Biochemical-molecular-genetic biomarkers in the tear film, aqueous humor, and blood of primary open-angle glaucoma patients.

Introduction: Glaucoma is a chronic neurodegenerative disease, which is the leading cause of irreversible blindness worldwide. As a response to high intraocular pressure, the clinical and molecular glaucoma biomarkers indicate the biological state of the visual system. Classical and uncovering novel biomarkers of glaucoma development and progression, follow-up, and monitoring the response to treatment are key objectives to improve vision outcomes. While the glaucoma imaging field has successfully validated biomarkers of disease progression, there is still a considerable need for developing new biomarkers of early glaucoma, that is, at the preclinical and initial glaucoma stages. Outstanding clinical trials and animal-model study designs, innovative technology, and analytical approaches in bioinformatics are essential tools to successfully uncover novel glaucoma biomarkers with a high potential for translation into clinical practice. Methods: To better understand the clinical and biochemical-molecular-genetic glaucoma pathogenesis, we conducted an analytical, observational, and case-comparative/control study in 358 primary open-angle glaucoma (POAG) patients and 226 comparative-control individuals (CG) to collect tears, aqueous humor, and blood samples to be processed for identifying POAG biomarkers by exploring several biological pathways, such as inflammation, neurotransmitter/neurotrophin alteration, oxidative stress, gene expression, miRNAs fingerprint and its biological targets, and vascular endothelial dysfunction, Statistics were done by using the IBM SPSS 25.0 program. Differences were considered statistically significant when p ≤ 0.05. Results: Mean age of the POAG patients was 70.03 ± 9.23 years, and 70.62 ± 7.89 years in the CG. Malondialdehyde (MDA), nitric oxide (NO), interleuquin (IL)-6, endothelin-1 (ET-1), and 5 hydroxyindolacetic acid (5-HIAA), displayed significantly higher levels in the POAG patients vs. the CG (p < 0.001). Total antioxidant capacity (TAC), brain derived neurotrophic factor (BDNF), 5-hydroxy tryptamine (5-HT), solute carrier family 23-nucleobase transporters-member 2 (SLC23A2) gene, and the glutathione peroxidase 4 (GPX4) gene, showed significantly lower levelsin the POAG patients than in the CG (p < 0.001). The miRNAs that differentially expressed in tear samples of the POAG patients respect to the CG were the hsa miR-26b-5p (involved in cell proliferation and apoptosis), hsa miR-152-3p (regulator of cell proliferation, and extracellular matrix expression), hsa miR-30e-5p (regulator of autophagy and apoptosis), and hsa miR-151a-3p (regulator of myoblast proliferation). Discussion: We are incredibly enthusiastic gathering as much information as possible on POAG biomarkers to learn how the above information can be used to better steer the diagnosis and therapy of glaucoma to prevent blindness in the predictable future. In fact, we may suggest that the design and development of blended biomarkers is a more appropriate solution in ophthalmological practice for early diagnosis and to predict therapeutic response in the POAG patients.

Oxidative Stress Mediates Epigenetic Modifications and the Expression of miRNAs and Genes Related to Apoptosis in Diabetic Retinopathy Patients.

Knowledge on the underlying mechanisms and molecular targets for managing the ocular complications of type 2 diabetes mellitus (T2DM) remains incomplete. Diabetic retinopathy (DR) is a major cause of irreversible visual disability worldwide. By using ophthalmological and molecular-genetic approaches, we gathered specific information to build a data network for deciphering the crosslink of oxidative stress (OS) and apoptosis (AP) processes, as well as to identify potential epigenetic modifications related to noncoding RNAs in the eyes of patients with T2DM. A total of 120 participants were recruited, being classified into two groups: individuals with T2MD (T2MDG, n = 67), divided into a group of individuals with (+DR, n = 49) and without (-DR, n = 18) DR, and a control group (CG, n = 53). Analyses of compiled data reflected significantly higher plasma levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and significantly lower total antioxidant capacity (TAC) in the +DR patients compared with the -DR and the CG groups. Furthermore, the plasma caspase-3 (CAS3), highly involved in apoptosis (AP), showed significantly higher values in the +DR group than in the -DR patients. The microRNAs (miR) hsa-miR 10a-5p and hsa-miR 15b-5p, as well as the genes BCL2L2 and TP53 involved in these pathways, were identified in relation to DR clinical changes. Our data suggest an interaction between OS and the above players in DR pathogenesis. Furthermore, potential miRNA-regulated target genes were identified in relation to DR. In this concern, we may raise new diagnostic and therapeutic challenges that hold the potential to significantly improve managing the diabetic eye.

