HIV-associated progressive multifocal leukoencephalopathy. Current perspectives

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system, caused by the polyomavirus JC and occurring almost exclusively in the context of severe immune depression. AIDS represents the most common predisposing condition for PML development. Antiretroviral treatment has reduced PML incidence in HIV-infected subjects, but the disease remains a severe and life-threatening complication of AIDS, considering thus far the lack of an effective anti-JC virus (JCV) direct-acting antiviral drug. In the last decade, the use of monoclonal antibodies for treating immune-based diseases evidenced new predisposing conditions for PML development, promoting a renewed interest in PML pathogenesis. In this article, we review the current knowledge on JCV epidemiology and AIDS-associated PML incidence, JCV viral cycle, pathogenesis, and the interplay with HIV infection. We give an updated overview of diagnostic and prognostic tools available for PML diagnosis and describe past and current therapeutic approaches, including new strategies for PML cure

Malignant glaucoma following gonioscopy-assisted transluminal trabeculotomy: a case report

Background: To report a case of malignant glaucoma that developed after gonioscopy-assisted transluminal trabeculotomy (GATT). Case presentation: An 85-year-old male pseudophakic patient afected by pseudoexfoliative glaucoma (PEXG), unresponsive to medical glaucoma treatment, underwent uneventful GATT surgery. On the frst day after surgery, the eye showed a shallow central and peripheral anterior chamber (AC) with a raised intraocular pressure (IOP) measured at 55mmHg. Optical coherence tomography and ultrasound biomicroscopy confrmed the diagnosis of malignant glaucoma. Laser iridotomy, posterior capsulotomy and hyaloidotomy were performed, and the patient was treated with atropine sulphate 1%, maximum topical and systemic ocular hypotensive drugs with no improvement in the IOP. Subsequently, the patient underwent pars plana anterior vitrectomy, resulting in deepening of the AC with opening of the iridocorneal angle and decrease of the IOP. No further postoperative complications were recorded, and the IOP remained controlled 12months after surgery without antiglaucoma medications. Conclusions: Despite the minimally invasive profle of GATT, malignant glaucoma may develop after this procedure. Early recognition and prompt treatment are mandatory for preventing permanent visual loss

Iridocorneal endothelial syndrome in a patient with keratoconus. A case report

Background: To describe a case of a rare association of bilateral keratoconus and unilateral essential iris atrophy and to conduct a literature review of the current strategies of treatment of the corneal disease and glaucoma in patients with Iridocorneal Endothelial Syndrome (ICE). Case presentation: We report a rare association of bilateral keratoconus and unilateral essential iris atrophy in a 38-year-old man. Diagnosis of bilateral keratoconus was confirmed by corneal topography. Slit-lamp examination showed extensive iris atrophy with corectopia and policoria in one eye. Corneal specular microscopy revealed an abnormal endothelium morphology in the same eye with extensive peripheral anterior synechiae and closure of the drainage angle at gonioscopy. Intraocular pressure was 26 mmHg, despite maximal topical therapy. Optic disc examination showed severe glaucomatous cupping. Surgery by glaucoma drainage device implantation was performed. Conclusion: Essential iris atrophy is a rare clinical variant of ICE syndrome characterized by profound anatomical alterations of the anterior segment associated with corneal edema and secondary glaucoma. In these patients, selective keratoplasties have replaced penetrating keratoplasty to treat corneal decompensation and glaucoma drainage devices are preferred to conventional trabeculectomy for the treatment of secondary glaucoma

Reactivation of hepatitis B virus with immune-escape mutations after ocrelizumab treatment for multiple sclerosis

Ocrelizumab is an anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS) that is closely related to rituximab. We describe a case of hepatitis B virus (HBV) reactivation in an MS patient with resolved HBV infection receiving ocrelizumab. HBV reactivation was monitored with HBV-DNA and HBV surface antigen periodic assessment. Anti-HBV treatment with entecavir was started after HBV-DNA detection. Ocrelizumab can reactivate viral replication in patients with resolved HBV infection. HBV reactivation monitoring seems an effective and safe option for the management of these patients. More studies are needed to assess the optimal management of HBV reactivation in MS patients on ocrelizumab treatment

