Severe Neurotrophic Keratitis Research Articles

The use of rh-NGF in the management of neurotrophic keratopathy

Neurotrophic keratitis or keratopathy (NK) is a degenerative corneal disease induced by impairment of the trigeminal nerve function. This condition may lead to persistent epithelial defects, corneal ulceration, and perforation. The diagnosis of NK requires a careful investigation of any ocular and systemic condition associated with the disease and ocular surface and corneal sensitivity examinations. In the past, several medical and surgical procedures were used to treat this condition with different clinical effectiveness. Cenegermin is a recombinant human nerve growth factor (rh-NGF) that supports corneal reinnervation. Different clinical trials have demonstrated the safety and efficacy of topical cenegermin in patients with moderate to severe neurotrophic keratitis. In this review, we report the literature on clinical results regarding the treatment of NK with cenegermin since its approval by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in 2017 and 2018, respectively.

Protonthérapie haute énergie des tumeurs extra-oculaires, kératite neurotrophique et conséquence fonctionnelle : une série de 3 cas

High energy proton therapy (HEP) is a form of radiation therapy using protons for extraocular tumors. Its ballistic properties are theoretically advantageous, but the real impact on the surrounding ocular tissues during cerebral and ENT irradiation is poorly documented. We describe three consecutive patients with corneal damage following such irradiation. Post-proton therapy neurotrophic keratitis (NK) is defined as corneal hypo/anesthesia responsible for an alteration of corneal trophicity and graded according to the Mackie classification, in terms of a prospective ophthalmological follow-up protocol for all patients with extraocular tumors treated with HEP. Among 193 patients treated with HEP between 2018 and 2021 for extraocular tumors, three patients developed severe neurotrophic keratitis, i.e. 1.6% of treated patients. According to the Mackie classification, the three patients showed grade 3 NK less than one year after the conclusion of their HEP. These three patients underwent amniotic membrane grafting. They were placed on autologous serum eye drops. Two of the three patients had to be eviscerated. The dose to the cornea was greater than 50 Gray (Gy)_Relative biological effectiveness (RBE) in the three cases. The diagnosis and etiological origin of neurotrophic keratitis are often difficult to establish. In these cases, the imputability of radiation therapy, proton therapy in our cases, in the development of neurotrophic keratitis was plausible based on the dosimetry of the patients, all of whom had anterior tumors with a poor prognosis requiring high tumoricidal doses. Further studies to establish the impact of proton therapy on corneal sensitivity are necessary. However, this feedback and the multidisciplinary management of tumors can help to limit the risk of some complications of radiation therapy. Early diagnosis allows for appropriate management and could possibly minimize the anatomical and functional ocular complications of neurotrophic keratitis.

Cenegermin (Oxervate)


 CADTH recommends that Oxervate be reimbursed by public drug plans for the treatment of moderate to severe neurotrophic keratitis (NK) in adult patients if certain conditions are met.
 Oxervate should only be covered to treat patients who have never been treated with Oxervate before and have previously tried but failed conventional nonsurgical therapies.
 Oxervate should only be reimbursed if prescribed by a cornea specialist experienced in the management of NK or by an ophthalmologist when comanaging the patient with a cornea specialist. Oxervate should not be prescribed along with preservative-containing topical antibiotics and/or antiviral eye drops. The cost of Oxervate should be reduced.

Clinical and instrumental assessment of the corneal healing in moderate and severe neurotrophic keratopathy treated with rh-NGF (Cenegermin).

