Long-Term Outcome of Unilateral Acoustic Neuromas With or Without Hearing Loss: Over 10 Years and Beyond After Gamma Knife Radiosurgery.

BACKGROUND: Since the long-term outcomes of 162 patients who underwent gamma knife radiosurgery (GKS) as an initial or adjuvant treatment for acoustic neuromas (ANs) with unilateral hearing loss were first reported in 1998, there has been no report of a comprehensive analysis of what has changed in GKS practice. METHODS: We performed a retrospective study of the long-term outcomes of 106 patients with unilateral sporadic ANs who underwent GKS as an initial treatment. The mean patient age was 50 years, and the mean initial tumor volume was 3.68 cm3 (range, 0.10-23.30 cm3). The median marginal tumor dose was 12.5 Gy (range, 8.0-15.0 Gy) and the median follow-up duration was 153 months (range, 120-216 months). RESULTS: The tumor volume increased in 11 patients (10.4%), remained stationary in 27 (25.5%), and decreased in 68 patients (64.2%). The actuarial 3, 5, 10, and 15-year tumor control rates were 95.3 ± 2.1%, 94.3 ± 2.2%, 87.7 ± 3.2%, and 86.6 ± 3.3%, respectively. The 10-year actuarial tumor control rate was significantly lower in the patients with tumor volumes of ≥ 8 cm3 (P = 0.010). The rate of maintaining the same Gardner-Robertson scale grade was 28.6%, and that of serviceable hearing was 46.4%. The rates of newly developed facial and trigeminal neuropathy were 2.8% and 4.7%, respectively. The patients who received marginal doses of less than 12 Gy revealed higher tumor control failure rates (P = 0.129) and newly occurred facial or trigeminal neuropathy rates (P = 0.040 and 0.313, respectively). CONCLUSION: GKS as an initial treatment for ANs could be helpful in terms of tumor control, the preservation of serviceable hearing, and the prevention of cranial neuropathy. It is recommended to perform GKS as soon as possible not only for tumor control in unilateral ANs with hearing loss but also for hearing preservation in those without hearing loss.

Semiscleral Contact Lens Use After Direct Corneal Neurotization for Neurotrophic Keratopathy.

PURPOSE: To describe a case of a patient treated for neurotrophic keratopathy (NK) with direct corneal neurotization (CN), where a modification to the CN technique allowed for semiscleral contact lens use postoperatively. OBSERVATION: Our patient had successful CN with improved corneal sensation. During the procedure, a 1.0 mm gutter was created between the limbus and nerve graft to allow for semiscleral contact lens fitting. CONCLUSIONS: With the use of preoperative planning and a limbal gutter during CN, a semiscleral contact lens can serve as a well-tolerated postoperative management option to improve visual acuity and protect the corneal surface in patients with NK.

Postoperative trigeminal neuropathy outcomes following surgery for tumors involving the trigeminal nerve.

OBJECTIVE: To observe the evolution and outcomes of postoperative trigeminal neuropathy following surgery of tumor involving the trigeminal nerve. METHODS: A prospective observational study was conducted between October 2018 and February 2019 involving 25 patients with tumors confirmed to involve the trigeminal nerve during surgery by senior author. Pre- and postoperative trigeminal nerve function status and clinical data were recorded. RESULTS: This study included 18 cases of meningioma and seven of trigeminal schwannoma. Among the meningioma cases, 55.6% of the patients reported facial sensory dysfunction before surgery, 33.3% presented ocular discomfort, and 5.6% had masticatory muscle atrophy. Postoperatively, all patients experienced facial paresthesia, 94.4% complained of eye dryness, and one (5.56%) exhibited keratitis. Additionally, one patient (5.56%) showed new-onset masticatory weakness. During follow-up, 50.0% of patients reported improvement in facial paresthesia, and one (5.56%) experienced deterioration. Eye dryness resolved in 35.3% of patients, and keratitis remission was observed in one patient. However, one patient (5.56%) developed neurotrophic keratitis. Overall, 55.6% of patients displayed mild masticatory weakness without muscle atrophy. In the cases of schwannoma, 28.6% of patients had facial paresthesia before surgery, 42.9% showed ocular discomfort, and one (14.3%) complained of masticatory dysfunction. Postoperatively, 85.7% of patients reported facial paresthesia and eye dryness, with one patient (16.7%) experiencing keratitis. During follow-up, 66.7% of patients demonstrated improvement in facial paresthesia, 28.6% showed eye dryness remission, and one patient (16.7%) recovered from keratitis. However, one patient (16.7%) developed new-onset neurotrophic keratitis. One patient (16.7%) experienced relief of masticatory dysfunction, but 42.9% reported mild deterioration. Another patient (14.3%) had facial anesthesia that had not improved. CONCLUSION: Postoperative trigeminal neuropathy is a common complication with a high incidence rate and poor recovery outcomes after surgery for tumors involving the trigeminal nerve. When trigeminal nerve damage is unavoidable, it is essential to provide a multidisciplinary and careful follow-up, along with active management strategy, to mitigate the more severe effects of postoperative trigeminal neuropathy.

