Clinical and histopathological factors for recurrence and metastasis in lacrimal gland adenoid cystic carcinoma in Chinese patients.

PURPOSE: To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). METHODS: Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. RESULTS: At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). CONCLUSIONS: For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

Design of a new 3D printed all-in-one magnetic smartphone adapter for fundus and anterior segment imaging.

PURPOSE: To describe and validate a 3D-printed adapter tool which could be used with either a slit lamp or a condensing lens, interchangeable between devices through magnetic fastening, in order to provide physicians a quick, easy and effective method of obtaining clinical photos. MATERIALS AND METHODS: Three specialists, with at least 4-year experience in ophthalmology, gave a rate of image quality obtained by our device and the diagnostic confidence grade. The 3 specialists conducted each 13 or 14 examinations with the smartphone and magnetic adapter. At the end of evaluation, they rated with the Likert scale the ease of use of the device in obtaining clinical images of the anterior segment and ocular fundus respectively. RESULTS: Data of quality perception and confidence demonstrated high values not dissimilar to the "de visu" eye examination. Moreover the instrument we designed turned out to be very user friendly. CONCLUSION: Our adapter coupled with a modern smartphone was able to obtain 4k images and videos of anterior segment, central and peripheral fundus, in an easy and inexpensive way.

The etiology, diagnostics, and treatment of the spasm of the near reflex - a narrative review.

Physiological adaptation of the eye to the visual perception of near objects consists of the "near triad": convergence, accommodation, and pupil miosis. Normally, these tend to revert when one stops fixating on a near object. Spasm of the near reflex (SNR) is a pathological phenomenon, which manifests itself by the persistence of the above-mentioned adjustments, which prevents the eye from returning to its relaxed state. In this narrative review, we aim to summarize the etiology, diagnostics, treatment, and prevention of SNR. The literature review was performed by searching online databases. The clinical presentation of SNR is diverse; it presents as isolated accommodative spasm more frequently than impairment of all three components of the near triad. Patients usually present with fluctuations in visual acuity, blurred vision, diplopia, and asthenopia. The etiology is not fully understood. Potential causes include neuroanatomic, organic, and psychogenic disorders. The diagnosis is clinical, based on the constellation of symptoms and assessment of the near triad. The diagnostic golden standard is a cycloplegic examination of refraction, preferably using cyclopentolate hydrochloride (1%, 0.5%, or 0.1% solution). The first-line treatment requires the administration of a cycloplegic drug in combination with plus lenses, flipper lenses, optical fogging, or miotics. For secondary cases, causal treatment should be implemented. Prevention of SNR should be based on eliminating modifiable risk factors. We propose including screening for SNR symptoms in every ophthalmic examination, especially among patients with psychogenic or neural disorders, after brain trauma, or young adults spending much time in front of computer screens.

Medication-associated orbital inflammation: A systematic review.

We performed a comprehensive systematic review to identify medication-associated orbital inflammation and to characterize its clinico-radiological features. We reviewed English-language articles describing medication-associated orbital inflammation (i.e., orbital myositis, dacryoadenitis and orbital fat) published to June, 2023. Isolated inflammation of the intraocular structures or globe alone (i.e. uveitis, scleritis, optic neuritis and perineuritis) were excluded. In medication-associated orbital inflammation, the extraocular muscles are preferentially affected, occurring in isolation or in combination with other orbital and/or intraocular structures. Clinico-radiological manifestations may be non-specific; however, certain medications may be distinguished according to the presence of systemic prodrome, laterality, associated intraocular inflammation, and predisposition to involve certain orbital structures. Rapid identification, discontinuation of the provoking medication, and systemic corticosteroid therapy (if appropriate) typically achieves a favorable visual prognosis. As new medications become adopted by clinicians, rare adverse effects will be further delineated.Medication-associated orbital inflammation is an important diagnostic consideration in orbital inflammatory disease. A careful medication history and clinical assessment may be revealing, permitting timely discontinuation of the offending agent and initiation of appropriate management.

