Lacrimal Gland Enlargement Research Articles

Plasma cell type Castleman's disease of lacrimal gland: a case report and literature review

BackgroundOrbital Castleman's disease is a rare benign lymphoproliferative disorder of extranodal origin.Case presentationA 72-year-old man presented with bilateral upper eyelid swelling. Radiology revealed enlarged lacrimal glands in both eyes. Castleman's disease (plasma cell type) was confirmed by histo-immunochemical examinations after excision of the left orbital mass. No extraorbital involvement was found in systemic evaluation. Postoperatively, corticosteroid therapy was given. After 1 year of follow-up, there was no recurrence in the left orbit, and the swelling of the right eyelid was improved.ConclusionsHere, we report a case of orbital Castleman's disease involving the lacrimal gland bilaterally and summarize previously reported cases. For bilateral orbital masses, the possibility of Castleman's disease should be considered. Before the diagnosis, it is necessary to fully distinguish from other diseases such as IgG4-related eye diseases.

Lacrimal gland enlargement in thyroid eye disease.

This study aimed to investigate lacrimal gland (LG) enlargement in thyroid eye disease (TED) patients on magnetic resonance imaging (MRI). A retrospective review was conducted on TED patients who had undergone fat-suppressed contrast-enhanced T1-weighted MRI of the orbits. The lacrimal gland was segmented on OsiriX in consecutive axial and coronal slices to determine its volume. Enlargement was defined as a volume greater than 1100mm3, based on previous normative data. Asymmetric enlargement was defined if one side was enlarged but the contralateral side was not. Clinical data including presentation (active/inactive) and presence or absence of dysthyroid optic neuropathy was evaluated. The study population consisted of 88 orbits from forty-four patients with a mean age of 53 ± 15years, with 29 (65%) being female. Twelve patients (27%) had LG enlargement, with eight (18%) having bilateral enlargement and four (9%) having asymmetric enlargement. There was no significant difference in age (p = 0.17) or sex (p = 0.44) between the LG enlarged and non-enlarged groups. There was also no significant difference in the clinical activity (p = 0.46) or prevalence of dysthyroid optic neuropathy (p = 0.63) between the LG enlarged orbits and non-LG enlarged orbits. Lacrimal gland enlargement may be observed in approximately thirty percent of TED patients, with asymmetric enlargement in approximately ten percent of cases.

IgG4-related disease presented with a neck nodule; a case report

Introduction and importance: Immunoglobulin G4 (IgG4)-related disease is an infrequent systemic condition that affects males more than females. Fatigue, arthralgia, salivary and lacrimal gland enlargement, symptoms of pancreatitis, tubulointerstitial nephritis, and retroperitoneal fibrosis are the frequent manifestations. The spectrum of IgG4-related thyroid disease includes Hashimoto thyroiditis, Graves’ disease, and Riedel thyroiditis. Case presentation: We presented a 49‐year‐old male presented with progressive painless swallowing of the neck for a year without any accompanying symptoms. Conclusion: Expanding goiter is common, but its severity leads to the rare diagnosis of IgG4-related thyroiditis.

Screening of pathologically significant diagnostic biomarkers in tears of thyroid eye disease based on bioinformatic analysis and machine learning.

