November 2018


Managing neurotrophic keratitis

by Chiles Aedam R. Samaniego EyeWorld Asia-Pacific Senior Staff Writer

Patient with neurotrophic keratitis from impaired trigeminal nerve function after surgery for meningioma. Extended wear of a high Dk silicone hydrogel soft lens, pictured here, resulted in healing of epithelial defect and clearing of corneal haze.
Source: Deborah Jacobs, MD


Addressing this orphan disease helps improve the ocular surface before surgery

Although neurotrophic keratitis (NK) is designated an orphan disease, with an estimated prevalence of less than 5 in every 10,000 individuals,1 the degenerative condition can lead to reduced corneal sensitivity, spontaneous epithelium breakdown, and impaired corneal healing.
A history of a number of ocular and systemic conditions raise the likelihood of neurotrophic keratopathy, most commonly herpes zoster, herpes simplex, neurosurgery with trigeminal damage or ablation, diabetes, chronic dry eye, and scleral buckle surgery for retinal detachment, said Stephen Pflugfelder, MD, James and Margaret Elkins Chair and director, Ocular Surface Center, Baylor College of Medicine, Houston.
Tumors and surgery for tumors such as acoustic neuromas, schwannoma, and meningiomas, medicamentosa with topical NSAID, certain glaucoma drops, and preservatives are also “common culprits,” according to Deborah Jacobs, MD, cornea and refractive surgery service, Massachusetts Eye & Ear, Boston, and associate professor of ophthalmology, Harvard Medical School.
Renal failure and immune suppression or compromise are some other systemic conditions that can cause NK, she said. Less commonly NK may be caused by congenital or genetic conditions associated with reduced corneal sensation—among them familial dysautonomia, Goldenhar syndrome, and Moebius syndrome.
Regarding the management of NK, Dr. Pflugfelder said that, unfortunately, “high-quality evidence doesn’t exist for most current therapies, and treatment strategies are based on case series and expert opinion”—only to be expected given the rarity of the condition.

First-line management

Dr. Jacobs initiates management with lubricants. “I think initial treatment is lubricant ointment QID,” she said. “Besides ointment QID it is important to reduce and modify topical regimens to reduce medicamentosa. Then I will go to bandage soft contact lenses [BSCL] or temporary tarsorrhaphy with transition to a scleral lens or PROSE [prosthetic replacement of the ocular surface ecosystem, BostonSight, Needham, Massachusetts] or permanent tarsorrhaphy depending on the clinical situation. Serum tears may be helpful for its lubricant and biological effects.”
Patching, she said, rarely works.
For Dr. Pflugfelder, hydrogel contact lenses are “the first line of therapy for NK. The trend is to use higher oxygen permeable silicone hydrogel lenses on an extended basis under frequent observation,” he said. “There are many of these lenses on the market.”
“I recommend using a high Dk (oxygen transmission) lens that is approved for therapeutic indications,” Dr. Jacobs said. “There are several on the market, including Air Optix Night & Day [Alcon, Fort Worth, Texas], AcuVue Oasys [Johnson & Johnson Vision, Santa Ana, California], and PureVision [Bausch + Lomb, Bridgewater, New Jersey]. I do not recommend using any daily disposable lens. I think it is important to observe the lens in the clinic after an interval of 30–60 minutes to check on retention and to make sure the lens is not too loose or too tight after it has settled. There is no set rule on how often the lens should be checked or exchanged for a new one. I typically would see a patient at 1 week and go from there. If there are lots of deposits, I would swap for a fresh lens. Otherwise, I might go as long as 2–4 weeks, sometimes longer, without changing or disinfecting the lens.”
Meanwhile, patients with herpes zoster ophthalmicus and NK may be treated with judicious use of topical steroids when there is concurrent intraocular and/or corneal stromal inflammation, Dr. Pflugfelder said.
Dr. Jacobs will also use a steroid. “After all, the surface breakdown may be related to edema from reduced endothelial function and it won’t get better unless the intraocular inflammation is controlled,” she explained. “Many neurotrophic patients require a topical, low-dose, ‘soft’ steroid to suppress the intrinsic corneal inflammation related to ocular surface breakdown. Typically, I use fluorometholone or loteprednol once or twice daily. I often choose ointment form at bedtime, which besides providing the dose of steroid has a depot effect because of longer dwell time and provides barrier lubrication that is far more effective than drops or gels.”
Dr. Jacobs emphasized the distinction between ointments and drops or gels. “Gels are not equivalent to ointment in this regard, as they are water-based and although they may have longer dwell time, they do not serve as a barrier against evaporation nor do they have the same protective effect against friction from the lids.”

