Hyperpure chlorine dioxide versus chlorhexidine in intra-oral halitosis (ODOR trial) - protocol of a double-blinded, double-arm, parallel non-inferiority pilot randomized controlled trial.

INTRODUCTION: Intra-oral halitosis (IOH) is the most common type of bad breath; its consequences impair quality of life. However, evidence-based treatment protocols and guidelines are lacking. Our aim is to investigate the effectiveness of chlorine dioxide as an applicable complementary treatment modality in IOH after tongue cleaning. METHODS AND ANALYSIS: The ODOR trial will be a single-center, double-blinded, parallel-group, double-armed pilot randomized controlled trial with a non-inferiority design. The efficacy of hyperpure chlorine dioxide will be compared to chlorhexidine mouthwash. We plan to investigate the short-term effects of the intervention over a 3-h period. The primary endpoint will be changes in organoleptic test scores. At the end of the pilot investigation of the first 30 patients each, sample size calculation will be performed. If feasible, the investigators will continue the study by enrolling more patients. TRIAL REGISTRATION: The trial has been registered at ClinicalTrials.gov (NCT06219226).

The risk of developing splanchnic vein thrombosis in acute pancreatitis increases 3 days after symptom onset: A systematic review and meta-analysis.

BACKGROUND: Splanchnic vein thrombosis is a complication of acute pancreatitis (AP) and is likely often underdiagnosed. OBJECTIVES: We aimed to understand the time course and risk factors of splanchnic vein thrombosis in the early phase of AP. METHODS: A systematic search was conducted using the PRISMA guidelines (PROSPERO registration CRD42022367578). Inclusion criteria were appropriate imaging techniques in adult AP patients, studies that reported splanchnic vein thrombosis data from the early phase, and reliable information on the timing of imaging in relation to the onset of pancreatitis symptoms or hospital admission. The proportion of patients with thrombosis with 95% confidence intervals (CI) was calculated using random-effects meta-analyses, and multiple subgroup analyses were performed. RESULTS: Data from 1951 patients from 14 studies were analyzed. The proportion of patients with splanchnic vein thrombosis within 12 days after symptom onset was 0.13 (CI 0.07-0.23). The occurrence was lowest at 0.06 (CI 0.03-0.1) between 0 and 3 days after symptom onset, and increased fourfold to 0.23 (CI 0.16-0.31) between 3 and 11 days. On hospital admission, the proportion of patients affected was 0.12 (CI 0.02-0.49); it was 0.17 (CI 0.03-0.58) 1-5 days after admission. The prevalence in mild, moderate, and severe AP was 0.15 (CI 0.05-0.36), 0.26 (CI 0.15-0.43), and 0.27 (CI 0.17-0.4), respectively. Alcoholic etiology (0.31, CI 0.13-0.58) and pancreatic necrosis (0.55, CI 0.29-0.78, necrosis above 30%) correlated with increased SVT prevalence. CONCLUSION: The risk of developing splanchnic vein thrombosis is significant in the early stages of AP and may affect up to a quarter of patients. Alcoholic etiology, pancreatic necrosis, and severity may increase the prevalence of splanchnic vein thrombosis.

Persistently High Procalcitonin and C-Reactive Protein Are Good Predictors of Infection in Acute Necrotizing Pancreatitis: A Systematic Review and Meta-Analysis.

Infected necrotizing pancreatitis (INP) is associated with an increased risk of organ failure and mortality. Its early recognition and timely initiation of antibiotic therapy can save patients' lives. We systematically searched three databases on 27 October 2022. In the eligible studies, the presence of infection in necrotizing pancreatitis was confirmed via a reference test, which involved either the identification of gas within the necrotic collection through computed tomography imaging or the examination of collected samples, which yielded positive results in Gram staining or culture. Laboratory biomarkers compared between sterile necrotizing pancreatitis and INP were used as the index test, and our outcome measures included sensitivity, specificity, the receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Within the first 72 hours (h) after admission, the AUC of C-reactive protein (CRP) was 0.69 (confidence interval (CI): 0.62-0.76), for procalcitonin (PCT), it was 0.69 (CI: 0.60-0.78), and for white blood cell count, it was 0.61 (CI: 0.47-0.75). After the first 72 h, the pooled AUC of CRP showed an elevated level of 0.88 (CI: 0.75-1.00), and for PCT, it was 0.86 (CI: 0.60-1.11). The predictive value of CRP and PCT for infection is poor within 72 h after hospital admission but seems good after the first 72 h. Based on these results, infection is likely in case of persistently high CRP and PCT, and antibiotic initiation may be recommended.

