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Isaac wears a contact lens on his left eye.
All fired tears will have a shield around them, allowing them to destroy enemy projectiles at the cost of destroying themselves.
- Fire Mind - Tears retain the flaming effect, but remove the chance of explosion.
- IPECAC - Shots explode upon contact any hostile projectile, making them harder to damage enemies while even increase the possibility of harming Isaac himself.
- Mysterious Liquid - Overrider, Mysterious Liquid has no effect.
- Chocolate Milk - It is not advised to charge shots as they can be destroyed by any little projectile. However, the player can spam the fire key in order to shoot in a rapid succession, making this combination more useful.
- Brimstone, Technology, Technology 2 and Mom's Knife - Beams, lasers and the knife can also destroy enemy projectiles as their damage 'ticks'.
- Piercing tears like Cupid's Arrow - Tears pierce through projectiles rather than being destroyed.
- Rubber Cement - Tears bounce off hostile projectiles rather than instantly being destroyed, allowing them to destroy other projectiles again or damage enemies.
- Polyphemus - Hostile projectiles are treated as enemies: Polyphemus tears will pass through them with reduced damage.
- The Ludovico Technique - The Ludovico tear can destroy projectiles without being destroyed, making it an effective shield when facing enemies that use bullets as their main attack like Isaac.