OXERVATE: Uses, Dosage & Side Effects
The first recombinant human nerve growth factor (rhNGF) eye drop, approved for the targeted treatment of moderate and severe neurotrophic keratitis in adults.
OXERVATE (cenegermin) is a prescription-only ophthalmic solution and the first and only targeted pharmacological treatment for neurotrophic keratitis, a rare degenerative corneal disease. It contains recombinant human nerve growth factor (rhNGF), structurally identical to the natural protein produced in the body, which supports the health and regeneration of corneal nerves and epithelial cells. OXERVATE is indicated for adults with moderate (persistent epithelial defect) or severe (corneal ulcer) neurotrophic keratitis. A single eight-week course of six drops per day is usually sufficient to heal the cornea in most responding patients. OXERVATE was granted orphan drug designation and was approved by the European Medicines Agency in 2017 and the U.S. Food and Drug Administration in 2018.
Quick Facts: OXERVATE
Key Takeaways
- OXERVATE (cenegermin) is the first and only approved eye drop containing recombinant human nerve growth factor (rhNGF) for the treatment of moderate or severe neurotrophic keratitis in adults.
- Treatment is administered as one drop in the affected eye six times per day at approximately two-hour intervals, for an eight-week course; a second course may be considered if healing is incomplete.
- The drug must be stored frozen at -20°C, thawed weekly in the refrigerator, and each multidose vial is strictly single-day use to preserve the protein’s stability.
- The most common side effects are local and transient: eye pain, ocular hyperaemia (redness), increased tearing, eyelid inflammation, and foreign body sensation.
- OXERVATE is a biological, orphan-designated medicine; pivotal REPARO and NGF0214 trials demonstrated complete corneal healing in approximately 65–72% of treated patients after eight weeks compared with 29–43% on vehicle.
What Is OXERVATE and What Is It Used For?
OXERVATE is an innovative ophthalmic medication that contains the active substance cenegermin, a recombinant human nerve growth factor (rhNGF). Cenegermin is manufactured in Escherichia coli using recombinant DNA technology and is structurally identical to the nerve growth factor produced naturally in the human body, including in the lacrimal gland and ocular surface tissues. Nerve growth factor is a member of the neurotrophin family of proteins, which play essential roles in the development, maintenance, and regeneration of nerve cells throughout the body, and particularly in the cornea of the eye.
OXERVATE is authorised for the treatment of moderate or severe neurotrophic keratitis in adults. Neurotrophic keratitis (also called neurotrophic keratopathy) is a rare, degenerative disease of the cornea caused by impairment of trigeminal nerve function. The trigeminal nerve is the major sensory nerve supplying the surface of the eye. When its function is reduced or lost, the cornea loses its protective reflexes (such as blinking and tearing in response to touch), its epithelial cells lose the trophic signals they depend on, and healing of even minor surface injuries becomes severely impaired. Without adequate treatment, neurotrophic keratitis can progress from a chronic persistent epithelial defect to corneal ulceration, stromal melting, and ultimately perforation of the cornea with irreversible vision loss.
Traditionally, neurotrophic keratitis has been classified using the Mackie staging system into three progressively more severe stages:
- Stage 1 (mild): Characterised by epithelial irregularities such as superficial punctate keratopathy without a defect in the corneal epithelium.
- Stage 2 (moderate): Defined by a persistent epithelial defect (PED) that fails to heal despite standard conservative care such as preservative-free lubrication, bandage contact lenses, and treatment of any underlying ocular surface disease.
- Stage 3 (severe): Involves deeper stromal involvement with corneal ulceration, and may be accompanied by stromal melting or impending perforation.
OXERVATE is specifically indicated for patients with Stage 2 and Stage 3 disease. It is the first pharmacological therapy ever approved for neurotrophic keratitis and represents a significant paradigm shift: instead of simply protecting the ocular surface mechanically, it addresses the biological deficiency at the heart of the disease by restoring trophic support to the corneal nerves and epithelial cells.
Common underlying causes of neurotrophic keratitis include reactivation of herpes simplex or herpes zoster (shingles) affecting the eye, previous eye surgery (including refractive procedures such as LASIK, cataract surgery, and surgery for trigeminal neuralgia), diabetes mellitus, long-term use of preserved topical medications (particularly those containing benzalkonium chloride), chemical or thermal ocular burns, and any condition causing damage to the trigeminal nerve such as tumours, neurosurgery, or stroke. Patients with these risk factors who develop persistent corneal epithelial defects should be evaluated by a cornea specialist so that neurotrophic keratitis can be diagnosed and treated promptly.