Bilateral Corneal Neurotization for Ramos-Arroyo Syndrome and Developmental Neurotrophic Keratopathy: Case Report and Literature Review.

PURPOSE: The purpose of this study was to report the use of bilateral corneal neurotization for neurotrophic keratitis in the setting of Ramos-Arroyo syndrome. METHODS: The case report and surgical technique are described in detail in this article, as well as a review of the literature on corneal neurotization for congenital corneal anesthesia. RESULTS: We report a 17-year-old patient who underwent bilateral corneal neurotization for neurotrophic keratitis secondary to corneal anesthesia in Ramos-Arroyo syndrome. Corneal neurotization was performed with great auricular nerve transfers extended by sural nerve autografts. CONCLUSIONS: We present the treatment of neurotrophic keratopathy with corneal neurotization in a patient with Ramos-Arroyo syndrome. We describe how bilateral corneal neurotization using the great auricular nerve technique is a safe and effective procedure for patients with congenital/developmental corneal anesthesia.

Two-Stage Resection of a Giant Trigeminal Schwannoma in a Non-Neurofibromatosis Type 2 Pediatric Patient: A Case Report, Systematic Review, and Intraoperative Video.

BACKGROUND: Trigeminal schwannoma is an uncommon tumor in pediatric patients. Several surgical approaches have been described in the literature. METHODS: The case of an 11-year-old boy with a giant dumbbell-shaped trigeminal schwannoma removed through a 2-stage approach was presented with an intraoperative video. Using PubMed and Scopus, the literature on trigeminal schwannoma in pediatric patients was searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. RESULTS: The search strategy yielded 312 titles, of which 13 were included in the review. Cases of trigeminal schwannoma were described, with a highly variable clinical presentation and anatomical arrangement in cranial fossae. Two-stage approaches were reported, although most studies described single-stage approaches. Common postoperative outcomes were a range of disturbances of cranial nerve V. CONCLUSIONS: The surgical approach varies based on the tumor conformation. However, a 2-stage pterional subtemporal and semisitting retrosigmoid approach is a safe, practical, and effective strategy for the removal of dumbbell-shaped trigeminal schwannoma in a pediatric patient.

Corneal neurotization in the management of neurotrophic keratopathy: A review of the literature.

Neurotrophic keratopathy (NK) is a rare degenerative disease in which damage to the corneal nerves leads to corneal hypoesthesia or anesthesia. Neurotrophic corneal ulcers are notoriously difficult to treat and can lead to blindness. Corneal neurotization (CN) is a recent surgical technique aimed at restoring corneal sensation and may offer a definitive treatment in the wake of NK. Herein, we review the surgical techniques utilized in direct and indirect CN. Technical considerations, outcomes, current limitations and future perspectives are also discussed. This article highlights the key points of this promising procedure and biological aspects that will help provide the best treatment options for patients with severe NK.

Thirty-year clinical experience in gamma knife radiosurgery for trigeminal schwannomas.

