Is pre-operative electromyography a reliable tool in differentiating acute and chronic facial palsy? A preliminary evaluation in patients treated with triple innervation facial reanimation.

Electromyographic evaluation is a reliable tool for confirming facial palsy and assessing its severity. It allows differentiating facial paresis and paralysis, and further distinguishes acute palsies, still showing muscle fibrillations, from chronic cases. This article aims to show that EMG fibrillations might represent a better criterion to differentiate acute and chronic palsies than the standard 18-24 months' cut-off usually employed for classification and treatment purposes. We performed a cohort study using the eFACE tool for comparing triple innervation facial reanimation results in patients with EMG fibrillation treated <12 months, 12-18 months, and >18 months from paralysis onset. Patients showed a statistically significant post-operative improvement in all eFACE items, both in the whole sample and in the three groups. Only the deviation from the optimal score for the gentle eye closure item in group 2 didn't reach statistical significance (p = 0.173). The post-operative results were comparable in the three groups, as the Kruskal-Wallis test showed a difference only for the platysmal synkinesis item scores, which were significantly lower in group 3 (p = 0.025).

Insights on the Choice and Preparation of the Donor Nerve in Corneal Neurotization for Neurotrophic Keratopathy: A Narrative Review.

The article introduces neurotrophic keratopathy (NK), a condition resulting from corneal denervation due to various causes of trigeminal nerve dysfunctions. Surgical techniques for corneal neurotization (CN) have evolved, aiming to restore corneal sensitivity. Initially proposed in 1972, modern approaches offer less invasive options. CN can be performed through a direct approach (DCN) directly suturing a sensitive nerve to the affected cornea or indirectly (ICN) through a nerve auto/allograft. Surgical success relies on meticulous donor nerve selection and preparation, often involving multidisciplinary teams. A PubMed research and review of the relevant literature was conducted regarding the surgical approach, emphasizing surgical techniques and the choice of the donor nerve. The latter considers factors like sensory integrity and proximity to the cornea. The most used are the contralateral or ipsilateral supratrochlear (STN), and the supraorbital (SON) and great auricular (GAN) nerves. Regarding the choice of grafts, the most used in the literature are the sural (SN), the lateral antebrachial cutaneous nerve (LABCN), and the GAN nerves. Another promising option is represented by allografts (acellularized nerves from cadavers). The significance of sensory recovery and factors influencing surgical outcomes, including nerve caliber matching and axonal regeneration, are discussed. Future directions emphasize less invasive techniques and the potential of acellular nerve allografts. In conclusion, CN represents a promising avenue in the treatment of NK, offering tailored approaches based on patient history and surgical expertise, with new emerging techniques warranting further exploration through basic science refinements and clinical trials.

The extracapsular dissection technique in the management of benign tumours of the parotid gland: our experience in 194 patients.

OBJECTIVE: The indications for and approaches to extracapsular dissection for parotid gland benign tumours are debated in the literature. This study retrospectively evaluates a single site's short- and long-term results with a standardised extracapsular dissection approach to benign parotid tumours. METHODS: A retrospective review of a single institution's records identified cases with extracapsular dissection as the primary surgery for non-recurrent benign parotid tumours. A total of 194 eligible patients were identified (124 women and 70 men, age 47.75 ± 15.62 years). Pre-, intra- and post-surgical data were reviewed for complications and recurrences. RESULTS: Histology reported pleomorphic adenoma in 165 patients, Warthin's tumour in 28 patients and both in one patient. Mean follow up was 36 ± 16 months (range, 12-84 months). The incidences of complications following extracapsular dissection were temporary (n = 13) and permanent (n = 0) facial nerve dysfunction, Frey's syndrome (n = 1)) and recurrences (n = 5). These rates align with prior literature. CONCLUSION: This case series shows how a standardised approach to extracapsular dissection for benign parotid tumours yields favourable results, supporting a progressive change of strategy towards reduced invasiveness.

