Kinematics of the Upper Eyelid and the Globe During Downward Excursion With Comparative Analysis in Patients With Thyroid Eye Disease.

PURPOSE: To analyze the kinematics of the upper eyelid and the globe on downward excursion for potential use in monitoring thyroid eye disease (TED) progression in an objective manner. METHODS: Ten normal volunteers and 10 patients with TED were studied. A high-speed (240 fps) digital camera with a coaxial light source set at a constant distance from the subjects' eyes was used to record the excursion of the upper eyelid and the globe from extreme upgaze to extreme downgaze. Clinical data, including age, gender, race, thyroid function tests, Vision, Inflammation/Congestion, Strabismus/motility restriction, Appearance/exposure score (primary surgeons' preference of TED grading system), exophthalmometry, and eyelid measurements were collected for all patients with TED. Frame-by-frame analyses of the videos were performed using Python software (version 3.6) and the Open Source Computer Vision Library. Temporal resolution was obtained by measuring the number of frames from initiation of eyelid and globe movement from extreme upgaze (t 0 ) to extreme downgaze (t f ). Spatial resolution was obtained by measuring the number of pixels the eyelid margin and the globe traversed from t 0 to t f . The data were then plotted on a graph to calculate the velocity of the upper eyelid and the globe during downward excursion. RESULTS: Velocimetric calculations using high-speed photography suggests that downward excursion of the upper eyelid, and the globe occurs in 2 phases: the acceleration phase and the deceleration phase. Comparative analysis of slow-motion videography demonstrates that patients with TED were found to have attenuation in the early acceleration phase of upper eyelid excursion compared with normal subjects. In patients with TED, the difference in velocity between the eyelid and the globe occurs in the early deceleration phase. CONCLUSIONS: The upper eyelid normally synchronizes intimately with the globe during downward eye movement. Data from this study reveal that attenuation mostly in the early deceleration phase of eyelid movement relative to the globe accounts for the dynamic eyelid lag seen on clinical examination. Further analysis is needed to show if a quantified von Graefe sign can be used as an objective means of monitoring progression in TED.

Gene Expression Profiling and Heterogeneity of Nonspecific Orbital Inflammation Affecting the Lacrimal Gland.

Importance: Although a variety of well-characterized diseases, such as sarcoidosis and granulomatosis with polyangiitis, affect the lacrimal gland, many patients with dacryoadenitis are diagnosed as having nonspecific orbital inflammation (NSOI) on the basis of histology and systemic disease evaluation. The ability to further classify the disease in these patients should facilitate selection of effective therapies. Objective: To test the a priori hypothesis that gene expression profiles would complement clinical and histopathologic evaluations in identifying well-characterized diseases and in subdividing NSOI into clinically relevant groups. Design, Setting, and Participants: In this cohort study, gene expression levels in biopsy specimens of inflamed and control lacrimal glands were measured with microarrays. Stained sections of the same biopsy specimens were used for evaluation of histopathology. Tissue samples of patients were obtained from oculoplastic surgeons at 7 international centers representing 4 countries (United States, Saudi Arabia, Canada, and Taiwan). Gene expression analysis was done at Oregon Health & Science University. Participants were 48 patients, including 3 with granulomatosis with polyangiitis, 28 with NSOI, 7 with sarcoidosis, 4 with thyroid eye disease, and 6 healthy controls. The study dates were March 2012 to April 2017. Main Outcomes and Measures: The primary outcome was subdivision of biopsy specimens based on gene expression of a published list of approximately 40 differentially expressed transcripts in blood, lacrimal gland, and orbital adipose tissue from patients with sarcoidosis. Stained sections were evaluated for inflammation (none, mild, moderate, or marked), granulomas, nodules, or fibrosis by 2 independent ocular pathologists masked to the clinical diagnosis. Results: Among 48 patients (mean [SD] age, 41.6 [19.0] years; 32 [67%] female), the mclust algorithm segregated the biopsy specimens into 4 subsets, with the differences illustrated by a heat map and multidimensional scaling plots. Most of the sarcoidosis biopsy specimens were in subset 1, which had the highest granuloma score. Three NSOI biopsy specimens in subset 1 had no apparent granulomas. Thirty-two percent (9 of 28) of the NSOI biopsy specimens could not be distinguished from biopsy specimens of healthy controls in subset 4, while other examples of NSOI tended to group with gene expression resembling granulomatosis with polyangiitis or thyroid eye disease. The 4 subsets could also be partially differentiated by their fibrosis, granulomas, and inflammation pathology scores but not their lymphoid nodule scores. Conclusions and Relevance: Gene expression profiling discloses clear heterogeneity among patients with lacrimal inflammatory disease. Comparison of the expression profiles suggests that a subset of patients with nonspecific dacryoadenitis might have a limited form of sarcoidosis, while other patients with NSOI cannot be distinguished from healthy controls.

