N-Glycosylation of the Ig Receptors Shapes the Antigen Reactivity in Chronic Lymphocytic Leukemia Subset #201.

Subset #201 is a clinically indolent subgroup of patients with chronic lymphocytic leukemia defined by the expression of stereotyped, mutated IGHV4-34/IGLV1-44 BCR Ig. Subset #201 is characterized by recurrent somatic hypermutations (SHMs) that frequently lead to the creation and/or disruption of N-glycosylation sites within the Ig H and L chain variable domains. To understand the relevance of this observation, using next-generation sequencing, we studied how SHM shapes the subclonal architecture of the BCR Ig repertoire in subset #201, particularly focusing on changes in N-glycosylation sites. Moreover, we profiled the Ag reactivity of the clonotypic BCR Ig expressed as rmAbs. We found that almost all analyzed cases from subset #201 carry SHMs potentially affecting N-glycosylation at the clonal and/or subclonal level and obtained evidence for N-glycan occupancy in SHM-induced novel N-glycosylation sites. These particular SHMs impact (auto)antigen recognition, as indicated by differences in Ag reactivity between the authentic rmAbs and germline revertants of SHMs introducing novel N-glycosylation sites in experiments entailing 1) flow cytometry for binding to viable cells, 2) immunohistochemistry against various human tissues, 3) ELISA against microbial Ags, and 4) protein microarrays testing reactivity against multiple autoantigens. On these grounds, N-glycosylation appears as relevant for the natural history of at least a fraction of Ig-mutated chronic lymphocytic leukemia. Moreover, subset #201 emerges as a paradigmatic case for the role of affinity maturation in the evolution of Ag reactivity of the clonotypic BCR Ig.

Peripapillary Retinoschisis as a Manifestation of Ocular Hypotony.

The aim of this case report was to present an unusual case of peripapillary retinoschisis (PPRS) associated with ocular hypotony after glaucoma surgery. It refers to a 78-year-old man with primary open-angle glaucoma who developed PPRS while hypotonous. Optical coherence tomography of the peripapillary and the macular area of the right eye revealed PPRS temporally and nasally to the optic disc, more prominent at the level of the outer nuclear layer and less so at the inner nuclear layer. The PPRS completely regressed after 1 month of treatment and restoration of intraocular pressure to normal levels. This case report highlights the fact that PPRS in glaucoma patients may present in the setting of ocular hypotony and appears to resolve when the hypotony is successfully managed. Hydrostatic pressure gradient across retinal vasculature that allows movement of fluid into the extracellular spaces is a potential mechanism for the development of PPRS in ocular hypotony.

Spontaneous Bilateral Hyphema in a Patient With Idiopathic Thrombocytopenic Purpura.

The aim of this case report is to present an unusual case of idiopathic thrombocytopenic purpura (ITP) with bilateral spontaneous hyphema. It refers to an 82-year-old Caucasian woman who presented with acute unilateral vision loss. The patient's medical history includes arterial hypertension, hypothyroidism, and uneventful bilateral cataract surgery. Bilateral anterior chamber hyphema was noted on gonioscopy, along with unilateral corneal edema. Hematology workup set the diagnosis of ITP. The cause of spontaneous bleeding in ITP patients is explained by the "second hit" hypothesis, suggesting that a secondary factor such as high blood pressure or minor trauma is necessary to cause rupture to a vessel's wall, which is already affected by the low platelet counts. The authors propose that, in this patient, the "second hit" was likely due to basement membrane alterations caused by arterial hypertension. The rarity of bilateral spontaneous hyphema cases and possible etiologies are emphasized.

Late-onset Relapse of Aqueous Misdirection after Pars Plana Vitrectomy: Case Report and Literature Review.

Aim: We report on an 88-year-old female patient who presented with a relapse in aqueous misdirection 15 years after being treated with pars plana vitrectomy (PPV) with hyaloidotomy-zonulectomy-iridotomy (HZI) for the same cause. Case description: A 73-year-old pseudophakic woman with a history of pseudoexfoliation underwent a trabeculectomy in the left eye in our institution because of uncontrolled intraocular pressure. Days after trabeculectomy, the patient developed aqueous misdirection and was treated with PPV combined with HZI. In the following years, the patient had regular follow-up appointments in our instruction, and she had normal intraocular pressures in the left eye without any treatment. A total of 15 years after the vitrectomy, the patient developed gradual swallowing in the anterior chamber and increased intraocular pressure. Neodymium (Nd): yttrium aluminum garnet (YAG) laser hyaloidotomy through the iridectomy opening was performed, the anterior chamber was immediately deepened, and the intraocular pressure was reduced to normal limits. The anterior chamber remained deep, and the intraocular pressure remained normal through the 36 months of follow-up. Conclusion: Relapse of aqueous misdirection may occur many years after vitrectomy, even when HZI is performed. An Nd: YAG- laser hyaloidotomy should be attempted before a second HZI is considered. Clinical relevance: A close and long-lasting follow-up of patients with aqueous misdirection is warranted, especially if the patients are treated not with complete PPV but by a limited disruption of the anterior hyaloid face along with HIZ. How to cite this article: Halkiadakis I, Tzimis V, Markopoulos I, et al. Late-onset Relapse of Aqueous Misdirection after Pars Plana Vitrectomy: Case Report and Literature Review. J Curr Glaucoma Pract 2023;17(1):49-51.

