Atypical Spindle Cell and Pleomorphic Lipomatous Tumor of the Ocular Adnexa: Two Cases of a Rare Entity.

Atypical spindle cell and pleomorphic lipomatous tumor (ASCPLT) is a rare lipomatous neoplasm that was recently introduced into the World Health Organization Classification of Soft Tissue and Bone tumors as a distinct entity. ASCPLT has potential for local recurrence but does not metastasize. This biologic behavior separates ASCPLT from its morphologic mimics. Ocular adnexal ASCPLT has not been previously reported. Described herein are two patients with ASCPLT. The subcutaneous orbital rim lesion featured markedly pleomorphic spindle and multinucleated cells. The eyelid lesion was dominated by atypical spindle cells in a background of mature adipocytes. Both neoplasms demonstrated infiltrative margins, rare mitotic figures, immunoreactivity for CD34 and loss of Rb1, and the absence of MDM2 amplification by fluorescence in situ hybridization. Recognition of ASCPLT in the differential of ocular adnexal neoplasms may lead to a re-evaluation of morphologically similar tumors, which may have varied biologic behavior and warrant a different management approach.

Using three-dimensional printed models for trainee orbital fracture education.

BACKGROUND: Three-dimensional printing is an underutilized technology in ophthalmology training; its use must be explored in complex educational scenarios. This study described a novel approach to trainee education of orbital fracture repair utilizing three-dimensional (3D) printed models as a teaching tool. METHODS: Ophthalmology residents and oculoplastic fellows from multiple training institutions underwent an educational session on orbital fractures, learning through four different models. Participants analyzed orbital fractures through computerized tomography (CT) imaging alone and then utilizing CT imaging with the aid of a 3D printed model. Participants completed a questionnaire assessing their understanding of the fracture pattern and surgical approach. After the training, participants were surveyed on the impact of the educational session. Components of the training were rated by participants on a 5-point Likert scale. RESULTS: A statistically significant difference (p < .05) was found in participant confidence conceptualizing the anatomic boundaries of the fracture and planning the orbital fracture approach for repair of three out of four models on pre-test post-test analysis. On exit questionnaire, 84.3% of participants thought the models were a useful tool for surgical planning, 94.8% of participants thought the models were a useful tool for conceptualizing the anatomic boundaries of the fracture, 94.8% of participants thought the models were a useful tool for orbital fracture training, and 89.5% of participants thought the exercise was helpful. CONCLUSION: This study supports the value of 3D printed models of orbital fractures as an effective tool for ophthalmology trainee education to improve understanding and visualization of complex anatomical space and pathology. Given the limited opportunities trainees may have for hands-on orbital fracture practice, 3D printed models provide an accessible way to enhance training.

Correction of severe medial ectropion using a novel osseous fixation technique.

PURPOSE: To study the feasibility of osseous medial canthal fixation for severe medial ectropion. METHODS: Retrospective analysis over a period of 3 years identified 10 patients who had undergone the modified medial canthoplasty. Outcome measures were based on the presence of complications and cosmetic/functional results. RESULTS: Post-operative evaluations of all patients were significant for excellent functionality and cosmetic results in the medial canthal area following the novel osseous fixation technique. No complications were reported intra-operatively or post-operatively. CONCLUSIONS: For repair of severe medial ectropion, especially cicatricial and paralytic ectropion, the modified medial "puncture hole" canthoplasty is an effective alternative to traditional repair techniques and does not necessitate the use of anchoring systems such as wiring or microplates.

Adnexal squamous cell carcinoma: incidence of eyelid margin involvement.

PURPOSE: We aimed to perform a review of facial and periorbital squamous cell carcinoma (SCC) cases to assess the relative incidence of eyelid margin involvement. METHODS: This is a retrospective review of all patients with biopsy-proven SCC who were evaluated at a single oculoplastic surgery practice from 2007 to 2019. The charts were reviewed for the anatomical location of the malignancy, and those involving the eyelid were further divided into marginal and non-marginal lesions. Statistical analysis was performed using a one proportion z-test. RESULTS: A total of 76 patients with a diagnosis of biopsy-proven periorbital and facial SCC were identified, 67 involved the ocular adnexa. Thirty-nine (58.2%) patients had lesions located on the eyelid. Of these, 33 (84.6% p < 0.0001, 95% CI 69.45-94.13) had lesions located at the margin, six of the 39 lesions were non-marginal. The remaining lesions were present within the brow (n = 10, 14.9%), medial canthus (n = 10, 14.9%), palpebral conjunctiva (n = 1, 1.5%), or orbit (n = 1, 1.5%). In six patients (8.9%) lesions involved multiple anatomic subunits. CONCLUSION: We present our investigation of the incidence of SCC of the marginal vs. non-marginal eyelid, revealing a statistically significant increased involvement of the eyelid margin. Future investigations are necessary to further elucidate the vulnerability of the eyelid margin to the development of SCC in particular in regards to the role of the unique genetic expression profile of eyelash follicular stem cells.

