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.

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.

Management of orofacial lesions with antimicrobial photodynamic therapy and photobiomodulation protocols in patients with COVID-19: A multicenter case series.

Several oral lesions related to COVID-19 have been described in the scientific literature. The COVID-19 pandemic highlighs importance of supportive protocols, which can reduce the inflammation and aid in tissue repair in severe cases. Photobiomodulation therapy (PBMT) alone or in combination with antimicrobial photodynamic therapy (aPDT) can be used to manage orofacial lesions in confirmed cases of COVID-19. Here, we sought to describe the clinical presentation and specificities of three cases in which aPDT and PBMT were used to manage orofacial lesions in patients with COVID-19. The laser protocols were effective with improvement of the orofacial lesions within a few days.

Phototherapies for COVID-19-associated opportunistic oral infections.

Opportunistic infections are widely described in patients with novel coronavirus disease 2019 (COVID-19); however, very few studies have addressed those affecting the oral cavity. Given the lack of information on the clinical presentations and the available treatment options, the present study aimed to show a case in which a combination of antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) was used for the management of two concomitant COVID-19-associated opportunistic oral infections (oral pseudomembranous candidiasis and recurrent herpes labialis). Within 7 days and without any systemic drug administration, all the lesions resolved completely, and the patient no longer reported oral pain or discomfort. According to the current case report and taking into consideration the significant gaps in the knowledge and understanding of COVID-19, this combination of phototherapy modalities seems to be a promising tool for managing viral and fungal opportunistic oral infections.

Recent Advances in Photosensitizers as Multifunctional Theranostic Agents for Imaging-Guided Photodynamic Therapy of Cancer.

In recent years tremendous effort has been invested in the field of cancer diagnosis and treatment with an overall goal of improving cancer management, therapeutic outcome, patient survival, and quality of life. Photodynamic Therapy (PDT), which works on the principle of light-induced activation of photosensitizers (PS) leading to Reactive Oxygen Species (ROS) mediated cancer cell killing has received increased attention as a promising alternative to overcome several limitations of conventional cancer therapies. Compared to conventional therapies, PDT offers the advantages of selectivity, minimal invasiveness, localized treatment, and spatio-temporal control which minimizes the overall therapeutic side effects and can be repeated as needed without interfering with other treatments and inducing treatment resistance. Overall PDT efficacy requires proper planning of various parameters like localization and concentration of PS at the tumor site, light dose, oxygen concentration and heterogeneity of the tumor microenvironment, which can be achieved with advanced imaging techniques. Consequently, there has been tremendous interest in the rationale design of PS formulations to exploit their theranostic potential to unleash the imperative contribution of medical imaging in the context of successful PDT outcomes. Further, recent advances in PS formulations as activatable phototheranostic agents have shown promising potential for finely controlled imaging-guided PDT due to their propensity to specifically turning on diagnostic signals simultaneously with photodynamic effects in response to the tumor-specific stimuli. In this review, we have summarized the recent progress in the development of PS-based multifunctional theranostic agents for biomedical applications in multimodal imaging combined with PDT. We also present the role of different imaging modalities; magnetic resonance, optical, nuclear, acoustic, and photoacoustic in improving the pre-and post-PDT effects. We anticipate that the information presented in this review will encourage future development and design of PSs for improved image-guided PDT for cancer treatment.

Photodynamic disinfection and its role in controlling infectious diseases.

Photodynamic therapy is witnessing a revival of its origins as a response to the rise of multi-drug resistant infections and the shortage of new classes of antibiotics. Photodynamic disinfection (PDDI) of microorganisms is making progresses in preclinical models and in clinical cases, and the perception of its role in the clinical armamentarium for the management of infectious diseases is changing. We review the positioning of PDDI from the perspective of its ability to respond to clinical needs. Emphasis is placed on the pipeline of photosensitizers that proved effective to inactivate biofilms, showed efficacy in animal models of infectious diseases or reached clinical trials. Novel opportunities resulting from the COVID-19 pandemic are briefly discussed. The molecular features of promising photosensitizers are emphasized and contrasted with those of photosensitizers used in the treatment of solid tumors. The development of photosensitizers has been accompanied by the fabrication of a variety of affordable and customizable light sources. We critically discuss the combination between photosensitizer and light source properties that may leverage PDDI and expand its applications to wider markets. The success of PDDI in the management of infectious diseases will ultimately depend on the efficacy of photosensitizers, affordability of the light sources, simplicity of the procedures, and availability of fast and efficient treatments.

Organic Photo-antimicrobials: Principles, Molecule Design, and Applications.

