Rubens Belfort’s research while affiliated with Federal University of São Paulo and other places

Background We used state-of-the-art high-resolution retinal imaging to explore the treatment (loading dose of aflibercept) of diabetic macular edema (DME) among treatment-naive patients. Swept-source (SS) OCT and OCT-Angiography (SS-OCTA) were performed, and a dichotomous analysis was conducted to compare responders and treatment-resistant patients (responsive and resistant). Furthermore, treatment responses were evaluated based on the subdivision of choroidal thickness. Materials and methods This prospective, noncomparative, interventional case series study examined the following biomarkers: best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), avascular area of the superficial plexus (AASP), avascular area of the deep plexus (AADP), and vessel density (VD). Data from the baseline and 4-month examinations were compared. Results Twenty-eight eyes from 25 patients were included. Significant improvements were observed in BCVA (0.7250 ± 0.23 to 0.3957 ± 0.21; p < 0.000), CMT µm (339.04 ± 66.19 to 265.21 ± 55.75; p < 0.000), CCT µm (221.71 ± 69.69 to 209.07 ± 70.92; p < 0.000), VD (17.90 ± 7.82 to 15.35 ± 5.80; p < 0.038), AASP µm ² (235,374 ± 91,299 to 157,326 ± 77,815; p < 0.000) and AADP µm ² (996,335 ± 1,000,047 to 362,161 ± 277,225; p < 0.000). Dichotomous analysis revealed that 15 patients were responsive (53.57%), and 13 resistant (46.43%). There were no significant differences between any of the pretreatment biomarkers. In the subdivision of choroidal thickness, which ranged from 211 to 270 µm (group 3), we found greater reductions in the CCT, AADP and CD. The choroidal thickness ranged from 181 to 210 µm (group 2): BCVA and AASP exhibited the greatest reductions. Conclusion BCVA, CMT, CCT, AASP, AADP and VD were improved after treatment. The pretreatment biomarkers did not predict treatment response between the responsive and resistant. Regarding choroidal stratification, values within the normal range of CCT showed the greatest reductions, indicating that these values may be more responsive to treatment. Notably, this is the first study to analyze biomarkers provided by SS OCT and OCTA, stratify the choroid, and perform a dichotomous analysis.

Purpose: This study compares the performance of two no-code machine learning platforms, Google's Teachable Machine (TM) (Google LLC, Mountain View, CA, USA) and Apple's Create ML (Apple Inc., Cupertino, CA, USA), alongside a traditional deep learning model, ResNet200d, in classifying optic nerve fundus images into glaucoma and non-glaucoma categories using the ACRIMA dataset. Methods: A comparative cross-sectional analysis was conducted using 705 labeled fundus images from the ACRIMA dataset (326 glaucomatous, 239 non-glaucomatous). Models were trained separately on each platform, and a validation set comprising 70 glaucomatous and 70 non-glaucomatous images was used to assess performance. Performance metrics, such as sensitivity, specificity, F1 score, and Cohen's kappa, were assessed with 95% confidence intervals. Statistical analysis was performed using DATAtab (DATAtab e.U. Graz, Austria (https://datatab.net)). Results: The ResNet200d model demonstrated the highest performance, with an accuracy of 99.29%, a sensitivity of 98.57%, a specificity of 100%, and an F1 score of 99.29%. Create ML achieved a sensitivity of 93.24%, a specificity of 98.48%, and an F1 score of 95.83%. TM exhibited a sensitivity of 95.71%, a specificity of 94.29%, and an F1 score of 95.04%. Both no-code platforms demonstrated strong performance, with Create ML excelling in specificity and TM showing higher sensitivity. Conclusion: While the ResNet200d model outperformed both no-code platforms in diagnostic accuracy, the no-code platforms demonstrated robust capabilities, highlighting their potential to democratize artificial intelligence (AI) in healthcare. These results highlight the potential of no-code platforms for democratizing medical image analysis, especially in resource-limited contexts. Further studies with diverse datasets are recommended to validate these results.

