People for a long time had been treated during their pregnancy with DES and there have been known to be toxic and adverse effects to the hormone therapy. "Exposure to DES has been associated with an increased risk for breast cancer in DES mothers (relative risk, <2.0) and with a lifetime risk of clear-cell cervicovaginal cancer in DES daughters of 1/1000 to 1/10 000." Side effects of DES are proving to be long-term as it can cause increased risks to cancer after use. There will be continued work to see how far the adverse effects of DES will go after previous therapy as many women had used this during pregnancy and there is a long line to see how it will effect offspring and the mothers longer-term. Regulations
In 1938, the ability to test the safety of DES on animals was first obtained by the FDA. The results from the preliminary tests showed that DES harmed the reproductive systems of animals. The application of these results to humans could not be determined, so the FDA could not act in a regulatory manner.New Drug Applications for DES approval were withdrawn in 1940 in a decision made by the FDA based on scientific uncertainty. However, this decision resulted in significant political pressure, so the FDA came to a compromise. The compromise meant that DES would be available only by prescription and would have to have warnings about its effects on the bottle, but the warning was dropped in 1945.
Diffuse lamellar keratitis (DLK) is a sterile inflammation of the cornea which may occur after refractive surgery, such as LASIK. Its incidence has been estimated to be 1 in 500 patients, though this may be as high as 32% in some cases. Signs and symptoms
Patients typically present within one week of surgery with eye pain, photophobia, conjunctivitis, or excessive tear production. Risk factors
DLK is predominantly associated with Lasik, as the creation of a flap creates a potential space for cells to accumulate. Individuals with atopic conditions with pre-existing allergic conjunctivitis, or ocular rosacea, are more prone to developing the condition after surgery. Some authors have reported that moderate to severe eye allergies and chronic allergic conjunctivitis are an absolute contraindication to the LASIK procedure. This is in distinction to findings of earlier studies. Keratitis can also occur after photorefractive keratectomy (PRK), although because it occurs in the setting of infection, it is distinct from the sterile infiltrates of DLK. DLK can also occur following myopic keratomileusis, in which a disc of corneal tissue is removed, shaped and sutured back into place, although this technique is more historical, having been replaced by Lasik and PRK. Pathology
DLK is usually seen after refractive surgery. Neutrophils infiltrate the corneal stroma in a diffuse, multifocal pattern. Infiltration is confined to the surgical flap interface with no posterior or anterior extension, and overlying epithelium most often remains intact. As it is a sterile process, cultures based on swab tests are negative.