Lacrimal gland enlargement is a common pathological change in patients with thyroid eye disease (TED). Tear fluid has emerged as a new source of diagnostic biomarkers, but tear-based diagnostic biomarkers for TED with high efficacy are still lacking. We aim to investigate genes associated with TED-associated lacrimal gland lesions. Additionally, we seek to identify potential biomarkers for diagnosing TED in tear fluid. We obtained two expression profiling datasets related to TED lacrimal gland samples from the Gene Expression Omnibus (GEO). Subsequently, we combined the two separate datasets and conducted differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) on the obtained integrated dataset. The genes were employed for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The genes were intersected with the secretory proteins profile to get the potential proteins in the tear fluid. Machine learning techniques were then employed to identify optimal biomarkers and develop a diagnostic nomogram for predicting TED. Finally, gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted on screened hub genes to further elucidate their potential mechanisms in TED. In our analysis of the integrated TED dataset, we identified 2,918 key module genes and 157 differentially expressed genes and finally obtained 84 lacrimal-associated key genes. Enrichment analysis disclosed that these 84 genes primarily pertain to endoplasmic reticulum organization. After intersecting with the secretory proteins, 13 lacrimal gland-associated secretory protein genes (LaSGs) were identified. The results from machine learning indicated the substantial diagnostic value of dyslexia associated gene (KIAA0319) and peroxiredoxin4 (PRDX4) in TED-associated lacrimal gland lesions. The two hub genes were chosen as candidate biomarkers in tear fluid and employed to establish a diagnostic nomogram. Furthermore, single-gene GSEA results and immune cell infiltration analysis unveiled immune dysregulation in the lacrimal gland of TED, with KIAA0319 and PRDX4 showing significant associations with infiltrating immune cells. We uncovered the distinct pathophysiology of TED-associated lacrimal gland enlargement compared to TED-associated orbital adipose tissue enlargement. We have demonstrated the endoplasmic reticulum-related pathways involved in TED-associated lacrimal gland lesions and established a diagnostic nomogram for TED utilizing KIAA0319 and PRDX4 through integrated bioinformatics analysis. This contribution offers novel insights for non-invasive, prospective diagnostic approaches in the context of TED.

Granulomatosis with polyangiitis with lacrimal gland enlargement and pancreatic swelling: case report and literature review.

A 62-year-old man had bilateral eyelid swelling for 4 months. Two months before admission, he developed fatigue and lost 5 kg of bodyweight. Further examination revealed elevated serum C-reactive protein, normal angiotensin-converting enzyme, elevated proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA), and normal IgG4 concentration. Chest X-ray and computed tomography showed no enlarged hilar lymph nodes, but positron emission tomography-computed tomography showed fluorodeoxyglucose accumulation in both lacrimal glands, in lung nodules, and in the pancreas. Tissue biopsies of the lacrimal glands and pulmonary nodules showed granuloma with giant cells, but no IgG4-positive cells or fibrosis. Pancreatic tissue showed no findings of autoimmune pancreatitis. In the 2022 ACR/EULAR classification criteria for granulomatosis with polyangiitis, the total score was 10 points. Final comprehensive diagnosis was granulomatosis with polyangiitis, based on the negative results of differential diseases, such as IgG4-related diseases and sarcoidosis. Prednisolone 60 mg/day was started on day 8, and rituximab 500 mg/body/week on day 12. After beginning treatment, general malaise and lacrimal gland enlargement were resolved, PR3-ANCA and C-reactive protein became negative, and the nodular shadow in the lungs disappeared. This is the first report of granulomatosis with polyangiitis presenting both lacrimal gland and pancreatic lesions.

Differentiation of bacterial orbital cellulitis and diffuse non-specific orbital inflammation on magnetic resonance imaging.

To examine the radiological differences between bacterial orbital cellulitis (OC) and diffuse non-specific orbital inflammation (DNSOI) on magnetic resonance imaging (MRI). Retrospective study of patients with OC and DNSOI with an MRI orbital scan. Localised orbital inflammation (e.g., idiopathic dacryoadenitis and myositis), quiescent orbital inflammation and pre-septal cellulitis were excluded. Thirty-two patients presenting between 2008 and 2023, including twenty-one OC patients (mean age: 42.5 ± 24.9 years old, male: 6), and eleven DNSOI patients (mean age: 52.3 ± 17.8 years old, male: 16). Both OC and DNSOI demonstrate orbital fat contrast-enhancement. However, whilst OC demonstrated a hyperintense T2 signal (P < 0.001), variable signal was observed in DNSOI, with a hypointense T2 signal more suggestive of DNSOI (P = 0.012). When the lacrimal glands were involved, indistinct margins were more likely in OC (P < 0.001), whilst gross enlargement and contrast-enhancement was observed in DNSOI (P = 0.032 and 0.017, respectively). Peripheral contrast-enhancement of the extraocular muscle (EOM) (P = 0.002) was more common in OC, whilst DNSOI demonstrated variable contrast-enhancement throughout the affected EOM (P < 0.001). The presence of contralateral abnormalities, such as lacrimal gland enlargement and EOM involvement, are more suggestive of DNSOI. Several MRI features, beyond overt sinogenic disease, may help to differentiate OC from DNSOI, including the orbital fat signal intensity, EOM and/or lacrimal gland involvement, and contralateral orbital abnormalities. However, these features may not be specific, and thus highlights the ongoing radiological dilemma clinicians are faced when tasked with differentiating between infectious and non-infectious orbital inflammatory disease.

