Vision screening and refraction of Greenlandic schoolchildren.

PURPOSE: To estimate the prevalence of amblyopia and refractive errors among 6-year-old children in Greenland and to assess the impact of incorporating autorefraction, stereoacuity and near visual acuity testing into vision screening. METHODS: In this cross-sectional study, 517 children (238 girls and 279 boys) from 21 locations in Greenland were screened using HOTV charts for distance and near visual acuity (VA), stereoacuity test and non-cycloplegic autorefraction. Referral criteria for further ophthalmological examination included a VA of ≥0.2 logMAR on the worse-seeing eye or an interocular VA difference of ≥2 lines. RESULTS: Initial screening identified amblyopia (defined as VA of ≥0.3 logMAR) in 7% (unilateral) and 3% (bilateral) of children. However, subsequent ophthalmological examinations confirmed amblyopia in under 40% of referrals. Significant interocular VA differences were found in 9%. The prevalence of refractive errors at the screening was 3% for myopia (≤-0.5 dioptres), 10% for hyperopia (>+2.0 dioptres) and 14% for astigmatism (≤-1.00 dioptres), while the corresponding prevalences at the ophthalmological examination were 4% for myopia, 8% for hyperopia and 6% for astigmatism. Combining screening measurements increased the positive predictive values, thereby enhancing screening accuracy. Specifically, the incorporation of autorefraction or stereoacuity with distance VA demonstrated to be the most effective combination. Six percent of the children were prescribed glasses after the screening procedure. CONCLUSION: This study provides the first visual profile of Greenlandic schoolchildren. Incorporating autorefraction, stereoacuity and near visual acuity in vision screenings enhanced the efficacy of detection of vision anomalies. Although this may lead to more false positives, accurate screening is crucial in regions with limited ophthalmological resources.

Eyelid sebaceous gland carcinoma: a protocol for a systematic review and meta-analysis of clinicopathological studies of prevalence.

INTRODUCTION: Sebaceous gland carcinoma (SGC) of the eyelid is an aggressive tumour with the ability to metastasise and an increased morbidity. Controversies regarding the epidemiology of this malignant eyelid tumour is widespread in the scientific literature. Western reports repeatedly describes eyelid SGC as a rare occurring tumour in general, accounting for 1%-3% of all eyelid tumours, however studies from Asia have uncovered a higher frequency of eyelid SGC including 54% of all eyelid tumours in Japan, and 43%-56% in India. We wish to retrieve observational data of eyelid SGC prevalence in proportion to total eyelid tumours, from pathological studies published worldwide to resolve this controversy. METHODS AND ANALYSIS: We will search Ovid Medline, EMBASE, Cochrane Central Register of Controlled Trials, Scopus and Google Scholar to identify published reports on eyelid SGC prevalence proportions, aiming to clarify the incidence of the tumour. We will include observational clinicopathological studies reporting prevalence with confirmed histopathology. No limitations on publication date or language will be applied. Data from the individual studies and study quality will be extracted by two individual reviewers. Study quality will be assessed using the JBI Critical Appraisal Instrument for Studies Reporting Prevalence Data. Raw proportions will be transformed and pooled using a random effects model for meta-analysis. And subgroup analysis according to geography will be performed. If data are deemed unsuitable for a meta-analysis, a narrative synthesis will be presented. We will judge the certainty of evidence and present whether this has an overall effect on the results. The results may shed light on a long-standing academic disparity of the scientific literature. ETHICS AND DISSEMINATION: This systematic review does not require ethical approval. The results of this proposed review will be the subject to a publication in an international peer-reviewed journal within the ophthalmic or pathological specialty. PROSPERO REGISTRATION NUMBER: CRD42023487141.

Topical glaucoma medications - Possible implications on the meibomian glands.

One of the most common causes of blindness on a global scale is glaucoma. There is a strong association between glaucoma and increased intraocular pressure (IOP). Because of this, adequate IOP-lowering is the most important treatment strategy, mostly through topical eyedrops. Well-functioning meibomian glands are paramount for maintaining a stable tear film, and their dysfunction is the most common cause of dry eye disease. There is a growing concern that both topical glaucoma medications themselves and their added preservatives damage the meibomian glands, and consequently, the ocular surface. Preserved topical glaucoma medications appear to cause dysfunction and atrophy of the meibomian glands. Upon comparison, preserved formulations caused more symptoms of dry eye, tear film instability, inflammatory changes and meibomian gland dropout than the preservative-free counterpart. However, although seemingly less detrimental, unpreserved alternatives may diminish glandular efficacy, and, depending on the active ingredient, lead to glandular death. This negatively impacts quality of life, adherence to treatment regimens and prognosis. In this review, we explore the available evidence regarding the effects of IOP-lowering eye drops on the meibomian glands.

