Ophthalmological Manifestations in Inflammatory Bowel Diseases: Keep an Eye on It.

BACKGROUND AND AIMS: Inflammatory bowel diseases (IBD) are multifactorial chronic inflammatory disorders affecting the gastrointestinal tract. However, a broad spectrum of extraintestinal manifestations (EIMs) is associated with IBD, affecting several organs and systems, such as the skin, musculoskeletal and hepatobiliary systems, and, not least, the eye. Approximately 10% of IBD patients can develop ocular EIMs (O-EIMs) with a higher prevalence in Crohn's disease (CD). Eye-redness, photophobia, pain, and blurred vision are the common symptoms, with a wide rate of severity and clinical impact on the quality of life. This narrative review aims to summarize the prevalence, pathogenesis, and current evidence-based management of O-EIMs, underlying the importance of a holistic approach and specialties collaboration for a prompt diagnosis and treatment. METHODS: PubMed was searched up to December 2023 to identify relevant studies investigating the pathogenesis, epidemiology, and treatment of O-EIMs in IBD patients. RESULTS: The mechanisms underlying O-EIMs are partially unknown, encompassing immune dysregulation, shared antigens between the eye and the gut, genetic predisposition, and systemic inflammation driven by high levels of interleukins and cytokines in IBD patients. The complexity of O-EIMs' pathogenesis reflects in the management of these conditions, varying from topical and systemic steroids to immunomodulatory molecules and biologic therapy, such as anti-tumor necrosis factor (TNF)-alpha. A multidisciplinary approach is the backbone of the management of O-EIMs.

Marketed Quinoa (Chenopodium quinoa Willd.) Seeds: A Mycotoxin-Free Matrix Contaminated by Mycotoxigenic Fungi.

A total of 25 marketed quinoa seed samples different for origin, farming system and packaging were analyzed for the presence of mycotoxigenic fungi (by isolation both on Potato Dextrose Agar and with the deep-freezing blotter method) and relative contamination by mycotoxins (by LC-MS/MS analysis). Fungal microorganisms, but not mycotoxins, were detected in all the samples, and 25 isolates representative of the mycobiota were obtained. Morphological and molecular characterization and, for some isolates, the in vitro mycotoxigenic profile, allowed the identification of 19 fungal species within five different genera: Alternaria, Aspergillus, Penicillium, Cladosporium and Fusarium. Among the identified species, Alternaria abundans, A. chartarum, A. arborescens, Cladosporium allicinum, C. parasubtilissimum, C. pseudocladosporioides, C. uwebraunianum, Aspergillus jensenii, A. tubingensis, Penicillium dipodomyis, P. verrucosum and P. citreosulfuratum were first reported on quinoa, and Alternaria infectoria and Fusarium oxysporum were first reported on quinoa seeds. The geographical origin, farming system and packaging were showed to affect the amount and type of the isolated fungal species, highlighting that the level of fungal presence and their related secondary metabolites is conditioned by different steps of the quinoa supply chain. However, despite the presence of mycotoxigenic fungi, the marketed quinoa seeds analyzed resulted in being free from mycotoxins.

Choroidal vascularity index in leptochoroid: A comparative analysis between reticular pseudodrusen and high myopia.

PURPOSE: To investigate the choroidal vascularity index (CVI) in patients affected by leptochoroid. METHODS: Three distinct age-matched cohorts were collected: patients with reticular pseudodrusen (RPD) secondary to age-related macular degeneration, patients with high-myopia, and healthy controls. CVI was calculated in the subfoveal 6000 µm diameter area. RESULTS: 54 eyes (54 patients) were included (18 eyes in each cohort). No statistical differences were disclosed in terms of age between controls, RPD patients (p = 0.062), and myopic patients (p = 0.070). Total choroidal area showed a different distribution among the 3 cohorts (p < 0.001), due to the reduction of luminal and stromal choroidal area in both RPD and myopic groups in comparison to controls (p < 0.001). Interestingly, CVI showed a different distribution between the 3 cohorts (p < 0.001). In detail, RPD group showed no changes in CVI in comparison to controls (p = 1.000), whereas the myopic group showed a higher CVI in comparison to both RPD group and controls (p < 0.001 in both analyses). CONCLUSIONS: Different changes of the choroidal vascular and stromal components characterize the leptochoroid secondary to RPD eyes and high-myopic eyes. The relative greater impairment of the vascular area in RPD eyes in comparison to myopic eyes could be at the basis of the lower development of RPD in patients with high myopia.

