The Microbiome Matters: Its Impact on Cancer Development and Therapeutic Responses.

In the evolving landscape of cancer research, the human microbiome emerges as a pivotal determinant reshaping our understanding of tumorigenesis and therapeutic responses. Advanced sequencing technologies have uncovered a vibrant microbial community not confined to the gut but thriving within tumor tissues. Comprising bacteria, viruses, and fungi, this diverse microbiota displays distinct signatures across various cancers, with most research primarily focusing on bacteria. The correlations between specific microbial taxa within different cancer types underscore their pivotal roles in driving tumorigenesis and influencing therapeutic responses, particularly in chemotherapy and immunotherapy. This review amalgamates recent discoveries, emphasizing the translocation of the oral microbiome to the gut as a potential marker for microbiome dysbiosis across diverse cancer types and delves into potential mechanisms contributing to cancer promotion. Furthermore, it highlights the adverse effects of the microbiome on cancer development while exploring its potential in fortifying strategies for cancer prevention and treatment.

Autolysis of Pseudomonas aeruginosa Quorum-Sensing Mutant Is Suppressed by Staphylococcus aureus through Iron-Dependent Metabolism.

Microorganisms usually coexist as a multifaceted polymicrobial community in the natural habitats and at mucosal sites of the human body. Two opportunistic human pathogens, Pseudomonas aeruginosa and Staphylococcus aureus commonly coexist in the bacterial infections for hospitalized and/or immunocompromised patients. Here, we observed that autolysis of the P. aeruginosa quorum-sensing (QS) mutant (lasRmvfR) was suppressed by the presence of the S. aureus cells in vitro. The QS mutant still displayed killing against S. aureus cells, suggesting the link between the S. aureus-killing activity and the autolysis suppression. Independent screens of the P. aeruginosa transposon mutants defective in the S. aureus-killing and the S. aureus transposon mutants devoid of the autolysis suppression revealed the genetic link between both phenotypes, suggesting that the iron-dependent metabolism involving S. aureus exoproteins might be central to both phenotypes. The autolysis was suppressed by iron treatment as well. These results suggest that the interaction between P. aeruginosa and S. aureus might be governed by mechanisms that necessitate the QS circuitry as well as the metabolism involving the extracellular iron resources during the polymicrobial infections in the human airway.

Dysthyroid optic neuropathy: a case series at a tertiary ophthalmic referral centre.

BACKGROUND/OBJECTIVES: To determine risk factors and treatment outcomes in dysthyroid optic neuropathy (DON) at a single tertiary ophthalmic centre. METHODS: Retrospective audit of DON patients who have received intravenous methylprednisolone (IVMP) therapy at Royal Victorian Eye and Ear Hospital, Melbourne, Australia from July 2015 to October 2021. RESULTS: Study included 24 patients (58% female) with an average age of 59.8 ± 14.7 years at DON diagnosis. Majority (92%) had Graves' hyperthyroidism and 77% had a smoking history. At diagnosis, average visual acuity (VA) of worse eye was LogMAR 0.46, and 48% had relative afferent pupillary defect. Proptosis (89%) and diplopia (73%) were most commonly present at diagnosis. 78% showed predominantly extra-ocular muscle enlargement, and apical crowding (52%) on radiology. 38% (n = 9/24) responded to IVMP alone, 58% (n = 14/24) progressed to surgical orbital decompression. The average total cumulative dose of IVMP during DON treatment was 6.8 ± 1.9 g. 29% required further treatment after IVMP and surgical decompression, 4 (17%) had additional radiotherapy, and three (13%) required immuno-modulatory therapy. Average final VA was LogMAR 0.207, with all patients having inactive TED at final follow-up (mean 1.7 years). In refractory DON cases, 71% retained VA ≥ 6/9 and 48% had DON reversal. CONCLUSIONS: DON patients typically present in late 50s, with a smoking history and predominant extra-ocular muscle enlargement. High-dose IVMP fully resolved DON in only 38%. A considerable proportion required urgent orbital decompression. Most patients retained good vision at final follow-up.