Thyroid dysfunction and exudative age-related macular degeneration - A longitudinal nationwide registry-based cohort study.

PURPOSE: The association between thyroid dysfunction and exudative age-related macular degeneration (AMD) is unknown. METHODS: In this Danish longitudinal nationwide registry-based cohort study we included all Danish residents aged 50-100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD. Thyroid dysfunction was classified as two consecutive redeemed prescriptions of thyroid hormones (hypothyroidism) or anti-thyroid medication (hyperthyroidism). Exudative AMD was classified as an ICD diagnosis of AMD and a code for anti-VEGF treatment. All patients are treated for exudative AMD in a hospital in Denmark, and we therefore have complete registration of this patient group. RESULTS: We included 2 087 305 individuals, of which 1 072 567 (51.4%) were women; 59 318 (2.8%) had hypothyroidism, and 33 922 (1.6%) had hyperthyroidism. During a median follow-up of 11 years, 26 998 (1.3%) people developed exudative AMD. Hypothyroidism (adjusted hazard ratio [HR]: 1.17; 95% confidence interval [CI] 1.10-1.25; p < 0.001) and hyperthyroidism (HR: 1.23; 95% CI:1.13-1.34; p < 0.001) were both associated with the development of exudative AMD. The age-stratified analyses yielded similar results to the main analyses, except that the risks were exaggerated in the older part of the population. CONCLUSION: This is the first longitudinal nationwide study showing that both hypo- and hyperthyroidism are associated with an increased risk of exudative AMD. AMD is a quantitative problem in the population and our findings could have a public health impact. Further studies are needed to study the underlying mechanisms of the association.

Presence and development of diabetic retinopathy in 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy.

PURPOSE: To evaluate the five-year incidence of diabetic retinopathy (DR) and associated risk markers in patients with type 1 diabetes in the national Danish DR-screening programme. METHODS: Based on national data, we included all 16 999 patients with type 1 diabetes in the Danish Registry of Diabetic Retinopathy, who attended the national screening programme in the period 2013-2018. According to the worse eye at first screening, DR was classified (levels 0-4) and linked with various national health registries to retrieve information on diabetes duration, systemic comorbidity, and medication. RESULTS: At first screening, median age and duration of diabetes were 45.0 and 16.7 years, and 57.5% were males. The prevalence and five-year incidences for DR and progression to proliferative DR (PDR) were 44.2%, 8.9% and 2.0%, respectively. In multivariable Cox models, the incidence endpoints were associated with duration of diabetes (hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.63-1.89, and HR 2.04, 95% CI 1.73-2.40 per 10 years), moderately low Charlson Comorbidity Index score (HR 1.27, 95% CI 1.10-1.47, and HR 2.80, 95% CI 2.23-3.51), and use of blood pressure lowering medication (HR 1.20, 95% CI 1.05-1.36, and HR 1.98, 95% CI 1.53-2.57). CONCLUSION: In a study of all patients with type 1 diabetes from the Danish DR-screening programme, we identified duration of diabetes, systemic disease and use of anti-hypertensive treatment as consistent risk markers for incident and progressive DR.

Optic disc drusen: Dystrophic calcification, a potential target for treatment.

Optic disc drusen (ODD) are calcified, acellular bodies, seen in the optic nerve head of up to 2% of the population. Although seldomly affecting visual acuity, visual field defects are common, and severe, ischemic complications causing irreversible vision loss are known to occur. Different treatment strategies for ODD have been explored, but so far without success. This review focuses on the unique, calcified property of ODD, describing what we know about ODD pathogenesis and previously tried treatment strategies. In this context, we discuss current knowledge about calcium and pathological calcifications, including intracranial and ocular calcifications. We also explore some of the obstacles that must be addressed to develop a therapy centred on the concept of calcification, should calcification be identified as a pathogenic factor contributing to vision loss.