Lacrimal Gland Inflammation as the First Manifestation of Adult-onset Still’s Disease

Abstract Adult-onset Still’s disease (AOSD) is a systemic idiopathic autoinflammatory disorder with rare ocular involvement. Few cases in the literature reported lacrimal gland inflammation as a manifestation of AOSD. Here, we present a case of a 38-year-old man who presented with an isolated unilateral lacrimal gland inflammation, few months later, he developed fever and arthritis and was investigated, diagnosed, and treated by rheumatology as AOSD. Resolution of lacrimal gland enlargement was achieved while on prednisolone and methotrexate. To the best of our knowledge, this is the first case to present with lacrimal gland inflammation as a first manifestation of AOSD.

Unilateral Dacryoadenitis as the First Symptom of Systemic Lupus Erythematous.

This case report focuses on a patient with systemic lupus erythematous whose first symptom was dacryoadenitis. A 42-year-old Asian woman presented with a 3-day history of left periorbital swelling and pain. Gross examination revealed left periorbital swelling with no definite tenderness. Initial computed tomography with contrast showed diffuse enhancement and enlargement of the left lacrimal gland with adjacent fluid collection, indicating periorbital soft tissue swelling. She was diagnosed with left dacryoadenitis and treated with intravenous methylprednisolone (60mg/day) and oral prednisolone (10mg/day). Over the next 6 months, she experienced numerous instances of recurrence, which was shortly responsive to oral and intravenous high-dose steroids. Immunosuppressive therapy was selected, and upon conducting laboratory tests, she was diagnosed with systemic lupus erythematous. Since then, the patient has undergone treatment involving hydroxychloroquine (200mg/day) and azathioprine (50mg/day) with no recurrence.

Lacrimal gland enlargement in inactive thyroid eye disease: a case series and literature review.

This study aimed to evaluate the morphometric and volumetric dimensions of the lacrimal gland in patients with inactive thyroid eye disease and compare them with the values reported in the literature. This case series evaluated consecutive patients with inactive thyroid eye disease treated at a tertiary eye hospital from 2015 to 2020. The patients' baseline demographics and clinical characteristics were obtained. The axial and coronal length, width, and volume of the lacrimal gland were measured on computed tomography scan images, and the results were statistically analyzed. A total of 21 patients (42 orbits) with inactive thyroid eye disease were evaluated. Their mean age was 49.0 ± 14.6 years, and 12 (57.1%) of them were men. The main complaint was dryness, and the majority of the patients had good vision and mild proptosis. The mean axial length and width of the lacrimal gland were 19.3 ± 3.9 mm and 7.5 ± 2.1 mm, respectively; coronal length and width, 20.4 ± 4.5 mm and 7.5 ± 2.1 mm, respectively; and lacrimal gland volume, 0.825 ± 0.326 mm3. Age, sex, or laterality were not found to be determinants of lacrimal gland enlargement. Patients with thyroid eye disease have enlarged lacrimal gland even in the nonactive phase of the disease multifactorial aspects influence the lacrimal gland in thyroid eye disease, making it difficult to establish a clear correlation with predisposing factors. Further studies are warranted to better understand the association between thyroid eye disease and the lacrimal gland.

An Eosinophilic Variant of Orbital Granulomatosis with Polyangiitis with Ocular Motility Disorder

