Morphovascular changes after anti-VEGF intravitreal injection for a choroidal neovascularization secondary to COVID-19 infection in a pediatric patient.

Choroidal neovascularization (CNV) is a common pathologic lesion that occurs in various chorioretinopathy. Although the incidence of CNV is quite rare in children and adolescents, these lesions have a severe impact on visual acuity and quality of life over patients' lifetime. The management of CNV in pediatric patients is challenging, clear guidelines are limited due to a lack of randomized clinical trials. However, the more promising option is the use of vascular endothelial growth factor (VEGF) inhibitors. We reported a case of recurrent idiopathic choroidal neovascularization in a healthy pediatric patient after COVID 19 infection. Optical coherence tomography angiofraphy (OCTA) showed, in a non invasive way, a choroidal neovascularization at the posterior pole including macula and superior temporal arcade in the right eye, while the left eye was unaffected. In order to inactivate the neovascularization, intravitreal injections of anti-VEGF (Lucentis-Ranibizumab 0.3 mL) were performed in the right eye. Six months after the injections BCVA of the right eye was improved from 0.7 logMAR to 0.2 logMAR. OCT-A examination did not detect any signs of attivation of the preexistent neovascularization. It is reasonable to assert that Anti-VEGF could be the main treatment in case of choroidal neovascularization in young patients after COVID 19 infection due to the high chorioretinal level of VEGF-A described in these diseases.

Early effects of inactivated (CoronaVac) SARS-CoV-2 vaccine on retrobulbar vascular blood flow and retinal vascular density.

AIMS: We aimed to investigate the early effects of inactivated SARS-CoV-2 vaccine on retrobulbar vascular blood flow and retinal vascular density in healthy subjects. METHODS: Thirty-four eyes of 34 healthy volunteers who received the CoronaVac (Sinovac Life Sciences, China) were included in this prospective study. Resistive index (RI), pulsatility index (PI) and peak systolic velocity (PSV) of the ophthalmic artery (OA), central retinal artery (CRA), and the temporal and nasal posterior ciliary arteries (PCA) were evaluated with color Doppler ultrasonography (CDUS) before vaccination, at the 2nd and 4th weeks after vaccination. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vessel density (VD), foveal avascular zone (FAZ), and choriocapillaris blood flow (CCF) measurements were made using optical coherence tomography angiography (OCTA). RESULTS: When compared to the pre-vaccination values, there was no significant change in OA-PSV, temporal-nasal PCA-PSV, CRA-EDV, temporal-nasal PCA-EDV at 2nd and 4th weeks after vaccination. However statistically significant reductions were found in the OA-RI, OA-PI, CRA-RI, CRA-PI, temporal-nasal PCA-RI, temporal-nasal PCA-PI values, CRA-PSV at post-vaccination 2nd week (p<0.05 for all). While there was sustained reduction in OA-RI, OA-PI, CRA-PSV, and nasal PCA-RI values at 4th week after vaccination, the change in CRA-RI, CRA-PI, temporal PCA-RI, temporal-nasal PCA-PI values were not significant compared to pre-vaccination values. There was no statistically significant difference in the SCP-VD, DCP-VD, FAZ and CCF measurements. CONCLUSIONS: Our findings demonstrating that CoronaVac vaccine did not affect retinal vascular density in the early period, but it caused alterations in the retrobulbar blood flow.

Macular optical coherence tomography angiography analysis in diabetes mellitus patients with a history of Covid-19.