Research trends and perspectives on immediate facial reanimation in radical parotidectomy (Review).

For patients diagnosed with advanced malignant parotid tumour, radical parotidectomy with facial nerve sacrifice is part of the treatment. Multiple surgical techniques have been developed to cure facial paralysis in order to restore the function and aesthetics of the face. Despite the large number of publications over time on facial nerve reanimation, a consensus on the timing of the procedure or the donor graft selection has remained to be established. Therefore, the aim of the present study was to conduct a bibliometric analysis to identify and analyse scientific publications on the reconstruction of the facial nerve of patients who underwent radical parotidectomy with facial nerve sacrifice. The analysis on the topic was conducted using the built-in tool of the Scopus database and VOSviewer software. The first 100 most cited articles were separately reviewed to address the aim of the study. No consensus was found regarding the recommended surgical techniques for facial nerve reanimation. The most used donor cranial nerves for transfer included the following: Masseteric branch of the V nerve, contralateral VII nerve with cross-face graft, the XI nerve and the XII nerve. The best timing of surgery is also controversial depending on pre-exiting pathology and degree of nerve degeneration. However, most of the clinical experience suggests facial nerve restoration immediately after the ablative procedure to reduce complications and improve patients' quality of life.

Intra-surgical optimized identification of masseteric nerve for central facial nerve neurorrhaphy: A retrospective study.

It is the aim of the study to provide a detailed intraoperative assessment of the masseteric nerve and the facial branch of the smiling muscles complex through the same superficial musculoaponeurotic system (SMAS) incision. This observational retrospective study aimed to define the straightest and safest surgical route to identify the facial nerve for the smiling muscles complex and the masseteric nerve, using distance from the tragus and zygomatic arch as anatomical landmarks. 30 patients were included in the study. The mean distance from the tragus to the masseteric nerve was 40.03 mm, the mean distance from the zygomatic arch was 12.24 mm, and the mean depth from the SMAS was 10.84 mm. Data were consistent, with little variation. The distance from the zygoma was found to be higher in male patients. There was a positive correlation between the depth to the nerve and the distance from the zygoma, but no correlation between body mass index and the other parameters studied. Within the limitations of the study it seems that the proposed standardized direct approach to the masseteric nerve is a reproducible technique that may be used to increase the safety of the procedure, reduce the operating time, and decrease the amount of dissection and related postoperative scarring, thereby fostering positive results.

Periocular management in recent facial palsy patients treated with triple innervation technique: A retrospective case series.

Facial paralysis decreases eye protection mechanisms leading to ocular problems up to corneal ulceration, and blindness. This study aimed to evaluate the outcomes of periocular procedures for recent facial paralysis. Medical records of patients with unilateral recent complete facial palsy who did periocular procedures at the Maxillofacial Surgery Department of San Paolo Hospital (Milan, Italy) between April 2018 and November 2021 were retrospectively reviewed. 26 patients were included. All patients were evaluated 4 months after surgery. The first group included 9 patients who underwent upper eye lid lipofilling and midface suspension with fascia lata graft; they had no ocular dryness symptoms and no need for eye protection measures in 33.3% of cases, significant reduction of ocular symptoms and need for eye protection measures in 66.6% of patient, 0-2 mm lagophthalmos in 66.6% and 3-4 mm lagophthalmos in 33.3%. The second group of 17 patients who underwent upper eyelid lipofilling, midface suspension with fascia lata graft and lateral tarsorrhaphy, had no ocular dryness symptoms and no need for eye protection measures in 17.6% of patient, significant reduction of ocular symptoms and need for eye protection measures in 76.4% of patient, 0-2 mm lagophthalmos in 70.5%, 3-4 mm lagophthalmos in 23.5% and one patient 5,8%had 8 mm lagophthalmos and persistent symptoms. No ocular complication, cosmetic complain or donner site morbidity were reported. Upper eyelid lipofilling, midface suspension with fascia lata graft and lateral tarsorrhaphy decrease ocular dryness symptoms and need for eye protection measures and improve lagophthalmos: the association of the reinnervation with these complementary techniques is therefore highly recommended in order to immediately protect the eye.