Purpose: To present the case of a patient with localized orbital granulomatosis with polyangiitis (GPA) characterized by a significant ocular motility disorder, increased eosinophilia, and hyper-immunoglobulin E (hyper-IgE).Case Summary: A 61-year-old male, with no previous history of allergy, atopy, asthma, sinonasal disease, respiratory disease, or renal disease, came to our hospital due to a 2-day history of binocular diplopia. His left eye exhibited inward and upward deviation, along with gaze limitation. His vision was 20/20 in both eyes, and the pupillary light reflex and color test were normal. He had severe eyelid swelling and conjunctival injection without tenderness in his left eye, and retinal vessel congestion around the optic nerve, without proptosis. Laboratory tests revealed a positive cytoplasmic antineutrophil cytoplasmic antibody (cANCA), a normal WBC count, elevated eosinophils at 28.3% (2,462/mm&lt;sup&gt;3&lt;/sup&gt;), and high serum levels of IgE (400 KU/L). Magnetic resonance imaging showed an inferolateral orbital mass with an enlarged lacrimal gland and myositis of the extraocular muscles. A biopsy of the lacrimal gland revealed nonspecific chronic inflammation with an eosinophilic infiltrate. The presence of cANCA, in combination with clinical and pathological findings, led to the diagnosis of an eosinophilic variant of localized orbital GPA. This variant was primarily confined to the orbital tissue, marked by elevated eosinophil and IgE levels, and was treated with oral steroids without requiring surgery for the ocular motility disorder.Conclusions: GPA may present as acute strabismus with orbital inflammation, even in the absence of systemic signs. Therefore, it should be considered in the differential diagnosis of unexplained acute orbital syndromes.

Three Blind Moles: Molecular Evolutionary Insights on the Tempo and Mode of Convergent Eye Degeneration in Notoryctes typhlops (Southern Marsupial Mole) and Two Chrysochlorids (Golden Moles).

Golden moles (Chrysochloridae) and marsupial moles (Notoryctidae) are textbook examples of convergent evolution. Both taxa are highly adapted to subterranean lifestyles and have powerful limbs for digging through the soil/sand, ears that are adapted for low-frequency hearing, vestigial eyes that are covered by skin and fur, and the absence of optic nerve connections between the eyes and the brain. The eyes of marsupial moles also lack a lens as well as retinal rods and cones. Two hypotheses have been proposed to account for the greater degeneracy of the eyes of marsupial moles than golden moles. First, marsupial moles may have had more time to adapt to their underground habitat than other moles. Second, the eyes of marsupial moles may have been rapidly and recently vestigialized to (1) reduce the injurious effects of sand getting into the eyes and (2) accommodate the enlargement of lacrimal glands that keep the nasal cavity moist and prevent the entry of sand into the nasal passages during burrowing. Here, we employ molecular evolutionary methods on DNA sequences for 38 eye genes, most of which are eye-specific, to investigate the timing of relaxed selection (=neutral evolution) for different groups of eye-specific genes that serve as proxies for distinct functional components of the eye (rod phototransduction, cone phototransduction, lens/cornea). Our taxon sampling included 12 afrothere species, of which two are golden moles (Amblysomus hottentotus, Chrysochloris asiatica), and 28 marsupial species including two individuals of the southern marsupial mole (Notoryctes typhlops). Most of the sequences were mined from databases, but we also provide new genome data for A. hottentotus and one of the two N. typhlops individuals. Even though the eyes of golden moles are less degenerate than the eyes of marsupial moles, there are more inactivating mutations (e.g., frameshift indels, premature stop codons) in their cone phototransduction and lens/cornea genes than in orthologous genes of the marsupial mole. We estimate that cone phototransduction recovery genes were inactivated first in each group, followed by lens/cornea genes and then cone phototransduction activation genes. All three groups of genes were inactivated earlier in golden moles than in marsupial moles. For the latter, we estimate that lens/cornea genes were inactivated ~17.8 million years ago (MYA) when stem notoryctids were burrowing in the soft soils of Australian rainforests. Selection on phototransduction activation genes was relaxed much later (5.38 MYA), during the early stages of Australia's aridification that produced coastal sand plains and eventually sand dunes. Unlike cone phototransduction activation genes, rod phototransduction activation genes are intact in both golden moles and one of the two individuals of N. typhlops. A second marsupial mole individual has just a single inactivating mutation in one of the rod phototransduction activation genes (PDE6B). One explanation for this result is that some rod phototransduction activation genes are pleiotropic and are expressed in extraocular tissues, possibly in conjunction with sperm thermotaxis.