Choroidal vascularity index in eyes with central macular atrophy secondary to age-related macular degeneration and Stargardt disease.

PURPOSE: To compare macular atrophy (MA) secondary to age-related macular degeneration (AMD) and Stargardt disease (STGD) using the choroidal vascularity index (CVI). METHODS: In this multicentric retrospective study, two distinct cohorts were collected: patients with MA secondary to AMD and MA secondary to STGD. All patients were investigated using a multimodal imaging approach, including CVI in the subfoveal 1000 µm area. Of note, the CVI is not influenced by aging, which allows comparisons between different cohorts. RESULTS: Seventy eyes were included: 35 eyes of 35 patients (mean age 78 ± 7 years) in the AMD group and 35 eyes of 35 patients (mean age 41 ± 16 years, p < 0.001) in the STGD group. Choroidal thickness was significantly lower in the AMD group in comparison to the STGD group (151 ± 80 µm vs 353 ± 105 µm, p < 0.001). The total choroidal area (TCA) was significantly greater in the STGD group in comparison to the AMD group (1.734 ± 0.958 mm2 vs 0.538 ± 0.391 mm2, respectively, p < 0.001). Interestingly, the CVI was significantly lower in AMD patients in comparison to STGD patients (27.322 ± 15.320% vs 49.880 ± 7.217%, respectively, p < 0.001), and this difference was confirmed in the subgroup of patients over 50 years old. CONCLUSION: Our results corroborate the hypothesis that large choroidal vessels were impaired to a greater extent in AMD than in STGD. CVI may help in differentiating AMD from STGD in the presence of MA, better understanding of the pathogenesis, and monitoring of therapeutic response.

FLUID-BASED VISUAL PROGNOSTICATION IN TYPE 3 MACULAR NEOVASCULARIZATION-FLIP-3 STUDY.

PURPOSE: To analyze the effect of fluid on visual acuity in cases of Type 3 macular neovascularization. METHODS: This multicentric, retrospective cohort study included eyes with treatment-naïve Type 3 macular neovascularization. Analysis of fluid in different compartments was performed. Group A included eyes with isolated intraretinal fluid, whereas Group B included eyes with intraretinal fluid in conjunction with subretinal fluid and/or sub retinal pigment epithelial fluid. RESULTS: Eyes in Group A (31, 55.3%) had better best-corrected visual acuity of 20/50 snellen equivalent (0.42 ± 0.31 logarithm of the minimum angle of resolution) at baseline and 20/50 snellen equivalent (0.40 ± 0.28 logarithm of the minimum angle of resolution) at complete resolution compared with Group B with visual acuity of 20/80 snellen equivalent (0.64 ± 0.35 logarithm of the minimum angle of resolution) (P = 0.0181) at baseline and 20/100 snellen equivalent (0.70 ± 0.40 logarithm of the minimum angle of resolution) (P = 0.0021) at complete resolution. Subfoveal atrophy was more in Group B (82.6% 19/23) at complete resolution in comparison to Group A (16/31, 51.6%). Eyes in Group B needed more anti-vascular endothelial growth factor injections (10.3 ± 9.0) for complete resolution compared with Group A (5.7 ± 4.8). CONCLUSION: Intraretinal fluid may be associated with good visual acuity in Type 3 macular neovascularization in contrast to other forms of neovascular age related macular degeneration. Furthermore, intraretinal fluid in isolation may need fewer injections and could probably be associated with less subfoveal atrophy.

Three-year OCT predictive factors of disease recurrence in eyes with successfully treated myopic choroidal neovascularisation.