N,N-Dimethyldithiocarbamate Elicits Pneumococcal Hypersensitivity to Copper and Macrophage-Mediated Clearance.

Streptococcus pneumoniae is a Gram-positive, encapsulated bacterium that is a significant cause of disease burden in pediatric and elderly populations. The rise in unencapsulated disease-causing strains and antimicrobial resistance in S. pneumoniae has increased the need for developing new antimicrobial strategies. Recent work by our laboratory has identified N,N-dimethyldithiocarbamate (DMDC) as a copper-dependent antimicrobial against bacterial, fungal, and parasitic pathogens. As a bactericidal antibiotic against S. pneumoniae, DMDC's ability to work as a copper-dependent antibiotic and its ability to work in vivo warranted further investigation. Here, our group studied the mechanisms of action of DMDC under various medium and excess-metal conditions and investigated DMDC's interactions with the innate immune system in vitro and in vivo. Of note, we found that DMDC plus copper significantly increased the internal copper concentration, hydrogen peroxide stress, nitric oxide stress, and the in vitro macrophage killing efficiency and decreased capsule. Furthermore, we found that in vivo DMDC treatment increased the quantity of innate immune cells in the lung during infection. Taken together, this study provides mechanistic insights regarding DMDC's activity as an antibiotic at the host-pathogen interface.

Potent Periorbital Fractionated CO 2 Laser Resurfacing.

BACKGROUND: The aged face results from a culmination of skin changes, gravitational descent, and volume loss. Surgical interventions in the periorbital region are beneficial for addressing these 3 factors. Despite this, studies describing CO2 laser safety settings are lacking. OBJECTIVE: There is no present consensus on ideal periorbital CO2 laser; therefore, this study evaluates the safety of periorbital laser resurfacing as an adjunct to lower blepharoplasty using robust settings. MATERIALS AND METHODS: A retrospective review was performed of all patients who underwent bilateral lower blepharoplasty with adjunctive periorbital (upper and lower eyelid) fractionated CO2 laser resurfacing from 2013 to 2018 performed by a single oculoplastic surgeon. RESULTS: Fifty-nine patients were included. Six patients experienced side effects including postinflammatory hyperpigmentation, (3/59, 5.1%), prolonged superficial excoriations (1/59, 1.7%), prolonged hyperemia (1/59, 1.7%), and lower eyelid retraction requiring lower eyelid recession (1/59, 1.7%). None of the patients developed postoperative infection. All patient expressed satisfaction at their final postoperative visit. CONCLUSION: CO2 laser resurfacing, even with robust settings, is a safe and effective adjunct to lower blepharoplasty.

5-Fluorouracil With Microneedling Modulates Wound Healing in a Murine Model: An Immunohistochemical Analysis of Mechanism and Dose Efficacy.

