Corneal stromal demarcation line after collagen cross-linking in corneal ectatic diseases: a review of the literature

Collagen cross-linking (CXL) is a relatively new conservative approach for progressive corneal ectasia, which is able to strengthen corneal tissue reforming new covalent bonds. Subjective and objective results following this method seem to be promising. In recent years, newer CXL protocols have been developed to perform more effective and less invasive procedures. The increasing diffusion of CXL in the corneal ectatic disease has increased the need to have actual indices regarding the efficacy of the treatment. Evaluation of demarcation line (DL), a transition zone between the cross-linked anterior corneal stroma and the untreated posterior corneal stroma, is considered a measurement of the depth of CXL treatment into the stroma. Some evidence in the literature emphasize that DL could be a measure of effectiveness of the CXL. On the contrary, some authors believe that the "the deeper, the better" principle is rather a simplistic approach for interpreting the clinical importance of the corneal stromal DL

Use of ozone-based eye drops. A series of cases in veterinary and human spontaneous ocular pathologies

Conjunctivitis, keratoconjunctivitis, and corneal ulcers are common eye disorders frequently diagnosed in both humans and animals, and are currently treated by topical administration of eye drops containing anti-inflammatory and antibacterial agents. The current molecules often lack efficacy because infections in hypoxic tissue contain methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa; thus, new products for the treatment of ocular pain and inflammation are needed. The use of ozone, a molecule stabilized for topical use as an ozonide, could be providential due to its anti-inflammatory and bactericidal activity in certain anterior segment pathologies, in addition to promoting tissue repair properties. Ozonated oils have the same properties as gaseous ozone and are well tolerated by tissues. In the present study the repair and regeneration effect of ozonated oil in liposomes plus hypromellose (Ozodrop®, FB Vision, Ascoli Piceno, Italy) instilled 3–4 times a day in external ocular spontaneous pathologies both in animals and humans are reported

Different graft thicknesses after Descemet stripping endothelial keratoplasty for bullous keratopathy in the two eyes of the same patient

Objective: To describe a very unique case of two Descemet stripping automated endothelial keratoplasty (DSAEK) surgeries performed in both eyes of the same patient with an extremely different graft thickness and overall corneal thickness but with the same corrected distance visual acuity (CDVA) 2 years after surgery. Case presentation: A 75-year-old woman with bilateral bullous keratopathy (BK) was submitted to DSAEK surgeries in both eyes, first in right and after 6 months in left eye. CDVA was 20/160 in the right eye and 20/63 in the left eye. Corneal thickness evaluated by anterior segment optical coherence tomography was 569 µm in the right eye and 560 µm in the left eye. The root mean square (RMS) was 2.1 in the right and left eyes. Endothelial cell densities were not detectable in both eyes. The estimated precut donor graft thickness from eye bank was 250 and 40 µm in the right and in the left graft, respectively. Two years after surgery CDVA was 20/25 in both eyes. Corneal thickness was 633 µm with a lenticule thickness of 206 µm in the right eye and 439 µm with a lenticule thickness of 48 µm in the left eye. The RMS was 1.7 in the right eye and 1.4 in the left eye. Endothelial cell density was 2.272 cells/mm2 in the right and 2.154 cells/mm2 in the left eye. Conclusion: DSAEK was safe and effective in the treatment of BK. In our report, the visual outcome resulted to be poorly related either to donor graft thickness or to postoperative corneal thickness

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Visuo-Acoustic Stimulation’s Role in Synaptic Plasticity: A Review of the Literature

Brain plasticity is the capacity of cerebral neurons to change, structurally and functionally, in response to experiences. This is an essential property underlying the maturation of sensory functions, learning and memory processes, and brain repair in response to the occurrence of diseases and trauma. In this field, the visual system emerges as a paradigmatic research model, both for basic research studies and for translational investigations. The auditory system remains capable of reorganizing itself in response to different auditory stimulations or sensory organ modification. Acoustic biofeedback training can be an effective way to train patients with the central scotoma, who have poor fixation stability and poor visual acuity, in order to bring fixation on an eccentrical and healthy area of the retina: a pseudofovea. This review article is focused on the cellular and molecular mechanisms underlying retinal sensitivity changes and visual and auditory system plasticity

Reply

Considering the oxygen diffusion barrier constituted by the epithelium, we reported differences in the corneal stromal demarcation line depth (rather than in CXL efficacy) secondary to the lower stromal penetration of riboflavin and to the ultraviolet-A light shielding effect of the intact corneal epithelium in transepithelial CXL protocols. As a consequence, we further agree that there is not a clear correlation between CXL effectiveness and corneal stromal demarcation line depth, and there is still much to understand in this direction

Visuo-acoustic stimulation’s role in synaptic plasticity: a review of the literature

Brain plasticity is the capacity of cerebral neurons to change, structurally and functionally, in response to experiences. This is an essential property underlying the maturation of sensory functions, learning and memory processes, and brain repair in response to the occurrence of diseases and trauma. In this field, the visual system emerges as a paradigmatic research model, both for basic research studies and for translational investigations. The auditory system remains capable of reorganizing itself in response to different auditory stimulations or sensory organ modification. Acoustic biofeedback training can be an effective way to train patients with the central scotoma, who have poor fixation stability and poor visual acuity, in order to bring fixation on an eccentrical and healthy area of the retina: a pseudofovea. This review article is focused on the cellular and molecular mechanisms underlying retinal sensitivity changes and visual and auditory system plasticity