PURPOSE: To assess the relationship of demographics, clinical characteristics and structural optical coherence tomography (OCT) findings to disease recurrence in a cohort of patients with newly diagnosed myopic choroidal neovascularisation (CNV) METHODS: In this retrospective, longitudinal study, a total of 64 participants (64 eyes) with successfully treated myopic CNV had obtained resolution of exudation after treatment (study baseline) and with 3 years of regular follow-ups. Several baseline OCT qualitative features and quantitative measurements were assessed at baseline and included in the analysis. Main outcome measures included incidence of disease recurrence and HR for demographics, clinical characteristics and OCT risk factors. RESULTS: At month 36, 40 eyes (62.5%) developed disease recurrence (active CNV). Multivariate linear regression analysis revealed that final visual acuity (dependent variable) was associated with visual acuity at the first visit after complete resolution of exudation (p<0.0001), baseline size of patchy atrophy (p=0.010), baseline subfoveal choroidal thickness (p=0.008), baseline maximum CNV height and width (p=0.011 and p=0.003) and recurrence of CNV exudation (p=0.007). The following factors were associated with an increased risk of disease recurrence: size of patchy atrophy had an HR of 1.14 (95% CI 1.01 to 1.29; p=0.036); maximum CNV width had an HR of 1.02 (95% CI 1.01 to 1.04; p<0.0001). CONCLUSION: We identified OCT risk factors for the disease recurrence in eyes with successfully treated myopic CNV. Assuming that disease recurrence is a sight-threatening event, our findings may help in the identification of high-risk patients and eventually ameliorate their outcome.

Longitudinal assessment of type 3 macular neovascularization using 3D volume-rendering OCTA.

OBJECTIVE: To investigate the evolution of treatment-naive type 3 macular neovascularization (MNV) undergoing anti-vascular endothelial growth factor (VEGF) treatment through volume rendered three-dimensional (3D) optical coherence tomography angiography (OCTA). DESIGN: Retrospective observational study. PARTICIPANTS: Patients with type 3 MNV and age-related macular degeneration (AMD). METHODS: Included subjects had three loading injections of an anti-VEGF agent. The OCTA volume data at baseline and follow-up were processed with a previously published algorithm in order to obtain a volume-rendered representation of type 3 MNV. Progressive changes in type 3 lesions were analyzed via 3D OCTA volume rendering. RESULTS: A total of 14 treatment-naive eyes with type 3 MNV from 11 AMD patients (7 females) were included. At both baseline and follow-up visits, a type 3 MNV complex was identifiable. Each complex was composed of a mean number of 2.5 ± 0.7 vascular branches at baseline and 1.4 ± 0.6 at the follow-up visit (p < 0.0001). The mean changes in central macular thickness and visual acuity were significantly correlated with modifications in the number of type 3 MNV branches (ρ = -0.533, p = 0.049, and ρ = -0.581, and p = 0.040, respectively). CONCLUSIONS: This study demonstrated that type 3 lesions do not disappear completely after loading treatment, as indicated previously by histopathologic studies. Importantly, quantitative volume changes in type 3 lesions are directly associated with treatment response.

Choroidal Vascularity Index in Different Cohorts of Dry Age-Related Macular Degeneration.

Purpose: The purpose of this study was to investigate the choroidal luminal and interstitial stromal alterations using choroidal vascularity index (CVI) among different cohorts of dry age-related macular degeneration (dAMD) compared to healthy subjects. Methods: Four distinct cohorts were collected: three different cohorts of patients with dAMD (i.e. drusen, reticular pseudodrusen [RPD], and geographic atrophy [GA]) and an age-matched cohort of healthy subjects (controls). CVI (the ratio between the luminal choroidal area [LCA] and the total choroidal area [TCA]) was calculated in the subfoveal 1000 µm area. Results: One hundred twenty eyes (from 120 patients) were included (30 eyes in each cohort). The mean age was 76.6 ± 7.1 years. No statistical differences were disclosed in terms of age, axial length, and central macular thickness among study groups. TCA showed a different distribution among the four cohorts (P = 0.003), mainly due to the LCA changes (P = 0.001). Interestingly, CVI showed a different distribution among the four cohorts (P < 0.001). RPD showed a lower CVI in comparison to controls (P = 0.040), whereas GA showed a lower CVI in comparison to drusen, RPD, and controls (P = 0.001, P = 0.046, and P < 0.001, respectively). Conclusions: Different cohorts of dAMD are characterized by different impairments of the choroidal vascular and stromal components, reflecting different degrees of AMD severity. Translational Relevance: CVI provides insights for better understanding the pathogenesis of AMD.

The COVID-19 Pandemic Has Had Negative Effects on Baseline Clinical Presentation and Outcomes of Patients with Newly Diagnosed Treatment-Naïve Exudative AMD.