The Pediatric and Young Adult Choroidal and Ciliary Body Melanoma Genetic Study, A Survey by the European Ophthalmic Oncology Group.

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%).

Comparing the effect of benzalkonium chloride-preserved, polyquad-preserved, and preservative-free prostaglandin analogue eye drops on cultured human conjunctival goblet cells

Purpose To investigate the effect of benzalkonium chloride (BAK)-preserved latanoprost and bimatoprost, polyquad (PQ)-preserved travoprost, and preservative-free (PF) latanoprost and tafluprost, all prostaglandin analogues (PGAs), on human conjunctival goblet cell (GC) survival. Furthermore, to investigate the effect of BAK-preserved and PF latanoprost on the cytokine secretion from GC. Methods Primary human conjunctival GCs were cultivated from donor tissue. Lactate dehydrogenase (LDH) and tetrazolium dye colorimetric (MTT) assays were used for the assessment of GC survival. A cytometric bead array was employed for measuring secretion of interleukin (IL)-6 and IL-8 from GC. Results BAK-preserved latanoprost and bimatoprost reduced cell survival by 28% (p = 0.0133) and 20% (p = 0.0208), respectively, in the LDH assay compared to a negative control. BAK-preserved latanoprost reduced cell proliferation by 54% (p = 0.003), BAK-preserved bimatoprost by 45% (p = 0.006), PQ-preserved travoprost by 16% (p = 0.0041), and PF latanoprost by 19% (p = 0.0001), in the MTT assay compared to a negative control. Only PF tafluprost did not affect the GCs in either assay. BAK-preserved latanoprost caused an increase in the secretion of pro-inflammatory IL-6 and IL-8 (p = 0.0001 and p = 0.0019, respectively) compared to a negative control, which PF latanoprost did not. Conclusion BAK-preserved PGA eye drops were more cytotoxic to GCs than PQ-preserved and PF PGA eye drops. BAK-preserved latanoprost induced an inflammatory response in GC. Treatment with PF and PQ-preserved PGA eye drops could mean better tolerability and adherence in glaucoma patients compared to treatment with BAK-preserved PGA eye drops. (AU)

RNA-sequencing of paired tape-strips and skin biopsies in atopic dermatitis reveals key differences.

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.

Effect of chlorhexidine, povidone-iodine and betadine antiseptic eye drops on cultured human conjunctival goblet cell survival.

PURPOSE: To compare the effect of the ocular antiseptic treatments 0.05% chlorhexidine, 5% povidone-iodine (PI) and 5% betadine on cell viability and mucin secretion of primary cultured human goblet cells (GCs). METHOD: GC viability was analysed using lactate dehydrogenase (LDH) and tetrazolium dye (MTT) colorimetric assays. Expression of mucin was visualised by immunohistochemical MUC5AC staining. RESULTS: PI and betadine significantly reduced GC survival compared to the control (mean cell survival 23 ± 6% and 23 ± 7%, respectively, p < 0.05), whereas chlorhexidine did not significantly affect GC viability (mean cell survival: 78 ± 17%), as measured by the LDH assay. Similar results were obtained from the MTT assay, where PI and betadine caused a significant loss of GCs (mean cell survival: 26 ± 12% and 26 ± 13%, respectively, p < 0.05). Chlorhexidine did not significantly alter GC survival compared to the control (mean cell survival: 79 ± 8%). PI and betadine caused a dispersion of mucin secretion, which chlorhexidine did not. CONCLUSION: The most used antiseptic treatments, PI and betadine, applied prior to ocular surgery are significantly more cytotoxic to conjunctival GCs than chlorhexidine treatment.

The Genetic Profile of Large B-Cell Lymphomas Presenting in the Ocular Adnexa.

