Endoscopic endonasal approach for resection of odontoid process, decompression of the cervicomedullary junction spinal cord, and resection of pannus.

Odontoid pannus is an abnormal collection of degenerative or inflammatory tissue on the C1-dens joint that can result in severe spinal cord compression myelopathy. Treatment options vary depending on severity and etiology. In cases of severe cord compression, surgical management could be either through a purely posterior approach or in combination with an anterior decompression via endoscopic endonasal approach (EEA). This case presents a 77-year-old female who underwent posterior cervical fixation for odontoid pannus causing dramatic cervical myelopathy who failed to improve over a 6-month period and required anterior transodontoid pannus resection and decompression via EEA. The video can be found here: https://stream.cadmore.media/r10.3171/2024.1.FOCVID23176.

Late-onset prosthetic aortic valve stenosis caused by pannus formation.

Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to an open surgical aortic valve replacement (SAVR) for treating severe symptomatic aortic stenosis. Despite gaining widespread acceptance and approval for use in patients with high, moderate, and low surgical risk, the increasing use of TAVR has raised concerns about potential short- and long-term complications. We present the case of a 69-year-old female who underwent TAVR and subsequently presented to our outpatient cardiology clinic with progressively worsening dyspnea, orthopnea, and paroxysmal nocturnal dyspnea two years after the procedure. Echocardiography and stress testing revealed a recurrence of aortic stenosis, leading to a diagnosis of structural valve deterioration. The patient was subsequently scheduled for SAVR, which revealed commissural fusion, scarring, and unusual pannus formation that significantly narrowed the effective valve area, necessitating valve replacement. Despite requiring SAVR, two years after TAVR, the patient had a favorable postoperative course and outcome on follow-up. This case underscores the importance of continued surveillance and evaluation of patients who undergo TAVR, as they remain at risk for long-term complications such as structural valve deterioration. Proper management, including timely diagnosis and intervention, can lead to successful outcomes in such patients. Learning objective: This case underscores the importance of continued surveillance and evaluation of patients who undergo transcatheter aortic valve replacement, as they remain at risk for long-term complications such as structural valve deterioration. Proper management, including timely diagnosis and intervention, can lead to successful outcomes in such patients.

Corneal pannus, Herbert's pits and conjunctival inflammation in older children in Papua New Guinea.

PURPOSE: The prevalence of trachomatous inflammation-follicular (TF) in Papua New Guinea (PNG) suggests antibiotic mass drug administration (MDA) is needed to eliminate trachoma as a public health problem but the burden of trichiasis is low. As a result, WHO issued bespoke recommendations for the region. If ≥ 20% of 10-14-year-olds have both any conjunctival scarring (C1 or C2 or C3) and corneal pannus and/or Herbert's pits, MDA should be continued. Equally, if ≥ 5% of that group have both moderate/severe conjunctival scarring (C2 or C3) and corneal pannus and/or Herbert's pits, MDA should be continued. METHODS: We identified 14 villages where > 20% of 1-9-year-olds had TF during baseline mapping undertaken 4 years and 1 month previously. Every child aged 10-14 years in those villages was eligible to be examined for clinical signs of corneal pannus, Herbert's pits and conjunctival scarring. A grading system that built on existing WHO grading systems was used. RESULTS: Of 1,293 resident children, 1,181 (91%) were examined. Of 1,178 with complete examination data, only one (0.08%) individual had concurrent scarring and limbal signs. CONCLUSIONS: The WHO-predefined criteria for continuation of MDA were not met. Ongoing behavioural and environmental improvement aspects of the SAFE strategy may contribute to integrated NTD control. Surveillance methods should be strengthened to enable PNG health authorities to identify future changes in disease prevalence.

Successful treatment of a rheumatoid arthritis patient with severe synovial hypertrophy and impaired shoulder function with microwave ablation technique.

Rheumatoid arthritis (RA) is a chronic, inflammatory systemic disorder of synovial joints and results in polyarthritis, chronical degeneration, and finally deformities and ankylosis in severe cases. Synovitis and pannus formation are results of inflammatory changes and lead into restriction in joint movement. Shoulders are among the later affected and larger joints and formation of synovitis in early active stages and pannus in later stages might be concluded with frozen shoulder and severe impairment in functionality. These late-term changes cannot be controlled with systemic or local anti-inflammatory agents and synovectomy is chosen in some cases. However, the results are not satisfactory and recurrence is common. In this case report, we presented a case of RA with severe shoulder pain, restricted movement due to synovial hypertrophy, and pannus formation which are resistant to local and systemic interventions and not suitable for surgical or chemical synovectomy. Microwave ablation (MWA) was performed successfully without any complication and she well responded in terms of DAS-28, functional, and pain scores. Range of motion and funcitonal restriction were recovered. This case report describes the use and promising results of MWA in RA with severe synovial hypertrophy and pannus formation even in the absence of active arthritis and effusion. MWA is a safe and minimally invasive technique that can be easily performed in coordinance of rheumatologists and interventional radiologists in proper cases.

