Lacrimal Canaliculitis: A Major Review.

Lacrimal canaliculitis is an inflammation of the proximal lacrimal drainage system. It classically presents with symptoms of redness, mucopurulent discharge, medial canthal swelling, epiphora, and pouting punctum. Despite having classical clinical characteristics it is frequently misdiagnosed. The cause can be primarily due to various infectious agents or secondary mostly due to the use of punctal plugs. There are no universally accepted guidelines for the management of canaliculitis but different medical and surgical options have been employed with varying success rates and it is notorious for recurrences and failure to therapy. The present review summarizes the existing literature on lacrimal canaliculitis published over the past 15 years to provide an overview of this uncommon condition. A total of 100 articles published in the literature were anlaysed during this period. The mean age at diagnosis was 57.09 ± 16.91 years with a female preponderance. Misdiagnosis was common with many patients misdiagnosed as conjunctivitis and dacryocystitis. Primary canaliculitis was found to be more frequent than secondary with inferior canaliculus involved more commonly than the superior. Staphylococcus, Streptococcus, and Actinomyces were the most common microbes isolated. Surgical management was employed in 74.25% of cases while medical management was done in 20.82% of cases. The review presents an insight into the complexities of canaliculitis, its diagnosis, and management which will further help to improve the understanding of this uncommon infection of the lacrimal system.

Characterization of AICAR transformylase/IMP cyclohydrolase (ATIC) bifunctional enzyme from Candidatus Liberibacer asiaticus.

The bifunctional enzyme, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase (ATIC) is involved in catalyzing penultimate and final steps of purine de novo biosynthetic pathway crucial for the survival of organisms. The present study reports the characterization of ATIC from Candidatus Liberibacer asiaticus (CLasATIC) along with the identification of potential inhibitor molecules and evaluation of cell proliferative activity. CLasATIC showed both the AICAR Transformylase (AICAR TFase) activity for substrates, 10-f-THF (Km, 146.6 µM and Vmax, 0.95 µmol/min/mg) and AICAR (Km, 34.81 µM and Vmax, 0.56 µmol/min/mg) and IMP cyclohydrolase (IMPCHase) activitiy (Km, 1.81 µM and Vmax, 2.87 µmol/min/mg). The optimum pH and temperature were also identified for the enzyme activity. In-silico study has been conducted to identify potential inhibitor molecules through virtual screening and MD simulations. Out of many compounds, HNBSA, diosbulbin A and lepidine D emerged as lead compounds, exhibiting higher binding energy and stability for CLasATIC than AICAR. ITC study reports higher binding affinities for HNBSA and diosbulbin A (Kd, 12.3 µM and 34.2 µM, respectively) compared to AICAR (Kd, 83.4 µM). Likewise, DSC studies showed enhanced thermal stability for CLasATIC in the presence of inhibitors. CD and Fluorescence studies revealed significant conformational changes in CLasATIC upon binding of the inhibitors. CLasATIC demonstrated potent cell proliferative, wound healing and ROS scavenging properties evaluated by cell-based bioassays using CHO cells. This study highlights CLasATIC as a promising drug target with potential inhibitors for managing CLas and its unique cell protective, wound-healing properties for future biotechnological applications.

Canaliculocoele: A Case Series and Review of Literature.

AIM: To report a case series on canaliculocoele and to review the existing literature. METHODS AND MATERIALS: A retrospective analysis of the case records of all patients diagnosed with canaliculocoele between January 1st, 2018, and December 31st, 2019, was conducted. Only histopathologically proven cases of canaliculocoele with a minimum follow-up of 6 weeks were included. RESULTS: Five cases of canaliculocoele that presented over 2 years were included. The mean age was 58.8 ± 9.63 years, with a female preponderance. The mean duration of symptoms was 22.2 ± 22.71 months. All patients had medial cystic swelling, either at the upper or lower lid. Four patients had gross stenosis of the punctum, while the punctum was absent in one patient. Ultrasound biomicroscopy showed canalicular cystic distension with intra-lesional hyper-reflective echoes. All patients were managed with a complete cystectomy, except for one where a marsupialization was done. Adjunctive mini-Monoka intubation was done in two patients. The histopathological diagnosis of all cases was consistent with canaliculocoele. The mean follow-up was 3.82 ± 2.77 months. CONCLUSION: Canaliculocoele is mostly unilateral and seen in middle-aged women. A good clinical evaluation supported by diagnostic imaging along with an affirmative histopathology can confirm the diagnosis.

Eccrine spiradenoma of eyelid - a rare tumor at an unusual location with literature review.