An iron-chelating sulfonamide identified from Drosophila-based screening for antipathogenic discovery.

We exploited bacterial infection assays using the fruit fly Drosophila melanogaster to identify anti-infective compounds that abrogate the pathological consequences in the infected hosts. Here, we demonstrated that a pyridine-3-N-sulfonylpiperidine derivative (4a) protects Drosophila from the acute infections caused by bacterial pathogens including Pseudomonas aeruginosa. 4a did not inhibit the growth of P. aeruginosa in vitro, but inhibited the production of secreted toxins such as pyocyanin and hydrogen cyanide, while enhancing the production of pyoverdine and pyochelin, indicative of iron deprivation. Based on its catechol moiety, 4a displayed iron-chelating activity in vitro toward both iron (II) and iron (III), more efficiently than the approved iron-chelating drugs such as deferoxamine and deferiprone, concomitant with more potent antibacterial efficacy in Drosophila infections and unique transcriptome profile. Taken together, these results delineate a Drosophila-based strategy to screen for antipathogenic compounds, which interfere with iron uptake crucial for bacterial virulence and survival in host tissues.

Biopsy for molecular risk stratification in uveal melanoma: Yields and molecular characteristics in 119 patients.

BACKGROUND: Prognostic cytological and molecular features of uveal melanoma have been well researched and are essential in management. Samples can be obtained in vivo through fine needle aspirate biopsy, vitrector cutter, forceps or post-enucleation for off-site testing. This study aims to examine cytological and chromosome microarray yields of these samples. METHODS: A retrospective cohort analysis of 119 uveal melanoma biopsies submitted to our laboratory. Samples included those taken in vivo (n = 57) and post-enucleation (n = 62). Patient and tumour features were collected including age, sex, primary tumour location, basal diameter and tumour height. Prognostic outcomes measured include cell morphology, chromosomal status and immunohistochemistry. RESULTS: Post-enucleation biopsies accounted for just over half of our samples (52%). Post-enucleation samples had a more successful genetic yield than in vivo biopsies (77% vs. 50%, p = 0.04) though there was no difference for cytological yields. There was no difference in cytological or microarray yields between instruments. The vitrector biopsy group had the smallest tumour thickness (5 mm vs. 10 mm [fine-needle aspirate biopsy], p = 0.003). There was a strong correlation between monosomy 3, BAP1 aberrancy and epithelioid cell type in post-enucleation samples (Tb  = 0.742, p = 0.005). However, epithelioid morphology was not associated with either monosomy 3 (p = 0.07) or BAP1 aberrancy (p = 0.24) for in vivo biopsies. CONCLUSIONS: All three biopsy instruments provide similar cytological yields as post-enucleation sampling, although post-enucleation samples had a more successful chromosome microarray yield. Epithelioid cytomorphology alone is insufficient for prognostication in in vivo biopsies, immunohistochemistry would be a useful surrogate test.

A phage protein-derived antipathogenic peptide that targets type IV pilus assembly.

Phage-inspired antibacterial discovery is a new approach that recruits phages in search for antibacterials with new molecular targets, in that phages are the biological entities well adapted to hijack host bacterial physiology in favor of their own thrive. We previously observed that phage-mediated twitching motility inhibition was effective to control the acute infections caused by Pseudomonas aeruginosa and that the motility inhibition was attributed to the delocalization of PilB, the type IV pilus (TFP) assembly ATPase by binding of the 136-amino acid (aa) phage protein, Tip. Here, we created a series of truncated and point-mutant Tip proteins to identify the critical residues in the Tip bioactivity: N-terminal 80-aa residues were dispensable for the Tip activity; we identified that Asp82, Leu84, and Arg85 are crucial in the Tip function. Furthermore, a synthetic 15-aa peptide (P1) that corresponds to Leu73 to Ala87 is shown to suffice for PilB delocalization, twitching inhibition, and virulence attenuation upon exogenous administration. The transgenic flies expressing the 15-aa peptide were resistant to P. aeruginosa infections as well. Taken together, this proof-of-concept study reveals a new antipathogenic peptide hit targeting bacterial motility and provides an insight into antibacterial discovery targeting TFP assembly.