Axial Globe Position Measurement: A Prospective Multicenter Study by the International Thyroid Eye Disease Society.

PURPOSE: Identify a reproducible measure of axial globe position (AGP) for multicenter studies on patients with thyroid eye disease (TED). METHODS: This is a prospective, international, multicenter, observational study in which 3 types of AGP evaluation were examined: radiologic, clinical, and photographic. In this study, CT was the modality to which all other methods were compared. CT AGP was measured from an orthogonal line between the anterior lateral orbital rims to the cornea. All CT measurements were made at a single institution by 3 individual clinicians. Clinical evaluation was performed with exophthalmometry. Three clinicians from each clinical site assessed AGP with 3 different exophthalmometers and horizontal palpebral width using a ruler. Each physician made 3 separate measurements with each type of exophthalmometer not in succession. All photographic measurements were made at a single institution. AGP was measured from lateral photographs in which a standard marker was placed at the anterior lateral orbital rim. Horizontal and vertical palpebral fissure were measured from frontal photographs. Three trained readers measured 3 separate times not in succession. Exophthalmometry and photography method validity was assessed by agreement with CT (mean differences calculation, intraclass correlation coefficients [ICCs], Bland-Altman figures). Correlation between palpebral fissure and CT AGP was assessed with Pearson correlation. Intraclinician and interclinician reliability was evaluated using ICCs. RESULTS: Sixty-eight patients from 7 centers participated. CT mean AGP was 21.37 mm (15.96-28.90 mm) right and 21.22 mm (15.87-28.70 mm) left (ICC 0.996 and 0.995). Exophthalmometry AGP fell between 18 mm and 25 mm. Intraclinician agreement across exophthalmometers was ideal (ICC 0.948-0.983). Agreement between clinicians was greater than 0.85 for all upright exophthalmometry measurements. Photographic mean AGP was 20.47 mm (10.92-30.88 mm) right and 20.30 mm (8.61-28.72 mm) left. Intrareader and interreader agreement was ideal (ICC 0.991-0.989). All exophthalmometers' mean differences from CT ranged between -0.06 mm (±1.36 mm) and 0.54 mm (±1.61 mm); 95% confidence interval fell within 1 mm. Magnitude of AGP did not affect exophthalmometry validity. Oculus best estimated CT AGP but differences from other exophthalmometers were not clinically meaningful in upright measurements. Photographic AGP (right ICC = 0.575, left ICC = 0.355) and palpebral fissure do not agree with CT. CONCLUSIONS: Upright clinical exophthalmometry accurately estimates CT AGP in TED. AGP measurement was reliably reproduced by the same clinician and between clinicians at multiple institutions using the protocol in this study. These findings allow reliable measurement of AGP that will be of considerable value in future outcome studies.

Cervical occupational hazards in ophthalmic plastic surgery.

PURPOSE OF REVIEW: To increase awareness of cervical musculoskeletal disorders (cMSD) in ophthalmic plastic surgeons (OPS) and review strategies for management and prevention. RECENT FINDINGS: There are objective data that show OPS spend the majority of their time operating in awkward, prolonged, static, asymmetric postures. These postures increase cervical load and cMSD. Loupes and headlamps further increase this cervical loading by 40%. Risk for cMSD is not limited to the operating room. Muscular demands in the anterior deltoid and cervical trapezius are increased in slit lamp biomicroscopy and indirect ophthalmoscopy. Furthermore, the majority of the office visit is spent keyboarding into the electronic medical record which is associated with cMSD. Habitual postural faults result from these cumulative exposures. These must be addressed to prevent further insult and debilitating injury. Successful management requires education in neutral posture, therapeutic exercise, environmental adjustments in the workplace and home, and supported neutral sleep posture. SUMMARY: The risks of cMSD in OPS are well established, and nearly 10% of cervical injury will end a career. Neck pain must not be ignored, and experienced professional help is critical. A long-term approach that incorporates exercise, manual therapy, and education is essential for management and prevention.

Transcranial orbital decompression for progressive compressive optic neuropathy after 3-wall decompression in severe graves' orbitopathy.

