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Background: Age-related macular degeneration (AMD) is a leading cause of vision loss. Photobiomodulation (PBM) offers a controversial approach for managing dry AMD, aiming to halt or reverse progression through mitochondrial activity modulation. However, the efficacy and clinical relevance of PBM as a potential approach for managing dry AMD remain debated. Methods: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing PBM versus a sham in patients with dry AMD. We performed trial sequential analysis (TSA) and minimal clinically important difference (MCID) calculations to assess statistical and clinical significance applying a random-effects model with 95% confidence intervals (CI). Results: We included three RCTs comprising 247 eyes. The pooled analysis showed that PBM significant improved BCVA (MD 1.76 letters; 95% CI: 0.04 to 3.48) and drusen volume (MD -0.12 mm³; 95% CI: -0.22 to -0.02) as compared with a sham control. However, the TSA indicated that the current sample sizes were insufficient for reliable conclusions. No significant differences were observed in GA area. The MCID analysis suggested that the statistically significant results did not translate into clinically significant benefits. In the quality assessment, all studies were deemed to have a high risk of bias. Conclusion: This meta-analysis points limitations in the current evidence base for PBM in dry AMD treatment, with issues around small sample sizes. Statistically significant improvements do not translate into clinical benefits. The research underscores need for larger RCTs to validate PBM's therapeutic potential for dry AMD. [ABSTRACT FROM AUTHOR]

Purpose: To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may influence pain sensitivity. Methodology: This is a prospective, observational, case series study involving patients who underwent multiple (≥ 3) pro re nata intravitreal injections of ranibizumab or aflibercept to treat any cause of chorioretinal vascular disease. Ocular pain was assessed by the numerical analog scale during intravitreal injection. For this study, the main variable was ocular pain and the secondary variables included age, sex, previous history of glaucoma, primary retinal vascular disease, severe dry eye history, trigeminal pain, scleral buckle surgery, collagen diseases, fibromyalgia, severe migraine history, pars plana vitrectomy, scleral thickness measurements, and type of anti-VEGF. Results: In a total of 894 patients, 948 eyes (4822 intravitreal injections), 793 patients (88.6%) had ocular pain sensitivity between no pain to mild pain, 80 patients (8.9%) had moderate ocular pain, 15 patients (1.6%) had severe ocular pain, and 6 patients (0.7%) had extremely severe ocular pain. Patients with severe dry eye (p = 0.01) and previous history of scleral buckle surgery (p = 0.01) showed a significant correlation with ocular pain during intravitreal injection. Pars plana scleral thickness (> 550 um) and diabetic neuropathy were associated with ocular pain but did not meet the criteria for statistical significance (p = 0.09 and p = 0.06, respectively). Conclusion: Dry eye and prior scleral buckle surgery may contribute to pain associated with intravitreal injection. These issues should be taken into consideration in patients undergoing multiple intravitreal injections. [ABSTRACT FROM AUTHOR]

Background: Describe complications and clinical outcomes of heavy silicone oil (HSO) Oxane HD® use as an alternative to overcome the challenges of performing vitrectomy to treat tractional and rhegmatogenous retinal detachments with proliferative vitreoretinopathy (PVR). Methods: A retrospective, observational study was performed on patients from one center from August 2014 to Aug 2023. It was included patients who underwent surgery using HSO Oxane HD® to treat rhegmatogenous retinal detachment with PVR or mixed tractional and rhegmatogenous diabetic retinal detachment. Severely ill patients who could not attend to follow up were excluded. The primary outcome was successful retinal attachment at first postoperative month. A descriptive analysis was performed. Results: Among the 31 patients, 29 (93.5%) underwent surgeries due to rhegmatogenous retinal detachment and two (6.5%) for diabetic retinal detachment. The primary anatomic success was achieved in 27 (87.1%) patients. At the final visit, 17 (56.6%) had vision better than 20/400 (range, 20/30 to light perception). The vision was stable or improved in 22 (76.8%) patients at the end of follow-up. Nineteen (61.3%) patients required hypotensive eye drops after HSO use and twelve (38.7%) still required hypotensive eye drops at the final follow-up; three (9.7%) patients required additional glaucoma surgeries. Conclusions: HSO is safe and useful for complex retinal detachments cases specially with inferior tears and PVR. Ocular hypertension is frequent and usually clinically controlled with hypotensive eyedrops. Close postoperatively follow-up is advised due to the ocular complications, particularly elevated intraocular pressure and emulsification. [ABSTRACT FROM AUTHOR]

The port delivery system with ranibizumab (PDS) is designed to continuously deliver ranibizumab to maintain therapeutic drug concentrations in the vitreous of the eye for an extended duration. The PDS has been evaluated for the treatment of neovascular age‐related macular degeneration in the Ladder (PDS 10, 40, and 100 mg/mL, with refill exchanges as needed, versus monthly intravitreal ranibizumab 0.5 mg), Archway (PDS 100 mg/mL with 24‐week refill exchanges, versus monthly intravitreal ranibizumab 0.5 mg), and ongoing Portal (PDS 100 mg/mL with 24‐week refill exchanges) clinical trials. Data from Ladder, Archway, and Portal were used to develop a population pharmacokinetics (PK) model to estimate the ranibizumab release rate from the PDS implant, describe ranibizumab PK in serum and aqueous humor, and predict the concentration in vitreous humor. A model was developed to adequately describe the serum and aqueous humor PK data, as suggested by goodness‐of‐fit plots as well as visual predictive checks. In the final model, the first‐order implant release rate was estimated to be 0.00654 (1/day), corresponding to a half‐life of 106 days, consistent with the implant release rate determined in vitro. The model‐predicted vitreous concentrations achieved with PDS 100 mg/mL given every 24 weeks were below the intravitreal peak concentration and above the intravitreal trough concentration of ranibizumab over the entire 24‐week refill interval. The results demonstrate a durable release of ranibizumab from the PDS with a half‐life of 106 days, providing vitreous exposure to ranibizumab for at least 24 weeks that is within the range of exposure for monthly intravitreal treatment. [ABSTRACT FROM AUTHOR]