Histopathological features of asymmetric lacrimal gland enlargement in patients with thyroid eye disease

PurposeLacrimal gland enlargement can be a feature of thyroid eye disease (TED). Unilateral or asymmetric lacrimal gland enlargement is poorly described and may impede diagnosis. We present the histological and clinical findings of four patients with asymmetric lacrimal gland enlargement.MethodsA retrospective case note review was performed for patients over two tertiary orbital clinics (Royal Adelaide Hospital, South Australia and the Sussex Eye Hospital, Brighton, United Kingdom) presenting with an asymmetrical lacrimal gland enlargement with a background of TED that underwent biopsy to exclude alternate diagnoses. Baseline data was collected for each patient and histopathological images and reports were reviewed.ResultsAll four patients were hyperthyroid at time of lacrimal gland biopsy. Biopsy demonstrated nonspecific, lymphoid aggregates, typically of B cell type, with no diagnostic findings to support lymphocyte clonality or IgG4-related disease. One biopsy specimen demonstrated evidence of some fibrosis.ConclusionAsymmetrical lacrimal gland enlargement can occur as part of the TED spectrum but may require biopsy to exclude alternate pathology. Histology demonstrates a non-specific lymphocytic infiltrate.

Ocular Surface Evaluation in Immunoglobulin G4–Related Ophthalmic Disease

To evaluate the functional and structural changes of the meibomian glands and ocular surface in immunoglobulin G4-related ophthalmic disease (IgG4-ROD) patients. Cross-sectional, matched case-control comparison study. This study included 64 patients with biopsy-proven IgG4-ROD (aged 63.4 ± 12.2 years, 39 male) and 64 sex- and age-matched healthy controls. Patients were managed by hospitals covering the publicly funded ophthalmology service in Hong Kong. Outcome measures included anterior segment examination and keratographic and meibographic imagings. A total of 64 worst-affected eyes of the 64 IgG4-ROD patients were analyzed. Corneal fluorescein staining (P=.0187), lid margin telangiectasia (P=.0360), lid-parallel conjunctival folds (P=.0112), papillae (P=.0393), meibomian gland plugging (P=.0001), meibomian gland expressibility (P=.0001), and meibum quality (P=.0001) were more significant in IgG4-ROD patients compared with healthy controls. Both upper and lower meibomian gland dropouts (P=.001 and .0003), and tear meniscus height (P=.0001) were higher in IgG4-ROD patients. Non-invasive tear break-up time (NITBUT) (P=.0166) and Schirmer test results (P=.0243) were lower in IgG4-ROD patients. Upper (r=0.336, P=.0140) meibomian gland dropouts and NITBUT (r=-0.293, P=.0497) were positively and negatively correlated with the IgG4-ROD onset age, respectively. The number of extraocular organ involvement was negatively correlated with the Schirmer test(r=-0.341, P=.0167). Lower NITBUT was found in IgG4-ROD eyes with lacrimal gland enlargement than in IgG4-ROD eyes without lacrimal gland enlargement radiologically (P < .0001). IgG4-ROD patients showed features of both aqueous tear deficiency and evaporative dry eye disease. We recommend ocular surface evaluation to all patients newly diagnosed with IgG4-ROD. Further studies are warranted to clarify the mechanism of IgG4-related dry eye disease.

The Whitnall Barrier: A Technique for the Management of Lacrimal Gland Prolapse.

The Whitnall barrier procedure, a modified Beer and Kompatscher surgical technique to reposition the lacrimal gland, is presented alongside a case series of patients demonstrating excellent aesthetic and functional outcomes. The Whitnall barrier procedure is illustrated procedurally and accompanied by a case series of 20 consecutive patients treated in a single institution by a single surgical team between December of 2016 and February of 2020. Lid contour and function were assessed postoperatively, as was patient satisfaction. Thirty-seven eyes of 20 patients were included. All patients were women, with an average age of 50 years. Fourteen patients underwent surgery for cosmesis, four had inactive thyroid eye disease, and two had lacrimal gland enlargement secondary to dacryoadenitis. The degree of lacrimal gland prolapse was described as mild in two eyes and moderate in 35 eyes. All patients had one or more additional surgical procedures. Mean follow-up duration was 11 months, with complete resolution of lacrimal gland prolapse in 34 eyes. The patient who did not have complete resolution had dacryoadenitis and required ongoing immunosuppressive therapy. Two patients were discharged on topical lubricants: one with thyroid eye disease and one cosmetic patient who underwent upper and lower lid blepharoplasties at the same time. There were no intraoperative complications and no incidences of infection, dehiscence, or damage to the lacrimal gland ductules. The Whitnall barrier technique is a safe and effective surgical procedure to restore the anatomic location of the lacrimal gland. It provides excellent aesthetic and functional outcomes.