To evaluate corneal healing in patients with moderate and severe neurotrophic keratitis (NK) treated with topical rh-NFG (Cenegermin). Twenty-one patients (12F and 9M) aged from 21 to 93 years (62.5 ± 19.4) with moderate and severe NK were enrolled in the study. The patients were divided into 2 groups accordingly to the severity of the disease. The underlying causes of NK were determined. The VAS questionnaire was dispensed. The ocular examination comprised slit lamp evaluation, ocular surface assessment with Keratograph 5M (Oculus, Germany), corneal sensitivity with Cochet-Bonnet esthesiometer (Lunneaux, France) and corneal thickness measurement with AC-OCT (DRI, Triton, Topcon, Japan). The drops of Cenegermin 0.002% were administrated 6 times daily for 8 weeks. All participants were evaluated at baseline, after 4 and 8 weeks of the treatment. The area of corneal defect with maximum diameter less than 0.5 mm was considered as healed. The main outcome measures were corneal healing, corneal sensitivity recovery and corneal thickness in the ulcer group. The herpetic keratitis was the most common cause of NK. Thirteen eyes were affected by severe grade of NK with corneal ulcer and 8 eyes presented a moderate grade. After 8 weeks a complete healing of the corneal defects was registered both in moderate and severe NK. Significant increase of the corneal sensitivity and thickness were registered. The rh-NGF (Cenegermin) resulted effective in the treatment of the severe and moderate NK with significant recovery of the corneal sensitivity and healing of the corneal defects in both groups.

REC 0/0559 Eye Drops for Treatment of Moderate and Severe Neurotrophic Keratitis in Adult Patients

REC 0/0559 Eye Drops for Treatment of Moderate and Severe Neurotrophic Keratitis in Adult Patients

En-Bloc Resection Versus Resection After Evacuation and Suction of the Content for Orbital Optic Nerve Glioma Causing Visual Loss and Disfiguring Proptosis.

To evaluate the surgical outcomes of two different techniques of resection for optic nerve gliomas confined to the intra-orbital segment. This prospective, comparable, clinical interventional case series was conducted at the orbital clinic of Assiut University Hospital, the referral centre of Upper Egypt in the period between 2006 and 2018. The study included 10 children with optic nerve gliomas confined to the intra-orbital part without intracanalicular or intracranial extension and causing severe visual loss and disfiguring proptosis. In all cases, lateral orbitotomy was performed to expose the mass. In 5 cases (group A), the glioma was resected en-bloc. In 5 cases (group B), a new technique of resection was introduced. The wall of the glioma was incised, the content was evacuated and suctioned and followed by resection under good visualization of the markedly reduced mass in size. In the 2 groups, no tumour regrowth was reported during the follow-up period of 3-12 years. In group A, the 5 cases developed postoperative third nerve damage with paralytic ptosis and one case had severe neurotrophic keratitis ended by dense corneal opacity. In group B, a healthy ipsilateral eye was preserved in all cases and no one case developed postoperative paralytic ptosis. Reduction of size of an intra-orbital optic nerve glioma by evacuation and suction of the content before resection is highly recommended. This makes the surgical field during resection more visible and minimizes the possibility of third or other nerves damage.

Update On Cenegermin Eye Drops In The Treatment Of Neurotrophic Keratitis.

Neurotrophic keratitis is an underdiagnosed degenerative condition induced by impairment to the corneal nerves which may lead to persistent epithelial defects and corneal blindness. Current medical and surgical treatments are only supportive and poorly tackle the underlying problem of corneal anesthesia; hence, fail to provide a permanent cure. Cenegermin is a newly introduced recombinant human nerve growth factor (rhNGF) that may address this issue. Preliminary clinical trials have demonstrated the safety and efficacy of topical cenegermin in patients with moderate to severe neurotrophic keratitis; however, the clinical experience with this drug is still limited. This review summarizes the pathogenesis and management of neurotrophic keratitis as well as the mechanism of action, uses, and limitations of cenegermin eye drops in the treatment of neurotrophic keratitis.

Amniotic Membrane Transplantation and Fibrin Glue in the Management of Corneal Ulcers and Perforations

