Teprotumumab in thyroid eye disease.

Thyroid eye disease (TED) is an inflammatory condition involving the periocular and orbital soft tissues, affecting most commonly patients with hyperthyroid disorders. Traditional treatments used for the active phase of the disease range from conservative lubrication for mild symptoms to systemic immunomodulating drugs for moderate-to-severe symptoms. Teprotumumab (Tepezza) is a monoclonal antibody with an inhibitory effect on insulin-like growth factor 1 and is the first Food and Drug Administration (FDA) approved targeted medical therapy for reducing the inflammatory signs and symptoms associated with TED. Two large multicenter, randomized, double-masked, placebo-controlled trials have confirmed the efficacy and safety of teprotumumab in patients with active, moderate-to-severe TED. Recent reports and publications have also demonstrated the efficacy of teprotumumab in a wider range of patients. In this review, we summarize the clinical features and pathophysiology of TED, disease course, and traditional management methods. We further detail the development of teprotumumab, the founding studies that brought it to its FDA approval, adverse events profile, and ongoing as well as future investigations.

Complete Response to Immunotherapy Using Pembrolizumab in a Patient With Conjunctival Squamous Cell Carcinoma With Nodal Metastasis.

A 92-year-old woman presented with a large bulbar conjunctival mass in the OD. She also had a palpable parotid mass which on fine needle aspiration biopsy confirmed to be metastatic squamous cell carcinoma. The conjunctival mass was biopsied to confirm the diagnosis of squamous cell carcinoma with positive programmed cell death ligand 1 expression and a high tumor mutation burden. She was treated with pembrolizumab and had complete resolution of the conjunctival mass and the associated parotid metastasis after just 2 cycles of treatment. This case underscores the promising role of immune checkpoint inhibitors in the treatment of conjunctival squamous cell carcinoma, especially when surgery is associated with significant ocular morbidity, in patients who may not be good surgical candidates, or in patients with metastasis.

Lacrimal Gland Adenocarcinoma Clinicopathologic Features and Outcomes Compared With Those of Lacrimal Gland Adenoid Cystic Carcinoma.

PURPOSE: Lacrimal gland (LG) adenocarcinomas (ACs) are rare, with limited data. We compared clinicopathologic features and local recurrence, distant metastasis, and survival rates between LG AC and LG adenoid cystic carcinoma (ACC). METHODS: The records of LG AC patients treated from 2008 to 2022 and LG ACC patients treated from 1998 to 2022 at the same center were retrospectively reviewed. RESULTS: The study included 20 patients with AC; 10 de-novo AC, 10 ex-pleomorphic AC; and 51 ACC patients. The median age at diagnosis was 61 years for de-novo AC, 54 years for ex-pleomorphic AC, and 45 years for ACC. All groups had male predominance. The initial T category was T2 in 50% (5/10) of de-novo ACs; 60% (6/10) of ex-pleomorphic ACs; and 59% (30/51) of ACCs. Perineural invasion was present in 33% (5/15) of ACs and 90% (45/50) of ACCs ( p < 0.001). Of the 20 AC patients, 14 had eye-sparing surgery; 4 had orbital exenteration; and 2 had unresectable disease. All AC patients received postoperative radiotherapy and 15 (75%) received concurrent chemotherapy. Fourteen AC patients were tested for human growth factor receptor 2 expression, and 10 (71%) were human growth factor receptor 2 positive; 5 received human growth factor receptor 2-targeted therapy. AC and ACC had similar 5-year recurrence rates (20% and 33%, respectively, p = 0.31) and metastasis rates (20% and 34%, respectively, p = 0.30). de-novo AC, ex-pleomorphic AC, and ACC had similar 5-year disease-specific survival rates (80%, 79%, and 81%, respectively, p > 0.99). CONCLUSIONS: LG AC and ACC have similar baseline clinicopathologic features, except that perineural invasion is more common in ACC, and similar recurrence, metastasis, and survival rates. Human growth factor receptor 2-targeted therapy may be appropriate in some patients with LG AC.

Long-term retinal changes after strabismus surgery, suspected signs of past scleral perforations.

