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Background Idiopathic intracranial hypertension (IIH) is a syndrome exhibiting elevated intracranial pressure (ICP), visual disturbances, and severe headache. IIH primarily affects young obese women, though it can occur in individuals of any age, BMI, and sex. IIH is characterized by systemic metabolic dysregulation with a profile of increased androgen hormones. However, the contribution of obesity/hormonal perturbations to cerebrospinal fluid (CSF) dynamics remains unresolved.Methods We employed obese female Zucker rats and adjuvant testosterone to reveal IIH causal drivers. ICP and CSF dynamics were determined with in vivo experimentation and magnetic resonance imaging, testosterone levels assessed with mass spectrometry, and choroid plexus function revealed with transcriptomics. Results Obese rats had undisturbed CSF testosterone levels and no changes in ICP or CSF dynamics. Adjuvant testosterone treatment of obese rats elevated the CSF secretion rate, although with no effect on the ICP, due to elevated CSF drainage capacity of these rats. Conclusions Obesity in itself therefore does not suffice to recapitulate the IIH symptoms in rats, but modulation of CSF dynamics appears with adjuvant testosterone treatment, which mimics the androgen excess observed in female IIH patients. Obesity-induced androgen dysregulation may thus contribute to the disease mechanism of IIH and could potentially serve as a future therapeutic target.

Purpose: To investigate the cell survival of human conjunctival goblet cells (CGs) when incubated with preserved and preservative-free (PF) artificial tears (AT) used against dry eye disease (DED). The following ATs were tested: 0.011% benzalkonium chloride (BAK)-preserved Viskøse Øjendråber, 0.006% BAK-preserved Oftagel, 0.005% BAK-preserved Oculac, 0.001% PolyQuad-preserved Systane Ultra, 0.01% Cetrimide-preserved Artelac, and PF ATs: Systane Ultra, Oculac, Oftagel, and Thealoz Duo. Method: Primary cultures of human conjunctival CGs were cultivated from donor conjunctiva. After incubation with said ATs for 2 hours, CG survival was analysed using a lactate dehydrogenase assay and calculated to a negative control. Results: AT preserved with 0.011% BAK reduced GC survival by 28% compared to negative control (p=0.001). The remaining ATs did not significantly alter the cell survival. Conclusion: BAK-preserved ATs cause GC death in a concentration-dependent manner. Reduction of the GC density may contribute to the development of DED. PF-ATs and PolyQuad- and Cetrimide-preserved ATs may thus be a better choice for treating DED than BAK-preserved ATs, as the latter may add to ocular surface disease., Aims/Purpose: To investigate the cell survival of human conjunctival goblet cells (CGs) when incubated with preserved and preservative-free (PF) artificial tears (AT) used against dry eye disease (DED). The following ATs were tested: 0.011% benzalkonium chloride (BAK)-preserved Viskøse® Øjendråber, 0.006% BAK-preserved Oftagel®, 0.005% BAK-preserved Oculac®, 0.001% PolyQuad™-preserved Systane® Ultra, 0.01% Cetrimide-preserved Artelac®, and PF ATs: Systane® Ultra, Oculac®, Oftagel®, and Thealoz® Duo. Methods: Primary cultures of human conjunctival CGs were cultivated from donor conjunctiva. After incubation with the above-mentioned ATs for 2 h, CG survival was analysed using a lactate dehydrogenase assay and calculated to a negative control. Results: AT preserved with 0.011% BAK reduced GC survival by 28% compared to negative control (p = 0.001). The remaining ATs did not significantly alter the cell survival. Conclusions: BAK-preserved ATs cause GC death in a concentration-dependent manner. Reduction of the GC density may contribute to development of DED. PF-ATs and PolyQuad- and Cetrimide-preserved ATs may thus be a better choice for treating DED than BAK preserved ATs, as the latter may add to the ocular surface disease.