Scleral lenses

“Scleral lenses and PROSE treatment can be used as therapeutic lens in NK,” Dr. Jacobs said. She explained that scleral lenses can be used for support of the surface and protection from the environment. “The disadvantage is that they are approved and are generally worn on a daily basis only and must be taken out and disinfected overnight. The advantage is that there is lower risk of infection than with overnight wear of a soft lens.
“There are some instances in which the mechanical contact of a soft lens is enough to trigger a breakdown,” she added. “Some patients with NK experience less breakdown in daily wear of a scleral lens or PROSE device than extended wear of a bandage soft contact lens.”
In Dr. Pflugfelder’s experience, scleral lenses do work better than soft contacts. “They can be used on an extended basis for 24–48 hours, if no corneal edema develops,” he said.

Amniotic membrane transplantation (AMT)

“I think that most NK corneas reepithelialize in a couple weeks if a good environment is offered,” Dr. Jacobs said. To that end, amniotic membrane transplantation offers only limited assistance. “AMT may downregulate intrinsic inflammation, but it is not as good as a BSCL or scleral lenses for improving the environment.”
Dr. Pflugfelder is more optimistic about AMTs. “There are reports of AMT healing NK,” he said. “I tend to use double-layer AMT fixated with fibrin tissue glue and covered with bandage contact lens and temporary tarsorrhaphy to enhance retention.”


“Tarsorrhaphy is an excellent option for patients who cannot or will not manage the regimens of frequent application of topical agents or application and removal of therapeutic lenses,” Dr. Jacobs said. “I bring it up immediately if there is already significant ulceration putting integrity of the globe at risk or if it is clear that adherence to regimens is going to be a problem because of medical, cognitive, or logistical challenges.”
While not in disagreement, Dr. Pflugfelder spoke more circumspectly regarding the procedure. “Permanent tarsorrhaphy is considered the last resort for this condition because it reduces vision/visual field and patients don’t like the appearance of the eye.”
However, Dr. Jacobs noted that “a 40% tarsorrhaphy is much less disfiguring than expected and can be very helpful in support of the surface.”

Down the pipeline

In terms of future options, “[b]iologics for support of the surface and regeneration of nerves hold promise,” Dr. Jacobs said. “I doubt any one of them will be a panacea for all NK. Some target nerve regeneration direction, others work by supporting the epithelium. What works for damage from multiple surgeries may not work for damage from VZV. Congenital or genetic problems may respond very specifically or not at all and may depend on the age of the patient at the time treatment is initiated.”
Dr. Pflugfelder has had experience with one of the drugs coming down the pipeline: cenegermin, a recombinant form of human nerve growth factor that was approved in the European Union for the treatment of NK in adults in July 2017.
“I was an investigator in the FDA Phase 3 clinical trial used for orphan drug approval,” he said. “Consequently, I don’t know whether patients received placebo or active. The clinical trial results are impressive with a significant difference in healing vs. vehicle (up to 75% healing in some studies) and lack of recurrence for an extended period after stopping the drug.”
Dr. Pflugfelder is not sure there is evidence that other therapies such as thymosin beta-4 factor and synthetic neurotrophin mimetics will be effective; however, regarding cenegermin, “I plan to use it when it becomes commercially available at the end of this year or early next year,” he said.


1. Sacchetti M, Lambiase A. Diagnosis and management of neurotrophic keratitis. Clin Ophthalmol. 2014;8:571–9.

Editors’ note: Dr. Jacobs was a full-time employee of BostonSight in the past 12 months, but has no financial interests in any contact lens or prosthetic device. Dr. Pflugfelder has no financial interests related to his comments.

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