"More Guts Than Brains?"-The Role of Gut Microbiota in Idiopathic Intracranial Hypertension.

BACKGROUND: Idiopathic intracranial hypertension syndrome (IIH) is most common among obese women. Weight loss is an important factor in improving papilledema. Over the last decade, growing evidence has identified gut microbiota as a potential factor in the pathophysiology of obesity. Accordingly, we investigated whether the gut microbiome is modified in IIH patients compared with healthy controls, and provide possible new treatment venues. METHODS: Shotgun metagenomic sequencing of the gut microbiome of 25 cases of IIH patients (according to the modified Dandy criteria) and 20 healthy controls. Participants were further stratified according to their body mass index. The total DNA from each sample was extracted using the PureLink Microbiome DNA Purification Kit A29789 (Invitrogen, Thermo Fisher Scientific, US). Library preparation was performed using the Nextera DNA Flex Library Prep Kit. Samples were sequenced on the Illumina Novaseq 6000 device. A list of bacterial species that significantly differed between the IIH patients and healthy controls was produced in addition to species diversity. In addition, patients' cohort alone was analyzed, (excluding the healthy controls), and the effect of acetazolamide treatment on their gut microbiota was analyzed. RESULTS: IIH patients have a lower diversity of bacterial species compared with healthy individuals. These bacteria, that is, Lactobacillus ruminis (L. ruminis) (p<6.95E-08), Atopobium parvulum (p<3.9E-03), Megamonas hypermegale (p<5.61E-03), Ruminococcus gnavus (p<1.29E-02), MEL.A1 (p<3.04E-02), and Streptococcus sp. I-G2 (p<3.04E-02), were previously characterized with beneficial health effects. Moreover, we found that Lactobacillus brevis, a beneficial bacterium as well, is more abundant in acetazolamide treated patients (p<7.07E-06). CONCLUSIONS: Gut microbiota plays a potential role in IIH etiology and therefore, can provide a promising new treatment approach for this disease.

[WHEN IT SNOWS ALL YEAR ROUND - VISUAL SNOW].

INTRODUCTION: Visual snow is a neurological condition manifested as a prolonged visual experience of small flickering dots encompassing the entire visual field with additional visual and sensory-neural symptoms. The pathogenesis of this disturbance is unknown, although much progress has been made in recent years. The disturbance has been better defined and characterized. Additional insight into the pathological processes that play a role in this phenomenon has been gained, and different treatment modalities have been tried, some with better results. The purpose of this review is to increase awareness of this syndrome.

[MINIMALLY INVASIVE GLAUCOMA SURGERIES].

INTRODUCTION: The goal of all glaucoma surgery is to lower eye pressure to prevent or reduce damage to the optic nerve. Standard glaucoma surgeries - trabeculectomy, ExPRESS shunts and external tube-shunts like the Ahmed and Baerveldt valves - are major surgeries. While they are very often effective at lowering eye pressure and preventing progression of glaucoma, they have a long list of potential complications. Minimal invasive glaucoma surgery (MIGS) is a group of operations that have been developed in recent years to reduce some of the complications of most standard glaucoma surgeries. MIGS procedures work by using microscopic-sized equipment and tiny incisions. The purpose of this study is to review the available MIGS currently in use, their benefits and limitations.

A genetic survey of patients with familial idiopathic intracranial hypertension residing in a Middle Eastern village: genetic association study.

BACKGROUND: The aim of this study was to determine whether genetic variants are associated with idiopathic intracranial hypertension (IIH) in a unique village where many of the IIH patients have familial ties, a homogenous population and a high prevalence of consanguinity. Several autosomal recessive disorders are common in this village and its population is considered at a high risk for genetic disorders. METHODS: The samples were genotyped by the Ilumina OmniExpress-24 Kit, and analyzed by the Eagle V2.4 and DASH software package to cluster haplotypes shared between our cohort. Subsequently, we searched for specific haplotypes that were significantly associated with the patient groups. RESULTS: Fourteen patients and 30 controls were included. Samples from 22 female participants (11 patients and 11 controls) were evaluated for haplotype clustering and genome-wide association studies (GWAS). A total of 710,000 single nucleotide polymorphisms (SNPs) were evaluated. Candidate areas positively associated with IIH included genes located on chromosomes 16, 8 (including the CA5A and BANP genes, p < 0.01), and negatively associated with genes located on chromosomes 1 and 6 (including PBX1, LMX1A, ESR1 genes, p < 0.01). CONCLUSIONS: We discovered new loci possibly associated with IIH by employing a GWAS technique to estimate the associations with haplotypes instead of specific SNPs. This method can in all probability be used in cases where there is a limited amount of samples but strong familial connections. Several loci were identified that might be strong candidates for follow-up studies in other well-phenotypes cohorts.