We aimed to evaluate the radiographic and clinical outcomes after gamma knife radiosurgery (GKRS) for trigeminal schwannomas (TSs). A total of 87 patients who underwent GKRS for TSs between 1990 and 2020 were enrolled. The mean tumor volume was 4.3 cm3. The median prescribed dose for the margins of the tumor was 13 Gy. The median follow-up duration was 64.3 months (range 12.0-311.5 months). The overall local tumor control rate was 90%, and the symptom response rate was 93%. The response rate for each symptom was 88% for facial pain, 97% for facial sensory change, and 86% for cranial nerve deficits. Nineteen (22%) patients showed transient swelling, which had regressed at the time of the last follow-up. Cystic tumors were associated with transient swelling (p = 0.04). A tumor volume of < 2.7 cm3 was associated with local tumor control in univariable analysis. Transient swelling was associated with symptom control failure in both univariable and multivariable analyses (p = 0.04, odds ratio 14.538). GKRS is an effective treatment for TSs, both for local control and symptom control.

Pediatric benign triton tumor of trigeminal nerve: a case report and literature review.

PURPOSE: Benign triton tumors (BTTs) in the pediatric population are extremely rare occurrences. Paucity of data on BTTs poses both diagnostic and therapeutic challenges, particularly when found intracranially. METHODS: A case report of a 10-year-old male diagnosed with incidental maxillary trigeminal (V2) BTT is presented. We discuss radiographic and histopathological interpretations. Furthermore, we provide a brief review of current literature and historical background on pediatric trigeminal BTT diagnosis, histopathology, and management. RESULTS: Successful gross total resection of the tumor was achieved via Dolenc approach to the cavernous sinus. Management options with consideration of outcomes from the few prior cases reported in the literature are presented. CONCLUSION: Treatment of trigeminal nerve tumors requires a broad differential diagnosis and understanding rare tumors is essential in the diagnosis and treatment algorithm.

Sustained Release of Tacrolimus From a Topical Drug Delivery System Promotes Corneal Reinnervation.

Purpose: Corneal nerve fibers provide sensation and maintain the epithelial renewal process. Insufficient corneal innervation can cause neurotrophic keratopathy. Here, topically delivered tacrolimus is evaluated for its therapeutic potential to promote corneal reinnervation in rats. Methods: A compartmentalized neuronal cell culture was used to determine the effect of locally delivered tacrolimus on sensory axon regeneration in vitro. The regenerating axons but not the cell bodies were exposed to tacrolimus (50 ng/mL), nerve growth factor (50 ng/mL), or a vehicle control. Axon area and length were measured after 48 hours. Then, a biodegradable nanofiber drug delivery system was fabricated via electrospinning of a tacrolimus-loaded polycarbonate-urethane polymer. Biocompatibility, degradation, drug biodistribution, and therapeutic effectiveness were tested in a rat model of neurotrophic keratopathy induced by stereotactic trigeminal nerve ablation. Results: Sensory neurons whose axons were exposed to tacrolimus regenerated significantly more and longer axons compared to vehicle-treated cultures. Trigeminal nerve ablation in rats reliably induced corneal denervation. Four weeks after denervation, rats that had received tacrolimus topically showed similar limbal innervation but a significantly higher nerve fiber density in the center of the cornea compared to the non-treated control. Topically applied tacrolimus was detectable in the ipsilateral vitreal body, the plasma, and the ipsilateral trigeminal ganglion but not in their contralateral counterparts and vital organs after 4 weeks of topical release. Conclusions: Locally delivered tacrolimus promotes axonal regeneration in vitro and corneal reinnervation in vivo with minimal systemic drug exposure. Translational Relevance: Topically applied tacrolimus may provide a readily translatable approach to promote corneal reinnervation.

[Treatment of neurotrophic keratopathy in combined lesions of the trigeminal and facial nerves]. / Lechenie neirotroficheskoi keratopatii pri sochetannom porazhenii troinichnogo i litsevogo nervov.