Evaluation of the efficacy of cysteamine cream compared to hydroquinone in the treatment of melasma: A randomised, double-blinded trial.

BACKGROUND/OBJECTIVE: Melasma is a commonly acquired disorder of hyperpigmentation that often poses a therapeutic challenge for dermatologists. Recently, cysteamine cream has shown promising results compared to placebo. This study aims to determine the efficacy of cysteamine cream compared to hydroquinone cream in the treatment of melasma. METHODS: A randomised, double-blinded, single-centre trial was conducted in Victoria, Australia. 20 recruited participants were given either cysteamine cream or hydroquinone cream for 16 weeks. The primary outcome measure was a change in the modified Melasma Area and Severity Index (mMASI). Quality of life at baseline and week 16 as well as standard digital photography at each follow-up visit was assessed as secondary outcome measures. RESULTS: At week 16, 14 participants completed the study with 5 participants in the cysteamine group and 9 patients in the hydroquinone group. In the intention to treat analysis, there was a 1.52 ± 0.69 (21.3%) reduction in mMASI for the cysteamine group and a 2.96 ± 1.15 (32%) reduction in the hydroquinone group. The difference between groups was not statistically significant (P = 0.3). Hydroquinone cream was generally better tolerated that cysteamine cream. CONCLUSION: Our study suggests that topical cysteamine may have comparable efficacy to topical hydroquinone. Cysteamine thus provides a possible alternative to patients and clinicians who wish to avoid or rotate off topical hydroquinone. While side effects were more common for participants using cysteamine compared with hydroquinone, these were mild and reversible. Larger studies comparing cysteamine and hydroquinone are required to support these findings.

Eyelid basal cell carcinoma with neuroendocrine differentiation: a case report and literature review.

Basal cell carcinoma (BCC) is the most common type of malignant tumor in the periocular region. BCCs with neuroendocrine differentiation in the periocular region, however, have not been described in the literature.We present a retrospective case review of a patient with an eyelid BCC with neuroendocrine differentiation. Demographical, clinical, radiological, surgical, histological, and follow-up data are presented.The patient presented with a slow-growing lesion of the eyelid with associated epiphora and dull ache. Initial incisional biopsy of the lesion revealed an infiltrating carcinoma composed of epithelial cells. Immunohistochemistry showed that the tumor was positive for p40, Ber-Ep4, neuron specific enolase (NSE), chromogranin A, CD56 (NCAM), and synaptophysin. The pathology from the margin-controlled excision showed basosquamous cell carcinoma with neuroendocrine differentiation. Tumor recurrence was not detected clinically at the post-operative six-month review.BCC with neuroendocrine marker positivity represents an important diagnostic differential for rare eyelid carcinomas such as primary cutaneous neuroendocrine carcinoma and metastatic small cell carcinoma that have a poor prognosis. The prognostic importance of neuroendocrine marker positivity in BCCs is uncertain. The present case provides further evidence for neuroendocrine differentiation in BCCs.

The Usefulness of Anti-acetylcholine Receptor Binding Antibody Testing in Diagnosing Ocular Myasthenia Gravis.