PURPOSE: To investigate whether the coronavirus disease 2019 (COVID-19) pandemic-associated postponement in care had effects on the baseline clinical presentation of patients with newly diagnosed treatment-naïve exudative neovascular age-related macular degeneration (AMD). METHODS: We included the first 50 consecutive patients referred within the COVID-19 pandemic with a diagnosis of treatment-naïve exudative neovascular AMD. Two groups of fifty consecutive patients with newly diagnosed neovascular exudative AMD presenting in 2018 and 2019 (control periods) were also included for comparisons. RESULTS: Baseline visual acuity was statistically worse in patients referred during the COVID-19 pandemic period (0.87 ± 0.51 logarithm of the minimum angle of resolution (LogMAR)) as compared with both the "2019" (0.67 ± 0.48 LogMAR, p = 0.001) and "2018" (0.69 ± 0.54 LogMAR, p = 0.012) control periods. Data on the visual function after a loading dose of anti-vascular endothelial growth factor (VEGF) was available in a subset of patients (43 subjects in 2020, 45 in 2019 and 46 in 2018, respectively). Mean ± SD best corrected visual acuity (BCVA) at the 1-month follow-up visit after the third anti-VEGF injection was still worse in patients referred during the COVID-19 pandemic (0.82 ± 0.66 LogMAR) as compared with both the "2019" (0.60 ± 0.45 LogMAR, p = 0.021) and "2018" (0.55 ± 0.53 LogMAR, p = 0.001) control periods. On structural optical coherence tomography (OCT), the maximum subretinal hyperreflective material (SHRM) height and width were significantly greater in the COVID-19 pandemic patients. CONCLUSIONS: We demonstrated that patients with newly diagnosed treatment-naïve exudative neovascular AMD referred during the COVID-19 pandemic had worse clinical characteristics at presentation and short-term visual outcomes.

Polypoidal choroidal vasculopathy in a patient with early-onset large colloid drusen.

PURPOSE: To report a case of a 46-year-old patient affected by polypoidal choroidal vasculopathy (PCV) in large colloid drusen (LCD) and to show how switching to intravitreal injection of aflibercept could be considered as a useful treatment of PCV not responsive to other anti-vascular endothelial growth factor (VEGF) injections. OBSERVATIONS: A 46-year-old woman was referred to our department with diagnosis of early-onset retinal drusen. Multimodal imaging confirmed the diagnosis of LCD in both eyes, complicated by suggestive PVC in the left eye. Due to the absence of anatomical improvement after 6 intravitreal injections of ranibizumab, the patient was switched and treated by a single injection of aflibercept, showing a complete anatomical and functional recovery. CONCLUSIONS AND IMPORTANCE: This case suggests progressive development of PCV as a possible late evolution of degenerating LCD. In case of exudative complication, intravitreal aflibercept injection could be considered as a useful treatment, especially in patients who are not responsive to others anti-VEGF injections.

Blockade of PD-1 decreases neutrophilic inflammation and lung damage in experimental COPD.

Chronic obstructive lung disease (COPD) and lung cancer are both caused by smoking and often occur as comorbidity. The programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) axis is an important canonic immunoregulatory pathway, and antibodies that specifically block PD-1 or PD-L1 have demonstrated efficacy as therapeutic agents for non-small cell lung cancer. The role of the PD-1/PD-L1 axis in the pathogenesis of COPD is unknown. Here, we analyzed the function of the PD-1/PD-L1 axis in preclinical COPD models and evaluated the concentrations of PD-1 and PD-L1 in human serum and bronchoalveolar lavage (BAL) fluids as biomarkers for COPD. Anti-PD-1 treatment decreased lung damage and neutrophilic inflammation in mice chronically exposed to cigarette smoke (CS) or nontypeable Haemophilus influenzae (NTHi). Ex vivo stimulated macrophages obtained from anti-PD-1-treated mice released reduced amounts of inflammatory cytokines. PD-L1 concentrations correlated positively with PD-1 concentrations in human serum and BAL fluids. Lung sections obtained from patients with COPD stained positive for PD-L1. Our data indicate that the PD-1/PD-L1 axis is involved in developing inflammation and tissue destruction in COPD. Inflammation-induced activation of the PD-1 pathway may contribute to disease progression.

IL-17C contributes to NTHi-induced inflammation and lung damage in experimental COPD and is present in sputum during acute exacerbations.