Corneal diseases represent a significant cause of blindness worldwide, with corneal transplantation being an effective treatment to prevent vision loss. Despite substantial advances in transplantation techniques, the demand for donor corneas exceeds the available supply, particularly in developing countries. Cornea xenotransplantation has emerged as a promising strategy to address the worldwide scarcity, notably using porcine corneas. In addition to the inherent immune privilege of the cornea, the low cost of porcine breeding and the anatomical and physiological similarities between humans and pigs have made porcine corneas a viable alternative. Nonetheless, ethical concerns, specifically the risk of xenozoonotic transmission and the necessity for stringent biosafety measures, remain significant obstacles. Moreover, the success of xenotransplantation is compromised by innate and adaptive immune responses, which requires meticulous consideration and further studies. Despite these challenges, recent breakthroughs have further contributed to reducing immunogenicity while preserving the corneal architecture. Advances in genetic engineering, such as the use of CRISPR-Cas9 to eliminate critical porcine antigens, have shown promise for mitigating immune reactions. Additionally, new immunosuppressive protocols, such as have techniques like decellularization and the use of porcine-derived acellular matrices, have greatly increased graft survival in preclinical models. Future research must focus on refining immunomodulatory strategies and improving graft preparation techniques to ensure the long-term survival and safety of porcine corneal xenotransplantation in clinical trials in humans.

Purpose To characterize the extracellular vesicle protein cargo in the aqueous humor and plasma of patients with ocular toxoplasmosis. Methods Aqueous humor and plasma were collected from six patients with active ocular toxoplasmosis and six patients with cataract. Extracellular vesicles were isolated, and western blotting and mass spectrometry were performed for protein analysis. Results All plasma samples from patients with ocular toxoplasmosis and cataract were positive for the tetraspanins CD63 and TSG101. However, the aqueous humor from patients with ocular toxoplasmosis was positive only for CD63. Sixty-seven new unreported proteins were identified in the aqueous humor and plasma of patients with the ocular toxoplasmosis and cataract. Of the 67 proteins, 10 and 7 were found only in the cataract and ocular toxoplasmosis groups, respectively. In general, these proteins were involved in immune system activation and retina homeostasis and were related to infections and retina-associated diseases. Conclusion The distinct protein signatures between ocular toxoplasmosis and cataract may be helpful in the differential diagnosis of ocular toxoplasmosis. However, more studies are needed to better understand the role of these proteins in the pathogenesis of ocular toxoplasmosis. Keywords: Extracellular vesicles; Proteomics; Toxoplasma gondii ; Ocular toxoplasmosis; Aqueous humor; Plasma; Liquid biopsy

Ocular syphilis is a re-emerging inflammatory eye disease with a clear gender imbalance, disproportionately affecting men. We investigated the impact of gender on the presentation, management practices and clinical outcomes of this condition. Data generated from a study of patients consecutively diagnosed with ocular syphilis who attended a subspecialist uveitis service at one of four hospitals in Brazil over a 30-month period were disaggregated for analysis by gender. Two-hundred and fourteen eyes (161 men and 53 women) of 127 patients (96 men and 31 women) were included. Posterior uveitis was the most common presentation in both men and women (80.1% vs. 66.7%, p > 0.05), but men were significantly more likely to have vitritis as a feature of their disease (49.4% versus 28.8%, p = 0.019). Three eyes of women had nodular anterior scleritis (p = 0.015). Men were more likely to undergo a lumbar puncture to assess for neurosyphilis (71.9% vs. 51.6%, p = 0.048), but men and women undergoing a lumbar puncture were equally likely to have a cerebrospinal fluid abnormality (36.2% vs. 25.0%, p = 0.393). All patients were treated with aqueous penicillin G or ceftriaxone, and there was a trend towards more men receiving adjunctive systemic corticosteroid treatment as part of their management (65.2% vs. 46.7%, p = 0.071). There were no significant differences in the age of presentation, bilaterality of disease, anatomical classification of uveitis, initial or final visual acuity, and rates of ocular complications between men and women. Our findings indicate that ocular syphilis has comparable outcomes in men and women, but that there are differences in the type of ocular inflammation and management practices between the genders.

