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.

A comparative study of cystoid macula edema following glaucoma drainage device surgery versus trabeculectomy.

PURPOSE: To assess and compare the risk for development of cystoid macula edema (CME) after glaucoma drainage device (GDD) implantation versus conventional trabeculectomy with mitomycin (trab) for glaucoma. METHODS: Retrospective review of consecutive patients receiving trab or GDD implantation between 2016 and 2018. Inclusion criteria were availability of pre- and postoperative spectral domain optical coherence tomography (SD-OCT) of the macula. SD-OCT images were evaluated for presence of CME qualitatively, central subfield thickness (CST) and macular volume (MV). RESULTS: 73 eyes could be included, 42 received trab and 31 GDD surgery. Eyes receiving trab on average had 0.8 ± 0.8 previous intraocular operations, while eyes with GDD implantation had 3.1 ± 1.9 (p < 0.001). Occurrence of postoperative CME was significantly more frequent after GDD implantation (6 out of 31 (19.4%)) than after trab (2 out of 42 eyes = 4.8%), (p = 0.049). Mean preoperative CST as well as MV was comparable in both groups (CST before trab: 282.7 ± 23.0 µm, CST before GDD 284.2 ± 27.3 µm, p = 0.287; MV before trab: 7.8 ± 1.1 mm3, MV before GDD: 8.0 ± 0.8mm3, p = 0.305). Mean postoperative CST and MV were significantly higher after GDD (CST 338.5 ± 129.3 µm, MV 8.8 ± 2.6 mm3) than after trabeculectomy (CST 290.6 ± 60.2 µm, p = 0.038; MV 7.8 ± 1.2mm3, p = 0.039). CONCLUSIONS: In real-life conditions, GDD surgery seems to be associated with a higher risk to develop CME when compared to conventional trabeculectomy. This information may be helpful for glaucoma surgeons to advise the patients on postoperative risks of surgery.

Laryngeal Mask Airway Versus Endotracheal Intubation during Lacrimal Duct Stenosis Surgery in Children-A Retrospective Analysis.

Background: The use of laryngeal masks in the surgical treatment of infantile lacrimal duct stenosis is controversial due to the potential risk of aspiration. Aims: This study investigates airway procedures in children aged <6 years for surgery of lacrimal duct stenosis in a tertiary care university hospital. Methods: After institutional approval, airway procedures, duration of anesthesiological measures, and airway-related complications were retrospectively analyzed. Patients were divided into two groups according to the airway procedures used (endotracheal tube [ET] vs. laryngeal mask [LMA] airway). Associations were calculated using the Chi-square test or Mann-Whitney U-test. Results: Clinical data of 84 patients (ET n = 36 [42.9%] vs. LMA n = 48 [57.1%]) were analyzed. There were no significant differences in surgical treatment, age distribution, and pre-existing conditions between the groups. None of the patients showed evidence of tracheal aspiration or changes in measured oxygen saturation. LMA airway shortened time for anesthesia induction (p = 0.006) and time for recovery/emergence period (p = 0.03). In contrast, the time to discharge from the recovery room was significantly prolonged using LMA (p = 0.001). A total of 7 adverse events were recorded. Five of these were directly or indirectly related to ET (laryngo-/bronchospasm; muscle relaxant residual). Conclusions: LMA airway for infantile lacrimal duct stenosis seems to be a safe procedure and should be used in appropriate pediatric patients due to its lower invasiveness, low complication rate, and time savings.

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.

Eight weeks of exercise intervention improves visuomotor and functional capacity, performance, and physiological profile in a patient with choroidal melanoma.

The aim of this case study was to investigate the effects of an 8-wk combined exercise intervention, consisting of visual-coordinative and high-intensity interval training (HIIT), on the physical and visuomotor-functional capacity, performance, and physiological profile of a moderately active 29-yr-old man diagnosed with choroidal melanoma of the left eye. Data were collected on three occasions: at the initial diagnosis (T0), after hospitalization and radiotherapy treatment (T1), and following the recovery through the exercise intervention (T2), spanning a total of 17 wk. The primary outcome variables consisted of visuomotor and functional tests (VFTs), cardiorespiratory fitness (CRF), and microvascular circulation measured via flicker light-induced dilation (FiD). For visuomotor tests in general, a significant decline was observed between baseline T0 and T1 (by 6%-22%), followed by significant improvements at T2 (by 11%-36%), surpassing the initially observed T0 values. The cardiopulmonary exercise testing (CPET)-derived parameters exhibited a similar pattern, declining from T0 to T1 [by 8%-12% for peak V̇o2, peak power output (PO), and CPET duration, respectively], with a subsequent recovery observed in response to 8 wk of exercise training (T2), resulting in increases of 11%-25% for V̇o2, peak PO, and CPET duration. Interestingly, the dilation of both arteries and veins in response to the FiD stimulus exhibited a twofold increase compared with baseline levels. Our results suggest that the 8-wk exercise intervention improved patients' VFT and CRF profiles and exceeded baseline values. Additional investigation, particularly through randomized controlled trials, is needed to comprehensively explain changes in FiD.NEW & NOTEWORTHY Results presented here suggest that combined visual-coordinative and HIIT training improves the visual-functional capacity, performance, and physiological profile of choroidal melanoma patients during treatment recovery. This case study lays the groundwork for further research concerning exercise therapy in this unique patient population. In addition, further investigation is required to fully comprehend the combined effects of exercise and radiation therapy on vasculature and oxygenation in patients with choroidal melanoma.