PURPOSE: There is evidence of decreased vessel density in optical coherence tomography angiography (OCTA) after Covid-19. We aimed to investigate whether the outcome of retinal vasculopathy would be worse if patients with diabetes mellitus (DM) were infected with coronavirus using OCTA to assess retinal vessels. METHODS: One eye of each subject was included in the study. Diabetic patients without retinopathy and non-diabetic controls were divided into four groups according to their Covid-19 history: group 1=DM(-)Covid-19(-); group 2=DM(+)Covid-19(-); group 3=DM(-)Covid-19(+); and group 4=DM(+)Covid-19(+). All Covid-19 patients were not hospitalised. Macular OCTA scans were performed in a 6 × 6 mm area. RESULTS: Diabetes had no effect on the area of the foveal avascular zone (FAZ), but Covid-19 caused an increase in FAZ area. Diabetes and Covid-19 had an effect on both the superficial capillary plexus (SCP) and the deep capillary plexus (DCP) in the fovea. Eta squared (ƞ2) is a measure of effect size. The effect size of Covid-19 (ƞ2=0.180) was found to be greater than that of diabetes (ƞ2=0.158) on the SCP, whereas the effect size of diabetes (ƞ2=0.159) was found to be greater than that of Covid-19 (ƞ2=0.091) on the DCP. CONCLUSIONS: The percentage of vessel density was lower in the fovea and the FAZ area was enlarged in the diabetic patients who recovered from Covid-19. In diabetic patients Covid-19 may lead to deterioration of vascular metrics.

Retinal microvascular changes in patients recovered from COVID-19 compared to healthy controls: A meta-analysis.

PURPOSE: To investigate changes in retinal microcirculation in patients recovered from COVID-19 infection compared to healthy controls, using optical coherence tomography-angiography. METHODS: Meta-analysis of eligible studies comparing retinal microcirculation between patients recovered from COVID-19 infection and healthy controls up to 7th of September 2022 was performed, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. The following search algorithm was used: (COVID-19 OR coronavirus) AND (retina OR optical coherence tomography OR optical coherence tomography angiography OR vessel density OR foveal avascular zone). Standardized Mean Difference (SMD) with 95% confidence interval (CI) was calculated to compare continuous variables. Revman 5.3 was used for the analysis. RESULTS: 12 studies were included in our analysis. Foveal avascular zone (FAZ) area was larger in patients recovered from COVID-19 infection compared to healthy controls, while there was no statistically significant difference in FAZ perimeter between the two groups. The foveal, parafoveal and whole image vessel density in the superficial capillary plexus showed no significant difference between the two groups. The foveal, parafoveal and whole image vessel density in the deep capillary plexus was statistically lower in patients recovered from COVID-19 compared to healthy controls. CONCLUSION: FAZ area was enlarged and foveal, parafoveal and whole image vessel density in deep capillary plexus were reduced in patients recovered from COVID-19 infection compared to healthy controls, suggesting that COVID-19 infection may induce long-term retinal microvascular changes in patients recovered from the virus infection.

Recent Advances in Green Metallic Nanoparticles for Enhanced Drug Delivery in Photodynamic Therapy: A Therapeutic Approach.

Globally, cancer is one of the leading causes of death among men and women, it is characterized by the unregulated proliferation of tumor cells. Some of the common risk factors associated with cancer development include the consistent exposure of body cells to carcinogenic agents such as alcohol, tobacco, toxins, gamma rays and alpha particles. Besides the above-mentioned risk factors, conventional therapies such as radiotherapy, and chemotherapy have also been linked to the development of cancer. Over the past decade, tremendous efforts have been invested in the synthesis of eco-friendly green metallic nanoparticles (NPs), and their medical application. Comparatively, metallic NPs have greater advantages over conventional therapies. Additionally, metallic NPs can be functionalized with different targeting moieties e.g., liposomes, antibodies, folic acid, transferrin, and carbohydrates. Herein, we review and discuss the synthesis, and therapeutic potential of green synthesized metallic NPs for enhanced cancer photodynamic therapy (PDT). Finally, the advantages of green hybridized activatable NPs over conventional photosensitizers (PSs) and the future perspectives of nanotechnology in cancer research are discussed in the review. Furthermore, we anticipate that the insights offered in this review will inspire the design and development of green nano-formulations for enhanced image-guided PDT in cancer treatment.

The effect of various types of COVID-19 vaccines on the retinal microvasculature.