aime Soria,5 Valentina Franco-Cárdenas,6 Victor E Reviglio,7 Paulo EC Dantas,8 Claudia Palacio Pastrana,9 Juan Carlos Corbera,10 Rita Yee Chan,11 Alberto Luis Diaz,12 Milton Garcia Hernandez,13 Mauricio Maia,14 Cristian Carpentier,15 Lihteh Wu,16 Martin Sanchez,17 Marcelo Murillo Sasamoto,18 Gonzalo Murillo Azcárraga,18 Jose A Roca,19 Martin A Serrano,20 Arturo A Alezzandrini,21 Juan Gonzalo Sanchez Montoya,22 Gregorio Gabela,23 Gerardo Garcia-Aguirre,24 J Fernando Arevalo25,*1Fundación Somos Ciencia al Servicio de la Comunidad, Fundación SCISCO/Science to Serve the Community Foundation, SCISCO Foundation, Cali, Colombia; 2Ophthalmology Department, Institute for Clinical Research Education, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; 3Vision y Salud Ocular, VISOC, Ophthalmology Department, Universidad del Valle, Cali, Colombia; 4The Retina and Vitreous Department, Private Eyes Clinic, Mar del Plata, Argentina; 5Ophthalmology Department, Clínica Real Visión, Uniofken, CIVE y Funcrisa, Guayaquil, Ecuador; 6Ophthalmology Department, Sanatorio Oftalmológico Mérida, Mexico City, Mexico; 7Ophthalmology Department, Instituto de la Visión Cerro, Sanatorio Allende Cerro & Universidad Católica de Córdoba, Health Science Faculty, Cordoba, Argentina; 8Ophthalmology Department, Sorocaba Eye Bank Hospital, Sorocaba, Brazil; 9Department of Microsurgery of the Anterior Segment, Fundación Hospital Nuestra Señora de la Luz IAP, Mexico City, Mexico; 10Ophthalmology Department, Oftalmica Clinica de la Vision, Lima, Peru; 11Ophthalmology Department, Clinica Nacional de Oftalmologia, Panama City, Panama; 12Ophthalmology Department, Complejo Medico FOSCAL Internacional, Floridablanca, Santander, Colombia; 13Ophthalmology Department, Private Practice, El Salvador, El Salvador; 14Ophthalmology Department, Federal University of Sao Paulo, Sao Paulo, Brazil; 15Ophthalmology Department, Fundación Oftalmológica Los Andes, Santiago, Chile; 16Retina Department, Asociados de Macula Vitreo y Retina de Costa Rica, San Jose, Costa Rica; 17Ophthalmology Department, Hospital de Minas, Montevideo, Uruguay; 18Ophthalmology Department, Instituto Privado de Oftalmología, La Paz, Bolivia; 19Ophthalmology Department, Universidad Peruana Cayetano Heredia, Lima, Peru; 20Retina Department, Centro Médico Docente La Trinidad, Caracas, Venezuela; 21Ophthalmology Department, OFTALMOS, Universidad de Buenos Aires, Facultad de Medicina, Buenos Aires, Argentina; 22Ophthalmology Department, Instituto Nacional de Investigacion en Oftalmologia –INIO and Clinica Oftalmologica de Antioquia, Medellin, Colombia; 23Ophthalmology Department, Hospital Metropolitano, Quito, Ecuador; 24Retina Department, School of Medicine, Tecnológico de Monterrey Asociación Para Evitar la Ceguera en México, Mexico City, Mexico; 25Ophthalmology Department, Johns Hopkins University, Wilmer Eye Institute, Baltimore, MD, USA*These authors contributed equally to this workCorrespondence: J Fernando Arevalo, Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Maumenee 713, Baltimore, MD, 21287, USA, Email [email protected] Purpose: The COVID-19 pandemic affected medical practice worldwide due to interventions to prevent spreading. Its effect on ophthalmology practices in Latin America has not yet been explored. We aimed to assess the perceptions about the pandemic from countries' ophthalmological national and subspecialty retina societies affiliated to the Pan-American Association of Ophthalmology (PAAO).Patients and Methods: A survey-based study of leaders of national ophthalmological and retinal societies was conducted. The survey was sent by email to 30 societies, from which 20 responded (12 countries, 66.6% response rate). It included closed- and open-ended questions about (1) operational capacity and precautions, (2) telemedicine and virtual care, (3) procedures, and (4) post-pandemic considerations.Results: There was a marked decline in ophthalmology patient visits (80– 95%) and elective surgeries (90%) during 2020 compared to before the pandemic. Precautions like temperature checks, mask usage, and social distancing were widely implemented while personal protective equipment (PPE) availability varied. Telemedicine use was limited due to lack of experience with it. Reopening plans focused on maintaining precautions and gradually resuming activities. Economic and security concerns were raised, and adherence to guidelines was emphasized. Respondents acknowledged the need to adapt to a "new normal". Long duration drugs, fewer imaging studies, and shorter wait times were preferred; however, availability of long duration drugs was limited.Conclusion: The pandemic impacted ophthalmology in Latin America, with reduced patient visits, procedures, and surgeries. Delayed treatment and complications were likely the result of the pandemic. [ABSTRACT FROM AUTHOR]

