Search Results (6)

Background: Immune checkpoint inhibitors (ICIs) can induce a sicca-like syndrome that differs from primary Sjögren’s disease in both immunopathogenesis and clinical phenotype. Despite growing recognition of this entity, data describing real-world management and outcomes, particularly in the context of ICI discontinuation and rechallenge, remain limited. Methods: Patients with new onset of sicca syndrome or exacerbation of previous symptoms following ICI therapy were retrospectively identified and assessed. Results: Fifty-nine patients with diverse malignancies (including melanoma, gastrointestinal, genitourinary, etc.) and sicca syndrome following treatment with ICIs (most often pembrolizumab or nivolumab +/− ipilimumab) were evaluated. Acute-onset dry mouth, primarily CTCAE v6.0 grades 1 (n = 24, 40.7%) and 2 (n = 34, 57.6%), occurred at a median of 104 days after ICI initiation, sometimes with associated dry eye (n = 8, 13.6%). Most were managed conservatively with behavioral modification and over-the-counter therapies alone (n = 37, 62.7%) while others received sialagogues (n = 9, 15.3%), dexamethasone oral rinse (n = 11, 18.6%), and/or systemic corticosteroids (n = 16, 27.1%). Additional management strategies included de-escalation to ICI monotherapy (n = 5, 8.5%) or discontinued ICI (n = 6, 10.2%). Half of patients treated with corticosteroids demonstrated subjective improvement in symptoms while 75% improved following ICI discontinuation. Four patients underwent rechallenge after a median interruption of 564 days; all (n = 4) demonstrated sicca recurrence. Conclusions: In this largest cohort to date of ICI-associated sicca syndrome, we confirm frequent improvement with steroids and/or supportive care and suggest a greater than previously appreciated risk of recurrence with rechallenge. Full article

Background: Scattering of the sclera limits optical coherence tomography (OCT) imaging of deeper targets including lesions, malignancies, and other surgical targets. While existing applications of fluorescein dye are currently focused on fluorescence properties for tissue labeling, the absorption characteristics of the dye also hold potential for scleral tissue clearing. Methods: Fluorescein is investigated here to gauge the potential impact of its optical clearing on intrasurgical OCT guidance. Fluorescein was applied topically to ex vivo porcine and human eye models. OCT imaging was conducted over time to assess the increases in imaging depth due to fluorescein clearing. High-speed microscope-integrated OCT was used during pilot trabeculectomy surgery on cleared eye models to assess clearing applications in a surgical context. Results: The OCT depth of imaging increased with fluorescein concentration and application time. The effect saturates at a near-20% concentration with 50 min of application time, with a maximum signal increase of +15 dB. Reversal of the effect was observed following 10 min of rinsing. Conclusions: High-concentration fluorescein dye has novel applications as an optical clearing agent, increasing the OCT imaging depth through highly scattering biological tissue. These properties can be leveraged for improved image guidance in surgical contexts. Full article

Background: Sudden volcanic eruptions can lead to volcanic ash entering the eyes, causing severe discomfort and complicating evacuation efforts. The specific effects of volcanic ash on ocular tissues, especially when wearing soft contact lenses (SCLs), are not well documented, prompting this experimental investigation. Methods: White rabbits with normal eyes were randomly divided into three groups: (1) a bare eye group: bare eye + volcanic ash exposure + eye washing, (2) an SCL group: SCL-wearing eye + volcanic ash exposure + eye washing, and (3) a control group: eye washing only. In groups 1 and 2, volcanic ash was applied to one eye under topical anesthesia, followed by immediate saline rinsing. Slit-lamp microscopy and histopathological analysis were conducted after euthanasia. Results: Slit-lamp and histopathological examinations revealed more significant corneal and conjunctival erosion in the bare eye group compared to the SCL group, which showed limited damage. The control group displayed no ocular damage. Conclusions: Guidelines from the “Volcanic Ash Health Effects: A Guide for the Public” by the National Research Institute for Earth Science and Disaster Resilience recommend removing SCLs during ashfall. Our findings suggest that the damage to the corneal and conjunctival epithelium is less severe in SCL-wearing eyes than in bare eyes, recommending that SCL wearers prioritize evacuation over lens removal during sudden ashfall. Full article