Purpose: Scleral perforation during strabismus surgery is considered a rare complication that usually results in no significant consequences. The true rate of such occurrences is difficult to evaluate due to the young age of most patients and the occult nature of most events. This study aimed to evaluate long-term retinal changes under the suture areas in patients post-strabismus surgery as presumed signs indicating past undiscovered scleral perforations. Methods: The study population consisted of patients with a follow-up of at least 10 years post-strabismus surgery at the [redacted for review] Eye Institute and with no known retinal conditions as well as with wide fundus visibility. We performed slit-lamp retinal periphery examinations in search of retinal scars or changes at the suture sites. Results: Seventy-one eyes from 43 patients were examined. The mean age (±standard deviation [SD]) at the time of examination was 27 years (±14), and the mean number of strabismus surgeries per patient was 1.8. Three of the examined eyes showed retinal changes at the suture sites, yielding an overall incidence rate of suspected perforation/penetration of 4.2% per eye and 3.6% per strabismus surgery. These three patients were all asymptomatic. Conclusion: Scleral perforations during strabismus surgeries could remain unnoticed since a comprehensive exam of the retinal periphery is challenging in young children, especially during the postoperative period. While retinal changes caused by inadvertent scleral perforations appear to have no clinical sequelae in a time frame of 10 years, such changes should be noted for future fundoscopic examinations.

Peripapillary and fovea avascular zone optical coherence tomography angiography parameters in exfoliation glaucoma versus primary open-angle glaucoma versus healthy eyes.

Purpose: To examine the differences in the peripapillary vascular parameters and foveal-avascular-zone (FAZ) vascularity parameters between primary open-angle-glaucoma (POAG) patients versus exfoliation-glaucoma (XFG) patients versus healthy subjects. Methods: This is cross-sectional study and a comparative clinical study. POAG and XFG patients and healthy subjects underwent a comprehensive ophthalmic examination, including visual field optical coherence tomography (OCT) and OCT angiography (OCTA) of the optic disc and FAZ. Differences in peripapillary vessel density (VD), perfusion density (PD), and FAZ area and circularity were examined between all groups, as well as correlations between clinical parameters and vascularity parameters for each glaucoma group. Results: A total of 109 subjects (one eye for each patient) were analyzed, including 45 with POAG, 30 with XFG, and 34 controls. The average peripapillary VDs were the lowest among the XFG patients and the highest among the controls (P < 0.05, ANOVA). The average peripapillary PD of the central ring was the lowest in the XFG group and the highest in the control group (P = 0.02, ANOVA). A significant negative correlation was found between the average peripapillary VDs and PDs of the inner ring and full ring and disease severity of the POAG patients. There was a significant positive correlation between the average peripapillary PDs of the central rings and full ring and the central macular thickness of the XFG patients (P < 0.01 and P < 0.04, respectively, Pearson correlation). Conclusion: The peripapillary vascular parameters of the POAG and XFG patients were lower compared to those of normal participants. A correlation between clinical characteristics of POAG and XFG patients and PD was found. This may hint to a vascular mechanism in glaucoma either primary or secondary to intra-ocular pressure/OAG damage.

COVID-19's Influence on Ocular Emergency Visits at a Tertiary Referral Center and Its Relationship to Emergency Indications by the American Academy of Ophthalmology.