Eccrine spiradenoma is a rare sweat gland tumor and usually presents as a solitary, painful nodule. A solitary spiradenoma involving the eyelid is quite rare. A 39-year-old Indian female presented with a gradually increasing, painless, nodular upper eyelid mass for the past 4 years. On examination, a non-tender approximately 4 × 3 mm cystic mass was noted, which was not adherent to underlying structures. The mass was excised in toto, and the histopathological examination was suggestive of eccrine spiradenoma with a low Ki-67 index. The patient was doing well without any signs of recurrence at 2 months of follow-up.

Characterization of haloacid dehalogenase superfamily acid phosphatase from Staphylococcus lugdunensis.

The haloacid dehalogenase superfamily implicated in bacterial pathogenesis comprises different enzymes having roles in many metabolic pathways. Staphylococcus lugdunensis, a Gram-positive bacterium, is an opportunistic human pathogen causing infections in the central nervous system, urinary tract, bones, peritoneum, systemic conditions and cutaneous infection. The haloacid dehalogenase superfamily proteins play a significant role in the pathogenicity of certain bacteria, facilitating invasion, survival, and proliferation within host cells. The genome of S. lugdunensis encodes more than ten proteins belonging to this superfamily. However, none of them have been characterized. The present work reports the characterization of one of the haloacid dehalogenase superfamily proteins (SLHAD1) from Staphylococcus lugdunensis. The functional analysis revealed that SLHAD1 is a metal-dependent acid phosphatase, which catalyzes the dephosphorylation of phosphorylated metabolites of cellular pathways, including glycolysis, gluconeogenesis, nucleotides, and thiamine metabolism. Based on the substrate specificity and genomic analysis, the physiological function of SLHAD1 in thiamine metabolism has been tentatively assigned. The crystal structure of SLHAD1, lacking 49 residues at the C-terminal, was determined at 1.7 Å resolution with a homodimer in the asymmetric unit. It was observed that SLHAD1 exhibited time-dependent cleavage at a specific point, occurring through a self-initiated process. A combination of bioinformatics, biochemical, biophysical, and structural studies explored unique features of SLHAD1. Overall, the study revealed a detailed characterization of a critical enzyme of the human pathogen Staphylococcus lugdunensis, associated with several life-threatening infections.

Neoadjuvant Chemotherapy in a Case of Nonresectable Papillary Squamous Cell Carcinoma of the Palpebral Conjunctiva.

The role of neoadjuvant chemotherapy (NACT) in eyelid and orbital malignancies is not well defined. It has been tried with good success in cases of eyelid sebaceous gland carcinoma but there is very limited literature on its role in cases of ocular surface squamous neoplasia. A 54-year-old man presented with gradually increasing swelling of the right upper eyelid for the past 2 years. On examination, a large friable papillary mass was found covering the entire conjunctival surface (T3N0M0). Incisional biopsy from the mass was suggestive of papillary squamous cell carcinoma. There was no lymph node or distant metastasis as confirmed by whole-body positron emission tomography-CT scan. A trial of NACT (3 cycles of paclitaxel and cisplatin) was given and the mass shrunk in size considerably making it amenable to surgical resection. The conjunctival surface healed completely and there was no recurrence at 1 year of follow up. NACT can be tried in unresectable large ocular surface neoplasia to make the tumor more amenable to surgical resection.

Clinical spectrum and clinicopathological correlation of pediatric orbital tumors: 20 years' experience from a tertiary eye care center.

PURPOSE: To study the epidemiological profile of various pediatric orbital tumors and determine their clinicopathological correlation over 20 years. METHODS: A retrospective analysis of all pediatric patients with orbital tumors from the medical records between 1995 and 2015 was done. Tumors were categorized based on their cellular origin. Demographic details, clinical and histopathological diagnoses, frequency, and clinicopathological correlation were studied. RESULTS: A total of 265 pediatric patients with orbital tumors were analyzed, of which 145 (54.7%) patients were males and 120 (45.3%) were females. The mean age was 7 years (median: 6 years; range: 10 days-16 years). The distribution of lesions in each group was as follows: vasculogenic, 76 (28.7%); lipogenic and myxoid, 66 (25%); myogenic, 31 (11.7%); optic nerve and meningeal, 22 (8.3%); lymphoid and lymphoproliferative, 18 (6.8%); secondary orbital tumors, 14 (5.2%); histiocytic, 9 (3.4%); miscellaneous, 9 (3.4%), lacrimal gland, 8 (3%); mesenchymal with neural differentiation, 6 (2%); osseous, 4 (1.5%), and fibrocystic, 2 (0.8%). The most common benign and malignant pediatric orbital tumors were dermoid cysts (65, 24.5%) and rhabdomyosarcoma (31, 11.7%). A statistically significant ( P < 0.0001) clinicopathological correlation was observed in 208 (83.2%) out of 250 biopsy-proven cases. CONCLUSION: Pediatric orbital neoplasms include a broad spectrum of benign and malignant lesions. Vasculogenic tumors constitute the majority of them, followed by lipogenic and myxoid tumors. A thorough knowledge of the incidence, clinical profile, imaging features, and histopathology of specific orbital tumors aids in accurate diagnosis and their successful management.