OXERVATE is a biological medicinal product. Cenegermin binds with high affinity to the TrkA (tropomyosin receptor kinase A) receptor and with lower affinity to the p75NTR receptor. Activation of these receptors on corneal epithelial cells, keratocytes, and sensory nerve fibres supports cell survival, proliferation, and differentiation, and promotes reinnervation of the damaged cornea. This mechanism directly addresses the pathophysiology of neurotrophic keratitis rather than merely protecting the ocular surface.
In the pivotal phase II REPARO trial (EMA, Europe) and phase II NGF0214 trial (FDA, United States), OXERVATE demonstrated statistically significant and clinically meaningful superiority over vehicle eye drops. In REPARO, complete corneal healing at eight weeks was observed in approximately 72% of patients treated with cenegermin 20 µg/mL, compared with 43% in the vehicle group. In NGF0214, complete healing was observed in approximately 65% of treated patients, compared with 29% in the vehicle group. Importantly, most healed patients remained healed at 12 months of follow-up, indicating durable benefit from a single treatment course.
What Should You Know Before Using OXERVATE?
Contraindications
OXERVATE should not be used in specific situations. Before your ophthalmologist starts treatment, the following must be ruled out:
- Known hypersensitivity: Do not use OXERVATE if you have a known allergy to cenegermin or to any of the excipients (trehalose dihydrate, L-methionine, hydrochloric acid, sodium hydroxide, mannitol, disodium hydrogen phosphate anhydrous, sodium dihydrogen phosphate dihydrate, or water for injections). Signs of an allergic reaction can include severe itching, swelling of the eyelid, rash around the eye, or difficulty breathing.
- Active ocular infection: Any active infection of the eye (bacterial, viral, fungal, or parasitic) should be diagnosed and treated before initiating OXERVATE. Nerve growth factor can stimulate cellular proliferation and might theoretically worsen certain infections if they are untreated.
Warnings and Precautions
If you experience sudden increase in pain, intense redness, yellow or green discharge, a white spot on the cornea, sudden worsening of vision, or severe light sensitivity during treatment, stop using OXERVATE and contact your ophthalmologist immediately. These may indicate an infection that requires prompt diagnosis and targeted treatment.
Before starting and during treatment with OXERVATE, inform your ophthalmologist if any of the following situations apply:
- Corneal thinning or impending perforation: Patients with advanced stromal melting, descemetocele, or imminent corneal perforation should be carefully evaluated. While OXERVATE can promote healing, surgical intervention (such as amniotic membrane transplant, tectonic keratoplasty, or tarsorrhaphy) may be needed first to stabilise the eye.
- Concurrent use of preserved eye drops: Benzalkonium chloride and similar preservatives can contribute to ocular surface toxicity and may impair the epithelial healing that OXERVATE is intended to promote. Your ophthalmologist may switch concomitant topical medications to preservative-free formulations where possible.
- Topical corticosteroids or NSAIDs: These medications can delay corneal healing. Their use should be minimised or, if clinically necessary, carefully monitored during the OXERVATE course.
- Eye pain and ocular hyperaemia: These are the most common side effects of OXERVATE and are usually mild to moderate and transient. However, new or worsening pain, especially with other symptoms, should be evaluated promptly.
- History of ocular or intracranial tumours: Nerve growth factor is a biologically active protein. Although no causal link has been established and systemic exposure from eye drops is negligible, patients with a history of tumours such as uveal melanoma or intracranial neoplasms should discuss the risks and benefits with their physician.
- Bilateral disease: Each multidose vial is used for one eye only per day; if both eyes are affected, separate supplies are needed. Your ophthalmologist will advise on how to manage treatment of both eyes safely.
Your ophthalmologist will perform detailed slit-lamp examinations, corneal sensitivity testing, and photographic or imaging follow-up to track epithelial healing, corneal reinnervation, and any emerging complications during the eight-week course.
Other Eye Drops and Medications
Inform your ophthalmologist and pharmacist about every eye drop, ointment, gel, or medication you use, including herbal and over-the-counter products. If you need to use more than one eye medicine, leave at least 15 minutes between OXERVATE and any other eye drop. Always apply eye ointments or gels last, as they can prevent subsequent drops from being absorbed properly.