Evaluation of Corvis ST tonometer with the updated software in glaucoma practice.

AIM: To evaluate the agreement of biomechanically corrected intraocular pressure (b-IOP) and central corneal thickness (CCT) measurements obtained with the updated Corvis ST tonometer versus Goldmann applanation tonometry (GAT) and optical-based corneal pachymetry (OB-CCT) in controls, patients with ocular hypertension (OHT) and primary open angle glaucoma (POAG). Additionally, we examined the differences in corneal deformation parameters provided by the updated Corvis ST among the three groups. METHODS: For each participant, GAT IOP, OB-CCT and measurements with a Corvis ST with updated software were obtained. Bland-Altman analysis was used to assess the agreement between the two measurement methods. RESULTS: A consecutive series of 80 eyes from 80 participants (30 with POAG, 25 with OHT and 25 normal controls) were included in this prospective study. The mean GAT IOP of all eyes was 17.2±3.6 mm Hg, and the mean b-IOP was 15.9±3.7 mm Hg (Spearman's rho=0.767, P<0.001). The 95% limits of agreement (LoAs) ranged from -3.1 mm Hg to 5.5 mm Hg for GAT IOP and b-IOP. b-IOP was not correlated with OB-CCT (Spearman's rho=-0.13 P=0.917). Meanwhile there was a weak positive corelation between OB-CCT and GAT IOP-b-IOP difference (Spearman's rho=0.378, P=0.001). The mean OB-CCT was 549.5±36.4 µm, and the Corvis-CCT was 556.1±41.5 µm (Spearman's rho=0.900, P<0.001). No statistically significant difference in the new indices provided by the updated Corvis ST was detected among the three groups. Compared with control eyes, POAG eyes had a significantly reduced applanation time 2 after adjusting for OB-CCT and GAT IOP (P=0.048). CONCLUSION: Corvis b-IOP and CCT correlate well with GAT IOP and OB-CCT. b-IOP is not affected by CCT, which might be an advantage, especially in thick or thin corneas. Corvis ST yields shorter applanation time 2 measurements in patients with POAG, which might reflect altered corneal viscoelasticity.

Ligand-Receptor Interactions and Drug Design.

In silico rational drug design is one of the major pylons in the drug discovery process. Drugs usually act on specific targets such as proteins, DNA, and lipid bilayers. Thus, molecular docking is an essential part of the rational drug design process. Molecular docking uses specific algorithms and scoring functions to reveal the strength of the interaction of the ligand to its target. AutoDock is a molecular docking suite that offers a variety of algorithms to tackle specific problems. These algorithms include Monte Carlo Simulated Annealing (SA), a Genetic Algorithm (GA), and a hybrid local search GA, also known as the Lamarckian Genetic Algorithm (LGA). This chapter aims to acquaint the reader with the docking process using AutoDockTools (GUI of AutoDock). Furthermore, herein is described the docking process of calf thymus DNA with three metal complexes, as a potential metallo-therapeutics as also the docking process of the plant flavonoid quercetin to the antiapoptotic protein BcL-xL.

Assessment of Corneal Epithelium Thickness in Glaucomatous Patients Undergoing Medical Treatment.

PRECIS: Patients with glaucoma have reduced and irregular corneal epithelial thickness (CET) even if they do not report symptoms of dry eyes. The reduction of corneal epithelium affects equally the superior and inferior areas of the cornea. PURPOSE: To evaluate CET parameters by means of anterior segment optical coherence tomography in glaucomatous patients undergoing medical treatment and compare them with CET parameters of controls. METHODS: This was a cross-sectional study of 62 patients with primary open-angle or pseudoexfoliative glaucoma (study group) and 62 age-matched controls. Fourier-domain optical coherence tomography (RTVue) with a corneal adaptor module was used in the present study. Τhe pachymetry scan pattern was used to map the cornea and the software generated corneal thickness parameters were recorded. Simple comparisons between groups were performed and the correlations of CET parameters with parameters associated with medication use (treatment duration, number of medications and number of instillations) were assessed. RESULTS: Mean age of the patients was 68±11.9 years in the glaucoma group and 65.5±8.5, years in the control group (P=0.17). Median number of instillations of medication was 2 (range, 1 to 6) for the glaucoma group. Central corneal thickness was 537.6±33.3 in the glaucoma group and 550.8±33.7 in the control group, respectively (P=0.028). The central CET was 48.8.±3.7 µm in the glaucoma group and 53.5±3.7 µm in the control group (P<0.001). Similarly, the average superior (2 to 7 mm) CET and the average inferior (2 to 7 mm) CET were almost equally reduced in the glaucoma group (45±4 vs. 49.6±3.3 µm, P<0.001 and 49±3.9 vs 53.5±3.7, P<0.001, respectively). No CET parameter was correlated with any of the treatment parameters. CONCLUSIONS: Patients treated for glaucoma have uniformly reduced corneal epithelial thickness.