Analysis of the ocular surface functional unit in episodic migraine.

AIM: Migraine is a chronic neurovascular disease that affects the trigeminovascular system. The purpose of this study was to evaluate corneal subbasal nerve fibers, dendritic cells and to measure tear film parameters in migraine. PATIENTS AND METHODS: 87 eyes of 44 patients suffering from migraine with a mean age of 33.23 ± 11.41 years were included in our study. 25 age-matched controls (mean age of 30.16 ± 12.59 years; P = 0.162) were recruited. The corneal subbasal plexus and the dendritic cells (DC) were analyzed using in vivo confocal microscopy (Heidelberg Retina Tomograph II Rostock Cornea Module; Heidelberg Engineering GmbH), and the tear film was imaged using LacryDiag (Quantel Medical, France). RESULTS: Regarding the subbasal nerve fibers of the cornea, none of the examined parameters differed significantly in migraine patients from controls. We found a significant increase in the corneal DC density (P < 0.0001) and DC area (P < 0.0001) in migraine patients compared to healthy volunteers. DC density showed a positive correlation with the monthly attack frequency (r = 0.32, P = 0.041) and the DC area a negative correlation with corneal nerve branch density (r = -0.233, P = 0.039), nerve fiber length (r = -0.232, P = 0.04) and total branch density (r = -0.233, P = 0.039). Using LacryDiag a significant loss of Meibomian gland area could be detected on the superior eyelid (P = 0.005) in migraine. CONCLUSIONS: Our results suggest the presence of neuroinflammation in the cornea of migraine patients affecting the peripheral trigeminal system. Dendritic cells surrounding the subbasal plexus may be involved in the activation and modulation of pain in migraine.

Fatty Pancreas Is a Risk Factor for Pancreatic Cancer: A Systematic Review and Meta-Analysis of 2956 Patients.

Pancreatic cancer (PC) is one of the most lethal cancers worldwide. Recently, fatty pancreas (FP) has been studied thoroughly, and although its relationship to PC is not fully understood, FP is suspected to contribute to the development of PC. We aimed to assess the association between PC and FP by conducting a systematic review and meta-analysis. We systematically searched three databases, MEDLINE, Embase, and CENTRAL, on 21 October 2022. Case-control and cross-sectional studies reporting on patients where the intra-pancreatic fat deposition was determined by modern radiology or histology were included. As main outcome parameters, FP in patients with and without PC and PC in patients with and without FP were measured. Proportion and odds ratio (OR) with a 95% confidence interval (CI) were used for effect size measure. PC among patients with FP was 32% (OR 1.32; 95% CI 0.42-4.16). However, the probability of having FP among patients with PC was more than six times higher (OR 6.13; 95% CI 2.61-14.42) than in patients without PC, whereas the proportion of FP among patients with PC was 0.62 (95% CI 0.42-0.79). Patients identified with FP are at risk of developing PC. Proper screening and follow-up of patients with FP may be recommended.