Euthyroid graves' ophthalmopathy in a Chinese population: A cross-sectional follow-up study.

OBJECTIVES: A subtype of patients with thyroid eye disease (TED) were found to be euthyroid without prior thyroid dysfunction or treatment, known as Euthyroid Graves' Ophthalmopathy (EGO). We report the prevalence, clinical and serological phenotypes of EGO in a Chinese population. METHODS: A cross-sectional follow-up study. Ethnic Chinese TED patients were managed at the Thyroid Eye Clinic(TEC), Prince of Wales Hospital and TEC, the Chinese University of Hong Kong between September 2007 and July 2021. RESULTS: A total of 66 (5%) patients among the 1266 ethnic Han Chinese TED cohort were diagnosed as EGO, and 6 (9%)of them become dysthyroid over an average of 74-month follow-up. EGO patients were associated with a longer duration between onset of the symptoms to our first consultation (P < 0.0001), a higher male-to-female ratio (P = 0.0045) and a higher age of disease onset (P = 0.0092). Family history of thyroid disease was more common in TED patients (P = 0.0216) than in EGO patients. EGO patients were more likely to present unilaterally (P < 0.0001), and they have a larger difference in MRD1 (P < 0.0001), and extraocular motility (P < 0.0001) between the 2 eyes when compared to the TED patients. Notably, the extraocular motility restriction of the worst eye was more affected in EGO patients (P = 0.0113). The percentages of patients who received IVMP, ORT and emergency or elective surgeries(decompression or squint operation) between EGO and TED were similar. CONCLUSIONS: Understanding the important clinical phenotypes of EGO may help the clinician to make the correct diagnosis. Further study to compare EGO and TED is warranted.

Ocular Sarcoidosis.

Sarcoidosis frequently affects the eye and can do so in many different ways. Sarcoidosis causing uveitis can have distinctive features that facilitate identifying sarcoidosis as the cause of the uveitis. Progress is being made in elucidating ocular sarcoidosis, as for example, by transcriptomics, genetics, therapy, and imaging.

Sclerotherapy with intralesional bleomycin injection under guidance of multi-slice CT for retrobulbar orbital low-flow vascular lesions-single-center experience.

OBJECTIVE: This study investigated the safety and efficacy of sclerotherapy with intralesional bleomycin injection (IBI) for retrobulbar orbital low-flow vascular lesions under multi-slice computed tomography (CT) guidance. METHODS: Between January 2010 and September 2021, consecutive patients with retrobulbar orbital low-flow vascular lesions who underwent CT-guided IBI at a tertiary centre in Taiwan were enrolled. Their medical records and imaging data were retrospectively collected. RESULTS: This study enrolled 13 patients (7 male and 6 female patients; age range: 1-57 years; mean age: 25.9 years) with lymphatic malformation (LM, n = 4), venolymphatic malformation (n = 1), and venous malformation (VM, n = 8). The overall radiological response rate was 76.9% (10 of 13); the radiological response rate was 75.0% in the VM group (6 of 8) and 75.0% in the LM group (3 of 4). Moreover, 3 patients (23.1%) had minor complications and 1 (7.7%) had a major complication. The mean clinical and radiological follow-up was 8.3 months and no recurrence or progression was reported. CONCLUSION: CT-guided IBI is an effective and relatively safe minimally invasive treatment for retrobulbar orbital low-flow vascular lesions, with an overall radiological response rate of 76.9% in a mean of 1.5 sessions and a low complication rate. ADVANCES IN KNOWLEDGE: CT-guided sclerotherapy with IBI is a relatively safe, effective, and feasible alternative treatment option for retrobulbar orbital low-flow vascular lesions.

OCT-angiography in optic disk pit after inverted ILM flap: A case report.

