Effect of Corneal Allogenic Intrastromal Ring Segment (CAIRS) Implantation Surgery in Patients With Keratoconus According to Prior Corneal Cross-linking Status.

PURPOSE: To compare the effects of corneal allogenic intrastromal ring segment (CAIRS) implantation on topographical measurements and visual outcomes of patients with keratoconus with and without corneal cross-linking (CXL) prior to the time of implantation. METHODS: Sixty-seven eyes with corneal allograft intrastromal ring segment implantation (KeraNatural; Lions VisionGift) due to advanced keratoconus were included in the study. Thirty-seven eyes had no CXL and 30 eyes had had CXL before being referred to the authors. The changes in spherical equivalent (SE), uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), steep keratometry (K1), flat keratometry (K2), mean keratometry (Kmean), maximum keratometry (Kmax), and thinnest pachymetry were retrospectively analyzed 6 months after the implantation. RESULTS: The median age was 29 years in the CXL group and 24.0 years in the non-CXL group (P > .05), respectively. All topographical and visual parameters before implantation were similar in both groups (P > .05 for all parameters). At 6 months, CDVA, K1, and Kmean showed higher improvement in the non-CXL group than the CXL group (P = .030, .018, and .039, respectively). CONCLUSIONS: CAIRS surgery has a flattening effect on both the corneas with and without CXL. The cornea with prior CXL treatment had less flattening effect due to the stiffening effect of prior CXL. [J Refract Surg. 2024;40(6):e392-e397.].

Does collagen cross linking have any effect on retinal circulation in patients with keratoconus? An optical coherence tomography angiography (OCTA) study.

BACKGROUND: We aimed to employ Optical Coherence Tomography Angiography (OCTA) to comprehensively assess changes in the optic nerve head (ONH) and macular perfusion before and after the Corneal Collagen Cross-Linking (CCL) procedure in patients with keratoconus. METHODS: A total of 22 keratoconus patient's candidate for CCL procedures were included based on specific criteria, with meticulous exclusion criteria in place to minimize potential confounders. Participants underwent OCTA assessments of the ONH and macula using the Spectralis OCT (Heidelberg) before CCL, as well as at 1- and 3-months post-CCL. MATLAB software was utilized for image analysis. RESULTS: The mean age of the participants was 20.09 ± 6.11, including 59% male, and the mean intraocular pressure (IOP) before the surgery was 13.59 ± 2.85 mmHg. Peripapillary Retinal nerve fiber layer (ppRNFL) thickness and overall retinal thickness remained stable post-CCL. However, significant alterations were observed in macular vessel density, emphasizing regional variations in vascular response. For macular large vessel density (LVD), both superficial and deep vascular complex (SVC and DVC) demonstrated significant differences between before surgery and the 3 months post-surgery follow-up (p < 0.001 and p = 0.002, respectively). Optic nerve head markers demonstrated relative stability, except for changes in avascular complex density, which was 49.2 ± 2.2% before the surgery and decrease to 47.6 ± 1.7% three months after the operation (P-value = 0.005). CONCLUSION: While CCL appears to maintain the integrity of certain ocular structures, alterations in macular perfusion post-CCL suggest potential effects on retinal blood supply. Long-term monitoring is crucial to understand the implications of these changes, particularly in the context of conditions such as diabetes.

A TME-enlightened protein-binding photodynamic nanoinhibitor for highly effective oncology treatment.