A novel classification and management scheme for craniocervical junction disorders with ventral neural element compression.

OBJECTIVE: Craniocervical junction (CCJ) pathologies with ventral neural element compression are poorly understood, and appropriate management requires accurate understanding, description, and a more uniform nomenclature. The aim of this study was to evaluate patients to identify anatomical clusters and better classify CCJ disorders with ventral compression and guide treatment. METHODS: A retrospective review of adult and pediatric patients with ventral CCJ compression from 2008 to 2022 at a single center was performed. The incidence of anatomical abnormalities and compressive etiologies was assessed. Surgical approach, radiographic data, and outcomes were recorded. Association rules analysis (ARA) was used to assess variable clustering. RESULTS: Among 51 patients, the main causes of compression were either purely bony (retroflexed dens [n = 18]; basilar invagination [BI; n = 13]) or soft tissue (degenerative pannus [n = 16]; inflammatory pannus [n = 2]). The primary cluster in ARA was a retroflexed dens, platybasia, and Chiari malformation (CM), and the secondary cluster was BI, C1-2 subluxation, and reducibility. These, along with degenerative pannus, formed the three major classes. In assessing the optimal treatment strategy, reducibility was evaluated. Of the BI cases, 12 of the 13 patients had anterolisthesis of C1 that was potentially reducible, compared with 2 of the 18 patients with a retroflexed dens (both with concomitant BI), and no pannus cases. The mean C1-2 facet angle was significantly higher in BI at 32.4°, compared with -2.3° in retroflexed dens and 8.1° in degenerative pannus (p < 0.05). Endonasal decompression with posterior fixation was performed in 48 (94.0%) of the 51 patients, whereas posterior reduction/fixation alone was performed in 3 patients (6.0%). Of 16 reducible cases, open posterior reduction alone was successful in 3 (60.0%) of 5 cases, with all successes containing isolated BI. Reduction was not attempted if vertebral anatomy was unfavorable (n = 9) or the C1 lateral mass was absent (n = 5). The mean follow-up was 28 months. Symptoms improved in 88.9% of patients and were stable in the remaining 11.1%. Tracheostomy and percutaneous G-tube placement occurred in 7.8% and 11.8% of patients, respectively. Reoperation for an endonasal CSF leak repair or posterior cervical wound revision both occurred in 3.9% of patients. CONCLUSIONS: In classifying, one cluster caused decreased posterior fossa volume due to an anatomical triad of retroflexed dens, platybasia, and CM. The second cluster caused pannus formation due to degenerative hypertrophy. For both, endonasal decompression with posterior fixation was ideal. The third group contained C1 anterolisthesis characterized by a steep C1-2 facet angle causing reducible BI. Posterior reduction/fixation is the first-line treatment when anatomically feasible or endonasal decompression with in situ posterior fixation when anatomical constraints exist.

Vertebrobasilar Insufficiency Syndrome in Extension: Insights into Surgical Treatment.

BACKGROUND: Rotational vertebrobasilar artery syndrome, or bow hunter syndrome, is a rare yet well-documented pathology. This study presents a surgical approach to a latent manifestation of dynamic, extension-only, bilateral codominant vertebral artery compression in the V3 segment, associated with craniocervical instability and central canal stenosis. METHODS: The clinical presentation involves the treatment of positional vertigo resulting from left and high-grade right vertebral artery stenosis during neck extension only. Diagnosis was confirmed through a formal angiogram under provocative maneuvers. Surgical intervention, detailed in this section, employed a multidisciplinary approach, including intraoperative angiograms to ensure patent vertebral arteries precraniocervical fusion. RESULTS: The surgical treatment demonstrated success in addressing extension-only vertebrobasilar syndrome and associated complications of C1-2 pannus and craniocervical instability. Intraoperative angiograms confirmed vertebral artery patency pre- and postsurgical positioning, ensuring the effectiveness of the multidisciplinary approach. CONCLUSIONS: This study concludes by highlighting the successful multidisciplinary surgical treatment of a patient with nonunion of a C1 Jefferson fracture, leading to extension-only vertebrobasilar syndrome complicated by C1-2 pannus and craniocervical instability. The importance of considering vertebral artery dynamic stenosis in cases of positional vertigo or transient neurological symptoms following an injury is emphasized. Surgical stabilization, particularly when conservative measures prove ineffective, is recommended, with careful attention to pre- and postsurgical positioning to verify vertebral artery patency and posterior vasculature integrity.