BACKGROUND: To describe OCT-angiography features in a case of an optic disk pit (ODP) which underwent a pars plana vitrectomy with inverted ILM flap for macular detachment. CASE PRESENTATION: A 12 years old child with an ODP responsible for a macular detachment underwent 23G vitrectomy in the subacute phase of the disease with an inverted ILM flap used as a plug over the lateral dehiscence of the pit. Among the various retinal imaging examinations performed in the post-operative period, the OCT-angiography showed very interesting features characterized by a capillary drop-out in correspondence of the superficial and deep capillary plexus, a fine texture of the choroid capillary layer and star-shaped folds in correspondence of both the outer retina and the choroid capillary layer. OCT-A performed 24 months after surgery showed a normalization of the macular perfusion which correlated with a full recovery of the visual acuity of the young child. CONCLUSIONS: OCT-A is an useful tool to monitor the subretinal fluid reabsorption after ILM inverted flap surgery for ODP-maculopathy and correlates with visual function. OCT-A may be useful in the follow-up of this rare condition as well as its response to therapeutic strategies.

Orbital mucosa-associated lymphoid tissue (MALT) lymphoma as the initial presentation in patients with hepatitis C virus infection

ABSTRACT Hepatitis C virus infection may be implicated in 12.7% of ocular adnexal marginal zone lymphomas. We present the first case of an orbital-systemic mucosa-associated lymphoid tissue lymphoma that responded to hepatitis C virus medical treatment. A 62-year-old male with a right-sided orbital mass was diagnosed with stage IIA orbital marginal zone lymphoma in addition to hepatitis C virus infection based on clinical, imaging, laboratory, and histological examinations. The systemic and orbital responses were achieved 1 year after undergoing hepatitis C virus treatment with glecaprevir/pibrentasvir. The association between the hepatitis C virus infection and orbital-systemic mucosa-associated lymphoid tissue lymphoma is relevant. Accordingly, patients with orbital mucosa-associated lymphoid tissue lymphoma should be assessed for hepatitis C virus seroreactivity for therapeutic and prognostic purposes.

Guidelines for the operation of imaging equipment in orbital diseases(2024) / 国际眼科杂志(Guoji Yanke Zazhi)

Orbital disorders include conditions originating from the orbital bones, surrounding tissues, and post-orbital septum. They also include systemic ailments affecting the orbit. Different clinical symptoms make up the complex range of orbital disorders. Because these disorders mostly impact the orbital area instead of the intraocular compartment, there is little diagnostic usefulness for typical ophthalmic visual tests. As such, the primary instruments for diagnosing and evaluating orbital illnesses have become ophthalmic imaging modalities, including ocular ultrasonography(B-scan), computed tomography(CT), and magnetic resonance imaging(MRI). One way to improve the precision and promptness of diagnosing orbital diseases is to standardize the functioning of widely used imaging equipment and define the radiological features of orbital abnormalities. Such programs are crucial for the care of patients with orbital disorders since they considerably reduce the number of misdiagnoses and missed diagnoses in these individuals. The underlying concepts, operational techniques, and normal and pathological imaging findings associated with common diagnostic tools for orbital illnesses are all thoroughly reviewed in this guideline. The objective is to improve primary healthcare settings' diagnostic competence in the field of orbital pathology and to standardize procedures for diagnosing orbital disorders.

Research progress of finite element method in the biomechanics of the orbit / 国际眼科杂志(Guoji Yanke Zazhi)

The finite element method(FEM)is a widely employed mathematical technique in mechanical research that divides an object into discrete and interacting finite elements. Medically, finite element analysis(FEA)enables the simulation of biomechanical experiments that are challenging to conduct. Orbital surgery poses significant challenges to ophthalmologists due to its inherent difficulty and steep learning curve. FEM enables the simulation and analysis of the mechanical properties of orbital tissue, offering a novel approach for diagnosing and treating orbital-related diseases. With technological advancements, FEM has significantly matured in the diagnosis and treatment of orbital diseases, becoming a popular area of research in orbital biomechanics. This paper reviewed the latest advancements in orbital FEM, encompassing the development of orbital FEA models, simulation of orbital structure, and its application in orbital-related diseases. Additionally, the limitations of FEM and future research directions are also discussed. As a digital tool for auxiliary diagnosis and treatment, orbital FEA will progressively unlock its potential for diagnosing and treating orbital diseases alongside technological advancements.