The main drawback for the use of heavy silicone oil (HSO) Oxane HD is the difficulties it presents during removal. It differs from conventional silicone oil removal because it progressively concentrates in the posterior pole during the removal because of its heavier than water density. We describe a technique to facilitate proper HSO Oxane HD removal and minimize residual posterior bubbles and intraoperative complications. We describe our pearls for removing HSO to obtain the optimal results. A concern associated with HSO is the difficulty it presents when it is removed. However, this can be overcome by appropriate modification of surgical techniques during removal to limit intraoperative complications. [ABSTRACT FROM AUTHOR]

Advances in vitreoretinal surgery provide greater safety, efficacy, and reliability in the management of the several vitreoretinal diseases that benefit from surgical treatment. The advances are divided into the following topics: scleral buckling using chandelier illumination guided by non-contact visualization systems; sclerotomy/valved trocar diameters; posterior vitrectomy systems and ergonomic vitrectomy probes; chromovitrectomy; vitreous substitutes; intraoperative visualization systems including three-dimensional technology, systems for intraoperative optical coherence tomography, new instrumentation in vitreoretinal surgery, anti-VEGF injection before vitrectomy and in eyes with proliferative diabetic retinopathy, and new surgical techniques; endoscopic surgery; the management of subretinal hemorrhages; gene therapy; alternative techniques for refractory macular hole; perspectives for stem cell therapy and the prevention of proliferative vitreoretinopathy; and, finally, the Port Delivery System. The main objective of this review is to update the reader on the latest changes in vitreoretinal surgery and to provide an understanding of how each has impacted the improvement of surgical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Ladder was a phase 2 trial that evaluated the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration. Serum and aqueous humor samples were collected to characterize the pharmacokinetics (PK) of ranibizumab delivered through the PDS. Methods: Ladder was a multicenter, randomized, active treatment-controlled, phase 2 clinical trial. Patients with neovascular age-related macular degeneration (n = 220) were randomized (3:3:3:2) to PDS 10 mg/ml, PDS 40 mg/ml, PDS 100 mg/ml, or monthly intravitreal ranibizumab 0.5 mg. Serum PK samples were collected in all arms and analyzed for ranibizumab concentration using an enzyme-linked immunosorbent assay. The main PK analyses were conducted in the PK-evaluable population (n = 68), which excluded patients who received fellow eye intravitreal treatment, supplemental ranibizumab treatment, or had previous treatment with bevacizumab in either eye within 9 months of randomization. Results: In the PDS 10 mg/ml arm, median serum ranibizumab concentrations were below the serum trough concentration (Ctrough; 130 pg/ml) expected with monthly intravitreal ranibizumab 0.5 mg at all time points. In the PDS 40 mg/ml and 100 mg/ml arms, median serum ranibizumab concentrations were above the Ctrough expected with monthly intravitreal ranibizumab 0.5 mg (130 pg/ml) through month 3 and month 12 after implantation, respectively, and remained above the lower limit of quantification through month 15 and month 16 after implantation, respectively. Conclusions: These PK data indicate that the implant in the PDS 100 mg/ml arm maintained ranibizumab concentrations within the range of monthly intravitreal ranibizumab 0.5 mg injections (130–2220 pg/ml) through month 12 after implantation. Trial Registration: ClinicalTrials.gov identifier, NCT02510794. [ABSTRACT FROM AUTHOR]

Background: Noninfectious endophthalmitis may be misdiagnosed, leading to serious clinical implications. So far, its causative factors remain unknown. Therefore, this study assessed the role of silicone oil and syringe agitation in the development of inflammation after intravitreal injection of aflibercept. Methods: A randomized, double-blind, controlled clinical trial included subjects with an indication of intravitreal antiangiogenic therapy prior to vitrectomy for proliferative diabetic retinopathy. Aflibercept was injected 48 h before surgery. The control group received the injection without agitation, while the intervention group was injected with a previously agitated syringe by flicking with either a siliconized or silicone oil-free syringe. The primary endpoint was the presence of anterior chamber reaction (ACR) at 48 h. Aqueous samples were collected and underwent cytometric bead array analysis for quantification of interleukins and chemokines. Results: Forty-one individuals were included (21 in the agitation group and 20 in the no-agitation group). None of the included eyes showed baseline signs of AC cells, hyperemia or pain complaint, while 10% of control group and 80% of agitation group showed AC cells 48 h after injection of aflibercept with SR syringe. There were no differences in the mean variations of all cytokines and chemokines by agitation status. However, there was a marginally significant increase between the mean variations of IP-10 (p = 0.057) and IL-8 (p = 0.058) in the siliconized one. Conclusion: This clinical trial discloses a potential role of agitation and siliconized syringes in the development of inflammation after an intravitreal injection of aflibercept. These findings have important clinical implications for all healthcare practitioners who perform intravitreal injections. Trial Registration: Brazilian Registry of Clinical Trials, RBR-95ddhp. Registered 12 May 2019, http://www.ensaiosclinicos.gov.br/rg/RBR-95ddhp/ [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to report the 5-year outcomes of treatment-naive eyes with cystoid macular edema secondary to central retinal vein occlusion treated with intravitreal bevacizumab in routine clinical practice. Methods: We conducted multicenter retrospective non-comparative case series of 102 eyes. The main outcome measured was the change in best-corrected visual acuity (BCVA) at 5 years. Secondary outcomes included the number of injections and the change in CMT at 5 years. Results: At 5 years, the mean BCVA improved from 1.22 ± 0.58 (Snellen 20/428) at baseline to 1.00 ± 0.68 logMAR (Snellen 20/200; p < 0.0001). At 5 years, 48 (47%) eyes had a gain of ≥ 3 lines, 41 (40.2%) eyes remained within 3 lines and 13 (12.7%) eyes had a loss of ≥ 3 lines of BCVA. The CMT improved from 740 ± 243 to 322 ± 179 µm (p < 0.0001). At 5 years, 59 (57.8%) eyes had a completely dry SD-OCT. Patients received a total of 10.6 ± 6.1 (range 6–27) injections. Baseline BCVA (p < 0.0001) and the duration of symptoms prior to initial anti-VEGF injection (p = 0.0274) were the only predictive factors for BCVA at 5 years. Conclusions: After 5 years with an average of 10.6 injections, there was a mean gain of 0.22 logMAR. In addition, more eyes achieved a BCVA of ≥ 20/40, gained ≥ 3 lines and less patients had a BCVA ≤ 20/200. Eyes with a better baseline BCVA and a shorter duration of symptoms were more likely to achieve better BCVA at 5 years. [ABSTRACT FROM AUTHOR]