To provide insights into targetable oncogenic pathways, this retrospective cohort study investigated the genetic profile of 26 patients with diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), and two patients with high-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL) presenting in the ocular adnexa. Pathogenic variants and copy number variations in 128 B-cell lymphoma-relevant genes were analyzed by targeted next-generation sequencing. Genetic subtypes were determined with the LymphGen algorithm. Primary ocular adnexal DLBCL-NOS constituted 50% (n = 14) and was generally characterized by non-germinal center B-cell origin (non-GCB) (n = 8, 57%), and LymphGen MCD subtype (n = 5, 36%). Primary ocular adnexal DLBCL-NOS presented pathogenic variants in genes involved in NF-κB activation and genes which are recurrently mutated in other extranodal lymphomas of non-GCB origin, including MYD88 (n = 4, 29%), CD79B (n = 3, 21%), PIM1 (n = 3, 21%), and TBL1XR1 (n = 3, 21%). Relapsed DLBCL-NOS presenting in the ocular adnexa (n = 6) were all of non-GCB origin and frequently of MCD subtype (n = 3, 50%), presenting with a similar genetic profile as primary ocular adnexal DLBCL-NOS. These results provide valuable insights into genetic drivers in ocular adnexal DLBCL-NOS, offering potential applications in future precision medicine.

Risk of Diabetic Retinopathy According to Subtype of Type 2 Diabetes.

Type 2 diabetes is a heterogeneous disease that can be subdivided on the basis of ß-cell function and insulin sensitivity. We investigated the presence, incidence, and progression of diabetic retinopathy (DR) according to subtypes of type 2 diabetes. In a national cohort, we identified three subtypes of type 2 diabetes: classical, hyperinsulinemic, and insulinopenic type 2 diabetes, based on HOMA2 measurements. From the Danish Registry of Diabetic Retinopathy we extracted information on level of DR. We used several national health registries to link information on comorbidity, medications, and laboratory tests. We found individuals with hyperinsulinemic type 2 diabetes were less likely to have DR at entry date compared with those with classical type 2 diabetes, whereas individuals with insulinopenic type 2 diabetes were more likely to have DR. In multivariable Cox regression analysis, individuals with hyperinsulinemic type 2 diabetes had a decreased risk of both incidence and progression of DR compared to those with classical type 2 diabetes. We did not find any clear difference in risk of incident or progression of DR in individuals with insulinopenic compared to classical type 2 diabetes. These findings indicate that subcategorization of type 2 diabetes is important in evaluating the risk of DR.

Heritability of tear fluid cytokines in healthy twins.

PURPOSE: Ocular surface disease is common and it is associated with elevated concentration levels of cytokines in tear fluid. Studies of the normal variation in tear fluid inflammatory markers are lacking. New knowledge may help guide research into ocular surface disease biomarkers and therapeutics. METHODS: In this prospective twin cohort study, healthy individuals were recruited from a population-based registry. Tear fluid was collected with the Schirmer test strips was submerged in phosphate buffered saline and stored at -80° before undergoing 27-cytokine multiplex immunoassay analysis. Broad-sense heritability (h2) of cytokine concentrations was analyzed. RESULTS: 90 participants (23 monozygotic and 22 dizygotic twin pairs) were included. Data availability allowed for heritability analysis of 15 cytokines, and a h2 >50% was seen for 10 cytokines. A statistical power of >80% was achieved for heritability analyses of the cytokines interferon gamma induced protein 10 (h2 = 94.8%), eotaxin (89.8%), interleukin 7 (86.6%), interleukin 1ß (82.2%) and monocyte chemoattractant protein 1 (68.2%). CONCLUSIONS: The tear fluid concentration of several analyzed cytokines was found to be highly heritable. A considerable amount of the inter-individual variation observed for the concentration of certain tear fluid cytokines can be linked to hereditary factors that cannot easily be modified by changing factors in the environment of patients. This suggests that a higher success in ocular surface disease drug discovery may be anticipated for drugs that have targets in specific populations, and points to the importance of emphasizing known preventive measures of ocular surface disease and examinations of close relatives of patients with ocular surface disease, such as dry eye disease.

Sinonasal DLBCL: molecular profiling identifies subtypes with distinctive prognosis and targetable genetic features.