BACKGROUND: Anti-acetylcholine receptor antibody (AChR-Abs) testing is a safe and simple ancillary method for confirming the diagnosis of myasthenia gravis. Despite the test's high sensitivity (85%-90%) for generalized myasthenia gravis, AChR-Abs testing has been reported to have a low sensitivity 44%-66% for ocular myasthenia gravis (OMG). The aim of the study is to assess the effectiveness of AChR binding Abs testing for diagnosing OMG by evaluating the test's sensitivity, specificity, positive predictive value, and negative predictive value. METHODS: A retrospective chart review on 114 OMG suspects who presented to the emergency department of a tertiary eye center in Victoria, Australia, was completed. The patients presented with diplopia alone, ptosis alone, or the combination of diplopia and ptosis. All participants were followed up longitudinally in the neuro-ophthalmology outpatient clinics for the average of 2.8 months, where they have received AChR binding testing. The final diagnosis was only given to the patients who either were seropositive for AChR binding Abs and had a high clinical suspicion of OMG, or the patient who was seronegative for AChR binding Abs but was regarded as likely to have OMG clinically and responded to the diagnostic treatments (pyridostigmine bromide and immunosuppressant therapy). RESULTS: The sensitivity of AChR binding Abs testing in diagnosing OMG was higher (80%; 95% confidence interval [CI], 51.91%-95.67%) than previously reported (44%-66%). AChR binding Abs testing also had a high specificity (98.99%; 95% CI, 94.50%-99.97%) and positive predictive value (92.31%; 95% CI, 62.68%-98.85%). CONCLUSION: The study suggests the higher utility of the AChR binding Abs testing in diagnosing OMG due to its high sensitivity, specificity, and positive predictive value.

Two-year outcomes of the treat-and-extend regimen using aflibercept for treating diabetic macular oedema.

This study was performed to investigate the efficacy of the treat-and-extend regimen using aflibercept for treating diabetic macular oedema (DME). This prospective, multicentre, interventional, single-arm, 104-week clinical trial included 48 patients with DME visual impairment. The patients' eyes received five consecutive intravitreal injections (2 mg aflibercept) every four weeks with two-week adjustments based on central subfield macular thickness (CSMT) changes. Injections were deferred when CSMT was stable. The number of injections, best-corrected visual acuity (BCVA), CSMT, and diabetic retinopathy severity scale scores were analysed. Compared to baseline, BCVA improved by + 9.1 letters at 52 weeks and was maintained with + 9.4-letter gain at 104 weeks (P < 0.001). Between baseline and 104 weeks, CSMT decreased from 489 to 298 µm (P < 0.001) and eyes with vision ≥ 20/40 increased from 17.4 to 43.5% (P = 0.007). The mean number of injections decreased from 8.5 in year one to 3.9 in year two. The injection interval was extended to ≥ 12 weeks in 56.5% of patients. The treat-and-extend regimen of aflibercept in DME showed 2-year efficacy comparable to that of fixed dosing regimens. The flexible dosing of this regimen reduced the number of injections in year two while maintaining efficacy.

Repositioning of a mucolytic drug to a selective antibacterial against Vibrio cholerae.

Drug repositioning, the approach to explore existing drugs for use in new therapeutic indications, has emerged as an alternative drug development strategy. In this study, we found that a mucolytic drug, N-acetylcysteine (NAC) showed antibacterial activity against Vibrio cholerae. NAC can provide acid stress that selectively inhibited the growth of V. cholerae among other bacterial pathogens. To address the antibacterial mechanism of NAC against V. cholerae, six acr (acetylcys-teine-resistant) mutants were isolated from 3,118 random transposon insertion clones. The transposon insertion sites of the six mutants were mapped at the five genes. All these mutants did not display NAC resistance under acidic conditions, despite their resistance to NAC under alkaline conditions, indicating that the NAC resistance directed by the acr mutations was independent of the unusual pH-sensitivity of V. cholerae. Furthermore, all these mutants displayed attenuated virulence and reduced biofilm formation, suggesting that the acr genes are required for pathogenesis of V. cholerae. This study validates the relevance of drug repositioning for antibacterials with new modes of action and will provide an insight into a novel antibacterial therapy for V. cholerae infections to minimize side effects and resistance emergence.

One-Year Results of Treatment of Diabetic Macular Edema with Aflibercept Using the Treat-and-Extend Dosing Regimen: the VIBIM Study.