Background Skin tape-strips and biopsies are widely used methods for investigating the skin in atopic dermatitis (AD). Biopsies are more commonly used but can cause scarring and pain, whereas tape-strips are noninvasive but sample less tissue. The study evaluated the performance of skin tape-strips and biopsies for studying AD. Methods Whole-transcriptome RNA-sequencing was performed on paired tape-strips and biopsies collected from lesional and non-lesional skin from AD patients (n = 7) and non-AD controls (n = 5). RNA yield, mapping efficiency, and differentially expressed genes (DEGs) for the two methods (tape-strip/biopsy) and presence of AD (AD/non-AD) were compared. Results Tape-strips demonstrated a lower RNA yield (22 vs. 4596 ng) and mapping efficiency to known genes (28% vs. 93%) than biopsies. Gene-expression profiles of paired tape-strips and biopsies demonstrated a medium correlation (R2 = 0.431). Tape-strips and biopsies demonstrated systematic differences in measured expression levels of 6483 genes across both AD and non-AD samples. Tape-strips preferentially detected many itch (CCL3/CCL4/OSM) and immune-response (CXCL8/IL4/IL5/IL22) genes as well as markers of epidermal dendritic cells (CD1a/CD207), while certain cytokines (IL18/IL37), skin-barrier genes (KRT2/FLG2), and dermal fibroblasts markers (COL1A/COL3A) were preferentially detected by biopsies. Tape-strips identified more DEGs between AD and non-AD (3157 DEGs) then biopsies (44 DEGs). Tape-strips also detected higher levels of bacterial mRNA than biopsies. Conclusions This study concludes that tape-strips and biopsies each demonstrate respective advantages for measuring gene-expression changes in AD. Thus, the specific skin layers and genes of interest should be considered before selecting either method., Background: Skin tape-strips and biopsies are widely used methods for investigating the skin in atopic dermatitis (AD). Biopsies are more commonly used but can cause scarring and pain, whereas tape-strips are noninvasive but sample less tissue. The study evaluated the performance of skin tape-strips and biopsies for studying AD. Methods: Whole-transcriptome RNA-sequencing was performed on paired tape-strips and biopsies collected from lesional and non-lesional skin from AD patients (n = 7) and non-AD controls (n = 5). RNA yield, mapping efficiency, and differentially expressed genes (DEGs) for the two methods (tape-strip/biopsy) and presence of AD (AD/non-AD) were compared. Results: Tape-strips demonstrated a lower RNA yield (22 vs. 4596 ng) and mapping efficiency to known genes (28% vs. 93%) than biopsies. Gene-expression profiles of paired tape-strips and biopsies demonstrated a medium correlation (R2 = 0.431). Tape-strips and biopsies demonstrated systematic differences in measured expression levels of 6483 genes across both AD and non-AD samples. Tape-strips preferentially detected many itch (CCL3/CCL4/OSM) and immune-response (CXCL8/IL4/IL5/IL22) genes as well as markers of epidermal dendritic cells (CD1a/CD207), while certain cytokines (IL18/IL37), skin-barrier genes (KRT2/FLG2), and dermal fibroblasts markers (COL1A/COL3A) were preferentially detected by biopsies. Tape-strips identified more DEGs between AD and non-AD (3157 DEGs) then biopsies (44 DEGs). Tape-strips also detected higher levels of bacterial mRNA than biopsies. Conclusions: This study concludes that tape-strips and biopsies each demonstrate respective advantages for measuring gene-expression changes in AD. Thus, the specific skin layers and genes of interest should be considered before selecting either method.