PURPOSE: To detect the effect of various types of COVID-19 vaccine on macular and optic disc microvasculature. METHOD: One hundred subjects receiving various types of COVID-19 vaccine (AstraZeneca, Sinopharm, Sinovac, Pfizer, and Moderna) were included in this study. A complete ophthalmic examination was done which included best-corrected visual acuity measurement, slit-lamp biomicroscopy, intraocular pressure measurement with Goldmann applanation tonometry, and fundus examination. Optical coherence tomography angiography (OCT-A) was done before and 1 week after receiving the vaccine. Superficial and deep macular capillary densities were measured in the form of the whole image, fovea, parafoveal, and perifoveal capillary density. Optic disc vessel density in the form of the whole disc, inside disc, and peripapillary were also measured. RESULTS: The superficial macular vessel densities, (whole image, fovea, parafoveal, and perifoveal) showed statistically non-significant changes with P-values (0.269, 0.167, 0.346, and 0.476) respectively. Also, the deep macular vessel densities showed statistically non-significant changes with P-values (0.491, 0.096, 0.724, and 0.386) for the whole image, fovea, parafoveal, and perifoveal respectively. Moreover, RPC (radial peripapillary capillary) density showed no significant changes either (the whole disc, inside disc, or peripapillary) with P-values (0.807, 0.141, 0.883) respectively. CONCLUSION: Various types of COVID-19 vaccines had no statistically significant effects on macular or optic disc microvasculature.

Evaluation of acute effects of pulmonary involvement and hypoxia on retina and choroid in coronavirus disease 2019: An optic coherence tomography study.

PURPOSE: We investigated the acute subclinical choroidal and retinal changes caused by Coronavirus Disease 2019 (COVID-19) in patients with and without pulmonary involvement, using spectral domain optic coherence tomography. METHODS: This prospective case-control study included COVID-19 patients: 50 with pulmonary involvement and 118 with non-pulmonary involvement. All patients were examined 1 month after recovering from COVID-19. The changes were followed using optic coherence tomography parameters such as choroidal and macular thickness and retinal nerve fibre layer and ganglion cell complex measurements. RESULTS: All choroidal thicknesses in the pulmonary involvement group were lower than in the non-pulmonary involvement group and the subfoveal choroidal thickness differed significantly (p=0.036). Although there were no significant differences between the central and average macular thicknesses in the two groups, they were slightly thicker in the pulmonary involvement group (p=0.152 and p=0.180, respectively). A significant decrease was detected in the pulmonary involvement group in all ganglion cell complex segments, except for the outer nasal inferior segment (p<0.05). In addition, a thinning tendency was observed in all retinal nerve fibre layer quadrants in the pulmonary involvement group compared to the non-pulmonary involvement group. CONCLUSION: In COVID-19 patients with pulmonary involvement, subclinical choroidal and retinal changes may occur due to hypoxia and ischemia in the acute period. These patients may be predisposed to ischemic retinal and optic nerve diseases in the future. Therefore, COVID-19 patients with pulmonary involvement should be followed for ophthalmological diseases.

Investigation of changes in retinal vascular parameters and choroidal vascular index values during the early recovery period of COVID-19: The COVID-OCTA study.

BACKGROUND: COVID-19 effects microvasculature in many tissues. This study investigated whether the choroidal structure is also affected. METHODS: This cross-sectional study included 80 patients with COVID-19 and the same number of age- and gender-matched healthy individuals. All participants' right eye measurements were examined. Optical coherence tomography angiography (OCTA) was used for imaging. Otherwise, two independent researchers used the Choroidal vascular index (CVI) for choroidal parameters calculation. RESULTS: Superior and deep flow values were lower in the COVID-19 group than in the control group, and vascular density (VD) values were lower in all regions in this group. Except for the superior mean VD, there was no statistically significant difference (p = 0.003). However, the COVID-19 group had significantly lower subfoveal choroidal thickness (SFChT) measurements than the control group (p = 0.001). In addition, no significant difference was observed between the groups in evaluating mean CVI values (p>0.05). CONCLUSION: Noninvasive diagnostic tools such as OCTA and EDI-OCT can be used to monitor early changes in diseases affecting microvessels, such as from COVID-19.

Awareness comportment and attitude of dental practitioners for photodynamic therapy during COVID-19 pandemic: a global survey.