The efficiency of photodynamic therapy (PDT) is greatly dependent on intrinsic features of photosensitizers (PSs), but most PSs suffer from narrow diffusion distances and short life span of singlet oxygen (1O2). Here, to conquer this issue, we propose a strategy for in situ formation of complexes between PSs and proteins to deactivate proteins, leading to highly effective PDT. The tetrafluorophenyl bacteriochlorin (FBC), a strong near-infrared absorbing photosensitizer, can tightly bind to intracellular proteins to form stable complexes, which breaks through the space-time constraints of PSs and proteins. The generated singlet oxygen directly causes the protein dysfunction, leading to high efficiency of PSs. To enable efficient delivery of PSs, a charge-conversional and redox-responsive block copolymer POEGMA-b-(PAEMA/DMMA-co-BMA) (PB) was designed to construct a protein-binding photodynamic nanoinhibitor (FBC@PB), which not only prolongs blood circulation and enhances cellular uptake but also releases FBC on demand in tumor microenvironment (TME). Meanwhile, PDT-induced destruction of cancer cells could produce tumor-associated antigens which were capable to trigger robust antitumor immune responses, facilitating the eradication of residual cancer cells. A series of experiments in vitro and in vivo demonstrated that this multifunctional nanoinhibitor provides a promising strategy to extend photodynamic immunotherapy.

Photodynamic therapy using talaporfin sodium for non-totally resectable malignant glioma.

BACKGROUND: For malignant glioma, intraoperative photodynamic therapy (PDT) using talaporfin sodium is a powerful tool for local tumor control, when gross total removal is performed. However, the efficacy of PDT for non-totally resectable malignant glioma has not been clearly confirmed. Therefore, the purpose of this study was to clarify the usefulness of PDT using talaporfin sodium for non-totally resectable malignant glioma. METHODS: Eighteen patients with malignant glioma (16 new onset, 2 recurrent) in whom gross total removal was judged to be difficult from the images obtained before surgery were evaluated. Fifteen patients had glioblastoma (14 newly diagnosed, 1 recurrent), and 3 patients had anaplastic oligodendroglioma (2 newly diagnosed, 1 recurrent). The whole resection cavity was subjected to PDT during the surgery. For newly diagnosed glioblastoma, postoperative therapy involved the combined use of radiation and temozolomide. Bevacizumab treatment was also started at an early stage after surgery. RESULTS: In some patients, reduction of the residual tumor was observed at an early stage of chemoradiotherapy after the surgery, suggesting the positive effect of PDT. Recurrence occurred in 15 of the 18 patients during the course of treatment. Distant recurrence occurred in 8 of these 15 patients, despite good local tumor control. In the 14 patients with newly diagnosed glioblastoma, the median progression-free survival was almost 10.5 months, and the median overall survival was almost 16.9 months. CONCLUSIONS: PDT for malignant glioma is expected to slightly improve local tumor control for non-totally resectable lesions.

Clinical versus Histological Assessment of Basal Cell Carcinoma Subtype and Thickness of Tumours Selected for Photodynamic Therapy.

Photodynamic therapy is an approved treatment for primary, superficial, and small nodular basal cell carcinomas with a thickness of < 2 mm located on low-risk sites. Histologically verified basal cell carcinomas clinically assessed as suited for photodynamic therapy were included. The study aimed to investigate the agreement between clinical and histological assessments of basal cell carcinoma subtypes and thickness of tumours selected for photodynamic therapy with histopathological evaluation as a reference. A total of 343 tumours were included. The agreement between clinical and histological diagnosis of basal cell carcinoma subtype was 72% (p < 0.001). Clinical assessment of subtype had a sensitivity of 93% and specificity of 55% for superficial tumours and a sensitivity of 55% and specificity of 85% for nodular tumours. The mean ± SD thickness values by clinical and histological assessments were 0.95 ± 0.53 and 0.86 ± 0.75. The difference of 0.09 mm was statistically significant (p = 0.017), but not considered to be clinically relevant, although the differences between specific subgroups could be relevant. Among basal cell carcinomas clinically diagnosed as superficial, 91% were histologically consistent with the current photodynamic therapy criteria. The main results suggest that histopathological evaluation should precede photodynamic therapy to ensure selection of suitable basal cell carcinomas. In selected cases, the clinical diagnosis alone may be adequate before proceeding with photodynamic therapy.

Plants-occurring Anthraquinones as Photosensitive Compounds for Photodynamic Method: A Critical Overview.

