Yubikey Manager is not needed to use ed25519-sk keys. They use only FIDO U2F functionality, so cheaper USB keys ($29 for a Yubico Security Key USB-C NFC vs $55 for the full Yubikey 5C NFC).
They are thus not limited to Yubico's proprietary functionality controlled by Manager, which has a wider attack surface than I am comfortable with, and are not limited to platforms running the Yubikey Manager software (e.g. on OpenBSD). Since the key has never been outside the USB enclave, there is no way it could have been surreptitiously copied, e.g. if there was a rootkit on the machine where the key was generated before copying to the Yubikey.
They are thus not limited to Yubico's proprietary functionality controlled by Manager, which has a wider attack surface than I am comfortable with, and are not limited to platforms running the Yubikey Manager software (e.g. on OpenBSD). Since the key has never been outside the USB enclave, there is no way it could have been surreptitiously copied, e.g. if there was a rootkit on the machine where the key was generated before copying to the Yubikey.