PURPOSE: To determine surgical outcomes after transcranial decompression of the superior orbit in patients with progressive compressive optic neuropathy (CON) secondary to Graves' orbitopathy (GO) who had previously been treated with 3-wall decompression. METHODS: Approval from the West Virginia University Institution Review Board was obtained. A retrospective review of 4 patients with GO who received bilateral transcranial decompression of the orbits for progressive compressive optic neuropathy after bilateral maximal extracranial 3-wall decompression was performed. The patients were treated by the Multidisciplinary Orbit and Skull Base Services at West Virginia University and the University of Michigan. RESULTS: Bilateral transcranial decompression of the orbit for GO was performed on 8 orbits in 4 patients. All 8 orbits had radiographic evidence of compression of the orbital apex, and all patients had been treated with steroids, orbital radiation, and bilateral 3-wall decompression. Preoperative vision ranged from 20/25 to 20/100, which improved to 20/25 or better in all eyes. The visual field mean deviation improved from a mean of -13.05 to -1.67 dB. Hertel measurements improved from a mean of 19.25 to 15.25 mm. Extraocular motility was essentially unchanged. Two patients were noted to have asymptomatic ocular pulsations. There were no other complications, and all patients remained stable during a follow-up period of 5 years (range 2-8 years). CONCLUSIONS: Transcranial decompression is an effective and safe method of salvaging vision when standard treatments fail. This is only the second report of transcranial decompression for refractory compressive optic neuropathy after decompression from a standard approach.

Calculated computed tomography volumes of lacrimal glands and comparison to clinical findings in patients with thyroid eye disease.

PURPOSE: To describe the range of lacrimal gland volumes on CT in Caucasian patients with thyroid eye disease (TED) and to correlate with clinical findings. METHODS: With institutional review board approval, 125 orbital CT scans for TED were reviewed. OsiriX software was used to calculate the volume of the lacrimal gland. Comparison of the volumes was made with previously published results of the normal population. Patient race, gender, smoking status, diplopia, tearing, exophthalmometry, superficial punctate keratitis (SPK), lagophthalmos, restriction in motility, and VISA score were collected. RESULTS: The mean volume of the lacrimal gland in patients with TED was 0.890 cm in right orbits (standard deviation [SD] 0.348), 0.851 cm in left orbits (SD 0.350), with no significant difference between right and left (p = 0.311). The mean volume was 0.811 cm in right male orbits (SD 0.386) and 0.911 cm in right female orbits (SD 0.335), with no significant difference between men and women (p = 0.774). These findings were confirmed in an analysis of left orbits. The volume of right and left orbits correlated well (r = 0.777, p < 0.0001). The lacrimal gland volume in patients with TED was greater compared with the normal population using a 2-sample t test (p < 0.0001). Exophthalmometry (right: r = 0.225, p = 0.0115; left: r = 0.267, p = 0.0026) and subjective tearing (right: r = 0.226, p = 0.0138; left: r = 0.197, p = 0.0322) correlated with lacrimal gland volume. CONCLUSIONS: This study is the first to report the volume of the lacrimal gland calculated on CT scan for patients with TED. The lacrimal gland is larger in patients with TED and correlates with subjective tearing and exophthalmometry.

Calculated CT volumes of lacrimal glands in normal Caucasian orbits.

INTRODUCTION: The objective was to describe the range of normal volumes for the lacrimal gland calculated from CT. METHODS: A retrospective review with institutional review board approval of 293 CT scans of 586 orbits was performed. Patients were included if they were Caucasian and aged 18 years or older. Orbits were excluded if there was a disease or trauma. OsiriX software was used to outline the lacrimal gland in consecutive axial slices and to calculate the volume. Inter-rater agreement was assessed in a subset of 30 randomly selected orbits by observers of different levels of training using the intraclass correlation coefficient (ICC). RESULTS: Two hundred sixty orbits of 187 patients were included. The mean volume of the lacrimal gland was 0.696 cm2 in right orbits (SD = 0.261) and 0.649 cm2 in left orbits (SD = 0.231), with no significant difference between right and left (p= 0.125). The mean volume was 0.680 cm2 in men (SD = 0.241) and 0.662 cm2 in women (SD = 0.260), with no significant difference between men and women (p = 0.564). There was an inverse relationship between gland volume and age (Pearson r= -0.428 right orbits and -0.469 left orbits). Of the 73 bilateral patients, right and left orbits correlated well (Pearson r = 0.712). Agreement was good among the observers (ICC = 0.727). CONCLUSIONS: This is the first study to report the range of normal volume for Caucasian lacrimal glands measured on CT scans. The volume of the lacrimal gland decreases with age, and there is no gender or laterality difference.