ABSTRACT: Primary sinonasal diffuse large B-cell lymphoma (PSDLBCL) is a rare lymphoma with a variable prognosis and a unique relapse/dissemination pattern involving the central nervous system and skin. The underlying molecular mechanisms leading to this heterogeneity and progression pattern remain uncharted, hampering patient-tailored treatment. To investigate associated mechanisms, we analyzed clinical data and used immunohistochemistry, gene-expression profiling, cytogenetics, and next-generation sequencing in a cohort of 117 patients with PSDLBCL. The distribution in cell-of-origin (COO) was 68 (58%) activated B-cell (ABC), 44 (38%) germinal center B-cell (GCB), and 5 (4%) unclassifiable. COO was significantly associated with progression-free survival (PFS) and lymphoma-specific mortality (LSM) in both the overall cohort (5-year PFS: ABC, 43% vs GCB, 73%; LSM: ABC, 45% vs GCB, 14%) and in the subgroup of patients receiving immunochemotherapy (5-year PFS: ABC, 55% vs GCB, 85%; LSM: ABC, 28% vs GCB, 0%). ABC lymphomas were mainly MCD class, showing a high prevalence of MYD88 (74%) and CD79B (35%) mutations compared with GCB lymphomas (MYD88 23%; CD79B 10%) (P < .01). The ABC subtype frequently displayed cMYC/BCL2 coexpression (76% vs 18% GCB; P < .001) and HLA-II loss (48% vs 10% GCB; P < .001). PD-L1 expression and copy-number alterations were rare. All lymphomas were Epstein-Barr virus-negative. Our data suggest molecular profiling as a potent tool for detecting prognostic subgroups in PSDLBCL, exposing links to known relapse/dissemination sites. The ABC subgroup's MCD genetic features, shared with lymphomas at other nonprofessional lymphoid sites, make them potential candidates for targeted B-cell and toll-like receptor signaling therapy.

Diabetic retinopathy as an independent marker of cardiovascular disease in type 1 diabetes: Results from a nationwide longitudinal matched case-cohort study.

PURPOSE: To investigate diabetic retinopathy (DR) as a potential marker of cardiovascular disease (CVD) in adults with type 1 diabetes attending the Danish DR-screening programme and non-diabetes adults. METHODS: In this registry-based matched case-cohort study, we identified 16 547 adults with type 1 diabetes, who were registered in the Danish Registry of Diabetic Retinopathy (DiaBase). Each case was age- and sex-matched by five non-diabetes individuals (n = 82 399), and odds ratios (ORs) and hazard ratios (HRs) were estimated for incident and upcoming CVD in multivariable models. RESULTS: Adults with type 1 diabetes (median age 44.5 years, 57.6% male) were more likely to have prevalent CVD (OR 1.29; 95% CI, 1.20-1.38) and to develop CVD within 5 years (HR 1.19; 95% CI, 1.08-1.30) as compared to non-diabetes control. However, adults without DR were less likely to develop CVD (HR 0.84; 95% CI, 0.72-0.97) compared to the reference population. For adults with type 1 diabetes, there was an increasing risk for incident CVD for increasing levels of DR (HR 1.33, 1.95, 1.71 and 2.39 for DR-levels 1-4, respectively). Patients with CVD at the time of the first screening had a higher risk to develop DR during follow-up (HR 1.23; 95% CI, 1.02-1.49). CONCLUSION: In a nationwide matched case-cohort study adjusted for potential confounders, DR was identified as an independent marker of prevalent and incident CVD in type 1 diabetes with increasing risk demonstrated for higher levels of DR. Likewise, CVD also independently predicted the risk of incident DR.

Challenges in diagnosing canine spindle cell tumours using immunohistochemistry, illustrated by three nonpigmented malignant cases from the nictitating membrane.

BACKGROUND: Nonpigmented malignant spindle cell tumours of the membrana nictitans are rare in dogs. In twenty-three years only three cases have been diagnosed in Scandinavia. This study describes the three cases of malignant tumours of the membrana nictitans recorded by the Eye Pathology Section, University of Copenhagen, Denmark, with reference to the clinical appearance and work-up, the treatment and prognosis, and the histopathological description including immunohistochemistry. The three cases are compared to previous publications on canine tumours of the nictitating membrane. We emphasize the importance of using protocols that are adapted to the specific species such as dogs. Opposite the human tissue responses, we even need more than one marker when diagnosing melanomas in dogs. RESULTS: The dogs presented were an 8-year-old Dachshund, a 12-year-old Akita and a 14-year-old Shetland Sheepdog. All three dogs were entire females. All three nictitating membrane tumours developed on the right nictitating membrane as firm or multilobulated hyperaemic masses. Two of the tumours were macroscopically nonpigmented, the third being partly pigmented on the surface and ulcerated. According to the histopathology and for two of the cases immunohistochemistry with dog-adapted protocols the diagnoses included one hemangiosarcoma and two amelanotic melanomas. Tumour regrowth developed in all three cases and repeated resections were completed 1, 2 and 3 times, respectively, with recurrence experienced within 1.5 months - 3 years. CONCLUSIONS: Nonpigmented malignant spindle cell tumours of the canine membrana nictitans are rare. Treatment of choice should be complete excision with a minimal histologic tumour-free distance and in case of a recurrence a full resection of the nictitating membrane. We strongly recommend a dog-adapted protocol for immunohistochemistry.