OBJECTIVE: The aim of the study is to evaluate the awareness, comportment and attitude/perception of dentists regarding the use of photodynamic (PD) therapy before and during COVID-19 pandemic around the globe. SUBJECTS AND METHODS: An online survey was performed by sending out an online questionnaire comprising 21 questions among dental practitioners working in four different countries: Saudi Arabia, Pakistan, Malaysia and United Kingdom. The survey evaluated dental practitioners' level of awareness about the PD therapy, comportment and attitude for its implication and prevalence in daily clinical practice. For statistical significance the Chi-square analysis with Spearman Correlation coefficient was conducted to assess the sub-groups and correlating the factors with the level of awareness of the dental practitioners. RESULTS: A total of 1,219 dental practitioners from four different countries (Saudi Arabia, Pakistan, Malaysia and United Kingdom) responded to the questionnaire. The median age of the respondents was 37, 34, 36 and 39 respectively. The majority of dental practitioners demonstrated to have an acceptable level of awareness regarding PD therapy. Nearly 76%, 74%, 79% and 80% of the individuals from Saudi Arabia, Pakistan, Malaysia and United Kingdom respectively were aware of the role/mechanism of action of the PD therapy. Moreover, in preponderance, practitioners were confident that the effect of PD therapy will not be reduced in patients infected with COVID-19. The majority of dental practitioners were convinced that successful dental treatment due to PD therapy is linked majorly with therapies done in relation to four major dental specialties: prosthodontics, endodontic, restorative dentistry and periodontology. Approximately more than 90% of the dentists were sure that the rate of COVID-19 transmission can be reduced by using PD therapy in oral treatments. The dental practitioners from Saudi Arabia (91%), Pakistan (82%), Malaysia (83%) and United Kingdom (82%) were contented to learn about PD therapy for its use in clinical practice. Nearly more than 95% of the practitioners from the four countries were keen to attend the lectures/hands-on workshops regarding PD therapy to enhance their skills and knowledge. More than 80% of dentists do not refuse the peripheral role of PD therapy with their patients. CONCLUSIONS: The respondents from the four countries displayed passable level of awareness regarding basic information of PD therapy and its clinical implication in dental specialty. Nevertheless, there is a need to develop awareness regarding the use of PD therapy among dental practitioners during their undergraduate program. Furthermore, lectures and hands-on workshops should be arranged to train dental practitioners in order to enhance their skills for its solicitation in clinical practice. It is perceived by the dentists in the four countries that the use of PD therapy can effectively reduce COVID-19 rate of transmission.

Translational feasibility and efficacy of nasal photodynamic disinfection of SARS-CoV-2.

The lack of therapeutic options to fight Covid-19 has contributed to the current global pandemic. Despite the emergence of effective vaccines, development of broad-spectrum antiviral treatment remains a significant challenge, in which antimicrobial photodynamic therapy (aPDT) may play a role, especially at early stages of infection. aPDT of the nares with methylene blue (MB) and non-thermal light has been successfully utilized to inactivate both bacterial and viral pathogens in the perioperative setting. Here, we investigated the effect of MB-aPDT to inactivate human betacoronavirus OC43 and SARS-CoV-2 in vitro and in a proof-of-principle COVID-19 clinical trial to test, in a variety of settings, the practicality, technical feasibility, and short-term efficacy of the method. aPDT yielded inactivation of up to 6-Logs in vitro, as measured by RT-qPCR and infectivity assay. From a photo-physics perspective, the in vitro results suggest that the response is not dependent on the virus itself, motivating potential use of aPDT for local destruction of SARS-CoV-2 and its variants. In the clinical trial we observed variable effects on viral RNA in nasal-swab samples as assessed by RT-qPCR attributed to aPDT-induced RNA fragmentation causing falsely-elevated counts. However, the viral infectivity in clinical nares swabs was reduced in 90% of samples and undetectable in 70% of samples. This is the first demonstration based on quantitative clinical viral infectivity measurements that MB-aPDT is a safe, easily delivered and effective front-line technique that can reduce local SARS-CoV-2 viral load.

