Statins offer promise in ophthalmology

Statins may help treat ocular inflammation, and are generally safe, but clinicians should watch for rare, serious adverse events, researchers say.

These medications come in synthetic and non-synthetic forms with differing effects, write Kenneth G-J. Ooi from Save Sight Institute in Sydney, Australia, and colleagues. They published an overview of the use of statins in Survey of Ophthalmology.

Statins inhibit 3-Hydroxy-3-methyl-gutaryl coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme in the mevalonate pathway for the biosynthesis of intracellular cholesterol.

They are immunomodulatory and anti-inflammatory, decrease thrombogenicity, reduce endothelial dysfunction and attenuate vascular remodeling and their antiproliferative, antioxidant and neuroprotective properties.

Topical atorvastatin can improve the symptoms and signs in dry eye and blepharitis, apparently through its anti-inflammatory effects.

The authors demonstrated this in their own pilot study, they write. Ten patients received atorvastatin drops (50 μM) 8 times a day for 4 weeks while continuing with their existing dry eye treatment if they wished. The researchers documented an improvement in fluorescein staining in the treated eye by more than 1 point from baseline to completion of the trial at week 4, in 9 of 10 patients.

Other researchers have noted an association between ocular dryness and systemic statins. Ooi and colleagues speculate that statins may disrupt cholesterol synthesis for meibum lipid homeostasis, or that the hypercholesterolemia for which the statins are prescribed may themselves cause dryness.

Statins may improve uveitis through their anti-inflammatory effect. While animal studies have had mixed results in models of uveitis, several clinical trials have shown benefits. In one retrospective, case-control study, patients who used statins were 48% less likely to develop uveitis than patients who didn’t. And a pilot trial showed that uveitis patients given statins required fewer steroid drops. Ooi and colleagues caution against using statins with cyclosporine, however.

Statins may also inhibit fibrosis in corneal wound healing. Though an assay did not find a statistically significant effect for lovastatin, the researchers write, this could be due to the variability of the effect.

Graves disease, one of the most common autoimmune diseases, often presents as thyroid-associated ophthalmopathy. In a study of risk factors, statin use was associated with a 40% decreased hazard for development of thyroid-associated ophthalmopathy. The authors note reports that statins given with intravenous glucocorticoids may produce liver dysfunction in these patients. But they point out that an analysis of 1,076 patients with thyroid-associated ophthalmopathy did not show an increased risk of liver disease.

Oral simvastatin has been associated with orbital myositis, a non-infectious inflammatory process primarily involving extraocular muscles. The authors speculate that oral simvastatin might inhibit coenzyme Q10, a key component in mitochondrial bioenergy transfer. They cite a study suggesting that the intensity of statin adverse events may be reduced with coadministration of CoQ10.

The drugs are being studied for their effects in multiple other ocular conditions, with preliminary results. Among the areas of ongoing research:
• Several studies have shown an association between statin usage and reduced risk of open-angle glaucoma.
• Research on the relationship of statins to cataracts has produced contradictory results, with some studies showing that statins increase the risk of cataracts and some the opposite.
• Laboratory and animal studies suggest that statins might promote trabeculectomy bleb survival.
• Other such studies have suggested they could be effective in treating proliferative vitreoretinal diseases, such as proliferative diabetic retinopathy and proliferative vitreoretinopathy. And small clinical trials have shown efficacy in slowing the loss of visual acuity in diabetic retinopathy.
• Preliminary evidence has raised the possibility that statins could reduce the impetus for drusen formation in age-related macular degeneration.