INTRODUCTION: The purpose of this study was to report the one-year results of treatment of diabetic macular edema (DME) with aflibercept using a treat-and-extend regimen (TER). METHODS: This was a prospective, multicenter, single-arm study planned for 2 years. The eyes received 5 consecutive intravitreal injections of 2 mg of aflibercept every 4 weeks, and the interval between injections was then adjusted by 2 weeks based on changes in the central subfield macular thickness (CSMT). If the CSMT was worse, stable, or better, the interval was shortened, extended, or maintained, respectively. The primary outcome measure was the change in best-corrected visual acuity (BCVA) from baseline to 104 weeks, and the secondary outcome was the change in BCVA from baseline to 52 weeks. RESULTS: Of the 48 patients enrolled, 46 completed a 1-year visit. BCVA improved significantly by 9.1 letters (95% confidence interval: 5.3-13.0 letters) from 56.2 letters at baseline (p < 0.001), and CSMT decreased by -171.7 µm from 489.4 to 317.7 µm (p < 0.001). The proportion of eyes having 20/40 or better vision increased from 17.4 to 41.3%, and the proportion of eyes that gained ≥15 letters was 28.3%. The mean number of injections was 8.5 times for 52 weeks. Worsening of macular edema did not occur in 76.1% of eyes during the extension period, and the interval between injections was extended to 12 weeks in 73.9% of eyes at 52 weeks. CONCLUSIONS: The TER showed 1-year efficacy comparable to that of the fixed dosing regimen of pivotal trials, and its flexible dosing would prevent overtreatment.

A case report of infectious scleritis with corneal ulcer caused by Scedosporium aurantiacum.

RATIONALE: Scedosporium species is rare pathogen of ocular infection. The accurate diagnosis is delaying in many cases and the clinical prognosis is poor due to its resistance to antifungal agents. This report describes a patient with infectious scleritis and corneal ulcer caused by Scedosporium auranticum infection who required enucleation to control the infection. PATIENT CONCERNS: A 70-year-old woman visited our clinic after experiencing ocular discomfort in her right eye for 4 days after minor ocular trauma, with soil exposure. DIAGNOSES: Scedosporium species was isolated from a culture of corneal tissue, Scedosporium aurantiacum was identified in a culture of necrotic tissue. INTERVENTIONS: She was started on treatment with antifungal agents, including topical amphotericin B and systemic fluconazole, but her ocular condition did not improve. Although the lesion showed temporary improvement, ocular pain and corneal ulcer recurred 3 months later. Evisceration was performed due to corneal perforation, and enucleation was also performed for dehiscence of the conjunctiva and scleral necrosis. OUTCOMES: After enucleation, postoperative systemic voriconazole treatment controlled the infection without recurrence. LESSONS: S aurantiacum keratitis is difficult to eradicate, even with several months of treatment with systemic and topical antifungal agents, and tends to progress to scleritis. The infection can be terminated by the orbital enucleation. Infection with this rare organism should be included in the differential diagnosis of patients with severe infectious keratitis.

Redirecting an Anticancer to an Antibacterial Hit Against Methicillin-Resistant Staphylococcus aureus.

YM155 is a clinically evaluated anticancer with a fused naphthoquinone-imidazolium scaffold. In this study, we demonstrated that based on weak or cryptic antibacterial activity of YM155 against methicillin-resistant Staphylococcus aureus (MRSA) (MIC of 50 µg/ml), some congeneric compounds with short alkyl chains (e.g., c5 with a hexyl chain) at the N3 position of the scaffold, displayed more potent antibacterial activity against MRSA (MIC of 3.13 µg/ml), which is in a clinically achievable range. Their antibacterial activity was evident against Gram-negative bacteria, only in the presence of the outer membrane-permeabilizing agent, polymyxin B. The antibacterial efficacy of c5 was confirmed using the Drosophila systemic infection model. We also characterized five spontaneous c5-resistant MRSA mutants that carry mutations in the ubiE gene, for quinone metabolism and respiratory electron transfer, and subsequently exhibited reduced respiration activity. The antibacterial activity of c5 was compromised either by an antioxidant, N-acetylcysteine, or in an anaerobic condition. These suggest that the antibacterial mechanism of c5 involves the generation of reactive oxygen species (ROS), presumably during respiratory electron transport. This study provides an insight into "drug redirecting," through a chemical modification, based on an ROS-generating pharmacophore.