Updates on the utility of anterior segment optical coherence tomography in the assessment of filtration blebs after glaucoma surgery.

The formation of filtration blebs is the main drainage mechanism for reducing intraocular pressure after traditional incisional glaucoma surgery such as trabeculectomy and non-penetrating deep sclerotomy. Early and short-lasting blebs may also occur after canaloplasty. Bleb formation also plays an important role after the implantation of glaucoma drainage devices, including Minimally Invasive Glaucoma Surgery devices. Anterior segment optical coherence tomography (AS-OCT) is a rapid and non-invasive high-resolution imaging technique that has evolved in recent years to become a routine examination. Anterior segment optical coherence tomography (AS-OCT) provides key information in the assessment and follow-up of glaucoma surgery, especially in the assessment of filtration blebs. Thus, bleb morphology can be qualitatively classified into diffuse, cystic, encapsulated and flattened, and AS-OCT imaging can also provide several quantitative parameters of the bleb, such as total bleb height, bleb fluid-filled cavity height, bleb wall thickness, number of microcysts and trabeculectomy opening size. These parameters could have an impact on clinical management during follow-up because they may predict the success or failure of the surgery in the early and late postoperative periods. Additionally, they may also guide the procedures used to increase filtration and reduce intraocular pressure, such as bleb needling and laser suture lysis.

Three-year effectiveness and safety of the XEN gel stent as a solo procedure or in combination with phacoemulsification in open-angle glaucoma: a multicentre study.

PURPOSE: To assess the 3-year effectiveness and safety of the XEN gel stent implanted ab interno in open-angle glaucoma (OAG). METHODS: This study was a multicentre, retrospective chart review of consecutive patients with OAG who underwent ab-interno gel stent placement alone or combined with phacoemulsification between 1 January 2014 and 1 October 2015. Outcome measures included mean changes in intraocular pressure (IOP) and IOP-lowering medication count from medicated baseline at 1, 2, 3 (primary outcome) and 4 years (if available) postimplantation. Intraoperative complications, adverse events of special interest (AESIs) and secondary surgical interventions (SSIs) were recorded. RESULTS: The safety and effectiveness populations included 212 eyes (primary and secondary) and 174 eyes (primary), respectively. Mean IOP and medication decreased from 20.7 mmHg and 2.5 at baseline (n = 163 primary/first implanted eyes) to 13.9 mmHg and 1.1 medications (n = 76) at 3 years postimplantation, respectively. Mean changes from baseline in IOP (-5.6, -6.2 and -6.6 mmHg) and IOP-lowering medication count (-1.8, -1.6 and -1.4) were statistically significant at 1, 2 and 3 years postimplantation, respectively. Results appeared comparable when implantation was performed with (n = 76) or without (n = 98) phacoemulsification. In primary eyes with 4-year IOP and medication count data (n = 27), mean IOP was 14.0 mmHg on 1.3 medications at 4 years postimplantation. Fifteen (7.1%) eyes had intraoperative complications, 31 (14.6%) experienced 46 postoperative AESIs, and 26 (12.3%) required SSI. CONCLUSION: The gel stent effectively lowered IOP and IOP-lowering medication count over 3 years, with a predictable and acceptable safety profile, when implanted via the traditional ab-interno technique.

Case Report: Evaluating Intraocular Foreign Bodies After Corneal Perforation Using Swept Source Anterior Segment Optical Coherence Tomography.

SIGNIFICANCE: Use of anterior segment optical coherence tomography (OCT) is reported, exploring its advantages over other examination techniques. PURPOSE: The purpose of this study was to report a case in which anterior segment OCT was used to evaluate the presence of intraocular bodies after corneal perforation. CASE REPORT: A 33-year-old man was referred to our ophthalmology department after traumatic ocular injury. Swept-source anterior segment was carried out showing corneal perforation and anterior lens capsule rupture. CONCLUSIONS: Evaluating the integrity of posterior capsule and iris after traumatic ocular injury with corneal perforation using anterior segment OCT is a valuable tool to rule out the presence of intraocular foreign bodies without contact and without using radiating imaging techniques.

Dynamic Assessment of Light-Induced Vaulting Changes of Implantable Collamer Lens With Central Port by Swept-Source OCT: Pilot Study.