Ocular symptomatology in lesions of the facial nerve is associated with disturbed innervation of the circular muscle of the eye that leads to disruption of the protective function of the eyelids and the development of exposure symptoms, and is accompanied by a breach in corneal tear film integrity. The main clinical manifestation of the trigeminal nerve damage is the loss of sensory innervation of the cornea and disruption of the supply of neurotransmitters to its cells, manifesting as corneal hypo- or anesthesia. This triggers a cascade of pathological processes that lead to the development of neurotrophic keratopathy. In combined pathology of the facial and trigeminal nerves, a number of interrelated and mutually aggravating problems arise that require correction of lagophthalmos and functional restoration of the trigeminal nerve, since there is an interaction between the corneal epithelium and trigeminal neurons through trophic neuromodulators, which normally contribute to the proliferation of epithelial cells, their differentiation, migration and adhesion, and are essential for vital functions, metabolism and healing of surface lesions of the eye. Classical methods of treating neurotrophic keratopathy aim to protect the ocular surface, and are palliative or auxiliary, do not provide radical relief of the symptoms of neurotrophic keratopathy. Modern surgical technique of neurotization of the cornea allows restoring the structural growth of the nerve, which provides nerve trophism and corneal sensitivity, and is the only pathogenetically substantiated method of effective treatment of neurotrophic keratopathy. At the same time, direct neurotization has undeniable advantages over methods involving intercalary donor nerves, since neuropeptides from nerve fibers are immediately released into the recipient tissue and start reparative processes. Taking into account the accumulated positive experience of neurotization surgeries, scientific and clinical research should be continued in order to improve the most effective methods of corneal neurotization and promote their wider implementation into clinical practice.

Neurotrophic keratopathy: current challenges and future prospects.

Neurotrophic keratopathy (NK), or neurotrophic keratitis, is a degenerative condition that results from decreased innervation to the cornea. The cornea is innervated by the ophthalmic branch of the trigeminal nerve. Neurotrophic keratopathy is most commonly caused by herpes keratitis however, any condition that disrupts the normal corneal innervation can cause NK. Neurotrophic keratopathy is a clinical diagnosis and is classified into three stages based on the disease severity. Stage 1 has mild epithelial defects, such as punctate keratopathy, stage 2 disease has persistent epithelial defects, and stage 3 is defined by the presence of ulcers. Current treatment modalities consist of medical and surgical options. Stage 1 is treated with lubrication through artificial tears, eyelid taping, and punctal plug/cautery. Stage 2 treatment can involve therapeutic contact lenses, topical autologous or allogenic serum, tarsorrhaphy, botulinum toxin injections, and possibly anti-inflammatory medications. Stage 3 disease may require human nerve growth factor, amniotic membrane transplantation, conjunctival flap, or corneal neurotization. New therapies, such as matrix regenerating therapy, plasma rich in growth factors, Thymosin ß4, Substance P/Insulin like growth factor-1, and nicergoline represent exciting future options.KEY MESSAGESNeurotrophic keratopathy is a rare degenerative disease defined by decreased innervation to the cornea that is associated with significant morbidity.Treatment options range from lubrication alone to various medical and surgical treatments.Matrix regenerating therapy, plasma rich in growth factors, Thymosin ß4, Substance P/Insulin like growth factor-1, and nicergoline are exciting novel therapies that will influence how neurotrophic keratopathy is treated in the future.

Clinical Outcomes of Minimally Invasive Corneal Neurotization After Cerebellopontine Angle Neurosurgical Procedures.

PURPOSE: To report 12 patients with neurotrophic keratopathy due to the trigeminal nerve injury after intracranial tumor surgeries underwent minimally invasive corneal neurotization and evaluate the outcomes of corneal reinnervation. METHODS: Twelve patients (12 eyes) with neurotrophic keratopathy caused by the trigeminal nerve injury after intracranial surgeries received minimally invasive corneal neurotization. All the preoperative central corneal sensation was under 5 mm, and minimally invasive corneal neurotization was performed over 6 months after the intracranial surgery. Follow-up was conducted 1 week and 1 month after the surgery and then every 3 months. Twelve healthy age-matched participants were enrolled as controls. The indicators included corneal sensation, best-corrected visual acuity, corneal nerve fiber length and branch density, diameter of nerve trunk, corneal ulcer lesion ratio, and sensation of the contralateral forehead. RESULTS: Mean follow-up was 24.7 ± 7.1 months. Mean central corneal sensation rose from 0.4 ± 1.4 to 31.7 ± 21.8 mm. Corneal nerve fiber length improved from 9.56 ± 5.00 to 14.96 ± 4.65 mm/mm2 and corneal nerve branch density and diameter of nerve trunk both increased (p < .01 and p < .05, respectively). Corneal lesion ratio decreased from 0.17 ± 0.12 to 0.10 ± 0.10 (p < .01). CONCLUSIONS: Minimally invasive corneal neurotization promotes corneal reinnervation for patients with neurotrophic keratopathy induced by the trigeminal nerve injury after intracranial surgeries. The process of corneal reinnervation after minimally invasive corneal neurotization often lasts over 12 months, and it takes about 18 months to return to a higher level. Corneal sensation and corneal nerve fiber length are related to clinical outcomes such as corneal ulcer lesion and best-corrected visual acuity. The effect on the sensation of the contralateral side forehead is temporary, and most patients can restore normal forehead sensation of the contralateral side.