Neutrophilic inflammation results in loss of lung function in chronic obstructive pulmonary disease (COPD). Gram-negative bacteria, such as nontypeable Haemophilus influenzae (NTHi), trigger acute exacerbations of COPD (AECOPD) and contribute to chronic lung inflammation. The pro-inflammatory cytokine interleukin-17C (IL-17C) is expressed by airway epithelial cells and regulates neutrophilic chemotaxis. Here, we explored the function of IL-17C in NTHi- and cigarette smoke (CS)-induced models of COPD. Neutrophilic inflammation and tissue destruction were decreased in lungs of IL-17C-deficient mice (Il-17c-/-) chronically exposed to NTHi. Numbers of pulmonary neutrophils were decreased in Il-17c-/- mice after acute exposure to the combination of NTHi and CS. However, Il-17c-/- mice were not protected from CS-induced lung inflammation. In a preliminary patient study, we show that IL-17C is present in sputum samples obtained during AECOPD and associates with disease severity. Concentrations of IL-17C were significantly increased during advanced COPD (GOLD III/IV) compared to moderate COPD (GOLD I/II). Concentrations of IL-17A and IL-17E did not associate with disease severity. Our data suggest that IL-17C promotes harmful pulmonary inflammation triggered by bacteria in COPD.

OCT Risk Factors for 3-Year Development of Macular Complications in Eyes With "Resolved" Chronic Central Serous Chorioretinopathy.

PURPOSE: To assess the relationship between demographics, clinical characteristics, and structural optical coherence tomography (OCT) findings and the development of sight-threatening macular complications (choroidal neovascularization [CNV], large areas of retinal pigment epithelium [RPE] atrophy, and cystoid macular degeneration [CMD]) in a cohort of eyes with "resolved" chronic central serous chorioretinopathy (CSC) at study baseline. DESIGN: Retrospective cohort study. METHODS: In this study, a total of 71 eyes with "resolved" (absence of subretinal fluid) chronic CSC at baseline and 36 months of regular follow-up examinations were retrospectively enrolled. Structural OCT scans were reviewed. Baseline OCT qualitative features reflecting distress of the neuroretina, RPE, or choroid were assessed and included ellipsoid zone discontinuity, outer nuclear layer (ONL) thinning; presence of hyper-reflective intraretinal foci; dome-shaped pigment epithelium detachment (PED); hyper-reflective flat, irregular PED; hyporeflective flat, irregular PED; and inner choroidal attenuation. OCT images obtained at follow-up visits were also reviewed for development of macular complications (CNV, large areas of RPE atrophy [at least 250 µm in diameter], and CMD). Main outcome measurements included incidence of macular complications and hazard ratio (HR) for demographics, clinical characteristics, and OCT risk factors. RESULTS: At month 36, 20 eyes (28.2%) developed macular complications. Nine eyes (12.7%) displayed CNV, 9 eyes (12.7%) had large areas of RPE atrophy, and 2 eyes (2.8%) developed cystoid macular degeneration. The following factors were associated with an increased risk of development of CNV: intraretinal hyper-reflective foci had an HR of 11.58 (95% confidence interval [CI]: 1.10-37.24; P = .040); inner choroidal attenuation had an HR of 9.66 (95% CI: 1.07-22.34; P = .043); and the presence of macular complications in the fellow eye had an HR of 20.17 (95% CI: 1.34-39.41; P = .030). Factors associated with the development of RPE atrophy were also identified: ONL thinning had an HR of 13.47 (95% CI: 1.10-39.86; P = .042); dome-shaped PED had an HR of 21.40 (95% CI: 1.50-41.10; P = .031); and inner choroidal attenuation had an HR of 13.20 (95% CI: 1.07-39.32; P = .044). CONCLUSIONS: OCT risk factors were identified for the development of macular complications in eyes with chronic CSC. Findings may help in the identification of high-risk patients.

Choroidal luminal and stromal areas and choriocapillaris perfusion are characterised by a non-linear quadratic relation in healthy eyes.