ORGANOLEPTIC AND HALITOMETRIC ASSESSMENTS DO NOT CORRELATE WELL IN INTRA-ORAL HALITOSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: The gold standard method for diagnosing oral halitosis is the subjective organoleptic measurement. Device-supported methods are also widespread worldwide. The challenges and safety concerns around performing organoleptic measurements during pandemics and the diversity of measuring device alternatives raised our clinical question: which halitometer is the most suitable for diagnosing halitosis? METHODS: This systematic review was registered in PROSPERO (ID CRD42022320024). The search was performed on March 23, 2022 in the following electronic databases: MEDLINE, Embase, Scopus, Web of Science, and CENTRAL. Adult populations with or without halitosis were included, and patients with systemic diseases were excluded. Organoleptic (subjective) measurement and the device-supported (objective) methods were compared; the primary outcome was the correlation coefficient, and the secondary was the specificity and sensitivity of the devices. QUADAS-2 and QUADAS-C were used to evaluate the risk of bias in the studies. Random-effects meta analyses were performed on the outcomes, and the secondary outcomes were plotted on a common ROC plot. RESULTS: A total of 1231 records were found in the 5 databases. After the selection process, 76 articles were eligible for the systematic review, and 14,635 patients were involved in the qualitative analysis. The pooled Spearman's correlation coefficient (c.c.) for sulfide monitors was 0.65; 95% CIs: [0.53-0.74]; I2 = 95%, P < .01. The pooled Spearman's c.c. for portable gas chromatographs was 0.69; 95% CIs: [0.63-0.74]; I2 = 12%, P < .01. The pooled Spearman's c.c. for gas chromatographs was 0.76; 95% CIs: [0.67-0.83]; I2 = 0%, P < .01. DISCUSSION: None of the most commonly used halitometers proved to be significantly superior to the others. Halimeter and OralChroma measurements did not correlate well with the organoleptic level of oral halitosis in adults. Therefore, better halitometers need to be developed as an alternative to organoleptic measurements.

The use of autogenous tooth bone graft is an efficient method of alveolar ridge preservation - meta-analysis and systematic review.

BACKGROUND: Ridge resorption following tooth extraction may be reduced by alveolar ridge preservation (ARP). Previous randomized clinical trials and systematic reviews have suggested that autogenous tooth bone graft (ATB) can be an effective alternative material for ARP. However, the results are heterogeneous. Therefore, our research aimed to evaluate the efficacy of ATB in ARP. METHODS: A systematic search was conducted in Cochrane Library, Embase, MEDLINE and Scopus for studies published from inception to 31 November 2021. We searched searched for randomized, non-randomized controlled trials and case series reporting on ATB use for ARP. The primary outcome was the ridge width difference pre- and post-surgery, measured in millimetres (mm) measured on CBCT (cone beam computed tomography). The secondary outcomes were the histological results. We followed the PRISMA2020 recommendations for reporting our systematic review and meta-analysis. RESULTS: The analysis included eight studies for the primary and six for the secondary outcomes. The meta-analysis revealed a positive ridge preservation effect with a pooled mean difference ridge width change of -0.72 mm. The pooled mean residual graft proportion was 11.61%, and the newly formed bone proportion was 40.23%. The pooled mean of newly formed bone proportion was higher in the group where ATB originated from both the root and crown of the tooth. CONCLUSIONS: ATB is an effective particulate graft material in ARP. Complete demineralization of the ATB tends to decrease the proportion of newly formed bone. ATB can be an attractive option for ARP. TRIAL REGISTRATION: The study protocol was registered on PROSPERO (CRD42021287890).

Pre-Ophthalmoscopic Quantitative Biomarkers in Diabetes Mellitus.

Purpose: The purpose of this study was to assess whether retinal microvascular or corneal nerve abnormalities occur earlier in diabetes mellitus (DM) and to identify imaging biomarkers in order to help prevent the subsequent irreversible retinal and corneal complications. Methods: The study comprised 35 eyes of 35 healthy volunteers and 52 eyes of 52 patients with type 1 and type 2 DM. Swept-source optical coherence tomography (OCT), OCT angiography, and in vivo corneal confocal microscopy were performed in both groups. Corneal sub-basal nerve plexus and vessel density (VD) of superficial capillary plexus (SCP) and deep capillary plexus (DCP) were evaluated. Results: All corneal sub-basal nerve fiber parameters were decreased in patients with DM compared with healthy subjects and the difference was significant for each result except for nerve fiber width (P = 0.586). No significant correlation was obtained between any nerve fiber morphology parameters and disease duration or HbA1C. VD in SCP was significantly decreased in the superior (P < 0.0001), temporal (P = 0.001), and nasal quadrant (P = 0.003) in the diabetes group. In DCP, only superior VD (P = 0.036), decreased significantly in the diabetes group. Ganglion cell layer thickness in the inner ring showed a significantly lower value in patients with DM (P < 0.0001). Conclusions: Our results implicate a more pronounced and earlier damage to the corneal nerve fibers compared to the retinal microvasculature in patients with DM. Translational Relevance: In DM, an earlier and more pronounced damage to the corneal nerve fibers was observed compared to the retinal microvasculature.