Background: Artificial intelligence and automated technology were first reported more than 70 years ago and nowadays provide unprecedented diagnostic accuracy, screening capacity, risk stratification, and workflow optimization. Diabetic retinopathy is an important cause of preventable blindness worldwide, and artificial intelligence technology provides precocious diagnosis, monitoring, and guide treatment. High-quality exams are fundamental in supervised artificial intelligence algorithms, but the lack of ground truth standards in retinal exams datasets is a problem. Main body: In this article, ETDRS, NHS, ICDR, SDGS diabetic retinopathy grading, and manual annotation are described and compared in publicly available datasets. The various DR labeling systems generate a fundamental problem for AI datasets. Possible solutions are standardization of DR classification and direct retinal-finding identifications. Conclusion: Reliable labeling methods also need to be considered in datasets with more trustworthy labeling. [ABSTRACT FROM AUTHOR]

FHTR2163 is an antigen-binding fragment of a humanized immunoglobulin G1 monoclonal antibody directed against high-temperature requirement A serine peptidase 1 (HTRA1) that is being developed as a potential intravitreal (ITV) treatment for patients with geographic atrophy (GA), an advanced form of dry age-related macular degeneration. The nonclinical toxicology program was designed to assess the safety and tolerability of HTRA1 inhibition following ITV administration of FHTR2163 to support ITV administration in patients with GA. FHTR2163 was well tolerated in a single-dose ITV-administered 8-day toxicity study in cynomolgus monkeys following a 50 µL high (>700 mOsm/kg) osmolality formulation up to 12.5 mg/eye; however, 100 µL (2× 50 µL injections) of a high-osmolality formulation resulted in transient retinal detachment. Repeat-dose ITV administration every 2 weeks of FHTR2163 was well tolerated in 8- and 26-week studies with ITV injection of 100 µL (2× 50 μL) of iso-osmolar formulation up to 15 mg/eye, or 50 µL of the high-osmolality formulation up to 12.5 mg/eye. Observed transient and reversible ocular effects included inflammation and perivascular infiltrates, consistent with an immune response attributed to the administration of heterologous (humanized) protein. Overall, FHTR2163 was well tolerated, and the nonclinical package supported the continued clinical development of FHTR2163 in patients with GA. [ABSTRACT FROM AUTHOR]

The Port Delivery System with ranibizumab (PDS) is an investigational drug delivery system designed to provide continuous intravitreal release of ranibizumab for extended durations. The PDS consists of a permanent, surgically placed, refillable intraocular implant; a customized formulation of ranibizumab; and ancillary devices to support surgery and refill procedures. A toxicology program was conducted to evaluate the ocular toxicology and biocompatibility of the PDS to support its clinical development program and product registrational activities. PDS safety studies included a 6-month chronic toxicology evaluation in minipigs as well as evaluation of nonfunctional surrogate implants (comprised of the same implant materials but without ranibizumab) in rabbits. Biocompatibility of the implant and ancillary devices was evaluated in both in vitro and in vivo studies. Implants and extracts from implants and ancillary devices were nongenotoxic, noncytotoxic, nonsensitizing, and nonirritating. Ocular findings were comparable between implanted and sham-operated eyes, and no systemic toxicity was observed. The results of this nonclinical toxicology program demonstrated that the PDS was biocompatible and that intravitreal delivery of ranibizumab via the PDS did not introduce any new toxicology-related safety concerns relative to intravitreal injections, supporting ongoing PDS clinical development and product registrational evaluation. [ABSTRACT FROM AUTHOR]

The proactive generation of anti-idiotypic antibodies (anti-IDs) against therapeutic antibodies with desirable properties is an important step in pre-clinical and clinical assay development supporting their bioanalytical programs. Here, we describe a robust platform to generate anti-IDs using rabbit single B cell sorting-culture and cloning technology by immunizing rabbits with therapeutic drug Fab fragment and sorting complementarity determining regions (CDRs) specific B cells using designed framework control as a negative gate to exclude non-CDRs-specific B cells. The supernatants of cultured B cells were subsequently screened for binding to drug-molecule by enzyme-linked immunosorbent assay and the positive hits of B cell lysates were selected for cloning of their immunoglobulin G (IgG) variable regions. The recombinant monoclonal anti-IDs generated with this method have high affinity and specificity with broad epitope coverage and different types. The recombinant anti-IDs were available for assay development to support pharmacokinetic (PK) and immunogenicity studies within 12 weeks from the start of rabbit immunization. Using this novel rapid and efficient in-house approach we have generated a large panel of anti-IDs against a series of 11 therapeutic antibody drugs and successfully applied them to the clinical assay development. [ABSTRACT FROM AUTHOR]