Combined Osteopontin Blockade and Type 2 Classical Dendritic Cell Vaccination as Effective Synergetic Therapy for Conjunctival Melanoma.

Angiogenesis and immune protection are essential at the onset of tumorigenesis. Angiogenesis serves to nourish the tumor, and prevention of immune defenses, for example, by dendritic cells (DCs), allows tumor growth. In this study, we investigated whether there are factors with dual functions that are both angiogenic and immunomodulatory and represent a therapeutic target. We analyzed 1) innate immune responses intratumorally and in draining lymph nodes and 2) angiogenic factors in conjunctival melanoma (CM), a potentially lethal malignant tumor at the ocular surface whose immune and vascular responses are largely unknown. For this purpose, an HGF-Cdk4R24C model in immunocompetent C57BL/6 mice was used and revealed that CD103- type 2 classical DC (cDC2s) were the most abundant DC subtype in healthy conjunctiva, whereas in CM, CD103- cDC2s, CD103+ type 1 cDCs, monocyte-derived DCs, and plasmacytoid DCs were significantly increased. In our analysis of angiogenic factors in CM, the examination of 53 angiogenesis-related factors that might interact with DCs identified osteopontin (OPN) as a major tumor-derived protein that interacts with DCs. Consistent with these findings, 3) a dual therapeutic strategy that inhibited tumor cell function by an OPN blocking Ab while enhancing the immune response by cDC2 vaccination resulted in 35% failure of tumor development. Moreover, tumor progression, monocyte-derived DC infiltration, and intratumoral angiogenesis were significantly reduced, whereas survival and CD8+ T cell infiltration were increased in treated mice compared with the control group. Therefore, we identified OPN blockade in combination with cDC2 vaccination as a potential future therapeutic intervention for early stages of CM by combining antiangiogenic and host immune stimulating effects.

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.

[Chronic eye pain]. / Der chronische Augenschmerz.

Numerous conditions in the field of ophthalmology are associated with pain in or around the eye. Chronic pain associated with the eye is a common finding in the daily routine of ophthalmologists and can be associated with primary ocular or extraocular diseases as well as with other conditions. Appropriate diagnostic assessment and management of people with chronic pain requires an understanding of the condition based on the biopsychosocial model in which the interactions of biological/somatic, psychological and social factors are determining pain and suffering. Beyond the ophthalmological findings,  close interdisciplinary cooperation and assessment are required. Therefore, if eye pain is insufficiently responsive to treatment or if symptoms of chronic pain are evident, pain medicine expertise should be involved. The management of chronic ocular pain is based on interdisciplinary multimodal approaches, in addition to the ophthalmologist-specific approaches. These focus on self-efficacy, patient competence and acceptance of pain as central goals of treatment rather than pain relief. Patient information, education and the development of a suitable concept by the interdisciplinary team are essential therapeutic aspects in this context.

Immediate postoperative topical lidocaine gel for the treatment of eye pain following corneal abrasion in descemet membrane endothelial keratoplasty (DMEK) under general anaesthesia: a pilot retrospective analysis.

BACKGROUND: Patients undergoing corneal abrasion as part of Descemet membrane endothelial keratoplasty (DMEK) under general anesthesia suffer from early burning pain postoperatively. This pain appears to be poorly treatable with systemic analgesics. This study aims to evaluate postoperative pain management using topical lidocaine gel after DMEK with iatrogenic corneal abrasion. METHODS: Retrospective analysis of 28 consecutive patients undergoing DMEK with corneal abrasion from October 19, 2021, to November 12, 2021, at a German university hospital. Patients during week 1 and 2 received peri-operative standard pain treatment (cohort S) and additional local lidocaine gel during week 3 and 4 immediately postoperatively (cohort L). RESULTS: 13 patients were included in cohort S and 15 patients in cohort L. At awakening all patients (100%) in cohort S reported burning pain, and six of 15 patients (40%) in cohort L reported burning pain. Burning pain scores were significantly lower in cohort L (p < 0.001 at awakening, p < 0.001 at 10 min, p < 0.001 at 20 min, p < 0.001 at 30 min, p = 0.007 at 40 min after awakening, and p < 0.001 at leaving recovery room). No significant differences between cohort S and cohort L were detected concerning surgical outcome during 1-month-follow-up (p = 0.901 for best corrected visual acuity). CONCLUSION: Patients undergoing DMEK with corneal abrasion suffer significant pain in the recovery room. A single dose of topic lidocaine gel reduces the early postoperative burning pain sufficiently and does not affect the surgical outcome.