Ocular Manifestations of Hurler-Scheie Syndrome: Recurrence of Host Disease in the Corneal Transplant.

Introduction: Hurler-Scheie syndrome is a type of mucopolysaccharidosis I (MPS). In MPS I the decreased activity of alpha-L-iduronidase lysosomal enzyme leads to glycosaminoglycan (GAG) deposition in the intra- and extracellular matrix. Excessive amounts of GAG can accumulate in most layers of the cornea, including epithelial cells, stromal keratocytes, and endothelial cells. Case Presentation: A 25-year-old female patient suffering from Hurler-Scheie syndrome with multiple ocular manifestations is reported. Due to significant bilateral corneal opacification, penetrating keratoplasty was performed on both eyes. Histopathologic examination of the corneal buttons showed disorganized collagen fibers with heterogenous thickness and many granule-containing keratocytes with excessive cytoplasm. Despite receiving enzyme replacement therapy, in vivo confocal microscopy revealed characteristic vacuoles in the basal epithelium and corneal stroma 96 months after transplantation. High resolution anterior segment optical coherence tomography demonstrated hyperreflective opacities superficial and deeper in the stroma which was consistent with recurrence of host disease in the graft. Conclusion: To the best of our knowledge, this is the first documented Hurler-Scheie syndrome case of recurrence after penetrating keratoplasty demonstrated by in vivo confocal microscopy. Additionally, this patient manifested severe ocular involvement of MPS which might be an explanation of the progressive course of corneal opacification after transplantation.

Daily use of chlorine dioxide effectively treats halitosis: A meta-analysis of randomised controlled trials.

OBJECTIVES: We aimed to conduct a systematic review on published data in order to investigate the efficacy of mouthwash products containing chlorine dioxide in halitosis. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Our search was conducted on 14th October 2021. We searched the following electronic databases: MEDLINE, Embase, Scopus, Web of Science, and CENTRAL. We analysed data on adults with halitosis, included only randomised controlled trials and excluded in vitro and animal studies. The interventional groups used chlorine dioxide, and the comparator groups used a placebo or other mouthwash. Our primary outcomes were changes in organoleptic test scores (OLS) and Volatile Sulfur Compound (VSC) levels from baseline to the last available follow-up. RESULTS: We found 325 articles in databases. After the selection process, ten articles were eligible for qualitative synthesis, and 7 RCTs with 234 patients were involved in the meta-analysis. Our findings showed a significant improvement in the parameters of the chlorine dioxide group compared to the placebo group in OLS one-day data (mean difference (MD): -0.82; 95% confidence intervals (95% CIs): [-1.04 --0.6]; heterogeneity: I2 = 0%, p = 0.67); and one-week OLS data (MD: -0.24; 95% CIs: [-0.41 --0.07]; I2 = 0%, p = 0.52); and also changes in H2S one-day data (standardised mean difference (SMD): -1.81; 95% CIs: [-2.52 --1.10]); I2 = 73.4%, p = 0.02). CONCLUSION: Our data indicate that chlorine dioxide mouthwash may be a good supportive therapy in oral halitosis without known side effects.

