Lacrimal gland measurements in patients with Graves’ ophthalmopathy

Assessment of morphometric and volumetric changes in lacrimal glands in thyroid eye disease, its clinical manifestations in relation of disease progression. Retrospective volumetric analysis included both genders and was performed on total of 183 patients - 91 patients with diagnosed Grave’s disease and thyroid eye disease and 92 patients without Grave’s disease and thyroid eye disease who underwent multidetector computed tomography (MDCT) examination in routine daily work according to other medical indications. In the group of females, there was statistical significance between patients with thyroid eye disease and controls who were smoking and had body weight gain. We found statistical significance in volumetric enlargements for both orbits in both genders for the patients group when compared to controls. There was also statistical significance in morphometric characteristics for the lacrimal gland diameters measured. Determination planimetric morphometric parameters of importance were coronary height of lacrimal gland of the right eye, coronary height of lacrimal gland of the left eye and coronary width of lacrimal gland of the left eye for the group of males. In a group of females the established determination parameters of importance were the coronary height of lacrimal gland of the left eye, the axial width of lacrimal gland of the left eye, volume of lacrimal gland of the right eye and the volume of lacrimal gland of the left eye. When we compared the displaced lacrimal gland coming forward (proptosis) in time progressing disease between group of patients and controls, we also found statistical significant connection. Evaluation of lacrimal gland volumetric and morphometric data may increase validity of defining this anatomical substrate and its morphology disruption as liable tool for thyroid eye disease progression follow up and treatment planning and outcome.

To determine if lacrimal dimensions are enlarged in Graves orbitopathy on CT and to correlate size with clinical data. One hundred and twenty-eight adult Caucasian patients with Graves orbitopathy who had CT at initial presentation to the authors' clinic were identified. The lacrimal gland width and length were measured on axial and coronal scans using the OsiriX software according to an established protocol. Comparison of dimensions with a published normal population was made. Clinical data near the time of CT were collected, including gender, age, smoking, subjective diplopia, exophthalmometry, intraocular pressure, corneal staining, and the VISA activity score for correlation with gland size. The lacrimal glands in Graves orbitopathy were significantly larger in all measured dimensions (p = 0.0001 for each dimension). There were no differences between the genders (p values ranged between 0.3855 and 0.8699). Exophthalmometry showed weak correlation with gland size in all dimensions (p value range, 0.0058 to <0.0001; r value range, -0.2616 to 0.4181). Smoking correlated significantly with gland enlargement in right coronal and axial width dimensions (p = 0.0150 and p = 0.0232, respectively). VISA inflammatory score was borderline correlated with right axial width. Lacrimal gland size did not correlate with diplopia, intraocular pressure, or corneal staining. The lacrimal gland is statistically significantly enlarged in Graves orbitopathy. Only weak correlation was found between gland enlargement and smoking, proptosis, and inflammatory activity. Future research will address the causal changes of enlargement and their effect on lacrimal function.

Harder's and lachrymal glands from 2000 rabbits and 200 hares have been studied to determine their histology and the relationship of the weight of the glands to the age, sex, and social status of the animals. The Harder's and lachrymal glands of hares were larger than those of rabbits. Sexual dimorphism was apparent in both species in the case of Harder's gland, the glands of males being larger than those of females. The lachrymal glands were the same size in male and female hares but slightly larger in male rabbits. The weight of both glands fluctuated seasonally in rabbits and hares, being largest during breeding. Harder's glands in dominant (sexually highly active) female and male rabbits on histological examination showed a higher degree of secretory activity. The Harder's glands of wild rabbits were larger in relation to body weight than those of domestic rabbits. The lachrymal glands were only slightly heavier in dominant male rabbits but the height of the secretory epithelium did not differ from that in the subordinate individuals. The size of the Harder's gland decreased in castrated male rabbits but increased in castrated females. The same effect was recorded for the lachrymal glands. Seasonal fluctuations in the weights of the central and lateral lobes of the submandibular glands in rabbits are reported.

