaging with the VECTRA M3 (static) and VECTRA H2 (portable) 3D imaging systems (Canfield Scientific, Inc., Parsippany, NJ). Subsequently, the upper eyelid and upper eyelid fold regions were selected according to a modified landmark localization strategy. Direct measurements of area and volume were performed to assess intrarater, interrater, intramethod, and intermethod reliability, and to compare the agreement between the 2 devices. RESULTS: The VECTRA M3 and H2 showed high reliability on upper eyelid area measurements. Excellent intra-, inter-, and intramethod reliability agreements were observed in intraclass correlation coefficient; very good agreement in intrarater reliability was observed in the relative error of measurement (REM) and relative technical error of measurement (rTEM); and good inter- and intramethod reliability were observed in the REM and rTEM. For area measurement of the upper eyelid fold, the intrarater, interrater, and intramethod reliability of the M3 was lower than that of the H2. Both systems had poor intrarater, interrater, and intramethod reliability for volume measurements in the upper eyelid and upper eyelid fold region. CONCLUSIONS: This new portable 3D imaging system achieved excellent or very good reliability values for standardized direct measurements of the upper eyelid and upper eyelid fold region, although volume measurements seem less reliable.

Roles of Optineurin and Extracellular Vesicles in Glaucomatous Retinal Cell Loss.

OBJECTIVE: To explore the role of extracellular vesicles (EVs) in the pathogenesis of glaucoma caused by E50K mutation. METHODS: A photoreceptor cell line, RGC-5, was transfected with empty plasmids and plasmids expressing wild-type (WT) optineurin (OPTN) or E50K OPTN to investigate the effects of OPTN glaucoma as well as to identify the role of EVs in glaucoma pathology. The RGC-5 cells were also stimulated with glutamate, and their viability was evaluated using flow cytometry or CCK-8 assay. EVs were extracted, labeled with PKH-26, and added into the medium for normal RGC-5 culture, and the status of the cells was observed thereafter. RESULTS: WT OPTN overexpression, E50K OPTN, and glutamate stimulation induced apoptosis of RGC-5 cells. However, when glutamate stimulation was used as an add-on treatment, the degree of apoptosis in WT OPTN-overexpressing RGC-5 cells was significantly lower than that in E50K OPTN-expressing and normal RGC-5 cells. The viability of normal RGC-5 cells was reduced when co-cultured with WT OPTN-overexpressing RGC-5 or E50K OPTN-overexpressing RGC-5. EVs released by the latter two transfected lines similarly reduced normal RGC-5 survival. CONCLUSION: Our results indicate that WT OPTN overexpression may lead to photoreceptor apoptosis. However, overexpression also confers a degree of protection against high concentrations of extracellular glutamate. Additionally, EVs released by transfected RGC-5 cells may regulate the cell state. These findings may improve our understanding of the mechanisms of cell-cell interactions in pathological conditions, providing a basis for the use of EVs as novel targets for early diagnosis and treatment of glaucoma.

A novel standardized approach for the 3D evaluation of upper eyelid area and volume.

Background: Three-dimensional (3D) surface imaging and morphometrics are becoming the preferred craniofacial surface imaging modality. However, as a unique advantage of 3D imaging, areal and volumetric measurements have been rarely conducted and validated for evaluating soft tissue change in the periocular region, especially the upper eyelids. Therefore, based on an existing periocular landmark identification strategy, we proposed a novel modified method to define a standardized upper eyelid region for areal and volumetric measurements and validate its reliability for future clinical application. Methods: Forty-four healthy adult volunteers were enrolled in this cross-sectional study. Three-dimensional facial images were taken with a 3D imaging system. Subsequently, the upper eyelid region selection and areal and volumetric measurements were conducted using a modified landmarks localization strategy to evaluate their intrarater, interrater, and intramethod reliability. Results: Areal measurement of the upper eyelid revealed highly reliable outcomes for intraclass correlation coefficient (ICC), mean absolute difference (MAD), relative error measurement (REM), technical error of measurement (TEM), and relative technical error of measurement (%TEM) of 0.982, 0.1620 cm2, 2.9%, 0.1510 cm2, and 2.7% for intrarater reliability, respectively; 0.969, 0.2076 cm2, 3.7%, 0.1930 cm2, and 3.5% for interrater reliability, respectively; and 0.917, 0.3636 cm2, 6.5%, 0.3354 cm2, and 6.0% for intramethod reliability, respectively. Unsatisfactory results were found for the volumetric measurement of the upper eyelid: the ICC, MAD, REM, TEM, and %TEM estimates for intrarater reliability were 0.992, 0.2299 mL, 10.3%, 0.2414 mL, and 10.8%, respectively; for interrater reliability, these values were 0.985, 0.2749 mL, 12.3%, 0.3253 mL, and 14.6%, respectively; and for intramethod reliability, these values were 0.433, 1.6716 mL, 77.9%, 2.0615 mL, and 96.1%, respectively. Conclusions: This is the first study to propose a standardized upper eyelid region selection strategy and simultaneously validate its reliability for 3D areal and volumetric measurements. This study confirmed the high-level reliability of areal measurement and poor reliability of volumetric measurement based on direct measurements using a single image, which may provide better results when this method is combined with the image overlapping and registration procedure. However, this is subject to further validation. Nonetheless, this method could provide quantitative areal and volumetric data on the upper eyelids and might have widespread application potential in the future.

Age-related changes of the periocular morphology: a two- and three-dimensional anthropometry study in Caucasians.

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.

Reproducibility of Three-Dimensional Volumetric Measurement of Periocular Tumor Models.

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 mm3, relative error measurement of 3.497% and 8.120%, technical error of measurement of 1.450 and 3.105 mm3, and relative technical error of measurement of 3.506% and 7.580%) and Asians (0.968 and 0.844, 1.974 and 4.067 mm3, 4.772% and 9.526%, 2.100 and 4.302 mm3, 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 mm3, 9.730% and 9.020%, 5.714 and 3.358 mm3, and 9.730% and 8.350%, respectively) and medial upper eyelid (0.81 and 0.89, 4.313 and 4.226 mm3, 9.730% and 9.020%, 6.098 and 4.069 mm3, 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 mm3, 9.860% and 9.840%, 4.052 and 4.308 mm3, 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.

Recent advances in graves ophthalmopathy medical therapy: a comprehensive literature review.

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.

Therapy Failure and Resistance Mechanism in Eyelid and Ocular Surface Tumors.

Malignant tumors of the eyelids and ocular surface are common ocular malignancies. At present, surgical treatment is mostly the first choice for these types of tumors. However, postoperative tumor recurrence and metastasis are still regarded as failures in the treatment of such malignancies. Based on this, malignant tumors of the eyelid and ocular surface are sometimes accompanied by local adjuvant chemotherapy and systemic chemotherapy to treat patients with relapse, invasion of adjacent tissues, and systemic metastases. Still, drug resistance greatly affects the treatment effect. This review lists several mechanisms of recurrence and metastasis of ocular surface and eyelid tumors after surgery, as well as mechanisms that may lead to non-surgical treatment or drug resistance.