Pregnancy and Breastfeeding
There is limited experience with the use of OXERVATE in pregnant women. Animal studies have not shown direct or indirect harmful effects on pregnancy, embryonic or fetal development, parturition, or postnatal development at doses substantially greater than those used in humans. Because systemic exposure to cenegermin following topical ocular use is negligible, the risk to a developing fetus is considered low. Nevertheless, OXERVATE should only be used during pregnancy if the potential benefit clearly outweighs any theoretical risks, and the decision should be made together with the treating ophthalmologist and obstetrician.
It is not known whether cenegermin is excreted in human breast milk following topical ocular administration, but given the minimal systemic absorption and the local action of the eye drops, transfer into breast milk is expected to be negligible. A decision on whether to continue or discontinue breastfeeding during OXERVATE treatment should be made on an individual basis.
No human data are available regarding fertility effects from cenegermin, but animal studies have not shown any impairment of male or female fertility at clinically relevant exposures.
Driving and Operating Machinery
OXERVATE may cause transient blurred vision immediately after instillation, as with most eye drops. You should wait until your vision has cleared before driving, cycling, or using machines. Some patients also experience temporary eye pain or discomfort that could briefly interfere with concentration.
Important Information About Ingredients
Each mL of OXERVATE contains 2.3 mg of sodium and 70 mg of trehalose dihydrate as a stabiliser. Although the sodium content is low, patients on a strict sodium-restricted diet should be aware of all sources. The preparation is preservative-free, which is particularly important for ocular surface disease because preservatives (notably benzalkonium chloride) are known to be toxic to corneal epithelial cells.
How Does OXERVATE Interact with Other Drugs?
Because OXERVATE is applied topically to the eye and systemic absorption is very low, conventional pharmacokinetic drug–drug interactions (involving enzymes such as CYP450) are not expected. No formal interaction studies with systemic drugs have been performed, and none are considered necessary on the basis of the drug’s route of administration and pharmacology.
The most relevant interactions for everyday practice are therefore topical in nature: they concern how OXERVATE is combined with other eye drops, ointments, gels, or contact lens solutions. Incorrect timing of application can either dilute OXERVATE, wash it out, or allow other products to impair the delicate ocular surface healing that the drug is intended to promote.
Major Interactions
| Interacting Drug or Product | Effect | Clinical Significance |
|---|---|---|
| Preserved eye drops (containing benzalkonium chloride) | Increased ocular surface toxicity and impaired corneal epithelial healing | Switch to preservative-free alternatives where possible during the OXERVATE course |
| Topical corticosteroids (e.g., dexamethasone, prednisolone eye drops) | Delay corneal wound healing; increased risk of infection and stromal thinning | Use only when strictly necessary; taper or discontinue before or during OXERVATE if possible |
| Topical NSAIDs (e.g., ketorolac, diclofenac, bromfenac) | Reported to impair corneal epithelial healing and, rarely, cause corneal melting | Avoid during OXERVATE treatment unless explicitly prescribed by your ophthalmologist |
| Antiviral eye drops (e.g., ganciclovir, aciclovir) for active herpes keratitis | Essential to control viral replication before or alongside OXERVATE; risk of viral reactivation if untreated | Treat active infection first; continue prophylaxis as per ophthalmologist’s instructions |
Minor Interactions
| Interacting Product | Effect | Clinical Significance |
|---|---|---|
| Preservative-free artificial tears and lubricants | Frequently co-administered to support ocular surface moisture | Compatible; always leave at least 15 minutes between drops |
| Eye ointments and gels | May block absorption of subsequent drops | Apply OXERVATE first, then wait at least 15 minutes, then apply ointment or gel |
| Contact lens solutions and rewetting drops | Contact lens wear is generally discouraged during active neurotrophic keratitis | Remove lenses before each OXERVATE dose; reinsert only after 15 minutes if clinically permitted |
| Systemic medications (oral/IV) | No clinically significant interaction expected due to negligible systemic absorption of cenegermin | Continue chronic systemic medications as usual, but always disclose them to your ophthalmologist |
OXERVATE is typically the only drug with disease-modifying activity for neurotrophic keratitis, but patients often use a combination of adjunctive treatments such as preservative-free lubricants, autologous serum eye drops, bandage contact lenses, or punctal plugs. Your ophthalmologist will coordinate these to maximise healing while respecting the 15-minute timing rule and preservative avoidance principle.
