Multiple use of preservative-free single dose unit dexamethasone 0.1% eye drops is safe within 24 hours.

BACKGROUND: Unpreserved single-dose unit (SDU) eye drops are commonly used to avoid benzalkonium chloride-related toxicity. Although intended for single use, many patients report off-label repeated use of SDUs over a prolonged period. We investigated whether repeated use of dexamethasone 0.1% SDUs in the same patient increases the bacterial contamination rate. METHODS: We prospectively enrolled patients scheduled for inpatient corneal and glaucoma surgery receiving dexamethasone 0.1% SDU four times per day from the same vial. To assess contamination rates, one drop from the vial was cultured immediately after opening the SDU (t0), 10 hours later after four drop applications (t10) and 24 hours after opening without further drop applications (t24). Conjunctival swabs were taken before and after drop application. Contamination rate was assessed with a standard clinical culturing protocol without introducing a positive control. RESULTS: 110 eyes of 109 patients were evaluated. Drops collected immediately after opening the SDU (t0) were contaminated in 9/110 cultures (8.1%). At t10, 13/110 cultures were contaminated (11.8%; p=0.267) and 11/110 at t24 (10.0%; t24 vs t0; p=1.00). In 5 of 21 cases of contaminated drops at t10 and/or t24, the same isolates were cultured from the initial conjunctival swab and the SDU. In three cases, the same bacterial species was found in consecutive samples. CONCLUSION: The contamination rate of the SDU did not increase after multiple use within 24 hours. Contamination from fingertip flora was more likely than from ocular surface flora. Reuse of dexamethasone 0.1% SDU in the same patient within 24 hours appears to be safe.

Neuroinflammation and Dyskinesia: A Possible Causative Relationship?

Levodopa (L-DOPA) treatment represents the gold standard therapy for Parkinson's disease (PD) patients. L-DOPA therapy shows many side effects, among them, L-DOPA-induced dyskinesias (LIDs) remain the most problematic. Several are the mechanisms underlying these processes: abnormal corticostriatal neurotransmission, pre- and post-synaptic neuronal events, changes in gene expression, and altered plasticity. In recent years, researchers have also suggested non-neuronal mechanisms as a possible cause for LIDs. We reviewed recent clinical and pre-clinical studies on neuroinflammation contribution to LIDs. Microglia and astrocytes seem to play a strategic role in LIDs phenomenon. In particular, their inflammatory response affects neuron-glia communication, synaptic activity and neuroplasticity, contributing to LIDs development. Finally, we describe possible new therapeutic interventions for dyskinesia prevention targeting glia cells.

Unveiling molecular insights: in silico exploration of TLR4 antagonist for management of dry eye syndrome.

BACKGROUND: Dry eye disease is the most commonplace multifractional ocular complication, which has already affected millions of people in the world. It is identified by the excessive buildup of reactive oxygen species, leading to substantial corneal epithelial cell demise and ocular surface inflammation attributed to TLR4. In this study, we aimed to identify potential compounds to treat of dry eye syndrome by exploring in silico methods. METHODS: In this research, molecular docking and dynamics simulation tests were used to examine the effects of selected compounds on TLR4 receptor. Compounds were extracted from different databases and were prepared and docked against TLR4 receptor via Autodock Vina. Celastrol, lumacaftor and nilotinib were selected for further molecular dynamics studies for a deeper understanding of molecular systems consisting of protein and ligands by using the Desmond module of the Schrodinger Suite. RESULTS: The docking results revealed that the compounds are having binding affinity in the range of -5.1 to -8.78 based on the binding affinity and three-dimensional interactions celastrol, lumacaftor and nilotinib were further studied for their activity by molecular dynamics. Among the three compounds, celastrol was the most stable based on molecular dynamics trajectory analysis from 100 ns in the catalytic pockets of 2Z63.pdb.pdb. Root mean square deviation of celastrol/2Z63 was in the range of 1.8-4.8 Å. CONCLUSION: In particular, Glu376 of TLR4 receptor is crucial for the identification and binding of lipopolysaccharides (LPS), which are part of Gram-negative bacteria's outer membrane. In our investigation, celastrol binds to Glu376, suggesting that celastrol may prevent the dry eye syndrome by inhibiting LPS's binding to TLR4.