The review focuses on the recent knowledge on natural anthraquinones (AQs) of plant origin and their potential for application in an exclusive medicinal curative and palliative method named photodynamic therapy (PDT). Green approach to PDT is associated with photosensitizers (PS) from plants or other natural sources and excitation light in visible spectrum. The investigations of plants are of high research interests due to their unique health supportive properties as herbs and the high percentage availability to obtain compounds with medical value. Up-to-date many naturally occurring compounds with therapeutic properties are known and are still under investigations. Some natural quinones have already been evaluated and clinically approved as anti-tumor agents. Recent scientific interests are beyond their common medical applications but also in directions to their photo-properties as natural PSs. The study presents a systematic searches on the latest knowledge on AQ derivatives that are isolated from the higher plants as photosensitizers for PDT applications. The natural quinones have been recognized with functions of natural dyes since the ancient times. Lately, AQs have been explored due to their biological activity including the photosensitive properties useful for PDT especially towards medical problems with no other alternatives. The existing literature' overview suggests that natural AQs possess characteristics of valuable PSs for PDT. This method is based on an application of a photoactive compound and light arrangement in oxygen media, such that the harmful general cytotoxicity could be avoided. Moreover, the common anticancer and antimicrobial drug resistance has been evaluated with very low occurrence after PDT. Natural AQs have been focused the scientific efforts to further developments because of the high range of natural sources, desirable biocompatibility, low toxicity, minimal side effects and low accident of drug resistance, together with their good photosensitivity and therapeutic capacity. Among the known AQs, only hypericin has been studied in anticancer clinical PDT. Currently, the natural PSs are under intensive research for the future PDT applications for diseases without alternative effective treatments.

Update on corneal crosslinking for keratoconus and corneal ectasia.

PURPOSE OF REVIEW: To review corneal crosslinking for keratoconus and corneal ectasia, and recent developments in the field. This study will review the mechanism of crosslinking, clinical approaches, current results, and potential future innovations. RECENT FINDINGS: Corneal crosslinking for keratoconus was first approved by U.S. FDA in 2016. Recent studies have confirmed the general long-term efficacy of the procedure in decreasing progression of keratoconus and corneal ectasia. New types of crosslinking protocols, such as transepithelial treatments, are under investigation. In addition, adjunctive procedures have been developed to improve corneal contour and visual function in these patients. SUMMARY: Crosslinking has been found to be well tolerated and effective with the goal of decreasing progression of ectatic corneal diseases, keratoconus and corneal ectasia after refractive surgery. Studies have shown its long-term efficacy. New techniques of crosslinking and adjunctive procedures may further improve treatments and results.

Long-term outcomes of corneal crosslinking.

PURPOSE OF REVIEW: This manuscript summarizes contemporary research from 2018 to 2023 evaluating long-term (≥2 years) outcomes of corneal crosslinking (CXL) for progressive keratoconus (KCN). RECENT FINDINGS: The standard Dresden protocol (SDP) has been utilized clinically since the early 2000 s to treat ectatic disorders, primarily progressive KCN and postrefractive ectasia. Various modifications have since been introduced including accelerated and transepithelial protocols, which are aimed at improving outcomes or reducing complications. This review summarizes data demonstrating that the SDP halts disease progression and improves various visual and topographic indices (UDVA, CDVA, Kmax, K1, K2) up to 13 years postoperatively. Accelerated and transepithelial protocols have been found to be well tolerated alternatives to SDP with similar efficacy profiles. Studies focusing on pediatric populations identified overall higher progression rates after CXL. All protocols reviewed had excellent safety outcomes in adults and children. SUMMARY: Recent studies revealed that SDP successfully stabilizes KCN long term, and a variety of newer protocols are also effective. Pediatric patients may exhibit higher progression rates after CXL. Further research is required to enhance the efficacy and ease of these protocols.

Severe hypotension and postoperative cardiac arrest caused by 5-aminolevulinic acid: a case report.