Multifaceted oncostatin M: novel roles and therapeutic potential of the oncostatin M signaling in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a self-immune inflammatory disease characterized by joint damage. A series of cytokines are involved in the development of RA. Oncostatin M (OSM) is a pleiotropic cytokine that primarily activates the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, and other physiological processes such as cell proliferation, inflammatory response, immune response, and hematopoiesis through its receptor complex. In this review, we first describe the characteristics of OSM and its receptor, and the biological functions of OSM signaling. Subsequently, we discuss the possible roles of OSM in the development of RA from clinical and basic research perspectives. Finally, we summarize the progress of clinical studies targeting OSM for the treatment of RA. This review provides researchers with a systematic understanding of the role of OSM signaling in RA, which can guide the development of drugs targeting OSM for the treatment of RA.

[Effect of Juanbi Qianggu Formula on biological behaviors of fibroblast-like synoviocytes in rheumatoid arthritis by regulating FGFR1 signaling pathway based on network pharmacology and cell function experiments].

This study aimed to explore the molecular mechanism of Juanbi Qianggu Formula(JBQGF), an empirical formula formulated by the prestigious doctor in traditional Chinese medicine, in the treatment of rheumatoid arthritis based on network pharmacology and cell function experiments. The main active components and targets of JBQGF were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Encyclopedia of Traditional Chinese Medicine(ETCM), and the core targets underwent functional enrichment analysis and signaling pathway analysis. Cytoscape 3.6.0 was used to construct a visualized "active component-target-signaling pathway" network of JBQGF. After screening, nine potential pathways of JBQGF were obtained, mainly including G protein-coupled receptor signaling pathway and tyrosine kinase receptor signaling pathway. As previously indicated, the fibroblast growth factor receptor 1(FGFR1) signaling pathway was highly activated in active fibroblast-like synoviocytes(FLS) in rheumatoid arthritis, and cell and animal experiments demonstrated that inhibition of the FGFR1 signaling pathway could significantly reduce joint inflammation and joint destruction in collagen-induced arthritis(CIA) rats. In terms of the tyrosine kinase receptor signal transduction pathway, the analysis of its target genes revealed that FGFR1 might be a potential target of JBQGF for rheumatoid arthritis treatment. The biological effect of JBQGF by inhibiting FGFR1 phosphorylation was preliminarily verified by Western blot, Transwell invasion assay, and pannus erosion assay, thereby inhibiting matrix metalloproteinase 2(MMP2) and receptor activator of nuclear factor-κB ligand(RANKL) and suppressing the invasion of fibroblasts in rheumatoid arthritis and erosive effect of pannus bone. This study provides ideas for searching potential targets of rheumatoid arthritis treatment and TCM drugs through network pharmacology.

A fully human monoclonal antibody targeting Semaphorin 5A alleviates the progression of rheumatoid arthritis.

Rheumatoid arthritis (RA) is the most common chronic autoimmune disease worldwide. Although progress has been made in RA treatment in recent decades, remission cannot be effectively achieved for a considerable proportion of RA patients. Thus, novel potential targets for therapeutic strategies are needed. Semaphorin 5A (SEMA5A) plays a pivotal role in RA progression by facilitating pannus formation, and it is a promising therapeutic target. In this study, we sought to develop an antibody treatment strategy targeting SEMA5A and evaluate its therapeutic effect using a collagen-induced arthritis (CIA) model. We generated SYD12-12, a fully human SEMA5A blocking antibody, through phage display technology. SYD12-12 intervention effectively inhibited angiogenesis and aggressive phenotypes of RA synoviocytes in vitro and dose-dependently inhibited synovial hyperplasia, pannus formation, bone destruction in CIA mice. Notably, SYD12-12 also improved the Treg/Th17 imbalance in CIA mice. We confirmed through immunofluorescence and molecular docking that SYD12-12 integrated with the unique TSP-1 domain of SEMA5A. In conclusion, we developed and characterized a fully human SEMA5A-blocking antibody for the first time. SYD12-12 effectively alleviated disease progression in CIA mice by inhibiting pannus formation and improving the Treg/Th17 imbalance, demonstrating its potential for the RA treatment.