Addition of epidermal growth factor receptor inhibitors to standard chemotherapy increases survival of advanced head and neck squamous cell carcinoma patients: A systematic review and meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) is among the common tumors associated with high mortality. The aim of our meta-analysis was to determine how additional anti-epidermal growth factor receptor (EGFR) therapy to standard chemotherapy affects the progression-free (PFS) and overall survival (OS) of the patients, besides the most common side effects. We used CENTRAL, MEDLINE, and Embase databases until October 26, 2020, and included 13 eligible randomized controlled trials in our systematic research. The pooled hazard ratios (HR) for the main outcomes from the original data were estimated and for the other dichotomous outcomes, odds ratios (ORs) with their 95% confidence intervals (CI) were calculated. Addition of EGFR inhibitors to conventional chemotherapy significantly decreased the death and disease progression (for PFS HR: 0.68, 95% CI: 0.55-0.81, I2  = 65.5%, p = 0.005) and mortality (for OS HR: 0.83, 95% CI: 0.72-0.94, I2  = 42.3%, p = 0.076). In the EGFR inhibitor group, we revealed an increased chance of the over Grade 3 skin rashes (OR: 4.86; 95% CI: 1.52-15.49, I2  = 2.3%, p = 0.407), and all Grade skin rashes (OR: 18.32, 95% CI: 8.07-41.60, I2  = 56.6%, p = 0.032). Despite their unwanted dermatological side effects, the addition of EGFR inhibitors is recommended to be included in advanced HNSCC therapy.

Topical pharmacotherapy for ocular surface squamous neoplasia: systematic review and meta-analysis.

Ocular surface squamous neoplasia (OSSN) has different treatment modalities. Although surgical excision has been the gold standard therapeutic option, topical pharmacotherapy agents such as 5-fluorouracil (5-FU), interferon alfa-2b (IFN) and mitomycin-C (MMC) are also commonly used. The protocol was registered (CRD42021224961). Comprehensive literature research was carried out to compare topical pharmacotherapy (5-FU or IFN or MMC) to surgical excision regarding clinical success (tumor resolution), recurrence and complications in patients undergoing treatment for OSSN. From 7859 records, 7 articles were included in the qualitative and 4 in the quantitative synthesis. The outcomes of surgical excision and topical pharmacotherapy were comparable in the included articles. There were no significant differences between surgical excision and topical pharmacotherapy regarding the clinical success [odds ratio (OR): 0.785; confidence interval (CI): 0.130-4.736, P = 0.792)] and tumor recurrence (OR: 0.746; CI: 0.213-2.609; P = 0.646). The most common side effect of the different therapeutic options was dry eye. The highest rate of dry eye symptoms was reported after surgical excision (in 59%). Topical pharmacotherapy with all the 3 agents is as effective and well-tolerable as surgical excision in terms of tumor resolution, recurrence rate and side effects in all OSSN patients suggesting similar long-term clinical benefits.

Corneal Cellular and Neuroinflammatory Changes After SARS-CoV-2 Infection.

PURPOSE: The purpose of this study was to evaluate corneal cellular and ultrastructural changes and to quantify the neuroinflammatory process in patients after mild severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Thirty patients after SARS-CoV-2 infection and 41 age-matched controls were examined. All subjects underwent in vivo confocal microscopy of the corneal cell layers and subbasal nerve fibers with the Heidelberg Retina Tomograph II. Semiautomated analysis of basal epithelial, anterior and posterior stromal keratocyte, and endothelial cell density was performed. Dendritic cell (DC) density and area were also calculated, and subbasal nerve plexus morphology was analyzed. RESULTS: The posterior stromal keratocyte density was significantly lower in patients after SARS-CoV-2 infection ( P = 0.0006). DC density in the central cornea was significantly higher in patients after SARS-CoV-2 infection ( P = 0.0004). There was a significant difference in the DC area between the 2 groups ( P < 0.0001). Significantly altered subbasal nerve fiber morphology was detected in patients after SARS-CoV-2 infection compared with healthy volunteers ( P < 0.05). CONCLUSIONS: Corneal cellular and ultrastructural changes demonstrated in this study suggest neuroinflammatory consequences of COVID-19 in the cornea in the absence of ophthalmoscopic alterations.