Effect of Nd:YAG Laser Capsulotomy on Anterior Segment Parameters in Patients with Posterior Capsular Opacification after Phacovitrectomy.

PURPOSE: To compare changes in anterior segment parameters after Nd:YAG laser capsulotomy in eyes that underwent either combined phacovitrectomy or cataract surgery. METHODS: This retrospective study enrolled 37 eyes of 35 patients with posterior capsular opacification treated with combined phacovitrectomy (group A), and 35 eyes of 32 patients with posterior capsular opacification treated with cataract surgery (group B). Anterior segment parameters, including anterior chamber depth (ACD), anterior chamber angle, and anterior chamber volume, were measured by a Pentacam before Nd:YAG laser capsulotomy and 1 hour, 1 day, 1 week, 1 month, and 3 months after this treatment. RESULTS: In the cataract surgery group, the ACD was significantly lower 1 day (3.75 ± 0.74 mm), 1 week (3.73 ± 0.24 mm), and 3 months (3.74 ± 0.33 mm) after Nd:YAG laser capsulotomy compared with the pretreatment value (4.20 ± 0.62 mm, p = 0.002). By contrast, the ACD did not change significantly over time in the combined phacovitrectomy group. The ACD differed significantly between the two groups at 1 week, 1 month, and 3 months after capsulotomy. There were no significant changes in the anterior chamber volume, anterior chamber angle, central corneal thickness, or pupil size from before to after capsulotomy in either group. A non-significant trend toward myopic shift was observed in group A (p = 0.072) and B (p = 0.055). CONCLUSIONS: The results of the present study may help determine the power of the intraocular lens in patients who underwent combined surgery or cataract surgery and who will receive Nd:YAG laser capsulotomy.

Extensive Submacular Hemorrhage After Trabeculectomy With Mitomycin C.

PURPOSE: We report the occurrence of an extensive submacular hemorrhage after trabeculectomy with mitomycin C in a patient with an occult choroidal neovascular membrane (CNVM). PATIENTS AND METHODS: A 66-year-old man had a 3-year history of primary open-angle glaucoma in the left eye, which had been treated with topical antiglaucoma medication. The patient had age-related macular degeneration with an occult CNVM, for which he had received 5 intravitreal injections of ranibizumab and 5 intravitreal injections of bevacizumab in the left eye over a 3-year period. As intraocular pressure was not under control in the left eye over a 2-month period, trabeculectomy with mitomycin C was performed. RESULTS: On the first postoperative day, intraocular pressure was 8 mm Hg with a well-formed bleb in the left eye. However, extensive subretinal hemorrhage was observed, and the patient underwent pneumatic displacement and pars plana vitrectomy to remove the hemorrhage. After 7 months, extensive subretinal fibrosis was observed and visual acuity was low (hand movement only). CONCLUSIONS: To our knowledge, this is the first report of an extensive submacular hemorrhage after trabeculectomy with mitomycin C in a patient with an occult CNVM.

Ascorbic acid concentrations in aqueous humor after systemic vitamin C supplementation in patients with cataract: pilot study.