PURPOSE: The purpose of this study is to assess the dose-dependent immunohistopathological effects of intradermal microneedle-delivered 5-fluorouracil (5-FU) for postincisional wound healing in a murine model. METHODS: A prospective experimental study was performed. Twelve hairless mice were randomized into 4 treatment groups for postincisional wound treatment: microneedling with topical saline, or microneeding with topically-applied 5-FU at concentrations of 25 mg/ml, 50 mg/ml, or 100 mg/ml. Two surgical wounds were created on each animal. Combination wound treatments were performed on postoperative days 14 and 28, and cutaneous biopsies were obtained on day 56. Specimens were analyzed by a dermatopathologist, blinded to the treatment group, for collagen thickness, lymphocytic infiltration, histiocytic response, sub-epidermal basement membrane zone thickness, and myofibroblast density. RESULTS: Histopathologic evaluation showed increased collagen thickness, lymphocyte infiltration, and granuloma density in the groups undergoing microneedling treatment with 5-FU, compared to saline. Immunohistochemical analysis revealed a trend toward thicker basement membranes with higher concentrations of 5-FU used, reaching statistical significance between controls and those treated with 100 mg/ml 5-FU ( p = 0.0493). A trend toward decreasing myofibroblast density with increasing doses of 5-FU was noted. No postincisional or treatment complications were observed. CONCLUSIONS: Our results demonstrate that microneedling is an effective topical subepithelial drug delivery system, and further suggest a beneficial dose-dependent immunomodulatory effect of 5-FU on intermediate wound healing when used in combination with microneedling. We recommend a 5-FU dose at the mid-range 50 mg/ml concentration to simultaneously maximize efficacy and minimize complication risk.

An assessment of techniques and practices used to elevate intra-abdominal pressure when assessing pelvic floor dysfunction.

AIMS: To determine terminology and methods for raising intra-abdominal pressure (IAP) currently used by clinicians to assess pelvic floor dysfunction (PFD) and to measure the effect of these maneuvers on IAP. METHODS: Three-hundred questionnaires were distributed at two scientific meetings in the United Kingdom to determine methods clinicians used to raise IAP and their perceptions of these methods. Twenty healthy volunteers were also recruited to measure the effect of two methods of raising IAP: Valsalva maneuver (VM) and bear down maneuver (BDM). IAP pressure was measured with rectal catheters connected to pressure sensors. The IAP was measured during each maneuver in both standing and supine positions. RESULTS: Maneuvers used in practice were cough (79%), BDM (60%), and VM (38%). 44% of clinicians felt patients found it difficult to raise their IAP. There was uncertainty among clinicians as to which method was the most effective in raising IAP and whether the different methods produced the same rise in IAP. On testing IAP in 20 healthy volunteers, median (interquartile range) IAP generated during BDM; 101 (59.1) cmH2 O was significantly higher than that generated during VM; 80.3 (43.6) cmH2 O (p < .0001). CONCLUSION: Clinicians varied widely in the maneuvers they used to raise patients' IAP to test for PFD and there was uncertainty about the maneuvers' effect on IAP. In healthy volunteers, BDM produced significantly higher IAP than VM. We recommend standardization of terminology and techniques used to raise IAP when assessing PFD, to ensure consistency of diagnosis and assessment of treatment outcomes.

Wound Dehiscence Following Upper Blepharoplasty: A Review of 2,376 Cases.

PURPOSE: There have been limited studies evaluating specifically the incidence of wound dehiscence following isolated upper blepharoplasty. This is a large-scale upper blepharoplasty review to evaluate the rate of wound dehiscence, to assess risk factors, and to analyze management outcomes. METHODS: A retrospective review was performed of all patients who underwent upper blepharoplasty at a single surgery center. All incisions were closed using either 6-0 fast-absorbing plain gut or polypropylene suture in a running fashion, with an additional interrupted suture near the lateral wound edge. Incidence of wound dehiscence was determined and further assessed by patient age (≤67 or >67 years), gender, preexisting medical conditions, smoking history, and suture type. RESULTS: A total of 1,190 patients (2,376 eyelids) met inclusion criteria. In total, there were 34 instances (1.4%) of wound dehiscence in 32 patients at an average 9 days (range, 0-30 days) following surgery. Evaluation of wound dehiscence rates by demographic factors revealed male gender to be a significant predictor of wound dehiscence (p = 0.0062). Age, hypertension, heart disease, and diabetes were not predictors of wound dehiscence. Lifetime smoking history increased risk for wound dehiscence (p < 0.0001). Use of fast-absorbing plain gut suture was also significantly associated with dehiscence, when compared with polypropylene (p = 0.0025). Multivariate analysis revealed male gender and fast-absorbing plain gut suture to be independent risk factors for wound dehiscence. Seventeen eyelids with wound separation were observed for second-intention healing, 1 underwent delayed scar revision. Fourteen eyelids were repaired primarily using suture and 3 with cyanoacrylate surgical skin adhesive. All patients reported satisfaction with their final outcome, and objective final healing was deemed satisfactory. CONCLUSIONS: Wound dehiscence following isolated upper blepharoplasty is rare and associated with male gender and fast-absorbing plain gut suture. Patients with wound separation may be successfully managed with individualized care.