A 57-year-old gentleman presented with a bilateral (OU) upper eyelid swelling since a month along with gritty sensation in the eyes. There was no history of systemic manifestations or similar family history. On examination, best corrected visual acuity (BCVA) in OU was 20/20 and N6 with Schirmer’s of 5 mm in the right eye (OD) and 3 mm in the left eye (OS), and ocular surface staining OU indicating aqueous deficiency dry eyes. Bilaterally, upper eyelid fullness was seen temporally along with S-shaped drooping of the eyelids [Fig. 1]. The superior orbital margin was palpable in OU along with mild tenderness. The palpebral lobe of the lacrimal gland was prolapsed and congested with surrounding chemosis. There was mild restriction of ocular motility on abduction. There was no evidence of proptosis. Intraocular pressure was 16 mmHg in OU. Posterior segment examination was within normal limits.Figure 1: (a) Shows bilateral upper eyelid fullness laterally and S-shaped lateral droop; (b) shows bilaterally prolapsed and congested palpebral lobes of the lacrimal gland, Figure 1c shows axial cut of the CT orbit showing a diffusely enlarged isodense lacrimal gland bilaterally, with no additional bony changesWhat is the next step? Radiological investigations Multilevel incisional biopsy with histopathologic confirmation Collagen vascular profile All of the above Correct Answer D. All of the above Diagnosis and Management Table 1 shows the clinical characteristics of common lacrimal gland disorders. Considering the possibility of subacute dacryoadenitis involving the orbital and palpebral lobes of the lacrimal gland, radiological investigation was done in the form of computed tomography (CT), which showed bilaterally bulky lacrimal glands abutting the lateral rectus on both the sides along with slightly bulky appearance of the lateral recti. A multilevel incisional biopsy was performed for the patient, and histopathology and immunohistochemistry confirmed the diagnosis of IgG4-related dacryoadenitis. A detailed collagen vascular profile was done to evaluate all underlying collagen vascular diseases. Out of the panel, serum IgG4 was found to be raised, therefore correlating with the histopathology. The patient was treated with intravenous methyl prednisolone 500 mg pulse therapy for six pulses along with topical lubricants. He started responding by the fourth cycle and at the latest follow-up of 2 years and 8 months, he is doing extremely well with normalized serum IgG4 levels and resolution of ocular symptoms with Schirmer’s improved to 10 mm in OU.Table 1: Clinical characteristics of lacrimal gland disordersDiagnosis OU IgG4-related dacryoadenitis with severe dry eyes. Discussion Over the last two decades, the unidentified zone of IgG4-related disease has been duly explored. The disease mimics a broad spectrum of clinical entities, ranging from neoplastic to inflammatory and even infectious conditions, which makes it mandatory for the clinicians to understand the clinical presentation, possible differentials, management, and prognosis of IgG4-related disease. Ophthalmologically, the patients present with diplopia, ptosis, visual acuity, disturbance, ocular motility restriction, dry eyes, corneal ulcer, or epiphora.[1] Baseline radiological imaging followed by surgical biopsy would be appropriate.[2] Systemic correlation rules out its presentation as sialadenitis, pancreatitis, and lymphadenopathy as well.[1] Serum IgG4 levels are confirmatory as well as prognostic. The disease responds well to treatment with steroids, but has follows a chronic course with systemic morbidity if left undiagnosed and untreated as it causes end-stage organ failure.[3] Therefore, this possible differential diagnoses and the low remission rate of 23.8% must be kept in mind in a patient with dacryoadenitis presenting with dry eyes.[4] Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his names and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

The Harderian gland is an orbital gland thought to be a source of corneal lubricant, supplementary to the other orbital glands. This study investigated the possible role of skink Harderian glands in corneal lubrication. It was hypothesized that if these glands play a role in corneal lubrication, then the structure of these glands would be affected by structural orbital modifications. We examined the Harderian and lacrimal glands of five species of Australian skinks (Lygosominae), two of which possessed orbital modifications in the form of a transparent immoveable eyelid (spectacle) and skull reduction. All species possessed well-developed posterior lacrimal glands, but no anterior lacrimal glands. Anatomically, the Harderian glands were smaller in the burrowing species relative to the nonburrowing species. No other obvious species-specific differences were observed. The absence of any differentiation at the microscopic level suggests that although there is some change in the relative amount of secretant produced, the nature of the secretion studied by classical histochemistry remains essentially unchanged. However, at higher taxonomic levels, the size and structure of the Harderian gland may be taxon-specific and unrelated to the orbital environment. Thus, orbital lubrication may not necessarily be the sole function of the Harderian gland.