BACKGROUND: Although 5-aminolevulinic acid is useful for the photodynamic diagnosis of bladder tumors, it often causes severe intraoperative hypotension. We report a case of postoperative cardiac arrest in addition to severe intraoperative hypotension, probably owing to the use of 5-aminolevulinic acid. CASE PRESENTATION: An 81-year-old Japanese man was scheduled to undergo transurethral resection of bladder tumor. The patient took 5-aminolevulinic acid orally 2 hours before entering the operating room. After the induction of anesthesia, his blood pressure decreased to 47/33 mmHg. The patient's hypotension did not improve even after noradrenaline was administered. After awakening from anesthesia, the patient's systolic blood pressure increased to approximately 100 mmHg, but approximately 5 hours after returning to the ward, cardiac arrest occurred for approximately 12 seconds. CONCLUSION: We experienced a case of postoperative cardiac arrest in a patient, probably owing to the use of 5-aminolevulinic acid. Although the cause of cardiac arrest is unknown, perioperative hemodynamic management must be carefully performed in patients taking 5-aminolevulinic acid.

Nanomaterials-based advanced systems for photothermal / photodynamic therapy of oral cancer.

The traditional clinical approaches for oral cancer consist of surgery, chemotherapy, radiotherapy, immunotherapy, and so on. However, these treatments often induce side effects and exhibit limited efficacy. Photothermal therapy (PTT) emerges as a promising adjuvant treatment, utilizing photothermal agents (PTAs) to convert light energy into heat for tumor ablation. Another innovative approach, photodynamic therapy (PDT), leverages photosensitizers (PSs) and specific wavelength laser irradiation to generate reactive oxygen species (ROS), offering an effective and non-toxic alternative. The relevant combination therapies have been reported in the field of oral cancer. Simultaneously, the advancement of nanomaterials has propelled the clinical application of PTT and PDT. Therefore, a comprehensive understanding of PTT and PDT is required for better application in oral cancer treatment. Here, we review the use of PTT and PDT in oral cancer, including noble metal materials (e.g., Au nanoparticles), carbon materials (e.g., graphene oxide), organic dye molecules (e.g., indocyanine green), organic molecule-based agents (e.g., porphyrin-analog phthalocyanine) and other inorganic materials (e.g., MXenes), exemplify the advantages and disadvantages of common PTAs and PSs, and summarize the combination therapies of PTT with PDT, PTT/PDT with chemotherapy, PTT with radiotherapy, PTT/PDT with immunotherapy, and PTT/PDT with gene therapy in the treatment of oral cancer. The challenges related to the PTT/PDT combination therapy and potential solutions are also discussed.

Association of 5-aminolevulinic acid fluorescence guided resection with photodynamic therapy in recurrent glioblastoma: a matched cohort study.

PURPOSE: Glioblastoma is a malignant and aggressive brain tumour that, although there have been improvements in the first line treatment, there is still no consensus regarding the best standard of care (SOC) upon its inevitable recurrence. There are novel adjuvant therapies that aim to improve local disease control. Nowadays, the association of intraoperative photodynamic therapy (PDT) immediately after a 5-aminolevulinic acid (5-ALA) fluorescence-guided resection (FGR) in malignant gliomas surgery has emerged as a potential and feasible strategy to increase the extent of safe resection and destroy residual tumour in the surgical cavity borders, respectively. OBJECTIVES: To assess the survival rates and safety of the association of intraoperative PDT with 5-ALA FGR, in comparison with a 5-ALA FGR alone, in patients with recurrent glioblastoma. METHODS: This article describes a matched-pair cohort study with two groups of patients submitted to 5-ALA FGR for recurrent glioblastoma. Group 1 was a prospective series of 11 consecutive cases submitted to 5-ALA FGR plus intraoperative PDT; group 2 was a historical series of 11 consecutive cases submitted to 5-ALA FGR alone. Age, sex, Karnofsky performance scale (KPS), 5-ALA post-resection status, T1-contrast-enhanced extent of resection (EOR), previous and post pathology, IDH (Isocitrate dehydrogenase), Ki67, previous and post treatment, brain magnetic resonance imaging (MRI) controls and surgical complications were documented. RESULTS: The Mantel-Cox test showed a significant difference between the survival rates (p = 0.008) of both groups. 4 postoperative complications occurred (36.6%) in each group. As of the last follow-up (January 2024), 7/11 patients in group 1, and 0/11 patients in group 2 were still alive. 6- and 12-months post-treatment, a survival proportion of 71,59% and 57,27% is expected in group 1, versus 45,45% and 9,09% in group 2, respectively. 6 months post-treatment, a progression free survival (PFS) of 61,36% and 18,18% is expected in group 1 and group 2, respectively. CONCLUSION: The association of PDT immediately after 5-ALA FGR for recurrent malignant glioma seems to be associated with better survival without additional or severe morbidity. Despite the need for larger, randomized series, the proposed treatment is a feasible and safe addition to the reoperation.