User generated content for enhanced professional productions: a mobile application for content contributors and a study on the factors influencing their satisfaction and loyalty.

Motivated by a combination of social media, technological evolution, as well as new habits and preferences of TV content consumers, there is an increasing demand for enhancement of professional productions with user generated content. Studies have explored the potential and feasibility of this approach, indicating that footage from non-professionals can be effectively used to enrich the viewing experience. However, an important concern is whether such efforts are appealing to potential contributors, and what can actually impact their satisfaction and loyalty. Aiming to investigate these factors, this paper presents a mobile application for content contributors and a study involving 38 attendees of live events, using the application in the field. The events were hosted in two different countries, and transmitted by two well-known broadcasters. The results suggest that age, gender, technological expertise, and overall sharing attitude do not affect the satisfaction and loyalty of contributors. The differentiating factors, however, are the filming confidence and expertise of contributors, as well as the Wi-Fi/4G connectivity on-site. Implications of these findings are discussed and recommendations for similar endeavors are provided.

A Corneal Perforation Related to Beauveria Bassiana and Post-Penetrating Keratoplasty Management Discussion.

Fungal keratitis is an infection that is insidious and frequently misdiagnosed. Those with chronic eye surface conditions, contact lenses, systemic immunosuppression, and diabetes have been the most frequently affected with fungal keratitis. An 84-year-old male patient with a history of bilateral penetrating keratoplasty (PK) for keratoconus presented with pain and decreased visual acuity on his left eye. A corneal perforation was found, which was treated immediately with a full-thickness corneal transplant. The specimen was sent for bacterial and fungal cultures. Topical corticosteroids were prescribed postoperatively. Beauveria bassiana was isolated from the corneal scrapings. The postoperative treatment was modified by reducing the dose of corticosteroid and adding topical natamycin together with systemic posaconazole. No recurrence occurred in the transplant four months postoperatively under topical dexamethasone 0.1% b.i.d.  This is the first case of keratitis and perforation in a previously transplanted cornea. Due to the rarity of the infection, there are no clear guidelines for postoperative prophylaxis in B. bassiana infection. Either the continuation of corticosteroids or the switch to another immunosuppressive therapy and selecting the appropriate antifungal regimen posed a significant therapeutic dilemma.

Structural and functional impairment of the retina and optic nerve in Alzheimer's disease.

PURPOSE: The purpose of this study was to evaluate the macular and retinal nerve fiber layer (RNFL) thickness, and the electrical activity of the macula in patients with Alzheimer's disease (AD). MATERIAL AND METHODS: 30 patients with AD and 30 age and sex matched healthy controls were studied. The thickness and the electrical activity of the macula were evaluated by means of optical coherence tomography (OCT) and multifocal-electroretinogram (mf-ERG). RESULTS: Visual acuity, as well as visual fields and colour vision testing of all patients were normal. However, the mean foveal thickness was 148.50 µm (vs. 171.50 µm in the control group, p=0.001) and the RNFL thickness was 104.5 µm in the superior area (vs 123 µm in the control group, p < 0.0001) and 116.5 µm in the inferior area (vs. 138 µm in the control group, p < 0.0001) around the optic nerve. The mean P1 response density amplitude of the foveal area was 146.50 nV/deg2 (vs. 293 nV/deg2 in the control group, p < 0.0001) and the perifoveal area was 56.60 nV/deg2 (vs. 81.50 nv/deg2 in the control group, p < 0.001). CONCLUSION: Our study showed that in patients with AD, even without visual failure there was a decrease in macular and RNFL thickness, as well as a decrease of the electrical activity of the macula.

Optical coherence tomography and multifocal electroretinogram study in human immunodeficiency virus-positive children without infectious retinitis.