Photonic Weyl Waveguide and Saddle-Chips-like Modes.

Topological Weyl semimetals are characterized by open Fermi arcs on their terminal surfaces, these materials not only changed accepted concepts of the Fermi loop but also enabled many exotic phenomena, such as one-way propagation. The key prerequisite is that the two terminal surfaces have to be well separated, i.e., the Fermi arcs are not allowed to couple with each other. Thus, their interaction was overlooked before. Here, we consider coupled Fermi arcs and propose a Weyl planar waveguide, wherein we found a saddle-chips-like hybridized guiding mode. The hybridized modes consist of three components: surface waves from the top and bottom surfaces and bulk modes inside the Weyl semimetal. The contribution of these three components to the hybridized mode appears to be z-position-dependent rather than uniform. Beyond the conventional waveguide framework, those non-trivial surface states, with their arc-type band structures, exhibit strong selectivity in propagation direction, providing an excellent platform for waveguides. Compared with the conventional waveguide, the propagation direction of hybridized modes exhibits high z-position-dependency. For example, when the probe plane shifts from the top interface to the bottom interface, the component propagating horizontally becomes dimmer, while the component propagating vertically becomes brighter. Experimentally, we drilled periodic holes in metal plates to sandwich an ideal Weyl meta-crystal and characterize the topological guiding mode. Our study shows the intriguing behaviors of topological photonic waveguides, which could lead to beam manipulation, position sensing, and even 3D information processing on photonic chip. The Weyl waveguide also provides a platform for studying the coupling and the interaction between surface and bulk states.

Head rotation and the perception of eyelid height and contour.

PURPOSE: Effective visual perceptual processing is one of the many components of surgical competence. Human face identification is most efficient when viewed upright. However, it is not yet clear how this perception sensitivity impacts eyelid symmetry. This study investigates surgeons' and laypeople's accuracy and efficiency in perceiving eyelid asymmetry from different spatial perspectives. METHODS: A prospective psychometric experiment was conducted where oculoplastic surgeons were recruited from the American Society of Ophthalmic Plastic and Reconstructive Surgery and the Brazilian Oculoplastic Surgery Society, and control participants were recruited via crowdsourcing (Amazon's Mechanical Turk). Standard illustrations of the human face with varying degrees of eyelid abnormality, laterality, gender and rotation were presented to participants who were asked to judge whether the eyelids were symmetric or asymmetric. RESULTS: The survey was completed by 75 oculoplastic surgeons (49.33% male; mean age of 46.9±10.7) and 192 lay individuals (54.6% male; mean age 34.6±11.3 years). Among oculoplastic surgeons, deviation from upright was significantly associated with increased reaction time and decreased proportion correct (OR per 45° for peak 0.68, 95% CI 0.60 to 0.77, p<0.001; OR per 45° for ptosis 0.52, 95% CI 0.32 to 0.87, p=0.012; OR per 180° for aggregate responses 0.56, 95% CI 0.51 to 0.61, p<0.001). Oculoplastic surgeons demonstrated increasing accuracy and decreasing reaction time with additional trials for both peak and ptosis. CONCLUSION: Oculoplastic surgeons perceive eyelid asymmetries more accurately and can better compensate for inverted sensory information. However, accuracy increases and reaction time decreases with additional trials, suggesting trainability and potential for improvement in inversion disability.

Orbital and periocular complications in patients with sinonasal tumours with orbital invasion.