MHAA4549A is a human anti‐influenza A monoclonal antibody developed to treat influenza A. We report MHAA4549A serum, nasopharyngeal, and tracheal aspirate pharmacokinetics from a phase 2b study in hospitalized patients with severe influenza A. Patients were randomized 1:1:1 into 3 groups receiving single intravenous doses of 3600 mg (n = 55) or 8400 mg (n = 47) MHAA4549A or placebo (n = 56). Patients also received oral oseltamivir twice daily for ≥5 days. Serum, nasopharyngeal, and tracheal aspirate pharmacokinetic samples were collected on days 1‐60 from MHAA4549A‐treated groups. Day 5 plasma samples from all groups were collected for assessing the pharmacokinetics of oseltamivir and its active metabolite, oseltamivir carboxylate. Noncompartmental pharmacokinetic analysis was performed using Phoenix WinNonlin. Data were collected during a preplanned interim analysis that became final when the trial terminated because of a lack of efficacy. Serum MHAA4549A concentrations were dose‐proportional and biphasic. Mean MHAA4549A clearance was 288‐350 mL/day, and mean half‐life was 17.8‐19.0 days. Nasopharyngeal MHAA4549A concentrations were non‐dose‐proportional. We detected MHAA4549A in tracheal aspirate samples, but intersubject variability was high. MHAA4549A serum and nasopharyngeal exposures were confirmed in all MHAA4549A‐treated patients. Serum MHAA4549A had faster clearance and a shorter half‐life in influenza A‐infected patients compared with healthy subjects. MHAA4549A detection in tracheal aspirate samples indicated exposure in the lower respiratory tract. Oseltamivir and oseltamivir carboxylate exposures were similar between MHAA4549A‐treated and placebo groups, suggesting a lack of MHAA4549A interference with oseltamivir pharmacokinetics. [ABSTRACT FROM AUTHOR]

Purpose: To report our experience in non-contact wide-angled visualization with chandelier-assisted scleral buckling (SB) in uncomplicated primary rhegmatogenous retinal detachments (RRD). Methods: Retrospective case series of 282 eyes that underwent non-contact wide-angled visualization with chandelier-assisted SB and were followed for a mean of 13.5 months. Results: There were 160 male patients. The average age was 42.6 years old. There were 262 eyes that were phakic, 18 pseudophakic, and 2 aphakic. Two-thirds of eyes presented with the macula detached. Eyes had an average of 1.6 breaks. The single operation anatomic success rate was 85.1% (240/282). The pre-op visual acuity improved from 1.21 to 0.76 logMAR at 6 months (p < 0.0001). Complications included a case of scleral laceration, choroidal hemorrhage, 3 epiretinal membranes, 1 macular fold, and 4 eyes with buckle exposure. Conclusion: Non-contact wide-angled visualization with chandelier-assisted SB compares favorably with conventional SB for primary uncomplicated primary RRD. [ABSTRACT FROM AUTHOR]

Background: Many factors can influence the functional outcomes of macular hole surgery and some studies have tried to describe anatomical features that could predict successful treatment. The purpose of this study is to describe a new technique for evaluating the healing of macular holes after two surgical techniques using a black-and-white pixel binarization histogram software by optical coherence tomography angiography and its potential functional implications. Methods: This was a retrospective, observational case series of patients who presented with idiopathic full-thickness macular holes and underwent vitreoretinal surgery for successful macular hole closure using the internal limiting membrane peeling technique or the inverted peeling technique or the free internal limiting membrane flap technique. Optical coherence tomography angiography 3.0 × 3.0-mm scans were obtained postoperatively. The outer retina layer was analyzed separately; three different analyses were performed within a 3.0-mm-diameter area central circle, a 1.5-mm-diameter area, and a 0.5-mm-diameter area from the foveal center. The outer retinal layer images were evaluated by counting the number of black and white pixels. The inclusion criteria were patients with idiopathic macular holes who underwent ophthalmologic examinations and swept-source optical coherence tomography 1 week and 1 and 6 months postoperatively. The exclusion criteria were a traumatic macular hole or a history of eye trauma and a diagnosis of glaucoma or any other chronic ocular disease. The Mann–Whitney test was used to determine significance; P < 0.05 was considered significant. Results: Ten eyes of 10 patients who underwent vitreoretinal surgery to treat a macular hole either with the conventional peeling technique (n = 5) or the inverted/free internal limiting membrane flap technique (n = 5) were included. In the peeling group, the percentage of white pixels ranged from 7.22% to 18.40% in the 0.5 × 0.5-millimeter area in the macular center; the mean postoperative logarithm of the minimum angle of resolution best-corrected visual acuity was 0.3 ± 0.2. In the inverted flap group, the percentage of white pixels ranged from 3.65% to 8.93% in the 0.5 × 0.5-millimeter area in the macular center; the mean logarithm of the minimum angle of resolution best-corrected visual acuity was 0.9 ± 0.4. Conclusions: A simple method of optical coherence tomography angiography imaging analysis of the outer retina using a binarization technique of the black and white pixels was created and may have functional implications during the analysis of the healing process after macular hole surgery. We hypothesized that higher numbers of white pixels correspond to viable cellularity and better prognoses postoperatively. [ABSTRACT FROM AUTHOR]