Neurotrophic Keratitis in a Pediatric Patient With Goldenhar Syndrome and Trigeminal Aplasia Successfully Treated by Corneal Neurotization.

Herein, the authors report an unusual case of a 6-year-old boy with right-sided Goldenhar syndrome and trigeminal nerve aplasia who developed neurotrophic keratopathy (NK). Despite the use of therapeutic contact lenses and multiple temporary tarsorrhaphy, NK worsened showing a central corneal scar, neovascularization, and significant stromal thinning, with risk of corneal perforation. Cochet-Bonnet esthesiometry revealed complete corneal anesthesia. To minimize additional corneal complications, the patient underwent indirect corneal neurotization by a sural nerve autograft anastomosed to the contralateral supratrochlear nerve. At 24-month follow up, no epithelial defects, complications, or recurrence were observed. Significant improvements in corneal sensitivity with esthesiometry score of 20 mm and reflex blinking were achieved. This case highlights corneal anesthesia should be suspected among Goldenhar syndrome ophthalmologic abnormalities and monitored before corneal changes become irreversible. Since corneal neurotization can successfully improve corneal sensation, it could be considered as an early therapeutic option to avoid refractory NK.

Corneal Neurotization Using the Great Auricular Nerve for Bilateral Congenital Trigeminal Anesthesia.

PURPOSE: The purpose of this study was to describe an indirect corneal neurotization (CN) technique for congenital bilateral trigeminal anesthesia using the greater auricular nerve (GAN) as a donor. METHOD: CN was performed to preserve the integrity of the only seeing eye in a 4-year-old boy with pontine tegmental cap dysplasia and bilateral trigeminal anesthesia. He had recurrent corneal ulceration and scarring despite full medical treatment. The GAN was used as a donor, and the sural nerve was harvested and used as a bridge which was tunneled to the sub-Tenon space in the inferior fornix. The fascicles were distributed into the 4 quadrants and sutured to the sclera near the limbus. RESULT: This technique resulted in providing corneal sensation and improving stability of the epithelium. Corneal opacity gradually decreased allowing significant visual improvement evidenced in the early postoperative months. CONCLUSIONS: Using the GAN technique for CN bypasses trigeminal innervation and has the potential to improve corneal sensation. The GAN is a large caliber nerve and provides a large amount of axons and robust neurotization. This technique would be desirable for cases with bilateral congenital trigeminal anesthesia, such as pontine tegmental cap dysplasia.

Corneal Neurotization: A Novel Surgical Procedure for Neurotrophic Keratopathy.

PURPOSE: The aim of this study is to describe techniques, results, and open issues of corneal neurotization (CN) for the treatment of neurotrophic keratopathy (NK). METHODS: An overview of the most important studies of CN is provided. The 2 main surgical approaches (namely, direct CN and indirect CN) with specific advantages and disadvantages are described. The results regarding changes of corneal sensitivity and clarity, visual acuity, and in vivo confocal microscopy metrics are summarized. Ex vivo studies with histopathology of the neurotized cornea are reported. Intraoperative and early and late postoperative complications are described along with current open issues to be further clarified. RESULTS: Corneal sensitivity improves after both direct and indirect CN. Corneal reinnervation allows the healing of NK in almost the totality of the operated eyes, determining a corresponding improvement of corneal clarity and visual acuity. Regeneration of corneal nerve fibers is confirmed by means of either in vivo confocal microscopy or ex vivo histopathology. Few self-limiting complications are reported during the postoperative course. Current open issues concern the identification of the technique of choice, the use of autograft or allograft, and the timing of CN either when performed alone or when combined with other surgeries. CONCLUSIONS: CN represents a game-changing surgical procedure for NK, which has the potential to restore corneal sensitivity in all stages of the disease regardless of the mechanism of denervation. Further long-term results are needed to confirm its efficacy over time. The design of randomized clinical trials comparing CN with noninterventional therapies could further validate the adoption of this technique.