PURPOSE:To explore the genetic background of choroidal and ciliary body melanoma among children and young adults, with special focus on BAP1 germline variants in this age group. METHODS:Patients under the age of 25 and with confirmed choroidal or ciliary body melanoma were included in this retrospective, multicenter observational study. Nuclear BAP1 immunopositivity was used to evaluate the presence of functional BAP1 in the tumor. Next-generation sequencing using Ion Torrent platform was used to determine pathogenic variants of BAP1, EIF1AX, SF3B1, GNAQ and GNA11 and chromosome 3 status in the tumor or in DNA extracted from blood or saliva. Survival was analyzed using Kaplan-Meier estimates. RESULTS:The mean age at diagnosis was 17 years (range 5.0–24.8). A germline BAP1 pathogenic variant was identified in an 18-year-old patient, and a somatic variant, based mainly on immunohistochemistry, in 13 (42%) of 31 available specimens. One tumor had a somatic SF3B1 pathogenic variant. Disomy 3 and the absence of a BAP1 pathogenic variant in the tumor predicted the longest metastasis-free survival. Males showed longer metastasis-free survival than females (P = 0.018). CONCLUSIONS:We did not find a stronger-than-average BAP1 germline predisposition for choroidal and ciliary body melanoma among children and young adults compared to adults. Males had a more favorable survival and disomy 3, and the absence of a BAP1 mutation in the tumor tissue predicted the most favorable metastasis-free survival. A BAP1 germline pathogenic variant was identified in one patient (1%), and a somatic variant based mainly on immunohistochemistry in 13 (42%).

In order to support or refute the clinical suspicion of cranial giant cell arteritis (GCA), a supplemental imaging modality is often required. High-resolution black blood Magnetic Resonance Imaging (BB MRI) techniques with contrast enhancement can visualize artery wall inflammation in GCA. We compared findings on BB MRI without contrast enhancement with findings on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/low-dose computed tomography (2-[18F]FDG PET/CT) in ten patients suspected of having GCA and in five control subjects who had a 2-[18F]FDG PET/CT performed as a routine control for malignant melanoma. BB MRI was consistent with 2-[18F]FDG PET/CT in 10 out of 10 cases in the group with suspected GCA. In four out of five cases in the control group, the BB MRI was consistent with 2-[18F]FDG PET/CT. In this small population, BB MRI without contrast enhancement shows promising performance in the diagnosis of GCA, and might be an applicable imaging modality in patients., In order to support or refute the clinical suspicion of cranial giant cell arteritis (GCA), a supplemental imaging modality is often required. High-resolution black blood Magnetic Resonance Imaging (BB MRI) techniques with contrast enhancement can visualize artery wall inflammation in GCA. We compared findings on BB MRI without contrast enhancement with findings on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/low-dose computed tomography (2-[18F]FDG PET/CT) in ten patients suspected of having GCA and in five control subjects who had a 2-[18F]FDG PET/CT performed as a routine control for malignant melanoma. BB MRI was consistent with 2-[18F]FDG PET/CT in 10 out of 10 cases in the group with suspected GCA. In four out of five cases in the control group, the BB MRI was consistent with 2-[18F]FDG PET/CT. In this small population, BB MRI without contrast enhancement shows promising performance in the diagnosis of GCA, and might be an applicable imaging modality in patients.

