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The management of some ocular surface diseases may be enhanced by the overnight wear of a rigid gas-permeable (RGP) scleral contact lens (ScCL). There is little information of the hypoxic effect of extended RGP ScCL wear. The authors measured the corneal swelling after overnight wear of a rigid gas permeable scleral contact lens in normal subjects.Four subjects wore an RGP ScCL overnight in 1 eye only on 4 occasions. The following morning the lens was removed immediately before optical pachymetry, and the corneal thicknesses of both eyes were measured by a masked observer. On another four occasions optical pachymetry was performed, but the lens was not worn the previous night. For each subject the lens was of the same thickness. Specular microscopy was used to estimate endothelial cell density.There were no adverse effects, and subjects reported no difficulties in handling the lenses. Overnight wear of ScCL induced a variable amount of corneal swelling among subjects from 4.9% to 17.5%. The overnight swelling correlated strongly with endothelial cell density.Overnight wear of ScCL caused an increased degree of corneal swelling compared with daytime wear. This degree of swelling should not rule out overnight therapeutic ScCL wear if the disease process is deemed to be more damaging than the hypoxic effect of an RGP ScCL worn overnight. However, when used for refractive correction, they should not be left in overnight.