PURPOSE: To examine the trends of ocular emergency admissions during the COVID-19 pandemic at a tertiary care center. METHODS: The study's sample consisted of all patients who were seen in the ophthalmic emergency room (OER) between March 15 and April 15, 2020 (during the COVID-19 pandemic) and in the same time frame of the previous year. The cases were categorized as urgent vs. nonurgent according to the AAO urgency guidelines during the coronavirus period, and the ability to treat the case with telemedicine was evaluated retrospectively. RESULTS: A total of 553 patients were admitted to the OER during the pandemic period, whereas in the same time frame of the previous year, 1,069 were admitted. The female/male proportion was 526/543 (49.2%/50.8%) in 2019 and 258/259 (46.7%/53.3%) the following year. Age (years, average ± SD) was 44.7 ± 24.5 in 2019 and 47.9 ± 23.4 in 2020. There were more self-referrals in 2020 compared to 2019 (41.1% vs. 32.6%; p=0.0004). The time spent in the OER was reduced from 109 ± 74 (minutes, average ± SDV) in 2019 to 73 ± 51 in 2020 (p < 0.0001). The most common cause of OER examinations in 2020 was related to the posterior segment of the eye (23.9%), whereas infection and inflammation of the anterior segment were the most common causes in 2019 (35.5%). Urgency by AAO standards was in agreement in 26.7% admissions in 2019 and 35.6% in 2020 (p=0.0002). CONCLUSION: The COVID-19 pandemic has influenced several aspects of the OER, including the number of referrals, type of ophthalmic emergency, the time spent in the OER, and the need for emergent treatment. Our change in the treatment algorithm was in agreement with the AAO recommendations during the pandemic.

Ocular injuries incurred by Israeli defense forces during low-intensity conflicts.

BACKGROUND: To describe ocular injuries sustained by Israeli Defense Forces (IDF) soldiers during low-intensity conflicts from 1998 to 2017, and to evaluate the use of protective eyewear. METHODS: Retrospective analysis of data retrieved from two tertiary Israeli medical centers and the military trauma registry. The analysis included all IDF soldiers with ocular injuries who were referred to these centers between 1998 and 2017. Data on injury type, the use of protective eyewear, and interventions were retrieved and analyzed. Additional data regarding the use of protective eyewear and ocular injuries in 108 patients with head and neck injuries in one operation was analyzed. RESULTS: A total of 126 soldiers, all males, mean age 22 (SD 5.3) years, sustained ocular injuries during low-intensity conflicts and treated at one of the two participating medical centers. Blast was the most common type of injury (n = 70/126, 56%), followed by shrapnel (n = 37/126, 29%) and gunshot wound (n = 12/126, 9%). The Birmingham Eye Trauma Terminology System (BETTS) injury pattern disclosed lamellar laceration (n = 34/126, 27%), intraocular foreign body (n = 27/126, 21%), penetrating (n = 10/126, 8%), and perforating (n = 7/126, 6%) injuries. Average VA improved from 20/140 at presentation to 20/60 after surgical or conservative intervention, the median VA improved from 20/40 to 20/30 (P < 0.001). Forty-nine patients (49/126, 39%) had poor visual outcome. The mean follow-up lasted 22 (SD 31) months. The use of protective eyewear was correlated with better initial VA(20/30 vs 20/217, P = 0.07). Among 108 patients with head and neck injuries, there was a higher rate of ocular injuries in the group of patients who did not use protective eyewear (n = 26/73, 36% vs n = 4/35, 11%, P = 0.016). CONCLUSIONS: Ocular injuries are common occurrences in low-intensity conflicts. The use of protective eyewear significantly reduces these injuries and should be mandatory. LEVEL OF EVIDENCE: III, prognostic.

Kelly punch punctoplasty vs. simple punctal dilation, both with mini-monoka silicone stent intubation, for punctal stenosis related epiphora.

OBJECTIVES: To compare the outcomes of stenotic punctal dilation by means of a punctal dilator alone vs. a Kelly punch punctoplasty, both followed by insertion of a mini-monoka stent, for treatment of symptomatic punctal stenosis. METHODS: A retrospective, comparative study. The participants were patients with punctal stenosis related epiphora treated at the Goldschleger Eye Institute, Sheba Medical Center. All patients were treated either by simple punctal dilation (group 1) or Kelly punch-assisted punctoplasty (group 2), both followed by mini-monoka stent insertion. Symptoms relief and subjective epiphora scoring (Munk score) were compared and analysed. RESULTS: Fifty patients were included in the study; Mean age (+SD) of the participants was 60 years (±12, range 30-86 years). Baseline characteristics (age, gender distribution, and visual acuity) were similar in both groups. The mini-monoka stent was placed for an average period of 2 weeks, and all patients received postoperative steroids and antibiotic treatment for 1 week. The Munk score decreased significantly in both groups following the procedure, dropping from 4.9 to 1.9 in group 1 and from 4.3 to 1.2 in group 2 (P < 0.005 for both groups). There was no difference in the delta Munk score between the two groups. CONCLUSIONS: Simple punctal dilation followed by insertion of a mini-monoka stent is effective in alleviating the symptoms of punctal stenosis-related epiphora. There was no added benefit when the more invasive Kelly punch-assisted punctoplasty was used, raising some doubt about its justification in these cases.