XEN45 Gel Stent Combined with Healaflow Injectable Viscoelastic Implant.

Purpose: To introduce a potential solution for failed glaucoma surgeries by proposing an optional surgical procedure in conjunction with the use of Healaflow (Anteis S.A., Geneva, Switzerland) as a spacer, which may potentially reduce the failure rate. Case Presentation. We present the outcomes of a surgical procedure involving the inferonasal implantation of an ab interno XEN gel stent (Allergan, Dublin, Ireland) in a 74-year-old male patient who was experiencing uncontrolled advanced glaucoma in his left eye. It is important to note that the patient had previously undergone several glaucoma surgeries and procedures in the same eye. During this particular procedure, we utilized Healaflow as a spacer by implanting the stent within a subconjunctival Healaflow "bubble." At 6 months postoperatively, intraocular pressure remained on target. There was no need for additional topical medications, and no change in visual acuity was observed. Conclusion: For patients with a history of unsuccessful glaucoma surgeries and who are unsuitable candidates for tube shunt procedures or transscleral diode cyclophotocoagulation, an alternative option involves implanting the XEN45 stent in the inferior nasal region in conjunction with the use of subconjunctival Healaflow. This combined approach may provide a potential solution for managing glaucoma in these patients.

Efficacy of the XEN45 Implant in Advanced to End-stage Glaucoma Patients.

Purpose: To report the efficacy of the XEN45 implant in advanced to end-stage glaucoma patients, after a 6 months follow-up. Methods: Retrospective, noncomparative electronic health record audit of patients who had undergone an XEN45 procedure. The main outcome measures were intraocular pressure (IOP) reduction and the number of antihypertensive medications. Secondary outcome measures were the rates of early postoperative complications. Complete and qualified success; failure and hypotony were defined according to the World Glaucoma Association guidelines (Shaarawy TM et al.). Needling rates and short-term complications were assessed and a subgroup analysis was performed. Results: A total of 39 eyes with advanced to end stage-glaucoma were included. Twenty eyes (51%) had undergone combined cataract surgery and 19 (49%), the XEN45 procedure alone. Mean IOP decreased from 19.67 ± 7.87 mm Hg to 13.18 ± 6.09 mm Hg; the number of medications decreased from a median use of 4 (IQR 2-5) to 0 (IQR 0-1). Complete success was achieved in 24 (61.5%) of the eyes, qualified success in 10 (25.6%), and failure in five (12.82%). Needling was required in 15 (38.46%) of the eyes at 6 months. Choroidal detachment occurred in eight (20.51%) eyes, numerical hypotony (IOP ≤ 5 mm Hg) at day 1 was noted in seven (17.95%) eyes with a full resolution by 2 weeks. Conclusion: In this short-term follow-up, we have seen that XEN45 is a viable, effective, and safe procedure utilized in advanced to end-stage glaucoma patients. Treating cases of significant hypotony using AC reformation with sulfur hexafluoride (SF6) is a safe and effective procedure. How to cite this article: Hindi I, Berkowitz E, Waizer I, et al. Efficacy of the XEN45 Implant in Advanced to End-stage Glaucoma Patients. J Curr Glaucoma Pract 2022;16(2):84-90.

Selective Laser Trabeculoplasty for Steroid-Induced Ocular Hypertension following Endothelial Keratoplasty.

Purpose: To examine the safety and efficacy of selective laser trabeculoplasty (SLT) in patients responding to topical steroids with elevated intraocular pressure following endothelial keratoplasty.Methods: Patients that underwent Descemet Membrane Endothelial Keratoplasty (DMEK) or Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) were offered SLT as first-line therapy if they presented with steroid response and met inclusion criteria. Patient demographics, best-corrected visual acuity (BCVA), steroid and glaucoma regimens were recorded before and after SLT.Results: Twelve eyes of eight patients were recruited to the study. All patients demonstrated a reduction in IOP and only one patient remained on anti-glaucoma drops after SLT. The mean (±SD) reduction in IOP following SLT was 8.8 (±4.9) mmHg (p < 0.0001). BCVA remained stable and no adverse events following treatment were observed.Conclusions: SLT may be a safe and effective treatment option that reduces topical antihypertensive burden while allowing continuance of corticosteroids in steroid-responsive eyes at high risk of rejection following endothelial keratoplasty. Larger randomized studies are needed to compare SLT efficacy with topical medication in this patient group and to review any impact on graft survival and glaucoma progression.