AIMS: The purpose of this study was to determine the frequency and associated risk factors of orbital/periocular complications in patients with sinonasal tumour with orbital invasion managed with eye-sparing treatments. METHODS: A retrospective case series of patients with primary sinonasal tumour with orbital invasion from January 2008 to December 2018. Patient factors were compared between the following groups: (1)patients with orbital/periocular complications versus those who did not and (2) patients who needed secondary oculoplastic surgical procedures versus those who did not. RESULTS: Out of 80 patients, 48 had eye-sparing surgery, 8 had orbital exenteration and 24 were managed non-surgically. The most common histology was squamous cell carcinoma (n=28, 35%). Among the eye-sparing treatment group, 51/72 patients experienced one or more orbital/periocular complication(s), with motility deficit (N=26, 36%) being the most frequent. Factors associated with higher risk of complications included tumour involving the orbital floor (p=0.019), clinical disease stage III/IV (p=0.038), maxillectomy (p=0.004), resection of the orbital floor (p=0.027) and cigarette smoking (p=0.041). Tumour involving the orbital floor had an OR of 3.9 (95% CI 1.3 to 11.6, p=0.016) in predicting orbital/periocular complication. In the eye-sparing surgery group, the most frequent secondary oculoplastic procedures was dacryocystorhinostomy (n=6, 13%). The use of a free flap in reconstruction had an OR of 8.2 (95% CI 2.1 to 31.8, p=0.002) in predicting need for secondary oculoplastic surgery. CONCLUSION: Majority of patients with sinonasal tumours and secondary orbital invasion were managed with eye-sparing multidisciplinary treatments. Preservation of the eye can lead to reasonably good functional outcome despite expected orbital and periocular complications.

Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III).

BACKGROUND: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. METHODS: Prospective observational multicentre study. All new referrals with diagnosis of GO within September-December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. RESULTS: Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0-350) vs 6 (0-552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). CONCLUSION: GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment.

Lower eyelid lengthening in facial nerve palsy: when is a periosteal flap required?

BACKGROUND/AIMS: To present a case series of patients with facial nerve palsy (FNP) undergoing lower eyelid surgery where inadequate horizontal tarsal length was encountered and managed with a periosteal flap. METHODS: A two-centre retrospective, non-comparative case series of all patients with FNP who underwent lower eyelid periosteal flap procedures. Theatre records identified all such procedures performed by, or under the supervision of, one of two surgeons (RM, BCP) between November 2018 and November 2020. Outcome measures, including the Cornea, static Asymmetry, Dynamic function, Synkinesis grading score, were measured preoperatively and postoperatively. RESULTS: All 17 patients had undergone medial canthal tendon (MCT) plication. Six had previously undergone MCT plication then were listed for further lower eyelid surgery. In 11 cases, horizontal deficiency was encountered intraoperatively, immediately following MCT plication. Four patients were surgery-naïve. 94% were within the 'contraction phase' of FNP (ie, greater than 1-year duration); eight (45%) had previously undergone lower eyelid shortening procedures (such as lateral tarsal strip procedure, LTS). All patients had improved lower eyelid position postoperatively, although at 1-year postoperation, four patients require redo lower eyelid surgery. CONCLUSIONS: MCT plication and stabilisation appear to be closely linked to the need for lower eyelid lengthening procedures, particularly in patients who have also undergone LTS and/or those within the 'contraction phase' of FNP. Unnecessary loss of horizontal tarsal length (particularly during LTS procedures) must be avoided in patients with FNP. Surgeons managing such patients should take care to identify inadvertent eyelid shortening early and be prepared to perform a lateral periosteal flap when required.

Subclinical Upper Eyelid Ptosis in Asian Patients: The Role of Levator Advancement in Optimizing Outcomes in "Cosmetic" Upper Blepharoplasty.

BACKGROUND: Subclinical ptosis is prevalent in Asian patients presenting for aesthetic upper blepharoplasty. To achieve predictable and satisfactory results in these patients, addressing the ptosis component is critical. In this paper, we present a precision levator advancement technique that enabled us to predictably incorporate the levator advancement into our upper blepharoplasty to deliver more predictable results in these patients. MATERIALS AND METHODS: Asian patients with normal or near normal margin to reflex distance 1 (MRD 1 of ≥ 3.5 mm) and symptoms and signs of straining of the frontalis with eyelid opening were diagnosed with subclinical upper eyelid ptosis and included in this prospective study. The advancement required was estimated pre-operatively using a formula that we developed. Our surgical technique is presented in detail here, and our long-term results were analysed. RESULTS: From December 2019 to August 2022, 97 patients were included in this study. Sixty-five patients were primary cases and 32 were revision cases. The mean follow-up was 15 months. Of the 192 eyelids analysed, our formula was able to correctly identify the required fixation location in 69% of eyelids. In majority of the eyelids (94%), the correct location of fixation location within +/- 1 mm of the estimated location. All patients (100%) were satisfied with their long-term results. Our revision rate was 3%. CONCLUSIONS: Incorporating a precisely done levator advancement into the upper blepharoplasty in patients with subclinical ptosis is critical for optimizing the aesthetic and functional outcomes. This approach has enabled us to perform this procedure greater predictably in this group of patients. LEVEL OF EVIDENCE III: 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 .