What Is the Correct Dosage of OXERVATE?
OXERVATE must only be prescribed and its use supervised by an ophthalmologist or other healthcare professional qualified in the management of neurotrophic keratitis. The dosing schedule is fixed and straightforward, but correct technique and timing are essential for the medicine to work properly and remain stable. Your ophthalmologist or pharmacist will demonstrate the application technique the first time you use the drops and will provide written instructions and a dosing diary.
Adults
Standard Adult Regimen
Dose: One drop in the conjunctival sac (the space between the lower eyelid and the eyeball) of the affected eye.
Frequency: Six times per day at approximately two-hour intervals during waking hours.
Duration: Eight consecutive weeks.
A single eight-week course is designed to achieve complete corneal healing in the majority of responders. Your ophthalmologist will typically review progress with slit-lamp examinations at weeks 2, 4, 6, and 8, and will consider an additional course only if partial healing remains after the first course.
Children and Adolescents
OXERVATE was initially authorised for adults only. In the European Union and several other jurisdictions, subsequent label extensions or paediatric studies have supported use in children and adolescents aged two years and above with moderate or severe neurotrophic keratitis, following the same dosing regimen as in adults. Because regional approvals and clinical data continue to evolve, paediatric treatment must be supervised by a paediatric ophthalmologist or cornea specialist experienced in the condition. OXERVATE should not be used in children under two years of age.
Elderly Patients
No dose adjustment is required for older adults (aged 65 years and over). Clinical trials included patients across a broad age range, and no meaningful differences in safety or efficacy were observed in the elderly. However, older patients often have multiple concomitant ocular and systemic conditions that can affect corneal healing, and their ophthalmologist will take these into account when planning and monitoring treatment.
Renal and Hepatic Impairment
No dose adjustment is needed for patients with kidney or liver impairment. Cenegermin is applied topically and systemic absorption is negligible, so these organs play no meaningful role in eliminating the drug. Formal studies in patients with renal or hepatic impairment have therefore not been conducted and are not considered necessary.
Missed Dose
If you forget a dose, apply it as soon as you remember, provided the next scheduled dose is not imminent. If it is almost time for the next dose, skip the missed dose and continue with your regular schedule. Do not apply a double dose to make up for a missed one. Occasional missed doses are unlikely to have a major impact on overall treatment success, but maintaining the six-times-daily schedule as consistently as possible gives the best chance of healing.
Overdose
An overdose from topical administration of OXERVATE is unlikely to cause serious harm because the ocular surface cannot retain more than a small volume of eye drops, and excess solution simply drains through the lacrimal system. If you or someone else accidentally instils more drops than prescribed, rinse the eye with lukewarm clean water or preservative-free saline and contact your ophthalmologist or pharmacist for advice. Systemic toxicity from accidental ingestion of the eye drops is not expected, but a poison information centre can be contacted for reassurance.
How OXERVATE Is Given
OXERVATE is a clear, colourless solution supplied as a weekly treatment pack containing seven multidose vials, a vial adapter, and seven pipettes (one for each day). Each multidose vial is used for a single day and then discarded, even if some medicine remains. The system is designed to preserve the stability and sterility of the recombinant protein, which is particularly sensitive to light, temperature, and microbial contamination.
A typical six-times-daily schedule spaced by roughly two hours might look like this: 07:00, 09:00, 11:00, 13:00, 15:00, 17:00. The exact times can be adapted to your day; the key principles are regular spacing and consistent use over the full eight weeks. Many patients set phone alarms or reminders, use a dosing diary, or pair doses with routine activities (such as meals or commuting) to maintain adherence.
1) Wash your hands thoroughly with soap and water.
2) If you wear contact lenses, remove them.
3) Attach the adapter to the vial and the pipette to the adapter as shown in the package leaflet.
4) Tilt your head back and pull down the lower eyelid to form a small pocket.
5) Hold the pipette above the eye without touching the eye, eyelashes, or any other surface.
6) Gently squeeze to deliver one drop into the pocket.
7) Close your eye gently for a few minutes. Pressing softly on the inner corner of the eye can reduce drainage into the tear duct.
8) Wipe away any excess solution with a clean tissue.
9) Wait at least 15 minutes before using any other eye drop or reinserting a contact lens.