Impact of Bileaflet Mechanical Mitral Valve Orientation on Pannus Overgrowth.

OBJECTIVE: Pannus overgrowth is a chronic inflammatory process that can cause valve dysfunction and threaten the durability of prosthetic valves. Bileaflet mechanical mitral valve can be implanted in either an anatomical (parallel to the anatomical axis) or nonanatomical (perpendicular or oblique to the anatomical axis) orientation. The effect of the rotational orientation of the bileaflet mechanical mitral valve on excessive pannus enlargement is unknown. The present study compared the effect of bileaflet mechanical mitral valve orientation on pannus overgrowth. METHODS: The study included patients who underwent bileaflet mechanical mitral valve replacement for rheumatic mitral valve stenosis. The pannus formation was confirmed by reexamining all transesophageal echocardiography images in the picture archiving and communication systems between May 2017 and April 2021. The primary aim of this study was the development of pannus overgrowth. Patients were divided into 2 groups based on their implantation orientation of the bileaflet mechanical mitral valve. RESULTS: Pannus overgrowth was found in 26 patients (56.5%) in the anatomical orientation group and 71 patients (74.7%) in the nonanatomical orientation group (P = 0.03). Anatomical orientation reduced the development of pannus overgrowth (odds ratio [OR] = 0.39, P = 0.04), and double left heart valve replacement increased the development of pannus overgrowth (OR = 2.73, P = 0.04). CONCLUSIONS: Pannus overgrowth was less common in bileaflet mechanical mitral valves implanted in the anatomical orientation.

Prosthetic Aortic Valve Obstruction With Pannus Formation, an Approach for Diagnosis and Management: A Case Report.

Mechanical valve obstructions are critical medical and surgical emergencies that require immediate attention when patients present with new complaints and exhibit signs such as the onset of murmurs or the disappearance of mechanical valve clicks. Obstructions can arise from various causes, including pannus formation, thrombus, vegetations, or subvalvular tissue growth. While pannus formations have been previously reported for the mitral valve, they are less commonly observed in the aortic valve, and several hypotheses have been proposed to understand pannus formation. Accurate diagnosis relies on imaging techniques such as echocardiography and fluoroscopy, and surgical intervention is considered the optimal treatment approach. Here, we present the case of a 69-year-old female who had previously undergone aortic valve replacement and subsequently developed progressive dyspnea, fatigue, and a new onset murmur. Imaging modalities revealed a closed leaflet and a high transvalvular gradient over the valve. The patient underwent a prosthetic redo valve replacement, and post-surgery, she was discharged home without complications.

Bilateral Corneal Panni Associated with Limbal Inclusion Cysts in the Left Eye in a Patient with Atopic Keratoconjunctivitis.

PURPOSE: To report a rare case of atopic keratoconjunctivitis (AKC) presenting with bilateral corneal panni associated with limbal inclusion cysts in the left eye. MATERIALS & METHODS: Retrospective case report. RESULTS: A 19-year-old female with AKC presented with bilateral corneal panni and limbal inclusion cysts in the left eye. Anterior segment swept-source optical coherence tomography showed bilateral hyperreflective epicorneal membrane and a lobulated cystic lesion in the left eye. Ultrasound biomicroscopy demonstrated a dense membrane overriding the cornea in both eyes and hyporeflective spaces separated by medium reflective septa in the cyst. The patient underwent excision of the limbal inclusion cyst and pannus in the left eye. Histopathological examination revealed subepithelial cystic lesion surrounded by non-keratinizing epithelium; areas of acanthosis, hyperkeratosis, parakeratosis, and hyperplasia in the epithelium of the pannus; as well as inflammation, fibrosis, and increase in vascularization in the stroma. CONCLUSION: To our knowledge, this is the first case of corneal pannus associated with limbal inclusion cysts in AKC. Surgical excision was done to establish the diagnosis as well as to improve vision in our case.

Mechanical prosthetic mitral valve obstruction: Pannus or thrombus? A case report.