Photoimmunotherapy of Prostate Cancer With Antibody and Fab Fragments Targeting the Prostate Specific Membrane Antigen.

BACKGROUND/AIM: The standard treatment for localized prostate cancer involves surgical removal of the prostate with curative intent. However, when tumor cells persist in the operation site, there is high risk of local recurrence and tumor spread, leading to stressful follow-up treatments, impaired quality of life, and reduced overall survival. This study examined photoimmunotherapy (PIT) as a new treatment option for prostate cancer cells. MATERIALS AND METHODS: We generated conjugates consisting of either a humanized antibody or Fab fragments thereof targeting the prostate specific membrane antigen (PSMA), along with our silicon phthalocyanine photosensitizer dye WB692-CB1. PSMA-expressing prostate cancer cells were incubated with the antibody dye or Fab dye conjugates and cell binding was measured using flow cytometry. Cells were irradiated with varying doses of red light for dye activation, and cytotoxicity was determined by erythrosin B staining and subsequent analysis using a Neubauer counting chamber. RESULTS: Specific cytotoxicity was induced with the antibody dye conjugate in the prostate cancer cells in a light dose-dependent manner. Treatment of the cells with the Fab dye conjugate resulted in lower cytotoxicity, which could be attributed to a reduced binding affinity and a reduced dye uptake of the Fab fragment. CONCLUSION: Our new antibody dye and Fab dye conjugates offer potential for future intraoperative PIT in patients with localized prostate cancer, with the aim to ensure complete removal of tumor cells from the surgical area, to avoid local recurrence, and to improve clinical outcome.

Chemo-photodynamic antitumour therapy based on Er-doped upconversion nanoparticles coated with hypocrellin B and MnO2.

An antitumour chemo-photodynamic therapy nanoplatform was constructed based on phospholipid-coated NaYF4: Yb/Er upconversion nanoparticles (UCNPs). In this work, the amphiphilic block copolymer DSPE-PEG2000 was combined with the surface ligand oleic acid of the UCNPs through hydrophobic interaction to form liposomes with a dense hydrophobic layer in which the photosensitizer hypocrellin B (HB) was assembled. The coated HB formed J-aggregates, which caused a large redshift in the absorption spectrum and improved the quantum efficiency of energy transfer. Furthermore, MnO2 nanosheets grew in-situ on the liposomes through OMn coordination. Therefore, a multifunctional tumour microenvironment (TME)-responsive theranostic nanoplatform integrating photodynamic therapy (PDT) and chemodynamic therapy (CDT) was successfully developed. The results showed that this NIR-mediated chemo-photodynamic therapy nanoplatform was highly efficient for oncotherapy.

Energy-storing DNA-based hydrogel remodels tumor microenvironments for laser-free photodynamic immunotherapy.