Molecular Modeling and Simulation Analysis of Antimicrobial Photodynamic Therapy Potential for Control of COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enter the host cells by binding the viral surface spike glycoprotein (SG) to angiotensin-converting enzyme 2. Since antiviral photodynamic therapy (aPDT) has been described as a new method for inhibiting viral infections, it is important to evaluate whether it can be used as a photoactivated disinfectant to control COVID-19. In this in silico study, SARS-CoV-2-SG was selected as a novel target for curcumin as a photosensitizer during aPDT to exploit its physicochemical properties, molecular modeling, hierarchical nature of protein structure, and functional analysis using several bioinformatics tools and biological databases. The results of a detailed computational investigation revealed that SARS-CoV-2-SG is most similar to 6VXX_A, with 100% query cover and identity. The predicted structure of SARS-CoV-2-SG displayed that it is a protein with a positive charge and random coil dominates other secondary structures located outside the viral cell. The protein-protein interaction network showed that SARS-CoV-2-SG interacted with ten potential interacting partners. In addition, primary screening of binding modes through molecular docking showed that curcumin desires to bind and interact with residues of SARS-CoV-2-SG as the main site to enhance the yield of aPDT. Overall, the computer simulation reveals that SARS-CoV-2-SG can be a suitable target site for interaction with curcumin during aPDT.

UV 254 nm is more efficient than UV 222 nm in inactivating SARS-CoV-2 present in human saliva.

Ultraviolet (UV) light can inactivate SARS-CoV-2. However, the practicality of UV light is limited by the carcinogenic potential of mercury vapor-based UV lamps. Recent advances in the development of krypton chlorine (KrCl) excimer lamps hold promise, as these emit a shorter peak wavelength (222 nm), which is highly absorbed by the skin's stratum corneum and can filter out higher wavelengths. In this sense, UV 222 nm irradiation for the inactivation of virus particles in the air and surfaces is a potentially safer option as a germicidal technology. However, these same physical properties make it harder to reach microbes present in complex solutions, such as saliva, a critical source of SARS-CoV-2 transmission. We provide the first evaluation for using a commercial filtered KrCl excimer light source to inactivate SARS-CoV-2 in saliva spread on a surface. A conventional germicidal lamp (UV 254 nm) was also evaluated under the same condition. Using plaque-forming units (PFU) and Median Tissue Culture Infectious Dose (TCID50) per milliliter we found that 99.99% viral clearance (LD99.99) was obtained with 106.3 mJ/cm2 of UV 222 nm for virus in DMEM and 2417 mJ/cm2 for virus in saliva. Additionally, our results showed that the UV 254 nm had a greater capacity to inactivate the virus in both vehicles. Effective (after discounting light absorption) LD99.99 of UV 222 nm on the virus in saliva was ∼30 times higher than the value obtained with virus in saline solution (PBS), we speculated that saliva might be protecting the virus from surface irradiation in ways other than just by intensity attenuation of UV 222 nm. Due to differences between UV 222/254 nm capacities to interact and be absorbed by molecules in complex solutions, a higher dose of 222 nm will be necessary to reduce viral load in surfaces with contaminated saliva.

Retrobulbar ocular blood flow and choroidal vascular changes in patients recovering from COVID-19 infection.

BACKGROUND: To evaluate the effects of COVID-19 infection on the ocular vascular structure including choroidal thickness and retrobulbar blood flow values in comparison with healthy subjects. METHODS: Ninety eyes of 90 patients were included in this study. Participants were divided into Group 1 (n = 30) with mild COVID-19 infection, Group 2 (n = 31) with moderate disease, and Group 3 with age- and sex-matched healthy subjects (n = 29). Choroidal thickness was measured at the subfoveal area and at 500-µm intervals nasal and temporal to the fovea up to a distance of 1500 µm, using the enhanced depth imaging (EDI) technique of spectral coherence tomography (SD-OCT). The peak systolic velocity (PSV), end diastolic velocity (EDV), resistive index (RI), and pulsatility index (PI) values of the central retinal artery (CRA) and ophthalmic artery (OA) were evaluated with color Doppler ultrasonography (CDU). RESULTS: The choroidal thickness was significantly thinner in Group 1 and Group 2 than in Group 3 at all measurement points (p <0.001). This difference was not present between Group 1 and Group 2 who had COVID-19 disease of different severity (p>0.05).Among the retrobulbar blood flow parameters, OA PSV value was significantly lower in Group 1 and Group 2 compared to Group 3 (p = 0.025, p = 0.016, respectively). However, the CRA PSV and EDV and OA EDV values, and the CRA and OA PI and RI values were not statistically different between the groups (p> 0.05). CONCLUSION: COVID-19 infection may predispose patients to ocular vascular pathologies by affecting both choroidal and retrobulbar blood flow.