Substitution of a defective heart valve with a prosthetic heart valve turns the native disease for prosthesis-related complications. One of the most serious and dreaded complications is prosthetic valve obstruction. It is either the result of a thrombus or pannus formation. For the evaluation of prosthetic valve obstruction, transthoracic echography and fluoroscopy provide functional information but may not provide information about the etiology of the obstruction, unlike multidetector computed tomography (MDCT) which allows a more precise etiological diagnosis to guide the therapeutic attitude. Here, we report a case of a mechanical prosthetic mitral valve obstruction in a 45-year-old patient in whom the diagnosis of pannus was retained on the basis of clinical, biological, and imaging data. The differentiation between thrombus and pannus is crucial because it conditions the therapeutic attitude. Advanced imaging specially MDCT options should be considered whenever mechanical prosthesis valve obstruction is suspected.

The Role of CCL3 in the Pathogenesis of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unexplained causes. Its pathological features include synovial tissue hyperplasia, inflammatory cell infiltration in joint cavity fluid, cartilage bone destruction, and joint deformation. C-C motif chemokine ligand 3 (CCL3) belongs to inflammatory cell chemokine. It is highly expressed in inflammatory immune cells. Increasingly, studies have shown that CCL3 can promote the migration of inflammatory factors to synovial tissue, the destruction of bone and joint, angiogenesis, and participate in the pathogenesis of RA. These symptoms indicate that the expression of CCL3 is highly correlated with RA disease. Therefore, this paper reviews the possible mechanism of CCL3 in the pathogenesis of RA, which may provide some new insights for the diagnosis and treatment of RA.

Diagnostic accuracy of two-dimensional and three-dimensional transesophageal echocardiography in detecting pannus and thrombus in left mechanical valve obstruction.

The aim of this study was to determine the accuracy of two-dimensional and three-dimensional transesophageal echocardiography (TEE) in the detection of pannus and thrombus in left mechanical valve obstruction (LMVO) compared with surgical and histopathology findings. Materials and methods: Patients with suspected LMVO on transthoracic echocardiography were enrolled consecutively. All patients underwent two-dimensional and three-dimensional TEE, and open-heart surgery to replace obstructed valves. Macroscopic and microscopic analysis of the excised masses was used as the gold standard for the diagnosis of thrombus and/or pannus. Results: Forty-eight patients [34 women (70.8%), age 49±13 years, New York Heart Association II: 68.8%, New York Heart Association III: 31.2%] were enrolled. In the diagnostic of thrombus, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of three-dimensional TEE were 89.2, 72.7, 85.4, 91.7, and 66.7%, respectively, compared with those of two-dimensional TEE (42.2, 66.7, 43.8, 95, and 7.1%, respectively). In the diagnosis of pannus, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of three-dimensional TEE were 53.3, 100, 85.4, 100, and 82.5%, respectively; compared with those of two-dimensional TEE (7.4, 90.5, 43.8, 50, and 43.2%, respectively). Receiver operating characteristic curves depict that the area under the curves of three-dimensional TEE was higher than the area under the curves of two-dimensional TEE in both diagnoses of thrombus and pannus (0.8560 vs. 0.7330, P=0.0427 and 0.8077 vs. 0.5484, P=0.005, respectively). Conclusions: This study indicated that three-dimensional TEE had a higher diagnostic value than two-dimensional TEE in the detection of thrombus and pannus in patients with LMVO, and can be a reliable imaging modality to identify the causes of LMVO.

Surgical application of Ong speculum in simple limbal epithelial transplantation and pterygium surgery.

Ong speculum is used in glaucoma surgeries such as trabeculectomy to expose the superior part of the globe. The large inferior blade pushes the inferior conjunctival fornix, due to which the eyeball rotates downwards. It has not been used in other anterior segment surgeries before. We used this speculum in simple limbal epithelial transplantation (SLET) and pterygium surgery to expose superior bulbar conjunctiva for harvesting limbal and conjunctival grafts, respectively. As the superior conjunctiva and sclera become exposed, it facilitates the steps of harvesting limbal biopsy and conjunctival graft in SLET and pterygium surgery. This eliminated the need for a superior rectus suture or an assistant who would keep the globe rotated downwards. Its position could also be maneuvered to adjust the site of exposure when dissecting the area of pannus in SLET. Thus, it makes the superior conjunctiva more accessible.

The ratio of measured and reference effective orifice areas for discriminating prosthetic aortic valve obstruction.