BACKGROUND: To measure ascorbic acid concentration in aqueous humor of patients with cataract after oral or intravenous vitamin C supplementation. METHODS: Forty-two eyes of 42 patients with senile cataract who underwent uncomplicated cataract surgery were enrolled. Patients (n = 14 each) were administered oral vitamin C (2 g), intravenous vitamin C (20 g) or no treatment (control group) on the day before surgery. Samples of aqueous humor (0.1 cm3) were obtained by anterior chamber aspiration at the beginning of surgery and stored at -80 °C. Ascorbic acid concentration in aqueous humor was measured by high-pressure liquid chromatography. RESULTS: The mean age at surgery was 62.5 years, with no difference among the three groups. The mean ± standard deviation concentrations of ascorbic acid in aqueous humor in the control and oral and intravenous vitamin C groups were 1347 ± 331 µmol/L, 1859 ± 408 µmol/L and 2387 ± 445 µmol/L, respectively. Ascorbic acid concentration was significantly lower in the control than in the oral (P < 0.01) and intravenous (P < 0.001) vitamin C groups and was significantly higher in the intravenous than in the oral vitamin C group (P < 0.05). CONCLUSIONS: Ascorbic acid concentration in aqueous humor is increased by systemic vitamin C supplementation, with intravenous administration being more effective than oral administration.

Sub-lethal pharmaceutical hazard tracking in adult zebrafish using untargeted LC-MS environmental metabolomics.

Antibiotics in the aquatic environment are dispersed through anthropogenic activities at low concentrations. Despite their sub lethal concentration, these biologically active compounds may still have adverse effects to non-target species. This study examined the response of adult zebrafish to 0.1mg/L concentration of clarithromycin, florfenicol, sulfamethazine, and their mixture using environmental metabolomics. Embryo and larvae of the fish were also used to assess fish embryo acute toxicity and behavior tests respectively. The fish embryo toxicity test did not show any inhibition of growth and development of the embryos after 96h of exposure to the antibiotics. Changes in swimming activity were seen in 5-dpf larvae which is believed to be correlated with the length of exposure to the compounds. Meanwhile, environmental metabolomics revealed diverse metabolites and pathways that were affected after 72h of exposure of the adult fish to sub-lethal concentration of the compounds. We found that even at low concentration of the antibiotics, behavioral and metabolic effects were still observed despite the lack of visible morphological changes. Further studies involving other aquatic organisms and bioactive compounds are encouraged to strengthen the findings presented in this novel research.

Efficacy of fixed-dosing aflibercept for treating polypoidal choroidal vasculopathy: 1-year results of the VAULT study.

PURPOSE: To investigate fixed-dosing aflibercept for treating polypoidal choroidal vasculopathy (PCV). METHODS: This phase IV, prospective, single-arm, interventional case series was conducted in eight centers. Forty treatment-naïve PCV patients were administered three monthly doses of intravitreal aflibercept (2.0 mg) and an injection every 2 months thereafter. Best-corrected visual acuity (BCVA) and central subfield macular thickness (CSMT) were measured at each visit. Fluorescein and indocyanine green angiography (ICGA) were performed at baseline, 3 and 12 months. The primary outcome measure was the proportion of patients who maintained BCVA (<15 letters loss) at 12 months. Changes in BCVA, macular appearance, and polypoidal lesion appearance were also examined. RESULTS: Thirty-five eyes (87.5 %) had maintained BCVA at 12 months. Average BCVA was significantly higher at 12 months (20/53, 64.2 letters) than at baseline (20/80, 55.1 letters, 9-letter gain; P < .001). Mean CSMT was significantly lower at 12 months (253.6 µm) than at baseline (365.2 µm, P < .001). The macula was dry in 32 (76.2 %), 27 (64.3 %), and 24 eyes (60.0 %) at 3, 6, and 12 months respectively. Fourteen eyes (33.3 %) had a fluid recurrence or increase at 6 months, and they had a significantly lower vision gain (P = .005) than other patients at 12 months. Complete polyp regression occurred in 26 eyes (66.7 %) at 12 months. CONCLUSIONS: Fixed-dosing aflibercept showed favorable outcomes in PCV patients at 12 months. However, some patients had worse outcomes because of fluid recurrence during maintenance dosing, and these patients would require additional treatments.