Discrete limbal epithelial stem cell populations mediate corneal homeostasis and wound healing.

The accessibility and transparency of the cornea permit robust stem cell labeling and in vivo cell fate mapping. Limbal epithelial stem cells (LSCs) that renew the cornea are traditionally viewed as rare, slow-cycling cells that follow deterministic rules dictating their self-renewal or differentiation. Here, we combined single-cell RNA sequencing and advanced quantitative lineage tracing for in-depth analysis of the murine limbal epithelium. These analysis revealed the co-existence of two LSC populations localized in separate and well-defined sub-compartments, termed the "outer" and "inner" limbus. The primitive population of quiescent outer LSCs participates in wound healing and boundary formation, and these cells are regulated by T cells, which serve as a niche. In contrast, the inner peri-corneal limbus hosts active LSCs that maintain corneal epithelial homeostasis. Quantitative analyses suggest that LSC populations are abundant, following stochastic rules and neutral drift dynamics. Together these results demonstrate that discrete LSC populations mediate corneal homeostasis and regeneration.

Visual Snow: A Case Series from Israel.

Our aim was to examine the symptoms and clinical characteristics of visual snow in a group of 6 patients from a Department of Ophthalmology and a Department of Neurology. Visual snow is now recognized as a true physiological disorder. Previously, physicians unaware of this syndrome may have misinterpreted its symptoms as a persistent visual aura. By promoting awareness of this syndrome, greater quantitative and qualitative research may expand our understanding and treatment of this disorder.

Traumatic Optic Neuropathy and Monocular Blindness following Transnasal Penetrating Optic Canal Injury by a Wooden Foreign Body.

PURPOSE: To report a case of right eye blindness due to a penetrating injury in the contralateral nostril. METHODS: This is a case report of a 67-year-old patient who presented to the emergency room complaining of transient blurred vision in his right eye after falling on a small branch with no apparent injury besides minor lacerations. The following day, the patient experienced blindness in the right eye. Physical examination revealed small lacerations on his left forehead and optic neuropathy on the right side with no other obvious discerning physical or imaging abnormalities. RESULTS: After elevated suspicion and reassessment of the neuroimaging findings, a radiolucent track was observed in the nasal cavity, continuing up from the left nostril to the right optic nerve. Transnasal endoscopic surgery was performed and a long wooden branch was removed from the nasal cavity. CONCLUSION: A nasally penetrating wooden foreign body can cause traumatic optic neuropathy and vision loss on the unaffected side and can be very difficult to locate and image without any clear external evidence as to its presence. This case highlights the importance of maintaining a high level of suspicion in these types of cases.

IgG4-Related Disease Presenting as Isolated Scleritis.

A rare case of IgG4-related disease (IgG4-RD) manifesting as nodular scleritis is presented in a 20-year-old female. Patient complained of left eye pain and redness for one week. Ocular examination together with ancillary testing led to the diagnosis of nodular scleritis. Since the patient did not show apparent improvement after one week of systemic steroidal treatment, she underwent a biopsy of the affected area revealing histopathological characteristics of IgG4-RD. Long-term treatment with corticosteroids and a steroid-sparing agent (methotrexate) led to significant improvement in signs and symptoms. This case highlights the significance of IgG4-RD in the differential diagnosis of scleritis and raises the question as to whether various organs affected by IgG4-RD may have different underlying pathophysiological mechanisms in which pathogenic T cells play a role.

A Method for Lineage Tracing of Corneal Cells Using Multi-color Fluorescent Reporter Mice.

Lineage tracing experiments define the origin, fate and behavior of cells in a specific tissue or organism. This technique has been successfully applied for many decades, revealing seminal findings in developmental biology. More recently, it was adopted by stem cell biologists to identify and track different stem cell populations with minimal experimental intervention. The recent developments in mouse genetics, the availability of a large number of mouse strains, and the advancements in fluorescent microscopy allow the straightforward design of powerful lineage tracing systems for various tissues with basic expertise, using commercially available tools. We have recently taken advantage of this powerful methodology to explore the origin and fate of stem cells at the ocular surface using R26R-Confetti mouse. This model offers a multi-color genetic system, for the expression of 4 fluorescent genes in a random manner. Here we describe the principles of this methodology and provide an adaptable protocol for designing lineage tracing experiments; specifically for the corneal epithelium as well as for other tissues.