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Purposes: To compare surgeons' opinions regarding idiopathic full-thickness macular hole (MH) surgery by using traditional microscopy and three-dimensional (3-D) visualization system. To analyze the required time for pars plana vitrectomy (PPV) and for internal limiting membrane (ILM) rhexis by using both visualization methods. To evaluate anatomical surgical results. Methods: Four surgeons (surgeon 1, fellows 1, 2, 3) performed the total of 40 surgeries for treating MHs. Each one performed 10 surgeries (5 with traditional microscopy and 5 with 3-D visualization). The completion time for PPV and ILM rhexis was determined by using both methods. Ergonomics, educational value, image sharpness, depth perception, field of view and technical skills were analyzed through answering a questionnaire. Results: Forty patients were included in the study. The MH size for surgeon 1, fellows 1, 2 and 3 groups, individually, ranged from 237 to 602 μm; 228 to 590 μm, 271 to 611 μm and 289 to 600 μm, respectively. In the 3-D and in the traditional microscopy subgroups (which includes all 4 physicians on the use of one or the other method), the MH size ranged from 228 to 602 μm and 237 to 611 μm, respectively. Comparisons between the average time for full PPV and ILM rhexis by using the two methods were non-significant, neither in each individual case of 3-D surgery for each surgeon. Surgeon 1 had always been faster than his fellows. Depth perception was rated as similar for both methods. Field of view and educational values were rated as superior when using the 3-D system. Image resolution and ergonomics were rated as superior when using traditional microscopy. Technical skills strongly tended toward 'superiority' when using traditional microscopy. Thirty-six (90%) full-thickness MHs were successfully closed with one surgery. Conclusion: The 3-D system for MH surgery had a short learning curve and was a refined educational tool, when used with reduced illumination and precise focus. Concerning MH surgery, heads-up method was similar to traditional microscopy regarding length of time and anatomical surgical results. Heads-up surgery may become a new pattern for ophthalmic surgery as ongoing improvements are applied. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate diathermy to minimize sclerotomy leakage during small-gauge vitrectomy and prevent ocular hypotony. Methods: This observational prospective study included 327 patients (327 eyes) who underwent diathermy to close the sclerotomy sites during 23-gauge pars plana vitrectomy (PPV). All patients were operated by a single surgeon (ED) and evaluated at 30 and 60 days postoperatively. Patients with glaucoma, topical/systemic steroids use exceeding 30 days, ocular inflammation, or trauma were excluded. Chi-square, Kruskal–Wallis, Fisher Exact test, and multivariate statistical analyses were performed to evaluate potential risk factors. The primary outcomes were open sclerotomies, leakage, and ocular hypotony. Results: Sclerotomies remained open in 12 (3.6%) and 2 (0.6%) patients, respectively, at 30 and 60 days postoperatively, revealing no case of ocular hypotony. Leakage only occurred in four patients (1.2%) during week 1 postoperatively. Multivariate analysis indicated that additional vitreoretinal surgeries and longer surgeries were risk factors for persistent sclerotomy opening. Conclusion: Diathermy was safe and feasible to close sclerotomies. Vitreoretinal surgery reoperations and longer surgeries were the most significant (P<0.05) risk factors for persistent sclerotomy opening, which may be functionally closed without evidence of leakage or ocular hypotony. [ABSTRACT FROM AUTHOR]

Pars plana vitrectomy is a challenging, minimally invasive microsurgical procedure due to its intrinsic manoeuvres and physiological limits that constrain human capability. An important human limitation is physiological hand tremor, which can significantly increase the risk of iatrogenic retinal damage resulting from unintentional manoeuvres that affect anatomical and functional surgical outcomes. The limitations imposed by normal physiological tremor are more evident and challenging during 'micron-scale' manoeuvres such as epiretinal membrane and internal limiting membrane peeling, and delicate procedures requiring coordinated bimanual surgery such as tractional retinal detachment repair. Therefore, over the previous three decades, attention has turned to robot-assisted surgical devices to overcome these challenges. Several systems have been developed to improve microsurgical accuracy by cancelling hand tremor and facilitating faster, safer and more effective microsurgeries. By markedly reducing tremor, microsurgical precision is improved to a level beyond present human capabilities. In conclusion, robotics offers potential advantages over free-hand microsurgery as it is currently performed during ophthalmic surgery and opens the door to a new class of revolutionary microsurgical modalities. The skills transfer that is beyond human capabilities to robotic technology is a logical next step in microsurgical evolution. [ABSTRACT FROM AUTHOR]

Objective: To compare two different laser strategies of panretinal photocoagulation for diabetic retinopathy. Methods: Single-center, randomized study including 41 eyes treated with 577-nm multispot laser with a 20-ms pulse duration (group 1) or a 532-nm single-spot laser with a 100-ms pulse duration (group 2). The outcomes included best-corrected visual acuity (BCVA) and imaging changes at baseline, 6 and 12 months, laser parameters, and results of subjective pain analysis. Results: At 12 months, the treatments did not differ significantly in BCVA, central retinal thicknesses (CRTs), improved macular edema, vitreomacular interface changes, patient-reported pain scores, or angiographic responses. Group 1 had significantly fewer treatment sessions but used more laser spots (p < 0.001). Conclusion: The multispot laser required fewer applications with more spots delivered to compensate for lower fluency, showing similar patient tolerance to single-spot laser. Both groups maintained the initial visual acuities and CRTs; about 50% of cases had vitreomacular interface changes and improved macular edema, with similar angiographic improvements after 12 months. [ABSTRACT FROM AUTHOR]