PURPOSE: To assess dynamic variations in vault induced by changes in brightness in eyes implanted with phakic collamer intraocular lens (pIOL) with central port for correction of myopia, defining new parameters of vaulting measurement. METHODS: We used a noninvasive Fourier-domain swept-source anterior-segment optical coherence tomography (AS-OCT) system to dynamically evaluate the shifts between the pIOL and anterior chamber structures under changing light conditions. For each eye assessed, we measured vault interval (VI), which we define based on central vault values in maximum mydriasis and in maximum miosis after light-induced changes in pupil diameter, and vault range (VR), which we define as the absolute difference between the VI values. RESULTS: The pilot study sample comprised 39 eyes (23 patients) previously implanted (mean 107 ± 156 days) with a pIOL. A significant difference in vault value was found when maximum and minimum pupil size was assessed under changing external light conditions (P < 0.001). The mean VR from scotopic (0.5 lux) to photopic (18,500 lux) light conditions was 167 ± 70 µm. CONCLUSIONS: Vault is continuously affected during movements of the pupil induced by external luminance. TRANSLATIONAL RELEVANCE: Quantifiable dynamic parameters VR and VI obtained with this AS-OCT device describe the position of the pIOL in the posterior chamber of the eye in a more accurate and real way than static vault measurements, and may contribute to improved understanding of the behavior of the pIOL in terms of safety.

A new technique for diode laser cyclophotocoagulation.

Destruction of the ciliary body, an option in glaucoma surgical treatment, can be performed using various methods. Laser energy, now the principle source for cyclodestruction, can be delivered in a transpupillar, transvitreal in conjunction with a vitrectomy and transscleral manner. The current technique for endocyclophotocoagulation requires of an endoscopic probe. We describe an accessible and inexpensive alternative. Gonioprism-assisted diode cyclophotocoagulation (GADC) with a peripheral corneal approach is a new surgical technique for pseudophakic and aphakic patients that uses a manual gonioprism, iris hooks, ophthalmic operating microscope, and an 810-nm laser diode probe. GADC is performed under topical and intracameral anesthesia, prior pupil dilation. First, 4 iris hooks are placed to expose the posterior chamber. The ciliary processes are viewed through a Swan-Jacob gonioprism and the diode laser probe is inserted through a peripheral corneal incision. The energy of the laser is set at 250 mW and the duration of the application to each process is variable, from 500 to 800 ms, until shrinkage and whitening occur. We apply this technique in approximately 360 degrees of the ciliary processes. Subconjunctival dexamethasone phosphate is administered at the end of the surgery prior subconjunctival injection of lidocaine. GADC has a relatively quick learning curve, allows direct visualization with less energy delivered to the ciliary processes and obviates the acquisition of a new endoscopic device.

Central toxic keratopathy: a clinical case series.

PURPOSE: To describe clinically, a case series of central toxic keratopathy (CTK), and contribute with one possible aetiology of this entity. METHODS: A retrospective observational case series, which included 12 eyes diagnosed with CTK after undergoing laser refractive surgery in situ keratomileusis (LASIK). RESULTS: From a total of 28 eyes that underwent LASIK in the same week, 12 develop CTK. The mean time of the diagnostic was 4 days after surgery. The resolution time had an interval between 1, 3 and 9 months, and an average of 4.6 months. The occurrence of CTK cases coincided with the change of the brand of surgical gloves, and no further cases were found after their replacement. CONCLUSIONS: The CTK clinical findings are well described, but with a yet unknown origin. It seems clear that it does not require specific treatment. It is possible that there might be a relationship between a substance of the gloves and CTK. Further studies are needed to know all the details of this process.

Intravitreal voriconazole for the treatment of Aspergillus chorioretinitis.

The aim of this article is to report a case of Aspergillus chorioretinitis successfully treated with intravitreal voriconazole based on an interventional case report. An immunodeficient patient, 34 years old, receiving systemic antifungal treatment for 1 month for invasive aspergillosis with necrotizing pneumonia and brain metastasis, who presented with blurred vision in his left eye. Visual acuity (VA) was 20/20 in his right eye, and 8/20 in his left eye. Ophthalmological examination showed a paramacular nodular yellowish chorioretinal lesion with intraretinal hemorrhages, in the absence of vitritis or anterior uveitis. The patient was treated with one dose of intravitreal voriconazole (100 µg/0.1 ml). One week after the intravitreal injection, the patient's VA was 10/20, the retinal lesions had diminished, and the hemorrhages had disappeared. At 3-month follow-up, his AV was 20/20 with a residual retinal scar. The significant and rapid improvement in this patient suggests that early injection of intravitreal voriconazole may be the first therapeutic option in Aspergillus chorioretinitis, obviating the need for vitrectomy.