Buccally or Lingually Tilted Implants in the Lateral Atrophic Mandible: A Three-Year Follow-Up Study Focused on Neurosensory Impairment, Soft-Tissue-Related Impaction and Quality of Life Improvement.

Background and Objectives: In the severely resorbed posterior mandible, implant placement requires either bone regenerative procedures, subperiosteal implants or short implant placement with drawbacks including morbidity and increased treatment costs and duration. To overcome these inconveniences, some unconventional alternatives have been suggested, such as buccally or lingually tilted implants in the lateral mandible, bypassing the inferior alveolar nerve. The aim of the present retrospective study was to evaluate the three-year survival rate of implants inserted in the posterior atrophic mandible, bypassing the inferior alveolar nerve. The assessment was focused on the occurrence of postoperative complications related to neurosensory impairment and soft tissue impaction, as well as overall improvement in quality of life. Materials and Methods: Patients with severe bone atrophy in the lateral area of the mandible were included in the present study. Only the implants tilted either buccally or lingually to bypass the inferior alveolar nerve were analysed. The relation between peri-implant soft tissue and the healing abutment was assessed and a secondary revision surgery was performed when indicated. The Semmes-Weinstein pressure neurological test was used for qualitative assessment of inferior alveolar nerve function and the Geriatric Oral Health Assessment Index (GOHAI) was used for evaluating Oral-Health-Related Quality of Life (OHRQoL). Results: Fourteen implants were placed in nine patients during the evaluation period. Survival rate was 100%, temporary paraesthesia occurred in one patient and a limited definitive paraesthesia was seen in another patient. Mild or significant discomfort related to soft tissue impaction with healing abutment was observed in six out of nine patients. A statistically significant OHRQoL improvement was observed in all patients. Conclusions: Despite the limited number of patients and observation time, insertion of implants buccally or lingually bypassing the inferior alveolar nerve is a predictive treatment option for patients with severe bone atrophy in the posterior mandible.

Sural Nerve Vertical Cross-Face Graft for Lacrimal Gland Neurotization to Improve Tear Secretion in Neurodeprivative Dry Eye.

PURPOSE: No specific interventions have been reported for the treatment of severe neurodeprivative dry eye disease owing to facial nerve palsy. We describe herein the feasibility of a novel surgical procedure to reinnervate the lacrimal gland and report the preliminary outcomes of the first series of patients who were treated accordingly. METHODS: Prospective interventional case series including consecutive patients affected by facial palsy with absolute deficiency of tear secretion who underwent lacrimal gland neurotization. A sural nerve vertical cross-face graft was used to connect the lacrimal gland with the parasympathetic branch of the lingual nerve directed to the contralateral submandibular gland. RESULTS: Lacrimal neurotization was performed uneventfully in 10 patients (4 M, 6 F; mean age 47.1 ± 17.1 years). In all cases, the procedure was combined with facial reanimation, while corneal neurotization was performed in 4 cases. One year postoperatively, mean values of a Schirmer test increased significantly compared with baseline values (7.56 ± 7.84 vs. 0 ± 0 mm/5 min; P = 0.02), while the mean daily number of instillation of tear substitutes decreased significantly (21.8 ± 4.5 vs. 7.1 ± 2.2; P = 0.009). Overall, all patients were satisfied with surgery (very satisfied: n = 7 and satisfied: n = 2). No major postoperative complications occurred. CONCLUSIONS: Vertical cross-face using a sural nerve graft to connect the lacrimal gland with the contralateral submandibular gland is a novel technique for treating patients with facial nerve palsy and severe neurodeprivative dry eye disease. This surgery both performed alone and combined with corneal neurotization is able to improve tear secretion and decrease the need for frequent instillations of tear substitutes.