Although you will apply OXERVATE yourself at home, every course must be initiated and monitored by an ophthalmologist. Do not start, extend, or repeat treatment without medical advice. Regular follow-up examinations confirm that the cornea is healing and that no complications (such as infection, melt, or perforation) are developing.
What Are the Side Effects of OXERVATE?
Like all medicines, OXERVATE can cause side effects, although not everyone gets them. The overall tolerability profile is favourable: most adverse effects are local to the treated eye, mild to moderate in intensity, and resolve either during or shortly after the eight-week course. Severe or systemic effects are uncommon. Your ophthalmologist will review side effects at each follow-up visit and help you manage them.
Local Ocular Reactions
Because OXERVATE is applied directly to an already vulnerable ocular surface, some local discomfort is expected, particularly during the first days or weeks of treatment as the nerves and epithelium regenerate. Many patients describe a gradual improvement in comfort as healing progresses. If symptoms are severe, worsening, or accompanied by marked vision changes, contact your ophthalmologist promptly.
Very Common
May affect more than 1 in 10 people
- Eye pain
Common
May affect up to 1 in 10 people
- Eye inflammation (ocular hyperaemia, redness)
- Increased tear production (lacrimation)
- Eyelid inflammation (blepharitis)
- Foreign body sensation in the eye
- Eye irritation and stinging or burning on instillation
- Photophobia (sensitivity to light)
- Headache
- Eye allergy
- Abnormal sensation in the eye
Uncommon
May affect up to 1 in 100 people
- Corneal deposits
- Corneal ulcer progression or new corneal defect
- Iritis or anterior uveitis
- Eyelid margin crusting or discharge
- Conjunctival hyperaemia with chemosis (swelling of the conjunctiva)
- Dry eye exacerbation
- Blurred vision beyond the immediate post-dose period
Rare
May affect up to 1 in 1,000 people
- Hypersensitivity reactions (localised eyelid rash, swelling, severe itching)
- Corneal oedema
- Corneal neovascularisation
Not Known
Frequency cannot be estimated from available data
- Severe allergic reaction (anaphylaxis) – theoretical given the protein nature of the drug, but not reported in pivotal studies
- Reactivation of herpetic keratitis in predisposed patients
Managing Side Effects
Most mild ocular discomfort can be managed with preservative-free artificial tears, cool compresses, and avoidance of triggers such as air conditioning, smoke, or prolonged screen time. Eye pain on instillation often diminishes after the first few doses as the ocular surface adapts. If pain is severe, persistent beyond the first two weeks, or associated with redness, discharge, or vision loss, contact your ophthalmologist. In some cases, short courses of supportive treatment (for example, preservative-free lubrication or, rarely, low-dose topical anaesthesia for a single follow-up examination) may be used.
Seek urgent ophthalmological assessment if you experience any of the following: sudden severe eye pain, marked decrease in vision, a new white spot on the cornea, intense redness with profuse discharge, severe light sensitivity, swelling of the eyelid with difficulty opening the eye, or signs of a severe allergic reaction (facial swelling, breathing difficulty).
If you experience any side effects, including any not listed here, report them to your ophthalmologist or pharmacist. You can also submit spontaneous reports to your national pharmacovigilance authority (for example, the EMA EudraVigilance system in Europe, the FDA MedWatch programme in the United States, or the MHRA Yellow Card Scheme in the United Kingdom). Reporting helps ensure that the safety profile of OXERVATE continues to be monitored in real-world use.
How Should OXERVATE Be Stored?
OXERVATE is a biological product and cenegermin is a protein that is inherently unstable in solution. The storage requirements reflect this: freezing preserves long-term stability, refrigeration preserves weekly stability, and single-day use preserves sterility and biological activity. Following the storage instructions precisely is essential for the medicine to work properly.
- Long-term storage: Keep OXERVATE in the freezer at -20°C (allowed range usually -15°C to -25°C) in its original carton to protect from light. Do not exceed the expiry date printed on the carton and vial label.
- Starting a weekly supply: Once a week, remove one weekly treatment pack from the freezer and place it in the refrigerator (2–8°C) for about 30 minutes to thaw. Do not thaw at room temperature, in warm water, or in a microwave.
- In use (weekly): After thawing, the weekly pack must be kept in the refrigerator between doses and used within 14 days. Do not refreeze.