Orbital cholesterol granuloma: A report and discussion of orbital findings

Purpose: We report two cases of crocodile tear syndrome following facial nerve palsy, in which both symptoms and objective findings improved after lacrimal gland injection of botulinum toxin A.Case summary: Case 1: A 36-year-old man with a history of left facial palsy reported excessive tearing in the left eye during meals. External ocular examination and lacrimal drainage tests were unremarkable. The baseline Schirmer test measured 9 mm, which increased to 23 mm during mastication, confirming the diagnosis of crocodile tear syndrome. Four weeks after botulinum toxin A injection into the lacrimal gland, the Schirmer test value during chewing decreased to 13 mm, and the Munk score improved from 3 to 1. Case 2: A 40-year-old man with a history of right facial nerve palsy presented with excessive tearing in the right eye during meals. External ocular examination and lacrimal drainage tests were normal. The baseline Schirmer test measured 13 mm, which increased to 29 mm during mastication, consistent with crocodile tear syndrome. Four weeks after botulinum toxin A injection into the lacrimal gland, the Schirmer value during chewing decreased to 14 mm, and the Munk score improved from 4 to 1.Conclusions: Lacrimal gland injection of botulinum toxin A effectively reduces symptoms and improves subjective and objective outcomes in crocodile tear syndrome.

Gross Characteristics of Normal Human Lacrimal Glands

Radioiodine (RAI) is used in the treatment of hyperthyroidism and differentiated thyroid cancer. Radioiodine therapy is associated with dry eyes and some side effects are seen especially due to beta rays. In this study, the functional and cytological status of lacrimal glands after RAI therapy was evaluated. Twenty-five patients with a mean age of 55.16 years with planned low-dose RAI therapy were evaluated. Just before and 6 months after the treatment, the lacrimal glands were evaluated with tear break-up time (BUT), Schirmer's test, impression cytology and "Ocular Surface Disease Index (OSDI)" questionnaire. The mean value of Schirmer's test was 16.20 ± 3.61 pre-treatment and 11.28 ± 4.39 post-treatment for the right eye, and 15.76 ± 3.27 and 10.60 ± 4.42 for the left eye, respectively. The mean value of Schirmer's test decreased significantly post-treatment in both eyes (p = 0.0001). The BUT score also decreased significantly post-treatment (p = 0.001). The mean value of OSDI score was 27.5 ± 8.02 pre-treatment and 46.36 ± 10.27 post-treatment. The mean value of OSDI score increased post-treatment (p = 0.0001). The impression scores also increased post-treatment in both eyes (p = 0.0001). Even low-dose (≤30 mci) RAI treatment affects lacrimal gland functions. Low-dose RAI causes a decrease in the value of Schirmer's test and the BUT test, and an increase in the value of OSDI score and impression scores.