Isolated bilateral orbital and paranasal Rosai-Dorfman disease affecting two brothers: a case report and a systematic literature review.

A systematic literature review revealed 88 Rosai-Dorfman Disease (RDD) cases affecting the orbit. We present a review of the literature on orbital RDD in addition to two brothers with isolated bilateral extra-nodal orbital RDD cases associated with G-6PD deficiency. The disease manifested as asymmetric extensive orbital and paranasal sinus infiltration, with orbital bone destruction. Orbital mass debulking and steroids improved the condition in both patients. This is the most extensive case series of orbital RDD reported, including clinical manifestation, imaging, pathologic results, management, and outcome. Vigilant follow-up is essential to monitor for potential malignant transformation, systemic manifestations, potential vision loss, or life-threatening recurrences.

A Rare Case Report of Periorbital Pseudolymphoma.

Pseudolymphoma (PSL) of the orbit is a benign lymphoid hyperplasia (LH). It is a rare disease with an extensive range of known causative agents. LH is further classified into "reactive" (RLH) and "atypical" (ALH) types. It clinically presents as a single or a few plaques and/or nodular lesions, particularly on the head, neck, and upper trunk. It must be differentiated from orbital malignant lymphoma. In this report, we present a case of a 58-year-old Pakistani female with an asymptomatic recurrent right periorbital swelling for three years. It was clinically diagnosed as an angiotensin-converting enzyme (ACE) inhibitor-induced angioedema as it responded to stopping the ACE inhibitor; however, after four months, the patient again started to develop right periorbital swelling. An incisional biopsy revealed perivascular and periadnexal infiltration of lymphocytes, plasma cells, and a few neutrophils along with pigmentary incontinence. The formation of multiple lymphoid follicles and infiltration by monomorphic lymphoid cells in deeper skeletal muscle fibers were also observed. Immunohistochemistry (IHC) showed polyclonality and low Ki-67 labeling (20%), corresponding to periorbital RLH. Our objective in this study is to highlight the importance of considering PSL as a differential diagnosis in periorbital swelling. We also suggest that recurrent angioedema may lead to PSL.

Doxycycline sclerotherapy in patients with periorbital lymphatic malformation: A case series and literature review.

PURPOSE: To describe and report the outcomes of doxycycline sclerotherapy in patients with periorbital lymphatic malformations(LMs). BASIC PROCEDURES: A retrospective review of consecutive patients diagnosed with periorbital LMs and who received doxycycline sclerotherapy at Hong Kong Eye Hospital and Queen Elizabeth Hospital, Hong Kong between January 2016 and June 2022. Doxycycline was prepared with a concentration of 100 mg diluted in 10 mL water for injection. A 23-gauge needle aiming at the center of the macrocyst was used to aspirate fluid from the lesion; this was then followed by an intralesional injection of 0.5 to 2 ml of doxycycline depending on the size of the cavity. MAIN FINDINGS: A total of eight patients(six females) were included in this study. All of them received doxycycline sclerotherapy for periorbital LMs(five extraconal, three intraconal). The median age for receiving sclerotherapy was 29 years old. Seven patients had macrocystic LMs, and one had mixed macro- and microcystic LM. Two of the LMs had venous components radiologically. The average number of sclerotherapy treatment in one patient was 1.4 ± 0.7times. Seven of the eight patients had excellent response radiologically or clinically. One patient showed a satisfactory response after three cycles of sclerotherapy. No recurrence was experienced at median follow-up of 14 months. None of the patients experienced visual threatening or systemic complication. PRINCIPLE CONCLUSIONS: Our preliminary experience with doxycycline sclerotherapy has shown encouraging results for the treatment of macrocystic or mixed-type periorbital LMs, with a favourable safety profile. Further clinical trials with longer follow-ups are warranted on this topic.

Long term follow-up of congenital infantile fibrosarcoma of the orbital region.

