Recombinant human nerve growth factor (rhNGF) has shown promise as a treatment for dry eye disease in a phase I clinical trial.
“In this study, 4 weeks treatment with rhNGF eye drops at both 4 Î¼g/mL and 20 Î¼g/mL was effective in improving ocular surface damage and dry eye symptoms,” wrote Marta Sacchetti from the University of Sapienza of Rome in Rome, Italy and colleagues.
They published the finding in the British Journal of Ophthalmology.
The finding could lead to a much-needed new therapy for a disease that remains both common and difficult to treat, the researchers said.
Currently most treatments aim at either lubricating the exposed epithelia with tear substitutes or at controlling ocular surface inflammation with immunosuppressive drugs or steroids.
“Development of novel therapies targeting different pathogenic mechanisms is sought-after,” wrote the researchers.
Nerve growth factor (NGF), the first neurotrophin to be discovered, plays a key role in modulating the central and peripheral nervous, endocrine, immune and visual systems.
Preliminary clinical studies have shown that NGF drops from mice can safely and effectively treat neurotrophic keratitis and autoimmune corneal ulcers in humans. A novel recombinant human NGF produced in Escherichia coli (Cenergermin) received European Medicine Agency authorization in 2017 for these indications.
Other studies have suggested that NGF can improve ocular surface wound healing and sensitivity, and increase tear production and conjunctival goblet cell density.
To get a preliminary understanding of the safety and efficacy of rhNGF, Sacchetti and her colleagues enrolled divided 40 consecutive patients with moderate to severe non-Sjogren dry eye disease into 2 groups of 20. Both groups received rhNGF drops twice per day for 4 weeks.
One group received rhNGF in a concentration of 20 µg/mL. The other group received a concentration of 4 µg/mL. While both eyes were treated in all patients, results were only recorded for the more severe eye.
Both groups appeared to benefit from the treatment. On the Symptoms Assessment in Dry Eye (SANDE) scale, the high-dose group improved in frequency from 55.3 at baseline to 28.4 at 4 weeks and in severity from 52.7 to 25.9 over the same time period. The low-dose group improved in frequency from 59.7 to 33.5 and in severity from 60.1 to 31.5. These changes were all highly significant statistically.
Both groups also experienced improved ocular surface damage as measured by lissamine green (LG) staining score. Both groups also improved significantly on the Ocular Surface Disease Index (OSDI).
Tear film production improved significantly in the high-dose group as measured by the Schirmer test I: from a baseline of 4.2 mm/5 min to 9.4 mm/5 min. But the change in the Schirmer test I for the low-dose group, from 5.2 mm/5 min to 8.2 mm/5 min, was not statistically significant.
The results were similar for tear film breakup time (TFBUT) and tear osmolarity: the improvements were statistically significant in the high-dose group, but not in the low-dose group.
The benefits partially persisted when the researchers followed up 4 weeks after the treatment ended.
Altogether the patients experienced 101 adverse events. The researchers classified 78 of these as eye disorders, but only 15 as treatment-related, including abnormal sensation in the eye, eye pain eye irritation, eye pruritus, vision blurred eye discharge, eyelid pain and eyelid sensory disorder. Only one patient discontinued treatment due to an adverse event: a bacterial infection. The number of adverse events was similar in the 2 groups.
Citing previous studies, the researchers speculated that the treatment stimulated ocular surface epithelial healing. Its effect on tear film breakup time could result from an increase in human goblet cell density and production of Mucin-5AC, which regulates tear film stability.
The increased tear production could result from an increased ocular surface sensitivity and tear reflex, they wrote.
However, they cautioned that a placebo effect cannot be ruled out, since patients were aware of the treatment they were receiving. The researchers called for randomised, controlled trials to validate these results in larger populations.