AIMS: We aimed to evaluate the efficacy of the measured effective orifice area (EOA)/reference EOA ratio in discriminating mechanical prosthetic aortic valve (PAV) obstruction. METHODS AND RESULTS: This is a retrospective study of 193 mechanical PAV patients with an elevated mean transprosthetic pressure gradient (PG) over 20 mmHg or peak velocity over 3 m/s. Of those, 143 patients were objectively proven PAV obstruction with cardiac computed tomography or surgical inspection. The EOA was measured using the continuity equation, and the reference EOA values were obtained from previous guidelines. The measured/reference EOA ratio was significantly lower in the obstruction group (0.63 ± 0.18 vs. 0.86 ± 0.17; P < 0.001). The EOA ratio added incremental value for discriminating obstruction from the conventional parameters recommended in the guidelines. Receiver operating characteristic curve analysis revealed that the measured/reference EOA ratio discriminated PAV obstruction from those without obstruction [area under the curve (AUC), 0.840; 95% confidence interval, 0.783-0.898; P < 0.001]. A cutoff of 0.71 had 73.4% sensitivity and 82.0% specificity. The novel diagnostic algorithm adding the EOA ratio had similar accuracy to previous guideline algorithms, including reference EOA, and conventional Doppler parameters (AUC, 0.763 vs. 0.731; P = 0.309). In patients with a large PAV (≥23 mm), the novel algorithm had higher accuracy than the previous algorithm (AUC, 0.788 vs. 0.642; P = 0.019). CONCLUSION: The ratio of measured/reference EOA adds incremental value over conventional Doppler parameters and might be helpful for distinguishing PAV obstruction.

Ocular surface lesions in clinical grades of Bell's phenomenon.

Background: Bell's phenomenon, also known as the palpebral oculogyric reflex, is a critical reflex that protects the cornea. We developed an innovative, simple, and practical grading scale for Bell's phenomenon that includes the inverse Bell's phenomenon. Using this scale, we investigated the characteristics of Bell's phenomenon among asymptomatic individuals in different age groups and examined the frequency of ocular surface lesions in asymptomatic and symptomatic participants with different grades. Methods: In this cross-sectional study, we randomly included 330 eyes of 165 asymptomatic, healthy, White Turkish individuals who attended the outpatient eye clinic, with a male-to-female ratio of 1:1.4, in the control group. These were categorized into four age groups: 4 - 20 years, 21 - 40 years, 41 - 60 years, and > 60 years. Eighty eyes from 40 patients with ocular surface lesions and absence of grade + 2 Bell's phenomenon were included in the symptomatic group. Bell's phenomenon was classified into five grades: grade + 2 (strong positive), grade + 1 (weak positive), grade 0 (no Bell's phenomenon, no eye movement), grade -1 (weak inverse), and grade -2 (strong inverse). Results: We detected higher frequencies of grade + 2, + 1, and 0 in individuals aged 4 - 40, 41 - 60, and > 60 years, respectively. There was a significant difference between age groups in the frequencies of different grades (P < 0.001). Pairwise analysis revealed a significantly lower frequency of grade + 2 in the age group > 60 years compared with the 4 - 20 and 21 - 40 year groups (both P < 0.05). Grade + 2 was the most frequent in both sexes. We detected grade 0 in 27.1% of men and 22.1% of women in the control group, with no significant difference in the frequencies of different grades between sexes (P > 0.05). We observed significant differences between grades with respect to the frequency of ocular surface lesions (P < 0.001). Pairwise analysis revealed a significantly higher frequency of ocular surface lesions in asymptomatic individuals with grade 0 and all four other grades (all P < 0.001). However, the frequency of ocular surface lesions was comparable between sexes (P > 0.05). Of the 40 symptomatic individuals, 28 (70%), 5 (12.5%), 4 (10%), and 3 (7.5%) had grade 0, + 1, -1, and -2, respectively. The number of symptomatic patients was higher in grade 0 (n = 28) than in other grades (grade + 1, -1, and -2: n = 12 patients), and these individuals had a higher frequency of ocular surface lesions (n = 38 lesions) than others (grade + 1, -1, and -2: 7 lesions). Conclusions: Using a simple, practical grading scale for Bell's phenomenon that includes inverse Bell's phenomenon, we observed that inverse Bell's phenomenon is a reflex that may be present in healthy individuals and could have a protective effect on the eye, although not to such a degree as a strong Bell's phenomenon. Our observations imply that bilateral conjunctival calcifications/Vogt's limbal girdle may be associated with grades 0 and + 1 Bell's phenomenon. Further large-scale studies are needed to determine the frequency of Bell's phenomenon in the general population using this innovative, simple, practical grading scale, and to identify the protective or injurious effect of each grade on the ocular surface.