Subretinal injection of recombinant tissue plasminogen activator and gas tamponade to displace acute submacular haemorrhages secondary to age-related macular degeneration

Purpose: To analyse the efficacy of subretinal injection of recombinant tissue plasminogen activator (rtPA) and gas tamponade for the displacement of submacular haemorrhage (SMH). Methods: This single-centre, retrospective, case series included 25 consecutive patients (25 eyes) who underwent pars plana vitrectomy (PPV) with subretinal rtPA injection and 20% sulphur hexafluoride (SF6) tamponade. The primary outcome was SMH displacement rate, defined as the absence of subretinal blood within (complete) or outside (partial) 1500 μm centred on the fovea one month after PPV. Secondary outcomes were final best-corrected visual acuity (BCVA), central macular thickness (CMT), recurrence probability, number of anti-vascular endothelial growth factor (VEGF) injections after PPV, and intra- and post-operative complications. Results: Successful displacement was obtained in all 25 eyes (100%), with complete and partial displacement obtained in 15 (60%) and 10 (40%), respectively. BCVA significantly improved from 1.81±0.33 to 1.37±0.52 LogMar at 12 months from surgery (p = 0.001). The bivariate correlation analysis revealed that earlier the surgery had better visual prognosis at the end of the follow-up (p = 0.007). CMT significantly decreased from 922 ± 273.69 µm at baseline to 403.53 ± 314.64 µm at 12 months follow-up (p < 0.001). SMH recurrence was observed in two (8%) patients with a mean survival time of 11.6 ± 0.339 months and a cumulative survival probability of 88% at the end of follow-up. After PPV, the mean number of anti-VEGF injections was 3.00 ± 0.957 with no correlation with final visual acuity (p = 0.365). No intraoperative complications were recorded. Only one patient developed open funnel retinal detachment 40 days after primary PPV. Conclusion: PPV with rtPA subretinal injection and SF6 tamponade is a safe and effective technique in displacing acute SMHs secondary to neovascular AMD. It is recommended to perform within 14 days from the onset of the symptoms to achieve BCVA improvement at 12 months and proper imaging to plan future anti-VEG treatment

Low testosterone levels and high estradiol to testosterone ratio are associated with hyperinflammatory state and mortality in hospitalized men with COVID-19

Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19

JC virus-DNA detection is associated with CD8 fffector accumulation in peripheral blood of patients with multiple sclerosis under natalizumab treatment, independently from JC virus serostatus

Although natalizumab (anti-α4 integrin) represents an effective therapy for relapsing remitting multiple sclerosis (RRMS), it is associated with an increased risk of developing progressive multifocal leukoencephalopathy (PML), caused by the polyomavirus JC (JCV). The aim of this study was to explore natalizumab-induced phenotypic changes in peripheral blood T-lymphocytes and their relationship with JCV reactivation. Forty-four patients affected by RRMS were enrolled. Blood and urine samples were classified according to natalizumab infusion number: 0 (N0), 1-12 (N12), 13-24 (N24), 25-36 (N36), and over 36 (N > 36) infusions. JCV-DNA was detected in plasma and urine. T-lymphocyte phenotype was evaluated with flow cytometry. JCV serostatus was assessed. Ten healthy donors (HD), whose ages and sexes matched with the RRMS patients of the N0 group, were enrolled. CD8 effector (CD8 E) percentages were increased in natalizumab treated patients with detectable JCV-DNA in plasma or urine compared to JCV-DNA negative patients (JCV-) (p < 0.01 and p < 0.001, resp.). Patients with CD8 E percentages above 10.4% tended to show detectable JCV-DNA in plasma and/or urine (ROC curve p = 0.001). The CD8 E was increased when JCV-DNA was detectable in plasma or urine, independently from JCV serology, for N12 and N24 groups (p < 0.01). As long as PML can affect RRMS patients under natalizumab treatment with a negative JCV serology, the assessment of CD8 E could help in the evaluation of JCV reactivation