The emergence of multi-drug-resistant pathogens threatens the healthcare systems world-wide. Recent advances in phototherapy (PT) approaches mediated by photo-antimicrobials (PAMs) provide new opportunities for the current serious antibiotic resistance. During the PT treatment, reactive oxygen species or heat produced by PAMs would react with the cell membrane, consequently leaking cytoplasm components and effectively eradicating different pathogens like bacteria, fungi, viruses, and even parasites. This Perspective will concentrate on the development of different organic photo-antimicrobials (OPAMs) and their application as practical therapeutic agents into therapy for local infections, wound dressings, and removal of biofilms from medical devices. We also discuss how to design highly efficient OPAMs by modifying the chemical structure or conjugating with a targeting component. Moreover, this Perspective provides a discussion of the general challenges and direction for OPAMs and what further needs to be done. It is hoped that through this overview, OPAMs can prosper and will be more widely used for microbial infections in the future, especially at a time when the global COVID-19 epidemic is getting more serious.

Intranasal photobiomodulation therapy for COVID-19-related olfactory dysfunction: A Brazilian multicenter case series.

Olfactory dysfunction is commonly seen in COVID-19 patients; however, little is known about the pathophysiology and management. The present study aimed to report a series of cases in which three protocols of intranasal photobiomodulation therapy (PBMT) were used for COVID-19-related olfactory dysfunction. Irrespective of the PBMT protocol, olfaction recovery was noted in all cases but with varying degrees of improvement. Although intranasal PBMT seems to be a promising therapeutic modality, more research is needed to better define effectiveness.

The impact of delayed anti-vascular endothelial growth factor treatment for retinal diseases during the COVID-19 lockdown.

PURPOSE: To assess the clinical status of treatment-naive patients who had to delay 3-dose loading anti-VEGF (anti-vascular endothelial growth factor) injections during the COVID-19 lockdown, and to evaluate the effect of the delayed visual acuity treatment on spectral domain optical coherence tomography (SD-OCT) parameters. METHOD: A total of 55 eyes of 46 patients who were received in the study period participated in this retrospective study, including 28 patients (37 eyes) with diabetic macular edema (DME), 11 patients (11 eyes) with retinal vein occlusion (RVO), and 7 patients (7 eyes) with wet age-related macular degeneration (wet-AMD). The patients were diagnosed with DME, RVO, or wet-AMD in February 2020 and had planned 3-dose loading injections in March, April, and May 2020, but could not be injected due to the COVID-19 pandemic. RESULTS: From the patients' initial examination in February 2020, the mean best corrected visual acuity (BCVA) was 0.72 ± 59 logMAR. After the patients' lockdown visit in July 2020, the mean BCVA was 0.76 ± 64 logMAR. BCVA was stable in 11 eyes, decreased in 12 eyes, and increased in 14 eyes for patients with DME. BCVA was stable in 6, decreased in 3, and increased in 2 eyes for patients with RVO, and it was stable in 4 eyes and decreased in 3 eyes for patients with wet-AMD. CONCLUSION: We concluded that 6-month delay in treatment of DME patients with non-proliferative DRP had no adverse effect on the visual acuity. However, the loading dose in wet-AMD and RVO patients should be applied as soon as possible.

Photosensitizing Antivirals.

Antiviral action of various photosensitizers is already summarized in several comprehensive reviews, and various mechanisms have been proposed for it. However, a critical consideration of the matter of the area is complicated, since the exact mechanisms are very difficult to explore and clarify, and most publications are of an empirical and "phenomenological" nature, reporting a dependence of the antiviral action on illumination, or a correlation of activity with the photophysical properties of the substances. Of particular interest is substance-assisted photogeneration of highly reactive singlet oxygen (1O2). The damaging action of 1O2 on the lipids of the viral envelope can probably lead to a loss of the ability of the lipid bilayer of enveloped viruses to fuse with the lipid membrane of the host cell. Thus, lipid bilayer-affine 1O2 photosensitizers have prospects as broad-spectrum antivirals against enveloped viruses. In this short review, we want to point out the main types of antiviral photosensitizers with potential affinity to the lipid bilayer and summarize the data on new compounds over the past three years. Further understanding of the data in the field will spur a targeted search for substances with antiviral activity against enveloped viruses among photosensitizers able to bind to the lipid membranes.

A Membrane-Targeting Photosensitizer with Aggregation-Induced Emission Characteristics for Highly Efficient Photodynamic Combat of Human Coronaviruses.

COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, has resulted in global social and economic disruption, putting the world economy to the largest global recession since the Great Depression. To control the spread of COVID-19, cutting off the transmission route is a critical step. In this work, the efficient inactivation of human coronavirus with photodynamic therapy (PDT) by employing photosensitizers with aggregation-induced emission characteristics (DTTPB) is reported. DTTPB is designed to bear a hydrophilic head and two hydrophobic tails, mimicking the structure of phospholipids on biological membranes. DTTPB demonstrates a broad absorption band covering the whole visible light range and high molar absorptivity, as well as excellent reactive oxygen species sensitizing ability, making it an excellent candidate for PDT. Besides, DTTPB can target membrane structure, and bind to the envelope of human coronaviruses. Upon light irradiation, DTTPB demonstrates highly effective antiviral behavior: human coronavirus treated with DTTPB and white-light irradiation can be efficiently inactivated with complete loss of infectivity, as revealed by the significant decrease of virus RNA and proteins in host cells. Thus, DTTPB sensitized PDT can efficiently prevent the infection and the spread of human coronavirus, which provides a new avenue for photodynamic combating of COVID-19.