Hypochlorous acid hygiene solution in patients affected by blepharitis: a prospective randomised study.

BACKGROUND/AIMS: To investigate the clinical outcomes and antimicrobial activity of an hypochlorous acid hygiene solution compared with hyaluronic acid wipes for blepharitis treatment in patients with dry eye disease (DED). METHODS: This study involved 48 eyes of 48 patients affected by blepharitis with mild to moderate DED. 24 patients were treated with a hypochlorous acid hygiene solution (HOCL group) and 24 patients were treated with hyaluronic acid wipes (HYAL group) for a period of 4 weeks. The following clinical outcomes were assessed before (V0) and after the treatment period (V1): non-invasive keratograph break up time (NIK-BUT), tear film BUT (TF-BUT) tear meniscus height (TMH), Keratograph meibography, Meibomian Gland Yield Secretion Score (MGYSS), Corneal Staining Score (CSS), Schirmer test I, Keratograph conjunctival redness score and Ocular Surface Disease Index (OSDI). Moreover, microbiological analysis of upper and lower eyelid margins was performed at V0 both before and 5 min after treatment. RESULTS: After 1-month NIK-BUT and TF-BUT significantly increased in HOCL group, while they did not show a statistically significant difference in HYAL group compared with baseline. OSDI, TMH and MGYSS showed a significant difference in both groups, while Schirmer test, meibography, CSS and conjunctival redness score did not significantly change in both groups. Bacterial load showed a significant reduction in both groups, more pronounced in HOCL group compared with HYAL group. CONCLUSIONS: Hypochlorous acid hygiene solution can be securely employed in blepharitis treatment considering the satisfying clinical outcomes and antimicrobial activity compared with hyaluronic acid wipes.

Levodopa-Induced Dyskinesias in Parkinson's Disease: An Overview on Pathophysiology, Clinical Manifestations, Therapy Management Strategies and Future Directions.

Since its first introduction, levodopa has become the cornerstone for the treatment of Parkinson's disease and remains the leading therapeutic choice for motor control therapy so far. Unfortunately, the subsequent appearance of abnormal involuntary movements, known as dyskinesias, is a frequent drawback. Despite the deep knowledge of this complication, in terms of clinical phenomenology and the temporal relationship during a levodopa regimen, less is clear about the pathophysiological mechanisms underpinning it. As the disease progresses, specific oscillatory activities of both motor cortical and basal ganglia neurons and variation in levodopa metabolism, in terms of the dopamine receptor stimulation pattern and turnover rate, underlie dyskinesia onset. This review aims to provide a global overview on levodopa-induced dyskinesias, focusing on pathophysiology, clinical manifestations, therapy management strategies and future directions.

Immune checkpoint inhibitors for treatment of periorbital squamous cell carcinoma.

PURPOSE: To report on the outcomes of immunotherapy in patients with locally advanced periorbital squamous cell carcinoma. METHODS: We performed a retrospective chart review of seven consecutive patients with locally advanced periorbital cutaneous squamous cell carcinoma treated with anti-PD-1 immunotherapy. Treatments and therapeutic outcomes were reviewed. RESULTS: Of the seven patients, six were treated with cemiplimab, and one was treated with pembrolizumab. Five patients were treated with immunotherapy as neoadjuvant therapy before planned surgical resection; two patients received immunotherapy for treatment of advanced recurrent lesions deemed unresectable following multiple previous excisions and radiation therapy. In all seven patients, measurable clinical and/or radiologic response was observed. CONCLUSIONS: Our findings support the emerging role of anti-PD-1 immunotherapy in the management of locally advanced periorbital cutaneous squamous cell carcinoma.

Intraepithelial growth pattern for eyelid sebaceous carcinoma: a cohort of 214 patients from a single institution.