Adult-Onset Asthma With Periocular Xanthogranuloma: Clinical-Histological Correlation.

A 48-year-old male presented with 10 years of gradually enlarging yellow eyelid lesions. Past medical history was notable for adult-onset asthma diagnosed 5 years ago. He denied pain, diplopia, bone/joint pain, or systemic findings such as weight loss or fatigue. His father had similar eyelid lesions. Preoperative photograph demonstrated bilateral upper eyelid yellowish lesions with prominent edema and tissue expansion inducing bilateral ptosis (Fig. 1A). MRI demonstrated eyelid inflammation, enlargement of the extraocular muscles, especially the right lateral rectus (Fig. 1B, white arrow), and enlargement and enhancement of lacrimal gland (Fig. 1C, black arrow). He desired debulking excisional biopsies with bilateral blepharoplasty. Intraoperative photos show significant soft tissue inflammatory infiltration, particularly the lacrimal gland (Fig. 1D, red arrows).FIG. 1.Histopathologically, xanthogranulomatous inflammation is characterized by diffuse inflammatory infiltrate composed of histiocytes and lymphocytes (Fig. 2A, H&E, 100×). Specifically, the presence of foamy macrophages (Fig. 2B, H&E, 400×, red arrows) and Touton Giant cells (Fig. 2C, H&E, 400×, black arrow) are the histological hallmarks of the disease. The differential diagnosis of xanthogranulomatous inflammation includes adult-onset xanthogranuloma, adult-onset asthma with periocular xanthogranuloma (AAPOX), Erdheim-Chester disease (ECD), necrobiotic xanthogranuloma (NBX), and juvenile xanthogranuloma.FIG. 2.The patient was diagnosed with AAPOX given the association with adult-onset asthma. While the vast majority of yellow eyelid lesions are clinically benign, ECD and NBX are must-not-miss diagnoses, given their potential life-threatening systemic manifestations. These include vital organ (heart/kidney/lung) involvement in ECD, and association with serum protein abnormalities and hematological malignancies in NBX.

Wegener’s Granulomatosis Revealed by Bilateral Orbital Inflammatory Pseudotumor: a Case Report and Literature Review

Purpose: To describe the chronology and the extent of orbital involvement in a case of granulomatosis with polyangiitis (GPA). Methods: Descriptive case report and literature review. Results: A thirty-two years old male consulted with the following complaints: A retro-orbital discomfort in both eyes, a bilateral fast progressive proptosis and a decrease in visual acuity in the left eye. Eye examination revealed a proptosis, ptosis, epiphora and a motility restriction and peripheral corneal ulcer infiltrates with nodular scleritis in the left eye. A palpable orbital mass was located in the sub temporal orbit in both eyes. Orbit magnetic resonance imaging (MRI) unveiled a diffuse and elongated enlargement of both lacrimal glands with enhancing mass in the superior lateral aspect of both eyes globe. The diagnosis of an orbital pseudotumor was suspected. The biological work-up revealed a high blood levels of inflammation markers and antineutrophil cytoplasmic antibodies (c-ANCA). The diagnostic of active systemic granulomatosis with polyangiitis was then made. Conclusion: As seen in this case, clinicians should consider a differential diagnosis of granulomatosis with polyangiitis in patients with an orbital pseudotumor mimic aspect.

MEDICAL MANAGEMENT OF OCULAR SARCOIDOSIS

Sarcoidosis is one of the leading causes of inflammatory eye disease. Ocular sarcoidosis can involve any part of the eye and its adnexal tissues, and may cause uveitis, episcleritis/scleritis, eyelid abnormalities, conjunctival granuloma, optic neuropathy, lacrimal gland enlargement and orbital inflammation. Glaucoma and cataract can be complications from inflammation itself or adverse effects from therapy. Ophthalmic manifestations can be isolated, or associated with other organ involvement. Patients with ocular sarcoidosis can present with a wide range of clinical presentations and severity. Multi-disciplinary approaches are required to achieve the best treatment outcomes for both ocular and systemic manifestations.