Wide Range Applications of Spirulina: From Earth to Space Missions.

Spirulina is the most studied cyanobacterium species for both pharmacological applications and the food industry. The aim of the present review is to summarize the potential benefits of the use of Spirulina for improving healthcare both in space and on Earth. Regarding the first field of application, Spirulina could represent a new technology for the sustainment of long-duration manned missions to planets beyond the Lower Earth Orbit (e.g., Mars); furthermore, it could help astronauts stay healthy while exposed to a variety of stress factors that can have negative consequences even after years. As far as the second field of application, Spirulina could have an active role in various aspects of medicine, such as metabolism, oncology, ophthalmology, central and peripheral nervous systems, and nephrology. The recent findings of the capacity of Spirulina to improve stem cells mobility and to increase immune response have opened new intriguing scenarios in oncological and infectious diseases, respectively.

Validation of a Cleanroom Compliant Sonication-Based Decellularization Technique: A New Concept in Nerve Allograft Production.

Defects of the peripheral nervous system are extremely frequent in trauma and surgeries and have high socioeconomic costs. If the direct suture of a lesion is not possible, i.e., nerve gap > 2 cm, it is necessary to use grafts. While the gold standard is the autograft, it has disadvantages related to its harvesting, with an inevitable functional deficit and further morbidity. An alternative to autografting is represented by the acellular nerve allograft (ANA), which avoids disadvantages of autograft harvesting and fresh allograft rejection. In this research, the authors intend to transfer to human nerves a novel technique, previously implemented in animal models, to decellularize nerves. The new method is based on soaking the nerve tissues in decellularizing solutions while associating ultrasounds and freeze-thaw cycles. It is performed without interrupting the sterility chain, so that the new graft may not require post-production γ-ray irradiation, which is suspected to affect the structural and functional quality of tissues. The new method is rapid, safe, and inexpensive if compared with available commercial ANAs. Histology and immunohistochemistry have been adopted to evaluate the new decellularized nerves. The study shows that the new method can be applied to human nerve samples, obtaining similar, and, sometimes better, results compared with the chosen control method, the Hudson technique.

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.

PSI-Guided Mandible-First Orthognathic Surgery: Maxillo-Mandibular Position Accuracy and Vertical Dimension Adjustability.

In orthognathic surgery, patient-specific osteosynthesis implants (PSIs) represent a novel approach for the reproduction of the virtual surgical planning on the patient. The aim of this study is to analyse the quality of maxillo-mandibular positioning using a hybrid mandible-first mandibular-PSI-guided procedure on twenty-two patients while the upper maxilla was fixed using manually bent stock titanium miniplates. The virtual surgical plan was used to design PSIs and positioning guides, which were then 3D printed using biocompatible materials. A Cone Beam Computed Tomography (CBCT) scan was performed one month after surgery and postoperative facial skeletal models were segmented for comparison against the surgical plan. A three-dimensional cephalometric analysis was carried out on both planned and obtained anatomies. A Spearman correlation matrix was computed on the calculated discrepancies in order to achieve a more comprehensive description of maxillo-mandibular displacement. Intraoperatively, all PSIs were successfully applied. The procedure was found to be accurate in planned maxillo-mandibular positioning reproduction, while maintaining a degree of flexibility to allow for aesthetics-based verticality correction in a pitch range between -5.31 and +1.79 mm. Such a correction did not significantly affect the achievement of planned frontal symmetry.

Preliminary Study with the Use of a Titanium Mesh as Space Maker and Implant Primary Stabilization for One-Stage Sinus Lift in Cases with Less Than 1.5 mm Residual Bone.