PurposeTo evaluate the physiological distribution and tumour detection ability of [18F]AlF-PSMA-11 positron emission tomography (PET) dual-phase scans in patients with prostate cancer (PCa).MethodsAs a retrospective study, clinical and PET data of PCa patients who underwent dual-phase [18F]AlF-PSMA-11 PET of routine scan (45–50 min) and delayed scan (120 min) from November 2020 to June 2021 were collected, and physiological and pathological regions of interest were quantified to determine the time-dependent maximum standardized uptake value (SUVmax) of [18F]AlF-PSMA-11. Part of the above subjects who underwent [68Ga]Ga-PSMA-11 PET in the following 6 months were included in a head-to-head comparison. The difference with a p-value < 0.05 was defined as statistical significance. Diagnosis accuracy of primary and metastatic lesions was measured referring to the surgical findings, pathology, and follow-up imaging.Results[68Ga]Ga-PSMA-11 and [18F]AlF-PSMA-11 were of the comparable uptake in glands in head, but the latter was of a significant lower distribution in liver and spleen. For the 25 patients initially diagnosed with prostate cancer and 3 patients with biochemical recurrence after radical surgery, the SUVmax of the primary lesions, lacrimal glands, parotid glands and submandibular glands was higher at 120 min compared to that at 45–50 min, but not a significant difference. SUVmax of the liver, spleen and bladder decreased significantly at 120 min, but the bladder SUVmax remained higher than that of primary lesions. SUVmax of the kidneys and centrum was the same in dual-phase scans. For the 31 primary lesions detected in [18F]AlF-PSMA-11 PET, both the SUVmax of the two phases kept the positive correlation with PSA, Gleason score and initial risk stratification. For the 39 distant metastatic lesions, 94.87% accuracy of routine scan and 100% accuracy of delayed scan were acquired, and 7.14% patients (2/28) benefited from the dual-phase [18F]AlF-PSMA-11 scans that revealed novel information on metastatic lesions compared to the routine scan.Conclusion[18F]AlF-PSMA-11 PET expanded the time window and further decreased metabolic background of [68Ga]Ga-PSMA-11 PET. The dual-phase scan of [18F]AlF-PSMA-11 PET can benefit prostate cancer diagnosis via providing more PSMA-specific information.

Case presentation: A 32-year-old female patient was referred to the emergency department by the ophthalmologist due to the complaint of low visual acuity in the left eye. The patient reported progressive blurred vision in the left eye which had begun one year ago. Two months ago she noticed significant worsening of the symptoms leading to unilateral amaurosis. She was then hospitalized in another institution, where it was performed a skull computed tomography, which showed infiltration of the optic nerve. She then received a presumed diagnosis of neuromyelitis optica (NMO). It was prescribed pulse therapy and the patient was discharged with prednisone 80 mg/day. One month later, she was evaluated in our hospital presenting a persistent headache, pain when moving the left eye and blurred vision in the right eye. An investigation was carried out, and evidenced pachymeningitis on skull MRI and normal rheumatological tests, except for ANA, which was 1:640. Lumbar puncture had no abnormalities. Because of these findings, it was suspected of a granulomatosis disease and it was necessary to perform a meningeal biopsy. The immunohistochemical analysis confirmed pachymeningitis for IgG4-related disease (IgG4-RD). Discussion: IgG4-RD is an inflammatory disorder, immune mediated and it can affect multiple organs and systems, which can lead to fibrosis and tissue destruction. Any organ might be involved, but pancreas, biliary tract and lacrimal glands are most often affected. Neurologically, the disease is relevant due to the possibility of affecting the orbits, pituitary gland, meninges, peripheral nerves and even the brain. It usually affects individuals between 50-80 years old. Autoimmune pancreatitis affects both man and women in a proportion of 4:1. IgG4-RD is usually indolent, although acute and subacute manifestations are common when there is vascular involvement. In this case, significant involvement of the pachymeninges was observed with infiltration at the level of the optic foramen bilaterally, more evidently on the left, in addition to the orbital apex on the left and the retropharyngeal space. Infectious hypotheses were ruled out, serum IgG4 level was normal. CSF IgG4 level was not available. In the biopsy, lymphoplasmacytic predominance was noted with an IgG4:IgG ratio &gt; 60%. Treatment with corticosteroids was started and continued with a biannual infusion of Rituximab. Final comments: Early consideration of IgG4-RD in differential diagnosis is crucial, as prompt diagnosis improves response to corticosteroid treatment. Delayed diagnosis can lead to irreversible fibrotic changes and permanent disabilities. Our patient spent over a year from the onset of symptoms until diagnosis. Despite the use of anti-CD20 therapy, the patient continues to show disease progression, highlighting concerns regarding limited therapeutic options and evidence.