Purpose: To test the applicability of the acai dye at a 25% concentration for identifying the posterior hyaloids and internal limiting membranes (ILMs) during pars plana vitrectomy (PPV) in human eyes with macular holes (MHs).Methods: This study included 25 patients with chronic idiopathic MHs. The exclusion criteria included glaucoma, previous significant ocular conditions, and previous ocular surgeries except uncomplicated cataract. Ten surgeons performed 23-gauge four-port PPV, phacoemulsification, posterior hyaloid detachment, ILM peeling guided by dye staining, and perfluoropropane injection. The patients remained prone for 5 days postoperatively. The patients were evaluated postoperatively after 1, 30, and 180 days. The surgeons completed a questionnaire regarding the dye's staining abilities.Results: The posterior hyaloids and ILMs stained purple in all eyes. The final best-corrected visual acuity improved significantly (p < 0.001) from preoperatively (1.37 ± 0.29) to 180 days postoperatively (1.05 ± 0.43). The MHs closed in 76% of eyes.Conclusion: The acai dye at a 25% concentration identified posterior hyaloids and ILMs during PPVs in humans. Dye toxicity was unlikely. [ABSTRACT FROM AUTHOR]

Introduction: There are few real-life studies on the intravitreal 0.7-mg dexamethasone implant for the treatment of diabetic macular edema (DME) conducted in Latin America. We aimed to assess the effectiveness and safety of this implant in clinical practice. Methods: Twenty-seven centers from Brazil and one from Argentina provided information on patients with DME treated with Ozurdex. The efficacy outcome variables were best-corrected visual acuity (BCVA) in Snellen and central retinal thickness (CRT). Safety was assessed by the elevation in intraocular pressure (IOP), occurrence of cataracts, and adverse events. Results: A total of 329 eyes (both treated cases and naïve eyes) from 282 patients underwent treatment. The time since diagnosis of DME ranged from 1 to 156 months. The median BCVA was 0.7 logMAR/50 letters at baseline and 0.3 logMAR/70 letters after treatment (both p < 0.001). Median CRT values decreased from 425 µm at baseline to 270 µm after treatment (p < 0.001). Increases in IOP of at least 10 mm Hg were observed in 7.4% of eyes, and 4% of eyes had cataract evolution. No cases of endophthalmitis were reported. Conclusion: These real-life results suggest that the intravitreal dexamethasone implant is effective and safe for eyes with DME. [ABSTRACT FROM AUTHOR]

Purpose. To classify and quantify anthocyanins in a vital dye extracted from the acai fruit (Euterpe oleracea), adjust pH and osmolarity, and perform lyophilization to develop a new chromovitrectomy dye. Methods. Three dye concentrations 10%, 25%, and 35% (equivalent to 100, 250, and 350mg of lyophilized acai fruit pulp extract samples) were evaluated when diluted in 1 ml of phosphatebuffered solution (pH 7 and 300 mOsm). The dye was analyzed by mass spectrometry and high-performance liquid chromatography (HPLC) to identify and quantify anthocyanins molecules. Results. The pH and osmolarity correction and lyophilization were performed without damaging the anthocyanin molecular structure. Mass spectrometry confirmed the presence of five anthocyanins in the three concentrations of the dye. Cyanidin-3-O-glucoside was the major anthocyanin found. HPLC showed that the concentration of anthocyanin was similar, independent of the dye concentration tested. Conclusions. Lyophilization and the correction of pH and osmolarity (7.00 and 300 mOsm, resp.) were performed successfully. Five anthocyanins are present in the dye from the acai fruit. The major anthocyanin is cyanidin-3-O-glucoside. Independent of the dye concentration tested, the anthocyanin concentration was similar. Standardized chemical characteristics of this new dye may allow its use during chromovitrectomy in humans. [ABSTRACT FROM AUTHOR]

Purpose To report the long-term anatomical and visual outcomes of intravitreal bevacizumab (IVB) monotherapy in naive choroidal neovascularisation (CNV) caused by myopia. Methods Retrospective analysis of naive CNV secondary to myopia that underwent antivascular endothelial growth factor monotherapy was performed. Collected data included demographic details, clinical examination details including visual acuity at presentation and follow-up with imaging and treatment details. Main outcome measures were resolution of CNV activity at the last visit. Secondary outcomes included change in visual acuity, number of injections and adverse events. results Thirty-three eyes of 31 subjects with a mean age of 51.48±16.4 years were included. The mean follow-up was 66.47 months. 27 eyes had type 2 CNV and the rest seven eyes had type 1 CNV. The mean number of IVB injections per eye was 4.9. Mean visual acuity at baseline reduced from 0.65±0.33 logMAR units (Snellen equivalent=20/89) to 0.73±0.50 logMAR units (20/107) at final follow-up (p=0.003). The mean central macular thickness decreased from 309.31±86 µm at baseline to 267.5±70.89 µm at the last visit (p=0.03). However, visual acuity was maintained (±1 line of baseline) in 13 eyes (39.4%), ≥2 line improvement in nine (27.3%) eyes and more than two lines worsening in 11 eyes (33.3%). Foveal atrophy was observed at baseline and last visit in 6 (12.5%) and 14 (29.1%), respectively (p=0.007). No systemic adverse events were observed. Conclusion IVB monotherapy is safe and effective for long-term treatment of CNV secondary to myopia in real life. [ABSTRACT FROM AUTHOR]