The Community In-reach Rehabilitation and Care Transition (CIRACT) clinical and cost-effectiveness randomisation controlled trial in older people admitted to hospital as an acute medical emergency.

Objective: To compare the clinical and cost-effectiveness of a Community In-reach Rehabilitation and Care Transition (CIRACT) service with the traditional hospital-based rehabilitation (THB-Rehab) service. Design: Pragmatic randomised controlled trial with an integral health economic study. Settings: Large UK teaching hospital, with community follow-up. Subjects: Frail older people aged 70 years and older admitted to hospital as an acute medical emergency. Measurements: Primary outcome: hospital length of stay; secondary outcomes: readmission, day 91-super spell bed days, functional ability, co-morbidity and health-related quality of life; cost-effectiveness analysis. Results: A total of 250 participants were randomised. There was no significant difference in length of stay between the CIRACT and THB-Rehab service (median 8 versus 9 days; geometric mean 7.8 versus 8.7 days, mean ratio 0.90, 95% confidence interval (CI) 0.74­1.10). Of the participants who were discharged from hospital, 17% and 13% were readmitted within 28 days from the CIRACT and THB-Rehab services, respectively (risk difference 3.8%, 95% CI −5.8% to 13.4%). There were no other significant differences in any of the other secondary outcomes between the two groups. The mean costs (including NHS and personal social service) of the CIRACT and THB-Rehab service were £3,744 and £3,603, respectively (mean cost difference £144; 95% CI −1,645 to 1,934). Conclusion: The CIRACT service does not reduce major hospital length of stay nor reduce short-term readmission rates, compared to the standard THB-Rehab service; however, a modest (<2.3 days) effect cannot be excluded. Further studies are necessary powered with larger sample sizes and cluster randomisation. Trial registration: ISRCTN 94393315, 25th April 2013

Thyroid Eye Disease: Pilot Study Comparison Between Patients in United States-Based and India-Based Practices.

PURPOSE: Thyroid eye disease (TED) phenotype varies by ethnicity/race and genetic/environmental factors. This study compared demographic and clinical characteristics of TED patients from the US and India. DESIGN: Observational pilot study . METHODS: Sixty-four patients with TED ages ≥18 years old with active disease (onset of symptoms ≤18 months or presenting clinical activity score (CAS) ≥4) were recruited between March and October 2021 from clinical practices in the United States (Philadelphia, PA) (n = 30) and India (Hyderabad, India) (n = 34). Data collection at baseline and 3 months included clinical measurements, thyroid disease history, and photographs. Ocular symptoms and quality of life data were obtained by phone interview. CAS was calculated using the standard 7-point scale. RESULTS: There was no statistically significant difference in age, TED duration, or smoking status between patient groups. Both groups had good vision, a low rate of optic neuropathy, and comparable exophthalmometry. US patients were predominantly female (86.7% [26/30]), with a history of hyperthyroidism (96% 29/30). In comparison, Indian patients were 52.9% (18/34, P = .004) female; underlying thyroid disease was distributed between hyperthyroidism (52%), hypothyroidism (17.6%) and euthyroid (9.7%). Mean (SD) CAS in the US cohort was double the score in the India cohort (4.2 (1.7) vs 1.65 (1.7), respectively) (P < .0001). However, patients at both sites experienced subjective symptoms of TED at a similar frequency. CONCLUSIONS: Observed differences in TED between US and Indian patients warrant further investigation to elucidate differences in pathogenesis, disease expression, or other factors that may influence TED in diverse populations.

Toxoplasma type II effector GRA15 has limited influence in vivo.