Bilateral diffuse orbital myositis in a patient with relapsing ulcerative colitis.

Ophthalmic manifestations of inflammatory bowel disease are common, but orbital inflammatory disease is rare with most cases associated with Crohn disease. We describe the first case of bilateral, diffuse, orbital myositis associated with ulcerative colitis in a patient taking infliximab. Within 72 hours of intravenous methylprednisolone treatment, the orbital inflammation dramatically improved. After 8 weeks of prednisone, it completely resolved and has remained quiet for 13 months. This is only the third report of ulcerative colitis-associated orbital inflammatory disease.

CT dimensions of the lacrimal gland in Graves orbitopathy.

PURPOSE: To determine if lacrimal dimensions are enlarged in Graves orbitopathy on CT and to correlate size with clinical data. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Delayed Eikenella corrodens orbital infection after fracture repair.

Orbital cellulitis and abscess after fracture repair are rare. Ophthalmic infection with Eikenella species is even more unusual, but can be severe. We report a case of Eikenella corrodens infection in a 28-year-old man who underwent zygomaticomaxillary and orbital floor blowout fracture surgery 4 years before presentation. Eikenella species are often resistant to frequently used empiric antibiotics, and because of specific growth conditions, easily missed on standard cultures. Appropriate efforts should be made to identify and treat E. corrodens in atypical orbital and periocular infections.

Computed tomography dimensions of the lacrimal gland in normal Caucasian orbits.

INTRODUCTION: CT is frequently used to assess the lacrimal gland, yet no published reports exist of normal dimensions using this modality. We retrospectively evaluated CT data from normal orbits and measured the lacrimal gland dimensions. METHODS: Two-hundred ninety-three consecutive orbital CT scans (586 orbits) of 282 patients were identified. Caucasian patients aged 18 years and older without known orbital disease were included. Traumatized orbits were excluded. All repeated scans were excluded. Length and width of the lacrimal gland were measured in axial and coronal sections with GE Centricity Software. The primary outcome was a descriptive analysis of the distribution of dimensions in normal orbits. A random subset of patient scans was measured independently by observers at different levels of training, and intraclass correlation coefficients (ICCs) were established. RESULTS: Three hundred orbits (150 right orbits and 150 left orbits) of 282 patients were included. Normal distributions occurred with axial and coronal length measurements. Mean (10th and 90th percentiles) lacrimal gland axial length in right orbits was 14.7 mm (10.9 mm and 18.3 mm) and 14.5 mm in left orbits (10.3 mm and 18.3 mm). Coronal length averaged 17.7 mm in right eyes (13.9 mm and 21.8 mm) and 16.9 mm in left eyes (12.8 mm and 20.8 mm). Axial and coronal width showed non-normal distributions. No statistically significant difference in dimensions was found between genders, and a significant inverse linear relation occurred between gland size and age. Agreement was significant among the observers (ICC >0.7). CONCLUSION: This study presents a normal range of Caucasian lacrimal gland dimensions seen on CT. Lacrimal gland size decreases with age, and no gender difference exists. This range can aid in differentiating diseased and nondiseased lacrimal glands, especially when correlated with physical examination. This may be useful in clinical trials that involve lacrimal gland size.

A survey study of occupational pain and injury in ophthalmic plastic surgeons.

PURPOSE: To determine factors associated with pain/injury related to practicing ophthalmic plastic and reconstructive surgery. METHODS: A 29-question electronic survey was sent to the American Society of Ophthalmic Plastic and Reconstructive Surgery's listserv. The Chi-Squared Automatic Interaction Detector technique was used to generate a decision tree using SPSS software. The levels of dendograms were limited to 8. Significance was pre-established at α = 0.05. RESULTS: One hundred thirty surveys were completed, and 72.5% reported pain associated with operating, 80.9% reported use of loupe magnification, 68.7% reported use of a headlight, 42.5% reported modification of their operating room practice, and 9.2% reported stopping operating due to pain or spine injury. Most respondents regularly exercise, with 55.7% characterizing the amount of exercise as less than necessary; 60.8% and 57.3% agreed that loupe use and headlamp use, respectively, can lead to spine problems.Chi-Squared Automatic Interaction Detector analysis found that 62.7% (n = 47) with neck pain had modified their operating room practice, compared with 13.5% (n = 7) without pain (χ = 30.42; df = 1; p < 0.001); All surgeons that had to stop operating (n = 9) had tried modifying their operating room practice; over half (57.6%, n = 38) of practicing surgeons had changed their operating room practice (χ = 6.09; df = 1; p = 0.014). The majority who exercised 5 hours or less had modified their operating room practice (70.2%, n = 33), compared with 26.3% (n = 5) who exercised more. CONCLUSIONS: Many oculoplastic surgeons experience discomfort due to operating, and an alarming minority have stopped operating due to pain or neck injury. Participants identified loupe and headlamp use as a special concern.