AIMS: To determine the distribution of three different intraepithelial growth patterns (pagetoid, bowenoid and papillary) in eyelid sebaceous carcinoma (SC) and correlate them with the clinical characteristics and prognosis. METHODS: A retrospective cohort study. The medical charts and pathological sections were retrospectively reviewed. All eligible patients were followed up for recurrence, metastasis and tumour-related mortality. The clinical significance of each intraepithelial growth pattern was determined by Cox regression. RESULTS: Of the 214 patients, 67 (31%) presented with intraepithelial invasion, among them, 34 (16%) were pagetoid, 27 (13%) were bowenoid and 6 (2.8%) were papillary. Patients of pagetoid intraepithelial spread showed significantly longer diagnostic delay (p=0.001) and more initial misdiagnoses of blepharitis (p=0.035). After a median follow-up period of 34.0 months, 67 (46%) patients in the non-intraepithelial group, 17 (50%) in the pagetoid group, 8 (30%) in the bowenoid group and 2 (33%) in the papillary group recurred. And 30 (20%) patients in the non-intraepithelial group, 9 (27%) in the pagetoid group and 4 (15%) in the bowenoid group developed metastasis. Moreover, 15 (10%) patients in the non-intraepithelial group, 6 (18%) in the pagetoid group and 1 (3.7%) in the bowenoid group died of SC. Cox regression indicated that pagetoid intraepithelial growth pattern was remarkably associated with increased chances of tumour-related mortality (HR=2.95, 95% CI 1.14 to 7.64, p=0.026). CONCLUSIONS: Intraepithelial tumour invasion was presented in nearly one third of patients with eyelid SC. Pagetoid intraepithelial neoplasia, the predominant growth pattern, significantly increased the risk of tumour-related mortality. Meticulous histopathological intraepithelial examination is recommended for every patient of eyelid SC. Special attention should be paid to those with pagetoid invasion, who may require more intensive managements.

Bézier curves as a total approach to measure the upper lid contour: redefining clinical outcomes in palpebral surgery.

AIMS: To define and quantify the upper lid contour by adapting Bézier curves with a newly developed software in normal subjects, assessing their reliability. METHODS: Fifty eyes of 50 healthy patients with no ocular pathology were included in this study from October 2020 to November 2020. All measurements were performed on Bézier curves adjusted to the upper lid contour. An original software was used to measure the radial and vertical midpupil-to-lid margin distances (MPLD), temporal-to-nasal (T/N) ratios, contour peak location and grade of superposition (GS) and asymmetry (GA) indexes. We calculated differences in the variables measured regarding age, gender or the side of the eye being assessed. RESULTS: The mean Bézier curve showed an excellent level of inter-rater reliability (intraclass correlation coefficient of 0.99). The median GS index of each eyelid to the mean Bézier curve was 95.4%, 8.5 IQR, and the median GA index was 3%, 3.4 IQR. The mean contour peak location was -0.35 mm, SD 0.45. Overall, the mean central MPLD was 4.1 mm, SD 0.6. No significant differences were found between male and female patients in variables derived from Bézier curves. CONCLUSION: Bézier curves may become a very useful tool for the assessment of upper lid contour, contour peak and symmetry. GS and GA indexes, along with the T/N area ratio are potential outcomes for this purpose. All current variables can be obtained just from one single Bézier curve measurement. Our results offer an in-depth exhaustive description of these variables and their distribution in the normal population.

Treatment strategies and long-term outcomes in patients with congenital microphthalmia-anophthalmia with cyst.