Proliferation of Lacrimal Gland Acinar Cells in Primary Culture. Stimulation by Extracellular Matrix, EGF, and DHT

Background/Aims: Establish a reliable rabbit dry eye (DE) model. Methods: An interventional cohort study surgically removing glands contributing to the tear film. Eight rabbits were studied after removal of left lacrimal, Harderian, or both glands. Additional rabbits had Meibomian glands in the left eye thermally obstructed. All were followed for 10 weeks with phenol red thread (PRT) and slit-lamp examination with 2% fluorescein. We assessed corneal sensitivity using a Cochet-Bonnet esthesiometer. Outcome measures were severity/duration of reduced PRT, punctate epithelial erosions (PEE), and histologic evidence of corneal pannus. Results: Fluorescein staining demonstrated signs of dryness including PEE in all of the interventional eyes. The subjective measurement of epithelial erosions correlated with decreased tear production. PRT measurements in the control eyes averaged 31.54 mm (±1.83) and 22.71 mm (±1.60) in the eight left eyes, without loss of corneal sensitivity. Conclusions: Surgical removal of either the Harderian or lacrimal gland results in statistically significant decreases in tear volume and the development of severe DE. Removal of both glands results in the occurrence of a DE of comparable severity/duration to removal of either the lacrimal or Harderian gland alone. Meibomian gland obstruction contributes less to the DE model.

The purpose of this report was to describe the ocular findings in Myelodysplasia, Infection, Restriction of growth, Adrenal hypoplasia, Genital problems, and Enteropathy (MIRAGE) syndrome, a multisystem congenital disorder. This was a case report and literature review. An infant with MIRAGE syndrome (combined immunodeficiency with recurrent infections, growth restriction, adrenal insufficiency, 46,XY karyotype with hypovirilization, dysphagia, gastroesophageal reflux disease, and dysautonomia) underwent ophthalmological evaluation because of persistent conjunctivitis during his 8-month admission in the neonatal intensive care unit. His parents noted absence of tears when crying since birth. Bilateral broad corneal epithelial defects were noted, and treatment was initiated with frequent lubricating ointment. At 9 months, his vision was estimated at 20/380 in both eyes using Teller Acuity Cards. There were persistent bilateral epithelial defects, confluent punctate epithelial erosions, low Schirmer strip wetting (right eye 3 mm and left eye 2 mm), and decreased corneal sensation. Brain magnetic resonance imaging images demonstrated hypoplastic lacrimal glands bilaterally. More aggressive lubrication and installation of punctal plugs in all 4 lids were successful at preventing further epithelial defects. This case presents deficient lacrimation as a manifestation of MIRAGE syndrome and is the first to identify lacrimal gland hypoplasia and corneal anesthesia. Autonomic and neurologic dysfunction have been proposed to play a role in the pathophysiology of hypolacrimation in similar syndromes and likely contributed to the poor ocular surface in this case. Patients with MIRAGE should undergo ophthalmic assessment as soon as possible after birth because early intervention is essential to preventing irreversible corneal damage.

Case summaryA 14-year-old female spayed Abyssinian cat, which about 1 year previously underwent thoracic limb amputation, radiotherapy and chemotherapy for an incompletely excised vaccine-related fibrosarcoma, was presented for evaluation of corneal opacity in the left eye (OS). The ocular surface of both eyes (OU) had a lackluster appearance and there was a stromal corneal ulcer OS. Results of corneal aesthesiometry, Schirmer tear test-1 (STT-1) and tear film breakup time revealed corneal hypoesthesia, and quantitative and qualitative tear film deficiency OU. Noxious olfactory stimulation caused increased lacrimation relative to standard STT-1 values suggesting an intact nasolacrimal reflex. Various lacrimostimulants were administered in succession; namely, 1% pilocarpine administered topically (15 days) or orally (19 days), and topically applied 0.03% tacrolimus (47 days). Pilocarpine, especially when given orally, was associated with notable increases in STT-1 values, but corneal ulceration remained/recurred regardless of administration route, and oral pilocarpine resulted in gastrointestinal upset. Tacrolimus was not effective. After 93 days, the cat became weak and lame and a low thyroxine concentration was detected in serum. The cat was euthanized and a necropsy performed. Both lacrimal glands were histologically normal, but chronic neutrophilic keratitis and reduced conjunctival goblet cell density were noted OU.Relevance and novel informationThe final diagnosis was dry eye syndrome (DES) of presumed neurogenic origin, associated with corneal hypoesthesia. This report reinforces the importance of conducting tearfilm testing in cats with ocular surface disease, as clinical signs of DES were different from those described in dogs.