Background and Objectives: MHAA4549A, a human anti-influenza immunoglobulin (Ig) G1 monoclonal antibody, is being developed to treat patients hospitalized for influenza A infection. This study examined the pharmacokinetics (PKs) of MHAA4549A in a phase IIa, randomized, double-blind, dose-ranging trial in healthy volunteers challenged with influenza A virus.Methods: Serum PK data were collected from 60 subjects in three single-dose groups (400, 1200, or 3600 mg) who received MHAA4549A intravenously 24-36 h after inoculation with the influenza A virus. Nasopharyngeal swab MHAA4549A concentration data were collected on days 1-8, and all subjects, including the placebo group, received 75 mg oseltamivir twice daily from days 7 to 11. Plasma samples were collected 4 h postdose on day 8 for oseltamivir and its active metabolite oseltamivir carboxylate (OC) (all subjects, n = 100), including subjects treated with oseltamivir alone and placebo. Noncompartmental analysis was performed for both nasal and serum PKs.Results: MHAA4549A showed dose-proportional serum PKs with a long terminal half-life (approximately 21.9-24.6 days) and slow clearance (approximately 152-240 mL/day); however, nasopharyngeal swab PKs were not dose proportional. No differences in mean plasma concentrations of oseltamivir and OC at 4 h postdose on day 8 were observed between the MHAA4549A treatment and placebo groups. No subjects who received MHAA4549A developed anti-drug antibodies.Conclusion: MHAA4549A serum PKs were consistent with that of a human IgG1antibody without known endogenous targets. MHAA4549A showed nonlinear PKs in nasopharyngeal swab samples, which will guide future dose selection to achieve the high drug concentrations needed at the site of action for efficacy. These data demonstrate no PK interactions between MHAA4549A and oseltamivir, and support flat dosing.Trial Registration: ClinicalTrials.gov identifier, NCT01980966. [ABSTRACT FROM AUTHOR]

Sensitive and specific methodology is required for the detection and characterization of anti-drug antibodies (ADAs). High-quality ADA data enables the evaluation of potential impact of ADAs on the drug pharmacokinetic profile, patient safety, and efficacious response to the drug. Immunogenicity assessments are typically initiated at early stages in preclinical studies and continue throughout the drug development program. One of the potential bioanalytical challenges encountered with ADA testing is the need to identify and mitigate the interference mediated by the presence of soluble drug target. A drug target, when present at sufficiently high circulating concentrations, can potentially interfere with the performance of ADA and neutralizing antibody (NAb) assays, leading to either false-positive or, in some cases, false-negative ADA and NAb assay results. This publication describes various mechanisms of assay interference by soluble drug target, as well as strategies to recognize and mitigate such target interference. Pertinent examples are presented to illustrate the impact of target interference on ADA and NAb assays as well as several mitigation strategies, including the use of anti-target antibodies, soluble versions of the receptors, target-binding proteins, lectins, and solid-phase removal of targets. Furthermore, recommendations for detection and mitigation of such interference in different formats of ADA and NAb assays are provided. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate toxicity of acai fruit (Euterpe oleracea) dye concentrations in a rabbit model. Methods: Rabbits were injected intravitreously with 10%, 25%, and 35% acai dye concentrations. Control eyes received balanced salt solution (BSS). Electroretinogram (ERG), fundus imaging, fluorescein angiography (FA), optical coherence tomography (OCT), and light and transmission electron microscopy (LM/TEM) were performed. Results: Fundus imaging showed increased vitreous opacity with increased dye concentrations. FA and OCT showed normality with all concentrations. Comparisons between BSS and dye concentrations were analyzed using Kruskal–Wallis and Mood’s median test (p< 0.05). At 24 h, ERGs showed reduced amplitudes from baseline in all eyes. Median b-wave amplitudes nonsignificantly decreased and latency increased with 10% and 25%; findings were significant (p< 0.05) for 35%. LM and TEM showed no abnormalities for 10% and 25%. With 35%, TEM showed ganglion cell edema at 24 h that resolved after 7 days. Vacuolization, multilamellar bodies, and nerve bundle damage occurred at 24 h/7 days in the inner nuclear layer. Mitochondrial cristae disruption occurred in the inner photoreceptor segment at 24 h that decreased by 7 days. Conclusion: Ten and twenty-five percent concentrations were safe and may improve identification of the posterior hyaloid and internal limiting membrane during chromovitrectomy in humans. [ABSTRACT FROM PUBLISHER]

Background/aims To report the long-term anatomical and functional outcomes of patients with centre-involved diabetic macular oedema (DME) treated with intravitreal bevacizumab (IVB). Methods Retrospective case series. Patients diagnosed with centre-involved DME that were treated with at least one injection of 1.25 mg IVB and had a minimum follow-up of 60 months. Patients underwent measurement of best-corrected visual acuity (BCVA), ophthalmoscopy, optical coherence tomography and fluorescein angiography at baseline, 6-month, 12-month, 24-month, 36-month, 48-month and 60-month visits. The paired samples t test was used to compare the central macular thickness (CMT) and BCVA with baseline values. Statistical significance was indicated by p<0.05. Results Two hundred and one consecutive patients (296 eyes) were included. The mean number of IVB injections per eye was 8.4±7.1 (range: 1–47 injections). At 5 years, the BCVA remained stable at 20/100 (logarithm of the minimum angle of resolution=0.7±0.4). Eighty-six (29%) eyes improved ≥2 lines of BCVA, 129 (43.6%) eyes remained stable and 81 (27.4%) eyes lost ≥2 lines of BCVA at 60 months. Mean CMT decreased from 403.5±142.2 μm at baseline to 313.7±117.7 μm over 5 years follow-up (p≤0.0001). Conclusions The early visual gains due to IVB were not maintained 5 years after treatment. [ABSTRACT FROM AUTHOR]