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The confirmatory comment of Garcia-Teillard et al [...]

The biological history of Chlamydia trachomatis is intertwined with the evolution of the man. Infecting Elemental Bodies (EBs), having penetrated mucosal epithelial cells, wrap themselves in a cloak (ĸλαμις) of glycogen that ensures their obligatory intracellular survival and protects this differentiation into Reticulate Bodies (RBs) that feed on cellular ATP. Multiple chemokines and cytokines are involved under the direction of IL-6 in the florid phase and IL-17A in the scar phase. The WHO has successfully identified the SAFE strategy against trachoma (Surgery, Antibiotics, Facial cleansing, Environment) as the blueprint to eliminate the disease by 2020. Recently, interest has been increasingly focused on changing sexual attitudes in different areas of the world, leaving Musca sorbens, Scatophaga stercoraria, and stepsisters fairly blameless, but extolling the role of Chlamydia trachomatis in apparently “sterile” chronic prostatitis or conjunctivitis or, less frequently, in oropharyngitis and proctitis. The addition of an S (SAFE-S) standing for “sexual behavior” was then proposed to also attract the interest and attention not only of Ophthalmologists and Obstetricians/Gynecologists, Urologists/Andrologists, and the School Authorities for information on the prevention of sexually transmitted diseases, but also of Social Physicians and Pediatricians. This means that sexually transmitted infections should be screened in asymptomatic patients with risky sexual behavior or sexual contact with people diagnosed with a transmitted infection.

Among the symptoms of SARS-CoV-2, follicular conjunctivitis has become relevant. The conjunctiva acts as an open lymph node, reacting to the viral antigen that binds the epithelial cells, forming follicles of B cells with activated T cells and NK cells on its surface, which, in turn, talk to monocyte-derived inflammatory infected macrophages. Here, the NLRP3 inflammasome is a major driver in releasing pro-inflammatory factors such as IL-6 and caspase-1, leading to follicular conjunctivitis and bulbar congestion, even as isolated signs in the ‘asymptomatic’ patient.

Uveal melanoma (UM) is the most frequently found primary intraocular tumor, although it accounts for only 5% of all melanomas. Despite novel systemic therapies, patient survival has remained poor. Indeed, almost half of UM patients develop metastases from micro-metastases which were undetectable at diagnosis. Genetic analysis is crucial for metastatic risk prediction, as well as for patient management and follow-up. Several prognostic parameters have been explored, including tumor location, basal dimension and thickness, histopathologic cell type, vascular mimicry patterns, and infiltrating lymphocytes. Herein, the Authors review the available literature concerning cytogenetic prognostic markers and biochemical pathways correlated to UM metastasis development.

COVID-19 emerged in late 2019 in China and quickly spread across the globe, causing over 521 million cases of infection and 6.26 million deaths to date. After 2 years, numerous advances have been made. First of all, the preventive vaccine, which has been implemented in record time, is effective in more than 95% of cases. Additionally, in the diagnostic field, there are numerous molecular and antigenic diagnostic kits that are equipped with high sensitivity and specificity. Real Time-PCR-based assays for the detection of viral RNA are currently considered the gold-standard method for SARS-CoV-2 diagnosis and can be used efficiently on pooled nasopharyngeal, or oropharyngeal samples for widespread screening. Moreover, additional, and more advanced molecular methods such as droplet-digital PCR (ddPCR), clustered regularly interspaced short palindromic repeats (CRISPR) and next-generation sequencing (NGS), are currently under development to detect the SARS-CoV-2 RNA. However, as the number of subjects infected with SARS-CoV-2 continuously increases globally, health care systems are being placed under increased stress. Thus, the clinical laboratory plays an important role, helping to select especially asymptomatic individuals who are actively carrying the live replicating virus, with fast and non-invasive molecular technologies. Recent diagnostic strategies, other than molecular methods, have been adopted to either detect viral antigens, i.e., antigen-based immunoassays, or human anti-SARS-CoV-2 antibodies, i.e., antibody-based immunoassays, in nasal or oropharyngeal swabs, as well as in blood or saliva samples. However, the role of mucosal sIgAs, which are essential in the control of viruses entering the body through mucosal surfaces, remains to be elucidated, and in particular the role of the immune response in counteracting SARS-CoV-2 infection, primarily at the site(s) of virus entry that appears to be promising.

Retinitis pigmentosa (RP) is an inherited retinopathy. Nevertheless, non-genetic biological factors play a central role in its pathogenesis and progression, including inflammation, autophagy and oxidative stress. The retina is particularly affected by oxidative stress due to its high metabolic rate and oxygen consumption as well as photosensitizer molecules inside the photoreceptors being constantly subjected to light/oxidative stress, which induces accumulation of ROS in RPE, caused by damaged photoreceptor’s daily recycling. Oxidative DNA damage is a key regulator of microglial activation and photoreceptor degeneration in RP, as well as mutations in endogenous antioxidant pathways involved in DNA repair, oxidative stress protection and activation of antioxidant enzymes (MUTYH, CERKL and GLO1 genes, respectively). Moreover, exposure to oxidative stress alters the expression of micro-RNA (miRNAs) and of long non-codingRNA (lncRNAs), which might be implicated in RP etiopathogenesis and progression, modifying gene expression and cellular response to oxidative stress. The upregulation of the P2X7 receptor (P2X7R) also seems to be involved, causing pro-inflammatory cytokines and ROS release by macrophages and microglia, contributing to neuroinflammatory and neurodegenerative progression in RP. The multiple pathways analysed demonstrate that oxidative microglial activation may trigger the vicious cycle of non-resolved neuroinflammation and degeneration, suggesting that microglia may be a key therapy target of oxidative stress in RP.

Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD) and pathologic myopia (PM), both of which are frequently complicated by subfoveal choroidal neovascularization (CNV). Photodynamic therapy with verteporfin (PDT-V) is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985) has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1) total number of photodynamic treatments; and (2) change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype) received a higher number of photodynamic treatments than patients without it (GG wild-type genotype) (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively). Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively). The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of both anti-thrombophilic effects due to FXIII-A G185T variant and photo-thrombotic action of PDT-V toward CNV provides several clues about the rationale of this intriguing pharmacogenetic correlation. Further investigations are warranted to outline the appropriate paradigm for guiding PDT-V utilization in the course of the combined therapeutic protocol for neovascular macular degeneration.