Outcome of combined cataract surgery and iris prosthesis implantation in iris melanoma patients previously treated with iridocyclectomy: A national retrospective non-comparative case series.

PURPOSE: To examine complications, visual outcomes, photic patient-reported symptoms, corneal morphology, IOL tilt, and intraocular pressure after implantation of an intraocular lens (IOL) and iris prosthesis (IP) following iridocyclectomy. METHODS: Patients with previous iridocyclectomy treated with an IOL and IP at the Copenhagen University Hospital Rigshospitalet between 2007 and 2018 were included in this national retrospective non-comparative case series. The assessment encompassed BCVA, PRO questionnaire, corneal topography, and anterior segment OCT. RESULTS: 45 patients were included. Eight of 45 patients were previously treated with ruthenium-106 brachytherapy in conjunction with iridocyclectomy. Six of 45 patients developed endothelial dysfunction four of whom had received ruthenium-106 brachytherapy. Five of 45 patients had subluxation of the IOL/IP complex due to incomplete zonula apparatus. BCVA improved for all patients after lens surgery. 26 patients participated in the invited follow-up examination. 19 of 26 (73%) reported none or mild photic symptoms after IP instalment. Five (19%) reported ongoing severe photic symptoms. The corneal astigmatism significantly increased after iridocyclectomy but did not change after lens surgery. CONCLUSIONS: Implantation of an IOL and IP is a safe procedure, alleviating photic symptoms in most patients. It comes with higher risk of complications due to a more demanding procedure and larger surgical traumas from previous treatments. Ruthenium-106 brachytherapy increases the complication risk. Corneal astigmatism is induced by iridocyclectomy but does not change after lens surgery.

CSF hyperdynamics in rats mimicking the obesity and androgen excess characteristic of patients with idiopathic intracranial hypertension.

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.

Allogeneic mesenchymal stem cell therapy for dry eye disease in patients with Sjögren's syndrome: A randomized clinical trial.

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.

Comparing the effect of benzalkonium chloride-preserved, polyquad-preserved, and preservative-free prostaglandin analogue eye drops on cultured human conjunctival goblet cells.

PURPOSE: To investigate the effect of benzalkonium chloride (BAK)-preserved latanoprost and bimatoprost, polyquad (PQ)-preserved travoprost, and preservative-free (PF) latanoprost and tafluprost, all prostaglandin analogues (PGAs), on human conjunctival goblet cell (GC) survival. Furthermore, to investigate the effect of BAK-preserved and PF latanoprost on the cytokine secretion from GC. METHODS: Primary human conjunctival GCs were cultivated from donor tissue. Lactate dehydrogenase (LDH) and tetrazolium dye colorimetric (MTT) assays were used for the assessment of GC survival. A cytometric bead array was employed for measuring secretion of interleukin (IL)-6 and IL-8 from GC. RESULTS: BAK-preserved latanoprost and bimatoprost reduced cell survival by 28% (p = 0.0133) and 20% (p = 0.0208), respectively, in the LDH assay compared to a negative control. BAK-preserved latanoprost reduced cell proliferation by 54% (p = 0.003), BAK-preserved bimatoprost by 45% (p = 0.006), PQ-preserved travoprost by 16% (p = 0.0041), and PF latanoprost by 19% (p = 0.0001), in the MTT assay compared to a negative control. Only PF tafluprost did not affect the GCs in either assay. BAK-preserved latanoprost caused an increase in the secretion of pro-inflammatory IL-6 and IL-8 (p = 0.0001 and p = 0.0019, respectively) compared to a negative control, which PF latanoprost did not. CONCLUSION: BAK-preserved PGA eye drops were more cytotoxic to GCs than PQ-preserved and PF PGA eye drops. BAK-preserved latanoprost induced an inflammatory response in GC. Treatment with PF and PQ-preserved PGA eye drops could mean better tolerability and adherence in glaucoma patients compared to treatment with BAK-preserved PGA eye drops.