BACKGROUND: The aim was to evaluate the macular structure and function in children with human immunodeficiency virus (HIV) disease without cytomegalovirus retinitis or visual symptoms. METHODS: Thirty-eight eyes of 19 HIV-positive children (Group A) were examined. Group B included 20 (40 eyes) age- and sex-matched control subjects. Each individual underwent a complete ophthalmic examination, optical coherence tomography (OCT) scan and multifocal electroretinogram (mfERG) recording. RESULTS: In all patients, visual acuity and colour vision testing were normal. The mean foveal thickness in groups A and B was 190.28 ± 26.58 (SD) µm and 169.47 ± 10.17 µm, respectively (p = 0.0002). In Group A, the mean retinal response density of the fovea (area 1) was 19.87 ± 10.16 nV/deg(2) and the latency was 38.56 ± 1.18 ms. In the parafoveal area (area 2), the mean retinal response density was 10.82 ± 2.34 nV/deg(2) and the mean latency was 36.52 ± 1.73 ms. In the perifoveal area (area 3), the mean retinal response density was 10.83 ± 0.90 nV/deg(2) and the mean latency was 36.36 ± 1.90 ms. In Group B, the mean retinal response density of area 1 was 22.02 ± 0.9 nV/deg(2) and the mean latency was 32.56 ± 1.25 ms. In area 2, the mean retinal response density was 12.23 ± 0.55 nV/deg(2) and the mean latency was 30.84 ± 1.22 ms. Finally, in the perifoveal area (area 3), the mean retinal response density was 12.74 ± 0.44 nV/deg(2) and the mean latency was 29.7 ± 11.09 ms. The differences in amplitude and latency were statistically significant. CONCLUSION: Increased foveal thickening and significant decrease of the electrical activity of areas 1, 2 and 3 were found in HIV-positive children. These findings suggested some subclinical dysfunction of the photoreceptors and the inner retinal layers of the fovea in HIV-positive children with normal vision and without ocular disease.

Anatomical and functional impairment of the retina and optic nerve in patients with anorexia nervosa without vision loss.

AIM: The aim of this cross-sectional study is to evaluate the macular and retinal nerve fibre layer (RNFL) thickness, as well as the electrical activity of the macula in female patients suffering from anorexia nervosa (AN) without visual failure. MATERIAL AND METHODS: 13 female patients (26 eyes) suffering from AN without visual failure and 20 age and sex-matched healthy female controls (40 eyes) were studied. For the measurement of the macula thickness and the electrical activity of the macula, the optical coherence tomography (OCT) and the multifocal electroretinogram were used respectively. RESULTS: The visual acuity, as well as the visual fields, the colour vision testing and the dark adaptation test of all patients were normal. However, the mean foveal thickness was 140.04 µm (vs 150.85 in the control group, p=0.005), and the RNFL thickness was limited to 116.42 µm in the superior area (vs 123.15 in the control group, p=0.372) and 121.08 µm in the inferior area (vs 137.6 in the control group, p<0.001) around the optic nerve. Also, the mean P1 response density amplitude of the foveal area was 159.04 nV/deg(2) (vs 292.43 in the control group, p<0.0001), and the perifoveal area was 79.04 nV/deg(2) (vs 82.63 in the control group, p=0.118). CONCLUSION: The present study shows that in patients with AN, even without visual failure there is a decrease in macular and RNFL thickness, as well as a decrease in the electrical activity of the macula.

Morphologic changes and functional retinal impairment in patients with Parkinson disease without visual loss.

PURPOSE: To investigate the anatomic and electrophysiologic changes of the macula and the optic nerve in patients with Parkinson disease (PD) without visual impairment. METHODS: Thirty-two eyes of 16 patients with PD (group A) without visual impairment were tested. Visual acuity was 20/20 or better and visual fields as well as color vision testing results were normal. Also, no retinal lesions were assessed. Patients in group B (40 eyes of 20 patients) were age- and sex-matched control subjects. All study participants underwent a comprehensive ophthalmic examination, multifocal electroretinogram (mfERG) recording, and optical coherence tomography (OCT) scan. Thickness of retinal nerve fiber layer (RNFL) along a 3.4-mm-diameter circle centered on the optic nerve head was evaluated using third-generation OCT. RESULTS: The mean P1-response density amplitude of ring 1 of mfERG was 136.69 nV/deg2 in patients with PD and 294 nV/deg2 in control subjects and the difference was highly significant. On the contrary, these values in ring 2 and 3 did not differ statistically between controls and patients with PD. The mean inferior and temporal RNFL thickness was significantly lower in patients with PD than in control subjects (p<0.0001 and p=0.0045, respectively). CONCLUSIONS: In patients with PD with normal vision, we found a decrease in the electrical activity of the fovea as well as in the thickness of the RNFL. Multifocal electroretinogram and OCT scan objectively detect early subclinical PD-associated visual functional impairment.