PURPOSE: To assess the associations among different optical coherence tomography (OCT) structural and angiography quantitative metrics used to characterise the choroid in healthy subjects. METHODS: In this cross-sectional study, macular structural OCT and OCT angiography (OCTA) images were acquired from healthy subjects. The main outcome measures were: (i) choriocapillaris (CC) flow deficits percentage (FD%), (ii) choroidal luminal (LA) and stromal (SA) areas and (iii) choroidal vascularity index (CVI), which was calculated as the LA divided by the total choroidal area. These measurements were generated using previously published algorithms and were separately computed in the foveal and extrafoveal regions. RESULTS: Eighty-five eyes from 85 subjects (44 males, 41 females) were included in the analysis. Mean±SD age was 47.9±22.4 years (range: 19.0 to 85.0 years). Linear regression analysis displayed no significant associations between CC FD% and other parameters (LA, SA and CVI). Importantly, non-linear regression analysis showed that the relations of LA and SA to CC FD% were all best fitted by a quadratic function. Compared with the linear models, the use of the quadratic function allowed a relative increase in the R2 coefficients. No significant non-linear associations were found between CC FD% and CVI. CONCLUSION: Based on our models, changes in the luminal and stromal areas in the choroid lead to an initial increase in CC perfusion. Subsequently, further increases in LA and SA amounts are accompanied by a progressive increment in CC FD%.

TriPla Regimen: A new treatment approach for patients with neovascular age-related macular degeneration in the COVID-19 "era".

In the last months, a rapidly increasing number of people have been infected with severe acute respiratory syndrome coronavirus 2, the virus causing coronavirus disease 2019 (COVID-19). Due to the risk of cross-infections, the number of visits and injections was dramatically reduced in the last months, and the time between visits has been rescheduled from every 15 to 45 min, significantly impairing the total number of available visits. Although continuity of care has been allowed, a series of measures to diminish the risk of contamination need to be adopted until the end of this pandemic outbreak, which may persist until the development of an effective vaccine. For these reasons, we have introduced a new treatment regimen that is aimed at reducing the number of in-person visits and achieving continuity of treatment. This regimen is named "Triple and Plan" (TriPla). The main advantage of the TriPla regimen is to reduce the number of visits of patients in comparison to the pro re nata and treat and extend regimen. Using the TriPla regimen, the risk of contamination would be reduced. Furthermore, by reducing the number of scheduled visits, physicians could guarantee an adequate number of examinations for each patient, lengthening the interval between visits, and reducing the risk of cross-infections.

Rate of misdiagnosis and clinical usefulness of the correct diagnosis in exudative neovascular maculopathy secondary to AMD versus pachychoroid disease.

The aim of this study was to explore the relative prevalence and clinical differences between age-related macular degeneration (AMD) and pachychoroid disease in patients older than 50 years with newly diagnosed exudative neovascular maculopathy, and also assess the rate of misdiagnosis between these two disorders. In this retrospective observational study, we reviewed data from patients 50 years of age and older with newly diagnosed treatment-naïve exudative macular neovascularization (MNV) secondary to AMD or pachychoroid disease. Of the 139 patients (139 eyes) who fulfilled the inclusion criteria, 35 patients were graded as being affected by pachychoroid disease complicated by exudative MNV and 104 subjects had neovascular AMD. Therefore, prevalence of pachychoroid disease complicated by exudative MNV was 25.2% (confidence interval-CI 18.2-33.2%). Mean ± SD age was 67.0 ± 8.8 years in the pachychoroid disease group and 80.6 ± 6.6 years in the neovascular AMD group (P < 0.0001). At baseline, BCVA was better in patients with pachychoroid disease complicated by exudative MNV (0.4 ± 0.3 LogMAR vs. 0.7 ± 0.5 LogMAR, P = 0.003). At the 1-year follow-up visit, BCVA was still better in patients with pachychoroid-associated MNV (0.34 ± 0.32 LogMAR vs. 0.59 ± 0.52 LogMAR; P = 0.005). In our study cohort, 19 patients were graded to be affected by pachychoroid disease complicated by exudative MNV even though a diagnosis of neovascular AMD was erroneously reported in their medical records at baseline. In conclusion, pachychoroid disease is a frequent cause of exudative MNV in aged patients with a high rate of misdiagnosis. A correct diagnosis may be important as these two disorders differ in terms of clinical characteristics and prognosis.

Short-term outcomes of patients with neovascular exudative AMD: the effect of COVID-19 pandemic.