North American blastomycosis of the eyelid.

A 26-year-old diabetic man presented with a papillomatous eyelid lesion. Histopathology was consistent with Blastomyces dermatitidis. A 1-year course of itraconazole led to resolution in this case. Although skin is the most common extrapulmonary site of blastomycosis, eyelid involvement is rare. Prompt diagnosis and treatment improve morbidity and mortality.

Chordoma of the anterior cranial fossa and ethmoids with orbital involvement.

PURPOSE: To report a case of orbital chordoma, emphasizing the clinical, operative, and histopathologic findings, and to review similar English-language reports. METHODS: This is a single case report with histopathologic correlation. Search of the English-language literature and review of referenced citations was performed. RESULTS: After treatment with resection and proton beam radiation, our patient is alive, without recurrence at 3-year follow-up. Biopsy of the recurrent tumor was consistent with chordoma. The original biopsy had S100 and pancytokeratin-positive tumor cells, with abundant clear to eosinophilic cytoplasm. Focal EMA positivity was present. Literature review identified 14 additional cases. CONCLUSION: Orbital chordoma is rare. Extraocular motility disturbances occur solely with intracranial lesions as well as those extending into the orbit, but globe displacement is the most common sign of orbital involvement. This tumor often recurs in the path of previous resection. Diagnosis is confirmed by distinctive histopathologic features and positive staining for S100, pancytokeratin, and EMA. Treatment and outcome analysis of orbital chordoma is difficult due to its rarity and lack of reported follow-up and may need to be extrapolated from reported skull base cases.

Modified tarsal resection operation for congenital ptosis with fair levator function.

PURPOSE: There are many options for surgical repair of congenital ptosis with fair levator function. The authors review their 10-year experience with an en bloc resection of tarsus, Müller muscle, and conjunctiva in conjunction with graded levator aponeurosis advancement (a variation of the tarsectomy operation). METHODS: This is a retrospective case series that reviews all cases of ptosis repair performed at West Virginia University from 1994 to 2004 using the "modified tarsal resection method." Thirty patients with congenital ptosis and fair levator function were identified. Follow-up ranged from 6 weeks to 8 years. Charts were reviewed for type of ptosis, pre- and postoperative upper eyelid margin to reflex distance, degree of levator function, amount of operative tarsus and Müller muscle resection, postoperative eyelid symmetry, and postoperative complications. RESULTS: In patients with congenital ptosis and fair levator function, the average preoperative upper eyelid margin to reflex distance was 0.0 mm and the average postoperative upper eyelid margin to reflex distance was 2.8 mm. Twenty-five of 30 (83%) patients were deemed to have a "good" surgical outcome. The amount of tarsus-Müller muscle resection reliably predicts the amount of eyelid elevation. The only complications to date have been transient lagophthalmos with exposure keratitis. CONCLUSIONS: In the authors' hands, an en bloc resection of tarsus, Müller muscle, and conjunctiva combined with levator aponeurosis advancement reliably produces excellent results in the treatment of fair levator function congenital ptosis, superior to their previous experience with isolated maximal levator aponeurosis advancement.

Mycobacterium fortuitum infection masquerading as an orbital mass.

Orbital infection with nontuberculous mycobacteria is rare and usually presents as an inflammatory process. We report a case of a 34-year-old male hospital worker with a positive purified protein derivative skin test who had Mycobacterium fortuitum infection that presented as an orbital mass causing diplopia. This presentation is unlike previously published reports and demonstrates the importance of orbital biopsy and tissue culture.

Infiltrating orbital astrocytic proliferation associated with congenitally malformed eyes.

This report describes the clinical and pathologic findings in two adults with orbital infiltration by astrocytic cells associated with congenitally malformed eyes. Both cases had enlarging orbital masses and underwent complete resection. Histopathology revealed proliferation of astrocytes (fibrillary acidic protein-positive) that invaded the orbital tissues. To the best of our knowledge, there are no similar cases in the literature.