[Viral Conjunctivitis: Findings, Therapy, and Prophylaxis]. / Virale Bindehautentzündungen: Befunde, Therapie und Prophylaxe.

Viral conjunctivitis is one of the most common acute eye diseases. The fall and winter months are known to be the main season for viral infections which is also reflected in the ophthalmological outpatient clinics. Viral conjunctivitis is often accompanied by symptoms of the upper and lower respiratory tract, fever, chills, arthralgia or skin lesions. The spectrum of pathogens comprises DNA viruses such as Adeno-, Herpes simplex and Molluscum contagiosum as well as RNA viruses. Symptoms caused by pandemic pathogens such as SARS-CoV-2 and mpox viruses can also cause ocular manifestation. Viral conjunctivitis is often self-limiting leaving no residual symptoms, however an ophthalmologist should be consulted if there are inflammatory symptoms of the anterior eye accompanied by visual disturbance. It is particularly important to recognize the affection of corneal or even intraocular structures early to initiate an adequate and effective therapy. Affection of the cornea, vitreus or retina can result in temporary or permanent impairment of the field of vision and visual acuity. The diagnosis is usually made without further tests on the basis of the typical clinical presentation. Rapid tests or PCR diagnostics are also available for confirmation. In most patients the treatment is symptomatically with artificial tears and antibiotic eye drops in cases accompanied by secondary bacterial infections, not prophylactically. If the cornea or other ocular structures are affected by certain viruses, local as well as systemic virostatic therapy is initiated. The most important prophylactic measure is meticulous and consistent hygiene.

P35-A133†Novel eccentric corneoscleral donor preparation technique providing corneoscleral tectonic and central split corneal grafts for multiple recipients.

Today, split cornea technique is an established procedure and is mostly used for two recipients by combining deep anterior lamellar keratoplasty (DALK) and Descemet membrane endothelial keratoplasty (DMEK) surgeries. However, for some surgical interventions including block excision with tectonic corneoscleral grafting, split cornea procedure is not planned regularly up to now. In the run-up for this procedure, normally a donor cornea with a bigger scleral ring is gained. Nonetheless, the preparation of the tectonic graft for covering the corneoscleral defect after block excision results in a rest donor cornea transplant which is normally too small for further regular size penetrating keratoplasties (PKs) or combined DALK/DMEK surgeries. However, using a modified donor transplant trephination technique, a corneoscleral transplant for regular size keratoplasties can be gained, also after preparation of a tectonic graft for block excision. Herein, we describe shortly this novel donor preparation technique, the differences compared to the standard procedure, possible applications, and the advantages and disadvantages for the first time.

Noradrenergic neuromodulation in ageing and disease.

The locus coeruleus (LC) is a small brainstem structure located in the lower pons and is the main source of noradrenaline (NA) in the brain. Via its phasic and tonic firing, it modulates cognition and autonomic functions and is involved in the brain's immune response. The extent of degeneration to the LC in healthy ageing remains unclear, however, noradrenergic dysfunction may contribute to the pathogenesis of Alzheimer's (AD) and Parkinson's disease (PD). Despite their differences in progression at later disease stages, the early involvement of the LC may lead to comparable behavioural symptoms such as preclinical sleep problems and neuropsychiatric symptoms as a result of AD and PD pathology. In this review, we draw attention to the mechanisms that underlie LC degeneration in ageing, AD and PD. We aim to motivate future research to investigate how early degeneration of the noradrenergic system may play a pivotal role in the pathogenesis of AD and PD which may also be relevant to other neurodegenerative diseases.

[Congenital anomalies in lacrimal drainage]. / Angeborene Fehlbildungen der ableitenden Tränenwege.

Congenital dacryostenosis is the most common reason for ophthalmic consultation in childhood. It is most often caused by persisting of Hasner's membrane. However, congenital malformations of the lacrimal drainage system can also occur in rare cases. In the area of the proximal lacrimal drainage system, supernumerary lacrimal puncta and canaliculi can arise as well as diverticula, fistula, and atresia. The distal lacrimal drainage system can be affected by fistulas, amniotoceles, and cysts. Association of lacrimal malformations with congenital systemic diseases is reported in about 10% of cases. Depending on the severity of the symptoms, surgical rehabilitation can be performed, and endoscopic procedures and modern lacrimal drainage intubation systems may be employed.

[Pain therapy in children following ophthalmic surgery]. / Schmerztherapie bei Kindern nach ophthalmochirurgischen Eingriffen.

Pain following eye surgery is often described as being relatively moderate; however, there are also procedures that lead to a pronounced pain experience. Particularly in pediatric patients, pain therapy is often insufficient due to a lack of knowledge and fear of complications. These individual and organizational deficits lead to unnecessary discomfort for children and parents. Each institution providing surgical treatment must have pain management concepts in its portfolio for the appropriate age groups. This includes a child-oriented setting, age-appropriate information, systematic pain assessment, and pain protocols. Pain management should be planned prior to surgery and individually adapted as it progresses. Children have a right to a perioperative course with low stress and pain.

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.