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.

Eyes open on stem cells.

Recently, the murine cornea has reemerged as a robust stem cell (SC) model, allowing individual SC tracing in living animals. The cornea has pioneered seminal discoveries in SC biology and regenerative medicine, from the first corneal transplantation in 1905 to the identification of limbal SCs and their transplantation to successfully restore vision in the early 1990s. Recent experiments have exposed unexpected properties attributed to SCs and progenitors and revealed flexibility in the differentiation program and a key role for the SC niche. Here, we discuss the limbal SC model and its broader relevance to other tissues, disease, and therapy.

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.

"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.

Short-term anterior chamber inflammation in phacoemulsification with and without Ex-Press glaucoma implant.

PURPOSE: The aim of this study was to investigate the incidence of clinically significant anterior chamber inflammation in a combined surgery, namely, phacoemulsification and Ex-Press miniature glaucoma device implantation, compared to phacoemulsification alone. METHODS: A retrospective comparative study of a consecutive series of 210 participants above 18 years of age diagnosed with significant cataract and who required glaucoma surgery, namely, Ex-Press miniature glaucoma device implantation or cataract alone in one or both eyes. All were operated on by a single experienced glaucoma surgeon in a single medical center. A total of 231 eyes were included in this study. All cases underwent an uneventful surgery and were examined the day following the surgery for visual acuity, intraocular pressure, and signs of excessive anterior chamber inflammation (Standardization of Uveitis Nomenclature grading ⩾ 3). RESULTS: The combined group included 55 eyes of 51 patients, of whom 15 (27.3%) demonstrated excessive anterior chamber inflammation. The phacoemulsification group included 176 eyes of 159 patients, of whom 12 (6.7%) demonstrated excessive anterior chamber inflammation. Visual acuity and intraocular pressure measurements showed no statistically significant difference between the two groups. CONCLUSION: The Ex-Press glaucoma device is efficient, safe, and known for its inert nature. However, combination of this procedure with phacoemulsification surgery might result in a condition encouraging excessive inflammation, which eventually could lead to excessive anterior chamber inflammations if not treated vigorously. Emphasizing and recognizing the risks, especially in glaucoma patients, is important.

Corneal Perforation after Nd: YAG Capsulotomy: A Case Report and Literature Review.

BACKGROUND: Nd: YAG capsulotomy is the treatment of choice for posterior capsular opacification after cataract surgery. We report a case of corneal perforation following Nd:YAG capsulotomy in a patient with systemic scleroderma. CASE PRESENTATION: A 69-year-old woman presented with acute onset of blurred vision 2 weeks following Nd:YAG laser capsulotomy for posterior subcapsular opacification. On examination, her best-corrected visual acuity was 1/120, and bio-microscopy revealed a central full-thickness corneal laceration. Conservative treatment consisted of topical ocular antibiotics, cycloplegics, hypotensive drops and a soft therapeutic contact lens. Her final visual acuity improved to 6/18 with resolution of the corneal laceration. CONCLUSION: The possibility of corneal perforation after Nd-YAG capsulotomy in patients with systemic scleroderma and connective tissue disease should be borne in mind when treating such patients.

[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.

SOX2 Regulates P63 and Stem/Progenitor Cell State in the Corneal Epithelium.

Mutations in key transcription factors SOX2 and P63 were linked with developmental defects and postnatal abnormalities such as corneal opacification, neovascularization, and blindness. The latter phenotypes suggest that SOX2 and P63 may be involved in corneal epithelial regeneration. Although P63 has been shown to be a key regulator of limbal stem cells, the expression pattern and function of SOX2 in the adult cornea remained unclear. Here, we show that SOX2 regulates P63 to control corneal epithelial stem/progenitor cell function. SOX2 and P63 were co-expressed in the stem/progenitor cell compartments of the murine cornea in vivo and in undifferentiated human limbal epithelial stem/progenitor cells in vitro. In line, a new consensus site that allows SOX2-mediated regulation of P63 enhancer was identified while repression of SOX2 reduced P63 expression, suggesting that SOX2 is upstream to P63. Importantly, knockdown of SOX2 significantly attenuated cell proliferation, long-term colony-forming potential of stem/progenitor cells, and induced robust cell differentiation. However, this effect was reverted by forced expression of P63, suggesting that SOX2 acts, at least in part, through P63. Finally, miR-450b was identified as a direct repressor of SOX2 that was required for SOX2/P63 downregulation and cell differentiation. Altogether, we propose that SOX2/P63 pathway is an essential regulator of corneal stem/progenitor cells while mutations in SOX2 or P63 may disrupt epithelial regeneration, leading to loss of corneal transparency and blindness. Stem Cells 2019;37:417-429.

Clinical Efficacy and Safety of the EX-PRESS Filtration Device in Patients with Advanced Neovascular Glaucoma and Proliferative Diabetic Retinopathy.

BACKGROUND: The prognosis of conventional filtration surgery in eyes with neovascular glaucoma (NVG) is limited due to increased fibrovascular proliferation or bleeding. This study aims to evaluate the safety and efficacy of the EX-PRESS filtration device in the management of NVG associated with proliferative diabetic retinopathy (PDR). METHODS: In this retrospective case series, we reviewed the medical records of patients diagnosed as having NVG associated with PDR who underwent EX-PRESS filtration surgery. The main outcome measures were: postoperative intraocular pressure (IOP), the percent of IOP drop, the number of glaucoma medications, visual acuity, and complications of surgery. Successful surgery was defined as an IOP <22 mm Hg and >5 mm Hg with or without additional glaucoma surgery, and no loss of light perception or less than a 2-line decrease on the Snellen chart of the best corrected visual acuity (BCVA). RESULTS: Five patients (5 eyes) were included in this study. The mean preoperative IOP was 33.4 ± 5.9 mm Hg compared to an IOP of 17.0 ± 3.0 mm Hg at the last follow-up (p = 0.003). The mean number of preoperative anti-glaucoma medications was 3.8 ± 0.4 compared to 2.2 ± 1.5 (p = 0.06) at the last follow-up visit. Final visual acuity improved or stabilized within 1 Snellen line in all 5 patients. Three patients had a "hypertensive phase" (defined as an IOP >21 mm Hg during the first 6 postoperative months) which resolved within 2 months. Two patients developed a hyphema that resolved spontaneously. None of the patients experienced any serious complications. CONCLUSION: EX-PRESS filtration device has a good IOP-lowering effect and a low rate of complications in patients with advanced NVG associated with PDR. In addition, there was no loss of light perception or no line decrease of the BCVA.

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.