A rare case of lacrimal sac dirofilariasis confirmed by polymerase chain reaction.

A 69-year-old female presented with complaints of persistent watering in the left eye for the past 8 years. She underwent a left external dacryocystorhinostomy (DCR) 8 years ago. On examination, left lacrimal passage irrigation showed regurgitation of fluid from opposite punctum. She underwent a revision external DCR with bicanalicular intubation and a portion of fibrosed sac was sent for histopathological examination (HPE). HPE showed a Microfilarial worm with surrounding granulomatous inflammation. Polymerase chain reaction (PCR) on the DNA extracted from the specimen identified the species to be Dirofilaria repens. Dirofilariasis is an accidental zoonotic infection in humans. Due to its migration, the worm can affect ocular and periocular structures. There are two case reports of perilacrimal dirofilariasis. This is the first case to report a filarial worm in the lacrimal sac causing chronic inflammation which probably led to failure of DCR. Treatment of choice is the complete eradication of the worm. PCR aids in the identification of species.

Congenital orbital fibrosis: report of two cases and review of literature.

A 7-year-old male child presented with complaints of lagophthalmos and lid retraction of the right eye since birth. Magnetic resonance imaging (MRI) showed diffuse thickening of right superior rectus and levator-palpebrae complex along with a hypointense, irregular, and ill-defined lesion in the adjoining fat abutting the lacrimal gland. Biopsy from the lesion showed diffuse orbital fibrosis. Another 3-year-old female child presented with complaints of her right eye appearing smaller and inability to move the right eye freely since birth. MRI showed thickening of right superior and medial recti with diffuse retrobulbar hypointense fibrotic strands. The findings were suggestive of orbital fibrosis. Congenital orbital fibrosis is an extremely rare orbital pathology with very few cases described in the literature. The most common clinical features are motility restriction, restrictive strabismus, upper lid retraction, enophthalmos, and proptosis. The diagnosis can be made on imaging but requires biopsy for confirmation. Management is mostly conservative in the form of refractive and amblyopia therapy.

A rare case of intramuscular orbital amyloidosis presenting as progressive esotropia in an adult.

Orbital amyloidosis is an uncommon entity. Lacrimal gland, orbital soft tissue and extraocular muscles are the usual sites of involvement. Deposition of amyloid in the extraocular muscle can be either isolated or associated with systemic amyloidosis. We describe a case of a 43-year-old male with isolated amyloid infiltration of the right lateral rectus muscle presenting as a progressive esotropia. The case was initially misdiagnosed as lateral rectus palsy and myositis due to non-specific radiological features of the entity. The diagnosis was confirmed by a biopsy. Intramuscular Botulinum toxin injection, was administered to the right medial rectus to alleviate diplopia temporarily, and strabismus surgery was planned at a later stage. Amyloid deposition is a rare cause of extraocular muscle enlargement. Histopathology is confirmatory. Screening for systemic amyloidosis is mandatory in all cases.

In silico identification of potential phytochemical inhibitors targeting farnesyl diphosphate synthase of cotton bollworm (Helicoverpa armigera).

Helicoverpa armigera (Ha), a polyphagous pest, causes significant damage to several crop plants, including cotton. The control of this cosmopolitan pest is largely challenging due to the development of resistance to existing management practices. The Juvenile Hormone (JH) plays a pivotal role in the life cycle of insects by regulating their morphogenetic and gonadotropic development. Hence, enzymes involved in JH biosynthesis are an attractive target for the development of selective insecticides. Farnesyl diphosphate synthase (FPPS), a member protein of (E)-prenyl-transferases, is one of the most crucial enzymes in the biosynthetic pathway of JHs. It catalyzes the condensation of isopentenyl diphosphate (IPP) with dimethylallyl diphosphate (DMAPP), forming farnesyl diphosphate (FPP), a precursor of JH. The study was designed to identify an effective small inhibitory molecule that could inhibit the activity of Helicoverpa armigera - FPPS (HaFPPS) for an effective pest control intervention. Therefore, a 3D model of FPPS protein was generated using homology modeling. The FooDB database library of small molecules was selected for virtual screening, following which binding affinities were evaluated using docking studies. Three top-scored molecules were analyzed for various pharmacophore properties. Further, molecular dynamics (MD) simulation analysis showed that the identified molecules (mitraphylline-ZINC1607834, chlorogenic acid-ZINC2138728 and llagate-ZINC3872446) had a reasonably acceptable binding affinity for HaFPPS and resulted in the formation of a stable HaFPPS-inhibitor(s) complex. The identified phytochemical molecules may be used as potent inhibitors of HaFPPS thus, paving the way for further developing environment-friendly insect growth regulator(s). Communicated by Ramaswamy H. Sarma.