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Background and objectiveTo develop a safe and efficient surgical procedure for subretinal implantation into porcine eyes of a human embryonic stem cell-derived retinal pigmented epithelium (hESC-RPE) monolayer seeded onto a Parylene-C scaffold. This implant is referred to as CPCB-RPE1.Materials and methodsUltrathin Parylene-C scaffolds were seeded with hESC-RPE and surgically implanted into the subretinal space of Yucatan mini pigs (n = 8). The surgery consisted of pars plana vitrectomy, induction of a limited retinal detachment, and peripheral retinotomy for insertion of the monolayer using a novel tissue injector, followed by silicone oil tamponade injection, laser photocoagulation around the retinotomy site, and inferior iridectomy. Oral cyclosporine was administered from day 1 and during the entire follow-up period. Three months later, the animals were euthanized and the eyes and major organs were submitted for histological analysis. Adjacent sections underwent immunohistochemical analysis to detect human cells using anti-TRA-1-85 (human blood group antigen) antibody and DAPI antibodies.ResultsThe cell monolayer was immunopositive for TRA-1-85 3 months after implantation and migration from the Parylene-C scaffold was not detected. One eye had a mild inflammatory reaction around the implant that was negative for human biomarkers. No intraocular or systemic tumors were detected.ConclusionThe hESC-RPE cells survived for 3 months in this animal model. The surgical procedure for subretinal implantation of CPCB-RPE1 is feasible and safe, without cell migration off the scaffold or development of ocular or systemic tumors.

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]

A study of 140 first- and second-grade classrooms and 1,925 students in the Brazilian states of Bahia and Ceara examined teaching practices and teacher behaviors in the classroom and their effects on students' early literacy achievement, as well as the influences of student, home, teacher, and school characteristics on literacy scores. (SV)

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]

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