Double blind, randomised, placebo controlled, crossover, multicentre study to determine the eYcacy of a 0.1% (w/v) sodium hyaluronate solution (Fermavisc) in the treatment of dry eye syndrome

Background/aims—Hyaluronan (sodium hyaluronate) has been shown to confer objective and subjective improvement in patients with dry eye syndrome. This study compared the eYcacy and safety of a 0.1% solution of hyaluronan with 0.9% saline, when administered topically to the eye, in the treatment of symptoms of severe dry eye syndrome. Methods—A randomised, double blind, crossover clinical trial in which subjects were randomised to receive either hyaluronan or saline, applied as one or two drops to the eye, three or four times a day or as required. After 28 days’ treatment, subjects crossed over to the other study medication for a further 28 days’ treatment. Results—70 subjects were included in the analyses of eYcacy and significant improvements in Schirmer’s score (p=0.0006) and rose bengal staining score (p=0.0001) were observed during treatment with hyaluronan. In a subjective assessment of the eVectiveness of two treatments, a majority of subjects felt that hyaluronan was more eVective than saline in alleviating the symptoms of burning and grittiness (p<0.001). No adverse events attributable to hyaluronan treatment were reported. Conclusion—The study demonstrates a clear benefit of hyaluronan over saline, in both subjective and objective assessments of dry eye syndrome. Hyaluronan was shown to be well tolerated. (Br J Ophthalmol 1999;83:1121–1124) Hyaluronan, a polymer of N-acetylglucosamine and glucuronic acid, is widely distributed in the skin, connective tissue, and synovial fluid. In the eye, hyaluronan is found in the vitreous, the aqueous humour, and in the connective tissues of the drainage angle. Dry eye results from a diminished supply of tears to the eye when age related atrophy reduces the formation of tears. Some destructive processes also aVect the lacrimal gland and cause dry eye. In keratoconjunctivitis sicca (KCS), lacrimal gland secretion is decreased, the precorneal tear film is hypertonic, and the tears have a decreased lysozyme content. Sjögren’s syndrome is a chronic autoimmune disease characterised by lymphoid cell infiltration of the lacrimal and salivary glands. This lymphocyte influx is paralled by acinar and ductal cell destruction leading to diminished glandular secretions. In primary Sjögren’s syndrome there is no associated connective tissue disease while in secondary disease, patients exhibit connective tissue disorders such as rheumatoid arthritis and systemic lupus erythematosus. A topical application of sodium hyaluronate has been shown to confer both subjective and objective improvement in patients with dry eye syndrome arising from Sjögren’s syndrome or KCS. Hyaluronan has also been reported to protect the corneal epithelium. The aim of the current study was to compare the eYcacy and tolerability of a 0.1% (w/v) solution of high molecular weight (2.5 million Da) hyaluronan, as sodium hyaluronate (Fermavisc, Fermentech Medical Ltd, Edinburgh), manufactured from a bacterial source by a process of continuous fermentation, with a physiological saline solution, in patients with dry eye syndrome of known aetiology. Patients and methods OBJECTIVE CLINICAL ASSESSMENTS Natural tear production was assessed by the Schirmer’s test, in which the extent of tear flow down a piece of filter paper inserted into the lateral part of the inferior fornix of the eye is measured over a 5 minute period. The use of local anaesthesia during the conduct of the test was recorded. The rose bengal test is used to locate degenerated corneal epithelial cells. The staining of the medial bulbar conjunctiva, lateral bulbar conjunctiva, and the cornea was visualised using a slit lamp microscope and the intensity of staining scored to a maximum of three points (maximum possible total score of 9). A higher intensity of staining indicates increased cell degeneration.