Inadvertent corneal pigmentation following cosmetic blepharopigmentation.

PURPOSE: To present a case of inadvertent corneal pigmentation as a complication of cosmetic eyelid tattooing. OBSERVATIONS: A 63 year old woman presented with left eye redness and irritation 3 days after undergoing permanent eyeliner tattooing of her upper and lower eyelids. On ocular examination a black pigmentation of the nasal cornea in her left eye was observed, with associated conjunctival injection. Initial slit lamp attempts of pigment removal were unsuccessful. A surgical attempt to scrape the pigment in the stroma was only partially successful due to the penetration of pigment particles in between stromal lamellae. Microanalysis spectroscopy was performed on a specimen of pigment taken from the eyelashes in order to attain the chemical properties of the material and assist with further therapeutic strategy. The analysis revealed an organic inert nature of the material (mostly carbon and oxygen) and ruled out presence of dangerous components such as copper and lead. Due to minimal inflammatory reaction and the non-central location of the corneal pigmentation, the patient remained under close observation, treated with lubrication and no further interventions, until complete resolution by 6 weeks. CONCLUSIONS AND IMPORTANCE: While the procedure of cosmetic blepharopigmentation is considered relatively safe, it bares many possible complications, ranging from mild dermal irritation to vision-threatening conditions. Our case of inadvertent keratopigmentation demonstrates the potential dangers of this procedure, and the importance of medical supervision and intervention in cases of complications. Vision preservation in this case was enabled by the midperipheral location of the pigment penetration.

Mitigation of Biofilm Formation on Corrugated Cardboard Fresh Produce Packaging Surfaces Using a Novel Thiazolidinedione Derivative Integrated in Acrylic Emulsion Polymers.

Various surfaces associated with the storage and packing of food are known to harbor distinct bacterial pathogens. Conspicuously absent among the plethora of studies implicating food packaging materials and machinery is the study of corrugated cardboard packaging, the worldwide medium for transporting fresh produce. In this study, we observed the microbial communities of three different store-bought fruits and vegetables, along with their analog cardboard packaging using high throughput sequencing technology. We further developed an anti-biofilm polymer meant to coat corrugated cardboard surfaces and mediate bacterial biofilm growth on said surfaces. Integration of a novel thiazolidinedione derivative into the acrylic emulsion polymers was assessed using Energy Dispersive X-ray Spectrometry (EDS) analysis and surface topography was visualized and quantified on corrugated cardboard surfaces. Biofilm growth was measured using q-PCR targeting the gene encoding 16s rRNA. Additionally, architectural structure of the biofilm was observed using SEM. The uniform integration of the thiazolidinedione derivative TZD-6 was confirmed, and it was determined via q-PCR to reduce biofilm growth by ~80% on tested surfaces. A novel and effective method for reducing microbial load and preventing contamination on food packaging is thereby proposed.

MRI segmentation analysis in temporal lobe and idiopathic generalized epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE) and idiopathic generalized epilepsy (IGE) patients have each been associated with extensive brain atrophy findings, yet to date there are no reports of head to head comparison of both patient groups. Our aim was to assess and compare between tissue-specific and structural brain atrophy findings in TLE to IGE patients and to healthy controls (HC). METHODS: TLE patients were classified in TLE lesional (L-TLE) or non-lesional (NL-TLE) based on presence or absence of MRI temporal structural abnormalities. High resolution 3 T MRI with automated segmentation by SIENAX and FIRST tools were performed in a group of patients with temporal lobe epilepsy (11 L-TLE and 15 NL-TLE) and in15 IGE as well as in 26 HC. Normal brain volume (NBV), normal grey matter volume (NGMV), normal white matter volume (NWMV), and volumes of subcortical deep grey matter structures were quantified. Using regression analyses, differences between the groups in both volume and left/right asymmetry were evaluated. Additionally, laterality of results was also evaluated to separately quantify ipsilateral and contralateral effects in the TLE group. RESULTS: All epilepsy groups had significantly lower NBV and NWMV compared to HC (p < 0.001). L-TLE had lower hippocampal volume than HC and IGE (p = 0.001), and all epilepsy groups had significantly lower amygdala volume than HC (p < = 0.004). In L-TLE, there was evidence of atrophy in both ipsilateral and contralateral structures. CONCLUSIONS: Our study revealed that TLE and IGE patients demonstrated similar overall tissue-specific brain atrophy, although specific structures differences were appreciated. L-TLE also appeared to behave differently than NL-TLE, with atrophy not limited to the ipsilateral side.