We present the long-term follow-up of a case of periorbital congenital infantile fibrosarcoma (CIFS) treated with chemotherapy and surgery. The tumor was detected on a routine prenatal ultrasound at 30 weeks of gestation and diagnosed via an orbital biopsy day 9 postnatal age. The patient underwent chemotherapy and surgical debulking within the first 3 months of life and has maintained complete tumor remission for 7 years. The case highlights that early recognition and prompt treatment of periorbital CIFS can lead to complete long-term remission of this uncommon malignancy.

Post-COVID simultaneous onset of Graves' disease and ocular myasthenia gravis in a patient with a complex ocular motility impairment.

A 74-years-old man experienced severe diplopia one month after recovery from an uncomplicated SARS-CoV-2 infection. Neurological examination was normal whereas ophthalmological examination showed bilateral exophthalmos with a complex ocular motility disorder characterized by a pseudo-internuclear ophthalmoplegia after fatigue associated to impairment of elevation and infraduction. Antibodies against TSH and acetylcholine receptors were positive; subsequent hormonal tests, ultrasonography of thyroid gland, single fiber electromyography and orbit MRI confirmed the diagnosis of concomitant Graves Disease (GD) and Myasthenia Gravis (MG). The coexistence between MG and GD is not rare but simultaneous onset after viral infection is very unsual. The complex ocular disorder simulated a deficit of the oculomotor nerve nuclei, and on clinical examination it posed some problems in the diagnosis. We suggest that recent SARS-COV-2 infection may have triggered a complex autoimmune response.

Proptosis secondary to bilateral extraocular muscle enlargement in Noonan syndrome with hypertrophic cardiomyopathy: A case report.

PURPOSE: To report and investigate proptosis in a young girl with Noonan syndrome. METHODS: Observational case report. RESULTS: A 16-year-old girl affected by Noonan syndrome underwent a complete ophthalmological examination showing bilateral proptosis with hypofunction of lateral rectus and superior oblique muscles. Visual acuity, color discrimination and fundus examination were unremarkable. The orbital MRI showed bilateral proptosis and symmetrical enlargement of extraocular muscles, with bellies thickening and tendon sparing. The young patient also complained restrictive hypertrophic cardiomyopathy. CONCLUSIONS: Proptosis is an uncommon ocular manifestation of Noonan syndrome and its pathophysiology has never been clarified. The MRI evidence of extraocular muscles enlargement associated with hypertrophic cardiomyopathy, led us to hypothesize a common altered pathway beneath these features, more specifically the MAP kinase pathway, since extraocular and cardiac muscles share a mesenchymal embryological origin.

Ocular manifestations of COVID-19 in the pediatric age group.

The coronavirus disease 2019 (COVID-19) is now known to be associated with several ocular manifestations. The literature thoroughly discussed those that affect adults, with a lesser focus in the pediatric age group. We aim to outline the various pediatric ocular manifestations described in the literature. The manifestations may be divided into isolated events attributed to COVID-19 or occurring in the new multisystem inflammatory syndrome in children (MIS-C), a novel entity associated by COVID-19 infection. Ocular manifestations have virtually affected all ages. They manifested in neonates, infants, children, and adolescents. Episcleritis, conjunctivitis, optic neuritis, cranial nerve palsies, retinal vein occlusion, retinal vasculitis, retinal changes, orbital myositis, orbital cellulitis were reported in the literature with this emerging viral illness. Conjunctivitis was the most common ocular manifestation in MIS-C in nearly half of the patients. Other ocular manifestations in MIS-C were anterior uveitis, corneal epitheliopathy, optic neuritis, idiopathic intracranial hypertension, and retinitis. The clinical outcome was favorable, and children regain their visual ability with minimal or no deficits in most of the cases. Further follow-up may be warranted to better understand the long-term effects and visual prognosis.

Somatic GJA4 gain-of-function mutation in orbital cavernous venous malformations.