Analysis of microvascular and neurodegenerative complications of mild COVID-19.

PURPOSE: To examine retinal and corneal neurodegenerative and retinal microvascular changes in patients after mild or asymptomatic COVID-19 disease compared to age-matched controls. METHODS: Thirty-five (35) patients after PCR-proven SARS-CoV-2 infection and 28 age-matched controls were enrolled. Swept-source optical coherence tomography (OCT), OCT angiography, and in vivo corneal confocal microscopy were performed in both groups. Corneal subbasal nerve plexus was quantified. Vessel density for superficial (SCP) and deep capillary plexus (DCP) and structural OCT parameters were recorded. RESULTS: Significantly lower nerve branch density (P = 0.0004), nerve fiber area (P = 0.0001), nerve fiber density (P = 0.0009), nerve fiber length (P < 0.0001), and total nerve branch density (P = 0.002) values were observed in patients after COVID-19 compared to healthy controls. VD of the temporal SCP was significantly different between the two groups (P = 0.019). No other SCP and DCP vessel density parameter differed significantly between the two groups. CONCLUSIONS: Our results suggest that peripheral neurodegenerative changes may occur even after mild or asymptomatic SARS-CoV-2 infection. No relevant microvascular changes were seen with OCT angiography and structural OCT parameters did not show any signs of optic neuropathy in post-COVID patients. In vivo confocal microscopy seems to be an important tool in monitoring peripheral neuropathy in patients after COVID-19.

Comparative analysis of two optical biometry devices: high wavelength swept source OCT versus partial coherence interferometry.

PURPOSE: To study the reproducibility of measurements performed with a recently developed multimodal high resolution swept source optical coherence tomography (SSOCT) and to make comparisons with a partial coherence interferometry (PCI) biometer. METHODS: One hundred and fifty-two eyes of 152 subjects were involved in this study with a mean age of 65.71 ± 13.86 years (26-85 years). Anterior surface keratometry (K), anterior chamber depth (ACD), white-to-white (WTW) and axial length (AL) values were recorded by the SSOCT (ANTERION, Heidelberg Engineering Ltd, Germany) and PCI (IOLMaster 500, version 5.5, Carl Zeiss Meditec, Germany). Intraocular lens (IOL) power was calculated based on ANTERION and IOLMaster keratometry values by using five traditional vergence formulas. RESULTS: Anterior surface simulated keratometry values did not differ significantly between the IOLMaster and ANTERION (P > 0.05). AL measurements were successful in 95% of the cases both with the SSOCT and PCI. No significant difference was disclosed between the two instruments (P = 0.229). For WTW measurements, a significant difference was observed between the two optical biometers (P < 0.0001). The difference between PCI and SSOCT in IOL powers was statistically significant for SRK/T, Hoffer and Holladay formulas (P < 0.001). CONCLUSION: Our results implicated an overall good reproducibility of anterior keratometry, AL, ACD and WTW measurements for IOLMaster and ANTERION. The discrepancies between their measurements resulted in significant difference in the calculated IOL power for SRK/T, Hoffer and Holladay formulas, but not for Haigis formula.

Acute central retinal artery occlusion: Proposed therapeutic approach for ocular stroke / Akut arteria centralis retinae elzáródás; Az ocularis stroke induló terápiás programja

