1. He lost his sight.
  2. He lost his eyesight.

Are both natural and are there any differences between them?

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No, not necessarily. Since the eye is our visual aide, an impairment to our eyes will lead to loss of eyesight or sight. But let us consider an example.

Pilot : Control, I've lost sight of the bogey in the storm clouds.

Now, this doesn't mean that the pilot has lost his eyesight. It just means that he cannot see what he was seeing, any longer. But that is the case of 'lost sight of'.

But when you say 'He lost his sight', it generally means that he cannot see. When you put it that way, it means the same. For the sentences you have mentioned, the meaning remains the same. However, 'losing sight' need not mean the same thing as 'losing eyesight'.

In general, 'Losing sight' can mean that the subject cannot see because of a problem or an obstruction, that need not be related to his eye, but affects his line of sight. 'Losing eyesight' means that the subject has been permanently or temporarily been blinded.

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