Outcomes of corneal neurotisation using processed nerve allografts: a multicentre case series.

BACKGROUND: Corneal neurotisation is a rapidly evolving procedure treating neurotrophic keratopathy. The variety of surgical techniques used and corresponding outcomes after corneal neurotisation are not well understood. This study describes the techniques and outcomes in the largest case series of corneal neurotisation using processed nerve allografts to date. METHODS: This is a retrospective case series of patients who underwent corneal neurotisation with human cadaveric processed nerve allografts. All patients had preoperative and postoperative description of best corrected visual acuity and measurement of corneal sensation. Comparative studies after stratification of techniques were performed. RESULTS: A total of 17 patients were identified. The cause of corneal anaesthesia was prior infection in eight cases, trigeminal nerve palsy in eight cases and ocular trauma in one case. There were no intraoperative or postoperative complications. Following neurotisation surgery, the time to first gain of corneal sensation and maximal gain of sensation occurred at a mean of 3.7 months (range 1-8 months) and 6.6 months (range 3-15 months), respectively. The mean preoperative and postoperative corneal sensation as measured by Cochet-Bonnet aesthesiometry was 0.36 cm (range 0-3.2 cm) and 4.42 cm (range 0-6 cm), respectively (p<0.01). Visual acuity was unchanged after neurotisation. There were no statistical differences in outcomes based on end-to-end versus end-to-side coaptations, donor nerve selection or laterality of donor nerve. CONCLUSION: Corneal neurotisation with processed nerve allografts is a safe and effective procedure. This study provides further evidence for the use of processed nerve allografts for corneal neurotisation.

Microsurgical Resection of Trigeminal Schwannoma via Anterior Petrosal Approach: 2-Dimensional Operative Video.

Trigeminal schwannomas are complex lesions that may be related to many critical neurovascular structures. We present the case of a 59-year-old male presenting a history of left-sided trigeminal neuralgia. Preoperative imaging demonstrated a mass highly suggestive of a trigeminal schwannoma, and microsurgical resection was indicated considering the progressive symptomatology and important mass effect (Video 1). A middle fossa route including an anterior petrosectomy was chosen. The patient was placed supine with the head rotated to the contralateral side, and an arcuate incision was performed. A V-shaped zygomatic osteotomy was done to mobilize the temporalis muscle more inferiorly and better expose the middle fossa floor. Following craniotomy, peeling of the dura propria from the lateral wall of cavernous sinus was carried out starting by coagulation of middle meningeal artery. Some tumor was already identified and removed, and then the anterior petrosectomy was performed until we exposed the posterior fossa dura. The middle fossa dural incision was connected with the other one at the posterior fossa dura, by coagulation of the superior petrosal sinus. The tentorium was completely cut toward the incisura. After lesion debulking, the tumor was progressively removed by peeling the arachnoid from the lesion to maintain arachnoid planes and preserve the nerves and their blood supply. Postoperative imaging demonstrated complete tumor resection. The patient's symptoms improved, and there were no neurologic deficits on follow-up. Extensive laboratory training is fundamental to be familiarized with the normal anatomic nuances and prepared to face the anatomy distorted by lesion. Informed consent was obtained from the patient for the procedure and publication of this operative video.

Corneal and Facial Sensory Neurotization in Trigeminal Anesthesia.

Trigeminal anesthesia may yield blindness and facial disfigurement, secondary to neurotrophic keratopathy and trigeminal trophic syndrome. This article summarizes contemporary medical and emerging surgical approaches for the therapeutic management of this rare and devastating disease state.

Seeing through the evidence for corneal neurotization.

PURPOSE OF REVIEW: Trigeminal anesthesia causes neurotrophic keratopathy, which may yield facial disfigurement and corneal blindness. RECENT FINDINGS: We summarize approaches and evidence for corneal neurotization. SUMMARY: Regional sensory nerve transfer appears safe and effective for therapeutic management of neurotrophic keratopathy. Prospective randomized clinical trials are necessary to confirm the utility of corneal neurotization.