Retinal microvascular morphology versus COVID-19: What to anticipate?

BACKGROUND: To investigate retinal microvascular morphological changes in previously COVID-19 infected patients using optical coherence tomography angiography (OCTA), and compare the findings to age- and gender-matched healthy subjects. METHODS: In this cross-sectional study, OCTA findings (6.0 × 6.0 mm scan size and scan quality index ≥7/10) from previously COVID-19 infected patients (group 1, 32 patients, 64 eyes) with ≥1 month of complete recovery were compared to healthy subjects (group 2, 33 subjects, 66 eyes) with no history of COVID-19 infection. A positive real-time reverse transcription-polymerase chain reaction test on a naso-pharyngeal swab sample confirmed the diagnosis. The AngioVueAnalytics, RTVue-XR 2017.1.0.155 software measured and recorded OCTA parameters. RESULTS: Group 1 had significantly lower superficial capillary plexus vessel densities in all foveal regions than group 2 (P<0.05). Foveal deep capillary plexus vessel density in group 1 was also significantly lower than in group 2 (P=0.009); however, no significant differences were found in other regions (P>0.05). All foveal avascular zone (FAZ) parameters were higher in group 1 than in group 2, with significant differences in FAZ area (P=0.019) and foveal vessel density 300 µm area around FAZ (P=0.035), but not FAZ perimeter (P=0.054). The outer retina and choriocapillaris flows were significantly lower in group 1 than in group 2 (P<0.05). CONCLUSIONS: Prior COVID-19 infection seems to be associated with significant changes in retinal microvascular density, as well as FAZ and flow parameters, which may be attributed to different pathogenic mechanisms that lead to SARS-CoV-2 infection, such as thrombotic microangiopathy and angiotensin-converting enzyme 2 disruption.

Tuning riboflavin derivatives for photodynamic inactivation of pathogens.

The development of effective pathogen reduction strategies is required due to the rise in antibiotic-resistant bacteria and zoonotic viral pandemics. Photodynamic inactivation (PDI) of bacteria and viruses is a potent reduction strategy that bypasses typical resistance mechanisms. Naturally occurring riboflavin has been widely used in PDI applications due to efficient light-induced reactive oxygen species (ROS) release. By rational design of its core structure to alter (photo)physical properties, we obtained derivatives capable of outperforming riboflavin's visible light-induced PDI against E. coli and a SARS-CoV-2 surrogate, revealing functional group dependency for each pathogen. Bacterial PDI was influenced mainly by guanidino substitution, whereas viral PDI increased through bromination of the flavin. These observations were related to enhanced uptake and ROS-specific nucleic acid cleavage mechanisms. Trends in the derivatives' toxicity towards human fibroblast cells were also investigated to assess viable therapeutic derivatives and help guide further design of PDI agents to combat pathogenic organisms.

aPDT for oral decontamination of hospitalized patients with COVID 19.

Emerging variants of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) may have an impact on the virus's transmissibility and pathogenicity and an increased risk of reinfection. Antimicrobial photodynamic therapy (aPDT) is a promising technique to decontaminate the oral cavity to minimize and inactivate microorganisms' load. This article reports through a case series, a proposal for efficient oral decontamination for hospitalized patients with COVID 19 using aPDT. Samples of oral tissues were obtained after aPDT and analyzed using two methods of RT-qPCR to elucidate qualitative and quantitative viral profiles of SARS-CoV-2 RNA in the oral cavity. There was a reduction of viral load in the oral cavity immediately or one hour after the use of aPDT. This method could be a good option to decontaminate the oral cavity to minimize and inactivate microorganism load.