Photodynamic Therapy and Photobiomodulation on Oral Lesion in Patient with Coronavirus Disease 2019: A Case Report.

Objective: This article reports the case of a patient with oral manifestation of coronavirus disease 2019 (COVID-19) treated with photobiomodulation (PBM) and photodynamic therapy (PDT). Background: Some dermatological and oral mucosal lesions have recently been linked to severe acute respiratory syndrome coronavirus 2 infection. Methods: A 65-year-old female patient with a confirmed real-time reverse transcriptase-polymerase chain reaction diagnosis of COVID-19 presented with dry edematous lips, edema with mucosal desquamation, ulceration and blood crust on the inner aspect of the lips, gingival petechiae and erythematous and pseudomembranous lesions on the dorsum of the tongue. The treatment protocol was three sessions of antimicrobial PDT (aPDT) (660 nm diode laser + methylene blue) to the lips and tongue, every 24 h to control contamination, followed by PBM (low-power laser, 100 mW, 2 J/point) to the lips, tongue, and oral mucosa for additional four sessions every 24 h. Results: Therapy association promoted pain control and healing of oral mucosal lesions in 7 days of treatment. Conclusions: PBM and aPDT could be an interesting approach to manage COVID-19 patients.

Photobiomodulation and Antiviral Photodynamic Therapy in COVID-19 Management.

Coronavirus disease 2019 (COVID-19) has shocked the world by its spread and contagiousness. There is no approved vaccine and no proven treatment for this infection. Some potential treatments that have already been associated with antiviral and anti-inflammatory effects are under investigation. Photobiomodulation therapy (PBMT) is a photon-based therapy that uses light to mediate a variety of metabolic, analgesic, anti-inflammatory, and immunomodulatory effects. Antiviral photodynamic therapy (aPDT) is a branch of photodynamic therapy based on the reaction between a photosensitizing agent and a light source in the presence of oxygen, which can produce oxidative and free radical agents to damage the viral structures such as proteins and nucleic acids. This chapter aims to discuss the potential therapeutic benefit of PBMT and aPDT in the context of the novel coronavirus. Studies indicate that PBMT and aPDT could be useful in many viral and bacterial pulmonary complications like influenza, SARS-CoV, and MERS, but we found no direct study on SARS-CoV-2. With a combination of PBMT and aPDT, we may be able to combat COVID-19 with minimal interference with pharmaceutical agents. It might improve the efficacy of PBMT and aPDT by using monoclonal antibodies and preparing new photosensitizers at the nanoscale that target the lung tissue specifically. More animal and human studies would need to take place to reach an effective protocol. This chapter would encourage other scientists to work on this new platform.

Photobiomodulation therapy and antimicrobial photodynamic therapy for orofacial lesions in patients with COVID-19: A case series.

Oral lesions related to the novel Coronavirus Disease 2019 (COVID-19) have been increasingly described; however, clinical and epidemiological information is still scant. Although a diversity of therapeutic strategies for the management of these lesions are present in the literature, one can note a lack of standardization and doubtful effectiveness. Thus, the present study aimed to report a series of cases in which a combination of antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) was used for orofacial lesions in patients suffering from COVID-19. It was noted, in all cases, a marked improvement in tissue repair and pain relief within a few days; moreover, the patients recovered their orofacial functions satisfactorily. Based on the present series of cases and having in mind the conspicuous lack of information on the different aspects of COVID-19, the protocol which combined aPDT with PMBT seemed to be effective in the management of COVID-19-related orofacial lesions.

Impact of COVID-19 on keratoconus patients waiting for corneal cross linking.

PURPOSE: Royal College of Ophthalmologist recent guidance recommended delaying cross-linking services during the COVID-19 pandemic. This study investigates the effects of such delays in the delivery of cross-linking services in patients with keratoconus progression. METHODS: Retrospective observational study of 46 patients with keratoconus progression, whose cross-linking was delayed due to the COVID-19 pandemic. Demographic and clinical details were obtained from assessments on the day of listing, and subsequent review on the day of the procedure. Topographic indices included keratometry of the posterior and anterior corneal surface, maximum keratometry (Kmax), thinnest corneal thickness, ABCD progression and progression based on standard criteria recommendations (1.5 D Kmax & 20 microns thinning). RESULTS: A total of 46 eyes were analysed with an average time between being listed for CXL and having the procedure done was 182 ± 65 days. The delay due to COVID-19 was of 3 months. In this time period they had a significant worsening of all keratometric indices and lost almost one line of visual acuity (0.19 ± 0.19 to 0.26 ± 0.18 LogMAR, p: 0.03). Thirty two eyes (70%) demonstrated progression in accordance with the ABCD progression criteria, while 18 eyes (39%) showed either an increase in Kmax of more than 1.5D or a thinning in corneal thickness of at least 20 µm. CONCLUSIONS: The treatment delay for the keratoconus patients caused further progression and vision worsening. We recommend that corneal collagen crosslinking needs to be considered as a high priority intervention.