Photodynamic therapy (PDT) is a promising modality for cancer treatment. However, limited tissue penetration of external radiation and complicated tumor microenvironments (TMEs) restrict the antitumor efficiency of PDT. Herein, we report an energy-storing DNA-based hydrogel, which enables tumor-selective PDT without external radiation and regulates TMEs to achieve boosted PDT-mediated tumor immunotherapy. The system is constructed with two ultralong single-stranded DNA chains, which programmed partial complementary sequences and repeated G-quadruplex forming AS1411 aptamer for photosensitizer loading via hydrophobic interactions and π-π stacking. Then, energy-storing persistent luminescent nanoparticles are incorporated to sensitize PDT selectively at tumor site without external irradiation, generating tumor antigen to agitate antitumor immune response. The system catalytically generates O2 to alleviate hypoxia and releases inhibitors to reverse the IDO-related immunosuppression, synergistically remodeling the TMEs. In the mouse model of breast cancer, this hydrogel shows a remarkable tumor suppression rate of 78.3 %. Our study represents a new paradigm of photodynamic immunotherapy against cancer by combining laser-free fashion and TMEs remodeling.

Facile one-pot synthesis of Ir(III) Bodipy polymeric gemini nanoparticles for tumor selective NIR photoactivated anticancer therapy.

Over the last decades, a variety of metal complexes have been developed as chemotherapeutic agents. Despite the promising therapeutic prospects, the vast majority of these compounds suffer from low solubility, poor pharmacological properties, and most importantly poor tumor accumulation. To circumvent these limitations, herein, the incorporation of cytotoxic Ir(III) complexes and a variety of photosensitizers into polymeric gemini nanoparticles that selectively accumulate in the tumorous tissue and could be activated by near-infrared (NIR) light to exert an anticancer effect is reported. Upon exposure to light, the photosensitizer is able to generate singlet oxygen, triggering the rapid dissociation of the nanostructure and the activation of the Ir prodrug, thereby initiating a cascade of mitochondrial targeting and damage that ultimately leads to cell apoptosis. While selectively accumulating into tumorous tissue, the nanoparticles achieve almost complete eradication of the cisplatin-resistant cervical carcinoma tumor in vivo upon exposure to NIR irradiation.

A perylene diimide probe for NIR-II fluorescence imaging guided photothermal and type I/type II photodynamic synergistic therapy.

Phototherapy has garnered significant attention in the past decade. Photothermal and photodynamic synergistic therapy combined with NIR fluorescence imaging has been one of the most attractive treatment options because of the deep tissue penetration, high selectivity and excellent therapeutic effect. Benefiting from the superb photometrics and ease of modification, perylene diimide (PDI) and its derivatives have been employed as sensing probes and therapeutic agents in the biological and biomedical research fields, and exhibiting excellent potential. Herein, we reported the development of a novel organic small-molecule phototherapeutic agent, PDI-TN. The absorption of PDI-TN extends into the NIR region, which provides feasibility for NIR phototherapy. PDI-TN overcomes the traditional Aggregation-Caused Quenching (ACQ) effect and exhibits typical characteristics of Aggregation-Induced Emission (AIE). Subsequently, PDI-TN NPs were obtained by using an amphiphilic triblock copolymer F127 to encapsulate PDI-TN. Interestingly, the PDI-TN NPs not only exhibit satisfactory photothermal effects, but also can generate O2•- and 1O2 through type I and type II pathways, respectively. Additionally, the PDI-TN NPs emit strong fluorescence in the NIR-II region, and show outstanding therapeutic potential for in vivo NIR-II fluorescence imaging. To our knowledge, PDI-TN is the first PDI derivative used for NIR-II fluorescence imaging-guided photodynamic and photothermal synergistic therapy, which suggests excellent potential for future biological/biomedical applications.

Photosensitive AIEgens sensitize bacteria to oxidative damage and modulate the inflammatory responses of macrophages to salvage the photodynamic therapy against MRSA.