Összefoglaló. Az agy és a szem vascularis katasztrófái számos esetben egymáshoz társuló vagy egymást elore jelzo kórképek. Az arteria centralis retinae occlusio az ér rekanalizációjának hiányában a retina szöveteinek irreverzibilis károsodását okozza. Sem a nemzetközi, sem a hazai stroke-irányelvek nem foglalkoznak az ocularis stroke problémakörével, annak ellenére, hogy az arteria centralis retinae occlusio okozta retinalis ischaemia minden tekintetben megfelel az akut ischaemiás stroke definíciójának. Az eddig rendelkezésre álló irodalmi adatok alapján arteria centralis retinae occlusio esetén az intravénás thrombolysis 4,5 órán belül alkalmazva növeli a szignifikáns mértéku visusjavulás esélyét. Az országban jelenleg 4 centrum (Pécsi Tudományegyetem, Szegedi Tudományegyetem, Debreceni Egyetem, Semmelweis Egyetem) tervezi az ocularis stroke kezelésében a thrombolysis bevezetését. A maradandó látásromlás és a szekunder cerebrovascularis események megelozése érdekében elengedhetetlen az alapellátásban és a társszakmákban dolgozó kollégákkal való szoros együttmuködés. Orv Hetil. 2021; 162(47): 1871-1875. Summary. Vascular events of the brain and the eye may occur concomitantly or sequentially. In the absence of recanalization, central retinal artery occlusion causes irreversible damage to the retinal tissues. Even though retinal ischemia secondary to central retinal artery occlusion meets the definition of acute ischemic stroke, neither the international nor the Hungarian stroke guidelines mention ocular stroke. Based on the available literature, intravenous thrombolysis of the central retinal artery within 4.5 hours of occlusion can increase the odds of significant vision improvement. Currently 4 centers (University of Pécs, Debrecen, Szeged, and Semmelweis University) are planning to introduce thrombolysis in the treatment of ocular stroke. To prevent permanent visual loss and secondary cerebrovascular events, timely intervention requires the collaboration between general practitioners and other specialties. Orv Hetil. 2021; 162(47): 1871-1875.

An in vivo confocal microscopy study of corneal changes in patients with systemic sclerosis.

To investigate corneal microstructure of systemic sclerosis (SSc) patients using in vivo confocal microscopy (IVCM). 33 patients with SSc and 30 age-matched healthy subjects were recruited. All participants underwent comprehensive ophthalmic examination including IVCM (Heidelberg Retina Tomograph III, Heidelberg Engineering GmbH, Heidelberg, Germany) and ocular surface evaluation. Subbasal nerve plexus morphology was investigated using automated software analysis (ACCMetrics V3; University of Manchester, Manchester, UK). Keratocyte cell densities in the anterior stroma were significantly lower in patients with SSc compared to controls (P < 0.0001). In 7 SSc patients no keratocyte nuclei were identified in the anterior stroma and in most patients scattered hyperreflective punctate material were observed in the anterior stroma. Significantly lower subbasal nerve fiber parameters were found in patients with SSc compared to healthy subjects (P < 0.05). There were no significant correlations between the duration of SSc and any of the corneal cell density values. Tear break-up time values (4.82 ± 3.15 s) and Ocular Surface Disease Index scores (33.27 ± 30.11) were abnormal, Schirmer values (6.78 ± 5.82 mm) were borderline in SSc patients. In SSc, corneal morphological changes and accumulation of punctate material in the stroma was detected with confocal microscopy. Severe ocular surface disease was observed in SSc patients with significant impairment in subbasal nerve plexus morphology resembling peripheral neuropathy.

Estimation of the timing of BAP1 mutation in uveal melanoma progression.

Uveal melanoma is the most common primary intraocular malignancy. A vast majority of metastasizing tumors have mutations in the BAP1 gene. Here, we investigate the spatiotemporal timing of these mutations. The size of 177 uveal melanomas and 8.3 million individual tumor cells was measured. BAP1 sequencing results and BAP1 IHC were available and for 76 (43%) and 101 (57%) of these, respectively. Tumors with a BAP1 mutation had significantly larger volume (2109 vs. 1552 mm3, p = 0.025). Similarly, tumor cells with loss of BAP1 protein expression had significantly larger volume (2657 vs. 1593 µm3, p = 0.027). Using observations of the time elapsed between mitoses, the BAP1 mutation was calculated to occur when the primary tumor had a size of a few malignant cells to 6 mm3, 0.5 to 4.6 years after tumor initiation and at least 9 years before diagnosis. We conclude that BAP1 mutations occur early in the growth of uveal melanoma, well before the average tumor is diagnosed. Its timing coincides with the seeding of micrometastases.