Toxoplasma gondii is an intracellular parasite that establishes a long-term infection in the brain of many warm-blooded hosts, including humans and rodents. Like all obligate intracellular microbes, Toxoplasma uses many effector proteins to manipulate the host cell to ensure parasite survival. While some of these effector proteins are universal to all Toxoplasma strains, some are polymorphic between Toxoplasma strains. One such polymorphic effector is GRA15. The gra15 allele carried by type II strains activates host NF-κB signaling, leading to the release of cytokines such as IL-12, TNF, and IL-1ß from immune cells infected with type II parasites. Prior work also suggested that GRA15 promotes early host control of parasites in vivo, but the effect of GRA15 on parasite persistence in the brain and the peripheral immune response has not been well defined. For this reason, we sought to address this gap by generating a new IIΔgra15 strain and comparing outcomes at 3 weeks post infection between WT and IIΔgra15 infected mice. We found that the brain parasite burden and the number of macrophages/microglia and T cells in the brain did not differ between WT and IIΔgra15 infected mice. In addition, while IIΔgra15 infected mice had a lower number and frequency of splenic M1-like macrophages and frequency of PD-1+ CTLA-4+ CD4+ T cells and NK cells compared to WT infected mice, the IFN-γ+ CD4 and CD8 T cell populations were equivalent. In summary, our results suggest that in vivo GRA15 may have a subtle effect on the peripheral immune response, but this effect is not strong enough to alter brain parasite burden or parenchymal immune cell number at 3 weeks post infection.

Post-Operative Endonasal Debridement May Improve Outcomes of Endoscopic Dacryocystorhinostomy.

Background: Endoscopic dacryocystorhinostomy (endoDCR) has proven to be an effective minimally invasive surgical procedure for treatment of nasolacrimal duct obstruction. Post-surgical endonasal debridement has not yet been independently assessed for its impact on functional success. Methods: A retrospective review was performed of all patients who underwent endoDCR by an experienced oculofacial plastic surgeon over 7 years (2012-2019). Post-operative intranasal debridement was not routinely performed from March 2012 to February 2016. From March 2016 to June 2019, all patients underwent routine ipsilateral intranasal debridement at post-operative week 2. Surgical success was determined based upon subjective assessment of epiphora resolution at the patient's final post-operative visit. Results: A total of 69 patients (88 surgeries) were included. Thirty-five patients had standard post-operative follow-up without debridement, whereas 34 underwent endonasal debridement at post-operative week 2. Demographics and follow-up were similar between the 2 groups. Functional success was achieved in 84.1% of patients without debridement, and in 97.7% with debridement (P = .058). Conclusion: This review demonstrates a trend toward improvement in the rate of surgical success of endoDCR when routine endonasal debridement was instituted 2 weeks following surgery. We believe that removal of nasal crusts, clots, and residual absorbable gelatin sponge at the osteotomy site improves tear outflow and reduces cicatricial healing enhancing patency of the surgically derived lacrimal-nasal fistula. We advocate for postoperative debridement in the perioperative management of endoDCR patients to optimize successful outcomes.

Postoperative diplopia after medial-inferior orbital wall decompression in patients with thyroid eye disease.

KEY POINTS: 10% of patients undergoing MAI decompression for TED developed new-onset diplopia MAI decompression remains an excellent option for orbital decompression for TED.

The placebo effect: advances from different methodological approaches.

There is accumulating evidence from different methodological approaches that the placebo effect is a neurobiological phenomenon. Behavioral, psychophysiological, and neuroimaging results have largely contributed to accepting the placebo response as real. A major aspect of recent and future advances in placebo research is to demonstrate linkages between behavior, brain, and bodily responses. This article provides an overview of the processes involved in the formation of placebo responses by combining research findings from behavioral, psychophysiological, and neuroimaging methods. The integration of these different methodological approaches is a key objective, motivating our scientific pursuits toward a placebo research that can inform and guide important future scientific knowledge.

Role of functional brain imaging in understanding rheumatic pain.

Rheumatic pain and, in particular, rheumatoid arthritis, osteoarthritis and fibromyalgia, are common and debilitating chronic pain syndromes. Recently, human functional neuroimaging, for example EEG, fMRI, and PET has begun to reveal some of the crucial central nervous system mechanisms underlying these diseases. The purpose of this review is to summarise current knowledge on the brain mechanisms of rheumatic pain revealed by functional neuroimaging techniques. The evidence suggests that two mechanisms may be largely responsible for the clinical pain associated with these rheumatic diseases: abnormalities in the medial pain system and/or central nervous system sensitisation and inhibition. If we can understand how functioning of the central nociceptive system becomes altered, even in the absence of peripheral nociceptive input, by using functional neuroimaging techniques, in the future we may be able to develop improved, more effective treatments for patients with chronic rheumatic pain.