Minimally interface vitrectomy for rhegmatogenous retinal detachment with a single break in young patients

Purpose: This study evaluates a new surgical technique consisting of minimal vitreous removal under air (minimal interface vitrectomy; MIV) to reduce postoperative complications while preserving the ability to address surgical factors at the retinal break. Methods: This retrospective analysis examined the outcomes of minimal interface vitrectomies in consecutive cases, with a minimum 12-month follow-up period, of primary rhegmatogenous retinal detachment (RRD), recurrent RRD after pars plana vitrectomy (PPV), or failed surgery after primary scleral buckling surgery (SBS). Results: Twelve eyes of 12 patients with RRD underwent MIV. The total surgical duration was 190-300 s (mean, 245.25 s). Eight (66.7%) eyes were treated with cryotherapy, and 4 (33.3%) with endolaser to seal the retinal break. Successful, complete retinal reattachment was achieved in all eyes and maintained during follow-up. No intra- or postoperative complications occurred and no patients developed inflammation or cataract during follow-up. Conclusion and importance: We effectively removed traction and subretinal fluid and treated breaks with endolaser or cryotherapy by using a novel minimal interface vitrectomy technique in this selected population

Myxospermous seed-mucilage quantity correlates with environmental gradients indicative of water-deficit stress: Plantago species as a model

Abstract Aims Myxospermous seed mucilage is multifunctional and is often found in seeds (or achenes) of species occupying arid environments where the trait may influence seed-dispersal and -germination of seeds. The seed mucilage may also enhance soil-water retention, −hydraulic conductivity and -stability. However, the relationship between seed mucilage quantity, seed germination and seedling traits across environmental gradients which determine water-deficit stress has not yet been ascertained. Methods Therefore, we characterised and tested the relationship between seed mucilage quantity, water-deficit stress responses of seeds and seedlings of 36 accessions of four different Plantago species (P. albicans L., P. coronopus L., P. lagopus L. and P. anceolata L.). These were gathered from six regions across Europe, which presented environmental gradients (of rainfall and temperature), and varying soil qualities. Results Seed mucilage was significantly greater in seeds of accessions experiencing: highest summer temperatures; lowest summer precipitation; soils of the same warm dry regions which had greater capacity to retain water within narrow pore spaces. Under water-deficit stress, seeds with most mucilage exhibited a lower base water potential for germination, suffered least seedling mortality and exhibited the most successful seedling development. Conclusions The findings indicate that seed mucilage quantity appeared as an 'adaptive' trait and there is a relationship between seed-mucilage quantity, seed germination plus seedling survival and development under environmental conditions of highest water-deficit stress

Solar retinopathy: a new setting of red, green, and blue channels

Purpose: To introduce a new color imaging technique using improved settings of red, green, and blue channels for improved delineation of retinal damage in patients with solar retinopathy. Method: A retrospective case series of patients with poor vision secondary to solar retinopathy were analyzed. All patients underwent visual acuity, refraction, and dilated fundus examination. A spectral domain–optical coherence tomography of the macula and color fundus imaging using optimized red, green, and blue color setting was performed. Patients were reviewed over a 6-month period. The data were analyzed for statistical significance using an independent t test and a receiver operating characteristic curve. Results: In total, 20 eyes of 10 patients were included between 2009 and 2017. The mean age was 24.9 ± 18.1 years. Best corrected visual acuity at first consultation was 0.78 ± 0.11 and after 6 months was 0.83 ± 0.09. Spectral domain–optical coherence tomography demonstrated retinal abnormalities at the myoid zone, ellipsoid zone, and the outer segment of photoreceptors. Receiver operating characteristic curve analysis showed an improving effect (area under the curve = 0.62; 95% confidence interval = 0.42–0.79). The color channels parameters, which improve visualization of the lesions were found to be 67-0.98-255 for the R-guided setting, 19-0.63-121 for the B-guided setting, and 7-1.00-129 for the G-guided setting. The ideal red, green, and blue setting was in 24-0.82-229. Conclusion: The use of a new setting of red, green, and blue channels could improve the diagnosis and monitoring of solar retinopathy, hence improving patient care