BACKGROUND/AIMS: Microphthalmia and anophthalmia are rare conditions, which represent ocular maldevelopment; both may be associated with orbital cysts. Current literature recommends retention to stimulate orbital growth during socket rehabilitation but does not illustrate their potential to deform the periocular tissues. This study aims to illustrate the long-term outcomes when other elements, such as forniceal and lid development, are also considered when formulating bespoke treatment plans for patients. METHODS: Retrospective case series of 78 patients attending a single prosthetics clinic between 1988 and 2020. Clinical and surgical notes, radiological imaging, clinical photographs and patient/doctor satisfaction questionnaires were used to report patient outcomes and natural history data. RESULTS: 89 sockets of 78 patients (11 bilateral) were included; average age of presentation being 2.8 years (9 days to 29.5 years). Cysts were clinically detected (48%) or were incidental findings (52%). The mean follow-up time was 7.2 years (6 months to 28 years). Cysts in 46% of sockets underwent surgical excision while the remainder were retained. Satisfaction surveys were obtained for 75 patients, with cosmetic outcomes rated as 'excellent' or 'good' in 90% of cases by physicians and 97% of cases by patients or guardians. CONCLUSION: The favourable long-term outcomes in this study have resulted from bespoke plans which considered periocular tissue development, regional orbital growth and orbital volume replacement. The authors contemplate cyst excision if the prosthetic fitting or retention is impeded by the cyst as this often heralds the increased risk of long-term periocular distortion.

Effect of eyelid muscle action and rubbing on telemetrically obtained intraocular pressure in patients with glaucoma with an IOP sensor implant.

BACKGROUND: Patients with glaucoma on topical glaucoma medication are often affected by dry eye symptoms and thus likely to rub or squeeze their eyelids. Here, we telemetrically measure peak intraocular pressure (IOP) during eyelid manoeuvres and eyelid rubbing. METHODS: Eleven patients with primary open-angle glaucoma (POAG) previously implanted with a telemetric IOP sensor (Eyemate-IO) were instructed to look straight ahead for 1 min as a baseline measurement. Next, 6 repeats of blinking on instruction with 10 s intervals in between were performed. In addition, 5 repeats of eyelid closure (n=9), eyelid squeezing and eyelid rubbing (n=7) were performed with 15 s intervals in between. IOP was recorded via an external antenna placed around the study eye. Average peak IOP increases from baseline were analysed and tested against zero (no change) with one-sample t-tests. RESULTS: For eyelid rubbing, the average peak ∆ IOP increase (mean±SEM) was 59.1±9.6 mm Hg (p<0.001) from baseline. It was 42.2±5.8 mm Hg (p<0.0001) for eyelid squeezing, 3.8±0.6 mm Hg (n=9, p<0.01) for eyelid closure and 11.6±2.4 mm Hg (p<0.001) for voluntary blinking. No IOP change except for a short irregularity in the ocular pulse was observed during involuntary blinking. CONCLUSION: Eyelid manoeuvres in patients with POAG elicited brief increases in IOP that were particularly large with squeezing and rubbing. Further investigation of the potential implications for glaucoma progression is warranted.

Specific location of ocular adnexal lymphoma and mortality: an international multicentre retrospective study.

AIMS: To examine whether the specific location of ocular adnexal lymphoma (OAL) and the American Joint Committee on Cancer (AJCC) TNM tumour stage are prognostic factors for mortality in the main OAL subtypes. METHODS: Clinical and survival data were retrospectively collected from seven international eye cancer centres. All patients from 1980 to 2017 with histologically verified primary or secondary OAL were included. Cox regression was used to compare the ocular adnexal tumour locations on all-cause mortality and disease-specific mortality. RESULTS: OAL was identified in 1168 patients. The most frequent lymphoma subtypes were extranodal marginal zone B-cell lymphoma (EMZL) (n=688, 59%); follicular lymphoma (FL) (n=150, 13%); diffuse large B-cell lymphoma (DLBCL) (n=131, 11%); and mantle cell lymphoma (MCL) (n=89, 8%). AJCC/TNM tumour-stage (T-stage) was significantly associated with disease-specific mortality in primary ocular adnexal EMZL and increased through T-categories from T1 to T3 disease. No associations between AJCC/TNM T-stage and mortality were found in primary ocular adnexal FL, DLBCL, or MCL. EMZL located in the eyelid had a significantly increased disease-specific mortality compared with orbital and conjunctival EMZL, in both primary EMZL and the full EMZL cohort. In DLBCL, eyelid location had a significantly higher disease-specific mortality compared with an orbital or lacrimal gland location. CONCLUSION: Disease-specific mortality is associated with AJCC/TNM T-stage in primary ocular adnexal EMZL patients. Lymphoma of the eyelid has the highest disease-specific mortality in primary EMZL, and in the full cohort of EMZL and DLBCL patients.