To evaluate the efficacy of amniotic membrane in corneal ulcers refractive to conventional treatment and amniotic membrane with fibrin glue in corneal perforations. Amniotic membrane transplantation (AMT) was performed in 33 eyes from 32 patients for corneal ulcers refractive to conventional treatment. Fourteen ulcers were perforated and received fibrin glue and amniotic membrane. Ulcers were divided into 3 groups: neurotrophic or exposure, autoimmune, and other etiology. Overall success was observed in 80% (27/33 eyes) of the cases, with success rates of 87.5% (14/16 eyes), 70% (7/10 eyes), 85.7% (6/7 eyes) in groups 1, 2, and 3, respectively. The ulcers healed in a mean time of 3.6 +/- 1.6 weeks and the follow-up was 14.8 +/- 9.9 months. Failure was noted in 6 eyes with severe neurotrophic keratitis, Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and Acanthamoeba keratitis. Grafts with fibrin sealant showed a success rate of 92.9 % (13/14 eyes) compared to 73.7% (14/19 eyes) for amniotic grafts alone. In patients with severe limbal damage, a success rate of only 20% (1/5) was observed. AMT is a viable option in the treatment of nonhealing corneal ulcers of various depth and etiologies. Perforations up to 3 mm can be safely managed by fibrin glue and AMT. These techniques lead to rapid reconstruction of the corneal surface and can give a good final functional result or allow keratoplasty to be done in more favorable conditions.

Topical treatment with nerve growth factor for neurotrophic keratitis

Objective To evaluate the efficacy of nerve growth factor (NGF) in patients with neurotrophic keratitis. Design Prospective, noncomparative, interventional case series. Participants Forty-five eyes of 43 consecutive patients with moderate (stage 2, n = 17) to severe (stage 3, n = 28) neurotrophic keratitis unresponsive to other nonsurgical therapies. Methods After a 10-day washout with preservative-free artificial tears, 45 eyes with neurotrophic keratitis received murine NGF (200 μg/ml) every 2 hours for 2 days followed by one drop six times daily until the ulcer healed. A maintenance dose of one drop NGF (100 μg/ml) was administered four times daily for the 2 weeks subsequent to ulcer healing. Main outcome measures Size and depth of the ulcer or the epithelial defect, corneal sensitivity, best corrected visual acuity, side effects, and relapse of the disease in the follow-up period. Results All patients had a complete resolution of the persistent epithelial defect (with or without an ulcer) after 12 days to 6 weeks of treatment with NGF. Patients affected by both stages of the disease demonstrated both improved corneal sensitivity and visual acuity (P < 0.001). No significant differences were observed in the time to complete corneal healing between stage 2 and stage 3 patients. Hyperemia and ocular and periocular pain were side effects reported during the first days of treatment. No relapse of the disease was observed during the follow-up period, with the exception of three patients with trigeminal nerve resection, who required a single retreatment. Conclusions Nerve growth factor eye drops improved corneal sensitivity and promoted corneal epithelial healing in both moderate and severe neurotrophic keratitis. Although performed in an uncontrolled and nonrandomized series of patients, this therapy shows promise for the restoration of ocular surface integrity and visual function in neurotrophic corneal disease.

Multilayer amniotic membrane transplantation for reconstruction of deep corneal ulcers

Purpose To evaluate the efficacy of multilayer amniotic membrane transplantation for reconstruction of corneal epithelium and stroma in the context of deep corneal ulcers. Design Prospective, noncomparative, interventional case series. Participants Eleven consecutive patients with deep corneal ulcers refractory to conventional treatment; six patients had herpetic keratitis and five had other forms of neurotrophic keratitis. Intervention Multilayer amniotic membrane transplantation with kryopreserved human amniotic membrane. Main outcome measures Integrity of corneal epithelium and stroma, opacification, and appearance of grafted membrane during 12 months follow-up. Results Amniotic membrane transplantation markedly reduced ocular inflammation in all patients. Epithelium healed above all corneal ulcers within 4 weeks and remained stable in 9 of 11 patients for 1 year. Two patients with recurrent epithelial defect suffered from severe neurotrophic keratitis. Following transplantation the amniotic membranes gradually dissolved over a period of 12 months, but stromal thickness remained stable. Conclusion Amniotic membrane transplantation allows corneal surface reconstruction in patients with persistent epithelial defects. The multilayer technique is useful for treating deep corneal ulcers and even descemetoceles. Because the procedure results in stability of the ocular surface over a period of more than 12 months in most patients, it may be considered an alternative to conventional surgical techniques for ocular surface reconstruction.