(1) Background: In the lateral area of the maxilla, the alveolar bone can lose significant volume due to maxillary sinus pneumatization following teeth extractions. This preliminary study evaluated the effectiveness of a novel technique for one-stage sinus lifting and simultaneous implant placement in cases with less than 1.5 mm residual alveolar bone. The subsequent survival rate at 1-year post-occlusal loading was assessed. (2) Methods: 15 patients were selected, the main inclusion criteria were the partially edentulous area in the posterior maxilla with alveolar bone height of less than 1.5 mm below the sinus. All of the patients underwent one-stage sinus lifting, along with simultaneous implant placement using a "butterfly" anchorage device to optimize the primary stability and xenograft bone as graft material. At 6 to 9 months after surgery, the anchorage device was removed and implants were loaded. Panoramic x-ray images were used to assess the new bone formation, while the biological stability was measured using resonance frequency analysis. (3) Results: 15 implants were inserted. The mean implant stability quotient (ISQ) value was 71.3 (SD = ±2.51) and the mean healing period was 7.3 (SD = ±1.23) months. The mean bone height after the healing period was 14.4 (SD = ±2.05). A statistically significant correlation was found between the healing period and the ISQ value (Spearman rho = 0.684, sig. = 0.005). No statistically significant correlation was found between the ISQ value and the new regenerated bone height (Person r = 0.389, sig. = 0.152). Smoking was identified as a risk factor involved in postoperative complications. (4) Conclusions: The results of the present preliminary study demonstrated that the proposed "butterfly" technique was effective when performing one-stage sinus lifting and simultaneous implant placement in cases with less than 1.5 mm of residual alveolar bone. The survival rate was 100% at 1-year post occlusal loading.

Use of CAD-CAM Bridging Mandibular Prosthesis in Osteonecrosis of the Jaw: The Experience of Our School.

Osteonecrosis of the jaw (ONJ) is a disease that affects the jaw. It is mainly related to radiation or bisphosphonates therapy, and the symptoms and signs consist of pain, bone exposure, inflammation of the surrounding soft tissue swelling, and secondary infection or drainage. In the case of advanced disease of the mandibular area, the treatment of choice is mandibular resection and reconstruction. In the present study, we report a case series of patients affected by ONJ and treated with a customised bridging mandibular prosthesis-only technique. From 2016 to 2018, we treated five consecutive patients affected by ONJ: three patients were affected by biphosphonate-related osteonecrosis of the mandible (BRONJ) and two were affected by osteoradionecrosis of the mandible (ORNJ). Three patients needed a soft tissue free flap to permit optimal wound closure, intra- and/or extraorally. All reconstructive procedures were carried out successfully, with no major or minor microvascular complication. The average postoperative follow-up was 24.8 (range 10-41) months. Considering that microvascular bone transfer is a high-risk procedure in BRONJ patients, we can conclude that the positioning of a customised bridging mandibular prosthesis (CBMP), whether or not associated with a microvascular soft tissue transfer, is a safe technique in terms of surgical outcome and feasibility.

'Butterfly': a residual bone independent technique for one-stage sinus lift.

A 29-year-old woman with an extreme pneumatisation of the maxillary sinus and a missing molar was treated with one-stage sinus lifting and implant placement in a novel surgical approach.

Direct Versus Indirect Corneal Neurotization for the Treatment of Neurotrophic Keratopathy: A Multicenter Prospective Comparative Study.