- In use (daily vial): Each multidose vial, once the pipette has been attached, may be kept at controlled room temperature (below 25°C) for up to 12 hours of in-use time. Discard the vial and pipette at the end of that day, even if any solution remains.
- Appearance check: The solution should be clear and colourless. Do not use if it is cloudy, discoloured, or contains visible particles.
- Keep out of reach of children: Store the carton in a place children cannot access. Although systemic toxicity from accidental exposure is unlikely, eye drops should never be handled by small children.
- Travel: If you need to transport OXERVATE, use a validated cold chain (insulated bag with ice packs) and resume freezer or refrigerator storage as soon as possible.
Do not dispose of any unused medicine or waste materials via wastewater or household refuse. Ask your pharmacist how to dispose of medicines you no longer use. These measures protect the environment from inappropriate release of biological products.
What Does OXERVATE Contain?
Active Substance
The active substance is cenegermin, a recombinant human nerve growth factor (rhNGF) produced in Escherichia coli using recombinant DNA technology. Cenegermin is a 120-amino-acid homodimeric protein that is identical in sequence to the endogenous human nerve growth factor (beta subunit). Each mL of solution contains 20 micrograms of cenegermin, and each single-day multidose vial delivers the number of drops required for a full day of therapy.
Inactive Ingredients (Excipients)
OXERVATE is preservative-free. The excipients are chosen to stabilise the protein in solution, maintain physiological pH and osmolality, and improve tolerability on the ocular surface:
- Trehalose dihydrate – stabiliser and tonicity agent
- Mannitol – tonicity agent
- L-methionine – antioxidant that protects the protein from oxidation
- Disodium hydrogen phosphate anhydrous – buffering agent
- Sodium dihydrogen phosphate dihydrate – buffering agent
- Hydrochloric acid and/or sodium hydroxide – for pH adjustment
- Water for injections – solvent
Appearance and Packaging
OXERVATE is a clear, colourless eye drop solution with a physiological pH and osmolality similar to natural tears. It is packaged in weekly cartons that each contain seven multidose vials (one per day), one vial adapter per vial, and seven disposable pipettes (one per day). The packaging is designed for a complete eight-week course, meaning a full prescription comprises eight weekly cartons.
Marketing Authorisation Holder and Manufacturer
OXERVATE is developed, manufactured, and marketed by Dompé farmaceutici S.p.A. (headquartered in Italy). The product was granted orphan medicinal product designation by the European Medicines Agency in December 2015 and received marketing authorisation from the European Commission in July 2017. The U.S. Food and Drug Administration approved OXERVATE in August 2018. Post-approval regulatory commitments include long-term safety monitoring and patient registries to follow real-world outcomes in this rare disease population.
Frequently Asked Questions About OXERVATE
OXERVATE (cenegermin) is used to treat moderate (persistent epithelial defect) or severe (corneal ulcer) neurotrophic keratitis in adults. Neurotrophic keratitis is a rare corneal disease caused by impaired function of the trigeminal nerve, which results in loss of corneal sensation, poor healing, and risk of corneal scarring or perforation. OXERVATE is the first and only targeted pharmacological treatment that addresses the underlying nerve deficiency by delivering recombinant human nerve growth factor directly to the ocular surface.
Apply one drop to the affected eye six times per day, at approximately two-hour intervals during waking hours. The full course lasts eight weeks. Wash your hands, remove contact lenses, tilt your head back, and place the drop into the lower eyelid pocket without touching the eye. Each multidose vial is used for one day only and must be discarded at the end of that day. Leave at least 15 minutes between OXERVATE and any other eye drops, and apply eye ointments or gels last.
In the pivotal REPARO and NGF0214 clinical trials, signs of corneal healing were often visible within the first four weeks of treatment, and complete healing was most commonly achieved by the end of the eight-week course. Approximately 65–72% of patients treated with OXERVATE achieved complete corneal healing at eight weeks, compared with 29–43% of patients receiving vehicle eye drops. Most healed patients maintained healing over 12 months of follow-up. Individual response varies, and your ophthalmologist will monitor progress at regular visits.
OXERVATE contains a recombinant human protein (cenegermin) that is sensitive to temperature, light, and oxidation. Freezing at -20°C preserves the biological activity of the protein over its shelf life. Once thawed, the weekly supply remains stable in the refrigerator for up to 14 days, and each daily vial is stable at room temperature for up to 12 hours of in-use time. Refreezing is not allowed because repeated freeze-thaw cycles damage the protein and would reduce efficacy.