The urgent need for antimicrobial agents to combat infections caused by multidrug-resistant bacteria facilitates the exploration of alternative strategies such as photosensitizer (PS)-mediated photoinactivation. However, increasing studies have discovered uncorrelated bactericidal activities among PSs possessing similar photodynamic and pathogen-targeted properties. To optimize the photodynamic therapy (PDT) against infections, we investigated three type-I PSs of D-π-A AIEgens TI, TBI, and TTI. The capacities of reactive oxygen species (ROS) generation of TI, TBI, and TTI did not align with their bactericidal activities. Despite exhibiting the lowest photodynamic efficiency, TI exhibited the highest activities against methicillin-resistant Staphylococcus aureus (MRSA) by impairing the anti-oxidative responses of bacteria. By comparison, TTI, characterized by the strongest ROS production, inactivated intracellular MRSA by potentiating the inflammatory response of macrophages. Unlike TI and TTI, TBI, despite possessing moderate photodynamic activities and inducing ROS accumulation in both MRSA and macrophages, did not exhibit any antibacterial activity. Therefore, relying on the disturbed anti-oxidative metabolism of pathogens or potentiated host immune responses, transient ROS bursts can effectively control bacterial infections. Our study reevaluates the contribution of photodynamic activities of PSs to bacterial elimination and provides new insights into discovering novel antibacterial targets and agents.

Root Canal Disinfection in Permanent Molars with Apical Lesion by Antimicrobial Photodynamic Therapy: Protocol for a Blind Randomized Clinical Trial.

Objective: The proposed study aims to compare the effectiveness of conventional endodontic treatment (ET) with that of ET associated with antimicrobial photodynamic therapy (aPDT) in patients with apical lesion. Methods: Controlled, double-blind, randomized clinical trial (RCT); superiority study with three parallel arms. Randomization will be conducted in exchange blocks of six, with allocation 1:1:1. The control group will receive conventional ET, while experimental group 1 (EG1) will receive conventional ET + aPDT with laser at 660 nm, fluence of 600 J/cm2; EG2 will receive conventional ET + aPDT with laser at 660 nm, fluence of 1200 J/cm2. The primary outcome will be canal disinfection before treatment, measured by analysis of colony formation (CFU/mL) and the success rate measured after 6 months on the clinical and radiographic evaluations. The mean and standard deviation will be calculated for continuous outcomes, and the CFU/mL mean between groups will be evaluated by ANOVA test. The Chi-squared test will be calculated for binary outcomes. A logistic regression analysis will be performed to assess differences in the success rate between groups, adjusted for the covariates. The Stata 18 software will be used, with a significance threshold of 5%. Conclusions: Few RCTs have evaluated the effectiveness of aPDT in root canal disinfection in patients with permanent dentition presenting apical lesion. New RCTs with larger numbers of participants are needed to support using aPDT as an adjuvant to conventional ET in root canal disinfection for routine use in clinical practice. The trial was registered prospectively in ClinicalTrials.gov (NCT05916859).

Diagnostic utility of in vivo confocal microscopy in Acanthamoeba keratitis following corneal crosslinking.

Acanthamoeba keratitis (AK) is a rare but potentially sight-threatening complication of corneal collagen crosslinking (CXL) for keratoconus. In this report, we describe an early adolescent male who underwent routine CXL for progressive keratoconus in his left eye. Preprocedural left visual acuity (VA) was 6/9. At day 5 postprocedure, multifocal corneal infiltrates were identified. Corneal scrape, bandage contact lens cultures and herpetic and Acanthamoeba PCR were negative. In vivo, confocal microscopy (IVCM) identified Acanthamoeba cysts within the corneal stroma. Intensive amoebicidal therapy was initiated, but recovery was complicated by significant inflammation, resulting in widespread aggressive corneal vascularisation necessitating topical steroids and steroid-sparing agents. At 10 months, his left VA was 6/24. This report emphasises the importance of maintaining a high index of suspicion for AK in cases of post-CXL microbial keratitis and highlights the diagnostic value of IVCM, particularly in culture-negative and PCR-negative cases.