Purpose: To demonstrate that the presence of active retinochoroiditis in eyes with previous hyperpigmented old retinochoroidal lesions is not exclusive of ocular toxoplasmosis. Methods: A case series was constructed by reviewing medical records. Results: Four Brazilian patients presenting active posterior uveitis in eyes with previous hyperpigmented old retinochoroidal lesions were identified. Ocular toxoplasmosis was ruled out in all cases. One case had viral etiology confirmed through vitreous PCR (HSV-2 was positive), and the other 3 cases had a presumed diagnosis of herpetic posterior uveitis. Conclusion: Focus active retinitis adjacent to an old cicatricial lesion should not be considered pathognomonic of toxoplasmosis and viral etiology must be considered.

Purpose: To report a challenging case of serologically confirmed posterior uveitis due to leptospirosis. Methods: Review of medical records. Results: Thirteen-year-old boy presented focal necrotizing retinochoroiditis after flood exposure. Laboratory work-up confirmed leptospirosis infection and proper antibiotic treatment was done. The patient evolved well. but during late follow-up he developed nummular keratitis. Conclusion: Leptospirosis is a possible etiology of necrotizing posterior uveitis. The use of antimicrobial therapy is controversial but was used in this case, in association with corticosteroids, leading to resolution of retinal inflammation. Despite treatment, the patient developed late corneal opacities, which did not lead to visual impairment.

Objective To evaluate the epidemiological, clinical, and imaging profile of lesions that mimic choroidal melanoma. Methods Retrospective study of medical records of suspected choroidal melanoma lesions referred to the Ocular Oncology Service from the Universidade Federal de São Paulo, from 2014 to 2020. Demographic data, clinical history, and exams were evaluated. Results A total of 104 patients (mean age: 65.57 ± 13.18; 49.04% female) were referred to our service with suspected choroidal melanoma. Of these, 32 (30.77%) were classified as pseudomelanoma, while 72 (69.23%) had a confirmed diagnosis of choroidal melanoma. Pseudomelanoma cases manifested in older individuals (p < 0.001), with smaller lesions in height (p < 0.001), anteroposterior diameter (p = 0.008), and lateral diameter (p = 0.003) on ultrasound. Pseudomelanoma cases were associated with higher frequencies of vitreous hemorrhage (p = 0.014) and lower rates of the presence of a mass (p = 0.001) and retinal detachment (p < 0.001). The main diagnoses of pseudomelanoma cases were choroidal nevus (40.63%), subretinal hemorrhage (18.75%) and choroidal neovascular membrane (18.75%). Conclusion Almost one third of the cases referred with suspected choroidal melanoma were pseudomelanomas, which demonstrates that there is still a considerable path to improve the ability of general ophthalmologists to clinically discriminate melanoma from other conditions that can mimic it. Keywords: Melanoma; Choroid neoplasms; Epidemiology

The purpose of the study was to present a case of choroidal neovascularization (CNV) in unilateral acute idiopathic maculopathy (UAIM) associated with coxsackievirus B2. We present a case of UAIM with coxsackie B2 positive serology, presenting CNV as a complication. Follow-up multimodal retinal imaging was performed to characterize the macular abnormalities further. A 27-year-old woman complained of a sudden central visual field scotoma in her left eye (LE) 2 days before her presentation. The patient reported flu-like symptoms 2 weeks before her initial ophthalmic symptoms. Ophthalmologic examination and multimodal imaging were performed at the initial presentation and 2 months follow-up when CNV was detected. The patient underwent an intravitreous ranibizumab injection in the LE. After the injection, the optical coherence tomography was repeated and there was a partial decrement of the subretinal hyperreflective area, and visual acuity improved to 20/30. To the best of our knowledge, no previous reports were found linking coxsackie B2 infection with UAIM and CNV. The present case report demonstrates the importance of serial multimodal imaging to guarantee accurate diagnosis and effective therapy for patients with UAIM secondary to coxsackievirus infection, regardless of the virus variant involved.