PURPOSE: To analyze the comparative safety and efficacy of two techniques of corneal neurotization (CN) (direct corneal neurotization [DCN] vs indirect corneal neurotization [ICN]) for the treatment of neurotrophic keratopathy (NK). DESIGN: Multicenter interventional prospective comparative case series. METHODS: This study took place at ASST Santi Paolo e Carlo University Hospital, Milan; S.Orsola-Malpighi University Hospital, Bologna; and Santa Maria alle Scotte University Hospital, Siena, Italy. The study population consisted of consecutive patients with NK who underwent CN between November 2014 and October 2019. The intervention procedures included DCN, which was was performed by transferring contralateral supraorbital and supratrochlear nerves. ICN was performed using a sural nerve graft. The main outcome measures included NK healing, corneal sensitivity, corneal nerve fiber length (CNFL) measured by in vivo confocal microscopy (IVCM), and complication rates. RESULTS: A total of 26 eyes in 25 patients were included: 16 eyes were treated with DCN and 10 with ICN. After surgery, NK was healed in all patients after a mean period of 3.9 months without differences between DCN and ICN. Mean corneal sensitivity improved significantly 1 year after surgery (from 3.07 to 22.11 mm; P < .001) without differences between the 2 groups. The corneal sub-basal nerve plexus that was absent before surgery in all patients, except 4, become detectable in all cases (mean CNFL: 14.67 ± 7.92 mm/mm2 1 year postoperatively). No major complications were recorded in both groups. CONCLUSIONS: CN allowed the healing of NK in all patients as well as improvement of corneal sensitivity in most of them thanks to nerve regeneration documented by IVCM. One year postoperatively, DCN and ICN showed comparable outcomes.

Surgical Management of Primary Chronic Osteomyelitis of the Jaws: The Use of Computer-Aided-Design/Computer-Aided Manufacturing Technology for Segmental Mandibular Resection.

The term osteomyelitis of the jaws identifies different pathological patterns characterized by the involvement of the cortical bone and bone marrow in osteoarticular infections.At the head and neck level, the segment most affected by osteomyelitis is the mandible and in most of the cases the cause of the infection is bacterial, as a result of pulp or periodontal infections, post-extraction alveolitis, foreign bodies and fractures. The mandibular PCO often presents with an insidious onset, without a striking acute phase, and it is characterized by recurrent episodes of pain, swelling, lockjaw, latero-cervical lymphadenopathy, without signs of suppuration.Three patients have been collected and recorded for the study.The authors believe that in the more advanced cases of PCO in adult patients, in which the mandibular bone appears almost entirely sclerotic and deformed, and that are not responsive to pharmacological therapy or to conservative surgical therapies such as decortication, it is necessary to perform a complete removal of the portion affected by osteomyelitis, with lower alveolar nerve preservation and contextual reconstruction with free microvascular bone flap.Our review aims to describe the clinico-pathological features of a rare pathological entity, propose a surgical treatment algorithm using computer-aided-design/computer-aided manufacturing technology and review the existing literature.

In Vivo and Ex Vivo Comprehensive Evaluation of Corneal Reinnervation in Eyes Neurotized With Contralateral Supratrochlear and Supraorbital Nerves.

PURPOSE: To use an automated morphometric analysis system of in vivo confocal microscopy (IVCM) images for evaluating reinnervation occurring at the subbasal nerve plexus (SNP) after direct corneal neurotization (DCN) and to further report neurophysiological and histopathological findings. METHODS: Prospective interventional case series including 3 eyes with neurotrophic keratitis that underwent DCN. Deep anterior lamellar keratoplasty was performed 18 months after DCN in patient 1. The following evaluations were performed before and at 3, 6, and 12 months after DCN: clinical evolution of keratitis; corneal sensitivity; IVCM images of the SNP analyzed with "ACCMetrics;" neurophysiological study of corneal reflex. Protein gene product 9.5 immunofluorescence staining assay and transmission electron microscopy were conducted on the neurotized button excised during deep anterior lamellar keratoplasty. RESULTS: Complete healing was obtained in all patients by 3 months postoperatively. Corneal sensitivity was absent preoperatively in all eyes and improved after surgery, reaching an average value of 30 mm 1 year postoperatively. The corneal SNP was not visible at IVCM in any of the cases preoperatively and became visible by 3 months postoperatively, showing IVCM metrics comparable to normal contralateral eyes at 1 year. In all cases, neurophysiological evaluation showed a partial recovery of the electrical activity of the cornea. In patient 1, protein gene product (PGP) 9.5 staining of neurotized cornea showed nerve fascicles at the SNP, whereas transmission electron microscopy showed amyelinic nerve axons and nerve endings. CONCLUSIONS: The corneal SNP exhibited IVCM metrics comparable to the normal contralateral eye 1 year after DCN. Ex vivo histopathological assessment of neurotized corneas confirmed the presence of nerves with normal ultrastructure.