Corneal stromal demarcation line after 4 protocols of corneal crosslinking in keratoconus determined with anterior segment optical coherence tomography

Purpose: To use anterior segment optical coherence tomography (AS-OCT) to compare corneal stromal demarcation line depth after 4 treatment protocols of corneal crosslinking (CXL). Setting: Eye Clinic, Sapienza University of Rome, Terracina (Latina), Italy. Design: Prospective case series. Methods: Patients with progressive keratoconus were delegated to one of the following CXL treatments: (1) conventional epithelium (epi)-off 3 mW/cm2according to the standard Dresden protocol (C-CXL group), (2) accelerated epi-off 10 mW/cm2(A-CXL group), (3) transepithelial epi-on 3 mW/cm2(TE-CXL group), or (4) transepithelial epi-on by iontophoresis 10 mW/cm2(I-CXL group). Two independent observers measured the corneal stromal demarcation line using AS-OCT. Results: The study comprised 70 patients (120 eyes, 30 eyes in each group). The corneal stromal demarcation line was identified on AS-OCT scans in 109 eyes (90.8%). One month after the treatment, the mean stromal demarcation line depth was 275.05 μm ± 41.83 (SD) in the C-CXL group, 279.35 ± 33.07 μm in the A-CXL group, 132.60 ± 22.14 μm in the TE-CXL group, and 235.40 ± 37.08 μm in the I-CXL group. The difference in stromal demarcation line depth was not statistically significant between the C-CXL and A-CXL group, but it was statistically significant (P <.05) between the epi-off and epi-on CXL groups and between the 2 epi-on groups, where the demarcation line was significantly deeper in the I-CXL group than in the TE-CXL group. Conclusion: The corneal stromal demarcation line was significantly deeper after epi-off 30-minute standard CXL treatment and after epi-off 9-minute accelerated CXL with high-intensity ultraviolet-A irradiation

Neural stem cells at the crossroads: MMPs may tell the way

Matrix metalloproteinases (MMP) constitute a family of more than 25 enzymes which process a large number of pericellular substrates. Even though initially reported to have an ability to degrade almost all of the extracellular components, MMP are now known to play roles which are not limited to the breakdown of extracellular barriers. In fact, MMPs regulate many biological processes, being involved not only in physiological events, but also in pathological processes. Strikingly, MMPs have been found to be involved in the physiology of the Central Nervous System (CNS), taking part and playing important roles in several processes such as repair and ontogeny, as well as in pathological conditions of the CNS. Initially considered to be a "static" structure, lacking regenerative capability, the CNS has been considered for a long time to be a system without renewal capabilities. Recently, the discovery of constant neural replacement has changed our way of considering the adult brain, and the finding of the existence of neural stem cells has opened the way to exciting and fascinating perspectives of the CNS. So, could MMPs, originally found during metamorphosis in tadpoles, and now amazingly identified in the CNS, have something to do in neuronal function? In this review we take into consideration the possible roles of two metalloproteinases, MMP-2 and MMP-9, also called gelatinases, in controlling several aspects of CNS organization, including the modulation of neural stem cell properties and the differentiation of their progeny, both under normal and pathophysiological conditions. © 2008 UBC Press

The Matrix Metalloproteinase Inhibitor Marimastat Promotes Neural Progenitor Cell Differentiation into Neurons by Gelatinase-Independent TIMP-2-Dependent Mechanisms

Metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs), produced in the brain by cells of non-neural and neural origin, including neural progenitors (NPs), are emerging as regulators of nervous system development and adult brain functions. In the present study, we explored whether MMP-2, MMP-9, and TIMP-2, abundantly produced in the brain, modulate NP developmental properties. We found that treatment of NPs, isolated from the murine fetal cerebral cortex or adult subventricular zone, with the clinically tested broad-spectrum MMP inhibitor Marimastat profoundly affected the NP differentiation fate. Marimastat treatment allowed for an enrichment of our cultures in neuronal cells, inducing NPs to generate higher percentage of neurons and a lower percentage of astrocytes, possibly affecting NP commitment. Consistently with its proneurogenic effect, Marimastat early downregulated the expression of Notch target genes, such as Hes1 and Hes5. MMP-2 and MMP-9 profiling on proliferating and differentiating NPs revealed that MMP-9 was not expressed under these conditions, whereas MMP-2 increased in the medium as pro-MMP-2 (72 kDa) during differentiation; its active form (62 kDa) was not detectable by gel zymography. MMP-2 silencing or administration of recombinant active MMP-2 demonstrated that MMP-2 does not affect NP neuronal differentiation, nor it is involved in the Marimastat proneurogenic effect. We also found that TIMP-2 is expressed in NPs and increases during late differentiation, mainly as a consequence of astrocyte generation. Endogenous TIMP-2 did not modulate NP neurogenic potential; however, the proneurogenic action of Marimastat was mediated by TIMP-2, as demonstrated by silencing experiments. In conclusion, our data exclude a major involvement of MMP-2 and MMP-9 in the regulation of basal NP differentiation, but highlight the ability of TIMP-2 to act as key effector of the proneurogenic response to an inducing stimulus such as Marimastat