Purpose: Chemical eye injury is an acute emergency that can result in vision loss. Neurotrophic keratitis (NK) is the most common long-term manifestation of chemical injury. NK due to alkali burn affects ocular surface health and is one of its most common causes. Here, we established a rabbit model of corneal alkali burns to evaluate the severity of NK-associated changes. Material methods: Alkali burns were induced in NZ rabbits by treating the cornea with (i) a 5 mm circular filter paper soaked in 0.75 N NaOH for 10 s (Mild NK) and (ii) trephination using a guarded trephine (5 mm diameter and 150-micron depth), followed by alkali burn, with a 5 mm circular filter paper soaked in 0.75 N NaOH for 10 s (a severe form of NK). Immediately after, the cornea was rinsed with 10 mL of normal saline to remove traces of NaOH. Clinical features were evaluated on Day 0, Day 1, Day 7, Day 15, and Day 21 post-alkali burn using a slit lamp, Pentacam, and anterior segment optical coherence tomography (AS-OCT). NK-like changes in epithelium, sub-basal nerve plexus, and stroma were observed using in vivo confocal microscopy (IVCM), and corneal sensation were measured using an aesthesiometer post alkali injury. After 21 days, pro-inflammatory cytokines were evaluated for inflammation through ELISA. Results: Trephination followed by alkali burn resulted in the loss of epithelial layers (manifested using fluorescein stain), extensive edema, and increased corneal thickness (550 µm compared to 380 µm thickness of control) evaluated through AS-OCT and increased opacity score in alkali-treated rabbit (80 compared to 16 controls). IVCM images showed complete loss of nerve fibers, which failed to regenerate over 30 days, and loss of corneal sensation—conditions associated with NK. Cytokines evaluation of IL6, VEGF, and MMP9 indicated an increased angiogenic and pro-inflammatory milieu compared to the milder form of NK and the control. Discussion: Using clinical parameters, we demonstrated that the alkali-treated rabbit model depicts features of NK. Using IVCM in the NaOH burn animal model, we demonstrated a complete loss of nerve fibers with poor self-healing capability associated with sub-basal nerve degeneration and compromised corneal sensation. This pre-clinical rabbit model has implications for future pre-clinical research in neurotrophic keratitis. Full article

This study aimed to (1) determine whether the expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 is increased in tobacco smokers, which potentially increases their susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and (2) assess whether eye rinsing can reduce susceptibility. This prospective study included 20 eyes of 10 smokers and 18 eyes of nine healthy non-smokers (control) for reverse-transcription polymerase chain reaction. This study also included 28 eyes of 14 smokers and 16 eyes of eight healthy non-smokers (control) for enzyme-linked immunosorbent assay. Tear and impression cytology samples were collected from the right eye of each patient. The left eye was then rinsed for 30 s, and after 5 min, the tear and impression cytology samples were collected in the same manner. The expression of the ACE2 gene was significantly higher in the conjunctiva of smokers (n = 17; median 3.07 copies/ng of total RNA) than in those of non-smokers (n = 17; median 1.92 copies/ng of total RNA, p = 0.003). Further, mRNA expression and protein levels of ACE2 were weakly correlated in smokers (r = 0.49). ACE2 protein levels in Schirmer’s strip samples were significantly reduced from 5051 to 3202 pg/mL after eye washing (n = 10; p = 0.001). Ocular surface cells are susceptible to SARS-CoV-2 infection. Smoking may be a risk factor for SARS-CoV-2 infection, and eye rinsing may reduce the risk of infection. Full article

Discolouration resulting from regenerative endodontic procedures may have a negative impact on the quality of life of treated patients; therefore, it is recommended to minimize this risk by selecting appropriate scaffolds and barrier materials, and if discolouration occurs, the use of a simple, cost-effective and minimally invasive technique, such as whitening, should be considered. This in vitro study aimed to evaluate tooth discolouration after two- and single-visit regenerative endodontic procedures and the effectiveness of subsequent whitening procedures with carbamide peroxide. Two hundred bovine incisors were included in this study and divided into twenty groups based on the tested material combinations. Two groups were control groups, one with saline and the other group with blood. In the 12 groups, the experiment was designed to be consistent with the two-visit regenerative endodontic procedures. Triple antibiotic paste or calcium hydroxide were placed in the root canal, and then scaffolds (e.g., blood or platelet-rich fibrin) and barrier materials (Biodentine, OrthoMTA or MTA Repair HP) were applied after rinsing the disinfectant pastes. In the six groups that corresponded to the single-visit regenerative endodontic procedure, the use of a disinfectant paste was omitted. Subsequently, the specimens were bleached twice with carbamide peroxide at a 7-day interval. Colour change measurements were performed using a spectrophotometer (VITA Easyshade Compact 5.0, VITA Zahnfabrik, Bad Säckingen, Germany). Statistical analysis was performed with the Kruskal–Wallis H test, the independent t-test and t-test for related samples. Tooth discolouration was noticed after two- and single-visit regenerative endodontic procedures, except for the platelet-rich fibrin+MTA Repair HP group. After the first and second whitening procedures, all of the tested two- and single-visit regenerative endodontic procedures groups showed a change in the colour of the crown, which was noticeable to the naked eye (∆E > 3.3). When analysing the ∆E value between the first and second bleaching procedures, no changes in the colour of teeth were visually noticed in the calcium hydroxide and platelet-rich fibrin +MTA Repair HP groups (∆E < 3.3). Single-visit regenerative endodontic procedures are suggested if possible; however, if two-visit regenerative endodontic procedures are performed, it is recommended to use calcium hydroxide as the disinfectant paste because of the lower staining potential. In the context of discolouration, platelet-rich fibrin is advisable for use as a scaffold. The whitening procedure is worth considering, but does not guarantee a return to the original tooth colour, especially when triple antibiotic paste is used. Full article