OXERVATE was originally authorised for adults aged 18 years and older. Subsequent paediatric studies and label updates in some jurisdictions have supported use in children and adolescents aged two years and above with moderate or severe neurotrophic keratitis, using the same regimen as adults. OXERVATE should not be used in children under two years of age. Use in children must be supervised by a paediatric ophthalmologist or cornea specialist experienced in the condition, and will depend on local approvals.
Yes, but timing is important. Leave at least 15 minutes between OXERVATE and any other eye drop. Apply eye ointments or gels last, because they can block absorption of subsequent drops. Preservative-free artificial tears and autologous serum eye drops are commonly used alongside OXERVATE and are generally well tolerated. Preservative-containing eye drops (particularly those with benzalkonium chloride), topical corticosteroids, and topical NSAIDs should be minimised where possible, because they can impair corneal healing.
Eye pain is the most frequently reported side effect and affects more than 1 in 10 patients, usually in the first days or weeks of treatment. In most cases the pain is mild to moderate, transient, and improves as the cornea heals. Interestingly, because neurotrophic keratitis itself is characterised by reduced corneal sensation, some patients actually perceive returning sensation as pain – a sign that nerve regeneration is occurring. Persistent, severe, or rapidly worsening pain should always be reported to your ophthalmologist.
If the cornea has not completely healed after an initial eight-week course, your ophthalmologist may consider a second course. Limited clinical and real-world data suggest that retreatment can be beneficial in some patients, particularly those who achieved partial but incomplete healing. However, retreatment should only be undertaken after a careful risk-benefit assessment and is not a substitute for treating underlying causes such as uncontrolled herpes keratitis, severe dry eye, or lid abnormalities.
References
- European Medicines Agency (EMA). OXERVATE (cenegermin) – Summary of Product Characteristics and European Public Assessment Report. Last updated 2024. Available from: EMA EPAR.
- U.S. Food and Drug Administration (FDA). OXERVATE (cenegermin-bkbj) Prescribing Information. Revised 2024. Available from: FDA Drug Label.
- Bonini S, Lambiase A, Rama P, Sinigaglia F, Allegretti M, Chao W, Mantelli F, REPARO Study Group. Phase II Randomized, Double-Masked, Vehicle-Controlled Trial of Recombinant Human Nerve Growth Factor for Neurotrophic Keratitis. Ophthalmology. 2018;125(9):1332–1343. doi:10.1016/j.ophtha.2018.02.022.
- Pflugfelder SC, Massaro-Giordano M, Perez VL, et al. Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial (NGF0214). Ophthalmology. 2020;127(1):14–26. doi:10.1016/j.ophtha.2019.08.020.
- Mastropasqua L, Nubile M, Lanzini M, Calienno R, Dua HS. In vivo confocal microscopy evaluation of corneal reinnervation after treatment with cenegermin in patients with neurotrophic keratitis. Cornea. 2020;39(3):311–317.
- Dua HS, Said DG, Messmer EM, et al. Neurotrophic keratopathy. Prog Retin Eye Res. 2018;66:107–131.
- American Academy of Ophthalmology (AAO). Preferred Practice Pattern: Cornea/External Disease – Bacterial Keratitis and Corneal Epithelial Defects. 2024.
- Versura P, Giannaccare G, Pellegrini M, Sebastiani S, Campos EC. Neurotrophic keratitis: current challenges and future prospects. Eye Brain. 2018;10:37–45. doi:10.2147/EB.S117261.
- Sacchetti M, Lambiase A. Neurotrophic factors and corneal nerve regeneration. Neural Regen Res. 2017;12(8):1220–1224.
- World Health Organization (WHO). International Nonproprietary Names (INN) for Pharmaceutical Substances: Cenegermin. WHO Drug Information; 2016.
- Mackie IA. Neuroparalytic keratitis. In: Fraunfelder FT, Roy FH, Meyer SM, editors. Current Ocular Therapy. Philadelphia: WB Saunders; 1995:452–454.
- Sheha H, Tighe S, Hashem O, Hayashida Y. Update on cenegermin eye drops in the treatment of neurotrophic keratitis. Clin Ophthalmol. 2019;13:1973–1980.
Editorial Team
This article was written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians with expertise in ophthalmology, cornea and ocular surface disease, and clinical pharmacology.
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