Auto-Allo Graft Parallel Juxtaposition for Improved Neuroregeneration in Peripheral Nerve Reconstruction Based on Acellular Nerve Allografts.

INTRODUCTION: Nerve repair poses a significant surgical challenge, and much research on this topic for improvement in reconstruction of segmental defects is ongoing. The aims of the study were to reconfirm the accuracy and safety of a previously described nerve decellularization method on a larger experimental population of rabbits, as well as on human nerves, and to establish in vivo the efficacy of a new-concept mixed graft, comprising autologous and acellular nerve allograft components within the same graft. METHODS: Acellular nerve allografts were implanted into tibial nerve defects of 5 rabbits (group A), autografts were implanted, representing the criterion standard, in other 5 animals (group B), and the innovative technique was used in the remaining 5 (group C). Twelve weeks postoperatively, nerve conduction evaluations were performed; animals were euthanatized, and grafts were harvested and morphologically, histomorphometrically, and immunohistochemically analyzed. Eventually, a preliminary in vitro validation of the decellularization method was performed on human nerves from a cadaver. RESULTS: No clinical adverse effect was revealed during all the experimental times. No tissue reaction was observed, and in all groups, regenerated fascicles and bundles were shown by histology. However, both histology and histomorphometry demonstrated a better regenerative efficiency in group C. The morphological evaluation of the human nerve treated with the novel method showed complete decellularization. CONCLUSION: The microsurgical combined model demonstrated a better neuroregeneration than did pure autografts and acellular nerve allografts. The decellularization method seemed effective also on human nerves. Deeper investigations are necessary to further validate and transfer this new encouraging protocol to the clinical arena.

Longitudinal Morphometric Analysis of Sub-Basal Nerve Plexus in Contralateral Eyes of Patients with Unilateral Neurotrophic Keratitis.

Objectives: To investigate longitudinally corneal sub-basal nerve plexus (SNP) by means of in vivo confocal microscopy (IVCM) in the contralateral eye (CE) of patients with unilateral neurotrophic keratitis (NK) secondary to central nervous system (CNS) diseases who underwent different treatments. Methods: Ten patients with NK and 10 matched controls were included. In 7 NK patients, conservative treatment maintained unchanged the clinical picture over the 1-year follow-up (Group 1), while NK progressed in 3 patients who underwent direct corneal neurotization (Group 2). IVCM scans of SNP of NK patients were acquired in CE at baseline (V0) ad after 1-year follow-up (V1). All images were analyzed with the automated software "ACCMetrics" and compared with controls. The following IVCM corneal nerve parameters were calculated at V0 and V1 with ACCMetrics: fiber density (CNFD), branch density (CNBD), fiber length (CNFL), total branch density (CTBD), fiber area (CNFA), fiber width (CNFW), and fractal dimension (CNFrD). Results: At V0, significantly lower mean values of CNFD and CNBD, and higher values of CNFW were detected in CE of NK patients compared to controls (respectively, 16.9 ± 8.7 vs 25.0 ± 8.3 n/mm2, P= .029; 19.3 ± 13.8 vs 33.8 ± 18.9 n/mm2, P= .023; 0.022 ± 0.002 vs 0.020 ± 0.001 mm/mm2, P< .001). From V0 to V1, all IVCM metrics of CE remained unchanged in Group 1, while they improved in Group 2. Conclusions: Contralateral eye of patients with unilateral NK secondary to CNS disease showed lower CNFD and CNBD and higher CNFW compared to controls. Unlike conservative treatment, direct corneal neurotization was able to improve SNP metrics also in CE.