High-field pulsed EPR spectroscopy for the speciation of the reduced [PV(2)Mo(10)O(40)](6-) polyoxometalate catalyst used in electron-transfer oxidations.

An in-depth spectroscopic EPR investigation of a key intermediate, formally notated as [PV(IV)V(V)Mo(10)O(40)](6-) and formed in known electron-transfer and electron-transfer/oxygen-transfer reactions catalyzed by H(5)PV(2)Mo(10)O(40), has been carried out. Pulsed EPR spectroscopy have been utilized: specifically, W-band electron-electron double resonance (ELDOR)-detected NMR and two-dimensional (2D) hyperfine sub-level correlation (HYSCORE) measurements, which resolved (95)Mo and (17)O hyperfine interactions, and electron-nuclear double resonance (ENDOR), which gave the weak (51)V and (31)P interactions. In this way, two paramagnetic species related to [PV(IV)V(V)Mo(10)O(40)](6-) were identified. The first species (30-35 %) has a vanadyl (VO(2+))-like EPR spectrum and is not situated within the polyoxometalate cluster. Here the VO(2+) was suggested to be supported on the Keggin cluster and can be represented as an ion pair, [PV(V)Mo(10)O(39)](8-)[V(IV)O(2+)]. This species originates from the parent H(5)PV(2)Mo(10)O(40) in which the vanadium atoms are nearest neighbors and it is suggested that this isomer is more likely to be reactive in electron-transfer/oxygen-transfer reaction oxidation reactions. In the second (70-65 %) species, the V(IV) remains embedded within the polyoxometalate framework and originates from reduction of distal H(5)PV(2)Mo(10)O(40) isomers to yield an intact cluster, [PV(IV)V(V)Mo(10)O(40)](6-).

Oxidation of carbon monoxide cocatalyzed by palladium(0) and the H(5)PV(2)Mo(10)O(40) polyoxometalate probed by electron paramagnetic resonance and aerobic catalysis.

The H(5)PV(2)Mo(10)O(40) polyoxometalate and Pd/Al(2)O(3) were used as co-catalysts under anaerobic conditions for the activation and oxidation of CO to CO(2) by an electron transfer-oxygen transfer mechanism. Upon anaerobic reduction of H(5)PV(2)Mo(10)O(40) with CO in the presence of Pd(0) two paramagnetic species were observed and characterized by continuous wave electron paramagnetic resonance (CW-EPR) and hyperfine sublevel correlation (HYSCORE) spectroscopic measurements. Major species I (65-70%) is assigned to a species resembling a vanadyl cation that is supported on the polyoxometalate and showed a bonding interaction with (13)CO. Minor species II (30-35%) is attributed to a reduced species where the vanadium(IV) atom is incorporated in the polyoxometalate framework but slightly distanced from the phosphate core. Under aerobic conditions, CO/O(2), a nucleophilic oxidant was formed as elucidated by oxidation of thianthrene oxide as a probe substrate. Oxidation reactions performed on terminal alkenes such as 1-octene yielded a complicated mixture of products that was, however, clearly a result of alkene epoxidation followed by subsequent reactions of the intermediate epoxide. The significant competing reaction was a hydrocarbonylation reaction that yielded a approximately 1:1 mixture of linear/branched carboxylic acids.