PURPOSE: To estimate the impact of delayed care during the coronavirus disease 2019 (COVID-19) pandemic on the outcomes of patients with neovascular age-related macular degeneration (AMD). METHODS: Consecutive patients with diagnosis of neovascular AMD were consecutively enrolled between March 9, 2020, and June 12, 2020, (during and immediately after the Italian COVID-19 quarantine). During the inclusion (or pandemic) visit (V0), patients received a complete ophthalmologic evaluation, including optical coherence tomography (OCT). Best-corrected visual acuity (BCVA) and OCT findings from the two preceding visits (V-1 and V-2) were compared with data at V0. RESULTS: One-hundred patients (112 eyes) were enrolled in this study. The time interval between following visits was 110.7 ± 37.5 days within V0 and V-1 and 80.8 ± 39.7 days within V-1 and V-2, respectively (P < 0.0001). BCVA was statistically worse at the V0 visit as compared with the immediately preceding (V-1) visit (0.50 ± 0.43 LogMAR and 0.45 ± 0.38 LogMAR at the V0 and V-1 visits, respectively; P = 0.046). On structural OCT, 91 out of 112 (81.2%) neovascular AMD eyes displayed the evidence of exudative disease activity at the V0 visit, while 77 (68.7%) eyes exhibited signs of exudation at the V-1 visit (P = 0.022). No differences in terms of BCVA and OCT findings were detected between the V-1 and V-2 visits. In multiple regression analysis, the difference in BCVA between V0 and V-1 visits was significantly associated with the interval time within these two visits (P = 0.026). CONCLUSION: The COVID-19 pandemic-related postponement in patient care proved to be significantly associated with worse short-term outcomes in these patients.

PLAC8 inhibits oral squamous cell carcinogenesis and epithelial-mesenchymal transition via the Wnt/ß-catenin and PI3K/Akt/GSK3ß signaling pathways.

Placenta-specific 8 (PLAC8) is closely associated with the proliferation, apoptosis and autophagy of several tumor cells. However, the expression and function of PLAC8 in oral squamous cell carcinoma (OSCC) remain unknown. Therefore, the present study investigated the function and mechanism of PLAC8 in OSCC. Reverse transcription-quantitative PCR and western blot analyses were performed to quantify the expression of PLAC8 in OSCC cell lines. The function of PLAC8 in OSCC was investigated via transfection, the Transwell and Cell Counting Kit-8 assays, immunofluorescence staining and western blotting. The results demonstrated that PLAC8 exspression was downregulated in OSCC cell lines. PLAC8 inhibited the cell proliferation in OSCC. In addition, PLAC8 restrained invasion and epithelial-mesenchymal transition of OSCC cells. Furthermore, ß-catenin helped to repress PLAC8 expression by regulating the Wnt/ß-catenin and PI3K/Akt/GSK3ß signaling pathways in OSCC cells. Collectively, the results of the present study suggest that PLAC8 acts as a tumor suppressor in OSCC by downregulating ß-catenin.

Impact of COVID-19 on outpatient visits and intravitreal treatments in a referral retina unit: let's be ready for a plausible "rebound effect".

PURPOSE: To quantify the shrinking in outpatient and intravitreal injections' volumes in a tertiary referral retina unit secondary to virus causing coronavirus disease 2019 (COVID-19). METHODS: In this retrospective cross-sectional study, we reviewed the charts of all patients who had a visit at a medical retina referral center during the Italian quarantine (from 9th of March 2020 to 3rd of May 2020). Number and characteristics of these data were compared with data from the same period in 2019 (from 9th of March 2019 to 3rd of May 2019). RESULTS: In the 2019 study period, there were 303 patients attending clinic (150 males, 153 females). In the 2020 study period, patients decreased to 75 (48 males, 27 females; P = 0.022 comparing gender prevalence between the two periods) with an overall reduction of 75.2%. Mean ± SD age was 71.4 ± 14.3 years (range 25-93 years) in the 2019 study period and 66.7 ± 13.1 years (range 32-91 years) in the 2020 study period (P = 0.005). The largest drop in outpatient volume was recorded in AMD patients (- 79.9%). Regarding the intravitreal treatments, there were 1252 injections in the 2019 period and 583 injections in the 2020 period (- 53.6% in injections). The drop in intravitreal treatments was larger in patients with posterior uveitis, retinal vein occlusion, and diabetes (- 85.7%, - 61.9%, and - 59.6%, respectively). CONCLUSION: The volume of outpatient visits and intravitreal injections declined during the COVID-19 quarantine. The short- and long-term impacts are that routine in-person visits and intravitreal injections are expected to increase after the quarantine and, even more, after the pandemic.