Orbital cavernous venous malformation (OCVM) is a sporadic vascular anomaly of uncertain etiology characterized by abnormally dilated vascular channels. Here, we identify a somatic missense mutation, c.121G > T (p.Gly41Cys) in GJA4, which encodes a transmembrane protein that is a component of gap junctions and hemichannels in the vascular system, in OCVM tissues from 25/26 (96.2%) individuals with OCVM. GJA4 expression was detected in OCVM tissue including endothelial cells and the stroma, through immunohistochemistry. Within OCVM tissue, the mutation allele frequency was higher in endothelial cell-enriched fractions obtained using magnetic-activated cell sorting. Whole-cell voltage clamp analysis in Xenopus oocytes revealed that GJA4 c.121G > T (p.Gly41Cys) is a gain-of-function mutation that leads to the formation of a hyperactive hemichannel. Overexpression of the mutant protein in human umbilical vein endothelial cells led to a loss of cellular integrity, which was rescued by carbenoxolone, a non-specific gap junction/hemichannel inhibitor. Our data suggest that GJA4 c.121G > T (p.Gly41Cys) is a potential driver gene mutation for OCVM. We propose that hyperactive hemichannel plays a role in the development of this vascular phenotype.

Analysis of clinical histopathological composition of 699 cases with orbital tumors and tumor-like lesions / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the clinical and histopathological composition of orbital tumors and tumor-like lesions.METHODS: Retrospective case-series study. The clinical histopathological data of 699 cases(707 eyes)with orbital tumor and tumor-like lesions who treated in the orbital disease and ophthalmic plastic department of Tianjin Eye Hospital between January 2010 and December 2020 were collected. All the pathology diagnosis results were divided into three categories which were benign tumor, borderline tumor and malignant tumor according to the eighth edition of the American Joint Committee on Cancer staging system and the 2018 World Health Organization Classification of tumors of the eye. All cases were divided into four groups according to age, including 0～17 years old, 18～39 years old, 40～59 years old, 60 years and above. The histological composition of each group was analyzed.RESULTS: Among the 699 cases(707 eyes), 311 patients(316 eyes)were male and 388 patients(391 eyes)were female. The patient's age at diagnosis ranged from 1 to 84 years(mean 39.9±2.2)years. The right orbit was involved in 307 patients, the left orbit in 384 patients, and 8 patients in bilateral orbit. There were 598 patients(604 eyes, 85.6%)with benign tumor and tumor-like lesions, 7 patients(7 eyes, 1.0%)with borderline tumor, and 94 patients(96 eyes, 13.4%)with malignant tumors. The top 5 benign tumor and tumor-like lesions were cavernous hemangioma(110 cases, 15.7%), dermoid cysts(96 cases, 13.7%), pleomorphic adenomas(54 cases, 7.7%), inflammatory pseudotumors(38 cases, 5.4%), and schwannomas(29 cases, 4.1%)respectively. The top 5 borderline and malignant tumors were non-Hodgkin lymphomas(42 cases, 41.6%), solitary fibrous tumors(12 cases, 11.9%), adenoid cystic carcinomas(11 cases, 10.9%), metastatic tumor(9 cases, 8.9%), and rhabdomyosarcoma(8 cases, 7.9%), respectively. Among the common orbital benign tumors and tumor-like lesions, cavernous hemangioma and pleomorphic adenoma showed a female predominance. Among the common borderline and malignant tumors, non-Hodgkin lymphoma and mesenchymal chondrosarcoma showed a male predominance. The most common benign and malignant tumors were dermoid cysts, rhabdomyosarcomas respectively in group under 18 years old. And dermoid cysts and solitary fibrous tumors were the most common benign and malignant tumors respectively in patients between 18 and 39 years old. Cavernous hemangioma and non-Hodgkin lymphomas were the most common benign and malignant tumors respectively in patients between 40 and 59 years old. While cavernous hemangioma and non-Hodgkin lymphomas were the most common benign and malignant tumors respectively in cases over 60 years old.CONCLUSION: Most orbital tumors and tumor-like lesions are benign. The most common benign orbital tumor is cavernous hemangioma, followed by dermoid cyst. Non-Hodgkin lymphoma is the most common malignant orbital tumor.