Diffuse pattern, orbital invasion, perineural invasion and Ki-67 are associated with nodal metastasis in patients with eyelid sebaceous carcinoma.

BACKGROUND: Metastasis 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. METHODS: A 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. RESULTS: Forty 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, p<0.001) were identified as independent risk factors for nodal metastasis. A nomogram that integrated these four factors had a C-index of 0.785, demonstrating a strong power in predicting nodal metastasis of eyelid SC. CONCLUSIONS: We 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.

Dacryolithiasis diagnosis and treatment: a 25-year experience using nasal endoscopy.

BACKGROUND: Dacryolith-induced epiphora is caused by a chronic obstruction of the nasolacrimal duct whose aetiology is often specified peroperatively. Dacryocystorhinostomy (DCR) has been often regarded as the gold standard to treat dacryolithiasis. Hasner's valve (HV) incision is a technique to evacuate lithiasis through its physiological track. The purpose of this study was to describe clinical and radiological findings associated with presence of dacryoliths in patients who underwent surgery and to assess the efficacy of these two procedures. METHODS: This study was a comparative interventional multicentric retrospective study including patients referred for an epiphora. The primary endpoint was to determine clinical and endoscopic findings associated with dacryoliths. The secondary endpoints were to evaluate the performance of CT dacryocystography (CT-DG) in the diagnosis of dacryoliths and the success rate of the surgical treatment 6 months postoperatively. RESULTS: 4677 nasolacrimal ducts (NLDs) (78.0% female, mean age 59.2) were included in the study. 3913 underwent DCR, and 764 underwent HV incision. 291 out of 4677 NLDs (6.2%) were found to have dacryoliths. Presence of mucocele associated to a permeable lacrimal system (OR 8.17 (95% 4.62 to 14.44), p<0.01) was associated with presence of lithiasis peroperatively. Success rates at 6 months were 95.6% for endonasal DCR and 94.6% for incision of HV in dacryolithiasis group (p<0.01). CT-DG had a negative predictive value of 96.3% to detect lithiasis (p<0.01). CONCLUSION: Strong clinical and endoscopic findings may improve the imputability of dacryoliths in epiphora. Evacuation of dacryolithiasis through its physiological track was first described in this study in adults with similar results to DCR in patients presenting with dacryolithiasis.

Selective activation of striatal indirect pathway suppresses levodopa induced-dyskinesias.

Levodopa (L-DOPA) administration remains the gold standard therapy for Parkinson's disease (PD). Despite several pharmacological advances in the use of L-DOPA, a high proportion of chronically treated patients continues to suffer disabling involuntary movements, namely, L-DOPA-induced dyskinesias (LIDs). As part of the effort to stop these unwanted side effects, the present study used a rodent model to identify and manipulate the striatal outflow circuitry responsible for LIDs. To do so, optogenetic technology was used to activate separately the striatal direct (D1R- expressing) and indirect (D2R- expressing) pathways in a mouse model of PD. Firstly, D1-cre or A2a-cre animals received unilateral injections of neurotoxin 6-hydroxydopamine (6-OHDA) to simulate the loss of dopamine observed in PD patients. The effects of independently stimulating each pathway were tested to see if experimental dyskinesias could be induced. Secondly, dopamine depleted A2a-cre animals received systemic L-DOPA to evoke dyskinetic movements. The ability of indirect pathway optogenetic stimulation to suppress pre-established LIDs was then tested. Selective manipulation of direct pathway evoked optodyskinesias both in dopamine depleted and intact animals, but optical inhibition of these neurons failed to suppress LIDs. On the other hand, selective activation of indirect striatal projection neurons produced an immediate and reliable suppression of LIDs. Thus, a functional dissociation has been found here whereby activation of D1R- and D2R-expressing projection neurons evokes and inhibits LIDs respectively, supporting the notion of tight interaction between the two striatal efferent systems in both normal and pathological conditions. This points to the importance of maintaining an equilibrium in the activity of both striatal pathways to produce normal movement. Finally, the ability of selective indirect pathway optogenetic activation to block the expression of LIDs in an animal model of PD sheds light on intrinsic mechanisms responsible for striatal-based dyskinesias and identifies a potential therapeutic target for suppressing LIDs in PD patients.