Change in lacrimal gland volume and aqueous tear production following treatment with teprotumumab.

Dry eye syndrome occurs in up to 85% of patients with thyroid eye disease (TED). Lacrimal gland enlargement correlates with subjective tearing and a reduction in quality of life in patients with TED. In this prospective longitudinal study, patients presenting for the treatment of TED were considered for eligible. Primary outcomes included a change in the volume of the lacrimal gland and the production of tears following treatment with teprotumumab. The volume of lacrimal glands and proptosis was calculated using 3D volumetric analysis. Tear production was measured by Schirmer's test and associated symptoms were assessed using the VLSQ-8. The orbit with the most proptosis was designated the study orbit and the contralateral orbit was designated the fellow orbit. Twenty patients were included. Mean (SD) age was 61 (18) and mean duration of TED prior to therapy was 48 months (47). Lacrimal gland volume in the study orbit decreased from 768 mm3 (288) to 486 mm3 (173) (p < 0.01) following therapy. For the fellow orbit, volume reduced from 637 mm3 (261) to 379 mm3 (147) (p < 0.01). Schirmer's test reading (STR) in the study orbit increased from 14.5 mm (8.2) to 23 mm (10) (p < 0.01) (59%) following treatment. In the fellow orbit, STR increased from 12.7 mm (7) to 21 mm (9) post therapy (69%) (p < 0.01). There was a significant improvement on all parts of the VLSQ-8. Teprotumumab significantly reduces TED related expansion of the lacrimal gland, increases tear production, and improves dry eye symptoms.

Characteristics of Ocular Inflammatory Side Effects Associated with Immune Checkpoint Inhibitors in a Northern California Population

ABSTRACT Purpose To characterize the ocular inflammatory side effects associated with immune checkpoint inhibitor (CPI) treatment in a Northern California population. Design Retrospective case series. Participants Patients receiving CPI within an integrated healthcare delivery system. Methods All patients within Kaiser Permanente Northern California receiving CPI between January 1, 2012 and November 1, 2018 were identified. Medical records of those seen in the ophthalmology clinic at least once were retrospectively reviewed. Main Outcome Measures Type and duration of ocular inflammation, indication for and exposure to CPI, time from exposure to diagnosis of ocular inflammation. Results 31 cases of ocular inflammation were identified in 5061 patients (0.61%) receiving CPI. Mean ± SD age was 67 ± 11.9 (range 38–89). Mean time from exposure to diagnosis was 6.8 ± 5.5 months (range 0.5–17). 87% of cases were bilateral, and 43% of cases were chronic. Average ophthalmology follow-up was 16 ± 18 months (range 0–71). 16/31 (52%) had anterior uveitis, 7/31 (23%) had serous retinal detachment or panuveitis resembling Vogt-Koyanagi-Harada syndrome, 4/31 (13%) had papillitis, and 6/31 (19%) had diplopia or ocular motility defect. There was one case each (3.2%) of melanoma associated retinopathy, corneal edema, granulomatous lacrimal gland enlargement, and choroidal neovascularization. Conclusions Ocular inflammation is a rare immune associated side effect of CPI treatment, the most common manifestation of which is anterior uveitis.

The role of a conjunctival biopsy in the diagnosis of eosinophilic granulomatosis with polyangiitis with ocular involvement

A 33-year-old Asian man presented with redness, swelling, and blurring of vision in both eyes for 1 month associated with headache and pain. The patient had a history of allergic rhinitis with a progressive hearing loss for 3 months, followed by bell's palsy. Given his elevated serum cytoplasmic anti-neutrophil cytoplasmic antibody (C-ANCA) and erythrocyte sedimentation rate (ESR) levels as well as computed tomography head, orbit, and peripheral nervous system that showed marked bilateral mastoiditis with opacification of the right middle ear canal and enlargement of the bilateral lacrimal gland, the suspicion of small vessel vasculitis with ocular and ear involvement was high. Because there was no significant lung or kidney involvement, a conjunctival biopsy was attempted, which revealed small capillaries surrounded by eosinophils and plasma cells. Because there are no validated diagnostic tests for eosinophilic granulomatosis with polyangiitis (EGPA), a conjunctival biopsy can be valuable and minimally invasive in the early diagnosis and treatment of small vessel vasculitis.