Purpose This double-blinded randomized clinical trial aimed to evaluate the efficacy of injecting allogeneic adipose-derived mesenchymal stem cells (ASCs) into the lacrimal gland (LG) for the treatment of dry eye disease (DED) secondary to Sjögren's syndrome (SS). Methods Fifty-four participants with severe DED secondary to SS were included and allocated to either ASCs (n = 20), vehicle (n = 20), or a non-randomized observation group (n = 14). The intervention groups received a single injection of either ASCs or an active comparator (vehicle, Cryostor® CS10) into the LG in one eye, while the observation group received lubricating eye drops only. The primary outcome measure was changes in Ocular Surface Disease Index (OSDI) score and secondary outcome measures were non-invasive tear break-up time, tear meniscus height, Schirmer's test, and Oxford score within a 12-month follow-up. Results A significant reduction in OSDI score was observed in the ASCs and vehicle groups compared to the observation group. In addition, the ASCs group demonstrated a significant increase in non-invasive tear break-up time compared to the vehicle group at the 4-week follow-up and to the observation group at the 12-month follow-up. A significant improvement in ocular surface staining, tear osmolarity, and Schirmer test score from baseline was also observed in the ASCs group; however, these changes were not significant compared to the other groups. Conclusion Improvement of subjective and objective signs and symptoms of DED was observed in both intervention groups following injection into the LG compared to the observation group. Future studies should investigate the mode-of-action of both injection treatments., Purpose: This double-blinded randomized clinical trial aimed to evaluate the efficacy of injecting allogeneic adipose-derived mesenchymal stem cells (ASCs) into the lacrimal gland (LG) for the treatment of dry eye disease (DED) secondary to Sjögren's syndrome (SS). Methods: Fifty-four participants with severe DED secondary to SS were included and allocated to either ASCs (n = 20), vehicle (n = 20), or a non-randomized observation group (n = 14). The intervention groups received a single injection of either ASCs or an active comparator (vehicle, Cryostor® CS10) into the LG in one eye, while the observation group received lubricating eye drops only. The primary outcome measure was changes in Ocular Surface Disease Index (OSDI) score and secondary outcome measures were non-invasive tear break-up time, tear meniscus height, Schirmer's test, and Oxford score within a 12-month follow-up. Results: A significant reduction in OSDI score was observed in the ASCs and vehicle groups compared to the observation group. In addition, the ASCs group demonstrated a significant increase in non-invasive tear break-up time compared to the vehicle group at the 4-week follow-up and to the observation group at the 12-month follow-up. A significant improvement in ocular surface staining, tear osmolarity, and Schirmer test score from baseline was also observed in the ASCs group; however, these changes were not significant compared to the other groups. Conclusion: Improvement of subjective and objective signs and symptoms of DED was observed in both intervention groups following injection into the LG compared to the observation group. Future studies should investigate the mode-of-action of both injection treatments.

Purpose: To investigate ophthalmic onset manifestations and the impact of diagnostic delay on the prognosis in infants (<1 year) diagnosed with a brain tumour. Methods: A retrospective population-based nationwide study of infants diagnosed with a brain tumour between 2007 and 2017 in Denmark. Data was retrieved from the Danish Childhood Cancer Registry, the National Danish Health registries, and medical files. Primary outcome measures included symptoms, clinical findings, time to diagnosis and survival. Results: Thirty-seven infants were diagnosed with a brain tumour in Denmark between 2007 and 2017. In total, 19/37 infants (51%, 95% CI: 34–68) had ophthalmic manifestations at any time prior to or at diagnosis; and in 6/37 (16%, 95% CI: 6–32) ophthalmic manifestations were the initial symptom. The most common ophthalmic manifestations were strabismus (n = 7), sunset eyes (n = 6), nystagmus (n = 4), reduced pupillary light reflex (n = 4), and/or decreased vision (n = 4). The median number of symptoms per infant at the time of diagnosis was three (range 0–9). The median diagnostic delay was 26 days (range 0–283, IQR: 6;90). 5-year survival rate was 75% (95% CI: 61–90) and all children with diagnostic delay > 100 days (n = 9, 24%) were still alive at the end of follow-up (median 6.3 years, range 2.2–10.2). Conclusion: We provide an overview of symptoms and clinical signs in a nation-wide series of infants with CNS tumours and demonstrate that ophthalmic manifestations are frequently observed in infants prior to diagnosis, but, often in combination with other clinical signs. The diagnostic delay was substantial for a large part of the infants, but this was not associated with increased mortality.

We report a rare case of a lacrimal sac angioleiomyoma. A 56-year-old woman complained of pain in the right medial canthal region over a period of 2 years. There were no complaints of epiphora or ocular infection, and no visible or palpable masses in the medial canthal region. Computed tomography scan revealed a solid tumor of the lacrimal sac expanding to the nasolacrimal duct and protruding under the inferior turbinate. The tumor was removed by external dacryocystectomy combined with endonasal, endoscopic anterior turbinectomy, and nasal mucosal resection. Histological and immunohistological findings were consistent with an angioleiomyoma of the venous type. There was no recurrence of the tumor at the three-year follow-up. Angioleiomyomas should be included in the differential diagnosis of lacrimal sac tumors. The definitive diagnoses rely on histology and immunohistological reactions. The treatment is complete surgical resection.